Conference Transcript - IMNM 2026-09-14

Andres Maldonado, Analyst — H.C. Wainwright

I'd like to welcome everybody back to the H.C. Wainwright's 28th Annual Global Investment Conference. My name is Andres Maldonado. I'm a senior biotech analyst here at the firm, and it's my pleasure to welcome you. Continuing with our morning session, our next fireside is with Immunome, and it is my pleasure to welcome President and CEO Clay Segal. Clay, wonderful to see you as always. Thank you very much. Enjoy being here. So to start, for investors less familiar with the Immunome name, can you walk us through the pipeline and how you're prioritizing the portfolio today?

Clay Siegall, CEO

Sure. So the goal of Immunome is to make targeted therapies for cancer patients. I've made quite a few drugs that are on the market around the world in my career, and it's my passion to help cancer patients. You know, working with lawyers and accountants may be not so much of a passion, but making cancer therapies is. And so I really enjoy it. And what I decided with Immunome is to make a big pipeline and think big. And I know a lot about ADCs. I made a lot of ADCs on the market. And so what I wanted to do was make ADCs that solve some of the problems of ADCs historically that were made. And I could go through that in a moment. And so we've made, we have at least 10 ADCs, novel targets, the best ADC technology, in my opinion, out there in the world. And we're pumping them into the clinic one after another after another. But while doing that, I also wanted to build a company. So I looked at dozens of small molecule drugs when I ran CGEN for 25 years. I looked around at small molecule drugs, and I brought in Tucatinib, which became Tukiza in 72 countries approved, a great drug helping women with breast cancer. And so I went out and looked at loads of dozens of drugs, most of them from little companies that either were underfunded or didn't know how to develop it or whatever. And a lot of the drugs I looked at were not acceptable. But I found one like I did with Ducatinib when I was at CGen. I found varagastastat. And it was, we thought, based on the phase two data, the real deal. And when I look at gamma secretase inhibitors, I looked at it and the varagastastat had great pharmacokinetics. And that was really the difference between that and nyrogastastat, which is the only gamma secretase inhibitor on the market. And so that led us to look at all the data and everything and bring that in. And we did all the CMC. There was no CMC done. We invested in it, met all the doctors, got all the phase three done, and the data was fantastic. It's the best drug out there. And we submitted for approval. We have a PDUFIDATE. I'm very pleased with our ability that we're going to help patients around the globe. And we have good plans to launch it everywhere and get it to the patients in need. So it's very similar to the tucatinib story to bring in a drug with phase two data from a company that was underfunded, no CMC, problematic, but make it into a real drug while I'm working on ADCs. So we have tons of ADCs. We even have one radio ligand that we're developing, but mainly ADCs. So I'm really excited for our future and helping cancer patients.

Andres Maldonado, Analyst — H.C. Wainwright

Great. So before we touch on the ADC program, maybe a couple of quick follow-ups in Vargasistat. I guess, can you talk to us a little bit more about, given that desmoid tumors are a chronic treatment journey, you know, how are you thinking about, you know, the optimal duration of therapy so us as analysts can model it correctly?

