Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. Happy to introduce and welcome Jacob Chacko, CEO, and Dominic Piscitelli, the CFO of ORIC. We're going to do fireside chat format, so maybe for those who are new to this story, if you guys can give a one-minute intro to your programs, and thanks for joining us.
Sure. Thanks for having us, Maury. Happy to do a quick intro. ORIC stands for Overcoming Resistance in Cancer. In a nutshell, that's the mission of the company. We're focused on solid tumors, specifically prostate cancer and lung cancer. We have two different programs that are now approaching the start of phase III studies, so pretty far along in terms of clinical development. Both of those have best-in-class potential, and I'm sure we'll get into all the reasons why we feel very strongly that they have best-in-class potential. The first program, rinzimetostat, is a PRC2 inhibitor that's being developed in prostate cancer in combination with various androgen receptor inhibitors in prostate. The second program, enasertib, is a brain-penetrant TKI for two different populations within non-classical EGFR mutations, and its claimed differentiation is all around that CNS activity.
Got it. Yeah, it's a great intro. I wanted to jump right into the update from Fulcrum, which was announced on Monday. It's obviously top of mind right now. Could you speak to their recent update regarding their drug and potential implications for rinzimetostat?
Yeah. It's not always that we're asked to comment on sickle cell disease, but in the case of Fulcrum, because the target that they're working on is the same target that we're working on, but it's obviously in two different disease states. I think there's some questions that are natural about what are the potential read-throughs. I guess first of all, just to level set on what Fulcrum said in their press release, so they specifically called out the fact that the risk-benefit calculus in sickle cell disease is what FDA was focused on. The other thing is they reminded folks, I think, that they had seen what sounds like fairly significant preclinical malignancy findings in the preclinical tox studies that were done. The other thing they called out was some level of similarity or some kind of similar patterns that were seen with tazemetostat.
Essentially, tazemetostat, like pociredir, which is Fulcrum's drug, seemed to see a fair bit of toxicity or malignancy signal in those preclinical tox studies. Of course, Taz also had some of that in the clinic as well. Those were the pieces that we were able to glean out of their press release. Look, we take these things very seriously, but at the same time, we think that this has limited implications for ORIC for a number of reasons. There's some key differences. First and foremost is the risk-benefit. These are always a question of risk-benefit when you think about the benefit that a therapeutic intervention is giving to a patient versus the risk that they are taking on. Clearly, the deck was stacked against Fulcrum in certain ways because of the disease they're talking about.
They're talking about sickle cell disease. It is a bad disease, but it's not largely a fatal disease. It's a disease where young patients get the disease, and then if you're going to give them chronic treatment, they're going to be on therapy for decades on that chronic treatment. It's a population that already is susceptible to other malignancies. They have a higher rate of other malignancies, including heme malignancies, which is exactly the kind of secondary malignancies that Fulcrum was seeing in their preclinical experiments. The risk-benefit is really stacked quite heavily against them in that sense. Now, in contrast to all of that, if you compare rinzimetostat, which is our PRC2 inhibitor that we're developing in prostate cancer. First of all, we're developing it in prostate cancer. That is a fatal disease.
The risk-benefit profile is quite different there. I'm going to talk for a little bit here, if you'll allow me, Maury, just to expand on that because I think it's important for people to understand some of these nuances. The other fact is with rinzimetostat, we've run four-week tox, we've run 13-week tox studies. We've seen no malignancy. None. We've now run the drug in the clinic in both single-agent experience as well as a combination experience in over 100 patients, no malignancy. None. The set of facts and circumstances are quite different, obviously, between the two drugs, what they've observed both preclinically, what they've observed clinically, and then like I said, the ultimate fail-safe is the risk-benefit in the disease areas that we're talking about. Let's expand on that for a second as we think about the risk-benefit.
This is important for people to understand. FDA is a well-run agency. They are very nuanced in the way that, aside from the disarray at the top, the core of FDA is a well-run agency. They're very nuanced in the way that they go about understanding risk-benefit across all disease types. One thing that's important for people to understand is FDA is not just retrospectively looking at data sets and then trying to analyze risk-benefit across two different data sets. They have prospectively laid out for all drug developers ICH guidelines. Those ICH guidelines, there's one set of ICH guidelines for oncology therapeutics. There's a different set of ICH guide that's called S9. There's a different set of ICH guidelines for everybody else that's not oncology.
