Good morning, welcome to the IDEAYA Biosciences Darovosertib clinical data and regulatory update call. At this time, all participants are in a listen-only mode. An Analyst Q&A session will follow the formal presentations. As a reminder, this event is being recorded, a replay will be made available on the IDEAYA website. I would now like to turn the call over to your host, Yujiro Hata, President and Chief Executive Officer. Please go ahead. Great. Thank you so much for the introduction. We're absolutely thrilled to welcome everyone to our phase ll clinical data update on the Darovasertib and Crizotinib combination and to walk through the Accelerated Approval trial design in first-line metastatic uveal melanoma based on our successfully completed Type C meeting with the FDA. The company will also provide a clinical data update for Darovasertib in neoadjuvant uveal melanoma. We will be making some forward-looking statements today. Please refer to our SEC filings as appropriate. To begin, I wanted to provide a special thank you to all our online participants and our KOL guest speakers. Today, we have a phenomenal lineup of international guest speakers that include Dr. Meredith McKean, the Director of Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, Professor Anthony Joshua, the Head of the Department of Medical Oncology at The Kinghorn Cancer Centre in Sydney, Australia, and Professor Mark Shackleton, the Director of Oncology at Alfred Health, Melbourne, Australia. Today's update is a culmination of over 5 years of innovative research in understanding the fundamental biology of uveal melanoma and demonstrating IDEAYA's organizational commitment to advancing first-in-class therapies that address the highest unmet medical needs in cancer. Due to the mechanism of action of Darovasertib as a PKC inhibitor, it has the opportunity to broadly impact uveal melanoma. What makes uveal melanoma genetically unique is that over 95% of patients harbor an activating mutation of GNAQ, GNA11, or a further upstream mutation that is believed to activate the PKC signaling pathway. Therefore, in the truest sense, the indication is the diagnostic. As demonstrated on the bottom left, Darovasertib monotherapy drives complete regressions in a primary uveal melanoma in vivo model, providing the scientific basis for a monotherapy clinical development focus in both the neoadjuvant and adjuvant uveal melanoma settings. Through our translational research efforts, we discovered specifically in the metastatic setting of the liver, a direct correlation between MAPK pathway activation and disease progression in our Darovasertib phase 1 clinical trial, providing the scientific basis to pursue the Darovasertib and Crizotinib combination clinically in the metastatic setting. As noted earlier, we successfully completed our Type C meeting with the FDA. I'm delighted to introduce Dr. Daren Beaupre, our Chief Medical Officer, who will walk through the Accelerated Approval trial design in first-line metastatic uveal melanoma. Daren, please take it away. Thank you, Yujiro. Before we go directly into the trial design, what I'd like to do is make a few comments to set the stage for why we're so confident going into this study and what you're going to hear from our key opinion leaders today. These are investigators who really lead the field in clinical research with respect to uveal melanoma. From a high level perspective, what you're going to hear today is in the metastatic uveal melanoma setting, the treatment with the Darovasertib/Crizotinib combination produces an unprecedented overall response rate in patients with both treatment naive as well as relapse disease. Further, the progression-free survival you'll see today is more than double than what's been recorded previously with standard of care agents. This is all delivered with a manageable safety profile with a low rate of discontinuations due to adverse events. Layered on top of that is what we've seen in the primary uveal melanoma setting, which is an impressive rate of tumor shrinkage in subjects treated with neoadjuvant, either Darovasertib or the combination, including Crizotinib. For the first time, you're gonna see evidence of a patient who had a large uveal melanoma tumor, who not only was able to save his eye from the treatment, but also was able to preserve his vision. That sort of sets the stage for the registration trial, which is shown schematically here. Essentially, you're all aware that we had a discussion with the FDA at the end of March, mainly to discuss the trial design and key endpoints. This discussion really anchored on two key guidances. The first was Project FrontRunner. Of course, that's a guidance that's designed to bring exciting new therapies into earlier lines of treatment, which is very applicable here because we're talking about the treatment-naive setting. Also, there's the guidance around Accelerated Approval. Again, the idea here would be to get exciting therapies to patients with significant unmet medical need. I don't think anyone can argue that metastatic uveal melanoma doesn't have great unmet need. It certainly does. The trial design shown here is very similar to what we've described to you in the past. It's not very different. The subject population remains patients with metastatic uveal melanoma who are HLA-A2 negative. The treatment arms are either the Darovasertib Crizotinib combination in the treatment arm versus the control arm, which is a choice of either checkpoint inhibitor therapy, which can come in the form of single agent checkpoint inhibitors or the combination of ipilimumab and nivolumab. For those patients who have a contraindication to immunotherapy, chemotherapy, such as dacarbazine, can be chosen. The randomization is in a two to one fashion. The design is a seamless phase ll/lll type design, where approximately 230 patients will be enrolled in the phase ll component. Additional 120 patients will be enrolled to complete the phase lll. In the phase ll portion, there'll be a small cohort of subjects that will be part of the dose optimization. Basically, in this seamless design, this nested group of patients will actually be included in the registration portion of the study. As the go-forward dose is chosen, patients will be continued to be enrolled towards the first co-primary endpoint of median progression-free survival. This will allow the potential for Accelerated Approval. Upon success at this first milestone, patients will continue to enroll to complete enrollment for the second co-primary endpoint of median overall survival to allow full approval of the combination. I would just remind people that, you know, this combination of Darovasertib and Crizotinib has Fast Track designation. It's our hope with this designation it'll allow us to continue the dialogue with the FDA in a seamless way throughout the conduct of this study to allow us to rapidly get this combination to patients. With that, this lays out the trial design with a few words about why we're so confident going into this study. Now it's time to really hear the details from the experts who treat patients with this disease. Now I'll hand it off to Dr. McKean from the Sarah Cannon Research Institute. Dr. McKean. Great. Thank you so much. I'm excited to be here to present this data today. Today we're disclosing the Interim Analysis of the first 63 patients treated with Darovasertib Crizotinib at the expansion dose. You can see here the patient profile, the patients treated on study, in addition to the patients treated on the frontline Tebentafusp study. You can see that the patient population treated on study has had a predominance of poor prognostic markers. You can see the elevated LDH, which can indicate disease burden. The percentage of patients with a lesion measuring greater than three centimeters has been 66% in any line, in addition to 60% in the frontline setting. Patients have had a predominance of hepatic and extrahepatic disease. When