Boserolimab

1. 默沙东HIF-2α抑制剂获欧盟批准两项适应症 2月18日，默沙东（MSD）宣布，欧盟委员会已有条件批准其口服低氧诱导因子2α（HIF-2α）抑制剂Welireg（belzutifan）上市，作为单药治疗下列适应症：1）von Hippel-Lindau（VHL）病成人患者，他们携带不适合手术、需要治疗的局部肾细胞癌（RCC）、中枢神经系统（CNS）血管母细胞瘤或胰腺神经内分泌肿瘤（pNET）；2）接受过两线或以上治疗方案（其中包含PD-1或PD-L1抑制剂及至少两种血管内皮生长因子靶向治疗）后疾病进展的成人晚期透明细胞RCC患者。新闻稿指出，Welireg是欧盟批准的首个HIF-2α抑制剂，也是治疗VHL病相关肿瘤的首个全身性治疗药物。这两个适应症的批准分别基于LITESPARK-004和LITESPARK-005试验的结果。在VHL病相关RCC患者（n=61）中，Welireg的客观缓解率（ORR）为49%（95% CI，36–62)；在RCC患者中，Welireg与活性对照相比，降低透明细胞RCC患者疾病进展或死亡风险25%（HR=0.75，95% CI，0.63–0.90；p=0.0008），ORR为22%vs4%。 2. 潜在“first-in-class”抗癌小分子获FDA优先审评资格 2月18日，Chimerix公司宣布，美国FDA已受理该公司为在研疗法dordaviprone递交的新药申请（NDA），用于治疗复发性H3 K27M突变弥漫性胶质瘤患者。FDA同时授予该申请优先审评资格，预计在2025年8月18日之前完成审评。Dordaviprone是一款潜在“first-in-class”小分子药物，能够选择性靶向线粒体蛋白酶ClpP和多巴胺受体D2。新闻稿指出，dordaviprone有望成为首款针对这一患者群体的获批疗法。Dordaviprone的新药申请得到2期临床试验主要分析结果的支持，此前发布的数据显示，在使用RANO 2.0（一种神经肿瘤学缓解评估标准）进行评估时，dordaviprone在H3 K27M突变弥漫性胶质瘤患者中达到28%的客观缓解率，中位缓解持续时间为10.4个月。 3. 默沙东启动三阴乳腺癌CD27+PD-1联合治疗临床 2月17日，默沙东在clinical trials网站上，登记了CD27抗体Boserolimab (MK-5890)联合PD-1抗体Pembrolizumab以及化疗在早期三阴乳腺癌患者中的2期联合治疗临床试验(NCT06829199)，该临床预计于2025年3月启动，入组人数为100例。2024年AACR会议期间，默沙东首次公布了Boserolimab (MK-5890)+Pembrolizumab联合疗法在三阴乳腺癌中的一期人体试验数据。数据显示在41位可评估患者中，客观响应率达到了51%，疾病控制率到了80%，中位PFS达到了11.1个月。 4. 只需一次用药！PCSK9体内基因编辑新药IIT研究数据公布 2月18日，锐正基因宣布，该公司和蚌埠医学院第一附属医院发起的“ART002注射液治疗杂合子家族性高胆固醇血症的多中心、开放、单臂、探索性临床研究”（IIT）的数据显示：只需一次用药，锐正基因自主开发的体内基因编辑产品ART002即可达到药效饱和，并安全有效地降低低密度脂蛋白胆固醇（LDL-C）。这标志着体内基因编辑治疗高胆固醇血症迈出了关键一步。ART002是一款以LNP为载体的体内基因编辑新药，旨在通过单次用药，精准编辑LDL-C调控基因PCSK9，以达到持久降低LDL-C水平、降低心血管疾病发病风险的目标。 5. 诺诚健华BCL-2抑制剂获批开展注册性III期临床试验 2月17日，诺诚健华宣布其自主研发的BCL-2抑制剂ICP-248（Mesutoclax）联合BTK抑制剂奥布替尼一线治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）获国家药品监督管理局（NMPA）药品审评中心（CDE）批准开展注册性III期临床试验。诺诚健华表示，目前已启动该临床研究。 6. 拜耳帕金森病基因疗法获FDA再生医学先进疗法认定 2月19日，拜耳全资拥有并独立运营的基因治疗子公司AskBio宣布：其用于治疗帕金森病（PD）的基因治疗药物AB-1005已获得美国FDA授予的再生医学先进疗法（RMAT）认定。AB-1005是一种基于2型腺相关病毒（AAV2）的基因治疗药物，其中包含人胶质细胞源性神经营养因子（GDNF）转基因，可通过神经外科直接注射（MRI监测的对流增强给药方式）在大脑局部区域实现GDNF的稳定和持续表达。FDA认定AB-1005符合RMAT标准这一决定是在对AskBio提供的信息和数据进行审查后做出的，包括AB-1005的1b期开放标签、非对照研究的临床证据。AskBio的1b期临床研究36个月的数据显示，AB-1005的给药耐受性良好，未出现与产品相关的严重不良事件。此外，中度PD患者在多个与该疾病相关的临床量表上显示出改善或稳定的趋势，轻度PD患者组的大多数受试者整体临床状况保持稳定。 1. 12.4亿美元：石药集团ROR1 ADC授权给Radiance Biopharma 2月19日，石药集团发布公告，将ROR1 ADC新药SYS6005的美国、欧盟、英国、瑞士、挪威、冰岛、列支敦士登、阿尔巴尼亚、黑山、北马其顿、塞尔维亚、澳大利亚和加拿大的开发和商业化权益授权给Radiance Biopharma。根据协议，Radiance Biopharma支付1500万美元预付款，1.5亿美元开发和监管里程碑金额，10.75亿美元销售里程碑金额，以及一定比例的销售分成。协议总金额高达12.4亿美元。SYS6005已经获批临床。 内容来源于网络，如有侵权，请联系删除。

