Welcome everyone to this morning's webinar. We'll just wait a few more minutes, and we will get started. Or a few more seconds, right? Correct. A few more seconds. Okay. All right. Looks like, it, it's populating pretty well, and most people are in, so we'll go ahead and get started. Good morning, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining us. I know it's been a, a pretty crazy, couple of weeks with earnings and, and, many clinical updates. One of those important clinical updates, was from Zentalis, on Monday, and so we thought it'd be helpful to have the management team from Zentalis here with us, as well as the leading KOL in the space, to discuss the updates and provide additional context. So with that, very pleased to have Kim Blackwell, the CEO, Melissa Epperly, the Chief Financial Officer, and Dr. Joyce Liu, who's the Associate Chief and Director of Clinical Research from the Division of Gynecologic Oncology at Dana-Farber. Before I hand it over to Kim, for those in the audience, please go ahead and email me any questions that you have during the discussion, and I'll do my best to get them asked. The plan today will be to split the discussion into two halves, beginning with PROC and then ending with PSOC. So with that, I'll turn it to Kim to provide an additional introduction to Dr. Liu and an overview of the recent azenosertib monotherapy efficacy and safety update in platinum-resistant ovarian cancer or PROC, and highlight other aspects of the azenosertib clinical development program in ovarian cancer. So, Kim, over to you. Great. Thanks a lot, Tyler, and most of all, thanks for Cowen for hosting the webinar. Before we get started with the discussion, I wanted to make certain we pull up the slides. I also want to thank Joyce for joining us. As you alluded to, she's an associate professor at the Dana-Farber. She's known as a key opinion leader. She's led numerous clinical trials, and most notably for today's call, she was the presenting author on the Zentalis 002 study, which looked at the efficacy and safety of azenosertib in combination with several single-agent chemotherapies. She presented this at this year's ASCO meeting. She also served as the global lead investigator on a very important phase IIb study known as ADAGIO, examining the role of WEE1, the WEE1 inhibitor, adavosertib, in uterine serous carcinoma. So thanks again, Joyce, for joining us. Thank you for having me. Oh, sure. I think I... Yeah, no, no, it's okay. During today's webinar, we just need to make certain the slides are advancing. During today's webinar, we'll be making some forward-looking statements, each of which is subject to risk and uncertainties. I want to start the whole discussion by conveying to you the excitement we have at Zentalis around the potential for azenosertib in ovarian cancer. First, I'll review our very strong and recently updated phase I azenosertib monotherapy data. Next, we'll go over multiple near-term opportunities we have to generate registrational intent data. And then finally, we'll discuss the additional opportunities, which we believe to be blockbuster opportunities, around azenosertib for women facing platinum-sensitive ovarian cancer in the first-line maintenance setting. Along the way, we'll have an opportunity for discussion and question and answers, and certainly for Dr. Liu to help us understand the space a little bit better and the role azenosertib might play in it. Azenosertib has a completely unique mechanism of anticancer activity. It has a completely unique mechanism of action. It dephosphorylates both CDK2 and CDK1, which accelerates DNA damage accumulation in cancer cells, causing them to die. This is important because this mechanism of action makes tumors with high amounts of genomic instability, such as ovarian and uterine serous carcinoma, very sensitive to the anticancer effects of azenosertib. So let's move on to the exciting azenosertib data update from earlier this week. What we showed is we continued to have a robust 37% confirmed response rate, same as what we announced in June. We now have a longer median progression-free survival of 6.5 months, with roughly double the median follow-up of 9.2 months, compared to 4.4 months in June. Importantly... And we need to go back one slide. Importantly, with longer follow-up, we have maintained the favorable safety and tolerability that we announced in June. Let's go on to the next slide. I want to remind everyone of the patient population, which we updated earlier in the week. It consisted of 19 heavily pretreated ovarian and USC patients. We were able to ascertain that since June, eight of the 13 ovarian cancer patients, or 62% of these patients, met the criteria for being secondary platinum refractory, which is a strong indicator of how heavily pretreated these ovarian cancer patients were when they were enrolled in the study. On the next slide is the waterfall of best overall response, demonstrating a continued and very robust 37% confirmed objective response rate. On the following slide is the Kaplan-Meier curve, from which the median Progression-Free Survival of 6.5 months can be determined. This is increased by a month, with longer follow-up since June. Shown here is the swimmer's plot for these 19 patients, broken down by disease type, both ovarian and Uterine Serous Carcinoma, that were included in the analysis. Both ovarian and USC patients had durable and highly meaningful clinical benefit from azenosertib, including those ovarian