NRX Pharmaceuticals, Inc. Q1 FY2022 Earnings Call

Greetings and welcome to NRX Pharmaceuticals First Quarter 2022 Earnings Conference Call. At this time, all participants are in listen-only mode. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Tom Johnson from Investor Relations. Sir, please go ahead.

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 Law. 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. 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-Q that we're filing today, which will be accessed from the investor's page of the NRX Pharmaceuticals website. Joining me on today's call from NRX Pharmaceuticals are Robert Besthof, Interim Chief Executive Officer, and Ira Strassberg, Chief Financial Officer and Treasurer. Robert will provide a summary of the company's progress before turning it over to Ira for review of the company's financial results. Following their prepared remarks, the management team will address investor questions. I'll now turn the call over to Robert.

Thank you, Tom. Good morning, everyone, and thank you for joining us today. We appreciate your attendance and look forward to summarizing our progress on our strategic priorities that are guiding our work in 2022. So let's begin. On our previous Year-End Earnings Call, we announced our new strategic focus for 2022, concentrating on our two late-stage drug candidates: NRX-101 for the treatment of severe bipolar depression with acute and sub-acute suicidality, and ZYESAMI in its intravenous formulation for the treatment of critical COVID-19 and potentially other respiratory diseases. We believe these two drug candidates have shown solid scientific evidence to potentially help patients in these areas of very high unmet needs and serve as a platform for numerous indications in other respiratory and psychiatric conditions. Congruent with our strategy to shift treatment paradigms, both drugs could fill significant therapeutic gaps. NRX-101 could become the first oral drug for bipolar depression in patients with acute and sub-acute suicidality. As you know, recent events have had a significant adverse impact on the mental health and well-being of our nation. We've all heard about the recent loss of lives due to suicide of well-known individuals and those only known to a few. The infections have decreased, but COVID is still with us, and in our opinion, it will remain a global health threat. Despite promising data from emerging oral medications for patients at earlier stages of the disease, for patients with critical COVID-19 who are on high nasal flow or on respirators, there's still a large therapeutic gap. We're still losing nearly 300 patients daily to COVID. So let's talk about our psychiatry franchise in NRX-101. As we previously announced, we've reinitiated development of NRX-101 within our psychiatry franchise. NRX-101 is a patented oral medicine that could enable patients with bipolar depression and acute and sub-acute suicidality to be treated on an outpatient basis. Both components in NRX-101 are not scheduled substances and have not shown abuse potential, which could be a very important differentiator, as NMDA antagonists such as ketamine can be highly addictive. The treatment options for such patients are very limited, as antidepressants carry a warning about the potential for increased risk of suicidal thoughts and behaviors. Unfortunately, patients with a risk of suicide have been excluded from the majority of clinical studies for depression. Last week, we announced that enrollment began in our Phase 2 trial for patients with bipolar depression, with sub-acute suicidal ideation behavior or SSIB. In this study, patients are being treated only on an outpatient basis because this group does not require hospitalization. Additional sites are being activated for the 70-patient study, and we're targeting data by the end of the year. It is important to note that every year, we lose nearly 50,000 people in the U.S. to suicide, a figure that does not include lethal drug overdoses in this population, likely understating the actual number. In the U.S., we estimate that about 150,000 to 180,000 individuals with bipolar depression and acute suicidal ideation behavior or ASIB are hospitalized, and about two to three times as many have bipolar depression and thoughts of suicide but do not require hospitalization yet. Overall, this represents a very high unmet medical need. It is estimated that around 50% of individuals with bipolar disorder attempt suicide in their lifetime, and between 11% to 20% unfortunately die by suicide. Given this very high unmet need, these are the individuals that we aim to help with NRX-101. Strategically, this positions NRX in a different segment than others working in the NMDA field, as others have focused on the traditional depression and treatment-resistant depression market, which is a much more crowded space. Recall that antidepressants, including those recently approved for bipolar depression, carry a warning for the increased risk of suicide. We believe NRX Pharmaceuticals can offer patients a highly differentiated treatment option. To the best of our knowledge, NRX-101 is the only oral drug in advanced clinical trials designed to address bipolar depression with suicidality. We were awarded breakthrough therapy designation by the FDA for NRX-101 for severe bipolar depression in patients with ASIB after initial stabilization with an effective therapy. We plan to start a new NRX-100 special protocol agreement study and NRX-101 for patients with ASIB in the second half of 2022. Recall that the FDA provided guidance that initial stabilization should be done in a separate one to three-day study. Those that stabilize can enroll in our NRX-101 versus control study in which the primary endpoint is depression. This study will be conducted with commercial level material and if successful, could lead to our new drug application with the FDA for NRX-101. It's important to note that we're starting this study with commercial level material, which positions NRX Pharmaceuticals well for potential NDA and commercial efforts. This psychiatry franchise is the foundation of our company, and we see the potential for a highly differentiated product in a broad therapeutic landscape. We're also considering exploring other high unmet need indications, such as PTSD with suicidality. Our