Great. Welcome everyone to the Piper Sandler Healthcare Conference. My name is Biren Amin. I'm one of the Managing Directors here on the Piper platform. I'd like to welcome our next company, Immunome. And we have their Chief Financial Officer, Max Rosett. Welcome, Max.
Thanks for having me.
Immunome, I mean, a lot going on over the last, you know, 12- 18 months. You know, you've acquired AL102, also acquired the ROR1 ADC from Zentalis, and a discovery platform of more than, you know, 25, 30 targets. So it feels like that, and then bringing on, you know, a lot of the former senior executives from Seagen. So it feels like this is like the next-gen Seagen. Is that like a fair characterization?
I'm not sure I can go on the record as saying yes to that, but we certainly are hoping to build the next great ADC company. It's really been an opportunity to, on the day of the merger between the predecessor Immunome and the private company, Morphimmune, closed, and Clay became CEO. He was the only employee that we had in the Seattle area, and now we're up over 100. So we've been able to build a really strong team. You know, those asset acquisitions that you announced, AL102, that you just referenced, AL102 is a really fantastic asset, and we were fortunate to be able to bring that in so quickly. It's added a lot of value, and I think has let us mature as a company.
But over the long term, we do view ourselves as an ADC company, and are going to be very focused on that for discovery and organic pipeline growth.
So, given, I guess, the focus on the ADC platform, what was the rationale for acquiring AL102 from Ayala, that's a small molecule gamma secretase inhibitor that you're developing for desmoid tumors in phase three studies?
Yeah. It's a fair question. I think the starting point for AL102, the starting point for our interest, is that it has really, really great phase II data, based on the poster that was originally presented at ESMO in the fall of 2023, which was really what sparked our interest. It has a response rate in the mid-60s, 64%, and that compares quite favorably to Ogsiveo from SpringWorks, which had a response rate of 41% in their phase III. So we're looking at potentially a 20% improvement in response rate, so the starting point was really, really strong data. I think there was also a little bit of pattern matching.
Many of my colleagues were involved in the acquisition of Cascadian Therapeutics, and that was a case where you had a late-stage small molecule at a small underfunded company that hadn't been able to properly invest in CMC. And we had this opportunity with a late-stage small molecule, great data from a small company that hadn't been able to invest in CMC. So at heart, we're drug developers. We're, we're focused on antibody-drug conjugates, but, but we are drug developers, and the opportunity to bring on a high-quality late-stage asset was too good to pass up.
Got it. And so right now, there's one therapy that's approved for desmoid tumors. It's a, you know, pipeline or not pipeline, a program from SpringWorks Therapeutics called nirogacestat. How does, you know, AL102 differentiate from nirogacestat?
Yeah. So overall, you know, SpringWorks has done a great job with bringing nirogacestat or Ogsiveo to market. So desmoid tumors are a really painful, debilitating, serious chronic disease. And to this point, there really has not been an effective systemic treatment. So for SpringWorks to take something and get approval and start to introduce patients to the idea of, "Hey, there are these drugs called gamma secretase inhibitors that can bring real benefit to patients," that's great. You know, we really, we think that's phenomenal for patients, and ultimately, that's what we care about. But when you look at what patients are really hoping to get out of these drugs, it's not just about progression-free survival. It is about, "I want my life to get better." So I want my tumor to shrink.
I want potentially to have pain reduced as part of that. I want to, you know, maybe get back range of motion. And so really, we think that patients are looking for reductions in tumor volume, rather than simply looking for progression-free survival. That's where that 64% figure I mentioned earlier comes in, compared to 41% response rate for the SpringWorks drug. We think that is enough of a difference between the two, that it will really establish a new standard of care for desmoid tumors.
I guess, you know, the company has said there's about, what, 5,500-7,000 patients in the U.S. SpringWorks recently, I think, disclosed, at least based on ICD claims data, there could be upwards of up to 10,000 patients. What are your thoughts in terms of market size in the US?
So I think that's first, a very good capture by you. So that 5,500 number, we have been learning more and more about the market for desmoid tumors and about the opportunity. That 5,500 number, that I think you probably got from our presentation, that's a relatively old number. And we've used it because it's conservative. But qualitatively, what we have heard is that now that you have, you know, Ogsiveo on the market, but also our drug available through the phase III trial, patients are really coming out of the woodwork. So this is a chronic condition. There are sort of some treatments for it, but they're not incredibly effective. So, you know, maybe you have someone who was diagnosed 10 years ago. They had a big surgery to remove the tumor. The tumor came back.
