Sean Bohen, CEO of the company. Sean, welcome. Thank you, Rich. Glad to be hosting you for another year at the GS conference. We have a lot to talk about. Thank you. There's a lot going on. A lot of stuff coming out later on this year as well. Before we go there, I'm going to turn it to you for opening remarks. Great. Thank you, Rich. Well, thanks everyone for your interest. Just reminding you, Olema is a company focused on changing the treatment paradigm for ER+, HER2- breast cancer. This is the most common malignancy in women. It's the second most common cause of cancer death, ER+, HER2-, 70% of it. We have two clinical phase assets. The first is palazestrant, which is in two phase III programs ongoing. Their first readout, as we will talk about, to be in the fall from OPERA-01, our monotherapy. We recently presented data on our KAT6 inhibitor at ASCO, showing monotherapy activity both in ER+, HER2- breast, but also castration-resistant prostate cancer. The combinations are ongoing for breast and to be started for prostate cancer with that molecule. Great. Can you remind us of the cash position you guys have, the runway guidance, and what does it include and not include? Yeah. At the end of Q1, we had about $505 million, just a little north of a $500 million on our balance sheet. That will take us nicely into the second half of 2028. That is with the execution of OPERA-01, continued execution of OPERA-02, our first-line trial with KISQALI in breast cancer. Certainly, the remainder of the phase I/II for OP-3136, and also our efforts to file, assuming OPERA-01 is positive on palazestrant, to start commercialization. I see. Okay, fantastic. Let's kick it off with the KAT6 because you guys presented that data at ASCO. Yes. What are the key highlights there? I should first set context. This is monotherapy dose escalation data with the molecule. This is an oral daily pill for inhibition of KAT6. The trial allowed three histologies. It allowed ER+, HER2- breast, where KAT6 is a validated target. It allowed castration-resistant prostate cancer and non-small cell lung cancer based on our preclinical data. With non-small cell lung cancer, we had only one patient, not really much data there, but we saw single-agent antitumor activity in ER+, HER2- breast cancer and in castration-resistant prostate cancer. In addition, PK supporting that once-daily dosing with about 12-hour half-life and very good exposures. Good pharmacodynamic markers even at the lowest dose, and clinical activity across a variety of doses. We also saw what we think is more favorable tolerability. There was Grade 1 and less so Grade 2 dysgeusia, the taste alteration that is a class effect. We saw less cytopenias than at a similar phase what Pfizer saw. In breast cancer, we saw 22% Grade 3 neutropenia, which is about half of what Pfizer saw. We are hopeful that that will carry through as we get into the combinations. The fulvestrant and the palazestrant combos are ongoing. We did not present any data. Yeah. We recently signed a supply agreement in collaboration with Bayer to combine with their androgen receptor inhibitor, NUBEQA. Right. When we look at the data, like you said, it's monotherapy only. There's no combo data yet. Yes. That's going to come potentially later on this year, or- The optimistic is we might be able to have some, particularly from fulvestrant. Fulvestrant's only one dose level behind monotherapy by the end of the year. Certainly, for start of next year, we would have both. I see. Okay. Given that we only see the monotherapy data- That's right I think for Pfizer, we've seen their monotherapy data. We see some combination data. Yes. It's hard to compare the monotherapy data set because it's hard to know what the follow-up period is. Yes. That's fair I mean, is that a fair statement? Yes. This is still too early to know how, from a safety perspective, but we have seen from the Pfizer's KAT6 program that they have the combination data. I think they have with fulvestrant with the two different dose levels. We have seen what that looks like from the Grade 3 neutropenia perspective. Yes. To compare, you have to really compare the combination, right? Because those are you know the follow-up period versus monotherapy. Is that a fair statement? Well, you could. The thing is that for the tolerability, follow-up period is less important because this neutropenia shows up very early in the treatment. Certainly, for the response, it is important that there isn't as much follow-up because this is primarily a cytostatic, not a cytotoxic mechanism, it does sometimes. We saw it in our data set, but certainly Pfizer saw that patients responded over time. More follow-up can be useful. I think that we have less neutropenia is probably pretty certain. We also don't see dose dependence in neutropenia. They did see dose dependence in neutropenia. I think by dialing out CDK5 and 8, we may have created a different tolerability profile. Right. I do think that for response rate, and certainly response in combination, which we haven't shown any combination data, that's the really relevant efficacy marker, it does require more follow-up. That's true. Right. Okay. Got it. Does it make sense to think about the KAT6? I know the combination is just the KAT6 plus pala or