Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — Investor Presentation (May 2022)
50 slides from Rocket Pharmaceuticals's investor presentation, May 20, 2022
Slide 1: Rocket Program Updates Following ASGCT 2022
Rocket Program Updates Following ASGCT 2022 Danon Disease, Pyruvate Kinase Deficiency, Fanconi Anemia, and Leukocyte Adhesion Deficiency-I Gaurav Shah, MD Chief Executive Officer May 20, 2022 SEEKING GENE THERAPY CURES 1 NASDAQ: RCKT
Slide 2: Cautionary Statement Regarding Forward-Looking Statements
Cautionary Statement Regarding Forward-Looking Statements Various statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding its guidance for 2022 in light of COVID-19, the safety, effectiveness and timing of
Slide 3: Rocket Pharma: Seeking Gene Therapy Cures
Rocket Pharma: Seeking Gene Therapy Cures 4 of 4 programs w/ compelling clinical proof of concept Multi-Platform Gene Therapy Company First, Best and Only-in-Class Clear MOAs and clinical endpoints Value-based and cost-effective pricing strategy; targeting fatal and serious diseases with Strong Comm
Slide 4: Our Multi-Platform Pipeline: Potential for Significant Value Creation
Our Multi-Platform Pipeline: Potential for Significant Value Creation Near and Long Term U.S. BLA/EU DISCOVERY PRECLINICAL PHASE 1 PHASE 2 (Pivotal) DESIGNATIONS MAA Filing Fast Track, Orphan AAV RP-A501 Danon Disease Drug (U.S.), Rare Pediatric Designation RMAT, ATMP, Fast Track, LV RP-L102 Fanconi
Slide 5: Danon Disease: A Monogenic Heart Failure Syndrome
Danon Disease: A Monogenic Heart Failure Syndrome RP-A501 RP-L301 RP-L102 RP-L201 Danon Disease Pyruvate Kinase Deficiency Fanconi Anemia Leukocyte Adhesion Deficiency-I Background: Multisystemic disorder caused by highly MECHANISM OF ACTION penetrant, X-linked dominant LAMP2 mutations; progressive
Slide 6: How Does rAAV Gene Therapy (RP-A501) Work in Danon Disease?
How Does rAAV Gene Therapy (RP-A501) Work in Danon Disease? Intravenous Administration of rAAV • AAV9 demonstrates tropism to: • Cardiomyocytes • Skeletal muscle • Brain tissue • Non-dividing, terminally differentiated cardiomyocytes can be transduced • rAAV9 DNA expresses LAMP2B gene • Cardiomyocyt
Slide 7: Danon Disease
Danon Disease Autosomal dominant, monogenic X-linked disease • LAMP-2B gene mutation (Lysosomal Associated Membrane Protein 2B) • Impaired autophagy • Prominent sarcoplasmic vacuoles • Myocardial disarray Females Severe Cardiomyopathy (CM 95%) • Mortality secondary to heart failure • Males: Males •
Slide 8: RP-A501: Gene Therapy Has Potential to Alter Natural History of Danon Disease Patients
RP-A501: Gene Therapy Has Potential to Alter Natural History of Danon Disease Patients Trajectory of cardiac pathophysiology and heart failure in male Danon disease patients Gene Therapy (hypothesized optimal treatment juncture) symptom onset diagnosis Cardiac Pathophysiology Stabilization or Improv
Slide 9: RP-A501: Danon Disease Gene Therapy Clinical Trial Overview
RP-A501: Danon Disease Gene Therapy Clinical Trial Overview Design Key Patient Entry Criteria** • Male Danon Disease patients Inclusion Non- • Adults (& Adolescents): >15 years • Male Randomized • Pediatric: 8-14 years • Confirmed LAMP2B mutation Open Label • Cardiac involvement confirmed by imaging
Slide 10: RP-A501: Baseline Status of Adult Cohorts
RP-A501: Baseline Status of Adult Cohorts Age at Clinical Status Cardiac Status Weight Cohort Patient ID Enrollment Six Minute LV Ejection (kg) BNP (years) NYHA Class Walk Fraction* (pg/mL) (meters) (%) 1001 17.5 52.5 II 443 70 62 Adult - Low Dose 1002 20.4 89.1 II 405 942 59 6.7 x 1013
