Everyone, welcome to our Annual Global Investment Conference. My name is Li Chen. I'm an equity research associate with Douglas Howe The next presenting company we have is Immunome. With us today is Mr. Clay Siegall, President and CEO of Immunome, a clinical stage biotech company developing novel therapies, including gamma secretase inhibitor and ADCs for cancer treatment. Please go ahead.
Thank you very much for the opportunity to speak here today. So I am very excited to tell you about all of the great work being done at Immunome. We are a company that's focused on targeted therapy for oncology. Before I get going, I'd like to say that I will be making forward-looking statements. Please refer to our SEC filings for more information. So the goal of Immunome is to really focus on establishing a premier oncology company and make great medicines that can help patients. For this year, we have a lot of anticipated goals. The first is to present our data, unblind our data on varegacestat. This is a once-a-day gamma secretase inhibitor, and it's for the treatment of desmoid tumors. And we'll get into a little bit of the information on the forthcoming slides.
The top-line data, the guidance, is for the second half of this year, which we are in now. I'm also going to be referring to the first of what will be many ADCs. This one targets ROR1 with our molecule called 1021. And it is important because not only is that an important molecule, but it utilizes our best and very advanced ADC technology that we're going to use not only with our ROR1 ADC, but with our next six ADCs all to solid tumors. Next, I'll be briefly mentioning our radiotherapy molecule targeted to FAP, fibroblast activation protein. It's a target I've been interested in for a long time because it's on 75% of solid tumors, but it's on the stroma, not on the tumor cell itself, making it very difficult to consider an ADC, but not a radiotherapy. That would be a great use of FAP targeting.
I'll briefly mention some of our novel ADCs and how it's going. We expect that we'll have three ADCs filed as INDs in 2026 of our next six, but we're moving really fast on all of these. The leadership team at Immunome is some fantastic colleagues that I'm proud to work with. A lot of them worked with me for a long time at Seagen, so I'm very happy to have them, but I'm excited to have others as well. Long-term, the goal of the company is really to make great drugs for cancer patients. It's what I've always done in my career. I have quite a few drugs that are on the market around the world that help cancer patients every day, and what I'm most excited about and passionate about is making cancer drugs, and that's what we are doing, making more cancer drugs for patients.
We do this through robust internal discovery efforts, but we also complement it with a strong and very disciplined business development. Okay. So the management team that I get to work with are a lot of talent. You could see that there are three Seagen folks from clinical, commercial, and tech ops that are in here. But we also have other executives that have really added a tremendous amount of value to the team. And we're really excited to do things good to help cancer patients. So the pipeline, I mentioned some of these, and I'll go through some of these. And I'll start with our phase III molecule, AL102. Like I say, it's a once-daily gamma secretase inhibitor. Now, there is a substantial patient population of desmoid tumors. And this is a type of cancer that is very painful, debilitating, and aggressive.
It doesn't kill patients like pancreatic cancer does. It's not a rapid death, but it is not a disease for the faint of heart. It is not something I would want any of you to have. It's very painful. It's a soft tissue disease. The incidence is high in young adults, especially women, are at greater risk than men, so it's something that we are looking at closely, and then in 2023, late in the year, there was the first approved systemic therapy, and that was nirogacestat from SpringWorks, now part of Merck KGaA, and so to me, they did a very good job of bringing in a molecule that was originally developed for neurologic disease with what I don't think are the right pharmacokinetic profiles and potency and whatever, but they did some fantastic work and got the very first drug approved for desmoid cancer.
The goal for us with AL102 is basically just to do a lot better for patients and bring forward a much better drug than the first drug that was brought forward. Gamma secretase inhibitors block the Notch pathway, and that's really a driver contributor to the growth of desmoid tumors, and so we think this is the appropriate pathway to target for desmoid tumors. AL102 is once a day. The first drug approved, Ogsiveo, is twice-a-day treatment, just as an example. We've talked to a lot of doctors on that. Doctors are very interested in the once-a-day, more interested in it than we first imagined because of patient compliance. It's not just making it easier once a day, but with more patient compliance to once a day, you can get better outcomes, so it's an important thing that we have come to appreciate.
