Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — 41st Annual J.P. Morgan Healthcare Conference (January 2023)
45 slides from Rocket Pharmaceuticals's conference presentation, Jan 9, 2023
Slide 1: 41st Annual J.P. Morgan Healthcare Conference Presentation
INVESTOR DECK INVESTOR 41st Annual DECK J.P. Morgan Healthcare INVESTOR Conference Company DECK Presentation Gaurav Shah, MD Chief Executive Officer January 9, 2023
Slide 2: Disclaimer
DISCLAIMER Various statements in this presentation concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding its guidance for 2023 in light of COVID-19, the safety, effectiveness and timing of product candidates that Rocket may develo
Slide 3: Vision: Seeking Gene Therapy Cures
ABOUT ROCKET PHARMACEUTICALS Vision: Seeking Gene Therapy Cures Values Mission To develop first-in-class and best-in-class curative v Curiosity gene therapies for patients Trust Elevate with devastating diseases Generosity 3
Slide 4: Generating Value-based Gene Therapies
ABOUT ROCKET PHARMACEUTICALS Generating Value-based Gene Therapies Therapeutic area focus: Promising top-line clinical data designed Late-stage Heart and bone marrow to facilitate US and European registration science and Only company with safety and and launch with potential???? for expansion innova
Slide 5: Strong Science, Carefully-selected Assets and Smart Execution
ABOUT ROCKET PHARMACEUTICALS Strong Science, Carefully-selected Assets and Smart Execution: 6 Disclosed programs with compelling clinical and/or pre-clinical proof of concept Criteria used to 6+ programs with 2 programs fast approaching regulatory filing and launch select programs THERAPEUTIC PHASE
Slide 6: Rocket Offers Multi-platform Gene Therapy Expertise
ABOUT ROCKET PHARMACEUTICALS Rocket Offers Multi-platform Gene Therapy Expertise IN VIVO platform EX VIVO platform Laboratory- Remove cells Laboratory- produced AAV and isolate produced LV patient HSCs Therapeutic Therapeutic LV AAV Infusion Direct intravenous of modified injection HSCs Gene-modifie
Slide 7: Looking Forward to a Catalyst-Rich 2023
ABOUT ROCKET PHARMACEUTICALS Looking Forward to a Catalyst-Rich 2023 Transition from Clinical to Commercial Stage 2023 2024 Q1 Q2 Q3 Q4 • Completed 2 • Planned Danon Phase • Danon EU IMPD • FA Product Filing • BAG3 IND Filing In-house 2 Study Initiation Filing • PKD Phase 2 Pivotal • FA (C & G) IND
Slide 8: Danon Disease (DD): Serious Condition with Unmet Medical Need
RP-A501: Danon Disease Danon Disease (DD): Serious Condition with Unmet Medical Need Disease Etiology Therapeutic Challenges • X-linked, dominant, • Standard of care: monogenic disease o Heart transplant (HTx) • Loss-of-function • Limitations: mutations in LAMP2 o Considerable morbidity and mortalit
Slide 9: Phase 1 Study: Treatment Completed
RP-A501: Danon Disease Phase 1 Study: Treatment Completed Non-randomized open label study in male DD patients Single intravenous dose of RP-A501 (AAV9.LAMP2B) delivering full coding sequence of the LAMP-2B gene PRIMARY OUTCOMES Pediatric **Enrollment Complete** Time of follow- • Early and long-term
Slide 10: RP-A501 Demonstrates Favorable Safety Profile With Enhanced Immunomodulation Protocol
RP-A501: Danon Disease RP-A501 Demonstrates Favorable Safety Profile With Enhanced Immunomodulation Protocol ADULT COHORT PEDIATRIC COHORT (Low dose) All SAEs observed within initial 2-4 No RP-A501–related SAEs months following dosing; reversible All AEs were transient and reversible, with 8 with su
Slide 11: Pediatric LAMP2 Protein and DNA Suggests Durable Expression
RP-A501: Danon Disease Pediatric LAMP2 Protein and DNA Suggests Durable Expression As Demonstrated in Adult Cohort LAMP2 Protein Expression Cardiac LAMP2 DNA by qPCR 1001 4 1002 (vector copies per diploid nucleus) 1005 1006 Patient ID Predose Month 6 Month 12 Month 36 3 1008 1001† 0 0.384 0.197 0.12
Slide 12: Improvement or Stabilization Across Key Biomarkers, Echo and Functional Measures
