Okay, good morning, everyone, and welcome back to the BioConnect Conference. My name is Joshua Corson, and I'm an equity research associate here at H.C. Wainwright. Now I'd like to introduce our next presenter, Ron Bentsur, who is the CEO of Nuvectis, which is developing its small molecule therapeutics, NXP 800 and NXP 900 in oncology. The floor is yours.
Thank you very much.
Thank you. I want to thank H.C. Wainwright for inviting us to present here at BioConnect at this beautiful facility here in Nasdaq. I really appreciate it. My name is Ron Bentsur, and I'd like to introduce you to the Nuvectis story. Next slide, please. I will be making some forward-looking statements, so I do encourage anyone who's interested in the company to read our public disclosures, and in particular, the risk factors which appear in the 10-Q that came out for the first quarter, and also in the 10-K for 2024. Next slide, please. As was mentioned in the introduction, we're a company focused on precision medicine in oncology, so targeted therapy. We have two drugs in development. The first one's called NXP 800. The second one's called NXP 900. I'm going to talk about both in some more detail.
Another thing that's important to mention is, again, without, you know, kind of pounding our own chest or tooting our own horn, is the fact that we're a very seasoned management team. The three co-founders of the company, we've worked together on and off for close to 25 years in the industry. Next slide, please. You can see our beautiful faces here. Yeah, don't short the stock because of the faces, please. Down below, you can see the companies that we're involved with. Curex, Urogen, and Stemline. I was CEO of both Curex and Urogen and a longstanding board member at Stemline. At each one of these companies, we were able to get a drug approved. At Curex, it was a drug called Orixia, which is not for oncology, it's for dialysis patients.
The other two drugs, Jelmyto and Elzonris, are both for oncology. Very similar to what we're trying to do here, severe unmet medical needs for small patient populations. These are basically clinical programs, just to give you a sense of the scope of the clinical program. The entire clinical program for Jelmyto was around 50-55 patients. For Elzonris, it was even less than that, about 46 patients. Again, that's basically a result of the fact that you're talking about, you know, life-threatening, severe unmet medical needs in oncology where the patient populations are not enormous, and there's a true dire need to get drugs approved. There are certain discounts, if you will, that the FDA allows you to apply. One of them is you don't need massive clinical trials.
That's kind of the same approach that we're hoping to replicate here at Urogen at Nuvectis. Next slide, please. Just in terms of where we are in terms of stage of development, the first drug, NXP 800, is currently in a phase 1B program. That phase 1B program is comprised of two diseases. The first one is a very aggressive subset of ovarian cancer called, and bear with me here, called platinum-resistant ARID1A mutated ovarian cancer. These are basically patients that have either ovarian clear cell carcinoma or ovarian endometrioid carcinoma. Why these two subgroups? Because these are the two subgroups where you find the ARID1A mutation. We're looking for patients that fall under these two subcategories that have the ARID1A mutation. These happen to be very aggressive subsets. About a year of expected survival upon diagnosis.
Of course, by the time they make it into our study, it's less than that. As you can imagine, the prognosis for these patients is absolutely horrific. There's a real need to try to find something for these patients. The second disease that is ongoing, technically under an investigator-initiated program, which is not being run by us, it's being run by the Mayo Clinic, is in a disease called cholangiocarcinoma, which is cancer of the bile duct. That's being run by them. Down below is basically where we are with NXP 900. NXP 900 is currently in a phase 1A dose escalation. We're about to finish that. The next step will be the start of the phase 1B, which will encompass several arms within that same phase 1B umbrella, if you will.
There are some very exciting opportunities that we're going to be pursuing with NXP 900. I'll describe those in just a few slides. Next slide, please. Next one, please. Just to give you a sense of some of the preclinical data that was generated in ovarian cancer in models that have the ARID1A mutation. These are kind of classic ovarian clear cell models with the ARID1A mutation. You can see two different models here. These were in vivo experiments or animal experiments where we went head-to-head against platinum therapy. The reason we did that is because that is the standard of care frontline. That is the only thing that's given to these patients. The response rates frontline are very low. They're about 25-27%, relatively short-lived. Beyond that, there's really nothing available. That is where we hope to come in.