So varegacestat was tested in phase II, and phase III is ongoing. We haven't unblinded it yet. But in phase II, we showed that at any of the doses we looked at, doses and schedules, that it was better comparatively than nirogacestat, which is the product that Merck KGaA owns now. So we saw in RINGSIDE part A, part B is our phase III study that we haven't unblinded yet. But RINGSIDE A, we showed deep and durable responses and were incredibly excited about it. It's 250 times more potent, and it has other pharmacokinetic differences varegacestat does than nirogacestat. We saw that the overall response rate in the best of the cohorts was 64% compared to a 41% with nirogacestat. And we saw that the tumor volume reductions were much deeper and stronger. We saw the T2 imaging, which reports on cellularity, is much better.
So in every parameter with varegacestat, we saw better data than nirogacestat. And so that's the reason why we embarked on performing and following up and do the phase III, doing all the CMC work and getting ready for potential commercial launch is because of what we saw in phase II and what we're excited to unblind in phase III. There are a number of different aspects of this. I talked about looking at RECIST, and this is done by a blinded independent group that's reading the scans. So we're doing it with the tried-and-true method of using BICR. We measure volume. We measure T2 or cellularity so you could see if it's active tumor. And we're doing all the measurements correctly, and we're really excited with everything we're doing. The safety in the phase II portion was very consistent with nirogacestat.
I wouldn't pull out anything in this small number in phase II and say that it's so obvious better or worse safety. I would say based on phase II, it's similar. We'll see what our phase III data gives, but I wouldn't read too much into safety differentials. And RINGSIDE phase III is our study that has not been unblinded yet. It's a randomized double-blind placebo-controlled study with once-a-day varegacestat versus placebo. There is a crossover to an open-label extension if you progressed with disease, which presumably would be placebo. So that is something that was allowed in the trial, which is very fair and moral to allow patients on placebo to get real drug. And the inclusion criteria is basically relapsed, refractory, treated patients that need treatment for desmoid cancer with ages of greater than 12 and real measurable lesions by MRI or CT scan.
The endpoints include PFS, which is a regulatory endpoint, but the very important endpoints of how doctors look at this often is with overall objective response rate, ORR, and duration of response, and that's done by a third-party review, which is the gold standard by FDA, as you know, and then there's a number of other endpoints that we're looking at as well: tumor volume reduction and PK and duration of response, et cetera, so we're very excited with our phase III RINGSIDE trial, and let me go back here, and we are expecting data this half year, so stay tuned.
When you do event-driven studies like this, you either unblind when you hit the event, and then all the sites turn in their data and you clean the data and you present the data, or you unblind when you don't hit the events and you're far from hitting the events and you speak with regulators, and regulators allow you to go forward at sponsor's risk, which is best-case scenario to hear from regulators. I've done event-driven studies in my career. The one before this was for tucatinib, which is now called Tukysa. We did not hit the number of events. It was slowing down to almost nothing. We went to regulators. They said, "Go ahead. You can unblind at your own risk." We unblinded. The data was phenomenal. This is at Seagen. The FDA approved the drug very rapidly.
So it's available around the globe for women with breast cancer that especially have brain metastasis where it worked very well. So that was tucatinib, now Tukysa. But it was just an example of where we did not hit our event number. I am not saying here we are or we're not hitting the event number. We're just providing guidance and saying we're doing the right thing by the drug. So I'd like to move forward now and go to our first ADC that targets ROR1. It's called IM1021. Now, ROR1 is an attractive target for an ADC because it does bind to both liquid and solid tumors, although it is at higher expression and more density on liquid tumors than solid tumors.
