NGM Bio Pinpoints Fourth Antibody Drug Candidate for Oncology Therapy Development

NGM Biopharmaceuticals, a US-based biotechnology company, disclosed a fourth oncology development candidate on Aug. 23, 2021. The new candidate, NGM831, is an antagonist antibody designed to block the interaction between immunoglobulin-like transcript 3 (ILT3) and fibronectin, as well as other ligands.

NGM Bio plans to initiate first-in-human testing of the candidate in the first half of 2022. The company started a Phase I/II study of a previous candidate, NGM707, in July 2021 to investigate (the efficacy/safety or both?) that candidate when administered solo or in combination with KEYTRUDA (pembrolizumab) in patients with advanced solid tumors. The company also plans to initiate a Phase I study of another previous candidate, NGM438, in advanced solid tumors in the first half of 2022.

The announcement of the fourth oncology candidate coincides with a paper published in Cancer Immunology Research, a journal of the American Association for Cancer Research (1) that described the discovery of fibronectin, a functional ligand for ILT3, and an extracellular matrix protein that forms a fibrillar network within the tumor stroma. According to the publication, ILT3 is a fibronectin-binding inhibitory immune receptor that receives signals from the extracellular matrix causing it to directly promote myeloid cell suppression. ILT3 is expressed specifically on tumor-associated myeloid cells, and particularly high expression has been found on tolerogenic dendritic cells (DCs), myeloid-derived suppressor cells, and M2 macrophages.

This discovery enabled NGM Bio to develop NGM831, which is expected to reprogram tolerogenic DCs into stimulatory cells by enhancing fragment crystallizable region receptor activity. The candidate is also expected to enhance T cell infiltration and activation. In addition to this fourth candidate, NGM Bio’s oncology portfolio includes NGM120 (anti-GFRAL), NGM707 (anti-ILT2/ILT4), and NGM438 (anti-LAIR1).

“The work we published on the ILT3–fibronectin pathway and our unveiling of NGM831 is yet another proof point of our robust in-house capabilities to deeply interrogate biology and rapidly translate our discoveries into investigational medicines designed to bring hope and meaningful change to patients with cancer and other serious diseases,” said David J. Woodhouse, CEO of NGM Bio, in a company press release. “With oncology programs now targeting ILT2/ILT4, ILT3, and LAIR1 [leukocyte associated immunoglobulin-like receptor 1], we have constructed a comprehensive myeloid reprogramming strategy that is directed at multiple and distinct targets. Our planned biomarker strategy across the NGM707, NGM831, and NGM438 clinical development programs will help inform target patient populations for each product candidate.”

“NGM [Bio] has a strong track record of identifying important ligand-receptor interactions, thereby opening the door to impactful therapeutics,” said Alex DePaoli, chief translational officer at NGM Bio, in the press release. “We are pleased to showcase how our team of scientists identified ILT3’s functional ligand, fibronectin, and subsequently designed an antibody specifically tailored against the target. By inhibiting ILT3’s interaction with fibronectin, NGM831 represents another potential approach to mobilize a patient’s own immune system to fight tumors by shifting myeloid cells from a suppressive state to a stimulatory state and promoting antitumor immunity.”

Reference

1. K.J. Paavola, et al., Cancer Immunol Res (Aug. 23, 2021).

Source: NGM Biopharmaceuticals