Approved

Alex Kesin and Matthew Pech

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

Episodes

  1. 1 HR AGO

    Episode #2: Geron

    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 al. “A novel telomerase template antagonist (GRN163) as a potential anticancer agent.” Cancer Research 63, no. 14 (2003): 3931–3939. Herbert, B-S et al. “Effect of the lipid modification of GRN163.” Nature: Oncogene 24 (2005): 5765–5772. Baerlochr, G. et al. “A pilot study of the telomerase inhibitor imetelstat for myelofibrosis.” New England Journal of Medicine 373 (2015): 908–919. Platzbecker, U. et al. “Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge).” The Lancet (2024). Lennox, A.L et al. “Imetelstat, a novel, first-in-class telomerase inhibitor: Mechanism of action, clinical, and translational science.” Clinical and Translational Science 17, no. 11 (2024). Scott, C. & Magnus, D. “Wrongful Termination: Lessons From the Geron Clinical Trial” Stem Cell Reports 3, no. 5 (2014): 721–723. III. REGULATORY & CLINICAL Prescribing Information (Label) U.S. Food and Drug Administration. “RYTELO (imetelstat) for injection: Highlights of Prescribing Information.” NDA 217779. June 2024. NDA Approval Letter U.S. Food and Drug Administration. “NDA Approval Letter: RYTELO (imetelstat) for injection.” NDA 217779. June 6, 2024. Multi-Discipline Review & Evaluation U.S. Food and Drug Administration. “NDA Multi-Disciplinary Review and Evaluation: RYTELO (imetelstat).” NDA 217779Orig1s000. 2024. ODAC Briefing Document U.S. Food and Drug Administration. “FDA Briefing Document: Oncologic Drugs Advisory Committee Meeting, NDA 217779, Imetelstat.” March 14, 2024. REMS/Risk Assessment Review U.S. Food and Drug Administration. “Risk Assessment and Risk Mitigation Review: RYTELO (imetelstat).” NDA 217779Orig1s000. 2024. Kim, N. et al. “US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia.” The Oncologist (2025). PMID: 41135032. FDA. “FDA Approves Imetelstat for Low- to Intermediate-1-Risk Myelodysplastic Syndromes with Transfusion-Dependent Anemia.” June 2024. ICER. “Evidence Report: Treatment for Anemia in Myelodysplastic Syndrome.” August 2024. ICER. Press Release on Imetelstat Evidence Assessment. ClinicalTrials.gov. GRNOPC1 Phase I Trial. NCT01217008. Myelodysplastic Syndrome Epidemiology. PMC4553145. MDS Risk and AML Progression. Blood (2023). IV. CORPORATE FILINGS & PRESENTATIONS Geron Corporation. S-1 Registration Statement (1996 IPO). Geron Corporation. Corporate presentations archive (2012–present). Geron Corporation. 2012 R&D Strategy Presentation. Geron Corporation. 2013 NSCLC Study Results. Geron Corporation. 2015 Janssen/MF Collaboration Presentation. (p.41-) Geron Corporation. 2016 Mechanism of Action Analysis (thrombocytopenia/TLR9). Royalty Pharma. “Royalty Pharma to Acquire Royalty Interest in Geron’s Rytelo for $125 Million.” November 2024. V. NEWS & MEDIA COVERAGE [1994] New York Times. “Immortality Enzyme Is Discovered in Many Types of Cancer.” December 27, 1994. [1995] New York Times. “New Light Shed on How Enzyme May Play Crucial Role in Cancer.” September 5, 1995. [1996] New Yorker. “The New Age of Man.” September 30, 1996. [1996] Bio.net Ageing Forum. Geron financing announcements. [1996] Bio.net Ageing Forum. Geron NCI/SBIR grants. [1996] Bio.net Ageing Forum. Kyowa Hakko deal. [1996] Bio.net Ageing Forum. Kyowa Hakko deal details. [1996] BioWorld. Geron IPO news. [1998] ScienceDaily. “Human Embryonic Stem Cells Successfully Derived.” November 9, 1998. [1998] New York Times. “Scientists Cultivate Cells at Root of Human Life.” November 6, 1998. [1998] New York Times. “Essay: Immortality, of a Sort, Beckons to Biologists.” November 17, 1998. [1999] Dooling, Richard. “Diary of an Immortal Man.” Published on KurzweilAI.net, May 