Morning, everyone. Day one of the Leerink Partners Global Healthcare Conference. I'm Andrew Berens, senior biotech analyst, head of Targeted Oncology. We're very excited to have with us Galecto, now renamed Damora. Congrats on the press release today.
Thank you.
We have Becker, and we have Sherwin from the company. Thank you for joining us, gentlemen.
Thanks for having us.
Yeah. Thanks, Andy, for having us. Thank you to the banking team at Leerink for their support over the last few weeks as we relaunched the company. It was great to work with them. Before we begin, we'll be making forward-looking statements. Encourage you to check out our filings on our investor page on our website for a full summary of our risk factors. My name is Sherwin Sattarzadeh. I'm the Chief Operating Officer at Damora Therapeutics. I'm joined by Becker Hewes, our Chief Medical Officer. We recently joined in January of this year and worked together for a number of years previously at Blueprint Medicines, where we brought a number of important medicines to market and see an opportunity at Damora to do the same now.
As you mentioned earlier this morning, we renamed the company officially from Galecto to Damora. That was a culmination of several months' worth of work to refocus the company towards our portfolio of mutant CALR directed therapies for myeloproliferative neoplasms. Specifically, we're looking at essential thrombocythemia and myelofibrosis, where we think that the mutant CALR-driven populations in those indications account for about a quarter to over a third of the patient population, and we see that as a potential $5 billion market opportunity in the U.S.. We are building off the efforts of others who recently demonstrated proof of concept in those indications.
We believe that Damora can deliver a best-in-class efficacy, safety, and convenience profile with our differentiated assets, starting with DMR-001, which we're putting into the clinic later this year. Very importantly, we raised just over half a billion dollars in cash from November 2025, the initial private offering and the public offering in February just last month. We're well-capitalized to move quickly to move 001 through proof of concept and quickly get to registration with that asset. Very excited to be at Damora and to be here.
Great. Well, congrats on all the progress. This is for you guys, so anybody has questions, just raise their hand. I obviously have some questions of my own. I'd like to talk about a few things. Number one, the translational risk, which you mentioned. You have another company, Incyte, has a program. I'd like to talk about how confident you are in the CALR pathway in ET and also in myelofibrosis. We'll talk obviously about some of the other therapies in that disease and the opportunity. I'd also like to talk about maybe what you guys are doing differently than what Incyte is where, you know, where you see opportunity, despite the fact that, you know, they've demonstrated proof of concept at this point.
Why don't we start, I guess, with the CALR pathway and what Incyte has shown. I mean, they've presented a couple datasets. I do cover Incyte, so I'm familiar with it.
... for the audience that may not be that familiar with it, why don't you walk us through how confident you are, I guess, about the CALR pathway?
I think the way I think about this is we're entering a new era for the mutant CALR pathway-driven diseases. In ET and MF, this is a time that begins a disease modification endpoint as being the real focus of the therapeutic modalities that are under development, particularly those that address the mutant CALR. What Incyte has shown is that by creating an antibody that binds to the C-terminus of calreticulin, which is the area that binds to MPL or the thrombopoietin receptor, that by disrupting that, you can fundamentally change the course of the disease, and you can decrease the extent to which that transcript or that mutation is in the body. What they've shown over the past year is a reduction...
The least, the lowest lying fruit, I think, Andy, was the platelet count coming down in ET. You know, that's the more mild end of the spectrum. Even in myelofibrosis, they were able to show reduction in spleen volume, reduction in bone marrow fibrosis, reduction in symptoms, and then a reduction in the variant allele frequency, which really represents disease modification. Now, that being said, as you said, it's proof of concept. In order to fully explore and exploit that approach, I think what we need is a more potent, more present, better antibody, and that's what we hope to bring into the clinic later this year.
Let's talk a little bit about that. The two diseases, ET and myelofibrosis, I would say even in myelofibrosis, there seem to be two different classes, Class One and everything else, that had differential responses to what they've shown. What would be the I mean, I think this is important for what you guys are doing. You know, they showed probably the best data, I would argue, in ET, the next best data in Type one, the least compelling data in Type two. What would be the reason that those three diseases would have different responses to the same molecule?
