Oric Pharmaceuticals, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

Sure. Happy to, Frank, and thanks for having us. ORIC Pharmaceuticals. ORIC stands for Overcoming Resistance in Cancer. In a nutshell, that is the mission of the company. We are today focused on executing across two late-stage development programs. rinzimetostat, which is a PRC2 inhibitor that is being developed in prostate cancer in combination with two of the big three androgen receptor inhibitors in prostate cancer. That has just started its first Phase III study, a study called Himalayas-1, which is in the castration-resistant prostate cancer setting in patients who are post abiraterone. I am sure we will talk a lot about that today. Then our second program, enozertinib, which is a brain-penetrant TKI for lung cancer, which is being developed in two different populations within the EGFR family of mutations. EGFR exon 20, and then separately, EGFR atypical mutations.

That is a program that will have a pretty substantial data update coming up not too far from now in ESMO in Madrid in about a month's time. If all goes according to plan there, and we continue to show a best-in-class profile for that program, we would anticipate starting the first Phase III study next year in 2027. A lot going on at the company and extremely well-funded. Let us get into your specific questions.

Yeah. So probably the most common question we get in meetings these days is about Pfizer's data, and what is the expectations for MEVPRO-1. I always hesitate to comment on expectations for another company's program. Maybe what I will just leave it at is, I think we and others on the street have been doing a statistical events analysis around Pfizer's MEVPRO-1 study. That is the first of three phase III studies that Pfizer is undertaking with the same mechanism. Pfizer has got a drug, mevrometostat, which is a PRC2 inhibitor, which they are combining with the third of the AR inhibitors. I mentioned that we are combining our drug with two of the three big AR inhibitors. Pfizer is combining their drug with enzalutamide, which is their AR inhibitor that they acquired from Medivation.

They have got MEV-Pro01, MEV-Pro02, and MEV-Pro03, and MEV-Pro01 and MEV-Pro02 are in the CRPC setting, MEV-Pro03 is in the CSPC setting. MEV-Pro01 is the one that Pfizer recently, on their Q2 earnings call, narrowed the guidance for the top-line readout to Q4 of this year. I think that the analysis that we and others on the street are doing essentially suggests that probably bodes well for the trial results. The fact that the top line would be coming in Q4 probably means that the treatment arm is doing well and that the events have been accruing on the control arm. I think folks are now reading statistically a decent chance that that trial will be positive. Obviously, the later, the better in terms of that positivity.

But I think most importantly, Frank, is that almost any statistical analysis you can do on the event accrual into that trial would suggest that a readout in Q4 pretty much takes off the table a huge miss in the trial. Meaning that as you start to think about scenarios for how that trial might play out, whether that is a huge win ranging all the way down to a small win, a small miss, or a huge miss, you basically have taken a huge miss off the table at this point and narrowed the range of outcomes for them.

Okay. But beyond that, I will leave it to Pfizer to comment on expectations.

Yeah. If I just take those four scenarios again that any trial could have, which is a huge win, a small win, a small miss, or a huge miss. The fact that you have taken huge miss off the table, at least statistically speaking, should be a good thing because a huge miss obviously would call into question the mechanism of action itself. I think Yeah for all the statistical and event reasons that we have talked about, it seems highly unlikely that a huge miss is on the table at this point.

I think even beyond that, just taking a huge step back and looking at the half a dozen or so data points that at this point Pfizer has shown in various single-arm settings, as well as a randomized controlled trial of their own in a phase II setting, and then two different phase I data sets that ORIC has now presented. Another drug also had some positive data at ASCO GU. I think across half a dozen different data points, the mechanism does truly seem to be additive. When you add a PRC2 inhibitor with an androgen receptor inhibitor, you get pretty profound synergy.

Taking that big miss scenario off the table is quite helpful because I think the other three possibilities, which would be anywhere from a big win down to a narrow miss, would be, frankly, good for us. What I mean by that is, mechanistically, we have already seen evidence that this works. There is always edge case scenarios that can take place. If Pfizer has safety issues that pop up on the treatment arm, if that leads to dose reductions and therefore lower dose intensity that the patients receive, that obviously could compromise the therapeutic effect of their regimen. I mentioned that they are combining their PRC2 inhibitor with enzalutamide, which is their AR inhibitor. Enzalutamide is a well-known CYP inducer, meaning it pushes down the exposure of drugs that you try to combine with it.

They're having to dose higher with their mevrometostat in order to get back to the right exposures that can always insert some level of uncertainty into a trial. They're also taking a relatively, it's a new regimen, actually, that they're using in the phase III, which is dosing in a fed state as opposed to the randomized data where they were dosing in a fasted state. Now, they've shown data that suggests that they're able to exposure match between those two doses and regimens, but anything can happen in a phase III. There's a whole variety of reasons that could lead to an edge case scenario. But of course, everything that I just rattled off is very specific to their drug, to their regimen.

Yeah. Would not read through to rinzimetostat, our drug.