Good afternoon, everyone. Welcome to the next session with ORIC. I'm Ami Fadia, Senior Biotech Analyst here at Needham. It's my pleasure to be hosting Dominic Piscitelli, the CFO, and Matt Panuwat, Chief Business Officer of the company. I'll let you all take us through the presentation, and we'll have some time at the end for Q&A. For our listeners, if you have any questions that you want to send over to me, please use the dashboard. With that, let me pass it on to Dominic.
Great. Thank you. Thank you for inviting us to the conference and the opportunity to present. Matt and I will both tag team the presentation. I'll start off, and then Matt will do the second half. Before we start, we will be making some forward-looking statements throughout the presentation. We will refer you to our SEC filings, which highlight the risks, uncertainties, and investing in ORIC stock. ORIC is a clinical stage oncology company. Our name really does encapsulate our overall mission, which is to overcome resistance in cancer. We have two lead programs that we'll talk about today. One is a potential best-in-class PRC2 inhibitor that we're studying in prostate cancer. The second is a potential best-in-class TKI that we're studying in three forms of lung cancer: EGFR exon 20, HER2 exon 20, and atypical.
Because of the team and the capabilities that we've established in-house, we do have a two-pronged approach to building out our pipeline, which is both internal research and development, as well as opportunistic external business development. We've got an experienced management team, which, again, we'll talk about a little bit later. From a cash position, we're in a relatively strong cash position. We've got $256 million as of the end of 2024. Based on our current operating plan, that gives us cash runway into 2027. The bottom half of the slide here, I won't go through each one of these, but you kind of see the number of milestones that we have across both programs, both in 2025 through mid-2026, which we can touch upon a little bit later as well.
Looking at the team that we've assembled, we really have all aspects of building a leading oncology company. Our discovery research team comes from the likes of Genentech, from a development, clinical, and regulatory, the likes of Aragon and Ignyta, and then from a strategy and licensing from the likes of both Medivation and Ignyta. Lastly, we just started building out our commercial team with experience from the likes of Genentech and Pharmacyclics. Now, because of the team that we've assembled and expertise of the team, our key areas of focus are small molecules, and the three areas are prostate cancer, lung cancer, and breast cancer. Slide five, here's a high-level snapshot of our overall P&L. ORIC-944, this is our allosteric PRC2 inhibitor that we're studying in prostate cancer.
As you can see here, we're studying in two different combinations: one in combination with apalutamide and another cohort in combination with darolutamide. Again, these are metastatic CRPC patients. As you can see here, we have a clinical trial supply agreement with Johnson & Johnson for apalutamide and with Bayer for darolutamide as well. The bottom half here, we have ORIC-114. This is our EGFR HER2 inhibitor. As you can see here, again, we're studying this in three different patient populations: EGFR exon 20, atypicals, and HER2. Here we're studying both in first-line settings, as you can see, as well as second-line and later settings as well. Matt was able to get us a second clinical trial supply agreement with Johnson & Johnson here for subcutaneous amivantamab. We are studying ORIC-114 in combination with amivantamab in the first-line EGFR exon 20 setting as well.
I'll start off with 944, and then I'll hand it over to Matt to go through 114. PRC2 inhibitors have been studied in prostate cancer going back 10 to 15 years, going back to GSK, Constellation, Epizyme, and others. The issue that has really plagued the first-generation PRC2 inhibitors has been really poor drug properties, which, again, we'll touch upon a little bit in the coming slides. With 944, we do think we have a potential best-in-class program. You look at the preclinical profile as well as the early clinical profile of the drug, and then we'll talk about where we are at the program and kind of next steps as we move this program forward. For those who are less familiar with PRC2 complex, it does have two druggable subunits, both EED and EZH2. Most people are familiar with EZH2.
This is the sub-unit that most of the first-generation PRC2 inhibitors have approached. There is an approved EZH2 inhibitor on the market. This is a drug from tazemetostat from Epizyme, which is now with Ipsen, which is approved for both epithelial sarcoma and follicular lymphoma. Now, everybody's been studying combinations with PRC2 inhibitors with AR inhibitors, again, for many, many years. The data has been underwhelming until recently. What I'm referring to is data that Pfizer put out starting in May of 2023, with additional updates through 2024 into early 2025, again, which we'll touch upon in the presentation today. Taking a step back here, no one has really shown any robust single-agent activity with PRC2 in prostate cancer. It is all about combinations. This cartoon, this illustration is trying to highlight a very complex biology.
