Precision BioSciences (DTIL) Status Update summary

Program updates and strategic focus

• PBGENE-DMD, a gene editing therapy for Duchenne muscular dystrophy (DMD), is now a wholly owned lead program, with preclinical data showing durable functional muscle improvement and correction of the dystrophin gene in disease models.

• The approach targets the 45-55 exon hotspot, enabling production of a near full-length, functional dystrophin protein, with evidence of improved muscle force and protein expression sustained up to nine months in mice.

• ARCUS nucleases allow for efficient, precise editing at lower AAV doses, reducing safety risks and enabling single-vector delivery.

• IND-enabling work for PBGENE-DMD will be completed in 2025, with clinical trial initiation targeted for 2026; regulatory interactions with the FDA have aligned on analytical and trial design paths.

• The PBGENE-3243 mitochondrial program is paused for fiscal reasons, with plans to resume after progress in HBV and DMD programs.

Preclinical and clinical insights

• Preclinical studies show PBGENE-DMD treatment leads to significant, durable increases in muscle force and dystrophin protein expression, exceeding therapeutic thresholds observed in human Becker patients.

• Editing of satellite stem cells is demonstrated, supporting long-term durability and muscle regeneration.

• Lower AAV doses are effective, minimizing safety concerns and differentiating from microdystrophin therapies that require persistent high-dose AAV.

• The resulting dystrophin protein is functionally validated in humans, with literature supporting as little as 5% expression for clinical benefit.

• Safety is prioritized through high-quality AAV manufacturing and collaboration with experienced clinical teams.

Market and regulatory landscape

• DMD remains a high unmet need with 300,000-400,000 global patients and limited durable treatment options; PBGENE-DMD aims to address this gap.

• Regulatory strategy emphasizes linking biomarkers to functional improvement, aligning with evolving FDA perspectives on accelerated approval.

• Commercial strategy will initially focus on newly diagnosed patients, with antibody screening to address prior AAV exposure.

• Ongoing updates are planned for the HBV program, DMD clinical progress, and the iECURE OTC partnership.

• Cash runway extends into the second half of 2026, supporting planned clinical milestones.