KCNN4

PRESS RELEASE November 3, 2022 SAN903 has finalized preclinical development and fulfilled other requirements for clinical developmentPotential first-in-class compound offers a new treatment paradigm for inflammatory and fibrotic diseases Saniona (OMX: SANION), a clinical stage biopharmaceutical company, today announced that SAN903 is ready to start the regulatory process for entering Phase 1 clinical trials either by Saniona alone or together with a partner following successful completion of preclinical development. “Preclinical data for SAN903 are very compelling and we believe it has potential to become first-line treatment in patients suffering from inflammatory bowel disease, IBD, where it could be the first maintenance drug with independent actions on both acute inflammation and chronic fibrotic complications. Other potential indications include fibrotic disorders such as chronic kidney disease, CKD, and the fatal lung disease idiopathic pulmonary fibrosis, IPF. There is a significant unmet medical need and commercial opportunities in inflammatory bowel disease and rare fibrotic disorders,” said Thomas Feldthus, Chief Executive Officer of Saniona. SAN903 is a novel, potential first-in-class medicine based on inhibition of the calcium-activated potassium ion channel, KCa3.1. This ion channel is found on several types of immune cells, where it participates in the control of the cellular pathways that maintain pathogenic activation and inflammation in chronic diseases. The KCa3.1 channel is also expressed on fibroblasts, especially on myofibroblasts, where it supports the overproduction of connective tissue that can lead to fibrosis. Prevention of fibrotic complications is an aspect of the disease, which is poorly treated by current standard-of-care IBD medicines, and progressed fibrosis often requires surgical intervention to resolve potentially life-threatening gut obstructions. SAN903 dampens inflammation and fibrosis by preventing cell division and cell migration of activated immune cells and fibroblast and by impeding cytokine release and collagen secretion of the respective cell types. Palle Christophersen, EVP Research, commented: I am incredibly happy that SAN903 – which is the result of a long and challenging drug discovery phase – has now successfully completed the preclinical development package and is ready for entering the clinical stages. Inflammatory bowel disease is a complex disease with a rather low initial responder rate and poorly controlled disease progression. Due to its new mode-of-action, I anticipate that the entry indication for SAN903 can be newly diagnosed, mild-to-moderate colitis patients that are failing first-line treatment with standard-of-care medicine. Due to the actions on both inflammatory and fibrotic processes, I hope that SAN903 can become the first maintenance drug, which effectively prevents development of intestinal fibrosis in patients suffering from inflammatory bowel disease. For more information, please contact Thomas Feldthus, CEO, +45 22109957; thomas.feldthus@saniona.com This information is such information as Saniona AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. This information was submitted for publication, through the agency of the contact person set out above, at 08.00 CET on 3 November 2022. About Saniona Saniona is a clinical-stage biopharmaceutical company focused on the discovery and development of medicines modulating ion channels. The company’s most advanced product candidate, Tesomet™, has been progressed to mid-stage clinical trials for rare eating disorders. Through its ion channel expertise, Saniona is advancing two product candidates, SAN711and SAN903. SAN711 has successfully completed a Phase 1 clinical trial for the treatment of neuropathic pain conditions. SAN903 is ready for Phase 1 clinical studies for the treatment of inflammatory and fibrotic disorders. The company has research and development partnerships with Boehringer Ingelheim GmbH, Productos Medix, S.A de S.V and Cephagenix ApS. Saniona is based in Copenhagen, Denmark, and listed on Nasdaq Stockholm Small Cap (OMX: SANION). Read more at http://www.saniona.com. About inflammatory bowel diseases It is estimated that 2.5 million patients are diagnosed with IBD (1 million colitis and 1.5 million Crohn’s patients) in the seven major markets (USA, Japan; 5 major EU countries). The incidences are increasing, especially in newly industrialized countries, presumably due to changes in lifestyle. Currently used anti-IBD drugs are anti-inflammatory (5-ASA´s, steroids, JAK inhibitors), generally immune dampening (azathioprine, 6-mercaptopurine), or biological single cytokine/integrin neutralizing agents (e.g. infliximab, ustekinomab, vedolizumab). Despite these options and carefully optimized clinical procedures, patients still face rounds of gut-shortening surgeries (many Crohn’s patients experience at least one surgery in their lifetime), and colitis patients may develop proctitis after colectomy. Suboptimal medical disease control with respect to maintaining long-term remission, to fight flare ups, and especially avoiding development of irreversible structural changes due to irresolvable gut fibrosis, represents a serious unmet need for IBD patients. Attachment 20221103 Saniona SAN903 (UK)

