Balstilimab

Medical Affairs scale-up supports France’s multi-tumor AAC access framework and expanding paid named-patient programs requests LEXINGTON, Mass.--(BUSINESS WIRE)-- Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced the expansion of its global Medical Affairs infrastructure and early-access support capabilities in response to increasing physician-initiated interest regarding authorized access to the investigational immunotherapy combination botensilimab plus balstilimab (BOT+BAL). The expansion reflects increasing interest from treating oncologists worldwide seeking access to BOT+BAL for patients with advanced solid tumors through regulatory-authorized early access pathways, including France’s Authorisation d’Accès Compassionnel (AAC) framework and paid named patient programs (NPPs) where permitted. This interest follows a series of recent scientific milestones, including peer-reviewed publications, clinical data presentations at major international scientific meetings and the recent expansion of reimbursed compassionate access for BOT+BAL under France’s AAC framework that now includes three tumor types. This scientific and regulatory validation has translated into real-world physician action. Patients have already been treated with BOT + BAL through regulatory-authorized paid named patient programs in multiple countries across South and Central America and Europe, including the United Kingdom and Switzerland, where permitted by local regulations. These requests have originated from treating oncologists managing patients with advanced solid tumors who have exhausted available standard-of-care treatment options, and require coordinated Medical Affairs oversight to support compliant access, safety monitoring, and regulatory alignment across regions. Botensilimab is an Fc-enhanced multifunctional anti-CTLA-4 antibody, and BAL is an PD-1 inhibitor. Together, BOT+BAL is a chemotherapy- and radiation-free immunotherapy regimen currently being evaluated in clinical trials. Authorized Early Access Pathways Agenus’ early-access support is structured around two complementary authorized pathways: • France’s AAC framework, under which BOT+BAL is provided in hospitals under a nationally standardized protocol and is reimbursed for eligible patients across three advanced solid tumors: MSS mCRC without active liver metastases, platinum-refractory or platinum-resistant ovarian cancer, and advanced or metastatic soft-tissue sarcomas; and • Paid named-patient programs (NPPs) in select countries where permitted and available under each country’s regulatory framework. These programs are physician-initiated and patient-specific and may involve out-of-pocket payment and/or special insurance arrangements depending on local regulations and individual coverage decisions. “As clinical evidence for botensilimab plus balstilimab continues to mature, we are seeing increasing inquiries from physicians seeking information about access for patients with limited therapeutic alternatives,” said Garo Armen PhD, Chairman and Chief Executive Officer of Agenus. “Expanding our global Medical Affairs