Clay Siegall, CEO

So, you know, I have done as much study of desmoid cancer. It's a subtype of a sarcoma. It's treated at SARC centers. They call them SARC centers around the U.S. And internationally, they're sarcoma centers as well. These are interesting tumors. They don't kill patients. And it's like pancreatic cancer kills patients fast. This doesn't. This is just really painful, really difficult for a patient. You don't want your enemy to have this disease. It is not fun at all. And I've talked to a lot of doctors, a lot of patients about it. The pain is the biggest thing in dealing with it. You know, there's 1,650 new patients a year in the U.S., about the same when you look at the whole EU as a group. And there's 11,000 prevalence. And a lot of them are doing what's called watch and wait. And sometimes doctors will give them radiation. Sometimes they'll give them sutent. I mean, it's just barely doing anything. And then the first gamma secretase approved was niragasus, that from spring works now uh merck kga and so that was the first step and when we looked at this we talked to doctors and we you know we think about it in our phase three trial our average duration of treatment was 20 months okay that's something now i will tell you that i've had i've developed a lot of drugs that a lot of proof in real life it's always less okay every drug i like to lie to you and tell you it's going to be more or whatever but every drug i've ever made and And that's a lot of them are always a little less than what you'd see in a clinical trial. So I don't know what it's going to be. If I had to guess, I'm going to say 16 months, not 20, something like that. It's not like way less, but it's always a little less. Now, doctors ask us all the time. They go, Clay, can we retreat with this? Like, can we put someone on for a year and a half and then let them live their life? And then if we need it, come back. Well, I faced the same thing with Etcetris and Repetsev and all these others. And so I've done retreatment studies with other drugs. And if you get good data, you get a label. for it with FDA. So we listen to doctors, ask a lot of questions and we're doing a retreatment study. So I don't have that answer for you. I think it's going to work just fine. Okay. Based on circumstantial evidence, but I need to do the study and then try to get a label. And that's what the doctors want to know. Okay. And, and they want to know also, so how quick is the temporal, what's the temporal nature of pain relief? Cause that's what the biggest complaint is, the pain. And it goes along pain means tumor, you know, where you reduce the tumor, you reduce the pain. So it kind of goes hand in hand. And so that's something really important to hear. And we've talked to patients, like some of the patients, they go within two, three weeks, wow, we feel so much better. Our pain's way down. Within a few months, our tumors are like almost gone. Almost every patient, I don't remember the number, 95% some odd of patients have a pretty dramatic anti-tumor activity. So it's a very high number once a day. It's a group of pills once a day, but we have developed a single pill once a day that's going to come out, not at the approval, but shortly thereafter.

Andres Maldonado, Analyst — H.C. Wainwright

Great. And maybe a quick follow-up before we move to ADCs. I promise we'll get there. Given the magnitude of the PFS benefit, can you talk a little bit more about how much upside comes from moving that treatment earlier, particularly in the symptomatic patients who may not have yet cleared radiographic progression?

Clay Siegall, CEO

Yeah. I mean, look, we would like to help patients the best we can. I think there are a lot of patients that could benefit from this drug, a lot. And the prevalence pool is big in the US, Europe. I mean, it's big. So when you look at the potential market, no one ever gets 100% of your market. But I think we could get a decent chunk of the patients that are suffering if there was a simple, easy to use, effective drug that reduce pain and reduce tumor volume. So we're out there, we're banging on doctors' doors, talking to them. So the first thing, you know, I've launched a lot of drugs, as you all know. The first thing I do is not hire salespeople when I have a real drug. First thing I do is hire medical affairs. So I fill the medical affairs team and I have this team and they go out and they talk to the doctors. What do you need? What are you looking for? How can we work with you? And we don't have our data and go to FDA and you wait for approval and do nothing. You're out there doing small trials, working with doctors. You're out in the field. You're touching base. I mean, you know, when I launched Etcetra's, everyone said, oh, it's going to be a $100 million drug until it became a $2.2 billion drug. So because you're out there, you're talking to doctors and you're listening to them. And that's medical affairs. And, you know, I have a head of commercial for sales and he wants to hire all his sales people today or a year ago. I'm like, whoa, whoa, whoa, that's expensive. We can hire all of those. We'll get those. Let's hire medical affairs first, and let's get a full team out there doing what we need to do ahead of launch. And some companies do it well, and some companies don't do that well. It's not part of their playbook. It's part of my playbook.

Andres Maldonado, Analyst — H.C. Wainwright

Yeah, certainly have a track record for it. So maybe switching gears now to a lot of the ADC pipeline. Obviously, we've looked into Roar One Biology, but amongst the ADCs that we look at a wide breath, ROR1 biology seems to be some of the most attractive and untapped target within oncology. So it would be great for you to start with, you know, describing IM1021 and essentially the core rationale for targeting ROR1 with an ADC, specifically with your engineered Topo1 ADC.

