Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — Investor Presentation (March 2021)
76 slides from Rocket Pharmaceuticals's investor presentation, March 2021
Slide 1: Corporate Presentation
Corporate Presentation March 2021 SEEKING GENE THERAPY CURES 1 NASDAQ: RCKT
Slide 2: Important Information
Important Information 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 2020 in light of COVID-19, the safety, effec
Slide 3: Mission, Vision and Values
Mission, Vision and Values TRUST GENEROSITY CURIOSITY ELEVATE Being generous means following Trust is given and trust is up, sharing our best ideas, The wonder of a child staring up Derived from Latin levis which earned – it’s a balance. The at the night sky. Humility, egoless- means “light” as oppo
Slide 4: Multi-Platform Gene Therapy Targeting Rare Diseases
Multi-Platform Gene Therapy Targeting Rare Diseases Clear and On Target Achievable Focused on MOA R&D Endpoints Strategy f for Sustainable Innovation First- and Best-in-class 4
Slide 5: Gene Therapy: A Multi-Platform Approach
Gene Therapy: A Multi-Platform Approach 5
Slide 6: About Rocket Pharma
About Rocket Pharma Multi-Platform Gene Therapy Multiple Near- & Medium- Strong Precedents and Company Targeting Rare Diseases: term Company Value Drivers World-Class Expertise 1st-in-class with direct on-target mechanism of action and clearly- defined clinical endpoints Near-term Milestones Strong
Slide 7: Rocket's Leadership Team
Rocket’s Leadership Team Gaurav Shah, M.D. Chief Executive Officer Spearheaded Kymriah (CART-19) development at Novartis towards approval Kinnari Patel, Pharm.D., MBA Claudine Prowse, Ph.D. President and Chief Operating Officer SVP, Strategy & Corporate Dev Led Opdivo and six rare disease indication
Slide 8: Rocket's Expanding Pipeline: Potential for Significant Value Creation
Rocket’s Expanding Pipeline: Potential for Significant Value Creation Near and Long Term DISCOVERY PRECLINICAL PHASE 1 PHASE 2 DESIGNATIONS Fast Track, Orphan RP-A501 Danon Disease Drug (U.S.), Rare AAV Pediatric Designation RMAT, ATMP, Fast Track, RP-L102 Fanconi Anemia Rare Pediatric, Orphan Drug
Slide 9: Fanconi Anemia (FA)
Fanconi Anemia (FA) Monogenic DNA-repair disorder RP-L102 RP-A501 RP-L201 RP-L301 RP-L401 Fanconi Anemia Danon Disease Leukocyte Adhesion Deficiency-I Pyruvate Kinase Deficiency Infantile Malignant Osteopetrosis OVERVIEW: Current available treatments: Allogeneic hematopoietic stem DNA double- Fancon
Slide 10: Potential to Correct Bone Marrow Defect without Conditioning
Potential to Correct Bone Marrow Defect without Conditioning to Prevent Hematologic Failure Rationale for GTx in FA: Gene Therapy Value Proposition: • Somatic mosaicism demonstrates that a modest • Potential to correct blood & bone marrow defect number of gene-corrected hematopoietic stem cells with
Slide 11: FA Path to Product Registration
FA Path to Product Registration CIEMAT-Sponsored • Interim data (>12-month follow-up) showed evidence of durable engraftment, continued FANCOLEN 1 Study improvement in phenotypic markers and stabilization of previously-declining blood counts Process A • No conditioning required O P T I M I Z AT I O
Slide 12: Bone Marrow Engraftment: Increasing Blood Cell VCNs
Bone Marrow Engraftment: Increasing Blood Cell VCNs Provide Evidence of Survival Advantage of Gene-Corrected FA Cells First Demonstration of Engraftment Without Conditioning (“Process A”—non-optimized—RP-L102) * 100 1 .0 0 * a r k e d ccells 30 0 .3 0 e lls e n e m a r k e d c e lls marked cells C o
