To Our Shareholders,
We have received many inquiries from shareholders following the recent encouraging news regarding Merck’s Molnupiravir results in early COVID-19. We have also received various questions about the status of our application to the US Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) for ZYESAMI.
Needless to say, we are extremely encouraged by the news of the early stopping of recruitment into Merck’s clinical trial on the basis of overwhelming efficacy in treating patients with newly diagnosed COVID-19. The 50% reduction in risk of hospitalization or death among patients in the early viral phase of the disease is some of the best news that has been seen in this phase of the disease since the outbreak of the pandemic. It’s critical to remember, however, that antiviral drugs work primarily in the earliest stage of the disease when the SARS-CoV-2 virus is actively propagating throughout the body.
Investors have asked us for guidance regarding the potential effect of this development on the need for aviptadil to treat the lungs of patients who contract COVID-19. Unfortunately, we believe that patients will continue to need a drug that protects the lining of the lung for the foreseeable future. With over 110,000 new cases of COVID per day in the US alone, and nearly 2,000 COVID-19 deaths reported each day in the US alone, reducing hospitalization from 14,000 to 7,000 new cases each day still leaves several million patients in the US who desperately need a medicine that can help them return to their families.
While we hope that the addressable market for ZYESAMI™ (aviptadil) will be reduced by a lower incidence of respiratory failure in COVID-19, we anticipate that patients in the ICU with respiratory failure with COVID and other conditions will benefit from ZYESAMI for the foreseeable future. Indeed, we have always anticipated and advised investors that should ZYESAMI be deemed safe and effective, it is likely to be used as part of a cocktail in the manner that HIV is treated today. As you know, the NIH is currently conducting a study of ZYESAMI plus remdesivir. Now that Molnupiravir has shown efficacy, we hope that NIH will consider a similar combination trial. Those who attended the FDA/NIH COVID-19 workshop heard Dr. Francis Collins speak about ACTIV3-b. He identified ZYESAMI as one of the few remaining viable treatment options from among the 750 screened by the NIH. In fact, ZYESAMI is the only drug to our knowledge currently being tested by the NIH in the most critically ill patients, those on ventilators.
Were COVID to disappear tomorrow, which we view as highly unlikely, ZYESAMI has many critically important treatment opportunities that we aim to address in the coming year. FDA offered public testimony in 2016 that the safety and efficacy of aviptadil were unknown because there was no pre-clinical or clinical safety data on file with FDA. Over the past year, we have assembled a complete Investigational New Drug (IND) file, and FDA has advised us in writing that no additional, non-clinical toxicity data are needed in order to file a New Drug Application (NDA). This foundation enables the study of important additional indications for ZYESAMI.
In the coming year, we intend to initiate clinical trials for the following indications:
- COVID “long hauler” syndrome: millions of Americans continue to suffer from reduced respiratory capacity and require home oxygen in order to maintain adequate blood oxygen levels.
- 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.
- 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 eight patients they treated at Stonybrook University Hospital survived the Intensive Care Unit, and six successfully left the hospital.
- 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.
- Preservation of donor lungs both before and after transplant: There is 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.
- 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 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 US 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.
