Welcome to the Foghorn Pipeline update conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a brief question-and-answer session. As a reminder, this webcast is being recorded today, October 30th, 2025. I will now turn the call over to Karin Hellsvik, Vice President of Investor Relations and Corporate Affairs. Please go ahead. Thank you, everyone, for joining us today. This is Karin Hellsvik, Vice President of Investor Relations and Corporate Affairs for Foghorn. Today's call will primarily focus on our selective ARID1B degrader, as well as updates from Foghorn' s other proprietary programs, our selective CBP and selective EP300 degraders. Before we begin, I will remind you that we will be making forward-looking statements on this call. Please consult our October 30th, 2025, news release for our forward-looking statements disclaimer and our 10-K and other SEC filings for a full understanding of risks in our business. Speaking on the call today, we have Adrian Gottschalk, Foghorn 's President and CEO, who will provide an overview of Foghorn and a perspective on our recent progress. Steven Bellon, Foghorn' s Chief Scientific Officer, who will provide an overview of the progress made on Foghorn' s proprietary pipeline programs, ARID1B, CBP, and EP300, including new data presented at the 8th Annual TP D and Induced Proximity Summit yesterday on ARID1B. Alfonso Quintás- Cardama, Foghorn' s Chief Medical Officer, who will provide a perspective on the clinical opportunity for these programs. We will take questions after the presentation. Christian Humer, our Chief Financial Officer, will join for the Q&A. We have posted the slides on our website that will be used during this call. This call is being recorded, and a replay will be available on our website. I will now turn the call over to Adrian Gottschalk. Thank you, Karin, and thank you to everyone joining us today. I will provide context for today's call with a brief overview of Foghorn's R&D engine and a reminder of our collaboration program with Lilly in clinical development, FHD-909, before handing it over to Steven Alfonso to cover important developments in our wholly owned pipeline. Foghorn was founded around the idea that there was an important set of molecular targets in the chromatin regulatory system that were strongly implicated in cancer but had so far appeared to be undruggable. The chromatin regulatory system controls gene expression. In cancer, this system often goes awry in very specific ways. For a long time, researchers in industry and academia had attempted to drug the chromatin regulatory system, but with very limited success. At Foghorn, we have demonstrated that we can systematically drug the chromatin regulatory system. The chance to have a transformational impact in cancer was very clear. Mutations in the chromatin regulatory system are implicated in up to 50% of tumors. Successful drugs targeting this biology represent multi-billion-dollar opportunities. We have now advanced a portfolio of novel programs targeting hard-to-treat cancers based on our proprietary insights into chromatin biology and protein degradation. Specifically, we have succeeded in bringing forward the first molecules that are drug-like and highly selective for several targets that were previously undruggable. Today, we are on the verge of demonstrating the clinical impact of our innovations with FHD-909, which selectively targets SMARCA2 and is part of our partnership with Lilly. What distinguishes our platform and what has enabled us to make these precision medicine breakthroughs? Importantly, we are focused on novel biology and novel targets. We take a biology-first approach. We have been deliberate in developing a deep mechanistic understanding of the chromatin regulatory system, how the various proteins and complexes interact, and how these interactions can be modulated. We have built an integrated platform that allows us to study the targets in the appropriate biological context and have developed a wide range of small molecule drugging capabilities, which includes targeted protein degradation. We have demonstrated multiple times now that we can selectively drug targets that others have failed to drug. I am excited for Steven Alfonso to provide updates on our progress today. Before we get into the updates on our wholly owned pipeline, I want to say a few words about FHD-909. We are very excited about this program. FHD-909 is a first-in-class, selective oral small molecule inhibitor of SMARCA2 and has the potential to make a difference for patients who have tumors with SMARCA4 mutations. This program is currently enrolling patients in a phase 1 dose escalation trial, and Lilly is responsible for the day-to-day operations. Sites are open in both the United States as well as Japan. The dose escalation portion of the phase 1 includes patients across various histologies, with the requirement that the patient must have a SMARCA4 mutation. We will backfill cohorts as we enter therapeutic range and will enrich for non-small cell lung cancer patients with loss-of-function SMARCA4 mutations. Select backfill cohorts may contain up to 20 patients. At present, the trial is enrolling well, and we anticipate that our collaboration partner, Lilly, will be in a position to determine whether to advance into dose expansion sometime in the first half of 2026. Recognizing that we have not yet hit our maximum tolerated dose, so there may be some error bars around the timing. Beyond FHD-909, our pipeline is