RVT-1801 / Roivant - LARVOL DELTA

MOMENTUM: Gene Transfer for Patients With Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=7 | Terminated | Sponsor: Children's Hospital Medical Center, Cincinnati | Active, not recruiting ➔ Terminated; Sponsor decision due to funding

Trial termination • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease • CD34

MOMENTUM: Gene Transfer for Patients With Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=7 | Active, not recruiting | Sponsor: Children's Hospital Medical Center, Cincinnati | Trial completion date: Jun 2035 ➔ Jul 2038 | Trial primary completion date: Jun 2023 ➔ Jul 2037

Trial completion date • Trial primary completion date • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34

STABLE TRANSDUCTION OF FETAL HEMOGLOBIN IN PATIENTS WITH SICKLE CELL DISEASE IN THE PHASE 1/2 MOMENTUM STUDY OF ARU-1801 GENE THERAPY AND REDUCED INTENSITY CONDITIONING (EHA 2022) - P1/2 | "Aims H ere, we demonstrate stable, high levels of HSC engraftment in patients treated with ARU-1801 gene therapy after RIC melphalan. We have previously shown (1) ARU-1801 can reach effective levels of anti-sickling hemoglobin at VCN ≤1, with 42% HbF G16D expression per DP VCN and (2) HbF G16D may have a more potent anti-sickling effect than endogenous HbF. Along with these effects, strong long-term HSC engraftment (as demonstrated by high, stable ratios of PB to DP VCN) requiring only RIC makes ARU-1801 a promising gene therapy alternative to treatments that require myeloablative conditioning, offering amelioration of SCD phenotype without the toxicities and resource utilization of full myeloablation."

Clinical • P1/2 data • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Pain • Sickle Cell Disease • Thrombocytopenia • CD34 • SCD

Safety and Efficacy of Aru-1801 in Patients with Sickle Cell Disease: Early Results from the Phase 1/2 Momentum Study of a Modified Gamma Globin Gene Therapy and Reduced Intensity Conditioning (ASH 2021) - P1/2 | "Amelioration of SCD phenotype and engraftment of ARU-1801 gene-modified HSCs is possible with a single RIC dose of melphalan, as demonstrated in three patients. The first patient shows 27% HbF expression at three years, and 93% reduction in VOEs. The second patient had lower HSC engraftment due to below-target melphalan exposure (likely caused by renal hyperfiltration), with 14% HbF and 5% HbA2 at three years."

Clinical • P1/2 data • Anemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Pain • Sickle Cell Disease • Thrombocytopenia • Transplantation • CD34

[VIRTUAL] Early Results from a Phase 1/2 Study of Aru-1801 Gene Therapy for Sickle Cell Disease (SCD): Manufacturing Process Enhancements Improve Efficacy of a Modified Gamma Globin Lentivirus Vector and Reduced Intensity Conditioning Transplant (ASH 2020) - P1/2 | "Manufacturing process improvements in Process II included optimized timing of HSCP collection after plerixafor mobilization, LV production and improved HSCP transduction. We show that engraftment of ARU-1801 and amelioration of disease is possible with RIC using IV melphalan, with persistent stable ASG expression and meaningful improvement in VOEs in P1 and P2. P1 shows stable HbFG16D and high ASG despite low, albeit stable VCN. P2 had lower HSCP engraftment, which we hypothesize was due to below target melphalan exposure."

Clinical • P1/2 data • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD34

MOMENTUM: Gene Transfer for Patients With Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=7 | Active, not recruiting | Sponsor: Aruvant Sciences GmbH | Recruiting ➔ Active, not recruiting | N=10 ➔ 7

Enrollment change • Enrollment closed • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34

High Anti-Sickling Potency of a Gamma Globin in the Phase 1/2 MOMENTUM Study of ARU-1801 Gene Therapy and Reduced Intensity Conditioning for Sickle Cell Disease (ASGCT 2022) - P1/2 | "Prior to infusion of ARU-1801, all patients received a single intravenous dose of RIC melphalan (140 mg/m2). ARU-1801 delivers a potent anti-sickling HbFG16D with RIC, making it a promising gene therapy alternative to therapies that require myeloablative conditioning and offering amelioration of SCD symptoms without the toxicities and resources associated with full myeloablation."

