NRX Pharmaceuticals, Inc.

Good afternoon and welcome to the NRX Pharmaceuticals full year 2022 results conference call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Suzanne Mezuri, Stern Investor Relations. Please go ahead.

Thank you, Danielle. 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 risk. 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 plan to be filed tomorrow, which may be accessed from the Investor Relations section of the NRX Pharmaceuticals website. Joining me on today's call from NRX Pharmaceuticals are Stephen Willard, Chief Executive Officer, and Seth Van Voorhees, Chief Financial Officer and Treasurer of Stephen will provide a summary of the company's progress, Seth will review the company's financial results, and then Stephen will review upcoming milestones before making closing comments. Following their prepared remarks, Stephen and Seth will be joined by Jonathan Javits, the company's chief scientist, and Matthew Duffy, the company's chief business officer, to address your questions. I will now turn the call over to Stephen.

Thank you, Suzanne. Good afternoon, everyone, and thank you for joining us. We scheduled this conference call to coincide with World Bipolar Day. As you know, bipolar depression is a lethal condition that affects 2% of Americans, nearly 7 million people, and a similar percentage of the world's population. With the commitment of our investors, our team, and our researchers, we aim to literally bring hope to the millions of patients with suicidal bipolar depression and PTSD who have been systematically excluded from the trials of previous antidepressants. Today we will discuss full year 2022 results and provide a business update. As you can see from our filing, 2022 was a pivotal year for NRS. When we filed our 2021 earnings, the COVID pandemic was just winding down and we announced our intention to redirect our energy to NRX's core business, the development of lifesaving drugs for lethal central nervous system conditions with an initial focus on suicidal bipolar depression. As we promised investors a year ago, we have now completed manufacture of NRX 101 and aligned with the FDA on a path to commercial stage product. We've reinstituted our clinical trials for NRX 101 for patients with suicidal treatment-resistant bipolar depression We've continued to align with FDA on a path to approve NRX 101, and this week we announced encouraging findings from the first evaluation of unblinded data by our independent data safety and monitoring board. As you know from the online publications we have posted, this DSMB initiative is being led by a highly experienced executive team together with leading psychiatrists from around the world. Today we are delighted to announce the appointment of two world-class psychiatrists to our advisory board. Professor Andrew Nirenberg, a chaired professor of psychiatry at Harvard Medical School, is the director of the Dotton Family Center for Bipolar Research at the Massachusetts General Hospital and one of the world's most published scientists in the area of psychiatric research, particularly as it relates to bipolar disease. We are honored to have him as principal investigator of our ongoing clinical trials. Professor Marion Legoyer is one of France's leading psychiatrists and an extensively published researcher in the field of neuropsychiatry, particularly as it relates to bipolar disease and autism. In addition to her academic achievements, Professor Legoyer chairs the Fondation Fundamentale and has facilitated an important collaboration with French psychiatry researchers that I will describe in a few moments. Please see their biographies on our website. I'll begin by reviewing our lead development program, NRX-101. NRX-101 is a fixed-dose combination of d-cycloserine, an NMDA receptor modulator, and lorazodone, a standard-of-care medicine for treating bipolar depression. We initially introduced NRX-101 as a drug that showed benefit in conjunction with ketamine in acute care patients, and this week announced encouraging findings from our outpatient trial of NRX-101 versus lorazodone that may offer a path to a far broader indication. NRX-101 aims to target a critical area of unmet need among patients with bipolar depression, PTSD. And as you will see in our filings, possibly chronic pain. Multiple investigators around the world have published encouraging findings on the use of d-cyclosterine in these areas. However, the NRX discovery of the unique synergy between NMDA and 5-HT2A targeted drugs, together with the discovery of the critical dosages at which d-cyclosterine may be effective in these conditions, has resulted in a portfolio of 90 patents around the world 48 of which have now been issued, all related to the treatment of bipolar depression, major depressive disorder, PTSD, and other central nervous system conditions. It is well established that patients with bipolar depression are at far greater risk of self-harm than those with major depressive disorder. Tragically, however, patients with suicidal bipolar depression have been excluded from the clinical trials of known antidepressants. To our knowledge, NRX is the first company to attempt to bring a medicine to people whose only FDA-approved treatment alternative is currently electroshock therapy. D-cyclosterine has been shown to reduce suicidal ideation in our stable V trial and similarly been shown to reduce suicidal ideation by independent investigators in a peer-reviewed study reproduced in our 10-K filing. The tragic reality of bipolar depression is that if you know two people with this condition, the odds are that one will attempt suicide. And if you know five people with this condition, the odds are that one will die from suicide. As the first potential oral NMDA antagonist to target bipolar depression with suicidality, NRX 101's proof-of-concept data from the Phase II stable B trial has shown a highly differentiated therapeutic profile compared to the other commercial therapies and investigative drugs under development. Our Phase II data showed a statistically significant reduction in both depression and suicidality compared to standard therapy in patients with bipolar depression who were acutely suicidal and those who were initially stabilized with ketamine. To our knowledge, no oral drug therapy has ever demonstrated a reduction in in both depression and suicidal tendencies in this patient population. This is a potentially life-saving event because antidepressants