EP 212: A hub-and-spoke model for accelerating rare disease drug development with Ananth Sridhar and Sun-Gou Ji of BridgeBio
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 Podcast00:59 Welcome to Ananth & Sun-Gou01:57 How BridgeBio’s hub-and-spoke model de-risks and accelerates rare disease drug development06:45 How programs move from the hub to the spokes in target discovery and development09:10 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 variants18:08 Under-diagnosis and incomplete penetrance in rare disease and quantifying genetic versus phenotypic prevalence20:52 Balancing first-in-class innovation with risk management in rare disease drug development24:24 Evaluating rare disease programs using risk-adjusted net present value (NPV) instead of peak sales27:20 Key factors that can make rare disease programs faster and cheaper to develop, and why modality agnosticism is important32:00 Sun-Gou’s experience in computational genetics and building data-driven infrastructure for discovery36:44 Ananth’s lessons from Regeneron and applying patient-centered principles to rare disease drug development39:00 Sun-Gou on the power of newborn sequencing and personal lessons from early diagnosis43:36 Ananth’s views on making predictive medicine more personal and human-centered44:51 Closing remarksFind out moreBridgeBio (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)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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EP 211: Building hope for inherited blindness and deafness with Justin Porcano of Save Sight Now
Summary: This week on The Genetics Podcast, Patrick is joined by Justin Porcano, co-founder and Executive Director of Save Sight Now. They discuss how his daughter’s diagnosis with Usher syndrome type 1B (USH1B) inspired the founding of Save Sight Now, the organization’s efforts to accelerate research and overcome barriers in gene therapy, and the innovative gene delivery methods and therapeutic approaches currently in development.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Justin01:39 How Justin’s daughter’s Usher syndrome diagnosis (USH1B) led to the founding of Safe Sight Now and a mission to accelerate research05:23 Biggest hurdles to therapeutic development for USH1B08:36 Progress in the research with new animal models and advances in clinical endpoint development10:25 How Justin applied design thinking and AI to rapidly learn rare disease science12:38 Advances in gene delivery approaches for USH1B15:45 Therapeutic intervention windows in USH1B with early treatment for hearing loss and later options for addressing vestibular and visual impairments18:32 Save Sight Now’s plans for the next phase of clinical translation and sustainable growth20:50 Why Justin decided to establish Save Sight Now as an independent nonprofit22:27 The need for stronger collaboration between patient organizations and biotech companies25:50 Building global collaborations to expand Save Sight Now’s reach28:00 How the community can support Save Sight Now’s mission and upcoming fundraising gala28:59 Closing remarksFind out moreSave Sight Now (https://www.savesightnow.org/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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EP 210: Live from ASHG: Breaking barriers in genomics with Heidi Rehm of the Broad Institute and Slavé Petrovski of AstraZeneca
Summary: This week on The Genetics Podcast, recorded live at ASHG 2025, Patrick is joined by Heidi Rehm, Chief Genomics Officer at MGH’s Center for Genomic Medicine and Co-director at the Broad Institute, and Slavé Petrovski, Vice President of AstraZeneca's Centre for Genomics Research. They discuss the rapid progress of large-scale genomics, the barriers to integrating genetic data into healthcare and drug development, and how open collaboration, global data sharing, and a focus on equity are driving more inclusive and impactful genomic discovery.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Heidi and Slavé02:01 Slavé’s role at AstraZeneca and work in genomics-driven R&D 03:24 Heidi’s work at the Broad Institute bridging clinical genomics, rare disease research, and global data-sharing initiatives04:12 Heidi on breaking a Guinness world record for rapid neonatal ICU (NICU) genomics and the shift to open data sharing06:32 Slavé on how large-scale, multimodal human data is transforming genomics research08:10 Heidi’s initiatives to integrate genomics into routine care at hospitals and with primary care physicians11:47 Integrating genomics into clinical trials and healthcare, and enabling global discovery through AstraZeneca’s open data portal15:34 Breaking down legal and logistical barriers to genomic data sharing and centering the patient voice18:40 AstraZeneca’s large-scale plasma proteome study and machine learning models predicting disease onset years before diagnosis21:44 Emerging omics tools advancing rare disease diagnosis24:19 The value and pitfalls of AI in genomics today28:54 Advancing health equity in genomics through data sharing, diverse recruitment, and global collaboration33:40 Progress and challenges in next-generation genetic therapies37:15 Reflections and advice for the next generation entering genomics and data-driven medicine40:44 Audience Q&A51:44 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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EP 209: Reinventing Fabry disease treatment with Chris Hopkins of Glafabra Therapeutics
This week on The Genetics Podcast, Patrick is joined by Chris Hopkins, CEO of Glafabra Therapeutics. They discuss how Glafabra is advancing a next-generation cell therapy for Fabry disease, the differences between gene therapy modalities, and the future of cell and gene therapy innovation.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Chris01:28 Overview of Fabry disease and reviving a promising shelved gene therapy03:12 Limitations of current Fabry disease treatments versus Glafabra Therapeutics’ approach05:19 How autologous cell therapy avoids an immune response06:43 Comparing this cell therapy approach to that of Casgevy for sickle cell disease11:28 Expanding Glafabra’s platform to other lysosomal storage disorders through enzyme cross-correction13:47 Comparing autologous cell therapy and AAV in Fabry17:02 Path to clinical development and funding strategy for Glafabra’s lead program19:33 Cost efficiency and trial design advantages of an orphan drug approach21:19 Considerations around comparator groups for Glafabra’s therapy24:11 Underdiagnosis and hidden prevalence of rare diseases 25:53 Other innovations Chris is excited about and expectations for the future of cell and gene therapy31:56 How Chris invented a technique to safely “milk” venomous cone snails37:00 Closing remarks and advice for scientists taking the leap from academia to entrepreneurshipFind out moreGlafabra Therapeutics (https://www.glafabra.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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EP 208: Gene therapy at a crossroads: Successes, concerns, and the path forward
Summary: This week on The Genetics Podcast, Patrick Short takes a solo deep dive into the current state of gene therapy ahead of next week’s live recording at ASHG. He explores the promise and limitations of adeno-associated virus (AAV) delivery, examples of gene therapies for neuromuscular diseases, and the challenges of balancing safety, cost, and commercial viability in rare diseases. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Episode overview02:50 Definition and scope of gene therapy 04:50 Gene therapy delivery via adeno-associated virus (AAV) and associated challenges and advantages06:40 AAV-based gene therapy and other advanced therapies in spinal muscular atrophy (SMA)10:29 Recent safety concerns around Sarepta Therapeutics’ AAV-based gene therapy for Duchenne muscular dystrophy (DMD)19:30 Commercial viability challenges for rare disease gene therapy24:26 Risk-benefit analysis of gene therapy for rare diseases 28:33 Considerations for optimizing AAV design and delivery routes31:26 Alternative approaches for delivery using viral and non-viral methods36:09 The future of AAV gene therapy41:42 Closing remarksFind out moreUpdate on Sarepta Therapeutics’ gene therapy for DMD (https://www.fiercepharma.com/pharma/sarepta-shares-more-elevidys-safety-data-response-patient-group-fda-petition)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
Exploring all things genetics. Dr Patrick Short, University of Cambridge alumnus and CEO of Sano Genetics, analyses the science, interviews the experts, and discusses the latest findings and breakthroughs in genetic research. To find out more about Sano Genetics and its mission to accelerate the future of precision medicine visit: www.sanogenetics.com
Ireland