time, I'd like to remind our listeners that remarks made during this webcast may state management's intentions, beliefs, expectations, or future projections, and these are forward-looking statements that involve risks and uncertainties. Forward-looking statements on this call are made pursuant to the safe harbor provisions of the federal securities laws and are based on CNS Pharmaceuticals' current expectations, and actual results could differ materially. As a result, you should not place undue reliance on any forward-looking statements. Some of the factors that could cause actual results to differ materially from these contemplated by such forward-looking statements are discussed in the periodic reports, CNS Pharmaceuticals' files with the Securities and Exchange Commission. These documents are available in the investor section of the company's website and on the Securities and Exchange Commission's website, and we encourage you to review these documents carefully. Okay, so joining us on the webcast from the CNS Pharma team are John Climaco. He is Chief Executive Officer. Dr. Sandra Silberman, she is Chief Medical Officer, and Zena Muzyczenko, Vice President of Clinical Operations. For today's event, we will begin with introductions and then move into the overview of CNS Pharmaceuticals. We will then cover GBM, the Patient Journey and Unmet Need, the blood-brain barrier and overcoming the significant challenge, berubicin, a novel anthracycline designed to cross the blood-brain barrier, and berubicin, clinical data and path to potential approval. We'll then move to TPI 287, a novel blood-brain barrier permeable abeo taxane and CNS Pharma position for a transformational 2025. So for this event, we are also very fortunate to be joined by key opinion leaders in the space of GBM. We have Professor Dr. Michael Weller. He is Director of Department of Neurology, University Hospital Zurich, Switzerland. Dr. Samuel Goldlust, he is board-certified and fellowship-trained neuro-oncologist with St. Luke's Cancer Institute, and Dr. Erin Dunbar, founding physician of the Brain Tumor Center and Director of Neuro-Oncology at Piedmont Atlanta Hospital. So we'd like to welcome all of you. So to set the stage for our audience, would each of you please provide an overview of your background and expertise? Professor Weller, we'll start with you. Yes, thank you for the introduction. So I'm a neurologist by training. Actually, I come from Germany, but moved to Switzerland in 2008 to lead the Department of Neurology there. And when I have time, I tend to devote my time to neuro-oncology. Obviously, there are other tasks that we have to do, and we have a focus on clinical trial conduct, mostly through the European Organization for Research and Treatment of Cancer. And we also have a laboratory where we try to establish new treatments. Dr. Goldlust, on to you. Sure. Thank you for having me here today. I appreciate the opportunity to talk. I am a neuro-oncologist by training, originally a neurologist. I also run the research department and the Vice President of Research at St. Luke's Cancer Institute, and I also see patients with primary and secondary brain tumors and write and conduct clinical trials primarily for glioblastoma. Great. Thank you. And Dr. Dunbar, on to you. Hi, thank you so much. I'm based out of Atlanta, Georgia. I'm a neuro-oncologist as well as a neuro-palliative care doctor, and I help brain, skull-base, and spine tumors with a primary metastatic. I'm a clinical trialist as a focus of my practice. We have a 28-hospital-based municipal practice, Brain Tumor Center, and really one of the things we do is partner with the NIH and other major consortiums, industry, and pharma to be the leading edge of the most promising drugs for unmet needs. Thank you. Wonderful. Thank you so much, Dr. Dunbar. For our participants, if you are not speaking, if we can, if you can go on mute, that would be helpful for everyone to hear. It is now my pleasure to turn the webcast over to John Climaco, CEO of CNS Pharma. Thanks, Jenene, and let me first say thank you to our physician researchers. It's really an honor both to work with all of these individuals, but also to have them take time out of their busy clinical and research schedules to be here with us. I think it really speaks to their dedication to this space as well as advancing what we believe will be a potentially game-changing treatment for the space, so CNS Pharma is a specialty oncology company. We are dedicated to neuro-oncology. We have two programs right now. One, berubicin, which is a novel anthracycline that crosses the blood-brain barrier. It's the first drug of its kind to do so. We have now a fully enrolled, potentially pivotal study that is scheduled to read primary analysis data in the first half of next year, so we're quite excited about that. We've been working on that trial for a number of years. We're going to spend a lot of time talking about it today. Very exciting drug in addition to being the first anthracycline demonstrated to cross the blood-brain barrier. It also appears to be the first anthracycline to show no evidence of cardiotoxicity, which is really one of the limiting factors in the use of that class of drugs in oncology. The drug was developed at the MD Anderson Cancer Center, the number one cancer center in the United States, the largest cancer research center in the world. So it really has a terrific pedigree, and we are very optimistic that we're going to see some positive data next year on this drug and hopefully be on our way to an approval. We're also very excited, and we'll be talking about our second compound today, our second program, TPI 287. This is a novel blood-brain barrier permeable abeotaxane, and you'll notice a theme here. This is the first drug of its kind to cross the blood-brain barrier. So this is a class of drugs that is in widespread use in oncology for many decades, a very important cornerstone type drug. And this drug does, again, similar to berubicin, what other drugs of its kind cannot do, and that is actually penetrate the brain and demonstrate the ability to treat brain tumors. So it's been studied in over 350 patients to date in clinical therapy, excuse me, clinical trials, both as monotherapy and in combination with bevacizumab. It has its Orphan Drug Designation, its Fast Track Designation. We licensed this earlier this year, and we are moving very aggressively forward, and we'll talk about our plans for that drug later, but to put that drug into the clinic and get it out to patients as quickly as possible. Next slide, please. So just a look at where we are in our overall pipeline development. Again, berubicin is our blood-brain barrier penetrant anthracycline. It is, right now, in a fully enrolled, designed to be pivotal study that will read primary analysis data in the first half of next year. And TPI 287, recently in-licensed. We are working both with the IND process right now as well as regulators to prepare for a clinical trial of that drug, hopefully beginning next year. Next slide, please. So I'm quite proud of this slide. I think, you know, for investors, this is a very important slide because, you know, as you all know, you're not really just investing in a molecule or in a program or in a technology. You're investing in a team and its ability to execute. And I think this slide shows what we have accomplished very nicely. Very small team, very efficient. This is what happens when you stick to your knitting and you are 100% focused on your mission, which in this case to date has been seeing berubicin to approval. That is the only thing we have been working on for years, and you can see a very steady march beginning with that Orphan Drug Designation in 2020, marching out to our first patient in September of 2021. The study fully enrolled, completing enrollment in January of 2024. So very rapid enrollment for a global study of this kind, 253 patients in six countries, I believe. So really very steady progress and complete dedication on our team as well as our investigators, you know, three of our leading investigators, of course, here with us today. So we're very proud of this work. We're very excited going into next year. And I think you can see in this slide the kind of work we are capable of as a company and what you can expect from us going forward with TPI 287 and that program. Next slide, please. Okay. So yes, we're going to talk about the GBM journey. So I'm going to turn it over to our KOL clinicians. Yeah, I'm happy to start on that one. So glioblastoma is a very serious diagnosis. It can actually hit everybody. Even children or infants can have it, but there's a steady increase with age. The risk