Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — Investor Presentation (December 2021)
84 slides from Rocket Pharmaceuticals's investor presentation, December 2021
Slide 1: Corporate Presentation
Corporate Presentation December 2021 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 2021 in light of COVID-19, the safety, effectiveness and timing of
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 forgiving ourselves and others, at the night sky. Humility
Slide 4: Multi-Platform Gene Therapy Targeting Rare Diseases
Multi-Platform Gene Therapy Targeting Rare Diseases Clear and On Target Achievable Focused on MOA Endpoints R&D 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 Jonathan Schwartz, M.D. President and Chief Operating Officer CMO & Clinical Development, SVP Led Opdivo and six rare disease indicat
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: 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 13: RP-L102 Treated Study Patients
RP-L102 Treated Study Patients Age at • 11 subjects treated across 3 Phase Subject # Site Gender Follow-up Enrollment clinical sites, 2 under US Phase 1 (1001) US 5 F 32M PHASE 1 1 and 9 under global Phase 2 2 (1002)* US 6 F 18M* • All subjects ≤6 years at 3 (2004) Spain 3 M 21M enrollment 4 (2008)
Slide 14: RP-L102 Investigational Product Metrics
RP-L102 Investigational Product Metrics Mean VCN: Transduction CFC Survival Overall DP metrics CD34+ Mean VCN: Phase Subject # CFCs/kg Liquid Efficiency MMC are consistent with Cells/kg CFCs Culture (%) 10nM (%) the more optimally 1 (1001)* 2.0 x 105 5.2 x 104 2.08 0.62 67 33 treated subjects PHASE
Slide 15: RP-L102 Study Patients with ≥12m Follow Up Demonstrate Genetic and Phenotypic Correction
RP-L102 Study 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 PB
Slide 16: Blood Count Stabilization in Patients with BM CFC MMC Resistance ≥10%
Blood Count Stabilization in at Least 5 Patients with BM CFC MMC Resistance ≥10% Subject 3 (2004) Subject 4 (2008) Subject 1 (1001) • Blood count stabilization in 5/5 patients with BM CFC MMC Resistance ≥ 20% • Patient 1 (1001; MMC-res 16%) had modest decline in blood Subject 5 (2009) Subject 6 (201
Slide 17: Summary of Pivotal RP-L102 Treated Study Patients
Summary of Pivotal RP-L102 Treated Study Patients 11 Patients have received RP-L102 7 of 9 showed preliminary evidence of engraftment N = 8 with ≥ 12M Follow-up (12-32M) • 6 of 8 showed increasing evidence of engraftment with increase in MMC resistance ranging from 16-63% N = 3 with < 12 months of f
Slide 18: RP-L102 Conclusions: Optimized Process B
RP-L102 Conclusions: Optimized “Process B” Appears to be a Consistent and Reproducible Improvement over “Process A” • 11 patients treated with “Process B” • Safety results appear highly favorable • Patients treated without conditioning • No signs of dysplasia or other concerning features • RP-L102 r
Slide 19: 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 20: An Impairment in Autophagy Caused by LAMP2B Mutations
An Impairment in Autophagy Caused by LAMP2B Mutations 20
Slide 21: 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 22: 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 23: 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 P<0.0001 P<0.0001 P<0.0001 P<0.0001 P=0.045 P=0.011 P=0.005 P=0.0093 P=0.0018 P=0.005 * * Lower dP/dt max indicates impaired contracti
Slide 24: RP-A501 Shows Survival Benefit at Higher Doses in Preclinical Studies
RP-A501 Shows Survival Benefit at Higher Doses in Preclinical Studies Note: All mice were sacrificed at Month 10 24
Slide 25: RP-A501 Elicits Durable Expression of LAMP2B Protein and Autophagy in Heart
Protein: RP-A501 Elicits Durable Expression of LAMP2B Protein and Autophagy in Heart1 LAMP2 PROTEIN EXPRESSION LC3-II PROTEIN EXPRESSION WESTERN BLOT 1Data are Mean ± SEM. N=5-8 per group. Untx = Untreated, PBS = Phosphate buffered saline Note: Mouse LAMP2 and Human LAMP2 data are from separate West
Slide 26: 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 26
Slide 27: Dose-dependent LAMP2 Expression in Cardiac Tissue
Dose-dependent LAMP2 Expression in Cardiac Tissue 27
