Great. Good afternoon, everyone. I'm Andrew Berens, Senior Biotech Analyst at Leerink Partners. Thank you for joining us on day two of our Global Healthcare Conference. We're really happy to have Clay Siegall, CEO of Immunome. Thanks for joining us, Clay.
My pleasure.
Why don't we start with a brief overview of Immunome for those who may not be familiar with the company?
Sure. We're an oncology-focused company working on targeted therapies that are either targeted to the cell surface through antibody or ligand-mediated targeting, or targeted to intracellular specific pathways using small molecules. Either way of targeting the surface or inside the cell, our goal is to make a difference in patients' life with cancer, and we have a very big pipeline and excited to talk about it.
Great. Why don't we start with the lead program? You're about to be a commercial company in desmoid. What can you tell us about the data and, you know, and that opportunity? There's one approved drug that's similar, but your data looks stronger. Can you give us an overview of where you are with the desmoid program?
Sure. We've been developing a drug called Varegacestat. It's a gamma secretase inhibitor, and it's an important driver that inhibiting this pathway, you know, is very important to treating desmoid cancer. It's a targeted therapy. It targets the inside of the cell. A number of years ago, there was a different molecule developed called nirogacestat, and it's a pioneering molecule. It's a first-in-class developed for desmoid cancer. You know, some excellent work was done on it to develop this molecule and bring it forward and get it approved. The reason we developed Varegacestat is we believe that Varegacestat has better properties and much better pharmacokinetics, and it's a better piece of chemistry for patients. We've developed it.
We went all the way through and completed a phase III trial, which we announced in December, and the data was fantastic. We had a hazard ratio of 0.16. I've developed a lot of drugs in my career and brought a lot of drugs on the market. That was my all-time best hazard ratio, lowest hazard ratio, if you will. We only put out some top-line data so far, and the full dataset will be put out at an upcoming oncology conference. We submitted to this conference. They have not sent out their acceptances yet. We hope to be presenting it mid-year. There's quite a lot of primary and secondary and tertiary endpoints that are important.
Only a few of them were released in top-line data, so there's a lot still to be released. I am confident that when all the data is released, I think doctors will really appreciate the data. It's outstanding, and I think investors will also look at it and think it's outstanding data. We're looking forward to submitting to FDA. We recently, you know, met with FDA, discussed our NDA submission. I think I feel very confident that the team at Immunome has it very under control, all the modules for the NDA submission, and we hope to get that done. We've guided Wall Street in the second quarter, but, you know, hopefully sooner than later. Second quarter starts next month, so we're hopeful to get this going fast.
It's in the FDA's hands to review, and we are excited to try to commercialize this product. We have a fantastic head of commercial, who you know, he worked with at Seagen with me for a long time and launched many drugs, so he's a very talented guy, Roee Shahar. Our manufacturing on this product was a heavy lift, but our head of manufacturing, I worked with at Seagen for almost 20 years, Phil Tsai. We have some great people working from regulatory to manufacturing to commercial to clinical to medical affairs. We're poised and ready to get this onto the marketplace at some point. We hope toward the end of the year or early next year, depending on when the FDA responds.
We are ready to go and ready, you know, to bring this to patients that are in need. We think this drug has so much data that we haven't put out yet, but the data that we have put out shows that it's a much higher response rate with a much deeper antitumor, median antitumor activity, tumor reduction. There's, you know, it's once a day, which is an important aspect of this drug. We're really excited with this. We think we'll be able to get this drug to patients around the world. We have a great plan.
We're gonna try to commercialize it ourselves in the U.S. and Europe and Canada, and use distributors in Latam, that's Mexico, Central, South America, distributors in MENA, which is Middle East and North Africa, some big countries, and then probably, you know, have a partnership with a company in Asia. That's how we're gonna get it around the globe as a relatively small biotech, and I think it'll be very done very effectively, cost effectively and efficiently in order to have the biggest possible market. We've not guided yet on the price that we're gonna charge. We've not guided yet on exactly what the market opportunity is, you know.