you compare the frontline patients to the frontline Tebentafusp patients, you can see here that the elevated LDH was seen in 50% vs. 36% on the Tebentafusp study. More patients with lesions greater than three centimeters compared to only 45% of patients on the frontline Tebentafusp study. Additionally, more patients with hepatic and extrahepatic lesions, 50% versus 44%, in the Tebentafusp study. Next slide. Starting out with looking at the AE profile. You can see here that the combination of Darovasertib and Crizotinib has been very manageable. On the left, you see the summary indicating that no grade four events have been reported. One grade five that was felt most likely related to disease. Importantly, the SAE rate was 9% and only 6% of patients discontinued study drug due to AEs, which is really indicating that the side effects were very manageable, with, you know, supportive medications. You can see the summary on the right that most of the side effects were GI toxicities, diarrhea, nausea, vomiting. Again, predominantly grade one and grade two that were easily managed. Other side effects there, edema, fatigue and rash. Next slide. Moving on to efficacy. Just excited to share here, you know, very exciting frontline metastatic uveal melanoma clinical efficacy. You can see here in the waterfall plot that in the 20 patients in frontline metastatic uveal melanoma treated on the phase ll Darovasertib and Crizotinib expansion arm, all but one patient had tumor shrinkage. There was a confirmed overall response rate of 45% indicated with the plus sign below the patients with confirmed response. There was tumor shrinkage demonstrated in 95% of patients. This has really just been very exciting to see. This efficacy supports a registrational strategy in the frontline setting. Next slide. Looking at any line metastatic uveal melanoma patients, you can continue to see just a dramatic waterfall plot here with predominance of patients having tumor shrinkage and a number of patients achieving partial response. The entire population of any line metastatic uveal melanoma patients treated, you can see here with a 30% overall response rate and an 87% disease control rate. 92% of patients had tumor shrinkage. This clinical efficacy was seen in any line metastatic uveal melanoma irrespective of HLA-A*02 status and in both hepatic and extrahepatic metastases. You can see here the light blue were the first line patients and the previously treated patients are the dark blue in this waterfall plot. Next slide. When we look at hepatic only. For metastatic uveal melanoma patients, the primary place of metastasis, the most common location that you see is in the liver, which is generally it makes it so difficult to try to develop effective therapies for these patients. In the hepatic-only cohort, the 20 patients demonstrated here had a 35% overall response rate and 100% disease control. Every patient had tumor shrinkage treated with this combination. Next slide. Moving on to two patient examples. You know, this is just very consistent with the responses that we've seen in the patient profiles on study. The first patient on the left, this was a frontline metastatic uveal melanoma patient. This was a 40-plus-year-old patient. This was an HLA-A*02 positive patient that had metastasized after about 6 years from their initial diagnosis. This patient had large bulky tumors, as you can see in the picture on the left, in the liver and pelvis. This patient had an elevated LDH of 800, and after starting on treatment, the LDH normalized within 1 month. You can see here, these large tumors have reduced by 49%. This patient remains on treatment for over 15 months. On the right, you see another example of a frontline patient treated on study. This was another 40+ year-old patient. This was an HLA-A*02 negative patient that metastasized after about a year. This patient had many smaller liver lesions. This patient was able to achieve a maximal target lesion reduction of 65%. This patient also continues to have an ongoing response and remains on treatment at 10 months. Next slide. Moving on to PFS data. Exciting to share this swimmer plot here. The last time this data was presented in September, the median PFS was about five months. Now, with additional follow-up, we're seeing a median PFS of about seven months. When you look at that 20-patient hepatic-only subset, the median PFS is now about 11 months. This is just really unprecedented in the field and very exciting for our patients. Next slide. Looking at other clinical trials and assessments of therapy, therapies for patients in metastatic uveal melanoma, you can see here how Darovasertib and Crizotinib compares to other targeted therapies and immune therapies. Looking at the AE profile, seeing here on the left, grade three or greater drug-related AEs, 33% Darovasertib and Crizotinib. This is compared to nearly 50% or greater with any other regimen that's been assessed. You can see 46% for Tebentafusp, 58% for Ipi-Nivo. When you look then at the efficacy and the percentage of patients with tumor shrinkage, looking at, you know, 92% with Darovasertib and Crizotinib compared to ranges between 23% with Cabozantinib. Really no patients with Crizotinib monotherapy having a response or tumor shrinkage, and then ranges between 27%-44% with the other therapies. Looking at overall response rate. Darovasertib, Crizotinib, we're seeing for first line, 45%, 30% for any line. When you look at the c-Met targeting agents, so Cabozantinib, Crizotinib, 0%. There are no responses in patients. When you look at the combination of a targeted therapy with Chemotherapy, so Selumetinib and DTIC, 3% response rate. When you look at Ipilimumab and Nivolumab, a common combination used in the clinic, the overall response rate was 11.5%, and that was not confirmed on study, non-confirmed response. Tebentafusp was 4.7%. We're just really seeing, like I said, an unprecedented efficacy signal and a very tolerable safety profile. The data thus far looking at the median PFS, as discussed that we're now seeing about 7-month PFS for the combination of Darovasertib and Crizotinib. Really seeing between two to three months with any other regimen assessed. Next slide. When we look a little bit closer at the combination of ipi-nivo and compare the frontline patients between the patients treated with Darovasertib and Crizotinib versus ipi-nivo, you can see that we're really seeing a safer safety profile and a higher efficacy with this combination. With ipi-nivo, like I said, the overall response rate 11.5%. The confirmation was not required on this study, compared to 45% with Darovasertib and Crizotinib. The median PFS, about three months compared to about seven months at this time. This was taking into account just a patient population treated on Darovasertib and Crizotinib with a higher poor prognostic features, a higher risk disease population with a higher% of patients having an elevated LDH. Importantly, looking at the safety profile, an SAE rate of 9% with Darovasertib/Crizotinib, compared to 58% for patients treated on the Ipi-Nivo phase ll. Thank you. Next slide. Great. Thank you so much, Dr. McKean, for that terrific walkthrough for the data and obviously, all your key involvement as an investigator on that study. Also, one of our key objectives for the data update that Dr. McKean just walked through, our public investors and Analysts also now have a very good understanding of the clinical data that the FDA observed while we had the discussion in March as it relates to getting endorsement on the first line Accelerated Approval trial design. For our next section on the Darovasertib clinical data update and neoadjuvant uveal melanoma, it gives me great pleasure to introduce Professor Anthony Joshua, the Head of the Department of Medical Oncology at the Kinghorn Cancer Center in Sydney, Australia, who is also the lead investigator on our ongoing IST. With that, Professor Joshua, please take it