LILRB1

OMX-0407: clinical-stage, spectrum selective SIK kinase inhibitor with dual effect on tumor growth and immune evasion IOMX-0675: best-in-class antibody targeting immunosuppressive receptors LILRB1 & LILRB2 on immune cells iOTarg screening platform: uncovering novel mechanisms of immune evasion in colorectal cancer MARTINSRIED, Germany and MUNICH, Germany, April 03, 2024 (GLOBE NEWSWIRE) -- iOmx Therapeutics AG (iOmx), a clinical-stage biopharmaceutical company translating unexplored immune evasion biology into a growing pipeline of biomarker-enabled drug programs, today announces that it will present new data on its lead I/O drug candidates OMX-0407 and IOMX-0675, plus its proprietary iOTarg™ screening platform at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024 taking place from April 5-10, 2024, in San Diego, California. "We are excited to share updates on our two lead I/O programs targeting a broad range of solid tumor indications and our high-throughput target screening platform – iOTarg. The data presented will provide insights into the mode of action of our clinical-stage candidate OMX-0407 and for the first time publicly introduce our second lead candidate IOMX-0675, a highly differentiated, best-in-class antibody that impressively re-activates adaptive and innate immunity in the tumor microenvironment,” said Dr. Apollon Papadimitriou, CEO of iOmx Therapeutics. ”Together with the new targets identified by our screening platform, this marks a step forward in our mission to uncover novel immune evasion mechanisms and develop targeted therapies that significantly improve patient outcomes in cancer treatment.” Details of the abstracts and the poster presentations: OMX-0407: spectrum-selective SIK kinase inhibitor with dual effect on tumor growth and immune evasion An in-depth mode of action analysis demonstrated that spectrum selective kinase inhibitor OMX-0407 drives cell-cycle arrest in vitro and in vivo. Through tyrosine kinase signaling, OMX-0407 interferes with cell cycle regulation and cancer cell proliferation. Complementary to this direct mode of action, OMX-0407 also potentiates tumor cell apoptosis in response to death receptor ligands including tumor necrosis factor through salt inducible kinase signaling. With this dual mode of action, OMX-0407 has shown striking single-agent efficacy in multiple pre-clinical tumor models. The spectrum selective SIK kinase inhibitor is currently in Phase I clinical trial. Title: Salt-inducible kinase inhibitor OMX-0407 drives cell-cycle arrest in vitro and in vivo: An in-depth MoA analysis by phospho-proteomics Abstract number: 514/11 Session title: Cell cycle, transcription regulation, and anticancer drug action, Section 21 Date and time: April 7, 2024; 1:30 PM – 5:00 PM PDT IOMX-0675: a best-in-class cross-specific antibody repolarizing the tumor microenvironment IOMX-0675 addresses a key immunoregulatory receptor family expressed on myeloid cells and other immune cells. This receptor superfamily, the leukocyte immunoglobulin-like receptor (LILRs), contains both immune-suppressive and immune-activating receptors, displaying very high structural homology. The antibody IOMX-0675 targets the two most potent immunosuppressive members of this family, namely LILRB1/2. In a dual targeting approach, iOmx has generated a fully human, cross-specific, high-affinity ligand-blocking antibody that simultaneously neutralizes these two key immune-suppressive receptors, while sparing the closely related immune-activating LILR family members, LILRA1 and LILRA3. Dual targeting of these receptors on myeloid cells results in a pronounced anti-tumor immune response, retuning the tumor microenvironment and activating T cells against cancer cells. The specificity and dual approach of IOMX-0675 indicate its potential as a promising candidate to provide a new treatment avenue for patients with limited options due to resistance to current therapies. Title: IOMX-0675, a LILRB1 and LILRB2 cross-specific anybody, effectively repolarizes immunosuppressive myeloid cells and activates T cells leading to potent tumor cell killing Abstract