NextCure, Inc. has announced promising preclinical results for NC605, a novel anti-Siglec-15 antibody, in treating osteogenesis imperfecta (OI), a rare disorder characterized by bone fragility and recurrent fractures. The data, presented at the Brittle Bone Society Meeting on July 24, 2025, demonstrate that NC605 achieved improved bone microarchitecture and reduced fracture incidence compared to anti-sclerostin treatment in a well-established mouse model of moderate-to-severe OI.
Novel Mechanism Addresses Treatment Limitations
Osteogenesis imperfecta, also known as brittle bone disease, results in high bone turnover, abnormal bone formation, bone fragility and recurrent fractures. Currently, there is no cure for OI, and existing anti-resorptive treatments present significant limitations. These current therapies inhibit both bone loss and bone formation, leading to increased bone density but overall poor bone quality.
NC605 offers a differentiated approach by both inhibiting bone loss and producing new bone with increased quality and density. This dual mechanism represents a potential advancement over current treatment paradigms that compromise bone formation while addressing bone loss.
Preclinical Study Results
The study assessed fracture incidence and bone architecture in male and female OI mice treated with weekly 20 mg/kg doses of surrogate antibody NP159, the murine monoclonal antibody parent to NC605. Results were compared to control groups receiving twice weekly 50 mg/kg anti-sclerostin or saline treatments.
NP159 treatment demonstrated significant improvements across multiple bone health parameters compared to saline-treated mice, including increased cortical and trabecular bone mineral density, enhanced tissue mineral density, greater cortical thickness, and decreased trabecular separation.
"In a mouse model of moderate-to-severe OI, NP159, a surrogate murine antibody for NC605, improved trabecular and cortical bone density and reduced fracture incidence comparable to anti-sclerostin," said Priyanka Kothari, Ph.D., NextCure's Director of Translational Research.
Addressing Unmet Medical Need
The research addresses a significant unmet medical need in the OI patient population. As Kothari noted, "There is currently no standard of care approved by the FDA for patients with OI and NC605 has the potential to provide significant therapeutic benefit for patients."
The preclinical work was conducted in collaboration with Dr. Cathleen Raggio from Hospital for Special Surgery in New York, lending additional credibility to the research findings.
Development Timeline and Next Steps
NextCure is actively seeking financial support from partners or third parties to advance NC605 toward clinical development. The company aims to submit an Investigational New Drug application within 12 to 18 months, representing a critical milestone in bringing this potential therapy to patients.
The clinical-stage biopharmaceutical company, primarily focused on cancer therapeutics, is expanding its pipeline to address rare diseases through its expertise in biological pathways and biomarkers. NextCure's approach leverages understanding of cellular interactions, including those in specialized microenvironments, to develop differentiated therapeutic mechanisms.
