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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Revolution Medicines sold $197.6M of Rasonque in five weeks. More than 5,000 patients received a drug that doubled survival in second line pancreatic cancer, a disease where almost nothing has worked, and about 60% of the prescriptions came from community oncologists rather than academic centers.

AstraZeneca offered up to $134 a share for Rhythm Pharmaceuticals, about $10B. Rhythm sells Imcivree for rare genetic disorders where patients can’t regulate hunger. In March it was approved for people who gain severe weight after brain injury, usually following tumor surgery, and more than 700 patients have started on it since. AstraZeneca would run it through Alexion, its rare disease arm. Rhythm closed up 28%, so the market expects a deal without being certain of one.

Democrats took both chambers on Tuesday. Bernie Sanders is likely to chair the Senate health committee, which matters because the FDA user-fee law comes up for renewal and that’s the bill the agency depends on for most of its drug review budget. Analysts don’t expect a drug pricing fight right away. The Inflation Reduction Act already runs on its own, and the Most favored nation deals are signed. The nearer-term question is FDA commissioner nominee Heidi Overton, whose nomination could simply lapse, leaving the agency without a confirmed leader into next year. Separately, CVS said Wednesday it will split into two companies by 2028, with Aetna and Caremark on one side and its 9,000 retail pharmacies on the other. Arkansas and Tennessee have already banned common ownership of pharmacies and pharmacy benefit managers, and a bipartisan federal bill would do the same.

Novartis confirmed nine tumor reports among more than 6,000 children treated with Zolgensma since 2019. Zolgensma is a one time gene therapy for spinal muscular atrophy, a disease that used to kill most patients before their second birthday. Two of the nine showed the delivery vector had inserted itself into the patient’s DNA. The cases appeared 18 to 60 months after dosing, and families found out through their neurologists rather than any public notice.

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BIOTECH/PHARMA NEWS 🧬

🔹 Rasonque, approved August 26 for second-line metastatic pancreatic cancer, generated $197.6M in net revenue in roughly five weeks. More than 5,000 US patients were treated and about 2,700 prescribers wrote for it, about 40% academic and the rest community. TD Cowen called it “the best oncology drug launch in history,” and RBC now models $426M in Q4 and more than $3B in 2027. Pricing is the other story: $39,800 list for 30 days, above Keytruda, with plans covering more than 90% of patients paying claims. However, the quarter included a one time transfer of expanded access patients, many of them sicker and likely to stop sooner, so Q4 will be the first clean read. Revolution still lost $407.5M in the quarter and holds $3.7B in cash. A drug that doubled survival, approved in 35 days under a priority voucher, priced at a premium, but paid for anyway.

🔹 AstraZeneca made a non-binding offer of up to $134 per share including milestones for Rhythm Pharmaceuticals, about $10B. An earlier $124 per share approach came last month. Rhythm closed up 28% at $110.68, a market cap of about $7.64B, so the market is pricing a deal but not a certain one. Neither company commented. The asset is Imcivree (setmelanotide), which posted $92.1M in Q3 sales, up 29% from the prior quarter but below the $98.7M consensus. Since its March 19 approval in acquired hypothalamic obesity, which is weight gain following brain injury and often tumor surgery, Rhythm has collected more than 700 patient start forms. The deal would run through Alexion, AstraZeneca’s rare disease arm. It lands days after AstraZeneca unveiled a $1.5B annual cost savings program with a $2B one time charge, aimed at keeping its $80B 2030 revenue target alive. Rhythm doesn’t put AstraZeneca in the mass market obesity fight. It buys a rare disease launch with clear pricing power, which is a cleaner use of capital than the Bristol Myers merger talk from August.

🔹 Novo Nordisk’s Wegovy pill brought in DKK 5.39B, about $811M, in Q3 against consensus of DKK 4.96B. Novo raised its outlook to as much as 2% growth in sales and operating profit at constant currency, up from a forecast as low as a 4% decline in May. Lilly’s oral rival Foundayo did $184M, $44M short of estimates. Shares rose more than 6%, to just above $42, against more than $140 in June 2024. CFO Karsten Munk Knudsen is leaving and Galderma’s Luigi La Corte replaces him. The pill is the only obesity front Novo is currently winning. Lilly claims 63% of the US incretin market, retatrutide just beat Ozempic head to head, and semaglutide patents expire years before tirzepatide’s. One good quarter in oral doesn’t change that, but being first in a new format still counts for something.

🔹 Democrats regained the House and Senate on Tuesday. Sanders is likely to chair the Senate health committee and will have major sway over reauthorizing the FDA user-fee law, the industry’s must-pass bill. Analysts see limited drug pricing risk. Leerink says Democrats have “bigger fish to fry,” and RBC calls the IRA “too complicated to materially change.” The live risk is FDA commissioner nominee Heidi Overton. Her nomination may lapse, reopening the one FDA post still lacking a confirmed leader. The XBI has posted positive six-month returns after each of the last four midterms.

🔹 On Wednesday, CVS said it will split into two companies by the first half of 2028: Aetna and Caremark in one, its 9,000 retail pharmacies in the other. Arkansas and Tennessee have already passed laws barring common ownership of pharmacies and pharmacy benefit managers, and a bipartisan federal bill would do the same.

🔹 Novartis confirmed nine tumor reports among more than 6,000 patients treated with Zolgensma since 2019. Zolgensma is the one time gene therapy for spinal muscular atrophy, given mostly to infants. Two cases showed evidence of the AAV vector integrating into patient DNA, and seven have not been causally linked. Parents report the two confirmed cases arose 18 to 60 months after dosing. Families learned through their neurologists, and SMA Europe says regulators are assessing the evidence. The label already warns of a theoretical tumor risk from integration. What is new is that it’s no longer theoretical. Novartis ADRs slipped. The same day, reporting showed China’s investigator-initiated trial pipeline, the low cost proof of concept route behind many US licensing deals, slowing to a trickle after the patient deaths disclosed this summer. Since May 1, Order 818 confines new technology trials to top tier hospitals and carries million yuan fines. Both stories add cost and time to one time genetic medicines: years of follow up in the US, and slower early data out of China.

🔹 ASH abstracts posted Wednesday put four myeloma trispecific antibodies on the map. A trispecific grabs three targets at once, in this case a T cell plus two separate markers on the cancer, which is meant to stop tumors escaping by shedding a single antigen. J&J’s ramantamig hits CD3, BCMA and GPRC5D, the two myeloma targets of its already-approved Tecvayli and Talvey, in one molecule. Combined with Darzalex and Revlimid as induction in newly diagnosed, transplant-eligible patients, it produced minimal residual disease negativity, meaning no detectable myeloma cells, in all 20 patients evaluable after three cycles. AbbVie’s ABBV-2001 drew responses in 75 to 85% of relapsed or refractory patients, with 83 to 88% of complete responders MRD-negative. Innovent’s IBI3003 reached 77% at its Phase 2 dose, and Shanghai Xianxiang’s SIM0500 up to 86% at the highest doses. However, there were 20 patients is a cohort, it was not a trial, and ramantamig’s induction setting is where MRD negativity comes easiest. The open question is whether one trispecific beats two sequenced bispecifics, and none of this answers it. Two of the four are from China.

🔹 Sanofi stopped development of its Nurix-partnered oral STAT6 degrader for eczema. STAT6 sits downstream of IL-4 and IL-13, the targets of Dupixent, and protein degraders are the most credible route to hitting it in pill form. Sanofi told Leerink that “emerging nonclinical findings” didn’t warrant further work, but that STAT6 remains “an important pathway.” Nurix had collected $10M when phase 1 began in August and fell more than 40%. The distinction worth holding onto is molecule versus mechanism. A nonclinical finding specific to one compound says little about Kymera’s STAT6 degrader, whose mid-stage readout is due later this year, and Sanofi has said it has another STAT6 approach. But an oral Dupixent remains a hypothesis, and the first pharma-backed attempt at it is gone.

🔹 Amgen published a study of more than 544k adults comparing Repatha against ezetimibe, followed for up to four years. Among patients with a baseline LDL measurement, four year heart attack risk was 5.88% on Repatha versus 7.76% on ezetimibe, about 20% lower. It’s in the American Journal of Preventive Cardiology. The clinical question is: when a statin isn’t enough, what comes next? No randomized trial has ever compared the two head to head. But this is observational data with a careful design rather than a trial. Patients who get an expensive injectable differ from patients who get a cheap generic pill in ways you can only partly adjust for. Amgen ran it and Amgen announced it. The commercial timing explains more than the science does. Merck’s oral PCSK9 inhibitor Lipfendra launched in July at $315 a month, so Amgen now needs evidence that an injectable earns its slot ahead of ezetimibe and against a pill.

