Welcome, everyone, to the next session with Olema Oncology. Reminder, I'm Yigal Nochomovitz, Biotech Analyst at Citi. If you have questions, feel free to raise your hands, and we'll take your questions here in the room. Also, welcome to those listening online. It's my great pleasure to have Olema Oncology CEO, Sean Bohen. Welcome, Sean. Thank you, Yigal. Thank you for coming. A lot to discuss, obviously, and you had some news this morning as well, which we can get to in a minute. Maybe just to set the stage, if you could just give everyone the high-level overview of the pipeline, what you're focused on. Obviously, breast cancer, but just kind of review some of the studies and we'll get into the details from there. Right. Great. Thank you. And thanks for the opportunity to talk about Olema. Olema is a targeted oncology company focused on treatment of ER-positive, HER2-negative breast cancer. Our lead asset is a molecule called palazestrant, which is a complete estrogen receptor antagonist. That molecule is in phase III, two phase III trials, in fact. The first is a trial called OPERA-01, which is in the second, third-line setting for advanced metastatic breast cancer. These are patients who've progressed after their initial therapy of a CDK4/6 plus aromatase inhibitor, and that's as a monotherapy that it's being tested. That trial is enrolling nicely and will read out in the second half of next year. Two great opportunities for differentiation there. One is better activity in the ESR1 mutant population, where we in phase II showed over seven months of median progression-free survival, and also to show activity in the ESR1 wild type population, which has not yet been demonstrated by other molecules, other endocrine agents. We showed five and a half months of progression-free survival in the phase II setting. The market opportunity is $2 billion- $5 billion, we believe. The range has to do with whether you get mutant-only or mutant and wild type. The other phase III trial, which will initiate this quarter, is in the first-line setting. We believe a $15 billion+ market opportunity where we will be testing ribociclib plus palazestrant versus ribo plus AI, the current standard of care. That's called OPERA-02. That trial will begin enrollment soon. We will also present updated data with that combination in October, in about six weeks, at ESMO, in particular, ribo plus palazestrant in the post-CDK4/6 setting, where we've shown over a year median progression-free survival, which is unprecedented. We're also going to break out the wild type and mutant so people can understand that there is an opportunity for activity in the wild type setting. We have another molecule, which is in the clinic. It's a KAT6 inhibitor called OP-3136. That's progressing as a monotherapy in phase I, and we just started dosing patients with the fulvestrant combination. Soon, we will begin also combining with palazestrant, which showed remarkable activity in preclinical models. We anticipate, in the first half of next year, presenting combination data of OP-3136 with fulvestrant and palazestrant in addition to the monotherapy. We're combining with a variety of agents. The announcement today for palazestrant was a clinical trial supply agreement collaboration with Pfizer to combine with their CDK4 selective molecule, which they have in pivotal trials in the first-line setting, atirmociclib. Okay. Yep. We saw that. I guess tell us a little bit more about that one, because, of course, you already have the ribo combo. TRMO is another interesting molecule, but what advantages does having that combo give you? Just an optionality in terms of multiple options for future use? Yeah. I think there are a number of things, right? I think if we go back to looking at the treatment paradigm in ER-positive, HER2-negative breast cancer, the objective is to stave off chemotherapy as long as possible. The way that you do that is to treat with targeted agents. The first line for that, for now, is pretty well established. It's ribociclib plus an AI. We know AI's have a common resistance mechanism with CDK4/6s, and that is ESR1 activating mutations, which can be suppressed by palazestrant. We also believe palazestrant is better in the wild type setting, so there's the opportunity to extend that first-line therapy with ribo. All of the targeted agents require an endocrine therapy, and we believe palazestrant is the most effective endocrine therapy or has that potential. In the case of this is the lead pipeline molecule for Pfizer, which has a great commitment to and a large franchise in breast cancer. The hypothesis there is that more complete inhibition of CDK4, which can be achieved by dialing out the CDK6, which causes neutropenia, may lead to greater efficacy. They're testing that in an ongoing first-line phase III trial of plus AI versus CDK4/6 of physicians' choice plus AI. There is the belief that endocrine therapy will advance as well, and they're combining with palazestrant in order to understand if that may be an enhanced future therapy. For us, it is another opportunity to extend the lifecycle of palazestrant. Could this lead to more with Pfizer? I mean, it's a small study. It's a supply agreement. It's only 35 patients. Yeah. Does it open the door to something more with them if