Foghorn Therapeutics Inc. (FHTX) Earnings Call Transcript & Summary

Greetings, and welcome to the Foghorn Therapeutics' AACR update call. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Karin Hellsvik, Vice President, Investor Relations and Corporate Affairs. Thank you. You may begin.

Thank you. Good afternoon, and good evening, everyone. Welcome to the Foghorn 2024 AACR Conference Call and Webcast. This is Karin Hellsvik, Vice President of Corporate Affairs and Investor Relations at Foghorn. This presentation contains forward-looking statements, which are all statements other than statements of historical facts and include statements concerning the potential outcome from our collaboration agreement with Lilly; our research and development programs, preclinical studies and clinical trials, including our Phase I combination study of FHD-286. Planned Phase I dose escalation study of FHD-909 and status of our selective CBP and selective EP300 degrader program. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our Form 10-K for the year-ended December 31, 2023, as filed with the SEC. Any forward-looking statements made in this presentation speak only as of the date on which it was made. On today's call, I'm joined by our President and CEO, Adrian Gottschalk; Chief Medical Officer; Dr. Alfonso Quintás-Cardama; and Chief Scientific Officer, Dr. Steve Bellon. We have also posted the slides on our website that will be used during this call. The call is being recorded, and a replay will be available on our website. I will now turn the call over to Adrian Gottschalk.

Thanks, Karin. I'm really pleased to be speaking with you today about all of the recent progress here at Foghorn, including important new data for several of our pipeline programs being presented at the 2024 AACR conference. Foghorn was founded 8 years ago around the idea that targeting the system that regulates and orchestrates gene expression with a biology-first approach would have the potential to bring forward a wave of groundbreaking medicines for the treatment of cancer and other diseases. This system is the chromatin regulatory system, and it is responsible for determining which genes are turned on or off. If genes are the blueprints that cells use to make proteins, then the chromatin regulatory system is the architect which determines which blueprints to use. If the architect or the chromatin regulatory system does not function properly, then the wrong blueprints or genes are used at the wrong time. One can see how this system can be relevant in cancer where the wrong genes may be turned on or off at the wrong time and lead to abnormal and uncontrolled growth. At Foghorn, we have built an integrated platform that allows us to study various components of this system, which include remodeling complexes, transcription factors, Helicases and other chromatin binding proteins. We are unique in the systematic biology-first approach that we take. To drug this system, we develop small molecules that include enzymatic inhibitors and targeted protein degraders. We have built significant chemistry capabilities, including highly competitive protein degrader efforts. And as you will hear today, we've been able to achieve impressive selectivity against some very challenging targets for which many in the industry have attempted a drug and not succeeded. The importance of the chromatin regulatory system is significant. In cancer alone, the system is implicated in up to 50% of all tumors, and we believe we could 1 day impact over 2.5 million patients with the therapies that emerge from our platform and pipeline. Today, we will focus on 2 aspects of the chromatin regulatory system that have been part of our AACR presentations. The first of these is an important component of the chromatin regulatory system and a key regulator of gene expression, the BAF chromatin remodeling complex, which has been a focus of Foghorn's early efforts. Historically, the challenge in drugging BAF has been its size and complexing and the fact that most of this complex has no enzymatic activity to target. With insights into the biology of chromatin regulation and the development of proprietary assays, which allow us to integrate chromatin complexes -- interrogate chromatin complexes in the lab in a highly parallel [indiscernible] fashion. We've been able to bring forward 2 very compelling compounds that target this complex, FHD-286 and FHD-909. The second aspect of our focus today will be on 2 other high-value targets, CBP and EP300, both of which are chromatin regulators unrelated to BAF. We have leveraged our platform and expertise to develop highly selective protein degraders of each of these targets, and I'm excited for the team to share our progress with you today. We have both a broad and deep pipeline as shown here. The platform we have built has been very productive as evidenced by the breadth of our pipeline and the strength of the data we've been able to generate to date. Foghorn has a broad array of discovery and development programs ongoing, representing multiple modalities and including several key programs partnered with Lilly. Today, we will walk through recent progress and data for 4 of our programs, including 3 programs where we are presenting data at this week's AACR. 2024 is a potentially transformative year for Foghorn's pipeline as we make key progress and obtain readouts that demonstrate the promise of our first-in-class medicines. On today's call, our Chief Medical Officer, Alfonso, will first review recent progress with our lead program in the clinic, FHD-286. We have multiple lines of evidence that support the development of FHD-286 in combination with decitabine or cytarabine for the treatment of acute myeloid leukemia or AML. We were highly encouraged by the Phase I monotherapy study, which is why we are now pursuing combination development with decitabine, and we anticipate Phase I dose escalation data from the study in the second half of 2024. Alfonso will briefly introduce FHD-909, the selective BRM inhibitor program that is partnered with Lilly and touch on the development status of this program. Following Alfonso, our Chief Scientific Officer, Steve, will discuss the new data at AACR for 3 of our programs, the BRM selective inhibitor and our wholly owned selective CBP degrader and selective EP300 degrader programs. To briefly frame the science with these 3 programs, we are seeking to exploit synthetic lethal relationships where a cancer cell experiences a mutation or loss of 1 protein and becomes highly dependent on a specific related protein for survival. The related protein can be thought of as the Achilles heel for the cancer cell and selective targeting of that protein can lead to death of the cancer cell, yet spare the healthy cells. The biology around the mutations that cause this tumor dependence has become very compelling over the past decade. The challenge for precision medicines that seek to promote synthetic lethality is the ability to selectively target the protein that the tumors are dependent on. This is exactly Foghorn's expertise that has arisen from our platform and why we are so excited to share our progress at AACR across several of our programs. The most advanced of these programs is FHD-909, a BRM select inhibitor, that has emerged as part of our collaboration with Lilly. We are very happy with the progress and profile of this molecule, which speaks to the combined scientific strength of Foghorn and Lilly and the alignment that the company share in bringing forward molecules that meet stringent criteria. As a reminder, we signed a broad collaboration with Lilly over 2 years ago and Lilly selected 909 for clinical development earlier in 2024. At AACR this week, it is our opportunity to share what makes this compound special and what makes us optimistic as we and Lilly head into the clinic targeting BRG1-mutated cancers with 909 and especially non-small cell lung cancer. I will now hand the call over to Alfonso.