Clay Siegall, CEO

So ROR1 is a very interesting target. It's unusual in that it's expressed on liquid tumors and then solid tumors, a lot of targets are liquid tumor or solid tumor, and ROR1 crosses over. Now, having said that, it's pretty ubiquitous on liquid tumors and lymphomas. You don't really need a screening tool. On solid tumors, it was unknown because you could look at, you know, when you see histology published, it's flawed a lot. And the reason is that if you don't handle your sample well, you crack the cells. And if you look at histology with cracked cells and you say, oh, it stains positive, you might be staining inside the cell and it's not what's on the surface. And this happens all the time. Every scientist knows this. So when you look at a publication and you say, oh, it says 20% staining, 70% staining by groups, they're handling their samples differently. And that's a problem. So what do I do? I always do it myself. And when I say myself, it's not me. It's my great teeth. So it's the royal we, right? And so we do this great work. We came up, we developed a diagnostic tool. Okay. Now that's not my business. Different low margin business. I love other people doing it. So we took our diagnostic tool, gave it to a diagnostic company to make what's called a validated tool that the FDA could say, yes, this is a real tool. You can screen with that. Now for solid tumors, a hundred percent, you need a tool, 100%. Because I can tell you solid tumors is very variable. Some solid tumors don't have expression. Some have low expression. Some have high. If you look at a field and it's 100 cells and you see two cells positive, is that positive? Or if you see 50 cells positive, is that positive? What are you treating? How do you know what to treat? Those are the real story. And when someone just goes, oh yeah, everything's positive, it's not true. You have to look and you have to decide. So we have a validated tool that's almost done. And when that's done, we can actually attack solid tumors. So far, our focus is our liquid tumors because it's ubiquitous. And so that's how we decide what we're doing. But it's an interesting target. You brought up like RoarOne, what's out there? So there's been attempts by a number of companies on RoarOne. And the constructs they've made are interesting. And there's activity. So you have the one construct, and I don't want to blast any companies. One construct is using something that's way too toxic and I think it's problematic. Another uses an antibody that doesn't internalize well and ADC technology that's 28 years old. They can do better. We have the novel ADC technology, a rapidly internalizing antibody. Our ADC technology is outside of resistance, permeability for bystander activity in a heterogeneous population of cells. It's modern. It's excellent. and I am excited about it.

Andres Maldonado, Analyst — H.C. Wainwright

And maybe circling back on some of the forensics of some of the older Roar One programs, I guess, could you ascribe maybe a weight to what essentially went wrong? Was it a payload issue, a target density issue, you know, patient selection or something, you know, just intrinsic about the Roar One biology that they weren't leveraging correctly? And you touched upon it, but really.

Clay Siegall, CEO

Well, the one that's done the most work was a private company, Velos Bio, that Merck bought for 2.75 billion. And Merck did a lot of work in solid tumor. This is not the German Merck that has niragastis. This is the bigger Merck. And they went after some solid tumors, but they didn't have a diagnostic tool. So I'm not blaming them. Without a tool, you're a little blind. You need to have a tool, especially in something that there's such heterogeneity in staining. So you need to have a tool. And so I didn't, they've closed the solid tumor part of their program for a variety of reasons. And you can look that up. Their liquid tumor program, it's still going. I don't fully understand it. I mean, I don't work for them. But I don't, you know, they got with single agent that was well-tolerated in B-cell lymphoma. They have about a 20% response rate. And I could tell you, you know, they're using patients that have failed other therapies. We're using patients that have failed, I call them three plus, and because they've failed three, four, five prior therapies, retuxin regimens, CAR-Ts, other things. And so it's, you know, the hardest patients to treat, but that's what you have to start with a drug. You can't start in front line. You have to start with the hard patients. And so in that population, there are a number of alternatives out in the world that give you about a 20% response rate. And if all we get with 1021, I am 1021, is a 20%, my next comment will be, and I'm closing the program, okay? Because that's not differentiated. We need something differentiated that's going to be, you know, doctors will look at and say, I want to use this in three plus patients because this is a real good drug. So, and I don't know what that people, I mean, I've been asking me, what is that? 40, 50, 60, 70% response rate. I don't have a number for you. You want to see the highest number you can. You want to see it to be safe. You want to see durability. You know, if you see an 80% response rate, it's durable two months, no one will care. So you want durability. You want safety. You want efficacy. We're doing that now. We submitted to ASH. I mean, if anyone tells you they're presenting at ASH, they're lying because ASH has not responded back saying you're accepted. So our intention is to present at ASH. That is an honest statement. And we would like to present data. And my goal is, you know, ASH is a figment of time. My goal is to have the right dose, the right schedule, safety profile, durability, so that then we could treat a lot of patients and bring to the FDA a bolus of data and say, hi, look, we have this. We want breakthrough designation. We want to go and treat, I don't know, 150 patients, single arm, single agent, third line plus, and get approval. And here's our confirmatory study. It's an earlier line, and we're combining it with XYZ. This is the playbook that I've used with Etcetris and PADCEV and every drug I've developed. And it works with the FDA if you bring them differentiated data. So that's the goal right now, find the right dose and schedule and patient population pretreated so that it's a good data set. So we're working hard at that with our World 1 ADC, and we have a lot of ADCs we're developing. So I'm excited about it.

