ATP7B

VTX-801 increased ceruloplasmin ferroxidase activity and improved liver histology Encouraging safety and tolerability with no serious adverse events reported PARIS, June 5, 2024 /PRNewswire/ -- Vivet Therapeutics ("Vivet"), a clinical stage biotech company developing novel and long-lasting gene therapies for rare inherited liver metabolic disorders, today announces the presentation of interim data on its international Phase 1/2 GATEWAY trial, evaluating the safety, pharmacodynamics, and efficacy of its lead program, VTX-801 for the treatment of Wilson Disease (WD) at the EASL Congress 2024, held in Milan, Italy. The poster presentation by Ass. Professor, Thomas Damgaard Sandahl entitled ' Interim safety results of the ongoing international phase I/II GATEWAY gene therapy trial with VTX-801 conducted in adult patients with Wilson Disease', detailed findings from Cohort 1 patients in the ongoing GATEWAY trial treated with Vivet's lead program, VTX-801, a recombinant adeno-associated viral vector (rAAV) carrying a shortened ATP7B gene under the control of a liver-specific promoter for the treatment of Wilson Disease. GATEWAY is a first-in-human, open label, 5-year follow-up, single dose escalation study being conducted to assess the safety, pharmacodynamics, and efficacy of VTX-801, with the objective of providing long lasting effects after a single intravenous administration in patients living with WD. Following evaluation, standard of care treatment may be withdrawn at 3- or 9-months post-infusion in VTX-801 responders; the response is defined based upon intravenously injected 64Cu PK profiles, which is considered to reflect the level of restoration of copper metabolism. Data presented at EASL is outlined below for the two Cohort 1 patients who received a single intravenous injection of VTX-801: Encouraging safety and tolerability, with no serious adverse events reported; an infusion associated reaction was managed with symptomatic treatment, patient discharged the next day as planned; transient, mild liver enzymes elevations occurred and managed in line with other systemic AAV gene therapies Increases from baseline of ceruloplasmin ferroxidase activity observed, demonstrating transgene activity in both patients treated Liver biopsy results showing normalisation of liver fibrosis and iron accumulation scores at year 1 post treatment Jean-Philippe Combal, Co-Founder & Chief Executive Officer at Vivet Therapeutics, said "Existing life-long oral treatments for WD are constraining and associated with side effects, leading to poor adherence and in some cases, severe WD complications. These interim data presented at EASL are encouraging for the development of an alternative treatment option for WD, following completion of Cohort 1, which demonstrated promising safety, tolerability and early pharmacodynamic changes. In Cohort 2, we have dosed the first patient with VTX-801 at an escalated dose level and we hope for a more robust pharmacodynamic response at a much higher magnitude. We are pleased so far with the progress of the study and continue with the perspective of developing VTX-801 as a potential disease-modifying treatment for people living with WD." Further details on the GATEWAY trial can be found on Clinical Trials, under identifier NCT04537377. Study authors: T. D. SANDAHL1, W. M. LEE2, A. ALA 3, R. P. GONZALEZ-PERALTA 4, V. MEDICI 5, F. K. ASKARI 6, S. RUDNICK 7, U. M. LAUER 8, H. H. SCHMIDT 9, S. VALERO10, G. GONZALEZ-ASEGUINOLAZA11, J.-P. COMBAL 10, L. d'ANTIGA 12, B. BENICHOU10 and M. L. SCHILSKY 13 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark. 2Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Royal Surrey County Hospital, Guilford, Surrey GU2 7XX, United Kingdom; 4AdventHealth for Children, AdventHealth Transplant Institute, Orlando, Florida, USA; 5Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, California, USA; 6Department of Medicine, University of Michigan, Ann Arbor, MI, USA; 7Department of Internal Medicine, Section on Gastroenterology and Hepatology, Atrium Health Wake Forest Baptist, Winston-Salem, NC, USA; 8Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany; 9Klinik für Gastroenterologie, Hepatologie und Transplantationsmedizin, Universitätsklinikum Essen, Hufelandstr. 55 D-45147 Essen; 10Sonia Valero: Vivet Therapeutics SA, Paris, France; 11Vivet Therapeutics S.L., Pamplona, Spain; 12Department of Pediatric Hepatology, Gastroenterology, Transplantation, ASST Papa Giovanni XXIII Hospital, 24127, Bergamo, Italy; 13Michael Schilsky: Department of Medicine, Section of Digestive Diseases, and Department of Surgery, Section of Transplant and Immunology, Yale School of Medicine, New Haven, CT, USA. About Vivet Therapeutics Vivet Therapeutics is a private, clinical-stage biotech company developing novel and long-lasting gene therapies for rare inherited metabolic conditions, including Wilson's Disease. Vivet's gene therapy platform uses recombinant adeno-associated viruses (rAAVs) as vectors and has initiated two clinical programs and four pre-clinical assets to date. Its most advanced therapy is VTX-801, a novel gene therapy for Wilson's Disease, with key clinical read-outs expected by