the data look good? Potentially. I mean, that's what we did with ribociclib, obviously. We did it with palbo as well. We had a prior supply agreement with Pfizer that was for palbociclib. The reason that didn't continue, the combinability was excellent. Palazestrant combines with palbo, ribo, alpelisib, everolimus ongoing. Now, we'll be The reason we didn't continue with the palbo combination was because the overall survival data switched the standard of care to Kisqali ribociclib, and we went in that direction in our phase trial. I think if we do show favorable combinability and efficacy, the opportunity to expand into a pivotal trial exists, or certainly to generate more data. We have to do this step first, and that's what the agreement allows us to do. Which line is it, and is it wild type and mutants or a mixture? Yeah. I mean, again, it starts out as a phase 1B component, so that you're dosing with and 60 mg of palazestrant and then 90 mg, which is the phase III dose. After a short safety run-in, you can then expand. In those original lines, you sort of take the patients you can get, so we think they'll mostly be post-CDK4/6. What we saw with the ribociclib combo was once our investigators, and it's the same investigators, actually became comfortable with the combination, they started moving first-line patients on to the trial. We anticipate it'll be a mixture of patients as we expand it, some post-CDK4/6, some treatment naive in the advanced or metastatic setting. Has this particular combo of palazestrant and atirmociclib been seen in humans before? This will be the very first. This is the first time in humans. This will be the first time. What they have tested with atirmo for combination so far is obviously AI, and also they did some fulvestrant testing. The phase III that they are doing right now is really comparing CDK4/6 versus atirmociclib, and the endocrine backbone there is the existing one for first-line, which is aromatase inhibitor. Right. Okay. You mentioned ESMO, where you're going to have the follow-up data for the combo. Yeah. You showed, I think it was in February, if I'm not mistaken, of this year, the initial PFS, which was somewhere in the neighborhood of 13 or so. Yeah, it's a bit more than a year. Yeah. Tell us a little bit more detail. What additional, you mentioned wild type versus mutant, so it'll be longer follow-up, more rigor on the PFS conclusion. Yeah. What else would we be getting at ESMO? Of course, it's more visibility because when you showed us the data in February, it wasn't at a medical meeting, right? It was just in the context of. Yeah, an investor. Right. That's right. This is going to be in the context, obviously, of a publication at a medical meeting presented by our lead investigator. First of all, it's the same dataset, but more mature, as you said. That dataset had first-line patients and second-line post-CDK4/6, some actually post-CDK2 fit, prior CDK4/6 inhibitors, which is interesting. We still see activity with all that prior treatment. This will be more follow-up. In addition to the additional follow-up, which will create a more accurate point estimate of the PFS, most of those patients were actually wild type. We're going to break out the wild type and the mutant subsets because there is question in people's minds, can a next-generation agent have activity in the wild type setting post-CDK4/6? Because so far, it's been pretty disappointing. We think our phase II data is quite encouraging, but we're going to help people see the potential we view in the mutant, which I think is generally accepted, but also in the wild type setting post-CDK4/6. The first-line patients, it takes a long time for that data to mature because, obviously, they are able to maintain treatment for a long time. The median PFS in the pivotal trials for Ibrance and Kisqali and Verzenio was 24 to 25 months. That takes a lot more follow-up to ensure. Right. Is another benefit of showing this data at ESMO to kind of advertise the phase III trial? Absolutely. Believe it or not, when you go to a meeting like ESMO, I hate to say this, but the primary audience is not investors or analysts. I know it's shocking. Yeah. It really is potential investigators and experts in the field. As well, to some extent, it's the patient advocacy organizations, right, who are helping patients identify treatment options as they make their very important treatment decisions. It is a great opportunity to, we've had great interest already because that trial is being initiated right now. I think to generate general interest in enrolling patients in the trial and in patients being on the trial, the way to look at it is these are post-CDK4/6 patients. They will have had one, sometimes two prior CDK4/6 inhibitors. They will have radiographically progressed. Now, we're giving it ribociclib plus palazestrant. What you can think of is if you were to start this therapy at the beginning, you would be getting the benefit of it all the way through. You can think of it roughly as an extension on the benefit they already got. I think that that will be encouraging to investigators and patients, and investors and analysts would be great too, or happy to talk about it. Is the study in the ramp-up phase, or have you actually enrolled the first patient? We