Great. Good morning everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen's 46th Annual Healthcare Conference. For our next session, I'm very excited to have a hybrid presentation and fireside style chat, Q&A, got through that, with Immunome. It's my pleasure to introduce Max Rosett, the CFO of Immunome. Max, privileged to have you here. Thanks for joining me. I'll hand it over to you for the presentation.
Thank you so much, Tyler. Privileged to be here talking about Immunome today. I will be making forward-looking statements. Please see our disclosures for more information. What we're building with Immunome is a company focused on targeted oncology, and highly differentiated products that are either first in class or best in class. The most advanced of these is varegacestat, a phase III asset that had positive top-line data in December, and that we're now preparing for NDA submission in desmoid tumors. We also have a large pipeline of highly differentiated ADCs, the first of which is in phase I, and three more of which will have INDs over the course of this year, early, middle, and late. We also have a radiotherapy with an active IND that should be dosing the first patient shortly.
Our intention with Immunome has always been to build a big pipeline of products that can make a real difference in the lives of cancer patients, and we are well on our way to doing that. Today, I'll start off by talking about varegacestat. Varegacestat is an oral gamma secretase inhibitor that can be given once daily for the treatment of desmoid tumors. In December, we were able to report top-line data, which is summarized here. I think it is fair to say that you could spend an entire career in biotech without ever seeing data like this. In the RINGSIDE study, we demonstrated that varegacestat reduces the risk of progression by 84% with a hazard ratio of 0.16. It achieved a 56% objective response rate and an 83% median best tumor volume reduction.
All of this was achieved, as I mentioned, with once-daily dosing. The drug was generally well-tolerated with a manageable safety profile. We are on track for the second quarter 2026 NDA submission timeline that we guided to at top line and are looking forward to getting that done. We do not feel that there are any sort of specific challenges or roadblocks between here and that submission. It's just a question of completing the large amount of work that goes into any NDA submission. For those of you who are not familiar with desmoid tumors, these are rare tumors that are painful, debilitating. In extreme cases can be life-threatening. Typically, quality of life is the biggest concern with desmoid tumor treatment. Surgery is no longer viewed as appropriate for most of these patients.
There's a high rate of recurrence, especially after surgery. At present, there is only one approved systemic therapy for desmoid tumors. That is nirogacestat, which was approved in late 2023. Varegacestat pursues the same target as nirogacestat. They're both a gamma secretase inhibitor. The key differentiation for varegacestat is that it has a substantially better PK profile with a half-life that is nearly twice as long, supports once daily dosing. The phase III study, the primary endpoint was progression-free survival. There were additional secondary and exploratory endpoints. At top line, we released the data that I went through the summary of earlier. We will be presenting the full data set at an appropriate major medical conference later this year.
As you can see, the Kaplan-Meier curves separated early and only grew further apart over the course of the trial, showing a significant reduction in the probability of progression for these patients. In addition to delaying progression, we saw substantial tumor shrinkage. On the left-hand side, you have best response per RECIST, which you can think of as a linear measurement, with 56% of patients achieving confirmed objective responses. On the right-hand side, we have the three-dimensional volumetric measurement per MRI of tumor reduction. The median patient in our phase III who was treated with varegacestat saw an 83% volume reduction. That is a tremendous potential patient benefit. We also disclosed that we achieved statistical significance on all of our secondary endpoints, including a PRO endpoint related to pain. Pain is a big consideration for these patients.
It's a big part of what doctors are hoping to treat for. We were very pleased to see a substantial benefit on that endpoint as well. Overall, varegacestat was generally well-tolerated with a manageable safety profile that we view as consistent with the class. In general, patients feel that they get tremendous benefit from this drug and that the side effects are manageable, given the magnitude of the benefit. We view varegacestat as the latest step in the progress of systemic treatments for desmoid tumors. Prior to nirogacestat, there were no approved treatments. Nirogacestat marked a substantial step forward for desmoid tumor treatment.
We were very pleased to deliver a drug that achieved a 56% objective response rate in a phase III setting, and are looking forward to submitting the NDA and preparing to launch this drug. Our goal is going to be to expand the desmoid tumor market. At present, we believe there are 10,000-11,000 actively managed patients for desmoid tumors in the U.S., only about 10% of which are currently on gamma secretase inhibitors. In addition to winning the existing gamma secretase inhibitor market, our goal will be to expand that market substantially. We believe that the once-daily nature of our drug will make it easier for patients to stay on long-term, compared to twice-daily dosing for niraparib, and that superior patient adherence will lead to excellent real-world results.
