Sirolimus Albumin-Bound

近日，精准肿瘤公司Aadi Bioscience宣布将裁撤其研发人员的80%，Aadi本身也会聘请一家外部咨询公司寻求股东价值最大化。根据该公司公告，管线调整和R&D员工的人力资源减少将至少将其现金跑道延长至2026年下半年。 导致该公司做出这一决定的是该公司核心管线白蛋白结合型西罗莫司的II期临床数据。独立数据监测委员会的分析表明，该研究不太可能到达支持加速批准所需的疗效阈值。这使得该公司将暂停PRECISION1注册意向试验。 其实解雇的预兆在此前8月16日发布的SEC文件中就可以看到，当时该公司宣称将将解雇22名员工，占其员工总数的32%，而该公司共有48名研发人员，考虑到80%的裁撤，届时该公司可能不剩下多少研发人员了，被收购可能是这家公司未来的结局。 有趣的是，目前岌岌可危的Aadi本身也是收购其他公司的产物。在2021年时，已经走向破产道路的眼科治疗公司Aerpio Pharmaceuticals通过拍卖资产与Aadi Bioscience合并，合并后的Aadi Bioscience全力开始推动白蛋白结合型西罗莫司，尽管如此，这一举措仍未能拯救白蛋白结合型西罗莫司的颓势。 白蛋白结合型西罗莫司的失利 白蛋白结合型西罗莫司可以说是Aadi Bioscience公司的核心。机制机理来自于mTOR信号通路抑制。而白蛋白结合型药物能够利用白蛋白的自然属性，通过血液循环系统流经肿瘤组织血管时，通过EPR效应（增强渗透滞留效应）富集于肿瘤组织间液，实现药物的靶向递送，因此就能实现mTOR抑制剂对肿瘤的靶向。 该公司围绕白蛋白结合型西罗莫司打造了数条管线，也确实成功在一项罕见癌种中成功推动上市了一项产品（商品名：Fyarro） 罕见的小癌种是血管周围上皮样细胞瘤（PEComa），这一小癌种是软组织肉瘤中的罕见亚型，早先的研究发现，PEComa常常会伴有TSC1和/或TSC2基因突变，而TSC1和/或TSC2基因突变会导致下游mTOR信号通路激活。 那么能否证明在PEComa小癌种中的成功能够在同基因突变条件下的实体瘤中复刻，就成为了拓宽市场的重点。 毕竟PEComa这一小癌种患者人数较少，药品定价也不高，收入相当微薄，今年Q2一季度才卖出了620万美元。 但这次失利的临床恰巧就是TSC1或者TSC2基因突变的实体瘤患者，这也意味着拓宽适应症的尝试基本以失利告终，情势不容乐观。 现在还剩下子宫内膜癌(EEC)和神经内分泌肿瘤(NETs)的数据等待读出。 本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

Combined pipeline and head count changes announced yesterday are expected to extend Aadi Bioscience’s cash runway into “at least” the second half of 2026. Aadi Bioscience’s Fyarro is on track to fail a phase 2 solid tumor trial, leading the biotech to halt the study and lay off 80% of its R&D workforce.The company had been investigating the approved mTOR inhibitor, also known as nab-sirolimus, in the midstage PRECISION1 study in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. But Aadi revealed yesterday that the independent data monitoring committee had decided the trial was unlikely to hit its key goal—namely exceeding an efficacy threshold necessary to support an accelerated approval.It marks a significant setback for Aadi’s wider hopes for Fyarro, the only drug in its pipeline. Only two weeks ago, the California-based company had been suggesting that the data from PRECISION1 had “the potential to demonstrate a meaningful impact on the lives of patients who have already received standard therapies appropriate for their tumor type and stage of disease.”"We are humbled by the effort of the investigators, support staff, and most importantly, the patients and their families who took part in PRECISION1,” Aadi CEO Dave Lennon said in the post-market Aug. 20 release.“While nab-sirolimus showed monotherapy activity in the study population, the trial fell short of delivering what we believe would be required to support an accelerated approval in the broad TSC1/TSC2 inactivating mutations indication,” Lennon added. “We look forward to providing the full trial analysis at a later date.” Aadi has also been evaluating Fyarro in two other phase 2 studies for difficult-to-treat mTOR-driven cancers: neuroendocrine tumors of the lung, gastrointestinal tract and pancreas; and advanced or recurrent endometrioid-type endometrial cancer in combination with Novartis’ Femara.While Aadi is halting the PRECISION1 trial, it said it will continue dosing patients in the neuroendocrine tumor and endometrial cancer studies, although it will stop enrolling new patients. With 10 and 20 patients enrolled in those studies, respectively, Aadi thinks it has enough participants to assess the drug’s efficacy later this year.In relation to this decision, the biotech will lay off 80% of its R&D staff. Fierce has asked Aadi how many employees are set to be impacted.The company had $78.6 million to hand as of the end of June, when it anticipated the money would last into the final months of 2025. The combined pipeline and head count changes announced yesterday are expected to extend the company’s cash runway into “at least” the second half of 2026, it said.As well as “preserving cash” by canning or halting enrollment in its remaining Fyarro trials, Aadi said its other primary focus will be “maximizing its commercial business” through sales of Fyarro in its approved indication of perivascular epithelioid cell tumor. These sales brought in $6.2 million for the company in the second quarter.