cancer patients deemed to be platinum refractory and indicated by the Rs to the left-hand side of the swimmer's plot. Let's turn to the safety profile and our update earlier this week. Azenosertib continues to demonstrate an excellent safety profile with additional all tumor type patients enrolled and longer follow-up. In addition, and I think this is a really important point as we move forward in developing the drug, we've seen no cases of febrile neutropenia or safety or sepsis in the safety evaluable population. On the next slide, I really want to finish this section with what we refer to as the tolerability of azenosertib, as indicated by dose reductions, interruptions, and discontinuations. Try to put it in perspective with the other agents that are used or have been studied for use in ovarian cancer. As you can see, azenosertib compares very favorably to the other agents. Most importantly, there have been no treatment-related discontinuations with azenosertib, which is a critical factor for success with an oral agent used as a monotherapy. On the next slide are really the key takeaways from our recent update for azenosertib monotherapy. It's a very active agent in ovarian cancer, and the updated safety and tolerability data provide extremely strong support that not only will azenosertib be successful in clinical trials, but will go on to benefit large numbers of women facing platinum-resistant ovarian cancer. I want to just move quickly to the near-term opportunities we have to get azenosertib to women facing platinum-resistant ovarian cancer. We are continuing to execute on our plan to address the largest possible population of PROC or platinum-resistant ovarian cancer patients with azenosertib monotherapy. Platinum-resistant ovarian cancer, unfortunately, has a terrible unmet need, which you see on this slide. The treatment options at the current time only include single-agent chemotherapy or mirvetuximab, a recently approved ADC, which only about 35% of platinum-resistant patients are eligible for. Azenosertib has demonstrated strong monotherapy clinical activity in this patient population, and we have two ongoing phase II trials, which I will now briefly review. The first of these two trials, DENALI, has a Cohort 2 component of 180 patients, which we anticipate registrational enabling data in the first half of 2025. Cohort 1 of the trial will allow for a preliminary assessment of azenosertib's activity in cyclin E fully characterized patients, and the eligibility criteria is highly similar throughout the trial to the patient population in the recently reported IGNITE study with adavosertib. On the next slide, the second study, MAMMOTH, is a similar patient population to DENALI but requires that patients have progressed on a prior PARP inhibitor. This study is designed to determine the clinical activity of combinations of azenosertib with niraparib versus the activity of azenosertib alone. Cyclin E and HRD status for these patients will be centrally determined, and data from all three cohorts of this study will be available in the second half of 2024. We continue to have a clear plan to make azenosertib available to patients facing platinum-resistant ovarian cancer. We expect to announce the data from MAMMOTH and DENALI in 2024 and 2025. All three azenosertib monotherapy trials in ovarian cancer are well underway. They're finalized in both their design and endpoints, and we are on track to meet the timelines that we've discussed today. DENALI and MAMMOTH have mandatory tissue collection, thus creating several other possible near-term opportunities to understand how Cyclin E positivity relates to azenosertib clinical efficacy. Both of these studies enroll patients similar to the recently reported IGNITE study I just mentioned, showing the substantial and exciting benefits of WEE1 inhibition in platinum-resistant ovarian cancer. So, Joyce, I think I'll stop there, and I would love to hear your thoughts about azenosertib, its safety and activity in platinum-resistant ovarian cancer, maybe some of the work you did with azeno in combination with chemotherapy and, you know, your own personal experience, having treated lots of patients, probably one of the lead investigators for both adavosertib and azenosertib. So I'll turn it over to you for some comments. ... Yeah, thanks so much. You know, I'm super excited about these data. I think that, you know, if we think about all of the advances we've made in platinum-resistant ovarian cancer, and, I mean, there's been evolution in the field, it's still an area of incredibly high unmet need. We need therapies for these patients. We need new agents, and, you know, we need them desperately. These patients have bad disease, they progress, and there's just not enough there. You know, more and more, I think one of the things really exciting in the field is more and more we see that targeting WEE1 really has a role. It's a promising sort of strategy in platinum-resistant ovarian cancer. I think you mentioned the IGNITE data, Kim, and I think that, you know, we've seen that, we've seen other data from adavosertib, and the data that you're showing now, again, really, upholding the hypothesis that we can target WEE1, and these tumors are gonna be vulnerable to targeting the, targeting this as a strategy. One of the things that I'm, I've been really excited about as we've worked a bit with azenosertib and sort of, again, as you've shown in these data here, is the tolerability profile. It's, you