They tried an off-label TKI, and ultimately, that didn't work, and it had toxicity, so they had maybe kind of disengaged from treatment, and what we have been told by physicians is that now that there's an exciting systemic treatment, patients are re-engaging, and so it is quite possible that the prevalence pool is larger than people originally believed, you know, as far as the ICD-10 data, I believe the Desmoid Tumor Research Foundation did some good work to get that ICD-10 code established, and so that genuinely is new information that has really only become available quite recently, but it aligns with the more qualitative beliefs we have about this market being larger than anticipated.
The phase II data, in terms of tolerability, with AL102, can you talk a little bit about that and how it, you know, compares with Ogsiveo, if there are any differences there?
Yeah. So the toxicities that we've seen with AL102 are all consistent with the class. We think that you could, you know, maybe point to certain things here and there and say, "Oh, in phase II, Immunome's data looks a little bit better." But the reality is we don't think you can make safety claims or strong claims of superiority on safety off of such a small data set. So for now, our belief is that this is really a story about efficacy and that the side effect profiles are quite similar. You know, they are different drugs, different trials. I'm sure there will be things where we're a little bit better than them, or maybe they're a little bit better than us. But we do see most of the toxicities as being class-driven.
I also think it's worth pointing out that there is a really substantial benefit to patients, and so even with the toxicity profile, you see patients staying on this drug for a very long time. As of the last data cut that we shared from the phase II trial, more than 20 patients were still on the drug, something like 20, at least 23 months, so this has the potential to be something where the toxicities are manageable, the benefits are substantial, and people stay on the drug for a long time.
Right now, you're running the phase III trial called RINGSIDE?
Mm-hmm.
Data are expected in the second half of 2025?
Yes.
What does the data look like in terms of when you unblind the trial? Is the primary endpoint's PFS? So is that what we should be focused on, or are we gonna be focused on response rate, reduction in pain, and other quality-of-life measurements?
Yeah. That's—it's a really good question because PFS is the primary endpoint. Obviously, you need to hit that endpoint. And for cross-product comparison purposes, you know, we think we'll probably be better than the hazard ratio that SpringWorks was able to achieve in their phase III. That said, you know, even if we win on PFS, that is not going to be where we're looking. And that just goes back to the nature of this disease. This is not a metastatic cancer where progression-free survival is really a proxy for overall survival and gets at what patients are trying to solve for. Again, you know, patients are really hoping for a drug that can deliver an improvement to their quality of life and an actual regression of the tumor. So we will definitely be looking at the overall response rate endpoint.
We'll be looking at some of the PRO endpoints. It's not an endpoint, but we'll certainly wanna look at the decrease in tumor volume measured as a percentage, and we think those are what really matter to patients and to physicians.
I guess on positive data, NDA filing would go in shortly after that.
We haven't explicitly guided on NDA timing, but I would say it would be sort of a normal schedule.
What are your plans for commercialization? Are you starting to put a team in place currently, or are there plans to put in a team, you know, going into, you know, the readout and, you know, regulatory filing?
Yeah. We think we're really well-positioned to commercialize this, and that's what our plan is. So we just brought in a head of commercial, someone who's really experienced, played a role in it, et cetera, is at Seagen. And we're starting to lay the groundwork for commercialization. We think it would be a little bit irresponsible to make huge investments before we have top-line data. But there's a lot of work that we can do to make sure we fully understand what our commercialization path will be. You know, as far as what commercialization looks like for a drug like this, it is a relatively small community. Desmoid tumors are rare enough that there are only, you know, maybe 100 places that really treat them in the U.S. Many of the physicians who treat this have some exposure to our drug already through our study.
What we have heard anecdotally from them is that they really, really like our drug. We do feel like it's a very tractable commercialization problem and a huge opportunity that our team is more than capable of handling.
Great. Moving on to, you know, you have a few other pipeline programs. The ROR1 ADC was one that was acquired from Zentalis earlier this year. Talk about, I guess, you know, the thoughts behind acquiring the program. What drove the decision to pursue ROR1 as a target that you wanted to bring in?