away. Thank you very much. Thank you very much for having me. I'm very excited to discuss this concept of neoadjuvant/adjuvant Darovasertib in primary uveal melanoma and to demonstrate and discuss the paradigm that we're developing here. As you can see in this slide, this is a phase ll study which is currently being developed. In this phase ll study, the patients will get both neoadjuvant therapy as well as adjuvant therapy. The first cohort will be patients who have an a priori destination of unfortunately having a enucleation as determined by the treating ophthalmologist. The second cohort will be those who had a determination for brachytherapy. They will both be treated with single-agent Darovasertib for, to maximum benefit up to six months before the primary local therapy is undertaken, be that surgery in the enucleation cohort or brachytherapy. The primary endpoint will sort of apply at that point, being both a safety in cohort one, eye preservation, to see how many eyes can avoid enucleation. In cohort two, a decrease in the radiation dose from the brachytherapy, which may have long-term visual consequences. That will then be followed by a period of adjuvant therapy with treatment with single-agent Darovasertib for six months and then for routine follow-up to prevent what is really the devastating consequence of uveal melanoma, that is the development of metastases. We haven't really had any proven adjuvant therapies in the clinic to date that have come with such rationale as Darovasertib. We're all very excited about the potential for this drug, not only to save eyes and save vision, but also to decrease the rate of metastases subsequently. The trial will, as mentioned, cover those primary endpoints, but also the secondary endpoints being useful vision at 1 year. As mentioned, what I'm particularly enthusiastic about is relapse-free survival, both at 1 year and at a 3-year time point, bearing in mind that most of the metastases occur at the 2-year time point. Certainly we'll have enough time to understand the impact of the adjuvant component. This trial, this phase ll trial, will have, in one study design, three important questions will be asked. One will be the ability to save the eyes by shrinking the tumor in situ, allowing the eye to avoid enucleation. The other being a brachytherapy cohort, allowing decreased dose and finally adjuvant therapy to save lives. A very exciting protocol, which is gonna be taken globally, targeting Q2 2023. Next slide. The rationale for this study design has really come from the experience, both my own and that of my colleague, Professor Shackleton, in treating patients on our ongoing IST with neoadjuvant Darovasertib. You can see here that there are two cohorts presented here which form the preliminary rationale for the phase ll study. The first is our ongoing study, patients who were destined for enucleation. In that study, you can see here the tumor responses to date. Along the top, you can see how long the patients were treated for in that N equals 6 cohort trial still enrolling. In the first, three patients, they were required to stop treatment at 1 month as a safety measure to ensure there are no perioperative complications, which there were not. Subsequently, the protocol has now been expanded to allow treatment up to a maximum of 6 months. Similar to the soon to be started phase ll study. You can see here the excellent responses we've had to date in that study, and the case study that Professor Shackleton will present shortly. There is also a small number of patients who've been treated with metastatic disease, who've had their ocular primaries in situ, and you can see the best ocular responses as outlined on the right of that slide, with tumor shrinkages ranging between 15 to near 100%. Next slide, please. Here you can see very clearly, some of the shrinkages seen both by ocular ultrasound and by direct fundoscopy. The first slide there on the far left, a 22% shrinkage after only 1 month of therapy. Again, unprecedented really in the field. We haven't really had any agents that can shrink tumors in situ and be tolerable and allow eyeballs to be saved. Going into the middle slide, we had a very nice 31% shrinkage, after 1 month. You can see those pictures there with the tumor shrinking from 12.48 mm down to 6.9 mm after only one month. In the final picture on the far right, very clearly visible in the bottom of that eye is this tumor, which is close to obstructing the optic disc and fovea. You can see how nicely that shrinks away at month 2, and those vascular arcades being now visible on the back of the retina. Certainly, very nice data to date and forms an excellent both preclinical and now clinical rationale for a neoadjuvant and adjuvant paradigm to be developed with Darovasertib in uveal melanoma. Next slide. Great. Thank you so much, Professor Joshua, for that terrific walk through on the neoadjuvant uveal melanoma. Thank you also for your continued partnership with IDEAYA on the IST. I know the organization's extremely grateful for all your contributions to this study, and we're very excited to see how the data continues to mature with more follow-up and more patients. Next, we're delighted to have Professor Mark Shackleton, the director of oncology at Alfred Health, Melbourne, Australia, provide a case study walk through of his neoadjuvant uveal melanoma patient, which we believe is the first reported case of a patient spared enucleation through a systemic therapy. I know Professor Shackleton, we caught up a few days ago. Personally just at least I thought this was one of the most inspiring stories that I've heard in my career on a benefit a patient received with therapy. With that, it really just gives me a really pleasure to introduce you to walk through your patient here. Thanks very much, Yujiro. It really is a great privilege to present this case, which is, you're right, it's really one of the most remarkable and satisfying cases I've been associated with in my career, I will say. It's certainly been a great opportunity to be partnering with Anthony, and with your company, in the development of this combination, which I really genuinely believe is gonna save eyes and save lives, with ongoing clinical development, given the nature of the data that we've seen so far, which is really quite something. To kind of put a human face, I guess, on the story, I'll talk about a patient of mine that I met just before Christmas time 2022. He's a 70-year-old man. He's actually already blind in the left eye, as a consequence of many years of history of smoking and peripheral vascular disease, and a previous diagnosis of a left retinal artery infarct. That is a blockage of one of the blood vessels in the left eye, which left him permanently and irreversibly blind on that side. He was otherwise really quite well. He had the typical sort of medications that peripheral vascular disease patients are often on, a statin, an antihypertensive, and some low-dose aspirin, but generally a very, very high functioning man living with his family, grandchildren, et cetera, et cetera. He presented in about October, November, with really rapidly declining vision in his right eye, and therefore overall rapidly declining vision. He was referred to one of my ophthalmological colleagues for evaluation. The ophthalmologist immediately identified a very large uveal melanoma in his right eye, dominantly obstructing vision. This is a really big tumor, 16.5 millimeters in its maximal height and 18 millimeters in its maximal basal diameter. It was further compromising vision as a consequence of severe cataract that it was also causing. My colleague at our eye and ear hospital here in Melbourne called me up and said, "Is there any way you can try one of your clever drugs to see if we can save this guy's eye? Otherwise the only treatment for this tumor, which gives him any hope of cure, is to completely remove the eye, which would render him permanently blind