Preclinical Data Demonstrates Anti-Siglec-15 Treatment Enhanced Generation of Quality Bone with Better Mechanical Properties in Mice with Moderate-to-Severe Osteogenesis Imperfecta
NextCure announced preclinical data showing that NC605, their anti-Siglec-15 antibody, enhanced quality bone generation with improved mechanical properties in mice with Osteogenesis Imperfecta (OI). The study used NP159, a surrogate antibody to NC605, at 20 mg/kg dosage. Key results showed 90% of male and 80% of female treated mice had no fractures, compared to 85% and 55% in control groups. Both sexes demonstrated increased trabecular and cortical tissue mineral density. Male mice specifically showed increased trabecular bone volume and cortical thickness, resulting in improved mechanical bone strength.
NextCure ha annunciato dati preclinici che mostrano come NC605, il loro anticorpo anti-Siglec-15, migliori la qualità della generazione ossea con proprietà meccaniche migliorate in topi affetti da Osteogenesi Imperfetta (OI). Lo studio ha utilizzato NP159, un anticorpo surrogato di NC605, alla dose di 20 mg/kg. Risultati chiave hanno mostrato che il 90% dei topi maschi e l'80% delle femmine trattate non presentavano fratture, rispetto all'85% e al 55% nei gruppi di controllo. Entrambi i sessi hanno dimostrato un aumento della densità minerale del tessuto trabecolare e corticale. In particolare, i topi maschi hanno mostrato un aumento del volume osseo trabecolare e dello spessore corticale, con conseguente miglioramento della resistenza meccanica dell’osso.
NextCure anunció datos preclínicos que muestran que NC605, su anticuerpo anti-Siglec-15, mejoró la calidad de la generación ósea con propiedades mecánicas mejoradas en ratones con Osteogénesis Imperfecta (OI). El estudio utilizó NP159, un anticuerpo sustituto de NC605, a una dosis de 20 mg/kg. Resultados clave mostraron que el 90% de los ratones machos y el 80% de las hembras tratadas no tenían fracturas, en comparación con el 85% y el 55% en los grupos de control. Ambos sexos demostraron un aumento en la densidad mineral del tejido trabecular y cortical. Los ratones machos, en particular, mostraron un aumento en el volumen óseo trabecular y el grosor cortical, lo que resultó en una mejora de la resistencia mecánica del hueso.
넥스트큐어(NextCure)는 NC605, 그들의 항-Siglec-15 항체가 골형성부전증(OI)에 걸린 쥐에서 개선된 기계적 특성을 갖춘 골질 향상을 나타내는 전임상 데이터를 발표했습니다. 이 연구에서는 NC605의 대체 항체인 NP159를 20 mg/kg의 용량으로 사용했습니다. 주요 결과에 따르면 치료받은 수컷 쥐의 90%와 암컷 쥐의 80%가 골절이 없었으며, 이는 대조군의 85%와 55%에 비해 높은 수치입니다. 두 성 모두 다공성 및 겉질 조직의 미네랄 밀도가 증가했습니다. 특히 수컷 쥐는 다공성 뼈의 부피와 겉질 두께가 증가하여 기계적 뼈 강도가 개선되었습니다.
NextCure a annoncé des données précliniques montrant que NC605, leur anticorps anti-Siglec-15, a amélioré la qualité de la génération osseuse avec des propriétés mécaniques améliorées chez des souris souffrant d'Ostéogenèse imparfaite (OI). L'étude a utilisé NP159, un anticorps substitutif de NC605, à une dose de 20 mg/kg. Résultats clés ont montré que 90 % des souris mâles et 80 % des souris femelles traitées n'avaient pas de fractures, contre 85 % et 55 % dans les groupes témoins. Les deux sexes ont montré une augmentation de la densité minérale du tissu trabéculaire et cortical. Les souris mâles, en particulier, ont montré une augmentation du volume osseux trabéculaire et de l'épaisseur corticale, entraînant une amélioration de la résistance mécanique des os.
NextCure hat präklinische Daten veröffentlicht, die zeigen, dass NC605, ihr Anti-Siglec-15-Antikörper, die Qualität der Knochenbildung mit verbesserten mechanischen Eigenschaften bei Mäusen mit Osteogenesis imperfecta (OI) verbessert hat. Die Studie verwendete NP159, einen Surrogat-Antikörper von NC605, mit einer Dosierung von 20 mg/kg. Wichtige Ergebnisse zeigten, dass 90 % der behandelten männlichen und 80 % der weiblichen Mäuse keine Frakturen aufwiesen, verglichen mit 85 % und 55 % in den Kontrollgruppen. Beide Geschlechter zeigten eine erhöhte mineralische Dichte des trabekulären und kortikalen Gewebes. Bei männlichen Mäusen zeigte sich insbesondere ein Anstieg des trabekulären Knochenvolumens und der Kortikaldicke, was zu einer verbesserten mechanischen Knochensicherheit führte.