fulvestrant. Does it make sense to think about KAT6 plus pala plus CDK4/6 in that first-line setting? No. Am I jumping the gun? Yeah. No, you aren't. You are not jumping the gun. I think we do need more tolerability data. The reason I say you're not jumping the gun is it's actually written into the protocol. Yeah. We have that option already. Okay. Yeah. It's not to bring up something. Yeah Had anticipated. As everyone knows, CDK4/6 inhibitors, their primary AE is neutropenia. Yep. The question was, will we have a low enough neutropenia rate in the breast cancer patients that we thought we might be able to bring that in? I think we're still evaluating that, but the initial data suggests. It may be a possibility. Right. That, when we first looked at pala has higher neutropenia than other SERDs, but when you combine it, you don't see that additive effect. No, that's. That was an interesting observation. It's exactly right. We have a mid-single-digit rate. Yeah Of neutropenia. Most patients with a pause are able to continue on the therapy, sometimes at a lower dose. I think the big concern that primarily investors had was, well, when you combine with CDK4/6s, are you going to exacerbate this thing? Yeah. Remember, our first CDK4/6 we combined with is the one that causes the most, which is palazestrant, IBRANCE. There was no enhancement. Right. We've seen that with LYNPARZA as well. Exactly. That was interesting. I have an idea. I've been thinking about this even before ASCO. Ken, wait until I ask you this. Have you thought about the possibility of going to the first line with just KAT6 and pala and just skip CDK4/6 altogether? In case there is Wow. An overlapping toxicity between KAT6 and CDK4/6, why not just go KAT6 and pala? Do you have to have CDK4/6? Yeah. I'm thinking from a regulatory standpoint, I won't do that right now. Think about it from a efficacy standpoint. I think if the pala combo data. Which initially will be in post-CDK4/6. Yeah. Treated patients. Yeah Okay, obviously. If that really is compelling, then I think it does raise the question, could you use that combination in the first-line setting? Now, obviously, if you can then you have the opportunity for a triplet. Yeah. I think that's a pretty straightforward thing. Right. If the tolerability Sure. Is adequate. It has to be- If not. Yeah. If not, I think it depends upon the efficacy we see in that post-CDK4/6 setting, and then I do think we have to think about what will be the regulatory pathway because we won't have OPERA-02 data yet- If we were to do that. I'd have to think about the regulatory pathway. Right. It would be two novel agents. That's what I'm worried about. That's exactly. By the time you would kick that study off, Pala would have been approved. Potentially by OPERA-01 in the second third line setting. Exactly. Yep. Yes. You also showed KAT6 in that NSCLC and CRPC. What's the development plan now looking at this, like these two new- Yeah. Areas? You guys have been traditionally focused on breast cancer. Now- Yeah. Is there an expansion into these other areas? There is. We've always said that we will not develop an agent unless it has an indication of breast cancer, ER+, HER2- breast cancer, that certainly is the case with KAT6. We've also said that's not how cancer works. Cancer pathways, the signaling pathways that contribute to evolution of cancer are often used in multiple cancer types, that is the case here for KAT6. Preclinical data said castration-resistant prostate and non-small cell lung. We only got one lung cancer patient- Yeah. We really don't have very much data. We got 10 prostate cancer patients, most of whom were treated with prior chemo and/or prior radioimmunotherapy, we saw clear antitumor activity. Our next step there is to expand in phase I/II with NUBEQA- In the castration-resistant prostate setting, I think it is that signal that will tell us where to go. For lung cancer, we have to think about whether we want to try to expand there. There was also great preclinical data in ovarian cancer, the standard of care is very complicated. Now that we have a path forward in other histologies- It might be worthwhile. Okay. Got it. How's the OPERA-01, OPERA-02 trials going? Remind us when should we see data? Yeah. I know you said fall. Is there early fall, late fall? How should we think about it? Also for OPERA-01, what data will you present? Is there any of this data that you think is mature enough to present? Yeah. The OPERA-01 is going very well. Yeah. It's certainly on target, and we are reiterating the top-line data in the fall. I anticipate that that will be a top-line press release. Okay. Sort of it hit, it didn't. Beyond that, it depends upon Yeah You don't want to ruin the embargo. Okay For a scientific meeting, we'll see. We'll try and get as. Would not be a weapon Much out there. Would not be a weapon embargo. No. We'll wait for a scientific meeting. Okay. Certainly, positive, negative based on the hazard ratio. Yeah. Can we add a little more color? We'll have to see what precedents are and where we think we might present. Will you show the mutant or the wild type? We will because the reason that we will do that is because the way that the trial is written, those are analyzed independently. Yeah. You're right. It's