→ WHAT IT COVERS Avalon Pharma CEO Lyn Baranowski explains how the company reformulates two approved oral pulmonary fibrosis drugs — pirfenidone and nintedanib — into inhaled versions delivered via handheld nebulizer, reducing doses by up to 97% while achieving 27x higher lung tissue exposure, targeting the 70% of IPF patients currently untreated due to intolerable side effects. → KEY INSIGHTS - **Oral drug tolerability gap:** Only 30% of the 300,000 annual U.S.
Latest Insights
Key takeaways from recent episodes
Ep206: Lyn Baranowski on Inhalable Medicines for Severe Lung Diseases
- ✓**Oral drug tolerability gap:** Only 30% of the 300,000 annual U.S. pulmonary fibrosis patients are on approved oral therapies at any given time, and just 10% remain on treatment across a full year. Pirfenidone causes severe nausea and vomiting; nintedanib causes debilitating diarrhea. This leaves a calculated addressable U.S. market of $42B annually — 300,000 patients at $150,000 per patient per year — almost entirely untapped.
- ✓**Inhaled dose reduction mechanics:** Reformulating pirfenidone for inhalation drops the daily dose from 2,400mg to 200mg — a 92% reduction. Inhaled nintedanib drops from 150mg to 4mg. Despite these reductions, lung tissue drug concentrations measured via bronchoalveolar lavage show 27x higher AUC exposure than oral delivery, because the drug is deposited directly into the alveoli rather than distributed systemically.
Ep205: Heather Turner on a Schizophrenia Drug Patients Can Stick With
- ✓**Blood-brain barrier modification:** Adding a single methyl group to amisulpride transforms a 50-country-approved antipsychotic into a once-daily compound with improved brain penetration. The methylation increases lipophilicity, enabling more efficient transport across the blood-brain barrier, reducing required doses, extending brain residence time, and opening a long-acting injectable formulation pathway — a meaningful adherence advantage in schizophrenia where staying on medication is the central clinical challenge.
- ✓**Placebo rate management in CNS trials:** Unlike metabolic trials where outcomes are objective measurements like body weight, neuropsychiatric trials rely on subjective symptom scales, making placebo response rates a primary execution risk. LB102's Phase 2 NOVA-1 trial achieved statistical significance across all three doses (50mg, 75mg, 100mg) partly by actively managing placebo inflation — a trial design discipline that Turner identifies as underappreciated before entering the CNS space.
Ep204: Troy Wilson on Precision Cancer Drugs and Combos
- ✓**Menin inhibitor mechanism:** Zifdomenib works by forcing leukemic blast cells to differentiate into normal cells rather than killing them directly. Those differentiated cells live a few weeks and die naturally. This mechanism produces deep responses and minimal toxicity, with differentiation syndrome as the primary risk — a side effect that largely disappears when zifdomenib is combined with chemotherapy, reducing the tumor burden before differentiation begins.
- ✓**AML market expansion path:** Kura's current FDA approval covers relapsed/refractory NPM1-mutant AML, a narrow initial indication. Two global Phase 3 trials enrolling approximately 1,300 patients target frontline AML combining zifdomenib with intensive chemotherapy. Phase 1 data presented at EHA Stockholm shows patients remaining disease-free at two years. Wilson projects peak U.S. revenues up to $3 billion annually if frontline approval covers roughly 50–60% of all AML patients.
Ep203: Sri Kosuri on Small Molecule Correctors of Disease
- ✓**Corrector drug strategy:** Protein misfolding and mistrafficking underlie a large proportion of rare diseases, cancers, and metabolic disorders because the most common way mutations disrupt protein function is by preventing proper folding or cellular localization. Octant targets this mechanism with oral small molecules, similar to how Vertex's Trikafta corrects CFTR misfolding in 90% of cystic fibrosis patients, opening a replicable template across multiple disease areas.
- ✓**Deep mutational scanning for patient stratification:** Octant builds every possible single amino acid mutation of a target gene in human cells, then runs trafficking or abundance assays to map which mutations cause misfolding. Cross-referencing this map against patient genetics allows the company to predict ahead of clinical trials exactly which mutations OCT-980 will rescue, enabling precise patient selection and informing the drug's eventual label.
