Metabolic Diseases

Visionary healthcare company adds obesity and chronic care management provider to its curated selection of market-tested services NEW CANAAN, Conn., Oct. 31, 2024 /PRNewswire/ -- Muse Health, a care navigation integrator of value-based benefits, has partnered with FlyteHealth to offer its members expert obesity care and chronic condition management. Muse Health's vertically integrated healthcare system is focused on an individual's whole health through interactions with healthcare providers in primary and specialty care. FlyteHealth delivers a comprehensive suite of clinical care, technology and support, reducing the complexity and cost of obesity and comorbid chronic conditions for employers and payers. As Muse Health and its clients identified the growing need for a new way to approach diabetes, hypertension and weight management, they conducted extensive market analysis and determined that FlyteHealth is the ideal partner to service its clients' employees/members. "The more complex the challenges encountered by our stakeholders, the more we require robust solutions. FlyteHealth's best-in-class medical obesity solution and their mission-focused management and operations team made them a perfect partner to optimize lifestyles around food and activity in a culturally concordant manner," said Muse Health CEO Ricardo Johnson II. "We are excited to work alongside FlyteHealth to accomplish this important work." Muse Health partners with payers, pharmacy benefit managers (PBMs), group employers, associations, and other entities to ensure that value-based benefits are cognizant of social determinants of health, racial equalities, gender fairness, and economic stabilization. The company identifies, assesses, and manages a suite of value-based benefit providers that align with its strategic, moral obligations. They also secure claims data from clients, leverage proprietary risk-stratification programs, and steer individuals (Medicare and Medicaid beneficiaries, labor and group employees) to its vendor partners for services. As its portfolio vendor partners deliver their services, Muse Health manages collaborative strategies between its clients and vendor partners to reach individuals where they live in the manner that works best for them. "We are delighted to be part of the Muse Health virtual care ecosystem," said FlyteHealth CEO and co-founder Sloan Saunders. "We like the unique market approach Muse Health is taking to ensure that all individuals, including the most disadvantaged ones, have access to quality healthcare." For more information, contact: Ricardo Johnson II, CEO, Muse Health, [email protected] Gabe Castaneda, Chief Revenue Officer, FlyteHealth, [email protected] About Muse Health Muse Health provides an integrated health solution to our healthcare partners, working exclusively with payers, providers, and service entities to provide transformative solutions focused on underrepresented populations. Muse Health focuses on an individual's whole health and their engagement with healthcare providers in primary, secondary, and tertiary care markets. MUSE HEALTH technology platform is present in over 100 hospital systems and over a dozen payer networks. For more information, please visit About FlyteHealth FlyteHealth is obesity care that empowers you. Delivering a comprehensive suite of clinical care, technology, and support, FlyteHealth reduces the complexity and cost of obesity and its comorbid conditions for employers and payers. Based on the founders' decades of