All right, good morning. My name is Michael Schmidt, Senior Biotech Analyst with Guggenheim. It is my great pleasure to welcome Clay Siegall, CEO and Chairman of Immunome. Welcome, Clay. Thank you for joining us.
Thank you. Thank you for the invitation.
Clay, Immunome was initially put together through a series of mergers and acquisitions. Could you just remind us of your approach to how you're building the pipeline at Immunome?
Sure. So the pipeline that we have is focused on targeted therapy for oncology. And we don't do everything. We are pretty focused on the kinds of technology we use. We target the cell surface with a variety of molecules. We also target the inside of the cell with small molecules. We do not do cell therapy or CAR-T or other ones, all exciting technologies, but a different infrastructure. So our infrastructure is focused on small molecule and cell surface targeting.
Great. Let's maybe jump into some of your pipeline programs. Very exciting data, obviously. Your gamma secretase inhibitor recently reported positive phase III data in desmoid tumors late last year. Maybe first, how do you think about the opportunity in desmoid tumors and the size of the commercial opportunity?
Yeah, so we did a lot of diligence. We wanted to build some targeted therapies for the cell surface. We looked at about 20 different companies and focused on trying to figure out if there's something we can in-license. I've done this in the past and did extensive diligence at Seagen. I did a lot of diligence and ended up acquiring a company for a drug called Tukysa, which was a great drug as a small molecule. When you make ADCs, you have to build both a biology team and a chemistry team. A lot of biotechs are one or the other. I have to have chemists and chemistry manufacturing and biology and biology scale of manufacturing.
So it enables me to do deals and bring in molecules that could be antibody-based molecules like an ADC or a bispecific, but it also enables me to bring in small molecules. So we looked at about 20 or so companies, did a lot of diligence. I'm very picky, as many of you know, as to data. I really liked this drug. It reminded me of Tukysa because it had very good phase II data and it had no CMC to speak of. It did not have a really good. They were going through a lot of different leadership at the small company. They were perpetually underfunded. They didn't know really how to do a phase III. I really liked the phase II data. I liked the chemistry. So we brought that in. The data is spectacular.
We will be putting out. We only put out top-line data. There's about 10 endpoints, primary, secondary, tertiary endpoints. We put out three of the endpoints. But on the top 10 endpoints, we won on all of them. So I mean, I'm very thrilled with the data. So you ask a little bit about the market opportunity. Desmoid carcinoma is. It's a type, a subset, if you will, of sarcoma. And it is a very painful disease, to say the least. There's a small amount of new ones in the U.S. U.S. numbers are about 1,600 a year in the U.S. But there's about 11,000 prevalence patients that come into therapy each year and are looking for something. And there's actually more than that in the prevalence pool. But some of them don't come in for therapy. It's almost 30,000 in prevalence.
About 11,000 in the US look for something. We think that between the new patients each year and a good chunk of the prevalence patients, we could have a very substantial drug. We've not provided guidance yet, specific guidance. So I don't want to start that today. I've developed and launched many drugs. I usually don't provide guidance until for a little further on. We're planning to submit within the next few months to the FDA. We're hopeful that the FDA moves quickly on this. Our hazard ratio was 0.16. FDA should not have a problem with that in my career. Of the many drugs that I've put onto the market, developed, my previous record for hazard ratio was 0.22. I'm very happy with the new record of 0.16. It's going to be hard to beat.
But I think that this will have a substantial market opportunity. And keep in mind, too, using the price that SpringWorks set, OK? And we haven't set our price. But using that price for the drug, you need about 3,000 patients to have a billion-dollar market. So what I'll say, and do I think 3,000 patients are obtainable? I absolutely do with a good drug. And also, we're working closely with doctors to try to figure out how they want to use the drug. And when you listen to doctors and how they want to use it, it's just a difference between you develop a drug, but then you make a medicine. And I know that may sound the same. But doctors will you talk to doctors. They say, look, your dose that you're using is 1.2 mg per day.
