Relief Therapeutics Holding AG (RLFTF)

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SIX INDICATIONS WITH TWO BIOMARKERS???

In the coming year, we intend to initiate clinical trials for the following indications:

1- COVID “longhauler” syndrome: millions of Americans continue to suffer from reduced respiratory capacity and require home oxygen in order to maintain adequate blood oxygen levels.

2- Sarcoidosis: this chronic lung disease affects 185,000 Americans and causes pulmonary disability and death in 1% to 5% of those affected. The FDA has recognized Sarcoidosis as an orphan disease.
3- Acute Respiratory Distress Syndrome (ARDS): this is the condition that Prof. Sami Said first treated in the last years of his career, together with our Principal Investigator, Dr. J. Georges Youssef of Houston Methodist Hospital. Seven of the 8 patients they treated at Stonybrook University Hospital survived the Intensive Care Unit and 6 successfully left the hospital.

4- Checkpoint inhibitor pneumonitis: one of the most promising developments in cancer chemotherapy is the advent of checkpoint inhibitor drugs, of which Keytruda® (pembrolizumab) is the best-known example. While these drugs have shown promise in previously hopeless malignancies, they cause a highly unpleasant lung inflammation (pneumonitis) that is a challenge for patients and their families. There are reports in the medical literature of substantial relief being achieved with inhaled aviptadil.

5- Preservation of donor lungs both before and after transplant: There is a substantial pre-clinical literature on the effect of aviptadil in protecting donor lungs both while outside the body and after transplant. Dr. Youssef has treated some lung transplant patients under an investigator-sponsored IND with encouraging results.

6- Chronic Obstructive Pulmonary Disease (COPD): Highly provocative data have been shared with us regarding the potential for aviptadil to improve symptoms in patients with advanced COPD. More than 15 million Americans suffer from COPD and treatment at this time is largely confined to custom-compounded off-label use of inhaled steroids and bronchodilators. Our manufacturing partner, Nephron Pharmaceuticals, is one of the nation’s largest suppliers of custom inhaled medicines.

Thus, we have lots of work to do and many millions of patients who may require ZYESAMI. We are working with Mannkind (Nasdaq:MNKD) to adapt their dry powder insulin delivery system to deliver inhaled aviptadil in order to achieve a room-temperature stable, convenient to use medicine. We are also working with TFF Pharmaceuticals (Nasdaq:TFFP) to develop a long-term stable reconstitutable form of ZYESAMI.

Investors ask us on a daily basis when the FDA will grant EUA to ZYESAMI for the treatment of Critical COVID-19. As you know, the FDA wrote to us in December 2020 and advised that they required randomized prospective data to consider granting EUA. Dr. Peter Stein of the FDA stated that the FDA remained committed to working with us on our investigational medicine and advised us that the FDA would review any submission of randomized prospective data “promptly.” Although there is no statutorily mandated period within which the FDA must make a determination on EUA, the project manager who is supervising our EUA application advised us on Friday, October 1, that the review is ongoing and that the FDA is awaiting input from some members of its staff.

In the course of developing randomized prospective data in support of the EUA, we believe that we have fulfilled the requirements for Breakthrough Therapy Designation and have submitted that application to the FDA. We may also meet the legal requirements for accelerated approval under section 506c of the Food, Drug, and Cosmetics Act, based upon the findings in two separate trials demonstrating a statistically-significant response on two biomarkers: Respiratory Distress Ratio and Cytokine IL-6.

The statute states that the FDA may grant accelerated approval to:

. . . a product for a serious or life-threatening disease or condition . . . upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

As you know, ZYESAMI is one of three products in our pipeline with potential for approval in 2022, the other two being NRX-101 and the BriLife vaccine. Each product has the potential to save countless lives and to generate significant value for shareholders. We will provide updates about BriLife and NRX-101 in future communications.

On behalf of the entire NRx team, we thank you for placing your trust in us as we work tirelessly to improve patients’ health and save lives. We look forward to sharing further results in the coming months.

Best Regards,

Jonathan C. Javitt, MD, MPH
Chairman and CEO of NRx Pharmaceuticals

Cautionary Note Regarding Forward-Looking Statements

This statement of NRx Pharmaceuticals, Inc. includes “forward-looking statements” within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995, which may include, but are not limited to, statements regarding our financial outlook, product development, business prospects, and market and industry trends and conditions, as well as the company’s strategies, plans, objectives, and goals. These forward-looking statements are based on current beliefs, expectations, estimates, forecasts, and projections of, as well as assumptions made by, and information currently available to, the company’s management. The company assumes no obligation to revise any forward-looking statement, whether as a result of new information, future events or otherwise. Accordingly, you should not place reliance on any forward-looking statement, and all forward-looking statements are herein qualified by reference to the cautionary statements set forth above.

WHAT IS ACCELERATED APPROVAL PATHWAY???

The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. ... If the drug later proves unable to demonstrate clinical benefit to patients, the FDA may withdraw approval. ~ Wiki

WHAT IS THE BIGGEST DIFFERENCE BETWEEN STANDARD APPROVAL OF A NEW DRUG APPLICATION AND ACCELERATED APPROVAL???

The difference is that drugs granted accelerated approval must promptly conduct post-marketing confirmatory trials to verify the clinical benefit (as early as underway at the time the marketing application is submitted…Pharmaceutical Development Group

WHAT ARE ACCELERATED CLINICAL TRIALS???

Introduced in 1992 and modified in 2012, accelerated approval allows the FDA to base approval of drugs for “serious conditions that fill an unmet medical need on whether the drug has an effect on a surrogate or an intermediate clinical endpoint.” In other words, marketing approval can be based on clinical trials that do not yet show an improvement of a definitive endpoint such as increased longevity, reduction in the incidence of heart attacks or healing of an infection.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690300/

WHEN CAN YOU ASK FOR ACCELERATED APPROVAL???

Accelerated approval is used when a disease course is long and measuring the clinical benefit would require significant time.

https://www.definitivehc.com/resources/glossary/accelerated-approval