MIAMI--(BUSINESS WIRE)--Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the “Company”) today announced that we have completed enrollment in our HARMONi clinical trial, a multi-regional Phase III study sponsored by Summit evaluating ivonescimab plus platinum-doublet chemotherapy vs. placebo plus platinum-doublet chemotherapy with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with a 3rd generation EGFR tyrosine kinase inhibitor (TKI).

迈阿密--（商业新闻短讯）--Summit Therapeutics Inc.（纳斯达克：SMMT）（“Summit”，“我们”或“公司”）今天宣布，我们已经完成了HARMONi临床试验的注册，这是一项由Summit赞助的多区域III期研究，评估了ivonescimab加铂双联化疗与安慰剂加铂双联化疗与表皮生长因子受体（EGFR）突变的局部晚期或转移性非鳞状非小细胞肺癌（NSCLC），这些患者在用第三代EGFR酪氨酸激酶抑制剂（TKI）治疗后取得了进展。

HARMONi completed enrolling patients from sites in North America, Europe, and China. This is a clinical setting with a patient population where PD-1 monoclonal antibodies have previously been unsuccessful in Phase III global clinical trials..

HARMONi完成了北美、欧洲和中国站点的患者登记。这是一个临床环境，患者群体中的PD-1单克隆抗体先前在III期全球临床试验中未成功。。

“I would like to sincerely thank the investigators, site coordinators, Team Summit, and, most importantly, the patients around the world who are participating in the HARMONi study,” said Dr. Maky Zanganeh, Chief Executive Officer and President of Summit. “Completing enrollment in the first global study for ivonescimab is a credit to the growing belief in the potential for ivonescimab to make a significant difference in the lives of patients around the world.”.

Summit首席执行官兼总裁Maky Zanganeh博士表示：“我要衷心感谢调查人员、现场协调员、团队峰会，最重要的是，感谢世界各地参与HARMONi研究的患者。”。“完成对ivonescimab的第一项全球研究的登记是对人们越来越相信ivonescimab有可能对世界各地患者的生活产生重大影响的信任。”。

In addition, the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the proposed use of ivonescimab in combination with platinum-based chemotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR mutation, who have experienced disease progression following EGFR-TKI therapy..

此外，美国食品和药物管理局（FDA）已批准快速通道指定，建议使用ivonescimab联合铂类化疗治疗EGFR突变的局部晚期或转移性NSCLC成年患者，这些患者在EGFR-TKI治疗后经历了疾病进展。。

The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. According to the FDA, the purpose is to get important new drugs to patients earlier. A drug that receives Fast Track designation is eligible for some of the following: more frequent meetings with the FDA to discuss the drug’s development plan, more frequent written communication from the FDA, and a rolling review process, allowing the sponsor to submit completed sections of its Biologic License Application (BLA) for review rather than every section at once, though the review by FDA typically begins when the entire application has been submitted.

FDA的快速通道指定旨在促进药物的开发和加速审查，以治疗严重疾病并满足未满足的医疗需求。根据美国食品和药物管理局（FDA）的说法，目的是尽早向患者提供重要的新药。获得快速通道指定的药物符合以下条件：更频繁地与FDA会面以讨论药物的开发计划，更频繁地与FDA进行书面沟通，以及滚动审查过程，允许申办者提交其生物许可申请（BLA）的完整部分以供审查，而不是一次提交每个部分，尽管FDA的审查通常在整个申请提交后开始。

Per the FDA, once a drug receives Fast Track designation, early and frequent communication with the FDA is encouraged throughout the entire drug development and review process; the frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients..

根据FDA的规定，一旦药物获得快速通道指定，在整个药物开发和审查过程中鼓励与FDA进行早期和频繁的沟通；沟通的频率确保了问题和问题得到迅速解决，通常会导致患者更早获得药物批准和使用。。

“Completing enrollment in the HARMONi study represents another step towards our goal of bringing to patients a drug that is intended to improve the quality and potential duration of life for those facing serious unmet medical needs,” stated Robert W. Duggan, Chairman & Chief Executive Officer of Summit.

Summit董事长兼首席执行官罗伯特·达根（RobertW.Duggan）表示：“完成HARMONi研究的注册代表着我们向患者提供一种药物的目标迈出了另一步，该药物旨在改善面临严重未满足医疗需求的患者的质量和潜在寿命。”。

“As our belief in the potential for ivonescimab to make a meaningful, positive difference continues to grow, we are pleased that the FDA has granted Fast Track designation for ivonescimab.”.