Yeah. So I think the starting point for that is ROR1 as a target. So ROR1 is a target that is expressed on both solid and liquid tumors. VelosBio is fairly well-known for having developed a ROR1 ADC that led to them being acquired by Merck for $2.75 billion back in November of 2020, if I recall correctly. And that ADC was able to show some activity, especially in lymphoma, and is still under development by Merck. But what we saw with this program was an ADC where it really felt like it had been designed the right way. I think the temptation when you're designing a new ADC is sort of just take the first antibody you come across or maybe take an antibody that has been optimized as a monoclonal.
And really, we feel you need a look at a panel of antibodies. Don't just look at affinity, and definitely don't just take the best affinity, but consider the affinity, consider things like internalization, obviously consider manufacturability, and so on. And find an antibody that is really right for an ADC. And that's very much the case with this ADC. We also feel like the payload, and I'll talk more about the payload as a standalone item, but we think the payload is really well-suited for ROR1 as a target. As I said, it's expressed in both solid and liquid tumors. And we think that the payload on IM-1021 is very well-suited for solid tumors. It's a proprietary TOPO1 inhibitor that we call HC-74. It is the same drug class as the payload used by Enhertu.
But there's sort of some small tweaks to chemical structure that lead to superior properties for HC-74 when compared to DXd, the Enhertu payload, so we feel like, you know, you take a target with ROR1 where you have seen signs of clinical promise, let's call it, and you take an ADC where it's really been assembled the right way, and we feel like we're going to be able to bring that into phase I dose escalation, both on the solid tumor and on the lymphoma side, and really get to an answer about what the ceiling is for this drug.
As you were evaluating this program, what were the key learnings that you learned from the Merck ROR1 ADC asset in the form of VelosBio? Because, you know, they clearly showed activity in, on the hematologic malignancy side in mantle cell lymphoma, for example, but, you know, on the solid tumor side, they really haven't seen that. So what drove the decision and the confidence that, you know, your program, 1021, can achieve activity in both hematologic malignancies as well as solid tumors? Is it the TOPO1 payload and the differences there, or are there other attributes?
We think that the TOPO1 payload plays a big role in that. So TOPO1 payloads have a lot of great properties. So they, you know, they're quite potent, but you can construct an ADC with a DAR of eight where you have eight different payloads for every antibody. Compared to the Merck drug, which uses MMAE and only has a DAR of four, you can generally dose TOPO1 ADCs at much higher levels, sort of high single digits compared to maybe 1.8 or 2.5 mg/kg for the MMAE ADCs. And in solid tumors, and especially in ROR1 where solid tumor expression, it's there, but it's not extremely high. Being able to deliver that higher dose of drug, we believe, is really important. So I think it's the payload does play a big role there.
IND filing first quarter 2025?
Yeah.
Are there any, you know, items that you need to complete between now and then, or it's pretty much, you know, you're done with everything and you kinda have to put the package together?
Yeah. There's no substantive work that needs to be done. We will meet our guidance.
Got it. And then so phase one would start after IND clearance?
Yeah. Our perspective is that you move quickly with these things. So I don't know that we're going to commit to a specific timeline between IND clearance and first patient in, but we want it to be fast, and we want to get to an answer.
I would assume it's gonna be a dose escalation phase, initially that you start out at. Are the patients gonna be strictly hematologic malignancies, or are you gonna take all comers across both hematologic malignancies as well as solid tumors that are known to express?
Yeah. We'll be doing both hematologic malignancies and solid tumors. We are not requiring a companion diagnostic, so we really think there are opportunities on both sides there.
Got it. And then you talked a little bit about the TOPO1 payload that's unique to Immunome. You know, so I guess from a safety standpoint, how does it differentiate versus, like, a DXd, or other TOPO1 payloads?
So from a safety standpoint, you know, safety is going to be a function both of the payload and of the whole ADC. I think there are things you can do to help mitigate some of the toxicities you see, with something like DXd. We're still doing some of that work, but we can point to things. So if you look at hepatocyte clearance, for instance, HC-74 is cleared from hepatocytes somewhat more quickly than DXd. It's not a huge night-and-day difference, but sort of characteristic by characteristic, whether that's potency or permeability or hepatocyte clearance, we do feel like we have something that is moderately improved over DXd.
