I’m not sure what the best way is to say this, so I’ll just be direct. Big Pharma Sharma is going on an extended pause.

Starting this Monday (August 3rd), I am taking on a new senior leadership role at a publicly traded biotech company. You can keep an eye on my linkedin page to see where I am going and what I am doing. Unfortunately, given the scope of this role, it is going to be really difficult for BPS to co-exist with this new chapter in my career. There is just too much overlap and important ethical considerations. I also don’t feel like I can bring you the same level of objectivity and unvarnished analysis you’ve come to know. So the safest path here is for me to pause BPS. I think that is what is best for everyone at the moment. Whenever this new chapter is over, I’ll be back writing.

Logistically, what does this mean?

• If you’re a paid subscriber, I have paused future charges, so you will not be charged any additional subscription fees moving forward. You will still have access to all my past content.

• If you’re a yearly paid subscriber, please let me know if you would like a pro-rated refund. I’d be happy to do that for you. You’ll lose access to all my past content if you choose this path, but if a pro-rated refund is better suited for your situation, I’ll do that for you.

• Everyone else: you won’t be seeing any additional posts or updates from BPS for the time being.

Reflecting back on my multi-year newsletter journey that has taken me up to this point, I am still in shock about how much writing BPS has meant to me. I started this just as a way to stay engaged with the BioPharma community and provide a true insider’s perspective that I felt was missing from the broader discourse. It’s grown to be a true passion project. Something that brings me great joy to write every week. Something that has helped me refine my thinking and sharpen my perspectives. More importantly, the messages of support that I’ve received from many of you subscribers who I’ve never even met in-person, has meant the world to me. The fact that you’d be willing to pay me your hard earned dollars just to hear what some random guy on the internet has to say about BioPharma strategy, is still kind of crazy to me.

I’ll be back at some point, whenever this next chapter comes to a close. Until then, please don’t hesitate to reach out to me if you need anything. I can always be reached via email: shivu@bigpharmasharma.com

-BPS

Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

This week, Replimune scored a 10-3 AdComm win for RP1 in melanoma, Novo Nordisk watched its $2.8B IL-6 cardiovascular bet go down in a Phase 3 flame, and argenx dropped $2.2B to grab a CD122 antibody that could expand its immunology footprint well beyond VYVGART.

All that and more below. Let’s get into it!

📡 PRESS RELEASE DECODER

What the press releases actually mean

Novo Nordisk’s $2.8 Billion IL-6 Bet Fails in Phase 3 ZEUS: Ziltivekimab Cuts Inflammation but Does Not Cut Cardiovascular Events

📅 July 31, 2026 | 🏢 Novo Nordisk ( ) | 💊 ziltivekimab | 📋 Phase 3 Trial Failure (ZEUS)

Novo Nordisk announced July 31 that ziltivekimab missed the main goal of the Phase 3 ZEUS trial, failing to show it prevented heart attacks, strokes, or cardiovascular death in people with chronic kidney disease or atherosclerotic coronary artery disease. The drug did lower IL-6 and high-sensitivity C-reactive protein as expected, but those biomarker reductions did not translate into clinical event reduction. Novo’s shares fell as much as 10% on the news.

ZEUS enrolled more than 6,000 patients with elevated hsCRP levels who were randomized to ziltivekimab or placebo and followed for up to four years. The hypothesis was that blocking IL-6 would reduce hsCRP and thereby protect heart health, extending the logic of prior inflammatory cardiovascular trials including CANTOS with canakinumab. Novo gained ziltivekimab through its 2020 acquisition of Corvidia Therapeutics, for which it paid $725 million upfront with up to $2.1 billion in total payouts.

Novo said it will take a non-cash impairment charge in Q3 but will not need to change its operating profit guidance. Two other ziltivekimab trials, in heart failure and post-acute heart attack populations, are ongoing with results expected in 2027.

🧠 BPS Take: Ziltivekimab worked mechanistically, cutting both IL-6 and hsCRP, but that reduction did not translate to fewer deaths and heart attacks. This is the same question that has haunted the inflammatory cardiovascular hypothesis since the CANTOS trial showed canakinumab could reduce events but only at the cost of meaningful infection risk. What ZEUS hints at is that simply blocking a cytokine to reduce hsCRP isn’t good enough to reduce heart attacks. Or in other words, perhaps blunting the source of inflammation (e.g. lipids, plaques, etc.) is more important than blunting the inflammation itself.

The cardiovascular community will spend the next year arguing about whether the enrolled population was too late-stage, whether four years was long enough, or whether the IL-6 pathway is simply the wrong lever in these patients. The bigger casualty is the broader hsCRP-reduction thesis that several development-stage biotechs had been building on. BioAge’s 65% intraday drop tells you everything you need to know about how investors are repricing that mechanism risk today.

For Novo, this is painful but contained. The GLP-1 franchise generates enough cash to absorb a writedown without existential consequence. The two remaining ziltivekimab trials in different populations still run, but there shouldn’t be much weighing on those outcomes. They have been relatively quiet on the business development front, especially compared to Lilly, so perhaps the “clearing of the deck” of some of these internal programs could prompt Novo to be more aggressive in M&A.

Altimmune’s Pemvidutide Delivers Positive Phase 2 Data in Alcohol Use Disorder

📅 July 28, 2026 | 📊 Altimmune ( ) | 💊 pemvidutide | 📋 Phase 2 Trial Win (RECLAIM)

Altimmune reported positive topline results from the RECLAIM Phase 2 trial of pemvidutide, its once-weekly dual GLP-1/glucagon agonist, in alcohol use disorder (AUD). Pemvidutide 2.4 mg drove an average of 4.2 fewer heavy drinking days per week over 24 weeks vs. baseline, compared to a 2.75-day reduction on placebo — a statistically significant win on the primary endpoint. The drug also beat placebo on WHO Risk Drinking Level reduction, abstinent days, and delivered a 38% drop in serum phosphatidylethanol (vs. +5.9% for placebo), a direct biomarker of alcohol consumption. Safety was consistent with prior pemvidutide studies; five patients discontinued for GI-related AEs vs. zero on placebo. Altimmune plans to meet with FDA to discuss a pivotal path.

🧠 BPS Take: These data further validate the the therapeutic relevance of GLP-1 based mechanisms in curbing alcohol consumption. Lilly is probably quite pleased to see this positive signal in their competitors data, as they gear up for P3 data of brenipatide, the company’s once-monthly GLP-1/GIP agonist. It is still unclear how specific this anti-addiction effect is for GLP-1s. Do they simply down-regulate addictive behaviors broadly? Is this more a down-dialing of desire generally? Is this more a food-related/calorie-seeking effect, because alcohol is caloric like food is? All those questions will help elucidate how this aspect of GLP-1s work in the human mind.

For a longer take on brenipatide and why I think it may be the most impactful GLP-1 yet, see The GLP-1 You Probably Haven’t Heard Of.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

Replimune’s Three-Time Reject Beats the AdComm: RP1 Gets a 10-3 Vote and a Final Decision Date of August 2

📅 July 30, 2026 | 🏢 Replimune ($REPL) | 💊 RP1 (vusolimogene oderparepvec) plus nivolumab | 📋 FDA Advisory Committee Vote

The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted 10-3 on July 30 that efficacy results from Replimune’s IGNYTE study on RP1 combined with nivolumab are evaluable and clinically meaningful. The vote is non-binding, but the FDA is set to issue a decision by August 2 on a drug it has now rejected twice.

IGNYTE is a single-arm trial in patients with anti-PD-1-resistant advanced melanoma, a population where response rates to standard therapy are poor. Replimune reported an overall response rate of 33.6% in the full study population. FDA scientists pushed back hard in their briefing documents, arguing that when excluding patients without non-injected target lesions to assess systemic response, the ORR dropped to 15.7%. The agency’s concern is that the trial design made it difficult to distinguish RP1’s systemic effect from the local effect of direct tumor injection, and that deviations from RECIST v1.1 guidelines inflated the apparent response rate.

The majority of panelists disagreed. Hussein Tawbi of MD Anderson Cancer Center, voting in favor, said: “In my mind, this should be a therapy that’s available to patients in the short term until the Phase 3 trial reads out.” A confirmatory Phase 3 trial is expected to produce results in late 2027. Were the FDA to reject RP1 again, Replimune would need those results before making another submission.

Replimune’s resubmission reportedly came after White House intervention, a detail reported by the Wall Street Journal. The company had previously claimed a prior review team had found adequate evidence of efficacy, which the Makary-Prasad era FDA then reversed.

🧠 BPS Take: Well this Replimune story continues to be interesting. When the FDA flagged inconsistencies in the trial protocol and response measurement, it made it seem like Replimune was manipulating the data in their favor. That paired with a mudslinging PR campaign against the FDA gave me pause about RP1s chances. But this is exactly why adcoms are incredibly valuable. You have a major divide between the way the FDA sees RP1 and the way Replimune sees RP1. Convene a group of experts from diverse backgrounds to ask questions and provide their perspectives on what RP1s path should be and what value this new regimen could add for patients.

The Prasad-Makary era’s unwillingness to even have an adcom looks quite obstructive in retrospect. This was clearly a complicated case that required some public airing out. Is there evidence of abscopal effect? Does PD-1 retry in a post-PD-1 population work? Should RP1 have been used as monotherapy in the P2 design? What’s the correct way to measure response for an intratumoral therapy? The answers to those questions shouldn’t be set in stone by one person. It requires legitimate debate weighed against benefit-risk of this drug regimen for patients.

Holding this adcom so close to the PDUFA date is an odd one for sure. I would guess that the PDUFA date gets pushed back. Given the response discrepancy between the FDA and Replimune analysis, I have a really hard time seeing them come to terms about what goes into the label within a couple days. What that label looks like and how restrictive it is will influence RP1’s uptake (assuming it is approved) and how clean a launch they can have in the post-PD-1 setting. Given the FDA sees this as only a 15% ORR type of product, the Replimune on-label efficacy could look quite a bit smaller than the 33% the company is hoping for.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Argenx Pays $2.2 Billion for Forte’s FB102, Betting a Phase 1b CD122 Antibody

📅 July 27, 2026 | 🏢 Argenx ( ) | 💊 FB102 (anti-CD122 monoclonal antibody) | 📋 M&A Acquisition

Argenx agreed on July 27 to acquire Forte Biosciences for $77 per share in cash, representing a total equity value of approximately $2.2 billion. The deal reflects an approximately 86% premium to Forte’s volume-weighted average price since July 9, 2026, when Forte reported positive Phase 1b data in vitiligo. The transaction is funded entirely from argenx’s cash on hand, carries no financing condition, and is expected to close in Q3 2026.

The acquisition centers on FB102, a first-in-class anti-CD122 monoclonal antibody with clinical proof-of-concept in vitiligo and celiac disease. Phase 2 data in celiac disease is expected in the second half of 2026. Phase 1b data in alopecia areata is also expected in 2026. CD122 is a receptor subunit shared by the IL-2 and IL-15 receptor complexes, and blocking it modulates memory T cells that are implicated in multiple autoimmune conditions. Teva Pharmaceutical and First Tracks Biotherapeutics have similar drugs in clinical development.

Argenx had participated in a $150 million Forte stock offering in April 2026, signaling early interest. The company’s CEO Karen Massey described FB102 as aligning with “the argenx playbook: compelling biology, strong clinical validation and broad potential.” VYVGART, argenx’s anchor product, generated close to $2.9 billion in revenue in the first half of 2026 and already has approvals in myasthenia gravis and chronic inflammatory demyelinating polyneuropathy.

🧠 BPS Take: Don’t look now, but argenx is a $50B company with a major commercial engine in neuro-immune/inflammation. Bringing in the Forte asset builds on VYVGART’s commercial foundation and enables argenx to expand into new autoimmune areas like celiac and skin.

This acquisition continues a lengthening line of BioPharma middleweights becoming buyers of small biotechs. We have a growing set of companies that are commercial stage specialty players that are too big to be taken out by Big BioPharma. This group, headed by argenx, is now turning its attention outside its walls for R&D. Some other recent examples include Genmab x Merus - $8B, Biomarin x Amicus - $4.8B, Neurocrine x Soleno - $2.9B, and UCB x Candid & Neurona - $2.2B & $1.15B. I think we will see more names in this class (RevMed, Insmed, Jazz, etc.) become buyers over the next twelve months, competing with Big BioPharma for names in the sub-$8B-ish range. I am curious to see if names like Moderna and Alnylam also enter the fray, as their strategies are far more platform centric, thus limiting the pool of available target companies.

DISCLAIMER: Alright, legal department says I gotta say this: nothing in this post is financial, medical, legal, or any-other-kind-of advice. I’m just a guy on the internet with opinions, a penchant for clinical data, and an unhealthy obsession with BioPharma strategy. All views, opinions, and analyses are solely the work product of me and Big Pharma Sharma LLC — not my employer, clients, friends, associates, or anyone else who has ever been in the same meeting room as me. Do I have opinions on these companies, deals, and drugs? Obviously. Should you trade, invest, prescribe, or make life decisions based on them? Absolutely not. Manage your portfolio however you want, talk to actual licensed professionals, and please don’t hold me — or anyone adjacent to me — accountable when biotech does biotech things. You’ve been warned.

Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

This week, GSK cashed its first lung cancer chip from the $10.6B Nuvalent buy with an FDA approval for JIDEYTRO, Eli Lilly posts more pivotal retatrutide data but people are freaking out about the cardiovascular signal, and Novo Nordisk took Lilly to federal court over what it calls deceptive GLP-1 advertising.

All that and more below. Let’s get into it!

📡 PRESS RELEASE DECODER

What the press releases actually mean

GSK Gets Its First Lung Cancer Approval. The $10.6B Nuvalent Bet Just Started Paying Off.

📅 July 22, 2026 | 🏢 GSK ( ) | 💊 JIDEYTRO (zidesamtinib) | 📋 FDA Approval

The FDA approved JIDEYTRO (zidesamtinib) on July 22, 2026 for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer who have previously received a ROS1 kinase inhibitor. The approval is based on the ARROS-1 Phase 1/2 trial, which enrolled 117 patients and showed an objective response rate of 44% (95% CI: 34-53%), with duration of response rates of 82% at six months and 69% at twelve months.

This is GSK’s first approved medicine in lung cancer, and it comes directly from the Nuvalent, Inc. portfolio acquired through GSK’s $10.6 billion acquisition announced in June. The label is specifically for patients who have already progressed on a prior ROS1 inhibitor, which positions JIDEYTRO in a second-line-plus setting against drugs like crizotinib and lorlatinib that patients would typically receive first.

The approval was granted two-months faster than expected.

🧠 BPS Take: There was little doubt that this drug would get approved, which is a big reason why GSK forked over nearly $11B for Nuvalent. This initial approval is a first step in GSK’s commercial foray into NSCLC and will lay the groundwork for anticipated approvals of neladalkib (NVL-655) for patients with ALK-altered NSCLC, which is currently under FDA review with a target decision date of November 27th. ROS1 mutated NSCLC is a relatively small market, but early commercial experience enables physicians to get experience with JIDEYTRO ahead of 1L data readouts. It also helps GSK build relationships with lung cancer docs who would be prescribers of neladalkib in the much larger ALK+ NSCLC setting. Nuvalent was GSK’s largest acquisition ever and the approval of JIDEYTRO is the starting gun for the hard part of late stage acquisitions — ramping up the sales of the drug you just bought to meet all the revenue projections that went into your deal model.

Lilly Closes Out the TRIUMPH Program: 21% Weight Loss in Diabetes, 23% in Cardiovascular Disease, and a Q1 2027 BLA on the Calendar

📅 July 23, 2026 | 🏢 Eli Lilly ( ) | 💊 retatrutide (LY3437943) | 📋 Phase 3 Topline Data (TRIUMPH-2 + TRIUMPH-3) + BLA Filing Timeline

Eli Lilly announced on July 23, 2026, positive topline results from TRIUMPH-2 and TRIUMPH-3, two additional Phase 3 trials completing the TRIUMPH program for retatrutide. In TRIUMPH-2, adults with obesity or overweight and type 2 diabetes lost an average of 49.6 lbs (20.8%) at 80 weeks on the highest dose. In TRIUMPH-3, adults with severe obesity and established cardiovascular disease lost an average of 55.8 lbs (22.6%) at 80 weeks. Both trials met their primary endpoints.

These results complement the TRIUMPH-1 data released in May, where an all-comers obesity population achieved 30.3% weight loss at 104 weeks. The diabetic population (TRIUMPH-2) shows a weight loss ceiling that is lower than the all-comers number, which is consistent with what tirzepatide showed across its own program. The cardiovascular disease population (TRIUMPH-3) at 22.6% is competitive with what semaglutide showed in its SELECT trial population.

Notably in TRIUMPH-3 retatrutide showed a potentially negative cardiovascular signal when compared to placebo. There were 27 MACE-3 (cardiovascular death, heart attack, or stroke) events in participants randomized to retatrutide and 23 in those randomized to placebo, resulting in a hazard ratio of 1.12 (95.0% CI: 0.64 to 1.96). The study was not adequately powered to detect cardiovascular outcomes though.

Lilly plans to submit a Biologics License Application to the FDA in Q1 2027

🧠 BPS Take: The BLA designation instead of NDA is noteworthy here, as it would classify retatrutide as a biologic instead of a small molecule. This makes it eligible for more favorable exclusivity baseline before biosimilars can enter the market (12-years for biologics vs. 5-years for small molecule). If Lilly is able to pull this off it would also prevent compounders from being able to sell retatrutide whenever it launches, protecting it from the back-and-forth battle Lilly and Novo had with compounding pharmacies that marketed semaglutide and tirzepatide through tele-health channels. This is because under federal law, biological products approved under a BLA are entirely excluded from the statutory compounding exemptions that allow small-molecule chemical drugs to be duplicated during supply shortages.

The MACE signal here isn’t what you would like to see. Mechanistically GLP-1 and Glucagon agonism tend to increase resting heart rate. In a patient population that is already at higher CV risk, that doesn’t sound too great. However, I’ve seen way too many people get spun up about this as a definitive negative on retatrutide’s profile. Everyone in that camp needs to drink a can of “settle down juice”. Let’s remember this study wasn’t looking to measure CV outcomes. It looked at a few hundred patients over a short 80-week period. Even then, there was roughly 50 events that cropped up. One or two events swinging the other way and this would not be a story at all. CV outcomes trials are incredibly desired and prized for a reason. They are huge (often 10K patients) and are long, because it takes a while for sufficient number of cardiac events to accumulate in order to see a definitive signal. Semaglutide and other GLP-1s had similar stories where weight-loss focused studies showed neutral or numerically worse CV benefits, but when put to the true test in a CV outcomes study, they passed with flying colors. I am willing to bet the overwhelming weight loss patients are achieving with retatrutide will meaningfully outweigh any on-target heart rate increase and show a similar positive cardiac outcomes benefit as its predecessor GLP-1s have.

Vertex Was the Only Real Bidder for Crinetics

📅 August 4, 2026 (proxy filed) 🏢 Vertex ( ) acquiring Crinetics 💰 $85/share cash, ~$10B equity, 102% premium 📄 Proxy reveals Vertex was sole serious bidder; six other counterparties passed or capped at <$6B

The Crinetics proxy walks through the full deal timeline. Vertex first approached Crinetics on March 14 following a JPM26 meeting, submitted an initial $78/share bid on March 24 (rejected), and revised to $83 on April 19 (also rejected). Crinetics’s board, advised by Leerink and J.P. Morgan, canvassed six other potential acquirers. Three declined to engage, “Party A” concluded it could not exceed $6B and dropped out, and the final two also passed. Vertex moved to $84.50 on May 28, then landed at $85 on June 19 as its best-and-final. The board tried for $86 and got told no. Deal signed July 6.

🧠 BPS Take: One way to read this is that Vertex was bidding against itself, and Crinetics’ board did a good job extracting as much value as they could from Vertex, walking them up from $78 to $85 over three months.

Frankly, I am not that surprised that after the bank canvassed six other potential acquirers, none of them appeared all that interested. Pretty much all the other big acquirers aren’t in this rare-endocrine space and haven’t shown much attention towards it as of late. Crinetics also wasn’t some sexy buyout target prior to Vertex. To me, the play-by-play confirms that Vertex had deep conviction early on on the strategic fit of Crinetics and was committed to getting a deal done. The bank probably softly floated the opportunity out to other buyers to build leverage, but I doubt any found the same level of strategic fit or did the same depth of diligence as Vertex did. Vertex has nicely spread its bets across several relatively lower competition segments that (save for pain) command premium pricing — they’ve set themselves up to mostly play in spaces where the other big acquirers are largely absent. I really like that strategy for them.

These play-by-play proxy statements come out and everyone likes to overreact to the premiums when there was soft or little interest from other buyers. As we’ve discussed on BPS many times, none of that matters all that much in the grand scheme of things. The success or failure of this deal will depend on how well Vertex can commercialize these Crinetics assets — that’s the bulk of it. We’re not at the car lot haggling on the price of a used car, you know? We can Monday morning quarterback the premium all day if we wanted. But it really sounds like Crinetics was willing to go it alone, probably didn’t view themselves as a major takeout target, and when Vertex came along it forced them to think long and hard about what their takeout price should be. Just because you aren’t bidding against other buyers doesn’t mean your premium should immediately be lower. Maybe the seller never saw themselves selling until now.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

Novo Nordisk Takes Eli Lilly to Federal Court Over GLP-1 Ads

📅 July 21, 2026 | 🏢 Novo Nordisk ($NVO) vs. Eli Lilly ($LLY) | 💊 WEGOVY (semaglutide) vs. ZEPBOUND (tirzepatide) | 📋 Federal Lawsuit / Commercial Rivalry

Novo Nordisk filed suit against Eli Lilly in New Jersey District Court on July 21, 2026, alleging that Lilly has been running a nationwide pattern of deceptive advertising by comparing the highest doses of ZEPBOUND and MOUNJARO with lower doses of WEGOVY and OZEMPIC in commercial campaigns that ran during major sporting broadcasts and on TikTok and Facebook. John Kuckelman, Novo’s group general counsel, stated in an interview: “What has brought us to this moment is what we now see as a nationwide pattern, by Lilly, of deceptive advertising. They are intentionally confusing consumers.”

Novo brought its higher-dose 7.2 mg semaglutide to market in March 2026, achieving approximately 19% weight loss in clinical testing, but there has been no head-to-head trial comparing the highest dose of WEGOVY against ZEPBOUND. Lilly argues it is using results from the Surmount-5 head-to-head trial, which compared a lower dose of WEGOVY against ZEPBOUND and found 47% lower relative weight loss for the Novo product. Novo’s position is that those comparisons are now outdated given the availability of the higher-dose semaglutide. Novo is seeking a permanent injunction to pull the ads and require a corrective advertising campaign.

🧠 BPS Take: This lawsuit has some potentially damning reverberations for the sector if it goes Novo’s way. Novo is basically saying that Lilly needs to compare ZEPBOUND to high-dose WEGOVY, because that is where Novo’s data looks best now. This is despite the fact that there is no randomized study comparing ZEPBOUND to high-dose WEGOVY. So functionally, Novo is arguing that a cross-trial comparison is appropriate here, rather than the gold-standard in-trial comparison Lilly already did.

I am not a lawyer, but I think if Novo wins it sets a dangerous precedent. To be fair, Novo's legal angle isn't that SURMOUNT-5 is invalid, but that Lilly’s DTC ads obscure the dose details, making true data potentially deceptive under advertising law. The most likely outcome here is Lilly needing to use more specific language in its ads that more clearly and directly specify the WEGOVY dose ZEPBOUND was superior to.

Still, any company could “sue away” a competitor’s valid head-to-head study victory (for marketing purposes) if their drug later comes out with a higher dose that looks better. Taking that one step further, any company could “sue away” a competitor’s study data if their drug perhaps underperformed in that specific matchup relative to its historical best standalone readout. We already don’t see a ton of head-to-head studies between branded competitors due to the inherent commercial risk. This meaningfully diminishes the value of taking a head-to-head trial risk overall, other than if it is demanded by regulators for approval.

FDA AdCom Backs Six of Seven Compounded Peptides

📅 July 23–24, 2026 🏢 FDA Pharmacy Compounding Advisory Committee; HHS Secretary Robert F. Kennedy Jr. 📄 Six of seven peptides recommended for the 503A Bulks List (BPC-157, MOTS-c, KPV, TB-500, Epitalon, Semax); Emideltide voted down

The Compounding AdCom recommended six of seven peptides for the 503A Bulks List, opening a legal pathway for compounding pharmacies once rule-making completes. None have completed the human trials required for drug approval. FDA staff scientists recommended no votes across the board, citing absent human data, cancer and immune safety signals, and inconsistent chemical definitions. Eight new committee members were appointed pre-meeting, most with peptide industry ties.

🧠 BPS Take: Formalizing a compounding pathway for a gray-market problem is defensible. Right now there are thousands of people taking these peptides for various reasons from shady sources. My issue with all this is that the process to get here was so obviously hyper-political and not science-based. Using an AdCom stacked with peptide-industry members to grease the eventual legalization of these largely untested peptides just isn’t in the best interest of human health. Let’s run actual high quality studies and learn what these compounds do (good an bad) before making them easier to access.

GLP-1 compounders are a big winner from all this. As their ability to sell compounded GLP-1s diminish, a new opportunity to market peptides like BPC-157, TB-500, and MOTS-c for a number of largely unvalidated health benefits seems to be opening up. This is worse in a lot of ways than compounded GLP-1s. At least compounded GLP-1s had a reference product with legitimate clinical data. I worry that eventual misuse of these other peptides will lead to a lot of unfortunate and unforeseeable complications.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Sanofi Walks Away From Amlitelimab in Atopic Dermatitis. A Drug Once Billed as a Future Blockbuster Gets Quietly Shelved Under New Leadership.

📅 July 24, 2026 | 🏢 Sanofi ($SNY) | 💊 amlitelimab | 📋 Development Discontinuation

Sanofi announced on July 24, 2026, that it is discontinuing clinical development of amlitelimab, an OX40-ligand monoclonal antibody, in moderate-to-severe atopic dermatitis. The decision was made as part of an ongoing strategic assessment of the pipeline and will not include any submission for global regulatory review. The company stated that while the ESTUARY Phase 3 long-term extension study showed maintenance of clinical response and an emerging safety profile, amlitelimab “would not represent a meaningful improvement to the standard of care for patients with AD.” A Phase 2 study of amlitelimab in celiac disease remains ongoing and is expected to read out in the second half of 2026.

Amlitelimab was previously positioned by Sanofi as one of its most important pipeline assets in immunology, billed alongside DUPIXENT (dupilumab) as a next generation mechanism targeting OX40L rather than the IL-4/IL-13 pathway. The discontinuation represents a significant de-risking of the Sanofi pipeline narrative in atopic dermatitis, where AbbVie ($ABBV) recently acquired Apogee Therapeutics for $10.9 billion specifically to get ultra-long-acting dosing in the same indication. The decision comes during a broader pipeline review under Sanofi’s recently installed CEO.

🧠 BPS Take: “Would not represent a meaningful improvement to the standard of care” means the drug wasn’t differentiated enough to be of commercial value, plain and simple. I am more curious about how new CEO, Belen Garijo looks to reshape Sanofi’s pipeline. This really feels the like the first in a number of dominoes set to fall. Prior CEO, Paul Hudson, was dead set on making Sanofi a premium player in immunology and reducing dependence on their Regeneron-partnered portfolio. That vision never really came to pass. Is this the first step in a larger pull back for Sanofi across all of immunology or just a scalpel level cut? I would imagine the new CEO will hold a “strategy day” of some sorts in the coming months to paint her vision for the company. The big questions for me beyond how she sees the company’s commitment to immunology being defined is what new areas does she want to get into? Right now vaccines have been Sanofi’s most stable driver outside of its Regeneron-partnered assets, will there be a change in that TA?. I think Sanofi is in for quite a lot of changes over the second half of the year.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

DISCLAIMER: Alright, legal department says I gotta say this: nothing in this post is financial, medical, legal, or any-other-kind-of advice. I’m just a guy on the internet with opinions, a penchant for clinical data, and an unhealthy obsession with BioPharma strategy. All views, opinions, and analyses are solely the work product of me and Big Pharma Sharma LLC — not my employer, clients, friends, associates, or anyone else who has ever been in the same meeting room as me. Do I have opinions on these companies, deals, and drugs? Obviously. Should you trade, invest, prescribe, or make life decisions based on them? Absolutely not. Manage your portfolio however you want, talk to actual licensed professionals, and please don’t hold me — or anyone adjacent to me — accountable when biotech does biotech things. You’ve been warned.

Welcome back to Last Week Tonight in BioPharma (LWTB)!

This week: Merck gets the first oral PCSK9 inhibitor approved, Kalshi opens prediction markets for clinical trial outcomes, and Eli Lilly enters the psychedelics space with its acquisition of Atai Beckley.

All that and more below!

📡 PRESS RELEASE DECODER

What the press releases actually mean

Merck’s Enlicitide (LIPFENDRA) Wins FDA Approval as First Oral PCSK9

📅 July 15, 2026 🏢 Merck ( ) 💊 LIPFENDRA (enlicitide) 20 mg once-daily oral macrocyclic peptide PCSK9 inhibitor 📊 56% placebo-adjusted LDL-C reduction (CORALreef Lipids); 59% (CORALreef HeFH) 🔗 Merck press release | FDA announcement

FDA approved LIPFENDRA as the first oral PCSK9 inhibitor for adults with hypercholesterolemia, including HeFH, as an adjunct to diet and exercise. Approval is based on CORALreef Lipids and CORALreef HeFH, which delivered placebo-adjusted LDL-C reductions of 56% and 59% respectively at week 24 (both p<0.001), with parallel drops in ApoB and non-HDL-C. Safety was similar to placebo in the broader hypercholesterolemia population; HeFH patients saw higher rates of diarrhea (7% vs 2%) and dizziness (9% vs 4%). The cardiovascular outcomes trial, CORALreef Outcomes, has completed enrollment and is ongoing. MACE data is not yet available.

🧠 BPS Take: Called this one back in March when the Phase 3 hit at ACC26. Now that the approval is out of the way, the commercial challenge begins. LIPFENDRA enters into a market with three other approved PCSK9 inhibitors, all of which have underperformed relative to previous expectations. With the entrant of the first oral offering, we are about to find out why. Was underutilization of PCSK9 mostly driven by the on-market offering being injectibles? Was it less aggressive guidelines, which recently changed to more aggressively treat LDLc to lower target ranges?

My bet is the convenience advantage of an oral once daily pill, paired with an eventual cost parity (and maybe cost advantage) to injectables will quickly drive LIPFENDRA past REPATHA, the current market leader, which has only recently cleared $3B globally.

I wouldn’t sleep on the guideline shift being a major unlock for the entire lipid lowering class. More aggressive LDL targets should increase utilization of both generics (statins, ezetimibe) as well as PCSK9s, increasing the overall drug-treatable patient pool considerably.

RBC’s Brian Abrahams and UBS both peg peak sales around $5B, while Scotiabank’s Louise Chen sees “tens of billions” and Guggenheim sees a path above the $2.8B consensus. The buy-side range is quite wide, but you see a lot of “Bs” in those numbers and projections at a minimum that are on par with REPATHA’s best year.

The overhang is CV outcomes data. Amgen and Regeneron/Sanofi both had to run FOURIER and ODYSSEY OUTCOMES before payers meaningfully opened access. Merck could face the same hurdles, however it will be interesting to see how their formulary conversations go. The link between LDLc lowering and CV outcomes (to me at least) is already well established. If payers agree and Merck can offer better pricing, maybe LIPFENDRA can secure a favorable formulary position without it.

Biogen’s Diranersen Delivers Tau Signal in Alzheimer’s

📅 July 14, 2026 🏢 Biogen ( ), Ionis-partnered () 🧬 Diranersen (BIIB080), tau MAPT mRNA antisense oligonucleotide (ASO), intrathecal 📊 CELIA Phase 2: 26% CDR-SB slowing at 60mg; 50–65% CSF total tau reduction; tau PET reductions across brain regions 🔗 Biogen press release | AP coverage

Biogen presented full CELIA Phase 2 data at AAIC 2026 for diranersen, an intrathecal ASO targeting MAPT mRNA to reduce all tau isoforms. At 18 months, the 60 mg every-six-months arm (n=60) delivered a 26% slowing on CDR-SB (0.54 points), 42% on ADAS-Cog13, and 50% on MMSE versus placebo (n=115). CSF total tau dropped 50–65% across doses, with tau PET reductions across evaluated brain regions. CELIA missed its primary endpoint of dose-response on CDR-SB, since higher doses did not deliver greater benefit. ARIA is not anticipated with a tau mechanism. Biogen plans to advance to confirmatory Phase 3.

🧠 BPS Take: Kudos to Biogen for continuing to invest in Alzheimer’s research, especially with non beta-amyloid MOAs. This data brings some possibility that tau can be a therapeutically relevant target, and may also validate the growing view that amyloid was never going to be enough on its own.