know, it's a drug that does not have as much heme tox. And so it's, you know, we can give it on a more consistent schedule. It's really important to be able to give it on a consistent schedule. I think that that's certainly a lesson that we've seen in our experience with the WEE1 inhibitors. You know, not needing to hold the drug, or to have frequent dose reductions, not having dose discontinuations because of toxicity. I think it's really important, and definitely, we've seen that. You know, we've had the combination with chemo here in our center for a while. We enroll to that study a lot because you know, we've seen great activity with it. I think that it's really been a very promising approach, so I'm excited. Maybe I could jump in with just a few questions, Dr. Liu. So with the update on Monday, some investors pointed out that some of the grade 3 heme tox rates went up like a point or two or three, a few points since ASCO. So maybe you could just follow up on your comments on safety with respect to these level of grade 3 heme tox rates relative to what you saw with adavosertib and what the difference is. Yeah, I mean, I think that when you see, like, these changes of, you know, a percentage or a few percentages one way or the other, I actually don't think those are real differences in terms of sort of the data that came from... that we had in June compared to now. I think that's just a reflection. There's a small number of patients overall, sort of, you know, in which we're looking at these data, and it's longer follow-up. And so I don't think those are real differences, that there's a change in sort of the safety profile that was seen in June compared to now. These rates of toxicity that are, you know, that we are seeing with azenosertib are very manageable. And I think that, you know, if you look at the numbers and, you know, the rates of these toxicities, this is not, you know, hugely different than what we manage every day with chemotherapy or otherwise. You know, just felt wise, I think that this is, you know, we definitely find that there—it's easier to manage this drug. It's, you know, it's just the therapeutic windows feels broader than we saw with adavosertib. Okay. And I guess just to double-click on that, so the 9% of grade 3 thrombocytopenia does not concern you at all? You know, I think that it's again, these are patients that you look at the population, and if you look back and, you know, the PARP inhibitors have, you know, a higher rate of grade 3, you know, thrombocytopenia. It's manageable. That's not something that I think is a problem in terms of the drug moving forward. Okay, perfect. I had a client question related to the efficacy. Just, can you comment on the efficacy breakdown between platinum refractory and resistant population? Are you seeing a noticeable difference, or would you expect one population to do much worse than the other? I think that, you know, platinum-resistant and platinum-refractory are tricky terms in ovarian cancer with, with how they can be used, clinically. You know, these patients who have secondary platinum-refractory disease, you know, I think They have acquired platinum resistance. They fall probably bucket-wise, very similarly to patients with platinum-resistant disease. But I think that, again, as sort of was mentioned, Kim mentioned earlier, I think in the context of what we see, in the azenosertib study so far, what it's really saying is this is a heavily pretreated patient population. And these are patients who, unfortunately, once we get out this far in terms of lines, they just don't really respond well to chemo. And so that's again, it's the high unmet need, but I don't think of them as sort of that being necessarily different otherwise. Okay. And if the 6.5-month median PFS holds up in a pivotal PROC trial with azenosertib, how would you use it in your practice? I would be excited to use it. You know, 6.5 months in PROC is fantastic. Okay. Maybe a question for you, Kim and Dr. Liu, maybe you might have a comment. But there's a client question just for the PROC monotherapy strategies with azenosertib that you outlined. Have you guys had regulatory feedback regarding these strategies, or was it largely in consultation with KOLs, and you believe the regulatory pathway is fairly well-defined? It would be helpful just to get additional comments there. Yeah, I'll, I'll take that one, Joyce. So, you know, all of the timelines that we're, we're firmly committed to meeting around the studies we're discussing today in ovarian cancer, have had all the regulatory considerations baked into the timelines that we're presenting, and we're on track to meet the timelines. We do be that the data, in particular from Denali, offers a registrational opportunity. Okay, great. With that, Kim, I'll go ahead and turn it back over to you to discuss the recent strategy update for azenosertib in platinum-sensitive ovarian cancer or PSOC, and then we can take more questions after that. Yeah, that'd be great. This is just going to be a little briefer than the presentation around PROC. So that was a great discussion. I really wanted to kind of finish the formal presentation portion of the webinar with an overview of our plans for moving azenosertib into the platinum-sensitive ovarian cancer setting. On this slide, it really discusses the rationale as to why we have opportunistically adjusted our approach to platinum-sensitive ovarian cancer in order to further increase the probability of our success. We're