Yeah it's live. Okay. All right, good afternoon everyone. Welcome to TD Cowen's 45th Annual Healthcare Conference. My name is Tyler Van Buren, Senior Biotech Analyst here at TD Cowen. For our first session today after lunch, we have a hybrid presentation and Q&A with Immunome. It's my pleasure to introduce Clay Siegall, President and CEO of Immunome. Clay, delighted to have you here. Thank you for joining me.
Thanks Tyler and thanks to Cowen for inviting Immunome. Before I get started, I'd like to mention that I will be making forward-looking comments. Please refer to our SEC filings for more information. The purpose of Immunome is to really make fantastic anti-cancer drugs for patients in need. To do that, we have embarked on quite a few different programs, and we expect a lot of catalysts from many programs in 2025 and beyond. We have a phase III program varegacestat, which is a once-a-day oral gamma-secretase inhibitor for the treatment of a bone cancer, sarcoma type called a desmoid tumor. Top line is expected in the second half of the year. I'll talk briefly about that in my slides. We have another drug, an ADC targeted to ROR1 called IM-1021. The phase I initiation in patients is literally any day now.
We filed the IND in November. We were approved by FDA in December, so we are going to start trials very soon. We have another drug to file an IND this quarter, and it is a fibroblast activating protein FAP radiotherapy. The IND is on track for this quarter. Beyond that, we have a plethora of ADCs. We probably have more than a dozen ADCs we are developing. We are largely an ADC company, as we are going to be in the future, and we have great technology and great novel targets. Our cash runway is expected through 2026, probably into 2027. We recently raised capital and have a good cash position. Long term, we are really looking for two or more INDs per year, largely ADCs, and we are very well positioned to do corporate partnering as well.
The pipeline, which I just mentioned, starts out with our phase III product varegacestat and goes into 1021, which we are going to be treating patients very, very shortly, and our FAP RLT. Beyond that, we have a number of ADCs. I'll show you a little bit of data on some of those, and then more after that. I'll start with varegacestat . There is a substantial unmet need in desmoid tumors. Somewhere between 5,500 and 7,500 of these patients are actively managed in the U.S. each year. It is a soft tissue tumor, and it can be debilitating. While it is not fatal like a pancreatic cancer would be or something, it is a very painful, difficult disease to manage. V aregacestat is a gamma-secretase inhibitor, and it blocks the Notch pathway, which is believed to be a driver mutation in the growth of desmoid tumors.
It's a once-a-day pill, and that's important. It's in a phase III RINGSIDE trial right now. In November 2023, for the first time ever, there was an approved drug called OGSIVEO, and that drug was approved to treat desmoid tumors. That's fantastic that there is now a drug to treat desmoid tumors that's really paving the path. There is plenty of growth available, and we really like our drug. We think it has the potential to be a standard of care. Now, when you compare varegacestat with nirogacestat, and I apologize for the names being similar, they're both oral. Va regacestat our drug is once a day. Nirogacestat is twice a day. The data from RINGSIDE part A, part B is the phase three study ongoing now. Part A is phase II. It really showed some very strong responses.
When you look at overall response rate, whether it be evaluable or intent to treat, varegacestat performed much better than nirogacestat. And numbers you could see on the slides, whether it's evaluable or intent to treat, 75% and 64% objective response rate versus 44% and 41% with nirogacestat. Now, if you did respond, patients had with varegacestat an 88% reduction in tumor volume, which is very important. If you responded with nirogacestat, it was a 59% reduction in tumor volume. These are really important characteristics of our drug. We do not have the phase III data. What we're comparing here is our phase II data to nirogacestat's phase III data. Sometime late this year, we're expecting to unblind and really have a more true comparison.
