Paul Matteis

Sam Fazeli × Josh Schimmer × Eric Schmidt × Paul Matteis × Matt Herper

AstraZeneca’s eplontersen failed its ATTR cardiomyopathy outcomes trial, with Ionis reporting no benefit in the tafamidis-combination group, including no CV-biomarker effect.The readout improves Alnylam’s perception, but royalty-free Nucresiran must still show whether its adjunctive outcomes study preserves silencer-plus-tafamidis synergy; Agios’ mitapivat won priority review despite missing its co-primary VOC endpoint.Atumelnant’s liver-enzyme elevations remain a risk to monitor.

Graig Suvannavejh × Eric Schmidt × Paul Matteis × Oliver Barnes

Biotech is outperforming healthcare, with XBI up 10.5% year-to-date and Parabilis Medicines setting a $771M IPO record.Selective capital remains pivotal: Summit withdrew its $500M offering before the binary global HARMONi-3 readout, while Tango and Revolution reported a 90%+ response rate.Major deals and regulatory shifts offer catalysts, but financing needs, commercial competition, and follow-on capital allocation remain unresolved risks.

Chris Garabedian × Paul Matteis × Tess Cameron × Adam Feuerstein

XBI strength, Kylera’s IPO above $625M before the shoe, and fresh S-1 and PIPE activity suggest financing is reopening, though the index now favors larger, liquid companies.Revolution Medicines’ 0.4 overall-survival hazard ratio in second-line pancreatic cancer and $2B raise could fund commercialization, while Travere’s proteinuria-based FSGS approval despite eGFR underperformance leaves Vertex’s high-risk enaxopin Phase 3 regulatory bar unresolved.

Graig Suvannavejh × Paul Matteis × Brian Skorney × Yaron Werber × Chris Garabedian × Adam Feuerstein

George Tidmarsh’s CBER departure and UniQure’s rejected filing after FDA alignment expose a widening gap between flexible guidance and unpredictable execution.UniQure reported 80% disease slowing at two years and 75% at three years for high dose, while Sarepta’s failed ESSENCE study and December’s Stoke meeting will test evidence standards and early-filing appetite.

Chris Garabedian × Brad Loncar × Eric Schmidt × Paul Matteis × Tess Cameron

Biotech markets face policy and macro instability as rising bond yields and a weaker dollar overshadow a temporary tariff-pause rally.With private capital confronting scarce company formation and weaker public comparables, catalysts must prove their case, while royalty financing offers earlier funding but can leave debt-like repayment obligations when programs fail.