Preclinical Data Demonstrate Anti-Siglec-15 Treatment Reduced Bone Loss and Enhanced Bone Quality in Mice with Moderate-to-Severe Osteogenesis Imperfecta (OI)
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 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:
- Treatment 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.
“We previously demonstrated that the surrogate antibody, NP159 (murine mAb parent to NC605) improved bone quality and decreased fractures in female oim. To address potential differences in therapeutic effects given sexual dimorphism seen with OI, we have now extended the study to evaluate and demonstrate efficacy in male oim,” said
The data were generated in collaboration with Dr.
Title: Sexual Dimorphism in Treatment Effect of Anti-Siglec 15 in Adult Mice with Moderate-to-Severe Osteogenesis Imperfecta
Abstract No: LB SUN-655
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NextCure is a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases. Through our proprietary FIND-IO™ platform, we study various immune cells to discover and understand targets and structural components of immune cells and their functional impact in disease in order to develop immunomedicines. Our focus is to bring hope and new treatments to patients who do not respond to current cancer therapies, patients whose cancer progresses despite treatment and patients with cancer types not adequately addressed by available therapies. http://www.nextcure.com
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