HWS-113

近日，人福医药自主研发的IL-31RA人源化单克隆抗体注射用HWS113 Ⅰ期临床试验顺利完成首例受试者入组，标志着该产品正式进入人体试验阶段。 这项“在健康研究参与者中评价注射用HWS113单次给药的安全性、耐受性、免疫原性及药代动力学特征的I期、随机、双盲、单中心、剂量递增、安慰剂对照临床研究”，由山东第一医科大学第一附属医院赵维主任牵头，目的是在健康研究参与者中评价注射用HWS113单次皮下给药的安全性、耐受性、药代动力学特征和免疫原性。 关于IL-31RA单抗 白细胞介素-31（IL-31）归属于IL-6细胞因子家族，亦被称作“致痒细胞因子”。该因子主要由活化Th2细胞与角质形成细胞分泌，是结节性痒疹、特应性皮炎等Th2型炎症皮肤病发病过程中调控瘙痒的核心介质。IL-31可与感觉神经元表面异源二聚体受体IL-31RA/OSMRβ相结合，启动下游JAK/STAT、PI3K/AKT及MAPK信号通路，向中枢传导痒觉信号，诱发剧烈瘙痒[1]。与此同时，IL-31可促进感觉神经纤维增生与轴突延伸，降低皮肤痒觉阈值，造成外周神经敏化，使瘙痒迁延为慢性病程。 IL-31除主导痒觉传导外，还深度参与Th2型炎症进程。该因子可刺激角质形成细胞、巨噬细胞释放各类促炎细胞因子与趋化因子，募集并活化免疫细胞，放大局部炎症反应；还可抑制角质形成细胞正常分化，破坏皮肤屏障稳态，进一步促使表皮细胞大量释放炎症介质与致痒物质，形成瘙痒-炎症恶性循环。此外，IL-31可作用于真皮成纤维细胞，诱导胶原合成与炎症因子分泌，启动皮肤组织纤维化重塑进程[2]。 临床标本检测显示，IL-31在特应性皮炎、结节性痒疹等多种瘙痒性皮肤病皮损中表达显著升高，其中结节性痒疹病灶内IL-31 mRNA表达水平可上调至正常组织的50倍以上[3]。特异性阻断 IL-31RA，既可直接切断痒觉信号传导，又能下调下游Th2、Th17介导的炎症应答，抑制神经生长因子（NGF）引发的神经元功能异常，并逆转角质形成细胞过度增殖与促纤维化通路异常激活[4]。 慢性瘙痒是指瘙痒症状持续时间大于6周，涵盖各类病因引发的顽固性瘙痒病症。该病人群患病率较高，可显著损害患者躯体健康与心理健康，现阶段仍缺少疗效确切的干预方案。以IL-31RA为作用靶点的单克隆抗体具备高度靶向特异性，可精准阻断痒觉信号通路的传导，在提升临床疗效、降低全身性不良反应方面具备突出优势。截至目前，国内暂未有针对IL-31RA靶点的治疗药物获批上市。 关于HWS113 HWS113是由人福医药自主研发、靶向IL-31RA的全新人源化单克隆抗体。本品对IL-31RA具备高结合亲和力，可强效阻断IL-31信号通路。 动物药效试验结果显示，该药物可明显改善瘙痒与炎症症状，药效优于境外已上市同靶点同类产品。本品不干扰IL-31家族其他细胞因子（IL-6、抑瘤素M）介导的信号通路，同时常规毒性试验、局部刺激性试验与免疫毒性试验结果均提示药物毒性水平低，整体安全性良好。 注射用HWS113系国内首个进入临床试验阶段的IL-31RA靶向单克隆抗体药物。随着研发进程稳步推进，该药物有望早日落地临床，为慢性瘙痒患者开辟精准治疗新路径，弥补当前临床有效治疗药物不足的现状。 关于人福医药研究院 人福医药研究院是人福医药集团的中央研发机构，是集团创新发展的核心引擎，承载着集团战略转型使命，为构建全球研发体系、冲刺世界一流生命科技企业提供核心支撑。研究院聚焦创新药研发，以满足未被满足的临床需求为导向，在集团的优势治疗领域持续深耕，凭借强劲的自主研发与转化能力确立和巩固集团在核心细分赛道的研发优势。研究院将以患者需求为初心、科技创新为引擎，深耕生命健康领域，用优质创新药物赋能人类健康事业，助力集团打造全球竞争力。如需了解更多研发动态，欢迎关注“人福医药研究院”微信公众号。 First Subject Enrolled in Phase Ⅰ Trial of Humanwell Healthcare’s HWS113 for Pruritus Humanwell Healthcare has successfully dosed the first subject in the Phase Ⅰ clinical trial of HWS113, an investigational humanized monoclonal antibody against IL-31RA. The Phase Ⅰ, randomized, double-blind, single-center, dose-escalation, placebo-controlled study of HWS113 has been initiated under the leadership of Principal Investigator Dr. Wei Zhao at the First Hospital Affiliated with Shandong First Medical University. The trial is designed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of a single subcutaneous dose of HWS113 in healthy volunteers. About Anti-IL-31 Receptor Antibody Interleukin-31 (IL-31), a member of the IL-6 cytokine family, has been characterized as a pruritogenic cytokine. It is primarily secreted by activated Th2 cells and keratinocytes and acts as a key itch mediator in Th2-type inflammatory skin diseases such as prurigo nodularis and atopic dermatitis. IL-31 binds to the heterodimeric receptor IL-31RA/OSMRβ on sensory neurons, activating downstream JAK/STAT, PI3K/AKT, and MAPK signaling pathways. This relays itch signals to the central nervous system and elicits intense pruritus[1]. Moreover, IL-31 promotes sensory nerve fiber sprouting and axonal elongation, lowers the cutaneous itch threshold, and induces peripheral sensitization, thereby driving the chronification of pruritus. Beyond its central role in itch signaling, IL-31 is critically involved in Th2-type inflammatory