We price it similarly, which we don't, we haven't said yet, if you use the price of nirogacestat, which is out there on the market, if you treat 3,000 patients, you have a billion-dollar drug. It's a, you know, potential substantial market that's opportunity.
Great. Well, I'd like to dig in a little deeper into some of the things you said. I mean, you've obviously launched a number of drugs, very successful drugs in, you know, for a size biotech company or immuno-onc, you probably have more experience than maybe any CEO that's ever been in this situation. I'd like to dive into, you know, attributes about the drug that you think are gonna be beneficial, going against the Merck KGaA drug, and then strategies, commercial strategies you think could be improved upon what they've done, that you think you'll be able to do better. Why don't we start with the, I guess, the drug's properties.
Well, I think that gamma secretase is a great way to inhibit these tumor cells from growing and proliferating, and I think that the target lends itself well to the drug that was first made. That drug, Nirogacestat, has some properties with pharmacokinetics that are less than you would want, so it clears very rapidly. As a result, they need to use it multiple times a day. They use 250 times more than we use in a day, 300 milligram versus 1.2 milligram. Our pharmacokinetics are substantially better. It stays above trough value. It keeps its activity, so once a day is fine to do that. That's a big advantage, more so than we thought.
A lot of patients will take it once a day or twice a day or whatever, Nirogacestat kind of forget. It was a little surprising when the doctors told us how important this was, but we had done this and interviewed patients, and certainly it is true that once a day is gonna be a lot better and a lot more adherence to the right protocol and the right aftermarket use. We have a much higher response rate, a much deeper anti-tumor response, and I think it's, you know, large part due to the much better pharmacokinetics.
Okay.
I think that if you said, "Clay, what is the one reason why your drug is better than the alternative?" I would say it's the pharmacokinetics.
Let's talk a little bit about the disease. These patients have tumors all over their body, and a large part of their, besides being disfiguring, is pain, right?
Mm-hmm.
It's important to act quickly and reduce the density of these nodules everywhere. Is that one of the things that the physicians have been saying is having reduction in pain quickly?
That's probably the most important. That's probably what we hear about the most from physicians is, that patients have a lot of pain. It's painful. It's disfiguring. It's not life-threatening like some other cancers are in that degree. You know, pancreatic cancer is fast and life-threatening. Where desmoid, you last a long time. It's the pain and the disfigurement that really impacts people's lives, you know, and progressive cancer, of course. We have studied in our clinical trial pain and pain relief, and the data, I think is fantastic, will be reported in the full data set at the conference. I'm very pleased with how well we did on the pain reduction index. You know, I can't talk about all the data yet, but soon enough.
You are right that doctors ask about that a lot. I think that will help us in keeping patients on drug because, you know, we've been asked a lot by investors about discontinuation that's been seen with Varegacestat. You know, while I can't, I didn't launch that drug, and I can't give you an exact answer, it certainly is important to have pain relief and continued pain relief for patients, and it'll ensure, you know, they'll want to stay on it longer, for sure.
Okay. I guess in terms of some of the commercial strategies that you've seen Merck KGaA leverage, what do you think can be improved upon?
Well, I think we could treat a lot more patients. I think there's 1,600 newly diagnosed patients in the U.S., about the same amount in Europe, and even more so in the rest of world, with real paying customers, whether it be, you know, Asia, Middle East, or LatAm. There's plenty of newly diagnosed patients. In the U.S., there's almost 11,000 prevalence, not just the incidence, but the prevalence patients, and a lot of them come in and out of therapy. I think if there's a really good drug that really reduces pain and is easy to use and well-tolerated, I think a lot of patients will want to use that drug and come on to therapy.
We think that there's a real opportunity here to have a lot of patients come on and stay on, and some of them for multiple years. Certainly we've seen patients being on, you know, experimentally in our trials, patients can be on for multiple years. Now, there are times where docs will use our drug at 1.2 milligrams, and if a patient's on a long time and we have a median reduction in tumor burden of, you know, high 80s, so most patients have much of their tumor reduced. At some point, some docs like to because all cancer drugs have some side effects, and I've worked on many for decades, and I'll have some. Doctors like dose reducing if they can, especially if you're staying on for a long time.
