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David Fagenbaum

2episodes
2podcasts

We have 2 summarized appearances for David Fagenbaum so far. Browse all podcasts to discover more episodes.

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2 episodes
Freakonomics Radio

664. Are Thousands of Medical Cures Hiding in Plain Sight?

Freakonomics Radio
52 minPhysician scientist, cofounder and president of EveryCure

AI Summary

→ WHAT IT COVERS Freakonomics Radio examines drug repurposing — using FDA-approved medications for new diseases — through physician-scientist David Fagenbaum's survival story, EveryCure's AI-driven platform scanning 4,000 drugs against 18,000 diseases, and economist Chris Snyder's pull-funding proposal to fix broken financial incentives blocking life-saving discoveries already sitting on pharmacy shelves. → KEY INSIGHTS - **The Repurposing Math:** Only 25% of the 18,000 known human diseases have FDA-approved treatments, yet repurposing existing drugs costs roughly 1% of developing a new compound from scratch. Generic drugs are already manufactured, safety-tested, and available at pharmacies, making them the highest-ROI path to closing the treatment gap for the remaining 13,500+ untreated diseases. - **AI Knowledge Graphs:** EveryCure's platform maps every drug, disease, gene, and protein into a biomedical knowledge graph, scoring all 4,000 approved drugs against all 18,000 diseases from 0 to 1. Scores near 0.99 flag the strongest repurposing candidates for human medical review, dramatically narrowing where researchers should focus clinical trial resources first. - **Lidocaine and Breast Cancer:** A 1,600-patient randomized trial published in the Journal of Clinical Oncology found that injecting lidocaine — a standard surgical numbing agent already used in nearly every procedure — around breast tumors eight to ten minutes before excision reduced patient mortality by 29%. Despite this result, no widespread adoption has occurred due to absent commercial incentives. - **Pull Funding Mechanism:** The Market Shaping Accelerator proposes a federal pull-funding program where Medicare or Medicaid pays companies a percentage of documented savings per patient after a repurposed generic drug proves effective. Estimated cost runs roughly $1 billion per successful indication, but government pays nothing unless measurable patient outcomes are confirmed first. - **Advanced Market Commitments Work:** The 2009 pneumococcal vaccine advanced market commitment — a $1.5 billion fund backed by the Gates Foundation and five governments — attracted three manufacturers, drove prices down, and has been credited with saving 700,000 children's lives. The same pull-funding model accelerated COVID-19 vaccine development, compressing a multi-year timeline into months. → NOTABLE MOMENT Fagenbaum discovered that rapamycin — the drug that saved his life — nearly never existed. The pharmaceutical company ordered it destroyed after it proved a poor antifungal. A researcher secretly stored it in his personal freezer until new management allowed further study, decades before Fagenbaum needed it. 💼 SPONSORS None detected 🏷️ Drug Repurposing, Market Incentives, AI Drug Discovery, Pull Funding, Rare Disease Treatment

Radiolab

The Medical Matchmaking Machine

Radiolab
62 minDoctor/Professor

AI Summary

→ WHAT IT COVERS Doctor David Fagenbaum survives five near-death relapses from rare Castleman disease by discovering rapamycin through self-experimentation, then builds AI system scoring 75 million drug-disease combinations to identify repurposing opportunities for all 18,000 known diseases. → KEY INSIGHTS - **Drug Repurposing Economics:** Twenty to thirty percent of all prescriptions written in the US are off-label because FDA approval locks drugs to specific diseases at fixed prices. Companies maximize profit on first approval, creating no financial incentive to study additional uses for generic medications. - **AI-Driven Medical Discovery:** Machine learning algorithms trained on thousands of known drug-disease relationships generate 75 million probability scores (0.01 to 0.99) ranking every FDA-approved drug against every disease. This identifies repurposing candidates humans cannot systematically evaluate, like sirolimus for Castleman disease or pembrolizumab for angiosarcoma. - **Biomedical Knowledge Graphs:** Mapping every gene, protein, pathway, and disease as connected nodes reveals treatment opportunities through shared biological mechanisms. Fagenbaum identified mTOR activation in his blood samples, traced connections to sirolimus (rapamycin), and achieved eleven-year remission after five near-fatal relapses. - **COVID Drug Success Model:** Dexamethasone and tocilizumab, both repurposed drugs, saved millions of lives during the pandemic. Dexamethasone was initially recommended against for COVID but reduced mortality by thirty-five percent when tested, demonstrating how systematic repurposing evaluation uncovers life-saving treatments faster than new drug development. - **Public Algorithm Release Strategy:** Every Cure will release their Matrix algorithm publicly within nine months, allowing researchers and physicians to access the same drug-disease probability scores the medical team uses. The tool generates research hypotheses requiring laboratory validation and clinical trials, not direct treatment recommendations for patients. → NOTABLE MOMENT Fagenbaum's uncle received a terminal angiosarcoma diagnosis with two months to live. Despite physician resistance, testing revealed ninety-nine percent of tumor cells expressed PD-L1. Pembrolizumab treatment achieved nine-year remission, and the approach became standard care without formal clinical trials. 💼 SPONSORS [{"name": "AT&T", "url": null}, {"name": "National Forest Foundation", "url": "https://nationalforest.org"}, {"name": "Genesis", "url": null}, {"name": "Fidelity", "url": "https://fidelity.com/baskets"}, {"name": "Lowe's", "url": "https://lowes.com/terms"}, {"name": "OMGES", "url": "https://omgs.com"}] 🏷️ Drug Repurposing, AI in Medicine, Castleman Disease, Rapamycin, Medical Innovation

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