Ready to get started? Welcome, everyone, to the afternoon session, day one, Leerink Partners Global Healthcare Conference. I'm Andy Berens , Senior Biotech Analyst, Head of Targeted Oncology here at Leerink. Very excited to have with us Clay Siegall, the CEO of Immunome. Thank you, Clay, for joining us.
My pleasure.
Why don't we start with an overview of what you're doing at Immunome, for those that may not know the story?
Sure. Largely, Immunome is an ADC company. We have over 50 novel antibodies we've assembled through a lot of different ways, internal and external. We've prosecuted quite a lot of them and have a big collection of exciting ADCs. We've looked at efficacy. We've looked at safety. Our intention is to put multiple in clinic each year. Today, we announced that one of our ADCs has treated its first patient in phase I.
We really like our antibodies. We like our technology, which we can go through. That's the biggest part of our effort. We have a phase III gamma- secretase inhibitor that we are very excited about and pursuing hard for treatment of desmoid cancer. I'm sure we'll talk about that. We also plan this quarter to file an IND on a radioligand targeted to FAP. That's the crux of the company. We're trying to make a difference in the life of cancer patients through targeted therapy.
You've built the company, and you built your former company out of a mixture of business development and internal development. What do you think is the optimum percentage of internal versus external R&D?
I don't know that there's an optimal percentage. We've done a tremendous amount of diligence on so many different drugs in clinical trials. We looked at a commercial product, a couple of commercial products. We've looked at lots of preclinical antibodies technology. I like to pride myself and my team on the diligence that we do. At Seagen, we did a lot of diligence and did really good deals in bringing in a number of programs. We also, at Immunome, have a really fantastic scientific team.
We have some experts in different areas: antibody sciences, chemistry, clinical development, scale-up manufacturing, regulatory, you name it. We think we have a great set of expertise to develop drugs that make a difference in the life of cancer patients. We're not just looking to just be another cancer company. We want to be serious about this. I've made quite a few drugs that are on the market around the world. That is my total scoreboard, is making more FDA and internationally approved drugs to treat cancer patients in the U.S. and abroad.
That's our intention. We have a big pipeline. As you know, there's a lot of attrition in developing cancer products. Working both internally and externally to bring in technology and targets and antibodies, as well as discovering them internally, is what's needed, in my opinion, to really make a dent in treating cancer patients. I think we're early in the game of targeted therapy. There are many more targets to prosecute and interrogate and develop into great cancer products.
We're excited to do it. We have a great big pipeline. Not everything is a success or will be. Excuse me. At Seagen , I had a pretty good hit rate for commercial success versus molecules going into clinic. We're certainly going to try to do better than that at Immunome. We think that having a big pipeline is essential because not all products work because it's hard to treat cancer.
Right. OK. Bristol used to tout their string of pearls. I think of what you look for as more of diamonds in the rough. How do you find these diamonds in the rough? A lot of them have come from public companies that lots of investors have been looking at and overlooked. What is it that allows you to identify those assets that other people have overlooked?
We don't have the resources to have a string of pearls and pay lots of money for a lot of programs. It is important for us to be able to be efficient. When I was running Seagen , I bought a company called Cascadian to get a product, tucatinib. Now it's TUKYSA available around the world. That company, nobody cared about. It was trading at a couple of two, three bucks a share. Nobody was looking at it. We found a phase II data set we liked. The company was perpetually underfunded.
It had no CMC to speak of, limited clinical development, but really nice chemistry and a really nice phase II data set. Fast forward to Immunome. We looked at dozens of things and ruled them out, dozens, very picky. We found something at a small Israeli and New York-based company called Ayala , which was AL102, now called varegacestat. It is a product that had great phase II data, spectacular. It had no CMC to speak of.
It was a perpetually underfunded company with multiple different CEOs over every year and no real leadership to develop a drug and no way they could develop a drug. They had a great piece of chemistry and great phase II data. It reminded me of Cascadian. We are developing that because we think it could be something that dramatically helps patients. Our heart is, as a targeted therapy company, we're not going to be a cell therapy company.
That's great technology, but it's a different infrastructure build. We're not a gene therapy company or CRISPR company. Also, great technologies, but a different infrastructure. We're focused on targeted therapies, and they could be antibodies, but they could also be small molecules and ligands.
Right. OK. Why don't we—it's a good segue to the desmoid program. How does the molecule that you got from Ayala differ from OGSIVEO, the SpringWorks?
Right. So the molecules are very different. OGSIVEO was originally developed by Pfizer. It was a neurologic disease drug. We have a drug that also targets gamma- secretase. It's an inhibitor involved in the Notch pathway, which is involved in desmoid and other tumor types. The drug we have is 250x more potent. It was developed for cancer. It is once-a-day pills, not twice- a- day. It has more potency. It has different pharmacokinetics.