Slide 13: Functional Correction of Bone Marrow
Functional Correction of Bone Marrow Progressive Phenotypic Correction of BM Cells (MMC-Resistance) Y = 0 .9 3 * X + 2 .6 3 R = 0 .8 3 80 100 e s is ta n c e (% ) r v i v a l (%) C r Resistance 60 C S uSurvival 10 40 M MMMC MMC MM 20 1 Months m o n th s P o s t-G T 0 6 12 24 36 0 6 12 24 0 6 12 24 3
Slide 14: Gene Therapy Confers a Phenotype Similar to Mosaicism
Gene Therapy Confers a Phenotype Similar to Mosaicism F A -0 2 0 0 2 FA-02002 FA-02006 F A -0 2 0 0 6 100 100 M e d ia n F A t c e lls 80 M e d ia n F A A b e r r a n cells A b e r r a n t cells c e lls 80 %%Aberrant 60 % Aberrant 60 40 40 20 % 20 0 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 0 3 6 9 12
Slide 15: Increases of Corrected Leukocytes Support Restoration of Bone Marrow Function
Increases of Corrected Leukocytes Support Restoration of Normal Bone Marrow Function Consistent with Mosaic Phenotype Kinetics of Corrected and Uncorrected PB Leukocytes Prior to and After Gene Therapy FA-02002 FA-02006 FA-02005 FA-02004 10000 10000 10000 10000 1000 1000 1000 Le u k o cy te s/ l Le
Slide 16: Gene Therapy Improves Previously Declining Blood Counts
Gene Therapy Improves Previously Declining Blood Counts in Optimally Treated Patients 300 4 16 N e u t r o pp hh ili lss ((xx11000000/ / l)l) 300 4 16 ( x11000000/ / l)l) 200 200 14 100 14 100 3 3 * ( g/ d/ dL L) ) 02002 (Cryo) 100 100 80 80 12 12 ts(x HHbb ( g 2.5x105 cCD34+/Kg PPl al at teel e
Slide 17: RP-L102 Process B: Pivotal Clinical Trials and Outcome Measures
RP-L102 “Process B”: Pivotal Clinical Trials and Outcome Measures 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 processi
Slide 18: RP-L102 Treated Study Patients
RP-L102 Treated Study Patients Age at • 9 patients treated across 3 Phase Patient # Site Gender Follow-up clinical sites, 2 under Phase 1 Enrollment and 7 under global Phase 2 PHASE 1 1 (1001) US 5 F 18M 2 (1002) US 6 F 18M • All patients ≤ 6-years at enrollment 3 (2004) Spain 3 M 12M • 3 patients h
Slide 19: RP-L102 Investigational Product Metrics
RP-L102 Investigational Product Metrics CFC Overall DP metrics Mean VCN: Mean Transductio were consistent with Follow- CD34+ Survival Phase Patient # CFCs/kg^ Liquid VCN: n Efficiency up Cells/kg^ MMC the more optimally Culture CFCs (%) 10nM (%) treated patients from FANCOLEN-I study 1 (1001) 18M 2.
Slide 20: RP-L102 Treated Study Patients (>12M Follow-up)
RP-L102 Treated Study Patients (>12M Follow-up) 1001 • Prior to gene therapy, decreases in multiple blood lineages over prior 12-24 months 2004 • Post gene therapy, stability across multiple blood lineages observed over 12-18 months 1002 • One patient with Influenza B infection 9-months post-rx; Req
Slide 21: RP-L102 Treated Study Patients (>12M Follow-up)
RP-L102 Treated Study Patients (>12M Follow-up) N = 3 with ≥ 12-Months of Follow-up • 2 of 3 showed increasing evidence of engraftment • 1 patient’s course (1002) complicated by Influenza B infection; received BMT • Of note: Additional 3 of 4 patients with 2-months follow-up have early evidence of e
Slide 22: RP-L102 Treated Study Patients (>12M Follow-up)
RP-L102 Treated Study Patients (>12M Follow-up) “Process B” BM VCN was in Line or Better than Optimally Treated “Process A” Patients at 12-Months Process B MMC Pending Process B MMC 31% Process A MMC 20% Process A MMC <10% Optimal means of the nine patients treated in Fancolen-I the two that had the
Slide 23: RP-L102 Treated Study Patients (>12M Follow-up)