P1/2 data • Anemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Neutropenia • Pain • Sickle Cell Disease • Thrombocytopenia • Transplantation • SCD

[VIRTUAL] TOWARDS PATIENT-SPECIFIC DOSING OF MELPHALAN CONDITIONING FOR ARU-1801, A NOVEL GENE THERAPY FOR TREATMENT OF SICKLE CELL DISEASE (EHA 2021) - "Background Sickle cell disease (SCD) is a severe genetic disease for which the only cure is allogeneic hematopoietic stem cell transplant (HSCT), but this procedure requires myeloablative conditioning (usually with busulfan) to allow donor cell engraftment at the risk of chemotherapy-related toxicities, including short-term (e.g. neutropenia, veno-occlusive disease) and long-term (e.g. ovarian failure, secondary leukemia) effects. These data suggest individualized melphalan dosing prior to ARU-1801 infusion may be feasible; additional data will be used to refine the PK model for patients with SCD. A simple melphalan dose adjustment algorithm based on few covariate values has the potential to reduce variability and optimize melphalan exposure, which may result in improved patient outcomes after treatment with ARU-1801."

Clinical • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Multiple Myeloma • Neutropenia • Oncology • Sickle Cell Disease • Transplantation • CD34 • CST3

MOMENTUM: Gene Transfer for Patients With Sickle Cell Disease (clinicaltrials.gov) - P1/2; N=10; Recruiting; Sponsor: Aruvant Sciences GmbH; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34

[VIRTUAL] Aruvant Sciences (BIO 2021) - "For more information on the ongoing ARU-1801 clinical study, please visit www.momentumtrials.com and for more on the company, please visit www.aruvant.com . Follow Aruvant on Facebook , Twitter @AruvantSciences and on Instagram @Aruvant_Sciences ."

Gene Therapies • Rare Diseases

[VIRTUAL] Early Results from a Phase 1/2 Study of ARU-1801 Gene Therapy for Sickle Cell Disease (FSCDR 2021) - No abstract available

P1/2 data • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

[VIRTUAL] Early Results from a Phase 1/2 Study of ARU-1801 Gene Therapy for Sickle Cell Disease (SCD): Safety and Efficacy of a Modified Gamma Globin Lentivirus Vector and Reduced Intensity Conditioning Transplant (ASGCT 2021) - P1/2 | "P2 had a sub-therapeutic exposure to melphalan secondary to renal hyperfiltration and rapid clearance of melphalan, resulting in lower engraftment. The corresponding cumulative days in hospital associated with those VOEs has decreased from 1-91 days (median, 15) to 0-17 (median, 0), representing an average 93.8% reduction. These results are an encouraging sign of the therapeutic benefit of ARU-1801 with RIC for patients with SCD."

Clinical • P1/2 data • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD34

Gene Transfer for Patients With Sickle Cell Disease (clinicaltrials.gov) - P1/2; N=10; Active, not recruiting; Sponsor: Aruvant Sciences GmbH; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease • CD34

Aruvant Announces the European Medicines Agency (EMA) Granted Priority Medicines (PRIME) Designation to ARU-1801 for the Treatment of Sickle Cell Disease (Yahoo Finance) - "Aruvant Sciences...announced that the European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to ARU-1801, a one-time investigational gene therapy for sickle cell disease (SCD)....ARU-1801 was designated PRIME status based on clinical data from the MOMENTUM study, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, that demonstrate meaningful, durable reductions in disease burden."

European regulatory • Sickle Cell Disease

Aruvant Chooses Lonza to Manufacture ARU-1801, a Potentially Curative Treatment for Sickle Cell Disease, for Pivotal Trial (PRNewswire) - "Aruvant Sciences...and Lonza announced today their agreement in support of ARU-1801, Aruvant's one-time investigational gene therapy for sickle cell disease (SCD). Aruvant has chosen Lonza to help develop and manufacture ARU-1801 for its upcoming pivotal trial."