Slide 28: AAV9 Vector Shows Consistent Cardiac Tropism Across Species
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 29: 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 30: 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/kg (removed going
Slide 31: 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 32: 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 33: RP-A501: Patient Entry Criteria
RP-A501: Patient Entry Criteria Inclusion Exclusion • Male • Anti-AAV9 neutralizing antibody titer criteria • Confirmed LAMP2B mutation • LVEF <40% at baseline • Cardiac involvement confirmed by echocardiogram, • Acute or chronic respiratory failure on MRI or ECG ventilatory support • NYHA Class II
Slide 34: RP-A501: Baseline Clinical Status and Biomarker Values
RP-A501: Baseline Clinical Status and Biomarker Values Clinical Status Biomarker Cohort Patient ID Age at Enrollment Weight (kg) NYHA Six Minute Walk BNP Class (meters) [<100 pg/mL] 17 1001 52.2 II 443 70 years 20 Adult - Low Dose 1002 89.1 II 405 1104 years 18 1005 91.8 II 427 16
Slide 35: RP-A501: Baseline Patient Status
RP-A501: Baseline Patient Status Echocardiogram Catheterization Hypertrophic Cardiomyopathy Patient Age at Weight Cohort Wall ID Enrollment (kg) LV EF** PCWp Thickness* 1. Thickened myocardium [50-75%] [8-12 mmHg] [6-11 mm] • LV posterior wall • Interventricular septum 17 1001 52.2 16.4 62 11 ye
Slide 36: RP-A501: High Dose Summary of Safety and Tolerability
RP-A501: High Dose Summary of Safety and Tolerability Immediate: n Early: n Delayed: n High Dose Adult n=2* Fever 1 Complement activation 1** Transaminase elevation 1 and Adolescent Fatigue 2 Thrombocytopenia 2 Deep vein thrombosis 1 Age ≥15 years Constipation 1 Transaminase elevation 2 Steroid-indu
Slide 37: RP-A501: Low Dose Summary of Safety and Tolerability
RP-A501: Low Dose Summary of Safety and Tolerability Low Dose Adult Immediate: n Early: n Delayed: n and Adolescent n=3 Fever 1 Complement activation 2* Transaminase elevation 2 Fatigue 1 Thrombocytopenia 2 Steroid-induced myopathy 2 Age ≥15 years Constipation 2 Transaminase elevation 3 Salmonella S
Slide 38: 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 Cohort Patient ID Variable Baseline Most Recent Follow-up Time of Follow-up NYHA class II II 1001* BNP (pg/mL) 70 30 24 months 6 MWT (meters) 443 467 NYHA class II
Slide 39: RP-A501 Adolescent and Adult: Echocardiogram (Apical 4-Chamber View)
RP-A501 Adolescent and Adult: Echocardiogram (Apical 4-Chamber View) Normal Danon Patient 1002 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 39 CONFID
Slide 40: Danon Natural History: LV Posterior & Septal Wall Thickness (Echo)
Danon Natural History: LV Posterior & Septal Wall Thickness (Echo) Interventricular Septum in diastole (IVSd) [mm] LV Posterior Wall in diastole (LVPWd) [mm] Age [years] Age [years] Retrospective Review of Echocardiograph Data from N=32 Male Danon Patients 40
Slide 41: Remodeling of Ventricular Hypertrophy on Echocardiography
Remodeling of Ventricular Hypertrophy on Echocardiography (LVPWd) (IVSd) LVPW IVS All echocardiographic parameters from local laboratory assessment, conducted by a single reader 41 CONFIDENTIAL & PROPRIETARY
Slide 42: Stabilization or Improvement of LV EF and Wall Thickness
Stabilization or Improvement of LV EF and Wall Thickness All echocardiographic parameters from local laboratory assessment, conducted by a single reader 42 CONFIDENTIAL & PROPRIETARY
Slide 43: Invasive Hemodynamics Demonstrated Long Term Stabilization of Diastolic Dysfunction
Invasive Hemodynamics Demonstrated Long Term Stabilization or Improvement of Diastolic Dysfunction (LV Filling Pressure) 43
Slide 44: Hemodynamic Stabilization of Systolic Function
Hemodynamic Stabilization of Systolic Function Cardiac Output = Stroke Volume x Heart Rate 44
Slide 45: RP-A501 Demonstrated Stable Cardiac Vector Copy Numbers (VCN)
RP-A501 Demonstrated Stable Cardiac Vector Copy Numbers (VCN) Cardiac VCN Cohort Patient ID Week 8 Month 12 1001* 0.5 0.6 Adult - Low Dose 1002 6.5 1.5 1005 2.5 1.91 1006 3.9 1.1 Adult - High Dose 6.8 (RV)2 1007 5.9 9.2 (LV)2 1 Month 9 data 2 Explanted heart samples at Month 5 * Patient 1001 was onl
