Olema Pharmaceuticals, Inc. Q4 FY2024 Earnings Call

All right. Let's kick off the next session. Good afternoon, everyone. It is my pleasure to be hosting Olima Oncology and Sean Bowen, CEO of the company. Sean, welcome. Thank you, Rich. Glad to be hosting you for another year at the GS conference. Before, 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, Lima 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 two clinical stage assets. The first is palzestrin, which is in two phase three programs ongoing. Their 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 CAT-6-7 inhibitor at ASCO showing monotherapy activity both in ER-positive, HER2-negative breast, but 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 one-way guidance and what does it include? Yeah. So at the end of Q1, we had about $505 million, just a little north of a half a billion dollars 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 Kiskali in breast cancer, certainly the remainder of the Phase I-II for OP3-136, and also our efforts to file, assuming OPERA-01 is positive, on palzestrin, but also to start commercialization.

Okay, fantastic. You guys, let's kick it off with the CAT6 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 CAT6. The trial allowed three histologies. that allowed ER-positive HER2-negative breast, where CAT6 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, 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 dysgusia, 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 combination. The fulvestrant and the palvestrant 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 in Nubeca.

So when we look at the data, like you said, it's monotherapy only. There's no combo data yet. That's going to come potentially later on this year?

The optimistic is we might be able to have some, particularly from fulvestrin. Fulvestrin is only one dose level behind monotherapy by the end of the year, certainly for staff of next year.

Okay, so given that we only see the monotherapy data, and then I think for Pfizer, we've seen the monotherapy data, we see some combination data, 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 at it. Is that a fair statement? It's still too early to know how, like from a safety perspective. But we have seen from the Pfizer's CASTX program that they have that combination data. I think they have like with Fulvestrin, with the two different dose levels. And we have seen what that looks like from the grade three neutropenia perspective. So really to compare, you have to really compare the combination, right? because those are 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 is important that there isn't 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 CAT5 and 8, we may have created a different tolerability profile. I do think that for response rate and certainly response and 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 CAS6? I know the combination is just the CAS6 plus PALA or Fulvestrin. Does it make sense to think about a CAS6 plus PALA plus CDK4-6 in that? Or am I jumping the gun?

No, you aren't. You are not jumping the gun. I think we do need more tolerability data. And the reason I say you're not jumping the gun is it's actually written into the protocol. So we have that option already. So it's not something that we had anticipated. With the dependence, as everyone knows, CDK4-6 inhibitors are primary, but 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 Pella, Pella has higher neutropenia than other certs, but when you combine it, you don't see that additive effect. No, that's an interesting observation.

It's exactly right. So we have 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 was, well, when you combine with CDK4-6s, are you going to exacerbate this thing? And, you know, remember, our first CDK4-6 we combined with is the one that causes the most, which is palbociclib, iBrand, and there was no enhancement when we've seen that with iBrand as well.

So that was interesting. So I have 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 the first line with just CAS6 and Pellet and just skip CDK4-6 altogether? Because in case there is an overlapping toxicity between CAS6 and CDK4-6, why not just go CAS6 and Pellet? Do you have to have CDK4-6?

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 study? Now, obviously, if you can do it, then you have the opportunity for a triplet. And I think that's a pretty straightforward thing if the tolerability is adequate.

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 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 two novel agents.

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

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

Potentially by APRA 01 in the second, third line setting.

And you also show TAS-6 in that NSCLC and CRPC. What's the development plan now looking at this, like these two new areas? You know, 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-ponsored and fertility-negative breast cancer. And that certainly is the case with CAT6. But we've also said that, you know, 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 is the case here for CAT6. 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 have very much data. We got 10 prostate cancer patients, most of whom were treated with prior chemo and or prior radioimmunotherapy, and we saw clear anti-tumor activity. So our next step there is to expand in Phase I, B2 with Nubeca in the castration-resistant prostate setting, and 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, and the standard of carry 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 1, OPERA 2 trials going? Remind us, when should we see data? I know you said fall, is there early fall, late fall? How should we think about it? And also for OPERA 1, what data will you present? Is there any of this data that you think is mature enough to present?

Yeah, so the OPERO one is going very well. 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, right, sort of. It hit. Beyond that, it depends on you don't want to ruin the embargo for a scientific meeting. So we'll see. We'll try and get as much out there. No, no, no, no. We'll wait for a scientific meeting. But certainly positive, negative, based on the 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 two top-line announcements.

