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Alex Kesin and Matthew Pech

Approved

A Life Sciences , Science and Business podcast

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About the show

Life sciences, under the hood. Deep dives into the patent filings, regulatory gauntlets, and capital-risks that shape the business of biology.

Newest episodes

Allergan: Botox, Rogue Scientists, and the Ultimate Beauty Franchise

3 hr 36 min

Rate & Subscribe!!! The wild story of how a Cold War bioweapon became Botox — and how Allergan turned a sleepy ophthalmology drug into an enduring aesthetic franchise. Every part of this story looks nothing like your normal blockbuster drug. Botox started its development storyas a Cold War bioweapon so lethal the CIA was thinking of using it on Castro. Decades later, an eye surgeon in San Francisco mortgaged his house and managed to bootstrap his way to a BLA– no venture capital needed! After a contentious sale to a sleepy eye-drop company called Allergan, it turned Botox into one of the most durable, recurring-revenue franchises in the history of medicine.  That cash cow provoked all sorts of financial battles–  a hostile takeover attempt involving Bill Ackman, a tax-inversion scheme with Pfizer that united Bernie Sanders and Donald Trump in opposition, and a far-fetched plan to rent a Native American tribe's sovereign immunity to protect a different drug's patents. In this episode, we trace Botox from a 19th-century German sausage poisoning, through a Cold War weapons lab, an eye surgeon's garage-scale manufacturing operation, and into Allergan's decades-long reign — covering the science of why the drug still has no biosimilar, the "aesthetics stack" that turned it into a subscription business for faces, and the corporate finance drama (Valeant, Actavis, Pfizer and AbbVie) that followed. Along the way: exclusive interviews with Allergan's 95-year-old founding CEO, the scientist who helped manufacture the original drug substance in an academic lab, and the dermatologist who tried to repurpose Botox to treat depression. In this episode: How a Clostridium botulinum strain donated for free by a Harvard professor became the physical basis of a multi-billion-dollar drugWhy the FDA's insistence on unique nonproprietary names (onabotulinumtoxinA vs. abobotulinumtoxinA) created an accidental, unbreakable competitive moatHow Allergan built the "surround the ophthalmologist"...

What is Approved?

3 min

Approved tells the definitive stories behind the world's most interesting biotech ventures.  Most people learn about the industry in a fragmented, ad hoc way-- an industry article here, a clinical trial readout there, some science twitter.  In contrast, The Approved podcast tells comprehensive, definitive stories of how drugs are discovered, developed and sold. Whether we're tracking a single blockbuster drug's remarkable rise, or following a single startup’s decade-long path to approval, every episode we put out is an unvarnished look at how the biotech industry works. We break down what worked, what failed, and distill insights that you can apply to your own life science business. Every episode is accessible and entertaining, but ultimately designed for the life science professional.  Hosted by Matthew Pech, PhD (cancer biologist and drug hunter) and Alex Kesin (biotech writer), every episode draws on hundreds of hours of research -- including Nature papers, corporate decks, SEC filings, and legal records. All that is supplemented with original interviews with the actual scientists, operators, and clinicians who brought the drugs to life.  Season 1 Highlights Keytruda: Featuring conversations with Roy Baynes and Greg Carven.Blueprint Medicines: Featuring Christoph Lengauer and Alexis Borisy.Botox: Featuring Gavin Herbert Jr. and Brent Saunders.Season 1 is wrapping up soon, with our upcoming episode on a drug worth 285 million times its weight in gold (guesses are welcome). Research for Season 2 is already underway... Subscribe on Apple Podcasts and Spotify, or visit approved.fm.