in both eyes. I reached out to the team at IDEAYA and was really excited to get their support to treat this patient with combination Darovasertib and Crizotinib. With the goal being to avoid enucleation and therefore preserve vision in this patient. Really the response has been striking. At every month of review, he's exhibited impressive, obvious tumor shrinkage. He has regular ophthalmological examinations once a month, in addition to seeing me once every two to four weeks for treatment prescriptions and management of monitoring of toxicity. He's currently on the fourth, I think now it's actually the fifth month of treatment, and remains on therapy, doing very well. He's overall tolerated treatment very well. The main side effect he's had has just been at a grade one to two diarrhea, which we not uncommonly see with this combination, managed with simple antidiarrheals. He now doesn't need an enucleation. Next slide. As I said, the tumor's been monitored every month, by the team at the Eye and Ear Hospital, and really quite strikingly, only after the first month of treatment, the tumor had already shrunk down by about 30%. Even at that stage, potentially being treatable with the placement of plaque-based radiotherapy rather than needing enucleation. The response was really very rapid and quite dramatic and actually even more remarkable because I had to stop treatment for a couple of weeks over the Christmas period when he incidentally developed COVID and had some abnormal liver function tests associated with that. I just had to shut off his targeted therapy. He recovered from COVID. He's settled down. His liver function tests are now fine. Then he was put back onto targeted therapy and really has had no major side effects that can be attributable to the combination apart from the diarrhea. Every month that this guy gets examined, his tumor just shrinks down and down and down. The response has been so impressive that he's now planned to have plaque-based treatment. Really the ophthalmologists are keen for me to just to keep treating him, to see just how small we can get this thing. The idea being that the smaller it gets, the smaller the radiation dose that the retina of the eye is likely to be exposed to offer curative intent radiotherapy treatment. He's actually gone on to have the cataract treated, with an intraocular lens replacement, and now has excellent vision in that eye. I mean, before he, before we started, he was really, he was, you know, more than legally blind with pretreatment vision score of six on 120. His post-treatment score after the cataract was replaced, is now six on five, which is probably better than my eyesight. He remains on treatment doing really well. The ultrasound examination shows really quite dramatic changes that you can see there on the right-hand side. The baseline image showed this really huge tumor causing substantial impingement of impairment of vision. You can see that that tumor is really on the repeat ultrasound 4 months later, you know, substantially reduced by about 80% overall. It's a really an incredible response. Next slide. This is just a funduscopic demonstration of that with the pretreatment funduscopic image on the left-hand side showing an obvious left tumor in that sort of right upper quadrant there of the fundus. The most recent funduscopic image taken a month or so ago shows that that tumor is, you know, clearly and obviously substantially diminished, consistent with the overall improvement of his vision. Yeah. Thanks for the opportunity to talk about that case. As I said, it really is one of the most remarkable and satisfying cases that I've been associated with. You know, thanks to this therapy, this guy can now see and is likely to do so for a long time. Well, thank you so much for that walkthrough, Professor Shackleton. Yeah, I think, you know, when you, when you see this image, it's yeah, really, you know, pictures definitely can say a thousand words. I know for the team here, and I know when we saw this image it was yeah, just really was made a big impact, I know for us as well. Thank you so much for the opportunity to, you know, for everyone to hear the patient walkthrough today. I'm gonna go ahead now and just proceed with the closing remarks section of the presentation today. Today marks an important day in IDEAYA's corporate history as we achieve several major milestones for our lead clinical program, including an FDA-guided Accelerated Approval trial design in first-line metastatic uveal melanoma and a broad clinical efficacy update in both first line MUM and in neoadjuvant uveal melanoma. Today, we believe we have demonstrated that Darovasertib has the potential to be an important treatment for metastatic uveal melanoma with a compelling reported confirmed overall response rate by RECIST, disease control rate, meaning progression-free survival, including in the first-line metastatic setting. We continue to see highly encouraging clinical efficacy from Darovasertib in the neoadjuvant uveal melanoma setting, including a partial response from monotherapy in only one month of treatment. In our first reported case of a systemic treatment sparing a patient of enucleation. This slide provides a summary of our broader clinical and commercial strategy for Darovasertib in uveal melanoma. Based on Darovasertib's unique mechanism of action, oral delivery, manageable AE profile, and clear demonstrated ability to consistently shrink both primary and metastatic uveal melanoma tumors. We believe this agent has broad applicability across the patient journey, including in the neoadjuvant, adjuvant, and first-line metastatic settings. Lastly, due to the high unmet medical need in both the primary and metastatic setting of uveal melanoma, we believe there are multiple first-line Accelerated Approval opportunities, which is unique for a solid tumor indication. We believe Darovasertib is an ideal lead clinical program for IDEAYA, based on the compelling clinical efficacy and manageable safety profile observed in a high unmet medical need indication, and the opportunity this program provides to pursue multiple first-line Accelerated Approval opportunities along the patient journey. In addition, as the treatment of uveal melanoma in the U.S., Australia, and Europe occurs primarily in specialized treatment centers, it creates a tractable commercial opportunity for a biotechnology company such as IDEAYA. Darovasertib is followed by an emerging clinical and pre-clinical pipeline of potential first-in-class precision medicine oncology programs targeting large solid tumor populations that will enable IDEAYA to build a world-class organization and diversified clinical pipeline. This exciting first-in-class pipeline includes MAT2A inhibitor IDE397 in phase ll, targeting MTAP deletion lung, gastric, and bladder cancer. PARP inhibitor IDE161 in phase 1, targeting HRD breast and ovarian cancer. Pre-clinical stage Pol-theta helicase and Werner helicase programs, many of which were highlighted at this year's AACR. This now completes our prepared remarks. Operator, you may now open the line for the Analyst Q&A portion of our webcast. Thank you, Juro. At this time, we'll begin conducting our Q&A session. As a reminder, if you'd like to join the queue, please raise your hand to indicate that you have a question. With that, our first question comes from Anupam Rama at JP Morgan. Anupam, can you hear us? Yeah, we can't hear you, Anupam. Can you hear me? Yep, we can hear you now. Oh. Sorry about that. No worries. Two quick questions from me. One for the company and one for the KOLs on the line. For the company, just based on the totality of the data that you have to date, for the phase ll/lll frontline MUM study, what's that power to show on PFS, and what are you assuming that investigators' choice shows? For the KOLs, know that phase ll/lll front is being studied in frontline MUM, but if available, would you consider using the Daro criz combination