Relief Therapeutics and NeuroRx has announced topline results from 45 patients assessed in an open-label prospective study where 21 patients admitted to an intensive care unit (ICU) with critical COVID-19 and respiratory failure were treated with RLF-100? (aviptadil) and compared to 24 control patients treated in the same setting. All patients had severe comorbidities that rendered them ineligible for the ongoing randomized controlled phase 2b/3 trial being conducted to ascertain safety and efficacy of RLF-100?, and all patients were deteriorating despite treatment with approved therapies for COVID-19.

Overall, 81% of RLF-100?-treated patients survived beyond 60 days, compared to 17% of control patients. Patients treated with RLF-100? demonstrated a 9-fold increased probability of survival and recovery from respiratory failure, with a high degree of statistical significance. Statistical analysis was performed by Prof. Phil Lavin, FASA, FRAPS of the Boston Biostatistical Research Foundation.

"We are encouraged by these initial results in highly comorbid patients with COVID-19 respiratory failure, and we are pleased that the majority of these patients have returned safely to their families. We look forward to the upcoming results from the randomized, double-blind, prospective trial in less severely comorbid patients for confirmation of these results," said Jihad Georges Youssef, MD, section chief of General Academic Pulmonary Medicine at the Houston Methodist Hospital, who serves as the study's principal investigator at Houston Methodist and also serves as national co-chair for the ongoing randomized controlled trial.

"The patients included in this study are representative of those who are too ill to be included in the clinical trials of any known treatment for COVID-19," said Dr. Jonathan Javitt, CEO and Chairman of NeuroRx, Inc. "We are grateful to Dr. Youssef and to the Houston Methodist Hospital for having the courage to treat and study patients at this level of risk. The results suggest that there may be substantial hope to mitigate the attack of the coronavirus on the delicate cells that line the lung with a natural peptide that has been protecting the lung's lining since humans first walked the earth. While the number of patients treated at Houston Methodist is modest, the initial results in our nationwide expanded access program suggest similarly encouraging survival with RLF-100?. We continue to closely monitor treatment with RLT-100TM in other hospitals."

Scientific findings of the analysis have been submitted for peer review.

Vasoactive Intestinal Polypeptide (VIP) was first discovered by the late Prof. 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 2 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 death is primarily caused by respiratory failure. Before this acute phase, however, 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. These same type 2 alveolar cells have high concentrations of VIP receptors on their cell surfaces giving rise to the hypothesis that VIP could specifically protect these cells from injury.

Injury to the type 2 alveolar cells is an increasingly plausible mechanism of COVID-19 disease progression (Mason 2020). 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.

RLF-100? (aviptadil) is a formulation of Vasoactive Intestinal Polypeptide (VIP) that was developed based on Prof. Sami Said's original work at Stony Brook University, for which Stony Brook was awarded an FDA Orphan Drug Designation in 2001. VIP is known to be highly concentrated in the lungs, where it inhibits coronavirus replication, blocks the formation of inflammatory cytokines, prevents cell death, and upregulates the production of surfactant. FDA has now granted IND authorization for intravenous and inhaled delivery of RLF-100? for the treatment of COVID-19 and awarded Fast Track designation. RLF-100? is being investigated in two placebo-controlled US Phase 2b/3 clinical trials in respiratory deficiency due to COVID-19. Since July 2020, more than 150 patients with Critical COVID-19 and Respiratory Failure have been treated with RLF-100? under FDA-approved protocols.