We have to take patients that have these big tumors. They're very painful. We have to debulk them. We have to make them much smaller. We have—I mean, almost every patient on this drug has a smaller tumor and really gets debulked. It's very effective. Then they say, but we want to keep patients on. Most cancer drugs that I've ever worked with have some side effects, especially over long periods of time. Doctors say, look, we want to keep people on. Maybe it'll be a year or a year and a half. We'll do great with them. But we would like to go down to 0.9 from 1.2. Maybe if we keep people on for another year, we want to go down to 0.6. It's almost like a maintenance dose.
They're like, how could you work with us and help us? So I have to go from an approved drug to what's a medicine and how do doctors want to use it and how do they want to keep patients on and do best by patients. I go out and I meet patients. I meet different patients. What you hear from them is they might have a big nodule, I mean, big on your neck. One patient had a big thing on her neck. Her arm was paralyzed. She couldn't move her neck. They want to do simple things from cancer therapies. They want to go to the grocery store. You don't think about that when you're not a cancer patient. But if you can't move your arm, you're paralyzed on one side.
You want to get that tumor gone from your neck. You want to become a normal person. So that's where you have to make a medicine that really helps the patient and not just an approved drug and walk away. You want to listen to docs. We are working really hard with docs. We just hired the number one, in my opinion, medical affairs person in the United States who I worked with for many years at Seagen. I am thrilled with that to go out and lead the effort of medical affairs, which is different than clinical development. We have good people there, too, great people.
Yeah, that's maybe a follow-up question. Obviously, desmoid tumor is an interesting space. Ogsiveo is already on the market, same mechanism of action. Maybe talk a bit more about perhaps early feedback from physicians, how they think about varegacestat relative to Ogsiveo. And how do you think you could break into the market? What are some of the key features of varegacestat that make it perhaps the preferred therapy in the space?
Yeah, well, we, first of all, have a much higher ORR, objective rate of objective anti-tumor regression rate by FDA standards. So we have a much higher median tumor regression rate. We will present our data on pain relief. In this disease, it depends on which cancer you have. In this one, pain relief is incredibly important. We'll be presenting data on pain relief at conferences. It's very effective. I mean, there's just so many different endpoints you can look at. It's once a day, not twice a day, like the competitive product, which is easy. We've went out and we've interviewed doctors and patients. In fact, with doctors, they started coming to us. They would say, if your drug is as good as the other drug, we're going to switch to do once a day. We were like, why?
It was a little surprising at first. They said, because the compliance is not great. We went out and started interviewing patients. We heard from patients that, yeah, we take it once a day, sometimes twice a day, sometimes once a day. Doctors are like, we really want to have a once-a-day regimen and get better compliance and better pain relief and better anti-tumor data. I think that we have out in the market, obviously, if you're a patient and you're responding to nirogacestat, you should stay on it. That's the SpringWorks product. We would never tell a patient that's responding and doing well because we're focused on patient care. Anybody who's responding to a drug shouldn't switch a drug.
But if you're not responding or you're a new person coming in or you're in the prevalence pool, those are, to me, very fair game to start with. With enough time from patients that are on drug, the other drug, and getting off, we think we could command a big chunk of the market. I don't know why a patient would even take the other drug once our drug is approved because it's so much superior.
Yeah, and I think Ogsiveo is on a sort of $320 million annualized run rate right now. Any learnings from the Ogsiveo commercial launch? And how do you think you'll approach the launch pending approval in the U.S. and then the rest of the world as well?
It's hard to speak exactly to it. I have some inferences about what they've done. I know what I've done in the past with drugs. I know the premium that I put on medical affairs. That's interacting with doctors. It's going out there and listening to them and hearing what they want and follow-up studies to look at how best to use this and what are the right doses and what's the temporal nature of pain relief. What can they tell their patients? Sometimes you go out and you do. Doctors are like, "We really want to know how quick your pain relief is in this type of patient." You might do a 30 or 40 patient study while you're waiting for approval.
