Oric Pharmaceuticals Stifel 2026 Healthcare Conference

mid-2027 as well. So we're looking to start our first Phase 3 study on the atypical patient population in the first half of next year. So look forward to next year, we should have 2 ongoing Phase 3 studies.

I think this is the first time I've ever heard you say we have 2 late-stage companies— yeah, studies going on.

So as has become expected, let's talk about MEPRO-1, which is actually not our drug, it's Pfizer's drug. So I guess taking a step back in our view on kind of the timeline shifts from Pfizer, I think taking a big step back is first and foremost, there's been a lot of datasets recently from Pfizer, from other competitors as well as ourselves that has shown the benefit of combining a PRC2 inhibitor with an AR inhibitor. I think the most compelling dataset that we've seen obviously is the randomized data we saw from Pfizer back at ASCO 2025. This is an 80-patient study. It was a randomized study. The treatment arm showed a 14.3-month benefit, PFS benefit. The control arm showed about a 6-month benefit. So pretty profound results in this patient population. This is post-abiraterone. Patients that could have seen up to 1 round of chemo. So from a high level, this is highly validated from a biological standpoint. Pfizer started their study MEPRO-1, which is in this exact patient population. It's a 600-patient study. They're showing the combination of mepro— mepro— meprometasone, I should say, in combination with enzalutamide versus a control arm of physician's choice between AR inhibitor and docetaxel.

They started this in late 2024. They had originally had their primary completion date as of, call it, mid-2026. So I think we were expecting it around that time. Since that, on their Q2 earnings call in early August, they shifted that guidance to Q3, Q4 of this year. And then on their Q3 earnings call, they just shifted it again to first quarter of next year. I think they said February of 2027. So At a high level, obviously it's a blinded study. We don't know any more than you guys do, but as you guys can imagine, a number of these street analysts, investors, as well as ourselves, we've done a lot of event-based modeling. To try to predict what these potential scenarios are relating to this delay. At a high level, we kind of looked at this in 4 quadrants, right? The big miss scenario, the slight miss, the slight win, and the big win. I think based on, again, all the data that we've seen so far with this mechanism, based on the event modeling we've done, I think we feel pretty comfortable that that big miss is very low probability, if not off the table.

So the small— there's always a possibility of a small miss, and obviously we don't know what that would be. We think, again, the biology makes a lot of sense. So if there is a miss, maybe it's regimen-related. Maybe that's something to do with their safety profile or high discontinuation rates. But in a scenario where there's a small win or a big win where the study is positive, obviously we think that's strong validation. for the mechanism, kind of a read-through to Rinzia as well.

Yeah, I mean, just to contextualize a little bit what the control arm could be capable in a study like this, you have ARPI switching, you have chemo.

It doesn't seem like anything in the control arm would warrant maybe 6 to 8 months. Do you think that's a fair assumption? Yeah, I think if you look at the— again, the control arm, just to clarify, is Enza or docetaxel. So if you look at kind of the benchmarks out there, I think you'll see docetaxel in this patient population will be, like she said, like 7 to 8 months. The AR inhibitor in the post-abecetin will probably give you 5 to 6 months. You know, we don't know what that distribution is. Assuming a 50/50 split, that gets you close to, you know, 6.75 or 7 months of duration. Could that inch up a little bit? That's possible as well. But we think kind of an outlier there would be unusual. Pfizer has said, I think on their Q2 earnings call, they kind of said they expect the control arm to be somewhere in the 5 to 8 month range. So obviously they're closest to the data.

