Welcome, everyone. Thank you for joining this next session with Immunome. I'm Ami Fadia, and it's my pleasure to be hosting Max Rosett, who's the Chief Financial Officer of the company. Max, thank you for taking the time to be with us today. Maybe if I could ask you to kick us off with some opening remarks on the company and the key priorities for the year, and then we'll go from there.
Yeah, absolutely. First off, thank you for having me. It's always good to have an opportunity to talk about what we're doing at Immunome. We're expecting 2025 to be a really pivotal year for us. We are expecting, and we'll talk more about all of these things, but we are looking forward to top-line data for our phase III trial of varegacestat in the H2 of this year. We have also recently started our first phase I trial of an ADC product, our ROR1 ADC IM-1021, and we are moving towards a phase I trial for our radioligand therapy. This is really shaping up to be a transformational year for us. We are fortunate enough to be well-capitalized and have a great portfolio to execute against, and are excited to see how the rest of this year shapes up.
Okay, great. Perhaps maybe just start with an overarching question on how sort of to think about the company's portfolio. Obviously, given the history of your founders, sort of prior companies, etc., Clay Siegall, and kind of the focus in terms of the earlier stage pipeline, which is obviously ADCs, but you also have kind of a late-stage product focused on desmoid tumors. Can you kind of talk about how those two pieces sort of came about and how one should think about the company's setup and portfolio priorities?
It's a good question, right? We have a lot going on, and certainly our team has very deep expertise in ADCs. I do think the starting point when investors look at our company has to be the phase III asset. We are within six months of top line potentially for that. We've got it towards the H2 of this year. It's a great asset. It's a great market opportunity. We've learned a lot over the last year that has validated the opportunity in desmoid tumors. We really like the profile of our drug. Every way we look at our phase II data, we feel that it is superior to Ogsiveo from SpringWorks. With that kind of near-term inflection on the horizon, I think it's really important to not give inadequate enthusiasm to that asset.
I do think, though, that over the long term, we see the ADCs as a tremendous source of potential value. You mentioned our CEO, Clay, and his history with ADCs, which I think most people do not need that to be rehashed for them because it's quite well-known. I think something that's a little bit less well-appreciated is how much depth of ADC expertise we have in the company. At every stage of the development process, from discovery, biology, really understanding what leads to a great ADC target, and putting together hundreds of ADCs to test in a high-throughput fashion on into translation. We have a tech ops team that has probably put more ADCs into phase I than anyone out there, and a development team that has taken ADCs all the way from phase I through approval.
We have really been extremely fortunate to assemble an ADC team that top to bottom has deep expertise and is able to execute incredibly efficiently. A year ago, I think the story on the ADC side was very centered on Clay, and Clay is still, of course, foundational, and it is his vision that we are building against. One of the things Clay has been able to lead over the last year is building a team that really complements his vision. It is two different parts of the story. They are going to play out on different timelines. We do think that the desmoid asset is fantastic, and we are really looking forward to getting that data. At the same time, we are working very hard to move ADCs into clinical development and get to human proof of concept with those programs.
Yeah, I agree with you, given the sort of data from the desmoid tumor asset on the horizon, it is just impossible to ignore that. Maybe let's stop there. You mentioned you believe that it is sort of differentiated and competitive versus the SpringWorks drug, Ogsiveo. Can you kind of talk about where the predominant differentiation sort of comes from? Maybe after that, we can sort of talk a little bit about your phase III program.
Yeah. I'm going to take a moment and start with talking about desmoid tumors because they're a relatively rare indication. They are a serious disease, but people are not necessarily familiar with the course of that disease. That really informs how we understand this asset. Desmoid tumors, they are aggressive. They have huge impacts on quality of life. Your typical patient is going to be someone who's diagnosed in their 20s or 30s, so they'll be living with this disease for a long time. The patient population, skews female, it is typically not a fatal disease. As you think about this and think about what really matters to patients, this is not something like metastatic pancreatic cancer where you're looking to delay progression as a surrogate for overall survival.
