Episode 201 - October 30, 2026

Sam Fazeli opened with takeaways from recent pharmaceutical earnings reports. Eli Lilly said it would continue emphasizing early- and clinical-stage deals and expected activity across therapeutic areas, with particular interest in immunology, neuroscience, and oncology. Bristol Myers Squibb said it remained agnostic about deal size and would allocate capital opportunistically rather than wait for a specific transaction; the company reportedly had $13 billion in cash and marketable securities, in addition to debt access. Novartis reiterated its preference for transactions below $2 billion, while reserving room for larger deals selectively. The company’s view did not appear to change after disappointing news involving an asset whose trial outcome investors had been watching. The hosts interpreted these comments as evidence that large pharmaceutical companies remain active across the therapeutic continuum. Sam also said investor and venture-capital activity could produce a stronger fourth-quarter M&A market than the third quarter, particularly with Jefferies and the J.P. Morgan conference ahead. On China, Sanofi’s CEO described the country as a “thriving hub for scientific advancement” and said Sanofi would source innovation globally, including from China. Sanofi’s R&D head, Paolo, highlighted faster translational efficiency as a potential advantage of working with Chinese partners, while the company’s commercial presence could support manufacturing and partnerships.

Greg Suvannavejh discussed Alnylam Pharmaceuticals’ third-quarter results and the sharp reaction in its stock. The company’s ATTR drug Amvuttra generated $81 million in quarterly sales, although Greg later corrected himself: the $81 million figure represented U.S. demand, while total revenue was $1.13 billion. The U.S. demand figure declined from $129 million in the second quarter, a meaningful drop in an increasingly competitive market. Alnylam’s CEO called the result unsatisfactory despite a recent increase in the sales force, and the company lowered its full-year product guidance for the second time. The stock fell about 30% during the week and was down approximately 60% year to date. Greg said the episode illustrated that strong clinical data and industry accolades do not guarantee a successful commercial launch: “when you try to launch your own drug, the rubber kind of hits the road.” Chris noted that some investors had expected Alnylam to use its strong stock currency and strategic position to make an acquisition that would diversify its pipeline. The group suggested that the company may now need to consider that question more seriously, beyond its current franchise.

Brian Skorney introduced Anthropic’s S-1 filing, which contained unusually prominent discussion of life science as a strategic expansion area. The filing cited Anthropic’s April acquisition of Coefficient Bio, a computational-biology company, and the group also discussed the acquisition of Mithril Medicine, described as a one-person biotech founded by Cody Tranbargar. Brian said Tranbargar was known to several hosts through an annual running group and had also revealed himself as the person behind the X/Twitter persona Professor Oak. The acquisition led to a broader argument about whether AI companies will merely improve biotech efficiency or eventually absorb drug development themselves. The hosts rejected claims that AI will cure all diseases within 10 years as overhyped, but agreed that AI can increase the number of “pucks” available for drug discovery, especially around validated targets, chemistry, data analysis, patient identification, and trial-site selection. They emphasized that new-target biology remains much harder because human disease mechanisms and translational models are still poorly understood. Yaron Werber said AI’s strength is particularly clear when large datasets must be gathered and sifted: his team can replace two or three contractors for some data-collection tasks, although humans are still needed to check quality. The group also noted that AI is encouraging smaller, more virtual biotech teams with fractional executives and outsourced functions. Brian cautioned that AI systems still make mistakes when the underlying data are poor, and that AI cannot eliminate the fundamental need to run long, expensive human trials.

The hosts continued the AI discussion by separating operational improvements from true biological breakthroughs. Chris argued that biology may be the hardest scientific problem to transform; if biotech becomes fully automated, few other industries would remain untouched. The group agreed that AI could help identify protein-protein interactions, model protein movement, and find previously “undruggable” targets, but those predictions still require extensive laboratory and clinical validation. Yaron pointed to Amgen as an early example of a practical benefit. Amgen has used informatics and AI for patient identification, site identification, and site mapping, and enrolled an IgA nephropathy study in 16 months—roughly a year and a half faster than Novartis took to enroll a comparable study, according to the discussion. Better enrollment could raise the probability of technical or regulatory success even if it does not change the biological duration of a trial. Brian stressed that the main bottleneck is not necessarily target identification or molecule design. A cardiovascular outcomes study may still require 10,000 patients, take five years, and cost $300 million; AI does not yet provide a way around that. Greg similarly said AI might improve patient selection and increase the probability of success, but a six-week, six-month, or two-year outcome study will still take that long. The panel therefore expects meaningful but initially incremental gains rather than a 90% acceleration of drug development.