When you look at safety in the phase II portion of the ringside, or ringside A, if you will, it's very consistent with the gamma-secretase inhibitor class. It's hard to really say that one of them or the other one is more or less toxic. I think there's a little bit going both ways, but I'm not too sure that there's much of a difference in safety. I would say that the safety of our gamma-secretase inhibitor is consistent with that class of drug. Like I said in my last slide on varigastat, the ringside part B or the phase three part is evaluating safety and efficacy in patients that are progressing with desmoid tumors. The enrollment of the phase three trial was rapid. It was completed. Right now, it's an adventure of a study. We're just looking forward to unblinding based on the events.
I'd like now to switch to our ADC programs. I'll start with 1021, which is the ROR1 ADC. It's a target that's clinically active. When I was running CGen, I took a close look at Velos Bio. Velos Bio was a private company developing a ROR1 ADC with the drug linker that I made, VcMMAE. This was an antibody that they had purchased from Oncocyte. It's a one-off antibody. It wasn't selected in any way like I normally select antibodies. I was very interested in potentially doing a deal with them. Before I could do anything, Merck came in and acquired Velos Bio for $2.75 billion. Merck put this further into clinic. What Velos had shown is in some mantle cell lymphoma and a few other lymphoma, but more mantle cell lymphoma patients, that there were anti-tumor activity.
You could see over on the right side, there's anti-tumor activity listed on the chart here. Unfortunately, a lot of it was done at a dose like 2.5 mg per kg, which is really too toxic to use generally in a patient as a single agent. You could see that this was an active drug. Now, why am I interested in ROR1? What am I looking at? The antibody we have now is much better. It internalizes rapidly. It's a much better ADC. It uses a different type of payload and linker. It's a TOPO1, which is an optimized TOPO1. The preclinical anti-tumor activity is just much superior to the MK-2140 that it's now called, the product that was originally made by Velos. Merck took this drug and put it into solid tumors.
What's unique about ROR1 is it binds to both liquid and solid tumors. Most antibodies bind to either liquid or solid, but ROR1 binds to both. It binds to solid tumors with a much lower density. You need an antibody that internalizes rapidly and really good potency to treat something that has low-density receptor. In liquid tumors, it's a higher density, so more readily treatable. In fact, that's what Merck saw. They saw some difficulty in solid tumors to treat, but it looked like it worked better in combination. They did a frontline study of 15 patients, showing that all 15 patients had a response. That's when you combine it with R-CHOP, which is very active in that type of lymphoma. They are going on doing a very long, I think it's like a seven-year phase III study, but discontinued for solid tumors.
The goal would be to have a much better ROR1 ADC. We looked at this closely. We showed that it has superior activity in the different models we looked at. We use a different payload completely. We call it HC-74. It is a TOPO1 inhibitor. It has a much better therapeutic index. It has a higher DAR, which is important when you are considering solid tumors. It has a strong bystander effect. You could potentially combine it with MME ADCs if you wanted to. The IND was cleared in December 2024, and we will announce shortly that we started treating patients with this drug. When you look at payloads, you want to have a very good high DAR to treat low-expressing receptors. That is what we have here. We use a DAR of eight.
We're really excited about the DAR of eight and using that. Microtubule inhibitors, often you can't use a high DAR. I think using a topo here to treat solid tumors especially would be very important. The solid tumor opportunity for 1021 is big. We have tested this in triple-negative breast cancer and non-small cell lung cancer, and we have tremendous anti-tumor activity, better than you would have seen with the Velos and now Merck product. We have a clinical plan, which is underway, with dose escalation in both liquid and solid tumors. As we see data, we will expand both in liquid and solid tumors and push forward there, and especially focus on single-agent activity. Now, I'd like to focus a little bit on ADC discovery strategy.
We have a great team, an experienced team that looks at targets rigorously and differentiated technology. We have a lot of experience and execute rapidly on ADCs. We advanced three novel candidates into development in 2024, and that does not include the ROR1 molecule. We have antibodies that are novel, or we are using antibodies that have previously been used, but we changed them around. I could think of a specific antibody where it was put into clinic as an ADC, but it did not internalize well. We, through engineering, made a rapidly internalizing antibody to this very interesting target. We are not aware that anyone is developing it now, but I would call it a repaired antibody. We use some of our antibodies that are novel and never been used before. Some are very exciting antibodies to things that have been tested before.
