This train isn't even hit or rain. All right. Good afternoon, everyone. Thanks for joining us. We'll get started here with the next fireside. With us, we have ORIC Pharmaceuticals. From the company, we have Jacob Chacko, as well as CFO, Dominic Piscitelli. Gentlemen, thank you so much for joining us, and looking forward to the conversation.
Thanks for having us.
Excellent. Maybe just at a high level, and Jacob, if you want to give us the pitch on ORIC and what you guys are working on. I know you got two programs and got some very interesting data from a competitor that's going to read through to you guys later this year. Maybe just tee it up for us before we dig into the questions.
Sure thing. Happy to, Derek. At ORIC Pharmaceuticals, ORIC stands for Overcoming Resistance In Cancer. In a nutshell, that's the mission of the company. We have two late-stage programs, one for prostate cancer, one for lung cancer. Both are differentiated in their own ways versus the competitors that are out there. Both are either, say, in the case of rinzimetastat, our prostate program, it's already in its first phase III study, a study called Himalayas-1 in castration-resistant prostate cancer. I'm sure we'll get into some of the details of that. And then enozertinib, our lung cancer program, is, we think, headed towards its first phase III study, which would start next year. Both programs are going well in terms of development. We're well-funded with a healthy balance sheet, long cash runway. And let's dive into any specifics you'd like to discuss.
Excellent. Well, why don't we start? Pretty consequential readout for you guys in terms of the upcoming readout for Pfizer's MEVPRO-1 with mevrometostat. I guess, maybe discuss your expectations around that trial and particularly lighten their announcement in terms of the data's coming Q4, so now we know that. How does that read through to rinzimetastat? How does it read through to Himalayas-1?
Yeah, I chuckle a little bit, Derek, because we hope to get as many questions about mevrometostat at this point as we do about our own program.
Yeah, rinzimetastat, and at this point, I feel like we can speak in a pretty educated fashion about Pfizer's program. I think what folks caught was in Pfizer's Q2 quarterly call, they mentioned some further specificity around mevrometostat timelines, and so they narrowed the guidance to Q4 this year for the first readout of their first phase III study, MEVPRO-1. That obviously has, I think, positive implications if you do the trial modeling and event accrual modeling that the street is doing, and obviously that we've done. Under a whole variety of assumptions, you can make around control arm performance, control arm distribution, meaning distribution of patients to various aspects of the control arm, and how each of those components of the control arm might perform.
Really in any sort of reasonable scenarios you can construct, including assumptions you make around enrollment curve and exactly when Pfizer was fully enrolled and whatnot, them narrowing that guidance to Q4 seems to have positive implications in terms of how that study is likely to read out. I think more broadly, as you folks just take a big step back and look at the mechanism of action, look at the data that Pfizer has produced now in not just one population, but actually two different populations within castration-resistant prostate cancer from two different phase I data sets, and then subsequent to that, a randomized data set in the post-abiraterone CRPC population, which is the one that we are all talking about. You look at our own data with rinzimetastat, obviously in uncontrolled setting, but phase I data across those two different populations.
You now have about half a dozen different data points, all of which point to the synergy of adding a PRC2 inhibitor, which is what these drugs are, in combination with an AR inhibitor. All of that should play out quite favorably in addition to now the stats and trial modeling folks are doing around MEVPRO-1.
Excellent. I guess when you think about the trial, what would constitute clinically relevant data? I think we had done some work around stats, and I felt pretty good about it hitting statistical significance. But is that enough, or are we looking for a specific hazard ratio that, again, would be more clinically relevant?
Yeah, look, I think in terms of actual trial expectations, it is probably a question that is better suited to Pfizer as opposed to us. I think from our own perspective as drug hunters, drug developers, you obviously want to see as clinically beneficial a profile as possible on behalf of patients. You have a pretty good sense of what the control arm would do in this patient population. Maybe if you take a step back, Derek, from just the stats of the phase III trial alone and just think about the actual patient experience and what physicians in this space are looking for. Really what you are looking for is you have three big androgen receptor inhibitors that get used widely today. So that is enzalutamide, apalutamide, and darolutamide. In combination with those three drugs, you also have a fourth drug called abiraterone.
