NextCure announces publication of non-clinical data on Anti-Siglec-15 treatment

NextCure announced the publication of a manuscript titled “Anti-Siglec-15 Antibody Prevents Marked Bone Loss after Acute Spinal Cord Injury-Induced Immobilization in Rats” in JMBR Plus, a journal of the American Society for Bone and Mineral Research. The data demonstrated that NC605, a novel anti-Siglec-15 antibody, prevented bone loss, but more importantly preserved bone strength in animal models of severe immobilization resulting from acute spinal cord injury. Following spinal cord injury, patients typically suffer rapid and extensive bone loss. While anti-resorptive therapies have shown some efficacy in inhibiting bone loss, these agents also inhibit bone formation. 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. Unlike anti-resorptive therapies, NC605 enhances osteoblast recruitment, resulting in overall enhanced bone quality. In the animal model of spinal cord injury, bone mineral density was assessed and compared to control animals. Key findings from the study include: Treatment with anti-S15 antibody completely prevented loss of BMD in the femur and tibia. High-resolution imaging analysis revealed almost complete prevention of trabecular bone volume loss. Blood and bone structure analyses revealed that the anti-S15 antibody was able to greatly inhibit bone resorption while maintaining bone formation and quality. Ex vivo analysis showed increased numbers of osteoblasts as well as increased levels of mRNA encoding osteocalcin and bone sialoprotein, markers of bone formation and integrity, demonstrating a unique ability of the antibody to reduce osteoclast formation and bone resorption while promoting osteoblast recruitment to maintain bone integrity.