Slide 11: RP-A501: LAMP2 Cardiac Protein Expression by Immunohistochemistry
RP-A501: LAMP2 Cardiac Protein Expression by Immunohistochemistry and Myofibrillar Structure by Electron Microscopy Normal Control Baseline* Month 9* Immunohistochemistry Electron Microscopy *Representative images from patient 1005 from endomyocardial. 11
Slide 12: RP-A501: Remodeling of Left Ventricular Hypertrophy in Adult Cohorts
RP-A501: Remodeling of Left Ventricular Hypertrophy in Adult Cohorts Septum Thickness Posterior WallPosterior ThicknessWall (LVPWd) Thickness Septum Thickness (IVSd) (IVSd) Ejection Fraction (LV EF) (LVPWd) 40 Posterior Wall (End-Diastole) 40 1001 % Change from baseline % Change from baseline Septum
Slide 13: RP-A501: Functional Clinical Status of Adult Cohorts
RP-A501: Functional Clinical Status of Adult Cohorts Most Recent Cohort Patient ID Variable Baseline Time of Follow-up Follow-up NYHA class II II 1001* 24 Months BNP (pg/mL) 70 30 Adult – NYHA class II I 1002 18 Months Low Dose BNP (pg/mL) 942 200 NYHA class
Slide 14: RP-A501: Serious Adverse Events in Adult Cohorts
RP-A501: Grade 3 and 4 Serious Adverse Events (SAEs) in Adult Cohorts (As Previously Disclosed) RP-A501 Related*: Thrombotic microangiopathy (TMA) [grade 4] associated with Pt 1007 (received highest dose • thrombocytopenia [grade 4] secondary to baseline weight and • acute kidney injury & renal fail
Slide 15: RP-A501: Risk Mitigation Strategies Implemented Prior to Pediatric Enrollment
RP-A501: Risk Mitigation Strategies Implemented Prior to Pediatric Enrollment Enhanced prophylactic immunosuppressive regimen • Sirolimus to inhibit complement activation • Steroid-sparing regimen to decrease skeletal myopathy • Initial dose 0.5 to 0.8 mg/kg/day (compared to > 1mg/kg/day in adult co
Slide 16: RP-A501: Immunosuppression, Patient Characteristics & Safety in Phase 1
RP-A501: Immunosuppression, Patient Characteristics & Safety in Phase 1 Cohort 1: Low-dose adult RP-A501 SAEs of Interest Platelets Pt Age Wt 6.7 x 1013 GC/kg n=2 grade 3 steroid myopathy n=2 decreases 1001 17.5 52.5 Steroid (prednisone 1mg/kg) to LLN range 1002 20.4 89.1 1005 18.3 91.8 Tacrolimus C
Slide 17: RP-A501: Inhibition of Complement Activation with Modified Immunosuppression
RP-A501: Inhibition of Complement Activation with Modified Immunosuppression Low Dose Adult High Dose Adult Low Dose Pediatric Corticosteroids Rituximab + Corticosteroids + Tacrolimus Rituximab + Corticosteroids + Sirolimus 2000 1001 (no data) 2000 1008 2000 1006 sC5b9 (mg/mL) sC59b 1002 1009 sC5b9
Slide 18: RP-A501: Summary of Results from Adult and Pediatric Cohorts
RP-A501: Summary of Results from Adult and Pediatric Cohorts Adult Cohort: Pediatric Cohort: RP-A501 was well tolerated in both • RP-A501 was generally well patients with modified protocol tolerated • T- and B-cell directed immunosuppression associated • Increased LAMP2 protein with markedly reduced
Slide 19: RP-A501: Conclusion and Future Direction
RP-A501: Conclusion and Future Direction • RP-A501 was generally well tolerated in adult and pediatric patients with Danon disease • Modified immunosuppressive regimen appears well tolerated and effective in pediatric cohort • Phase 1 efficacy signal in age ≥15 cohort: RP-A501 stabilizes and potenti
Slide 20: RP-A501: Overview of Development Plan
RP-A501: Overview of Development Plan ✓ Adult High- and Low-dose cohorts completed Current Status ✓ First patient dosed in pediatric cohort Additional Life-cycle Management Activities: ➢ Potential label expansion to include female Danon ✓ Orphan Drug, Rare Pediatric & Fast Track designations in pati
Slide 21: Pyruvate Kinase Deficiency (PKD): A Monogenic Red Blood Cell Hemolytic Disorder
