Slide 1: RP-A501 Program Update
Si * RP-A501 Program Update® November 2024
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 wells assumptions that, ifthey do not materialize or prove incorrect, could cause our results to differ materaly fr
Slide 3: Danon Disease
Danon Disease X-linked monogenic disease™* + LAMP2 gene variants + Impaired autophagy + Prominent sarcoplasmic vacuoles ‘+ Myofibrillar disarray Severe Cardiomyopathy!37 ‘+ Mortality secondary to heart failure or arrhythmia + Males: = Hypertrophic phenotype with arrhythmias + Left Ventricle (LV) hyp
Slide 4: Rapidly Progressive Cardiomyopathy with Early Mortality in Males
Rapidly Progressive Cardiomyopathy with Early Mortality in Males Males: Critical interval in childhood/ Limited Overall Survival'* early adolescence precedes rapid decline! Gene Therapy 10 (hypothesized optimal treatment juncture) $ Symptoms = 08 8 Diagnosis 3 8 Accderte 508 5 progression to 3 5 cnd
Slide 5: AAV Gene Therapy for Danon Disease: RP-A501
AAV Gene Therapy for Danon Disease: RP-A501 Goal ‘Schematic Representation of RP-ASO1 (AAV9.LAMP2B) + Restore LAMP28 protein expression aave + Restore autophagy + Normalize myocardial structure and function Intravenous administration of RP-ASO1 * RP-ASO1: rAAVS capsid with DNA encoding full-length L
Slide 6: Phase 1 Study Overview
Phase 1 Study Overview Safety and Preliminary Efficacy Follow-up for RP-A501 Out to 24-54 Months * Cohort 1: Low Dose Inclusion Criteria | guit/adolescent(n-3) 1002 + Males age 28 years Vv ed ——— + LAMP2 variant Cees FE —SSSSS ————— =p EEE ED * Cardiac involvement lM regimen: Steroid + Tacrolimus (i
Slide 7: Baseline Characteristics
Baseline Characteristics Marked LV Hypertrophy, Elevated Biomarkers and Symptoms of Disease 6.7 x10 GC/ke 1.110 GC/kg 67 x10" GC/ke ‘Adult/adolescent, N=3 ‘Adult/adolescent, N=2* Pediatric, N=2 Clinical Characteristics Patient 00 i002 1005 006 1007 008 008 ‘Age at infusion, y 175 204 183 aa 207 23 u
Slide 8: Treatment-Emergent Severe Adverse Events
Treatment-Emergent Severe Adverse Events 167 x10 GC/ke ‘Adult/adolescent 11x10 GC/kg Adult/ad 6.7 «108 GC/ke Favorable Safety Profile with Enhanced Immunomodulation Protocol Low Dose Adult/Adolescent Cohort: = One instance each of AST/ALT elevation, pyrexia and nausea/vomiting related to drug produc
Slide 9: Positive and Sustained LAMP2 Expression in Endomyocardial Biopsies
Positive and Sustained LAMP2 Expression in Endomyocardial Biopsies Durable myocardial LAMP2 protein expression seen in all patients Myocardial LAMP2 Protein Expression Representative LAMP2 IHC Images Cohort Patient BL_M6 M12 Mis M24 M30 M36 _M6OF UUNIReeacce UE avai mmo 1001 we a sdunfacecent 1002 e
Slide 10: Reduction in Autophagic Vacuoles
Reduction in Autophagic Vacuoles Representative H&E Staining and EM Images from Endomyocardial Biopsies Representative Images from the Endomyocardial Biopsy of Patient 1008 42 months
Slide 11: Improvement or Stabilization from Baseline in Key Efficacy Parameters
Improvement or Stabilization from Baseline in Key Efficacy Parameters Agest © Most LVEF © ALVML* —AIVSd, ALVPWd, ANT-proBNP, Anyua 4KCCQ42 IConort Patient MostRV Recent BL>RV BL>RV BL>RV BLIRV BL>RV pti () _ Visit(mo) —(%) (gm?) (mm) (mm) (ng) 33%, 6%, -20%, “17%, 99% = +52, i Se 54 187264 | ae ocs0
Slide 12: Sustained Improvements in LV Mass Index Observed in All Patients
Sustained Improvements in LV Mass Index Observed in All Patients LVMI % Change from Baseline LVMI % Change: Baseline to 12m* ,S mi or re rs me 1001" 1002 1005 1008 1009" eee FS FC EEL LE = = gaa@ ee | “a ES ns —_ 10% LvMI% chant 8 Baseline to Most Recent Visit* 001% s00s* 1008-1009" 1% 10% 20% 50% |
Slide 13: Sustained Reductions in Circulating Cardiac Troponins
Sustained Reductions in Circulating Cardiac Troponins Cardiac Troponin-I Levels® Pre- and Post-RP-ASO1 (ng/mL) 2.00 1001 1.80 1002 1.60 1005 1.40 1005 120 1008 1.00 1009 0.80 0.60 0.40 0.20 ue 0.00 Baseline maz was m4 M30 36 maz mas ictnot conucte.ancrnss png runner nei ta town ee lew perme on ighen
Slide 14: Phase 1 Study of RP-A501: Summary of Results
Phase 1 Study of RP-A501: Summary of Results Favorable Benefit-Risk Profile for RP-A501 Key Findings * RP-A5O1 was generally well tolerated with a transient immunomodulatory regimen of rituximab, sirolimus, and corticosteroids = All SAEs were reversible without sequelae, and all patients are alive +
Slide 15: Thank You
Thank You