You know, mutant hit or didn't hit, wild-type hit or didn't hit. Okay, okay.

Yeah, so that most definitely will be in there. And obviously, this is highly material to Olimo, so 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. So let's go to some of the... And fall. Fall was the time you asked. I wanted to make sure.

We're still reiterating. We're not yet. Maybe sometime in Q3, later in Q3, we'll be able to refine a little bit for everybody.

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

It is event-driven, right? So obviously enrollment's important, but really we're not so much worried about enrollment, but 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 two very relevant presentations there were Persevera and Victoria, one. Let's just go to the Victoria one first. We have a lot of, we'll say Persevera a little later. So the redo there, they have CellQD, they have GETA being developed in that sort of second-line setting in both the PIC3 mutant and then the wild-type, and we saw the mutant at ASCO. How do you think about that, you know, just given the data that you saw now in that Milton group, how do you think that strategy, I mean, that regimen is going to change that second line setting? Because you guys have the OPRO one, which is also going to be a monotherapy agent. How would all that change?

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 OPERO2. 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? So endocrine therapy alone is OPERO1. Victoria 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 in is a physician and patient preference. The Victoria 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 alpalisib, which is the oldest, but right now what we hear is more patients get capivacertib because the diarrhea, which is the main side effect if that is easier to manage and tolerate than the hyperglycemia and the rash that comes with alpolicib. So the question is, are physicians and patients wanting to get a weekly IV regimen? The fulvestrin is the same, so I don't think that's really different, versus a daily oral regimen. And I think patients like oral. From the standpoint of sort of competitive space, If the GETA regimen becomes really prevalent, then it doesn't actually compete with palvestrant, but it becomes another targeted agent with which we could combine. Because it is given right now with palvestrant, but 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, GETA is being studied in that Victoria II trial in that first-time setting and also could challenge the center of care there. How do you think about sort of that regimen moving up as a triplet in that setting? And also, does it make sense for Pella to, I think you mentioned, potentially combining with Geta, does it make sense to start exploring that opportunity?

I mean, I think I'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 palizestrin. But again, remember, in either case, you're talking about two oral daily medications with the CDK4-6 and the endocrine agent, be it AI or, for instance, palizestrin or if camisestrin is successful in serena four is another another one that's out there playing so i just don't think ivy in that setting is really going to be very attractive i see is it is it just the ivy or is it like a triplet just not i don't think you know i think of a triplet where if it if the quality of life were and i'm ivy here is a quality of life issue as is the stomatitis i i think if it were well tolerated and it didn't disrupt life like id daily i think more efficacy would be attractive to patients to have a triplet um on the other hand um i do think that there are

liabilities that are right okay got it got it okay uh you guys presented the phase two pala arrival study a year ago and it showed very impressive 14 months uh in all patients and 13 months inpatient after CTK-46 use. So these were, to me, like, they look very competitive compared to what Victoria showed, either with the wild type or the mutant population. So why not just give that, why not do a phase three combination with RIPO in a second-line setting? That way, like, you don't have to worry about ESR-1 mutant or wild type. I mean, just, it's going to be all comers.

No, it's a very good point. So 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 that is a common existing practice pattern. Now it's done with fulvestrin, but, you know, 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 the 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, third line setting? If so, it's probably not ribocyclic because of the first line used. We can leave it up for physician choice. There are multiple ways to do it. The thing right now where we are is it's probably useful to see how OPER-01 reads out.

I see. It's not that far off. So sort of let that lead the way in terms of...

And then if we get the wild type there, that's obviously a very different situation. It's very differentiated. and then I think we can sit down 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 that we do 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 one when Ladera read out, we put a note 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 you offer to?

Yeah, so my overall impression, the trial was negative. That's absolutely true. In terms of its hazard ratio, 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 OPERO2, 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 gerodespirant's lower exposure probably was a liability there, but even so, they had five months delta in medium PFS. That is meaningful. It didn't hit statistical significance, but it's meaningful. And so I think where we have better phase two data than gerodestrin had, it really reads through nicely to OPERO2. In my opinion, it increases the probability of success of OPERO2. 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 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 diluted the treatment effect in the endocrine-sensitive patient population. Now, we don't enroll any of those patients in OPERO2. 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 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 OPERO2 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 two data sets and that's fine. But if that gets pushed out, we might not be able to.