Pyruvate Kinase Deficiency (PKD): A Monogenic Red Blood Cell Hemolytic Disorder RP-A501 RP-L301 RP-L102 RP-L201 Danon Disease Pyruvate Kinase Deficiency Fanconi Anemia Leukocyte Adhesion Deficiency-I MECHANISM OF ACTION: Current Available Treatments: Chronic blood transfusions and splenectomy—side e
Slide 22: RP-L301 (PKD): Phase 1 Overview of Clinical Study Design
RP-L301 (PKD): Phase 1 Overview of Clinical Study Design • Patients with prior splenectomy and severe Phase I Cohort Dosing Plan and/or transfusion-dependent anemia 1st cohort 2nd cohort 3rd cohort Adults (N=2) Adolescent (N=2) Pediatric (N=2) • Primary Endpoint: Safety and toxicity of RP-L301 ≥18 t
Slide 23: RP-L301 (PKD): Patients 1001 & 1002 Efficacy Results at 18 Months
RP-L301 (PKD): Patients 1001 & 1002 Efficacy Results at 18 Months Patient 1001 Patient 1002 Δ = 5.6 g/dL Δ = 7.2 g/dL • Marked hemoglobin improvement (~7.4 g/dL to 13.0 g/dL) • Hemoglobin normalized to 14.8 g/dL at ~18 months post- sustained at 18 months post-infusion infusion • No transfusion requi
Slide 24: RP-L301 (PKD) Conclusion: Sustained Safety and Efficacy in First 2 Patients
RP-L301 (PKD) Conclusion: Sustained Safety and Efficacy Observed in First 2 Patients at 1 Year • Safety profile of RP-L301 appears favorable with no IP-related SAEs • Insertion site analyses in PB and BM for both adult patients up to 12 months post-RP-L301 demonstrated highly polyclonal patterns and
Slide 25: RP-L301 (PKD): Development Plan
RP-L301 (PKD): Development Plan PKD Study Progress to Phase II and Launch ✓ Key Endpoints selected • Hgb increase • ↓50% transfusions or transfusion independence ✓ Well delineated natural history in recent PKD NHS publications ❑ Complete Phase I pediatric cohort dosing (N=2-3) ❑ End of Phase I Regul
Slide 26: Fanconi Anemia (FA): Monogenic DNA-repair disorder
Fanconi Anemia (FA): Monogenic DNA-repair disorder RP-A501 RP-L301 RP-L102 RP-L201 Danon Disease Pyruvate Kinase Deficiency Fanconi Anemia Leukocyte Adhesion Deficiency-I MECHANISM OF ACTION DNA Fanconi anemia complex Background: 80% of patients experience BMF double- strand B C DNA break A M repair
Slide 27: RP-L102 (FA): Clinical Program Overview
RP-L102 (FA): Clinical Program Overview RP-L102 Studies Non-randomized, open label studies: US Phase 1, US Phase 2, and EU Phase 2 (FANCOLEN-II) CMC/Drug Product “Process B” includes cell enrichment, transduction enhancers, commercial-grade vector and modified cell processing Clinical Studies ✓ EU F
Slide 28: RP-L102 (FA): Potential to Correct Bone Marrow Defect Without Conditioning
RP-L102 (FA): Potential to Correct Bone Marrow Defect Without Conditioning to Prevent Hematologic Failure Rationale for GTx in FA Based on Somatic Mosaicism Gene Therapy Value Proposition: • Small proportion of FA patients spontaneously revert to • Potential to correct blood & bone marrow defect nor
Slide 29: RP-L102 (FA): Highly Favorable Safety and Initial Efficacy Observed
RP-L102 (FA): Highly Favorable Safety and Initial Efficacy Observed Safety Data Efficacy Data Safety results appear highly favorable and RP- 12 patients received RP-L102 L102 well positioned as potential first-line treatment option* 6 of 9 show preliminary evidence of engraftment N = 9 with ≥ 12M fo
Slide 30: 12 Patients Treated: Demographics and Investigational Product Metrics
12 Patients Treated: Demographics and Investigational Product Metrics for Initial n=9 Mean VCN: CFC Age at Transduction Survival All patients ≤6 years at Enrollment Follow Up CD34+ Liquid Efficiency MMC enrollment Subject # (years) (months) Cells/kg CFCs/kg Culture CFCs (%) 10nM (%) 9 patients have