If you look at my time at CGen, we used antibodies such as to NECTIN-4, which was novel at the time. Now there's over 20 ADCs in development for it. We also used antibodies targeted to tissue factor, which now is a product, Tivdak. That was an antibody that a lot of people have looked at, but it was a better antibody than before. Now that's a product. I think both looking at novel antibodies and improved antibodies that have been used in the past are exciting ways to generate new targets. If you look across ADC now there's I think 100 companies or so. Maybe that's an understatement working on ADCs. Ten targets account for 55% of what's going on in the ADC world. I don't think this is appropriate.
I think this is too much duplication, too much wasted effort. We are focused all on novel targets that really we are going to be leading in there and be first in class, best in class. I also want to talk about our proprietary TOPO1 inhibitor, HC-74. It has properties that are better than DXD in preclinical models. We now need to show that in clinical models. It is superior potency than DXD. There are chemo-resistant cell lines where DXD does not work. We have a drug that works in those chemo-resistant cell lines. It has more permeability than DXD, so you can imagine it has superior bystander effect because you need that permeability. It also clears faster. All ADCs have a release of the drug. No ADC holds the drug on permanently. If it does release, you want it to clear rapidly.
We have increased clearance versus DXD. We really like this. We think this is a step above DXD. This does not count, and we are not discussing the linker, which we also think is superior. I would like to very briefly talk about a few novel ADCs. We are going to give them numbers here for the purpose of that. There is a lot of work going on internationally where they look for novel targets, and they try to just duplicate it. The work is outstanding, done by great scientists. This is a sign of respect for us to not talk about some other targets. We will mention the targets as we get closer to clinical trials, but we are filing lots of IP in a picket fence, covering everything that we could think and getting closer to clinical trials.
We will release targets as we see that it is more appropriate to protect ourselves. This is one target, which is in multi-indication solid tumors. We could go after colorectal, ovarian, breast, lung, and others. We call it IM-1617. We do not think anyone has ever tested this as an ADC. It would be the first one ever tested for this target. Our preclinical activity is extraordinary. We have tested it at 2.5 and five mg per kg in different models of solid tumors with outstanding anti-tumor activity, albeit preclinical models. We have also tested it in tolerability with non-human primates and can get up to 40 mg per kg. You can see we have a robust therapeutic window. I have developed many ADCs, and seeing a big therapeutic window is critically important. We have another ADC, also against a solid tumor.
This one could be a variety of carcinomas and neuroendocrine tumors and has very interesting biology. It is called IM-1340. That one, we also have very strong anti-tumor activity. In this case, we have strong activity as low as one mg per kg , which is very low. We have safety up to 40 mg per kg in non-human primates, so a very large therapeutic window. The third of these three have entered into development for INDs as soon as we can. We are working hard at them. Another one is a known target, but we understand the biology and have fixed what we need to for this antibody. We now believe that it is the only one that is being developed for this target with different engineering and technology that we are working on.
This one also is very active at 2.5 mg per kg and five mg per kg. We have three molecules in addition to our phase three, our phase III gamma secretase, our phase I ROR1, and the very soon to be filed as IND radioligand to FAP. We have three ADCs right behind that are moving forward fast toward INDs. For a small company, a big pipeline. This slide just shows three different ADCs. They're all identified with numbers. I'm not going to go through them all except to say that they all have extraordinary anti-tumor activity. You look at our pipeline, we have more than 50 novel antibody antigen pairs we're working on. We've interrogated pretty deeply about a dozen of them. We're really excited with what we're looking at. Most of them are in solid tumors.
