SAN DIEGO, April 26, 2018 – eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulators (STRs) for the treatment of cancer, today announced that research describing the atom by atom design and biological profile of the company’s lead product candidate eFT508, a potent and highly selective inhibitor of MNK1 and MNK2, has been published in the Journal of Medicinal Chemistry. The peer-reviewed article, which is available online and will appear in today’s print edition of the publication, describes the discovery and characterization of eFT508, which is designed to control translation of mRNA into proteins whose expression is dysregulated in cancer. eFT508 has demonstrated anti-tumor activity in preclinical models of non-germinal center diffuse large B-cell lymphoma and solid tumors.
“This publication showcases our structure-guided drug design expertise that facilitated the design of a potent and highly selective MNK1/2 inhibitor,” said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. “The desirable properties reported in the article enabled us to demonstrate the impact of eFT508 on tumor cell signaling and in vivo tumor growth in preclinical lymphoma models. This research complements our earlier work demonstrating that eFT508 promotes anti-tumor immune response by enhancing antigen presentation, expanding memory T cells, and preventing T cell exhaustion. We are planning a broad Phase 2 program for eFT508, including a trial already underway in microsatellite stable colorectal cancer in combination with avelumab, an anti-PD-L1 checkpoint inhibitor.”
The structure-based design process employed in the design of eFT508 leveraged specific stereoelectronic interactions with the unique active site of the target, resulting in a novel pyridone-aminal structure which provides high potency and selectivity. eFT508’s ability to control dysregulated translation through selective inhibition of MNK1 and MNK2 has the potential to deliver meaningful therapeutic benefit for cancer patients, both as a monotherapy, and in combination with checkpoint inhibitors.
eFT508 is a selective translation regulator and is part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. eFT508 is a potent and highly selective, oral inhibitor of MNK1 and MNK2. MNK1/2 are terminal kinases in key oncogenic signaling pathways, including KRAS-BRAF-MEK-ERK, and are activated by the mitogen-activated protein kinases (MAPK) in multiple immune cell types. MNK1 and MNK2 integrate MAPK pathway signaling at the level of mRNA translation, resulting in decreased anti-tumor immune activity due to selective upregulation of several immune checkpoint receptors and specific immunosuppressive cytokines. eFT508 selectively blocks MNK1/2 driven mRNA translation, thereby promoting anti-tumor immune response. eFT508 is currently being evaluated as a single agent and in combination with avelumab in a Phase 2 clinical trial in patients with microsatellite stable colorectal cancer (NCT03258398), under a clinical collaboration and supply agreement between eFFECTOR and a global strategic alliance of Pfizer and Merck KGaA, Darmstadt, Germany. eFT508 is also being evaluated in a Phase 1 clinical trial in patients with solid tumors (NCT02605083) and in a Phase 1/2 clinical trial in patients with lymphoma (NCT02937675).
About eFFECTOR Therapeutics
eFFECTOR Therapeutics is a clinical-stage biopharmaceutical company focused on pioneering the discovery and development of selective translation regulators as a new class of oncology drugs. The company’s investigational compounds are designed to restore the translational control of processes which tumors have hijacked for their benefit, while preserving normal cell function. eFFECTOR’s most advanced program focuses on the development of eFT508, a MNK1/2 inhibitor in development for the treatment of patients with solid tumors and lymphoma. The company has additional selective translation regulator programs currently in discovery and development and maintains global rights to all of its development programs. For more information visit www.effector.com.
Robert H. Uhl
Heidi Chokeir, Ph.D.