Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — Investor Day (December 2020)
41 slides from Rocket Pharmaceuticals's investor day presentation, Dec 7, 2020
Slide 1: ASH 2020: Investor & Analyst Event
ASH 2020: Investor & Analyst Event December 7, 2020 SEEKING GENE THERAPY CURES 1
Slide 2: Participants
Participants Gaurav Shah, MD Maria Grazia Roncarolo, MD Chief Executive Officer and President, Professor in Stem Cell and Regenerative Medicine; Rocket Pharmaceuticals Professor of Pediatrics, Medicine; Co-Director of the Institute for Stem Cell Biology and Regenerative Kinnari Patel, PharmD, MBA Me
Slide 3: Agenda
Agenda • Opening Remarks 1 • Claudine Prowse, PhD—SVP, Strategy & Corporate Development • RP-L102: Fanconi Anemia 2 • Gaurav Shah, MD—Chief Executive Officer & President • RP-L301: Pyruvate Kinase Deficiency 3 • Jonathan Schwartz, MD—Chief Medical Officer & Clinical Development, SVP • RP-L201: Leuko
Slide 4: 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 the safety, effectiveness and timing of product candidates th
Slide 5: RP-L102: Fanconi Anemia
RP-L102: Fanconi Anemia rocket
Slide 6: What is Fanconi Anemia (FA)?
What is Fanconi Anemia (FA)? • FA: a rare genetic DNA repair disorder • Background: mutations in FANC family of genes which are involved in DNA repair DNA double- Fanconi anemia complex • FANCA mutations: 60-70% of cases strand B C DNA break A M repaired F E L • Disease Sequelae: Birth defects, deve
Slide 7: FANCOLEN-I: Proof of Concept & Key Takeaways
FANCOLEN-I: Proof of Concept & Key Takeaways • Study utilized academic “Process A” • 9 pediatric patients1 have been treated (enrollment complete) • Patients had varying degrees of bone marrow health at baseline and received a wide range of drug product CD34+ cell numbers and VCN • Favorable engraft
Slide 8: Potential to Correct Bone Marrow Defect Without Conditioning to Prevent Hematologic Failure
Potential to Correct Bone Marrow Defect Without Conditioning to Prevent Hematologic Failure Gene Therapy Value Proposition: • Potential to correct blood & bone marrow defect without conditioning • GTx implemented as preventative measure to avert bone marrow failure; BMT is indicated for patients in
Slide 9: RP-L102 Pivotal Clinical Trials and Outcome Measures
RP-L102 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 processing Inclusion
Slide 10: 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 11: 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 12: 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 13: 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 14: 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 Optimal means of the nine patients treated in Fancolen-I the two that had the best benefit risk 14
Slide 15: Increasing Proportion of Gene-Corrected Cells in Peripheral Blood
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 16: 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 17: 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 18: RP-L301: Pyruvate Kinase Deficiency
RP-L301: Pyruvate Kinase Deficiency 18
Slide 19: What is Pyruvate Kinase Deficiency (PKD)?
What is Pyruvate Kinase Deficiency (PKD)? • PKD: rare inherited hemolytic anemia, caused by PKLR gene mutation • Background: results in decreased red cell pyruvate kinase activity, impaired erythrocyte metabolism and diminished red blood cell OVERVIEW: 2 lifespan. O O- 2 ADP ATP O O- • Characterized
Slide 20: 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 21: 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 22: 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 23: RP-L301: Preliminary Efficacy Results—Patient 1001
RP-L301: Preliminary Efficacy Results—Patient 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 23 Data as of October 2020
Slide 24: 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 25: 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 26: 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 27: RP-L201: Leukocyte Adhesion Deficiency-I
RP-L201: Leukocyte Adhesion Deficiency-I 27 LAD is CIRM funded
Slide 28: What is Leukocyte Adhesion Deficiency-I (LAD-I)?
