Great. Good afternoon, everybody. Thanks for staying for our last fireside today. I'm Matthew Harrison from Investment Banking here at Morgan Stanley. Really pleased to have Clay Siegall, the President and CEO of Immunome with us. Just quickly before we get started, I just need to remind everybody, for important disclosures, please see morganstanley.com/researchdisclosures. And with that, why don't we get started, Clay? And I don't know, I guess my thought. I think, you know, just given your background and being in the biotech space for so long, maybe just talk to us a little bit about, you know, the vision for this company, what you're thinking about.
You know, when you've been building programs and thinking about what you wanted to be able to do with this company, how have you been thinking about that?
Sure. First of all, thanks for inviting Immunome to the Morgan Stanley conference. We're delighted to be here and have a great schedule. So you know, the genesis of the modern Immunome, the current Immunome, was I initially joined a private company called Morphimmune, which was more chemistry-focused and worked on radioligands and chemical entities. And the goal was to build that and add in proteins at a later date, and which is exactly what happened, but it was not very much later. It was pretty quick that we decided to put together Morphimmune with Immunome, which is a company focused on antibodies, which I've worked on for many years. And you know, as you know, all the work I've done with ADCs, which is both protein and chemistry.
So I liked having the concept of having both protein and chemistry, and putting that together. So we put that together in October, so it's been about 10 months since we built the new Immunome. We've done a lot of work to build a pipeline. Our pipeline is pretty big, and I'll talk about it today for what we are working on. And in addition to a big pipeline, you know, we now have about 85 employees. We're focused on oncology, and it's targeted oncology that we're really focused on. And we're first and foremost an ADC company, which, you know, I've worked on a lot. I certainly didn't discover what ADCs are. That was years and years ago. But I had a big role in bringing ADCs into the modern world.
And so, what we're doing is working on ADCs targeted to novel targets. You know, 20 years ago, it was important to build drug linker systems, 'cause there really wasn't any good ones. But now, you know, the novel targets are what's important, and to come in with the 20th Trop-2 doesn't make sense to me anymore. And whether it's Trop-2, or HER2, or Nectin-4, these are all drugs, and many I've worked on, that, you know, have real products out there or multiple products, and it doesn't make sense to have all these companies trying to do the next one at this point. What's important now, I think, in ADC world is novel targets, so we have a plethora of them. We have many of them with great packages of data.
We'll talk about, you know, what, you know, what we're looking at going forward there. But in addition to building a targeted therapy company with focus on ADCs, what Immunome is also doing is being opportunistic and looking at doing a lot of different deals, bringing in assets, not just discovering them, which we are doing, and we have an active laboratory building great programs. So we've done seven deals now in ten months, and some of them have been bigger ones, some are smaller ones. Some of them just bring in you know antibody assets. We've done deals with companies like Bluefin, which is a diagnostic company, or a private company called OncoResponse, or another private company called Nectin Therapeutics, and a public company that now doesn't exist, Atreca.
We've also done deals with Zentalis for ADC technology and a lead program. And we've done a deal with- for a small molecule, it's an opportunistic type of deal, with a company named Ayala for a gamma secretase inhibitor. So when I was running Seagen, we did a opportunistic small molecule called tucatinib, which now is available in- around the world called Tukysa. And it's a great drug for breast cancer, where you have brain metastasis, and especially. And so the... That came after development of a lot of ADCs, so no one said, "You're a small molecule company." But now we've done this early, and the reason we did it is because the opportunity was so great. It reminded me of looking at Cascadian.
It was a great piece of chemistry with great Phase 2 data, no CMC to speak of, a perpetually underfunded company with leadership that was changing regularly, and they didn't have a development plan, and so that was really what happened at Cascadian, and that's what the status was at Ayala, but it was, you know, very exciting product with Phase 2, so we did this early on, so certainly our Phase 3 asset AL102 is our lead program at the present time, until we get the large amount of ADCs flowing into clinical trials, so we're gonna continue to pound away on that, and I think that, you know, what investors will see is a lot of ADCs going forward.
