Okay, we are ready to get started. So good afternoon, everyone, and thank you for joining us for another Virtual Investor Lunch Break. Today we are featuring CNS Pharmaceuticals. My name is Jenene Thomas. I am CEO of JTC IR, and I will be the moderator for this event. I am very pleased to be joined by John Climaco. He is Chief Executive Officer of CNS Pharma. Welcome, John.
Thanks, Jenene. Nice to be here.
Well, so glad to have you back. We are excited to showcase the CNS Pharma story today on our platform and share this with our audience. So for today's event, we will start with a corporate overview from John, followed by questions from myself, and then we will turn it over to a live Q&A with the audience. Before I get started, I just want to remind our audience that CNS Pharma is publicly listed on NASDAQ and trades under the ticker CNSP. And during today's discussion, the company will be making forward-looking statements, and I encourage everyone to view the company's latest SEC filings on their website at CNSPharma.com for the latest information. So, John, I hope everyone has their lunch. I know it's a great story. I'm going to turn it over to you for an overview of CNS Pharma.
CNS Pharmaceuticals, I'm John Climaco. I'm the Chief Executive Officer. Been with the company pretty much since the founding. And I love this company, and I love this drug, and hopefully you will, by the end of this presentation. So we are a drug development company, and we are specializing in glioblastoma, one of the two worst, deadliest cancers out there. I'll talk a little bit about that in a moment. Our lead program was developed at the largest cancer research institute in the world. That's the MD Anderson Cancer Center in Houston, Texas. Our lead drug is called Berubicin. And what's so special about this? Why do I love it so much? Well, Berubicin is an anthracycline. It's a member of the most commonly used class of chemotherapy drugs in the world.
It's got a couple of really unique features that make it stand out. Number one, it's the only anthracycline to cross the blood-brain barrier. And that means it can. Number two, we have learned so far in our potentially pivotal study, which is going on now, it's fully enrolled with over 250 patients here and in Europe, that this drug does not appear to be cardiotoxic, and that alone would make it stand out among anthracyclines. So as a little preview of what I'm going to conclude with at the end, we think we have a potential game changer here, a drug that can change the standard of care for glioblastoma patients that has been static for the last 30 years, and a drug because of these unique features that has legs and applications far beyond that in other diseases which are much, much more prevalent.
This is a very exciting molecule. It's a very exciting development for cytotoxic chemotherapy, which remains the cornerstone of oncology around the world. We had a very successful interim analysis. I'm going to talk a lot about why we're so confident, but one of the reasons is that our Independent Data Safety Monitoring Board, that's the DSMB, gave us the green light in January to proceed with this study. Study we should continue. They wouldn't have said that. They couldn't have said that by their charter if they didn't see both efficacy and a positive safety signal. So what we're seeing here is continuing buildup of evidence that this drug may be the one to finally crack this very difficult nut. So, sorry. There we go. So glioblastoma for a moment. I'm sure some of you are familiar with this.
I hope not too personally because it is an absolutely awful disease. At diagnosis, your life expectancy is 12-18 months. But in second-line patients, that's patients that have failed the standard of care, which is surgery followed by radiation and treatment with a drug called temozolomide. Those patients, and that's almost everyone, this disease is uniformly fatal, so almost everyone who is diagnosed ultimately will fail standard of care. Those patients, the ones that we are studying, have a life expectancy of 4-6 months. It presents almost half of all primary malignancies in the brain. And there is no approved treatment anywhere in the world for second-line glioblastoma. So again, let me say that one more time. I want to underpin just how awful this situation is for these patients and the magnitude of the clinical need.
No approved treatment for second-line therapy anywhere in the world for glioblastoma. It is, from a regulatory perspective, a completely greenfield opportunity. So why is that, and why is this disease so difficult to treat? It's primarily, in our estimation, not a function of the tumors themselves. They are aggressive. They are very bad. They are the nastiest-looking spider tumor tissue growing among that, you know, beautiful, healthy gray matter that you could ever imagine. They're very difficult to treat. They're almost impossible to completely surgically resect. They're almost impossible to completely treat with radiation. And the only drug that's approved really for first-line therapy, that's temozolomide, diagnosed with this disease, are going to have no effective chemotherapy whatsoever. It's a disaster. We believe that the reason for that is the blood-brain barrier. Now, why is that?
Well, the blood-brain barrier is this very specialized network of cells that surrounds our brain, and the idea is that it protects your brain. It becomes the most privileged sanctuary in your body. Obviously, the brain is required for everything that we do as a human being, and so we were designed to make sure that the brain has the most absolutely bulletproof defense mechanism around it. This network of cells does two things. First, it acts as a tightly woven physical barricade, like a fortress wall around the brain. But more importantly, from the perspective of treating diseases that are growing in the brain, it has an active function as well. That's something called the ATP-binding cassette transporter proteins and the MDR, multi-drug resistance proteins. These two, they are so strong they can push harmful substances away from the brain faster than your heart can pump them in.
Now, unfortunately, for folks that have a brain tumor, that means almost all chemotherapy drugs. And so all these wonderful drugs that we have today for chemotherapy that are effective in lots of different places in the body, they can't get into the brain because they can't bypass the blood-brain barrier. And so what was the innovation that our founder developed that was the beginning of this company? Well, it was an idea at first. And the idea was this: we can treat GBM's tissue and tumors. We can destroy them in the test tube at the bench all day long. You introduce all sorts of chemotherapy agents, all sorts of cytotoxic agents to these cells, and you will destroy them in the test tube. You will destroy them in the lab. However, you will not have the same effect with human beings. The reason is the blood-brain barrier.