The reason for that is that recognition up front that the risk-benefit is quite different for oncology interventions than it is for non-oncology interventions. If you look at the ICH S9 guidance, what it tells you is that if you want to, as an oncology therapeutic or oncology company, if you want to do a first-in-human study, you need to have four weeks of toxicology work completed. If you want to do a registrational study, and that to enable an eventual NDA, you need to have 13-week tox completed. In the case of non-oncology indications, in many cases, you have to have up to nine months of tox completed. You can see right there the distinction that they're drawing in terms of how they treat oncology versus treat non-oncology. That's on general FDA approach to these kind of questions of risk benefit.
Now, let's move into the specifics for ORIC, because I think the people who've been following our story closely know that we're about to start our phase III study, the first phase III study, HIMALAYAS-1. Obviously, in advance of the impending start of HIMALAYAS-1, you can imagine that, and now I can confirm for you that over the last one to two quarters, we've had significant interactions with FDA, culminating in an end of phase I meeting that is complete, finished, done, and behind us. That end of phase I meeting took place within the last few weeks. Again, very real time. FDA has had the benefit of everything that they've been discussing with other companies with this target. Folks will remember that there was some tazemetostat news that came out in the March timeframe around the same topic, secondary malignancies.
We've had multiple interactions with the agency after that tazemetostat news came out. Our end of phase I meeting took place after that tazemetostat news, like I said, within the past few weeks. The point of that end of phase I meeting was threefold. It was, number one, to get sign-off on our proposed protocol for the Himalayas-1 phase III study. Number two, it was to get sign-off on, for Project Optimus purposes, our proposed recommended phase III dose for the Himalayas-1 study. Number three, it was to identify, is there any other remaining prerequisites for us to do from FDA's perspective before we start that Himalayas-1 study to enable the ultimate NDA? The answers to those are all now finalized, which is the protocol is final.
The recommended phase III dose of 400 mg once daily for rinzimetostat in combination with darolutamide, the label dose of darolutamide, that dose is final. They've signed off on that as well. There are no prerequisites from FDA's perspective that they have requested of us before we start that Himalayas-1 study. I could not state it any more definitively that the read-through from the news and the noise you've heard in the space is limited with respect to ORIC. Now you also have the confirmation that the end of phase I meeting has taken place, is done, and we are good to go for the start of Himalayas-1, which I think is probably the most important takeaway for people.
I always caution investors on this topic is just take a huge step back and just put yourself in the shoe of a patient who's got metastatic prostate cancer, and you have 100% chance of dying from that prostate cancer. It's just a question of when that's going to happen, it's not if. If the decision that you're faced with is a low risk of a secondary malignancy that pops up at some point in your therapy, you're still going to take that risk benefit all day long.
There's no way that I can sit here and promise you that we're never going to see a secondary malignancy with rinzimetostat. I can't promise you on Pfizer's behalf that they're never going to see it with mevrometostat. The point is, as long as it's low rates, the risk-benefit profile is always going to be in the favor of a therapeutic intervention that's giving meaningful duration in prostate cancer.
Right. Yeah.
I hope that answered your first question. I know you have others.
We've got other questions, too, but that's really helpful perspective and overview. I think some of the doc feedback that we've gotten, which hasn't been recent, post the Fulcrum update, but before that, it seems like, I think oncologists, especially ones participating in this space, are familiar with this risk of the secondary malignancy. For prostate cancer patients, it's not a huge deal breaker for them. They're still enrolling in the studies.
It's an excellent point you bring up, Maury, and the thing is that folks should go back and refresh themselves by going back and looking at the labels of drugs that are the most frequently prescribed drugs in the prostate cancer space. You will see that the AR inhibitors, enzalutamide, you'll see Pluvicto, the PARP inhibitors, chemotherapy, they all have a low risk of secondary malignancy. That's why I think that clinicians in the space are quite used to it. Again, it all comes back to the risk benefit.
Yeah. I guess taking a step back, though, both your drug and pociredir from Fulcrum, they target the EED subunit. I guess why would you not see the secondary malignancy signal from your drug versus theirs?
