All right, let's go ahead and get started. Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Rathi Pinhei, Priyanka Grover, and Joyce Zhou. Our next presenting company is ORIC, and presenting on behalf of the company, we have CEO Jacob Chacko.
Thank you, Anupam. It's my pleasure to speak to you today about ORIC Pharmaceuticals and the important work that we are doing within the oncology space. As always, I'll be making some forward-looking statements and encourage you to look at our SEC disclosures. So starting on slide three, ORIC stands for Overcoming Resistance in Cancer, which in a nutshell is the mission of the company. We've assembled a talented group of drug hunters and drug developers that have worked together for many years at prior leading oncology companies and have developed many successful and commercialized products to come together to work on a pipeline of exciting therapies for patients. So we have two late-stage pipeline assets, one focused on prostate cancer. That drug is called rinzimetostat, and a second program called enozertinib, which is for lung cancer.
Both of those drugs have presented, we've presented a substantial amount of data on both of those drugs in the prior years, especially 2025. We look forward to presenting a lot more data this year, as you can see in the upcoming anticipated milestones. The company is incredibly well-funded such that we've got cash runway into the second half of 2028. The importance of that runway is not really the second half 2028 part, but the fact that you're going to get your first phase III data readout for rinzimetostat, our prostate program, in the second half of 2027, and so we are well-funded for that first phase III program, and we are also funded for our lung program, which is also going into phase III studies, so I mentioned the management team. We've been together for years. We've been together at ORIC.
I've had the privilege of working with most of this team for seven years at this point. I recruited this entire team into ORIC. We've had the privilege of working together previously and knowing each other for many, many years, even prior to ORIC, and that makes all the difference in small biotech in terms of the ability to weather the storms of biotech, as we're all aware of. Slide five highlights the pipeline that we're working on. So I mentioned there are two late-stage development programs: rinzimetostat, which is a PRC2 inhibitor. Both of these are small molecule oral inhibitors. Rinzimetostat, formerly known as ORIC-944, is a PRC2 inhibitor which is being developed in prostate cancer in combination with two of the biggest drugs in prostate cancer today: apalutamide from J&J and darolutamide from Bayer.
Enozertinib, which was formerly known as ORIC-114, is a selective and, importantly, brain-penetrant TKI that is going after two different targeted therapy populations within non-small cell lung cancer: EGFR exon 20 and a group of mutations known as the atypical mutations, but more specifically PACC mutations. Now, within lung cancer, we're obviously testing enozertinib in combinations with chemotherapy and also with subcutaneous amivantamab, which is an approved therapy from Johnson & Johnson for this indication, and we're also obviously testing monotherapy. The important piece here, as you can see, and you can even see it from the clinical collaborations, is the strategic importance of these populations and of these targets, namely that these are high unmet need patient populations where there exists a dramatic area for improvement in both of these populations, and you can see that the commercial relevance of these populations is pretty much self-evident.
As you look at prostate cancer, even our initial indications within prostate cancer, which are focused within the castration-resistant setting and eventually the castration-sensitive setting, you can see our blockbuster opportunities many times over, and within lung cancer, these targeted therapy populations, while relatively small and smaller than the prostate cancer populations, are again individually blockbuster opportunities. Now, on slide seven, you can see what summarizes a very busy and transformative 2025, so starting with rinzimetostat. Rinzimetostat, again, is our PRC2 inhibitor being developed in prostate cancer. We reported a substantial amount of data last year that confirmed the potential best-in-class data and profile within metastatic CRPC. Now, as many of you know, we have one main competitor. It's a small company called Pfizer, which is working on the same mechanism, and they have demonstrated quite a bit of de-risking data of this mechanism of action.
