Olema Pharmaceuticals, Inc. Common Stock Citigroup’s Biopharma Back to School Summit 2026

There's several things. Yeah. Thank you, Yigal, and thanks to both of you for attending.

Obviously our lead asset is palazestrant. It's a complete estrogen receptor antagonist for the treatment of ER-positive, HER2-negative breast cancer, and we're studying it in phase III in two contexts. One is as a monotherapy, in the second third line settings. These are patients who've progressed on a prior CDK4/6 plus an AI, now going on to another therapy. The control arm is fulvestrant or exemestane. Experimental arm is single agent palazestrant. That trial is finished enrollment and randomization. We're awaiting readout, and we forecast that we will have our top-line data in Q1. In that population, as you know, it's very interesting because it's really two separate groups. There are those individuals who progressed on their prior therapy with an ESR1 activating mutation. It's about 40%-50%. The remainder still have estrogen receptor in the wild-type form and is not mutated.

There's been prior success in the mutant population, but no one's been able to do better than fulvestrant or exemestane in the wild type. We're testing both of those populations, both of those hypotheses in the trial. In total, it's about a $5 billion a year market opportunity. For us, very significant. The other trial that's ongoing and enrolling very well is in the first-line setting, and in that case, we are combining with the gold standard CDK4/6 inhibitor, which is KISQALI. That trial is called OPERA-02. The control arm is KISQALI plus letrozole and AI. Experimental arm is KISQALI plus palazestrant. It's enrolling very well. It'll take a couple years to read out just because of the effectiveness of that treatment.

But that's a $10 billion plus market opportunity, should we be able to access it. Both of those trials are based on phase II data that suggests that we can do better than the existing therapies and have activity in these different settings we're describing.

First of all, the trial obviously is not a blinded trial, right? It's an open label trial. But the reading of the endpoint is blinded.

Right. It's a blinded, independent radiographic review.

Progression-free survival is the primary endpoint of both OPERA-01 and OPERA-02 trials. Yeah, we do blinded event rate, and so that's in there to some extent. Mostly the slight delay had to do with a slowing toward the end of enrollment in the enrollment of the ESR1 mutated subset of patients. We think, we're not 100% sure, we think from our investigators that that might have been related to greater availability of ORSERDU in Europe. But again, it's past us. We are completely enrolled in the trial. We did not compromise the number of patients in either population, so it's fully powered for the statistical plan. I think the other important part about this is that overall, we had predicted 40%-50% of patients would be ESR1 mutated. We actually did end up in our predicted range.

I think that part isn't different. It's just that we were in the higher percentage earlier on, and it sort of fell a little bit toward the end.

Something in that range, yes. I'll go into what molecularly we think might be going on, but I think the strongest evidence is our phase II data, right? The question is obviously can you replicate that in the phase III setting? In the phase II setting, post prior CDK4/6, in that case, a little more heavily pre-treated patients because a significant number had had prior chemo that's not allowed at OPERA-01. We saw over seven months, median PFS in the mutant setting, 5.5 in the wild-type setting. That is better than anyone has been able to see in either of those settings, but certainly in the wild type. The bar in wild type is to extend PFS by about two months, right?

Lilly got approved with the ORSERDU at 1.7, which is probably a little on the edge, but it did lead to approval, but you'd say about two months. Recognizing that the control arm really should be two to three months, if we can replicate that five-month range, we should be able to access that population, and that's what's being tested in OPERA-01. Why might that happen when others haven't been able to do that? Well, in addition to being a complete antagonist, we have very high exposure, 14-day half-life, and a very high steady-state exposure compared to other drugs. We think that that is important in the context of maximizing the benefit you would get.