Okay, great. Let's come back to gamma secretase. Let's talk about ADCs for a little bit, and then, and then, we can come back to that. So I guess, a couple questions on ADCs. I mean, I think, first of all, obviously, you've been around that field for a really long time. You know, what do you think are the one or two or three most important things to improve on, outside of picking novel targets, which aren't the targets that people have been using? I mean, are there other factors? I think one of the things, when people hear novel targets, that they get worried about is therapeutic window, which has always been an issue with ADCs. So maybe just to, you know, talk about how you think about that and how you think about some of the other nuances that you're focused on.
Yeah. When you look at novel targets, indeed, therapeutic window is everything, but that with an old target or a new target. You know, when I started working on CD30 or Nectin-4, no one knew anything about Nectin-4. Now, it's a known commodity with Padcev. And we didn't know what the therapeutic window would be, but you study it. And if you study therapeutic window appropriately with the right models, which is a function of safety over efficacy, and if you do it with the right models, you could predict a lot. And I've done this. I have quite a few molecules I've made that are on the market now, so I know how to evaluate therapeutic window.
I'm very picky with that, and I have a great staff of, you know, a great group of colleagues at Immunome and, that are, you know, very experienced. Quite a few of them came from Seagen, and they're really experienced in how to develop and understand and identify real drugs and not just something for a publication. You know, what drives me is real drugs and getting drugs on the market, and, I think that that's our goal at Immunome. So what you look for for an... Whether it's a novel antibody or not, is you look for an antibody that internalizes rapidly.
And so when you just pick an antibody and someone says, "I have an antibody to target X," I say, "Well, what was it selected for?" And they go, "Well, I have an antibody." To me, that doesn't mean that much. So to me, you need to make panels, and you need to look at thousands and tens of thousands of antibodies and select for, in high throughput fashion, antibodies that internalize rapidly. That helps to make a good ADC. You also want to do pretty exacting immunohistochemistry on normal tissue to know the relative density on normal tissue versus versus tumor tissue. So you need to know that. And, you know, it doesn't mean that if you have a little bit of normal tissue cross-reactivity, that you can't get a drug.
In fact, most of the targets out there, like Nectin-4, the aforementioned target, does have some normal cross-reactivity. It's just that on tumors, it's much more highly expressed. Now, there are some normal tissues that you need to really stay away from. Like, you know, I've worked on antibodies before that were incredibly strong standing on tumors, but they also stained retina, and you know, you can't go into clinical trials and impact people's vision, and that's, you know, off base, but there are some other normal tissue cross-reactivities that are toxicities that are well worth considering or managing if you're getting rid of the tumor, that won't threaten your life and won't threaten your vision, and so, you know, with any cancer drug, there's always side effects. There is no cancer drug that has zero side effects that I know of.
The question is really, how do you manage your therapeutic window? And can you... You know, some of the old cytotoxics, I worked at Bristol Myers Squibb years ago, you know, more than 25 years ago, and and they had a lot of cytotoxics, and their therapeutic window was small. I mean, very small, like one point five, the difference between, like, efficacy and safety. And with most ADCs, we're looking and trying to look for differences that are, you know, three, four, five X. And I think that is... You know, if you could get therapeutic windows where you could be, you know, three or four times the dose, where you see, you know, you have that much of a range between safety and efficacy, you have a really good chance to be a really successful drug.
All right, great. I think ROR1 is the first ADC target that you have. Maybe just talk a little about why you picked that target, and then, you know, how you're thinking about the payload that you deliver with that, too.
Yeah, so ROR1 is a target that I've been interested in for a long time. You may recall that there was a private company called VelosBio that was developing a ROR1 antibody, and it was my understanding of it, and I looked at this, was that it was a one-off antibody, so it was not necessarily selected from panels of thousands of antibodies looking for internalization. It was just selected as an antibody that bound. And so, and I know that the properties of that antibody are probably not as good as you would like for a very effective ADC. And I know that ROR1's also. It binds to both liquid and solid tumors, which is unusual.
