Great. Good morning, everyone. Thank you for joining us. It's my pleasure to introduce Immunome, and with us we have Max Rosett, 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. There really are two pillars to this story. We view varegacestat, 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 fantastic commercial team, onboarding our med affairs team who are all at ASCO talking with KOLs, 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 physicians and patients have, and really help physicians understand why they should be putting patients on this drug, why they should be expanding the systemic therapy market within desmoid, and why varegacestat is a really great option. I think that as you look at varegacestat 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 priority review or standard review and a PDUFA date. Beyond that, there will be additional data shared at conferences in the second half of the year. You'll also start to hear about the additional work we plan to do to address some of the most salient questions related to varegacestat.
On the ADC side, this is a really, really big year. The big data disclosure is going to be when we put out the first real data set for IM-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. 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. All of those incorporate our proprietary TOPO1 inhibitor, HC74. 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 potential.
Maybe starting here with varegacestat. Last week you shared full phase III RINGSIDE study data for the drug in desmoid 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, OGSIVEO?
That's a great question. I'll start off by just recapping what we had already said at top line and then dig in on how the data we shared last week really enhanced that story. What we showed at top line 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 OGSIVEO in their phase III, with all the caveats of cross-trial comparisons, and a hazard ratio of 0.29. Very, very efficacious drug. We also showed very brief safety that said that the profile of varegacestat 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 varegacestat 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. I would really encourage people to look at that pain reduction, 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. 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, nothing has really worked. Had just kind of resigned herself to living with it. It started growing and there was this dramatic uptick in pain, that became the point where she said, "I need to do something about this." She enrolled in our clinical trial, fortunately was put on the treatment arm and saw a very rapid reduction in pain.
It's great to have that anecdote and then a couple of 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. We showed a 56% ovarian toxicity rate in the phase III portion compared to 75% for nirogacestat. One thing that we really emphasize 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, 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. Overall, we reinforced the efficacy story, we added the pain dimension, which is incredibly important. We talked a bit more about safety, feel that this is a drug that provides tremendous benefit and where through the judicious use of dose reductions it can have a very managed safety profile.
Could you speak to your commercialization and launch readiness efforts ahead of varegacestat's approval?
We have a fantastic commercial team, and I'll also emphasize Med Affairs team, because it's really the two of those that help physicians understand the potential of the drug. 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, not only did we have the data, but at the KOL dinner, that was primarily sarcoma. It was incredibly well attended. I think we had 50 or 60 physicians there.
It was a couple of hours after the presentation. Their reaction to the data was incredibly positive. 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. We haven't brought our sales force on board yet. You do that closer to the PDUFA date. When we bring them on, we're confident that we'll be bringing on the absolute best of the best.
Great. Can you speak to any payer discussions here, how you're thinking about pricing in the context of varegacestat's superior profile in the disease?
Well, I think that your question touches on the key point, right? It's a superior profile. We've had some initial conversations with payers. I think it's a little premature to say, "Oh, here's where pricing is going to land." Payers are aware that superior drugs frequently get priced at a premium. We think that may be an option, but we haven't completed that work yet. It's hard to know the right price until you've really nailed that down.
What are expectations here for launch wrap and cadence and how are you thinking about just the overall opportunity? What is that peak sales opportunity here?
Yeah. The thing I would point you to is the size of the market. Per ICD-10 data, there are 11,000 patients who had desmoid tumor on their charts in the last year. At this point, the gamma-secretase inhibitor penetration is fairly low. Ballpark, 10%. We're still not quite ready to say, "Oh, here's what peak sales will be." We see a tremendous opportunity to take the gamma-secretase inhibitor market, which I think this year is probably going to be in the $350 million-$400 million range, and grow that pretty dramatically. Growing that is going to be about the things I've already touched on, which are taking patients who are on active surveillance and convincing them and convincing their physicians that waiting for progression is not the right paradigm.
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 fix it after the fact.
How do you think just the trajectory of the launch will play out in that context of that?
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 Niro with a substantially better profile.
From the competitive standpoint, Parabilis is developing a desmoid tumor drug with promising, but early data. What are your thoughts on the asset and mechanism targeting the adjacent β-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. Certainly it seems to be top of mind for some investors. As you said, it's an adjacent pathway. I think that we've pretty thoroughly validated the power of gamma-secretase inhibition. Parabilis does seem to have an active drug. I think, though, that answering this question, I would really turn to the things that make varegacestat so special. 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 varegacestat is an oral once-daily drug compared to twice daily for niro. Adherence matters in this population. It's a young, active population.
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. If you take that population and go from saying, "Well, twice daily is too inconvenient for these young active patients," your typical median age is about 40. Then you say, "They're going to go get weekly infusions," that seems pretty tough. I'm sure Parabilis will try to do work on that. 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. I don't want to speculate too much. In their S-1, they did say they don't intend to run head-to-head trials versus niro or varegacestat.
That maybe makes me think that they're looking at either a post-GSI or GSI in eligible population. I think that GSIs work very well, and varegacestat in particular works very well. We'll certainly keep an eye on Parabilis, and we'll learn more along with everyone else.
Pivoting to your ADC platform, which leverages the novel HC74 TOP1 payload and optimized linker technology, help us understand for the company how the learnings from Seagen have informed the design and optimization of Immunome's platform.
I think the biggest lesson from Seagen is that you have to get everything right. If you think about an antibody drug conjugate, it's a complex molecule, and you can sort of go end to end. You start with the target, the antibody, the linker, the payload, ultimately the clinical development strategy. What level are you dosing? How frequently are you dosing? What indications are you going after? I think the biggest takeaway from Seagen, and part of what made Seagen successful, is getting all of those things right. That's what we've tried to do at Immunome, right? It's not just saying, "Hey, HC74 is a pretty special linker payload," which, to be clear, it is, but therefore we're going after TROP2 or Nectin-4. That's not really where the most unmet need is.
