You just entered into agreement to kind of reach a resolution with those activist investors. Maybe you can just kind of start with the basic framework of that cooperation agreement that was reached, kind of how it came together, and now just what it means for the company going forward. Sure. Yeah, before I do that, I have to say that I have to defend zandelisib and say that it was an outstanding drug that we really should be selling right now. It was completely differentiated from other PI3K delta inhibitors, but you know, FDA just really soured on the entire class for its use in indolent lymphoma, and we got swept up in all of that. It was very unfortunate. So we were driving toward commercially launching that drug this fall, and so once we, you know, didn't have a path to accelerated approval there or even certainty around what endpoints FDA was looking for in our controlled pivotal experiment, we and our partner, Kyowa Kirin, decided to wave the white flag last year, as you say. So that's led to, you know, a downsizing, a right-sizing of the company, going from around 106 employees down to around 34, January 1, we'll be at. So we've had, yeah, a lot of adjustment in the last year. And part of reacting to all of that was also trying to be opportunistic in getting a later-stage asset. As you mentioned, we were pursuing the acquisition of Infinity. That was voted down by the activists, and now, as you also said, we have entered into a cooperation agreement with them. You know, what that agreement allows us now to do is to turn over the data cards for our two programs next year and give us the freedom to do that. The principal terms of the agreement are that there's a standstill through our next two AGMs, which basically takes us through calendar 2024, so plenty of time to get through our current clinical programs and interpret that data and potentially, you know, get some kind of third-party validation if the data is encouraging. Some other provisions of the agreement are that we're doing a two- potentially two distributions, definitely one distribution of $1.75 a share, which is roughly $11.65 million, which will be issued December sixth. And then a second potential distribution that's tied to our one of our clinical programs, our ME-344 program. There is a kind of a built-in futility analysis in the protocol that says in the cohort of roughly, you know, the first 20 patients, if we didn't see a PFS of at least four months in four patients, then we wouldn't, you know, advance to the next cohort. And so we kind of tied that to a potential distribution to give the stockholders downside protection. So that's, I think, what they were really looking for. Mm-hmm. And the other pro-- kind of main provision was, we have three new board members that replaced the three that were standing for election or re-election this December. One's designated by Anson, one by Cable Car, and what was mutually agreed to by the company and Anson, Cable Car. And there was a committee, a capital allocation committee, that was formed to advise on strategic considerations and budget. So those, I think, are the principal terms of the agreement. Okay. I don't disagree with your assessment of, of zandelisib. Thank you. I appreciate that. It's a good drug. Yeah. Just wrong place, wrong time. Yeah, really. Yeah, exactly. So maybe we can start with the Voruciclib. And, you know, maybe just in talking about this, you can provide some background on the asset, kind of where it came from, what you've learned about it in clinical development thus far, and then the rationale for why you're combining this with venetoclax and the ongoing relapse refractory AML trial. Yeah, sure. So we acquired the drug from a company called Presage, which is a private company in Seattle. They have... They're really a technology company that has a device for micro-injecting tumors in vivo. It's called CIVO, and then they can micro-dissect the tumors and use fluorescence to show synergy between various drugs. And they showed a really profound synergy with this drug, Voruciclib, which is a CDK9 inhibitor, and the BCL-2 inhibitor, venetoclax. And that's what got us interested in it. Matt Davids, the Dana-Farber investigator, that was really a key player in developing venetoclax, was very enthusiastic about this particular compound and combining it with venetoclax. And so we licensed it from Presage. And what we've learned so far is that the drug... So first we did a. You know, we're still in phase 1, and we did a monotherapy, a single, you know, ascending 3-by-3 trial. That took some time because of COVID, and now we're actually in the escalation of combining with venetoclax. And what we're seeing is really encouraging. The investigators are very excited about about what's going on. We're just now getting into doses that we think are going to have plasma concentrations that will inhibit MCL1, and that's what we're seeing now because we're doing you know, we're kind of doing real-time PK, and we're sampling all of the patients, and we're seeing a few things. We're seeing that, you know, the main target really, which is... Well, it's CDK9, but then we're inhibiting RNA polymerase II, which is really the mode in which all the effects downstream are taking place, is being inhibited in patients. We're seeing biological effects, such as like patients going transfusion-free for, you know, while they're on the drug. We're seeing blast counts go down. These are in relapse AML patients, and we are seeing some responses, and so we're pretty encouraged. These are patients that 90% of whom have experienced venetoclax. Most of them are, you know, getting venetoclax upfront. That's pretty much standard of care at this point. So that's why, you know, even at the first dose