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• Demonstrated statistically significant anti-tumor activity and inhibited proliferative and stem cell signaling pathways
• Induces beneficial changes in the tumor microenvironment by increasing the production of proteins involved in the interferon-α and interferon-γ pathways
• Proven statistically significant prolongation of survival in combination with carboplatin and everolimus (mTOR inhibitor)
SAN DIEGO, October 07, 2021 (GLOBE NEWSWIRE) – eFFECTOR Therapeutics (NASDAQ: EFTR), a leader in the development of selective translation regulator inhibitors (STRIs) for the treatment of cancer, in collaboration with researchers from Baylor College of Medicine, today announced the presentation of new positive data for zotatifin in animal models of triple negative breast cancer (TNBC) at the AACR-NCI-EORTC 2021 International Conference on Molecular Targets and Cancer Therapeutics. Zotatifin is a potent and sequence-selective inhibitor of translation mediated by eukaryotic translation initiation factor 4A (eIF4A).
The study authors found that blocking eIF4A in p53-null models of breast tumor development in mice with zotatifin leads to tumor control via tumor intrinsic mechanisms as well as to activation of the host’s immune response. This activity is further increased by the addition of chemotherapy. The presentation, entitled “The RNA Helicase EIF4A Is a Therapeutic Vulnerability in Triple Negative Breast Cancer,” was presented by Na Zhao, Ph.D., Postdoc at the Jeffrey Rosen Lab, Department of Molecular and Cellular Biology, Baylor College of Medicine, in an oral session.
“Successful cancer treatments usually require combinations with standard chemotherapy and immunotherapies,” said Jeffrey Rosen, Ph.D., professor, Department of Molecular and Cellular Biology, Baylor College of Medicine. “Resistance is also a major problem that has been observed with individual drugs. We are excited to use the TNBC models developed in our laboratory for these important preclinical studies that we hope will lead into the next generation of clinical trials. “
The story goes on
In the study, treatment with zotatifin slowed tumor growth in six of eight syngeneic TNBC models with no apparent toxicity. Treatment with zotatifin has also been shown to inhibit proliferative and stem cell signaling pathways including E2F targets, G2 / M checkpoints, and NOTCH signaling pathways, and to induce proteins involved in interferon-α and interferon-γ responses . In addition, the combination treatment of zotatifin with the mTOR inhibitor everolimus showed a statistically significantly longer survival time compared to the use of these drugs alone.
“We are pleased to present these very encouraging data through our partnership with researchers at Baylor College of Medicine who are supporting the continued advancement of zotatifin in solid tumor indications, including triple negative breast cancer,” said Steve Worland, Ph.D., President and CEO of eFFECTOR. “We believe that zotatifin may have therapeutic benefits in this difficult-to-treat subgroup of breast cancer patients, especially when combined with other FDA-cleared agents.”
About eFFECTOR Therapeutics
eFFECTOR is a clinical-stage biopharmaceutical company focused on developing a new class of cancer drugs called STRIs. EFFECTOR’s STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase interaction kinase (MNC). The eIF4F complex is a central node where two of the most commonly mutated signaling pathways in cancer, the PI3K-AKT and the RAS-MEK pathways, converge to activate the translation of selected mRNA into proteins that are commonly associated with important disease-causing processes are involved. Each of eFFECTOR’s product candidates is designed to act on a single protein that drives the expression of several functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together support tumor growth, survival and immune evasion steer. EFFECTOR’s lead product candidate, tomivosertib, is an MCA inhibitor currently being investigated in KICKSTART, a randomized, double-blind, placebo-controlled Phase 2b study of tomivosertib in combination with pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC) . Zotatifin, eFFECTOR’s eIF4A inhibitor, is currently being investigated in Phase 2a expansion cohorts in certain biomarker-positive solid tumors, including ER + breast cancer and KRAS mutated NSCLC. eFFECTOR is working with Pfizer worldwide to develop inhibitors of a third target molecule, eIF4E. In addition to the company’s oncology focus, Zotatifin is being used as a potential host-directed antiviral therapy for patients with mild to moderate COVID-19 in partnership with the University of California, San Francisco, under a $ 5 million Defense Advanced Research Projects Agency grant.
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Heidi Chokeir, Ph.D.