broad and advancing. We have made important and critical progress on our wholly owned programs with the goal of building out our pipeline beyond FHD-909 to have potential multiple shots on goal. Yesterday, we reported important breakthroughs for our selective ARID1B program at the 8th Annual Targeted Protein Degradation and Induced Proximity Summit here in Boston. Details of these breakthroughs, together with recent progress on our selective CBP and selective EP300 degrader programs, are the key updates on today's call. We are pleased to see how our capabilities are now enabling us to crack the code on numerous technically challenging but highly promising targets. Before I turn it over to Steven Alfonso to go into the details, I want to summarize the critical takeaways on these exciting programs. Foghorn is the first to publicly show robust degradation of ARID1B. We have made significant progress developing both VHL and cereblon-based degraders. The opportunity with this program is significant as ARID1A mutations, which lead to a dependency on ARID1B, are found in up to 5% of all solid tumors, including but not limited to endometrial, gastric, gastroesophageal junction, bladder, and non-small cell lung cancer. As you will hear shortly, we have achieved significant selectivity and are tracking to in vivo proof of concept in 2026 with this program. Our selective CBP degrader, which has potential in EP300 mutated cancers and ER-positive breast cancer, is on track for non-GLP toxicology studies this quarter with our pre-development candidate, CPPD171, and is tracking to be IND-ready in 2026. We have established a long-acting injectable formulation that allows for subcutaneous dosing weekly or every other week for convenient administration. Importantly, we have overcome the challenge that has plagued dual CBP/EP300 programs, that is, the impact on platelets, and we have demonstrated preclinically that we avoid this tolerability issue. Lastly, our EP300 degrader program has made significant strides, and Steven, Alfonso will go into more detail on the potential of this program in hematological malignancies, specifically multiple myeloma. This is a very compelling program as we have seen clinical proof of concept of this mechanism from a competitor in multiple myeloma, which validates our approach. We believe the highly selective nature of our EP300 degrader will avoid the tolerability issues that are seen, again, with dual CBP/EP300 programs, which may limit the combinability and broad potential in these areas for those programs. We are tracking to IND-enabling studies in 2026 for this program. I will now turn the call over to Steven, Alfonso to take you through the progress in more detail. Thank you, Adrian, and thank you again to everyone joining the call today. I'm excited to tell you about our wholly owned portfolio consisting of selective ARID1B degrader, selective CBP degrader, and selective EP300 degrader programs. Foghorn is focused on the chromatin regulatory system. The important point here is that the structure of chromatin dictates its function. Open chromatin leads to gene expression, and closed or compacted chromatin prevents gene expression. Our targets control gene expression by determining the structure of chromatin. Because many components of the chromatin regulatory system lack enzymatic function, we have been building our protein degrader capabilities to drug these difficult but very important targets since the inception of the company. I've highlighted a few select key areas. Our linker took it is comprised of proprietary chemistry, which has formed the basis of the selective degraders that we are advancing towards the clinic. We place a premium on understanding the mechanism and kinetics of degradation and have put in place a suite of assays to quantitate these properties. Finally, we have invested considerable efforts into formulating our degraders for subcutaneous delivery where oral bioavailability is not tractable, and we have examples of this in the presentation. Foghorn has focused on some of the most relevant and highly mutated genes in cancer. Mutations in these genes, in many cases, set up synthetic lethality or dependency on the sister protein, as is the case for ARID1A, which sets up a synthetic lethal dependency on ARID1B, and of course, mutations in SMARCA4 set up a synthetic lethal relationship with SMARCA2. As you will hear for CBP and EP300, not only do we have synthetic lethal dependencies between the two, but also frank lineage dependency in some tumor types on these genes. I'm excited to now share with you the progress that we've made on our ARID1B degrader program, which was disclosed yesterday at the TP D and Induced Proximity Summit. I'm now going to turn it over to Alfonso to set the clinical context for this program. ARID1A is the most frequently mutated subunit in the BAF chromatin remodeling complex. Mutations resulting in ARID1A loss of function have been shown to accelerate tumor genesis, promote the development of metastases, and induce chemoresistance across multiple human cancers. Approximately 5% of human cancers harbor mutations in the ARID1A gene. As shown on the slide, these mutations are present at high frequency in endometrial, gastric, bladder, and non-small cell lung cancers. This is a very large population of patients whose progression-free survival after failure of frontline therapy is very short, thus representing a high unmet medical need. Let me now turn the call over to