I think that you're going to hear about our ADCs for many years to come. The last program I want to mention very briefly is our FAP targeted radioligand. I have been excited about FAP for a long time. It's expressed on 75% of solid tumors. The problem is that it's on stroma. It doesn't bind and internalize normally. I cannot make an effective ADC to it. Bringing a radioligand to this extraordinary target is possible. When you look at the history of this, Novartis brought a radioligand to it many years ago, and that program did not succeed. We know the molecule they made, and we understand why it didn't succeed. Clovis made a molecule that had some activity. There was a couple of responses.
We know that molecule too, and we know why we think why it did not succeed. This is a great target. Novartis bought the Clovis molecule and is in clinic with it again. They must like it. I have not seen any data lately on it, but we'll see. We made a molecule, and we looked extensively and did real science on it. We looked at a number of FAP ligands. There are probably 15 FAP ligands. I do not know that anyone's looked at them as extensively as us. We also looked very closely at the linker, and we made optimized linker. We also looked closely at the albumin binder status. Now, in Pluvicto, which is on the market to treat prostate cancer patients, they use a small albumin binder. What albumin binders do is it increases tissue residence time.
What we did is we looked at six different albumin binders that changed the time in residence of tissues to try to pick what's the best one. By looking at the best FAP ligand, the best linker, the best albumin binder, and the standard chelator, we could come up with the best science. To me, doing the best science is the way you come up with the best drug. I think that this target is extraordinary. If anybody makes a drug targeted to FAP, it's going to be a very important large drug because it's 75% of solid tumors. We're excited with our data. We're filing an IND this quarter. This just shows you some of the activity of the molecule. We used a beta emitter, which was important in this case. Alpha emitters are more potent.
When you're targeting stroma, you want the wider path length. Using a beta emitter with a wide, like a 10-cell path length, is very important. We think it made a lot of sense for us here. Just in summary, we are building a foundation for an important transformational oncology and ADC company in large regard. We do have a fully enrolled phase three with data coming out later this year. Two IND stage programs, one that's going to be already cleared as an IND and one to be filed soon. Three novel solid tumor targeted ADCs that we'll be filing INDs as soon as we can, working hard at scale-up and manufacturing and completing IND enabling talks. We have some differentiated technology to what we call reinvent ADCs and make them even better and a very large repertoire of antibodies.
I'll come over and answer questions from Tyler.
Wonderful Clay. Thank you very much for that presentation. I'm going to go ahead and start with your most advanced asset, varegacestat, since we have the phase three data coming in the second half of the year. Clearly, it's very potent, very selective, of great phase II data. Maybe you could just give a brief overview of what you believe the phase III RINGSIDE trial needs to show for it to be not only successful, but competitive in the marketplace.
When you look at the great work that SpringWorks did to bring the first drug ever for desmoid cancer as a proof for desmoid into clinic, they took a drug that was originally developed by Pfizer. It was a neurologic disease drug. It does not have high potency. They, through some very strong clinical development, got it approved. If you look at the FDA-approved trial, and I think that is going to be important to compare, the FDA-approved phase three trial with our phase three trial, which hopefully is FDA-approved someday. That is the apples-to-apples comparison. When you look at that, they had a 41% objective response rate with 59% tumor volume reduction in the patients that responded. They had a PFS score that was greater than a certain number of months.
I think when you look at what our data will be, what we unblinded, I think it's highly likely we'll also have a PFS that's greater than a number of months because these patients don't progress that rapidly. I don't think the PFS greater than a certain amount of time, it's hard to differentiate. What you have to do is look at what the doctors look at. We've interviewed a lot of doctors. We've talked to doctors. Almost every doctor on our trial was on the trial for the other disease because this is a close-knit group of doctors that treat bone cancers, especially like desmoid tumors. The doctors really know the drugs and know what to look for. They want to know what's the objective response rate. How well is it tolerated? In a patient that has a response, how deep is the response?