So what attracted me initially to the company? Because his idea was perhaps the problem with drug development for GBM is not, in fact, coming up with a novel mechanism of action specific to these tumors. Perhaps the problem is simply the blood-brain barrier. Because what if we could introduce a molecule that we knew was effective, that came from a class of drugs like anthracyclines, that are effective against a couple dozen different tumors around the body, that we know can destroy GBM cells in the test tube? What if we could transport that molecule across the blood-brain barrier? Would it not then have the same effect on those cells that it would in the laboratory? And that was the idea, but a very, very difficult idea to bring to fruition because anthracyclines as a class do not cross the blood-brain barrier.
Now, that is a huge limitation to their use. These drugs treat all sorts of cancer all over the body. Most importantly, from an adoption perspective, these drugs have been in use for almost 75 years. They have been studied extensively. Regulators in every country in the world understand these drugs very, very well. I often say there isn't an oncologist in the world that wasn't trained in medical school on how to use anthracyclines. However, they don't use them for brain cancer simply because they don't cross the blood-brain barrier. There is one exception to that rule, and that is Berubicin. It was specifically designed to cross the blood-brain barrier. Once it gets into the brain, this is its second feature that I really love, and that is it acts just like another anthracycline. So what does that mean?
That means that its design makes it something called a topoisomerase II inhibitor. Topoisomerase II is an enzyme that's critical for cell division. You can't have topoisomerase II being overexpressed. So what does that mean in our brain? Well, hopefully everyone on this call has a nice, healthy brain. And if you do, as an adult, you don't have a lot of rapidly dividing cells. We could all use some more brain cells, but we're not making any more as adults. That's just not how it works. But if you have a tumor growing in your brain, that tumor is in the business of rapidly dividing. That's what tumors do. And in order to do that, they've got to overexpress this enzyme, topoisomerase II. Now, imagine that you're an anthracycline molecule and you're inside the blood-brain barrier.
The only place that you're going to find the very enzyme that you are designed to act against is in tumor tissue, not in healthy brain tissue. So once this molecule crosses the blood-brain barrier, it is going essentially to seek out the tumor tissue because those are the only cells that are overexpressing this critical enzyme. The anthracycline, Berubicin in this case, that was the theory, and it's a very elegant theory. I love it because, most simply put, imagine anthracyclines are the hammer in the oncologist's toolbox. This is really the thing that all it's the first thing that oncologists reach for when they're treating a couple of dozen different cancers. But they don't reach for it for brain cancer because the nail is inside the blood-brain barrier. But Berubicin is the one hammer that can go to the nail and strike.
We know what happens when a hammer hits a nail. That's how this molecule was designed. That was the theory. That was the hypothesis. How did it play out? You can see here just before we get to that, this is really a schematic of what this molecule does. Again, it's an analog of another anthracycline. It was designed specifically to retain that functionality, that cytotoxic functionality, but allow it to cross the blood-brain barrier. How does it cross the blood-brain barrier? It's highly lipophilic. That means it has a very strong affinity to fat, and our brain is the most fat-rich environment in our body. So this molecule passes, unlike all other anthracyclines, into the brain, and then it does, as I indicated, what all anthracyclines do. It seeks out topoisomerase II, and it inhibits that function of that enzyme. So again, this was the theory.
This was how it was designed. How did it play out? It was studied in a phase 1 study, 35 patients, and it was subject to a very rigid and standardized dosing regimen, lots of different measurements on this thing. But what, when the rubber meets the road, of course, we're talking about GBM patients. We want to see what's happening. Are we going to stabilize this disease? And the reason that that's so important, excuse me, is because this is not a disease that spontaneously resolves. This is not a disease that spontaneously stabilizes. These months life expectancy, 4-6 months. This is a disease that is progressing extremely rapidly. It doesn't discriminate. You can be John McCain. You can be Ted Kennedy. You can be Joe Biden. You can be the president of MD Anderson Cancer Center.
If you get this disease, you're going to die from it. And so anytime we see this disease stabilizing, we know that that's because of some intervention. So in this study, Berubicin was introduced to some very, very sick patients. These were patients that had had many rounds of chemotherapy, very close to death. We don't expect to see a lot from them. Really, in fact, the purpose of this study was simply to determine the maximum tolerated dose. But instead, what they found was remarkable because 44% of patients demonstrated stable disease or better. Now, in a disease that does not spontaneously resolve essentially ever or even spontaneously stabilize, this is incredible result. This is an incredible result. We also had two partial tumor shrinkages with up to 80% shrinkage. One patient, a durable complete response, still alive 17 years later.
You can see this gentleman's scans on the right, obvious tumor inclusion there on the left and on the right six months after treatment. He looks the same today, tumor-free and living his life. We don't see this in this disease. We don't see this with anthracyclines because anthracyclines don't cross the blood-brain barrier. So, really quite remarkable results and actually the foundation of what we have been doing as a company ever since. So the idea behind CNS and its focus on Berubicin was in some ways quite simple because we knew in this disease, if we could replicate or actually improve upon the results of the phase 1 study in this disease where there's nothing approved anywhere in the world for these patients, we had a drug that was headed for registration.
