Okay, good morning, and thank you everybody for joining us at the JMP Securities Hematology and Oncology Summit. We're really excited to be joined next by Syros Pharmaceuticals. Really timely conversation this morning, given the announcement of some very positive data in newly diagnosed AML patients. So we will obviously be talking about that. We have several members of the management team here. Conley Chee, newly appointed CEO, and I know it's day three, I think, officially on the job or so. And we also have Jason Haas, the CFO, and David Roth, CMO. So thank you, guys, and Conley, maybe I'll just turn it over to you to give a quick intro, and then we'll jump into the Q&A. Sure. Yeah, so thank you, Jason. Yes, it's day 3. It's been quite a pretty tremendous 3 days. And so, as Jason alluded to, we have some data that we just released this morning, which we're really excited about, and maybe if we have time, we can go into some of that. But, here at Syros, we've been around for about 11 years now, and we've been focused on genomically guided treatments, of which, you know, our lead asset is tamibarotene. And, we are now in sort of the late development stage for this program, and so we're really excited by that. And so it's been a pretty good 3 days so far. So, appreciate the opportunity, Jason. Absolutely. And obviously, day three as CEO, but you've been at the company for longer than that you know, focused primarily on the commercial readiness activities. So maybe if you could just give us, you know, your experience so far of Syros, and your vision, how you look forward for the company. Yeah, it's a great question. So, yeah, as Jason says, I've been here for about two years now, just over two years. I joined with the other Jason that's on the call about two years ago. It's been a fantastic journey so far. So we've laid the groundwork, I would say, for and a blueprint towards launching. And so our intent and our strategy is to launch tamibarotene on our own in the U.S., and have that commercial presence in the U.S. And so the plans are quite detailed. We know basically when and where we need to make investments in order to have a successful launch. Luckily, the many, if not all of the investments that we'll need in order to ramp up for launch will occur after our data readout, our CR data readout, which we expect in mid-Q4 of next year. But I would say in the near term, and based on our data that we released this morning, and certainly our momentum with our phase III MDS data, our MDS trial as well, I would say our priority number one is to finalize recruitment of our MDS program, which we expect in Q1 of next year, and again, to have that readout ready by mid-Q4 of next year. And then in the AML trial, we've just reported on roughly 20 patients this morning, and the idea is it's our Phase 2 development program, and that should, we should be able to share more data next year as well. So that's really our short-term priority in terms of development. And then again, our midterm commercial vision is well laid out internally. You know, we, we've talked about this before. You've been very focused on prioritizing tamibarotene as the lead asset. Can you just talk about that focus, why you're you know, you decided to single in on that asset and you know, a couple of things that have been at least paused temporarily. If you had a blank checkbook, obviously, you could do a lot more, but just walk us through the prioritization on Tami. Yeah. You know, our goal here at the company is really to have the biggest impact we can to patients, and that's been our number one focus. We recognize that, you know, tamibarotene is our best and nearest opportunity to do that. So with the MDS trial reading out next year, we decided that we really needed to focus all of our energies and resources against that program. We also have, as you alluded to, multiple earlier stage programs, one of which is our APL program, which is oral arsenic. We've decided, earlier this year, actually quite recently, that it's in a very good place right now, and so we're gonna pause the program. We're gonna continue with our tamibarotene development and hopefully launch. When more capital becomes available, our strategy is likely to renew that program. Great. So- It's all about, as you know, this market. It's all about really focus and making sure that we really bring our programs to life. And it's important that you have the cash in the bank to actually go and execute on those programs through those big milestones, which you have clearly stated. So, That's right. I'd love to focus on, you know, the topic of the day, AML. Before we jump into the data, maybe you could just give us the background here. Number one, you know, the trial design and why you're looking at the triple combination of Tami with Ven and Aza, and the patient population. Obviously, this