Slide 31: Sustained Genetic Correction in 6 of 9 Patients ≥1 year post-RP-L102
Sustained Genetic Correction in 6 of 9 Patients ≥1 year post-RP-L102 PBMC VCN BM VCN Progressive increases in gene markings in PB and BM in 6 patients Not shown: PB and BM VCN in Patient 2 (1002), who was withdrawn from the study at 18 months post-RP-L102 infusion 31
Slide 32: Increasing Phenotypic Correction over 1-2 years post-RP-L102
Increasing Phenotypic Correction over 1-2 years post-RP-L102 BM MMC-resistance * For 5 pts, increased BM CFC MMC resistance ranging from 51% to 94% observed at 18–24 months post-RP-L102 administration MMC resistance of >20% achieved at two consecutive timepoints ≥12 months for n=5 * BM MMC-res for p
Slide 33: BM CFC MMC Resistance is Associated with Long-term Hematologic Stability
BM CFC MMC Resistance is Associated with Long-term Hematologic Stability FANCOLEN-I (investigator-initiated) long-term follow-up: BM MMC-r leukocytes neutrophils hemoglobin platelets FA-2002 (246,000 cCD34+/Kg) Iron supplement FA-2006 (410,000 cCD34+/Kg) Months Post-Gene Therapy ≥20% BM CFC MMC resi
Slide 34: Genetic Correction Correlates with Phenotypic Improvement
Genetic Correction Correlates with Phenotypic Improvement - PB VCN strongly correlates with BM CFC MMC-Res at 12 months post-RP-L102 (r = 0.83)+* - BM Mononuclear cell VCN strongly correlates with BM CFC MMC-Res at 12 months post-RP-L102 (r = 0.81)** Patient 3 (2004) Patient 4 (2008) Patient 5 (2009
Slide 35: Increased BM CFC MMC Resistance Associated with Hematologic Stabilization
Increased BM CFC MMC Resistance Associated with Hematologic Stabilization at ≥1 year post RP-L102 Leukocytes Neutrophils Hemoglobin Platelets Patient 3 (2004) Patient 4 (2008) Concomitant blood count stabilization over 12–24 months seen in 5/5 Patient 5 (2009) patients with sustained and increasing
Slide 36: Conclusions from Initial 9 Patients with ≥1 Year of Follow-Up
Conclusions from Initial 9 Patients with ≥1 Year of Follow-Up Comprehensive efficacy in multiple patients with >1 year of follow-up • 5 patients have sustained, increasing BM CFC MMC resistance ranging from 51 to 94% at 18–24 months, and ≥20% at two consecutive timepoints • Increasing BM CFC MMC res
Slide 37: Leukocyte Adhesion Deficiency-I (LAD-I): A Monogenic Immunodeficiency
Leukocyte Adhesion Deficiency-I (LAD-I): A Monogenic Immunodeficiency RP-A501 RP-L301 RP-L102 RP-L201 Danon Disease Pyruvate Kinase Deficiency Fanconi Anemia Leukocyte Adhesion Deficiency-I MECHANISM OF ACTION Background: Autosomal recessive disease characterized by recurring ß2 Integrin and ultimat
Slide 38: Rationale for Gene Therapy in LAD-I: CD18 Expression Correlates to Patient Survival
Rationale for Gene Therapy in LAD-I: CD18 Expression Correlates to Patient Survival Kaplan-Meier Survival Estimates by Natural history studies show the Neutrophil CD18 Expression correlation between higher CD18 expression and longer patient survival, supporting gene therapy’s potential in LAD-I pati
Slide 39: RP-L201 Clinical Trial, Subject and Cell Product Characteristics
RP-L201 Clinical Trial, Subject and Cell Product Characteristics Trial Design Drug Age at • Non-Randomized Global Phase 1/2 Study (n=9) Patient Sex Product CD34+ Cell Dose enrollment VCN Key Eligibility Criteria • Severe LAD-I; CD18 expression <2% neutrophils, or CD11a/b <2% with L201-003-1001
Slide 40: RP-L201 (LAD-I): VCN in Peripheral Blood Mononuclear Cells (PBMCs)
RP-L201 (LAD-I): VCN in Peripheral Blood Mononuclear Cells (PBMCs) 4.0 L201-003-1001 Vector Copy Number L201-003-1004 3.0 L201-003-2006 L201-003-2005 2.0 L201-003-2007 L201-004-2008 1.0 L201-004-2009 L201-003-2011 0.0 L201-002-2010 Screening 0 3 6 9 12 15 18 21 24 Months Post-RP-L201 All 9 of 9 pati