That said, let’s not get ahead of ourselves. This is a Phase 2 with 60 patients in the best-performing arm and the drug did not show dose-response. The 60 mg arm outperforming both higher doses is a strange inverted dose curve that leaves confidence headed into Phase 3 a little bit lacking. AD is the proverbial graveyard of Phase 2 signals that did not replicate, from semagacestat to gantenerumab to a long line of tau vaccines and antibodies. Lecanemab and donanemab both hit their Phase 3 endpoints and barely moved the needle clinically.

For diranersen to be transformative, Biogen needs a large, well-powered Phase 3 in prodromal-to-mild AD that shows a clear cognition improvement. Intrathecal q6-month dosing is workable in a specialty neuro setting but is a real commercial constraint versus oral or subcutaneous. This fits the Biogen post-molt thesis, another anchor asset in a diversified late-stage pipeline, but AD requires Phase 3 confirmation to really feel confidence.

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When the outside world meets biopharma

Kalshi and AppliedXL Bring Prediction Markets to Clinical Trials

📅 July 17, 2026 🏢 Kalshi (regulated event exchange) partnering with AppliedXL (scientific intelligence platform) 📄 Pilot launches prediction market contracts on clinical trial outcomes and FDA approvals 🔗 AppliedXL partnership announcement | Kalshi biopharma markets

Kalshi is launching contracts on clinical trial outcomes and FDA drug approvals with AppliedXL as exclusive resolution partner. Each contract poses one binary question resolved against a pre-specified public document (ClinicalTrials.gov endpoint, FDA approval letter, AdCom vote record). AppliedXL detects the triggering event, extracts the outcome, has domain experts confirm it, and produces an audit trail. AppliedXL employees are prohibited from trading on prediction markets. AppliedXL is also launching Biopharma News, an AI-powered newsroom covering the same markets.

🧠 BPS Take: I wrote in April that prediction markets for clinical trials were prone to false precision, thin liquidity, MNPI abuse over long time horizons, and structural risks to trial enrollment and industry alignment. This sort of partnership and concerted effort to expand offerings in drug related markets is what I was worried about. Everything I said before still stands. What is worth acknowledging is that AppliedXL’s involvement does address one specific concern I raised, which is the accuracy and integrity of resolution. Pre-specifying the source document, using primary regulatory and clinical artifacts rather than press release spin, and building a defensible audit trail is a real improvement on the settlement side.

The problems I care about most, though, are upstream of resolution. Resolution integrity does not fix thin liquidity, and thin liquidity is what makes a $1,000 wager move the retatrutide market 40 percentage points. It does not solve MNPI, where 50 to 100 people at a sponsor, CRO, DSMB, or FDA touch directional signal for months before topline. It does not stop patients and referring physicians from anchoring on a “72% probability of success” as if it were an oracle. And it does not prevent the perverse-incentive scenario where insiders profit from failure. AppliedXL solving the “what happened” question does not solve the “who knew what when” question or the “does this warp enrollment” question.

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Deals, dollars, and what they signal

Lilly Acquires Atai Beckley for $2.8B, I Called It

📅 July 16, 2026 🏢 Eli Lilly ( ) acquiring Atai Beckley ( ) 💰 $6.75/share cash upfront (~$2.8B equity) + up to $2.50/share CVR (~$1.0B) 💊 BPL-003 (5-MeO-DMT intranasal) in Phase 3 for TRD; VLS-01 (DMT buccal film) Phase 2b; EMP-01 (R-MDMA) Phase 2 🔗 Lilly press release

Lilly is acquiring atai Beckley for $6.75 per share cash plus a $2.50 per share CVR tied to BPL-003 and VLS-01 development and regulatory milestones. Upfront equity is ~$2.8B, with up to ~$1.0B additional through the CVR. Lead asset BPL-003 (mebufotenin benzoate), an intranasal 5-MeO-DMT for treatment-resistant depression, has FDA Breakthrough Therapy Designation and Phase 3 initiated. In-clinic dosing runs ~2 hours per Phase 2b. Deal expected to close Q3.

🧠 BPS Take: Called this one in my predictions post at the beginning of the year. I flagged that at least one of Definium (formerly Mindmed) , Cybin, Compass, Attai, or GH Research was going to get taken out in 2026, and specifically pointed to major psychiatry players and Big Pharma as the logical acquirers. Lilly buying Atai Beckley fits that mold perfectly.

The broader read is that acquirer interest in psychedelics is real and building. The critique I hear most is that the in-clinic dosing model, REMS requirements, and specialty psychiatry training make these drugs commercially unworkable at scale. Look no further than J&J’s Spravato as the counter argument. Intranasal esketamine did $1.08B in 2024 and is projected around $1.7B in 2025 with ~57% YoY growth (and just posted a $585M quarter in Q2’26), with a network of certified treatment centers, payer coverage, and referring psychiatrist adoption that all had to be built from scratch. The infrastructure argument was fair for a time, but the work JNJ has done to build the rails can now enable others to run on them.

BPL-003’s ~2-hour in-clinic session is materially shorter than psilocybin’s 6-to-8-hour window, which is the real commercial differentiator over Compass and Definium if it holds up in Phase 3. Lilly gets a Phase 3 lead asset plus VLS-01 optionality plus a next-generation 5-HT2A discovery engine at a price that looks reasonable relative to SPRAVATO’s trajectory. Watch the other psychedelics names carefully over the rest of th year. Psychedelics is not a fringe category anymore and we should not be surprised if specialty psychiatry players or psych-curious Big Pharmas look at these names ass their entry point.

Alright, legal department says I gotta tell you. None of the above is financial advice. Please do your own due diligence. I am just a guy on the internet. Not a financial advisor.

Braveheart Files for IPO, Ticker BRVE

📅 July 14, 2026 🏢 Braveheart Bio filing S-1 on Nasdaq, ticker $BRVE (pending) 💊 BHB-1893, oral cardiac myosin inhibitor for oHCM and nHCM, licensed from Hengrui 📊 Phase 2 oHCM (n=42) showed rapid LVOT-G reduction; Phase 2 nHCM (n=84) improved diastolic function and cardiac biomarkers 🔗 FierceBiotech coverage | S-1 filing

Braveheart, led by former Hi-Bio CEO Travis Murdoch (who sold Hi-Bio to Biogen $BIIB in 2024 for $1.15B), filed to list on Nasdaq under ticker BRVE. The company licensed BHB-1893 from Jiangsu Hengrui in 2025 in a ~$1B biobuck deal with $65M upfront, followed by a $185M Series A led by a16z, Forbion, OrbiMed, Enavate, and Frazier. Phase 3 in oHCM starts H2 2026, nHCM in H1 2027. BHB-1893 will compete with BMS’s Camzyos and Cytokinetics’s $CYTK Myqorzo, both approved in oHCM.

🧠 BPS Take: The IPO window in cardiovascular-metabolic disease is way open, and Braveheart is the latest read on how wide. Kailera raised $625M in its IPO earlier this year on a similar Hengrui-licensed thesis in obesity. Kardigan priced an upsized $400M IPO at $16 in early 2026, and Scribe, Apnimed, and Attovia have all filed in the last two weeks. Capital is coming back to cardio and metabolic disease specifically because the exit math works. Cytokinetics’s trajectory post-aficamten approval and BMS’s willingness to pay $13B for MyoKardia in 2020 gave every investor a comp, and the China-in-licensing template is producing near-commercial assets at a fraction of the R&D cost of building from scratch.

BHB-1893’s competitive position is where it gets interesting. Camzyos missed its nHCM Phase 3 earlier this year, and Myqorzo showed a positive Phase 3 in nHCM in May, opening a real second indication for the class. Braveheart is arguing BHB-1893 has a differentiated PK profile that could sidestep the echo-monitoring burden that has slowed Camzyos and Myqorzo uptake. That could be a real commercial edge if the Phase 3 deilvers.

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Hasn’t it felt like there’s been a lot of deals this year? We’re only through about half the year and it certainly feels like it. Back in April, the folks at Stifel said we were tracking towards the second most active year in Biopharma M&A and since then it’s looked like it has already picked up quite a bit.

It’s good and healthy for there to be more deal activity. This has been paired with a growth in the number of buyers as well. Some were dormant and became rather active — particularly ex-US specialty pharmas, like UCB, Sun Pharma, Recordati, Ipsen, Otsuka, and Chiesi. Others make up the growing class of BioPharma “middleweights” who fit the criteria of being too big to be acquired easily by Biopharma heavyweights and are of a size and maturity where they too are ready to be buyers. Genmab made that transition this year with the acquisition of Merus. Neurocrine bought Soleno. Revolution Medicines has probably moved into this group as well. They join other names like Alnylam, BioMarin, and Argenx who could be selective buyers.

Still, it’s Big BioPharma that cuts the biggest and most checks. As their appetite goes so does the deal making.

With this year’s deal slew, one thing I found myself paying more attention to is how heavyweights say they intend to pay for these acquisitions. Typically, you’ll find a line or two tucked into the bottom of a press release or a follow-on SEC filing that explains whether a Big BioPharma intends to pay with cold, hard cash or a handful of elegant synonyms—like 'credit facility,' 'senior notes,' or 'commercial paper'—that are really just corporate speak for taking out a loan.

It’s easy to assume that the biggest companies in our sector are so flush with cash that they buy everything with cash. But that isn’t always the case. I started to see more companies take out debt to finance acquisitions. Some were taking out a little bit to supplement their cash. Others, like AbbVie with its recent acquisition of Apogee, just went ahead and financed the entire ~$9B with debt.

I figured if we can map out where, when, how, and who are debt users versus cash users, maybe we’ll get a better understanding of the acquisition “archetypes” of big biopharma players in our space. That’s effectively what I tried to do in this analysis. I looked at every big biopharma company acquisition from 2021 through 2026. I looked at whether they paid for the acquisition with just cash, just debt, or both. I tried to see if we get any interesting groupings that can shed light on particular acquirer archetypes. Who is more willing to take on new debt in order to do a big deal? Which companies are more hesitant to take on debt? And which ones are, for the most part, staying put unless they can acquire a company purely with cash?

Obviously, all of these companies are staffed with very talented financial professionals, and your treasury mix can shift based on a number of factors. It’s not to say that these archetypes are set in stone, but I think, as a supplement to understanding how “firepower,” or how large a company’s “war chest” is, understanding their finance mix as a style point to how they like to do acquisitions can shed light on who is a more realistic acquirer for particular buyout targets.

Why would a Big BioPharma company use debt at all?

So you might be thinking, “Isn’t it just better to pay with cash every single time? Why would a company ever even consider taking on debt to do an acquisition?”. And I think you’re not wrong to ask that question. I asked it to myself as well, and even as I’m writing this, I hear all the old school online personal finance gurus ( the Suze Ormans and Dave Ramseys of the world ) yelling at me for advocating for taking on more debt. But this is corporate finance, and that’s far different than personal finance.

Companies may look to take on debt for a few reasons. Adding debt gives them liquidity optionality, protecting their existing cash to be used for other things. Taking on debt also increases your ability to do a lot of deals very quickly. You don’t need to wait for your cash reserves to restock before you buy your next company. Just call the bank or issue some bonds and boom, there’s your firepower. And if you are a company with incredibly healthy cash flows, say someone like AbbVie, your capacity to take on more debt is a lot higher than someone without those healthy cash flows. All the money you’re bringing in means you have more ability to pay your interest payments. Additionally, debt can sometimes even be cheaper than cash in some respects. By funding an acquisition with low-cost debt, a company can actually lower its overall cost of capital, creating a tax shield that optimizes ROI for the deal. This is similar to how the interest on your mortgage is tax deductible. Debt, when at the right price and for the right acquisition, can be a really smart thing.

The trade-off to deploying debt so readily is that if you take on too much debt, your credit rating can go down, which signals an unhealthy underlying financial foundation for your company. In addition, paying the interest on that debt comes out as an expense, and therefore could suppress your earnings metrics. If you’re a centi-billionaire, this is how you avoid paying personal income taxes, but if you lean too hard into this as a corporation it starts looking like your business hates making money. There’s also a little added pressure for whatever you just bought to start adding to your cash flows and earnings sooner rather than later, because the bond holders of the bonds you issue carry coupon payments that can’t go missed. Miss them or reduce them and it starts to look like there are holes in your ship.

One way isn’t necessarily better than the other. Debt is always going to be available to the healthiest companies in our sector, even if you aren’t a frequent user of it. But by understanding how often a company is willing to take on debt to do small deals, medium-sized deals, large deals, or mega deals, we can get a better understanding of how they view their own buying power in the current environment.

Isn’t this just about size?

The mortgage example might’ve triggered a thought in your mind: the average person doesn’t have a boatload of cash lying around to buy a house, especially in the Bay Area, where I live. I guess unless you work for one of these AI companies, most of the time you’re looking to get a loan (i.e., a mortgage) to make a home purchase. So it stands to reason that Big Pharma would think similarly. Aren’t they just going to use debt more often when the deal size gets bigger? The bigger the deal, the less cash they have available to use, thus they’ll be more in need of tapping into debt.

And to that, I would tell you you are right. In the chart above, if you look at all of the Big BioPharma acquisitions in this analysis, which accounts for 123 total deals, and tier them out based on size, you see a clear pattern that the rate of deals requiring cash plus debt, or just debt alone, tends to increase as the deal size tier increases.

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Welcome back to Last Week Tonight in BioPharma (LWTB)!

This week: AstraZeneca and Ionis see disappointing results in ATTR Cardiomyopathy, Vera sees accelerated approval of TRUTAKNA ahead of eGFR data in Q3, the FDA pauses CRLs but then restarts them, and Vertex acquires Crinetics for nearly $10B.

All that and more below!

📡 PRESS RELEASE DECODER

What the press releases actually mean

AstraZeneca and Ionis WAINUA Misses in CARDIO-TTRansform ATTR-CM

📅 July 9, 2026 | 🏢 AstraZeneca (AZN),IonisPharmaceuticals(IONS) | 💊 Wainua (eplontersen), TTR antisense silencer | 🏷 Phase 3 Failure / ATTR-CM | 🔗 Ionis press release, FiercePharma, Alnylam Q1 2026 results, FiercePharma on ATTRUBY

WAINUA missed the primary endpoint in CARDIO-TTRansform (n=1,432, largest ATTR-CM trial ever run), a composite of CV mortality and recurrent CV events through Week 140 versus placebo on top of standard of care. In a pre-specified subgroup of patients on eplontersen monotherapy without a stabilizer at baseline, the hazard ratio was a nominally significant 0.71. In patients already on a stabilizer, no treatment effect was observed. 57% of patients in each arm were on a stabilizer at baseline and another 24% initiated one during the trial. WAINUA produced large sustained TTR reductions, safety was clean, and multiple secondary imaging and biomarker endpoints favored eplontersen. AZN shares fell around 7% and IONS around 21% on the news. Full data will be presented at ESC Congress August 2026. Wainua remains approved and marketed in ATTRv-PN in 20-plus countries.

🧠 BPS Take: Ionis CEO Brett Monia attributed the miss to the rapidly evolving treatment landscape in ATTR-CM. When CARDIO-TTRansform started enrolling, ATTR-CM patients were not universally on tafamidis. By the time the trial read out, 81% of participants were either on a stabilizer at baseline or initiated one during the study. Basically, adding a TTR silencer on top a stabilizer didn’t add any benefit. The monotherapy subgroup hazard ratio of 0.71 tells you the drug is probably working when it isn’t competing with a background stabilizer drug that is already lowering TTR levels upstream.

BridgeBio’s ATTRUBY (acoramidis) feels like the real winner here. Ionis’ study is evidence that combination therapy doesn’t add value, and that the stabilizer MOA is a powerful therapeutic anchor as a monotherapy. It looks to be comparatively better than Pfizer’s VYNDAMAX, which is a first-generation stabilizer. ATTRUBY put up $37M in its first full quarter and just closed a $1B Sixth Street and KKR preferred equity raise last week that I covered in depth.

Alnylam’s AMVUTTRA generated $889.9M in Q1 2026, up 187% year over year and the stock price rallied a bit on this news. AMVUTTRA has its own positive HELIOS-B data supporting the silencer approach, but there was far less background stabilizer use when that study ran. Payers now have evidence to point to to say they’d rather have patients on a stabilizer first before moving to a silencer.

This also puts added pressure on the development of Alnylam’s next-gen silencer, nucinersen. Alnylam is moving nucresiran into a pivotal Phase 3 trial called TRITON-CM to test it in cardiomyopathy. The problem? In 2026, finding a newly diagnosed ATTR-CM patient who isn't already taking a stabilizer is incredibly difficult. And nucinersen is probably the drug Alnylam wants to quickly overtake Amvuttra, as the companies owed double-digit royalties to Blackstone on sales of Amvuttra, thus compressing its margin.

Vera Therapeutics TRUTAKNA Wins FDA Accelerated Approval. Seventh IgAN Drug, First Dual BAFF/APRIL Inhibitor Enters a Competitive Nephrology Market

📅 July 7, 2026 | 🏢 Vera Therapeutics ( ) | 💊 TRUTAKNA (atacicept-vymj), dual BAFF/APRIL inhibitor | 🏷 FDA Accelerated Approval / IgA Nephropathy | 🔗 Vera press release, BioSpace, NEJM ORIGIN 3

The FDA granted accelerated approval to TRUTAKNA for adults with primary IgA nephropathy at risk of disease progression, based on ORIGIN 3 Phase 3 data showing a 46% reduction from baseline in proteinuria (24-hour urine protein-to-creatinine ratio) at Week 36 versus placebo. Dose is 150 mg subcutaneous weekly, self-administered. Full approval is contingent on eGFR data at Week 104 as the confirmatory endpoint. TRUTAKNA is the first B-cell modulator targeting both BAFF and APRIL to reach the market. The approved IgAN armamentarium now includes Tarpeyo (Calliditas), Filspari (Travere ), FABHALTA and VANRAFIA (Novartis, ), VOXYACT (Otsuka), and now TRUTAKNA. Vera has already begun launch execution.

🧠 BPS Take: IgAN went from an unmet-need orphan indication five years ago to a multi-drug commercial slugfest in 2026. How each drug differentiates from its competitors and what patients they aim to compete for will be key to monitor as this market matures. For Vera and TRUTAKNA that main competitor is Otsuka’s VOXYACT, an anti-APRIL mAb. TRUTAKNA’s label looks pretty clean relative to VOXYACT, with broader patient eligibility language and no prominent warnings for neutralizing antibodies.

The real tests will come in the second half of the year once both drugs’ long-term eGFR numbers are made available for cross trial comparison. Otsuka already reported “significant stabilization and improvement in annualized eGFR slope”, leaving the field waiting for specific numbers to be reported at an upcoming conference. Vera has moved up its eGFR data readout to Q3 2026. Numerically stronger numbers should drive TRUTAKNA’s commercial uptake significantly and support a smooth sBLA filing (expected Q4’26) to convert the accelerated approval into a full approval.

Lurking around the corner is Vertex, which has a PDUFA date for its own BAFF/APRIL inhibitor, povetacicept on November 30th, 2026. Povetacicept looked numerically better than TRUTAKNA on UPCR change, the main surrogate endpoint for accelerated approval. If TRUTAKNA looks better than VOXYACT on eGFR, that starts to speak to a potential advantage dual BAFF/APRIL inhibition has over single target inhibition. It also may raise physicians expectations for povetacicept’s eGFR results since it registered a numerically higher UPCR change than TRUTAKNA. We won’t know the full eGFR numbers for Vertex until 2027, but that perception is something Vera may have to contend with if they achieve the eGFR numbers they are hoping for.

Kailera and Hengrui HRS-7535 Oral GLP-1 Delivers 10.9% Weight Loss in Chinese Phase 3. 70% Nausea Rate Is the Story

📅 July 7-8, 2026 | 🏢 Kailera Therapeutics (private), Jiangsu Hengrui Pharmaceuticals | 💊 HRS-7535, oral small-molecule GLP-1 receptor agonist | 🏷 Phase 3 Topline / China | 🔗 Kailera press release, FierceBiotech, BioPharma Dive

Hengrui reported topline data from two Phase 3 China trials of HRS-7535 in obesity/overweight and Type 2 diabetes. In the obesity trial, mean weight loss at Week 44 was 10.9% at the 180 mg dose and 9.8% at 120 mg. Both doses hit primary endpoints. Nausea was reported in 70.3% of patients on 120 mg and 70.0% on 180 mg versus 16.2% on placebo. Discontinuation rate not broken out at topline. Kailera holds ex-China rights via the 2024 Hengrui licensing deal, was co-founded by Atlas Venture and Bain Capital, and is running a parallel US development program. Kailera stock dropped approximately 10% on the release.

🧠 BPS Take: 10.9% weight loss with an oral small molecule is a solid result and puts HRS-7535 in the same efficacy neighborhood as oral semaglutide at higher doses and Lilly’s orforglipron. The nausea number is the problem.

Orforglipron ATTAIN-1 reported nausea rates in the mid-30s at the highest dose with a well-managed titration schedule. A 70% nausea rate is not competitive with what the field has already established as a manageable tolerability profile. If those numbers hold in western studies with KAI-7535, it doesn’t bode for a competitive profile. Perhaps Kailera looks to explore a more aggressive titration schedule to blunt the GI side effects, but that too comes with the trade off of time, cost, and inconvenience.

This readout doesn’t totally nuke the thesis behind Kailera’s massive IPO earlier in the year. They have multiple assets in P2 and P3 studies for obesity. If they don’t see a viable path to making KAI-7535 commercial competitive, they can easily pivot to one of their three other clinical stage programs.

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When the outside world meets biopharma

FDA’s CRL Transparency Push Wobbles, Then Doesn’t

📅 July 10-11, 2026 🏢 FDA / HHS, Acting Commissioner Kyle Diamantas 📄 Policy pause reversed within days after 16 new CRLs released 🔗 FierceBiotech | BioCentury | Proposed rule

FDA quietly paused real-time release of Complete Response Letters in April after a Covington & Burling citizen’s petition on behalf of an undisclosed pharma company challenged the policy over unredacted confidential information. The petition cited specific unredacted material in the Lykos and Stealth BioTherapeutics CRLs. Days after the pause was reported, FDA released 16 new CRLs, including the Hengrui/Elevar camrelizumab plus rivoceranib rejection. HHS is simultaneously advancing a proposed rule to eliminate the presumption that a marketing application’s existence is confidential commercial information.

🧠 BPS Take: Marty Makary’s tenure will not be remembered fondly, but CRL transparency was the one policy he championed that the industry should actively want to keep. CRL transparency can help drive learning that leads to more successful FDA submissions — i.e not repeating mistakes others have made and also getting a clearer sense of regulatory precedent and expectation.

The right posture for Big Pharma is to support codification with sensible guardrails, sponsor pre-review of redactions, a short embargo window to prepare a response, and clear standards for what stays confidential. Fighting the policy outright is a losing PR fight, but I guess you could argue Big Pharma has nothing to lose on the PR front. Getting behind it and shaping the redaction rules is the move that protects trade secrets and builds trust at the same time.

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Deals, dollars, and what they signal

Vertex Pays $10B for Crinetics. Endocrinology Becomes the Fifth Vertex Pillar, but the 102% Premium Is the Story

📅 July 6, 2026 | 🏢 Vertex Pharmaceuticals (VRTX), Crinetics (CRNX) | 💊 Palsonify (paltusotine, oral acromegaly), atumelnant (CAH/Cushing’s, Phase 3) | 🏷 M&A / Endocrinology| 🔗 BioPharma Dive, BioWorld, Reuters

Vertex agreed to acquire Crinetics for $85 per share in cash, $10B equity value and approximately $8.8B net of cash. This is Vertex’s largest deal ever. The premium is 102% to Crinetics’ pre-deal price, second only to the Biogen/Apellis 140% premium among 2026 buyouts. Closes Q3 2026. PALSONIFY (paltusotine), an oral once-daily somatostatin analog for acromegaly, was FDA-approved September 2025 and generated $10M in Q1 2026, beating consensus in its first full quarter of launch. Atumelnant is a Phase 3 oral ACTH receptor antagonist for congenital adrenal hyperplasia and Cushing’s syndrome. Vertex claims combined peak sales potential of $5B-plus. Endocrinology becomes Vertex’s fifth therapeutic pillar alongside cystic fibrosis, sickle cell/beta-thalassemia (CASGEVY), pain (JOURNAVX), and kidney disease (povetacicept, PDUFA November 2026).

🧠 BPS Take: Vertex has been gradually building the “other legs of the stool” so to speak, to diversify beyond its seemingly impenetrable moat in Cystic Fibrosis. With their biggest acquisition, ever, what the other legs of the stool are have come into clear view: cystic fibrosis, non-malignant hematology, pain, rare renal, and now with the addition of Crinetics — endocrine. You don’t see any oncology, obesity, IBD, derm-immunology, or rheumatology on that list. Vertex has nicely spread its bets across several relatively lower competition segments that (save for pain) command premium pricing. IgAN as I mentioned before is going to be a war zone, but pain has been a graveyard for Pharma for decades. And CF will always attract challengers, but Vertex has long-seemed to have the magic formula in that space. Now adding endocrine to the mix, and Vertex all of a sudden looks like the king of the jungle in this space largely competing against specialty players like Neurocrine, Ipsen, and Ascendis.

Outside of CF though, Vertex’s other approved products, particularly CASGEVY and JOURNAVX have been slow to turn into commercial growth engines. CASGEVY launch has been notoriously slow, with heavy friction throughout the patient journey with it taking anywhere between 6 to 9 months for Vertex to recognize revenue. JOURNAVX has also been slow to ramp, not due to a lack of demand, but due to mainly seeing resistance with commercial access and pricing relative low-cost generic opioids. These are still really good products, but the commercial launch expectations were perhaps too aggressive. It will take time.

The 102% premium has some sticker shock built into it, but all that won’t mean much if PALSONIFY and atumelnant achieve blockbuster status. The upside case rests on atumelnant in CAH. Neurocrine’s ( ) CRENESSITY sets a high safety bar and is a strong market incumbent, however Phase 2 data for atumelnant suggests a once-daily profile that avoids strict food restrictions and offers superior efficacy by way of absolute biomarker normalization and increased steroid sparing, alongside a massive secondary expansion runway in Cushing's.

Novartis Pays $1.1B Upfront for Myricx Bio’s Preclinical ADC Payload Platform

📅 July 6, 2026 🏢 Novartis ($NVS) acquiring Myricx Bio (private, UK-based) 💰 $1.1B upfront, up to $400M in milestones ($1.5B total) 🧬 NMTi ADC payload platform, two lead assets against B7-H3 and HER2 | 🔗 Novartis press release | BioWorld coverage | GEN coverage

Novartis $NVS agreed to acquire UK-based Myricx Bio for $1.1 billion upfront and up to $400 million in milestones, with close targeted for H2 2026. Myricx is preclinical. What Novartis is buying is a payload platform built around N-myristoyltransferase inhibitors (NMTi), a mechanism distinct from the topoisomerase-1 payloads (deruxtecan and its variants) that anchor the current ADC leaderboard, plus two lead programs directed against B7-H3 and HER2. Fiona Marshall, President of Biomedical Research at Novartis, framed the deal around addressing “limitations of commonly used ADC payload classes such as TOPO-1 inhibitors” in the company statement.

🧠 BPS Take: To me, the main reason that explains why Novartis is choosing to pull the trigger now is payload differentiation. The ADC space has consolidated around Dxd chemistry, from Enhertu through datopotamab deruxtecan through the wave of TROP2 and B7-H3 assets in development at Daiichi Sankyo, Merck, AstraZeneca, and a lot of China ADCs that have been licensed by the west over the last two years. Payload resistance is the emerging bottleneck. Novartis is saying it wants a payload that works in TOPO-1 resistant models, which is a real clinical problem in patients cycling through multiple ADCs sequentially. NMT inhibition disrupts protein lipidation across broad substrate classes rather than triggering DNA damage, so the mechanistic case for non-cross-resistance is credible on paper.

Clinical validation is the major big hanging outstanding question. $1.1 billion upfront for a preclinical platform is aggressive by any historical benchmark, and the milestone tail of $400 million is unusually small relative to the upfront, which tells you Myricx negotiated hard on cash certainty over biobucks. Clinical data will tell us whether this was an impulse buy or a savvy bet to shape the future of ADCs.

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Welcome back to Last Week Tonight in BioPharma (LWTB). Hope you had an enjoyable Fourth of July weekend. LWTB is here to catch you up on what you missed while you were away.

Roche’s divarasib became the latest RAS inhibitor to register impressive data (this time in NSCLC). Your favorite chatbot, Claude, became your competitor overnight, with Anthropic announcing that its new “Claude Science” offering will also be leveraged by the company to develop its own therapeutics. Plus, Euro-midcap Ipsen unloads $2.5B in M&A dollars in just three days.

All that and a couple more below!

📡 PRESS RELEASE DECODER

What the press releases actually mean

Roche’s Divarasib Beats Lumakras and Adagrasib Head-to-Head in Phase 3 KRAS G12C NSCLC — Third-to-Market With Best-in-Class Data

📅 July 1, 2026 | 🏢 Roche / Genentech (RHHBY),Amgen(AMGN), Bristol Myers Squibb (BMY),RevolutionMedicines(RVMD) | 💊 divarasib (GDC-6036) vs sotorasib (Lumakras) and adagrasib (Krazati) | 🏷 Phase 3 Readout / KRAS / Second-Line NSCLC

Genentech reported that Krascendo-1 (NCT06497556, n=338), the global head-to-head Phase 3 trial of a KRAS G12C inhibitor against the two approved incumbents, hit both its primary and key secondary endpoints. Divarasib delivered statistically significant and clinically meaningful improvements in progression-free survival versus sotorasib or adagrasib, and hit overall survival at the interim analysis. Discrete efficacy numbers have not been disclosed and will come at an upcoming medical meeting. No new safety signals; the safety profile was consistent with prior divarasib data. The trial excluded patients who had previously received a KRAS G12C or pan-KRAS/RAS inhibitor.

Roche plans to submit divarasib for approval in second-line NSCLC in 2027, per its recently disclosed regulatory submission list. Roche has guided peak divarasib sales of CHF 1–2 billion (~$1.2–2.5B), a range Jefferies analysts have echoed for the 2L opportunity alone. Divarasib holds FDA Breakthrough Therapy Designation (2022) and Orphan Drug Designation (2026) in KRAS G12C NSCLC.

Two additional Phase 3 trials are ongoing: Krascendo-2 (divarasib + pembrolizumab vs chemo + pembro in 1L advanced KRAS G12C NSCLC, NCT06793215) and Krascendo-3 (adjuvant divarasib monotherapy vs immunotherapy or observation in resected stage II–IIIB KRAS G12C NSCLC, NCT07541170).

🧠 BPS Take: Lumakras was FDA-approved in 2021, Krazati in 2022. Full-year 2025 sales were ~$368M and ~$240M respectively — both meaningfully below launch-era analyst expectations. History says me-better targeted oncology drugs with better data tend to supplant incumbents. Osimertinib entered EGFR behind gefitinib and erlotinib, then moved to first-line and now generates >$6B/year while the first-gen agents lag behind. Alectinib entered ALK behind crizotinib and now holds roughly 60% of the market. Lorlatinib is doing the same to alectinib in CROWN. In molecularly defined NSCLC oncologists switch fast when the OS data shows there is a better drug available.

Divarasib fits that template cleanly. It won on OS in a head-to-head study against existing KRAS G12C inhibitors. Lumakras and Krazati are modestly successful commercial products, but have certainly never achieved the scope and scale once expected of them when they first launched and would seem to be easily displaced.

Two things worth watching before the read-throughs get overdone. First, the actual PFS and OS deltas — “statistically significant” at interim doesn’t tell you whether this is a 2-month or 6-month OS improvement. The absolute magnitude will dictate how easily divarasib displaces Lumakras and Krazati. Second, Krascendo-2 in first-line is where the CHF 2B high case lives; second-line is a $500M–$1B franchise on its own.

AstraZeneca’s Strensiq Successor Efzimfotase Alfa Hits Pediatric MULBERRY but Misses Adult HICKORY — Franchise Succession Story Now Depends on Salvaging the Bigger Half of the Market

📅 June 28-29, 2026 (ICCBH Montreal) | 🏢 AstraZeneca ($AZN) / Alexion | 💊 efzimfotase alfa (ALXN1850) vs. Strensiq (asfotase alfa) | 🏷 Phase 3 Full Data / Hypophosphatasia (HPP)

AZN presented full data at ICCBH from three Phase 3 trials of efzimfotase alfa, a Q2-week SC enzyme replacement therapy versus Strensiq’s 3-6x weekly dosing.

MULBERRY (pediatric naïve, n=29): Hit primary. RGI-C bone score median difference 1.67 vs placebo (p=0.0003); RSS median difference -1.00 (p=0.0008). CHESTNUT (pediatric switchers, n=43): Bone health maintained; comparable TEAE rate. HICKORY (adolescent/adult naïve, n=124): Missed primary — 6MWT no better than placebo. AZN attributed the miss to strong placebo performance and reported nominal significance in the pediatric-onset subgroup.