is newly diagnosed AML patients, but also focused on RARA-positive patients, which is, you know, directed to the mechanism of Tami. Just walk us through the background here and why this is the patient population you're studying. Sure, Jason. So I'll take that one on. So as we know, venetoclax and azacitidine has become a standard of care for treatment of newly diagnosed unfit AML. And despite it having quite impressive activity, there's still a significant amount of unmet need. It only delivers responses in about two-thirds of patients, which leaves about 33% of patients without a CR or CRi. And the majority of the patients who do respond will end up eventually relapsing. So it's, you know, the durability is encouraging, but it's not a be-all-end-all. And we really feel that we can address unmet need by, you know, incorporating tamibarotene into the context of this treatment regimen. We have generated our own phase 2 data that supported the potential of tamibarotene in these patients in combination with Aza by itself. So we pursued this experiment in combination with Tami and Aza, and decided to do this in a randomized fashion so that we could very clearly see how the triplet is comparing to the standard of care doublet, all in patients who have RARA overexpression. The general design of the trial is a randomized phase 2, and it's aiming to enroll a total of 80 patients, 1:1 randomized into each of the two arms. It's the triplet of Tami-Ven-Aza versus the doublet. Everyone has newly diagnosed unfit AML. They've all been previously untreated, and they're all positive for RARA overexpression. They get Tami starting on day 8 of a 28-day treatment cycle. On day one, they start Aza for a week, and on day one, they start venetoclax for the duration, continuous daily dosing of venetoclax. The randomized trial is just taking Vidaza without Tami. The Vidaza is all dosed per label. Those are the nuts and bolts of the trial. We did have a corporate webcast earlier this morning, where we disclosed, for the very first time, very exciting data about the outcomes of this very first pre-planned interim analysis. I'm happy to just walk you through a little bit of that at a high level, unless you have a specific question before I do. Yeah, yeah. So I think we're gonna throw a slide up in a second, but- Yeah. Just before we get to the data, just walk us through that interim. So the number of patients, you know, the, where they are in terms of follow-up, et cetera. Just give us the context of this data cut. Sure. And then we'll throw the slide up in a minute. Yeah. So the study. Just to let you know, the study began enrolling patients in the first quarter of this year. This data cut was on November thirteenth. So, you know, we've got, you know, good data from these patients, but the focus has been on the response rates, the durability of response, event-free survival, overall survival. Those time to event endpoints are immature at this point in time, and so those will be the focus of a future presentation on these and additionally, enrolled patients. So, you know, as we've said previously, the majority of the patients have been at least through two cycles of treatment. You know, we have in our slides, you know, certainly, duration of treatment is in several patients out to, you know, over 6 to, you know, about 8 months, depending on, you know, on who contributed to that. So, you know, we've got pretty significant information that gives us good insight to how the drug is performing. I could probably speak to the results if you, you- Yeah, and as we do that, we can put the slide up now. Maybe just put it into context for us, what we were expecting. So what we were expecting with Ven-Aza, and then, you know, what you would have viewed as a clinically meaningful improvement over standard of care. Yeah. So the standard arm in its pivotal trial has delivered a 66% CR/CRi rate, and Tami/Aza, in our phase 2, delivered a 61% CR/CRi rate. We powered the study to show a statistically significant, and importantly, a clinically significant difference between the two arms. And of course, you know, we're aiming to address the unmet need, and by that, you know, I do mean focusing on those 34% who don't develop a CR/CRi and ultimately go on to progress. As you know, if a patient is treated with venetoclax and then progresses after the initial response, the outcome is rather dismal, with a median survival of only over 2 months. So, you know, we really do feel there's a fair amount of unmet need to address. And these are our results, which have shown the CR/CRi rate in the triplet of 100% on all patients out of CR/CRi, with a CR rate of 78%. And in contrast, the control arm delivered a 70% CR/CRi rate and a CR rate of only 30%, both of which are consistent with the pivotal experience with Ven/Aza. So, you know, we think these are very