Olema Pharmaceuticals, Inc. ($OLMA)

All right. Let's kick off the next session. Good afternoon, everyone. It is my pleasure to be hosting Olema Oncology and Sean Bohen, CEO of the company. Sean, welcome.

Thank you, Rich.

Glad to be hosting you for another year at the GS Conference. Before I -- we have a lot to talk about. 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-positive/HER2-negative breast cancer. This is the most common malignancy in women. It's the second most common cause of cancer death and ER-positive/HER2-negative 70% of it. And we have 2 clinical stage assets. The first is palazestrant, which is in 2 Phase, three programs ongoing. The first readout, as we will talk about, to be in the fall from OPERA-01 or monotherapy. And then we recently presented data on our KAT6/7 inhibitor at ASCO showing monotherapy activity, both in ER-positive/HER2-negative breast and also castration-resistant prostate cancer. And the combinations are ongoing for breast and to be started for prostate cancer with that molecule.

Great. And can you remind us of the cash position you guys have, the runway guidance and what does it include that not include?

Yes. So at the end of Q1, we had about $505 million, just a little worth of $0.5 billion on our balance sheet. That will take us nicely into the second half of 2028. And 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, but also to start commercialization.

I see. Okay. Fantastic. Do you guys -- let's kick it off with the KAT6, because you guys presented that data at ASCO. So what are the key highlights there?

The key highlight here, this is so 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 3 histologies, that allowed ER-positive/HER2-negative breast, where KAT6 is 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, so not really much data there. But we saw single-agent antitumor activity in ER-positive/HER2-negative 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. But we saw less cytopenias than at a similar phase what Pfizer saw. So in breast cancer, we saw 22% Grade 3 neutropenia, which is about half of what Pfizer saw. So 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. And we recently signed a supply agreement in collaboration with Bayer to combine with their androgen receptor inhibitor, NUBEQA.

Right. So 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 as we might be able to have some, particularly from fulvestrant. Fulvestrant is only one dose level behind monotherapy by the end of the year, certainly first half of next year.

Okay. So given that we only see the monotherapy.

That's right.

And then I think for Pfizer, we've seen their monotherapy data. We see some combination data.

Yes.

But it's hard to kind of compare the monotherapy data set, because it's hard to know what the follow-up period is when you look it.

Yes.

I mean, is that a fair statement?

Yes.

It's still too early to know how like from a safety perspective. But we have seen from the Pfizer's KAT6 program that they have the data -- the combination data, I think they have like with fulvestrant with the 2 different dose levels. And we have seen what that looks like from a grade 3 neutropenia perspective. So really to compare -- you have to really compare the combination, right, because of the more -- 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's important that there's not as much follow-up because this is primarily a cytostatic, not a cytotoxic mechanism. And so it does sometimes take -- we saw it in our data set, but certainly, Pfizer saw that patients responded over time. And so more follow-up can be useful. But I think that we have less, neutropenia is probably pretty certain. We also don't see dose dependence of neutropenia. They did see dose dependence of neutropenia. So I think by dialing out KAT5 and 8, we may have created a different tolerability profile. 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.

Right. Okay. Got it. And also, like does it make sense to think about the KAT6? I know the combination is just a KAT 6 plus Pala or fulvestrant. Does it make sense to do -- to think about a KAT6 plus Pala plus CDK4/6 in that setting. Or am I jumping the gun?

Yes. No, you're not jumping the gun. I think we do need more tolerability data. The reason I say you're not jumping the gun it's actually written into the protocol. So we've that option already. So yes. So it's not to bring up something that we had anticipated. With the dependency as everyone knows, CDK4/6 inhibitors are primary AE is neutropenia. And so 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, right. Because that -- I mean, when we first looked at Pala, Pala has higher neutropenia than other SERDs. But when you combine it, you don't see that additive effect. That's an interesting observation.

