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 Siegall. Clay, wonderful to see you, as always.
Thank you very much. Enjoy being here.
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?
Sure. 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. Working with lawyers and accountants, maybe not so much of a passion, but making cancer therapies is. I really enjoy it, and what I decided with Immunome is to make a big pipeline and think big. 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. I can go through that in a moment. We have at least 10 ADCs, novel targets, the best ADC technology, in my opinion, out there in the world.
We're pumping them into the clinic, one after another, after another. While doing that, I also wanted to build a company, so I looked at dozens of small molecule drugs. When I ran Seagen for 25 years, I looked around at small molecule drugs, and I brought in tucatinib, which became TUKYSA, in 72 countries approved. A great drug helping women with breast cancer. 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. A lot of the drugs I looked at were not acceptable. I found one, like I did with tucatinib, when I was at Seagen, I found varegacestat. It was, we thought, based on the phase II data, the real deal.
When I look at gamma secretase inhibitors, I looked at it and the varegacestat had great pharmacokinetics, and that was really the difference between that and nirogacestat, which is the only gamma secretase inhibitor on the market. That led us to look at all the data and everything and bring that in. We did all the CMC. There was no CMC done. We invested in it, met with the doctors, got all the phase III done, and the data was fantastic. It's the best drug out there, and we submitted for approval. We're filed. We have a PDUFA date. 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.
It's very similar to the tucatinib story, to bring in a drug with phase II data from a company that was underfunded, no CMC, problematic, but make it into a real drug while I'm working on ADCs. We have tons of ADCs. We even have one radioligand that we're developing, but mainly ADCs. I'm really excited for our future and helping cancer patients.
Great. Before we touch on the ADC program, maybe a couple quick follow-ups on varegacestat. I guess, can you talk to us a little bit more about, given that desmoid tumors are a chronic treatment journey, how are you thinking about the optimal duration of therapy so us, as analysts, can model it correctly?
I have done as much study of desmoid cancer. It is a subtype of a sarcoma. It is treated at SARC centers. They call them S-A-R-C centers around the U.S. And internationally, there are sarcoma centers as well. These are interesting tumors. They do not kill patients. It is like pancreatic cancer kills patients fast. This does not. This is just really painful, really difficult for a patient. You do not want it. You do not want your enemy to have this disease. It is not fun at all. I have talked to a lot of doctors, a lot of patients about it. The pain is the biggest thing in dealing with it. There are 1,650 new patients a year in the U.S., about the same when you look at the whole EU, as a group. There is 11,000 prevalence. A lot of them are doing what is called watch and wait.
Sometimes doctors will give them radiation. Sometimes they will give them SUTENT. None of that, it is just barely doing anything. The first gamma secretase approved was nirogacestat from SpringWorks, now Merck KGaA. That was the first step. When we looked at this, we talked to doctors, and we think about it. In our phase III trial, our average duration of treatment was 20 months. That is something. I will tell you that I have developed a lot of drugs that are a lot approved. In real life, it is always less.
Every drug, I like to lie to you and tell you it is going to be more or whatever, but every drug I have ever made, and that is a lot of them, are always a little less than what you would see in a clinical trial. So I do not know what it is going to be. If I had to guess, I am going to say 16 months, not 20. Something like that. It is not way less, but it is always a little less.
Yeah.
Doctors ask us all the time. They go, "Clay, can we retreat with this? 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?" I faced the same thing with ADCETRIS.
and with PADCEV and all these others. I've done retreatment studies with other drugs, and if you get good data, you get a label for it with the FDA. We listen to doctors. They ask a lot of questions, and we're doing a retreatment study. I don't have that answer for you. I think it's going to work just fine.
Yeah.
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.
Yeah.
They want to know also, how quick is the temporal What's the temporal nature of pain relief? Because that's what the biggest complaint is, the pain. It goes along, pain means tumor. You reduce the tumor, you reduce the pain. So it goes hand in hand, and that's something really important to hear. We've talked to patients. Some of the patients, they go within 2, 3 weeks, "Wow, we feel so much better. Our pain's way down. Within a few months, our tumors are 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. We have developed a single pill once a day.