WATCHLIST 👀

• Capricor deramiocel: FDA decision Nov 22 in Duchenne, the next test of the agency’s second-chance posture on rare disease

• Vertex povetacicept: FDA decision Nov 30 in IgA nephropathy; a late-October citizen petition asks for mandatory antibody-level monitoring

• AstraZeneca / Rhythm: whether the reported approach becomes a signed deal, and at what premium to $110.68

• Treasury COINS Act rule: comments due Dec 7

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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: Revolution Medicines

Consistency is key to scale

As manufacturing becomes more distributed, standardization can help reduce batch-to-batch variation and support consistency.

Learn more

🎙️ 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 MERCH STORE.

Subscribe now

VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Good data and bad stock reactions kept coming together this week. Moderna’s personalized melanoma vaccine cut the risk of recurrence or death by 42% in a 1,137-patient Phase 3, and the stock fell nearly 25%. Alnylam beat on earnings, grew product revenue about 52%, and lost a quarter of its value in a day. In both cases the drug worked but what moved the stock was the gap between the result and what people had already assumed. Moderna had quadrupled since August on a topline with no numbers in it, and Alnylam’s heart trial got bigger for the second time in six months. Conversely, Genmab’s petosemtamab halved the risk of death in head and neck cancer and added more than $7B in market value.

Lilly had a great quarter. Q3 revenue rose 39% to $24.4B and guidance moved up $5.5B, the third raise this year. Volume grew 53% while realized prices fell 15%. A day earlier, retatrutide beat Ozempic on blood sugar and more than doubled its weight loss in a head-to-head diabetes trial. Lilly keeps winning because its numbers land above an already extreme consensus, which is harder than winning a trial.

The FDA published draft guidance that would let a gene editor approved for one mutation extend to other mutations in the same gene on laboratory data alone. Prime rose 15% and Beam 8%. Also, HHS told compounders it would not enforce against six unapproved peptides that FDA scientists had argued against. One policy builds a rigorous shortcut for medicines with real mechanisms. The other waives the evidence bar entirely for products with almost none.

Treasury’s China rule finally was published this week, and it’s narrower than feared on deals and broader than expected on equity. The proposed rule would bar US investment in Chinese companies developing small molecules, biologics, vaccines and cell and gene therapies, while leaving plain licensing largely intact. Gilead paid nearly $1.3B in cash for a Chinese oral IL-23 receptor peptide the same week, which is what the rule leaves alone.

And autoimmune cell therapy took two more hits. Artiva dropped its natural killer cell program after two patient deaths and cut 94% of staff. Bristol Myers disclosed a death in its multiple sclerosis CAR-T trial.

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BIOTECH/PHARMA NEWS 🧬

🔹 Lilly reported Q3 revenue of $24.4B, up 39% and roughly $2B above consensus. Mounjaro alone did $10.7B, up 65%, and Zepbound $5.3B, up 48%. Full year guidance moved to $91B to $92B from $85B to $87B, and shares rose about 6% to an all time high. The number underneath those numbers is the interesting one: volume grew 53% while realized prices fell 15%. Lilly is growing almost entirely on units, against a price environment that keeps getting worse. About $900M of the quarter came from one-off items, mostly $410M in Jardiance milestones with no further milestones remaining, plus favorable rebate adjustments. And adjusted earnings guidance landed at $35 to $36 per share, because acquired in process R&D charges from Q3 deals outweighed operating improvement. Lilly is spending its incretin windfall on pipeline as fast as it earns it. Separately, Lilly is merging its US and international divisions into “Lilly Global Markets” under Ilya Yuffa when Patrik Jonsson retires at year end. A company selling the same two molecules everywhere no longer needs two commercial organizations, and the structure is built for retatrutide’s launch.

🔹 Lilly’s retatrutide beat Ozempic in a head-to-head diabetes trial. In an open label, 80 week study of 1,298 adults on metformin, retatrutide lowered A1C by 2.2 points at both 9 mg and 12 mg versus 1.8 for Ozempic at 2 mg, from a baseline near 8.3%. Superiority was formal at 12 mg and nominal at 9 mg. Weight loss was 20.9% and 19.5% versus 9.4%. However, discontinuation for adverse events ran 7.9% and 4.8% versus 2.7%, with more diarrhea. Doubling the weight loss of the best known GLP-1 in diabetes, where weight loss is usually harder to achieve than in obesity, sets retatrutide up as Lilly’s next franchise rather than a high dose niche. Novo’s response was that Ozempic shouldn’t be judged on weight loss alone, pointing to its heart, kidney and liver outcomes data. Lilly plans to file in obesity in early 2027. Leerink models $15B in annual sales by 2032 against a $10B consensus.

🔹 Genmab’s petosemtamab, a bispecific antibody targeting both EGFR and LGR5, plus Keytruda cut the risk of death by 50% versus Keytruda alone at the first interim analysis in first line PD-L1-positive head and neck cancer. Hazard ratio 0.50 (95% CI 0.37-0.67, p<0.0001). Response also hit, with an odds ratio of 3.17 (2.06-4.89). Benefit held regardless of HPV status, which TD Cowen says supports a broad label, and there were no new safety signals. Genmab gained more than $7B in market value to above $35B. It bought the drug in an $8B takeover of Merus last year. What’s missing is all the other numbers, including median survival in each arm, absolute response rates, patient count and follow up duration. Worth noting an odds ratio of 3.17 does not mean three times the response rate, and a hazard ratio of 0.50 does not mean double the median survival. Those are different things and they get conflated constantly. Still, an overall survival win at the first look in a disease where Keytruda has been the frontline ceiling since 2019 is hard to argue with. Genmab now has a credible replacement for its Darzalex royalties before they roll off.

🔹 Merck and Moderna’s intismeran autogene plus Keytruda reduced recurrence or death by 42% versus Keytruda alone in resected high-risk melanoma: hazard ratio 0.58 (95% CI 0.45-0.75) at a median 24.6 months, with 24-month recurrence-free survival of 82.2% versus 70%. Distant metastasis-free survival had a hazard ratio of 0.62. The curves didn’t separate at all for the first six months, then diverged sharply, which is consistent with a vaccine that needs time to generate an immune response. Median time to first dose was 64 days. Discontinuation for adverse events was 7% versus 5%. Investors wanted 40 to 50%, Moderna had called 35% clinically significant, and the Phase 2 showed 44%. RBC called it “the low end” of expectations, and Moderna fell nearly 25% after a stock that had quadrupled since August. The data is clean and approval looks likely. But the two month manufacturing lag might be a bit problematic commercially.

🔹 Alnylam reported Q3 revenue of $1.46B including a one time $300M Roche milestone, with Amvuttra at $1.13B and transthyretin product revenue up 59%. The stock fell about 24%. Two things did it. Management said TTR sales will land at the low end of the $4.2B to $4.5B range, with US inventory and price as Q4 headwinds. The bigger problem was the Phase 3 trial for nucresiran, the next-gen version. Enrollment rose from about 1,750 to about 2,250 patients, after already rising from 1,250 in April, with the stated aim of preserving statistical power under conservative event rate estimates. Launch timing stays around 2030. In a trial measuring heart events, you need a certain number of events to occur before you can tell whether the drug helped. If patients on modern therapy are having fewer events than expected, that is good for patients and bad for trial math, because you need more patients or more time to prove anything. Alnylam may well be right about the reason. But a company asking for a bigger sample twice in six months is telling you its effect size estimate moved.

🔹 Treasury published its proposed COINS Act rule on Oct 26, with comments due December 7. It would prohibit US investment in Chinese companies developing or producing small molecules, biologics, vaccines, cell and gene therapies and their delivery technologies. Licensing a drug remains permitted, but equity taken by the licensor, NewCo structures, profit sharing collaborations and certain governance rights would all carry real risk. Those are precisely the structures the last two years of China deals have used. The industry is split over how far the licensing exemption actually reaches, and entry into force is likely close to the end of the first quarter of 2027. Meanwhile buyers kept buying. Gilead paid nearly $1.3B in cash for PepStar’s oral macrocyclic peptide against the IL-23 receptor, currently in Phase 1, the same target as Skyrizi and Tremfya. An all cash asset purchase with no equity attached is exactly what the rule leaves alone. Expect that to become the default template.

🔹 The FDA issued draft guidance for gene therapies that correct different mutations in the same gene. A sponsor would win a first approval for one mutation the conventional way and define what the agency calls an individualized feature space in that application. Later mutations falling inside that space could then be approved on laboratory data alone, without a new clinical study. This is the regulatory answer to Baby KJ Muldoon, the infant treated with a base editor in May 2025, where the manufacturing cost alone was $1.65M for one patient. Prime Medicine rose 15% and Beam 8%, and CMS plans to broaden its Medicaid access program for cell and gene therapies beyond sickle cell disease. This week HHS also said it will not enforce against compounders making six unapproved peptides, which a July advisory panel narrowly backed over FDA reviewers’ objections. None has been tested for safety and efficacy in clinical trials. Comments are open for two weeks. Worth saying that compounding sits outside the approval system entirely, so this isn’t a lowered standard in the way the gene editing guidance is a changed one. But it’s the same department in the same week, building a careful evidence framework in one place and declining to police a corner with no evidence in another.