As I mentioned, we will be submitting this NDA in the second quarter of 2026 and are prepared to launch this drug ourselves upon approval. Next, I will turn to the ADC portion of our portfolio. My colleagues at Immunome bring deep expertise in ADCs, with many drugs designed, approved and launched over the years. We've now had approved ADCs for more than 25 years, with the first one going all the way back to 2000. Over that period, it's become clear that there are just certain limitations that determine how fully ADCs can be used. Things like having a limited therapeutic window or for drugs that are successful, cancer developing resistance to the drug or poor bystander effect as limiting factors for ADCs.
Our goal has been to develop a technology that we can pair with appropriate targets that overcomes these limitations. We believe we have that in HC74, our proprietary ADC payload, which I'll discuss in a little bit more detail. Our first ADC is IM-1021, which is a ROR1-targeted ADC that is currently in dose escalation. ROR1 is a target that is expressed in both liquid and solid tumors. Our focus at present is on lymphoma. We are also developing a companion diagnostic that will let us select patients for usage in solid tumors. We started dose escalation last year, and it is ongoing, and we expect to share a dataset later this year. We were very pleased with the preclinical package for 1021.
MK-2140, also known as zilovertamab vedotin, is another ROR1 ADC that is currently in a frontline phase III study, being compared to R-CHOP, or R-CHOP plus 2140 in comparison to R-CHOP. You can see here that when dosed equally, we have superior efficacy preclinically. However, that dosed equally is a very important point. Merck- 2140 was only able to go into phase III with a dose of 1.75 mgs/ kg due to the narrow therapeutic window that is frequently associated with drugs in that class. By comparison, IM-1021 was able to start dose escalation at a dose of 2 mgs/ kg.
We believe that the Topo1 payload and the properties of the ADC platform that we've used with 1021 will support a broad therapeutic window that will ultimately let patients stay on drug, achieve higher doses, and ultimately achieve superior therapeutic benefit. I would like to briefly touch on some of the properties of HC-74 that I've alluded to. One key limiter of existing ADC technologies is their sensitivity to resistance pathways mediated by efflux. What you can see here on the left is that as cancer cells are exposed to cytotoxins, efflux transport or pathways associated with efflux transporters tend to be upregulated, and that literally just pumps out the cytotoxic payload before it can kill the cancer cell.
This has been in addition to being quite intuitive why that would have an impact, there is clinical data that shows the impact of this. If you look at the expression of efflux transporters in patients and segment those who are below average versus those who are above average, those with below-average expression achieve an objective response rate of 47% when treated with a TOP1 payload, compared to 17% for those with above-average expression, so nearly a three-fold difference. There is good clinical data highlighting the relevance of efflux transporters to limiting the efficacy of TOP1 ADCs. What we have shown is that in addition to demonstrating through assays that HC74 is not subject to these transporters, when we actually look at HC74 ADCs in models that upregulate these transporters, we continue to see very nice efficacy.
HC74 also has enhanced bystander activity, which allows it to achieve greater bystander effect, which is a key consideration in the highly heterogeneous tumors that you see in real-world patients. A standard question that we get is if you believe you have a best-in-class ADC technology, aren't you going to stick it on trastuzumab and give us another best-in-class HER2 ADC? Our perspective is that at last count, the world has 36 clinical-stage HER2 ADCs, and it is not the best use of our resources to provide the world with a 37th HER2 ADC. Although we love our technology and we believe it's highly differentiated, we think it also needs to be paired with differentiated targets. That brings me to the rest of this year.
As I mentioned in my introduction, we will be bringing three ADCs into the clinic or be bringing three ADCs to IND over the course of this year, early, middle, and late 2026. All three of these ADCs use our highly differentiated HC74 technology. All three have undisclosed targets. We have done a lot of work to identify targets that have fantastic preclinical profiles, and really compelling target biology, but also are not currently being pursued by any other ADC programs that we are aware of. Those programs will be going into the clinic fairly soon. We are viewing 2026 as the year where the ADC portion of the Immunome story becomes increasingly real and relevant both to patients and investors. I want to assure you, though, that 2026 is just a start.
