NRX Pharmaceuticals, Inc.

Greetings and welcome to the NRX Pharmaceuticals Full Year 2021 Earnings Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Eric Goldstein, Managing Director, LifeSci Advisors. Thank you. You may begin.

Thank you, operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ from statements made on this call is contained in our periodic reports filed with the SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements. Information presented on this call is contained in the press release issued earlier today and in the company's Form 10-K that we are filing today, which may be accessed from the investor's page of the NRX Pharmaceuticals website. Joining me on today's call from NRX Pharm are Robert Bestoff, Interim Chief Executive Officer and Ira Strasberg, Chief Financial Officer and Treasurer. Robert will provide a summary of the company's progress during the year and recent weeks before turning it over to Ira for a review of the company's financial results. Following their prepared remarks, the management team will address investor questions. I will now turn the call over to Robert.

Thank you, Eric. Good morning, everyone, and thank you for joining us today. It is my pleasure to host today's call as interim CEO. We appreciate your attendance. and look forward to providing you with an overview of the refocus priorities that will guide our activities in 2022. Before beginning the agenda for today's call, I want to take a few moments to speak about the leadership transition we announced on March 8th of this year. My predecessor, Dr. Jonathan Javitt, founded NRX and led the building of a company that developed a pipeline with two Phase III novel therapeutics in areas of very high unmet medical needs. Under his leadership, the NRX culture was and remains patient-centric to mitigate the suffering from COVID-19 and other respiratory diseases to providing those who have bipolar depression and suicidality and New Therapeutic Solutions. Recall that up to 50% of individuals with bipolar disorder attempt suicide over their lifetime or have serious thoughts about suicide. NRX went from an idea to reading out a phase two study and obtaining breakthrough therapy designation and a special protocol agreement for the first drug in development for bipolar depression in patients with acute suicidal ideation and behavior. When the COVID-19 pandemic hit two years ago, the NRX team pivoted and rapidly responded to the pandemic challenge that our country and the whole world are still facing today by initiating an investigational new drug clinical study in critical COVID-19 with Aviptadil. Our team went from concept to dosing our first patient in about 12 weeks which included filing an investigational new drug application, filing a protocol, buying active pharmaceutical ingredients to work with manufacturers and to produce clinical supplies, engaging a contract research organization, and sites. This is representative of the culture that defines us today and one that Jonathan and all of us have enabled. We're focused on patients with high on that needs and we are very hands-on and dedicated to rapid and efficient growth development. Today, the company has two late stage drug candidates that can serve as platforms for numerous indications in the psychiatry and respiratory healthcare space. As our phase three programs progress, we have to think about commercialization, hence, The board decided that my extensive experience in pharmaceutical commercialization would best position FaceAMI and NRX 101 for our next corporate phases. I have been in the pharmaceutical industry since the early 1990s, and my career spans a series of commercial and phased leadership positions both in the U.S. and Europe, as well as strategic marketing assignments for large franchises, specifically in the advancement of pipelines. Global Product Launches and Collaborations with Partners. I have worked for global healthcare companies including Eli Lilly, Wyeth, and Pfizer, and I have been part of NRX since 2016. Our company has a strong leadership team. Joining me in this endeavor and on today's call is Ira Strasberg, our new Chief Financial Officer and Treasurer. Ira has been serving NRX in a financial consulting capacity since August of 2021. His career spans over 30 years, including Deputy Chief Financial Officer at Cantor Fitzgerald, various senior level board and chief financial officer roles, as well as audit and consulting roles at KPMG. Following my prepared remarks, Ira will join the call to provide an overview of our financial results, and then together we will address some of the questions you have kindly submitted. So let's begin. As we announced in our press release earlier today, we have decided to refocus our business priorities on two core areas. The development and approval of the intravenous formulation of Sysami for treatment of critical COVID-19 and other respiratory diseases, and two, the reactivation of a clinical trial development program for our psychiatric portfolio, including NRX-101. Given the complex and rapidly changing geopolitical environment we find ourselves in today, we believe it is prudent to narrow our focus on programs that are principally based in the United States and where we can make the earliest and biggest contributions towards improving patient care. While the COVID-19 situation has improved significantly