You're working with all the doctors and doing studies to get them answers for what they want so they could have a better medicine for their patients. It's getting out there and pounding the pavement with medical affairs. When I launched Adcetris, your friends on Wall Street and I don't think you covered Seagen then at that time. But your Wall Street brethren said Adcetris would be a $100 million drug because it's for a small indication. And Adcetris, it was over $2 billion. So how did it get there? What happened? Well, first of all, you go and you get out there. Medical affairs are really important in talking to doctors. Second of all, you look at whatever indications are possible. There are other indications that are possible and other uses for this drug.
You get out there and listen to what doctors want, patients want. You make the drug available. I think that we're going to have a great time selling and marketing our drug, varegacestat. We do have a really great name for the drug. I can't say it yet. I really like it.
OK, great. So remind me, how are you tracking towards NDA submission? What have you said around timing for NDA submission?
Oh, so we got our data right at the end of the year. So it was in December. And I immediately go and talk to the team. And you look at what a lot of companies do. And it usually takes 6 months or so to submit a first package. And the reason why when you have second indications, it's less. The first package has all the manufacturing and the QCQA. And so there's a lot there. And so the team at Immunome said 6 months. And I said 4 months. And they said 5 months. I said 3. And they go, OK, 4. And so we're negotiating on how fast. And the team is cranking. I mean, it's literally they are doing a great job of getting everything together. And you don't want to do it to the point where haste makes waste.
You don't want to make a hasty package to the FDA that the FDA looks at and goes, "Well, I can't follow the package." I know from my experience at Seagen, our FDA-submitted packages were always really, really good. FDA used to thank us for making packages that are, with all the modules you have in there, easy to find information. So it's really important to make this. I mean, FDA reviewers are people. They're not just throwing whatever they want. You want to give them something that they can really look at and really find the information. So we're working hard at that. I mean, our head of clinical development, Chief Medical Officer, head of regulatory, head of clinical operations, these are all ex-Seagen people.
And so we're not talking while Immunome is a little company, the expertise at Immunome is equivalent to a much larger company. And I'm very proud of that. I'm honored by that I have so many people from ex-Seagen, Pfizer, that want to come do it again. So it's an honor I have every day.
Great. It sounds like NDA submission coming soon, basically.
We're working hard at it.
OK, perfect. So I did want to switch gears and talk a bit about your ADC pipeline. Obviously, your background in the ADC space is well known. And so maybe starting about talking about your lead program or your most advanced program, IM-1021, which targets ROR1. And maybe, first of all, what makes ROR1 an interesting ADC target? And what have learnings been to date in the industry about it?
So I'd love to talk a little bit about ROR1 and then the rest of the pipeline. But maybe start with when I started thinking about ADCs. This is a long time ago. This is like 28 years ago. I did not discover ADCs. They existed. There was some early, I'll call it, pioneering work of some molecules that used natural product drugs. They used antibodies that weren't great. And they used linkers that were not very stable. And so when I looked at this and this is from starting in postdoctoral fellowship after I got a PhD. And then I went to Bristol Myers Squibb and was a scientist. And before I founded Seagen, I looked at antibodies. And I was like, antibodies by themselves can make drugs, Herceptin and Rituxan. But most antibodies on their own aren't potent enough. And so making empowered antibodies could be really important.
I started thinking about ways of doing it. They weren't really called ADCs. I actually named them ADCs. I should have trademarked it and got a nickel for every time someone said ADCs. I started publishing and calling them antibody-drug conjugates. I like to say that I developed and I was the lead person developing ADC 2.0 because 1.0 was already there and with stable linkers, with synthetic drugs, which was really important, not natural product drugs, and the right engineered antibodies and conjugation technologies and all that. A lot of the rulebook that I laid out over the last few decades are being duplicated. Now there's more than 100 companies working on ADCs using that rulebook. Now I have another opportunity to do well by patients.