🔹 Artiva discontinued AlloNK, its donor-derived natural killer cell therapy for rheumatoid arthritis and other autoimmune diseases, after two trial deaths. One patient developed a brain disorder that an investigator linked to fludarabine, the chemotherapy used to prepare patients before cell infusion. The other died suddenly about two months after treatment with no cause determined. Artiva says neither death appears related to its cells, but the FDA paused the Phase 2a, the Phase 3 stopped dosing, and the company cut 94% of staff to run a strategic review with $319.1M in cash. Days earlier, Bristol Myers disclosed that a patient in its multiple sclerosis trial of zola-cel died 44 days after infusion, after late-onset motor symptoms that didn’t respond to steroids, then septic pneumonia.

WATCHLIST 👀

• Capricor deramiocel: FDA decision Nov 22 in Duchenne, the next test of the agency’s second-chance posture on rare disease

• Vertex povetacicept: FDA decision Nov 30 in IgA nephropathy, with infection risk under scrutiny

• Treasury COINS Act rule: comments due Dec 7; watch whether the final text clarifies licensor equity and NewCo structures

• Genmab petosemtamab: full LiGeR-HN1 data including medians and absolute response rates at a future meeting

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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: https://onthepen.com/news/retatrutide-doubles-ozempic-weight

A new model for making genomic medicines

In vivo therapies could accelerate a shift towards new ways of manufacturing, scaling, and delivering genomic medicines.

Watch 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 MERCH STORE.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

The Moderna data leaked today, and the stock fell more than 25%. A publication broke the ESMO embargo two days before Saturday’s presentation, results started circulating on social media, and ESMO had to release them early. The number everyone had been waiting for: intismeran plus Keytruda cut the risk of recurrence or death by 42%, hazard ratio 0.58.

That number is fine. BMO called the melanoma data “clinically meaningful and likely approvable.” What fell apart was everything investors had attached to it. In August, Moderna announced this trial hit its endpoints with no hazard ratio, no p-value and no confidence interval, and gained 177% in a day, the largest single day move by any S&P 500 company this century. Eight days after that they raised $2 billion in convertible notes against the new price. With no number in the room, people priced a platform that works across cancers. The actual number tells you about melanoma and nothing about kidney, lung or bladder, where the other trials are still running. BMO’s warning was explicit: don’t extrapolate. Overall survival data isn’t available yet. Moderna is still up 525% on the year.

Two rare disease stocks jumped this week. Disc Medicine’s bitopertin treats a genetic disease that makes sunlight physically painful. The FDA rejected it in February because the company showed the drug lowered the toxic molecule causing the problem, but not that patients actually spent more time outside. On Monday a 183-patient Phase 3 showed both, and the stock rose more than 35%. On Thursday Biohaven said the FDA had accepted a resubmission for Vyglxia, a spinocerebellar ataxia drug it rejected last November, and will convene an advisory panel. Shares jumped about 25%. Neither company has an approval but investors are buying a change in who reviews the file and how, a week after the agency launched its Rare Disease Framework Initiative. If that holds, a lot of rejected rare disease drugs just got more valuable.

GSK got two FDA approvals in 48 hours, both ahead of schedule. Hibsago is the first drug that can get hepatitis B patients off lifelong antivirals, and about one in five reach that. It came six days early with a boxed warning attached. A day before that, Jemperli was approved for a type of rectal cancer where patients can now skip chemotherapy, radiation and surgery entirely.

Roche signed a deal worth up to $15B with Hansoh for preclinical antibody-drug conjugates, its sixth China deal since late August. In the same week, Treasury prepared a proposed rule that would screen US licensing deals with Chinese biotechs.

Three interesting readouts. Merck KGaA paid a 130% premium for Silence Therapeutics because its polycythemia vera drug is dosed every 12 weeks against a weekly competitor. Roivant’s brepocitinib cut treatment failure by about three quarters in two uveitis trials. AbbVie’s lutikizumab won in hidradenitis suppurativa by 8 points. All three disclosed numbers on day one.

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BIOTECH/PHARMA NEWS 🧬

🔹 Merck and Moderna's Phase 3 melanoma data was scheduled for the ESMO Presidential Symposium on Saturday. It leaked on Thursday instead, after a publication broke the embargo and the results started circulating on social media, forcing ESMO to release them early. Intismeran autogene plus Keytruda cut the risk of recurrence or death by 42%, hazard ratio 0.58, in patients with resected stage IIB-IV melanoma. Moderna fell more than 25%. Merck fell too. The data itself is good. BMO called it "clinically meaningful and likely approvable." What collapsed was everything investors had built on top of it. The August topline announced that the trial met both endpoints without releasing a hazard ratio, a p-value or a confidence interval, and Moderna gained 177% that day, the largest single session move by any S&P 500 company this century. Eight days later the company raised $2B in convertible notes against the new price. With no number available, the market priced a platform that works across tumor types. The number that arrived says something specific about melanoma and nothing about kidney, lung or bladder cancer, where the other trials are still enrolling. BMO's note was explicit about not extrapolating. Overall survival data isn't available yet. Moderna is still up 525% on the year.

🔹 The FDA approved GSK and Ionis’s Hibsago (bepirovirsen) on Oct. 20, six days ahead of its goal date, as the first antisense therapy for chronic hepatitis B. It had already been approved in Japan in August. It is for adults without cirrhosis, on nucleoside analogue antivirals for at least six months, with suppressed viral DNA and surface antigen at or below 3,000 IU/mL. In the pooled B-Well 1 and 2 trials, 19% of patients reached functional cure versus 0% on placebo, rising to 26% when surface antigen started at or below 1,000. Functional cure means virus and antigen undetectable for 24 weeks after all treatment stops, so patients can come off antivirals they’d otherwise take for life. The catch is monitoring. The drug carries a boxed warning, the FDA’s most serious category, covering liver enzyme flares and low platelets, with weekly or biweekly lab tests. Jefferies says that could slow uptake outside specialist centers, while still modelling about $3B at peak, a meaningful piece of GSK’s £40B 2031 revenue goal. The FDA also authorized a Roche test to select patients. Price is undisclosed pending payer talks. The number that will matter is how many eligible patients hepatologists actually screen in.

🔹 On Oct. 19 the FDA granted accelerated approval to GSK’s Jemperli (dostarlimab) as a treatment for stage 2 or 3 rectal cancer in patients whose tumors have mismatch repair deficiency or high microsatellite instability, a genetic signature that makes tumors unusually responsive to immunotherapy. This is the population from the 2022 Memorial Sloan Kettering study where every single patient’s tumor disappeared. In the 154-patient AZUR-1 trial, 68% had a sustained clinical complete response at 12 months by investigator review, but only 47% by independent central review, which was the primary objective. That 21-point gap between what treating physicians saw and what blinded reviewers saw is the soft spot in this dataset. There have been no recurrences among responders after a median of more than two years. Treatment is nine infusions over six months. Serious adverse reactions hit 20% and discontinuations 3%. Accelerated approval means a confirmatory trial still has to show the responses hold. But the goal it sets for this disease is organ preservation instead of surgery, which for rectal cancer means avoiding a permanent colostomy.

🔹 Roche agreed on Oct. 19 to pay $400M upfront and up to $15B in total for two preclinical antibody-drug conjugates from Hansoh, plus more against targets Roche gets to pick. That’s Roche’s sixth China deal since late August and its 11th since January 2025. The urgency shows up in the Q3 numbers. Sales grew 7% to CHF16.1B, which Jefferies called “cosmetically ahead,” and Xolair came in at CHF848M against a CHF972M forecast as Celltrion’s biosimilar launched in the US. Ocrevus, Tecentriq and Hemlibra all face copies by the early 2030s. Washington is moving the other way. Treasury is poised to propose a rule under the outbound investment law known as the COINS Act that would add scrutiny to US licensing deals with Chinese biotechs. Earlier reporting suggested most deals would survive, with pathogen and military use technology excluded. China ran 81 licensing deals worth up to $110B in the first half of this year. A screen may slow that, but likely not stop it.

🔹 Merck KGaA will buy Silence Therapeutics for $20 a share in cash, about $1.3B, a 130% premium to the October 16 close. The asset is divesiran, a short interfering RNA that silences a gene called TMPRSS6 to raise hepcidin, the hormone that limits how much iron reaches the bone marrow. In polycythemia vera, where the body makes too many red blood cells, restricting iron slows that production. The Phase 2 numbers explain the premium: an 88% responder rate versus 19% on placebo, and patients needed an average of 0.2 blood draws over 36 weeks against 2.1 on placebo. Takeda and Protagonist’s Mimrylo, approved in August, works on the same hormone but is a weekly self-administered injection. Divesiran is dosed every 12 weeks. That’s the whole commercial argument. Merck KGaA is paying for a Phase 3 it still has to fund, and Silence shareholders were facing dilution or a sale, so they took the sale. Close is expected in Q1 of 2027.