focusing on PSOC or platinum-sensitive ovarian cancer in the first-line maintenance setting because there are twice as many addressable or treatable patients than in the second-line setting. In addition, more than 40% of these patients are known as HRP or homologous recombination proficient, which is a patient population that typically is considered to be unlikely to receive the benefits of maintenance PARP inhibitor, compared to a different biomarker selected, known as HRD or HRD-positive ovarian cancer. We believe that azenosertib is an ideal drug to move into the maintenance setting because it is oral and it and the adjusted trial design, moving into the first-line maintenance setting, offers the possibility not just for a global registration or approval, but widespread global clinical uptake. The drug will be used in this setting. On the next slide, this slide further kind of outlines the current treatment paradigm for platinum-sensitive ovarian cancer and the large patient population we are seeking to address. The market opportunity is significant, and in a drug that moves into what's shown in the green box, on the bottom of the bottom right-hand side of the slide. Our estimate is that the revenue, five years after launch, would be significantly different between the platinum-sensitive first-line population compared to the second-line population. There is around double the projected revenue in the first-line setting, but more importantly, and most importantly, this is a population of patients, again, shown in the green box, that needs better treatment options above and beyond single agent bevacizumab in the maintenance setting. And our trial is designed—our revised trial is designed to meet this clinical need. On the next slide, sorry, and on the next slide, I just really wanted to give an overview about how we are thinking about the azenosertib opportunity. What we see is an opportunity that encompasses both azenosertib in the platinum-resistant ovarian cancer space and both the platinum-resistant and platinum-sensitive ovarian cancer space. And with the recent adjustment, moving the drug from the second line to the first-line setting, we actually, on this slide, have changed the slide since June to demonstrate that by moving the drug into the first-line setting, we're increasing the number of treatable patients by over 6,000 patients in the first line compared to the second-line setting. On the next slide, I just I really want to come back, and that was a very brief overview, and I'm leaving time for discussions and questions here for the PSOC space. I just want to come back to where we started this discussion, which I, we at Zentalis, are incredibly excited around the opportunity that we have with azenosertib. And I think you can see why. We've shown you very positive azenosertib monotherapy data in ovarian and uterine serous carcinomas. We continue to successfully execute and are on track with our ongoing phase II trials in platinum-resistant ovarian cancer that we believe are generating registrational data. And then we've opportunistically adjusted our trial plans in platinum-sensitive so that we have a large opportunity to help patients and a blockbuster opportunity by moving the drug into the first-line maintenance setting. That's really all I wanted to say. I'm leaving time for questions and answers, and I'll just turn it over to Joyce, because I would love to hear your thoughts about our, you know, adjustments to moving azenosertib into the first-line maintenance setting, kind of the opportunities there, and why azenosertib might be an ideal drug, especially, you know, not only you've discussed it, we've discussed it with a lot of cooperative groups, but I think the audience would really just like to hear your perspective. ... Yeah. So, I mean, I like this adjustment. I think that, you know, when we think about the populations in ovarian cancer that have high unmet need, this, you know, platinum-resistant ovarian cancer we've already talked about is a clearly high unmet need. This is another population that has a really high unmet need in ovarian cancer. These patients who have HRD test negative, HR proficient, however you call them, patients in the frontline setting, they do not have good options in terms of maintenance therapies that work. PARP inhibitors have limited activity as maintenance therapy in this setting. I think that the practice may be moving away from offering patients, the PARP inhibitors here in the U.S. And, you know, we really need therapies that can effectively delay or prevent recurrence for these patient populations. So this, I think, is a real opportunity. You know, if we think about sort of what we do in this setting, you know, globally, bevacizumab is probably the agent that is used most in this setting. But, you know, it's overall in the phase 3 trials, it's a 2 month-4 month, you know, progression-free survival benefit from bevacizumab over as a maintenance therapy. So it's not something that is giving us a huge bit more than we need. We want more for these patients. It's also a more straightforward space, and I think this is, you know, you know, I think that, you know, this is. There's a more unified, sort of accepted standard of care that people agree that you do. Once you get into, you know, recurrent platinum-sensitive disease, it gets a little bit more sort of what is your control arm gonna be and what are you gonna go up against? It's a little bit harder to define, because