infrastructure ensures that this interest is supported with the appropriate scientific rigor, safeguards, while positioning the organization for disciplined execution across authorized access pathways and late-stage clinical development.” As physician engagement and access requests have increased, Agenus has expanded its Medical Affairs infrastructure to ensure that requests are supported responsibly and in alignment with applicable regulatory guidelines. Medical Affairs plays a central role in facilitating scientific exchange, coordinating appropriate access requests where permitted, supporting pharmacovigilance and safety reporting, and enabling structured collection of real-world safety and outcomes data where applicable. BOT+BAL remains investigational and is not approved for commercial marketing in France or elsewhere. In the United States, access to BOT+BAL is currently limited to participation in clinical trials, consistent with applicable regulatory requirements for investigational therapies. 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 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. 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 is committed to responsible patient access to investigational medicines through clinical trials and regulatory-authorized early-access mechanisms. In France, BOT+BAL is available only through the ANSM-authorized AAC framework under a nationally validated protocol, with full government reimbursement for eligible patients treated in hospital. Global access pathways Until marketing authorization is granted, BOT+BAL is accessible only through clinical trials including the planned Phase 3 BATTMAN trial in refractory MSS colorectal cancer and authorized early access mechanisms where permitted and available under each country’s regulatory framework. For eligible French patients treated in hospital under AAC meeting the pre-defined criteria, BOT+BAL is fully reimbursed by France’s national health system (Assurance Maladie). Reimbursement is structured as a single, upfront, course-based reimbursement per patient that covers the patient’s full course of therapy according to the national AAC protocol, rather than on a per-dose basis. Once a patient is authorized and treatment is initiated under the protocol, full course of treatment and all subsequent administrations are supplied without additional product charges. In line with AAC requirements, the maximum indemnity applicable to BOT+BAL is declared to the relevant French authorities. Outside France, access may be available in select countries through paid named-patient programs, which may involve out-of-pocket payment and/or special insurance arrangements depending on local regulations and individual coverage decisions. About BATTMAN CO.33 Phase 3 Trial Agenus, in collaboration with the Canadian Cancer Trials Group (CCTG), is initiating a global Phase 3 registrational trial evaluating botensilimab (BOT) plus balstilimab (BAL) versus best supportive care (BSC) in patients with refractory, unresectable microsatellite stable (MSS)/mismatch repair proficient (pMMR) colorectal cancer. The