We're going to go ahead and get started. Thanks, everyone, for joining. I'm Gavin Clark-Gartner, one of the senior biotech analysts here at Evercore ISI, and I'm really happy to be joined with Foghorn Therapeutics CEO Adrian Gottschalk. Thanks so much for joining us, Adrian.
Thanks for having me here.
Absolutely. All right, maybe I'll just turn it over for a quick overview of the company for those who are less familiar with where things stand today.
Sure. So Foghorn is a clinical stage biotech company. We're focused on the chromatin regulatory system, all aspects of how to regulate gene expression that comes from a wide variety of different molecular machines that help decompact chromatin, but also are relevant in directing very specific genetic locations for transcription. We've got a pretty robust pipeline. We've got a. I'm sure we'll talk a little bit about FHD-286, which is currently in a phase one dose escalation study with decitabine in relapsed refractory AML. We've got a really meaningful partnership with Lilly, which was the subject of a deal we did about three years ago. There, one of the marquee programs is FHD-909, which is a selective SMARCA2 inhibitor that's currently in a phase I dose escalation study as well. That just started dosing back in October. Other parts of that collaboration are still confidential.
And then we have our proprietary programs, CBP, EP300, ARID. These are all important targets in chromatin-related biology. These are all synthetic lethal targets, but also in some cases have some frank dependency. And then our platform, which is a mix of biology, drug discovery, and chemistry capabilities. And in particular, I'd highlight our protein degradation efforts given some of the things we're doing on the aforementioned program. So excited to be talking about what we're doing. Maybe I should just add, you know, company is well capitalized into the early part of 2027. And we're excited to continue to progress the pipeline, so.
All right, great overview. We'll dive into FHD-286 since that's the most clinically advanced program and data upcoming pretty soon. Probably a good place to start on this one. Just kind of remind us, trial design and AML. And as you give this update, is this an earlier look or kind of a later look overall at data?
Yeah, sure. So this is a study in combination with decitabine, which people know is a hypomethylating agent. This is in relapsed refractory AML. The vast majority of these patients will have seen venetoclax and azacitidine, so they do have prior HMA experience. There's two arms, if you will, to the study. One is with a strong CYP3A4 inducing azole. The other is with a weak. That was something the FDA had asked us to look at, and we've sort of dose escalated in both arms. The data readout, as it were, will be sort of at the end of the dose escalation study, so we're actually at an inflection and decision point for the FHD-286 program. We set a threshold of something in the 20% range in order to want to continue to develop this in an independent manner.
We've set that range for the following reasons, which is if you look at this patient population, you can achieve sort of single low teen sort of responses in this patient population if you do sort of best care that the physicians can take or administer. And we feel like something in the 20% range is an appropriate threshold for us to want to move it forward independently. We're going to put that in the context of the portfolio, obviously financing environment when we make that decision. And the goal will be to communicate sort of top line and sort of decisions through a press release later this year.
All right, that sounds great. And I'll ask one more question on this program, and I want to turn over to the earlier pipeline. We get a lot of questions from investors. Just thinking about the potential beyond responses, I know the overall survival is pretty poor in this population. Just remind us, what exactly does that look like contemporaneously based on the studies you're able to see? And could we see an OS sign relatively early in this study? Does that inform your decision beyond response rate?
Yeah, sure. So I mean, as you know in cancer, responses are not the only thing that matter. At the end of the day, actually duration and survival is actually what really matters to people. And unfortunately, I have firsthand experience with that in my family. So you're right. In a patient population that's previously received venetoclax and azacitidine, the average overall survival is about two and a half months. So if you are getting CRs, hopefully you're also getting a duration of response that exceeds that two and a half months. That's something that would obviously be important to think about in the totality of the efficacy for this agent.
Awesome. Makes sense. Look forward to hearing that update.
Cool.
Let's go over to FHD-909 on the BRM selective side. Just quickly kind of recap, what exactly is this synthetic lethal relationship? What are you doing with this program?
