eFFECTOR Therapeutics Completes Enrollment in Second of Three Cohorts of Phase 1b Clinical Trial of Zotatifin for the Treatment of COVID-19
eFFECTOR Therapeutics, Inc. recently announced it has completed enrollment for the second cohort of a three cohort Phase 1b clinical trial of zotatifin in non-hospitalized adults with confirmed COVID-19 infection. eFFECTOR anticipates opening enrollment in the third cohort by the end of 2022, and expects to report topline data for all three cohorts in the first half of 2023.
The study is a double-blind, randomized, placebo-controlled trial evaluating the safety and antiviral activity of a single dose of zotatifin and is being conducted in collaboration with the Quantitative Biosciences Institute (QBI) at the University of California, San Francisco (UCSF), which holds a $5-million cooperative agreement sponsored by the Defense Advanced Research Projects Agency.
“The rapid enrollment of the second cohort of this trial reflects the continued prevalence of COVID-19, despite the widespread use of vaccines, and it allows us to plan for a topline data readout in the first half of 2023,” said Steve Worland, PhD, President and Chief Executive Officer of eFFECTOR. “As a host-directed antiviral, we believe zotatifin is well-differentiated from agents directed against viral proteins and offers a promising therapeutic option, particularly as a single dose sub-cutaneous injection, both during the current pandemic when new variants are continually a threat, and potentially for other viral diseases.”
Zotatifin is a potent and sequence-selective small molecule inhibitor of eIF4A, a host protein required to unwind the complex secondary structures within the 5’- untranslated region of the genome of SARS-CoV-2 and other RNA viruses. Inhibiting the activity of eIF4A prevents the translation of the viral polyprotein needed for replication of the virus. Zotatifin was identified as a potent anti-SARS-CoV-2 agent in a study conducted by the international research consortium QBI Coronavirus Research Group (QCRG), led by Nevan Krogan, and previously published in Nature.
Zotatifin is an investigational host-directed antiviral, meaning that it acts on a human protein that the SARS-CoV-2 virus hijacks to synthesize new viruses. As such, zotatifin may have a higher barrier to viral mutational escape than therapies that target components of the virus itself.
Zotatifin is a potent and sequence-selective small molecule inhibitor of eIF4A that is designed to suppress expression of a network of cancer driving proteins, including Cyclins D and E, CDKs 2, 4 and 6 and select RTKs as well as KRAS. We are currently investigating zotatifin in ongoing clinical trials for solid tumors and as a potential host-directed antiviral therapy in patients with mild to moderate COVID-19 in collaboration with UCSF.
The Quantitative Biosciences Institute (QBI) is a University of California organized research unit reporting through the UC San Francisco’s School of Pharmacy. QBI fosters collaborations across the biomedical and the physical sciences, seeking quantitative methods to address pressing problems in biology and biomedicine. Motivated by problems of human disease, QBI is committed to investigating fundamental biological mechanisms, because ultimately solutions to many diseases have been revealed by unexpected discoveries in the basic sciences. Learn more at qbi.ucsf.edu.
eFFECTOR is a clinical-stage biopharmaceutical company pioneering the development of a new class of oncology drugs referred to as STRIs. eFFECTOR’s STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase interacting kinase (MNK). The eIF4F complex is a central node where two of the most frequently mutated signaling pathways in cancer, the PI3K-AKT and RAS-MEK pathways, converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. Each of eFFECTOR’s product candidates is designed to act on a single protein that drives the expression of a network of functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival and immune evasion. eFFECTOR’s lead product candidate, tomivosertib, is a MNK inhibitor currently being evaluated in KICKSTART, a randomized, double-blind, placebo-controlled Phase 2b trial of tomivosertib in combination with pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC). Zotatifin, eFFECTOR’s inhibitor of eIF4A, is currently being evaluated in Phase 2a expansion cohorts in certain biomarker-positive solid tumors, including ER+ breast cancer and KRAS-mutant NSCLC. eFFECTOR has a global collaboration with Pfizer to develop inhibitors of a third target, eIF4E. In addition to the company’s oncology focus, zotatifin is being evaluated as a potential host-directed antiviral therapy in patients with mild to moderate COVID-19 in collaboration with UCSF, which holds a $5-million cooperative agreement sponsored by the Defense Advanced Research Projects Agency.
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