increases. That's one of the major research questions. Nobody really knows what that is. And because the population in the Western countries is getting older, we're also getting more cases of glioblastoma that can easily be predicted. Treatment is not very effective. Chemotherapy works not more than in a third of the patients. And on a population level, even in Switzerland, which is really not a poor country, we still have lost half of the patients by 12 months. And that looks worse than what you read about clinical trials, but clinical trials don't have a representative patient population. So it's really a major challenge. Dr. Dunbar, can you handle the next slide? You're on mute. Absolutely. Can you hear me now? I can. Thank you. I'm changing the view back. Excuse me. There might be technical difficulties. Perhaps Dr. Goldlust. Oh, there we go. The image dropped. I'm trying to check it out. I apologize. Oh, no worries. Dr. Goldlust, if you want to take this one, I apologize. Sure. Dr. Goldlust. You're on mute. Take away from this slide and from the next slide, which we'll see, is there are very limited treatments for glioblastoma, which contributes to what Dr. Weller mentioned about the unfortunate survival statistics. As of right now, every patient that pursues treatment tends to have an operation that can be anywhere from a biopsy and some tumors that are inoperable to what we strive for, which is called a gross total resection or the surgeon removing all of the tumor that they can see. But even if the surgeon does an excellent procedure and removes everything that he or she can see to the eye, we know that there's always infiltrating tumor cells that persist after an operation. So we have to rely on other therapies. And unfortunately, those other therapies are relatively limited. If we look at a comparable slide for lung cancer, multiple myeloma, breast cancer, this second column here of common chemotherapy drugs would have dozens of options. Unfortunately, in GBM, we really have one family of options for chemotherapy that's alkylating drugs, and depending on which country you're in, that can be temozolomide or lomustine, carmustine. Those are used in various ways over the course of the disease, which we'll see on the next slide, but in terms of traditional cytotoxic chemotherapy drugs, those are really the two mainstays that we have. Bevacizumab is also approved in the States, but we know from pivotal studies of that drug that it can help patients to live better. It can increase their progression-free survival, helps with edema and symptoms, but it doesn't help patients to live longer, but that is still used quite frequently in the States, especially for palliative reasons. Radiotherapy is offered to most patients that can tolerate it, and lastly, a relatively novel treatment called Tumor Treating Fields, which has been shown in pivotal trials to extend survival, unfortunately, likely due to the involvement of the patient in wearing a device that treats their tumor, the uptake in the States is only about 20%-30%, depending on which data set you look at. If we transition to the next slide, we can see that the various combinations of those drugs and therapies here, the big takeaway, I think, especially for the investigators we have in the meeting today, is this last bucket of clinical trials. Because we have such few options to work with, that becomes an important part of the way we care for patients, knowing the statistics and knowing that we're always on the lookout for new and promising therapies that can be helpful. Thankfully, we have two to discuss today. Next slide. Okay. I'd like to introduce the fact of why we have so few chemotherapy agents that are effective for tumors in the brain. So we have to understand the blood-brain barrier. It's incredibly selective, not permeable because of tight junctions between the epithelial cells, but it also has an active transporter mechanism. And this creates the homeostasis that we need in the brain. It keeps out poisons, keeps out toxins, but it does allow, you know, the diffusion of glucose and essential amino acids to pass through, but it restricts the passage of something that would be harmful to the brain, which is detrimental to us as oncologists because these harmful molecules are something that would treat tumors that develop in the brain. Drug delivery to the brain has been a problem and challenging and in limiting any chemotherapy, as you've seen, to be able to treat tumors in the brain. The next slide shows you all of the ways that we've tried to get things across the blood-brain barrier. Liposomal formulations, they're a little bit more lipophilic. They dissolve into the cell membrane, and sometimes they bypass the transport mechanisms, but it's not that effective. We generally have done intracerebral, intratumoral, or what's called intrathecal administration, which is administration into the cerebrospinal fluid. But that has limited application because the intratumoral, intracerebral is usually during surgery, which is a limited time, and the intrathecal is only something that will surround the brain and is not something that may get into the substance of the brain. New things that have been tried, viral vectors, neurotrophic viruses that get into the neurons that lead to the brain or ultrasound, ultrasound-mediated drug delivery where ultrasound can be used for a temporary, you know, small time-related opening of the blood-brain barrier to get chemotherapy in. So obviously, we've been looking at ways to get drugs into the brain because chemotherapy has been the mainstay of what we do in oncology systemically. So the next slide says, okay, what do we do? We find drugs that can cross the blood-brain barrier, and berubicin was one of them. And it was derived from the structure of other anthracyclines. Now, you must know that anthracyclines are the mainstay of therapy for so many different tumors that we treat, but it can't get into the brain. One of the most important things is that it gets into the brain would be a major milestone for killing these tumors because we know that in vitro, when we look at these tumors in settings where we don't have to cross the blood-brain barrier, anthracyclines are very, very effective. So the anthracycline that was developed here was based on its ability to circumvent all the transporter mechanisms and its ability to get across the blood-brain barrier. Now, the mechanism of anthracyclines are usually based on topoisomerase II, which, you know, is one of the mechanisms of preventing DNA multiplication, which allows the cell to divide. But we've noted that in cellular assays, berubicin is actually more potent. And we've actually also noted that resistance, which is upregulation of these transporter proteins, berubicin is more active. So we've looked at that in preclinical models. The next slide shows just one example of that where we have a mouse with orthotopic, meaning these are brain tumors that are developing in these animals. The control mice, you know, received no medication. The other mice received berubicin, and there was a 33% increase in the ability of these mice to survive. We knew that this drug crossed the blood-brain barrier and not only that, was effective in treating tumors that were in the brain. The next slide is what we did in humans. The first in-human trial was a dose escalation trial, which is a standard escalation that we do in oncology using a small dose first and then escalating that dose into patients that we think, especially in oncology, that will benefit from this. So the dose that we used was based on animal models, and it was given IV over two hours, but every three days, consecutive days over 21 days. So doses were escalated until we got to what's called a dose-limiting toxicity. And that's when we realized that there were, you know, significant activity at doses, you know, at those doses that we were determining were the maximum tolerated dose. Now, the patients that were enrolled on this trial, there were 35 patients enrolled. All of them had primary CNS tumors. But the fact is that these patients had had a median of five prior therapies, meaning they had been subjected to, you know, a number of different treatments that were ineffective and they were progressing when they went on this trial. And 71% of these patients had at least four prior therapies. So the next slide shows you that even though they had that many prior therapies, there were significant benefits to this drug being delivered to these patients. 