ROR1 CAR-T (Oncternal Therapeutics)

小一年过去，Oncternal Therapeutics终于等到它的接盘侠，可以从容解散分家了。Oncternal是一家ROR1开发的失败者，经历了多次管线的挫折后，于2024年9月宣布停止临床试验并探索战略代替方案。2025年7月1日，Oncternal宣布，将其两个ROR1资产zilovertamab和ONCT-808出售给Ho'ola Therapeutics，打包价为300万美元预付款和潜在的高达6500万美元的里程碑付款。是接盘，还是捡漏？事实上，Oncternal出售的两款ROR1管线，都已经推进至临床开发阶段，是全球开发进度最快的ROR1靶向药物之二。无论是zilovertamab，还是ONCT-808，都有不足之处。不过，300万美元的首付款买到两款临床管线，甚至有一款一度推进了3期，属于是很低价了。基于两款管线的临床表现和临床进度，小编认为其价值很可能被低估了，尤其是zilovertamab。zilovertamabzilovertamab是一款ROR1单抗，被开发用于血液瘤和实体瘤治疗。同时，zilovertamab与BTK抑制剂ibrutinib（艾伯维）联用治疗套细胞淋巴瘤（MCL）的研究一度推进3期，使得zilovertamab成为全球首个进入3期临床的ROR1单抗。不过，早在2023年4月，Oncternal公司以BTK抑制剂快速变化的商业环境为由，结束了zilovertamab与ibrutinib的3期；同时取消了zilovertamab的优先级，以及关闭了其另一项1/2期试验。基于此前公布的临床数据来看，zilovertamab的疗效看起来还不错。在与ibrutinib联用的1/2期临床中，表达P53突变/del(17p)的CLL患者获得100%的无进展生存期（PFS），持续48个月。另外，默沙东（VelosBio）一款基于zilovertamab开发的ROR1 ADC药物zilovertamab vedotin也在临床中显示出具有竞争力的疗效数据——在两个剂量队里中实现了100%的完全缓解。危险的靶点，100%的CR此外，zilovertamab也未报告严重的安全性问题，同时基于zilovertamab以往所表现出的临床疗效来看，zilovertamab还是有开发潜力的。2个核心管线同时暴雷，首席医疗官出走（对于Oncternal此前莫名降低其优先级，转去开发ROR1 CAR-T和双效雄激素受体抑制剂，小编认为是该公司的决策失误，也是导致公司死亡的主要因素。）ONCT-808ONCT-808是一款自体的ROR1 CAR-T细胞治疗，是全球进度最快的ROR1 CAR-T项目之一。被开发用于治疗复发/难治性（R/R）侵袭性B细胞恶性肿瘤。2024年9月，ONCT-808的更新数据显示：在每个剂量中都表现出具有抗肿瘤活性，包括持续8个月的完全代谢反应和CAR-T细胞的长期持久性。但是CAR-T治疗预期会出现不良事件，以及在最高剂量队列中经历了因休克并发症导致的死亡事件。基于现有的临床表现和持续开发的资金要求，Oncternal公司终止了对ONCT-808的研究。ONCT-808的高毒性，是限制其开发的主要因素，其开发难度也会更高。神秘的买家买下zilovertamab和ONCT-808的Ho'ola Therapeutics，拥有了重新开发这两款ROR1管线的机会。这使得Ho'ola这家新成立于2025年3月的公司一跃成为临床阶段公司。此前未见有关Ho'ola的报道，也未知其利益相关者。小编进行“Ho'ola”检索，只查询到一家夏威夷独立医生集团Ho'ola health。值得注意的是，市场对于zilovertamab和ONCT-808态度较为冷淡，原研公司Oncternal都在今年3月从纳斯达克退市了。而它们的新拥有者很可能也不会获得来自投资者的关注，除非它们显示出新的希望。不过基于zilovertamab以往的表现，或许能写出新的故事。Oncternal解散根据新闻稿，该交易于2025年6月27日完成了。在资产出售之后，Oncternal的董事和其余员工已全部辞职，只剩下唯一成员Craig R. Jalbert担任Oncternal董事会的总裁、首席执行官、财务主管、秘书，以负责监督Oncternal业务的结束，包括剩余现金的任何未来分配和任何未来基于里程碑付款的权利。小结2020年末，ROR1因为几笔巨额交易成为市场的焦点。但是在这几年的开发当中，与ROR1药物疗效并肩的是其挥之不去的安全性问题，多款ROR1管线因为安全性问题停止开发。这也使得业内对于ROR1的评价降低，这是一个开发难度较高的靶点。参考资料：1.https://www.globenewswire.com/news-release/2025/07/01/3108259/0/en/Oncternal-Therapeutics-Announces-the-Sale-of-Select-Development-Programs-and-the-Wind-Down-of-its-Operations.html2.https://www.fiercebiotech.com/biotech/ror-deal-oncternal-sells-cancer-assets-mystery-biotech-3m-winds-down-operations3.https://www.oncternal.com/········

SAN DIEGO, July 01, 2025 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. today announced the sale of its zilovertamab and ONCT-808 programs to Ho’ola Therapeutics, Inc. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1), and ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets ROR1 using the binding domain from zilovertamab. Ho’ola will pay Oncternal a $3.0 million upfront payment, with $2.25 million paid immediately and $750,000 upon resolution of certain outstanding contractual obligations with third parties. Oncternal will also be eligible to receive up to $65.0 million in development, regulatory approval and sales milestone payments for the acquired products (including any future products derived from the acquired intellectual property). The development milestones consist of up to $5.0 million upon either the last patient enrolled in a pivotal clinical trial or a regulatory approval submission. The regulatory milestones consist of up to $40.0 million in connection with regulatory approvals. The sales milestone payment consists of $20.0 million upon achievement of a net sales threshold. The foregoing development and regulatory approval milestones are based on clinical trials and/or regulatory approvals in any of the following major markets: the U.S., United Kingdom, Germany, Spain, France or Italy, and Japan. The asset sale was completed on June 27, 2025, pursuant to an asset purchase agreement as of the same date. Oncternal also announced that, following the asset sale, Craig R. Jalbert has been appointed President, CEO, Treasurer, Secretary, and sole member of Oncternal’s board of directors, and Oncternal’s directors and remaining employees have resigned. Mr. Jalbert, a principal of the accounting firm Verdolino & Lowey, P.C., brings over 30 years of experience in overseeing the dissolution of companies. Mr. Jalbert will oversee the winddown of Oncternal’s operations, including any future distribution of remaining cash and future rights to any milestone-based payments. Oncternal cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negatives of these terms or other similar expressions. These statements are based on Oncternal’s current beliefs and expectations. Forward-looking statements include statements regarding the upfront and potential milestone consideration payable to Oncternal and plans related to, and timing of, the wind down the company. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Oncternal’s business, including, without limitation: we will be entirely dependent on Ho’ola Therapeutics for the development, regulatory approval and sales of any products subject to the asset purchase agreement; Ho’ola Therapeutics may not successfully develop any products from the asset purchase agreement due to the inherent risks in drug development as well as strategic decisions by Ho’ola Therapeutics on whether to continue any of the product programs; the timing, progress, mechanics and final results of Oncternal’s planned wind down may be delayed or cost more than expected which could delay or reduce the final payments to stockholders; and other risks described in Oncternal’s prior filings with the Securities and Exchange Commission. All forward-looking statements in this report are current only as of the date hereof and, except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Company Contact:Verdolino & Lowey, P.C.124 Washington Street, Suite 101Foxboro, MA. 02035Phone - 508-543-1720Oncternal@VLPC.com