Here you can see our drug in red, that's NXP 800 versus platinum in green and versus the control in black. You can see that irrespective of whether you're looking at the right side or the left model, NXP 800 appeared to outperform platinum, which is very nice to see. There are many of these experiments that were conducted. Some of them we inherited from the licensor, which is the Institute of Cancer Research in the U.K., the equivalent of the NIH or the NCI in the U.S. Some of them were conducted by us using third parties. The data was all very consistent, suggesting that this drug could have a significant impact in this patient population. Next slide, please. This is where we are with respect to the phase 1B. Again, this is a very busy slide, so don't bother reading it.
I'll describe exactly what has transpired so far. We started the study using two doses that were given daily, 50 milligrams and 75 milligrams daily. What we saw in the very early going, and this goes back to a March 2024 press release that came out, was that in the first four patients, two received 75, the other two received 50, we saw a very nice signal, activity signal. We actually saw a partial response, and we saw stable disease. Obviously, that was very encouraging. At the same time, we also saw that out of the four patients, three had grade 4 thrombocytopenia, which is basically a lowering of the platelet level in the blood. That's not a good thing because that can cause internal bleeding and so on. That requires transfusions. You know, nobody wants to see that.
We knew that we needed to reduce the dose. What we did after March was we started dosing patients using 50 milligrams. That was the lower dose, but also utilizing an intermittent dosing schedule, five days on, two days off, to try to obviously reduce the Cmax, if you will, of the exposure. What we saw there, and this goes back to a November 2024 press release, was that we reported data on eight patients that received 50 milligrams, five days on, two days off. On one hand, we were able to control for the thrombocytopenia. There was no grade 3, grade 4 thrombocytopenia. In fact, of the eight patients that were treated, one patient had grade 2 thrombocytopenia, which is really nothing alarming. That was great. We were able to control for that.
At the same time, that came at the expense of activity. We did not see any partial responses. We saw several stable diseases, including some significant tumor shrinkages, but nothing that mounted to the 30% reduction that you need to qualify for a partial response. What we did after that was we increased the dose slightly. Now we are treating patients using 75 milligrams intermittent dosing. As you can see, we are trying to kind of strike the balance between safety and efficacy, realizing that the therapeutic window here, to be candid, is not very wide. We need to, you know, really, you know, find the sweet spot where we think the drug can have an effect. That is what we are doing right now. There will be an update from the program in about two months on the patient cohort that is receiving the 75 milligrams intermittent dosing.
Hopefully, we'll be able to have an update with, you know, visible activity and at the same time being able to control for thrombocytopenia. That's what's going on with NXP 800 right now. Next slide, please. Regarding cholangiocarcinoma, this is the program that's being run by the Mayo Clinic. Don't worry about all this data, but this is basically a summary of all the preclinical PDX models that were conducted by the Mayo Clinic, obviously leading up to the start of the study that they're running right now. This basically gave them the motivation to want to run this study. This data came back very, very successful. They did it in their own labs. Obviously, you know, that kind of put pen to paper. They wanted to run the investigator-initiated study in cholangiocarcinoma. That's happening as we speak.
Hopefully, we'll have an update from this program sometime in the second half. Again, it's entirely run by them. We don't have any control over it at the moment. Next slide, please. In terms of the patient populations, the addressable patient populations that we're talking about, this is not an all-inclusive list, but these are the key tumor types that one can pursue using our drug potentially. Of course, we're going to be focused on patients that have the ARID1A mutation. You can see the different columns here, the overall patient population by way of incidence, and the percentage of patients that have the ARID1A mutation.
You can see that ovarian, for example, is relatively small, not minute, but relatively small, but areas like endometrial, which is something that we could expand into if we see a positive signal in about two months in ovarian, that would be a natural extension of something that we would want to do, is 10 times the size of ovarian. That could be a pretty, you know, sizable patient population. You can see that obviously it varies from, you know, bigger indications to smaller indications. By and large, this is kind of the marketing slide for the compound. Next slide, please. With that, I'm going to switch gears and talk about NXP 900. Next slide, please. With NXP 900, we truly believe that we have a potential transformational drug in our hands. This is a drug that could have utility in a number of areas.
