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Good morning, and thank you for joining the GlycoMimetics Investor and Analyst [indiscernible] Please note this event is being recorded. Today's remarks will be followed by a question-and-answer session with the management team. [Operator Instructions] I would now like to turn the conference over to Christian Dinneen-Long, Company Counsel at GlycoMimetics. Please go ahead.

Good morning. Today, we will review top line results from our Phase III study of our lead drug candidate, uproleselan. A press release was issued this morning and is 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 Investors section of the company's website. On the call today from GlycoMimetics are Harout Semerjian, Chief Executive Officer; and Dr. Edwin Rock, Chief Medical Officer. Brian Hahn, the company's Chief Financial Officer, will also be available for the question-and-answer session. 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 company's product candidate, uproleselan, and analysis of data from the company-sponsored Phase III clinical trial; the progress and timing of clinical trials being conducted by our collaborators, including expectations regarding data readout from those trials; planned or potential data presentation; regulatory and 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, risks 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 GlycoMimetics' 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. Good morning, everyone. Earlier today, we announced top line results from our pivotal Phase III study of uproleselan or placebo in combination with MEC or FAI for the treatment of relapsed/refractory acute myeloid leukemia. Unfortunately, the study did not achieve a statistical significant improvement in overall survival in the intent-to-treat population. Adverse events were consistent with known side effect profiles of the respective chemotherapies used in the study. While this is not the outcome we were hoping for with data collected from 388 patients and an unprecedented follow-up of over 3 years, there will be important learnings from this study. We are diligently and rapidly evaluating the full data set with medical, statistical and regulatory experts and we plan to share further updates as appropriate. We intend to present a comprehensive data analysis at an upcoming medical meeting and are developing a plan to discuss these data with the FDA given the significant unmet patient need. I want to take a moment to offer my sincerest gratitude to the investigators, trial sites, and most importantly, the patients and families for their dedication to this large, well-controlled randomized trial. I also want to thank the GlycoMimetics team for working tirelessly to develop uproleselan and our investors for their support. We remain dedicated to exploring uproleselan's potential in AML. As a reminder, 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 look forward to sharing results from this trial when they become available. I will now turn the call over to Ed.

Thanks, Harout. As a reminder, this study enrolled a total of 388 patients with relapsed and refractory AML across 70 sites in 9 countries and randomized them to uproleselan or placebo with both treatment groups receiving investigators' choice of either MEC or FAI chemotherapy. All patients were randomized by 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 to this Phase III randomized study of uproleselan. And a time-based analysis was triggered with the March 31 data cutoff. As Harout mentioned, our Phase III study did not meet its primary endpoint of achieving statistical significance in overall survival in the intent-to-treat population. Patients treated with uproleselan had a median overall survival of 13 months compared to 12.3 months in the placebo arm. The control group median survival of over 1 year is unprecedented in a randomized trial of therapy for relapsed and refractory AML. Also, adverse events in the uproleselan arm were consistent with known side effect profiles of the respective chemotherapies. These features make this trial scientifically important and we will analyze these data thoroughly with medical, statistical and regulatory experts to understand these results and any lessons that could potentially benefit the AML population. We look forward to sharing results of our comprehensive analysis when available. I'll now turn it back to Harout.

Thanks, Ed. We remain committed to deepening our understanding of the study through rigorous analysis, and we look forward to sharing the full data set. We're also rapidly evaluating ways to reduce our cash burn as we complete the full analysis. In the coming weeks, we expect to report back to investors regarding a revised budget. Additionally, we will share our updated plans for uproleselan as soon as reasonably possible. I'd now like to open the lines to Q&A. Operator?

[Operator Instructions] Your first question comes from Ed White with H.C. Wainwright.

So I just wanted to get your thoughts on why the study took so much longer to read out than you initially expected? And any thoughts on why, as you said, the median survival seen in the control group was unprecedented?

Yes. Thanks, Ed. I mean, as a reminder for everyone, this trial had a primary endpoint of overall survival with a predetermined number to hit. The trial was taking longer because patients continued to live longer than what we anticipated. And given the 13 months of median overall survival in the uproleselan arm, but also the 12.5 months of median overall survival in the control arm, that is probably one of the highest control arms that we are aware of in a relapsed/refractory setting. So that's what we know. Obviously, what's driving that? We -- this is where we are now running a full-on analysis across this data-rich trial to really understand additional insights. And once we have those, we plan to share them at a subsequent medical conference and also to the market as soon as we can.

Okay. And just a question on the other studies that are ongoing. Is there going to be any impact on the NCI study? Is there an ability there to take an interim look before the anticipated data readout? And then also is there any impact to Apollomics study in China?