Slide 46: Endomyocardial LAMP2B Protein Expression by Immunohistochemistry (IHC)
Endomyocardial LAMP2B Protein Expression by Immunohistochemistry (IHC) LAMP2B Protein Expression (by IHC)** Cohort Patient ID Week 8 Month 12 7.3% 2.5% 1001* (Previously <15%)1 Adult - Low Dose 1002 36.9% 67.8% 1005 17.6% 92.4%2 1006 5.0% 100% Adult - High Dose 1007 6.9% 100%3 1 Previously disclosed
Slide 47: Endomyocardial LAMP2B Western Blot Protein Expression
Endomyocardial LAMP2B Western Blot Protein Expression LAMP2B Protein Expression Cohort Patient ID (by Western Blot) Week 8 Month 5-18 1001 20.7% 17.9%1 Adult - Low Dose 1002 27.3% 21.2%2 1005 42.8% 61.1%3 1006 14.6% 18.2%1 Adult – High Dose RV: 45.1%4 1007 25.0% LV: 44.0%4 1 Month 6 data; inadequate
Slide 48: RP-A501 Low Dose: LAMP2 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 Electron Microscopy Representative images from patient 1005 from biopsy of IVS 48
Slide 49: RP-A501 High Dose: LAMP2 Expression and Cell Morphology
RP-A501 High Dose: LAMP2 Protein Expression by Immunohistochemistry and Cell Morphology by Electron Microscopy Normal Control Baseline Week 8 Month 12 Immunohistochemistry Electron Microscopy Representative images from patient 1006 from biopsy of IVS 49
Slide 50: RP-A501: Stable or Improved Clinical Biomarkers
RP-A501: Stable or Improved Clinical Biomarkers 50
Slide 51: RP-A501 High Dose: Patient 1007 Danon Disease Progression
RP-A501 High Dose: Patient 1007 Danon Disease Progression 20 Year-old Male Danon Patient • Baseline risk factors suggest "point of no return" in Danon disease progression • Diminished LV EF (35%) • Markedly elevated LV filling pressure (PCWp 26 mmHg) • Prior evidence of fibrosis on MRI • Continued c
Slide 52: Patient 1007 Predose and Explanted Heart Myocardial Tissue
Patient 1007 Predose and Explanted Heart Myocardial Tissue* Pre-Dose Biopsy (IVS) Week 8 Biopsy (IVS) Explanted Heart – 5M post treatment RV LV LAMP2B Protein Expression (by IHC) Patient ID Month 5 Month 5 Week 8 Explant RV Explant LV 1007 6.8% 100% 100% * Atrial VCN and LAMP2 expression was consist
Slide 53: RP-A501 High Dose Adult and Adolescent Cohort Summary (N=2)
RP-A501 High Dose Adult and Adolescent Cohort Summary (N=2) • RP-A501 r-AAV dose-dependent toxicity was seen at 1.1x1014 GC/kg dose levels • One of two patients developed thrombotic microangiopathy (TMA) • Acute renal failure managed with hemodialysis and eculizumab • Baseline LV systolic failure ma
Slide 54: RP-A501 Low Dose Adult and Adolescent Cohort Summary (N=3)
RP-A501 Low Dose Adult and Adolescent Cohort Summary (N=3) RP-A501 r-AAV generally well tolerated at 6.7x1013 GC/kg dose level • Tailored immunosuppressive regimen • Reversible immunologic response with no lasting clinical sequelae Clinical parameters improved or remained stable • Functional and Bio
Slide 55: 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 56: 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 57: Rationale for Gene Therapy in LAD-I: CD18 Expression Correlates to 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 58: 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 59: 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 o Phase 2: Overall survival at multiple sites (US and Europe) n=7 Phase 1/2 Primary Outcomes Study • Phase 1: o Safety a
Slide 60: RP-L201: Subject and Cell Product Characteristics
RP-L201: 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 cells/kg
Slide 61: RP-L201: CD18 Expression in PB Neutrophils
RP-L201: CD18 Expression in PB Neutrophils * *Dim/weak CD18 expression reported at baseline for PT 1004 in ~60% of Cells LAD has received CIRM Funding. Data as of December 2021 61
Slide 62: RP-L201: VCN in PBMCs
RP-L201: VCN in PBMCs PBMC: peripheral blood mononuclear cell LAD has received CIRM Funding. Data as of December 2021. 62
Slide 63: RP-L201: Improvements in Leukocytosis Seen Across Patients
RP-L201: Improvements in Leukocytosis Seen Across Patients White Blood Cell Counts in Peripheral Blood LAD has received CIRM Funding. Data as of December 2021. 63