“随着我们对ivonescimab产生有意义的积极影响的潜力的信念不断增长，我们很高兴FDA已经批准了ivonescimab的快速通道指定。”。

As a reminder, the HARMONi analysis will include all patients from the HARMONi-A trial who previously received a 3rd generation TKI. HARMONi-A was a single-region, multi-center Phase III clinical trial evaluating ivonescimab plus platinum-doublet chemotherapy vs. placebo plus platinum-doublet chemotherapy with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

作为提醒，HARMONi分析将包括HARMONi-a试验中所有先前接受过第三代TKI的患者。HARMONi-A是一项单区域，多中心III期临床试验，评估ivonescimab加铂双联化疗与安慰剂加铂双联化疗与EGFR突变，局部晚期或转移性非鳞状非小细胞肺癌的疗效，这些非鳞状非小细胞肺癌在EGFR TKI治疗后进展。

HARMONi-A was sponsored by our collaboration partner, Akeso, Inc. (Akeso, HKEX Code: 9926.HK), with data generated and analyzed by Akeso. On May 24, 2024, our partner, Akeso, received marketing authorization in China from the National Medical Products Administration (NMPA) based on the positive dataset associated with HARMONi-A.

HARMONi-A由我们的合作伙伴Akeso，Inc.（Akeso，香港交易所代码：9926.HK）赞助，数据由Akeso生成和分析。2024年5月24日，我们的合作伙伴阿克索（Akeso）根据与HARMONi-A相关的积极数据集，获得了国家医疗产品管理局（NMPA）在中国的上市授权。

HARMONi-A was designed with a primary endpoint of progression-free survival. HARMONi is designed with dual primary endpoints of progression-free survival and overall survival..

HARMONi-A的设计具有无进展生存的主要终点。HARMONi的设计具有无进展生存期和总生存期的双重主要终点。。

About Ivonescimab

关于Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, Japan, Latin America, including Mexico and all countries in Central America, South America, and the Caribbean, the Middle East, and Africa, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule.

Ivonescimab在Summit的许可区域，美国，加拿大，欧洲，日本，拉丁美洲（包括墨西哥和中美洲，南美洲，加勒比，中东和非洲的所有国家）被称为SMT112，在中国和澳大利亚被称为AK112，是一种新型的，潜在的一流研究性双特异性抗体，它将通过阻断PD-1的免疫疗法的作用与阻断VEGF相关的抗血管生成作用结合成一个分子。

Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity when in the presence of both PD-1 and VEGF..

当同时存在PD-1和VEGF时，Ivonescimab以多倍的更高亲和力显示出与每个预期靶标的独特协同结合。。

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro (Zhong, et al, SITC, 2023).

这可以区分ivonescimab，因为与体内正常组织相比，肿瘤组织和肿瘤微环境（TME）中PD-1和VEGF的表达（存在）可能更高。。

This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days (Zhong, et al, SITC, 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets..

这种四价结构，分子的有意新颖设计，以及将这两个靶标引入具有协同结合特性的单一双特异性抗体中，有可能将ivonescimab导向肿瘤组织而不是健康组织。该设计的目的以及6至7天的半衰期（Zhong等，SITC，2023），是为了改善先前确定的疗效阈值，以及与这些目标相关的副作用和安全性。。

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,800 patients have been treated with ivonescimab in clinical studies globally.

Ivonescimab由Akeso Inc.（香港交易所代码：9926.HK）设计，目前正在进行多个III期临床试验。在全球临床研究中，已有1800多名患者接受了ivonescimab治疗。

Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3, with a plan to initiate HARMONi-7 in early 2025.

Summit已开始在非小细胞肺癌（NSCLC）中开发ivonescimab的临床开发，并于2023年开始参加两项多区域III期临床试验HARMONi和HARMONi-3，计划于2025年初启动HARMONi-7。

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib)..

HARMONi是一项III期临床试验，旨在评估ivonescimab联合化疗与安慰剂加化疗相比，对EGFR突变，局部晚期或转移性非鳞状非小细胞肺癌患者进行治疗后，用第三代EGFR TKI（例如osimertinib）治疗进展。。

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.

HARMONi-3是一项III期临床试验，旨在评估ivonescimab联合化疗与pembrolizumab联合化疗治疗一线转移性鳞状NSCLC患者的疗效。

HARMONi-7 is a planned Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS > 50%).

HARMONi-7是一项计划进行的III期临床试验，旨在评估与pembrolizumab单药治疗相比，ivonescimab单药治疗具有高PD-L1表达（PD-L1 TPS>50%）的一线转移性NSCLC患者。

In addition, Akeso has recently had positive read-outs in two single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC, HARMONi-A and HARMONi-2.