Really, what these patients are looking for is relief of their symptoms, increased function, and essentially to get their lives back. As we have talked to patients, the things that we feel really capture what matters to them and to their physicians are different measures of response. Objective response rate. We look at that as an extremely important endpoint. What we saw in our phase II data was a 64% objective response rate in the intent to treat population compared to 41% for SpringWorks in their phase III study that they used for FDA submission. If you look at tumor volume reduction, which is sort of another way of measuring the same thing, we saw an 88% median reduction in tumor volume compared to a 59% reduction for SpringWorks.
Overall, I should emphasize, we believe these patient populations in these two studies were very similar, although obviously it's always challenging to compare across studies. That tumor volume reduction, if you think about having a softball-sized tumor in your neck, a 58% volume reduction, 59% volume reduction, that's going to take it down to being the size of a baseball. An 88% volume reduction, that's going to take it from a softball to a golf ball. If you think about the benefit that that actually delivers to a patient who has pain, they have the cosmetic impact of having a lump, they have potentially some loss of range of motion and function. You really want to do everything you can to alleviate the symptoms.
As we looked at the phase II data for varegacestat when we were diligencing this asset about a year and a half ago, we just saw differentiation every way we sliced the data. It looks fantastic. People say, "Hey, that 64% response rate, that's in 14 patients." It was 14 patients at the phase III dose of 1.2 mgs daily. If you look at all 42 patients, two-thirds of which were on what we view as suboptimal doses, the response rate combined across all of those groups is still 54%, again, compared to 41%. We are incredibly excited that when you look at the things that really matter to patients, sort of no matter how you cut the data, you see really fantastic efficacy. We are excited to see how that translates in phase III.
Sorry. Yeah, maybe if you could sort of elaborate on how these patients are going to get treated in terms of the duration of treatment. Is this sort of a chronic treatment, or is it treatment to the point where you achieve a certain response, and maybe there's some sort of a treatment holiday given to patients?
Yeah, I think that given the chronic nature of this disease, we expect patients to spend a lot of time on drug. One data point that I can give there is in the last data cut that we shared from the phase II portion of this study. The median time on treatment was, I believe, 20 months, and that was still with the majority of patients remaining on drug, right? You are seeing multi-year treatment durations because of the benefit that these patients receive. I think that over the very long term, we are still learning what the four or five-year course of treatment looks like. It absolutely could be the case that this is something where patients take drug holidays because maybe there is some toxicity that is bothering them, and then they come back.
As we go to launch our drug with SpringWorks already on the market, we can see that being favorable, right? If patients are going on drug holiday, maybe they take the opportunity to try something new when they come back to treatment. We think that there's still a lot to learn about what the long-term course of treatment looks like, but we're incredibly optimistic that over time, it adds up to a tremendous amount of time on drug because these tumors really are a chronic condition.
Can you talk about your phase III trial that's ongoing? Are there any differences in the endpoints, the type of patients that you're studying there, and maybe also compare with how patients are sort of tracked and evaluated by physicians in the real-world setting?
Yeah. Our phase III study, which is called RING SIDE Part B, fully enrolled in February of last year. It has been fully enrolled for 14 months at this point. That study has a primary endpoint of progression-free survival, and I'll sort of take a moment to talk about that. It is an event-driven study, and there is an important point here, which is we have been guided to top-line data in the H2 of the year. We've kept that guidance for a year, and we feel good about that guidance. Event-driven studies tend to be a little bit unpredictable.
Now, what I will say, one thing that gives us reassurance about that guidance and makes us feel better is that with event-driven studies, if you get to a point where you feel that the data is mature and you have not reached the originally targeted number of events, there is some discretion about when you choose to unblind them. It is something where you would want to engage with the FDA and make sure that the data set is mature. SpringWorks originally intended to get to 51 events for their study and then ultimately went to the FDA with 49 events. As far as the primary endpoint goes for that study, it is the hazard ratio for progression-free survival. We view that as a regulatory endpoint. We think that it is an important way to characterize the drug.
