Prime Medicine (PRME) investor relations material

Key program milestones and clinical development

• Two in vivo programs for Wilson's disease and alpha-1 antitrypsin deficiency are set to enter the clinic, with clinical data expected in 2027.

• The ex vivo program for chronic granulomatous disease is being revived due to regulatory flexibility and patient need, with a potential BLA submission as early as this year or next.

• Regulatory filings for Wilson's disease are planned for the first half of this year, and for alpha-1 antitrypsin deficiency by mid-2026.

• Cash runway guidance remains unaffected by these developments.

Strategic and regulatory considerations

• FDA has shown increased flexibility for high unmet need indications, reducing both cost and complexity for approval.

• CMC requirements and associated costs for the CGD program have dropped significantly, making the investment more attractive.

• The company is considering enrolling one more pediatric patient to potentially broaden the label for CGD.

• Plans are in place to pursue global regulatory strategies, especially for mutations prevalent in different populations.

Clinical trial design and endpoints

• Wilson's disease phase 1 will be a dose escalation study, measuring endpoints like copper metabolism normalization, urinary copper, liver biopsy, and ceruloplasmin levels.

• Early proof of concept may be demonstrated by radiolabeled copper PET studies and reduction in standard of care dependency.

• For alpha-1 antitrypsin deficiency, clinical development will leverage established biomarkers and frameworks, focusing on AAT levels.