When you look at the data in phase II that we saw that's apparent out there, the anti-tumor activity was pretty dramatic. They had between 64% and 72% objective response rate based on evaluable and intent to treat patients. We have a median response in patients of 88% reduction in tumor burden. We measured a number of other parameters, such as T2, which is a measure of cellularity, to see if they're really active tumor cells or not, because sometimes it's hard to score them directly based on a screen.
When you look at all of the different parameters, we like these data very much. We think it was--it's a--the data was phase III in the FDA-approved trial for OGSIVEO with a 41% objective response rate. I think it was a 59% reduction in tumor volume. Our data is not phase III. It's phase II. Our phase III study is fully enrolled and enrolled very fast. All the patients are on it. It's an event-driven study. We've guided for the second half of this year. I do not have the data yet. It's a blinded study. I know the study was conducted very well.
I know that the sites enrolled very fast. That's always a good sign. I've done a lot of studies in my career. When studies don't enroll fast, that's always a red flag. This study enrolled fast. That doesn't mean the drug is a success, but it certainly doesn't mean the doctors did not like it. They went back and used it often and often at the center.
We're very pleased with the conduct of the study, the sites, how they're using it, how they're using it in patients. We're looking forward to getting the data in the second half of this year. We think that if the data is remotely similar to the phase II, then we could have a drug that is exceptionally important for patients with desmoid cancer and some other cancer types.
I remember when you acquired Cascadian at Seagen, you made a number of changes to that phase III program, which I thought turned out to be very, very important, especially in the CNS activity. Did you make changes to this program?
The phase III trial was developed carefully. When we acquired this asset, there was about a dozen, roughly, people in Israel that were developing this drug. They were exceptional people doing the work. We have retained them as contractors, which is the best that we can do given all the different jurisdictions people live in. We have had them out to the Seattle suburb that we're in, which is called Bothell. They are contributing very much to the program. I think in the case of Ayala, the phase III was designed very well.
Now, with Cascadian, we had the CMC they tried to do, and it was actually, it was botched. First, we had to undo the mistakes and then redo the CMC so it was harder. With Ayala, the good news and bad news, the good news is that they did not start the CMC, so we did not have to fix the problems. I used to worry that the CMC was on critical timelines, critical path, and that we might have data, and the data is great, but we could not supply the market. That is a real concern.
Investors do not ask a lot about that, but it is a concern of a drug developer like me. I had the same concern with Cascadian, and we made it barely. In this case, I did something that I am incredibly proud of to solve the problem of the critical path. That is, I hired the most important and best drug developer from Seagen, Phil Tsai. Phil is extraordinary. He is actually in India right now. We have suppliers around the world with intermediates and everything we do. It's not only from India, but we do supplies and get materials globally.
We do some from China as well, like everyone does, and intermediates and whatnot. Due to geopolitical activities, it's important for us to look around and make sure we have second sources and everything. Phil Tsai and his team, and a number of them are from Seagen, but not all, are doing a fabulous job.
I am happy to say that we are no longer—the manufacturing is no longer on critical path—that when the data come, we will be able to follow up with regulators like FDA and present our package and move forward and try to get this exciting drug to the marketplace and help patients. That's really good.
That's interesting when I think back to the Seagen days. I mean, you guys were very good at executing on the regulatory path. Once you had data in hand, I think there was never any snafus that I'm aware of. It's good to hear you confident about that.
Just as an example, and investors never asked me this, but with TUKYSA, our data was exceptional. The FDA was going to approve it, and they did approve it faster than we thought. We were not ready with material really to launch. We had enough to treat a certain number of patients for the marketplace. We have new manufacturing coming to have a much bigger storage of it.
We had to put a trial on hold because we wanted to save our drug material to use for commercial. Of course, investors said, oh, you put a trial on hold. There must be a problem. No, it was not a problem. We were trying to save drug to launch it. Of course, the stock went down because we put a trial on hold.
Right. In the program now, are there any differences in the patients that generated the results in phase II versus what you're enrolling in phase III? Are there any differences?
Really, the patients are literally almost identical. It's hard to say that they're different. What is different is how they're scored. For OGSIVEO, it was detection using scanning and radiologic detection, if you will. It was also doctor assessment. For our trial, it's radiologic assessment only, which FDA wanted. It's the right way to do it. It's a third-party radiologic using a blinded group to do this. It's the gold standard, if you will.
