Good morning and 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, April 29, 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, and welcome to Foghorn's webcast from the 2025 AACR annual meeting. This is Karin Hellsvik, Vice President of Investor Relations and Corporate Affairs for Foghorn. Today's call will focus on new preclinical data on how Foghorn is targeting SMARCA2-dependent tumors with FHD-909, also known by the Lilly designation LY4050784, as well as data on additional first-in-class anti-cancer programs that we're advancing towards the clinic. Before we begin, I will remind you that we will be making forward-looking statements on this call. Please consult our April 15, 2025 press 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 FHD-909 and Foghorn.
Alfonso Quintas-Cardama, Foghorn's Chief Medical Officer, and Steve Bellon, Foghorn's Chief Scientific Officer, who will discuss in detail the data for FHD909 at AACR, as well as the status update on our clinical program. Additionally, Steve will review Foghorn's proprietary pipeline programs, including new data being presented at AACR. We will take questions after the presentation. Christian Humer, our Chief Financial Officer, will join for that part. 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.
Thank you, Karin, and thank you to everyone joining us this morning to hear about our updates from this year's AACR meeting. I will kick us off by providing a perspective on FHD909 and why we think this has the potential to make a dramatic difference for patients who have tumors with SMARCA4 mutations. FHD909 is the first molecule of its kind. It is a highly selective oral inhibitor of SMARCA2. Given the prevalence and clinical severity associated with SMARCA4 mutations across major tumor types, FHD909 has multibillion-dollar potential. Our initial emphasis is addressing the major unmet medical need for patients with SMARCA4 mutations in non-small cell lung cancer. SMARCA4-mutated cancers are dependent on SMARCA2 for survival, and that is what makes SMARCA2 inhibition, if it can be achieved selectively, such a promising strategy.
There is a strong synthetic-lethal relationship between SMARCA2 and SMARCA4, and recognition of this relationship has resulted in SMARCA2 becoming an important and valuable target to industry for the treatment of cancer. We are at the forefront in this area of oncology drug development, and our confidence in FHD909's potential is supported by an array of in vivo data that shows significant anti-tumor activity and tumor regressions. One of the most important aspects of FHD909 and our efforts around SMARCA2 is the partnership we have with Eli Lilly. We entered into our collaboration with them in December of 2021, and it still stands as one of the largest deals signed for preclinical programs in the history of the industry, with a significant upfront payment and meaningful downstream participation for Foghorn.
Lilly is one of the leading oncology companies in the world, and we are proud of how we are delivering in this collaboration. As a reminder, Lilly selected FHD909 as a drug candidate in 2024, and we are aligned with Lilly on how to establish proof of concept and how to maximize the benefit to patients. You saw at AACR last year, and you will see in new data this year how the collaboration has undertaken extensive evaluation of FHD909 across a range of models of SMARCA4-mutated cancers in combination with chemotherapy, KRAS inhibitors, and the immune checkpoint inhibitor pembrolizumab. These combination data are informing our future development plans. There is even more that we are working on with Lilly as part of our broad collaboration. FHD909 is the most advanced, and we are excited to talk about it today.
I will now turn it over to Alfonso and Steve to talk about the new AACR data with FHD909 and to provide a status update on where we are in the clinic.
Thanks, Adrian. As a former practicing oncologist and drug developer in academia as well as in industry, I cannot think of many targets in oncology as attractive as SMARCA2. This is both because of the high prevalence of SMARCA4 mutations in human cancer and because of the sound biological rationale for selectively targeting SMARCA2 given the synthetic-lethal interaction with its parallel, SMARCA4. It must be noted that multiple efforts by many companies to develop SMARCA2 inhibitors have been hindered by the difficult challenge of achieving selectivity over SMARCA4. For that reason, we believe FHD909 is well-positioned to become a transformative cancer therapeutic, and Foghorn and Lilly are working to turn this potential into a reality. This chart highlights the potential of SMARCA4 as a cancer target.
