NGM Biopharmaceuticals, Inc., a biotechnology company focused on discovering and developing transformative therapeutics for patients, announced a clinical trial collaboration and supply agreement with Merck (known as MSD outside of the United States and Canada) to evaluate NGM707, NGM’s wholly-owned novel ILT2/ILT4 dual antagonist antibody, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA. NGM is currently enrolling patients in the Phase 1/2 trial, initiated in June 2021, to evaluate the potential of NGM707 as a monotherapy and in combination with KEYTRUDA in adult patients with advanced or metastatic solid tumors with elevated expression of ILT2 and ILT4.

“ILT2 and ILT4 are among a group of myeloid immune checkpoint receptors that are upregulated in patients who do not respond to T-cell checkpoint therapy, suggesting that they are potential resistance mechanisms that generate an immunosuppressive state in the tumor microenvironment. We’re excited by the unique profile of NGM707 in the myeloid checkpoint inhibition space. Our preclinical studies suggest that NGM707’s dual blockade of ILT2 and ILT4 may be more effective than blockade of either receptor alone in reversing myeloid based immune suppression, which is known to limit anti-tumor immunity,” said Hsiao D. Lieu, M.D., Chief Medical Officer at NGM Bio.

Dr. Lieu continued, “We’re pleased to enter into this agreement with Merck for our ongoing Phase 1/2 trial of NGM707. In preclinical models, we have demonstrated that NGM707 in combination with KEYTRUDA acts additively to increase T cell activation and cytokine secretion. We look forward to evaluating how these mechanisms of action translate in the clinic to potentially enable broader and deeper anti-tumor immune responses, bringing the promise of immunotherapy to more cancer patients.”

ILT2 and ILT4, inhibitory receptors with enriched expression on myeloid cells in the tumor microenvironment, are myeloid checkpoints that may enable certain tumors to evade immune detection, thereby suppressing patients’ anti-tumor response. NGM707 is being developed with the goal of improving patient immune response to tumors by inhibiting both ILT2 and ILT4. By inhibiting both ILT2 and ILT4, NGM707 may be able to overcome the potential redundant role the two receptors play when co-expressed in myeloid cells and reprogram those cells to enhance T cell activity and proliferation. In addition, ILT2 blockade may drive further benefit through reducing suppression in certain lymphoid cells capable of directly attacking tumor cells.