Good morning, and thank you for joining the GlycoMimetics KOL event. Please note that this event is being recorded. Today's remarks will be followed by a question-and-answer session with the management team. Please dial in via telephone to participate. I would now like to turn the conversation over to Christian Dinneen-Long, Company Counsel at GlycoMimetics. Please go ahead. Good morning. Today, we will review comprehensive results from the pivotal phase III study of our lead drug candidate, uproleselan. A press release was issued this morning, and the slides being referenced on this call are available on the company's website at glycomimetics.com. This call is being recorded, and a dial-in phone replay will be available for 24 hours after the close of the call. The webcast replay will also be available for 30 days in the investor section of the company's website. On the call today from GlycoMimetics are Harout Semerjian, Chief Executive Officer, Dr. Edwin Rock, Chief Medical Officer, and Brian Hahn, Chief Financial Officer, who will join for the question-and-answer portion of the call. We're pleased to also be joined by Dr. Dan DeAngelo, Principal Investigator for our phase III uproleselan trial, GMI-1271-301. Today's call will include forward-looking statements based on our current expectations. Forward-looking statements may include, but are not limited to, statements about the potential indications, benefit, and impact of the company's product candidate, uproleselan, analysis of data from the company's sponsored Phase Three clinical trial, planned or potential regulatory interactions, the progress and timing of the National Cancer Institute's sponsored clinical trial of uproleselan, including expectations regarding data readout from that trial, potential development plans and activities, and the company's cash burn and budget plans. Such statements represent management's judgment and intention as of today and involve assumptions, risk, and uncertainties. GlycoMimetics undertakes no obligation to update or revise any forward-looking statement. For information concerning the risk factors that could affect the company, please refer to our filings with the SEC, which are available from the SEC or through the GlycoMimetics website. I'll now turn the call over to Harout. Thank you, Christian, and good morning, everyone. Over the past month, the GlycoMimetics team has been diligently and rapidly evaluating the results from our data-rich pivotal phase III study. We have worked with medical, statistical, and regulatory experts to understand the full scope of the results and their implications for relapse and refractory AML patients. This morning, we're excited to share our comprehensive findings for the first time. Though the study did not meet its primary endpoint of overall survival in the intent-to-treat population, there is a wealth of data that outline how pre-specified stratification factors have impacted survival outcomes for patients. These include backbone therapy or backbone chemotherapy, disease status, and age. For instance, uproleselan achieved a clinically meaningful improvement in median overall survival for patients with primary refractory AML of 31 months versus 10 months in the placebo arm. This is unprecedented in such a difficult-to-treat patient population. On today's call, Dr. Ed Rock will provide a brief overview of the pivotal study as well as its primary analysis. Next, we are very pleased to welcome Dr. Dan DeAngelo, the study's principal investigator, Professor of Medicine at Harvard Medical School, and the Chief of the Division of Leukemia at Dana-Farber Cancer Institute, who will present more detailed study results. I will then highlight our plans moving forward based on these results and open the call for questions. Let's turn the call to Ed. Thank you, Harout, and thank you all for joining us today. I'll begin with study design. As a reminder, this study enrolled 388 patients with relapsed or refractory AML across 59 sites in nine countries. Patients were randomized to uproleselan or placebo, with both treatment groups receiving investigators' choice of either MEC or FAI chemotherapy. Enrollment completed in November 2021, and the study had a low discontinuation rate of 3%. In June 2023, the FDA cleared addition of an optional time-based primary analysis, and the time-based analysis was triggered with a March 31, 2024, data cutoff. This trial was stratified by known prognostic groups, and the large study size by itself yields additional subgroups. Three randomization strata ensured balance across treatment arms of these subgroups as follows: First, investigators' choice of backbone chemotherapy with either MEC or FAI generated two groups, each with a total of 194 patients. Second, disease status subgroups include primary refractory with 128 patients, early relapse with 50 patients, and late relapse with 210 patients. Lastly, by age, 218 patients under the age of 60 enrolled versus 170 patients at least 60 years of age. We spent the past month evaluating these pre-specified stratifications, as well as other subgroups, to identify correlates and potential predictors of uproleselan benefit in AML. As we disclosed on May 6, our phase III study did not meet its primary endpoint with a hazard ratio of 0.89. Nonetheless, results trended in favor of uproleselan. More deaths occurred on the placebo arm, and more patients on uproleselan remain alive today. Also, importantly, control group median survival of over a year is unprecedented for a randomized, relapsed, and refractory AML trial and sets a new benchmark for treatment of this disease group. When looking at the overall survival figure, you can see