We have numerous additional ADC programs in discovery and preclinical development, with the intention being additional INDs in 2027 and beyond. I will briefly mention that we have IM-3050, which is a FAP-targeted radiotherapy with an active IND. We have been working to secure the radiotracer diagnostic that will be necessary to diagnose the first patient and believe that we'll complete that shortly and diagnose our first patient in the near future. That will be another thing to look for over the course of 2026. We believe that Immunome is just getting started. Since the very beginning, we have been committed to building a portfolio of breakthrough oncology therapies. Varegacestat was our first clinical success. We are incredibly optimistic that we will be bringing forward others in the near future. Thank you.
Great. Thank you very much for that presentation, Max. Naturally we'll start with varegacestat given the near-term filing you mentioned for the Q2 NDA submission. There's no specific items holding it up or gating items other than the, you know, all the work you need to do for the actual filing. Curious to get your latest thoughts on the manufacturing front. My understanding was there was some work to do following the incredibly favorable transaction from Ayala. Where are you at in manufacturing? Assuming you submit the NDA in Q2 and get approved either on a priority or standard review timeline, will you guys be ready on the manufacturing front, and what's your current supply capacity?
Yeah. We will 100% be ready on the manufacturing side. What Tyler's referring to is when we brought this asset in in early 2024, if you listened very carefully to what we were saying, we were hinting, "Hey, you know, the phase III is fully enrolled. It's going well, but the manufacturing's a little bit of a mess, and we don't know if that will be ready in time for the NDA submission." We cleaned that up. Our tech ops team is fantastic. They went in, sort of evaluated everything. You know, there was a lot of work that needed to be done, but that work is all done. We no longer view manufacturing as sort of a particular risk for this program. We will have ample capacity for commercial supply to launch this drug around the globe. We're incredibly happy with the work that our tech ops team was able to do.
That's great. With OGSIVEO and varegacestat, they set a pretty high bar with their data. You guys, you know, clearly exceeded that bar as you showed in the presentation, a very impressive data all around. Again, one would expect that you guys get significant uptake, not just in general, but from patients on OGSIVEO potentially. Can you just elaborate on the market, right? You, you mentioned 10% and there's ways to grow it, but have you heard anything about the OGSIVEO launch and why it? You know, some people think it's kind of like plateaued and maybe the market's a bit smaller than they previously anticipated. Curious just to hear you elaborate on the market and where you guys think it can grow to.
Yeah. We think there's tremendous on top potential here, right? 10,000 patients that are actively managed in the U.S. with the net pricing that OGSIVEO sees. If you can get to 3,000 patients, that would be a billion-dollar a year drug. The question is what's going on with OGSIVEO? Because for a while their launch seemed to be going very well, and now there seems to be this perception that it's stalled. I'm not gonna dwell on the fact that transactions are incredibly disruptive. I think it's easy to overlook the fact that SpringWorks Therapeutics was acquired, and not only were they acquired, but it was sort of in a highly visible way with articles in The Wall Street Journal. That just does not lead to great execution on the launch of a drug.
I don't think it's worth dwelling on that other than just noting it. What I would say is that OGSIVEO did a good job of taking the market of patients who were going to get systemic treatment anyway. If you look at, if you look at patients, some were getting, you know, sorafenib or off-label chemotherapy or things like that to treat these tumors, and that has largely been displaced by Niro. The question is: how can you start displacing things other than the small slice who were already getting systemic treatment? I think that if you tell a patient, like, "Hey, first, surgery is not actually indicated, but also our pill can achieve 83% volume reduction without the need for surgery," that's a pretty compelling message.
The question is going to be: how do you expand the market beyond the patients who were going to get systemic treatment anyway? The other thing I'll note is that, kind of what's happened with Niro is they're continuing to get new prescriptions, but patients are going off drug. Niro is a twice-daily drug. You hear that, and you think, "Oh, this is a question about convenience." What we hear anecdotally is that patients start taking it once a day. It does not actually have the profile to support once-daily dosing. If they did, that's what the label would be. The flow is sort of, hey, I'm taking this once a day for one reason or another, for convenience.
I'm seeing efficacy in the real world that is maybe even lower than the 41% that was reported in their clinical trial. It's like, well, this drug isn't working for me, 'cause I'm not taking it correctly, so I'm going off of it. I think one of our real focus areas is going to be how do you keep patients on drug? Patients stay on drugs that are working on them. They stay on drugs where they feel like their tumors, you know, their pain's going away, their functionality is coming back, their quality of life is getting better. In addition to growing the market, there's a big question about how do you keep patients on drug, and a lot of that comes down to making sure they're getting sufficient benefit.