the end of 2024. Vivet Therapeutics was founded in 2016 by CEO Dr Jean-Philippe Combal and CSO Dr Gloria Gonzalez-Aseguinolaza and is led by a highly experienced management team with deep expertise developing gene therapies and orphan drugs. Vivet Therapeutics is backed by international life science investors including Novartis Venture Fund, Roche Venture Fund, HealthCap, Pfizer Inc., Columbus Venture Partners, Ysios Capital, Kurma Partners and Eurazeo. In 2019, key investor Pfizer contributed a €45M investment to collaborate with Vivet in recognition of its scientific expertise and innovative technology platforms. For more information, please visit . Follow us on LinkedIn @Vivet Therapeutics and Twitter @Vivet_tx. About EASL EASL, the European Association for the Study of the Liver, founded in 1966, is a medical association dedicated to pursuing excellence in liver research, to the clinical practice of liver disorders, and to providing education to all those interested in hepatology. As of 2023, EASL serves 5,300 members from 112 countries. SOURCE Vivet Therapeutics

Dosing of first patient completed in Cohort 2 following Data Monitoring Committee approval to proceed Encouraging safety, tolerability and early pharmacodynamic changes observed in Cohort 1 with lead program VTX-801 PARIS, April 8, 2024 /PRNewswire/ -- Vivet Therapeutics ('Vivet'), a clinical stage biotech company developing novel and long-lasting gene therapies for rare inherited liver metabolic disorders, today announces that it has dosed its first patient with its lead program VTX-801 in Cohort 2 of its ongoing GATEWAY Clinical Trial for the treatment of Wilson Disease (WD). Initiation of Cohort 2 followed the successful completion of Cohort 1 and approval from an independent Data Monitoring Committee (DMC) to proceed. WD is a disorder that leads to a build-up of toxic levels of copper in the liver and brain and causes debilitating neurological and hepatic morbidity. Recent evidence indicates that WD can frequently lead to premature death, with a higher mortality rate ranging from 2 to 4 times more than in the general population, despite existing standard of care (SOC) treatments1,2. The disease affects approximately 1 in 30,000 people –12-15,000 in the US and around 17,000 in Europe. The GATEWAY clinical trial is an ongoing, actively enrolling, non-randomized, open-label Phase 1/2 trial taking place across several clinical sites in the US, UK, Germany and Denmark and is designed to assess the safety, tolerability and pharmacological activity of a single intravenous infusion of VTX-801 at increasing dose levels in adult patients with WD. Jean-Philippe Combal, Chief Executive Officer at Vivet Therapeutics, said: "Receiving DMC approval to advance to a higher dose level is highly encouraging and accelerates our ability to further inform clinical development of VTX-801, as we evaluate its potential as a disease modifying treatment option for sufferers and their families whose lives are disrupted by WD. We are encouraged by the initial safety, histological and pharmacodynamic data that VTX-801 has demonstrated to date and we are pleased that the first patient has been successfully dosed in Cohort 2 in the GATEWAY clinical trial. 2024 is shaping up to be a transformative year for Vivet and its gene therapy platform and we look forward to providing further data on our GATEWAY clinical trial at upcoming scientific conferences." Prof Michael Schilsky, Director of the Center for Excellence for Wilson Disease at Yale and Principal Investigator at the Yale clinical trial site in New Haven for the US VTX-801 clinical trial, commented: "Evaluation of VTX-801 as a treatment option for WD is making good progress with no detected serious adverse events in the first dose, Cohort 1 patients. Existing treatments for WD are lifelong and adherence to daily treatment often requiring multiple medication doses aimed at removing excess copper from the body is a serious problem. Additionally, current treatments are not universally effective and can cause adverse side effects in some patients. VTX-801 is designed to restore the normal copper metabolism by providing an engineered, fully functional version of the ATP7B copper transporter gene in the liver, and gives hope to the possibility of eliminating the need for additional medical therapy for this disorder. Early, encouraging data from Cohort 1 has shown detectable vector transduction and transgene expression with early signs of improvement in liver function and histology. We look forward to moving this ground breaking program further through the GATEWAY study and future clinical trials as we seek to demonstrate its transformative potential for patients with WD." Following approval from the DMC, Vivet has safely dosed its first patient at a higher dose level in cohort 2, based on encouraging safety, tolerability and early pharmacodynamic changes observed in two patients in Cohort 1. No unexpected treatment emergent adverse events (TEAE) were observed at the first dose level in Cohort 1. Ongoing patient monitoring in Cohort 1 has demonstrated sustained increase of ceruloplasmin enzymatic activity and ATP7B minigene mRNA hepatic expression