Our Journey to Improve Outcomes for Patients with Cancer

Immunotherapies are cancer treatments designed to enable a patient’s immune system to fight cancer. Anti-PD1 and anti-PDL-1 therapies are two types of immunotherapies that are designed to inhibit immune checkpoint pathways and have transformed the cancer treatment landscape for certain types of cancer in the last decade. When “active” these pathways act as “brakes” on antitumor immune responses, enabling tumors to evade detection and destruction by the immune system. T cell checkpoint inhibitors essentially work to “release” the “brakes” by inactivating those pathways. While some patients respond well to these T cell checkpoint inhibitors, many unfortunately do not. Many patients who initially experience a full or partial response with T cell checkpoint inhibitors eventually relapse and their disease progresses.

NGM is advancing NGM707, a novel antagonist antibody inhibiting immunoglobulin-like transcript 2 and 4, or ILT2 and ILT4, with the goal of improving immune responses and helping more patients benefit from immunotherapy.

20–30% Overall Response Rate to PD-1/PD-L1 inhibitors
9.5M cancer-related deaths each year, globally
18M newly diagnosed cases each year, globally

*2018; newly diagnosed cancer cases excludes non-melanoma skin cancer

ILT2 and ILT4’s Role in Suppressing Patients’ Anti-Tumor Immune Response

ILT2 and ILT4, which are expressed on myeloid cells in the tumor microenvironment, are implicated in suppressing the anti-tumor immune response 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 who are non-responders to T cell checkpoint inhibitor therapy and, therefore, may play a role in tumor resistance to T cell checkpoint inhibitors. Reversing myeloid suppression, or myeloid reprogramming, represents a promising new therapeutic area of immuno-oncology.

How NGM707 May Help Improve Cancer Patients’ Immune Response

Discovered by NGM scientists through the company’s Biologics Discovery Engine, NGM707 is designed to potentially improve patient immune responses to tumors by inhibiting both the ILT2 and ILT4 receptors. In preclinical studies of NGM707, NGM has demonstrated that an ILT4-mediated blockade reverses myeloid cell immune suppression, while an ILT2-mediated blockade 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 act synergistically to reverse suppression of Fc receptor signaling.

Supportive Clinical Data and Development Status

In April 2024, NGM presented encouraging findings from the Phase 1 Part 1b dose escalation cohort of an ongoing Phase 1/2 trial evaluating NGM707 in combination with pembrolizumab, an anti-PD-1 inhibitor, for the treatment of patients with advanced or metastatic solid tumors, at the American Association for Cancer Research (AACR) Annual Meeting. The combination of NGM707 and pembrolizumab was generally well tolerated at all dose levels of NGM707. The maximum tolerated dose was not reached.

AACR 2024 Presentation Highlights:

  • Of 39 response-evaluable patients, best overall responses to date a pathological complete response (pCR) in one patient, partial responses (PR) in four patients, and stable disease in 12 patients, representing a disease control rate (DCR) of ~44%.
  • 12 patients had reduced target lesion (TL) size with a maximum reduction of 100%.
  • Out of the five patients who had a pCR or PR, four patients were pre-treated with anti-PD1/anti-PD-L1.
  • Two patients with microsatellite stable, or MSS, colorectal cancer achieved confirmed PR, one of them with TL reduction that allowed subsequent surgical resection of all gross residual disease and confirmed pCR with no active tumor cells and circulating tumor DNA, or ctDNA, below detection.