Just to review the biology briefly. Calreticulin has two different types of mutations. There's a large deletion, and that's Type one, and then there's a smaller insertion that's Type two, but both of those lead to the same frame shift, which causes the aberrant biology. Now, Type one is easier to make antibodies against. You might imagine it's a larger deletion or a larger change, so it's easier to make antibodies against it. But there also seems to be something about Type two that makes it difficult for even antibodies that bind well to stop the proliferation or to interrupt that biology.
At Paragon, where we acquired the antibodies, Specifically for DMR-001, what they did was they found a highly avid, very good binder, but then further optimized or selected the 001 candidate based on its ability to stop or reverse the proliferation of the Type two mutation. It retains and improves upon the Type one inhibition that we've seen with the Incyte molecule. If you look at the Incyte data from ASH, you can see that most of the left side of their waterfall plots are the patients that aren't responding very well are the non-Type one patients. That's really an unmet need that remains, and, you know, the FDA recognized this when they granted them Breakthrough Therapy for Type one only, but not Type two.
What we're aiming for is a therapeutic or an antibody where you don't have to worry about the type of mutation, that it has a breadth of activity across Type one and Type two, and we've shown that preclinically, and that it has enough potency to address the full spectrum of disease from ET all the way to more severe MF patients.
Why would ET be easier to treat than even Type one?
The Type one mutation will span both ET and MF.
Okay.
The patients with Type one in both populations are easier to treat than the patients with Type two in each population. ET being a earlier form of the disease where it's not progressed as much, probably hasn't been present as long, is just less aggressive. It's kinda like indolent systemic mastocytosis where you may not need as much firepower in that part of the disease.
Okay. Do you think that by going higher with the Incyte compound, they will be able to address the more difficult to treat diseases?
It's possible. I mean, that's why they're continuing to dose escalate, even above the 2.5 grams that they've dosed so far. What I would say is that when you look at the preclinical data with our antibody and a reference antibody we made based off of Incyte's patent, we being Paragon, the preclinical data clearly shows a difference in affinity and potency for both Type one and Type two, with our antibody being about three times more potent in Type one, about 10 times more potent in Type two. If you think of how that preclinical data is now translating into the clinic, at least for their program, that's where you're seeing that difference in Type one versus Type two efficacy.
If the preclinical data for 001 pans out the way that theirs has in the clinic, we should see that improvement in the Type two efficacy as well. To what Becker was saying, you know, best in class profile here is one where it doesn't matter if you know if you're Type one or Type two. You have one antibody that treats the full spectrum of that mutation.
You mentioned some of the clinical endpoints that they showed some benefit in SVR35, which is a spleen volume reduction, and then anemia benefit. Some of the KOLs that we've talked to in MEDACorp suggested that some of those benefits could just be due to JAK washout. There was an inconsistent protocol. Like, I don't think that they mandated a washout. What are your thoughts about some of what they showed being not CALR related or let's say that drug related, but more of a JAK washout?
Yeah. Jakafi having both wild-type and mutant JAK inhibition, as you know, can cause anemia. I think when the data first came out, a few people suggested that maybe it was just the withdrawal of Jakafi that caused a bump in the hemoglobin. Everyone who treats the patients who's looked at those data, including people that have been on the trial, said that this is faster and a larger increase than they typically see with withdrawal of Jakafi. I think, you know, one of the questions we often get is how will we react to data in the future? I think seeing the persistent elevation in the hemoglobin will be important, which will then prove the point that it wasn't just the removal of the Jakafi.
Right. Okay. The spleen?
You know, with respect to the spleen, I think that what we've seen, particularly when you look at the reduction in the marrow fibrosis. That's visual evidence that what you're doing is getting rid of what makes the spleen large, which is the fibrosis. I think that it's a reasonable theory at first, but as we learn more about what disease modification looks like in this disease, we see that it addresses everything from symptoms to spleen size to the counts.
