Biotech Hangout

Daphne Zohar × Brad Loncar × Chris Garabedian × Sam Fazeli × Eric Schmidt × Josh Schimmer × Matt Gline × Ali Mortazavi

Moderna’s selloff puts a near-$100 billion valuation against $2.2–2.3 billion in annual revenue and established melanoma competition, though Loncar says the data strengthened the medical and commercial case.Tango’s PRMT5 inhibitor delivered an 82% response rate and 88% non-progression at nine months in heavily pretreated pancreatic cancer, but its shares fell; the MTAP-deleted opportunity may cover 30–40% of patients.

Graig Suvannavejh × Paul Matteis × Brian Skorney × Yaron Werber × Jake Becraft

XBI remains up 20% YTD but fell from 169 to roughly 146 amid biotech’s largest cumulative hedge-fund de-grossing in more than five years.IPO markets remain open but favor clinical catalysts and defensible IP; M&A could restart buying, while Bristol’s low-dose-only significant admilparant result supports LPA1 in IPF but leaves dose response unresolved.

Graig Suvannavejh × Sam Fazeli × Eric Schmidt × Brian Skorney

Biotech’s 27% XBI gain through September masks a punishing ownership unwind, as underowned and heavily shorted names offset specialist-fund selling.Regeneron-Sanofi’s $1 billion upfront and AstraZeneca’s $2 billion Summit investment show strategic capital is flowing, but HARMONi-3 remains a potentially historic binary event.China-origin deals and Lilly’s obesity data sharpen competition, while financing, durability, tolerability, and endpoint risk still dictate outcomes.

Sam Fazeli × Yaron Werber × Brian Skorney × Matt Gline

Biotech’s healthy headline tape masked long-short degrossing and rate sensitivity, while 22 IPOs and record-period average proceeds showed primary-market resilience.MFN may rebalance global contributions through revenue sharing rather than simply cut U.S. prices, but Europe could restrict access or favor cheaper Chinese drugs; meanwhile, durable VK2735 efficacy, Celldex safety and Vertex’s interim analysis define catalysts.

Josh Schimmer × Eric Schmidt × Paul Matteis × Adam Feuerstein

XBI fell roughly 4% month to date and 9%-10% from its highs, but remained up about 30% for the year, suggesting nervous consolidation rather than a broken thesis.Xenon’s nearly 30% selloff after pausing depression enrollment came despite no clinical hold and about 360 patients enrolled, showing how bounded safety data can become a franchise scare.Sionna’s failed add-on study reinforced Vertex’s cystic-fibrosis moat, while a switch study remains the key test.

Tess Cameron × Brian Skorney × Paul Matteis × Yaron Werber

HORIZON was “completely negative” despite pelacarsen reducing Lp(a) 80%, challenging biomarker shortcuts as Amgen fell 10% on read-through.Novartis’s Avidity failure less than a year after the $12 billion acquisition drove Artisan’s sales cut of about $5 billion and EPS CAGR to 4%.Dyne’s 25% placebo-adjusted CASI-22 splice correction and Roivant’s 56% PVR reduction set up catalysts, while endpoint and outcome risks remain.

Daphne Zohar × Eric Schmidt × Sam Fazeli × Graig Suvannavejh

Biotech’s 80% XBI rally is structurally M&A-led, with roughly $138B announced against $59B of equity issuance, compressing premiums and leaving no preclinical IPOs.Moderna’s melanoma vaccine suggests a durable trade-secret franchise, while BioNTech’s colorectal failure leaves tumor context unresolved; daraxonrasib’s $478K price and frontline label, and ivonescimab’s HARMONi-3 in 6–9 months, set the key monitoring points.

Chris Garabedian × Graig Suvannavejh × Paul Matteis × Tess Cameron

Biotech’s tape is “healthy but discerning,” with 19 Nasdaq issues year-to-date and the XBI outperforming, yet market-neutral shorts have struggled as heavily shorted names such as Crinetics and Apogee were acquired.Tenex and Sionna failures show how sharply negative data is punished, while MindMed’s durable Phase 3 LSD effect and Belite’s February 12, 2027 PDUFA create catalysts amid continuing diligence and competitive risks.

Sam Fazeli × Brian Skorney × Yaron Werber × Jake Becraft

Biotech’s washout is intensifying: 16 of 18 2024 IPOs trade below issue at a median 61% decline, despite Jake Becraft seeing fundamentals intact.Weak commercialization economics reinforce M&A dependence; Pfizer’s planned BD activity and obesity interest, plus Jazz-Chimerix and AbbVie-Gubra, point to catalysts while Pliant and Biohaven test differentiation.

Graig Suvannavejh × Tim Opler × Yaron Werber × Paul Matteis × Brian Skorney

Biotech is decisively outperforming, with XBI +24% YTD versus +9% for the S&P 500, as Graig sees FDA headwinds turning into tailwinds alongside 14 IPOs and $300B+ of pharma revenue at LOE risk.Reverse mergers now rival traditional IPOs, while J&J’s $785M Sail deal and $2.6B acquisition option reinforce hot in vivo CAR-T M&A.Alnylam’s roughly 30% TTR sell-off and Novo’s ZEUS miss leave upcoming data and year-end M&A as key tests.