Yeah, sure. So maybe to just again take a step back to the 50,000 foot level, synthetic lethality, which I'm assuming most people are familiar with, is literally the loss of one gene or a protein that then confers in a cancer cell exquisite dependency on a reciprocal or other gene or protein. In the case of BRM, or I'll refer to it also as SMARCA2 and BRG1, which is the paralog reciprocal protein, which is also referred to as SMARCA4, sorry for the terrible nomenclature here. In the case of a number of different cancers, SMARCA4 is mutated. And this is important. You also need loss of function that's conferred by that mutation. It creates then a dependency on the SMARCA2 or BRM protein. And this has been well documented.
This came out of some of the original work Novartis did and Project DRIVE, certainly being supported by the dependency data coming out of the Broad Institute and Achilles. But there's lots of literature on this showing in various cell lines as well as cell-derived xenografts that if you've lost in these cancers, if you lose that SMARCA4 protein and then you either genetically or in our case now through therapeutically inhibit or knock down that SMARCA2 protein, you can cause tumor shrinkage. In the case of our preclinical data, we've actually shown beautiful tumor stasis and in fact tumor regressions. So we're really excited about this program. Again, just a reminder, this is partnered with Lilly. They are executing the clinical study on this one.
Great. And over the last few months, we've seen data with this target with the same relationship from Prelude, who has a degrader versus which is a little different from your inhibitor. Maybe you could just share your initial thoughts, what was good with the release they've showed, and what room did they leave on the table to potentially improve upon?
Yeah. So look, obviously that's an ongoing phase I study, and our colleagues from Prelude should probably comment more fulsomely if folks have questions there. But I think we were particularly excited by the fact that in an ongoing study where they were continuing to dose escalate, they saw, I think as of their most recent update, two partial responses in esophageal cancer with patients who had SMARCA4 mutations there and two partial responses in non-small cell lung cancer with SMARCA4 mutations. They also saw some stable disease, some other tumor shrinkage. I think we were particularly encouraged by that. Again, obviously we believe we have a better molecule in the form of our inhibitor, and we also have a degrader that's partnered with Lilly. I think our main observation there, and again, time will tell as they continue to dose escalate, is, are they hitting the target hard enough?
Are they getting maximal degradation? I think they've shown some data that suggests that there's still quite some room for further target coverage. And again, they've got a once a week intravenous molecule, so they just may not be able to dose it frequently enough. But again, time will tell as they continue to dose escalate. But we certainly view it as meaningful validation of this synthetic lethal relationship. And I think again, from our vantage point, we've got the better assets both within our inhibitor, which is publicly disclosed, and then with our degrader that's again more confidential at this point.
Yeah. And that's definitely one of the investor questions we've been getting a lot over the last couple of months is what exactly is the exposure response relationship? So it's probably worth saying, you know, from your observations with the biology, with your preclinical experiments and what we can tell based on the emerging clinical data, do you kind of have a target of inhibition that you're aiming for? And how do we think about that, whether that's kind of a steady-state trough value or something else?
Right. So I think Novartis actually has published on this a few years back. I always forget the exact publication. But what I can say based on our empirical data preclinically is you've really got to hit this target, not dissimilar to most oncology targets. You really got to hit this target hard. So in the case of enzymatic inhibition, we're looking for an IC90 sort of target coverage. And you want to be basically above that threshold, ideally for the dosing period or the dosing interval. Again, empirically based on what we've done with degradation, also not dissimilar than other degraders, is you want to probably get to a Dmax of at least 90% or so in that range. Again, you need, in the world of degradation, it's a constant tug of war between the cell resynthesizing that protein and your degrader keeping sort of knocking it.
So you're sort of in that tension. I would say for degraders, it's not only just are you getting to 90%, but it's the speed with which you get there. So the kinetics of these things from a degradation perspective matter. But the totality of what I just said is you want to hit this target hard. You want to keep it constantly suppressed, whether it's an enzymatic inhibitor or constantly degraded, I think in order to achieve the maximum benefit. And we've seen that. We've seen where we've got less potent inhibition or less degradation. You start going from regressions to stasis to TGIs to less effective. So we know we need to hit this really, really hard.
Yeah, that's fair. In thinking about your own ongoing study, which as you noted, Lilly's leading the execution there, maybe just kind of frame trial design, anything specific to call out when we could be seeing some of that initial data?