haven't dosed it yet. Not yet. No, we haven't. All of the regulatory interactions are completed. This is a 1,000-patient global study, so there's a lot of logistics involved. We're getting all of that IRB approval and sites activated. We will initiate that trial during this quarter, during the third quarter. That's by the end of this month. Yeah. Okay. You're comparing versus letrozole and ribociclib. No. The comparison, yes. It's letrozole. Exactly. I'm sorry. It's ribo- letrozole versus ribo- palazestrant. Right. The endocrine therapy comparison is letrozole, but the regimen is the existing standard of care, which is ribo-AI versus ribo-palazestrant. I guess what I was getting at is, you know, how should everyone be thinking about the threshold on the primary endpoint. Yeah. Which would be compared to letrozole versus ribo, although, of course, the standard of care therapy was also a relevant comparison, potentially. Right. If we think about what we're seeing, has been seen in multiple trials with ribo plus AI, it was about 25 months of median PFS. That's the PFS as the primary endpoint. We believe, in interactions with investigators, oncologists, regulators, that what you would need to drive approval, to drive reimbursement use, is about a six-month improvement in that median. Go from about two years to about 30 months. Okay. I think that that's a useful number to have in mind when you look at the data we're going to share at ESMO. Right? Think about these patients have already progressed on CDK4/6, about 30% of them on two prior, and then what are we able to extend beyond in that population? We think it's encouraging. For people that are less familiar, can you comment on that there was a decision to do 90 mg in the phase III? Yeah. Versus, I believe, a slightly higher dose previously. Yes. Can you remind everyone what the decision point there was to go to 90 mg for the phase III? Right. This is a Project Optimus request. Okay. That you can't refuse, kind of, from the FDA. We had previously done 60 mg and 120 mg, had chosen 120 mg. They agreed with letting go of 60 mg, but they wanted 90 mg and 120 mg. I think the main motivator there was the exposure is essentially the same. We've shared that. Okay. It's on our website. You'll see some of that data in the poster as well. It was a safety and efficacy-based decision. I should say that the recommendation came from our independent data monitoring committee, which was unblinded, and then made a recommendation with that data available to the FDA. In that respect, it's not the company that makes the recommendation. We actually were fine with going with 90 mg throughout because there is no exposure difference between the two. Both are completely overlapping, as you'll see in the data and will have seen. Also, with the completely overlapping exposure, both of them far exceed our preclinically defined exposure targets, so we're quite comfortable. Okay. I think you've talked about the duration. Do you have sort of sub-analysis in the genetic segments, the wild type versus the mutant, in terms of a pre-specified PFS on each, or is it going to be you're looking at the whole thing, or is there a staggered hierarchical, like as others have done? How are you approaching that? Right. I'm going to separate it into two questions. I'm going to separate it into an OPERA-01 question, the second, third-line setting. Yeah, sure. Okay. The OPERA-02, right? In the OPERA-01, this is very important. Right. Right? Because what we've seen is a few agents get a modest but real benefit, about two months increase in PFS, only in that mutant setting. The way OPERA-01 is designed is the patients are stratified by mutational status coming in. Remember, these patients have already progressed on a CDK4/6 plus an AI. 40%- 50% of them we expect to have their tumors have an ESR1 activating mutation. The trial is designed to test the activity of palazestrant versus standard of care fulvestrant or exemestane in the ESR1 mutant and separately the ESR1 wild type populations. That is the regulatory standard now, and that's the opportunity for differentiation. We haven't gotten into the details of exactly how that statistical design goes, but the trial is powered and designed to test them independently. You do have the outcome, the PFS is higher in mutants, so you do have the outcome of mutant only. The question is, can you do better than two months? We think we can based on phase II, but you have to do it in phase III. Can you have adequate activity, at least two months increase in PFS in the wild type population? It'd be clearly differentiating. That's the OPERA-01 question. OPERA-02, it's not really, it's a bit of an exploratory endpoint. The percentage of mutation in patients who have not been treated for advanced or metastatic disease is going to be in the low mid-single digits. Okay. You can't really power anything. You don't stratify based on it. You can collect them and see how they do, but really, the power in that mutant population is preventing the occurrence of the mutation as a mechanism to progress on the therapy. Once the mutation arises in the ribo letrozole arm, we know the patients will progress quickly. We think it will be suppressed. Yeah. In the ribo palazestrant arm, which in addition to the activity in