IL18RAP

IL-18 modulation has potential for broad applicability in multiple inflammatory diseases Phase 2-ready program complementary to Evommune's immunology pipeline Phase 1 trial demonstrated good safety and tolerability, favorable pharmacokinetics and target engagement PALO ALTO, Calf., June 24, 2024 /PRNewswire/ -- Evommune, Inc., a clinical stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases, today announced it has entered into a definitive, worldwide license agreement with AprilBio Co., Ltd. (Kosdaq: 397030), a biopharmaceutical company based in South Korea dedicated to developing specialized biologics and antibody drugs, for an IL-18 targeted fusion protein. Under the terms of the agreement, Evommune receives exclusive, worldwide rights to research, develop and commercialize APB-R3, to now be known as EVO301, a long-acting injectable fusion protein that is designed to neutralize the signal pathway of IL-18 for the regulation of inflammation. Evommune plans to initiate a Phase 2 clinical trial in early 2025. "We are committed to making a difference for patients suffering from chronic inflammation. Adding this exciting new targeted molecule is another important growth step for Evommune. EVO301 is a product candidate leveraging a novel approach in a mechanism that has demonstrated activity in prior clinical trials. While we continue to execute on our pipeline, including EVO756, our MRGPRX2 antagonist, EVO301 provides the potential to offer a best-in-class therapeutic for patients being underserved by existing treatment options in multiple diseases. We believe the proprietary serum albumin binding motif fused to an IL-18 binding protein may facilitate deep tissue penetration with an extended half-life," said Luis Pena, Evommune President & CEO. "As we evaluate partners of our pipeline products, we are thrilled to license the IL-18 fusion protein to Evommune, a company with significant drug development expertise in the areas of chronic inflammatory diseases. Evommune's ability to broadly develop this product candidate throughout its potentially broad life cycle process was a key driver of our desire to collaborate with them," commented Dr. Sang-hoon Cha, CEO at AprilBio. About EVO301 A long-acting injectable therapeutic, EVO-301 is a fusion-protein that is designed to neutralize the signal pathway of IL-18 for the regulation of inflammation. IL-18, a proinflammatory cytokine of the IL-1 family, plays an important role in the T-cell-helper type 1 inflammatory response, primarily by its ability to induce IFN-gamma production in T-cells and natural killer cells. About AprilBio AprilBio Co., Ltd. is a biopharmaceutical company in South Korea founded in 2013. The company is specialized in development of specialized biologics and antibody drugs. The company's platform technologies include a human phage-display Ab library and Anti-Serum Albumin Fab-Associated (SAFA) technology (versatile building block for half-life extension and generation of novel biological therapeutics). AprilBio is focused on rare diseases, oncology, autoimmune and inflammatory diseases. About Evommune, Inc. Evommune, Inc., a Palo Alto based biotech company, is creating game-changing science to treat immune-mediated inflammatory diseases by discovering, developing, and delivering therapies that address symptoms and halt progressive disease. For more information, please visit Evommune.com.

引言基于自然杀伤(NK)细胞的免疫疗法有望治疗癌症；然而，它的效力仍然有限，因此有必要制定替代战略。2024年5月21日，中国科学技术大学倪芳、郑昌成及魏海明共同通讯在Cell Reports Medicine在线发表题为“Venetoclax acts as an immunometabolic modulator to potentiate adoptive NK cell immunotherapy against leukemia”的研究论文，该研究表明，venetoclax，一种FDA批准的BCL-2抑制剂，在体外和体内直接激活NK细胞，增强其对急性髓性白血病(AML)的细胞毒性，可能独立于BCL-2抑制。该研究通过大量和单细胞RNA测序、亲和度测量和功能分析等综合方法，证明venetoclax增加NK细胞对AML细胞的亲和度，并在免疫突触(IS)形成过程中促进溶解颗粒极化。值得注意的是，研究发现了一个独特的CD161lowCD218b+ NK细胞亚群，对venetoclax治疗表现出显著的敏感性。此外，venetoclax通过NF-κB途径促进线粒体呼吸和ATP合成，从而促进NK细胞中IS的形成。基于细胞的抗癌免疫疗法已经彻底改变了癌症治疗。不同类型的免疫细胞，特别是那些通过直接接触或释放细胞毒性分子破坏靶细胞的免疫细胞，已被用于这一目的。自然杀伤(NK)细胞是细胞毒性先天淋巴样细胞，保护宿主免受病毒感染和癌症。与T细胞不同，NK细胞可以自发地检测和消除感染和恶性细胞，而无需事先特异性激活。同种异体NK细胞特别适合用于过继性转移，因为它们可以减轻细胞因子释放综合征发生的风险。NK细胞的这些特性使得它们在基于细胞的癌症免疫治疗中具有很高的吸引力。NK免疫疗法作为一种可行有效的治疗方法，在临床前和早期临床研究中显示出巨大的前景。然而，基于NK细胞的癌症免疫治疗面临着重大挑战，主要集中在优化NK细胞来源，增强其功能能力和体内长期持久性。正在作出广泛的努力来克服这些障碍，并最大限度地发挥NK细胞的治疗潜力。治疗性NK细胞的多种来源已被探索，包括单倍体、脐带血、干细胞衍生、适应性、细胞因子诱导的记忆样、嵌合抗原受体和NK细胞系。基于细胞因子的药物、接合分子和免疫检查点抑制剂已被用于增强NK细胞的功能。尽管研究NK细胞免疫疗法的临床前和临床试验取得了相当大的进展，但其在癌症治疗中的疗效仍然有限。因此，迫切需要探索能够增强NK细胞免疫治疗并提高其治疗癌症疗效的策略。模式图（Credit: Cell Reports Medicine）Venetoclax是FDA批准的BCL-2小分子抑制剂，BCL-2是一种关键的抗凋亡蛋白，在肿瘤发生、肿瘤存活、淋巴细胞发育和免疫系统调节中起着至关重要的作用。它适用于患有慢性淋巴细胞白血病/小淋巴细胞白血病的成人患者，也可用于75岁以上的急性髓系淋巴瘤（AML）成人患者或患有阻止强化诱导化疗的疾病的患者，也可与低甲基化剂或低剂量阿糖胞苷联合使用。尽管venetoclax具有公认的凋亡作用，但其对抗肿瘤免疫反应的广泛影响在很大程度上仍未被探索。该研究提出了一种潜在可行的方法来增强NK细胞免疫疗法。通过确定venetoclax增强NK细胞功能的潜力，包括促进线粒体代谢、IS形成和细胞毒性，发现了一种改善癌症治疗结果的有希望的策略。总的来说，该研究结果表明venetoclax是NK细胞功能的多方面免疫代谢调节剂，并为增强NK细胞为基础的癌症免疫治疗提供了一个有希望的策略。原文链接https://doi.org/10.1016/j.xcrm.2024.101580责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