44% had significant benefit. There were two responses that we saw, with one being almost 80% of tumor shrinkage, which is really important because one had 100% tumor shrinkage, and that's considered a complete response, and that patient is still alive 17 years later. So we also noted that this was an anthracycline. It had its typical side effects, but it had nothing that was extraordinary. It was well tolerated and, you know, a safety profile that showed this was an anthracycline. It had no neurological side effects, and it actually did affect the tumors that were in the brain. So this was the first anthracycline that we could demonstrate in a human trial that was effective in brain tumors. So the next slide, I think, is what we'd like to discuss about this clinical trial and what a first-in-human trial could mean, you know, to a clinician and to an investigator. Thank you, Sandra. That was a great overview. So let me ask our physician guests some questions about this because obviously for our company, this is the data we built the company around. We're extremely excited about seeing that. It was the rationale for starting the company and for all the work that we've done. But let's start with you, Dr. Dunbar. What is your take on that data if we're looking back and just looking at the first-in-human study and the preclinical information about berubicin? Yeah, first of all, I want to apologize. I was speaking of, you know, unmet need. I actually jumped off the phone and would technically offer a minute because I was having a glioblastoma patient having a seizure in my office, so please forgive me for that delay, but that's real life of what we deal with, so I want to hit back on how phenomenal this experience was. I'm a medical oncologist by training, and in every single curative-intent tumor, you have to have an anthracycline, and that is incredibly important, and one of the barriers to anthracycline was that they don't get across the blood-brain barrier or they were too toxic, too toxic to the nervous system, the heart, et cetera. When I heard about this, I begged to be a part of it because I really want to help people live their best, longest life. Onboarding this trial was really incredible. We got to be the first to put the first many, many patients on this trial. I saw immediate changes on this scan. I could see what we believed was tumor kill in the first scan or two. In fact, that pseudo-progression that we want to see, we want to see a tumor, you know, opening up a can of whoop-ass, so to speak, right? So you want to see that. We were able to give steroids and after protocol amendments and other things to calm down that process of the immune system and the brain and the healing of the brain and the getting away the cellular garbage of the dead and dying tumors. We could clearly see a response, single agent, no doubt about it. The medication was incredibly well tolerated. Again, as a veteran oncologist, bone marrow transplant trained, you name it, I was ready for Armageddon. I was ready, braced for a really hard hit to the patient. They did incredibly well on this. Even having that evidence-based hope that I could see scans change quickly, they seem to be good changes in the signs of tumor kill and treatment response. The patient had a safe and tolerable treatment that was outpatient, was, you know, was good for their quality of life and their family's quality of life, gave me that evidence-based hope to keep on going. By the completion of our trial, we had some really long-term responders. And importantly, and this is my last point before I turn it over to my colleagues, is when we look at overall survival, when we look at progression-free or next-to-treatment survival, we want to see our people doing well even beyond progression. So for the patients on my panel that did ultimately need another treatment chapter or more than one treatment chapter, they kept on doing well on those other treatments and treatment chapters. They were not like crashing and going to hospice as soon as they no longer were a candidate for berubicin. These people went on to other clinical trials, other treatments, and lived well beyond what I thought they would. So those are the comments that I wanted to share with you guys. I can't wait to see this drug move forward. Thank you. Oh, sorry. I didn't mean to interrupt you. No, yeah. Who would like to be the next to share their thoughts? Yeah. Really appreciate that, Dr. Dunbar. You know, I say oftentimes when we're talking to investors that, you know, it's important for people to understand that, you know, the rubber meets the road when you have a clinician in an exam room with a patient deciding what is going to be the next step in their treatment for this very serious uniformly fatal disease. And, you know, we're not just a collection of data. We're not just a molecule. We're not just a bunch of financial reports. We're actually in the business of trying to extend people's lives. And I love hearing stories like that because that's what we're trying to do here. It actually tells us that, you know, in addition to the aggregate of the data that we see, you know, on an individual basis in those important conversations where this drug is actually designed for, really making a difference. I agree with you. I'll tell you that we had people coming from all around the country to be a part of this. That tells me that other clinicians recognized the science. We would call, we would talk, and patients would fly and even get apartments here because, you know, to be able to be a part of it. We had kids that were, one of my kids was in a fraternity at the University of Georgia. If you're well enough to be in a fraternity at the University of Georgia, that tells you that this drug is doable, right? Thank you. Thank you. Thank you. So Dr. Goldlust, you know, can you give us your thoughts? I know this is a little bit of a speculative question, but on, you know, how this might translate going forward, how, you know, what sort of are your thoughts when you look at the, you know, the phase I data and what we know conclusively about berubicin, you know, what do you think going forward? Sure. So if we think back to the slides we looked at with available therapies, it comes with the caveat that only 30% or so of GBM patients have the molecular signature that would predict response to the chemotherapy drugs that we have, lomustine and temozolomide. So it leaves us with 70% of patients or so that will likely derive benefit from surgery and from radiation, but with no chemotherapy backbone to add to that benefit. There are, in other types of cancers, you know, the sort of cytotoxic backbone of therapy was developed decades ago. And in the decades since, oncologists have been trying to refine that backbone, add interesting therapies like immunotherapies, cellular therapies, et cetera. But they still do have that backbone of treatment that everyone responds to to some extent. And GBM, we don't have that. So, I think the recurrent data will, of course, be interesting when it reads out for this particular study, but I think it also opens up an opportunity for use earlier in the disease for patients that don't have a chemotherapy option at diagnosis that we think is going to be effective. So, I think that there, you know, depending on what the data shows us, there are a few different opportunities, both newly diagnosed disease and a recurrent disease where I could conceivably see this fitting in given the lack of other options at present. Thank you. Sure. It's, you know, you told me once, you sort of crystallized it for me perfectly. You said, you know, we're still waiting for a one-size-fits-all or really even a one-size-fits-most solution for these patients, which is pretty remarkable in almost now 2025. So, you know, that's to me really what I love about this project and this drug is that, you know, it may not be as sexy as immuno-oncology, but it steps back and says, you know, what do clinicians who are actually treating patients like yourselves need every day for most patients, not just at a select, you know, institution, one or two in a huge country, you know, that like ours that can handle, you know, very specialized individual, personalized care, but a solution that could actually make a difference for even most patients, let alone all patients. A patient actually, I gave them the same discussion that you and I had, and they summed it up even much better than you and I did and said that you have to have a high school diploma before you get your PhD. So I think we're sort of lacking that high school diploma in GBM at this point for a lot of patients. And I think that was very well said on this gentleman's part. That's perfect. Professor Weller, can you, you know, give your perspective, you know, on what a drug like this could mean going forward and what, you know, in Europe, I