Hong Kong Baptist University

HONG KONG, Sept. 4, 2024 /PRNewswire/ -- The Centre for Chinese Herbal Medicine Drug Development (CDD) at Hong Kong Baptist University (HKBU) has achieved a significant milestone in developing a novel Chinese herbal formulation for ulcerative colitis remission maintenance. Following a submission of Investigational New Drug application for CDD-2103 to the National Medical Products Administration (NMPA) in mid-June this year, CDD has received in late August its authorisation for clinical trial. Continue Reading (From right) Ms Emily Au, Assistant Director (Research and Development); Dr Tan Hor Yue, Assistant Professor; and Mr Duan Zhigang, Senior Regulatory Affairs Manager of CDD at HKBU, introduce the development of the novel Chinese herbal formulation for ulcerative colitis remission maintenance. CDD plans to commence a Phase II clinical trial for this new drug in the Mainland next year to verify its effectiveness and safety as a treatment for remission maintenance for ulcerative colitis. Developed based on traditional Chinese medicine formulation Ulcerative colitis, a form of inflammatory bowel disease, is becoming increasingly prevalent. It has a rising morbidity particularly in China and other Asian countries. Its main symptoms include diarrhea, rectal bleeding and abdominal cramps, resulting in a reduced quality of life for patients. Ulcerative colitis can be broadly divided into active and remission stages. Currently the main treatment objectives of the disease are to relieve symptoms, sustain the remission period, and reduce recurrence. Existing treatment options for ulcerative colitis cannot completely maintain remission, nor prevent its recurrence. In search of more effective ways to relieve ulcerative colitis, the research team developed a Chinese herbal formulation CDD-2103, with nine Chinese herbal medicines including Codonopsis Radix (dang shen) and Curcumae Longae Rhizoma (jiang huang), based on years of clinical experience. CDD-2103 is formulated for to maintain remission in ulcerative colitis patients who exhibit symptoms of spleen deficiency and internal accumulation of damp heat. According to a clinical study conducted in Hong Kong by the research team, patients who used CDD-2103 in a decoction format demonstrated good tolerability with no adverse effects reported. The research team has developed the CDD-2103 granule in accordance with NMPA's stringent quality control standards, and completed a series of basic experimental studies including preclinical pharmaceutical, pharmacology and non-clinical safety evaluations. Results of the preclinical studies showed that CDD-2103 suppressed the progression of colitis by improving the tolerogenic immune microenvironment, which is achieved by mediating the differentiation of regulatory T cells and reducing the number of inflammatory macrophages in the colon, as well as strengthening the tight junction proteins in the mucosal barriers. The research findings have been published in a number of scientific journals including Journal of Advanced Research, Phytomedicine and Journal of Ethnopharmacology. Professor Bian Zhaoxiang, Associate Vice-President (Clinical Chinese Medicine) and Director of CDD at HKBU, said: "We are delighted that CDD-2103 has obtained approval to carry out a Phase II clinical trial in the Mainland. The Centre is optimistic that it can improve patients' quality of life. CDD-2103 is a novel Chinese herbal formulation developed based on the modified ancient formulations combined with modern technology. Obtaining clinical trial approval from NMPA for this new drug is one of the important milestones of the Centre, which is also a recognition of the efforts of the research team in the development of novel Chinese herbal drugs." Phase II trial focuses on safety and effectiveness CDD will launch a randomised, double-blind, and placebo-controlled clinical trial in the Mainland in 2025 to evaluate the drug's safety and effectiveness in ulcerative colitis patients in remission. Dr Tan Hor Yue, Assistant Professor of CDD stated: "It is anticipated that the larger scales of clinical trials will be completed in the next five years in order to confirm CDD-2103's therapeutic effect and safety in treating ulcerative colitis. After collecting sufficient data regarding the drug's safety and efficacy, the Centre will submit an application for NMPA's new drug approval, with the objective of obtaining authorisation for the sales of CDD-2103 in the market". CDD, located in the Hong Kong Science Park, is funded by the Innovation and Technology Commission's InnoHK initiative. It is the only centre focusing on the research and development of Chinese herbal medicines at a local university. Since its establishment in 2020, CDD has been focusing on innovative Chinese medicine research for gastrointestinal and immune-related diseases such as chronic constipation and ulcerative colitis. SOURCE Hong Kong Baptist University

HONG KONG, Aug. 27, 2024 /PRNewswire/ -- A research team led by Hong Kong Baptist University (HKBU) has discovered that phosphocholine, an important component in the body's metabolism, could counteract the adverse effects of PM2.5 toxicity on lung cells. This discovery highlights the therapeutic potential of phosphocholine in treating lung diseases associated with PM2.5 such as asthma, chronic obstructive pulmonary disease and lung cancer, and contributes to developing health measures against air pollution. Continue Reading Professor Cai Zongwei, Chair Professor of the Department of Chemistry and Director of the State Key Laboratory of Environmental and Biological Analysis (left), and Dr Yang Zhu, Assistant Professor of the Department of Biology at HKBU (right), discover the potential of phosphocholine in counteracting PM2.5 toxicity in the lungs. The research findings have been published in the international academic journal Proceedings of the National Academy of Sciences. PM2.5 increases health risks The World Health Organisation has linked air pollution to an estimated seven million deaths annually, and recognising it as the leading environmental risk factor globally. PM2.5, a major air pollutant, increases the risk of health problems such as heart and lung diseases. Every type of PM2.5 component possesses distinct impacts on human health. However, the understanding of the toxicity effects of individual PM2.5 components remains limited, and the respective preventive solutions for