Tomivosertib (also known as 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 tomivosertib 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 tomivosertib 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 tomivosertib as a single agent promotes antitumor immunity that persists after stopping drug treatment.
We have two ongoing Phase 2 trials with tomivosertib. The first is a combination trial adding tomivosertib treatment to patients already receiving checkpoint inhibitors in FDA-approved indications who are experiencing insufficient response to their checkpoint therapy alone (CPI-A). The second is a monotherapy trial in patients with metastatic castration-resistant prostate cancer (mCRPC). We also recently entered into a clinical trial collaboration agreement with Merck to combine tomivosertib and Keytruda (PD-1 checkpoing inhibitor) for the treatment of patients with triple negative breast cancer (TNBC).