Inlexisertib

– MOTION Phase 3 Data Demonstrate Robust Efficacy, Clinically Meaningful Improvements in Quality-of-Life Measures, and Well-Tolerated Safety Profile, Positioning Vimseltinib as Potential New TGCT Treatment – – Company Expects to Submit a New Drug Application (NDA) in the Second Quarter of 2024 and Marketing Authorisation Application (MAA) in the Third Quarter of 2024 – WALTHAM, Mass.--(BUSINESS WIRE)-- Deciphera Pharmaceuticals LLC, (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, today announced that results from the Company’s MOTION pivotal Phase 3 study of vimseltinib in patients with TGCT are being highlighted in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Chicago, Illinois, and have been published in The Lancet. The article titled “Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a randomised phase 3 trial” is now available online and will be published in a future print issue of The Lancet. “The results from the MOTION pivotal Phase 3 study provide compelling evidence that vimseltinib can address the unmet medical need in TGCT for an effective and well-tolerated therapy without cholestatic hepatotoxicity,” said Hans Gelderblom, M.D., Ph.D., Chair of the Department of Medical Oncology at Leiden University Medical Center and senior author of the manuscript. “In addition to its robust antitumor activity and tolerability, vimseltinib also demonstrated clinically significant functional and symptomatic improvements in key quality-of-life measures, which can provide long-term, meaningful benefits to TGCT patients.” “Building upon the strong efficacy results disclosed previously at topline, we are excited to share details on the statistically significant and clinically meaningful improvements that vimseltinib offered TGCT patients across all six key secondary endpoints, along with its favorable safety profile,” said Matthew L. Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. “We remain on track to submit an NDA for vimseltinib in the second quarter of 2024, and an MAA in the third quarter of 2024, and look forward to bringing this important new therapy to TGCT patients globally.” In addition to the results from the MOTION pivotal Phase 3 study, the Company will also be presenting a trial-in-progress poster for the ongoing Phase 1/2 study of DCC-3116 in combination with ripretinib at the 2024 ASCO Annual Meeting. Both presentations are available on the Company’s website at . Presentation details are as follows: Abstract Number: 11500 Title: Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with tenosynovial giant cell tumor: Results from the phase 3 MOTION trial. Presenter: William D. Tap, M.D., FASCO, Memorial Sloan Kettering Cancer Center Presentation Date: Monday, June 3, 2024 Presentation Time: 3:00 – 3:12 PM CT Key Highlights: Study Design: The MOTION pivotal Phase 3 study is a two-part, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed). In Part 1, patients (n=123) were randomized two-to-one to receive either 30 mg twice weekly of vimseltinib (n=83) or placebo (n=40) for 24 weeks. The results for Part 1 of the study are based on a data cutoff date of August 22, 2023. The open-label Part 2 portion of MOTION, in which patients from both the vimseltinib and placebo arms receive treatment with vimseltinib, remains ongoing. ORR: The primary endpoint of the study is ORR at Week 25 as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent radiologic review (IRR). The study met its primary endpoint in the intent-to-treat (ITT) population demonstrating statistically significant and clinically meaningful improvement versus placebo in ORR at Week 25 based on IRR per RECIST v1.1. In the ITT population, the ORR at Week 25 was 40% (95% CI: 29%, 51%) for the vimseltinib arm and 0% (95% CI: 0%, 9%) for the placebo arm resulting in a response difference (vimseltinib versus placebo) of 40% (95% CI: 29%, 51%) (p<0.0001). Secondary Endpoints: In addition to meeting the primary endpoint, the study also achieved statistically significant and clinically meaningful improvements versus placebo in all six key secondary endpoints assessed at Week 25 including ORR by tumor volume score (TVS), active range of motion (ROM), physical function, stiffness, quality of life, and pain. ORR by TVS: The ORR at Week 25 based on IRR per TVS was 67% (95% CI: 56%, 77%) for the vimseltinib arm and 0% (95% CI: 0%, 9%) for the placebo arm (p<0.0001). Active ROM: Treatment with vimseltinib demonstrated an improvement in mean change from baseline in active ROM at Week 25 of 18.4% versus a 3.8% improvement for placebo (p=0.0077). Physical Function by PROMIS-PF: Treatment with vimseltinib demonstrated an improvement in mean change from baseline in PROMIS-PF at Week 25 of 4.6 versus 1.3 for placebo (p=0.0007). Worst Stiffness Numeric Rating Scale (NRS): Patients treated with vimseltinib reported a decrease of 2.1 versus 0.3 for placebo in worst stiffness (p<0.0001). Quality of Life by EuroQol Visual Analogue Scale (EQ-VAS): The mean change from baseline for EQ-VAS was significantly higher with 13.5 