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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

The World Conference on Lung Cancer produced excellent relapsed small cell lung cancer data, and in the same week, the sharpest public argument yet about whether that kind of data can be believed. Two B7-H3 antibody drug conjugates cut the risk of death 54% against topotecan. But both trials ran in China only. Two sessions away, Gilead and Merck presented a frontline lung cancer study where the combination arm did slightly worse than the control overall (hazard ratio 1.07) and then showed that among Chinese enrollees the same combination cut deaths 45%. This doesn’t mean the Chinese data is wrong or fraudulent. The more likely explanation is that a China-only result is a promising signal, but companies have been buying these assets as though the signal were proof.

Then Summit presented a rebuttal at the same meeting. Their ivonescimab is the drug people have been skeptical about for exactly this reason. This week they reported updated global HARMONi data, and it held up in Western patients too. Hazard ratio 0.76 overall and 0.76 in the Western subgroup. This confirmation took an extra 14 months of follow up to get. Everyone else is still asking to be trusted. GSK committed up to $750 million to another Chinese trispecific this week, and five large drugmakers confirmed they are handing records to a House committee investigating trials run at Chinese military hospitals.

Novartis lost a fourth trial in a month, and separately lost something more durable. The FDA approved the first “radioligand equivalent,” a 505(b)(2) copy of Lutathera, eight years after the original. Novartis directs about 40% of its oncology research budget at radioligand therapy. So the first real threat to that franchise isn’t a better drug, but a company using a faster approval route to make a copy.

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BIOTECH/PHARMA NEWS 🧬

🔹 In KEYNOTE-D46/EVOKE-03, Trodelvy plus Keytruda produced a hazard ratio of 1.07 against Keytruda alone in frontline PD-L1-expressing non-small cell lung cancer, meaning the combination did slightly worse than the control, and the study was stopped. An exploratory analysis then found a 45% reduction in death risk among patients enrolled in China and 37% across East Asia. The drug and protocols were the same but the results differed depending on geography. Evercore ISI’s Umer Raffat said the result shows “why [the] Street has so much emphasis on U.S. trials,” and Leerink’s Daina Graybosch warned the preponderance of evidence points to China studies producing better survival than their global counterparts. Summit presented the rebuttal at the same meeting. Updated HARMONi data showed median overall survival of 16.8 versus 14 months, hazard ratio 0.76 (95% CI 0.61 to 0.95, p=0.0151), with the Western subgroup landing at the same 0.76 and 17.5 versus 14 months. The original April 2025 analysis had missed at 0.79, so it took fourteen extra months of follow up to confirm. Meanwhile GSK committed up to $750M to Chimagen for a myeloma trispecific, and Representative John Moolenaar said five large drugmakers are cooperating with his probe of trials at Chinese military hospitals.

🔹 Two B7-H3 antibody drug conjugates posted near identical wins against topotecan in relapsed small cell lung cancer. An antibody drug conjugate uses an antibody to find the tumor and deliver a chemotherapy payload directly to it, rather than flooding the whole body. Roche and MediLink’s tambotatug pelitecan, in TAISHAN-302 (n=451), reached median overall survival of 13.3 versus 9.4 months, hazard ratio 0.46 (95% CI 0.35 to 0.62, p<0.0001), with progression free survival of 7.4 versus 2.8 months and a response rate of 59.1% versus 9.7%. GSK and Hansoh’s risvutatug rezetecan, in the China-only ARTEMIS-008 (n=461), reached 18.5 versus 10.3 months, also hazard ratio 0.46, with progression free survival of 7.2 versus 3 months and a 58.3% response rate. Grade 3 or higher treatment-related adverse events were lower than topotecan in both (46.4% versus 74.7%, and 60.9% versus 78.2%), and interstitial lung disease ran 4.9% for tam-peli. Relapsed small cell lung cancer has had essentially nothing for thirty years, so a six fold response rate is the largest step the disease has taken in a generation. Both were presented by Chinese investigators from Chinese sites, which is the whole argument in one slide.

🔹 Novartis discontinued lifonebart (VHB937), a TREM2-stabilizing antibody, after the 251-patient ASTRALS Phase 2 trial missed both primary and secondary endpoints in amyotrophic lateral sclerosis (ALS). The primary endpoint was a composite of ventilator-free survival and change on the ALS Functional Rating Scale. An Alzheimer’s study continues, and full data goes to the ALS/MND symposium in Amsterdam on December 9-11. That’s the fourth failure in a month, after pelacarsen, del-desiran and the rap-cel holds. The more structural loss came a day earlier, when the FDA approved Curium’s Bexlutry, a lutetium Lu 177 dotatate injection cleared through the 505(b)(2) pathway as the first “radioligand equivalent” to Lutathera. That pathway lets a company rely partly on the original drug’s existing safety and efficacy data rather than running the full program from scratch. Novartis has sold Lutathera without competition since January 2018. Pluvicto and Lutathera together did about $2.8B last year and absorb roughly 40% of the oncology research budget. Novartis also paid $125M to Sironax for a blood-brain barrier delivery platform.

🔹 The FDA opened the Expedited Investigational New Drug Pilot on September 15 under “Operation Trialblazer,” offering 8 to 10 pairings between drugmakers and qualified academic centers or contract research organizations, with applications due Oct 30. The new feature is rolling review, where the agency evaluates pieces of an application as they arrive rather than waiting for a complete package, aiming to surface clinical hold issues early. Starting a trial in the US can take up to 2 years, against under 70 days in Australia, and Chinese trial registrations have gone from about 1,000 a year in 2010 to more than 5,000 in 2024 while the American figure sat near 3,500. The same week, STAT reported the FDA has secured 600 of the more than 2,200 hires it’s trying to make, with hundreds stuck in pre-onboarding because the centralized human resources center DOGE created is itself understaffed. Rolling review requires reviewers looking at submissions continuously rather than in one batch, which takes staff the agency doesn’t currently have.

🔹 The FDA approved ISEMBYLD (apitegromab-mstn) on Sept 13 for spinal muscular atrophy patients two and older who are already receiving an SMN2-targeted therapy. Spinal muscular atrophy is caused by a genetic defect that kills the motor neurons that signal muscles to contract, and every existing drug works on the neuron. This one works on the muscle instead, by blocking latent myostatin, a protein that limits muscle growth. It’s strictly an add-on. In the 188-patient SAPPHIRE trial the recommended 10 mg/kg dose produced a 2.2 point advantage on the Hammersmith Functional Motor Scale-Expanded (nominal p=0.0121), with 34.2% of treated patients gaining at least three points versus 13.5% on placebo. Fractures occurred in 9% versus 2%. Barclays downgraded the stock anyway and shares fell about 2.5% on the week. The skepticism is because an add-on layered on top of nusinersen or risdiplam has to justify a third payer conversation for a two point motor gain, and Scholar Rock hasn’t disclosed a price.

🔹 North Immunology raised $180M from Bain Capital, Janus Henderson and Deep Track Capital and will go public by merging into Aethlon Medical, with the startup’s investors holding 95.25% of the combined company and trading as NRTX from the first quarter of 2027. The asset, NOR-101, is a dual antibody hitting both IL-13 and IL-18 in atopic dermatitis, with Phase 1a beginning as it lists. Deep Track built the company itself rather than backing a founder. The same day, cardiometabolic developer Marea Therapeutics took over Lisata Therapeutics, a solid tumor biotech left stranded by a collapsed merger. Roughly two dozen biotechs have gone public this way in 2026. A structure that used to signal distress now carries crossover money and preclinical assets, which says the appetite for biotech risk has returned and the appetite for the IPO process has not.

🔹 Skyhawk Therapeutics’ once daily oral RNA splicing modulator SKY-0515 produced a 0.94-point improvement at 15 months in Huntington’s disease, against a 0.65-point decline in a matched natural history cohort. That’s a 1.59-point separation on a scale where 1.2 points is the accepted threshold for clinical meaningfulness. Higher doses cut mutant huntingtin protein by more than 60% and lowered PMS1 messenger RNA by 25%, and the separation reached significance at nine months and held at every later timepoint. No serious adverse events were reported. The weak part is the comparison. An external control drawn from a database isn’t a placebo arm, and Huntington’s progresses slowly enough that fifteen months of natural decline is a small number to beat. The Phase 3 FALCON program has finished enrolling 144 patients in Australia and New Zealand and is recruiting about 600 more globally. Roche abandoned tominersen in July and uniQure’s AMT-130 is at the FDA, so a once-daily pill would change the economics of the entire field.

🔹 Connect Biopharma’s IL-4 receptor alpha antibody rademikibart missed its primary endpoint in acute asthma exacerbations and the stock fell nearly 40%. What the company salvaged is specific. Lung function improved significantly at day 7, which is the endpoint it intends to make primary in Phase 3, alongside a 66% reduction in treatment failures and a 50% reduction in emergency department and unscheduled visits. Safety matched placebo. The strategy is to stop competing with Dupixent on chronic asthma control, where it would lose, and claim the acute exacerbation window instead, where no biologic is approved and speed of onset is the only thing that matters. That’s a coherent repositioning, and it rests on a secondary endpoint from a failed study, which the FDA will treat accordingly. The company is requesting alignment on a registrational program in both asthma and chronic obstructive pulmonary disease.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Front cover image source: Getty Images

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, please get in touch.

📩 For consulting inquiries, please email me.

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🛒 And make sure to check out our MERCH STORE.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Novartis’s bet on buying its pipeline instead of building it backfired this week. In just 8 days, the company lost the lead asset from a $12 billion acquisition of Avidity Biosciences this February, and also lost a cardiovascular outcomes trial that has been running for six years. The company also placed a voluntary halt on eight cell therapy trials on August 24 due to three patient deaths. Shares fell about 11% in a single session, the worst day in the company’s history. As of Thursday evening, several major financial institutions have downgraded the stock, mostly to Hold. Novartis’s shareholder Artisan Partners didn’t blame the CEO but criticized the board’s oversight of deals.

Novartis’s pelacarsen failure deserves a closer look, because it might be the most consequential result of the week. Lipoprotein(a) or Lp(a) is elevated in about one in five people worldwide, and Mendelian randomization studies have linked it to cardiovascular risk. Nobody had ever tested whether lowering it actually helps with outcomes. Novartis finally ran that test in 8323 patients, and the answer was no - even though Lp(a) came down, strokes and heart attacks didn’t. So either the theory is wrong, or the drug didn't lower Lp(a) enough. Amgen and Lilly each have a drug that cuts Lp(a) by more than 90%, and they think it’s the second explanation. The idea is that Lp(a) might only cause damage above a certain level, and 72% left patients still above it. Nobody knows whether this is the correct hypothesis, but Amgen and Lilly’s trials are still running.

Back in April, FDA’s oncology advisory committee voted 6 to 3 against approving AstraZeneca’s camizestrant, but they just approved it this week. The drug works differently than most cancer therapies. Normally you switch treatment when a scan shows the tumor has grown. With camizestrant, patients get regular blood tests looking for a resistance mutation, and you switch as soon as it appears, before any scan shows progression. The FDA panel objected because the trial never compared this approach against the standard one of waiting for a scan. Last week I covered internal memos showing a senior FDA official overruled her own review team on Replimune’s melanoma drug. It seems like the agency is weighing outside advice differently than it used to, at least in some cases.

Third, notice who published numbers this week. Roivant gave a p-value, Pharvaris gave an effect size, Beeline gave a response rate. Amgen, AstraZeneca and Bristol Myers announced three major oncology wins and gave nothing. The companies that published full numbers this week were mostly the smaller ones.

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BIOTECH/PHARMA NEWS 🧬

🔹 On September 4 Novartis’s pelacarsen missed its primary endpoint in an 8,323 patient cardiovascular outcomes trial. On Sept 8 del-desiran failed the Phase 3 HARBOR study in myotonic dystrophy type 1, missing on video hand opening time in roughly 150 patients dosed every eight weeks over 54 weeks. Both landed inside two weeks of the company halting eight trials of its rap-cel cell therapy after three patient deaths. Shares fell about 11% on Sept 9, the largest one-day decline on record, cutting market value by about 24B Swiss francs to roughly 215B. Del-desiran was the lead of three antibody oligonucleotide conjugates acquired with Avidity Biosciences for $12B at $72 per share, closed Feb 27. The surviving programs are del-zota, filed for accelerated approval with priority review in Duchenne muscular dystrophy, and del-brax in facioscapulohumeral dystrophy. Artisan Partners managing director David Samra told Reuters that “the party is over” and that successive chairmen had failed the company on acquisitions, while explicitly declining to blame chief executive Vas Narasimhan. Chairman Giovanni Caforio took the job last year.

🔹 The first outcomes trial ever run on an Lp(a)-lowering drug missed its composite primary endpoint of cardiovascular death, non-fatal heart attack, non-fatal stroke and urgent coronary revascularization requiring hospitalization. The trial ran 8,323 patients over six years, tested both the overall population at Lp(a) of at least 70 mg/dL and a subpopulation at 90 mg/dL, and gave everyone guideline-directed lipid and blood pressure therapy on top. Lp(a) came down. Events did not. Novartis’s chief medical officer Shreeram Aradhye said the findings did not demonstrate that lowering translated into reduced risk. Ionis fell 13.1% premarket and loses tiered royalties in the mid-teens to low twenties plus up to $650M in milestones. William Blair notes pelacarsen lowers Lp(a) about 72% while Amgen’s olpasiran and Lilly’s lepodisiran exceed 90%, leaving room for a threshold effect. Citi would “not declare the mechanism dead” but wants full data to separate a near-neutral result from a directional miss. Full results come at a medical meeting.

🔹 The FDA granted accelerated approval to camizestrant, branded Etcamah, on Sept 4, combined with a CDK4/6 inhibitor for hormone receptor positive, HER2 negative advanced breast cancer once an ESR1 mutation is detected during first line therapy. This is the first cancer approval triggered by a resistance mutation found in circulating tumor DNA before imaging shows the disease progressing. In SERENA-6, 315 patients switched on the blood result and reached median progression-free survival of 16 months versus 9.2 months (hazard ratio 0.44, 95% CI 0.31 to 0.60, p<0.00001). Overall survival was immature. The Oncologic Drugs Advisory Committee voted 6-3 against in April, objecting to a nonstandard time zero, no evidence that mutation-guided switching beats waiting for actual progression, and no crossover. The label carries a boxed warning for QTc prolongation (heart rhythm problem).

🔹 Amgen’s Imdelltra (tarlatamab) plus AstraZeneca’s Imfinzi (durvalumab) improved overall survival at a planned interim analysis of DeLLphi-305, a 563-patient open label trial of first line maintenance in extensive stage small cell lung cancer after chemotherapy and durvalumab induction. Progression-free survival and response rate also hit. This is the first checkpoint inhibitor plus T cell engager combination to extend survival in the setting. Median survival with current care is about one year and only 3.6% of these patients are alive at five years. Dana-Farber’s Jacob Sands called the results among the most compelling he has seen. Neither company released a hazard ratio, a median or a confidence interval. The same day, BMS said arlo-cel met its primary endpoint of response rate in the registrational QUINTESSENTIAL trial, which would make it the first GPRC5D-directed CAR-T in quadruple-exposed myeloma, and released no response rate. These are changing claims, but no numbers to check any of them against.

🔹 Regulators placed a partial clinical hold on RISE-2, a late stage focal epilepsy study of Biohaven’s opakalim (BHV-7000), after rodent studies turned up a drug-related metabolite the agency wants explained. Enrolled patients keep dosing, recruitment stops. RISE-3, fully enrolled, is unaffected. Biohaven licensed the Kv7 channel opener to SK Biopharmaceuticals in late August for $350M upfront and up to $795M in total value, and analysts had flagged RISE-2 as likely necessary to support a filing. Biohaven says it disclosed all clinical and nonclinical data before signing and that SK was comfortable with the metabolite. RBC’s Leonid Timashev warned the hold “adds risk” and that the requested data could surface a concerning signal. Shares fell more than 10% and RBC downgraded the stock. Biohaven has now had a rare disease rejection, a spinal muscular atrophy failure and a depression within the past 12 months.

🔹 Beeline Medicines launched in April on a $300M Series A, built entirely around five programs Bristol Myers had shelved. The bet was that big pharma drops assets for portfolio reasons rather than scientific ones. This week, Afimetoran, an oral once daily inhibitor of Toll-like receptors 7 and 8, beat placebo in all three dose groups in a phase 2 lupus trial, with p<0.001 at every dose and safety matching earlier studies. They are heading into pivotal trials in both systemic and cutaneous lupus. Lupus has broken more drug programs than almost any other disease, so a clean dose ordered result there is a real signal. And the model is spreading. Kura Oncology did something similar this week, spinning its own diabetes work into a new company called Caspian Therapeutics with $50M and Lilly backing it.

🔹 Roivant reported Phase 2 results in pulmonary hypertension associated with interstitial lung disease, a condition where scarring in the lungs drives up blood pressure in the pulmonary arteries and the heart eventually fails trying to push against it. Their inhaled drug mosliciguat cut pulmonary vascular resistance by 56.3% placebo-adjusted at week 16 (p<0.0001), a 51.3% drop on drug against a 6.6% rise on placebo, in 135 patients across 87 sites in 20 countries. 6 minute walk distance improved 35.2 meters at week 16 (p=0.0027) and 52.7 meters at week 24, with NT-proBNP down 53.2%. Roivant says the resistance number is the largest reduction reported in any randomized controlled pulmonary hypertension trial. The commercially important detail is tolerability. Cough occurred in 12.1% on drug versus 18.2% on placebo, in a market where the cough burden from inhaled treprostinil is the standing complaint. Shares rose 19%. The Phase 3 PHrontier study is enrolling about 375 patients. A Phase 2 hemodynamic effect this large has failed to translate before, but rarely with the walk distance moving alongside it.

🔹 Pharvaris’s oral bradykinin B2 receptor antagonist deucrictibant extended-release reduced monthly attack rates by 83% versus placebo over 24 weeks in hereditary angioedema prophylaxis, rising to 87% in patients with type 1 or type 2 disease, across 85 patients. Every secondary efficacy endpoint hit statistical significance and adverse events were mild to moderate. Filings begin in the first half of 2027. This is the second pivotal win for the molecule, which already has an on-demand application under FDA review, and it puts a once daily pill against injectables in long term prevention. The same week, Intellia’s lonvo-z, a one time in vivo CRISPR treatment for the same disease, was accepted for priority review with a March 10, 2027 target date and no advisory committee planned. Patients with a lifelong genetic disease are about to be offered a daily tablet or a single infusion, and nobody knows yet which one they want.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Front cover image source: Fabrice Coffrini/Agence France-Presse/Getty Images

Biotech’s next frontier

Genomic medicine is at an inflection point. What comes next has even the skeptics feeling hopeful.

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🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, please get in touch.

📩 For consulting inquiries, please email me.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

You may remember the Replimune Tudriqev drama from this July and August. The company had already gotten two complete response letters in the past, but this time the drug was approved by the FDA. On Wednesday, internal FDA memos were released and showed that Asha Das, director of the biologics center’s office of clinical evaluation, overruled her review team to give Tudriqev accelerated approval on August 6 even though the reviewers wanted to reject it for the third time. Last week, I reported on Revolution Medicines’ Rasonque receiving approval in just 35 days under the Commissioner’s National Priority Voucher. Two different stories, but both show regulatory outcomes drifting away from the evidence and toward whoever holds seniority. This is pretty hard to underwrite.

The second theme this week is China. GSK paid Hutchmed $110 million upfront for a preclinical EGFR-KRAS conjugate, Roche paid Simcere $75 million upfront for a trispecific T cell engager, and Akeso’s ivonescimab beat Keytruda on overall survival in a China-only Phase 3. In the same week, the acting heads of CDER and CBER plus the directors of the device center and the Oncology Center of Excellence published a commitment to expand foreign site oversight and add inspectors at the agency’s China offices, after reporting surfaced three deaths in Chinese trials that were never disclosed when they happened. Big pharma keeps buying Chinese assets, and the FDA is now openly acknowledging it can't inspect most of the trials behind them.

The third theme is what companies are willing to tell you. Akeso and Summit announced an overall survival win against the biggest drug in oncology and published no hazard ratio, no median survival and no enrollment number. Novartis announced two positive Phase 3 multiple sclerosis trials with no annualized relapse rate. Ultragenyx announced a Phase 3 failure and disclosed no effect sizes either, which is the newer development. The practice has spread from wins to losses. The exception this week was AbbVie, which put out a full CERVINO table with a hazard ratio, a confidence interval, a p-value and grade by grade safety.

Finally, Trump’s most favored nation pricing reached the mid cap biotechs. Nine companies signed, and the discounts land in Medicaid in exchange for protection in Medicare and from tariffs. Medicaid is where prices were already lowest.

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BIOTECH/PHARMA NEWS 🧬

🔹 Newly released agency documents show that Asha Das overrode her review staff in granting accelerated approval to Tudriqev plus nivolumab on Aug. 6, four days past the PDUFA date and eight days after a 10-3 favorable advisory committee vote. The review team had recommended rejection, which would have been the third complete response letter in 13 months after July 2025 and April 2026, both over whether the single arm IGNYTE data could show the oncolytic virus contributed anything on top of nivolumab. The approved label already encodes the reviewers’ objection. The efficacy population is 91 patients with at least one noninjected lesion, response rate 24.2%, median duration 14.1 months, not the 33.6% and 24.8 months that advisory committee voted on. What’s interesting and new here is the documentation of a formal internal disagreement resolved by seniority.