It's exactly right. So we've a kind of mid-single-digit rate of neutropenia. Most patients with a pause are able to continue on the therapy, sometimes at a lower dose. But I think the big concern that primarily investors had, well, when you combine with CDK4/6 is, are you going to exacerbate this thing? And remember, our first CDK4/6 we combined with is the one that causes the most, which is palbociclib (IBRANCE). And there was no enhancement we've seen that as well.

So that was interesting. So I've an idea. I've been thinking about this even before ASCO and can't wait to ask you this. Have you thought about the possibility of going to like the first line with just KAT6 and Pala and just get CDK4/6 altogether? Because in case there is an overlapping toxicity between KAT6 and CDK4/6, why not -- I mean, why not just go KAT6 and Pala? Do you have to have CDK4/6?

I don't want to -- I'm thinking from a regulatory standpoint. I won't do that right now. Let's just think about it from an efficacy standpoint. I think if the Pala combo data, which initially will be in post-CDK4/6 treated patients, 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. And I think that's a pretty straightforward thing, if the tolerability is adequate. It has to be...

If not?

Yes. If not, I think it depends upon the efficacy we see in that post-CDK4/6 setting. And then I do think we've to think about what would be the regulatory pathway because we won't have OPERA-02 data yet, if we were to do that. So I'd have to think about the regulatory pathway.

Right. And it would be 2 novel agents.

That's what I'm worried about. That's exactly.

But then by the time you would kick that study off, Pala would have been approved.

Potentially by OPERA-01 in the second or third line setting.

Yes. Yes. Okay. And you also showed KAT6 in that NSCLC and CRPC. What's the development plan now looking at like these 2 new areas? You guys have been traditionally focused on breast cancer now. 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-positive/HER2-negative breast cancer. And that certainly is the case with KAT6. But we've also said that, that's not how cancer works. Cancer pathways -- the signaling pathways that contribute to evolution of cancer are often used in multiple cancer types. And that's the case here for KAT6. And so preclinical data said castration-resistant prostate and non-small cell lung. We only got one lung cancer patient. So we really don't very much to say that. We got 10 prostate cancer patients, most of whom were treated with prior chemo and/or prior radioimmunotherapy, and we saw clear antitumor activity. So our next step there is to expand in Phase Ib2 with NUBEQA in the castration-resistant prostate setting. And I think it's 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 and the standard of care is very complicated. But now that we have a path forward in other histologies, it might be worthwhile.

Okay. Got it. And how is the OPERA-01, OPERA-02 trials going? Remind us when should we see data? I know you said fall or early fall, late fall. Like how do you -- how should we think about it? And also for OPERA-01, what data will you present? Like what -- is there any of this data that you think is mature enough to present?

Yes. So the OPERA-01 is going very well. It's certainly on target, and we're reiterating the top line data in the fall. I anticipate that, that will be a top line press release, right, sort of it hit. It didn't. I don't -- beyond that, it depends on -- you don't want to ruin the embargo for a scientific meaning. So we'll see -- we'll try and get as much out there. No, no, no, no. We'll wait for a scientific meaning. But certainly, positive, negative based on hazard ratio. Can we add a little more color? We'll have to see what precedents are and where we think we might present.

Or 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. So you're right. It's kind of 2 top line announcements. Mutant hit or didn't hit. Wild-type hit or didn't hit. Yes. So that most definitely will be in there. And obviously, this's highly material to Olema. So we would do the analysis, 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 medical meeting.

I see. Okay. So let's go to some of the readout.

In fall. Fall was the you asked -- I wanted to make sure -- we're still reiterating not yet. Maybe in sometime in Q3, later in Q3, we'll be able to refine a little bit for everybody.

I see okay. So I guess you're still waiting for like these events to play out.

It's event-driven, right? So obviously, enrollment is important, but really, we're not so much worried about enrollment, but that the event rate gives us the number of events required to trigger the statistical analysis. And so we need to have a little more observation time to get a sense of when that might occur.

