Episode 137 - April 4, 2025

Summary

• Pharma tariffs were a coming cost and supply-chain problem, but the panel ranked FDA instability as the more consequential threat to biotech. Pharmaceuticals escaped the initial U.S. tariff package, although President Trump said the administration was “working on it”; meanwhile, XBI was down roughly 8% week to date. Brad Loncar called tariffs disruptive but “not even top five” among an industry’s problems when “pretty much everybody but us” wants biotech smaller, less profitable and less used.
• The FDA sits at a genuine policy fork after Peter Marks’s resignation, mass layoffs and the loss of senior scientific leadership. Brad’s core concern was not headcount alone but that “we don’t know whether FDA is going to get more stringent or less stringent”; either direction would reshape valuations. Nina Kjellson and Yaron Werber worried that institutional knowledge painstakingly built across novel modalities, biomarkers and complex diseases could be lost, reviving memories of the dysfunctional 2005–07 period.
• Upcoming rare-disease decisions will test whether prior FDA agreements and accelerated-approval flexibility still hold. Ultragenyx’s Sanfilippo gene therapy, REGENXBIO’s Hunter syndrome program and Denali’s Hunter therapy all rely on CSF heparan sulfate as a biomarker in diseases historically requiring clinical data. Denali’s filing was encouraging because it spoke with its FDA review team the day before filing, but Paul Matteis’s question remains: “Is what you heard from the FDA in the past year still ringing true?”
• The measles outbreak made failures of public-health leadership tangible rather than ideological. Nina cited roughly 500 confirmed cases across 20 states, 93% associated with outbreaks, infectious spread to perhaps 12–20 people per case and a 95% vaccination threshold for herd immunity. She characterized Secretary Kennedy’s treatment recommendations and claims that the vaccine was risky, resembled measles itself and had a fatality rate as concerning misinformation that could deepen hesitancy around a vaccine estimated to have prevented 93.7 million deaths from 1974 through 2024.
• Biopharma faces a credibility trap: silence looks cowardly, but advocacy can be dismissed as self-interest. Former FDA commissioner Robert Califf had reportedly called the industry “cowards,” while Brad argued pharma has “less than zero” moral authority and Paul doubted Wall Street would be an empathetic messenger. Eric said he and Josh had publicly argued that Peter Marks was unfairly fired and questioned whether Secretary Kennedy should remain in position. Nina’s actionable middle ground was to defend trust in science, explain global supply chains, invest visibly in U.S. manufacturing skills and support academic research if capital retreats from early science.
• The week’s company data punished ambiguity, especially when a drug’s thesis depended on superior safety. Vaxcyte fell roughly by half from about $70 after several serotypes missed in what Brad said research he read characterized as a pediatric Phase 2 conjugate-vaccine study, though formulation changes could preserve a pivotal path. Edgewise showed activity across HCM biomarkers, but a couple of atrial-fibrillation cases left investors unable to exclude a drug-related safety signal from a small dataset—an especially fragile setup in a “sell the news” market.
• Lp(a) supplied the episode’s strongest constructive clinical and commercial thesis. Lilly’s lepodisiran produced a 93.5% reduction at 400 mg around six months in Phase 2, while Ionis/Novartis’s 8,300-plus-patient pelacarsen HORIZON study is powered at 90% to show a 20% benefit, with its readout delayed from the second half of this year into the first half of next year. Yaron remained bullish despite less-frequent competitors: outcomes data, first-mover advantage and a patient-friendly autoinjector could matter more than dosing frequency alone.
• Capital formation and timely approvals offered limited evidence that the drug-development machinery was still functioning. Isomorphic Labs raised $600 million to apply AlphaFold 3 to protein and protein-ligand discovery, while Denali and Ultragenyx reported active FDA engagement. Amgen’s Blincyto received a new indication, Cabometyx received its neuroendocrine-tumor expansion slightly early, and Novartis’s Vanrafia won a favorable label without a boxed warning or REMS—suggesting late-stage reviews were, for now, still moving.

Deep dive

Not yet available upstream; scheduled sync will retry.