CEO and CEO of NRx Pharmaceuticals. One point I'd like to make before starting is that in addition to Dr. Javitt's many accolades and awards, he was also recently awarded a medal for participation in a Coast Guard search and rescue operation as an aviator. As one who grew up along the Atlantic Coast, I frequently would be going back to shore when the wind and the water got too rough and would see the Coast Guard going out to save people. I can appreciate the dedication and the service and would like to thank Dr. Javitt for that on behalf of everyone in the audience. Dr. Javitt, please go ahead with the presentation. Thank you, Robert. Your comment's touching, but it also relates directly to our topic for this morning because despite the Coast Guard's mission in saving lives, it's publicly known that last year the Coast Guard stood down the entire force for training in stress resilience and suicide prevention because, like any first responder organization, our people have a higher rate of suicide than the rest of the civilian population. This is a problem as we're going to be discussing in active duty, in veterans, in first responders, and at NRx, this is a major part of our focus. Are you seeing my slides? Yes. Thank you. A lot's happened in the last couple of months since our last investor presentation and very much looking forward to sharing it with you. Yeah, we're a micro-cap biotechnology company. We're not really expected to have revenue as these things go, but we intend to buck that trend and actually start showing our investors revenue, perhaps in trickles this year and larger amounts next year and even more the year after. That's based on three lead programs that we've got going on. The first is NRX-100, a drug that many know as intravenous ketamine. You might say, well, it's an old generic drug. How can this be a new drug? In fact, ketamine is labeled only as an anesthetic today. Its use in psychiatry is completely off-label and therefore not reimbursed by insurance. We're in the process of engaging with the FDA on the filing pathway for a new drug application. They granted us a very broad fast-track indication in August for treatment of suicidal ideation and depression, including bipolar depression. We've patented a preservative-free presentation of ketamine. FDA granted us a filing fee waiver for the NDA, and we're applying for a Commissioner's National Priority Voucher, which we'll tell you more about. If that works, that's really an ideal path to drug approval. To do that, we're bringing efficacy data from four well-done clinical trials, but more importantly, real-world data from more than 180,000 people who have been treated with ketamine over the last several years. We believe that should this drug be approved, it's a greater than $2 billion addressable market. As many people know, Johnson & Johnson has an esketamine nasal spray that's approved to treat depression, but specifically says it doesn't lower suicidality. That drug was reported to have sold $1.3 billion last year. The other drug that we're bringing forward is NRX-101, a fixed-dose combination of D-cycloserine and lurasidone. We were granted breakthrough therapy designation for this drug before COVID. We've not yet shown that D-cycloserine plus lurasidone is better at relieving depression than lurasidone alone, although clearly it would be better than placebo. However, we have shown that this is the first drug that's ever reduced suicidality, first oral drug that's ever reduced suicidality in akathisia. Our plan is to submit an application for accelerated approval based on that indication for people who have suicidality and akathisia despite currently available medications while we prove the larger indication of superiority to placebo in reducing depression on the major scale. Finally, we're in the process of assembling a network of HOPE Therapeutics clinics to unite medications with interventions such as transcranial magnetic stimulation and hyperbaric oxygen, all of which are neuroplastic therapies. I'll say a lot more about that in a couple of minutes, targeting depression, PTSD, ultimately, autism, traumatic brain injury, cognitive dysfunction. You've seen announcements from us that we've acquired the first several clinics, and we expect to be acquiring more on a regular basis going forward. We have three new opportunities that we're getting our arms around. Those too can have significant revenue implications. One is the generic form of ketamine. As some of you saw when we put NRX-100 through the FDA back in August, they said, no, you can't file that also for the generic label because the salt concentration is very slightly different. It was 6% different from the generic concentration. FDA said, no, you need to make the salt concentration the same. We did. We're refiled. We're back on file. KETAFREE, which is our preservative-free ketamine for generic use, that is used in anesthesia, pain control, the places where