更新于：2024-04-01

IL-23R

白细胞介素23受体

更新于：2024-04-01

基本信息

别名

IL-23 receptor、IL-23R、IL23R

+ [2]

简介

Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-Stat signaling cascade. IL23 functions in innate and adaptive immunity and may participate in acute response to infection in peripheral tissues. IL23 may be responsible for autoimmune inflammatory diseases and be important for tumorigenesis.

关联

项与 IL-23R 相关的药物

PN-235

靶点

IL-23R

作用机制

IL-23R抑制剂

在研机构

Janssen Pharmaceutica NV [+3]

原研机构

Protagonist Therapeutics, Inc.

在研适应症

红皮病性银屑病 [+3]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

PN-232

靶点

IL-23R

作用机制

IL-23R抑制剂

在研机构

Protagonist Therapeutics, Inc.

原研机构

Protagonist Therapeutics, Inc.

在研适应症-

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

APG-2305

靶点

IL-23R x TNFR2 x VEGFR2

作用机制

IL-23R抑制剂 [+2]

在研机构-

原研机构

Allostera Pharma, Inc.

在研适应症-

非在研适应症

银屑病关节炎

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 IL-23R 相关的临床试验

NCT06220604 / Recruiting临床3期

A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled and Deucravacitinib Active Comparator-controlled Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis

The purpose of the study is to evaluate how effective JNJ-77242113 is in participants with moderate to severe plaque psoriasis compared to placebo and deucravacitinib.

开始日期2024-03-09

申办/合作机构

Janssen Research & Development LLC

CTRI/2024/01/061432 / Recruiting临床2期

A Phase 2b Multicenter, Randomized, Placebo- Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Moderately to Severely Active Ulcerative Colitis - ANTHEM-UC

开始日期2024-02-20

申办/合作机构-

NCT06295692 / Recruiting临床3期

A Phase 3, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Participants With Generalized Pustular Psoriasis or Erythrodermic Psoriasis

The purpose of this study is to evaluate how effective JNJ-77242113 is in participants with generalized pustular psoriasis (GPP) or erythrodermic psoriasis (EP).

开始日期2024-02-09

申办/合作机构

Janssen Pharmaceuticals, Inc.

100 项与 IL-23R 相关的临床结果

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100 项与 IL-23R 相关的转化医学

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0 项与 IL-23R 相关的专利（医药）

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1,411

项与 IL-23R 相关的文献（医药）

2024-02-23·Medicine

Interleukin gene polymorphisms and alopecia areata: A systematic review and meta-analysis.

Review

作者: Zasia Hossain Tishe ; Sanjana Shawkat ; Meherun Nessa Popy ; Ashfaq Ahmed ; Sadia Biswas Mumu ; Mohd Nazmul Hasan Apu ; Md Shaki Mostaid

BACKGROUND:

Alopecia areata (AA) is an autoimmune disease which results in non-scarring hair loss on the scalp or any surface with hair. Several genetic polymorphisms of the interleukin genes have been linked with this disease but the results are inconsistent. This systematic review and meta-analysis were done to find the association between rs3118470, rs2275913, rs3212227, and rs10889677 of the IL2RA, IL17A, IL12B, and IL23R genes, respectively, of the interleukin family with alopecia areata.

METHODS:

A comprehensive search for relevant research articles was conducted in Pubmed, Google Scholar, and Embase databases. Our search yielded 8 relevant articles with 1940 cases and 1788 controls. The odds ratio with 95% confidence intervals was calculated using fixed effect and random effect models. Heterogeneity was determined using the Q-test and I2 test. Publication bias was determined and funnel plots were used to adjust the odds ratio.

RESULTS:

We found a significant risk effect for rs3118470 of the IL2RA gene with alopecia areata in the dominant model (CC + CT vs TT; OR = 1.54, 95% confidence interval = 1.05-2.26, P < .05, I2 = 69.03%) and homozygous model (CC vs TT; OR = 2.00, 95% confidence interval = 1.07-3.71, P < .05, I2 = 72.84%). For the other single nucleotide polymorphisms, we could not find any statistically significant association with the disease.