mean, you know, what is the scope of the need here? I think that maybe you somehow cited me when you said this is not a sexy drug. That was my first response to the program, right? The problem is what do you do with all the sexy drugs if they don't work? So I think that anthracycline in principle are a very powerful agent and it has been summarized before that the major issue so far in the brain was getting it there. So with that, absolutely, I agree. And I think we have to come to terms with the fact that targeted therapy doesn't work in glioblastoma because the pathways are too redundant. So I think we're moving back to dirtier drugs or drugs that have a broader range of activity. Of course, it's always nice to see single responses, but I mean, you did the right thing to move to a randomized trial very early on because that's the only way we make sure that we're not disappointed again afterwards. I think it's also important to note that the bar is not high to get a positive trial in the sense that lomustine is not a good standard of care. It is a standard of care by convention, and it doesn't work in at least half of the patients. So there is, I think, justified hope. If I look into the future, I would still think it would be nice if we could identify a signature that allows us to predict who has benefit from the drug and who doesn't, because it's unlikely to work in everybody. That never happened so far in glioblastoma. The two other paths forward that I see is obviously combination, because in many cases, combinations have been established as a standard of care. I would also absolutely agree with Dr. Goldlust that the situation in the newly diagnosed setting needs to be explored, maybe with a focus on unmethylated patients that derive no benefit from temozolomide. I'll stop here. Thank you. A lot of great thoughts there. I guess I would say, you know, on behalf of the company, thank you for recognizing, you know, our path and toward a randomized controlled trial. You know, there was a lot of very aggressive debate internally, as I've said before in some of these meetings, that, you know, perhaps this was too aggressive an approach. You know, we ultimately decided as a team that the data, you know, to date supported an aggressive approach. We did not want a, what I sometimes call a nice-to-have, small trial confirming the efficacy that we already saw from the phase I. We wanted to prove conclusively what we believe we already know, which is that this drug works. The only way to do that was a large randomized controlled study that we did. The other thing I think was interesting since our control arm is lomustine and you wrote, you know, the benchmark paper on lomustine, I think, you know, it's telling to hear you acknowledge what we all know, that it's not a great standard. And I think we can do a lot better with this drug. So let's see. I think we're going to move on now. And we're going to turn it over to Zena Muzyczenko, our Vice President of Clinical Operations, who, if there's an unsung hero in the berubicin study, it would definitely be Zena. We could not do this work without her. So Zena, you want to talk to us about our clinical network and what you've built and what we're doing with it? Thank you, John. I would be absolutely happy to. So I think it's no secret that, you know, from the beginning, we knew we wanted to have a significant presence in the CNS tumor space. And in order to do that, we had to build a network to have that presence and to help the patients who were suffering from this terrible disease. So this really was a grassroots effort. Everything we did, it was deliberate. Everything we did had a purpose. And so with everything that we did to establish this playbook, we knew that we were going to use it not just for this study, but for the future clinical trials and for pipeline advancements within our company. We built this relationship with the key opinion leaders, with the vendors, and with the sites really from the ground up. In order to do this, you know, we had to have a lot of outreach. We had a lot of relationship building. We had to do a lot of research of who were the best investigators, who were the best institutions, and who were going to be the highest enrolling sites. We know we didn't build this network for today. We built it for tomorrow because we are committed to this disease. We are committed to this space, and we are committed to the patients and ultimately finding something to help them, as you just heard from our panel. You'll also see later in this presentation how this strategy has prepared us for ultimately a seamless transition to get our next asset, which is TPI 287, up and running. This is an asset we've been evaluating and investigating for our pipeline for quite some time. It's not something we just pulled out of the air. We knew that we had something that we could plug into this network that we've built. We knew we needed something to put into this clinical engine, and this is an asset that a lot of our team was really familiar with. We knew the structure, and so with all of that groundwork already done, we have this now network that's really second to none, and because of this, because of the time that we've spent in building this network, we really are poised and ready for success. We're really ready to tackle TPI 287 and to advance berubicin and to really just set ourselves up for success. All I have to say is that was an incredible introduction to what I think is an incredible team. We've worked together now for several years. I have to say that dedication in this team is second to none, and expertise has been just the thing that has moved us over the top, so as John said, we moved into a potential pivotal trial. Rather than doing a small trial to establish the, you know, the drug's activity, we knew that there were patients that were dying, and why not look at it and definitively establish whether this drug has activity? And so what we did was we generated this trial, which was a randomized two-to-one trial against lomustine. Again, you know, the two-to-one was because we felt that more people would want to go on to an experimental arm. I do have to say that our beginning enrollment, and thank you, Dr. Dunbar, we love you because the beginning enrollment was during COVID, and we had no idea whether we could get patients because of the stigma and the, you know, the issue of getting patients to our clinics. Dr. Dunbar, you set the stage and got us into our first patients that were dosed. We are fully enrolled in terms of our sample size. Our statisticians have said, this is what we need to be able to show that there is an improved overall survival of our drug over lomustine. It's overall survival. That is the only way that this drug will be approved by the FDA and by the EMA. We're both regulatory agencies are working with us at this point. So it would be, you know, an approval in both Western Europe as well as the United States. We have 45 centers in five countries. We randomized 252 patients. Again, it was two-to-one. But what we did was, first of all, we made sure that these patients were IDH1 w ild-t ype. 2021, during, you know, the institution of this protocol, it came out that IDH-w ild-t ype were the only grade four glioblastomas. So we made sure that everyone enrolled on this trial is IDH-w ild-t ype. And that's number one. So we have a population of patients that are equivalent. The other thing is we don't know the impact of MGMT promoter methylation. We know that it has an impact on temozolomide, but we don't know that it, you know, it may have an impact on, first of all, prognosis, but second of all, the mechanism of action of our drug, which we think has nothing to do with what MGMT promoter methylation causes. So we have stratified our patient population and have an equivalent number of patients with MGMT unmethylated on both arms. It's 39%. It's absolutely equivalent. So when we do the analysis on this study, we know that we're comparing it to equally prognostic patients as well as grade four glioblastoma patients. The other thing that we did was we developed an independent safety monitoring board. And what they did was they allowed the integrity of the data and the ability of us to go forward with a futility analysis around the middle of the study to make sure that our drug was still having the efficacy, still having the safety, and was comparable to what we were seeing with lomustine. And this was independent. And it was important because what people may not know is the company is blinded. Our investigators are blinded to the total data from the study. So there's no way that we can, you know, establish that we have this much efficacy. And