Yes. Probably the second question there about Apollomics, it's probably better off to ask to Apollomics, our partners. We wouldn't be in a situation to comment on their trials in China. But regarding the NCI trial, as we have disclosed our last interactions in March, they still have not reached the EFS trigger at that time. And we are going to have additional conversations with the NCI team as part of our ongoing dialogue with them. And of course, in light of our data over here, we're going to have that conversation. We -- it's a different -- it's an important thing to remember, it's a different line of therapy. It's a different backbone therapy. And it's a different endpoint. So those are important things to keep in mind is, yes, the broader area is both of them are under AML, but there are different lines, as I said, different combinations and different primary endpoints for the Phase II. So we'll see once we see that data how that does today. But we don't think there's a tremendous impact or read-through from what we've seen over here, but we will know more once we actually see that data whenever that becomes available and they share as well.

Okay. Harout, my last question is just on 1687, if you can just address that study and your thoughts on strategy going forward?

Yes. 1687 is a very good asset. I mean, that is an asset that we have developed internally based on very key learnings from the previous generation. As you know, Ed, we have advanced it through IND. We've advanced it through Phase Ia. We do see that the drug candidate behaves as we wanted to. Given that we're going to be looking at our financial situation and really revising a budget, it will be too early to say what else happens over there, but it's probably we're going to be looking at ways to conserve cash and really focus on deepening our understanding of what's going on with 301 and really work closely with regulatory partners, with clinical partners and with statistical partners as a full-fledged priority at this point.

Your next question comes from the line of Tara Bancroft with TD Cowen.

Just one for me. So I'm wondering if you could discuss any sub-populations where it could be more effective? Like I know we won't know for sure until the full analysis, but if you had to postulate some potential outcomes, which types of patients do you think that this is most possible?

Thank you, Tara, for the question. Yes, I mean, to your point, look, this is only a few days. We're literally 2, 3 days in, right, from when we got the data and we have an obligation to turn it around and communicate it. So what we're communicating is really the top line. And at the same time, we're really paying tribute to -- with 388 patients and one of the longest follow-ups, we are going to have multiple different looks at it. Obviously, when it comes to subgroups, the study is not actually powered for subgroups. However, the design does include multiple stratification factors such as age, disease status, backbone therapy. So it's really important for us to first conduct this comprehensive review of the full data set so that we can really understand what are the patients that we can help, are there additional signals in there because ultimately it's all under relapsed and refractory AML patient group, Tara. And as you know, those folks are in need of new therapies. So it's our real duty to really look into it and really understand what's going on, on a sub-group level as well. And we are going to be conducting that as soon as possible.

Okay. Great. And just one quick follow-up on that. So based on your engagements with the FDA, do you think the agency would be supportive of a potential filing in a more limited population?

Yes. I wouldn't want to speculate or talk on behalf of the FDA at this point, it's just too early. But what I can say is we've had multiple, very good conversations with the agency as we were developing this trial. There are things that they've asked us to put in, which we did. And at the end of the day, this is relapsed and refractory AML. We do have fast track, breakthrough designation, orphan status for a reason because we're aligned with the FDA that those patients, relapsed and refractory AML patients, need new therapy options. So we will do our part of deepening the understanding, having those conversations, reaching out both from a regulatory perspective, from a statistical perspective, but also from a clinical perspective and make sure that we are really advancing our understanding and engaging with partners such as the FDA to further look at the data. And based on what they see and if there is a path forward, then that would be obviously good news. But it would be too early to speculate at this point.

Your next question comes from the line of Naureen Quibria with Capital One Securities.

Sorry to hear the news. I guess, I just have really one around MRD-positive/-negative patients. Do you know if MRD-positive patients proceeded on to transplant or was it just MRD-negative that went on to transplant? And are you able to comment on how many patients became MRD-negative in [indiscernible]?

Thank you, Naureen, for the question. Yes. I mean, to your point, we have such data -- rich database with this patient, MRD-negativity, transplant rates, subsequent therapies, different backbone therapies, different stages of disease, Naureen. So all these are being looked at by the team as we speak. And as we learn more and more about it, we're going to be compiling these insights and having conversations with the regulatory agencies, such as the FDA. So stay tuned. We are committed to deepening this understanding, given the rich database and given the high unmet medical need.

[indiscernible] back over to Harout for closing remarks.

Thank you, operator. Thank you, operator, and thank you for everyone for joining our call today. So stay tuned. We are committed to updating the market as soon as we can. Thank you very much for your attention.

This concludes today's conference call. Thank you for your participation, and you may now disconnect.

