Author: Alta Berri

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  • ARU-1801 is being developed as a potential one-time treatment for patients suffering from sickle cell disease and β-thalassemia
  • ARU-1801 has been designed to deliver a highly potent gene payload with enhanced anti-sickling properties, allowing for a Reduced Intensity Conditioning (RIC) regimen

NEW YORK and BASEL, Switzerland, Jan. 22, 2020 — Aruvant, a clinical-stage biopharmaceutical company focused on developing and commercializing transformative therapies for the treatment of severe blood disorders, today announced that the U.S. Food and Drug Administration has granted Orphan Drug designation to ARU-1801, Aruvant’s investigational therapy for the treatment of sickle cell disease.

The FDA grants Orphan Drug designation to novel therapies that treat diseases impacting fewer than 200,000 individuals in the United States. The benefits of orphan designation include a seven-year period of marketing exclusivity in the U.S. upon approval if received, waiver of certain FDA user-fees, and tax credits for qualified clinical trials.

“We are excited to build on the momentum afforded by both today’s announcement of Orphan Drug status as well as our recent announcement of Rare Pediatric Disease status for ARU-1801,” said Will Chou, M.D., Chief Executive Officer of Aruvant. “For patients suffering from sickle cell disease, we believe the ultimate promise of gene therapy is a one-time cure without the side effect profile of high intensity myeloablative conditioning. We are committed to providing patients with that option and look forward to presenting more data on our Reduced Intensity Conditioning (RIC) approach as patients continue to be treated in our ongoing Phase 1/2 study.”

About Sickle Cell Disease and β-Thalassemia

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. This genetic defect leads to lowered oxygen-carrying capacity in the hemoglobin protein of these red blood cells. Sickle cell disease can cause inflammation of extremities, bacterial infections, stroke, anemia, and attacks of pain called sickle cell crises.

β-thalassemia is an inherited red blood cell disorder distinguished by reduced or nonexistent production of functional β-globin, a critical component of adult hemoglobin. Patients with the disorder suffer from anemia, which can cause weakness, fatigue, and more serious complications. Individuals with β-thalassemia are at an increased risk of developing abnormal blood clots.

About Aruvant

Aruvant Sciences, part of the Roivant family of companies, is a clinical-stage biopharmaceutical company focused on developing and commercializing transformative therapies for the treatment of severe blood disorders, with an emphasis on helping patients suffering from sickle cell disease and β-thalassemia. The company’s lead candidate, ARU-1801, is a modified fetal hemoglobin gene therapy for sickle cell disease and related hemoglobinopathies. For more information, please visit www.aruvant.com.

About Roivant

Roivant aims to improve health by rapidly delivering innovative medicines and technologies to patients. Roivant does this by building Vants – nimble, entrepreneurial biotech and healthcare technology companies with a unique approach to sourcing talent, aligning incentives, and deploying technology to drive greater efficiency in R&D and commercialization. For more information, please visit www.roivant.com.

Contact:
Andrew Bogorad
andrew.bogorad@roivant.com

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  • ARU-1801 is being developed as a potential one-time treatment for patients suffering from sickle cell disease and β-thalassemia
  • ARU-1801 has been designed to deliver a highly potent gene payload with enhanced anti-sickling properties, allowing for a Reduced Intensity Conditioning (RIC) regimen

NEW YORK and BASEL, Switzerland, Jan. 8, 2020 — Aruvant, a clinical-stage biopharmaceutical company focused on developing and commercializing transformative therapies for the treatment of severe blood disorders, today announced that the U.S. Food and Drug Administration has granted Rare Pediatric Disease designation to ARU-1801, Aruvant’s investigational therapy for the treatment of sickle cell disease.

The FDA defines a rare pediatric disease as a serious or life-threatening disease that impacts fewer than 200,000 individuals in the United States and whose serious or life-threatening manifestations primarily affect individuals 18 years or younger. With this designation, Aruvant will be eligible to receive a priority review voucher upon approval by the FDA of a Biologics License Application for ARU-1801.

“The FDA’s Rare Pediatric Disease designation for ARU-1801 highlights the large and unmet need currently experienced by patients suffering from sickle cell disease,” said Will Chou, M.D., Chief Executive Officer of Aruvant. “Other investigational gene therapies for sickle cell disease require the use of high intensity myeloablative conditioning regimens, which are associated with lengthy hospital stays and a host of possibly serious complications. Our Reduced Intensity Conditioning (RIC) approach aims to provide patients a cure with an improved risk-benefit profile, including a lower risk of infertility and fewer days in the hospital.”

About Sickle Cell Disease and β-Thalassemia

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. This genetic defect leads to lowered oxygen-carrying capacity in the hemoglobin protein of these red blood cells. Sickle cell disease can cause inflammation of extremities, bacterial infections, stroke, anemia, and attacks of pain called sickle cell crises.

β-thalassemia is an inherited red blood cell disorder distinguished by reduced or nonexistent production of functional β-globin, a critical component of adult hemoglobin. Patients with the disorder suffer from anemia, which can cause weakness, fatigue, and more serious complications. Individuals with β-thalassemia are at an increased risk of developing abnormal blood clots.

About Aruvant

Aruvant Sciences, part of the Roivant family of companies, is a clinical-stage biopharmaceutical company focused on developing and commercializing transformative therapies for the treatment of severe blood disorders, with an emphasis on helping patients suffering from sickle cell disease and β-thalassemia. The company’s lead candidate, ARU-1801, is a modified fetal hemoglobin gene therapy for sickle cell disease and related hemoglobinopathies. For more information, please visit www.aruvant.com.

