BioTalk Unzipped

Long-acting Cell-Based Gene Therapy, Fabry Disease and Beyond with Glafabra CEO, Dr. Chris Hopkins

In this episode of BioTalk Unzipped, hosts Gregory Austin and Dr. Chad Briscoe sit down with Glafabra CEO: Dr. Chris Hopkins, geneticist, biochemist, and biotech entrepreneur, to explore the science and strategy behind next generation cell-based gene therapies for rare diseases. With more than 25 years of experience spanning gene augmentation, rare disease biology, CRISPR licensing, and biotech formation, Dr. Hopkins shares how autologous, ex vivo engineered cell therapies may overcome key limitations of current enzyme replacement and viral gene therapies, particularly for Fabry disease. The conversation dives deep into: • How lentiviral gene augmentation in patient derived cells enables sustained enzyme production • Why redosing matters and where one time AAV therapies fall short • The scientific rationale for early intervention, including potential newborn treatment • Differences between autologous and emerging allogeneic approaches • Regulatory pathways for rare disease therapies and recent FDA developments • The role of non animal models in translational research • Montana’s early access therapy law and its broader implications • Building biotech platforms amid a challenging funding environment Topics include cell based gene therapy, Fabry disease, lentiviral vectors, stem cell engineering, rare disease drug development, regulatory science, and translational medicine. Subscribe to BioTalk Unzipped for in depth conversations with the scientists and leaders shaping the future of biomedical innovation. 00:00 - Intro 00:53 – Welcome to BioTalk Unzipped, Guest intro: Dr. Chris Hopkins 02:10 – Guest charity: Environmental Defense Fund 03:12 – His journey into rare-disease therapeutics and Glafabra 05:58 – Discovering a new enzyme-deficiency therapy 06:39 – Current standard of care 07:42 – How the new autologous cell therapy works 09:40 – Treating patients earlier (even newborns) 10:33 – Emerging therapies - AAV gene therapy vs. cell-based therapy 12:16 – Long-term results & repeat dosing 14:30 – Future plans: T-cells & allogeneic approaches 18:08 – New News: FDA resubmission for rare disease 20:00 – Navigating FDA pathways 22:06 – Non-animal testing & alternative models 25:50 – Montana’s early-access therapy law & medical tourism 29:03 – Could other states follow? 31:31 – Biotech’s current funding challenges 33:46 – New News: Gene therapy trial saves 4-year-old 37:09 – Long-term vision for expanding therapies 39:53 – Personal segment: outdoor life & skiing 44:43 – Guest question on international trade Dr. Christopher Hopkins https://www.linkedin.com/in/christopherehopkins/ [https://www.linkedin.com/in/christopherehopkins/] Glafabra - https://www.glafabra.com/ [https://www.glafabra.com/] Environmental Defense Fund - https://www.edf.org/ [https://www.edf.org/] Dr. Chad Briscoe https://www.linkedin.com/in/chadbriscoe/ [https://www.linkedin.com/in/chadbriscoe/] Celerion - https://www.celerion.com/ [https://www.celerion.com/] Gregory Austin https://www.linkedin.com/in/gregoryaustin1/ [https://www.linkedin.com/in/gregoryaustin1/] Celerion - https://www.celerion.com/ [https://www.celerion.com/] New News Articles: US FDA asks Stealth BioTherapeutics to resubmit application for rare genetic condition therapy https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-asks-stealth-biotherapeutics-resubmit-application-rare-genetic-condition-2025-05-29/ [https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-asks-stealth-biotherapeutics-resubmit-application-rare-genetic-condition-2025-05-29/] Gene therapy trial saves boy, 4, from 'death sentence' https://www.thetimes.com/uk/healthcare/article/gene-therapy-trial-great-ormond-street-70l2sgqw [https://www.thetimes.com/uk/healthcare/article/gene-therapy-trial-great-ormond-street-70l2sgqwj] Montana, revolutionary law passed: unlimited research for longevity https://en.ilsole24ore.com/art/montana-approved-revolutionary-law-researching-longevity-without-limits-AHmDI7BB?refresh_ce=1 [https://en.ilsole24ore.com/art/montana-approved-revolutionary-law-researching-longevity-without-limits-AHmDI7BB?refresh_ce=1] KEY TAKEAWAYS 1. A NEW CELL THERAPY COULD REPLACE LIFELONG ENZYME TREATMENTS FOR FABRY PATIENTS. 2. UNLIKE GENE THERAPY, THIS TREATMENT CAN BE REDOSED — NO ONE-AND-DONE LIMIT. 3. EARLY INTERVENTION, EVEN IN NEWBORNS, MAY BECOME POSSIBLE. 4. MONTANA’S NEW LAW COULD OPEN A FAST LANE FOR EXPERIMENTAL THERAPIES IN THE U.S. 5. DESPITE A TOUGH FUNDING CLIMATE, BREAKTHROUGHS SHOW GENE-EDITED CELL THERAPIES ARE RESHAPING THE FUTURE. #CELLTHERAPY #GENEEDITING #RAREDISEASE #BIOTECHINNOVATION #GENETICMEDICINE #HEALTHCAREFUTURE #MEDICALBREAKTHROUGH #CellBasedGeneTherapy #RareDisease #FabryDisease #GeneAugmentation #LentiviralVectors #Biotech #TranslationalScience #GeneticMedicine #BioTalkUnzipped https://youtu.be/VcPXZmK-XU8 [https://youtu.be/VcPXZmK-XU8]