That's kind of the latest data that we have. Matt, anything else you'd add to that? No, I think just, you know, the study has been delayed, so I think there's obviously multiple, you know, ways you could look at that. I think in general people have gotten comfortable Well, that might be a good signal. I think that's kind of what Pfizer's signaling. That's the way we interpret it as well. And I think just because the control arm of docetaxel ARPI switching has been so well studied in phase 3 studies, and it's been replicated in multiple studies by different parties that I think people generally feel good that enzalutamide switch should give you about a 5 to 6 month RPFS. Docetaxel in multiple phase 3 studies should give you 7 to 8. Anything within that range, I think Pfizer has signaled that is their expectation as well. And so again, if you kind of assume the control arm is doing what it should do, then we think, again, the study being delayed, so-called, than their expectations, due to less events occurring seems to be that could be driven by the treatment arm.

Yeah, I think, you know, one thing that's come up in conversations with investors recently that I think is very well appreciated by some and, you know, maybe not broadly enough is that both doctors and patients are going to be blinded to PSA levels.

You know, and some KOLs we talked to suggested that, you know, maybe PSA levels not budging or going up a bit in phase 1 were some of the reasons why, you know, studies like yours or Pfizer's in early stage have early drop-offs. Do you guys think this could maybe help out with a PFS-like endpoint or an RPFS-like endpoint?

Yeah, I think your point is a good one. I think in early prostate cancer studies like phase 1 studies, the primary endpoint of those studies are typically PK and safety. They're not blinded, so patients, physicians, investigators are aware of what the PSA response is, so for some reason if the PSA is not going down or it's up a little bit, they may just decide to come off the study. That is very different than what you see from an operational perspective in a phase 3 study. Where the patient and the doctor, the physician, is blinded to that information and all that information is done centrally, so they don't have that insight. You would expect that kind of discontinuation to kind of go away in a phase 3 study, and again, this isn't just applicable to Pfizer's dataset or our dataset. If you look across phase 1 studies in prostate cancer, you see this early discontinuation rate in these early studies for the reason you just articulated. So we do think that kind of— that risk goes away in the phase 3 setting.

Yeah, it was kind of interesting seeing that ESMO data for meprometastat monotherapy in that poster where there was almost no PSA response but 9-month PFS. talked internally about that or kind of trying to read into that. I know it was small patient numbers, but certainly a very interesting signal that I think was unexpected to many.

Yeah, I mean, Matt, you want to talk about the science behind the PSA? Yeah, in some ways it's not unexpected. You know, I would say the target and mechanism is different. So this is an area that we have spent at least the last 5 years understanding, trying to understand this mechanism the best we can, which is different than anything else in prostate cancer. It is an epigenetics target that basically you know, modifies gene regulation. One of the effects that we have seen preclinically, and now I think the Pfizer data kind of replicates this in the clinic, what it actually does is it increases KLK3 expression. which drives PSA responses. And so the way the mechanism works, a PRC2 inhibitor essentially reverses the resistance in prostate cancer cells. It will make a prostate cancer cell look more like an early-stage prostate cancer line. So with that, it actually increases AR signaling and things like that. We've kind of put out a lot of data within that, and so tend to, you know, what the Pfizer data show is actually you might actually see an increase in PSA as a single agent, and so again, somewhat of a confounder of that.

Usually other AR-directed therapies reduce PSA. I think a couple things with that, they still saw relatively long RPFS of almost 9 months as a single agent, which is actually a pretty good outcome. It's a small N and it's a single-arm study, but somewhat intriguing is just you can see that with just single agent. Where you really see the profound clinical or the profound synergies preclinically, and so I think this is, again, a lot of our data suggests this, others as well, is you see strong combination synergy preclinically when you combine a PRC2 inhibitor with an AR inhibitor, and so I think just the clinical data they have shown is basically replicating what you see preclinically. But, and it's something I think, you know, what we feel comfortable with within the Pfizer randomized data, the primary endpoint there was RPFS, which is the regulatory endpoint, and so, you know, I think a lot of people in prostate cancer therapies tend to look for PSA responses. It's an early surrogate endpoint. It doesn't have any regulatory bearing, but it's always interesting to see. It's just with our mechanism, there's confounding influences. So our mechanism hasn't really been driven by PSA responses.