Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — 64th Annual Meeting of the American Society of Hematology (ASH) 2022
15 slides from Rocket Pharmaceuticals's conference presentation, December 2022
Slide 1: Lentiviral-Mediated Gene Therapy for Patients with Fanconi Anemia [Group A]: Updated Results
Lentiviral-Mediated Gene Therapy for Patients with Fanconi Anemia [Group A]: Updated Results from Global RP-L102 Clinical Trials Agnieszka Czechowicz, MD, PhD Center for Definitive and Curative Medicine Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regener
Slide 2: Disclosures
Disclosures • Consultant: 48 Bio, GV, Lyrik Therapeutics, Prime Medicine, Spotlight Therapeutics, Stemodontics, Teiko Bio • Current Equity: 48 Bio, Beam Therapeutics, Decibel Therapeutics, Editas Medicine, GV, Lyrik Therapeutics, Magenta Therapeutics, Prime Medicine, Spotlight Therapeutics, Stemodon
Slide 3: Introduction
Introduction Fanconi anemia (FA) is a rare inherited FA represents a significant unmet medical need disorder of defective deoxyribonucleic acid (DNA) repair characterized by: • FA complementation group A (FA-A) accounts for 60–70% of • Progressive bone marrow failure FA; prevalence of ~4,000 cases i
Slide 4: RP-L102 Rationale and Study Design
RP-L102 Rationale and Study Design • Insertion of a functional FANCA gene into autologous Schematic of Product Manufacture and Treatment FA-A CD34+ cells confers resistance to DNA-damage 1. Mobilization of CD34 + cells (G-CSF + Plerixafor) & provides proliferative advantage to modified cells • Enabl
Slide 5: Global RP-L102 Studies
Global RP-L102 Studies Key Eligibility Criteria Endpoints Inclusion: Efficacy: • FA complementation group A Engraftment: Peripheral blood (PB) and BM • Minimum age: 1y vector copy number (VCN) • Maximum age: US Ph 1 (12y); US Ph 2 (none); EU Ph 2 (17y) Phenotypic correction: Increased resistance of
Slide 6: 12 Patients Treated: Demographics and Investigational Product Metrics
12 Patients Treated: Demographics and Investigational Product Metrics Mean VCN: Age at Transduction CFC Survival All patients ≤6 years old at Enrollment Follow Up Liquid Efficiency MMC enrollment Subject # (years) (months) CD34+ Cells/kg CFCs/kg Culture CFCs (%) 10nM (%) 10 patients have ≥12 1 (1001
Slide 7: MMC Resistance in Bone Marrow Colony Forming Cells is Associated with Long-term Hematologic Stability
MMC Resistance in Bone Marrow Colony Forming Cells is Associated with Long-term Hematologic Stability • FANCOLEN-I (investigator-initiated) long-term follow-up: BM MMC-r Leukocytes Neutrophils Hemoglobin Platelets FA-2002 (246,000 cCD34+/Kg) FA-2006 (410,000 cCD34+/Kg) ≥20% BM CFC MMC resistance is
Slide 8: Progressively Increasing and Sustained Genetic Correction in 7 of 10 Patients
Progressively Increasing and Sustained Genetic Correction in 7 of 10 Patients ≥1 year post-RP-L102 PBMC VCN BM VCN Progressive increases in gene markings in PB and BM in 7 patients Not shown: PB and BM VCN in Patient 2 (1002), who was withdrawn from the study at 18 months post-RP-L102 infusion BM VC
Slide 9: Increasing Phenotypic Correction (MMC-resistance) over 1–3 Years post-RP-L102
Increasing Phenotypic Correction (MMC-resistance) over 1–3 years post-RP-L102 12m post gene therapy 20% resistance to MMC Sustained BM CFC MMC resistance observed in at least 6 patients * Not shown: MMC Resistance in Patient 2 (1002), who was withdrawn from the study at 18 months post-RP-L102 infusi
Slide 10: Increased BM CFC MMC Resistance Associated with Hematologic Stabilization
Increased BM CFC MMC Resistance Associated with Hematologic Stabilization at ≥1 year post-RP-L102 Leukocytes Neutrophils Hemoglobin Platelets Patient 3 (2004) Concomitant blood Patient 4 (2008) count stabilization over 12–36 months seen in 6/6 patients with BM Patient 5 (2009) MMC resistance ≥20% Pa
Slide 11: Increased BM CFC MMC Resistance Evident at ≥3 Years in Patient 1
Increased BM CFC MMC Resistance Evident at ≥3 years post-RP-L102 in Patient 1 (1001) Patient 1 (1001) developed BM MMC resistance of 49% at 40 months post-RP-L102 infusion and has had recent relative blood count stabilization and potentially decreasing transfusion requirements Leukocytes Neutrophils
Slide 12: RP-L102 Safety Profile Appears Highly Favorable
RP-L102 Safety Profile Appears Highly Favorable • Patients are treated without antecedent conditioning and attendant risks • No signs of bone marrow dysplasia, clonal dominance or insertional mutagenesis to date related to RP-L102 • Gene therapy does not preclude subsequent allogeneic HSCT if necess
Slide 13: Unrelated Adverse Event: T cell lymphoblastic lymphoma
Unrelated Adverse Event: T cell lymphoblastic lymphoma Lymphoma biopsy specimen demonstrated no appreciable LV integration Mean VCN: 0.00314 copies/diploid genome Patient 5 (2009) Lymphoma Biopsy Reference Standard (Mean VCN: 1.10 copies/diploid genome) WPRE Amplitude WPRE+ PTBP2– WPRE+ PTBP2+ WPRE+
Slide 14: Conclusions from Initial 10 Patients with ≥1 Year of Follow-Up
Conclusions from Initial 10 Patients with ≥1 Year of Follow-Up RP-L102 is a potentially curative therapy to prevent FA-related BMF, which can be administered without a suitable allogeneic donor or transplant-conditioning related toxicities. • RP-L102 conferred phenotypic correction as demonstrated b
Slide 15: Acknowledgements
Acknowledgements Julián Sevilla, MD, PhD Maria Grazia Roncarolo, MD, PhD Josune Zubicaray, MD, PhD Rajni Agarwal, MD Elena Sebastian, MD, PhD Juan Bueren, PhD Paula Río, PhD Susana Navarro, PhD Eileen Nicoletti, MD Michael Rothe, PhD Grace Choi John E. Wagner, MD Antonella Lucía Bastone, PhD Miriam
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