Thanks, Adrian. I will highlight the current status and recent progress we have made with FHD-286, our most advanced program in development as well as the near-term clinical plans for FHD-909, our BRM selective inhibitor. I will first discuss 286. By way of background, 286 is a dual inhibitor of BRG1 and BRM also known as SMARCA4 and SMARCA2, which are the catalytics of units of the BAF chromatin remodeling complex. Acute myeloid leukemia cells are known to be highly dependent on the BAF complex for proliferation and maintenance of leukemic phenotype, making the addition of this protein as a promising novel therapeutic strategy for this disease. In preclinical studies, 286 showed significant mutation-agnostic activity across a broad range of primary patient-derived AML samples. When 286 was evaluated as monotherapy in a dose escalation study in patients with relapsed or refractory AML, we frequently observed clear signs of clinical activity manifested as marked decreases in bone marrow blasts and recovery of peripheral blood count, albeit without producing clinical responses as defined by standard response criteria. We have also generated additional preclinical data in AML patient-derived xenograft models for 286 in combination with established AML agents, including decitabine and cytarabine as well as with experimental agents such as BET inhibitors and menin inhibitors. In all cases, the combinations were superior to single-agent 286, both in terms of reducing leukemic burden and prolonging survival. On the basis of these preclinical studies, we initiated a Phase I study of 286 in combination with decitabine for patients with relapsed/refractory AML. The first patient was dosed in the third quarter of 2023. FHD-286 dose escalation is proceeding in 2 separate cohorts, 1 in the presence and 1 in the absence of an Azole Antifungal with a strong CYP3A4 inhibitory activity to assess whether these frequently prescribed drugs in patients with AML impact the exposure and tolerability of 286. Dose escalation is ongoing, and the first clinical data are expected to be available in the second half of this year. It is important to underscore the significant unmet need that continues to characterize AML. While the outcomes of patients with AML have improved over the last decade with the introduction of targeted agents, for a large proportion of patients, mortality remains very high, and survival is measured in months. It is estimated that across the 7 major pharmaceutical markets globally, there are approximately 17,000 relapsed or refractory drug treatable patients, who are not candidates for targeted agents and therefore, lack effective therapies. If confirmed to be active in AML, the combination of 286 and decitabine could afford these patients a much-needed therapeutic option. I look forward to sharing data from this study in the second half of the year. Now I will turn to our FHD-909 program. As Adrian mentioned, FHD-909 is a BRM selective inhibitor that is part of the collaboration with Lilly, and it's heading into the clinic. We expect the IND to be filed this quarter. The initial focus of development will be non-small cell lung cancer, an indication where 10% of tumors harbor BRG1 mutations. From a clinical development perspective, it is worth noting that the therapeutic potential of this compound is linked to its ability to exploit a synthetic lethal relationship set up by the presence of BRG1 mutations. Synthetic lethality is an established precision medicine strategy that has proven safe and effective in cancers with specific mutations. This is probably best exemplified by the approval of PARP inhibitors in multiple solid tumors, such as ovarian, breast and pancreatic cancer, which carry BRCA mutations or other markers of homologous recombination repair deficiency. FHD-909 is the first selective enzymatic inhibitor to enter the clinic with the goal of demonstrating the efficacy of targeting the synthetic lethal interaction that takes place when selectively inhibiting BRM in BRG1-mutating tumors. Cancer genomic studies have shown that BRG1 mutations are found in approximately 5% of human tumors being particularly prevalent in patients with cancer of unknown primary, as well as in those with skin, lung and bladder cancer. Multiple studies have established that BRG1 mutations are associated with the worst prognosis and shorter survival compared to their wild-type counterparts across a wide range of tumor types. Targeting BRG1 mutated tumors with BRM selective inhibitors affords the possibility of addressing their dependency on BRG1 in a targeted manner and the potential of providing much needed treatment for patients who are otherwise Phase IV outcomes. We look forward to sharing the details of the FHD-909 clinical program as we progress through 2024. And with that, I'd like to turn the call over to Steve.

