NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) Q4 2022 Earnings Call Transcript

NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) Q4 2022 Earnings Call Transcript March 30, 2023

Operator: Good afternoon and welcome to the NRx Pharmaceuticals Full Year 2022 Results Conference Call. All participants will be in a listen-only mode. After today’s presentation, there will be an opportunity to ask questions. Please note this event is being recorded. I would now like to turn the conference over to Suzanne Messere, Stern Investor Relations. Please go ahead.

Suzanne Messere: 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 US 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 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 planned to be filed tomorrow, which may be accessed from the Investor Relations sections 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. 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 Javitt, 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.

Stephen Willard: 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 NRx. 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 life saving 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 highly experienced executive team together with leading psychiatrists from around the world. Today, we are delighted to announce the appointment two world-class psychiatrists to our Advisory Board, Professor Andrew Nierenberg, a Chair Professor of Psychiatry at Harvard Medical School is the Director of the Dauten 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 Leboyer, is one of France’s leading psychiatrists and an extensively published researcher in the field of neuropsychiatric, particularly as it relates to bipolar disease and . In addition to our academic achievement, Professor Leboyer, Chairs the Fondation FondaMental and has facilitated an important collaboration with French psychiatry researchers that I will describe in a few moments. Let me 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 lurasidone, 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 lurasidone that may offer a path to a far broader indication. NRX-101 aims to target the critical area of unmet need among patients with bipolar depression, PTSD, and as you will see in our filing, possibly chronic pain. Multiple investigators around the world have published encouraging findings on the use of D-cycloserine in these areas. However, the NRx discovery of the unique synergy between NMDA and 5HT2a targeted drug together with the discovery of the critical dosages at which D-cycloserine 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 to 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-cycloserine has been shown to reduce suicidal ideation in our STABIL-B 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 target bipolar depression with suicidality, NRX-101’s proof-of-concept data from the Phase 2 STABIL-B trial has shown a highly differentiated therapeutic profile compared to the other commercial therapies and investigative drugs under development. Our Phase 2 data shows 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 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 differentiated therapeutic profile, we believe that we have the potential to address a significant unmet need for patients who are currently underserved by available treatment options. Based on our Phase 2 results, the FDA granted Breakthrough Therapy Designation and a Special Protocol Agreement for NRX-101 and bipolar depression with acute suicidality. The Breakthrough Therapy Designation allows for expedited rolling submission of a new drug application for investigational drugs that have demonstrated substantial improvement over existing approved therapy.

And the special protocol agreement allows for a single registrational trial of NRX-101 in this indication after stabilization with ketamine, using a protocol similar to the STABIL-B trial with a patient population of few than 100. During 2022, we made substantial progress in advancing our development plans for NRX-101 for the treatment of bipolar depression with suicidality as well as a new area, PTSD. As you recall from our initial public filings, our psychiatry drug development program was halted by closure of psychiatry study set 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 3 and potentially commercial scale batch of NRX-101. 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 the Type C meeting to review our chemistry, manufacturing, and control. 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 study.