in the vimseltinib arm versus 6.1 in the placebo arm (p=0.016). Brief Pain Inventory (BPI) Worst Pain Response Rate: The BPI worst pain response rate was 48% for patients receiving vimseltinib versus 23% for placebo (p=0.0056). Safety and Tolerability: Vimseltinib was well tolerated with most treatment-emergent adverse events (TEAEs) were grade 1 or 2. There was no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair hypopigmentation. Serum enzyme elevations were consistent with the known mechanism of action of CSF1R inhibitors. TEAEs leading to treatment discontinuation was 6% in the vimseltinib arm. If approved, vimseltinib offers an effective systemic treatment to patients with TGCT and provides proven functional health and symptomatic benefit to a population living with substantial morbidity and limited treatment options. Abstract Number: TPS11587 Title: DCC-3116 in combination with ripretinib for patients with advanced gastrointestinal stromal tumor: A phase 1/2 study. Presenter: Sreenivasa Chandana, M.D., Ph.D., START Midwest, The Cancer & Hematology Centers Session Date: Saturday, June 1, 2024 Session Time: 1:30 – 4:30 PM CT Key Highlights: This is a phase 1/2, multicenter study designed to evaluate the safety, tolerability, and efficacy of DCC-3116 in combination with ripretinib. In Part 1, eligible patients will receive escalating oral doses of DCC-3116 combined with ripretinib 150 mg once daily (QD); the safety will be evaluated and the recommended phase 2 dose (RP2D) will be determined. In Part 2, eligible patients will receive the RP2D of DCC-3116 in combination with ripretinib 150 mg QD; antitumor activity will be evaluated. The trial is currently enrolling in the phase 1 dose escalation portion. About Deciphera Pharmaceuticals Deciphera is a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer. We are leveraging our proprietary switch-control kinase inhibitor platform and deep expertise in kinase biology to develop a broad portfolio of innovative medicines. In addition to advancing multiple product candidates from our platform in clinical studies, QINLOCK® is Deciphera’s switch-control inhibitor for the treatment of fourth-line GIST. QINLOCK is approved in Australia, Canada, China, the European Union, Hong Kong, Iceland, Israel, Liechtenstein, Macau, New Zealand, Norway, Singapore, Switzerland, Taiwan, The United Kingdom, and the United States. For more information, visit and follow us on LinkedIn and X (@Deciphera). Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, our expectations and timing regarding the potential for our preclinical and/or clinical stage pipeline assets to be first-in-class and/or best-in-class treatments, the timing of our NDA and MAA submissions for vimseltinib, and plans to present trial-in-progress poster for the ongoing Phase 1/2 study of DCC-3116 in combination with ripretinib at the 2024 ASCO Annual Meeting. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “seek,” “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: (i) risks associated with the timing of the closing of the proposed transaction, including the risks that a condition to closing would not be satisfied within the expected timeframe or at all or that the closing of the proposed transaction will not occur; (ii) uncertainties as to how many of Deciphera’s stockholders will tender their shares in the offer; (iii) the possibility that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the transaction; (iv) the possibility that competing offers will be made; (v) the outcome of any legal proceedings that may be instituted against the parties and others related to the merger agreement; (vi) unanticipated difficulties or expenditures relating to the proposed transaction, the response of business partners and competitors to the announcement of the proposed transaction, and/or potential difficulties in employee retention as a result of the announcement and pendency of the proposed transaction; (vii) Deciphera’s ability to successfully demonstrate the efficacy and safety of its drug or drug candidates, and the preclinical or clinical results for its product candidates, which may not support further development of such product candidates; (viii) comments, feedback and actions of regulatory agencies; (ix) Deciphera’s ability to commercialize QINLOCK® and execute on its marketing plans for any drugs or indications that may be approved in the future; (x) the inherent uncertainty in estimates of patient populations, competition from other products, Deciphera’s ability to obtain and maintain reimbursement for any approved product and the extent to which patient assistance programs are utilized; and (xi) other risks identified in our Securities and Exchange Commission (SEC) filings, including our Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, and subsequent filings with the SEC. 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. The Deciphera logo and the QINLOCK® word mark and logo are registered trademarks and the Deciphera word mark is a trademark of Deciphera Pharmaceuticals, LLC.