Thanks, Alfonso. I'm pleased to be able to share with you the details of 3 programs in which we are presenting data at this week's AACR conference in San Diego. I will lead with the most advanced of these, which is FHD-909, which as just mentioned, is on track for an IND filing this quarter. The AACR poster presentation is groundbreaking because 909 is the first BRM selective inhibitor to be described in a scientific forum and will be the first of its kind to enter the clinic a few months from now. We are very excited about this program and proud of this achievement. BRM is amongst the top targets in oncology. Many pharma and biotech companies have tried to develop a selective BRM inhibitor over the years, but no one has been successful. We are the first ever together with our partner, Lilly, to bring a selective inhibitor to the clinic. The platform we built over the last 8 years has allowed us to achieve this very exciting result. It would not have been possible without the team we've put together and for the last 2 years, our strong collaboration with Lilly. Preclinical 909's profile is very strong, and we are excited to bring it forward into the clinic. 909 is a highly potent and orally bioavailable allosteric inhibitor of BRM. Crucially, it is approximately 30-fold more selective for BRM compared to BRG1 in a cell line proliferation panel and had minimal inhibitory activity when screened in kinase binding and functional off-target panels. The selectivity is based on the spread of the median IC50 of the BRG1 mutant versus the median IC50 of the wild-type cluster of cells shown here on the left-hand side. In my opinion, this is the most unbiased way of assessing selectivity. At AACR, one of the key pieces of data we are showing is the antitumor activity of 909 in 4 different xenograft models of BRG1 mutated non-small cell lung cancer. What is exciting to me is the magnitude and consistency of the effect that we see across these models. The effects were dose dependent and at the highest doses, we saw either tumor stasis or tumor regression. The H2126 model contains a BRG1 mutation and TP53 mutation, and we observed regression at well-tolerated doses. The A549 model shown on the left panel contains BRG1 mutations as well as a KRAS G12S mutation and is known to be a particularly difficult model to see responses. 909 inhibited tumor growth by 96%. In my experience, this is about as well as any molecule has performed in this particular model. The RERF-LC-AI model shown on the right panel contains a BRG1 and TP53 mutation, and we have achieved almost complete tumor stasis at well-tolerated doses of 909. Lastly, we show very compelling regression in the H1793 model, which has both a BRG1 mutation and 2 TP53 mutations at well-tolerated doses. We believe these results, taken as a whole, underscore the distinct promise of the BRM selective inhibition strategy in tumors with BRG1 mutations. Together with Lilly, we set a high bar for what we would need to see in order to advance a BRM selective inhibitor into clinical development. We are excited by 909's exceptional profile and look forward to it being the next program in Foghorn's pipeline to advance into clinical trials. 909 together with FHD-286 represent 2 key outputs of Foghorn's platform that has initially targeted the BAF complex. Having developed extensive biochemical, biophysics and screening capabilities for BAF, we believe our platform is well suited to drug other chromatin regulatory targets that are complex and have high value. Two such targets are CBP and EP300, where we have new data being presented at AACR. I'll spend a few minutes highlighting these targets and associated selective degrader programs. CBP and EP300 are chromatin regulators that act in normal cells to control protein stability through acetylation. As with BRG1 and BRM, there is an established synthetic lethal relationship between these proteins. In certain cancers, a mutation will develop that will make a tumor dependent on one of these proteins. By selectively targeting the protein that the tumor is dependent on, we hope to establish a novel and effective approach for one or more hard-to-treat cancers. CBP and EP300 are acetyltransferase paralogs and together have been a focus of drug discovery efforts for