JUPITER, Fla. and LEXINGTON, Mass.--(BUSINESS WIRE)--Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) and Agenus Inc. (Nasdaq: AGEN), a leader in discovering and developing novel immunological agents to treat various cancers, today announced that the companies have entered into a royalty financing agreement to support Agenus’ key development initiatives in the ongoing BOT/BAL clinical development program, including its planned confirmatory Phase 3 trial in its lead indication of patients with metastatic, relapsed/refractory colorectal cancer not microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR), who are without active liver metastases (r/r MSS CRC NLM), along with other launch readiness activities..

佛罗里达州朱庇特（JUPITER）和马萨诸塞州列克星敦（LEXINGTON），今天宣布，两家公司签署了特许权使用费融资协议，以支持阿根努斯（Agenus）在正在进行的BOT/BAL临床开发计划中的关键开发举措，包括其计划的3期验证性试验，主要针对无活动性肝转移（r/r MSS CRC NLM）的转移性，复发性/难治性结直肠癌非微卫星不稳定性高（MSI-H）或错配修复缺陷（dMMR）患者，以及其他启动准备活动。。

Under the terms of the agreement, Ligand will pay $75 million to Agenus at closing. In addition, Ligand has the option to invest an additional $25 million on the same terms on a pro rata basis. In return for the initial $75 million payment, Ligand will receive 18.75% of the future royalties and 31.875% of the future milestone payments related to six of Agenus’ clinical-stage partnered oncology programs, including BMS-986442 (Bristol Myers Squibb), AGEN2373 (Gilead Sciences), INCAGN2385 and INCAGN2390 (Incyte), MK-4830 (Merck), and UGN-301 (UroGen Pharma).

根据协议条款，Ligand将在交割时向Agenus支付7500万美元。此外，Ligand有权在相同条件下按比例额外投资2500万美元。作为最初7500万美元付款的回报，Ligand将获得未来版税的18.75%和未来里程碑付款的31.875%，这些款项与Agenus的六个临床阶段合作肿瘤项目有关，包括BMS-986442（Bristol-Myers Squibb），AGEN2373（Gilead Sciences），INCAGN2385和INCAGN2390（Incyte），MK-4830（Merck）和UGN-301（UroGen Pharma）。

Ligand’s portion of the milestones related to these six programs has the potential to exceed $400 million, with royalties in the low single digits. In addition, Ligand will also receive a 2.625% royalty on future global net sales generated by BOT/BAL. The royalties and milestone payments owed to Ligand could be adjusted up or down based upon pre-determined future events and achievements of certain milestones..

Ligand在与这六个项目相关的里程碑中所占的份额有可能超过4亿美元，版税仅为个位数。此外，配体还将从BOT/BAL产生的未来全球净销售额中获得2.625%的特许权使用费。欠配体的特许权使用费和里程碑付款可以根据预先确定的未来事件和某些里程碑的成就进行调整。。

“This partnership with Agenus gives us an interest in multiple oncology products diversified across targets and indications, including royalties on BOT/BAL and several partnered oncology programs being developed by experienced biopharmaceutical companies,” commented Todd Davis, CEO of Ligand. “We are encouraged by Agenus’ progress to move BOT/BAL forward in the metastatic, relapsed/refractory colorectal cancer setting, in addition to other major indications, including pancreatic cancer, lung cancer, and melanoma.

Ligand首席执行官托德·戴维斯（ToddDavis）评论道：“与Agenus的合作使我们对多种肿瘤产品产生了兴趣，这些产品在目标和适应症上都有所不同，包括BOT/BAL的版税以及由经验丰富的生物制药公司开发的几个合作肿瘤学项目。”。“我们对Agenus在转移性，复发性/难治性结直肠癌治疗中取得的进展感到鼓舞，此外还有其他主要适应症，包括胰腺癌，肺癌和黑色素瘤。

This demonstrates the potential value BOT/BAL could deliver to patients, as well as the significant revenue potential of this broad and highly differentiated program. Our seasoned investment team spent significant time and effort conducting diligence on each of these unique and valuable assets.”.