As I've already said, we feel that objective response rate and tumor volume reduction more directly capture what patients are looking for. There is a slight difference between how we are tracking progression-free survival compared to SpringWorks. Our endpoint is purely radiographic progression, whereas the SpringWorks endpoint could be either radiographic progression or clinical progression. What does that mean? I think ultimately, we do not expect it to lead to a big difference in terms of the hazard ratio. In fact, we will present the composite endpoint as a sensitivity analysis, just as SpringWorks presented the radiographic-only endpoint as a sensitivity analysis. The one place you could see it show up is that since we are only counting one kind of progression and SpringWorks was counting two, the median progression-free survival in our placebo arm could be slightly longer.
That's not necessarily going to reflect differences in patient population. It's just going to reflect a subtle difference in how we are defining progression-free survival.
Could you sort of break that down a little bit around what are the two ways in which you're sort of evaluating the progression-free survival and why would the placebo arm end up showing a longer PFS? Is it that it just takes longer for that to show up in a radiographic?
Yeah. If you think about radiographic progression, right, what happens is every, I believe, 12 weeks, a patient comes in and gets scanned. If the tumor has grown a certain amount, 20%, that is treated as a progression event. That is radiographic progression. It is purely imaging-based. That is solely how we are defining progression-free survival in our study. In the SpringWorks study, they counted radiographic events, and about 80% of their events ended up being radiographic events. They also counted clinical events. That is a patient comes in and says, "Hey, my tumor's causing me more pain. It's getting worse. I think it's time for me to come off this study," or the physician saying to the patient, "I think it's time for you to come off this study." You can imagine that these two things frequently happen in parallel.
Frequently, if the patient perceives that the tumor is getting worse, it is also going to correspond with an increase in the diameter of the tumor and with radiographic progression. Logically, if you have two different ways that you can trigger a progression event and then compare that to our study where there is only one way to trigger a progression event, you can see why that would lead, even in very similar patient populations, to subtle differences in the reported median progression-free survival. On the SpringWorks study, with the more expansive definition of progression-free survival, their placebo patients had a median progression-free survival of 15 months. With the more restrictive definition of progression-free survival, which they had as a sensitivity analysis on that study, the median was not reached.
The only reason we're making a big deal out of this, we don't think it changes what kind of hazard ratio we will report. We don't think that it changes. It has no impact on all of these secondary endpoints of objective response rate or tumor volume or patient-reported outcomes. The only reason we're making a difference is we don't want people to sort of see our median progression-free survival be not reached in the placebo arm or be somewhat longer than 15 months and say, "Oh, this is a different patient population." The eligibility criteria for the two trials are very similar. Both of them, we're looking at patients who've seen 20% increases in tumor volume over 10 months or, sorry, over 12 months. That's the definition of progressing desmoid tumor patients. They're being conducted at many of the same sites.
Overall, we feel really confident that the patient populations are going to be similar, and we just don't want anyone surprised by a slightly different definition of median progression-free survival.
That makes sense. Just one other final point around the timing of the readout. You've got it to H2 of this year. At this point, just based on the event rate, I'm presuming that you still expect it to be in the H2 of the year. You mentioned something about sort of the potential to go to the FDA with an earlier data cut. Can you clarify what that means and what would trigger a consideration of doing that?
Yeah. As I said, we feel really, really good about our guidance for the H2 of the year. We first put out that guidance in May of last year. As we've tracked the study since then, we've continued to feel that the appropriate guidance is H2 of this year for top-line data. One thing that can happen with event-driven studies is you don't know when the events are going to come in. That's why we didn't guide to a quarter. We guided to a half of the year. Looking at the SpringWorks experience, they got to a point where the event rate, they sort of said, "Hey, this is not going to get to our originally targeted number of events." Based on that, we feel like we should, we think we have a really robust data set as it is.
We think it's a mature data set. We think that it captures everything that's needed. Ultimately, they were correct. They had targeted 51 events. They got to 49. They didn't know how long it would take to get incremental events. They went to the FDA. I presume that they went to the FDA beforehand, although I can't directly speak to that. They were able to stop it at 49 events and still have a good hazard ratio, still have really robust secondary endpoints.
Okay, that's great. Now, let's just sort of think about the commercial market opportunity. Obviously, SpringWorks has done really well so far. Maybe help us think about the market positioning for your product and where do you see the patients coming from and kind of what is your view of the potential peak market opportunity?