In other words, a PRC2 inhibitor in combination with an AR inhibitor. Pfizer is studying their drug in combination, their PRC2 inhibitor in combination with their AR inhibitor, enzalutamide. We are studying our PRC2 inhibitor, rinzimetostat, in combination with the other two big AR inhibitors, apalutamide and darolutamide. Now, in all of these cases, we've been able to show, in combination with APA and in combination with Daro confirmed PSA response rates that compare quite favorably to Pfizer's response rates. We've shown really profound ctDNA clearance, and I'll give you some snippets of those data later in the presentation, and most importantly, we've shown a clearly differentiated safety profile. The name of the game here in this space and with this target is going to be the safety profile.
And we're very encouraged by the fact that even with the early dose exploration data that we presented last year, we already see definitive evidence that that safety profile is emerging. In other words, the benefit of our drug and its long half-life and its strong drug properties is emerging in the form of a strong differentiated safety profile. That's important because it's going to be compatible with long-term dosing. And as I said, the name of the game here in prostate cancer, certainly in CRPC, but especially as you go earlier line into CSPC, castration-sensitive prostate cancer, is going to be to have that clean, well-tolerated profile. Importantly, last year, we selected the provisional recommended phase II doses of our drug, rinzimetostat, in combination with both apalutamide and with darolutamide.
We presented a substantial amount of data related to that, which I will give you some highlights of later today. And importantly, we initiated dose optimization in combination with both of those drugs, and we look forward to presenting some of those dose optimization data later this year. We were also busy, equally busy, on the other program, enozertinib. So within lung cancer, we presented a substantial amount of data actually just two months ago at ESMO Asia in two different oral presentations of our drug, enozertinib, as a monotherapy in EGFR exon 20 and separately in EGFR PACC mutations, both within non-small cell lung cancer. I mentioned to you earlier that brain penetrance is the key differentiator for this program.
Importantly, while we're thrilled that we showed systemic ORRs that are as good or better than the competition in the space, the most important thing for us to show in that data update was the intracranial activity of the drug, and that's because of the high prevalence of CNS metastases within this population. In the dataset that we presented, we saw a 100% rate intracranial ORRs in patients with measurable disease. That is an incredibly high number, and it's one that is not often seen in this space, even across other targets within targeted therapy, non-small cell lung cancer. We're quite proud of that, and it continues to help differentiate the program relative to what is otherwise a fairly competitive landscape. We also had a well-tolerated safety profile, and importantly, we selected our phase III dose at that time. On the corporate side, we were equally busy.
We raised a lot of cash, as you can see from the slide, and importantly, the importance of that cash was extending the cash runway into the second half of 2028, which, like I said, is well beyond the phase III data readout for rinzimetostat, which we expect to occur in the second half of 2027. So with that, let's dive into the programs. So rinzimetostat, as I mentioned, formerly known as ORIC-944, is a PRC2 inhibitor. For folks that have followed the prostate space, you know that PRC2 inhibitors have been studied by multiple companies with multiple drugs previously. The issue has been what you see here. This is what I like to call the problem statement.
So the key limitations at the top of slide nine show you what has really plagued the field and the clinical experiments with PRC2 inhibitors previously, which is namely the running the gamut of things that you don't want to see in optimal drug profiles. So in other words, poor in vitro potency, poor in vivo potency, as if that wasn't bad enough, inadequate clinical drug exposures related to things like CYP autoinduction and, importantly, short half-lives. And then all of those drugs have also been plagued with suboptimal tolerability, which really comes back to the poor PK properties and the poor drug properties. Now, I mentioned the competitor compound from Pfizer, mevrometostat, seems to have solved some of these issues, though not all of the issues.
Importantly, by solving some of the issues, they have been able to show de-risking clinical data that really has helped validate the promise of the synergy of a PRC2 inhibitor in combination with an AR inhibitor in prostate cancer. With rinzimetostat, we think that we have similarly solved actually all of these challenges. In that, I mean that we are selectively targeting the PRC2 complex. We go at it through the EED subunit of PRC2. We have excellent in vitro and in vivo activity. We have synergistic activity with AR inhibitors that at this point we've showed both preclinically as well as in the clinic.
