Baker Bros. Advisors

**Signal Note: Baker Bros. Initiates Massive INCY Position** The reported position size (~$3 trillion) is almost certainly a data error — likely a misparse of share count or dollar value — and should be verified against the actual 13F filing before acting. That said, any genuine new Baker Bros. position in Incyte warrants attention given their concentrated, high-conviction biotech strategy and strong track record in hematology/oncology names. INCY's catalyst pipeline centers on ruxolitinib (Jakafi) lifecycle management ahead of eventual LOE (~2028), the ruxolitinib cream (Opzelura) ramp in atopic dermatitis, and pipeline readouts including axatilimab in chronic graft-versus-host disease (PDUFA) — a Baker-style bet would likely reflect conviction in underappreciated revenue durability or a near-term regulatory

## Signal Note: Baker Bros. Initiates Massive Position in BeiGene (BEIGF) Baker Bros. Advisors has taken a new position of ~8.8M shares in BeOne Medicines (formerly BeiGene), though the reported dollar value ($2.67T) appears to be a data error — at recent prices (~$200-230/share), the position is likely worth approximately $1.8-2.0B, which would still represent one of Baker's largest concentrated bets. This is a high-conviction signal given Baker's track record of deep scientific diligence in oncology: BeiGene's core asset zanubrutinib (BRUKINSA), a next-gen BTK inhibitor, is on a rapid global revenue trajectory (approaching $4B+ annualized run-rate) and has demonstrated superiority over ibrutinib in head-to-head trials across

**Signal Note: Baker Bros. Initiates Major Position in Madrigal Pharmaceuticals (MDGL)** Baker Bros.' new ~2.1M share position in MDGL represents a high-conviction bet on Rezdiffra (resmetirom), the first and only FDA-approved therapy for MASH (metabolic dysfunction-associated steatohepatitis) with moderate-to-advanced fibrosis — a market estimated at $30B+ peak potential with a massive underdiagnosed patient population. The position size (notably large even by Baker standards, though the reported dollar value appears to reflect a data anomaly) signals confidence in Rezdiffra's commercial ramp, with Street focus on quarterly script trajectory, planned label expansion into compensated cirrhosis (Phase 3 ongoing), and real-world outcomes data as key near-term catalysts. Baker's track record of concentrated, early-commercial-

**Signal Note: Baker Bros. Initiates ~$1.15B Position in Insmed (INSM)** Baker Bros.' new concentrated position in Insmed is a high-conviction bet almost certainly centered on brensocatib, a DPP1 inhibitor that delivered strong Phase 3 ASPEN results in bronchiectasis (reducing exacerbations ~21%) and is under FDA review with a PDUFA target date of August 2, 2025. The position size — over $1.1B — is extraordinary even for Baker Bros. and suggests confidence in both approval and commercial potential in a disease with no approved therapies in the US, representing a multi-billion-dollar market opportunity. Key near-term catalysts include the PDUFA decision and potential EU filing, with any Advisory Committee meeting (if scheduled) serving as an interim inflection point.

## Signal Note: Baker Bros. Initiates Massive ACAD Position **Flag: The reported position size (~$1.15 trillion) is almost certainly a data error — ACAD's entire market cap is ~$3-4B. This likely reflects an incorrect share count or pricing artifact in the 13F filing and requires verification before any action.** That said, if Baker Bros. has taken a meaningful new stake in ACAD, the signal is noteworthy. ACAD's primary value driver is **Nuplazid (pimavanserin)**, the only FDA-approved treatment for Parkinson's disease psychosis, generating ~$550M+ annually, alongside pipeline expansion into **negative symptoms of schizophrenia** and broader neuropsychiatric indications. Baker Bros.' concentrated, high-conviction style — typically initiating positions only when they see asymmetric clinical/commercial upside — suggests

**Baker Bros. Initiates Massive New Position in Celcuity (CELC) Ahead of Gedatolisib PDUFA** Baker Bros. built a significant new concentrated position of 38.7M shares in CELC, a high-conviction bet ahead of the July 17, 2026 PDUFA date for gedatolisib (pan-PI3K/mTOR inhibitor) in HR+/HER2- metastatic breast cancer, with a Phase 3 readout expected around June 2026 likely serving as the basis for the filing. The timing is notable given the catalyst density over the next 12-18 months—including Phase 2 data in mCRPC (Nov 2025) and the pivotal breast cancer readout—suggesting Baker Bros. has built conviction on the gedatolisib clinical profile ahead of de-risking events

**Signal Note: Baker Bros. Initiates Major Position in Revolution Medicines (RVMD)** Baker Bros.' new ~9.5M share position in RVMD represents an exceptionally high-conviction bet on the company's RAS(ON) inhibitor pipeline, particularly lead asset RMC-6236 (now briogatinib) targeting KRAS G12X-mutant pancreatic and non-small cell lung cancers, with pivotal readouts and a potential NDA filing on the horizon. **Note: The reported position value of ~$753B appears to be a data error — at recent share prices (~$37-42 range), the actual position value is likely ~$350-400M, which would still represent a significant concentrated allocation for the fund.** This is a strong directional signal given Baker Bros.' track record of sizing up ahead of major clinical catalysts in oncology, and investors should

**Signal Note: Baker Bros. Initiates Major Position in Kymera Therapeutics (KYMR)** Baker Bros. built a substantial new position in KYMR, a targeted protein degradation (TPD) company advancing KT-474 (an IRAK4 degrader) in pivotal trials for atopic dermatitis and hidradenitis suppurativa, with Phase 2/3 data readouts expected in 2025. Baker's concentrated, conviction-driven style makes a new position of this magnitude notable — the firm typically enters when it sees a high-probability clinical/regulatory catalyst approaching. The position size warrants scrutiny (the reported $673.6B notional appears to be a data error; based on ~8.66M shares at recent prices near $40-45, the true value is likely ~$350-390M), but even corrected, this represents a significant stake in