🔹 GSK licensed Hutchmed’s HMPL-A830 for $110M upfront and up to $1.19B in milestones and royalties, taking global rights outside mainland China, Hong Kong, Macau and Taiwan for an antibody-targeted therapeutic conjugate that links an EGFR antibody to a KRAS-blocking small molecule payload, entering the clinic this year. Roche followed with $75M upfront to Simcere Zaiming for a preclinical trispecific T cell engager, its second China deal in two weeks. Simcere has now signed five licensing deals since early 2025 worth up to $5.66B. Days later, four FDA center leaders published an editorial committing to more Bioresearch Monitoring inspectors in China, remote assessments, reviewer training to flag problem sites, and public disclosure when human-subject concerns arise. Their instruction to sponsors was blunt: treat the inability to inspect or access data as a material factor in regulatory strategy. China ran under 8% of global trials in 2010 and passed the United States on annual registrations in 2020.

🔹 Reporting this week detailed three deaths in Chinese investigator-initiated trials that were not disclosed when they occurred. A boy died in Aug 2025 after a HuidaGene CRISPR therapy for Duchenne muscular dystrophy, with public updates on the trial halted for more than a year. A 6 year old girl died after brain-targeted gene editing at Xinhua Hospital, and her death was never announced. The investigators published their results without it. And a man in his 50s with systemic sclerosis died in March 2026 after RiboX’s in vivo CAR-T, five months before the FDA cleared that program in August. Representatives John Moolenaar and Ben Cline have asked the agency to reject China-generated data unless sites are audited annually. There’s a scientific thread underneath the regulatory one. Two of these deaths involved viral delivery of gene editors, an approach US researchers had largely moved away from over exactly these safety concerns. The regulatory question is whether an investigator-initiated trial in a country the FDA can’t readily inspect should feed a US filing at all.

🔹 The White House announced agreements with Alcon, Astellas, BeOne Medicines, BridgeBio, CSL, Kyowa Kirin, Sun Pharma, Teva and UCB on August 31, with Incyte signing separately. Each aligns outpatient prices for state Medicaid programs to the lowest rate charged abroad through the CMS GENEROUS model, which expires in 6 years. In exchange the companies are exempt from most favored nation pricing in Medicare and from Section 232 pharmaceutical tariffs, and they will list on TrumpRx. Collectively they committed at least $19.6B to US manufacturing, and the administration projects more than $600B in savings. The math is less generous than that. Medicaid has had mandated steep statutory rebates since 1990, Medicaid drug spending was $54B in 2024 against Medicare’s $163B, and RBC’s Brian Abrahams notes Medicaid is under 2% of sales for BridgeBio’s Attruby. Manufacturers traded a discount in their smallest channel for protection in their largest one.

🔹 The FDA approved Mimrylo (rusfertide) on August 28 for erythrocytosis in adults with polycythemia vera, the first hepcidin mimetic of any kind. It’s a once weekly subcutaneous peptide that restrains red cell production through iron regulation rather than suppressing the marrow. In the Phase 3 VERIFY trial, 293 phlebotomy-dependent patients were randomized to rusfertide or placebo on top of standard care, and 76.9% of rusfertide patients achieved a clinical response during weeks 20 through 32. Protagonist discovered the molecule and ran it through Phase 3. Takeda holds global rights. The day before, Lisraya (brepocitinib) became the first oral therapy approved for dermatomyositis, a JAK1 and TYK2 inhibitor from Priovant, on the strength of VALOR, a 241-patient trial of 15 mg, 30 mg and placebo that read out in the New England Journal of Medicine in March and added skin endpoints in JAMA Dermatology last month. Two rare diseases, two mechanisms nobody had approved before, and no advisory committee for either.

🔹 Ultragenyx’s intrathecal antisense oligonucleotide apazunersen, designed to unsilence the paternal UBE3A allele in Angelman syndrome, missed its primary endpoint of change from baseline in the Bayley-4 cognitive raw score, and its key secondary of net response on the Multidomain Responder Index. Ultragenyx reported no differences between treated and control groups on the index or on mean changes across its five component endpoints, and released no effect sizes at all. Safety matched Phase 1/2. Shares fell 44.8%. Consensus had carried peak sales above $1.8B. Leerink’s Joseph Schwartz said the company’s language “leaves very little room for an optimistic interpretation” and that the investment case has shifted from pipeline to commercial execution. His revised peak estimate for UX111 in Sanfilippo syndrome is $120-$240M. Ultragenyx is weighing significant expense reductions and still targets profitability in 2027. Ionis fell 4% in sympathy. The Phase 1/2 signal here was strong enough to convince everyone, and that’s the lesson. Open label neurodevelopmental gains don’t survive a sham control.

🔹 A prespecified interim analysis of Akeso and Summit’s HARMONi-2 trial met the key secondary endpoint of overall survival against pembrolizumab monotherapy in first-line lung cancer patients with PD-L1 tumor proportion score of at least 1%, per the independent data monitoring committee. No hazard ratio, no median survival and no enrollment figure were released. UBS’s David Dai estimated roughly a 24% relative reduction in risk of death, which is an analyst’s guess rather than data. Summit rose as much as 18%, Akeso closed up 3% in Hong Kong. This is the survival result the class needed after the 2024 progression-free survival win left the question open and HARMONi-6 drew arguments about how Chinese patient characteristics translate. It’s still a China-only trial, and US approval rests on the global HARMONi program, whose survival data are expected in 2028. Beating Keytruda head to head anywhere is a genuine event. Doing it without publishing a single number is this week in miniature.

🔹 AbbVie’s B cell maturation antigen T cell engager etentamig cut the risk of progression or death by 60% versus investigator’s choice of standard therapy in 393 patients with a median of three prior lines of relapsed/refractory multiple myeloma. Progression free survival hazard ratio 0.40 (95% CI 0.29 to 0.54, p<0.0001), response rate 74.0% versus 45.7% (p<0.0001), 12 month overall survival 87.9% versus 72.0% (HR 0.48, nominal p=0.0012) at 11.4 months median follow up. Cytokine release syndrome occurred in 28.3%, almost all grade 1, with no grade 3 or higher events and 0.9% grade 1 neurotoxicity. Grade 3/4 infections ran higher than control at 27.7% versus 19.2%, but fatal infections were lower at 1.5% versus 3.1%, and discontinuations were 3.6% versus 9.6%. AbbVie will discuss next steps with regulators.

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Have a great rest of your week and thanks for reading Biotech Blueprint!

DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Front cover image source: Madeline Monroe/C&EN/Shutterstock

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, please get in touch.

📩 For consulting inquiries, please email me.

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🛒 And make sure to check out our newly launched MERCH STORE.

Yesterday, I published a new podcast episode in collaboration with on the Moderna/Merck Phase 3 individualized neoantigen therapy. We get into why melanoma was first cancer picked, why the kidney cancer trial will be the real test, and the machine learning algorithm that selects the neoantigens, which may turn out to be the most interesting regulatory question of the whole thing.

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VIDEO SUMMARY

Today’s video has a surprise co-host who invited himself to do the intro :) I didn’t notice until the edits.

THIS WEEK’S KEY TAKEAWAYS 🔑

Another busy week in biotech and pharma. The FDA approved Rasonque (daraxonrasib) on August 26, ONLY 35 days after accepting the application on July 22. The application went through the Commissioner’s National Priority Voucher pilot, which aims to go from application to approval in just 1-2 months, and Revolution Medicines is now selling the first broadly RAS-targeted medicine in metastatic pancreatic cancer at $39,800 per 30 day supply.

In contrast, two days before the approval, the FDA told Capricor its Duchenne cell therapy needed three more months, pushing decision for deramiocel from August 22 to November 22 after an amendment that reframed the indication around upper limb function instead of cardiomyopathy. Capricor’s stock rose 29% on the delay, because the alternative that most analysts expected was rejection. The FDA is reviewing some drugs in five weeks and pushing others back by months. The market is now treating that difference as information to trade on.

The second theme this week is that pricing pressure might be moving down to smaller companies. The White House is expected to announce Most favored nation agreements with several mid-size biotechs as early as Monday. This will likely extend the same structure 17 large pharma companies have already signed, including discounts to state Medicaid programs benchmarked to foreign prices, in exchange for a three year exemption from tariffs.

Companies are increasingly disclosing less information. Lilly has pulled Phase 1 programs from its published pipeline and stopped disclosing most deal values. Moderna’s personalized cancer vaccine selects 34 neoantigens per patient out of thousands of tumor mutations, and the algorithm doing the selecting is proprietary, as is the hazard ratio from the Phase 3 that moved the stock 177% on Aug 19. On August 27 Moderna announced a $2 billion private placement of convertible senior notes due 2032, zero coupon, with capped calls struck at least 150% above the reference price. So a readout that included no effect size at all became two billion dollars of cash at a valuation nobody outside the company can independently check.

Lastly, Genentech paid $190 million upfront in a deal worth up to $2.3 billion for a Korean obesity candidate with a non-incretin mechanism, and Akeso’s ivonescimab beat AstraZeneca’s Imfinzi in a China-only Phase 3.

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BIOTECH/PHARMA NEWS 🧬

🔹 The FDA approved Rasonque (daraxonrasib) on Aug 26 for adults with metastatic pancreatic adenocarcinoma who have had at least one prior systemic therapy or who can’t tolerate multiagent chemotherapy. RASolute 302 randomized 500 patients 1:1 to daraxonrasib 300 mg once daily (n=248) or chemotherapy (n=252). Median overall survival was 13.2 months versus 6.7 months, hazard ratio 0.40 (95% CI 0.30-0.53, p<0.0001). Median progression-free survival was 7.2 versus 3.6 months, response rate 31.6% versus 11.2%. The RAS G12-mutant subgroup and the overall population produced nearly identical curves, which is the mechanistic point. This drug inhibits the active, GTP-bound form of RAS broadly, rather than targeting one G12C allele the way earlier KRAS drugs did. That’s why those earlier drugs never became large franchises and why RBC Capital Markets models $11.5B in peak sales here. The label warns on dermatologic and soft tissue toxicity, stomatitis, diarrhea, gastrointestinal perforation and interstitial lung disease, with prophylaxis recommended from day one. More than 2,000 patients had already received the drug through expanded access, so the launch starts with a prescriber base already in place. Second-line metastatic pancreatic cancer has never had a targeted option before this.

🔹 The administration is expected to announce Most favored nation pricing agreements with several mid size biotechs as early as Monday, extending a template that 17 large pharma companies have already signed, including Pfizer, Lilly and Amgen. The deal is outpatient discounts to state Medicaid programs benchmarked to what the company charges abroad, with state participation optional, in return for a three year exemption from pharmaceutical tariffs. For a large company that’s a rounding error against tariff exposure. But this can be much more consequential for a single-product mid cap biotech because it permanently resets the US net price while the tariff relief expires after three years.

🔹 Moderna announced a proposed private placement of $2B of convertible senior notes due 2032 on Aug 27, with a $300M upsize option, for oncology investment and debt repayment. The notes bear no regular interest, the principal doesn’t accrue, and capped calls set the effective dilution cap at a premium of at least 150% to the reference price. Shares fell about 5%. What makes this interesting is the sequencing. On August 19 Moderna gained 177% on an interim Phase 3 in resected melanoma reported with no hazard ratio, no p-value and no confidence interval. Eight days later, that stock move became financing. Zero coupon paper struck 150% above a price the market set on incomplete information is a very good trade for Moderna and a leap of faith for whoever buys it. Meanwhile Lilly has stopped publishing itsphase 1 pipeline and most deal values, and the neoantigen-selection algorithm behind Moderna’s vaccine stays undisclosed to the researchers being asked to evaluate it.

🔹 Roche’s Genentech licensed worldwide rights outside South Korea to Hanmi Pharmaceutical’s HM17321 on Aug 24 for $190M upfront, up to roughly $2.3B in milestones, and tiered royalties. HM17321 is a urocortin-2 analog, a non-incretin mechanism designed to drive weight loss while preserving lean mass. Incretin therapies deliver 15% to 25% total body weight reduction, but a meaningful fraction of that loss is lean tissue. The next competitive front in obesity is body composition rather than the headline weight loss percentage. Hanmi cleared a US investigational new drug application in Nov 2025 and is running Phase 1. Genentech takes over from Phase 2.

🔹 The full CARDIO-TTRansform results landed ahead of the European Society of Cardiology Congress and finally explain the July miss. In 1,432 patients randomized 1:1 to eplontersen 45 mg or placebo subcutaneously every four weeks across 130 sites in 20 countries, the composite of cardiovascular death and recurrent cardiovascular events through week 140 was not met. In patients not on a transthyretin stabilizer, the hazard ratio was significant at 0.71. In patients already on a stabilizer at baseline, which was 57% of each arm, plus another 24% who started one mid trial, there was no treatment effect at all. The plain reading is that once tafamidis or acoramidis is already stabilizing the protein, adding an injectable silencer on top doesn’t help much. That’s a commercial problem more than a biology problem, because the stabilizer-naive population shrinks every quarter. It also sets up a hard test for Alnylam, whose vutrisiran analyses and next gen nucresiran Phase 3 TRITON-CM both go on display in Munich starting Friday. Alnylam argues greater potency and a different trial design will separate it from eplontersen.

🔹 Spyre Therapeutics’ anti-TL1A antibody SPY072 missed its internal bar in a 143 patient, 12 week, placebo-controlled Phase 2 in rheumatoid arthritis. The lower dose reached statistical significance with a 1.9-point reduction in disease activity against 1.3 points for placebo. The higher dose missed the primary objective outright, and that’s what really matters, because a dose response that inverts is hard to interpret as a genuine drug effect. Safety was comparable to placebo. The stock fell 13% and gave up more than $1B of a market capitalization above $9B. TL1A is the target Merck bought Prometheus for, and that Sanofi and Roche both paid up to enter, all on inflammatory bowel disease data. It doesn’t automatically translate to rheumatoid arthritis, where the bar is a crowded field of drugs that already work well. Psoriatic arthritis and axial spondyloarthritis data come in the fourth quarter. The IBD case for TL1A is still fine. The case that it works across every inflammatory disease is not.

🔹 Akeso and Summit’s HARMONi-GI1 trial stopped early at a prespecified interim analysis after ivonescimab plus chemotherapy beat durvalumab plus chemotherapy on overall survival in previously untreated advanced biliary tract cancer, with progression and response endpoints also met. This is the first therapy to beat a checkpoint inhibitor + chemotherapy regimen on survival in this setting, and the first positive Phase 3 for the PD-1 by VEGF bispecific outside lung cancer. Summit rose 14%. However, the trial ran entirely in China, which is a real question for a US filing given how the FDA has handled single country oncology datasets. And no hazard ratio, median survival or patient count came with the announcement, which is becoming routine. Biliary tract cancer is a small indication, so the commercial value here is limited. What matters is the evidence that the mechanism generalizes beyond non-small cell lung cancer, where the ivonescimab argument has been stuck for two years.

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Have a great rest of your week and thanks for reading Biotech Blueprint!

DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Front cover image source: WSJ

Hartaj (author of ) and I recorded this episode on August 20, 2026, the day after the Phase 3 INTerpath-001 trial read out, while the stock was still moving. A week later we still don’t have a single number from the trial itself, but the market has somewhat settled. I also wanted to fill in a few things we ran out of time to mention on the episode.

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, please get in touch.

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WHAT HAPPENED

We decided to record this episode because on Aug 19, Moderna and Merck announced that intismeran autogene (mRNA-4157/V940), Moderna’s mRNA individualized neoantigen therapy (INT) built for each patient from the mutations in their own tumor + Merck’s Keytruda (pembrolizumab), succeeded in a Phase 3 trial. The trial, INTerpath-001, enrolled 1,137 patients whose melanoma (stage 2b through 4) had been surgically removed but who were at high risk of it returning. Everyone received Keytruda, which is the current standard of care and two thirds also received INT on top. Adding it meant longer before the cancer came back, and longer before it spread to distant organs. This was the first positive Phase 3 for any INT, the first for any mRNA cancer therapy, and the first time anything has beaten Keytruda alone in this setting. The companies released no effect sizes, no hazard ratios and no survival curves. Overall survival data are still being collected.

WHY OLD CANCER VACCINES FAILED

I gave a short version of this on the episode. The longer version is more nuanced and interesting.

For 30 years, cancer vaccines targeted tumor-associated antigens like MAGE-A3, MUC1, NY-ESO-1, PSA, gp100. These are self proteins that tumors overexpress. And self proteins are presented in the thymus during development, where the T cells capable of recognizing them with high affinity are deleted on purpose. This is called central tolerance and happens to prevent autoimmune disease.

So those trials were failing not because vaccination doesn’t work against cancer, but because the immune system had already been trained early in life to ignore the exact targets we were pointing at. The only T cells left to recruit were the low-affinity ones that slipped through the early selection in the thymus.

A neoantigen has never been seen in the thymus because it’s created by a mutation in that specific tumor, long after selection finished. So there is no tolerance to it, and the high affinity T cells are still there. That is the shift.

WHY THE PHASE 3 MATTERS

The phase 2b hazard ratios, 0.51 for recurrence-free survival (RFS) and 0.411 for distant metastasis free survival (DMFS). RFS measures the time after treatment without any cancer return, while DMFS tracks the time without cancer spreading to distant organs or the patient dies, and both positively trend with overall survival (OS). The Phase 2b topline came in December 2022, and the five year follow-up was presented at ASCO this June, but the trial was small (n=157). That is why the confidence interval on the RFS hazard ratio ran from 0.294 all the way to 0.887. The data were compatible with a halving of risk, and also with a fairly modest benefit.

INTerpath-001 enrolled 1,137 patients with surgically removed stage 2b to stage 4 melanoma. This should solidify some of those uncertain numbers from the earlier phase.

It's also important to mention that INTerpath-001 met its endpoints at a pre-specified interim analysis, which means the effect crossed an early boundary. The trial itself continues, and OS is still maturing. Crossing an interim boundary is itself a positive sign, since it means the effect was large enough to be convincing early. But effects measured at those boundaries can be inflated, because the boundary gets crossed precisely when random variation has pushed the estimate furthest ahead. That is not a criticism of the trial, it is just how sequential testing works.

THE ESCAPE ROUTE WE DIDN’T DISCUSS

In the podcast, we covered PD-L1 upregulation as the tumor’s counterattack, and epitope spreading as the bonus.

A third thing we didn’t get to in the podcast that I think could be important for INT has to do with a molecule called MHC class I. MHC class I is a cell surface protein found on almost all cells that presents protein fragments to CD8+ cytotoxic T cells to signal infection or abnormality like a tumor antigen.

To work properly though, the MHC class I molecule requires beta-2 microglobulin (B2M), which is a small protein. And B2M is encoded by a single small gene that when lost the cell presents nothing at all, to any T cell, regardless of what the vaccine encodes. B2M mutations (and HLA loss of heterozygosity) are documented mechanisms of acquired resistance to checkpoint blockade in melanoma specifically.

Encoding 34 neoantigens makes it very hard for a tumor to escape by losing targets one at a time, but this global route could essentially push selection toward tumors that have exited antigen presentation entirely.

If relapses in the treatment arm are enriched for MHC class I defects compared with the control arm, that is evidence the vaccine applied real pressure.

This isn’t a reason to doubt the results or be less excited about the full data from INTerpath-001. It is just an interesting piece of immunology that might complicate things for this INT down the road.

INTISMERAN IN THE CLINIC

Speaking of potential complications, one thing I think about is how this vaccine is going to work in the clinic and the logistics surrounding it. Reported turnaround for intismeran is about six weeks from tumor sample to dose, which is impressive. But it requires adequate tumor tissue, chain of custody, sequencing, manufacturing and scheduling to line up for every single patient. Most adjuvant melanoma is treated in community oncology practices, not academic centers with dedicated coordinators for this kind of thing. That might represent a real operational problem, at least at first.

We have seen this before with Provenge (sipuleucel-T), the first approved therapeutic cancer vaccine that extended survival in metastatic prostate cancer when it was approved in 2010. It also cost around $93k a course. It was difficult to manufacture, and uptake never took off. This is why the manufacturing and delivery side deserves as much attention as the immunology.

THIS WEEK IN NUMBERS

The market probably was not pricing most of this. It was pricing something simpler, which is if it works in melanoma, it might work in the other tumor types too.

closed at $62.96 on Tuesday, Aug 18. On Wednesday, it closed at $174.38, up 177%, the largest one day percentage gain ever recorded by an S&P 500 company in at least 25 years. Then Thursday, Aug 20, it fell 23% to $133.32 likely as people took profits before recovering to $145.13 on Friday. Since then we saw the stock trading at $138.89 on Monday and a 13.6% jump on Tuesday, Aug 25, possibly helped by Wolfe Research upgrading the company from “Underperform” to “Peer perform.”

Market cap now sits around $63 billion, up from roughly $25 billion nine days ago.

The give back was partial, and the repricing has already happened. BofA moved off Underperform on the 20th and said the story had fundamentally changed. Goldman, Morgan Stanley, and Barclays all followed within four trading days.