And most importantly, we have demonstrated many times over now the strong drug properties and the well-tolerated aspects of the drug, both as a single agent, but also in combination with both of the AR inhibitors that we are studying it in combo with. So I mentioned that we're conducting dose optimization right now. We're doing that in collaboration with J&J, with apalutamide, and separately with Bayer, with darolutamide. And we expect to report more of those dose optimization data later this year. The big, big thing that's happening in the background, the team's been running very hard at actually for the bulk of 2025 and obviously even now into early 2026, is standing up our first phase III study. So for rinzimetostat, we expect that we will initiate our first phase III study in the first half of this year. As I mentioned, these are quick studies.
There's a profound signal effect that is expected to be seen, and so we expect the primary data readout to come in second half 2027, not too far from now. Now, slide 10 is one slide that summarizes a lot of complicated biology. So I'm going to, I won't do it justice, but I will try to summarize for you essentially very complicated biology around the PRC2 complex. So PRC2 is an epigenetic modifier. As you think about the big AR inhibitors, the androgen receptor inhibitors in prostate cancer, they have done profoundly well in terms of treating patients. But eventually, those AR inhibitors or the broader class of what are known as ARPIs, including abiraterone, eventually those patients, as well as they respond to the ARPIs, eventually become resistant. And what happens is that the tumors mutate. They essentially become AR-independent.
And at that point, it doesn't matter if you are shutting down the AR signaling axis. And so the promise of a PRC2 inhibitor is that a PRC2 inhibitor is an epigenetic modifier. And through the modifications with a PRC2 inhibitor, you should be able to, the theory has been you should be able to push the tumor to stay in an AR-dependent state. And in other words, allow the AR inhibitors to do what they're supposed to do, which is shut down that AR signaling and really should lead to more durable benefit of those AR inhibitors. And as I mentioned, we have now seen that clinical evidence both in a single-arm setting as well as a randomized setting from our competitor compound that Pfizer is developing. Now, taking a big step back on slide 11, why does this matter?
Why are we talking about combining a PRC2 inhibitor with AR inhibitors? For folks that have followed the prostate space, you know that the AR inhibitors, the three big ones being Nubeqa, darolutamide from Bayer, Erleada, which is apalutamide from J&J, and then Xtandi, which is enzalutamide from Pfizer, those three inhibitors, as well as abiraterone, which is now generic, the broader class called ARPIs, have transformed the standard of care in prostate cancer. You will be hard-pressed to find a physician or a patient in prostate cancer that is not heard of or is treated by these drugs, and the commercial numbers obviously validate the statement I just made, which is that the three big AR inhibitors collectively sell $11 billion of revenue globally.
The issue has been, if you talk to the prostate cancer physicians or the patients, what you will hear is that these drugs eventually stop working. And when they stop working, there's not a good option for patients. Or what you'll hear is that the options that are there for patients are ones that the patients don't want to take. So in other words, things like chemotherapy or other modalities that are actually much more complicated to deliver, come with much more toxicity, are administered by a different physician altogether. And so the holy grail has been, can you come up with a drug that would make these AR inhibitors better?
And so the pitch is quite simple here, which is that if you have a small molecule oral inhibitor that is well tolerated, that you can add on to an AR inhibitor to extend the durability of that AR inhibitor, either after the patient has already progressed on another ARPI or even before they've ever progressed on an ARPI, that pitch is self-evident as to why that appeals so much to physicians and patients. Now, I mentioned to you that this PRC2 target has been studied in prostate cancer before, in fact, studied by multiple companies with multiple drugs, and the clinical data haven't generally panned out. Now, why is that?
So if you look at the first-gen compounds and you see a couple of them profiled here as representatives, but really all the first-gen compounds seem to have the same general properties as what's displayed here on slide 12, which is that you see that they really suffer from liabilities on a number of different fronts. So they've had poor potency, they've had poor in vivo activity. Importantly, several of them have had what's known as CYP autoinduction. What that means is that those drugs will rev up the CYP enzymes, and those drugs are also metabolized by the CYP enzymes so that in the case of some of those drugs, the more drug that was given to the patients, the lower exposure of the drug the patient actually saw biologically.