I see, okay. So let's go to some of the ASCO redo. There's a lot of redo there, a lot of very exciting year for breast cancer. So I think the 2 very relevant presentations there were persevERA and VIKTORIA-1. Let's just go do the VIKTORIA-1 first. We have a lot -- we'll say persevERA a little later. So the redo there, they have Celcuity, they have data being developed in that sort of a second-line setting in both the PIK3 mutant and then the wild-type, and we saw the mutant at ASCO. 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? You guys have the OPERA-01, which is also going to be a monotherapy agent. How would all that change?

Right. So I don't think it changes it much. So let's just talk about the standard of care right now. Obviously, the first line is 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. And 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 or with endocrine therapy or endocrine therapy alone, right? So endocrine therapy alone is OPERA-01. VIKTORIA is targeted therapy plus endocrine therapy. But in that case, the most recent one was with PI3 kinase mutated. So 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. So there are usually multiple targeted agents given in that line of therapy. So really, what order it's a physician and patient preference. The VIKTORIA data where that fits in is it would 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 palbociclib, because the diarrhea, which is the main side effect of that's easier to manage and tolerate than the hyperglycemia and the rash that comes with alpelisib. So 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 versus a daily oral regimen. And I think that -- I think patients like oral. From the standpoint of sort of competitive space, if the geda regimen becomes really prevalent, then it doesn't actually compete with palazestrant, but it becomes another targeted agent with which we could combine, because it's given right now with fulvestrant, but it would be -- it's always preferred to have a more active agent and to not have those injections.

Right, right. I mean with that said, I mean, geda is being studied in that VIKTORIA-2 trial in that first-line setting and also could challenge the standard of care there. How do you think about sort of that regimen moving up as a triplet in that setting? And then also, does it make sense for Pala 2, I think you mentioned potentially combining with geda. Does it make sense to start exploring those -- that opportunity?

I mean I think you'd rather see what happens in terms of practice patterns 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 are going to be viewed as very attractive compared to what is considered a relatively easy to take well-tolerated CDK4/6 plus AI or potentially something like palazestrant. But again, remember, in either case, you're talking about 2 oral daily medications with the CDK4/6 and the endocrine agent, be it AI or for instance, palazestrant or if camizestrant is successful, SERENA-4 is another one that's out there playing. So 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 don't think -- I think of a triplet where if the quality of life were -- and IV here is a quality of life issue as is the stomatitis. I think if it well tolerated and it didn't disrupt life like IV daily, I think more efficacy will be attractive to patients to have a triplet. On the other hand, I do think that there are liabilities that are quite over.

Got it. Okay. 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. So these were, to me, like they look very competitive compared to what VIKTORIA showed either with the wild-type or the mutant population. So why not just given that, why not do a Phase III combination with Ribo in the second-line setting? That way, like you don't have to worry about ESR1 mutant or wild-type. I mean just is it going to be all covers?

No, it's a very good point. So I'll explain it in 2 ways. I certainly agree with you that the data is very compelling, and it was a compelling in the mutant and the wild-type subsets. Here's the thing -- and we know for instance, that prescribers gave CDK4/6 after CDK4/6, that's a common existing practice pattern. Now it's done with fulvestrant, but Pala has -- certainly, if it has more efficacy, but also then it has the daily oral convenience. The one thing they don't like to do is they like to switch the CDK4/6. And so while that data is 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. And almost all patients are getting Ribo now in the first line, right? So Ribo after Ribo is less attractive. So I think we're thinking about do we want to do a combination in the second and third-line setting? And if so, it's probably not ribociclib because of the first line.

You leave it up for physician choice.

There are multiple ways to do it. The thing right now where we are it's probably useful to see how OPERA-01 reads out. It's not that far off.

Right. I see. Okay. So sort of let that lead the way in terms of the fulvestrant.

Yes. And then if we get the wild-type there, that sets obviously a very different situation. It's very differentiated. And then I think we can sit down with a different -- with a more full picture in mind about what do we want to achieve with combination in that setting. It is absolutely true that there are physicians and patients who say, "Geez, I don't want -- I'm not ready to take just a monotherapy now. I want to get a targeted agent. Do I want to get the most active things I can. And so you want to be able to provide both.