I think it’s interesting that nobody has issued a Buy and the average price target across recent notes sits around $87, with a high of $170 and a low of $25. That spread is enormous and tells us that banks disagree whether this is a platform company or a melanoma company, and analysts are being cautious until more data arrives. I would also expect a move if they confirm the data is being presented at ESMO 2026 in October and potentially a dip if these data do not show up in Madrid. Nothing has been announced as of Aug 26.

WHAT TO WATCH FOR

All of this is to say that I am excited. Not because a stock tripled, but because the tolerance problem is the one that broke this field for 30+ years, and this looks like the first time anyone has solved it. If that holds up in the other tumor types, it matters well beyond melanoma.

ESMO runs October 23 to 27 in Madrid. The late-breaking abstract deadline is September 8. ESMO's own Scientific Committee co-chair wrote “come to see this data!!” on X about the readout. Did she indirectly confirm Moderna is presenting, or is she applying a bit of public pressure to get them there?

Episode is live now. Thanks as always for listening.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Front cover image source: Dana-Farber Cancer Institute

Viral vector, meet lipid limousine

These nanoparticles have become key vehicles in genomic medicines and vaccines. What makes them so useful?

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🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, please get in touch.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Moderna gained 177% on Wednesday, closing at $174.38 and adding about $44 billion of market value in a single day. This is the largest one day gain by any S&P 500 company this century. Short sellers lost about $5 billion, and the stock fell over 23% on Thursday.

When I saw the chart on early Wednesday morning, I thought it was a glitch.

The jump is based on a Merck-Moderna press release saying a Phase 3 melanoma “vaccine” trial met its primary endpoint. Otherwise they gave no numbers (no hazard ratio, no p-value, no effect size). We will have to wait for an upcoming medical meeting and everyone is hoping it’s going to be ESMO in late October.

Moderna management’s bar for the trial was a 20% risk reduction. The bullish case wanted 35% to 40%. Nobody outside the data monitoring committee knows which happened, and the stock nearly tripled anyway.

The market reaction tells me that people all around the world are excited about mRNA cancer treatments and that they believe melanoma is just the beginning. For thirty years we tried to vaccinate people against cancer and it almost never worked. Hartaj Singh (The Biotech Capital Compass) and I got into why in a podcast we recorded yesterday. We also discussed how the FDA has never approved a drug like this before and why kidney cancer will be the real test of the therapy.

The other big story of the week is about Chinese biotechs not reporting patient deaths until exposed by reporters. Three patient deaths in Chinese investigator-initiated trials have surfaced over the last month or so. The most recent was at RiboX Therapeutics, disclosed 10 days after the FDA cleared RiboX’s US investigational new drug application based partly on the same Chinese dataset. One boy’s death went unreported for about twelve months.

This week the European Commission formally revoked Tavneos, and CSL put a number on the damage, estimating about $145 million of fiscal 2026 sales lost. The reason all comes back to endpoints that were changed after unblinding in the pivotal trial. For now, the drug is still available in the US. Capricor faces the same question from the opposite direction on Saturday, whether the FDA will accept a favorable sounding open label extension to salvage a failed Phase 3.

Keep reading for more interesting stories and stay tuned for two emails next week - a podcast on Moderna and This Week in Biotech 115.

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BIOTECH/PHARMA NEWS 🧬

🔹 INTerpath-001 trial enrolled 1,137 patients with completely removed stage 2B-4 melanoma, randomized 2:1 to intismeran autogene (mRNA-4157) plus Keytruda or Keytruda alone. It was announced on Aug 19 that at a pre-specified interim analysis, it met its primary endpoint of recurrence-free survival and its key secondary endpoint of distant metastasis-free survival, with no new safety signals. However, the hazard ratios will come at an upcoming medical meeting. Intismeran is mRNA encoding up to 34 neoantigens, built from each patient’s tumor sequence, dosed at 1 mg every three weeks for up to nine doses. It is the first positive Phase 3 for any individualized neoantigen therapy and the first for an mRNA cancer therapy. The phase 2 behind it (n=157) had shown a 44% relative reduction in recurrence or death. William Blair models $5.4B in peak melanoma sales split evenly between the partners. Nine trials are running in lung, bladder and kidney cancer, and how well this extends to bulkier tumors is still an open question. Adjuvant melanoma is the best possible test case because of several reasons, including high mutational burden and minimal residual disease.

🔹 A patient with an autoimmune disease died after receiving RiboX’s experimental circular RNA therapy in a Chinese investigator-initiated trial. On August 8 the same company announced FDA clearance of an investigational new drug application for RXIM002, a lipid nanoparticle-delivered CD19 chimeric antigen receptor therapy made inside the body, for immune thrombocytopenia. That release said the investigator-initiated dataset “demonstrating safety and early efficacy” supported the submission and won an accelerated dose titration scheme for the US Phase 1. Two weeks earlier, HuidaGene disclosed that a boy in its HG302 Duchenne muscular dystrophy trial had died of acute respiratory distress syndrome in August 2025, after the highest viral dose given up to that point. The company confirmed it about twelve months later, after reporters asked, and changed the trial’s public status five days beforehand. There was no independent data safety monitoring board, so nobody outside the investigators reviewed the escalation that killed him. A third case involving a girl went unreported for sixteen months. Investigator-initiated trials let Chinese hospitals start cell and gene therapy studies without central regulatory sign off, which is exactly the mechanism producing the speed advantage Western pharma has been buying into for the last two years.

🔹 Trump nominated Heidi Overton as FDA Commissioner on August 19. She trained in general surgery at Johns Hopkins and holds a doctorate in clinical investigation, but her recent career has been in policy. She was chief policy officer at the America First Policy Institute, then deputy director of the White House Domestic Policy Council. She has no drug regulatory experience and has written critically of vaccine requirements and abortion medications. The agency has had no permanent leader since Marty Makary resigned in May. RBC’s Brian Abrahams called her impact on new drug review flexibility uncertain. What sponsors should probably assume is that review policy now gets set at the Department of Health and Human Services and the White House rather than at the FDA itself.

🔹 The FDA approved Regeneron’s garetosmab, branded Pasatru, on Aug 20 for fibrodysplasia ossificans progressiva, a disease affecting roughly 1 in 1M people in which muscle and connective tissue turn to bone. The activin A antibody cut new abnormal bone formation by 90% or more versus placebo over one year in Phase 3. Dosing of 3 to 10 mg/kg puts annual cost between $693k and $2.1M, averaging about $1.4M. Regeneron had paused development after several trial deaths before concluding the drug was unlikely responsible. A day earlier, Ultragenyx won accelerated approval for Genglycos, its first approved gene therapy, in glycogen storage disease type Ia for patients aged 8+. The approval endpoint was reduction in cornstarch intake, the crude but life-defining intervention these patients use to avoid blood sugar crashes. Price is $2.7M, with ten years of monitoring required. Analysts model peak sales of $362M. Ultragenyx also plans to sell its priority review voucher, and comparable ones went for $180-200M this year, so the voucher is worth roughly half the drug’s annual peak sales in a single transaction.

🔹 The European Commission adopted the decision revoking Tavneos’s marketing authorization across the EU on Aug 6, after a June 26 committee found that a positive benefit risk balance could no longer be established. This means roughly $145M of fiscal 2026 Tavneos revenue at risk, and CSL Vifor's total revenue is expected to fall about 25%, partly from losing Tavneos and partly from generic competition in their iron drug business. The reason is that primary endpoints in 9 patients in the registrational ANCA-associated vasculitis trial were altered after database lock and unblinding, without the knowledge of two academic authors. That produced the first NEJM retraction of a study supporting a marketed approval. Tavneos remains available in the US while Amgen contests a withdrawal proposal.

🔹 argenx’s Alkivia tested subcutaneous Vyvgart Hytrulo in immune-mediated necrotizing myopathy and dermatomyositis. In the combined population, mean Total improvement score at week 52 was 47.95 on drug versus 32.56 on placebo, a 15.4-point difference that was statistically significant and clinically meaningful. Separation began at week 4 and held through a full year, including through steroid tapering. The necrotizing myopathy cohort hit its endpoint on its own, the first Phase 3 to show significant disease-activity improvement in a subtype with no approved therapy, roughly 20k patients. Dermatomyositis moved the same direction without reaching significance. That split is interesting. FDA reviewers will have to decide whether a combined population win with one non-significant component is enough to support a broad myositis label. Vyvgart did about $2.9B in the first half of 2026 across generalized myasthenia gravis and chronic inflammatory demyelinating polyneuropathy. Shares rose more than 13%. The neonatal Fc receptor mechanism keeps working in new antibody-mediated diseases, and that’s really the durable thesis for the whole franchise.

🔹 Amylyx’s GLP-1 receptor antagonist avexitide cut serious to severe hypoglycemic events by 55% versus placebo in Phase 3, with most adverse events mild or moderate. Filing is planned before the end of 2026. There’s no approved treatment for post-bariatric hypoglycemia, a condition affecting one tenth to one third of bariatric surgery patients, a denominator that grows every year the GLP-1 era pushes more people through surgery. The drug blocks the same receptor the entire obesity industry is trying to activate, and works because excess GLP-1 signaling after gastric bypass drives insulin overshoot. Amylyx bought it for $35M out of Eiger’s 2024 bankruptcy, two years after withdrawing Relyvrio when its ALS confirmatory trial failed. Shares rose 14% after hours. Distressed biotech assets keep clearing at a fraction of what the same clinical data would cost in a competitive process.

🔹 Capricor is trying to avoid an FDA rejection on August 22. Its cardiosphere-derived cell therapy for Duchenne muscular dystrophy cardiomyopathy failed the Phase 3 HOPE-3 trial, and an advisory committee voted 9-3 in July that the data didn't show substantial evidence the drug works. To salvage the approval, Capricor is now submitting open label extension results from that failed trial. Shares fell 11% on Thursday. An open label extension of a trial that missed is one of the weakest forms of confirmatory evidence available. Everyone knows who got what, and the comparison runs against external controls. Two weeks ago Replimune proved an unfavorable process can still end in approval. Capricor is the same question in reverse, whether a favorable sounding post-hoc dataset can rescue a negative panel vote. If it can, advisory committee votes lose more of what little forecasting value they still have.

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Have a great rest of your week and thanks for reading Biotech Blueprint!

DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Front cover image source: Getty Images-SOPA Images/LightRocket

Treat yourself: biotech edition

The next leap in advanced therapies moves the production of medicines into the cell. What could that mean for patients?

Find out now

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, please get in touch.

📩 For consulting inquiries, please email me.

👥 If you haven’t already, connect with me on LinkedIn.

🛒 And make sure to check out our newly launched MERCH STORE.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Last week, I reported on Replimune’s Tudriqev getting accelerated approval by the FDA, four days past the deadline and eight days after an advisory committee voted 10-3 in its favor. Tudriqev is given to patients with advanced melanoma along with nivolumab. This week the label was made public and it lists efficacy at a 24.2% objective response rate in 91 patients. However, Replimune had been quoting 33.6% for two years, and the 32.9 month median overall survival that convinced the FDA advisory panel isn’t on the label at all. The number discrepancy comes from the FDA narrowing the efficacy population in the label to only include patients who had at least one tumor lesion that was never injected. That is because Tudriqev is injected directly into tumors, and you can’t tell if the drug is actually working throughout the body unless you can see uninjected tumors shrink too. This was a concern initially raised by the FDA in July briefing documents. So the FDA approved the drug but built its scientific criticism into the label by restricting which patients count for the efficacy claim.

Two more stories that remind us that regulatory approval isn’t the finish line for a drug. Prader-Willi syndrome patient organizations flagged 7 deaths and more than 100 serious adverse events for Neurocrine’s Vykat XR. Vykat XR is a drug that helps with hyperphagia (extreme, unsatisfied hunger and constant thoughts about food) in Prader-Willi patients and was purchased for $2.9 billion from Soleno Therapeutics in April 2026. The groups called for tighter patient selection and monitoring. Also, EU regulators published the assessment behind their June recommendation to pull Amgen’s Tavneos. Turns out the pivotal study “breached good clinical practice guidelines,” and the New England Journal of Medicine retracted the paper on June 29. This is the journal’s first ever retraction of a registrational study that supports an approval. So I dug a bit into the specific reason and it seems that the drug application relied on manipulated data for 9 patients that were changed after the trial was unblinded. The FDA has its own withdrawal proposal pending, which Amgen is contesting.

Lastly, on the policy side, two important things happened this week. Donald Trump signed a new executive order to yet again change the childhood vaccine schedule, however it will likely get tied up in court and won’t survive legal challenges. Merck is the only manufacturer of the only MMR vaccine in the US and has said splitting the shot into three is impractical and would almost certainly require new clinical studies. This executive order does not follow any new science or discoveries.

Secondly, the FDA is proposing that companies will get discounts if they run their phase 1 trials in the US or keep their manufacturing here. Once fees like this get written into law, they stick around, unlike executive orders or tariffs that can be reversed by a new administration. If this proposal passes, it might strengthen US biotech capacity in the long run, but it could also raise drug development costs and slow down how quickly new medicines reach patients because some of the fastest and cheapest infrastructure right now is outside the US.

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BIOTECH/PHARMA NEWS 🧬

🔹 Replimmune’s Tudriqev is a genetically modified herpes simplex type 1 virus injected directly into tumors, including deep and visceral lesions under imaging guidance, and given with nivolumab in unresectable advanced cutaneous melanoma that progressed on a regimen blocking PD-1. It’s the first accelerated approval built on a single arm study that FDA reviewers had twice rejected (July 2025 and April 2026). In the 91 patient efficacy-evaluable group, 80% of whom had stage 4 disease and 54% of whom lacked the PD-L1 protein on their tumors, the response rate was 24.2% with a median duration of 14.1 months. Serious adverse reactions occurred in 35% of the 140 patients treated and 2.9% discontinued. List price is about $450k per course, with launch expected within roughly two months. The confirmatory trial, IGNYTE-3, is about 1/3 enrolled and reads out overall survival in 2030, which means four years of commercial revenue will come before the data that justifies it. Analysts model $600M-$1B in peak US sales if it lands. A three year regulatory fight ended in a smaller win than the one Replimune was arguing for.

🔹 The Gold Standard Childhood Vaccine Recommendations executive order, signed August 10, cuts universally recommended childhood shots from 17 to 11, directs that the MMR vaccine be split into three separate shots once domestically available, requires that childhood vaccines be given at separate appointments, moves COVID-19 and influenza vaccination to shared clinical decision making for people who are not high risk, gives the Department of Health and Human Services 90 days to produce an adjusted schedule, and directs the Attorney General to challenge state religious and medical exemption laws. No new evidence accompanied it. Merck makes the only MMR vaccine sold in the US., and the company have said splitting it is impractical. Standalone mumps and rubella products would need new manufacturing lines and new clinical work, for a market the order itself would shrink. Senator Bill Cassidy, who chairs the Senate Health Committee, said Trump lacks the expertise to make the changes. The WHO called the order misguided, and the UK regulator reaffirmed its own schedule on Aug. 12. The direct commercial hit to drugmakers is modest. What is more concerning is that this sets a precedent for setting the childhood immunization schedule by presidential order instead of through the standard advisory committee process.

🔹 The FDA published commitment letters for the next reauthorizations of the Prescription Drug User Fee Act (PDUFA VIII) and the Generic Drug User Fee Amendments (GDUFA IV), covering 2028 through 2032. Included are what the agency calls America First provisions, which are cheaper application fees for sponsors running Phase 1 trials in the US, small business fee waivers only available to US applicants, onshoring incentives on the generic drug side, faster reviews for certain applications, and some new meeting types. Past user fee deals were about paying for faster reviews. This one uses fees to influence where the science actually gets done. The letters still need agency ratification, clearance from HHS and the White House budget office, public comment, and Congress, so terms can change. But once fees like this are placed into statute, they tend to outlast the administration that wrote them, unlike an executive order or a tariff. This lands on the same drug companies that spent 2026 fighting over Section 232 exemptions and China licensing deals. If you're picking a site for your next Phase 1 trial, your finance team is going to have to weigh this in.

🔹 Jazz agreed on August 10 to buy Actio Biosciences for $820M in cash plus up to $500M in regulatory and sales milestones, closing by Q4. The asset is ABS-1230, a first in class oral inhibitor of the KCNT1 ion channel, for a genetic developmental and epileptic encephalopathy that affects roughly 2500 people in the US and has no approved treatment. Jazz also takes a minority stake in a spun out rare neurology company holding ABS-0871. That $820M works out to about $330k per US patient with no clinical data yet in hand, on top of an epilepsy franchise Jazz already runs through Epidiolex. This is Jazz’s second deal of the year after the AbCellera T cell engager alliance in June. Mid cap acquirers keep going after rare disease drugs they can sell through their existing sales teams, rather than platforms they would have to build up separately.

🔹 Three Prader-Willi syndrome organizations issued a joint statement on August 11 flagging 7 deaths and more than 100 serious adverse events reported to the FDA’s adverse event system through July 31, mostly involving edema, respiratory, and cardiac problems. The groups were careful to note the reports don’t establish causation, and spontaneous reporting in a population with high baseline respiratory and cardiac mortality is hard to interpret. But they still called for tighter patient selection and monitoring. Neurocrine stands by the drug. Vykat XR is the first therapy approved to reduce hyperphagia in Prader-Willi syndrome, and Neurocrine paid $2.9B to Soleno in April to get it. Similar story to Celcuity and MapLight last month. FDA approval is one thing, but holding up in the real world is another test.

🔹 The bankrupt gene-editing pioneer Sangamo sold its assets for up to about $264M combined. PTC Therapeutics won ST-920 (isaralgagene civaparvovec), a single infusion gene therapy for Fabry disease, for $111M upfront plus $80M on accelerated approval and $20M on full approval. Lilly took the zinc-finger platform programs for $50M in cash. What’s interesting is how much the final price jumped from the opening bid. Astellas had originally offered $25M upfront and $25M in milestones for the Fabry asset. The competitive auction pushed the final price more than fourfold in a matter of weeks. PTC finishes the rolling submission in Q4 and could launch in 2027 into a Fabry market above $2B. So yes, gene therapy companies are going bankrupt, but their late stage assets are still generating real prices at auction.

🔹 A single 100 mcg oral dose of LSD from Definium Therapeutics cut Hamilton Anxiety Rating Scale scores by 11.6 points from baseline at week 12 versus 6.2 on placebo, a placebo-adjusted difference of 5.4 points at p<0.0001. Separation appeared by day 2 and held. There were no new safety signals and no suicidality signal. 92% of participants cleared the end of session checklist by eight hours, averaging 6.4 hours. The company, which was MindMed until January, now has positive Phase 3 data in both major depression (June) and anxiety off one molecule, and holds breakthrough therapy designation here. Analysts model $1.5-2B in depression alone and up to $5B across three indications. The stock rose 15%. The catch is the same catch as every psychedelic trial. A 5.4 point separation is large for psychiatry, but everyone who received an active dose of LSD knew they took it. The next pivotal trial, Panorama, adds a 50 mcg arm specifically to test whether functional unblinding is doing the work. The September readout from that trial is what will really determine the label.

🔹 Zipalertinib from Taiho Oncology and Cullinan Therapeutics plus chemotherapy beat chemotherapy plus placebo on progression-free survival by enough to trigger early unblinding at a pre-planned interim look in first line EGFR exon 20 insertion lung cancer. The trial was powered to detect a 40% reduction in the risk of progression or death, so the effect cleared that bar. The hazard ratio and enrollment were not disclosed and the full data go to a future meeting. The context makes this story interesting. J&J’s Rybrevant, the incumbent in this genetically defined subset, is an infusion and did over $700M in 2025. AstraZeneca and Dizal’s Zegfrovy, which is oral, cut progression risk 35% as monotherapy. Zipalertinib is also oral, already under FDA review for second line use with a decision due Feb. 27, 2027, and now has front line data to support a label expansion. ArriVent’s firmonertinib reads out later this year. So four drugs are chasing a mutation that appears in only about 2% of non-small cell lung cancer, and the fight is about dosing format more than the underlying mechanism.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

The FDA approved three first-in-class drugs this week. Moderna’s mFluSiva is the first licensed influenza vaccine built on mRNA. Takeda’s Orzeyful (oveporexton) is the first orexin receptor 2 agonist, and the first drug that treats narcolepsy type 1 by restoring the signal patients have lost rather than just stimulating them around it. Both open new categories, not just single product approvals. And in Moderna’s case, the FDA had issued a refusal to file on this exact program only 18 months ago.

The FDA also granted accelerated approval to Replimune’s Tudriqev (vusolimogene oderparepvec-wtpg) on August 6, four days after the August 2 decision deadline and one week after its advisory committee voted 10-3 that the efficacy data are evaluable and clinically meaningful. This is Replimune’s third review cycle after rejections in July 2025 and April 2026.

The second story is obesity, and the race isn’t close anymore. Lilly booked $23B in the quarter, up 48% and raised full year guidance to $85B to $87B, driven by tirzepatide alone. Novo missed on the oral Wegovy line and, more damaging, disclosed that CagriSema failed to prove non-inferiority to tirzepatide on blood sugar in the head-to-head REIMAGINE 4 trial. That’s the second direct loss to Lilly’s molecule in six months, after CagriSema missed on weight in REDEFINE 4. Novo’s CEO spent the earnings call talking about small acquisitions to fill pipeline gaps, which usually means the company can’t fix things with its own pipeline.

