NC318 is a monoclonal antibody, a first-in-class immunomedicine, targeting Siglec-15 (S15), a novel immunomodulatory protein which is expressed on highly immunosuppressive cells called M2 macrophages and on tumor cells. In preclinical research, we observed that S15 promotes suppression of T cell proliferation and negatively regulates T cell function. NC318 was designed to block S15-mediated immune suppression and restore T cell function and anti-tumor immunity in the TME, which we believe will reduce and kill tumors. We believe NC318 has the potential to treat multiple cancer indications because S15 is expressed in multiple tumor types and has a unique ability to modulate immune responses in the TME. In addition, because S15 and PD-L1 expression in tumors generally appear to be non-overlapping, we believe NC318 may be well suited to treat patients who are not responding to PD-1/PD-L1 directed cancer therapies. NextCure has initiated clinical phase 1/2 clinical trials with NC318 in patient with advanced or metastatic solid tumors.
NC410, a novel immunomedicine, is a fusion protein of LAIR-2, a naturally occurring soluble version of and decoy protein for LAIR-1, and is designed to block immune suppression mediated by LAIR-1. Multiple preclinical studies support our understanding that eliminating or blocking the binding of LAIR-1 restores normal immune function in multiple immune cells. Our translational work has shown that NC410 blocks the interaction of LAIR-1 with its binding partners, thereby promoting T cell function and dendritic cell activity to contribute to restoring anti-tumor immune activity. Consistent with our strategy, we believe NC410 has the potential to address the needs of patients who are not adequately addressed by currently available therapies. We are currently conducting IND-enabling studies and expect to file an IND and initiate a Phase 1/2 clinical trial in patients with advanced or metastatic solid tumors in patient with advanced or metastatic solid tumors.