March 26, 2020
RELIEF THERAPEUTICS Holding AG (SIX:RLF) “Relief”, together with NeuroRx, a Delaware Corporation. have filed an Investigational New Drug (IND) Application with the US FDA for a phase 2 trial of RLF-100 (Aviptadil) in the treatment of Acute and Moderate Respiratory Distress in patients infected by the COVID-19 coronavirus. NeuroRx, Inc. is a privately held, drug development company that has previously demonstrated success in developing innovative drugs under FDA Fast Track, Breakthrough Therapy, and Special Protocol Agreement programs. Relief previously partnered with Biogen (Nasdaq:BIIB) to develop Aviptadil for the treatment of pulmonary hypertension.
“In a previous trial of VIP for ARDS caused by sepsis, 7 of 8 patients on mechanical ventilation showed substantial improvement and 6 ultimately left the hospital alive,” said Prof. Jonathan Javitt, MD, MPH, the CEO of NeuroRx, Inc. and Vice Chairman nominee of Relief. “Patients on ventilators for COVID-19 have only a 50% chance of survival and if the early results can be replicated in ARDS caused by COVID-19, this treatment could have a major impact both on COVID-19 survival and on the availability of ventilators for those in desperate need. Should this trial demonstrate efficacy, Relief Therapeutics has sufficient immediately shippable drug substance to treat more than 100,000 Americans.”
Death in COVID-19-infected patients is caused by a “cytokine storm” in the lungs, in which the virus triggers inflammatory molecules called “cytokines,” which cause the air sacs (alveolae) of the lungs to fill with water and become impermeable to oxygen, even in the setting of mechanical ventilation. VIP is a naturally synthesized peptide which is 40% concentrated in the lungs and which has been shown to have a potent anti-cytokine activity in numerous animal models of respiratory distress, acute lung injury, and inflammation. It has a 20-year history of safe use in human beings in multiple human trials for sarcoidosis, pulmonary fibrosis, and pulmonary hypertension, and is marketed in Europe as a local injection to treat erectile dysfunction. At an FDA public hearing in 2016, it was noted that more than 8,000 prescriptions for VIP were filled by a compounding pharmacy to treat a chronic inflammatory condition without any reported adverse events.
Relief Therapeutics holds FDA and EU orphan drug designations for the use of VIP to treat ARDS, pulmonary hypertension, and sarcoidosis. Relief also holds a US patent for Aviptadil and proprietary manufacturing processes for its synthesis.
“Humanity is threatened by a deadly virus that has demonstrated a propensity to cause lethal ARDS. Conventional forms for respiratory support have so far failed to preserve life in half of those who develop ARDS in the setting of COVID-19 infection,” commented Dr. Raghuram (Ram) Selvaraju, PhD, MBA, Chairman of Relief. “We are cautiously optimistic that the early observations wherein RLF-100 7 of 8 patients with sepsis-related ARDS will carry over to today’s crisis.”
The Relief group of companies focus primarily on clinical-stage projects based on molecules of natural origin (peptides and proteins) with a history of clinical testing and use in human patients or a strong scientific rational. Currently, Relief is concentrating its efforts on developing new treatments for respiratory disease indications.
Founded in 2015, NeuroRx was established to develop N-methyl-D-aspartate (NMDA) receptor antagonist drugs, initially targeting CNS indications related to treatment of suicidal depression and PTSD. It is also known that lung inflammation is NMDA-mediated. The Company has demonstrated substantial capacity for efficient drug development that follows the pathways enabled by the 21st Century Cures Act, passed by the US Congress in 2016. Those pathways include Fast-Track and Breakthrough Therapy Designations, Special Protocol Agreements, and Biomarker-based drug development. NeuroRx is led by Prof. Jonathan Javitt, MD, MPH, Senior Fellow of the National Security Health Policy Center of the Potomac Institute and former Special Employee of the Undersecretary of Defense. The Company’s board of directors and advisors includes Hon Sherry Glied, former Assistant Secretary for Health, Daniel Troy, JD, former Chief Counsel of the US FDA, Wayne Pines, Former Associate Commissioner of the US FDA, and General HR McMaster, the 23rd National Security Advisor.
RLF-100 (Aviptadil) is a patented formulation of Vasoactive Intestinal Polypeptide (VIP) that was originally developed and is currently marketed in Europe for the treatment of erectile dysfunction. VIP is known to be highly concentrated in the lung and to inhibit a variety of inflammatory cytokines. Aviptadil was awarded Orphan Drug Designation in 2001 by the US FDA for treatment of Acute Respiratory Distress Syndrome and in 2005 for treatment of Pulmonary Arterial Hypertension. Aviptadil was awarded Orphan Drug Designation by the European Medicines Agency in 2006 for the treatment of Acute Lung Injury and in 2007 for the treatment of Sarcoidosis. Both the US FDA and the EMEA have granted Investigational New Drug licenses for human trials of Aviptadil.
Acute respiratory distress syndrome (ARDS) is a form of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath, rapid breathing, and bluish skin coloration. Among those who survive, a decreased quality of life is relatively common.
Causes may include viral infection, sepsis, pancreatitis, trauma, pneumonia, and aspiration. The underlying mechanism involves diffuse injury to cells which form the barrier of the microscopic air sacs of the lungs, surfactant dysfunction, activation of the immune system, and dysfunction of the body’s regulation of blood clotting. In effect, ARDS impairs the lungs’ ability to exchange oxygen and carbon dioxide.
The primary treatment involves mechanical ventilation together with treatments directed at the underlying cause. Ventilation strategies include using low volumes and low pressures. If oxygenation remains insufficient, lung recruitment maneuvers and neuromuscular blockers may be used. The syndrome is associated with a death rate between 35 and 50%.
Globally, ARDS affects more than 3 million people a year.
RELIEF THERAPEUTICS Holding AG is listed on the SIX Swiss Exchange under the symbol RLF.
This communication expressly or implicitly contains certain forward-looking statements concerning RELIEF THERAPEUTICS Holding AG, NeuroRx, Inc. and their businesses. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of RELIEF THERAPEUTICS Holding AG and/or NeuroRx, Inc. to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. RELIEF THERAPEUTICS Holding AG is providing this communication as of this date and does not undertake to update any forward looking statements contained herein as a result of new information, future events or otherwise.
 Pending election at the upcoming General Assembly of Relief Shareholders
 FDA Pharmacy Compounding Advisory Committee, November 3, 2016
 US 8,178,489 Formulation for Aviptadil