that the curves begin to separate after one year, which is suggestive of an immune-mediated effect. The uproleselan curve is the upper line on this figure and shows an increase in survival at the plateau. Moving on, the study's key secondary endpoints included induction, emergent, severe oral mucositis, complete remission, and remission. Oral mucositis rates were balanced across treatment arms, while response rates trended in favor of uproleselan. An additional secondary endpoint of post-treatment hematopoietic cell transplant rate was high on both arms, 52% on uproleselan and 51% on placebo. Finally, as an exploratory endpoint, the trial evaluated measurable residual disease, MRD, at end of induction. MRD negative responses consistently favored the uproleselan arm in every response category, including complete remissions, as shown on this table. Now, I'm pleased to introduce our next speaker, Professor Dan DeAngelo, who is the study's principal investigator. I'll now turn the call over to Dr. DeAngelo. Thank you, Ed. I appreciate the introduction. I'm going to now walk you through the selected results and significance of this trial, including randomization, stratification, as well as other correlates of overall survival and high-level safety. This large, pivotal phase III study of uproleselan in the relapsed refractory AML population contains a wealth of important clinical information. On this slide, you can see that uproleselan survival results are broken down by stratification factors, each of the subgroups of interest and potential markers of activity of resistance. I will walk you through survival benefits in various subgroups, in particular, for groups demonstrating uproleselan clinical activity, including the FAI backbone chemotherapy, the group of primary refractory disease, as well as patients receiving post-treatment transplantation and patients achieving an MRD negative disease response at the end of induction chemotherapy. First, let's start with the backbone chemotherapy. In this study, patients were dosed with investigator's choice of backbone, either MEC, consisting of mitoxantrone, etoposide, cytarabine, or FAI, consisting of fludarabine, Ara-C, cytarabine, and idarubicin, with a large number of patients, 194, treated in each arm. Patients treated with MEC backbone chemotherapy, shown in the left curve, had a hazard ratio of 1.06, which is near unity and indicates no uproleselan benefit. Correspondingly, median overall survival of patients treated with uproleselan and MEC was 8.7 months, compared to 12.3 months for patients treated with MEC alone. By contrast, however, the hazard ratio of 0.73 was seen for patients treated with FAI, showing a strong trend in favor of uproleselan. Equally striking was the median overall survival of patients treated with uproleselan plus FAI, which was 30.2 months higher than the 12.8 months with FAI alone. The GlycoMimetics team is further analyzing these results to learn what may account for these divergent results between backbone chemotherapies. For example, baseline imbalances and adverse prognostic features. Interestingly, patients. In contrast, results with MEC versus FAI chemotherapy were not observed in patients who received hematopoietic transplant, and you can see these on these Kaplan-Meier curves. The hazard ratios were low at 0.52 and 0.66 for MEC or the FAI groups, respectively. Also, the median overall survival in the transplanted patients treated with uproleselan was not reached, regardless of the backbone chemotherapy used, whereas the median overall survival in transplanted patients treated with chemotherapy alone, that is, on the control group, was 24-26 months, respectively. Although this particular analysis looks at subgroups of subgroups, late separation of the survival curves mirrors what is seen in the intent-to-treat population and supports uproleselan clinical activity in patients who received subsequent stem cell transplant. I'm going to next discuss the subgroup analyzing disease status. As a reminder, there were 128 patients treated with primary refractory leukemia, 50 patients with early relapse, defined as less than six months, and 210 patients with late relapse. The primary refractory patients treated with uproleselan had an overall survival hazard ratio of 0.58, with a nominally significant confidence interval, not crossing unity. The median overall survival of 31 months on the uproleselan arm versus 10 months on the placebo is clinically meaningful for this very difficult-to-treat patient population. This benefit was not observed with uproleselan in either the early relapse or the relapse group of patients. Response rates trended in favor of uproleselan over the placebo group in complete remission and remissions, as well as the duration of remission. Importantly, you can see that the median duration of response was not reached for the patients with primary refractory leukemia treated with uproleselan and chemotherapy, compared to a median response duration of only 12.7 months on the placebo arm. These results again underscore the meaningful, durable responses of uproleselan in the primary refractory setting compared with chemotherapy alone. Importantly, uproleselan survival benefit in the primary refractory setting was agnostic to backbone chemotherapy. Uproleselan plus MEC generated an overall survival hazard ratio of 0.71 compared with placebo, while the uproleselan plus FAI had an analogous hazard ratio of 0.55. Another factor affecting survival outcomes is measurable residual disease negativity status. In this study, 144 patients achieved an MRD negative status. MRD negativity correlates with successful outcomes in patients with acute