ketamine is currently used, is back on file. We've filed a citizen's petition with the FDA saying, please take the toxic preservatives out of all ketamine because there's absolutely no reason to be giving people intravenous benzethonium chloride every time we give them ketamine. We've brought the manufacturer of this drug back to the United States. It's been offshore for quite some time with innovative diversion-resistant packaging. This is a $750 million current market. That's how much ketamine is being sold for a drug that's in chronic drug shortage. Often, providers have to go to compounding pharmacies because they can't get FDA-regulated, properly manufactured ketamine. We're quite optimistic that we're going to have this on the market in the first half of 2026. The other thing that's happened quite recently that's important to understand is that NRX-100, that is IV ketamine, has just been shown to be a very powerful drug potentially for treatment of PTSD. People always thought it might be good for PTSD. Everybody assumed that it reduces the symptoms of PTSD. Now we know from a trial published just in August in real-world data, intravenous ketamine reduced the PTSD symptoms irrespective of its effect on depression symptoms. There are 12 million Americans who have PTSD with no approved drug. The Secretary of Veterans Affairs has said that his first priority is impacting veteran suicide. There is recent data. It began with an initial clinical trial back in 2022 from British Columbia, but now leading stakeholders in psychiatry are confirming the finding that low-dose D-cycloserine, not the higher dose that we're using as an antidepressant, but low-dose D-cycloserine more than doubles the effect of theta burst transcranial magnetic stimulation. I'll say more about that in a little bit. Basically, D-cycloserine has potent neuroplastic effects, that is, promoting growth of new brain connections that are synergistic with transcranial magnetic stimulation. There is no commercial drug that offers low-dose D-cycloserine. It's being compounded and bought from compounding pharmacies. We've got 10 years of experience with this extraordinarily difficult-to-deal-with drug ingredient. It's difficult to deal with because it's readily hydrolyzable. Actually, manufacturing and keeping it stable is more of a challenge than for most APIs. Because of our work with NRX-101, we know an awful lot about D-cycloserine. You should expect to see us file an IND on this opportunity quite quickly. Why are we doing this? We're doing this because suicide is a national crisis. Suicide kills more than 50,000 Americans every year. An American dies from suicide every 11 minutes. According to the CDC, 13 million Americans seriously thought about ending their lives last year. 3.8 million made an active plan to kill themselves. 1.6 million attempted suicide. There is no drug for this lethal condition that takes the best and the brightest among us. For the first time, we're really starting to understand suicidality, not from a psychologic construct, not from a Freudian concept, but from a neurobiology concept. We're understanding that suicidal depression is really a short circuit in the brain that we can treat. We've identified the receptor in the brain, the NMDA receptor, and recognize that NMDA antagonist drugs create new connections. We call that neuroplasticity. Ketamine and other drugs that target this receptor effectively have been shown to achieve a 50% or better clinical response rate. Now, transcranial magnetic stimulation, an FDA-approved technology where you take the same kind of magnets you find in an MRI, put them outside the head, and treat the brain, has also shown a similar response rate. Our belief is that only by combining these therapies—TMS, neuroplastic drugs, hyperbaric oxygen therapy—can you create a durable and sustainable path to treatment and to recovery. That is why we are building HOPE Therapeutics inside of what would otherwise be a biotechnology company. Just to give you an inkling of how far we have come in understanding suicidality as a brain disease, here is an fMRI of a brain in a patient who has active suicidal ideation. You can see those red spots compared to a normal brain. Obviously, this is just scratching the surface, but a tremendous amount has been done to identify suicidal depression as a brain disease. At the same time, suicidality is the only major cause of death in the U.S. where we have not invented the survival curve. The likelihood that somebody newly diagnosed with breast cancer will die of breast cancer is way smaller than it was 20 years ago. Same for prostate cancer. Same for influenza. Even vehicular fatalities have decreased since we invented seat belts and started putting third brake lights in automobiles. At the same time, we have never really addressed suicide as a CNS disease that causes death. Minimal research funding has been allocated. We have no approved drugs that prevent