Aruvant Sciences Presents Data from Ongoing Clinical Study of Lentiviral Gene Therapy RVT-1801 for Sickle Cell Disease at 60th Annual Meeting of the American Society of Hematology

BASEL, Switzerland and NEW YORK and CINCINNATI, Dec. 3, 2018 /PRNewswire/ -- Aruvant Sciences, a clinical-stage gene therapy company focused on hematological conditions, today announced that preliminary safety and efficacy data from an ongoing Phase 1/2 study of RVT-1801 were delivered in an oral presentation by Dr. Punam Malik, Director of the Cincinnati Comprehensive Sickle Cell Center at Cincinnati Children's Hospital Medical Center, at the 60th Annual Meeting of the American Society of Hematology (ASH).

The goal of the ongoing clinical study is to assess the safety, feasibility, and efficacy of RVT-1801 for the treatment of sickle cell disease in conjunction with reduced intensity conditioning. RVT-1801 is the only known clinical-stage investigational gene therapy to deliver the gamma-globin gene for production of fetal hemoglobin (HbF). Fetal hemoglobin has very potent anti-sickling properties relative to adult hemoglobin (HbA). RVT-1801 uses a patented, modified gamma-globulin sequence to further enhance its affinity to form HbF and its anti-sickling properties.

Two patients with sickle cell disease have been administered RVT-1801 to date. Both patients received a patient-specific AruLite™ reduced intensity conditioning (RIC) regimen involving melphalan and other agents. This conditioning regimen, which is investigational and subject to further study and review, has been designed with the intention of minimizing the adverse events associated with high intensity conditioning regimens, such as busulfan, while still enabling sufficient gene-corrected CD34+ cell engraftment into the patient's bone marrow. Both patients exhibit evidence of sustained, stable, genetically-modified cells in blood and bone marrow with highly polyclonal marking over a year after the administration of RVT-1801:

• Patient 1 exhibits 31.5% of total Hb as anti-sickling hemoglobins (HbF^G16D + HbF + HbA2) with 20.2% of total Hb from HbF^G16D at 15 months after administration of RVT-1801
• Patient 2 exhibits 22.2% of total Hb as anti-sickling hemoglobins with 8.6% of total Hb from HbF^G16D at 12 months after administration of RVT-1801

Following reduced intensity conditioning and gene infusion, both patients recovered platelet counts (PLT >50k per µl) and absolute neutrophil counts (ANC >500 per µl) within 2 weeks:

• Patient 1 took 12 days to reach PLT >50k and 9 days to reach ANC >500
• Patient 2 took 7 days to reach both PLT >50k and ANC >500

Both patients show signs of reductions in disease burden:

• Patient 1 presented with 48 acute vaso-occlusive crises (VOCs) in the 18 months prior to gene infusion, and has had only 1 VOC in the 15 months after administration of RVT-1801
• Patient 2 presented with 20 acute VOCs in the 18 months prior to gene infusion, and has had no SCD-related VOCs in the 12 months after administration of RVT-1801, but has had 3 episodes of mild exacerbation of chronic pain requiring oral opioids
• Both patients have been weaned off daily opioids for their chronic pain

Both patients treated with RVT-1801 have had minimal acute toxicity to date. Approximately 80% of post-gene infusion peri-transplant adverse events were pain. Both patients had taken daily opioids chronically for several years prior to the administration of the investigational therapy. Both patients experienced transient, conditioning-related adverse events including grade 2-3 mucositis, temporary cytopenia, and temporary mild elevations in transaminases.

"Therapeutics should be designed with the patient in mind, and even more so for a disease that has an enormous global burden," said Dr. Malik. "Gene therapies that require high intensity conditioning regimens with myeloablative doses limit access to a few, and present significant risks for patients with sickle cell disease who have considerable organ damage from the disease itself. Our hope is that the unique characteristics of modified fetal hemoglobin render it sufficiently potent to allow for less intense conditioning without sacrificing clinical efficacy. The early data are very encouraging."

Dr. Malik's presentation has been selected for potential inclusion in the 2019 Highlights of ASH. Aruvant plans to continue enrollment in the ongoing clinical study and to expand the number of trial sites before initiating a larger pivotal clinical study.

About RVT-1801

RVT-1801 is an investigational gene therapy for sickle cell disease and β-thalassemia. RVT-1801 utilizes proprietary technology intended to increase functioning red blood cells by inserting a modified fetal hemoglobin gene into autologous stem cells through a lentiviral vector. Studies have indicated that sickle cell patients with elevated levels of fetal hemoglobin have fewer vaso-occlusive crises and hospitalizations, due in part to improved characteristics of fetal hemoglobin relative to adult hemoglobin. RVT-1801 is the only known clinical-stage gene therapy to deliver the gene encoding fetal hemoglobin, which has been further modified to optimize oxygen carrying capacity and anti-sickling properties.

About Sickle Cell Disease

Sickle cell disease is a progressively debilitating and life-threatening inherited red blood cell disorder that causes a patient's oxygen-carrying cells to be abnormally inflexible and sickle-shaped. Sickle cell disease causes anemia, ischemia of bone and bone marrow and other organs, attacks of pain called sickle cell crises, increased propensity to bacterial infections, stroke, and other organ pathologies that cause life-long suffering and shorten the lifespan of affected individuals.

About Aruvant Sciences

Aruvant Sciences is a clinical-stage gene therapy company in the Roivant family focused on hematological conditions, with an emphasis on helping patients suffering from sickle cell disease and β-thalassemia. The company's lead candidate, RVT-1801, is a modified fetal hemoglobin gene therapy for sickle cell disease and related hemoglobinopathies. For more information, please see www.aruvant.com.

SOURCE Aruvant Sciences

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