So if you want to make an ADC for solid tumors with ROR1, you really need to use an exceptionally internalizing antibody that internalizes fast and a potent selective payload. And so you want to use a great molecule, which is what we have developed. Now, I have been interested in ROR1 for some time. When I was running Seagen, I looked very closely at a company called VelosBio. And VelosBio had taken a ROR1 antibody that they had purchased from a small biotech that doesn't even exist anymore. They purchased that antibody, and it wasn't a selected antibody. It wasn't selected for high internalization or anything that I am aware of. They took that antibody and they connected it with vcMMAE, which I know well because I constructed that at Seagen. And that's part of Padcev, et cetera, and other things. That's the drug linker.
So Velos put it together, showed on some liquid tumors that there was some activity in dose escalation. Not much more than that. I made a short attempt to try to acquire the company, and then Merck bought them for about four times what I was thinking I was going to pay for it. So Merck put this drug into a lot of solid tumor trials since ROR1 is expressed both in solid and liquid tumors. And solid tumors are bigger market opportunities. And they did a lot of studies in combination with their phenomenal drug Keytruda. And they did not see anything that was noteworthy, and they closed down their solid tumor trials. In liquid tumors, they saw that there was activity.
Now, as a single agent, as they dose escalated, they found activity that was getting a little bit higher and more meaningful, but at doses that had too much hematologic toxicity. So they had to go down in their dose and then went ahead and did some combinations with R-CHP, dropping Oncovin, but using a lower dose of 1.75 mg per kg, not at 2.5, where it was a little bit too much, too toxic with a lot of grade three and four adverse events. So that randomized study that they're doing is underway. It's a long study. And good luck to Merck and to the doctors and patients on that trial. I wish them success. What my goal was in this and what Immunome's goal is to make a better drug, just plain and simple. And so that starts out with an antibody that was designed for rapid internalization.
That we have. We also have a proprietary payload, which I don't know of a better ADC payload out there. Most ADCs right now being developed are targeting the same 10 targets. It's kind of, to me, doesn't make sense. It's not the right way to go. What you'll see from us is all of our targets are targeting something that is unusual and different and rare. So we're excited with that. Now, our HC-74 payload is a Topo I. It does support a DAR 4 or 8 in our trial. So we can make it more potent if we want to. We see enhanced bystander effect, and that's because it's more permeable than a DXD type molecule. It has a very favorable therapeutic index, and it avoids standard pathways like P-glycoprotein, which prevent drugs and pump out drug and prevent drugs. These are resistance pathways.
So we have a Topo I drug that is not susceptible to resistance pathways, that has enhanced permeability and bystander activity, that clears fast if it ever falls off, faster than DXD if it falls off of the antibody, which all ADCs do with time. And it's also more potent than DXD. So we think HC-74 solves some of the problems that have inhibited DXD from treating certain patients. And so we're really excited with this. We started phase 1 trial. It completed our third dose level that we announced in a press release with our quarter in August. So we're continuing to develop this and continuing to do dose levels. We started at a substantive dose of 2 mg per kg because we had a lot of flexibility due to the safety profile of this drug. So I'm happy. Some ADCs, regulators make you start really, really low doses.
We did not have to do that because we had a very nice therapeutic window. And this is being done in both B-cell lymphomas and in solid tumors. Clearly, B-cell lymphomas would be lower hanging fruit since they have already been shown with ROR1 to be able to be targeted with activity. But nobody has a really good single agent, ROR1 ADC, that I am aware of yet. There's a couple that are being looked at. I think ours has a great chance to be the best and go forward very quick. So that's where we are with our ROR1 ADC. Now, I mentioned our payload just because Topo I inhibitors and antimitotics are really the workhorses of ADCs. At Seagen, I pioneered the use of antimitotics. Topo Is were drugs that certainly Seagen defined and explained but have been used by a number of companies.
What I really like is that we can use up to a DAR of 8. DAR is drug-antibody ratio. We can use 4, 8 without getting aggregation with clean manufacturing and all that. That's really important to go forward in making a drug that can work really well with ADCs. Our preclinical data in lymphoma and solid tumors is fantastic. Without spending a lot of time on it, we presented this before. It's really fantastic, and it's substantially better than the VelosBio, now Merck drug that targets this called ZV. Our clinical development plan goes through different dose cohorts and escalates up in B-cell lymphomas, including diseases like mantle cell, follicular, diffuse large B, and in a variety of solid tumors as well. We're very excited about it. That's part A.
