Keytruda is Merck’s $31 billion a year PD-1 inhibitor and the best-selling cancer drug of all time. In Episode 3 of Approved, Alex Kesin and Matthew Pech trace the development of pembrolizumab , featuring interviews the scientists who drove the program forward : co-inventors Gregory Carven and Michel Streuli, and former Merck oncology CMO Roy Baynes.
Topics include preclinical PD1 / CTLA-4 checkpoint biology that brought industry attention to the target (Jim Allison’s CTLA-4 work and Tasuku Honjo’s PD-1 discovery); how pembro started as a failed rheumatoid arthritis antibody program at a Dutch subsidiary of a paint company; the two mega-mergers that nearly killed the program; the biomarker enrichment trial design behind KEYNOTE-024 that let Merck break BMS’s lead in lung cancer; the 41-patient Johns Hopkins MSI-H trial behind the first tissue-agnostic FDA approval, and the Jimmy Carter melanoma case that brought pembrolizumab to the public conscious. The episode closes on what comes next for Merck: the 2028 patent cliff, the Keytruda QLEX subcutaneous launch, and efforts to find the next blockbuster checkpoint inhibitor, including Summit/Akeso’s PD-1 / VEGF bispecific ivonescimab.
This episode is presented by JLL. Featuring Grant Dettmer on biotech real estate strategy.
CHAPTERS
00:00:00 — Introduction: The Best-Selling Cancer Drug of All Time
00:02:15 — Part One — A Century of Failed Cancer Immunotherapy
00:04:17 — T Cells, CD28, and the Two-Signal Model of Immune Activation
00:06:25 — Jim Allison’s CTLA-4 Discovery and the Path to Yervoy
00:12:03 — Tasuku Honjo Discovers PD-1: A Better Brake on T Cells
00:14:26 — Lieping Chen and the PD-L1 Tumor Evasion Hypothesis
00:16:26 — Part Two — Organon: The Dutch Paint-Company Subsidiary Behind Keytruda
00:19:48 — How Michel Streuli Caught the Solid-Phase Screening Artifact
00:22:09 — The Accidental Antagonist: From Rheumatoid Arthritis Drug to Cancer Drug
00:26:34 — Sponsor: Grant Detmer (JLL) on Biotech Real Estate Strategy
00:30:01 — Russian Nesting-Doll M&A: Schering-Plough Acquires Organon (2007)
00:31:43 — The $41 Billion Merck–Schering-Plough Mega-Merger of 2009
00:34:58 — Corporate Guerrilla Warfare: Four Scrappy Stunts That Saved Pembrolizumab
00:39:32 — BioNovion’s Spite-Company Bid to Buy Pembro Back
00:42:10 — BMS at ASCO 2010: The Data Print That Revived Merck’s PD-1 Program
00:45:55 — Part Three — Roger Perlmutter Joins a Bleeding Merck (April 2013)
00:50:48 — “Let Me Manage the Tigers”: Ken Frazier Backs the All-In Bet on Pembrolizumab
00:55:22 — Breakthrough Therapy Designation and Eric Rubin’s Adaptive Trial Design
00:58:25 — Keytruda’s 2014 FDA Approval Erases BMS’s Four-Year Lead
01:00:24 — The Lung Cancer Battlefield and the PD-L1 Biomarker Bet
01:02:19 — BMS vs. Merck: All-Comers vs. Biomarker-Enriched Trial Strategy
01:08:18 — KEYNOTE-024 vs. CheckMate-026: The Trial That Decided the Category
01:12:03 — Luis Diaz, MSI-H, and the Failed BMS Trial That Made Keytruda Tissue-Agnostic
01:17:18 — KEYNOTE-189: Perlmutter’s Bet on Combining Keytruda with Chemotherapy
01:19:21 — Merck’s Clinical Development Playbook: Basket Trials, Backwards March, External Collabs
01:25:29 — Part Four — The IO Graveyard: TIGIT, CD47, IDO1, LAG-3 and Tens of Billions Incinerated
01:30:23 — Why PD-1 Was the Only Checkpoint That Worked (Lieping Chen Revisited)
01:33:32 — Part Five — Inside the Best-Selling Drug of All Time
01:37:03 — “Build a Wall, High and Wide”: Merck’s Commercial Strategy for Keytruda
01:43:44 — Part Six — The Patent Cliff and Loss of Exclusivity in Pharma
01:45:35 — Keytruda QLEX (Subcutaneous) and the Lifecycle Management Playbook
01:50:23 — PD-1/VEGF Bispecifics: Ivonescimab, Summit Therapeutics, and the Next Threat
01:55:31 — The Scorecard: Patient, Academic, and Financial Impact
02:01:19 — Who Actually Profited: Merck vs. Organon vs. the Scientists Who Built the Drug
02:05:54 — Epilogue: The Jimmy Carter Drug
