Grapiprant

根据思路迪医药（3D Medicines）近日公告，该公司将于今日（12月15日）在港交所正式上市。思路迪医药是一家专注肿瘤治疗领域的生物医药公司，核心产品恩沃利单抗（一款皮下注射PD-L1抗体）已实现商业化。根据招股书，此次思路迪医药在港交所上市，基石投资者有徐州经开区（香港）、Harvest、TradArt Investment SP、Mobilewise。截图来源：参考资料[2]思路迪医药成立于2014年，致力于为癌症患者，尤其是那些需要长期治疗的患者研发肿瘤药物。该公司的核心业务模式是通过联合合作开发、许可引进及自主发现等方式，开发及商业化肿瘤产品及候选药物。目前，思路迪医药已建立一条包含1款核心产品及11款候选药物的管线，其中核心产品恩沃利单抗已在中国获批，另有7款候选药物处于临床阶段。 恩沃利单抗（商品名：恩维达）是一款PD-L1单域抗体融合蛋白，由康宁杰瑞发现及开发。该产品的肿瘤适应症临床开发由思路迪医药负责，其在中国大陆的商业化推广由先声药业负责。据招股书介绍，该产品体积更小，稳定性更好，溶解度更高，使高浓度制剂适合进行皮下注射。2021年11月，恩沃利单抗获得中国国家药监局（NMPA）附条件批准，用于治疗既往接受过治疗的微卫星高度不稳定（MSI-H）/错配修复功能缺陷（dMMR）晚期实体瘤。 除了已获批适应症，恩沃利单抗用于治疗晚期胃或胃食管交界处腺癌（G/GEJ）的适应症已在中国完成探索性2期临床试验，治疗晚期胆道癌的适应症正在进行中国关键性3期临床试验，治疗选定类型晚期肉瘤的适应症正在美国进行关键性2期临床试验（由思路迪医药合作伙伴TRACON公司发起）。此外，恩沃利单抗还获得美国FDA授予两项孤儿药资格，分别用于治疗晚期胆道癌和软组织肉瘤。 ▲思路迪医药产品管线（截图来源：参考资料[2]） 3D189是一款多肽抗癌疫苗，思路迪医药拥有在大中华区所有适应症的独家开发及商业化权利。它靶向一种名为Wilms瘤1（WT1）的蛋白，该蛋白在一系列血液恶性肿瘤及实体瘤中存在并过度表达。通过联合治疗，3D189有潜力靶向过度表达WT1的超20种癌症，且因其能诱导强烈的T细胞免疫应答的能力，该产品被设计用于预防及延缓复发及有望延长该等患者的生存期。此前，它已在治疗急性髓系白血病（AML）适应症上获得FDA授予快速通道资格和孤儿药资格。2022年3月，3D189在中国获得临床试验批准，思路迪医药计划与其合作伙伴SELLAS集团共同参与国际多中心临床试验。 3D229是一种高亲和力的可溶性Fc融合蛋白，旨在结合生长停滞特异性蛋白6（GAS6），拦截GAS6与其受体AXL的结合来阻断GAS6AXL信号通路的激活。该产品由Aravive公司开发，思路迪医药获得了其在大中华区肿瘤领域的独家开发和商业化权利。在中国，该产品正在进行一项铂耐药性卵巢癌（PROC）二线治疗的3期国际多中心临床试验，另外其针对非小细胞肺癌/肾细胞癌/尿路上皮癌患者的1b/2期临床试验也已获得批准。3D011是思路迪医药自主发现的一款酪氨酸激酶抑制剂（TKI）前药，由多靶点抗血管生成TKI试验药物ABT-869和特异性五肽（Asp-Glu4）通过连接臂连接而成。 药效学研究结果显示，3D011能够显著地抑制肿瘤生长；安全药理研究中，它对hERG通道没有抑制作用。目前，思路迪医药正在晚期恶性实体瘤患者中开展一项开放标签、单臂1期剂量递增及剂量扩展临床试验。3D185是一款成纤维细胞生长因子受体（FGFR）1-3及集落刺激因子1受体（CSF1R）抑制剂，有望与PD-L1单抗恩沃利单抗联合使用。通过与海和药物及中国科学院上海药物研究所订立许可协议，思路迪医药拥有3D185在全球范围内独家开发、生产及商业化用于治疗肿瘤和肺纤维化的权利。2021年8月，该产品已在中国和美国完成针对晚期实体瘤患者的1期临床试验。目前，3D185的一种新剂型正在进行一项1期临床试验研究。3D1001是一款第三代环氧化酶-2（COX-2）抑制剂，因其良好的PK特性，在临床研究中起效快且可长时间缓解术后牙痛患者的疼痛。通过与海和药物订立许可协议，思路迪医药拥有3D1001在中国疼痛适应症领域独家开发、生产及商业化的权利。思路迪医药计划开发3D1001用于治疗术后牙痛及癌症疼痛等其他潜在疼痛适应症，目前中国1/2期临床试验正在筹备中。3D1002是一款E型前列腺素受体4（EP4）受体拮抗剂。在1/2期临床研究中，该产品已显示出良好的安全性特征及具前景的疗效结果。通过与海和药物订立许可协议，思路迪医药拥有3D1002在中国疼痛适应症领域独家开发、生产及商业化的权利。思路迪医药计划开发3D1002用于治疗癌症疼痛及骨关节炎，目前中国2期临床试验正在准备中。3D197是一款新一代全人抗CD47 IgG4单克隆抗体。 CD47 IgG4单抗是人体免疫球蛋白G中的一种，是血液循环中常见的抗体类型，在对抗入侵病原体的抗体基础免疫中起着重要作用。通过与ImmuneOncia公司订立独家许可协议，思路迪医药拥有3D197在大中华区肿瘤适应症方面独家开发、生产及商业化的权利。2022年1月，该产品在中国获得临床试验批准。除了上述处于临床阶段的候选药物外，思路迪医药也正在评估管线中多款临床前阶段的候选药物，包括：1）靶向T细胞CD3受体及肿瘤细胞PD-L1的双特异性抗体药物3D057；2）靶向血液恶性肿瘤及实体瘤中WT1蛋白的新一代免疫疗法3D059；3）靶向肿瘤细胞的Semaphorin 4D（Sema4D）单克隆抗体3D060；4）针对KRAS突变患者的小分子3D062等。根据思路迪医药招股书，此次IPO募集资金90%将用于在研产品和候选药物的研发、监管备案及商业化。未来，该公司计划：进一步扩展恩沃利单抗的商业潜力及探索市场机会；加快产品开发以进行商业化及进一步丰富研发管线；进一步增强内部创新研发能力；进一步培养GMP制造能力，加强商业化能力；继续吸引、栽培及留住人才等。 参考文献：[1]01244-3D MEDICINES-B-新上市 .Retrieved Dec 13, 2022. From https://data.eastmoney.com/notices/detail/01244/AN202212131581041400.html[2] 3D Medicines招股书.Retrieved Nov 29 , 2022. From https://pdf.dfcfw.com/pdf/H2_AN202211291580645617_1.pdf?1669706740000.pdf 内容来源于网络，如有侵权，请联系删除。

