CYP7A1

Vivet Therapeutics Presents Three Posters on Cerebrotendinous Xanthomatosis Program and Novel AAV Gene Delivery Platform at European Society of Gene and Cell Therapy Annual Congress 2024 Paris, France, October 22, 2024 – 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 three posters demonstrating key pre-clinical findings for its gene therapy program, VTX-806 for the treatment of Cerebrotendinous Xanthomatosis (CTX), a study on S/MAR-containing AAV vector integration in hereditary tyrosinemia type I (HT1) and validation of the translational value of the B6.129-Cyp27a1tmlEl t/J CTX mouse model at the European Society for Gene and Cell Therapy (ESGCT) 2024 Congress Rome, Italy from the 22-25 October. Dr Gloria Gonzalez-Aseguinolaza, Co-Founder & Chief Scientific Officer at Vivet Therapeutics, said, “Our findings highlight the potential of our diversified gene therapy pipeline, using our precise, highly engineered, next-generation viral vectors and gene constructs. We are committed to developing long-lasting AAV-based gene therapies for CTX and other rare inherited liver metabolic disorders to ultimately provide more effective treatment options for patients. Dr Jean-Philippe Combal, Co-Founder & Chief Executive Officer at Vivet Therapeutics added, “The existing standard of care (SOC) for CTX is a lifelong treatment using chenodeoxycholic acid which reduces the levels of toxic metabolites but does not 100% prevent neurodegeneration, leaving an unmet medical need. Our preclinical findings for VTX-806 provide further evidence that VTX-806 holds promise for curative treatment for CTX as underlined by our data and the European Orphan Drug Designation received in September of this year. We look forward to presenting further groundbreaking data at upcoming scientific conferences as we drive the program forward.” Poster one entitled “Long-term metabolic, phenotypic, and neuropathological characterization of the Cyp27a1-/- mouse model of cerebrotendinous xanthomatosis,” details the long-term evaluation of B6.129-Cyp27a1tmlEl t/J, a CTX mouse model with full metabolic, phenotypic, histological and neuropathological characterization up to 18 months of age. The study confirmed prior literature in that Cyp27a1-/- mice when compared to their wild-type (WT) littermates, had hepatomegaly, increased levels of plasma ALT, and increased expression of Cyp7a1 and Cyp3a11. Cyp3a11 is a homolog to human CYP3A4, an enzyme that metabolizes large portions of drugs and other foreign objects in the body. At six months of age, Cyp27a1-/- mice presented lower body weight gain and steatosis, alongside elevated toxic bile acid precursors in circulation and in the brain. In addition, Cyp27a1-/- mice presented signs of ataxia, particularly in females, making this study the first to show measurable motor alterations in a mouse model with CTX, like those described in CTX patients, making this a valuable model for translational CTX research. Poster two entitled “S/MAR-Containing AAV Vectors Result in an Increase in AAV Episomes and a Reduction in AAV Integration Sites in a Mouse Model With a High Rate of Hepatocyte Proliferation,” details an S/MAR (scaffold/matrix attachment region) containing AAV vector integration study in an HT1 mouse model (Fah1R Tyrc/RJ). Results showed that the S/MAR-containing AAVs achieved a higher therapeutic effect than the control vector. Surviving mice showed body weight (BW) and serum biomarker (SB) normalization after approximately 50 days post-injection and the number of viral genomes and disease-associated enzyme (Hfah) expression levels were similar across experimental groups. Immunohistochemistry (IHC) also showed FAH expression in clusters of positive hepatocytes in recovered mice, suggesting potential AAV integration and clonal expansion. These results not only indicate the presence of the S/MAR sequence but also suggest the location of the S/MAR sequence within the therapeutic vector, influences the fate of the viral genome in the transduced cell. Poster three entitled “Liver-directed gene therapy normalizes toxic bile acid metabolite levels in the blood and brain of mice with cerebrotendinous xanthomatosis,” details the development and optimization of VTX-806, as an adeno-associated virus (AAV) vector with high potency and low immunogenicity. AAVs were optimized using Cyp27a1 expression cassettes