Season 1 Episode Guide
Episode 1: Navigating the Complexities of Drug Discovery
Episode 2: How NAMs are Rewriting the Rules of Antibody Discovery
Episode 3: Transforming Discovery with Organoids
Episode 4: Integrating AI into Drug Discovery
Episode 5: DMPK’s Role in Making Better Drugs and Better Decisions
Episode 6: How Integrated Teams De-Risk the Path from Discovery to IND
Episode 7: Getting Better Insights on Target and off Target Biology
Episode 8: The Power of Study Director-Advisor Partnerships
Episode 9: A Case for Adaptive Immunogenicity Testing
Episode 10: Developing and N-of-1 ASO for a Child with an Ultra-Rare Disease
Episode 10
Every Moment Matters: Developing an N-of-1 ASO for a Child with an Ultra-Rare Disease
Guest experts: Blanca Torroba | Associate Research Leader and Johanna Uhari-Väänänen | Group Leader Neuropharmacology
In this episode, Blanca Torroba and Johanna Uhari-Väänänen from Charles River Laboratories take a dep dive into how their teams helped develop a fully personalized antisense oligonucleotide (ASO) therapy for a child with an ultra-rare epileptic encephalopathy caused by a KCNQ3 mutation. They explain how N of 1 therapies, especially ASOs, offer a uniquely rapid and precise way to target a patient’s exact genetic mutation, with advantages such as reversible dosing, higher safety margins, and flexible regulatory pathways that allow accelerated development. The child’s case exemplified this potential: a heterozygous mutation that disrupted the KV7.3 potassium channel provided a clear mechanistic rationale for an allele selective ASO designed to silence only the mutant gene while preserving normal function.
The episode details the massive multi-institution effort required to design and test a therapy for a single patient, including iPSC derived neurons, electrophysiology assays, and a screening pipeline that narrowed approximately 500 ASOs to a top candidate showing strong selectivity, efficacy, and CNS distribution. Sites across the US and Europe collaborated in parallel to assess potency, immunotoxicity, tolerability, and biodistribution, critical for a disease where time is essential. As the program approaches IND submission, the conversation highlights the power of even small clinical improvements for families and reflects on the future of personalized ASO therapies, noting that while the science is advancing rapidly, funding and ecosystem alignment remain major barriers to widespread adoption.
Episode 9
Every Moment Matters: A Case for Adaptive Immunogenicity Testing
Guest expert: Katie Sime | Principal Research Scientist
In this episode, Katie Sime, Principal Research Scientist at Charles River Laboratories, reflects on how conversations around immunogenicity testing are evolving as the field reexamines the long standing multi-tier paradigm used in clinical programs. She considers how advancing science and improved assay technologies are enabling more flexible, adaptive strategies. Sime revisits the origins of the traditional screening, confirmatory, and titer tiers, processes shaped by conservative regulatory expectations to protect patient safety and acknowledges both their strengths and their constraints. As therapeutic modalities diversify and risk profiles vary, scientists are increasingly asking when these tiers are essential and when they may create unnecessary complexity or resource demands.
Using a case study from Zealand Pharma, she describes how teams are evaluating streamlined approaches such as replacing a titer tier with signal to noise assessments and retaining the confirmatory tier only when specificity is a concern. These examples are not positioned as universal solutions but illustrate how data-driven, risk-based reasoning can support alternative options. Sime emphasizes that adaptive immunogenicity strategies, grounded in robust assay performance, rigorous validation, and early insight into ADA trends, may offer meaningful future value. She highlights the importance of early regulatory dialogue, thoughtful assay design, and transparent justification when proposing a shift from traditional models, reflecting a field collaboratively exploring ways to improve efficiency and align testing with modern drug development.
Episode 8
Every Moment Matters: The Power of Study Director-Advisor Partnerships
Guest expert: Pramila Singh | Senior Principal Scientific Advisor
In this episode, Pramila Singh, Senior Principal Scientific Advisor at Charles River Laboratories, explains how scientific advisors and study directors work together to strengthen nonclinical drug development. She describes the advisor as a strategic partner who brings deep regulatory and scientific experience to shape program level planning, ensuring study designs are scientifically sound, aligned with regulatory expectations, and positioned to avoid costly missteps. The study director importantly oversees day to day study conduct, GLP compliance, and data interpretation, making the partnership powerful because their roles are distinct yet complementary.