processes. It stimulates keratinocytes and macrophages to release various pro-inflammatory cytokines and chemokines, which recruit and activate immune cells, amplifying local inflammatory responses. IL-31 also inhibits normal keratinocyte differentiation and disrupts skin barrier homeostasis, further promoting the excessive release of inflammatory mediators and pruritogens from epidermal cells, thereby perpetuating an itch-inflammation vicious cycle. Furthermore, IL-31 acts on dermal fibroblasts to induce collagen synthesis and the secretion of pro-inflammatory cytokines, initiating cutaneous fibrosis and tissue remodeling[2]. Analysis of clinical specimens has shown that IL-31 expression is significantly elevated in skin lesions of various pruritic dermatoses, including atopic dermatitis and prurigo nodularis. Notably, IL-31 mRNA levels in prurigo nodularis lesions can be upregulated by more than 50-fold relative to normal tissue[3]. Specific blockade of IL-31RA not only directly interrupts itch signaling, but also downregulates Th2- and Th17-mediated inflammatory responses, inhibits neuronal dysfunction induced by nerve growth factor (NGF), and suppresses keratinocyte hyperproliferation and aberrant activation of pro-fibrotic pathways[4]. Chronic pruritus is defined as itch lasting more than six weeks, encompassing a range of refractory pruritic disorders arising from various etiologies. The condition is highly prevalent in the general population and can significantly impair patients' physical and mental health. At present, effective treatment options remain limited. Anti-IL-31 Receptor Antibody are highly target-specific, allowing precise blockade of itch signaling pathway, and offer distinct advantages in both clinical efficacy and the reduction of systemic adverse effects. To date, no anti-IL-31 receptor antibody has been approved for marketing in China. About HWS113 HWS113 is a novel, humanized anti-IL-31 receptor monoclonal antibody, independently developed by Humanwell Healthcare. The antibody exhibits high binding affinity for IL-31RA and potently blocks the IL-31 signaling pathway.  In vivo pharmacodynamic studies have shown that HWS113 significantly relieves pruritus and inflammation, demonstrating superior efficacy compared to anti-IL-31RA therapies currently marketed outside China. Importantly, HWS113 does not interfere with the signaling pathways mediated by other members of the IL-6 cytokine family, such as IL-6 and Oncostatin M. Furthermore, results from general toxicology, local irritation, and immunotoxicity studies have collectively demonstrated a favorable overall safety and low-toxicity profile. HWS113 is the first anti-IL-31RA monoclonal antibody to enter clinical trials in China. As its clinical development steadily advances, HWS113 is poised to offer a novel precision treatment option for patients suffering from chronic pruritus, addressing a significant unmet medical need. About Humanwell R&D Institute Humanwell Pharmaceutical Research and Development Institute is the central R&D organization of Humanwell Healthcare and the core engine driving