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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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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 Podcast
00:59 Welcome to Justin
01:39 How Justin’s daughter’s Usher syndrome diagnosis (USH1B) led to the founding of Safe Sight Now and a mission to accelerate research
05:23 Biggest hurdles to therapeutic development for USH1B
08:36 Progress in the research with new animal models and advances in clinical endpoint development
10:25 How Justin applied design thinking and AI to rapidly learn rare disease science
12:38 Advances in gene delivery approaches for USH1B
15:45 Therapeutic intervention windows in USH1B with early treatment for hearing loss and later options for addressing vestibular and visual impairments
18:32 Save Sight Now’s plans for the next phase of clinical translation and sustainable growth
20:50 Why Justin decided to establish Save Sight Now as an independent nonprofit
22:27 The need for stronger collaboration between patient organizations and biotech companies
25:50 Building global collaborations to expand Save Sight Now’s reach
28:00 How the community can support Save Sight Now’s mission and upcoming fundraising gala
28:59 Closing remarks
Find out more
Save 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
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 Podcast
00:59 Welcome to Heidi and Slavé
02:01 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 initiatives
04:12 Heidi on breaking a Guinness world record for rapid neonatal ICU (NICU) genomics and the shift to open data sharing
06:32 Slavé on how large-scale, multimodal human data is transforming genomics research
08:10 Heidi’s initiatives to integrate genomics into routine care at hospitals and with primary care physicians
11:47 Integrating genomics into clinical trials and healthcare, and enabling global discovery through AstraZeneca’s open data portal
15:34 Breaking down legal and logistical barriers to genomic data sharing and centering the patient voice
18:40 AstraZeneca’s large-scale plasma proteome study and machine learning models predicting disease onset years before diagnosis
21:44 Emerging omics tools advancing rare disease diagnosis
24:19 The value and pitfalls of AI in genomics today
28:54 Advancing health equity in genomics through data sharing, diverse recruitment, and global collaboration
33:40 Progress and challenges in next-generation genetic therapies
37:15 Reflections and advice for the next generation entering genomics and data-driven medicine
40:44 Audience Q&A
51:44 Closing remarks
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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 Podcast
00:59 Welcome to Chris
01:28 Overview of Fabry disease and reviving a promising shelved gene therapy
03:12 Limitations of current Fabry disease treatments versus Glafabra Therapeutics’ approach
05:19 How autologous cell therapy avoids an immune response
06:43 Comparing this cell therapy approach to that of Casgevy for sickle cell disease
11:28 Expanding Glafabra’s platform to other lysosomal storage disorders through enzyme cross-correction
13:47 Comparing autologous cell therapy and AAV in Fabry
17:02 Path to clinical development and funding strategy for Glafabra’s lead program
19:33 Cost efficiency and trial design advantages of an orphan drug approach
21:19 Considerations around comparator groups for Glafabra’s therapy
24:11 Underdiagnosis and hidden prevalence of rare diseases
25:53 Other innovations Chris is excited about and expectations for the future of cell and gene therapy
31:56 How Chris invented a technique to safely “milk” venomous cone snails
37:00 Closing remarks and advice for scientists taking the leap from academia to entrepreneurship
Find out more
Glafabra 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
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 Podcast
00:59 Episode overview
02:50 Definition and scope of gene therapy
04:50 Gene therapy delivery via adeno-associated virus (AAV) and associated challenges and advantages
06:40 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 therapy
24:26 Risk-benefit analysis of gene therapy for rare diseases
28:33 Considerations for optimizing AAV design and delivery routes
31:26 Alternative approaches for delivery using viral and non-viral methods
36:09 The future of AAV gene therapy
41:42 Closing remarks
Find out more
Update on Sarepta Therapeutics’ gene therapy for DMD (https://www.fiercepharma.com/pharma/sarepta-shares-more-elevidys-safety-data-response-patient-group-fda-petition)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
Summary:
This week on The Genetics Podcast, Patrick is joined by Andy Singleton, Program Lead of the Global Parkinson’s Genetics Program (GP2), and Sonya Dumanis, COO of the Coalition for Aligning Science. They discuss the creation of GP2, how the initiative is closing representation gaps in genetics, and building global infrastructure and capacity for research.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Sonya and Andy
01:50 Aims and overview of the Global Parkinson’s Genetics Program (GP2)
03:15 The Aligning Science Across Parkinson’s (ASAP) initiative and how it led to the creation of GP2
04:37 Gaps in Parkinson’s genetics that inspired the creation of GP2
07:21 Closing the global representation gap in Parkinson’s genetics
08:37 ASAP’s model for long-term resources and adaptive funding
11:18 How GP2 overcame pandemic disruptions and data-sharing challenges to grow global capacity
