Rocket Pharmaceuticals (RCKT) Study Update summary

Study design and patient population

• Phase I trial of RP-A501 gene therapy in male patients with Danon disease, a rare X-linked disorder causing severe cardiomyopathy and neuromuscular deficits.

• Three dosing cohorts: low-dose adults/adolescents, high-dose adults/adolescents, and low-dose pediatric patients.

• Exclusion of patients with neutralizing antibodies to AAV9; all received immunomodulatory regimens.

• Baseline: all patients had severe LV hypertrophy, elevated cardiac biomarkers, and NYHA Class II symptoms.

• All six evaluable patients were alive and transplant-free up to age 25 years.

Safety and tolerability

• RP-A501 was generally well tolerated; most adverse events were mild or moderate and not related to the therapy.

• All serious adverse events (SAEs) occurred within 2-4 months post-dosing and were reversible.

• Treatment-related SAEs included transient AST/ALT elevation, pyrexia, and nausea/vomiting in low-dose adults.

• High-dose patient experienced complement-mediated TMA and acute kidney injury, fully recovered.

• No treatment-related SAEs in the pediatric cohort at the selected low dose.

Efficacy and biomarker outcomes

• Durable LAMP2 protein expression observed in all evaluable patients at 12 months and sustained up to five years in one patient.

• All patients showed stable LVEF and sustained reductions in LV mass index (median ~24% reduction), with all meeting ≥10% reduction at 12 months.

• Substantial reductions in BNP (~57%) and cardiac troponin (~84%) were observed 24-54 months after treatment.

• All patients improved from NYHA Class II to Class I and reported significant quality of life gains (mean KCCQ score +26 points).

• Morphologic improvements included reduced vacuoles in cardiomyocytes and evidence of tissue remodeling.