Those four are the ARPIs, and the ARPIs are the mainstay of therapy today for prostate cancer patients. The issue is, as good as those ARPIs do for patients, and with abiraterone in particular, which is the drug that we're talking about following at this point. What happens is once patients in the CRPC setting progress on abiraterone, there really are no other good options to give them. You can do an AR switch. You tend to get anywhere from four to six months of additional PFS when you do that AR switch. It's a tried-and-true treatment methodology for physicians, and what I mean by that is it's another oral agent. They're generally well-tolerated. Physicians are very used to giving those AR inhibitors. Obviously, the downside to that, though, is four to six months of PFS.
Really the holy grail in that space has been what do you give a patient that's progressed on abiraterone if you're trying to get more than that four to six months of PFS? While in the trial design, you obviously include chemotherapy as one of the options, nobody wants to give their patients chemotherapy in that setting. In terms of what would be clinically meaningful, if they can get anywhere from two to three months of additional PFS above and beyond what you can get with your other standard of care, in particular an AR switch, any of that would be clinically meaningful. Obviously, they're going to have to show a bit more than that in the phase III trial because they're also going to have to show that they can also do better than chemotherapy.
But really, if they get any control arm performance in the six to seven-month range, which is what folks seem to be quoting, their own trial is powered for 6.75 months of PFS in the control arm. Anything approaching a double-digit PFS would be game changing for those patients.
Got it. I guess, what do you expect from a safety perspective from that trial? I guess, how does that read through to you in terms of what you offer with rinzi?
Yeah. I think one of the key aspects of the differentiation here for rinzimetastat is thus far has been and is very likely to continue to be is the safety differentiation. And where that comes down to is this is good old-fashioned drug development 101 as you think about the pharmacokinetic properties of these drugs. In the case of mevrometostat, which is Pfizer's drug, it looks to have about a four- to five-hour half-life. In the case of rinzimetastat, ORIC's drug, we have a 20-hour clinical half-life. And what that extremely long clinical half-life gives us the benefit of, in addition to the fact that we're combining with darolutamide, one of the three big AR inhibitors, whereas they are combining their drug, obviously, with their AR inhibitor, enzalutamide. Enzalutamide is a CYP inducer. And so, what that means is that it's a well-known, well-documented CYP inducer.
It pushes down the exposure of drugs that are metabolized by CYP, which is most other drugs. And so, because of that DDI that they have with enzalutamide and their relatively short half-life of mevrometostat, they're having to give very large doses of the drug. And so, in their randomized data that they presented and in the phase III study, in either case, they're giving grams of drug in order to overcome those two shortcomings, the short half-life as well as the DDI with enzalutamide. In the case of rinzimetastat, our go-forward phase III dose is 400 mg once daily in combination with darolutamide. The reason we can go with such a low dose is because, one, we have that 20-hour clinical half-life, but also secondly, darolutamide is not a CYP inducer, so we don't have a DDI to overcome.
Where that really shakes out is in the PK of the two drugs, and you can imagine the PK curve for the combination of mevrometostat and enzalutamide shows you with two very large peaks during the course of a 24-hour period, and that's where you get Cmax-driven toxicity. Pfizer themselves have said that they believe it's Cmax-driven toxicity that they see. And so, you see on-target tox that you would expect to see. It's just at relatively high levels. So, you see both GI tox and Heme tox. In the case of the rinzimetastat combination, we also see that on-target tox. Of course, you should see on-target tox, but we see less of it and less severity of it, and that's because of that much better-behaved PK profile of the drug. That safety differentiation is key, and this is a space that has been well-conditioned to that.