Yeah. No. That, that's an interesting point. I mean, so to be fair, the doctors that at MEDACorp that were pointing this out were very, very excited about CALR. I mean, they pointed it out in that dataset as being possibility. One was more convinced it was related to the JAK washout than the other, but they both were really excited about CALR, and both said that, you know, it is disease modifying. They also said some interesting things about Jakafi potentially being disease modifying. You know, not necessarily the fact. They actually I think they did suggest that it could cause some decrease in the clonal proliferation. Obviously, it decreases the inflammation, it decreases, you know, the spleen size.
Their definition of disease modification was primarily symptom reduction, and not even as much like what's going on in the bone marrow. I guess how do you guys look at how do you think the right way to look at disease modification is? Go for it.
You know, this is something that we talk about when we're in hematologic malignancies often, and there's a new therapy that really addresses the driver. There's a tradition of looking at things that you can impact. In this case, it's been the spleen size and the symptomatology. Now there are new therapeutics that actually address the root of the disease. We saw this in SM as well, where until you see a reduction in the evidence of the disease or the transcript, in that case it was KIT mutation, in this case it's the VAF for the mutant CALR, you can't really claim that you've reversed the disease.
What people are thinking more about when they get even essential thrombocythemia is preventing a situation where they're behind the eight ball, where you're really trying to get out from under a disease. While I agree that the traditional endpoints are impacted by Jakafi, and they were created for Jakafi, to be fair, but the hitting at the root of the disease is really only gonna be achievable by targeting CALR. You know, to the extent that they mention reduction in the transcript, I don't know whether they were referring to CALR or not, but with Jakafi you'll occasionally see a reduction in V617F, but it's just not as brisk, it's not as consistent as what we're seeing with these CALR antibodies.
Right. Okay. I would think that the ultimate, I mean, obviously survival is important, which Jakafi did have some correlation with, I think, in patients with a certain spleen size if I recall. But the marrow, what's going on in the marrow is gonna be important and, you know, that'll be, I guess, the true definition of disease modification if you can improve that. I guess in terms of some of the limitations of nine four nine, the Incyte molecule, what, you know, what have you guys, you know, what is it about that molecule that limits their ability? I mean, the thing that stood out to me was I think they started at like 50 mg, and they went up to 2.5 g, and I think they're still going higher to try to target.
I mean, I'm not a drug developer. You guys are. Does that seem like a pretty wide range of doses that-
Yeah. Yeah. I think they actually started at 24 milligrams even. You know, a couple reasons for that likely. One is it was a brand-new target, so you know, the regulators were likely a little more conservative with where they would need to start, the dose levels at and be a little bit more, you know, systematic in dose escalating from there. You know, ultimately they've realized that they can, they can continue to dose escalate without running into DLTs. I would say a few things. The potency that they have in both Type one and Type two is, you know, likely why they're continuing to dose escalate, right? They're, they're wanting to see that deeper efficacy, as you pointed out, particularly in the MF population, but even the Type two ET population.
Why not continue to dose escalate if you don't have DLTs? You know, their PK profile is such that they've got a relatively short half-life, right? The volume of drug between the potency and the frequency of administration, because the half-life, they're just putting a lot of drug into the patient in order to try to push the efficacy as far as they can.
You know, for us, given the preclinical profile that we have that we think is advantageous, as well as the much longer half-life, this is where we can start to think about, you know, overcoming some of the limitations that they've run into by having a lower volume, infrequent, you know, starting out every four weeks, but potentially even less frequent than that, and being able to see efficacy at a much earlier time point in our dose escalation part of our study than what they've seen, leveraging our preclinical data. The fact that they've dosed as high as they have without seeing DLTs, we think we can go through dose escalation a little bit faster than they can.
You kind of marry those things together with, you know, lower volume, less frequent, higher potency, the opportunity for a more convenient dosing regimen with an auto-injector versus, you know, infusion every two weeks. You know, if they're moving towards a non-body device, that's great. That's more convenient certainly than IV, but sort of still leaves some room for improvement, obviously, from a convenience standpoint. I think that there's limitations are kinda threefold, and we think we've figured those things out.