myeloid leukemia. In this study, patients achieving MRD negativity that is on uproleselan had an overall survival hazard ratio of 0.49 compared with placebo. Correspondingly, patients treated with uproleselan did not reach median overall survival, while MRD negative patients in the placebo arm had a median overall survival of 24.1 months. Transplantation status is another important subgroup for the study. Overall, there were 200 patients who received a transplant and 188 who did not receive the transplant post-study. Transplanted patients on uproleselan had an overall survival hazard ratio of 0.59 compared with placebo. Correspondingly, transplanted patients achieved a median overall survival of greater than 2 years, while the median overall survival in transplanted patients treated with uproleselan was not reached. For comparison, median overall survival for non-transplanted patients was 4.2 months in the uproleselan arm and 6 months in the placebo. These are clinically significant findings, as transplantation is the only known cure for patients with primary refractory acute leukemia. Interestingly, patients treated with uproleselan who received a transplant did not reach median overall survival, regardless of the backbone chemotherapy utilized. Likewise, the median overall survival for transplanted patients in both placebo arms was comparable: 24.4 months and 26.3 months for MEC and FAI, respectively. Rounding out this data set, let's now examine safety and tolerability of uproleselan. Prior studies established results for uproleselan support that uproleselan has no known drug-drug interactions. It has no CYP-mediated effects and no dose-limiting toxicities, as well as no known QTc prolongation or differentiation syndrome effects. Adverse events were consistent with known side effects profiles for respective backbone chemotherapy regimens, including for treatment emergent adverse events overall, grade 3 or higher adverse events, serious adverse events, and discontinuation due to adverse events. Again, there were no known significant adverse events added to the backbone chemotherapy with uproleselan. In conclusion, taken together, these data support the clinically meaningful disease activity of uproleselan, including patients receiving FAI chemotherapy with a hazard ratio of 0.73 favoring uproleselan, as do the median overall survival of 30.2 months on uproleselan versus 12.8 months on placebo. In the setting of the primary refractory patients, these patients demonstrated a hazard ratio of 0.58 favoring uproleselan, with median survival of 31 versus 10 months on uproleselan versus placebo, respectively. Median duration of remission was not reached for the primary refractory patients in uproleselan plus chemotherapy. Importantly, transplanted patients had a hazard ratio of 0.59 favoring uproleselan, while median survival of transplanted patients on placebo was greater than 2 years. Median overall survival for transplanted patients treated with uproleselan was not reached. Lastly, adverse events were consistent with known side effect profiles of chemotherapy, consistent with the prior known safety profile of uproleselan. ... These data set support the use of uproleselan primarily in this high unmet need of primary refractory patients with acute myeloid leukemia. I will now turn over the call to Harout. Thank you. Thanks, Dan, for that clear summary of the data and the important examination of the treatment landscape in AML. These results demonstrate uproleselan's potential to address a significant unmet need for certain AML patients. Up to 40% of adults with AML will have persistent leukemia following intensive induction chemotherapy. Despite availability of new AML therapies, the treatment of primary refractory disease remains challenging due to low response rates to salvage chemotherapy and poor overall survival rate. As you can see on this graph from a meta-analysis of almost 9,000 AML patients, the red line indicates the survival of refractory patients, which is unfortunately not good. As per the NCCN and ELN guidelines, the current standard of care for this population remains salvage chemotherapy. The only curative treatment is a hematopoietic stem cell transplant, which is strongly recommended for all eligible patients. With these limited treatments, only 10%-12% achieve a complete response with salvage chemotherapy, and only 20%-30% of patients who receive hematopoietic stem cell transplants have a five-year overall survival. This is one of the longest randomized placebo-controlled studies in relapsed and refractory AML, with a wealth of informative-important data across subgroups. We have worked diligently and efficiently to understand these results, as we owe it to the patients and to the entire AML community. We plan to discuss this data with regulators to determine a potential path forward for uproleselan in settings such as primary refractory population. There are three important factors that we took into consideration when determining our current plan. The first is the clinical factor. There is a high unmet medical need, as primary refractory AML is an aggressive disease associated with very poor outcomes. This population desperately needs new treatment options. The second factor is statistical. Median overall survival in primary refractory patients on uproleselan arm was 31 months versus 10 months in the control arm, with a hazard ratio of 0.58 and a 95% confidence interval that does not cross unity. This increase in overall survival is unprecedented in this patient population. The third factor is a potential regulatory pathway. The primary refractory patient population is clearly defined, easily identifiable, and has a high unmet medical and patient need. Given the robustness of our database, we look forward to engaging with the regulatory authorities. In parallel, it is important to remember that the National Cancer Institute is sponsoring an ongoing phase II/III trial evaluating uproleselan in newly diagnosed older patients with AML who are fit for intensive chemotherapy. We are advancing discussions with them. I look forward to sharing an update when available. While we are already a lean organization that is right-sized for taking uproleselan through these critical next steps, we have pulled a few additional budgetary levers to extend cash runway into Q1 2025. We will continue to review our budget and cash burn as we progress. I'd now like to open the lines to Q&A. Operator? Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star one one on your telephone. If your question has been answered and you wish to remove yourself from the queue, please press star one one again. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Roger Song with Jefferies. Your line is open. Great. Thanks for the detailed analysis for phase III. Maybe a couple questions from us. The first one is, maybe to Doctor or Harout, you can add if you can all comment around. After doing such thorough analysis, what is the hypothesis for the key driver for the long OS and DUR for the primary refractory AML versus the relapse AML, either early or late? Because, you know, we should try to understand the biology behind this, you know, clinical data, similar to your earlier, other program, like, sickle cell, early onset, something. Just, curious your thoughts around the, the biology behind that. Thank you. Thank you, Roger. It's Harout here. Maybe, Ed, you can add some color on that, and then Dr. DeAngelo, feel free to add if you want. Sure. Roger, as you know, the mechanism by which uproleselan acts is to interrupt binding of AML cells to E-selectin that is constitutively expressed on bone marrow endothelial cells. Interrupting this binding leads to decreased signaling, as well as liberation of some cells, and that renders the cells more chemosensitive to chemotherapy. It may be that primary refractory disease is notably dependent on this E-selectin binding for that effect to occur. That's a hypothesis. We continue gathering data to try to understand this mechanism better. Yep. I'm happy to chime in. I think, you know, these three groups of patients are indeed very different. If you think about it, for patients who have early relapse, you know, I think the definition of relapse is changing. We know that these patients who have early relapse are still MRD positive. They've responded to the chemotherapy, but they're, they probably have a high MRD. And patients with late relapse are very similar biologically, they've just their MRD may be a little bit lower, so their relapse time is delayed. And this is in contrast to the primary refractory patients, who really have no response to chemotherapy. And so it may be that biologically, those patients, which are very, very difficult to treat, may be particularly sensitive to the mechanism of uproleselan. Got it. Yeah, that's very helpful and the rationale in terms of the biology and the mechanism. Okay, good. So maybe on the regulatory strategy, can you comment on those, how many of those analysis are pre-specified? What have been the regulatory discussion around those pre-specified analysis to be able to potentially support approval? Maybe last question is, given the strong signal you see from the primary refractory population, if FDA say this can be an interesting population, but maybe you run another small trial to validate that signal, what will be your response to that? Thank you. Thank you, Roger. Maybe I'll take the last part of your question, and then Ed can answer regarding what is pre-specified over there in the data. So I mean, obviously, we haven't had the conversation. We look forward to having a conversation with the regulators. And as you have seen, you know, we, we're talking and we're focusing on the primary refractory, but we see multiple bright spots in this patient population, which is very difficult to treat, as both Dr. DeAngelo and Dr. Rock have covered from that perspective. Regarding a potential path forward, obviously, we can't speculate and talk on behalf of the agency. What we do know is this is a very difficult-to-treat patient population. We know, especially in the primary refractory, there really aren't any options. Chemotherapy continues to stay the course, and and transplantation is the only curative approach. We're showing data over here that really is quite impressive, in terms of median overall survival of, you know, 30 months versus, you know, 10, 10, 12 months. And we look forward to, to really discussing these things. But, maybe, Ed, you can chime in on the what's pre-specified, just to make sure that, folks on this call are, are clear. Roger, as you know, the primary analysis of this trial was based on the intent to treat population of patients randomized. It was not powered for analysis of subgroups. Many subgroups were pre-specified for analysis, including primary refractory disease. And what we see is, in primary refractory disease, high unmet need, a substantial survival effect, consistency with secondary endpoints, and remarkably benign safety of uproleselan in this population. So that's the story we will share with the regulators and seek their feedback. Other areas were pre-specified as well, the backbone, as we said, and there's a clear difference of how much more uproleselan is helping patients who were on FAI, for example. So all these would be discussed in the