Summary: 

This week on The Genetics Podcast, Patrick is joined by BridgeBio’s Ananth Sridhar, Chief Operating Officer of Cardiorenal Programs, and Sun-Gou Ji, Vice President of Computational Genomics. They discuss the hub-and-spoke model for de-risking and accelerating rare disease drug development, the role of human genetics in target discovery, lessons from their autosomal dominant hypocalcemia type 1 (ADH1) program, and how portfolio design and predictive genomics are shaping the future of precision medicine.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Ananth & Sun-Gou

01:57 How BridgeBio’s hub-and-spoke model de-risks and accelerates rare disease drug development

06:45 How programs move from the hub to the spokes in target discovery and development

09:10 Translating a target into a therapy for autosomal dominant hypocalcemia type 1 (ADH1)

12:28 Challenges in ADH1 drug development and using population genetics to identify patients with gain-of-function variants

18:08 Under-diagnosis and incomplete penetrance in rare disease and quantifying genetic versus phenotypic prevalence

20:52 Balancing first-in-class innovation with risk management in rare disease drug development

24:24 Evaluating rare disease programs using risk-adjusted net present value (NPV) instead of peak sales

27:20 Key factors that can make rare disease programs faster and cheaper to develop, and why modality agnosticism is important

32:00 Sun-Gou’s experience in computational genetics and building data-driven infrastructure for discovery

36:44 Ananth’s lessons from Regeneron and applying patient-centered principles to rare disease drug development

39:00 Sun-Gou on the power of newborn sequencing and personal lessons from early diagnosis

43:36 Ananth’s views on making predictive medicine more personal and human-centered

44:51 Closing remarks

Find out more

• BridgeBio (https://bridgebio.com/unlocking-rare-diseases-medicine)

• Hub-and-spoke model (https://www.youtube.com/watch?v=gRURL49QsX4)

• ADH1 publication (https://www.cell.com/ajhg/fulltext/S0002-9297(25)00244-7)

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