Safety: ISR rate 5x lower than Strensiq registrational trials; 98.8% ISR-free days. Commercial: Strensiq 2025 sales $1.7B. AZN peak guidance $3-5B, contingent on adult expansion (~80% of HPP TAM). Manufacturing cost “way under” Strensiq per CEO Marc Dunoyer. Strensiq US patent expiry ~2028, EU 2032. Regulatory filings planned; no BLA date confirmed.

🧠 BPS Take: This isn’t the readout AZN needed. Efzimfotase alfa was designed to grow a $1.7B franchise to $3-5B on the back of adult expansion, and HICKORY missed. Parsing the data in these sorts of rare diseases goes over much easier with regulators than in larger indications, so AZN will still push to get adults on the approved label, and the pediatric-onset subgroup nominal significance gives them the argument to make. How successful this effort is will determine whether this franchise stays in the $2B range or starts to move up to the $3-5B projections.

Strensiq’s 2028 US patent cliff means AZN has to defend or replace regardless, Q2-week dosing is a patient-experience win versus 3-6x weekly injections, lower manufacturing cost helps margin and formulary negotiations, and CHESTNUT means AZN can hold the pediatric base while payer contracts reset. This is a real defense against the most near-term threat, which is post-2028 biosimilar Strensiq. Novel competitor drugs are still in early stage and ways away from approval.

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When the outside world meets biopharma

Anthropic Launches Claude Science and Announces Its Own Drug Programs for Rare and Neglected Diseases

📅 June 19, 2026 (Jumper hire) & July 1, 2026 (Claude Science launch) | 🏢 Anthropic (private, pre-IPO); | 💊 Undisclosed rare/neglected disease programs; PKU shown as demo | 🏷 AI / Platform / Strategic Positioning

At an event for pharma executives, biotech founders, and researchers on Tuesday, Anthropic launched Claude Science, positioned alongside Claude Code and Claude Cowork as a third flagship product. It integrates 60+ curated skills across genomics, single-cell, proteomics, structural biology, and cheminformatics; runs on the researcher’s own HPC or laptop; connects natively to NVIDIA BioNeMo (Evo 2, Boltz-2, OpenFold3); generates reproducible figures and manuscripts with auditable code trails; and includes a reviewer agent that checks citations and calculations. Beta live for all paid Claude subscribers.

At the same event, Anthropic announced explicitly that it will use Claude Science to pursue its own drug candidates for rare and neglected diseases. Eric Kauderer-Abrams, Anthropic’s head of life sciences, framed drug discovery as central to the company’s mission, stating: “Our mission is to develop AI that serves humanity’s long-term well-being, and we believe that by far the greatest opportunity to do that is in the life sciences.” Alexander Tarashansky, who led Claude Science’s development, demonstrated the system autonomously identifying drug candidates for phenylketonuria (PKU) live on stage. Kauderer-Abrams previously told CNBC in October that Anthropic wants “a meaningful percentage of all of the life science work in the world to run on Claude, in the same way that that happens today with coding.”

Anthropic’s paid pharma customer base already includes BMS (Claude deployed to 30,000+ employees), Sanofi (workforce-wide), Novo Nordisk (NovoScribe CSR automation), and named partnerships across most of the top 15 pharmas. The company is approaching its first profitable quarter with an IPO expected later this year.

🧠 BPS Take: When I mapped 27 frontier-AI/Pharma partnerships in May, I put Anthropic in the “science partner” bucket because the context window handles 200-page protocols and the safety/compliance posture sells cleanly into a regulated industry. The expanded Claude Science toolkit can certainly be a major value add for drug developers and enables Claude to integrate more deeply with its BioPharma customers.

What I did not expect this soon was Anthropic explicitly announcing that it will be developing its own drug programs. Anthropic’s interest in doing its own biology work was clear two months ago when they bought Coefficient Bio, a sub-ten-person stealth AI biotech founded in 2025, for $400M in stock. Its founding team came from Genentech’s Prescient Design (Nathan Frey, Samuel Stanton), Evozyne (CEO Aris Theologis), and Roivant (Joyce Hong)— basically an acquihire play. Then on June 19th they hired John Jumper, nobel laureate who co-created AlphaFold with DeepMind’s Sir Demis Hassabis. This Claude Science unveil is step three.

Now it remains unclear what this means in terms of commitment level. Are they simply discovering new programs and will license them out to more experienced players to take them the rest of the way? Are they going to develop them completely themselves? Will they just focus on neglected disease or will they expand into more competitive areas? Does Anthropic see itself as just the service/enablement layer in drug development or do they really want to go so far as to commercialize their own drugs?

The neglected-disease framing is smart positioning to start frankly: humanitarian cover, low regulatory scrutiny, no/low direct conflict with any named customer’s asset. Anthropic can even spin the drug unit out as its own rare disease focused biotech, perhaps even as a public benefit corporation or other less capitalist sounding structure. Focus on the thousands of ultra rare diseases with high unmet need but challenging economics, and do this all as a “gift to society” while serving as a demo of Claude Science in the process. If it fails to do anything, then they can let it die on the vine and they still have the underlying service layer with all their pharma partners keeping them in the fold on AI for drug development. If it succeeds, it is true end-to-end proof of Claude Science’s benefit.

For biopharma customers this creates “coopetition” with information asymmetry. Your AI vendor could now be reading across your enterprise data and workflows, arming itself and its pipeline to compete with you down the road. Certainly Anthropic will say that firewalls will be in place and that they would never use a client’s secure data, but we’ve seen tech companies go back on that promise many times before. If you’re integrated with the Anthropic suite now, you have to think critically about how you protect your data, workflows, and internal knowledge. Perhaps GSKs decision to build their own AI capabilities from the ground up, vs partnering with one of the major labs, looks like a smarter decision in retrospect.

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💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Ipsen Spends ~$2.5B in Biobucks Across Two Deals in Three Days — Kartos ($450M Upfront) for Myelofibrosis, Memo ($227M Upfront) for BK Virus in Kidney Transplant

📅 June 27 & June 29, 2026 | 🏢 Ipsen ($IPSEY), Kartos Therapeutics (private), Memo Therapeutics (private) | 💊 navtemadlin (oral MDM2 inhibitor); potravitug (anti-BK polyomavirus mAb) | 🏷 M&A / Late-Stage Oncology + Rare Disease

Ipsen announced two acquisitions in three business days. Kartos (June 27):$450M upfront + up to $1.3B in regulatory and sales milestones. Adds navtemadlin, an oral MDM2 inhibitor being run in the global Phase 3 POIESIS trial (>600 patients, >250 sites) as add-on to ruxolitinib in intermediate/high-risk TP53wt myelofibrosis patients with suboptimal ruxolitinib response. Top-line data expected 2027; potential launch 2028. Prior Phase 1b/2 (n=19 suboptimal responders) showed 42% ≥25% SVR, 32% ≥35% SVR, 32% TSS50, and disease-modifying signals (71% ≥20% VAF reduction, 57% BMF improvement by Grade ≥1).

Memo (June 29): €200M (~$227M) upfront + >€500M in milestones. Adds potravitug, a first-in-class anti-BK polyomavirus antibody entering pivotal Phase 2/3 later this year in kidney transplant patients with BK virus-associated nephropathy. FDA fast-track and EU orphan designations. Close expected Q3 2026 for both. Ipsen’s 2025 revenue mix: €2.5B oncology, €747M neuroscience, €384M rare disease.

🧠 BPS Take: Two deals in three days from a mid-cap European specialty pharma is a statement of intent, and the deals are internally consistent with Ipsen’s stated three-pillar strategy (oncology, rare, neuro). But the Kartos deal is the more interesting one and it deserves scrutiny.

I wrote about the myelofibrosis landscape in May and flagged navtemadlin as the more credible of the two MDM2 programs left standing. Kartos smartly re-designed POIESIS to enroll suboptimal ruxolitinib responders after the JAK-refractory BOREAS study delivered mixed results. Phase 1b/2 subset showed a disease-modifying signal in a class that has struggled to show anything beyond spleen shrinkage, so Ipsen is seemingly buying a real drug here. I just question whether $450M upfront and $1.75B all-in for an asset with a 2028 potential launch, in a market where Incyte’s Jakafi generic entry hits December 2028 and CALR-directed antibodies from Incyte and J&J are moving toward Phase 3 is worth it.

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BridgeBio Raises $1 Billion in Preferred Equity From Sixth Street and KKR: A Sophisticated Capital Markets Move That Is Not a Distress Financing

📅 July 1, 2026 | 🏢 BridgeBio Pharma ( BBIO 0.00%↑ ) / Sixth Street Partners / KKR HealthCare Royalty | 💊 ATTRUBY (acoramidis) + three pipeline launch assets | 🏷 Preferred Equity Financing

BridgeBio Pharma ($BBIO) raised $1 billion in preferred equity on July 1, 2026. Sixth Street Partners led the transaction with $800 million, and KKR HealthCare Royalty provided $133.9 million at close. The initial conversion price was set at approximately $138 per share, representing a premium of more than 100 percent to BridgeBio’s 30-day volume-weighted average price. The structure includes royalty features on revenue from ATTRUBY (acoramidis) and BridgeBio’s three additional pipeline drug launches expected over the coming years.

ATTRUBY targets transthyretin amyloid cardiomyopathy (ATTR-CM), competing primarily with Pfizer’s ($PFE) tafamidis (VYNDAMAX / VYNDAQEL), which generated approximately $4.3 billion in 2025 revenue. Alnylam’s ($ALNY) patisiran and vutrisiran represent RNA-based alternatives in the ATTR space with a distinct mechanism. BridgeBio has reported direct comparison analyses showing ATTRUBY’s superiority to tafamidis.

🧠 BPS Take: There is a lot of finance mumbo jumbo in the press release, so let me try and simplify this a bit. BridgeBio is getting $1B in funding that they’re going to use to ramp up the commercial scale of ATTRUBY and support the launches of three more of its products. The equity comes in the form of “convertible preferred equity”. Instead of selling a bunch of shares to raise the $1B and diluting its existing shareholders right away, Bridge is offering the new investors a 7% annual dividend plus the option to convert their entire preferred investment into common stock at a set price. If the investors want to, they can trade their preferred shares for common stock at $138 per share, double what Bridge’s stock has been trading at (and later at $153). So for them, they are collecting a cool $70M per year while still holding a $1B in equity in Bridge no matter which way the company stock price swings.

So in a sense, while this is structured as permanent equity, it acts similarly to a royalty partnership. BridgeBio gets the $1B scale-up capital fueled by the massive market potential of ATTRUBY and its upcoming pipeline. If those do well in the market, they are betting their stock probably doubles (if not more) within five years and those new shareholders decide to say goodbye to the dividend in favor of shares. By that time the pie has grown so big that the existing investors probably don’t care that they’re getting diluted, because their position is worth 2x or more what it was before.

The structure aligns the new investors to BridgeBio’s long-term success, while also protecting existing investors. The press release reads as a major vote of confidence in ATTRUBY’s commercial prospects in the ATTR-CM market vs. Pfizer’s , which is one of the fastest-growing cardiovascular rare disease markets in pharma, and Pfizer’s ($PFE) $4.3 billion VYNDAMAX franchise. We saw Apogee do a similar sort of deal with Blackrock before they got bought by AbbVie and we could see more of these sorts of structures that allow late-stage biotechs to raise non-dilutive funds to fund commercial launches, while still keeping acquisition options open.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

Pfizer sees another of its Seagen ADCs stumble, the first CAR-T for solid tumors wins approval, Trump might be on retatrutride, and the US-China deals drama reaches new heights.

All that and much more below!

Too soon? Tip me.

📡 PRESS RELEASE DECODER

What the press releases actually mean

Pfizer’s Seagen-acquired ADC misses Phase 3 OS in 2L+ non-squamous NSCLC, third Seagen ADC disappointment puts the $43B deal back on trial

📅 June 23 | 🏢 Pfizer ($PFE) | 💊 sigvotatug vedotin (B7-H4 ADC) | 🏷 Phase 3 Failure

Pfizer reported that sigvotatug vedotin failed to significantly improve overall survival versus docetaxel in pretreated nonsquamous non-small-cell lung cancer. It is the third Seagen originated ADC to disappoint following two prior misses, and the first asset from the 2023 Seagen acquisition to read out in a Phase 3 lung setting.

Pfizer paid roughly $43B for Seagen in 2023. The asset was positioned as one of the platform’s lead expansion plays into a post-IO chemotherapy benchmark. The company has not yet disclosed full subgroup data, biomarker stratification, or whether it will pursue a confirmatory analysis or label-friendly subset.

Biopharma Dive and Fierce Biotech both note this is the first new ADC from the Seagen acquisition to read out in Phase 3, with the prior two misses coming from legacy Seagen-stage programs.

🧠 BPS Take: The gut reaction here may be that this makes the $43B Seagen deal look even worse. I agree with that to some extent. None of Seagen assets have amounted to much on Pfizer’s topline, perhaps save for Padcev. Unless there is some home run asset living within the ADC pipeline that we don’t know about, the Seagen acquisition continues to look like an “all-in” bet that won’t pay off. We do need to caveat this NSCLC readout a bit though. This was in 2L+ NSCLC in patients without actionable genomic alterations. This has historically been an absolute graveyard for randomized studies. The TROP2 ADCs most recently failed to beat chemotherapy in this setting. Once patients fail PD-1 based regimens in 1L NSCLC, nothing has seemed to work. Most companies with novel assets in NSCLC don’t even look to develop in 2L anymore, opting to just go straight to 1L in combination with PD-1 instead. So given the high bar here, this asset may still have some potential in 1L NSCLC. We’ll just have to wait and see.

FDA Reopens AdComm Path for Previously-Rejected Replimune RP1 and Capricor Deramiocel, Reverses Regenxbio Navsunli CRL — The New CBER/CDER Are Revisiting Makary-Prasad-Era Decisions

📅 June 22 to June 26 | 🏢 FDA / Replimune ($REPL) / Capricor Therapeutics ($CAPR) / Regenxbio ($RGNX) | 💊 RP1 + nivolumab (melanoma), deramiocel (DMD cardiomyopathy), Navsunli / RGX-121 (Hunter syndrome / MPS II) | 🏷 Regulatory Reversals (Bundle)

Three regulatory decisions originally made under former Commissioner Marty Makary and former CBER Director Vinay Prasad got revisited in a single week. On June 26, the FDA accepted Replimune's third BLA resubmission for RP1 in combination with nivolumab for advanced melanoma as a complete class 1 response with an August 2, 2026 goal date, and notified the company to expect an Advisory Committee meeting in late July — the first AdComm in RP1's regulatory history after two prior rejections. On June 23, the FDA reversed its earlier position on Capricor's deramiocel BLA in DMD cardiomyopathy, scheduling an AdComm for July 29, 2026 after initially telling the company "an Advisory Committee meeting is not indicated at this time." And in late June, Regenxbio announced alignment with the FDA on the path forward for Navsunli (RGX-121), the AAV9 gene therapy for Hunter syndrome / MPS II, following the February 7, 2026 Complete Response Letter. A Type A meeting is expected in July with BLA resubmission planned for Q3 2026 using existing data.

🧠 BPS Take: This is not a broad regulatory tide lifting every cell and gene therapy program. It is the new CBER and CDER leadership working to rewind a backlog of decisions from the previous regime that were politically unpopular. Replimune’s RP1 AdComm is the FDA saying the rejection should have gone to public review the first time, not that oncolytic virus programs broadly have a clearer path. Capricor’s deramiocel AdComm is the same dynamic in DMD cardiomyopathy. Regenxbio’s CRL reversal is the FDA acknowledging the resubmission can proceed on existing data. Perhaps the string that ties all of this together is a reversion back to a more normal understanding of unmet need and a more liberal use of AdComs as a regulatory tool. All of this is occurring under the leadership of an interim commissioner. There is no guarantee that a new leader won’t exact their own personally-motivated agenda, but what has been clear from the Makary-Prasad era is that the FDA has received an outsized amount of mainstream media attention for the wrong reasons. Whoever the new permanent leader is would likely be someone who stays under the radar.

China NMPA Approves CARsgen’s Satri-cel as World’s First CAR-T for Solid Tumors — Claudin18.2+ Gastric/GEJ Cancer

📅 June 22, 2026 | 🏢 CARsgen Therapeutics ($CARS.HK / 2171.HK) | 💊 satricabtagene autoleucel (satri-cel, CT041) | 🏷 Regulatory Approval / Cell Therapy / Solid Tumors

China’s NMPA approved satri-cel, an autologous Claudin18.2-directed CAR-T, for adults with Claudin18.2-positive, HER2-negative advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma who have failed ≥2 prior lines. This is the first CAR-T globally to win approval in a solid tumor.

Pivotal data (CT041-ST-01, Phase 2): Median PFS 3.25 mo vs 1.77 mo for physician’s choice chemo; median OS 7.92 mo vs 5.49 mo. CARsgen pairs the cell product with a preconditioning regimen of low-dose nab-paclitaxel layered on top of standard lymphodepletion. Pricing is set at ~¥990,000 (~$146,000), and the product is on China’s new Commercial Health Insurance Innovative Drug List. Satri-cel also holds U.S. FDA RMAT designation in the same indication. Phase 1 work in pancreatic cancer is ongoing.

🧠 BPS Take: CAR-Ts have finally made it into solid tumors, which is a tremendous achievement for the class writ-large, even if this approval is restricted to China. Would this translate to the US/EU markets though? The magnitude of efficacy here is modest, with roughly 2-month improvement in PFS and OS. With the caveat that this was an entirely Chinese population, you have to ask yourself whether that level of benefit would drive commercial uptake in the US/EU if data were recapitulated here. The $150K price tag is amazingly cheap for an auto CAR-T and illustrates the COGS chasm between China and the West. There is almost no way that a US version would be priced that way. Still, this biomarker-defined slice (Claudin18.2+, HER2-) might be the right approach needed to make this sort of drug successful outside of China too. Perhaps not in end-stage gastric cancer, which is a relatively small population in the US to begin with before considering fitness for CAR-T, but moving it up into 2L+ setting vs. SoC. The target is clearly active, with zolbetuximab already approved in the 1L setting as well, so if Carsgen or other CAR-Ts advancing the same approach can find the right target patient population, perhaps there is a shot at an approvable and commercially viable product profile here in the west.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

STAT report sparks speculation that President Trump received compassionate use access to Lilly’s retatrutide; White House denies, but the political optics test for the GLP-1 category just arrived

📅 June 23 | 🏢 Eli Lilly ( ) / FDA / White House | 💊 retatrutide (LY3437943, GIP/GLP-1/glucagon triple agonist) | 🏷 Compassionate Use / Policy / Mainstream Crossover

On June 23, STAT News reported that Eli Lilly and the FDA granted compassionate use access to retatrutide, Lilly’s investigational triple agonist for obesity, to a 79-year-old male patient with refractory obesity, obstructive sleep apnea, and pulmonary hypertension. The request was submitted in April 2026 by Ranganath Muniyappa, a senior clinician at the National Institutes of Health. The patient reportedly had taken Zepbound (tirzepatide) for approximately one year without sufficient weight loss response.

The patient’s age (79 at time of application, now 80), the political connectivity implied by an NIH senior clinician routing the request, and the timing prompted widespread speculation that the recipient was President Trump, who turned 80 on June 14. The White House issued sharp denials through senior deputy press secretary Kush Desai and communications director Steven Cheung, both publicly attacking the STAT reporter on X. The White House and HHS did not respond to STAT’s pre-publication inquiries asking directly whether the president was the recipient.

Trump’s most recent physical reported his weight at 238 pounds, up 14 pounds from April 2025, approaching the BMI threshold for clinical obesity. He has previously told the New York Times he “probably” should take weight loss medication. Retatrutide remains investigational, with TRIUMPH-1 Phase 3 data showing 28.3% mean weight loss at 80 weeks. Lilly is preparing a regulatory submission with PDUFA timing not yet disclosed.

🧠 BPS Take: The mainstream framing is “is Trump on a secret weight loss drug and got special treatment.” The biotech-relevant insight is that the most potent obesity drug in clinical development may be stuck with potentially radioactive political baggage that Lilly has little ability to dump.

Compassionate use approvals for obesity drugs are extraordinarily rare. The FDA’s expanded access program was designed for life-threatening illness without alternatives, and obesity has historically not cleared that bar even for severe phenotypes. That an NIH senior clinician routed a compassionate use request for an investigational obesity drug, that Lilly accepted it, and that the FDA approved it tells you the regulatory framework around what counts as “life-threatening” obesity is being stretched in real time. Pulmonary hypertension and severe sleep apnea give the case its clinical justification, but the precedent matters.

How does this affect Lilly’s corporate reputation ahead of retatrutide’s filing? If the speculation continues to dominate health-adjacent news cycles, Lilly faces a problem they cannot solve through normal regulatory communications. This starts to fit more into the “crisis PR” bucket. But if not, it leaves Lilly in an awkward position, having to navigate some hairy questions about special treatment, Trump, and quid pro quo. Maybe the patient is the president, in which case Lilly will have to navigate the appearance of preferential access to an unapproved drug for the executive who controls the regulator approving it. Or maybe the patient is someone else with similar political proximity (a member of Congress, a senior official, a family member), in which case the same optics apply at a smaller scale. Or maybe the patient is an anonymous private citizen with no political connection, in which case Lilly cannot say so without violating patient privacy, leaving the speculation to compound.

As is the case with most things Trump-related, the news cycles shifts so quickly, so the general public may not even care about this story since there will be another crazy story about Trump the following week to take its place, so most likely Lilly is in the clear on this.

BINSA Adds Biotech to Outbound Investment Restrictions, Serapha/YolTech Launch Tests the Limits Days Later — The China Biotech Debate Has a Concrete Test Case

📅 June 2 / June 23 | 🏢 House Select Committee on China / RA Capital / RTW Investments / YolTech Therapeutics / Beam Therapeutics ( ) / Boundless Bio ( ) | 💊 Biotech Investment National Security Act (BINSA) | SERP-01 (base editing for AATD) | 🏷 Policy + Reverse Merger / Series A

On June 2, Reps. John Moolenaar (R-MI) and Debbie Dingell (D-MI) introduced the Biotech Investment National Security Act (BINSA), a bipartisan bill that would add biotechnology to the COINS Act's outbound investment scrutiny framework. The bill targets licensing, joint ventures, and equity investments that could transfer pharmaceutical IP or manufacturing know-how to China-directed entities, with Treasury required to issue rules within one year.

BINSA followed two megadeals that became the symbolic triggers: BMS's $15.2B alliance with Hengrui Pharma and Pfizer's $10.5B Innovent collaboration. Roughly 100 U.S.-China biotech licensing deals have been announced since the start of 2025, with cross-border transaction value reaching ~$136B in 2025 alone, up from less than $5B in 2020.

Three weeks later, the debate got its test case. On June 23, RA Capital and RTW Investments announced a $230M Series A and reverse merger to launch Serapha Bio, built around SERP-01, an in vivo base editing program licensed from China-based YolTech Therapeutics. SERP-01 targets the same SERPINA1 E342K mutation as Beam Therapeutics' BEAM-302, using a comparable lipid-nanoparticle approach. YolTech retains China rights, a minority equity stake, and over $2B in milestone eligibility. Boundless Bio is dissolving its ecDNA cancer program and ceding 96.3% of the combined entity to Serapha. Boundless shares jumped 87% on the announcement. Beam-focused investors framed Serapha as a Chinese copycat of BEAM-302 underwritten by U.S. VC capital. RA Capital's Peter Kolchinsky pushed back in "The paradox of biotech protectionism," arguing that walling off China biotech weakens U.S. competitiveness.

🧠 BPS Take: BINSA's odds of passage on its own are low given how few bills this Congress has enacted and the looming November elections. The realistic path is folding it into a year-end spending package or defense authorization bill, which is exactly how BIOSECURE moved. There is enough anti-China momentum in Congress for companies with active China deals to plan as though some version of BINSA becomes law in 2027.

Serapha exposes how hard the policy is to operationalize. SERP-01 was developed in China but will be developed and commercialized in the U.S. by a U.S. company employing U.S. scientists. It's not even the first deal of its kind. Atlas Venture and Bain used the same playbook to build Aiolos Bio around a Hengrui-licensed asset, sold it to GSK for $1B, then repeated it with Kailera Therapeutics, which delivered one of 2026's largest biotech IPOs. The "U.S. company or Chinese company" question doesn't have a clean answer, and that ambiguity is what Kolchinsky's defense leans on. The real nuance lives in the gradient: which deal structures trigger review, at what threshold, with what carve-outs. BINSA's current draft focuses on equity investments and joint ventures with licensing as a softer category, which would arguably permit Serapha's structure as-written.

There is no formal patent infringement allegation against YolTech or Serapha, just speculation from loud voices on Twitter. But the structural parallel — same target mutation, same delivery format, same class of editing — is the kind of fact pattern that could trigger a more formal legal offensive. YolTech's leadership also includes Zi Jun Emma Wang, who previously worked at Beam, a detail that was publicly visible on YolTech's site until recently.

Ultimately, China isn't going anywhere. In a decade it could be another country that emerges as the next arbitrage opportunity. Big Pharma will always partner with what they feel are the best drugs at the best values, and we can't look to VCs to distribute capital with a "patriotism-first" mentality. Their business is generating returns for their LPs, and they'll go wherever the value creation is ripest. We need right-sized regulation that levels the playing field, but that won't matter if the U.S. doesn't fix the underlying reason these deals are attractive: it is faster and cheaper to generate Phase 1 human data in China than in the U.S. HHS has proposed a streamlining package with clearer pre-IND data requirements, flexible trial protocols, and a rolling FDA submission platform. The question is whether those proposals translate into timeline and cost reductions that actually shrink the arbitrage.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Lilly Joins $100M Absci Public Offering Alongside Five Other Institutional Investors — ABS-201 Hair Loss Asset Gets Strategic Capital

📅 June 24 | 🏢 Eli Lilly ($LLY) / Absci ($ABSI) | 💊 ABS-201 (anti-PRLR monoclonal antibody for androgenetic alopecia and endometriosis) | 🏷 Strategic Equity Investment (Public Offering)

On June 24, Absci ($ABSI) priced a $100M underwritten public offering of 13.5M shares at $7.41 per share with participation from Eli Lilly ($LLY), Adage, BVF Partners, Columbia Threadneedle, Invus, Redmile, and an additional large investment management firm. The offering closed on June 25. The structure is an underwritten public offering of common stock, not a strategic partnership, and Lilly is participating as one of several institutional buyers rather than as a sole strategic investor with negotiated rights.

Proceeds will fund advancement of ABS-201, Absci’s AI-designed anti-PRLR antibody, across androgenetic alopecia (pattern hair loss) and endometriosis. ABS-201 reported positive interim Phase 1 data from the HEADLINE trial earlier in June, with the asset positioned as a novel mechanism (prolactin receptor antagonism) versus the incumbent androgen-pathway treatments (finasteride, dutasteride) and the topical vasodilator standard (minoxidil). Absci stock surged on the financing announcement.

🧠 BPS Take: This is not a strategic partnership and should not be read as one. I’ve seen a lot of articles and takes pop up talking about this as though Lilly is moving heavily into hair loss or that this is setting up for them to eventually acquire Absci. That is a pretty big stretch in my opinion. Lilly is one of seven institutional buyers in a public offering, participating at the same $7.41 per share as everyone else in the syndicate, getting straight equity and nothing else. This feels more like Lilly’s corp dev arm staying close to an interesting small-cap doing something outside Lilly’s existing therapeutic footprint.

But if we are going to speculate a little bit, let me throw one interesting scenario at you. Lilly has been building LillyDirect as a cash-pay direct-to-consumer channel for Foundayo and Zepbound, and the telehealth players who serve as the actual front door for those drugs — Hims, Hers, Ro — also sell hair loss and sexual wellness treatments as their core verticals alongside GLP-1s. What if Lilly decides to integrate that front door one day? As Lilly’s portfolio of cash-pay-appropriate medicines expands beyond GLP-1s — hair loss with ABS-201 or similar in 2028-2030, sexual dysfunction, and other lifestyle-adjacent indications as employer plans push them out of insurance coverage — the strategic value of owning the full channel your self compounds. At some point, the math may tip and building or acquiring the front door becomes the obviously correct move rather than a speculative bet.

The other piece of the calculus that gets underweighted in telehealth coverage is the leverage asymmetry. Hims, Hers, and Ro built their growth primarily on compounded GLP-1s during the shortage window. As FDA enforcement on 503A and 503B compounding tightens, that revenue stream is structurally vulnerable. The telehealth players have shifted toward distributing branded Zepbound and Foundayo at no real margin, only to sell wraparound services and membership fees that actually drive their profitability. The asymmetry is in Lilly’s favor. If Lilly decided to restrict distribution arrangements with any specific telehealth player, that player’s business gets restructured overnight. The telehealth players have no equivalent leverage because they do not manufacture the drugs, they do not own the IP, and they cannot substitute. The GLP-1 market is functionally a two-player oligopoly between Lilly and Novo right now, with Lilly leading on growth and the next wave of efficacy via retatrutide. Once the compounding question is fully resolved by the FDA, Lilly’s structural leverage over the telehealth channel is essentially complete.

The Absci $100M is not evidence that this strategy is being executed. It is the kind of capital deployment that keeps the option open as the portfolio expands. ABS-201 is Phase 1 and may or may not be the asset that anchors a future Lilly cash-pay franchise. But the broader pattern — LillyDirect expansion, Foundayo’s cash-pay-first launch in April, equity participation in differentiated cash-pay assets — is consistent with a dominant company that has the strategic flexibility to own the front door (rather than rent it) if they want to.

Novartis pays $105M upfront for Antares’ “undruggable” cancer small molecules, discovery-stage deal with a $1.9B biobuck tail

📅 June 24 | 🏢 Novartis ( ), Antares Therapeutics | 💊 Undisclosed small-molecule programs against traditionally “undruggable” oncology targets | 🏷 Licensing / Discovery Deal

Novartis and Antares Therapeutics entered a multi-target research collaboration with $105M upfront and up to $1.8B in milestones plus royalties, roughly $1.9B in headline biobucks per Reuters coverage.

Endpoints reports the lead programs are positioned as first-in-class, and Antares retains rights on some indications.

Fierce Biotech notes the deal sits at the upper end of recent discovery-stage upfront benchmarks.

🧠 BPS Take: As a reminder, Antares is a spinout of Scorpion Therapeutics, which carried over the leftover assets into Antares, after Lilly bought one of the Scorpion assets last year. $105M upfront and up to $1.9B in total value closely mirrors the Regeneron Parabilis numbers from a couple months ago ($125M upfront, up to $2.3B), however the Regeneron upfront contained a $75M equity investment with Parabilis IPO’ing shortly thereafter. Neither company has disclosed what targets they are going after, other than to say they are “historically undruggable”. There are a few major culprits that sit within that group: several targets within the RAS family, MYC, TP53, and WNT/Beta-catenin. I’m curious to see if any targets from these groups make the list and how they differ from Antares’ wholly owned programs that would conceivably make up the bulk of their company valuation.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

Abbvie looks to buy Apogee. Neumora watched navacaprant flame out in both KOASTAL-2 and KOASTAL-3, sending the stock to 98 cents after a 45% drop and a 35% workforce reduction, a rough end for a program that carried real expectations. We also cover Jazz’s $56M upfront deal with AbCellera in a T-cell engager collaboration worth up to $4.1B. Plus, major reversals of the Prasad-Makary era FDA rulings, with new green lights coming for UniQure’s Huntington’s Disease gene therapy and Moderna’s flu vaccines.

All that and more below. Let’s get into it!

⏪ Prior-Week Update(s)

Kardigan completed its upsized $400M IPO (25M shares at $16, top of range) with shares closing day-one at $22.00 (+37.5%), confirming the cardio-IPO premium thesis published in last week’s IPO Bundle. You can check out the full write-up on Kardigan in last week’s edition of LWTB.

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📡 PRESS RELEASE DECODER

What the press releases actually mean.

Navacaprant fails primary endpoint in both KOASTAL-2 and KOASTAL-3 Phase 3 MDD trials. Neumora discontinues program, lays off 35%, pivots to Alzheimer’s and obesity

📅 June 15 | 🏢 Neumora Therapeutics ( ) | 💊 navacaprant (NMRA-335140), KOR antagonist for MDD | 🏷 Phase 3 Failure + 35% Layoffs

Neumora Therapeutics announced on June 15 that navacaprant, its kappa-opioid receptor antagonist for major depressive disorder, failed to meet the primary endpoint in both KOASTAL-2 and KOASTAL-3, the company’s two confirmatory Phase 3 trials. Key secondary endpoints also missed in both studies, leaving the program with no positive signal across either trial.

The failures complete a 0-for-3 record in Phase 3 for navacaprant, following the earlier miss in KOASTAL-1. Shares fell approximately 45% to 98 cents in pre-market trading on the news, putting the stock below one dollar.

Neumora is discontinuing the navacaprant program entirely and announced a 35% reduction in workforce. The company stated it will redirect resources toward Alzheimer’s disease and obesity.

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🧠 BPS Take: Three Phase 3 swings and three misses in Major Depressive Disorder (MDD). That right there is psychiatry drug development in a nutshell. The KOR-antagonist mechanism in MDD appears to be finished as a clinical thesis. Neumora ran a clean, adequately powered program, which makes the 0-for-3 outcome pretty definitive. It means the biology probably doesn’t work the way the field hoped, not that the placebo effect or trial design muddled the results. Any other players pursing the same mechanism of action in MDD are on notice.

