Hi. Welcome everyone. Good afternoon. So my name is Roger Song, one of senior analysts covers MedTech, biotech at Jefferies in the U.S. Our next company is GlycoMimetics. Welcome. Hello. Thank you. Thank you, Roger. Awesome. So maybe kick this off by, you know, what is your, updated elevator pitch for the investors in terms of the overall overview of the company with the recent updates? Yes. Thank you, Roger, and thank you for Jefferies for this opportunity. GlycoMimetics is a clinical stage company, actually now a late clinical stage company, with an upcoming phase III readout in the next few months. So we're very excited about the timing. It's been a long journey, arduous journey, but we're getting very close to our data readout. We are very focused on glycobiology. That's our, that's our home brew and really our passion for the last 20 years. Our lead asset is an E-selectin antagonist called uproleselan, and we are currently in a phase III with 388 patients fully enrolled, and we have said that data will be available in Q2 2024. So before end of Q2 2024 is when our data readout is in the relapsed and refractory AML setting. Awesome. I have to say, I cover 30+ companies now, and the GlycoMimetics next year data readout is one of the most kind of anticipated readout in my coverage. Maybe we can focus on that trial first. It's your lead program, lead indication. Let's focus on that first. So you have a definite timeline for the data readout. What agreement you have reached with the FDA, how you come up with that timeline? And the follow-up question is, what kind of data you have seen along the way? You say it's a long journey. It is, you know, take a, you know, 36 months median follow-up. Along the way, what kind of data you have seen in the blinded fashion, data you have seen, what give you the confidence you will be able to report the data by the time? Yeah, thanks, Roger. So our trial is a straight-up uproleselan in addition to salvage chemotherapy versus salvage chemotherapy in two different forms, MEC and FAI, two cytarabine-based therapies that have been widely used in the last 40 years for fit salvage chemotherapy patients. So you know, the baseline is quite established in the market. There's a lot of data, and those patients typically live between 6-8 months. That's been the historical median overall survival. We have added uproleselan to half of those patients. So the whole idea was that this trial should read out much faster. It has been taking much longer because patients are living longer. Now, obviously, we don't know why that is happening. That's why you do big phase IIIs to see the data. Part of our, you know, discussion with the FDA was, well, if this is taking longer, there is a point where the database would be mature enough, and we have aligned and agreed that that point is in Q2 2024, driven by, one, the fact that by then it will be a median follow-up of three years, so three years in a relapse and refractory AML population. We're debating, is this the longest or one of the longest? And second, the vast majority of patients who have gone to a stem cell transplantation will have two years plus data of follow-up post-transplantation, which is a very meaningful milestone since patients who have had a transplant and have gone to live for another two years, typically are a long-term survival population. That's what we've seen from the different databases. Now, obviously, along the way, we have access to pooled, blinded data, so I would just stress that it's pooled and it's blinded. Obviously, we see the median overall survival. We see the median MRD negativity rates. I mean, the whole thesis of what we're trying to do is get more patients into deeper durable responses, getting them to transplantation and through transplantation by not adding any safety signals. So we see that, we see obviously the responses in a pooled way, and we're excited. We're excited that patients continue to live longer, and soon we're gonna find out what's driving that. And so stay tuned, but it's now months away, not years away, as it used to be. Yeah, finally. And so, understanding you, you give us, like, a broad kind of statistics related to those blinded pool, the blinded data, maybe without giving us too much specificity there. But compared to your phase I, remember, you got a BTD and published the phase I data. Compared to that trial, you know, how you compare the phase III versus phase I/II results regarding those pooled blinded data, and how do you interpret that data in terms of the play in favor or, you know, kind of deviate the OS kind of expectation for your phase III? Yeah. So as our phase III data readout kept on getting projected outwards and delayed, obviously, we're getting a lot of questions. What's driving that? Is it the patient population? So at one point, the question was: Are the patients the same? And we have released that data showing that our phase III patient population enrolled in that is typically in line with our phase I/II patient population. Then the next question was, well, is there a significant dropout? If you remember, you were one of the- Yeah ... people asking, "Is there