kind of two top-line announcements. Mutant-Hit or didn't hit. Right Wild type hit or didn't hit. Okay, got it. Yeah. That most definitely will be in there, and obviously this is highly material to Olema. We would do the analysis and make sure we get our conclusions right, but then that's the kind of thing we would announce publicly. The details one would expect will come at a subsequent scientific meeting, medical meeting. I see, okay. Let's go to some of the. Fall. You asked, I wanted to make sure. We're still. Fall We're not yet. Maybe sometime in Q3. Yeah. Later in Q3, we'll be able to refine a little bit for everybody. I see, okay. I guess you're still waiting for these events to play out? It is event driven, right? Obviously enrollment's important, but really, we're not so much worried about enrollment, but that the event rate gives us. Yeah. The number of events required to trigger the statistical analysis. We need to have a little more observation time to get a sense of when that might occur. I see, okay. Let's go to some of the ASCO redo. There's a lot. Okay. Sure. Of redo there, a lot of very exciting year for breast cancer. I think the two very relevant presentations there were persevERA and VIKTORIA-1. One, let's just go do the VIKTORIA-1 one first. Okay. We'll save persevERA for- Okay A little later. The redo there, they have inavolisib, they have gedatolisib being developed, and that's sort of that second-line setting. Right. In both the PIK3CA mutant and then the wild type, and we saw the mutant at ASCO. Right. How do you think about that, just given the data that you saw now in that mutant group, how do you think that strategy, I mean, that regimen is going to change that second-line setting? Yeah. You guys have the OPERA-01, which is also going to be a monotherapy agent. Yeah. How would all that change? Right. I don't think it changes it much. Let's just talk about the standard of care right now. Obviously, the first line's pretty well set. It's ribo, unless you're one of the few patients in whom it's contraindicated, plus AI. That's the gold standard, obviously we're trying to displace the AI of that in OPERA-02. After you've progressed on that regimen, assuming you do, then it gets more interesting because it's a selection of different targeted therapies with endocrine therapy or endocrine therapy alone. Right? Endocrine therapy alone is OPERA-01. VIKTORIA-1 is targeted therapy plus endocrine therapy, but in that case, the most recent one was with PI3 kinase mutated. Yep. Some of it is dictated by mutational status of the tumor. In other cases, it's really just other factors like comorbidities and will the patients tolerate a more intensive regimen. Now, the objective is very simple. However you order these things, you want to put off chemotherapy as long as you can. There are usually multiple targeted agents given in that line of therapy. Really what order it's in is a physician and patient preference. The VIKTORIA-1 data, where that fits in is it will potentially give another option for the PI3 kinase mutated patients to consider. Now, right now, obviously there's alpelisib, which is the oldest, but right now what we hear is more patients get capivasertib because the diarrhea, which is the main side effect of that, is easier to manage and tolerate than the hyperglycemia and the rash that comes with alpelisib. The question is, are physicians and patients wanting to get a weekly IV regimen? The fulvestrant is the same, so I don't think that's really different. Yeah Versus a daily oral regimen. I think that. Right Patients like oral. From the standpoint of sort of competitive space, if the gedatolisib regimen becomes really prevalent, then it doesn't actually compete with palazestrant, but it becomes another targeted agent with which we could combine. Right. It is given right now. Yeah With fulvestrant, it's always preferred to have a more active agent and to not have those injections. Right. With that said, GETA is being studied in that VIKTORIA II trial in that first-line setting. Yeah Also could challenge the standard of care there. How do you think about that regimen moving up as a triplet in that setting? Does it make sense for pala, I think you mentioned potentially combining with gedatolisib. Does it make sense to start exploring that opportunity? I think I'd rather see what happens in terms of practice patterns than to say what's exploring the opportunity. I would say in the first-line setting, I don't think the stomatitis, the mouthwash, and the IV infusions. Yeah Are going to be viewed as very attractive? Right Compared to what is considered a relatively easy to take, well-tolerated. Yep CDK4/6 plus AI or potentially something like palazestrant. Again, remember, in either case, you're talking about two oral daily medications with the. Yeah CDK4/6 and the endocrine agent, be it AI or for instance, palazestrant. Yeah If tamoxifen is successful- Right SERENA-4 is another one that's out there playing. I just don't think IV in that setting is really going to be very attractive. I see. Is it just the IV or is it like a triplet, just not I mean, if you're- I think if a triplet were. If the quality of life were, and IV here is a quality of life issue- Yeah As is the stomatitis. I think if it