Every Moment Matters: Developing an N-of-1 ASO for a Child with an Ultra-Rare Disease

Every Moment Matters: Developing an N-of-1 ASO for a Child with an Ultra-Rare Disease

Advances in sequencing, the emergence of antisense oligonucleotide therapies, and the advent of induced pluripotent stem cell technology are among the combination of factors that have made bespoke medicines for individual patients scientifically feasible. In the case of ultra-rare, genetic diseases, a child may face a progressive, life-threatening condition with no available treatments. As we continue our series on discovery with Charles River Laboratories, we take a look at how the organization partnered with global collaborators and a patient’s family to design, screen, and advance a highly selective antisense oligonucleotide therapy targeting a pathogenic allele underlying a child’s ultra-rare epileptic encephalopathy. We spoke to Charles River Lab’s Associate Research Leader Blanca Torroba and Group Leader of Neuropharmacology Johanna Uhari Väänänen about how they moved from concept to a candidate for a custom ASO therapy, steps they took to accelerate the process, and the challenges of advancing N of 1 medicines to an IND.nbRb

Every Moment Matters: A Case for Adaptive Immunogenicity Testing

Immunogenicity testing helps establish the safety of experimental therapies by ensuring drugs don’t trigger a potentially dangerous immune response. While regulators had long relied on a fixed, three-tier immunogenicity testing model, the industry is now shifting to a flexible, risk-based approach that continues to meet regulatory requirements and ensure patient safety. We spoke to Katie Sime, principal research scientist at Charles River Laboratories, about when reduced-tier approaches make sense, what regulators want to see; and why adaptive strategies can particularly benefit resource-constrained biotechs by balancing scientific rigor, patient safety, and budget constraints.

Every Moment Matters: The Power of Study Director–Advisor Partnerships

At Charles River Laboratories, scientific advisors and study directors have complementary roles in nonclinical drug development. Scientific advisors bring years of scientific and regulatory experience to program-level strategy, while study directors act as operational captains who execute individual studies under good laboratory practice. Close collaboration between the two plays a critical role in helping clients build coherent, IND-enabling safety packages. We spoke to Pramila Singh, senior principal scientific advisor at Charles River Laboratories, about how scientific advisor–study director collaborations are crucial for creating robust, regulatory-ready study designs, how they help prevent costly errors, and how they can accelerate development timelines.

Every Moment Matters: Getting Better Insights on Target and off Target Biology

Biologic drug development increasingly relies on sensitive, human relevant platforms capable of detecting both intended and unintended target engagement well before first in human studies. Charles River Laboratories is leveraging its Retrogenix cell microarray platform alongside traditional tissue cross-reactivity studies to gain a more comprehensive view of target and off-target biology. We spoke with Charles River Labs Associate Director of Advanced Modalities Mark Aspinall O’Dea and Charles River Labs Senior Scientific Director James Raymond, about how combining these two approaches helps sponsors select better leads, design safer studies, and meet regulatory expectations for complex modalities.

Every Moment Matters: How Integrated Teams De-Risk the Path from Discovery to IND

The journey from discovery to IND is rarely linear. It demands rigorous target validation, continuous regulatory engagement, and the use of translationally relevant models to effectively de risk programs before they advance. In this installment of Big4Bio’s ongoing series with Charles River Laboratories, we look at how the company’s One Step approach guides sponsors from discovery concept to IND-ready clinical candidate. We spoke to Manu Kohli, principal scientific advisor for Charles River Labs, about how the company’s integrated development model works, the benefits of having an end-to-end drug development solution under one roof, and how this approach helps deliver submission-ready assets on time and on budget.