a significant dropout in the phase III?" And we have released that number saying, "Well, that's, it's actually 3%." It's a very low number. Then the question was... Well, during COVID, was the enrollment curve, there was, was there any aberrations about that? And we released, released that curve, basically showing it was a very smooth 388-patient enrollment curve, with the first couple of months of the pandemic having a softening. But then, you know, things picked up and continued to pick up until we had last patient in, in November 2021. So all these milestones during the time we were getting all these, these questions in terms of how are the patient enrollments different? Then on the other side, when it comes to the outcomes based, the big question was: Well, what are you seeing in terms of transplant rates? We have seen in our phase I transplant rates of about 31%, and what we have indicated in our phase III transplant rates are north of 31%. Mm-hmm. Obviously, people ask us, is that with a capital N, with a small N, is how far? We haven't given guidance on that, but it is higher than that number. So typically, the patients that we have enrolled in the phase III, they are the typical relapsed and refractory patient population, in line, not just with our own phase I/ II, but also in line with other clinical trials in the same setting that have been running over the last few years. Mm-hmm. Yeah, great. So maybe another question is, you know, we know the final analysis well, it's approaching pretty quickly. Do you plan to, you know, release additional pulled unblind, blinded data to investors, or you're gonna keep it the same way and then wait until the final results coming out? Yeah, we've been very disciplined, Roger, in terms of how we move our data forward. And it's really where we are now, is we have two opportunities to really get to that final readout. One is through the original plan of an event-based trigger, where, you know, if we get to the 295 events that we have disclosed we need in this trial, then that triggers the primary analysis, or the newly negotiated route with the FDA, which is through the time-based analysis. And that's kind of what we were talking about, that we are going to get there one way or the other and have that press release, hopefully, obviously, if all this is, if the data is, is holding on, to say we've met the top-line readout, the results to be, announced in a medical conference. That's kind of how we're thinking, which is, which is in line with how typically this, this happens. We, we don't plan at this point to release any other pooled blinded data because you can interpret it in different ways. It's very difficult without giving additional details. And we're so close now at this point that let's, let's wait for this data to mature in the next few months, and hopefully, we'll release it a positive top-line readout. It's fair, right? So you don't wanna create additional, like, uninterpretable kind of data, again, adding additional, kind of maybe noise. And then so understanding you can report the final data one way or the other, time-based or the event-based. Based on current model, I know you keep tracking those kind of overall survival events pretty regularly. Based on current model, do you think how likely you're gonna report the time-based or versus the event-based? Basically, what's the event rate looking like in the past, few months? Yeah. So I mean, for the benefit of everyone, we have had over the last 18 months, two slowdown in the number of events that have happened. The first slowdown was last year, which triggered us to go to the FDA and have a negotiation in terms of including an interim analysis that was not planned in the beginning of the trial. So that was the first time we have indicated that there was a slowdown. And then the second one was even after we did the interim, there was a further slowdown in the number of events. So the number of events have been slowing down, which triggered us to go yet again to the FDA and have the conversation to say: There is a point where the database will be mature, even if we're not at 100% of the predetermined events. Keeping in mind is that in the beginning of this year, we were already at around 80% of events. So this is something we had disclosed, that in the beginning of December of 2023, we were around at 80% of events, and give it another, call it five quarters, so we will get wherever we get. And then even if that doesn't happen, the opportunity we have at hand is, even if there are a few stragglers and, you know, hopefully, they'll live as long as they can, that's not gonna be impacting the maturity of the database. We are still going to be able to deliver the database before Q2 2024. Got it. I think clinically it makes sense, you wanna do this time-based. We don't wanna wait indefinitely for those events to happen. It may not happen. You know, we just don't know. I think that makes sense. Regulatorily, any precedent, such kind of a shift from the event-based to the time-based? I believe we have a couple, even within AML, such kind of case, and that give investor confidence, okay, that's a viable