Blueprint Medicines: Chasing Gleevec to a $9B Allergy Drug

2 hr 29 min

Blueprint Medicines was built to find the next Gleevec-style cancer drug. It ended up pivoting to allergic disease instead, and selling to Sanofi for $9B. This is the platform, the pivot, and who got paid. Blueprint Medicines set out to be the natural sequel to Gleevec: a company founded by two of the scientists behind that landmark cancer drug, built to order by Third Rock Ventures' "venture creation" model, with a proprietary kinase-inhibitor library designed to drug the 517 other broken molecular switches Gleevec couldn't touch. A decade later, Sanofi paid roughly $9 billion for the company... just not for a cancer drug. Blueprint's blockbuster asset, avapritinib (AYVAKIT), found its real market almost by accident: indolent systemic mastocytosis, a debilitating, often-undiagnosed mast-cell disease that took patients years to get diagnosed and had no approved treatment. In this episode, we trace two threads at once: the science of designing truly selective kinase inhibitors, and the venture capital philosophy -- company creation, not just company funding -- that built Blueprint from a whiteboard sketch into a platform biotech. We cover the near-death Series B, the accidental discovery that opened up mastocytosis, the GAVRETO partnership that fell apart against a faster competitor, the Sanofi negotiation (CVRs and all), and the wide gap between what the venture firm and hired executives made versus what the founding scientists -- like Gleevec's co-inventor Nick Lydon -- walked away with. We end covering the efforts of Blueprint diaspora to create a new model of seed investing: Curie Bio.  Featuring interviews with: Alexis Borisy: Former Blueprint CEO/Chairman; founding chairman, Curie.BioChristoph Lengauer: Founding CSO, Blueprint Medicines; Chief Drug Hunter, Curie.BioErica Evans: Former VP Biology, Blueprint Medicines; SVP, Curie.BioTim Guzi: Former Head of Medicinal Chemistry, Blueprint MedicinesDr. Charles Sawyers, M.D. — Academic co-founder, Blueprint Medicine...

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All episodes

Allergan: Botox, Rogue Scientists, and the Ultimate Beauty Franchise

3 hr 36 min

Rate & Subscribe!!! The wild story of how a Cold War bioweapon became Botox — and how Allergan turned a sleepy ophthalmology drug into an enduring aesthetic franchise. Every part of this story looks nothing like your normal blockbuster drug. Botox started its development storyas a Cold War bioweapon so lethal the CIA was thinking of using it on Castro. Decades later, an eye surgeon in San Francisco mortgaged his house and managed to bootstrap his way to a BLA– no venture capital needed! After a contentious sale to a sleepy eye-drop company called Allergan, it turned Botox into one of the most durable, recurring-revenue franchises in the history of medicine.  That cash cow provoked all sorts of financial battles–  a hostile takeover attempt involving Bill Ackman, a tax-inversion scheme with Pfizer that united Bernie Sanders and Donald Trump in opposition, and a far-fetched plan to rent a Native American tribe's sovereign immunity to protect a different drug's patents. In this episode, we trace Botox from a 19th-century German sausage poisoning, through a Cold War weapons lab, an eye surgeon's garage-scale manufacturing operation, and into Allergan's decades-long reign — covering the science of why the drug still has no biosimilar, the "aesthetics stack" that turned it into a subscription business for faces, and the corporate finance drama (Valeant, Actavis, Pfizer and AbbVie) that followed. Along the way: exclusive interviews with Allergan's 95-year-old founding CEO, the scientist who helped manufacture the original drug substance in an academic lab, and the dermatologist who tried to repurpose Botox to treat depression. In this episode: How a Clostridium botulinum strain donated for free by a Harvard professor became the physical basis of a multi-billion-dollar drugWhy the FDA's insistence on unique nonproprietary names (onabotulinumtoxinA vs. abobotulinumtoxinA) created an accidental, unbreakable competitive moatHow Allergan built the "surround the ophthalmologist"...

What is Approved?