Clearly, that's not going to lead to a clinical experiment that's going to do justice to the mechanism of action. Now, mevrometostat, which is Pfizer's drug, seems to have solved a lot of these properties. They have a drug that is very potent, has good in vivo activity, has solved some of the drug property issues, does not look like it has CYP autoinduction, has a somewhat better half-life. So in contrast to the one- or two-hour half-life of the first-gen compounds, the Pfizer compound appears to have about a five-hour half-life or so. Obviously, that is still a profile with some room for improvement, but with that profile alone, they've been able to show some pretty profound activity in combination with their AR inhibitor, where they have more than doubled the progression-free survival that you would expect from an AR inhibitor alone.
With rinzimetostat, you see the representation on the right-hand side of slide 12, which shows that we've got excellent cellular potency and in vivo activity. Clinical half-life of 20 hours, which is compatible with once-a-day dosing, obviously leads to a well-behaved PK profile. The toxicity that you expect to see here would be Cmax-driven toxicity. So that's why it's so important to have a long half-life with a well-behaved PK profile. And it does seem to be validating in the clinic. Now, slide 13 is a schematic of the study as it exists today. The left-hand slide is what has been completed, which is dose exploration. As I mentioned to you, we did both single-agent dosing with rinzimetostat, but of course, dose exploration in combination with the two big AR inhibitors that I talked about, apalutamide, which is J&J's drug, and darolutamide, which is Bayer's drug.
Having done a significant amount of that dose exploration last year, we identified that the drug works. Rinzimetostat works equally well with both of those AR inhibitors. It works at least as well as Pfizer's combination has been able to show, and it's been able to do that with a safety profile that at this point looks better than what Pfizer has been able to show. And we've shown that at multiple different doses, so we selected doses for dose optimization, obviously for Project Optimist purposes, and the right-hand side of slide 13 is really what's going on right now, which is dose optimization in combination with both of those AR inhibitors. We're studying two different populations right now, so within the metastatic CRPC setting, we're looking at one population that is post-abiraterone.
So in other words, they've already progressed on abiraterone, and they are now receiving an AR inhibitor, either apalutamide or darolutamide in combination with our drug, rinzimetostat. We are also separately studying a second population of interest within metastatic CRPC that is actually equally large, which is a population that has previously had an AR inhibitor, so either ENZA, APA, or Daro, and is now being dosed with rinzimetostat in combination with either APA or Daro. So all of that dosing work is ongoing right now. And as I mentioned, we expect to report some data from that dose optimization in the first quarter of this year. Now, to quickly review on slide 14 and a few of the subsequent slides, just some of the key highlights from the dose exploration data that we presented last year. Slide 14 shows you a PSA waterfall plot.
So why do PSA responses matter? These are generally thought of as early proxies of long-term durability within prostate cancer. Obviously, the gold standard for an approvable endpoint remains radiographic PFS. We're not there yet. We're in the earlier stages. And so we look at PSA 50s and PSA 90s as one metric of the activity of the drug and another way to benchmark against, obviously, the competition. Now, first question you ought to ask when you look at a PSA waterfall plot like this of a combination regimen is, what would you expect from an AR inhibitor alone in this setting? So in other words, if patients, all these patients are in the metastatic CRPC setting, they've all progressed previously. 100% of them have progressed previously on abiraterone. Up to one prior line of chemotherapy was allowed in this population.
And in that setting, it is a very well-documented population that with an AR inhibitor alone, you would expect to see roughly a 15% rate of PSA 50s and roughly a 5% rate of PSA 90s. You obviously see a far higher rate here, a confirmed PSA 50 rate of 40% as opposed to the 15% I mentioned. And you see a confirmed PSA 90 rate of 20% as opposed to the 5% that I mentioned. So that is in line, actually higher than the numbers that you see from Pfizer and the randomized data that they presented. And importantly, you're seeing that regardless of the combo agent. So in other words, we see that same activity, whether it's apalutamide or darolutamide that we're combining with, we see that same activity at all the different doses that we tested.
