SEMA4A

- Data demonstrates potential for IO-108 to enhance immune activation and overcome resistance in advanced solid tumors as a monotherapy and in combination with pembrolizumab - PALO ALTO, CA, November 21, 2024 -- Immune-Onc Therapeutics, Inc. (“Immune-Onc”), a private clinical-stage biopharmaceutical company advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, today announced the publication of Phase 1 dose-escalation study results of IO-108, its first-in-class antibody targeting LILRB2 (also known as ILT4), in the Journal for ImmunoTherapy of Cancer (JITC), the peer-reviewed, online journal of the Society for Immunotherapy of Cancer (SITC). The paper, entitled “Phase 1 Dose Escalation Study of IO-108, an Anti-LILRB2 Antibody, in Patients with Advanced Solid Tumors,” details the safety, tolerability, preliminary efficacy, pharmacokinetics, immunogenicity, and pharmacodynamic biomarker results from 25 patients with advanced solid tumors enrolled in a first-in-human study of IO-108 as a monotherapy and in combination with pembrolizumab, an anti-PD-1 antibody. In the IO-108 monotherapy cohort, the overall response rate was 9%, with one patient achieving a durable complete response (CR) for over two years. The CR was observed in a patient with treatment-refractory Merkel cell carcinoma whose prior treatment included two lines of immunotherapy (pembrolizumab, followed by a combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4)). Among 13 efficacy-evaluable patients treated with the combination of IO-108 plus pembrolizumab, 3 patients (2 cholangiocarcinoma and 1 colon cancer, all microsatellite-stable cancer types that typically do not respond to T-cell checkpoint inhibitors) had a partial response (23%). Biomarker analysis revealed pharmacodynamic changes consistent with increased T-cell infiltration in tumors, indicating an activated tumor microenvironment in patients with clinical benefit in both monotherapy and combination therapy. Results also demonstrated that IO-108 was well-tolerated at all dose levels, with no dose-limiting toxicities observed. “The durable responses observed in this heavily pretreated patient population underscore the therapeutic potential of IO-108 as both a monotherapy and in combination with T-cell immune checkpoint inhibitors,” said IO-108 Phase 1 investigator and first author of the paper, Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. “These findings provide compelling evidence that targeting myeloid-cell immune checkpoint LILRB2 offers a novel and promising approach to cancer treatment.” “We are very proud of our positive data published in the Journal for ImmunoTherapy of Cancer (JITC),” said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. “Our data suggest that IO-108 could play a pivotal role as a monotherapy and combination therapy with T-cell immune checkpoint inhibitors and support the broader clinical exploration of IO-108 as a versatile therapeutic option for patients with advanced solid tumors.” Immune-Onc is advancing the development of IO-108 in a Phase 1b/2 global, randomized study that is part of Roche’s Morpheus-Liver program. The study will evaluate IO-108 in combination with atezolizumab and bevacizumab versus atezolizumab and bevacizumab, the standard of care in patients with locally advanced, metastatic and/or unresectable liver cancer with no prior systemic treatment. The study’s primary endpoint is objective response rate, and key secondary endpoints include progression-free survival and overall survival. ABOUT IO-108 IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards the myeloid checkpoint, LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A and CD1d. Clinical data from the U.S. Phase 1 dose escalation study of IO-108 (NCT05054348) was presented at the 2023 American Association for Cancer Research annual meeting and demonstrated a favorable safety profile and encouraging clinical benefit utilizing IO-108 as a monotherapy and in combination with anti-PD-1 across multiple tumor types. IO-108 is being studied in several expansion cohorts in adult cancer patients as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab). A global, randomized Phase 1b/2 study is underway to evaluate IO-108 in combination with atezolizumab and bevacizumab as a potential first-line therapy for hepatocellular carcinoma (HCC). ABOUT IMMUNE-ONC THERAPEUTICS, INC. Immune-Onc Therapeutics Inc. (“Immune-Onc”) is a private, clinical-stage biopharmaceutical company developing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors. Immune-Onc has a differentiated pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB). Immune-Onc’s focused platform approach has led to the development of several promising therapeutics across various stages of development. Those include IO-108, an antagonist antibody targeting LILRB2 (also known as ILT4), in Phase 1b/2 clinical development for solid tumors, and IO-202, a first-in-class antibody targeting LILRB4 (also known as ILT3), in Phase 1b clinical development for the treatment of acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Additional assets in Immune-Onc’s pipeline include IO-312 (a novel bispecific antibody targeting LILRB4 and CD3), IO-106 (first-in-class antagonist antibody targeting LAIR1), and undisclosed immunology and oncology programs. Immune-Onc has established agreements with leading biopharmaceutical companies, including BeiGene, Regeneron and Roche, to support its global product development plans for IO-108 and IO-202. It has received research grants from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and the California Institute for Regenerative Medicine (CIRM) and investment from The Leukemia & Lymphoma Society Therapy Acceleration Program® (LLS TAP®). Headquartered in Palo Alto, California, Immune-Onc has assembled a diverse team with deep expertise in drug development and proven track records of success at leading biopharmaceutical companies. For more information, please visit www.immune-onc.com and follow us on X and LinkedIn. MEDIA CONTACT Tara Cooper The Grace Group tara@gracegroup.us media@immuneonc.com 650-303-7306

▎药明康德内容团队报道2月20日，以明生物（Immune-Onc Therapeutics）宣布与罗氏（Roche）合作开展一项1b/2期临床试验，评估其靶向LILRB2 （ILT4）的潜在“first-in-class"抗体IO-108联合罗氏的抗PD-L1单抗阿替利珠单抗和抗VEGF单克隆抗体贝伐珠单抗，用于局部晚期或转移性和/或不可切除肝细胞癌（HCC）患者的一线治疗。IO-108是一种全人源IgG4单克隆抗体，可以以高亲和力和特异性结合髓系检查点LILRB2（又称ILT4），阻断LILRB2在肿瘤微环境中与癌症免疫抑制相关的配体HLA-G、ANGPTLs、SEMA4A和CD1d的相互作用。阿替利珠单抗联合贝伐珠单抗是美国FDA批准的肝细胞癌一线免疫联合疗法，也是美国国立综合癌症网络（NCCN）推荐的标准治疗方案。根据以明生物新闻稿介绍，IO-108美国1期剂量递增研究数据在2023年美国癌症研究协会（AACR）年会上发表，显示其在多种肿瘤类型中具有良好的安全性，使用IO-108单药治疗或与抗PD-1抗体联用展现出积极的临床获益。IO-108单药治疗和与抗PD-1抗体（帕博利珠单抗、西米普利单抗或替雷利珠单抗）联用正在多个成人癌症患者的扩展队列中进行研究。本次以明生物与罗氏合作开展的是一项全球随机1b/2期临床试验，是罗氏Morpheus-Liver项目的一部分。该试验将评估IO-108联合阿替利珠单抗和贝伐珠单抗（“三联疗法”）对比阿替利珠单抗和贝伐珠单抗标准疗法（“二联疗法”）在既往未接受过全身治疗的局部晚期或转移性和/或不可切除的肝癌患者中的疗效。试验初期将在全球25个中心招募40名肝癌患者接受IO-108三联疗法，并与二联疗法对照组随机对比。主要终点为客观缓解率，关键次要终点包括无进展生存期和总生存期。根据临床合作协议条款，罗氏负责这项临床试验的运作，以明生物将提供支持该试验的IO-108药物并保留IO-108的全球权利。以明生物首席执行官、董事长廖晓伶博士表示：“我们非常高兴与罗氏一起加速推进IO-108的开发。IO-108单药治疗或与T细胞检查点抑制剂联合治疗已在多种实体瘤中显示出临床活性和可接受的安全性。这项合作标志着IO-108作为首选髓系细胞免疫检查点抑制剂与标准免疫疗法用于治疗实体瘤的一个重要里程碑。”参考资料：[1] 以明生物宣布合作开展一项全球随机1b/2期临床试验来评估IO-108用于一线治疗晚期肝细胞癌. Retrieved Feb 21，2024, From https://mp.weixin.qq.com/s/7nXqjgbdpgH6LcCTx8lCBA本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

PALO ALTO, Calif.--( BUSINESS WIRE )--Immune-Onc Therapeutics, Inc. (“Immune-Onc”), a private, clinical-stage biopharmaceutical company dedicated to advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, today announced a Phase 1b/2 clinical trial collaboration with Roche to evaluate Immune-Onc’s IO-108, a first-in-class antibody targeting LILRB2 (also known as ILT4), in combination with Roche’s atezolizumab and bevacizumab for the first-line treatment of patients with locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC). Atezolizumab and bevacizumab is the first cancer immunotherapy combination regimen approved by the U.S. Food and Drug Administration for this setting and is the recommended standard of care by the National Comprehensive Cancer Network. “We are excited to work with Roche to accelerate the development of IO-108,” said Charlene Liao, Ph.D., chief executive officer and board chair of Immune-Onc. “IO-108 has demonstrated clinical activity and an acceptable safety profile across multiple solid tumors as monotherapy and in combination with T cell checkpoint inhibitors. The collaboration marks a significant milestone in establishing IO-108 as the preferred myeloid checkpoint inhibitor for combination with standard of care immunotherapy regimens in solid tumors.” Under the collaboration, Roche will sponsor and conduct the global, randomized Phase 1b/2 trial to evaluate the safety, efficacy and pharmacodynamics of IO-108 in combination with atezolizumab and bevacizumab compared to atezolizumab and bevacizumab, the standard of care treatment regimen for advanced liver cancer. ABOUT THE RANDOMIZED CLINICAL TRIAL The Phase 1b/2 global, randomized HCC study is part of Roche’s Morpheus-Liver program. It will evaluate IO-108 in combination with atezolizumab and bevacizumab (“triplet”) versus atezolizumab and bevacizumab (“doublet”), the standard of care in patients with locally advanced or