I think that it's a little different. I think for OGSIVEO, most of the data came out from radiologic scans. I think only a minority of the data was from doctors giving their sense on it. I don't think it's going to be that much different. It could be a slight difference because it's only using radiologic. That's probably more accurate at the end of the day.
How do the doctors grade it without a radiograph?
Oh, they have their methods to do that. That could be a discussion. It is better to do it through a radiologic method and blinded reviewers.
OK. What did you guys do in phase II?
In phase II, I believe it was both radiologic and doctor assessment. Most of the data is radiologic. I think their data was mainly radiologic. I do not want you to think that it was a lot of doctor assessment. It was only a minimum amount. Our phase III is only radiologic.
Right. OK. What do we know about the [addressable] market based on the SpringWorks launch? What have you guys assessed as the potential size?
Yeah. We haven't really set a size yet. I usually don't give guidance until after you see data. What I could say is, first of all, SpringWorks is doing a great job of launching the drug. Their last quarter was a little bit over $60 million, $61 million, $62 million. I don't know. Their run rate's close to a $250 million . They're only four full quarters in. They're actually doing better than I would have guessed based on the market at this point. I think there's over 30,000 patients in the U.S. that have in the prevalence pool.
Somewhere between 5,000 and 7,000 patients come into the treated pool at different times. I think that if there are better and better drugs with higher response rates, doctors will put more patients on. They also would put more patients on when they get comfortable with the drug and its mechanism and pathway. I remember when I launched ADCETRIS, which was last year's $2.2 billion drug. When I first launched it, doctors had to see, OK, we're going to target Hodgkin lymphoma with CD30. It was a new thing.
We had to teach them how to use it, teach them how to take it up. A lot of doctors pushed back and said, we know how to treat Hodgkin lymphoma. We don't want this new drug. I think that for SpringWorks, they probably have had the same kind of thing that I saw with ADCETRIS, that when you have a new drug, that's the first of its class and first of its kind. There's never been a drug approved for desmoid cancer. They've been using other drugs off label or radiation therapy. Having a first-in-class drug is always difficult.
You have to really teach people about your drug. They've done an excellent job of it, I think. I've seen analysts report saying they think it could be a billion-dollar market. I think that it depends. Are you going to go to the U.S.? Are you going to go overseas? Our trial is in the U.S., Europe, and Asia. We have an opportunity to use data widely if the data are good. I also think that this could be used for other types of diseases, diseases such as adenoid cystic carcinoma. It's not a big disease, but it can add market opportunity. I did this with ADCETRIS.
We added more market opportunities, such as cutaneous T-cell lymphoma, which was small, but it added another $100 million or so to it. Each time you add another label, it adds up sales without costing that much. It is very efficient. I think that there has been a lot of publications by scientists using or trying to use a gamma-secretase inhibitor in combination with BCMA-type drugs. There has been a lot of publications on that. I think that what really could move the needle is a very potent gamma-secretase inhibitor.
Ours is 250 x more potent than OGSIVEO. I think that there is a lot of potential upside to use it in multiple myeloma and other ways. I think the first way and the way we have data right now is in desmoids. I do not want to point to other areas. There are ways. If you look at my history of drug development, I always find other markets and other labels. That's how you broaden out drugs that are important.
Right. OK. You started with the discussion with the ADCs and then went to the desmoid program. I guess that makes me question how important is this desmoid program and this drug to Immunome. Is it something that you would eventually, if you got the right offer from a large pharma company or a spec pharma company, that you would consider divesting and then investing in the ADC programs? How do you think about that?
I'm not going to be exact here with comment. What I could tell you is that I think that the desmoid program could build Immunome into a company worth $2 billion, $3 billion, $4 billion. The ADC program could build a company that's $10 billion +. We have a couple dozen great ADCs. We're just going to pump them into clinic as fast as we can with great data. These are novel, first-in-class, best-in-class type of ADCs. I think that the ADCs will ultimately be worth more. The gamma-secretase is faster.
With the ADCs, we have the ROR-1. We announced that we treated our first patient today. It's the best ROR-1 out there. There are a couple others. The properties of this one, the rapid internalization, the best drug linker, the data is great. I'm convinced it's the best one out there. That's why we're putting our investment dollars there. The next one, we haven't given more targets out, but we've talked about them and presented data. The next one is a solid tumor target. I am not aware of any other company developing for this target.
It's broadly expressed in solid tumors. The one after it is another solid tumor target that I am not aware anybody's done. The one after it is a target that's been in an ADC years ago. It failed, but because that antibody had a very short half-life. We've redone and re-engineered the antibody to have a longer half-life. We made a better antibody, good internalization. The ADC is gangbusters. When you look back at Seagen, CD30 was an old target made ADCETRIS. Nectin-4 was a brand new target.
