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. The management team works collectively to execute all duties traditionally assigned to a CEO. Since 2020, Relief has added senior executives with extensive experience in finance, commercialization, medical affairs, clinical development and manufacturing. The company plans to continue to add expertise by hiring personnel and consultants in an effort to match its pace of development. Relief is planning to name a CEO by-mid 2023 or earlier.

Our shares are listed on the SIX Swiss Exchange under the symbol RLF and are quoted in the U.S. on the OTCQB Market under the symbol RLFTF. Additionally, the Company has a level 1 U.S. ADR traded on the OTCQB under the symbol RLFTD.

Relief's stock is included, among others, in the Swiss Exchange Swiss Performance Index, the MSCI Global Small Cap Index, as well as the SXI Life Sciences and SXI Bio+Medtech indices.

As of June 30, 2022, there were 69,663,197 options and 0 warrants outstanding.

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 July 18, 2022, 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. On the basis of these findings, in May 2021, NRx Pharmaceuticals, Inc. (NRx) (now the parent of NeuroRx) submitted an application to the FDA for Emergency Use Authorization (EUA), which was subsequently declined in November 2021. In January 2022, NRx announced that it had submitted an application to the FDA seeking EUA for the use of aviptadil to treat patients with critical COVID-19 who are at immediate risk of death from respiratory failure despite treatment with approved therapy including remdesivir and who are ineligible for enrollment into the ACTIV-3b NIH-sponsored trial, which was subsequently denied in July 2022. 

The U.S. phase 2/3 study with the inhaled formulation of RLF-100® was initiated by NeuroRx, Inc. in February 2021. In March 2022, NRx announced the study was paused. 

In September 2020, Relief entered into a binding collaboration agreement with NeuroRx (the “Collaboration Agreement”) which established the terms under which both parties would collaborate and assist each other to maximize the commercial value of each parties’ territories related to intravenous and inhaled aviptadil for the treatment of COVID-19 and other related pulmonary conditions. However, based on numerous breaches of the Collaboration Agreement by NeuroRx, in October 2021, Relief filed a lawsuit against NeuroRx and its then CEO, Dr. Jonathan Javitt, for multiple breaches of the Collaboration Agreement. The complaint, among other remedies, seeks damages, an order compelling defendant to comply with multiple provisions of the Collaboration Agreement, and a declaration directing NeuroRx to deliver the entire data set from the Phase 2b/3 clinical trial of intravenously-administering aviptadil to Relief. On January 10, 2022, NeuroRx filed a complaint against Relief alleging that the Company is in breach of the Collaboration Agreement and has thus repudiated and cancelled the Collaboration Agreement. Additionally, NeuroRx’s claims include a count for defamation.

On August 22, 2022, Relief and NRx issued a press release announcing that they had agreed to a tentative settlement of the pending litigation. The parties announced that they had agreed to work collaboratively to finalize the settlement within the next thirty days. Further, the parties announced that they had agreed to stay the litigation for an additional sixty days to allow for the negotiation and execution of the definitive settlement agreement and related terms. There can be no assurance that the parties will successfully complete the proposed settlement.

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. The acquisition of AdVita Lifescience GmbH in July 2021, enabled us to strengthen our intellectual property position with pending intellectual property rights that cover an improved formulation of the inhaled version of RLF-100^® (aviptadil) and its potential application for the treatment of acute respiratory distress syndrome (“ARDS”) unrelated to COVID-19 infection, as well as in other pulmonary disorders, including sarcoidosis, berylliosis and checkpoint inhibitor-induced pneumonitis, for which AdVita has already filed pending patent claims. 

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 Leuppi study) (NCT04536350), which is a randomized, double-blind, placebo-controlled phase 2 investigator-sponsored trial being conducted at several clinical sites in Switzerland. The trial is at an advanced stage of recruitment and is slated to report top-line data later this year (subject to enrollment of eligible patients).

Aviptadil remains a molecule with a well-established mechanism of action and widely documented clinical evidence of biological activity, as well as a favorable human safety and tolerability profile established across two decades of clinical evaluation. As such, Relief believes that the drug merits continued assessment across an array of pulmonary conditions, regardless of whether the drug is ever approved for the treatment of COVID-19. Relief intends to initiate a clinical trial of RLF-100^® in early 2023 in patients with pulmonary sarcoidosis, a chronic, rare and debilitating pulmonary disease for which there are no treatments approved and for which Relief has received Orphan Drug designation from the FDA. Relief plans to explore RLF-100^® in checkpoint inhibitor-induced pneumonitis (CIP), an indication in which Relief’s wholly owned subsidiary, AdVita LifeScience GmbH, obtained method-of-use patent protection for aviptadil in February 2022. Additionally, Relief intends to conduct European proof-of-concept clinical development of RLF-100^® in the treatment of chronic berylliosis, an orphan lung disease for which there are no treatments approved, and that is characterized by severe inflammation of the lungs, coughing and increasing breathlessness (dyspnea). Please see the Pipeline-RLF-100^® (aviptadil) section of the website for details.

ACER-001 is a proprietary powder formulation of sodium phenylbutyrate (NaPB). The formulation is designed to be both taste-masked and immediate release. ACER-001 is being developed using a microencapsulation process for the treatment of various inborn errors of metabolism, including Urea Cycle Disorders (UCDs) and Maple Syrup Urine Disease (MSUD). ACER-001 microparticles consist of a core center, a layer of active drug, and a taste-masking coating that quickly dissolves in the stomach to avoid a bitter taste while still allowing for rapid systemic absorption. ACER-001’s taste-masked formulation is designed to improve the palatability of NaPB and could make it a compelling alternative to existing NaPB-based treatments, as the unpleasant taste associated with NaPB is cited as a major impediment to patient compliance with those treatments.

Scientific publications on ACER-001 can be viewed here:

https://relieftherapeutics.com/pipeline

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. In June 2022, Acer was issued a Complete  Response Letter (CRL) regarding the NDA for ACER-001 for UCD. The CRL stated that the FDA could not approve the NDA for ACER-001 for UCD in its current form due to an incomplete inspection of Acer’s third-party contract packaging manufacturer. The FDA did not cite any other approvability issues in the CRL related to the NDA. In mid-July 2022, Acer resubmitted its NDA for ACER-001 for the treatment of UCD FDA, which was subsequently accepted for review by the FDA in late July 2022. The FDA designated the NDA as a Class 2 resubmission and set a PDUFA target action date of January 15, 2023.

On March 22, 2021, Relief and Acer announced the signing of a Collaboration and License Agreement for the worldwide development and commercialization of ACER-001. Under the terms of the agreement, Acer will receive approximately $10 million in cash upon signing (originally $14 million, which was offset by cancellation of the $4.0 million outstanding balance of the prior loan from Relief to Acer following the signing of an exclusivity Option Agreement in January 2021 and a small amount of accrued interest). In addition, Relief has agreed to pay up to $20 million in U.S. development and commercial launch costs for the Urea Cycle Disorders (UCDs) and Maple Syrup Urine Disease (MSUD) indications. Acer will retain development and commercialization rights in the U.S., Canada, Brazil, Turkey and Japan. The companies will split net profits from Acer’s territories 60:40 in favor of Relief. In addition, Relief has licensed the rights for the rest of the world, where Acer will receive from Relief a 15% royalty on all net sales and other revenues received in Relief’s territories. Acer may also receive a total of $6 million in development milestone payments following the first European (EU) marketing approvals for UCDs and MSUD.