关注并星标CPHI制药在线4月29日，小野制药（ONO Pharmaceutical）宣布以25.6美元/股的价格收购Deciphera Pharmaceuticals，收购总价为24亿美元（173.5亿元），较上周五收盘溢价75%。预计交易将在7月至9月完成，届时Deciphera将成为小野制药全资子公司。这项交易将以全现金形式进行。受并购消息影响，Deciphera盘中大涨72.56%。图片来源：小野制药官网       对于小野制药来说，这笔交易提供了一种既可以发展癌症研究方向又能在其他市场获得更强有力立足点的方法。该公司首席执行官Gyo Sagara在一份声明中指出，收购Deciphera将强化小野制药在肿瘤学领域的布局，并加快其在美国和欧洲的业务发展活动。       去年以来，小野制药已经三次出手重金加码肿瘤治疗领域。包括：       1. 与计算生物学公司Turbine达成合作，Turbine将应用其端到端、可解释的细胞模拟技术Simulated Cell™ 平台，在计算中发现潜在治疗开发的新靶点，从而推动小野制药肿瘤产品线的扩展。       2. 与Macomics达成药物发现合作，以发现并开发用于癌症治疗的巨噬细胞靶向抗体疗法。根据协议条款，Macomics将利用ENIGMACTM巨噬细胞药物发现平台，针对新靶点识别、表征并开发候选抗体。小野制药将获得候选抗体的全球独家权利，以进行后续开发和商业化。       3. 与德国研究机构BioMed X展开了一项新的癌症免疫疗法联合研究项目，该研究项目的目标是通过利用嗜中性粒细胞的抗肿瘤效应设计下一代免疫疗法。       Deciphera管线中的潜力股们       Deciphera是一家位于马萨诸塞州沃尔瑟姆市的临床阶段生物制药公司，致力于通过解决耐药性的关键机制来改善癌症患者的生活。Deciphera利用其专有的激酶开关控制抑制剂平台来开发高度选择性，有效的小分子候选药物。Deciphera利用对激酶生物学的深刻理解以及专有的化学文库，有目的地设计将激酶维持在"关闭"或失活构象的化合物，这些候选药物可直接抑制与癌症的生长和扩散有关的激酶的活化。       Deciphera Pharmaceuticals首发管线Ripretinib已经在美国、欧洲、中国等40多个国家获批上市，用于四线治疗胃肠间质瘤（GIST）。Ripretinib在2023年实现1.6亿美元销售额，并正在向二线治疗拓展。Ripretinib是一种口服激酶开关抑制剂，目前还将其开发用于治疗晚期全身性肥大细胞增多症（ASM），神经胶质瘤和其他由KIT或PDGFRα激酶诱发的实体瘤等疾病。2019年6月，再鼎医药引进Ripretinib的大中华区权益，支付对价为2000万美元预付款+1.85亿美元里程碑金额，以及一定比例的销售分成。       Ripretinib之外，Deciphera还拥有CSF-1R抑制剂、ULK抑制剂、pan-RAF抑制剂、pan-KIT抑制剂、GCN2激活剂等多种研发管线，包括vimseltinib、DCC-3116（一种ULK抑制剂）以及多个其他的肿瘤学候选药物。Deciphera管线（图片来源：Deciphera Pharmaceuticals官网）       Vimseltinib是一款在研、强效、具高选择性的口服CSF1R激酶抑制剂，通过利用调节激酶构象激活的开关控制区的独特特征来选择性和有效地抑制CSF1R，用于治疗腱鞘巨细胞瘤（3期）、色素沉着的绒毛结节性滑膜炎（3期）和实体瘤（2期）等。       去年10月，Deciphera公布了vimseltinib在腱鞘巨细胞瘤 (TGCT) 患者中开展的关键3期MOTION研究的积极结果，使用vimseltinib治疗的ORR 出现了统计学上显着且具有临床意义的改善。