Large genomic studies have identified SMARCA4 mutations in approximately 5% of all human cancers, with cancer of unknown primary, skin, lung, bladder, and endometrial cancers having the highest prevalence. In non-small cell lung cancer, which is a key cancer histology for the early development of FHD909, about 10% of cases harbor SMARCA4 mutations. Multiple studies have shown that SMARCA4 mutations are associated with lower response rates to standard therapy and shorter survival among patients with non-small cell lung cancer. The Kaplan-Meier plot on the left-hand side of the slide depicts the impact of SMARCA4 mutations on the survival of patients with non-small cell lung cancer. The median overall survival of patients with SMARCA4 mutations from the time of diagnosis of metastatic disease is eight months, whereas the median overall survival of the wild-type counterpart is 15 months.
SMARCA4 mutations rarely overlap with other targetable oncogenic drivers in lung cancer, with the exception of KRAS, as illustrated on the right-hand side of the slide. This is important because patients with non-small cell lung cancer and mutations in SMARCA4 and KRAS have dismal response rates and shorter progression-free survival and overall survival compared to patients with KRAS-mutated non-small cell lung cancer but with wild-type SMARCA4 alleles. This data underscored the poor prognosis of patients with non-small cell lung cancer expressing SMARCA4 mutations with or without the presence of other oncogenic mutations. Moreover, these data highlight the urgent need to develop novel agents to improve the outcomes of patients whose prognosis is particularly poor at present. I will now turn it over to Steve.
Thanks, Alfonso. I would like to spend a moment discussing the concept of synthetic lethality and the relationship of SMARCA2 to SMARCA4. SMARCA2 and SMARCA4 are paralogs, highly similar and closely related proteins, and they play a key role in gene regulation as part of the BAF chromatin remodeling complex. Going left to right on the slide, in healthy cells with no SMARCA4 mutations, either SMARCA2 or SMARCA4 functions as the ATPase subunit of the BAF complex that regulates gene expression. It is now well known that in certain cancer cells, SMARCA4 is mutated and/or nonfunctional, which makes them reliant on SMARCA2 for their survival. SMARCA2 and SMARCA4 have a synthetic-lethal relationship, which means if they both go down, the cell will die. For cancer cells that are dependent on SMARCA2, the strategy is therefore to inhibit this protein, causing the death of the cancer cell.
Healthy cells are spared because they can use their intact SMARCA4 to compensate for SMARCA2 inhibition. Last year at AACR, we presented data on the selectivity of FHD909, and that is reprised on slide 11. Based on a broad panel of cell lines, we see that FHD909 is more than 30-fold more selective for SMARCA2 compared to SMARCA4. This is further supported in vivo data that show that FHD909 has no effect in lung cancer models with wild-type SMARCA4. This is compelling in vivo validation of the synthetic-lethal relationship between SMARCA2 and SMARCA4. As shown previously, FHD909 has activity as monotherapy in a range of models of SMARCA4-mutated non-small cell lung cancer. The consistency of activity across models is very encouraging, as is the fact that we were able to observe tumor regression in multiple models.
The A549 model, in particular, is widely used in the field to profile the potential of new medicines in non-small cell lung cancer. It is known to be a high-bar model of SMARCA4-mutant lung cancer. In this model, FHD909 significantly inhibited tumor growth. This is about as well as any molecule has performed in this model that we are aware of. We are confident, based on the biological rationale and on our in vivo monotherapy results, that FHD909 will show clinical activity as a single agent. We and Lilly are also mindful of the non-small cell lung cancer treatment landscape. The vast majority of patients receive combination treatment wherever they are in the treatment cycle. SMARCA4 mutations are common in non-small cell lung cancer, whether in first, second, or third-line patients. We ultimately expect FHD909 to be used across these settings to address patients with SMARCA4 mutations.
Given the propensity of physicians to use combination approaches, it is important for us to define the potential added benefit of using FHD909 in combination with many of the leading non-small cell lung cancer therapies, including and especially pembrolizumab and platinum-based combinations. The slides that follow provide detailed data, as presented yesterday at AACR, on the activity of FHD909 in combination with other agents in non-small cell lung cancer in different xenograft models. This includes combination data with chemotherapies, combination data with experimental KRAS inhibitors, and combinations with pembrolizumab. What continues to be remarkable is the magnitude and consistency of 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. Shown on slide 14 are results from the A549 model, which happens to have both SMARCA4 and KRAS mutations.
