Maryland-based biotech NextCure is looking for partners to advance a candidate for the currently incurable rare disease osteogenesis imperfecta (OI) after the asset strengthened bones and reduced fractures in mice with the condition.
Also called brittle bone disease, patients with OI have weakened bones that fracture easily and often lead to physical symptoms like bowing legs, spine curvature, loose joints and muscle weakness. Treatment involves managing symptoms and trying to prevent bone breaks as much as possible.
NextCure compared a mouse version of antibody NC605 to an anti-sclerostin, a class of drug that blocks the breakdown of bone. One anti-sclerostin, Amgen’s Evenity (romosozumab-aqqg), is approved for postmenopausal women with osteoporosis, while another from Ultragenyx and Mereo BioPharma is currently in a phase 3 trial for OI.
NextCure’s antibody “improved trabecular and cortical bone density and reduced fracture incidence comparable to anti-sclerostin,” the company’s director of translational research, Priyanka Kothari, Ph.D., said in a July 24 release. “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.”
Cortical tissue forms the tough exterior of bones, while trabeculae are spongelike structures found at the ends of long bones like the femur and inside bones with specialized shapes like vertebrae.
Instead of targeting sclerostin, NC605 is designed to bind to Siglec-15, a receptor found on the surface of bone cells called osteoclasts. Osteoclasts clean out old or damaged bone tissue so that their partner cells, osteoblasts, can lay down new bone in its place. Inhibiting Siglec-15 has been found to halt this process of bone destruction.
NextCure has also tested NC605 preclinically in acute spinal cord injuries. The biotech dropped another anti-Siglec-15 antibody, NC318, in 2022 after the asset showed no promise as a cancer monotherapy in a phase 1/2 trial. The company said at the time it was still supporting Yale University’s ongoing trial of NC318 in combination with Merck’s Keytruda (pembrolizumab) in advanced non-small cell lung cancer.
The company hopes to submit an investigational new drug application for NC605 in about 12 to 18 months and is actively “seeking financial support from partners or third parties” to do so, according to the release. The company first announced plans to seek partners for NC605 and other assets in November 2024 as part of a refocusing on its tumor-targeting ADCs. NextCure has two ADCs currently in phase 1 trials, according to its website.