Steven. Thanks, Alfonso. Our drugging strategy for addressing the very large ARID1A mutation population is to selectively degrade ARID1B. This approach takes advantage of the synthetic lethal relationship between ARID1A and 1B, where tumor cells are dependent on 1B for survival, but normal cells have their intact copy of ARID1A to compensate for selective degradation of ARID1B. This approach opens up a tolerability window, as demonstrated with the colony formation data shown on the right-hand side of the slide. Here we see that only cells with ARID1A loss are affected by the selective knockout of ARID1B. ARID1B is the most difficult target that I've worked on in my career. ARID1B has no known enzymatic function. The protein is mostly disordered, and it is very similar to ARID1A, making selectivity very challenging. Our approach has been to first find selective binders and then turn the binders into heterobifunctional degraders. I will now share the data and progress with you. Our platform has yielded multiple selective binders to ARID1B, and two example series are shown here. On the left, I show the raw screening data with numerous selective hits shown in the box. On the right, I show the ITC traces for a representative selective molecule from a different series. Using selective ARID1B binders as starting points ensures that selective degradation is built into the resulting degraders, which gives flexibility as we advance our chemistry efforts. We have taken these selective binder starting points and used both the cereblon as well as VHL ligases to preserve optionality. For both approaches, we have been able to progress the series, achieving 80% degradation for the VHL series. This degrader demonstrates robust degradation in several different cell lines with no evidence of a hook effect, shown by the kinetics on the right-hand side of the screen. It's also important to note that degradation occurs at early time points, such as six hours. We have demonstrated that this selective degradation is on mechanism via the ubiquitin proteasome system using various proteasome inhibitors that all rescue degradation, as shown on the right-hand side. In addition, we see no effects on viability across the concentration range shown here. This gives us confidence that our results are not biased by off-target effects on proliferation. In addition to robustly degrading ARID1B, this molecule spares ARID1A and also the BAF complex members, SMARCA2 and SMARCA4. Looking broadly across the entire proteome, we see high selectivity for ARID1B, which highlights the progress we have made with our selective degrader. Other members of the BAF complex, including ARID1A, are shown in red, where you can see no effect. Our chemistry efforts on all three of these programs that I'm speaking to today are guided by structural biology. A nice example of this is shown here with the ternary complex of ARID1B, our degrader, and VHL. One result that emerged from the structure is that the degrader molecule adopts an unexpected conformation in the ternary complex, but not in the binary complex. This seminal insight has paved the way to improved degrader molecules that capitalize on the conformation observed in the ternary complex. I'm gratified to see that the selective degradation that we observed with ARID1B translates into effects on known ARID1B target genes. On the left is treatment with SHRNA, which downregulates the levels of gene A and upregulates the level of gene B. On the right, I show the effect on the same two genes after treatment with our selective ARID1B degrader. The corroboration between the two provides strong evidence that we're on the right track with our selective ARID1B program. I'm extremely excited by the progress that we have made against this difficult target, and I'm looking forward to advancing the program to in vivo proof-of-concept in 2026. Now I would like to transition to our selective CBP degrader program. CBP and EP300 control gene expression by acetylating their targets, leading to open and closed chromatin. Because of the central role they play in controlling gene expression, they've been targets of interest to the industry for decades. The challenge, as shown here, is how to selectively drug these targets, given the high degree of similarity between CBP and EP300. Our approach has been to utilize our platform to design selective protein degraders for each of CBP and EP300. We will focus first on CBP and then on EP300. Before we get into the scientific details, Alfonso will provide clinical context for CBP. I'll now turn the call over to Alfonso. There are two distinct patient populations that could benefit from selective CBP degradation. First, given the synthetic lethal relationship between CBP and its parallel EP300, a selective CBP degrader could target EP300 mutant cancers while sparing normal tissues in which EP300 is intact. This strategy may provide a wider therapeutic window than that observed with dual CBP/EP300 inhibitors, which result in hematological toxicities. The patient population amenable to this approach involves a meaningful proportion of patients with either bladder cancer or gynecological malignancies, such as endometrial, cervical, or ovarian cancer. Second, tumors that exhibit a dependency on CBP function, regardless of EP300 mutational status, could also benefit from CBP targeting. For instance, CBP is a well-known co-activator of the transcriptional activity of the estrogen receptor in breast cancer. This represents a