in your more refractory prevalent population, given the all-comers data that we've seen to date? Thanks so much. Sure. Thanks, Anupam, and appreciate the question. Dr. McKean, do you wanna maybe first start with just answering the question on the pre-treated MUM and Darovasertib/Crizotinib combo? Sure, absolutely. I mean, I think, I think there would definitely be excitement to, you know, obviously, I think what we're demonstrating is trying to have as many opportunities and settings to try to use this treatment as possible. I mean, I think there's gonna be a lot of excitement for the frontline setting, and trying to treat patients as soon as possible with this combination. Yes, there's definitely excitement in the treatment-refractory setting as well. Great. Thank you, Dr. McKean. Daren, do you wanna take the question on the powering on the PFS? I know we haven't specifically noted the powering, but. Yeah. Work backwards to get all the numbers. Yeah. Without getting into tremendous details, I mean, you're looking at the Tevi study where the control arm had a 16-month median overall survival. You looked at the graphic that was shown today about what standard of care delivers in terms of median progression-free survival of around 3 months. Those are good sort of starting points for us to look at. The trial was designed around those types of metrics. You know, we have designed the study with the FDA in such a way that we can show superiority to compare to numbers like that. Thanks so much for taking the question, and congrats again. Yep, thank you. Next question, operator. Thank you for the questions. The next question comes from Maury Raycroft at Jefferies. Hi, everyone. I'll add my congrats, and thanks for taking my question. Wondering, just based on the clinical experience so far, can you talk about enrollment expectations and timelines for the registrational study? For picking or confirming the go-forward dose, how long do you think you will need to do that, and will you do an interim analysis around that decision? Sure. I'll start and then I'll pass it to Darren. In terms of the enrollment cadence, Maury, you know, we've to date, have enrolled very quickly. Even with a limited number of sites in the U.S., you know, roughly 10 sites, we've been able to enroll at even, you know, 15 patients a month. The registrational study will be a much broader effort in the U.S. as well as globally, including across Europe. You know, we'll give an update on that, we anticipate as we get, you know, this launch, that's been our historical experience. In terms of the other questions there, maybe Darren, do you wanna comment? Just a few things. One is the fact that we're including the ipilimumab and nivolumab combination in the control arm obviously ought to help enrollment as well. It's a very commonly used regimen in the U.S., so that's the first thing in towards rapid enrollment, and we're excited about that. Not only that, we're excited about the opportunity of just showing once and for all if this combination is the king in the UVM melanoma space. This will be one of those studies that allow us to make that claim because there'll be no other treatments that people can point at. That's the first thing. The second thing, with respect to the dose optimization, what's so beautiful about the design that we have is it's a seamless design that allows us to look at two cohorts of patients. I have to say that based on the dataset that we have, not only from single-agent Darovasertib, but the combination of Darovasertib with Crizotinib at Darovasertib doses from anywhere from 100-300 milligrams. We're fairly convinced that the 300 milligram, 200 milligram dose combination is the go forward dose. We acknowledge that the sample size is not large, we want to, you know, bolster that with a larger N. In part of the registration trial, the 300, 200 dose will be compared to the 200 dose in a seamless way while the control arm is continuing to enroll. Using a pick the winner type design, we'll go forward with the optimal dose, and we'll do so in a way that really shouldn't, you know, really afford much of an effect on the timeline whatsoever. It is embedded within the registration portion of the study, which is what's so great about this and then, of course, you know, we have the phase ll tied into the phase lll in a seamless way as well. It's really a nifty design, and the FDA was very supportive of what we proposed. Great. Thanks. Thank you, Darren. Any other questions? Got a quick one. Yeah. Yeah. One other question I was gonna ask if I might, for the hepatic-only strategy, if you can talk about that and if you can stratify for this population in your registrational study and how this could factor in commercially, maybe considering competition and, with or without NCCN guidelines or compendia listing updates. Sure. I'll take the commercial piece, Darren, if you wanna take the first part. Well, you know, listen, I think the reason why we kind of highlighted the hepatic only patient population is for two reasons. Number one is, you know, obviously if you don't have disease beyond the liver, perhaps your disease isn't as advanced as, you know, patients that have metastases in multiple organs. Remember, you know, when you're comparing our results across the board to other therapies, Ipi-Nivo, single agent checkpoint inhibitors, the TEBI study, what frequently happens is in these trials for just by chance perhaps, the patient populations in those studies tend to have lower LDH, lower tumor burden as Dr. McKean pointed out, these patient populations aren't as heavily burdened with disease and therefore, not only is the data that we're showing today, you know, quite impressive, but if you think about it in the context of we're not really comparing apples to apples. In fact, what we're comparing it to with other therapies is a patient population that perhaps would be doing better in any case, and yet there's still a dramatic difference. That's one thing to keep a note. By looking at these patients with hepatic-only disease, if you think about them as sort of a surrogate for maybe perhaps patients whose disease isn't quite as advanced, again, you see a very, very impressive median progression-free survival of 11 months, which may bode well for us in the registration trial. If we have a patient population like we saw in the TEBI study, our results may be even more remarkable. The second part of this is, you know, there's a lot of, you know, talk around the liver-directed therapies. They're used very frequently, of course. What our data shows that, you know, compared to, you know, the liver-directed therapies that are reported, you know, the progression-free survival in that patient population for the treatment of Darovasertib and Crizotinib, you know, clearly, you know, looks, you know, very, very nice relative to what a liver-directed therapy can provide in terms of progression-free survival. Those were the sort of the impetus to show the data, but in terms of the registration trial, there'll be no really emphasis on selecting out that patient population because we feel like we can help all patients, irrespective if they have disease beyond the liver or not. Does that answer your question, I hope? Yep. Yeah. It's very helpful. Thanks for that, Darren. Maybe just to add on the commercial piece, Maury. You know, as you know, you know, our perspective here is, you know, we'll be pursuing first line Accelerated Approval in HLA-A2 negative, and at least we anticipate that we have the opportunity to be the first potential approval there. But as you know, we're not forgetting about the HLA-A2 positive, based on our data. We, we see activity irrespective of HLA status. And I think the hepatic-only is potentially could be a really nice opportunity there when you think about A2 positive. As we know, there's a drug approved there. You know, we're basically at a point here if that data continues, where PFS is, you