with liver histology improvement confirmed in one biopsy at 12 months. Due to results observed with a specific radio-labelled copper(64Cu) biomarker, both patients have been deemed insufficient responders and their SOC treatments are being maintained. Further data readouts on the GATEWAY clinical trial will be reported at upcoming scientific conferences in 2024. About Vivet Therapeutics Vivet Therapeutics is a private, clinical-stage biotech company developing novel and long-lasting gene therapies for rare inherited metabolic conditions, including Wilson's Disease. Vivet's gene therapy platform uses recombinant adeno-associated viruses (rAAVs) as vectors and has initiated two clinical programs and four pre-clinical assets to date. Its most advanced therapy is VTX-801, a novel gene therapy for Wilson's Disease, with key clinical read-outs expected by the end of 2024. Vivet Therapeutics was founded in 2016 by CEO Dr Jean-Philippe Combal and CSO Dr Gloria Gonzalez-Aseguinolaza and is led by a highly experienced management team with deep expertise developing gene therapies and orphan drugs. Vivet Therapeutics is backed by international life science investors including Novartis Venture Fund, Roche Venture Fund, HealthCap, Pfizer Inc., Columbus Venture Partners, Ysios Capital, Kurma Partners and Eurazeo. In 2019, key investor Pfizer contributed a €45M investment to collaborate with Vivet in recognition of its scientific expertise and innovative technology platforms. For more information, please visit - Follow us on LinkedIn @Vivet Therapeutics and Twitter @Vivettherapeutics 1-Członkowska A, Niew ada M, Litwin T, Kraiński Ł, Skowrońska M, Piechal A, Antos A, Misztal M, Khanna I, -Kurkowska-Jastrzębska I. Seven decades of clinical experience with Wilson's disease: Report from the national reference centre in Poland. Eur J Neurol. 2022 Nov 25. doi: 10.1111/ene.15646. Epub ahead of print. PMID: 36427277. 2-Daniel-Robin T, Bénichou B, Leboucher C, Blein C, Combal JP. Epidemiology, treatment and burden of Wilson disease in France: A 10-year analysis of the national health insurance database. Clin Res Hepatol Gastroenterol. 2022 Dec;46(10):101992. doi: 10.1016/j.clinre.2022.101992. Epub 2022 Jul 3. PMID: 35793759. SOURCE Vivet Therapeutics

Vivet’s VTX-806 is an adeno-associated virus (AAV) vector gene therapy that reinstates CYP27A1 gene activity. Image Credit: Anusorn Nakdee / Shutterstock. The French Government has awarded a €4.9m ($5.3m) grant to Paris-based Vivet Therapeutics to develop VTX-806, a gene therapy to treat a rare condition that leads to the accumulation of cholesterol in nerve cells called cerebrotendinous xanthomatosis (CTX). The funding is part of the France Health Innovation Plan 2023 under the acceleration strategy of Biotherapies – Bioproduction in innovative therapies. The funding is operated by French investment bank Bpifrance and will be disbursed over three years, as per a 1 February press release. Vivet is developing gene therapies for different rare disorders and has a partnership with Pfizer , wherein the latter owns 15% equity in the company. VTX-806 is an adeno-associated virus (AAV) vector gene therapy that reinstates CYP27A1 gene activity. The therapy is being developed to stop or reverse disease progression over the long term, or to potentially cure CTX. CTX is a rare autosomal recessive genetic disorder caused by an abnormality in the CYP27A1 gene. The gene is responsible for producing mitochondrial enzyme sterol 27-hydroxylase enzyme, responsible for converting cholesterol into a bile acid. See Also: Almirall and Microsoft partner for dermatological drug development Takeda and Protagonist sign rusfertide development deal If untreated, CTX can cause progressive neurologic problems such as seizures, cognitive impairment, and ataxia. Current disease treatment includes oral bile acid replacement therapy and treatment with chenodeoxycholic acid to normalise the production of cholestanol. Vivet’s lead candidate, VTX-801, is a gene therapy for Wilson’s disease being developed with Pfizer . The AAV vector gene therapy targets the ATP7B gene, responsible for causing the condition. It is currently being investigated in an open-label Phase I/II GATEWAY trial (NCT04537377), that has a clinical readout expected by the end of the year. The study’s endpoint is to assess the safety and tolerability of VTX-801 at 52 weeks after a single infusion. Additional endpoints include changes in disease-related biomarkers, including free serum copper and serum ceruloplasmin activity, as well as radiocopper-related parameters and VTX-801 responder status to allow standard-of-care withdrawal. Other therapies in Vivet’s preclinical pipeline include VTX-804 for the treatment of a rare neurological disorder, citrullinemia type 1, along with VTX-802 and VTX-803 for the treatment of progressive familial intrahepatic cholestasis (PFIC) – a set of rare genetic disorders. In 2021, US-based Mirum Pharmaceuticals acquired development and commercialisation rights for VTX-802 and VTX-803. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. By Cytiva Thematic By downloading this case study, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy