FLX475 is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg
) specifically into tumors, but not healthy tissues, without depleting Treg
throughout the body, which we believe may decrease the likelihood of side effects. We are developing FLX475 for the treatment of a broad range of charged tumors, which represent cancer types we believe are most likely to respond to FLX475. In cancer, the secretion of certain chemokines from tumor cells and tumor-resident immune cells is responsible for recruitment of immunosuppressive Treg
to tumor sites. Treg
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 Treg
has the potential to restore 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 have completed a placebo-controlled, double-blinded dose-escalating Phase 1 clinical trial of FLX475 in 104 healthy volunteers. FLX475 was well tolerated and demonstrated dose-dependent inhibition of CCR4 with no observed immune-related adverse events or significant clinical adverse events. We are currently enrolling the Phase 2 portion of a Phase 1/2 study of FLX475 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) encouraging efficacy in combination with the PD-1 checkpoint inhibitor pembrolizumab, (3) biomarker data supporting FLX475’s mechanism of action, and (4) a favorable safety profile both as monotherapy and in combination with pembrolizumab.