As you look at the three big AR inhibitors, Pfizer's drug, enzalutamide, that they acquired from Medivation, that was the first AR inhibitor to market. Six years later came apalutamide from Johnson & Johnson, and its main differentiation was a slightly safer, better-tolerated profile, not a better efficacy profile. The same efficacy profile, but better safety. Darolutamide, Bayer's drug, which is now a $3 billion to $3.5 billion a year drug growing 60-plus percent a year, that phenomenal growth is not because of differentiated efficacy. It has the same efficacy as the other two AR inhibitors, but it has even better safety and better tolerability. My point being, this is a space that is very accustomed to accruing more and more share to new kids on the block that just have a better safety profile.
Got you. I guess we want to talk about some of the differences and kind of the learnings from mevrometostat. You guys are targeting EED rather than EZH2. I guess, what do you believe could eventually be some of the advantages down the road taking that approach?
Yeah. First of all, just from a terminology perspective, because we sometimes kind of pause or catch ourselves halfway through a conversation with an investor and just have to level set on the different targets we are talking about. The complex is called PRC2, and the PRC2 complex has three different subunits that can be drugged. Essentially, two are the ones that folks have focused on, which is either EZH2 or EED. In the case of mevrometostat, it is an EZH2 selective inhibitor. In the case of rinzimetastat, our drug, it is an EED inhibitor. What that means is that Pfizer is going about its inhibition of PRC2 through the enzymatic complex, so EZH2. And in the case of rinzimetastat, we are going at it from allosteric inhibition through the EED subunit.
Now, it really does not matter which subunit you drug in terms of initial ability to inhibit the PRC2 complex. And so in the case of mevrometostat, in the case of rinzimetastat, they have similar potency. What really is the difference is obviously a very different half-life, as I talked about earlier. Now, where it comes to play, though, is in terms of long-term resistance, and this is probably what you are alluding to, which is that there have been numerous, at least preclinical studies that have been done to elucidate the biology and would suggest that selective EZH2 inhibitors are susceptible to acquired resistance or bypass resistance from EZH1. So compensatory resistance from EZH1 or acquired resistant mutations in EZH2. And those are two things that an EED inhibitor would not be susceptible to, obviously, or for that matter, a dual EZH1/EZH2 inhibitor. So right now, that is theoretical.
Yeah.
It is preclinical. We will actually have a poster at ESMO where we dive into a bit more of that preclinical biology to kind of peel that back and show those resistance mutations popping up in response to EZH2 inhibitors. The reason why thus far clinically we just do not know is there just has not been a long enough experience for either us or Pfizer to elucidate that, but that advantage ought to go to an EED inhibitor.
Got you. Basically, we will have to wait for pretty long-term data to really see if there's any potential differentiation on efficacy and resistance mechanisms.
At least in terms of clinically, yes.
Yeah. Safety, though, we can get that fairly soon. We already know.
Safety, you already got it.
We already got it.
You got it.
Excellent. Maybe on that vein of safety, PRC2's been in the news with Taz kind of being pulled and also Fulcrum's drug. But maybe just talk about kind of the perception of the class in terms of safety, particularly given what's going on there, but even in light of maybe your and Pfizer's moves with even starting trials and basically engaging with the FDA within the class.
Yeah. There was a little bit of a brouhaha in the first half of the year, which was really around this risk of secondary malignancy that folks had observed with tazemetostat, and I think what we thought of as old news because the tazemetostat label was around for years, and folks should have been very well aware that in the tazemetostat label was a low risk, but a risk nonetheless of secondary malignancy. It was at the rate of 1.7% rate of secondary malignancies was what was quoted in their label. And you have to keep in mind that that was the preclinical or the non-clinical toxicology studies that you do in these spaces are intentionally designed to be very sensitive to pick up these kinds of signals . And in tazemetostat's preclinical work, there had been a very strong signal of secondary malignancy risk.
That was on the order of about half the rodents passing away from secondary malignancies or showing evidence of secondary malignancies. Despite that extremely strong signal preclinically, what it translated to was a 1.7% rate in the actual clinic and what made its way into the label. In the oncology space, for folks that have been in the oncology space for a while, you do not tend to get scared away by a low risk of secondary malignancy, and the reason is because there are lots of oncology therapeutics that have a low risk of secondary malignancy. In fact, when you look at the prostate space specifically, the drugs that really today make up a lot of the therapeutic interventions in prostate, so that would include chemotherapy, radiation, Pluvicto, enzalutamide for that matter, they all show low risks of secondary malignancy.
