MAGEA4

近期，Immatics在ESMO 2024上展示了正在进行的针对 MAGEA4/8 的 TCR 双特异性分子TCER® IMA401 1期剂量递增试验的临床概念验证数据。 在公布临床数据的同时，Immatics也遗憾宣布，BMS已经选择了退货。双方的合作始于2021年，此前BMS支付的1.5亿美金首付款不再退回。 MAGEA4/8肽在头颈部鳞状细胞癌（HNSCC）、小细胞肺癌（SCLC）以及黑色素瘤、肉瘤亚型和其他实体瘤类型等几种实体瘤适应症中的发病率很高。 TCER® IMA401 是一种新型、下一代、半衰期延长的双特异性 T 细胞接合剂，结合了针对 HLA-A*02:01 呈递的 MAGEA4/8 肽的高亲和力 TCR 结构域、低亲和力 T 细胞募集抗体和用于延长半衰期的 Fc 部分，对各种实体癌具有高靶向拷贝数。与其他双特异性抗体或细胞疗法靶向的 MAGEA4 衍生肽相比，靶肽的密度高出 5 倍以上。 目前，IMA401 正在进行的1a/1b 期首次人体临床试验评估了其对复发/难治性实体瘤患者 (pts) 的效果。初步数据表明，该试验在大量接受过大量治疗的复发和/或难治性实体瘤患者中表现出初始抗肿瘤活性、持久的客观反应（包括持续 13 个月以上的确认反应）和可管理的耐受性。 截至 2024 年 7 月 23 日数据截止日，已有 35 名复发性和/或难治性实体瘤重度预处理患者接受了 IMA401 单药治疗，治疗剂量呈九级递增。接受治疗的患者包括16种不同实体瘤适应症的重度预处理患者。 在接受相关 IMA401 剂量和 MAGEA4/8 目标水平治疗的疗效人群中，客观缓解率 (ORR) 为 29%，确认的 ORR (cORR) 为 25%，疾病控制率 (DCR) 为 53%，肿瘤缩小率为 53% 。 药代动力学数据表明，IMA401中位终末半衰期超过两周（16.9 天），支持目前的每两周一次的给药方案以及未来延长至每四周一次的给药方案。 安全性方面，IMA401整体显示出可管理的耐受性，最常见的治疗相关不良事件包括淋巴细胞减少、细胞因子释放综合症（CRS）和中性粒细胞减少。 根据与百时美施贵宝的协议条款，所有IMA401开发和商业化权利将回归 Immatics，此前BMS支付的1.5亿美金首付款不再退回。随着临床试验的进展，Immatics计划下一步利用该产品候选物的潜力，重点招募具有高 MAGEA4/8 靶标表达的适应症，例如肺癌和头颈癌患者，寻求优化治疗方案，并探索通过将 IMA401 与检查点抑制剂相结合为患者提供的增量临床益处。 值得一提的是，这并非BMS自2024下半年以来的首次退货，而是接连终止的第3项2021年引入的项目。 今年7月，BMS基于内部产品组合的优先级调整，与卫材终止一款靶向FRα的ADC药物farletuzumab ecteribulin（MORAb-202）的全球战略合作。2021年6月，BMS与卫材就开发和销售MORAb-202达成总金额为31亿美元的合作协议。当时BMS向卫材支付了6.5亿美元的预付款，其中包括2亿美元的研发费用。合作终止后，卫材计划退还根据合作协议从BMS收到的2亿美元研发费用中未使用部分，并将其余部分记录为其他收入。 8月，BMS将TIGIT双特异性抗体项目的所有权归还给Agenus，该项目正处于针对实体瘤的早期试验阶段。这笔交易也是在2021年，当时以2亿美元的预付款达成的。吉利德和罗氏都有TIGIT项目，但罗氏于7月4日宣布II/III期SKYSCRAPER-06研究失败后取消了对该候选药物的临床试验 此前，即4月25日，BMS在其2024年第一季度的财报中表示，将实施一项全面的“战略生产力计划”，该计划包括组织管理结构重组，优化产品管线。 BMS计划在2025年底前，在全球范围内裁撤大约2200个工作岗位，占这家公司总员工的6.5%。其中，近900人将在6月开启的调整中离开。这场大裁员旨在到2025年底为公司节省约15亿美元，将该资金会直接投入到“前景看好”的管线项目。2200人！BMS又裁员了 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，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/商务/投稿 | 联系微信 wfj_GM 商务合作 稿件征集 点击了解详情 往期回顾 1 5月| 20家药企裁员（附名单） 2 18亿美元，ADC又出海! 宜联生物宣布新授权 3 2024 ASCO| 默沙东/科伦TROP2 ADC、信达、礼新CLDN18.2 ADC数据公布

BMS is ending its $150m deal with Immatics to help develop its bispecific. Image credit: Getty Images / sesame. Immatics has been left with the full rights to develop a bispecific molecule after its partner Bristol Myers Squibb (BMS) cut ties with the project. BMS has handed back both the development and commercialisation rights for IMA401 to the biopharmaceutical company after a $150m upfront payment in 2021, with an expected $770m in milestone payments. Immatics said the collaboration ended due to an ongoing portfolio prioritisation push by BMS. The announcement comes as Immatics announces Phase I, proof-of-concept data for its T cell receptor (TCR) bispecific, TCER IMA401, at the European Society of Medical Oncology meeting, taking place in Barcelona, Spain, from 13 to 17 September. The Phase Ia dose escalation study (NCT05359445) has enrolled 35 patients with solid tumours across 16 indications who are HLA-A*02:01 and MAGEA4/8-positive and had received a median of four and up to eight lines of prior systemic treatments. See Also: Bicara Therapeutics closes $362m IPO in flurry of biotech listing activity MaxCyte and Kamau Therapeutics sign platform license agreement As of a 23 July 2024 data cutoff, there was an objective response rate (ORR) of 29%, confirmed ORR (cORR) of 25%, disease control rate (DCR) of 53% and tumour shrinkage rate of 53%. Immatics’s chief development officer Dr Carsten Reinhardt said: “We are very pleased to observe initial anti-tumour activity, including durable objective responses, during dose escalation in a heavily pre-treated patient population and across several solid tumour types. “As the clinical trial progresses, our goal will be to further leverage the potential of this product candidate by focusing on the enrolment of indications with high MAGEA4/8 target expression, such as lung and head and neck cancer patients, seeking to optimise the treatment schedule and also exploring the incremental clinical benefit available to patients through combining IMA401 with a checkpoint inhibitor.” IMA401 is a bispecific fusion protein that acts by targeting cells expressing MAGEA4 and MAGEA8, both of which are expressed at higher levels in tumour conditions. Current data supports a two-week dosing schedule but Immatics is hopeful to reduce this to once every four weeks. Immatics also says that IMA401 has a manageable tolerability profile. More data is expected in 2025. Immatics has several other drugs in the pipeline, including IMA402 and IMA203 . Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