So I think when we also looked at that trial, besides the PF that's sort of missing with that hazard ratio 0.89 that you mentioned and then the P value being 0.156. I think the OR, CR, PR, SD, CBR were basically identical between the treatment arm and the control arm. So 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, would be stats-sick. And then you look at the Roche's plan, that stats plan, where they were powered to like 89% to show has ratio 0.77, but then they set the threshold, the boundary for success at 0.85. I mean, do you agree with that plan to begin with? Maybe I just wanted to ask you that. And what is sort of your hazard ratio and powering assumption for Opera 2?

Yeah, so we haven't discussed our plan for Opera 2. 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. You don't go out and say something and then go change it. So six 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, 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. So 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? 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 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.

Yeah, it's hard to tell because they never show what they had.

Well, yeah, they get 12 minutes, so maybe down the road we will see it. But no, we haven't seen that so far.

Yeah, exactly. So you mentioned about that control arm being a little higher than the 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.

Yeah, by about three months.

By about three months, exactly. So, but when you think about sort of, you know, 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, higher end of that range. Do you believe that now you need more than six months to be static 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. 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. yeah um but what what you do is you just go through and you calculate okay here's the 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 median 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 size? Okay. So based on that, how, I mean...

We'd like to have Serena 4, though, to complete that evaluation, right? So you would wait for that.

You're not...

Yeah, yeah, 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.

Because Serena 4 is a larger study, so you can see that.

It's a larger study, which we like, but the point is that the patient population is more appropriate to opera O2 because like opera O2, Serena 4 does not allow any endocrine-resistant

patients on the trial. Right, right. Okay, got it. So now, given that high performance of that placebo arm into the better care out there, how would increasing the size would help

medication with 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. 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 benefits? So that obviously changes the stats plan, right? Because that's your primary endpoint. The second thing it does is it changes the time. It 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 got a longer median. But then, you know, as well, you're kicking out what six months is. And so 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 and so you put both of those factors into the calculation and then you go to regulators then you go to your steering committee and it's a real process

so now you look at the Persevera trial I think you pointed out that 10% patient progress so there's other stuff to it too the novel disease and then there's higher and opera too How is it designed differently that you think? What are other ways that you believe besides that 10%?

That's the main thing, actually. I don't know why they kept 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 did in its design or execution that would cause that to happen. They stratified for them. Yeah, I don't know. You're right. it was a bit on the high side. So again, these are aspects that I think with two 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? Right, I see. So Serena 4 will be reading out,

probably could be around the same time frame as Opera 1. Could be. How do you, is there any reason to believe that trial could succeed, and then if it doesn't succeed, what does that mean for

you guys? Yeah, 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, an astrosomal in that case. Secondly, look, OPERO2, and you mentioned the data already, the long period of progression-free survival post-CDK4-6 with ribocyclob and palazestrin. Our trial is based on our data, and our data, uncontrolled phase two, looks better than the others have. And so I think it doesn't change our view of OPERO2. In fact, as I said, Persevera gives us higher confidence because of the level of benefit they did see without demonstrating statistical significance. But 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 camazestrin has the lowest exposure of all of these agents because of the tolerability. Is that or is Is it not?

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. The learning is don't do that trial. Fair enough.

Okay, let's spend the last two minutes on Opera 1, that child's weeding out in fall. This is designed very differently from Veritech 2 in some way, right? Even though you guys both follow the Amarillo's design. So one big difference was that you guys allowed prior for restaurant and then also adjuvant therapies where Veritech 2 did not. So as you think about some of these differences that could either benefit or not benefit Opera 1, And, you know, how do you think about that compared to Veritec to now after you see that data? Do you think you made the right choice to not allow, sorry, to allow for veteran 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 know, you're absolutely right that we're different than Veritec, too. 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 six months on your prior endocrine regimen before you get on the trial and there was no limitation on that um and emerald but we feel like emerald was the right trial it was in this patient population it was the the best mimic the practice pattern that we're seeing now you control for some of these things right you you stratify by if they had full vestment 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 1? 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 two months extension of PFS, and that would be quite meaningful. I don't mean to downplay it. 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 two 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

design to address that question. Fantastic. Thank you so much. It's been a pleasure hosting you. Always an interesting discussion. And I'll turn it to you for final remarks.

Oh, it's a busy year for Olima and for this space. And we look forward to our first space retrial readout in the fall to updating on CAT 6 with combos as soon as we can with PALS Vestrant and Fulvestrant. And OPERO 2 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.