the wild type is an opportunity to expand that progression-free survival. For 02, you're starting, as you pointed out, this quarter. Given what you said about median PFS for control and active, sort of like the average of that is in the high 20s. The readout of this study is going to be, you haven't set a specific time yet, right? Yeah. You can do the math a little bit. Yeah, I mean, if you take a year to enroll and you take two plus a bit, you're a few years out from here. Yeah, yeah. Okay. Yeah. But that's. OPERA-01 will read out second half of next year. Yeah, that's the second line. Yeah. For the OPERA-02, that's to be expected. That's just first-line breast cancer. It'll take a few years to read out. Yeah, we have active treatments there, right? Yeah. I mean, that's the good news. Yeah. The challenge is that another way of looking at it, Yigal, is that the timeline for OPERA-01 is driven by enrollment, right? Because the median in the control arm is going to be two to three months. Right. Once you've enrolled, events accumulate fairly quickly. Sure. This is not the case in OPERA-02. Enrollment's vitally important. You got to get the patients on the trial and start the clock. The timeline is driven by the accumulation of events, which is much more protracted. The other important thing about OPERA-02, which we didn't get to yet, we mentioned ribo. We didn't talk about, when was it? It was last year, the supply agreement. When did you announce it? November. Last November, right? Yes. Talk a bit more about that. I don't think that got enough air time because people didn't understand the full significance of that, you know, operationally and also financially. Yeah. If we talk about OPERA-02 as a trial, it's about 1,000 patients, right? These are patients who have not had advanced treatment for their advanced or metastatic disease. That treatment has shifted because of the survival benefit, right? The only NCCN category 1 treatment in that setting is ribociclib plus an AI, and that's based on a survival benefit, which was not demonstrated with Ibrance or Verzenio, only Kisqali. That was what we wanted to test. Uniquely, we're the only ones partnered in the first line with ribociclib. If you look at the trial, the overall trial cost is something around $500 million. Interestingly, if we do it ourselves, about half of that, maybe a little more, is actually the cost of Kisqali because every patient on the trial is going to get it. As we talked about, it's about 25 months median of it on the control arm. We hope significantly better on the treatment arm. The way we are able to do this trial is two things. One, we did a PIPE and raised $250 million at that time. The second is that we have a collaboration with Novartis, where they provide the Kisqali for the trial. It isn't them giving us, you know, up to $300 million, but it offsets for us the potential cost of up to $300 million of Kisqali. In exchange for that, they get some rights. They get a right of first offer for a collaboration. Collaboration effort would probably be triggered by the readout of OPERA-01 second half of next year. For M&A, if we decide we don't like their offer, we can refuse it and then go to whoever we like. We cannot do collaboration with more favorable terms to another party than their last offer. With regard to M&A, it's a much more restrictive interaction. They have a notice right. If we get an offer to acquire, we notify them that we have a viable offer, and we talk about the structure. You know, is it cash? Is it cash plus equity? We don't talk about the actual numbers, the financials of it. Those were the rights that we exchanged for that. Okay, they get to decide what to do with that information. Yeah. Yeah. Right. Yeah, if they want to act on it, they can act on it. Yeah. They can choose not to. If someone else acquires us, they get some reimbursement rights for the drug. In that case, what you've done is you've gotten kind of an interest-free loan for the cost of the Kisqali. Right. Okay. Gotcha. Okay. You mentioned some of the data from the prior phase I, II for the monotherapy, the 7.3 and the 5.5. Right. Now, that was with 120, but you pointed out that the exposure is essentially the same at 90 mg. Exactly. Would you expect similar behavior in the OPERA-01 on that? We would, and the IDMC got to look at efficacy. I mean, I don't know how they made their decision, I'm not 100% sure. I do know they had it. Okay, that's coming the second half of next year? Correct. Remind us, has that finished the enrollment or you're still. No, no. Right there. Hasn't. Remember, maturation of that trial from an event standpoint is going to be relatively quick just because. Like I said, yeah. The standard of care, the control arm, has been pretty consistently two to three months across other trials, and that's what we expect. We will be able later this year to refine from a half to a, you know, at least probably a quarter as to when the readout will be as we get more enrollment data. It is enrolling now, and it's enrolling well. Okay. Before we talk about the KAT6, and you mentioned some combo studies, which are interesting, can you just talk a little bit on the basic science? We've skipped over it. The palazestrant, you've talked about it in terms of the mechanism as a