S E E K I N G G E N E T H E R A P Y C U R E S Rocket Pharmaceuticals Danon Disease Program Update

S E E K I N G G E N E T H E R A P Y C U R E S Rocket Pharmaceuticals Danon

Disease Program Update September 11, 2023 1 CONFIDENTIAL AND PROPRIETARY

Disclaimer 1 CONFIDENTIAL AND PROPRIETARY Various statements in this

presentation concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding the safety and effectiveness of product candidates that Rocket is developing to treat Danon Disease (DD),

the expected timing and data readouts of Rocket's ongoing and planned clinical trials, the expected timing and outcome of Rocket's regulatory interactions and planned submissions, Rocket's plans for the advancement of its Danon Disease program,

including its planned pivotal trial, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private

Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as

"believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected

in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without

limitation, Rocket's ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rocket's

ongoing trials, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of

pre-clinical studies and clinical trials of its product candidates, our ability to submit regulatory filings with the U.S. Food and Drug Administration (FDA) and to obtain and maintain FDA or other regulatory authority approval of our product

candidates, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, our competitors' activities, including decisions as to the timing of competing

product launches, pricing and discounting, our integration of an acquired business, which involves a number of risks, including the possibility that the integration process could result in the loss of key employees, the disruption of our

ongoing business, or inconsistencies in standards, controls, procedures, or policies, our ability to successfully develop and commercialize any technology that we may in-license or products we may acquire and any unexpected expenditures, as

well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket's Annual Report on Form 10-K for the year ended December 31, 2022, filed February 28, 2023 with the SEC and subsequent filings with the SEC including our

Quarterly Reports on Form 10-Q. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any

forward-looking statements, whether as a result of new information, future events or otherwise.

Danon Disease Aggressive genetic hypertrophic cardiomyopathy with very high early

mortality Danon Disease is the most aggressive and lethal hypertrophic cardiomyopathy Monogenic, X-linked disease progresses to severe cardiomyopathy at early ages; characterized by massive LV hypertrophy and end-stage heart

failure Uniformly fatal with early mortality (males ~19 yrs.; females ~37 yrs.) Only definitive treatment is cardiac transplantation, availability is limited, and associated with extensive short- and long-term morbidity and mortality (<50%

10-yr survival post HTx) Estimated prevalence of 15,000 to 30,000 individuals and annual incidence of 800 to 1,200 individuals in US & EU In July 2023, US Dept. Health and Human Services approved IDC 10 Code for DD (E74.05) Gene

mutation leads to decreased LAMP2B protein and impaired autophagy Cenacchi G et al. Neuropathol. Appl. Neurobiol. 2020; Rowland T et al. J Cell Sci. 2016; Boucek D, Jirikowic J, Taylor M. Genet Med 2011; Thrush P et al. J Thorac Dis. 2014;

Dipchand A et al. J Heart Lung Transplant. 2014 Impaired autophagy leads to vacuoles, myocyte hypertrophy, necrosis, & fibrosis 1 2 3 Pathologic processes lead to phenotype of extreme LV hypertrophy and cardiomyopathy 4 Natural

History: High rates of death at early ages Females Males 3 3 CONFIDENTIAL AND PROPRIETARY

Natural History: Progression of Danon Disease in Male Patients Birth to 7

yrs NYHA Class I Muscle pain, lack of energy Learning difficulties HF symptoms (rare) Identification by incidental genetic testing or family history Death avg age: 19 years 8-14 yrs NYHA Class I-II HCM & genetic

diagnosis Worsening fatigue, Shortness of breath on mild exercise Palpitations, syncope, chest tightness Thickening heart, increasing NPs, troponins 15-19 yrs NYHA Class II-III Life-threatening ventricular arrhythmias ICD/pacemaker

placement Progression to end-stage cardiomyopathy Listing for heart transplant Significant increase in caregiver burden Thickening heart, increasing NPs, troponins, fibrosis; decline in LVEF Late Teens / Early Twenties Significant

cardiac dysfunction Heart failure Heart transplant / VAD (~20% of patients), comes with significant short- and long- term complications Anxiety, depression Unemployment Figure created based on data from Brambatti M et al. Int J Cardiol.