very large patient population, as more than 200,000 cases of estrogen receptor-positive breast cancer are diagnosed every year in the United States. I'll now turn the call back over to Steve. Selective CBP degradation has utility in the context of EP300 mutations, as well as in other contexts of EP300 wild type where a lineage dependence exists on CBP. Here I show three examples of EP300 mutant cancers where a selective CBP degrader demonstrates a range of efficacy between stasis and complete regression. Of particular interest are the two gastric cancer examples, one PDX and the other CDX, that show complete regression of the tumors. Importantly, we are able to achieve efficacy with no significant effect on platelets and sparing of megakaryocytes. I include a dual CBP/EP300 inhibitor clinical stage asset as a positive control, which has a marked effect on platelets and megakaryocytes. From a mechanistic perspective, treating with our selective CBP degrader results in downregulation of genes responsible for cancer cell growth, for example, MYC, which results in G1 arrest and consequently potent antiproliferative activity, as shown on the right-hand side. Exploring dependencies beyond the synthetic lethal EP300 mutation revealed that selective CBP degradation results in reduced expression of ER and its target genes in representative breast cancer models. This downregulation of ER results in cell growth inhibition, as shown by the colony formation data on the right-hand side. Addition of CDK4/6 inhibitors and fulvestrant leads to a dramatic effect on these breast cancer cells, as shown inside the green box on the right-hand of the slide. We are currently in the process of validating the translation of these in vitro colony formation results into the in vivo context. I'm proud of what our platform has enabled us to do with the selective CBP degradation. As shown here, we have a CBP degrader 171, which is our pre-development candidate and demonstrates exceptional selectivity and fast and sustained degradation kinetics. Looking broadly across the proteome, we can see that this is an exquisitely selective degrader and notably does not touch EP300 or any other bromodomain-containing proteins. Recognizing that convenient administration is needed for patients, we have invested significant time in our long-acting formulation technology. We are now able to formulate once a week, if not every other week, or in some cases once monthly, subcutaneous delivery. Here I show our pre-development candidate CBP degrader 171 dosed in two different formulations in the AGS gastric cancer model. The degrader is dosed daily subcutaneously in light blue and dosed once a week subcutaneously in dark blue. The weekly subcutaneous long-acting formulation performs at least as well as the daily dosing arm, achieving complete regression in this model. Degrader CBP 171 has initiated its non-GLP-tox studies this quarter, and we are progressing this forward to be IND ready in 2026. We now move to our selective EP300 degrader program, which has significant potential in hematological malignancies. I will now turn it over to Alfonso again to set the clinical context for this program. The role of EP300 in cancer is complex, acting both as a tumor suppressor and an oncogene, depending on the specific cancer type. In specific cellular context, overexpression of EP300 results in increased cell proliferation and survival across a wide range of hematological and solid malignancies. For the purpose of this presentation, we will focus on the role of EP300 in hematological malignancies, where its dysregulation is linked to the initiation and progression of multiple myeloma and different types of leukemias and lymphomas. The central role of EP300 in these malignancies is further supported by the data presented on this slide, where a selective EP300 degrader induces a profound antiproliferative effect in cell lines representative of the spectrum of hematological malignancies. These data have important therapeutic implications because they suggest that the EP300 lineage dependency observed in multiple myeloma, myeloid malignancies, and aggressive lymphomas could translate in the United States alone into approximately 100,000 patients who could potentially benefit from therapy with a selective EP300 degrader. I will now turn the call over to Steve. As with our selective CBP degrader, here with our selective EP300 degrader, our platform has yielded highly selective and fast protein degraders. EP300 kinetics are shown to be very fast and sustained with the data on the left, and the data on the right show no effect on CBP protein levels over time. Note also the lack of any hook effect with the EP300 degrader. A familiar slide again, as we look across the proteome, we see exquisite selectivity for EP300 over CBP and other bromodomain-containing proteins. Ternary complex structures of VHL and either CBP or EP300 bromodomain proteins reveal the molecular underpinning for the selectivity that we see across both CBP and EP300. In all three panels, I have fixed the VHL proteins in a common orientation for reference so that differences in the bromodomain conformation can be easily compared between the complexes. Focusing then on the bromodomain, one can clearly see that comparing a dual degrader to the respective selective degraders results in markedly different conformations of the bromodomain, which we believe accounts for the selectivity. Structural biology is a strength of ours and an