containing a liver-specific promoter designed to prevent potential activation of an innate immune response and added regulatory elements: minute virus of mice small intron (MVM) and Woodchuck Hepatitis Virus post-transcriptional regulatory element (WPRE). Results demonstrated in vitro and in vivo higher Cyp27a1 expression with VTX-806, restoring normal levels of circulating 7αC4, expression of hepatic bile acid synthesis-related genes, and corrected hepatomegaly. Importantly, normal levels of 7αC4 were restored in the brain. These results demonstrate for the first time that liver-directed AAV gene therapy can normalize levels of toxic metabolites in the brain, offering a potentially effective and curative treatment option for CTX patients. Details of poster presentations are as follow: Poster Title: Long-term metabolic, phenotypic, and neuropathological characterization of the Cyp27a1-/- mouse model of cerebrotendinous xanthomatosis Poster Number: P0381Presenter: Laia Trigueros Motos, Research Scientist at Vivet TherapeuticsDate and Time: Tuesday 22 October at 19:30-21:00 CESTLocation: Forum Poster Title: S/MAR-Containing AAV Vectors Result in an Increase in AAV Episomes and a Reduction in AAV Integration Sites in a Mouse Model With a High Rate of Hepatocyte Proliferation Poster Number: P0138Presenter: Andrea Llanos Ardaiz, PhD Apprentice at Vivet TherapeuticsDate and Time: Wednesday 23 October at 13:30-15:00 CESTLocation: Concourse Level – 1 and Mezzanine Concourse Poster Title: Liver-directed gene therapy normalizes toxic bile acid metabolite levels in the blood and brain of mice with cerebrotendinous xanthomatosis Poster Number: P0888Presenter: Laia Trigueros Motos, Research Scientist at Vivet TherapeuticsDate and Time: Thursday 24 October at 18:00-19:30 CESTLocation: Concourse Level – 1 and Mezzanine Concourse Poster 1 Authors: L Trigueros-Motos3,‡, A Molina1,2,‡, G Pérez1,2, I Marcilla1,2, M Molina1,2, L Neri3, D Moreno-Luqui1,2, A Douar4, JP Combal4, A García-Osta 1,2, M Cuadrado-Tejedor 1,2, B Tamarit4, C Bouquet4, G Despres5, P Krasniqi5, A Lamazière5, 6, R Hernandez-Alcoceba1, G González-Aseguinolaza1,2,3,* 1 Division of DNA and RNA Medicine, CIMA, University of Navarra, Pamplona, Spain 2 Institute for Sanitary Research (IdiSNA), Pamplona, Spain 3 Vivet Therapeutics S.L., Spain 4 Vivet Therapeutics S.A.S., Paris, France 5 Sorbonne Université, Saint Antoine Research Center, INSERM UMR 938, Paris, France 6 Département de Métabolomique Clinique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France ‡Equal contribution, *ggonzalez@vivet-therapeutics.com Poster 2 Authors: A Llanos-Ardaiz1, A Lantero1, M Ruiz de Galarreta1, L Neri1, I Mauleón 2, M Bilbao-Arribas 2,3, B Tamarit4, V Ferrer4, A Douar4, JP Combal4, R Aldabe2, G Gonzalez-Aseguinolaza 1,2 1 Vivet Therapeutics S.L., Pamplona, Spain. 2 DNA & RNA Medicine Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. 3 IdISNA, Navarra Institute for Health Research, Pamplona, Spain. 4 Vivet Therapeutics S.A.S., Paris, France Poster 3 Authors: A Molina1,2,‡, L Trigueros-Moto 3,‡, G Pérez1,2, M Molina1,2, I Marcilla-García1,2, L Neri3, A Douar4, JP Combal4, B Tamarit4, C Bouquet 4, P Krasniqi 5, A Lamazière5, 6, R Hernandez-Alcoceba1, G González-Aseguinolaza1,2,3,* 1 Division of DNA and RNA Medicine, CIMA, University of Navarra, Pamplona, Spain 2 Institute for Sanitary Research (IdiSNA), Pamplona, Spain 3 Vivet Therapeutics S.L., Spain 4 Vivet Therapeutics S.A.S., Paris, France 5 Sorbonne Université, Saint Antoine Research Center, INSERM UMR 938, Paris, France 6 Département de Métabolomique Clinique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France ‡Equal contribution, *ggonzalez@vivet-therapeutics.com -Ends- For further information, please contact: Optimum Strategic Communications Mary Clark, Zoe Bolt, Vareen OuthonesackTel: +44 (0) 20 3882 9621Email: vivet@optimumcomms.com 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 program VTX-PID, is aimed at depleting Neutralizing Antibodies (NAbs) levels for a given AAV serotype and is advancing in a Phase 1 dose escalating study in Nabs+ subjects. Its Leading pre-clinical program VTX-806, for the treatment of Cerebrotendinous Xanthomatosis (CTX), received ODD by the EC in September 2024 and is demonstrating its potential as an alternative treatment option for patients affected by the burden of CTX. 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 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 www.vivet-therapeutics.com - Follow us on LinkedIn @Vivet Therapeutics and Twitter @Vivet_tx…………………………

