eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulator inhibitors (STRIs) for the treatment of cancer, announced a $5.0 million cooperative agreement sponsored by the Defense Advanced Research Projects Agency (DARPA) and the Defense Health Agency (DHA) to fund a planned Phase 1b study of zotatifin (eFT226) as an anti-viral agent in an outpatient setting for those with mild to moderate COVID-19 disease. The agreement is a subaward of a DARPA research program awarded to the Quantitative Biosciences Institute (QBI) at University of California, San Francisco (UCSF), headed by Brian Shoichet, Ph.D., professor, department of pharmaceutical chemistry, to identify agents active against SARS-CoV-2 infections. eFFECTOR’s efforts will support the Phase 1b clinical study of zotatifin in patients with COVID-19 and related drug development activities.
Zotatifin is an investigational small molecule inhibitor of eukaryotic initiation factor 4A (eIF4A), an enzyme that unwinds complex RNA structures important to producing key disease-driving proteins. SARS-CoV-2 is an RNA virus that hijacks the human cellular machinery—including eIF4A—to replicate. Research led by Nevan Krogan, Ph.D., director of QBI, and the QBI Coronavirus Research Group (QCRG) at UCSF, identified host factor vulnerabilities of SARS-CoV-2 replication published in Nature in April 2020. This research demonstrated that zotatifin was one of the most effective agents in blocking viral replication of SARS-CoV-2 out of 69 compounds evaluated.
“This research agreement allows us to evaluate zotatifin’s antiviral therapeutic potential in non-hospitalized patients suffering from mild to moderate SARS-CoV-2 infections,” said Steve Worland, Ph.D., president and CEO of eFFECTOR. “Zotatifin may have broad utility against a number of coronaviruses, as in vitro studies have demonstrated that it is a potent inhibitor of SARS-CoV-2 and other coronavirus strains, including MERS-CoV.”
Davide Ruggero, Ph.D., professor at the UCSF Helen Diller Cancer Center; an American Cancer Society Research Professor; and co-founder of eFFECTOR, added, “The interdisciplinary approach taken to establish zotatifin’s in vitro activity against SARS-CoV-2, which included proteomics to identify interactions between host and viral proteins and recognition of clinical-stage drug candidates that impacted the identified pathway, exemplifies the broad collaborative efforts taken by QCRG scientists around the world in response to COVID-19.”