Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, Biotech Analyst with Cantor. With us, we have Nuvectis, a company we recently initiated coverage on. I'm pleased to introduce Ron Bentsur. Welcome, and thank you for joining us.
Thank you very much.
Let's start off with a brief intro of yourself, followed by a snapshot of the company and how you think about the company today following that Haisco transaction.
First of all, thank you very much. Thank you for inviting us to the conference. It's a pleasure to be here. My name is Ron Bentsur. I'm the CEO and also Co-Founder of Nuvectis. Prior to Nuvectis, the management team was involved with three different companies, Keryx Biopharmaceuticals, Stemline Therapeutics, and UroGen Pharma. I was the CEO of both Keryx and UroGen, and a longstanding board member at Stemline. At each one of these companies, we were fortunate enough to get a drug approved. At Keryx, it was a drug called AURYXIA, which actually has two approvals. The first one as a hyperphosphatemia agent for dialysis patients, and the one that actually was very important to the transaction that we did with Haisco was as an anemia agent for pre-dialysis patients.
That is important because one of the assets that we brought in as part of the transaction, obviously, is anemia-related. At UroGen and Stemline, we got oncology drugs approved. I am sure some of you follow UroGen, and some of you recall Stemline, which was acquired by Menarini in 2020. That is the background, and we started Nuvectis in late 2021. We completed the transaction with Haisco about two months ago, two and a half months ago. Courtesy of Cantor, we did a follow-on offering right after that. We raised $150 million, and here we are.
All right. Could you just walk us on, as you just mentioned, the deal that you did with Haisco. Just walk us through the term details and how that transaction sort of came together.
The transaction with Haisco came together as a result of—it is basically a two-year relationship that started out with the oncology compound that we brought in also as part of the transaction. In fact, when it was still late pre-clinical. One of our people at Nuvectis took an interest in the compound and started the dialogue with Haisco about that compound, which we now call NXP200. It obviously went into clinical trials and showed some very good data and responses, and we became very interested from a business development perspective. That kind of went along, and during that process, they also introduced us to the second compound, which we call NXP100, which is the complement Factor B inhibitor. About a year ago or so, maybe a little bit more, we were introduced to that compound. We started dialogue around both of them.
It took time, and obviously the chemistry between the teams needed to be there, and they needed to feel confident enough in our ability to move this down the field. Again, we were fortunate enough to be able to bring in these two compounds. We are very happy with the transaction, and they are a terrific, in fact, an incredible partner, extremely smart, and truly an exceptional development team over there.
Many companies are being formed around or expanding the pipeline with China-originated assets. But some investors still apply a very large discount. What diligence did you conduct that got you comfortable around the other licensing of 100, and what can you share with investors?
Sure. We conducted obviously very extensive due diligence on all the aspects that you would expect. Pre-clinical, CMC, IP, of course, and of course, all the clinical data. I think it's also important to add that we closed our deal in June of this year, so about two months ago. Right before us, in fact, in the second quarter of 2026, Haisco closed two big pharma deals. The first one was with AbbVie, and about a month or a month and a half later, they closed a deal with Eli Lilly. As you can imagine, they went through the wringer in terms of due diligence, and they passed with flying colors. I think we're in a great position. We feel very comfortable with Haisco as a partner.
100 shares the same mechanism of Novartis' FABHALTA, which is approved in PNH, C3G, and IgAN. This obviously derisks the target, Factor B. We have an approved Factor B inhibitor. Why do we need another one? What I'm driving at is how is 100 differentiated from FABHALTA?
Yeah. FABHALTA is really the first and only Factor B on the market. It's an oral, and it's kind of slowly but surely overtaking the PNH space for two reasons. One, it's an oral versus SOLIRIS and ULTOMIRIS, which are injectables. But also the data for the Factor B is superior, and it's not even close actually. If you compare the data for the Factor B versus SOLIRIS and the C5s, there were two studies that were conducted. One was by Novartis with FABHALTA doing a head-to-head study against SOLIRIS. The second one was Haisco with our drug NXP100 doing a head-to-head study against SOLIRIS, and it's not even close. The Factor B are clearly superior to the C5s.
When you combine those two factors together, the fact that you are talking about an oral, which is much easier, and a much better drug, I do not think it is a question of if, it is really a question of just how fast the Factor B are going to overtake this multi-billion dollar market. The PNH market currently is about $5 billion, maybe $5.5 billion, soon to become $7 billion or $8 billion. That is the expectation by the end of the decade.