That is why a low risk of secondary malignancy is not in and of itself something that would dissuade development of a drug in the space. In the case of Fulcrum, they obviously could not come to agreement with the FDA on what a phase III study would look like. But what folks have to remind themselves is that that was in a completely different division of FDA, completely different indication, not an oncology indication. They were developing their drug for sickle cell disease, where you are anticipating dosing younger patients, adolescents for decades on a therapy. It is just a very different risk-benefit profile than what you see in the oncology space, certainly in the prostate space.
I believe through the public comments that Pfizer made, through our own public comments, it became clear that certainly I can speak for ORIC, we had not seen evidence of secondary malignancy in our preclinical studies. Remember I told you those models are extremely sensitive, and yet we saw no evidence of secondary malignancy or malignancy, I should say, in those preclinical studies. We have not seen that evidence in the clinic of secondary malignancy. I believe Pfizer has made some statements along those lines as well. As you alluded to, I think folks should also take comfort with the fact that obviously we and Pfizer have had extensive dialogue with the FDA as we have been prepping for phase III studies that are now, theirs is underway and ours is underway, and both companies are continuing with their studies.
They have also started a trial, right, in earlier line where the control arm could be 24 months or something like that, right?
Even longer than that.
Right.
Yeah, exactly. You are right to bring up. MEVPRO-2 is maybe the study you were alluding to where the control arm would do a couple of years, but MEVPRO-3 even more importantly, which is in the CSPC setting, the castration sensitive setting, is one where you would expect the control arm to do four plus years.
Yeah.
Again, that study is still ongoing, and Pfizer has not made any indication that they have been asked to change the design of that study or to stop.
Got you. I guess, focusing on rinzimetastat, what should we be kind of expecting
Sorry, Derek, just to interject by the way, because sometimes we do get the question from people saying, "Well, is it a risk that you may one day see a secondary malignancy with the program?" This is where I ask folks to maybe take a step back and see the forest for the trees, which is that in no way can we guarantee that we are never going to see a secondary malignancy with rinzimetastat, nor can Pfizer make that guarantee for mevrometostat. But the point, I just rattled off all the widely prescribed drugs in the prostate space that see rates up to the high single-digit percentages of secondary malignancy, and they're widely used in the prostate cancer space. The point is not that you need to come through this with no evidence whatsoever of ever seeing a secondary malignancy.
At low rates, it is still a very positive risk-benefit profile in terms of what you're offering to these patients to treat what is guaranteed to be a fatal cancer. That's where I think that folks need to focus on.
Got it. No, very helpful. So yeah, maybe in terms of your updates for rinzi, maybe talk to us, when should we get the next updates? Also, just for the Himalayas-1 trial, kind of timing that you guys have communicated to the street, and if you guys will give any updates along the way on enrollment.
Yeah. As you know, we give our guidance in January at a competitor conference, and we gave the guidance, and we intentionally called it a program update. The reason for that is we didn't specifically say it was a data update. So, what this second-half program update could include for rinzimetastat could be an update on the Himalayas-1 study, which as you guys know, we just started. Could be our thoughts on a potential second phase III study in prostate cancer, or it could be some additional data in either of the two patient populations. So that's a little bit of TBD.
Okay.
We'll see on that. With regards to the timing on the Himalayas-1, as you guys know, we said we'd start that study. We've started that study. That's ongoing. We're assuming about a 16-month enrollment period for that study, and we'd expect top-line data for that study in the first half of 2028. The primary endpoint for that study is PFS, so similar to the MEVPRO-1 study as well.
Got it. Perfect. I guess you brought up a little bit there, but how should we be thinking about rinzimetastat's expansion to other places in prostate? I guess right now you're in the post-abiraterone, Abi setting. Where else could you go, and is it going to be following the Pfizer playbook, or would it be something else? If you can elaborate on that.