What is Leukocyte Adhesion Deficiency-I (LAD-I)? • Mutations in the ITGB2 gene encoding for β2-integrin common chain (CD18) • Prevents expression of functional CD18/CD11 heterodimers on WBC cell surface • Leukocytes unable to leave bloodstream and migrate to sites of infection • Characterized by rec
Slide 29: Clinical Pathogenesis of LAD-I
Clinical Pathogenesis of LAD-I LAD-I Disease Spectrum Kaplan-Meier Survival Estimates by Neutrophil CD18 Expression -Patients with LAD-I not receiving allogeneic HSCT- Severe: Moderate: <2% 2-30% CD18+ PMN CD18+ PMN PMN = polymorphonuclear neutrophils LAD-I Clinical Prognosis • Patients suffer from
Slide 30: RP-L201 Clinical Trial Design and Status
RP-L201 Clinical Trial Design and Status Design Adaptive DP Phase N (Planned) N (Treated) Phase 1/2 Manufactured Study 1 2 2 2 2 7 5 2 Total 9 7 4 Primary Outcomes • Phase 1: Safety & preliminary efficacy • Phase 2: o Survival: proportion of patients alive at age 2 and at least 1-year post infusion
Slide 31: 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 9-y.o. female • Drug Product VCN: 3.8 diagnosed with severe LAD-I at age 7 % CD18 Expression (PMN) VCN (PBMC) 36 PMN: polymorphonuclear lymphocytes PBMC: peripheral blood mononuclear cell 31
Slide 32: 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 33: 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 3-y.o. female • Drug Product VCN: 2.5 diagnosed with severe LAD-I at age 3 % CD18 Expression (PMN) VCN (PBMC) CD18 at baseline was reported as dim in approximately 63% PMNs, likely indicating an unstable p
Slide 34: Patient 2006: 2-Month Follow-up
Patient 2006: 2-Month Follow-up KEY DRUG PRODUCT METRICS 7-m.o. male CD34+ Cell Dose: Drug Product VCN: diagnosed at birth 4.3 x 106 cells/kg 2.87 76% CD18 expression at 2- Clinically stable Hematopoietic month with no reported reconstitution timepoint serious adverse observed post- events post- inf
Slide 35: 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 36: Rocket Pharma
pharma
Slide 37: Question & Answer Panelists
Question & Answer Panelists Gaurav Shah, MD Maria Grazia Roncarolo, MD Chief Executive Officer and President, Rocket Professor in Stem Cell and Regenerative Medicine; Pharmaceuticals Professor of Pediatrics, Medicine; Co-Director of the Institute for Stem Cell Biology and Regenerative Kinnari Patel,
Slide 38: Appendix
Appendix rocket
Slide 39: Process A: Bone Marrow Engraftment
Process A: Bone Marrow Engraftment First Demonstration of Engraftment Without Conditioning (“Process A”—non-optimized—RP-L102) pVCN: Product VCN * * 100 1 .0 0 30 0 .3 0 e n e m a r k e d c e lls a r k e d ccells marked cells e lls C o p ie s p e r g e n o m e Copies per genome C o p ie s p e r g e
Slide 40: Process A: Functional Correction of Bone Marrow
Process A: Functional Correction of Bone Marrow Progressive Phenotypic Correction of BM Cells (MMC-Resistance) Y = 0 .9 3 * X + 2 .6 3 R = 0 .8 3 100 80 MMC Survival (%) M M C S u r v iv a l (% ) e s is ta n c e M C rResistance 60 10 40 M MMC 20 1 Months m o n th s P o s t-G T 0 6 12 24 36 0 6 12 24
Slide 41: Process A: Gene Therapy Stabilizes and Improves Previously Declining Blood Counts
Process A: Gene Therapy Stabilizes and Improves Previously Declining Blood Counts 3 3000 0 16 4 16 N Ne eu ut rtor op ph hi l isl s( x( x1 10 00 00 0/ / l) l) 4 PPl laatteel leettss ((xx11000000/ / l)l) 2 2000 0 1 14 1000 0 14 02002 (Cryo) 1 1000 3 ( g/ d/ dLL) ) 0 3 8 80 12 12 * 2.5x105 cCD34+/
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