RP-L102 Treated Study Patients (>12M Follow-up) Increasing Proportion of Gene-Corrected Cells Observed in Peripheral Blood Patient 1001 Patient 2004 FA: Patient 2004 FA: Patient 1001 10 10 FA: Patient 1001 10 Log10 WBC 1 Log10WBCS Log10 WBC 1 Log10WBCS Log10 WBC 1 0.1 0.1 0.1 0.01 0.01 -30 -20 -10 0
Slide 24: Summary of Pivotal RP-L102 Treated Study Patients
Summary of Pivotal RP-L102 Treated Study Patients PB VCN available for N = 7 5 of 7 showed preliminary evidence of engraftment N = 3 with ≥ 12M VCN N = 4 with early VCN (2M) • 2 of 3 showed increasing evidence of engraftment 3 showed early evidence of engraftment • 1 patient’s course (1002) complica
Slide 25: RP-L102 Conclusions: Optimized Process B
RP-L102 Conclusions: Optimized “Process B” Appears to be a Consistent and Reproducible Improvement over “Process A” • 9 out of 12 planned patients treated with “Process B” • 7 patients with follow-up data: 3 with ≥ 12M follow-up • Safety results appear highly favorable • Patients treated without con
Slide 26: Danon Disease
Danon Disease Monogenic Heart Failure Syndrome RP-L102 RP-A501 RP-L201 RP-L301 RP-L401 Fanconi Anemia Danon Disease Leukocyte Adhesion Deficiency-I Pyruvate Kinase Deficiency Infantile Malignant Osteopetrosis OVERVIEW: Background: Devastating multisystemic disorder caused by highly penetrant and X-l
Slide 27: An Impairment in Autophagy Caused by LAMP2B Mutations
An Impairment in Autophagy Caused by LAMP2B Mutations 27
Slide 28: Epidemiology and Market Opportunity
Epidemiology and Market Opportunity Hypertrophic Cardiomyopathy (HCM) • US HCM Prevalence: 600K-1MM+* • 1-4% of HCM patients consistently identified with LAMP2 mutations in multiple studies US + Europe with >1000 subjects evaluated** Prevalence: • Danon Disease Patients with HCM: *** ~15-30,000 o 85
Slide 29: Danon Disease Causes 1-4% of Hypertrophic Cardiomyopathy
Danon Disease Causes 1-4% of Hypertrophic Cardiomyopathy: Consistent Presence in Multiple Series Published 2004-Present Author & Age n HCM n Danon % Danon Note Year Charron Studied LAMP2 mutations in 197 HCM patients at a general hospital in N.A. 197 2 1.0% Paris 2004 Studied glycogen storage diseas
Slide 30: RP-A501 Restores Cardiac Function in KO Mice
RP-A501 Restores Cardiac Function in KO Mice Dose-Dependent Improvements in Systolic and Diastolic Function in LAMP2 KO Mice Cardiac Contractility Cardiac Relaxation Cardiac Contractility Cardiac Relaxation 10000 0 dP/dt min (mmHg/s) P<0.0001 dP/dt max (mmHg/s) P<0.0001 8000 P<0.0001 P<0.0001 -2000
Slide 31: RP-A501 Shows Survival Benefit at Higher Doses
RP-A501 Shows Survival Benefit at Higher Doses in Preclinical Studies Note: All mice were sacrificed at Month 10 31
Slide 32: RP-A501 Elicits Durable Expression of LAMP2B Protein
Protein: RP-A501 Elicits Durable Expression of LAMP2B Protein and Autophagy in Heart1 LAMP2 PROTEIN EXPRESSION LC3-II PROTEIN EXPRESSION WESTERN BLOT Mouse Human LAMP2 LAMP2 P = 0.0072 P = 0.019 1.5 (Normalized to GAPDH) 5 (Normalized to GAPDH) P = 0.033 LAMP2 Intensity 4 LC3-II Intensity P = 0.0001
Slide 33: RP-A501 Reduces Autophagic Vacuoles in All KO Mouse Models
Structural: RP-A501 Reduces Autophagic Vacuoles in All KO Mouse Models LAMP2 KO AAV9.LAMP2B Wild Type KO Control 5e13 vg/kg 1e14 vg/kg 2e14 vg/kg HEART LIVER S K E L E TA L MUSCLE 33
Slide 34: Dose-dependent LAMP2 Expression in Cardiac Tissue
Dose-dependent LAMP2 Expression in Cardiac Tissue 34
Slide 35: AAV9 Vector Shows Consistent Cardiac Tropism
