NextCure, Inc. announced new data from two clinical studies and one research study presented at the Society for Immunotherapy of Cancer (SITC) annual meeting in Washington, D.C., and on a virtual platform. The data come from clinical studies evaluating NC318, a Siglec-15 (S15) antibody, and NC410, a fusion protein of LAIR-2, in patients with advanced/metastatic solid tumors, as well as from a research study evaluating NC410?s impact on T cell activation and myeloid cell polarization conducted in collaboration with the National Cancer Institute at the National Institutes of Health. Clinical benefit through S15 targeting with NC318 antibody in subjects with S15 positive advanced solid tumors. Combined Phase 1 and Phase 2 data from the NC318 study show early evidence of possible clinical benefit in patients with lung cancer, squamous cell carcinoma of the head and neck and breast cancer and other advanced/metastatic solid tumors with dosing once every two weeks during dose escalation and with the 400mg dose selected for the Phase 2 studies. Highlights include: Data are derived from patient cohorts in both Phase 1 (n=49) and Phase 2 (n=47) of these studies. One NSCLC CR and one NSCLC PR patient from the Phase 1 study remain on therapy for 2.8 and 2.2 years, respectively. NC318 appears to show evidence of disease control with better outcomes in S15+ patients compared to S15- patients. The disease control rate across all tumors in both studies was 37% with a median progression-free survival (PFS) of 5.0 months. Patients in the lung cohort from both studies showed 45% disease control rate with a median PFS of 5.2 months. Data indicate that soluble S15 (sS15) level may serve as a biomarker for patient selection. Pharmacokinetic and pharmacodynamic modeling predict that a dose of 800 mg once a week results in nearly 10 times greater drug exposure which may impact drug activity and clinical outcomes. NC410, a fusion protein of LAIR-2 (Leukocyte Associated Immunoglobulin-like Receptor) fused to human IgG1 Fc domain appears safe and well-tolerated with evidence of immune modulation in subjects with advanced solid tumors. Interim data presented from the Phase 1 dose-escalation study show that NC410 appears to be safe and well-tolerated in patients with advanced tumors and show evidence of immune modulation. Highlights include: The data come from the first five patient cohorts (n=19), who received doses of NC410 up to 60 mg once every two weeks. There were no dose-limiting toxicities. Data show a transient reduction in peripheral C1q, suggesting target binding of NC410. LAIR-2 levels in peripheral blood increase in a dose-dependent fashion and may suggest mechanistic evidence of immune normalization. Early evidence of extracellular matrix (ECM) remodeling and immune activation was shown by an increase in serum C4G, a Granzyme B-mediated collagen fragment, and a reduction in serum Pro-C3 and Pro-C6 fragments. Time-dependent increase in CD4+ and CD8+ T cells without an increase in LAIR-1 expression provides further early evidence of immune activation. Safety, tolerability, efficacy, and biomarker analyses are ongoing in higher dose cohort patients. Blockade of the inhibitory collagen receptor LAIR-1, PD-L1, and TGF-? promotes anti-tumor activity through T cell activation and myeloid cell polarization. Non-clinical data from a research study conducted in collaboration with the National Cancer Institute at the National Institutes of Health show NC410?s impact on T cell activation, myeloid cell polarization and anti-tumor activity. Highlights include: NC410 and bintrafusp alpha, a TGF-beta trap molecule, synergize for effective tumor control in a mouse model of colon cancer. Tumor control is mediated by an increase in activated CD8+ T cells and a reduction in M2 tumor-associated macrophages in tumor infiltrates. Collagen remodeling is demonstrated in tumors treated with NC410.