research and clinical care, FlyteHealth clinicians deliver the latest in personalized medication therapy and behavior coaching. The evidence-based treatment protocols enable individuals not only to lose weight and maintain weight loss long-term, but also to achieve significant improvements in outcomes related to diabetes, hypertension, heart disease, and many other weight-related health complications. Through the Flyte Intelligence obesity treatment platform, FlyteHealth empowers healthcare providers with subject matter expertise and care navigation services. Drawing from the largest data set of obesity and chronic disease research, Flyte Intelligence enables delivery of the highest standard of patient care at scale. For more information, please visit . Contact: FlyteHealth Nicole Turgeon [email protected] (206) 295-2060 SOURCE FlyteHealth WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– Webcast to be Held at 8:00 am ET on November 7, 2024 – NEW YORK, Oct. 31, 2024 /PRNewswire/ -- Immunic, Inc. (Nasdaq: IMUX), a biotechnology company developing a clinical pipeline of orally administered, small molecule therapies for chronic inflammatory and autoimmune diseases, today announced that the company will release its financial results for the third quarter ended September 30, 2024, including a corporate update, on Thursday, November 7, 2024, before the opening of the U.S. financial markets. A webcast will follow at 8:00 am ET. To participate in the webcast, please register in advance at: or on the "Events and Presentations" section of Immunic's website at: ir.imux.com/events-and-presentations. Registrants will receive a confirmation email containing a link for online participation or a telephone number for dial in access. An archived replay of the webcast will be available approximately one hour after completion on Immunic's website at: ir.imux.com/events-and-presentations. About Immunic, Inc. Immunic, Inc. (Nasdaq: IMUX) is a biotechnology company developing a clinical pipeline of orally administered, small molecule therapies for chronic inflammatory and autoimmune diseases. The company's lead development program, vidofludimus calcium (IMU-838), is currently in phase 3 and phase 2 clinical trials for the treatment of relapsing and progressive multiple sclerosis, respectively, and has shown therapeutic activity in phase 2 clinical trials in patients suffering from relapsing-remitting multiple sclerosis, progressive multiple sclerosis and moderate-to-severe ulcerative colitis. Vidofludimus calcium combines neuroprotective effects, through its mechanism as a first-in-class nuclear receptor related 1 (Nurr1) activator, with additional anti-inflammatory and anti-viral effects, by selectively inhibiting the enzyme dihydroorotate dehydrogenase (DHODH). IMU-856, which targets the protein Sirtuin 6 (SIRT6), is intended to restore intestinal barrier function and regenerate bowel epithelium, which could potentially be applicable in numerous gastrointestinal diseases, such as celiac disease, for which it is currently in preparations for a phase 2 clinical trial. IMU-381, which currently is in preclinical testing, is a next generation molecule being developed to specifically address the needs of gastrointestinal diseases. For further information, please visit: . Cautionary Statement Regarding Forward-Looking Statements This press release contains "forward-looking statements" that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, future financial position, future revenue, projected expenses, sufficiency