The psychiatry novel-mechanism graveyard keeps collecting names: burned years and capital on zuranolone in MDD before finding a narrower regulatory path, and absorbed a Phase 3 failure on its adjunctive schizophrenia program for COBENFY (xanomeline/trospium). It feels like psychiatry drug development is harder than ever, but that is how it has always been.

Psychedelics and their variants continue to be the most attractive opportunity to me in this space, and with increased deal flow into that area over the last several months from the likes of Lundbeck, Otsuka, and AbbVie, among others, I think its clear larger players are getting smart to that too.

UniQure stock surges 80% after FDA reverses position on Huntington’s gene therapy filing; AMT-130 BLA submission planned for Q3 2026

📅 June 17 | 🏢 uniQure ( ) | 💊 AMT-130 (AAV5-miHTT gene therapy for Huntington’s disease) | 🏷 Regulatory U-Turn / BLA Path Cleared

UniQure announced on June 17 that the FDA has reversed its prior position on the regulatory path for AMT-130, the company’s AAV-delivered gene therapy for Huntington’s disease, and will now accept the three-year analysis from the ongoing Phase 1/2 study as the primary basis for an accelerated approval filing. The company plans to submit its BLA in Q3 2026. Shares surged approximately 80% to $48.51 in premarket trading on the news.

The reversal is a sharp departure from the FDA’s position in March 2026, when the agency told UniQure the three-year dataset would not be sufficient and that additional trial data would be required. That March decision sent the stock down roughly 40% at the time and forced UniQure back to the negotiating table.

The shift in agency posture occurred after the departures of former FDA leadership Marty Makary and Vinay Prasad, both of whom held top positions when the original guidance was issued. UniQure and the FDA are now working toward alignment on the confirmatory study design, with the company proposing concurrent standard-of-care control rather than the sham procedure originally requested by the agency.

🧠 BPS Take: Well, well, well. How the turntables turn. It seems like this new interim FDA regime is keen to undo many of the unpopular decisions made in the Prasad-Makary era. Both this UniQure news and the later Moderna news (below) we cover are signals of that.

If you’re a melanoma patient or a Replimune shareholder, that has to feel like great news for you too, because it aligns well with the UniQure story. Huntington’s is a brutal disease with limited options and patients with incredibly high unmet need. The same can be said for melanoma patients who fail PD-1s, but I am sure Replimune will be holding its breath until their final decision comes down.

The new leadership at the FDA has a new evidence vs. unmet need calculus, that feels a bit more traditional and grounded in reality. What’s hard to tell at this juncture is if this is indeed a reversion back to normal with how the FDA views single-arm study data in high unmet need indications, or simply the FDA trying to undo specific wrongs that got them a lot of bad press, with more unpredictability ahead for the industry.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma.

Moderna’s mRNA flu vaccine clears VRBPAC 9-0 in twin votes; February refusal-to-file gets fully reversed and Prasad-era FDA gets a quiet rebuke

📅 June 18 | 🏢 Moderna ($MRNA) / FDA / HHS / ACIP | 💊 mFLUSIVA (mRNA-1010), seasonal influenza vaccine | 🏷 FDA AdComm + Vaccine Policy

The FDA’s Vaccines and Related Biological Products Advisory Committee voted 9-0 on June 18 in two back-to-back votes: full approval recommendation for mFLUSIVA in adults 50 through 64, and accelerated approval recommendation for adults 65 and older. This was VRBPAC’s first new vaccine review in over three years and the first vaccine to clear an FDA advisory committee under the second Trump administration. The PDUFA date is August 5, 2026. The FDA has historically followed AdComm recommendations 84% of the time from 2020 through 2025 per a Jefferies analysis.

In February 2026, the FDA’s Center for Biologics Evaluation and Research under then-director Dr. Vinay Prasad issued a refusal-to-file letter, declining to even review Moderna’s application on the grounds that the control group did not reflect best-available standard of care. Days later, under public criticism, the agency reversed itself and accepted the filing. Prasad left the FDA at the end of April amid reports of interference with drug reviews and a workplace conduct investigation. Former Commissioner Marty Makary, who had defended Prasad through multiple controversies, departed shortly after.

The Phase 3 trial in approximately 40,000 adults showed a roughly 27% relative reduction in confirmed influenza cases versus a standard-dose comparator. FDA reviewers in the briefing documents noted limited data in immunocompromised and frail adults but concluded the package “met all prespecified sequential success criteria.” Moderna shares were up 28% since briefing documents released earlier this week. mFLUSIVA carries an estimated $1 billion revenue opportunity for $MRNA, which lost $2.8 billion in 2025 and has a 2028 breakeven goal that the February RTF had materially threatened.

🧠 BPS Take: Both Prasad and Makary are gone, and the same agency that refused to file in February held a 9-0 twin vote in June on essentially the same dataset. That tells you the February RTF was a unilateral one and the broader CBER staff was always in a different place than its leadership. More “normal” less personal FDA rulings seem like they are ahead, especially given the VRBPAC was unanimous. That should be a welcome sign for vaccine developers more broadly.

The ACIP side remains the problem. Secretary Kennedy gutted the CDC’s vaccine recommendation committee earlier this year, the replacement has no published cadence, and without an ACIP recommendation before fall 2026, Moderna’s commercial launch slips into 2027 regardless of whether the August 5 PDUFA lands on time. mFLUSIVA’s $1 billion opportunity is a much needed boon to Moderna, which has seen downward stock pressure post-COVID. An ACIP recommendation would go a long way towards reinvigorating Moderna’s topline and place less pressure on its cancer vaccines to drive an era of future growth.

FDA’s Commissioner’s National Priority Voucher (CNPV) pilot program draws industry concern over criteria opacity and potential to be used for broader policy agenda

📅 June 19 | 🏢 POLICY | 💊, | 🏷 Policy/FDA

The FDA’s Commissioner’s National Priority Voucher (CNPV) pilot program is drawing industry scrutiny over how recipients are selected and whether the program serves purposes beyond pure review efficiency. The CNPV compresses standard 10-to-12-month review periods by roughly four months, placing it in the same general territory as the existing Priority Review Voucher (PRV) system while running entirely on Commissioner discretion rather than statutory criteria.

Achieve Life Sciences ($ACHV) received a CNPV for cytisinicline, a smoking cessation candidate with a PDUFA date of June 20. The ACHV grant is among the clearest public examples of how the program operates in practice, though FDA has not published formal selection criteria that would allow sponsors to assess eligibility in advance.

Industry trade groups have flagged the criteria opacity as a structural problem nine months into the pilot. Without codified standards, sponsors cannot predict CNPV access, which complicates development timelines, partnership valuations, and out-licensing deal terms that depend on regulatory timing assumptions.

🧠 BPS Take: I think pretty much every biotech company is in favor of a faster review process. But having some codified guidelines on what is and isn’t eligible is important. Right now, the CNPV feels more like a political tool for playing favorites. For sponsors in therapeutically and politically aligned areas, rare pediatric disease, antimicrobials, US-manufactured products, a CNPV is a major accelerator to market. Sponsors in less-aligned areas cannot model it at all because selection criteria remain unpublished a full year into the pilot.

I also somewhat question whether we need a CNPV at all, or if there are other mechanisms the FDA already has within its disposal to accelerate drug approvals. Perhaps wider use of emergency use authorization (EUA) could function similarly. Many were calling for EUA for daraxonrasib after seeing the ASCO 2026 data. Perhaps a combo of rolling submission plus EUA can work a bit more elegantly than the more opaque CNPV system as it currently stands. For the CNPV to work there should be clear rules so that it can’t be perceived as arbitrary, or the Commissioner picking their favorites, or worse, influenced by politicians and their special interests.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal.

🚨WEEKEND RUMOR🚨
AbbVie nears $10.9B all-cash acquisition of Apogee Therapeutics at 60% premium for next-gen IL-13 atopic dermatitis franchise

📅 June 19 (rumored) | 🏢 AbbVie Apogee Therapeutics ( ) | 💊 zumilokibart (APG777) IL-13 mAb + APG808 IL-4Rα mAb + APG279 IL-13/OX40L bispecific | 🏷 M&A Acquisition (Rumored, FT/Reuters)

UPDATE: As of Monday (6/22) this deal became official. You can see AbbVie’s PR here and there post-deal presentation. No changes to the analyses below.

According to a June 19 Financial Times report citing people familiar with the matter, AbbVie is closing in on an all-cash deal to acquire Apogee Therapeutics for approximately $10.9 billion. The reported price represents a roughly 60% premium to Apogee’s June 18 closing price of $90.38 and values the company at roughly 60% above its market cap of $6.81 billion at the time of reporting. An announcement could come as early as Monday, June 22, contingent on negotiations closing without last-minute friction. Both AbbVie and Apogee declined comment when reached by Reuters.

Apogee’s lead asset is zumilokibart (APG777), an IL-13 monoclonal antibody being developed in atopic dermatitis as a Dupixent (dupilumab) and Ebglyss (lebrikizumab) competitor with a differentiated half-life engineered for quarterly or biannual subcutaneous dosing. Positive Phase 2 Part B 16-week data have been reported, with Phase 3 enrollment underway. The pipeline also includes APG808, an IL-4Rα antibody in Phase 1b for asthma with a 50% FeNO reduction signal at 12 weeks, and APG279, an IL-13/OX40L bispecific in earlier development. Apogee secured a $1.3B financing package from Blackstone Life Sciences in May 2026 to support APG777 late-stage development and potential commercialization.

🧠 BPS Take: There’s no need to really sell anyone on the strategic fit of this deal. AbbVie is the premier autoimmune disease company, even after HUMIRA has gone generic. SKYRIZI and RINVOQ have turned into cash cows. SKYRIZI dominates in psoriasis and IBD, and RINVOQ covers a broad footprint, but AbbVie lacks a premier, ultra-long-acting biologic specifically tailored to corner the atopic dermatitis and asthma markets, where Regeneron’s DUPIXENT has been the market leader.

AbbVie has been running head-to-head RINVOQ trials against DUPIXENT for a while trying to dislodge it in atopic dermatitis, with mixed commercial traction despite winning data. RINVOQ is limited by a black box warning, relegating it to a second-line setting. APG777’s quarterly-to-biannual dosing is the differentiation that could finally crack the dosing-burden argument that has kept Dupixent’s bi-weekly injection competitive.

Apogee took a $1.3B Blackstone royalty financing in May to fund Phase 3 commercialization on its own. Six weeks later they’re selling to AbbVie at a 60% premium. That sequencing tells me Apogee management was ready to go it alone until AbbVie came knocking. It will be interesting to see what AbbVie does about the Blackstone deal. Blackstone was set to give Apogee $800 million of synthetic royalty and up to $500 million of debt. The $800M is in exchange for low-to-mid single digit tiered royalties for a term of 15 years on worldwide annual sales of zumilokibart. The royalties do decrease based on sales with no royalties on global annual sales in excess of $8B, but I can’t imagine AbbVie wants to kick points on this product to Blackstone, so I would guess they will look to subsequently buy themselves out of this deal whenever the acquisition closes.

Jazz pays AbCellera $56M upfront in up-to-$4.1B T-cell engager partnership for GI cancers. Up to $792M milestones per program plus tiered royalties

📅 June 17 | 🏢 Jazz Pharmaceuticals ( ) / AbCellera ( ) | 💊 Next-gen T-cell engaging multispecific antibodies (GI cancers/solid tumors) | 🏷 Licensing / Collaboration Deal

Jazz Pharmaceuticals and AbCellera announced a collaboration on June 17 to discover next-generation T-cell engaging multispecific antibodies targeting GI cancers and solid tumors. Jazz is paying $56 million upfront for rights to two discovery programs, with an option to add a third program within 12 months for up to $28 million more.

Each program carries up to $792 million in option fees and development, regulatory, and commercial milestones, with tiered royalties on net sales also included. The total potential deal value across all programs reaches $4.1 billion, though that figure assumes full option exercise, program advancement, and milestone achievement across multiple indications.

AbCellera will apply its antibody discovery platform to generate multispecific candidates. Jazz retains commercial rights and will lead development. The collaboration covers solid tumor indications with an emphasis on gastrointestinal cancers, a space where T-cell engaging formats have seen intensifying industry investment through 2025 and into 2026. No specific molecular targets for the programs were disclosed at announcement.

🧠 BPS Take: This feels like a well-balanced deal for Jazz. $56M is not much to pay upfront, and the backloaded economics are on a per program basis, given Jazz a lot of optionality. You would think for a partnership with an AI for drug development player like AbCellera, the upfront would be pricier, but these are still very early (discovery) stage programs that carry a lot of uncertainty. Perhaps this sort of deal can serve as a template for how mid-cap pharma builds pipeline in 2026 without committing acquisition-scale capital. Rather than paying premiums in the billions, Jazz is renting shots on goal. There are a plethora of AI platform discovery plays out there and it may be wise for the mid-caps to poke and around and see if they can find some low-risk high-reward type opportunities like this if they are eager to get into the AI space.

Denali sells priority review voucher for $195M, signaling rebound in PRV market after Congressional reauthorization

📅 June 18 | 🏢 Denali Therapeutics ( ) | 💊 PRV from Avlayah approval (Hunter syndrome) | 🏷 PRV Sale / Non-Dilutive Financing

Denali Therapeutics announced on June 18 that it has sold the priority review voucher earned from the March 2026 FDA approval of AVLAYAH for Hunter syndrome for $195 million. The buyer was not disclosed. Denali stated proceeds will support its TransportVehicle blood-brain barrier delivery platform and downstream pipeline including DNL126 (Sanfilippo syndrome type A), DNL593 (GRN-related FTD), DNL952 (Pompe disease), and DNL628 (Alzheimer’s disease).

The $195 million sale represents a meaningful price rebound for PRVs after a period of compression. Recent comparable transactions include Zevra Therapeutics selling a PRV for $150 million in 2024 following the Miplyffa approval, and Jazz Pharmaceuticals selling one for $200 million in January 2026 while the rare pediatric disease PRV program was awaiting Congressional reauthorization. The program lapsed in December 2024 and was reauthorized in February 2026 as part of a spending bill that also included PBM reform provisions.

PRVs are granted upon approval of drugs designated as rare pediatric disease therapies and can be redeemed by the holder for a four-month accelerated review on a different drug or sold to a third party for non-dilutive capital. Historical PRV pricing peaked at $350 million in the early years of the program and has fluctuated since.

🧠 BPS Take: This transaction lands inside the same week that the FDA’s Commissioner’s National Priority Voucher (CNPV) pilot is drawing industry criticism for opacity and discretionary selection. The two voucher programs are not substitutes for one another. The PRV market has an easy to determine fair market value. At one point PRVs were worth as much as $300M and then settled in at $100M, only to climb up to roughly $200M in recent years. For companies, this is predictable enough to underwrite in development planning, and produces non-dilutive capital that companies like Denali can deploy against pipeline expansion. T

For Denali specifically, the timing is sharp capital management. AVLAYAH is in its launch year, the TransportVehicle platform has a deep pipeline that needs funding, and pulling $195 million in non-dilutive capital to fund other high risk neurology programs can be a major stabilizing force.

I’m curious to see who the buyer of this PRV turns out to be. We typically won’t be able to figure that out until a filing or approval comes through where that voucher was redeemed, but there aren’t that many companies that have $200M lying around to spend on PRVs.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

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Traditional autologous ex vivo cell therapy has largely fallen out of favor. Attention (and dollars) are far more focused on in vivo approaches that massively condense the cost, speed, and complexity associated with the cell therapy supply chain.

The early data from this field has been really promising. At ASCO, Kelonia (newly acquired by Lilly ) continued to show a 100% overall response rate (ORR) in multiple myeloma, with more patients and longer follow-up. Just recently, at EHA, Legend Biotech also showed a 100% ORR with 83% complete response (CR) rate in patients with Non-Hodgkin’s lymphomas. And not too long before that, CREATE Biomedicines raised $122M in funding to take more of their programs into the clinic.

Most of the big newsy readouts coming out of ASCO this year were also from outside traditional cell therapy, with it feeling like targeted therapy approaches (whether they be small molecule, ADCs, or otherwise), were stealing the show, and that is justified.

But amidst all the focus on other areas, ASCO did bear some meaningful, albeit iterative, progress against solid tumors. Here are three updates that caught my attention and speak to the iterative progress cell therapy is making in treating solid tumors.

1️⃣ Obsidian’s OBX-115 Posts 67% ORR in Post-Checkpoint Melanoma With No IL-2, Outpatient Lymphodepletion, and an Optional Needle Biopsy

Asco 2026 Agni Rp2d N15 Final

1.08MB ∙ PDF file

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Obsidian presented updated RP2D data for OBX-115 in advanced melanoma that progressed on or after checkpoint inhibitor therapy.

In 15 patients treated at DL3/RP2D (100 × 10⁹ cell maximum), OBX-115 delivered a 67% ORR (13% CR) (10/15; 2 CRs, 8 PRs), a 93% DCR, and tumor burden reduction in 83% of patients. Median DOR was not reached (range 1.1+ to 14.9+ months) at a median follow-up of 4.3 months. Responses were observed across the hardest disease subsets: 73% had prior anti–PD-1 plus anti–CTLA-4 combination exposure, 53% were ICI primary-resistant, and the cohort included BRAF-mutant, mucosal, and acral subtypes.

Safety differentiation showed up too: exclusively low-dose lymphodepletion (Cy 750 mg/m² × 3, Flu 30 mg/m² × 4), no IL-2 in the regimen, CRS in 33% with one Grade 3 event, no DLTs, no ICANS, no ICU transfers, no treatment-related mortality, and 100% of acetazolamide re-dosing handled in the outpatient setting.

Tumor tissue procurement was feasible via core needle biopsy in 2 of 15 patients (both responded). ctDNA dropped by Day 14 in all responders, with 3 clearing entirely.

What I appreciate about OBX-115 is that it is an asset that is intentionally designed to address many of the major bottlenecks that have held first-generation TIL therapies, namely Iovance’s AMTAGVI (lifileucel), back from major market adoption. AMTAGVI’s launch has been constrained by the regimen itself: high-dose IL-2 mandates ICU-level monitoring, myeloablative lymphodepletion locks patients into inpatient stays, surgical tumor harvest limits the patient pool to fit patients with accessible lesions, and the time to treatment is still approximately two months long.

OBX-115 offers a solution to most of those barriers. Swapping out IL-2 for its own acetozolamide triggered membrane-bound IL-15 based cytokine support means patients can avoid additional in-patient days post-infusion. It also offers docs the ability to re-trigger IL15 stimulation and help drive more durability response days after cells have been infused. Low-dose lymphodepletion means outpatient-compatible administration. The core needle biopsy offering also adds flexibility to the manufacturing process, offering a less invasive path of cell collection and thus more patient eligibility. However, given this was only feasible in two of fifteen patients in the study, I am less optimistic that this will be a commonly used feature in the real-world setting. Core needle biopsy also gets more challenging as you move into non-skin cancers.

However, if you are an oncologist who has been reluctant to refer patients for AMTAGVI because the regimen is brutal and the logistics are punishing, OBX-115 is the version of TIL therapy you would be more likely to use. AMTAGVI is a good drug for the sub-segment of people who can receive it, and in the thirty-ish percent of patients who end up getting a response, that response tends to be quite durable. So the problem you need to solve is upstream of the treatment. How do you remove barriers to get more people onto therapy? Or how do you more quickly select the patients who will do well on the therapy?

A 67% ORR in 15 patients at 4.3 months of follow-up is not the same readout as AMTAGVI’s 31.4% ORR in the C-144-01 registrational dataset with 36.5-month median DOR, or the 44% real-world ORR Iovance has reported. But it is an early signal that adds more proof to the differentiation case of OBX-115. The engineering that went into its cell design seems to be driving up efficacy. That is likely due to both the higher percentage of CD8 T-cells in the OBX-115 (98%) and the built-in IL-15 stimulation. More longitudinal data is needed, but this is a promising sign that OBX-115 has raised the bar for TIL efficacy in a post-PD-1 setting.

The trade-offs and remaining challenges of this approach are clear as well though. Adding IL-15 to the mix adds cytokine release syndrome (CRS) back on the table as an on-target AE. TILs on their own don’t generate CRS or neurotoxicity/ICANS, since they’re just natural unmodified T-cells. Obsidian has also done nothing in this iteration to solve the major manufacturing challenges associated with TILs. This is conceivably still a product that takes 1-month plus to manufacture, especially if you’re dosing this at 83B cells. You can’t really speed up cell division more than it already is in an ex vivo centralized manufacturing process, where T-cells are getting every flavor of biological accelerator in the bioreactor.

Still, this is at least a few steps in the right direction, and should serve as a welcome addition to the melanoma armamentarium if/when this is approved. Nothing really works in melanoma after you fail PD-1 based therapy other than AMTAGVI, but not enough people are eligible to receive it. Obsidian’s next readout is expected to be in lung cancer in 1H 2027.

2️⃣ Immatics’ IMA203CD8 Posts 63% ORR in Heavily Pretreated Gynecologic Cancers at ASCO 2026

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

GSK dropped its biggest deal ever, paying $10.6 billion for Nuvalent. Tango therapeutics wows with new PDAC combo data. Lots of GLP-1 data presented at the ADA 2026 conference, but Lilly’s retatrutide sill reigns supereme. Parabilis shattered the biotech IPO record at $670 million, and Takeda’s zasocitinib crushed SOTYKTU in a direct head-to-head.

All that and more below. Let’s get into it!

📡 PRESS RELEASE DECODER

What the press releases actually mean

Tango’s Vopimetostat plus Daraxonrasib Hits 92% ORR in Heavily Pre-Treated MTAP-Deleted Pancreatic Cancer

📅 June 8, 2026 | 🏥 Tango Therapeutics (), Revolution Medicines ( ) | 💊 Vopimetostat (MTA-cooperative PRMT5 inhibitor) plus daraxonrasib or zoldonrasib (RAS(ON) inhibitors)

Tango reported initial Phase 1/2 combination data for vopimetostat plus Revolution Medicines’ RAS(ON) inhibitors in MTAP-deleted RAS-mutant cancers. In the vopimetostat plus daraxonrasib arm, 12 evaluable second and third line PDAC patients delivered a 92 percent ORR (11 of 12, nine confirmed), 100 percent DCR, and a 90 percent six-month PFS rate with median PFS not reached. Three NSCLC patients in the same combination delivered 100 percent ORR. The vopimetostat plus zoldonrasib arm in 27 evaluable PDAC patients delivered 52 percent ORR, 96 percent DCR, and 74 percent six-month PFS. Both combinations were well tolerated with no Grade 4 or 5 related AEs and no AE-driven discontinuations. The population was heavily pre-treated with more than half in third line and 70 to 77 percent with liver metastases. Tango plans to advance vopimetostat plus daraxonrasib into Phase 3 in first-line MTAP-deleted PDAC.

🧠 BPS Take: Coming off of the stellar daraxonrasib data we saw at ASCO in 2L+ PDAC, this combo data from Tango continues to imbue promise for the future treatment paradigm in PDAC and reinvigorate interest in the synthetic lethality mechanisms. MTAP-deleted PDAC represents roughly 40% of the market. In these types of tumor, PRMT5 inhibition works by completely shutting down an already weakened, vital cellular regulator that is already being throttled by a buildup of metabolic waste (MTA), pushing the cancer cell over the edge into cell death while leaving healthy cells unharmed. Adding KRAS inhibition onto that cuts off the tumors primary growth engine, leading to the synergistic uptick in ORR.

This is a small samples size (n=12) and short follow-up, but its rare to get this high of an ORR and have it not mean anything, especially when you consider SoC in these patients was generating single-digit ORRs. Credit to the Tango team too for planning ahead and doing a combo study with daraxonrasib, even before it became standard of care in PDAC. That shows quality product planning, anticipating the changing SoC.

You can imagine Tango is now on the BD radar for many companies with these data. BMS has their own PRMT5 inh in P2/3 and there are a slew of at least a couple dozen other PRMT5 inhibitor in active clinical development across the US, EU, and China. Notably Amgen and GSK previously discontinued their own PRMT5 programs. One name to track in this space is Ideaya ( ), which is developing IDE892 (PRMT5 inh) and is also targeting PDAC in combination with Roche’s pan-RAS inhibitor (RG6505).

Takeda’s $4B TYK2 Bet Pays Off: Zasocitinib Clears Skin at 2.5x the Rate of SOTYKTU in Head-to-Head Phase 3

📅 June 11 | 🏢 Takeda ( ) | 💊 zasocitinib | 🏷 Phase 3 Head-to-Head Data

Takeda ( ) announced Phase 3 results showing zasocitinib achieved 35% PASI 100 (complete skin clearance) compared to approximately 14% for SOTYKTU (deucravacitinib, Bristol Myers Squibb, $BMY) in a direct head-to-head trial in patients with moderate-to-severe plaque psoriasis. The 2.5x superiority on complete skin clearance was statistically significant. This follows a prior head-to-head study in which zasocitinib also outperformed Amgen’s ($AMGN) OTEZLA (apremilast).

Takeda acquired zasocitinib from Nimbus Therapeutics for $4 billion upfront in 2022, at a time when zasocitinib had no approved indication and the deal was widely viewed as expensive for an early-stage asset. SOTYKTU, the first-approved TYK2 inhibitor, generated $291 million in 2025 revenue. BMS has separately signaled it plans to reduce promotional investment in SOTYKTU in dermatology in a number of markets. The next major readout for zasocitinib is in inflammatory bowel disease, covering ulcerative colitis and Crohn’s disease, expected later in 2026.

🧠 BPS Take: Takeda paid $4 billion upfront for zasocitinib, an “AI-designed” drug, when the asset had no approval and the TYK2 proof of concept was still being established. Many called that an expensive bet back in 2022. A 2.5x head-to-head win on complete skin clearance over an approved in-class competitor makes it look like an underpay in retrospect.

The next major readouts are in IBD, with P2b data in Crohn’s and Ulcerative Colitis, two massive markets, upcoming by the end of this year. AbbVie’s RINVOQ (upadacitinib) and J&J’s biologic agents dominate that space, with RINVOQ alone doing over $5 billion annually across indications. If TYK2 inhibition works in IBD with clinical superiority data, this franchise becomes a genuine multi-billion dollar bet. SOTYKTU itself failed in IBD and a win there would further validated the precision-targeting of TYK2 via an AI-optimized drug design. The IBD data is the moment this story either gets much bigger or stays a dermatology niche win.

Furthermore, this could be the first actual win for AI-designed drugs, which to this point have largely been unimpressive in clinical studies. SOTYKTU came first, but Nimbus and Schrodinger used their advanced computing tools to look at SOTYKTU and figure out how to optimize it — that to me is where AI for drug development is really able to showcase its value today. Once you know the target and have some prior attempts at hitting that target, use that data to figure out how we can really hit that target much more cleanly.

ADA 2026 Bundle: Pfizer, Roche, and Novo Show They Are All Competing for the Same Patients Against Lilly

📅 June 8-11 | 🏢 CMS/HHS + Eli Lilly ( ) + Pfizer ( ) + Roche ( $RHHBY ) + Zealand Pharma ( $ZEAL ) + Novo Nordisk ( ) | 💊 WEGOVY / ZEPBOUND / FOUNDAYO / retatrutide / berobenatide / enicepatide / CagriSema |

At ADA 2026, Lilly presented extended Phase 3 data from TRIUMPH-1 for retatrutide: 28.3% mean weight loss at 80 weeks (70.3 lbs), with 45.3% of patients achieving 30% or greater weight loss and 65.3% reaching a BMI below 30. Pfizer’s berobenatide showed approximately 16% weight loss by 60 weeks in the Phase 2b VESPER trial. Roche-Zealand’s enicepatide (CT-388), a dual GLP-1/amylin agonist, showed 18-22.5% placebo-adjusted weight loss at the highest dose tested. Novo Nordisk’s CagriSema showed approximately 14.2% weight loss in the REIMAGINE T2D trial in patients with type 2 diabetes.

🧠 BPS Take: Pfizer at 16% and Roche-Zealand at 18-22% are real numbers, but they are not threatening Lilly’s ceiling. Retatrutide at 28% with nearly half of patients losing 30% or more is a different category of efficacy. Novo’s CagriSema at 14% in a T2D population is trailing across all mechanisms. The market will expand fast enough that multiple players can build profitable franchises here, but it will be important for each to find its niche population as treatment moves towards a more precision-medicine type approach. Future pricing considerations will also be a major driver here, as many employer plans are looking drop coverage of GLP-1 drugs in 2027 because they are getting too expensive, making the more price-transparent cash-pay direct-to-consumer market even more critical for driving commercial success.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

Not much I wanted to highlight in this section this week, so I’ll take this time to plug my paid tier 😅.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

IPO Bundle: Parabilis Sets a New Biotech IPO Record at $670M While Kardigan Lines Up Cardiovascular. The Window Is Fully Open

📅 June 10 to 11, 2026 | 🏥 Parabilis Medicines ( ), Kardigan ( $KARD ), Regeneron ( ) | 💊 Zolucatetide (Helicon peptide targeting beta-catenin), Kardigan cardiovascular pipeline (danicamtiv, ataciguat, tonlamarsen) | 📄 IPO Pricing and Terms Set

Parabilis priced its upsized IPO on June 10 at $20 per share, selling 33.5M shares for $670M in gross IPO proceeds. The stock opened at $33.35 on its first trading day, a 67 percent gain over the IPO price. Parabilis trades on Nasdaq under the ticker PBLS. The company is the rebranded FogPharma, founded by Gregory Verdine of Harvard and led by Mathai Mammen, the former CSO of Johnson & Johnson (JNJ). The $670M raise is the largest VC-backed biotech IPO on record, eclipsing Kailera Therapeutics ($625M, May 2026) and Moderna’s 2018 IPO ($604M). Concurrent with the offering, Regeneron (REGN) closed on a $75M private placement at $18 per share, bringing total proceeds to roughly $745M. The $75M equity check was the execution of Regeneron’s previously committed equity tranche from the May 18 collaboration, which included $50M upfront plus a $75M equity commitment under the broader $2.3B antibody-Helicon conjugate deal. Lead asset zolucatetide is a beta-catenin Helicon peptide targeting desmoid tumors with Phase 3 enrollment planned for H1 2027.

Kardigan set IPO terms on June 11 to raise up to $373M by offering 23.3M shares at a $14 to $16 range, targeting a $1.4B valuation. The pipeline covers danicamtiv (cardiac myosin activator for genetic dilated cardiomyopathy, Phase 2b/3), ataciguat (sGC activator for calcific aortic valve stenosis, Phase 2b), and tonlamarsen (antisense oligonucleotide targeting hepatic angiotensinogen for treatment-resistant hypertension, licensed from Ionis). The 2026 biotech IPO market has now produced more than a dozen offerings, with median raises above $300M, roughly 2x the 2025 median.

🧠 BPS Take: A $670M raise with an upsize and a 67 percent first-day pop tells you the institutional book was massively oversubscribed at the IPO price, which means bankers left money on the table and the buy-side was hungry.

Underneath all that is a thematic note of interest that could carry-through to more large rounds in the future: drugging the undruggable. That concept is having a moment, buttressed by the daraxonrasib PDAC data, showing that KRAS, which was once thought to not be druggable, is in fact a druggable target. The Helicon peptide platform appears to be a credible attempt at drugging undruggable intracellular targets like beta-catenin. Pair that with a late-stage asset entering pivotal studies and a relatively short line of sight into a commercial program, and you have yourselves a massive fundraising event in Oncology. Other companies who can credibly show movement on once untouchable targets with clinical data to back it up (whether it be with the help of AI, a novel platform, or some other means) will likely also see a big pot of gold coins for them at the end of the rainbow.

It will be interesting to see how Kardigan fairs when the final numbers come in for its IPO. My guess is they will do well too, given that they have multiple late-stage assets, both balancing risk and optimizing upside, plus a team that “has done it before” with the MyoKardia connection. The consistent theme across most of the large IPOs we have seen throughout this year has been the existence of validated mid-to-late-stage data. I don’t see that changing anytime soon. IPO markets are open if you have the clinical data to back it up.

GSK’s Biggest Deal Ever: $10.6 Billion for Nuvalent Bets the House on Next-Gen Lung Cancer

📅 June 9 | 🏢 GSK ( ) + Nuvalent ( ) | 💊 zidesamtinib (NVL-520) + neladalkib (NVL-655) | 🏷 M&A Acquisition

GSK announced an agreement to acquire Nuvalent for $10.6 billion, or $124 per share in cash, representing a 40% premium to Nuvalent’s last closing price and a 26% premium to its 30-day volume-weighted average price. The deal is expected to close in Q3 2026, subject to regulatory approval. This is GSK’s largest acquisition in its corporate history.