HOUSTON, TX, USA and TUEBINGEN, Germany I September 16, 2024 I Immatics N.V. (NASDAQ: IMTX, “Immatics” or the “Company”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today presented the proof-of-concept clinical data for the first candidate of its next-generation, half-life extended TCR Bispecifics platform, TCER® IMA401 (MAGEA4/8), during an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2024. Initial data from the IMA401 Phase 1a first-in-human dose escalation basket trial in a broad range of heavily pretreated patients with recurrent and/or refractory solid tumors showed initial anti-tumor activity, durable objective responses, including confirmed responses ongoing at 13+ months, and a manageable tolerability profile. The data from the ongoing Phase 1 trial will be presented today by Martin Wermke, M.D. during the Investigational Immunotherapy oral presentation session at the ESMO Congress 2024. The IMA401 data slides are accessible in the ‘ Events & Presentations ’ section of the Investor & Media section of the Company’s website. “Today marks the achievement of a major milestone for Immatics as the data presented confirm clinical proof-of-concept for our proprietary TCER® therapeutic approach and IMA401, our next-generation, half-life extended TCR-based bispecific targeting a novel tumor-specific peptide derived from MAGEA4/8. We are very pleased to observe initial anti-tumor activity, including durable objective responses, during dose escalation in a heavily pre-treated patient population and across several solid tumor types,” said Carsten Reinhardt, M.D., Ph.D., Chief Development Officer at Immatics. “As the clinical trial progresses, our goal will be to further leverage the potential of this product candidate by focusing on the enrollment of indications with high MAGEA4/8 target expression, such as lung and head and neck cancer patients, seeking to optimize the treatment schedule and also exploring the incremental clinical benefit available to patients through combining IMA401 with a checkpoint inhibitor.” In addition, the collaboration with Bristol Myers Squibb (NYSE: BMY) for the co-development of IMA401 has ended due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. The existing collaboration and license agreement signed in December 2021 will terminate effective December 12, 2024. Thereafter, all IMA401 development and commercialization rights will be reverted to Immatics. Immatics is not obligated to refund Bristol Myers Squibb any part of the $150 million upfront received under the collaboration and is not required to make any future milestone payments to Bristol Myers Squibb; the parties will engage in a wind-down period as stipulated under the collaboration agreement. Based on the terms of the agreement with Bristol Myers Squibb, Immatics has been responsible for conducting the ongoing Phase 1 clinical trial. Immatics intends to advance IMA401 further through clinical development. The next data update is expected in 2025. “Building on the initial anti-tumor activity observed in heavily pretreated patients with solid tumors, we are delighted to bring this highly promising drug candidate back into our pipeline as a wholly owned asset,” said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. “We see tremendous potential in going after cancers that express MAGEA4 and MAGEA8, complementing our PRAME franchise and strengthening our ability to deliver a meaningful