this is why we haven't reported on that, but we've been willing to wait to our outcome, which is overall survival for the patient population, which will be ultimately something that we can register. So the next slide is talking about our futility analysis. The rationale for that, as I explained, was to make sure that we were conducting the trial with integrity and that patients were receiving the best possible care compared to a control arm, and we received that data in the, you know, in the middle of the trial, and they made informed decisions not just about the safety, but they made informed decisions about looking at the efficacy. They were the only ones that were informed about the efficacy, and that included overall safety as well as the secondary endpoints, which we've included in the trial, which is progression-free survival and response rates, and so when they decided, it was a year ago that they came back and they said, we've reviewed the data. The data from your trial, you know, indicate that your trial should go on without modification, which said to the company, we are at least providing some benefit to the patients that are on the trial. The safety is manageable, and the effectiveness is something that we would need to be looking at in the future. We think that that meant that we had an effectiveness that would show without modification of the conduct of the trial. We continued with the trial. Next slide, I think, is what our next major milestones are. Again, we developed this trial as a registration trial. We didn't want to do any small trials. We figured that this was a drug that had efficacy, that had safety. We haven't, you know, enrolled the complete number of patients we need for the sample size to evaluate the number of events. We are continuing with the number of patients that are on the trial. Our primary analysis will be based on overall survival, and we will be discussing with the FDA whether or not that primary analysis meets, you know, their standards for an approval at this time. Although we will continue with the number of patients on the trial to complete the sample size, but we think that with the primary analysis, we will achieve that benefit, so that we will be reading out in the first half of 2025. We've already started compiling the data in the electronic databases and working with our vendors to make sure that we have clear data, quality data, and that we can present that effectively to show that we've had that, you know, that benefit. Next. John, you're on mute. Sorry about that. I was complimenting you. Thank you. And great work. Beautiful design. I, you know, I'm in love with this study and optimistic that we're going to have not just interesting, important results, but definitive results, which is what we wanted. So Dr. Goldlust, let me ask you, what's your takeaway from our interim analysis? And And what implications do you see sort of going forward? I think it's certainly promising. Unfortunately, a lot of GBM studies are stopped before they reach the point that this study has for futility. I think those are great signs. I think in terms of the potential impact, like we've talked about, there's no standard of care for recurrent GBM at this point. There are therapies that are used, Avastin, which we touched on, Tumor Treating Fields, which we touched on, but there's never been a drug to extend survival in recurrence that we know of. This would have an immediate impact. I think that if this drug were approved, it would be the lone competitor really for that space and what to offer people at recurrence in, especially given that as far as we know, it's relatively agnostic to particular markers and may in fact help all comers, which of course we'll find out soon enough. I think the uptake in the neuro-oncology community would be very swift and very impactful and without really any sound competition in the space. Thank you. Dr. Dunbar, what does a successful outcome for this trial look like in your eyes? I think you're on mute. I would first share a concurrence with everything that Dr. Goldlust said, that it's agnostic, that it's gone this far in trials. I want to add that there's been no, you know, safety or dosing or warnings. You know, a lot of the clinical trials I've had the privilege of being a part of, you know, we're already doing major dose adjustments and toxicity tolerance education and, you know, all of this stuff just to try to like make the drug tolerable to continue going forward, and this has really been, you know, again, just really, really free of those things, so I think a successful trial going forward, I think must continue to be done and survival absolutely should be done. I think that when we're creating a design because we saw early cell kill, because we want to kill tumor, that provision of allowing certain amounts of steroids or maybe if we think it's treatment effect, radiation necrosis, amounts of short-term bevacizumab. I think that one of the things that excites me about this is when we look at anthracycline survival benefit in every other tumor tissue we've ever had, that it actually is good for combinatorial therapy. And so I see this as being something that, especially because it's agnostic for, you know, one particular tumor marker, is well tolerated, is an anthracycline, that it might be that generations of this, that this becomes a foundational step that then future clinical trials are building on bevacizumab plus, or a bevacizumab and a taxane, bevacizumab, excuse me, I'm going to say, berubicin and a taxane, et cetera, et cetera. So those would just be some additional pearls. I'd like to hear what Dr. Weller thinks. First, we have to hit the bar, but I think we're all fairly optimistic that in MGMT unmethylated patients, we should be able to hit the bar from what we know about the disease. And then, yeah, I also think really, we all know it's not going to change so much. The patients will still die. It will remain a lethal disease. And that's why I think looking into possible combination partners with non-overlapping toxicity would be great. And that's then maybe where suddenly also preclinical new ideas, new studies on a very old drug become interesting. Absolutely. Any other thoughts on this trial or the design of the trial? I'll just make another comment that I think it is a scalable drug in trial. And I think it's got a lot of external generalizability to multiple care environments, not just academic, but could be municipal and community, even rural. And I think that it also can be done in multiple healthcare systems around the world. So I think the scalability and generalizability of it is very important. Yeah, absolutely. And I sort of, you know, touched on that earlier. It is one of the things that interests me the most about this drug is that, you know, the ability to deploy berubicin therapy is in many ways unlimited. It's not going to be dependent on a particularly sophisticated, you know, cancer center or something like that because this is a, you know, as Dr. Weller said, it's an old class of drugs. It's been around for a long time. We know how to use this drug. You know, I often say there's not an oncologist in the world that hasn't been trained on anthracyclines in medical school. They've been around forever. So I think that bodes really well for the utility of this drug. You know, one question I had, you know, is, you know, I'd be curious for each of you, but, you know, Dr. Goldlust, what do you think about the potential for a drug like this in metastatic disease? Metastatic disease in terms of gliomas or? In terms of, you know, as we look to the future, you know, each of you have sort of hinted about, you know, different things that we might do with a drug like this in the future in terms of it being part of combination therapy or additional studies to find, you know, more utility from this drug or where we place it. But one of the things that we've thought about and talked about and are often asked about is, you know, there's lots of different cancers, you know, in the body that have a known metastatic pathway to the brain. And those patients face similar difficulties as the patients that have a primary brain cancer diagnosis. So I'm curious what, you know, about your thoughts in terms of, you know, if we're sort of, you know, future casting about what we might do with a drug like this if it's successful, you know, what do you think about something like that? Sure. I think it's an excellent point. I think there's sort of low-hanging fruit in terms of how else we might, if we can see benefit here else, we might use it. I think, one, to Dr. Dunbar's point, in combination therapy for gliomas or GBM specifically, I think