NextCure, Inc. announced the presentation of new preclinical data demonstrating that treatment with NC605, a novel anti-Siglec-15 (S15) antibody, reduced bone loss and enhanced bone quality in mice with osteogenesis imperfecta (OI), at the 2023 American Society for Bone and Mineral Research (ASBMR) annual meeting. These results support development of NC605 as a potential highly effective treatment for osteogenesis imperfecta, a rare disease in which bones easily fracture. Osteogenesis imperfecta is a rare disorder that results in high bone turnover, abnormal bone formation, bone fragility and recurrent fractures.

There is no cure for OI and current anti-resorptive treatments increase bone mineral density (BMD) primarily by inhibiting bone loss; however, these agents also inhibit bone formation. Unlike anti-resorptive therapies, NC605 enhances osteoblast recruitment, resulting in overall enhanced bone quality. In preclinical testing, NC605 has been shown to prevent bone loss by inhibiting osteoclast maturation and bone resorption by binding S15, which is expressed on the cell surface of immature osteoclasts and upregulated in differentiated osteoclasts.

The company identified NC605 while screening S15 antibodies for anticancer properties. Further characterization revealed that the S15 antibodies without anticancer properties had the ability to inhibit osteoclast maturation and thus may have use in treating bone disease. The number of new bone fractures and bone quality were assessed and compared to control animals and to female OI mice (oim) from a prior study.

Key findings include: reatmentnt with the surrogate antibody, NP159 prevented new bone fractures in 90% of male oim compared to 85% of female oim seen earlier. All control mice had one or more new bone fractures; High resolution microCT showed decreased trabecular bone separation with NP159 treatment in both oim males and females (p=0.05); Cortical bone porosity, a measure of mechanical strength of bone, was normal in the treated male mice, in contrast with females who showed increased porosity; There were no changes in the overall bone mineral density for male or female mice; Bone stiffness increased in both male and female oim; Fourier Transform Infrared (FTIR-I) readouts, a measure of bone quality, in treated females showed a normalization of mineral: matrix ratio, increased acid phosphate and decreased collagen maturity. Interestingly and in contrast, the males showed no similar changes.