Novel best-in-class MEK-RAF complex inhibitor IK-595 targets RAS pathway; IND in 2023 Novel paralog-selective TEAD inhibitor IK-930 advancing as planned in dose escalation; clinical data in 2023 Company prioritizes advancement of targeted oncology portfolio; cash runway extended into 2025 BOSTON, Nov. 28, 2022 (GLOBE NEWSWIRE) -- Ikena Oncology, Inc. (Nasdaq: IKNA, “Ikena”), a targeted oncology company forging new territory in patient-directed cancer treatment, today announced a next-generation mitogen-activated protein kinase (MEK)-RAF complex inhibitor, IK-595, has been nominated as the company’s first development candidate in the RAS pathway. The RAS pathway is implicated in at least half a million new cancer diagnosis each year in the United States alone. Ikena aims to target the pathway on multiple levels, including preventing known resistance mechanisms to achieve deep and sustained responses. Ikena’s new development candidate, IK-595, traps MEK and RAF in an inactive complex, more completely inhibiting RAS signals than existing inhibitors. IK-595's ability to complex CRAF, in particular, prevents a well-recognized signaling bypass mechanism that cancer cells employ to drive therapeutic resistance to other drugs in this class. In addition, trapping CRAF in an inactive complex prevents the kinase independent anti-apoptotic function in RAS and RAF mutant cancers, a mechanism that cannot be addressed with first generation MEK inhibitors or pan-RAF inhibitors. IK-595 is being developed as an oral therapy, with a half-life enabling a pharmacokinetic profile potentially superior to other drugs, with the goal of developing an optimal therapeutic window for patients. The company plans to submit an investigational new drug application (IND) for IK-595 to the US Food & Drug Administration (FDA) in the second half of 2023. “I am thrilled to announce this addition to our pipeline, one that adds to our holistic approach to the Hippo & RAS oncosignaling network. IK-595 inhibits multiple nodes of MEK-RAF signaling, including avoiding known mechanisms of resistance,” said Mark Manfredi, PhD, Ikena’s Chief Executive Officer. “The industry’s excitement about MEK inhibition stems from its great potential as a target, but the challenges of CRAF bypass and achieving optimal target inhibition have kept first generation treatments from meeting the full potential of the target. We are hopeful that our MEK-RAF trapping approach with an optimized therapeutic window can make IK-595 a game-changing candidate for multiple indications in the RAS space.” Development Highlights, Corporate Updates, and Upcoming Milestones Advancing new development candidate, IK-595, through IND-enabling studies, targeting MEK-RAF through novel mechanisms aiming to address existing gaps in the MEK inhibitor space Preclinical differentiation data planned for presentation in the first half of 2023IND targeted in the second half of 2023 Progressing novel, paralog-selective transcriptional enhanced associate domain (TEAD) inhibitor, IK-930, in the clinic and further defining differentiation profile from panTEAD inhibition Monotherapy program progressing as planned, advanced through multiple dose escalation cohortsPreclinical data on differentiation and advantages of paralog selectivity planned for presentation in first half of 2023Initiation of osimertinib combination cohort clinical program expected in first half of 2023Initial clinical data from IK-930 monotherapy program expected in second half of 2023 Following a portfolio review, discontinuing the internal clinical development of the EP4 antagonist IK-007 and exploring strategic alternatives for this program Clinical data from IK-007 in microsatellite