CONCLUSION:

Our analysis showed that mutation of rs3118470 of IL2RA gene possesses a significant risk effect for alopecia areata. Future studies with larger sample sizes and ethnic backgrounds are warranted to confirm our findings.

2024-02-20·mBio

Investigating the impact of antibiotic-induced dysbiosis on protection from Clostridium difficile colitis by mouse colonic innate lymphoid cells.

Article

作者: Md Jashim Uddin ; Brandon Thompson ; Jhansi L Leslie ; Casey Fishman ; Katia Sol-Church ; Pankaj Kumar ; William A Petri

Innate lymphoid cells (ILCs) play a critical role in maintaining intestinal health in homeostatic and diseased conditions. During Clostridium difficile infection (CDI), IL-33 activates ILC2 to protect from colonic damage and mortality. The function of IL-33 and ILC is tightly regulated by the intestinal microbiota. We set out to determine the impact of antibiotic-induced disruption of the microbiome on ILC function. Our goal was to understand antibiotic-induced changes in ILC function on susceptibility to C. difficile colitis in a mouse model. We utilized high-throughput single-cell RNAseq to investigate the phenotypic features of colonic ILC at baseline, after antibiotic administration with or without IL-33 treatment. We identified a heterogeneous landscape of colonic ILCs with gene signatures of inflammatory, anti-inflammatory, migratory, progenitor, plastic, and antigen-presenting ILCs. Antibiotic treatment decreased ILC2 while coordinately increasing ILC1 and ILC3 phenotypes. Notably, Ifng⁺, Ccl5⁺, and Il23r⁺ ILC increased after antibiotics. IL-33 treatment counteracted the antibiotic effect by downregulating ILC1 and ILC3 and activating ILC2. In addition, IL-33 treatment markedly induced the expression of type 2 genes, including Areg and Il5. Finally, we identified amphiregulin, produced by ILC2, as protective during C. difficile infection. Together, our data expand our understanding of how antibiotics induce susceptibility to C. difficile colitis through their impact on ILC subsets and function.IMPORTANCEClostridium difficile infection (CDI) accounts for around 500,000 symptomatic cases and over 20,000 deaths annually in the United States alone. A major risk factor of CDI is antibiotic-induced dysbiosis of the gut. Microbiota-regulated IL-33 and innate lymphoid cells (ILCs) are important in determining the outcomes of C. difficile infection. Understanding how antibiotic and IL-33 treatment alter the phenotype of colon ILCs is important to identify potential therapeutics. Here, we performed single-cell RNAseq of mouse colon ILCs collected at baseline, after antibiotic treatment, and after IL-33 treatment. We identified heterogeneous subpopulations of all three ILC subtypes in the mouse colon. Our analysis revealed several potential pathways of antibiotic-mediated increased susceptibility to intestinal infection. Our discovery that Areg is abundantly expressed by ILCs, and the protection of mice from CDI by amphiregulin treatment, suggests that the amphiregulin-epidermal growth factor receptor pathway is a potential therapeutic target for treating intestinal colitis.

2024-02-20·Journal of leukocyte biology

Differential requirement for IL-2 and IL-23 in the differentiation and effector functions of Th17/ILC3-like cells in a human T cell line.

Article

作者: Momtazkari Sarah ; Dev Choudhury Anahita ; Wei Ern Yong Zachary ; Dong Le Thanh ; Nguyen Canh Hiep ; Harada Kenichi ; Toshiyuki Hori ; Osato Motomi ; Takahashi Chiaki ; Cai Ping Koh ; Chih-Cheng Voon Dominic

A well-documented Achilles heel of current cancer immunotherapy approaches is T cell exhaustion within solid tumor tissues. The pro-inflammatory cytokine interleukin-23 (IL-23) has been utilised to augment chimeric antigen receptor (CAR)-T cells survival and tumor immunity. However, in-depth interrogation of molecular events downstream of IL-23/IL23R signaling is hampered by a paucity of suitable cell models. The current study investigates the differential contribution of IL-2 and IL-23 to the maintenance and differentiation of the IL-23 responsive Kit225 T-cell line. We observed that IL-23 enhanced cellular fitness and survival but was insufficient to drive proliferation. IL-23 rapidly induced phosphorylation of STAT1, 3 and 4, and mRNA expression of IL17A, the archetypal effector cytokine of Th17 cells, but not their lineage markers RORC and NCR1. These observations suggest that IL-23 endowed Th17/ILC3-like effector function but did not promote their differentiation. In contrast, spontaneous differentiation of Kit225 cells towards a Th17/ILC3-like phenotype was induced by prolonged IL-2 withdrawal. This was marked by strongly elevated basal IL17A and IL17F expression and the secretion of IL-17. Together, our data present Kit225 cells as a valuable model for studying the interplay between cytokines and their contribution to T cell survival, proliferation, and differentiation.