RP-A501: Danon Disease Improvement or Stabilization Observed Across Key Biomarker, Echo Findings and Functional Measures in Phase 1 RP-A501 Study Most recent Δ LV max wall Δ NYHA Δ KCCQ Cohort Patient ID visit (months) Δ hsTnI Δ BNP Δ LV mass thickness class score 1008 12 ↓86% ↓83% ↓29%1 ↓15%1
Slide 13: Improvement or Stabilization Observed Across Key Cardiac Biomarkers
RP-A501: Danon Disease Improvement or Stabilization Observed Across Key Cardiac Biomarkers BNP (pg/mL) Troponin-I (ng/mL) 2000 2.00 1800 1.80 1600 1.60 1400 1.40 1200 1.20 1000 1.00 800 0.80 600 0.60 400 0.40 200 0.20 0 0.00 BL M9 M12 M18 M24 M30 M36 BL M9 M12 M18 M24 M30 M36 1001 1002 1005 1006 100
Slide 14: RP-A501 Phase 1 Patients: Marked Divergence from Natural History
RP-A501: Danon Disease RP-A501 Phase 1 Patients: Marked Divergence from Natural History in Key Biomarkers RP-A501 Phase 1 Baseline & Timepoints ≥6 months Sample Pediatric and Adolescent External Comparators 3200 3200 1010: Received HTx ~2M following this timepoint #9: Entered Ph1 #3: Entered Ph1 280
Slide 15: NYHA Class in Danon Disease Male Patients: Natural History versus RP-A501
RP-A501: Danon Disease NYHA Class in Danon Disease Male Patients: Natural History versus RP-A501 Phase 1 Prospective Natural RP-A501 Phase 1 Treated History Cohort1 Patients (LVEF>40%) Prospective Natural History: • No patients had improved NYHA Class Improvement RP-A501: ≥ 1 NYHA Class • All patien
Slide 16: Insights from Danon Disease Patients Treated on the Phase 1 Trial
RP-A501: Danon Disease Insights from Danon Disease Patients Treated on the Phase 1 Trial He can walk upstairs without being short of breath or having to stop half-way. He doesn’t have chest pain Prior to therapy, he was afraid of dying and or fast heart rates like he used to. Another amazing wanted
Slide 17: Projected Pivotal Study Design
RP-A501: Danon Disease Projected Pivotal Study Design Key Agreements Reached with FDA Elements in Discussion Additional Study Elements • Will utilize revised Phase I 6.7x1013 GC/kg dose eligibility criteria (i.e. LVEF • Specific components of composite >50%) Single-arm, open-label study endpoint
Slide 18: Robust Ongoing Natural History Efforts to Support External Comparator
RP-A501: Danon Disease Robust Ongoing Natural History Efforts to Support External Comparator Sample Prospective Natural History Study US Retrospective Natural History EU Retrospective Natural History Study 9 1 51 67 Males (goal 60) Females (goal 60) Males Female Males Females Initiated in 2019, expa
Slide 19: In-House Manufacturing to Support Danon Pivotal Study and Commercial Production
RP-A501: Danon Disease In-House Manufacturing to Support Danon Pivotal Study and Commercial Production • 2 Successful Danon AAV cGMP batches produced in Q4 2022 • Superior specifications to Phase I material; allow for full dosing with lower total viral particles, potentially further improving safety
Slide 20: Cranbury R&D and Manufacturing Facility Overview
RP-A501: Danon Disease Cranbury R&D and Manufacturing Facility Overview • Total Lab Space: ~30,000 sq. ft. for process development, analytical development, MS&T and QC • Manufacturing capability from small-scale to toxicology-scale material • Streamlined tech transfer timeline for pipeline assets fr
Slide 21: Development Plan
RP-A501: Danon Disease Development Plan Moving toward pivotal global Phase 2 study Study Milestones Ongoing Activities Phase 1 treatment completed in • Final Phase 2 Study Design and Endpoints males • Initiate Phase 2 Global Pivotal Study Activities GLOBAL Orphan Drug, Rare Pediatric and REGISTR
Slide 22: RP-L102 for Fanconi Anemia Complementation Group A (FA-A)
RP-L102: Fanconi Anemia RP-L102 for Fanconi Anemia Complementation Group A (FA-A) Disease etiology Therapeutic challenges • FA-A is an autosomal Standard of care: recessive disease • Allogeneic HSCT caused by FANCA Limitations: gene mutations • Significant toxicities, especially for • FA proteins en