Capital markets had a busy week too. Five biotechs went public and raised more than $1 billion combined, bringing 2026 to 17 IPOs and 12 that raised at least $250 million each. All of 2025 only produced 11. Meanwhile, the Financial Times mentioned a rumored $400 billion merger between AstraZeneca and Bristol Myers Squibb, which knocked about 9% off AstraZeneca’s stock before the whole story was denied by an insider. So investors are happy to pay premium prices for fresh science and clearly don’t want to pay for consolidation between two aging pipelines.

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🔹 The FDA approved Moderna’s mFluSiva on August 5 for seasonal influenza in adults 50 and older. Standard approval in the 50 to 64 group, accelerated approval in 65 and older contingent on a confirmatory trial running across two flu seasons. The pivotal data showed a 27% relative reduction in influenza-like illness compared with a standard dose flu shot in adults 50 and over, with no new safety signals. What matters here almost as much as the approval itself is the regulatory part of it. Moderna received a refuse-to-file decision on this exact program under Marty Makary and Vinay Prasad. Both are gone from the agency, a June advisory committee voted unanimously in favor, and the product is now approved in time for the 2026-2027 season. The commercial case rests on manufacturing speed. Conventional flu vaccines require a strain call months ahead of the season and a production run that can’t be revised, but an mRNA process can. If the confirmatory data hold in the 65+ population, strain match becomes the whole commercial argument against Sanofi, GSK, and CSL.

🔹 Takeda’s Orzeyful (oveporexton) was approved August 5 for narcolepsy type 1 in adults, the first medicine to target the biology of the disease directly. Narcolepsy type 1 is caused by loss of orexin-producing neurons, and existing therapy is stimulants and sodium oxybate, which manage symptoms without touching the deficit. Jefferies puts the annual price between $142k and $250k, and roughly $2B in peak sales at the low end. Launch waits on the Drug Enforcement Administration, which has up to 90 days to assign a control schedule. The phase 3 FirstLight and RadiantLight data behind the approval were clean. Mean sleep latency on the Maintenance of Wakefulness Test improved by 13.83 minutes at 1 mg and 17.2 mins at 2 mg against placebo, both at p<0.001. Weekly cataplexy rate fell more than 80% from baseline relative to placebo, with patients reporting four to five cataplexy free days a week at week 12 against none at entry. The interesting question is where the class goes, not the specific drug. Alkermes is running alixorexton across narcolepsy type 1, type 2, and idiopathic hypersomnia, explicitly to arrive with a broader label than Takeda’s. Lilly bought into the mechanism through the $6.3B Centessa acquisition. Eisai has its own candidate. Takeda gets first mover pricing in the smallest of the three indications, and the larger populations are still open and that’s where the class gets decided.

🔹 The FDA granted accelerated approval to Replimune's Tudriqev (vusolimogene oderparepvec-wtpg) on August 6 for advanced melanoma in patients who have progressed on anti-PD-1 therapy, in combination with nivolumab. Tudriqev is a genetically modified oncolytic viral therapy based on herpes simplex virus type 1, injected directly into tumors every two weeks for eight doses. In the pivotal single arm trial of 91 evaluated patients, 24% achieved an objective response with a median duration of 14.1 months. The approval landed four days after the August 2 decision deadline and one week after the Cellular, Tissue and Gene Therapies Advisory Committee voted 10-3 that the efficacy data are evaluable and clinically meaningful. This is Replimune's third review cycle. The FDA had previously rejected the application in July 2025 and April 2026, and briefing documents released two weeks before the panel meeting had called the trial "not interpretable" on the grounds that a single arm intratumoral injection study couldn't separate RP1's contribution from Opdivo's. The panel disagreed and the FDA, eventually, agreed with the panel. Two weeks produced a briefing document that took 30-40 % off the stock, a panel vote that doubled it, a deadline that passed, and finally an approval four days late.

🔹 Lilly reported $23.0B in Q2 revenue, up 48%, against a $20.6B consensus. Mounjaro rose 91% to $9.94B worldwide, US Zepbound rose 44% to $4.9B, non-GAAP earnings per share rose 33% to $8.38, and full year guidance moved to $85.0B to $87.0B from $82.0B to $85.0B. Foundayo, the oral GLP-1, brought home $98M in its first reported quarter against $104M expected, which nobody punished because expectations were already low. Novo’s oral Wegovy came in at DKK 3.2B, about $494M, versus DKK 3.6B expected, and the shares fell 6%. Novo did raise its own full year sales forecast, from a range of down 4% to down 12% to a narrower range of flat to down 6%. But the direction of the franchise isn’t really in question. Lilly is growing at 48% on an injectable that has now beaten Novo’s next generation combination twice head to head.

🔹 Novo Nordisk’s CagriSema was compared head-to-head against Lilly’s tirzepatide 15 mg in about 1,000 adults with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor, over 68 weeks. On weight, CagriSema was non-inferior at 15.2% versus 15.8%. On glycemic control, it wasn’t. HbA1c fell 1.9 percentage points versus 2.2 for tirzepatide, missing the non-inferiority margin. A 1.9-point HbA1c reduction is a strong result in absolute terms and would have been a big headline against placebo three years ago. But Novo chose the comparator, chose the dose, and lost on the primary endpoint. Combined with REDEFINE 4, where CagriSema missed non-inferiority on weight in obesity, the amylin+semaglutide combination has now been tested directly against Lilly’s molecule twice and come up short on both axes that matter commercially. So CagriSema’s launch case has to be built on tolerability or price rather than efficacy.

🔹 The Financial Times reported on August 3 that AstraZeneca and Bristol Myers Squibb had held early talks about combining, which would have created a roughly $400B company and one of the largest deals in the industry’s history. AstraZeneca’s shares fell as much as 7-9%. On Aug. 5, a senior source told Reuters there never was a deal and there are no discussions. The London listing recovered about 3%. Whether talks actually happened is unresolvable from the outside. The shareholder reaction, however, is not ambiguous. AstraZeneca has a functioning oncology and cardiometabolic pipeline, and the mere suggestion that it would spend its equity on Bristol Myers, whose Revlimid and Eliquis patent cliffs are the reason it would want the deal, cost it nearly a tenth of its market value in a day.

🔹 Braveheart Bio raised $382.5M, pricing 21.25M shares at $18 for BHB-1893, a cardiac myosin inhibitor licensed from Hengrui Pharma for hypertrophic cardiomyopathy and aimed at Bristol Myers’ Camzyos. Hengrui is running Phase 3 in the obstructive form in China. Braveheart plans global trials in both obstructive and non-obstructive disease starting late 2026. Attovia raised $289M at $17 for a $767M valuation on ATTO-1310, an antibody against interleukin-31, the itch cytokine, in Phase 1 for chronic pruritus and severe eczema. Braveheart is the 17th drugmaker to go public in 2026 and Attovia the 12th to raise at least $250M, against 11 offerings in all of 2025. Median deal size this year is around $300M. Braveheart is also the second listing of 2026 built on a Hengrui-licensed molecule, which means the China licensing arbitrage model has now moved from private deal rooms into the public markets.

🔹 Tarsus Pharmaceuticals is acquiring Alkeus for about $450M upfront, $270M cash and $180M stock, plus up to $350M in milestones and a low to mid single digit revenue share. The asset is gildeuretinol (ALK-001), a daily oral in Phase 3 for Stargardt disease, an inherited retinal degeneration with no approved treatment. The mechanism is deuteration of vitamin A to slow the dimerization that produces toxic retinal byproducts, and the drug has been studied in more than 400 individuals. Tarsus is spending the balance sheet from its marketed eye care product on a late stage rare disease program in an indication where any approval is the first.

🔹 Intellia disclosed that an analysis of more than 600 patient samples across the nex-z program identified a specific human leukocyte antigen allele associated with the largest liver transaminase elevations seen in the trials. The company will return HLA genotyping results to investigators and to patients already enrolled or entering screening in the phase 3 studies, and is discussing the finding with regulators. Enrollment, which had been paused after a grade 4 transaminase and bilirubin elevation in a patient who later died, has been restarted. MAGNITUDE-2 in hereditary ATTR with polyneuropathy should complete enrollment in the second half of 2026. This is arguably the most useful thing to happen to in vivo gene editing safety this year. The standing problem with the field is that a one time, irreversible edit leaves no way to de-risk an individual patient after the fact. An inherited immune genetic marker that flags who’s likely to mount the hepatic response converts an unpredictable platform risk into a screening step, if regulators accept it.

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DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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A platform for personalized medicine

Genomic medicine off the shelf: LNPs as a platform for interchangeable, personalized molecules.

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🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, get in touch.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Earnings week showed a clear contrast in how big pharma is spending. Sanofi wrote off about €1 billion (€952M of it on amlitelimab, an OX40 ligand antibody) and killed three immunology programs. GSK announced £1.9 billion in annual cuts and is closing its Stevenage research site. Takeda, Regeneron and Bristol Myers all trimmed programs in the same 48 hours. But at the same time, argenx paid $2.2 billion (an 86% premium) for Forte Biosciences and its first in class CD122 antibody, and Johnson & Johnson committed $785 million upfront on Sail Biomedicines, a preclinical in vivo CAR-T platform, with an option to buy the whole company for another $2.58 billion. Big pharma isn't abandoning immunology but it seems to be abandoning conventional antibody immunology. What they will pay up for right now is mechanism novelty with a clinical signal, or a delivery technology that changes the economics of an approved modality.

The other big thread was regulatory. The FDA’s advisory committees are back, and they’re not being gentle. A panel voted 9-3 that Capricor had not shown enough evidence that deramiocel works in Duchenne cardiomyopathy, with reviewers describing the cardiac benefit as a mirage produced by revising the statistical analysis plan. A day earlier, briefing documents called Replimune’s melanoma trial “not interpretable” and the stock lost 30 to 40% before the panel even met. Both companies are on their second or third try at the same approval. The convenient story since Marty Makary left has been that this FDA is looser. What’s actually happening is that contested cases are being sent to public panels rather than handled inside the agency, which puts the risk on shareholders and makes the briefing document itself the tradable event. The acting chair of the FDA’s oncology panel also resigned this week, leaving a thin bench thinner.

Last thing worth noting is that incretins keep finding new organs to work on. Altimmune’s pemvidutide cut heavy drinking days by 1.45 more per week than placebo in alcohol use disorder, every key secondary hit, and a biomarker of alcohol intake was down at p<0.0001. Small trial, about 100 patients over 24 weeks, but alcohol use disorder has three approved drugs that basically nobody takes, and this is the first controlled mid stage trial of a glucagon/GLP-1 dual agonist to read out in the indication. Still early but it keeps alive the idea that the metabolic platform reaches into addiction.

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BIOTECH/PHARMA NEWS 🧬

🔹 argenx is acquiring Forte Biosciences for about $2.2B, $77 per share in cash via tender offer, roughly an 86% premium to Forte’s volume weighted average price since it reported positive phase 1b vitiligo data on July 9. The asset is FB102, a first-in-class antibody against CD122, the shared receptor subunit that gates interleukin-2 and interleukin-15 signalling in pathogenic T cells and natural killer cells. Forte has clinical proof of concept in two very different diseases, vitiligo and celiac, which is what argenx is paying the premium for. The company is pitching FB102 as a pipeline in a product, with alopecia areata and other autoimmune indications behind it. Strategically this is argenx buying a second engine. Vyvgart (efgartigimod) is a neonatal Fc receptor blocker that clears pathogenic antibodies, and it is carrying essentially the whole company. CD122 attacks upstream cellular drivers instead, and it’s a mechanism argenx doesn’t otherwise run. Three weeks from a Phase 1b readout to a signed $2.2B tender offer is the fastest data to deal conversion of the year.

🔹 Johnson & Johnson is paying $785M upfront, including a $465M equity investment, for an exclusive option to acquire Sail Biomedicines outright for $2.58B. Sail was formed from the 2023 merger of Flagship Pioneering’s Senda Biosciences and Laronde, and combines circular “endless RNA” payloads with programmable nanoparticles to reprogram T cells inside the patient rather than in a manufacturing suite. The lead program, SAIL-0839, is still preclinical and its target disease has not been disclosed. J&J is buying the manufacturing thesis, not a molecule. Conventional CAR-T requires apheresis, ex vivo engineering and lymphodepleting chemotherapy, which is tolerable in relapsed blood cancer and unworkable in lupus or myositis. In vivo delivery is the only route to autoimmune scale volumes. That logic is now consensus, which is why at least six in vivo CAR-T developers have been bought since early 2025, Eli Lilly taking Kelonia and Bristol Myers taking Orbital among them.

🔹 The FDA’s Cellular, Tissue and Gene Therapies committee voted 9-3 on July 29 that Capricor had not demonstrated substantial evidence of effectiveness for deramiocel in Duchenne-related cardiomyopathy. Agency reviewers argued the benefit was “essentially a mirage aided by switching up a statistical analysis plan” and that the changes “lack a scientific basis.” The arithmetic supports the charge. Under a revised statistical model, the left ventricular ejection fraction effect moved from 2.4 percentage points at p=0.04 to 1.8 points at p=0.09. Panelists called the findings fragile. The decision date is August 22, following a complete response letter in July 2025. Two days earlier the same dynamic hit Replimune, whose shares fell roughly 30 to 40 percent when reviewers called the single-arm IGNYTE trial for RP1 plus nivolumab “not interpretable,” on the grounds that an intratumoral injection study can’t separate a systemic anti-cancer effect from a local one. RP1 posted a 33.6% objective response rate and a 24.8 month median duration of response in anti-PD-1 failed melanoma, and has already been rejected twice, in July 2025 and April 2026. Its panel met July 30 on a single question, whether the results are evaluable and clinically meaningful, with a decision due August 2.

🔹 GSK is taking out about £1.9B ($2.5B) in annual costs over three years, closing its Stevenage research site and building a new global research centre in Cambridge, UK. The forcing function is dolutegravir, the backbone of a HIV franchise that generated more than $5B last year and loses patent protection between 2028 and 2030. Chief executive Luke Miels is holding a £40B 2031 sales target with 62 drugs in the clinic and 19 in late stage testing, funded partly by redeploying the savings into late stage programs and partly by the acquisitions of Nuvalent (about $11B), Rapt Therapeutics ($2.2B), Boston Pharmaceuticals ($1.2B) and 35Pharma. Job numbers were not disclosed. Shares rose about 4%, with Jefferies noting the cut was roughly double what it expected. GSK also expanded its artificial intelligence partnership with Relation Therapeutics to as much as $110M. Cutting the base and buying the pipeline is the standard patent-cliff playbook. The tell is that the R&D estate itself is being consolidated, not just headcount.

🔹 Sanofi recorded €1B in impairment charges in the second quarter, €952M of it on amlitelimab, and discontinued amlitelimab, itepekimab and balinatunfib. Itepekimab is the Regeneron-partnered interleukin-33 antibody that failed one of a pair of Phase 3 trials in chronic obstructive pulmonary disease. The commercial business is not the problem. Sales grew 17.8% in the quarter, Dupixent grew 37.6%, and full year guidance was upgraded to about 10% growth at constant exchange rates. Three months into the job, chief executive Belén Garijo is describing the plan as an R&D cleanup plus more M&A plus a China push, which is the same sequence GSK and Biogen are running. The uncomfortable read for the sector is that the assets being cut are late stage immunology antibodies at a company that owns the category’s biggest drug. If Sanofi can’t make a second wave cytokine antibody pay behind Dupixent, the bar for everyone else’s is higher than the consensus models assume.

🔹 Altimmune’s RECLAIM trial randomised about 100 patients 1:1 to 2.4 mg of pemvidutide, a glucagon/GLP-1 dual agonist, or placebo once weekly for 24 weeks in adults with alcohol use disorder. Heavy drinking days fell by 4.2 per week from baseline on drug versus 2.75 on placebo, a placebo-adjusted difference of 1.45 days at p=0.0014. Every key secondary hit: patients reaching zero heavy drinking days (p=0.0066), percentage of abstinent days (p=0.0075), and phosphatidylethanol (p<0.0001), a blood biomarker of alcohol intake that is much harder to fake than a drinking diary. Placebo-adjusted weight loss was 9.1% at 24 weeks (p<0.0001). Tolerability was described as generally favourable. The biomarker result matters more than the diary result, because self reported drinking in a trial where patients know they are being watched needs to be taken with a grain of salt. Alcohol use disorder affects tens of millions of American adults and has three approved medicines that almost nobody takes. A Phase 3 in this indication would be the first serious test of whether incretin biology reaches reward pathways rather than just appetite.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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Solving the drug discovery crisis

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Another update in the GLP-1 world this week. For two years the only question that moved stocks was how much weight a drug takes off. Lilly’s retatrutide, the most powerful weight loss molecule in development, answered that question again with two more Phase 3 wins, and the market barely cared. What the market cared about was the two harder questions that came with the data. Does the weight loss protect the heart, and did the drug hold its own prior ceiling? Both answers were underwhelming. Peak weight loss came in around 21% to 23%, below the 28.3% retatrutide posted in TRIUMPH-1, and the trial specifically run in people with cardiovascular disease couldn’t show the drug reduced heart attacks, strokes, or cardiovascular death. The regulatory filing slipped to Q1 2027. Efficacy has a visible ceiling now, and the next front is outcomes data.

That front is also a courtroom. In the same week retatrutide disappointed, Novo Nordisk sued Lilly over what it calls “maliciously and deceptively false” advertising comparing the highest doses of the two companies’ drugs. The two players who own the obesity market aren’t just competing on weight percentages and payer coverage anymore. They’re competing on what each is allowed to say about the other. When rivals move from trial design to trademark law, it usually means the clinical differentiation has narrowed enough that how you talk about the drug matters.

M&A this week kept validating on the science while raising the price question. GSK’s $10.6 billion purchase of Nuvalent, closed only a week earlier, already produced an FDA approval two months ahead of schedule for Jideytro in ROS1-positive lung cancer, GSK’s first lung cancer drug ever. In the same news cycle, the post-mortem on Vertex’s $10 billion Crinetics deal revealed that Vertex was the sole bidder and paid the second-highest premium of biotech’s banner M&A year. It was essentially bidding against itself.

Two policy stories are worth mentioning. President Trump threatened tariffs of up to 200% on generic drugs not manufactured in the United States, the first time copycat medicines specifically have been targeted, which matters far more to drug supply than the branded pharma levies did. Sartorius became the first life science company to quantify the other side of the tariff mess, cutting revenue by 26 million euros to refund customers after the Supreme Court blocked some of the earlier levies. Meanwhile Merck’s Rob Davis warned Congress that cutting off China dealmaking would cost the US its status as the world’s biotech leader. So now the biggest pharma CEOs are publicly arguing against restrictions on China deals while their own companies keep signing them.

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BIOTECH/PHARMA NEWS 🧬

🔹 Novo Nordisk took Lilly to court over advertising that compares the highest doses of Zepbound and Wegovy and claims Lilly’s products are broadly superior. Novo calls the campaign “maliciously and deceptively false” and filed after a cease and desist request went nowhere. Lilly countered that its campaign is “truthful.” The lawsuit is the clearest sign yet that better clinical data is not enough to win share anymore in obesity. Lilly’s tirzepatide has generally shown deeper weight loss than semaglutide in head to head reads, which is exactly why Novo is contesting how that comparison is framed to prescribers and patients. As both franchises reach tens of $billions in revenue and the pipeline gap narrows, how each company markets against the other is now worth taking to court. Worth watching whether a court is willing to police direct drug versus drug advertising claims, which would set a precedent for every crowded category behind obesity.

🔹 The FDA approved GSK’s Jideytro (zidesamtinib) for previously treated ROS1-positive metastatic non-small cell lung cancer, GSK’s first lung cancer approval and the payoff on its largest acquisition in eight years. The clearance landed ahead of a September 18 decision date, helped by breakthrough therapy and orphan drug designations. ROS1 rearrangements appear in roughly 2% of non-small cell lung cancer, a small but well defined niche where selectivity, resistance-mutation coverage, and control of brain metastases decide the winner against existing drugs. GSK essentially bought a derisked, nearly approval asset and got revenue faster than its own model assumed, with a second Nuvalent drug, neladalkib, still under FDA review. This is the cleaner half of the M&A validation story this week. Pay up for a specific molecule near the finish line and the timeline can surprise to the upside.

🔹 The regulatory filing behind Vertex’s $10B Crinetics acquisition showed Vertex was the only company at the table and still paid the second highest premium in a year full of premiums. Analysts expect the disclosure to reignite the concern that Vertex overpaid for its largest ever deal, an endocrine pivot beyond cystic fibrosis anchored by Palsonify in acromegaly and atumelnant in late stage adrenal disease. The detail that matters is the absence of a competing bid. A 100%+ premium is easier to defend when two strategics are fighting over an asset, but it is much harder when the acquirer set the price against no one. The clinical thesis doesn’t change here, since Crinetics has a differentiated oral endocrine portfolio, but it sharpens the question of what disciplined dealmaking looks like when capital is cheap and the IPO window is wide open.