important, often differentiating capability within our protein degrader platform. Mechanistically, we see here that selective EP300 degradation downregulates a set of transcription factors that are the very TFs on which multiple myeloma depends for its survival. On the left, you see MYC, IRF4, and other genes affected across multiple cell lines, as mirrored by the dependency graphs on the right. Furthermore, we demonstrate that selective EP300 degradation induces apoptosis in multiple myeloma cells in vitro. One of the reasons EP300 is a high-priority program for us is the clinical validation that a dual CBP/EP300 inhibitor in a PROTAC has shown compelling results in relapsed refractory multiple myeloma. Here we compare our selective degrader in a preclinical multiple myeloma model where it performs favorably, inducing a complete regression. Of note, we dose the dual CBP/EP300 inhibitor in a PROTAC daily, but we understand that clinically it can only be dosed four days on, three days off, due to tolerability matters. Of note, here again we show that our selective EP300 degrader does not have a significant impact on platelets. We believe the selectivity of our degrader may enable better tolerability in the clinic and ultimately better combinability with other agents in the hematological malignancy area. To preserve maximal optionality for this target, we have pursued both Cereblon and VHL scaffolds. Here I show data with our Cereblon-based degrader in the MM1S model of multiple myeloma in both parental as well as mezigdomide and iberdomide-resistant cell lines. Because Cereblon obviously shares a binding site with the IMiD class drugs, including mezigdomide and iberdomide, we note the decrease in potency of the Cereblon-based scaffolds in the resistance setting due to the aforementioned competition. For this reason, we have focused our EP300 degraders in the context of multiple myeloma using VHL-based ligases. In contrast to the prior slide with Cereblon, here with VHL, we see no loss of potency using the VHL degrader in the resistant context. Furthermore, when our VHL-based EP300 degrader is combined with a standard of care IMiD such as pomalidomide, we demonstrate synergy. This is an important finding because multiple myeloma therapy involves combinations. I hope I have impressed upon you the significant progress we've made with our selective EP300 degrader program. As you see here, we are on the precipice of a pre-development candidate. I show representative molecules A and B along the line of progress we have made to molecule C. I highlight in green the various properties that we have now incorporated within a single molecule, including potency, selectivity, solubility, and clearance. We are tracking towards IND enabling studies in 2026. Overall, as you have heard from us today, we have made significant progress with our wholly owned portfolio. I am very pleased and proud of the progress with our degrader platform and associated programs and look forward to keeping you posted in 2026. I will now turn the call back over to Adrian. Thank you, Steve. As you can tell, we are very enthusiastic about the progress of these programs and the meaningful scientific breakthroughs with these novel targets. We believe the potential with selective ARID1B degrader could be significant given its prevalence in approximately 5% of all solid tumors, and we are aiming for in vivo proof-of-concept in 2026. With CBP, we have demonstrated promising potential in ER-positive breast cancer in addition to EP300 mutated cancers. This program is on track to be IND ready in 2026. Our selective EP300 degrader has significant potential across a range of hematological malignancies, including multiple myeloma, and we believe it is advantaged over dual CBP/EP300 inhibitors that have already demonstrated compelling clinical proof-of-concept. This program is tracking towards IND enabling studies in the next year. We believe all these programs represent important drivers of value inflection for Foghorn. Based on our track record of engineering promising selective therapeutics that target gene regulation, we are poised and positioned to be a durable leader in this area of novel biology. Thank you again to everyone for attending today's call. Operator, you may now open the line for questions. Thank you, Adrian. Please hold for a brief moment while we pull for questions. Our first question comes from Gavin Clark-Gartner at Evercore. Please go ahead, Gavin. Hey, guys. Thanks for putting on this really informative event. I just had two questions on the ARID side. First, could you just help us quantitatively draw the link between SMARCA and ARID since they're both targeting the BAF complex? Based on what you're seeing preclinically, is the level of inhibition or degradation required to see efficacy similar? If it is similar, doesn't that indicate that the SMARCA efficacy that you do see in patients next year has a pretty direct link as to what you could see with ARID? Gavin, thanks. It's Adrian. Appreciate the question. I'm going to let Steve answer that question. Maybe Steve, just to summarize, what do we see as a linkage between the SMARCA programs and ARID and the amount of degradation in this case or inhibition in the case of 999? How does that link to any read-through potentially? Yeah, great question, Gavin. I think quantitating the amount of ARID degradation that we will need to see optimal efficacy, that's a process that is ongoing. It's possible that we see similar