All right, with that, we'll go ahead and get started. Good morning, everyone. Hope everyone had a great weekend. My name's Tyler Grandbjørn here, Senior Biotech Analyst at TD Cowen. Thank you very much for attending TD Cowen's sixth Annual Oncology Innovation Summit. For one of the first sessions of this morning, we have a Q&A virtual fireside chat with Immunome, and it's my pleasure to introduce Max Rosett, the Chief Financial Officer of Immunome. Max, it's a privilege to have you here. Thank you very much for joining me. Thank you very much, Tyler. I don't think the Q&A will be very surprising as we go through the story here, but if you guys have any questions for those who are logged in live, you can shoot them to me by email, and I'll see if I can get them asked. We'll go ahead and start with your most advanced asset, varegacestat, formerly known as AL102, in desmoid tumors. DT space has clearly become pretty active here lately, especially following the recently announced acquisition of SpringWorks for over $3 billion. Max, maybe you could start by walking through how that deal was consummated and how varegacestat differs from SpringWorks or OGSIVEO. Yeah, so, you know, we were fortunate enough to acquire varegacestat about a year and a half ago at this point. We were drawn from day one to the superior potency that this molecule offers. That shows a long variety of dimensions. It's the same target as OGSIVEO, and obviously the same mechanism of action. The molecule itself is quite a bit more potent. It's administered once a day at 1.2 milligrams compared to 150 twice a day for SpringWorks. When we look at our phase II data, we saw really compelling activity. Objective response rate is the first place that we would point to to see that. We saw intent to treat, intent to treat, ORR of 64% compared to 41% for SpringWorks in their phase III, with all the caveats that go with cross-trial comparisons. One common pushback we'll get is that, okay, your phase II, that 1.2 cohort was only 14 patients to give you that 64%. If you broaden out to all 42 patients in the phase II, two-thirds of which got what we view to be suboptimal dosage, you still see a 54% ORR in that larger group. Objective response rate is one way of capturing the superior efficacy. If you really think about desmoid tumor, let's take a moment to talk about this disease. Desmoid tumor is, desmoid tumors are a terrible disease. They have a huge quality of life impact. They force people to leave work. People say things like, "I can't pick up my child anymore." They are typically not fatal. This is a disease where focusing on things like progression-free survival or certainly overall survival does not really get at the core of what patients and their physicians are looking at. This is something we have heard very consistently. For regulatory reasons, the primary endpoint of our trial is progression-free survival. And we do think, you know, if you have a big tumor in your neck, certainly you do not want it to get bigger and potentially invade nearby tissues. But it is not like, you know, metastatic pancreatic cancer where growth is a proxy for overall survival. So increasingly, we have focused on some of the other measures of response. Not just objective response, but one of, one of the posters we have at [Alzaco] really highlights tumor volume as a measurement for efficacy in this class. The example that we've taken to give to giving and the numbers come pretty close to aligning, with this example. Let's say you have a softball-sized tumor in your neck and you take OGSIVEO. The median reduction in tumor volume is 59%. That's about a softball to a baseball. If you take varegacestat based on the phase III or phase II data, you have a median reduction of 88%. That takes it to a golf ball. In a traditional oncology setting, something like tumor volume may not seem as relevant, but given the nature of this disease, we see ORR and especially tumor volume reduction as really compelling indicators of a more efficacious drug that will lead to better outcomes for patients. Okay, thanks for that. That's very helpful. You guided the top line data from phase III RINGSIDE trial in the second half of this year. Maybe you could just elaborate on what gives you guys confidence in the timing of that readout, during the second half of the year and what we should expect from the top line update. Yeah, so we've had that data drop for more than a year now and reiterated it as recently as two weeks ago when we filed our earnings. Event-driven studies are inherently unpredictable. I think in the case of this study, we've tried to be transparent that, if we get to a point where we feel like events are not continuing to accrue at a meaningful rate, and that overall, the data is mature, we would consider going to the FDA and having a discussion with them about stopping with fewer than a pre-specified number of events. You know, we are not yet at the point where we're saying that that is how it's going to play out. When we think about what it will take for this data set to be mature, we feel pretty confident that we will have that in the second half of this