Part B would be to expand in different cohorts in certain disease types where we see some signal in part A. So far, I am exceptionally excited about this drug. I really feel that it could do something. It could do two things. One is it could show that we have a really important drug here to develop. And the second one is it could read on our newest ADC technology that really solves a lot of problems that have been seen in the field. Now, I'd like to briefly talk about our discovery efforts in ADC. We have a lot of expertise in ADCs, and we have a great research capability.
And so we are looking at some of the most important and best targets and trying to understand what targets to use, why we're using a target, and not just repeating and copying what everyone else uses in targets. So we have been very active in that front. And I think that in the future, you will hear about some of our targets and be impressed by them. We are not releasing target names of all our next-generation targets yet because of the amazing work being done overseas that will duplicate targets and do the work. And so it is out of respect that we're not releasing all our target names yet. What we do is times have changed in that. Ten years ago, I would come to a conference and put up my 10 most exciting targets and put it right up here on the screen.
Now I can't do that. It's not appropriate. So now what we do is we set up very strong intellectual property, and we try to do as much as we can. We do composition of matter, combinations, manufacturing, how we conjugate, what we conjugate to, you name it, tumor types. And you try to establish a picket fence, a legal picket fence. And then you don't release your target until you really have to when you're in clinical trials. And by doing that, it gives you a huge head start, and it makes it more problematic for other people to try to copy what you're doing. So we're doing it the best way that we can in 2025 and beyond to protect ourselves. And so I'm very proud of what we're doing, and we have a clear strategy, and we have some phenomenal execution on our programs.
These 10 targets here, starting with HER2 and TROP2, represent more than 55% of ADCs in clinical development. To me, this doesn't make sense. And it just doesn't make sense. Some of these drugs that are out there for these targets are fantastic. And to do and make a new drug that's better is possible. But you will probably need four to five years, six, seven, eight hundred patients to try to show and prove that you're better than some of these existing drugs. And for a small biotech company, it's problematic. I just don't think it makes sense at all. And if a large pharma wants to do that, more power to them. With our strategy, we're prioritizing targets that have great biology and no approved ADCs.
And we're using our proprietary HC-74 topo inhibitor payload, which has all of the design features that you would want in an ADC. I talked a lot about HC-74 already and its low permeability and the potential, the efflux potential, and to avoid resistance. Our linker antibody synthetic molecule is phenomenal. We have not talked about our linker drug much yet, keeping it for intellectual property protection. And so, but we feel that we've looked at literally every drug linker out there. And instead of just grabbing a drug linker that exists, which most people do, we have a proprietary one that addresses some of the limitations in ADCs. And I think that's important when you think about going to the next generation of ADCs and not just repeating what was done a long time ago.
And we really think that this, when we compare it to DXD, which is one of the standards of care, workhorse, and ADC development, we have much better data across every aspect that we've looked at, whether it be cytotoxicity or permeability or efflux mechanism. So we're very excited and looking at that. And our data suggests that efflux mechanism resistance pathways are important. And if you take HER2 and you put it in patients that have P-glycoprotein type of a resistance pathway that pumps out the drug, you have lower efficacy than if you have breast cancer patients that have no P-glycoprotein. So we know in humans using DXD ADCs that there's an issue that we wanted to address. And so we have addressed that very much. And we overcome DXD resistance. And we've tested that in every model you can look at.
We have quite a number of novel development candidates, and so I don't think I have time to go through our novel candidates. I'll just go to the end. On our website, we'll have slides, and I don't have time to talk about our radioligand, which is very high science, and I'm really excited about going to clinic. We now have clearance from the FDA to start clinical trials with this exciting program, and so you can refer to our website for more information, but the last slide basically is just we're building a foundation for a transformative ADC company, but also a targeted therapy company to help cancer patients.
Thank you for the presentation. I think the floor is open to questions. Maybe I can ask one.