Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — 40th Annual J.P. Morgan Healthcare Conference (January 2022)
41 slides from Rocket Pharmaceuticals's conference presentation, Jan 10, 2022
Slide 1: 40th Annual J.P. Morgan Healthcare Conference: Rocket Pharmaceuticals Company Presentation
40th Annual J.P. Morgan Healthcare Conference Rocket Pharmaceuticals Company Presentation Gaurav Shah, MD Chief Executive Officer January 10, 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: RP-A501 (Danon Disease): Phase 1 Patients Treated to Date
RP-A501 (Danon Disease): Phase 1 Patients Treated to Date Non-Randomized Open Label Phase 1 Study (n= 7-9) Patient Age at Treatment Weight Primary Prophylactic Immunosuppression ID (years) (kg) Low Dose Adult 1001 17 52.2 Corticosteroids Age ≥15 years n=3 1002 20 89.1 Corticosteroids* 6.7
Slide 8: RP-A501 (Danon Disease): Current Program Safety & Efficacy Data
RP-A501 (Danon Disease): Current Program Safety & Efficacy Data • Safety data in initial pediatric patient suggests that modified immunosuppressive regimen has potential to mitigate AEs observed in Danon Disease Natural History adult low/high-dose cohorts o Sirolimus/Rituximab (+ steroid) → : Mini
Slide 9: RP-A501 (Danon Disease): Pediatric Patient (1008) Safety Data Summary
RP-A501 (Danon Disease): Pediatric Patient (1008) Safety Data Summary Post-implementation of enhanced risk-management plan • RP-A501 infusion was well tolerated • No drug-related SAEs • Mitigation of complement activation with stable platelets, Hgb and Cr • Baseline myopathy (Grade 1) remained stabl
Slide 10: RP-A501: Stabilization or Improvement of Cardiac Biomarkers and Functional Status
RP-A501: Stabilization or Improvement of Cardiac Biomarkers and Functional Status Across Dose Levels Most Recent Time of Cohort Patient ID Variable Baseline Follow-up Follow-up NYHA class II II 1001* BNP (pg/mL) 70 30 24 months 6 MWT (meters) 443 467 NYHA class II
Slide 11: RP-A501: Endomyocardial LAMP2B Protein Expression by IHC and Western Blot
RP-A501: Endomyocardial LAMP2B Protein Expression by Immunohistochemistry (IHC) and Western Blot LAMP2B Protein Expression LAMP2B Protein Expression (by IHC)** (by Western Blot) Cohort Patient ID Month 12 Month 5-18 2.5% 1001* 17.9%4 (Previously <15%)1 Adult – 1002 67.8% 21.2%5 Low Dose 1005 92.4%2
Slide 12: RP-A501 Low Dose: LAMP2 Protein Expression and Cell Morphology
RP-A501 Low Dose: LAMP2 Protein Expression by Immunohistochemistry and Cell Morphology by Electron Microscopy Normal Control Baseline Week 8 Month 9 Immunohistochemistry Represents LAMP2A, B & C Electron Microscopy Representative images from patient 1005 from biopsy of IVS 12
Slide 13: Danon Hypertrophic Cardiomyopathy Physiology and Endpoints
Danon Hypertrophic Cardiomyopathy Physiology and Endpoints ↑ LV posterior and septal Increased Wall Thickness wall thickness (Echo, cMRI) • ↑ Diastolic filling pressures o ↑ Pulmonary wedge pressure Decreased Diastolic (invasive hemodynamics at R heart cath) Relaxation • Preserved left ventricular e
Slide 14: RP-A501: Danon Patient's Heart Thickened on Echo
RP-A501: Danon Patient's Heart Thickened on Echo Normal Danon Patient 1002 Apical 4-Chamber View LVPWd PW IVS LV RV IVSd RA LA RA: right atrium LA: left atrium LVPWd: LVPW in diastole RV: right ventricle LV: left ventricle IVSd: IVS in diastole IVS: interventricular septum PW: posterior wall 14
Slide 15: RP-A501: Treated Patients Show Trend Toward Improvements in LV Wall Thickness
RP-A501: Treated Patients* Show Trend Toward Improvements in LV Wall Thickness vs. Untreated** Danon Males Untreated Danon Males RP-A501 Treated Patients LV Posterior Wall in diastole (LVPWd) [mm] n = 31 patients r = 0.709 Age [years] LV posterior wall thickens by 0.74 ± 0.12 mm/year in untreated Da
Slide 16: RP-A501: Treated Patients Show Trend Toward Improvements in Septal Wall Thickness
RP-A501: Treated Patients* Show Trend Toward Improvements in Septal Wall Thickness vs. Untreated** Danon Males Untreated Danon Males RP-A501 Treated Patients 1001 Septal Thickness Interventricular Septum in diastole (IVSd) n = 31 patients 1002 r= 0.741 40 1005 % Change from baseline 1006 Septum (End
Slide 17: Danon-related Increases in Left Ventricular Posterior Wall Corroborated by Longitudinal Echo
Danon-related Increases in Left Ventricular Posterior Wall Corroborated by Longitudinal Echo Results in Younger Patients * • Male Danon disease patients evaluated over median 3.1 years (range: ~ 2.4 – 12.2 years) • Age at initial evaluation median 8.6y (LVPWd) (range: ~ 5.7– 12.0 years) Echo Paramet
Slide 18: RP-A501: Gene Therapy Has Potential to Alter Natural History of Danon Disease
