WU-NK-101

当地时间8月27日，开创下一代同种异体体外CAR-T细胞疗法的临床生物技术公司Wugen宣布完成由Fidelity领投的1.15亿美元融资，融资将推进正在进行的WU-CART-007在复发/难治性T细胞急性淋巴细胞白血病（T-ALL）和T细胞淋巴母细胞淋巴瘤（T-LBL）中的关键T-RRex研究。推进与美国FDA和欧洲药品管理局（EMA）的监管合作，以及商业规模生产的准备。 WU-CART-007是一种靶向CD7、CRISPR编辑的同种异体CAR-T细胞疗法，有可能成为第一种获批的用于T细胞恶性肿瘤的“通用型”CAR-T，并计划于2027年向美国食品药品监督管理局（FDA）提交上市申请。在一项已完成的全球1/2期研究中，WU-CART-007在推荐的2期剂量下实现了91%的总体缓解率（ORR）和73%的复合完全缓解率（CRc）。中位反应持续时间超过六个月，安全性可控。这些数据在2024年美国血液学会（ASH）年会上公布，大大超过了当前标准疗法所取得的成果。 值得关注的是，Wugen的研发重心近年来发生了显著变化。2021年，该公司以自然杀伤细胞（NK细胞）疗法WU-NK-101为核心，完成1.72亿美元融资，并于2023年启动该候选产品的首次人体白血病临床试验，早期数据显示其有望成为“同类最佳”的NK细胞疗法。然而，随着WU-CART-007在临床前和早期临床阶段表现出色，这款CAR-T疗法迅速取代WU-NK-101成为公司的核心资产。2023年底，Wugen公布WU-CART-007的1/2期临床数据；2024年中，更新2期临床结果，并于当年年底确定启动关键3期试验。截至目前，Wugen已从研发管线中移除WU-NK-101及另一款NK细胞疗法，将资源集中用于拓展WU-CART-007的适应症范围。 Wugen总裁兼首席执行官Kumar Srinivasan博士表示：“此次融资对Wugen来说是一个决定性的时刻，因为我们正在通过我们正在进行的关键研究推进WU-CART-007，并为2027年提交BLA指明了明确的道路。复发和难治性T-ALL/T-LBL是对当前治疗方案具有抵抗力的侵袭性恶性肿瘤。我们致力于提供一种可获得的现成疗法，可以显著改善患者的护理轨迹。我们感谢世界级投资者联盟的支持，他们与我们分享了改变T细胞恶性肿瘤治疗格局的愿景。” 此次1.15亿美元融资的顺利完成，不仅体现了投资机构对Wugen研发实力和WU-CART-007临床潜力的高度认可，也为该疗法的后续研发提供了坚实的资金保障。在全球细胞与基因治疗领域蓬勃发展的背景下，Wugen的这一突破有望推动T细胞癌症治疗迈向新的阶段，同时也为异体CAR-T疗法的研发与商业化提供了宝贵的借鉴经验。

Wugen is running a pivotal trial to support a FDA approval filing for potentially the first off-the-shelf CAR-T for T-cell malignancies in 2027.\n Wugen has raised $115 million, tapping a Fidelity-led syndicate to fund its pursuit of FDA approval for the first off-the-shelf CAR-T for T-cell malignancies. A pivotal trial is underway, putting the company on track to seek approval in 2027.The funding will support T-RRex, an ongoing pivotal trial of WU-CART-007 in relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LBL). Wugen makes the therapy by engineering donor T cells to target CD7, an antigen expressed in most newly diagnosed T-ALL and T-LBL patients. The biotech reported a 91% response rate in a phase 1/2 trial. While CAR-T cells have enjoyed successes in B-cell malignancies, efforts to apply the modality to T-cell cancers have run into complications. Making CAR-T cell therapies from a patient’s T cells creates the risk that the drug product will be contaminated with malignant cells. To further complicate matters, CAR-T cells engineered to recognize T-cell antigens can turn on themselves, a problem known as “fratricide.”WU-CART-007 is designed to overcome the barriers to the treatment of T-cell cancers. Using donor cells eliminates the risk of contamination with malignant cells. To prevent fratricide, Wugen used CRISPR-Cas9 to delete CD7, meaning the CAR-T cells lack the receptor that they target. St. Louis-based Wugen was focused on the natural killer cell program WU-NK-101 when it raised $172 million in 2021. The biotech started a first-in-human leukemia trial of the candidate in 2023, leading to phase 1 data that researchers said suggested WU-NK-101 could be a best-in-class NK cell therapy.Yet, WU-CART-007 rose quickly to replace the NK cell therapy as Wugen’s lead asset. The biotech posted phase 1/2 data late in 2023 and reported phase 2 data around the middle of 2024. Before the year drew to a close, Wugen committed to running a pivotal trial. The company said it had dosed the first patients in the pivotal trial in March. The biotech completed the shift in focus by scrubbing WU-NK-101 from its pipeline. In June, Wugen was still listing WU-NK-101 and another NK cell therapy alongside WU-CART-007 in its pipeline. Today, the NK cell therapies are gone, replaced by an expanded set of indications for WU-CART-007.Wugen has identified T-cell non-Hodgkin lymphoma, acute myeloid leukemia and autoimmune disorders as other opportunities for WU-CART-007 but is yet to enter the clinic in those settings. The top priority is to deliver data on the cell therapy in T-ALL and T-LBL to support filings for approval in 2027.