2019;286:92-98; Boucek D, Jirikowic J, Taylor M. Genet Med 2011; 13(6):563-68 CONFIDENTIAL AND PROPRIETARY 4 Critical interval in childhood / early adolescence precedes rapid decline, providing optimal window of opportunity for GTx Patients

typically on maximal medical management (e.g. beta blockers, ICD) - none alter disease progression Note: Danon disease is a life-threatening and seriously debilitating condition. Above are not meant to be a strict categorization of

symptoms/outcomes by age. Heart failure and death from Danon disease can occur well before the patient reaches his twenties. Of note, the four adult patients in the Phase 1 study with 2.5-3.5 yr follow-up post gene therapy are currently alive,

clinically stable, and free from Danon disease progression at ages 21-24 years old - in contrast to the trend in the natural history of this disease. NYHA = New York Heart Association Class; ICD: implantable cardioverter-defibrillator; HTx =

Heart Transplantation; VAD: Ventricular Assist Device

Phase 1 Data: Benefit Observed Across All Key Clinical Parameters Early LAMP2,

BNP, TnI changes associated with sustained clinical improvement and guided Phase 2 endpoint selection Does not include pt 1007 in Ph1 trial who had advanced HF with EF<40% at enrollment and received HTx 5M following tx due to pre-existing

advanced HF. Patient is currently stable. BNP, brain natriuretic peptide; hsTnI, high- sensitivity troponin I; KCCQ, Kansas City Cardiomyopathy Questionnaire; LAMP2, lysosome-associated membrane protein 2; LV, left ventricle; NYHA, New York

Heart Association. Data cut-off Oct 6, 2022; Grade 0=negative All specified parameters either improved or stabilized (none deteriorated) Improved Stabilized Worsened 5 CONFIDENTIAL AND PROPRIETARY staining; Grade 1 25%; Grade 2 =26%-50%;

Grade 3 =51%-75%; Grade 4 >75%. Low dose = 6.7x1013 GC/kg, high dose = 1.1x1014 GC/kg CONFIDENTIAL AND PROPRIETARY 5 Cohort Patient ID Follow-up (months) Myocardial LAMP2 Grade ( M12) TnI ( M12) BNP ( M12) LV mass

(g) LV Mass Index (g/m^2.7) Max LV Wall Thickness (mm) NYHA class KCCQ score Low dose adult/ adolescent 1001 36 1 -75% (M18) -36% 311 212 85 57 25 23 II II 44 49 1002 36 3 -79% -76% 989 511 260

129 64 38 II II 64 81 1005 30 2 (M9) -57% (M9) -64% (M9) 438 375 98 76 33 24 II I 77 85 (M24) High dose adult/ adolescent 1006 24 1 -47% -70% 410 300 90 63 22 18 II I 79 82 Low dose

pediatric 1008 12 1 -86% -83% 605 447 140 96 42 39 II I 50 82 1009 6 1 -90% -62% 234 185 83 63 20 20 II I 52 78

Latest Pediatric Data Shows Sustained Improvements in Biomarkers, Symptoms, and

Function (Updated Data) Variable Baseline2 Most Recent Follow-up LAMP2 protein3 0 1 (M6) Troponin-I (ng/mL) 0.67 0.08 (-88%) BNP (pg/mL) 297 163 (-45%) NYHA Class II I LV Mass Index 83 60 (-28%)4 12 months AGE AT

INFUSION 11.7 years ICD no WPW no Subject ID: A501-008-1008 Baseline Characteristics AGE AT INFUSION 12.3 years ICD yes1 WPW yes Variable Baseline2 Most Recent Follow-up LAMP2 protein3 0 1 (M12) Troponin-I

(ng/mL) 1.89 0.30 (-84%) BNP (pg/mL) 1837 328 (-82%) NYHA Class II I LV Mass Index 140 96 (-31%)4 18 months MAX LV WALL THICKNESS 41.9 mm, z-score +32 6MWT 438 meters MAX LV WALL THICKNESS 19.8 mm, z-score +12 6MWT 553

meters Subject ID: A501-008-1009 Baseline Characteristics 1 Recommended prior to enrollment; ICD implanted 3 months after RP-A501 infusion. 2 Baseline values for troponin-I and BNP are the mean values from all pre-dose visits. 3 Extent of

LAMP2 expression grading: Grade 0 = negative staining, Grade 1 < 25%, Grade 2 = 26-50%, Grade 3 = 51-75%, Grade 4 > 75%. 4M12 Note: All data preliminary, not yet validated. 6MWT, 6-minute walk test; BNP, brain natriuretic peptide; ICD,

implantable cardioverter defibrillator; KCCQ, Kansas City cardiomyopathy questionnaire; LAMP2, lysosome-associated membrane protein 2; LV, left ventricle; NYHA, New York Heart Association; WPW, Wolff-Parkinson-White

syndrome. 6 6 CONFIDENTIAL AND PROPRIETARY `

Pivotal, single-arm study Peds safety run-in Dosage (6.7x1013 GC/kg)