About Roivant Sciences

Roivant aims to improve health by rapidly delivering innovative medicines and technologies to patients. Roivant does this by building Vants – nimble, entrepreneurial biotech and healthcare technology companies with a unique approach to sourcing talent, aligning incentives, and deploying technology to drive greater efficiency in R&D and commercialization. For more information, please visit www.roivant.com.

Contact:

Andrew Bogorad

andrew.bogorad@roivant.com

  • Chou joins Aruvant from Novartis, where he most recently led the global commercial launch of Kymriah®, the first CAR-T cell therapy, in North America, Europe and Asia
  • Chou previously led the development and approval of Kymriah® for diffuse large B-cell lymphoma
  • He will lead Aruvant as the company prepares to dose the next cohort of patients with ARU-1801, a potentially curative investigational gene therapy for sickle cell disease administered with only reduced intensity conditioning

NEW YORK and BASEL, Switzerland, November 19, 2019 / PRNewswire / Aruvant, a clinical stage biopharmaceutical company focused on developing and commercializing transformative therapies for the treatment of severe blood disorders, today announced the appointment of William Chou, M.D. as Chief Executive Officer.

“We are thrilled to have Will join Aruvant as we transition ARU-1801 from an academic effort to a mature and scalable process in advance of a new wave of patient data prior to pivotal trial initiation,” said Dr. Frank Torti, Vant Investment Chair at Roivant Pharma. “Will’s successful track record of bringing a transformational complex cell therapy to market prepares him well to build Aruvant into a leader in gene therapy, and to fully realize the promise of Aruvant’s potential one-time transformative therapy for patients.”

Dr. Chou brings over 15 years of healthcare experience to Aruvant, having previously served in a variety of leadership roles at Novartis across both development and commercial functions. Most recently, Dr. Chou served as Vice President, Global Disease Lead for Novartis’ Cell and Gene Therapy unit, where he oversaw the global commercial launch of Kymriah®, the first CAR-T cell therapy. Prior to that role, he led the Kymriah® lymphoma clinical development program to approvals in the US, Europe, Australia, Canada and Japan.

Prior to joining Novartis, Dr. Chou worked at the Boston Consulting Group where he focused on commercial and clinical pharmaceutical strategy. Dr. Chou holds an M.B.A. from the Yale School of Management, an M.D. from the University of Pittsburgh School of Medicine, and an A.B. in politics and economics from Princeton University. Dr. Chou completed his residency in internal medicine at Yale New Haven Hospital and his fellowship in geriatrics at Yale University.

ARU-1801, the lead candidate in Aruvant’s pipeline, is an investigational lentiviral gene therapy for sickle cell disease and transfusion-dependent β-thalassemia. ARU-1801 incorporates a patented gene payload for a modified gamma-globin delivered into autologous stem cells via a proprietary vector construct, with the aim of restoring normal red blood cell function through increased levels of fetal hemoglobin. The high potency of the modified gamma globin enables ARU-1801 engraftment with only Reduced Intensity Conditioning (RIC). Preliminary clinical data from an ongoing Phase 1/2 study in patients with sickle cell disease demonstrated continuing durable reductions in disease burden and cessation of daily opioid use for over 18 months of follow-up. This data was recognized last December at the 2018 American Society of Hematology’s (ASH) annual meeting as a “Highlight of ASH,” as well as at the 2019 Sickle Cell Disease Association of America’s (SCDAA) annual meeting, where it was awarded “Best Oral Presentation.”

“I am incredibly excited to lead Aruvant on its mission to bring new hope to patients who have been waiting for transformative, potentially curative therapies,” said Dr. Chou. “ARU-1801 has the potential to dramatically change the disease trajectory in patients with sickle cell disease and transfusion-dependent β-thalassemia. The opportunity to achieve this goal with only reduced-intensity conditioning could make a meaningful difference to the well-being of patients and to the health care system. I look forward to continuing the great progress the Aruvant team has made to date.”

About Sickle Cell Disease and β-Thalassemia

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. This genetic defect leads to lowered oxygen-carrying capacity in the hemoglobin protein of these red blood cells. Sickle cell disease can cause inflammation of extremities, bacterial infections, stroke, anemia, and attacks of pain called sickle cell crises.

β-thalassemia is an inherited red blood cell disorder distinguished by reduced or nonexistent production of functional β-globin, a critical component of adult hemoglobin. Patients with the disorder suffer from anemia, which can cause weakness, fatigue, and more serious complications. Individuals with β-thalassemia are at an increased risk of developing abnormal blood clots.

About Aruvant

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

About Roivant Sciences

Roivant aims to improve health by rapidly delivering innovative medicines and technologies to patients. Roivant does this by building Vants – nimble, entrepreneurial biotech and healthcare technology companies with a unique approach to sourcing talent, aligning incentives, and deploying technology to drive greater efficiency in R&D and commercialization. For more information, please visit www.roivant.com.

Contact:
Paul Davis

Paul.davis@roivant.com

(646) 495-5310

  • Two patients have been administered RVT-1801 in conjunction with reduced intensity conditioning regimens
  • Both patients exhibit evidence of sustained, stable, genetically-modified cells in blood and bone marrow over a year after receiving treatment

BASEL, 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 (HbFG16D + HbF + HbA2) with 20.2% of total Hb from HbFG16D 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 HbFG16D 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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