decades. The challenge has been achieving selectivity. Historically, compounds that hit both CBP and EP300 either as bromodomain inhibitors or is protein degraders, have manifested dose-dependent reduction of platelets in the clinic, limiting their efficacy and therefore, their utility as potential medicines. With our CBP program, we have made strong progress in the design and evaluation of multiple selective CBP degraders. Selective CBP degraders are targeted at tumor cells that have an EP300 loss of function mutation, so that selective CBP degradation affects the tumor cells while sparing the normal cells. In our AACR presentation, we showed a strong antiproliferative effect in EP300 mutant cell lines, representing multiple tumor types, including bladder, gastric and endometrial cancers. Here, I'm showing 3 examples of in vivo models of EP300 mutants. In all 3 cases, our selective CBP degrader showed strong inhibition of tumor growth at well-tolerated doses. The colorectal and bladder examples show very strong inhibition of tumor growth. And in our gastric model, we observe complete regression. Taken as a whole, these strong in vivo results give us confidence in the hypothesis of selectively drugging CBP to address mutant EP300 populations. In addition, we saw no thrombocytopenia or reduction in platelets typically seen with dual EP300 CBP inhibitors and degraders, as shown by the graph here on the left. In the bone marrow staining for platelet-producing megakaryocytes shown here on the right. Based on our strong progress, we are initiating -- we are planning to initiate IND-enabling studies with a CBP degrader by the end of this year, making this program likely to be our next one into the clinic. At the same time, we are seeking to advance novel first-in-class medicines. We are also increasing our optionality regarding delivery of our drugs. Because degrader molecules are sometimes difficult to deliver orally, we are in parallel, investing in formulation technologies that allow us to deliver our medicines once weekly, biweekly, or even once monthly. We have succeeded in formulating one of our selective CBP degrader molecules to degrade CBP over a 2-week period on a single subcutaneous or intramuscular injection. As we optimize this formulation technology, we believe it could offer a very attractive, competitive and convenient form of dosing. Representing the foot side of our CBP program, our approach with EP300 is to design a highly selective EP300 degrader and thus be able to effectively target tumor cells that have become dependent on this protein. This dependency can arise through either mutation of CBP or through other mechanisms that do not involve mutation of either protein. We believe that selective degradation is the key to achieving an optimal efficacy and safety profile with an EP300 degrader. At AACR, we provided our latest data, demonstrating that we are achieving selective degradation of EP300 over CBP in tumor cells and that our EP300 degraders have significant activity in cell lines and in vivo models of prostate cancer and diffuse large B-cell lymphoma or DLBCL. As a further step in a mouse model of VCaP xenograft tumors, degradation of EP300 with Foghorn compounds significantly reduced tumor growth at doses that are not associated with thrombocytopenia or negative effects on megakaryocyte viability. We also showed data demonstrating broad antitumor activity across a range of multiple myeloma and DLBCL cell lines as well as in vivo efficacy in a DLBCL model. To summarize the safety with our EP300 program, we demonstrate that it is well tolerated in an in vivo with no observed decrease in platelet levels and additional mechanistic studies ex vivo shows no effect on megakaryocyte viability at pharmacologically relevant concentrations. We are very pleased with the progress we have seen with these 2 programs and their potential to be first-in-class medicines for patients with tumors harboring either EP300 or CBP mutations. I'm tremendously excited by the progress with our pipeline and the strength of our platform and continuing to deliver highly selective molecules against these unique targets and look forward to updating you on further progress as the year progresses. I would now like to turn the call back to Adrian.