Basically, when you look at the second-generation AR inhibitors like enzalutamide, apalutamide, and darolutamide, they obviously provide a great option for prostate cancer patients today. Over time, these patients do gain resistance to AR inhibitors. What basically happens is these cells transition from an AR-dependent state to more an AR-independent state. That is where the AR inhibitors kind of lose their efficacy. With epigenetic modifiers like PRC2 inhibitors, like both mevrometostat from Pfizer as well as ORIC-944, the underlying hypothesis here is you're pushing these cells back to a more luminal-like, a more hormone-dependent stage where they synergize with the AR inhibitors, and they basically have incremental benefit as well. Here we're trying to conceptualize what we just basically said about the first-generation PRC2 inhibitors. CPI-1205 and tazemetostat, these we're referring to as the first-generation EZH2 inhibitors.
As you can see here, both these programs had poor cellular potency in vitro, poor in vivo activity, and poor drug properties. For example, tazemetostat actually had a CYP autoinduction issue where they actually saw a decrease in exposure with repeat dosing of the drug. Obviously, not what you want with your program. They also have very short half-lives in the likes of two to three hours. Mevrometostat, which we're referring to as a second-gen here, this is a drug from Pfizer, which they've shown some really compelling data throughout 2024 into early 2025. This drug had good cellular potency, very good in vivo activity, and again, better drug properties in the likes of no CYP autoinduction based on what we can see, and a slightly better half-life as well. We've profiled ourselves, ORIC-944 versus both mevrometostat and obviously the first generation.
Based on that profile, we're as good as mevrometostat across the board and potentially better in certain aspects as well. This is just an in vivo model, again, in mice. What you're seeing here, this is a prostate-resistant model. Darolutamide by itself doesn't do anything. When you combine mevrometostat with darolutamide, you see a nice increase in the PFS benefit here. Obviously, when you're combining with 944 and darolutamide, you're seeing an incremental benefit even over mevrometostat data. All the preclinical profiling that we've done, comparing ourselves to mevrometostat, we feel that we're basically as good as mevrometostat, if not slightly better in certain categories as well. This is the early data set that really kind of reinvigorated the interest in PRC2 inhibitors in prostate cancer.
Pfizer originally presented this in May of 2023, and then they updated it in early 2024 on their Pfizer Oncology Innovation Day. These are two groups of patients. The brighter blue are patients that had failed abiraterone but had not seen an AR inhibitor. Here, when they were treated with a combination of mevrometostat plus Xtandi, they showed a radiographic benefit of 17.1 months, which you'd expect to see here with Xtandi alone is somewhere in the five to six months. They saw a 3x plus benefit in radiographic PFS. The second group of patients, the darker blue lines, these are patients that had failed Xtandi. Here, they showed a, when treated with a combination of mevrometostat and Xtandi, they showed a median PFS of 11.7 months.
What you'd expect to see here with Xtandi alone is somewhere in the likes of three to five months of benefit. The two criticisms of this data set was, one, it was a small N, and at the time, it was a single-arm study. There was no control arm. What Pfizer recently showed in early February of this year at ASCO GU was this randomized data set. These are patients that had previously been treated with abiraterone, and then they could have received chemo. It was not required, but they had the option to get chemo. In this study, about 44% of the patients were actually treated with chemo. What they showed here was a radiographic PFS benefit of 14.3 months in this patient population versus a control of 6.2 for a hazard ratio of 0.51, which is actually really great data.
Just as a point of reference, even if you looked at Pluvicto in a pre-chemo setting, so less heavily pretreated patients, they showed a radiographic PFS of under 12 months. I think it was 11.7 months. This is data that obviously was very validating for both mevrometostat for the target and a direct read through to ORIC-944. The reason this is important is basically, if you remember this slide on the biology here, being able to kind of re-energize the AR inhibitors. If you look at the AR inhibitor landscape, the three second-generation AR inhibitors, enzalutamide, apalutamide, and darolutamide, last year, they approached $11 billion in worldwide sales. As you can see at the percentages on the bottom half, they continue to grow. This is obviously a large market opportunity. The goal would be to combine with AR inhibitor in various different settings.
