NextCure, Inc. (NASDAQ:NXTC), a clinical-stage biopharmaceutical company discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases, today announced the publication of preclinical data in the online journal eLife establishing NC410 as a novel immunomedicine targeting immune-excluded regions of collagen-rich tumors and enabling normalization of the tumor immune microenvironment. NC410, currently being evaluated in a Phase 1/2 clinical trial in patients with advanced or metastatic solid tumors, is a first-in-class immunomedicine designed to block immune suppression mediated by LAIR-1, an immunomodulatory receptor expressed on T cells and myeloid cells, including dendritic cells.
“The blockade of LAIR-1 binding to collagen in the tumor microenvironment (TME) by NC410 represents a novel mechanism for targeting immune-excluded regions of tumors, including those with poor response to immunotherapy due to dense regions of collagen in tumors,” said Michael Richman, NextCure’s president and chief executive officer. “We believe NC410 is a valuable asset in NextCure’s growing pipeline of innovative immunomedicines, and we look forward to continuing to evaluate NC410 in our Phase 1/2 clinical study as well as reporting initial clinical data in the second half of this year.”
“The interaction between immune cells expressing LAIR-1 in collagen rich regions of a tumor suppresses immune activation and prevents immune cells from entering the parenchyma of the tumors, therefore preventing anti-tumor immunity,” said Dallas Flies, Ph.D., NextCure’s Vice President of Discovery Research. “This immune-excluded phenotype is common in multiple cancer indications that are not adequately addressed by checkpoint immunotherapy. Data from our preclinical studies revealed that NC410 promotes T cell mediated anti-tumor immunity as well as infiltration and localized activity of T cells in the TME, suggesting its potential as a cancer monotherapy or combination therapy with checkpoint inhibitors particularly for immune-excluded, collagen-rich tumors.”
The publication titled, “Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking LAIR-collagen interaction,” details the preclinical development and characterization of NC410. It also highlights preclinical data from a series of murine xenograft efficacy studies demonstrating anti-tumor activity and the promotion of T cell expansion and infiltration in the TME by NC410.
NC410 is a dimeric LAIR-2 Fc fusion protein that is designed to act as a LAIR-1 decoy by binding with higher affinity to tumoral collagens than human LAIR-1, preventing LAIR-1-mediated immune suppression. This publication demonstrated that NC410 binding was most notable in collagen-rich tumors, such as gastric, ovarian, lung and head and neck, and in regions where immune cells were being excluded. As a result of T cell activation and effector function, NC410 induces specific collagen degradation products that may relate to the enhanced infiltration of immune cells in the tumor and have the potential to be used as clinical biomarkers.
The paper was published in collaboration with Linde Meyaard, Ph.D., principal investigator at the Center for Translational Immunology, University Medical Center Utrecht, and an Oncode Investigator at Oncode Institute, who identified the inhibitory immune receptor LAIR-1 and has been working on it for over 20 years. The paper can be accessed from eLife’s website at http://www.elifesciences.org.
