Regulatory T (Treg) cells play a significant role in preventing autoimmune diseases and controlling inflammation. Unfortunately, cancer can co-opt this protective feature of Treg cells to dampen and prevent normal antitumor immune responses.

Human Treg cells express C-C chemokine receptor 4 (CCR4), a receptor protein that plays a key role in the recruitment and accumulation of Treg cells in the tumor microenvironment. FLX475 inhibits the binding of CCR4 to its signaling molecules, blocking the recruitment of Treg cells to the tumor microenvironment. Without excess Treg cells in the tumor microenvironment, the immune system is able to elicit a more robust antitumor response.

Best-in-Class Oral, Small Molecule CCR4 Antagonist

Our lead compound FLX475 is a best-in-class oral, small molecule antagonist of CCR4 for the treatment of cancer. FLX475 is currently in Phase 1 clinical studies in healthy volunteers with a study in patients with cancer scheduled to begin by the end of 2018.

In preclinical efficacy studies, FLX475 demonstrated single-agent efficacy similar to a potent immune agonist. In addition, FLX475 significantly enhanced the antitumor effects of various checkpoint inhibitors including anti-PD-L1 and anti-CTLA4 antibodies as well as immune agonists such as anti-CD137. Both single agent and combination therapies inhibited tumor growth and increased tumor regression. We believe FLX475 has the potential to act alone and to deepen and broaden responses in combination with checkpoint inhibitors. We also expect that FLX475 may be efficacious in combination with CAR-T and cancer vaccine approaches.

Patient Selection Strategy

We will select patients for our clinical studies based on biomarkers and genetic analyses that indicate these patients may be more likely to respond to our small molecule therapeutics. We apply our robust computational and translational biology capabilities to identify key biomarkers that should maximize clinical response and increase the probability of clinical success. For FLX475, we are using a novel development strategy to accelerate early clinical development in cancer patients by first rapidly obtaining pharmacokinetic, pharmacodynamic, and preliminary safety data in healthy volunteers. Findings from the healthy volunteer study will enable a more focused and efficient Phase 1/2 study in cancer patients, which should result in faster achievement of clinical proof-of-concept.

In 2018, we expect to initiate a single agent and combination study of FLX475 in patients with cancer. This study will enroll patients with multiple types of cancer, concentrating on tumor types in which Treg biology plays a significant role including non-small cell lung, triple-negative breast, and head and neck cancers.

In addition, we plan to explore tumors that are associated with the Epstein-Barr Virus (EBV). EBV-associated tumors have increased numbers of Treg in the tumor microenvironment. This elevation of Treg cells has been linked specifically to the biology of both the virus-infected cells which recruit Treg cells, as well as the increase Treg cells expected within the tumor microenvironment . We believe that by selecting EBV+ tumors including nasopharyngeal carcinomas as well as classical Hodgkin’s lymphoma, we have the opportunity to demonstrate meaningful clinical activity leading to an accelerated clinical development path.

* FLX475 is still in development and not yet approved for commercial sale