- 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.
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.