It's really kind of like a pipeline in a pill, so to speak. This is something that, you know, if it works, can have significant ramifications across a number of tumor types. Basically, first of all, this is a compound that we licensed from the University of Edinburgh in Scotland. This is a compound that shuts down the SRC kinase. We also mention YES1 interchangeably with SRC. YES1 is kind of the main culprit within the SRC family. Let me give you a little bit of a historical perspective on SRC inhibition. There are other drugs that inhibit SRC. In fact, there are two that are on the market. There's a drug called Dasatinib, another one called Bosutinib. They are approved for two indications, CML and AML and ALL. They collectively generate close to $3 billion in those areas.
Obviously, they provide a real bona fide benefit to these patients. Obviously, that kind of begs the question, okay, if there are two SRC inhibitors that are on the market, why bother? Who cares about trying to come up with a third one? Here's why. Back in the day, Dasatinib and Bosutinib were tested extensively for solid tumors also, which arguably are a much bigger economical prize if you're able to succeed in those areas. They actually showed some pretty nice hints of activity here and there, but they always came across major systemic side effects when they were treating patients in solid tumors, things like immunosuppression, cardiovascular risk, you know, arrhythmias, things of that nature. That really prevented them from getting approvals in solid tumors. Obviously, that begs another question, why?
How come they succeed in liquid tumors, but in solid tumors, they were unsuccessful? What is it about them that prevented them from getting approvals in solid tumors? They just could not overcome these safety issues. Next slide, please. We believe that this picture here really answers that question. If you look on the right, this is a kind of heat map for Dasatinib. And Bosutinib, you can pretty much overlay on top of that. Dasatinib is a very dirty, very promiscuous SRC inhibitor. It hits a whole bunch of other things. In the solid tumor setting, it was almost like too much of a good thing. They started to encounter these safety systemic side effects, and they just could not overcome them.
The rationale for developing NXP 900 back at the University of Edinburgh in the first place from the get-go was to try to come up with a much more selective, much cleaner SRC inhibitor. A picture's worth a thousand words. I think they were very successful in being able to achieve that. You can see that NXP 900 is, in fact, a very clean SRC inhibitor, really hitting only what's in the upper left corner of this Christmas tree, which is, you know, the SRC family. I think we can kind of check the box on the selectivity profile of NXP 900. That's kind of the first step in the right direction. Next slide, please. Another thing that we believe that NXP 900 can potentially bring to bear is the mechanism of action, the way it shuts down the SRC kinase.
In the middle here, you see a caricature, obviously, of a SRC kinase. It has two active domains. Down below is the catalytic domain. That is where the phosphate molecule is. That is where the game of signal transduction or the passing on of messages occurs. Up above, where you see the turquoise and the brown blots, that is called the scaffolding domain, kind of like the communication hub of the kinase. Ideally, you want to shut both of these down. If you go to the far right, you see what Dasatinib does. Dasatinib is able to interrupt the catalytic domain. It shuts it down. That is a very good start. However, the scaffolding domain still remains intact. This is still a partially active SRC kinase.
The easiest way to see this, besides, you know, the chemical testings and measures that you can do, is when you look at the three-dimensional crystallography picture of the binding of Dasatinib to the SRC kinase, you see that the SRC kinase remains upright. It's in an open conformation. It's still basically a partially active kinase. If you go to the far left, right behind me, you see what NXP 900 is able to do. NXP 900 is able to shut down both the catalytic and the scaffolding domains. When you look at the three-dimensional crystallography picture of the binding of NXP 900 to the SRC kinase, you see that the SRC kinase is basically collapsed. It's in a closed conformation. It's completely incapacitated. That's really what you want to be able to achieve, complete shutdown of the SRC kinase.
We believe that this is what's happening with NXP 900. Again, a mechanistic advantage, we believe, over Dasatinib and Bosutinib, something that could play out very nicely in the clinic. Next slide, please. Right now, we're finishing up the phase 1A dose escalation. Obviously, as you all know, that's mandated by the FDA. You start at a low dose, and you go up and up and up until you find a dose that you feel comfortable taking into the subsequent trials. We started at a very low dose of 20 milligrams. We did 20, 40, 80, 150, 200, 250, and now we're at 300. We're going to stop here. Then we're going to start with the phase 1B, which I'm going to describe in some detail. So far, safety appears to be very clean.