In this model, FHD909 in combination with cisplatin plus pemetrexed demonstrate clear tumor regression. Slide 15 shows the replica model of mutant non-small cell lung cancer, where we combine FHD909 with cisplatin and paclitaxel. As with the A549 model shown on the previous slide, we observe tumor regression. We observe a greater effect on tumor growth with this combination than with either chemotherapy or FHD909 alone. This further increases our conviction in FHD909. We evaluated the combination effect of FHD909 in several different SMARCA4 mutant tumor types that, in addition, harbor various KRAS mutations. We are especially interested in these combinations because patients with co-occurring SMARCA4 and KRAS mutations have even worse outcomes. Evaluated in vitro, we see synergy between FHD909 and KRAS G12C, G12D, and pan-KRAS inhibitors in lung, pancreas, and colon cancer models. The breadth of response across this range of tumor types and combination partners is encouraging.
The in vitro effects shown on the previous slide translate nicely into the in vivo models on the next two slides. First, FHD909 was evaluated in combination with olomorasib, which is a KRAS G12C selective inhibitor, in the NCI- H2030 model, which contains both SMARCA4 and KRAS G12C mutations. The resulting complete tumor regression from the combination is compelling. Here we show striking combination data in the A549 model, which contains both SMARCA4 and KRAS G12S mutations. The combination of FHD909 with the experimental pan-KRAS inhibitor LY4066434 shows tumor regression. Given the poor clinical prognosis for patients with these co-occurring mutations, seeing the level of anti-tumor activity in xenograft models is highly encouraging. Overall, the multiple observations of tumor regression in the A549 model with different combinations, both with chemotherapy and also with KRAS inhibitors, is gratifying, considering the fact that this is a high-bar model.
One of the most commonly used agents in non-small cell lung cancer is pembrolizumab, and it's especially important as a first-line therapy. These results are for the A549 non-small cell lung cancer xenograft grown in a humanized mouse model. Interestingly, in this model, pembrolizumab alone has no effect on tumor growth. When 40 mg/kg of FHD909 is combined with 10 mg/kg of pembrolizumab, the effect is profound, and you see tumor regression. These are highly encouraging data and make us optimistic about what we may see from such a combination in the clinic. I will now turn it back to Alfonso.
Our partner, Lilly, initiated a phase one clinical trial of FHD909 last year, and the design of this study is shown on slide 20. The study has two phases: dose escalation and dose expansion. The dose escalation portion of the study is ongoing, and enrolling patients with any solid tumor harboring SMARCA4 alterations will be treated with FHD909 orally in 28-day cycles. Upon completion of the dose escalation part of the study, two independent expansion cohorts will enroll patients with either non-small cell lung cancer or with other advanced solid tumors harboring eligible SMARCA4 alterations. The study may backfill select phase 1a dose cohorts. This slide shows a simplified version of the current therapeutic landscape in non-small cell lung cancer by line of therapy.
Newly diagnosed patients with non-small cell lung cancer and no actionable mutations frequently receive immune checkpoint inhibition with agents such as pembrolizumab, either alone or in combination with other immune checkpoint inhibitors, or more frequently with standard chemotherapeutic agents. For relapsing patients, available options typically involve the use of targeted agents, chemotherapy, anti-angiogenic agents, or combinations thereof. Based on the preclinical activity Steve just described, the frequency of SMARCA4 alterations in non-small cell lung cancer and their negative prognostic implications, FHD909 has the potential to be developed in combination regimens with standard agents in non-small cell lung cancer, such as immune checkpoint inhibitors, KRAS inhibitors, and/or chemotherapeutic agents. We believe FHD909 could become a standard front-line therapy for patients with non-small cell lung cancer whose tumors harbor SMARCA4 mutations.
Going back to where we started the discussion, what drives us to accelerate the development of FHD909 is that non-small cell lung cancer patients with a SMARCA4 mutation have lower survival rates than patients with SMARCA4 wild type. Also, because a major reason for failing immune checkpoint inhibitor therapy in lung cancer is due to the acquisition of SMARCA4 mutations. With FHD909, we have the opportunity to change the natural history of SMARCA4-mutated non-small cell lung cancer and therefore the possibility to improve the lives of patients with such a diagnosis. We are currently enrolling patients in the monotherapy dose-finding portion of the study. Along with our colleagues at Lilly, we are designing front-line combination studies in anticipation of success of the dose escalation study. We look forward to keeping you updated as the study progresses. With that, I will now turn it back over to Steve.