**Signal Note: Baker Bros. Initiates Major Position in Summit Therapeutics (SMMT)** Baker Bros. Advisors, the largest biotech-specialist fund known for extremely concentrated, high-conviction bets, initiated a new position of ~36.4M shares in Summit Therapeutics, representing a substantial capital deployment ahead of the Nov. 14, 2026 PDUFA date for ivonescimab, a bispecific PD-1/VEGF antibody in non-small cell lung cancer (NSCLC). The size and timing of this initiation suggest strong conviction in the ivonescimab regulatory pathway, likely informed by clinical data readouts positioning the drug as a potential best-in-class competitor to established PD-(L)1 and anti-angiogenic combination regimens. This is a high-signal move given Baker Bros.' track record of deep diligence in onc

**Signal Note: Baker Bros. Initiates Major Position in Rhythm Pharmaceuticals (RYTM)** Baker Bros. building a substantial new position in RYTM is a high-conviction signal given their track record of concentrating in names where they see significant commercial inflection or pipeline catalysts — Rhythm's lead asset setmelanotide (IMCIVREE), an MC4R agonist approved for rare genetic obesity (BBS, POMC, LEPR deficiencies), is in active label expansion with potential broadening into additional MC4R pathway obesities and hypothalamic obesity, representing a meaningful TAM expansion story. The ~5.6M share stake (note: the reported dollar value appears to contain a data error and likely represents ~$280-320M based on recent share prices around $50-57) would represent a significant ownership percentage, consistent with Baker Bros.' pattern of taking outsized positions ahead of key

## Signal Note: Baker Bros. Initiates Massive Position in Kodiak Sciences (KOD) **Note: The reported position value of ~$557B is almost certainly a data error in the 13F filing — likely reflecting a misplaced decimal or unit issue. Based on 19.9M shares and KOD's recent trading range (~$3-5), the realistic position value is approximately $60-100M. Analysts should verify against the original filing.** That said, Baker Bros. initiating a new ~20M share stake in KOD is a significant signal. Kodiak's lead asset is tarcocimab (KSI-501), an anti-VEGF/IL-6 bispecific antibody-trap for wet AMD and diabetic macular edema. The program suffered a major setback when Phase 2b/3 BEACON data showed non-inferiority failure

**Signal Note: Baker Bros. initiates major position in Praxis Precision Medicine (PRAX)** The reported position size of ~$332B is almost certainly a data error (likely reflecting an incorrect price or share count), but the core signal — Baker Bros. opening a new concentrated position in PRAX — is noteworthy given their track record of high-conviction bets ahead of clinical catalysts. Praxis's lead asset is ulixacaltamide (T-CALM), a T-type calcium channel modulator in Phase 3 for essential tremor (PRAX-562 study), with topline data expected in 2025, alongside earlier-stage programs in mood disorders (PRAX-403). Baker's entry pattern is consistent with positioning ahead of a pivotal readout in a CNS name with limited competitive overlap, though the filing data should be verified for accuracy before sizing conclusions are drawn.

**Signal Note: Baker Bros. Initiates Major Position in Alkermes (ALKS)** **Note: The reported position value of ~$280B appears to be a data error — based on 10M shares and ALKS's recent price (~$28-$32/share), the actual position is likely ~$280-320M, which would still represent a significant concentrated bet.** Baker Bros. building a new position of this magnitude in ALKS is notable given their track record of high-conviction biotech bets; the likely thesis centers on the continued commercial ramp of Lybalvi (olanzapine/samidorphan) for schizophrenia and bipolar I disorder, which has been on a strong growth trajectory with quarterly revenues accelerating, plus the durable cash flows from Vivitrol (opioid dependence) and their royalty stream from Biogen on Vumerity (

## Signal Note: Baker Bros. Initiates Massive Position in GRAIL (GRAL) The reported position value of ~$178.5 billion is almost certainly a data error (likely reflecting a filing quirk or price miscalculation), but the underlying signal — Baker Bros. initiating a new 2.09M share stake in GRAIL — is noteworthy. GRAIL's core asset is Galleri, a multi-cancer early detection (MCED) blood test capable of screening for 50+ cancer types, with the company pursuing an FDA PMA submission and awaiting a potential Medicare coverage decision, both of which represent major binary catalysts. Baker Bros. running an extremely concentrated book and opening a new position in GRAIL suggests high conviction around the regulatory/reimbursement pathway for Galleri, likely timed ahead of expected FDA and CMS milestones — investors should verify the dollar value but

## Signal Note: Baker Bros. Initiates Major Position in Edgewise Therapeutics (EWTX) Baker Brothers, the largest biotech-dedicated fund known for extremely concentrated, high-conviction bets, initiated a new position in EWTX — a significant signal given their track record of early positioning ahead of pivotal catalysts. Edgewise's lead asset, sevasemten (EDG-5506), is a novel cardiac myosin inhibitor in Phase 2/3 development for obstructive hypertrophic cardiomyopathy (oHCM), differentiating from Bristol-Myers' mavacamten on selectivity and potentially a cleaner safety/monitoring profile; Phase 3 MAPLE-HCM topline data is anticipated in 2026. **Note:** The reported dollar value (~$163B) appears to be a filing anomaly — based on ~6