🔹 Biohaven said on October 22 that the FDA accepted its resubmission for Vyglxia (troriluzole) in spinocerebellar ataxia and will hold an advisory committee, with a decision expected in Q1 of 2027. The agency rejected the drug last November, finding the key study unconvincing partly on design grounds, even though the data pointed to as much as 70% slower progression. Biohaven also withdrew its European application after evaluators questioned the evidence. The resubmission adds “new positive supportive analyses” but no new trial, which is the important detail. Disc Medicine ran the Phase 3 the FDA asked for. Biohaven is testing whether the same evidence reads differently under new leadership. TD Cowen said the panel “substantially increases the probability of approval.” RBC said it depends on how far the flexibility goes. The stock rose about 25%. An advisory panel cuts both ways, though. An outside committee can say no in public, and this FDA has overruled panels in both directions this year.

🔹 Disc Medicine’s bitopertin hit both primary endpoints in a Phase 3 trial in erythropoietic protoporphyria, a genetic disease where a toxic molecule builds up in red blood cells and causes burning pain when patients are exposed to sunlight. The trial randomized 183 patients aged 12 and up to the oral drug or placebo for six months. Protoporphyrin IX, the molecule causing the problem, fell 41.4% versus placebo (p<0.0001), and pain-free time in sunlight rose 12.2 hours a month at month six (p=0.001). That combination is exactly what the FDA said was missing when it rejected the accelerated filing in February. The agency wanted the biomarker and the actual patient benefit shown in the same trial. Dizziness hit 50% of patients, mostly mild and transient with nothing above grade 3, though that deserves attention in a pill people would take daily for life. Bitopertin has an unusual history: it failed in schizophrenia under Roche before Disc picked it up and moved it into blood disorders. Disc plans to resubmit by year end and raised $450M at $75 a share off the news. Jefferies sizes the market at $1B to $2B, and the only approved alternative, Scenesse, is an implant.

🔹 Two placebo-controlled Phase 3 trials of Roivant’s brepocitinib, an oral JAK1 and TYK2 inhibitor, both hit hard in non-infectious uveitis, an inflammatory eye disease that can cause blindness. Hazard ratio for treatment failure from week 6 to 48 was 0.27 in one trial (n=166) and 0.22 in the other (n=204), both p<0.0001. Cumulative failure at week 48 was about a third on drug versus roughly 78% on placebo. Pooled, 62% reached steroid-free disease control at 48 weeks versus 20%. Every secondary endpoint hit. Humira is currently the only approved non-steroid systemic option, so a pill competing against an injection given in an eye clinic is an easy pitch. The trials didn’t test Humira head to head, so any “better than Humira” claim is cross-trial inference. Stifel called brepocitinib “best-in-disease” and Cantor puts uveitis at about $5B peak. The drug was already approved as Lisraya in dermatomyositis in August. Filing for uveitis is planned for the first half of 2027. Safety detail wasn’t in the topline, and for a JAK inhibitor that’s the next thing to read.

🔹 AbbVie’s lutikizumab, an antibody that blocks both IL-1α and IL-1β, met its primary endpoint in 1,400 patients with hidradenitis suppurativa, a painful skin disease that causes recurring abscesses and tunnels under the skin. At week 16, 31.4% hit the main response measure versus 23.4% on placebo (p≤0.001), with eight ranked secondary endpoints also hitting, including meaningful pain reduction at week 8. No new safety concerns. An 8-point gap is real but modest, and the 23.4% placebo rate is high, which is common in this disease. UCB’s Bimzelx and Novartis’s Cosentyx already compete here, and AbbVie’s own Humira still anchors the category. The case for lutikizumab is a new mechanism for patients who stop responding to IL-17 drugs, which IL-1 biology supports in theory but which needs subgroup data from the full 36-week readout to confirm. AbbVie plans to file next year. Shares barely moved, down 0.6%. Investors heard a positive trial, not a new franchise.

WATCHLIST 👀

• Merck/Moderna intismeran: full INTerpath-001 Phase 3 melanoma data (n=1,137) at the ESMO Presidential Symposium on October 24. The August topline had no hazard ratio and moved the stock 177% in a day, so this is the big one.

• Treasury China biotech rule: proposed rule under the COINS Act expected as early as Oct. 23. Watch the scope on licensing, equity and NewCo structures.

• FDA Rare Disease Framework: public meeting Oct 28 at White Oak. Disc and Biohaven are the live test cases for how far the flexibility actually goes.

• Capricor deramiocel: FDA decision Nov 22 in Duchenne.

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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

Less complexity. More possibility.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Last month I reported four Phase 3 wins that arrived without effect sizes (This Week in Biotech #119), and said the numbers would show up eventually at medical meetings. Merck’s remigromig was the first, and it explains why they were held back. In 984 patients with diabetic macular edema, remigromig gained 9.1 and 8.7 letters of vision against 11.8 for Lucentis, a drug that has been on the market since 2006. Rates of the worst form of diabetic eye disease were about seven times higher, and treatment discontinuations about five times higher. So the trial cleared its bar (showed noninferiority), but it did it with worse safety than a drug that has been available for twenty years. Moderna’s melanoma vaccine is next up. The August topline had no hazard ratio either, and the stock gained 177% in a day on it. Full data at ESMO next Friday (Oct 24).

Bristol Myers did the same thing this week, and in their case the missing numbers matter more. Admilparant hit its Phase 3 endpoint in idiopathic pulmonary fibrosis at 60 mg and missed at 120 mg, with no effect size disclosed for either. A lower dose working better than a higher one is the result that raises the most questions, and without the numbers nobody can tell whether the 60 mg result is real.

On Wednesday, the FDA launched a Rare Disease Framework Initiative meant to make approvals “more predicatble,” and then expanded ImmunityBio’s Anktiva label almost three months early. It did that without a dedicated efficacy analysis in the new population, a year after refusing even to review the filing. The reasoning was that the two tumor types are similar enough that the original evidence carries over, which is defensible but it still means approving a drug for patients it wasn't tested in. Public meeting on the framework is October 28, with recommendations reportedly targeted for February.

OrbiMed closed $3B in new funds, OMass raised $310M privately, and Verastem raised $250M on the same morning as its pancreatic cancer data. Iambic got its AI designed pipeline public at $16 a share, the year’s 25th biotech IPO. Meanwhile two AI discovery partnerships came with small ish upfront payments. Zealand put $30M down on Generate Biomedicines and AstraZeneca $40M on insitro.

There were also a few late stage failures this week. BioNTech’s mRNA immunotherapy BNT113 failed to delay progression in head and neck cancer at an interim look and shares fell about 6%. Vanda’s social anxiety drug missed its Phase 3, 65.6 versus 66.0 on the distress scale, p=0.89. Syndax’s Niktimvo failed in idiopathic pulmonary fibrosis.

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BIOTECH/PHARMA NEWS 🧬

🔹 Full one year data for Merck’s remigromig came out at the American Academy of Ophthalmology meeting on October 10. Diabetic macular edema is swelling in the retina that causes vision loss in people with diabetes, and the standard treatments all block a protein called VEGF that drives abnormal blood vessel growth. Remigromig works through a different pathway entirely, which is why Merck paid $1.3B upfront for Eyebiotech in 2024 to get it. The trial randomized 984 patients to remigromig 0.5 mg, 0.8 mg, or Lucentis 0.5 mg, all dosed monthly. Vision gains were +9.1 letters (95% CI 8.1-10.1) and +8.7 letters (7.7-9.8) versus +11.8 (10.7-12.8) for Lucentis. Both doses were noninferior, which is what the trial was designed to show, and no secondary endpoint showed superiority. The safety signal is the bigger problem. Proliferative diabetic retinopathy, the advanced stage of diabetic eye disease, occurred in 6.7% and 6.1% of remigromig patients versus 0.9% on Lucentis. Adverse events led 4.9% and 4.5% to stop treatment versus 0.9%. Merck’s hypothesis is that the drug repairs the blood-retinal barrier rather than suppressing vessel growth, so the higher retinopathy rate may reflect the natural course of the disease rather than drug harm. BMO now sees “limited competitive potential.” The BAROLO trial and year two flexible dosing are what remain. The real case for a new mechanism rests on the 30 to 40% of patients who respond poorly to VEGF blockers, and this trial didn’t test them.

🔹 Bristol Myers Squibb’s admilparant met its Phase 3 primary endpoint in idiopathic pulmonary fibrosis at the 60 mg dose and missed significance at 120 mg. About 1255 adults were randomized 1:1:1 to 60 mg twice daily, 120 mg twice daily, or placebo for at least 52 weeks, with the endpoint being absolute change in forced vital capacity, a measure of how much air a patient can exhale. No effect sizes, confidence intervals or p-values were disclosed for either dose. Discontinuations for side effects were low and similar to placebo. The basic expectation in a dose ranging trial is that more drug means more effect, so when the lower dose works and the higher one doesn’t, the obvious question is whether the 60 mg result is real or came out of the noise. There are several possible explanations, like more side effects at the higher dose causing patients to drop out, but you’d need the actual numbers to tell. Phase 2 had shown a 62% slowing of decline at 60 mg over 26 weeks, which set a high bar. BMS fell 2.6%. Contineum, which has a lower dose drug against the same receptor in Phase 2, fell roughly 25 to 36% the same day. The liver injury risk flagged in an earlier protocol amendment isn’t addressed in the topline at all. ALOFT-PPF, in other progressive fibrotic lung disease, reads out in early 2027.

