Slide 1: Investor Deck: Preliminary Data from Phase 1 Trial of RP-A601
NVESTOR DE I CK INVESTOR DECK INVESTOR DECK Preliminary Data from Phase 1 Trial of RP-A601 May 2025 ©2025 Rocket Pharmaceuticals, Ltd. All rights reserved
Slide 2: Forward Looking Statement and Disclosures
FORWARD LOOKING STATEMENT AND DISCLOSURES Various statements in this presentation concerning Rocket’s future expectations, plans and prospects that involve risks and uncertainties, as well as assumptions that, if they do not materialize or prove incorrect, could cause our results to differ materiall
Slide 3: PKP2-ACM (Plakophilin 2-Arrhythmogenic Cardiomyopathy)
3 PKP2-ACM (Plakophilin 2-Arrhythmogenic Cardiomyopathy) Mean age at presentation: 35 ± 18 years1 Estimated prevalence: 50,000 (US+EU)3-5† †Utilizing the conservative ACM prevalence of 1 in 5000 and the aggregated mean of 32.9% PKP2 mutation frequency in ACM calculated based on 2,572 ACM patients as
Slide 4: ACM: High-Risk of Arrhythmias and Sudden Cardiac Death
4 ACM: High-Risk of Arrhythmias and Sudden Cardiac Death No Currently Available Curative Treatment Options ACM, arrhythmogenic cardiomyopathy; ARVC, arrhythmogenic right ventricular cardiomyopathy; ARVD, arrhythmogenic right ventricular dysplasia; ICD, implantable cardioverter defibrillator; SCD, su
Slide 5: AAV Gene Therapy for PKP2-ACM: RP-A601
5 AAV Gene Therapy for PKP2-ACM: RP-A601 hGH, human growth hormone; ISO, isoproterenol; KO, conditional knock-out; PVC, premature ventricular contractions; WPRE, woodchuck hepatitis virus post-transcriptional regulatory element. 1. Herzog CD, et al. Preclinical Efficacy and Safety of AAVrh.74-PKP2a
Slide 6: Phase 1 Study Overview
6 Phase 1 Study Overview First-in-Human, Phase I, Open-label, Dose Escalation Trial of RP-A601 in Adult Patients with PKP2-ACM Clinicaltrials.gov Identifier: NCT05885412. ACM, arrhythmogenic cardiomyopathy; GC, genome copies; ICD, implantable cardioverter-defibrillator; IV, intravenous; SAE, serious
Slide 7: Baseline Characteristics of Cohort Patients
7 Baseline Characteristics of Cohort 1 Patients *Indicates patient still receiving specified agent as of baseline screening visit. †As assessed on Day -14 pre-infusion. Patient ID Sex Age at Enrollment (y) Weight at Dosing (kg) History of Anti-Arrhythmic Agents KCCQ-12 Score NYHA Class† RV Systolic
Slide 8: Most Frequently Reported Treatment Emergent Adverse Events Were Mild or Moderate
8 Most Frequently Reported Treatment Emergent Adverse Events Were Mild or Moderate in Severity* No dose-limiting toxicities observed – patients received a single intravenous RP-A601 dose: 8x1013 GC/kg † Pancreatitis, bacteremia, and sepsis were part of a single SAE Serious adverse events were coded
Slide 9: RP-A601 VCN and PKP2 RNA Expression in Endomyocardial Biopsy Tissue
9 *Month 12 data for Patient 1003, and Month 6 data for Patients 1011 and 1010. RP-A601 VCN and PKP2 RNA Expression in Endomyocardial Biopsy Tissue RP-A601 Vector Copy Number (DNA Copies Per Diploid Nucleus) Patient ID Baseline Most Recent Visit* 1003 0 2.89 1011 0 3.81 1010 0 8.23 PKP2 Exogenous mR
Slide 10: RP-A601 Increased PKP2 Protein Expression at 3 and 6 Months