But that's easier said than done because the only way to convince FDA that you had a drug that was trial with only one possible endpoint, and that was overall survival. What that means is kind of what it sounds like. That is, who is living longer? The patients taking Berubicin or in this case, the patients taking a comparator drug, lomustine, which is an off-label drug. That is, it's not approved for second-line treatment of GBM, but it is the only thing that is used anywhere in the world really for these patients. And so again, evidence of just how bleak the situation is for these patients. FDA blessed a study with a comparator arm that is an unapproved off-label drug. The only way really to get effective data on overall survival is to have a very large study.
200+ patients were going to be needed, actually more than 250. A lot of folks said it was going to take us 5 years to enroll these patients. We did it in 2.5 years. I think that speaks to the study design, which I'll talk about in a moment. But it also speaks to the strength of the drug and the data behind it. So we had 47 of the leading neuro-oncology centers. Point was overall survival. And that, we arrived at after extensive discussions with the FDA because this drug is both a fast-track drug and an orphan drug. FDA is very highly incentivized to see a drug approved here. They haven't been able to move the needle here for several decades. So, this is a big problem for them.
They really would like to see something happen here, but they've got to show improvement of overall survival. We're collecting a whole bunch of secondary endpoints as well. The mandate essentially being leave nothing on the cutting room floor, anything that could possibly be correlated with improvement for these patients. We want to know about, most importantly for investors, top-line data. That is the completion of this study, will be in the first half of next year, so approximately a year from today. And as I'm sure you know, in the world of drug development, that's a very near-term opportunity. So let me stress, quickly where we are with this. Number one, we are fully enrolled. That means we don't need any more patients. The patient enrollment risk is over, set to go from that perspective. We also have all the drug supply that we need.
We've already manufactured it. It's sitting in our depot. There is no risk on CMC or drug supply. We have everything we need to complete this study and then some. We have all the investigators that we need. We're not seeking out any more stuff, any more investigative sites anywhere in the world. We have them all. The only thing that we are doing right now is monitoring these patients from today until our last outpatient on overall survival. And sadly, that means when those patients expire. So, our objective as a company from the beginning in studying this drug was to wring out all of the risk other than the chemistry and biology. That is, when Berubicin, the molecule, meets the GBM tumor itself, how does it behave?
And I can tell you that within approximately a year, perhaps less, we will have a conclusive answer, a registrable answer from this study, whether that is the case. And I've told you some of the reasons why we believe very strongly that it will. Optimistic about this is that in January, our Independent Data Safety Monitoring Board, our DSMB, recommended that the study of Berubicin that we are conducting continue without modification. Now, that may not sound much, and in fact, the market didn't react particularly well to our announcement of this, but it is big news. And the reason that it's big news is because the only way that they could arrive at that statement was by analyzing both safety and efficacy data. So if the drug did not appear to be safe, they would have recommended that we discontinue this trial and stop it.
Importantly, if they did not see the beginnings of efficacy signal, they would have also had to recommend that we stop the study. But clearly, they must have seen both because they recommended that we continue without modification, which was about the best result that we could have possibly hoped for. Now, one of the things that we learned in efficacy data, DSMB was not, of course, we are. It's the only way to conduct this study because one of our drugs is an infusion, Berubicin. The other is a pill. And so, there's really no way to blind investigators or patients to those outcomes. So, we are blinded. They were not. But we do see the safety data. And in looking at all of this safety data, one of the things that immediately jumped out was incredibly important and unique.
And that was Berubicin does not appear to be cardiotoxic at all. Now, that sounds like a nice-to-have or something that you would want in any drug, but unfortunately, all other anthracyclines are cardiotoxic. That is a serious limitation and Achilles' heel in the use of these drugs. They're all subject to a lifetime maximum. It's very important that the dosing be kept low because cardiotoxicity obviously is a major problem, particularly if you have a cancer that's treatable like breast cancer. You don't want to have a heart failure. Now, it may be less of an issue when you have brain cancer and it's going to kill you in 4-6 months. However, we still don't want to introduce a cardiotoxin for obvious reasons.
So the fact that Berubicin appears to be non-cardiotoxic and crosses the blood-brain barrier distinguishes it from all other anthracyclines and gives us a little hint of where we might be going with this drug, where we have said we were going to be going with this drug from the beginning. And that is this. Anthracyclines, as I said before, have been in clinical use for almost 75 years. They are the hammer in the oncologist's toolkit, but they are subject to two limitations. One, they don't cross the blood-brain barrier historically. Two, they are all cardiotoxins. We eliminate both of those problems.
You can imagine that if you suddenly introduce a member of the most widely used and trusted class of chemotherapy drugs in the world that eliminates both of the limitations of the entire class, you may suddenly have a drug that has application far beyond treating GBM, but we have known from the beginning that it had potential far, far beyond that. This slide really demonstrates why that's so important. We are focused right now on that top slice, the primary brain tumor market. 15,000 patients in the U.S. alone doesn't sound like much. It's a multi-billion dollar opportunity. Temozolomide, the only drug that's used to treat first-line GBM around the world. It's been off patent for almost a dozen years, and it's a $9 billion a year drug globally. Most of that use is in primary brain tumors.