116

项与 IL-23R 相关的新闻（医药）

2024-03-29

·动脉网

下一个吸金靶点浮现水面，同类最佳来自中国？

下一个吸金靶点已经浮现水面。3月初，以TYK2管线为核心的Biotech公司Alumis宣布了2.59亿美元的C轮融资，据Fierce Biotech的统计，这是2024年迄今为止初创Biotech公司获得的最大融资金额。在此之前，Alumis分别在2021年5月、2022年1月迅速完成了7000万美元A轮融资、2亿美元B轮融资，迄今已经累计融资超5.2亿美元。Alumis的核心产品为ESK-001，一种高选择性且有Best-in-Class潜力的TYK2抑制剂，即将开始用于治疗中重度斑块状银屑病的3期试验，并支持正在进行的两项治疗系统性红斑狼疮和非传染性葡萄膜炎的2期临床试验；以及第二代TYK2抑制剂A-005，一项First-in-Class针对多发性硬化等神经炎症性疾病的临床前项目。同时，由于ESK-001最先来自于海思科下属子公司FT集团的授权，今年下半年ESK-001的3期临床启动后，海思科预计将收到约1280万美元的里程碑付款。Alumis也并不是今年唯一获得大额融资的TYK2公司。Sudo Biosciences宣布于2024年1月完成了第二次B轮融资，并在2月额外筹集了3000万美元，使这家TYK2开发公司的B轮融资额达到了1.47亿美元。另一家TYK2公司Myrobalan Therapeutics也在1月得到了2400万美元的A轮融资。TYK2是JAK激酶家族的一个分支，但由于发现时间较早，没有按照JAK激酶的命名方式，所以TYK2抑制剂也属于广义上的JAK抑制剂之一。目前已上市的TYK2抑制剂仅有一款，为FDA在2022年9月批准的BMS的Sotyktu（Deucravacitinib，氘可来昔替尼），用于治疗中至重度银屑病。Sotyktu是市场上唯一一款用于治疗慢性炎性疾病且没有黑框的JAK，这归功于TYK2靶点作用的专一以及药物对TYK2本身的高选择性（通过变构抑制实现），几乎不会产生脱靶毒性。Sotyktu在2023年获得了1.7亿美元收入，BMS预计到2030年销售额将超过40亿美元。而TYK2领域中最著名的一笔交易，是2022年底武田与Nimbus Therapeutics围绕TAK-279（此前名为NDI-034858）的总金额60亿美元的合作，其中首付款为40亿美元。TAK-279的开发参考了BMS的Deucravacitinib，具有更高的体外选择性。具有戏剧意义的是，在去年底的美国风湿病学会（ACR）上，武田的一张海报被人窃走，海报上展示的正是TAK-279的2b期临床数据，这也侧面印证了TAK-279以及TYK2的火热程度。自免江湖轮动之时，TYK2的蓝海已经展现。TYK2欲戴王冠JAK-Stat通路在炎症、代谢、肿瘤中发挥重要作用，全球目前已经获批11款JAK抑制剂，除去用于骨髓纤维化治疗的JAK2抑制剂，其它大多用于自免领域。药王修美乐逐渐失势当下，JAK抑制剂被赋予下一任自免药王的重任。相对生物制剂，小分子抑制剂的生产、运输、储藏更加方便，监管机制也比较成熟，价格优势突出。