Slide 64: 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 diagnosed with Pneumonia Hospitalized Buttocks IV Abx, Ustekinumab Severe Anemia severe LAD-I at Pyoderma Gangrenosum age 7 Enbrel, Abx
Slide 65: 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 66: 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 67: Pre-Treatment Medical History of Patient 2005
Pre-Treatment Medical History of Patient 2005 2-y.o. female at enrollment • Diagnosed with LAD-I at age 2 • 2 older siblings diagnosed with severe LAD-I Hospitalized Treated Oral Ulcers Age Birth 6M 1Y 18M 2Y (Years) 5/2017 11/2017 5/2018 11/2018 5/2019 Impetigo Otitis Abx Enrolled Media Pressure Eq
Slide 68: Pre-Treatment Medical History of Patient 2006
Pre-Treatment Medical History of Patient 2006 7-m.o. male • Diagnosed at birth given family history of disease • Delayed separation of umbilical cord (6 weeks) • 2 older siblings diagnosed with severe LAD-I Hospitalized Age Human metapneumovirus 1 Birth (Years) 10/2019 10/2019 Dx with LAD-I Hospital
Slide 69: RP-L201 Study Summary
RP-L201 Study Summary • Enrollment and dosing complete: 9 of 9 severe LAD-1 patients successfully dosed with RP-L201 • Safety profile of RP-L201 appears favorable: • Infusion well tolerated; no drug product-related SAEs or severe Aes • Neutrophil engraftment achieved in all subjects in <34 days post
Slide 70: 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 71: Preclinical Studies Demonstrated Safety and Efficacy of Lentiviral-mediated 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 72: 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 73: 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 74: RP-L301: Preliminary Efficacy Results—Patient 1001
RP-L301: Preliminary Efficacy Results—Patient 1001 =5.9 g/dL ~20 pRBC units transfused over 30m period Transfusion independence Marked hemoglobin improvement ~7.4 g/dL to 13.3 g/dL (sustained at 12 months post-infusion) No transfusion requirements following engraftment Note: Lab Values during m
Slide 75: RP-L301: Preliminary Efficacy Results—Patient 1001
RP-L301: Preliminary Efficacy Results—Patient 1001 At 1-12 months post RP-L301 --- Normal Range --- Normal Range (2.59–18.5 mIU/mL) (0.5–1.5%) * Sustained reduction in Erythropoietin normalized reticulocytes --- Normal Range (0.3–1.2 mg/dL) --- Normal Range (0.4–47.3 ng/mL) Stable VCN in PBMCs of 1.
Slide 76: RP-L301: Preliminary Efficacy Results—Patient 1002
RP-L301: Preliminary Efficacy Results—Patient 1002 = 7.2 g/dL ~7 transfusion events over 50m period Transfusion independence Hemoglobin normalized to 14.8 g/dL at ~12 months post-rx No red blood cell transfusion requirements following engraftment Note: Lab Values during mobilization/apheresis &
Slide 77: RP-L301: Preliminary Efficacy Results—Patient 1002
RP-L301: Preliminary Efficacy Results—Patient 1002 At 1-12 months post RP-L301 --- Normal Range --- Normal Range (0.45–2.28%) (2.6–18.5 mIU/mL) Significant improvement in Significant decrease in reticulocytes from 25.5% to 2.73% erythropoietin levels --- Normal Range (0–1.4 mg/dL) --- Normal Range (
Slide 78: RP-L301 Conclusion: Sustained Efficacy in First 2 Patients at 1 Year
RP-L301 Conclusion: Sustained Efficacy in First 2 Patients at 1 Year • Safety profile of RP-L301 appears favorable ◦ Infusion well tolerated in (N=2); no IP-related serious adverse events (SAEs) through 12-months post- infusion in adult patients ◦ Hematopoietic reconstitution in less than 2 weeks ◦
Slide 79: 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 80: 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 81: 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 Study2 Primary Outcomes • Safety associated with treatment Secondary Outcomes • Normalization of serum calcium a
Slide 82: 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 83: 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 84: Expansion into Cranbury, NJ: R&D/CMC Efforts and Eventual 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) • In-ho
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