Goldman Sachs 47th Annual Global Healthcare Conference

Great. Good morning, everyone. Thank you for joining us. It's my pleasure to introduce Immunome, and with us we have Max Rosette, CFO of the company. Max, to start here, thank you for joining us. Immunome is a targeted oncology company developing third-generation ADCs. At the same time, you have a commercial asset that's headed to launch here. Can you give us a high-level overview of the company and where your programs stand and what updates we can anticipate in the second half or over the next 12 to 18 months.

Of course. Thank you for having me here. It's a pleasure to be here. As you said, Immunome is a targeted oncology company, and there really are two pillars to this story. We view varagastestep, our gamma secretase inhibitor, for which we recently submitted an NDA, as a fantastic asset. We're really excited to be preparing to launch that over the remainder of this year. That launch preparation, I think, has a couple of different streams. One is just operational, building a thin tapio alz and just doing everything that needs to be done logistically. The other thing I would flag is continuing to share data that will address the questions that investigators or that physicians and patients have and really help physicians understand why they should be putting patients on this drug, why they should be in the market within dasmoid, and why varagasostat is a really great option. So I think that as you look at varagasostat over the remainder of this year and into next year, by the end of this month, we should find out if the FDA has filed the application and given us a priority review or standard review and a PDUFA date. And then beyond that, there will be additional data shared at conferences in the second half of the year. And you'll also start to hear about the additional work we plan to do to address some of the most salient questions related to varic acid stats. On the ADC side, this is a really, really big year. So the big data disclosure is going to be when we put out the first real data set for IOM 1021, which is our ROR1 targeted ADC. We've said that's coming at a medical conference in the second half of this year. We've already disclosed that we've seen objective responses at multiple dose levels in B-cell lymphoma. So when we put out that data set, our goal is not simply to say, okay, we've seen a little bit of activity, but to answer questions about dose and schedule and maybe give an indication of where within B-cell lymphoma we plan to take that program. As far as the rest of the ADC portfolio, we have three additional solid tumor programs. All of those are against undisclosed targets. One of those has an active IND. Two more INDs are planned for the remainder of the year. And all of those incorporate our proprietary Topo-1 inhibitor HC74. So the second half of the year is really going to be about getting those trials up and running because I think many of our investors and certainly many of our employees are with Immunome because of the long-term ADC.

Maybe starting here with Baragasestat. So last week you shared full Phase III ringside study data for the drug and decimate tumors at ASCO, which included key quality of life metrics. Can you walk us through what was most meaningful from that data set in the context of competitor or Stivio?

So that's a great question. I'll start off by just recapping what we had already said at Topline and then dig in on how the data we shared last week really enhanced that story. So what we showed at Topline was that we have a very efficacious drug. We showed a 56% objective response rate. We showed an 83% median best tumor volume reduction. We showed a hazard ratio of 0.16, 84% reduction in the risk of progression. The comparable numbers, 41% for Oxivio in their phase 3 with all the caveats of cross-trial comparisons and a hazard ratio. So very, very efficacious drug. We also showed very brief safety that said that the profile of variegastastat is compatible with the class. What we were able to show at ASCO was not just more data on each of those points, although we were able to give more detail, but to touch on things that really, really matter to patients like these patient-reported outcomes. We were incredibly pleased that not only does variegastastat show pain reduction at the pre-specified endpoint of 12 weeks, but it achieves a clinically meaningful reduction of more than two points on the relevant scale as soon as the first evaluation at four weeks. And I would really encourage people to look at that pain reduction, you know, not just as something that makes it a better drug, but something that really speaks to why physicians and patients initiate treatment. We actually had a patient from the study come by our office, which is fantastic. We're in this to help patients. To have a patient come by the office and talk to our team about how her life has been made better is always really compelling. But one of the things I took away from that presentation is she's been dealing with desmoid tumors for five or six years, or a desmoid tumor for five or six years. She's tried different therapies, cryoablation, et cetera. and nothing has really worked, and had just kind of resigned herself to living with it. But then it started growing, and there was this dramatic uptick in pain. And that became the point where she said, I need to do something about this. And so she enrolled in our clinical trial and fortunately was put on the treatment arm and saw a very, very rapid reduction in pain. And so it's great to have that anecdote and then a couple weeks later present data showing that clinically meaningful reduction in pain at four weeks. That's real. That's something that we see consistently. The other thing I would talk about is that we're able to show more data on safety. Certainly, investors have given a lot of attention to the question of ovarian toxicity, the known class effect. There's a fairly straightforward mechanism related to gamma secretase inhibition. And we showed a 56% ovarian toxicity rate in the phase 3 portion compared to 75% for coronary agassistat. One thing that we really emphasized is we've seen resolution in 11 of those 20 patients. We expect to see resolution in essentially all of them based on the mechanism. And of the nine where we have not yet seen resolution, seven of those are still on treatment. That speaks to another key point, which is although this toxicity has gotten a lot of attention, overall, we saw no discontinuations related to ovarian toxicity. So overall, we reinforced the efficacy story. We added the pain dimension, which is incredibly important. We talked a bit more about safety and feel that this is a drug that provides tremendous benefit and where, through the judicious use of dose reductions, it can have a very, very management.