of 50 mg, we were seeing some activity, so we're pretty excited about that. Okay. The other thing I should mention is we're not seeing any drug-drug interactions because that was something that, you know, I guess FDA was theoretically concerned about, and we're not seeing that at all. Okay. Yeah, I know DDIs have been- Right ... historically problematic with venetoclax. Mm-hmm. So this drug I know is highly potent against CDK9. But when you look at the preclinical IC50 data, right, it also suggests that it's fairly potent against some other CDK isoforms- Mm-hmm ... like 4 and 6. I think we haven't seen any of that kind of characteristic 4 and 6 toxicity show up- Yeah ... in any of the safety data. So I guess, how do you just explain that kind of differential between, you know, these, these IC50 values- Mm-hmm ... the potency of the drug, and then the safety tolerability data that we've seen today? Yeah, that's a good question. I think it's just the difference between measuring, you know, on plastic versus in cells. We've got more recent data in cells that show a 4-fold increase in resonance time for 9 versus 4, and a 40-fold for 9 versus 6. So I think that pretty much probably explains that. Okay. And I know on the safety front, right? So you're talking about inhibiting CDK9, which has this downstream effect on MCL1. Mm-hmm. We've seen other companies try to develop inhibitors against MCL1. Some of those have run into cardiotoxicity issues. Mm-hmm. Have you looked closely at any cardiac biomarkers in the data that you've generated to date? And then, I guess, what does that data tell you? Yeah. So we haven't—what we've done is ECGs and clinical observation, and historically, the drug had been looked at in various solid tumor patients at, you know, up to 800 mg in a single dose, and I think up to, like, 650 daily, and we just haven't seen any cardiotoxicity at all. And we certainly haven't seen it in our current studies in AML or in B-cell malignancies that we've looked at in combination or as a single agent. Okay. You've also chosen an intermittent dosing schedule for this drug. Mm-hmm. and I think there's, you know, some investors who look at intermittent dosing with a little bit of skepticism. I know that it was a little bit of an intellectual barrier to entry for some folks who were looking at zandelisib previously. Mm-hmm. I guess, what are you trying to avoid from a toxicity perspective? Mm-hmm ... in dosing intermittently? And then what are the PK properties of the drug? You talked about residence time, that allow for intermittent dosing without really diminishing- Mm-hmm ... target engagement and clinical benefit. Yeah. So what we observed in the single monotherapy dose-escalating data, it might have been a little bit of bad luck, but we ran into some pneumonitis in a couple of patients that were stem cell transplant patients, and so that could really be. And they had G- you know, graft-versus-host disease, so that leads to a lot of vascular leakage, and that can lead to pneumonitis. So we don't even know really if it's drug-related, honestly, but that's what kind of, like, got us into shunted us into the intermittent dosing. And we'll see. We're still doing. You know, we're still assessing dose and schedule. We'll see where we come out. We've not seen that again. It was just in these two stem cell patients, and we've now, you know, allowed stem cell patient, transplant patients to come back in, and we haven't seen it, we haven't seen it again. So that's the. That's what got us into intermittent dosing. You know, I'm not too sure why. I know people, maybe investors don't like it. It's funny because with zandelisib, we looked into this a lot, and it's, you know, practitioners don't mind it. Like, they actually dose venetoclax all the time in this relapsed AML population- Mm-hmm ... on an intermittent schedule, and it isn't really a problem. And I know with zandelisib, you know, we were, you know, you can always just make placebos and have somebody take a placebo on the off days, and they still are taking something every day. And we did focus groups in follicular patients, and didn't seem to be a problem at all. But, you know, we'll see. The properties of the drug that allow for it are that it's got a long half-life, you know, probably somewhere around 24-28 hours, and it's got a very high volume of distribution, so it gets out-- it's kind of similar to zandelisib in that way. It gets out of the plasma and into tissue. That's more relevant, obviously, for solid tumors than for hematologic malignancies. But, you know, we'll see where we end up. You know, it's not definitely gonna be two weeks on, two weeks off. That's just where we are right now. Okay. So you talked about the ongoing trial in combination with the venetoclax relapsed/refractory AML. Most of these patients, as you mentioned, have progressed on prior venetoclax. Mm-hmm. So what do we know about venetoclax retreatment outcomes? Mm ... in this setting? And I guess, are there any kind of guideposts in the clinical literature- Mm-hmm ... that you can use to kind of better understand or support the attribution of benefit that you're seeing with Voruciclib? Yeah, that's a great question. There's not a lot of information out there. When venetoclax was originally being developed, there was a small cohort of something around 20 patients that were relapsed AML patients, and they had. It had, like, a 20% response rate, and of course, that was in a completely venetoclax-naive population. Now, virtually everybody's getting venetoclax upfront, and there's not a lot of data in the literature on how those patients fare. But there's a big difference, honestly, between a patient that progresses while on venetoclax and a patient that is venetoclax