– ADU-1805 is a potential best-in-class monoclonal antibody targeting SIRPα to block the SIRPα-CD47 checkpoint – – Phase 1 study of ADU-1805 as a single agent and in a combination regimen in advanced solid tumors expected to begin second quarter of this year – Exelixis, Inc. (Nasdaq: EXEL) and Sairopa B.V. (Sairopa) today announced that the U.S. Food and Drug Administration (FDA) has cleared Sairopa’s Investigational New Drug (IND) Application to evaluate the safety and pharmacokinetics of ADU-1805 in adults with advanced solid tumors. As a monoclonal antibody active against all human alleles of SIRPα, ADU-1805 has the potential to address a broader patient population than other SIRPα-directed therapies. “The clearance of this Investigational New Drug Application for ADU-1805 is an exciting milestone for our expanding biologics pipeline, marking the first of many anticipated advancements we expect this year,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “Based on its best-in-class potential and broad applicability, we look forward to learning more about ADU-1805 from the upcoming phase 1 trial across multiple tumor types, as we continue toward our goal of finding innovative solutions for patients with advanced cancers.” By blocking SIRPα, a significant immune-suppressive component of the tumor microenvironment, ADU-1805 has the potential to improve the immune system’s ability to attack tumors. ADU-1805 has been optimized to bind preferentially to SIRPα compared with other SIRP family members, which may enhance its ability to stimulate immune cells. Under the terms of the clinical development and option agreement announced in November 2022, Exelixis has the option to obtain an exclusive, worldwide license to develop and commercialize ADU-1805 and other anti-SIRPα antibodies upon review of data from prespecified phase 1 clinical studies of ADU-1805 to be completed by Sairopa during the option period. This IND clearance triggers a $35 million milestone payment to Sairopa which will be paid in the first quarter of 2023. “Given the robust preclinical data generated, we are thrilled that ADU-1805 is now able to advance to the clinic,” said Laura Lassouw-Polman, Chief Operating Officer, Sairopa. “This is an important step forward in our partnership with Exelixis to explore the potential of ADU-1805, advancing our mission to develop therapies that modulate immune system activity to improve outcomes for cancer patients.” About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by bi-coastal centers of discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on Twitter, like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn. About Sairopa Sairopa B.V. is a clinical-stage company that develops novel treatments for cancer by modulating the patient’s immune system. In April 2021 Sairopa acquired, backed by Van Herk Investments, a portfolio of therapeutic antibodies from Chinook Therapeutics, Inc. These antibodies were originally developed by BioNovion/Aduro Biotech Europe using the proprietary B-Select antibody platform that was also used to identify pembrolizumab (Keytruda™), BION-1301 and MK-5890 (Guelen et al., 2022). For more information about Sairopa, please visit www.sairopa.com. SOURCE: Exelixis 内容来源于网络，如有侵权，请联系删除。