Yeah. The way to think about this risk of secondary malignancy, this doesn't apply just to PRC2, the target that we're talking about here, but in general, there's a lot of factors at play that could determine why one drug sees a signal and another one doesn't. It's all on a risk spectrum, Maury. In this case, I can rattle off a few different factors that you got to think about. This is not just I'll broaden your question to not just the comparison between us and pociredir, but also to include tazemetostat in the equation, mevrometostat in the equation as well. That's Pfizer's drug. What you have to think about is a couple things on the risk spectrum. One is when you talk about PRC2, that's a complex that has different subunits. One of the subunits is EZH2. Another subunit is EED.
We are targeting EED. Pfizer's drug, mevrometostat, for example, is targeting EZH2, as did tazemetostat. As you mentioned, pociredir is an EED inhibitor. When you look at the gene knockout studies, the gene knockout studies would suggest to you that when you knock out EZH2 selectively, an EZH2 selective inhibitor seems to be more prone to secondary malignancies than either an EED inhibitor or a dual EZH1/EZH2 inhibitor. There is something about leaving EZH1 intact that seems to lend itself to a greater predisposition to secondary malignancy. That's not the full answer because there's obviously a risk spectrum, and it doesn't mean that an EED inhibitor is never going to see it. Fulcrum does seem to see it. As you think about what are some of the other factors, age seems to be a factor.
Age of the patient, age of the animal species. When you look at the tazemetostat experience, valemetostat experience, what sounds like the Fulcrum experience based on what they've written in their 10-K, it seems to be the case that the mouse model or the rodent models are more sensitive in juveniles than they are in adults, meaning that it takes a lower dose in the juvenile animal models to see this malignancy signal pop up than it does in the adult model. Valemetostat, for example, it sounds like that was a drug that saw the tox in juvenile tox studies, but not in adult tox studies. There's a distinction there as well around the age, and that would apply in the clinic as well because of that age difference. There's a PK difference, which is the half-life of these drugs.
Keep in mind, the half-life is not the same for these drugs, and to the extent that Cmax is kind of linked to the toxicity, this chronic tox, it certainly is linked to acute tox, but if it's linked to chronic tox as well, our half-life for rinzimetostat is 20 hours. Fulcrum's half-life is about six or seven hours. Mevrometostat, Pfizer's drug's half-life is about four or five hours. Tazemetostat's half-life is about one to two hours. My point being that those other three drugs I just mentioned have half-lives that are six hours or less. Rinzimetostat has a half-life that is 20 hours. It means we'll have a lower Cmax, and that might lead to a difference in why you see something with one drug versus not with another.
The final piece, it's nothing to do with the mechanism at all, but could just be tissue distribution. Different drugs will distribute to tissues differently and no two drugs are going to have the exact same tissue distribution. Depending on how much or how little gets into the bone marrow, you could see differences in the way that these profiles shape up. There's no way that you can sort of just formulaically paint the entire PRC2 class with the same brush.
Got it. Maybe going back to your focusing on the age one, for your preclinical studies, you haven't seen any signal there, but were those younger mice, older mice?
Prostate cancer is a disease of very old gentlemen, so there's no juvenile tox studies that were done-
Yeah. Okay.
...nor that are needed to be done.
Got it. Okay. All makes sense. Let's shift gears. Let's talk about the phase III study you mentioned, HIMALAYA. What are you projecting in terms of the phase III timelines, and have there been any changes to that?
Yeah, I probably belabored your first question quite a bit to emphasize that there are no changes to our HIMALAYA base case, which continues to be the case that we've said the public guidance is we'll start that study in the first half of this year. The start is imminent. Look, June, July, if it starts in the next month or two, we're on track for that kind of a start. I think what I want you to hear from me is that's just a question of literally site logistics, getting through internal review boards and things like that, not anything to do with big showstoppers like FDA guidance or feedback on any of this.
In terms of the overall timelines, it continues to be what we've articulated before, which is it's roughly a year and a half, call it, plus or minus, so 18-20 months from the start of the study to getting the top-line answer. Very consistent with the timing that you've seen from MEVPRO-1. Given that Our study is going to start imminently in HIMALAYA, as I'll just remind folks, that's in the same setting as MEVPRO-1, which would be castration-resistant prostate cancer in patients who have already progressed on abiraterone and could have had up to one prior line of chemotherapy. We'll have a treatment arm, which is rinzimetostat in combination with darolutamide. Control arm will be physician's choice of an ARPi switch or chemotherapy, 600 patients. Again, very sim overall, so 300 in each arm. With an 18- 20-month timeline, that means top-line answer in early 2028.