因为采用口服给药方式，病人依从性高。相较于生物制剂，新上市的类似小分子JAK抑制剂在临床上展现了较生物制剂更优的的疗效，同时起效也较快。然而，由于JAK家族成员可以介导多种细胞因子的信号通路，目前已获批的JAK抑制剂就不可避免地带来一些副作用，这也就很大程度上限制了它们的临床应用范围，而这也是为什么阿布昔替尼、乌帕替尼的疗效强于达必妥（度普利尤单抗），却无法在临床上代替达必妥的原因。达必妥2023年销售额达到115.7亿美元，同比增长34%相比之下，TYK2主要通过抑制JH2假激酶结构域发挥作用，而JAK抑制剂是抑制JH1激酶结构域。通过与TYK2的JH2结构域结合，可以保持对其他JAK家族成员及整个激酶家族的高选择性。TYK2抑制剂通过选择性阻断TYK2介导的IL-23、IL-12、I型IFN等少数炎症信号通路，在发挥治疗作用的同时，对其他JAK家族成员和细胞因子通路的影响较小。这种高度选择性有助于在疗效和安全性之间取得更好平衡，降低毒副作用的风险。因此，TYK2抑制剂被认为是JAK家族最耀眼的希望。第一款TYK2抑制剂、Sotyktu的数据显示，与其他JAK抑制剂相比，Sotyktu在斑块状银屑病治疗中展现出相对优越的疗效，在感染、心血管事件等方面的风险可能较低，没有报告过严重副作用，不良事件以轻度或中度为主，最常见的是上呼吸道感染和鼻咽炎。中位复发时间可与二代生物制剂媲美。武田重金引进的TAK-279，被GlobalData预测为将是第二款获得批准的TYK2抑制剂。去年TAK-279治疗活动性银屑病关节炎的2b期研究达到主要终点，临床数据展现出了其良好的疗效，随着剂量增加疗效递增，瘙痒症状有明显改善，且各剂量组相比安慰剂没有明显增加不良事件发生率。占据First-in-Class先机的BMS还在大举扩张Sotyktu适应症范围，根据BMS官网显示，除了银屑病适应症，干燥综合征、银屑病关节炎、系统性红斑狼疮、斑秃、盘状红斑狼疮均已到后期临床阶段。BMS公司也在临床试验中探索Sotyktu用于克罗恩病等的潜力。这些布局虽然还存在不确定性，但若取得突破将极大拓展Sotyktu的市场空间。TYK2的世界才刚刚被打开。预计到2028年，全球银屑病药物市场将进一步扩容至约400亿美元，如果TYK2能继续通过大规模临床试验证明有效性和长期安全性，以及长期获益，已有的银屑病领域就足够让TYK2有跻身黄金靶点的潜力。同类最佳TYK2，会来自中国吗？值得注意的是，目前的在研TYK2管线中，中国公司占据了重要位置。尽管中国企业在JAK抑制剂市场起步较晚，2017年一代JAK抑制剂才上市，但在TYK2抑制剂研发上，国内药企并不逊色。例如Alumis的核心管线ESK-001，是海思科早前立项于2018年的项目，在BMS的TYK2抑制剂（BMS-986165）还处于3期临床时，海思科发表了基于BMS-986165发现新的临床1期候选药物的文章，呈现了一个成功的Me-too药物研发案例。2021年3月，海思科下属子公司FT集团以首付6000万美元，潜在交易1.2亿美元里程碑，将旗下在研TYK2抑制剂所属专利和权益转让给Alumis的前身公司。