Humanwell's innovation-led development. It undertakes Humanwell's strategic transformation mission and provides essential support for building a global R&D system and advancing toward a world-class life sciences enterprise. Focused on innovative drug development and guided by unmet clinical needs, the Institute continues to deepen its expertise in Humanwell's key therapeutic areas, leveraging strong in-house R&D and translational capabilities to establish and reinforce Humanwell's research advantages in core niche segments. With patient needs as its founding mission and technological innovation as its driving force, the Institute is committed to advancing the field of life and health sciences, empowering human health through high-quality innovative medicines, and helping Humanwell build global competitiveness. For more updates on our R&D progress, follow the official WeChat account "Humanwell Pharmaceutical Research Institute". 参考文献： [1]Datsi A, Steinhoff M, Ahmad F, et al. Interleukin-31: The "itchy" cytokine in inflammation and therapy. Allergy. 2021 Oct;76(10):2982-2997. [2]Nemmer JM, Kuchner M, Datsi A, et al. Interleukin-31 Signaling Bridges the Gap Between Immune Cells, the Nervous System and Epithelial Tissues. Front Med (Lausanne). 2021 Feb 10;8:639097. [3]Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006 Feb;117(2):411-7. [4]Tsoi LC, Hacini-Rachinel F, Fogel P, et al.. Transcriptomic characterization of prurigo nodularis and the therapeutic response to nemolizumab. J Allergy Clin Immunol. 2022 Apr;149(4):1329-1339. 声明： 1. 本资讯旨在分享医药领域的科研进展与前沿信息，仅供医疗卫生专业人士进行学术交流与参考，不构成任何广告或产品推荐。 2. 本资讯中涉及的信息不能替代专业医疗指导，所有医疗决策请遵从医疗卫生专业人士的意见或指导。 3. 本资讯任何前瞻性陈述均基于当前预测，实际结果可能存在不确定性。 4. 对于依赖本文信息作出的任何决定或行动，本公司不承担相关责任。

来源：湖北日报、光谷融媒体中心在武汉禾元生物科技股份有限公司，详细了解企业发展历程，他听取全球首个“稻米造血”一类创新药研发应用情况介绍，希望企业充分发挥原创性、颠覆性创新引领优势，积极扩大产品生产应用，进一步加强新药研发，让创新成果更好服务群众健康。在武汉凯德维斯生物技术有限公司，认真察看企业核心产品研发情况，勉励企业锚定基因诊疗前沿领域，坚定不移加大科技创新力度，为攻克肿瘤疾病作出更大贡献。他指出，生物医药产业是关系国计民生和国家安全的战略性新兴产业。要充分发挥企业创新主体作用，推动企业主导的产学研用深度融合，加强原始创新和关键核心技术攻关，研发生产更多优质高效的好药新药，不断增进人民健康福祉。要根据医药企业成长规律特点，系统搭建覆盖技术研发、中试转化、企业孵化、产业应用的科技金融服务体系，加大政策支持力度，推动我省生物医药产业提质升级。7月14日，省委书记关志鸥在武汉市调研医工交叉融合和生物医药产业发展，武汉市委书记盛阅春参加调研。近期，光谷多家生物医药企业迎来新进展：6家医药研发服务企业签约扩产；朗来科技首个创新药拟纳入突破性疗法；人福医药治疗用生物制品1类新药HWS113获批临床……一起来看：光谷6家医药研发服务企业签约扩产国家药监局发布的信息显示，今年一季度，中国创新药对外授权交易总额突破600亿美元，接近2025年全年的一半。创新药出海“正酣”，做研发生产服务的企业也跟着忙了起来。日前，在湖北省细胞与基因治疗（CGT）产业专场对接会上，瑞杰迈、尚纯生物、天勤生物、永安康健、宏韧医药、劲帆生物等6家光谷生命健康企业签约，签约总额超5亿元，集体按下扩产“加速键”。这些企业中，不少是CRO（医药研发生产服务）企业，此次签约将扩建实验室、建设AI平台、补齐基因治疗新业务等。CRO是药企的“研发搭档”。从药物发现、动物实验到临床试验，药企常把部分环节交给这类专业机构完成，以降低成本、提高研发效率。宏韧医药主要为制药企业提供临床生物分析和非临床药代动力学服务，企业董事会秘书宁红心说：“目前企业临床生物分析能力已处于国内头部，非临床药代动力学产能有限，需要扩充一些产能去满足市场需求，计划把非临床动物实验室从5000平方米扩到7000平方米。”劲帆医药技术人员正分析实验数据劲帆医药专为基因药研发企业生产递送载体，公司CEO何晓斌介绍，基因药进人体细胞，就像卫星靠运载火箭，“我们就是造‘火箭’的平台”。企业已投1.5亿元建生产平台，前不久刚获得光谷本地国有平台领投，这次签约就是要用融资资金，再搭“先进疗法一站式加速平台”，把业务从基因治疗扩展到体内CAR-T疗法等新赛道。天勤生物是一家为药企提供非临床评价服务的CRO公司，此次签约项目为AI医药研发创新中心，用人工智能帮药企更快筛出新药、验证其成药性。公司董事长助理朱湘涛介绍，该项目规划建设8万平方米，目前已投用2万平方米，累计投资达3.5亿元。受益于市场回暖，公司订单已排到明年，今年营收预计超5亿元，同比增长30%到40%。天勤生物AI医药研发创新中心今年以来，光谷已有艾米森、滨会生物、纽福斯等多家生命健康企业进入上市辅导备案，拟登陆资本市场融资，加速研发与产能扩张。在医药外包服务领域，光谷已聚集鼎康生物、赛维尔生物等20余家重点产业链企业，形成从临床前研究到商业化生产的全链条服务能力。