year one way or another. That gives us more confidence than we might usually have with an event-driven study. The natural question that people ask to follow up on that is statistical power, you know, are you guys saying you're going to underpower this study? I'd remind people that it's a placebo-controlled study, and that if this drug is indeed more active than OGSIVEO, which is something we believe quite strongly, statistical power versus the placebo is not going to be a primary concern. Okay. When we get that top line update, should we just expect you guys to say that the primary endpoint was achieved, you know, and statistically significant, or do you expect to give more detail in terms of what was observed in the trial or potentially even give secondary endpoints? Yeah, we haven't specifically committed that side. I think you just heard me talk for about five minutes about how important we think secondary endpoints are for understanding this data. You know, our goal is to be able to present this at a major medical meeting and hold back enough information that we can do so. Nonetheless, we want to put out a useful top line data package. Okay. All right. And, you know, based on your conversations with those in the space, in the desmoid tumor space and KOLs, what do you all believe? I mean, obviously, if you replicate the phase II data in phase III, that's going to be very meaningful for patients. Assuming that, you know, maybe it does come in a little bit in phase III, what is the minimum that you all believe varegacestat needs to show in order to be differentiated and competitive versus OGSIVEO, when we see the data? Yeah, it's an important question. I think the way you ask that question highlights a really important point, which is the natural thing to do is go to our phase II data because that was superb data and say that's the bar. I would really emphasize that the bar is the data that SpringWorks shared, the 41% ORR and the 58% or sorry, 59% tumor volume reduction. Our goal is to meaningfully improve on those. I think that given that you're looking at multiple metrics and you're looking at the safety profile, and then we also have the advantage of being dosed once daily instead of twice daily, which has turned out to be. KOLs keep telling us that that's more important than we anticipated. It's hard to say exactly what the number is. I'd certainly love to see ORR in the 50s. I'd love to see a tumor volume reduction that is substantially higher than that 59% figure among the valuable patients. I do think that there's a little bit of incongruity here. You know, you started off by talking about the SpringWorks acquisition, $3.5 billion of enterprise value. I don't know enough about their NF1 drug to really portion it out, but I've seen from analysts that that's maybe 60%, two-thirds of the value. A multi-billion dollar acquisition for OGSIVEO. If we have a drug that is undeniably three years behind, but a drug that is, you know, where physicians are saying to their patients, "On OGSIVEO, you're more likely to not respond than to respond. On varegacestat, you're more likely to respond than not. On OGSIVEO, you're going to go from a softball to a baseball. On varegacestat, you're going to go to something more like a golf ball. I just have a very hard time reconciling enterprise value, even adjusting for the fact that we don't have phase III and the fact that we're behind with that multi-billion dollar valuation for Xivio. To say we're excited to see this data in the second half of the year is a tremendous understatement. Great. In terms of, you know, beyond response rate, PFS, tumor volume, are there any other endpoints that you all feel are particularly meaningful or specific domains where it could differentiate in terms of like time to response or depth of response or I guess depth of response is tumor volume, but time to. Yeah, I would think depth of response is tumor volume. There will be a PRO secondary endpoint, you know, I mean, to be determined in terms of one that's released. Pain is a pain, pain is a really big deal for these patients, and having quick relief of pain can be something that helps restore functionality and leads to good outcomes. I would highlight that PRO. Overall, I think there are a lot of different ways or a lot of different pieces to the puzzle that capture superior efficacy. Okay. Maybe to wrap up the varegacestat discussion, I guess if OGSIVEO was a, you know, a multi-billion dollar portion of that $3.5 billion EV, it would suggest, you know, using like a 4x multiple that desmoid tumor market is at least several hundred million. Just curious to get your latest thoughts on the opportunity for the desmoid tumor space in general and in particular varegacestat. Yeah, we continue to be incredibly optimistic about the size of this market. Certainly, OGSIVEO had a challenging first quarter. I think hard to know why. They had already signed the merger agreement at the time that they announced it, so they did not give any color. You can speculate around things like a first quarter payer dynamics for an oral drug. What I would point out is that if you go and look at