Slide 23: Progressively Increasing and Sustained Genetic Correction in 7 of 10 Patients
RP-L102: Fanconi Anemia Progressively Increasing and Sustained Genetic Correction in 7 of 10 Patients ≥1 Year Post–RP-L102 Progressive increases in gene markings in PB and BM in 7 patients PBMC VCN BM VCN VCN in peripheral blood VCN in bone marrow mononuclear cells mononuclear cells VCN in bone marr
Slide 24: Increasing Phenotypic Correction (MMC-resistance) over 1 to 3 Years
RP-L102: Fanconi Anemia Increasing Phenotypic Correction (MMC-resistance) over 1 to 3 Years Post–RP-L102 Sustained BM CFC MMC resistance observed in at least 6 patients* 12m post gene therapy For 5 patients, increased BM CFC MMC resistance ranging from 51% to 94% was observed at 18 to 24 months post
Slide 25: Development Plan: Moving toward BLA/MAA filing
RP-L102: Fanconi Anemia Development Plan Moving toward BLA/MAA filing INITIAL EFFICACY AND HIGHLY TOP-LINE DATA READOUT NEXT STEPS FAVORABLE SAFETY PROFILE ACHIEVED • Update: CMC and clinical FDA discussions support BLA activities • Initial comprehensive efficacy • Rejection of null hypothesis with
Slide 26: RP-L201 for LAD-I: ITGB2 Gene Mutation
RP-L201: LAD-I RP-L201 for LAD-I: ITGB2 Gene Mutation Disease etiology Therapeutic challenges • ITGB2 gene mutations Standard of care: (21q22.3), encoding the • Allogeneic HSCT beta-2-integrin, CD18; Limitations: essential for leukocyte • Donor availability adhesion to endothelium • Infections • CD1
Slide 27: CD18 Expression in PB Polymorphonuclear Cells (PMNs)
RP-L201: LAD-I CD18 Expression in PB Polymorphonuclear Cells (PMNs) At 3 to 24 months after infusion, 9/9 patients sustained stable CD18 expression (median: 56%) with no therapy-related serious adverse events * *Dim/weak CD18 expression reported at baseline for Subject L201-003-1004 in ~63% of cells
Slide 28: Significant Reduction in Hospitalizations and 100% Overall Survival
RP-L201: LAD-I Significant Reduction in Hospitalizations and 100% Overall Survival 100% overall survival Kaplan–Meier estimate Significant reduction in incidence of hospitalizations Survival without allogeneic HSCT Post engraftment Primary outcomes • ≥2 years of age AND All patients have been able t
Slide 29: Development Plan: Moving toward product filing
RP-L201: LAD-I Development Plan Moving toward product filing ENROLLMENT AND TOP-LINE DATA READOUT NEXT STEPS INITIAL EFFICACY Q2 2022 • Progression to regulatory • Enrollment completed; filing activities • Survival for 9/9 patients, ≥2 years 9/9 patients treated age and ≥1 year post-treatment • Effi
Slide 30: RP-L301 for PKD: PKLR Gene Mutation
RP-L301: PKD RP-L301 for PKD: PKLR Gene Mutation Disease etiology Therapeutic challenges • Autosomal recessive • Standard of care: Chronic blood inheritance transfusions and splenectomy • Pyruvate kinase • Limitations: deficient RBCs o Iron overload cannot synthesize o Extensive end-organ damage ATP
Slide 31: Preliminary Efficacy Results for Patients L301-006-1001 and L301-001-1002
RP-L301: PKD Preliminary Efficacy Results for Patients L301-006-1001 and L301-001-1002 Hemoglobin improvement to normal range (from baselines in severe (<8 g/dL range) Transfusion independence (extensive transfusion requirements prior to RP-L301) Sustained improvement of hemolysis markers (LDH, bili
Slide 32: Development Plan: Moving toward pivotal Phase 2 study
RP-L301: PKD Development Plan Moving toward pivotal Phase 2 study PLAN FOR PHASE 2 AND LAUNCH Key endpoints selected LIFE-CYCLE • Hemoglobin increase MANAGEMENT • ↓ 50% in transfusions or transfusion independence • Anticipated expansion Well-delineated natural history in recent PKD NHS publications
Slide 33: Future Therapies: Wave 2 (AAV)
