SAN DIEGO, April 16, 2018 – eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulators (STRs) for the treatment of cancer, today announced a podium presentation on the structure and discovery of eFT226, a novel, potent and selective small molecule inhibitor of eukaryotic initiation factor 4A (eIF4A) at the American Association for Cancer Research (AACR) Annual Meeting held in Chicago this week. eIF4A is a RNA helicase that regulates the expression of important oncogenes and tumor survival factors. Later in the meeting eFFECTOR will present two posters further describing the role of MNK1/2, the target of the company’s lead asset eFT508, in immune cell signaling, as well as the beneficial effects of eFT508 on enhancement of memory T cell pools, prevention of T cell exhaustion and reprograming of T cell signaling networks.
“eFT226 was discovered through eFFECTOR’s medicinal chemistry discovery platform, leveraging sophisticated computational methods to correlate potency with properties of the drug candidate,” said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. “Because eFT226 inhibits expression of several key oncogenes simultaneously, we look forward to exploring its potential in a dose escalation study to be initiated in the second half of 2018 in patients with B cell lymphomas.”
Siegfried Reich, Ph.D., senior vice president of research and a co-founder of eFFECTOR, gave the podium presentation on the structure and discovery of eFT226, titled “eFT226: A Selective and Highly Potent Inhibitor of Eukaryotic Initiation Factor 4A (eIF4A), A Novel Approach for the Treatment of Cancer,” during the New Drugs on the Horizon 2 session. eFT226 is a novel, potent and selective small molecule inhibitor of the eIF4A RNA helicase that was designed using ligand-based computational methods coupled with small molecule crystal structure analysis. eIF4A is an essential regulator of translation that drives the expression of important oncogenes and survival factors including Myc, Mcl1, Cdk4/6, CycD and beta-catenin. Dr. Reich described the novel binding mode for this class of compounds which leads to the formation of a sequence-specific ternary complex between eFT226, eIF4A and mRNA, resulting in translational repression of key oncogenic drivers of tumor growth. eFT226 demonstrates potent in vivo efficacy in tumor models, which supports advancement of eFT226 into clinical development, initially in patients with B cell lymphomas.
eFFECTOR scientists will also present two posters further characterizing the immuno-oncology activity of eFT508, the company’s lead compound in Phase 2 clinical development. The first poster, titled “eFT508, a potent and highly selective inhibitor of MNK1 and MNK2, regulates T cell differentiation promoting an antitumor immune response” presents data demonstrating eFT508’s activity at multiple steps in the cancer immunity cycle including expansion of memory T cells, prevention of T cell exhaustion and shifting the distribution of T cells towards a central memory phenotype leading to a more persistent immune response in vivo. The second poster, titled “Inhibition of MNK by eFT508 reprograms T cell signaling to promote an anti-tumor immune response,” reveals that eFT508 inhibition of MNK1/2 selectively controls the translation of key regulators of the anti-tumor immune response and enhances T cell function through selective modulation of T cell signaling networks that regulate aspects of mRNA translation, mRNA stability, and mRNA splicing.
“These studies further illustrate that eFT508 enhances anti-tumor immune response by regulating expression of multiple factors that promote T cell function,” added Dr. Worland. “This work has laid the foundation for our broad Phase 2 program for eFT508, including a trial already underway in colorectal cancer in combination with Pfizer’s avelumab, and three additional Phase 2 studies expected to be initiated by the end of this year.”
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.