Pfizer has actually initiated two phase three studies late last year, and they recently announced a third phase three study in the metastatic CSPC setting. They are looking to move into earlier lines as well in combination with their drug enzalutamide. We initially showed some single-agent dose escalation data. Again, here since no one's really shown any robust single-agent data, the objective here was to demonstrate best-in-class drug properties. Half-life, we want to see good dose proportional exposure, the fact that we do not have any CYP autoinduction, and good target engagement. I'll go through these pretty quickly. As you can see here, we had a clinical half-life of 20 hours, which compares very favorably to tazemetostat and mevrometostat. Similar to mevrometostat, excuse me, we did not have any CYP autoinduction issues as well. Here, we just see some good PD markers.
This is an H3K27 methylation assay. This is monocytes in the blood. As you can see here, we're seeing maximal decrease in this assay at doses as low as 200 milligrams once-a-day dosing. We're seeing low interpatient variability. From a safety standpoint, again, this is single-agent. It was well tolerated up to doses up to 900, which is well beyond what we believe is the efficacious needed dose as well as from looking at PD markers as well. Where are we today? After completing the single-agent dose escalation, we did start in the second half of last year, we did start combination dosing with both apalutamide and darolutamide. We're currently continuing to explore doses for both combinations.
The goal here is to select the provisional RP2Ds in the second quarter of this year and then kind of move over to the right half of the slide here, which is the dose optimization. As you can see what's depicted here, we're looking at two different patient populations. We'll be looking at patients that had failed abiraterone, and we'll also be looking at patients that had failed the second-generation AR inhibitors like enzalutamide, apalutamide, and darolutamide. Just lastly, on one last point, earlier this year in January of 2025, we did present some early data. This is, again, just a caveat. This is a small N, N of six. We don't want to overportray this in any way. These are patients that had all failed abiraterone, and half of these actually saw chemotherapy.
What we were able to show in this small N here from a dose escalation with the combination with apalutamide is three out of the six patients. So 50% of the patients had a PSA50, and two out of the six patients, so 33% of the patients had a PSA90. If you go back and you look at the historical benchmarks, you would expect to see with enzalutamide or apalutamide alone is more along a PSA50 of 20% and a PSA50 of 5%. Again, caveat that it's a small data set, but it does look like it's trending in the right direction. From a safety standpoint, primarily grade one and two treatment-related adverse events, again, consistent with what you'd expect to see with PRC2 and AR inhibitors. Overall, the profile looked relatively favorable.
We'll talk about the milestones a little bit later in the presentation. I'll turn it over to Matt to cover ORIC-114.
Sure. Thanks, Dominic. I'll just cover a couple of the highlights for ORIC-114. This is our potential best-in-class TKI that we're developing for EGFR exon 20 mutations, HER2 exon 20 mutations, and atypical EGFR mutations. A couple of things about this program. This was a program we in-licensed several years ago, and there were already other molecules in development, especially for the EGFR exon 20 space. Our view at the time, which really hasn't changed over the last several years, is that we thought the key thing that was missing were two things. Most importantly, one is that most of the drugs in development were not designed to be CNS penetrant.
That has been a theme that has played out with essentially every other targeted lung therapy that we've seen before, including EGFR classical mutations, RET inhibitors, ALK inhibitors, ROS1 inhibitors. It has been shown that it is extremely important to have a CNS penetrant drug. We felt that was missing in this space, and so that we felt was one of the major flaws that we think that our molecule actually addresses. I think, too, our molecule was specifically designed for EGFR and HER2 mutations, is prospectively designed that way, and it's very targeted. I think from the preclinical data we've presented multiple times shows that our molecule is extremely selective for the mutations that we're targeting here. We believe that our molecule really solves the challenges out there. We've presented preclinical data multiple times. We won't go into kind of the detail here.
We are actively in clinical development. Here is a slide showing one of the main flaws, and I think this is shown with mobocertinib. This was essentially the first TKI that was approved in the EGFR exon 20 space. It has since been removed from the market because it failed the confirmatory phase three study. Essentially, all the data that they published really just highlights the flaws, not only with mobocertinib, but we have seen similar data sets from other molecules as well. This showing mobocertinib does not have CNS activity, and it has been shown preclinically as well as here is the clinical data showing that in patients that had some form of CNS metastases at baseline, essentially had half the objective response rate, which translated into even worse, 50% or greater on the PFS side.