So we sat back and said, OK, what is it that we want to do? Do we want to just do more ADC 2.0? Or do we want to do ADC 3.0? So we looked at what's wrong with ADCs 2.0. And I know that probably better than almost anybody. And I've put a lot of ADCs on the market. So I understand this. One of the things that always bothered me about ADC 2.0 that I made, my own problems, were that they were sensitive to resistance pathways. So if you go into patients and whether it's with this Seagen-Pfizer molecule, whether it's DXd from Daiichi, those are the two big workhorses of ADCs. Both of them are sensitive to resistance pathways. So you go into patients.
You have a much higher response rate if the patients don't have efflux pumps, P-glycoprotein being one of them, things like that. And so they pump the drug out. So I wanted to go to the next level. I wanted to use payloads that did not get pumped out. That's an example. Another one is every time I set up with my team a mouse model with a human tumor in it, that's a homogeneous tumor. And after decades of working with human patients, you don't have homogeneous tumors in humans. They're heterogeneous in almost everyone. So what's really important is something called bystander activity. You want to kill the cell. But you want to kill the cells next to it.
One of the things that I wanted to do was have a payload that was more permeable so it could hit a few cells around it, not fall apart, not stable. That's a different thing. Stability is in the bloodstream when you administer it. Permeability is after it gets internalized into a target cell. Could it get out of that cell and hit a few cells, a short path length of cells around it in the local tumor microenvironment? Some people call it the tumor milieu. We worked with molecules that have permeability. There's a whole bunch of other things like the linker and just stability and how it's released and other things. We went ahead and designed all sorts of features in ADC 3.0, put it together. In animal models, the data was really, really good.
In models of heterogeneous tumors, it's really good against models where you get the drug pumped out. It doesn't work with either the Seagen, Pfizer, or the Daiichi molecules. Ours worked beautifully well because it wasn't sensitive. So then the idea is, OK, let's take that to clinic. Let's prove it. So we're in the clinic with our very first one that targets ROR1. It's called IM-1021. It's the molecule. We're doing dose escalation, looking at dose and schedule, which is standard and safety, which is standard phase one stuff. We have reported a little bit. We've said that we've seen objective responses at multiple dose levels. So far, I'm very pleased with the results. The results have exceeded my expectations for the beginning of phase one. The goal and challenge with any new ADC is getting the right dose and schedule.
And I'll give you a very short example of that. When I developed Adcetris, we had no idea the dose and schedule. It was the very first of the ADC 2.0 that we made. So you come out. And you do weekly. And you see some responses. You do every other week. You see responses. You see safety. And what we realized was the half-life of Adcetris was sufficiently long that if we did weekly, you were getting overlapping toxicity. And you get more neuropathy and other things. But when you did every third week, you maximized the efficacy and minimized the safety. And every third week was what was used clinically. I mean, that's approved by FDA. So we come in with a new drug. And you have a lot of predictions. But until you go into humans, you don't know.
Padcev, which was another drug at Seagen, we came in, OK, let's do every third week. Well, then we went in. We find out we have a short half-life. So Padcev's dose, to cut to the chase, is week one, week two, drug holiday, week one, week two, drug holiday. So now we have new ADCs. And you have to really test. And so we're taking 1021. We're figuring out everything. We're looking at efficacy, safety, dosing, pharmacokinetics to maximize it. I know it's active. I know it's active at multiple dose levels. That is thrilling to me. Now I want to make it into not just something that's active because I don't really care about coming out. I mean, I've made so many drugs. I don't want to just say, here's another drug that's active.
I want a drug that's approved and that's maximized to the end and bringing to FDA to get approval. That's my scoreboard only is drugs that are approved. And so I want to maximize this drug. And then we'll put out the data at a clinical center. And then this year, we're going to submit 3 INDs, all for solid tumors because ROR1 is the first one. That's mainly an antigen for liquid tumors. It's mainly lymphomas, B-cell lymphomas. It does have some solid tumor expression. To me, the work that's been done in the past on this for solid tumors was done without a diagnostic tool. Kind of I feel like you're blind because it's only expressed on a small amount of solid tumors. We have a diagnostic tool. So I think we're in better shape than anybody else on that.