转让之时，其在全球的研发进展处于第三，仅次于BMS和武田。经过三年的临床研究，ESK-001展现了争夺Best-in-Class的潜力。前不久的AAD大会上，Alumis公布了2期积极数据，所有测试的5个剂量PASI75指标都达到了主要终点。最高剂量组（每天两次，40mg）中，64.1%的患者达到了这一水平的改善，而安慰剂组只有0%的患者达到了这一水平，并表现出良好的总体耐受性。国产第一梯队中，诺诚健华进度最快。依靠肿瘤起家，诺诚健华虽然仍有亏损，但手中的现金和现金等价物却高达85.8亿元。相对雄厚的资金实力，是开发自免药物的重要优势。两款TYK2产品中，ICP-332是目前临床数据最佳的中重度特应性皮炎药物之一，也是副作用最小的JAK药物之一，主要是由于ICP-332对TYK2具有强效抑制活性，对JAK2的选择性高达约400倍。ICP-488这款TYK2变构抑制剂，则是和BMS Sotyktu正面交锋，选择性结合JH2假激酶结构域，对JAK1-3无抑制活性，开发用于银屑病、银屑病关节炎、系统性红斑狼疮等。在临床1期健康受试者试验中，ICP-488已完成单剂量爬坡和多剂量爬坡研究，显示了良好的安全性和耐受性，目前已经快速推进至临床2期。不过，针对自免疾病的TYK2药物赛道已日渐拥挤。TYK2的另外探索方向，是在包括阿尔茨海默病（AD）和多发性硬化症（MS）在内的介导神经退行性疾病所涉及的潜在炎症过程中的作用。尽管MS和AD的病因和临床表现不同，但TYK2信号通路可能是一个共同的治疗靶点。抑制TYK2在MS中可阻断IL-12/IL-23介导的炎症反应，在AD中可减少Aβ诱导的神经元死亡。目前在MS和AD中有所布局的不多，但同样有国内Biotech做先锋。高光制药的TLL-041，是首个具有穿透血脑屏障能力的高选择性TYK2/JAK1抑制剂，潜在适应症包括帕金森病、阿尔茨海默病和多发性硬化症等，已在去年3月对外授权给Biohaven。高光制药获得2000万美元首付款和潜在的9.5亿美元里程碑款及销售分成，双方在全球协作进行临床开发。TLL-041预计在今年进入临床2期。能够在TYK2竞争中挖掘到CNS渗透性TYK2/JAK1，足以说明高光制药的实力。国内在研TYK2管线，整理自公开数据总体来说，国内药企在TYK2跟进迅速，第一梯队品种正在快速临床进程中，但目前国内TYK2靶点药物研发仍处于早期阶段，创新式的结构优化、差异化的结构设计来取得更优秀的TYK2抑制剂，或许能让国内玩家有同类最佳的竞争机会。BMS Sotyktu的初步商业成功，武田的重金押注，都让TYK2充满“钱景”。但还需要关注的是，TYK2的竞争对手不止是自己，既包括达必妥等成熟商业化的药物，还有其他靶点机制的强力候选药物，如强生的IL-23R拮抗多肽JNJ-2113，礼来的IL-17抑制剂DC-806等。*封面图片来源：123rf文|张珏微信|13240321829添加时请注明：姓名-公司-职位网站、公众号等转载请联系授权：Rekkiiie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