AAV9 Vector Shows Consistent Cardiac Tropism in Several Studies Across Different Species DISORDER & VECTOR DOSE SPECIES RESULTS SPONSOR REFERENCE LGMD2A 8-80-fold higher transduction in cardiac vs. skeletal Lostal 3E+13 vg/kg NHP Genethon AAV9.hCAPN3 muscle (ASGCT 2018) Non-specific ~ 10-fold higher
Slide 36: Summary of Preclinical Data
Summary of Preclinical Data • Shows Phenotypic Improvements at Low-Dose • RP-A501 Preclinical Safety, Tox and 5e13 vg/kg: Biodistribution Summary: o Survival benefit at higher doses o No therapy-related deaths o Dose-dependent restoration of cardiac function o No significant hematologic changes o Im
Slide 37: RP-A501 Clinical Trial and Outcome Measures
RP-A501 Clinical Trial and Outcome Measures Study Design • Phase 1 open label study in male Danon patients Non- • Two age cohorts Randomized • Adolescent/Adult (>15 y) Dose-Escalation • Pediatric (8-14 y) Phase 1 Study • Treatment doses • Low 6.7 x 1013 GC/kg • Higher 1.1 x 1014 GC/kg1 Primary Outco
Slide 38: Natural History of Rapidly Progressing Heart Failure
Natural History of Rapidly Progressing Heart Failure Cardiac Clinical Features • Progressive hypertrophic cardiomyopathy/heart failure • Key Clinical Biomarker Changes o Echo: ⁃ Worsening diastolic parameters ⁃ ⇡ left ventricular end diastolic diameter (LVEDD) ⁃ ⇣ left ventricular fractional shorten
Slide 39: Female Danon Cardiac Histology Suggests Broad LAMP2 Expression
Female Danon Cardiac Histology Suggests Broad LAMP2 Expression Important for Reversal of Phenotype • Immunohistochemistry (IHC) from Danon female patients with severe disease display large patches negative for LAMP2 expression • Broad expression of LAMP2 is likely the key to correcting phenotype rat
Slide 40: RP-A501: Subject Characteristics & AAV Vector Dose
RP-A501: Subject Characteristics & AAV Vector Dose Age at Patient ID Dosing Weight Cohort Dose Total Dose Treatment 1001 17 y 52.2 kg 6.7 x 1013 GC/kg 3.25 x 1015 GC 1002 20 y 89.1 kg 6.7 x 1013 GC/kg 5.97 x 1015 GC 1005 18 y 97.8 kg 6.7 x 1013 GC/kg 6.08 x 1015 GC 1006 21 y 82.7 kg 1.1 x 1014 GC/kg
Slide 41: RP-A501 Demonstrated a Manageable Safety Profile
RP-A501 Demonstrated a Manageable Safety Profile • In Low-dose cohort, RP-A501 was generally well tolerated with manageable safety profile • Transient and reversible decline in platelets • Transient and reversible transaminase elevation • In Higher-dose cohort, a single patient experienced drug-rela
Slide 42: RP-A501 Low Dose: DNA Vector Copy Number
RP-A501 Low Dose: DNA Vector Copy Number 4 Pt 1001 Pt 1002 Pt 1005 Vector DNA copies per diploid genome 3.5 3 2.5 2 1.5 * 1 0.5 0 Baseline Long Term** * Clinical course and VCN drop suggest apparent poor compliance with steroid regimen ** 1001, 1002 Month 12; 1005 Month 9 42
Slide 43: RP-A501 Low Dose Cohort Demonstrates Robust Cardiac Expression
RP-A501 Low Dose Cohort Demonstrates Robust Cardiac Expression as Measured by LAMP2 Immunohistochemistry (IHC) LAMP2B Relative Expression vs. Control* Patient Regimen Week 8 Long Term Steroids only 1001 (limited compliance) 7.8% <15%*1 Steroids only 1002 36.9% 67.8%1 (local monitoring) 1005 Steroids
Slide 44: RP-A501 Low Dose: Robust Cardiac Expression of LAMP2 by IHC
RP-A501 Low Dose: Patients 1002 and 1005 Demonstrate Robust Cardiac Expression of LAMP2 by IHC Through Months 9 and 12, Respectively 1002 Month 12 Normal Heart Control 1002 Baseline 1005 Month 9 44 LAMP2 IHC (20x)
Slide 45: RP-A501 Low Dose: Endocardial LAMP2B Protein Expression
RP-A501 Low Dose: Endocardial LAMP2B Protein Expression Relative LAMP2B Expression vs. Normal By Western Blot Patient Week 8 Long Term 1001 20.7% 17.9%1 1002 27.3% - 1005 42.8% 61.1%2 1. Sample obtained at Month 6 2. Sample obtained at Month 9 45