Safety protocol & management plan CMC (product comparability and potency assay) NHS to serve as external comparator RMAT designation granted F2F meeting with review team and senior FDA leadership Co-primary endpoint to support

accelerated approval consisting of LAMP2 expression & LV Mass reduction of 10% N=12 patients for pivotal study with potential for primary endpoint readout at 12 months Study to support AA with a path towards conversion to full

approval (with longer follow-up) FDA Engagement and Alignment on Danon Program Since the EOP1 Meeting in November 2022, Rocket has had collaborative formal and informal discussions with FDA to align on the optimal pivotal Phase 2 study

design Previously Disclosed Trial Elements Recent Engagement and Alignment 8 CONFIDENTIAL AND PROPRIETARY

Phase 2 Trial Design - 12 Patients with 12-month Primary Endpoint Duration Dose:

6.7 x 1013 GC/kg of commercially representative RP-A501 material Initial n=2 peds followed for 90 days for key AAV-associated toxicities prior to subsequent ped pt enrollment Key eligibility criteria: male age 8y, LAMP2 mutation, NYHA

II-III, evidence of LV hypertrophy, elevated hsTnI CO-PRIMARY ENDPOINT (AA) LAMP2 protein Grade 1 (IHC) AND Left Ventricular Mass (LV Mass): 10% SECONDARY & EXPLORATORY ENDPOINTS hs-troponin I (key secondary) Natriuretic

peptides QoL instruments (KCCQ, PedsQL, PGI-C, PGI-S) NYHA Class 6MWT Event free survival Treatment emergent safety events Actigraphy Tx, treatment; LV, left ventricular; NYHA; IDSMC, Independent Data Safety and Monitoring Committee;

hs-troponin I; KCCQ; HF; m, month; y, year; pts, patients Adolescent/Adult Cohort 15y End of Study 60m Primary Endpoint Assessment ~12m RISK MANAGEMENT PLAN, TRIAL OVERSIGHT Immunomodulatory regimen of Rituximab, Sirolimus,

corticosteroids. Clinical monitoring team to closely monitor labs, clinical sequelae for AAV-associated toxicities. IDSMC: expertise in adult and pediatric cardiomyopathy, immunology, and biostatistics RP-A501 Tx CONCURRENT NATURAL HISTORY

STUDY 90d (Additional pediatric dosing following Safety Run-in) Pediatric (8-14y) Safety Run-in (n=2) RP-A501 Tx Peds pt #1 Peds pt #2 1m Safety observation Pivotal, global, single-arm, open label study with external comparator PIVOTAL

PHASE 2 STUDY DESIGN 8 CONFIDENTIAL AND PROPRIETARY

9 HTx, heart transplant; LVEF, LVEF, left ventricle ejection fraction. US

Retrospective Natural History 9 Males 1 Female 51 Males 21 Males 38 Females Initiated in 2019, study complete Initiated in 2006 Enrollment complete; analysis in Q4 2023 67 Females Prospective Natural History Study EU

Retrospective Natural History Study To be expanded through an additional prospective Rocket-initiated natural history study Key Elements of Study Design: Entry criteria and endpoints similar to Phase 2 trial Appropriate matching to ensure

robust comparisons Retrospective data collection to supplement prospective evaluation to ensure sufficient comparative data Prospective, Retrospective Natural History Study as External Comparator Allows for robust comparisons and aligned

with FDA guidance 9 CONFIDENTIAL AND PROPRIETARY CONFIDENTIAL AND PROPRIETARY

10 Transplant-free survival Totality of Evidence to Demonstrate Treatment

Effect Baseline 12 Months 18 Months 24 Months Beyond 24-36 Months HF Hospitalizations Heart Transplant Death Phase 2 RP-A501 Treated Patients External Comparator Natural History (Untreated Patients) Each patient's baseline AND matched

external comparator arm together provide robust control data to assess treatment effect Improvement or stabilization of parameter Worsening of parameter Clinical Assessments Outcomes (Late ) Imaging & Biomarkers (Early )

(Intermediate ) External comparator arm serves as control at each timepoint CONFIDENTIAL AND PROPRIETARY Note: Illustrative representation of potential treatment effects versus natural history

