Bemcentinib

Oslo-based Oncoinvent\'s lead radiopharma is in phase 2 trials.\n BerGenBio, reeling from the failure of its lead cancer drug, has opted to merge with fellow Norwegian cancer biotech Oncoinvent.The deal will see Oncoinvent’s shareholders own 75% of the merged company, with BerGenBio’s shareholders owning the remaining 25%. The resulting entity, which will operate under the Oncoinvent brand, will be focused on Oncoinvent’s lead radiopharma asset Radspherin.BerGenBio, which is based in Bergen, Norway, put its decision to go ahead with the merger in the context of the discontinuation in February of the biotech’s AXL kinase inhibitor bemcentinib. The company blamed a lack of responses in a phase 2 study of the lead candidate in non-small cell lung cancer and said at the time that it would now consider its strategic options—including a potential merger or sale.“This merger, which is backed by the boards of both companies, is the result of an extensive review that explored a range of strategic options for BerGenBio,” Anders Tullgren, chair of BerGenBio’s board, said in a June 30 postmarket release.“The merger gives BerGenBio shareholders a part of an exciting company leveraging Norwegian radiopharmaceutical technology, which has already seen encouraging preliminary efficacy data, without safety concerns,” Tullgren added. “We are confident that this is the best option for current BerGenBio shareholders.”The merger values BerGenBio at 65 million Norwegian kroner ($6.5 million) and Oncoinvent at 195.5 million kroner ($19.4 million).The deal will provide an additional 45 million kroner ($4.5 million) to fund Oncoinvent\'s clinical development plan, which is headed up by Radspherin, an alpha-emitting radionuclide radium-224 being tested in peritoneal cancer in patients who have had surgery for colorectal or ovarian cancers.Radspherin is currently being evaluated in a phase 2 trial across the U.S., UK and Europe with a readout penciled in for the second half of 2026. So far, preliminary efficacy data have been “highly encouraging,” Oncoinvent said in the release.The plan once the merger is completed is for a fully underwritten rights issue of 130 million kroner ($12.9 million), which should pave a cash runway past that readout and into 2027.“We are very excited for the time ahead and to continue the execution of our focused strategy to develop Radspherin in ovarian cancer,” Oncoinvent CEO Øystein Soug said in the release.“We are on track with our randomised phase 2 trial,” Soug added. “Going forward with a strengthened balance sheet, we believe the company will be a transformative force in the radiopharmaceutical therapy field, improving the lives of patients with cancer in the peritoneal cavity.”Oslo-based Oncoinvent was founded by Øyvind Bruland, M.D., Ph.D., and Roy Larsen, Ph.D., the pioneers behind Xofigo, a prostate cancer radiopharma drug that was acquired by Bayer in 2014 as part of its acquisition of Algeta. 