All excellent questions, all under active discussion internally at ORIC. We're thinking actively about what Himalayas-2 and eventually Himalayas-3 will look like. There's obviously a lot to do within the prostate space itself. As part of our first half update, the data update we provided not only a data update on the post-abiraterone CRPC population, but also a second population within CRPC, which was post-AR inhibitor. So, patients who had progressed on either enzalutamide, apalutamide, or darolutamide, who we were then giving darolutamide as a re-challenge, essentially. It's an AR inhibitor re-challenge, which as you know is not a thing. AR inhibitor after AR inhibitor doesn't work. You should really be getting two months of PFS for everyone, because at the very first scan you're seeing progressions. That was not the case for us.
We saw at least as good early landmark PFS out of that population as we did in the post-abiraterone population, and that was something that gave us a great deal of confidence in not only the mechanism, but also what a second study might look like. So, Himalayas-2 could be in that CRPC setting post-AR inhibitor. But another population that's really captured our attention is obviously CSPC, castration sensitive prostate cancer. Any therapy that has been studied in the CRPC setting when it's then investigationally been successful in the CRPC setting when you take it into CSPC, works just as well, if not better. That would obviously be of high interest to us as well. So that would be something more akin to MEVPRO-3, what Pfizer's third phase III study is.
Those are both of high interest to us and right now we're just letting the data mature. We like what we're continuing to see out of our own phase I data. Keep in mind, we get to see the ongoing follow-up of our phase I data in CRPC in the two different populations. We like how those data are continuing to develop, and we'll continue to monitor that and make some decisions about one or more phase III studies to start next year.
Got it. Anything else on rinzimetastat or mevrometostat or just the CRPC space that you would flag in terms of what we should be watching for the second half of the year and maybe early part of next year?
Yeah. We'll have our own data that's developing in that space. The other thing that we're working on internally is obviously, we get asked by pharma parties that have their own favorite new mechanisms in prostate cancer, what this PRC2 mechanism does to expression of things like KLK2, for example, or PSMA or STEAP1, and all very interesting targets in the prostate cancer space, and all of which have their expression increased through PRC2 inhibition. We're continuing to do some more preclinical work in those areas, but certainly we're also thinking about other early clinical work that we might start in some of those areas, to see where else beyond AR inhibitor combinations might we develop rinzimetastat within the prostate cancer space.
We've also shown preclinically quite a bit of evidence around combining PRC2 inhibitors with other targets in other therapeutic areas beyond prostate, including breast cancer, colorectal cancer, lung cancer. Some of those are combinations with KRAS inhibitors. We have a lot on our plate, Derek.
Yeah
in terms of running down some of these opportunities, prioritizing some of these opportunities, and just figuring out what is going to be the most efficient and yet comprehensive development plan that we can undertake for rinzimetastat to execute this opportunity as quickly as we can.
Excellent. Well, maybe shifting gears to eno. Maybe just give a little background on that program and where you guys are in development there.
Yeah. So enozertinib is our brain penetrant compound for two different populations, within what are broadly called the atypical EGFR mutation. So, one of those populations is EGFR exon 20, and then the other population is more specifically PACC mutations or atypical mutations. The terminology gets used by different people in different ways, but those are the two broad populations within EGFR that we're looking at. Those are populations that folks know well because there's a lot of competitors that have tried and failed in those populations. There's a lot of ongoing competitors in those populations. The main issue has been, Derek, really some combination of either safety liabilities, either on-target safety liabilities, or in many cases off-target liabilities. And then the big issue has been a lack of CNS activity.
The reason why that matters so much for these targeted therapy populations is, look, some of us on the ORIC team, myself included, came over from a company called Ignyta about a decade ago, was working on targeted therapies in the lung cancer space. And I used to remember back then there was an active debate about whether you wanted a therapy to be brain penetrant or not. Because on the one hand, brain penetrance was quite important because so many of these patients, about 35%-40% of patients in the frontline setting present with brain metastases. The brain is often the first site of progression. And it ends up being what pulls in the PFS of these compounds is because especially the huge portion of patients that have brain metastases initially just do much worse on drugs that are not brain penetrant.