Okay. What are the specific attributes? I mean, I'm sure you guys have looked at that antibody.
... you know, its affinity, its disassociation concept, things like that. I mean, is it... You know, what are some of the physical attributes, I guess? The PK I know is short, but what is it that's leading to that specifically?
We've looked at a reference antibody that mirrors their antibody. There are properties beyond just being an antibody, such as the viscosity of the antibody, what happens to it after it's created, that impact the PK beyond anything that we've done to engineer a longer PK. The antibody that we believe is the nine eight nine antibody doesn't seem to have great pharmacologic properties in that it seems to have some aggregation and viscosity issues. These things can lead to an antibody that doesn't lend itself well to subcutaneous delivery, to being in an injector pen, you know, a home device that you can take home and deliver to yourself.
It can impact the PK in the body as well. What we've done is the first thing we did was look for antibodies that didn't possess some of these factors, but also used the YTE modification, which is a change to the Fc portion that decreases the rate at which the antibody is eliminated, and that's led to some very long half-lives in some of the other therapeutics that use this modification. In some of the modeling that we've done to try and understand the doses we can get into an auto-injector, we've assumed very slight increases in half-life, for example, like a twofold increase. With the increase in potency that we have and a twofold increase, we're able to get a number of doses into an auto-injector.
If our half-life is as longer than that, it could be even better than that.
What is the timing now for announcing the candidate and getting the IND filed?
Yeah.
... starting to see data potentially? I know you, I mean, you may not have given formal guidance, but just, theoretically, I guess.
Sure, sure. DMR-001 candidate has been selected. It's going through its standard battery of preclinical development studies. We are manufacturing first-in-human material, and so, you know, all your usual CMC preclinical work en route to getting to IND/CTA filing in mid-year, all continue on track. That's the guidance we've given, is to be filed by mid-year, subsequently in the clinic, you know, thereafter. We actually have our second asset, DMR-002, which we'll be filing the IND and CTA for by the end of the year as well. We've guided towards two clinical proof of concept datasets beginning middle of next year. Dose escalation starting later this year and then reading out at that point.
I wanna point out again that differentiation of all the factors of potency and PK allowing us to start at a dose that we think will be very either in the efficacious range or quickly thereafter in the efficacious range. You know, while the number of patients enrolled by the time we disclose certainly will not be to the same level as Incyte's given how much time they've been in the clinic, but a dataset that will be, you know, in that efficacious range.
What have you learned from them on their dose escalation efforts that will you be able to start at a more aggressive dose that's closer to where you think you'll end up? Like, how many? I mean, most companies, I think, shoot for dose level four or five for activity. Is that kinda where you'll start this one when you eventually start to escalate?
Yeah, maybe I'll just say that it's advantageous to have clinical data at a target with a similar modality to be able to go talk to regulators as to where to start. PK modeling that our team has done that sort of shows where that starting dose would be and where we expect that to, you know, relative to its potency, start to have some clinical activity, is kind of what gives us that confidence to be able to do some of the things that I said. I don't know if you have anything extra you want to add to that.
Yeah. I think that the only other thing to think about is if you have a more potent molecule, each step should bring more efficacy. I mean, I won't speculate whether it's dose three, four or five, but, yeah, we hope to be in the efficacious range very quickly. Yes.
Okay.
A couple of 2 questions, Andy. Just around the subcu, what kind of volume do you expect regardless of the dose level to be a single injection volume? How do you...
Our projections are basically to be a single injection.
Yeah. I mean, we'll see how dose escalation goes, just how high up we get. Sort of the preliminary work thus far is we can concentrate it sufficiently to be in one auto-injector. Again, barring knowing if we want higher doses and what exactly the final dose looks like.
Do you know which auto-injector technology?
Not yet. We just hired our senior vice president of manufacturing, so it's number one on his list.