OSE’s Tedopi is a neoepitope-based immunotherapy activating tumour-specific T-cell cancer vaccine. Image Credit: Gorodenkoff / Shutterstock. The French company OSE Immunotherapeutics has provided an update for its clinical pipeline, with plans to start a confirmatory Phase III study for its cancer vaccineTedopi in the US in Q2 2024. The company has received positive recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based on the positive data from the Phase III trial (NCT02654587) evaluating Tedopi as a second or third-line therapy in patients with advanced non-small cell lung cancer patients following treatment failure with immune checkpoint inhibitors (ICI). Additionally, OSE is seeking approval from the FDA to validate the companion diagnostic test for Tedopi, developed by Genome Diagnostics. Tedopi is a neoepitope-based immunotherapy activating tumour-specific T-cell cancer vaccine. Apart from the Phase III trial, OSE is also conducting three Phase II trials evaluating Tedopi as a combination therapy in solid tumours such as pancreatic, ovarian and lung cancers. The results from the Phase II trial of Tedopi in combination with chemotherapy in pancreatic cancer patients are expected this year. Data from the Phase II trials (NCT04713514 and NCT03806309) for Tedopi in combination with MSD’s Keytruda (pembrolizumab) and Bristol Myers Squibb ’s Opdivo (nivolumab), respectively, is expected in 2025. OSE’s ulcerative colitis therapy lusvertikimab (OSE-127) is being investigated in a Phase II placebo-controlled trial (NCT04882007). The recruitment for the trial is expected to be completed in Q1 of this year, with initial results expected by mid-2024, as per a 19 January press release. The interleukin (IL)-7 receptor antagonist is also being evaluated in preclinical studies as a treatment for acute lymphoblastic leukaemia (ALL). In July 2023, OSE received a positive opinion on Orphan Drug Designation for lusvertikimab for the treatment of ALL by the EMA. OSE-279 is a programmed cell death 1 (PD-1) inhibiting monoclonal antibody. It is being evaluated as a treatment for solid tumours or lymphomas in a dose-finding and expansion Phase I trial (NCT05751798). OSE is also developing two monoclonal antibodies against signal regulatory protein α (SIRPα), BI 765063/ OSE-172 and BI 770371, in collaboration with Boehringer Ingelheim. BI 765063 is being evaluated as a combination therapy with different cancer therapies such as Boehringer’s ezabenlimab, BI 836880, chemotherapy and Eli Lilly’s Erbitux (cetuximab) in a Phase I trial (NCT05249426). BI 770371 is being evaluated as a monotherapy and in combination with a PD1 inhibitor, BI 754091, in an international Phase I dose escalation and expansion trial (NCT05327946) in patients with solid tumours. OSE is advancing the anti-CD28 selective monoclonal antibody FR104/VEL-101 in partnership with Denmark-based Veloxis Pharmaceuticals. It is researched as a treatment to help prevent organ rejection in people who have had a kidney transplant. In February 2022, the therapy received a fast track designation by the FDA for prophylaxis against transplant rejection. Veloxis is planning Phase II trials for the subcutaneous therapy.