Rocatinlimab

-- Early Proof-of-Concept Results from the Phase 1a Trial Anticipated in Q3 2025 -- BOSTON--(BUSINESS WIRE)--Jan. 23, 2025-- Astria Therapeutics, Inc. (NASDAQ:ATXS), a biopharmaceutical company focused on developing life-changing therapies for allergic and immunologic diseases, today announced initiation of a Phase 1a clinical trial of STAR-0310 in healthy subjects. STAR-0310, a high affinity monoclonal antibody OX40 antagonist that incorporates YTE technology, is in development for the potential treatment of atopic dermatitis (AD) and potentially other indications. The Phase 1a trial is intended to assess the safety, tolerability, pharmacokinetics, and immunogenicity of STAR-0310 in healthy adult participants. Astria expects early proof-of-concept results from the Phase 1a trial in the third quarter of 2025. “The Phase 1a trial of STAR-0310 in healthy subjects is an important opportunity for us to clinically differentiate the profile of STAR-0310,” said Jill C. Milne, Ph.D., Chief Executive Officer at Astria Therapeutics. “We believe STAR-0310 will be the best-in-class therapy due to efficacy, safety and tolerability, and treatment burden, and could transform lives for many people living with moderate-to-severe AD.” The Phase 1a randomized, double-blind, placebo-controlled single ascending dose trial is evaluating the safety, tolerability, pharmacokinetics, and immunogenicity of STAR-0310 in approximately 40 healthy adult participants. Preclinical results support the potential for STAR-0310 to have the best-in-class OX40 inhibitor profile. By design, there is significantly less antibody-dependent cellular cytotoxicity (ADCC) with STAR-0310 compared to rocatinlimab, an OX40 antagonist currently in Phase 3 development for the treatment of AD. Reduction in ADCC activity has the potential for a more favorable safety profile and potentially wider therapeutic window for STAR-0310, which we believe provides the potential to drive more efficacy. STAR-0310 exhibits a long mean half-life of 26 days in cynomolgus monkeys, compared to 10-14 days in a typical non-half-life extended IgG1 antibody, and has comparable potency to rocatinlimab. About Astria Therapeutics: Astria Therapeutics is a biopharmaceutical company, and our mission is to bring life-changing therapies to patients and families affected by allergic and immunologic diseases. Our lead program, navenibart (STAR-0215), is a monoclonal antibody inhibitor of plasma kallikrein in clinical development for the treatment of hereditary angioedema. Our second program, STAR-0310, is a monoclonal antibody OX40 antagonist in clinical development for the treatment of atopic dermatitis. Learn more about our company on our website, www.astriatx.com, or follow us on Instagram @AstriaTx and on Facebook and LinkedIn. Forward Looking Statements: This press release contains forward-looking statements within the meaning of applicable securities laws and regulations including, but not limited to, statements regarding: the expected timing of receipt of early proof of concept results from STAR-0310 Phase 1a trial; the aims and objectives of the STAR-0310 Phase 1a trial; the development of STAR-0310 as a potential treatment for AD and potentially other indications; the potential therapeutic benefits of STAR-0310 as a treatment for AD, including its potential best-in-class profile and the potential attributes of STAR-0310 that would give it such a profile; and our corporate strategy and vision, including our mission to bring life-changing therapies to patients and families affected by allergic and immunologic diseases. The use of words such as, but not limited to, “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “goals,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” or "vision," and similar words and expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Astria’s current beliefs, expectations and assumptions regarding the future of its business, future plans and strategies, future financial performance, results of pre-clinical studies and clinical trials of Astria’s product candidates and other future conditions. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks and uncertainties related to: changes in applicable laws or regulations; the possibility that we may be adversely affected by other economic, business, and/or competitive factors; risks inherent in pharmaceutical research and development, such as: adverse results in our drug discovery, preclinical and clinical development activities, the risk that the results of preclinical studies may not be replicated in clinical trials, that the preliminary, initial or interim results from clinical trials may not be indicative of the final results, that the results of early stage clinical trials, such as the results from the ALPHA-STAR Phase 1b/2 clinical trial, may not be replicated in later stage clinical trials, such as the ALPHA-ORBIT trial and the open-label extension trial, the risk that we may not be able to enroll sufficient patients in our clinical trials on a timely basis, and the risk that any of our clinical trials, including ALPHA-ORBIT, may not commence, continue or be completed on our anticipated timelines, or at all; decisions made by, and feedback received from, the FDA and other regulatory authorities on our clinical trial design, including for ALPHA-ORBIT, and on our regulatory and clinical trial submissions, including receipt of FDA minutes from our December 2024 end of Phase 2 meeting, and other feedback from potential clinical trial sites, including investigational review boards at such sites, and other review bodies with respect to navenibart, STAR-0310, and any other future development candidates, decisions that we make about the design of clinical trials in response to regulatory feedback, including the design of the ALPHA-ORBIT trial and the long-term extension trial; our ability to manufacture sufficient quantities of drug substance and drug product for navenibart, STAR-0310, and any other future product candidates on a cost-effective and timely basis, and to develop dosages and formulations for navenibart, STAR-0310, and any other future product candidates that are patient-friendly and competitive; our ability to develop sufficient data to enable the use of planned devices with navenibart, STAR-0310 and any other future product candidates at commercial launch or otherwise as planned; our ability to develop biomarker and other assays, along with the testing protocols therefor; our ability to obtain, maintain and enforce intellectual property rights for navenibart, STAR-0310 and any other future product candidates; our potential dependence on collaboration partners; competition with respect to navenibart, STAR-0310, or any of our other future product candidates; the risk that survey results, modeling data and market research may not be accurate predictors of the commercial landscape for HAE, the ability of navenibart to compete in HAE and the anticipated position and attributes of navenibart in HAE based on clinical data to date, its preclinical profile, pharmacokinetic modeling, market research and other data; risks that any of our clinical trials of STAR-0310 may not commence, continue or be completed on time, or at all; risks that results of preclinical studies of STAR-0310 will not be replicated in clinical