Preclinical Data Shows Potential of eFT226 in B-cell Malignancies
Data to be presented at the ASH 59th Annual Meeting and Exposition
SAN DIEGO, Dec. 11, 2017 (GLOBE NEWSWIRE) -- eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulators (STRs) for the treatment of cancer, today announced that data presented in a poster session at the American Society of Hematology (ASH) 59th Meeting and Annual Exhibition demonstrate clinical activity, including one partial response, for the company’s lead product candidate, eFT508. In addition, preclinical data presented for another candidate, eFT226, demonstrated the potential for that compound in B-cell malignancies.
Data presented on eFT508 by Ajay K. Gopal, M.D., of University of Washington and Fred Hutchinson Cancer Center, showed that, out of 10 patients treated and evaluable for drug efficacy, one patient with non-germinal center B-cell like diffuse large B cell lymphoma (non-GCB DLBCL) experienced a partial response and remains on therapy, while four additional patients experienced stable disease, including a patient with classical Hodgkins lymphoma who had a marked reduction in tumor volume and also remains on therapy.
“Demonstrating clinical activity in patients participating in this dose-escalation study is highly meaningful to our continued development of eFT508,” said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. “We plan to complete the dose-escalation portion of this study and open an expansion cohort at the recommended Phase 2 dose to evaluate efficacy in patients with non-GCB DLBCL. The work in lymphoma complements our efforts in solid tumors, which includes an ongoing Phase 2 trial of eFT508 in combination with avelumab in patients with microsatellite stable colorectal cancer.”
Patients who experienced either a partial response or stable disease were treated at generally well-tolerated doses in the course of an ongoing dose escalation study. Common treatment related adverse events of fatigue, hypercalcemia, nausea, anemia, gastro-esophageal reflux, tremor, diarrhea and vomiting were generally low grade. One dose limiting toxicity of hypercalcemia and one dose limiting toxicity due to discontinuation during the first cycle of therapy were observed.
The second poster presented the preclinical profile of eFT226, including potent anti-proliferative activity and an induction of apoptosis against a panel of B-cell lymphoma cell lines, as well as selective translational downregulation of a subset of genes that are important for tumor growth and survival.
Dr. Worland added, “In addition, we believe the preclinical data presented for our second compound, eFT226, demonstrate its potential for the treatment of B-cell malignancies and support our plans to initiate a clinical study in lymphoma in the first half of 2018.”
These data were presented at the ASH 59th Annual Meeting and Exposition being held in Atlanta, Georgia on December 9-12, 2017. The posters (#4624 and #1530) are titled “A Phase 1-2 Dose- Escalation and Cohort-Expansion Study of eFT508, a Selective, Orally Bioavailable Inhibitor of MNK1 and MNK2, in Patients with Hematological Malignancies” and “Preclinical Evaluation of eFT226, a Novel, Potent and Selective eIF4A Inhibitor with Anti-Tumor Activity in B-Cell Malignancies.”
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 highly potent and 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 dose escalation study in patients with advanced solid tumors (NCT02605083) and a dose escalation and cohort expansion study in patients with advanced lymphomas (NCT02937675). A Phase 2 study of eFT508 to assess pharmacodynamics markers of immune stimulation in patients with triple negative breast cancer or hepatocellular carcinoma (NCT03318562) is also open for patient recruitment.
eFT226 is a novel, highly potent and selective translation regulator that is an inhibitor of eIF4A1, a RNA helicase and component of the eIF4F translation initiation complex. eFT226 has demonstrated selective inhibition of eIF4A1 driven translation of important tumor oncogenes and survival factors such as c-MYC, CDK4, Cyclin D1/3, β-catenin, BCL2 and MCL-1, blocking tumor cell proliferation and inducing tumor cell death. eFT226 has demonstrated anti-tumor activity in preclinical models of AML, DLBCL, breast, colon and lung cancers. eFT226 is in preclinical development and a Phase 1 study in patients with relapsed/refractory B cell malignancies is planned.