suicide today. It carries enormous social stigma. It can result in incarceration and voluntary treatment. It is still ultra-frequently treated as a psychological rather than a biological disease. We intend to be part of changing that. There are 125 drugs for depression, and every one of them has a black box warning saying that it may cause suicide because of the effect of serotonin drugs on causing akathisia, which is a side effect closely linked to suicide. There is now overwhelming evidence that NMDA antagonist drugs can rapidly reduce suicidal ideation and that neuroplastic drugs can lead to long-term remission. Here is the black box warning I was talking about. Here's an anecdote from public information about a Chicago lawyer who was given a commonly used antidepressant for depression, where he really didn't have, as far as anybody knows, pre-existing suicidal ideation. Within a day, he was nervous, suffering from akathisia. The next day, he threw himself in front of a train. This is a story that has gone on for years. In our construct, there are really four approaches to treating suicidal depression and PTSD that have to be integrated: neuroplastic drugs, transcranial magnetic stimulation, and other forms of neuromodulation that are coming along and being approved by the FDA, hyperbaric oxygen therapy, and the newest on the horizon is digital therapeutics. The problem we have, as I said, is there's no FDA-approved medication for treating suicidal ideation. The only approved therapy today is electroconvulsive therapy, which does indeed reduce suicidal ideation and depression, but at the expense of very significant short-term memory loss. There's an approved form of ketamine, a nasal spray that is esketamine, and the label says it does not reduce suicidal ideation, which is why doctors continue to use IV ketamine off-label. Yes, ketamine has shown empirical evidence. It's shown clinical trials evidence. It's really worth looking at the basic science. This is really a breakthrough study published by Conor Liston at Cornell, showing that if you take mouse brains in a depression model, you'll see that the dendritic spines that enable cells to connect to other cells are atrophied. If you add ketamine to that infusion, within a day, you see sprouting of those dendritic spines and restoration of neuroplasticity. This has been shown in multiple other laboratory experiments. The point is we're treating the biology of suicidal depression. It's that treatment of the biology that's leading to clinical trials results like this, where you can see this is a study of 156 patients in seven French hospitals, a profound effect of ketamine versus placebo in reducing suicidality and depression. A study funded by NIH where ketamine was randomized against midazolam, a profound difference in reduction of suicidality and also depression. When the midazolam patients were re-randomized to ketamine, they showed the same effect in reduction of suicidality as the people who got ketamine in the first place. Then ketamine, an empirical study, was randomized against electroshock. It was non-inferior to electroshock. Statistically, it was superior to electroshock. More importantly, 30% of the electroshock patients had short-term memory loss, which was not seen in the ketamine-treated patients. Now this is coming forward in real-world data. Osmind has shown that when they looked at the medical records of more than 20,000 patients, they confirmed those same clinical trial findings and actually found that intravenous ketamine had a larger effect than esketamine over the short- term in reducing both depression and suicidality. Now there's brand new evidence, and this comes from Osmind, showing that in 8,000 patients with PTSD treated with ketamine, you see profound reduction in the PTSD scores. The PCL-5 scale looks at things that people would ordinarily call flashbacks and other symptoms of PTSD, not just depression. It confirms an earlier 30-person randomized clinical trial where patients were randomized to ketamine versus midazolam and showed that same effect. Neuroplastic drugs are clearly an important part of what we're doing, but so is transcranial magnetic stimulation because the evidence from multiple manufacturers where TMS is being used to treat the brain in patients with PTSD, with depression, with anxiety, with traumatic brain injury is that this technology causes the brain cells to sprout, to form new connections, new synapses. It starts the process of neuroplasticity. The exciting part for us is that when you add a neuroplastic drug to TMS, it's like fertilizing the field before you plant the seed. This initial trial was done in British Columbia, showed a profound difference in the effect of TMS if you treated the patient with a low dose of D-cycloserine versus placebo. That trial has now been confirmed by the Chair of Psychiatry at Harvard McLean, Chair at the University of Toronto, and multiple other sites. That's why