I think if you look at our phase II data, it's pretty extraordinary. You ask the question, what do we need? I don't know that there's a set thing. It's not like there's a light saying, here's the number you need. I know that they had a 41% objective response rate. If we come out of our phase three study and we have a 41% response rate, I'm going to be very disappointed. This is not why we're developing the drug. We're not developing it to be just like them, but once a day instead of twice a day, which some doctors say, hey, it's meaningful. It's not that meaningful. We want to get substantially better. We got in from an intent to treat, we were at 64% response rate at a valuable 75%.
We think we have a chance to be a lot higher in response rate. Also, we had 88% reduction in tumor volume in responding patients. They had 59%. Now, that's phase three versus phase two. What we need is phase three versus phase III. I think that we'll come up with the data. Clearly, varagacestat, our drug, is active. Clearly, it was active in phase II. We've talked to doctors. They're like, we like your drug, all that stuff. The doctors say a lot of things. I've done a lot of trials. I've done a lot of blinded trials. I've done event-driven studies. I've had a lot of drugs approved under my watch. I don't get too excited when I hear a doctor say, I love your drug. They say that a lot, but they don't have the collated data.
We just have to see what the collated data is and see if it's similar or a lot better, which we're hoping it is based on the phase II data.
OK, great. How large do you think the opportunity is in desmoid tumors?
There are over 30,000 patients that the prevalence pool in the U.S. So there's a big pool of patients. And if you had a really good drug that had a high response rate, you'd get more of them coming in. If it was a good drug and the higher your response rate, you get the better. And so I think that SpringWorks is doing a good job launching the drug. I've launched drugs like Adcetris in Hodgkin lymphoma. When you talk to the doctors, they say, we know how to treat Hodgkin lymphoma. We've done it for decades. And it took a while to kind of go in and pave the path with doctors. I think that what SpringWorks is doing is paving the path to saying to doctors, hey, there's a new mechanism here, an inhibiting Notch that you could treat. So it's really helpful to us.
By the time we come in, they'll already have heard it, seen it, and understand it. I think that's good. I don't know. We haven't come out with guidance yet on what the opportunity is. I've read some of the analyst reports on SpringWorks. I've heard various comments that this could be a billion-dollar opportunity. I think it also depends on how far you take it around the world. Our trial's in the U.S., in Europe, and in Asia. The intention would be to launch it around the globe. We have someone too. I hired a Head of Commercial who worked with me at CGen. He had two of the programs at CGen under him, two of the drugs. He went to Pfizer, and they promoted him and gave him more drugs. He now heads up our commercial. We're going to launch.
I think we could effectively launch very well in the U.S. and Europe. I think, like I did at CGen, I think for LATAM, as we call it, which is Mexico South, Spanish-speaking group, we used distributors very effectively. In the Middle East, we used distributors. In Asia, often you need partners because that's the way. They don't like using distributors as much as other territories. I think we could launch this around the globe and make this into a substantial product.
OK, great. We'll move to your favorite topic, ADCs, as you think about reinventing ADCs. Talked about the ToboEye novel payload with the data linker HC-74. I guess focusing on ROR1, the ROR1 ADC 1021 entering the clinic, when could we expect to see initial data approximately? What would you like to see with that initial data release?
ADCs are different than IO agents, for instance, or some other agents. With ADCs, you get data within the first three or four cohorts. You know if your drug works quickly. That's been my experience for 20 years developing these. You know if they work or you know if it's too toxic or other things or if they don't work. I am expecting that we get this information quickly. Our data safety package was good. The FDA allowed us to start at two mg per kg, which is a real dose. I'm very proud of that. I think that it is likely we'll have data to know how well this works by the end of the year.
Whether that's presented by the end of the year or not, it's hard to because you need to put things in for conferences five, six months ahead. The company will have data by the end of the year. I believe it'll be able to make decisions on moving forward. Maybe that's the first thing you see in how we're moving forward before it's even presented. That'll give you a little bit of insight into how well we like the program.
