Chris Garabedian × Graig Suvannavejh × Sam Fazeli × Brian Skorney × Yaron Werber

Pharma buyers remain active in early-stage assets and China, though term sheets do not guarantee Q4 closings.Amvuttra sales fell to $81 million from $129 million in Q2 as Alnylam cut franchise guidance for a second time this year.AI may reduce data-gathering costs, but a 10,000-patient cardiovascular study still takes five years and $300 million.

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.

Michael Dempsey

AI vendors growing 6x in a market expanding 10x may be losing ground, while stack convergence could put $30 billion businesses at risk of displacement within nine months.Compound’s roughly 23-company portfolio includes 16 biotech businesses and only three AI investments, reflecting Dempsey’s preference for scientific ventures that control a route from discovery to commercialization.

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.

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.