🔹 The FDA launched the Rare Disease Framework Initiative on October 14. The idea is to write down standards for rare disease drug development that account for how small these patient populations actually are, covering the whole path from the first meeting with the agency through whatever a company has to keep studying after approval. There’s a public meeting at White Oak on October 28 and recommendations are reportedly targeted for February, though the agency set no timeline itself. Leerink’s Joseph Schwartz said that the FDA “is not lowering the bar” but may be making the path “less of a guessing game.” The same day showed what that might look like. The FDA expanded Anktiva from ImmunityBio to cover papillary-only bladder cancer in patients who’ve stopped responding to BCG, the standard first line treatment. The decision came nearly three months early. The agency didn’t ask for a separate randomized trial. It extended the evidence from the 2024 approval in a different tumor type, reasoning that the two co-occur and are hard to tell apart. In May 2025 the agency refused to even file the application. That’s a defensible scientific argument, and it also means approving a drug for patients it wasn’t tested in. I think we can expect other companies to point to this the next time they want an approval without running the trial.

🔹 Two weeks after a Delaware court found that Yutrepia infringed a United Therapeutics patent, which sent Liquidia down almost 50% and United up about 13% in a day, the companies settled. That covers three patent suits, the antitrust claims and a North Carolina trade-secret case. Liquidia pays a net $380.7M in installments through April 2027 and keeps selling Yutrepia, its inhaled treprostinil, for pulmonary arterial hypertension. But Liquidia has to ask the FDA to remove pulmonary hypertension tied to interstitial lung disease from the label and stop promoting it there, which is the growth market where United’s Tyvaso holds the lead. Liquidia shares rose about 42% mainly because the math works for them: Yutrepia did a preliminary $222.7M in Q3 net sales and Liquidia holds $396.1M in cash, so the company is paying a little over one quarter of revenue to remove the risk of an injunction shutting it down entirely. United gives up a litigation option and keeps its most valuable market. Neither company won outright, and both can now plan their businesses.

🔹 Verastem’s oral KRAS G12D inhibitor VS-7375, which binds both the active and inactive forms of the protein, produced response rates of 36 to 50% in metastatic pancreatic cancer depending on how many prior treatments patients had received, 33% in colorectal and 43% in lung cancer. In 22 pancreatic patients at 900 mg, 6 month progression-free survival was 67%. The lung response rate came from 23 patients at 600 mg. These are small single arm cohorts, so the confidence intervals are wide. The competitive frame is Revolution Medicines, whose Rasonque was approved in August and nearly doubled survival in G12-mutant pancreatic cancer, though FDA documents suggest its effect is more modest in G12D specifically, and RevMed has a G12D-selective drug coming. RBC called Verastem’s profile “competitive.” Verastem has FDA alignment for a first line pancreatic Phase 3 starting by year-end, with colorectal and lung to follow in the first half of 2027. Shares rose about 18 to 20%, and the company raised $250M the same morning alongside announcing a CEO transition.

🔹 Arrowhead gave subcutaneous injections of an RNA interference drug that silences the tau gene to about 64 healthy volunteers. At day 105, tau fell 40% at the lowest dose tested, 69% at the middle dose, and an average of 73% at the highest, with individual reductions up to 85%. Side effects were mild: injection-site reactions, bruising, respiratory infections, headaches. The novelty here is the delivery rather than the target. This is a shot under the skin that reaches neurons behind the blood-brain barrier, where competitors have relied on spinal injections or engineered antibody shuttles to get there. Stifel called it “compelling” while noting tau is not yet a validated Alzheimer’s target and Biogen’s spinal injection tau drug has struggled. These are healthy volunteers, so this is a delivery result, not an efficacy one. Still early and still small, but it keeps alive the idea that the brain can be reached with an ordinary injection. Mild Alzheimer’s patients enroll next, with frontotemporal dementia and progressive supranuclear palsy trials planned.

🔹 OrbiMed raised $3B across two funds, including over $1B for Asia, a week after Forbion’s $2.6B close. Oxford-based OMass raised $310M, among the largest UK private biotech rounds in years, to compete in congenital adrenal hyperplasia against Neurocrine and Vertex’s Crinetics. Ultragenyx sold its second priority review voucher in a month, for about $203M after $210M for the first. On the deal side, Zealand Pharma agreed to pay Generate Biomedicines $30M upfront plus up to $35M in early milestones for AI-designed multispecific proteins in obesity, with nearly $1.2B in later milestones. AstraZeneca put $40M upfront into an insitro discovery deal. Gilead paid Vir $135M upfront and near-term with up to $1.74B more for three masked T cell engagers in solid tumors, a deal built on protein engineering rather than AI. And Iambic priced its IPO at $16 to raise $150M and rose about 13% on day one, the 25th biotech to go public this year. Worth noting Iambic had a molecule already in the clinic, IAM1363, an oral inhibitor of the HER2 growth receptor with Phase 1 activity in heavily pretreated patients, which most AI discovery companies going public don’t.

WATCHLIST 👀

• Merck/Moderna intismeran: full INTerpath-001 Phase 3 melanoma data (n=1137) at the ESMO Presidential Symposium on Oct 24. The August topline gave no hazard ratio, so this is the second of September’s no number wins to face a full dataset. Remigromig went first and didn’t survive the check.

• GSK/Ionis bepirovirsen: FDA decision in hepatitis B on Oct 26. A functional cure delivered by an antisense drug would be the first of its kind.

• FDA Rare Disease Framework: public meeting Oct 28 at White Oak, with recommendations reportedly targeted for February. The Anktiva decision this week is the preview of what the standard might look like in practice.

• Capricor deramiocel: FDA decision Nov 22 in Duchenne, on the refiled upper limb indication after July’s 9-3 negative advisory vote.

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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: mediamice . com (Article: Merck’s Remigromig Meets Primary Endpoint in Phase IIb/III DME Trial)

🎙️ 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 MERCH STORE.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Vaxcyte had the cleanest result of the week and also the most fully disclosed. Its 31-strain pneumococcal vaccine matched Pfizer’s Prevnar 20 and Merck’s Capvaxive on every strain the three vaccines share, and covers four additional strains neither competitor includes. Vaxcyte published the whole breakdown, including the two strains that only cleared the older and looser statistical bar. The stock rose about 31% and the company raised $1B within hours.

Viatris paid $1.65B for Pacira, whose lead drug starts losing exclusivity in about three years. Shionogi paid $2B for IntraBio, which sold $67.9M of product last year. Ultragenyx sold a priority review voucher, essentially a transferable coupon that lets the buyer get a faster FDA review on any drug they choose, for $210M. Meanwhile Caribou’s allogeneic CAR-T cell therapy, made from donor cells rather than the patient’s own, had FDA clearance to enter Phase 3 but couldn’t find anyone willing to fund the trial, and is shutting down research. There are seven approved CAR-T therapies and all seven use the patient’s own cells. After more than a decade and billions of dollars, no allogeneic (off-the-shelf) version has ever been approved, because the patient’s immune system clears the donor cells before they finish working. Investors were being asked to fund the next attempt at a problem nobody has solved yet.

Dutch court blocked Merck’s “under the skin” Keytruda in eight European countries on a Halozyme patent. Merck chose not to license the technology that Bristol Myers Squibb and Roche did license, and it’s now paying for that in the exact market where subcutaneous dosing was supposed to slow the Keytruda patent cliff.

Two readouts set the tone in oncology. AbbVie and Genmab’s Epkinly cut progression or death risk by 51% in newly diagnosed diffuse large B-cell lymphoma, above the roughly 40% the Street wanted. ArriVent lost more than half its value when furmonertinib missed its primary endpoint with a p-value of 0.0654.