Most antibodies bind to either liquid tumors, lymphomas, myelomas, whatever, and or solid tumors, like colon cancer, breast cancer, and whatnot, and so but ROR1 binds to both, and it was, you know, so by that, it's very interesting. But it binds to liquid tumors a lot more. There's more receptor density in liquid tumors than solid tumors. So if you wanna, you wanna have an ADC that targets ROR1 for solid tumors, you're gonna need to start with a very rapid internalizer. You don't wanna start with an antibody that doesn't internalize very fast, because if you only have limited density of receptor, you need to have some other property to help you out.
So I think that the first molecule that came out, that was from VelosBio, that Merck acquired, and I know, you know, when I was at Seagen, we looked very closely at that, and, you know, was very interested in it, but Merck made a gigantic offer and bought the company. I think based on the data that's come out from that, from Merck, it doesn't look like, at least for solid tumors, that they are progressing on it. They've announced they're not gonna be working on that anymore. And so I'm not sure that that was the right configuration. In fact, I would say I'm more sure it's not the right configuration.
And so the molecule we have was selected based on panels of antibodies and looked for rapid internalization, and is using a drug linker system that's more optimized for solid tumors than what they were using. So I think this is a system that came with a lot of thought and a lot of research, and the preclinical data shows it's a lot better than what was that original VelosBio, now Merck, antibody drug conjugate. So I think we're in a position with ROR1 to be first in class and best in class.
You know, what, what's the plan to prosecute that target? Because obviously, ROR1 is expressed on a handful of solid tumors. So how are you thinking about lead indications, and is there a... You know, what's the strategy in terms of bringing that through clinical trials?
Certainly, based on, you know, the initial ROR1 ADC showing efficacy in liquid tumors in patients, we're not gonna go past that. We're going to treat liquid disease and, you know, hopefully, we can move very quickly into diseases such as mantle cell lymphoma, where evidence of activity was already seen with a different, you know, lesser, you know, a lesser ADC, and so we'll do that, but we're also going to do a basket of solid tumors, and you know, based on our preclinical work, we think we have an excellent chance in seeing real activity in solid tumors.
If and when we see that, you know, we'll do Phase 1a and look at safety, do Phase 1b, looking at specific tumor types, liquid and solid, and then we could judge Phase 2 work based on, you know, evidence that we have from Phase 1b.
Okay. Any timelines that investors should think about in terms of, you know, when you might have initial data here or how to think about, disclosure around some of the clinical data?
So we've guided Wall Street that we'll be submitting IND in the first quarter of 2025 , so soon from now. And, 'cause we're now in the third quarter, so within the next two quarters, we should be submitting. And we're gonna try to beat that as best as we can. You know, I'd love to get this submitted as an IND earlier, and we're working hard to see if that's possible. And the sooner we submit for an IND, the sooner we can get started in patients. The good news with ADCs could be tough news, depending on how you look at it, but if you learn about the efficacy fast, it's not like testing with an IO agent or a vaccine. It takes a while to figure it out. ADCs, you learn quick. And so you kinda know.
Like with Adcetris, we knew by the third cohort of patients that this was a winner. Same with Padcev. You know, and you just know when you see the data, and, you know, you're opening up cohorts in a Phase 1a dose escalation, and doctors are fighting with each other for slots on the cohorts. And then you say, "Wow, I have something pretty good," 'cause that is not always the case. So I think with ADCs, you know pretty quickly. And so the goal here would be to get the IND for ROR1 ADC filed as soon as possible, and then try to quickly turn that around and get it into the clinic. You know, as far as getting data that you can really, you know, sink your teeth into, you know, I it certainly is possible in 2025 to have data.
I don't know, though.
Yeah.
Depends on how quick it can go.