A multi-billion dollar market that is going to be overtaken by the Factor B, initially FABHALTA, of course, and then hopefully us. You talk about the differentiation. We are once a day, they are twice a day. Obviously, there is a huge convenience advantage there. Think about lifelong therapies. These are all lifelong therapies, and we are not talking about keeping patients compliant for the first week.
Obviously, everyone is going to be compliant for a week or several months. The question is what happens after years and years of treatment. You do not want to lose compliance, especially not in a disease like PNH, because that can lead to very adverse outcomes. Keep in mind that before any drugs were introduced into the PNH market, the life expectancy of patients from diagnosis was less than 15 years because unfortunately, many of them died due to thrombotic events. The fact that SOLIRIS and ULTOMIRIS made it onto the scene was a huge blessing for the patients. Now they live pretty much a normal lifespan, but they have to be controlled. If they start losing compliance, they can run into these events, and these events can become deadly. You have to make sure compliance is airtight.
The fact that we can show up there with a once a day versus a twice a day, again, talking about years and years of treatment, we think can be a pretty substantial advantage.
All right. Can you just walk us through your development strategy? You have disclosed you will start off with PNH, but how are you thinking about the overall strategy, approved indications versus indications that FABHALTA and NXP100 are being evaluated in, versus white space? How are you looking to maximize value for NXP100?
Sure. PNH obviously is center stage right now. Basically, where we are right now is that this compound is already approved. It has received the initial approval in China for PNH naive patients. That happened about a month and a half ago. Haisco is expecting to receive the second Chinese approval in PNH pretreated patients. That is expected by the end of the year. Obviously this is a late-stage compound. What we want to do here in the U.S. is have a conversation with the FDA. We are due to have that, what we call the pre-IND meeting. We need an IND to be able to conduct clinical trials. At the same time, we want to get a roadmap from the FDA, basically marching orders about what it is going to take to get the drug approved in the U.S.
Our expectation is that the FDA will probably require us to do some sort of a PK study in healthy volunteers, followed by one, maybe even two pivotal studies. We are gearing up for that. If it is one study, obviously that is pretty straightforward. If it is two studies, we will start those simultaneously. What that would probably mean is a study in naive patients and a study in pretreated patients similar to what went on in China. That is kind of the base case. We are gearing up for that. That is basically what we plan to do in PNH.
If you look at the expected timelines for something like that, we are going to have the, obviously, clarity from the FDA in the fourth quarter. We will be able to start those pivotal studies, let us say in the first half of 2027, have data by the end of 2028, be in a position to file an NDA in the first half of 2029, and hopefully have the drug on the market by the end of 2029, beginning of 2030.
Hopefully, shorten the time horizon with breakthrough designation or something like that. That is kind of the base case expectation. A couple of things I think are important to understand when you look at just the overall picture. When you look at the FABHALTA, if I may, Peter, when you look at the FABHALTA NDA or the pivotal data, 40% of their patients were Asian.
There are absolutely no differences in terms of safety and efficacy between the ethnic groups. In fact, when you look at the FDA summary overview, the interdisciplinary summary overview for the FABHALTA NDA, the FDA clearly states that PNH is not an ethnic sensitive disease. Okay? Now we have the Chinese data, a lot of it. It is a full data set. On top of that, our drug is an analog of FABHALTA. What Haisco did was they took the FABHALTA drug, the scaffold or the backbone, and they applied very clever optimization techniques to increase the PK and achieve better PD and things like that. Of course, that constitutes an NCE and also a very strong composition of matter patent, which was issued, in fact, actually about a month before we closed the transaction with Haisco.
But in any event, it is still an analog of FABHALTA. We kind of like our chances with respect to the dialogue that we are going to have with the FDA. We are going to find out in a month and a half, two months or something like that. That is basically the plan for PNH. I think there is a very big prize that awaits. I think the Factor B, initially, obviously FABHALTA is going to slowly but surely overtake that market. When you look at the ramp-up, in the second quarter FABHALTA had $225 million in revenue, almost all of it is PNH. This follows the first quarter number of $167 million. You are already seeing that ramp-up start to occur. They are already at a run rate of about $1 billion.