We will go next to the discussion of our proprietary pipeline programs beyond FHD909. We have three programs that are advancing toward the clinic: our selective CBP degrader program, our selective EP300 degrader program, and our selective ARID1B degrader program. The discovery of FHD909, as well as the rest of our pipeline, has come from our platform, which is built around a deep and proprietary understanding of the chromatin regulatory system. CBP and EP300 are chromatin regulators that act in normal cells to control protein stability through acetylation. As with SMARCA2 and SMARCA4, 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 as protein degraders, have manifested dose-dependent reduction of platelets, requiring dose holidays and limiting their efficacy and therefore their utility as potential medicines. Our strategy for CBP and EP300 is to develop selective degraders for each protein target and thereby preserve meaningful efficacy but avoid the heme toxicity that has plagued dual-drugging approaches. That is exactly what we have accomplished. We have a selective CBP program and a selective separate EP300 program, each of which we are excited about. I will start the review of our pipeline programs with CBP.
These are results we have reported previously, which show the impact of selective CBP degradation in models of lung cancer, bladder cancer, and gastric cancer. The CBP degrader in these in vivo studies is 1,000-fold selective for CBP. Our degrader platform has allowed us to generate very selective degraders of CBP that have impressive single-agent activity but avoid negative effects on platelets. We have invested significant efforts in order to deliver our VHL-based degraders with intermittent subcutaneous dosing. The bladder xenograft study shown on the left-hand side of the slide compares the efficacy of a CBP selective degrader delivered daily in green and only once for the entire efficacy model shown in dark blue. Clearly, the efficacy obtained with a single injection is at least as efficacious as the daily dosing arm of the experiment.
Also note that end-of-study measurements show no effect on platelet levels for either mode of dosing. We are excited about the potential of this long-acting injectable formulation technology to allow once weekly, every other week, or even monthly subcutaneous injections in the clinic. As we advance our CBP selective degrader program toward the clinic, this is how we will dose our drug. We are excited about new in vitro data with our CBP degrader presented yesterday. Abemaciclib, a CDK4/6 inhibitor in combination with fulvestrant and estrogen receptor antagonist, is standard of care for advanced breast cancer. The images on the left show the dose-dependent activity of the CDK4/6 fulvestrant combination, and the images on the right show the impact of adding our selective CBP degrader to that combination.
First, comparison of the two yellow circles demonstrates single-agent activity of the CBP selective degrader where no CDK inhibitor or fulvestrant are included. Adding in the CDK inhibitor and fulvestrant with our selective CBP degrader reveals a deeper effect shown in the green box. This data reveals an important dependency for CBP in ER-positive breast cancer beyond the synthetic-lethal relationships that we have previously characterized. Representing the flip 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 where there is a lineage dependency on EP300 with no CBP mutation. As we demonstrate here, a broad range of hematological malignancies are dependent on selective EP300 degradation. 70% of the cell lines tested are sensitive.
Focusing on the multiple myeloma results at the far left of the graph, we see that all of the cell lines that we have profiled respond to our selective EP300 degrader. The in vitro results that I just showed you translate nicely into the in vivo setting shown here. I'm extremely excited by the complete regression shown by our selective EP300 degrader shown in the middle panel in blue. We also include a dual CBP EP300 bromodomain inhibitor, and that molecule achieves tumor stasis shown in gray. We are excited by the superior efficacy demonstrated by our selective degradation approach. Complementing this efficacy shown in the right-hand portion of the slide, we measured platelets at end-of-study and are gratified to see that our approach spares platelets, whereas the dual inhibitor has a significant effect on platelets. Additional data from our selective EP300 program will be presented tomorrow.
Turning to our ARID1B program, we are at an earlier stage compared to CBP and EP300, but we are making strong progress. A key reason to highlight ARID1B is the frequency of mutations in ARID 1A, which is ARID1B's paralog seen across several cancers. ARID1A mutations render tumors dependent on ARID1B, and blocking or degrading ARID1B could therefore be an important strategy for effectively killing cancer cells. ARID1B is an extremely important target to us, as it is one of the most highly mutated targets in oncology and represents a significant unmet medical need. Looking more closely at the ARID1A mutant population that we would hope to address with a selective ARID1B degrader, we see significant unmet need across a range of tumor types, including uterine, bladder, and stomach cancers, among others. ARID1B is one of the most challenging targets that I have worked on in my career.