Got it. Okay. That's helpful. Pfizer is supposed to have a data update from their phase III study, MEVPRO-1, which you mentioned, which is assessing mevrometostat plus enzalutamide versus enza or docetaxel in post-abiraterone metastatic castration-resistant prostate cancer. It's going to happen this year. How do you view the potential scenarios for outcomes and implications for your program?
Yeah, look, I like to be a caveman about it. I'm just simple on these things.
Okay.
I think the scenarios, the way I look at it is basically four scenarios, if you want to simplify it, which is they easily win, they barely win, they barely miss, or they completely miss. I think just given the strength of the data that you've seen at this point from them across multiple phase I data sets, across a randomized phase II data set, the strength of the data you've seen from us in combination, our combinations of rinzimetostat in combination with either darolutamide or apalutamide, I think that fourth scenario is almost off the table at this point in terms of a total miss.
It's one of the other three scenarios. I think the PTS of that study is quite high, just given how much data has been generated already, including in a randomized phase II experience. I guess we'll wait to see which of those it ends up being.
Got it. Okay. Any more perspective into timing?
For timing of their study?
Yeah.
I'd be guessing just the same as you would. I think their public disclosures continue to be that it's coming in 2026.
Yeah.
I think if you look at the primary completion date of their study, it's listed as, I think it's mid-July.
Yeah.
If that's the case, our understanding is that based on their public commentary, they completed enrollment in that study early this year. If you just do the trial timelines, it sounds like it's headed towards that mid-July primary completion date, which means you get the events a little sooner. We might have the answer in the next month or so. If it takes a little longer, then maybe it's into July, August, or September, so we'll see. That's my best guess estimate, but their official guidance, I think, continues to be sometime in 2026.
Got it. Yeah. Makes sense. Okay, you guys had a data update in late March. You reported encouraging dose expansion data for your rinzimetostat plus darolutamide combo program. What are the three or five key takeaways investors need to know about the data you report there?
Yeah, given the time remaining, I won't.
Okay
I'll limit it to not five takeaways, but basically what I'll say is the thesis is playing out exactly as we had predicted probably 18-24 months ago, which is that I already mentioned Pfizer's got about a four or five-hour half-life with mevrometostat. Rinzimetostat, our drug, has a 20-hour half-life. The thesis has always been that with an epigenetic modifier like this, you want to cover target for 24 hours, including at your Cmin. I assume Pfizer is doing that. They've never confirmed that, but I assume they're doing that. Let's give them the benefit of the doubt. I know that we are doing that with rinzimetostat, and so that would lead you to believe that the two drugs could be equally efficacious if indeed they are covering target for 24 hours.
It seems to be the case in the early data from them and from us that they're tracking to the same places in terms of efficacy. Where the difference should come out is on safety, and the reason for that is with a four or five-hour half-life, you can just imagine their PK curve. In fact, they've told you that this is happening, that they get two big Cmaxes during the course of the day. The toxicity is Cmax-driven. With a 20-hour half-life like we have, we don't have that same Cmax-driven toxicity that they do. Both compounds see on-target toxicity, which is heme tox and GI tox, which is what you would expect, but Pfizer sees a higher frequency of it and a higher intensity of it than we do with rinzimetostat. That's one big difference.
Another big difference that I don't think people fully appreciate, Pfizer hasn't commented a lot on, is they certainly have a DDI when they give mevrometostat with enzalutamide, which is their AR inhibitor. The reason for that has to do with enzalutamide. Enzalutamide and apalutamide are two of the big three AR inhibitors. They're both global blockbusters many, many times over. They're great drugs, have done great for patients. One of the issues with both of those drugs is that they are CYP inducers, so they push down the exposure of many drugs that you would combine with them because so many drugs are metabolized by the CYP enzymes.
Certainly, you can even see in our own phase I data set, you can understand what that DDI is because we told you that we're dose optimizing doses of rinzimetostat in combination with apalutamide that are 2x the level of dose that we're optimizing for rinzimetostat in combination with darolutamide, meaning there's a 2x DDI. Pfizer almost certainly has that same level of DDI when they're combining mevrometostat with enzalutamide. We don't have that DDI with darolutamide because darolutamide is not a CYP inducer. What they're having to overcome is two things. One is the relatively short half-life of four or five hours, and the second thing is the DDI with enzalutamide, which is why their phase III dose is almost 1.8 g of drug per day split into two different doses.