Yeah. We are hoping that we will have phase III data that positions this as a clearly superior drug, right? I would go back to saying, "Do you want to shrink from a softball to a baseball or a softball to a golf ball?" Right? We want to be bringing patients something that is a fundamentally different product in terms of the response they can expect, both measured as magnitude of response, but also probability of having some degree of tumor volume reduction. SpringWorks, I think, has done a good job of validating that this market is real and that it is perhaps bigger than some skeptics anticipated. Their Q4 sales, they were at a run rate of close to a quarter of a billion dollars annually one year after launching the drug. We think that it is a big market.
We think that we can be the best drug in that market. We have not given guidance to peak sales. We will have to see exactly what our phase III data looks like before we feel like it is appropriate, before we feel like it is appropriate to commit to a number. Overall, we think that it is a very, very big market. We also think that it could be commercialized pretty effectively, cost-effectively. We brought in a Head of Commercial last fall, Roee Shahar, who was formerly at Pfizer. He had four brands at Pfizer. I think he is very comfortable with commercializing a drug like this.
Desmoid tumors are treated at a relatively small number of centers in the US, so it is not a huge sales force. It is a patient community. As I mentioned, these are young adult women. There is a lot of sort of patient advocacy groups online. There are a lot of ways to have word spread within the community. Overall, we feel like it is a very tractable commercialization. Given that we have a fantastic Head of Commercial, given that it is a relatively small effort to commercialize, we are very ready to commercialize this drug ourselves. I think sometimes investors assume, like, "Hey, we're going to get this to top line, get it to approval, and then flip it to someone else." That is absolutely not our plan. For the right offer, of course, we would consider it. Our plan A is to move forward this drug into commercialization.
Can you give us a rough number of how many centers of treatment are there in the US? Is there an estimate out there for it?
I believe it's about 100. Very tractable. And I.
Go ahead.
I'll emphasize, many of the KOLs are participating in our study, right? This is not a huge community. We have a good number of sites on our study. We feel like many physicians already appreciate what our drug offers. We've had, these are anecdotes. The plural of anecdote is not data. We've had physicians come up to us and we'll say things, "Well, if our drug turns out to be better than the SpringWorks molecule," and they cut us off and say, "Oh, it's better." They've treated maybe four patients or however many they have on their site. They don't have the full data set. Nonetheless, we take that as encouraging.
From a commercialization standpoint, is the focus going to be sort of to build awareness that there are treatments available and bring in more patients into the physician's offices, or is it really tapping into the market that has not yet been tapped into by SpringWorks? Thirdly, do you anticipate switching from the SpringWorks product to yours given the potential for a superior clinical profile?
Those are all really fair questions and I think are going to be hard to answer in advance of actually having the phase III data that fully characterizes the product. We do think if you sort of imagine the course of treatment for someone who was diagnosed with this disease 15 years ago, it's like, "Okay, maybe they got surgery." It turns out that frequently the trauma of surgery leads to it growing back. You have this invasive surgery, you sort of momentarily have some relief, and then the tumor comes back. Maybe you tried off-label chemotherapy or an off-label TKI. You had toxicity. It didn't really work.
I think anecdotally what we've heard is that as patients actually have something that really works, that can really alleviate their pain, that can really improve their quality of life, they are coming out of the woodwork. We do think that there's a real opportunity to sort of grow the pool of patients. Beyond that, I think it's hard to talk in too much detail about commercial plans for a drug that has not yet reached top-line data.
That makes sense. Okay. I want to shift gears to the ADC platform. You talked a little bit about the really sort of deep set of capabilities that the company has with all the employees that had extensive experience at Seagen and other companies from working on ADCs. As you guys have picked the ADCs that you are moving forward, is there sort of a formula for really screening the ADCs, or is it really banking on the experience of all the sort of collective at the company to really look through everything and identify, "Okay, what makes sense? What does not make sense?
I think it's a little bit of both, right? There's certain things you need to have, right? One of the things we're looking for, we want very clear efficacy at low doses, and we want tolerability at very high doses preclinically. That's something we consistently see. I think that where the experience comes in is the ability to really understand what makes a good ADC target. If you look at the ADC landscape, you have 55% of clinical programs going after 10 targets. Don't get me wrong, HER2 is a fantastic target. That is why there are many, many approved drugs, ADC and otherwise, targeting HER2. Nonetheless, we have more than 40 ADC programs going after HER2, right? We just don't feel like there is value to patients or to companies or to investors to adding an incremental HER2 ADC.