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BIOTECH/PHARMA NEWS 🧬

🔹 Vaxcyte’s OPUS-1 trial dosed 4,047 people across about 30 US sites. Pneumococcal disease causes pneumonia, meningitis and bloodstream infections, mostly in older adults, and current adult vaccines cover 20 or 21 strains, but Vaxcyte’s VAX-31 covers 31. In 3,572 adults aged 50 and older, randomized evenly to VAX-31, Pfizer’s Prevnar 20 or Merck’s Capvaxive, the vaccine matched both competitors on all 28 strains they have in common, and generated a strong enough immune response against four strains the others don’t contain to clear the trial’s superiority threshold. Strain by strain, VAX-31 cleared the bar on all 20 comparisons against Prevnar 20 and 17 of 19 against Capvaxive. Two strains, 3 and 12F, cleared only the older and looser statistical threshold rather than the stricter one, and Vaxcyte disclosed that rather than leaving it out. No vaccine-related serious adverse events, no discontinuations. The company estimates VAX-31 covers 13 to 36% more invasive pneumococcal disease than current adult vaccines. The worry going in was dilution. Each strain in a pneumococcal vaccine has to be attached to a carrier protein, and the more strains you add, the more the immune response to each one can weaken. That’s the reason nobody had gone past 21, but it didn’t happen here. Shares rose about 31%, then gave back about 10% when the company priced $474M of stock at $64 plus $500M of convertible notes. OPUS-2 and OPUS-3 read out in the first half of 2027 and the license application is planned for the first half of 2028, which leaves Pfizer and Merck a long runway to respond.

🔹 An independent monitoring committee recommended stopping argenx’s UNITY trial for futility after an interim analysis concluded the study couldn’t hit its primary endpoint in Sjögren’s disease, an autoimmune condition that attacks the glands producing tears and saliva. The interim reportedly covered more than 500 of 630 enrolled patients. No effect size was disclosed. Results hadn’t been expected until the second half of 2027, and analysts had pegged Sjögren’s at up to $1.4B peak. Shares fell about 15%. What makes this notable is that Novartis and Amgen have both now won Phase 3 trials in the same disease with different mechanisms, which suggests the problem is Vyvgart’s target rather than the indication. Vyvgart works by blocking the neonatal Fc receptor, which clears disease-causing antibodies from the body, and that mechanism has carried argenx across myasthenia gravis and CIDP. The same morning, FB102, a CD122 antibody from argenx’s $2.2B Forte acquisition, met its Phase 2 primary endpoint in 126 adults, protecting the intestinal lining through an eight-week gluten challenge at p=0.0176. No magnitude given and phase 3 is planned.

🔹 A Dutch court ordered Merck to stop making and selling Keytruda Qlex, its under-the-skin version of pembrolizumab, in eight European countries after finding it infringed a Halozyme patent on rapid subcutaneous delivery of large biologics. It follows a German preliminary injunction in December 2025 and runs alongside a US suit in New Jersey asserting 15 patents. The strategic point is the licensing decision. Bristol Myers Squibb and Roche licensed Halozyme’s enzyme for subcutaneous Opdivo and Tecentriq. Merck built its own and now faces injunctions market by market. Subcutaneous Keytruda is Merck’s main tool for moving patients onto a format that outlasts the intravenous patents, which start expiring in 2028, so every month blocked in Europe is a month of switching lost. Merck shares barely moved, and the intravenous product is unaffected.

🔹 Caribou is halting research and exploring strategic alternatives after failing to finance a Phase 3 of vispa-cel, its donor-derived CAR-T therapy for lymphoma, despite having FDA agreement on the trial design. Leerink’s Daina Graybosch said that investors “were unwilling to fund the trial.” Its myeloma program stops too. Shares fell about 25% to under $1, down from above $30 in 2021, and the company is now a reverse merger candidate. Allogeneic CAR-T means using cells from a healthy donor instead of the patient’s own. The problem has always been that the patient’s immune system recognizes those donor cells as foreign and clears them, often before they’ve finished killing the cancer. Companies have tried to get around it by knocking out genes on the donor cells and wiping out more of the patient’s immune system first, and it still hasn’t fully worked. Caribou didn’t say why investors passed, but a Phase 3 ready asset failing to raise in a week when Forbion closed $2.6B tells you something about appetite for this modality.

🔹 Viatris will pay $36.50 per share in cash, a 45% premium, for Pacira, closing by end of 2026. Pacira sells Exparel for post-surgical pain and Zilretto for knee osteoarthritis, which together did $692M in 2025, up only about 4%. What Viatris is really buying is a cash stream with a known expiry date. Settlements already let Fresenius Kabi and a Hengrui subsidiary sell a small share of US Exparel volume, rising toward 30% within three years, and broader generic erosion is expected from 2030. Zilretto’s patents run out in 2031. That timeline would scare off most branded acquirers, but Viatris is a generics company. Managing declining products and squeezing value out of expiring patents is the business they’re in. Leerink calls the deal immediately accretive while expecting no change in near term trajectory.

🔹 AbbVie and Genmab added their drug Epkinly to standard chemotherapy in newly diagnosed diffuse large B cell lymphoma, and it cut the risk of progression or death by 51%. Epkinly is a bispecific antibody, meaning it physically grabs a cancer cell with one arm and one of the patient's own T cells with the other, forcing the immune system to attack. The trial enrolled about 900 patients at intermediate or high risk, randomized 2:1 to six cycles of standard R-CHOP chemotherapy with Epkinly or with placebo. Hazard ratio was 0.49 in both the primary higher-risk group and the broader population. Analysts had modeled about 40%. Safety matched what was already known. This is the first bispecific to win a Phase 3 in newly diagnosed lymphoma, which matters because that's where doctors are actually trying to cure people rather than extend survival, and it's the largest patient group. TD Cowen called it the "undisputed standard," though worth noting the trial didn't test against Roche's Polivy, so that comparison is cross-trial inference rather than a head-to-head result. Genmab rose as much as 14%. Epkinly did $312M in the first half and TD Cowen sees $3B eventually. Overall survival data and filing timing haven’t been disclosed.

🔹 ArriVent's furmonertinib missed its primary endpoint in newly diagnosed lung cancer and the stock fell more than 50%. The trial enrolled 398 patients whose tumors carry a specific mutation called an EGFR exon 20 insertion, which shows up in a small slice of non small cell lung cancer and responds poorly to the standard targeted drugs. Patients got either furmonertinib as a once daily pill or chemotherapy. The drug delayed progression by 1.5 months, 11 versus 9.5, with a hazard ratio of 0.75. The p-value was 0.0654, just above the 0.05 threshold. Jefferies had wanted a three month gap. Response rates and investigator-assessed progression both favored the drug and survival data is still immature, but none of that rescues a missed primary endpoint. The competitive position makes it worse. J&J’s Rybrevant is already on the market, and Taiho and Cullinan have started a filing for their own drug in the same setting. An oral pill that lets patients skip chemotherapy would have been a real advantage. At 0.75 without significance, it’s a hypothesis.

WATCHLIST 👀

• Merck remigromig: full first year Brunello data in diabetic macular edema on October 10, the first of September’s no-number Phase 3 wins to show its numbers

• GSK/Ionis bepirovirsen: FDA decision in hepatitis B on October 26

• Capricor deramiocel: FDA decision November 22 in Duchenne

• PhRMA v. Kennedy: whether PhRMA moves for a preliminary injunction before GLOBE’s January 1 start

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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: STAT News

🎙️ 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 MERCH STORE.

Subscribe now

THIS WEEK’S KEY TAKEAWAYS 🔑

The three biggest checks written this week were all for options rather than assets. AstraZeneca invested $2 billion into Summit without buying ivonescimab, the drug everyone assumed it wanted. Back in July 2025 the rumored price for a full license was $15 billion. Instead AstraZeneca took an equity stake and the right to run combination trials. Sanofi paid Regeneron $1 billion upfront for four antibodies, only one of which has ever been tested in a person. And Novo paid Hengrui $300 million for an obesity pill that has never been dosed in a human at all. In every case the underlying biology is already proven, so these companies are buying is a position rather than a drug, which is a lot cheaper than a full license or an acquisition.

Same thing as last week (and several weeks before): Withhold thy data and be rewarded, publish and be punished. uniQure published four year Huntington’s data with all the numbers attached, and its primary endpoint lost statistical significance as patients dropped out of the comparison group. The stock fell about 40%. Kodiak Sciences announced that two wet macular degeneration drugs were noninferior to Eylea without publishing a single letter of visual acuity, and it jumped 62% premarket.

On the policy side, the administration’s drug pricing program came out much smaller than proposed. CMS finalized GLOBE, which ties Medicare payments for office-administered drugs to prices in 19 other countries, then wrote in waivers for any company already in a voluntary pricing agreement. Projected savings fell 96%, from $11.9 billion to about $440 million, and the number of manufacturers affected dropped from 19 to 4.

And lastly, Lilly’s amylin + tirzepatide combo hit 23.3% weight loss in patients with type 2 diabetes, who typically lose considerably less weight on these drugs than people without diabetes. Every competitor presenting at the European diabetes meeting in Milan landed between 10% and 13%.

No video today, I’m not feeling well. Thanks for reading Biotech Blueprint, and I’ll be back next week with more news from biotech and pharma.