Thanks, Steve. I'm very excited by the progress in our pipeline and the updates we have shared at this year's AACR meeting. As Alfonso shared earlier, we are making great progress with enrollment in our FHD-286 AML combination study and are on track for data in the second half of this year. The unmet need in AML remains high, and I believe FHD-286 may play an important role in the future therapeutic options to treat this disease. With our collaboration partner at Lilly, we are on track to have an IND filing for FHD-909, our selective BRM inhibitor this quarter. The progress of this program to the clinic has been several years in the making and what the field at large has wrestled to accomplish, we are now in a position to bring along with Lilly, the first-ever BRM selective inhibitor into the clinic. With the progress of our selective CBP degrader and selective EP300 degrader, we are further demonstrating that we can selectively drug very challenging cancer targets. We have now done this multiple times, and I believe we will continue to do so in the future, both within our collaboration with Lilly and with other wholly owned targets. We remain on track to deliver 6 INDs over the next 4 years, including our FHD-909 program. 2024 has been and will continue to be an exciting year of progress for us, and I look forward to sharing additional updates on the pipeline as the year goes on. I believe we are uniquely positioned to tackle some of the more challenging targets in cancer, and I'm excited for what we can hopefully 1 day do for the many patients and their families fighting cancer. Thank you for your time and attention today. Operator, you may now open the line for questions.

