ceruloplasmin

NOVATO, Calif., Oct. 03, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today reported that the Phase 1/2/3 Cyprus 2+ study of its UX701 gene therapy has demonstrated meaningful clinical activity as well as improvements in copper metabolism in Stage 1. Multiple responders have completely tapered off of standard-of-care treatment with responses seen in all three dose cohorts. The company plans to enroll an additional cohort in Stage 1 at a moderately increased dose and with an optimized immunomodulation regimen to enhance the efficiency and efficacy of the gene therapy, with the objective of having the majority of patients come off of standard-of-care treatment before selecting a dose for the randomized placebo-controlled stage of the study. In Stage 1, 15 patients were enrolled into three sequential dosing cohorts and followed for at least 24 weeks. Six of the patients have completely tapered off of standard-of-care treatment with chelators and/or zinc therapy, and a seventh patient has begun to taper as of the data cut-off date in August. In patients who have tapered off standard-of-care, non-ceruloplasmin bound copper (NCC) has stabilized to normal, healthy levels. In some patients, there were increases in ceruloplasmin-copper activity consistent with improved ATP7b function. From a safety perspective, UX701 has been well tolerated, with no unexpected related treatment emergent adverse events and no significant immunologic safety events as of the data cut-off. The company will be submitting a protocol amendment for the additional cohort at a moderately increased dose and with an optimized immunomodulation regimen to optimize delivery efficiency and efficacy for the AAV vector. “We are encouraged by the clinical activity we’re seeing with UX701 at this interim timepoint, with clear signals of transgene expression and improved trafficking of copper in a subset of patients currently enrolled in the study. These results, in addition to a number of patients tapering off of standard-of-care, give us confidence that this could ultimately be a novel therapy for people living with Wilson disease,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “A higher dose and optimized immunomodulation should enhance the clinical effect of this gene therapy and the ability to remove current standard-of-care in an even broader set of patients.” U.S. residents can learn more by visiting . Phase 1/2/3 Cyprus 2+ Study Design This study evaluating UX701 for the potential treatment of Wilson disease is designed with three stages. During the first stage (Stage 1), the safety and efficacy of multiple dose levels of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2. To date, 15 patients have been 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. A fourth dosing cohort will be added and all patients in Stage 1 will be evaluated over the course of 52 weeks. 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. About Wilson Disease 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 people in commercially accessible geographies. About UX701 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. UX701 has been granted Orphan Drug Designation in the United States and European Union and Fast Track Designation in the United States. About Ultragenyx Pharmaceutical Inc. 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. For more information on Ultragenyx, please visit the company’s website at: . Ultragenyx Forward-Looking Statements and Use of Digital Media Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx’s expectations and projections regarding its future operating results and financial performance, business plans and objectives for UX701, expectations regarding the tolerability and safety of UX701, and future clinical and regulatory developments for UX701 are forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the company to successfully develop UX701, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf , smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 2, 2024, and its subsequent periodic reports filed with the SEC. In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website ( ) and LinkedIn website ( ). Contacts Ultragenyx Pharmaceutical Inc. Investors Joshua Higa +1-415-475-6370 ir@ultragenyx.com Media Carolyn Wang +1-415-225-5050 media@ultragenyx.com

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