15:01 Using harmonized data to compare Parkinson’s with other neurological diseases
17:02 Expanding GP2’s scope while keeping Parkinson’s at the core
18:42 Using genetics to guide targeted Parkinson’s therapeutics
21:37 Early biomarkers beyond genetics including proteomics and alpha-synuclein seed amplification assay (SAA) to guide therapy timing
23:01 Adapting GP2 to incorporate new discoveries and build capacity for functional and longitudinal studies
26:54 Insights from GBA variants into gene expression and Parkinson’s risk biology
28:24 How GP2’s open access data can be used to power clinical trials and advance drug development
31:37 Lessons from GP2 on building sustainable global collaboration and capacity that can be applied across disease areas
36:10 Navigating global differences in genetic testing access, regulation, and return of results across the GP2 network
38:29 Building coalitions between philanthropy, nonprofits, and industry to sustain large-scale initiatives
41:09 The story behind the GP2 tattoos and the team spirit that fuels the program
42:23 Closing remarks
Find out more
GP2 (https://gp2.org/)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Wanda Smith, founder of CureGRN. They discuss Wanda’s journey from caring for her mother to driving FTD research, the discovery of progranulin and development of new therapies, the diagnostic odyssey and need for earlier genetic testing, and how the CureGRN community is expanding support and awareness worldwide.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Wanda
02:18 Wanda’s journey into frontotemporal dementia (FTD) research from being a caregiver to establishing a brain bank
06:31 Shifting focus after the discovery of progranulin (GRN) and accelerating FTD research through collaboration
08:23 How GRN haploinsufficiency drives FTD and what it means for therapy
11:57 Implication of progranulin in neurodegenerative diseases and therapies now in clinical trials
13:33 Why earlier genetic testing and diagnosis are critical for families with GRN mutations
15:31 Barriers behind the diagnostic odyssey and limited access to genetic testing
17:03 Moving from symptom-based diagnosis to early diagnosis with biomarkers
19:50 Expanding CureGRN’s reach through global collaboration
21:14 Raising awareness to drive FTD research
22:44 Overcoming stigma and shame to encourage trial participation in FTD
24:41 Navigating family conversations about FTD with compassion and meeting people where they are
26:39 Providing multiple pathways for families to access support, education, and community
28:35 Insights into the future of FTD and addressing the gaps preventing progress in care and diagnosis
30:58 The importance of genetic testing and community resources in FTD
33:23 The role of younger gene carriers in shaping early detection, prevention, and long-term care in FTD
37:00 Closing remarks
Find out more
CureGRN (https://www.curegrn.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
This week on The Genetics Podcast, Patrick is joined by Terry Pirovolakis, CEO and Founder of Elpida Therapeutics. They discuss Terry’s journey to create a life-saving gene therapy for his son, the founding of Elpida Therapeutics to bring hope to families with ultra-rare diseases, and the challenges of scaling therapies that aren’t commercially viable.
Show Notes:
0:00 Intro to The Genetics Podcast
00:58 Welcome to Terry
01:24 The beginning of Terry’s gene therapy journey after his son Michael was diagnosed with SPG50
03:24 Learning the biotech industry and building a gene therapy team
05:17 Terry’s experience with learning about gene therapy without a scientific background
06:42 The process of building a gene therapy in under three years during the COVID-19 pandemic
09:30 Fundraising through community support and major donors
11:06 Expanding access of Michael’s gene therapy to children all over the world
12:32 The creation of Elpida Therapeutics to develop non-commercially viable therapies and adapting to a challenging funding landscape
15:24 Insight into cost, accessibility, and the role of endpoints and manufacturing
20:06 Learning from safety events as gene therapy scales and the importance of considering the risk/reward ratio in rare disease
23:24 Landscape of precision therapeutics available today beyond AAV vectors
27:09 Designing trials at Elpida to demonstrate efficacy in ultra-rare disease
29:24 Adapting meaningful endpoints to disease progression and FDA flexibility
34:02 Background of Priority Review Vouchers and the negative impact of its non-renewal on rare disease funding
37:48 Finding optimism in rare disease family initiatives and gene therapy successes, and the future of advanced therapeutics
41:07 How to support the rare disease community and families
44:16 Closing remarks
Find out more
Elpida Therapeutics (https://www.elpidatx.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
This week on The Genetics Podcast, Patrick is joined by Samuli Ripatti, Director of the Institute for Molecular Medicine Finland (FIMM), Vice Director at HiLIFE, and Professor of Biometry at the University of Helsinki. They discuss Samuli’s research on lipid and cardiovascular genetics, how polygenic risk scores are moving into clinical care, and the power of the FinnGen biobank.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Samuli
01:48 Samuli’s path from statistics to genetics at the beginning of a new era
03:09 Remembering Leena Peltonen and the Human Genetics Summer School
05:46 Samuli’s research in lipid and cardiovascular genetics and the power of collaboration