此外，Akeso最近在两个单区域（中国）的非小细胞肺癌，HARMONi-A和HARMONi-2的ivonescimab随机III期临床试验中获得了积极的结果。

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-A是一项III期临床试验，评估了依伐昔单抗联合化疗与安慰剂加化疗相比，对EGFR突变，局部晚期或转移性非鳞状非小细胞肺癌患者进行EGFR TKI治疗后的进展情况。

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression (PD-L1 TPS >1%).

HARMONi-2是一项III期临床试验，评估局部晚期或转移性非小细胞肺癌患者PD-L1表达阳性（PD-L1 TPS>1%）的单药治疗依伐昔单抗对单药治疗pembrolizumab的影响。

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting..

Ivonescimab是一种研究性疗法，未经Summit许可区域（包括美国和欧洲）的任何监管机构批准。Ivonescimab于2024年5月被批准在中国上市。Ivonescimab被美国食品和药物管理局（FDA）授予HARMONi临床试验环境的快速通道指定。。

About Summit Therapeutics

关于Summit Therapeutics

Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs..

Summit Therapeutics Inc.是一家生物制药肿瘤公司，专注于患者，医生，护理人员和社会友好药物疗法的发现，开发和商业化，旨在改善生活质量，延长潜在寿命，并解决严重未满足的医疗需求。。

Summit was founded in 2003 and our shares are listed on the Nasdaq Global Market (symbol 'SMMT'). We are headquartered in Miami, Florida, and we have additional offices in Menlo Park, California, and Oxford, UK.

Summit成立于2003年，我们的股票在纳斯达克全球市场上市。我们的总部位于佛罗里达州的迈阿密，在加利福尼亚州的门洛帕克和英国的牛津都设有办事处。

For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX.

有关更多信息，请访问https://www.smmttx.com并在X@SMMT\U TX上关注我们。

Summit Forward-looking Statements

Any statements in this press release about the Company’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company’s product candidates, entry into and actions related to the Company’s partnership with Akeso Inc., the intended use of the net proceeds from the private placements, the Company's anticipated spending and cash runway, the therapeutic potential of the Company’s product candidates, the potential commercialization of the Company’s product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, potential acquisitions, statements about the previously disclosed At-The-Market equity offering program (“ATM Program”), the expected proceeds and uses thereof, and other statements containing the words 'anticipate,' 'believe,' 'continue,' 'could,' 'estimate,' 'expect,' 'intend,' 'may,' 'plan,' 'potential,' 'predict,' 'project,' 'should,' 'target,' 'would,' and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995.

本新闻稿中关于公司未来预期、计划和前景的任何声明，包括但不限于关于公司候选产品的临床和临床前开发、与Akeso Inc.合作的进入和行动、私募净收益的预期用途、公司的预期支出和现金跑道、公司候选产品的治疗潜力、公司候选产品的潜在商业化、临床试验数据的启动、完成和可用性的时间、潜在的上市批准申请提交、潜在的收购、先前在市场股权发售计划（“ATM计划”）中披露的声明、预期收益及其用途的声明以及其他包含“预期”，“相信”，“继续”，“可能”，“估计”，“预期”，“打算”，“可能”，“计划”，“潜力，“预测”、“项目”、“应该”、“目标”、“将会”和类似表述构成了1995年《私人证券诉讼改革法案》含义内的前瞻性陈述。

Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the Company’s ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, industry, or political conditions, including the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent i.

由于各种重要因素，包括公司在ATM计划下出售普通股的能力、影响资本市场的条件、一般经济、行业或政治条件，包括我们对与ivonescimab开发和商业化活动有关的基础数据的评估结果、与监管机构（包括食品和药物管理局）的讨论结果、固有的不确定性，实际结果可能与此类前瞻性声明所示的结果存在重大差异。

Appendix: Glossary of Critical Terms Contained Herein

附录：此处包含的关键术语表

Affinity – Affinity is the strength of binding of a molecule, such as a protein or antibody, to another molecule, such as a ligand.

亲和力-亲和力是分子（如蛋白质或抗体）与另一分子（如配体）结合的强度。

Avidity – Avidity is the accumulated strength of multiple binding interactions.

亲合力–亲合力是多种结合相互作用的累积强度。

Angiogenesis – Angiogenesis is the development, formation, and maintenance of blood vessel structures. Without sufficient blood flow, tissue may experience hypoxia (insufficient oxygen) or lack of nutrition, which may cause cell death.1

血管生成-血管生成是血管结构的发育，形成和维持。如果没有足够的血流，组织可能会出现缺氧（氧气不足）或缺乏营养，这可能导致细胞死亡。1

Cooperative binding – Cooperative binding occurs when the number of binding sites on the molecule that can be occupied by a specific ligand (e.g., protein) is impacted by the ligand’s concentration. For example, this can be due to an affinity for the ligand that depends on the amount of ligand bound or the binding strength of the molecule to one ligand based on the concentration of another ligand, increasing the chance of another ligand binding to the compound.2.