Recent Episode Summaries
20 AI-powered summaries available
→ WHAT IT COVERS Heather Turner, CEO of LB Pharmaceuticals, traces her path from environmental law to biotech executive, culminating in Carmot Therapeutics' $2.7B Roche acquisition. She now leads LB Pharmaceuticals through late-stage development of LB102, a methylated amisulpride derivative targeting schizophrenia, bipolar depression, and adjunctive major depressive disorder.
→ WHAT IT COVERS Troy Wilson, cofounder and CEO of Kura Oncology, traces the path from a mediocre student in Palos Verdes to leading a company that achieved FDA approval in November 2025 for zifdomenib (COMZIFTI), a menin inhibitor for NPM1-mutant AML, while building a second program pairing farnesyltransferase inhibitor darlofarnib with RAS inhibitors for pancreatic cancer.
→ WHAT IT COVERS Sri Kosuri, cofounder and CEO of Octant Bio, describes how the company builds oral small molecule correctors targeting protein misfolding and mistrafficking across rare diseases, cancers, and metabolic disorders. Their lead compound OCT-980 entered phase one trials in March 2025 for rhodopsin-associated autosomal dominant retinitis pigmentosa, a progressive blindness condition affecting roughly 20,000 patients in the US and EU.
→ WHAT IT COVERS Becky Pferdehirt, CEO of Radial at the Astera Institute, explains how a $500M philanthropic commitment aims to fix structural failures across academia, industry, and venture capital by building open-source data infrastructure, rethinking publication incentives, and creating the data conditions necessary for AI to advance biological understanding.
→ WHAT IT COVERS Jeremy Levin, founder of Ovid Therapeutics and past BIO chairman, outlines why U.S. biotech faces a structural crisis of public distrust—tracing the decline from Martin Shkreli's 2015 price gouging through COVID vaccine backlash—and presents 10 concrete commitments companies can adopt to rebuild credibility and secure the industry's strategic future.
→ WHAT IT COVERS Richard Pops, 35-year CEO of Alkermes, discusses the company's late-stage development of elixirexant, an orexin-2 receptor agonist targeting narcolepsy type 1, with potential expansion into ADHD, MS fatigue, and Parkinson's. He also addresses mid-sized biopharma policy threats, including IRA pricing reforms, most-favored-nation pricing, and the rising competitive pressure from China.
→ WHAT IT COVERS University of Illinois chemistry professor Martin Burke explains how his block chemistry platform—using iterative carbon-carbon bond formation to synthesize small molecules modularly—enables full automation and AI integration. His startup Excelsior Sciences raised $95M to compress drug discovery cycle times from months to weeks, while his academic lab pursues antifungal and iron-transport therapeutics now in Phase 2 trials.
→ WHAT IT COVERS Abbas Kazimi, CEO of Nimbus Therapeutics, describes how a 70-person team with no labs used computational chemistry to discover zazositinib, a TYK2 inhibitor sold to Takeda for $4B upfront in 2022. He outlines the capital-efficient hub-and-spoke LLC model, target selection discipline, and culture that enabled two blockbuster exits across 17 years.
→ WHAT IT COVERS Viswa Colluru, founder and CEO of Envita, describes how he built a Boulder-based natural product drug discovery company from $55,000 in personal savings to a $1 billion valuation with $517 million raised, three candidates in clinical trials, and a platform that produces development candidates 4x faster than industry average with an 11x higher success rate.
→ WHAT IT COVERS Otello Stampacchia, founder of Omega Funds, outlines the structural and financial barriers holding back European biotech, where companies receive only 7% of global venture capital versus 63% for the US, and describes the European Life Sciences Coalition's advocacy strategy to mobilize capital, harmonize public markets, and accelerate clinical trial frameworks across the continent. → KEY INSIGHTS - **Capital allocation gap:** European pension funds invest approximately 0.
→ WHAT IT COVERS Ken Song, CEO of Candid Therapeutics, explains how bispecific T-cell engaging antibodies could deliver CAR-T-like immune resets for autoimmune diseases at scale. The San Diego startup raised $370M, licensed two clinical-stage assets from China, and has now treated over 60 autoimmune patients across 10 disease indications in under 18 months.