Dr. Singh emphasizes that early, collaborative communication between scientific advisors and study directors enables stronger protocols, clearer biomarker strategies, better species and model selection, and more resilient study designs that can accommodate evolving regulatory expectations, including the increased use of New Approach Methodologies (NAMs). She shares real examples where this collaboration corrected design gaps, resolved unexpected issues, and aligned broader elements like CMC, pharmacology, and clinical plans to create cohesive IND enabling packages. For lean or virtual biotechs notably, the advisor–study director team effectively extends internal capabilities, supporting confident decisions, fewer repeat studies, and more efficient paths to the clinic.
Episode 7
Every Moment Matters: Getting Better Insights on Target and off Target Biology
Guest experts: Mark Aspinall O'Dea | Associate Director and Jim Raymond | Senior Scientific Director
Mark Aspinall O’Dea and Jim Raymond from Charles River Laboratories discuss how the Retrogenix® cell microarray platform enhances early discovery decisions and strengthens preclinical safety assessment. They explain how the technology, featuring a cell-based microarray expressing more than 6,500 human extracellular and membrane proteins, enables precise mapping of on and off-target binding for biologics, small molecules, ADCs, and advanced modalities like cell and gene therapies. This capability helps researchers uncover subtle or modality-specific off-target interactions that traditional tissue-based assays often miss.
Our experts describe how Retrogenix® integrates with tissue cross reactivity (TCR) studies, noting strong internal concordance data and emphasizing the value of using the assays together to identify safety liabilities earlier, reduce rework, and accelerate IND-enabling progress. They share real-world examples where Retrogenix® insights allowed teams to redesign molecules, reprioritize leads, or avoid late-stage toxicology failures, especially in complex modalities like engineered antibodies, ADCs, and AAV vectors. They also highlight emerging expansions into neuroscience libraries, organoid models, and AI-driven prediction, all aimed at improving early safety assessment and reducing late-stage attrition.
Episode 6
Every Moment Matters: How Integrated Teams De-Risk the Path from Discovery to IND
Guest experts: Manu Kohli | Principal Scientific Advisor
Dr. Manu Kohli, Principal Scientific Advisor at Charles River Laboratories, brings a rare, sponsor-centric perspective shaped by decades of experience, deep scientific rigor, and firsthand understanding of the real-world challenges biopharma teams face. His approach reflects a commitment to helping clients make confident, informed world challenges biopharma teams face. His approach reflects a commitment to helping clients make confident, informed decisions early that ultimately determine downstream success.
Dr. Kohli explains how strong translational strategy, relevant biological models, and integrated workflows like Charles River’s One Step program expedite development by unifying pharmacology, DMPK, CMC, safety, regulatory strategy, and project management. This coordinated approach reduces redundancy, improves communication, and helps teams anticipate problems before they threaten timelines. He concludes by advising sponsors to validate targets thoroughly, begin regulatory planning early, integrate CMC and toxicology considerations from the start, and work with experienced partners who can seamlessly align scientific and operational components for a smoother path to IND.
Episode 5
Every Moment Matters: DMPK’s Role in Making Better Drugs and Better Decisions
Guest experts: Mike Templin | Senior Director Scientific Advisory Services
Michael V. Templin, PhD, DABT, Senior Director of Scientific Advisory Services at Charles River Laboratories, discusses the pivotal role of DMPK in the overall pathway of determining whether a compound can become a safe, effective, and commercially viable drug. He explains how DMPK integrates core ADME considerations and evolves throughout nonclinical drug discovery and development – from evaluating metabolism, stability, and absorption in early research, to refining exposure profiles, dose selection, and therapeutic index estimates in later stages.