There are other uses, but temozolomide has got some serious limitations. As I said, it usually is effective in only about 4 out of 10 people. And so, that really limits its use, but it certainly doesn't seem to limit its market potential. But when you look at what Berubicin might be able to do, and you look down this chart, particularly look at that third slice, metastatic breast cancer, 45,000 cases a year. That's metastatic to the brain. When those folks, unfortunately, primary brain cancer patients have, which is they've got a tumor growing inside their blood-brain barrier and they don't have a lot of options to treat it. Berubicin can handle that. Berubicin can handle primary CNS lymphoma. We believe Berubicin can handle primary high-grade gliomas in pediatrics.
We believe all for the same reason that we believe it can handle GBM and has been demonstrated to handle GBM. So, this is really a preview for what we think we can do with this drug beyond this. So maybe one question might be, well, then why did you choose the hardest cancer to treat before you started with these? The answer is simple. It was a regulatory-driven decision. Certainly the drug was designed to do this, but when you're dealing with a situation where there are no other approved therapies anywhere in the world, it is as open a greenfield opportunity as you could have in drug development. The regulators, as I've said earlier, are highly incentivized to solve this problem with something because they have nothing to offer these patients. But once we are in place and this drug is approved, which.
The upstream opportunities in metastatic disease and other diseases that are anthracycline sensitive are enormous. It really could be a pipeline in a drug. So our IP, I'm switching gears. Our IP primarily consists at the moment of our orphan designation, which gives us seven years of market exclusivity post-approval in the United States. We will be filing soon for our European designation, which will give us 10 years of market exclusivity. We have additional protection as a new chemical entity, and we are currently drafting some patent applications related to our manufacturing process, which we believe contains a great deal of patentable subject matter. So we think our protection here is adequate and only getting stronger. I just want to point out a couple of folks in our management team, Dr. Silberman and Dr. Picker, our Chief Medical Officer and Chief Scientific Officer, respectively.
These are two absolute superstars in drug development. Dr. Silberman was the clinical lead on her chemotherapy drug. It was her study design that got that drug approved. We believe the same thing will happen here. That was her study design that I went through with you a moment ago. Dr. Picker, an absolutely brilliant medicinal chemist. carboplatin was his invention. That was his molecule that he developed. Another blockbuster. Dr. Picker has been responsible for all of our CMC work, solving innumerable problems. These drugs are very difficult to manufacture. It's a very complicated process. We have streamlined that process and in that and in the efforts to do so, we believe that we have, as I said a moment ago, created an enormous amount of patentable subject matter. On our board of directors, a very strong group as well.
I'll just point out our most recent addition, Amy Mahery. She comes to us, as the Chief Commercial Officer at Roivant, a $9 billion biotech company. So, what is she doing, in a tiny little company like this? Well, the answer is that she knows the company, because we have a chemotherapy drug on our hands. I love this slide, and why? Because it's all checkmarks and it really gives you in one slide, a snapshot of what I believe, is our excellent execution of this program, starting, a while ago with our orphan designation, our fast-track designation, our patient dosing starting, expanding the trial to Europe successfully in several countries there, enrollment of our 200th patient in September of 2023, and completion of enrollment just a few months later in September of 2024. That was 50 patients, between October, excuse me, and, January of 2024.
So really remarkable uptick in enrollment, which we think is a very positive sign, demonstrating that these physicians and their patients believe that this drug is going somewhere. The last milestone here is the best one of all, and it's relatively soon. That is top-line results from this study. Again, this is a potentially pivotal study of next year. So as a summary, again, we are developing a treatment for glioblastoma. It is a unique drug, but not a unique class of drugs. It is among the most trusted class of drugs in the world, used in millions of doses every day around the world. It was developed at the MD Anderson Cancer Center, specifically optimized to cross the blood-brain barrier and treat glioblastoma. It was the subject of a successful phase I study.
We now have a fully enrolled, potentially pivotal study with an approval endpoint that is expected to read in approximately a year. We've got a great management team, and you can see our financial summary there on the right. We basically have everything that we need, save some additional cash, to get this job done and bring this drug over the finish line early next year. So that is CNS Pharma, in a quick summary. I appreciate your attention and would love to answer your questions.
Wonderful, John. John, great presentation. Your enthusiasm is really contagious. So we're going to open it up to the Q&A portion. I do have a couple of questions before we do that. And while audiences are thinking of some questions?
If you would like to ask a question, John, click the button at the bottom of your screen, type in your question, and we will get to as many as time allows. So, John, you know, I'm thinking about this interim analysis that you had talked about, and then I looked to that milestone slide in the, you know, the last key milestone that's left, a game-changing milestone or the potential to be a game-changing milestone. You know, what gives you confidence with what you saw with the interim analysis, that, you know, this could translate into a successful outcome of the potentially pivotal study?
Sure, that's a great question, because we are very confident. And I would say that, you know, like anything, right, you build confidence on a strong foundation. So our initial foundation was the preclinical development of this drug.
It was designed specifically to solve the. We know that Berubicin does that. We know that this molecule is highly lipophilic and crosses the blood-brain barrier because that's what it was designed to do. We know it targets tumor tissue because that's what anthracyclines do. They target the overexpression of topoisomerase II. It's a great hypothesis, but you got to prove it out. We saw that in the phase one study. You don't see 48% or, excuse me, sorry, in Avastin-naive patients, 49% of patients receive stable disease or better. This is not a disease that ever spontaneously resolves. It just doesn't. This disease is a uniform killer and nondiscriminatory killer. So when you see that pattern change, when you see patients living longer or their disease state stabilizing or their tumor shrinkage, there's only one reason.