Good morning, and thank you for joining the GlycoMimetics Q4 and Full Year 2023 Earnings Call. At this time, all participants are in a listen-only mode. Following management's remarks, we will hold a question-and-answer session. [Operator Instructions] I would now like to turn the call over to Christian Dinneen-Long, Company Counsel at GlycoMimetics. Please go ahead.

Good morning. Today, we will review our business updates and financial results for the quarter and year ended December 31, 2023. The press release we issued this morning is available on 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 Investors section of the company's website. On the call today from GlycoMimetics are Harout Semerjian, Chief Executive Officer; Brian Hahn, Chief Financial Officer; Dr. Edwin Rock, Chief Medical Officer; and Bruce Johnson, Chief Commercial Officer. 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 company's product candidate, uproleselan and GMI-1687, the progress and timing of clinical trials being conducted by us or our collaborators including our expectations regarding data readout from those trials, planned or potential regulatory agency interactions or submissions, development plans and activities, prelaunch preparations and the company's cash position and runway. Such statements represent management's judgment and intention as of today and involve assumptions, risks 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. In 2023, we made great strides on the path towards becoming a commercial company. Building on the advances we made in 2023, I believe 2024 will be a transformational year for GlycoMimetics. In the second quarter of this year, we expect to report top line results from our Phase III trial of our lead drug candidate, uproleselan. This is a significant milestone that can fundamentally impact our company's trajectory, while potentially helping patients affected with relapsed and refractory acute myeloid leukemia to live longer. I want to thank the entire GlycoMimetics team, our shareholders, collaborators, investigators, trial sites and patients for their trust, commitment and resilience during this multiyear Phase III trial, which has now reached clinical maturity. Thanks to everyone's combined efforts, we are now very close to unblinding this pivotal trial and should the data support it, we are ready to execute next steps rapidly. Today, I would like to highlight three key strategic areas driving the transformation of GlycoMimetics. First, based on our prior alignment with the FDA, we are triggering the time-based analysis for our pivotal Phase III trial of uproleselan in relapsed and refractory AML, and expect top line results in Q2 2024. We remain encouraged by the median follow-up time, which is now well over three years, remarkably long for the relapsed and refractory population. Pending positive results, we expect to submit a new drug application in the U.S. by the end of this year. Second, we have further advanced our commercial readiness and continue to execute critical prelaunch activities, including the expansion of our commercial and medical affairs capabilities and educational disease awareness activities. And third, we completed the Phase Ia first-in-human trial for GMI-1687, a second-generation E-selectin antagonist being evaluated as an outpatient, self-administered subcutaneous therapy to potentially alleviate sickle cell vaso-occlusive events. I'm excited to share that our Phase Ia has met its primary and secondary endpoints with no dose-limiting toxicities or other safety signals. As we look ahead to 2024 and beyond, we believe GlycoMimetics is well-positioned to deliver innovative glycobiology-based medicines to patients in need of new treatment options, beginning with uproleselan. Despite recent advancements in AML therapies, there remains a significant unmet patient need, especially in terms of bending the survival curve upwards for relapsed and refractory patients. With positive pivotal data, uproleselan has the potential to prolong survival for patients with relapse and refractory AML. This initial setting has a $650 million to $850 million near-term potential market opportunity in the U.S. alone, which could more than double when considering the frontline AML market. Our important partnerships with MD Anderson, the National Cancer Institute and the Dana Farber Cancer Institute underscore uproleselan's unique mechanism of action and potential for broad utility across the AML spectrum. Now turning to our finances. Our disciplined approach focusing on targeted investments provides a current cash runway through year end 2024. This positions the company to be financed through our upcoming clinical milestones, data readout and potential NDA submission. On today's call, I'm happy to be joined by our CFO, Brian Hahn; CMO, Dr. Ed Rock; and our COO, Bruce Johnson. I'll now pass it over to Ed to share more details on our ongoing trials.