Again, we're not seeing, you know, like the thrombocytopenia signal that we saw with NXP 800. We do believe that we're going to have a pretty wide therapeutic window with NXP 900, which obviously is very valuable, particularly if you want to dose combinations, which is something we intend to do. Next slide, please. This is kind of hot off the press. This is data that appeared at AACR. This is where we start seeing some real differentiation, we believe, between NXP 900 and the other SRC inhibitors. There are really three that are worth mentioning. There's Dasatinib and Bosutinib. There's an in-house SRC inhibitor that's developed, or the development for which has been, we believe, stopped by AstraZeneca for a drug called sarcatenib. That's kind of their in-house SRC inhibitor. They tried to develop a specific SRC inhibitor.
It was very specific, but it wasn't very potent. This is a very potent SRC inhibitor. What we're seeing here is the following. We measured the inhibition of SRC. What you see here is that at 80 milligrams, again, this is in patients that are not even the target patients, but we did this as a pharmacodynamic test to see how much inhibition we can generate using our compound. What you see here is something pretty profound. Basically at 80 milligrams, and this is the first dose, one dose, okay? What you see is that at 80 milligrams, we're already getting 50% SRC inhibition. The highest sarcatenib ever reached was 50%. The highest Dasatinib and Bosutinib ever reached was about 60%. We already get there upon first dose with 80.
At 150, 200, and 250, it's, you know, all bets are off. We're already at, you know, 85-90% inhibition, so even more. We're pretty much saturating the inhibition. We're basically maxed out on the inhibition, which is really a good position to be in. We truly believe that we've got, you know, really by far a best-in-class SRC inhibitor that is much more potent than the other SRC inhibitors that are out there. One thing, just, you know, as a point of reference, AstraZeneca actually ran a study using sarcatenib, which again is not a very potent SRC inhibitor, in an all-comers adeno lung patient population. They tested 25 patients. They actually saw two partial responses and a number of stable diseases, including one with a 29% reduction. Almost, you know, meeting the threshold of 30%.
Clearly, there was activity there using a not very potent SRC inhibitor and an unenriched patient population. They did not enrich for the different mutations and so on that we're going to be looking for, which is on the next slide, please. For example, on the right side, you see what the types of patients that we want to enroll into the single-arm, the single-agent arm that we're going to have in the phase 1B. We're going to be looking for patients that have, for example, YES1 overexpression. Why? Because YES1 is the key member of the SRC family, and it's implicated in a number of tumor types, including lung squamous and lung adeno.
Obviously, we expect that there will be a fair amount of lung patients within this particular single agent arm and a couple of other mutations that we believe have a tremendous amount of crosstalk with the YES1 kinase. We're going to be enriching for patient populations for the patient population and bringing forth, we believe, a much more potent SRC inhibitor. We really like our odds. Next slide, please. You can see the number of patients that kind of fall into each one of these categories. We're not going to go through each, you know, piece of the pie here, but, you know, these are very sizable patient populations, particularly when we look at them in aggregate in terms of the potential.
This could truly be a game changer in terms of the, you know, being able to categorically treat patients that, you know, would fall into these, you know, different criteria that we're looking for, namely these mutations and YES1 overexpression and so on. Next slide, please. Another approach that we want to apply is the combination approach. Both of these are going to be in lung. On the right side, and again, do not worry about all the detail. It's a very busy slide. I'll describe what we're looking at here. About three years ago, there was a publication that came out in a very prestigious journal called Nature Communications. This was a publication that was not done by us. It was actually done by the AstraZeneca R&D group. AstraZeneca, obviously, is the number one EGFR player in the world with Tagrisso, Osimertinib.
