Set to begin in the third quarter of 2017, the collaboration will cover the safety, tolerability, and effectiveness of a small-molecule MNK1/2 inhibitor called eFT508 in a randomized Phase 2 clinical trial. The trial will examine eFT508 as a stand-alone therapy and in combination with Bavencio (avelumab). Twice as many participants will receive the combo as eFT508 alone.
“We believe eFT508, our lead program, is a promising new immuno-oncology drug candidate that could significantly improve patient response in combination with checkpoint inhibitors,” Dr. Steve Worland, president and CEO of eFFECTOR, said in a press release. “We are very pleased to be working with Pfizer and Merck KGaA, Darmstadt, Germany, given their demonstrated commitment to develop avelumab as a leading checkpoint inhibitor and their deep knowledge in the field of immuno-oncology.”
Immunotherapeutics, such as eFT508 and Bavencio, combat cancer by harnessing the body’s immune system.
EFT508 is an oral immunotherapy that inhibits MNK1/2 kinases, which help tumors evade the immune system. Blocking these kinases could allow the immune system to recognize tumor cells and fight them.
Experiments have shown that eFT508 can activate anti-cancer responses by decreasing a tumor’s ability to suppress the immune system. Researchers did this by inhibiting proteins involved in this mechanism, including PD-1, LAG3, PD-L1, and IL-10.
EFT508 boosts the immune system in a number of ways, including activating immune T-cells and dendritic cells.
Bavencio, a checkpoint inhibitor, is an antibody that blocks protein programmed death ligand-1, or PD-L1. Tumors cells produce PD-L1, which binds to the PD-1 receptor on the surface of immune cells, hampering their activity. Blocking PD-L1 helps the immune system recognize the presence of tumor cells, and work to kill them.
EFT508 worked by itself and in combination with other drugs to generate anti-tumor activity in animals with compromised immunity, according to preclinical-trial studies. That was particularly true when the other drugs were checkpoint inhibitors.
“EFFECTOR’s approach in targeting selective translation regulators is unique, and eFT508 represents a promising novel class of investigational compounds for the treatment of cancer,” said Dr. Chris Boshoff, a senior vice president at Pfizer Global Product Development. “Given the preclinical data already developed with eFT508 and checkpoint inhibitors, we are excited to initiate this joint clinical collaboration.”
“Colorectal cancer is a frequently diagnosed cancer and is the second most common cause of cancer death among men and women combined” in the United States, said Alise Reicin, head of Global Clinical Development at Merck Darmstadt’s biopharma business. “New and innovative treatment strategies are desperately needed. We look forward to exploring the potential of this novel combination and the role we hope it may eventually have for improving the treatment of colorectal cancer.”
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