exciting. You know, the difference between the two arms is compelling. And I think another point to bring up is that this combination was well tolerated. We did not identify new safety signals, and probably one of the most important findings for safety... you know, I don't know if you wanna go to that next slide, is that we did not find evidence for added myelosuppression. Myelosuppression is when the peripheral blood counts are reduced because of toxicities of the drug on the bone marrow. It's often a bit of a healthy balance between eradicating the leukemia, but then poisoning the normal cells and not giving them a chance to circulate and protect the patient. So the drugs Ven and Aza are well known to have high degrees of myelosuppression, and you know, clearly, we were looking to see that we didn't exacerbate that. Now, tamibarotene is not known to be myelosuppressive. In fact, it's a differentiating agent, which may do quite the opposite. And so here we have the data that show the outcomes of the triplet in the dark blue and the doublet, Ven-Aza control in the lighter blue. And you can see the key hematologic adverse events, febrile neutropenia, neutropenia, thrombocytopenia, leukopenia, and anemia. And the results really don't demonstrate that we worsen the situation. In fact, for a few of them, the ones that are largely focused on the white count, the febrile neutropenia, the neutropenia, and the leukopenia, it appears somewhat favorable with higher rates of side effects on the control arm. So- And David, is there a biological rationale for that to be better versus, you know, is this just small numbers? You know, and it's not different, it's not worse. So, the answer, I think, is yes. And potentially, the fact that tamibarotene is known to regulate the expression of genes involved in myeloid differentiation and can be associated with differentiation or, you know, the growth of blood, the development of blood, the normal maturation of blood. In contrast, the mechanism of action of the other drugs is not that, and is known to have myelosuppressive side effects. So, we think this non-overlapping mechanism of action and non-overlapping baseline toxicity profile may be contributing to this. And, Jason, I do wanna add another thing, which is somewhat exciting. You know, when we look at these data, but we did see a higher rate of complete responses. And on the venetoclax arm, 70% had CR/CRis, but there were only 3 CRs. The other four were CRis. And the difference between a CR and a CRi is that while they both have reduction in bone marrow blasts, the CRi doesn't have complete normalization of the peripheral counts. And so in this instance, you know, this side effect profile, it dovetails nicely with the clinical efficacy readouts. And so the two datasets together further strengthen the totality of the outcome in our opinion. And, you know, may be very important. Look, we're gonna have to follow these over time, and we're gonna have to see this in additional patients. But I will say that our data over many years have been consistent. You know, we started off as a single agent in relapsed patients. We added AZA in as a doublet in relapsed and then newly diagnosed patients. We had our earlier safety lead-in data with the triplet in venetoclax. These are just continuing to build a consistent dataset that gives us confidence, that, you know, reassures us and reaffirms our, our conviction in the future of the trial. Got it. So then, as we look forward here, you know, again, you know, you're continuing to enroll, you're continuing to accrue, you know, time, as it were, so, so durability. Just walk us through the, you know, when we'll get data, the next data update. Yeah, so we're continuing to enroll. We at this point had 23% of the patients on. We're, you know, guiding toward 80 patients is our, you know, total enrollment. We haven't said when we'll hit that 80. We do believe we will be providing a meaningful update of data in 2024. Again, we haven't said specifically when, but that should be, you know, an interesting update because we would expect we'll have more information on the immature data of today in terms of durability and additional information on the more recently enrolled patients at that point in time. And Jason, you didn't ask, but I will proactively offer up some insights into our MDS trial, because that's our pivotal trial. Right. And that's our study that's gonna lead to our first approval. And there, we are focused on one endpoint for the approval. The primary endpoint is complete response with evidence of durability, the remission rate. And you know, the way we look at these data, the tolerability profile, and the correlation of that with CR rates. You know, you don't CRs, you need normalization of blood counts. So we think this really bodes well for the drug tamibarotene to deliver the CRs that