Dr. Templin highlights how continuous DMPK assessment helps de-risk programs, guides toxicology and clinical strategy, and shapes business decisions such as competitive positioning and go/no-go evaluations. He also looks ahead to emerging tools, noting that AI-driven modeling, in silico prediction, and organoid-based systems will play an increasingly important role in improving predictive accuracy with large and complex data sets. Nevertheless, human insight and judgement remain essential in decision-making for high-consequence outcomes that require a deep understanding of the dynamics involved in biologic processes.
Episode 4
Every Moment Matters: Integrating AI into Drug Discovery
Guest experts: Alison Jones | Senior Science Director and Laura Lotfi | Director, Digital Product Management
In this episode of the Big4Bio Podcast, host Daniel Levine speaks with Alison Jones, Senior Science Director, and Laura Lotfi, Director of Digital Product Management at Charles River Laboratories, about how artificial intelligence (AI) and machine learning are revolutionizing drug discovery.
The discussion highlights the Logica® AI platform, which combines computational power with experimental science to accelerate timelines, reduce attrition, and improve candidate quality. They also explore virtual control groups (VCGs) as a breakthrough in reducing animal use while maintaining scientific rigor. Key topics include the role of data diversity, closed-loop discovery systems, and risk-sharing business models in driving innovation. The episode highlights the enduring importance of human scientific judgment alongside AI, envisioning a future of personalized medicine, accelerated development, and ethical research practices.
Episode 3
Every Moment Matters: Transforming Discovery with Organoids
Guest experts: Ludo Buti | Senior Research Leader and David Fischer | Chief Technology Officer, Discovery and Safety Services
In this episode of the Big4Bio Podcast, we explore the transformative role of complex cell models, including organoids and multi-cell cultures in drug discovery and safety testing. Featuring Ludo Buti, Senior Research Leader, and David Fischer, Chief Technology Officer for Discovery and Safety Services at Charles River Laboratories, the discussion explores how advanced cell models integrate into New Approach Methodologies (NAMs) and their potential to reduce animal testing, enhance predictive modeling, and expedite early-stage drug development.
Episode 2
Every Moment Matters: How NAMs are Rewriting the Rules of Antibody Discovery
Guest experts: Sarah Gould | Director, Senior Principal Scientific Advisor and Omar Aziz | Scientific Business Director
In this episode of the Big4Bio Podcast, host Daniel Levine speaks with Sarah Gould, Director, Senior Principal Scientific Advisor, and Omar Aziz, Scientific Business Director at Charles River, about the transformative role of New Approach Methodologies (NAMs) in antibody discovery and development.
The discussion explores how NAMs can accelerate drug development by improving predictive toxicology, reducing reliance on animal testing, and enhancing human relevance in safety and efficacy assessments. The conversation also covers the strategic integration of NAMs into discovery pipelines, the evolving regulatory landscape, and the future of monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates. Dr. Gould and Dr. Aziz emphasize collaboration, technological innovation, and regulatory alignment as key drivers for advancing safer, faster therapeutic programs.
Episode 1
Every Moment Matters: Navigating the Complexities of Drug Discovery
Guest experts: Justin Bryans | Chief Scientific Officer (Early Discovery) and Steve Bulera | CVP and Chief Scientific Officer (Safety Assessment)
At Charles River, we understand that drug discovery is a complex and high-risk endeavor, one that demands scientific excellence, cutting-edge technologies, and a strategic mindset to overcome challenges and accelerate progress. Every moment matters in the discovery process, and our teams are deeply committed to helping our partners identify and advance promising therapeutic candidates with agility and precision.
We’re proud to collaborate with Big4Bio, hosted by Daniel Levine, on a new series spotlighting our drug discovery and development services. Over the past five years, Charles River has played a role in more than 80% of the novel drugs approved by the FDA, a testament to the impact of our integrated approach and deep scientific expertise.
In this inaugural episode, our Chief Scientific Officer of Early Discovery, Dr. Justin Bryans, and our Vice President and Chief Scientific Officer for Discovery and Safety Assessments, Dr. Steve Bulera, share insights into the evolving landscape of drug discovery. They discuss the challenges researchers face, the importance of timing, and how our collaborative model empowers innovation and drives success for our partners.
This podcast series was made in collaboration with Big4Bio and presented by Daniel Levine of Levine Media Group.