NRX Pharmaceuticals, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Welcome, Jonathan. Thank you, Imogen.

Well, I think it is important to start out with the context. Just as we are observing the 25th anniversary of 9/11, in my case, this is the anniversary of the moment where my closest friend came to me actually in synagogue during Yom Kippur, told me he was having an episode of depression.

That he was going to be seeing one of the top psychiatrists in the country that week, and just wanted me to be involved. Called me up a few days later, told me, "Guy's brilliant. Really understands me. Started me on ZOLOFT, told me I'm going to be fine." I kind of put that in the category of, okay, he's going to be fine. Well, later that week, he went up to Harvard, was invited to give the endowed lecture everybody dreams of giving. Came back to Pittsburgh, kind of crashed from that high. Went to see the brilliant psychiatrist who was off giving his own named lecture. He saw the junior guy, and junior guy said, "You know, this ZOLOFT isn't working well enough. Let's triple the dose and see what happens." What happened was he went home and hanged himself.

That's probably one of the two most shocking things I've seen in my life as a physician.

The only other time I was that shocked and surprised by a medical outcome was somebody I was involved in treating as a medical student who came in with acute myeloblastic leukemia. We gave him chemotherapy, and three weeks later, he was dead from sepsis. At the same time as this happened, my brother Dan was just starting a clinical trial based on work he'd started in the 1980s on the NMDA receptor in the brain. In that clinical trial, they discovered the role of D-cycloserine in mediating the NMDA receptor, decreasing depression and suicidality. I assumed that invention would be snapped up by Big Pharma and would turn into a drug right away, and instead, Big Pharma basically ran away from psychiatry and is only now coming back. So in 2015, we started NRx Pharmaceuticals really around those patents, around D-cycloserine and its effect on suicidal depression.

That's the genesis of our drug, NRX-101. Well, I had no idea where this adventure would lead in that process. One thing it did was led us into a COVID pandemic that put our whole psychiatry program on ice for the better part of three years. But ultimately, as we emerged from that, we already knew that NRX-101 works better after a dose of ketamine.

We had an agreement with the FDA saying that they would allow us to give it after a dose of ketamine. We went back to the FDA and met with them after COVID, and they said, "Well, you know what? We think that if you are going to do that, you have got to change the label on ketamine so that ketamine can be used in this application." You cannot actually change the label on somebody else's drug. Ketamine was owned by Par Pharmaceutical. We had to start our own ketamine. We actually had to become a drug manufacturer and make ketamine, which we have done.

That has led us to KETAFREE.

It led us to realize that there was a toxic preservative in everybody else's ketamine, and we ought to fix that along the way. It also led us to realize that drugs alone are not going to solve this problem. Yes, it is great to modulate the NMDA receptor, which is what all the drugs we are working on do. It is great to modulate the 5-HT2A receptor, and that is CAPLYTA and that whole family of drugs. But it has become very obvious that it is not sufficient, that you really have to add other modalities, and probably the next modality that is becoming mainstream is transcranial magnetic stimulation.

Although NRx has remained at its core a pharmaceutical development company, we started this adventure called HOPE Therapeutics, where we own clinics, we are involved in developing technologies, and you just saw a press release this morning showing that our team, together with the people at Zeta Robotics, Zeta Surgical, are demonstrating the first robotic-enabled neuro navigated TMS. People may say that is science fiction. The nice thing about science fiction is DARPA, the Defense Advanced Research Projects Agency, is in the business of funding science fiction. They funded this crazy thing that turned into the internet. They funded other crazy stuff that turned into the first simulation. In fact, the DARPA program officer who funded that back when he was a Navy lieutenant commander ultimately left as a three-star and is our president of NRx Defense Systems.

That press release that you saw this morning talking about NRx and robotic TMS is all in preparation for a program that we are kicking off with the military. It is going to be 240 patients treated in civilian settings, between 140 and 160 patients treated in military treatment facilities. You may say, "Well, why does the military suddenly care about depression?" The military has to care about depression. People exposed to combat are four times more likely to have depression and PTSD than civilians. It used to be, well, okay, you have depression, you have PTSD, you are suicidal, you are going to be out of the military in two weeks. That just does not work anymore. It does not work for people, and it does not work for the mission. Because a unit that is down 10% in strength is not combat deployable.

If you have a special forces operator who has got depression, you cannot just send him to the VA and go get yourself another one. You are talking about somebody who takes five years to train. Aside from not being kind to people, it is just not consistent with what we need to achieve. All of a sudden, the possibility of a one-day treatment with robotic neuro navigated TMS and our drug D-cycloserine lurasidone, NRX-101, becomes mission critical for one of the largest organizations in the U.S., namely the U.S. military. That is really what the preliminary data show. The preliminary data suggest, and these have been unrandomized trials, unblinded trials, that if you treat with a full day of transcranial magnetic stimulation, sort of 20 sessions in a day, combined with NRX-101, or they actually use generic D-cycloserine, you can find perhaps a 50% reduction in depression that lasts.