Feel free to ask as many questions as you want. Anybody can ask questions. We like the questions from the audience. One question I have gotten from an investor before, is just, does targeting CALR, you know, targeting that clonal variant, does it select for more aggressive, potentially select more aggressive disease that's harder to treat? Thoughts on that.
It's a reasonable question given things like osimertinib, where it's gotten to that point in lung cancer. I think that's a different situation, though. The evidence that Incyte has shown, and this is also what we saw in systemic mastocytosis, is that while there are co-mutations that can lead to things like AML, they generally go down as the VAF goes down. There may be an occasional patient who's been sick for so long that they've got a few co-mutations, that will be the patient that might evolve into something, not because of the treatment. It's often just the natural course of their disease as such.
Okay.
I think that's going to be extraordinarily rare, especially since they've shown the reduction in the co-mutations already.
Now, there are other approaches to CALR. I think we should talk about that. You guys have also an alternative approach. Do you think that you can get enough activity with a mAb at the CALR pathway to have enough of a clinical benefit? Do you need to bring in the immune system and your thoughts about that?
You know, what we're committed to is developing a therapies for the full spectrum of patients with calreticulin mutated ET and MF. When Paragon first started these programs, it was at a time where we didn't fully understand what level of firepower you needed in order to tamp down the mutation. We're fortunate enough to have multiple therapies of a spectrum of firepower that we could be investigating in different subsets of the population as there may need to be. Oh-oh-one is our, you know, primary attention at the moment, right? We think that what Incyte has shown with the improvements that we can have with Oh-oh-one, we should be able to treat the vast majority, if not all of the patients that we are talking about.
Having the option for, you know, a little bit more of a firepower approach, is great, but we'll have to see how the data sort of warrants the, you know, the need to do that and in which specific subsets of the population.
I think it's important to remember that like the J&J T-cell engager is not directed at the mutant part of the molecule. Part of the reason we think that they did that is to avoid this difference between Type one and Type two targeting, because if they're hitting a conserved wild type part of the molecule, then it would hit the same across Type one and Type two. We don't have that issue because we found an antibody that hits both. One of the advantages that they were designing this for is obviated by the, by a good targeting antibody to both Type one and Type two.
Where do you think that the TCE would actually fit into the treatment paradigm eventually, then? Let's say the mAb is enough. We should talk also about what the frontline will look like. Is it a combination strategy versus monotherapy? Staying with the TCE for the time being, where do you think that would fit into the treatment paradigm based on what we know so far?
When you think about the toxicity of a TCE, I always think about the worst disease first. What are gonna be the worst patients? They're patients with multiple co-mutations where just hitting CALR is not gonna kill the clones, or patients who just have so much disease burden that they need to be debulked like a leukemic really quickly. Even in that case, I don't think it's a long-term treatment. I think it might get the disease under control, but I still think that a antibody that hits the mutation is gonna be the long-term therapy.
Right.
Again, the data that's been put out by Incyte, you know, very nicely shows the effect that this approach could have, particularly for the ET patients, right? The Type two that are sort of lacking a little bit. Yeah, to Becker's point, like let's see how far we can take it with an antibody that's more potent and see where the unmet need remains.
You have some optionality there?
Exactly.
What about the front line? I know we only have a couple minutes left, but a big question for me, I think, Incyte initially was talking about using alternative endpoints, maybe VAF reduction, you know, kinda like CML and the biomarker. It seems like they've shifted away from that. I don't know how much the interactions they've had with the FDA, but they are basically saying it's SVR35 and TSS scores, which as you mentioned were created... Well, at least the SVR35 was created for Incyte's Jakafi by Incyte. Do you think it's possible to beat Jakafi on those metrics as a monotherapy? If so, what are the potential benefits, if you guys can do it and they can't as a monotherapy, if they need to combine with Jakafi?
Why don't we start with that?
Yeah, I mean, I think, we're at the stage where we have therapies that are actually disease modifying. When you have that evolution to such therapies, there's the need for renewed conversations with regulators about what the right endpoints are when you have an asset like that. We had that experience with AYVAKIT, where we needed to work with the agency on novel endpoints for the ISM registrational trial, right? I think there certainly will be that evolution, but there is a lot of regulatory precedents for those endpoints as well in MF.