Right, right. Okay. So let's move on to persevERA. That's another big trial, a lot of redo from that. So 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 1 when lidERA read out, I was -- we put a notes saying that I see high risk for persevERA. So we finally saw the full presentation at ASCO. What is your overall impression? And is there any concern to OPERA-02?

Yes. So my overall the trial was negative. That's absolutely true. In terms of its hazard ratio of 0.89 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 lower exposure probably was a liability there. But even so, they had 5 months delta in median PFS. That's meaningful. It didn't hit statistical significance, but it's meaningful. And so I think where we have better Phase II data than giredestrant had, it really reads through nicely to OPERA-02. My opinion, it increases the probability of success of OPERA-02. Now 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 it was definitely a liability was they enrolled 10% of their patients were endocrine-resistant patients. And those patients didn't do well. And I think they would have deleted -- I'm sorry, diluted the treatment effect in the endocrine-sensitive patient population. Now we don't enroll any of those patients in OPERA-02. I should say SERENA-4 doesn't either. So I think that's one thing we suspected you shouldn't do, but now it's confirmed. Now 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 3 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. Now we won't -- if SERENA-4 stays on time in the second half of 2026, we'll wait for that because then we'll have 2 data sets, and that's fine. But if that gets pushed out, we might not be able to.

I see. Okay. Yes. So I think when we also looked at that trial, besides the PFS sort of missing with that hazard ratio of 0.89 that you mentioned and then the p-value being 0.156. I think the ORR, CR, PR, SD, CBR were basically identical between the treatment arm and the control arm. So I agree with you, there's a 5-month improvement. And I think in the past, you guys called out that 6 months would be static. And then you look at the Roche's plan that stats plan where they were powered to like 89% to show hazard ratio of 0.77, but then they set the threshold -- the boundary for success at 0.85. I mean, do you agree with that statical plan to begin with? Maybe I just wanted to just ask you that. And what is sort of your hazard ratio and powering assumption for OPERA-02.

Yes. So 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, we've already seen persevERA, we may change it. So you don't go out and say something and then go change it. But we do -- so 6 months is a slam dunk, right? It will change the practice pattern. Five months, if you were statistically significant, would be -- if you go ask the investigators, the breast cancer docs, they'll say, okay, 6 months, if we see that, we change our practice pattern 5 months. Yes, that would be good, too. You get down to 4, they start saying, well, tolerability. So definitely, 6 months is clear. I go back to this plan. I really wonder -- and we can't do it, but Roche's could do it. They could remove those patients who were endocrine resistant and say, what does the curve look like? And I think it would separate earlier. The separation was then maintained. So I really think that it's not necessarily the stats plan that I wonder about that trial. It's the inclusion criteria in the patients they studied. I think that trial design might have been perfectly fine, if you didn't put on endocrine-resistant patients.

I see. Yes, it's hard to tell because they never -- we didn't see...

Well, yes, they get 12 minutes. So maybe down the road, we will see it. But now, we haven't seen that so far. You're right.

Yes, exactly. So you mentioned about that control arm being a little higher than sort of -- it was basically the same. I think same with that MONARCH 3, about 28 months. I think it was higher than the PALOMA-2...

Yes, by about 3 months.

By about 3 months. Exactly. So -- but when you think about sort of if the control arm is now, I think like what you said with the modern-day treatment, better care that you're now going to see more of that higher or higher end of that range. Do you believe that now you need more than 6 months to be static just because the control arm is stronger?

No, it's not the more than 6 months. It's just that you change your statistical assumptions around how many events you need, right? And so -- and 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. So if there's a second trial that you can get, that would be huge. But 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. So you are kind of extrapolating from the one to the other. And what you do is you just take the delta you're shooting for, you take what hazard ratio you get and then you decide how many patients do I need, how many events do I need? How long do I have to wait? And those would be the calculations.

I see okay. Okay. Got it. So I think you mentioned in the past that after looking at persevERA, you may go back and change the size of the study. Is that still on the table that you guys are evaluating on the side? Okay. So based on that, how -- I mean...

We'd like to have SERENA-4 though to complete that evaluation.

