Preclinical Data Demonstrate Anti-Siglec-15 Treatment Improves Bone Microarchitecture and Reduces Fracture Incidence in Mice with Moderate-to-Severe Osteogenesis Imperfecta

Rhea-AI Summary

NextCure (Nasdaq: NXTC) presented promising preclinical data for NC605, their novel anti-Siglec-15 antibody treatment for osteogenesis imperfecta (OI), also known as brittle bone disease. The study demonstrated that NP159 (the murine version of NC605) improved bone microarchitecture and reduced fracture incidence compared to anti-sclerostin treatment in OI mice.

Key findings showed that weekly treatment with 20 mg/kg of NP159 increased cortical and trabecular bone mineral density, tissue mineral density, and cortical thickness while decreasing trabecular separation compared to control groups. The research was conducted in collaboration with Dr. Cathleen Raggio from Hospital for Special Surgery, New York. NextCure is now seeking financial partners to advance NC605 toward an IND submission within 12-18 months.

Positive

• Preclinical data showed improved bone microarchitecture and reduced fracture incidence
• NC605 demonstrated dual action: inhibiting bone loss while producing new bone with increased quality
• Results were comparable to anti-sclerostin treatment, suggesting competitive efficacy
• Potential first-in-class treatment for an indication with no FDA-approved standard of care

Negative

• Company requires external financial support to advance NC605 to IND stage
• Early-stage development (preclinical) indicates long pathway to potential commercialization

BELTSVILLE, Md., July 24, 2025 (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 new preclinical data in a well-established model of osteogenesis imperfecta (OI) demonstrating that treatment with NC605, a novel anti-Siglec-15 antibody, achieved improved bone microarchitecture and reduced fracture incidence compared to anti-sclerostin treatment. The data were presented at the Brittle Bone Society Meeting on July 24^th, 2025. These results demonstrate that NC605 could be a highly effective treatment for OI, also known as brittle bone 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 has been shown to inhibit bone loss and to produce new bone, with increased quality and density.

Fracture incidence and bone architecture were assessed in male and female OI mice treated with weekly 20 mg/kg of surrogate antibody NP159 (murine mAb parent to NC605) and compared to control groups treated with twice weekly 50 mg/kg anti-sclerostin or saline. NP159 increased cortical and trabecular bone mineral density, tissue mineral density, cortical thickness and decreased trabecular separation compared to saline-treated mice.

“In a mouse model of moderate-to-severe OI, NP159, a surrogate murine antibody for NC605, improved trabecular and cortical bone density and reduced fracture incidence comparable to anti-sclerostin,” said Priyanka Kothari, Ph.D., NextCure’s Director, Translational Research. “There is currently no standard of care approved by the FDA for patients with OI and NC605 has the potential to provide significant therapeutic benefit for patients.”

The data were generated in collaboration with Dr. Cathleen Raggio, Hospital for Special Surgery, New York.

NextCure is seeking financial support from partners or third parties to advance NC605 to a possible Investigational New Drug submission within 12 to 18 months.

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 findings of NextCure's (NXTC) NC605 preclinical trial for osteogenesis imperfecta?

The trial showed that NC605's surrogate antibody NP159 improved bone mineral density, tissue mineral density, and cortical thickness while reducing fracture incidence in OI mice, with results comparable to anti-sclerostin treatment.

How does NextCure's NC605 treatment differ from current osteogenesis imperfecta treatments?

Unlike current anti-resorptive treatments that inhibit both bone loss and formation, NC605 uniquely inhibits bone loss while simultaneously promoting new bone formation with increased quality and density.

What is the development timeline for NextCure's (NXTC) NC605 treatment?

NextCure is seeking financial partners to advance NC605 toward an Investigational New Drug (IND) submission within the next 12-18 months.

What dosing regimen was used in NextCure's preclinical study of NC605?

The study used weekly doses of 20 mg/kg of NP159 (the murine version of NC605), compared to twice-weekly 50 mg/kg anti-sclerostin or saline in the control groups.

What is the current treatment landscape for osteogenesis imperfecta?

There is currently no FDA-approved standard of care for osteogenesis imperfecta. Existing anti-resorptive treatments increase bone density but result in overall poor bone quality.