intellectual property estate offers a range of options to combine other molecules and NMDA receptor antagonists, including with D-cycloserine, which is a component in NRX-101. Turning now to ZYESAMI, which is our proprietary formulation of aviptadil for the treatment of patients with acute respiratory failure in critical COVID-19 and potentially other respiratory diseases. ZYESAMI is currently being evaluated in an intravenous form in a second Phase III study of patients with critical COVID-19 who are experiencing respiratory failure. This is the ACTIV-3B study, which is sponsored and managed by the U.S. National Institutes of Health or NIH. ZYESAMI was selected from a large number of other agents based on promising signs and data from our own studies. We believe ACTIV-3B is a vital study for our country in the fight against critical COVID-19. Following a decline in cases, signals indicate that cases are once again on the rise with the Omicron BA.2 subvariant. According to a May 2022 update from the CDC COVID Data Tracker, we're still losing nearly 300 people in the U.S. daily to COVID-19, and has lost nearly 1 million people total to this virus. According to a recent article, officials expect a spike in cases in the fall. Clinical experts signaled that the BA.2 subvariant of Omicron is highly transmissible. Therefore, we believe there will be continued demand for improved therapies to treat the advanced stages of COVID-19, especially critical COVID-19. Last month, we announced the filing of a new breakthrough therapy designation request with the FDA. This submission includes data from a post hoc analysis of patients who were also treated with Remdesivir and whose respiratory failure due to critical COVID-19 continued to progress. You may recall that our original BTD request was submitted in September last year, which the FDA did not grant. In its response, the FDA requested new clinical evidence comparing the safety and efficacy of ZYESAMI relative to other existing therapies for critical COVID-19, such as Remdesivir. Based on the FDA's input, we performed a post hoc analysis of our completed Phase 2b/3 study focused on the approximately 70% of patients that continue to progress with COVID-19 respiratory failure and also received treatment with Remdesivir. This analysis showed that for these patients who were already treated with Remdesivir and continued to deteriorate, ZYESAMI showed a highly significant four-fold increase in survival odds compared to placebo at 60 days. Safety data is crucial and has been an area of focus of the FDA. This new filing included a recently completed cumulative safety analysis of about 750 patients across all programs treated with intravenous ZYESAMI for critical COVID-19. Our cumulative safety analysis identified no newer adverse drug reactions, indicating an overall safety profile of intravenous ZYESAMI for critical COVID-19 that we believe is congruent with its use in the ICU in a critical care setting. In February, we submitted a new emergency use authorization request, also focused on this narrower patient population. We continue to make progress on the manufacturing of ZYESAMI, recently reaching up to eight months of stability in both the refrigerated and frozen forms. This is important, as we do not know what the future of COVID-19 may hold. The limitations of currently available therapies for COVID-19 were highlighted by the results of the solidarity trial study recently published. In particular, for those in the more advanced age group with critical COVID-19. While promising data for oral compounds has emerged for the treatment of patients with earlier forms of COVID-19, these agents do not work in all patients and may not be suitable for patients on respirators with critical COVID-19. In spite of the advent of Paxlovid, we're still losing nearly 300 people to COVID daily. Our view is that COVID-19 is likely to become endemic and may add 200,000 to 300,000 cases per year. During the first quarter, it was announced that the NIH ACTIV-3B trial has been cleared to complete enrollment. This trial is certainly a key study for NRX, in our view, also for our nation's fight against COVID-19. It is scheduled to enroll 640 patients and enrollment has reached almost 75%. ZYESAMI is the only new investigational treatment drug in this study focused on patients for whom there are few alternative therapies, especially once patients reach respiratory failure due to COVID-19. Recall that patients in this study are tracked for 90 days. The next data safety monitoring board meeting is scheduled for May 25th of this year, instead of an originally planned meeting in April. The NIH ACTIV-3B trial leadership indicated that this new timing would allow the vast majority of patients enrolled today to have reached the end of the observation period for the endpoint at 90 days. We expect data from this trial by the end of the year, notwithstanding periodic DSMB reviews. We continue to believe that ZYESAMI could be a valuable therapeutic for those with COVID-19 respiratory failure who have exhausted all available therapies, especially as they reach the critical COVID-19 stage. To summarize, we see the following potential paths for ZYESAMI in 2022: first, our ongoing EUA application for ZYESAMI with the narrower patient population; and second, the filing of a traditional new drug application with the FDA for ZYESAMI should the NIH ACTIV-3B study data support this. With data expected later this year, under fast-track, we're allowed to initiate submissions of parts of our NDA, which could accelerate the process if the NIH study is successful. We will also explore submission of ZYESAMI under the accelerated approval pathway early in the second half of the year. The FDA instituted the accelerated approval program to allow for early approval of drugs that treat serious conditions and fill an unmet medical need based on existing clinical evidence. As previously disclosed, ZYESAMI showed a series of positive biomarker data that correlated with positive outcomes. As mentioned in prior communications, we have partnerships with Cardinal Health for third-party logistics and distribution services, and with IQVIA for commercial and medical pharmacovigilance support upon potential EUA or NDA approval. With that, I will turn it over to Ira for a brief overview of our financial results.