Yeah, sure. So it's a classic three plus three trial design from an inclusion-exclusion perspective. It is all histologies, but it does require that the individuals coming into the study have a SMARCA4 mutation. I think we'll look ex post after the study as to which of the mutations may be more relevant from a loss of function. But the goal here again is to get through dose escalation so we can get into dose expansion. In terms of guidance to data, we've not actually given an official guidance. My sort of generic answer is it's a phase I dose escalation. These things can take from 12-18 months to run. And again, at the right time with coordination with Lilly, we'll potentially give some updated guidance on that.
I think what we've said again in our investor deck, the intention is to get through dose escalation and then get into expansion where you can envisage a cohort that is purely non-small cell lung cancer, a cohort that maybe have other tumor types, and then obviously combination studies are something that we're going to be probably interested in for the obvious reasons of non-small cell given the standard of care there with PD-1s and chemo and whatnot, so.
Yeah. And have you put out any type of kind of bar for what you're looking for initial response rate thresholds that might be exciting? Maybe what that is in lung cancer versus other tumor types. And then kind of the question that dovetails into that is, how do you think about the response rate translating to PFS or OS benefits with this mechanism? Could there be a longer tail?
Yeah, so we've got several questions in there. Again, I'll try to keep me honest here if I don't get to one of them. We've not given specific guidance per se. I mean, and this is sort of public domain knowledge, obviously, is we know in the second-line setting, docetaxel is used relatively frequently and you get stuff roughly in the 20-ish or so. It seems like everything in cancer is 20%, by the way. I don't know why that is, but speaks to probably the difficulty of treating the diseases. But it's sort of in the 20% range. I think for a dose escalation study, however, remember, you're probably not seeing as many second-line. You're seeing third-, fourth-, maybe even fifth-line patients. So I think it's not appropriate to set that as the bar. What it exactly is, I don't think we're prepared to comment.
That's obviously something that Lilly will be the primary decider on in terms of continuing on within the collaboration. But again, I'd go back to the Prelude data. I'm highly encouraged there with interim data with non-complete target coverage. They're still seeing some meaningful PRs in a very difficult patient population. The one thing I actually should add, which is we know that patients who harbor a SMARCA4 mutation, again, also well documented in the literature, the Kaplan-Meier curves there are very well separated. They have a lower overall survival. So then to your other question, if I'm keeping track on that, look, I think the hope and expectation is that if we can induce meaningful regressions and get meaningful responses per RECIST criteria, that that ideally will lead to overall survival.
And again, responses with no quality of life benefit or extended life is kind of a meaningless measure at the end of the day. I think it's a good proxy initially, but you do want to see survival benefit in cancer patients.
Yeah, and I think it's worth emphasizing one point from the Prelude data. The safety profile was very, very strong, which goes to your point around potential combinations in the future too, looking at docetaxel, pembro, et cetera. What are the theoretical adverse events that could be popping up with the mechanism, especially as you're thinking about combinations? And what are we not seeing today?
Yeah, I mean, I don't want to speculate too much on that. What I can say, which I think again is encouraging when one thinks about selectively targeting BRM or SMARCA2, is it should widen the therapeutic window for targeting this BAF complex. We know from our FHD-286 monotherapy studies, and this has been published through ASH when we gave the AML study, or I don't remember where we published the uveal melanoma data on that study. But for dual inhibition, you see things, and it's more of a tolerability issue. You see fatigue, muscle weakness, some nausea, loss of sense of smell and taste, sort of general malaise, some skin rashes. So I think those are things that we ideally won't see, and again, I'm encouraged by what Prelude saw with their molecule, whatever the selectivity ultimately is with that.
I'm encouraged by it because you didn't see a lot of that. So actually, I agree with your comment. It actually looked like a nice safety profile. Combinations, I don't want to go speculate what you'll see with pembro or chemo or the combination of those or potentially other agents. I think that's why we run the study. But I would expect that there ought to be combinable, so.