holistic package, Roger. Got it. Thank you. Thank you. Thank you. Our next question comes from Ed White with H.C. Wainwright. Your line is open. Good morning, thanks for taking my questions. So just wanna think about this on a commercial basis. If the FDA says you have to run further trials, what were your learnings from this study that makes it financially feasible to go after a certain subgroup in future studies? In other words, what kind of investment over time and money would make it, you know... Would you get a good return on investment for the different subgroups that you've seen positive data in? Yeah. Thanks, Ed. Maybe a couple of things about that. I mean, in one of the slides, we've shown up to 40% of patients, AML patients, are primary refractory patients, from the frontline. They unfortunately do not respond to chemotherapy, as shown in that meta-analysis of 9,000 patients. If they don't respond, then the outlook is very dismal. So the unmet medical need is very high. The differences in median overall survival are quite meaningful. So, you know, we believe that, given the opportunity to serve those patients through a regulatory pathway, the uptake can be quite encouraging, given the high unmet medical need, from that side. We know that also that's a group that is 128 patients, so it's almost one-third of our patient population, so it's not an insignificant number of patients. As you know, many AML trial run, you know, what is a subset for us that can be the entire trial for some other therapy. So it is a quite a meaningful size. And as you know, Ed, we have another trial. There is another trial ongoing with the NCI in the upfront setting as well, so that can be also encouraging. Obviously, we're blinded, we don't know what's going on over there, but we're also encouraged by what we're seeing here, and hopefully that translates into the frontline setting as well, where there's less and less chemotherapy lines that have been exposed to the patient. So stay tuned. We're gonna be unfolding all this as days go by. But ultimately, our focus now is to get this very meaningful data in front of regulators and have a constructive dialogue for the sake of patients. Okay, thanks, Harout. And just a follow-up question, when you mentioned your cash runway, does that include any additional studies outside of the, NCI study currently being run? Brian, do you want to take that? No, Ed, it doesn't. No other additional studies right now in that budgeted number. Thank you. Thanks, Ed. Our next question comes from Naureen Quibria with Capital One Securities. Your line is open. Hi, good morning. I guess my first question is kind of basic, either to the team or to Dr. DeAngelo. Do you have any idea why the standard of care, the backbone therapy, performed so well in this study? Maybe Ed, and then Dr. DeAngelo, any comments? One feature is the high transplant rate of 52% in the uproleselan group, and 51% in the placebo group. Dr. DeAngelo, do you have anything to add? No, I think, you know, the hallmark of relapsed refractory leukemia is to try and get patients to transplant, and I think one of the things that we've done in all the institutions is really try and facilitate that. As you can see, some of the subgroup analysis and patients who never got to transplant, those patients did particularly poor. So we think that that really improved the outcomes from what would've been expected, as a whole. Okay, great. And then in terms of, you know, in the presentation, you said that there were no known DDIs. So why do you think with the upro combination with MEC behaved poorly, whereas combination with FAI was, you know, well, you know? So and how often is MEC used, actually? Well, I can take that. Dr. DeAngelo. So, uh- Yeah. Yeah, MEC is, MEC is primarily, was primarily used in the United States for whatever reason, whereas FAI was used elsewhere, but, you know, not entirely. It's interesting, you know, it was investigator choice. And, you know, 50, exactly 50% of patients received either backbone. You know, I think, you know, I, I struggle with this, and I think it's gonna take a deeper dive to look at the balance. Remember, patients were stratified upfront between the chemotherapy backbone. So we need to see what the, what the differences were. There were geographic differences, but what are the differences in terms of the, the patient demographics, disease characteristics, prior therapies, so on and so forth, to really understand that. I don't have a good gestalt. I'm not sure if Ed has anything else to add. That's exactly where we're looking into the data further. Okay, great. That's helpful. Maybe just one more, just out of curiosity, maybe I missed it. You know, have you reached out to the regulators? Do you have a timeframe when, you know, you'll have a discussion with them for a path forward? Yeah. So we have asked for a meeting, Naureen, and, you know, once we know more and once we have those conversations, we'll update the market appropriately. But at this point, what we're saying is we look forward to the conversation, and we have asked for a meeting. Okay, great. Thank you so much. Thank you. Again, ladies and gentlemen, if you have a question or a comment at this time, please press star one one on your telephone. I'm not showing any further questions this time. I'd like to turn the call back over to Harout for any closing remarks. Thank you, operator, and thank you for everyone for joining us on this call today. We're very excited about what we presented and look forward to updating you as we progress. Thank you very much, and this concludes our call. This concludes today's call. You may now disconnect and have a wonderful day.