regulatory path, to shift the, the primary endpoint analysis. Yeah, I mean, as it happens, to your point, Roger, there is a regulatory precedent in AML in this space, actually, with the first targeted therapy in AML, which was midostaurin by Novartis back in 2017. I used to be the U.S. head of hematology at the time for Novartis, so I know that example well. And it was very similar in terms of getting to a point where negotiating with the FDA on a time-based analysis, and that in that case proved out to be a positive outcome, and then we launched the drug, and that was a great thing for patients to do. So there is regulatory precedent, not just in hematology overall, but specifically in AML. and we, you know, many of us have actually worked on it, and we have a lot of folks who know that, and of course, the FDA knows that as well. So, that would be an appropriate surrogate for, you know, for us, in our opinion. Yeah. Yeah. You know, we all, we all hope this trial can work kind of positively, because one or the other, those patients live so long, that's good for the, for the space. You know, either chemo outperform so much, which, to me is unlikely, or this uproleselan is really adding significant benefit to those patients. So yeah. Yeah, I mean, MEC and FAI have been around for many, many years. We have so many different trials, be it on, you know, randomized or, retrospective single center view. So we have a lot of ranges of data that comes, and then on top, we're adding uproleselan. The key thing to keep in mind is that our phase I was actually two cohorts of patients. Mm-hmm. We had the relapsed refractory patient population. Based on this, we have started our company-sponsored trial, the phase III, that we're currently talking about. But in parallel, something to keep in mind, that the NCI has taken a look at the other cohort, which was the frontline, fit for salvage chemotherapy, elderly patients, and based on that, they started a parallel NCI-sponsored trial, which is a phase II, adaptive phase II/III trial. And they have fully enrolled that patient population, 267 patients across the NCI centers. Last patient in was December 2021, two weeks after the full enrollment our own phase III. Mm-hmm. So that's something, you know, also to keep in mind, is that that is an EFS primary endpoint for the phase II subset, and they have not reached the EFS from what they told us yet. Mm-hmm. EFS is typically read before the overall survival. So in our view now, we have two pivotal trials, you know, together there are 650 AML patients that are taking longer than typical in their readout. One in the relapsed refractory setting, in combination with MEC or FAI, and the other in the frontline setting in combination with 7+3, which is the standard. Yeah, it is amazing. So, you know, maybe you say, "Okay, one trial for some reason, it just works in the way," but we have another trial, literally, just like you said, you know, compared to the well-established standard of care outcome, which is way outperform the whole thing. So let's see if that trial and the combination... Okay, so before we talk a little bit more about the NCI trial, you will read out the relapsed refractory phase III data, Q2 next year. Now, how—what's the kind of format you're going to give us the, the feedback, you know, the results in terms of the top line versus later kind of medical meeting, kind of a detailed data? Yeah, that's in discussion currently, Roger. So I mean, as a minimum, we would have the header, just like, you know, most companies do that, and we got to make sure that we're balancing that with not jeopardizing any medical conference submission. So we want to make sure that that happens. So that's going to be, you know, quite a typical approach. And from there, what we have also said is that we're rapidly going into NDA submission mode. So we have committed that before end of year 2024, we plan to submit an NDA, should the data be positive. Got it. Top line, like a hazard ratio, p-value, and then later on, we're going to have the full kind of data in the medical meeting. Yeah. We're trying to see what we can disclose in addition to the top line that doesn't jeopardize us from any, you know, medical conference afterwards. So we'll see how that would work out. Yep. And then you guided you will submit an NDA, assuming positive, submit NDA by end of 2024. What are additional work you need to do beyond the phase III, and to be able to submit an NDA? Yeah, I mean, at the end. So our team has been working on the NDA. We have enhanced our regulatory teams for some time. Remember that we had done an interim analysis in the beginning of the year, and although it was a very high bar, and we had only put 5% alpha on the table, but there was also always a possibility we crossed that high bar. So we had to be ready from a regulatory perspective to move into the next step. So we have done a lot of data cleaning. We have done a lot of preparations in terms of, you know, getting ourselves in a situation where we can rapidly submit the NDA. But we also want to make sure that we do it appropriately, given that this is it, you know, we want to make