were well-tolerated and it didn't disrupt life like IV daily- Yeah I think more efficacy would be attractive- Right To patients to have a triplet. On the other hand I do think that there are liabilities that are hard to overcome. Right. Okay. Got it. You guys presented the phase II PALA-RIBO study a year ago, and it showed very impressive 14 months in all patients and 13 months in patients after CDK4/6 use. These were, to me, they look very competitive- Yeah Compared to what VIKTORIA showed, either with the wild type or the mutant population. Why not just given that- Yeah Why not do a phase III combination with ribo in a second line setting? That way, you don't have to worry about- Yep ESR1 mutant or wild type. It's going to be all comers. No, you're at a very good point. I'll explain it in two ways. I certainly agree with you that the data is very compelling, and it was compelling in the mutant and the wild type subsets. Here's the thing, and we know, for instance, that the prescribers give CDK4/6 after CDK4/6, that is a common existing practice pattern. Now it's somewhat fulvestrant, but pala has, certainly if it has more efficacy, but also then has the daily oral convenience. The one thing they don't like to do is they like to switch the CDK4/6. While that data's compelling, and some of it is post-ribo, patients and oncologists tend to like to switch the CDK4/6 if they've progressed on it. Almost all the patients are getting ribo now in the first line, right? Ribo after ribo is less attractive. I think we're thinking about do we want to do a combination in the second, third line setting? Yeah. If so, it's probably not ribociclib because of the first line use. You leave it up for physician choice. There are multiple ways to do it. Yeah. The thing right now where we are is it's probably useful to see how OPERA-01 reads out. Mm-hmm. I see. It's not that far off. Right. I see. Okay. Yeah. Sort of let that lead the way in terms of the label. Yeah. If we get the wild type there, that sets obviously a very different situation. Yeah, sure. Yeah. sure. Yeah. It's very differentiated. I think we can sit down with a more full picture in mind. Yep About what do we want to achieve with combination in that setting. Got it. It is absolutely true that there are physicians and patients who say, "Geez, I'm not ready to take just a monotherapy now. I want to get a targeted agent. I want to get the most active things I can." You want to be able to provide both. Right. Okay. Let's move on to persevERA. That's another big trial. Yep. A lot to redo from that. Me and you discussed this trial many times well ahead of ASCO, and I was fairly bearish about how this trial would read out. On day one when lidERA read out, we put out a note saying that I see high risk for persevERA. We finally saw the full presentation at ASCO. What is your overall impression, and is there any concern to OPERA-02? My overall impression, the trial was negative. Yeah. That's absolutely true. In terms of its hazard ratio of 0.89x did not achieve statistical significance. On the other hand, there's very clear evidence of activity. In other words, the underlying hypothesis of these first-line therapies, persevERA, but also OPERA-02, is that aromatase inhibitors are not completely suppressing the growth and proliferation signal from the estrogen receptor, and that you can do better by hitting the receptor harder with a complete antagonist, and ideally by doing that with a higher exposure where you completely shut off the receptor all the time. I believe that giredestrant's lower exposure probably was a liability there. Even so, they had five months delta in median PFS. That is meaningful. Okay. It didn't hit statistical significance, but it's meaningful. I think where we have better phase II data than giredestrant had, it really reads through nicely to OPERA-02. In my opinion, it increases the probability of success of OPERA-02. On the other hand, you asked about things to learn or concerns. One thing that happened in persevERA that I think is hard for me to understand, but I think was definitely a liability, was they enrolled 10% of their patients were endocrine-resistant patients. Those patients didn't do well, and I think they would've diluted the treatment effect in the endocrine-sensitive patient population. We don't enroll any of those patients in OPERA-02. I should say SERENA-4 doesn't either. I think that's one thing we suspected you shouldn't do, but now it's confirmed. We didn't do it. There's another thing that's interesting to watch, which is that the control arm, palbo plus AI, outperformed historical a bit by about three months. That's normal in oncology. Over time, a regimen often gets better. Oncologists get better at giving these medications. I think we will want to look at that and ask ourselves, do we want to make any changes to OPERA-02 going forward? If SERENA-4 stays on time in the second half of 2026, we'll wait for that because then we'll have two data sets, and that's fine. If that gets pushed out, we might not be able to. I see, okay. I think when we also looked at that trial, besides the PFS sort of missing with that hazard ratio 0.89x that you mentioned and then the P value being 0.156x. Yes. I think the ORR, CR, PR, SD, CBR were basically