Thank you, Robert. And good morning, everyone. I would like to start by providing an overview of our financial results for the first quarter of 2022. When comparing to the first quarter of 2021, please note that the company was privately held during the first quarter of 2021. Research and development expenses for the three months ended March 31st, 2022 totaled $5.5 million, compared to $2.9 million for the quarter ended March 31st, 2021. The increase was primarily driven by an increase in clinical trials and development expenses related to ZYESAMI. General and administrative expenses for the three months ended March 31st, 2022 totaled $10.2 million compared to $2.1 million for the three months ended March 31st, 2021. The increase of $8.1 million was primarily related to an increase of $4.4 million in legal, professional, and accounting fees, an increase of $2.2 million in insurance expense, an increase of $0.8 million in stock-based compensation expense, and an increase of $0.7 million in other general administrative expenses. The general and administrative expenses for the three months ended March 31st, 2022 and 2021 included $1.1 million and $0.3 million, respectively, of non-cash stock-based compensation. For the three months ended March 31st, 2022, NRX Pharmaceuticals recorded gains of $2.1 million and $0.2 million for the change in fair value of earn-out cash liability and warrant liability, respectively. NRX Pharmaceuticals recorded no such gains in the first quarter of 2021. For the three months ended March 31st, 2021, NRX Pharmaceuticals recorded reimbursement expenses from Relief Therapeutics of $0.8 million, a $0.1 million gain on extinguishment of debt, and a non-cash settlement expense of $21.4 million related to the gym warrant. NRX Pharmaceuticals recorded no such items in the first quarter of 2022. The net loss for the three months ended March 31, 2022 was $13.4 million or $0.21 per share compared with a net loss of $25.5 million or $0.71 per share for the three months ended March 31, 2021. For the three months ended March 31st, 2022, NRX Pharmaceuticals used $10.4 million of cash in operating activities, compared to $3.0 million during the three months ended March 31st, 2021. As of March 31st, 2022, NRX Pharmaceuticals held cash of $40.2 million compared to $27.6 million as of December 31st, 2021. We believe we have sufficient cash to support operations for at least the next 12 months.

Thank you, Ira. In conclusion, we're executing on our development plans for our two late-stage potentially life-saving drugs: NRX-101 for bipolar depression in patients with acute and sub-acute suicidality, and ZYESAMI delivered intravenously for critical COVID-19 patients. Both drugs, if successful, could significantly change patient care in their respective areas, as they have properties that could make them highly differentiated products. Data is expected for both within the next nine to 18 months. We also see opportunities to leverage both compounds in other populations and disease areas with high unmet needs, which we are also exploring. An area of high unmet need is suicidality. Recall that ZYESAMI has applicability for ARDS that is not related to COVID. A Phase 1 study in sepsis ARDS was actually the basis for us starting our COVID-19 program. And there are other indications as well. We're excited about restarting development work in our psychiatry franchise as the COVID pandemic has, unfortunately, created a mental health strain on our nation. NRX Pharmaceuticals was founded on the commitment to the application of innovative science to known molecules to address very high unmet medical needs. This continues to be our focus, and we remain confident in the opportunities before us. Tom, we're ready to take some questions.

Thank you, Robert. Our first investor question is: what is your view regarding the impact of potential approval of nerve's drug and also Paxlovid being used?

Both medicines are oral options aimed at treating early COVID-19 cases. Paxlovid has been available for a few months, but it doesn't work for everyone and must be taken shortly after symptoms begin. There is another oral medication tested in moderate and severe COVID-19 patients. ZYESAMI is specifically for critical COVID-19 patients, such as those in the ICU or on high-flow nasal support or intubated. It’s important to remember that Paxlovid was part of the ACTIV-3 study but was discontinued for critical COVID-19 due to lack of efficacy. ZYESAMI is currently the only medication still being evaluated in the NIH ACTIV-3 protocol for critical COVID-19. Additionally, the White House has recently predicted new COVID-19 waves this winter. Given this, we recognize a significant ongoing need for treatment options for patients with critical COVID-19.

Okay. Our next question, Robert, how do you see NRX-101 in comparison to its competitors which are in late phase 3?

That's quite an interesting question. Well, first, their programs validate the mechanistic approach of combining an NDA antagonist with a 5-HT2 compound. As I mentioned in my remarks before, we have positioned NRX-101 in the bipolar depression with suicidality space for which the FDA awarded us breakthrough therapy designation. Their programs are focused on major depressive disorder and treatment-resistant depression, adjunctive treatment, etc. We know that up to 50% of individuals with bipolar disorder attempt suicide or experience serious thoughts of suicide over their lifetime, and between 11% and 20% unfortunately succumb to suicide. We also think that it's advantageous that both components of NRX-101 are not scheduled, as abuse potential is of high concern. We also think that studying patients for depression and suicidality is of great importance in the bipolar space, given the warnings about increased risk of suicide carried by current drugs. We also have built a solid intellectual property position for NRX-101, including composition of matter patents.

Okay. That's all the questions we have. Thank you, everyone. This is all the time we have for questions. Thank you all for joining us this morning. This concludes the NRX Pharmaceuticals First Quarter 2022 Results Conference Call. Thank you all for participating.

Thank you very much. Ladies and gentlemen, this concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.