And so obviously, we're taking a few of those doses forward for dose optimization. Now, slide 15, if you'll allow me to nerd out for a little bit, is ctDNA data. And the question you should ask here is, why does ctDNA data matter in light of what I just showed you on the PSA activity? And the reason is there's now literature that says that even more than the linkage between PSA responses, PSA activities to long-term durability measures like PFS, ctDNA actually tracks even better for a long-term durability, for a proxy of long-term durability within prostate cancer. And this is why all the recent prostate phase III studies have used ctDNA as an exploratory endpoint as well.
What you can see on the left-hand side of slide 15 is that we have a 59% rate of taking ctDNA in patients from detected to not detected. The right side of slide 15 helps you contextualize whether that 59% is good or not. So what I'll show you, the first two bars on the right-hand side of slide 15 are active standards of care that otherwise get used in this population. You can see that enzalutamide, these are phase III studies that looked at these agents. You can see enzalutamide achieved about a 12% rate of ctDNA going from detected to not detected. Whereas chemotherapy, which would be another active standard of care in this setting, has about a 32% rate of ctDNA going from detected to not detected.
In the case of rinzimetostat, we saw a 59% rate of going from detected to not detected, which also bodes well for the activity of this combination and the synergy of the combination. So slide 16 tries to summarize a lot of data from both ourselves and obviously the competitor. The first two columns on slide 16 are showing you a highly summarized version of the randomized data that Pfizer showed last year with mevrometostat, which, like I said, those data were profound, full stop. You saw greater than a two-times extension of the PFS that you would expect with enzalutamide alone. And that was in a controlled setting. The control arm performed exactly as you'd expect, which is a 6.2-month PFS. And their treatment arm got a 14.3-month PFS. Now, you can see the corresponding statistics to go with that.
So as you look at PSA 50s and PSA 90s, Pfizer more than doubled the PSA 50s and the PSA 90s that you would otherwise expect. But you can see it comes with a fair bit of toxicity. So as you look at the middle column, you can see a decent amount of toxicity. You would obviously expect to see two big classes of toxicity with the PRC2 inhibitor, which would be namely hematological toxicity as well as GI toxicity. And you see both of those things. You also see alopecia. You see obviously a high frequency of these things and also a high intensity.
Now, in the case of rinzimetostat plus the two AR inhibitors we looked at, you can see in the far right column. I won't go through every one of these AEs, but you can visually see it's quite evident that you see less toxicity, both a less frequency and less intensity of that toxicity. And that's going to be, at the end of the day, what wins the game here. I won't spend too much on slide 17 because I think you all know that the prostate market is large. And as good as the therapies have been thus far, there is need for better therapies. There's need to kind of improve the standards of care that exist today. And you can see with any one of these potential phase III studies for us, it's a multi-billion dollar opportunity just in the U.S. alone.
I don't have nearly enough time in this presentation to talk to you about the biological evidence for PRC2 inhibitors outside of prostate cancer, but really the right-hand side of slide 17 attempts to show you, to summarize for you, several areas that we would intend to eventually develop our PRC2 inhibitor as well, which is there's ample evidence, at least preclinically, that PRC2s have the same epigenetic, synergistic effect in combination with KRAS inhibitors in lung and in colorectal cancer, and importantly, in combination with estrogen receptor inhibitors in breast cancer, so these are areas that we also look forward to developing and proof of concept in the clinic in the time to come. So with the time remaining, I do want to make sure we talk about our lung program as well, so enozertinib, formerly known as ORIC-114, is a brain-penetrant inhibitor of EGFR.
Slide 19 shows you the problem statement here, which is that as you look at this space for those that follow the lung cancer space, you will instantly recognize that within targeted therapies for lung cancer, we have had a lot of good development of drugs for various targets within non-small cell lung cancer. But EGFR exon 20 and EGFR PACC mutations remain two classes or two slices of that non-small cell lung cancer pie that are still incredibly underserved today. So there is one approved agent for EGFR exon 20 that is amivantamab from J&J. That drug is obviously not brain-penetrant. There's a lot of agents in development for EGFR exon 20 and others that are in development for EGFR PACC. None have shown profound CNS activity, with the exception, I would argue, of enozertinib. The CNS activity matters because 50% of these patients will eventually develop brain metastases.
