Precision BioSciences (DTIL) investor relations material

Clinical program updates

• PBGENE-HBV, a first-in-class gene editing therapy targeting cccDNA and integrated HBV DNA, showed dose-dependent, durable antiviral activity and a favorable safety profile in the Eliminate B phase I trial, with no dose-limiting toxicities observed across 22 administrations in nine patients.

• The highest dose cohort (0.8 mg/kg) demonstrated the greatest and most sustained HBsAg declines, with all patients approaching levels that may allow for stopping nucleoside analogs and testing for cure.

• First-ever clinical biopsy data confirmed on-target gene editing in the liver, with up to 28% indel formation after two doses and further S antigen reduction after a third dose, correlating with HBsAg decline.

• The study enrolled a diverse, real-world population and is expanding globally, with plans for a part two dose expansion, up to 45 participants, and regulatory clearance for new sites.

• PBGENE-DMD, targeting Duchenne muscular dystrophy, is on track for IND filing by year-end and clinical trial initiation in early 2026, leveraging preclinical data showing significant muscle function gains and long-term durability.

Safety and mechanistic insights

• PBGENE-HBV was well tolerated across all dose levels, with transient, manageable infusion reactions, ALT/AST elevations, and no evidence of Hy's law, cumulative toxicity, or liver dysfunction.

• No dose-limiting toxicities were observed; adverse events were predictable, transient, and resolved without intervention.

• Extensive preclinical and clinical assessments showed no detectable off-target editing or genomic instability at therapeutic doses.

• The mechanism targets cccDNA and integrated HBV DNA, aiming for functional or complete cure by eliminating or inactivating viral reservoirs.

• Biopsy and serum data correlated gene editing with S antigen decline, supporting proof of mechanism.

Efficacy and antiviral activity

• All patients across three dose cohorts showed antiviral activity, with durable HBsAg reductions observed, especially at higher doses.

• Dose-dependent effects were established, with the highest dose cohort (0.8 mg/kg) showing the greatest rate of HBsAg decline and deepening responses.

• Durable HBsAg reductions were sustained over time, with up to 66% reduction in Cohort 2 and 64% in Cohort 3.

• Biopsy data confirmed PBGENE-HBV's mechanism of action, with molecular evidence of viral DNA editing and elimination.

• Activity was independent of baseline viral load, with patients having long histories of HBV and NUC treatment.