Seladelpar Treatment of PBC Patients for Two Years Predicts Improved Transplant-Free Survival NEWARK, Calif., June 22, 2022 (GLOBE NEWSWIRE) -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, today announced encouraging seladelpar data in patients with primary biliary cholangitis (PBC) that are being presented at The International Liver Congress™ 2022 of the European Association for the Study of Liver (EASL) which will be held in London, UK from June 22nd – 26th. In a poster presentation titled, “Seladelpar Treatment of Patients With Primary Biliary Cholangitis (PBC) For 2 Years Improves the GLOBE PBC Score and Predicts Improved Transplant-Free Survival,”1 Bettina Hansen, PhD, Associate Professor Toronto Centre for Liver Disease, University of Toronto, will be reporting the improvement in GLOBE score following seladelpar treatment over two years and predicted transplant-free survival. The GLOBE score is a validated risk-assessment tool providing an estimate of transplant-free survival for patients with PBC. Patients with PBC having an incomplete response or intolerance to UDCA (defined as alkaline phosphatase (ALP) ≥ 1.67xULN) had completed an open-label one-year phase 2 study of daily oral seladelpar therapy (NCT: 02955602). After 1 year, patients were eligible for an open label long-term study (NCT: 03301506). Treatment of 50 patients with oral seladelpar 5 mg or 10 mg daily for 2 years resulted in a mean (SD) change from baseline in GLOBE score of -0.417 (0.269), resulting in a corresponding hazard ratio of 0.66 for transplantation or death compared to no prior treatment with seladelpar (baseline). The improvement in GLOBE score and predicted survival did not depend on age. However, an analysis of subpopulations of high risk patients by GLOBE score (> 0.3) revealed that while patients of all ages improved, the younger patients tended to have numerically greater improvements, although these differences did not achieve significance. “These findings demonstrate that seladelpar treatment over 2 years resulted in a sustained decrease in GLOBE score for patients with PBC. These results provide an estimate of seladelpar’s treatment effect on transplant-free survival for patients with PBC supporting its continued long-term evaluation in patients with PBC,” said Dr. Bettina Hansen. An oral presentation2 by Dr. Bernd Schnabl, Professor of Medicine at the University of California San Diego, will describe the suppression of bile acid synthesis by seladelpar and reveal the role of FGF-21 signaling, a previously known regulator of bile acid synthesis. These results provide new insights into the anti-cholestatic mechanism of seladelpar. Dr. Dennis Kim, Chief Medical Officer of CymaBay Therapeutics, commented, “We continue to be encouraged by the potential key role seladelpar can play in providing benefit to patients with PBC. We look forward to our continued collaboratation with our academic partners and investigators to further explore how this first and only delpar in development for the treatment of PBC can advance the care and quality of life for patients with PBC over time. We want to extend our sincere gratitude to the patients and investigators who have participated in our clinical studies and look forward to completing our RESPONSE global Phase 3 study for seladelpar in PBC. Presentations at The International Liver Congress™ 2022 include: Poster Presentations: June 23rd 9:00 – 18:30 BST1529: 1“Seladelpar Treatment of Patients With Primary Biliary Cholangitis (PBC) For 2 Years Improves the GLOBE PBC Score and Predicts Improved Transplant-Free Survival”Bettina E. Hansen, Elaine Watkins, Ke Yang, Yun-Jung Choi, Charles A. McWherter, Gideon M. Hirschfield, for the Seladelpar Long-Term Study Investigators June 24th 9:00 – 18:00 BST1518: “Comparative fibrosis-reducing activities of farnesoid X receptor (FXR), peroxisome-proliferator activated receptor delta (PPAR) and thyroid hormone receptor (THR) agonists in the carbon tetrachloride mouse model” Edward Cable, Jeffrey Stebbins, Yun-Jung Choi, Jiangao Song, Prasad Manchem, Sanjay Pandey, Charles A. McWherter Oral Presentation: June 25th 9:00 AM BST2726: 