Yep
That's going to come out, not at the approval, but shortly thereafter.
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?
Yeah. 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 U.S., Europe, 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 reduced pain and reduced tumor volume. So we're out there, we're banging on doctors' doors, talking to them. So the first thing, 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.
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? We don't have our data and go to the 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. When I launched ADCETRIS, everyone said, "Oh, it's going to be a $100 million drug," until it became a $2.2 billion drug. Because you're out there, you're talking to doctors and you're listening to them. That's medical affairs. And I have a head of commercial for sales.
He wants to hire all his salespeople today or a year ago. I'm like, "Whoa, whoa, that's expensive. We can hire all those. We'll get to us. Let's hire medical affairs first, and let's get a full team out there doing what we need to do ahead of launch." 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.
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 ROR1 biology, but amongst the ADCs that we look at a wide breadth, 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 describing IM-1021 and essentially the core rationale for targeting ROR1 with an ADC, specifically with your engineered Topo1 ADC.
Yeah. ROR1 is a very interesting target. It is unusual in that it is expressed on liquid tumors and on solid tumors. A lot of targets are liquid tumor or solid tumor, and ROR1 crosses over. Having said that, it is pretty ubiquitous on liquid tumors, on lymphomas. You do not really need a screening tool. On solid tumors, it was unknown, because you could look at When you see histology published, it is flawed a lot.
The reason is that if you do not handle your sample well, you crack the cells. If you look at histology with cracked cells and you say, "Oh, it stains positive," you might be staining inside the cell, and it is not what is on the surface. This happens all the time. Every scientist knows this. When you look at a publication and you say, "Oh, it says 20% staining, 70% staining by groups," they are handling their samples differently. That is a problem. What do I do? I always do it myself. When I say myself, it is not me, it is my great team. It is the royal we.
Right. Yeah.
We do this great work. We developed a diagnostic tool. That is not my business.
Which is a feat.
Different low margin business. I love other people doing it. We took our diagnostic tool, gave it to a diagnostic company to make what's called a validated tool.
Okay.
That the FDA could say, "Yes, this is a real tool. You can screen with that." Now, for solid tumors, 100% you need a tool. 100%. Because I could 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?
Yeah.
Or if you see 50 cells positive, is that positive? What are you treating? How will you know what to treat? Those are the real story, and when someone just goes, "Oh yeah, everything's positive," it's just not true. You have to look, and you have to decide. 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 on liquid tumors because it's ubiquitous, and that's how we decide what we're doing. But it's an interesting target. You brought up ROR1, what's out there? There's been attempts by a number of companies on ROR1, and the constructs they've made are interesting, and there's activity. 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 is problematic. Another uses an antibody that doesn't internalize well, and an ADC technology that's 28 years old, they can do better. We have the novel ADC technology, a rapidly internalizing antibody. Our ADC technology's outside of resistance. It has permeability for bystander activity in a heterogeneous population of cells. It's a modern, it's excellent, and I am excited about it.
Maybe circling back on some of the forensics of some of the older ROR1 programs, I guess, could you ascribe maybe a weight to what essentially went wrong? Was it a payload issue, a target density issue, patient selection or something just intrinsic about the ROR1 biology that they weren't leveraging correctly? You touched upon it, but really-
Well, the one that's done the most work was a private company, VelosBio, that Merck bought for $2.75 billion. Merck did a lot of work in solid tumor. This is not the German Merck that has niraparib.
Yep.
This is the bigger Merck.
Yep.
They went after some solid tumors, but they didn't have a diagnostic tool. I'm not blaming them, it's just without a tool, you're a little blind. You need to have a tool, especially in something that there's such heterogeneity in staining.
You need to have a tool. 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 is still going. I don't fully understand it. I mean, I don't work for them, but with single agent, that was well-tolerated in B-cell lymphoma. They have about a 20% response rate. I could tell you, they're using patients that have failed other therapies. We're using patients that have failed, I call them three plus, because they've failed three, four, five prior therapies. RITUXAN regimens, CAR T, other things. It's the hardest patients to treat, but that's what you have to start with a drug. You can't start in frontline.
