NGM Bio Announces Clinical Trial Collaboration With Merck Related to Ongoing Phase 1/2 Trial of an ILT2/ILT4 Dual Antagonist Antibody in Combination With Merck’s KEYTRUDA

NGM Biopharmaceuticals, Inc. recently announced a clinical trial collaboration and supply agreement with Merck 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, MD, Chief Medical Officer at NGM Bio. “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.

The Phase 1 portion (n≅60) of the trial includes a monotherapy dose escalation arm (Part 1a) and a dose-finding arm in combination with KEYTRUDA (pembrolizumab) (Part 1b). The Phase 2 portion (n≅120) of the trial will employ a basket design that will include expansion cohorts of patients treated with NGM707 monotherapy (Part 2a) or NGM707 in combination with KEYTRUDA (Part 2b) in a variety of selected solid tumor types.

For additional information about the trial, including types of cancers being evaluated and other eligibility criteria, please click here to visit the listing on clinicaltrials.gov.

NGM’s currently disclosed oncology product candidates are all derived from the company’s in-house discovery engine and are wholly owned by NGM. These oncology programs include: NGM120, a GFRAL antagonist antibody in a Phase 2 trial for the treatment of metastatic pancreatic cancer; NGM707, an ILT2/ILT4 (LILRB1/LILRB2) dual antagonist antibody in a Phase 1/2 trial for the treatment of advanced solid tumors; NGM831, an ILT3 (LILRB4) antagonist antibody, planned to enter into a Phase 1 trial in advanced solid tumors in the first half of 2022; and NGM438, a LAIR1 antagonist antibody, also planned to enter into a Phase 1 trial in advanced solid tumors in the first half of 2022.

NGM is a biopharmaceutical company focused on discovering and developing novel therapeutics based on scientific understanding of key biological pathways underlying retinal diseases, cancer and liver and metabolic diseases. 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. All of our therapeutic candidates have been generated by our in-house discovery engine; today, we have seven disclosed programs, including four in Phase 2 or 2b studies, across three therapeutic areas. For more information, visit www.ngmbio.com.