2“The selective PPAR-delta agonist seladelpar suppresses bile acid synthesis by reducing hepatocyte CYP7A1 through the FGF21 pathway” Tetsuya Kouno, Xiao Liu, Tatiana Kisseleva, Edward E. Cable, Bernd Schnabl Congress attendees can visit CymaBay throughout the meeting at booth 93. A full list of presentations can be found on The International Liver Congress ™ 2022 website. The presentations will be made available on the CymaBay website. About PBCPBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000) over the age of 40. PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of alkaline phosphatase (ALP) and total bilirubin. The most common early symptoms of PBC are itching (pruritus) and fatigue, which can be very debilitating for some patients. Progression of PBC is associated with an increased risk of liver cancer and liver-related mortality. About SeladelparSeladelpar is a first-in-class oral, selective PPARδ agonist shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acids synthesis, inflammation, fibrosis and lipid metabolism, storage and transport. About CymaBayCymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need through a pipeline of innovative therapies. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, have helped us receive breakthrough therapy designation (U.S. Food and Drug Administration), PRIority MEdicines status (European Medicines Agency) and orphan drug status (U.S. and Europe) for seladelpar, a first-in-class treatment for people with primary biliary cholangitis (PBC). Our evidence-based decision-making and commitment to the highest quality standards reflect our relentless dedication to the people, families and communities we serve. To learn more, visit www.cymabay.com and follow us on Twitter and Linkedin. Cautionary StatementsAny statements made in this press release regarding the potential for seladelpar to treat PBC and potentially improve clinical symptoms of the disease and the potential benefits to patients are forward-looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of seladelpar could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, which include, without limitation, risks related to: the success, cost and timing of any of CymaBay's product development activities, including clinical trials; and effects observed in trials to date that may not be repeated in the future. Additional risks relating to CymaBay are contained in CymaBay's filings with the Securities and Exchange Commission, including without limitation its most recent Annual Report on Form 10-K, its Quarterly Reports on Form 10-Q and other documents subsequently filed with or furnished to the Securities and Exchange Commission. CymaBay disclaims any obligation to update these forward-looking statements except as required by law. For additional information about CymaBay visit www.cymabay.com. Public Relations Contact: Glenn SilverLazar-FINN Partners(973) 818-8198Glenn.silver@finnpartners.com Investor Relations Contact: Hans VitzthumLifeSci Advisors, LLC(617) 430-7578Hans@LifeSciAdvisors.com

NEWARK, Calif., June 08, 2022 (GLOBE NEWSWIRE) -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, today announced that multiple seladelpar presentations will be delivered during The International Liver Congress™ 2022 of the European Association for the Study of Liver (EASL) which will be held in London, UK from June 22nd – 26th. A poster presentation1 in collaboration with Dr. Bettina Hansen, PhD, Associate Professor of Biostatistics at the University of Toronto, Toronto, CA and Erasmus University Medical Center, Rotterdam, NL, will be made highlighting the improvement in GLOBE score following seladelpar treatment over two years and predicted transplant-free survival. The GLOBE score is a validated risk-assessment tool providing an estimate of transplant-free survival for patients with PBC.A preclinical poster presentation2 will compare the fibrosis-reducing activities of the Farnesoid X Receptor (FXR) agonist, obeticholic acid; the Peroxisome Proliferator-activated receptor delta (PPARd) agonist, seladelpar, and the Thyroid Hormone Receptor (THR) agonist, resmetirom in the carbon tetrachloride (CCl4) mouse model.An oral presentation3 in collaboration with Professor Bernd Schnabl at the University of California San Diego, will describe the suppression of bile acid synthesis by seladelpar and reveal