BOSTON and SEONGNAM, South Korea, Sept. 1, 2022 /PRNewswire/ -- Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotechnology company focused on developing novel drugs for cancer, fibrosis and inflammation, presented the non-clinical study results of 'BBT-301', a novel, small molecular inhibitor of KCa 3.1, and 'BBT-209', an endogenous GPCR19 agonist, both being developed as novel IPF treatments, at the 6th Annual IPF Summit (August 29 - September 1, 2022), in Boston, MA. During the poster presentation titled "BBT-301: a potent KCa3.1 modulator in development to treat idiopathic pulmonary fibrosis", the company highlighted the potent anti-fibrotic efficacy of BBT-301, observed through cell-based biochemistry assays and animal model studies. BBT-301 inhibits KCa 3.1, a calcium-activated potassium channel at an IC50 (inhibitory concentration 50%) of 6nM, which suggests a competitive channel inhibitory efficacy in the same class of candidates. BBT-301 also improved pulmonary function, and attenuated Ashcroft and collagen deposition in bleomycin (BLM)-induced animal model. According to the in-vivo data exhibited at the poster presentation, BBT-301 inhibited the expression of collagen in a dose-dependent manner. In terms of forced vital capacity (FVC) and pressure-volume curve, BBT-301 has also shown comparable potency in lung function recovery compared to the current standard of care (SoC). In addition to BBT-301, the company unveiled non-clinical data of BBT-209, under the title of "BBT-209: endogenous GPCR19 agonist attenuates animal model of idiopathic pulmonary fibrosis". According to the poster presentation, BBT-209 has exhibited competitive inhibitory effects against cytokine expressions such as IL-1β and TNF-α, with EC50 (effective concentration of 50%) of 0.031 and 0.36 μM each. Through the cell-based biochemistry assay and the BLM mouse model, BBT-209 also exhibited a strong anti-inflammatory effect reaching over 80%, and inhibitory efficacy of α-SMA (α-smooth muscle actin) expression, which is suggestive of combination therapies with the current standard of care and novel IPF treatments with strong anti-fibrotic drugs such as BBT-877, which is being developed as a potent best-in-class autotaxin inhibitor. "We are excited to present the non-clinical data of BBT-301 and BBT-209, our new assets being developed for the treatment of IPF," said James Lee, founder and CEO of Bridge Biotherapeutics. "In addition to our commitment to develop novel treatment options with therapeutic benefits, we will continue to enhance our pipeline to address the significant unmet needs in IPF, a serious disease caused by various factors." Posters presented at the conference is available at: https://bit.ly/3CPAxmS. About Bridge Biotherapeutics, Inc. Bridge Biotherapeutics Inc., based in the Republic of Korea, US, and China, is a publicly-traded, clinical-stage biotech company founded in 2015. Bridge Biotherapeutics is engaged in the discovery and development of novel therapeutics, focusing on therapeutic areas with high unmet needs including ulcerative colitis, fibrotic diseases, and cancers. The company is developing BBT-401, a first-in-class Pellino-1 inhibitor for the treatment of ulcerative colitis, BBT-877, a novel autotaxin inhibitor for the treatment of fibrotic diseases including idiopathic pulmonary fibrosis (IPF), and BBT-176, a potent targeted cancer therapy for non-small cell lung cancer (NSCLC) with C797S triple EGFR mutations. SOURCE Bridge Biotherapeutics, Inc.

▎药明康德内容团队编辑阿尔茨海默病是老年人中最常见的神经退行性疾病，以往研究显示，大脑中的小胶质细胞在神经免疫和阿尔茨海默病发病过程中起到关键的作用。然而，科学家对调节小胶质细胞功能的遗传调控网络，以及它们如何影响阿尔茨海默病所知有限。一个原因是以前的研究是基于对动物模型或者细胞系模型的研究，这些模型未能真正反映小胶质细胞在人类大脑中的复杂功能。近日，纽约西奈山医学院（Mount Sinai School of Medicine）的研究人员对人类小胶质细胞进行了分子生物学分析，发现了21个与阿尔茨海默病风险相关的基因位点。研究人员从150名捐献者中获取了新鲜大脑组织，他们包括阿尔茨海默病患者和未患病的老人。从中采集了高质量的小胶质细胞，并且利用RNA测序等多种方法对小胶质细胞的转录组和染色质可及性状态进行了分析。获得了与基因表达、表观遗传学调控和基因突变相关的多重信息。他们的分析结果找到了基因组中与阿尔茨海默病风险相关的21个基因位点。其中，一个名为SPI1的基因是调节小胶质细胞基因表达的关键转录因子，并且与阿尔茨海默病的风险有密切联系。此外，研究人员还发现3个新的潜在风险基因（KCNN4，FIBP和LRRC25）。▲这项研究的流程（图片来源：参考资料[2]）“我们的研究是迄今为止，针对阿尔茨海默病遗传风险因子最大规模的人类新鲜组织小胶质细胞分析。”文章的资深作者，西奈山医学院的Panos Roussos博士说，“通过更好地了解与小胶质细胞功能相关的分子和遗传机制，我们能够更好地揭开阿尔茨海默病的机理，从而为开发创新疗法铺平道路。”药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息参考资料：[1] Researchers gain insights into the genetic and molecular machinery that predisposes individuals to Alzheimer's disease. Retrieved August 12, 2022, from https://www.sciencedaily.com/releases/2022/08/220805154359.htm[2] Kosoy et al., (2022). Genetics of the human microglia regulome refines Alzheimer’s disease risk loci. Nature Genetics，https://doi.org/10.1038/s41588-022-01149-1免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新