FUTURE DIRECTIONS Future Therapies: Wave 2 (AAV) Focused R&D Strategy for Current Clinical Sustainable Innovation Pipeline First-, best- and/or only-in-class On-target MOA; clear endpoints Sizeable market to maximize patient impact 3 therapeutic areas (CV, heme and undisclosed) We continue to build
Slide 34: BAG3 Regulates Critical Functions in Cardiomyocytes
BAG3 Dilated Cardiomyopathy BAG3 Regulates Critical Functions in Cardiomyocytes Cardiac contractility Protein quality control Enhances contractility by linking Facilitates autophagy as a co- the β-adrenergic receptor and chaperone with heat shock L-type Ca2+ channel proteins, recycling misfolded pro
Slide 35: BAG3-DCM Opportunity and Next Steps
BAG3 Dilated Cardiomyopathy BAG3-DCM Opportunity and Next Steps BAG3-DCM Represents a Significant Market Initial Proof-of-Concept for AAV9-BAG3 Supports with Unmet Need Further Development • Dilated cardiomyopathy (DCM) is the most common • Initial proof of concept for AAV9-BAG3 form of cardiomyopat
Slide 36: Project Pegasus (PKP2-ACM)
Project Pegasus (PKP2-ACM) 36
Slide 37: PKP2-Arrhythmogenic Cardiomyopathy (ACM): A high-risk disease with no curative options
RP-A601: PKP2-ACM PKP2-Arrhythmogenic Cardiomyopathy (ACM)*: A high-risk disease with no curative options Advanced ACM Heart with Disease Etiology Therapeutic Challenges fibrofatty replacement in right ventricle • Autosomal dominant mutations • Current standard of care includes beta- in PKP2 gene, w
Slide 38: PKP2-ACM Prevalence in the US and EU
RP-A601: PKP2-ACM PKP2-ACM Prevalence in the US and EU ACM prevalence 1:1000 to 1:5000 Peters 2004, McKenna 2021 PKP2 variants 2,572 ACM patients assessed from 13 publications an aggregated 32.9% mean of 32.9% had PKP2 mutations1 Utilizing the conservative ACM ACM-PKP2 US & EU Prevalence prevalence
Slide 39: Proof of Concept in Translationally Relevant Animal Model
RP-A601: PROGRAM PKP2-ACM 4: RP-L301 for PKD Proof of Concept in Translationally Relevant Animal Model Completed RCKT Studies with Cardiomyocyte-specific PKP2 Knockout Mouse Model of ACM • Initial POC evaluated 4 AAV Vectors: Cardiac Functional & Structural Analyses • Dose-related effects evaluated
Slide 40: Tamoxifen-induced ACM in the PKP2-cKO Mouse Model
RP-A601: PKP2-ACM Tamoxifen-induced ACM in the PKP2-cKO Mouse Model • The PKP2-cKO mouse model recapitulates ACM following induction of PKP2 KO by tamoxifen (TAM) injection • Progression of cardiomyopathy evidenced by Masson’s trichrome staining of heart sections in PKP2-cKO mice from 14 to 42 days
Slide 41: Increased Survival & Preserved Cardiac Function in the PKP2-cKO Model
RP-A601: PKP2-ACM Increased Survival & Preserved Cardiac Function in the PKP2-cKO Model LVEF RV Area - AAV +7D Post-TAM AAV +7D Post-TAM AAV +7D post-TAM 80 8 AAVrh.74-PKP2a Dose 1 (n = 10) 28 D 5 Mo 28 D 5 Mo Control-FB (n = 9) 60 6 RV Area (mm2) * * LVEF (%) 40 4 * * 20 2 PKP2-cKO-FB (n = 10) (9)
Slide 42: Optimal Gene Therapy for PKP2-ACM, Expected to be First-and Best-In-Class
RP-A601: PKP2-ACM Optimal Gene Therapy for PKP2-ACM, Expected to be First-and Best-In-Class cDNA/isoform: • PKP2a: full wild type coding sequence of therapeutic gene, protein loss drives ACM AAV Serotype: • AAV.rh74 serotype associated with favorable safety profile in DMD/LGMD2E1-2; potential for sa
Slide 43: Clinical Development Plan
RP-A601: PKP2-ACM Clinical Development Plan Moving Toward Phase 1 Dose Escalation Study Completed or Ongoing Activities High Level Phase 1 Proposed Trial Design Natural History GMP drug product manufacturing • Study design: • To provide context completed • FIH, multi-center, 3+3 dose escalationa s
Slide 44: Rocket – The Leader in Rare Disease Gene Therapy
Rocket – The Leader in Rare Disease Gene Therapy Pre-eminent maturing gene therapy pipeline in which each program is First- and Best-in-Class Experienced management team with a history of delivering transformative and curative therapies to patients with devastating diseases Well-capitalized an
Slide 45: Thank You
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