Fail Fast, Learn Faster: Drug Development in Rare Disease with Dr. Binodh DeSilva

In this episode of BioTalk Unzipped, Gregory Austin and Dr. Chad Briscoe sit down with Dr. Binodh DeSilva, Senior Vice President of Bioanalysis at Ultragenyx Pharmaceutical, to explore the science and soul behind rare-disease drug development. From her early days studying electrochemistry at the University of Kansas to leading cutting-edge bioanalytical programs at Ultragenyx, Dr. DeSilva shares how curiosity and community shaped her four-decade career. She discusses the profound responsibility of working with limited, often irreplaceable patient samples with care. A special thanks to AAPS (https://www.aaps.org/ [https://www.aaps.org/]) for their help and support of this episode. The conversation dives into: * Balancing rigor and agility in small-population clinical studies * Leveraging entrepreneurial mindsets from biotech within big pharma frameworks * The promise of dried blood spots (DBS) and patient-centric sampling * Mentorship, curiosity, and the future of scientific leadership * Her return to Sri Lanka with KU faculty to recruit the next generation of scientists Throughout the discussion, DeSilva underscores a recurring theme: science thrives when curiosity meets compassion. This episode is a masterclass in both. Guest Links Dr. Binodh DeSilva https://www.linkedin.com/in/binodh-desilva/ [https://www.linkedin.com/in/binodh-desilva/] Ultragenyx Pharmaceuticals - https://www.ultragenyx.com/ [https://www.ultragenyx.com/]  Hosts Dr. Chad Briscoe https://www.linkedin.com/in/chadbriscoe/ [https://www.linkedin.com/in/chadbriscoe/]  Celerion - https://www.celerion.com/ [https://www.celerion.com/]   Gregory Austin https://www.linkedin.com/in/gregoryaustin1/ [https://www.linkedin.com/in/gregoryaustin1/]  Celerion - https://www.celerion.com/ [https://www.celerion.com/]   Keywords: BioTalk Unzipped, Binodh DeSilva, Ultragenyx, rare disease research, bioanalysis, dynamic drug development, dried blood spots, DBS sampling, biologics, AAPS NBC 2025, Gregory Austin, Chad Briscoe, Celerion, scientific leadership, mentorship in science, biopharma innovation, curiosity in research, Sri Lanka scientists, analytical chemistry, pharma innovation, drug development ethics.