09:14 Integrating polygenic risk scores into cardiovascular and breast cancer care
14:52 Using medication history in FinnGen to uncover cardiometabolic genetics and predict treatment patterns
18:50 The future of polygenic risk scores in predicting prognosis and guiding treatment
21:21 The confounding effect of treatment in genetic studies
23:14 Overview of FinnGen and its impact on genetics and drug discovery
27:04 The next 5 years in proteomics and molecular profiling to move beyond associations
29:56 Using polygenic risk scores in clinical trials
31:41 Future directions, from refining phenotypes in large biobanks to piloting clinical applications of polygenic risk scores
34:04 Scaling population biobanks versus deep phenotyping and why the future requires both
35:29 Closing remarks
Find out more
Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases (https://www.nature.com/articles/s41591-022-02122-5)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Jonathan Marchini, Head of Statistical Genetics and Machine Learning at the Regeneron Genetics Center. They discuss Jonathan’s pioneering role in developing computational methods from the HapMap era through to today, how those innovations underpin large-scale imputation and analysis, and why exomes with imputation remain more powerful than whole genomes for discovery at Regeneron.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Jonathan
01:47 Jonathan’s career path from teaching in rural Tanzania to genomics research at Oxford
04:43 Lessons from the HapMap era and the birth of imputation
08:30 Ongoing challenges with data sharing and usable tools
10:30 Handling massive genetic datasets at Regeneron and developing new computational methods to scale
15:26 Key discoveries from the million-exome paper
18:04 Pushing computational limits in meta-analysis
19:50 Polygenic risk scores in the clinic and their role in trial design
23:38 Why Regeneron prioritizes exomes with imputation over whole genomes and what that means for discovery
27:58 Where AI truly adds value in genomics and where simpler models still win
32:27 Interpreting rare variants, the promise of protein models, and why better phenotyping is key
35:31 Closing remarks and opportunities at Regeneron
Find out more
Regeneron Genetics Center (https://www.regeneron.com/science/genetics-center)
Million exome paper (https://www.nature.com/articles/s41586-024-07556-0)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Max Bronstein, CEO of Aviva Strategies. They discuss the shifting regulatory and political landscape shaping biotech, the realities of today’s drug development process, and why new incentives and flexible trial pathways are critical to advancing rare and ultra-rare disease therapies.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Max
01:51 Regulatory shifts and FDA challenges under the new administration
05:40 Overview of the regulatory process for therapeutic development and the push for patient-centered trials
11:26 Challenges in drug development from regulatory gaps to shifting FDA priorities
15:45 Unprecedented government turnover and its impact on biotech industry stability
18:32 Status and significance of the pediatric priority review voucher program for rare and ultra-rare disease development
22:02 How Congress uses “must-pass bills” to advance or block health policies
25:17 Max’s role in creating Advanced Research Projects Agency for Health (ARPA-H) to drive high-risk innovation
30:02 How ARPA-H is funded
31:21 Adapting science policy to politics
33:35 Breakthroughs in rare disease therapies and the policy frameworks needed to ensure access
37:15 Lessons from the Orphan Drug Act and why new incentives are needed to make ultra-rare disease drug development viable
39:23 The push for flexible rare disease trial pathways and the disconnect between FDA rhetoric and practice
43:26 Closing remarks and a call to connect for patient organizations and rare disease parents
Find out more
Aviva Strategies (https://www.avivastrategies.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
This week on The Genetics Podcast, Patrick is joined by Richard Wilson, Senior Vice President, Primary Focus Lead of Genetic Regulation at Astellas. They discuss where the gene therapy field stands today, diving into successes, persistent barriers, regulatory considerations, manufacturing strategies, and other reflections on important approaches to precision medicine drug development.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Richard
01:33 Current wins and challenges in gene therapy
07:13 The need for more open non-competitive data sharing and a clearer pathway towards reimbursement and incentivization
11:15 Building post-approval systems into the genomic medicine lifecycle
14:47 Rethinking evidence standards in rare disease trials, and the global push for regulatory and reimbursement alignment
20:28 Genetic medicine breakthroughs in central nervous system diseases
22:25 The challenges of starting clinical development with an end in mind
24:34 The need for careful analysis around endpoints, vector design, and delivery approaches
29:33 Navigating regulatory hurdles when making mid-program changes to vectors or payloads
31:16 Strategies for enhancing scalability and quality of gene therapy manufacturing
36:05 Exploring other delivery methods beyond AAV
39:32 Getting ready for the Timmerman Traverse and raising nearly $1M for Life Science Cares
43:48 A call to refocus on patients, partnership, and purpose in uncertain times
45:55 Closing remarks
