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2932 A Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Interim ResultsClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 801. Gene Therapies: Poster II
Hematology Disease Topics & Pathways:
Clinical Trials, Biological therapies, Workforce, Gene Therapy, Therapies
Sunday, December 12, 2021, 6:00 PM-8:00 PM

Donald B. Kohn, MD1, Claire Booth, MBBS, PhD, MSc2*, Julián Sevilla, MD, PhD3*, Gayatri R Rao, MD, JD4*, Elena Almarza, PhD4,5,6*, Dayna Terrazas, RN1*, Eileen Nicoletti, MD4*, Augustine Fernandes, PhD1*, Caroline Kuo, MD1*, Satiro de Oliveira, MD1*, Theodore B. Moore, MD1, Kenneth M Law, PhD4*, Brian C Beard, PhD4*, Grace Choi, BS4*, Miriam Zeini, PhD4*, Cristina Mesa-Núñez, PhD5,6*, Adrian J. Thrasher, MBBS, PhD, FMedSci2*, Juan A Bueren, PhD5,6* and Jonathan D Schwartz, MD4

1University of California, Los Angeles, Los Angeles, CA
2UCL Great Ormond Street Institute of Child Health, London, United Kingdom
3Hematología y Hemoterapia, Fundación para la investigación Biomédica, Hospital Infantil Universitario Niño Jesús (HIUNJ), Madrid, Spain
4Rocket Pharmaceuticals, Inc., Cranbury, NJ
5Unidad de Innovación Biomédica, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Madrid, Spain
6Unidad Mixta de Terapias Avanzadas, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain

Background: Leukocyte Adhesion Deficiency-I (LAD-I) is a rare disorder of neutrophil adhesion resulting from ITGB2 mutations encoding for the β2-integrin component, CD18. Severe LAD-I (CD18 <2% of polymorphonuclear [PMN] cells) is characterized by severe infections, impaired wound healing, and childhood mortality. Allogeneic hematopoietic stem cell transplant (alloHSCT) is potentially curative; however, its efficacy is limited by donor availability and risk of graft-versus-host disease (GVHD) and graft failure. RP-L201-0318 (NCT03812263), a phase 1/2 open-label trial currently underway, employs autologous CD34+ cells transduced with a lentiviral vector (LV) carrying the ITGB2 gene (cDNA)

Methods: Pediatric patients ≥ 3 months old with severe LAD-I are eligible. HSCs are collected via apheresis after mobilization with granulocyte-colony stimulating factor (G-CSF) and plerixafor and transduced with Chim-CD18-WPRE-LV. Myeloablative therapeutic drug monitoring (TDM) busulfan conditioning precedes RP-L201 infusion. Patients are followed for safety and efficacy (i.e., survival to age 2 and at least 1-year post-infusion, increase in PMN leukocyte CD18 expression to at least 10%, peripheral blood [PB] vector copy number [VCN], decrease in infections/hospitalizations, and resolution of skin or periodontal abnormalities).

Results: Seven patients (ages 5mos-9yrs) have received RP-L201; all with follow-up ≥3 to 18 months. RP-L201 cell doses ranged from 2.8x106 to 6.5x106 CD34+ cells/kg with VCN from 1.8-3.8 copies/cell. No serious RP-L201 related treatment-emergent adverse events were reported. PB PMN CD18 expression in Patient 1 at 18-months post-treatment was 40% (vs. < 1% at baseline), with PB VCN of 1.44. Baseline skin lesions resolved with no new lesions reported. CD18 expression in the subsequent 6 patients has been 25-80% in neutrophils and stable for each patient from 3 to up to 18 months post-treatment. No new infections have been reported in patients post-infusion. The safety profile of RP-L102 remains highly favorable with no serious adverse events (SAEs) attributed to the investigational product (IP).

Conclusion: RP-L201 leads to durable neutrophil CD18 expression and improved clinical course. Additional patient treatment is ongoing in 2021.

Disclosures: Kohn: UC Regents: Patents & Royalties; Pluto Immunotherapeutics: Membership on an entity's Board of Directors or advisory committees; Allogene: Membership on an entity's Board of Directors or advisory committees; ImmunoVec: Membership on an entity's Board of Directors or advisory committees; Lyrik Therapeutics: Membership on an entity's Board of Directors or advisory committees; MyoGene Bio: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Sangamo Biosciences: Membership on an entity's Board of Directors or advisory committees. Booth: GSK: Honoraria; Takeda: Honoraria; SOBI: Consultancy, Honoraria; Orchard Therapeutics: Consultancy, Honoraria; Rocket Pharmaceuticals, Inc.: Consultancy. Sevilla: Miltenyi: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Rocket Pharmaceuticals, Inc.: Consultancy, Other: J.Sevilla is an inventor on patents on lentiviral vectors filed by CIEMAT, CIBERER and Fundación Jiménez Díaz, and may be entitled to receive financial benefits from the licensing of such patents.; SOBI: Consultancy. Rao: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Almarza: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Nicoletti: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. de Oliveira: Orchard Therapeutics: Research Funding; Bluebird Bio: Research Funding. Law: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Beard: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Choi: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Zeini: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Thrasher: Orchard Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Generation bio: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; 4Bio Capital: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rocket Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bueren: Rocket Pharmaceuticals, Inc.: Consultancy, Other: J.Bueren is an inventor on patents on lentiviral vectors filed by CIEMAT, CIBERER and Fundación Jiménez Díaz, may be entitled to receive financial benefits from the licensing of such patents and receives funding for research., Patents & Royalties, Research Funding. Schwartz: Rocket Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company.

*signifies non-member of ASH