know, approaching a year, right? It's a situation where the PFS is, you know, basically exceeding historical median OS, which is, you know, quite a remarkable result in metastatic uveal melanoma. We also know in the first line setting, if you look at the TEBI data, both the treatment arm, the comparator arm, our study, that about 50% of the patients have hepatic-only disease. You could imagine even in the HLA-A2 positive, you know, as we noted around our Compendia strategy, if you're making a decision with our agent versus another, and if that type of PFS continues, you know, I think that's a, you know, will be quite attractive. I think that's how we're thinking about it, Maury, from a commercial perspective and also how the value of that hepatic-only could continue as we continue to advance this program. Makes sense. Congrats again. Thanks for taking my questions. Sure. Next question. Thank you. Great. The next question comes from Ashik Mubarak at Citibank. Hi, team. This is Ashik on for Yigal Nochomovitz at Citi. Thanks very much for taking my questions. Really great to see this data. Congratulations. I wanted to ask a couple on neoadjuvant, starting with, I think the case study that you shared was very compelling. I'm just wondering, for the neoadjuvant setting, the IST data you shared, it looked like some of the best responders came with a combination of Darovasertib and Crizotinib. It looks like your company-sponsored study that you're getting up and running will be with the monotherapy. I'm wondering if you can kinda comment and remind us on why you're going forward with the monotherapy strategy and what you think Crizotinib may or may not add in the neoadjuvant or primary uveal melanoma setting. Sure. I think that the first part of that, Ashik, is really around the mechanistic rationale, which I covered in the beginning of the presentation, in terms of the MOA. With that, Mike, if you're on, Michael White, our Chief Scientific Officer, maybe Mike, you could answer that one. Yeah. Thanks for that question. Clearly in the primary setting, as Yujiro noted, the genetics really defines the mechanism of action. We have no evidence that we require a MET receptor inhibitor in that setting. The monotherapy is working great preclinically. The MOA is very consistent with what our investigators are seeing clinically, and that's usually the case when you get your MOA correct. The MET receptor is coming into play in the metastatic setting because of that bypass mechanism. That's where we think it's important to have the combination. Yeah. I think just last piece, Ashik, I'll just mention it. Yeah, I think our view is we just, you know, we just need additional treatment duration on mono. You know, as you saw, we already had, you know, an early PR at 1 month. We also have in the metastatic setting, you know, in a half a month, by PET, you know, well over what is a 60% tumor reduction. Others, you know, we're already at 20% in that one to two month range. That other patient again was at month 4. Got it. That's very helpful and very clear. Sure. Let me ask one more then on potential duration of treatment within the neoadjuvant setting. It looks like the design is set up for 6 months neoadjuvant followed by 6 months adjuvant. Does that? Is there potential for patients to be treated beyond that period in a more maintenance-like setting, or is that not part of the potential regimen? Yeah, that Daren, do you wanna take that? Yeah. I would say that that's a really great point, that's something that we've been discussing. I mean, just like with the the Darovasertib in the neoadjuvant setting, we as a single agent, we have to start somewhere, right? The place to start is monotherapy Darovasertib, you know, presumably it's by itself is really well, well-tolerated, that's when you start thinking about how long can I give this treatment. The original study is designed to do a 6 months neoadjuvant portion with definitive local therapy, followed by 6 months in the adjuvant setting. Suffice it to say that we're thinking hard about that, especially as, you know, was pointed out by our key opinion leaders here on the call today. I mean, you know, metastasis is the biggest problem. It can happen several years down the road. You have to ask yourself, you know, why do I wanna stop? If I know a patient has a 50% chance of metastasis, why do I wanna stop the therapy at all in the adjuvant setting if it's well-tolerated? I think those are great questions for us to ask, and that's what we're asking ourselves now. I think we need to have a data set to begin with. That's where we're starting, but that's probably not where we're gonna end. We haven't decided exactly, you know, at what point and how exactly we're gonna do that. Suffice it to say, it wouldn't be crazy to think that there wouldn't be a longer duration of therapy at some point down the road, but we just aren't ready to cross that. We wanna build some data to make some decisions on. Got it. That's super helpful. I think just the only other piece I would add there is, we know that Darovasertib monotherapy can be tolerated for a very long period of time. You know, going back maybe some time in history here, but from our phase I Darovasertib monotherapy, we had a confirmed complete response. Actually, a patient in Paris that was on therapy for over five years as a monotherapy, you know, completely tolerated throughout that whole period. We had also a whole nother set of patients that were confirmed PRs that remained on therapy for over two and a half years. All those patients as well, you know, were able to have long-term tolerability. We do know from that perspective, from at least from an AE perspective, the possibility is also there. Got it. This is, this is fantastic. Thanks again. Sure. Yeah. Thank you. The next question comes from Charles Zhu at Guggenheim. Hey. Good morning, everyone. Thanks for taking the question. Congratulations again on the strong updates across the board. Maybe my first one, going back now to the metastatic setting. On the swim lanes, there were a handful of patients who were being treated beyond progressive disease. Can you talk about some of those mechanics and how real-world duration of therapy may ultimately compare to a numerical progression-free survival? Thanks. Yeah, I mean, I think if you look at that swimmer plot, you know, I think folks could look at it and sort of determine that. You know, our clinical experience is that, you know, patients are continuing to get treated beyond progression. In some cases, it's been, you know, six months or more, some it's been a bit less. If you sort of eyeball it, you know, we think it's roughly about three months beyond progression. We know with Tebentafusp, patients are also getting treated beyond progression for quite a long period of time. Charles, I think at this point, that's sort of a rough estimation. At least practice to date, what we've seen in the trial, our patients are getting treated beyond progression, roughly in that range of about three months. Great. Then maybe my second question now onto the primary uveal melanoma setting. Not sure if I missed this one, but I was wondering if you could clarify one thing. Just given the strength of your data so far, as well as the amount of safety data you have from the metastatic setting, could your phase ll neoadjuvant study support re-registration? If not, how much additional data from that study would you need before you approach the FDA for guidance on re-registrational development? Thanks. Sure. Darren, you wanna take that? Yeah. I mean, you know, in that study, we have 40 patients in each arm. I think as the data accrues, I think we can have discussions with the FDA. You know, there are things that they may want to see as part of the evaluation process, in order to make the study registration enabled. It's hard to have those discussions with the FDA without any data. I think our first objective is to get, you know, those first 