CYP27A1

Funding from French Government as part of the France Health Innovation Plan 2030 operated by Bpifrance PARIS, Feb. 1, 2024 /PRNewswire/ -- Vivet Therapeutics ("Vivet"), a clinical stage biotech company developing novel and long-lasting gene therapies for rare inherited metabolic disorders, announces the financing of EUR 4.9 million received from the French government to advance the development of a gene therapy for the treatment of cerebrotendinous xanthomatosis (CTX), a rare neurodegenerative disease. This funding is from the "Innovations in biotherapies" framework of the France Health Innovation Plan 2030 and specifically the acceleration strategy Biotherapies – Bioproduction in innovative therapies. Coordinated by the French Health Innovation agency, the funding, will be distributed over a three-year period and operated by Bpifrance. CTX is a rare autosomal recessive genetic disorder that affects the body's ability to metabolize fats known as cholesterols. Patients with CTX are unable to break down different forms of cholesterol, which build up in certain areas of the body and are characterized by fatty yellow nodules (tendon xanthomas) located in the connective tissues within the brain. These deposits can cause progressive damage to the brain and other areas of the body. Disease symptomatology is characterized by chronic diarrhea during infancy and cataracts in late childhood. When patients enter adulthood, they begin to demonstrate progressive neurological symptoms, which may include dementia, seizures, hallucinations, depression and difficulty with coordination and speech. At present there is no cure for CTX, only treatment to slow disease progression. Vivet will use the funds to further develop its gene therapy product VTX-806 as an effective treatment option to stop or reverse disease progression over the long-term, or potentially cure CTX in patients. By reinstating the CYP27A1 gene activity, which is impaired in CTX patients, using an adeno-associated viruses (AAV) vector, Vivet aims to demonstrate a safe and feasible treatment option for CTX disease. Gloria Gonzalez, Chief Scientific Officer at Vivet Therapeutics, said: "Our commitment to developing treatment options for metabolic disorders is demonstrated by our lead clinical program, VTX-801 which targets Wilson Disease, alongside a second program, VTX-806, which is in development as a potential treatment option for CTX patients. Our advanced pipeline highlights our ability to provide strong translational support for rare genetic disorders and patients' needs, notably with the help of the CTX Alliance and the Spanish CTX patient association." Anne Douar, Chief Operating Officer at Vivet Therapeutics, commented: "CTX is a progressive, neurodegenerative disorder, that if left untreated can lead to debilitating consequences and a poor prognosis effecting a patient's lifespan. The funding granted as part of France Health Innovation Plan 2030 will enable Vivet to accelerate the development of a transformative and potentially curative treatment with our gene therapy product VTX-806 for patients with CTX." The funding is for the CrisTauX program which will cover preclinical research and development activities of VTX-806 and includes the manufacturing process development within medicine good manufacturing practices rules and a clinical study aiming at identifying biomarkers for the effectiveness of treatment in patients under standard of care. CrisTauX will enable accelerated clinical development of VTX-806 upon completion of the program. 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. For more information, please visit - Follow us on LinkedIn @Vivet Therapeutics and Twitter @Vivettherapeutics About France 2030 Translates a double ambition: to transform key sectors of our economy (energy, automotive, health, aeronautics, space) through technological and industrial innovation, and to position France not only as a participant but as a leader in the world of tomorrow. From fundamental research and the emergence of an idea to the production of a new product or service, France 2030 supports the entire life cycle of innovation until its industrialization. Is unprecedented in its scale: 54 billion euros will be invested so that our companies, universities, and research organizations can successfully transition in these strategic sectors. The goal: to allow them to respond competitively to environmental challenges and attractiveness of the world to come, and to emerge as future champions in our fields of excellence, thus strengthening French sovereignty and independence in key sectors. 