Generation Bio (GBIO) Canaccord Genuity 44th Annual Growth Conference & Private Company Showcase 2024 summary

Strategic platform overview

• Focus on developing redosable, durable genetic medicines for rare and prevalent diseases using two mutually reinforcing platforms: a ligand-targeted lipid nanoparticle (ctLNP) delivery system and immune-quiet DNA cargo.

• ctLNP enables selective, efficient in vivo delivery to previously inaccessible cell types, notably T cells and hematopoietic stem cells (HSCs).

• Immune-quiet DNA technology avoids innate immune sensors, supporting long-lasting gene expression.

• Portfolio targets three main areas: T cell delivery for autoimmune diseases, HSC delivery for sickle cell and related disorders, and hemophilia A.

• Strong cash position with $217 million, funding operations through the second half of 2027.

ctLNP delivery system advancements

• Achieves efficient, dose-dependent transduction of T cells at low doses, with minimal off-target delivery to liver and spleen.

• Stealth LNP design extends half-life in circulation to over 8 hours in non-human primates, compared to 8-10 minutes for traditional LNPs.

• Delivers less than 1% of dose to liver and spleen, enabling low dosing and high potency.

• No new safety concerns observed with extended LNP half-life; components have established clinical safety.

• Highly tunable targeting ligands (VHH nanobodies) allow for precise targeting of cell subtypes and optimization of receptor engagement.

T cell and HSC program progress

• In vivo T cell programming enables redosable CAR T therapies, potentially expanding access and applications beyond oncology to autoimmune and infectious diseases.

• Demonstrated 10% transduction of circulating and splenic T cells at 0.5 mg/kg, with CAR expression levels matching those correlated with clinical efficacy.

• Partnership with Moderna focuses on redosable CAR T for autoimmunity using mRNA cargo, while DNA applications remain in-house except for a limited number of programs.

• HSC targeting leverages similar delivery strategies, with flexibility to optimize for diseased or healthy marrow environments.

• Multiple gene editing systems under evaluation for sickle cell, with a focus on upregulating fetal hemoglobin (HbF) and progressing through preclinical milestones into next year.