1999. [2000] Wired. “Embryonic Cell Debate Is On.” August 2000. [2001] New York Times. “Public Lives: Cell Biologist Traded Religious Fervor for Scientific Zeal.” August 13, 2001 [2001] WARF. “WARF Amends Stem Cell Suit.” [2001] USCCB. “Human Embryo Research Is Illegal, Immoral, and Unnecessary.” [2002] Forbes. Stem cell coverage, January 31, 2002. [2004] Nature Reviews - Telomere biology and cancer. [2004] New York Times. “Cloning, Stem Cells: Medical and Ethical Issues Cloud Cloning for Therapy.” February 13, 2004. [2004] Seattle University School of Law. “Geron and stem cell ethics.” [2005] PharmaTimes. “Geron Leaps on Merck Deal.” [2008] Gitschier, J. “Interview with James Thomson.” PLoS Genetics (2008). [2010] New York Times. A First For Stem Cell Use In Therapy. October 11, 2010. [2011] Forbes (Matthew Herper). “Stem Cell Innovator James Thomson Says Geron Blazed Trail.” November 15, 2011. [2011] Washington Post. “First Patient to Get Stem Cell Therapy Is Identified.” April 2, 2011. [2011] Washington Post. “Stem Cells Were God’s Will, Says First Recipient of Treatment.” April 14, 2011. [2011] New York Times. Michael West / BioTime profile. May 19, 2011. [2011] New York Times. “Geron Is Shutting Down Its Stem Cell Clinical Trial.” November 15, 2011. [2011] The Guardian. “Geron Abandons Stem Cell Therapy.” November 15, 2011. [2011] Science. “Geron Bails Out of Stem Cells.” [2011] The Hastings Center. “Geron’s Discontinued Stem Cell Trial: What About the Research Participants?” [2011] CIRM. “Geron Discontinues Stem Cell Program.” November 14, 2011. [2013] The Scientist. “Geron’s Stem Cell Program Sold.” (Asterias/BioTime acquisition). [2013] The Niche (Paul Knoepfler). Interview with BioTime CEO Michael West, Part 1. [2013] The Niche. Interview with Mike West, Part 2: Geron hESC. [2013] The Niche. Interview with Mike West, Part 3: Key Flaw in Stem Cell Field. [2013] The Niche. “BioTime Subsidiary Asterias Acquires Geron Embryonic Stem Cell Program.” [2013] Nature Medicine. “No End in Sight for Telomerase-Targeted Cancer Drugs.” January 2013. [2016] USC Health Sciences. Kris Boesen stem cell recovery. [2016] The Niche. “Asterias Interview: Stem Cell Spinal Cord Injury Trials Advance.” December 2016. [2018] FierceBiotech. “Geron Craters as Janssen Bows Out of Imetelstat Pact Once Worth Up to $935M.” September 2018. [2018] STAT News (Adam Feuerstein). “Geron Warning Signs.” September 27, 2018. [2018] GlobeNewsWire. “Asterias Provides Update for AST-OPC1 Phase 1/2a Clinical Trial.” February 28, 2018. [2023] Pharmaphorum. “Geron Finally Gets Close to a Product Approval with Imetelstat.” [2023] STAT News. “Geron Success in Myelodysplastic Syndromes.” January 4, 2023. [2024] Reuters. “US FDA Staff Flags Concerns About Geron’s Anemia Treatment.” March 12, 2024. [2024] BioPharma Dive. “Geron Approval, Blood Disorder, Nobel Prize, Imetelstat.” [2024] STAT News. “I Was Wrong About Geron’s Blood Cancer Drug. Now, Is It a Takeover Target?” March 18, 2024. [2024] CIRM Blog. “Where Are They Now: Jake Javier.” August 19, 2024. [2024] Christopher Reeve Foundation. “Pioneering Cell Transplants for the Treatment of SCI.” [2024] Oncology Pipeline / ApexOnco. “Seven Problems Geron.” [2024] AInvest. “Geron Navigating Legal Headwinds, Rytelo Commercial Crossroads.” [2025] BiotechNation. “No More Transfusions: Dr. John Scarlett, CEO of Geron Corporation.” [2025] PharmaVoice. “Geron’s Harout Semerjian on Drug Approval and Pharma.” [2025] Investing.com. “Geron at Stifel 2025 Healthcare Conference: Strategic Adjustments for Rytelo.” [2025] SFGate. “Geron Lays Off Third of Staff.” [2025] Fierce Pharma. “Geron to Lay Off 13% of Workforce to Slash Operating Costs.” [2025] PharmaTimes. PCSK9 inhibitor launch comparison. https://pharmatimes.com/web_exclusives/are