That is because whatever intervention you were giving them is having an effect. So we saw that, and we saw it enough to know that there was something there. It wasn't just a fluke, you know. It wasn't one patient stabilizing. It was almost half the patients on the study stabilizing. So we had a foundation to say, okay, we know this drug works. And this was our critical decision as a company, you know, in analyzing the phase 1 data. I said, look, here's what I don't want. What I don't want is a very expensive, nice-to-have study that shows us exactly what we already knew from the phase I. Don't give me 50 more patients and say, yes, it looks like it has some efficacy signal. Great. We already knew that because this disease, unless there's some efficacy, you're going to die.
It's fairly black and white, right? Then we said, okay, how do we design a study that's going to conclusively prove that? That's what we have today. 252 patients on the basis of our statistical analysis, and we had some outstanding statisticians from a couple of the leading universities in the country help us design this study along with guidance from the FDA. Now, we can't tell you what the answer will be because that's what the study is designed to do. But I can tell you that on the basis of those two layers of this foundation, both preclinical design, molecular development, and the prove-out in initial clinical data, optimism, and confidence that this study will deliver that result. The key here, I think, for investors is that, you know, we took a bold stance.
We could have done a smaller study just to prove things out, but we said, no. These patients, our investors deserve an absolutely conclusive answer to the question, does this drug treat glioblastoma safely and effectively? And that's what we've designed to do. And as I said, in all of that together, I think we have rung all of the risk out of this thing except the chemistry and biology. And when we do that, we can circle back to the very beginning of the foundation and say, yes, actually, there is very good reason to believe that that's going to break in our favor. Great.
Thanks for that, John. And just one more question. I see the Q&A button lighting up here. We have quite a few questions that have come in, but I can't help but go to your pipeline expansion opportunity slide.
One of the things that you had said just had been, sitting with me, the pipeline in a drug investor platform many times last year, and we've hosted you when you've hit significant milestones, whether it be, enrollment-related, anything with progress with the study, opening additional sites, expanding into Europe, all of that. So I'm wondering if this it seems you've built a powerful infrastructure, with respect to the oncology community, with, you know, the sites, the clinicians, the key opinion leaders, you know, and everything related to that. Is that something that could translate into your work with additional studies?
Absolutely. No question about it. Thanks for highlighting that. You know, we put a lot of time and a lot of capital into building that network.
Drug development is a process that's not just as simple as sort of sitting in a laboratory and coming up with, you know, with a molecule that works and then, you know, suddenly you have a clinical trial. That suddenly is years of work because you've got to, first of all, create the study itself, get the buy-in from regulators. Then you've got to run around the world and talk to people sites, how they're going to treat a patient. And you've got to bring them into the fold. You've got to give them, on the basis of, again, those first two layers of the foundation, confidence that what you're doing might actually work. Because, you know, remember, I mean, these are patients that are very, very sick. They are at the end of their life.
They've got basically one shot to change their fate, to extend their life expectancy. So it's a critical decision. It takes a lot for a physician to recommend something novel to these patients. And, you know, we believe that having done all of that work here with oncologists around the world, we will absolutely, you know, to borrow a tech phrase, be able to push more content through that platform in the future. Because once they have certainly, you know, confidence that this drug is safe and efficacious in this very difficult disease, the desire, you know, I would say really the urgent desire to test it in other applications. And, you know, excuse me, why is that? Because, again, this molecule is not coming out of left field. It's not some black box mechanism of action that these folks have never seen before.
They all trained medical school how to use this drug. That kind of confidence in a treating physician who's got to make those clinical decisions that I just mentioned, is critical for adoption, not just in a clinical trial, but going forward in clinical usage. So it's one of the reasons why we believe, yes, we could repurpose this in the future, and we will, but also that we believe ultimately if this drug is approved, it will very, very rapidly become the standard of care, for this disease.
Our audience, if you have a question for John, and we have quite a few that have come in already, click the Q&A button at the bottom of your screen and type in your question. I hope we can get to a lot of these.
And one of the things I want to mention to our audience, you know, before we bring them on, this is why we're doing this. This is why we're hoping, you know, participating in this forum. So I really appreciate that. So we're going to get to the questions. Okay. So our first question comes in from Don C. Why do you think the market's had a tepid reaction to the January news?
Awesome question. Thank you. Why? Well, here's why, I think. And we've talked to a lot of people about this because it's pretty puzzling. Initially it was anyways. But I think it's two pieces. Number one, you know, we have been undercapitalized from the get-go. We have never been a company that had the luxury of going out and raising $100 million and, you know, building fancy offices and hiring 200 people. There, we have five people.
Whoop, there it is. We have five people on our staff. That's it. So everything that I've talked about was done by five people. The second piece is, well, you know, why would that be the case, right? Like, why would we have such a difficult time raising capital? And I think the answer is, you know, CNS drugs. You know, before I joined this company, you know, I talked to some people that I respect a great deal. And that was sort of their take. Why are you doing this with your career? This is, you know, this is going to fail. However, again, I point back to what I believe was a very stepwise, logical foundation for my confidence that this is going to work. Now, proving that has taken years of work.
