eFT508 is a novel, potent and highly selective oral small molecule inhibitor of mitogen-activated protein kinase interacting kinases 1 and 2, or collectively, MNK1/2. MNK1/2 play a crucial role in the development of many tumors, including by controlling in a coordinated manner the expression of multiple factors that attenuate an immune response.
The interaction between a patient’s tumor and immune system has been described as a cyclical process referred to as the cancer immunity cycle. Our studies have shown that eFT508 acts on multiple points in the cancer immunity cycle simultaneously, underscoring its therapeutic potential as both a monotherapy and in combination with existing checkpoint inhibitor treatments. Our preclinical studies suggest combining eFT508 with a checkpoint inhibitor can overcome mechanisms of resistance to checkpoint inhibitors, resulting in enhanced sensitivity to checkpoint inhibitors and a higher response rate. In addition, our preclinical data demonstrate that eFT508 as a single agent promotes antitumor immunity that persists after stopping drug treatment.
We have initiated a Phase 2 combination trial of eFT508 with avelumab, an anti-PD-L1 checkpoint inhibitor, in patients with microsatellite stable colorectal cancer (MSS CRC), under a clinical collaboration with Pfizer Inc. and Merck KGaA. We plan to expand our Phase 2 clinical program with a combination trial adding eFT508 treatment to patients already receiving checkpoint inhibitors in FDA-approved indications who are experiencing insufficient response to their checkpoint therapy alone, and a separate combination trial in triple negative breast cancer. Our planned monotherapy trials will include patients with non-germinal center diffuse large B cell lymphoma (non-GCB DLBCL), as well as patients with metastatic castration-resistant prostate cancer (mCRPC).