In January 2023, we initiated a Phase 3 registrational clinical trial of NRX-101 for the treatment of severe bipolar depression with acute suicidal ideation and behavior and contracted the first study site. The study was designed to show that following stabilization in the acute care setting, treatment with NRX-101 is superior to lurasidone and maintaining improvement in symptoms of depression as measured by the Montgomery-Ã…sberg Depression Rating Scale total score. We met with the US FDA earlier this year to discuss the design of this Phase 3 trial of NRX-101 in patients with bipolar depression suffering from acute suicidality and are following FDA’s suggestion to pursue the indication of ‘treatment of recently suicidal patients with bipolar depression.’ We conducted our initial STABIL-B trial of NRX-101 versus lurasidone 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 potential agent for stabilizing acutely suicidal patients and recognize FDA’s desire for more data and efficacy. Therefore, we have partnered with the leading psychiatrists and 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 filing, 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 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 Leboyer 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 NRX-101, FDA suggested a potential expanded indication for NRX-101 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 this power 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 care of a physician for bipolar depression and have ongoing depressive symptoms and active thoughts of self-harm, despite treatment with available medicines. The object of the double-blind study is to demonstrate NRX-101’s ability to significantly approve symptoms 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 1 million people who currently suffer from severe depression and suicidal ideation despite expert medical care with currently available medicines. These are the patients who are targeted by the recently fund $50 million Patient-Centered Outcomes Research initiative, which documents the extraordinary unmet medical need in this area. We announced the initiation of this clinical trial when we met with you a year ago and this week, we announced guidance to continue enrolling patients by our independent Data Safety Monitoring Board, what I call it DSMB, who examine 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 Statistical Analysis Plan, the failure to identify futility requires that an advantage though not yet a statistically significant advantage. So, the investigational drug relative to the comparative treatment must be observed by the DSMB. The DSMB will continue to monitor safety and efficacy in the trial. Based on the DSMB’s finding together with the recent completion of Phase 3 anticipated commercial stage manufacture of NRX-101, the company has upgraded the ongoing trial to a Phase 2b/3 trial, whose results may be used in a future registrational filing should the primary endpoint commit. With the guidance for the DSMB at hand, 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 — I’m sorry, 2b/3 clinical study of NRX-101, the company is evaluating changes to its registrational program for NRX-101 and will speak to consolidate the current clinical trials. 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 and 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 experienced 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 of the class and D-cycloserine, in particular, may have a more specific effect in the treatment of PTSD. In our preclinical PTSD study described in today’s filing — tomorrow’s filing, D-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-effect on clinical trial. We anticipate that our investigational drug will show antidepressant effect in PTSD compared to placebo and we hope that it will demonstrate specific effect out 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 2 study of NRX-101 and PTSD in the second quarter of 2023. We are incredibly excited about potential life-saving effect of NRX-101. And in order to continue to support the clinical development of these programs, we announced the close of the $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 trial 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 noticed that the issuance of the US 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 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 MedImmune and his efforts in Investor Relations and Investment Banking. Matt will be responsible for a range of duties, including Investor Relations. Similarly, Dr. Martin Brecher, a distinguished psychiatrist who has held leadership positions at the FDA, AstraZeneca, Johnson & Johnson, and other leading corporation is serving as Medical Director for our clinical trial. These milestones achieved in the year since we reentered psychiatric drug development, establish a strong foundation for NRx that enables us to efficiently advance our clinical trial and make a difference in the lives of patients with life-threatening psychiatric disease.

I would like to express my gratitude to the patient, the NRS 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?

Seth Van Voorhees: Thank you, Stephen and good afternoon everyone. I will now review the highlights of our fiscal year 2022 financial results and our expectations for 2023. For the year ended December 31st, 2022, NRx Pharmaceuticals recorded $17.0 million in R&D expenses compared to $20.3 million for the year earlier. The decrease of $3.2 million is related primarily to the decrease of $2.5 million in clinical trial and development expenses related to our discontinued XIAFAMI clinical work. For the year ended December 31st 2022, we also recorded $27.4 million of general and administrative expenses compared to $74.9 million for the year earlier. The decrease of $47.6 million was primarily related to a decrease of $53.3 million in consulting fees, of which $41 million was related to the fair value of common stock issued.

For the 12-month period ended December 31st, 2022, our resulting net loss was $39.8 million, which is $53.3 million improved compared to the net loss of $93.1 million for the 12 months ended the prior year. In fiscal year 2023, we expect our annual R&D expenses to decrease further from both fiscal year 2021 and 2022 levels as we focus solely on the development of NRX-101. Furthermore, we expect our annual G&A cost will decrease in 2023 due to a number of factors, including reduced legal costs related to the relief therapeutic — therapeutical settlement, which has the potential for a significant royalty payments to us in the future; lower insurance costs, especially related to D&O coverage; and as well as other cost initiatives that we have undertaken.

Now, I’d like to comment on our cash resources. At year end, we had $20.1 million in cash. Our cash resources were enhanced several weeks ago when we entered into a Securities Purchase Agreement with accredited investors who had previously established ownership positions in the company. The transaction involved the sale of approximately 3.9 million shares of the company’s common stock combined with five-year warrants in a registered direct offering priced slightly above market at $0.75 per unit for the securities. The investors agreed not to sell these shares of common stock or exercise these warrants for six months following the issuance of — the issuance date. The aggregate gross proceeds to the company from the offering was approximately $2.9 million.