We've had doctors dose reduce from 1.2 to 0.9 per day very effectively when they have a lot less patient tumor burden. I think that this is a very doctor-friendly and patient-friendly drug that we have with really high, you know, response rate, high degree of reduction of tumor burden, and other primary, secondary, and tertiary endpoints that you'll see at an upcoming cancer conference.
Well, the drug will be supplied in what doses?
Well, right now, the initial drug will be launched with a bottle, and there are pills at 0.3. You take four pills once a day.
Okay.
If, you know, let's say after a year they want to dose reduce, it's very simple.
Okay.
We are working very hard on blister packs with pills in it, and they'll have weekly blister packs. You can have four-pack, that's like a month. We're doing pills, single pill a day at 1.2, 0.9, and 0.6.
Okay. I think that the fact that patients do take a drug holiday does give you an opportunity for the patients to be switched, that might have been on the Ogsiveo. Gives that opportunity for doctors to say to their patient the next time they need a drug, you know, "Why don't you try the new one, you know, see what you think." Are you getting a sense that could happen?
Well, I think that, you know, I've launched a lot of drugs, and I never have gone to my commercial team and said, "If a patient is responding to a drug, you should try to get the doctor to switch drugs." I'm not sure that's exactly what you're saying, but I-- that's not something that is within me. I'm pro-treatment of cancer patients. If they're taking, and I don't care what drug it is that I've developed, if somebody's really responding to a drug, they should continue on the drug. Now, with the amount of new patients diagnosed and all the prevalent patients, and you look at Europe, you look at everything, there's tons of patients that are not gonna be treated with nirogacestat. The response rate nirogacestat, you know, is much lower than Varegacestat.
Any patient that is on nirogacestat and fails are certainly fair game to use the drug, and any patient that's not been treated should use it. We think we're gonna start capturing very quickly, you know, almost all the frontline patients and, you know, first treatment patients 'cause it's a much better drug, and we're gonna start capturing a lot of the prevalence patients that wanna come back into therapy because they're in pain or need therapy. I think that the amount of patients that are on drug with nirogacestat over a pretty short period of time will probably start diminishing and won't be a big population. I don't think it's gonna matter that much.
Right. Okay. I guess in terms of. Yeah, I mean, I wasn't saying that you should take someone off, but if someone stopped and the doctors had a good anecdotal experience.
That's between the doctor and the patient.
Right. Okay. Do you have a sense for what the real world usage will be for these drugs? Like, how long do you think patients will stay on them?
You know, our average patient is on, you know, for now and we're tracking it about 20 months. I think that if we do a good job with medical affairs and we talk to doctors about how to use this and work with doctors to provide the kind of data they need on pain relief and dosing and schedule to make it really appealing, I think we could, you know, get a lot of patients on and they'll stay on for a long period of time. I think I'm bullish on the drug and I think we're gonna have a substantial market opportunity around the world. I think payers are gonna wanna pay for it because it's an outstanding drug.
You know, when you have almost every patient having reducing volume disease and we have a response rate, but even if you're not a official FDA response, almost every patient's tumors are shrinking up in a big way. You know, as you know, when you do a clinical trial. If you have the 60% response rate and the other 40% are shrinking and your waterfall plot looks like everyone's reducing, that's a pretty good finding. The doctor could say to a patient, you know, "If you take this drug, you almost certainly will have a reduction in your tumor." Whereas if you have a you know, a different clinical trial and you have a 60% response rate, but the other 40% is growing, that's a harder message. That's not what we see.
We see literally every patient having a declining tumor volume with the median being in the upper 80s%. You know, it's a very productive, relatively safe drug that I think could be taken up by the market and used widely.
Okay. Why don't we shift gears to the pipeline? You also have disclosed one ADC. We're gonna see some data this year. What can you tell us about the molecule and also the data that we'll see?
