13 March 2019 - - The first patient has been dosed in the open-label, Phase 1 clinical trial of RP-L102, US-based multi-platform gene therapy company Rocket Pharmaceuticals, Inc.'s (NASDAQ: RCKT) lentiviral vector -based gene therapy for the treatment of Fanconi Anemia.

The patient was dosed at the Center for Definitive and Curative Medicine at Stanford University School of Medicine, the lead US clinical site.

This clinical trial will evaluate "Process B" RP-L102 which incorporates a modified cell enrichment process, transduction enhancers, and commercial-grade vector manufacturing and cell processing.

The Phase 1 clinical trial of "Process B" RP-L102 is expected to enroll 2 FA pediatric patients at the Center for Definitive and Curative Medicine at Stanford.

The study is designed to assess the safety and tolerability of a single infusion of PR-L102, as well as efficacy endpoints.

The Phase 2 study is expected to begin in the second half of 2019 following final alignment with the US Food and Drug Administration on clinical endpoints. Patients will not undergo conditioning in this trial. Further information is available here.

RP-L102 is Rocket's lentiviral vector -based gene therapy in development for patients with FA with Rocket's collaboration partners at Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) in Spain, CIBER-Rare Diseases and IIS-Fundación Jiménez Díaz.

The International Fanconi Anemia Gene Therapy Working Group helped the development of new generation of FA gene therapy programs, which began with a HIV-1-derived, self-inactivating lentiviral vector.

RP-L102's lentiviral vector carries the FANC-A gene as part of the PGK-FANCA-WPRE expression cassette which includes a phosphoglycerate kinase promoter and an optimized woodchuck hepatitis virus posttranscriptional regulatory element.

The ex vivo administration process begins with the removal and isolation of hematopoietic stem cells using a CD34+ selection process.

Autologous genetically modified CD34+ enriched hematopoietic cells (fresh or cryopreserved) are infused back into patients to restore function. RP-L102 is currently being studied in a Phase 1/2 clinical trial in the European Union with an Investigational Medicinal Product Dossier in place with the Spanish Agency for Medicines and Health Products.

RP-L102 is also being studied in a Phase 1 clinical trial in the US under the company's Investigational New Drug application for RP-L102 that utilizes "Process B" which incorporates higher cell doses, transduction enhancers, and commercial-grade vector and cell processing.

RP-L102 has been granted Orphan Drug, Fast Track, and Regenerative Medicine Advanced Therapy designations for the treatment of Fanconi Anemia type A in the United States and Advanced Therapy Medicinal Product classification and Orphan Drug designation in Europe.

Fanconi Anemia is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life.

Allogeneic hematopoietic stem cell transplantation, when available, corrects the hematologic component of FA, but requires myeloablative conditioning, which is highly toxic for the patient. HSCT is frequently complicated by graft versus host disease and also increases the risk of solid tumors, mainly squamous cell carcinomas.

Approximately 60-70% of patients with FA have a FANC-A gene mutation, which encodes for a protein essential for DNA repair. Mutation in the FANC-A gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress.

Chromosome fragility induced by DNA-alkylating agents such as mitomycin-C or diepoxybutane is the 'gold standard' test for FA diagnosis.

The DEB assay can further differentiate FA patients from somatic mosaic patients. Somatic mosaicism occurs when there is a spontaneous reversion mutation that can lead to a mixed chimerism of corrected and uncorrected bone marrow cells leading to stabilisation or correction of an FA patient's blood counts in the absence of any administered therapy.

Somatic mosaicism provides strong rationale for the development of FA gene therapy and demonstrates the selective advantage of gene-corrected hematopoietic cells in FA1.

1Soulier, J., et al. Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood 105: 1329-1336

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is an emerging, clinical-stage biotechnology company focused on developing first-in-class gene therapy treatment options for rare, devastating diseases.

Rocket's multi-platform development approach applies the well-established lentiviral vector and adeno-associated viral vector gene therapy platforms. Rocket's lead clinical programme is a LVV-based gene therapy for the treatment of Fanconi Anemia, a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer.

Rocket's additional pipeline programs for bone marrow-derived disorders are for Pyruvate Kinase Deficiency, Leukocyte Adhesion Deficiency-I (LAD-I) and Infantile Malignant Osteopetrosis. Rocket is also developing an AAV-based gene therapy program for a devastating, pediatric heart failure indication, Danon disease.