We should just wait for that. You're not.

Yes, yes. No, you don't do these kinds of things twice. In particular, if -- again, if -- and I'd just take them at their word, if AstraZeneca is able to stick to their time line of half 2, we have time to use both.

Because SERENA-4 is a larger study, so you kind of see that.

It's a larger study, which we like, but the point is that the patient population is more appropriate to OPERA-02, because like OPERA-02, SERENA-4 does not allow any endocrine resistant patients on the trial.

Right. Okay. Got it. So now given that higher performance of that, that placebo arm into the better care out there. How would increasing the size would help mitigate some of this risk?

Yes, it does 2 things, right, which is a 6-month delta on top of a 25-month control arm and a 6-month delta on top of a 28-month control arm have slightly different hazard ratios. So 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. So 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 is slower because you're control arm has got a longer median. But then as well, you're kicking out what 6 months is. And so there's another calculation, which is how long does it take for the trial to mature. There are 2 ways to get those events, right? Wait longer or have more patients at risk. That is to say more patients treated. And so you put both of those factors into the calculation.

I see. Okay. Got it.

And then you go to regulators, then you go to the steering committee and it's a real process.

Right. So now you look at the persevERA trial, I think you pointed out that 10% patient progress, right. So there's other stuff to it, too. I think the de novo disease and then there's higher an alpha-2 -- how is it designed differently that you think? And what are other ways that you believe besides that 10%?

That's the main thing, actually. I don't know why they can't de novo disease. That's interesting. So it was a bit lower than you would see. I don't know why they had more visceral disease. I didn't see anything that Roche's did in its design or execution that would cause that to happen. They stratified for them. Yes. I don't know. It was -- you're right, it was a bit on the high side. So again, these are aspects that I think with 2 data sets are kind of 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 obtained.

I see. So SERENA-4 will be reading out probably could be around the same time frame as OPERA-01.

Could be.

How do you -- is there any reason to believe that trial could succeed? And then if it doesn't succeed, what does it mean for you guys?

Yes. I think -- so first of all, it doesn't succeed, it really doesn't mean anything for us. The control arm will still be interpretable. It's palbo plus AI and Letrozole in that case. Secondly, look, OPERA-02, and 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. And our data uncontrolled Phase II looks better than the others have. And so 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 end with the same level of benefit maybe could be positive actually. The concern I have is that camizestrant has the lowest exposure of all of these agents, because of the tolerability profile. Is that enough or is it not? The...

I see. Any learning from SERENA-6, because that was -- there was an updated presentation at ASCO with the updated PFS2. Is there anything there that you feel like you can apply to either SERENA-4 or OPERA-02?

Nothing. Nothing. Yes. Yes, the learning is don't do that.

Fair enough. Okay. Let's spend the last 2 minutes on OPERA-01 trials reading out in fall. This's very -- designed very differently from VERITAC-2 in some way, right, even though you guys both follow the EMERALD data. So one big difference is that you guys allow prior fulvestrant and then also adjuvant therapies where VERITAC-2 did not. So 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 now after you see that data? Do you think you made the right choice to not allow -- sorry, 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. It also -- you're absolutely right that we're different than VERITAC-2. We're much more similar to EMERALD in that respect. So we do have some differences. We didn't allow prior chemotherapy. EMERALD did. We require 6 months on your prior endocrine regimen before you get on the trial, and there was no limitation on that in EMERALD. But we feel like EMERALD was the right trial. It was in this patient population, it was best mimic the practice pattern that we're seeing. Now you control for some of these things, right? You stratify by if they had fulvestrant or not, you do things to make sure you're equally distributed. But 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 must 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 2 months extension of PFS, and that would be quite meaningful. It is -- I don't mean to downplay. It is a really meaningful differentiator if we're able to get it. 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 are 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.

Pleasure hosting you. Always an interesting discussion. And I'll turn it to you for final remarks.

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. And OPERA-02 is enrolling well. So a great opportunity in the first-line setting, I think, supported by the data we've seen recently.

Great. Thanks so much.

Thank you.