And as you think about other novel targets, I mean, is there any? You know, are you trying to have a new novel target every year, or is there any sort of timeline in terms of what you're trying to achieve in terms of target selection and bringing new INDs?
Right. I think when you look forward, the goal is probably to put, you know, two ADCs, two novel ADCs into the clinic every year. You know, maybe we could do three one year, but I think two is the real goal. And I think based on what work that I have seen that we have and the packages of ADCs we have, I think that is absolutely achievable. And I think when you look only a few years out, we're gonna have quite a number of ADCs in clinical trials because our pipeline is very big, and the packages of data, looking at what you'd said before, the key point, therapeutic index, therapeutic window, looking at safety or efficacy and safety, and looking at the difference there, is critical to what we're doing.
But all the data I've seen that we're working on makes me very pleased that we are on track for many packages for novel ADCs. And so I think we're in great shape. I would say that the number of ADCs that we have within our pipeline has exceeded what my expectations were ten months ago. And I think that we're being cautious with releasing all our data on our novel targets. And the reason we're being cautious is there are a lot of groups, a lot of ADC companies out there now, I mean, dozens and dozens, and dozens. And a lot of them will try to duplicate the work that you're doing in the target and try to go that direction, and it happens all the time.
So what we can do to counter that and protect ourselves is not come as quickly and talk about our targets, but try to file a lot of intellectual property and work with, you know, patent attorneys, and try to cover composition of matter and uses, and get a picket fence, if you will. And then it gives you time also to get a more fulsome package together of data, so that by the time we're out there discussing these data, we've already made internal decisions on development. We've decided to develop it, and we've started IND development, pre-IND development, I should say, you know, you know, you know, in force, and we're going and going forward.
So I think that with the current state of biotech and where it is, in looking at international companies that try to do a lot of this, I think we understand what it is, and we know how to protect ourselves, and we know what's needed, so we may not be coming out with the novel targets as fast as investors want to hear about them, but we will come out and talk about them, and you know, it's. I'm hopeful that by early next year, we'll be starting to discuss some of our furthest along novel agents, and my belief is that the package of information that we'll be sharing at that time will be well received because it's probably a little further along than investors think now.
Okay. Okay, great. And then, I guess, just last question. Anything unique you're doing with cytotoxic payload or any of the other components of the ADCs?
Yeah. I mean, we have a toolbox, and, you know, we look at some of the standard, you know, cytotoxics that are out there, whether they're, you know, TOPO1 inhibitors or whether they're antimitotics, and we have, you know, ways of doing that in our toolbox. We also are looking at some novel approaches, and we haven't come public with what our novel approaches are, but they're very exciting, I think, for a next generation of ADCs. But that's too early to start going public and talking about them yet.
Okay. So as you mentioned, right, gamma secretase is your most advanced program. There's obviously an approved gamma secretase for desmoid tumors. How do you think about that market, the size, and sort of what the differentiation is that you could bring with your molecule?
Yeah. So, the molecule that's out, that's approved is nirogacestat or Ogsiveo, and that's a phenomenal effort by the company that brought it forward. I mean, that was a drug that was initially developed by a pharmaceutical company for neurologic disease. They brought it forward and got it approved, and it's selling well, and it's very impressive work that they've done. We looked at this, at AL102, and we brought it into the company based on the pretty extraordinary Phase 2 data that showed that it was active at three different doses and schedules. And real drugs that really work are active at whatever schedules you do. You could find the most advantageous schedule and dose.
I don't like sometimes when you see these drugs where it's like, well, it doesn't work there, it doesn't work there, it doesn't work there, and works only there. I'm skeptical on that. So what we saw was three different Phase 2 dose schedules, all worked very well, all worked better than nirogacestat, and the best of them worked a lot better. And it had much better, you know, data in terms of, you know, objective response rate and the depth of the tumor reduction, and the T2 score of cellularity, which could measure whether, you know, a tissue is tumor tissue or not, and pain relief, and it's once a day rather than twice a day pills. So I... There was many factors that we looked at in Phase 2.