the history of the merger, when OGSIVEO's sales numbers came out for the first quarter, that did not derail the merger or apparently impact the press in a meaningful way. We feel like that data point, whatever the explanation is, it is not something that raises fundamental concerns about this market. Prior to that quarter, SpringWorks was already, they did something like $170 million in their first year selling this drug. We think there's tremendous upside from there. You know, I'd point you at our enterprise value to highlight the disconnect that I perceive. Okay, great. Now let's shift to the discussion of ADCs, the core, the heart and soul of Immunome and the future of the company. The space continues to expand rapidly, obviously, dominated by pharma to a large extent. How does Immunome plan to differentiate itself? Maybe you could briefly start by describing Immunome's discovery efforts. Yeah, so Immunome is a little bit unusual for a company of our stage in terms of the caliber of talent we've been able to assemble on the ADC side. I would posit to you that there has never been a better time and place to hire ADC talent than Bothell, Washington, over the 12 months after the Pfizer Seagen merger closed. We started construction on our offices about 30 days after that merger closed. We have been able to assemble really fantastic people at every step of the value chain for creating ADC. Fantastic discovery team, translational clinical operations, CMC. You know, in the interest of time, I will not recite the achievements of everyone I work with, not least of all Clay. We've been able to assemble a ton of expertise on the ADC side. The play, the way that has been instantiated, first there's operational excellence. We were able to get a ROR1 ADC into the clinic. We were able to get that IND cleared a quarter ahead of schedule, just because we have a very good tech ops team and a great development group. In terms of how that shows up in strategy, a few things. First, we think the starting point is always best-in-class technology. I'll talk a little bit more about our proprietary Topo 1 HC74 in a moment. Suffice it to say that Topo 1s are a great class. They are a crowded class. Even so, within that class, HC74 shows. It has some really great differentiated characteristics. I think one thing to look for over the course of this year is us continuing to map those out a little bit more. The second thing is that we are not afraid of going after novel targets or under-explored targets. I think that's something you see a lot of is a company says, "Oh, we have a fantastic linker payload." The next thing they say is, "So we're going to slap it on trastuzumab." We don't see white space there. We don't see tremendous unmet patient need. Is there a better drug than Enhertu out there? Probably in the same way that Enhertu was a meaningful improvement on Kadcyla. Is there a better drug than Padcev out there for bladder cancer? I think I have to say yes. Some of my colleagues who helped develop Padcev think Padcev's pretty great. We believe that there's room to improve on some of those, perhaps. You're going to be doing huge trials that may take a long time. In the end, they might not work. We have looked around and said, "Hey, look, before Neptune 4 was Neptune 4, nobody had heard of it." We have people who are capable of doing really rigorous target validation, understanding, you know, not just ADC targets as sort of homing beacons for your heat-seeking missiles, but instead as biologically relevant targets that play a role in disease and that interact in, frankly, quite complicated ways with appropriately designed ADCs. I think that having the expertise and, frankly, the courage to go after targets that people are not familiar with is sort of the second point of our strategy. You need to have the right technology, but you need to go somewhere that is less crowded. You know, over the long term, certainly we are working to expand our toolbox beyond HC74 and Topo 1. We think that there is a lot of creative work left to be done to define new approaches to ADCs and are investing our time in that. The ADC story, Tyler, you've been covering us for about a year and a half now, and it has gotten substantially more advanced over that time period. With our IM1021, our ROR1 program starting this escalation in February, it is becoming, it's going to be a big year, or let's say a big 12 months looking forward from now on the ADC side, not just the varegacestat side. Okay, thanks for that. We've got maybe five plus minutes left, but I want to be sure to hit on HC74, ROR1, the other novel ADCs, as well as FAP radioligand. Maybe just briefly before we get into the specific programs, maybe you could just double tap on what makes HC74 special relative to all the other Topo 1s out there. Yeah, so briefly, you know, HC74, I would point to a couple of sort of non-obvious characteristics that really drive differentiation from other Topo 1s. These are the kind of things that are not obviously important when you're first looking into the ADC space. The more time you spend, the more you understand how they really drive efficacy