这证明了BOT/BAL可以为患者提供潜在价值，以及这一广泛且高度分化的计划的巨大收入潜力。我们经验丰富的投资团队花费了大量时间和精力对这些独特而有价值的资产进行尽职调查。”。

As part of the agreement, the companies have also agreed to allow Agenus to syndicate up to an additional $125 million, potentially bringing the total capital infusion up to $200 million. This strategic collaboration will further validate BOT/BAL’s potential as a transformative treatment for patients with solid tumor malignancies and enhances Agenus’ ability to advance this promising therapy..

作为协议的一部分，两家公司还同意允许阿根努斯集团额外增加1.25亿美元，这可能使总资本注入达到2亿美元。这一战略合作将进一步验证BOT/BAL作为实体瘤恶性肿瘤患者变革性治疗的潜力，并增强Agenus推进这一有希望的治疗的能力。。

Garo Armen, Chairman and Chief Executive Officer of Agenus, commented, “We are pleased to partner with Ligand, a company that recognizes the paradigm-shifting potential of BOT/BAL in delivering benefit to patients across the solid tumor landscape. Ligand also recognizes the potential impact of our ongoing partnered programs, many of which are showing promise in the clinic.

Agenus董事长兼首席执行官加罗·阿门（Garo Armen）评论道：“我们很高兴与Ligand合作，该公司认识到BOT/BAL在实体瘤领域为患者带来益处的范式转变潜力。Ligand还认识到我们正在进行的合作项目的潜在影响，其中许多项目在临床上显示出前景。

This collaboration enables both parties to benefit in the future potential success of these assets while simultaneously enabling Agenus to accelerate our efforts to bring BOT/BAL to patients in need.”.

这种合作使双方能够从这些资产的未来潜在成功中受益，同时使Agenus能够加速我们的努力，将BOT/BAL带给有需要的患者。”。

Over 900 patients have been treated with BOT/BAL in clinical trials across nine different difficult to treat solid tumor cancers. The novel therapeutic regimen has demonstrated the potential to be combined with chemotherapy and other standard of care therapies, and as an immunotherapy-only combo in CRC, one of the most prevalent solid tumors globally.

在9种不同的难治性实体瘤癌症的临床试验中，已有900多名患者接受了BOT/BAL治疗。这种新的治疗方案已经证明有可能与化疗和其他标准治疗相结合，并且在全球最普遍的实体瘤之一的CRC中作为仅免疫治疗的组合。

In April 2023, Agenus was granted Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the investigation of the BOT/BAL combination in patients with r/r MSS CRC NLM. Patients targeted with this designation are heavily pretreated with standard of care chemotherapy, anti-VEGF and anti-EGFR if RAS wild type..

2023年4月，Agenus被美国食品和药物管理局（FDA）授予快速通道指定，用于调查r/r MSS CRC NLM患者的BOT/BAL组合。针对该名称的患者接受了标准治疗化疗，抗VEGF和抗EGFR if RAS野生型的严重预处理。。

About Agenus

关于Agenus

Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s 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是一家领先的免疫肿瘤学公司，针对癌症和传染病，拥有全面的免疫制剂管道。该公司的使命是通过组合方法，使用广泛的抗体疗法，过继细胞疗法（通过水貂疗法）和佐剂（通过SasioQX），扩大受益于癌症免疫疗法的患者群体。

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 Agenus’ website and social media channels..

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。对投资者可能很重要的信息将定期发布在Agenus的网站和社交媒体渠道上。。

About Botensilimab

关于博滕西林单抗

Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (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是一种研究性多功能抗CTLA-4免疫激活剂（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疗法和研究疗法难治的“冷”肿瘤。

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。。

Over 900 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，已有900多名患者接受了博替尼单抗治疗。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 Agenus Partnered Programs

关于Agenus合作计划

BMS 986-442 is a novel first-in-class anti-TIGIT and CD96 bispecific antibody engineered with an enhanced Fc region for high binding affinity and improved T and NK cell activation. MK-4830 is a potentially first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor.