number: 1362 / 13 Session title: Immune Checkpoints and Inhibitory Molecules 1, Section 3 Date and time: April 8, 2024; 9:00 AM – 12:30 PDT iOTarg™ Screening Platform: Uncovering Colorectal Cancer Evasion Mechanisms iOmx's high-throughput iOTarg™ platform reveals novel mechanisms of colorectal cancer evasion of antigen-specific T cell killing. This pioneering research identifies new therapeutic targets, offering prospects for expanding treatment options in immune oncology. Title:iOTarg™ screening platform reveals novel mechanisms of colorectal cancer evasion from antigen-specific tumor cell killing by T cells Abstract number: LB080 / 16 Session title: Immunology 1, Section 54 Date and time: April 7, 2024; 1:30 PM – 5:00 PM PDT About iOmx Therapeutics iOmx Therapeutics ( ) is a clinical-stage company that harnesses deep tumor and myeloid biology insights, along with its proprietary iOTarg™ target screening platform, to generate novel treatments for the most prevalent solid tumor indications. The company is translating unexplored immune evasion biology into a growing pipeline of biomarker-enabled drug programs. Focused on developing drugs with single agent activity, iOmx is creating potential new backbone therapies in a modality-open fashion. By applying its comprehensive drug discovery & development expertise, iOmx is committed to shaping the future of cancer therapy. The company’s lead program OMX-0407, is a proprietary first-in-class spectrum-selective SIK kinase inhibitor, currently being investigated in Phase I clinical trials to treat multiple solid tumors. iOmx is backed by international venture capital investors, such as Athos Biopharma, Sofinnova Partners, Wellington Partners, MIG Capital and M Ventures. iOmx is based in Martinsried/Munich, Germany. Media contact MC Services AG Katja Arnold, Julia von Hummel, Shaun Brown T: +49(0)89 2102280 iomx@mc-services.eu

本文为转化医学网原创，转载请注明出处 作者：Rainbow 导读： 长链非编码RNA（lncRNA）在各种癌症特征的表观遗传调控中发挥关键作用，包括增殖、存活和通过与表观遗传修饰因子、转录因子/共激活因子或核糖核蛋白复合物相互作用的转移。 3月22日，上海交通大学冯海忠、李彦欣和昆明医科大学陈策实共同通讯在期刊《Molecular Cancer 》上在线发表题为“LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling”的研究论文， 研究结果揭示了LINC00115作为乳腺癌干细胞的关键调控因子，并强调了靶向LINC00115和SETDB1作为化疗耐药性乳腺癌的潜在治疗策略。 https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-01975-3 研究背景 01 癌症干细胞是癌细胞中的一个小群体，具有无限的增殖潜能和启动肿瘤克隆的能力。 累积的数据表明，癌症干细胞是各种癌症（包括乳腺癌）中治疗耐药、转移和复发的关键障碍，然而其潜在机制仍然不明确。 LINC00115在包括肺腺癌、视网膜母细胞瘤、前列腺癌、卵巢癌、乳腺癌和胶质瘤在内的多种癌症中上调。LINC00115是这些癌症的预后因子。LINC00115已被确认为功能性miRNA海绵，可调控miR-200s、miR-7和miR-489-3在癌症进展中的作用。已观察到TGF-β的上调介导神经胶质瘤干细胞的干性。研究表明，LINC00115通过上调SOX9并抑制Wnt/β-catenin通路，在卵巢癌干细胞中增强干性并抑制凋亡。 然而，LINC00115在治疗耐药性癌症干细胞中的作用仍未知。 HIF1α是通过促进乳腺癌干细胞表型来增强乳腺癌化疗耐药性和转移的通路的常见成分。HIF1α蛋白的稳定性和活性由一种包括蛋白激酶和蛋白/脂质磷酸酶的信号级联介导。GSK3β在氧依赖降解结构域内磷酸化HIF1α，导致HIF1α通过蛋白酶体途径增加降解。PLK3也可以通过直接与Ser576和Ser657上的HIF1α相互作用来磷酸化HIF1α，导致类似于GSK3β调控的HIF1α不稳定化。 SETDB1是一种H3K9甲基转移酶，负责组蛋白H3上的赖氨酸9甲基化，已被证明可以甲基化几种非组蛋白，如Akt。SETDB1依赖性甲基化在调节增殖、分化和细胞命运以及抑制癌症方面增强或阻碍各自的激酶活性。 目前尚不清楚SETDB1在乳腺癌化疗耐药和转移中对HIF1α信号传导的重要性。 研究发现 02 在这项研究中，研究人员对紫杉醇耐药的乳腺癌干细胞进行了全基因组lncRNA表达分析，并确定LINC00115是一个关键调节因子。结合RNA pull-down和质谱（MS）分析，研究人员展示了LINC00115作为一个支架lncRNA，通过 SETDB1/PLK3/HIF1α 信号传导调控乳腺癌干细胞的干性、化疗耐药性和转移。 研究发现揭示了治疗耐药乳腺癌干细胞的一个新调控因子。 研究结论 03 综上所述， 研究结果揭示了LINC00115作为乳腺癌干细胞的关键调控因子，并强调了靶向LINC00115和SETDB1作为化疗耐药性乳腺癌的潜在治疗策略。 参考资料： https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-01975-3 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。 热门·直播/活动 🕓 线上｜03月28日 ▶Twist全外显子组测序应用新篇章 🕓 上海｜03月28日-30日 ▶2024（第二届）合成生物学与生物医学健康大会参会指南公布！ 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！ 点击对应文字 查看详情

