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6月3日，Biolojic Design宣布与默克达成多靶点药物发现合作。默克将利用Biolojic Design的AI驱动发现平台开发best-in-class多抗，合作聚焦免疫学和肿瘤学，包括针对新治疗靶点的ADC。 Biolojic Design将获得预付款和研究资金，并有资格获得药物发现、开发、监管和商业里程款，总额可能高达3.46亿欧元（约合3.76亿美元）。Biolojic Design还将有资格获得产品净销售额的分级特许权使用费。 Biolojic Design总部位于以色列，是一家利用计算生物学和AI，将抗体转化为可编程智能药物的公司。该公司的平台可以生成多特异性抗体，作为执行“和”或“异”（“and”or“xor”）功能的逻辑门。 Biolojic Design的产品管线专注于自身免疫性疾病和免疫肿瘤学，其平台开发出了第一个进入临床的AI设计的抗体（AU007），目前正处于II期临床试验阶段。此外，Biolojic Design还有四款产品处于临床前阶段。 Biolojic Design管线（来源：Biolojic Design官网） 近年来，默克在AI制药领域的合作不断。今年4月，默克宣布与Caris Discovery合作，加速新型ADC药物开发。去年9月，默克分别与AI制药明星公司BenevolentAI、Exscientia签署了两项针对小分子候选药物的AI发现协议；同月，默克还宣布扩大了与Quris-AI的协议，使用该公司的AI平台来检查候选药物的肝毒性风险。 参考资料： https://www.globenewswire.com/news-release/2024/06/03/2892401/0/en/Biolojic-Design-Enters-into-a-Multi-Target-Drug-Discovery-Collaboration-with-Merck-KGaA-Darmstadt-Germany.html 推荐阅读 专访蔡磊&李龙承：攻克渐冻症，RNAi疗法是“绝望中的希望之光” Nature：一篇「核药」重磅论文 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

Preliminary results show durable anti-tumor activity in multiple solid tumor types among heavily pre-treated patients, including patients whose tumors have progressed through checkpoint inhibitors The results confirm the ability of AU-007, a human IgG1 monoclonal antibody designed using artificial intelligence, to harness the power of interleukin-2 (IL-2) to reduce solid tumors, and support ongoing and planned Phase 2 expansion cohorts in combination with low-dose aldesleukin in melanoma, renal cell carcinoma and non-small cell lung cancer LARKSPUR, Calif.--(BUSINESS WIRE)-- Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, today shared interim results from its Phase 1/2 trial of AU-007, the first human monoclonal antibody designed using artificial intelligence to be tested in a clinical trial. The data will be presented in a poster session at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago, Illinois. “The level and scope of anti-tumor activity we’re seeing across solid tumor types are remarkable so early in clinical development, particularly the partial responses and metabolic complete response. The durability of the tumor reductions seen in several patients suggests the formation of immune memory of the cancerous cells. These results validate our long-held belief that AU-007 could widen the therapeutic window of IL-2 by redirecting IL-2 toward CD8+ T and natural killer cells that can kill tumor cells and away from immunosuppressive regulatory T cells and the vasculature,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “While other developmental IL-2 therapies focus on changing IL-2 itself, AU-007 is a human antibody that is a well-established therapeutic modality. This provides sources of advantage and differentiation. As we treat patients in earlier lines of therapy, we are confident AU-007 is emerging as a potential best-in-class regimen.” Key findings from the updated results of the AU-007 Phase 1/ 2 study, with data available on 59 patients as of the data cutoff date of April 9, 2024, are as follows. Well-tolerated safety profile: No evidence of vascular leak syndrome or pulmonary edema reported at all dose levels evaluated. All drug-related adverse events were Grade 1 or 2 except for: One patient with Grade 4 CRS that resolved quickly with steroids. This patient was noted retrospectively to have subclinical elevated IL-6 serum levels at baseline. Five patients experienced transient (3-7 days) Grade 3 or 4 lymphopenias that were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue. One patient with Grade 3 anemia who entered the study with Grade 2 anemia. Profound and durable tumor shrinkage observed in multiple tumor types: A patient with large-volume metastatic melanoma whose tumors had progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (9 mg/kg) and one 135K IU/kg low dose of IL-2 and experienced 76% shrinkage (unconfirmed partial response) in target lesions at 8 weeks. Another patient with metastatic melanoma whose tumors had also progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (4.5 mg/kg) and one 15K IU/kg low dose of IL-2 and achieved 48% shrinkage in target lesions. A patient with head and neck cancer whose tumors had progressed through an anti-PD-1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and 45K IU/kg IL-2 dose every two weeks and experienced 32% shrinkage (confirmed partial response) in a cervical bone metastasis, as well as reduced pain and improved motor function in an affected hand. A patient with bladder cancer whose tumors had progressed through an anti-PD-L1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and one 45K IU/kg IL-2 dose and achieved a durable metabolic complete response. Additional tumor shrinkages were observed in patients with widespread large-volume disease in renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and MSI-stable (MSS) colorectal cancer. Unique pharmacodynamic (PD) and pharmacokinetic (PK) profiles in the IL-2 class: Decreases in peripheral regulatory T cells (Tregs) and increases in CD8/Treg ratios demonstrate AU-007’s ability to redirect IL-2 and prevent the negative feedback loop to Tregs. AU-007 and low-dose aldesleukin also substantially increases peripheral natural killer (NK) cells. AU-007 PK demonstrates dose-proportionality over the dose range tested and no signs of neutralizing anti-drug antibodies (ADAs) activity, and a half life of 15+ days. The Phase 2 expansion cohorts of the AU-007 study are continuing to enroll patients with a focus on melanoma and RCC. The company anticipates presenting updated clinical data in the second half of 2024. Additional Phase 2 expansion cohorts are planned to evaluate AU-007 and aldesleukin in second-line PD-L1+ NSCLC, with and without the PD-L1 antibody avelumab. The poster, “Updated results of a phase 1/2 study of AU-007, a monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, in patients with advanced solid tumors,” (Abstract 2527) is available to meeting registrants as an electronic poster on the ASCO online meeting platform and will be presented live in the poster session “Developmental Therapeutics—Immunotherapy” on Saturday, June 1, 2024, 9:00 a.m. to 12:00 p.m. CDT. To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit . For patients and health professionals in Australia, please visit . About AU-007 AU-007 is a human IgG1 monoclonal antibody designed using artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy. About Aulos Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ immune systems toward killing tumor cells. Matching world-class machine learning from co-founder Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a computationally designed human antibody that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and Apple Tree Partners (ATP) and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit , X (@AulosBioscience) and LinkedIn.