in real-world settings, how they can help overcome some of the resistance that you see with Topo 1s. The two things I would point to, again, just trying to be efficient, one is permeability, that leads to enhanced bystander effect. In a real world, in a mouse model, you may have a nice homogenous tumor. In an actual patient, especially one who has seen prior lines of chemo, you may have a target positive cell and extra target negative cell. Permeability gives you a way where after the ADC has been cleaved in the tumor environment, it allows the payload to diffuse into target negative cells, which we believe can have a real impact on the efficacy. Efflux resistance, we know that efflux is a substantial part of the story for how tumors become resistant to Topo 1 ADCs. We see a superior efflux ratio of about 9.8 compared to 78 for DXT, the payload in Enhertu. We have some nice data that we're hoping to share sometime soon, about efficacy in both chemo-resistant cell lines and then also chemo-resistant mouse models. Real differentiation there. Okay, that's helpful. Let's move to IM1021, your ROR1 ADC, mentioned that it just recently entered phase I. Maybe just briefly, you could explain why you guys chose to bring this asset in, why you like the target ROR1, and when we might see initial data. Yeah, again, being very brief about it, ROR1 is a target with a lot of potential. Velos Bio demonstrated that potential in lymphoma and were acquired by Janssen for that asset by Janssen for $2.75 billion about four and a half years back. Our observation is that that ADC has the vcMMAE linker payload that's ubiquitous to all of Seagen's molecules. They started to scrap the first antibody they found, they slapped that on it, and they were still able to see good efficacy. We believe that our molecule is a substantially better molecule in terms of antibody properties, in terms of linker payload, and has potential both for less toxicity, for efficacy as a lymphoma monotherapy, and then also a tremendous upside on the solid tumor side. As far as timing of data, we're not going to sort of trickle out data, you know, sort of get one response out of three patients and go to the world and say, hey, that's 33%. So we're not yet promised. I think we will have data this year, but we will wait. We will choose the right venue to share that data. Okay. I guess moving to the three novel solid tumor ADCs that have been disclosed in the second half of last year, 1617, 1340, and 1335, ongoing IND-enabling studies. Can you give us any sort of color as to when we might see these enter the clinic, when they might be ready to start dosing patients? Mm-hmm. No firm guidance on that, but again, extremely experienced tech ops team that has pride on 20 different ADC INDs, so we're trying to move this forward, in line with that kind of timeline, and we did start that work in Q4 or Q1. Okay. We understand you have another six additional ADCs behind those ongoing lead optimization. Is that accurate? Maybe you could just give another more color around where those are at. Yeah, you know, the number varies day to day, but we have additional candidates that are, you know, some of them fail. You have to try a lot of things. We expect to be able to nominate additional candidates. You know, it's fit to be a company with multiple INDs per year. Okay. Maybe we'll move to the FAP radioligand therapy. You utilize this lutetium payload. Maybe you could briefly describe why FAP is a target that you guys are interested in and what work has been done ahead of the phase I initiation that you feel made it well prepared to enter the clinic. FAP, fantastic target, expressing 75% of solid tumors. The challenge is it's on the fibroblasts in the tumor primarily, not the actual cancer cells. You need something with a really robust bystander effect. A lutetium payload radiotherapy gives you that. Lutetium can, you know, when it decays, those beta particles can kill cells four or five cell lengths away. Starting a phase I trial is quite challenging in the radiotherapy space. It's easier than it was five years ago or even three years ago. It's taking a lot of time and effort, but we are on track to start that trial at some point in the second half of this year. Okay, great. Just, maybe you could discuss briefly your CAS position and if we should expect any more business development activity in the near future since you guys have been so active, following the merger. Yeah, we filed with 317 at the end of Q1, and that gives us runway into 2027. On the business development side, you know, if we come across another varegacestat that we can get for about $50 million upfront, we will do that kind of deal again. We would also love to find, I'm not going to say a nondiluted deal, I'm going to say the right nondiluted deal. We have a huge portfolio and finding a partner who can be a real value add to help us advance it more aggressively could be a great option. Okay, great. With that, since we're out of time, we'll go ahead and wrap up. Max, thank you very much for the discussion, and thank you to investors for attending. Have a great rest of the day. Thank you, Tyler.