Andres Maldonado, Analyst — H.C. Wainwright

No, this is super exciting. So one thing I want to spend the majority of the time that we have left, at the crux of your ADC platform and all the upcoming ADCs lies this HC74 payload, which, from my vantage point, is one of the most underappreciated aspects of your ADC engineering play. So can you give us a little bit of history lesson on where Topo-1 payloads kind of failed and where this kind of engineering kind of tries to close the gap and go further than any kind of Topo-1 payload?

Clay Siegall, CEO

Look, Topo-1s have been around a long time. If you look at the early patents of CGen from 30 years ago, literally, they had antimitotics, Topo-1 inhibitors, and other inhibitors. So, I mean, this is something people have been looking at for a long, long time. The one that was popular is DXD that came from Daiichi, they have it in HER2. What I don't like about what I was using, the anti-mitotics at CGen, or what Daiichi is using, equal opportunity, dislike, okay, was that both of those are sensitive to resistance. So if you have patients that don't have any resistance, fine. But if you have resistance, and there's a couple mechanisms of MDR, multi-drug resistance, they work much less. And these are data from CGM, Pfizer. These are data from Daiichi. And so I wanted to have a payload outside of resistance. Also, I've treated my mouse tumors for decades. Mouse tumors are all homogeneous. I've treated human tumors for decades. They're all heterogeneous. They're not homogeneous. So you want something that has some permeability. So you can, when you get in the cell, it's not instability. That's different. That's in the bloodstream. When you get in your tumor, you want a little bit to leak out to the local tumor microenvironment so you can get bystander activity. That's really important, especially in solid tumors, more so even than liquid tumors. So you want to have that. And so we made a very permeable drug. Then you want to have drugs that you can conjugate so you don't have much aggregate. Because when you have aggregation, you get lung tox. And look at a lot of ADCs, a lot of lung tox. And I don't, I mean, it could be direct binding or it could be some aggregate or both. And so I wanted to get, I wanted to say, I want to have such low, I don't think you could ever have zero aggregate, but such low aggregate that you don't see lung tox. You don't want to see things that you don't want to. You know, every ADC will give you a little neutropenia. That's what happens. But you can manage that if it's low, but you don't want to start seeing lung tox and kidney docs and all this other stuff. So you want to make drugs that have all the right properties and fix the things of ADCs in the past. So we made a system with H-274. We've actually made it better and better. And, you know, we keep on making it better. So, you know, look, I mean, 28 years ago, I made, you know, the drug linker system that became state-of-the-art, you know, at CGen and made a lot of drugs out of it. But, you know, like I said to you, 28 years ago, They didn't have cars with Bluetooth. So, you know, do you guys drive a car with Bluetooth? Yeah, of course. You know, am I able to make a better drug linker 20 years later? You're damn right. So, you know, we have really good stuff, and we just haven't put out our data yet. And so we're going to be putting out data for one after another after another. And the hit rate, like, we won't have 100% of our drugs. It won't be commercial. But it's going to be a good percent. I feel like we're on the right track with great science and a great team, a lot of exigen folks so while we're a small company we are a very experienced company and and we have our first drug i mean we submitted it got filed we have a padufa date our third year anniversary is next month congrats okay so we're still kind of the child great so with that i think we're up on time but clay um on behalf of myself and the entire hcw team it's been a pleasure and an honor to host you here today and congrats on all the progress number one.

Andres Maldonado, Analyst — H.C. Wainwright

And we look forward to future updates. Thanks.