carry black box warning labels regarding the potential for increased risk of suicide in vulnerable populations. Based on NRX 101's differentiated therapeutic profile, we believe that we have the potential to address this significant unmet need for patients who are currently underserved by available treatment options. Based on our Phase II results, the FDA granted breakthrough therapy designation and a special protocol agreement for NRX101 in bipolar depression with acute suicidality. The breakthrough therapy designation allows for an expedited rolling submission of a new drug application for investigational drugs that have demonstrated substantial improvement over existing approved therapies. and the special protocol agreement allows for a single registrational trial of NRX101 in this indication after stabilization with ketamine, using a protocol similar to the STABLE-B trial with a patient population of fewer than 100. During 2022, we made substantial progress in advancing our development plans for NRX101 for the treatment of bipolar depression with suicidality, as well as a new area, PTSD. As you recall from our initial public filing, our psychiatry drug development program was halted by the closure of psychiatry study sites during the COVID pandemic. This time last year, we advised investors that we were reinitiating our psychiatry program. Our first order of business was to transfer our manufacturing and analytic technology to the United States, and we were fortunate to secure Alchemy, headquartered in North Carolina, as our lead manufacturing partner. Over a period of six months, we transferred our manufacturing and analytic methods to Alchemy. And by September, manufactured our first phase three and potentially commercial scale batch of NRX101. We submitted our manufacturing and stability data to the FDA in October 2022. And in January 2023, we reached alignment with FDA on our proposed manufacturing plan based on a type C meeting to review our chemistry, manufacturing, and controls. As a result, NRX is now positioned to conduct registrational trials of NRX 101 and able to make NRX 101 available through expanded access and right-to-try programs for patients who have exhausted approved treatment options. We're excited about this milestone in particular as we believe that adopting a commercial-ready manufacturing process at this stage of our development can lead to a more seamless NDA submission, review, and approval process under our breakthrough therapy designation without the need for bridging studies. In January 2023, we initiated a Phase III registrational clinical trial of NRX-101 for the treatment of severe bipolar depression with acute suicidal ideation and behavior and contracted the first study set. The study was designed to show that following stabilization in the acute care setting, treatment with NRX-101 is superior to lorazodone in maintaining improvement in symptoms of depression as measured by the Montgomery-Asperg Depression Rating Scale total score. We met with the U.S. FDA earlier this year to discuss the design of this Phase III trial of NRX-101 and in patients with bipolar depression suffering from acute suicidality, and are following FDA's suggestion to pursue the indication of, quote, treatment of recently suicidal patients with bipolar depression. We conducted our initial stable B trial of NRX101 versus lorazodone in acutely suicidal patients following acute stabilization with ketamine. However, both FDA and prospective commercial partners have suggested broadening the indication to test the use of NRX-101 as a means of maintaining remission for acute suicidality in patients stabilized by a variety of standard inpatient approaches in order that our label, should we prove safety and efficacy, not be dependent on prior use of ketamine. Although NRX is not actively researching the use of ketamine, a potent NMDA antagonist We do recognize its role as a potential agent for stabilizing acutely suicidal patients and recognize FDA's desire for more data on its efficacy. Therefore, we have partnered with the leading psychiatrists in France who conducted what we believe to be the most comprehensive study of ketamine for treatment of acute suicidality among hospitalized patients, particularly patients with bipolar depression. Their study, which is summarized in tomorrow's 10-K filings, demonstrates that patients with bipolar depression had a seven-fold greater response to ketamine in reducing suicidality than did those with major depressive disorder. Our colleagues have provided us with a detailed clinical study report that we have now translated into English and are submitting to the FDA. To our knowledge, this is the first multicenter placebo-controlled trial that shows an enhanced benefit of NMDA-targeted drugs in patients with bipolar depression compared to those with major depressive disorder. We look forward to having Professor Leblayet and her colleagues explain the importance of this study in greater detail and accompany us to the FDA to discuss the findings. In the January 2023 Type B meeting with the FDA's Psychiatry Division to align on the registration strategy for NRX101, FDA suggested a potential expanded indication for NRX101 in addition to reaffirming NRX 101's special protocol agreement, which was originally granted in April 2019. The FDA suggested that NRX's clinical development program be enlarged to allow for the chronic treatment of patients with bipolar depression and intermittent suicidality. This update would broaden the addressable population of the indication, under the SPA or otherwise, to patients with chronic intermittent episodes of bipolar depression and would enable the use of NRX 101 on a long-term basis by a broader segment of the approximately 7 million individuals in the United States with bipolar disorder. Prior to pursuing this extremely broad indication, we have focused our outpatient clinical trial first on those of greatest unmet medical need, specifically those with suicidal treatment-resistant bipolar depression. In other words, we are enrolling patients who are under the care of a physician for bipolar depression and have ongoing depressive symptoms and active thoughts of self-harm despite treatment with available medicine. The object of the double bond study is to demonstrate NRX 101's ability to significantly improve symptoms of depression and suicidality over six weeks when taken twice daily on a home use basis. The population is significantly larger than