Find out more
Astellas (https://www.astellas.com/)
Timmerman Traverse fundraising for Life Science Cares (https://timmermantraverse.blackbaud-sites.com/)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, we celebrate our 200th episode with a look back at some of the earliest episodes, particularly ones that foresaw major trends or went on to spark real-world impact. These include Eric Topol’s early predictions about AI in healthcare, Laurence Reid’s vision for gene therapy in hearing loss, Sir Rory Collins on the potential impact of the UK Biobank, Daphne Koller on uniting biology and machine learning, and Vineeta Agarwala on harnessing large datasets for drug discovery. Patrick adds updates and reflections on how these bold ideas have shaped the genomics and biotech landscape.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Overview of episode content and guests featured
01:47 Eric Topol predicts the role of AI in healthcare in 2019
05:58 Patrick’s reflections on AI’s progress today and future potential
06:57 Laurence Reid outlines Decibel Therapeutics’ gene therapy plans for otoferlin-related hearing loss
10:58 Patrick’s updates on Decibel’s success and acquisition by Regeneron
11:44 Sir Rory Collins on the creation and vision of the UK Biobank
18:20 Patrick on the lasting impact of open science and the UK Biobank
19:10 Daphne Koller on building insitro to fuse biology and machine learning
24:30 Patrick on the future of large-language models in biology
25:55 Vineeta Agarwala on investing in large datasets for drug discovery
32:24 Patrick on applying multi-omic data to rare disease research
32:52 Closing remarks
Find out more
The Genetics Podcast is now on Instagram! Follow us for clips from recent episodes and release announcements (https://www.instagram.com/thegeneticspodcast/).
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
This week on The Genetics Podcast, Patrick is joined by Xin Jin, Associate Professor in the Department of Neuroscience at The Scripps Research Institute. They discuss how in vivo Perturb-seq enables scalable and high-resolution modeling of neurogenetic disorders like autism, how introducing mutations directly into living mouse brains reveals cell-type vulnerabilities and convergent pathways, and why this approach could transform therapeutic development by identifying shared mechanisms across diverse genetic mutations.
Show Notes:
0:00 Intro to The Genetics Podcast
00:58 Welcome to Xin
01:52 Overview of in vivo Perturb-seq
05:10 Identifying de novo variants in autism spectrum disorder
09:00 Using perturbations to map how autism-linked mutations affect specific brain cell types
13:04 Applying Perturb-seq to other brain diseases
14:30 In vivo versus in vitro models and extending genetic screening approaches beyond the brain
18:44 Using in vivo models to trace variant effects, rank gene drivers, and uncover therapeutic pathways
22:35 Conservation of genes between mouse and human in the context of neurodevelopmental disease modeling
24:21 Impact of genetic discoveries on drug development by convergence onto common pathways
27:22 Xin’s early interest in science through her grandfather’s work in plant taxonomy and botany
29:48 Xin’s path from China to MIT and how early research shaped her scientific mindset
31:58 Reflections on AI’s rapid progress and limits in biology, and the need for new models
37:21 Closing remarks
Find out more
Jin lab (https://www.jin.scripps.edu/)
In vivo Perturb-seq explainer video (https://vimeo.com/549737357)
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
This week on The Genetics Podcast, Patrick is joined by Benny Sorensen, CEO of Hemab Therapeutics. They discuss how Hemab is reimagining clotting therapies by centering patient voices, how persistence and being “unreasonable” led to their first program, and the value of their multi-modality and collaborative approach.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Benny
01:49 Reimagining blood clotting therapies by listening to lived experience and embracing the biotech revolution
04:27 How persistence and patient voices sparked Hemab’s first drug development program
07:13 Overview of Glanzmann Thrombasthenia (GT) and Hemab’s antibody-based approach
10:09 Evolution of hemophilia treatment and neglected blood clotting disorders
14:18 Genetic and gender considerations around bleeding disorders
17:41 Hemab’s range of therapeutic modalities and the value of collaboration
21:00 Why deep domain expertise drives Hemab’s strategy and success
22:55 Lessons from the drug development process
24:16 Global insights into gender bias, health inequality, and bleeding disorder care
26:46 Upcoming milestones at Hemab
29:52 Lessons from running natural history studies to capture the patient experience
33:25 Redefining the patient journey through data
34:40 How Benny’s experience at Alnylam Therapeutics shaped his “unreasonable” leadership
38:16 Reflections on being a father and a CEO
40:38 Closing remarks and Benny’s commitment to thoughtful drug development
Find out more
Hemab Therapeutics (https://www.hemab.com/)
Hemab trial register (https://shorturl.at/8AAQN)
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
Summary:
This week on The Genetics Podcast, Patrick is joined by Heiko Runz, medical geneticist and VP of Neuroscience at insitro. They discuss Heiko’s path into therapeutic genetics, how collaboration and data integration across biobanks led to his discovery of a protective variant for age-related macular degeneration, and the role of cell-based models in drug discovery.
