Generation Bio (GBIO) Jefferies Global Healthcare Conference 2025 summary

Strategic vision and platform innovation

• Developing a first-in-class siRNA delivery system targeting T cells for autoimmune diseases, aiming for a first IND in the second half of 2026.

• The platform uses a cell-targeted lipid nanoparticle (LNP) system with a biological ligand for highly selective T cell delivery, avoiding off-target effects in the liver and spleen.

• Achieves efficient, ligand-dependent uptake in T cells, with 95%-100% delivery to target T cells in preclinical models.

• The system enables knockdown of intracellular targets in both naive and activated T cells, with durable effects and potential for reversible intervention.

• Plans to announce lead targets and indications in August, with milestones leading to the first IND in late 2027.

Disease focus and differentiation

• Targeting high-value autoimmune indications with significant unmet need, such as alopecia, vitiligo, ulcerative colitis, Crohn's disease, primary biliary cholangitis (PBC), and type 1 diabetes.

• Aims to provide disease-modifying therapies where none exist, especially in PBC and type 1 diabetes.

• Seeks to improve response rates and durability in diseases like ulcerative colitis, where current therapies have a 30% response ceiling.

• The approach may allow selective reduction of effector T cell function while preserving regulatory T cells, potentially enabling durable disease control.

• Targets are broadly expressed in CD4, CD8, and NK cells, with initial focus on T cell-driven pathologies.

Competitive landscape and technical challenges

• No other companies have succeeded in delivering siRNA to T cells with conjugate mechanisms due to delivery barriers.

• Antibody-based approaches are limited to extracellular targets and risk unwanted T cell activation.

• Small molecules lack selectivity, affecting multiple cell types and causing off-target effects.

• The LNP system's ability to deliver siRNA intracellularly to T cells is a key differentiator and competitive advantage.

• Ongoing business development activities in the RNAi space are seen as positive validation for the field.