We think the starting point is doing the hard work of going out and identifying targets where the biology of the target, the expression of the target, the indications that's relevant to all really work and present an opportunity for an ADC that is not going to be yet another TROP2 , but is going to be something that can really make a difference to patients. Having the team that can do that target validation work and get real conviction because it's kind of scary to go after new targets, right? HER2 is sort of a no one's going to come back to you and say, "Oh, HER2, that was a dumb target to go after." Doing the work preclinically to get comfortable with novel targets is really important. We're really excited about the profiles of the targets we've been able to identify.
You have to pair that with great technology. I think that it frequently gets framed as like, "Well, is it about targets or is it about technology?" You need both. The second piece of the puzzle for us is our platform. We have a lot of stuff in our toolbox, some of which we're not ready to talk about, but our IM-1021 program and then our three named programs coming after that, 1617, 1335, and 1340. They use the HC74 payload. We really, really like that payload. We think that it is, there may be a better ADC platform out there, but we don't know what it is. We haven't come across it. That is a TOPO1 inhibitor. TOPO1s are a great class. They have, obviously, you don't need me to talk about the impact that HER2 has had.
We really like the broad therapeutic index where you can treat patients at fairly high doses and see nice activity. There are a couple of things about HC74 that we think make it substantially better to DXd that payload in HER2. It seems to escape some of the common pathways that cancer cells use to develop chemo resistance. Things like efflux, where cancer cells pump the cytotoxin out of the cell, our drug seems to avoid those pathways. We have data that shows that we are resistant to that and that we maintain efficacy in chemo resistant cell lines. Another thing that people do not talk a lot about is permeability, right? If you think about a mouse model, you have this super homogenous tumor where everything in the tumor expresses the target at a high level.
Patient tumors are much more complex, much more heterogeneity. One of the things that you want is bystander effect, where an ADC goes into a cell that expresses the target at a high level, and the linker payload gets cleaved and the cytotoxic is released. Then it can diffuse into nearby cells that do not express the target at the same level and kill those too, right? In our mind, it is sort of so easy to get focused on potency as the end goal, right? Or something like that.
We think that there are all of these more, one of the things that our team has learned over decades of experience is that there are all of these more subtle things that actually have a huge impact on what you see in terms of results that just are not as obvious to talk about as something like, "Hey, we want the most potent payload we can possibly get.
Okay. A lot of the assets in your portfolio you've sort of acquired through business development. Help me understand sort of the trade-offs between sort of taking this wealth of knowledge and building something from scratch yourself versus bringing in something externally. Also in this sort of competitive environment with a lot of companies looking to build their ADC platform, how do you compete in that to really sort of kind of in terms of a financially sort of sound way, bring in assets through business development?
We were able to really jumpstart our pipeline with some great business development deals last year. Varegacestat, we were able to acquire that for very little money upfront. We think it's a fantastic asset, right? Business development, it's incredibly, it's fast, right? You can build a pipeline quickly. I think we're at a point where if we came across another varegacestat, an asset with great phase II data, a phase III that's already underway that we can buy cheap, like, "Yes, we will sign up for that again." As we've built our discovery efforts, I think there's a lot of upside to having controlled everything that's been done with the molecule, ensuring that on the ADC side, you picked the antibody you want, the linker you want, the payload you want, the clinical development strategy that you want.
There's a lot of value that can be added by making sure that you get every single thing right. We are always interested if we come across good assets at a great price. We have built a very good discovery team, certainly a very cost-effective way to expand your pipeline. This is not a wasteful effort in the sense that it is a very disciplined discovery team that is adding to our pipeline for much, much less than if we were to go out and buy assets from someone else.
Yeah. Okay. Maybe if you could talk as much as you can share on kind of your ROR1 asset and also the radioligand. What gets you excited about those two assets? And perhaps just lay out kind of how you see them moving forward in the next 12 to 18 months.