What we've seen is other molecules have a very similar profile here. One of the ways that they've tried to address it is essentially excluding patients with forms of brain metastases from even enrolling in the studies. Most of the ongoing studies out there have extremely stringent criteria on what they actually allow into the studies. We think, again, so many patients in lung cancer have brain metastases just at baseline. We think that is a major problem if you can't address those patients, both that present with brain metastases when they get on therapies and then to developing them over time while they're on therapies. That highlights one of the major flaws kind of in the competitive landscape. That's essentially what we wanted to show with our clinical study with ORIC-114. Here's just a quick highlight of the dose escalation.
We've now since moved on to dose expansion, but we wanted to study our molecule extremely broadly. I think there's a couple of nuances with the trial design that is very different from how other people have developed their molecules. I think one, we are developing it relatively broadly in these mutations. It was designed to be a very potent and selective EGFR exon 20 inhibitor. That is obviously the place we started. We are also enrolling HER2 exon 20 as well as EGFR atypicals. The main thing here is we actually allow an extremely broad enrollment criteria for patients with CNS metastases. We allow, if you have active brain metastases, if your brain metastases have not been treated, you're actually allowed to enroll in our study. That's very different.
Most patients in other studies had to have had treated brain metastases with surgery or radiation and things like that, very stable brain metastases where we basically, again, we have a brain penetrant molecule, we believe. We really wanted to show that in early proof of concept in clinical studies. We allow that. The other thing that we allow as well is just other prior therapies. We're very generous on that as well. We even include other TKIs, especially even other EGFR exon 20 inhibitors. That is very rare from some of the other studies that we've seen. Now we are into dose expansion, and I'll give a couple of the highlights of the clinical data on what we've presented so far. Here's one quick snapshot looking at the waterfall, and this is in EGFR exon 20 patients.
As you can see, just very briefly, we do see a number of partial responses, including in patients that had prior EGFR exon 20. Staring at the bottom here, we also saw activity in patients with CNS metastases at baseline. This was early dose escalation data, but again, it kind of showed really nice proof of concept that we are seeing clinical activity in very heavily pretreated patients and also in patients with CNS metastases at baseline. We are very happy to see that. Excuse me. On the next slide, this is one case study which we think is essentially the perfect example of clinical proof of concept with ORIC-114. We did have one patient that came into our study with CNS metastases at baseline. The CNS metastases had not been treated, so they were considered to be active brain metastases.
There were four CNS target lesions at baseline. This patient had previously received chemotherapy. The patient had previously also received amivantamab, which is currently the other approved agent for EGFR exon 20, had failed both therapies and came on to our study during dose escalation. I think what we show here is what after cycle one, we saw a significant reduction in target lesions in the lung, and we also saw a significant reduction in target lesions in the brain. Within just a few months, this patient had a complete response, so 100% shrinkage of lung tumors as well as CNS tumors. At the time of this data disclosure, this patient was on study receiving drug for nine months on cycle nine. We think that this was extremely promising with very few tolerability issues.
This was something this type of patient was not able to enroll in any other study other than the ORIC-114 study, and we think really demonstrates differentiation of our molecule. Even to this day, we're not aware of another EGFR-targeted therapy that has shown active CNS metastases and a reduction after a single-agent therapy. We think this really stands out kind of in the landscape of other molecules that are in development. Real quick, just rounding it out, here's kind of a similar waterfall chart here. The difference being these are HER2 exon 20 patients, so we do see a nice waterfall. Again, similar types of trends. We are seeing partial responses during dose escalation in HER2, EGFR exon 20. Again, we see similar types of activity in patients with brain metastases as well. We have seen reports of reductions in CNS target lesions.
I think Dominic referenced this earlier in the presentation, but we announced this early this year. We actually formed a collaboration with Johnson & Johnson to study amivantamab, which is the currently approved therapy, in combination with ORIC-114. We are very excited by this combination that we started earlier this year. It is currently in a dose escalation, a very brief dose escalation in patients, and we are focused on frontline patients. This is a potentially first-line registrational pathway for the long term. This is a combination that others have not studied yet in the EGFR exon 20 side. A very different potential clinical development strategy for ORIC-114 going forward. We have seen similar types of strategies going forward in other lung cancer targeted populations. Johnson & Johnson, for example, is currently approved with amivantamab plus lazertinib in the classical EGFR mutation side.