Where you see the impact of durability of these drugs that are not brain-penetrant is because the patients eventually progress in the brain. That is the flaw in the armor of all of these drugs that are not brain-penetrant. Previously, I and many of our team members worked at a company called Ignyta. We developed a targeted therapy for non-small cell lung cancer there. And we saw the benefit of having a brain-penetrant compound and what that leads to in terms of increased durability. And that's exactly what is missing from both of these spaces, EGFR exon 20 and EGFR PACC mutations. The other thing that has plagued the field historically with some of the first-gen compounds here were tolerability issues related to either GI tox or skin tox. A lot of that has been solved by us and by others in the field.
I think at this point, the remaining piece of the puzzle to solve is really the lack of CNS activity. Now, we presented a lot of data here just a couple of months ago. The summary of that data, I'll show you some of the highlights and the slides to come. The really high-level takeaway is that the data had response rates that were at least as good as competitors, if not better, in terms of systemic responses. Importantly, as I highlighted in my opening commentary, we had 100% intracranial ORR in patients with measurable disease. That is an incredibly high level of activity in terms of CNS activity. That was in the context of enrolling patients. In contrast to the competition in this space, we enroll patients with active untreated disease into the study. In other words, they're allowed into the study.
Almost all the other programs, certainly in their early stage, all of the programs excluded those patients. And in later stages, most of the programs still exclude those patients. And what I mean by that is they require that if a patient has CNS metastases, those metastases need to have been treated with surgery or radiation prior to coming on the study. That's obviously not a good way to detect whether your drug is CNS penetrant and able to treat CNS metastases. We allow patients with active untreated mets onto the study and, in fact, enrolled a substantial number of those patients and see that profound CNS activity in those patients as well. Now, we've selected 80 mg once daily as the go-forward phase III dose.
As I mentioned, we're prioritizing first-line development in EGFR exon 20 and in EGFR PACC mutations, in some cases as a monotherapy, in other cases as combinations. We expect a substantial amount of new data to be presented in the second half of 2026. Slide 20 is a stylistic depiction of why that CNS activity matters. The top half of slide 20 just shows you some of the facts that I mentioned before, which is that at initial presentation, approximately a third of patients have brain metastases at initial presentation. The important part, if you talk to a radiologist or you talk to a medical oncologist, what you're going to hear is that that's the third of patients that you know have brain metastases because you can see it on imaging.
There is another group that obviously we don't know the size of that group that have what are known as micro-metastases, meaning that the mets are there. You just can't pick them up on standard imaging these days. And so the number is certainly higher than 30% or 33% at initial presentation that have these CNS metastases. And then what happens is that eventually, as you go into later lines of treatment, up to half of these patients will present with CNS metastases. But the biggest issue is really what you see at the bottom half of slide 20, which is that for drugs that are not brain-penetrant, no matter how good they might be systemically, eventually patients will progress. And for non-brain-penetrant drugs, they will often progress in the brain. And so these CNS metastases will occur. That'll be the site of progression.
And at that point, the patient is really out of options. They have to go to something that's a lot more invasive in terms of treatment. Where this comes out in the data, so as you can, we're students of the targeted therapy lung space because, as I mentioned, some of us worked together previously at Ignyta. And what you can see time and time again, whether it's ALK, ROS, EGFR, any of the big targets in non-small cell lung cancer, is that for drugs that are not brain-penetrant versus drugs that are brain-penetrant, you will achieve generally the same systemic response rates. Where you tend to have a big difference is progression-free survival. For the drugs that are brain-penetrant, you end up getting longer progression-free survival. The bottom half of slide 20 essentially explains why that is.