behaviors where we need to have really robust degradation in order to see maximal efficacy, but we're still in the process of quantitating that. I think the read-through between the two obviously is appealing since they're both members of the BAF complex, but there are some subtleties. Whereas SMARCA2 is present in all forms of BAF, ARID1A and 1B are not present in the non-canonical forms of BAF. There are subtle differences that make it a little complicated to say that there's going to be complete read-through, but I think that's unavoidable. Yeah, I'll just follow up on that last point. We know that ARID has scaffolding function within the BAF complex, and by degrading it, you could actually disrupt the whole structure. What do we know about the non-enzymatic activity of the BAF complex? I'm trying to get a sense if ARID could actually drive greater efficacy than SMARCA2, which just hits the enzymatic subunit alone. Yeah, that's a really interesting point, Gavin. Yes, the extent to which ARID does contain some scaffolding functions, to that extent, we would expect greater efficacy. We're certainly looking to better characterize and understand that across both biochemical as well as in vitro settings. Awesome. Thanks for the update, guys. Thanks, Gavin. Our next question comes from Steven Ianov at TD Cowen. Please go ahead, Steven. This is Steven Ionov on for Yaron Werber at TD Cowen. Thank you for a very informative presentation. We first had a question about the ongoing FHD-909 study. Any visibility on how much backfilling Lilly is doing and any idea what an initial data readout could contain in terms of efficacy and safety? Given backfilling, how long of follow-up might we expect and for which dose cohorts? Second, it's of course very early, but are we initially thinking of a basket trial with multiple tumor histologies for the CBP degrader program given the multiple tumors you've outlined that are affected similar to the SMARCA2 program? Thank you very much. Great. Thanks, Steven, and Adrian. I'll briefly address the first question on 909. Remind me if I missed any part of it, and then I'll let Alfonso comment on CBP. We're not commenting at this point as a collaboration on status of backfilling other than to say we have the ability as we get into therapeutic range. I think the expectation at some point, once the collaboration has made the decision to move to expansion, assuming that's where we land, is we would communicate high-level efficacy and tolerability certainly to the investment community. What I can say about the study is it's enrolling very well. We have not, as of yet, hit our maximum tolerated dose. We expect that Lilly should be in a position sometime in the first half of 2026, assuming that we continue to dose escalate as we are and assuming that backfilling will happen along the way. We should be in a position to understand whether we're moving to expansion or not. Alfonso, do you want to comment on the putative trial design one could consider for CBP depending on whether you go with EP300 mutant or breast cancer? Yeah, as we mentioned during the talk, there are two patient populations we could target. One is the EP300 mutated patient population. In that sense, I think a basket approach, as you suggested, is probably the right approach because there's a smattering of different histologies that we could target and recruit for. The second bucket, which is even bigger than the first one, is the ER-positive breast. If we decide to go for that indication, I think that will merit its own study. Thank you. Thanks for the question, Steven. Our next question comes from Clara Dong at Jefferies. Please go ahead, Clara. Hi, thanks for taking our question, and I appreciate you putting together this very informative presentation. Within the compiled landscape, we also saw a dual CBP/EP300 inhibitor for multiple myeloma with some initial clinical data. Just curious, compared to the dual inhibition mechanism of action, what's the key differentiation offered by selective degradation? Maybe for those two targets, what kind of advantages does a degrader have over an inhibitor in your view? Thank you. Great. Thank you, Clara and Adrian. I'll repeat the question just to make sure we're clear, and then Steven, Alfonso can tackle this, which is: How do we see selective degradation as differentiating from the dual CBP/EP300 inhibitor, ostensibly an over deb that is being in the clinic? What are the advantages of having selectivity? Maybe secondarily, degradation versus inhibition. Any commentary there? Steve, if you want to start, and Alfonso follow up. Yeah, great question. Thanks. Our strategy is that by selectively degrading these two targets, we can achieve optimal efficacy but avoid effects on the heme compartment, which we demonstrate. As far as efficacy is concerned, we didn't show data with selective binders, but they don't have much effect in the multiple myeloma setting. We need to see a bigger effect in multiple myeloma with a degradation effect, selective degradation effect, and selective binding effect. In other words, our selective degrader approach allows us to have a superior efficacy, which we demonstrated with the multiple myeloma model in the talk, as well as a superior safety by avoiding the effect on heme talk. We think it gives us the best of both worlds, both efficacy and tolerability to selectively degrade these targets. Maybe Alfonso, if you want to comment as an oncologist, obviously given the state of multiple