study will be conducted as an international cooperative group trial, led by CCTG and supported by academic networks including AGITG (Australasian Gastro-Intestinal Trials Group) and PRODIGE (France), which comprises Unicancer, GERCOR, and FFCD. The trial will enroll approximately 800 patients across more than 100 sites in Canada, France, Australia, and New Zealand. About Botensilimab (BOT) Botensilimab (BOT) is a human Fc enhanced multifunctional anti-CTLA-4 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 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. Approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. In France, botensilimab is accessible only through the ANSM-authorized AAC framework when used as BOT+BAL under the national protocol described above. About Balstilimab (BAL) Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types. In France, balstilimab is accessible only through the ANSM-authorized AAC framework when used as BOT+BAL under the national protocol described above. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding botensilimab and balstilimab, early access pathways, clinical development plans (including BATTMAN), and expected regulatory and clinical timelines, and any other statements containing the words “may,” “believes,” “expects,” “anticipates,” “hopes,” “intends,” “plans,” “forecasts,” “estimates,” “will,” and similar expressions intended to identify forward-looking statements. 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 2024, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. 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. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Source: Agenus Inc. Investors 917-362-1370 | investor@agenusbio.com Media 781-674-4422 | communications@agenusbio.com

2026年1月，免疫肿瘤企业Agenus宣布与Zydus Lifesciences达成1.41亿美元战略合作，推动其免疫治疗组合BOT+BAL的全球开发及商业化。交易包括7500万美元现金、1600万美元股权投资及最多5000万美元里程碑付款，Zydus还获得该组合在印度和斯里兰卡的独家权利。 Agenus保留美国生产能力，支持其全球III期注册试验BATTMAN在MSS结直肠癌领域的推进。BOT+BAL此前在临床中显示出显著生存优势，合作将进一步强化其供应链及全球商业化布局。 有问题，问星光智能体！ 人类基地：惊天反转！“微塑料恐慌”是场科学乌龙？《自然》论文遭同行狠批！ 投资亮点 一、产品价值验证与全球化加速 BOT+BAL组合是Agenus在免疫肿瘤领域的核心产品，已在晚期MSS结直肠癌患者中展现出中位总生存期21个月、2年生存率达42%的卓越数据，远超传统免疫疗法对“冷瘤”的治疗效果。此次交易代表全球市场，尤其是新兴市场（如印度）的潜在合作方已充分认可其临床价值。 Zydus获得该组合在印度与斯里兰卡的独家商业化权利，将极大推动Agenus在发展中国家的市场渗透，同时Agenus可通过5%的销售提成（royalty）长期受益。 二、释放非核心资产、优化现金流 Agenus将位于加州的两处生物药生产设施出售给Zydus，获得7500万美元现金，进一步改善其资产负债表和现金流状况，有助于支撑其III期临床和注册申报开支。 此外，Agenus无需完全退出制造能力，而是通过本次协议保留长期生产配额（committed capacity），实现“资产轻”但“控制强”的灵活制造策略，降低运营负担的同时保障药物供应。 三、通过股权投资绑定战略合作关系 Zydus同时以每股7.5美元价格，认购了Agenus价值1600万美元的股份，成为战略股东。这一安排既体现出Zydus对BOT+BAL组合长期前景的信心，也增强了双方合作的粘性与协同动力。 四、未来里程碑收入与产能收益具潜力 该协议还包含最高5000万美元的产能激励（milestone payments），未来随着BOT+BAL进入商业化阶段或临床试验扩大，Agenus有望获得额外现金流补充。 而Zydus新成立的Zylidac Bio LLC不仅承接制造设施，还将面向全球提供CDMO服务，为其自身打开新的营收渠道。 五、Agenus战略聚焦，提升执行力 本次合作使Agenus能集中资源推进其III期注册临床试验BATTMAN项目，这是面向MSS结直肠癌的一项关键性全球注册研究，预计覆盖100+国际临床中心。此次交易正值其商业化前夜，及时补充资源和产能，有助于其加速向全球监管申报与早期支付机制（如法国AAC）推进。 Agenus的价值分析 一、产品优势：差异化免疫组合疗法BOT+BAL 核心产品为BOT（Botensilimab）+ BAL（Balstilimab）组合，针对传统免疫治疗无效的“冷瘤”（如MSS结直肠癌）展现出显著疗效。 多项临床试验（包括NEST-1、NEOSIS、BATTMAN）数据支持其在多种实体瘤（结直肠癌、卵巢癌、软组织肉瘤等）中具有深度和持久的应答率。 