This is because ARID1A and ARID1B are very similar to each other, making selectivity challenging, and also due to the fact that ARID1B is not an enzyme and is roughly half-disordered. Our approach has been to first obtain selective binders to ARID1B and then to convert these binders into selective degraders. I'm especially proud of the fact that we have obtained selective degradation of ARID1B, and we look forward to providing a more detailed update on this program later this year. I will now turn the call back over to Adrian.
Thank you, Steve. Continued progress with FHD909 and our pipeline programs represent important drivers of value inflection for Foghorn. With the data we are showing at AACR and updates on our clinical plans, I hope you have a better understanding of the enthusiasm we have for the advances we anticipate throughout this year.
Based on our track record of engineering promising selective therapeutics that target gene regulation, we are positioned to be a durable leader in this area of novel biology. We are well capitalized and, as of December 2024, had $243 million in cash with cash runway into 2027. The stage is set for Foghorn to deliver significant value with differentiated, high-impact medicines in 2025 and beyond. Thank you, everyone, for attending today's call. Tara, you may now open the line for questions.
Great. 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 sharing this new data and congrats on all the progress. I just wanted to ask two questions on the ongoing phase one trial. First, for the backfill cohorts, I mean, you alluded to enriching them for NSCLC patients. Are you able to enrich them for any other characteristics, such as class one loss of function mutations specifically?
Yes, we do have the ability, as we dose escalate, to select specific doses, specific dose levels, and backfill those levels with specific indications as well as specific SMARCA4 alterations.
Great. I'm aware that you'll have to align on your partner, Lilly, with this, but at this point in time, how do you anticipate communicating trial progress? Should we expect to hear when you advance the dose escalation or dose expansion, excuse me, will you provide any updates on progress with the escalation and the backfill cohorts along the way? Just kind of big picture, what should we expect to hear over the rest of this year?
Yeah, thanks, Gavin. This is Adrian. Our intention, obviously, is to be very aligned with our colleagues at Lilly on when and how we disclose clinical data. Our intent certainly isn't to do anything piecemeal or in dribs and drabs, so I would anticipate that at the end of dose escalation, that would be an appropriate time to communicate clinical results. If there are decisions to proceed into expansion earlier or into combinations, we would certainly aim to communicate that. That is how we think about the overall communication plan. At this point in time, we don't have any specific time points at which we would communicate anything this year.
Got it. That all makes sense. Congrats on the progress. Thanks.
Thanks, Gavin.
Great. Thanks for the questions, Gavin. Our next question comes from Yaron Werber at Cowen. Please go ahead, Yaron.
Great. Thanks so much, and thanks for doing this. Quick, I have a couple of questions. Maybe I'll take them in order. The first one, when I'm referring to the phase one study with 909, are you thinking that you're starting at the active dose levels, or do you expect that you'll need to kind of progress to a few dose levels to have single-agent activity? Secondly, is there any way would you want to wait and lock down your dose before you start a combination with Lilly's KRAS inhibitors, or is there any chance to start them in parallel before you expand in this phase one B? Thank you.
Yeah, as far as the therapeutic dose range, this is no different from many other phase one trials. We anticipate that the first dose level will not be significantly clinically efficacious, and that will be achieved as we dose escalate. In that sense, this study is no different from any other phase one study. As far as combinations, we do have the ability to launch combinations before we end the dose escalation process. I think most likely we'll have to get very close to the end of dose escalation realistically to start launching combinations. In terms of combination partners, we haven't made a decision as of yet as to which ones will be the combinations that will move forward.
All right. Hopefully, Yaron, we didn't lose you on that. I think we're probably ready for the next question then.
Okay, great. Our next question comes from Kelly Shi at Jefferies. Please go ahead, Kelly. Kelly, you might be on mute.
Thank you for the presentation. I'm curious for how frequent for SMARCA4 and KRAS mutation co-occur and also in which indications?
Great. Alfonso, you want to take that?
Yeah, of course. Most of the data have been described in lung cancer. In lung cancers, SMARCA4 alterations rarely co-occur with other targetable oncogenic drivers, with the exception of KRAS. Approximately a quarter of the KRAS mutated patients will have SMARCA4 alterations. It is a sizable patient population and one that is very attractive from the point of view of combination studies.
