Tivumecirnon: A CCR4 ANTAGONIST THAT COULD UNLOCK AN IMMUNE RESPONSE AGAINST A BROAD RANGE OF “CHARGED" AND VIRALLY ASSOCIATED TUMORS

Tivumecirnon is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (T_reg) specifically into tumors, but not healthy tissues, without depleting T_reg throughout the body. We are developing tivumecirnon for the treatment of a broad range of charged tumors, which represent cancer types we believe are most likely to respond to tivumecirnon. In cancer, the secretion of certain chemokines from tumor cells and tumor-resident immune cells is responsible for recruitment of immunosuppressive T_reg to tumor sites. T_reg represent a dominant pathway for downregulating the immune response, and thus may limit the effectiveness of currently available therapies such as checkpoint inhibitors. Therefore, blocking the migration of T_reg has the potential to reactivate naturally occurring antitumor immunity as well as to synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators and adoptive T cell therapy.

We believe that the inhibition of CCR4 has the potential to bring therapeutic benefit to patients across a wide spectrum of tumors in a manner similar to other immuno-oncology therapies that have been shown to be effective against multiple tumor types, while also potentially deepening or broadening clinical responses to these therapies.

We are currently enrolling the Phase 2 portion of a Phase 1/2 study of tivumecirnon as a monotherapy, and in combination with pembrolizumab, in patients with charged tumors. We reported initial observations from our Phase 1/2 study which included: (1) evidence of monotherapy activity, (2) evidence of activity in combination with the PD-1 checkpoint inhibitor pembrolizumab including in non-small cell lung cancer, (3) biomarker data supporting tivumecirnon’s mechanism of action, and (4) encouraging safety data both as monotherapy and in combination with pembrolizumab.