🔹Two policy stories worth mentioning this week. President Trump pledged tariffs of up to 200% on generic drugs not made in the United States, the first time generics specifically have been targeted. That is a bigger deal than the branded pharma tariffs that had limited revenue impact, because generics are where supply is thinnest, margins are lowest, and shortages are already common. A punitive import levy on copycat medicines could disrupt the drugs most Americans actually take. Separately, Sartorius cut its revenue guidance by 26M euros to refund customers for tariff surcharges it had passed on earlier in the year, after the Supreme Court blocked some of those tariffs. It is the first company to publicly quantify the financial cost of the on-again, off-again tariff policy. And Merck CEO Rob Davis warned Congress that restricting US-China dealmaking would cost the country its biotech leadership position, given how many pipeline drugs now come from Chinese licensing. Trade and China policy are quickly becoming things pharma companies have to actively plan around.

🔹 Repligen agreed to acquire cell processing supplier BioLife Solutions for roughly $1.5B, about 36% of it in stock. The interesting angle is what Repligen is buying. BioLife supplies reagents, media, and cold chain equipment to cell and gene therapy developers. So this is one tools company buying another tools company, which is essentially a bet that cell and gene therapy manufacturing volume keeps growing overall, regardless of which specific drugs succeed. BeOne (formerly BeiGene) also announced a $300M domestic manufacturing expansion the same day. Both deals show that some of the biggest checks in biotech right now are going to infrastructure.

🔹 Lilly’s retatrutide, a triple agonist that hits the GLP-1, GIP, and glucagon receptors, met the primary endpoints of both Phase 3 trials but on terms that cooled the enthusiasm. In TRIUMPH-2, the type 2 diabetes cohort, top-dose patients lost about 21% of body weight at 80 weeks. In TRIUMPH-3, run in people with established cardiovascular disease, weight loss reached roughly 22.6% to 23%. Both are strong absolute numbers and both fall short of the 28.3% retatrutide posted in TRIUMPH-1 in people without diabetes, which is the expected pattern since diabetes and cardiovascular populations typically lose less. The disappointment is the heart data. TRIUMPH-3 recorded 27 major adverse cardiovascular events on retatrutide versus 23 on placebo for the three point measure of cardiovascular death, heart attack, and stroke. So the drug didn’t demonstrate it lowers cardiovascular risk. A broader five point measure that adds all cause death and heart failure numerically favored the drug, but the sample is too small and the follow up too short to draw a clean conclusion. Lilly now plans to file with the FDA in Q1 2027, delayed for manufacturing and quality data. Retatrutide will very likely be the most powerful weight- oss drug on the market, but the industry’s next differentiator, proving the weight loss translates into fewer heart attacks and strokes, remains unclaimed. Novo’s semaglutide already carries a cardiovascular benefit label, which is precisely the ground the two companies are now fighting over in court.

🔹 Arrowhead’s RNA-interference drug plozasiran hit strong numbers in two late-stage trials in severe hypertriglyceridemia, a much larger patient population than the ultra rare familial chylomicronemia syndrome where the drug is first headed. Plozasiran cut triglycerides by a median 79% in one trial and 81% in the other at one year, versus roughly 27% in the placebo arms. A pooled analysis showed a 78% reduction in acute pancreatitis events, which is the complication that kills people with severe hypertriglyceridemia. Safety was clean, with no meaningful liver enzyme or platelet changes. The biggest practical advantage is dosing. Plozasiran is a subcutaneous injection once every three months. Ionis’s Tryngolza requires monthly injections. Arrowhead plans to file to add severe hypertriglyceridemia to the Redemplo label before the end of 2026.

🔹 Summit released longer follow up on its PD-1/VEGF bispecific ivonescimab in an effort to answer the skeptics who have questioned whether the striking Asian trial results hold up in Western patients. The updated cut of the global Phase 3 offered two year survival data with a favorable read, but the context investors most want is still missing: the direct, adequately powered comparison of benefit between Asian and Western populations. The stock has traded on this exact uncertainty all year, including a pulled secondary offering in June. Ivonescimab remains the most important test of whether Western regulators and prescribers will accept a China-originated oncology drug on data largely generated abroad, and this readout narrows but doesn’t close the gap. It keeps the idea alive that the bispecific works across populations without yet proving it.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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Designing the therapeutic effect

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

The most important approval of the week is a pill developed by Merck. The company won US FDA clearance for Lipfendra (enlicitide), the first once daily oral drug that blocks PCSK9, the protein that clears the liver’s LDL receptors. For a decade, potent PCSK9 blockade meant an injection every two to four weeks, either Amgen’s Repatha or Novartis’s twice yearly Leqvio. Merck’s version matches injectable-grade LDL cholesterol reduction in a swallowable tablet at $315 a month. This is the same mechanism delivered through a format patients actually take. The pattern repeats down the page this week. Another company reported that an oral pill grew hair in women where the standard is a topical foam, and the obesity field has spent a year migrating from injections to oral GLP1s. Convenience, not novelty, is what companies are competing on right now.

There’s an irony inside the Merck approval. It cleared in one to two months because of the priority voucher program built by former FDA Commissioner Marty Makary, whose voucher Merck collected in December. Yet in the same week, the FDA’s acting leadership publicly walked back this practice, declaring that two of his medical journal articles never constituted actual agency policy. So the agency is dismantling his methods while cashing his vouchers. Makary the person is gone, but Makary’s machinery is still approving blockbusters.

The other big theme this week is capital, and how much of it is moving. Eli Lilly bought its way into psychedelics with a $2.8 billion upfront deal for AtaiBeckley, its eleventh acquisition of 2026. AI drug discovery startup Chai Discovery raised $400 million at a $3.8 billion valuation, and radiopharma maker AdvanCell pulled in $315 million, while at least four biotechs filed to go public in two weeks. The obesity cash machine is funding an acquisition spree, the IPO window is wide open, and China-sourced assets keep flowing to Western buyers. The bear case on biotech financing that dominated 2024 and 2025 seems to have disappeared.

There's one story from this week that cuts against the optimism, though. Celcuity won FDA approval for a genuinely differentiated breast cancer drug and the stock fell almost 20%. This is a reminder that FDA approval doesn’t automatically translate to a stock move up. If the label is narrower than expected, the launch is delayed, or the prescribing information shows worse safety than the trial data suggested, the stock can still fall. Small biotechs have to clear two bars and those are the FDA and whatever expectations investors had already priced in.

BIOTECH/PHARMA NEWS 🧬

🔹 Merck’s Lipfendra (enlicitide) became the first once-daily pill to inhibit PCSK9, approved to lower LDL cholesterol in adults with high cholesterol, including inherited heterozygous familial hypercholesterolemia. It’s a macrocyclic peptide, an unusually large molecule for an oral drug, engineered to survive the gut and block a target that injectable antibodies and RNA therapies had monopolized. The efficacy is the point. In the Phase 3 CORALreef Lipids trial, enlicitide cut LDL cholesterol by a placebo-adjusted 55.8% at 24 weeks and 61.5% at one year, with a 59% reduction in the familial hypercholesterolemia study and that’s injectable-class potency. At $315 for a 30 day supply, it undercuts branded injectables and prices near generic injectable PCSK9s ($500 to $600 a month), while offering the format advantage no injectable can match. RBC Capital Markets projects more than $5B in peak annual sales. Merck earned the fast review through the priority voucher it received in December, cutting the timeline to one to two months, and beat AstraZeneca’s competing oral candidate to market. Repatha ($3B in 2025) and Leqvio now face an oral competitor with equivalent LDL lowering, and the cardiovascular outcomes data Merck is still generating will decide whether pill convenience translates into franchise displacement.

🔹 Lilly agreed to buy AtaiBeckley for $6.75 per share, about $2.8B upfront, with a contingent value right of up to $2.50 per share pushing the total toward $3.8B. The lead asset is BPL-003, a mebufotenin analog (a molecular cousin of psilocybin) in late stage testing for treatment-resistant depression, where a single dose has produced rapid symptom reduction. This is the strongest signal yet that large pharma is done watching psychedelics from the sidelines. The commercial proof point is Johnson & Johnson’s ketamine-derived Spravato, which generated almost $1.1B in the first half of 2026, up 43% year over year, showing that a scheduled, clinic-administered psychiatric drug can scale commercially. For Lilly, this is deal number eleven of 2026, more than any peer, and it continues the pattern of using obesity cash flow to buy modality and indication breadth rather than adjacent metabolic assets. Compass Pathways, the longtime psychedelics company, now has a very well-funded competitor. The open question is regulatory and logistical. These therapies require monitored dosing sessions, and reimbursement plus clinic infrastructure, not efficacy, is the gating constraint.

🔹 The FDA approved Celcuity’s Revtorpyk (gedatolisib), a pan-PI3K/AKT/mTOR inhibitor, for second-line ER-positive, HER2-negative advanced breast cancer, in combination with fulvestrant and Ibrance (palbociclib) or with Ibrance alone. The differentiated angle is that the label covers patients without PIK3CA mutations, a segment competitors from Novartis and Roche have largely left alone while focusing on the mutant population. In VIKTORIA-1, the three drug regimen delivered median tumor control of 9.3 months versus 2 months for fulvestrant alone. The two drug regimen reached 7.3 months. Yet shares fell almost 20% on two disappointments buried in the fine print. The company signaled a later launch than its prior commentary implied (now late in Q3), and the prescribing information carried higher treatment discontinuation rates than the conference data had shown. This is the recurring lesson of 2026 small cap approvals. A genuinely useful drug in an underserved niche is not automatically a good stock day when the label and the launch timeline undershoot what investors had already paid for.

🔹 Two more Western-Chinese deals landed this week. AstraZeneca agreed to pay Shanghai-based Dizal $600M upfront, up to $1.5B total, for global rights to Zegfrovy, an already marketed lung cancer drug for EGFR exon 20 insertion mutations that did about $85M in 2025 sales. Buying a derisked, approved asset rather than a preclinical one is a notable escalation of the China sourcing model. Separately, Spero Therapeutics licensed most rights to Innovent’s anti-CD40L antibody IBI355 for immune diseases, with Innovent eligible for up to $1.1B. Meanwhile, the Biotech Investment National Security Act, the House bill that would subject US biotech deals with Chinese companies to national security review, is now stalled after unsettling the industry last month.

🔹There’s a lot of biotech financing happening right now. At least four biotechs filed to go public in two weeks, including Braveheart Bio, which is funding Phase 3 testing of a Hengrui-licensed cardiac myosin inhibitor aimed at Cytokinetics and BMS, and immunology and inflammation player Attovia. On the private side, AI structure prediction startup Chai Discovery raised $400M at a $3.8B valuation, the second-largest venture round tracked this year. Radiopharma maker AdvanCell closed a $315M Series D for a lead-based Pluvicto challenger, with Lilly and Sanofi both participating. Lipid nanoparticle startup Nava emerged with $89M. Investors are cutting big checks for early- tage companies in AI, radiopharma, cardiac disease, and gene delivery, and the IPO market is opening back up at the same time. Biotech financing hasn't looked this healthy since 2021.

🔹 The FDA’s acting chief formally walked back former Commissioner Marty Makary’s practice of setting policy through medical journal articles, stating that two such articles published over the past year did not represent agency policy. It’s the latest in a steady reversal of Makary-era actions since his departure in May, and it sharpens the strategic uncertainty for sponsors who had read those articles as signals of the review bar. The timing is worth pointing out. In the same week the agency said Makary’s journal articles were never actual policy, Merck’s oral PCSK9 approval came through on the fast track that Makary himself set up. So companies planning regulatory strategy have to figure out which parts of the Makary era still count. The voucher program and formal guidance clearly do. Informal signals from journal articles clearly don't. And the FDA still doesn't have a permanent commissioner three months in.

🔹 Kelun-Biotech’s TROP2 antibody-drug conjugate sac-TMT, partnered with Merck, hit its primary endpoint in Phase 3 OptiTROP-Lung06, a China trial testing sac-TMT plus Keytruda as first-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer with PD-L1-negative tumors. The combination showed a statistically significant, clinically meaningful improvement in progression-free survival versus standard chemotherapy, with an early positive trend in overall survival. Specific hazard ratios weren’t disclosed at the interim. This matters because PD-L1-negative patients respond poorly to immunotherapy alone, and this trial shows for the first time that an antibody-drug conjugate could anchor a first-line lung cancer regimen without chemotherapy in that group. It’s also the second Chinese trial to work for Merck’s sac-TMT program this year, after OptiTROP-Lung05 in May. Merck now has 17 Phase 3 studies running across breast, lung, gastrointestinal, genitourinary, and gynecological cancers. The open question is whether Western regulators will accept the survival curves from a China-only trial without a global confirmatory study.

🔹 Veradermics reported that its extended-release oral formulation of minoxidil, the active ingredient in Rogaine, worked in women with mild-to-moderate pattern hair loss. Across 28 women dosed once or twice daily for six months, the drug produced a mean increase of about 23 hairs per square centimeter, beating the 15 to 20 analysts had projected, with most patients reporting visible improvement by two months. Shares jumped toward $130 before settling near $116. The extended-release design is meant to sustain drug exposure and avoid the concentration spikes that drive side effects. If this holds up, it could become the first pill specifically approved for female pattern hair loss, a condition affecting roughly 30M American women by some estimates, replacing daily topical foam with a tablet. That said, this is a small single arm signal in only 28 patients with no head-to-head comparison, so the data is encouraging but far from definitive. Phase 3 data in men is expected in the second half of 2026 and the women’s Phase 2/3 in the first half of 2027. Absci’s AI-designed hair loss antibody, backed by Lilly, is the longer-dosing-interval competitor to watch alongside this.

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DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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VIDEO SUMMARY

The video recording platform didn’t record the first few seconds so apologies and Welcome back to Biotech Blueprint :)

THIS WEEK’S KEY TAKEAWAYS 🔑

The biggest story this week was a failure. AstraZeneca and Ionis’s eplontersen missed the primary endpoint of the Phase 3 CARDIO-TTRansform trial in transthyretin amyloid cardiomyopathy, a fatal heart-muscle disease. The market reaction told the story. AstraZeneca fell 8%, Ionis fell 21%, and rivals Alnylam and BridgeBio both jumped double digits. What actually happened is that the standard of care caught up to the trial. By the time CARDIO-TTRansform read out, 57% of patients were already on a protein-stabilizer drug (Pfizer’s Vyndamax or BridgeBio’s Attruby) at baseline, and another 24% started one during the study. Eplontersen worked (29% risk reduction) only in the shrinking group taking nothing else. In transthyretin amyloid cardiomyopathy, a fourth entrant now has to beat a background of drugs that already work, not placebo. Alnylam and BridgeBio didn’t win because they ran a better trial this week but because they were already on the field.

Vertex spent $10 billion this week, its largest deal ever, to buy Crinetics and move beyond the cystic fibrosis franchise that still generates more than $10 billion a year. The same dynamic showed up in kidney disease, where Vera Therapeutics won accelerated FDA approval for Trutakna (atacicept) in immunoglobulin A nephropathy, the second drug of its kind to market after Otsuka’s Voyxact, but with the deeper dataset and a higher price. In both cases the message is the same. Being first is worth less than being better and payers will price the difference.

Two other themes worth flagging this week. First, obesity is truly shifting from an efficacy story to a tolerability story. Kailera and Hengrui’s oral GLP-1 pill hit its Phase 3 goals in China but with nausea and vomiting rates near 70%, which one analyst called alarming. Second, the pace of Western deals with Chinese biotechs isn't slowing down, even as Washington moves to restrict them. AstraZeneca and GSK both signed deals with Sino Biopharmaceutical this week, adding to roughly 100 Western-Chinese transactions since early 2025, the exact pattern that new legislation is trying to slow.

Finally, individualized medicine got real money. ARPA-H committed up to $160 million to seven labs to build custom gene-editing treatments for rare diseases, an attempt to turn the one-off “Baby KJ” success into a repeatable process. In the same week, Prime Medicine won an arbitration ruling against Beam that clears its lead gene-editing program to keep moving. Custom, one-off gene editing is starting to move from proof of concept to actual funded infrastructure.

Biotech/Pharma News 🧬

🔹 Vertex agreed to acquire Crinetics for $85 per share in cash, a 102% premium and the fourth largest biotech acquisition of 2026. The two endocrine drugs Vertex is buying are Palsonify (paltusotine), an oral therapy for acromegaly approved in September 2025 that pulled in $10M in Q1 revenue and is pacing toward roughly $70M this year, and atumelnant, a late stage candidate for congenital adrenal hyperplasia and Cushing’s syndrome. Vertex projects combined peak sales above $5B. This is the clearest statement yet that Vertex intends to become a multi-franchise specialty company rather than the cystic fibrosis only company it has been, adding endocrinology to recent moves in pain (Journavx) and kidney disease. Not everyone loved the price. Stifel called the deal a bet on the “bullish case,” flagging competition from Pfizer and Novartis on the acromegaly side and Neurocrine’s Crenessity against atumelnant, and Vertex stock ticked down on the news. Vertex is sitting on cystic fibrosis cash and facing eventual competition there, so the calculation is that overpaying for de-risked commercial and near-commercial assets today beats waiting. Closing is expected in Q3.

🔹 The FDA granted accelerated approval to Vera Therapeutics’ Trutakna (atacicept) to reduce proteinuria in adults with primary immunoglobulin A nephropathy, a progressive kidney disease affecting about 160k Americans. Trutakna is a once weekly self-injected antibody that blocks two immune signals, BAFF and APRIL, and is the first approved drug to hit both. In the ORIGIN 3 trial it cut urine protein 46% from baseline at 36 weeks, a 42% reduction versus placebo. Because this is accelerated approval based on a surrogate endpoint, Vera still has to prove the drug preserves kidney function over time, with confirmatory data expected in Q3. The commercial fight is a head to head with Otsuka’s Voyxact, which reached market last year and targets APRIL alone with monthly dosing. Vera priced Trutakna at $425k a year against Voyxact’s roughly $390k, betting that a broader mechanism and a stronger dataset justify the premium. Two drugs competing on data quality and dosing convenience rather than novelty is the market Vera has just entered.

🔹 GSK terminated its neurodegeneration alliance with Alector, ending a partnership once worth up to $2.2B (including a $700M upfront in 2021). Both assets failed. Latozinemab, a progranulin-boosting antibody for frontotemporal dementia in patients with specific mutations, failed to slow disease in its late stage trial last October, and Alector halted a Phase 2 study of nivisnebart in early Alzheimer’s on a futility analysis in April. The collapse is a real setback for GSK’s tentative return to brain diseases after more than a decade on the sidelines. For Alector it’s closer to a survival question. The company also lost a separate AbbVie collaboration, has cut staff repeatedly, and has seen its stock fall about 95% over five years. Progranulin biology has been one of neurology’s more credible genetic hypotheses for years, but it hasn’t translated into a disease-modifying win, and large cap partners are no longer willing to keep paying to find out.

🔹 Two of the biggest UK drugmakers signed China deals in the same week. AstraZeneca paid $200M upfront, with up to $1.9B in milestones plus royalties, for ex-China rights to TQC3721, a Sino Biopharmaceutical inhaled lung drug that has cleared Phase 2 in chronic obstructive pulmonary disease with better lung function than standard therapy. That positions AstraZeneca against Merck’s Ohtuvayre, which Merck acquired by paying $10B for Verona Pharma. GSK separately handed Sino the China rights to distribute its marketed respiratory drugs Trelegy (£3 billion in 2025 global sales) and Anoro. These deals land in the middle of roughly 100 Western-Chinese pharma deals since early 2025, and the exact scrutiny that count has provoked. Proposed US legislation would subject outbound investment in Chinese biotech to national-security review. Even as policymakers try to slow the China licensing channel, the economics keep winning. Faster, cheaper, later-stage assets are enough for big pharma to keep signing.

🔹 MeiraGTx secured up to $400M from Oberland Capital in a royalty and financing arrangement to support its late stage eye gene therapies, one of which it recently reacquired from Johnson & Johnson (bota-vec, for X-linked retinitis pigmentosa). The interesting part is the structure. This is another example of revenue and launch-stage biotech reaching for non-dilutive private capital (royalty monetization, structured credit) rather than selling shares, even with public markets wide open. It follows the same logic as BridgeBio’s $1B preferred equity for its amyloidosis launch and Blackstone’s royalty deals. For companies with visible commercial catalysts, giving up future royalties looks cheaper than giving up equity today.

🔹 ARPA-H committed up to $160M through a program called THRIVE to seven research teams building custom gene-editing treatments for rare diseases across multiple organ systems, with the teams required to reach the clinic by year three. THRIVE is an explicit bet that the widely covered “Baby KJ” case, in which an infant received a one of a kind editing therapy, can become a repeatable manufacturing and regulatory pathway rather than a single exception. Custom, N of 1 gene editing has been the frontier the field has been circling for years. Federal money is now trying to industrialize it.

🔹 The White House is reviewing three finalists to run the FDA, suggesting a decision may finally be near after months without a permanent commissioner since Marty Makary’s May departure. In parallel, the agency paused its practice of publicly releasing the letters that explain why it rejects drugs, following a citizen petition from an unnamed pharma company, while it works to formalize the policy. The transparency reversal is small but telling. The short-lived experiment in publishing complete response letters, meant to demystify rejections, is on hold. And the leadership vacuum that has shadowed PDUFA timing all summer may soon lift. Both matter for how predictable the regulatory path looks in the back half of 2026.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

The most important number this week is one Roche didn’t release. Its KRAS G12C inhibitor divarasib beat both approved drugs in the class, Amgen’s Lumakras and Bristol Myers Squibb’s Krazati, in a single Phase 3 trial, improving both overall survival and progression-free survival in previously treated lung cancer. The company held back the actual hazard ratios for a medical meeting, but the design is the story. Roche didn’t run against placebo or chemotherapy but it ran against the two incumbents at once and won. That’s now the third head to head superiority readout in seven weeks, after Takeda’s zasocitinib topped Bristol Myers’ Sotyktu in psoriasis and Akeso’s ivonescimab beat an active PD-1 inhibitor in lung cancer. Beating standard of care used to mean beating whatever came before the current drugs. Now it increasingly means beating the current drugs, and sponsors who are confident in their molecule are choosing to prove it directly rather than lean on cross trial comparison.

