To view all documents filed with the SIX Swiss Exchange, please visit the “Notices Market Participants” section of ser-ag.com aand select RELIEF THERAPEUTICS Holding AG in the Issuer filter.

We publish our half year and annual results in compliance with SIX requirements. Typically, this occurs in April and September of each fiscal year, respectively.

Relief’s management team strategy is to maintain a lean internal structure and a series of collaborations with relevant worldwide experts. Our management team works collectively to execute all duties traditionally assigned to a CEO. In 2020 and early 2021, Relief added senior executives with extensive experience in finance, commercialization, medical, clinical development and manufacturing, and we plan to continue to add expertise by hiring personnel and consultants in an effort to match the Company’s pace of development.

On January 21, 2021, Relief announced the implementation of a new Share Subscription Facility ("SSF") in the amount of up to CHF 50 million with the Company’s main shareholder GEM Global Yield LLC SCS.

Under the terms of the SSF, Relief has the right to periodically, during a timeframe of up to three years, issue and sell shares to GEM. Under the facility, GEM undertakes to subscribe to or acquire ordinary registered RELIEF THERAPEUTICS Holding AG shares upon Relief's exercise of a draw down notice. In accordance with the customary terms of the SSF agreement, Relief will control the timing and maximum amount of any draw down, and retains the right, not the obligation, to draw down on the full commitment amount.

As of March 31, 2021, no funds have been drawn down from the current SSF agreement.

Scientific publications on RLF-100™ can be view here: https://relieftherapeutics.com/pipeline..

We cannot speculate on the likelihood or timing of FDA approvals. In March 2021, Relief’s partner NeuroRx reported top-line 60-day results from the phase 2b/3 clinical trial in critical COVID-19 patients with respiratory failure. According to NeuroRx, across all patients and sites, RLF-100™ IV met the primary endpoint for successful recovery from respiratory failure at days 28 and 60 and also demonstrated a meaningful benefit in survival after controlling for ventilation status and treatment site. On the basis of these findings, in May 2021, NRx Pharmaceuticals, Inc. (now the parent of NeuroRx) submitted an application to the FDA for Emergency Use Authorization (EUA). NeuroRx subsequently plans to submit a New Drug Application (NDA) to the FDA based on these top-line results and including full chemistry, manufacturing and controls (CMC) data as well as additional information on the profile of the drug from other previously conducted clinical and preclinical studies. The FDA granted RLF-100™ Fast Track designation in June 2020, which, among other things, makes RLF-100™ eligible for Priority Review if relevant criteria are met. Priority Review designation means the FDA’s goal is to take action on an application within 6 months compared to 10 months under standard review. It would be reasonable to expect Priority Review for applications filed under the Coronavirus Treatment Acceleration Program (CTAP). RLF-100™ is part of this program, which was promulgated by the FDA in 2020 in express response to the emergence of the COVID-19 pandemic.

The U.S. phase 2/3 study with the inhaled formulation of RLF-100™ was initiated by NeuroRx, Inc. in February 2021. According to clinicaltrials.gov, study completion is estimated in December 2021.

Relief holds a patent covering potential formulations of RLF-100™ in the United States valid until at least July 2029, with extension opportunities up to five years as well as in the EU and Rest of World (Great Britain, Germany, Turkey, Spain, Switzerland, Netherlands, Denmark, Ireland, Austria, PRC and Mexico) valid until at least 2026, excluding extension opportunities comparable to the U.S. In part to further build the IP portfolio, Relief and AdVita Lifescience GmbH signed a binding term sheet in January 2021 for Relief to acquire all shares of AdVita. Relief will gain access to all AdVita assets including future pending IP rights that may cover RLF-100™ inhaled formulation specifications for the potential application of inhaled aviptadil in the treatment of lung diseases such as ARDS and pulmonary sarcoidosis.

In March 2021, NeuroRx reported top-line 60-day results from the phase 2b/3 clinical trial in critical COVID-19 patients with respiratory failure. According to NeuroRx, across all patients and sites, RLF-100™ IV met the primary endpoint for successful recovery from respiratory failure at days 28 and 60 and also demonstrated a meaningful benefit in survival after controlling for ventilation status and treatment site. On the basis of these findings, in May 2021, NRx submitted an application to the FDA for EUA. Relief cannot speculate on the timing of a decision by the FDA but will report this information when known.

Relief is currently preparing a European phase 2b/3 study with RLF-100™ in COVID-19-induced acute respiratory distress syndrome (“ARDS”) patients. Once the EUA application is submitted and the FDA makes a decision, Relief will decide on the best path forward for the development of RLF-100™ IV in Europe and other territories. It is our hope that, should the FDA grant EUA for RLF-100™, this could expedite the clinical assessment of RLF-100™ in Europe. For this reason, a European trial with RLF-100™ IV would not commence until a decision on EUA has been announced.

In April 2021, Relief announced the initiation of a phase 2 trial evaluating the inhaled formulation of RLF-100™ for the prevention of COVID-19-related ARDS. The study, Inhaled Aviptadil for the Prevention of COVID-19 Related ARDS (NCT04536350), is a randomized, double-blind, placebo-controlled phase 2 investigator-sponsored trial being conducted at several clinical sites in Switzerland. It is estimated that the study will take approximately 6-12 months to complete, depending on the progression of the ongoing COVID-19 pandemic.

Additional clinical trials evaluating RLF-100™ are underway or planned. Please see the Pipeline-RLF-100™ (aviptadil) section of the website for details.

A pre-NDA meeting between Acer and the FDA was completed in the second quarter of 2021. In August 2021, Relief and Acer announced the submission of the NDA to the FDA under the 505(b)(2) pathway for ACER-001 in UCDs. In October 2021, the FDA accepted the NDA for the treatment of patients with UCDs and assigned a PDUFA target action date of June 5, 2022.