Greg described a mixed but active biotech IPO market. By his unofficial count, roughly 31 biotech companies had gone public year to date, approaching the total of 50 offerings that Josh Schumer had predicted might be possible. Lycia Therapeutics, a protein degrader company, rose about 60% on its first trading day before settling at roughly a 30% gain. Two other companies were debuting during the episode: Bionova Therapeutics, developing bispecific antibodies for immune-mediated diseases including atopic dermatitis, and Aspen Neuroscience, a cell-therapy company targeting Parkinson’s disease. The fact that Bionova and Aspen were Phase 1 companies suggested that investors still had some appetite for early-stage risk. At the same time, Greg said at least half of the year’s IPOs appeared to be trading below their debut prices. He cited Ikena Therapeutics, which had gone public at $18 in February and was trading near $5 despite holding more than $500 million in cash. Chris saw reasons for optimism, including possible M&A, more than 50 novel-drug approvals already during the year, and roughly 10 additional FDA decisions expected before year-end. Sam offered a more cautious macro view. He warned that a major geopolitical attack and retaliation could drive oil prices and interest rates higher, while tariffs could return after the midterms and add inflationary pressure. Higher risk-free returns could make investors less willing to fund biotech, even if sector-specific fundamentals improve.

Chris discussed an FDA rare-disease pathway meeting intended to create a more standardized, fit-for-purpose review process across the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research. The proposed framework would account for small sample sizes and enrollment limitations, coordinate reviews through the FDA Rare Disease Innovation Hub, clarify expectations for real-world evidence, institutionalize patient and disease-expert input, and allow more flexible chemistry, manufacturing, and controls approaches when products are made in small batches. Chris said the effort formalizes flexibility the FDA has discussed for more than a decade. He then described Plowshare Therapies, which raised $7 million from angel and philanthropic investors to pursue a gene-therapy approach for maple syrup urine disease in the Amish and Mennonite communities of Pennsylvania. Kevin Strauss, who had led a clinic for children with special conditions, became CEO and had already worked with the community, including helping patients obtain access to Zolgensma for SMA. The company views insular communities as potential platforms because multiple rare genetic mutations can cluster within them. Plowshare had received an orphan rare-pediatric designation and could potentially benefit from priority-review vouchers, but Chris warned that $7 million is only enough to begin the work. Institutional investors will eventually need to provide the capital required for clinical development and commercialization. The hosts viewed the philanthropic and community support as encouraging in a field where many programs struggle to attract conventional financing.

Brian reviewed Kidney Week, where IgA nephropathy emerged as a particularly active development area. The disease affects roughly 200,000 diagnosed people in the United States and involves immunoglobulin A-related inflammation that gradually scars the kidneys and can lead to kidney failure. Recent approvals include Filspari and Tarpeyo, while newer drugs such as Novartis’ Fabhalta and Ultomiris target complement-mediated inflammation. The strongest results, in Brian’s view, came from Otsuka’s Voyxact in the Phase 3 Visionary study. The full two-year dataset, published in the New England Journal of Medicine alongside other kidney-disease papers, showed essentially no decline in estimated glomerular filtration rate compared with a steady decline on placebo. The composite kidney outcome had a hazard ratio of 0.029: one kidney event occurred in the treatment group versus 28 on placebo. Kidney-replacement therapy occurred in zero treated patients versus five placebo patients. The once-monthly subcutaneous injection also appeared safe. Other programs produced encouraging results. Vera Therapeutics’ atacicept showed reductions in kidney outcomes and slowed eGFR decline. Vertex’s povetacicept, which had an FDA action date about a month away, showed similar proteinuria results in an interim Phase 3 analysis. Brian noted an ongoing debate over whether targeting APRIL alone or APRIL plus BAFF is necessary, but concluded that B-cell and APRIL-directed approaches are materially improving outcomes. Chris also mentioned Climb Bio’s early data with its APRIL-targeting drug, supported by a consistent dataset from Chinese partner Mabworks.

Sam and Yaron described ESMO in Madrid as data-rich and exhausting, with major presentations including Amgen’s Delphi 305 study in small-cell lung cancer, Roche’s KRAS G12C inhibitor data in non-small-cell lung cancer, AstraZeneca’s gastric-cancer results, and Moderna’s cancer-vaccine data. They debated whether Moderna received a true standing ovation, concluding that any applause was not especially surprising because the data had already been released before the presentation. Moderna’s pancreatic-cancer poster involved only about 19 or 20 patients, but roughly half generated 34 new antigens, a potentially encouraging result given pancreatic cancer’s low tumor-mutation burden. Yaron contrasted Moderna’s unmodified-mRNA approach with BioNTech’s platform, which targets 20 neoantigens and uses a different delivery system. Amgen’s Delphi 305 produced what Sam called practice-changing overall-survival data in small-cell lung cancer. The hosts expect the forthcoming Delphi 312 study to be important as well and said positive results could establish a new treatment setting for follow-on DLL3, B7-H3, and other ADCs. They also discussed Summit’s ivonescimab data in first-line biliary-tract cancer, which improved overall and progression-free survival over chemotherapy, and Genmab’s series of successes. Genmab’s first-line cancer program reduced progression or death by 51%, while its ovarian-cancer study showed a roughly 60–70% reduction in deaths against a standard-of-care comparator. Updated head-and-neck data also showed about a 50% survival reduction regardless of HPV status. The hosts said these programs could largely offset Genmab’s expected 2029–2030 Darzalex royalty cliff. They closed by noting strong early data for Tango’s PRMT5 program but concerns about a threefold increase in the exposure of the partnered RAS drug, alongside competition from BMS’s BMS-986466 program.