[Operator Instructions] Our first question comes from the line of Jana Han with TD Cowen.

This is Jana on for Yaron. I have a couple across your programs. For FHD-286, regarding the readout in the second half of this year, can you give us any more color on what we might expect from the data in terms of patient numbers, length of follow-up? And also, what you think kind of the efficacy bar would be for this readout, especially to justify a potential risk of differentiation syndrome? And then secondly, on FHD-909, actually, on FHD-909 and if your BRM selective inhibitor, but you also have a BRM selective degrader with Lilly that's advancing in parallel to late preclinical development. I kind of wanted to understand how this is going to be differentiated from FHD-909 and whether you can give us any timing on the next steps for this program as well as your FHD-909 program?

Great. Thanks. I'm going to -- this is Adrian. I'm going to ask Alfonso to take the first question on 286, which was expectations for the program second half of the year. Alfonso, potential numbers of patients, follow up and the bar for efficacy and then [indiscernible] will come to the 909 program and the BRM selective degrader. So Alfonso.

Yes. So our guidance has been that we will release the data in the second half of the year. The expectation is that -- as well as the desire is that we will, by then, have completed the entire dose escalation schema. And as shown on this slide, we're running effectively 2 separate studies in parallel, 1 in the presence of azoles, 1 in the absence of azoles. And this is important because we want to fully understand the toxicity profile of this combination in the presence and absence of azoles, which are important because they modify as we learned in the Phase I portion of the study in monotherapy. They have a great impact on the exposure to 286. So the expectation is that when we release data, we will release a data set that will contain all of those levels we specified in the dose escalation schema. I'm not going to comment on the number of patients because that varies quite a bit depending on what you see at each dose level. It's very hard to predict. But we will have a full picture of the tolerability of the drug in combination with the size of it. And do you want to comment on bar for efficacy?

Yes. So the types of patients that we're seeing in this combination study, I think they mirror very closely what we saw in the monotherapy component of the study, where the vast majority of them would have been exposed to hypomethylating agents, and, for the most part, Venetoclax, which is very rapidly becoming a standard of care, not just for patients who are unfit to receive intensive therapy, which is the patient population for which the combination has been approved, but also for patients who are much younger. And so we're seeing this paradigm being extended to the vast majority of patients with AML. The outcomes of patients after they fail Venetoclax in combination with a hypomethylating agent, unfortunately, are very poor. The response rates across the series that have been published are typically in the range of 15% to 20%, typically below 20%, but more strikingly, the overall survival of those patients on average is 3 months. And so those are the benchmarks we're working with.

Great. And I think the second question was related to timing for BRM selective, any next steps so we can comment on there. And then anything else we can comment on for the BRM degrader and how that might be differentiated. Steve, if you like those questions, please?

Sure. Yes. So we've guided that we expect to file the IND for 909 this quarter. After that, we'll be working with our partner, Loxo@Lilly to plan out what additional communication there will be going forward. With regard to the degrader, I think now is not the time to go into those details. What I can tell you about our degrader program is that we're quite excited by that effort. And there also will be working with Loxo@Lilly as we move that program forward.

Our next question comes from the line of Vikram Purohit with Morgan Stanley.

This is Gospel on for Vikram. We have 1 question on partnership. So in terms of -- so for the selective CBP and EP300 program, we're wondering now what are you guys thinking in terms of future partnerships?

Sure. Thanks, Gospel. It's Adrian. I'll take that question. I think as we've always said, we remain interested and engaged in business development. I think, decision to partner any asset in our pipeline is always a question of the strategic fit with the potential partner, the capabilities that they bring and obviously, economics that we want to ensure a reward our shareholders and the company for the work and effort we've put into the assets. So on both of those assets, we remain open minded. We know there's interest in both these assets from different companies, just given the state of the field. And so we're going to remain engaged and in conversations along the way. Nothing to commit to at this point in time, but we do see a potential for an asset deal down the road, but we're not going to commit to anything at this point in time.

Our next question comes from the line of Etzer Darout with BMO Capital Markets.

This is Luke Shumway on for Etzer. Just a couple of quick ones. What is the significance of having BRM selectivity over BRG? And then how are you thinking about opportunities beyond lung cancer? Have you had conversations with Lilly on that matter?

Great. Steve, I think you can take both those questions.

Yes. So the importance of selectivity is with regard to tolerability. So the overall thesis here, and this is a classic synthetic lethal relationship, the overall thesis is that in the tumor cell lacking BRG1, we can inhibit BRM, thus killing the tumor cell, whereas in normal cells, they have both the BRM and the BRG1 copies. And with selective inhibition of just BRM, the remaining BRG1 copy can compensate, thus sparing the normal tissue and thus achieving a selectivity window.

Steve, do you want to comment on potential other opportunities for BRG1-mutated cancers and anything we can say about status of conversations with Lilly?

Yes. I think there's tremendous potential with our selective BRM inhibitor. We know that roughly 10% of patients with non-small cell lung cancer harbor a BRG1 mutation, but also beyond lung, BRG1 is mutated in roughly 5% of cancer. And so I think the opportunities are broad and we are working with our partner, Lilly, to evaluate the most productive plan forward, considering these other opportunities as well.