The flip side of the debate was people worrying about, well, are you going to get some kind of toxicity related to getting the drug in the brain? As it turns out, now it is dogma in that thoracic oncology space that you want a drug to be brain penetrant because physicians realize what an issue these CNS metastases are. What was a head scratcher for us, no pun intended, was that in this space, as you looked at the other drugs in development, the other drugs were not CNS active, not CNS penetrant. It was a real shortcoming of the space in both of these populations. That is really where enozertinib has tried to make its name for itself is really with that profound CNS activity.
Got you. Can you maybe just talk through the development strategy for eno and where you guys have been focused?
Yeah. We are pursuing it in two different patient populations, EGFR exon 20 and the atypical. We had a pretty extensive update in the second half of last year at ESMO Asia. Then, as you probably know, we have a poster at ESMO this year focused on the atypicals. When we look at that space in particular, we talk about what the benchmarks are there. If you look at the competitors out there, I think from a systemic response rate, it focuses on the low to mid 60% systemic response. What is interesting though, when you look at these competitors, the CNS response rate really drops off pretty considerably, and you see some of them at 30%, and some of them are not reported as well.
We think for a good, active CNS active drug, there should not be that big of a gap between the systemic response as well as the CNS response. Hopefully when we have our data update later this year, we can show hopefully we are better on one of those benchmarks and hopefully as good as on some of the others. The other thing we are seeing with some of these other competitors is a lot of off-target toxicities. This could be in the form of QTc prolongation, anemia, or elevated liver enzymes as well. We will have that. With exon 20, again, we are studying it in three different approaches there. That is EGFR exon 20. It will do monotherapy, then we are doing in combination with chemo, and we are doing it in combination with amivantamab as well.
Got you. I guess when we get all this data, I guess what's the next steps that you want to take? Obviously, with rinzi, you're moving into registrational trials. With eno, is there an independent path to bring to market, or do you want to partner this asset? Where do you think is the best way to, or what's the best path to creating value?
Yeah. It's interesting. When we talk about rinzimetastat and the path forward versus enozertinib and the path forward, I would say that there's a different lens that we look at the two of them through, Derek. What I mean by that is in the case of rinzimetastat, because it's in massive indications in prostate cancer, any one of the indications we've just rattled off is a multibillion-dollar market in the U.S. alone. For that reason, we've never tried to be heroes in the way that we've set our aspirations for rinzi, and what I mean by that is while there's many reasons, we think that our profile is going to end up being better than Pfizer's profile, and certainly on the safety side alone, we don't have to be better. We can be just as good as them.
In such large markets, even if you are a second to market with a relatively undifferentiated profile versus the first mover, you can still accrue such a large portion of the market that it's still incredibly commercially attractive. It's a different litmus test we would use in the case of the lung cancer program. What I mean by that is those are relatively smaller markets, and for that reason, you really need to be best. It can't just be tied. Along the criteria that Dominic mentioned, what we're going to want to see out of our own data and what we'll want to prove to others from the data is that he gave you three criteria.
He talked about the off-target toxicities of the other drugs, he talked about the systemic response rate of the other drugs, and he talked about the lack of CNS activity of the other drugs. We will need to be better than the other drugs on at least one of those criteria and at least as good on the other criteria to satisfy ourselves and others that the drug is better than others, not just tied for first place. Assuming that we can prove that we will then elucidate what the phase III strategy is going to be. But like I said, we have aspirations for that first phase III study to start next year for enozertinib.
Got you. As you think about the overall, again, smaller and different type of opportunity relative to rinzimetastat, what do you think that opportunity is for enozertinib?
Yeah. It is relatively smaller, but it is definitely not small. If you look at the EGFR exon 20 in the U.S. alone, it is about 2% of non-small cell lung cancer, so call it 4,000 or so patients in the U.S. alone. EGFR atypical is actually slightly bigger than that. It is about 2.5%, 3% of non-small cell lung cancers, so call it 6,000 patients.