The SPDR S&P Biotech ETF (XBI) is up about 30% year to date and rose roughly 19% in June alone, a five-year high that’s closing in on the February 2021 peak of 175. BridgeBio pulled in up to $1 billion in structured capital to fund a commercial launch without selling common stock at a discount. Abivax cleared a cancer safety cloud, watched its shares jump about 40%, and raised $800 million the same week. Ipsen bought two clinical stage biotechs in three days. When the market is this strong, companies aren’t fighting to raise money anymore. They’re fighting to execute, which happens to be the environment that rewards clean head to head data.

The week’s structural signal came from outside pharma. Anthropic launched Claude Science, an AI research workbench aimed squarely at drug company research operations, and disclosed that it will start discovering its own drugs, beginning with neglected diseases the industry ignores. Isomorphic Labs and Recursion have been on this arc for years, but they were biotech native startups.

Underneath everything else, cell and gene therapy kept quietly racking up approvals. Vertex’s Casgevy became the first gene therapy cleared for children as young as two with sickle cell disease. The FDA approved TREGZI, the first regulatory T cell therapy for chronic graft-versus-host disease. United Therapeutics bought a thymic cell therapy platform. None of these was a blockbuster event by itself, but together they show the pattern. The modalities that Section 232 tariffs exempt are also the ones the agency keeps clearing without drama.

Biotech/Pharma News 🧬

🔹 The FDA approved Viridian Therapeutics’ Lumvoa (veligrotug) for thyroid eye disease, and the label is the prize. Like Amgen’s Tepezza, Lumvoa targets the insulin-like growth factor 1 receptor, the inflammation driver behind the disease. But the approval covers both active and chronic thyroid eye disease, where Tepezza’s indication is narrower, and Lumvoa’s regimen is five 30 to 40 minute infusions every three weeks against Tepezza’s eight infusions of up to 90 minutes each. Jefferies pegs pricing near $450k, comparable to Tepezza, so Viridian isn’t buying share with a discount. It’s offering the same mechanism with a lighter treatment burden and a wider label. Leerink’s Thomas Smith argued the combination could expand the treated market rather than just split it. Amgen now has to defend Tepezza against a cleaner competitor, with Immunovant’s subcutaneous IGF-1R candidate still behind them both.

🔹 Ipsen bought Memo Therapeutics for about $800M, roughly €200M upfront plus more than €500M in milestones, for potravitug, an antibody against BK polyomavirus in kidney transplant patients. There’s no approved targeted treatment for the virus, potravitug showed viral suppression and nephropathy resolution in Phase 2, and a pivotal Phase 2/3 trial is expected to start later this year. Two days earlier Ipsen agreed to buy Kartos Therapeutics for $450M upfront and up to $1.3B in milestones, adding a late stage myelofibrosis asset. Ipsen’s rare disease unit generated only about €384M in 2025 against €2.5B+ in oncology, so this is Ipsen deliberately building a third leg. Two deals in a week fits the pattern of European mid-caps assembling clinical inventory ahead of the July 31 Section 232 tariff date.

🔹 Anthropic released Claude Science, a research workbench that connects to more than 60 scientific databases and ships with toolkits for genomics, protein structure analysis, and chemistry, pitched to pharmaceutical research teams the way Claude Code was pitched to software teams. Anthropic will also begin discovering its own drugs, starting with neglected diseases that traditional developers avoid, and demonstrated the system autonomously proposing candidates for phenylketonuria, a rare metabolic disorder. So the largest AI model maker is now competing with its own customers, at least in one narrow segment. It’s a low stakes entry, since neglected diseases carry little commercial threat to pharma companies, but the bigger message is that Anthropic thinks its tools are ready to run the discovery process end to end, not just help someone else do it faster. The credibility test is still a clinic-ready candidate, and the first AI-originated Phase 1 readouts are expected around the end of 2026.

🔹 Abivax released additional Phase 3 safety data showing that malignancy rates for obefazimod, its oral ulcerative colitis candidate, matched background rates for ulcerative colitis patients generally across more than 1,700 patient years of exposure. That directly addresses the cancer cases at the highest dose that crashed the stock in June. Leerink’s Thomas Smith concluded there was “no real malignancy signal” beyond the elevated cancer risk this population already carries from chronic inflammation. Shares surged nearly 40%, and Abivax used the reopening to complete an $800M offering, with an FDA filing planned by year end. The company has drawn reported takeover interest it publicly downplays. Obefazimod’s remission data (roughly 51% versus 10% placebo in maintenance) were never the question. The safety data was, and it just got answered.

🔹 Three separate cell and gene therapy actions extended the modality’s momentum this week. Vertex’s Casgevy became the first gene therapy approved for children aged two and older with sickle cell disease or transfusion-dependent beta thalassemia, pushing the CRISPR therapy into a younger population. The FDA approved TREGZI, the first regulatory T cell (Treg) immunotherapy, to improve chronic graft-versus-host disease-free survival in blood cancer patients receiving allogeneic stem cell transplants. And United Therapeutics bought Thymmune for $140M upfront plus up to $160M in milestones for THY-100, a cell therapy that converts stem cells into thymic cells to restore T cell production in congenital athymia. Individually minor but together they confirm that the tariff exempt modalities keep clearing the agency while conventional biologics wait on the Section 232 clock.

🔹 Roche’s oral KRAS G12C inhibitor divarasib beat both Amgen’s Lumakras and Bristol Myers Squibb’s Krazati in previously treated non-small cell lung cancer patients whose tumors carry the KRAS G12C mutation, which appears in about 14% of cases. The Phase 3 Krascendo-1 trial reported statistically significant improvements in both overall survival and progression-free survival against the two approved comparators, with no new safety findings and side effects described as manageable and reversible. The specific hazard ratios were deferred to an upcoming medical meeting, which is the one caveat. Without the magnitude, it’s too early to say whether this is a modest edge or a class reset. What isn’t in doubt is the design choice. Roche took on both incumbents simultaneously and cleared them on the hardest endpoint. The bigger prize is Krascendo-2, testing divarasib plus Keytruda in the first-line setting, where the market is far larger. Winning second-line sets Roche up. First-line is where they’d actually take the class.

🔹 Otsuka’s Voyxact stabilized kidney function and showed evidence of improvement after two years versus placebo in IgA nephropathy, completing the dataset required for traditional (rather than accelerated) approval. IgA nephropathy has become one of the more crowded rare disease races, and the two year confirmatory readout matters because it converts a surrogate-based accelerated pathway into durable clinical evidence. That’s exactly the surrogate to clinical translation the FDA has been demanding across programs this quarter. For Otsuka, it’s a reminder that its nephrology franchise is quietly delivering the long term data that separates approvable from durable.

🔹 BridgeBio raised up to $1B in preferred equity from Sixth Street Partners ($800M) and HealthCare Royalty ($133.9M) to fund the commercial push behind Attruby (acoramidis) in transthyretin amyloid cardiomyopathy. The structure carries a 7% initial preferred dividend, with a conversion price starting at $137.79 per share and stepping up to $153.10 after five years. The reason this matters isn’t the size of the raise but the structure. BridgeBio didn’t sell common stock into the market and dilute existing shareholders. It borrowed against future cash flows to scale its commercial reach. That’s the same structured capital playbook Blackstone ran with Apogee in May, but applied to a company that already has a drug on the market. When you’re already selling a product, nondilutive financing beats a cheap equity raise every time, even when the equity window is open.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, get in touch.

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👥 If you haven’t already, please connect with me or follow me on LinkedIn.

VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

You could watch the central tension of this week play out on a single day. On Monday, the Department of Health and Human Services published a blueprint called Operation TrialBlazer, designed to pull early stage drug research back onto US soil and close the roughly 18 month head start China holds in moving a molecule from discovery into the clinic. Two days later, Lilly committed up to $1.9 billion in a multi target discovery deal with Abbisko, a Shanghai-based biotech. Washington is trying to make US drug development faster while the money keeps flowing to the place that’s already fast.

What’s changed is that Washington has stopped trying to only wall China off and started trying to outcompete it. The 2024 Biosecure Act didn’t slow China’s rise and lawmakers know it. So the response this week was about making US development more attractive, not punishing companies for working with China. Operation TrialBlazer promises clearer FDA expectations before an investigational new drug filing, fewer redundant toxicology requirements, more flexible trial protocols, and a consultation pilot to speed institutional review. Scott Gottlieb, the former FDA commissioner, put it plainly: “the time and cost advantage can’t tilt so heavily against US-based trials or we’ll lose our edge.” The thing nobody wants to say out loud is that it already has tilted, and a blueprint isn’t going to rebuild a clinical trial ecosystem in a quarter.

The deals from this week tell you where speed actually lives right now. Lilly-Abbisko was the headline, but Ollin Biosciences raised $330 million to push a China-licensed challenger to Roche’s Vabysmo through Phase 3, and Serapha Bio launched on a China-sourced in vivo base-editing program. US and European pharma keep buying de-risked, fast moving chemistry from Chinese developers, while US policy scrambles to make domestic development competitive enough that the next generation of those molecules originates here instead. Both dynamics are running in parallel, and this week they were running right next to each other.

The other thread worth pulling on is Lilly itself, which appeared in three separate deals in five days: the $1.9 billion Abbisko pact, a $40 million equity check into AI design startup Absci, and a $50 million stalking horse bid for the platform assets of bankrupt Sangamo. Lilly is reconstructing its pipeline faster and more opportunistically than anyone else in the industry. Underneath all the deal flow is a quieter macro fact that’s worth holding onto: US health spending hit $5.7 trillion in 2025, up 7.3%, with GLP-1 demand explicitly named as a driver. The bill for the obesity revolution is now showing up in the national accounts, and that’s the backdrop everyone in this space has to operate against.

Biotech/Pharma News 🧬

🔹 HHS published a reform blueprint called Operation TrailBlazer on June 23 built around one competitive problem. A US drugmaker can take far longer than 18 months to move a molecule from discovery into a clinical trial, while China routinely does it inside that window. The proposed fixes are procedural but real. The FDA would specify required data before an IND filing to cut redundant toxicology and chemistry work, allow more flexible trial protocols to reduce amendment filings, and run a consultation pilot that lets developers engage research institutions during IND preparation. NIH would push telehealth, remote monitoring, real-world data, and AI to widen enrollment into rural and underserved areas. There’s even an examination of whether trial participant stipends beyond expense reimbursement are legal under anti kickback rules. The 2024 Biosecure Act tried to slow China down by restricting access. This blueprint takes the opposite approach and tries to make US drug development competitive enough that companies don’t need to look abroad. Whether it actually works depends on execution inside an FDA that has cycled through multiple commissioners and senior reviewers over the past few months, which is exactly the kind of capacity that procedural reform assumes is intact.

🔹 Lilly agreed on June 23 to pay Abbisko Therapeutics an undisclosed upfront plus up to $1.9B in milestones, with tiered royalties, for discovery and early development across multiple undisclosed targets. The deal builds on a 2022 small molecule collaboration between the two companies, so this is a continuation. The timing matters. Hours after the HHS blueprint announcement, the most acquisitive company in pharma chose to widen its bet on Chinese discovery chemistry instead of pulling work back to the US. Abbisko, based in Shanghai, runs the discovery and early development. Lilly holds the development and commercial economics. It’s the same licensing arbitrage model that BMS-Hengrui, Pfizer-Kailera, and Merck-Terns institutionalized over the past year, except now it carries added regulatory timing risk as lawmakers lay the groundwork for legislation that would mandate Treasury and Defense review of pharma deals with Chinese counterparts.

🔹 Novartis ran the domestic version of the same playbook on the same day, paying Antares Therapeutics $105M upfront and up to $1.8B in milestones, plus royalties, to generate small molecules against historically undruggable oncology targets. Antares is exactly the kind of US story Operation TrialBlazer is rooting for. It spun out of Scorpion Therapeutics in June 2025 with $177M in funding, after Scorpion sold a drug program to Lilly for up to $2.5B. Scorpion built its reputation by finding hidden binding pockets, including on PI3K-alpha, and Antares carries that toolkit forward. Its lead oncology program is expected to enter human testing in 2026. Put Novartis-Antares next to Lilly-Abbisko and you get the week’s competitive map in two transactions. Big pharma will pay roughly the same nine figure upfront and ten figure biobucks for fast discovery chemistry whether it sits in Boston or Shanghai.

🔹 Sangamo Therapeutics, one of the original zinc-finger gene-editing companies, filed for Chapter 11 in Delaware on June 23 and lined up initial buyers to anchor an auction of substantially all its assets. Lilly agreed to pay $50M plus assumed liabilities for Sangamo’s capsid delivery platform, zinc-finger platform, modular integrase platform, and its ST-506 prion disease program. Astellas separately agreed to $25M at closing plus up to $25M in milestones for the Fabry disease program ST-920. This is the gene therapy shakeout playing out as a fire sale. A foundational platform company that couldn’t fund itself through to commercial value, with its technology getting absorbed by deep pocketed buyers at distressed prices. For Lilly, $50M buys an entire delivery and integrase toolkit to feed its expanding genetic medicine ambitions, the kind of price only available when the seller is in bankruptcy court.

🔹 Lilly also led a $100M stock offering in Absci, buying $40M of equity. The 13.5M shares priced at $7.41, and Absci shares surged on the news alongside accompanying early clinical data. The money funds ABS-201, an AI-designed antibody being developed for both pattern hair loss and endometriosis. The asset’s selling point is durability. It showed a long lasting presence in the body, which could mean only a few injections per year, a meaningful convenience advantage in a cash pay aesthetic category. Initial proof of concept hair loss data are expected in the second half of 2026, with fuller results in early 2027. For Lilly this is a small optionality bet that checks two boxes the company clearly cares about, AI-driven drug design and a large consumer paid market, for the price of a rounding error.

🔹 US national health expenditure reached $5.7 trillion in 2025, a 7.3% increase and nearly $16,500 per person, according to figures published in Health Affairs on June 24. Government actuaries flagged hospital services and high priced prescription drugs, with GLP-1s explicitly named, and noted that utilization rather than unit price growth is what’s accelerating the trend. Spending is projected to top $6 trillion in 2026, with prescription drug outlays alone expected to exceed $560B next year, up 8.2% and growing faster than any other major category. The obesity drug boom is now showing up in the national accounts, not just in Lilly’s and Novo’s revenue lines. That shifts the political and payer conversation from whether these drugs work to who pays for what is becoming a permanent multi hundred billion dollar line item. The affordability constraint that has been building all year now has a federal number attached to it.

🔹 Pfizer’s sigvotatug vedotin, an integrin beta-6 targeting antibody-drug conjugate, failed its Phase 3 trial in second-line non-squamous non small cell lung cancer. The drug didn’t meaningfully extend overall survival versus docetaxel chemotherapy. Pfizer deferred specific numbers to a future medical meeting. The target was attractive on paper, since integrin beta-6 is expressed on roughly 90% of tumors, but a miss against standard chemotherapy is a miss. This is also a Seagen asset, and Pfizer has now absorbed about $4.5B in write offs tied to Seagen-acquired programs. The readout cuts deeper than one trial. It raises real questions about the return on Pfizer’s $43B Seagen acquisition. The drug’s surviving shot is a first-line combination with Keytruda, with data expected in 2027 in a different comparator and patient population. Early-line combinations sometimes rescue ADCs that have failed as monotherapy in later lines, but that’s a 2027 question now, not a 2026 one.

🔹 Two smaller deals reinforced the China-sourcing pattern this week. Ollin Biosciences raised $330M in a Series B to push a China-licensed challenger to Roche’s Vabysmo through Phase 3 in retinal disease. Vabysmo is one of Roche’s biggest growth products, used to treat wet age-related macular degeneration and diabetic macular edema, and brought in over $3B last year. Separately, Serapha Bio launched this week with a Series A focused on in vivo base-editing programs licensed from Chinese developers, building on the same lipid nanoparticle delivery approach Intellia validated in hereditary angioedema and Verve is extending in cardiovascular disease. Both companies are using the same playbook that defined this week. US capital plus Chinese discovery chemistry, pushed through Western regulatory and commercial channels. The launches don’t move the market on their own, but they show the licensing arbitrage model isn’t just happening at the large-cap level. It’s now the default starting position for new US biotech entrants too.

🔹 A more uncomfortable Lilly story closed out the week. Back in April, the FDA and Lilly granted compassionate-use access to retatrutide, the company’s not yet approved triple-G obesity drug, for a 79 year old patient with refractory obesity, obstructive sleep apnea, and pulmonary hypertension. The application was filed by a senior NIH clinician and drew interest from top health officials, which was unusual enough that Senator Maggie Hassan wrote to HHS Secretary Robert F. Kennedy Jr. asking whether the patient was President Trump or someone close to him. The White House said after publication that the application was not for the president. The patient’s identity is still unconfirmed. The compassionate-use pathway is meant for serious, immediately life threatening conditions, and the controversy is less about retatrutide itself than about whether access to experimental medicines runs through clinical need or political proximity. It’s a reputational footnote for the drug today, but a live question about how the FDA’s expanded-access discretion gets used.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

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🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, get in touch.

🌐 For consulting inquiries, please email us or visit BiotechBlueprintConsulting.com.

👥 If you haven’t already, please connect with me or follow me on LinkedIn.

VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

The most interesting thing that happened this week wasn’t a clinical readout or a deal. It was the FDA reversing itself on two products in two days. On Wednesday, uniQure said the agency will accept three year data from a roughly 50 patient Phase 1/2 study as the primary basis for an accelerated approval filing of AMT-130, its gene therapy for Huntington’s disease. The FDA had previously asked for more. A day later, the agency’s vaccines advisory committee voted unanimously that Moderna’s mRNA flu vaccine has a favorable benefit-risk profile, for a product the same agency had refused to even review earlier this year. Both reversals came after Marty Makary and Vinay Prasad left.

It would be easy to read this as the FDA going soft. It’s not. Under acting commissioner Kyle Diamantas, the agency is being selectively flexible on programs where there’s no current alternative. There’s nothing approved for Huntington’s, which is a uniformly fatal disease. mRNA gives the US a faster way to update flu vaccines as strains drift. But in other areas, the bar hasn’t moved at all. Fulcrum’s sickle cell program got sidelined last week on a safety question, and AstraZeneca’s camizestrant in breast cancer is still frozen after a negative advisory vote in April. So the agency isn’t lowering its standards across the board but it seems to be making case by case decisions about where unmet need is high enough to accept less data. For developers, that makes regulatory strategy harder to plan, because the rules now depend on which category your program lands in.

The other big theme is that M&A keeps happening every single week. Biogen bought an immunology startup for up to $1 billion. Jazz signed a T cell engager deal worth up to $4.1 billion. Lilly bought a non-opioid pain developer in what’s now their fifteenth deal of 2026. PwC reported first quarter pharma deal value above $65 billion and called the biopharma ecosystem “back to full health.” Large caps are buying discovery speed and modality breadth instead of building it in house, and they’re doing it before Section 232 pharma tariffs kick in on July 31.

The IPO market is the cleanest bull signal in biotech right now. Kardigan raised $400 million in an upsized offering this week and closed up 38% on its first day of trading. That makes four biotechs to raise at least $400 million via IPO in 2026, the most in any single year since 2021.

BIOTECH/PHARMA NEWS 🧬

🔹 uniQure said the FDA will accept three year data from its Phase 1/2 study of AMT-130 as the primary basis for a Biologics License Application under accelerated approval. The company plans to file in Q3 2026. AMT-130 is an AAV gene therapy delivered directly into the striatum via neurosurgery, designed to lower the mutant huntingtin protein that drives Huntington’s disease. There is no approved therapy for Huntington’s, which makes a filing on a roughly 50 patient dataset a clear signal that the agency will accept a small package when the disease is fatal and untreated. The FDA also indicated it’s open to a concurrent standard of care control in the confirmatory study rather than a sham surgical arm, which is a meaningful concession given the ethics and cost of sham neurosurgery. Shares jumped on the news. The open questions are durability of effect and whether a 50 patient base can carry a label in a heterogeneous, slowly progressing disease.

🔹 The FDA’s vaccines advisory committee voted unanimously that the benefit-risk profile of mFluSiva, Moderna’s mRNA trivalent seasonal flu vaccine, is favorable. The FDA target decision date is August 5. This completes a striking turnaround. The same agency declined to review the same shot earlier this year, and the briefing documents released ahead of the meeting were supportive. If approved, mFluSiva would be the first mRNA-based seasonal influenza vaccine in the US. The practical implication is that mRNA’s core advantage, speed of reformulation against drifting strains, finally gets a US regulatory anchor in flu, the largest vaccine market by volume. For Moderna, this is the proof point that the platform extends beyond COVID. Vaccine politics remain the wild card between a unanimous panel and a final signature.