the severe and bipolar depression population with acute suicidal ideation and behavior seen in the hospital emergency setting and does not require initial stabilization with ketamine or other treatment. This study has the potential to expand the use of our medicine to nearly one million people who currently suffer from severe depression and suicidal ideation despite expert medical care with currently available medicine. These are the patients who are targeted by the recently funded $50 million Patient-Centered Outcomes Research Initiative, which documents the extraordinary unmet medical needs in this area. We announced the initiation of this clinical trial when we met with you a year ago, and this week announced guidance to continue enrolling patients by our independent Data Safety Monitoring Board, what I call a DSMB. who examined unblinded data from the first 50 patients. The DSMB found no futility signal at this stage of the trial. Similarly, no safety signals were identified in association with NRX 101, and the DSMB recommended that the enrollment of the trial continue as planned. According to the study's statistical analysis plan, the failure to identify futility requires that an advantage though not yet a statistically significant advantage, of the investigational drug relative to the comparator treatment must be observed by the DSMB. The DSMB will continue to monitor safety and efficacy in the trial. Based on the DSMB's findings, together with the recent completion of Phase III Anticipated Commercial Stage Manufacture of NRX-101, the company has upgraded the ongoing trials with Phase II B-3 trial whose results may be used in a future registrational filing should the primary endpoint commit. With the guidance to the DSMB at hand, the company has now requested a comprehensive breakthrough therapy planning meeting for NRX 101 as was suggested by FDA in their recent correspondence. Based on the comments and guidance from the FDA in its recent Type B meeting, regarding the registrational acute suicidality trial and a potentially broader indication, as well as the guidance we received from the DSMB regarding our currently enrolling Phase 2B-C, sorry, 2B-C3 clinical study of NRX-101. The company is evaluating changes to its registrational program for NRX-101 and will seek to consolidate the current clinical trial. This broader indication may also offer significant advantages in commercialization. Data is expected by the end of this year. We are evaluating the potential of NRX 101 in post-traumatic stress disorder, or PTSD, another area of high unmet need, which is also associated with suicidality. Approximately 9 million individuals in our country experience PTSD. and one-third have severe PTSD with 10% experiencing suicidality. Between 17 and 22 members of our armed forces of veterans are lost every day to suicide. Depression and PTSD may be driven by pathways that are similar to those that drive depression and other conditions. However, NMDA antagonists are the class, and d-cycloserine in particular may have a more specific effect in the treatment of PTSD. In a preclinical PTSD study described in today's filing, tomorrow's filing, B-cycloserine demonstrated the ability to extinguish recurring images of traumatic events, also known as fear memory, in a validated WKY model of PTSD. This model has similarly been used by others to document a PTSD-specific effect of ketamine, Repeated IV ketamine has also been demonstrated to improve PTSD scores in a randomized controlled trial. Unlike ketamine, however, NRX-101 is not neurotoxic, is not addictive, and has not caused psychedelic side effects in clinical trials. We anticipate that our investigational drug will show antidepressant effects in PTSD compared to placebos. And we hope that it will demonstrate specific effects of fear memory component of PTSD and directly reduce symptoms of PTSD itself. Today, there is no approved medicine for these specific PTSD symptoms. We are on track to initiate a phase two study of NRX 101 and PTSD in the second quarter of 2023. We are incredibly excited about the potential life-saving effects of NRX 101. And in order to continue to support the clinical development of these programs, we announced the close of a $2.9 million registered direct offering to support our pipeline efforts, and more specifically, the initiation of an expanded access protocol and safety database for NRX 101, studying treatment-resistant bipolar depression with risk of self-harm. This database allows us to investigate the expanded indication put forth by the FDA's Psychiatric Division in our Type B meeting for our registrational trials, and we look forward to providing you all with an update of our clinical activity in the months to come. The continued financial support from our existing shareholders based on our existing data and ongoing clinical trials demonstrates their commitment to people living with serious CNS disorders and the potential of NRX-101 to become commercially successful. Finally, we achieved a number of significant corporate milestones in recent months. In February, we received notice of the issuance of a U.S. patent for NRX 101, which covers the use of NRX 101 to treat patients suffering from depression, including bipolar depression or major depression, with or without suicidality. This patent strengthens the company's intellectual property position until at least 2033. We are pleased to announce that Matthew Duffy has joined us as Chief Business Officer of the company. Many of you may know him from his time at leading pharmaceutical and biotechnology companies, including Pfizer and Medimine, and his efforts in investor relations and investment banking. Matt will be responsible for a range of duties, including investor relations. Similarly, Dr. Martin Brescher, a distinguished psychiatrist who has held leadership positions at the FDA, AstraZeneca, Johnson & Johnson, and other leading corporations, and serving as medical director for our clinical trials. These milestones achieved in the years since we reentered psychiatric drug development establish a strong foundation for NRX that enables us to efficiently advance our clinical trials and make a difference in the lives of patients with life-threatening psychiatric diseases. I would like to express my gratitude to the patients, the NRF team, clinical trial investigators, and shareholders for their continued support. With that, I will turn it over to Seth for a review of our financial results. Seth?