PM2.5-associated health problems are lacking. To understand the effects of different PM2.5 components on the underlying cell metabolism associated with lung diseases, a team led by Professor Cai Zongwei, Chair Professor of the Department of Chemistry and Director of the State Key Laboratory of Environmental and Biological Analysis, and Dr Yang Zhu, Assistant Professor of the Department of Biology at HKBU, analysed a total of 82 components in PM2.5 samples collected from Taiyuan in Shanxi Province and Guangzhou in Guangdong Province between 2017 and 2018. It was found that the overall PM2.5 profiles were similar in both cities. Inorganic ions are the most abundant pollutants, followed by metals and organic compounds polycyclic aromatic hydrocarbons (PAHs). However, a large difference was observed in the relative proportions of PAHs and their derivatives. PM2.5 composition contributes to toxicity The research team discovered that the proportion of PAHs was significantly higher in Taiyuan, especially during the heating season. Since the abundance of PAHs is closely associated with coal combustion, the result suggested that coal combustion was one of the major sources of PM2.5 in the city. Conversely, the seasonal variance of PAHs in Guangzhou was significantly lower. Traffic emissions were the predominant PM2.5 in Guangzhou. Given the disparity in pollutant composition, the research team conducted toxicity and health risk analysis of PM2.5 samples from both cities. A cytotoxicity test revealed that the PM2.5 from winter Taiyuan exhibited much stronger toxicity than the samples from Guangzhou or from other seasons of Taiyuan with the same PM2.5 concentration, as indicated by cell viability which measures the proportion of healthy living cells. Assessment using the incremental lifetime cancer risk model, which estimates increased cancer risk from carcinogen exposure, highlighted that the regional difference in cancer risks linked to PAHs and its derivatives nitro-PAHs' concentration was much higher than the variation in overall PM2.5 concentration. These findings underscore that PM2.5 toxicity cannot be solely attributed to its concentration but also to its composition. Phosphocholine counteracts PM2.5 toxicity The research team further employed correlation analysis to examine the impact of specific PM2.5 components on metabolic alterations in lung cells, and identified 11 metabolites that showed a significant correlation with PM2.5 components. Among these metabolites, the researchers focused on the functions of eight ones whose amount reduced significantly after PM2.5 exposure. Subsequent experiments demonstrated that only supplementing phosphocholine to PM2.5-exposed cells was effective in both rescuing cell viability and stimulat ing adenosine triphosphate (ATP) production. ATP is a critical molecule for energy storage, which provides the energy needed for a wide range of cellular processes within living cells. Under normal circumstances, lung cells primarily rely on glucose for energy production. However, PM2.5 conditions might impair energy supply from glucose. Fatty acid oxidation is a process in cells that breaks down fatty acids to generate energy. Under normal conditions, the utilisation of fatty