Generation Bio (GBIO) TD Cowen Genetic Medicines & RNA Summit summary

Platform innovation and technology

• Developed cell-targeted lipid nanoparticle (ctLNP) delivery system, enabling selective delivery to tissues beyond liver and spleen, such as T cells and HSCs.

• ctLNP platform is adaptable, allowing delivery of various cargos including siRNA, mRNA, guide RNA, and immune-quiet DNA (iqDNA).

• Engineered iqDNA to be non-immunogenic and durable, supporting years-long expression from an episomal, non-integrating DNA cargo, and is being advanced to a second generation with increased potency.

• Rapid Enzymatic Synthesis (RES) enables high-purity, scalable, and cost-effective non-viral DNA manufacturing, supporting ongoing R&D and SAR optimization.

• Proprietary ligand and linker technologies enable modular, selective targeting for a range of cell types, supporting a broad pipeline of future indications.

Pipeline and program focus

• Portfolio targets autoimmune diseases, sickle cell disease, and hemophilia A, focusing on redosable in vivo CAR-T, in vivo editing, and individualized coverage to expand patient access and displace ex vivo and traditional approaches.

• T cell program enables re-dosable, point-of-care CAR-T therapies with flexible cargo and adjustable duration.

• HSC program aims to replicate validated ex vivo indel editing for sickle cell and beta thalassemia in an in vivo setting, expanding patient access.

• Hemophilia A program targets years-long endogenous Factor VIII expression, with individualized dosing and expanded access, aiming for longer duration and broader coverage.

• Cash runway extends to the second half of 2027, supporting advancement of clinical programs and expansion into new indications such as lysosomal storage diseases and inborn errors of metabolism.

Recent data and scientific advances

• At ASGCT, presented data showing ctLNPs deliver less than 1% of dose to liver/spleen, with 99% in systemic circulation and extended half-life in primates.

• Demonstrated efficient, selective in vivo T cell transduction, including functional CAR delivery and tumor-killing activity, with robust in vitro and in vivo data showing dose-dependent uptake and minimal off-target effects.

• HSC-targeting ctLNPs are 3-4 months behind T cell programs, with ongoing ligand optimization for selective delivery.

• In liver, exploring scFv and VHH ligands for more specific and potent targeting compared to GalNAc.

• Second-generation iqDNA scaffolds are being tested for Factor VIII, aiming for 50% expression at 0.5 mg/kg in mice.