Sure. You know, the company was really put together, it was a merger two and a half years ago. A very tiny private company called MorphImmune and a very tiny public company called Immunome and then we were, you know, building. You know, took two and a half years to build where we are, I'm very proud of that. The idea was to work really hard on the next generation of ADCs and to solve a lot of the issues that were in current ADCs. I'd made quite a few ADCs on the market, perhaps more than anybody else, and so I know what the problems are with ADCs. I wanted to get to the next generation of ADCs and make them better for patients.
I also knew that that was gonna take a little time, and that's why we went out and looked at dozens of different molecules and came up with Varegacestat because I'm impatient to help patients, and I like to build companies. That's where Varegacestat came in, is to really fire us up. Now the ADCs are starting to come to the fore, and we have the ROR1 ADC in clinical trials. You know, we're intending to put out data this year, later this year. We have five others that we're manufacturing and planning for INDs, three this year, one soon, and one midyear and one late year, and then two more at least next year, and we have many more behind that, and these are novel targets for solid tumors.
I think our first two, you know, light up colon and lung cancer especially strongly. These are big market opportunities and using what I believe to be the best ADC technology out there. Now going back to ROR1. ROR1 is more of a lymphoma target with a potential upside in solid tumors. To get there, we have a diagnostic tool, and that's really important there because the expression is not ubiquitous in solid tumors where it is in liquid tumors. You don't need a diagnostic tool there, but you do in solid tumors. We're been working with a diagnostic company on that and, you know, we'll have one a little later in the year that's validated tool. It's, it exists. It's good.
On the liquid tumor front, it's expressed pretty ubiquitously on B-cell lymphoma and we're very focused on three different tumor types and that would be follicular, mantle cell, and diffuse large B. Those are the three biggest types of B-cell lymphomas. They are separate diseases. You can't just bucket them. You have to really study them, and the FDA looks at them as separate diseases. We are doing escalation. We've reported that we have objective responses at different doses during escalation. We have recently expanded the number of clinical centers and as you know, I don't like to waste time nor money, and we've expanded the number of clinical centers, so that means I certainly must like something we're seeing.
You know, when I look at ROR1, there was a molecule that was being developed by VelosBio that Merck acquired many years ago. Merck did quite a few trials in solid tumors, especially in combination with Keytruda, but didn't use a diagnostic tool, so it's hard to decide what patients to put on because it's you know, the expression of ROR1 in solid tumors is nowhere near as high as our next few ADCs looking at colon and lung and things like that, where they're expressed very strongly. I think it's important to have a diagnostic tool with ROR1. With liquid tumors, we're treating patients that have had a couple of prior therapies.
What's really important to do is figure out, you know, when you see an active drug, to figure out the dose and the schedule and maximize its activity. You know, just as an example, when you look at Adcetris, which I've developed in the past, you know, we initially started it, you know, when you look at it weekly, and certainly there's activity, but then every third week, it was much safer from a heme standpoint with very high activity and patients could stay on the drug. The next ADC was Padcev. Well, that wasn't as good giving that every third week like Adcetris. When you look at it, Adcetris has a much longer half-life. Giving it weekly, you have overlapping tox. That's why it worked better every third week. Padcev has a much shorter half-life.
We switched and we went weekly, and it worked tremendously well without overlapping tox. It's an example of two ADCs where you have to really investigate it and look at the dosing schedule to make sure you're maximizing. With ROR1, we are trying to do that now. We know it's an active drug, but you want to use the best activity that you can, and you want to expand sites. With Adcetris and with Padcev and with Tivdak, another ADC, we went and got approval in phase II. The way you get approval with a single-arm phase II is by doing your homework in phase I. When you go to the FDA and you propose approval studies, you've already done a lot of what they like to see in Project Optimus, which is what's your dosing schedule and why?
How did you maximize it for a patient? How did you maximize the efficacy and minimize toxicity and other things? To do that, you have to expand sites and you have to evaluate it. We have the challenge also of having three different diseases. It doesn't mean they all go at the same speed either. They're three different diseases and potentially three different approvals. They don't have to come at the same time. I like our progress a lot. I want to continue to see that. So far, I've been very pleased. I'm not ready to say this is 110%, you know, a commercial product tomorrow. I'm very excited, and we're spending money on it and expanding it. That's certainly a good sign. I like to be cautious on drugs.