impact on the lives of solid cancer patients.” Key Clinical Findings from TCER® IMA401 Monotherapy Phase 1 Trial Patient baseline characteristics: Heavily pretreated patients with a broad range of tumor types As of data cut-off on July 23, 2024, 35 heavily pretreated patients with recurrent and/or refractory solid tumors have been treated with IMA401 monotherapy across nine escalating dose levels. The treated patient population is composed of patients with 16 different solid tumor indications who are both HLA-A*02:01 and MAGEA4/8-positive, had received a median of four and up to eight lines of prior systemic treatments and the majority have an ECOG performance status of ≥ 1. The safety population includes all 35 patients treated with IMA401. 29 patients were evaluable for efficacy analysis, of which 17 patients were treated at relevant dose and target levels 1 . Safety: Treatment with IMA401 demonstrates a manageable tolerability profile IMA401 demonstrated an overall manageable tolerability profile in the 35 patients treated. The most frequent treatment-related adverse events (AEs) were transient lymphopenia and mild to moderate cytokine release syndrome (CRS) with the majority of CRS occurring at the first dose. Both AEs are consistent with the proposed mechanism of action and reported for other bispecific T cell engagers. Neutropenia was also observed at high dose levels and occurred mostly at the initial target dose in patients with and without dexamethasone pre-medication. High-grade neutropenia was fully resolved in all cases except one. Dose escalation for the trial is ongoing and the maximum tolerated dose has not yet been determined. Pharmacokinetics: Next-generation TCER® format shows extended half-life in solid cancer patients IMA401 demonstrated an “antibody-like” median half-life of over two weeks (16.9 days). This supported the switch to q2w dosing (once every two weeks) during dose escalation. In addition, the data support pursuing increased dosing intervals of up to q4w (once every four weeks), which could further offer an ideal dosing interval for potential combination with checkpoint inhibitors. Initial anti-tumor activity: IMA401 demonstrates initial anti-tumor activity in multiple tumor types As of data cut-off on July 23, 2024, three of four confirmed responses were ongoing at 13+, 8+ and 3+ months. Deep responses (tumor shrinkage of ≥50%) were observed in four patients (head and neck squamous cell carcinoma, neuroendocrine tumor of unknown primary, cutaneous and mucosal melanoma). The data obtained also indicate that objective responses are associated with MAGEA4/8 target expression level. 1 Patients in this analysis had received IMA401 infusions ≥ 1 mg and showed MAGEA4/8 target expression higher than the MAGEA4/8 high qPCR threshold (n=17). About IMA401 TCER® IMA401 is Immatics’ most advanced TCER® molecule from the Bispecifics pipeline that targets an HLA-A*02-presented (human leukocyte antigen) peptide derived from two different cancer-associated proteins, melanoma-associated antigen 4 and/or 8 (“MAGEA4/8”). The MAGEA4/8 peptide has been identified and validated by Immatics’ proprietary mass spectrometry-based target discovery platform XPRESIDENT® and is presented at a 5-fold higher copy number per tumor cell than the MAGEA4 peptide targeted in other clinical trials. TCER® IMA401 is currently being evaluated in a Phase 1 basket trial in patients with solid tumors expressing MAGEA4/8. The MAGEA4/8 peptide has a high prevalence in several solid tumor indications such as head and neck squamous cell carcinoma (HNSCC), small cell lung cancer (SCLC), as well as melanoma, sarcoma subtypes and other solid cancer types. – END – About Immatics Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer. Immatics intends to use its website www.immatics.com as a means of disclosing material non-public information. For regular updates you can also follow us on X , Instagram and LinkedIn . SOURCE: Immatics