Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — Investor Presentation (November 2021)
85 slides from Rocket Pharmaceuticals's investor presentation, November 2021
Slide 1: Corporate Presentation
Corporate Presentation November 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 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 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 Phase Subject # Site Age at Gender Follow-up • 9 subjects treated across 3 Enrollment clinical sites, 2 under US Phase PHASE 1 1 (1001) US 5 F 24M 1 and 7 under global Phase 2 2 (1002)* US 6 F 18M • All subjects ≤6 years at enrollment 3 (2004) Spain 3 M 15M • 6 subject
Slide 14: RP-L102 Investigational Product Metrics
RP-L102 Investigational Product Metrics Transduction CFC Survival Overall DP metrics CD34+ Mean VCN: Mean VCN: Phase Subject # CFCs/kg Efficiency MMC are consistent with Cells/kg Liquid Culture CFCs (%) 10nM (%) the more optimally treated subjects PHASE 1 1 (1001)* 2.0 x 105 5.2 x 104 2.08 0.62 67 3
Slide 15: RP-L102 Treated Study Patients (>12M Follow-up)
RP-L102 Treated Study Patients (>12M Follow-up) Vector Copy Number in: Subject 1 (1001) Subject 3 (2004) Increasing BM progenitor resistance to 10 nM MMC seen in both subjects • Subject 1: 16% at 2 years* post-RP-L102 infusion • Subject 3: 29% at 1 year post-RP-L102 infusion • Sustained increasing V
Slide 16: RP-L102 Study Subjects with ≥6 mo Follow Up
RP-L102 Study Subjects with ≥6 mo Follow Up Subject 4 (2008) Subject 5 (2009) Subject 6 (2010)* Subject 7 (2011)* At 6 months post-RP-L102 treatment, Subjects 4 and 5 have early evidence of BM progenitor resistance (25% and 14% respectively) to 10 nM MMC, consistent with BMMC VCN; All subjects have
Slide 17: Summary of Pivotal RP-L102 Treated Study Patients
Summary of Pivotal RP-L102 Treated Study Patients PB VCN available for N = 9 7 of 9 showed preliminary evidence of engraftment N = 6 with ≥ 6M VCN • 6 of 7 showed increasing evidence of engraftment N = 1 with early VCN • 1 patient’s course (1002) complicated by Influenza B showed detectable VCN at e
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” • 9 patients treated with “Process B” • Safety results appear highly favorable • Patients treated without conditioning • No signs of dysplasia or other concerning features • RP-L102 re
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 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 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
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 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
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
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
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 1001 Posterior Wall Thickness 1001 Septum Thickness 1002 (LVPWd) 1002 (IVSd) Posterior Wall (End-Diastole) 40 40 1005 % Change from baseline % Change from baseline 1005 Septum (End-Diastole) 1006 20 1006 20 Stabilization Stabilization 0 0 Imp
Slide 42: Stabilization or Improvement of LV EF and Wall Thickness
Stabilization or Improvement of LV EF and Wall Thickness Posterior Wall Patient 1001 Posterior Wall %Ejection Fraction Patient 1002 %Ejection Fraction 30 80 30 80 Ejection Fraction, % (End-Diastole), mm Ejection Fraction, % (End-Diastole), mm Posterior Wall 60 Posterior Wall 20 60 20 40 40 10 20 10
Slide 43: Invasive Hemodynamics Demonstrated Long Term Stabilization
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 1001 100 8 Stroke Volume (mL/beat) Normal SV 1002 Normal CO Cardiac Output, L/min 80 1005 6 1006 60 4 40 2 20 0 0 Baseline M2 M6 M9 M12 M18 Baseline M2 M6 M9 M12 M18 Months post gene therapy Months post gene therapy Cardiac
Slide 45: RP-A501 Demonstrated Stable Cardiac Vector Copy Numbers
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 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 Creatinine Kinase 1001 300 1002 %Change from Baseline 1005 Creatinine Kinase 200 1006 100 Stabilization 0 Improvement -100 Baseline M6 M12 M18 M24 Months post gene therapy Aspartate Transaminase 1001 Alanine Transaminase 1001 300 1002 300 1002 %Change