That should start later this year because that diagnostic tool, we're still finalizing the tool and just making sure it's all good. It exists. It just needs to be qualified. So we're really happy with our ADCs and the future ADCs coming out as well. They're really exciting.
On the ROR1 program, I know you've made comments about seeing responses, et cetera, recently. How are you tracking towards identifying a recommended phase 2 dose at this point? And what dose expansion course are you planning?
Yeah. So we just added, I think, 6 or 7 U.S. sites and other 6 or 7 or 8 European sites. So by all I mean, if you want to know, are we expanding the work we're doing in 1021, the answer is yes. We've not put out a lot of data except to say it's active. But I don't like wasting time at all. I want to make drugs for cancer patients. So we are putting more money into it and expanding it. We've seen multiple objective responses at different dose levels. So that's about the best I could say. I really want to retain the data that we have so that the doctors doing the hard work can stand on a podium and present the data at an appropriate conference. But we are expanding what we're doing with that drug.
We get asked a lot about the program. To what degree does the data and lymphoma, you think, validate the platform and validate the payload that is also being used in your other solid tumor programs?
You know, it's kind of interesting. The platform that's on and our technology that's on the lymphoma drug, IM-1021, the first one, I really, really, really like. And it's going to help validate it when our data comes out to the world looking at it. We did tweak it a little bit for our next three. So we are constantly improving. We're constantly trying to get better. We're constantly looking at different ways of making ADCs better. So now the tweak is not massive. But we did make a change on our next ones, which we'll talk about more. I haven't talked about it much. I don't want to sully IM-1021 by this. But we're constantly trying to get better and better. And I think, especially for solid tumors, you've got to be on your A game.
When I look at lymphomas, there are three main types we're going after with 1021. We're going after diffuse large B-cell, which is the biggest of all the B-cell lymphomas. We're also going after mantle cell lymphoma and follicular. I don't know. It could be three separate trials at some point. Right now, it's in one trial. I don't know. I can't tell you yet whether we're going to go after all three for approval. Sometimes FDA likes when you focus. Like with Adcetris, we did a separate trial for Hodgkin lymphoma and one for T-cell lymphoma. And it enabled rapid approval because we were very focused on specific types of lymphoma and not just a general bundle. So I would think that those three B-cell lymphomas and there's other B-cell lymphomas like marginal zone and whatever.
But we're focused on those main three and maybe two. I don't know. Well, to see how we can go fast and get on the market. It doesn't mean we won't go and try to go to all three or all of them. It's just how quickly can you get on the market and help patients? And how quickly can you get to where you're doing in lymphoma combination studies in first and second line? Because our first approval, and I think that we have a great shot of going after it, is going to be in patients that have been treated with, I call it, three or more. That means at least three prior therapies. And it could be Rituxan, CHOP. It could be CAR-T. It could be anything. But we see in our studies, we have three or more. Some patients have five or six prior therapies.
That's first approval. I've done that with almost every drug I've made. First approval is the patients in the most need. They've either responded and then failed or failed. They really need something. So that's our first approval. But then you work your way toward front line. It becomes much bigger of a medicine for patients than just a first approval.
Yeah. So it sounds like do you see an accelerated approval opportunity for the program?
Absolutely. I see an opportunity for that. We're not ready to put out our data. We're trying to maximize this drug for patients. But I'm very excited about the opportunity with this drug.
OK, great. Awesome. So our time is up. So we didn't get to talk about your radioligand therapy, which is starting phase one as well. But we'll touch on that next time, I think.
Yeah. The radioligand is cleared by FDA and going to start in clinical trial soon.
Great. Well, thank you, Clay. Appreciate the time.
All right. Thank you.