Frequently Asked Questions (FAQ)

Executive Summary

Evaluating the long-term safety and efficacy of AAV-based ocular gene therapies requires specialized, longitudinal study designs that extend well beyond acute-phase analysis. Successful programs depend on demonstrating durable transgene expression and a stable, long-term safety profile, particularly concerning immunogenicity and systemic exposure. Our pharmacology studies are designed to generate the comprehensive, IND-enabling data package necessary to de-risk clinical transition, leveraging deep expertise in ocular biology and AAV vectorology to support an 18-24 month IND timeline.

Sustained Expression and Durable Efficacy

A primary objective for ocular gene therapy is achieving stable, long-term expression of the therapeutic transgene. The durability of this expression directly correlates with the potential for a lasting clinical benefit. As demonstrated in long-term studies, AAV vectors are capable of mediating sustained protein production for years, establishing the principle of a durable effect (PMID: 15507527).

Our study designs focus on characterizing this durability through:

• Functional Assays: Utilizing relevant in vivo models to measure sustained therapeutic activity over the full study duration.

• Molecular Analysis: Quantifying transgene expression levels in target ocular tissues at multiple time points.

• Pharmacodynamic Readouts: Correlating expression levels with relevant biomarkers to establish a clear dose-response and duration-of-effect relationship.

“We started collaborating with UPenn Vector core in 2023 and the AAV vector which they manufactured laid a foundation for development of a gene therapy candidate which will enter soon preclinical studies. The key people from UPenn Vector Core joined Franklin Biolabs and our partnership transitioned without interruption from UPenn Vecor Core to Franklin Biolabs Research Vector Division. Franklin Biolabs is our trusted partner in our AAV-vector based gene therapy candidate development and we hope to continue the partnership for years to come.”
— Biotech Partner

Comprehensive Safety Pharmacology for IND Submission

A robust safety assessment is a core component of any IND application. For ocular AAV therapies, this involves a multi-faceted evaluation of both local and systemic safety. The goal is to build a comprehensive safety profile that satisfies regulatory requirements, drawing from principles established in studies that successfully balanced significant therapeutic benefit with favorable safety outcomes (PMID: 35333110).

Our GxP-compliant safety studies, conducted in our >100,000 sq ft facility, provide a complete picture of the test article’s safety profile. This approach has contributed to a 100% IND success rate for programs conducted since 2019. (The Franklin Biolabs brand itself launched in 2024, continuing a legacy of scientific excellence). We provide high-resolution pharmacology validating complex biologicals through rigorous evaluation of:

• Ocular Toxicity: In-life ophthalmic exams and terminal histology to detect any signs of inflammation, cellular damage, or structural changes.

• Systemic Exposure: Analysis of non-target tissue biodistribution to understand vector clearance and potential systemic effects.

• Immunogenicity: Assessment of both humoral and cellular immune responses to the AAV capsid and the transgene product.