Yep. On that topic, what does the clinical data suggest that duration of therapy should be with varegacestat?
Yeah. We haven't, we haven't disclosed those details from top line, but I think if you look at the latest data cut, that we shared for phase II, it was something like a median time on treatment of 22 months. This is something where you absolutely can see patients staying on the drug for years and years. One of the things that we really like, and again, this is sort of referencing phase II data 'cause we haven't shared the full details from phase III, is that even 12 or 18 months in, you still see tumors shrinking. Patients get benefit quickly. By the first scan, you're already seeing responses. Anecdotally, they get pain relief very quickly. The benefit seems to be cumulative, so those responses get deeper and deeper and deeper.
You know, maybe after two scans or 24 weeks, you've seen a 50% volume reduction, but if you stay on it for another 12 months, you'll get to that 80% or 85% volume reduction. We think that there's the potential for very, very extended treatment and a key point is none of the toxicities appear to be cumulative. Typically you take the drug, whatever toxicities you're gonna see, you see them pretty quickly. You figure out how to manage those, and then there's no reason that you can't stay on the drug long term.
Okay. From a commercial and I guess financial standpoint as well, how are you thinking about right-sizing the launch? How many sales reps or how many people in the commercial infrastructure might you need, and how are you thinking about spend?
Yeah. Overall, this is gonna be a very cost-effective launch. We're still doing the work to really define our sales territories. You don't wanna do that until you know the profile of your drug, so that's ongoing now. What I can tell you is that OGSIVEO had something like 32 or 35 sales reps and something in that ballpark feels about right. It's going to be a very cost-effective launch in the U.S. I think that given the size of the opportunity, investing appropriately, is something that will be sort of easy to do. It's not going to be some kind of dramatic financial strain. What you get, you know, you invest in medical affairs, you invest in helping doctors use this drug to provide the most benefit that's possible to patients. I think you can see a very different trajectory than what SpringWorks ultimately accomplished.
Okay. Great. If that's the case, obviously it's an incredible deal given how much you guys had to pay up front.
$50 million up front. Yes.
Pretty impressive. All right, we'll move to a favorite topic in the core of Immunome, ADCs. On 1021 ROR1 ADC, you gave a nice overview over there as to why you guys are excited about it. But maybe you could elaborate just on the design differences or the differences versus Merck's zilovertamab and why you think it could be superior to what Merck has shown historically.
Yeah. Absolutely. Great question. You know, there's sort of two ways you can go about constructing an ADC. One is you sort of grab the first antibody you come across, grab the first payload you come across, use some duct tape to put them together. At, at risk of being a little bit unfair, that's kind of how I would describe ZV. It was originally a research antibody that had been brought into the clinic as a monoclonal. It was not sort of optimized for usage as an ADC. What our approach is always going to be is, you know, you do the target biology, and but then you optimize every step of the chain.
You pick the right target, you pick an antibody that is selected for ADC-specific properties like internalization rate, you use the right linker, the right payload. We really like the antibody we have. We have our HC74 payload on there, which is a Topo1. I've already touched a little bit on the difference in therapeutic window. In some ways, you know, we look at the ZV data, and when they dosed up to 2.5 mgs/ kg, they were seeing fairly good activity in some of these B-cell lymphomas, but they just couldn't dose there. It was too toxic. At 2.5 mgs/ kg, they had 80% grade 3 or grade 4 toxicities.
In some ways, when you have a competitor who has shown a lot of activity but just has too much toxicity at the relevant dose levels, and you bring forward something where it's like, "Hey, the Topo1 class is well understood, we expect to have a wider therapeutic window, we expect to be able to dose higher," that gives you a lot of confidence in what you'll see in B-cell lymphoma.
Great. Think I'm gonna use duct tape in one of our notes.
Okay.
I like that. You've noted that you've observed responses with IM-1021. As we think about the upcoming data disclosure, what would constitute a win in terms of response rate that would give you all confidence to move forward with this program?
That's a good question, but a hard one to answer. We're looking at this in multiple subs of multiple different subtypes of B-cell lymphoma. You know, we're looking at it in patients who have varying degrees of pretreatment, so giving you a number right this moment is a little bit hard. Certainly, you know, if we come back with a 30% objective response rate, I think probably the next sentence is, "We're shutting down the program." We want something higher than that. I think our goal when we share a data set is to answer a lot of questions at once.
