NGM Discloses Third Oncology Development Candidate, NGM438, a Novel Antagonist Antibody Inhibiting LAIR1 for the Treatment of Advanced Solid Tumors

  • LAIR1, through interactions with tumor-associated collagens, may form a stromal checkpoint that imposes signaling-based immune suppression and impedes anti-tumor immunity
  • NGM plans to initiate first-in-human testing of NGM438 in 4Q21
  • NGM featured NGM438 today at its first R&D Day, along with its diverse pipeline of drug candidates for liver and metabolic diseases, retinal diseases and cancer

SOUTH SAN FRANCISCO, CA, USA I December 09, 2020 I NGM Biopharmaceuticals, Inc. (NGM) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today disclosed its third oncology development candidate, NGM438, a novel antagonist antibody that inhibits Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1). NGM438 was featured earlier today during NGM’s first R&D Day. The event highlighted the company’s diverse portfolio of therapeutic candidates for liver and metabolic disease, retinal diseases and cancer. All presentations from the R&D Day can be found in the Investors & Media section of NGM’s website here.

LAIR1 is a collagen-binding inhibitory receptor expressed on immune cells1-2 that is implicated in immune suppression. LAIR1 and collagens are upregulated in multiple cancer types3-7 where collagens are produced by activated stromal cells. These stromal-derived suppressive factors are associated with poor responses to checkpoint inhibitors. For such tumors, formation of the LAIR1-collagen complex may act as a stromal checkpoint to both physically exclude immune cells from the tumor and impose signaling-based immune suppression8-9. Consequently, inhibiting this stromal checkpoint represents a potentially promising new therapeutic strategy to treat cancer by promoting the remodeling of the tumor architecture that restricts T cell infiltration of the tumor cell mass and reversing immune suppression in the tumor microenvironment.

Designed to inhibit LAIR1 interactions with stromal-derived collagens, NGM438 has the potential to block this stromal checkpoint and restore anti-tumor immune responses. In preclinical studies, NGM438 demonstrated the ability to reprogram collagen-suppressed myeloid cells to a stimulatory phenotype, induce inflammatory cytokine production by myeloid and T cells, and relieve collagen-based suppression of T cell proliferation. Reinvigoration of collagen-suppressed immune cells may address a key resistance mechanism that limits responses to current immunotherapies.

“At NGM’s inaugural R&D Day today, we were excited to showcase NGM’s powerful in-house drug discovery engine. NGM438, a novel immuno-oncology candidate, is yet another example of our team’s biology-driven approach and expertise in tailoring highly-specialized antibodies,” said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM. “NGM438, which inhibits LAIR1, and NGM707, our dual antagonist antibody that inhibits ILT2 and ILT4, are both examples of our strategy to broaden and deepen anti-tumor immune responses for patients through myeloid reprogramming by addressing key resistance mechanisms and reversing stromal and myeloid checkpoints.”

NGM438 joins NGM707 as the second myeloid reprogramming product candidate in the NGM oncology portfolio. NGM707 is a novel dual antagonist antibody that inhibits Immunoglobulin-like transcript 2 (ILT2) and Immunoglobulin-like transcript 4 (ILT4). First-in-human testing for NGM707 is expected to begin in mid-2021. NGM’s third oncology candidate is 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. NGM120 is in an ongoing Phase 1a/1b trial in patients with cancer and cancer anorexia/cachexia syndrome (CACS).

NGM438, NGM707 and NGM120 were discovered by NGM under its strategic collaboration with Merck.

About NGM Biopharmaceuticals, Inc.

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 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. Visit us at www.ngmbio.com for more information.

  1. Meyaard, Immunity, 1997
    2. Guo, Trans Med, 2020
    3. Cao, 2015, Biochem Biophys Res Commun
    4. Wang, Exp Ther Med, 2016
    5. Wu, CP Cancer, 2018
    6. Yang, Head & Neck, 2018
    7. Jingushi, Onc. Reports, 2018
    8. Peng, Nat Comm, 2020
    9. Lijun, Oncoimmunology, 2020

SOURCE: NGM Biopharmaceuticals

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