Yeah, great. And switching gears, moving over to ARID1B, another component of the BAF complex that you're also targeting with a similar type of relationship to BRM- BRG1. How much do you think the success with BRM reads through to ARID1B in the synthetic lethal relationship? I mean, it's a very interesting target. There could be a little bit of scaffolding or structural importance there with ARIDs. Maybe just kind of frame this target and how to make that translation.
Yeah. So ARID1B, it's actually a very similar story in some ways to the BRM- BRG1, or SMARCA2, SMARCA4 story. So ARID1A, which is the protein that's actually mutated and lost, it's actually amongst the most mutated targets in cancer. It's the most mutated component of this broader remodeling complex. So the goal here, similar to what we've done with SMARCA2, is to find something that can selectively drug the ARID1B protein. It's actually been as hard as the SMARCA2 protein has been, and that's been relatively difficult for the industry. It's actually been even harder to find selective binders to ARID1B. In fact, I don't know of anyone else, at least in the public domain or the conversations we've had, that has actually been able to drug ARID1B selectively. So we've been able to do that.
We've got nanomolar type binders at maybe 100 nanomolar, maybe a little less than that. We've been in the process of converting those into degraders. Don't have anything to say publicly on that other than we hope to be able to disclose something in the next quarter or two on the ability to degrade that protein. I think the patient population here could potentially even be larger than SMARCA2. So it's a range, again, of different histopathologies and different tumor types. Again, you'll need that loss of function of that ARID1A protein. But I think this is a really, really exciting target. I think from my vantage point, there's already been a read-through from the SMARCA2-4 program, both preclinically and what we've done, but obviously with Prelude's data. So I'm personally highly encouraged that going after that target could yield some important breakthroughs in cancer types.
Obviously, they're playing slightly different roles. SMARCA2-4 is the enzymatic function of the BAF complex. The ARID1A, ARID1B are part of the structural. We know that transcription factors bind actually to this BAF complex. I know we'll run short on time to explain that, but ARID1A, ARID1B can play important roles there. There's no question, at least on the preclinical side of this, that it's very relevant. You see these mutations in some cancers. We actually see some of these co-mutations in lung cancer as well. Really excited by that program and hopefully more to say about it in 2025.
Yeah, sounds great. And I think we're out of time. So we'll have to touch on CBP and EP300 at another point in the future.
Next time.
We're going to go ahead and get started. Thanks. Thanks so much for joining us, Adrian.
Thanks for having me here.
Absolutely. All right, maybe I'll just turn it over for a quick overview of the company for those who are less familiar where things stand today.
Sure, so Foghorn is a clinical stage biotech company. We're focused on the chromatin regulatory system, all aspects of how to regulate gene expression that comes from a wide variety of different molecular machines that help decompact chromatin, but also are relevant in directing very specific genetic locations for transcription. We've got a pretty robust pipeline. We've got a. I'm sure we'll talk a little bit about FHD-286, which is currently in a phase one dose escalation study with decitabine in relapsed refractory AML. We've got a really meaningful partnership with Lilly, which was the subject of a deal we did about three years ago. There, one of the marquee programs is FHD-909, which is a selective SMARCA2 inhibitor that's currently in a phase one dose escalation study as well that just started dosing back in October. Other parts of that collaboration are still confidential.
And then we have our proprietary programs, CBP, EP300, ARID. These are all important targets in chromatin-related biology. These are all synthetic lethal targets, but also in some cases have some frank dependency. And then our platform, which is a mix of biology, drug discovery, and chemistry capabilities. And in particular, I'd highlight our protein degradation efforts given some of the things we're doing on the aforementioned program. So excited to be talking about what we're doing. Maybe I should just add, company's well capitalized into the early part of 2027. And we're excited to continue to progress the pipeline, so.
All right, great overview. We'll dive into FHD-286 since that's the most clinically advanced program and data upcoming pretty soon. Probably a good place to start on this one. Just kind of remind us, trial design and AML, and as you give this update, is this an earlier look or kind of a later look overall at data?