sure that the data is clean, all our specificities are done. So that will happen over the summer, and then hopefully, we should have a smooth NDA submission. We've been having conversations with the FDA. I mean, we do have breakthrough designation, we have fast track designation, we have orphan status, so that gives us a lot of opportunities for discussions. As we've disclosed, only on the launching the trial, we've had two major alignments with the FDA within a 12-month period. So that gives us an excitement that that positive discussion will continue to happen. Yeah, that's true, and seems FDA pretty accommodative, kind of in terms of your request and, based on the status of the trial. Right. Well, the thing is, I mean, AML patients are. I mean, they need options. They need options, especially if you're fit for intensive therapy. We really need to drive overall survival. We need to drive durable responses, not just surrogate markers. That's very, very important. And our mechanism of action is such that it's agnostic to cytogenetic profile, it's agnostic to mutational profile, agnostic to what's the backbone therapy. So these kinds of options are really, really needed in the marketplace, and we believe the FDA's openness is really driven by that, the patient need. Yeah. I talked with a few AML, CLL, you know, when I asked them what would be the clinical meaning for extension of the OS. They say if you can, you know, prolong the OS by 3 months for those patients, relapse refractory, they think it's meaningful. I think that's how you power the study anyway. Correct. That's how it's powered. So it's not just, you know, from a statistics perspective, but also clinically meaningful perspective. We hear that a lot as well. Those are patients who typically live between 6-8 months. If you're adding that, you know, at least 3 months, that's really meaningful, you know, clinically as well as being statistically significant. Yeah. Okay, let's talk about the NCI trial. It's a first-line fit older population. Honestly, I'm expecting you're gonna report it at any time. You know, I just read it for every morning. I say, "Okay, you're gonna do that," because that's EFS endpoint. Supposed to, you say it's closed enrollment December 2021, that's almost like, two years. I never heard of any, like, EFS trial readout for AML patient, for that long. So what have been, kind of... What have you been kind of, communicating with this NCI? How's the dynamic look like? They just tell you, "Okay, nothing," and then you just, and waiting for the next update? Yeah, I mean, obviously, we're fortunate to have the partnership with the NCI, who has sponsored the trial. I mean, for a tiny biotech, that's a big deal, where they sponsor it and pay for it. We provide drug. And that's something which, you know, we've been doing for quite some time. In fact, our NCI partnership recently has expanded in AML to also include pediatric patients. That's something that we have recently announced on November three. So, with the NCI, we have continuous conversations, and that's part of our connectivity with them. The trial is run by the Alliance. The sponsor is the NCI. So the way it will work is that once the trial hits its trigger, its EFS, then the Alliance will let the NCI know, and then the NCI will let the company know. So that cascade has not happened. That cascade is active in terms of communication, but hasn't been, you know, hasn't happened in terms of, "Yes, we have hit an EFS." To your point, it can happen any day because, I mean, we're having anniversaries now on an AML trial, two of them going on. Last patient in was in December 2021, and here we are, almost in December 2023, and we're saying the EFS has not been hit, let alone overall survival. So we'll see when that happens, but yeah, to your point, you know, it is possible anytime that they might call us and say, "By the way, we hit the EFS. Yeah. Awesome. Yeah, look forward to that. I know it's a bit early, but, you know, since you are in the pivotal, what's your overall commercial strategy for AML and what's the total, total addressable market for uproleselan in AML? You know, you have two pivotal trial running, but also you have a couple, you know, investigator-sponsored trial targeting, you know, different segment of the AML. So what's your overall, kind of market opportunity you think for uproleselan and the commercial strategy? Yeah. So you know, we believe uproleselan has the power to be a very important tool in the toolbox of hematologists across the AML spectrum. From the frontline, all the way to very difficult to treat, not only in relapsed refractory, but secondary AML, for example. So the whole idea is that, you know, can we combine it with different therapies where we can enhance and deepen responses and not add any safety signals? And that's been something very important that we've been monitoring as well, and we haven't really seen any major safety signals in with uproleselan in AML, and we know that's a hot topic within AML therapy, so we're fortunate from that perspective. So the market, the addressable market is quite big and quite broad. You know, obviously, it's