And every time we have had a successful milestone, excuse me, we have been undercapitalized. We've been out there raising money. And that overhang, I think, has weighed on the stock price, tremendously at each step. But despite that, every single time, we've just continued to meet our milestones on time, very capital-efficient and in a very capital-efficient way, and move the program forward. And that's exactly what we're going to do now. So, you know, sometimes I've said, look, the last couple of years, and I guess this is the last piece of the answer, you know, biotech has been, the basement of the broader market. Nobody has really. Biotech would be the sub-basement of the basement. Nobody likes GBM because everybody believes that this is an intractable problem. We don't believe it's intractable.
I've given you the reasons why we believe it's not and why we will have a solution. Now, you know, that said, there's no silver bullet to this, and Berubicin won't be it either. This is going to take additional effort. It's going to take combination therapeutics. It's going to take a lot of effort to continue. The ball has been at a standstill, essentially, on the field for 30 years. We believe we are going to make a material advancement toward the goal line. If the goal line is curing this disease, well, we've demonstrated once that this drug has the potential to do that and to shrink tumors and very, very few other treatment modalities have ever been able to show that. You know, I think that, frankly, the market's been wrong, and we're going to prove that next year .
Great. Our next question is Madison W. What is considered DSMB efficacy? Please expand on the criteria that the DSMB is considered.
That's a midpoint because it would not have been valid. And so their charter was relatively broad, and it essentially mandated that they review both safety and efficacy data, and use them in combination to make their decisions. So, we can't tell you, at this point, unfortunately, you know, exactly what they did or what they looked at. However, they were very closed-lipped about this. Part of the reason for that, too, is that you don't want to bias the study.
We've been at great pains to not bias the study because if FDA, at the conclusion of this, felt like we had a hint about more than we should have at the interim, and that influenced enrollment, influenced the type or quality of the patients that we were getting, they could invalidate the study and we'd have to start all over again, which would be a disaster for everyone. So, we took them, you know, at the output of their mandate, which was review both safety and efficacy in combination, and their conclusion was result that you could have. So, we know that that was not what investors wanted to hear, but it was, in fact, what we heard. And that's all we could transmit.
Great. Okay. Our next question is from Barry L. How effective is Lomustine, your competitor for GBM?
What meaning, what is the bar for approval?
Yeah, it's a great question. So, the short answer is not very. It does have some improvement, in overall survival, but it's pretty limited. You know, I think it might be, a month or two, if that, in most cases. But here's the kicker. So the reason that we use Lomustine is essentially, a single study, conducted in, 2015 by, Dr. Weller in Zurich. And he is one of the true KOLs in this space around the world. He's also one of the investigators on our study. And that paper, while seminal and important, had one very, very and back then, they included in the definition of GBM, patients that would now be classified as having an astrocytoma. Astrocytoma is another type of brain tumor. It's very serious.
You don't want any brain tumors, but it is nowhere near as serious, or with the prognosis that GBM patients have. But back then, you know, imaging and diagnostics could not distinguish the two. However, today, they are distinguishable, and astrocytomas are listed as another high-grade glioma, but glioblastoma is in its own class, minus those patients. Now, what does that mean for Lomustine as a competitor? Well, the only reason, think about it this way. The only reason that Lomustine rose to prominence as the unapproved standard of care is based on a study that included patients with an easier-to-treat disease. We have eliminated all of those patients now. The only patients that we have are true, no easier-to-treat astrocytoma.
So the upshot of that, we believe, is that Lomustine is going to look even worse after this study than it already is, and Berubicin is going to look better. You know, we believe and there is no magic number. FDA doesn't tell you, you know, show us a, you know, a 25% improvement or a 30%. They don't do that. They want to look at everything and make their own decision. We believe that, you know, a 20% improvement in overall survival is a layup for approval in this disease. It's not what we're shooting for, obviously. We're shooting for the best that we can get, but the bar is pretty low. And again, that just speaks to our regulatory-based decision to go after second-line GBM.
Okay. I'm going to read a comment because I always think it's important for you to hear some of the feedback.
And then after the comment, I have about six people that are asking the same type of question. And given the amount of time, I'm going to try and kind of bucket it all into one question. John, large study on a relatively uncommon, horrible cancer. It seems very hopeful overall for this drug and the patients who so desperately need a better treatment option. So, Brian, thank you for that. Now, Jason, Brian, Don, and Barry, I'm going to combine your questions. So, can you talk about your efforts to secure additional capital to complete this study? Will you be looking at non-dilutive funding? Will you be looking at potential partnering? You know, what are the types of things that you're going to do in addition to accessing the capital markets?
Yeah, excellent question. And the answer is all of the above.
We are doing everything and looking everywhere for additional capital. So, we've got an NIH grant application in right now. We believe we have a good chance of that, getting that, but, you know, we'll see. We are, you know, certainly looking at potential partners. It's a bit challenging. You know, we get the question, Big Pharma interested in this? The answer is yes. We've had conversations with some Big Pharma players, you know, but when you're a year out from a conclusive answer, they generally are pretty risk-averse organizations. And so they want the answer, and they would rather pay more for a conclusive, positive answer, than try to scoop up a bargain and take a chance. They're not, you know, investors in the traditional sense.