Yeah, sure. So this is a study in combination with decitabine, which people know as a hypomethylating agent. This is in relapsed refractory AML. The vast majority of these patients will have seen venetoclax and azacitidine, so they do have prior HMA experience. There's two arms, if you will, to the study. One is with a strong CYP3A4 inducing azole. The other is with a weak. That was something the FDA had asked us to look at, and we've sort of dose escalated in both arms. The data readout, as it were, will be sort of at the end of the dose escalation study, so we're actually at an inflection and decision point for the FHD-286 program. We set a threshold of something in the 20% range in order to want to continue to develop this in an independent manner.
We've set that range for the following reasons, which is if you look at this patient population, you can achieve sort of single low teen sort of responses in this patient population if you do sort of best care that the physicians can take or administer, and we feel like something in the 20% range is an appropriate threshold for us to want to move it forward independently. We're going to put that in the context of the portfolio, obviously, financing environment when we make that decision, and the goal will be to communicate sort of top line and sort of decisions through a press release later this year.
All right, that sounds great. And I'll ask one more question on this program, and I want to turn over to the earlier pipeline where we get a lot of questions from investors. Just thinking about the potential beyond responses, I know the overall survival is pretty poor in this population. Just remind us, what exactly does that look like contemporaneously based on the studies you're able to see? And could we see an OS sign relatively early in this study? Does that inform your decision beyond response rate?
Yeah, sure. So I mean, as you know, in cancer, responses are not the only thing that matter. At the end of the day, actually duration and survival is actually what really matters to people. And unfortunately, I have firsthand experience with that in my family. So you're right. In a patient population that's previously received venetoclax and azacitidine, the average overall survival is about two and a half months. So if you are getting CRs, hopefully you're also getting a duration of response that exceeds that two and a half months. That's something that would obviously be important to think about in the totality of the efficacy for this agent.
Awesome. Makes sense. Look forward to hearing that update.
Cool.
Let's go over to FHD-909 on the BRM selective side. Just quickly kind of recap, what exactly is this synthetic lethal relationship? What are you doing with this program?
Yeah, sure. So maybe to just again take a step back to the 50,000 foot level, synthetic lethality, which I'm assuming most people are familiar with, is literally the loss of one gene or a protein that then confers in a cancer cell that then confers exquisite dependency on a reciprocal or other gene or protein. In the case of BRM, or I'll refer to it also as SMARCA2 and BRG1, which is the paralog reciprocal protein, which is also referred to as SMARCA4, sorry for the terrible nomenclature here. In the case of a number of different cancers, SMARCA4 is mutated. And this is important. You also need loss of function that's conferred by that mutation. It creates then a dependency on the SMARCA2 or BRM protein. And this has been well documented.
This came out of some of the original work Novartis did and Project DRIVE, certainly being supported by the dependency data coming out of the Broad Institute and Achilles. But there's lots of literature on this showing in various cell lines as well as cell-derived xenografts that if you lose that SMARCA4 protein and then you either genetically or in our case now through therapeutically inhibit or knock down that SMARCA2 protein, you can cause tumor shrinkage. In the case of our preclinical data, we've actually shown beautiful tumor stasis and in fact tumor regressions. So we're really excited about this program. Again, just a reminder, this is partnered with Lilly. They are executing the clinical study on this one.
Great. And over the last few months, we've seen data with this target, with the same relationship from Prelude, who has a degrader versus which is a little different from your inhibitor. Maybe you could just share your initial thoughts. What was good with the release they've showed and what room did they leave on the table to potentially improve upon?
Yeah. So look, obviously that's an ongoing phase one study and our colleagues from Prelude should probably comment more fulsomely if folks have questions there. But I think we were particularly excited by the fact that in an ongoing study where they were continuing to dose escalate, they saw, I think as of their most recent update, two partial responses in esophageal cancer with patients who had SMARCA4 mutations there and two partial responses in non-small cell lung cancer with SMARCA4 mutations. They also saw some stable disease, some other tumor shrinkage. I think we were particularly encouraged by that. Again, obviously we believe we have a better molecule in the form of our inhibitor and we also have a degrader that's partnered with Lilly. I think our main observation there, and again, time will tell as they continue to dose escalate, is are they hitting the target hard enough?