there's just less of a unified practice. So I like this adjustment. Yeah, Tyler, let me just... Because I get, I've been asked this question a lot, and Joyce, you know better than anyone, you know, globally, of all of our investigators. You know, and I've been saying we didn't make this change because we're not confident about azeno's ability to be combined with chemotherapy. We were very excited about your presentation at ASCO. We believe the ability to combine this drug with chemotherapy safely not only differentiates it from adavo, but it also creates an opportunity outside of ovarian cancer. I know we're talking about ovarian cancer today, but this, you know, the reality is patients facing cancer get many of the drugs that you layered on top of azeno, or we layered, you layer, layered azeno on top of. I just was hoping you could kind of comment on that in terms of that wasn't necessarily what went into our thinking. It was that there was just a clearer, larger opportunity to move azeno into the first-line setting. But, you know, I think the audience would value your kind of opinion on this and feedback about azeno's ability to be combined with chemotherapy. Yeah, no, I, I totally agree. I mean, we, we have a lot of patients who have gone on the 002 study. We absolutely. I think azeno can combine with chemotherapy. I think there's, you know, some exploration still of the combination and finding the right dose with gemcitabine, which I know that my colleagues in our GI g roup are very excited about for their own reasons. But I think that, you know, the decision, excuse me, the plan to go forward into the first-line maintenance setting, I think is, you know, I'm excited about it not because of the question of combination with chemotherapy. I just think there's a real opportunity there, and it'll, you know, as we were talking about, you know, a straightforward path. Okay, Dr. Liu, maybe I'll ask you a few questions. There's a client question here that asks, "How many HRP patients actually go on to Bev in the U.S. and outside the U.S.?" If you can answer that, and also how much niraparib use there is in HRP or HRD negative as well. So I will be honest, I don't see, you know, I don't, like, see the global numbers and the U.S. numbers exactly. What I can speak to is sort of what we've sort of think is probably going on in the community, recognizing it's a very dynamic range right now. In the U.S., I think there's sort of a split. There's maybe about 50% uptake of Bev in the frontline setting. Globally, it's actually much higher. So if you look globally, bevacizumab is the preferred standard for maintenance therapy for these patients with HRP disease. In the U.S., it's actually probably bevacizumab, and then there's some thought for some people, maybe you don't put people on maintenance therapy, which is less of an accepted idea outside of the U.S. population. I think that, you know, for a while it was Bev or PARP inhibitors, but with the emerging data about PARP, there has been movement away from giving PARP inhibitors to patients with HRD test negative cancers. And I think with that, you're also, we're also going to see, this is my projection, I don't know this, I don't have data to support this, but I suspect we're actually going to see that bevacizumab use for these patients with HR proficient cancers is gonna continue to increase in the U.S. It has been on the rise. Okay. And you think, like, if positive azenosertib, Bev combo data was generated in a pivotal study, that would hopefully accelerate that uptake? ... Oh, yeah, I think people would be very interested in doing it. Yeah. Okay. And for the patients in the frontline maintenance setting that are getting Bev, what type of outcomes do they have? What is kind of the treatment duration or median PFS that you would expect? So if we look across the trials, you know, there, you know, it's probably somewhere in, you know, the 12-14-month range of maintenance therapy. So that doesn't count the time. That doesn't sort of include the time on chemo. So if you look at the different trials, like DUO, GOG-218, they include the time on chemo as part of the progression-free survival. PAOLA-1 has basically the maintenance time alone. So it's somewhere in that probably 12-14-month period. Okay. In a pivotal trial, if it was azenosertib Bev combo versus Bev, how many months do you think it would need to add on top of Bev to be exciting to you? I think if you could add on, you know, 4-6 months, it would be fantastic. I mean, Bev, Bev itself was approved off of a 2-4-month PFS benefit. I think that, you know, would be significant for most of us. Kim, maybe a question for you is, and maybe Dr. Liu, whoever you think is best to answer, but just combining with Bev, is there, like, potential mechanistic, you know, synergy, or do you view it as more of an additive approach and you're not concerned with overlapping toxicities? Curious to just get more thoughts on the potential combination. Yeah, well, I'll answer, and then maybe Joyce has a couple other comments. You know, we feel firmly convicted that there is no mechanistic reason why the drugs would be antagonistic, so then that it becomes to... You know, we believe there will be additive benefits because the drugs, both drugs, have benefit in azenosertib as monotherapy activity. There is some limited data in the literature that tumors that have high replication stress, which is a lot of ovarian, but in particular, Cyclin E-positive ovarian cancer. There's