- 90% of male and 80% of female treated mice showed no fractures vs 85% and 55% in control groups
- Treatment increased trabecular and cortical tissue mineral density in both sexes
- Male mice showed improved mechanical bone strength and increased cortical thickness
- Treatment benefits were less pronounced in female mice compared to males
- Results are only preclinical stage, requiring further clinical validation
Insights
The preclinical data for NC605 represents a significant scientific advancement in treating Osteogenesis Imperfecta (OI). The key differentiator is the dual mechanism - inhibiting bone loss while enhancing new bone formation - which addresses a major limitation of current treatments that only focus on bone density. The data shows impressive efficacy with
The gender-specific outcomes, particularly enhanced bone mechanical properties in males, suggest potential stratification strategies for future clinical trials. While both sexes showed improved bone mineral density, the male-specific benefits in trabecular architecture and mechanical strength warrant careful consideration for human trials. The collaboration with HSS, a leading orthopedic institution, adds credibility to these findings.
BELTSVILLE, Md., Nov. 19, 2024 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class and best-in-class therapies to treat cancer, today announced the presentation of preclinical data demonstrating that treatment with NC605, a novel anti-Siglec-15 (S15) antibody, resulted in enhanced generation of quality bone with better mechanical properties, in an oral presentation at the Osteogenesis Imperfecta Federation Europe virtual Investigator Meeting on November 15th, 2024. These results demonstrate that NC605 is a highly effective treatment for Osteogenesis Imperfecta (OI), also known as brittle bone disease in a well-established model of disease.
OI is a rare disorder that results in high bone turnover, abnormal bone formation, bone fragility and recurrent fractures. There is no cure for OI. Current anti-resorptive treatments inhibit both bone loss and bone formation leading to an increase in bone density, but overall poor bone quality. In contrast, NC605 inhibits bone loss and enhances osteoblast recruitment, to produce new bone, resulting in the generation of quality bone with increased density.
Fracture incidence and bone quality were assessed in male and female OI mice (oim) treated with 20 mg/kg of surrogate antibody NP159 (murine mAb parent to NC605) and compared to control groups. Key findings include:
- In the treated mice,
90% of male oim and80% of female oim, had no fractures post-sacrifice, compared to85% and55% in the control groups, respectively. - For the treated oim population, both sexes showed:
- Increased trabecular and cortical tissue mineral density.
- Increased cortical bone mineral density.
- Collectively, all changes resulted in overall enhanced bone quality with better mechanical properties.
- In contrast, only the treated male oim population showed:
- Increased trabecular bone volume fraction, including an increase in the number of trabeculae and a decreased separation between trabeculae.
- Increased cortical thickness.
- Collectively, the changes resulted in an increase of max load and stiffness, measures of mechanical bone strength.
“We have again demonstrated that, NP159, a surrogate murine antibody for NC605, reduces fracture incidence in both male and female OI mice. Given sexual dimorphism seen with OI, we noted improved bone quality in the treated male mice specifically,” said Solomon Langermann, Ph.D., NextCure’s chief scientific officer. “We continue to believe that NC605 has the potential to be a transformative agent for both female and male OI patients.”
The data were generated in collaboration with Dr. Cathleen Raggio, Hospital for Special Surgery, New York.
About NextCure, Inc.
NextCure is a clinical-stage biopharmaceutical company that is focused on advancing innovative medicines that treat cancer patients that do not respond to, or have disease progression on, current therapies, through the use of differentiated mechanisms of actions including antibody-drug conjugates, antibodies and proteins. We focus on advancing therapies that leverage our core strengths in understanding biological pathways and biomarkers, the interactions of cells, including in the tumor microenvironment, and the role each interaction plays in a biologic response. http://www.nextcure.com
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Statements made in this press release that are not historical facts are forward-looking statements. Words such as “expects,” “believes,” “intends,” “hope,” “forward” and similar expressions are intended to identify forward-looking statements. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those projected in any forward-looking statement. Such risks and uncertainties include, among others: our limited operating history and no products approved for commercial sale; our history of significant losses; our need to obtain additional financing; risks related to clinical development, including that early clinical data may not be confirmed by later clinical results; risks that pre-clinical research may not be confirmed in clinical trials; risks related to marketing approval and commercialization; and NextCure’s dependence on key personnel. More detailed information on these and additional factors that could affect NextCure’s actual results are described in NextCure’s filings with the Securities and Exchange Commission (the “SEC”), including NextCure’s most recent Form 10-K and subsequent Form 10-Q. You should not place undue reliance on any forward-looking statements. NextCure assumes no obligation to update any forward-looking statements, even if expectations change.
Investor Inquiries
Timothy Mayer, Ph.D.
NextCure, Inc.
Chief Operating Officer
(240) 762-6486
IR@nextcure.com
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