trials; our ability to manage our cash usage and the possibility of unexpected cash expenditures; our ability to obtain necessary financing to conduct our planned activities and to manage unplanned cash requirements; the risks and uncertainties related to our ability to recognize the benefits of any additional acquisitions, licenses or similar transactions; and general economic and market conditions; as well as the risks and uncertainties discussed in the “Risk Factors” section of our Annual Report on Form 10-K for the period ended December 31, 2023 and in other filings that we may make with the Securities and Exchange Commission. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Astria may not actually achieve the forecasts or expectations disclosed in our forward-looking statements, and investors and potential investors should not place undue reliance on Astria’s forward-looking statements. Neither Astria, nor its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Astria’s views as of any date subsequent to the date hereof. View source version on businesswire.com: https://www.businesswire.com/news/home/20250123072294/en/ Astria Contact: Investor Relations and Media: Elizabeth Higgins investors@astriatx.com Source: Astria Therapeutics, Inc.

2024年12月23日，RAPT Therapeutics宣布引进，处于中国二期临床研究阶段的，济民可信长效IgE抗体JYB1904的大中华区外全球权益，RAPT Therapeutics支付3500万美元预付款，最高6.725亿美元里程碑金额，以及一定比例的销售分成，协议总金额7.075亿美元。 同日，创响生物和美国Ikena Oncology合并，合并后的公司将专注于开发下一代的OX40抗体IMG-007的开发。IMG-007与处于2期临床和后期开发的其他OX40靶向单克隆抗体相比，IMG-007的半衰期更长，使其具有优化剂量和时间表的潜力。 此外，IMG-007具有沉默的抗体依赖性细胞毒性（ADCC）功能，并且是非T细胞耗竭的，与该类其他单克隆抗体相比，其耐受性可能得到改善。IMG-007治疗特应性皮炎的2b期临床试验预计将于2025年初开始。 圣诞节前公布的两则关于自免药物半衰期延长的项目消息，也成为今年自免领域火热进展的缩影，从此前th2到th17通路，新靶点不断地情况下，传统靶点的迭代药物成为热点，半衰期延长、双抗和口服成为新的自免研发思路。 半衰期延长方面，LS和YTE突变是最长的技术平台之一，特别是YTE突变技术已经在多个自免项目中得到验证，半衰期均可以达到60天以上，多个公司采用该技术进行迭代药物开发。 Apogee此前多个项目在临床及临床阶段均验证YTE平台技术优势，对于IL-4R抗体药物的半衰期提高了5倍以上。 截止到目前，根据umabsDB数据库的记录，超过二十多款药物采用了YTE突变技术，4款药物已经获批，最长半衰期达到100多天，同时多款药物处于临床阶段。 除了提高依从性，疗效提高也至关重要，特别是如OX40及TL1A等热门靶点的疗效并没有显著提升，双抗成为其下一代的药物的开发出口。 2024年9月25日，安进公布自免/炎症领域最新临床进展，包括OX40抗体Rocatinlimab治疗特应性皮炎的三期临床前线数据。HORIZON研究达到主要终点，Rocatinlimab和安慰剂组的EASI-75响应率分别为32.8%和13.7%，Rocatinlimab和安慰剂组的vIGA-AD 0/1的响应率为19.3%和6.6%(不及预期：安进公布OX40抗体特应性皮炎三期临床数据)。 vIGA-AD 0/1的响应率来看，不仅显著低于Rocatinlimab在2021年公布的2期临床16W的数据，同时也低于Sanofi同类抗体 Amlitelimab二期临床的数据，可以说不及预期。 中至重度的特应性近年来的生物制剂疗法进展显著，Sanofi的IL-4R抗体DUPIXENT最早打破僵局，随后IL-13相关抗体目前成为最近疗法，此外如OX40L、IL-22R、IL-31R、TSLP和IL-22等其它靶点的药物还未显示更加疗效，期待后续相关药物或者双抗迭代药物的进展。 TL1A同样如此，12月17日，Sanofi和Teva公布了合作开发的TL1A抗体Duvakitug（TEV-574）的Phase 2b临床RELIEVE UCCD的初步结果，虽然高剂量组TEV-574的48%内镜响应率改善高于历史水平，但是本次安慰剂组20%+的临床缓解率同样远远超出了历史上所有其他试验的安慰剂组水平，使得其临床结果有些黯然失色，经安慰剂修正后就成了泯然众人的27%，就算在现有三个TL1A分子中也只略占上风，甚至就还比不上Infliximab和Upadacitinib了。 单靶点的疗效不佳显然让相关双抗药物成为新的机会，此前在TSLP和IL-33等多种药物方面sanofi已经先行进行临床开发，康诺亚等多种公司也在跟进相同策略（TSLP/IL-13：康诺亚NewCO的一款双抗浮出水面），博奥信也开发了IL-4R/TSLP双抗（大涨53%：中国资产再次拯救美股biotech）。 除了双信号通路双抗，CD3相关的TCE双抗拓展至B细胞相关的自免疾病治疗显然一度成为下半年BD的主旋律，短短成立半年的Candid甚至在三个月内扫货五款药物，多个CD19、CD20和BCMA相关TCE双抗转型自免，甚至已经迭代到三抗药物（3亿美金首付款：GSK收购恩沐CD19/CD20/CD3三抗）。 然而值得注意的是，目前TCE应用于自免领域仍有不少调整，相关验证的临床数据也不够多（新英格兰：BCMA/CD3双抗Teclistamab在自免疾病中的治疗探索），未来仍需要进行更多探索。 最后，在依从性的竞争迭代方面，口服一度是大分子药物的缺陷，但是近期Sorriso Pharmaceuticals公布了其TNFα/IL-23双抗SOR102，在针对溃疡性结肠炎（UC）患者的1b期临床试验中的积极结果。这是首次成功证明口服抗体能够产生临床疗效，有潜力为溃疡性结肠炎患者提供一种有效且便捷的口服治疗选择。 由于肠道环境恶劣，口服的大分子蛋白质通常会在肠道内失效。Sorriso成功的秘诀在于这些抗体的大小约为单克隆抗体的十分之一，并且经过工程设计，能够抵抗许多使大分子化合物难以发挥作用的蛋白酶。研究人员还使用了一种特殊的氨基酸连接子连接TNF-α和IL-23抗体，这种连接子在接触胰蛋白酶（一种遍布消化道的酶）时会裂解。 所以当它们结合在一起时协同发挥作用，但彼此分离时也能同样有效地发挥作用。这种双重靶向的方法可能通过同时阻断炎症性肠病的不同发病机制来提高疗效，且通过在炎症组织内局部提供联合治疗，全身暴露量极小。该技术平台源自对一家名为VHsquared的英国生物技术公司的收购，该公司一直在研究口服肠道限制性抗体。 全球自免领域超过2000亿美金的市场，同时还有多个适应症被不断挖掘，使得多个临床未满足的疗法得到应有场景，相关药物的市场开发潜力巨大。 共建Biomedical创新生态圈！ 如何加入BiG会员？