at least one study in the literature saying that that might predict additional benefit from Bev in combination with chemotherapy. So that's a little bit of a tangential data set, but we believe at the very least, they'll be additive. Joyce, I don't know if you have any other comments about this. Yeah, no, I think, like you said, Kim, I think there's not a lot of data out there about the combination, but mechanistically, I don't see a reason why they would be antagonistic. Okay. Yeah, and I'll just say one other thing because it, it's reflected in the rest of our portfolio, especially as we think of where ZN-c3 will be best in combination with molecularly targeted agents. There's no overlapping clinical tox with Bev and ZN-c3. So again, making it very attractive in the maintenance setting, as opposed to maybe even adding, like, a ADC on top of Bev. Like, you know, what, what you see if you look across Bev's clinical toxicity profile and then the ZN-c3, there's not, there's no overlap really in anything of any significance, which makes this, again, fed into kind of our thinking of the opportunity to have an oral drug with no overlapping tox with Bev, compared to, you know, other drugs that are further behind us in the development. Also, and kind of empowered our thinking about moving the drug into the first-line space because of what we think will be at least additive efficacy and no overlapping talks. Okay. And, Kim, you were pretty clear that, you guys didn't necessarily make this change to the frontline maintenance setting as a result of anything you saw with the chemo combo or anything new that was concerning. So I guess just to elaborate on why you made the change since ASCO, was it basically in consultation with KOLs and these working groups that led you to believe that it was a more attractive strategy? Well, I'll, I'll let Joyce chime in, but I'll answer. It was, you know, opportunity, clear path, loud demand from our investigators, not because they weren't excited about the second line study. But given the changes in the PARP prescribing practices that are, are happening globally, given that we have an oral agent that, as I just mentioned, doesn't have overlapping toxicities with Bev, given that we want to help as many patients as possible. And the reality is it's a, it's a much more straightforward trial than what we were facing with a clear standard of care, which is single-agent Bev. All arrows pointed to making this, this small adjustment. It's a different patient population, but it's still demonstrating the benefits of azenosertib. The reality is, is yes, there will be a delay in the initiation of the study, but the conduct of the study, given the larger number of patients, given a clear comparator, given that, you know, it's, it's a two-armed study. We've not disclosed all the final details of the study, and we're committed to doing that in the second half of next year. We believe that this is a, at, at most, a few months delay in actually getting a readout, moving it into the first line. And I don't know, Joyce, if you want to comment on just kind of just broad strokes. You participate in a lot of these first-line maintenance studies, like any other things that-... We, as a company, should be aware of, or, you know, any comments on what I just said, which is, at the end of the day, it's a more direct question with a clear standard of care. And we actually believe that will help accrual, help the conduct of the study. But I'll turn it over to you for any other thoughts. Yeah, no, I, I totally agree with all of that, and I think I was alluding to it earlier as well. I think it's just - it's a real opportunity. It's a real space of unmet need. And I think it is - it's a clearer question to be able to ask, because the standard of care, the accepted standard of care in this space is very clear. I don't think anybody would argue that bevacizumab is an accepted and potentially the preferred standard of care worldwide, for these patients. Okay, that's great. Very helpful. Kim, maybe another one, a client question for you. So, this client asked if, I guess at ASCO, there was any regulatory feedback or if the FDA suggested that you guys should do the frontline maintenance instead of the chemo combos for any reason? No, this was a company-driven decision based on the things we've already discussed. Okay. And it wasn't based on anything we saw. We remained very excited about azeno being able to be combined with chemotherapy, again, in ovarian cancer. But, you know, I think we're not moving in this direction. We haven't disclosed it. But again, these chemotherapies and the activity we saw was durable efficacy. Joyce can speak to it, and it was a safe combination. We were able to get to a recommended phase two dose with three different types of chemotherapy, which I think really speaks to the safety and the efficacy of the combinations. Joyce, and it's your study, I mean, it's not your study, but you certainly presented it at ASCO, so I want to make certain you get your two cents worth in here, too. Yeah, no, I think it's been very exciting with chemotherapy. As I said, we, you know, we continue to be very excited whenever slots appear on the study to be able to put our patients on. And, you know, we have seen patients benefit and have durable benefit. It's good. Okay, that's great. Another client question as a follow-up to the chemo combo discussion. Kim, do you guys plan to update the chemo combo data in the future with