Show Notes:
0:00 Intro to The Genetics Podcast
00:58 Welcome to Heiko
01:41 Heiko’s career path and how he became interested in medical genetics and therapeutic development
05:49 Connecting the dots across biobanks for genetic discovery
08:23 Heiko’s discovery of a potential gene target for age-related macular degeneration
15:29 The challenge of biobank recontact and why it’s essential for follow-up studies
18:57 The opportunity for smaller companies to follow up on large-scale genomic discoveries
23:00 Advances in cell-based models for neuroscience drug discovery
24:40 Heiko’s role in the development of tofersen for SOD1 ALS
28:50 Targeting TDP-43 in ALS through large-scale cell-based phenotyping and drug discovery
30:36 Using cell-based phenotypes to functionally test disease mechanisms and validate variants
33:58 The potential of AI for refining phenotypes and generating drug hypotheses
36:47 Heiko’s advice to early career professionals interested in the field of genetics and drug discovery
38:26 Closing remarks
Find out more
insitro (https://www.insitro.com), study on CFHR5 (https://www.nature.com/articles/s41467-025-61193-3)
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
This week on The Genetics Podcast, Patrick is joined by Molly He, CEO and co-founder of Element Biosciences. They discuss the current landscape of sequencing technologies, Element’s innovative sequencing platform, and the potential of using in-sample multiomic profiling across different stages of drug discovery.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Molly
01:42 Persistent barriers in precision medicine
04:54 Limitations of multiomics technologies and the unique advantage of Element’s approach
07:33 How Element started by inventing an ambitious sequencing instrument
11:33 Overview of the chemistry behind Element’s sequencing technology
14:41 Sequencing workflow of Element’s technology and technical advantages
18:24 Sequencing inside cells and drug discovery insights from a study on tyrosine kinase inhibitor (TKI) resistance pathways
25:57 Sequencing for CRISPR perturbation and direct genotype–phenotype linkage in the same cell
27:33 Whole-transcriptome in situ sequencing and applications in patient samples
29:19 Simplifying single-cell transcriptomics with direct in-sample sequencing
30:31 Applying the single-cell spatial technology to different steps of the drug discovery process
36:43 Competition in the sequencing industry and recent news about Illumina filing a patent infringement case against Element
38:43 Lessons from building Element over eight years
40:32 Insight into maintaining a cohesive culture as Element has multiplied in size and across countries
42:06 The importance of input data quality for AI applications and excitement about the possibility of predicting biology
45:40 Closing remarks
Find out more
Element Biosciences (https://www.elementbiosciences.com/)
Pre-print (https://www.biorxiv.org/content/10.1101/2025.05.06.652479v1)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
Summary:
This week on The Genetics Podcast, Patrick is joined by David Bumcrot, Chief Scientific Officer of CAMP4 Therapeutics. They discuss David’s involvement in the development of the breakthrough technologies in RNA interference and CRISPR, how CAMP4 is pioneering the use of regulatory RNAs to treat haploinsufficient diseases, and the complexities of gene regulation.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to David
01:57 David’s experiences at companies that developed RNA interference (RNAi) and CRISPR technologies
04:05 Lessons from translating RNAi to the bedside
05:58 The scalable chemistry of RNA versus the complexity of gene editing
07:48 Insight into the lack of rapid scalability and growth in gene therapy companies
09:19 How CAMP4 is using regulatory RNAs to boost gene expression in haploinsufficient diseases
13:01 Mapping and predicting the impact of specific regulatory RNAs on the expression of target genes
15:05 Why regulatory RNAs open up new target space without needing new drug modalities
16:27 How CAMP4 prioritizes certain diseases based on delivery feasibility and genetic evidence
18:31 Understanding expression thresholds in haploinsufficiency and building confidence in therapeutic targets
20:29 Comparing different approaches for increasing gene expression
22:39 Other therapeutic areas of focus for CAMP4, including urea cycle disorders and central nervous system (CNS) disorders