experienced and, you know, is off therapy for a while and then progresses. Mm-hmm. I think, like, the median survival is, like, two months for the former and, like, 11 months for the latter. And so it really depends on who exactly you're talking about because that relapsed population is pretty heterogeneous, and that's gonna be something we're gonna have to really look at when we get this data set, and to know about, you know, the standard we're shooting for and to, you know, design trials going forward. But, I, you know, I think, you know, we've talked to people who, like, develop venetoclax and the clinicians, and I have to say, I think, like, 20% response rate seems to be the kind of, you know, floor, the table stakes, you know- Mm-hmm ... and then anything north of that, people get pretty excited about. Like, that's what I'd have to say, but I really have to emphasize that it depends on, like, exactly who you're talk- you know, what the natural history of a patient is that you're looking at. Mm-hmm. And so when you establish the eligibility criteria for this study- Mm ... are you requiring patients to have progressed while on venetoclax? No, we're not. We're not, we're not right now. I mean, we're in phase I, and we're trying to define dose and schedule, and I think that would be too, just too hard to recruit- Mm-hmm ... that study right now. So, but going forward, I mean, again, we'll have to see what we see, and, we'll have to, like we said, we're looking at, like, you know, inhibition of RNA Pol II, and we're looking at some other things, and we'll have to, you know, really pair that up with responses and how patients do to design the next study. But right now, we're not, we're not requiring that. It's just, you need to have, you know, you just need to have be a relapsed patient. But like I said, 90% of them have had venetoclax. Okay. I know you've also generated some phase I data with this asset in the setting of solid tumors. Mm. Maybe you can just kind of talk about the mechanistic rationale there, and I guess, do you have any development aspirations? Yeah ... in solid tumors? We, you know, it's CDK9. We've shown, and the previous owners of the drug have shown that we can lower MYC expression, and so that's what stimulated the interest in solid tumors. But honestly, we have to be kind of laser-focused right now and really focused on heme malignancies and combination with BCL-2 inhibition, so we don't have any immediate plans. We're exploring it, or we actually, I think we have an ad board coming up, like, on the seventeenth or something, to talk about solid tumors. But I think, you know, the plan would be if we partner the drug in the future to, you know, more broadly go into solid tumors with resources of, you know, of a partner. I don't think it's something that we're gonna be able to pursue in parallel. I think that the more interesting opportunity right now would be, you know, if you see a strong signal, a compelling signal in the relapsed AML population, you kind of in parallel would go after the relapsed population and, and maybe even go up front and do a triplet versus a doublet and... But you know, all of that takes resources, so, you know, that's why I think we're pretty interested in partnering. Okay. And then just how should we be kind of thinking about the cadence of- Mm ... data disclosures that emerge from the- Mm-hmm ... AML AML trial over the course of the next 12 months? Yeah. I think, so what we're contemplating is we're going to complete the dose ascension, and we'll have that earlier in the year, and then there's built-in expansion cohorts once we, like, really settle on a dose, and that data will be a little bit, you know, later in the year. And they're small expansion cohorts, but I think it'll be informative enough to guide us going forward, as to whether, you know, there's a there there. Okay, maybe we can switch to ME-344- Mm-hmm. -which was the mitochondrial inhibitor that you talked about earlier. Which I think that description to me as a headline seems a little scary. Right. But it's obviously a lot more nuanced than that. So maybe you can just kind of explain, you know, what this drug is mechanistically doing at the level of the mitochondria. Yeah. So, we're doing, even, you know, more work to exactly understand precisely what the drug is, you know, the protein target of the drug, so to say. But what we know is that it inhibits ATP production, and the oxidative phosphorylation process in the membrane of the mitochondria and de novo pyruvate biosynthesis. So, the idea with that drug is that you know, the tumors are very plastic and very flexible in their ability to produce energy. They typically do it through glycolysis. And so if we're going to, we want to combine this drug with what we're using. The early work was done in VEGF TKIs, a variety of them in various mouse models. But we had a window study in breast cancer patients with our collaborator at CNIO in Madrid, where he dosed ME-344 for one cycle while patients were waiting for mastectomy in combination with Avastin. And then he was looking at Ki-67 scores for proliferation. And if you look at the ME-344 plus Avastin group, there was a like a 23% reduction in Ki-67. And in the Avastin alone arm, there was a 186% increase in Ki-67. And that kind of gave us some encouragement that this VEGF inhibition of glycolysis and angiogenesis, combined with inhibiting oxidative phosphorylation in the mitochondria, would be a way of really you know impeding tumor growth. And so then we looked where Avastin is being used, and we had a bunch of ad boards, and we settled on colorectal cancer. Because the physicians were very confident as to what Avastin in kind of a, like, a third or fourth line patient population