Now everyone's working on it. It was a new, novel target that no one had really heard about. The other ADC was to tissue factor, which many companies had studied for a long time. The antibody in TIVDAK happens to be an exceptional antibody. You can utilize brand new targets. You can utilize older targets, but make much better antibodies. There are lots of ways to do this. I think you need to, it's a matter of working hard, being persistent, screening for things like internalization, and knowing what you're looking for.
You asked a question about business development. We've hired a Head of Commercial, Roee Shahar. Roee, he was in charge of the ADCETRIS franchise and the TIVDAK franchise at Seagen. He's one of the best commercial people I've ever worked with. He's heading up commercial. We have intention of launching the drug in the U.S. and Canada and Europe as a minimum in what we call LATAM, which is Mexico and South. It's Spanish-speaking sales force. Often you can do that very effectively with a distributor, not a partner.
Distributor, you keep a much bigger part. They're not developing with you. They're just distributing. Also Middle East, we've used distributors before. It's very effective. In Asia and China and Japan, especially, it's often done through partnerships, which they like better than using distributors.
It depends on where it is around the globe and what you do and how you can launch it. That's our intention to launch it. Our intention is not just to get this to approval and then just sell it off. We intend to launch it and grow it and make it into a substantially big product.
Right. I think that's one thing I thought was unique about your company is you've had experience as a drug developer, but you've had a lot of experience as a commercial executor, which a lot of smaller biotechs don't have that experience.
In this case, with a drug like a gamma-secretase inhibitor for desmoid, the work that SpringWorks has done to educate the marketplace is spectacular. If we're so fortunate that our data look great like they did in phase II, the path is already built. That was really great. That's one thing. Another thing is we can do a great job with selling and marketing this drug. It also gives us an opportunity to consider acquiring other drugs for the bag of the salespeople, if you will. I launched many drugs around the globe.
I know we can do a great job. We have the great infrastructure for that. I'm not scared or worried about that. I don't necessarily think selling it off to another company gives us the best opportunity. I mean, at some point, biotechs end up doing one of three things. All biotechs in history, they either go bankrupt, they get acquired, or they become Vertex. And there's very, very few Vertexes. OK, Vertex, Regeneron. Seagen was on the way with billions in revenue.
It could have become the Vertex Regeneron, but went to door number two, which is get acquired. That is what biotechs do. Some of the ones that go bankrupt, sometimes they just go bankrupt. Sometimes they do something called a reverse merger. Whatever you can call it, whatever you want. That is what they do. If you had to ask me what is going to happen with Immunome, Immunome has too many great products in its pipeline. To build a Vertex and Regeneron takes 30+ years . Seagen was 25 years then. What is the most likely outcome?
Getting acquired. How do you get acquired? You get great products. You build great ADCs. You build a pipeline. My goal is not just to flip the company. My goal is to make great drugs for cancer patients. I have made drugs. Some of them come out of my head. Some of them were in partnerships. I've made many drugs that are around the world. My scoreboard is new drugs. I also know that biotechs do not distribute drugs around the world as well as pharmas. If drugs that I make, I could bring them forward a lot.
A company like what Pfizer is doing with Seagen, if they could distribute them around the globe in a robust way, because cancer does not know borders, boundaries, color, anything. Cancer is cancer.
I want to treat as many cancer patients as I can around the world. If we can, and me and my colleagues at Immunome make a great pipeline and great drugs, and someday it ends up in the hands of a really big company that could distribute them around the world and treat more patients, I can be happy. I just want to make a difference in the life of cancer patients. I want to continue doing that as I've been doing.
Right. I have to ask you, is it good or bad for Immunome if the rumor is true about SpringWorks being acquired?
I want the best for all biotech. People ask me all the time, who's your competitor? The answer is cancer. It's not other biotechs. I mean, there's less than 10 ADCs out there in the world. There needs to be 100 ADCs that doctors can utilize alone or in combinations, looking on ChatGPT 5.0 and saying, wow, there's 100 here. I know this and this and this about you. ChatGPT 5.0 will tell you how to treat this. Going to your question, what do I want? I think that when the rumor came out, Immunome stock went up 20% that day.
It's come back since. Would I like them to get acquired? Sure. Not only that, but we all know when acquisitions happen, and I've been part of acquisitions, there's a lot of reorientation and reconfiguration. Maybe that allows us to catch up a little bit. Look, whatever happens, happens. I just want to make great drugs for cancer patients.
Right. Any questions from the audience before we wrap it up? All right. Thank you, Clay. Congrats on all the progress. We look forward to the continuing evolution of Immunome.
All right. Thank you. Thanks.