Now, it was Phase 2 data, it's not Phase 3, so it's hard to compare. But and our Phase 3 is fully enrolled. It enrolled, you know, very rapidly in a robust fashion, and so that tells you what the doctors think of it a little bit. It doesn't tell you that it's gonna be a commercial success, but it tells you that doctors certainly like using it. And I've been involved in many drugs over the years, and some drugs are a tough slog to enroll. This was not. This went fast, and that says something. And, and the Phase 2 data were really good, and there's a lot of doctors that put patients on and put more patients and more patients, and that tells you something.
I think we have an excellent chance at coming out with the premier data for desmoid cancer patients. Now, we'll have to prove that. It's an event-driven study. We've guided Wall Street that we will unblind the event-driven study in the second half of 2025. And so, you know, the second half of 2025 starts in July, you know. So I don't know when it is gonna be, but it could be we could be unblinding in less than a year, or a little over a year, or a little over a year, something like that. And it's event-driven. I've done many event-driven studies in my career, and it's hard to be precise. We now have a few different measuring points, and it's I think the second half of next year is pretty solid with getting the unblinding done.
Hopefully, the unblinding will show data, you know, remotely similar to the Phase 2 data. If it is, I think we'll be, you know, the key molecule treating death by cancer.
Have you shared any other details around the stopping criteria or how that study is powered?
We haven't shared too much about the power and the exact criteria, but it's pretty standard stuff. You know, pretty standard stuff, very similar to what was done for nirogacestat. Not anything crazy.
You know, you're also working on some radioligand products. Maybe just talk a little bit about that strategy, and especially with that target, you know, why you chose a radioligand as opposed to using an ADC there.
Yeah. So we have a radioligand targeted to FAP, which is fibroblast activation protein. And I like- I've liked FAP for a number of years because FAP is on 75% of solid tumors. You know, if... And there are no products on the market for FAP, but if there was, this would be one of the largest market opportunities there is, with 75% of solid tumors. Now, it's on tumor stroma, mainly, and that's the connective tissue holding the tumor together. And so it's hard to get an antibody to tumor stroma that binds and internalizes because it's not really getting into the tumor cell. So in this case, we're using a ligand, and Pluvicto uses a ligand to target RLTs, and it's been helping a lot of patients. That's a Novartis drug. But it's informative because you want a radioligand to clear rapidly.
You want, with an ADC, to use a whole antibody, so you could have retention in the blood. You don't want rapid clearing. And with a radioligand, if you have long retention in the blood, you're gonna get a lot of kidney toxicity. So it is a different construct than what you have with an ADC. So we're using a ligand, which now has a very short half-life and with a radioisotope. And we picked a beta emitter because it has a wide path length. If you pick an alpha emitter, they're very potent, but they just hit the cell that you bind to. And in this case, since we're hitting stroma, we want it to have a wider path length and hit the cells around, so you can hit the tumor cells and the stroma.
And that's certainly, you know, has borne a lot of fruit in our preclinical studies. We also know that the tissue residence time of the radioisotope is incredibly important. And, you know, having said that, you want to use a ligand, so, because it clears quick and you can maybe not damage the kidney, which is the case. If it clears so quickly, you don't get enough that sits in the tumor. So the way you can adjust that is by looking at different albumin binders. And in fact, Pluvicto has an albumin binder. It gives it a little bit more tissue residence time. And, you know, you want to get a fair amount of gray. That's the measure of radioisotope. So you want to get as close to 100 gray as you can, but not hurting the kidney.
We've experimented by looking at a number of different albumin binders, and we know which one we like the most, and it's not the same one in Pluvicto. We've also experimented on a number of linker systems to try to find the linkers that could work the most, that could have the least kidney toxicity. I like the science. I think we've done high science on the RLT configuration, sort of like we did 20 or 25 years ago, doing high science on the drug linker units for an ADC. We ended up with a lead agent targeted to FAP that I think has a fantastic preclinical profile and could be representative of a very important large product.