Earlier this year, the company made another acquisition from Atreca of about 25 antibodies. How does that play into, you know, this TOPO1 payload and what you're trying to do in terms of generating the next pipeline of ADCs?
Yeah. So that's a really important point because we like HC-74. We think it's important to have a really good payload available. But it's a mistake to jump from that to, "Oh, the most important point of differentiation is payload." We think that the ADC field, there's a lot of good work going on, but it's gotten very, very focused on about 10 targets. And we think that, you know, bringing forward another HER2 ADC, even if you do have the best payload, is your payload so good that it's going to beat out an HER2 in HER2-low breast cancer. At a minimum, it's going to be a very, very big trial to prove that. So we think that the real opportunity is taking a great payload.
You know, you want everything about your ADC to be as good as it possibly can be, and, and then going after a novel target. So you have sort of the ROR1s of the world where there's maybe a couple of companies going after it, but there's no approved incumbent, and there is still the chance to be first in class or, or at least best in class. But then we're, you know, we also want to look at targets including, you know, most of the targets of the antibodies that we acquired from Atreca where really no one's going after it at all.
We think that having the right team in place where you can actually do that target validation work in-house, and take a novel target and really try to understand, you know, there's sort of some things we'll talk about, like expression levels. There are other things that we might talk about a little bit less but are looking at very closely and getting conviction of, "Hey, nobody has brought this target into the clinic, but we've done great work on it." And we think that advancing an ADC against this target into the clinic has a ton of potential. We feel like that's a real differentiator for us.
When do we start to, you know, get a look under the hood in terms of some of the targets that you're evaluating? Would that be like a 2025 timeframe when you start to disclose some of these efforts?
Yeah. So I want to differentiate between disclosing targets and also versus disclosing data about candidates. I mean, I think we would love to be able to share data on candidates quite soon. If you are truly going after novel targets, right, the fact that we're going after ROR1, that's a known target, saying we're going after ROR1 is not particularly problematic. But if you're going after something that nobody else has heard of, and especially with our management team's track record at Seagen, if we go out here and say, "We're going after target X," there will immediately be copycats. So, you know, we want to be able to show what we're doing and, you know, maybe be able to provide some data on new candidates sooner rather than later.
But we're going to be very, very thoughtful about when we actually provide target names because the competitive dynamics there are a real concern.
That's fair. I mean, there's a lot of target crowding in oncology, and so clearly going after first in class, best in class, I mean, would give you a competitive edge.
Yeah.
From the rest of the field. So that definitely makes sense. I know we've got about a minute and a minute and a half left. You know, there's another program that you're developing, FAP radioligand. Talk to us about these efforts because that's also going into an IND, early next year.
Yeah. So that program is still on track for an IND in the first quarter. We think that's a great, really differentiated molecule. So in brief, FAP is a target that is expressed in about 75% of solid tumors, which obviously presents a huge opportunity, but it's a little bit of a tricky target because it's expressed on the fibroblasts in the tumor rather than directly on the cancer cells themselves in general. And so although radioligand therapies are a relatively new modality, we think they're very, very well-suited for something like FAP. And the reason for that comes down to the biology and the physics of it. So if you take a radioisotope, it binds to a cell that expresses FAP, and then it decays.
If you use a beta emitter, and that is what we're using, it can potentially kill four or five cell widths away. So you bind to the fibroblast in the tumor, and then it kills nearby tumor cells. Whereas if you just have an ADC, you know, it might, it may be possible to design an ADC to FAP, but it's going to be very, very challenging. So we feel like it's the right modality for that target.
You feel the beta emitter radioisotope is a much better isotope than, like, an alpha emitter approach?
Yeah. Yeah. It's, I mean, it's certainly true that alpha emitters emit more radiation, but they do not have that same path length, and simply being more potent doesn't guarantee superior therapeutic index, so we do feel like beta emitters for this particular target are the right way to go.
The phase one would also initiate next year at some point post-IND test?
Yes. Yes.
Great. I think we're about out of time. I would like to thank you for, you know, participating and coming to Piper Sandler to share your story.
Thank you.