acid oxidation pathway contributes minimally to energy production in lung cells. It was found that phosphocholine can reprogramme cellular metabolism to increase fatty acid oxidation to meet the shortfall in energy supply during the PM2.5 challenge, which helps to alleviate cellular dysfunction induced by PM2.5. Professor Cai said: "Our findings highlighted the potential of phosphocholine as a therapeutic agent for lung diseases associated with PM2.5. As air pollution caused by PM2.5 has been recognised as a significant global health risk factor, our discovery provides the prospect of developing novel treatments for related health issues, potentially helping to address this public health challenge." In future, the research may also contribute to the development of diagnosis protocol for lung diseases caused by PM2.5 apart from its potential as a therapeutic agent. SOURCE Hong Kong Baptist University

医疗药物发展史上，单克隆抗体药物（以下简称为“单抗”）是几十年来最重要的治疗手段之一。自1986年FDA批准第一批单抗以来，抗体类药物占FDA新药批准的近五分之一。与此同时，具有广谱抗肿瘤特性的小分子药物也占据了获批药物的半壁江山。 但相比于这两者，香港浸会大学张戈教授似乎更加青睐核酸适配体药物。“适配体本身的序列多样性为其带来了与小分子药物和单抗不同的独特性质。在临床应用中，相较于单抗，核酸适配体因其分子量小，表现出更好的组织渗透性和更低的免疫原性，其筛选周期也远短于单抗。与小分子药物相比，适配体的选择性和特异性则更高。”张戈教授如是说道。 看准适配体药物的诸多优势，张戈教授联合其学生何伊欣博士共同成立了安沛治疗，致力于开发适配体创新药物。安沛治疗团队告诉动脉网，团队将核酸适配体与药物结合，甚至将其与siRNA技术结合，来赋予核酸适配体药物拓展更广泛适应症的可能性。 布局三大技术平台， 提高适配体药物成药性 在药物研发的领域，时间是创新的双重考验，而想要加快适配体药物研发速度，安沛治疗首先要解决三个关键问题：一是如何高效筛选获得高亲和性的适配体，二是如何延长适配体的消除半衰期，三是如何提高适配体与蛋白分子靶点的亲和力。为此，安沛治疗构建了三大技术平台，覆盖从适配体发现到长效性设计再到高亲和性优化。 首先，依托AI赋能的高通量筛选平台，安沛治疗利用先进算法深度挖掘海量SELEX数据，精准识别并生成潜在的高亲和性适配体序列，极大地缩减了后续实验验证的范围，有效降低了研发成本与时间消耗。 在适配体药物长效性设计上，安沛治疗则创新性地采用双分子修饰策略，通过筛选与血清白蛋白紧密结合的小分子化合物，成功延长了适配体在体内的半衰期。安沛治疗实验数据表明，这一策略将硬骨抑素适配体在大鼠体内的半衰期提升至12天，是传统PEG修饰及单抗的4倍，显著增强了药物的持久疗效与患者的治疗依从性。 “适配体若要成药，必须具备高亲和性。”张戈特别强调道。为此，安沛治疗还开发了先进的亲和修饰平台技术。团队前期筛选出与靶蛋白具有高亲和力的修饰dU-C5的疏水分子，将它们应用到pre-SELEX阶段后，筛选获得具有高亲和力的适配体；为进一步模拟抗体-抗原之间的高亲和力、高特异性相互作用，团队又在post-SELEX阶段直接赋予适配体氨基酸侧链，并保留了适配体碱基的完整化学结构；从pre-SELEX阶段到post-SELEX阶段，团队经过三代亲和性修饰技术的迭代，在提高硬骨抑素适配体对骨硬化素蛋白的亲和力上越来越显著，其亲和性几乎是同靶点单抗的10倍。 “自研+合作”， 核心产品已获FDA孤儿药认定 在成功创新三大技术平台后，安沛治疗正式启动了三项自主研发管线和两项合作研发项目，致力于将核酸适配体创新药物应用到多种适应症上。 作为安沛治疗自研管线的明星产品，APC001是一种硬骨抑素适配体抑制剂，为骨质疏松、低磷佝偻病及成骨不全患者带来新希望。值得一提的是，其治疗成骨不全症及低磷佝偻病的新分子已获得美国FDA孤儿药(ODD)及儿童罕见病药（RPDD）认定，预计该产品将在2025年第三季度在中美两地同时提交IND申请。 第二个管线针对抗纤维化相关疾病，团队选择了杜氏肌营养不良（DMD）作为首个适应症。目前，安沛治疗也已经选定了特定的靶点适配体分子，并在动物实验中初步验证了其药效。此外，为了更全面地评估药物效果，张戈正在带领团队进行肺纤维化的药效研究，以期确定最佳的适应症开发方向。 而在更具探索性的第三项自研管线中，安沛治疗开发出一种针对三阴乳腺癌等难治性疾病的创新药物。该药物采用适配体PROTAC模式，靶向细胞内硬骨抑素降解。目前，候选分子已完成分子优化并在动物模型中初步验证其疗效，下一步将聚焦于药物分布及入胞效能等关键参数的评估，为后续IND申请做准备。 为了拓宽研发边界，安沛治疗的合作管线更是强强联合。在适配体偶联药物以及适配体siRNA药物肝外递送系统研发上探索，安沛治疗正与一家专注于siRNA药物的初创公司合作，开发针对多发性骨髓瘤的新靶点siRNA药物递送系统。据了解，团队成功筛选出靶向肿瘤细胞的适配体，并与siRNA高效耦联，实现了在细胞膜上的有效结合与内吞，同时在小鼠模型中展现出良好的药效。 科技赋能商业， 团队正在筹备融资 作为一家高校孵化的企业，安沛治疗团队分工是明确且互补。 何伊欣向动脉网介绍：“大学团队专注于分子机制与靶点通路的深入研究，为药物研发奠定坚实的理论基础。”另一方面，公司团队侧重于产业化转化工作。一旦靶点得到确认，公司团队就迅速接手，进行适配体的筛选、候选分子的优化以及各种成药性评价。 在谈及下一个适应症或管线的选择时，何伊欣强调了公司策略的审慎和精准。他指出，在当前资本寒冬的背景下，安沛治疗不会盲目扩张追求广泛的管线布局，而是根据自身资源的丰富程度进行深思熟虑的决策。目前，安沛治疗更倾向于选择在分子机制上具有独特性、且当前药物模式难以有效解决的靶点。 而在资金规划方面，何伊欣则透露，团队正在积极筹备融资，这笔资金将主要用于IND申报的内部流程和工作，部分资金还将用于团队功能的进一步完善，如增强临床监管方面的内部能力。 作为安沛治疗的重要合作伙伴，尚骏投资合伙人陈奕群也向动脉网表示，安沛治疗正处于加速发展的关键阶段，首要任务是充分利用此次融资机遇，为企业的跨越式发展提供强劲动力。除了资金支持外，尚骏投资还计划在品牌塑造与宣传策略上给予安沛治疗全方位的支持，提升市场知名度和影响力。 如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台