帕金森病（Parkinson’s Disease，PD），是一种影响运动和认知功能的神经退行性疾病，也是世界上第二常见的神经退行性疾病，仅次于阿尔茨海默病（AD），影响着约 1%-2%的65岁及以上老人。随着全球人口老龄化，帕金森病患病率还将大幅增加。病理性α-突触核蛋白（α-Syn）在不同脑区聚集介导了帕金森病的疾病进展。聚集的α-Syn蛋白形成纤维，以朊病毒样（Prion-like）方式发挥作用，在大脑的不同区域传播α-Syn病理，然而，其在神经元之间传递的分子机制，目前仍不清楚。之前的研究显示，α-Syn通过不同受体的内吞作用被内化，然而，其在神经元上的特异性受体仍有待完全鉴定。郁金泰团队曾于2020年10月在Science Advances期刊发表论文，首次发现了FAM171A2基因的单核苷酸多态性（rs708384）与帕金森病等神经退行性疾病的风险增加有关。帕金森病患者的脑脊液（CSF）中FAM171A2蛋白水平增加，并且与脑内α-Syn高聚集的指征相关。2025年2月20日，复旦大学附属华山医院郁金泰教授团队联合复旦大学脑科学转化研究院袁鹏教授及中国科学院上海有机化学研究所刘聪教授（博士后吴凯敏为第一作者），在国际顶尖学术期刊Science上发表了题为：Neuronal FAM171A2 mediates α-synuclein fibril uptake and drives Parkinson’s disease的研究论文。该研究首次发现了帕金森病（PD）的全新治疗靶点——FAM171A2，并利用基于人工智能的蛋白质结构预测和虚拟筛选技术，成功找到了具有潜在治疗作用的小分子化合物。这项研究发现的全新治疗靶点和前在治疗药物有望从疾病早期对帕金森病进行干预，延缓疾病进展，结合现有的对症治疗手段，有望实现帕金森病病因治疗与症状缓解的双重突破。在这项最新研究中，研究团队通过对超过100万样本的大规模全基因组关联分析（GWAS），发现FAM171A2基因的5个突变（例如rs850738、rs708384）与帕金森病风险显著相关。帕金森病患者的脑脊液（CSF）中FAM171A2蛋白水平升高，且与α-Syn病理标志物呈负相关，提示其参与了α-Syn的异常聚集。进一步实验验证显示，过表达FAM171A2会促进α-Syn纤维的被神经元内吞，加剧病理扩散（例如向黑质、纹状体的扩散）和运动功能障碍。而敲低FAM171A2能够减少α-Syn纤维的内吞，保护多巴胺能神经元，从而改善小鼠的运动表现。研究团队在小鼠神经元中特异性敲除FAM171A2，进一步验证了神经元来源的FAM171A2在α-Syn病理传播中是必要的。从机制上来说，FAM171A2蛋白的胞外结构域1通过静电力与α-Syn的C端相互作用，且高度选择性地结合病理性α-Syn（纤维形式），其对纤维形式α-Syn的选择性结合是单体形式α-Syn的超1000倍。也就是说，位于神经元上的FAM171A2蛋白能够高度选择性的结合病理性α-Syn，使其通过内吞作用进入神经元内，诱导神经元内的正常的单体形式的α-Syn发生错误折叠，转变为病理性α-Syn，进而诱导神经元死亡以及在神经元之间传播。接下来，研究团队使用AlphaFold-Multitimer预测了FAM171A2-α-Syn复合物结构，并利用虚拟筛选技术，从7173种化合物中筛选出了一种小分子药物——Bemcentinib，其能够竞争性结合α-Syn的C端，从而阻断FAM171A2与病理性α-Syn结合，抑制FAM171A2介导的神经元对病理性α-Syn的内吞。总的来说，该研究首次阐明了FAM171A2作为病理性α-Syn的神经元受体，揭示了其驱动帕金森病病理传播的分子机制，并成功筛选到了潜在抑制剂，为帕金森病的精准治疗提供了新方向。未来研究可聚焦于靶向FAM171A2的药物开发及多维度验证其临床价值。相关阅读：2024年11月22日，复旦大学附属华山医院郁金泰、毛颖团队与复旦大学类脑智能科学与技术研究院程炜、冯建峰团队合作，在国际顶尖学术期刊Cell在线发表了题为：Atlas of the plasma proteome in health and disease in 53,026 adults的研究论文。这项研究全面绘制了人类健康与疾病蛋白质组图谱，并结合人工智能大数据分析方法，构建了疾病诊断预测模型以及发现了26个药物治疗新靶点，为精准医学的实施提供了重要科学依据。该研究于2025年1月9日，登上了Cell期刊封面，该封面描绘了一个由蛋白质构成的人类，正在借助人工智能（由芯片和二进制代码代表）的帮助来检查自己的健康状况（通过心电图监测界面来体现）。参考资料：1.https://www.science.org/doi/10.1126/sciadv.abb30632.https://www.science.org/doi/10.1126/science.adp36453.https://www.cell.com/cell/fulltext/S0092-8674(24)01268-6--------- End ---------感兴趣的读者，可以添加小邦微信加入读者实名讨论微信群。添加时请主动注明姓名-企业-职位/岗位或姓名-学校-职务/研究方向。