It's going to do about $7 billion this year in EGFR mutated patients in lung. Basically what they did here was they took cell lines that became resistant to Tagrisso treatment because what happens with these patients is they may receive a very prolonged benefit of two, three, four years, but eventually, without exception, unfortunately, all of them become resistant to Tagrisso treatment. Obviously, that's when their prognosis goes south pretty significantly. Basically what they did here was they took Tagrisso resistant cell lines. They implanted, they took these cell lines and then they took Tagrisso in combination with a bunch of other drugs. They wanted to see which combination would win this, you know, this competition in essence. Lo and behold, our drug, NXP 900, referred to here as ECF 506. That's the name the University of Edinburgh had for the drug.
Won this dog and pony show, and they tested Dasatinib, sarcatenib, and a bunch of other compounds. Hands down, NXP 900 performed best. That was kind of a eureka moment for us, you know, should we be looking, should we be looking at this opportunity much more closely, which is what we started doing. We started running a lot more tests of our own, more in vivo studies, more in vitro studies, replicated this experiment, by the way, and so on and so forth. That is another arm that is going to be included in the phase 1B. This will be a combination with Tagrisso, again, patients that are starting to fail Tagrisso. That is when you want to try to capture those patients to try to reverse that resistance, okay?
Same analogy applies to the left side of the slide here, which is the combination that we want to do with the ALK inhibitors. The two main players there are Pfizer with Lorlatinib, Roche with Alectinib. And, you know, same story. The benefit that these patients can receive can be three, four, five years in some cases, but eventually all of these patients inevitably will become resistant to ALK treatment. That is when you want to try to catch them. For example, some of you may be familiar with a company called Nuvalent. Nuvalent has a third-generation ALK inhibitor, basically, you know, trying to provide a benefit to patients that have failed Alectinib and Lorlatinib. At the end of the day, we do not particularly care who is going to be the number one ALK player, the number two, number three.
We think that we can provide a benefit to any of these ALK inhibitors because they'd like nothing more, just like on the EGFR side, they'd like nothing more than to extend the tenure of stay, basically to extend the time that the patients can remain on their drug before they need to be switched over or before basically they become resistant. Obviously, their prognosis worsens significantly at that point. Next slide, please. This is a little bit of a marketing slide, but you're all familiar with some of these numbers. The valuations in lung, simply because of the addressable patient populations, which are so sizable, the valuations are very robust in some cases. We're all familiar with Summit, with Nuvalent, and with some of the acquisitions that have taken place in lung. This is just kind of a snapshot of a few examples. There are more.
Hopefully, within, you know, a year or so, we'll have data sets that will allow us to become members of this very esteemed group of companies that have shown clinical proof of concept in, you know, different areas within lung. You know, hopefully we can get there. With NXP 900, we truly believe that we have that potential. This truly can be a transformational type of a drug that you don't come across every day. Believe me, I've been doing this for a long time. You know, you see niche opportunities here and there. This is much more than that. Next slide, please. This is kind of a housekeeping slide. We finished the first quarter with just under $30 million of cash. With our burn rate, we think that we have cash going into the first quarter of 2027.
Almost two years of cash from where we are now. That's not a bad position to be in for a small company, certainly in this kind of market. Another thing that's very important to mention is the insider ownership. When you look at the three co-founders and on top of that, the greater than 5% shareholders, there are three or four of those, or, you know, maybe just under 4%, but I'm kind of including them in the same group. Collectively, that's about 50%, maybe even 55% ownership. These folks have been extremely loyal. If you look at the form fours that are out there, including mine, by the way, since going public in February of 2023, there have been at least 25 or 30 form fours open market purchases, including some last week.
In terms of the milestones, as I described before, the balance of 2025 going into the beginning of 2026 could be very eventful for the company, perhaps even transformational with some key inflection points that we expect. With respect to 900, the phase 1A data, most of it is already out there, but the completion of that study is going to occur very soon with the completion of the 300 mg dose group. We are going to flip the switch into the phase 1B very soon. In about a month and a half or two, we're going to be starting the phase 1B. With respect to NXP 800, we'll have that update in about two months. If we see a clear sign of activity, we're going to move forward very aggressively in ovarian and possibly some other areas.
I'm going to stop here in the interest of time. I apologize. Thank you very much.
Thank you. Okay, very informative. Thank you, Ron. Yep. We do not have any time for any questions, but if you have any questions throughout the day, please reach out to Ron. Thank you. Thank you very much.