It's 875 mg BID in a fed state because apparently they have a very large food effect. That PK alone just tells you how the story is going to play out. In the data that you asked about the takeaways from rinzimetostat that we presented on March 31st, what you saw was efficacy that was very much in line with Pfizer's efficacy at all the benchmark, landmark benchmarks that we could do at that point because we had five months follow-up at that point, and the safety was clearly highly differentiated for us with the rinzimetostat combination with darolutamide. That was not a small data set because we actually presented two different populations for purposes of the safety, so you could really understand it. It was upwards of 75 patients. That safety difference is quite stark.
Got it. That's helpful. Yeah. I think in your data update, definitely one of the key takeaways is that there's a safety differentiation between the two programs. How do you think that could play out on efficacy in your study? What are some ways that could translate?
Look, the optimistic side of me would hope that the safety difference translates into an efficacy difference as well in a phase III study. That's the kind of thing that it's hard to tease out in a phase I, but in a phase III, where patients are really not supposed to come off drug except for progression because the primary endpoint here is radiographic PFS. If someone runs into some safety issue, you'll get things like dose reductions or discontinuations. Otherwise, you'll try to keep them on drug, and maybe the optimistic side of me hopes that that would result in perhaps a lower dose intensity for Pfizer in their dosing than we would experience with ours because our safety profile was so clean. Look, I don't want to hang my hat on that, we'll see if that plays out.
In CSPC, castration-sensitive prostate cancer, that should absolutely play out, meaning a safety benefit should play into a PFS benefit because in CSPC, you're expecting patients to be on not for a year, but rather three, four, or five years. That actually, that safety benefit could bleed into an efficacy benefit as well. The key question we got after the rinzimetostat update in Q1 was. Let's say in CRPC, the way this plays out is that Pfizer and we both get approved and the efficacy looks roughly the same, the durability looks roughly the same, but the safety looks the way it did, which was starkly different, i s that enough of a difference, versus Pfizer, to be commercially competitive, especially if we're coming 18-24 months after them to market?
I would tell you the answer is staring you in the face, which is darolutamide. Darolutamide was the third of the big three AR inhibitors that was approved. People forget enzalutamide was approved, that was the first one. Dominic says he developed it at Medivation, his colleagues there worked on Xtandi. It was approved in 2012. Apalutamide, the second AR inhibitor, was approved six years later, darolutamide came even after that, an additional year later. Darolutamide came to market seven years after enzalutamide. All three of those drugs I mentioned already are blockbusters many times over. Darolutamide is run rating at $3.5 billion of sales per year globally, growing 50%-60% a year.
When you ask the physicians what's the difference in these three drugs, they will all tell you they have their own personal preferences, but the efficacy is the same for those three drugs in all the settings in which they've been tested. What is different is on the safety tolerability side, they will rank order darolutamide at the top, then apalutamide, then enzalutamide. That's where a safety difference alone is enough.
We've done our own independent research. We've had consultants do their own independent research showing a blinded TPP or target product profile of two PRC2 inhibitors, same PFS, different safety profiles, with the safety profiles being, on a blinded basis, of course, Pfizer safety profile and our safety profile. Product B, which is rinzimetostat in combo with daro, wins every time in terms of the one that they would choose, and they always cite safety as the reason for that.
Got it. That's helpful. The primary reason why you're seeing better safety is probably because of the half-life being much longer.
Yeah, exactly. Back to what I said. Yeah, the half-life and therefore, less Cmax-driven-
Yeah
...toxicity. A second benefit long term will be the darolutamide combo partner-
Right. Yeah.
will shake out as well. We'll get a benefit in terms of both parts of the combination.
Okay. When you're comparing your data set versus Pfizer's data set, phase II data set, how do you think about just the relative severity or sickness between your patient population and the Pfizer patient population?
I was talking to some investors earlier today who are in the room right now about this, that we are not supposed to do cross-trial comparisons. We all do those cross-trial comparisons. The reason why that's a hazardous task is you just look at what you just cited, Maury, which is Pfizer's phase I data that everyone keeps trying to benchmark us to, and we're happy to go along with that game and do the benchmarking. They allowed patients who were prior abiraterone, so all their patients had prior abiraterone, just like our study. All of their patients could've had prior chemotherapy, just like our study. In both cases, roughly 40% of the patients had prior chemotherapy. And in Pfizer's case, that's where it stopped. No other therapies, nothing else allowed. For us, anything else was allowed. We had a whole host of things.