3 min

Approved tells the definitive stories behind the world's most interesting biotech ventures.  Most people learn about the industry in a fragmented, ad hoc way-- an industry article here, a clinical trial readout there, some science twitter.  In contrast, The Approved podcast tells comprehensive, definitive stories of how drugs are discovered, developed and sold. Whether we're tracking a single blockbuster drug's remarkable rise, or following a single startup’s decade-long path to approval, every episode we put out is an unvarnished look at how the biotech industry works. We break down what worked, what failed, and distill insights that you can apply to your own life science business. Every episode is accessible and entertaining, but ultimately designed for the life science professional.  Hosted by Matthew Pech, PhD (cancer biologist and drug hunter) and Alex Kesin (biotech writer), every episode draws on hundreds of hours of research -- including Nature papers, corporate decks, SEC filings, and legal records. All that is supplemented with original interviews with the actual scientists, operators, and clinicians who brought the drugs to life.  Season 1 Highlights Keytruda: Featuring conversations with Roy Baynes and Greg Carven.Blueprint Medicines: Featuring Christoph Lengauer and Alexis Borisy.Botox: Featuring Gavin Herbert Jr. and Brent Saunders.Season 1 is wrapping up soon, with our upcoming episode on a drug worth 285 million times its weight in gold (guesses are welcome). Research for Season 2 is already underway... Subscribe on Apple Podcasts and Spotify, or visit approved.fm.

Blueprint Medicines: Chasing Gleevec to a $9B Allergy Drug

2 hr 29 min

Blueprint Medicines was built to find the next Gleevec-style cancer drug. It ended up pivoting to allergic disease instead, and selling to Sanofi for $9B. This is the platform, the pivot, and who got paid. Blueprint Medicines set out to be the natural sequel to Gleevec: a company founded by two of the scientists behind that landmark cancer drug, built to order by Third Rock Ventures' "venture creation" model, with a proprietary kinase-inhibitor library designed to drug the 517 other broken molecular switches Gleevec couldn't touch. A decade later, Sanofi paid roughly $9 billion for the company... just not for a cancer drug. Blueprint's blockbuster asset, avapritinib (AYVAKIT), found its real market almost by accident: indolent systemic mastocytosis, a debilitating, often-undiagnosed mast-cell disease that took patients years to get diagnosed and had no approved treatment. In this episode, we trace two threads at once: the science of designing truly selective kinase inhibitors, and the venture capital philosophy -- company creation, not just company funding -- that built Blueprint from a whiteboard sketch into a platform biotech. We cover the near-death Series B, the accidental discovery that opened up mastocytosis, the GAVRETO partnership that fell apart against a faster competitor, the Sanofi negotiation (CVRs and all), and the wide gap between what the venture firm and hired executives made versus what the founding scientists -- like Gleevec's co-inventor Nick Lydon -- walked away with. We end covering the efforts of Blueprint diaspora to create a new model of seed investing: Curie Bio.  Featuring interviews with: Alexis Borisy: Former Blueprint CEO/Chairman; founding chairman, Curie.BioChristoph Lengauer: Founding CSO, Blueprint Medicines; Chief Drug Hunter, Curie.BioErica Evans: Former VP Biology, Blueprint Medicines; SVP, Curie.BioTim Guzi: Former Head of Medicinal Chemistry, Blueprint MedicinesDr. Charles Sawyers, M.D. — Academic co-founder, Blueprint Medicine...

Keytruda: How Merck's Pembrolizumab Became the Best-Selling Cancer Drug of All Time

2 hr 7 min

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. 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: Sche...

