The Role of Myeloid Cells in Cancer and Autoimmune Disease

Myeloid cells are abundant and have crucial regulatory functions in a broad range of conditions ranging from cancer to autoimmune diseases. Dysregulation of these myeloid cells causes either suppressed or enhanced immune responses, leading to cancers or autoimmune diseases, respectively.

Image: MDS UK Patient Support Group

Immune-Onc Pipeline

 

Immune-Onc’s research and development programs target myeloid cell surface proteins including the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB). The company brings significant drug discovery and development expertise to this mission, complementary to over a decade of research by academic collaborators, to evaluate the role of these proteins in cancer and autoimmune diseases.

Among these, we currently focus on LILRB4 (also known as ILT3), LILRB2 (also known as ILT4), and LAIR1.

LILRB Family

Our Approach

Equipped with unique expertise in myeloid cell biology and insights into innate immune system dynamics that allow diseased cells to grow and spread in the body, Immune-Onc is developing a novel class of antibodies that modulate or deplete specific subsets of myeloid cells involved in disease pathogenesis. The company’s current pipeline targets the LILRB family of immune inhibitory receptors to reverse immune suppression in solid tumors and to eradicate pathogenic or malignant myeloid cells in autoimmune diseases and blood cancers, repectively.

Blood Cancer Programs

*LLS Therapy Acceleration Program (TAP) investment

**National Cancer Institute (NCI) and California Institute of Regenerative Medicine (CIRM) Grants

  • LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on antigen presenting cells (APCs). LILRB4 is expressed on certain hematologic cancer cells and on certain pathogenic cells involved in autoimmunity and inflammatory processes.

  • IO-202 has completed the dose escalation part of the first-in-human, multicenter, open-label Phase 1 study in the US and the data was presented at European Hematology Association (EHA) Congress in 2023. This Phase 1 trial is currently enrolling patients with newly diagnosed chronic myelomonocytic leukemia (CMML) patients who have not received any hypomethylating agents (HMA), studying IO-202 in combination with azacitidine (NCT04372433).

    The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020, Fast Track designation for relapsed or refractory AML in 2022, Fast Track designation for relapsed or refractory CMML in 2023, and Orphan Drug designation for treatment of CMML in 2024.

  • Engineered and optimized using a proprietary bispecific antibody platform, IO-312 is a first-in-class LILRB4-directed bispecific monoclonal antibody with potential against AML and other hematologic malignancies. Preclinical data presented at the 2023 American Association for Cancer Research Annual Meeting demonstrate that IO-312 led to potent and specific killing of monocytic AML cells in vitro and in vivo. Additional design features include high affinity and specific binding to LILRB4 as well as low affinity binding to CD3 to maximize anti-tumor effect without cytokine release-related toxicities, excellent biophysical properties for efficient manufacturing, and cross-reactivity to non-human primate LILRB4 and CD3 to enable preclinical toxicology assessment for rapid advancement to the clinic.

Immunology and Inflammation Programs

  • LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on antigen presenting cells (APCs). LILRB4 is expressed on certain hematologic cancer cells and on certain pathogenic cells involved in autoimmunity and inflammatory processes.

Solid Tumor Programs

*Roche leads

**Immune-Onc leads

  • LILRB2, also known as ILT4, is expressed mostly by myeloid cells, including monocytes, dendritic cells, macrophages, and neutrophils. In solid tumors, interaction of LILRB2 with tumor microenvironment (TME) relevant ligands, including HLA-G, ANGPTLs, SEMA4A, and CD1d, induces a tolerogenic phenotype in myeloid cells, thereby suppressing T cell activation and promoting tumor immune evasion.

  • 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 that are 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.

    Immune-Onc has established agreements with leading biopharmaceutical companies, including BeiGene and Regeneron, to support its global product development plans for IO-108. A Roche-led, 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) (NCT04524871).