Slide 41: RP-L201 (LAD-I): CD18 Expression in PB Polymorphonuclear Cells (PMNs)
RP-L201 (LAD-I): CD18 Expression in PB Polymorphonuclear Cells (PMNs) 100 L201-003-1001 %CD18+ PB PMNs 80 L201-003-1004 L201-003-2006 * 60 L201-003-2005 L201-003-2007 40 L201-004-2008 L201-004-2009 20 L201-003-2011 0 L201-002-2010 Screening 0 3 6 9 12 15 18 21 24 Months Post-RP-L201 All 9 of 9 patie
Slide 42: RP-L201 (LAD-I): Resolution of LAD-I Related Abnormal Leukocytosis
RP-L201 (LAD-I): Resolution of LAD-I Related Abnormal Leukocytosis A clinical biomarker of a normalized phenotype 28 Age at Leukocytes (×1000/μL) Enrollment 24 L201-003-1001 (9y) 20 L201-003-1004 (3y) * L201-003-2006 (7mo) 16 L201-003-2005 (3y) 12 L201-003-2007 (5mo) 8 L201-004-2008 (3y) L201-004-20
Slide 43: RP-L201 (LAD-I): Clinical Outcomes - Overall Survival & Incidence Reduction of Hospitalizations
RP-L201 (LAD-I): Clinical Outcomes - Overall Survival & Incidence Reduction of All Hospitalizations Overall Survival (OS) Kaplan-Meier Estimate Incidence of All Hospitalizations 1.0 Survival Probability 0.8 0.6 0.4 0.2 Censored 0.0 0 3 6 9 12 15 18 21 24 Months Post-RP-L201 Survival without • >2 yea
Slide 44: RP-L201 (LAD-I): Incidence Reduction of Infection and Inflammatory Related Hospitalizations
RP-L201 (LAD-I): Clinical Outcomes: Incidence Reduction of Infection and Inflammatory Related Hospitalizations, Prolonged Hospitalizations and Severe Infections Incidence of Infection and Inflammatory Incidence of Prolonged (>7 days) Incidence of Severe Infections Related Hospitalizations Hospitaliz
Slide 45: RP-L201 (LAD-I): Spontaneous Skin Rash Resolution and Restoration of Wound Repair
RP-L201 (LAD-I): Spontaneous LAD-I Related Skin Rash Resolution and Restoration of Wound Repair Capabilities after RP-L201 Spontaneous resolution of abdominal lesion Wound repair at thoracotomy site after surgical correction of double aortic arch L201-003-1001 L201-004-2008 3 months 6 months 12 mont
Slide 46: RP-L201 (LAD-I): Data Summary
RP-L201 (LAD-I): Data Summary • Phase 1/2 study enrollment complete: 9 of 9 severe LAD-I patients successfully treated • Safety profile of RP-L201 appears favorable: No drug product-related SAEs. Initial ISA indicates highly polyclonal patterns without evidence of dominant integrations in proximity
Slide 47: RP-L201 (LAD-I): Global Registrational Plan
RP-L201 (LAD-I): Global Registrational Plan ✓ Enrollment Completed; 9 of 9 patients treated Life-cycle Management ✓ Efficacy Seen in All 9/9 Patients with 3-24 months of Follow-Up ✓ Regulatory Designations: • Potential label expansion to include ➢ Fast Track and Advanced Therapy Medicinal Product (A
Slide 48: Replicating Core R&D Strategy for "Wave 2" Programs
Replicating Core R&D Strategy for “Wave 2” Programs We continue to build our pipeline based on our core R&D strategy; identify the “right” indications for the most efficient development path On Target Sizeable Market MOA; Clear to Maximize Endpoints Patient Impact First, Best and Only-in-class 48
Slide 49: Anticipated Program Milestones (2022 – 2024)
Anticipated Program Milestones (2022 – 2024) Our Path from Clinical to Commercial-Stage 2022 2023-2024 2Q 2022 3Q 2022 4Q 2022 • LAD-I & FA: Approvals & • LAD-I: Top line • FA: Top line data • Danon: Initiate Launches in U.S. & EU data Phase 2 pivotal • Danon: Pediatric • Wave 2 pipeline enters clin
Slide 50: Rocket Values & Partnerships
Rocket Values & Partnerships TRUST GENEROSITY CURIOSITY ELEVATE 50
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