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BIOTECH/PHARMA NEWS 🧬

🔹 AstraZeneca is investing $2B in Summit without buying the drug. The money goes into convertible preferred stock priced at an effective $18.36 per common share, a 10% premium to where Summit had been trading. Summit keeps full ownership of ivonescimab. AstraZeneca gets a stake in the company plus the right to run combination trials. AstraZeneca will sponsor trials combining Summit’s ivonescimab, a PD-1/VEGF bispecific, with sonesitatug vedotin, its own Claudin 18.2 antibody drug conjugate, in gastric and biliary tract cancers, with costs shared. A non-binding memorandum covers more combinations with AstraZeneca’s antibody drug conjugates in lung, breast and gastrointestinal cancers. Summit rose from $15.48 to $18.51 premarket, up 19.6%, and originator Akeso gained 15.5% in Hong Kong. Summit’s US case still rests on global HARMONi overall survival data due in 2028, after China-only results the market has learned to discount. AstraZeneca got equity exposure and combination data without paying for a license. If HARMONi works, it owns a stake and the trial results, and if it doesn’t, it owns preferred stock.

🔹 Sanofi will pay Regeneron $1B upfront and up to $7B in milestones for four long-acting antibodies targeting IL-13, IL-4 or the IL-4 receptor, which is the same biology behind Dupixent. Costs and profits split 50/50, Regeneron leads R&D, Sanofi commercializes. The lead candidate is in an early eczema trial and the other three enter human testing in 2027. Dupixent sold $10.9B in the first half of 2026 and its key patents expire over the next five years, though the companies argue a patent thicket could stretch protection to 2045. The logic is lifecycle management: a longer-acting version of the same mechanism is the cleanest way to move patients onto a new drug before biosimilars arrive. The weakness is that nothing in the package yet demonstrates a dosing advantage, and RBC’s Brian Abrahams called the drugs “very early.” Regeneron fell 3.1% on a deal that pays it $1B, which tells you investors read this as Sanofi worrying about the patent cliff rather than as a vote of confidence in the new molecules.

🔹 Novo licensed HRS-1596 from Hengrui, a once weekly oral GLP-1/GIP dual agonist, for $300M upfront and up to $2.6B in total, taking rights outside China, Taiwan and nearby markets. The drug is described as “Phase 1 ready,” meaning no human data exists. Novo is betting on weekly dosing. A weekly pill would combine Wegovy’s schedule with an oral format and compete directly with Zepbound’s mechanism. The deal landed a week after a capital markets day where Novo guided growth only “broadly in line with industry peers” and the stock fell about 5%. Novo also picked up obesity assets from Kallyope, which rebranded as TriGemX Bio with $94M for migraine. Novo is buying the next gen lane it failed to build internally, and the Chinese pipeline is again the cheapest place to buy it, in a year when Chinese-designed drugs make up roughly half the global pipeline.

🔹 CMS finalized a program called GLOBE, which ties what Medicare pays for certain drugs to what those same drugs cost in 19 other countries. It covers Part B, meaning drugs administered in a doctor’s office or hospital rather than picked up at a pharmacy, and it starts Jan 2027 in regions covering about 25% of Medicare beneficiaries. The original proposal projected $11.9B in savings over seven years. The final rule projects $440M, which is a 96% cut. The reason is the waivers. Any manufacturer already in a voluntary pricing agreement with the administration gets exempted, which drops the number of companies subject to the rule from roughly 19 to 4. Orphan drugs, plasma products, some cell and gene therapies, and biologics already facing biosimilar competition are excluded too. So the most favored nation deals companies signed in August and September turn out to have been the price of buying out of this, which makes those deals look even better for the companies than they did at the time.

🔹 Beam sued YolTech Therapeutics, its U.S. licensee Serapha Bio, CEO Yuxuan Wu and former Beam scientist Zi Jun Wang in Massachusetts federal court on September 25. The complaint alleges Wang founded YolTech while still employed at Beam and accessed dozens of records outside her area, “including at night and on weekends,” then filed patents five months after leaving. The disputed asset, SERP-01, edits the same nucleotide at the same location as Beam’s clinical stage BEAM-302 in alpha-1 antitrypsin deficiency, a genetic disorder that causes lung and liver damage. Serapha, backed by $230M from RA Capital and RTW for a reverse merger listing, plans a Phase 2/3 trial in late 2026 or early 2027 and “categorically refutes” the claims.

🔹 uniQure published four year data on AMT-130 in Huntington’s disease, and the signal weakened. At 48 months, the 12 high dose patients showed 44% slowing on the prespecified composite disease rating scale versus matched external controls, with p=0.144, which is not statistically significant. Total Functional Capacity slowed 61% with a nominal p of 0.008, and analyses adjusted for missing data gave 54% and 68%. For comparison, at 36 months 15 patients had shown 80% slowing on the composite scale. So the effect looks smaller the longer the follow up runs. The bigger problem is that the external control group has 53% missing data at 48 months, and the FDA had already called the comparator distorted when it asked for a sham-controlled trial. Five high dose patients experienced treatment-related serious central nervous system inflammation, all of which resolved. Shares fell about 40% at the open to just under $24, roughly $1B of value. The September accelerated approval application now has a decision due in about 8 months, and the durability question has become a statistics question.

🔹 Kodiak Sciences reported that two of its eye drugs matched Eylea, the current standard treatment for wet age-related macular degeneration, in a trial of about 690 patients who hadn't been treated before. Both hit the one year primary endpoint on visual acuity. Eylea requires injections directly into the eye every one to two months, so dosing interval is the real commercial question, and 54% of Zenkuda patients stretched to six months between doses. Intraocular inflammation, the complication that hurt earlier long-acting competitors, ran 0% and 0.4%. What Kodiak did not disclose is letter gains for any arm, or the noninferiority margin. That omission matters for a company whose earlier drug failed this exact comparison against Eylea and lost about 80% of its value. Combined with the GLOW2 diabetic retinopathy win in March, Kodiak plans a single Q4 2026 application covering wet AMD, diabetic retinopathy and retinal vein occlusion. The stock was up 62% premarket at $52.44. Clean safety signal, but the vision numbers remain unpublished.

🔹 Lilly combined tirzepatide with eloralintide, an amylin analog. Amylin is a hormone that works alongside insulin to signal fullness. In 367 adults with obesity and type 2 diabetes over 48 weeks, the combination produced 23.3% weight loss, about 54 pounds, versus 14.8% on tirzepatide alone and 3.0% on placebo. A1C fell 2.9 points from a baseline of 8.1%, compared with 2.4 on tirzepatide. Eloralintide on its own peaked at 12.3%. What makes 23.3% striking is the population. People with type 2 diabetes typically lose several percentage points less weight on these drugs than people without it, so this number beats retatrutide’s 18.8% in TRIUMPH-2, which enrolled a similar group. The cost is tolerability. Discontinuation ran between 10.8% and 27.0% across the combination arms versus 2.9% on tirzepatide alone, which is why the Phase 3 starting by year-end will use a slower dose escalation. For comparison, everything else at the European Association for the Study of Diabetes meeting landed well below that. Boehringer’s survodutide at 13%, AbbVie’s amylin candidate up to 10% at 12 weeks, Zealand and Roche’s petrelintide at 10.7% over 42 weeks. Lilly is mostly competing with its own pipeline at this point.

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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.

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VIDEO SUMMARY

THIS WEEK’S KEY TAKEAWAYS 🔑

Several Phase 3 wins were reported this week, but details were missing. Roche and Ionis reported that sefaxersen cut protein in the urine of IgA nephropathy patients, with no percentage. Amgen said dazodalibep produced a “statistically significant and clinically meaningful” improvement in Sjögren’s disease, with no score. Merck said its eye drug beat Lucentis in diabetic macular edema, with no letters of vision. Otsuka and Ionis said ulefnersen improved function and survival in a rare inherited form of ALS, with no hazard ratio. Merck rose 1% on an announcement containing no numbers.

The one company that actually disclosed data, including two anaphylaxis cases (1 more than placebo), was Celldex. I don’t think anaphylaxis will be a big problem for this drug long term. Dupixent carries an anaphylaxis warning and it is one of the biggest drugs in the world. But the stock fell 13% anyway. The market is currently punishing disclosures and giving a free pass to keeping numbers to yourself. However, this won’t last long because all numbers that are being withheld will have to be disclosed at medical meetings within months, and stocks will get repriced. I am just pointing out this new trend among larger companies that somewhat feels disingenuous.

The second theme is that manufacturing, not biology, is a constraint on the most advanced medicines right now. Telix paid $1.65 billion upfront for ITM, whose lead drug was rejected by the FDA in August for manufacturing and facility problems and nothing else. Ultragenyx’s Sanfilippo gene therapy was approved at $3.95 million, a year after its own manufacturing rejection. And Fyodor Urnov revealed that the base editing drug that saved Baby KJ cost $1.65 million to make, roughly double of earlier estimates. On top of all that, Anthropic said 950 Claude agents found a new CRISPR-like enzyme family in 21 hours, and gene editing stocks fell up to 11.6%. Nobody has actually shown what this system does yet, and Anthropic says so themselves. So while I agree that discovery is getting cheaper by the month and 21 hours is very impressive, the market reaction seems a little premature. Manufacturing is where the real bottleneck is now, and that’s what needs more attention.