They have also reported nice data with amivantamab plus lazertinib in the atypical population. This is a chance to kind of show the similar types of differentiation in the EGFR exon 20 space. We think the combination makes a lot of sense. I think from a preclinical standpoint, from a clinical standpoint, amivantamab is a bispecific antibody, so it targets EGFR mutations in a different way than a targeted small molecule covalent inhibitor like ORIC-114. The combination of both of them should give very broad coverage of EGFR exon 20 mutations. There have been a number of different types of mutations. One of the challenges with this target is there are a number of different insertion mutations that all have slightly different confirmation for the TKI. Having broader coverage with a dual-targeted agent makes a lot of sense.
There is potential for much more durable and deeper responses. We have seen that with amivantamab plus lazertinib in the classical EGFR setting. We think there is clinical proof of concept in combining a bispecific antibody with a small molecule TKI for lung cancer. We are excited by this type of collaboration. We will report the first data from this next year. Just as we think about market size real briefly, we are currently targeting about 7% of lung cancer if you add up the three different populations. Most other folks in the industry typically estimate that EGFR exon 20 is about 2%-3% of non-small cell lung cancer. HER2 exon 20 is similar. People estimate about 2%-3% there, and then about 3% or higher in the atypical side.
I think if you add all of those up, 7% is fairly significant when we compare that to other non-small cell lung cancer targeted therapies. I think any one of these populations is bigger than the prevalence of RET, which recently had some therapies recently launched there. selpercatinib is the leader doing about $400 million per year and growing very significantly. Of course, many people are familiar with the ALK space that represents about 4%-5% of lung cancer. Collectively, the markets that we are targeting potentially could be even larger than ALK. We think there is a nice commercial opportunity in the areas that we're targeting for a potential best-in-class small molecule. I'll pass it over back to Dominic.
Yeah. I think we'll cover the milestones maybe through the Q&A, Ami. Maybe we'll stop there, and I'll hand it over back to you.
Okay. Great. Thanks both. Maybe I guess most of my questions are focused on ORIC-944. You talked about the data that Pfizer had presented for mevro at the ASCO-GU meeting earlier this year. What was most surprising to you with regards to that data, and how does that provide validation to the class?
Yeah, that's a great question. Just to rehash that a little bit, just to remind everyone, these are patients that had failed abiraterone, and 45% of the patients had actually gone on to chemo. Pfizer was able to demonstrate a radiographic PFS of 14.3 months in the treatment arm versus 6.2 in the active control arm of enzalutamide, hazard ratio of 0.51. Honestly, this actually exceeded our expectations.
This data, from our standpoint, is potential practice changing, obviously subject to approval. When you look at the 14.3 months and you compare that versus other agents, approvals like Pluvicto in the pre-chemo setting, in less heavily pretreated patients, they showed 11.7 months. We think this data is very strong data. The other benefit of this is you're combining with standard of care. Obviously, the AR inhibitors, the second-generation AR inhibitors, represent $11 billion in sales. The ability to kind of piggyback off of that obviously presents a great opportunity. Overall, the data set was very, very strong. We think from a we were pleasantly surprised, I guess, is what I'm saying. Obviously, this is strong validation for mevrometostat. This is a direct read-through to PRC2 inhibition in combination with AR inhibitors. We believe it's a direct read-through to ORIC-944.
As you mentioned during the presentation, all the profiling that we've done comparing ORIC-944 to mevrometostat, in vivo, in vitro, we seem to be as good, if not slightly better than them on various fronts. I think the one area of potential differentiation is obviously the half-life. They have a four to five-hour half-life. They're doing BID dosing. The data they presented was at 1250 b.i.d., so it's two and a half grams of drug. Moving forward in the phase III studies, they're doing 875 b.i.d. We have the potential of doing a once-a-day dosing, which could obviously have its benefit as well.
Thank you. There was some conversation following their data readout around kind of some of the safety profile, particularly the heme and the GI tox. Can you comment on how much of that may be driven by simply the mechanism? Is that drug-specific, or is that just broadly kind of an adverse event profile of the class?
Yeah. Great question. Matt, do you want to take that?
Yeah. I think that's a great question. I would say probably answered a couple of different ways. I think there have been a number of PRC2 inhibitors that have went into clinical development in a lot of different indications. I think what is typically seen from an MTD standpoint in dose-limiting toxicities is typically hematological tox. Myelosuppression is kind of what you would expect with a PRC2 inhibitor. I think mevrometostat sees some of that. They saw some of that with their single agent. That would be completely expected. I think what is a question mark, I think, is kind of the GI toxicities.
