Preclinical Data Demonstrates Anti-Siglec-15 Treatment Enhanced Generation of Quality Bone with Better Mechanical Properties in Mice with Moderate-to-Severe Osteogenesis Imperfecta

Rhea-AI Summary

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.

Positive

• 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

Negative

• Treatment benefits were less pronounced in female mice compared to males
• Results are only preclinical stage, requiring further clinical validation

Insights

Medical Research Analyst

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 90% and 80% fracture-free rates in male and female mice respectively.

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 15^th, 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 and 80% of female oim, had no fractures post-sacrifice, compared to 85% and 55% 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

Cautionary Statement Regarding Forward-Looking Statements

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

FAQ

What were the key results of NextCure's (NXTC) NC605 treatment in OI mice?

The treatment resulted in 90% of male and 80% of female mice showing no fractures, increased trabecular and cortical tissue mineral density in both sexes, and improved mechanical bone strength specifically in male mice.

How does NextCure's (NXTC) NC605 differ from current OI treatments?

Unlike current anti-resorptive treatments that inhibit both bone loss and formation, NC605 inhibits bone loss while enhancing osteoblast recruitment to produce new bone, resulting in better quality bone with increased density.

What was the dosage used in NextCure's (NXTC) OI mouse study?

The study used 20 mg/kg of surrogate antibody NP159, which is the murine antibody parent to NC605.