As you look at these drugs, both of which were developed in EGFR exon 20, both of which are not brain-penetrant, you can see there's a profound difference in the PFS, the durability of these drugs in patients with versus without brain metastases, and so for a drug that is brain-penetrant, if you can close that gap, and in other words, have both populations perform more like the good bars, in other words, the patients without brain metastases, you'll essentially end up getting a longer progression-free survival, so slide 21 shows you what we've done and what we are doing right now, so like I mentioned, we're focused on EGFR exon 20, both monotherapy of enozertinib as well as combos with J&J's drug, which is subcutaneous amivantamab, as well as a combination with chemotherapy, and then separately, we're studying the drug in EGFR PACC mutations as a monotherapy.
Now, we presented a lot of data in two different oral presentations two months ago at ESMO Asia. Slide 22 is essentially a one-slide summary of the key snapshot of those data, and what you can see in the top half of slide 22 is that relative to competitor benchmarks in the pretreated population, the reason we're highlighting, even though we're not focused on pretreated for later line development, the reason to spend a second here is because these are the most well-studied data sets, both from ourselves and from the competition. You can see that enozertinib delivers a response rate that's at least as good as the competitor benchmarks, if not better.
Then importantly, on the bottom half of slide 22, as you can see, obviously, as you move to the front line, you see even better response rates and then the 100% intracranial ORR that I mentioned earlier. Slide 23 is just a little bit of a double-click on that activity that I mentioned to you. The waterfall plot speaks for itself in terms of the activity of the drug. So you see very good activity in front line EGFR exon 20 in this waterfall plot. And like I mentioned, the asterisks at the top of the waterfall plot are showing you the patients that have CNS metastases at initial presentation. You can see even a greater percentage of those patients had CNS metastases at initial presentation than the 33% that I quoted to you earlier. There is some sense of physicians and patients voting with their feet here.
In other words, we do tend to enroll a higher percentage of our patients that end up having CNS metastases at baseline because the physicians know that the drug is brain-penetrant, and you can see that regardless of whether the patient has mets at baseline or not, you see that good systemic activity, and importantly, slide 24 is, I'll call it the triple check of those patients with CNS mets at initial presentation, and you can see with all the complicated annotations on the slide, the point of that is that we enroll patients, several patients with measurable disease. We enroll several patients who had active, untreated disease before they came onto the study. It doesn't matter which of those categories they fall in. You see profound activity of the drug, including two complete responses.
And those complete responses, it's worth noting, are in patients with what are known as non-target lesions. The reason why that's important is in patients with what are called non-target lesions in the brain, the only way to get an official response, so to speak, is to completely clear all the lesions. So in other words, if a patient has five lesions and you clear four, that does not count as a response. The way the criteria work in patients with non-measurable lesions, you can see we completely clear the lesions in all those patients. And here's one example on slide 25. All the data, all the waterfalls, none of it, all of it pales in comparison, I would say, to the actual patient stories. And this is where I spend a lot of my time, is understanding the activity of these drugs and why it matters.
So this is a 60-year-old female who presented with frontline EGFR exon 20, had five lesions in her brain at initial presentation, had no prior surgery or radiation for those lesions. And you can see after one cycle, she had a partial response, 47% reduction systemically. And importantly, after one cycle, disappearance of all five CNS lesions. So that is profound CNS activity. You can see that the drug safety profile that she experienced, which was well tolerated, and a duration of therapy that at the time was six cycles and ongoing. Similarly, in the PACC population, you can see we have very good systemic activity here, as demonstrated by the waterfall on slide 26. And then similarly, as I showed you for EGFR exon 20, slide 27 is the double-click on the CNS, the patients with CNS lesions who have these PACC mutations.
Again, you see profound activity, including complete responses in this population, and that includes most of these patients actually having active, untreated disease before study enrollment. Again, here, the patient stories are what speak volumes more than any other slide of data that I can show you. Slide 28 shows you a patient, a 67-year-old male who came in with a PACC mutation, frontline PACC mutation, and had a systemic response of 43% after the first cycle. After the first cycle in the brain, he had a 66% reduction of his measurable lesions, but after cycle four, that had moved on to a deeper response, in fact, a complete response, and was at cycle five and ongoing. So we get a lot of questions from investors around the market opportunity for lung.