I think that is somewhat where we have kind of focused on and really thought through as well. The one observation that Pfizer had made is essentially, if you were to dose it with food, is what they said, the 875, with food, they're able to lower the dose a little bit, but essentially get about the same PK. It looks like maybe the Cmax is a little bit lower, AUC is better with food, but their claim is that it essentially mitigates a lot of the GI tox. That is kind of one question. If you can fix GI tox with some food, with some formulation work, in some ways, that might lead you to believe that maybe it's not exactly on target. It could be somewhat a function of what Dominic said.
They're giving two and a half grams of drug per day, probably for a long time if the PFS benefit was or the PFS magnitude is 4.3 months. It could be either. The right answer is probably a little bit of both. We also know enzalutamide, single agent, also has GI tox. Very low grade, kind of grade one, grade two is what you typically see with an ARPI inhibitor. If mevrometostat could be adding a little bit to that, that is quite possible. The fact that they're able to improve it with formulation and food, it could also be just drug-related as well. Yeah. It would be what will we see?
I think time will tell, but that's obviously something that, can we improve on the GI and the heme tox, I think would be kind of an interesting question that I think our data will show us that eventually.
Yeah. We spoke to the PI after the presentation. Basically, with the dyschezia, they actually said that they were able to resolve it with saltwater rinses and things like that, so it wasn't that bad. Yeah, again, we heard that with the lower dose, the GI, and they stated this in their slide, the GI was better.
Yeah. Okay. Can you talk about sort of the PSA50 data that we're seeing with this class and how informative it is with regards to the ultimate kind of median PFS that we would see? Also, just going back to the data that we've seen from your drug, does that give us some insight into potential differentiation?
Yeah. No, that's another great question. I think our view here, and I'll start and Matt, you chime in, is basically it does provide validation for the PRC2 complex, right? Pfizer's been able to show that in the PRC2 complex, when you see PSA responses, that did translate into PFS benefit. Comparing that to us, I think, is relevant. I think when you start comparing different mechanisms, then it gets a little more complicated, like showing the PSA50 for Pluvicto, which is a radioligand versus us, or T-cell engagers versus a PRC2. It's just different biology. It's a very different MOA. That becomes a little more complex.
Comparing what Pfizer has shown from a PSA and the translation of that to PFS, I think that is very relevant. That is kind of a read-through to us, hopefully, as well.
Maybe sort of extending from what I was trying to ask also is you talked about kind of some of the differences for 944 relative to Mevro. We can sort of just hypothesize until we see the full data, but where do you see some of the differences potentially playing out in the clinic, particularly on efficacy or safety?
Yeah.
Maybe a related question. Do you think you need to be better to be successful commercially?
Why don't you start off, Matt?
Sure. You asked a couple of good questions, slightly different. The last one is probably the easiest one for sure, is, do we need to be different?
I think our view is we don't need to be. I think if every bit is good as mevrometostat, I think that is a great situation to be in. I think the reason why we say that with decent conviction is because the prostate cancer market is so substantial. From what we have seen in prostate cancer before, both Dominic and I were at Medivation with enzalutamide, which was the second kind of ARPI to launch after abiraterone. Now that we've seen that full story play out from abiraterone to enzalutamide to apalutamide to darolutamide, if you look at the clinical data for all four of those ARPIs, they're very, very consistent, both in terms of RPFS, PFS, OS, hazard ratio. They're all basically on top of each other. There's very minor nuances potentially in safety profile and dosing and things like that.
All four of them have been wildly successful. Somewhat surprisingly, even apalutamide and darolutamide are easily blockbusters now, even though they launched seven, eight years after abiraterone and enzalutamide. I think just looking at that data set in the exact same patient population tells us that you could be second, third, fourth market with very little differentiation and have pretty significant commercial success. I think that kind of gives us confidence. That being said, I think what we hope and what is we are differentiated. I think we have a few things going for us. I think one, our molecule does seem to really have great drug properties that we've kind of shown in our single agent phase one.
We are dosing QD, and it seems that we have kind of 20-hour, 24-hour half-life, which gives us confidence that we can maximize target engagement for a very long period of time without using very significant drug doses. We think that bodes well. I think if you look at kind of other drugs that can have that profile in other spaces, in general, that's a good thing if you can dose your molecule and have strong target coverage. We think that could play out in the long term, potentially having better efficacy, potentially better safety as well. There are areas to improve, I think, on the Pfizer safety profile, again. I think there's a couple of potential ways to win. The other way as well is at some point, we are currently doing combination dose escalation with apalutamide and darolutamide.