Good. I guess B-cell lymphomas, those sub-indications are fairly obvious based upon the history of ROR1. Solid tumors may be a little less obvious. How are you thinking about the opportunity in solid tumors for ROR1? Are there specific indications that you think are more exciting than the other? Are you going to start with a basket trial and go from there?
We'll start with a basket, but it'll be a few solid tumors that are the highest expressors. We're going to look at a basket, but it won't just be any solid tumor. I think that in liquid tumors, our ROR1, I would be surprised if it's not active. I would be surprised if it's not more active than the drug that was initially made by Velos Bio and now at Merck. They're not developing it as a single agent. They have this combination in front line that's a very long trial. I think the field is wide open for going fast, getting some data, transmitting that into an approval trial, and trying to get approval for the single agent in relapsed patients like mantle cell lymphoma, which is still pretty open. I mean, certain follicular lymphoma and others are better treated than mantle.
I think there is a big opportunity in mantle cell lymphoma. I think there is a chance for us to go very fast there. In solid tumors, our pre-clinical data showed it was much better than the Velos compound. I think we have a real opportunity. To me, if I was an investor looking at me, I would say, prove it to me.
Sure, Ok . The future ADC program, 1670, 1340, 1335, really exciting data that you disclosed earlier this year and we presented here. The beauty of ADCs is you're truly crushing tumors, right, as opposed to just slowing the growth or something like that with IO. Appreciate that you're not going to tell us that much more about the programs or the targets until they are getting into the clinic. Can you tell us anything about a rough timeline? Is it we're going to have to wait three plus years? Or is it a year or two away?
No. We're manufacturing now. I don't want to—we haven't yet set out the IND timeline. I would say all three of those will be in IND either late this year or in 2026. I don't think the INDs will be filed after 2026. It will be during that time and as early as possible. I'd love to get one this year and two next year or early next year or something. We're working hard at it. We're manufacturing as fast as we can. Our Head of Product Manufacturing, Phil Tsai, I worked with for 15 years at CGen. He manufactured and developed everything. He is a superstar. We were very, very fortunate to get him at Immunome. Not the whole company of Immunome is CGen people, but probably almost half. We handpicked the best of the best. We're going to make more drugs.
On the topic of more drugs, you mentioned that you have additional ADCs ongoing lead optimization. It's like three more or a handful more?
We have probably a dozen right now that are undergoing study in preclinical models. I think we're going to have two to three INDs per year every year as we look forward and possibly more. I mean, one of the things of having such a big pipeline of ADCs is it gives us the opportunity to potentially do partnering with some large companies. A lot of the large companies have spent billions, literally, in ADCs. Some of them have done well. I mean, you look at the ADCs that are out in the world. CGen-Pfizer, there's a bunch. Roche has two, Kadcyla and Polivy. I feel very connected with Polivy. I went to Roche many times, Genentech at the time, and sold them on the technology. It uses the technology I built. I trained them to do that.
That's now a product that passed the $ billion. There are nice royalties that Pfizer gets on it and deserve to. Roche has a couple. Daiichi clearly has Enhertu and a few more that it's making. Gilead has one that they've got through acquisition. There are not that many companies with these drugs. It's only a small number of companies that have the drugs. I look at our ADC technology that we have that we perfected. I looked at the sheer number of novel antibodies that look really good in ADC technology. I like what we have better than almost anybody. I think it gives us an opportunity to work with some of the big companies if they want to, but I don't feel pressured to do it.
That's great. We're out of time, so I'm going to wrap up. I wanted to end by asking you what you believe is the most underappreciated aspect of the Immunome story. Maybe it's your sheer number of antibodies that you're working on, but curious to hear you elaborate.
I would say the gamma secretase inhibitor could bring us to be a $3 billion company or something. The ADCs could bring us to be a $10 billion and beyond company. We think big.
Sounds good to me. Thank you very much, Clay.