The way I see it is, over the next few months, we'll have a view on what their phase three study designs are and what their endpoints are, which will be telling in terms of how the regulators are thinking about that evolution. We have the benefit of a little bit more time to generate our dataset and go back and have those conversations again with the regulators and really see where the evolution of those endpoints could look like. Yeah, I wouldn't... I would kinda leave it at that.
You'll have the benefit that Incyte probably are gonna have those discussions first.
Exactly
see what they, where they come out.
Exactly. What the outcome is kinda lets you reverse engineer a little bit of what the discussions were and what was tried and what wasn't tried.
Do you think that they have enough activity based on what we've seen so far, with their molecule to beat Jakafi in a head-to-head in the front line with SVR35 and TSS50 as the endpoints?
I don't know that they do yet, you know? That's why they're continuing to go up. It kinda depends on the patient population that you select. Maybe in some subsets of MF they could have equivalent effect there. I think that the advantages are gonna be the lack of side effects that are carried by the wild type JAK inhibition. We're gonna have to see what happens with our drug and with higher doses.
Okay.
In ET, I think that there probably is enough firepower to, you know, go up against anything there 'cause you're really shutting it down in a, in a milder disease population, so.
Okay. If, if you guys, your more potent antibody, more optimized, I guess, for the indication, there's obviously advantages to that, you know, have to combine with Jakafi, what are the obvious advantages other than, you know, not having to run a combination trial?
You mean to the patient or-
Yeah, to the patients and commercially, I guess. Like what, you know, for the physicians.
I would say that, I mean, we've already talked about the potency and half-life differentiation, so I think there's certainly, that's some of the differentiated profile. What we're focused on is a development program that ultimately when it reads out, has a differentiated label from what they're doing. Learnings from our dataset, learning of what they're doing is gonna certainly inform that. What I would say is that, what we learned with AYVAKIT was there was a view prior to its approval that it would only be used in more severe patients, whether that be advanced SM or some of the more severe ISM patients. Once it was in the available therapy and people started using, got comfortable with it opened up a much broader set of eligible patients.
I think there's an opportunity here as well to really just redefine who the patients are that could benefit from it. If there's 70% of patients taking cytoreductive therapy with ET, I would start there and say that that's the broader population that we could be targeting.
I mean, the other thing that came across in the MEDACorp docs was they do believe disease modification should be used early.
Yeah
... you know, not wait till the patients... even in ET, which is, you know, a lot of patients are watch and wait now, but they-
Yeah
... they did suggest that they would stop you know, they would be more aggressive in treating...
Yeah
... less watch and wait in that setting. In MF they don't watch and wait now.
Yeah. Very similar to ISM, right? They're fine. They're on what they're on. They're balanced. They're well taken care of, but you're not affecting the underlying disease.
I mean, Andy, you know, you've treated patients. You know how they think. People wanna not have the anxiety of worrying about progression of their disease. They wanna forget that they're sick, and, you know, an injection that's spread out even potentially longer than once a month, and then you don't think about it anymore, you don't have the side effects of Jakafi, you know, you gotta ask yourself, what would you choose?
Right. In terms of if you can get in the front line as a monotherapy, there are a fair number of patients that are JAK ineligible, right? I think the number's somewhere around 20%. You guys could target that.
... that group.
At least.
Yeah.
Okay. All right. Well, I think we're over time. Congrats on all the progress. Let me just see if there's any questions in the room. Any questions from anyone? All right.
I think-
Thank you for joining us. Congrats on the progress. Congrats on the name change. I guess the next announcement will be a CEO. Are you guys close to that announcement?
The board is focused on that. We are all prioritizing that, and, you know, as soon as we have news, we'll share that. You know, the focus has certainly been on building out the organization, and there's a lot of interested folks, from our prior networks. There's a number of companies that have recently gone through acquisitions. The level of interest in joining Damora has been pretty high.
Great. Well, thanks.