Co-Primary Endpoints for Accelerated Approval 11 CONFIDENTIAL AND

PROPRIETARY CONFIDENTIAL AND PROPRIETARY

12 Primary Endpoint Is Reasonably Likely to Predict Clinical

Benefit Justification for use of LAMP2 protein expression and LV Mass Mutation of LAMP2 is root cause of Danon disease Epidemiologic support: even modest levels of LAMP2 confer a 2-decade survival advantage in female patients RP-A501

delivers full coding sequence of WT LAMP2 gene Pre-clinical LAMP2 restoration conferred histologic, functional and survival benefits in LAMP2 knock-out model1 Phase 1: LAMP2 expression associated with decreased vacuolar area, improved

myofibrillar disarray, clinical improvement WT Full Length LAMP2 Protein Expression Left Ventricular Mass Largest known hearts are Danon disease hearts Severity of the cardiomyopathy in Danon disease is the major prognostic

factor2 Retrospective natural history shows year-over-year increases in LV mass in Danon disease patients Phase 1: Consistent and significant reductions in LV mass as early as 6 months by echocardiography and cardiac MRI Primary Endpoint

Will Be Interpreted in a Clinical Context: All components are measurable and unlikely to improve in the absence of a true treatment effect Primary endpoint will be assessed in the context of biomarkers, symptoms, QOL, clinical events derived

from secondary endpoints and concurrent natural history study Phase 1 trial: LAMP2 expression and LV Mass improvements seen as early as 6 months in pediatric subjects with updated immunomodulation regimen 1 Manso 2020. Sci Transl Med.;

2D'souza 2017. J Community Hosp Intern Med Perspect. CONFIDENTIAL AND PROPRIETARY

Mechanistic Pathway: Protein Expression to Cardiac Structure to Clinical

Outcomes Improvements Across Cellular, Cardiac Imaging and Functional Measures in Phase 1 Study Molecular Expression Cellular Structure Cardiac Structure and Function Clinical Status Endomyocardial Bx: LAMP2 protein

expression Endomyocardial Bx: Vacuolar area Imaging & Biomarkers: LV Mass, Wall thickness, LVEF Troponin-I, BNP Functional parameters: NYHA Class KCCQ Overall Score Patient Screening Month 3 Month 6 Month 24 Month

36 Predose (Baseline) RP-A501 Note: BNP, brain natriuretic peptide; Bx, biopsy; KCCQ, Kansas City cardiomyopathy questionnaire; LAMP2, lysosome-associated membrane protein 2; LV, left ventricle; LVEF, LV ejection fraction; LVPWd, LV

posterior wall end diastole; MLVWT, maximal LV wall thickness; NYHA, New York Heart Association LAMP2 expression and LV Mass are mechanistically linked to functional measures and clinical outcomes; reasonably likely to predict clinical

benefit Month 9 Month 12 Month 18 Post Gene Therapy 1 2 3 4 13 13 CONFIDENTIAL AND PROPRIETARY

LAMP2 mutation and associated protein deficit is the root cause of Danon disease

pathology Grade 1 LAMP2 correlates with evidence of efficacy in Ph1 Absent expression at baseline (Grade 0) in all male patients Improved cardiac biomarkers & hypertrophy, PRO/QOL and NYHA Class - sustained to 3+ years in adult

patients, and 12+ months in pediatric patients Efficacy consistent in patients with Grade 1 vs. Grade >1 LAMP2 expression Ph1 expression correlates with autophagic vacuoles and improved myofibrillar disarray, cardiac biomarkers and

hypertrophy In Danon females, partial LAMP2 expression associated with ~2 decade longer survival than males LAMP2 Protein Expression as Co-Primary Endpoint RP-A501 encodes full-length, wild-type LAMP2B; cardiomyocytes are non-dividing

cells 14 CONFIDENTIAL AND PROPRIETARY

Rocket AHA 2022 Poster Presentation reflects September 27, 2022 data cutoff.

LAMP2, lysosome associated membrane protein 2; M, month. IHC = immunohistochemistry RP-A501 Increases LAMP2 Protein and Decreases Vacuolization Enhanced autophagy leads to improved myocardial ultrastructure and clinical phenotype Myocardial

LAMP2 Protein Expression Endomyocardial Biopsy Images (Subject 1008, RP-A501 Phase 1 Study) Vacuolar Area of Endomyocardial Tissue 15 CONFIDENTIAL AND PROPRIETARY 15 CONFIDENTIAL AND PROPRIETARY

Left Ventricle Mass as Co-Primary Endpoint Danon Disease is fundamentally a

disease of enlarged hearts; the largest known hearts have been from Danon patients Left ventricular hypertrophy is the most consistent phenotypic feature of disease progression Left ventricular wall thickness has been shown to be a

significant predictor of CV events in cardiomyopathy Meaningful LV Mass decreases seen as early as 6-9M in Phase 1 pediatric cohort, and LV Mass Index decreases sustained to up to 36M in adult patients; stark contrast to natural history In