ATP7B

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

Safety and initial efficacy data from Stage 1 expected in the first half of 2024 Dose selection and initiation of Stage 2 to follow in the second half of 2024 Jan. 25, 2024 -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced that all patients have been dosed with UX701 across the three dose-escalation cohorts in Stage 1 of its pivotal Phase 1/2/3 Cyprus2+ study. The company's investigational AAV9 gene therapy is designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion, with the goal of normalizing copper metabolism in patients with Wilson disease. “With the support of patients, physicians and the Wilson disease community, we’ve completed Stage 1 enrollment in the Cyprus2+ program, which moves us one step closer to beginning Stage 2, the pivotal, randomized placebo-controlled stage of the study,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “Beyond the seamless nature of this study, another important differentiator of this program is that it leverages our Pinnacle PCL™ platform, which enabled a single run to support Stage 1, demonstrating that the productivity improvements generated by our platform are able to support larger-scale clinical programs.” Data presented in October 2023 at a Company Analyst Day demonstrated that UX701 has been well tolerated in the first dose cohort, with no unexpected related treatment emergent adverse events observed as of the data cut-off date. Four of five patients enrolled in Cohort 1 had started tapering standard-of-care treatment, including two that came completely off of chelators and/or zinc therapy. Additional interim data from all three Stage 1 dose cohorts are expected in the first half of 2024, which will be followed by dose selection and initiation of Stage 2 in the second half of 2024. Phase 1/2/3 Cyprus2+ study design This study evaluating UX701 for the potential treatment of Wilson disease is designed with three stages. During the first stage, the safety and efficacy of up to three dose levels of UX701 will be evaluated over the course of 52 weeks and a dose will be selected for further evaluation in Stage 2. In this first stage, 15 patients were enrolled into three sequential dosing cohorts to evaluate doses of 5.0 x 10^12 GC/kg, 1.0 x 10^13 GC/kg, and 2.0 x 10^13 GC/kg. In Stage 2, a new cohort of patients will be randomized 2:1 to receive the selected dose of UX701 or placebo. The primary safety and efficacy analyses will be conducted at Week 52 of Stage 2. The primary efficacy endpoints are change in 24-hour urinary copper concentration and percent reduction in standard-of-care medication by Week 52. After the initial 52-week study period, all patients will have long-term follow up in Stage 3. Wilson disease is a rare inherited disorder caused by mutations in the ATP7B gene, which results in deficient production of ATP7B, a protein that transports copper. Loss of function of this copper-binding protein results in the accumulation of copper in the liver and other tissues, most notably the central nervous system, and failure to properly distribute copper by ceruloplasmin. Patients with Wilson disease experience hepatic, neurologic and/or psychiatric problems. Those with liver disease can experience such symptoms as fatigue, lack of appetite, abdominal pain and jaundice, and can progress to fibrosis, cirrhosis, life-threatening liver failure and death. Wilson disease can be treated by reducing copper absorption or removing excess copper from the body using life-long chelation therapy, but unmet needs exist because some treated patients experience clinical deterioration and severe side effects. Wilson disease affects more than 50,000 individuals in the developed world. UX701 is an investigational AAV9 gene therapy designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion. It has been shown in preclinical studies to normalize copper trafficking and excretion from the body. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to UX701. Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease. The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency. The content above comes from the network. if any infringement, please contact us to modify.

Vivet Therapeutics Announces Presentations at Upcoming European Society of Gene and Cell Therapy (ESGCT) 2023 Annual Congress Paris, France, October 23, 2023 (GLOBE NEWSWIRE) – Vivet Therapeutics (“Vivet”), a clinical-stage biotechnology company developing novel gene therapies for rare, inherited metabolic conditions, announced its participation and presentations at the 30th European Society of Gene and Cell Therapy (ESGCT) 2023 Annual Congress. The congress will be held from October 24 – 27, 2023, in Brussels, Belgium. Dr. Nicholas Weber, Principal Scientist and Lead for New Programs and Innovations at Vivet, will present in an invited talk about adeno-associated virus (AAV) therapies targeting inherited cholestasis. Gloria Gonzalez-Aseguinolaza, Vivet Therapeutics Chief Scientific Officer, will also present new preclinical results related to its lead program VTX-801, which utilizes the proprietary recombinant AAV (rAAV) technology to target Wilson disease. The presentation and poster details are listed below; the full program is available on the ESGCT website.Session 3c: Gene therapy for metabolic diseases at preclinical stageDate/Time: Wednesday 25 Oct at 8:30.Title: INV21 – Advances and pitfalls in AAV therapy targeting inherited cholestasisPresenter: Nicholas Weber, Ph.D , Principal Scientist, Vivet TherapeuticsRoom: Maison de la Poste, PARALLEL Poster Number: P035Category: AAV & non integrative vectorsPoster Title: Improvement of progressive familial intrahepatic cholestasis type 2 via AAV-mediated hepatic BSEP expression in mice Presenter: Angie Molina, Ph.D. (Fundación para la Investigación Medica Aplicada in partnership with Vivet Therapeutics) Poster Number: P585Category: Metabolic DiseasesPoster Title: Therapeutic efficacy of VTX-801 Wilson’s disease mice at an advanced stage the disease Presenter: Gloria Gonzalez-Aseguinolaza, Ph.D ,Chief Scientific Officer, Vivet Therapeutics Number: P567Category: Metabolic DiseasesPoster Title: Therapeutic Efficacy of the Combination of Long-Term Penicillamine Treatment with a Single Administration of VTX-801 in Wilson’s Disease MicePresenter: Gloria Gonzalez-Aseguinolaza, Ph.D, Chief Scientific Officer, Vivet Therapeutics About Vivet TherapeuticsVivet Therapeutics is a biotechnology company developing transformative and novel gene therapy treatments for rare, inherited metabolic diseases.Vivet’s lead program is VTX-801, a novel investigational gene therapy being evaluated in the GATEWAY clinical trial, a Phase I/II clinical trial to determine the safety, viability, and pharmacological activity of a single intravenous infusion in adults with Wilson disease. Wilson disease is a rare genetic disorder caused by mutations in the gene encoding the ATP7B protein, which reduces the ability of the liver and other tissues to regulate copper levels, causing severe hepatic damage, neurologic symptoms and potentially death. VTX-801 has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) and the European Commission (EC). It has also received Fast Track Designation by the FDA.Vivet is building a diversified gene therapy pipeline based on novel rAAV (recombinant AAV) with five preclinical programs and new technologies addressing key challenges of AAV-based gene therapy related to the sustainability of expression in young patients and immunomodulation for potential retreatment. Vivet develops these technologies through its partnership with, and exclusive licenses from, the Fundación para la Investigación Médica Aplicada (FIMA), a not-for-profit foundation at the Centro de Investigación Medica Aplicada (CIMA), University of Navarra based in Pamplona, Spain. Visit www.vivet-therapeutics.com for more information. If you would like to meet with the Vivet team during the congress, or at any other time, please contact: info@vivet-therapeutics.com. For more information on the ongoing VTX-801 GATEWAY clinical trial, visit https://www.gatewaytrialwilsondisease.com/. https://www.linkedin.com/company/vivettherapeutics/https://twitter.com/vivet_tx