INBRX-109

INBRX-109 is a multivalent agonist of death receptor 5, or DR5, which we developed utilizing our 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 to induce efficient signaling within a cell. Previously explored approaches using conventional mAbs or a recombinant tumor necrosis factor-related apoptosis-inducing ligand to target DR5 showed limited clinical efficacy, which we believe was due to an inability to effectively cluster multiple receptors together. To enhance clustering, a tetravalent DR5 agonist, TAS266, was developed by a third party and showed more potency in multiple preclinical models. Despite promising preclinical data, dose-limiting toxicities were observed, which may have resulted from pre-existing anti-drug antibodies to TAS266. To overcome the limitations of ineffective clustering, we designed INBRX-109 as a tetravalent DR5 agonist capable of binding and clustering exactly four receptors per molecule. Additionally, INBRX-109 was designed to avoid recognition by pre-existing anti-sdAb antibodies commonly present in humans. In preclinical testing, DR5 signaling activated programmed cell death has been observed to be directly proportionally to the number of DR5 molecules clustered. We believe INBRX-109 has the potential to show clinical activity across 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 data from the Phase 1 dose escalation portion of this trial in the first half of 2019, and treatment cohort efficacy data in the middle of 2020.