Preclinical Data Demonstrate Anti-Siglec-15 Treatment Reduced Bone Loss and Enhanced Bone Quality in Mice with Moderate-to-Severe Osteogenesis Imperfecta (OI)
17 Octubre 2023 - 7:05AM
NextCure, Inc. (Nasdaq: NXTC), a clinical-stage
biopharmaceutical company committed to discovering and developing
novel, first-in-class immunomedicines to treat cancer and other
immune-related diseases, today 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.
NextCure 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:
- 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 Solomon Langermann, Ph.D., NextCure’s chief scientific
officer. “Given the unique properties of NC605 to improve bone
quality, and reduce fractures, coupled with its safe profile, NC605
holds great promise as a potential transformative agent needed to
provide treatment for OI patients throughout their life, including
both female and male patients.”
The data were generated in collaboration with Dr. Cathleen
Raggio, Hospital for Special Surgery, New York. The data were
presented in a poster presentation by Dr. Raggio at the 2023
American Society for Bone and Mineral Research.
Title: Sexual Dimorphism in Treatment Effect of
Anti-Siglec 15 in Adult Mice with Moderate-to-Severe Osteogenesis
ImperfectaAbstract No: LB SUN-655
About NextCure, Inc.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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Investor InquiriesTimothy Mayer, Ph.D.NextCure,
Inc.Chief Operating Officer(240) 762-6486IR@nextcure.com
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