Rocket Pharmaceuticals (RCKT) Study update summary

Program updates and clinical progress

• Three cardiovascular gene therapy programs are in the clinic: Danon disease, PKP2 arrhythmogenic cardiomyopathy, and BAG3 dilated cardiomyopathy, all progressing rapidly.

• FDA has cleared the path to dose the remaining nine patients in the Danon pivotal trial after a previous safety hold; the trial remains a 12-patient single-arm study, with the first three patients treated under the modified protocol counting toward the pivotal population.

• The recalibrated dose for Danon is 3.8 × 10¹³ vector genomes/kg, based on safety, efficacy, and analytical characterization, aligning with prior phase I dosing and supported by nonclinical bridging data.

• The immunosuppressive regimen was modified after safety events, now using extended rituximab cycles and PRN eculizumab, with no recent TMA or capillary leak observed in the first three patients.

• Patient identification for Danon is robust, with more than nine eligible patients identified and a global recruitment strategy in place.

Study design, endpoints, and regulatory interactions

• Danon pivotal trial uses co-primary endpoints: myocardial LAMP2 protein expression and ≥10% reduction in LV mass index at 12 months, as agreed with the FDA.

• The trial is a responder analysis; not all patients must meet endpoints for a positive outcome.

• FDA interactions have been collaborative and favorable, with guidance for rare disease gene therapy becoming increasingly supportive.

• These endpoints are intended to support a potential accelerated approval pathway.

• A comprehensive Danon and portfolio update is scheduled for October 6, 2026, covering epidemiology, safety, and program status.

Safety and protocol modifications

• No clinical or laboratory evidence of thrombotic microangiopathy or capillary leak syndrome observed in the first three patients under the modified protocol.

• The modified protocol includes a recalibrated dose, optimized immunomodulatory regimen, enhanced eligibility criteria, safety monitoring, and risk-mitigation measures.

• Safety events such as TMA and capillary leak occur early (within 1-2 weeks), while transaminitis may appear later but has been manageable.

• The immunosuppressive regimen now uses extended rituximab cycles and PRN eculizumab.

• Initial clinical experience at the recalibrated dose and supportive product-bridging data reinforce the path forward.