Executive Summary

Developing gene therapies for rare monogenic disorders requires preclinical models that accurately forecast human physiological responses. Non-human primate (NHP) models offer the highest translational fidelity for evaluating the in vivo safety and tolerability of novel AAV-based constructs, particularly for disorders affecting the central nervous system. A robust NHP modeling strategy involves precise model sourcing, comprehensive veterinary characterization, and rigorous in-life management and observation. This approach de-risks clinical development and supports an accelerated path to regulatory submission, typically within an 18-24 month IND timeline.

The Challenge of Modeling Monogenic Disease in a Translational Species

For gene therapies targeting rare genetic disorders, selecting an appropriate animal model is a pivotal decision that influences the entire development program. While rodent models are useful for initial research, their predictive value for human safety is limited. The significant neuroanatomical and immunological differences between rodents and humans can lead to a misinterpretation of a vector’s potential safety and tolerability profile.

Non-human primate models bridge this translational gap. Their genetic proximity and physiological complexity provide a more accurate system for assessing how a therapeutic vector will be tolerated in a clinical setting. This is particularly true for evaluating delivery to the CNS, observing for potential immune-mediated adverse events, and understanding the long-term safety profile of a gene therapy candidate.

Our Approach to NHP Model Development and In-Life Care

A successful NHP study begins with a deep understanding of the target disease’s pathophysiology. Our approach involves a collaborative process to align the in-life study design with the goals of the development program.

• Phenotypic Sourcing and Maintenance: We identify and source animals with key disease-relevant phenotypes, ensuring the colony provides a stable and appropriate biological context for the planned in vivo study.

• Dose Route and Administration: We leverage advanced surgical and imaging capabilities to support clinically relevant routes of administration. This precision ensures the preclinical study design accurately reflects the intended human trial protocol.

The strategic insights derived from studies evaluating AAV gene therapies in large animal models (PMID: 35333110) underscore the value of this approach. Demonstrating a favorable safety profile in a highly translational species provides a strong foundation for advancing a candidate toward clinical investigation.

Animal Welfare and Enhanced Responsibility

All animal studies at Franklin Biolabs are conducted with an unwavering commitment to ethical and humane treatment. Our programs, which leverage a >100,000 sq ft facility, operate in strict compliance with USDA regulations and follow the standards of AAALAC International. We are dedicated to the principles of the 3Rs (Replacement, Reduction, and Refinement) as a core component of our scientific and ethical framework.