not gonna happen from day one. We got to start, you know, as our data comes in. Currently, our lead is in relapse and refractory patients. In a way, that's a very concentrated business because, when physicians, you know, those physicians are, you know, as an example, 40 centers across the U.S., that's about 80% of the relapse and refractory patients are treated in these. So it's a very concentrated area. We can reach those physicians very rapidly, and we have the know-how. Over the last couple of years, we've actually been enhancing our teams with folks who've done this before in AML with the same physician target and making sure that that connectivity is really very strong, so when the data comes, we're able to move very rapidly. So that's in the relapse refractory, but then the frontline is as big, if not even bigger of an opportunity. And of course, as we're going through our two pivotal trials, we have, to your point, multiple additional ISTs that are enrolling patients, be it in the unfit patient population with Ven/Aza. That's the trial that Dr. Jonas is leading in UC Irvine, in UC Davis, or in the very difficult to treat secondary AML population, where Dr. Kadia and his team at MD Anderson have been advancing that trial, and I believe they're gonna have an update on that as well at ASH. So the whole idea is that we believe uproleselan can really be a very pivotal therapy in combination with other therapies across the AML board, not just in a very specific, you know, mutational area, but really across the board. Yeah. Excellent. Maybe last a couple minutes, you know, the GlycoMimetics company is founded on top of a glycobiology kind of platform, so you do have some other early pipeline. So recently, you started a trial phase I, 1687, for the sickle cell. So what's the status there, and what should we expect for the initial data readout? I believe it's 1Q next year. Correct. So, you know, that's the beauty of our platform, is we have multiple, you know, therapies and you know, multiple glycomimetics, coming on. So as we got clarity about the timing of uproleselan. That really helped us go back to our budget and ensure that our CFO and his team, you know, find us the money so that we can start the phase Ia of our second generation E-selectin antagonist. Remember, this company was very, very focused on sickle cell disease, and that's part of our heritage, and a lot of us who've joined over the last few years also have worked in sickle cell, and we really understand this patient population. We've learned a lot from our first generation E-selectin antagonist, and we've taken a lot of those learnings and really designed 1687 to be, you know, multiple times more potent and on E-selectin subcutaneously bioavailable. So the way we look at 1687 is, can we get to a point where a patient having a vaso-occlusive crisis actually is able to take, like, an EpiPen-like approach and, you know, just at the start of their vaso-occlusive crisis, be able to either self-administer or do it without having to be admitted? That's the vision with 1687, and we've had 400 patients in the previous generation, so we've learned a lot from that, and we're trying to take these learnings to 1687. So what we were able to do is actually start the phase Ia because now the funding as well was available, that really drives that vision that we have in sickle cell forward. So stay tuned. Q1, we're gonna have data. Obviously, it's gonna be much more of a safety focus. I mean, this is a phase Ia, but the whole idea is that in addition to our work in uproleselan in AML, we're able to start this work in sickle cell. That's actually very helpful 'cause we believe that tens of thousands of patients, sickle cell patients, I mean, hopefully, they're able to take the cell and gene therapies. We will see with the price tags, what would happen. And of course, the preventive, prophylactic approaches have been in the market for many years. We know the uptakes and the market shares of this, and I can say it's been humbling at best. So we believe there is a huge opportunity of patients who are going to have vaso-occlusive crisis, and they just need that, you know, point of care so that they're able to, you know, break that cycle of pain very rapidly. Awesome. Okay, last question, your cash position and what's the runway guidance? Yeah, we've been fortunate in the beginning of this year to bring in additional quality investors in addition to the ones that we have, our long-term investors that we have. And we have enhanced now our cash position so that we're—we have a cash runway until December 2024, and now we have the definitiveness of our data readout in Q2 2024. So that's really created an opportunity for us where, we, you know, we don't have to worry on the short term to, to get to those major milestones. And of course, if the major milestones are, are positive, we would be in a very, very different place. It's been a great journey so far, and we really look forward to delivering not just uproleselan's first data, but the full power of our glycobiology-based platforms really soon. Yeah, look forward to the exciting 2024. Thank you for the time.