we're in the process of putting together an investigational new drug application for a lower dose of cycloserine than we would otherwise have been using in NRX-101 to be used in conjunction with TMS. Not only has cycloserine shown that effect in reducing depression, which is TMS' major target, but you can see in a randomized controlled trial a very significant reduction in suicidality when patients are given TMS using the theta burst stimulation protocol and D-cycloserine compared to TMS with placebo alone. The last technology that we're bringing into HOPE Therapeutics is hyperbaric oxygen therapy. This is a study that was done in Israel with troops suffering from PTSD. Until the ketamine data came out last month from Osmind, nobody had shown a meaningful effect on PTSD with any drug, whereas hyperbaric oxygen showed a very significant effect in reducing the CAPS-5 score compared to treatment with sham. In other words, you put the patient in the same chamber but don't bring them up to two atmospheres of oxygen the way you do with hyperbaric oxygen therapy. Digital therapeutics are in their infancy. You'll hear much more about it. This is an area where I've worked since approximately the year 2000, began in work with the Defense Advanced Research Projects Agency, where video games were used to train initially troops to synchronize breathing and heart rate. It improved combat performance but also reduced combat stress and was then subsequently shown, really in an unexpected finding, to reduce symptoms of depression among first responders. You're going to see this technology advance and become more and more mainstream. That's the reason we're combining these technologies under the clinical umbrella of HOPE Therapeutics because of our belief that there is no one technology that's going to work by itself for treating patients with this very challenging and lethal condition called suicidal depression and PTSD. With recent FDA approvals of rapid TMS protocols where you can do a full TMS treatment in the space of a week, something that used to take 90 days, if you can combine that with neuroplastic drugs, if you can combine that with digital therapeutics, you can start to live up to the promise of give us a week and we'll give you back yourself. You're talking about care that's enormously cost-effective. This is suicidal depression, certainly not the only lethal condition. Generally, a significant cardiac disease intervention, breast cancer intervention, prostate cancer, you're talking about $35,000 for an episode of care. Treating a brain tumor, you're easily talking $150,000. Everything I've talked to you about is a treatment course that can be delivered for less than $10,000. The cost to save a life in this area, aside from the imperative of saving a life, is dramatically less than in other areas of health care. Robert, I'm going to look forward to your questions. Thank you very much, Dr. Javitt. That was a really interesting presentation. It covered a lot of ground. One of the questions early on comes from some of the things you mentioned early in your presentation. The current administration seems to have a different view of mental health and encourages different treatments. What is your view of how they think about suicidality, alternate treatments like psychedelics or ketamine? If you want to understand how much they care about this, take a look at the President's 100-day Cabinet meeting, which he televised, and talked about the priorities of this administration. The first question he asked Secretary Collins, the Secretary of the Veterans Administration, was, what are you doing about veteran suicide? Secretary Collins talked about psychedelic drugs and other things that the VA is working on. Two weeks ago, I gave a presentation at Fort Belvoir, the U.S. Army Museum. I spoke shortly before [Tres Smith], the Senior Advisor to Secretary Collins. Mr. Smith, who's a wounded Marine, said his first day on the job, the Secretary told him, and he said this in public, so I'm happy to repeat it. The Secretary told him that suicide in veterans and reducing suicide in veterans was his number one priority. You've heard the President talk about this. You've heard the Secretary of Health of the VA talk about this. You've heard Secretary Kennedy talk about this. You've heard Commissioner Makary, the FDA Commissioner, say that this is a high priority for the FDA. No prior administration has been focused on suicidal depression and PTSD and reducing this as a cause of death than any administration that's come before. Robert, looks like you're back. Yes. I'm sorry. I got disconnected for some reason. One of the other questions relates to the regulatory timeline for NRX-100. How may the CNPV impact this timeline? If we're granted a CNPV, that would massively accelerate the timeline. If we go through the regular NDA path with our fast-track designation that's been granted, that's probably a six-month to do for timeline.