10, 20 patients in, start seeing the kind of information that we're presenting today, start having those discussions on what the key parameters are. Likely there'll be some expansion of what we have in each one of those cohorts, that's to be determined. Again, it depends on the magnitude of effect, right? If we do the first 10 patients and all of them save their we save the eyes in the first 10 patients, that's a different discussion than if you maybe saved one out of 10. You know, it's kind of a work in progress, but we obviously have to have data to have an intelligent discussion with the FDA, that's our first objective. Great. Thanks, and congrats again. Great. Thanks. Thanks. Thanks, Charles. The next question comes from Gregory Renza at RBC. Great. Thanks, Ujira and team. Let me add my congratulations as well on the great updates today. Maybe just a quick one for me, perhaps just circling back on the inclusion of Ipi and Nivo on the comparator arm. Certainly helpful to hear your thoughts on the potential impact on speed. Just wanted to gather your views on how that would impact target ORR, maybe PFS as well as potential powering assumptions. And maybe for the docs, just curious on thoughts on how Ipi/Nivo could perform in HLA-negative patients only, perhaps compared to all comers and HLA positives. Thanks so much. Darren, you wanna take the first part? Yeah, I can take the first part for sure. I mean, in terms of powering the study, it kinda makes things easy because if you look at the progression-free survival of ipi/nivo versus single-agent checkpoint inhibitors, you don't really see too much of a difference. In fact, there are many people that think that there's really no difference in overall survival. In fact, what little data is out there maybe implies that the overall survival might be worse with the ipi/nivo combination, it's clearly more toxic. I think everyone agrees with that. Perhaps the response rate is a little bit higher. In terms of the endpoints that we're using in the registration study, median progression-free survival and median overall survival really didn't have much of an impact, which was the beauty of it. We think that the two regimens are likely equivalent in terms of, what the patient gain is, but clearly there's a difference in toxicity. Great. Dr. McKean, I think the question there was around, you know, activity Ipi-Nivo based on HLA status. I'm not sure I've seen that data before, but I don't know if you've seen something there. No, I haven't seen any data in patients treated with ipi/nivo that's stratified by HLA status. I think, based on mechanism of action, you'd anticipate that there would still be similar activity versus Tebentafusp, where, you know, that's clearly only offered to patients that are HLA-A2 positive. Great. Thank you. Thank you. The next question comes from Matt Biegler at OpCo. Great. Hey, guys. Thanks, thanks for the questions and congrats on the data from us as well. It looks really fantastic. Yujiro, maybe just first, a little bit more on the nested design of the pivotal trial, the decision to look at two doses. I'm assuming that's being done to comply with Project Optimus, but can you confirm? I had a couple of questions for the doctors, either Doctors Joshua or Shackleton. It doesn't look like any patients had been enrolled into the brachy cohort yet. Is that just a function of, like, study startup and, you know, waiting to get comfortable with the treatment? Or is that, you know, more of a broader indication of, I guess, the differences in those two populations? The third question is, I think it's one that the investment community more broadly is wondering is, like, how do we define a threshold for saving the eye? Is that more of a patient or doctor decision, or is there some real and fast, you know, number or reduction that you're looking at? Thanks again. Sure. Maybe Professor Joshua, you wanna start with the neoadjuvant question, and then we'll come back to me. Yeah. The IST, which is currently open, is only designed for patients who have an a priori decision to have an enucleation. It was not designed for the brachytherapy cohort. That's not to say that if a patient who it was a priori thought to need enucleation, the tumor shrunk significantly, that they could then go on to brachytherapy as their primary therapy. They have to initially have that decision that this patient is suitable for enucleation as an entry criteria, and given that was how we wanted to, you know, get histology and understand really how the drug was working inside you. That, there hasn't been any intent to enroll someone who's only meant to have Brachytherapy to date. They have to, as per the inclusion criteria, have a determination they require enucleation. The threshold for enucleation is and plaque therapy in some ways are reasonably precise in the ophthalmological community. I'm speaking a little bit out of my lane here because I'm not an ophthalmologist. The plaques come in certain sizes and shapes and their radiobiological parameters, we know you radiate to a certain depth. Some tumors are just too big for a plaque to cover them to a sterilizing dose. That sort of it defines how you would determine whether someone needs enucleation or needs a plaque. Got it. Yujiro, just a question on the nested design, and is that to comply with Project Optimus? Sure, yeah. I can take that. Daren, if anything additional. I mean, that was our base proposal to the FDA, Matt Biegler. I just wanna make it. You know, for us, that was best case scenario, which is what we were okayed on by the FDA. As you know, for any study like this where you're moving forward into a registrational trial, dose optimization will be required, as we're seeing across the board with the FDA. We have been doing dose optimization for some time, this was our sort of best case scenario proposal. Yeah, this was specifically to help address the FDA's initiative around dose optimization. Daren, anything else here? No, I mean, I'd just add that, you know, good early phase investigators were doing this before there was a Project Optimus. You know, this is what we're supposed to be doing in early phase development, defining what the optimal dose is going forward. We've done that with some preliminary work, and it was agreed that, you know, a larger sample size could be helpful, and that's what we're executing in the registration trial. Don't be shocked if it's the 300, 200, dose going forward, because that's where the data points at this stage. Understood. Thanks again. Great. Next question. Thank you. The next question comes from Zegbeh Jallah at Capital One. Good morning. Just wanted to ask a couple of questions. I think the first, in case I missed it, was just wondering what% of the 20 first-line patients were HLA positive versus HLA negative, and what that efficacy breakdown was? Yeah, Zegba, we haven't broken that down. I think all we can say is that our experience in all of our trial across the board thus far is that the majority of patients are HLA negative, you know, probably in that 60%-65% range and the remainder being HLA positive. In terms of efficacy, we didn't provide that breakout, but what we can say is, you know, dating back to our monotherapy days, all of the combination work we've done to date, we see no difference in efficacy based on the HLA status. That's why we didn't break it out. Perfect. Thank you. The other one is just trying to understand how the decision was made to do a monotherapy versus combo in the investigator-sponsored studies. Kind of clinical question, just out of curiosity. For the tumors in the uvea, is it usually just one big blob or is it multiple small tumors? Just trying to understand it, especially as we think about progression of the target tumor. Yeah. I think on the rationale for the mono for primary Uveal Melanoma, I think we answered that a second ago. Mike White, do you wanna just hit that again here? Oh, sorry. Just to clarify- Yeah. Quickly