🔹 Jazz Pharmaceuticals and AbCellera signed a collaboration to discover next-generation T cell engaging multispecific antibodies for gastrointestinal and other solid tumors. AbCellera takes $56M upfront across the first two programs, plus $28M on initiation of a third, with up to $792M per program in option and milestone payments and tiered royalties, totaling up to $4.1B across as many as five programs. T cell engagers have largely worked in blood cancers and struggled in solid tumors, where the targets are less clean and the toxicity harder to manage. Jazz is paying for AbCellera’s antibody engineering platform to solve that problem rather than buying a finished asset. The small upfront and heavily backloaded structure is the standard template for platform deals where the science still has to prove itself.

🔹 Biogen agreed to acquire RayThera, a private developer of small molecule anti-inflammatory drugs, for up to $1B in upfront and primarily clinical and regulatory milestones. The lead candidate is expected to enter Phase 1 in early Q3 2026. This is Biogen’s second sizable deal of the year after the roughly $5.6B Apellis acquisition in March, and it continues a deliberate push into immunology as the company diversifies away from a neurology franchise that has produced two Phase 2b misses in twelve months. The deal structure, small disclosed upfront with most of the value contingent, fits a preclinical stage asset. What Biogen is really buying is optionality in immune-mediated disease at a price that limits downside if the lead program stalls.

🔹 Lilly acquired 4E Therapeutics, an Austin neuroscience company developing oral MNK inhibitors for chronic pain, on undisclosed terms. The lead compound, 4ET1103, targets the MNK-eIF4E signaling pathway in peripheral sensory neurons and is the first MNK inhibitor for pain to reach the clinic. This is Lilly’s second non-opioid pain acquisition in as many years, following the up to $1 billion SiteOne deal in May 2025, which targeted sodium ion channels. It’s also their fifteenth or so deal of 2026 and pushes the year’s committed acquisition capital past $18B. The chronic pain market has been waiting two decades for a credible alternative to opioids, and Lilly is now building optionality across multiple non-opioid mechanisms.

🔹 Kardigan, a cardiovascular drug developer founded by former MyoKardia executives, raised $400M in an upsized IPO, selling 25M shares at $16, the top of its range. Shares closed up 38% at $22, giving the company a market value near $2B. MyoKardia developed Camzyos and was acquired by Bristol Myers Squibb for $13B, so the founder pedigree is direct. Kardigan has now raised close to $1B total in two years, including a $254M Series B in October. It’s the fourth biotech to raise at least $400M via IPO this year, the most in a single year since 2021. The 38% pop on debut is the signal worth watching. The 2026 IPO class is holding its value in the aftermarket, which is what separates a real funding window from a temporary one.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Image source: pharmaphorum.com

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, get in touch.

🌐 For consulting inquiries, please email us or visit BiotechBlueprintConsulting.com.

👥 If you haven’t already, please connect with me or follow me on LinkedIn.

VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

This week belonged to metabolism. The American Diabetes Association meeting in New Orleans pushed the obesity conversation into a new phase. For three years the story has been Lilly versus Novo and this week it became a four player field. AstraZeneca put real Phase 2 numbers behind its oral GLP-1 pill elecoglipron, 10.5% weight loss at 26 weeks rising to 11.8% at 36 with no plateau, and committed to a sprawling Phase 3 program anchoring what it now frames as a $5 billion cardiometabolic franchise. AstraZeneca is now the third large cap with a credible oral incretin in pivotal development, behind Lilly’s Foundayo and alongside Pfizer’s Metsera assets. The efficacy isn’t class leading, but you don’t need to be best in class to compete in this market anymore. You just need to be good enough, which says a lot about how big the opportunity has become.

The most important obesity development this week wasn’t about a drug. More US employers are planning to drop GLP-1 coverage for weight loss in 2027 because too many of their employees are taking the drugs. Real world persistence is the problem nobody likes to talk about: adherence falls from 65% at 120 days to 34% at one year. The efficacy race, retatrutide at 28.3% in 80 weeks, CagriSema at 23% in 84, is happening on top of a reimbursement system that’s starting to give way. The next phase of this market isn’t about who loses the most weight, but who can stay on the drug long enough, and affordably enough, for the weight loss to matter.

Outside of obesity, the week had its share of platform wins and program failures. Novartis got an early payoff from its $12 billion Avidity acquisition with a clean biomarker win for an antisense oligonucleotide conjugate in muscular dystrophy, then doubled down on molecular glues with a second Orionis deal. Takeda’s zasocitinib beat BMS’s marketed Sotyktu head-to-head in psoriasis, the first time one TYK2 inhibitor has shown statistical superiority over another. Meanwhile Sanofi halted a Phase 3 in a rare neuropathy for insufficient efficacy, and Gilead and Merck’s Trodelvy plus Keytruda combination missed in lung cancer even as their once weekly HIV pill succeeded.

Parabilis priced the largest venture-backed biotech IPO in history at $670 million, beating Kailera’s $625 million record from two months ago. The same week, Summit Therapeutics pulled a $500 million share sale a day after announcing it, even though its PD-1/VEGF bispecific ivonescimab headlined the ASCO plenary just two weeks ago. It seems that new stories with strong science are getting funded, but existing companies that haven’t delivered on past wins aren’t.

BIOTECH/PHARMA NEWS 🧬

🔹 AstraZeneca used the American Diabetes Association meeting to convert a licensed asset into a franchise commitment. In the Phase 2 VISTA obesity trial, elecoglipron at 75 mg produced 10.5% mean weight loss at 26 weeks versus 0.6% on placebo, with the curve still climbing to 11.8% at 36 weeks. In the SOLSTICE Type 2 diabetes trial, the same dose cut HbA1c by 1.9% from baseline versus 0.2% on placebo, with 90% of treated patients reaching HbA1c below 7%. No liver safety signals, infrequent discontinuations. The efficacy is roughly in line with, not ahead of, Lilly’s oral orforglipron, which is why some analysts called the pill “relatively underwhelming.” That reading misses the strategy. AstraZeneca is launching the EMBOLD trials in obesity and the ELUMINATE trials in diabetes, including cardiovascular and kidney outcomes studies and a combination with dapagliflozin. A small molecule oral GLP-1 that’s merely competitive on weight but pairs naturally with AstraZeneca’s existing cardio-renal portfolio is a different commercial proposition than a standalone weight loss drug. The obesity market now has four serious players: Lilly, Novo, Pfizer-Metsera, and AstraZeneca. And the fight is no longer about who can produce the biggest weight loss number. It’s about who can win on convenience, combination opportunities, and payer access.

🔹 A growing share of US employers are planning to drop GLP-1 coverage for weight loss in 2027, because too many employees are taking the drugs and the costs have become unsustainable. Real world persistence makes this worse: adherence falls from 65% at 120 days to 34% at one year. The efficacy race between Lilly’s retatrutide and Novo’s CagriSema is happening on top of a reimbursement system that’s starting to give way. The next phase of the market isn’t going to be about who loses the most weight. It’s about who can be taken long enough, and affordably enough, for the weight loss to actually matter.

🔹 Novartis booked two wins on its platform acquisition strategy in one week. First, the biomarker cohort of the FORTITUDE Phase 1/2 trial of del-brax in facioscapulohumeral muscular dystrophy met its primary and key secondary endpoints, with reductions in disease biomarkers indicating strong target engagement and reduced muscle damage. Del-brax is the asset that came through Novartis’s $12B Avidity acquisition that closed in February, and the result validates that price tag while a 200-patient Phase 3 enrolls across the US and Europe. The drug is an antisense oligonucleotide conjugate, extending the modality’s category-defining run into neuromuscular disease after recent wins in hereditary angioedema and metabolic disease. Second, Novartis extended its molecular glue partnership with Orionis Biosciences, paying $40M upfront and up to $1.4B in milestones to apply Orionis’s discovery platform to hard targets. Molecular glues are the cheaper, orally deliverable cousin of the degrader modality that crossed its regulatory threshold this spring with the Veppanu approval. Novartis is buying optionality across both validated and emerging modalities rather than building each in house.

🔹 Gilead and Merck delivered a win and miss this week. The win: the Phase 3 ISLEND-1 and ISLEND-2 trials of a once weekly oral islatravir + lenacapavir regimen met their primary efficacy endpoint with safety comparable to daily standard of care in virologically suppressed patients. This would be the first oral once weekly HIV treatment, a meaningful convenience step that protects Gilead’s core antiviral business against the long acting injectable threat. The miss: the EVOKE-03 trial of Trodelvy + Keytruda versus Keytruda alone in first line PD-L1-high non small cell lung cancer was stopped early, posting a numerical but not statistically significant progression free survival improvement. The miss carries read through beyond Gilead. It lands one week after Merck’s own TROP2 antibody drug conjugate sac-TMT hit in first line lung cancer in a China-only trial, raising the question of whether the TROP2-ADC + checkpoint combination actually works in lung cancer, or whether last week’s win reflects something specific about the comparator and the patient population.

🔹 Parabilis Medicines priced the largest venture-backed biotech IPO on record, selling 33.5M shares at $20 for $670M, beating Kailera’s $625M record set in April. The company, formerly FogPharma and founded by Gregory Verdine, develops helix-shaped peptide drugs called Helicons designed to hit previously undruggable proteins. About $150M will fund the lead asset zolucatetide, a beta-catenin inhibitor heading to Phase 3 in desmoid tumors in the first half of 2027. The IPO extends a 2026 streak of 12 biotech debuts raising more than $4.1B. The same day Parabilis priced, Summit Therapeutics pulled a $500M share sale it had announced just one day earlier, citing market conditions, even though its PD-1/VEGF bispecific ivonescimab headlined the ASCO plenary just two weeks ago. Investors will pay top dollar for fresh precommercial stories and balk at adding to positions that haven’t rewarded prior good news.

🔹 Sanofi halted its Phase 3 MOBILIZE trial of riliprubart in chronic inflammatory demyelinating polyneuropathy after an independent monitoring committee found the study unlikely to show sufficient efficacy. The trial enrolled patients refractory to standard of care. No safety signals were identified. The companion VITALIZE Phase 3 in patients treated with intravenous immunoglobulin will be evaluated separately, but the failure removes one path for a complement-targeting therapy Sanofi had viewed as a potential blockbuster. CIDP is the same indication argenx and others are pursuing, and the futility readout reinforces that mechanistic rationale in autoimmune neurology isn’t translating cleanly into efficacy in refractory patients.

🔹 Takeda’s oral TYK2 inhibitor zasocitinib beat Bristol Myers Squibb’s marketed Sotyktu head-to-head in plaque psoriasis, achieving statistical superiority on all primary and secondary endpoints. At 16 weeks, more than a third of zasocitinib patients achieved complete skin clearance, more than double the rate seen on Sotyktu. This is the second approved therapy zasocitinib has topped, following an earlier win against Amgen’s Otezla. Takeda paid roughly $4B for the asset through its Nimbus Therapeutics deal, and a head-to-head superiority claim against the only marketed oral TYK2 inhibitor is the strongest possible commercial setup. Takeda is targeting a 2026 FDA filing with launch expected in 2027. Sotyktu’s positioning as the premium oral psoriasis option is now directly threatened by a next-generation molecule with cleaner data, before zasocitinib has even reached the market.

🔹 Lilly presented the full TRIUMPH-1 dataset behind its May topline at the ADA meeting. At 80 weeks, retatrutide produced mean weight loss of 28.3% (about 70 pounds) at 12 mg and 25.9% (about 64 pounds) at 9 mg in obesity without diabetes. The triple agonist hitting glucagon, GLP-1, and GIP receptors also showed superior HbA1c and weight reductions versus placebo in the TRANSCEND-T2D-1 diabetes study, with added improvements in systolic blood pressure and lipids. The 28% efficacy ceiling retatrutide set is now reinforced with full peer-presented data, and it reframes every competitor. Novo’s CagriSema, at 23% over 84 weeks, sits a tier below, and Novo’s chief scientific officer publicly conceded the jury is still out on how CagriSema stacks up against the tri-agonist. The retatrutide program now spans diabetes, obesity, sleep apnea, MASH, and cardiometabolic outcomes, making it less a drug and more a metabolic platform.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Image source: Angus Liu/Fierce Pharma

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, get in touch.

🌐 For consulting inquiries, please email us or visit BiotechBlueprintConsulting.com.

👥 If you haven’t already, please connect with me or follow me on LinkedIn.

VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

ASCO 2026 was the meeting where Chinese oncology stopped being a sourcing story and became a science story. For the first time in the society’s 61 year history, a drug that originated in China took the plenary stage. Akeso’s ivonescimab, a bispecific antibody that targets both PD-1 and VEGF simultaneously, beat an active PD-1 inhibitor head to head in first line squamous lung cancer and cut the risk of death by 34%. The comparator wasn’t placebo or chemotherapy. It was an approved checkpoint inhibitor, which makes this a Chinese asset setting a new global standard, published in The Lancet the same day. Behind it came two more positive China-run Phase 3 oncology readouts the same week: Bristol Myers Squibb’s bispecific antibody-drug conjugate cutting progression risk by 71% in triple-negative breast cancer, and Innovent’s claudin-targeted conjugate hitting its endpoint in gastric cancer. The center of gravity in oncology drug origination has visibly shifted east.

Washington noticed. Days after ASCO ended, a bipartisan House bill moved to fold biotechnology into the Comprehensive Outbound Investment National Security Act, which would subject US investment in Chinese biotech to national security review. The bill follows the Pfizer-Metsera and BMS-Hengrui deals from the past two months, and the framing is that Chinese drug development progress is now a security exposure. If it passes, it would put friction on exactly the licensing channel that Lilly, Merck, AstraZeneca, and BMS have been using to buy discovery speed at a discount. The cheapest, fastest moving early stage oncology data in the world is increasingly Chinese, and the US is now trying to restrict the capital that brings it onshore. Any large cap company actively negotiating a China asset deal just picked up a new timing risk.

Revolution Medicines was the Western story of the week. Daraxonrasib confirmed a doubling of overall survival in previously treated metastatic pancreatic cancer at the ASCO plenary, 13.2 months versus 6.7 months on chemotherapy, hazard ratio 0.40. Pancreatic cancer is one of the indications that has resisted progress for a generation, and the result drew a standing ovation. The more interesting signal is commercial. Patients and oncologists are already pressing for access to a drug that hasn’t been approved yet, which is something most oncology programs never have to deal with.

Lilly kept buying modality breadth while pushing back on pricing pressure. An RNA exon-editing deal with Ascidian worth up to $1.9B, a Korean GLP-2 obesity asset from Hanmi, a five program option deal with China’s Haisco, an ultimatum to 340B hospitals on discount data sharing, and a billion dollar cut to planned German manufacturing in response to German pricing reform. And in immunology, Abivax posted the best Phase 3 ulcerative colitis efficacy of the cycle and the stock got crushed anyway, because the safety table had cancer cases in it. A reminder that efficacy doesn’t clear the gate on its own when a chronic, non-life-threatening disease meets an oncogenic signal.

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🔹 Akeso’s ivonescimab became the first China-originated oncology drug ever selected for the ASCO plenary, with Phase 3 HARMONi-6 data showing it reduced the risk of death by 34% in first line advanced squamous non-small cell lung cancer versus tislelizumab, an active PD-1 inhibitor. Median overall survival hit 27.9 months, a 4.2 month improvement after 21.4 months of follow-up. Ivonescimab is a bispecific antibody that targets PD-1 and VEGF at the same time, and the results were published in The Lancet simultaneously with the presentation. This is the first regimen to show a survival edge over a checkpoint inhibitor in first line squamous disease. The geographic caveat stands. HARMONi-6 enrolled entirely in China, and Summit Therapeutics holds the US and ex-China rights and still needs Western confirmatory trials to convince the FDA. But the mechanism question is settled in a way it wasn’t before. A PD-1/VEGF bispecific can outperform the checkpoint inhibitors that currently define standard of care.

🔹 Bristol Myers Squibb’s izalontamab brengitecan, the EGFR-by-HER3 bispecific antibody-drug conjugate the company paid $800M for in 2023, posted positive Phase 3 data in the China-based PANKU-Breast02 study in previously treated metastatic triple-negative breast cancer. The drug cut the risk of progression or death by 71% versus chemotherapy and produced a 51.7% response rate against 20.5% for chemo, hitting both progression-free and overall survival co-primary endpoints. This is the first bispecific antibody-drug conjugate to clear dual primary endpoints in this setting. The competitive read for the marketed TROP2 conjugates, Gilead’s Trodelvy and the recently approved Datroway from AstraZeneca and Daiichi Sankyo, is direct. They now face a dual-target conjugate with a more potent payload landing harder on response rate.

🔹 Representatives John Moolenaar and Debbie Dingell introduced a bipartisan House bill to add biotechnology to the Comprehensive Outbound Investment National Security Act, which would require national security review of US investment in Chinese biotech. The bill follows the Pfizer-Metsera and Bristol Myers-Hengrui deals from the past two months and frames Chinese drug development progress as a security exposure. The practical effect, if it passes, would be friction on exactly the licensing channel that Lilly, Merck, AstraZeneca, and Bristol Myers Squibb have been using to buy discovery speed at a discount. ASCO proved the science is real. Washington responded by trying to gate the money. Companies mid-negotiation on China assets now carry a regulatory timing risk that didn’t exist a quarter ago.

🔹 Revolution Medicines confirmed the pivotal Phase 3 RASolute 302 result at the ASCO plenary: median overall survival of 13.2 months on oral daraxonrasib versus 6.7 months on chemotherapy in previously treated metastatic pancreatic cancer, a hazard ratio of 0.40 with p less than 0.0001. Progression-free survival was 7.2 months versus 3.6. Daraxonrasib is a multi-selective RAS inhibitor dosed at 300 mg once daily, and the survival doubling in an indication where median survival has barely moved in decades drew a standing ovation from the audience. The more telling signal is commercial. STAT reported that patients and oncologists are already pressing for access to a drug that hasn’t been approved, and analyst conversations have shifted from whether daraxonrasib works to how far the franchise expands into earlier lines and first-line use. That is a quality of problem most oncology programs never reach.

🔹 Lilly had another busy week of M&A on multiple fronts. The headline deal was an RNA exon-editing collaboration with Ascidian Therapeutics worth up to $1.9B for genetic kidney diseases. Lilly also took most rights to Hanmi’s GLP-2 obesity candidate sonefpeglutide, optioned up to five programs from China’s Haisco, and extended its delivery technology pact with Camurus. The GLP-2 mechanism is a new metabolic lever distinct from the GLP-1/GIP axis that defines Zepbound, fitting the pattern of buying adjacency rather than more of the same. At the same time, Lilly issued a data sharing ultimatum to 340B hospitals, demanding proof they are not double dipping discounts or losing access to them, and cut its planned German manufacturing investment by at least $1B in response to German drug pricing reform. Boehringer Ingelheim made a similar cut on the same day. Lilly is spending freely on modality breadth while using its scale to push back hard on any policy that compresses net pricing.

🔹 Alnylam signed a three year AI deal worth up to $2B with Inceptive Nucleics, with $30M upfront in cash and equity, to build RNA foundation models. Inceptive was founded by Jakob Uszkoreit, one of the co-authors of the original transformer architecture paper that underpins modern large language models. The aim is to design and prioritize RNAi therapeutics computationally rather than empirically. The deal sits alongside NewLimit’s $435M round for epigenetic reprogramming, with Lilly Ventures participating, as evidence that AI and biology capital is now flowing to incumbents buying compute capability, not just to startups selling it. The small upfront, large milestone ceiling structure treats AI design as a high option, low commitment bet.

🔹 Abivax’s obefazimod, an oral miR-124 enhancer in ulcerative colitis, hit its Phase 3 ABTECT maintenance primary endpoint cleanly. The 25 mg and 50 mg doses produced clinical remission at Week 44 in 50.8% and 51.3% of patients respectively versus 10.4% on placebo, a roughly 40-point placebo-adjusted gap that is among the strongest ever reported in ulcerative colitis, with all key secondary endpoints met. The market sold the stock hard anyway, because the safety table reported cancer cases among treated patients, concentrated at the high dose. This is the immunology evidentiary bar in its purest form: efficacy alone doesn’t clear the gate when a chronic, non-life-threatening disease meets an oncogenic safety question. Abivax, a reported takeover target, plans an FDA filing in Q4 2026, and the label fight will be about dose and malignancy monitoring, not whether the drug works.

🔹 Celcuity presented full Phase 3 VIKTORIA-1 data showing its gedatolisib triplet extended median progression-free survival to 11.1 months versus 5.6 months for alpelisib plus fulvestrant in PIK3CA-mutated, HR-positive/HER2-negative advanced breast cancer, a 50% reduction in progression risk. The doublet matched it at 11.3 months. An investigator called it a potential new standard of care, and gedatolisib, a multi-target inhibitor of the PI3K/AKT/mTOR pathway, clearly beat the existing PI3K inhibitor on the market. The stock fell anyway, because expectations had been set at “transformative” and an 11-month median against an old comparator read as merely good. A useful reminder that in crowded breast cancer, the bar for a clean Phase 3 win is now set by investor narrative as much as by the curve.

