LEXINGTON, Mass.--(BUSINESS WIRE)--Agenus Inc. (NASDAQ: AGEN), a leader in developing novel immunological agents to treat various cancers, today announced the results of its end-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA), for the advancement of its immunotherapy combination, botensilimab (BOT) and balstilimab (BAL), for the treatment of adult patients with relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC) with no active liver metastases (NLM)..

马萨诸塞州列克星敦市（商业新闻短讯）--开发用于治疗各种癌症的新型免疫药物的领导者Agenus Inc.（NASDAQ:AGEN）今天宣布了与美国食品和药物管理局（FDA）举行的第二阶段（EOP2）会议的结果，以推进其免疫治疗组合botensilimab（BOT）和balstilimab（BAL），用于治疗无活动性肝转移（NLM）的复发/难治性微卫星稳定型结直肠癌（r/r MSS CRC）成年患者。。

Key Outcomes of the EOP2 Meeting:

EOP2会议的主要成果：

Dosing Regimen: Agenus gained agreement on the proposed BOT/BAL combination dosing regimen of 75mg BOT once every 6 weeks for up to 4 doses in combination with 240mg BAL once every 2 weeks for up to 2 years.

给药方案：Agenus同意拟议的BOT/BAL联合给药方案，每6周一次75mg BOT，最多4剂，每2周一次240mg BAL，最多2年。

Randomized Phase 2 Interim Data: Topline interim data suggest best activity seen at 75 mg BOT/240mg BAL combination (ORR 19.4%; 6-month survival rate of 90%; data continues to mature).

随机2期中期数据：Topline中期数据显示75 mg BOT/240mg BAL组合的最佳活性（ORR 19.4%；6个月生存率90%；数据继续成熟）。

Accelerated Approval: FDA advised against submission of these results in support of an Accelerated Approval based on their view that objective response rates may not translate to survival benefit.

加速批准：FDA建议不要提交这些结果，以支持加速批准，因为他们认为客观缓解率可能无法转化为生存获益。

Phase 3 Protocol Design: The FDA recommended the inclusion of a BOT monotherapy arm at Agenus’ discretion in the Phase 3 study.

第三阶段方案设计：FDA建议在第三阶段研究中由Agenus自行决定纳入BOT单药治疗组。

Dr. Steven O’Day, Agenus’ Chief Medical Officer, stated, “Based on the high level of enthusiasm from significant numbers of global clinical experts and the promising clinical activity we have seen in the Phase 1 and 2 studies, our commitment to seek all possible pathways to make BOT/BAL available to patients is unwavering.

Agenus首席医疗官Steven O'Day博士表示：“基于大量全球临床专家的高度热情以及我们在第一阶段和第二阶段研究中看到的有希望的临床活动，我们坚定不移地致力于寻求所有可能的途径，使患者可以使用BOT/BAL。

This includes exploring opportunities to partner in the U.S. to accomplish a successful Phase 3 trial.”.

。

Agenus previously disclosed data from the Phase 1 trial, which showed an overall response rate (ORR) of 23% in the 77 MSS mCRC patients without active liver metastases, with a median follow up of 13.6 months. The estimated 6-month, 12-month and 18-month overall survival (OS) rates were 86%, 71%, and 62%, respectively.

Agenus先前披露了第一阶段试验的数据，该试验显示77名无活动性肝转移的MSS mCRC患者的总有效率（ORR）为23%，中位随访时间为13.6个月。估计的6个月，12个月和18个月总生存率（OS）分别为86%，71%和62%。

The estimated median OS was 21.2 months..

估计中位OS为21.2个月。。

Topline interim data (below) from the Phase 2 trial are showing trends consistent with the Phase 1 study, including an ORR of 19.4% and 6-month survival rate of 90% for the BOT 75mg/BAL combination. The safety profile was manageable and no new signals were observed. Agenus plans to continue future discussions with FDA as the Phase 2 data mature and will present these data in totality at an upcoming medical conference..