Third, the gap between Lilly and Novo keeps widening. This week, Lilly got a second once weekly basal insulin approved and signed its fourth China discovery alliance since January 2025, worth up to $3.35 billion with InnoCare. Novo held its capital markets day and told investors to expect growth ‘broadly in line with industry peers.’ For a company that spent five years growing faster than almost anyone in pharma, that’s a significant downgrade. Shares fell about 5%.

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BIOTECH/PHARMA NEWS 🧬

🔹 The FDA approved Lilly’s Onswik (insulin efsitora alfa) on Sept. 24 for adults with type 2 diabetes, cutting basal injections from about 365 a year to 52. It’s the second weekly basal insulin in the US, six months after Novo’s Awiqli in March. The four trial QWINT program covered more than 3,400 adults. In QWINT-2, insulin-naive patients lowered A1C, the standard three month blood sugar measure, by 1.34% versus 1.26% on daily degludec, with clinically significant or severe hypoglycemia at 0.58 versus 0.45 events per patient year (rate ratio 1.30, 95% CI 0.94 to 1.78) and no severe episodes on efsitora. QWINT-3 showed a greater A1C drop than degludec at one year. It isn’t approved in type 1 diabetes, where severe hypoglycemia risk was higher. Price wasn’t disclosed. Separately, Lilly committed $100 million upfront and near term, plus up to $3.25B in milestones, to InnoCare (Beijing-based company) for compounds against up to five undisclosed targets. Lilly shares rose about 3%.

🔹 Telix agreed to buy ITM Isotope Technologies Munich for $1.65B upfront plus up to $700M in milestones. What Telix is buying is a rejected drug and a supply chain. ITM-11 (lutetium-177 edotreotide) won its Phase 3 COMPETE trial in gastroenteropancreatic neuroendocrine tumors, then received a complete response letter on August 7, citing only manufacturing and third party facility issues. Not safety, nor efficacy. A $100M milestone requires approval by Dec 31, 2027. The sharper point is the supply chain. ITM supplies the lutetium-177 used in Pluvicto, so Novartis’s isotope vendor is now owned by a competitor aiming directly at Lutathera, two weeks after the first generic Lutathera equivalent was approved. A day later Novartis licensed a preclinical radioligand from China’s BoomRay for up to $900M.

🔹 The FDA’s Molecular and Clinical Genetics Panel voted 7-2 with one abstention on Sept 23 that the benefits of GRAIL’s Galleri multi cancer blood test outweigh its risks for adults 50+. On safety the vote was 10-0, and on effectiveness it was a much closer 6-4. The 70k person randomized NHS-Galleri trial missed its primary endpoint, a reduction in stage 3 and 4 cancers (incidence rate ratio 1.03, p=0.63), while showing 14% fewer stage 4 diagnoses. In the 25,490 person PATHFINDER 2 study, the test flagged 0.54% of participants, with a positive predictive value of 60.3%, meaning about 4 in 10 positives led to a workup that found no cancer. Twelve month sensitivity was 39.3% across all cancers and 69.8% for twelve prespecified deadly ones, with specificity of 99.64%. The panel essentially endorsed a test that finds more cancers without proving it saves lives. Those aren’t the same thing, and the distinction is the central argument in cancer screening. GRAIL shares rose 12.3% to a 52 wk high. The premarket approval decision comes “in the coming months,” and coverage decisions will be argued over the stage 3-4 miss.

🔹 The FDA granted full approval on Sept. 17 to Ultragenyx’s Fayuvi (rebisufligene etisparvovec), the first treatment for Sanfilippo syndrome type A, a fatal childhood neurodegenerative disease with an average lifespan of about 15 years. The one time AAV9 gene therapy delivers a working SGSH gene. Approval rested on the Transpher A study against an external natural history control, and came after a July 2025 rejection over manufacturing. The list price is $3.95M,, justified against more than $8M in lifetime care costs. Jefferies models only about $250M in peak sales, and the second priority review voucher Ultragenyx received, worth about $200M at market rates, is nearly as valuable as the drug’s forecast annual revenue. The stock rose 13%. Six days later, Fyodor Urnov said the personalized base editor made for Baby KJ cost $1.65 million to manufacture, roughly double earlier estimates. For this to scale into N=1 platforms, that number has to fall by an order of magnitude.

🔹 Anthropic said 950 Claude agents, running for 21 h and processing about 210M tokens, narrowed more than 200k reverse transcriptases in public DNA databases to 3,500 unusual candidates and then to 20, identifying a family it calls array-associated reverse transcriptases. Wet lab work in its biosafety level 1-2 lab confirmed the associated repeat arrays produce short RNAs, which is what a guided DNA-cutting or editing system would need. The preprint, posted September 23, isn’t peer reviewed, and Anthropic says the system’s function is unproven and hasn’t been linked to programmable editing. Feng Zhang called it “genuinely intriguing.” The market treated it as a threat anyway, and CRISPR Therapeutics fell 5.5%, Beam 6.0% and Prime Medicine 11.6%. Gene-editing companies are valued on delivery, manufacturing and clinical data, not on owning a particular enzyme. What the result does show is that AI can now scan enormous genetic databases fast and cheap, which makes enzyme discovery less of a competitive advantage.

🔹 Celldex’s EMBARQ CSU1 and CSU2 trials randomized 1,939 patients with chronic spontaneous urticaria, meaning recurring hives and itch with no identifiable trigger, to barzolvolimab at 150 mg every four weeks, 300 mg every eight weeks, or placebo. The drug is an anti-KIT antibody that depletes mast cells, the immune cells that release histamine. It hit the primary endpoint on weekly urticaria activity score at week 12 in both trials, plus complete response at weeks 12 and 24. Complete response, meaning no hives and no itch, reached about 50% versus 15-18% on placebo at 24 weeks. In patients who had failed Xolair, the current standard, the 150 mg arms reached 55.3% and 41.7% complete response at week 12 versus 9.3% and 15.1%. That’s a clean signal in the population with the fewest options. The problem is two life threatening anaphylaxis cases on drug, with one more on placebo, plus neutropenia and hair and skin color changes. The stock fell 13% on the day. Cantor models $4.8B peak sales and filing is planned for 2027. Dupixent carries an anaphylaxis warning and sells billions, so this doesn’t automatically sink the drug, but it probably means a first dose monitoring requirement on the label.

🔹 Roche and Ionis’s Imagination trial hit its primary endpoint at a prespecified week 37 interim analysis in IgA nephropathy, a kidney disease where immune deposits damage the filtering units. Monthly self injected sefaxersen, an antisense drug that blocks production of complement factor B, reduced 24 hr urine protein-to-creatinine ratio versus placebo. Roche disclosed no magnitude. Safety matched earlier trials. The study stays blinded to week 105 for kidney function, and Roche will seek accelerated approval on proteinuria. The mechanism is the same as Novartis’s Fabhalta, which is a twice daily pill that can raise cholesterol, while sefaxersen showed no cholesterol effect in Phase 2. The field is crowded. Fabhalta, Otsuka’s Voyxact and Vera’s Trutakna are already approved, and Vertex’s povetacicept is pending. Ionis is due up to $400M in milestones. Roche says €1-2B peak, while analyst models sat near €400M by 2030 before the readout. Without the proteinuria percentage there’s no way to rank it against Fabhalta.

🔹 Viking Therapeutics’ 180 patient Phase 2 obesity study ran a 21 week weekly induction at 15 to 22.5 mg, producing 16-19% weight loss, then switched patients to less frequent shots for 12 weeks. Patients kept 82-97% of lost weight depending on strategy, about 90% on every other week dosing and 85% on monthly dosing. Only five patients discontinued for side effects across all arms, and GI effects didn’t differ meaningfully during maintenance. Leerink called it “stellar,” and the stock rose as much as 36%. There are two caveats though. Twelve weeks is a short maintenance window, and there was no comparison against simply staying on the weekly drug. Viking then did the rational thing and sold stock into the rally, pricing 7.86 million shares at $35+ $225M of 2% convertible notes due 2032, upsized to about $500M. Shares fell 13.4% on the pricing. Still early and still small, but it keeps alive the idea that monthly maintenance dosing is where independent obesity players can compete with Lilly and Novo.

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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: Matt Chinworth cen.acs.org

🎙️ 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 🔑

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.

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

🛒 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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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: 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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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.

Have a great long weekend and I will be back next week with This Week in Biotech #117.

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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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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.

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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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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.

📩 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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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?

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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 🔑

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.

Front cover image source: Associated press

🎙️ 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 me.

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

🛒 Check out our newly launched MERCH STORE.

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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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BIOTECH/PHARMA NEWS 🧬

🔹 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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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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A platform for personalized medicine

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

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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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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

More for everyone: how democratized tools can accelerate rare disease research.

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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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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

Skip the ex vivo middleman. Learn how advances in in vivo medicine can accelerate drug development.

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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 🔑

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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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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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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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.

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