50% of the expenses will be dedicated to decarbonizing the economy, and 50% will be directed towards emerging actors who are driving innovation without negatively impacting the environment (according to the principle of Do No Significant Harm). Will be implemented collectively: the plan is thought out and deployed in consultation with economic, academic, local, and European actors who have contributed to determining strategic orientations and flagship actions. Project leaders are invited to submit their applications through open, demanding, and selective procedures to benefit from support from the State. Is led by the General Secretariat for Investment on behalf of the Prime Minister and implemented by the Agency for Ecological Transition (ADEME), the National Research Agency (ANR), Bpifrance and the Caisse des Dépôts et Consignations (CDC). More information on: france2030.gouv.fr | | @SGPI_avenir About - Bpifrance Bpifrance finances companies at every stage of their development with credit, guarantees and equity. Bpifrance supports them in their innovation and international projects and now also insures their export business through a wide range of products. Consulting, training, networking and acceleration programs for start-ups, SMEs and mid-sized companies are some of the other services it offers to entrepreneurs. Thanks to Bpifrance and its 50 regional offices, entrepreneurs have a single local contact to help them through the challenges they face. For more information, visit – Follow us on Twitter: @Bpifrance - @BpifrancePresse 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

BUDAPEST, Hungary I January 16, 2024 I VRG Therapeutics Plc. announces successful in vivo efficacy results of their CAR-T project with patented chlorotoxin analogue targeting glioblastoma, encouraging further development. VRG Therapeutics (VRG Tx), a biotechnology R&D company focused on miniprotein pharmaceuticals and cellular & gene therapy (CGT) products has announced that their proprietary chlorotoxin (CTX) analogue, CTXA8, applied as a targeting molecule in chimeric antigen receptor T (CAR-T) cells, shows efficacy in an in vivo heterotopic glioblastoma murine model. CTXA8 has been developed leveraging VRG Tx’s AI-powered miniprotein platform. The promising preclinical results give a solid background to speed up the allogenic gamma-delta CAR-T (γδCAR-T) program. The company is committed to proceed with the project towards clinical development and is looking for a co-development partner with expertise in CAR-T preclinical and clinical development. CAR-T therapy targeting brain tumors: CAR-T cells are modified white blood cells expressing a chimeric antigen receptor (CAR) against a specific tumor antigen that holds the potential of identification and elimination of cancer cells. The extraordinary therapeutic effect experienced with CAR-T cell therapies targeting hematological malignancies have drawn interest in developing similar products for solid tumors, including brain tumors. High overexpression of MMP2 protein on tumor cells is a recently utilized new target in CAR-T therapy in glioblastoma. The expected increased safety and efficacy of CTXA8-based CAR-T therapy can be explained by the enhanced affinity and selectivity of CTXA8 versus original CTX towards MMP2 overexpressing tumors, such as glioblastoma. VRG Tx’s animal in vivo proof of concept (PoC) study: VRG Tx established a heterotopic xenograft mice model to demonstrate the effectiveness and safety of its CTXA8-targeting CAR-T cell therapy that is designed to treat patients with glioblastoma multiforme (a common type of brain tumor). The mouse model closely mirrors the clinical trial that is currently ongoing with CAR-T cells targeting the original CTX (NCT04214392, City of Hope Medical Center). CTXA8-CAR-T cells showed effective tumor growth inhibition compared to non-specific T cell controls at three different dose levels. The highest dose of administered CTXA8-CAR-T resulted in over 60% inhibition of tumor growth including two individuals with complete tumor remission. The animals did not show any signs of toxicity or body weight loss during the study indicating promising safety features. VRG Tx’s allogenic CAR-T therapy targeting brain tumors: VRG Tx is currently looking for a co-development partner experienced in allogenic CAR-T development, to step into preclinical phase with its proprietary CTXA8 analogue applied in allogenic cell therapy applications. Based on the same MoA, in vitro results of VRG Tx’s CTXA8- γδCAR-T cells show efficacy and high durability against glioblastoma multiforme cells. About VRG Tx’s Miniprotein platform utilizing ISEP and WISDOM technologies: VRG Tx’s proprietary miniprotein technology leverages artificial intelligence (AI) and pioneers in protein engineering to create CGT and peptide-based applications. The Wetlab-verified In Silico Design of Miniproteins (WISDOM) and Individual Sequence Enrichment Pattern (ISEP) technologies build on the evolutionary conserved structures of natural peptides and applies both in silico and in vitro high throughput screenings. Combining AI-powered interaction modelling with NGS-based advanced analytics, VRG Tx designs novel therapeutic candidates with unprecedented selectivity and affinity in an extremely fast discovery process. Miniproteins combine the benefits of small molecules and biologics. About VRG Tx: VRG Therapeutics is an original biopharmaceutical research and development company located in Budapest, Hungary. VRG Tx’s vision is to leverage its unique miniprotein ISEP and WISDOM technologies to create cure for diseases through targets and mechanisms of action that are beyond the reach of conventional biopharma approaches. For more information, please visit www.vrgtherapeutics.com . SOURCE: VRG Therapeutics