Immunome Inc Aktie

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, and there really are 2 pillars for 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 were 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 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 expanding the systemic therapy market within desmoid and why Varegacestat is a really great option. So 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 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 salient questions related to Varegacestat.

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 IM-1021, which is our ROR1 targeted ADC. We 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. And 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 your question 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 3 additional solid tumor programs. All of those are against undisclosed targets. One of those has an active IND, 2 more INDs are planned for the remainder of the year. And all of those incorporate our proprietary TOP1 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 ADCs.

Maybe starting here with Varegacestat. So 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?

So that's a great question. I'll start off by recapping what we had already said at the top line and then dig in on how the data we shared last week really enhanced that story. So what we showed at top line was that we have a very efficacious drug. We've 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. So a very, very efficacious drug.

We also shared very brief safety that said that the profile of Varegacestat is compatible with the class. What we're 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 prespecified endpoint of 12 weeks, but it achieves a clinically meaningful reduction of more than 2 points on the relevant scale as soon as the first evaluation at 4 weeks. And 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 love -- 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 5 or 6 years or desmoid tumor for 5 or 6 years. She's tried different therapies, cryoablation, et cetera. 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 of weeks later, present data showing that clinically meaningful reduction in pain at 4 weeks. That's real. That's something that we see consistently.

And 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 III portion compared to 75% for Nirogacestat.

And 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. And of the 9 where we have not yet seen resolution, 7 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 manageable safety profile.

Could you speak to your commercialization and launch readiness efforts ahead of Varegacestat's approval?

Yes. We have a fantastic commercial team and I'll also emphasize Med Affairs team because it's really the 2 of those that help physicians understand 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 not only did we have the data, but at the KOL dinner that was primarily sarcoma. That's my -- it was incredibly well attended. I think we had 50 or 60 physicians there. It was a couple of 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're having that engagement with KOLs, I think, speaks to the quality of the launch that we're going to have. And we haven't brought our sales force 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 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 sort of -- it's a little premature to say, "Oh, here's where your pricing is going to land." But payers are aware that superior drugs frequently get priced at a premium. 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 launch ramp and cadence? And how are you thinking about just the overall opportunity? What is that peak sales opportunity here?

Yes. 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 had desmoid tumor on their charts in the last year. And at this point, the gamma-secretase inhibitor penetration is fairly low, ballpark. So we're still not quite ready to say, "Oh, here's what peak sales will be." But we see a tremendous opportunity to take the inhibitor market, which I think this year is probably going to be in the $350 million to $400 million range and grow that pretty dramatically.

And 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. And 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.

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

Yes, 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 Ogsiveo 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 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 Parabilis does seem to have an active drug. I think that answering this question, I would really turn to the things that make Varegacestat 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 Varegacestat is an oral once-daily drug compared to twice daily for Niro, but adherence matters in this population. It's a young active population. And 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 and 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. And that seems pretty tough. I'm sure Parabilis 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 we said, it's early, and I don't want to speculate too much. In their S-1, they say they don't intend to run head-to-head trials versus Niro or Varegacestat. So that maybe makes me think that they're looking at either a post-GSI or GSI-ineligible population. I think that GSI has worked very well and Varegacestat, in particular, works very well. So 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. And so 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, 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? And what indications are you going after?

And I think the biggest takeaway from Seagen and part of what made Seagen successful is getting all of those things right. And so 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 NECTIN4. And that's not really where the most unmet need is.

So for us, it starts with identifying novel targets. And 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 TOP1 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. And then 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 2 out of 3 weeks rather than 1 out of 3 like ADCETRIS. 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 fundamental to success.

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

So HC74, it's a TOP1 inhibitor and that is a class that I think has proven its worth. Certainly, starting with DXd, but then with some subsequent programs as well. Among TOP1 inhibitors, the 2 things that really set HC74 apart -- or I'd say, actually 3. So one is that it is not sensitive to efflux. But 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 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%. So you see that 30 percentage point reduction in objective response rate that is driven by expression of efflux. H274, 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. So we see that as really important for overcoming primary resistance in a world where maybe some of your patients have already seen TOP1 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 TOP1 ADCs.

It has a nice bystander activity. That's sort of the second point of differentiation I'd call out. Real-world tumors show a lot of heterogeneity of target expression. And so 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. Well, it can then diffuse into a nearby target negative cell. And that effect is 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 TOP1 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 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, and we're going to see first data probably towards the end of this year. Could you tell us about this asset in the target noting any key points of differentiation from Merck's competing ROR1 ADC? And then frame the expectations for this initial data set in terms of patient numbers and length of follow-up?

So ROR1 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 risk upside for that target. And 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. So the VelosBio molecule uses a linker called vcMMAE, which my colleagues know very well because it was invented at Seagen 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 -- 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 TOP1 payload on it and the potential for a broader therapeutic index. And then 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.

So we're hoping to have a data set. Phase I development is always tricky, right? The Phase III, you can say, well, the 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 an indication of, "Hey, here's the dose we should take forward. Here are -- there's 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 potential.

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 actually 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, we haven't submitted an abstract at this point. So it's a little premature to say. But it won't be -- there will be some backfill in there. It will not simply be us -- it will be the dose escalation portion, but it will not simply be 3 plus 3.

You have 3 additional ADCs in development, all of which are pursuing novel undisclosed targets here. And 1617 received IND clearance recently and you're expected to file INDs for another 2 in mid and late this year. Could you just share additional -- any additional information on these programs and provide updates regarding time lines for data?

Yes. So 1617, that's the one where we have an active IND. 1617 is an incredibly exciting program. The distribution of expression is very broad. So 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 it's, therefore, a little bit less prone to the antigen loss and resistance. So we'll be -- we'll be looking to validate that target. It's -- 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 you an update on them with every quarterly earnings release.

That said, if we get to a point where we have clear signs of activity in a solid -- 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 2 programs, 1340 and 1335, not quite as broadly as 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 closest to the best in terms of what we're doing there just for competitive reasons. But 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?

Yes. So 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. It's expressed in the tumor stroma. And for that reason, you need something with a great bystander effect because you're not targeting the tumor cells themselves. So 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 5 or 6 cell lines. And our goal there is to take out sufficient radiation to the tumor. And a lot of the -- or all of the prior PAP-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. There will be -- 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.

And 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?

Yes. And so our runway guidance is into 2028, and I want to emphasize that, that is sort of uncaveated into 2028, and 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. And so when we say into 1028, 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 would say is, we have incredibly supportive investors who have participated in our equity financing. And 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.

So we -- 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, and we never see the molecule again." But instead have a partner where their capabilities and the terms of the deal makes sense. Sure, we would absolutely consider that.

What I will tell you is that you 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. And so that may be something that is in the puzzle at some point.

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

Yes, thank you for having me.