You may recall that many years ago, Novartis tested a FAP radioligand in clinic, and it was not a great configuration, and it really didn't work well. And then Clovis put a FAP radioligand to clinic, and there were some objective responses. Not a lot, but there were some. It was certainly better than what the first generation at Novartis did, and they learned a lot. And then Novartis acquired that and has. You know, my understanding is they've, you know, they put it in clinic, and now they've expanded it, and Phase 2 is a different study. So clearly, they're not disliking what they see because they're expanding it. But I don't have any set data. I don't think they've put out specific data. But when I see big companies doing work in it, I think that's good.
For us, I'm very pleased that Novartis has expanded that because I think FAP is a great target. I'm hopeful that what they're doing can benefit patients. I think what we have is a premier molecule, and so I'm hopeful Novartis does well with it. I'm hopeful that we can benefit patients. There's so many solid tumors that one can go after and interrogate with these molecules. There could be easily multiple FAP drugs on the market without stepping on each other's toes.
... And timelines there, how should investors think about timelines?
We have said that we will file, we'll submit an IND in the first quarter of next year, and we're on track for that.
Great. Maybe in the last couple minutes, just, you know, you obviously mentioned at the beginning that you've done a lot of BD, I think seven deals in the last ten months, you said. So, you know, how do you think about deploying additional capital, in the near term? Or, you know, how do you think about what your, what your appetite is there?
So BD is an important part of what we have done from our genesis last October, and it remains to be an important part. You know, the way we look at BD right now is we think big, and we're out there looking at the world of biotech, and there's a lot of biotech companies trading at about or below cash. There's a lot of biotech that have really nice programs, but it's more of like a program or a department and maybe shouldn't be a whole company. And there are also a lot of programs that we've reviewed that are really not good. And, you know, we've done a heck of a lot of diligence on programs, and we've walked away from many more deals than we've done.
So by doing seven, that means we've looked at a lot, and we still are looking at quite a few different programs. You know, we would consider acquiring a small company. We'd consider acquiring, you know, bringing in Phase 1, 2, or 3 products. We've even looked at two or three different times, we've looked at commercial products that are relatively small that perhaps meet our needs. We've also looked at, you know, a lot of antibodies and technology that we could bring in, and so we could continue to do those kind of deals. And, you know, like earlier today, I'm you know, reviewing term sheets. You know, a lot of times term sheets don't become deals.
They just are illustrative, and you provide a term sheet to another side pending diligence, and you do more diligence, and deals fall apart a lot. More deals fall apart than you can accomplish, but I would say that over the next year, I expect that we'll be doing a number of more deals, and I don't know whether we'll do seven deals every ten months, but, it's, you know, it's not doing deals to add to our pipeline because we need to. We have a big pipeline. It's doing deals to add to our pipeline because we can do it, we want to do it, and it could really benefit the rapid upward movement of the company.
So maybe just last question, just to remind people, cash position, what the runway looks like, and any other catalysts we didn't mention.
Yeah. We have about $270 million or $275 million of cash. I don't remember the exact number, and that will get us through into, I think, early or mid-2026. So we're doing good on that. I mean, if you look at my track record with Seagen, I certainly raised capital seven times. But we've also did a lot of deals with bigger companies to get non-dilutive capital. And so as we're building a very big pipeline, I think that we could do deals, but we're not pressed to do them. And we could bring in additional capital and keep growing, but we're not pressed to do that at this, you know, this time, because we have a good cash position.
So we'll just have to see going forward, you know, what kind of deals we do, what kind of drugs we're developing, and whether we can get, you know, the kind of data that we want to launch our first product, and then, you know, go forward and show proof of concept and then develop approval pathways for next products. So the goal is to build a nice pipeline of products that can help patients with unmet medical needs.
Great. Clay, thanks for coming. I appreciate the time.
All right. Thank you.