since the early days of the pandemic, according to the CDC, We're still losing about 500 to 1,000 individuals every day in the U.S. to this virus. So let me start by reviewing some of the results of our prioritization. The most immediate change resulting from this refocusing of our priorities is our decision to not continue the pursuit of the three-life vaccine project of the Israel Institute for Biological Research. This is one area in which geopolitical changes across the world stage have had a significant impact in our perspectives and ability to operate in certain regions. Given the rapidly changing vaccine environment and commercial expectations, we believe the best use of our resources is to focus on Sazami and NRX 101 in the U.S. We're working with our partners in Israel on this transition. SESAMI is our proprietary formulation of aviptadil acetate for the treatment of patients with acute respiratory failure in critical COVID-19 and potentially other respiratory diseases. Intravenous SESAMI is currently being studied in a second Phase III study of patients with critical COVID-19 who are experiencing respiratory failure. The active 3B study is sponsored and managed by the United States National Institute of Health, NIH, In our view, it is a vital study for our country in the fight against COVID-19. Sazami is now the only new investigational treatment drug in this study focus on patients for which there are few alternative therapies, especially once patients are in respiratory failure due to COVID-19. So let's briefly review where we are with Sazami. Recall that in 2021, we completed our Phase 2b3 study of Sysami in critical COVID-19 patients and submitted our first Emergency Use Authorization, or EUA, to the Food and Drug Administration at the end of May 2021. The FDA declined our EUA request in early November of 2021. We also submitted a Breakthrough Therapy Designation, or BTD, request. The FDA denied our request in November One of their comments was that they were denied because Remdesivir is approved for critical COVID-19. Their denial letter gave us insight to re-craft our EUA application, which is the only currently pending regulatory application we have for Sysami. We withdrew our latest BDD application to focus and submit a new EUA application in early February, focused on providing data on patients in our study that had been treated with Remdesivir and continued to progress. Some have heard about some of the recent reports of patients being treated under the Right to Try program and our earlier reports of the experiences with our Expanded Access program. In general, critical COVID-19 patients that are treated earlier in the course of the disease have a better chance of benefiting from Sysami. We thank all the physicians and families who, to date, have chosen to try Sysami under Right to Try or Expanded Access given their loved ones one other alternative when there were no other options for them. Although these experiences are encouraging, I remind us that regulatory actions are based on clinical trial data as per FDA requirements. We also continue to closely track the safety of all patients treated with Saysami, a key area of attention of the FDA. Recall that in their November 2021 reply to our EUA, in a simplified way, the FDA indicated that they needed to better understand the safety profile of SysAmi. To date, about 750 patients have been treated with intravenous SysAmi across the various clinical programs, including our own study, the NIH study, and our expanded access and right-to-try programs. We have not had any new type of serious adverse events It is our view that SESAMI is a drug that can be well used in the ICU or critical care setting. The ongoing NIH active 3B trial is certainly a key study for SESAMI. It is scheduled to enroll 640 patients. NIH recently informed us that about 465 patients have been enrolled in the two Aviptadil arms, Aviptadil alone and Aviptadil plus remdesivir, and the corresponding placebos. Recall that patients are tracked for 90 days. We expect data by the end of the year, notwithstanding Data Safety Monitoring Board reviews, one of which is expected at the end of April. The I-SPI study by the Quantum Leap Health Care Collaborative is an open-label rapid test platform using a Phase II study type approach. In this study, Nebulize Sysami was administered via mouthpiece to 51 mostly critical COVID-19 patients. As we announced this morning, with Quantum Leap in a joint press release, our hope to administer Sysami in a different form to patients may have been hindered by the challenges of administering Nebulize medications to critically ill patients when they're on high flow oxygen of six liters or more. The I-SPI DSMB recently met and recommended stopping their study of inhaled cesamine. Our own inhaled study in severe COVID-19, as opposed to the I-SPI study in critical COVID-19 patients, paused after having enrolled about 40% of the patients. Our DSMB informed us that the study would need to be significantly larger than the original 144 patients targeted. We're evaluating the potential options, including recrafting the enrollment criteria or ending the study to concentrate on the intravenous form of Sysami in the severe and critical patient populations and to explore the use of nebulized Sysami in less severe patient populations and other pulmonary conditions. We continue to