We're obviously looking at, you know, the family offices and the fundamental investors that specialize in this space. And I can tell you, having had many of those conversations recently, you know, once we are able to get in front of folks whose business is to evaluate companies like ours, and by that, I mean, once we get past the stock price and the market cap issue, which dissuades a lot of those folks from having those discussions. But once we get past that and they discover that this tiny little company with, you know, a teeny little market cap has this huge fully enrolled once they understand, you know, the foundation that led us to do this, we have a very, very positive reaction from folks who want to get creative.
So, you know, our take on this is we will be able to raise additional capital to finish this study. It's going to take some creativity, of course, when you're trading where we are, but we believe it's possible to do. Our ace in the hole, the thing that separates us, you know, from the other couple of hundred NASDAQ biotech companies that, you know, have less than a year of cash, haven't raised much, is that we are actually close to the definitive milestone for a program like ours. You know, if we were in the middle of this thing and still enrolling patients and our costs were still going up on the study, I think we'd have a really big problem on our hands.
But our costs are actually about to start coming down, as patients roll off the study and we approach that, you know, final milestone. And that gives people a lot of confidence. I said before, you know, our job as a company, from an operations perspective, was to sweep out all the risk in what we've given you. Really pure play, with an answer coming, in the near term.
Appreciate that. And I just want to do a time check. So I know I told you we'd be about 45 minutes. Where do you have time for a few more questions? We're not losing any of the participants. They're hanging on, so.
All yours.
Okay, great. All right. So, this is another. We've got Barry, Jason, and James that I'm going to combine their questions because they're very similar.
So you talked about the phase I study. You've talked about what you've seen in that study to help you design the pivotal, potentially pivotal study. What makes you think this potentially pivotal study will be positive?
Well, I think it's, you know, I'm going to sound like a broken record, but again, I think this is critical. That's how we got to this thing. Number one, this molecule was designed to do this job. We know from the preclinical work that it's designed as effective, right? We know it aggregates those transport mechanisms. We know it inhibits the function of topoisomerase. We know all of that. Then we put it in the real world, you know, where the rubber meets the road. You introduce this drug to patients for the first time. And what do you know?
The drug performed exactly the way we thought. In fact, it performed wildly better than we thought. So, 44% of patients, Avastin- naive patients, had a, excuse me, 44% of patients overall had stable disease or better. That doesn't happen spontaneously in GBM. The only thing that happens spontaneously is they die. And so if something other than that is happening, it must be because you introduced treatment effect. If you remove Avastin, and I just say Avastin is another drug that is sometimes given in these cases, but, it has a very, serious downside, and that is once you give it, subsequent chemotherapy will be rendered ineffective. So it's kind of the last drug you should ever take in your life. It probably will be the last drug you ever take. So we don't really count it.
But when you remove the patients that had taken Avastin, that number jumps up to 49%. So more or less, one, that's a huge efficacy milestone. Two patients with tumor shrinkages up to 80%. Again, a massive milestone. And one durable, complete responder whose cancer has never returned in sort of common, you know, parlance, you'd call that a cure. We can't say that. I didn't say that, but that's, you know, I mean, he's still alive 17 years later after a, you know, disease that kills you in 12-18 months from diagnosis. So we'll count that as a win for him, and the drug as well. All of that, we believe, gives us the foundation to believe that this study is going to prove on a larger scale that this drug actually does what it was designed to do.
You know, we didn't just pull it out of a hat. Okay, it was designed to do something. We tested it in human beings. It did that. It stabilized the disease or better. And now we are testing it at a larger scale. And so, you know, that's really the foundation of our belief here.
Thanks for that, John. Our next question from Don C is, what are the global annual GBM numbers?
50,000, in the eight major markets. So definitely an orphan disease. But again, as I said, you know, temozolomide is the main drug for treating this. It's used for a few other things, but primarily brain cancer, $9 billion a year off patent for a dozen years. You know, we'll take a slice of that and consider ourselves massively victorious, so, from a financial perspective.
But I think we do much, much, much better than that for the reasons that I told you. You know, this, I mean, GBM is a very, very healthy market, sadly, for these patients because it's expensive to treat. There aren't many options. You know, when you have such a short runway, you know, it's not overstating it to say these patients lose just about anything to increase that. But beyond that, you know, the numbers that get me excited are, let's say, the metastatic breast cancer market in the United States, 45,000 cases a year, triple the GBM numbers. Anthracycline sensitive in the primary tumor, no reason to believe that them to have a tumor, which we can't else can.
So we think we've got, you know, very, very healthy market numbers, both in terms of the primary market and then our our upstream, you know, potential, as well.
Okay. I'm going to try and combine these two because we are running out of time and there's such good questions. Okay. So, why is the sample group so small when so many are affected by this disease? And if the drug is working, why does it take so long to find out if the drug works? And then I'm going to add this onto it. And I'm sorry for the long question. But if the Lomustine arm is completed early, say 8 months, would the trial stop at that point with results available before company projections?
Got it. Okay. So I'm going to.
Sorry about that, John. So I can I can unpack it for you.
No, no, no.
I got it. Okay. So the first part of the question, why is the sample size so small? I want from my perspective, and I think from our perspective, from everybody in this space's perspective, 252 patients is our opinion. The process of arriving at that number was driven first by the FDA. You know, we went to them initially with a different endpoint, and that was what's called PFS6 or progression-free survival at six months. They looked at all of our data and they said, and I quote, "We strongly recommend you modify your primary endpoint to overall survival." Now, the reason for that is that they approved one drug on the basis of PFS6 once before. That was Avastin.