Licensing / partnership • Sickle Cell Disease

Aruvant's Data Presented in Oral Presentation at the 62nd American Society of Hematology (ASH) Annual Meeting Demonstrates Promise of ARU-1801 as a Potentially Curative Treatment for Sickle Cell Disease (PRNewswire) - "Aruvant Sciences...announced new data demonstrating the potentially curative effect of ARU-1801 as a one-time investigational gene therapy for sickle cell disease (SCD) during an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition....Aruvant is conducting the MOMENTUM study, which is evaluating ARU-1801, a one-time potentially curative investigational gene therapy for patients with SCD. This Phase 1/2 study is currently enrolling participants..."

Clinical data • Trial status • Sickle Cell Disease

ARU-1801 Gene Therapy Granted Orphan Drug Status in EU (Sickle Cell Anemia News) - "The European Medicines Agency (EMA) has granted the designation of orphan drug to ARU-1801, an experimental gene therapy being developed by Aruvant, for the treatment of sickle cell disease (SCD)."

Orphan drug • Sickle Cell Disease

Aruvant Announces Updated Data to be Presented in Oral Presentation of ARU-1801 Data at the 62nd American Society of Hematology (ASH) Annual Meeting (PRNewswire) - "Data presented at ASH is from the MOMENTUM study, an open label Phase 1/2 clinical trial examining ARU-1801 as a one-time potentially curative gene therapy for individuals with sickle cell disease (SCD). The MOMENTUM study, which continues to enroll patients, examines ARU-1801, an autologous cell therapy leveraging a modified gamma globin lentivirus vector, in individuals with severe SCD. Unlike investigational gene therapies that require fully myeloablative conditioning, ARU-1801 is given with reduced intensity conditioning (RIC), which is a lower dose chemotherapy."

P1/2 data • Hematological Disorders • Sickle Cell Disease

Gene Transfer for Patients With Sickle Cell Disease (clinicaltrials.gov) - P1/2; N=10; Recruiting; Sponsor: Aruvant Sciences GmbH; Trial completion date: Dec 2035 ➔ Jun 2035; Trial primary completion date: Dec 2035 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease

FDA names potential gene therapy for sickle cell an ‘Orphan Drug,’ Aruvant announces (Sickle Cell Anemia News) - "A potential gene therapy for sickle cell disease (SCD) and beta-thalassemia, known as ARU-1801, has been named an orphan drug by the U.S. Food and Drug Administration (FDA), a status that helps to advance and support its development."

Orphan drug

Aruvant receives FDA Rare Pediatric Disease designation for ARU-1801 for the treatment of sickle cell disease (PRNewswire) - "Aruvant...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....Aruvant will be eligible to receive a priority review voucher upon approval by the FDA of a Biologics License Application for ARU-1801."

Regulatory

Gene Therapy for Sickle Cell Disease (SCD) Using RVT-1801 Lentivirus Vector and Arulite Reduced Intensity Conditioning Transplant Shows Promising Correction of the Disease Phenotype (ASGCT 2019) - P1, P1/2; "Myeloablative busulfan conditioning and transplant of autologous anti-sickling beta87-globin gene modified hematopoietic stem cells (HSC) was shown to cure a child with SCD (NEJM 2017)...Eligible adults with severe SCD underwent HSC collection via bone marrow (BM) harvests and/or plerixafor mobilized Peripheral Blood Stem Collection (PBSC)...80% of the AEs were pain events; others were anticipated transient laboratory AEs associated with melphalan...Both patients have sufficient anti-sickling globin expression to ameliorate anemia and remarkably reduce chronic pain and acute sickle events to date. These results with AruLite RIC, are promising and if replicated in future patients will provide a ‘transportable’ and feasible gene therapy for SCD."