believe that Sysami could be a valuable therapeutic for those with COVID-19 respiratory failure who have exhausted all other therapies. As the experience with the Omicron variant demonstrated over the last few months, COVID is likely to remain a persistent, unpredictable, and ongoing health challenge. We continue to believe there will be a need for improved therapeutics to treat severe and critical COVID for some time. To summarize, we see the following potential path for Sysami in 2022. One is our ongoing EUA application for SESAME with a narrower patient population scope, which, as we said earlier, was filed with the FDA in February. There is no statutory prescribed time within which the FDA must respond. The filing of a traditional new drug application or NDA with the FDA for SESAME should the NIH active 3B study support this. With data expected later this year under fast track, we are allowed to initiate submission of parts of our NDA which could accelerate the process if the NIH study is successful. And third, we will also explore the submission for SESAME under the accelerated approval pathway early in the second half of the year. The FDA instituted the accelerated approval program to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint. As previously disclosed, FASAMI showed a series of positive biomarker data, such as IL-6, that correlated with positive outcomes. An NDA will still require studies that confirm that clinical benefit, such as the ACTIV-3B study. As mentioned in prior communication, We have partnerships with Cardinal Health for third-party logistics and distribution services and with Acuvia for commercial and medical pharmacovigilance upon emergency use authorization or NDA approval should we receive that. Now moving to our psychiatry franchise and the development of NRX 101. I am delighted to announce that we are reinitiating clinical development activities in our psychiatry franchise which could result in data within the next 12 to 18 months. This franchise is the starting foundation of our company, and we are in a unique position to help patients in areas of high unmet need. NRX 101 is a patented medicine that should enable patients with bipolar depression and suicidality to be treated on an outpatient basis as an oral, non-addictive medicine. This could allow it to be highly differentiated for the target population. Our NRX 101 clinical plan will have studies for the treatment of bipolar depression with acute suicidal ideation and behavior and for bipolar depression with subacute suicidal ideation and behavior. We are pleased to announce that we're restarting our development efforts in these promising programs. Every year, we lose about 50,000 individuals in the U.S. to suicide. The 50,000 does not include lethal drug overdoses in this population. therefore likely understating the actual number. In the U.S., every year about 150,000 to 180,000 individuals with bipolar depression and acute suicidal ideation and behavior are hospitalized and about two to three times as many have bipolar depression and thoughts of suicide but do not require hospitalization yet. Hence, they have a subacute suicidal ideation and behavior. This represents A very high unmet medical need. It is estimated that 50% of individuals with bipolar disorder attempt suicide in their lifetime and 11 to 20% succumb to suicide. It is these individuals we aim to help with NRX 101. We were awarded breakthrough therapy designation by the FDA for NRX 101 for severe bipolar depression in patients with acute suicidal ideation and behavior, or ASID, after initial stabilization with ketamine or other effective therapy. In the NMDA space, we seem to be the only ones focusing on bipolar depression with suicidality. Recall that antidepressants, including those recently approved for bipolar depression, carry a warning for the increased risk of suicide. So what is on our agenda in our psychiatry franchise for 2022? Being mindful that COVID can disrupt plants. We're pleased to announce that we're currently initiating a phase two clinical study for patients with bipolar depression and subacute suicidality. And just yesterday, on Whale Bipolar Day, we initiated our first study site in this new study. We expect to enroll our first patient in the coming weeks and aim to finish enrollment by the end of this year. We also expect to start a new NRX100 and NRX101 Special Protocol Agreement study for patients with severe bipolar depression and ASIB in the second half of 2022, and we will do so with commercial-level material. This is the study that, if successful, could lead to a new drug application or NDA for NRX101. Of note, restarting this study with commercial-level material will put us in a better position for a potential NDA and commercialization. In summary, we're now focused principally in the U.S. on our two late-stage potentially life-saving drugs, Sasami, delivered intravenously for critical COVID-19 patients, and NRX-101 for bipolar depression in patients with acute suicidal ideation and behavior and subacute suicidal ideation and behavior. Both Phase III studies, if successful, could significantly change patient care in their respective areas. We also see opportunities to leverage both compounds in other populations and disease areas with high unmet needs. With that, I will turn it over to Ira for a brief overview of our financial results.