Generation Bio (GBIO) 2024 Cantor Fitzgerald Global Healthcare Conference summary

Advances in in vivo genetic medicine

• In vivo reprogramming of T cells and HSCs is progressing, aiming for redosable, point-of-care therapies that expand patient access and avoid the need for ablation required in ex vivo approaches.

• Delivery to hepatocytes using iqDNA enables long-term gain of function, with hemophilia A as a lead indication and potential expansion to lysosomal storage disorders and other genetic diseases.

• The goal for hemophilia A is to achieve factor VIII replacement levels that prevent bleeding, with aspirations for multi-year freedom from disease and global accessibility.

Innovations in LNP delivery technology

• LNPs have been re-engineered to avoid serum opsonization, resulting in less than 1% liver and 0.1% spleen targeting, and extending half-life in circulation to over 8 hours in non-human primates.

• Small format antibodies are used to direct LNPs to specific cell types, opening new possibilities for selective delivery to T cells and HSCs.

• Preclinical studies show effective transduction of T cells at low doses, with good tolerability and no significant immune activation in animal models.

• LNPs are rapidly taken up by target cells, are biodegradable, and their selectivity allows for potent genetic medicine delivery.

Preclinical and collaborative development

• LNPs are being evaluated in humanized mice and non-human primates, with upcoming data releases to inform further development.

• Collaboration with Moderna focuses on T cell delivery, with each party advancing separate programs based on cargo type, and potential for future joint programs.

• The delivery system is expected to enable new applications in T cell immunomodulation, including autoimmune and autoinflammatory diseases.