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The Candidate

Our tetravalent DR5 agonist.

INBRX-109, our tetravalent DR5 agonistic antibody, is designed to exploit tumor-biased direct cell death induction by DR5 activation in numerous cancer types.

With a valency of four, it has the ability to potently agonize DR5 through efficient receptor clustering, causing cell death, but by way of our sdAb platform, also eliminates recognition by pre-existing anti-drug antibodies (ADAs) to lessen the potential for hyper-clustering.

Valency Drives DR5-Mediated Apoptosis

Apoptosis is the death of cells that occurs as a normal and controlled part of an organism’s growth or development. DR5 requires the proper valency to trigger apoptosis of cancer cells—and spare healthy cells.

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Engineered to Avoid Hepatotoxicity

Human Hepatocyte Toxicity Assay

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  • Hepatocytes may be subject to on-target toxicity for DR5 pathway agonism.
  • Previous tetravalent DR5 agonists failed in the clinic due to hepatotoxicity—likely due to hyper-clustering by anti-drug antibodies.
  • In vitro hepatic cell (HepaRG) death assay recapitulates toxicity of TAS266 + pre-existing anti-drug antibodies (PE-ADAs) in pooled human immunoglobulins.
  • Proper valency is key: Hexavalent (Hex-1F5) is also hepatotoxic.
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INBRX-109 Clinical Trial

The Phase 1 trial for INBRX-109 is currently enrolling combination treatment cohorts in Pancreatic Adenocarcinoma, Ewing sarcoma,  colorectal cancer, and Malignant Pleural Mesothelioma.

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The registration-enabling Phase 2 trial for INBRX-109 is currently enrolling patients with unresectable or metastatic conventional chondrosarcoma.

Phase 1 Trial Phase 2 Trial