引进/卖出临床2期临床3期临床1期

2024-03-26

·BioSpace

Protagonist Therapeutics Provides Update on VERIFY Patient Enrollment and Timing of Top-line Data

On track to achieve 250 patient enrollment target in March 2024 Top-line data for 32-week primary endpoint expected in the first quarter of 2025 NEWARK, CA / ACCESSWIRE / March 26, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced it has randomized 241 patients in the ongoing Phase 3 VERIFY clinical trial evaluating rusfertide in polycythemia vera ("PV") as of today and expects to meet the trial's 250 patient enrollment target by the end of March 2024. Eligible patients in screening as of March 31, 2024 will be randomized by the end of April 2024. The Company expects to announce top-line data for the study's 32-week primary efficacy endpoint by the end of the first quarter of 2025. "Currently available therapies provide suboptimal hematocrit and symptom control in patients with PV, and we believe rusfertide has the potential to meet these unmet medical needs. We are looking forward to the results of the VERIFY phase 3 study in anticipation of filing an NDA for rusfertide in 2025 together with our partner Takeda," said Arturo Molina, M.D., M.S., Protagonist's Chief Medical Officer. "We wish to thank the principal investigators and study staff for their dedication and contributions towards completing enrollment, and the patients who have agreed to participate in this important research study." The Phase 3 VERIFY trial (NCT05210790) is a global Phase 3 randomized, double-blind, placebo-controlled trial designed to enroll approximately 250 patients. The trial evaluates the efficacy, symptom burden and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy dependent despite standard of care treatment. The trial enrolled patients in 20 countries across North and South America, Europe, Asia and Australia. This Phase 3 study along with the REVIVE Phase 2 trial and other completed studies will comprise the clinical data package planned for NDA filing. "2024 has been a very busy year for the rusfertide program, and we are pleased to announce our Phase 3 VERIFY trial is advancing as planned," said Dinesh V. Patel, Ph.D., the Company's President and CEO. "Rusfertide has performed very well in the Phase 2 REVIVE study as further confirmed by the long-term follow-up data showing the durability of hematocrit control. We look forward to data from the 52-week endpoint for VERIFY including the durability of response in the first half of 2025, and potentially filing an NDA in the fourth quarter of 2025. Dr. Patel continued, "We are in a very exciting phase for the Company as we anticipate a series of announcements and data disclosures in the second half of 2024 and throughout 2025, centering on our late stage partnered assets, as well as our fully owned discovery programs like Oral IL-17 antagonist, and other programs in hematology and metabolic diseases." About Protagonist Protagonist Therapeutics is a biopharmaceutical company with peptide-based new chemical entities (NCEs) rusfertide and JNJ-2113 (formerly PN-235) in advanced Phase 3 stages of clinical development, both derived from the Company's proprietary technology platform. Protagonist and JNJ scientists jointly discovered PN-235 (now known as JNJ-2113) as part of Protagonist's Interleukin-23 receptor (IL-23R) collaboration with JNJ and followed it through IND-enabling pre-clinical and Phase 1 studies, with JNJ assuming responsibility for further clinical development. Rusfertide, a mimetic of the natural hormone hepcidin, is the Company's lead drug candidate currently in a global Phase 3 development program. The randomized portion of the Phase 2 REVIVE study has been successfully completed, and results were published in The New England Journal of Medicine in February 2024. The open-label extension component of Phase 2 is ongoing, as is the global Phase 3 VERIFY study of rusfertide in polycythemia vera. Rusfertide is being co-developed and co-commercialized with Takeda pursuant to a worldwide collaboration and license agreement with Takeda announced in January 2024. More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at . Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential clinical benefits of rusfertide, the timing of top-line data and other data disclosures. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreement with Johnson & Johnson, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release. Investor Relations Contact Corey Davis, Ph.D. LifeSci Advisors +1 212 915 2577 cdavis@lifesciadvisors.com Media Contact Virginia Amann, Founder/CEO ENTENTE Network of Companies virginiaamann@ententeinc.com SOURCE: Protagonist Therapeutics, Inc. View the original press release on accesswire.com