of cash and cash runway, expected timing, development and results of clinical trials, prospects, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to Immunic's development programs and the targeted diseases; the potential for Immunic's development programs to safely and effectively target diseases; preclinical and clinical data for Immunic's development programs; the timing of current and future clinical trials and anticipated clinical milestones; the nature, strategy and focus of the company and further updates with respect thereto; the development and commercial potential of any product candidates of the company; and the company's expected cash runway. Immunic may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Such statements are based on management's current expectations and involve substantial risks and uncertainties. Actual results and performance could differ materially from those projected in the forward-looking statements as a result of many factors, including, without limitation, the COVID-19 pandemic, increasing inflation, impacts of the Ukraine – Russia conflict and the conflict in the Middle East on planned and ongoing clinical trials, risks and uncertainties associated with the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the availability of sufficient financial and other resources to meet business objectives and operational requirements, including the ability to satisfy the minimum average price and trading volume conditions required to receive funding in tranche 2 and 3 of the January 2024 private placement, the fact that the results of earlier preclinical studies and clinical trials may not be predictive of future clinical trial results, the protection and market exclusivity provided by Immunic's intellectual property, risks related to the drug development and the regulatory approval process and the impact of competitive products and technological changes. A further list and descriptions of these risks, uncertainties and other factors can be found in the section captioned "Risk Factors," in the company's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, filed with the SEC on February 22, 2024, and in the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at or ir.imux.com/sec-filings. Any forward-looking statement made in this release speaks only as of the date of this release. Immunic disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances that exist after the date on which they were made. Immunic expressly disclaims all liability in respect to actions taken or not taken based on any or all the contents of this press release. Contact Information Immunic, Inc. Jessica Breu Vice President Investor Relations and Communications +49 89 2080 477 09 [email protected] US IR Contact Rx Communications Group Paula Schwartz +1 917 633 7790 [email protected] US Media Contact KCSA Strategic Communications Caitlin Kasunich +1 212 896 1241 [email protected] SOURCE Immunic, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

文章信息 文章题目 Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch 期刊 Cell 发表时间 2024年10月29日 主要内容 北京大学雷晓光课题组联合北京大学李毓龙课题组，及北京佑安医院陈煜课题组，在Cell杂志上发表了文章Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch，该研究系统地揭示了人体内源“天然产物”分子胆酸诱导胆汁淤积瘙痒的分子机制，并且开发出针对多种肝胆疾病具有良好治疗效果且不存在瘙痒副作用的先导药物分子。 原文链接 https://doi-org.libproxy1.nus.edu.sg/10.1016/j.cell.2024.10.001 使用TransGen产品 TransStart®FastPfu DNA Polymerase (AP221) 研究背景 瘙痒自古以来一直被人们所关注，现代医学已表明，组胺依赖的急性瘙痒，如过敏或蚊虫叮咬等，可通过抗组胺类药物有效缓解。然而，非组胺依赖的全身性慢性瘙痒却无法通过这种药物进行治疗，因此困扰了大量慢性瘙痒患者。 胆酸在人体中具有至关重要的生理功能，主要参与脂肪的消化吸收和胆固醇的代谢调节。