SERON/SERD. Right. What's the latest statement there, and how does it compare to quite a few of these oral SERDs out there? What's the differentiation aspect on the mechanism relative to? Right. Palazestrant, giredestrant, and imlunestrant. There's a few of them. Yeah. Yeah. It's different for different ones. We think the primary molecular characteristic that is necessary for palazestrant is being a CERAN, a complete estrogen receptor antagonist. What this means is when it binds the estrogen receptor, wild type or mutant, it just turns off all transcriptional activity. Essentially, it turns off the growth and proliferation signal that the tumor has hijacked in order to grow inappropriately. Some of the molecules don't do that. They're SERMs, so they partially turn off in the mutant setting, but they turn on in some context in the wild type setting, which makes some sense as to why they wouldn't work in the wild type. Vepdegestrant, our venous molecule, palazestrant from Olema, they act in that way. There are, as you point out, other CERANs, complete antagonists. Giredestrant from Roche is one. Camizestrant from AZ, for instance, the two that are in phase III trials with palbociclib. The challenge then becomes about pharmacology. We get considerably higher exposure with once daily oral dosing. That's what they also use for exposures higher. Combinability also has to do with tolerability. Roche had to reduce their dose from 100 mg to 30 mg because of bradycardia with palbociclib. Camizestrant can't go above 75 mg. It's a much lower exposure because of ocular and cardiac toxicity combined with palbociclib. We have been able to achieve a pre-specified exposure target both at 90 mg and 120 mg in combination with full dose ribociclib, full dose palbociclib, all of these agents, and obviously ribociclib is most relevant because that's what's moving forward. It's a combination of underlying molecular property being a CERAN as well as exposure and combinability and tolerability. Okay. What sort of, for these two phase III trials, I guess starting with 01, are you going to give some incremental updates before the data, like just narrow the timing down or get enrollments done? As I mentioned, I think we can definitely, you know, hopefully before the end of the year, narrow the timing a little bit for the data, just when we have more enrollment data. Right. OPERA-02's got a ways to go. I think at some point we will most definitely guide people as to when we expect a readout, but we're a ways off from there. Of course. We're more guiding around initiations. I want to go back, Yigal, to your question about how we differentiate. I think the most important part of differentiating is how it's translated into the data we've generated in phase II. There is a propensity of investors to equate all these molecules under the SERD. Unfortunately, degradation is not the mechanism of action here. It's a bit of a misbranding. Our phase II data looks exceptional, both as a monotherapy and in combination with ribociclib. Phase II data's been pretty accurately predictive of phase III outcome in this space. We're hopeful that that is the case for us as well, because if it is, we should maintain that differentiation. Did you ever get into the weeds on the power? I mean, you've talked about the numbers, the median PFS, the GILBERT PFS. Did you ever talk about the powering and hazard ratios? You never got into that level of detail with the investors. We haven't. What it's powered for, and so forth. We have talked about the thresholds we believe we need to achieve. Yeah. In the first-line setting, the threshold is a two-month increase in median PFS. That's one radiographic evaluation, right? That's two cycles, but one radiographic evaluation period is eight weeks. That is what was achieved by elacestrant in the mutant population and led to approval. There's no effect in wild type, so obviously no approval. That's what Veritac-2 also achieved, and we think will lead. You mentioned you expect to be better than that. We do expect to be better than that. Right. In the mutant in particular. If the wild type, we think if we can achieve it, it's the same. It just hasn't been, it's the same threshold that's needed, it just hasn't been achieved yet. A little different in the first-line setting, that wouldn't be adequate. We think it's six months. You know, recall ribociclib has a survival benefit. Now, both arms are getting ribociclib, so that acts to our advantage. Patients and physicians don't have to decide, "I'm going to give up this drug that has a demonstrated survival benefit." It's just changing the endocrine therapy. We think six months is going to be what's required to get regulatory approval, reimbursement, change physician and patient behavior. Anything to comment on the tolerability side? Of course, that's also important, especially when you're combining drugs. You mentioned, of course, with the combining with atirmo, you won't have to deal with the CDK6 aspect. Yeah. Neutropenia. Anything of note on the palbo side of things? Yeah. I don't think so. I mean, we are generally very well tolerated. There were concerns earlier on. We have a single-digit, kind of mid-single-digit neutropenia, reversible neutropenia. Many of the patients restart and continue on the drug