Session IX — Drug Discovery IV
The Elimination Imperative: From Pathogenic Cells to Durable Remission
Three leaders — Robert Plenge (BMS), Flavius Martin (Gilead), and Kendra Rose (Bayer) — converge on a thesis: the future belongs to molecules that eliminate disease’s cellular root causes, not just manage symptoms.
Robert Plenge (BMS) — Five Principles, Three Drugs
Key Drugs
- Deucravacitinib (Sotyktu) — TYK2 allosteric inhibitor; genetics (P1104A variant) → pseudokinase domain → clinical validation
- BMS-986470 — CELMoD dual degrader (ZBTB7A + WIZ) for sickle cell; AI broke a months-long MPO impasse
- CD19 CAR-T for lupus — registrational trial based on Georg Schett’s NEJM case series; immune reset
The Dream Lab
- Deep mutational scanning at scale (with Octant) to guide AI target nomination
- Automated design-make-test-analyze closed loops
- Real-time mechanistic models in clinic
Flavius Martin (Gilead) — One Biology, Many Modalities
Unified Elimination Thesis
In virology: eliminate every infected cell. In oncology: every malignant cell. In autoimmunity: every pathogenic B/plasma/autoreactive T cell.
Three Modality Examples
- FC-enhanced anti-CCR8 — Treg depletion in immuno-oncology
- Tubulis ADC (TUB-040) — next-gen linker (P5 platform); 50% ORR in platinum-resistant ovarian ($3.1B acquisition)
- Anito-cel — BCMA CAR-T (Arcellx D-Domain binder); 96% ORR, 74% CR in myeloma; BLA accepted, PDUFA Dec 2026 ($7.8B Arcellx acquisition)
- Gamgertamig — BCMAx CD3 T-cell engager for autoimmune diseases; single-cycle SubQ → deep B/plasma-cell depletion
Kendra Rose (Bayer) — BD as R&D Engine
- 72% of FDA approvals (2015-2021) required external innovation
- Three pillars: internal R&D, arm’s-length affiliates (Vividian), global co-labs + LEAPS VC
- Finerenone (Kerendia) — 25-year arc from molecule to HFpEF approval
- Asundexian — Factor XIa inhibitor; 26% stroke risk reduction (Phase 3)
- AI: Cradle collaboration; goal 40% productivity gain by 2030
Cross-Cutting Themes
- Elimination is the new modulation — durable control, potentially cure, requires eliminating pathogenic cells
- Causal human biology as north star — genetics, clinical experiments, not animal models alone
- AI most valuable where conventional approaches fail
- China’s R&D ecosystem already transforming competitive landscape
- Regulatory modernization is the highest-leverage policy intervention
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