Thank you. Thanks for the question, Kelly. Our next question comes from Paul Choi at Goldman Sachs. Please go ahead, Paul.
Hi, good morning, everyone, and congratulations on all the progress. The reception to Dr. Brooks' presentation seemed pretty positive in the room. My first question is just on patient identification, and could you maybe just comment on sort of are SMARCA4, SMARCA2 patients able to be identified through current standard panels, or is it mostly through next-gen sequencing? That is my first question. My second question is just maybe helping us to better understand the therapeutic index for 909. On slide 14, you reference a 60 mg per kg dose for that combination, but some dosing holidays. On subsequent slides, you reference a 40 mg dose for those combinations. Can you maybe just help us understand how you're thinking about the therapeutic index there? Does this data here, maybe at least for the combination, sort of translate allometrically into the human model?
Maybe just some color or bookends on that would be helpful. Thank you.
Yeah, so I'll take the patient selection question, then I'll let Steve comment on the therapeutic index. As far as patient selection, yes, the SMARCA4 alterations are very easily detectable with conventional FDA-approved panels, NGS panels. We also have the ability to select patients to the study based on immunohistochemistry on SMARCA4. So if tumors show loss of protein, loss of SMARCA4 protein expression, even within the absence of NGS data, those patients will be eligible for the study. Steve?
Yeah, with respect to the doses that we used in the in vivo models, we did use dosing holidays at the 60 mg dose. That was not because of a lack of tolerability, and thus that does not, I believe, comment on the therapeutic window. The reason we gave those dosing holidays at the 60 mg dose is because in rodents, we see some accumulation at the top dose, and so we gave the holidays to correct for that accumulation.
Okay, that's helpful. Thank you very much. I'll jump back in queue.
Thanks, Paul.
Yes, thanks for the questions, Paul. Our next question comes from Kalpit Patel at B Riley. Please go ahead, Kalpit.
Yeah, hey, good morning, and thanks for taking the questions. Maybe a couple of preclinical ones here for the SMARCA2 program. I guess when you combined with the KRAS inhibitors preclinically, was there any signs of additive or synergistic toxicity profile, and what was seen, or was it largely overlapping?
Steve, you're probably best equipped to take that, and Alfonso can comment if necessary.
Yeah, as we pointed out, we saw synergy with the activity adding 909 with the KRAS approaches, but the doses were still tolerated.
Okay, got it. For the ongoing phase one program, given the learnings from what we've seen with Prelude so far, I guess how tightly are you enriching for SMARCA4 for loss of function patients versus the broader patient population?
Yep, during dose escalation, we are histology agnostic as well as SMARCA4 alteration agnostic. As I commented before, we have the ability and we will expand and backfill cohorts with specific indications as well as refine those cohorts for loss of function mutations. That will be taking place as part of the backfilling exercise.
Okay, got it. Thanks for taking the questions.
Thanks, Kalpit.
Our next question comes from Morgan Gryga at Morgan Stanley. Please go ahead, Morgan.
Hi, everyone. Thanks for taking our question. This is Morgan on from Vikram at Morgan Stanley. We have two questions on the earlier stage pipeline. First, looking at the ARID1B degrader program and the update that we're expecting later this year, what could we learn from this update? The second question, are you currently assessing any partnership interest for the CBP EP300 and ARID1B programs? If not, how far would you anticipate independently developing these programs before doing so? Thank you.
Thanks, Morgan. Steve, do you want to take the first question on ARID1B update?
Yeah, for ARID, as I mentioned, super excited that we've achieved degradation, selective degradation of ARID1B. We want to have a full story and not have a piecemeal story as we proceed. We're waiting a little bit longer to have a complete and robust story to disclose to you all.
Morgan, this is Adrian. With respect to your question on business development and progression of the proprietary pipeline, maybe just to start at the 50,000-foot level, the view from Foghorn is that strategic partnerships remain critical to building our company. Certainly, we've had the Lilly collaboration already. We're not in any rush to partner any asset, but with that said, we believe strategic partners ultimately can be helpful as we progress the rest of the proprietary pipeline. We don't have a specific must-have in terms of partnering any of those three assets, but I would anticipate over the coming 6-24 months that additional strategic partnership can be helpful to us with one or more of those assets.
