Rocket Pharmaceuticals, Inc. announces positive clinical updates from its Phase 1 Danon Disease Trial for RP-A501 through an oral poster session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2022. This includes updated safetyand efficacy data from patients in the pediatric and adult cohorts which demonstrate that RP-A501 was generally well tolerated and conferred clinical benefit. The following assays were performed, validated and reported for patients with at least six months of follow-up.

Vacuolar area: In the first pediatric patient (1008), vacuolar area as assessed by an automated method in representative biopsy samples was found to have decreased by 77% at six months. Six-month biopsy results are not yet available for the second pediatric patient (1009). All adult patients have also seen meaningful decreases in vacuolar area ranging from 26% to 74% at most recent available timepoints.

Brain natriuretic peptide (BNP): In the pediatric cohort, BNP, a key marker of heart failure, decreased from a pretreatment baseline by 78% in patient 1008 at nine months and by 62% in patient 1009 at six months. All patients in the pediatric and adult cohorts showed stabilization or meaningful decreases in BNP, with the most dramatic increases observed in patients with higher baseline BNP (90% for patient 1002 in the adult cohort at 30 months and 78% for patient 1008 in the pediatric cohort at nine months). Adult patients demonstrated reduction in BNP of greater than 75% from mean pretreatment baseline compared to mean values at 18 to 24 month timepoints.

Troponin: The pediatric patients, despite a more limited six and nine months of follow-up, were observed to have meaningful decreases in high sensitivity troponin I (hsTnI), a protein in the blood showing signs of cardiac injury, of 90% and 85%, respectively. Patients in the adult cohorts demonstrated significant decreases in hsTnI. Notably, the four adult patients were observed to have a reduction in troponin of greater than 75% from mean pretreatment baseline to mean values at 18 to 24 months that was sustained in the three adult patients who are currently 30 to 36 months post-treatment.

New York Heart Association (NYHA) Class: In the pediatric cohort, an improvement (from Class II to I) in NYHA class, a measure of the symptoms and functional limitations resulting from heart failure, was observed in both patients. In the adult cohorts, all three patients treated with a closely monitored immunomodulatory regimen showed improvement in NYHA class (from II to I). Stabilization of NYHA class was observed in one adult patient treated at the low dose without a closely monitored regimen.

Kansas City Cardiomyopathy Questionnaire (KCCQ): Patients in the pediatric cohort showed significant improvement in KCCQ Overall Score, a measure (0-100) of physical and social limitations, symptoms and quality of life in patients with heart failure. Specifically, patient 1008 demonstrated improvement from a pretreatment baseline of 50 to 93 at nine months and patient 1009 demonstrated improvement from a pretreatment baseline of 52 to 81 at three months. All patients treated in pediatric and adult cohorts with a closely monitored immunomodulatory regimen showed improvements ranging between three and 43 points when comparing baseline to the most recent available timepoint.

Left ventricular (LV) wall thickness: In the pediatric cohort, patient 1008 demonstrated reduction in maximum LV wall thickness by 3% from treatment baseline after six months of follow-up. In the adult cohort, all four patients demonstrated a reduction of greater than 15% and greater than 20% from mean baseline in both LV posterior wall thickness in diastole and maximum LV wall thickness, respectively, compared to mean values at 18 to 24 months, which represents improvement of the ventricular hypertrophy. RP-A501 was observed to be generally well tolerated at the low dose with a manageable safety profile across pediatric and adult cohorts.

In the pediatric cohort, RP-A501 was well tolerated in both patients with six to eleven months follow-up. The patients were observed to have normal-range platelets, minimal complement activation and no complement-related adverse events. The two patients received a modified immunomodulatory regimen to mitigate adverse events.

No significant immediate or delayed toxicities, significant skeletal myopathy, or late transaminase elevations have been observed to date. Taken together, these results are consistent with a positive benefit/risk profile for RP-A501 in Danon Disease. Phase 1 enrollment and treatment are complete.

RP-A501 together with the enhanced immunomodulatory regimen appears well tolerated and effective in the pediatric cohort. In the adult cohort, RP-A501 stabilizes and potentially improves Danon Disease cardiomyopathy. Early pediatric data are encouraging and consistent with improvements at similar or earlier timepoints compared to the adult cohorts.

Findings are supportive of Phase 2 evaluation of RP-A501 in Danon Disease. RP-A501 is an investigational gene therapy product being developed for Danon Disease and the first potential gene therapy for monogenic heart failure. It consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a functional version of the human LAMP2B transgene (AAV9.LAMP2B).

RP-A501 is currently being evaluated in a Phase 1 clinical trial; preliminary data from this study's low-dose cohort showed that RP-A501 was generally well tolerated and conferred evidence of improved cardiac function.