MRT-2359

本期看点： 1. GSPT1靶向分子胶降解剂用于治疗转移性去势抵抗性前列腺癌（mCRPC）的早期临床试验结果积极，携带雄激素受体（AR）突变患者的靶病灶均观察到缩小，疾病控制率达100%。 2. PRO-XTEN双掩蔽CD3 T细胞衔接器（TCE）VIR-5500用于治疗mCRPC，在一项1期临床试验中使82%的可评估高剂量队列组患者实现前列腺特异性抗原（PSA）下降≥50%（PSA50）。 MRT-2359：公布1/2期联合治疗试验数据 Monte Rosa Therapeutics公司公布了一项进行中的1/2期临床研究的最新临床数据。MRT-2359是一款高效、高选择性、口服生物利用度良好的在研GSPT1靶向分子胶降解剂。包括前列腺癌在内的MYC驱动型肿瘤依赖增强的致癌蛋白翻译以支持快速生长。MRT-2359通过选择性降解翻译终止因子GSPT1以破坏蛋白翻译过程，从而产生治疗效果。MRT-2359治疗可降低多种与前列腺癌相关的致癌蛋白水平，包括AR、MYC及细胞周期蛋白D1-E2F，并在多种mCRPC临床前模型中显示出显著的抗肿瘤活性。 该研究评估其在研分子胶降解剂MRT-2359联合恩扎卢胺（enzalutamide），在既往接受多线治疗的mCRPC患者中的疗效。分析显示，整体15例可评估患者的RECIST疾病控制率达到67%（10/15），包含10例患者靶病灶出现缩小。携带AR突变患者的靶病灶均观察到缩小，疾病控制率达100%。数据显示治疗效果具有持续性，尤其是在AR突变患者或既往未接受AR抑制剂治疗的患者中更为明显。在AR突变患者中，5例中有2例治疗持续10个周期或更长，且截至数据截止日仍有2例继续接受治疗。安全性方面，MRT-2359联合恩扎卢胺总体耐受性良好，不良事件可控。公司计划于2026年第三季度启动一项新的验证性2期研究，针对携带AR突变的患者开展评估。 VIR-5500：公布1期临床试验数据 Vir Biotechnology公司公布了其在研药物VIR-5500用于治疗晚期mCRPC的1期临床试验数据。VIR-5500是一款靶向前列腺特异性膜抗原（PSMA）的PRO-XTEN双掩蔽CD3 T细胞衔接器，可在到达肿瘤微环境前保持非活性状态，从而降低脱靶效应并提升治疗指数。近日，安斯泰来（Astellas Pharma）与Vir Biotechnology达成超17亿美元的全球战略合作，将共同推进VIR-5500的开发与商业化。 此次公布的数据显示，IR-5500单药具有良好的安全性和耐受性，迄今未观察到剂量限制性毒性。截至2026年1月9日的数据，在≥3,000 µg/kg的高剂量队列中，82%（14/17）的可评估患者达到PSA50，53%（9/17）达到PSA下降≥90%（PSA90）；在RECIST可评估患者中，客观缓解率（ORR）达45%（5/11），其中4例已确认缓解。PSMA-PET影像也证实了多发肿瘤病灶（包括内脏转移灶）的显著缩小。 Pociredir：公布1b期临床试验的新数据 Fulcrum Therapeutics公司公布了其在研疗法pociredir在镰状细胞病（SCD）患者中开展的1b期PIONEER临床试验的新数据。Pociredir是一种靶向胚胎外胚层发育蛋白（EED）的口服小分子抑制剂。通过抑制EED，pociredir可有效下调关键的胎儿珠蛋白阻遏蛋白（包括BCL11A），从而导致胎儿血红蛋白（HbF）水平升高。 此次公布的数据显示，pociredir治疗表现出快速、显著且具有临床意义的疗效：12例患者在第12周时平均HbF的绝对水平从7.1%提升至19.3%（增加12.2个百分点），表达HbF的红细胞比例从31%升至63%，显示泛细胞型HbF诱导。58%（7/12）患者的HbF水平≥20%，所有患者的HbF水平均至少提升6.5个百分点。同时，溶血标志物改善、红细胞生成增强，并实现总血红蛋白平均升高超1 g/dL。截至2025年12月23日的数据，pociredir总体耐受性良好，未出现治疗相关严重不良事件（SAEs），亦无患者因治疗相关不良事件而停药。58%（7/12）的患者在治疗期间未发生任何血管阻塞危象（VOC）。 参考资料： [1] Vir Biotechnology Reports Positive Updated Phase 1 Results for PSMA-targeting, PRO-XTEN® Dual-masked T-Cell Engager VIR-5500 in Patients with Metastatic Prostate Cancer. Retrieved February 27, 2026, from https://investors.vir.bio/news/news-details/2026/Vir-Biotechnology-Reports-Positive-Updated-Phase-1-Results-for-PSMA-targeting-PRO-XTEN-Dual-masked-T-Cell-Engager-VIR-5500-in-Patients-with-Metastatic-Prostate-Cancer/default.aspx [2] Fulcrum Therapeutics Announces Positive 12-Week Results from the 20 mg Dose Cohort of the Phase 1b PIONEER Trial of Pociredir in Sickle Cell Disease. Retrieved February 27, 2026, from https://www.globenewswire.com/news-release/2026/02/24/3243339/0/en/Fulcrum-Therapeutics-Announces-Positive-12-Week-Results-from-the-20-mg-Dose-Cohort-of-the-Phase-1b-PIONEER-Trial-of-Pociredir-in-Sickle-Cell-Disease.html [3] SCYNEXIS Announces First Participants Dosed in a Phase 1 Single Ascending Dose and Multiple Ascending Dose Trial of Intravenous SCY-247. Retrieved February 27, 2026, from https://www.globenewswire.com/news-release/2026/02/26/3245564/0/en/SCYNEXIS-Announces-First-Participants-Dosed-in-a-Phase-1-Single-Ascending-Dose-and-Multiple-Ascending-Dose-Trial-of-Intravenous-SCY-247.html [4] TScan Therapeutics Completes Enrollment in Cohort C of Phase 1 ALLOHA™ Trial and Announces FDA Clearance of Investigational New Drug Applications for Heme Candidates TSC-102-A01 and TSC-102-A03. Retrieved February 27, 2026, from https://www.globenewswire.com/news-release/2026/02/26/3245412/0/en/TScan-Therapeutics-Completes-Enrollment-in-Cohort-C-of-Phase-1-ALLOHA-Trial-and-Announces-FDA-Clearance-of-Investigational-New-Drug-Applications-for-Heme-Candidates-TSC-102-A01-and.html [5] Zelluna Receives UK MHRA and Ethics Approval to Initiate ZIMA-101 First-in-Human Clinical Trial. Retrieved February 27, 2026, from https://www.globenewswire.com/news-release/2026/02/20/3241927/0/en/Zelluna-Receives-UK-MHRA-and-Ethics-Approval-to-Initiate-ZIMA-101-First-in-Human-Clinical-Trial.html [6] EuBiologics' shingles vaccine EuHZV matches active control in phase 1 interim data. Retrieved February 27, 2026, from https://www.koreabiomed.com/news/articleView.html?idxno=30721 [7] Opus Genetics Announces Initial Clinical Data from Phase 1/2 OPGx-BEST1 Gene Therapy Study at the Macula Society Annual Meeting. Retrieved February 27, 2026, from https://www.globenewswire.com/news-release/2026/02/27/3246599/0/en/Opus-Genetics-Announces-Initial-Clinical-Data-from-Phase-1-2-OPGx-BEST1-Gene-Therapy-Study-at-the-Macula-Society-Annual-Meeting.html [8] Mahzi Therapeutics Announces First Patient Dosed in Phase 1/2 UNITE Study of MZ-1866 for Pitt Hopkins Syndrome. Retrieved February 27, 2026, from https://www.prnewswire.com/news-releases/mahzi-therapeutics-announces-first-patient-dosed-in-phase-12-unite-study-of-mz-1866-for-pitt-hopkins-syndrome-302696349.html [9] Cartography Biosciences Doses First Patient in Phase 1 Trial of CBI-1214, a Highly Specific T-Cell Engager for the Treatment of Colorectal Cancer. Retrieved February 27, 2026, from https://www.businesswire.com/news/home/20260224232925/en/Cartography-Biosciences-Doses-First-Patient-in-Phase-1-Trial-of-CBI-1214-a-Highly-Specific-T-Cell-Engager-for-the-Treatment-of-Colorectal-Cancer [10] IDEAYA Biosciences Announces First-Patient-In for Phase 1 Trial of IDE034, a Potential First-In-Class B7H3/PTK7 Bispecific TOP1 ADC. Retrieved February 27, 2026, from https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-first-patient-in-for-phase-1-trial-of-ide034-a-potential-first-in-class-b7h3ptk7-bispecific-top1-adc-302696480.html [11] AC Immune Initiates Phase 1 Clinical Trial of NLRP3 Inhibitor. Retrieved February 27, 2026, from https://www.globenewswire.com/news-release/2026/02/24/3243363/0/en/AC-Immune-Initiates-Phase-1-Clinical-Trial-of-NLRP3-Inhibitor.html [12] Monte Rosa Therapeutics Presents Updated Clinical Data from Phase 1/2 Study of MRT-2359 in Combination with Enzalutamide in Heavily Pretreated Metastatic Castration-Resistant Prostate Cancer Patients at ASCO Genitourinary Cancers Symposium (ASCO GU). Retrieved February 27, 2026, from https://www.globenewswire.com/news-release/2026/02/24/3243353/0/en/Monte-Rosa-Therapeutics-Presents-Updated-Clinical-Data-from-Phase-1-2-Study-of-MRT-2359-in-Combination-with-Enzalutamide-in-Heavily-Pretreated-Metastatic-Castration-Resistant-Prost.html [13] Bloom Science Initiates Phase 1b Obesity Trial of BL-001, Advancing a Differentiated Approach Beyond GLP-1. Retrieved February 27, 2026, from https://www.prnewswire.com/news-releases/bloom-science-initiates-phase-1b-obesity-trial-of-bl-001-advancing-a-differentiated-approach-beyond-glp-1-302694371.html [14] QurAlis Demonstrates Effects on Disease Progression and Target Engagement in ANQUR Clinical Trial of QRL-201, a First-in-Class Precision Medicine in Development for Sporadic ALS. Retrieved February 27, 2026 from https://www.quralis.com/news/quralis-demonstrates-effects-on-disease-progression-and-target-engagement-in-anqur-clinical-trial-of-qrl-201-a-first-in-class-precision-medicine-in-development-for-sporadic-als/ [15] ADARx Pharmaceuticals Presents Onvuzosiran Data Supporting Potential for Sustained Attack-Free Rates with Reduced Treatment Burden in Patients with HAE. Retrieved February 27, 2026 from https://www.adarx.com/adarx-pharmaceuticals-presents-onvuzosiran-data-supporting-potential-for-sustained-attack-free-rates-with-reduced-treatment-burden-in-patients-with-hae/ 免责声明：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。 版权说明：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「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新