Nuvalent’s lead assets are two next-generation kinase inhibitors for non-small cell lung cancer. Zidesamtinib (NVL-520) targets ROS1-positive NSCLC and has a PDUFA date of September 18, 2026. Neladalkib (NVL-655) targets ALK-positive NSCLC and has a PDUFA date of November 27, 2026. Both drugs were specifically designed to overcome acquired resistance to current standard-of-care agents, including Pfizer’s lorlatinib and earlier-generation crizotinib. The pipeline also includes NVL-330, a Phase 1 HER2 inhibitor for NSCLC.

🧠 BPS Take: GSK is paying a 40% premium for two drugs that both have FDA decisions within six months of close, giving them two immediate new inline commercial assets to market in two very competitive spaces. The success or failure of this deal will hinge on the commercial performance of Nuvalent’s ALK and ROS inhibitors. The resonance of the differentiation story, being able to be a more mutation-resistant way of targeting these well-validated driver mutations, adding CNS penetrance to the equations to target brain mets, and with improved tolerability compared to existing options as a third/fourth-to-market offering will have to carry the day. Expansion into earlier lines of therapy will be key as well to expand the total addressable markets of these two drugs. On the surface, $11B for these set of drugs feels like a lot, but we should wait to judge until we see the commercial traction.

On a different level, this tells you that there is Big Pharma interested in better versions of validated targets (so called “me-betters”) if the data package is robust enough.

On a separate note, new GSK CEO, Luke Miels, has been an active acquirer since taking over the helm of the company. This Nuvalent deal is his largest yet, and pairs nicely with GSK’s B7-H3 ADC asset in Lung cancer. This deal also continues GSK’s slow re-entry back into Oncology, after largely exiting the space back in 2015. The company now has some niche commercial assets in JEMPERLI, BLENREP, OJJAARA, and ZEJULA but has clearly eyed Lung Cancer as its next frontier.

Roche Pays Nurix $700M Upfront, Up to $2.3B Total for Bexobrutideg

📅 June 8, 2026 | 🏥 Roche (RHHBY) and Nurix Therapeutics (NRIX) | 💊 Bexobrutideg (NX-5948), brain-penetrant oral BTK degrader | 📄 Exclusive Licensing and Co-Development/Co-Commercialization Agreement

Roche licensed bexobrutideg from Nurix for $700M upfront with up to $2.3B in total deal value across development, regulatory, and sales milestones. Development costs split 60 percent Roche and 40 percent Nurix. US commercialization is co-commercialized with profits and losses split 50/50. Outside the US, Roche commercializes with Nurix receiving low to high teens royalties. The asset is an orally bioavailable, brain-penetrant BTK degrader (not inhibitor) that eliminates both kinase and scaffolding functions of BTK, with the mechanistic claim that it overcomes resistance mutations that defeat current BTK inhibitors. Phase 3 initiation is planned for summer 2026 in second-line CLL. The deal scope spans B-cell malignancies, chronic spontaneous urticaria in immunology, and multiple sclerosis in neurology. Roche cited NHL plus CLL market projections of $41B by 2031 with BTK class at approximately $19B.

🧠 BPS Take: The deal terms here are fairly standard and this feels like a strong way for Nurix to monetize its key lead asset with an established commercial player. Multiple Sclerosis and CLL are two spaces Roche knows well and this deal speaks to me as a maneuver guided at fortifying the long-term stability of the company’s commercial prospects in those two diseases.

Still there is inherent risk with this mechanism of action in both of the major areas Roche is looking to achieve commercial success in. CLL is really damn competitive. You still have a multitude of on-market BTK inhibitors to contend with that are rather well-tolerated and used chronically. Roche and Nurix will need to make the case to switch to a degrader as the move into earlier lines of therapy, touting the longer-term BTK suppression that may be immune to resistance mutations, while also competing with degraders from other players like Lilly and BeOne.

On the MS front, BTK data to date has been rather mixed. German Merck’s evobrutinib, completes whiffed in its MS studies. Sanofi’s tolebrutinib also had mixed data that resulted in an FDA rejection. However, Roche’s own BTK inhibitor, fenebrutinib, has proved to be successful here, and will enter the market as a potential class-leader. The addition of bexobrutideg feels like Roche repeating its strategy with RITUXAN, GAZYVA, and OCREVUS — using RITUXAN as an anchor CD20 mAb and building towards next-generation versions in GAZYVA and OCREVUS. While OCREVUS turned out to be a commercial success story in MS, GAZYVA never really gained much traction in CLL, somewhat suffering from the high bar RITUXAN had already set. How Roche manages their two BTK offerings now in the wake of their experience with the CD20 programs it once juggled will be key to monitor.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

Frontline (1L) lung cancer always gets a ton of attention. It is arguably the single most important indication set in all of the KEYTRUDA (pembrolizumab; pembro) indications, allowing it to become one of the greatest therapeutics of all time.

1L NSCLC took center stage once again at ASCO 2026. All eyes were focused on Akeso and Summit’s HARMONi-6 data readout, studying the leading PD-1xVEGF bispecific antibody, ivonescimab (ivo), head-to-head vs. pembro in 1L NSCLC. Many caveats with this study hold, most notably that it is a China-only study. Frankly that caveat applies to a lot of the PD-(L)1 x VEGF class, as many of the leading programs being taken forward by US/EU developers originally came from China.

Summit is running a sister global study called HARMONi-3 studying ivo against pembro in squamous (~30% of NSCLC, typically older patients, worse prognosis, more smoking-driven) and non-squamous (~70% of NSCLC, typically younger patients, better prognosis but still bad, less smoking-driven) 1L NSCLC in separate cohorts.

The anticipation around HARMONi-6 is because it has read-through to HARMONi-3. That’s the case for BioNTech and Bristol-Myers’ pumitamig as well, which originally came from Chinese Co Biotheus. Though BNTX actually presented global data from the P2 portion of the P2/3 Rosetta LUNG-02 study at ASCO, examining pumitamig + chemo in squamous and non-squamous 1L NSCLC.

The same thing can also be said for Sacituzumab tirumotecan (sac-TMT, TROP2 ADC) from Merck and their Chinese partner, Kelun Biotech, which presented interim Phase 3 data from the OptiTROP-Lung05 study at ASCO.

While HARMONi-6 captured more attention, getting a prime viewing slot as a late-breaker, I actually though the Sac-TMT data looked more promising. Maybe its just the buzz associated with the PD-1xVEGF class and all the deal activity we’ve seen in that space, contrasted with the ups and downs the TROP2 class that has been weighing it down.

The outside world tends to look at competition largely through an in-class lens. Not always, but most of the time. PD-1s get compared to PD-1s. PD-1 x VEGFs get compared to PD-1 x VEGFs. CD19 CAR-T gets compared to CD19 CAR-T…and so and so on.

That’s a helpful angle when you’re comparing several companies and you want to get a better read or refine your thesis on whose stock will win out in that space.

Inside the walls of BioPharma, program teams take a much wider aperture. You are not only directly competing with the drugs in your class, you are also directly competing with drugs outside of your class. Doctors and patients don’t make treatment decisions in a within-class vacuum. Every possible option for your disease in your line of therapy is being considered.

So when we think about PD-1xVEGF in lung cancer, we also need to apply that broader lens, and consider out-of-class options that could steal prescriber share from them. After ASCO, its my belief that Sac-TMT is the one to watch out for for the entire PD-(L)1 x VEGF class going after NSCLC.

Let’s start by looking at a comparison of the data presented at the conference. In the gallery below I put together a side-by-side of the two China-only data sets presented by Kelun and Akeso on Sac-TMT and IVO respectively. I also threw in the P2 global data presented by BioNTech.

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

Daraxonrasib steals the show at ASCO, Otsuka leaves room for competitors in IgAN, a potential new market opportunity for CAR-T, another big longevity company raise, and much more.

All that and more below. Let’s get into it!

A little programming note: This edition of LWTB went out a little earlier than normal. I have a backlog of ASCO data I need to get through for some paid posts I am working on, so I wanted to get LWTB out to you sooner rather than later. Stay tuned for some ASCO deep dives if you’re a paid subscriber.

📡 PRESS RELEASE DECODER

What the press releases actually mean

Revolution Medicines Presents the Full RASolute 302 Dataset at ASCO: Daraxonrasib Cuts Death Risk 60% in Pancreatic Cancer, the Deadliest Solid Tumor in Oncology

📅. May 31, 2026 | 🏢. Revolution Medicines ($RVMD) | 💊. daraxonrasib (RMC-6236) | 🏷. Phase 3 Full Data Presentation (ASCO 2026 Plenary)

Revolution Medicines presented the complete RASolute 302 Phase 3 dataset at the ASCO 2026 plenary on May 31, delivering the most detailed look yet at daraxonrasib’s survival advantage over chemotherapy in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). The headline numbers from the April topline release were confirmed and expanded: median overall survival of 13.2 months versus 6.7 months for chemotherapy, with a hazard ratio of 0.40 (p<0.0001). That hazard ratio means patients on daraxonrasib had a 60% lower risk of death. (n=500 total: 248 daraxonrasib, 252 chemotherapy, confirmed from ASCO plenary press release)

🧠 BPS Take: The daraxonrasib data was just as good as everybody hoped: near doubling of overall survival in pancreatic cancer, where literally absolutely nothing works. I’ve lauded the Revolution Medicines team multiple times before on BPS, so I won’t recapitulate any of those comments here.

I saw a lot of commentary about how there was a standing ovation in the plenary session when these data were presented. That is such a monumental and moving acknowledgment of transformational science. What’s perhaps an even better biomarker, so to speak, of the impact of these data is when people outside of biotech and pharma are prompting you to talk about it.I’ve already had several of my non-biotech friends and family bring this dataset up to me, separately. I think that’s a real signal that this is going to be a majorly transformational drug, but commercially, RVMD has a lot of public momentum on their side.

As I’ve mentioned before, RVMD is, at this juncture, too big to be bought. They’re more likely to grow into the next Alnylam or even the next Vertex and become an acquirer themselves. The strategic angle that I didn’t fully appreciate until listening to interviews with the RVMD CEO was that there is potentially a much broader label than what people were once considering for this approval. The study looked at KRAS-G12D-specific patients, but also looked at patients with a much broader array of KRAS mutations, including wild-type KRAS. And notably, the broader population performed just as well as the KRAS-G12D-specific patient population.

I think RVMD is going to push for a broad second-line label in PDAC post chemotherapy. They might not get any restriction as to specific mutations, or they might end up landing at just “mutant KRAS” specific patients. Over 90% of PDAC is driven by KRAS, so it is conceivable to me that taking into account that this drug has a CNPV, has already had its expanded access program green-lit, has tremendous positive news coverage, that they will get a much broader label than just mutant KRAS G12D patients.

All signs point to daraxonrasib pioneering what is set to be a very large class of medicines, not just for pancreatic cancer, but likely for other mutant KRAS-driven solid tumors. The natural next question is: if RVMD is too big to buy, who else are they competing with that could be an interesting acquisition target, potentially improving on the clinical profile of daraxonrasib? Erasca is a name that keeps popping up and is one to watch.

Too soon? Tip me.

Ivonescimab Posts a 34% Death Risk Reduction in Lung Cancer at ASCO - Stock Gets Killed After Discussant Tears It Down

📅. June 1, 2026 | 🏢. Summit Therapeutics ($SMMT) and Akeso (6554.HK) | 💊. ivonescimab (AK112) | 🏷. Phase 3 OS Data Presentation (HARMONi-6, ASCO 2026 Plenary)

Summit Therapeutics and Akeso presented full overall survival data from the HARMONi-6 Phase 3 trial at the ASCO 2026 plenary. The trial tested ivonescimab, a PD-1 times VEGF bispecific antibody, against tislelizumab (BeiGene’s ($BGNE) PD-1 inhibitor) plus chemotherapy in first-line squamous non-small cell lung cancer (NSCLC). The result: a hazard ratio of 0.66 (95% CI: 0.50-0.87, p=0.0017), a median OS of 27.89 months for ivonescimab versus 23.69 months for the comparator, and a 24-month OS rate of 64.7% versus 48.6%. Summit filed an 8-K on June 1 disclosing the data.

🧠 BPS Take: If you were following the social media reaction to HARMONi-6, you probably saw the ASCO discussant, Dr. Julie Brahmer, point out several flaws in HARMONi-6 that muddy or at best narrow the interpretation of the results. I’ll summarize her main points here in case you missed it:

• Data was in Chinese patients only, so translatability to a global population is still TBD

• The study barely had any women in it (I don’t think she specifically made this one, but I saw several others make it)

• The control arm of tislelizumab + chemo isn’t the global standard. Tislelizumab is a chinese PD-1 and most global patients with 1L SQ NSCLC typically get pembro + chemo, which showed a median OS of 30-months in the China only Keynote-47 study. Basically she is saying maybe the control arm would’ve performed better, but most people think the China-only results for Pembro were kind of an outlier.

• The study protocol also excluded certain patients with major blood vessel invasion, significant tumor cavitation/necrosis, and significant hemoptysis. The issue here being that VEGFs carry a lot of bleeding risk, and these patients are more likely to be bleeders. Thus this could have been done to make the safety profile look a bit better, or clinically, it narrows the potential population you would consider for this drug.

• Study excluded patients who were over 75 years of age. The median age for lung cancer patients in the US is roughly 70 years old, so HARMONi-6 looked at a younger and potentially fitter population that is still less translatable to global or western populations.

So frankly, all her criticisms are fair and warranted. In fact, Summit’s stock tanked because of this, but that probably was a bit of an overreaction. The Summit data, despite all the caveats above were still quite strong and is evidence of an active and effective drug. They showed an OS benefit in squamous 1L NSCLC, where VEGFs have not done so well in the past and where the bleeding risk is naturally higher just given the histology of the disease vs. non-squamous.

Also, I felt like Brahmer was holding the study to a global standard, knowing that it was an entirely Chinese data set. No reasonable person went into this data readout thinking it would meet an FDA approvable standard. It was merely a peak into HARMONi-3, the study is going to use for US approval. Completely fair criticisms. Unrealistic expectations.

It does set up HARMONi-3 to be heavily scrutinized too. Summit will need to make sure they present clean data with sound design and no odd biostats shenanigans. I have my doubts that these China-only data sets are translatable to a global population. I’m also not sure that PD-1xVEGF is the 1L NSCLC class we should be looking at to dethrone pembrolizumab (more on that in a forthcoming paid post).

Otsuka’s VOYXACT Preserves Kidney Function Over 12 Months in IgAN. The APRIL Inhibitor Class Just Got Its Confirmatory eGFR Data

📅 June 4, 2026 | 🏥 Otsuka Pharmaceutical (TYO: 4578) | 💊 VOYXACT (sibeprenlimab-szsi), selective APRIL inhibitor | 📄 VISIONARY Phase 3 Interim eGFR Analysis. ERA Congress 2026

Otsuka reported pre-specified interim 12-month eGFR data from the global Phase 3 VISIONARY trial (n=320; sibeprenlimab n=152, placebo n=168) at the ERA Congress in Glasgow. Sibeprenlimab patients showed a mean eGFR change from baseline of +0.7 mL/min/1.73 m² (95% CI -0.9 to 2.3) versus -4.8 mL/min/1.73 m² (95% CI -6.3 to -3.3) in placebo, a treatment effect of 5.5 mL/min/1.73 m² (95% CI 3.4 to 7.6). Annualized eGFR slope was -3.0 mL/min/1.73 m²/year for sibeprenlimab versus -7.6 for placebo, a 4.6 mL/min/1.73 m²/year treatment effect. The on-treatment eGFR change met the KDIGO goal of bringing annual decline within the normal physiological rate of less than 1 mL/min/1.73 m²/year. Safety profile was comparable to placebo with infections (49 percent versus 45 percent) and injection site reactions (24 percent versus 23 percent) as the most common AEs. Otsuka has initiated a rolling sBLA submission to the FDA for traditional approval based on the 24-month eGFR endpoint. VOYXACT received accelerated approval on November 25, 2025 based on proteinuria reduction.

🧠 BPS Take: The eGFR data is the asset that converts VOYXACT’s accelerated approval into a traditional approval and locks in the commercial story. Accelerated approvals on proteinuria reduction in IgAN are how the modern wave of nephrology drugs has cleared the bar (Filspari, Tarpeyo, and now VOYXACT), but proteinuria is a surrogate. The hard endpoint that nephrologists, payers, and KOLs actually care about is whether the drug preserves kidney function over time, which is what determines whether a patient ends up on dialysis or transplant.

The -3.0 mL/min/1.73 m² slope at 12 months, is clinically meaningful, but potentially competitively weak. It leaves room for BAFF/APRIL inhibitors from Vertex and Vera to beat. Vera is gearing up for their own eGFR readout in Q3 of this year and has been a hot buyout target. Their P2b data showed a long-term eGFR slope that was basically flat, meaning normal kidney function.

It’s unclear whether Vera will hit that high bar in their P3 readout, but the -3.0 number posted by Otsuka came in lower than expected, giving Vera plenty of room to differentiate. If their data impress, that could be the trigger for buyout bids from bigger players.

🌎 CONNECTING THE DOTS

When the outside world meets biopharma

CAR-T Crosses Into Transplant Immunology. Two NEJM Papers Show CAR-T Can Make Functionally Non-Transplantable Kidney Patients Transplantable

📅 June 4 to 5, 2026 | 🏥 University of Pennsylvania (Ali Naji), German research team | 💊 CAR-T cell therapy for HLA desensitization in kidney transplantation | 📄 NEJM publications

Two research teams reported in NEJM on June 4 that CAR-T therapy successfully desensitized three highly HLA-sensitized kidney transplant candidates (two at Penn under Ali Naji, one in Germany), depleted donor-directed antibodies enough to enable transplantation, and all three patients went on to receive functional donor kidneys. Sensitization, driven by prior transfusions, pregnancies, or prior transplants, has historically rendered these patients functionally non-transplantable because their pre-formed antibodies reject most available donor kidneys. The desensitization approach uses anti-CD19 or CD19/BCMA constructs to deplete the B-cells and plasmablasts producing the donor-directed antibodies, then completes the transplant against a now-clean immune background.

🧠 BPS Take: I was very surprised to see this make it into Reuters. Let’s go CAR-T! The first half of the article is about this new transplant application, and the second goes into some updates with CAR-Ts in auto-immune conditions (which we know is continuing to become a bigger and bigger deal).

In the context of transplant, “sensitization” means the patient has already developed antibodies against the incoming foreign organ and there is a very high chance that it will get rejected. For this group of patients, finding a suitable transplant is incredibly difficult. Many of these patients looking for a kidney transplant spend years on dialysis because finding a suitable match that their body won’t reject is just too difficult.

So basically this approach, using a CD19 or CD19/BCMA CAR-T works int he same way that we see with CAR-Ts for autoimmune diseases. The CAR-Ts go in an deplete all your B-Cells (and in the case of BCMA your plasma cells too) and essentially “reset” your B-cell compartment so that the cells that were producing antibodies against the incoming transplant organ are gone. The CAR-Ts in a way help your B-cells “forget” that the organ is foreign so that it can be transplanted. Then chronic immunosuppressants can kick in and prevent long-term rejection.

The strategic question is whether autologous CAR-T is the right tool, or could you achieve the same results with a lower-cost and faster turnaround time options like in vivo CAR-T and allogeneic CAR-T. The market here could be reasonably sized. This study looked at the most sensitized patients and only for kidney transplants. Expand that to other organs (heart, lung, liver, etc.) and lower the sensitization threshold (let’s say down to 80%) and it could be amount to a reasonably sized orphan market opportunity that commands premium pricing. Beyond that there is tremendous value added back to the healthcare system by reducing dialysis utilization, reduced waitlist attrition, increasing the capacity of transplants, and also increasing the pool of potential compatible donor organs.

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💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Pfizer Licenses Chai-3 for Antibody Design and Alnylam Bets Up to $2B on Inceptive for RNA. Big Pharma Is Building a Modality-Specific AI Stack

📅 June 3 to 4, 2026 | 🏥 Pfizer ( ) plus Chai Discovery (private), Alnylam Pharmaceuticals ( ) plus Inceptive (private) | 💊 Chai-3 antibody design AI platform, Inceptive RNA generative AI platform | 📄 AI Discovery Platform Licensing Deals

Two AI platform licensing deals landed in 48 hours. Pfizer signed a license agreement with Chai Discovery for early access to the Chai-3 antibody design model plus a custom model trained on Pfizer’s proprietary data. Financial terms were not disclosed. Lilly (LLY) signed an essentially identical structure with Chai earlier in 2026, also receiving the base model plus a Lilly-data-trained custom build. Chai is OpenAI-backed and closed a $130M Series B at a $1.3B valuation in December 2025, with reporting from Forbes indicating it is in talks to raise another $400M.

The same day, Alnylam announced a three-year collaboration with Inceptive valued at up to $2B in milestones with $30M upfront in cash and equity. Inceptive builds generative machine learning models specifically for RNA biology, and the collaboration pairs that platform with Alnylam’s 20-plus years of RNAi data to design and prioritize next-generation RNA therapeutics. Inceptive was founded by Jakob Uszkoreit, a co-author of the original transformer architecture paper.

🧠 BPS Take: The two deals look superficially similar but tell different stories. Chai is slowly becoming the go-to antibody design vendor for Big Pharma. Pfizer and Lilly are now both on the same foundation model with custom layers trained on their proprietary data, which means the foundation model itself has commoditized at this layer and the competitive edge sits in the quality of the proprietary training data each pharma brings.

The Alnylam/Inceptive deal is the more strategically tailored bet. Alnylam is the global leader in RNAi, and Inceptive is one of the very few AI shops built specifically for RNA design rather than protein structure. Read more implicitly, this is Alnylam operating like a bigger player in the space, striking Big Pharma type AI collabs, but maintaining a clear focus within their core expertise.

NewLimit Raises $435M Series C as Aging Reprogramming Hits Its First Capital Inflection. Founders Fund Leads, Lilly Ventures Returns

📅 June 2026 | 🏥 NewLimit (private) | 💊 Liver-targeted epigenetic age reprogramming therapy (preclinical) | 📄 Series C Financing Close

NewLimit closed a $435M Series C led by Founders Fund with new investors Thrive Capital, Greenoaks, and Quiet Capital joining returning backers including Kleiner Perkins, Abstract, Nat Friedman and Daniel Gross, Valor Equity Partners, Eli Lilly Ventures, and Human Capital. The company plans to initiate its first human clinical trial in 2026 with a liver age reprogramming therapy designed to restore youthful function in aged hepatocytes via epigenetic reprogramming. The stated indications include faster liver healing after injury, protection from dietary challenge, and accelerated recovery from alcohol consumption. NewLimit was founded in 2021 by Brian Armstrong (Coinbase), Blake Byers (former GV), and CEO Jacob Kimmel.

🧠 BPS Take: NewLimit’s $435M sits next to Retro Biosciences’ recent $1.8B pre-money in the small group of longevity companies that are drawing in large sums of institutional capital, and the read across both rounds is the same. The groups that are writing the biggest checks to fund these huge longevity rounds are typically tech-first funds. This mix tends to make these roudns feel more like a SpaceX or OpenAI style growth round rather than a traditional biotech Series C. The investors are probably not thinking too critically about the clinical probability of success and doing deep scientific diligence. They are investing based on the “100x” opportunity and the credibility of the founding team.

None of that is a slight on NewLimit at all. Biotech is super hard. Take the most money you can from wherever you can get it. Use it wisely to take measured, but big swings, at transformational science. Unlike some other longevity focused biotechs who have kind of just been spinning their wheels for five years, burning through cash from their billionaire benefactors, and not really making any progress towards testing drugs in the clinic. NewLimit seems to be wired a bit differently. I give them a ton of credit for actually trying to make progress towards getting a drug approved.

NewLimit’s lead program, NLMT1001, looks to be targeting alcohol-associated liver disease. They appear to be starting here and may eventually look to expand into broader metabolic syndrome over time. I see the vision for this sequencing.

CytomX and Regeneron Expand 2022 Conditional Bispecific Collaboration. $37M Target Payment Now, $4B in Total Milestones, and Regeneron Gets Six More Shots on Goal

📅 June 3, 2026 | 🏥 CytomX Therapeutics ( ) and Regeneron ( ) | 💊 Conditional bispecific antibodies combining CytomX PROBODY masking with Regeneron Veloci-Bi bispecific platform | 📄 Collaboration Expansion

CytomX and Regeneron expanded their 2022 conditional bispecific oncology collaboration. CytomX gets a $37 million target nomination payment now for two additional programs that have been selected. Regeneron secures an option to select up to six additional future targets. Total potential value across target nomination payments and preclinical, clinical, regulatory, and commercial milestones could reach approximately $4 billion. Regeneron funds preclinical and clinical development and commercialization. CytomX is eligible for tiered global net sales royalties on covered products. The scientific premise is combining CytomX’s PROBODY masking, which keeps a biologic inactive until tumor-microenvironment proteases activate it, with Regeneron’s Veloci-Bi bispecific platform, with the aim of widening the therapeutic window for T-cell engagers in solid tumors that have been historically difficult for immunotherapy.

🧠 BPS Take: Regeneron has been working with PROBODY masking since 2022 and is now scaling to up to eight total targets, which says they have seen internal preclinical data clean enough to justify a multi-target platform commitment. That’s a big deal on its own, but an even bigger deal, given that Regeneron isn’t known to do a whole lot of partnerships or acquisitions. That implicitly signals real conviction from them.

T-cell engagers and bispecifics in solid tumors have seen many failures and hurdles due to both lack of efficacy and toxicity. However, conditional activation via tumor-specific proteases is starting to show some real signs of differentiation as evidenced players who possess masking platforms, like and .

The harder question is for CTMX shareholders. CytomX has a history of platform deals that produce milestone economics but not franchise economics (BMS walked in 2022, the AbbVie/ImmunoGen tie-up produced Varseta-M which CytomX still has to develop itself, Amgen and Moderna collaborations exist but have not yet produced visible clinical assets). This Regeneron expansion is the strongest external validation the PROBODY platform has, but it also reinforces the question of whether CytomX is best evaluated as a platform-out licensing company or as a product company.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

Lilly buys three vaccine platforms in a single day and drops some interesting gene-editing data, Pfizer locks in a China collab and subtly signals some retreat on their Seagen assets, and GLP-1s are finally on equal footing with US private insurers.

All that and more below. Let’s get into it!

A little programming note: I didn’t include any ASCO updates in this edition. I will be covering ASCO separately in future posts.

📡 PRESS RELEASE DECODER

What the press releases actually mean

Lilly/Verve’s VERVE-102 Cuts LDL Up to 62% With a Single Infusion — But the Real Question Is Whether Gene Editing Can Compete With Cheap Statins and Forthcoming Oral PCSK9s

📅 May 25-26, 2026 | 🏥 Eli Lilly ( ) / Verve Therapeutics | 💊 VERVE-102 (in vivo PCSK9 base editor) | 📄 Phase 1b Heart-2 Interim Data — EAS Congress Late-Breaker + NEJM Publication

Lilly reported positive interim Phase 1b Heart-2 data for VERVE-102, the in vivo adenine base editor designed to permanently turn off PCSK9 in the liver via a single IV infusion. In 35 patients with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease, a single dose produced dose-dependent mean PCSK9 reductions of 51–88% and LDL-C reductions of 9–62% across six dose cohorts (0.3–1.0 mg/kg), with effects sustained out to 18 months. No treatment-related serious adverse events, no dose-limiting toxicities, no withdrawals; the main AEs were low-grade infusion reactions and fatigue. '

The data were presented as a late-breaker at the European Atherosclerosis Society Congress and simultaneously published in NEJM.

The asset came to Lilly via its $1B acquisition of Verve, and Lilly plans to start Phase 2 by year-end 2026. VERVE-102 has FDA Fast Track designation for hyperlipidemia with high lifetime CV risk.

🧠 BPS Take: 60%+ LDL drop without background statins is impressive, but the real question for VERVE-102 is the competitive landscape it has to win against. The available PCSK9 mAbs (Repatha, Praluent) and forthcoming oral PCSK9 inhibitors achieve roughly the same LDL reduction on top of background statins, and statins are so cheap and so deeply entrenched in US prescribing that displacing them is structurally near-impossible. The PCSK9 mAbs underperformed initial expectations because of cost, prior auth friction, and injectable burden — issues that have improved with CV outcomes data, primary prevention indications, and price reductions, but that history is the cautionary template here.

Oral PCSK9s arriving over the next few years can tailwind off that mAb improvement and offer the same efficacy in pill form; dollar-for-dollar, oral remains the most likely class winner. Gene editing clearly works for LDL reduction, but the appetite from patients, prescribers, and payers for one-time treatment that delivers comparable efficacy to small molecules is “guilty until proven innocent”.

One aspect of in vivo base editing I did not fully appreciate though was the cost. Typically we think of in vivo gene therapies and gene editing drugs as being quite expensive, but the cost to make these therapies has come down quite a bit as a result of the massive scale up of mRNA and LNP supply chains during the pandemic.

Here’s Sek Kathiresan, CEO of Verve and noted dosa monger giving some insight into the manufacturing costs:

So at $5 per 100 microgram, that marks the the 1mg/kg dose in the study at roughly $4K for a 80KG adult. Now I don’t know if that number is just raw materials or if it includes labor, licensing, platform fees, royalties, etc. You always need to be a little cautious of COGS figures being floated out for programs that are still early-clinical stage. However, even at a $4K baseline, the cost is still starting lower than I would have expected.

I kind of buy this $5 number though because Lilly actually went in and cleaned up (to wit, bought out) a large chunk of the the licensing and royalties Verve would have owed to Beam (who they got the base editing tech from). Plus Verve is also using their own proprietary LNP for this program. The royalties and licensing is where the largest chunk of COGS stem from for mRNA-LNP based therapies. So the biggest piece of the COGS puzzle is likely pretty minimal for Verve/Lilly now, maybe still owing some small royalties to the original academic institution(s) the base editing tech comes from.

Not every company can really pull that off, so to me, it is still unclear if this COGS number is a Lilly-specific thing or far more uniform across other in vivo gene editing treatments. Either way, it feels like progress.

Sek has also subtly indicated that they are thinking about pricing this closer to common procedures a heart patient would get: things like stenting, coronary angioplasty, and catheter ablation. This means, you could see Lilly pricing their one-time gene-editing treatment at the $25-$50K range, which is way lower than what we typically associate with cell and gene therapies.

At that price point you start to really force payers and patients to think a little bit. It becomes a bit easier to pay for a $25K one-time treatment that can minimize your risk of getting a heart attack or stroke. That price tag starts to look a lot better than the roughly $6.5K per year you would pay for PCSK9 mAbs or siRNA.

Ultimately, I think the PCKS9 orals will be the initial commercial winner in this space. They get the same level of LDL suppression, with oral convenience, and map better to the formulary games insurance/PBMs like to play. Even those will need to sequence behind generic statins and ezetimibe. I would expect most patients and physicians to be initially slow to adopt a one-time gene-therapy in this setting and want to wait for long-term safety data to rule out any unexpected editing-driven toxicity. But after that, assuming all goes well, these one-time edits may make a better argument than any other competitors in the injectable class.

GSK's Bepirovirsen Hits 19% Functional Cure in Chronic Hep B Phase 3 — A 20x Improvement Over Standard of Care, and the First Real Shot at Replacing Lifelong Antivirals

📅 May 28, 2026 | 🏥 GSK ($GSK), licensed from Ionis Pharmaceuticals ( ) | 💊 Bepirovirsen (antisense oligonucleotide targeting HBV RNA) | 📄 B-Well 1 & B-Well 2 Phase 3 Results — NEJM Publication + EASL Late-Breaker

GSK reported positive pivotal data from the B-Well 1 and B-Well 2 Phase 3 trials of bepirovirsen, simultaneously published in NEJM and presented as a late-breaker at EASL. Pooled across both trials, a 6-month course of bepirovirsen achieved a 19% functional cure rate (233/1,220) vs. 0% on placebo plus standard of care (p<0.001 in both trials) in the overall population — adults with baseline HBsAg ≥3,000 IU/mL on nucleos(t)ide analogue therapy. In the pre-specified key secondary endpoint of patients with baseline HBsAg ≤1,000 IU/mL (~45% of diagnosed CHB cases globally), functional cure rose to 26% (200/768).

Functional cure is defined as undetectable HBsAg and HBV DNA in blood for at least 24 weeks after stopping all treatment. For context, current standard of care — lifelong nucleos(t)ide analogues — achieves functional cure in <1% of patients.

In exploratory analysis, 49% of bepirovirsen recipients reached qHBsAg ≤100 IU/mL one year after end of treatment, a level associated with improved long-term immune control. Safety profile was acceptable: the three most common AEs were injection site erythema, local pain, and transient liver enzyme elevations.

Bepirovirsen has FDA Priority Review with Breakthrough and Fast Track Designation; first regulatory decisions are expected Q3 2026. GSK announced a Sino Biopharmaceutical collaboration in May to accelerate China launch.

🧠 BPS Take: 19% functional cure may not sound like much, but it is a big moment in the HBV world, which has been a disease where cure rates have remained elusive. A 20x improvement over placebo is nothing to shrug your shoulders too in any disease.