临床3期临床2期申请上市引进/卖出临床1期

2024-03-19

·医药观澜

今日，荃信生物将在港交所正式上市！

▎药明康德内容团队报道根据荃信生物近日在港交所发布的公告，该公司将于今日（3月20日）在港交所正式上市。荃信生物创办于2015年，专注于开发治疗自身免疫性疾病及过敏性疾病的生物疗法。截图来源：荃信生物招股书根据荃信生物招股书，该公司的产品管线涵盖了自身免疫和过敏性疾病的四个主要领域，包括皮肤、风湿、呼吸道及消化道疾病。该公司有两个核心产品——IL-17A抑制剂QX002N、抗IL-4Rα单抗QX005N，它们目前分别处于3期和2期临床研究阶段。此外，该公司还有其它七种候选药物处于不同的研究阶段。以下根据荃信生物的招股书分享该公司的部分产品管线信息，仅供读者参阅。QX002N是一种靶向IL-17A的高亲和力单克隆抗体。IL-17A在各种自身免疫性疾病的发病机制中起着关键作用，IL-17A抑制剂已经获现行的临床指南推荐，用于接受一线传统治疗后仍有高疾病活动度的强直性脊柱炎（AS）患者的二线单独治疗方法。荃信生物已经在中国启动QX002N治疗AS的3期临床试验，预计在2025年下半年完成。QX002N此前已在治疗AS的1b期及2期临床试验中显示出良好疗效。在1b期临床试验中，每2周接受一次QX002N (160mg）的受试者，第16周的国际脊柱关节炎评估协会20反应标准（ASAS20定义为较ASAS评分基线改进20%）及ASAS40（定义为较ASAS评分基线改进40%）应答率分别为62.5%、37.5%。在2期临床试验中，每4周一次接受QX002N (160mg）的受试者在第16周时的ASAS20及ASAS40应答率分别达到60.0%和40.0%。▲荃信生物产品管线（截图来源：荃信生物招股书）QX005N是一种阻断IL-4Rα的单克隆抗体。IL-4Rα是一种经过临床验证的靶点，由于IL-4Rα控制IL-4及IL-13的信号传导，这对于2型炎症的发生至关重要。目前，QX005N已获得7项IND批准，分别用于治疗成人特应性皮炎（AD）、青少年AD、结节性痒疹、慢性鼻窦炎伴鼻息肉（CRSwNP）、慢性自发性荨麻疹、哮喘及慢性阻塞性肺病，并已在中国启动用于AD、结节性痒疹及CRSwNP的2期临床试验。2024年1月，该产品针对成人中重度结节性痒疹适应症已经被中国国家药监局药品审评中心（CDE）纳入突破性治疗品种。QX005N已经在1a期及1b期临床试验中显示出对治疗特应性皮炎具良好的安全性及疗效。在中重度特应性皮炎患者的1b期临床试验中，300mg和600mg组于第12周中有75.0%的受试者达到湿疹面积及严重程度指数-75（EASI-75）反应，而50.0%的受试者达到研究者整体评估（IGA）分数（0或1），且没有明显增加安全风险。除了上述两款核心产品，荃信生物还有其他7款在研产品，分别为：QX001S，一款乌司奴单抗生物类似药，由荃信生物与华东医药全资子公司中美华东合作开发。该产品在中国的上市申请已经于2023年8月获CDE受理。乌司奴单抗通过抑制IL-12/IL-23共有P40亚单位发挥作用，其原研产品已经在中国获批治疗成人及儿童中重度斑块状银屑病。在针对银屑病的3期临床试验中，QX001S显示出与乌司奴单抗原研产品相当的临床疗效、安全性、免疫原性及PK特性。QX004N，一款IL-23p19抑制剂。通过与IL-23的p19亚基结合，QX004N阻断IL-23与IL-23R之间的结合以及相应的信号转导，从而抑制Th17细胞的发育并导致IL-17细胞因子的产生减少。该产品目前正在被开发用于治疗银屑病和克罗恩病。QX006N，一种IFNAR1靶向单抗，正在开发用于治疗系统性红斑狼疮（SLE）。干扰素α/β受体亚基1（IFNAR1）是一种经临床验证的治疗SLE的潜力靶点。QX006N已经在1a期临床试验中显示出良好的安全性。QX008N，一种靶向TSLP的人源化IgG1单克隆抗体，为治疗中重度哮喘和中重度慢性阻塞性肺病而研发。在1a期临床试验中，QX008N已表现出良好的安全性。据悉，荃信生物已经启动该产品治疗中重度哮喘成年患者的1b期临床试验，其余部分将由授权合作伙伴健康元完成。QX007N，一种靶向IL-33的人源化IgG1单克隆抗体。IL-33是IL-1家族成员之一。QX007N已经于2024年2月在中国获批临床，拟用于治疗慢性阻塞性肺病及哮喘。QX013N，一种靶向c-kit（一种III型受体酪氨酸激酶）的人源化IgG1 mAb，适用于治疗慢性自发性荨麻疹。2024年2月，荃信生物已经向CDE提交该产品的IND申请。QX010N，一种靶向IL-31R的人源化IgG1 mAb，适用于治疗瘙痒症。该产品目前正处于临床前研究阶段。根据荃信生物招股书介绍，该公司计划短期内聚焦推进广泛药物管线，以皮肤病作为优先切入口，同时推进风湿病、呼吸道疾病及消化道疾病候选药物。荃信生物还将与其它医药公司展开商业化合作，并寻求在国际范围内的商业化机会，加快产品惠及全球患者。参考资料：[1]02509-荃信生物-B-新上市. Retrieved Mar 18，2024, from https://data.eastmoney.com/notices/detail/02509/AN202403181626959108.html[2]荃信生物招股书. from https://www1.hkexnews.hk/listedco/listconews/sehk/2024/0312/2024031200008_c.pdf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「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。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。

临床2期临床申请临床1期临床3期临床结果