Healthcare fell 1.1%, with XBI (1.4%), NBI (1.1%) and BBC (2.2%) lower. Single names went both ways: Tango fell 16% after its ESMO update put the vopimetostat-Rasonque response rate at 82%, below the 92% it reported in August, while Lycia closed its Nasdaq debut at $30, 67% above its $18 IPO price.

Oil set the broader tone: Brent settled up 3.1% at $116.72, its highest since 29 April, after another wave of Houthi attacks on Saudi Arabia, and energy (+2.6%) led the S&P sectors. The Dow fell 1.2% (653 points) and the S&P 500 0.5%, while the Nasdaq 100 finished flat on a chip bounce. The October flash manufacturing PMI hit 56.0, a 53-month high, one-year inflation expectations rose to 4.7%, and the 10-year held just under 5% into this week's FOMC (Tuesday-Wednesday).

Roche's next-generation KRAS G12C inhibitor divarasib beat Amgen's Lumakras and Bristol Myers' Krazati head to head in the open-label Krascendo 1 trial (n=338, previously treated KRAS G12C NSCLC): median OS 17.7 vs 12.0 months, a 44% cut in the risk of death; median PFS 9.8 vs 5.7 months; ORR 58% vs 32%. Treatment-related discontinuations ran 4.8% vs 11.7%.

Why it matters: Most G12C trials have beaten docetaxel; this one beat the incumbents, and an OS split of nearly six months turns a second-generation label into a switching argument for payers and prescribers. The incumbents are small: Q2 sales were $111M for Lumakras and $55M for Krazati, so the hit to Amgen and Bristol Myers is lost relevance in first line more than lost revenue. Roche guides CHF1-2B peak, and that number depends on the recruiting Phase 3 of divarasib plus Keytruda against Keytruda-chemo in untreated nonsquamous disease. No filing date yet, and Roche dropped its docetaxel comparator study. Expect rivals to attack the open-label design; the survival gap is Roche's answer.

Source: Endpoints

More: Fierce Biotech

Amgen's DLL3-targeted T-cell engager Imdelltra plus AstraZeneca's Imfinzi cut the risk of death 58% versus Imfinzi alone as first-line maintenance in extensive-stage small cell lung cancer in the 563-patient Phase 3 DeLLphi-305 trial: median OS 21.1 months, 8.4 months longer, and median PFS 7.4 vs 1.9 months (a 66% cut). Grade 3+ treatment-related AEs ran 20.9% vs 10.8%, with grade 3 CRS in one patient (0.4%). The interim data were presented at ESMO and published in NEJM.

Why it matters: First-line maintenance turns Imdelltra from a second-line niche into the backbone of small cell care: Amgen puts the US population at 35,000-40,000 patients if the label extends, against about 13,000 today. No filing date yet. The bar now rises for every DLL3 follower: Boehringer used ESMO to pitch obrixtamig as a late-stage rival, and Roche paid Zymeworks $55M upfront on Friday for a preclinical trispecific billed as an Imdelltra challenger. The practical brake is monitoring. DeLLphi-305 tested 1-2 hours after infusion, while the US label still requires 6-8 hours for the first two doses (recently cut from 22-24), and that gap decides how fast community oncologists adopt it.

Source: Endpoints

More: Fierce Pharma

Bristol Myers disclosed that a patient with highly active relapsing multiple sclerosis died of septic pneumonia 44 days after a zola-cel (BMS-986353) infusion in the Phase 1 Breakfree-2 study, after late-onset neurological motor symptoms failed to resolve on steroids and IVIG. BMS reported no other deaths among 190 patients treated across its autoimmune zola-cel programs.

Why it matters: One death in 190 patients is a small number, but it lands on a modality whose autoimmune pitch is a one-time, drug-free remission, and the risk tolerance for that pitch sits closer to a biologic than to an oncology rescue. It follows the late-August pauses, when Novartis halted rap-cel studies after three IEC-HS deaths and Bristol Myers paused some trials over inflammatory events; the company now ties earlier lupus ICANS cases to a manufacturing reagent change. In Breakfree-2, CRS ran 42% (grade 2 in 6%), with one other life-threatening ICANS event. Kyverna, nearest to a first autoimmune CAR-T filing, carries the read-through, while in vivo CAR-T and T-cell engagers gain on tolerability by comparison.

