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


See how tivumecirnon (FLX475)—designed to block CCR4—may work to potentially treat people with many different types of cancer.


How tivumecirnon works

Tivumecirnon is currently being evaluated in clinical trials.

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Tivumecirnon 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. 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 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 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.

CHARGED TUMORS

Our proprietary discovery engine has identified certain tumors in which the abundance of Treg is likely to be a key cause of immune suppression. We refer to these tumors as “charged” as defined by their expression of high levels of CCR4 ligands, Treg cells and CD8 positive effector cells. These charged tumors include tumor types such as non-small cell lung cancer, head and neck squamous cell carcinoma, gastric cancer and certain lymphomas.

VIRALLY ASSOCIATED TUMORS

Like rogue cancer cells, certain oncogenic viruses such as Epstein-Barr Virus (EBV), may recruit regulatory T cells to evade the immune response. For example, EBV has been shown to directly upregulate the expression of CCL17 and CCL22 in human B cells, making them highly charged with a significantly higher number of regulatory T cells when compared to virally negative tumors.