myeloma, combinability, maybe some of the challenges that Steve just mentioned with dual inhibition or targeting of CBP versus selectivity. The main advantages, as Steve alluded to, of selective targeting is the avoidance of myelosuppression. That has profound clinical implications because, as you will know, especially for a first-in-human study, we'll have to go into probably fourth, fifth line at best in multiple myeloma. These are patients that have gone through multiple rounds of chemotherapy and other agents. They have a very limited bone marrow reserve. There's a great need in that space for new mechanisms of action, particularly with known myelosuppressive properties. If we can bring to bear that feature of selective degradation, the avoidance of myelosuppression, I think those patients will benefit significantly from it. The other aspect to it is that not having that element, that myelosuppressive liability, will allow us to combine more safely with other agents. Given the fact that multiple myeloma is a combination game, I think we're going to be able to play along with other agents that are active in that setting. Thank you. Thanks, Clara. Our next question comes from Paul Choi at Goldman Sachs. Please go ahead, Paul. Hi, Adrian and team. Thanks for putting on this session. It's very informative. My first question is on the CBP program. I think you said earlier that you are looking at Q1W, Q2W, and Q4W as possible dosing schedules. Can you comment on whether this involves any changes to the candidate molecule, or is it just more drug and higher cmax that is allowing you to do this? That's a great question. Great question. My second question on the EP300 program in the various hematologies: can you comment on sort of what indication, I guess, would be targeted first potentially here? I think myeloma timelines typically would be longer, whereas AML would be shorter with large B cells sort of falling in between. In terms of your preclinical work, have you done any safety or combination work with existing standards of care in any of these agents? I know you showed some data in resistant lines, but just sort of any combination work there would be informative. Thanks for taking the questions. Yeah. Thanks, Paul, for both those questions. Steve, maybe if you want to take the CBP question. Yep. Alfonso, to discuss sort of initial thoughts on clinical development for EP300. Steve? Great question with respect to the long-acting injectable technology. The strategy is that we can tune the half-life of the subcutaneous injection by adjusting the formulation of the compound without changing the drug itself, the API. Yeah, great. Alfonso? As far as clinical development, I'm sure you noticed that the entire presentation revolves around multiple myeloma, which is, and that's because we're thinking very seriously about advancing the compound in that indication. For a couple of reasons. One is, preclinically, we've seen almost universal sensitivity across cell lines, multiple myeloma cell lines, to the agent. There's a special sensitivity of the indication to this approach. There's a second element, which is the de-risking that has been provided by dual CBP/EP300 inhibition in the clinic. Having that element of de-risking already in place is very important to us. That element is not present in AML, is not present in DLBCL. Those are indications that we are seriously also contemplating as targets for potential clinical development. The main indication right now is multiple myeloma. On combination testing, since a lot of the therapies in multiple myeloma, whether it's CD38 or Revlimid or Pomalyst, what have you, are typically in combination, can you comment on any combination testing you've done preclinically? Yeah, that's all ongoing, and we hope to report out in the future. Yeah, certainly very important there, Paul, that is pending. Okay, great. Thank you. Yeah, thanks for the questions, Paul. Our next question comes from Robert Driscoll at Wedbush. Please go ahead, Robert. Thanks. Hi, guys. Congrats on all the progress here. Real kind of tour de force on ARID1B and the other targets here. Just wondering if you've done any work or maybe others have characterized ARID1A mutations and the effect on function, expression, and so on. Maybe looking forward, I know it's early, but how you're thinking about selecting patients in the clinic there. Thanks. Yeah, thanks, Robert. Good question. Steve, sort of ARID1A effect on function and expression, and then patient selection in the clinic. Alfonso, if you want to speak to that. Steve, to you first. Yeah, the ARID1A mutation status is definitely something that we're digging deep into currently. Basically, yeah, that's incredibly important. We've learned that across other programs, and we are in the process of characterizing the effect of each particular mutation. In terms of patient selection, we have one advantage, one great advantage, which is the fact that ARID1A is customarily being tested in the FDA-approved NGS platform. If you look at the Foundation One panel, you will find ARID1A. We will be able to find and identify patients with ARID1A alterations. I think there's still some characterization to do in terms of class I, class II mutations and the functional importance of each one of these, specifically in ARID1A. For the purpose of patient identification, I think it will be relatively easy. Got it. Maybe sneak one more in. How important do you need that ARID1B degraded to be? I mean, it probably