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 19: 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 20: 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 21: 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 22: RP-L301 (PKD): Patients 1001 & 1002 Efficacy Results at 1 Year
RP-L301 (PKD): Patients 1001 & 1002 Efficacy Results at 1 Year Patient 1001 Patient 1002 • Marked hemoglobin improvement (~7.4 g/dL to 13.3 g/dL) • Hemoglobin normalized to 14.8 g/dL at ~12 months post- sustained at 12 months post-infusion infusion • No transfusion requirements following engraftment
Slide 23: 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 • Preliminary efficacy sustained to date ◦ Normalized Hgb and improving hemolysis markers ◦ No red blood cell transfusion requirements
Slide 24: 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 25: 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 Background: 80% of patients experience BMF DNA Fanconi anemia complex double- strand B C DNA break A M within
Slide 26: 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 27: 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 28: 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- 11 patients received RP-L102 L102 well positioned as potential first-line treatment option* 7 of 9 show preliminary evidence of engraftment N = 8 with ≥ 12M fo
Slide 29: RP-L102 (FA): Treated Patients
RP-L102 (FA): Treated Patients Key Drug Product Characteristics Age at Phase Subject # Site Enrollment Gender Mean VCN: Follow-up CD34+ Cells/kg Liquid Culture 1 (1001) US 5 F 2.0 x 105 2.08 32M PH 1 2 (1002)* US 6 F 3.7 x 105 2.21 18M* 3 (2004) Spain 3 M 4.8 x 105 1.70 21M 4 (2008) Spain 2 F 3.2 x
Slide 30: RP-L102 (FA): Patients with ≥12M Follow-Up Demonstrate Genetic and Phenotypic Correction
RP-L102 (FA): Patients with ≥ 12M Follow-Up Demonstrate Evidence of Genetic and Phenotypic Correction Bone Marrow Patient BM CFC MMC Assessment Subject # Age at Resistance at 10 Performed Treatment nM MMC (%) (months) 1 (1001) 5 24 16† 3 (2004) 3 21 63 4 (2008) 2 12 21 5 (2009) 3 12 29 • Sustained P
Slide 31: RP-L102 (FA): Blood Count Stabilization in At Least 5 Patients
RP-L102 (FA): Blood Count Stabilization in At Least 5 Patients Subject 3 (2004) Subject 4 (2008) Subject 1 (1001) • Subject 1 (1001; BM CFC MMC Resistance 16%) had modest decline in blood counts with potential stabilization after ~18m; no transfusions have Subject 5 (2009) Subject 6 (2010) Subject 7
Slide 32: RP-L102 (FA): Path to Product Registration
RP-L102 (FA): Path to Product Registration Initial Efficacy and Highly Favorable Safety Profile: Additional Life-cycle Management Activities: Initial efficacy in 6 of 8 patients with >12M follow-up Expansion to FANC C & G No cytotoxic conditioning used, only one transient Exploration of non-
Slide 33: 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: Recurring and ultimately fatal infections caused by ß2 Integrin 1 ITGB2 gene
Slide 34: 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 Neutrophil CD18 Expression -Patients with moderate LAD-I not receiving allogeneic HSCT- Natural history studies show the correlation between higher CD18 expression and longer patien
Slide 35: RP-L201 (LAD-I): Subject and Cell Product Characteristics
RP-L201 (LAD-I): Subject and Cell Product Characteristics Age Patient ID Gender Drug Product VCN CD34+ Cell Dose (enrollment) 1 (1001) F 9 yrs. 3.8 4.2 x 106 cells/kg 2 (1004) F 3 yrs. 2.5 2.8 x 106 cells/kg 3 (2005) F 3 yrs. 1.8 6.5 x 106 cells/kg 4 (2006) M 7 mo. 2.9 4.3 x 106 c
Slide 36: RP-L201 (LAD-I): CD18 & VCN Expression in PB Neutrophils
RP-L201 (LAD-I): CD18 & VCN Expression in PB Neutrophils * CD18 > 10% *Dim/weak CD18 expression reported at baseline for PT 1004 in ~60% of Cells All 9 of 9 patients with CD18 > 10% LAD has received CIRM Funding. Data as of December 2021 36
Slide 37: RP-L201 (LAD-I): Data Summary
RP-L201 (LAD-I): Data Summary • Phase 1/2 study complete: 9 of 9 severe LAD-I patients successfully treated • Safety profile of RP-L201 appears favorable: o No drug product-related SAEs • Efficacy evident in all 9 severe LAD-I patients with follow-up of 3-24m o Includes 4 patients with ≥ 12-months o
Slide 38: RP-L201 (LAD-I): Global Registrational Plan
RP-L201 (LAD-I): Global Registrational Plan Enrollment Completed; 9 of 9 patients dosed Life-cycle Management Efficacy Seen in All 9 Patients with Minimum 3 Months Follow- Up • Potential label expansion to include Regulatory Designations: moderate LAD-I population Fast Track and Advanced The
Slide 39: 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 39
Slide 40: 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 41: Rocket Values & Partnerships
Rocket Values & Partnerships TRUST GENEROSITY CURIOSITY ELEVATE Stanford Medical School 41
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