BMS 986-442是一种新型的一流抗TIGIT和CD96双特异性抗体，具有增强的Fc区，具有高结合亲和力和改善的T细胞和NK细胞活化。MK-4830是靶向免疫球蛋白样转录物4（ILT4）受体的潜在一流人IgG4单克隆抗体。

AGEN2373 is a fully human monoclonal antibody designed to boost the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells. The unique binding properties of AGEN2373 are expected to limit its activity outside of the tumor site and mitigate toxicities that may be associated with systemic activation of CD137 in humans.UGN-301 (zalifrelimab) is a novel, fully human monoclonal immunoglobulin G1 (IgG1) designed to block CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) from interacting with its ligands CD80 and CD86.

AGEN2373是一种完全人类单克隆抗体，旨在通过增强活化免疫细胞中的CD137共刺激信号传导来增强对癌细胞的免疫应答。AGEN2373的独特结合特性有望限制其在肿瘤部位以外的活性，并减轻可能与人类CD137全身激活有关的毒性。UGN-301（zalifrelimab）是一种新型的全人单克隆免疫球蛋白G1（IgG1），旨在阻断CTLA-4（细胞毒性T淋巴细胞相关抗原4）与其配体CD80和CD86的相互作用。

CTLA-4 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market. UroGen has a license to use zalifrelimab via intravesical delivery for treatment of cancers of the urinary tract. INCAGN2385, a novel human Fc silent IgG1 monoclonal antibody targeting LAG-3, blocking binding to MHC II.

CTLA-4是免疫激活的负调节剂，被认为是免疫肿瘤学市场的基础目标。UroGen拥有通过膀胱内递送使用扎利格列单抗治疗泌尿道癌症的许可证。INCAGN2385是一种靶向LAG-3的新型人Fc沉默IgG1单克隆抗体，可阻断与MHC II的结合。

INCAGN3920, a novel recombinant human IgG1 monoclonal antibody targeting TIM-3..

INCAGN3920是一种靶向TIM-3的新型重组人IgG1单克隆抗体。。

About Ligand Pharmaceuticals

关于配体药物

Ligand is a biopharmaceutical company enabling scientific advancement through supporting the clinical development of high-value medicines. Ligand does this by providing financing, licensing our technologies or both. Its business model seeks to generate value for stockholders by creating a diversified portfolio of biopharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure.

Ligand是一家生物制药公司，通过支持高价值药物的临床开发实现科学进步。配体通过提供资金、许可我们的技术或两者来实现这一目标。其商业模式旨在通过创建由高效和低公司成本结构支持的生物制药产品收入流的多元化组合，为股东创造价值。

Ligand’s goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable and diversified manner. Its business model focuses on funding programs in mid- to late-stage drug development in return for economic rights, purchasing royalty rights in development stage or commercial biopharmaceutical products and licensing its technology to help partners discover and develop medicines.

Ligand的目标是为投资者提供一个机会，以盈利和多样化的方式参与生物技术行业的承诺。其商业模式侧重于为中晚期药物开发项目提供资金，以换取经济权利，购买开发阶段或商业生物制药产品的特许使用权，并授权其技术以帮助合作伙伴发现和开发药物。

Ligand partners with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) in order to generate its revenue. Ligand’s Captisol® platform technology is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.

配体与其他制药公司合作，利用他们最擅长的（后期开发，监管管理和商业化）来产生收入。配体的Captisol®平台技术是一种化学修饰的环糊精，其结构旨在优化药物的溶解度和稳定性。

Ligand has established multiple alliances, licenses and other business relationships with the world’s leading biopharmaceutical companies including Amgen, Merck, Pfizer, Jazz, Takeda, Gilead Sciences and Baxter International. For more information, please visit www.ligand.com. Follow Ligand on X @Ligand_LGND..

Ligand与安进（Amgen）、默克（Merck）、辉瑞（Pfizer）、爵士（Jazz）、武田（Takeda）、吉利德（Gilead Sciences）和百特（Baxter International）等世界领先的生物制药公司建立了多个联盟、许可证和其他业务关系。有关更多信息，请访问www.ligand.com。关注X@ligand\u LGND上的配体。。

We use our investor relations website and X as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Investors should monitor our website and our X account, in addition to following our press releases, SEC filings, public conference calls and webcasts..