Episode #2: Geron

2 hr 22 min

Listen on Spotify Listen on Apple Podcasts Listen on YouTube TABLE OF CONTENTS (00:00:00) - Introduction  (00:01:19) - Hayflick Limit  (00:08:30) - Michael West & Founding of Geron  (00:15:16) - Early Science & IP Strategy  (00:27:25) - Cloning the Telomerase Gene  (00:29:30) - Embryonic Stem Cells & Political Context  (00:44:21) - Okarma, West’s Departure & Corporate Turmoil  (01:05:08) - Spinal Cord Injury Trial  (01:30:45) - Pivot to Blood Cancer  (01:43:08) - Clinical & Commercial Drama (02:01:45) - Legacy & Lessons CREDITS Co-hosted by Alex Kesin and Matthew Pech Written, edited, and produced by Alex Kesin Music: “Food” by nerowski * Special thanks to the team at NFX for the use of their recording studio. SOURCES Last updated: March 2026 I. BOOKS Hall, Stephen S. Merchants of Immortality: Chasing the Dream of Human Life Extension. Houghton Mifflin, 2003. Williams, Tory. Inevitable Collision: The Inspiring Story That Brought Stem Cell Research to Conservative America.Mary Ann Liebert, Inc., 2014. II. KEY SCIENTIFIC PUBLICATIONS Hayflick, L. & Moorhead, P.S. “The serial cultivation of human diploid cell strains.” Experimental Cell Research 25 (1961): 585–621. Kim, N.W. et al. “Specific association of human telomerase activity with immortal cells and cancer.” Science 266, no. 5193 (1994): 2011–2015. Feng, J. et al. “The RNA component of human telomerase.” Science 269, no. 5228 (1995): 1236–1241. Nakamura, T.M. et al. “Telomerase catalytic subunit homologs from fission yeast and human.” Science 277, no. 5328 (1997): 955–959. Meyerson, M. et al. “hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization.” Cell 90, no. 4 (1997): 785–795. Bodnar, A.G. et al. “Extension of life-span by introduction of telomerase into normal human cells.” Science 279, no. 5349 (1998): 349–352. Thomson, J.A. et al. “Embryonic stem cell lines derived from human blastocysts.” Science 282, no. 5391 (1998): 1145–1147. Asai, A. et a...

Episode #1: Amylin Pharmaceuticals

1 hr 46 min

Listen on Spotify Listen on Apple Podcasts Listen on YouTube TABLE OF CONTENTS (00:00:00) - Introduction (00:04:40) - $50 of Dried Lizard Venom (00:29:17) - Fax of Death (00:43:04) - Sleeping Beauty Awakens (00:52:07) - Carl Icahn Sends a Letter (01:09:19) - Endgame (01:13:40) - Postmortem & Playbook CREDITS Co-hosted by Alex Kesin and Matthew Pech  Written, edited, and produced by Alex Kesin Music: “Food” by nerowski * Special thanks to the team at NFX for the use of their recording studio. SOURCES Last updated: January 2026 I. PRIMARY DOCUMENTS FDA Regulatory Documents Symlin (pramlintide acetate) - NDA 21-332 * Approval Letter & Package (March 16, 2005) * Medical Review * Statistical Review * Clinical Pharmacology & Biopharmaceutics Review * Administrative Documents & Correspondence Byetta (exenatide) - NDA 21-773 * Approval Letter & Package (April 28, 2005) * Medical Review * Statistical Review * Clinical Pharmacology & Biopharmaceutics Review * Administrative Documents & Correspondence Bydureon (exenatide ER) - NDA 22-200 * Approval Letter (January 27, 2012) * Other Action Letters (Complete Response) * Summary Review * REMS * Administrative Correspondence SEC Filings & Financial Documents * Amylin 2005 Results Press Release (Ex-99.1, 8-K) * Amylin 2007 Results Press Release (Ex-99.1) * Amylin 2011 Form 10-K (Net Product Sales) * Carl Icahn SEC Filing (Schedule 13D) Proxy Fight & Legal Documents * Carl Icahn Letter to Amylin (April 15, 2009) * Amylin Response to Icahn (April 20, 2009) * Police Fund v. Bradbury (Amylin) Trial (May 4, 2009) * Lilly Litigation Ruling (May 25, 2011) II. ORAL HISTORY & INTERVIEWS * Howard Greene Oral History (UCSD Library, October 8, 2008) - Primary source for Hybritech founding, Ted Greene’s background, and early Amylin history III. NEWS & TRADE PRESS 2000 * “The Rumsfeld Resume” - CBS News (December 28, 2000) - Donald Rumsfeld’s board tenure at Amylin (1991-1996) * “Roller Coasting” - Forbes (July 24, 2000) - Joe Cook narrative, J&...

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