Chronic Hep B affects 240M+ people globally (1.7M in the US, 75M in China) and accounts for ~56% of global liver cancer cases. The current paradigm is lifelong tenofovir or entecavir, which are effective at viral suppression but rarely curative, with the patient committed to indefinite therapy. Bepirovirsen offers a 6-month finite course that converts roughly one in five patients to off-treatment immune control.

It’s not the same was what we’ve seen in HIV or HCV, but it is still incredibly meaningful, and could be a first step towards renewed investment interest in this space that leads to more significant breakthroughs.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

CVS Caremark Re-Adds Zepbound and Unblocks Foundayo — All Three Major PBMs Now Cover Both Novo and Lilly Obesity Portfolios, Setting Up the First Real Oral GLP-1 Competition

📅 May 28, 2026 | 🏥 CVS Health / Caremark (CVS), Eli Lilly ( ), Novo Nordisk ( ) | 💊 Zepbound (tirzepatide), Foundayo (orforglipron), Wegovy (semaglutide) | 📄 Commercial Formulary Update

CVS Caremark announced two formulary changes that, taken together, reshape the GLP-1 obesity access landscape. Effective October 1, 2026, Zepbound (tirzepatide) returns to Caremark’s commercial template formularies as an additional preferred option alongside Wegovy — reversing the May 2025 exclusion that had handed Novo a single-payer advantage at the largest PBM in the country. Effective June 1, 2026, Caremark also removes the new-to-market block on Foundayo (orforglipron), Lilly’s oral GLP-1 approved on April 1, 2026.

With this move, all three major PBMs — Caremark (~88M lives), Express Scripts, and OptumRx — now cover both Novo and Lilly’s obesity franchises. LLY shares traded up as much as 6% on the news; this got remarkably little commentary across biopharma media given the scale of the access expansion.

🧠 BPS Take: For the past year, Caremark’s exclusion of Zepbound was the most consequential single payer decision in the GLP-1 class — it forced employer plans toward Wegovy by default and capped Lilly’s commercial upside. Reversing it sets up the first real head-to-head formulary competition in the obesity class on both injectables (Zepbound vs. Wegovy) and, more importantly, orals (Foundayo vs. an eventual oral semaglutide expansion).

Oral GLP-1 competition is the more interesting commercial battleground because orals are far more frictionless. CVS’s own framing , “delivering affordability and optionality”, after manufacturer negotiation is the polite way of saying both Novo and Lilly conceded net price to get on (or stay on) the formulary.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Pfizer Pays $650M to Option Into 12 Chinese ADC and Bispecific Programs

📅 May 28 | 🏢 Pfizer ( ), Innovent Biologics ( $IVBXF ) | 💊 12 ADC and multi-specific antibody programs | 🏷 Strategic Partnership | Up to $10.5B

Pfizer ($PFE) and Innovent Biologics announced a strategic collaboration covering 12 oncology assets, including eight Innovent-originated programs and four programs from Pfizer’s discovery pipeline. The deal terms provide for $650 million in upfront payments, with total potential value of up to $10.5 billion including development and commercial milestones. Under the structure, Innovent leads clinical development through Phase 1. Pfizer then holds rights to advance the programs globally outside of China, with tiered co-development and co-commercialization arrangements depending on the asset. Innovent shares rose approximately 10% on the announcement.

🧠 BPS Take: A few curious details in the press release worth highlighting. Pfizer gets global rights to 4 programs, ex-China rights to 4 other programs, and a global Co/Co on 4 other programs. The programs span multi-specific antibodies, but notably also ADCs. It’s a strange deal considering Pfizer spent $40B+ on an ADC company (Seagen) in 2023, with little to show for it. Implicitly, they are conceding that a lot of the pipeline Seagen assets were not good enough or will be deprioritized.

True co-commercialization arrangements between Big Pharma and Chinese biotechs remain rare — Legend Biotech / J&J on Carvykti (50/50 global cost-and-profit split outside Greater China; 70/30 in Greater China favoring Legend) is the canonical reference, and the comparable structures are few. Most recent US-China oncology deals have been structured as licensing or option deals with cleaner economic separation. I’m not sure how this is going to play with the current White House. However, amidst all the struggles Pfizer has had post-COVID, the one thing they have seemed to do a good job of is maintaining a friendly relationship with the Trump administration.

Eli Lilly Buys Three Vaccine Developers for $3.8B in a Single Day

📅 May 26 | 🏢 Eli Lilly ($LLY) | 💊 Shingles vaccine (Curevo), staph vaccine (LimmaTech), EBV vaccine (Vaccine Company) | 🏷 Triple M&A: Vaccine Acquisitions | $3.8B combined

Eli Lilly ($LLY) announced the acquisition of three private vaccine developers on May 26 in a combined deal valued at up to $3.8 billion. The three companies are Curevo, a shingles vaccine developer acquired for $1.55 billion, LimmaTech Biologics, a Swiss company developing a vaccine for staph infections, and a company referred to in press reports as Vaccine Company developing an EBV and mononucleosis vaccine.

The three acquisitions push Lilly’s 2026 total M&A spending past $20 billion. Earlier deals this year include the acquisition of Centessa Pharmaceuticals for $7.8 billion (orexin receptor agonist in sleep disorders, March 31), Kelonia for $7 billion (in vivo CAR-T platform, April 20), Ajax Therapeutics for $2.3 billion (JAK2 inhibitor in myeloproliferative neoplasms, April 27), and a deal for Profluent (gene editing, up to $2.25 billion in milestones, undisclosed upfront).

Curevo’s lead shingles vaccine would compete with GSK’s ($GSK) SHINGRIX, which generates more than $4 billion in annual revenue and is the dominant shingles vaccine franchise globally.

🧠 BPS Take: The hat trick of vaccine company deals are almost secondary to the meta-story, which is that Eli Lilly has spent what for most companies would be a decade’s worth of business development budget in a single calendar year, and every single acquisition is in a therapeutic area with no meaningful overlap with GLP-1 obesity and diabetes. This is Lilly trying to intentionally diversify for the long-term and set them selves up to be less dependent on GLP-1 revenues over the long-term, especially after they inevitably go generic.

You’re never going to plug that GLP-1 sized revenue hole with one product (at least that is unlikely), so spending the dollars while you have them to build into orthogonal opportunities is prudent risk-management and strategy.

Digging into the vaccine story a bit, it is a bit odd that Lilly went down this route, given they aren’t considered a typical vaccine company or a player in infectious disease. Still, this could be an area their corporate strategy team has identified as winnable (the hiring of former FDA vaccine chief Peter Marks says as much) and investing in three core platforms would allow Lilly to slowly build into being a player in this therapeutic area, which has largely been dominated by the likes of Merck, Pfizer, Sanofi, and GSK.

Kardigan Files S-1 With Three Mid-to-Late-Stage Cardiovascular Assets — MyoKardia 2.0

📅 May 27, 2026 | 🏥 Kardigan (pre-IPO) | 💊 Danicamtiv (cardiac myosin activator), tonlamarsen (ASO targeting hepatic angiotensinogen, licensed from Ionis), ataciguat (sGC activator, licensed from Sanofi/Mayo Clinic) | 📄 IPO S-1 Filing

Kardigan filed its S-1 on May 26, capping a remarkably fast 18-month arc from launch to public markets. The Bay Area cardiovascular company is led by CEO Tassos Gianakakos — who ran MyoKardia for seven years before its $13.1B sale to Bristol Myers Squibb in 2020. The company has raised approximately $570M to date across a $300M Series A (January 2025) and a $254M Series B (last fall). Cash position was $287.1M at the end of March.

The lead asset, danicamtiv, is a cardiac myosin activator (mechanistically the inverse of MyoKardia/BMS’s Camzyos, a myosin inhibitor) in Phase 2b/3 for genetic dilated cardiomyopathy, originally a BMS asset. Tonlamarsen is an Ionis-licensed antisense oligonucleotide targeting hepatic angiotensinogen for treatment-resistant hypertension; its prior Phase 2 readout hit a biomarker endpoint but missed the primary blood pressure endpoint. Ataciguat is a soluble guanylate cyclase activator licensed from Sanofi and Mayo Clinic, in Phase 2b for calcific aortic valve stenosis — an indication with no approved disease-modifying therapy.

🧠 BPS Take: The investment pitch here is pretty simple. Here is a company flush with cash that has collected three under-appreciated assets from (mostly) Big Pharma and are looking to remix the MyoKardia album, only this time with three hit songs instead of one. It also helps that you have a management team that has done it before, specifically in cardiovascular disease.

On the IPO market read: Kardigan joins Seaport, Hemab, Avalyn, Odyssey, Generate, and Kailera in a window that has clearly reopened, with the common thread being Phase 2+ assets and $250M+ raise targets. Investors are paying for de-risked clinical data (not platforms).

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

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Every industry is trying to get smart on AI, and BioPharma is no different.

Over the course of this year we have seen a slew of press releases outlining major partnerships between our sector’s major players and a cornucopia of AI-houses. These range all the way from tiny companies that are using AI to model biology and speed up drug discovery all the way up to the so called “frontier labs”.

This “frontier labs” group is what I wanted to focus on for this post. ChatGPT, Claude, and Google Gemini are probably the three most popular large language models (LLMs) the average person interacts with (sorry Grok 😢).

You probably use one of these to figure out recipes based on a picture of what is in your fridge, draft a polite email to an annoying vendor that keeps bugging you about how they can “bring you 5-10 new leads per week”, or to settle dumb debates with your partner, like whether the dishwasher actually requires pre-rinsing (it doesn’t…just buy better detergent) or if peanut butter should be stored in the fridge (that is overkill…plus it makes it way harder to spread and life is difficult enough).

Your favorite Big Pharma company is using one or two of these frontier models as well, but only for more complicated things.

AI is making its way into BioPharma one way or another. It’s here to stay. As I noted in a previous post, these Tech/AI companies are quickly running out of room to innovate in the realm of software. LLMs are based off of code and are really great at doing things that require coding, like developing software. They are built on code and understand code super well. Eventually massive swaths of that space are going to get commoditized, leaving AI to need to find greener pastures to graze. There is no greener pasture than advancing human health via novel therapeutics.

Given these AI companies are pervasive across our daily life and are going to be IPO’ing soon(ish) with massive valuations to give them even more momentum to make inroads with BioPharma, I wanted to take a look at who is partnering with who and for what purposes. What trends can we see? What insights can we glean, when we look at how Big BioPharma and Big AI are coupling up?

As of May 2026, I've tracked 27 confirmed strategic partnerships between frontier LLM providers and major Pharma companies, plus one company (GSK , more on them later) that has decided to build the whole thing in-house and tell the AI labs to kick rocks.

This dataset only tracks named partnerships with Anthropic, OpenAI, and Google Gemini. It does not include the broader AI footprint in our sector, which is massive. Recursion, InSilico, AbSci, NVIDIA compute deals, the various academic collaborations, and the dozens of internal data science teams running their own thing are all excluded unless they show up in a named LLM contract.

The actual AI surface area inside Pharma is much bigger than 27 deals. The focus of this exercise is to zero-in on the frontier AI models and how they are being used by the big companies.

The AI + Big Pharma Collaboration Landscape

Most of the top companies are using Anthropic/Claude in one way or another, with 52% share of the 27 deals I was able to find evidence of. Open AI is second with 11 deals (41%) and Google Gemini with just two deals, but notably one of them is with Merck with the largest disclosed value of $1B.

Six companies are not tying their fates to one horse, and are partnered with both OpenAI and Anthropic.

Only GSK sits alone, with no external LLM partnerships that I could find. Instead they seem to be building their own, called JulesOS, with the help of their own AI/ML engineers. I found this zag from GSK quite interesting. In their view, they see the advantage of build (vs. buy) as as mitigating clinical-risk hallucinations, safeguarding multi-billion dollar pre-clinical IP, and unlocking proprietary functional genomics datasets that public LLMs cannot access. We will see how this shakes out over time, but the fact that GSK built their own, while their competitors are working with the leading players, allows GSK to serve as somewhat of an active control group.

The functional distribution tells you where the field thinks LLMs actually work today. Unsurprisingly, 82 percent of these deals touch Research and Discovery in some form and then Clinical Development as the next most common functional area. I would have expected manufacturing/CMC to be more common, but there are only a handful of these partnerships that have disclosed manufacturing implementations.

Too soon? Tip me.

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week! Eli Lilly dropped bariatric-level Phase 3 obesity data for retatrutide that puts every competitor on notice, ASCO 2026 turned into a showcase for ADC data that reset the competitive calculus in multiple tumor types, and Regeneron placed a $2.3B bet on a new drug class that does not yet exist in any pharmacy.

Meanwhile, the institutional collapse of the U.S. regulatory and infectious disease infrastructure continued to accelerate in ways that should concern every biopharma executive with a PDUFA date in 2026 or 2027. All that and more below. Let’s get into it!

📡 PRESS RELEASE DECODER

What the press releases actually mean

Lilly’s Triple-G Retatrutide Posts Bariatric-Level Weight Loss in TRIUMPH-1

📅 May 21, 2026 | 🏢 Eli Lilly ( ) | 💊 retatrutide (LY3437943) | 🏷 Phase 3 Topline Data (Positive)

Eli Lilly reported topline results from TRIUMPH-1, the pivotal Phase 3 obesity trial for retatrutide, a first-in-class triple GIP/GLP-1/glucagon agonist. At the 12 mg dose, patients in the all-comers population achieved 28.3% mean body weight loss at 80 weeks, extending to 30.3% at 104 weeks. Topline results were released via press release on May 21, 2026, with the full data package to be presented at the ADA 2026 Scientific Sessions. TRANSCEND-T2D-1, the companion trial in patients with type 2 diabetes, is reading out alongside TRIUMPH-1.

The headline efficacy number that will define the retatrutide commercial narrative is this: 45.3% of patients on the 12 mg dose achieved 30% or greater body weight loss, a threshold historically associated with bariatric surgery outcomes. Retatrutide’s mechanistic differentiation from ZEPBOUND (tirzepatide), which targets GIP and GLP-1 only, comes from the added glucagon receptor agonism, a component hypothesized to drive the incremental weight loss above what dual agonism alone can deliver. ZEPBOUND achieved approximately 22% mean weight loss in the SURMOUNT-1 trial.

🧠 BPS Take: When we covered Novo Nordisk’s ($NVO) WEGOVY HD data out of ECO in the May 17 edition, the 28% weight loss figure came from early responders only, a pre-selected subgroup that represents a fraction of treated patients. Retatrutide’s 28.3% comes from an all-comers population, which is a stronger claim from a regulatory and commercial positioning standpoint.

While 30% weight loss (@ 104 wks) and 28% (@80 wks) are the headliners, both of those numbers come from the 12mg (max) dose. What I was more impressed by was the 4mg (lowest) dose, hitting 19% (@80wks).

I am curious to see the full data to learn how quickly that level was achieved. Remember these are patients who avg. 250 lbs at baseline in the study. In the real world that’s roughly the 90th percentile in the US.

As we know, by some measures at least ~40% of the US population is obese and up to ~75% are overweight. For a lot of these folks, losing 20% of BW (~40lb for a 200lb person) will be more than enough to see their desired health and aesthetic benefits.

My guess is the 4mg dose will be the best-selling dose-level of retatrutide.

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The bigger question for me is what this does to the tirzepatide franchise in the medium term. ZEPBOUND is currently Lilly’s obesity crown jewel, and retatrutide, if approved, will sit above it in efficacy. Lilly could opt to let reta completely cannibalize its ZEPBOUND business. And in fact Lilly is running a head-to-head study between the two products, called TRIUMPH-5.

But they could also opt to position ZEPBOUND for a slightly different customer groups (people looking to lose less weight less quickly, less tolerant of AEs, etc.) and price the two products differently, perhaps sandwiching Novo’s WEGOVY between them on price.

This would put huge squeeze on Novo’s business. You have a cheaper ZEPBOUND option with equivalent or greater efficacy and better safety on one end, and a powerhouse 30% weight loss premium product on the other.

Too soon? Tip me.

AstraZeneca Gets a FDA First-in-Class Win with BAXFENDY and a Regulatory Split Decision on Camizestrant in the Same Week

📅 May 18–22, 2026 | 🏢 AstraZeneca ( ) | 💊 BAXFENDY (baxdrostat) + camizestrant | 🏷 FDA Approval + EU CHMP Opinion + Regulatory Divergence

The FDA granted approval on May 18, 2026 to BAXFENDY (baxdrostat), making it the first aldosterone synthase inhibitor ever approved globally for uncontrolled hypertension. The drug works by blocking CYP11B2, the enzyme responsible for aldosterone production, offering a mechanistically distinct option in a condition that affects roughly 100 million Americans. AstraZeneca acquired baxdrostat through its $1.8 billion buyout of CinCor Pharma in 2023, and this approval represents the first first-in-class NME payoff from that deal.

In the same week, the EU’s CHMP issued a positive opinion for camizestrant, AstraZeneca’s next-generation oral SERD, in HR+/HER2- early breast cancer based on SERENA-6 data. Recall, three weeks earlier, on April 30, 2026, the FDA’s ODAC voted 6-3 against camizestrant’s benefit-risk profile, leaving AstraZeneca staring at a NDA resubmission decision.

🧠 BPS Take: The CinCor acquisition logic looks very good right now. $1.8 billion for a first-in-class mechanism in a 100 million patient market is not chump change, but the math starts to feel reasonable the moment you see that approval. Aldosterone-driven hypertension has been a known and underserved segment for years, and BAXFENDY gives AstraZeneca a differentiated cardiovascular franchise asset that does not have a direct approved competitor. Although companies like Mineralys are looking to change that.

The camizestrant situation is the harder story to tell. The EU-US divergence signals that the SERENA-6 data package reads differently depending on the evidentiary standards being applied, and the FDA ODAC’s 6-3 vote against benefit-risk is a fairly clear signal about what a resubmission needs to fix. AZ’s path with camizestrant in the US is narrowing fast. VEPPANU launched into the oral SERD category with first-mover advantage. Every month AZN delays a resubmission is another month VEPPANU is building prescriber relationships and formulary positioning in the US without a competitor.

The bigger question for me is whether AZN believes a resubmission is winnable on revised data or whether the resources are better deployed elsewhere in the oncology portfolio. The EU approval buys some commercial optionality outside the US, but the American market is where the oral SERD war will actually be decided.

sac-TMT Posts Dual OS and PFS Win in TROP2

📅 May 21-22, 2026 | 🏢 Merck ( ) + Kelun-Biotech ( $KLUN.SS ) | 💊 sacituzumab tirumotecan (MK-2870) / | 🏷 Phase 3 Readout

Merck and Kelun-Biotech dropped two headline Phase 3 readouts for sacituzumab tirumotecan (sac-TMT, MK-2870) at ASCO 2026 on May 21. In TroFuse-005, sac-TMT became the first TROP2-targeting ADC to demonstrate improvement in both overall survival and progression-free survival versus chemotherapy in patients with advanced or recurrent endometrial cancer. That OS signal is the landmark here. TROP2 ADCs have accumulated PFS data before, but a clean dual-endpoint win in a gynecologic solid tumor is a new bar for the class. Merck says these data will be presented at a future meeting.

The second readout, OptiTROP-Lung05, evaluated sac-TMT in first-line non-small cell lung cancer in Chinese patients and produced a PFS hazard ratio of 0.35 versus KEYTRUDA (pembrolizumab) alone, representing a 65% reduction in progression or death risk. Kelun reported that median progression-free survival (PFS) has not yet been reached in the sac-TMT patient group, compared to a PFS of 5.7 months for the anti–PD-1 mAb (p< 0.0001). Full data are set to be shared at ASCO in the coming days.

Merck is running a global P3 study, called TroFuse-007 in 1L PDL1-high NSCLC, which these ASCO data will have significant read-through to.

🧠 BPS Take: The Sac-TMT data continue to look stronger and stronger, posing a real threat to Gilead’s TRODELVY, which has never been able to meet the sales expectations set by the $21B acquisition of Immunomedics.

Gilead’s TRODELVY has not posted a clean OS win in a Phase 3 outside of breast cancer. AstraZeneca’s DATROWAY is in a similar position. Between the two products, they’ve registered six failed P3 studies. Sac-TMT on the other hand, has had a spotless record, and these two new topline data readouts continue to brighten the shine coming off this molecule.

Merck may have cracked the code on TROP2 ADCs. They have an aggressive P3 program built behind Sac-TMT, because they feel they have a best-in-class product that is up against floundering competitors. Going where TRODELVY and DATROWAY could not, in lung cancer, both 1L as well as EGFR-mutant, appears to be the initial play, followed by expansion into breast cancers and other gynecologic tumors.

The threat doesn’t stop at TROP2 ADCs either. The NSCLC 1L data set to be presented at ASCO, should stop the PD1xVEGF companies who have in-licensed Chinese bispecifics in their tracks as well. When you compare the Sac-TMT readout to Summit and Akeso’s China-only data of ivonescimab, the Sac-TMT looks quite a bit better across both safety and efficacy. The same translatability concerns of China-only data to a global population apply, but just on a China-to-China basis, it is hard to ignore how strong OptiTROP-Lung05 looks relative to PD-1xVEGF.

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GLP-1s Cut Metastatic Progression Up to 50% Across Four Obesity-Related Cancers — But the Comparator Choice Is Already Under Fire Ahead of ASCO

📅 May 21, 2026 | 🏥 Cleveland Clinic / Taussig Cancer Institute | 💊 GLP-1 RAs vs. DPP-4 inhibitors | 📄 ASCO 2026 Abstract 3143 (pre-meeting press briefing)

Ahead of next week’s ASCO Annual Meeting, Cleveland Clinic investigators led by Dr. Mark Orland released real-world data suggesting GLP-1 receptor agonists may meaningfully reduce metastatic progression across several obesity-related cancers. The story made its way into the lay press.

Using the TriNetX network, the team ran a propensity-matched retrospective analysis of 12,112 Stage I–III patients who initiated either a GLP-1 (semaglutide, tirzepatide, liraglutide, dulaglutide) or a DPP-4 inhibitor after diagnosis, matching on BMI, glycemic factors, smoking, comorbidities, oncologic treatments, and concurrent medications. Statistically significant reductions in progression to Stage IV were observed in four of seven tumor types: NSCLC (10% vs. 22%), breast (10% vs. 20%), colorectal (13% vs. 22%), and hepatocellular carcinoma (19% vs. 28%). Prostate, pancreatic, and renal cell trended favorably but missed significance. A separate TCGA analysis found high tumor GLP-1R expression was associated with a 33% lower risk of death across the seven types, and 45% lower in breast specifically.

🧠 BPS Take: I’ll withhold judgment until I see the full ASCO data. However, there are some obvious caveat here with this being an observational study. The comparator is already contested. Dr. Jiang Bian (Indiana University), whose group published a related Medicare-claims analysis in Obesity in 2025, has noted that when GLP-1s are benchmarked against SGLT2 inhibitors rather than DPP-4s, the cancer benefit disappears.

Smarter minds than me can argue about the specifics, but the broader point here is that the benefits of GLP-1s may continue to accrue into unexpected areas like cancer. This study isn’t definitive by any means, but could sever as sufficient signal for academic groups to study GLP-1s as cancer prevention agents. A natural next step would be testing GLP-1s in patients in the adjuvant setting, perhaps in earlier stage tumors, to see if GLP-1s extend relapse free survival.

For now, there isn’t much for Lilly or Novo to act on, but these data may the first step towards a potential new indication for GLP-1s.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Regeneron Bets $125M Upfront and Up to $2.3B on Parabilis’s Helicon Peptides to Crack Undruggable Targets, Then Parabilis Files a Massive IPO

📅 May 18-19, 2026 | 🏢 Regeneron Pharmaceuticals ( ) + Parabilis Medicines (pre-IPO) | 💊 Helicon Peptide Platform / Antibody-Helicon Conjugates (AHCs) | 🏷 Strategic Collaboration + IPO S-1 Filing

On May 18, Regeneron ( ) announced a strategic collaboration with Parabilis Medicines built around Parabilis’s proprietary Helicon platform, which produces stabilized cell-penetrant alpha-helical peptides designed to reach intracellular and historically undruggable protein targets. The financial terms were anything but subtle: $50M in upfront cash plus a $75M equity investment, totaling $125M before a single milestone is triggered, with up to $2.3B in additional milestone payments attached. The collaboration is structured to combine Regeneron’s antibody engineering capabilities with Parabilis’s Helicon peptides to produce a new drug class called Antibody-Helicon Conjugates, or AHCs. Parabilis’s own lead program targets desmoid tumors, a rare and notoriously difficult-to-treat soft tissue cancer.

Then, one day later on May 19, Parabilis filed an IPO S-1. The company had already raised approximately $800M in total private capital, including a $305M Series F in January 2026, making it one of the most heavily capitalized pre-IPO biotechs in recent memory. IPOScoop estimates the offering could rank as 2026’s largest biotech IPO.

🧠 BPS Take: Anytime Regeneron does a deal you have to take notice. This is because they don’t do a whole lot of them, and typically rely on internal innovation fare more than external. There is clearly something they see in Parabalis that they can’t do themselves. Fusing antibody-targeting with peptide payloads to create a brand new class of medicines could be a major step forward in the druggability of targets.

The deal structure is notable too, with Regeneron taking on $75M of equity in Parabalis. Filing an S-1 the morning after a $75M investment from one of the leading Big BioPharma players is also a very deliberate move, and any institutional investor picking up that prospectus is reading it with very different eyes than they would have 48 hours earlier. Regeneron’s name carries a lot of weight and the reputation of being a science-first company. Investors look at this an see less risk in this brand new class of medicines knowing that Regeneron has co-signed this platform and taken equity in the company.

Retro Biosciences Closes at $1.8B Pre-Money on Altman-Backed Longevity Thesis — Alzheimer’s Autophagy Readout in August Is the Real Catalyst

📅 May 22, 2026 | 🏥 Retro Biosciences (pre-IPO) | 💊 RTR242 (oral autophagy activator) + cell therapy + iPSC + AI protein engineering platforms | 📄 Financing Announcement — Initial Close Led by 4P Capital

Retro Biosciences, the Sam Altman-backed longevity company, announced the initial close of its latest financing round at a $1.8 billion pre-money valuation, led by 4P Capital. The round lands the company firmly in the upper tier of private longevity biotechs at a time when institutional capital has grown notably selective about the category.

Retro’s stated mission, adding 10 healthy years to human lifespan, is being pursued across four parallel platforms: a small-molecule autophagy program (lead asset RTR242), autologous iPSC-derived hematopoietic stem cell therapy via a partnership with the Murdoch Children’s Research Institute, in-house cGMP cell therapy manufacturing, and AI-enabled protein engineering.

RTR242, a first-in-class oral therapeutic designed to restart cellular autophagy, moved from indication selection to first-in-human dosing in 15 months and is now enrolling Alzheimer’s patients in Phase 1, with CEO Joe Betts-LaCroix telling STAT’s Breakthrough Summit West that no dose-limiting toxicities have been observed and that initial data is expected around August 2026.

🧠 BPS Take: A $1.8B valuation is massive, especially for a cmopany that has no clinical data to speak of yet. But this is part for the course for longevity companies with major tech CEO backing. The fact that Retro did not disclose the actual amount they raised or additional investors beyond their lead investors is also may indicate a sizable chunk of the investment coming from private individuals who may not want ot be named.

At the STAT News summit in San Francisco, Retro’s CEO noted that they are awaiting a clinical readout for RTR242. He mentioned that the drug looks safe and that they are continuing to escalate the dose to get to the maximum and see if any toxicity pops up. It’s good that there is no initial safety signal, but I would have some pause that they haven’t seen any tox yet and need to continue raising dose. As we know in the drug development world, the reason you arent’ seeing any AEs could be because your drug isn’t doing anything. We will need to see some sort of biological signal of protein aggregate clearance too in the full update.

Longevity companies remain a weird outlier in BioPharma. They all have massive valuations for little more than cool science at this point. I am hopeful we start to see real clinical signal coming from one or more of these shops, to graduate them to being actual drug developers and not just science projects for tech billionaires.

Worth flagging that RTR242’s autophagy mechanism is meaningfully differentiated from the amyloid-targeting antibody class (Leqembi, Kisunla) that currently defines Alzheimer’s therapeutics. Alzheimer’s is in major need of new MOAs beyond amyloid beta and tau targeting:

If the August data update shows some biological signal, that would be a nice first (small) step for Retro and the broader Alzheimer’s field.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful. Safe travels to ASCO if you are headed Chicago!

Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

This week, BMS wrote a $600M check to Hengrui as part of a staggering $15.2B China licensing deal. Novo dropped new obesity data showing high-dose WEGOVY hitting 28% weight loss in a group of fast-responders, but could this data actually speak to a long-term trend in obesity that backfires against Novo and Lilly? Meanwhile, BeOne get's its BCL-2 inhibitor BEQALZI across the FDA finish line for relapsed or refractory mantle cell lymphoma. Oh, and the FDA’s entire top-level of leadership got the axe.

All that and more below. Let’s get into it!

📡 PRESS RELEASE DECODER

What the press releases actually mean

FDA Grants Accelerated Approval to BeOne’s BEQALZI (sonrotoclax) for R/R Mantle Cell Lymphoma

📅 May 13, 2026 | 🏢 BeOne Medicines ( ) | 💊 BEQALZI (sonrotoclax) | 🏷 FDA Accelerated Approval

The FDA granted accelerated approval to BeOne Medicines’ ($ONC) BEQALZI (sonrotoclax) for relapsed or refractory mantle cell lymphoma (R/R MCL) on May 13, making it the first and only BCL-2 inhibitor cleared in this indication. The approval marks the 14th novel drug FDA has approved so far in 2026, per the agency’s running tally.

Sonrotoclax is a next-generation BCL-2 inhibitor designed to address some of the resistance mechanisms and tolerability issues seen with venetoclax (AbbVie’s ($ABBV) VENCLEXTA). BeOne’s press release framed this as validation of its hematology pipeline following its high-profile rebrand away from the BeiGene name, a move designed to reposition the company’s U.S. commercial identity amid ongoing geopolitical scrutiny of China-linked biotechs.

MCL is a rare and aggressive B-cell lymphoma with limited options after BTK inhibitor failure. The accelerated approval pathway means BeOne will need to confirm clinical benefit in a post-marketing confirmatory trial, but the commercial window is open now. Reuters noted that this positions sonrotoclax directly against the venetoclax franchise, which generated over $2.5 billion in sales last year across indications for AbbVie and its collaboration partner Roche/Genentech.

🧠 BPS Take: The AbbVie/Genentech venetoclax franchise is a $2.5B-plus-per-year business built largely on CLL and some AML sales that has faced no in-class challengers. Venetoclax is an effective drug, but requires a 5-week dose ramp up to minimize the risk of tumor lysis syndrome (TLS). Sonrotoclax has been designed with a much cleaner profile and more refined chemistry. Sonrotoclax landing in MCL first is a smart foot-hold securing move, enabling BeOne to play in an indication where venetoclax has no market presence as they build into the much larger CLL opportunity. Sonrotoclax is already approved in China in both CLL and MCL and BeOne has four Phase 3 studies in CLL ongoing to be used to file in western markets.

Novo Nordisk Drops an "Early Responder" Analysis at ECO. The Real Target? Eli Lilly.

📅 May 12 | 🏢 Novo Nordisk ( ) | 💊 WEGOVY HD (semaglutide 7.2 mg) | 🏷 STEP UP Sub-Analysis (ECO 2026)

Novo Nordisk ($NVO) presented new sub-analyses from the STEP UP trial at the European Congress on Obesity (ECO) in Istanbul this week, highlighting weight loss outcomes with WEGOVY HD (semaglutide 7.2 mg) stratified by speed of initial response.

The STEP UP trial enrolled 1,407 adults with obesity (BMI ≥30, no type 2 diabetes) and ran for 72 weeks, double-blind, with three arms: semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo. The primary results, already published in The Lancet Diabetes & Endocrinology, showed 20.7% mean weight loss on the 7.2 mg dose, 17.5% on 2.4 mg, and 2.4% on placebo.

The new sub-analysis introduced an “early responder” classification: patients who lost 15% or more of body weight by week 24. On the 7.2 mg dose, 26.9% of patients met that threshold and went on to lose 27.7% of body weight at week 72. On 2.4 mg, 20.9% qualified as early responders, losing 24.8% at week 72. Non-early responders on the 7.2 mg dose lost 15.4% on average; non-early responders on 2.4 mg lost 13.2%.

🧠 BPS Take: As a product-positioning tactic, this is a sharp move by Novo. The headline number here is 28% weight loss and fast-onset (15% loss) in roughly a quarter of the patients on high-dose semaglutide. Drawing attention to that high-end number compares favorably to tirzepatide, who at the same conference showed SURMOUNT-MAINTAIN data proving that tirzepatide (ZEPBOUND) at max dose sustains 22.4% weight loss through 112 weeks, and published ATTAIN-MAINTAIN data showing patients can switch from injectable ZEPBOUND to oral FOUNDAYO and keep most of the weight off. Lilly’s is trying to position FOUNDAYO as the long-term weight maintenance option, while Novo is trying to highlight the “rapid weight loss” message, while also trying to subtly strike a favorable efficacy comparison to the average ZEPBOUND patient.

