INBRX-109

INBRX-109 is a multivalent agonist of death receptor 5, or DR5, developed with the Inhibrx sdAb platform. Agonism, or clustering, of DR5 receptors initiates a signaling pathway within the cell leading to tumor cell specific apoptosis, or programmed cell death. The process of clustering multiple cell surface receptors in close proximity to one another is essential for the induction of efficient signaling within a cell. Previously explored approaches using conventional mAbs or recombinant tumor necrosis factor-related apoptosis-inducing ligand, TRAIL, to target DR5 resulted in limited clinical efficacy, which we believe was due to an inability to effectively cluster multiple receptors. Additionally, clinical investigation of a multivalent DR5 agonist was halted due to observed liver toxicity. Based on published reports and internally generated data, we believe this toxicity was caused by anti-drug antibody (ADA) mediated hyper-clustering of DR5. To overcome the challenge of generating effective clustering while avoiding ADA-mediated toxicity, we designed INBRX-109 to cluster exactly four DR5 receptors per molecule and removed sequences that are recognized by pre-existing anti-sdAb antibodies commonly present in humans. We believe INBRX-109 has the potential to show clinical activity in multiple tumor types, including difficult-to-treat gastrointestinal tumors and mesothelioma. In addition, we believe INBRX-109 has the potential to act as both a single agent and in combination with apoptotic pathway modulators or chemotherapy. INBRX-109 is currently being investigated in a Phase 1 clinical trial in patients with solid tumors including sarcomas. We expect to announce interim results from the dose escalation part of this trial in the first half of 2019.