Our next question comes from the line of Paul Choi with Goldman Sachs.

Congratulations on all the progress. I had 2 questions on 909 and then 1 on EP300. My first question on 909 is as we look at the in vivo data, the curves between your low and middle dose tend to overlap. So can you maybe comment on what this means in terms of translating to humans? Does it scale allometrically and just kind of what would the dosing range implications are for people? That's my first question. And second, on 909. Can you maybe just comment on what population would make most sense here? Or is this a post PD-1 and chemo population? And are these patients identified through a standard panel? Or do you have to work through a companion diagnostic here? And then on EP300, can you maybe just comment on what other opportunities may exist? I see that you highlighted prostate and non-Hodgkin's, but just is this potentially expressed in other solid or liquid tumors.

Thanks for the questions, Paul. Sort of split this between Steve and Alfonso. So Steve, on the first part of the 909 question, if you want to comment on the in vivo model, the dosing and anything that we can say as it relates to scaling.

Yes, great question. So in the in vivo models that we showed, you're correct. We don't always get a bigger bang for the buck when we go to the highest dose. That could be because we're maxing out the model or that could be that, that's the extent of the mechanism that we are able to test. I think the only way to really fully evaluate the molecule is to bring it into testing in people, and that's what I'm really excited to learn. As far as the predicted human dose, those are quite complicated calculations that we've obviously performed, and we're quite confident that we can cover the target in our dose escalation -- planned dose escalation study.

And maybe the second part of the question on 909 in terms of the eligible patient population, what those patients might look like, what they may have previously received, Alfonso, if you could just comment on the non-small cell treatment paradigm?

Yes. So as you may understand, we can't really share too many details as to the design of the study out of respect for our colleagues from Lilly, who are now operationalizing the study. No one should be surprised if lung cancer is one of the main indications in the study that we've shown a significant amount of data in that indication. I think it's important to recognize that patients with lung cancer, harboring BRG1 mutations, have been very well studied in terms of their outcomes. These are patients who have very poor outcomes. The overall survival is worse than the average and that encompasses both patients treated with more standard chemotherapeutic agents as well as patients with immune checkpoint inhibition. For a first-in-human study for a dose escalation study, probably doesn't make too much sense to select too much in that patient population. I will expect that going in. But then once the safety profile has been established, it's not unreasonable to think that patients with prior exposure to immune checkpoint inhibition would be a prime patient population going forward.

And then the question on EP300, Steve, about other opportunities in addition to what we've shown today.

Yes. Great question. I think for P300 -- EP300 selective degrader, the opportunities are quite significant. Prostate, as you mentioned, is one, heme is another and then the basket of CBP mutated cancers as well. And we're in the process now of evaluating which of these makes the most sense to be the first route that we take into the clinic. But I think the overall opportunity is quite significant.

Our next question comes from the line of Robert Driscoll with Wedbush.

This is Sam on for Robert. I'm wondering for your CBP and EP300 degraders, have you observed tumor-specific differences in the synthetic lethal interaction? So does the EP300 mutation robustly predict the synthetic lethality with CBP degradation across all tumors equally? Or are there significant differences?

Great question. We do observe subtle differences in the response to different tumor types with our degrader tools. But I think it's a bit premature to extrapolate that -- those differences that we observed into what we might be able to see in the clinic and therefore, what our strategy might be. These are our cell-based models that have their peculiarities. And obviously, as we move forward before we get to the clinic, we'll further evaluate these molecules in PDX models and other opportunities so we can make the best decision we can.

There are no further questions in the queue. I'd like to hand it back to management for closing remarks.

Great. Thank you. I'd like to again just thank everyone for their time and attention today. Thank you to all of our analysts for the questions. We would be happy to follow up if there are further questions post the call. And again, we look forward to keeping you updated as we continue to make progress and exciting times ahead for the company. So thank you, everyone, for your time today.

Thank you.

Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.