胆酸通过肠肝循环不断再利用，维持着机体的代谢平衡。然而，当胆汁流动受阻，发生胆汁淤积时，胆酸无法正常代谢并在体内积累，导致约80%的胆汁淤积患者出现严重的慢性瘙痒，极大地影响他们的生活质量。迄今为止，导致胆汁淤积瘙痒的分子机制仍不明确，且缺乏有效的治疗药物。 文章概述 首先，该研究团队收集到数十例有瘙痒症状或无明显瘙痒症状的胆汁淤积病人血浆样本。通过分析这些样本发现在伴有瘙痒症状的胆汁淤积患者中，一种包含了特殊修饰的3位羟基磺酸化胆酸（BA-3S）含量显著增高，磺酸化修饰的胆酸很可能也与胆汁淤积病人的瘙痒症状有着密切的联系，有望用于预测和监测瘙痒的发生。那么，磺酸化修饰后的胆酸是如何导致胆汁淤积病人产生瘙痒症状的呢？ 接下来，研究者针对这一分子机制展开了详细的研究。研究者怀疑，是不是磺酸化后的胆酸对于hX4具有更强的亲和力，从而产生这种更为严重的瘙痒现象。为了证明这一点，研究者测试了不同修饰类型的胆酸对于hX4的激活活性，结果表明胆酸的3号位羟基（3-OH）对于激活hX4具有非常重要的作用，其被磺酸化修饰后显著提高了亲和力，被氧化后则显著降低了激活活性。接着，研究者发现DCA和DCA-3S这两种胆酸都能够导致人源化大鼠产生瘙痒症状，并且DCA-3S能够产生更为严重的瘙痒。那么磺酸化修饰是如何增强胆酸对于hX4的亲和力的呢？ 研究者推测磺酸化胆酸活性的提高可能与磺酸基团携带了一个负电荷有关。研究者通过人工合成的3位磷酸化修饰胆酸DCA-3P成功解析了胆酸类化合物与hX4的复合物结构，首次揭示了胆酸是如何激活hX4的分子机制。 正如所预测的那样，DCA-3P的磷酸部分（P-Head）被锁定在富含正电氨基酸的结合腔中，这种静电相互作用正是导致磺酸化和磷酸化胆酸激活活性提升的主要原因。此外，研究者也发现，DCA-3P中部的疏水部分（H-Middle）通过疏水相互作用被hX4中间丰富的疏水氨基酸所稳定。这些研究详细阐明了胆酸激活hX4的分子机制，展示了3-OH基团和磺酸化修饰在激活hX4过程中发挥的关键作用，为我们理解胆酸诱发瘙痒提供了全新视角。 随后研究者也同时关注到现有临床药物奥贝胆酸（OCA）在治疗过程中的瘙痒副作用，推测OCA产生瘙痒的副作用可能也是通过激活hX4来实现的。进一步通过分子、动物、人体等多方位的角度证实，OCA确实可以激活hX4并且在人源化大鼠模型，甚至人体上产生剂量依赖性的瘙痒症状。因此，OCA导致瘙痒副作用的靶点确实就是hX4。 为了研究C7的全基因组效应，研究人员对C7和OCA处理后的HepG2细胞进行了RNA测序分析。结果证实了C7在治疗NASH等肝脏疾病方面依然具备显著疗效，且不会引发瘙痒问题。进一步研究发现，C7在胆汁淤积和非酒精性脂肪性肝炎（NASH）模型中展现出强大的肝保护作用和抗纤维化潜力，其有望成为治疗胆汁淤积和NASH等肝病的创新药物。 综上所述，该研究工作围绕胆汁淤积瘙痒和肝病治疗新策略两个方面展开了非常系统的研究。第一个方面，从临床样本出发，结合高分辨质谱发现3位羟基磺酸化修饰胆酸在瘙痒胆汁淤积病人体内显著升高，它们能够通过增强对于hX4的激活活性从而导致更为严重的瘙痒症状。此外，利用冷冻电镜技术，解析了hX4与胆酸类似物的复合物结构，详细地阐明了胆酸的3-OH对于激活hX4的重要作用。第二个方面，研究者针对OCA在临床上导致瘙痒副作用开展了一系列的机制和分子改造研究。首先证实OCA通过激活hX4导致瘙痒副作用，接着根据发现的胆酸激活hX4的分子机制，精准地对OCA进行化学改造，成功地获得了失去瘙痒副作用，并且保留了肝病治疗活性的新一代药物分子C7，为临床肝病治疗提供了全新的可能性，有望彻底解决OCA在临床上应用中遇到的瘙痒难题。 全式金产品支撑 优质的试剂是科学研究的利器。全式金生物的PCR产品 TransStart®FastPfu DNA Polymerase (AP221) 助力本研究。 TransStart®FastPfu DNA Polymerase (AP221)  本产品是用于快速 PCR 的热启动高保真 DNA 聚合酶，其扩增效率高、扩增速度快 (4 kb/min，是普通 Pfu 酶的 8 倍)，克服了普通 Pfu 酶扩增效率低、产量低和扩增速度慢 (0.5 kb/min) 的缺陷，极大地缩短了反应时间，自上市以来多次荣登 Cell、Nature 等知名期刊，助力科学研究。 产品特点 快速：4 kb/min 的延伸速度 高保真性：保真性为普通 Taq 酶的 54 倍，普通 Pfu 酶的 3 倍 长片段扩增：基因组 DNA 片段的扩增可达 15 kb，Plasmid DNA 片段的扩增可达 20 kb 高特异性：采用“TransStart” 双封闭法新型热启动技术，同时封闭引物和模板 扩增能力强：独有的 PCR Stimulant，提升该酶对复杂模板的扩增能力 扩增产物为平端，可直接克隆于 pEASY®-Blunt 系列载体中 数据展示 使用 TransStart®FastPfu DNA Polymerase  (AP221) 产品发表的部分文章： • Yang J, Zhao T J, Fan J P, et al. Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch [J]. Cell, 2024. • Wang Y,  Zhang S, Yang X, et al. Mesoscale DNA feature in antibody-coding sequence facilitates somatic hypermutation[J]. Cell, 2023. • Zhang H, Zhu Y, Liu Z, et al. A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness[J]. Cell,2022. • Lei Z, Meng H, Liu L, et al. Mitochondrial base editor induces substantial nuclear off-target mutations[J]. Nature, 2022. • Chen J, Ou Y, Yang Y, et al. KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing[J]. Nature, 2018 • Fan J, Ran H, Wei P L, et al. Pretrichodermamide A Biosynthesis Reveals the Hidden Diversity of Epidithiodiketopiperazines[J]. Angewandte Chemie, 2023. • Song Z, Zhou S, Zhang H, et al. Fungal secondary metabolism is governed by an RNA-binding protein CsdA/RsdA complex[J]. Nature Communications, 2023. • Lei Y, Fei P, Song B, et al. A loosened gating mechanism of RIG-I leads to autoimmune disorders[J]. Nucleic acids research, 2022. • Zhang H, Li Z, Zhou S, et al. A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin[J]. Nature Communications, 2022. • Li Y, Zhao L, Zhang Y, et al. Structural basis for product specificities of MLL family methyltransferases[J]. Molecular Cell, 2022. 全式金生物产品再一次登上 Cell 期刊，证明了大家对全式金生物产品品质和实力的认可，也完美诠释了全式金生物一直以来秉承的“品质高于一切，精品服务客户”的理念。全式金生物始终在助力科研的道路上砥砺前行，希望未来能与更多的科研工作者并肩奋斗，用更多更好的产品持续助力科研。