→ WHAT IT COVERS Stanford immunologist and physician-scientist Ansu Satpathy discusses how single-cell genomics and multi-omic tools are reshaping cancer immunotherapy and autoimmune drug discovery. He covers his path from Midwest public schools through MD-PhD training to founding Cartography Biosciences, Santa Ana Bio, and Immuni, while arguing US academic innovation still outpaces Chinese biotech pipelines in breakthrough potential.
→ WHAT IT COVERS Ron Renaud, CEO of Kailera Therapeutics, explains how his company is building a GLP-1 obesity drug portfolio around licensed assets from China's Jiangsu Hengrui Pharmaceuticals. With $1 billion raised and Phase 3 trials underway, Kailera's lead injectable candidate targets patients with BMI above 35, aiming for best-in-class weight loss by 2029.
→ WHAT IT COVERS Kate Haviland, former CEO of Blueprint Medicines, traces the company's evolution from a precision oncology startup to a precision immunology leader, culminating in Sanofi's $9.1 billion acquisition in 2025. The episode covers how Blueprint pivoted from rare cancers to systemic mastocytosis, achieving 75-80% response rates and building a commercially durable franchise.
→ WHAT IT COVERS Emily Conley, CEO of Renaissance Bio, explains how the company is developing oral small molecule correctors and potentiators to treat autosomal dominant polycystic kidney disease (ADPKD), a genetic condition affecting 300,000 patients in the US and Europe, by targeting the polycystin protein complex using a framework borrowed from cystic fibrosis drug development.
→ WHAT IT COVERS Neil Kumar, founder and CEO of BridgeBio Pharma, details how he built a rare disease drug company using a hub-and-spoke portfolio model starting in 2015 with $7M. The company now has one blockbuster drug generating $108M in a single quarter, with two additional programs showing strong phase three clinical results. → KEY INSIGHTS - **Hub-and-Spoke Portfolio Design:** BridgeBio structures each drug program as a separate subsidiary with its own focused disease team, while...
→ WHAT IT COVERS Marc Tessier-Lavigne, CEO of Xaira Therapeutics, outlines how the South San Francisco startup deploys AI across all three stages of drug discovery — target identification, molecular design, and patient matching — backed by $1 billion in committed capital and Nobel laureate David Baker's protein design technology, with the goal of halving drug development timelines from 13 to 6.5 years.
→ WHAT IT COVERS Art Krieg, founder of Zola Therapeutics and pioneer of CpG DNA immunotherapy, explains how his new oligonucleotide drug candidate simultaneously activates TLR7, TLR8, and TLR9 receptors to mimic a retroviral infection signal, potentially converting immune-suppressive tumor environments into active cancer-killing responses across multiple solid tumor types.
→ WHAT IT COVERS Eric Fischer, structural biologist at Dana-Farber Cancer Institute, explains how targeted protein degraders and molecular glues work as a new drug class, tracing the field from thalidomide's rediscovered mechanism through the 2014 breakthrough papers, the $80M Deerfield-Dana-Farber Center for Protein Degradation, and spinout companies including Neomorph now partnered with Novartis, Biogen, and AbbVie.
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Resources mentioned on The Long Run with Luke Timmerman
Books, tools, and gear cited by guests across episodes we've summarized.
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AlphaSense
by AlphaSense
Cited in 3 episodes of The Long Run with Luke Timmerman
- tool
Dash Bio
Cited in 3 episodes of The Long Run with Luke Timmerman
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AlphaFold
Cited in 2 episodes of The Long Run with Luke Timmerman
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DASH
by DASH
Cited in 2 episodes of The Long Run with Luke Timmerman
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Alnylam
Cited in 1 episode of The Long Run with Luke Timmerman
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scGPT
Cited in 1 episode of The Long Run with Luke Timmerman
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OCT-980
by Octant Bio
Cited in 1 episode of The Long Run with Luke Timmerman
- product
venetoclax
Cited in 1 episode of The Long Run with Luke Timmerman
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