Slide 46: RP-A501 Low Dose Improves or Stabilizes BNP
RP-A501 Low Dose Improves or Stabilizes Key Cardiac Marker of Heart Failure: B-type Natriuretic Peptide (BNP) 900 Pt 1001 800 Pt 1002 700 Pt 1005 BNP pg/ml 600 500 400 300 200 Normal BNP 100 0 BASE LIN E M ON T H 6 / 9 M ON T H 1 2 46
Slide 47: RP-A501 Electron Microscopy Shows Decrease in Vacuolar Pathology
RP-A501 Electron Microscopy of Cardiac Myocytes Demonstrates Marked Decrease in Vacuolar Pathology: Patient 1005 Baseline Week 8 Month 9 47
Slide 48: RP-A501 Low Dose Confers Improvement in Cardiac Output
RP-A501 Low Dose Confers Improvement in Cardiac Output Based on Invasive Hemodynamics in Patients 1002 and 1005 Cardiac Output (L/min) Patient Baseline Long Term1 1001 5.2 4.122 1002 3.58 5.82 (1.62x increase) 1005 4.5 6.083 (1.35x increase) 1. Calculated Stroke Volume: 40% increase in Patie
Slide 49: RP-A501 Low Dose: Safety & Efficacy Findings (n=3)
RP-A501 Low Dose: Safety & Efficacy Findings (n=3) • Generally, well tolerated with manageable safety profile in all low-dose patients • LAMP2B gene expression demonstrated in cardiac biopsies from all patients • Enhanced cardiac expression by IHC and Western blot in both patients whose compliance w
Slide 50: Leukocyte Adhesion Deficiency-I (LAD-I)
Leukocyte Adhesion Deficiency-I (LAD-I) Monogenic Immunodeficiency Disorder RP-L102 RP-A501 RP-L201 RP-L301 RP-L401 Fanconi Anemia Danon Disease Leukocyte Adhesion Deficiency-I Pyruvate Kinase Deficiency Infantile Malignant Osteopetrosis OVERVIEW: Background: Disorder characterized by recurring and
Slide 51: LAD-I Program Summary
LAD-I Program Summary Ultra-rare Disease = Streamlined Efficacy Trials & Registration Product/Manufacturing Regulatory Approach Status – Ahead of Schedule Optimization Potential design & clinical endpoints: Registration & study planning on- Process now optimized: schedule: • Target Patient Populatio
Slide 52: Rationale for Gene Therapy in LAD-I: CD18 Expression
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 53: LAD-I: Mouse Study Shows LAD-I Correction
LAD-I: Mouse Study Shows LAD-I Correction • Primary and serially transplanted LAD mice underwent CD18 lenti GTx with different promoters • Myeloablative conditioning was used • Rocket chose the Chimeric cFES/CTSG (myeloid-specific) promoter (Post- transplant PB VCN 0.4-0.9) Leon-Rico D, Aldea M, San
Slide 54: RP-L201 (LAD-I) Clinical Trial and Outcome Measures
RP-L201 (LAD-I) Clinical Trial and Outcome Measures1 Design • Enroll 9 pediatric patients globally Non- o Phase 1: Enroll two patients to assess safety and tolerability Randomized • Enrollment Complete o Phase 2: Overall survival at multiple sites (US and Europe) n=7 Phase 1/2 Study Primary Outcomes
Slide 55: Pre-Gene Therapy Medical History of Patient 1001
Pre-Gene Therapy Medical History of Patient 1001 Hospitalized Hospitalized IV Abx, Steroids IV Abx, Transfusion 9-y.o. female Suspected Nocardia Multiple Abscesses Hospitalized diagnosed with Buttocks Pneumonia IV Abx, Ustekinumab Severe Anemia severe LAD-I at Pyoderma Gangrenosum age 7 Enbrel, Abx
Slide 56: Patient 1001: 12-Month Follow-Up
Patient 1001: 12-Month Follow-Up Key Drug Product Metrics • CD34+ Cell Dose: 4.2 x 106 cells/kg • Drug Product VCN: 3.8 % CD18 Expression (PMN) VCN (PBMC) 36 PMN: polymorphonuclear lymphocytes PBMC: peripheral blood mononuclear cell 56
Slide 57: Patient 1001: Visible Improvements Post-Treatment