25:47 Lessons from early clinical development and engaging regulators on novel targets
27:47 Building high-resolution regulatory RNA maps beyond what public datasets can provide
31:04 Considerations around the treatment window for SYNGAP1
32:40 The value of collaborative frameworks for rapid therapy development
35:20 Rethinking early safety assessment and global regulatory strategies for RNA therapies
38:37 The importance of basic science, staying optimistic, and continuing to invest in biotech innovation
40:18 Closing remarks
Find out more
CAMP4 Therapeutics (https://www.camp4tx.com)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
Summary:
This week on The Genetics Podcast, Patrick is joined by Melissa Haendel, Director of Translational Informatics and Precision Health and Professor at the University of North Carolina at Chapel Hill, and Phenotypic Lead at Alamya Health. They discuss the limitations of electronic health records for rare disease diagnostics, how patient self-reporting can enhance diagnosis, expanding access to genomic testing in underserved settings, and the challenges and promise of national-scale health data infrastructure.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Melissa
02:05 Melissa’s career path, beginning with finding her first professorship on Craigslist
04:24 The fundamentals of ontology and how it can help identify common molecular mechanisms across different rare diseases
06:29 Why key rare disease details are missing from electronic health records (EHRs) and how ontologies and AI can help
11:33 How patient self-reporting using layperson phenotypic terms was associated with strong diagnostic performance
15:27 Why recognizing multi-system patterns is key for diagnosing rare conditions and how tools like pattern-based screening are improving outcomes
17:41 How Alamya Health is expanding access to genomic diagnostics by building local lab infrastructure in underserved communities
22:03 How Alamya’s single-test, AI-powered approach helps solve complex cases in underserved settings
24:18 Rethinking the true cost of delayed diagnosis, from wasted testing to the societal and family burden
26:10 What it takes to do national-scale health data research in the U.S. and a vision of real-world data as a public utility
33:37 Opening up access to national EHR data for research through health data networks
36:15 The gap between real-world data and clinical research and why improving data quality benefits both care and science
38:34 A major upcoming milestone in bringing unified rare disease codes into US healthcare with the Mondo ontology
41:22 Closing remarks
Find out more
TIS Lab (https://tislab.org/), Alamya Health (https://www.alamyahealth.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
Summary:
This week on The Genetics Podcast, Patrick is joined by Frank Gentile, Chief Executive Officer of Casma Therapeutics. They discuss the role of autophagy in neurodegenerative diseases, Casma’s work on therapies for Gaucher’s disease and Parkinson’s disease, and the challenges and opportunities in rare disease biotech.
Show Notes:
0:00 Intro to The Genetics Podcast
00:58 Welcome to Frank
02:00 Origin story for Casma Therapeutics and its therapeutic focus on autophagy
04:51 Diseases in which autophagy is dysregulated
07:46 The link between GBA1 and Parkinson’s, and why so many neurodegenerative diseases exhibit autophagy defects
12:28 Findings from Casma Therapeutics’ preclinical studies and associated mechanisms
16:46 Milestones and design of Casma Therapeutics’ upcoming clinical studies
20:24 Well-characterized cohorts of GDPD patients from natural history studies
21:55 Identifying alternative therapeutic targets involved in autophagy initiation that are mTOR independent
24:46 The negative effects of broad inhibition of mTOR
25:57 Advantages and disadvantages of using small molecule therapy versus broader gene therapy
26:59 Frank’s experience in investment and his approach to risk
29:15 Frank’s perspective on the current biotech climate and how investors view rare disease
32:16 Extending lead candidate and portfolio strategy to other therapeutic applications
34:15 Partnering opportunities and future potential of the TRPML1 program across neurodegenerative diseases
35:50 A potential link between autophagy pathways and longevity
37:20 Closing remarks
Find out more
Casma Therapeutics (https://www.casmatx.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