the role of FGF-21 signaling, a previously known regulator of bile acid synthesis. Dr. Dennis Kim, Chief Medical Officer of CymaBay Therapeutics, commented, “We are excited to have the opportunity to present once again this year at the International Liver Congress™. We are honored to collaborate with our academic partners and investigators and to share clinical data that highlights the potential key role seladelpar can play in improving the lives of PBC patients.” Presentations at The International Liver Congress™ 2022 include: Poster Presentations: June 23rd 9:00 – 18:30 BST1529: 1“Seladelpar Treatment of Patients With Primary Biliary Cholangitis (PBC) For 2 Years Improves the GLOBE PBC Score and Predicts Improved Transplant-Free Survival”Bettina E. Hansen, Elaine Watkins, Ke Yang, Yun-Jung Choi, Charles A. McWherter, Gideon M. Hirschfield, for the Seladelpar Long-Term Study Investigators June 24th 9:00 – 18:00 BST1518:2“Comparative fibrosis-reducing activities of farnesoid X receptor (FXR), peroxisome-proliferator activated receptor delta (PPAR) and thyroid hormone receptor (THR) agonists in the carbon tetrachloride mouse model” Edward Cable, Jeffrey Stebbins, Yun-Jung Choi, Jiangao Song, Prasad Manchem, Sanjay Pandey, Charles A. McWherter Oral Presentation: June 25th 9:00 AM BST2726: 3“The selective PPAR-delta agonist seladelpar suppresses bile acid synthesis by reducing hepatocyte CYP7A1 through the FGF21 pathway” Tetsuya Kouno, Xiao Liu, Tatiana Kisseleva, Edward E. Cable, Bernd Schnabl Congress attendees can visit CymaBay throughout the meeting at booth 93. A full list of presentations can be found on The International Liver Congress ™ 2022 website. The presentations will also be made available later this month on the CymaBay website. About PBCPBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000) over the age of 40. PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of alkaline phosphatase (ALP) and total bilirubin. The most common early symptoms of PBC are itching (pruritus) and fatigue, which can be very debilitating for some patients. Progression of PBC is associated with an increased risk of liver cancer and liver-related mortality. About SeladelparSeladelpar is a first-in-class oral, selective PPARδ agonist shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acids synthesis, inflammation, fibrosis and lipid metabolism, storage and transport. About CymaBayCymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need through a pipeline of innovative therapies. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, have helped us receive breakthrough therapy designation (U.S. Food and Drug Administration), PRIority MEdicines status (European Medicines Agency) and orphan drug status (U.S. and Europe) for seladelpar, a first-in-class treatment for people with primary biliary cholangitis (PBC). Our evidence-based decision-making and commitment to the highest quality standards reflect our relentless dedication to the people, families and communities we serve. To learn more, visit www.cymabay.com and follow us on Twitter and Linkedin. Cautionary StatementsAny statements made in this press release regarding the potential for seladelpar to treat PBC and potentially improve clinical symptoms of the disease and the potential benefits to patients are forward-looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of seladelpar could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, which include, without limitation, risks related to: the success, cost and timing of any of CymaBay's product development activities, including clinical trials; and effects observed in trials to date that may not be repeated in the future. Additional risks relating to CymaBay are contained in CymaBay's filings with the Securities and Exchange Commission, including without limitation its most recent Annual Report on Form 10-K, its Quarterly Reports on Form 10-Q and other documents subsequently filed with or furnished to the Securities and Exchange Commission. CymaBay disclaims any obligation to update these forward-looking statements except as required by law. For additional information about CymaBay visit www.cymabay.com. Public Relations Contact: Glenn SilverLazar-FINN Partners(973) 818-8198Glenn.silver@finnpartners.com Investor Relations Contact: Hans VitzthumLifeSci Advisors, LLC(617) 430-7578Hans@LifeSciAdvisors.com