Unfortunately, while it improved progression-free survival, that's disease stability, they later discovered in widespread clinical use after approval, that the drug actually had no impact on overall survival, and patients died just as quickly after taking it. No other chemotherapy was effective after taking Avastin. So, they very aggressively backed away from any other approach that is a primary endpoint because we are not in the business of outsmarting or outfoxing the FDA. We're in the business of delivering what they tell us they want. So they told us what that was. Then we went to a couple of very, you know, internationally renowned biostatisticians and asked them, "What is it going to take to prove that?" Now, that is way past my statistical abilities to explain how they did that.
But based on, you know, who they are, I will take their word for it as we did. And they said about 250 patients were what was going to be required. That's about as large a study as you would see in this disease for an approvable endpoint of overall survival. So we're fairly comfortable in the scheme of, you know, 15,000. It doesn't seem like a lot, but in the scheme of, you know, trying to find 252 of the exact type of patients that we wanted at the exact point in their disease progression and, you know, including in the investigator's brochure. So these were. I just gave you the very top line. These are very, very carefully selected patients to give us the cleanest data possible. So that's the first part. Let's see.
The second part is about the time of the study. In an answer to the last two questions, you know, we will run the study until we have the requisite number of deaths, or events, as they call it in statistics, to close the study and perform the analysis. We have all the patients right now. We have them on both arms of the study, but we have not reached the requisite number of events. Now, the bad news, of course, is that we haven't reached the requisite number of events because we can't perform the analysis. The good news is we haven't reached the requisite number of events because we don't want the patients to die. We want them to live as long as possible.
So, we believe our best estimate, based on our analysis of the patients and so on, is that in the end of this year, and we'll spend another quarter, analyzing the data and getting ready to release it. That might happen sooner. It's certainly possible, but it might happen later as well. We're not exactly sure, but I think our estimate of, you know, of that timeline, kind of last out fourth quarter, completing analysis first quarter and ready to release data in the second quarter, is pretty, it's very well underpinned by statistics and analysis of our particular patients and where they are, you know, in the treatment. But, you know, we've had a lot of patients on this study, doing a lot of cycles of Berubicin. And we're very happy about that.
So, as frustrating as it is from a capital perspective, and from a, you know, business perspective, you know, we're rooting for these folks to keep taking Berubicin and stay alive.
Excellent. I'm looking at the time. We're going to have to have you back, I think, for an ask the CEO segment because there are so many questions still left we had while they're on. So they could be current investors. They could be potential future investors. My last question from you, John, is to those that are watching today, why do you think an investor should stay an investor, or why do you think a future investor should invest in CNS Pharma right now?
Sure. So, to the current investors, I would say thank you for your fortitude. I know this has been tough.
It's been tough on all of us, but, you know, take solace in the fact that we have done exactly what we told you we were going to do to ultimately create value, which is by getting this drug approved. And we think that that is a near-term opportunity, at least as things are measured in the drug development world. This is not five years from now. This is next year. We're going to have data. And we believe, for all the reasons I've indicated here, that that's going to be positive. In terms of why, you know, become an investor right now, look, the stock, I I mean, you know, you're not supposed to say this, but come on. It's look where it's trading. It's pretty cheap.
I mean, you know, this is going to act between the reality of what we're doing and the perception in the market of our opportunity and what we're doing. I think we're blown off by a lot of people, as I said earlier, simply because we are in the subbasement of the basement of the market. You know, nobody has liked biotech for a long time, and nobody likes GBM ever. We think we've got a little bit different approach. We think the stock is dramatically undervalued for what we're doing and where we are. And, you know, it's trading at option prices. This is a multi-billion-dollar opportunity, and that's not blowing smoke. You can just look at the data for Temozolomide, and it's quite obvious. So, we think we're chasing something very exciting here.
I've given you the foundational reasons why we're optimistic and confident that we're going to have the right answer here. And maybe most importantly, because nobody likes to sit around, we're going to have that for you, in the near term. So a bet on CNS now is a bet that you'll know whether you were right or wrong. And we believe, you'd be right, you know, in less than a year. So, I think it's a very good opportunity. It offers lots of return, you know, to knowledgeable investors as well because, you know, our job is to eliminate the risk of this thing and give you the pure play on this molecule that's very exciting. And I think we've done that. So now we just have to see it through, and bring you the answer.
Great job.
I feel like every time with all of your energy and enthusiasm and passion, when you finish, I always want to clap. But great. Great. Great job. This does conclude our virtual investor lunch break featuring CNS Pharma. I really want to thank everyone for staying on, for a little bit longer than we expected. A huge thank you to John for joining us today. And again, to our audience for your participation, your great questions, as always. I'm sorry we didn't get to all of them. As a reminder, CNS Pharma trades on NASDAQ under the ticker CNSP.
If you like what you saw today, I encourage you to visit the CNS Pharma website at cnspharma.com for more information on the company, to sign up and follow the company and receive their alerts, as well as follow their social channels, virtualinvestorco.com, for a replay of today's event, as well as our latest segments and event calendar. And with that, I wish everyone a great rest of your day.
Thank you.