You have to start with the hard patients. In that population, there are a number of alternatives out in the world that give you about a 20% response rate. If all we get with IM-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 doctors will look at and say, "I want to use this in three plus patients because this is a real good drug.
I don't know what people, I mean, have 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. If you see an 80% response rate that's durable two months, no one will care.
You want durability. You want safety. You want efficacy. We're doing that now. Our intent, we submitted to ASH. If anyone tells you they're presenting at ASH, they're lying because ASH has not responded back saying you're accepted. Our intention is to present at ASH. How's that? That is an honest statement. We would like to present data. My goal is, 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.
Here's our confirmatory study. It's an earlier line, and we're combining it with X, Y, Z." This is the playbook that I've used with ADCETRIS and PADCEV and every drug I've developed. It works with the FDA if you bring them differentiated data.
Yep.
That's the goal right now. Find the right dose and schedule and patient population, pre-treated so that it's a good data set. We're working hard at that with our ROR1 ADC, and we have a lot of ADCs we're developing, so I'm excited about it.
Great. No, this is super exciting. 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 aspect of your ADC engineering play. Can you give us a little bit of history lesson on where Topo1 payloads failed and where this engineering tries to close the gap and go further than any kind of Topo1 payload?
Yeah. Look, Topo1s have been around a long time. If you look at the early patents of Seagen from 30 years ago, literally.
They had antimitotics, Topo1 inhibitors, and other inhibitors. 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 ENHERTU. What I do not like about what I was using, the antimitotics at Seagen, or what Daiichi's using, equal opportunity dislike, okay? Was that both of those are sensitive to resistance. If you have patients that do not have any resistance, fine. But if you have resistance, and there is a couple mechanisms of MDR, multi-drug resistance, they work much less in either data from Seagen, Pfizer, these are data from Daiichi. I wanted to have a payload outside of resistance. Also, I have treated mouse tumors for decades. Mouse tumors are all homogeneous.
Okay? I have treated human tumors for decades. They are all heterogeneous. They are not homogeneous. You want something that has some permeability so when you get in the cell, it is not instability, that is different. That is in the bloodstream.
Yeah.
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 is really important. Especially in solid tumors.
Exactly.
More so even than liquid tumors. You want to have that, so we made a very permeable drug. Then you want to have drugs that you could conjugate so you don't have much aggregate. Because when you have aggregation, you get lung tox. Look at a lot of ADCs, a lot of lung tox. It could be direct binding or it could be some aggregate or both. I wanted to say I want to have such low, I don't think you could ever have zero aggregate.
Mm-hmm. Yeah.
But such low aggregate that you don't see lung tox. You don't want to see things that you don't want to. Every ADC will give you a little neutropenia.
Yep. Yeah.
Okay? That's what happens. You could manage that if it's low. You don't want to start seeing lung tox and kidney tox and all this other stuff.
That's right.
You want to make drugs that have all the right properties and fix the things of ADCs in the past. We made a system with HC74. We've actually made it better and better and we keep on making it better. Look, I mean, 28 years ago I made the drug linker system that became state of the art-
Yeah
at Seagen and made a lot of drugs out of it. But like I said to you, 28 years ago they didn't have cars with Bluetooth. Do you guys drive a car with Bluetooth? Yeah, of course. Am I able to make a better drug linker 20 years later? You're damn right.
Yeah.
We have really good stuff and we just haven't put out our data yet. We're going to be putting out data for one after another, after another. And the hit rate, we won't have 100% of our drugs will 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 ex-Seagen folks. While we're a small company, we are a very experienced company.
Yeah.
And we have our first drug. We submitted, it got filed. We have a PDUFA date. Our third year anniversary is next month.
Congrats.
We're still kind of a child.
Great. With that, I think we're up on time. But Clay Siegall, on behalf of myself and the entire H.C. Wainwright team, it's been a pleasure and an honor to host you here today. And congrats on all the progress, number one. And we look forward to future updates.
Thanks.