Do you speak to your commercialization and launch readiness efforts ahead of Vargasa's approval?

Yeah, we have a fantastic commercial team, and I'll also emphasize MetaFair's team because it's really the two of those that help physicians understand the principle of the drug. So we've been building our commercial team, a lot of people who previously worked together at a common employer and have launched drugs together in the past. ASCO, I think, was, you know, not only did we have the data, but KOL dinner that was primarily sarcoma and chasmoid. It was incredibly well attended. I think we had 50 or 60 physicians there. It was a couple hours after the presentation, and their reaction to the data was incredibly positive. And the work that went into organizing that event and making sure that we were having that engagement with KOLs, I think, speaks to the quality of the launch that we're going to have. And, you know, we haven't brought our Salesforce on board yet. you do that closer to the PDUFA date. But when we bring them on, we're confident that we'll be

bringing on the absolute best of the best. Great. And can you speak to any payer discussions here, how you're thinking about pricing in the context of variegastastat's superior profile in the

disease? Well, I think that your question touches on the key point, right? It's a superior profile. You know, we've had some initial conversations with payers. I think it's sort of too, it's a little premature to say, oh, here's where your price is. And we think that that may be an option, but we haven't completed that work yet. And it's hard to know the right price until you've really nailed that down.

And what are expectations here for LaunchRap and Cadence? And how are you thinking about just the overall opportunity? What is that peak sales opportunity here?

Yeah, so the thing I would point you to is the size of the market. Per ICD-10 data, there are 11,000 patients who have desmoid tumors. At this point, the gamma secretation ballpark. We're still not quite ready to say, oh, here's what peak sales will be. But we see a tremendous opportunity to take, probably going to be in the $350 million to $400 million range. grow that pretty dramatically. And growing that is going to be about the things I've already touched, which are taking patients who are on active surveillance and convincing them or convincing their physicians that waiting for progression is not instead. You can take a patient and give them a drug that is safe, that is convenient, that is efficacious, and will address any symptoms that they do have in a more proactive way, rather than waiting for progression, waiting for them to experience pain, waiting for their lives to get worse, and then trying to...

And how do you think the trajectory of the launch will play out in that context of that?

You know, that's work that we're still doing. We think that we have a really fantastic drug, and we think that there's unmet need. We're launching a couple of years after Oxivio with a substantially better profile.

From the competitive standpoint, Parabolus is developing a desmoid tumor drug with promising but early data. What are your thoughts on the asset and mechanism targeting the adjacent B-catenin pathway versus gamma-secretase for desmoid tumors?

That is a natural question and one that we're getting. I've heard that maybe their IPO is happening this week. So certainly it seems to be top of mind for some investors. As you said, it's an adjacent pathway, and I think that we've pretty thoroughly validated the power of gamma secretase inhibition, and parabolis does seem to have an active drug. I think, though, that answering this question, I would really turn to the things that make varagastastat so special. So there's tumor volume reduction, as we've already talked about, but we're also really pleased that we have demonstrated that substantial pain reduction and that that occurs quickly. Convenience also matters tremendously to these patients. We haven't talked yet about the fact that varagastat is an oral once-daily drug compared to twice-daily for Nero. But adherence matters in this population. It's a young, active population. So we've been pleased and at times maybe a little bit surprised by how vehement physicians are that once daily is substantially better than twice daily. And so if you take that population, go from saying, well, twice daily is too inconvenient for these young active patients. Your typical median age is about 40. And then you say, so they're going to go get weekly infusions. That seems pretty tough. I'm sure Parabalus will try to do work on that. And then the other thing I would point out is they have not given a ton of clarity on what their development path is. It's tough to comment. As you said, it's early and I don't want to speculate too much. In their S1, they did say they don't intend to run head-to-head trials versus Miro or Varagastastat. So that maybe makes me think that they're looking at either a post-GSI or GSI ineligible population. I think that GSIs work very well, and Varagastastat in particular works very well. So we'll certainly keep an eye on Parablas. We'll learn more along with everyone else.

