Pharmacology-Toxicology

Pharmacology and Toxicology preclinical animal studies are crucial to the development of efficacious and safe new medicines. We support your needs from early-stage candidate screening using research-grade AAV vectors to GLP dose finding and toxicology studies with QA oversight using GMP-comparable AAV vectors. Additional services include histology and image analysis supporting the evaluation of vector tropism and transgene expression as well as GLP-compliant histopathology primary and secondary evaluations by ACVP-certified pathologists.

Franklin Biolabs performs GLP-compliant studies in house and does not rely on third-party laboratories to ensure end-to-end quality control and to save time and costs. Our experienced study directors engage with clients to design and execute studies tailored to each project’s specific needs. We are able to conduct pharmacology studies for AAV and LNP mRNA modalities to evaluate efficacy, pharmacodynamics, and pharmacokinetics in genetic disease models. Our team has technical and scientific expertise in highly specialized routes of administration specific to genetic medicine (e.g., intra-ocular, cerebrospinal fluid, direct brain parenchymal, etc.) as well as the ability to perform investigative pathology to elucidate mechanism(s) of action in the case of unexpected toxicity. The experience and expertise at Franklin Biolabs go beyond traditional CROs to support the development of your genetic medicine and deliver IND-ready reports.

For more information on the impact of animals in advancing rare disease research, please click here.

Study Services

Research pharmacology study services (early discovery through clinical candidate declaration)

Screen test article candidates, either provided by the client (various genetic medicines) or made by Franklin Biolabs (research-grade AAV)

-Transgene expression with/without target engagement, RNA interference and gene knock-down in vitro
-Pharmacodynamics/efficacy and Pharmacokinetics/biodistribution in rodents and NHP models
-NHP pilot studies to confirm scalability and establish preliminary safety profile ahead of formal GLP toxicology assessment (early de-risking of preclinical assets)
-Mechanism of action assessment and investigative pathology consulting services available in case of unexpected toxicity profile

GLP-compliant IND-enabling study services (following clinical candidate declaration)

Lead candidate(s) test-article either provided by the client (various genetic medicines) or made by Franklin Biolabs (GMP-comparable grade AAV)

-Dose-finding pharmacology studies to determine minimal effective dose in mouse model of disease and evaluate BLA-enabling surrogate biomarkers. GLP-compliance level dependent on the incorporation of safety readouts
-Formal GLP toxicology/safety study in healthy NHPs including biodistribution/excretion

Pathology Services

Franklin Biolabs provides an end-to-end, in-house histology technical platform for all research and GLP histology needs.

Pathology services include:
-Necropsy (full or partial); retinal dissection; brain mold; gross pathology report
-Tissue processing, paraffin and cryo embedding
-Sectioning, H&E and special stains as needed
-Histopathology analysis and report by ACVP-certified pathologist

Evaluation of vector tropism and transgene expression in the cellular and tissular context via multiplex in situ hybridization (e.g., for transgene RNA, vector DNA). Special staining is also available for reporter gene detection (e.g., GFP, LacZ), enzyme activity (e.g., OTC, GUSB), immunofluorescence, and immunohistochemistry (IHC)

Scanning services include fluorescence and brightfield microscopy, slide scanning, and image analysis for a fully digital workflow. We use an ISH/IHC autostainer for improved reproducibility and higher throughput.

Additional services include project-specific image analysis/transgene expression quantification through development of applications within Visiopharm tailored to the client’s needs (note that slides can be provided to the client directly).