可用于新辅助治疗、三线及更晚期治疗，具备较强的适应症扩展潜力。 二、技术优势：创新靶点机制+ 免疫系统双向激活 1、BOT为增强型Fc抗体，可激活先天+适应性免疫，包括T细胞、髓系细胞和记忆免疫反应。 2、BAL为高亲和力PD-1单抗，具备良好的安全性和耐受性，且与BOT形成互补协同。 3、重点突破“免疫耐药肿瘤”，填补目前PD-1/PD-L1疗法无效人群的治疗空白。 三、平台优势：完整的端到端免疫药物研发体系 1、拥有自研抗体库、细胞治疗平台、疫苗佐剂平台，形成组合式创新研发策略。 2、具备临床前至III期、全球临床操作、以及GMP生产设施（部分已转让但保留产能）。 3、多管线协同，具备开发下一代免疫组合药的强大平台能力。 四、服务优势：多样化患者可及路径 1、在法国、美国等国家开通早期使用通道（如AAC），并由国家医保全额报销（法国）。 2、开展“付费命名患者计划”，在尚未获批国家通过商业化路径提供药品，提升可及性。 3、提供清晰的患者教育与用药资源，强调对患者结果负责的企业文化。 五、商业模式：核心产品主导+ 灵活合作 1、核心管线BOT+BAL由Agenus主导开发与全球布局，但通过与Zydus、Ligand等企业合作，释放非核心资产、引入资金并拓展区域市场。 2、高度灵活的交易结构，包括股权、产能换现金、授权换提成等方式，优化资源配置。 3、通过CDMO、License-out等方式，建立稳定的现金流支撑创新投入。 六、医疗价值：面向“免疫盲区”人群的转化疗法 1、针对目前免疫治疗获益较低的MSS结直肠癌、复发难治卵巢癌、软组织肉瘤等人群提供新疗法。 2、以“免疫组合治疗”理念，推动从一线至新辅助等全治疗周期的应用，提升患者长期生存。 3、有望替代传统放化疗、减少手术需求，改变部分实体瘤的治疗范式。 七、未来前景：数据驱动注册、全球化商业加速 1、正在推进全球注册III期试验（BATTMAN），预计将成为MSS CRC领域首个获批免疫疗法。 2、法国、加拿大、澳洲等国临床基地已激活，全球化布局逐步落地。 3、公司愿景是成为冷瘤免疫治疗的领导者，预计BOT+BAL首个适应症峰值销售潜力超10亿美元，后续有望在更多瘤种中复制成功路径。  癌症免疫循环 一、核心科学理念：调动人体免疫系统抗癌 与传统治疗手段（化疗、放疗、手术）不同，Agenus的免疫疗法（IO）目标是利用人体自身免疫系统识别并清除癌细胞，同时保护正常细胞，减少长期副作用和并发症。 其治疗逻辑紧密围绕“癌症免疫循环（Cancer Immunity Cycle）”设计，分为以下几个阶段： 1、识别与启动（Priming & Activation）：肿瘤通过多种机制“伪装”以逃避免疫系统。Agenus的药物能够“揭示”隐藏肿瘤，激活T细胞等免疫因子。 2、持续攻击与清除（Sustained Attack & Elimination）：其免疫调节剂可维持免疫活性，直到彻底清除癌细胞并建立免疫记忆，防止复发。 二、关键技术组合：BOT + BAL 联合疗法 Agenus目前的明星产品组合为： 1、Botensilimab (BOT)：一种Fc结构增强型抗CTLA-4抗体，不仅激活T细胞，还可重新编程抑制性免疫微环境，提高对“冷瘤”的免疫应答。 2、Balstilimab (BAL)：一种高亲和力的PD-1抑制剂，可阻断肿瘤诱导的T细胞“疲劳”，恢复其攻击能力。 这两种免疫检查点抑制剂协同作用，可实现更深层次、更持久、更广谱的抗肿瘤反应。该组合正在进行全球III期临床（BATTMAN试验），用于MSS型结直肠癌治疗。 三、科学创新点总结 项目 描述 治疗机制 不依赖直接杀伤肿瘤，而是激发机体自身免疫力清除癌细胞，具有“训练+记忆”功能。 靶点技术 创新性双靶点（CTLA-4 + PD-1）联用，增强免疫激活同时降低毒副作用。 治疗人群 针对传统疗法效果不佳的“冷瘤”如MSS 结直肠癌、卵巢癌、软组织肉瘤等。 疗效特征 临床研究显示治疗反应更深、更持久，部分患者可达完全缓解（CR）或病理完全缓解（pCR）。 长期防复发 强调“免疫记忆”机制，治疗后仍能维持抗肿瘤警觉性，有效减少复发率。 四、平台化布局与战略协同 Agenus的IO 管线围绕免疫循环多个环节布局，除了BOT+BAL组合，还拥有多个早期单抗、联合免疫方案、疫苗佐剂平台等技术储备。 致力于实现组合免疫治疗平台化发展，并推动多适应症拓展。 与多国临床试验网络及战略伙伴合作，加快临床开发与注册步伐。 Agenus的Pipeline 一、总体概况：布局全面、靶点创新、组合策略清晰 Agenus作为一家临床阶段的免疫肿瘤公司，其产品管线围绕癌症免疫循环多个关键环节布局，开发具有互补机制的免疫疗法。核心特色是： 1、多靶点联合策略（CTLA-4 + PD-1为核心） 2、多适应症并行推进，重点在“冷瘤”领域 3、多个药物进入2期/3期，具备中后期商业转化潜力 二、明星产品组合：BOT + BAL 1、药物信息： Botensilimab（AGEN1181）：Fc增强型抗CTLA-4抗体，具多机制增强免疫激活 Balstilimab：人源化PD-1单抗，已验证安全性良好 2、临床布局： 适应症 项目名称 阶段 状态 MSS转移性结直肠癌（四线以上） BATTMAN III期 进行中（全球多中心） MSS mCRC 非肝转移（三线） C-800-25 II期 已完成招募 新辅助mCRC NEST / 24-389 II期 已招募/ 招募中 胰腺癌（联合化疗） C-800-22 II期 已完成招募 多种肿瘤新辅助治疗 NEOASIS II期 招募中 一线MSS CRC UNICORN / FOLFOX组合 II期 招募中 复发/难治黑色素瘤 未命名 II期 开展中 亮点：该组合在MSS-CRC（一种传统免疫耐药瘤种）中展现突破性疗效，具备First-in-Class潜力。 三、多靶点免疫资产布局（早期产品） 药物代号 靶点 联合策略 适应症 阶段 AGEN2373 CD137激动剂 ± BOT 实体瘤、黑色素瘤 I/II期 AGEN1571 抗ILT-2 ± BOT/BAL 实体瘤 I期 AGEN1777 双特异抗体（TIGIT × CD96） + BAL 实体瘤 I期 AGEN1423 CD73 × TGF-β 双靶点抗体 单药 实体瘤 I期 AGEN1949 OX40激动剂 单药 实体瘤 I期 INCAGN1876 GITR激动剂 单药 实体瘤 I期 亮点：Agenus通过多个激动性抗体、双靶点抗体等新兴免疫机制补强产品线，有望实现未来免疫组合个性化治疗。 四、平台策略与临床转化特色 组合治疗为主线：几乎所有资产均为联合疗法开发，强调协同机制。 适应症聚焦“免疫盲区”：优先布局传统免疫无效癌种（如MSS CRC、胰腺癌等）。 新辅助治疗探索活跃：尝试通过免疫疗法提升早期肿瘤治疗反应率与根治率。 合作广泛：与CCTG、Weill Cornell、Duke、MSKCC、City of Hope等全球顶尖肿瘤中心合作开展临床。 欲深入了解更多行业洞察，请扫以下二维码加入社群：                  公司已完成项目 星际微光已完成的项目（截至2023.9，仍在继续......）  圆满中秋 | 星际微光七年完成100个咨询项目 咨询、调研、PR、投资、融资、营销、技术转化项目需求请扫码联系我们： 点击“阅读原文”，看看：全身MRI是虚假的安全感吗？