BND-35 Receives IND Clearance, and First in Human Phase 1 Trial is Expected to Begin in April 2024 MISGAV, Israel, March 26, 2024 /PRNewswire/ -- Biond Biologics Ltd., a pioneering clinical-stage biopharmaceutical company, developing innovative immunotherapies for cancer and a transformative platform for the intracellular delivery of biologics, is excited to announce that our BND-35 program has been selected for presentation at the esteemed American Association for Cancer Research (AACR) Annual Meeting, scheduled for April 5 - 10, 2024, in San Diego Convention Center, San Diego, CA, USA. BND-35 is distinguished as a humanized IgG4, ILT3 (LILRB4) antagonist antibody, designed to modulate the tumor microenvironment (TME) from immunosuppressive to pro-inflammatory, thereby counteracting tumor growth. BND-35 phase 1 trial includes a unique clinical design, that will be presented in the ACCR, and is based on Biond's extensive pre-clinical work and the ability of BND-35 to block interactions with the various ligands of ILT3. The presentation, titled "BND-35, a novel anti-ILT3 antibody for remodulation of the tumor microenvironment", will be part of the session on "Immune Targets and Therapies." It is scheduled for Monday, Apr 8th, 2024, at 4:05 PM. The session will highlight Biond Biologics' comprehensive preclinical characterization of BND-35, emphasizing its potential as a transformative treatment for solid tumors. BND-35 Oral Presentation Highlights at 2024 AACR Annual Meeting Biond Biologics' pivotal research on BND-35 demonstrates its specificity in binding ILT3 with high affinity, without affecting other ILT-family receptors. The specific blocking of ILT3's interaction with key ligands significantly enhances the pro-inflammatory activity of myeloid cells and effectively reverses ILT3-mediated immune suppression of T cells. The presentation will detail how BND-35, as a standalone therapy and in combination with anti-PD-1 and anti EGFR agents, has shown promising results in restoring T and NK cell activity and inducing a pro-inflammatory TME in various in vitro, ex vivo, and in vivo models. "ILT3 is a clinically validated target that in the past several years have been the focus of several clinical programs. The findings we're presenting at AACR 2024 represent the unique features of BND-35 and why we believe it has the potential to surpass other ILT3 targeting agents," said Motti Hakim, Ph.D., VP R&D at Biond Biologics. "BND-35's ability to remodel the immunosuppressive environment into a pro-inflammatory one, opens new doors for treating solid tumors and our research in this field brings a significant leap forward in our understanding of immune regulation within the TME," Tsuri Peretz, BND-35 project manager at Biond Biologics, added, "We are eager to share our latest advancements with the scientific community. BND-35's compelling preclinical results pave the way for its upcoming first-in-human clinical trial, marking a pivotal step in our quest to provide innovative solutions for patients with solid tumors." In addition to the spotlight on BND-35, Biond Biologics continues to advance its Immuno-Oncology pipeline, including the pre-clinical-stage BND-67 program, and the innovative INspire platform for intracellular delivery of biologics. The presentation will underscore Biond's commitment to groundbreaking research and development, aiming to unlock new pathways for cancer treatment. About Biond Biologics Biond Biologics is at the forefront of developing cutting-edge therapies targeting novel oncology pathways and enabling the intracellular delivery of biologics. By exploring immunoregulatory pathways and pioneering technological platforms, Biond aims to translate advanced science and innovative thinking into transformative drugs for diseases with significant unmet needs. Biond's programs include BND-22 that was partnered with Sanofi, a multi-cell checkpoint first in class ILT2 blocking antibody, and BND-67, a novel agent developed for attenuating CD28 shedding, overcoming PD-1 blockade resistance; an immune evasion mechanism discovered by Biond's scientists. The company is also developing BND-35 – an ILT3 blocking antibody, that targets suppressive myeloid cells in the tumor microenvironment. In addition to its pipeline of immunotherapy agents, Biond is developing INspire – an innovative technological platform that enables the intracellular delivery of protein therapeutics, such as antibodies, proteins or enzymes, into cells. Using INspire, Biond targets, for example, the RAS-RAF signaling pathway, which is a driver in many cancers. Company contact: Tal Sines VP of Business Development Biond Biologics Ltd. +972-4 884 4337 tal.sines@biondbio.com