depends on cell lines and so on, but just wondering if you had any thoughts there in terms of the level of degradation required. Great question. That's something we're currently investigating, exactly how much degradation we need for optimal efficacy. I won't speculate. Those experiments are ongoing. Of course, they're helped as we move the program forward. As our tools get better and better, those questions get more and more relevant. Got it. Thank you very much, guys. Thanks, Robert. Our next question comes from Yuan Zhi at B. Riley. Please go ahead, Yuan. Thank you for taking our questions, and thank you for putting out this informative presentation. We got two questions. Maybe we can start with, can you talk about the dynamics of degradation and recovery of ARID1B at DC50? How long does it take to show growth inhibition and cell killing? Steve, do you want to take that question? Yeah. We're still characterizing exactly the dynamics of the cell killing with our degrader molecules. We're still in the process of fully understanding that phenomenon. Got it. For the CBP mutation, is that mutation homogeneous in multiple myeloma patients, or does it have some heterogeneous expression? How will you select patients based on that? For the EP300 program? For EP300, it's a lineage dependency. We're not relying on the presence of these CBP mutations. We've seen sensitivity to the agent across a vast array of cell lines, regardless of CBP mutational status. It's a lineage dependency. We won't have to screen for CBP mutations. Got it. Thank you for taking our questions. Thanks, Yuan. Our next question comes from Silvan Türkcan at Citizens Bank, JMP. Please go ahead, Silvan. Thank you. Thanks for taking my question, and thank you for all these thorough updates here. One question. Thinking about all these large indications that you have coming your way in terms of development and thinking with some IND enabling to be starting next year across the board here, can you just lay out maybe a loose plan around partnerships or your thinking around partnerships or which of these assets you may want to take forward alone to fund these trials? Think about breast cancer here and multiple myelomas that are a little bit larger and heavier. Thank you. Yeah, thanks, Silvan. I'll address that question. Very generally, I would say we're very cognizant that going to very large tumor types is probably best done in a partnership. I think it's always a question of when. We've been very privileged, and I would just say I'm incredibly pleased and highly complimentary of our colleagues at Lilly. They've done a fantastic job with the SMARCA2 program, and specifically as you think about non-small cells. Just to make it specific, I think there's certainly appetite on our end to go into phase one dose escalation and expansion studies, obviously subject to availability of capital and our cost of capital. As we think about registrational type activities down the road, I think having a partner who can execute on clinical studies on a global basis as we think about the various combination agents that are required, certainly if one goes into positive breast, multiple myeloma, and elsewhere, I think those are going to become critical. I tend to be pretty economic sort of minded on this, which is that there's no emotional attachment per se. I think we've got three really great programs that are obviously at slightly different points in time, and we'll just have to see how the story evolves over the next 6- 18 months. Obviously, we want to be very, very disciplined with our capital allocation. Just to be specific about that, we're prioritizing ensuring that we're very well resourced to engage with our collaboration partner, Lilly, on the SMARCA2 program. As we've guided to publicly, we're progressing these programs to IND, and then we'll have to determine whether we partner or are able to get adequate capital to finance a phase one study. More to come on that. Great. Thank you. Maybe could you share some feedback from the presentation at the conference, given I think there's a lot of excitement around ARID1B and you finally being able to develop a degrader here? Was there any feedback? Sure. I'll turn it over to Steve, who obviously presented yesterday. Steve, if there's any high-level comments, I know we received a lot of interesting commentary from colleagues in the industry and other folks who were there given the seminal accomplishment. As far as we know, no one else has been able to achieve this. Steve, maybe you have a few more specific observations or comments you can add. It was quite gratifying that the feedback was quite positive from a number of different people who attended the seminar. People were very curious how we were able to achieve both selective binding as well as selective degradation. They asked questions about the nature of the chemical matter and the specific screens that we ran in order to get the chemical matter. Obviously, we couldn't give a whole lot of clarity there, but I think there was a lot of curiosity about how we were able to achieve what I think a lot of companies have tried and haven't made much progress. That was also very gratifying. Thank you. Congrats again. Thank you. Thanks, Silvan. Great. That concludes today's Q&A session and also today's call. The replay and corresponding slides from today's presentation are available under the investor section of Foghorn' s website. Thank you and enjoy the rest of your day. You may now disconnect.