But here is where this may backfire for Novo over the long run. By publishing an early-responder analysis, Novo is implicitly acknowledging that GLP-1 response is not uniform. About 27% of patients are early responders on the high dose. That means roughly 73% are not. Novo is essentially segmenting its own market. Right now, that segmentation works in their favor because 27.7% is a great headline. But what happens when the next wave of competitors enters the obesity space with non-GLP-1 mechanisms? Those companies don't need to beat semaglutide in the full population. They just need to target the 73% of patients who are NOT early responders on semaglutide and offer them something better than 15%.

This is especially relevant given the emerging pharmacogenomics data. A major study published in Nature in April 2026 (23andMe, n=27,885 GLP-1 users) identified a missense variant in the GLP1R gene (rs10305420, Pro7Leu) that significantly predicts weight loss response to semaglutide and tirzepatide. The T allele carriers lost meaningfully more weight (additional ~0.76 kg per allele). They also found that response varies significantly by sex (women respond better, 12.2% vs. 10.0% BMI loss in men), ancestry (European ancestry most responsive), and T2D status (patients with diabetes lose ~2.87 percentage points less). Across all non-genetic factors combined, only about 21% of variance in weight loss was explained. Adding genetics bumped it to 25%. We might be moving moving toward a world where “who responds to GLP-1s” is a genetically answerable question.

And that’s the strategic risk for Novo and Lilly alike. Once you can genotype/phenotype for GLP-1 response, the obesity market stops being a one-size-fits-all blockbuster story and starts looking more like precision oncology, where companion diagnostics and patient selection define clinical and commercial outcomes. The non-GLP-1 pipeline is projected to hit $15.5 billion by 2031 (up from ~$310 million in 2026, per GlobalData). Those later entrants would love nothing more than a companion diagnostic or patient segmentation strategy that identifies the patients who won’t respond well to semaglutide or tirzepatide and routes them toward alternative mechanisms instead.

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When the outside world meets biopharma

FDA Commissioner Makary Resigns, Then the Entire Leadership Layer Falls Apart in 72 Hours

📅 May 12-14, 2026 | 🏢 FDA / Policy | 💊 N/A | 🏷 Regulatory Leadership + Industry Response

Marty Makary resigned as FDA Commissioner on May 12, just 13 months into his tenure and on the eve of his Senate Appropriations testimony on the FY2027 FDA budget. The exit was reportedly made under White House pressure after Trump signed off on a plan to oust him, driven in part by Makary’s refusal to approve flavored vapes. Kyle Diamantas, the FDA’s Deputy Commissioner for Food and a JD by training with no medical background, was named acting commissioner. RFK Jr. posted on X that the search for a new commissioner “is already underway.”

But Makary’s exit was just the start. By Friday night, the FDA’s leadership had been gutted across all three critical positions:

Tracy Beth Høeg, acting director of the Center for Drug Evaluation and Research (CDER), was fired on May 15 after she refused to sign a resignation letter.

Høeg was the fifth CDER leader in a single year, following the departures of George Tidmarsh, Richard Pazdur, and others. Michael Davis, CDER’s deputy director, is now acting director.

Katherine Szarama, who had been acting director of the Center for Biologics Evaluation and Research (CBER) for all of 10 days after replacing Vinay Prasad (who himself departed for the second time in April), is also out. Karim Mikhail, former CEO of Amarin who joined FDA last year, is now acting CBER director.

Jim Traficant, FDA chief of staff since last March, was also ousted on Friday.

To summarize the state of affairs: as of this weekend, the FDA has no permanent commissioner, no permanent CDER director, no permanent CBER director, and no chief of staff. All top positions are filled by acting officials operating under a 210-day federal authority limit.

The downstream effects are already visible. Reuters spoke to seven biotech executives, investors, and consultants this week who confirmed that mass FDA layoffs, the revolving door at the commissioner level, and general Trump-era restructuring are pushing smaller biotechs to file Phase 1 INDs in the EU and Australia first. Peter Kolchinsky at RA Capital ($9B AUM) said: “We know that across our companies, the discussions include whether to go ex-U.S. because of recent FDA uncertainty.” One biotech CEO told Reuters their company plans to seek EMA approval to run early-stage oncology trials in three European countries, at roughly $1M in additional filing costs, saying: “The irony of this is it goes against the grain of ‘America First’, because we are offshoring away from the U.S. over to Europe.” Another U.S. biotech opted to run two early-stage trials in Australia this month rather than the U.S. A third said at least two members of their eight-person FDA review team have left, threatening data review timelines.

🧠 BPS Take: Makary’s tenure was a mostly negative bag in my view. He directionally had it right on some things like: utilization of AI, CRL transparency, and speeding up review times, but none of those were ever applied consistently enough to result in more benefit than harm to the sector. Moreover, he really hired some problematic people, who he as a leader did not do a good job reigning in and did an equally job managing-up with his superiors like RFK and Trump.

What is alarming is what happened in the 72 hours after he left. The acting CDER head was fired. The acting CBER head (who had the job for 10 days) is gone. The chief of staff is gone. Apparently the Chief AI officer (which to be honest I didn’t know was a thing at the FDA) is also out.

The person now running the entire FDA is a food lawyer whose prior claim to fame was defending Abbott in an infant formula lawsuit (Abbott lost, paid $495M) and who is a close friend of Donald Trump Jr. A food lawyer running a drug-heavy agency is not a confidence-inspiring signal for anyone waiting on a PDUFA date.

This is just the cherry on top of all the turmoil, capriciousness, and inconsistency this FDA has demonstrated since Trump came into office for a second time. All of that compounds. The agency is operationally diminished at the absolute wrong time, as we fall further behind China in innovating new drugs and testing them in clinical trials. The biotech offshore migration story is the direct, logical consequence. When your fastest path to a Phase 1 readout runs through Melbourne or Amsterdam rather than Rockville, you file there.

I am not confident anyone of meaningful stature, competence, and leadership will take any of these roles. Several big name figures in the Biotech community are petitioning for Rick Pazdur to return. While he would be an experienced and perhaps stabilizing pick, why would anyone want this job if you have to compromise your morals to defend RFK’s ludicrous takes on health and wellness and push through the agenda of any random person who has the president’s ear?

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

BMS Pays $600M Upfront for $15.2B Hengrui Mega-Pact While $GSK Hands China HBV Launch to Sino Biopharmaceutical

📅 May 11-12, 2026 | 🏢 Bristol Myers Squibb ($BMY) + Hengrui Pharma ($1276.HK) + GSK ($GSK) + Sino Biopharm ($1177.HK) | 💊 13 early-stage oncology/hematology/immunology assets + bepirovirsen | 🏷 Strategic Licensing / Co-Development Alliance + China Commercialization Partnership

Bristol Myers Squibb ($BMY) and Hengrui Pharma ($1276.HK) announced a sweeping bilateral pact on May 12 worth up to $15.2 billion in total milestones. BMS pays $600 million upfront, plus $175 million on each of the first two anniversaries, to secure ex-China rights to four Hengrui oncology and hematology assets and joint discovery rights on five additional programs. Hengrui receives Greater China rights (mainland China, Hong Kong, Macau) to four BMS immunology assets and will lead early human development in that region. The transaction is expected to close in Q3 2026.

BMS CFO David Elkins had publicly flagged at a Citi event that China’s early-stage development speed is a competitive advantage, citing McKinsey data showing Chinese sponsors run proof-of-concept trials 50 to 70 percent faster than Western peers. This deal arrives roughly a year after Hengrui’s $12 billion licensing agreement with GSK, cementing Hengrui’s status as the most sought-after Chinese R&D partner in the industry right now.

One day earlier, on May 11, GSK ($GSK) moved in a different direction with China exposure by announcing an exclusive collaboration with SBP Group, the hepatology-focused unit of Sino Biopharmaceutical ($1177.HK), to support the China launch of bepirovirsen, a potential first-in-class antisense oligonucleotide for chronic hepatitis B. Under the 5.5-year supply arrangement, CTTQ purchases the drug from GSK while GSK retains all revenue recognition.

🧠 BPS Take: Two deals, two flavors of the same strategic logic: Western pharma cannot ignore China’s patient populations or its R&D throughput, regardless of geopolitical headwinds. I find the BMS/Hengrui structure particularly interesting because it is almost a trade of sorts. BMS buys into part of a Chinese pipeline, but it is also licensing its own immunology assets back into China through a local partner who will run early development there. That is a mature, cost-conscious way to keep China exposure without building out your own local clinical infrastructure. The $600 million upfront is real money on undisclosed early-stage assets, which tells you how seriously BMS is treating its post-REVLIMID pipeline rebuild. I am curious to see what targets and modalities end up coming out of Hengrui for this deal.

The GSK/Sino bepirovirsen deal is structurally simpler but strategically smart. GSK is not giving up economics; it is essentially buying a distribution army in a foreign market. If bepirovirsen clears China’s NMPA and delivers even modest functional cure rates, that 5.5-year supply pact becomes very valuable very fast.

I’ll also be watching whether these deals attract scrutiny under the BIOSECURE Act or successor legislation. Also watching how Hengrui’s stock responds over the next month, because if this gets blocked or renegotiated, the ripple effects for the entire wave of China in-licensing deals will be significant.

Isomorphic Labs Pulls In $2.1B Series B, Becoming the Largest Single Bet on AI Drug Discovery

📅 May 12, 2026 | 🏢 Isomorphic Labs (subsidiary of Alphabet, $GOOGL) | 💊 AlphaFold-derived AI drug design platform | 🏷 Mega Series B Financing

Isomorphic Labs, the DeepMind spinout founded by Demis Hassabis, closed a $2.1 billion Series B led by Thrive Capital, with participation from new investors MGX (the Abu Dhabi state-linked technology fund), Temasek, and CapitalG, alongside existing backers Alphabet ($GOOGL) and GV. BioSpace reports this is the second-largest biotech financing round ever recorded. Proceeds will fund expansion of the company’s generative drug-design models built on top of AlphaFold’s structural biology foundation.

Isomorphic has been operating largely in stealth on its own internal pipeline while licensing its platform capabilities to partners including Eli Lilly and Novartis. The fresh capital is expected to accelerate moving those computational designs into wet-lab validation and, eventually, clinical programs. Forbes describes the round as “the biggest bet yet on AI drug discovery,” framing the fundraise against a broader investor thesis that generative AI will compress preclinical timelines by years, not months.

🧠 BPS Take: $2.1 billion for a company with no approved drug and no disclosed Phase 1 data is a remarkable statement of faith in a platform. The investors backing Isomorphic Labs are overwhelmingly tech-first investors and mega-funds, rather than biotech VCs. While the headlines are biotech/drug development focused, Isomorphic is really being priced like a Tech/AI company and not a drug developer. Isomorphic is building upon AlphaFold’s protein prediction capabilities to also modeling potential druggable sites on the target and using AI to create several “keys” that fit into those binding pockets. Ultimately, these still need to tested in animals and then humans, but their platform can conceivably cut out a lot of the fat of generating drug leads in a program. The proof will be in the pudding, and IsoMorphic, with Google’s backing is partnered with multiple Big Pharmas on drug discovery collaborations. Let’s keep an eye on timelines to IND here and how quickly IsoMorphic is able to progress their own programs. As we’ve seen with other AI drug discovery companies, like Recursion, these tech-first companies can raise huge rounds, sign multiple big collabs, and get a several year grace period where they crank out several “cool” drug candidates before the pressure of actually getting drugs to work in the clinic sets in.

Create Medicines Raises $122M Series B to Bring RNA-Based In Vivo CAR-T Into the Clinic

📅 May 14, 2026 | 🏢 Create Medicines (private) | 💊 In vivo CAR-T platform (autoimmune + oncology) | 🏷 Series B Financing

Create Medicines, a Massachusetts-based biotech developing RNA-based in vivo CAR-T therapies, announced a $122 million Series B led by Newpath Partners, with ARCH Venture Partners and Hatteras Venture Partners joining the round. The company’s platform is designed to engineer CAR-T cells directly inside the patient’s body using RNA delivery, bypassing the costly and logistically complex ex vivo manufacturing process that currently limits conventional CAR-T to a small number of academic medical centers.

The round positions Create in the same rapidly consolidating in vivo CAR-T subspace as Lilly’s $7 billion acquisition of Kelonia earlier this year and the AbbVie ($ABBV) partnership with Capstan Therapeutics. STAT News notes that Create’s autoimmune disease focus mirrors where conventional ex vivo CAR-T has already shown dramatic early results, with the in vivo approach offering the potential to reach far more patients if manufacturing hurdles can be eliminated. Proceeds will fund IND-enabling studies and the company’s first clinical programs.

🧠 BPS Take: The in vivo CAR-T space is moving faster than almost any other subfield in cell and gene therapy right now. Create’s $122 million round is well-sized as it is one of the few in vivo companies with clinical data (in solid tumors to boot). From their corporate presentation, it appears they have a broad set of cell and antigen targeting technologies across oncology and autoimmune disease. Given the high density of players in this space, speaking to and proving differentiation in your vector’s targeting capabilities vs. competitors will be important, and Create does a good job explaining where they may be better than their peers. In solid tumors, they’ve already shown one partial response with a TROP2 CAR-myeloid cell program. It appears their approach in solid tumors is also guided at in vivo delivery into multiple cell types at once (NKs, Myeloids, T-cells, etc.) which is somewhat unique to them. More robust clinical data across all these programs will be the true test, but it is good to see companies speak to aggressively speak to differentiation against competitors early on. Create is definitely one to follow as we head into conference season, and given the penchant for Big Pharmas to acquire in vivo Cell Therapy companies early-on in their company life cycle, perhapsLet’s do a remixed version of this image. Make it “Week of May 11.” Also, only include logos for FDA, Novo Nordisk, and Bristol-Myers Squibb. they won’t be around for long.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

Of all the types of cancers, blood cancers have perhaps seen the most meaningful therapeutic advances. People often joke that blood cancers are the “the good cancers”, since a large chunk of them are quite curable or manageable long-term. Chronic Myeloid Leukemia (CML) patients have normal life expectancy because of the advent of tyrosine kinase inhibitors like GLEEVEC. Chronic Lymphocytic Leukemia (CLL) is well managed with BTK inhibitors. Acute Lymphoblastic Leukemia (ALL) and pretty much all types of B-cell lymphomas are curable with chemo-immunotherapy or CD19-based CAR-T therapy. Multiple Myeloma has steadily seen increases in overall survival with discovery of novel targets, new modalities (CAR-T and T-cell engagers) and multi-drug regimens, so much so that many leading key opinion leaders feel myeloma is entering its chronic disease era.

It has truly been one of the most optimistic areas of cancer research. I think that is why everyone really loves going to the annual American Society of Hematology (ASH) meeting every year. You’ll regularly see new data from novel MOAs that have response rates in the 90’s and complete response rates in the 70s and 80s.

That certainly isn’t the case for every hematologic malignancy. Drug-knowers will realize I omitted some pretty meaningful diseases from that list, notably acute myeloid leukemia (AML) and myelofibrosis (MF), which the rest of this post is about. Not every cancer your blood can get has yet to benefit from the major advancements our field has been able to materialize in advanced therapeutics.

But it has to be coming soon right? It must just be market forces that haven’t trickled their way down to the smaller blood cancers yet. Lymphomas and myelomas are sizable competitive markets, but those same step-change innovations we brought forth should certainly find their footing in MF, right? After all, Lilly (of all companies) just bought a company developing an MF drug for up to $2.3B

The Prolonged JAKAFI Era

Early on in my BioPharma career, I spent a great amount of my time focused on blood cancers, of which myelofibrosis (MF) was one of them. Back when I was covering this space, there was only one game in town - JAKAFI. JAKAFI is Incyte and Novartis’ JAK inhibitor which truly revolutionized treatment for MF. Before its arrival in 2011, treatment was largely reactive and palliative, relying on non-specific agents like hydroxyurea that often failed to address the core symptoms of the disease. It provided the first consistent way to significantly reduce massive splenomegaly (enlarged spleen) and debilitating constitutional symptoms like night sweats, bone pain, and extreme fatigue, which drastically improved patients' quality of life. But more importantly, it was the first to show an overall survival benefit.

As is the case with so many markets in BioPharma, a new idea doesn’t often get pursued in a vacuum. Other players (Gilead included) looked to advance slightly more refined version of JAK1/2 inhibitors to improve on JAKAFI’s profile.

However, it took almost 8 years for new JAK inhibitor to make it to market. While JAKAFI displayed great symptom resolution (TSS) and spleen reduction (SVR), it tended to cause very high rates of anemia, which would often require patients to get blood transfusions. Treatment with next-gen JAK inhibitors from competitors shifted towards moderating SVR to spare red blood cells and reduce the blood transfusion requirements. Now there are four JAK inhibitors approved (all the ones you see in the table above) all with their particular niche in the market place.

Despite all this competition, JAKAFI still reigns supreme, but is facing a growing threat from OJJAARA, which has quickly become the go-to treatment for patients with anemia. This is a classic case of first-mover advantage paying off. JAKAFI has had significantly more time on market than its competitors, more physician experience with its product, the most robust survival data, and the benefit of still being the preferred medicine in treatment guidelines, and also the preferred treatment on formularies. But trouble may be on the horizon. Generic ruxolitinib entry is now estimated as early as December 2028, and Incyte has already faced patent litigation from generic challengers. The extended-release formulation approval is one defensive move, but whether it drives meaningful patient switching before generics arrive is an open question.

All that being said, when I put together the MF landscape for this post, I was surprised to see that the entire approved treatment portfolio is still just varieties of JAK inhibitors.

Too soon to subscribe? I have an idea.

The Late-Stage MF Graveyard

However, it’s not like other strategies weren’t tried. MF’s history has some recent failures in its memory:

• PI3K-delta inhibitors: This class was studied in combination with JAKAFI to enhance response. JAK inhibitors are great at reducing symptoms and shrinking the spleen, but do not slow or reverse marrow fibrosis or offer a path to cure. Incyte had its own program in this vein (parsaclisib), but it’s pivotal study was stopped early due to the added benefit over JAKAFI alone being too small to justify the added risk of thrombocytopenia.

• Luspatercept (activin receptor ligand trap): Also known as REBLOZYL, this drug was aimed at reducing transfusion dependence. Unlike in MDS where it has proved to be successful, luspatercept failed to a show an improvement in this metric in MF patients.

• Apoptosis pathways: Along the same vein as PI3K-delta, companies looked to target the p53 apoptotic pathway via MDM2 and BCL-2 inhibitors to add to JAK1/2 inhibition efficacy. AbbVie pushed all the wya into two Phase 3 studies with navitoclax (BCL-2 inh) but ultimately scrapped development in MF after one of its studies was unable to show a benefit in TSS, despite a significant benefit in SVR. Kartos and Novartis each advanced their own respective MDM2 inhibitors. Novartis ended up deprioritizing it’s asset, while Kartos’ navtemadlin continues on in a P3 study in 1L MF after mixed results in a P3 study in 2L+ MF.

• Other approaches: A couple more that have had disappointing results: Hedgehog inhibitors, most notably Pfizer’s glasdegib, was terminated due to lack of efficacy and GI toxicity issues. Novartis tried an anti-TIM3 antibody, pursuing an immuno-oncology approach to myelofibrosis, but that was also terminated due to lack of efficacy.

Common theme across these tried-and-failed approaches is toxicity issues in combination with JAKAFI, commonly myelosuppression. The bar for success is unusually high in myelofibrosis as well. JAKAFI was approved showing improvements in total symptom score and spleen volume reduction. Many of the failures in this space have been able to show spleen volume reduction, but have failed to show a significant improvement in symptoms. While the combinatory drugs are helping to kill malignant cells more effectively, they come with additional adverse events canceling out the symptomatic relief patients feel.

More mechanistically, prolonged use of JAKAFI and other JAK inhibitors can downstream lead to mutations that render the baseline JAK backbone ineffective. The JAK problem is hard to avoid, just given how central the JAK-STAT pathway is to the pathology of myelofibrosis. However, thinking has shifted on what the appropriate endpoints for novel therapies in this space should be. The field is moving away from the “spleen-centric” era where SVR and TSS were essentially surrogate measures of efficacy; now the next wave of novel therapies are focused on showing hard outcomes like overall survival, demonstrating bone marrow fibrosis reduction (BMF grading), and reduced burden of mutant clones (Variant Allele Frequency, VAF). This offers some newfound hope to a new set of therapeutic strategies being pursued in early/mid-stage clinical development.

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So Where is the Field Headed?

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

This week, Cytokinetics hit it big non-obstructive hypertrophic cardiomyopathy setting up strategic crossroads, FDA instability crops up once again with Marty Makary likely to be fired by Trump, and Roche takes a major step in AI.

All that and more below. Let’s get into it!

But before that….Happy Mother’s Day to all moms, grandmothers, and mother figures reading this! This day always brings my mind back to women’s health. Both how far we’ve come and how far we still have to go.

Over the last five years we’ve delivered several new treatments in women’s health (outside of oncology): Zurzuvae (2023), the first oral postpartum-depression treatment; Veozah (2023), the first non-hormonal hot-flash therapy; and Orilissa and Myfembree, the first new oral endometriosis drugs in over a decade. Women’s health VC funding hit a record $2.6 billion in 2024, up 50% year-over-year.

Yet despite these new advances, it is so clear we still have a long way to go. Endometriosis affects ~190 million women, takes nearly seven years to diagnose, and has no disease-modifying therapy. PCOS, the most common endocrine disorder in reproductive-age women, has zero FDA-approved treatments. There are several studies ongoing studying GLP-1s in this space, with hopefully positive data forthcoming. Uterine fibroids affect up to 80% of women by age 50 and up to 90% of Black women, yet for decades the default “treatment” was hysterectomy. Preeclampsia causes over 70,000 maternal and 500,000 fetal deaths annually, with the only treatment being delivery. Black women in the U.S. die from pregnancy-related causes at 3.5× the rate of white women. Two-thirds of Alzheimer’s patients are women. 80% of autoimmune-disease patients are women. Yet only ~6% of private healthcare capital targets women’s conditions.

We've made progress, but we're nowhere near where we need to be. Women's health is human health. Our industry has the the tools, obligation, and and alignment with financial interests to make even more progress over the next five years.

Now onto an interesting week in BioPharma.

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📡 PRESS RELEASE DECODER

What the press releases actually mean

Cytokinetics’ Aficamten Hits Both Endpoints in nHCM — First Positive Phase 3 in a Population With Zero Approved Therapies

📅 May 5 | 🏢 Cytokinetics ( ) | 💊 Aficamten (MYQORZO) | 🏷 Phase 3 Topline Data

Cytokinetics reported positive topline results from ACACIA-HCM, the pivotal Phase 3 trial of aficamten in symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM). The trial randomized 516 patients 1:1 and met both dual primary endpoints at Week 36: KCCQ-CSS improved by 3.0 points over placebo (95% CI 0.5–5.5, p=0.021), and peak VO2 improved by 0.67 mL/kg/min over placebo (95% CI 0.22–1.1, p=0.003). All key secondary endpoints also hit with high significance (p<0.001), including NYHA functional class improvement, composite exercise parameters, and NT-proBNP reduction.

Safety was consistent with the known cardiac myosin inhibitor profile. LVEF fell below 50% in 10% of aficamten patients versus 1% on placebo. Two patients on aficamten had serious adverse events of heart failure associated with low LVEF. Dose interruptions for LVEF <40% occurred in 3% of aficamten-treated patients. Completion rates were comparable between arms (88.4% vs 90.3%).

This is aficamten’s second Phase 3 win — the first was SEQUOIA-HCM in obstructive HCM, which supported the FDA approval of aficamten as MYQORZO for symptomatic oHCM (already approved in the U.S., EU, and China). Cytokinetics has signaled it will file a second sNDA for the nHCM indication based on ACACIA-HCM data. Full results are expected at an upcoming medical congress.

🧠 BPS Take: This is a genuinely important clinical result. The nHCM population, which represents roughly half the HCM population, has had no approved disease-modifying therapy. Cardiologists have had nothing to offer except symptom management and the assumption that without obstruction, the disease was pharmacologically harder to treat. ACACIA-HCM changes that completely.

Strategically, this puts Cytokinetics in a position BMS cannot match. If the nHCM sNDA converts to approval, aficamten becomes the only cardiac myosin inhibitor labeled for both obstructive and non-obstructive HCM, giving CYTK commercial opportunity across the full spectrum of HCM. Remember, BMS’ Camzyos (mavacamten) failed in the P3 ODYSSEY-HCM study, leaving this opening for CYTK to be first-to-market in nHCM. BMS is working on a new study to tackle nHCM with CAMZYOS, but they will undoubtedly be later to market, after spending $13B to acquire mavcamten from MyoKardia in 2020.

The question I keep coming back to: does a second Phase 3 win in the same disease space accelerate acquisition interest, or does Cytokinetics now have enough standalone value to stay independent? CYTK was a name I called out on my buyout list earlier in the year. They are sitting at just under $10B in market with a product that may get low single-digit billions in revenue. The BMS precedent of $13B may be where some acquirers anchor too, but CYTK may be able to garner more given their competitive edge. CYTK could make sense for a strong CV player like Novartis or AstraZeneca. Watch the BD chatter closely over the coming months.

FDA Agrees to Reconsider Ebvallo CRL — Pierre Fabre Gets a Path Forward After a Rejection That Didn’t Add Up

📅 May 7 | 🏢 Pierre Fabre / Atara Biotherapeutics ( ) | 💊 Ebvallo (tabelecleucel) | 🏷 FDA Type A Meeting / Regulatory Update

Pierre Fabre announced that the FDA has completed a Type A meeting on the Complete Response Letter (CRL) issued in January 2026 for tabelecleucel, an allogeneic, off-the-shelf EBV-specific T-cell immunotherapy for EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). The meeting outcome provides a resubmission path — Pierre Fabre described the discussion as reaching an accord on the BLA path forward. Type A meetings are reserved for urgent matters, including disputes over CRL decisions, and the FDA’s willingness to engage at this level signals meaningful internal reconsideration.

Tabelecleucel targets an ultra-rare, frequently fatal malignancy in immunocompromised post-transplant patients who have failed rituximab. Unlike autologous cell therapies, it doesn’t require patient-specific manufacturing — a critical advantage in a population often too ill to wait for custom products. The original CRL was widely described as inconsistent with prior FDA guidance the agency had provided to the sponsor during development.

🧠 BPS Take: The FDA walking back a CRL like this is not normal, and continues along a pattern of FDA capriciousness we have seen under this administration. Type A meetings exist for urgent disputes, but the agency providing a clear resubmission path on a rejection that both the company and external observers described as contradicting prior guidance is genuinely odd.

This story matters on two levels. First, tabelecleucel is a an allogeneic, off-the-shelf EBV-specific T-cells for critically ill transplant patients with almost no alternatives. The original CRL was always hard to reconcile with the clinical and regulatory logic of the program.

Second, and more troubling, the same week Sanofi pulls Tzield from a priority review program citing political appointee interference, we have the FDA providing a resubmission path on a rejection that didn’t track with its own prior guidance. Pair that with other controversial decisions we’ve seen this year (e.g. Replimune, UniQure, Sarepta, etc.) and you have one of the most important regulatory agencies on shaky ground. More on this in Connecting the Dots.

Incyte Gets Jakafi XR Approved — Lifecycle Management Play With a Tight Window Before the Patent Cliff

📅 May 1 | 🏢 Incyte ( ) | 💊 Jakafi XR (ruxolitinib extended-release) | 🏷 FDA Approval

The FDA approved Jakafi XR, a once-daily extended-release formulation of ruxolitinib, across all three approved indications: myelofibrosis (MF), polycythemia vera (PV), and graft-versus-host disease (GVHD). The existing twice-daily Jakafi remains on the market. The XR formulation is designed to maintain therapeutic exposure over a 24-hour dosing interval, with the rationale that once-daily dosing improves adherence in a chronic disease population.

Jakafi is Incyte’s largest commercial asset. In Q1 2026, Jakafi generated $758 million in U.S. net sales — annualizing to roughly $3 billion. The drug’s core patents are expected to expire around 2027-2028, creating significant near-term generic exposure. The MF treatment landscape has grown more competitive since Jakafi’s original approval: pacritinib, fedratinib, and momelotinib are all FDA-approved alternatives with differentiated profiles in specific subpopulations.

🧠 BPS Take: This is one of the purest forms of lifecycle management. I don’t say that dismissively. This is what brands close to the end of their exclusivity do. Spin up an extended release formulation or a new route of administration. That new offering has its own patent life that can extend beyond the LOE of the original formulation. Incyte’s bread and butter is Jakafi and its staring at an estimated 2028 patent cliff on a ~$5B product (including Novartis’ share of revenues).

Once-daily dosing is a tangible convenience benefit compared to immediate release (twice-daily) Jakafi, but brings it to parity with most of the other JAK inhibitors in the myelofibrosis and polycythemia vera space. The push here will come from the Jakafi commercial teams aiming to influence patient and docs to switch to the XR formulation over the two year window prior to Jakafi IR coming off patent. Incyte tried to give themselves more runway for this, but ran into regulatory issues during their first attempt at an XR formulation back in 2023. Payers may not automatically cover Jakafi XR over generic ruxolitinib once generics hit the market, unless they are getting a big discount on the back end.

I think the bigger question for me is why is everything in MF still a JAK inhibitor? Aside from the other JAK inhibitors that have been approved in this space, this XR formulation is the last major innovation the MF landscape has seen. I am digging into this curiosity in a forthcoming post for paid subscribers, so stay tuned.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

The FDA is Coming Apart — Makary Firing, Flavored Vapes, RFK’s SSRI Push, and What It Means for Drug Development

📅 May 4–8, 2026 | 🏢 POLICY/MACRO | 🏷 FDA Credibility Crisis

Monday, May 4: HHS Secretary Robert F. Kennedy Jr. announces the “MAHA Action Plan” at a Mental Health and Overmedicalization Summit, announcing federal initiatives to reduce SSRI antidepressant prescribing. The plan includes new Medicare/Medicaid reimbursement for clinicians who help patients taper off psychiatric medications, prescribing trend transparency, and provider training. Kennedy’s statement: “Psychiatric medications have a role in care, but we will no longer treat them as the default.” Kennedy has previously, without evidence, linked SSRIs to mass shootings and claimed withdrawal symptoms are worse than heroin.

Tuesday, May 5: The Wall Street Journal reports Trump directly pressured FDA Commissioner Makary to approve flavored e-cigarettes. Makary had been blocking authorization since a February memo indicated he needed more time to evaluate the science. The same day, Sanofi requests removal of Tzield from the FDA’s Commissioner’s National Priority Voucher (CNPV) program after CDER head Dr. Tracy Beth Høeg became directly involved in the review.

Wednesday, May 6: The FDA announces its first-ever authorization of fruit-flavored e-cigarettes — four products from a company called Glas with Bluetooth age-verification technology. The timing, coming immediately after Trump’s pressure became public, is impossible to ignore. Public health groups and a bipartisan group of senators (Durbin and Collins) criticize the decision.

Thursday, May 7: New York Post runs “Knives out for FDA head Marty Makary.” NBC reports Trump is considering firing him. The frustrations are multiple and overlapping: slow-walking flavored vape approvals, failure to release a promised mifepristone safety review before midterms (Bloomberg reported in December that Makary told officials to delay it), the UniQure Huntington’s gene therapy rejection that led to Vinay Prasad’s second ouster, and the Moderna mRNA flu vaccine application refusal that was reversed days later.

Friday, May 8: Two stories break simultaneously. CNN reports Trump has “signed off” on a plan to oust Makary, according to a senior administration official, though no formal dismissal has occurred and Trump told reporters “I’ve been reading about it, but I know nothing about it.” Separately, Reuters reports exclusively that Kennedy’s HHS officials explored whether they could ban specific SSRIs — including Zoloft, Prozac, and Lexapro — as Kennedy prepared his MAHA plan. HHS denies the report. Regulatory experts are uniform: the FDA cannot unilaterally ban approved medications without new safety evidence. The American Psychiatric Association considers SSRIs a first-line, evidence-based treatment for depression and “strongly objects to framing the nation’s mental health crisis as primarily a problem of ‘overmedicalization.’”

🧠 BPS Take: If you've been a regular BPS reader you won't be surprised by this volatile behavior from the FDA, but this week felt like it reached a new level. Three threads connect.

First, Makary blocked flavored vapes in February based on a scientific review he said needed more time, Trump pressured him directly, and the FDA reversed course within days of that pressure becoming public. Whether or not the flavored vape authorization is scientifically defensible, it sure feels like a science-based decision was reversed under direct presidential pressure, and that is not how the FDA is supposed to work. Yet another example of why we should consider making it a more independent body, like the Fed.

Second, Kennedy's HHS exploring an actual ban on specific approved SSRIs threatens to set a dangerous precedent if it happens. These are drugs backed by decades of clinical evidence and considered first-line treatment by every major psychiatric organization. There is an argument to be made for combatting overprescription, but an outright ban would likely do more harm than good. The FDA doesn't have the legal authority to unilaterally ban approved drugs without new safety evidence, and this would require formal safety review processes that take months or years, but the signal this exploration sends to the industry, that approved drugs could be targets of political campaigns, is profoundly destabilizing.