identical between the treatment arm and the control arm. I agree with you, there's a five-month improvement, and I think in the past you guys called out that six months would be good. Yeah Would be statistically significant. Then you look at the Roche's plan, stats plan, where they were powered to 89% to show hazard ratio 0.77x. They set the threshold, the boundary for. Yeah For success at 0.85x. Yes. Do you agree with that statistical plan to begin with? Maybe I wanted to ask you that. What is your hazard ratio and powering assumption for OPERA-02? Yeah. We haven't discussed our plan for OPERA-02. The biggest reason for not discussing the plan is because if we see data from SERENA-4. Yeah We've already seen persevERA, we may change it. Oh, yeah. You don't go out and say something and then go change it. Six months is a slam dunk, right? It will change the practice pattern. Five months, if you were statistically significant, if you go ask the investigators, the breast cancer docs, they'll say, "Okay, six months if we see that, we change our practice pattern. Five months, yeah, that would be good, too." You get down to four, they start saying, "Well, tolerability." Definitely six months is clear. I go back to this plan. I really wonder, and we can't do it, but Roche could do it. They could remove those patients- Who were endocrine-resistant and say, "What does the curve look like? Yeah. I think it would separate earlier. The separation was then maintained. I really think that it's not necessarily the stats plan that I wonder about that trial. It's the inclusion criteria and the patients they studied. I think that trial design might have been perfectly fine if you didn't put on endocrine-resistant patients. Mm-hmm. I see. It's hard to tell because they. We didn't see. Well, they get 12 minutes, maybe down the road we will see it. No, we haven't seen that so far. You're right. Exactly. You mentioned about that control arm being a little higher than It was basically the same, I think same with that MONARCH-3, about 28 months. I think it was higher than the PALOMA-2. Yeah, by about three months. By about three months. Exactly. When you think about if the control arm is now, I think like what you said, with the modern day treatment, better care- Yeah That you're now going to see more of that higher end of that range. Do you believe that now you need more than six months to be statistical just because the control arm's stronger? No, it's not the more than six months, it's just that you change your statistical assumptions around how many events you need. Yep. Right? Obviously when you're doing something like that, you only want to do it once if you're going to do it, and you want to be as well-informed as you possibly can be. If there's a second trial that you can get, that would be huge. Yeah. What you do is you just go through and you calculate, okay, here's the irony, right? Hazard ratio is how the primary endpoint is done. Hazard ratio is how the trial stats plan is designed. Decisions about treatment are made by delta and medians. You are extrapolating from the one to the other. What you do is you just take the delta you're shooting for, you take what Hazard ratio you get, then you decide, how many patients do I need? How many events do I need? How long do I have to wait? Those would be the calculations. I see, okay. Okay, got it. I think you mentioned in the past that after looking at persevERA, you may go back and change the size of the study. Yeah. Is that still on the table that you guys are evaluating. Yep On the size? Okay. Based on that, if it's. We'd like to have SERENA-4, though, to complete that evaluation, right? We can do. You would wait for that. You're not. Yeah. No, you don't do these kinds of things twice. In particular, if, again, if, and I just take them at their word, if AstraZeneca is able to stick to their timeline of half two, we have time to use both. SERENA-4 is a larger study, you can see that. It's a larger study, which we like. The point is that the patient population is more appropriate to OPERA-02, like OPERA-02, SERENA-4 does not allow any endocrine-resistant patients on the trial. Right. Okay. Got it. Now, given that higher performance of that placebo arm. Yeah Due to the better care out there, how would increasing the size help mitigate some of this risk? Yeah, it does two things, right? Which is a six-month delta on top of a 25-month control arm and a six-month delta on top of a 28-month control arm have slightly different hazard ratios. That's the first thing you do, is you want to say, what hazard ratio am I trying to detect in order to see my clinically significant benefit? That obviously changes the stats plan, right? Because that's your primary endpoint. The second thing it does is it changes the time. Changes how long you need to wait to get the events you need. First of all, your event rate's slower because your control arm has- Yep Got a longer median. As well, you're kicking out what six months is. There's another calculation, which is how long does it take for the trial to mature? There are two ways to get those events, right? Wait longer- Or have more patients at risk. That is to say, more patients treated. You put both of those factors into the calculation. I see. Okay. Got