I do not think it would shock anybody if by the end of the decade, put us aside for a second, if by the end of the decade, FABHALTA will do $3 billion, $4 billion, $5 billion in PNH alone. Now to your question regarding some additional indications and where we think Factor B can go and where we can go maybe even more specifically. FABHALTA has three approvals, PNH, IgAN IgA Nephropathy, and C3G, which is a smaller nephrology indication. Right now, their main focus is on PNH. They have got a PNH price point, et cetera. They are also running six additional clinical trials and six other indications. Lupus, myasthenia gravis, dry AMD, things like that. Some of these are extremely lucrative indications. For example, myasthenia gravis, to show up as a first oral class could be huge.
I think that is something that Novartis is trying to capitalize on. We are keeping a very close eye on all these studies. Those cards are going to be flipped over the next three to nine months. Some will happen by the end of the year, some will happen into 2027, but we are talking about six new potential opportunities, some of which could be obviously very substantial. On the Haisco side, Haisco is running some studies of their own. They are running a phase II study in Lupus, which is expected to read out, I believe, by the end of the year. They also are about to start a dry AMD study, and I believe also a myasthenia gravis study in China. There are a lot of moving parts, a lot of potential indications.
When it is all said and done and the dust settles, I do not think it would surprise anybody that the Factor B could become north of a $10 billion class. There are really only two games in town. There is FABHALTA and there is us. We are going to basically be a fast follower with a once a day versus a twice a day. I really like our positioning, and I like our chances.
Right. I guess, any of the clinical data, exactly what did you like when you looked at Haisco's PNH data? They ran two studies, disclosed outcomes for both of those.
When you look at the Haisco data, it is very compelling. In PNH, what you try to do is increase hemoglobin in a robust fashion. These are patients that are extremely anemic. Their hemoglobin dropped to levels of 7, 8. They can barely get out of bed, and that is without these potentially deadly events that they can encounter, the thrombotic events and all that. It is very important to kind of boost up their hemoglobin. Haisco ran two studies.
Again, this was very similar to what FABHALTA did to get their approval. They ran a patient-naive study. These are newly diagnosed patients where they went head-to-head against SOLIRIS. Basically, what they showed there was a dramatic advantage over SOLIRIS. The primary endpoint was a responder analysis of the portion of the patients that achieved a hemoglobin above 12, so they are no longer anemic.
The result was 60% or something like that versus 8%. Clearly a huge difference between an efficacy in favor of NXP100. If you look at the average hemoglobin increase that was achieved in that study, it is even more staggering. For NXP100, it was a little over 5 points, which is pretty remarkable. For SOLIRIS, it was I think 2.2 or something like that. More than a doubling of the hemoglobin increase versus SOLIRIS. It does not take a genius to figure out that obviously it is clearly superior to SOLIRIS. In fact, when you look at the FABHALTA data in their head-to-head study against SOLIRIS, it was pretty similar. Then Haisco ran a pretreated patient study.
These are patients that basically were on a C5 and failed, and now their hemoglobin is going down and they are becoming severely anemic, and so on and so forth. Obviously what you want to try to do is kind of reboost their hemoglobin level. Similar type of an endpoint, the percentage of patients that went above 12, and they achieved that with flying colors. The average hemoglobin increase in that study was 4.6 or something like that. The data is overwhelmingly positive. It is very clear. Another thing that is encouraging, I think from our perspective is that when you look at the safety profile versus FABHALTA, they are almost identical. It is almost like identical twins. You can pretty much superimpose the safety profile of one on top of the other, very similar.
When you look at the efficacy, again, these are cross-trial comparisons, so obviously it is not exactly apples to apples, but our data at least optically looks a little bit better in terms of the average hemoglobin increase and all that as compared to FABHALTA. Again, when you look at the overall PNH package that has emerged from China, so two pivotal studies, phase IIIs, one phase II, I think five or six phase Is. A very extensive package, a lot of safety information, really everything that you want from a very well-designed, very well-orchestrated clinical plan, a clinical development plan executed by Haisco. That is the kind of information that we are going to show to the FDA, and the FDA is going to decide what we need to do in the U.S. to get the drug approved.
All right, so on that point, investors are wondering about the regulatory strategy and sort of path forward for PNH. You got it to a pre-IND second half of 2026. Any sort of granularity of when you expect to meet with the FDA and-
Yeah.
-the expected IND submission?
