NGM Expands Oncology Portfolio With First Immuno-Oncology Development Candidate

NGM Biopharmaceuticals, Inc. recently announced the expansion of its oncology portfolio with its first immuno-oncology development candidate, NGM707, a novel dual antagonist antibody that inhibits Immunoglobulin-like transcript 2 (ILT2) and Immunoglobulin-like transcript 4 (ILT4). NGM707 joins NGM120, a first-in-class antagonistic antibody that binds glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) and inhibits growth differentiation factor 15 (GDF15) signaling, in NGM’s oncology portfolio. NGM120 is in an ongoing Phase 1a/1b trial in patients with cancer and cancer anorexia/cachexia syndrome (CACS).

ILT2 and ILT4 receptors expressed on myeloid cells in the tumor microenvironment are implicated in suppressing anti-tumor immune responses and may represent checkpoints that enable tumors to evade immune detection. Suppressive myeloid cells enriched with ILT2 and ILT4 receptors are upregulated in certain cancer types, while ILT2 is also expressed on natural killer (NK) cells, B cells and a subset of highly cytolytic T cells. Of note, ILT2 and ILT4 are upregulated on macrophages in the tumor microenvironment of certain cancer patients that are non-responders to T cell checkpoint inhibitor therapy and, therefore, may serve as T cell checkpoint inhibitor resistance mechanisms. Reversing myeloid suppression, or myeloid reprogramming, represents a promising new therapeutic area of immuno-oncology.

NGM scientists have spent several years researching members of the leukocyte Ig-like receptor (LILR) family of immunosuppressive receptors, including ILT2 and ILT4. NGM707 is designed to attempt to improve patient immune responses to tumors by inhibiting both the ILT2 and ILT4 receptors. In preclinical studies of NGM707, NGM has demonstrated that blockade of ILT4 reverses myeloid cell immune suppression, while blockade of ILT2 promotes NK and CD8⁺ T cell killing of tumor cells and activates macrophage phagocytosis of tumor cells. In addition, preclinical studies of NGM707 have shown that the dual blockade of ILT2 and ILT4 acts synergistically to reverse suppression of Fc receptor signaling.

“NGM707 represents another example of NGM’s core strength in deeply interrogating human biology, identifying the most promising targets and engineering tailored biologics to advance potentially transformative medicines for patients,” said David J. Woodhouse, PhD, Chief Executive Officer at NGM. “As ILT4 inhibition continues to gain interest as a potentially important anti-tumor strategy, our research suggests that NGM707’s novel dual blockade of ILT4 and ILT2 may yield enhanced anti-tumor advantages. We look forward to advancing NGM707 into the clinic next year and providing further updates on our myeloid reprogramming strategy.”

NGM707 was discovered by NGM under its strategic collaboration with Merck.

Dr. Woodhouse commented, “Merck recently presented encouraging findings from an early clinical trial evaluating its investigational anti-ILT4 therapeutic candidate, MK-4830. We are working closely with Merck, given their expertise in immuno-oncology, to determine how to best apply NGM707’s dual anti-ILT2/anti-ILT4 mechanism, enrich our mutual understanding of stromal biology and maximize the potential of myeloid checkpoint inhibition, with the goal of extending the benefits of immunotherapy to as many cancer patients as possible.”

NGM is a biopharmaceutical company focused on discovering and developing novel therapeutics based on scientific understanding of key biological pathways underlying liver and metabolic diseases, retinal and inflammatory diseases and cancer. We leverage our biology-centric drug discovery approach to uncover novel mechanisms of action and generate proprietary insights that enable us to move rapidly into proof-of-concept studies and deliver potential first-in-class medicines to patients. At NGM, we aspire to operate one of the most productive research and development engines in the biopharmaceutical industry, with multiple programs in clinical development. For more information, visit www.ngmbio.com.