I've developed many drugs, so I don't want to claim victory before it's ready. I think, you know, starting out with Varegacestat, which is a great drug we're submitting for approval, and going into, we call IM-1021 or the ROR1 ADC using our newest ADC technologies, which I think are the best out there because they get past different issues that other ADCs have, like resistance or, you know, not very permeable and other issues to get bystander activity. I think we have the best system that's out there.
In terms of the other ROR1, I guess DLBCL is probably the largest opportunity, but it's also the one of the more competitive ones. Where do you think, if the drug delivers what you hope it's going to deliver, where would it fit into the treatment paradigm relative to some of the other modalities in that disease?
To get a first approval, it'll have to be in patients that have, you know, 3+ prior, so 3, 4, 5 prior therapies, so you're not going into front line initially. If you can get an approval, you'll need something that's differentiating. You know, one of the reasons why I was able to get Adcetris approved in Hodgkin and T-cell lymphoma is single agent with 73% and 87% response rate respectively. That's differentiated. If we come in and the best we could do at the highest safe dose, and we come in with a 20% response rate, we're going to close the program. We're not going to keep it going because there's too many drugs for B-cell lymphoma that have 20 or 25 or so percentage response rate. It's not worth developing.
What we need to see in this heavily pretreated relapsed patients, we need to see something that's differentiated. Please don't ask me what exactly that number is. I don't have that number exactly. Differentiated could mean a lot of things. You know, it could be you have great duration, it could be a high response rate. It's so you have to look at the data in totality and consider that. I mean, so many people have asked me, you know, I would say at least 40%, maybe higher than that response rate. You know, you need to see some CRs. You need 'cause, you know, in this population, there are other drugs. You need to see a good data.
Of course, I don't want 40%. I want 50%, 60%, 70%, 80% response rate. You need to see something that's differentiated. If you see something in heavily pretreated patients with a ROR1 ADC that's differentiated, I think the FDA would rally to it. I think we could go, and if we knew the dose and the schedule and the safety profile of something, we could propose a phase II approval trial. I've done this many times. If we don't have something differentiated, that's not going to happen.
Okay. We only have a couple minutes left, but business development has been a big part of your success at Seagen, and it's been a big part of Immunome even in the early days. You've been a little bit quiet on BD recently. What can you tell us about the future?
Well, we have lots of meetings. You know, we look at a lot of different molecules to bring in. I'm glad I'm not in the investment community. It's hard to know who to invest in. I sign CDAs and I look at underlying data and wow, there's a lot of drugs that are not very good out there. You know, but I don't trade their stock, so I do CDAs and look at it. You know, I'm very picky. I've done a good job picking with Varegacestat and at Seagen with Cascadian getting to Tucatinib, which is a drug. We'll continue to look. As far as us doing partnering, there's a lot of interest in us from big companies, for sure.
We talk to a lot of big companies all the time. You know, we may have even received term sheets and other things, but what's really hard is you don't wanna partner at the wrong time. You wanna partner when you are powerful, when you have the ability to retain a big ownership in what's going forward. You know, the bigger pharmaceutical companies want you know, they want the big ownership. You know, it's the more work that we can do and the more proof of concept and the more real data, the better potential partnering can be, or we'll launch drugs ourself. You know, I mean, I'm sanguine to the fact that the vast majority of biotechs don't make it at all. They go bankrupt.
You know, and then there's only a few percent that get acquired, and then there's a fraction of a percent that become Vertex or Regeneron. I look at what we're doing, and I think, you know, my goal is to make a difference in the life of cancer patients and to take these drugs and bring them forward to approval and have approved drugs, phase III, phase II, phase II drugs. When I look at the big pharma, they are maybe not as quick as me in development, but boy, they can market and sell and distribute globally like nobody else, and they're better than biotech at that.
If I can make a great line of drugs that could get in the hands of a great pharmaceutical company to get out to patients, I could be happy with that.
All right. Thanks for spending some time with us today. Congrats on all the progress. We look forward to the data, the full data set, the desmoid program, and then the ROR1, the ADC.
Thanks.