NeuroRx, Inc. and RELIEF THERAPEUTICS Holding AG  today announced the conclusion of enrollment in the phase 2b/3 trial of ZYESAM (previously RLF-100TM: aviptadil) for the treatment of Respiratory Failure in patients with Critical COVID-19 . No drug-related serious adverse events have been reported as of today. Enrollment was increased from 165 patients in order to amass as large a safety database as possible. Top line data are expected in late January - early February 2021.

"With FDA's authorization and the extraordinary dedication of our twelve clinical trial sites, we were able to take a drug not formulated or administered to patients in IV form since 2005 and advance it to the clinic in ten weeks. We hope that the highly encouraging results seen in the most critically-ill COVID-19 patients treated in our expanded access program can be replicated in patients who have Critical COVID-19 without an advanced comorbidity" said Prof. Jonathan Javitt, CEO and founder of NeuroRx, Inc.

"The FDA did not agree to grant EUA, as applied for in September, based upon the open-label study reported earlier, but has advised us that they remain committed to working with us in the development of our product and will promptly review the forthcoming data from this randomized trial. Until that time, available stocks of ZYESAMITM (RLF-100TM) will continue to be administered under our Expanded Access Protocol and individual patient requests under Right to Try laws."

Raghuram (Ram) Selvaraju, Chairman of the Board of Relief, said: "We congratulate NeuroRx on the successful completion of patient enrollment in this crucial pivotal clinical study and look forward to the top line results. Our fervent hope is for RLF-100TM to bring benefit to critically ill patients suffering the consequences of COVID-19 infection."

About VIP in COVID-19

Vasoactive Intestinal Polypeptide (VIP) was first discovered by the late Dr. Sami Said in 1970. Although first identified in the intestinal tract, VIP is now known to be produced throughout the body and to be primarily concentrated in the lungs. VIP has been shown in more than 100 peer-reviewed studies to have potent anti-inflammatory/anti-cytokine activity in animal models of respiratory distress, acute lung injury, and inflammation. Most importantly, 70% of the VIP in the body is bound to a rare cell in the lung, the alveolar type II cell (ATII), that is critical to transmission of oxygen to the body.

COVID-19-related respiratory failure is caused by selective infection of the ATII cell by the SARS-CoV-2 virus. They are vulnerable because of their (ACE2) surface receptors, which serve as the route of entry for the virus. These specialized cells manufacture surfactant that coats the lung and is essential for oxygen exchange. Loss of surfactant causes collapse of the air sacs (alveolae) in the lung and results in respiratory failure.

VIP is shown to block Coronavirus replication in the ATII cell, block cytokine synthesis, block viral-induced cell death (cytopathy), and upregulate surfactant production. Other than RLF-100™, no currently proposed treatments for COVID-19 specifically target these vulnerable Type II cells