Botensilimab

7月13日，免疫肿瘤学公司Agenus（NASDAQ: AGEN）宣布了一项重大的战略调整：停止对晚期转移性微卫星稳定型（MSS）结直肠癌III期BATTMAN研究的资金支持，将全部资源转向高风险早期结肠癌的新辅助治疗。 与此同时，公司完成了一笔最高可达3.4亿美元的私募融资，受此消息提振，其股价周一盘中涨幅一度超过100%。 根据公告，此次融资由Commodore Capital领投，RA Capital、TCGX及Ligand Pharmaceuticals等机构参投，包括8500万美元的即时到账资金，以及未来通过行使认股权证可获得的2.55亿美元。若权证全部行权，这笔资金预计可支撑公司运营至2031年底，足以覆盖关键临床数据的读出节点。 战略重心转移的背后，是Agenus对管线价值的重新评估。此前在NEST和UNICORN两项II期研究中，其核心组合疗法botensilimab联合balstilimab（BOT+BAL）在MSS结肠癌新辅助治疗中展现出令人瞩目的疗效：约60%-70%的患者实现病理缓解，30%达到病理完全缓解（pCR），且在中位随访9至18个月内无复发病例。 为此，Agenus计划启动名为ROBBIN的全球注册性III期试验，入组850名未经治疗的高风险II/III期MSS结肠癌患者，对比新辅助BOT+BAL联合标准治疗与单纯标准治疗的无事件生存期（EFS）。该试验设计已与FDA达成一致，首位患者预计于2027年一季度入组，中期病理缓解数据有望在2027年下半年公布。 对于仍在接受BATTMAN试验治疗的患者，Agenus表示将继续履行相关医疗义务。公司CEO Garo Armen强调，聚焦新辅助治疗是基于现有临床证据强度和患者获益最大化做出的决定，旨在抓住这一长期未被满足的临床需求。 结语： 相比之下，晚期转移性MSS结直肠癌的治疗窗口竞争更为激烈，而新辅助治疗领域在过去20余年尚无突破性疗法获批，美国市场潜在年销售额超70亿美元。

Agenus has scrapped a phase 3 study of its combo therapy in colorectal cancer after just three months in order to go all-in on colon cancer. The biotech launched the late-stage Battman study in April to evaluate a combination of its CTLA-4 inhibitor, botensilimab, and an anti-PD-1 antibody, balstilimab, in unresectable microsatellite stable (MSS) metastatic colorectal cancer (mCRC). The aim was to enroll 830 patients across Canada, France, Australia and New Zealand. At the time, Agenus pointed out that this patient population had been “long considered resistant to immunotherapy.” The company hoped to “quickly” complete enrollment due to the “unprecedented investigator and patient enthusiasm worldwide.” But Agenus has abandoned the study three months later. Scrapping Battman allows the company to focus on Robbin, a planned phase 3 study assessing the same BOT+BAL combo in patients with MSS colon cancer. With around 38,000 addressable patients in the U.S. and no new curative-intent therapies for over two decades, Agenus said it hopes BOT+BAL could unlock a $7 billion sales opportunity in the U.S. alone. The company said it has aligned with the FDA on the design of Robbin, and aims to enroll 850 patients. The trial will be bankrolled by a private placement, also announced this morning, that could ultimately bring in $340 million to the company. The financing was led by Commodore Capital, along with RA Capital Management, TCGX, Invus and Ligand Pharmaceuticals. As for Battman, Agenus said it will “honor its obligations to patients currently receiving treatment” and “work closely with … participating investigators to manage this transition responsibly.” “We have seen neoadjuvant and perioperative immunotherapy improve outcomes in immunologically 'hot' or 'warm' tumors such as melanoma and lung cancer, but MSS colon cancer—a ‘cold’ tumor—has resisted standard checkpoint inhibitors,” Agenus’ Chief Medical Officer Steven O'Day, M.D., said in Monday morning’s release. “With the Robbin trial, we are bringing this regimen to patients with high-risk stage II and stage III MSS colon cancer, where treating an intact tumor gives BOT+BAL its greatest opportunity to generate a durable immune response and improve long-term outcomes,” O'Day added. The BOT+BAL combo ran into trouble earlier this year when a regimen of BOT+BAL with MiNK’s invariant natural killer T cell candidate agenT-797 missed the primary endpoint of a phase 2 study in gastroesophageal cancer. Still, the biotechs insisted at the time that the data support further assessment of the combination.