Yeah. We expect to meet with the FDA within the next month. We may not have final answers at first glance or first iteration. It may require another iteration. But we are highly confident that by the end of the year, we will have full clarity on what the FDA wants. Again, we are prepared internally. We are gearing up to conduct two studies if we have to. That is kind of the base case.
Again, treatment-naive, pre-treated patients. If we have to do that, we will start those simultaneously, and whatever study reaches the finish line first, that will be the NDA that we file first. If we get any discounts on that, great. But the base case is that we will need to conduct a PK study followed by two studies which we can start in the first half of 2027. We will have full clarity in the fourth quarter, I believe.
Okay. A PK study will also start in the first half of 2027.
A PK study in healthy volunteers can start relatively quickly. It is something that we may even be able to start by the end of the year.
All right. How are you thinking about phase III designs? Are you going to stick with the design FABHALTA used for approval or replicate your partner's designs? Because I think there are slight differences there. What are your thoughts there?
In terms of trial designs, it is interesting because the trials were very similar. If you look not just at Haisco and what FABHALTA did, but also when you look at the SOLIRIS and ULTOMIRIS studies, that is the Alexion AstraZeneca franchise. In terms of patient numbers and in terms of the endpoint, the endpoint is a 24-week endpoint for all of these studies, so that is probably what we are going to do. The patient numbers were almost identical. The number 35 patients per arm keeps on coming back.
When you look at the Haisco studies and all of these studies, each arm, whether it was the randomized study versus SOLIRIS or the single-arm study in the pre-treated patient population, it was 35, 36 patients, something like that per arm. When you look at the FABHALTA studies also, that number keeps on repeating itself.
And also in the SOLIRIS and ULTOMIRIS studies, it is interesting, but again, that number was pretty much identical. First of all, it is an ultra-orphan disease, so obviously you are not going to be able to find 500, 700 patients to conduct a study. But because these things move hemoglobin quickly, you do not need a million patients to prove your point. So you can apply all the power assumptions and all that with a relatively small N. So again, if I had to envision what the studies are going to look like, I think they will kind of look and smell very similar to what we have seen in the past.
Okay. So on your pipeline chart, it does say undisclosed, second undisclosed indication. How are you thinking about that?
So in terms of additional indications, so obviously we know where FABHALTA is already approved. So FABHALTA is already approved in PNH, IgAN, and C3G. One word on IgAN. So in IgAN, obviously, there are a lot of moving parts right now. The APRIL BAFFs are out there. They are very effective, and there are five or six of these being developed. And of course, two or three are looking a little bit better than the others, and they are probably going to be the front runners. But keep in mind a couple things.
One is they are injectables. We are an oral. And then when you look at the data that has been generated for us and also for FABHALTA, there are a couple of interesting take-home points. One is, as many of you are aware, in IgAN you need to show proteinuria reductions and you need to try to stabilize eGFR. And some of the APRIL BAFFs are certainly capable of doing that. When you look at the FABHALTA data, it is very effective, but it comes up just a little bit shy of being able to reduce proteinuria by, let us say, 50% or 55%, which is what the APRIL BAFFs are able to do, or the best ones, and stabilize eGFR.
Again, you are starting to split hairs here, but they are a little bit shy of that. Whereas when you look at the phase II data that was generated by Haisco, and by the way, right now they are running a pivotal phase III study, which is going to read out in the second quarter of 2027, which obviously will be very telling for us. But when you look at the phase II data that was generated, and it was not a small phase II, their data where they achieved about a 57% proteinuria reduction at week 24 and an eGFR increase of almost 3 points at week 24.
If that data is sustained in the phase III, I think NXP100 can become part of the conversation for, okay, what can be frontline therapy? Because it stacks up to the best APRIL BAFFs. Again, we are going to need to see it in the phase III, but there certainly is that potential. So when you compare that to FABHALTA, here is a situation where the better PK, the better PD could be translating into slightly better efficacy, but enough to take you above that threshold where now you can have a seat at the table and be part of that conversation for what could be frontline therapy for IgA nephropathy.
But let us put that on the side because we are waiting. We are not doing anything until we see the data that is going to emerge from the phase III study in China. Additional indications. So, Haisco has gotten approval in C3G. That is a very interesting indication, although it is pretty small. But there is a pediatric component there, which could be important with the vouchers and everything else. Of course, there are all these other studies that they are conducting, in areas such as myasthenia gravis, which is extremely lucrative. That is very high on our priority list.
