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.

Jonathan Siddharth × Molly O'Shea

Healthcare AI has crossed O'Shea’s threshold for measurable impact, with biological and chemical models, laboratory robotics and simulations targeting drug development’s high failure rates.After a decade building licenses, networks and care infrastructure, Devoted Health tripled in size, halved operating expenses and significantly increased EBITDA, while China’s rising pharmaceutical research share leaves domestic research and regulatory capacity as risks to monitor.

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.

Thread Guy × Good Alexander

Hyperliquid’s sharp rerating came as feared CFTC enforcement looked less likely and tokenization gave chains a real economic race for assets, fees, and liquidity.Trump’s friendly policy signal, whatever its source, mattered more than ordinary four-year-cycle mechanics, while tokenized equities still carry jurisdictional and counterparty risks.A roughly 25% CLARITY Act passage scenario could ignite XRP, HBAR, and Canton, but major USDT outflows remain the clearest warning.

José × Michael Dempsey

Venture momentum is uniquely fragile: without scaled liquidity, dilution and preferred stacks can turn a softening bid into a 100% drawdown rather than 10–20%.Compound’s seed data finds that every valuation bucket above the bottom quartile produces similar top-decile outcomes, while Dempsey sees a 2028–2030 AI window and must rebuild the firm’s edge through higher-order analysis.

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.