Benzinga | Jul 7, 2021 07:06AM EDT

NGM Bio Announces Initiation Of Phase 1/2 Clinical Study Of NGM707 For Treatment Of Advanced Solid Tumors

--NGM707, a ILT2/ILT4 dual antagonistic antibody, is engineered to reverse myeloid suppression with the goal of improving patient immune responses to tumors--



--Study to evaluate potential of NGM707 in patients with tumor types with elevated expression of ILT2 and ILT4 as a monotherapy and in combination with KEYTRUDA(r) (pembrolizumab)--

--Approximately 180 patients expected to be enrolled in the Phase 1/2 Study--

SOUTH SAN FRANCISCO, Calif., July 07, 2021 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM) (NASDAQ:NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, announced it has dosed the first patient in a Phase 1/2 study to evaluate the efficacy, safety and pharmacokinetics/pharmacodynamics of NGM707 when given alone or in combination with KEYTRUDA(r) (pembrolizumab), an anti- PD-1 antibody. NGM707 is a novel dual antagonist antibody that inhibits the Immunoglobulin-like Transcript 2 (ILT2) and Immunoglobulin-like Transcript 4 (ILT4) receptors. NGM707 originated from NGM's in-house discovery engine. The program follows NGM120, a glial cell-derived neurotrophic factor alpha-like (GFRAL) antagonistic antibody, which is currently in a Phase 2 study in patients with metastatic pancreatic cancer, as the second NGM wholly owned oncology candidate in the clinic.

"NGM707 is designed to improve tumor responses in cancer patients by both reprogramming immuno-suppressive myeloid cells through ILT4 inhibition and by further stimulating the activity of myeloid and lymphoid cells through ILT2 inhibition. As ILT4 inhibition continues to gain interest as a potentially important oncology strategy, our research suggests that NGM707's novel dual blockade of ILT4 and ILT2 may yield enhanced anti-tumor activity," said Alex DePaoli, M.D., Senior Vice President, Chief Translational Officer at NGM. "As a result, we believe NGM707 offers a potentially compelling treatment profile and could represent an important therapeutic advancement for patients with cancer."

ILT2 and ILT4 are receptors overexpressed on myeloid cells in the tumor microenvironment. These receptors are implicated in suppressing anti-tumor immune responses and may represent myeloid checkpoints that enable certain tumors to evade immune detection. NGM707 was designed with the goal of improving 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 natural killer (NK) and CD8+ T-cell killing of tumor cells and activates macrophage phagocytosis of tumor cells. Furthermore, preclinical studies of NGM707 have shown that the dual blockade of ILT2 and ILT4 may be more effective than blockade of either receptor alone in reversing suppression of Fc receptor signaling. In addition, preclinical work has shown that NGM707 in combination with pembrolizumab acts additively to increase T-cell activation and cytokine secretion.

"As we continue to look for novel agents applicable to a broad range of solid tumors and approaches with stronger anti-tumor immune responses, a therapeutic that addresses key myeloid checkpoint resistance mechanisms could represent a significant advancement for cancer patients," said Patricia LoRusso, DO, Professor of Medicine (Medical Oncology); Associate Cancer Center Director, Experimental Therapeutics, Yale University. "NGM707, by reversing myeloid and lymphoid checkpoints, is a promising approach that can potentially help these patients. We look forward to enrolling patients in this Phase 1/2 study and understanding how NGM707's preclinical benefits may translate to patients in the clinical setting."