At present, our goal always remains to try and maximize value for our shareholders, and we believe that progressing these programs forward, whether that's into the clinic or furthering them into the preclinical, as the case is for ARID1B, is still in the best interest of our shareholder value creation plan. That is sort of the high-level way that we think about it. I would anticipate, again, just to reiterate that we'll see more partnerships coming out of Foghorn in the coming years.
Great. Appreciate the color there and congrats on the progress.
Yeah, thank you, Morgan.
Great. Our next question comes from Robert Driscoll at Wedbush. Please go ahead, Robert.
Great, thanks. Morning, guys, and appreciate you doing this. Some really exciting data. Just a follow-on from Paul's question. How well have the SMARCA4 mutations been characterized in terms of kind of protein loss and kind of lack of activity and so on?
Alfonso, do you want to start with that? Maybe Steve can follow up.
Yeah, so in lung cancer, for instance, and I keep going back to lung cancer because it's the best characterized cancer when it comes to SMARCA4 alterations. In general, if you look at the literature, the incidence of these mutations ranges from 7-10%. In general, again, about half of them will be loss of function mutations. These are truncating mutations, stop-coding mutations, and those translate to loss of function, loss of protein expression. There is a very tight but not perfect correlation between those specific mutations and loss of protein expression. The correlation is a lot looser with other types of mutations. Does that help answering your question?
Yes, perfect. Thank you.
Great. Thanks for the question, Robert. Our final question comes from Silvan Tuerkcan at Citizens JMP. Please go ahead, Silvan.
Good morning, and thanks for taking my question. Congrats on the comprehensive update here. Just a question. Given this is a phase I, it's for very late-stage patients, but do you anticipate that we could get maybe some second-line or early-stage patients enrolled in the trial by the time we get to dose expansion? A second question regarding all the data you have with combinations here. Obviously, later this year, we'll get significant updates with some of the bispecifics, especially focused on small cell lung cancer. Any plans on studying your synergies here? I have a follow-up.
Alfonso. Yeah, thanks. Alfonso, do you want to take that?
Yeah, so in terms of the early-phase patients, the patient population in the study will be no different than other phase one patient populations. By eligibility criteria, these patients will have to have failed standard therapies. Depending on the indication, that will mean that we'll catch those patients in the second, third, fourth line. It will vary depending on the indication we're talking about. Typically, this is going to be a very standard patient population for this stage of development. As for the second question.
Yeah, it was some of the upcoming bispecific data, not small cell lung. How does that inform our thinking, if at all, on any combination measurements?
As these agents become mainstream and get incorporated into the treatment paradigm for lung cancer, those will become obviously combination partners. We're not very much focused on agents that have been approved, have a track record in lung cancer. We talked about combinations with chemotherapy, KRAS inhibitors, pembrolizumab, and other checkpoint inhibitors. Because those are the obvious combination partners at this point, that does not mean that in the future that will change. These agents, we're focusing specifically on these agents because those will be our gateway into the frontline setting in lung cancer. There is a lot of stress put on those agents because of that reason.
Great, thanks. Maybe one last question on your CBP degrader. You have a very great with your long-acting formulation here. Can you just talk a little bit about the PRISM screen that you presented at AACR and what that suggests in terms of indications for the CBP degrader beyond the EP300 mutant cancers?
Yeah, yeah, we're quite excited about the potential to expand the reach of our selective EP300 degrader beyond the EP300 mutant population. The one particular indication that we've spent most of the time or most effort characterizing is the positive breast context. We presented in vitro combination data there that I find quite exciting. There's some single-agent activity as well as deep combination activity to expand the reach of our CBP selective degraders. I guess the rest of your question is that beyond positive breast cancer, those screens did indicate that there could be combination potential even beyond the positive breast. We're looking into all of these possibilities.
Great, thank you so much.
Great, thanks, Silvan.
Yes, thank you, Silvan. This concludes today's Q&A session. I will now turn it back to Adrian for quick closing remarks.
Great, thank you, Tara. Thanks to everyone again for dialing in and listening to our update today. Thank you to our covering analysts as well for your questions. We look forward to keeping you updated as we make progress on both FHD909 as well as our broader pipeline. We look forward to talking with you guys again very soon. Thank you, everyone. Have a great day.