INBRX-105

INBRX-105 was developed with our sdAb platform and is both an antagonist of programmed death ligand 1, or PD-L1, and a conditional agonist of 4-1BB. The approval of checkpoint inhibitors that block the interaction between programmed cell death protein 1, or PD-1, and PD-L1 have caused a paradigm shift in oncology treatment, due to their substantial response rates and overall survival benefit across numerous cancers. These therapeutics, however, achieve a lasting benefit only for a minority of patients and therefore additional therapeutic candidates have been tested clinically with the goal of further activating tumor reactive T-cells. These candidates include agonist antibodies targeting 4-1BB, a member of the tumor necrosis factor receptor superfamily (TNFRSF) that has been shown to provide co-stimulatory function to T-cells. While a 4-1BB agonist has shown clinical promise, systemic activation of 4-1BB has led to safety findings that ultimately restricted the dose level administered and, in turn, limited efficacy. To overcome these limitations, we designed INBRX-105 to block the PD-L1/PD-1 interaction and to conditionally agonize 4-1BB in the presence of PD-L1, the expression of which is enriched in the tumor microenvironment and associated lymphoid tissues. We believe this unique mechanism of action has the potential to enhance the anti-tumor response and limit systemic toxicity. INBRX-105 exhibited promising T-cell co-stimulatory activity in preclinical studies by enhancing the activation of antigen specific T-cells to levels in excess of those achieved with a combination of separate PD-L1 and 4-1BB targeting agents. We believe INBRX-105 has the potential to treat patients with PD-L1 expressing tumors, including those that are refractory to or relapsed from approved checkpoint inhibitor therapies. The FDA has accepted the IND for INBRX-105 and we expect to initiate a Phase 1 clinical trial in early 2019.