that makes a lot of sense scientifically but as you pointed out, brain metastases from solid tumors are a huge unmet need in terms of novel therapies. Radiation has its role, and we do know that some targeted immunotherapies in other cancers can have more success in treating brain metastases than they do in gliomas like GBM, but those patients almost universally, unfortunately, still die of their brain disease related to their primary tumor. So there comes a point in everyone's journey along that pathway where they need salvage therapy for brain metastases when radiation and other treatments have run their course. I think it's a very rational next step in that, you know, there's for many of the cancers that metastasize to the brain, there's probably a tenfold number of patients with those particular primary tumors, which are quite common compared to GBM. So I think once we see that signal in GBM, I think there's a few different directions we could go, but that's a very sensible one. John, I'd add to that that one thing that, you know, I would dream with Sandy and Dina about is brain metastasis because ten times more common, how well tolerated this drug was, how it was easier than a lot of other regimens that these metastatic patients had already endured. You know, they would be like, "Oh, this is a piece of cake compared to what they've done." But not only brain metastasis, but if we think about its tolerability profile in terms of less cardiotoxicity, less neuropathy, less GI toxicity, I guess one of the further dreams I would have would be, does this actually compete head-to-head with existing systemic therapy anthracycline as a better anthracycline, either even in earlier upfront, you know, adjuvant or advanced disease tumors that need anthracycline, which are, you know, so many different histology types. But who knows? But I think that those were things that I've dreamt about. So can I just add that, you know, as of course, I've been the medical monitor and I've overseen the safety of this entire study. And what we've done is echocardiograms on every patient as well as ECGs, but also troponins, which are very sensitive indicators of cardiotoxicity. And even on patients who have been, I think, 23 cycles has been the longest patient, we have not seen any cardiotoxicity. So we're very hopeful that we are minimizing what is probably the greatest toxicity that we see with anthracyclines and the limiting toxicity that we see. You know, so again, Erin, as you're saying, this could be an important aspect of systemic treatment preventing brain metastases because it's no longer a, you know, an area where the brain, where the tumors can have a sanctuary. So it could be interesting. Absolutely. Well, I love that, Dr. Dunbar. This is, you know, we like to think big and we like to think about this being sort of a dream next-gen anthracycline that can do a lot of things that other anthracyclines cannot do. And of course, to me, the, you know, the logical places to start investigating and push for this drug, assuming we get the results we expect from this trial, are, you know, as a non-cardio toxic blood-brain barrier penetrant anthracycline, that certainly speaks, I think, to doing things that, you know, doxorubicin, daunorubicin, et cetera, cannot do. So we think the future is very, very bright for this drug. And again, just thank all of you for your work in helping us make this a reality. So let's switch gears now. We're going to talk about something that you will hear some similar themes in terms of an old class of drugs that possibly now can do something very different and very special. So this is TPI 287. This is our second program. And I will let Dr. Silberman talk about this and its history and where we're going with it. So, Sandra, take it away. Oh, absolutely. TPI 287 was developed because it was looked at as a class of chemotherapy that can bind to microtubules, but also is not a substrate for P-glycoprotein. So this is a common theme for what we're doing here at CNS Pharmaceuticals. So paclitaxel, we know, is a very, very important drug that we use in a lot of solid tumors and has been used for over 50 years, but it does not get into the brain. I do know that there have been several studies looking at it as a liposomal formulation to try to get it into the brain as well as using ultrasound to try to open the blood-brain barrier to, you know, to say that we can get it across the brain. So of course, it's, you know, it must be an important molecule. This is a molecule that because of the what you see red encircled here, which is called the baccatin ring, which binds to the microtubules, actually binds to the microtubules quite more efficiently and the side chains, which allow it to get across the blood-brain barrier. We now have a drug that is ubiquitously used in solid tumors that now gets across the blood-brain barrier. CNS Pharmaceuticals has now optioned two drugs that get across the blood-brain barrier that are very, very effective against glioblastomas. I would like to move this over to Dr. Goldlust, who has been instrumental in developing this drug over the years. It is my pleasure to, you know, discuss it with him because it's been a pleasure doing this with him for so many years. Thank you, Sandra. So this was a planned phase 1/2 study that we ran at about five to ten institutions around the country. And what you see reported here is the phase I data. So the goal was to treat 20 or 25 patients to find the optimal dose to progress into phase II. But some of the interesting takeaways here, if we go to the next slide, you know, this phase I studies, as we know, are really designed to look at safety and toxicity. So the question is for recurrent GBM, which was this particular cohort, could this taxane in conjunction with bevacizumab or Avastin, was it safe to give to patients? That was our first question. But what we found was, although the numbers are relatively small and they have to be sort of taken with that in mind, the survival data of preliminary efficacy, as we called it in the paper, was considerably more impressive than we generally see for drugs at recurrence. We can see here the median overall survival was 13.4 months. Now, keep in mind, these are patients at recurrence. So 13.4 months, if we think back to the slides we saw at the beginning of this presentation, you know, the median survival at diagnosis is somewhere between 12 and 18 months. So this number really stood out. And keep in mind too that we found the ideal dose to progress to phase II, but the vast majority of the patients on this study actually didn't receive that ideal dose. They received somewhat less than the ideal dose. So the benefits that we're seeing here in terms of progression-free survival and overall survival, which are already impressive, if you take into account that some of them were underdosed in comparison to the dose that we now know as ideal, and moreover, the vast majority of these patients had unmethylated MGMT promoter, which, as we've touched on over the past hour or so, is a very important prognosticator for GBM patients in general, and if you just look at their overall survival, because they don't respond to typical chemotherapy drugs, they tend to not live nearly as long as patients with a methylated promoter, so this study was really enriched for patients who traditionally don't respond well to treatment. It's very exciting to keep this drug in development because everyone that's seen this data that we've presented over recent years is excited for the next phase of the drug for just the reasons that we've talked about. If we look here, this is a post-hoc analysis just comparing the TPI 287 in conjunction with Avastin, which was our particular combination, to contemporary trials ongoing of either Avastin red curve or Avastin plus a comparator drug in a different clinical trial. You can see just to give an idea of what this drug accomplished in our cohort versus other studies of Avastin or Avastin plus in contemporary cohorts, you can see the survival curves on the bottom are quite impressive in comparison to other studies at the time. And just sort of gives us that much more enthusiasm that a company like CNS has taken on this drug. And we're very excited to see the next steps based on the data we have so far. Oh, John, you're muted. Again. Thank you, Dr. Goldlust. Really appreciate that. It's terrific to have you on board after all the work that you've done on this drug. As you know, you know, we looked at over 200 different potential compounds to bring in as a second program. And we finally settled on this one as we felt it had the absolute best fit, best data, and best prospect of approval going forward. So