it. You go to regulators, then you go to your steering committee, and it's a real process. Right. You look at the persevERA trial. I think you pointed out that 10% patient progress- Yes Right? There's other stuff to it, too. There is. I think the cap de novo disease, and then there's higher. OPERA-2, how is it defined differently that you think? What are other ways that you believe, besides that 10%? That's the main thing, actually. Yeah. I don't know why they capped de novo disease. That's interesting. It was a bit lower than you would see. Yeah. I don't know why they had more visceral disease. I didn't see anything that Roche did in its design or execution. Yeah That would cause that to happen. They stratified for them. In the control. Yeah. I don't know. You're right, it was a bit on the high side. Yeah. Again, these are aspects that I think with two data sets are things you look at and say, "Are we seeing a change in who gets enrolled in these trials, or is this an outlier versus what other trials have seen? Right. I see. SERENA-4 will be reading out probably could be around the same timeframe as OPERA-01. Could be. Is there any reason to believe that trial could succeed? If it doesn't succeed, what does it mean for you guys? Yeah. First of all, it doesn't succeed, it really doesn't mean anything for us. The control arm will still be interpretable. Yeah. It's palazestrant plus AI, and anastrozole in that case. Secondly, look, OPERA-02, you mentioned the data already, the long period of progression-free survival post CDK4/6 with ribociclib and palazestrant. Our trial is based on our data, our data, uncontrolled phase II looks better than the others have. I think it doesn't change our view of OPERA-02. In fact, as I said, persevERA gives us higher confidence because of the level of benefit they did see without demonstrating statistical significance. Your question was, could SERENA-4 be positive? It's interesting. I think if SERENA-4, without the endocrine-resistant patients with the higher N, with the same level of benefit, maybe could be positive, actually. Right. The concern I have is that camizestrant has the lowest exposure of all of these agents because of the tolerability. Is that enough or is it not? I see. Any learning from SERENA-6 because there was an updated presentation at ASCO, with the updated PFS-2. Is there anything there that you feel like you can apply to either SERENA-4 or OPERA-2? Nothing. Yeah. Nothing. Yeah. The learning is don't- Okay Do that trial. Fair enough. Okay. Let's spend the last two minutes on OPERA-01. Okay. That trial's reading out in fall. Yes. This is designed very differently from VERITAC-2. In some way, right? Even though you guys both follow the EMERALD design. One big difference was that you guys allow prior fulvestrant. We did. Also adjuvant therapies, where VERITAC-2 did not. As you think about some of these differences that could either benefit or not benefit OPERA-01, how do you think about that compared to VERITAC-2 now after you see that data? Yeah. Do you think you made the right choice to allow fulvestrant and also adjuvant use? I do, and the reason I say that is because I think that more mimics the standard of care. You're absolutely right that we're different from VERITAC-2. We're much more similar to EMERALD Yeah In that respect. We do have some differences. We didn't allow prior chemotherapy, EMERALD did. We require six months on your prior endocrine regimen before you get on the trial, and there was no limitation on that in EMERALD. We feel like EMERALD was the right trial. In this patient population, it best mimic the practice pattern that we're seeing. Yeah. You control for some of these things, right? You stratify by if they had fulvestrant or not. Right. You do things to make sure you're equally distributed. Right. We really felt like EMERALD was very informative. I see. Okay. Final question for you. Your confidence level in that ESR1 wild type, if you don't succeed, what does it mean for pala in that second-line setting? What does it mean for OPERA-01? Do you much need it to succeed? I don't think we need it to succeed. I think that there's a way to differentiate just in the mutant, potentially. By having more than two months extension of PFS, That would be quite meaningful. I don't mean to downplay it. Yeah. It is a really meaningful differentiator. Sure if we're able to get it. Absolutely. We saw 5.5 months in the wild type in our phase II setting. If we can recapitulate that, obviously uncontrolled, error bars, everything. If we can recapitulate that, it should be compelling, and then that gives a group of patients who currently have an unmet need that's unaddressed, a treatment option. The trial is well-designed to address that question. Fantastic. Thank you so much. Thank you. It's been a pleasure hosting you. Always an interesting discussion. I'll turn it to you for final remarks. Yeah. It's a busy year for Olema and for this space, and we look forward to our first phase III trial readout in the fall, to updating on KAT6 with combos as soon as we can, with palazestrant and fulvestrant. OPERA-02 is enrolling well, so great opportunity in the first-line setting, I think supported by the data we've seen recently. Great. Thanks a lot, Sean. Thank you.