Patient 1001: Visible Improvements Post-Treatment Pre GTx: Severe infections ≥ 1 per year; numerous hospitalizations, severe skin lesions, continuous prophylactic antibiotics and required home schooling Post GTx: No infections or hospitalizations, off antibiotics and able to attend school Spontaneou
Slide 58: Pre-Treatment Medical History of Patient 1004
Pre-Treatment Medical History of Patient 1004 3-y.o. female Gingivitis/Periodontiis • Delayed umbilical cord separation • Diagnosed with LAD-I at age 3 Keflex Keflex • 2 younger siblings diagnosed LAD-I Recurrent Cellulitis Age Birth 1 2 3 (Years) 12/2015 12/2016 12/2017 12/2018 Hospitalized Dx with
Slide 59: Patient 1004: 6-Month Follow-Up
Patient 1004: 6-Month Follow-Up Key Drug Product Metrics • CD34+ Cell Dose: 2.8 x 106 cells/kg • Drug Product VCN: 2.5 % CD18 Expression (PMN) VCN (PBMC) CD18 at baseline was reported as dim in approximately 63% PMNs, likely indicating an unstable protein, and in the context of additional clinical a
Slide 60: Medical History & Follow-up of Patient 2006
Medical History & Follow-up of Patient 2006 7-m.o. male KEY DRUG PRODUCT METRICS • Diagnosed at birth given family history of disease • Delayed separation of umbilical cord (6 weeks) • 2 older siblings diagnosed with severe LAD-I CD34+ Cell Dose: Drug Product VCN: 4.3 x 106 cells/kg 2.87 Hospitalize
Slide 61: RP-L201 Study Summary
RP-L201 Study Summary • Drug product produced in 7 out of 9 patients in Ph 1 & Ph 2 • Safety results of RP-L201 appear favorable • Infusion well tolerated; no drug product-related SAEs or severe AEs as of November 2020 • Preliminary Efficacy of CD18 PMN expression observed in both patients with ≥ 6-
Slide 62: Pyruvate Kinase Deficiency (PKD)
Pyruvate Kinase Deficiency (PKD) Monogenic Red Blood Cell Hemolytic Disorder RP-L102 RP-A501 RP-L201 RP-L301 RP-L401 Fanconi Anemia Danon Disease Leukocyte Adhesion Deficiency-I Pyruvate Kinase Deficiency Infantile Malignant Osteopetrosis OVERVIEW: Current Available Treatments: Chronic blood transfu
Slide 63: Preclinical Studies Demonstrated Safety and Efficacy of Lentiviral Gene Therapy
Preclinical Studies Demonstrated Safety and Efficacy of Lentiviral- mediated Gene Therapy PKD mice transplanted with gene-corrected cells demonstrated phenotypic correction: • Significant increase in RBC count and half-life • Decreased erythropoietin levels • Normalized spleen and liver size & struc
Slide 64: RP-L301: Global Phase 1 PKD Gene Therapy Study
RP-L301: Global Phase 1 PKD Gene Therapy Study Primary Endpoint Key Eligibility Criteria Safety and toxicity of RP-L301 Inclusion: • PKD diagnosis with a confirmed PKLR mutation • Age: 1st cohort (N=2): ≥18 to 50-years Key Secondary Endpoints 2nd cohort (N=2): ≥12 to 17-years • Clinically significan
Slide 65: RP-L301: Patient Characteristics and Product Metrics
RP-L301: Patient Characteristics and Product Metrics Patient Characteristics Age (y) and Bilirubin Erythropoietin Transfusion Requirement for Patient Hemoglobin (g/dL) Gender (mg/dL) (mIU/mL) 2 Years Prior to Enrollment 1001 31 F 7.4† 13.4 mg/dL 35.6 mIU/mL ~14 transfusion episodes 1002* 47 M 7.0‡ 7
Slide 66: RP-L301: Preliminary Efficacy Results—L301-006-1001
RP-L301: Preliminary Efficacy Results—L301-006-1001 =6.9 g/dL * ➢ Marked hemoglobin improvement ~7.4 g/dL to 14.3 g/dL ➢ No transfusion requirements following engraftment * Lab Values during mobilization/apheresis & post-conditioning period were not included 66 Data as of October 2020
Slide 67: RP-L301: Preliminary Efficacy Results—Patient 1001