really remarkable data from, you know, from your earlier studies. So. I just want to interject. It's not just the people at CNS, but at the recent SNO Meeting, the Society for Neuro-Oncology, and every meeting preceding that, whether it's the ASCO meeting or the SNO Meeting, the big sort of brain tumor meetings, at least 50 people come up to me and say, "What's going on with that TPI drug? We haven't seen any data in a while." And people remember it as something that stood out. There are a lot of failed trials in GBM. And by going through those 200 compounds, you almost certainly saw a lot of not very impressive data. This really stood out not just to folks in pharma, but people practicing sort of on the ground. They remember this data and they're excited to see the next steps. Yeah, that's definitely what I understand. And I know there, you know, there's no shortage of shots on goal in this field, but there's an awful lot of misses. So this one, well, you know, obviously we've spent a long time doing diligence on this and we're moving very aggressively to put this back in the clinic. So I think, you know, you can tell your colleagues that we have the pedal to the metal on this program to see it in the clinic as soon as we can. Dr. Dunbar, let me start with you. What, you know, taking a look at TPI 287 and the data from Dr. Goldlust's work, you know, what are your thoughts on a taxane like this for GBM? I'm very excited about this as a class of drugs as well. Just basically the microtubules are such an essential part of how GBM exert their, you know, their ill humors in the brain and how they maintain and function and, you know, of course divide. This is again one of those strategies that isn't just relying on an over- or underexpressed, you know, special marker chemical or, you know, things like that. I'm excited about that. The preliminary data I was also very excited about. I will share with you that as a complete outsider, I heard many of my colleagues talking about the data that's been presented thus far and wanting kind of in. To me, that's a good sign. It's passed the sniff test of a lot of the scientific minds who are looking for that evidence-based hope. What are the next things that they should be either learning about or trying to bring to their patients? What I would share with you though is, you know, for me specifically, this is a kind of trial that I would want to onboard to our 28th healthcare system. So, you know, definitely excited. Great. Professor Weller, you know, to sort of go back to your phrase about these less sexy treatments, you know, here we have a taxane, another older class of drugs. What do you think about a drug like this in terms of the treatment regimen, where it fits in, how it might be used with something like berubicin? What are your thoughts? I'm not sure it's as old as anthracyclines. Maybe it's a bit younger. I don't know. You would have to ask his story. I would say it's maybe a little bit more sexy. My comments would be regarding the development with the European hat on. Don't embark too much on marrying the drug to bevacizumab, right? Because bevacizumab is not approved anywhere here except in Switzerland, but Europe is much bigger than just Switzerland. So having a path forward, getting rid of the avastin backbone, I think would be good because also for this drug, moving forward into the newly diagnosed setting would be attractive, and here I think that's also for the U.S. relevant to see that the drug is explored on its own, and then the major issues with taxanes, of course, is peripheral neurotoxicity at least. That's an issue. I think it's really important to monitor carefully the dosing. How much can you give safely? Because you want to have an effective dose, but you need to look at the overall brain altogether. Dr. Goldlust, any additional thoughts on those? I wanted to ask Dr. Goldlust, clinically, how are you, you know, proactively or did you have a care plan to proactively try to prevent, minimize, ameliorate neuropathy? Just teach us a little bit, like what was your proactive step? I'd just love to hear that as we think about moving this drug forward. Any pearls for us? One thing I didn't touch on when we looked at the curves is the safety of the drug. The way that we chose the MTD to move on to the next phase was at higher doses. We had two cohorts above what we ultimately chose. Patients did start to develop neuropathy and neutropenia at those doses. That was key in telling us that we've reached the reasonable tolerability of a drug and we started to see toxicity that mimicked other taxanes. We did arrest the dose escalation when those started to emerge. Not in an overwhelming way. There wasn't serious toxicity, but the patients started to tell us more about it. I think we found a dose that balances efficacy without a lot of the sort of debilitating taxane-type neuropathies that we've seen with traditional drugs like Taxol or Taxotere. And I think to Dr. Weller's point, this study was conceived in an era where Avastin plus X was a very popular paradigm in designing studies. And that's since passed. But I think we can take away, you know, at least some hope. We know avastin doesn't prolong survival. And the real takeaway from this particular drug was, of course, we want to see it duplicated in further studies, but these patients were living longer than expected. And we can't chalk that up to the Avastin just knowing that Avastin doesn't have that benefit. But I think it's spot on that in the development of this drug, we need to think carefully about the role of Avastin and sort of how we see that in the development. It may make a lot of sense to design a study or a further study in which Avastin is not used for that reason. Well, thank you. And I think I would emphasize for our investors watching that, you know, what you're seeing here is probably a little slice of what actually goes on behind the scenes in terms of how we do what we do. You know, as Zena said, every decision that we make is thought out. There's a reason behind the decisions that we make. And that certainly extends very deeply into trial design. These are multifactorial problems. We're trying to get a very clean and precise end that proves definitively what we want to prove. And there's a lot of pieces that go into it. And it's really fantastic for us to have this much clinical research and intellectual firepower around the table helping us make these decisions. So you can see that, you know, our process is a thoughtful one and a careful one. It's not simply trying to chase, you know, what everyone else is doing, but in fact, being very thoughtful and careful about how we design a study based on what we know, based on what we want to do, and what is the best way to utilize, you know, the clinical network and the assets that we've built so far with berubicin. So looking forward very much so to continuing this development process and seeing some very big steps in the near term and over the course of 2025 with TPI 287. So let me just switch gears here briefly before we get to Q&A and just talk about where we are on the commercial aspect of the company because we are planning for success with berubicin. So one of the things that we are looking at is how do we take a successful drug out of this clinical trial and into the market and actual clinical use. So with that in mind, we made a very important appointment to the board of directors last year, bringing on Amy Mahery. Amy is the Chief Commercial Officer at Roivant. That's a $9 billion market cap pharmaceutical company conglomerate that, in case you are not familiar with it, but Amy has an incredible portfolio and an incredible background, and she's been instrumental in helping us think about, you know, how we want to do this. And really, as I've said from the beginning, you know, shareholders, investors should know, you know, our commercial plans are we're going to do the best thing for the patients. I always think about that first. If we start with the patients, all the other things flow from there. The best thing for the patients is to get this drug out as fast as possible, as widely as possible. And if that means that we have to do it ourselves, then we will do it ourselves. If we can find a partnership where our interests are aligned and we are delivering the most value for shareholders and the best outcome for patients, then we'll do it that way. But we are in the beginning stages right now of that planning, developing that commercial strategy, really looking across the board at all options from partnership to, you know, an outright out license to going it alone and doing this commercialization ourselves. And on that last point, I