we're looking for in the MDS program. Got it. And we're very excited about that. I mean, obviously, it's a different regimen. This that's just with AZA, this is with venetoclax. But in some respects, if you can demonstrate this with a more, a more aggressive regimen, you know, it should be, I think, straightforward. I, I don't wanna overspeak, but, but we, we are- And I do wanna dig into MDS. Sure. But just before we do that, maybe, you know, to wrap up the AML conversation, and maybe, Conley. Yeah this is one back to you. Let me ask it in this way. It obviously, we need, you know, more patients, we need the durability, but if the data play out as they look like they could, or should, what would be the argument or the pushback against this becoming a, you know, the triplet standard of care? Why would a physician not choose to use the triplet instead of a doublet? Yeah, you, you tell me. I don't, I don't know. I mean, this is, this is pretty powerful evidence from at least- Right the near-term efficacy perspective. And if it bolds out the profile that we think it will, which is sort of, you know, significant responses, rapid responses, as David has pointed out as well, and without added toxicity, I think it certainly has the opportunity to be standard of care. And the only thing that physicians need to think about is the testing in order to identify patients with RARA overexpression. And we'll, I think we're gonna make it very easy for physicians to do that. It's a PCR test, so it's not very complicated, and the results should come to them fairly quickly as well, as you know, opposed to some of these multiplex testing and so forth, that are out in the market. So we're very bullish that if this profile holds up, there's a tremendous market opportunity, because there's great unmet needs still in AML with the overall survival the way it is, and CR rates. Clearly, a lot of commercial prep work to do, but it seems like a fairly straightforward, you know, commercial message, right? Yeah. You're not changing standard of care, you're adding on top of standard of care. This should be fairly straightforward for physicians to understand and to act upon. Yeah, I think so. So Ven-Aza has been the standard of care for quite a while in unfit AML. We're going to add on top of it, again, an unbelievably good potential profile to add on top of that without added toxicities. And so physicians have learned to manage the Ven-Aza profile, and adding on tamibarotene with a quick, you know, test, which they're doing broadly anyways in diagnosing the patient. I think it's gonna be fairly easy to adopt it as standard of care. Yeah, and Jason, I could just wanna add one minor comment additionally to say that, you know, and I'm a hematologist who's cared for these patients, so I could speak from experience. But when one has an opportunity to identify a patient with a targeted therapy that is, has a higher probability of working in that patient, you know, we typically go for it. And so- Yeah. You know, we've identified that about 30, you know, a third of the patients don't respond to Ven-Aza. You know, we believe that if we can identify RARA-positive patients with our test, which we clearly are doing in our trial, and then we can bump the response rate to, you know, such a high number, you know, we'll have addressed a significant unmet need. And, you know, all this while, you know, behind every one of those responses, there's a patient who's benefiting out there, so we're really excited about it. Fantastic. So switching back to MDS, I guess. So again, just walk us through the background here. Obviously, you know, AML and MDS are, you know, along a spectrum. Can you just walk us through why you chose MDS and actually chose MDS as the first pivotal program that you ran are running? Yeah. So there's you know, clear understanding, biologically and clinically, that there's large overlap between MDS and AML. There's multiple shared underlying mutations and drivers. In fact, we demonstrated elevated RARA gene expression in both diseases. We have generated data initially in relapsed higher-risk MDS, where we've seen marrow blast reduction, hematologic improvement, a durable, complete response of the marrow, in higher-risk MDS. And then we saw compelling clinical activity with our doublet with Aza. That was largely focused on the newly diagnosed AML setting, but we did look at a subgroup within there that had lower blast count AML. Now, when I was a hematologist in training, MDS was defined up to 30%. AML started at 30%. The cut points have dropped. I guess I'm aging myself. But now if you have AML, it's 20% or higher. So if you look at that, that window of patients who used to be higher-risk MDS years back, and now they're called AML, we saw an even higher CR rate of 67%. So our clinical data really informed our thinking. And the last point