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, 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. We're overlaying that with HC74. HC74 is a TOPO1 inhibitor. It has high permeability and resistance to efflux. In most settings, that makes it great. Occasionally, we'll come across a target and the indication combination where we say, "Hey, we really understand HC74's properties. That's not the place to go." There are only a handful of those. You run the trial to understand how best to use this.
One thing that was crucial for Seagen was recognizing that PADCEV needed to be dosed two out of three weeks rather than one out of three, like etcetera. You're never going to use dosing schedule to make a bad drug into a good drug. 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 fundamental to success.
Can you speak to how the platform is differentiated from competitor next-generation ADC approaches?
HC74, it's a TOPO1 inhibitor, that is a class that I think has proven itself. Certainly starting with DXd, with some subsequent programs as well. Among TOPO1 inhibitors, the two things that really set HC74 apart, or I'd say actually three. One is that it is not sensitive to efflux. 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 P-gp and MDR1. As an example, in a study of colorectal cancer patients with HER2 expression who were treated with trastuzumab 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%.
You see that 30 percentage point reduction in objective response rate that is driven by expression of efflux. HC74, we've shown this in a lot of different ways, is not sensitive to those efflux pumps. We had a really fantastic poster about that at the Triple Meeting last year. We see that as really important for overcoming primary resistance, in a world where maybe some of your patients have already seen a TOPO1 ADC. I think that gives you a path to still seeing nice activity, as you prepare to move up in lines and maybe displace other TOPO1 ADCs. It has nice bystander activity. That's the second point of differentiation I'd call out. Real-world tumors show a lot of heterogeneity of target expression.
What bystander effect does is after the ADC is internalized, it binds to a target positive cell, it's internalized, the payload cleaves off and kills that cell. It can then diffuse into a nearby target negative cell. That effect, it's restricted to target negative cells in the tumor microenvironment. That lets you achieve a more uniform effect. Those target negative cells, when you get resistance, those are frequently the ones that grow back and lead to short duration of response. I think those are both really relevant. I would also say that there's some TOPO1 ADCs out there where the linker chemistry is a little bit complicated and clunky. They're doing elaborate things to try to deal with polarity and to prevent aggregation. HC74 and the linker we use are quite a bit cleaner than that.
You have a lead ROR1 ADC candidate, IM-1021, which is currently in phase I dose escalation, in hematologic and solid tumors, 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 ROR1 ADC? Then frame the expectations for this initial data set in terms of patient numbers and length of follow-up.
ROR1's an interesting target. It's, I would say, validated in B-cell lymphomas. It's also present in solid tumors, which is a little bit more of a higher risk upside for that target. The most advanced ROR1 ADC is from Merck. They acquired it from VelosBio in a $2.7 billion transaction. The biggest thing I would point to in terms of differentiation is the ADC platform technology. The VelosBio molecule uses a linker called vc-MMAE, which my colleagues know very well because it was invented at Seagen 25 years ago. That's a phenomenal technology that has really moved the field forward. It was also invented in the Bush administration.
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. You take something that has a more modern proprietary TOPO1 payload on it and the potential for a broader therapeutic index. It's also 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. 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. We're hoping to have a data set.
Phase I development is always tricky, right? At phase III, you can say, "Well, this study's going to read out at this point, and here's exactly what it's going to be." We're hoping to have a data set that gives an indication of, hey, here's the this 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. It will give a picture of where we're going with the program and help people understand its potential.
We're also hoping that that data set will do a lot to help people understand the potential of the payload. 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. That's another thing we're looking for. In terms of number of patients, we haven't submitted an abstract at this point, it's a little premature to say. There will be some backfill in there. It will be the de-escalation portion, but will not simply be three plus three plus.
You have three additional ADCs in development, all of which are pursuing novel undisclosed targets here. IM-1617 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?
IM-1617, that's the one where we have an active IND. IM-1617 is an incredibly exciting program. The distribution of expression is very broad. For that phase I, we're looking at colorectal, we're looking at lung, we're looking at breast. It's a little bit like TROP2, just in terms of being expressed pretty widely in 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. We'll be looking to validate that target. As I said a moment ago, it's hard to know with phase I 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 I programs rather than giving an update on them with every quarterly earnings release. That said, 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'd be pretty interesting, and I think that people will respond well to that. The other two programs, IM-1340 and IM-1335, not quite as broadly as expressed as 1617, but 1340 in particular still has multi-indication potential. That IND is on track.
IM-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. Once we're able to talk about that ADC in more detail, we did a really, really nice job of designing that ADC. We took a target where a prior ADC had shown 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 radioligand that's recently entered phase I?
Yeah. We have an active trial for IM-3050. The premise of that molecule is that FAP is a great target. It's expressed in 75% of solid tumors, but it's expressed in the tumor stroma. For that reason, you need something with a great bystander effect because you're not targeting the tumor cells themselves. 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 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. 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. Our runway guidance is into 2028, I want to emphasize that is sort of uncaveated into 2028. That's supporting the commercial launch, that's supporting all of these programs. It includes the potential of moving forward IM-1021 into larger studies and so on. When we say into 10/28, it's with a pretty expansive vision. In terms of business development, this is something that Seagen did quite well, was finding partners. What I will say is we have incredibly supportive investors who have participated in our equity financing. For that reason, 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.
If at some point we have a partner where it's not just sort of, hey, they provide a little bit of cash and tiny little royalties, we never see the molecule again, but instead have a partner where their capabilities, the terms of the deal make sense, sure, we would absolutely consider that. 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 Tubulis, that there still is demand for ADC platforms and programs. 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.