would say that, you know, investors should note, you know, neuro-oncology is not a huge field. Globally, they're just not that many call points. And so while it's a daunting task for a small company, it's not an insurmountable task. And Amy actually is quite convinced that if that turned out to be the best direction for us economically, for the shareholders, for the patients, that it would be well within our reach to go that direction. So we have a lot of confidence coming from really one of the best in the business on our board. So we are also getting ready to staff up as we expand our clinical operations. Now we'll go from one to two programs. So you can see a couple of the titles there that we're going to be bringing on board as well as some other folks. It's been great working with a very, very small team. But the fact is that, you know, we want to make sure that we are appropriately staffed to handle two programs, one which we hope will be in regulatory work with FDA and heading rapidly for the commercial market. So our milestones going forward, you can see first half of 2025, again, primary analysis for berubicin. We've got some preclinical and pediatric studies that we want to do to fill in our data package. We'll be meeting with FDA on our strategies for both berubicin and TPI 287. Transfer of the TPI 287 IND from our licensor over to us will be complete next year. We'll be finishing our protocol design and then getting ready with our key vendor contacts and our clinicians and so on. One of the huge advantages I want to say again, sort of just touching back on what Zena discussed is that, you know, we built this clinical network that enabled us to really crush it on the berubicin trial in a few years and rolling, you know, certainly one of the largest, if not the largest GBM trial globally in only three years. We built that not just to do that job, but we built it for the next job as well. We didn't build it for just today, but also for tomorrow. And tomorrow is TPI 287. And these same clinicians, you know, including our colleagues here with us today, were instrumental in building that berubicin network, are going to be helping us study TPI 287 and much more efficiently because we have worked with all these folks for years now. All of the networks are in place. All of our work with their back office staffs and their institutions are in place. So all of those things add up to efficiencies that drop directly to the bottom line, both in terms of cost and time efficiency. So we're very excited, if anything, to see a faster job on TPI 287. So next slide, please. All right. So let's go to Q&A. So I do have some here. So let me just take a look. John, I can moderate that if you'd like. Yeah, sure. Go ahead. Yeah, sure. So if you have a question, click a Q&A button at the bottom of your screen, type in your question, and we do have time for a few here. Our first question that comes in is, "Doctors, can you help us understand the key points on why you would choose an anthracycline or taxane for GBM? And what patients are the ideal candidates for each class of drug?" So anyone that. I think as we kind of touched on earlier, maybe the question came through as we were discussing. We know historically, as Dr. Silberman mentioned, that in vitro, GBM cells respond particularly well to those classes of medications. The key is that they haven't been formulated in a way that they can reach tumors in therapeutic concentration. So I don't think it would necessarily just be limited to anthracyclines and taxanes. It's just those have had a big impact in the world of oncology in general and many different tumor types. They're reasonably well tolerated, and we know they work in GBM. The key is until now, we weren't able to deliver those in a meaningful way. So with the formulation of the two drugs we talked about, that kind of leads to the rationale. Okay. Our next question is, "You mentioned that methylation status is consistent across the berubicin-lomustine groups, approximately 40% each. Do you anticipate that the methylated group should have superior outcomes per usual versus the unmethylated? Or is there a reason to think berubicin might have a beneficial effect on unmethylated patients? And will you run a subgroup analysis to further dig into this? You want me to answer that? Part of the protocol says we have some exploratory analyses, and that is because of the stratification looking at the subgroups of methylated versus unmethylated. But if you know the mechanism of why, you know, MGMT promoter methylation works to, you know, to inhibit the ability to repair the DNA, we don't believe that this is part of the mechanism of anthracyclines. So we don't think that anthracyclines or taxanes will be impacted by this. What the other thing that is very interesting is, both anthracyclines and taxanes, resistance has been noted to be upregulation of P-glycoprotein. And so we believe that even in resistant tumors, that may they be, you know, systemic or even metastatic to the brain, these will not be, you know, these will not be resistant to either of these drugs. So we do believe that these drugs will be very, very effective in multiplicity of diseases and indications. Okay. Next question, "Can you talk about the health status of a GBM patient that has had four or five prior lines of therapy and if we might see better responses in earlier stage patients? I'm happy to take that. Glioblastoma patients can be of all ages and all health statuses. Those that find clinical trials tend to be slightly healthier, but not always. When we look at a glioblastoma patient that has had several lines of therapy, they tend to have accumulated some amount of symptoms, whether we call it, you know, from the insult and injury of the tumor and treatment. But in general, based on, you know, the location of the tumor and their overall wellness, they can still be very, very fit patients. It all depends on location and a variety of factors. I will share with you that patients are being able to have less symptoms and higher quality of life and higher Karnofsky performance status measurements the further we go forward. So patients are, you know, we're definitely helping people live better and fitter even while they're dealing with this disease. As we get patients earlier in their treatment journey, they absolutely tend to be a bit fitter. But again, it tends to be what are their other health issues and where's the location of the tumor and some of the tumor dynamics. Our next question, "Given the intractable nature of GBM overall, is it fair to say that almost any improvement in OS would represent a clinically meaningful improvement in this patient population? And what would an approvable OS improvement look like for berubicin? I think it's fair to say that maybe with the exception of pancreatic cancer, the bar for OS benefit is probably set the lowest in GBM in terms of a drug to be approved in pretty much any other cancer, so I think any OS benefit that was significant would change the field quickly. Okay. I'd like to add to that, really quickly, Jenene, and one of the things is treatment toxicity. Historically, people are actually dying faster or worse because of treatment toxicity. So we think about overall survival based on their disease dynamics or the ability to treat and slow down those disease dynamics. But a huge portion of patients die because of cumulative toxicity. So if we have a drug and it seems that way that there is efficacy that could drive overall survival, and at the same time, those treatments are more tolerable, then you're getting sort of an additional mechanism of why the patient can live longer. Does that make sense, everybody? So it's efficacy of the drug and lack of cumulative toxicity or additive comorbidities of that treatment. So two reasons to help people live better. Great. I know, John, we have run out of time. I'd like to turn it back to you for closing remarks. Okay. Thank you. Well, first of all, let me just thank our physician panelists both for taking the time today out of your busy schedules, but also for the years of work on berubicin and also in Dr. Goldlust's case and TPI 287. We just simply could not do what we're doing without you. So we really appreciate it. And thanks to all the investors and shareholders who tuned in today. I hope this was helpful. It's been a great session for me. And we are looking forward to a great 2025, some fantastic news for berubicin and major advancements in our TPI 287 program. So thanks, everyone. Appreciate it and happy holidays. Thank you. Bye-bye. Thank you. This does conclude the CNS Pharma Virtual Analyst and Investor Day. You may disconnect your lines. Thank you. Thank you.