Source: STAT

More: Endpoints; BioSpace

Bristol Myers and Biokin's bispecific ADC iza-bren cut progression risk 60% in post-TKI EGFR-mutant NSCLC (median PFS 11.1 vs 5.7 months) and 59% in pretreated HR+/HER2- breast cancer (8.2 vs 4.0 months) in two China Phase 3s, two of five positive so far. — Fierce Pharma

Akeso's ivonescimab won Phase 3 in first-line biliary tract cancer with positive overall survival versus durvalumab plus chemotherapy, presented in ESMO's Presidential Symposium. — Endpoints

AstraZeneca and Hutchmed's Tagrisso-Orpathys combo showed Phase 3 benefit after Tagrisso resistance in MET-driven, EGFR-mutant NSCLC. — Endpoints

Merck and Kelun's TROP2 ADC sacituzumab tirumotecan posted 15.0 vs 5.7 months PFS in PD-L1-negative NSCLC in OptiTROP-Lung06. — Fierce Pharma

Bayer's Nubeqa added to radiation and ADT lifted 4-year metastasis-free survival to 95% vs 88% (27 vs 63 events) in the 1,000-plus-patient Phase 3 DASL-HiCaP trial in very high-risk localized prostate cancer. — Fierce Pharma

J&J's RIPTAC candidate JNJ-6143 posted a 75% tumor response rate in advanced prostate cancer. — Fierce Biotech

Tango's vopimetostat plus Revolution's Rasonque showed an 82% response rate and 88% nine-month progression-free rate in advanced pancreatic cancer, below the 92% response rate Tango flagged in August; shares fell 16% Friday. — STAT

Takeda's Innovent-partnered claudin18.2 ADC posted a Phase 3 gastric cancer win with 10.2 months overall survival. — Fierce Biotech

Novartis said remibrutinib cut relapse rates by a third in pivotal multiple sclerosis trials. — STAT

Roche's sefaxersen reduced a kidney-damage marker 43.1% versus placebo in Phase 3 IgA nephropathy. — Fierce Biotech

Alnylam's brezosiran showed best-in-class huntingtin knockdown in Huntington's disease and heads to a pivotal study in 2027. — BioSpace

FDA lifted the clinical hold on Aardvark's ARD-101 in Prader-Willi after a healthy-volunteer ECG study found no cardiac events; Aardvark plans to resume PWS trials in 2027. — BioSpace

argenx reported strong Vyvgart sales, but a new confirmatory-trial requirement dented sentiment on execution. — Fierce Pharma

Roche licensed Zymeworks' ZW209, a preclinical trispecific T-cell engager pitched against Amgen's Imdelltra, for $55M upfront and up to $813M. — Fierce Biotech

Pathos raised $237M at a $3B valuation, led by Bristol Myers alongside a neuroscience collaboration with BMS and Tempus AI; JSKN-106 (TROP2/HER3 bispecific ADC, Phase 3) is a funding priority. — Endpoints

Warp Sciences, Kevin Weil's AI-and-robotics chemistry CRO, emerged from stealth with $215M led by Lightspeed, joined by Premji Invest, Mayfield, IVP and Lux. — Endpoints

Star Therapeutics raised $200M co-led by OrbiMed and Janus Henderson, joined by RA Capital, Redmile, Cormorant and Sofinnova Investments, after selling subsidiary Vega to Incyte for up to $2B in July. — Endpoints

Lycia priced an upsized IPO of 17.64M shares at $18, the top of its $16-18 range, for $317.5M gross (Nasdaq: LYCA; Jefferies, TD Cowen, Evercore, Guggenheim); its lead is the IgE-degrading cataLYTAC LCA-0061 in Phase 1 food allergy. — Endpoints

Bolt merged with private Prana Therapies in an all-stock reverse merger that pivots it to inflammation, paired with a $120M financing. — Fierce Biotech

Windward Bio (Basel) filed for a Nasdaq IPO under WWB to fund clinical-stage respiratory and eczema assets WIN378 and WIN027, licensed from Kelun-Biotech, Harbour BioMed and Qyuns, plus in-house R&D. — Endpoints

Relatlimab plus nivolumab showed 5-year survival and biomarker analyses in advanced melanoma from RELATIVITY-047. — Nature Medicine