for the IST, how were the doctors determining which patients to do Crizotinib plus daro on? For example, the case study that was provided, the decision was to use daro plus Crizotinib. How was that decision determined versus just using daro? Yeah. The IST is for monotherapy, Darovasertib. Yeah, I mean, I think. I think what she's getting at, Yujiro, is that, you know, we also have expanded access opportunities for patients, and that's what one of those cases were. It wasn't part of the investigator-sponsored trial. That's kinda how that treatment came about. Got it. Thanks for the clarification. The other one was just trying to understand if we usually get a single blob or is it multiple small tumors as we think about progression? Sure. Professor Shackleton, do you wanna take that? Yes. They're almost invariably blobs. Oh, perfect. You don't get this sort of multifocal type of appearance. They're just usually single tumors. Even in the recurrence setting, it's usually one part of the tumor. For example, it hasn't been quite as well irradiated as the other parts that tend to grow. You don't get like a little piecemeal- pockets of progression, it's usually just one side on the tumor. I think that's really helpful. The last one here is I think you guys have mentioned potentially partnering, daro. I was just wondering now that you're seeing the data, you know, how are you thinking about that? Also thoughts on your ex-U.S. opportunity, 'cause that would also be a partnering opportunity. Yeah. No, I think for us right now for Darovasertib, obviously we're working with Pfizer on the combination with Crizotinib. I mean, our plan here, is to continue independently forward. Yeah, we haven't given any guidance on our goal to partner the program. In Europe as well, I think, you know, there's different models one could use for execution, at least commercial execution there. At least our view right now is, there's a lot of value here, and, you know, more data we generate, more value we're gonna generate for the program. As you can see, especially in the neoadjuvant side, we're, you know, we're really at that cusp of generating what we think is exciting, clinical efficacy data. Perfect. Thanks, guys. Sure. Congrats on the data. Thank you. The next question comes from Zhi-Qiang Shu at Berenberg. Great. Good morning. Thanks very much for taking the question and also congrats on the data update. Very impressive. First question on the metastatic MUM, I was wondering if you can comment on the dose selection portion. What datasets are you looking for in order to select a dose? Obviously, you know, efficacy and safety, but I wonder what specific best case scenario you're looking for. Then regarding that selection, do you need the FDA to sign off on that decision? Yeah, I think we've sort of answered this before, but we'll go through it again. Daren, do you wanna take that? Yeah, just simply stated, the totality of data will come from the data we've approved from single agent Darovasertib, the data that we've accumulated from our phase ll trial at the different doses of Darovasertib, 100, 200 and 300 milligrams. Of course, you'll have a randomized cohort of 300, 200 versus 200 in a registration trial. It'll be the totality of data and its analysis that will determine what the go-forward dose is. Okay. Got it. Then also related to that, in terms of statistics assumptions there, does that dose optimization portion take an alpha from your trial at all? It's a very, very small amount. Let's put it that way. Got it. For the PFS and OS, I recall you mentioned those are two co-primary endpoints. I would assume those have to be hit in order to declare as success. Is that true? Right. The progression-free survival endpoint needs to be hit to move on to overall survival. Okay. Got it. Finally, on the neoadjuvant setting, when should we expect the clarity on the clinical endpoints from timing perspective? I can give you a high level overview of what that is. I mean, you know, think about this. We're really excited about the opportunity in the neoadjuvant setting because some of those time points are on the shorter end. Meaning, you know, if you think about saving the eye, and we're talking about delivering therapy for 6 months and then having an answer. 6 months after your last patient's dosed, you'll know whether in the group of patients you've just treated, have you saved the eye. That, that's an endpoint that presumably, you know, may not take very long and actually could line up with the timing of the registration trial, which was great. In terms of preserving vision, that's another one that's really not so long down the road. If you think about it, you give neoadjuvant therapy, you have your definitive treatment, and then you wait a year, you go ahead and do the visual exam. You know, that's not that far down the road either. These are things that we have to work out with the FDA. We want a body of data that suggests that, you know, we're seeing some improvements in these areas. If so, then to, you know, some of the questions that came before, let's define how many eyes you have to save in order to be clinically relevant and important and think about an Accelerated Approval. How much vision needs to be preserved? What% of patients? How good does it have to get? These are all questions that we have to have a discussion with the FDA about, but of course, you need a data set to begin to have those discussions. Got it. Great. Thanks very much. Congrats again. Thank you. Thank you. I think we have time for one last question, and that will be from Benjamin Burnett at Stifel. Excellent. Thank you so much for squeezing me in. Just real quick, a point of clarification. On the phase ll study design, the PFS statistic that I think you mentioned, is this built around the median PFS statistic and not a PFS hazard ratio? Is that right? Remember, it's about comparing the median progression-free survival between the two arms, right? That usually comes in the form of a hazard ratio that defines success, right? Yeah. Okay. That makes sense. Yeah. If I could come back to just a question about Darovasertib in the adjuvant setting. Like you talked about kind of the duration that one might expect, you know, following treatment like radiation therapy or enucleation. Do you have a sense for under what circumstances patients will be continued on drug? Like, does a patient need to have a response or some benefit in the neoadjuvant setting to then be continued on drug in the adjuvant setting? That's a very good point. I mean, obviously, if a patient's progressing on neoadjuvant therapy, you know, you wonder about the utility. That's why patients will be monitored throughout the neoadjuvant process. We're not saying that everyone's gonna get six months. If the tumor stops regressing after, let's say, two months, it may be time to take them to definitive therapy. Okay. We suspect based on what we've seen so far, I mean, you know, tumors seem to be shrinking in a temporal manner and similar to what Dr. Shackleton mentioned. Obviously, if the patient continues to show benefit, we treat as long up to 6 months for the neoadjuvant setting. Then, of course, post, it's just a matter of presenting those metastases. As I mentioned initially, maybe it's 6 months in the adjuvant setting, but conceivably it could be a lot longer. Got it. As long as there's some sort of tumor shrinkage, if it doesn't meet a certain threshold, but that would define some sort of benefit as being achieved and therefore rationalize use in the adjuvant setting. Okay. Precisely. Okay. Awesome. Thank you very much. Great. Thank you, Ben. Thank you, operator. I think that's the conclusion of the Analyst Q&A portion of the call. I think we can now conclude the Darovasertib update. Again, thank you so much to our KOLs for participating, and thank you so much for our online participants for hearing the update today. Thank you very much. You can now close the line.