At some point, we will select probably one of those to go forward into at least our first phase three. Is there a potential benefit from selecting a different ARPI inhibitor, different from an ARPI? Potentially so. Pfizer is tied to enzalutamide. There is likely significant drug-drug interaction with that combination. That might not be the case using a drug that's metabolized different, like darolutamide. There are a couple of different options for us to kind of have a differentiated regimen as we think about moving into phase three. Again, similar to before, we need to generate more clinical data to give us the confidence that we might have something differentiated. I think Dominic also showed a quick preclinical slide.
When we've looked at a lot of the preclinical data, a lot of our in vivo data looks to be at least as good, if not a little bit better. I think Dominic showed a treatment refractory mouse model that outperforms single agent darolutamide. The combination of ORIC-944 seems to have a benefit over mevrometostat plus darolutamide. We have kind of incremental preclinical data that suggests maybe there is some differentiation there, but I think time will tell again. Sorry, I'll stop there. Dominic, did I miss anything?
No, it's perfect.
Okay. Maybe this is a good time to kind of talk about just the data readout later this year and the decisions that you kind of have coming up with regards to which combination you're going to go ahead with. Maybe kind of just summarize that for us as to when we'll see the data and what the path forward would look like.
Yeah. I'll start that, and Matt, you add on anything. With regards to ORIC-944, the current guidance is we'll provide an update in the first half of 2025. What we said there, it'll be around 12-15 patients' worth of data. Again, this is dose escalation data. Kind of some of the questions you asked earlier, the focus is really going to be on PSA response. Pfizer kind of gave us a benchmark on how to measure our program against theirs. That will be kind of the line in the sand that we'll look to kind of achieve or hopefully exceed in some sense.
We want to at least be as good as Pfizer when we think about that data set from a PSA response. In the second half of the year, we'll also have a second update, again, from the dose escalation. Here, we said it'll be 20 patients -25 patients of data. That's doubling the number of patients we'll show you in the first half. Lastly, we said we'd have the dose optimization data in either Q4 of this year or Q1 of next year. We've got all three data readouts in 944 in the next 12 months, which we think, given that Pfizer's got kind of a benchmark for us, this should be compelling data to compare ourselves versus Pfizer in this setting.
Maybe just in terms of the two readouts, is one going to be informative of the other, the 12 patients- 15 patients versus the 20 patients-25 patients? How much data do you need to see to really get to the point of, "Okay, we're going to go ahead, move forward with one of the two combinations"?
Yeah, that's a great question. I think the data will be we showed you six patients in January. We're showing you double that here, and that will include the six patients from January, just to be clear. Obviously, the data set later in the year, doubling that again, getting the 20-25 patients. I think all this is really important data. Obviously, we want to look at it. Obviously, we want to make sure that we're seeing any surprises on the safety side as well.
The focus, obviously, would really be, because this is dose escalation, the decision to move forward. Obviously, we will look at the dose optimization data. We'll look at the PSA50s. Again, it would be too early to look at durability. We're not going to have full mature PFS data. If we were to do that, we wouldn't be able to start the phase three study until 2027. Our goal is to start that first phase three study in the first half of 2026. We believe we'll have sufficient data, obviously, prior to starting that study to move forward. We just can't afford to wait for that fully mature data. Right now, if you look at what Pfizer has said, they started that first phase three study in October of 2024. They said the primary completion date is late 2025, and they're expecting to launch that in 2026.
From our timing standpoint, if we start that study in the first half of next year, we're basically about two years behind them, which is not very long, right? We're in a really good position, and we don't want to lose that kind of fast follower position. That's why we're doing it this way. Again, I think pending any surprises, that's kind of the current plan from a move forward to the phase three. Obviously, we have to select the RP2D for 944. As Matt said, we're not going to move forward with both apalutamide and daralutamide. We'll have to pick which lutamide we want to move forward with. Obviously, there's a lot of considerations. We'll look at the data based on everything we've seen today. There's no reason one should be better than the other.
They're both great drugs, so we should have the option to pursue either one. Some of this will be conversations with both J&J and Bayer, which one we're going to move forward with. Our position is to start that study in the first half of next year on our own. Obviously, a lot of things could happen, but that's our kind of base case scenario.
Okay. I'm being told that we are out of time, so I think I've got to close here, but this was a great conversation. Thank you so much for participating.
Great. Thank you for having us. Okay.