As of the 10-K filing, we evaluated if there is doubt about our ability to fund our operations for the next 12 months. We have the right to make required payments for our current indebtedness in common stock subject to certain ownership and trading volume limitations. If we are not able to make the required payments for this indebtedness, we will need to raise additional capital to support our currently anticipated operations for the next year to strengthen our balance sheet as was done with the successful offering done several weeks ago. In addition, we may consider additional cost savings initiatives to further extend our cash resources. With that, I will turn it back to Steve for closing remarks. Steve?

Stephen Willard: Thank you, Seth. Over the past year, we have built strong momentum as we advance our NRX-101 program in two indications, while also positioning NRx for future growth with the potential for both the broader bipolar depression population as well as additional indications. Building on that momentum, 2023 promises to be an even more productive year as we continue to execute on multiple regulatory and clinical catalysts. We believe that NRX-101 is a potentially life-saving medicine that could change the treatment paradigm for individuals with bipolar depression who are experiencing suicidality, which is the driving force behind our mission of meeting the needs of underserved patients with serious CNS disorders. We look forward to updating you on our near-term milestones, which are on track for the coming year.

Assuming that efficacy endpoints and safety are met in our Phase 3 trial, we plan to initiate the rolling submission of a new drug application by the end of this year with potential for drug approval by the end of 2024. Operator, Danielle, we are ready to take questions from the audience.

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Q&A Session

Operator: We will now begin the question-and-answer session. The first question comes —

Stephen Willard: Hello?

Operator: The first question comes from Jason Kolbert of Dawson James. Please go ahead.

Jason Kolbert: Hi, guys. Thanks.

Stephen Willard: Hey Jason.

Jason Kolbert: I appreciate — hi, how are you? Thank you for the very comprehensive update. I mean, that is really, really good, very detailed. That’s what we need. Just want to understand a couple of comments you made. The DSMB lack of utility, which implies that the active drug is showing efficacy, equivalent or even better than competitor, although not yet statistically significant. Can you just talk a little bit about that statement and kind of the math behind it, that would be helpful?

Stephen Willard: Sure, Jonathan.

Jonathan Javitt: Sure. Jason, as you know, it’s critical that we keep the blinding for the trial in place the protocol for the trial and statistical analysis plan are up on clinicaltrials.gov. And all we’ve been authorized to say by the DSMB is that no futility signal was identified. And their leading methodologist Dr. Levine said that we could offer the additional comment that in this trial, the way this is set up, for that conclusion to be reached a numerical superiority, though not a statistically significant superiority would have to be identified. There are some trial designs where as long as you’re not worse than the placebo, you’re still not futile, we put in place a stricter futility rule than that. But that’s really all we’re at liberty to say.

Jason Kolbert: Right. But actually that’s very critical, that last sentence when you talked about — because that’s what I was familiar with. But in most clinical trial are designed that if you’re equivalent to the comparator or non-inferior to the comparator, that’s how they’re mostly designed. And what I didn’t understand until this moment was that if your trial design is a little bit different, and in fact, you’re not futile because of the powering — and I’m assuming because of the powering differences and the assumptions around the effect between active and comparator that in fact, if no futility is shown, it suggests that there is a superiority because otherwise — because the numbers are stacked against you because of the tough trial design. Is that kind of Layman’s interpretation about right?

Jonathan Javitt: Well, I don’t think I want to wax overly optimistic. I think we’re delighted that we didn’t hit a futility signal given that we had a fairly strict rule in place. I don’t think it would be necessarily care for us to talk about most trial designs, but we did get permission from our methodologies.

Jason Kolbert: Let me ask the second half of the — sure. I understand. So, I don’t want to beat up this point because you’re limited by what you can say. But I was also very interested from a clinical perspective when you talked about potential modifications of the Phase 3 trial and the combination of the two trials together. Can you talk a little bit about what that might mean? And particularly I was — yes, particularly the timeline–

Jonathan Javitt: Let’s talk about how we got to where we are.

Jason Kolbert: Thank you.