We are going to wait for the data to emerge from the FABHALTA study, which hopefully will be in the first quarter of 2027. I can tell you that we do plan to gear up for a study. We are not going to start it until we see the data, because if the data is bad, we do not want to do the study. But if the data is good, we want to be ready to start the study very quickly thereafter. So that is definitely on the priority list for us. Again, unless things change for us over the next few months, that is probably something we are going to go towards. Then we are going to wait for them to flip the card on a couple of additional things. We do have some ideas for some white space areas as well.
These are areas that we do not believe Novartis is going to go into because they are too small or they may not be a good fit or something like that. But just to reassure everybody, we are a small company. We cannot do 50 clinical trials simultaneously. We cannot overextend. We need to be very careful. So PNH first, that is the number one priority. Then we need to see how much capital is left. So, myasthenia gravis is definitely up there. To the extent we have got some bandwidth and all that to run another study, again, we need to be very careful about how we prioritize it. So that is the way we are looking at these different opportunities. I think we are in a very fertile land here, where there could be a number of terrific opportunities for us to pursue.
There's nothing better for a small company to sit there and wait, and have a very smart big pharma doing all the heavy lifting, doing all the education, doing all these clinical trials to provide us, little Nuvectis, with a roadmap of where to go. Again, going back to what I said before, I think we're very well-positioned.
All right. You have roughly $130 million in cash runway guidance into first half 2029. Just walk us through what programs have been incorporated in that guidance, and how are you thinking about funding future pipeline expansion?
With the cash that we have right now, we do have enough to take us into the first half of 2029. More importantly, we think it's enough to complete two studies in PNH if we need to run two studies and another clinical trial. Beyond that, I'm not sure we have enough money to run a fourth study. But to run two studies in PNH along the lines of the magnitude that I described before, 35 patients in each arm, maybe one of them needs to be a randomized study with a six-month endpoint and all that. We do have enough capital for that and to run a phase II in, let's say, myasthenia gravis, assuming that's what we want to do, and right now it is a high priority for us. So yeah, that's where we are right now in terms of cash.
Then spend on NXP200 and NXP900?
The spend on the oncology compounds NXP200, NXP900. The legacy compound NXP900 is in a phase I-B that is relatively a small burn. We are doing some combination studies there with osimertinib, with TAGRISSO. There is another combo that started with lorlatinib. This is all in a non-small cell lung cancer. But again, these are relatively small phase I-Bs.
With NXP200, the second compound that we brought in from the Haisco deal, that is a second generation, the paradox breaker, BRAF inhibitor. That is a program that is going to start in the first quarter, but we are waiting for the phase I-B data from the ongoing phase I-B study that is being run by Haisco in China to inform that phase I-B study that we want to run in the U.S. Specifically, we know we are going to go into CNS. I think that is a given. The data there has been very strong.
But we want to see what kind of data Haisco is able to generate in their phase I-B in other tumor types, colorectal, melanoma, non-small cell lung cancer, papillary. These are the classic BRAF mutation types of tumors. I think that will help us basically design the phase I-B. But going back to the expenditure component of it, phase I-B is in the grand scheme of things, relatively speaking, they are not zero, but they are not that expensive. I think we certainly have enough money to run those as well.
All right. Last question. We are sitting here 12 months from now, and I ask you, what have been the key value-creating accomplishments for Nuvectis? What would you like to say?
In terms of the inflection point, I think there are going to be a lot of potential catalysts. All these flipping of cards on all these clinical trials that Novartis is running with FABHALTA, I think that is going to obviously provide hopefully positive ricochet effects for us. For example, if they generate positive data in lupus, dry AMD, gMG, of course, I think that is going to resonate positively for us. All those things are going to happen within the next three to nine months. I think FDA clarity is very important for people. They just want to know that there is a clear path, and it becomes purely an execution story. I think the clinical risk is very low.
Also, I think people are looking towards the second Chinese approval, which hopefully will occur by the end of the year to give that added level of confidence. Those are really the key milestones that I envision over the next, call it three to six months.
All right, Ron, thank you very much for participating-
Thank you so much, Peter.
-at the Cantor Healthcare Conference.
Pleasure to be here.
Yes.
Thank you very much.
I look forward to the progress.
Thank you so much. Thanks. Thank you.