There was IO agents, there was PARP, there was investigational agents, and what it results in is, as you would expect, is Pfizer's randomized data was a lot cleaner. They had a incoming PSA of 15 because of the clean inclusion/exclusion criteria. Because we allowed a lot more, our PSAs were, I think, 25 or 26 on the incoming baseline PSA. Those are meaningfully different. I would say that Pfizer's 15 incoming PSA is very much in line with all the recent phase III prostate studies that have been done, and then ours was obviously higher than that, but that is what it is in a phase I study.
Got it. Yeah, makes sense. Maybe briefly comment on just kind of the paradox with the mechanism where with targeting PRC2, that can restore AR signaling, and that could lead to an increase in PSA. Do you see that in your studies? Are you going to have to educate doctors on that?
Yeah. What you're referencing is the fact that PRC2 is an epigenetic modifier. One of the targets it hits is called KLK3, and that's the gene responsible for PSA. As a single agent, we actually saw PSAs shoot up when you gave the drug. We've all been trained to think of PSAs as this early proxy of activity in prostate cancer. You all have to keep in mind, it's a proxy measure. That is where PSAs have that kind of complicating factor, is here with this mechanism. Thankfully, we see with the Pfizer data and with our data that in combination with an AR inhibitor, the collective action is able to drive PSAs down.
Hopefully there's not as much education that we have to do with doctors, but you certainly need to educate them on you don't want patients coming off for a rising PSA alone. That wouldn't be a good thing to do. We got questions about that, too, because in the phase I experience, you may see patients come off for a rising PSA because patients and physicians have been trained in the prostate space to say, well, the PSA is not going down, or, it's going up. I'm therefore going to try a different therapy. In a phase III, that doesn't happen. The reason is PSAs in a phase III are drawn at the site. The blood is drawn at the site.
The PSA is read centrally, and it is never reported back to the physician or to the patient because people understand this dynamic that you don't want people coming off for a rising PSA, and that's why you don't even report it back to the treating physician. That's how the dynamic gets sorted out in prostate studies. That's been for a long time now.
Got it. Maybe in the last couple seconds, for the update that you're going to have second half of this year, what's going to be included in that? Is the disclosure, is it going to be influenced by MEVPRO-1? How are we thinking about that?
Yeah, Maury, I'll take that one. The second-half update, we've intentionally called it a program update to preserve some optionality there. That could be a number of things. That could just be an update on the current phase III study that we anticipate starting Himalayas-1. That could be our thoughts on a potential second phase III study in prostate cancer, or it could be some color on MEVPRO-1. The last thing, it could include some more mature data from the data we presented earlier in the year. That's a little bit to be seen.
Okay. Understood.
Maury, sorry, I know we're out of time.
Yeah.
I just remembered my very long filibuster to your first question.
Okay.
There was one other thing I did want to make very clear because I do think it's relevant. Not only is the end of phase I meeting done and we have clearance to move forward into the phase III study, but I also want to make very clear the topic of secondary malignancy was discussed at length with FDA. This is not like there's an unspoken topic that hasn't been discussed yet. It has been discussed at length with FDA.
Got it. That's helpful. Okay, in closing, since we're out of time, maybe if you want to just comment on enozertinib and just the second-half update and then key catalysts I had investors should be focused on.
Second-half update, we have a pretty comprehensive update on the enasertib program, we'll have three cohorts of data. Each of the cohorts will be around 20-25 patients worth of data. We'll have, again, first line EGFR exon 20 as a monotherapy, first line EGFR atypicals as a monotherapy, and then we'll have the combination with amivantamab as well. The bar there, generally speaking, we want to see a systemic response of 60% or better for each of those.
Got it.
My only plea there would be please, please, people do some work on our second program.
Okay.
It is a highly differentiated program, and we are really looking forward to presenting that data in the second half of this year because it's a space where patients are really underserved by a well-tolerated regimen that is brain penetrant.
Got it. Jacob, Dominic, thanks so much for joining us today.
Thanks for having us.