The EGFR exon 20 by itself, we think in the U.S., it is about a $1.5 billion total addressable market, and we think the EGFR atypical is probably $2.5 billion addressable market in the U.S. alone. We do not think these are small. If you look at targeted therapies and you have a drug that is truly best in class, that is differentiated, that should gather the majority of the share. We think this is a sizable opportunity, and I think people are under-calling it.
Hopefully with data from competitors and our own data in the second half of this year, people will start giving us a little bit of credit for it.
Yeah. Then maybe just last question in terms of the cash runway. You guys can talk about being well funded. I think you have funded most of these trials, but maybe just walk us through again what is funded, what would need additional funding, and ultimately some of the levers that you would pull to do that.
Yeah. So, we ended the second quarter with $388 million in cash. That gives us cash runway into the second half of 2028. That does include the Himalayas-1 study and does include a phase III study for enozertinib as well.
Yeah.
This is a fully burdened number. The important thing is that cash runway takes us into the second half of 2028, which is past the top-line data readout from the first phase III study for rinzimetastat, which is the Himalayas-1 study. So, we're in a good position from a cash perspective. Obviously, we're a biotech. At certain points, we'll have to raise more money. But we feel pretty good on the position we're in today.
Excellent. So maybe to wrap, just lay out the next 12 to 18 months in terms of catalysts that we should be watching for that really impact you guys.
Yeah. We're obviously going to have a lot of data, a substantial amount of data from our own two programs now with rinzimetastat and enozertinib. I think that one of the underappreciated aspects of the story, Derek, is just how efficiently you can do the CRPC study. So, with a sole primary endpoint of radiographic PFS, you don't have a co-primary of overall survival. Obviously, our FDA will want to see a trend in overall survival, but that's not a co-primary endpoint. What it means is you can get your answer pretty darn fast.
For a study that we initiated just a month or two ago, when we are saying you are going to have a first-half 2028 phase III readout, it is funny when we think about it was not that long ago that we were talking to investors about ORIC having two different assets in phase I. Because of how fast things go in oncology, and particular how efficient the development is in the CRPC space, by the second half of 2028, you are going to have our first phase III readout. That is for an indication post abiraterone CRPC that, as Dominic alluded to earlier, is a $3.5 billion a year indication in the U.S. alone. 600-patient trial, you can just do the math on how much that costs. It is actually pretty efficient to do a trial both in terms of speed and cost in the CRPC setting.
Like I said, Himalayas-2 could be a post AR inhibitor CRPC study. Again, roughly the same size, same timeline, same kind of cash needs for a study like that as you do in the post abiraterone CRPC setting. That itself is a very large indication, just as large as that post abiraterone indication. You are going to get a lot of data from us over the next, call it 18 to 24 months, including the first phase III for rinzimetastat. Then, like I said, a substantial amount of data on enozertinib that will show whether that is also going to be a phase III program. While I hesitate to speak for others, I think you are obviously going to get a lot of data from our competitor, Pfizer, with mevrometostat. In Q4 this year, we are going to get their MEVPRO-1 readout.
They have said that MEVPRO-2, as of their August earnings call, they said MEVPRO-2 phase III readout was coming in the next 12 months. There is a lot that is happening in both of these spaces.
I guess maybe one more question. With the Pfizer data, they might provide just very high-level information. I guess if they were to provide the more detailed data at a medical meeting following that, should we be thinking about ASCO GU? Or when do you think, we would actually get to see all the goods of the MEVPRO-1 trial?
Yeah. I have no idea. That's a question that's much, much better suited to them. We're more focused on our own timelines right now.
Yeah.
There's obviously ASCO GU, there's ASCO next year, but who knows when they would present those detailed data.
Got it. We'll be on the lookout. Gentlemen, thank you so much.
As will we. Thank you.
Thanks. Yep. Thanks, Dominic. Good to see you.