在意向治疗 (ITT) 人群中，vimseltinib 组在第 25 周的 ORR 为 40%，安慰剂组为 0%（p<0.0001）。同时Deciphera还公布了一项国际、多中心、开放标签的1/2期研究的最新结果，该研究评估了vimseltinib对TGCT患者的安全性和有效性，结果显示：在安全性上，使用vimseltinib治疗耐受性良好，与先前披露的数据一致。没有胆汁淤积性肝毒性的证据。Deciphera预计在今年第二季度向美国FDA递交新药申请（NDA），并在今年第三季度向欧盟递交上市许可申请（MAA）。       目前全球仅第一三共pexidartinib这一款CSF-1R抑制剂获批了TGCT适应症，虽然带来了新的治疗方案，但pexidartinib具有严重的肝毒性并被列入黑框警告。因此，临床上仍然需要新一代安全性更高的CSF-1R抑制剂，vimseltinib则有望成为pexidartinib的me-better品种。       DCC-3116是Deciphera公司开发的一款选择性的小分子ULK1/2激酶抑制剂，旨在通过抑制负责启动自噬的ULK1/2激酶来抑制癌症自噬，从而影响肿瘤细胞的存活。DCC-3116是潜在的选择性ULK1/2抑制剂的FIC药物，也是目前该靶标唯一的临床药物。2022年ESMO会议上，公布了一项DCC-3116单药活性的临床数据。结果显示，DCC-3116单药在结直肠癌、胰腺癌等多种携带不同KRAS亚型突变的瘤种中具有初步的临床迹象，部分患者实现了疾病稳定。Deciphera公司希望在今年晚些时候能够确定用于2期临床试验的给药剂量。       小野制药肿瘤领域布局       小野制药（Ono Pharmaceutical）是日本一家专注于肿瘤学、免疫学、神经病学和专业研究领域的制药公司。       目前，小野制药已经上市的药物包括注射、口服和贴片三类。其中注射抗癌药物包括PD-1 Opdivo、治疗多发性骨髓瘤的Kyprolis（卡非佐米）、针对化疗后呕吐的Proemend（fosaprepitant）等。       PD-1基因是由日本京都大学本庶佑教授团队于1992年通过消减杂交技术首次发现，1996~2016年期间，小野制药与本庶佑教授共同申报了8项相关专利。期间，小野制药与美国制药公司Medarex联合开发PD-1抑制剂，而Medarex后期又被BMS收购；故随着纳武单抗在日本（2014年7月）、美国（2014年12月）、欧洲（2015年6月）、中国（2018年6月）的获批，市场销售分别由小野制药负责日本地区，BMS负责美国、欧洲和中国地区。据BMS 2023年财报，O药全球销售额为90亿美元，再加上小野制药在日本的10亿美元，总计超过100亿美元。       口服抗癌药物有BTK抑制剂Velexbru（tirabrutinib hydrochloride）、BRAF抑制剂Braftovi（encorafenib）和MEK抑制剂Mektovi（binimetinib）、针对化疗引起的恶心呕吐的Emend（阿瑞匹坦）以及癌症恶病质的Adlumiz（anamorelin）。小野制药肿瘤管线图片来源：只投BioTech       目前在小野制药的肿瘤管线中，既有着TIGIT、LAG-3、BTK、CD47这些热门肿瘤靶点，也有着ILT-4、EP4、MALT1这些新型靶点。整体研发策略一方面以O药为基础的免疫联合治疗在多癌种探索，另一方面在可成药新靶点持续挖掘潜力。       参考来源       1. 各公司官网       2. 智慧芽新药科讯【智药研习社近期线下课程预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~