    2h 22m
  2. 30 JAN

    Episode #1: Amylin Pharmaceuticals

    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&J partnership collapse 2005 * “Investing for a Profit and a Daughter’s Health” - NYT (March 19, 2005) - Allen Andersson investment story, “tablecloth deal” 2006 * “Diabetics see hope (and weight loss) in new drug” - NYT (March 2, 2006) - “Lizzie” nickname, patient testimonials * “4 Diabetes Drugs Are Seen Raising Hope and Profit” - NYT (June 22, 2006) - Manufacturing shortage, 400,000+ patients * “Don’t kill off life-saving drugs” - Heritage Foundation (August 15, 2006) - Policy perspective on Byetta’s potential impact * “Byetta Craze Is First Salvo in Promising New Line of Drugs” - diaTribe - ADA conference chaos, “one man cried” 2007 * Dr. John Eng Profile - Diabetes In Control (September 18, 2007) - Eng’s discovery story, patent struggles, Amylin vs. Lilly negotiations 2008 * Xenome/Amylin Partnership - BioSpace (February 5, 2008) - Venom peptide library partnership 2009 * Eastbourne Capital Sells Stake - San Diego Union-Tribune (October 10, 2009) - End of Eastbourne activist campaign * Survey: Additional Diabetes Drugs Needed - Cardiovascular Business (December 21, 2009) - Market research on GLP-1 adoption 2012 * “FDA review accuses Amylin of withholding data” - FierceBiotech (June 26, 2012) - Bydureon approval controversy IV. ACADEMIC & SCIENTIFIC SOURCES * “Structural insights into multiplexed pharmacological actions of tirzepatide...” - Nature Communications (February 25, 2022) - Tirzepatide structure, exenatide C-terminus connection * “Structural and dynamic features of cagrilintide binding...” - Nature Communications (April 10, 2025) - Cagrilintide/pramlintide structural relationship * “If You Poison Us Do We Not Die?” - BYU Law Review (May 1, 2010) - Legal analysis of poison put provisions * “How GLP-1 Receptor Agonists Evolved from Diabetes to Weight Loss Treatments” - Historical overview of GLP-1 development V. HARVARD BUSINESS SCHOOL CASES * “Amylin Pharmaceuticals: Diabetes and Beyond” (December 9, 2008) - Authors: Richard G. Hamermesh, Rachel Gordon * “Amylin Pharmaceuticals: Diabetes and Beyond” (November 2, 2012 revision) - Authors: Richard G. Hamermesh, Carin-Isabel Knoop VI. CORPORATE DOCUMENTS & PRESENTATIONS Amylin investor presentations from corporate IR archives. Specific slides referenced in the script are noted below. Investor Presentations (Full Decks) * 2006 R&D Day Presentation (PDF) - Phybrids platform, GIP mimetic program (slides 43, 46, 58-59) * 2007 R&D Day Presentation (PDF) - Market sizing, obesity portfolio positioning (slides 14, 28, 29, 78) * 2007 J.P. Morgan Healthcare Conference (PDF) - Symlin Pen timeline (slide 25) * 2007 Lehman Brothers Healthcare Conference (PDF) - Investor overview and pipeline update Individual Slide Presentations (HTML Archives) * Early Corporate Presentation (WFVK) - Early-era company overview * 2003 Headquarters Presentation - January 2003 corporate update * ADA IR Presentation - American Diabetes Association investor materials VII. ADDITIONAL REFERENCES * Encyclopedia.com: Amylin Pharmaceuticals, Inc. * Miami Serpentarium Laboratories (Gila monster venom source) * Dan Bradbury (former Amylin CEO) - Vivani Board Profile - Now developing exenatide implant for weight loss * Full-year 2008 results - FierceBiotech VIII. PRIMARY SOURCE FIGURES IX. ANALYSIS FIGURES This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit www.approved.fm

    1h 46m

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

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