来自第二阶段试验的Topline中期数据（下文）显示出与第一阶段研究一致的趋势，包括BOT 75mg/BAL组合的ORR为19.4%，6个月生存率为90%。安全性是可控的，没有观察到新的信号。随着第二阶段数据的成熟，Agenus计划继续与FDA进行未来的讨论，并将在即将举行的医学会议上全面介绍这些数据。。

Topline Interim Phase 2 Data

Topline过渡阶段2数据

BOT + BAL

BOT+BAL

75 mg

75毫克

(n= 62)

（n=62）

BOT+BAL

BOT+BAL

150 mg

150毫克

(n=61)

（n=61）

BOT

机器人

75 mg

75毫克

(n=38)

（n=38）

BOT

机器人

150 mg

150毫克

(n=40)

（n=40）

SOC

SOC公司

(n=33)

（n=33）

ORR %

ORR%

(95% CI)

（95%置信区间）

n/nn

编号：nn

19.4*

19.4*

(10.4, 31.4)

(10.4, 31.4)

12/62

12/62

8.2

8.2

(2.7, 18.1)

(2.7, 18.1)

5/61

5/61

0

0

(0.0, 9.3)

(0.0, 9.3)

0/38

0/38

7.5

7.5

(1.6, 20.4)

3/40

0

0

(0.0, 10.6)

(0.0, 10.6)

0/33

0/33

Follow-Up (m)

后续（m）

Mean (SD)

平均值（SD）

Range

范围

9.5

9.5

(2.77)

(2.77)

1.2, 15.7

1.2, 15.7

9.1

9.1

(3.25)

(3.25)

0.1, 16.6

0.1, 16.6

7.8

7.8

(4.37)

(4.37)

0.2, 14.8

0.2, 14.8

8.2

8.2

(4.53)

(4.53)

0.7, 17.1

0.7, 17.1

5.5

5.5

(5.30)

0.0, 13.0

*Pending confirmation of two additional responses in 75mg BOT + BAL arm. No responses are pending confirmation in other arms.

*等待75mg BOT+BAL臂中另外两个响应的确认。其他部门尚未确认任何答复。

​These results are particularly meaningful, as the landscape of MSS colorectal cancer treatment has seen little advancement leaving a significant gap in effective therapies for patients.

​这些结果特别有意义，因为MSS结直肠癌治疗的前景几乎没有进展，在患者的有效治疗方面留下了巨大差距。

“MSS colorectal cancer, representing approximately 95% of colorectal cancer cases, remains a disease setting with substantial unmet need and is considered to be one of the most challenging types of cancer due to its high incidence and mortality rates,” said Michael Sapienza, Chief Executive Officer of Colorectal Cancer Alliance.

“MSS结直肠癌约占结直肠癌病例的95%，仍然是一种需要大量满足的疾病，由于其高发病率和死亡率，被认为是最具挑战性的癌症类型之一，”结直肠癌联盟首席执行官迈克尔·萨皮恩扎说。

“The rapidly growing number of diagnoses in younger individuals is particularly alarming. There is an urgent need for new treatment options that can transform the trajectory of MSS colorectal cancer and provide lasting benefits for patients.”.

“年轻人的诊断数量迅速增长尤其令人担忧。迫切需要新的治疗方案，可以改变MSS结直肠癌的发展轨迹，为患者提供持久的益处。”。

In addition to the progress in the U.S., Agenus is advancing its efforts to bring BOT/BAL to patients in Europe. Engagements with the European Regulatory Authority to explore registration paths are scheduled for later this summer. These discussions aim to align on the regulatory path for approval of the BOT/BAL combination in Europe..

除了在美国取得的进展外，Agenus正在努力将BOT/BAL带给欧洲的患者。计划于今年夏天晚些时候与欧洲监管局（European Regulatory Authority）接洽，探索注册途径。这些讨论旨在调整欧洲BOT/BAL组合批准的监管路径。。

Other areas of BOT/BAL clinical development:

BOT/BAL临床开发的其他领域：

Agenus continues to pursue opportunities for BOT/BAL development in earlier lines of CRC and other tumor types where BOT/BAL has demonstrated clinical activity, such as lung, melanoma, and pancreatic cancers. The company expects to present data from some of these programs at future medical congresses, including BOT/BAL in sarcoma at European Society for Medical Oncology (ESMO) in September 2024..