RP-L301: Preliminary Efficacy Results—Patient 1001 At 1–3 months post RP-L301 * --- Normal Range (2.59–18.5 mIU/mL) Reticulocytes decreased Erythropoietin normalized VCN in PBMCs 1.55 and VCN in BMMCs 2.72 at 3-months post RP-L301 Bilirubin decreased from Hepcidin increased from 13.4 mg/dL to 1.8 mg
Slide 68: RP-L301: Preliminary Safety Results
RP-L301: Preliminary Safety Results Treatment-emergent Adverse Events (Grade 3 or higher) (N=1 patient) ➤ No RP-L301 related adverse events Event Adverse Events Grade ➤ Patient 1001 achieved neutrophil System Organ Class (NCI CTCAE v. 5.0) Any 3 4 engraftment on day +13 Blood and lymphatic system di
Slide 69: RP-L301 Conclusion: Hemoglobin Normalized in First Patient
RP-L301 Conclusion: Hemoglobin Normalized in First Patient • Safety profile of RP-L301 appears favorable ◦ Infusion well tolerated (n=1); no IP-related SAEs or AEs ◦ Hematopoietic reconstitution in less than 2-weeks in initial patient • Preliminary efficacy activity observed during initial 3-months
Slide 70: Infantile Malignant Osteopetrosis (IMO)
Infantile Malignant Osteopetrosis (IMO) Monogenic bone resorption disorder RP-L102 RP-A501 RP-L201 RP-L301 RP-L401 Fanconi Anemia Danon Disease Leukocyte Adhesion Deficiency-I Pyruvate Kinase Deficiency Infantile Malignant Osteopetrosis OVERVIEW: Background: Dysfunctional osteoclast disease characte
Slide 71: Preclinical Mouse Data Supports Progression to Phase 1
Preclinical Mouse Data Supports Progression to Phase 1 Oc/oc mice receiving RP-L401 showed correction of the disease phenotype, with increased long-term survival, tooth eruption, weight gain, and normalized bone resorption Increased Long-term Survival Reversal of Osteopetrotic Bone Phenotype E-Poste
Slide 72: RP-L401 (IMO) Clinical Trial and Outcome Measures
RP-L401 (IMO) Clinical Trial and Outcome Measures1 Design Non- • Enroll 2 patients, with a confirmed diagnosis of IMO with documented TCIRG1 mutation Randomized o 1-month or older Phase 1 Study Primary Outcomes • Safety associated with treatment Secondary Outcomes • Normalization of serum calcium an
Slide 73: Growing IP Portfolio
Growing IP Portfolio Multiple in-licensed patent families for GTx products and related technology platforms Supporting current pipeline efforts: • Four In-licensed pending international patent applications filed under Patent Cooperation Treaty (PCT): o FA (2) o LAD-I o PKD • Multiple patent applicat
Slide 74: World-Class Research and Development Partners
World-Class Research and Development Partners CIBER IIS FJD REGENXBIO University of California, Los Angeles CIEMAT Lund University Stanford Medical School University of Minnesota Fred Hutchinson Cancer Memorial Sloan Kettering UCL University of Pennsylvania Research Center Cancer Center Hospital Uni
Slide 75: Expansion into Cranbury, NJ: R&D/CMC and cGMP Manufacturing
Expansion into Cranbury, NJ: R&D/CMC Efforts and Eventual cGMP Manufacturing 2021 • Continue R&D to further support CMC analytics and internal QC and release testing activities for RP-A501 • 50,000 sq. ft. from this facility will be dedicated to AAV cGMP manufacturing (FDA and EMA compliant) • Initi
Slide 76: Near and Long-Term Value Drivers
Near and Long-Term Value Drivers Potential for Five Gene Therapy Products to be Approved by 2025 2Q2021 2H2021 FA: Updated “Process B” Data PKD: Phase 1 Data Update LAD-I: Initial Phase 2 Data IMO: Initial Phase 1 Data Danon: Updated Phase 1 Data 76
Rocket Pharmaceuticals — Investor Presentation (March 2021) on 6ix