AI Summary
→ WHAT IT COVERS Biotech Hangout Episode 185 covers ASCO 2026 highlights including PD-1/VEGF bispecifics, RAS inhibitor breakthroughs in pancreatic cancer, CDK4-selective inhibitors in breast cancer, GRAIL's multi-cancer detection trial failure, Abivax's ulcerative colitis safety signal, in vivo CAR-T early data, and the COINS Act debate over US-China biotech investment restrictions. → KEY INSIGHTS - **Biotech market positioning:** Year-to-date XBI is up 8% while semiconductors (SMH) are up 66%, but the 12-month view shows strong biotech recovery driven by M&A activity and a Q4 2025 rebound. Investors should evaluate biotech performance on a trailing 12-month basis rather than year-to-date to avoid misreading sector health amid AI-driven capital rotation. - **RAS inhibition breakthrough in PDAC:** Revolution Medicine's daraxonrasib sets a new standard of care in pancreatic ductal adenocarcinoma, improving median overall survival from 6.7 to 13.2 months versus chemotherapy. The drug targets KRAS G12D/V mutations, which represent roughly 80% of trial patients. Dose reductions manage tolerability issues including rash, stomatitis, and diarrhea without high discontinuation rates. - **CDK4-selective inhibitors outperform CDK4/6 class:** Pfizer's atirmociclib and BioNTech's BNT395 show 60–74% confirmed response rates versus roughly 50–55% for CDK4/6 inhibitors in HR+/HER2- breast cancer. BNT395 eliminates neutropenia by avoiding CDK6 modulation, enabling future combination strategies. Both drugs are now in Phase 3, with readouts expected in two to three years. - **COINS Act expansion risks US competitiveness:** Proposed BINZA legislation and a congressional letter from Representative Moolenaar would restrict US capital flows and licensing deals with Chinese biotechs. Panelists argue this benefits European pharma and funds, who face no equivalent restrictions, while slowing US patient access to medicines. The more defensible national security focus should target manufacturing supply chain dependency, not innovation licensing. - **GRAIL multi-cancer detection trial misses primary endpoint:** The MCED trial failed to show statistically significant reduction in Stage 3 and 4 cancers at three-year follow-up, with an IRR slightly above one. A 14% reduction in Stage 4 cancers was offset by an increase in Stage 3 detections. Test specificity and positive predictive value (~52%) remain strong, but the data raises unresolved questions about whether early detection translates to mortality improvement. - **In vivo CAR-T shows early promise with durability caveats:** Lilly's Colonya (formerly Cabaletta) demonstrated 100% ORR and MRD negativity in 18 relapsed/refractory multiple myeloma patients, but one patient relapsed and another turned MRD-positive by month three. Legend Biotech's lymphoma in vivo CAR-T showed 100% response rate and 83% complete responses at the higher dose level across six patients, with only Grade 1–2 toxicity at 2.2-month median follow-up. → NOTABLE MOMENT Abivax's ulcerative colitis maintenance data showed efficacy exceeding the 30% placebo-adjusted benchmark, yet the stock dropped 45% after seven malignancy cases emerged at the high dose versus one on placebo. Panelists noted the patient population carries elevated baseline cancer risk, similar to JAK inhibitors carrying black box warnings, but the dose-concentration pattern remains a regulatory overhang. 💼 SPONSORS None detected 🏷️ ASCO 2026, PD-1 VEGF Bispecifics, KRAS Inhibition, CDK4 Selective Inhibitors, COINS Act China Biotech, Multi-Cancer Early Detection