more follow-up? We've not committed to an exact timeline, but absolutely. We've, as I said in June, we're continuing, and Joyce just alluded to the combination of gemcitabine and azeno has always been a promising one. Preclinically, they're highly synergistic. That Taxol and carboplatin are also highly synergistic preclinically, and I think it reflects in the clinical data that Joyce presented. So, and I've said this, like, I, I'm very excited about the chemo combinations. We've got gemcitabine combinations ongoing in what I'll refer to as Joyce's study, but it's 002. It's a global study, not just in ovarian cancer, in this study we've been talking about, but we also have it in combination, as Joyce alluded to, gemcitabine and azeno in pancreatic cancer, in an investigator-initiated study. We have committed to presenting the results of the gemcitabine azenosertib combination in osteosarcoma, small data set, phase I. So we'll actually have three different patient populations treated with the combination of gemcitabine and azenosertib. That's, you know, how excited we were about the preclinical data we were seeing and really the data, the preliminary data that Joyce presented at ASCO. Yeah, that's great. And then maybe just a couple final questions, because I think we've answered most of the client questions, just on timelines and cash runway. But first, maybe on the timeline. Kim, you discussed this briefly earlier, but I think it'd be helpful just to wrap things up and elaborate on it. The azenosertib to get to market in platinum-sensitive ovarian cancer with this change to the frontline maintenance setting, you know, clearly there's a delay in getting that study started, but in terms of getting to market, how big of a change do you think it will be in terms of getting to market once you get the final data? Yeah. So we've not disclosed the timelines around the adjusted trial design going into the first-line maintenance. What I will say is that there's a number of trials that have been conducted in that space, not necessarily limited to HRP. And Joyce might have to help me out with this, but PRIMA, I think PAOLA and ATHENA, all enrolled patients in that maintenance, and I'm sure there are more, but at least those are the numbers that I have kind of stuck in my head that are in the public domain. You know, enrollment took somewhere between 24 and 27 months, even in the setting of ongoing PARP, competing ongoing PARP maintenance with over, you know, similar patient populations. And then, you know, the, the readout happened about, just roughly 48 months after the first patient went on. So I think, you know, that's what's in the public domain. We're committed to updating, not updating, but providing the timelines very similar to what we did earlier this week in the PROC setting. But I think those three studies, I'd be interested in Joyce's opinion, really help us with a benchmark in terms of sites, the length of first patient on to last patient off, and then the duration of follow-up. I just want to point out, though, that in HRP, which is typically, you know, the HRP wild type, meaning not BRCA mutated, and we showed that on the patient flow. There is a general perception, I think the data supports it, that the duration of therapy in Bev in the maintenance setting is slightly lower than those patients that are HRD positive. And so those timelines really reflect all ovarian cancer patients, because that's what those trials enroll, not necessarily a shorter duration of therapy that we see in those studies when you specifically look at either HRD mutations or HRP patients. I know that was a lot, but I think those are very conservative time guidelines based on what we know the performance of single agent Bev to be in the maintenance setting in HRP patients, which is what we're going after. Joyce, did I say anything wrong there, or do you have anything to add on those kind of just guidance numbers? No, I would agree with that. And I mean, again, as you were also saying, I mean, all of these studies were, like, enrolling at the same time. I mean, these were all large phase III studies in the frontline space that basically enrolled concomitantly and both enrolled and hit their sort of planned timelines very well. So I think there's just, it reflects the, the need and the hunger for these agents, and especially now in the HRP or HRD test negative patient population, where we have a big recognition in the GYN community that these patients need something different than what's available or something more than what's available. I think these will be... This, this will be a very attractive trial, will roll very quickly. Okay. Maybe one last one, and for you, Melissa. What's the current cash position and runway, and has the runway changed significantly as a result of the new PSOC development plans? Yes. No, the short version is no, our cash runway has not changed. We have over $500 million cash on hand, and that'll take us across all the milestones we've been talking about and more across 2024, 2025, and into 2026. And with this, this adjustment and strategy, which we're very excited about, our runway remains into 2026. Okay, wonderful. Well, I think we've asked all the client questions. I want to thank both Kim and Melissa for spending the time to talk through the recent updates, and especially Dr. Liu, for joining us. We'll let you get back to your patients, and hope everyone has a great weekend. Thanks, Tyler. Thank you so much. Thank you, Tyler.