Unlocking Antibody Development with AI with Dr. Pin-Kuang Lai

In this episode of BioTalk Unzipped, hosts Gregory Austin and Dr. Chad Briscoe interview Asst. Professor Pin-Kuang Lai from Stevens Institute of Technology about his keynote speech at AAPS NBC 2025 and the intersection of AI and molecular engineering, particularly in predicting the viscosity of monoclonal antibodies. They discuss the challenges of high concentration formulations, the importance of AI validation, and the future of formulation development. Lai shares insights from his international research journey and collaborations with pharmaceutical companies, as well as opportunities for students interested in this field. 00:00 Preview & Intro 01:58 Deep Viscosity and AI in Antibody Development 04:39 AI Validation and Model Reliability 07:12 International Journey and Collaborative Research 08:42 Future of Formulation Development 10:30 AAPS NBC Experience 11:30 Academic vs. Industry Career Paths 12:31 Collaboration with Pharmaceutical Companies 13:59 Modeling Protein Aggregation Challenges 14:43 Student Engagement and Research Opportunities 15:45 Expanding Applications of Machine Learning Dr. Pin-Kuang Lai https://www.linkedin.com/in/pin-kuang-lai/ Stevens Institute of Technology - https://www.stevens.edu/ Dr. Lai’s Publications - https://www.linkedin.com/in/pin-kuang-lai/details/publications/ The DeepViscosity Model - https://devpred.onrender.com/DeepViscosity Dr. Chad Briscoe https://www.linkedin.com/in/chadbriscoe/ Celerion - https://www.celerion.com/ Gregory Austin https://www.linkedin.com/in/gregoryaustin1/ Celerion - https://www.celerion.com/

The Science and Hope of Brain Cancer with Dr. Robert Thorne, Denali Therapeutics

In this powerful episode (#35) of BioTalk Unzipped, recorded live at the AAPS NBC conference in Boston, Gregory Austin engages in a deep conversation with a leading Neuroscientist, Dr. Robert Thorne, Denali Fellow at Denali Therapeutics, for an intimate and scientific deep dive into the evolving world of brain cancer treatment and CNS drug delivery. Both Gregory and Dr. Thorne share personal stories of losing family members to brain metastases, weaving in the emotional 'why' behind their professional paths. Dr. Thorne highlights the complexities of the blood-brain barrier, the heterogeneity of brain metastases, and cutting-edge delivery technologies—including focused ultrasound and molecular engineering approaches. The conversation also touches on pediatric brain tumors like diffuse midline glioma (DIPG), emerging research in lysosomal storage diseases, and the collaborative spirit driving innovation in neuroscience today. This is more than a technical discussion—it’s a human story about grief, hope, and the relentless pursuit of better outcomes for patients with brain diseases. 00:00 Preview & Intro 01:10 Robert Thorne’s Reflections on the AAPS NBC conference 03:14 The Professional Biotech and Pharma League 05:09 A Personal Story Shared: Family Loss to Brain Cancer 07:57 My Reason for Optimism Treating Brain Cancer 08:50 Why Brain Metastases Remain Hard to Treat 11:10 Scientific Advances in Drug Delivery for Brain Cancer 12:30 Seed and Soil Concept in Oncology 15:18 Pediatric Brain Tumors: DNET, DIPG, and Beyond 16:49 Looking Ahead: Hope for Future Therapies 21:32 Closing Gratitude Dr. Robert Thorne https://www.linkedin.com/in/robert-g-thorne/ [https://www.linkedin.com/in/robert-g-thorne/] Denali Therapeutics - https://www.denalitherapeutics.com/ [https://www.denalitherapeutics.com/]  Dr. Chad Briscoe https://www.linkedin.com/in/chadbriscoe/ [https://www.linkedin.com/in/chadbriscoe/]  Celerion - https://www.celerion.com/ [https://www.celerion.com/]   Gregory Austin https://www.linkedin.com/in/gregoryaustin1/ [https://www.linkedin.com/in/gregoryaustin1/]  Celerion - https://www.celerion.com/ [https://www.celerion.com/]   KEY TAKEAWAYS: * Personal Connection Fuels Professional Passion: Both Gregory and Dr. Thorne were driven into the life sciences field by family experiences with brain tumors. * The Blood-Brain Barrier (BBB) Remains a Major Challenge: Brain metastases from cancers like melanoma, lung, and breast cancer still present difficult delivery barriers for therapies. * Heterogeneity in Brain Mets: Different metastases within the same patient can have vastly different BBB permeability, requiring multifaceted delivery strategies. * Emerging Drug Delivery Innovations: Focused ultrasound, engineered biologics, and Denali’s own delivery platforms are all promising ways to improve CNS drug penetration. * Pediatric Brain Cancers Present a Unique Set of Challenges: Diseases like diffuse midline glioma (DIPG) remain largely untreatable, but learnings from lysosomal storage disorders may translate in the future. * The Power of Community in Science: The conference setting highlights how collaboration and diverse perspectives drive breakthroughs in bioanalysis and drug development.