Moving to your ADC platform, which leverages the novel AHC-74-1 payload and optimized linker technology, help us understand for the company how the learnings from CGen have informed the design and optimization of Immunome's platform.

I think the biggest lesson from CGen is that you have to get everything right. So if you think about an antibody drug conjugate, it's a complex molecule, and you can sort of go end to end. You know, you start with the target, and then the antibody, the linker, the payload, and then ultimately the clinical development strategy. So what level are you dosing? How frequently are you dosing? What indications are you going after? And I think the biggest takeaway from getting all of those, and so that's what we've tried to do. ad-immuno, right? It's not just saying, hey, HC74 is a pretty special link or payload, which to be clear, it is. But therefore, we're going after Trope 2 or Nectin 4. That's not really where the most unmet need is. So for us, it starts with identifying novel targets. One stat that I like is that 50% of clinical stage ADCs go after the same 10 targets, and we're staying away from those 10 targets. We're doing really fantastic target discovery biology. We're doing a ton of IHC work. We're understanding the spatial distribution and the biological properties beyond expression that make for a really great ADC target. And then we're overlaying that with HC74. So HC74 is a Topa-1 inhibitor. It has high permeability and resistance to e-flux. In most settings, that makes it great. Occasionally, we'll come across a target and indication combination where we say, hey, we really understand HC74's properties. That's not the place. And then you run the trial to understand how best to use this. One thing that was crucial for Cgen was recognizing that PADSUB needed to be dosed two out of three weeks rather than one out of three, like, et cetera. And you're never going to use dosing schedule to make a bad drug into a good drug. But if you've designed a good ADC, found the right indications, and get your dosing and your clinical development plan right, that's going to be fun.

Can you speak to how the platform is differentiated from competitor next-generation ADC approaches?

You know, HC74, it's a topo-1 inhibitor, and that is a class that I think has proven it's for DXD, but does that as well. Among topo-1 inhibitors, the two things that really set HC74 apart, or I'd say actually three. So one is that it is not sensitive to efflux. So if you look at DXD, it is very clear that a major component of resistance to DXD ADCs is the upregulation of efflux pumps like PGP and MDR1. And so as an example, in a study of colorectal cancer patients with HER2 expression who were treated with tristuzumab DXD, the objective response rate for those with low efflux expression is 47%. The objective response rate for those with high efflux expression is 17%, but it's driven by expression of efflux. H274, we've shown this in a lot of different ways, is not sensitive to those efflux pumps. So we see that as really important to avoid maybe some of your 1ADC. It has nice bystander activity. That's sort of the second point of different real-world tumors show a lot of heterogeneity. And so what bystander effect does is after the ADC, well, it can then diffuse into a nearby target negative cell. And that effect, it's restricted to target negative cells. in the tumor microenvironment, but that lets you sort of achieve a more uniform effect. And those target negative cells, when you get resistance, those are frequently the ones that sort of grow back and lead to short duration of response. So I think those are both really relevant. I would also say that there's some topo-1 ADCs out there where the linker chemistry is a little bit complicated and clunky. They're sort of doing elaborate things to try to deal with polarity and to prevent aggregation. And H274 and the linker we use are quite a bit cleaner than that.

You have a lead ROR1 ADC candidate, IM1021, which is currently in Phase I dose escalation in hematologic and solid tumors, and we're going to see first data probably towards the end of this year. Could you tell us about this asset and the target noting any key points of differentiation from Merck's competing War I ADC and then frame the expectations for this initial data set in terms of patient numbers and length of follow-up?

So War I is an interesting target. It's, I would say, validated in B cell lymphomas. It's also present in solid tumors, which is sort of a little bit more of a higher. And the MIS Advanced ROR1 ADC is from Merck. They acquired it from Velos Bio in a $2.7 billion transaction. The biggest thing I would point to in terms of differentiation is the ADC platform technology. So the Velos biomolecule uses a linker called VCMMAE, which my colleagues know very well because it was invented at CGEN 25 years ago. And that's a phenomenal technology that has really moved the field forward. It was also invented in the Bush administration. And so I think that if you take a target where there is some activity, But you look at that molecule, and it has a very, very narrow therapeutic index, or maybe no therapeutic index. And you take something that has a more modern, proprietary topo-1 payload on it and the potential for a broader therapeutic index. And then it's also, you know, all of the things I talked about, the optimized antibody and so on, and running a good study. I would say that that is the differentiation from Merck. We don't necessarily view that Merck molecule as the bar. You know, our goal is not to be the best ROR1 ADC. It's to have a really great lymphoma drug. As we come into the end of this year, as I mentioned earlier, we've already said that we've seen objective responses. So we're hoping to have a data set. Phase I development is always tricky, right? At Phase III, you can say, well, this study is going to read out at this point, and here's exactly what it's going to be. But we're hoping to have a data set that gives, hey, here's the dose we should take forward. Here's the activity we're seeing in different kinds of B-cell lymphoma. Here are maybe the expansion cohorts that we're going to run or have already started enrolling. And it will give a picture of where we're going with the program and help people understand it's central. We're also hoping that that data set will do a lot to help people understand the potential of the platform. I'm not saying that every question about HC74 can be addressed, especially because we have other HC74 programs that we're currently developing in solid tumors, and some of those properties may be most relevant to solid tumors. But that's another thing we're looking for. In terms of number of patients, you know, we haven't admitted an abstract at this point, so it's a little premature to say, but it won't be, there will be some back. It will be the desescalation portion, but it will not simply be 3 plus 3 plus.