after recovering. We don't know the mechanism. I think the concern was, you're going to combine with palbo, which has neutropenia as its dose-limiting toxicity. You're going to combine with ribo, which has less, but it's still the most frequent reason for dose reduction. What's going to happen? That's already established. Nothing happens. If you look at, and we'll update again at ESMO, if you look at our ribo, palazestrant combo, the profile looks very much like ribo AI. We feel like you can substitute this once-daily pill, and physicians really can do their same monitoring that they would for the established care and expect similar tolerability. By the way, that data's mostly generated at 120. I don't know, again, what the IDMC saw exactly, but I don't think 90 mg will be worse. I would agree. Yeah. Yeah. Okay. I wasn't sure if this was sort of new statements. The combo with, speaking of the KAT6 now, the combo with fulvestrant, the combo with palazestrant. I know I probably asked about the idea of doing those together, but tell me more about those combo studies because I thought we were doing a mono TX phase I with the KAT6 to start. Yeah. You're doing both. All those are true. Yeah. Yeah. It is a fairly new update. It was always our intention to combine. Look, all of these targeted therapies are not given as monotherapies. They're given in combination with endocrine therapy. In the post-AI, that's usually fulvestrant. That's why with a slight preference because it's a big injection and we don't think it's the best endocrine agent, but we need it to compare, right? Yeah. You have to start a new molecule with monotherapy. I think, and we're still dose escalating in monotherapy, but based on what we've seen, we were able to accelerate the start of the combination. Patients actually are being treated with fulvestrant plus OP-3136 now. That's started. Yes. Okay. We'll do kind of in parallel. That's really new. Yeah. Before the end of the year, we will start palazestrant combination there too. By virtue of that, what we've decided is it's better to be able to share not only mono, but also some combo data. Going into next year allows us to do that. We'll be able, our first OP-3136 presentation will be more informative than just a monotherapy. Okay. There are a few of these in the space beyond your KAT6. Some other companies have some. What can you say in terms of how yours is distinct from? Yeah. The one we compare to mostly is really the Pfizer molecule, which is in phase III and has clearly demonstrated efficacy with fulvestrant. We'll have to see how it plays out, obviously, clinically. Their primary AEs, they did not have an MTD, but their primary AEs were dysgeusia, an alteration of taste. Yeah. Cytopenias. What we are thinking is that part of that may have to do with KAT6 selectivity. KAT5 in particular and KAT8, we have less potency toward. We don't think they contribute to the efficacy. We're hopeful, and we'll see in the clinic, that we may be able to get a better therapeutic index with those dialed out. There is another way to differentiate, even if really we're relatively similar, which is if you look at our preclinical data, fulvestrant definitely adds, as you would expect, to the efficacy, but palazestrant does so much more impactfully with both of them, both with the Pfizer molecule and with OP-3136. Because we're the only company with palazestrant, we're uniquely able to do that combination. We're very interested in getting that going. You're saying the KAT5 and KAT8 with the Pfizer molecule may be contributing. Yes. You have dialed that down. You have dialed that out. We have dialed that down. Okay. We'll see, obviously, how much exposure you have in the clinic versus that does determine the clinical tolerability profile. That's something that's ongoing. What about OP-3136? There's another one. There's the OP-3136. How did you think about that one? Yeah. We also hit KAT7. We hit KAT6A and KAT6B. There's a very clear rationale to that. We had a concern that KAT6B could compensate for KAT6A, so that if you hit 6A only, 6B would take over. There's actually, earlier this year, a Nature paper, KAT6A deletion in mice is embryonic lethal. You can rescue it completely by overexpressing KAT6B. We do think that they can replace each other. KAT7 is something that both we and Pfizer hit. We're not quite sure what its role is, but I will say I wouldn't say that we distinguish from Pfizer in that respect. Okay. In the last minute or two, I mean, you're very much focused, as you should be, on breast cancer. Are you looking at other areas like prostate or lung? We are. The dose escalation for OP-3136 has castration-resistant prostate and non-small cell lung as histologies that we can look at. We saw activity in preclinical xenograft models in those two tumors. We are opportunistic that way. Obviously, the expansions with fulvestrant and palazestrant will only be positive, HER2-negative breast. I think we're going to have to, as we expand the monotherapy, assess whether there is an opportunity to expand in other histologies. Okay. I think we're just about at time. Thank you so much, Sean. A lot to look forward to. We'll check out the ESMO data soon. Yeah. Yeah. Thank you, Yigal, and thanks everyone for taking the time and your interest.