SIK1

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

- SIK and cGAS are key autoimmune regulators well suited for Nimbus’ structure-based drug design approach - - Company to present pipeline update at the 42nd Annual J.P. Morgan Healthcare Conference on Monday, January 8, 2024 at 7:30 am PT - BOSTON--(BUSINESS WIRE)--Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, announced the advancement and expansion of its pipeline with the addition of discovery programs targeting innate immunity pathways. These programs, targeting the salt-inducible kinase (SIK) family and cyclic GMP-AMP synthase (cGAS), represent promising opportunities to leverage Nimbus’ industry-leading computational and structure-based drug design expertise to develop highly selective, potent medicines addressing areas of significant unmet need. "Building on the success of our TYK2 program, we are broadening our drug discovery engine to unlock new difficult-to-drug targets with compelling biology,” said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. “SIK and cGAS are critical targets in highly prevalent diseases that are well suited to Nimbus’ structure-based drug design approach. We look forward to advancing our discovery and development programs across oncology, immunology, and metabolism to deliver transformative medicines to patients.” Nimbus is advancing its Phase 1/2 trial (NCT05128487) of NDI-101150, a small molecule inhibitor of hematopoietic progenitor kinase 1 (HPK1), and has reported positive dose escalation data showing potential monotherapy clinical benefit for patients with solid tumors. Furthermore, the company expects to initiate IND-enabling activities this year for its oncology program targeting Werner syndrome helicase (WRN). In collaboration with Eli Lilly and Company, Nimbus continues to progress the development of novel targeted therapies that activate AMPK to potentially treat a broad range of metabolic disorders. Nimbus continues to expand its platform capabilities with ongoing investments in cutting-edge technology for drug discovery. Alongside proprietary computational tools which the company has developed in-house, Nimbus’ platform leverages state-of-the-art technology through collaborations such as its recently announced partnership with Anagenex, a leader in generative AI for drug design. Jeb Keiper, M.S., MBA, Nimbus’ Chief Executive Officer, will provide an overview of the company’s progress and pipeline and anticipated milestones for 2024 and beyond at the 42nd Annual J.P. Morgan Healthcare Conference on Monday, January 8, 2024 at 7:30 am PT. About Nimbus Therapeutics Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a clinical-stage HPK1 inhibitor for the treatment of cancer (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, autoimmune conditions, and metabolic diseases. Nimbus is headquartered in Boston, Mass. To learn more about Nimbus, please visit .

Research shows that some lung cancer cells retain a 'memory' of the healthy cell where they came from -- one that might be exploited to make an emerging type of lung cancer treatment called KRAS inhibition more effective. A new understanding of lung cancer cells' "memories" suggests a new strategy for improving treatment, Memorial Sloan Kettering Cancer Center (MSK) researchers have found. Research from the lab of cancer biologist Tuomas Tammela, MD, PhD shows that some lung cancer cells retain a "memory" of the healthy cell where they came from -- one that might be exploited to make an emerging type of lung cancer treatment called KRAS inhibition more effective. The study looked specifically at lung adenocarcinoma, a type of non-small cell lung cancer that is the most common type of lung cancer in the U.S. and responsible for 7% of all cancer deaths. This cancer is frequently driven by mutations in the KRAS gene. "For a long time, cancer-driving KRAS proteins were considered 'undruggable,'" says study co-first author Zhuxuan "Zoe" Li, a doctoral student in the Tammela Lab at MSK's Sloan Kettering Institute. "Within the last few years, however, the U.S. Food and Drug Administration approved the first KRAS inhibitors, with quite a few more in clinical trials. But they don't work for everyone, and most patients' cancers eventually acquire resistance to the drugs and come back." The team's findings -- co-led by postdoctoral fellow Xueqian Zhuang, PhD -- shed important light on lung cancer cells that linger after treatment with a KRAS inhibitor. Importantly, they suggest that separately targeting these cells alongside treatment with a KRAS inhibitor could help prevent recurrence. The study was recently published in Cancer Discovery, a leading journal for biological insights that have important implications for clinical care. Stem Cells With a Day Job' To understand the MSK discovery and its implications, it's helpful to know a little lung biology. Within the lungs, oxygen is absorbed and carbon dioxide released via air sacs called alveoli. The lining of the alveoli is made of two distinct types of cells -- alveolar type 1 (AT1) and alveolar type 2 (AT2). And while they're similarly named, these two cells couldn't be more different. AT1 cells are long and thin, with a large surface to facilitate gas exchange between the lungs and the bloodstream. AT2 cells, meanwhile, play a caretaking role, secreting compounds that are important for the health and function of the lungs, as well as helping maintain and repair the lungs by dividing to create replacement AT1 cells. "You can think of them as stem cells with a day job," Dr. Tammela says. The big problem comes when lung cancer cells -- which typically develop from AT2 cells -- take on some "remembered" properties of the AT1 cells that AT2 cells differentiate into when they're playing their stem cell role. Scientists call these cancer cells "AT1-like" cells. Eliminating AT1-Like Cells Improves Response to KRAS Inhibition In healthy cells, KRAS plays a key role in regulating cell growth and division. But when the gene becomes mutated, it can lead to runaway cell proliferation. KRAS inhibitors can switch off this explosive growth, greatly diminishing tumors, but they still leave behind pockets of cancer cells that aren't sensitive to the drug, and that also give the cancer a chance to develop new mutations to resist the drugs' effects. The research team painstakingly studied these residual cancer cells to uncover the mechanisms of this resistance using genetically engineered mouse models, mice implanted with patient-derived tumors, and tumor samples from patients. They discovered that the cancer cells that remained after treatment were these AT1-like cells. They also found these cells have the capacity to reignite the cancer's runaway growth. "Importantly, we found that if you get rid of these AT1-like cells, it greatly improves the treatment response to KRAS inhibitors," Dr. Tammela says. Eliminating those cells in experimental models is relatively easy, but doing so in the clinic will require further research. "We actually live in a very exciting time with fantastic pharmacology," Dr. Tammela says. "We can engineer molecules to bind to a certain cell type and kill them -- this is how CAR T cell therapy and antibody drug conjugates work. "Now that we've done these proof-of-concept experiments, the next step would be to find surface proteins that are unique to these AT1-like cells and then develop a therapeutic that can bind to them and kill them," he adds.