Episode 188 - July 10, 2026

Summary

• The week’s biggest tradeable shock: AstraZeneca’s eplontersen failed its ATTR cardiomyopathy outcomes trial, and Sam Fazeli reported from Ionis that in the tafamidis-combination group “no benefit means no benefit” — nothing on secondary endpoints or even CV biomarkers. Alnylam opened up ~17% on the perception that it now owns the silencer market, but Sam flags the catch: Amvuttra pays Sanofi a 20–30% royalty, so royalty-free Nucresiran must succeed — and its largely adjunctive outcomes study now faces a direct question about whether this readout undermines silencer-plus-tafamidis synergy. Josh Schimmer says some observers think another positive TTR cardiomyopathy readout may never come.
• The FDA is quietly re-sealing complete response letters: none have been released since April, coinciding with a Covington & Burling citizen petition arguing publication breaches sponsors’ confidential information. Matt Herper calls CRL transparency “one of the best things” Makary did while noting Makary’s habit of “not really worrying about legality” first; meanwhile Rick Pazdur is “definitely in the mix” to return, though Herper cautions he’d want “some substantial control” and the administration “hasn’t loved people who are critical.”
• Agios’ mitapivat won priority review in sickle cell despite missing its co-primary VOC endpoint — no AdCom required — and Eric Schmidt reads it as proof “the FDA is open for business” on rare disease. He’d reprice Replimune and Aiolos from 10–20% approval odds to “maybe close to 70 or 80%,” with Regenxbio and peers right-shifted too; Paul is less sweeping — uniQure at ~$40 still prices only about halfway to approval, and “maybe every situation is different.”
• Vertex bought Crinetics for ~$10B ($9B net of cash), a near-100% premium, marking rare endocrinology as the next niche to “get hot.” Paul’s take: the only real risk is atumelnant’s liver signal (seven enzyme elevations, all mild, self-resolving), floor value looks like $1B+ per drug versus Vertex’s claimed $5B combined, and at a $130B cap “this is the kind of stuff they should be doing.” Josh mourns losing an endocrine company with “essentially no target risk.”
• European acquirers are suddenly aggressive: Ipsen paid $450M upfront for Kartos Therapeutics (phase 3 myelofibrosis) and €200M for Memo Therapeutics, while Novartis paid $1.1B cash upfront for preclinical UK ADC company Myricx — “a little bit rich,” so “there must be something really exciting in there.” BridgeBio separately banked a $1B Sixth Street/KKR royalty financing ahead of three launches in 12 months, with the Attruby launch already “exceptional.”
• Herper’s dispatch from Anthropic’s Claude for Science launch: “AI is really cool and nobody knows what to do with it” — but even the mundane case is big. BMS’s Chris Boerner cites “5 to 10% efficiencies but across the board,” and the modest scenario — development time down 30%, success rates from 8% to 16% — is “astounding”: “you don’t have to do what Dario says we’re going to do for things to change a lot.” The unsolved problem: biology lacks coding’s fast feedback loop.
• AAIC’s main event Tuesday: full data on Biogen’s anti-tau ASO, which missed its dose-response primary because the lowest dose did best — yet Biogen is going to phase 3 with two large randomized studies. Paul stays constructive because tau has “the strongest scientific rationale for a disease-modifying target in Alzheimer’s”; the real question is whether the data hands the play to IV brain-shuttle rivals such as Denali and Arrowhead. Eric’s buy-side checks run “9 to one” negative, and both confess “PTSD from Alzheimer’s.”
• Tape check: despite the day’s pullback, the XBI is up 30% YTD and nearly 80% year-over-year — M&A froth is “a dangerous place,” but “industry fundamentals [are] better than they’ve ever been.” Revolution Medicines added another win: G12D-selective zoldonrasib posted 82% ORR/96% DCR with FOLFIRINOX in first-line pancreatic cancer, though Eric says the G12D-plus-pan-RAS combination did not look much better than pan-RAS alone and is unsure there is synergy.

Deep dive

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