Yeah. The ROR1, we started that phase I in the Q1. We're incredibly excited about that asset for a whole bunch of reasons. ROR1 is a super interesting target in that it has great B-cell lymphoma expression. It also has solid tumor expression. We've shared preclinical data showing really nice efficacy in both of those settings. I'll be brief here just in the interest of time. On the lymphoma side, the Merck molecule that they acquired from Velos Bio, that I think has demonstrated the potential of ROR1 as a target in lymphoma. They're now moving it into a phase III study. I do think that you see real limitations on the toxicity side there. They were only able to bring a dose of 1.75 mg per kg into the phase III study in combination with R-CHOP for frontline DLBCL.
By contrast, we feel like we have superior potency. We have a DAR of 8 compared to a DAR of 4 for that molecule, but also much, much better tolerability. We are starting our phase I study, or we started our phase I study for that at a dose of 2 mg per kg, which is higher than the dose that Merck is taking into phase III. We will be doing dose escalation from there. We are doing dose escalation both in lymphoma and in solid tumors in parallel. We will see what the dose is and then add expansion cohorts as is appropriate. We are not guiding to sort of a particular time when we will have data to share. I feel pretty good saying that we will have data for that program this year. Does not necessarily mean that everyone will have data.
We want to be thoughtful about sort of the right venue, right conference for sharing data when we do have it. I think that program has real differentiation. It has a target that has been somewhat validated, and it has a path to move forward quickly. On the radioligand, go ahead.
Sorry, can I just have one very quick question there? What are the doses that you look to test as you go up the escalation?
I can't recall if we have shared every dose level, but it is a dose escalation study.
Sure. Okay. Thank you.
On 3050, which is our FAP radioligand therapy, FAP is a target that is expressed in a huge number of solid tumors. It's in 75% of solid tumors. It is a little bit of an unusual target in that it is expressed on the fibroblasts rather than on the tumor cells themselves. That actually makes it a really, really good fit for a radioligand therapy because radioligand therapies, and especially beta emitters, which is what we're using, we're using 177 Lu , which is a beta emitter. When they decay, they kill cells in a radius around. They have a path length that can be five cell diameters. If you're targeting the fibroblasts, what we believe mechanistically is really nice about using a radiotherapy is that you have this really great bystander effect driven by the mechanism.
It just feels like this perfect match between the biology of this ubiquitously expressed target and the advantages of a radioligand therapy. I think that's the reason that we've taken on the challenge and have been able to solve the logistical challenges of bringing forward a radiotherapy. We submitted the IND for that in the Q1. It's going to take a little bit longer to get that phase I started. We think that will be the H2 of this year, which was a longer interval than we saw for the ADC just given the challenges of our radiotherapy.
Okay. Perhaps in the minute or so that we have left, maybe if you could sort of close by reminding us about the company's cash position, how sort of it might fund through the ongoing phase III and these other two programs we just talked about. Just broadly, how are you guys thinking about further additional business development from here on? Should we expect y'all to continue to add to kind of that early stage pipeline, or can we also expect you to sort of do something more substantial, like you mentioned, something with the phase II completed, ongoing phase III type of an asset?
Yeah. As far as cash, we finished the year with $217 million. That's what we've had in our 10-K. We were fortunate enough to raise $172.5 million gross in January. I think that in this environment, feeling well capitalized with runway into 2027 is pretty fundamental. Having the cash to advance a really high-quality pipeline is a great position to be in, even with the recent turmoil. As far as the pipeline, we have a lot of really great early stage assets. I think our bar for adding something early stage would be extremely high. I'm not going to categorically say never because it's always context. It's always about what's the data, what's the cost, etc. I mean, I feel very comfortable. Prior to doing the varegacestat deal and prior to doing the deal for IM-1021, I think we felt a need to do deals.
We do not feel a need to do deals right now. It is a great market to go shopping in, but we have got a fantastic pipeline. I think that if we spend the next 6, 12, 18 months just advancing what we have, people will be really happy with what we accomplish.
Okay. Max, I think we've run out of time, but this was a great discussion. Thank you so much for sharing all of that with us. Thank you to all our listeners for joining.
Yeah. Thank you.