协同结合-当分子上可被特定配体（例如蛋白质）占据的结合位点数量受到配体浓度的影响时，就会发生协同结合。例如，这可能是由于对配体的亲和力取决于配体结合的量或基于另一配体浓度的分子与一个配体的结合强度，从而增加了另一配体与化合物结合的机会。

Immunotherapy – Immunotherapy is a type of treatment, including cancer treatments, that help a person’s immune system fight cancer. Examples include anti-PD-1 therapies.3

免疫疗法-免疫疗法是一种治疗方法，包括癌症治疗，可以帮助人的免疫系统对抗癌症。

Intracranial - Within the cranium or skull.

颅内-在颅骨或颅骨内。

PD-1 – Programmed cell Death protein 1 is a protein on the surface of T cells and other cells. PD-1 plays a key role in reducing the regulation of ineffective or harmful immune responses and maintaining immune tolerance. However, with respect to cancer tumor cells, PD-1 can act as a stopping mechanism (a brake or checkpoint) by binding to PD-L1 ligands that exist on tumor cells and preventing the T cells from targeting cancerous tumor cells.4.

PD-1程序性细胞死亡蛋白1是T细胞和其他细胞表面的一种蛋白质。PD-1在减少无效或有害免疫反应的调节和维持免疫耐受方面起着关键作用。然而，对于癌肿瘤细胞，PD-1可以通过与肿瘤细胞上存在的PD-L1配体结合并阻止T细胞靶向癌性肿瘤细胞而充当停止机制（刹车或检查点）。

PD-L1 – Programmed cell Death Ligand 1 is expressed by cancerous tumor cells as an adaptive immune mechanism to escape anti-tumor responses, thus believed to suppress the immune system’s response to the presence of cancer cells.5

PD-L1程序性细胞死亡配体1由癌细胞表达，作为逃避抗肿瘤反应的适应性免疫机制，因此被认为可以抑制免疫系统对癌细胞存在的反应。5

PD-L1 TPS – PD-L1 Tumor Proportion Score represents the percentage of tumor cells that express PD-L1 proteins.

PD-L1 TPS–PD-L1肿瘤比例评分代表表达PD-L1蛋白的肿瘤细胞的百分比。

PFS – Progression-Free Survival.

PFS–无进展生存期。

RANO – Response Assessment in Neuro-Oncology, the standard for assessing the response of a brain or spinal cord tumor to therapy.

RANO–神经肿瘤学中的反应评估，是评估脑或脊髓肿瘤对治疗反应的标准。

SQ-NSCLC – Non-small cell lung cancer tumors of squamous histology.

SQ-NSCLC–鳞状组织学的非小细胞肺癌肿瘤。

T Cells – T cells are a type of white blood cell that is a component of the immune system that, in general, fights against infection and harmful cells like tumor cells.6

Tetravalent – A tetravalent molecule has four binding sites or regions.

四价–四价分子具有四个结合位点或区域。

Tumor Microenvironment – The tumor microenvironment is the ecosystem that surrounds a tumor inside the body. It includes immune cells, the extracellular matrix, blood vessels and other cells, like fibroblasts. A tumor and its microenvironment constantly interact and influence each other, either positively or negatively.7.

肿瘤微环境-肿瘤微环境是围绕体内肿瘤的生态系统。它包括免疫细胞、细胞外基质、血管和其他细胞，如成纤维细胞。肿瘤及其微环境不断相互作用并相互影响，无论是积极的还是消极的。

VEGF – Vascular Endothelial Growth Factor is a signaling protein that promotes angiogenesis.8

VEGF-血管内皮生长因子是一种促进血管生成的信号蛋白

Summit Therapeutics and the Summit Therapeutics logo are trademarks of Summit Therapeutics Inc. Copyright 2024, Summit Therapeutics Inc. All Rights Reserved.

Summit Therapeutics和Summit Therapeutics徽标是Summit Therapeutics Inc.的商标。版权所有2024，Summit Therapeutics Inc.保留所有权利。

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1 Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105

1涉谷M.血管内皮生长因子（VEGF）及其受体（VEGFR）在血管生成中的信号传导：抗血管生成和促血管生成疗法的关键靶标。基因癌症。2011年12月；2（12）：1097-105

2 Stefan MI, Le Novère N. Cooperative binding. PLoS Comput Biol. 2013;9(6)

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3 US National Cancer Institute, a part of the National Institute of Health (NIH). https://www.cancer.gov/about-cancer/treatment/types/immunotherapy. Accessed April 2024.

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