我们使用我们的投资者关系网站和X作为披露重大非公开信息的手段，并遵守FD法规规定的披露义务。投资者除了关注我们的新闻稿、SEC文件、公开电话会议和网络广播外，还应监控我们的网站和X账户。。

Forward-Looking Statements

前瞻性声明

This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as “plans,” “believes,” “expects,” “anticipates,” and “will,” and similar expressions, are intended to identify forward-looking statements.

本新闻稿包含配体的前瞻性声明，涉及风险和不确定性，并反映了配体截至本新闻稿发布之日的判断。诸如“计划”、“相信”、“期望”、“预期”和“意愿”等词语以及类似的表达，旨在识别前瞻性陈述。

These forward-looking statements include, without limitation, statements regarding: Ligand’s future royalty payments due under its agreement with Agenus, the potential impact of six Agenus-partnered programs with some of the leading biopharma companies in the world, including BMS-986442 (Bristol Myers Squibb), AGEN2373 (Gilead Sciences), INCAGN2385 and INCAGN2390 (Incyte), MK-4830 (Merck), and UGN-301 (UroGen Pharma), the trial and regulatory success of Agenus’ upcoming Phase 3 trial of botensilimab in combination with balstilimab (“BOT/BAL”) for patients with metastatic, refractory colorectal cancer that is not MSI-H/dMMR and who do not have liver metastases, the potential high patient impact, and revenue potential, of BOT/BAL program, the paradigm-shifting potential of BOT/BAL program in delivering benefits to patients across the metastatic solid tumor landscape and in generating significant revenues, Ligand may not receive expected revenue under this agreement or others, Ligand or its partners may not be able to protect their intellectual property, and patents covering certain products and technologies may be challenged or invalidated which could expose Ligand to significant liabilities and have a material adverse effect on the company.

这些前瞻性声明包括但不限于以下声明：配体根据其与Agenus的协议应支付的未来特许权使用费，与世界上一些领先的生物制药公司合作的六个Agenus项目的潜在影响，包括BMS-986442（百时美施贵宝），AGEN2373（吉利德科学），INCAGN2385和INCAGN2390（Incyte），MK-4830（默克）和UGN-301（UroGen Pharma），Agenus即将进行的botensilimab联合balstilimab（“BOT/BAL”）的3期临床试验和监管成功，用于非MSI的转移性难治性结直肠癌患者-H/dMMR和没有肝转移的患者，BOT/BAL计划对患者的潜在高影响和收入潜力，BOT/BAL计划在转移性实体瘤领域为患者提供益处和产生重大收入方面的范式转变潜力，配体可能无法获得本协议或其他协议下的预期收入，配体或其合作伙伴可能无法保护其知识产权，涵盖某些产品和技术的专利可能会受到质疑或无效，这可能使配体承担重大责任，并对公司产生重大不利影响。

The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other risk factors affecting Ligand can be found in prior press release.

未能满足上述任何事项的预期可能会降低Ligand的股价。关于影响配体的这些和其他风险因素的其他信息可以在之前的新闻稿中找到。

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements relating regarding partnered programs, including BMS-986442, AGEN2373, INCAGN2385, INCAGN2390, MK-4830, and UGN-301 and to the use of botensilimab and balstilimab, for instance, statements regarding therapeutic benefit and efficacy, mechanism of action (including validation of mechanism of action), potency, durability, and safety profile (including the absence of specific toxicities) of the Company’s therapeutic candidates; 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，包括与合作项目有关的声明，包括BMS-986442、AGEN2373、INCAGN2385、INCAGN2390、MK-4830和UGN-301，以及与使用botensilimab和balstilimab有关的声明，例如，关于公司候选治疗药物的治疗效果和疗效、作用机制（包括作用机制的验证）、效力、耐久性和安全性（包括没有特定毒性）的声明；以及任何其他包含“可能”、“相信”、“期望”、“期望”、“希望”、“打算”、“计划”、“预测”、“估计”、“意志”、“建立”、“潜力”、“优越性”、“同类最佳”等词语的陈述，以及类似的表达都旨在识别前瞻性陈述。

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 Quarterly Report on Form 10-Q or Annual Report on Form 10-K 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向证券交易委员会提交的10-Q表季度报告或10-K表年度报告中风险因素部分所述的因素。

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发表，除法律要求外，Agenus没有义务更新或修改这些声明。

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。。