Episode #1: Amylin Pharmaceuticals

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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

Figure 1: Amylin's pipeline timeline showing the "Sleeping Beauty" pivot. Symlin launch relegated to bottom with "pending FDA approval" while exenatide programs took priority. Source: 2004 ADA Presentation, slide 9.

Figure 2: Exenatide pivotal studies. The "3 AMIGOS" Phase 3 trial design. Source: 2004 ADA Presentation, slide 19.

Figure 3: The tolerability problem that haunted Byetta. 44% nausea rate in exenatide arm vs. 18% placebo. Source: 2004 ADA Presentation, slide 26.

Figure 4: The commercial slide Amylin ignored. “Less than 150 representatives can reach the MDs prescribing 40–50% of US insulin prescriptions.” Source: 2001 ADA Presentation, slide 18.

Figure 5: The market Amylin never captured. Twice-daily Byetta addressed ~1.3M patients; once-weekly dosing could reach 8–9M. Source: 2007 R&D Day, slide 14.

Figure 6: The trillion-dollar gap Amylin identified but never filled. Between Diet & Exercise (safe, ineffective) and Bariatric Surgery (effective, risky) lay the 10–15% weight loss zone where Wegovy and Zepbound now dominate. Source: 2007 R&D Day, slide 78.

Figure 7: Amylin's founding thesis. Peptide hormones as safer alternatives to small molecules with multiple organ effects and higher hit rates. Source: 2007 R&D Day, slide 29.

Figure 8: Phybrids Platform Amylin’s dual-agonist concept a decade before Mounjaro: fusing two hormones into a single molecule for synergistic effects. Source: 2006 R&D Day, slide 58.

Figure 9: Glucose-dependent Insulinotropic Polypeptide (GIP), Amylin was developing a second-generation GIP mimetic with extended half-life. Source: 2006 R&D Day, slide 43.

Figure 10: Incretin combos. More than a decade before Novo or Lilly, Amylin had preclinical data showing GLP-1 + 2nd gen GIP mimetic outperformed GLP-1 + native GIP. Source: 2006 R&D Day, slide 46.

Figure 11: Tirzepatide molecular structure. Its C-terminus (residues 30–39) derived directly from exenatide. In other words - Amylin's molecule is embedded in the world's best-selling drug. Credit: Oliver Philips.

IX. ANALYSIS FIGURES