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 Vector DNA Copies/diploid genome (VCN) Patient 1007 Heart VCN 10 0.00 9.15 8 LAMP2B Protein Expression (by IHC) 6.77 6 5.85 Patient ID Month 5 Month 5 4 Wee
Slide 53: RP-A501 High Dose Adult and Adolescent Cohort Summary
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
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 and 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) 1001 F 9 yrs. 3.8 4.2 x 106 /kg 1004 F 3 yrs. 2.5 2.8 x 106 /kg 2005 F 2 yrs. 1.8 6.5 x 106 /kg 2006 M 7 mo. 2.9 4.3 x 106 /kg 2007 M 3y 3.6 5.0 x 106 /kg 2008 M 5m 3.8 3.3 x 106 /kg
Slide 61: RP-L201: CD18 Expression in PB Neutrophils
RP-L201: CD18 Expression in PB Neutrophils *Shipping delays (due to COVID pandemic) may cause under-representation of results **Dim/weak CD18 expression reported at baseline for PT 1004 in ~60% of Cells * * * ** Data as of September 2021 LAD has received CIRM Funding 61
Slide 62: RP-L201: VCN in PBMCs
RP-L201: VCN in PBMCs PBMC: peripheral blood mononuclear cell Data as of September 2021 LAD has received CIRM Funding 62
Slide 63: RP-L201: Hematopoietic Recovery in Initial Patients
RP-L201: Hematopoietic Recovery in Initial 2 Patients 300 200 100 x103/µl PLAT(103/µl) 1001 20 PLAT(103/µl) 1004 15 NEUT(103/µl) 1001 NEUT(103/µl) 1004 10 5 0 0 20 40 60 Days post gene therapy Data as of September 2021 LAD has received CIRM Funding 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 Hospitalized diagnosed with Buttocks Pneumonia 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 • Seven severe LAD-I patients have been successfully infused with RP-L201 with at least 3-months of follow-up • Safety profile of RP-L201 appears favorable: • Infusion well tolerated; no drug product-related SAEs or severe Aes • Neutrophil engraftment achieved in all subjects i
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 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 =6.5 g/dL * ➢ Marked hemoglobin improvement ~7.4 g/dL to 13.9 g/dL (over 9 months post-infusion) ➢ No transfusion requirements following engraftment * Lab Values during mobilization/apheresis & post-conditioning period were not included 74 Data as
Slide 75: RP-L301: Preliminary Efficacy Results—Patient 1001
RP-L301: Preliminary Efficacy Results—Patient 1001 At 1–9 months post RP-L301 * --- Normal Range (2.59–18.5 mIU/mL) Sustained reduction in Erythropoietin normalized reticulocytes Stable VCN in PBMCs of 1.67 at 9 months and VCN in BMMCs 2.72 at 3 months post RP-L301 Bilirubin decreased from Hepcidin
Slide 76: RP-L301: Preliminary Efficacy Results—Patient 1002
RP-L301: Preliminary Efficacy Results—Patient 1002 =6.8 g/dL * ➢ Hemoglobin normalized to 14.4 g/dL at ~6 months post-rx ➢ No red blood cell transfusion requirements following engraftment * Lab Values during mobilization/apheresis & post-conditioning period were not included 76 Data as of May 2021
Slide 77: RP-L301: Preliminary Efficacy Results—Patient 1002
RP-L301: Preliminary Efficacy Results—Patient 1002 At 1–6 months post RP-L301 * --- Normal Range (2.6–18.5 mIU/mL) Significant improvement in Erythropoietin normalized reticulocytes from 25.5% to 3.9% --- Normal Range (35–278 mg/dL) <30 mg/dL Stable PBMC VCN of 2.55 and BMMC VCN of 2.88 at 3 months
Slide 78: RP-L301 Conclusion: Hemoglobin Normalized in First Patients
RP-L301 Conclusion: Hemoglobin Normalized in First 2 Patients • Safety profile of RP-L301 appears favorable ◦ Infusion well tolerated in (N=2); no IP-related serious adverse events (SAEs) at 9- and 6- months post- infusion in adult patients ◦ Hematopoietic reconstitution in less than 2 weeks ◦ Patie
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 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) • In-ho
Slide 85: Anticipated Program Milestones
Anticipated Program Milestones Potential for Five Gene Therapy Products to be Approved by 2025 Milestones Anticipated in 4Q 2021 RP-L102 RP-A501 RP-L201 RP-L301 RP-L401 Leukocyte Adhesion Deficiency-I Pyruvate Kinase Deficiency Infantile Malignant Osteopetrosis Fanconi Anemia Danon Disease Updated L
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