metastatic and/or unresectable HCC with no prior systemic treatment. Initially, 40 patients will be enrolled across 25 sites worldwide in the IO-108 triplet combination, which will be compared to an active control arm of the atezolizumab and bevacizumab doublet combination. The study’s primary endpoint is objective response rate, and key secondary endpoints include progression-free survival and overall survival. Under the terms of the clinical collaboration agreement, Roche will manage the study operations, and Immune-Onc will supply IO-108 to support the trial while retaining global rights to IO-108. Tecentriq® (atezolizumab) and Avastin® (bevacizumab) are registered trademarks of Genentech, a member of the Roche Group. Learn more about the trial here . ABOUT HEPATOCELLULAR CARCINOMA According to the American Cancer Society 1 , more than 800,000 people are diagnosed with liver cancer each year worldwide. It is also one of the leading causes of cancer deaths worldwide, accounting for more than 700,000 deaths each year. The number of people diagnosed is predicted to rise, with the incidence of liver cancer increasing by 55.0% and the number of deaths increasing by 56.4% between 2020 and 2040 2 . Hepatocellular carcinoma is the most common form of liver cancer in the United States, making up almost 90% of cases 3 . Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD), and cirrhosis resulting from these conditions 4 . ABOUT IO-108 IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards the myeloid checkpoint, LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A, and CD1d. Clinical data from the U.S. Phase 1 dose escalation study of IO-108 ( NCT05054348 ) was presented at the 2023 American Association for Cancer Research annual meeting and demonstrated a favorable safety profile and encouraging clinical benefit utilizing IO-108 as a monotherapy and in combination with anti-PD-1 across multiple tumor types. IO-108 is being studied in several expansion cohorts in adult cancer patients as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab). A global, randomized Phase 1b/2 study is underway to evaluate IO-108 in combination with atezolizumab and bevacizumab as a potential first-line therapy for hepatocellular carcinoma (HCC). ABOUT IMMUNE-ONC THERAPEUTICS, INC. Immune-Onc Therapeutics Inc. (“Immune-Onc”) is a private, clinical-stage biopharmaceutical company dedicated to discovering and developing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors. Immune-Onc has a differentiated pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB). Immune-Onc’s focused platform approach has led to the development of several promising therapeutics across various stages of development. Those include IO-108, an antagonist antibody targeting LILRB2 (also known as ILT4), in Phase 1b/2 clinical development for solid tumors, and IO-202, a first-in-class antagonist antibody targeting LILRB4 (also known as ILT3), in Phase 1b clinical development for the treatment of acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). IO-202 has the potential to be the best-in-class antibody therapy for lupus and can extend to other indications in immunology and inflammation. Additional assets in Immune-Onc’s pipeline include IO-312 (a novel bispecific antibody targeting LILRB4 and CD3), IO-106 (first-in-class antagonist antibody targeting LAIR1), and undisclosed immunology and oncology programs. Immune-Onc has established agreements with leading biopharmaceutical companies, including BeiGene , Regeneron and Roche, to support its global product development plans for IO-108 and IO-202. It has received research grants from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and the California Institute for Regenerative Medicine (CIRM) and investment from The Leukemia & Lymphoma Society Therapy Acceleration Program® (LLS TAP®). Headquartered in Palo Alto, California, Immune-Onc has assembled a diverse team with deep expertise in drug development and proven track records of success at leading biopharmaceutical companies. For more information, please visit www.immune-onc.com and follow us on X and LinkedIn . American Cancer Society. About Liver Cancer. Accessed Dec. 7, 2023 at https://www.cancer.org/content/dam/CRC/PDF/Public/8698.00.pdf The latest global burden of liver cancer: A past and present threat. Clin Mol Hepatol. 2023 Apr; 29(2): 355–357. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:6. doi.org/10.1038/s41572-020-00240-3 Epidemiology of non-alcoholic fatty liver disease and hepatocellular carcinoma. JHEP Rep. 2021 Aug; 3(4): 100305. doi: 10.1016/j.jhepr.2021.100305