As some of you probably know, I think the investor enthusiasm waxes and wanes around targeted therapies over the course of time. It seems to be tied to what was the latest acquisition in the targeted therapy lung space. But you can see that these populations are sizable populations. They're populations that matter. These populations, any one of them, whether it's EGFR exon 20 or EGFR PACC, is larger than ROS, larger than RET. There's a substantial commercial opportunity here. More importantly, there's a substantial patient need here in these populations for drugs that are truly active, well tolerated, and brain-penetrant. And so with that, in summary, you can see here on slide 31, again, the active pipeline that we've got going in both prostate cancer and lung cancer. As I hope you've heard in my commentary today, we think that these drugs are substantially differentiated from the competition.
There's a lot of milestones to come, a lot of activity going on at the company. And importantly, we're about to embark on one, if not two, phase III studies for these programs within the year to come. So with that, I'll turn it over to Anupam for any questions.
Thank you, Jacob. We're coming up on time here. So I just first wanted to see if there's any questions in the audience. Yeah, go ahead.
Diffuse bilateral glioma, pediatric diffuse bilateral glioma is characterized by 85%. Bilateral pediatric glioma characterized by exon 20 EGFR mutants, main driver event. Do you have any plans to make your inhibitor available for compassionate use or investigator-initiated trials in that setting?
Yeah, we're aware of the data or the clinical rationale in that space. We have thus far not studied the drug in glioma.
That's not to say that we're closing the door on that. So we'd certainly be open to a conversation around that.
On the dose-optimized data that's expected in Q1, can you give us any sense of more granular timelines? This is going to be, I think, ASCO GU coming up. There's also your press release webcast scenario that we could consider. How should we think about that?
So the data will be coming sometime between today and March 31st is how I'd probably characterize it.
Yeah. Solid guidance. Thank you. Yeah. All right. Okay.
Within this quarter. Yes.
Next 75 days or so. Yeah. All right.
Maybe then you could talk to us a little bit about the size and scope of the data that we're going to be getting and what you would really focus us on, given what you already know and what Pfizer has shown.
Yeah. I'd be pleased to expand on that question. We expect to see about 20-25 patients' worth of data. What we've said is that obviously we're studying the drug in two different populations within metastatic CRPC. We're going to focus that Q1 disclosure on one of those populations of interest. Presumably, it will be the population that we intend to start that phase III study in in the first half this year. Then we intend to focus that disclosure on one of our AR inhibitor combo partners of interest.
Again, presumably, that's the one that we intend to take into the first phase III study. The 20-25 patients' worth of data, what we're going to present is, like you've seen from us before, obviously PSA 50s, PSA 90s, ctDNA data in terms of efficacy. We will have whatever is available in terms of durability because obviously that's a key question here. We'll be looking for signs of durability that we are tracking towards what mevrometostat was able to show. And certainly that we're hopefully tracking definitively better than an AR inhibitor alone in that space. Some type of landmark analysis on the durability side. And then most importantly, safety.
As I mentioned, we're going to want to see that the safety profile is clearly differentiated from that of the competitor combination because that is what's ultimately going to lead to the long-term radiographic PFS and win the day.
I noted that in your comments, you noted at least three times that your first pivotal trial would read out in the second half of 2027, which would put you how far behind Pfizer in terms of timelines?
Yeah. I mean, as exciting as I think our pipeline is, I think we probably get more questions about Pfizer and their timelines. So what they have said is that, in fact, Albert reiterated yesterday in his presentation that they're going to have their first phase III readout for MEVPRO-1 this year, 2026, and so I guess it depends if that readout happens tomorrow or December 31st.
But the point is, I think we're roughly, call it 18- 24 months behind them. We intend to run as hard as we possibly can to keep that gap or close that gap. But the race is on.
Thank you, Jacob.
Thank you.