stable colorectal cancer (MSS-CRC) will be presented in a poster at 2022 European Society for Medical Oncology Immuno-Oncology Congress Portfolio reprioritization and streamlining of discovery and clinical activities contribute to extension of cash runway into 2025 Runway does not include any potential licensing revenue from the aryl hydrocarbon receptor (AHR) antagonist IK-175 program, currently in development in collaboration with Bristol Myers Squibb and eligible for opt-in through early 2024 “Ikena has a strong track record of internal drug discovery and development that has built our robust clinical and early-stage pipeline,” said Jotin Marango, MD, PhD, Chief Financial Officer and Head of Corporate Development of Ikena. “Our goal is to continue our leadership in targeted oncology by discovering and advancing best-in-class candidates like IK-930 and IK-595, therapies designed to address the needs of specific patient populations while at the same time building value for our shareholders.” About Ikena OncologyIkena OncologyTM is focused on developing differentiated therapies for patients in need that target nodes of cancer growth, spread, and therapeutic resistance in the Hippo and RAS onco-signaling network. The Company’s lead targeted oncology program, IK-930, is a paralog-selective TEAD inhibitor addressing the Hippo signaling pathway, a known tumor suppressor pathway that also drives resistance to multiple targeted therapies. The Company’s additional research spans other targets in the Hippo pathway as well as the RAS signaling pathway, including developing IK-595, a novel MEK-RAF inhibitor. Additionally, IK-175, an AHR antagonist, is being developed in collaboration with Bristol Myers Squibb. Ikena aims to utilize their depth of institutional knowledge and breadth of tools to efficiently develop the right drug using the right modality for the right patient. To learn more, visit www.ikenaoncology.com or follow us on Twitter and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding: the timing and advancement of our targeted oncology programs, including the timing of updates; our expectations regarding the therapeutic benefit of our targeted oncology programs; our ability to efficiently discover and develop product candidates; our ability to obtain and maintain regulatory approval of our product candidates; the implementation of our business model, and strategic plans for our business and product candidates. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of our targeted oncology programs; our expectations regarding the therapeutic benefit of our targeted oncology programs; expectations regarding our new executive officer; our ability to efficiently discover and develop product candidates; the implementation of our business model, and strategic plans for our business and product candidates, and other factors discussed in the “Risk Factors” section of Ikena’s Form 10-Q for the quarter ended September 30, 2022, which is on file with the SEC, as updated by any subsequent SEC filings. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements. Investor Contact:Rebecca CohenIkena Oncologyrcohen@ikenaoncology.com Media Contact:Gwen SchankerLifeSci Communicationsgschanker@lifescicomms.com