Are they getting maximal degradation? I think they've shown some data that suggests that there's still quite some room for further target coverage, and again, they've got a once-a-week intravenous molecule, so they just may not be able to dose it frequently enough. But again, time will tell as they continue to dose escalate. We certainly view it as meaningful validation of this synthetic lethal relationship, and I think again, from our vantage point, we've got the better assets both within our inhibitor, which is publicly disclosed, and then with our degrader that's again more confidential at this point.
Yeah. And that's definitely one of the investor questions we've been getting a lot over the last couple of months is what exactly is the exposure response relationship? So it's probably worth saying from your observations with the biology, with your preclinical experiments and what we can tell based on the emerging clinical data, do you kind of have a target of inhibition that you're aiming for and how do we think about that, whether that's kind of a C trough value or something else?
Right. So I think Novartis actually has published on this a few years back. I always forget the exact publication. But what I can say based on our empirical data preclinically is you've really got to hit this target, not dissimilar to most oncology targets. You really got to hit this target hard. So in the case of enzymatic inhibition, we're looking for an IC90 sort of target coverage. And you want to be basically above that threshold ideally for the dosing period or the dosing interval. Again, empirically based on what we've done with degradation, also not dissimilar than other degraders, is you want to probably get to a Dmax of at least 90% or so in that range. Again, you need, in the world of degradation, it's a constant tug of war between the cell resynthesizing that protein and your degrader keeping sort of knocking it.
So you're sort of in that tension. I would say for degraders, it's not only just are you getting to 90%, but it's the speed with which you get there. So the kinetics of these things from a degradation perspective matter. But the totality of what I just said is you want to hit this target hard. You want to keep it constantly suppressed, whether it's an enzymatic inhibitor or constantly degraded, I think in order to achieve the maximum benefit. And we've seen that. We've seen where we've got less potent inhibition or less degradation. You start going from regressions to stasis to TGIs to less effective. So we know we need to hit this really, really hard.
Yeah, that's fair. And thinking about your own ongoing study, which as you noted, Lilly's leading the execution there, maybe just kind of frame trial design, anything specific to call out when we could be seeing some of that initial data?
Yeah, sure. So it's a classic three plus three trial design from an inclusion-exclusion perspective. It is all histologies, but it does require that the individuals coming into the study have a SMARCA4 mutation. I think we'll look ex post after the study as to which of the mutations may be more relevant from a loss of function. But the goal here again is to get through dose escalation so we can get into dose expansion. In terms of guidance to data, we've not actually given an official guidance. My sort of generic answer is it's a phase one dose escalation. These things can take from 12- 18 months to run. And again, at the right time with coordination with Lilly, we'll potentially give some updated guidance on that.
I think what we've said again in our investor deck, the intention is to get through dose escalation and then get into expansion where you can envisage a cohort that is purely non-small cell lung cancer or a cohort that maybe have other tumor types. And then obviously combination studies are something that we're going to be probably interested in for the obvious reasons of non-small cell given the standard of care there with PD-1s and chemo and whatnot, so.
Yeah. And have you put out any type of kind of bar for what you're looking for for initial response rate thresholds that might be exciting? Maybe what that is in lung cancer versus other tumor types. And then kind of the question that dovetails into that is how do you think about the response rate translating to PFS or OS benefits with this mechanism? Could there be a longer tail?
Yeah. So we've got several questions in there again. I'll try to keep me honest here if I don't get to one of them. We've not given specific guidance per se. I mean, and this is sort of public domain knowledge obviously is we know in the second line setting, docetaxel is used relatively frequently and you get stuff roughly in the 20-ish or so. It seems like everything in cancer is 20% by the way. I don't know why that is, but speaks to probably the difficulty of treating the diseases. But it's sort of in the 20% range. I think for a dose escalation study, however, remember you're probably not seeing as many second line, you're seeing third, fourth, maybe even fifth line patients. So I think it's not appropriate to set that as the bar. What it exactly is, I don't think we're prepared to comment.
That's obviously something that Lilly will be the primary decider on in terms of continuing on within the collaboration. But again, I'd go back to the Prelude data. I'm highly encouraged there with interim data with non-complete target coverage. They're still seeing some meaningful PRs in a very difficult patient population. The one thing I actually should add, which is we know that patients who harbor a SMARCA4 mutation, again, also well documented in the literature, the Kaplan-Meier curves there are very well separated. They have a lower overall survival. So then to your other question, if I'm keeping track on that, look, I think the hope and expectation is that if we can induce meaningful regressions and get meaningful responses per RECIST criteria, that that ideally will lead to overall survival.