You have three additional ADCs in development, all of which are pursuing novel undisclosed targets here, and 16-17 received IND clearance recently. And you're expected to file INDs for another two in mid and late this year. Could you just share any additional information on these programs and provide updates regarding timelines for data?

So 16-17, that's the one where we have an active IND. 16-17 is an incredibly exciting program. The distribution of expression is very broad. So for that phase one, we're looking at colorectal, we're looking at lung, we're looking at breast. It's a little bit like trope two, just in terms of being expressed pretty widely and really interesting indications with a lot of unmet need. The receptor biology there is really interesting. We haven't disclosed the target for competitive reasons, but it's a receptor that plays an active role in tumor biology, and I think is therefore a little bit less prone to antigen loss and resistance. So we'll be looking to validate that target. As I said a moment ago, it's hard to know with phase one exactly what you're going to see and when the right time point to share data is. I think one of the luxuries we have as a company that's preparing to launch a commercial product is we can sort of wait until we have more of an answer on our phase one programs rather than giving an update on them with every quarterly earnings release. That said, you know, if we get to a point where we have clear signs of activity with a solid tumor ADC with a target that nobody else is going after, I think that would be pretty interesting, and I think that people will respond well to that. And then the other two programs, 1340 and 1335, not quite as broadly expressed as 1617, but 1340 in particular still has multi-indication potential. That IND is on track. And then 1335, that's the one where we've sort of had to play it closest to the vest in terms of what we're doing there just for competitive reasons. But once we're able to talk about that in more detail, we did a really, really nice job of designing that ADC. We took a target where a prior ADC had filmed some activity. We identified why that ADC hadn't worked, and we went in and built a really great molecule.

Anything that you want to highlight regarding your radio ligand that's recently entered phase one?

Yeah, so we have an active trial for IM-30. The premise of that molecule is that TAP is a great target, 75% of solid tumors, but it's expressed. And for that reason, you need something with a great bystander effect because you're not targeting the tumor. We've built that radiotherapy using a beta emitter, lutetium, because that can kill in sort of a wide blast radius around the target of sort of five or six cell lengths. Our goal there is to get sufficient radiation to the tumor. All of the prior FAP-targeted therapies simply haven't resided in the tumor long enough because you need the drug to sit there long enough for the isotope to decay. So we'll be, you know, we'll see what the initial dosimetry looks like. We'll be looking for responses, and we'll provide an update when we have one.

Just a final question here, Max. Speak to the CASH runway in the context of these programs you're running, but also kind of strategy from a BD perspective. Yeah.

Yeah. So our runway guidance is into 2028, and I want to emphasize that that is sort of a un-caveated into 2028. That's supporting the commercial launch. That's supporting all of these programs. It includes the potential of moving forward 1021 into larger studies and so on. So when we say into 1028, it's with a pretty expansive vision. You know, in terms of business development, this is something that CJEN did quite well, was finding partners. What I would say is we have incredibly supportive investors who have participated in our equity financing. And for that reason, you know, we've had opportunities to do deals and we've passed on them because they, I don't think, fully reflected the value of what we're doing. So we, you know, if at some point we have a partner where it's not just sort of, hey, they provide a little bit of cash and, you know, tiny little royalties and we never see the molecule again, but instead have a partner where their capabilities and the terms of the deal make sense, sure, we would absolutely consider that. But what I will tell you is that people are aware of what we're doing on the ADC side, investors, but also pharma companies are aware of what we're doing on the ADC side. I think it is pretty special. I think that we've seen most recently with Tubulus that there still is demand for ADC platforms and programs. And so that may be something that fits into the puzzle at some point.

Well, with that, thank you so much. Really appreciate the time today.

Yeah, thank you for having me.