You know, we have the luxury of being a near commercial stage company with varegacestat, so rather than having to sort of drip out one patient of data at a time on the phase I, we want to figure out dosing, we want to figure out exactly which subtypes of B-cell lymphoma we want to go after, and provide a data set that really gives people a picture of what we're going to be doing with this drug.
That's great. How about solid tumors? Do you think that is a realistic opportunity for IM-1021?
With solid tumors, there absolutely is ROR1 expression, but it seems to be a little bit of a bimodal thing, where there's some patients who express them, some who don't. We've been developing a companion diagnostic to use for patient selection. And I think that will be the key to unlocking solid tumors. You know, you pair a great ADC that's optimally designed with selecting the right patients, and I think there's a real chance in solid tumors. We've always positioned that as sort of a less de-risked companion to lymphoma with a very large opportunity if it does indeed work there. Other thing I would say is all three INDs that we're filing this year are solid tumors. IM-1617, that preclinical solid tumor data package is just phenomenal.
It's always challenging to go from something that works in mice to something that works in humans, but we are incredibly excited. I work with some of the most experienced ADC developers in the industry, and I think the consensus is that this is as good a preclinical package as they've ever seen.
For the 3 solid tumor ADC programs with IND filings this year, if I had to ask you which one you're personally most excited about, it'd be, IM-1617?
I love all of my children equally, but 1617 is going to be the first one into the clinic. I think, you know, 1340, 1335, we haven't given a ton of detail. Both of those have really exquisite biology and sort of specific, really compelling opportunities. 1617 I think has sort of the broadest range of expression. Just in terms of, like, the opportunity to bring forward a drug that could transform multiple parts of oncology, 1617's pretty exciting.
Got it. Can you elaborate a bit more on that preclinical data with 1617?
You know, we've put some of this in the corporate presentation, but you see activity at fairly low doses across a very wide range of preclinical models. We're very disciplined about how we run mouse models. You know, we're careful not to overdose them. We're careful about choosing challenging models. And if that's your approach, you can actually get some confidence that what you're seeing is real. And that's what we've seen with IM-1617, in addition to, you know, looking at the PK and looking at all of these other properties and so on.
If you disclose the targets for these three solid tumor ADC, IND filings, would we know what the targets are? Would it make a difference?
You would not. You know, honestly, what would happen is you'd probably, like, look at the target, and you'd go pull a academic publication from 10 years that has incorrect IHC expression data or something like that. I'm not saying that's actually out there, but that's just been my experience with published expression data.
We did so much work to characterize these targets internally that even if I told you the name, and even if you went and did a ton of research on it, you don't have access to the data that has made us so excited. When we get to the point where we're ready to disclose, I think there's gonna be a great story with, like, "Look, here's our initial clinical data. Here's all of the preclinical data that made us so excited about this." Even if I told you the name right this moment, it wouldn't mean a whole lot.
Got it. The next three ADCs as if, these four, that we discussed is not enough, when could those approach the clinic?
It's three ADCs this year, and then our goal is to have multiple INDs every year. You know, it's hard to sort of give explicit guidance about what will happen beyond 2026.
Fair enough. Maybe we're up on time, but one question on the radioligand therapy program. Why should people be excited about FAP as a target, and when could the next data disclosure from that program be?
That program is all about the size of opportunity. FAP is expressed in 75% of solid tumors. I think eventually someone will figure out how to crack that target and it will end up being incredibly transformational, and that's the reason we've been willing to take on the complexity of a radiotherapy. We would not be doing a radiotherapy if we thought that the opportunity was like, you know, some tiny little slice of some indication. You know, speaking of the challenges of radiotherapy, we've been working to secure a radiotracer diagnostic that's necessary for patient selection. I think are getting very close to wrapping that up, and we'll dose the first patient pretty shortly.
Wonderful. Briefly, maybe to wrap up the conversation, what do you believe is the most underappreciated aspect of the Immunome story?
I don't know if it's underappreciated, but certainly undervalued is the ADC side of the portfolio. I think we're essentially valued on varegacestat at this point. I think the question I have for investors in 2026 is like, okay, we know that eventually we're going to be getting very meaningful credit for the ADCs, when will that start happening? Just huge opportunity there that people are getting almost for free as an add-on to varegacestat.
Wonderful. Max, thank you for that great presentation and discussion.
Yep. Thank you, Tyler.