Ep191: Emily Conley on Small Molecules to Correct a Rare Kidney Disease

Episode Summary

Executive Summary: Emily Conley, CEO of Renaissance Bio, discusses her path from neuroscience and 23andMe to leading a startup targeting autosomal dominant polycystic kidney disease (ADPKD). Renaissance is developing oral small-molecule correctors and potentiators aimed at restoring polycystin function, with the goal of delaying or preventing dialysis and transplant in a genetically validated, underserved kidney disease.

Main Topics: Conley’s personal and scientific path (Priority: 5/5): Her upbringing, family entrepreneurship example, and early exposure to autism, genetics, and neuroscience shaped her interest in biology and translational medicine. From academia to biotech industry (Priority: 5/5): At NIH and Stanford, Conley moved from basic neuroscience into a translational mindset, realizing she wanted to help turn science into therapies rather than stay in a narrow academic role. 23andMe as a formative company-building experience (Priority: 5/5): She joined early 23andMe, helped build neuroscience and therapeutics programs, and learned company scaling, regulatory complexity, and how genetic data can support drug discovery. Failure and lessons from Federation Bio (Priority: 4/5): As first-time CEO, she led a microbiome therapeutics company through an ambitious but ultimately underwhelming clinical result and wind-down, learning humility, execution discipline, and how to manage risk. Renaissance Bio’s ADPKD strategy (Priority: 5/5): The company is pursuing correctors and potentiators for polycystin mutations in ADPKD, using lessons from cystic fibrosis to target a validated disease mechanism across many mutations. Biomarkers, development strategy, and competition (Priority: 4/5): Renaissance aims to use MRI total kidney volume and urinary biomarkers to accelerate development, while competing with larger players such as Vertex and Regulus in a rapidly advancing kidney-disease space.

Key Arguments: Conley argues that translational biotech is where she can have the biggest impact because it connects scientific discovery directly to patients. She says 23andMe taught her that genetic data plus phenotype at scale can power therapeutic discovery and company building. She frames Federation Bio’s outcome as a scientific answer rather than a failure, emphasizing that drug development is inherently uncertain and humbling. Renaissance is pursuing ADPKD because the target is genetically validated, the unmet need is large, and the disease biology resembles cystic fibrosis in a way that may be therapeutically tractable. The company’s thesis is that a pan-mutant corrector/potentiator strategy can address many private mutations rather than being limited to a single subtype. Conley believes modern biomarkers and FDA receptivity to surrogate endpoints can make ADPKD drug development faster and more feasible than in the past. She argues that disease-modifying treatment could be relevant not only for advanced patients but potentially earlier in life, before irreversible kidney damage accumulates.

Data Points: ADPKD patient population in US and Europe: ~300,000 - Estimated number of patients mentioned as making the disease rare but not ultra-rare Kidney size in severe ADPKD: Up to 30 pounds per kidney - Describing how cyst burden can enlarge kidneys to a dysfunctional size 23andMe employees when Conley joined: 32 - Company size at the time she was hired 23andMe customers when Conley joined: 40,000 - Genomes in the database when she started 23andMe employees when Conley left: 600 - Company growth over her tenure 23andMe customers when Conley left: 10 million - Scale of the consumer genetics database by the end of her tenure Federation Bio timing: April 2020 - Conley joined as CEO during peak COVID Federation Bio trial scale: Over 100 strains - The synthetic microbiome consortia engineered for the program ADPKD genes: 2 major genes: PKD1 and PKD2 - Primary disease-causing genes encoding polycystins Mutation prevalence: No single mutation found in >2% of patients - Reason Renaissance is aiming for a pan-mutant approach CF comparator mutation: Delta F508 in 90% of patients - Used to contrast CF drug development with ADPKD heterogeneity Renascence funding round: $50M+ - Amount raised when the company came out of stealth in summer 2025 Clinical development window for TKV: 12 months - Total kidney volume can be measured over a year for accelerated approval discussions Regulus patient readout: Phase 1B - Referenced as a recent data point showing progress in the kidney-disease space Regulus genetic coverage: About 10% of patients - Vertex/Regulus-adjacent comparator mentioned for a narrower corrector Federation Bio shutdown context: 2022 - Biotech market downturn contributed to inability to raise additional capital Mayo clinic severity band: 1C to 1E - Likely clinical trial population for ADPKD progression studies Timeline to nominate DC: Next year or so - Renaissance’s plan for a development candidate nomination

Pivotal Quotes: "I realized that I wanted to do something that was more translational and that I wanted to, instead of just focusing very deeply on kind of a narrow question, that I wanted to focus more broadly." — Emily Conley: Explaining her shift from academic neuroscience toward biotech and drug development "We ask a scientific question and we got an answer, right? And that's drug development." — Emily Conley: Reflecting on Federation Bio’s disappointing clinical outcome and the lessons learned "If we go after the polycystin complex, then we really could change the course of the disease." — Emily Conley: Describing the core therapeutic rationale for Renaissance Bio’s ADPKD program

Implications: The conversation highlights ADPKD as an emerging therapeutic frontier with clearer biomarkers, validated biology, and room for first- and best-in-class drugs. For biotech, it shows how lessons from CF, genetics, and failed ventures can converge into a stronger development strategy.