🔹 Roche disclosed that giredestrant, its oral selective estrogen receptor degrader, missed in first-line metastatic breast cancer, and is redirecting the program into a new adjuvant Phase 3 rather than abandoning it. The result extends a difficult stretch for the oral SERD class, coming weeks after AstraZeneca’s camizestrant drew a 6-3 ODAC vote against its first-line switch strategy. The pattern is consistent: oral SERDs are struggling to prove first-line benefit against entrenched endocrine backbones, and the survivors are retreating to narrower biomarker-defined or earlier-stage settings where the comparator is weaker.

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Have a great rest of your week and thanks for reading Biotech Blueprint!

DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Image source: Angus Liu/Fierce Pharma

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, get in touch.

🌐 For consulting inquiries, please email us or visit BiotechBlueprintConsulting.com.

👥 If you haven’t already, please connect with me or follow me on LinkedIn.

VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

GSK and Ionis published Phase 3 data in the New England Journal of Medicine showing that bepirovirsen, an antisense oligonucleotide, functionally cured roughly one in five chronic hepatitis B patients across two trials totaling 1,838 patients. The standard of care for the past two decades has been indefinite antiviral therapy that suppresses the virus without ever clearing it. Twenty percent functional cure rates after 24 weeks of dosing is not a marginal improvement. Combined with Madrigal-Arrowhead’s PNPLA3 deal earlier this month and Intellia’s CRISPR Phase 3 win in hereditary angioedema, oligonucleotide modalities have now stacked three category-defining wins in five weeks across virology, metabolic disease, and rare disease.

Lilly’s $3.8 billion vaccine buying spree is the most strategically interesting move the company has made all year. The official framing was about preventing disease at the source rather than treating it later, which reads as polite cover for the real story. Lilly is using GLP-1 cash flow to build franchise breadth it has never had. Curevo’s Phase 2 shingles asset goes directly at GSK’s $4 billion Shingrix franchise. LimmaTech’s Phase 1 Staphylococcus aureus vaccine targets surgical site infections, an indication with no approved vaccine. Vaccine Co.’s preclinical Epstein-Barr virus candidate is a bet on multiple sclerosis prevention. This is Lilly’s tenth acquisition of 2026, and roughly half of those deals are in modalities Lilly does not currently run at scale: gene editing, non-viral delivery, vaccines, dual-payload ADCs. You can read the strategy in the deal flow: buy delivery and infrastructure now, deploy retatrutide cash on indication coverage later.

CVS Caremark reversed its 2025 Wegovy-only obesity formulary this week, adding Foundayo as a covered option starting June 1 and restoring Zepbound as a preferred option October 1, with Wegovy’s products remaining covered. Lilly now has obesity drug coverage across all three major pharmacy benefit managers. The bear case had been that Foundayo’s launch would lag because PBM access was structurally tilted toward Novo, and indeed Foundayo had been pacing at about 30% of oral Wegovy’s six week prescription trajectory. That handicap is now lifted. Lilly shares moved up about 6% on the news. The obesity fight is back to being about efficacy, convenience, and net pricing.

Daiichi Sankyo’s Datroway became the first TROP2 antibody-drug conjugate approved in first-line triple-negative breast cancer this week, with overall survival of 23.7 months versus 18.7 months on chemotherapy. That is the first time any targeted therapy has beaten chemotherapy on survival in this patient population. ADCs are now first line therapy in tumors that have been chemotherapy-only for decades, which is the same trajectory Enhertu took in HER2-positive breast cancer: second-line approval, then label expansion, then first line displacement.

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🔹 GSK and Ionis released full Phase 3 data on May 28 for bepirovirsen in chronic hepatitis B, alongside publication in the New England Journal of Medicine. In B-Well 1, 20% of patients on bepirovirsen plus antivirals achieved functional cure, defined as sustained loss of hepatitis B surface antigen with undetectable viral DNA, versus 0% on placebo plus antivirals. B-Well 2 showed 19%. Cure rates climbed to 25-28% in patients with lower baseline viral protein levels. Patients with undetectable disease at week 48 discontinued standard antiviral therapy. Bepirovirsen is an antisense oligonucleotide developed by Ionis and licensed to GSK. The FDA decision is due October 26. Chronic hepatitis B affects roughly 254M people globally, and the current standard of care, nucleoside analogs, suppresses the virus but rarely eliminates it. A 20% cure rate with a 24-week course is a category redefining number. The open question is pricing and access in the regions where the disease burden is heaviest (China, sub-Saharan Africa, and Southeast Asia).

🔹 Lilly announced three vaccine acquisitions on May 26 worth up to $3.83B in milestone-contingent value. Curevo (up to $1.5B) has a Phase 2 next-generation shingles vaccine using a synthetic adjuvant that has shown comparable immune response with fewer side effects than Shingrix. LimmaTech (up to $780M) has a Phase 1 Staphylococcus aureus vaccine for surgical site infection prevention. Vaccine Co. (up to $1.55B) is preclinical with an Epstein-Barr virus vaccine, which has growing scientific support as a multiple sclerosis prevention target. Upfront amounts were not disclosed. This is Lilly’s tenth M&A move of 2026 and brings 2026 deal spend above $5B across vaccines, gene editing, non-viral DNA delivery, and dual payload ADCs. The strategic frame is that Lilly is treating GLP-1 cash flow as a one-time opportunity to build modality and indication breadth before the next cycle.

🔹 CVS Caremark reversed its 2025 Wegovy-only obesity formulary on May 28, adding Foundayo (oral orforglipron) effective June 1 and restoring Zepbound as a preferred option October 1. Wegovy stays covered. Lilly’s obesity drugs now have coverage across all three major pharmacy benefit managers. The structural handicap on Foundayo’s launch, which had been running at about 30% of oral Wegovy’s early prescription pace, is now lifted. Lilly shares moved up about 6% on the announcement. The commercial competition resolves back to a head-to-head on efficacy, convenience, and net pricing, and Lilly’s retatrutide submissions later this year only widen the efficacy gap.

🔹 Verve Therapeutics, now owned by Lilly, presented Phase 1 data for VERVE-102 at the European Atherosclerosis Society Congress on May 26, with simultaneous publication in the New England Journal of Medicine. The trial enrolled 35 patients across six dose levels. LDL cholesterol reductions ranged from 9% to 62% across doses, with PCSK9 protein reductions of 55% to 88%. Durability of effect held for up to 18 months after a single infusion, the longest follow-up disclosed for any in vivo base editing therapy. No treatment-related adverse events. The top dose effect approaches what Amgen’s Repatha delivers as a chronic biologic that costs about $6k a year. Lilly plans to launch Phase 2 by the end of 2026. The regulatory question has shifted from whether the technology works to whether 18 month durability is sufficient to support a one time administration label rather than periodic redosing.

🔹 Apogee Therapeutics secured up to $1.3B in non-dilutive royalty financing from Blackstone Life Sciences to fund three Phase 3 trials of zumilokibart, an anti-IL-13 antibody, in atopic dermatitis. Phase 2 data showed 66% of mid-dose patients achieved 75% skin clearance versus 23% on placebo. The drug’s structural differentiator is dosing frequency: 2 to 4 injections per year versus every 2 to 4 weeks for Dupixent and Ebglyss. Trials begin in the second half of 2026. The fact that Blackstone is willing to underwrite three Phase 3 trials non-dilutively says something about how the eczema biologic market is now structurally bid for differentiated dosing rather than just efficacy.

🔹 Daiichi Sankyo and AstraZeneca’s Datroway received FDA approval on May 22 in first line metastatic triple negative breast cancer for patients ineligible for checkpoint inhibitor therapy. The Phase 3 trial showed median overall survival of 23.7 months versus 18.7 months on chemotherapy, a hazard ratio of 0.79. This is the first TROP2 antibody-drug conjugate approved in first-line triple-negative breast cancer and the first targeted therapy to show an overall survival benefit over chemotherapy in this population. Datroway now competes against Gilead’s Trodelvy and pushes ADC platforms further into first-line settings that have been chemotherapy-only for decades.

🔹 Biogen and Denali announced that BIIB122, an LRRK2 inhibitor, missed its primary endpoint in the Phase 2b LUMA trial in idiopathic Parkinson’s disease. The partners are ending development in that population. The trial tested whether LRRK2 inhibition slowed motor and clinical progression in idiopathic patients regardless of LRRK2 mutation status, and the answer was clearly no. The parallel LIGHTHOUSE trial in LRRK2 mutation-positive patients continues. For Denali, the commercial story remains AVLAYAH, their brain-penetrant Hunter syndrome therapy launched in April. For Biogen, this is the second neurology Phase 2b miss in twelve months and reinforces a pattern of large cap neurology platforms failing on symptom-progression endpoints despite biomarker rationale.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Image source: Getty Images

🎙️ Biotech Blueprint brings you weekly video updates on the latest biotech and pharma news, plus in-depth podcast interviews with industry leaders. You can find us on YouTube, Spotify, and Apple Podcasts. If you want to be featured on our podcast, get in touch.

🌐 For consulting inquiries, please email us or visit BiotechBlueprintConsulting.com.

👥 If you haven’t already, please connect with me or follow me on LinkedIn.

Treating a new realm of diseases

Beyond traditional limits: explore the drug delivery technology opening new doors in genomic medicine.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

The number that defines this week is 28.3%. That is the average body weight lost on the 12 mg dose of Lilly’s retatrutide in TRIUMPH-1, the first successful Phase 3 readout for the GIP/GLP-1/glucagon triple agonist that has been the most watched obesity asset in the pipeline for two years. A second pivotal trial in patients with knee osteoarthritis hit 28.7% plus a 75.8% reduction in pain scores. We have officially entered the territory where a pill or injection produces weight loss comparable to bariatric surgery. The bear case on incretin pricing pressure may eventually arrive, but the front of the efficacy curve just moved again, and Novo Nordisk’s CagriSema and Pfizer’s Metsera assets now have to be measured against a 30% ceiling rather than a 25% one. The wrinkle worth holding onto is the discontinuation curve. 11.3% of patients on the 12 mg dose dropped out for adverse events versus 4.9% on placebo, which is why the 9 mg arm is probably the commercial sweet spot.

The other big story this week is about how pharma is choosing to build, not what it is building. The same Lilly that posted the retatrutide data also acquired Engage Bio for up to $202 million, its seventh M&A move of 2026, to pick up a non-viral DNA delivery platform. Bristol Myers Squibb signed a strategic agreement with Anthropic to deploy Claude across more than 30,000 employees in a workflow-embedded configuration that goes well beyond a chatbot. Incyte struck two AI deals the same week. The emerging pattern is that large pharma is buying discovery infrastructure now, and enterprise AI has crossed from “nice to have” into table stakes.

Two weeks after Marty Makary’s exit, the FDA story has moved from leadership churn into something more operational. Endpoints published an investigation into the coordinated campaign of biotech executives, lobbyists, and former FDA officials that pushed him out, with Biohaven CEO Vlad Coric as a central figure after his company’s pushback on a late-April complete response letter. On the same day, the acting head of NIAID reportedly stepped down, and NIH Director Jay Bhattacharya was grilled by Senate Appropriations on the 2027 budget. The leadership vacuum is widening, not narrowing. If you have a PDUFA date or a Type B meeting on the calendar this summer, you should probably plan for delays.

Outside obesity and US policy, the most strategically important readout came out of China. Merck partner Kelun-Biotech’s sac-TMT combined with Keytruda cut the risk of tumor progression or death by 65% versus Keytruda alone in first-line PD-L1-positive non-small cell lung cancer. This is the first Phase 3 trial of an antibody-drug conjugate combined with a checkpoint inhibitor to win in first line lung cancer. Keytruda loses patent exclusivity in 2028, and Merck’s strategic response is to convert it into a backbone for combination regimens. Nobody really cares anymore that the asset came from China. The next real test is whether the Western confirmatory study running in parallel reproduces the result.

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BIOTECH/PHARMA NEWS 🧬

🔹 Lilly reported positive Phase 3 topline results for retatrutide, its triple-agonist obesity drug, in adults with obesity or overweight plus at least one weight-related comorbidity without diabetes. After 80 weeks, the 12 mg dose drove 28.3% weight loss, roughly 70 pounds on average, versus 2.2% on placebo. The 9 mg dose delivered about 24% and the 4 mg dose about 19%. Discontinuation rates due to adverse events were 4.1%, 6.9%, and 11.3% across the three doses versus 4.9% on placebo, with nausea, diarrhea, and vomiting as the dominant side effects. A second trial in patients with obesity and knee osteoarthritis hit 28.7% weight loss and a 75.8% reduction in WOMAC pain scores at the high dose. Seven additional retatrutide Phase 3 trials read out through 2026 across diabetes, sleep apnea, MASH, chronic low back pain, and cardiovascular outcomes. Lilly is no longer fighting on the same efficacy frontier as Novo’s CagriSema, which posted 22.7% in a comparable population last year. The likely commercial read is that retatrutide expands the obesity market rather than cannibalizing Zepbound, because the 12 mg discontinuation rate creates real-world dose ceiling effects. Lilly will not run pricing off the 12 mg label.

🔹 Lilly also closed its acquisition of Engage Bio for up to $202M, picking up a non-viral DNA delivery platform that combines engineered DNA payloads with lipid nanoparticles. The aim is to solve the persistent problems with gene therapy delivery: potency, tolerability, and the ability to redose, all of which have constrained the AAV-based approaches Sarepta and others have relied on. This is Lilly’s seventh acquisition of 2026 and continues a clear strategic pattern: the company is treating genetic medicine as a delivery problem rather than a payload problem.

🔹 Endpoints News published an investigation this week describing a multi-month coordinated effort by biotech executives, lobbyists, and former FDA officials that contributed to Marty Makary’s departure on May 12, with Biohaven CEO Vlad Coric featured prominently after Biohaven’s late-April complete response letter on a spinocerebellar ataxia program. The broader regulatory landscape is also fraying. The acting head of NIAID reportedly stepped down, and NIH Director Jay Bhattacharya faced bipartisan Senate scrutiny on the 2027 budget. The practical implications include real delay risk for PDUFA decisions, Type B meeting outcomes, and advisory committee scheduling for at least the rest of the quarter, with small-cap companies under $200 million in cash and active regulatory engagement the most exposed.

🔹 Kelun-Biotech released the OptiTROP-Lung05 Phase 3 abstract ahead of ASCO 2026, reporting a 65% reduction in the risk of tumor progression or death for sac-TMT combined with Keytruda versus Keytruda alone in previously untreated PD-L1-positive non-small cell lung cancer. Sac-TMT is a TROP2-directed antibody-drug conjugate carrying a topoisomerase I inhibitor payload, and Merck licensed ex-China rights from Kelun back in 2022. This is the first Phase 3 of any antibody-drug conjugate plus checkpoint inhibitor combination to hit in first line lung cancer. The competitive read matters as AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan has struggled to convert Phase 3 signals into a first line label, and Merck now has a credible path to turn Keytruda into a combination backbone heading into its 2028 patent expiration. The enrollment was China-only, and Western confirmatory trials are running in parallel, so the question of whether the regional efficacy translates is real. The 65% magnitude is large enough that even a substantial regional discount would still be commercially material.

🔹 BMS signed a strategic agreement with Anthropic to deploy Claude across more than 30k employees globally, with use cases spanning scientific literature summarization, clinical protocol drafting, internal data querying, and routine documentation. The deal also includes Claude Code for research and drug development functions. Combined with Incyte’s two AI deals the same week, it seems that enterprise AI is now baseline infrastructure for top-20 pharma rather than a differentiated capability.

🔹 Immunovant reported Week 16 results from its IMVT-1402 trial in difficult-to-treat rheumatoid arthritis, with ACR20, ACR50, and ACR70 response rates of 72.7%, 54.5%, and 35.8% in patients who had failed at least two prior advanced therapies, including both JAK and anti-TNF inhibitors. Response rates held in the subgroup that had failed both classes. Shares moved on the print. The proof-of-concept readout in cutaneous lupus is expected in the second half of 2026 and will be the next decisive print for the company’s autoimmune blockbuster thesis.

🔹 BioMarin’s Voxzogo hit the primary endpoint in a Phase 3 trial in hypochondroplasia, with annualized growth velocity 2.33 cm per year above placebo at Week 52, opening a second pediatric short-stature indication beyond the original achondroplasia label. Filings are planned for the second half of 2026. Two days earlier, BMN 401, an enzyme therapy acquired in the 2025 Inozyme buyout, missed its radiographic clinical endpoint in ENPP1 deficiency despite hitting on the biomarker co-primary, and will require FDA discussion on surrogate to clinical translation.

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

You can listen to this episode on YouTube, Spotify or Apple Podcasts.

In the latest joint podcast episode by Biotech Blueprint × Biotech Capital Compass, we zoom in on Moderna and where the company stands in 2026. We work through the Q1 earnings beat, the unprecedented FDA refusal-to-file on mRNA-1010, the CMV Phase 3 failure, the Vertex cystic fibrosis wind down, and the individualized neoantigen therapy (INT) program that has moved to the center of the pipeline. The short companion piece below picks up one thread from the conversation, which is the pattern across Moderna’s wins and losses, and what it suggests about where the platform actually works.

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Here’s a link to our previous mRNA podcast episodes:

The successes are all acute. COVID-19, RSV via mRESVIA, the seasonal flu candidate, INT. Each one needs a burst of antigen or a pulse of immune training, and then the body takes it from there. The disappointments are the opposite. CMV is a latent virus that hides intracellularly for life and needs durable, often mucosal immunity to keep suppressed. The Vertex-partnered inhaled mRNA program for CF patients without CFTR protein required continuous replacement of a protein the body cannot make on its own. Both programs were asking the platform to do something it isn’t really built to do.

The biology is straightforward. An mRNA-LNP delivers its cargo into a cell, the ribosomes translate it for a day or two, cytosolic nucleases degrade the mRNA, the LNP clears, and detectable protein is gone within a week or two. Modified nucleosides like N1-methylpseudouridine stretch the translation window a bit and dampen innate sensing, but they do not change the fundamental kinetics. mRNA is, by design, a short-burst technology. That is exactly what you want for a vaccine. It is much harder to make it the right tool for sustained protein replacement, or for the kind of tissue-resident memory T cell response you would want against a virus that is going to live in your body forever.

Hartaj framed the underlying question on the episode this way:

“…One of the things that Moderna is having to go through right now is figure out where is it really that the mRNA modality can work.”

— Hartaj Singh (Biotech Capital Compass)

One way to read the last year of Moderna news is that the platform has been answering that question for them. The successes mark out the shape of what it does well and the failures mark out where it doesn’t. The strategic pivot toward oncology and acute respiratory, and away from latent viruses and chronic protein replacement, looks less like a retreat under cash pressure and more like the company drawing the right roadmap.

That makes INT (mRNA-4157) the cleanest test of where this goes. Each product codes for up to 34 patient-specific neoantigens, selected from tumor sequencing by predicting which mutated peptides will bind that patient’s HLA molecules and present on the tumor surface where cytotoxic T cells can find them. Melanoma is the natural first indication because it carries one of the highest tumor mutational burdens of any solid tumor, which gives the selection pipeline more candidates to choose from. Non-small cell lung cancer extends the test to a much larger patient population. INT plays to what mRNA is good at. A focused immune-training event, then the patient’s T cells do the work. If the melanoma signal holds in NSCLC, the read above is probably right. If it doesn’t, mRNA’s reach is narrower than even this piece is suggesting.

Everything else from the episode is near-term noise. The Q1 earnings beat was helpful but ambiguous, since Q1 is seasonally weak and expectations had been cut. The August 5 PDUFA decision on mRNA-1010 will tell us more about whether the regulatory environment is functionally hostile to mRNA respiratory vaccines under this administration than it will about the trial itself.

One quick teaser for next time. The thread we deliberately did not pull on this week is the role of machine learning in INT. The FDA has indicated it wants the neoantigen selection algorithm submitted as part of the regulatory package, which is the first time we are aware of an AI/ML system being treated as a regulated component of a therapy rather than as a tool sitting upstream of it. That is a bigger story than it sounds, and it gets its own episode.

Three Takeaways

1. Moderna’s successes and failures cluster along one axis. Acute, episodic, pulse-style indications on one side. Sustained, latent, chronic indications on the other.

2. The strategic pivot reads more cleanly as realignment. The company is moving toward indications where the biology fits.

3. INT is the test. The 2026 readouts will tell us whether the platform is broadly useful in oncology, or whether even oncology turns out to be narrower than we hope.

Listen to the full episode on YouTube, Spotify, or Apple Podcasts. Our next episode picks up the thread on AI, machine learning, and what it means when the algorithm itself becomes part of the drug.

Thanks for reading Biotech Blueprint!

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DISCLAIMER: This publication is for informational and educational purposes only and does not constitute investment, legal, medical, or tax advice, a solicitation, or an offer to buy/sell any security. Information is believed reliable but no warranty is made as to accuracy or completeness; views may change without notice. Do your own research and consult qualified professionals.

DISCLOSURE & CONFLICTS: The author may hold positions in securities mentioned and may change positions at any time without notice. No compensation is received from companies mentioned, and there are no known material business relationships unless explicitly stated. Content may reference clinical data and regulatory events; always consult primary sources and a licensed clinician for medical decisions. Past performance is not indicative of future results.

LIABILITY: Use of this content is at your own risk. The author assumes no responsibility for any losses arising from reliance on this material.

Photo credit: Moderna