Novartis

1月7日，上海阿尔戈生物制药有限公司（“Argo”），一家专注于发现和开发下一代RNAi疗法的生物技术公司，宣布已与诺华PHARMA AG（“诺华”）签订了两项独家许可和合作协议。​ 1. Argo授予了诺华独家全球许可证，以开发和商业化第一阶段计划。该协议包括一项研究合作，Argo授予诺华独家前大华许可证，以开发和商业化心血管疾病治疗的1/2a阶段临床阶段计划。1阶段心血管资产的全球独家许可，以及针对最多两个心血管目标的化合物许可选项。Argo将对其选择进行发现和优化，以交付PCC，届时诺华将可获得全球独家许可。 2. Argo将从诺华公司获得1.85亿美元的预付款，并有资格获得潜在的期权和里程碑付款以及商业销售的分级版税。Argo和分级版税的合并潜在价值高达41.65亿美元。 这些项目使用Argo的先进RNA干扰（RNAi）技术发现和开发，将加强和扩大Novartis RNAi关于心血管和代谢疾病（CVM）的投资组合。 这些临床阶段资产使用Argo的尖端RNAi平台技术发现和开发，提供行业领先的疗效和耐久性疗法。 “这是中国生物技术公司在RNAi领域的首笔重大海外许可交易。我们很高兴心血管疾病和RNAi治疗的全球领导者诺华认识到Argo团队在过去两年中通过先进的RNAi平台技术和新一代CVM管道创造的巨大价值。”Argo Biopharma总裁兼首席执行官Dongxu Shu说。诺华在CVM中经过验证的开发能力、全球商业影响力和广泛的经验使其成为加速开发我们的候选药物并将这些药物带给患者的理想合作伙伴。 诺华心血管和代谢疾病领域研究负责人Shaun Coughlin说，我们相信Argo使用其最先进的RNAi平台开发的心血管项目是对诺华基于RNA的治疗管道的补充。我们期待与Argo合作，推进这些研究性疗法，以帮助解决心血管医学中未满足的患者需求。 Argo成立于2021年4月，是一家总部位于上海的私营生物技术公司。该公司的主要重点是RNAi药物的研发。Argo开发了行业领先的RNAi平台技术，名为RADS（具有卓越活性、持续时间和安全性的RNAi分子），体现了Argo在交付、化学改性和序列设计方面的技术能力，持续产生顶级RNAi疗法。 Argo目前的管道包括20多个治疗心血管和代谢疾病、血液学、补体途径疾病、病毒感染和神经退行性疾病的治疗项目。五个领先的项目都处于临床开发阶段，都表现出了良好的耐受性安全状况和一流的潜力。​

MELBOURNE, Australia, Oct. 28, 2024 (GLOBE NEWSWIRE) -- Aravax, a clinical-stage biotechnology company developing next-generation immunotherapies designed to be safe, convenient, and precisely targeted, today announces it has completed patient recruitment into its Phase 2 study (AVX-201) of its novel, precision therapy PVX108 for the treatment of peanut allergy. Aravax’s PVX108 is an advanced immunotherapy designed to ‘re-train’ the immune system by administering engineered peptides to precisely target T cells and reverse the course of allergic disease. Unlike most treatments available, or under development for peanut allergy, PVX108 does not contain peanut proteins which put patients at significant risk of serious side effects, which leads to complex and burdensome dosing regimens. The study, which is being conducted under an U.S. FDA Investigational New Drug Application, has enrolled 95 patients across eight trial sites in the U.S. and six in Australia. Trial participants were children and adolescents aged four to 17 years with peanut allergy. The trial is a double-blind, placebo-controlled study designed to evaluate the safety and efficacy of two dose levels of PVX108 versus placebo, administered monthly for one year. In Phase 1 trials, researchers observed that PVX108 produced relevant changes in the immune response to peanut protein, which continued to develop once dosing had completed. The primary endpoint of this Phase 2 study is ratio of maximum tolerated dose of peanut protein in a controlled food challenge at the end of the study period relative to baseline. Headline results are expected in H1 2026. Dr Pascal Hickey, CEO of Aravax, said: “The timely completion of recruitment across multiple sites in the U.S. and Australia, is a significant step for Aravax. There remains a critical need for better treatments for serious food allergies. PVX108 has been designed to provide a safe and convenient treatment which has the potential to reverse the course of allergic disease. We look forward to continuing evaluation of PVX108 efficacy in this potentially Phase 3-enabling study.” About Aravax Aravax is a clinical stage biotechnology company focused on revolutionising the treatment of food allergies with next-generation specific immunotherapies which are safe, effective and convenient. Aravax applies proprietary technology and know-how to design highly targeted immunotherapies, which reset the immune system to tolerate a specific allergen without evoking allergic reactions during treatment. The lead product, PVX108, is being developed for the treatment of peanut allergy. Founded in 2015 based on technology from Alfred Health and Monash University, Aravax is a private company headquartered in Melbourne. Its investors include Brandon Capital, Tenmile, Novartis Venture Fund, Breakthrough Victoria, Uniseed, UniSuper and Agati Capital. For more information visit: www.aravax.com.au About PVX108 PVX108 is an innovative precision immunotherapy containing a mixture of synthetic peptides which are designed to precisely target the T cells which drive peanut allergy. Each peptide represents a dominant T cell epitope from major peanut allergens. PVX108 does not contain natural extracts or whole allergens and has been engineered to be incapable of triggering acute allergic reactions. It has been designed to provide a safe, convenient and long-lasting treatment with monthly dosing through essentially needle-free intradermal administration. Media – Australia Kirrily Davis, E: kdavis@bcpvc.com M: +61 (0)401 220228 Media – International Sue Charles, Charles Consultants E: sue.charles@charles-consultants.com M: +44 (0)7968 726585

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…………………………