would look like, and they'd be able to discern a difference with the combination therapy. As far as, yeah, like, the kind of scary tox thing, it's... You know, the cancer cells are really highly metabolic, and they're, you know, probably one of the most metabolic cells in a normal, in normal person is neurons. And if you go at high enough doses, like, that is the dose-limiting toxicity of this drug. Mm-hmm. It's peripheral neuropathy. But at the dose we're using, which is 10 mg per kg, we don't see any peripheral neuropathy. And it's a pretty tolerable drug, which is one of the things that we're encouraged about. Because when you look at or what the physicians are telling us kind of about, like, Lonsurf, is that it's not the most, you know, tolerable therapy to take. So, you know, it's a commercially interesting market to go after. It's a good proof of concept, and if we show that we can synergize with VEGF inhibition, you know, we can go elsewhere. I mean, that's used in a number of settings. Okay. So this Phase 1b trial you're now running in colorectal, it's two-staged. Mm-hmm. You've established this efficacy threshold in Cohort I that, you know, needs to be achieved- Yeah ... in order to proceed to Cohort II. And I think the cooperation agreement we talked about earlier is referencing that. Right. Maybe you can just talk about the threshold that you've set. Mm-hmm. And then why you think that threshold is an appropriate- Mm-hmm ... surrogate form of clinical benefit in this setting specifically? And then why achieving that threshold would give you confidence in a Stage II and perhaps even a larger study. Well, I think, you know, it's. You have to understand the reason it was set a while ago when the protocol was first being written, was that this is a total novel concept. And the physicians were just saying, like: "Okay, look, like, let's just look at 20 patients, and let's make sure that we're getting at least a 20%-ish, you know, four-month PFS rate in this initial cohort of patients before we, you know, move on." As kind of like, you know, as a threshold, right, to advancing the trial further. It's like, as I said before, it's more of a futility analysis. It's not necessarily what we think would be like a, an, you know, commercially compelling profile, right? Mm-hmm. You know, a TPP that we're necessarily shooting for. It's just what the criteria that we're set to go and advance into Cohort II. You know, there is the Lonsurf in third line data, it's like 43%, four-month PFS. So clearly, there is a higher, I think, hurdle for commercial viability. Okay. So- ... and then, but sorry, I should say also- Yeah ... and we said, 'cause we talked about this in the earnings call. Again, it really matters like who you're talking about, because we're getting a hodgepodge. We're getting a bunch of patients that are kind of, you know, fourth line or fifth line, and, you know, as well as maybe second line, and, whether you've got somebody who's had Lonsurf progressed versus just like platinum up front, that's a very, you know, different assessment of how the drug's performing. So again, we have to kind of go patient by patient through- Mm-hmm ... the trial and see how the drug performed before we can make a final assessment about its, you know- How stringent are the guardrails that you've put around eligibility criteria to try to narrow some of that? Yeah, they're not- Kind of- It's just, again, it's just, they just have to have relapsed. You know, they just have to be- Mm ... relapsed patients in colorectal. Yeah, that's it. Okay. And you talked about the cooperation agreement. Mm. I guess if you don't achieve this quote, unquote, futility look- Mm. Mm-hmm ... you pay out another distribution, correct? That's right. Yeah. Well, it's in the protocol, it's framed in a positive manner, that once you get four patients that have at least four months PFS, you advance to Cohort II. In the agreement, it's more framed in the negative that, like once you have seen 17 patients that progressed prior to month four, then that triggers the distribution, or if the board, for some reason, decides to terminate the program prior to Cohort II, that would also trigger the distribution. Okay. And then how are you just thinking about kind of the timing and disclosure of this initial Cohort I data? Is this something that you would provide in the format of, "Yes, we did. No, we didn't? Mm. Or do you want to provide more granular data around the 20 patients that are gonna progress to Cohort I? Yeah, you know, we haven't thought... I mean, all we've thought about so far was just the guidances out there, that, which is, you know, we're gonna have Cohort I data by mid-year, and so that's all, you know, I can say right now. We haven't really had a discussion any more granular than that, honestly. Okay. Yeah. And then maybe just lastly, you can talk about the balance sheet and just kind of what that allows you to- Mm-hmm ... to execute on here over the course of the next 12 months or so. Yeah. So, I think we ended the quarter with around, like, $82 million in cash, and that allows us to go out. I think the guidance now is 12, you know, 12 months, so that's more than enough time, as I was saying in the beginning, to get the data from the two current programs as they're designed. You know, look at expansion cohorts for Voruciclib, and you know, get third-party validation, hopefully, if that's the path that we wanna go down and the data is compelling, whether that's in the form of, you know, partnering or doing a financing, but I think we've got, you know, the runway to do all of that. Okay. Very good. David, really appreciate it, and thanks for joining us. Yeah. Thanks, Steve. I appreciate it. All right. Thank you. Thanks, guys.