10 RP-A601 Increased PKP2 Protein Expression at 3 and 6 Months Cardiac biopsies (n=2 of 3) show increased PKP2 protein expression following RP-A601 treatment ~2.1X (110%) change from baseline to 6 months in Patient 1011 ~5X (398%) change from baseline to 6 months in Patient 1010 Patient 1003 shows i
Slide 11: RP-A601 Increases Expression of Desmosomal Proteins & Cadherin-2 in Patient 1003
11 Data cutoff April 2025. RP-A601 Increases Expression of Desmosomal Proteins & Cadherin-2 at 6 and 12 Months in Patient 1003 baseline 3 months 6 months 12 months 12 11 10 9 8 7 6 5 4 3 2 1 0 CDH2 positive cardiac tissue (%) baseline 3 months 6 months 12 months 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 n
Slide 12: Immunofluorescence Shows Increased PKP2 & Cadherin-2 Expression in Patient 1003
12 Data cutoff April 2025. Immunofluorescence Shows RP-A601 Increased PKP2 & Cadherin-2 Expression at 6 and 12 Months in Patient 1003 RP-A601 promotes PKP2 and Cadherin-2 expression at 6 and 12 months RP-A601 promotes increased co-distribution of PKP2 and Cadherin-2 at cell-cell junctions at 6 and 1
Slide 13: RP-A601 Increases Desmosomal Proteins & Cadherin-2 in Patient 1011
13 Data cutoff April 2025. RP-A601 Increases Expression of Desmosomal Proteins & Cadherin-2 at 6 Months in Patient 1011 baseline 3 months 6 months 10 9 8 7 6 5 4 3 2 1 0 DSC2 positive cardiac tissue (%) baseline 3 months 6 months 10 9 8 7 6 5 4 3 2 1 0 CDH2 positive cardiac tissue (%) baseline 3 mon
Slide 14: RP-A601 Increases Desmosomal Proteins & Cadherin-2 in Patient 1010
14 Data cutoff April 2025. RP-A601 Increases Expression of Desmosomal Proteins & Cadherin-2 at 3 and 6 Months in Patient 1010 baseline 3 months 6 months 10 9 8 7 6 5 4 3 2 1 0 PKP2 positive cardiac tissue (%) baseline 3 months 6 months 10 9 8 7 6 5 4 3 2 1 0 CDH2 positive cardiac tissue (%) baseline
Slide 15: Stabilization or Improvement in RV Function, QoL, and NYHA Class
15 Stabilization or Improvement in RV Function, QoL, and NYHA Class at Most Recent Visit Patient ID Age at Enrollment (y) Most Recent Visit (MRV, mo) RV Systolic Function (ECHO) BL MRV KCCQ-12 Score BL MRV (% change) NYHA Class BL* MRV 1003 55 12 Normal Normal† 39.6 74.0 (+87%) II I 1011 58
Slide 16: Preliminary Indications of Improvement in Clinical Markers of Arrhythmia Burden
16 Preliminary Indications of Improvement or Stabilization Observed in Clinical Markers of Arrhythmia Burden Patient ID Age at Enrollment (y) Most Recent Visit (MRV, mo) PVCs per 24h BL MRV (% change) NSVT Episodes per 24h BL MRV T-wave inversions (precordial and inferior ECG) 1003 55 12 117* 4
Slide 17: Summary of Initial Results From Ongoing Phase I Trial
Summary of Initial Results From Ongoing Phase I Trial Cohort 1 Patients with PKP2-ACM Treated with RP-A601 Demonstrated RP-A601 was generally well-tolerated with no dose-limiting toxicities observed No TMA or ventricular arrhythmias were observed Increased expression and desmosomal localization of P
Slide 18: Key Findings and Path Forward
Key Findings and Path Forward Key Findings RP-A601 was generally well tolerated in all 3 patients SAEs were reversible without clinical manifestations, no dose-limiting toxicities observed All 3 patients in Cohort 1 demonstrated cardiac transduction with localized myocardial protein expression that
Slide 19: Thank You
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