Inhibrx Biosciences and Ozekibart: A First-Mover in Targeted Oncology with Expansive Potential

The oncology landscape in 2025 is defined by a shift toward precision therapies, with companies leveraging novel mechanisms to address high-unmet-need indications. Among the most promising candidates is Ozekibart (INBRX-109), a tetravalent death receptor 5 (DR5) agonist antibody developed by Inhibrx Biosciences. While its groundbreaking results in chondrosarcoma have already captured attention, the drug's potential to expand into other oncology indications-such as colorectal cancer and Ewing sarcoma-positions Inhibrx as a leader in a nascent but rapidly evolving therapeutic class.

Mechanism of Action and Clinical Efficacy in Chondrosarcoma

Ozekibart's mechanism of action centers on activating DR5, a tumor necrosis factor (TNF) superfamily receptor that selectively induces apoptosis in cancer cells while sparing healthy tissue according to clinical data. This specificity has translated into robust clinical outcomes. In the pivotal ChonDRAgon trial for advanced chondrosarcoma, ozekibart achieved a 52% reduction in the risk of disease progression or death compared to placebo, with a median progression-free survival (PFS) of 5.52 months versus 2.66 months as reported in the trial. These results, observed across both IDH-wild-type and IDH-mutant subgroups, underscore its potential as a first-line treatment in a disease where no systemic therapies are currently approved.

Expansion into High-Unmet-Need Indications

Beyond chondrosarcoma, ozekibart is being evaluated in combination regimens for other cancers with limited therapeutic options. In colorectal cancer (CRC), where third- and fourth-line treatments remain palliative, ozekibart combined with FOLFIRI demonstrated a 23% overall response rate (ORR) and a 92% disease control rate in heavily pretreated patients according to clinical results. Similarly, in refractory Ewing sarcoma, a rare and aggressive pediatric cancer, ozekibart in combination with irinotecan and temozolomide achieved a 64% ORR and a 92% disease control rate, significantly outperforming the standard of care as detailed in the trial. These results highlight ozekibart's ability to address unmet needs in patient populations with poor prognoses and limited treatment alternatives.

First-Mover Advantage in DR5 Agonist Therapies

Inhibrx's leadership in the DR5 agonist space is further reinforced by the absence of approved competitors. As of late 2025, no DR5 agonist has received regulatory approval, leaving ozekibart as the most advanced candidate in this class according to industry analysis. This first-mover advantage is critical, as DR5 agonists represent a novel approach to inducing tumor-specific apoptosis, particularly in cancers with high DR5 expression. Inhibrx's strategic focus on combination therapies-pairing ozekibart with chemotherapies like FOLFIRI and irinotecan-also differentiates it from traditional monotherapies, which often face resistance or toxicity challenges.

Regulatory and Strategic Milestones

Inhibrx is poised for key regulatory milestones in 2026. The company plans to file a biologics license application (BLA) for ozekibart in chondrosarcoma by Q2 2026, following the completion of its registrational trial as announced. Additionally, it aims to engage the FDA in discussions for accelerated approval in Ewing sarcoma, leveraging the strong response rates observed in its expansion cohorts according to company plans. These steps align with a broader strategy to establish ozekibart as a cornerstone therapy in multiple solid tumor indications.

Broader Competitive Landscape and Precision Oncology Trends

While ozekibart's DR5 mechanism is unique, the broader oncology market in 2025 has seen significant advancements in precision therapies. For instance, sevabertinib, a HER2/EGFR tyrosine kinase inhibitor, received FDA breakthrough therapy designation for non–small cell lung cancer (NSCLC), while zongertinib was approved for HER2-mutant NSCLC as reported by industry sources. Similarly, Dato-DXd, a TROP2-directed antibody-drug conjugate (ADC), demonstrated a 6.9-month improvement in progression-free survival for HR-positive, HER2-negative breast cancer according to clinical data. These approvals reflect the industry's shift toward genotype-directed therapies, a trend that ozekibart aligns with through its targeted mechanism.

Conclusion

Inhibrx Biosciences has positioned ozekibart as a transformative therapy in chondrosarcoma and a promising candidate for expansion into other high-unmet-need cancers. Its first-mover status in the DR5 agonist class, combined with robust clinical data and a clear regulatory pathway, makes it a compelling investment opportunity. As the oncology market continues to prioritize precision and efficacy, ozekibart's potential to redefine treatment paradigms in multiple tumor types could drive significant long-term value for stakeholders.