is that we’re ready to go. We had data with Aza and Tami in that whole- study population, and the standard of care for MDS is just the one drug, Aza. So we were immediately ready to jump in with our safety data and profile and start an experiment adding on to Aza. The Ven-Aza experiment in AML required this step that we're going through to first prove that we can do it safely, and then to see the clinical activity, so we could think about the proper way to set up a registrational trial. So- I think the moment was there, and we seized the day, and that's why MDS led, you know, led the way. Got it. And I know we only have a couple minutes left here, but I wanted to talk about. You started talking about the trial design, David. Maybe just give us the regulatory background here. What have you confirmed with FDA in terms of what is approvable? And then you, well, no, last year, sorry, earlier this year, you announced the decision to expand the trial and include an overall survival or fully power the trial for overall survival as well. So, the trial can serve as its own confirmatory study in some ways. So if So if you could just- Sure. So we vetted everything very carefully, obviously. And we've sought, we've obtained alignment, obviously, on the use of Aza as a comparator, on the focus on patients who were positive for RARA overexpression, on the general elements of the trial design. You know, obviously, the statistics and the powering is over 90% powered, and the use of the complete response rate as the primary endpoint. We've been in receipt of feedback that the CR rate, combined with the duration of CR, can serve to support a full approval, but it can also serve to support an accelerated approval with the subsequent need to convert that to a full approval. And, you know, that traditionally would be based on demonstrating survival. Now, we know that, there's high correlation of CR with durability and overall survival. So, you know, we have, you know, conviction that there's a real meaningful opportunity to get an accelerated approval based on the CR rate alone or a full approval based on the guidance. If we were in a situation where we received accelerated approval, we would then need to do a separate trial. And then through additional discussions and, you know, basically everything that, you know, we understand to be the expectations, there's a preference perhaps for using a single trial to deliver the confirmation. And we know there's a strong interest in having progress towards a confirmatory trial at the time of the initial regulatory decision. We amended the trial to power it for the key secondary endpoint of survival. That means that it's now gonna enroll up to 550 patients, but we're still gonna do the analysis of the 190, as originally planned, to see if the primary endpoint delivers on the CR. And then the trial will be well underway to enrolling toward the 550. So not only is it efficient it's, it's economical, you know, and it, it spares resources. We don't have to repeat the 190 patients. We, you know, use them for the survival purpose. And the investigators already would be familiar with the study, you know, so the mechanics, the tactics, the trial's up and running. It's a highly efficient way to do it. Sounds like. So- I know we're running out of time here, and it's a big question to end with, but maybe just put it into context for us, you know, the unmet need here and how you see Tami being incorporated into the treatment paradigm. Yeah, tremendous unmet need in both counts, right? So if you look at MDS, roughly there's 21,000 patients in the US and Europe diagnosed annually, and as David has pointed out, there's really no good therapy. So the standard of care has been there since 2006, and it's not because it set a high bar, right? The CR rates of azacitidine are somewhere around 17%, as they read out in their pivotal. And so we have the opportunity to really make a big difference in these patients. And so of the 21,000, we expect that 50% of them will be RARA overexpressers. So tremendous opportunity there. And then in MD... AML, as you saw the results, also adding on to the standard of care, to the roughly, there's 25,000 AML patients in the EU and the US annually diagnosed. And 30% of those will be RARA overexpressers. And again, to add our drug onto the standard of care in a targeted way, I think would be very beneficial to patients, and so, tremendous commercial opportunity on both counts. Great. Well, congratulations again on the data this morning. Thank you. That's really good, good to see. And then I'll also look forward to next year with more readouts. So, Conley, David, Jason, really appreciate you being with us this morning, and we'll look forward to seeing the progress. Thanks so much for the opportunity, Jason. Yeah. Thank you so much. Thank you. Have a good rest of your meeting.