Agenus继续在早期的CRC和其他肿瘤类型中寻求BOT/BAL发展的机会，其中BOT/BAL已显示出临床活性，例如肺癌，黑色素瘤和胰腺癌。该公司预计将在未来的医学大会上提供其中一些项目的数据，包括2024年9月在欧洲医学肿瘤学会（ESMO）举行的肉瘤BOT/BAL。。

About Botensilimab

关于博滕斯利马

Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies.

Botensilimab是一种人类Fc增强的CTLA-4阻断抗体，旨在增强先天性和适应性抗肿瘤免疫反应。其新颖的设计利用作用机制将免疫治疗的益处扩展到“冷”肿瘤，这些肿瘤通常对标准治疗反应不佳或对常规PD-1/CTLA-4疗法和研究疗法无效。

Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses..

Botensilimab通过引发和激活T细胞，下调肿瘤内调节性T细胞，激活骨髓细胞和诱导长期记忆反应来增强多种肿瘤类型的免疫反应。。

Approximately 1100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316..

在1期和2期临床试验中，约有1100名患者接受了botensilimab治疗。单独使用Botensilimab或与Agenus的研究性PD-1抗体balstilimab联合使用，已显示出对9种转移性晚期癌症的临床反应。有关botensilimab试验的更多信息，请访问www.clinicaltrials.gov，标识符为NCT03860272，NCT05608044，NCT05630183和NCT05529316。。

About Colorectal Cancer

关于结直肠癌

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, and is estimated to be the number one killer of men aged 50 and above and second leading killer of women in the same age category. Microsatellite stable (MSS) colorectal cancer is the most prevalent form of the disease, representing approximately 95% of patients with colorectal cancer.

大肠癌（CRC）是美国癌症死亡的第二大原因，估计是50岁及以上男性的头号杀手，也是同年龄段女性的第二大杀手。微卫星稳定（MSS）结直肠癌是该疾病最普遍的形式，约占结直肠癌患者的95%。

Survival remains poor for advanced disease, and the burden is shifting to a younger population. Alarmingly, from 1995 to 2019, the number of patients under the age of 55 who were diagnosed with CRC in the United States nearly doubled..

晚期疾病的生存率仍然很低，负担正在转移到年轻人群身上。令人震惊的是，从1995年到2019年，美国被诊断患有结直肠癌的55岁以下患者人数几乎翻了一番。。

About Agenus

Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx).

Agenus是一家领先的针对癌症的免疫肿瘤学公司，拥有全面的免疫制剂管道。该公司成立于1994年，其使命是通过多种抗体疗法，过继性细胞疗法（通过水貂疗法）和佐剂（通过SANIQX），通过组合方法扩大受益于癌症免疫疗法的患者群体。

Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels..

Agenus在商业和临床cGMP制造设施、研究和发现以及全球临床运营领域拥有强大的端到端开发能力。Agenus总部位于马萨诸塞州列克星敦。有关更多信息，请访问www.agenusbio.com或@Agenus\u bio。对投资者可能重要的信息将定期发布在我们的网站和社交媒体渠道上。。

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words 'may,' 'believes,' 'expects,' 'anticipates,' 'hopes,' 'intends,' 'plans,' 'forecasts,' 'estimates,' 'will,' “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements.

本新闻稿包含根据《联邦证券法》安全港条款做出的前瞻性声明，包括关于其botensilimab和balstilimab计划的声明、预期监管时间表和备案，以及任何其他包含“可能”、“相信”、“预期”、“预期”、“希望”、“打算”、“计划”、“预测”、“估计”、“意志”、“建立”、“潜力”、“优势”、“一流”等字样的声明，以及类似的表达都旨在识别前瞻性声明。

These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2023, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission.

这些前瞻性陈述受到可能导致实际结果产生重大差异的风险和不确定性的影响。这些风险和不确定性包括我们最近的2023年10-K表年度报告风险因素部分所述的因素，以及随后向美国证券交易委员会提交的10-Q表季度报告。

Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law.

Agenus提醒投资者不要过分依赖本新闻稿中的前瞻性声明。这些声明仅在本新闻稿发布之日有效，除法律要求外，Agenus不承担更新或修订声明的义务。

All forward-looking statements are expressly qualified in their entirety by this cautionary statement..

本警示声明明确限定了所有前瞻性声明的全部内容。。