Inside AAPS NBC with AAPS President Dr. Russ Weiner

In this special episode (#34) of BioTalk Unzipped, recorded live at the AAPS NBC conference in Boston, Gregory Austin and Dr. Chad Briscoe sit down with AAPS President Dr. Russ Weiner for an unfiltered look inside AAPS NBC, at the state of rare disease research, the evolution of therapeutic modalities, and the human stories that drive scientific innovation. From navigating the emotional weight of personal loss to watching his son experience the field firsthand, Russ shares not only his scientific insights but the heart behind his leadership. The conversation spans topics like the rising promise of AI diagnostics, challenges with biomarker sampling logistics, the role of CROs in rare disease trials, and the future of autologous vs. allogeneic therapies. Dr. Weiner also offers an inspiring vision of industry collaboration, sharing how organizations like AAPS are becoming conduits for progress across low- and middle-income countries, underrepresented diseases, and emerging biotechnologies. Whether you're in the lab, the boardroom, or on the frontlines of clinical trials, this episode will reignite your sense of purpose in this field. 00:00 Preview & Intro 01:22 What is conference life like as AAPS President 02:27 Mentoring & Fatherhood at AAPS 03:54 Setting up the Meeting Season for AAPS 05:43 Life back in the Rare Disease Space - a Passion 10:58 The different costs of pharmaceutical & biotech research 12:59 The generosity of Rare Disease Patients 14:41 Dr. Chad Briscoe asks Russ what can we do to help advance Rare Disease efforts 19:57 Rare Disease conversations happening at AAPS and global reach 22:37 Broad use of new technologies, including Olink 24:10 Biggest change expected in Pharma in 10 years Dr. Russ Weiner https://www.linkedin.com/in/russellweiner/ [https://www.linkedin.com/in/russellweiner/]  AAPS - https://www.aaps.org/home [https://www.aaps.org/home]  Dr. Chad Briscoe https://www.linkedin.com/in/chadbriscoe/ [https://www.linkedin.com/in/chadbriscoe/]  Celerion - https://www.celerion.com/ [https://www.celerion.com/]   Gregory Austin https://www.linkedin.com/in/gregoryaustin1/ [https://www.linkedin.com/in/gregoryaustin1/]  Celerion - https://www.celerion.com/ [https://www.celerion.com/]   Takeaways: * Treating rare diseases early is not only life-saving—it’s economically sound. Gene and cell therapies may carry high price tags, but they dramatically reduce long-term costs. * The diagnostic delay for rare diseases—often 4 to 7 years—remains one of the biggest barriers to treatment. AI-powered diagnostics and data integration could change that. * Dr. Russ Weiner shares how personal loss fueled his career in science and how mentoring the next generation, including his son, brings it full circle. * The shift toward allogeneic cell therapies and in vivo CAR-T treatments will be key to driving down costs and increasing global accessibility. * CROs must evolve: future-ready organizations will localize biomarker analysis and forge relationships with rare disease investigators to improve site performance. * Technologies like Olink are revolutionizing biomarker discovery, enabling cost-effective, high-resolution multiplexing that was previously out of reach. * Spatial imaging, AI pathology, and facial-recognition-based diagnosis are the next wave of precision medicine. Quotes “Treating rare disease isn’t just compassionate—it’s a smart investment. Do the math, and curing someone can be far cheaper than managing chronic care for a lifetime.” “You can’t say it’s not in your backyard when that backyard becomes yours the moment you're on the same plane.” (on global health and infectious disease risk) “Some of the most generous people in clinical research are rare disease patients. They fight so no one else has to.” “It took me six months to even scratch the surface of this portfolio—rare disease isn’t just rare, it’s overwhelmingly complex.”