RELIEF THERAPEUTICS Holding AG (SIX:RLF) “Relief” and its U.S. partner, NeuroRx, Inc. today announced that Houston Methodist Hospital is participating in their Phase 2 clinical trial evaluating RLF-100 as a research intervention for critically ill patients with COVID-19 and respiratory failure. RLF-100 is a patented formulation of Aviptadil, (synthetic human vasoactive intestinal polypeptide or VIP), which targets alveolar type 2 cells in the lungs that are a major target of the SARS-CoV-2 virus. VIP is known from numerous animal models of lung injury and lung disease to inhibit inflammatory cytokines and to protect pulmonary epithelial cells that line the air sacs (alveolae) of the lungs.

The multicenter clinical trial will enroll patients with COVID-19 and respiratory failure in the hopes that RLF-100 can decrease mortality in this condition and help to improve the ability of the patient’s lungs to transfer oxygen to the body. Based on recent FDA guidance, the trial has been expanded to include patients treated with high flow nasal oxygen and noninvasive forms of ventilation, instead of only enrolling patients on mechanical ventilators.

The Principal Investigator at Houston Methodist Hospital is J. George Youssef, M.D., assistant professor of Critical Care Medicine & Pulmonology. Dr. Youssef was a co-investigator in the earlier study evaluating RLF-100 as a treatment for Acute Respiratory Distress (ARDS), a primary cause of COVID-19 related deaths, under the late Professor Sami Said, who discovered VIP in 1970 and treated the first patients.

“We are encouraged by findings from the previous clinical trial of RLF-100 as a treatment for ARDS in patients with sepsis which showed seven out of eight patients on mechanical ventilation experienced substantial improvement and six ultimately left the hospital alive,” Dr. Youssef said. “If the early ARDS results can be replicated in critically ill COVID-19 patients with respiratory failure, this approach could present a significant advancement in the treatment of these patients.”

Jonathan Javitt, M.D., MPH, CEO of NeuroRx, added, “We at NeuroRx are enormously excited to have Dr. Youssef join our study, in light of his long involvement in the VIP story. While we can read about Dr. Said’s breakthrough, Dr. Youssef witnessed it firsthand and participated in the early clinical care of patients. It’s rare to have science come full circle in service of patients.”

The trial is being led by NeuroRx, Inc., the US development partner of Relief Therapeutics, whose clinical operations are based in Radnor, PA. Patients are being treated under an FDA Investigational New Drug clearance, as part of the FDA’s Corona Treatment Acceleration Program (CTAP). Details of the study are posted on clinicaltrials.gov NCT04311697.

About VIP in Lung Injury

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, that is critical to transmission of oxygen to the body. VIP has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, pulmonary fibrosis, asthma/allergy and pulmonary hypertension.

COVID-19-related deaths are primarily caused by Respiratory Failure. Before an acute deterioration in lung function, there is evidence of early viral infection of the alveolar type 2 cells. These cells are known to have angiotensin converting enzyme 2 (ACE2) receptors at high levels, which serve as the route of entry for the SARS-CoV-2 into the cells. Coronaviruses are shown to replicate in alveolar type 2 cells, but not in the more numerous type 1 cells.1,2 Since type 2 alveolar cells have high concentrations of VIP receptors on their cell surfaces, the research hypothesis is VIP administration could specifically protect these cells from injury.

Injury to the type 2 alveolar cells is an increasingly plausible mechanism of COVID-19 disease progression.3 These specialized cells replenish the more common type 1 cells that line the lungs. More importantly, type 2 cells manufacture surfactant that coats the lung and are essential for oxygen exchange. Other than RLF-100, no currently proposed treatments for COVID-19 specifically target these vulnerable type 2 cells.