Again, responses with no quality of life benefit or extended life is kind of a meaningless measure at the end of the day. I think it's a good proxy initially, but you do want to see survival benefit in cancer patients.
Yeah. And I think it's worth emphasizing one point from the Prelude data. The safety profile was very, very strong, which goes to your point around potential combinations in the future too, looking at docetaxel, pembro, et cetera. What are the theoretical adverse events that could be popping up with the mechanism, especially as you're thinking about combinations and what are we not seeing today?
Yeah. I mean, I don't want to speculate too much on that. What I can say, which I think again is encouraging when one thinks about selectively targeting BRM or SMARCA2, is it should widen the therapeutic window for targeting this BAF complex. We know from our FHD-286 monotherapy studies, and this has been published through ASH when we gave the AML study, or I don't remember where we published the uveal melanoma data on that study. But for dual inhibition, you see things, and it's more of a tolerability issue. You see fatigue, muscle weakness, some nausea, loss of sense of smell and taste, sort of general malaise, some skin rashes. So I think those are things that we're ideally won't see. And again, I'm encouraged by what Prelude saw with their molecule, whatever the selectivity ultimately is with that.
I'm encouraged by it because you didn't see a lot of that. So actually I agree with your comment. It actually looked like a nice safety profile. Combinations, I don't want to go speculate what you'll see with pembro or chemo or the combination of those or potentially other agents. I think that's why we run the study. But I would expect that there ought to be combinable, so.
Yeah. Great. And switching gears, moving over to ARID1B, another component of the BAF complex that you're also targeting with a similar type of relationship to BRM-BRG1. How much do you think the success with BRM reads through to ARID1B in the synthetic lethal relationship? I mean, it's a very interesting target. There could be a little bit of scaffolding or structural importance there with ARIDs. Maybe just kind of frame this target and how to make that translation.
Yeah. So ARID1B, it's actually a very similar story in some ways to the BRM-BRG1 or SMARCA2 SMARCA4 story. So ARID1A, which is the protein that's actually mutated and lost, it's actually amongst the most mutated targets in cancer. It's the most mutated component of this broader remodeling complex. So the goal here, similar to what we've done with SMARCA2, is to find something that can selectively drug the ARID1B protein. It's actually been as hard as the SMARCA2 protein has been, and that's been relatively difficult for the industry. It's actually been even harder to find selective binders to ARID1B. In fact, I don't know of anyone else, at least in the public domain or the conversations we've had, that has actually been able to drug ARID1B selectively. So we've been able to do that.
We've got nanomolar type binders at maybe 100 nanomolar or maybe a little less than that. We've been in the process of converting those into degraders. Don't have anything to say publicly on that other than we hope to be able to disclose something in the next quarter or two on the ability to degrade that protein. I think the patient population here could potentially even be larger than SMARCA2. So it's a range, again, of different histopathologies and different tumor types. Again, you'll need that loss of function of that ARID1A protein. But I think this is a really, really exciting target. I think from my vantage point, there's already been a read-through from the SMARCA2-4 program, both preclinically and what we've done, but obviously with Prelude's data. So I'm personally highly encouraged that going after that target could yield some important breakthroughs in cancer types.
Obviously they're playing slightly different roles. SMARCA2-4 is the enzymatic function of the BAF complex. The ARID1A, ARID1B are part of the structural. We know that transcription factors bind actually to this BAF complex. I know we'll run short on time to explain that, but ARID1A, ARID1B can play important roles there. So there's no question, at least on the preclinical side of this, that it's very relevant. And you see these mutations in some cancers. We actually see some of these co-mutations in lung cancer as well. So really excited by that program and hopefully more to say about it in 2025.
Yeah. Sounds great. And I think we're out of time. So we'll have to touch on CBP and EP300 at another point in the future.
Next time.
But thanks for joining us.
Yeah. Thanks for having me. Pleasure to be here.