Third, CNN reports Trump has signed off on ousting Makary but hasn't formally acted, in part because there's no replacement lined up. There are already so many holes in the FDA after so much staff turnover, and if Makary goes, that's another major destabilizer to an already chaotic agency. It's not like we've seen a deep bench of competent operators in this administration either, and I am not too confident that whoever takes over will exceed an already low bar.

The through-line across all three is an FDA that has operated inconsistently in the face of direct political pressure from higher-ups, and the unpredictability at the review level is emblematic of that. When Sanofi exits a priority review program because a political appointee intervened in a way the company couldn't predict, when the Ebvallo CRL contradicts prior guidance, when Moderna's flu vaccine application gets rejected then un-rejected within days, and when the Commissioner himself may be fired for not approving consumer products fast enough, the review process itself stops being rule-governed.

BioNTech Cuts 1,860 Jobs and Closes Four Manufacturing Sites

📅 May 5 | 🏢 BioNTech ( ) | 🏷 Restructuring / Workforce Reduction

BioNTech announced the elimination of approximately 1,860 manufacturing positions — roughly 25% of its global workforce — and the closure of four facilities: Idar-Oberstein, Marburg, and Tübingen in Germany (closing by end of 2027) and a Singapore site (closing during 2026). All four were scaled up during the pandemic for mRNA vaccine production. BioNTech’s COVID vaccine revenues peaked at approximately €19 billion in 2021. The company is funding an oncology pipeline pivot on depleting reserves, with lead mRNA cancer vaccine programs BNT111 (melanoma) and BNT116 (lung cancer) in Phase 2 — neither generating revenue.

🧠 BPS Take: BioNTech rose to prominence on the back of its COVID-19 vaccine business. As has been the case for other COVID-19 drug makers in that space, sales have been on a steady fall. Declining demand warrants pairing back capital expenditures for that business segment.

BioNTech was always an Oncology company at its core. Modality agnostic and Oncology focused. They’ve built an impressive pipeline in that therapeutic area, spanning bispecific antibodies, mRNA vaccines, ADCs, and other modalities. COVID-19 always felt like they were in the right place at the right time. While layoffs and site closure are never smooth, this is probably the right long-term moved (despite the short-term pain) to reallocate resources towards its oncology business.

What I am curious about is who will take over the helm of this company and guide it during this new chapter, while all this restructuring is in the works? The founders are stepping out to run a new spinout and it feels like this should be quite an attractive job opportunity for an outsider. I’m sure the board has no shortage of interested candidates. BioNTech is set up well to be a pure play oncology growth story. It has multiple late-stage studies across a diversified set of assets with rather large market opportunities and is well capitalized to invest in its own commercial future and invest in novel early-stage bets.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Bayer Acquires Perfuse Therapeutics for Up to $2.45B — First Drug Deal in Years Targets the Glaucoma Adherence Problem

📅 May 6 | 🏢 Bayer ($BAYN.DE) / Perfuse Therapeutics (Private) | 💊 PER-001 (intravitreal implant) | 🏷 M&A — Acquisition

Bayer will acquire Perfuse for $300 million upfront and up to $2.15B in milestones. The deal’s centerpiece is PER-001, an intravitreal implant currently in Phase 2 for glaucoma and diabetic retinopathy. The implant blocks a protein that constricts blood vessels and contributes to ocular damage — a mechanistically distinct approach from existing treatments. In glaucoma, it’s being studied as a way to improve vision; in diabetic retinopathy, it targets retinal blood flow restriction. Perfuse reported positive Phase 2 data in both indications last year. This is Bayer’s first major drug company acquisition since 2021.

🧠 BPS Take: Bayer has been in need of something to revitalize the prospects of its drug business. They’ve been in restructuring mode under CEO Bill Anderson since his arrival, the pharma pipeline has been visibly thin, and Eylea’s biosimilar exposure was always going to require a pipeline answer. The deal structure is fairly sensible for Bayer. This sort of backloaded deal probably works out better for them given how much debt they are saddled with and litigation payment obligations. This doesn’t solve all their problems, but is a step in the right direction. Hopefully one day in the future they will take their medicine and break up their disparate businesses into separate entities.

Roche Acquires PathAI for Up to $1.05B — The Most Strategically Coherent AI-Pharma Deal This Year

📅 May 7 | 🏢 Roche ( $ROG.SW ) / PathAI (Private) | 💊 AI digital pathology platform | 🏷 M&A — Acquisition

Roche will pay $750 million upfront with up to $300 million in milestones for PathAI, an AI-powered digital pathology company. PathAI’s platform applies machine learning to analyze pathology slides for cancer diagnosis, biomarker identification, and companion diagnostic development. PathAI had raised approximately $255 million in venture funding. The acquisition positions Roche to integrate AI-driven pathology directly into its $16 billion diagnostics business (Roche Diagnostics, Ventana).

🧠 BPS Take: This is one of the most strategically coherent AI-pharma deals I’ve seen. Roche can integrate PathAI into a $16B diagnostics business that already sits at the intersection of oncology, companion diagnostics, and drug development. They are getting a data flywheel: every pathology slide processed through PathAI’s algorithm improves the model, which improves diagnostic accuracy, which improves clinical trial patient selection, which improves drug approval rates. Overtime this starts to look like a competitive moat that gets harder to replicate with every slide processed.

In oncology you sort of have two paths to success. Go broad or go narrow. Go broad is a lot harder to do, requires some luck, but in the end you can end up with a drug like Keytruda that is approved in nearly every solid tumor, or even Rituxan, which blanketed all of B-cell malignancies in its heyday. Narrow requires precision. This is your classic companion diagnostic or biomarker driven treatment strategy. Find the sub-segment that your drug really responds to and carve out a strategically advantageous position in that sub-segment. Revolution Medicines is doing this to great effect right now in mKRASG12 pancreatic cancer, but we have so many examples of building strong businesses with this strategy (ALK, EGFR, HER2, BRCA, etc.), and this PathAI deal seems like it will better equip Roche to take advantage of that.

GSK Licenses ALK7-Targeting siRNA from China’s SiranBio in Up to $1B Cardiometabolic Deal

📅 May 6 | 🏢 GSK ( ) / SiranBio (Private, China) | 💊 SA030 (siRNA targeting ALK7) | 🏷 Licensing Agreement

GSK licensed global rights to SA030, an siRNA therapeutic targeting ALK7 (activin receptor-like kinase 7) for visceral fat reduction and cardiometabolic disease, from China-based SiranBio. Deal terms: $55 million upfront, up to $1 billion in milestones. SA030 is in Phase 1 with no public efficacy data. ALK7 inhibition has been shown preclinically to selectively reduce visceral adipose tissue — the metabolically harmful fat depot associated with cardiovascular disease, insulin resistance, and type 2 diabetes.

🧠 BPS Take: GSK’s cardiometabolic strategy is about being complementary to GLP-1s. Unlike their peers rushing to find the me-three/four GLP-1 to bring to market, GSK is telling you that they’re not interested in that. They’d rather be a combinatory partner to a GLP-1 backbone to enhance specific treatment effects. This ALK7 asset aims to more heavily target visceral fat, which a lot of science points to as one of the primary drivers of metabolic dysfunction. GLP-1s already help reduce visceral fat to a good degree, but perhaps adding ALK7 inhibition can further that. Notably there are still patients who don’t respond to GLP-1s or respond sub-optimally, and this sort MOA that works more on the thermogenesis and adipocyte targeting axis could be an effective alternative.

Back next week with more BioPharma strategy takes! Share this with a friend of colleague if you found it helpful.

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week! I had a hard time pairing this one down given all the interesting activity we saw. Many deals, data readouts, and strategic updates left on the cutting room floor.

This week, Sun Pharma dropped $11.75B on Organon in a rare India ➡️ US deal, AstraZeneca had a split ODAC day, and Intellia lands the first in vivo gene editing drug to register a positive Phase 3 readout but no one told the stock price. Meanwhile, the FDA is running fast to make real-time clinical trials standard practice, Lilly continues its deal spree, and IPO markets are looking healthy again.

All that and more below. Let’s get into it!

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For instance, this week I wrote an essay about prediction markets for clinical trial outcomes, comparing them to sports betting markets to learn about their limitations, and discuss why these types of markets are likely to be a net negative for drug makers and patients.

If you’re not ready to commit to being a paid subscriber, but still want to support my work, you can always show your appreciation by buying me drink 😉

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📡 PRESS RELEASE DECODER

What the press releases actually mean

AstraZeneca’s Split ODAC Day — Camizestrant 6-3 Against, Truqap 7-1 In Favor

📅 Date: 2026-04-30 | 🏢 Company: AstraZeneca ( ) | 💊 Drug/Asset: Camizestrant (SERD), Truqap (capivasertib, AKT inhibitor) | 🏷 Event Type: FDA ODAC Votes

AstraZeneca faced two ODAC votes on the same day (the committee’s first meeting in nine months) and walked away with a split decision. In the morning session, ODAC voted 6-3 against the benefit-risk profile of camizestrant, an oral SERD, for HR+/HER2- metastatic breast cancer. In the afternoon, the same committee voted 7-1 (one abstention) in favor of Truqap (capivasertib) plus abiraterone and prednisone for PTEN-deficient metastatic hormone-sensitive prostate cancer.

The camizestrant rejection wasn’t a straightforward efficacy dispute, it was a rejection of AstraZeneca’s entire proposed treatment paradigm. The SERENA-6 trial used circulating tumor DNA (ctDNA) monitoring to detect ESR1 mutations while patients were still responding to first-line therapy (aromatase inhibitor + CDK4/6 inhibitor), then switched them to camizestrant before radiographic disease progression. The trial showed a 56% PFS improvement, median 16.0 months vs. 9.2 months for patients who stayed on the aromatase inhibitor. But OS data were immature with no benefit signal, the control arm didn’t allow crossover to camizestrant, and only 14% of control patients received any oral SERD in subsequent treatment.

The FDA’s core objection was that the trial doesn’t answer whether switching early is better than switching at progression. As FDA reviewer Mirat Shah put it, “the biggest concern is that approving camizestrant would include the endorsement of a treatment paradigm that does not have established clinical benefit.” The agency also flagged the precedent risk, that biomarker-guided early switching could proliferate across tumor types without evidence it actually extends lives. Multiple ODAC members agreed that ESR1 mutation detection hasn’t been proven as a predictive biomarker (indicating treatment will help) vs. merely a prognostic one (indicating disease is worsening regardless). The patient representative was the most direct: “I really wonder if we are again exploiting the hope of women with metastatic breast cancer that somehow, if they’d known earlier, the trajectory of the disease would be different.”

The Truqap vote was more straightforward. CAPItello-281 showed radiographic PFS of 33.2 months vs. 25.7 months (HR 0.81) with capivasertib added to abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer. OS was immature (HR 0.90, not significant). FDA flagged toxicity concerns like hyperglycemia, rash, discontinuations, and deaths, and questioned whether the ~7.5-month PFS gain justified the added burden in an early, minimally symptomatic population. But the panel concluded that the unmet need in PTEN-deficient disease and evidence of target engagement were sufficient, with physicians expected to exercise discretion in patient selection. The single no-vote (Brian Rini, Vanderbilt) argued the benefit was too modest relative to the toxicity profile.

🧠 BPS Take: The split decision is less about two different drugs and more about two fundamentally different questions the FDA is wrestling with. The camizestrant vote was about whether the strategy of acting on a molecular signal before imaging shows progression is ready for primetime. The FDA essentially said: “you’ve shown that switching early extends PFS, but you haven’t shown it’s better than switching at progression, because you didn’t let the control arm access the drug”. That’s a very fair criticism, and I would be curious to see the communications between the FDA and AZN leading up to the launch of the study to better understand how far AZN strayed from the FDA’s guidance. Nonetheless, it is a novel effort by AZN to test switching upon ctDNA progression of a high frequency mutation. Pushing forth novel treatment paradigms is tough business and there are higher risks of their being bumps in the road. AZN may need to re-run this with a crossover-permitted design or wait for OS maturation, both of which cost lots of years and dollars.

What’s interesting is the contrast in how ODAC evaluated “meaningful benefit” across the two votes. In breast cancer, a 6.8-month PFS gain with a novel biomarker-guided paradigm wasn’t enough without OS. In prostate cancer, a 7.5-month PFS gain with an acknowledged toxicity burden passed 7-1. This feels like a broader commentary on where these two diseases are. Breast cancer has a deep bench of endocrine options and ODAC is fatigued by PFS-only approvals in that space, while PTEN-deficient mHSPC is a genomically defined population with genuinely limited options.

AZN will likely get the TRUQAP approval. For camizestrant, it wouldn’t be unprecedented for it to be approved in some fashion, however the negative ODAC vote, higher bar in breast cancer, and study design deficiencies pointed out in the meeting would make me think otherwise.

FDA Approves Arvinas’ Veppanu — First-Ever PROTAC Reaches Market, But Nobody Wants to Sell It

📅 May 1 | 🏢 Arvinas ( ), Pfizer ( ) | 💊 Veppanu (vepdegestrant) | 🏷️ Approval

The FDA approved Veppanu (vepdegestrant), a first-in-class PROTAC (proteolysis-targeting chimera), for second-line treatment of ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer. PROTACs work by hijacking the cell’s natural waste disposal system to degrade disease-driving proteins — a fundamentally different mechanism than traditional drugs that block or activate targets.

But the approval comes with an unusual asterisk. Neither Arvinas nor its partner Pfizer plan to commercialize it themselves. The two companies originally had a 50-50 development and commercialization deal signed in 2021, envisioning a broad ER+ breast cancer franchise. When VERITAC-2 data narrowed the addressable market to just ESR1-mutated patients in the second-line setting, the economics of the partnership collapsed. Pfizer, for whom a niche monotherapy doesn’t move the needle, effectively walked away from commercialization. Arvinas, which has laid off nearly half its workforce across two rounds of cuts in 2025 and has no commercial infrastructure, can’t launch it alone. In September 2025, both companies agreed to out-license commercialization to a third party. They submitted the NDA to FDA anyway. As of the approval date, no commercialization partner has been announced — CEO Teel says one is expected “in the coming weeks.”

🧠 BPS Take: This is a genuinely strange moment. The first PROTAC ever approved by the FDA has no one lined up to sell it. This should be a much bigger moment, but the commercial story is a cautionary tale about what happens when your data narrows your label to a sliver of your original thesis. Arvinas stock popped ~7%, but the company is clearly pivoting its identity toward its earlier-stage PROTAC pipeline in Parkinson’s (ARV-102), NHL (ARV-393), and KRAS-driven solid tumors (ARV-806). I’m curious to see who picks this asset up and for how much. There are not many de-risked assets in oncology up for sale, albeit this one being in a much smaller market than originally anticipated. For whoever picks up the commercialization rights, the question is whether a first-in-class PROTAC in a narrow ESR1-mutant niche can separate from existing oral SERDs and build a meaningful commercial business.

Intellia Posts First Positive Phase 3 for In Vivo Gene Editing — Stock Down ~7% Since

📅 April 27 | 🏢 Intellia Therapeutics ( ) | 💊 Lonvo-z (lonvoguran ziclumeran) | 🏷️ Data Readout

Intellia reported positive Phase 3 HAELO results for lonvo-z in hereditary angioedema (HAE), marking the first successful Phase 3 trial for any in vivo CRISPR gene editing therapy globally. A single dose of lonvo-z reduced HAE attacks by 87% vs. placebo (p<0.0001) over a six-month evaluation period. 62% of lonvo-z patients were completely attack-free and therapy-free vs. 11% on placebo. Safety was clean — all adverse events mild or moderate, no serious AEs in the treatment arm. Intellia has initiated a rolling BLA submission and is targeting a U.S. launch in H1 2027.

🧠 BPS Take: This is a historic milestone, no doubt. An in vivo gene editing therapy registered a positive Phase 3 study. But the market’s reaction (stock down 7% as of this writing) tells a more nuanced story. Specifically, I think it reflects the “cell and gene therapy tax”. Lonvo-z’s efficacy is essentially identical to Takeda’s Takhzyro (lanadelumab), which also delivers 87% attack rate reduction with a nearly identical mean monthly attack rate (0.26 for lonvo-z vs. 0.3 for Takhzyro). The difference is that lonvo-z is a single IV infusion (a one time potential cure) and Takhzyro requires injections every 2–4 weeks for life. How will the rest of the stakeholders in the market view this? If you’re Intellia, you want them to see this as a curative therapy for a very serious illness, something no other competitor can claim. But perhaps if you are a payer or a competitor, you can look at lonvo-z and say it’s mostly an expensive convenience advantage. The aforementioned “tax” shows up on the efficacy line of a cell or gene therapy’s therapeutic product profile. While the lifetime expense of getting this drug vs. taking several injections very two to four weeks, favors the one-time treatment, the near-term financing of a likely $400K+ gene-editing drug is a massive pill for any payer to swallow. Especially if the efficacy is not numerically all that different from cheaper (albeit lifetime) therapies.

For cell and gene therapies to justify the pricing and payer negotiation headaches that come with one-time treatments, the market increasingly expects a big shift in outcomes. For other gene editing companies, the lesson here is indication selection and product strategy planning early on, before you go down the road of committing to a lead clinical asset or pivotal program, is paramount.

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Intellia also announced a $180M equity raise at $10.75/share simultaneously with the data, diluting shareholders right at the moment of maximum attention. The science delivered exactly what it needed to. The question is whether the commercial math works in a world where matching existing efficacy with better convenience may not be enough to command gene therapy economics.

Summit’s Harmoni-3 Interim Miss Sends Stock Down 25% — Ivonescimab’s Global Story Gets Murkier

📅 April 30 | 🏢 Summit Therapeutics ( ) | 💊 Ivonescimab | 🏷️ Data Readout

The squamous cohort of Summit’s Harmoni-3 trial — evaluating ivonescimab (PD-1/VEGF bispecific) plus chemo vs. Keytruda plus chemo in first-line metastatic NSCLC — missed statistical significance on PFS at a recently added interim analysis. The independent data monitoring committee recommended the study continue as planned. Summit noted the interim had a “meaningfully higher bar” than the final PFS analysis due to minimal alpha spent. Final PFS and interim OS readouts are still expected H2 2026.

🧠 BPS Take: Summit tried to add an interim analysis to accelerate a potential FDA conversation, and the bet didn’t pay off. I generally think it is a red flag when companies start rejiggering their statistical analysis plan mid study. The high statistical bar (likely ~0.001 alpha) means this miss doesn’t necessarily predict failure of the final readout, but it does mean the PFS effect size in the global trial may be weaker than what Akeso showed in the China-only studies. This was a big fear behind the entire thesis of Summit as a company. They are playing the China clinical data arbitrage game, but will China data look as good in a global (more western) population? Folks like Kailera, who recently IPO’d, pushing this same strategy with a portfolio of Chinese GLP-1s should take note.

The stakes for the Harmoni-6 (China) OS update at ASCO’s plenary session just got significantly higher. If OS is strong, it buffers some of the negative sentiment from this latest PFS slip. However if the OS disappoints, the PFS slip starts to feel like the canary in the coal mine. Merck, BMS, Pfizer and others who have flocked to PD-1xVEGF are all watching closely.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

FDA Commissioner Makary Launches Real-Time Trial Monitoring Pilot

📅 Date: 2026-04-28 | 🏢 Company: POLICY/MACRO | 💊 Drug/Asset: N/A | 🏷 Event Type: FDA Policy / Regulatory Reform

The FDA announced two proof-of-concept real-time clinical trials (RTCTs) that are already running, plus a Request for Information (RFI) for a broader pilot program launching this summer.

AstraZeneca is conducting the Phase 2 TRAVERSE trial testing Calquence (BTK inhibitor) + AbbVie’s Venclexta + rituximab in treatment-naïve mantle cell lymphoma. The FDA confirmed it has already received and validated real-time safety signals from this trial through software company Paradigm Health. Amgen is running a Phase 1b trial of Imdelltra (tarlatamab), its DLL3 T-cell engager already approved for extensive-stage SCLC, in limited-stage small cell lung carcinoma (STREAM-SCLC).

The FDA receives aggregated signals only, including adverse event rates, tumor response percentages, and pre-agreed efficacy endpoints. No raw patient-level data. Individual records stay with the sponsor. FDA Chief AI Officer Jeremy Walsh: “We’re not interested in seeing that patient-level data. What we’re interested in is, can the FDA make a regulatory decision on signals?”

Commissioner Makary said 45% of the time between Phase 1 start and approval submission is “dead time” (i.e. paperwork, analysis, formatting, and the gaps between discrete phase). He framed this explicitly as a competitiveness issue: China surpassed the U.S. in Phase 1 trial volume around 2021, and the growth since has been “exponential.” The stated ambition goes beyond speed — it’s about collapsing the traditional Phase 1 → 2 → 3 sequence into “continuous trials” by eliminating inter-phase hiatuses.

🧠 BPS Take: This is the most concrete output of the Makary FDA push to modernize the agency and use technology to speed up drug reviews. Name-dropping AstraZeneca and Amgen signals credibility and that Big Pharma sees value in the transparency-for-speed trade. But the real test is whether this scales beyond these two oncology indications, how these scale up to larger studies, and later on into other therapeutic areas.

The China point Makary makes is an important one too. Seeing how quickly China has outpaced the US in clinical trials, as well as the plethora of deals by US based entities to bring-in Chinese drugs, is serving as a helpful counterpoint to show how our systems can be improved. It’s rare in our political culture to look at other countries and think, “hey they seem to know what they’re doing over there, let’s try that at home” from a place of abundance. Instead we respond best to competition. The fear that we are falling behind in drug development, AI, and energy comes from a place of scarcity, but perhaps America’s love language is competition, and China knows just how to pull on our heart strings.

The Lp(a) Drug Race: Novartis’ Pelacarsen (Lp(a)HORIZON, 8,323 pts), Amgen’s Olpasiran, Eli Lilly’s Muvalaplin — H1 2026 Outcomes Data Imminent

📅 Date: April 27, 2026 (feature week) | 🏢 Company: Novartis ( ) / Ionis ( ) / Amgen ( ) / Eli Lilly ( ) | 💊 Drug/Asset: Pelacarsen (ASO, Lp(a)HORIZON Phase 3); Olpasiran/AMG-890 (siRNA, OCEAN Phase 3); Muvalaplin (oral small molecule, Phase 3) | 🏷 Event Type: Industry Feature — Late-Stage CV Outcomes Race

CNBC highlighted three major pharmaceutical companies racing to prove that lowering lipoprotein(a) (Lp(a)) reduces cardiovascular events, with pivotal outcomes data expected in the first half of 2026. Novartis and Ionis are leading with pelacarsen, an antisense oligonucleotide (ASO), in the Lp(a)HORIZON trial enrolling 8,323 patients. Topline results are expected in H1 2026. Amgen is running the OCEAN(a)-OUTCOME Phase 3 trial with olpasiran, an siRNA. Eli Lilly is developing muvalaplin, an oral small molecule that inhibits Lp(a) formation, currently in Phase 3.

Approximately 64 million Americans have elevated Lp(a), and there is currently no approved therapy specifically targeting this risk factor. Elevated Lp(a) is an independent cardiovascular risk factor associated with increased rates of heart attack and stroke, even in patients with well-controlled LDL cholesterol.

🧠 BPS Take: The H1 2026 outcomes data from Lp(a)HORIZON is the pivotal proof-of-concept for the entire Lp(a) field. Lowering Lp(a) does not automatically equal reducing cardiovascular events, but most KOLs will tell you they feel pretty good that doing so will reduce cardiac events. Still, this needs to be be proven in a large, adequately powered outcomes trial. Lp(a)HORIZON with 8,323 patients is the first trial designed to answer that question. If pelacarsen hits, it serves as a sigh of rlief to the whole field, validating this target as a key lever for cholesterol control and opening the competitive gates for the rest of the Lp(a) programs to follow suit. If it misses, the conversation shifts to whether Lp(a) needs to be pushed down even further in order to see hard outcomes benefits. Right now pelacarsen has demonstrated 80% reduction in P2 studies. Olpasiran (Amgen) and Lepodisiran (Lilly) have shown 95% and 94% respectively.

Lilly again has a sharp strategy in this arena. They aren’t sticking to just siRNA based treatment, as they have an oral Lp(a) inhibitor, muvalaplin, now enrolling a P3 outcomes study. As we’ve seen with the PCSK9 market, it has taken a long time for injectables (whether they be antibodies or siRNA) to gain market traction. For cholesterol control, it’s possible oral convenience may hold the advantage for commercial uptake.

As an aside, I was pleased to see Lp(a) get attention on a more generalist site like CNBC. I feel pretty confident Lp(a) reduction is clinically meaningful. Just hearing so many stories from cardiologist friends of mine of very young people dying of heart attacks, not knowing why, only to later find out that they were genetically predisposed to having very high Lp(a). The annoying part about this is that even if these trials read out positively, it is going to take some time for guidelines to change and for clinical practice to change to regularly test for it. Right now, even for LDL, we just get our LDL-c measured in our annual checkups, when it is pretty clear that ApoB100 is a much better measure of your bad cholesterol related risk.

In any case, if you are curious about your genetic predisposition to high Lp(a), you can go pay for a test yourself (as I did) at the behest of one my cardiologist friends. South Asians and African Americans tend to be the most at risk, thus why I felt the need to get mine checked out. Thankfully I am A-OK, but even if I wasn’t, I am excited that there will be new drugs soon that help to prevent Lp(a) related cardiac events.

Semaglutide Cuts Heavy Drinking by 41% in Lancet RCT — GLP-1s Open Another Therapeutic Front

📅 May 1 | 🏢 Novo Nordisk ( ) | 💊 Semaglutide (Wegovy) | 🏷️ Data Readout

A randomized, double-blind, placebo-controlled trial published in The Lancet showed once-weekly semaglutide 2.4 mg reduced heavy drinking days by 13.7 percentage points more than placebo over 26 weeks in 108 adults with obesity and alcohol use disorder. Semaglutide also reduced total alcohol consumption (467.5 g/30 days difference), drinks per drinking day, self-reported cravings, and multiple alcohol biomarkers including phosphatidylethanol (p<0.0001). Safety was consistent with known GI side effects. The trial was conducted at Mental Health Center Copenhagen and funded in part by Novo Nordisk.

🧠 BPS Take: The anecdotal evidence has been accumulating for years. Now there’s a properly controlled Lancet RCT confirming it. GLP-1s reduce alcohol consumption. Importantly, this was a small trial (n=108), in patients with both obesity and alcohol use disorder, at a single site in Denmark. Less than 2% of people with alcohol use disorder in the U.S. use pharmacotherapy. If larger trials replicate this, Novo and Lilly have a potential indication that could expand GLP-1 addressable market well beyond obesity and diabetes into behavioral health. That’s exactly what Lilly is betting on with brenipatide, its once-monthly GLP-1/GIP agonist. The key question that remains for me is that will this still work in patients who are not obese? What does this say about breaking addiction to other vices that are not calorie-driven or food-like (e.g. smoking, opioids, etc.)?

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

M&A Bundle: Sun/Organon $11.75B (India’s Largest US Pharma Acquisition) + Lilly/Ajax $2.3B (Type II JAK2) + Ligand/XOMA $739M (Royalty Aggregation)

📅 Date: April 26-27, 2026 | 🏢 Company: Sun Pharmaceutical Industries / Organon ( ); Eli Lilly ( ) / Ajax Therapeutics; Ligand Pharmaceuticals ( ) / XOMA Royalty ( ) | 💊 Drug/Asset: Organon portfolio (Nexplanon, biosimilars, legacy brands); AJX-101 (Type II JAK2 inhibitor, Phase 1); XOMA royalty portfolio (200+ assets, 7 commercial) | 🏷 Event Type: Acquisition (All-Cash x2; Milestone-Based x1)

Sun Pharmaceutical Industries announced a definitive agreement to acquire Organon for $14.00 per share in cash, representing a 24% premium and an enterprise value of $11.75B. The deal, announced Saturday evening April 26, is India’s largest-ever acquisition of a U.S. pharmaceutical company. Organon’s portfolio includes Nexplanon (the #1 contraceptive implant in the U.S.), a biosimilars business, and legacy women’s health brands. The transaction is expected to close in early 2027, making Sun Pharma the third-largest global women’s health company.

Eli Lilly announced on April 27 that it will acquire Ajax Therapeutics for up to $2.3B in milestone payments. Ajax is developing AJX-101, a Type II JAK2 inhibitor in Phase 1 for myelofibrosis and polycythemia vera. Type II JAK2 inhibitors represent a mechanistic differentiation from all currently approved JAK inhibitors (ruxolitinib, fedratinib, pacritinib, momelotinib), which are Type I. This is Lilly’s sixth acquisition of 2026.

Ligand Pharmaceuticals announced on April 27 that it will acquire XOMA Royalty for $39.00 per share in cash, representing approximately a 3% premium and an equity value of $739M. The combined entity will hold royalty interests in over 200 partnered programs, including seven commercial products. The transaction is expected to close in Q3 2026.

🧠 BPS Take: Three completely different M&A logics playing out in the same 48-hour window.

Sun Pharma is making a bold move, signaling that they are not satisfied staying in India, and want to have a foothold in the US market and expanding its business into speciality areas, like women’s health. Raising $7.75B in debt to take out Organon could either be really smart or look really dumb in retrospect. Still, this is a major sign that one of India’s largest drug makers is ready to make waves in the US specialty market. Organon gives them a top-3 global women’s health franchise, a U.S. commercial infrastructure, and a biosimilars platform.

Lilly is buying yet another early clinical phase asset, this time a Type II JAK2 inhibitor for myelofibrosis. The idea here is that this strategy may overcome resistance mechanisms seen with Type I inhibitors (ruxolitinib, etc.). It still baffles me that for all the innovation we have had in oncology, myelfoibrosis is still treated largely with a series of slightly different flavors of JAK inhibitors. Nonetheless, here is Lilly continuing its trend of taking multiple shots on goal on early science well-before any of their GLP-1 patent cliffs hit. If AJX-101 shows activity in post-ruxolitinib myelofibrosis patients, this could quickly climb the JAK inhibitor hierarchy. If it doesn’t, Lilly writes off the milestones and moves on. A billion or two here and there as a write-off is just chump change for them.

Ligand/XOMA is pure financial engineering, aggregating royalty streams as an asset class. Post-deal, Ligand will have 200+ royalty assets generating predictable cash flows with minimal operational risk. These royalty businesses have done incredibly well and might be a win-win for later-stage biotechs, giving them a lifeline to large amounts of upfront non-dilutive capital. Notably Revolution Medicines did a royalty financing deal back in June 2025 with Royalty Pharma, netting them $2B upfront in exchange for tiered declining royalties on daraxonrasib for 15 years. The royalties drop to zero once annual sales exceed $8B. All signs point to them meeting or exceeding that mark. Owl Posting had a nice deep dive on these sorts of synthetic royalty deals and other methods of financial engineering in Biotech that I highly recommend reading if you want to learn more about this topic and how it fits into the broader architecture of innovation.

Triple Biotech IPO Surge: Seaport $255M (SPTX), Hemab $302M (COAG), Avalyn $300M (AVLN, +44% debut) — $850M+ Raised, Strongest Market Since 2021

📅 Date: April 27-30, 2026 (week) | 🏢 Company: Seaport Therapeutics ( ) / Hemab Therapeutics Holdings ( ) / Avalyn Pharma ( ) | 💊 Drug/Asset: Seaport neuropsychiatry pipeline (PureTech spinout); Hemab coagulation portfolio (Glanzmann thrombasthenia, Von Willebrand Disease); Avalyn inhaled IPF treatments | 🏷 Event Type: Triple Biotech IPO Pricing — All Three Upsized

Three biotech companies priced upsized IPOs during the week of April 27, collectively raising over $850M and signaling the strongest biotech IPO market since 2021. Seaport Therapeutics raised $255M by pricing 14.16 million shares at $18, upsized from an initial target of $212.4M. The company, a PureTech spinout, is developing a neuropsychiatry pipeline. Hemab Therapeutics Holdings raised $301.5M by pricing 16.75 million shares at $18, upsized from an initial target of $200M. The company, backed by Novo Holdings, is developing treatments for rare coagulation disorders including Glanzmann thrombasthenia and Von Willebrand Disease.

Avalyn Pharma raised $300M at $18 per share and surged 44% on its debut to close at $26, giving the company a market capitalization of approximately $1.1B. Avalyn, also backed by Novo Holdings, is developing reformulated inhaled treatments for idiopathic pulmonary fibrosis (IPF). The three IPOs bring Q1 2026 total biotech IPO proceeds to approximately $2.2B, according to industry trackers.

🧠 BPS Take: These three IPOs are a strong sign that the IPO window is open and public market investors have an appetite for mid to late stage drug companies again. A psych company, a pulmonary disease company, and a rare disease company, quite a diverse grouping, all doing well on their first days of trading is a signal that investors are willing to take risk across many therapeutic areas, and not just the hot areas like GLP-1s. Watch for more IPOs in Q2 2026 if this momentum holds.

Back next week with more BioPharma strategy takes! Share this with a friend of colleague if you found it helpful.

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