Thanks, Harout, and thank you to all on the line for joining us today. As a reminder, in June 2023, the FDA cleared addition of an optional time-based primary analysis to our Phase III randomized trial of uproleselan in relapsed and refractory AML. This trial enrolled 388 patients and has a primary endpoint of overall survival. Survival events have continued to slow over time, so we will proceed with a time based analysis after a data cutoff at the end of this month. We look forward to reporting top line results in Q2. As Harout mentioned, median follow-up for patients remaining on study will be over three years at time of analysis, remarkable in a trial of therapy for relapsed and refractory AML. Also, a majority of surviving study patients received hematopoietic cell transplantation. And at data cutoff, a large majority of these patients will be at least two years post-transplant. That's a notable milestone, because after two years post-transplant, disease relapse becomes infrequent. Thus, these Phase III clinical trial data are clinically mature and support performance of time-based primary analysis next quarter. Our trial is testing two hypotheses. First, adjunctive uproleselan leads to deeper, more durable measurable residual disease negative responses to therapy. And second, these deeper responses and reduced gastrointestinal toxicity enable more patients to get to and through potentially curative hematopoietic cell transplantation. Rather than target a specific gene mutation, uproleselan is designed to be agnostic to cytogenetics, gene mutation profile and backbone therapy. Consistent with its molecular structure that mimics a natural complex carbohydrate, uproleselan demonstrates an unremarkable toxicity profile in trials conducted to date. So we see potential for broad uproleselan utility in combination with diverse other AML treatments across lines of therapy. Correspondingly, uproleselan potential outside of relapsed and refractory AML is under study in multiple ongoing investigator initiated trials across AML subtypes and lines of therapy. The largest of these trials is an adaptive NCI sponsored Phase II/III trial conducted by the Alliance for Clinical Trials in Oncology. This NCI alliance study is testing uproleselan in newly diagnosed older patients with AML, who are fit for intensive chemotherapy. The Phase II portion has a primary endpoint of event free survival, or EFS, and completed enrollment of 267 patients in December 2021. Just this month, NCI confirmed that the Phase II EFS event trigger has not yet been reached. This trial was designed to show median EFS prolongation from seven to 11 months, hence was expected to reach a Phase II event trigger in 2022. We look forward to sharing trial results when available. As part of our collaboration, the NCI also supports an ongoing Children's Oncology Group Phase I study conducted by COGS Pediatric Early Phase Clinical Trial Network. This dose escalation trial, which is part of the initial pediatric study plan agreed on with the FDA and EMA, assesses safety, pharmacokinetics and preliminary clinical activity of uproleselan plus chemotherapy in pediatric patients with relapsed or refractory AML. Enrollment in this study is ongoing after first patient-in occurred last October. Additional ongoing investigator initiated trials continue to evaluate uproleselan combinations in AML. These trials include uproleselan combinations with a conditioning regimen in patients up to 39 years old undergoing transplantation as well as with Azacitidine and Venetoclax in elderly patients with frontline AML. In addition, a uproleselan combination with low dose cytarabine and cladribine in patients with treated and secondary AML was recently updated at the 2023 ASH meeting. In this notoriously difficult-to-treat population, all of whom had adverse cytogenetics and were previously treated with a hypomethylating agent, cladribine, cytarabine and uproleselan led to marrow blast reductions in 72% of 18 evaluable patients. The authors concluded that this combination provides a safe approach to marrow blast reduction and disease control in preparation for potential hematopoietic cell transplantation. In summary, we believe uproleselan has broad potential utility across AML by targeting a novel form of chemo resistance from AML cell binding in bone marrow. Uproleselan's favorable safety profile makes it a good candidate for combinations with other AML therapies. Finally, both of the two large ongoing randomized trials have seen slow event accumulation and that fact highlights potential for uproleselan to become a valuable addition to diverse existing AML therapies. Beyond uproleselan, we recently completed our Phase Ia single ascending dose trial of subcutaneous GMI-1687. We will evaluate this second-generation E-selectin antagonist as an outpatient, self-administered subcutaneous therapy to potentially alleviate sickle cell vaso-occlusive events at time of pain onset. In addition to benefit from pain control, such a point of care therapy may also reduce patient emergency room visits and hospitalizations. Phase Ia first-in-human data in healthy volunteers support safety and fixed dose administration of subcutaneous GMI-1687. Full study results will be presented at an upcoming medical meeting. Also, we're pleased to announce that we've initiated a collaboration with the sickle cell disease clinical trials network of the American Society of Hematology Research Collaborative. Through this relationship, GlycoMimetics will obtain feedback from experts and people living with sickle cell disease on our GMI-1687 clinical development plan. The ASH research collaborative fosters partnerships to expedite therapeutics development, generate high quality evidence for clinical decision making and improved outcomes for people living with sickle cell disease. We look forward to our partnership with them. Now I'll turn it over to Bruce to discuss the potential commercial opportunity pending positive results of our Phase III trial.

Thank you, Ed. From a commercial perspective, there are a number of key factors that could position uproleselan for success if approved. As Harout mentioned earlier on the call, despite recent advancements in leukemia treatment, there remains a significant unmet need in AML. Currently, this disease has a low survival rate in hematologic malignancies with a five-year survival rate of around 30%. The outcomes are progressively worse for elderly AML patients who have a 15% five-year overall survival rate and for relapsed/refractory AML patients, who have a 10% five-year overall survival rate. Additionally, the vast majority of AML patients have no actionable mutation and therefore are not candidates for commercially available biomarker-driven therapies. For relapsed and refractory AML patients, in particular, outcomes remain dismal, and there's currently no standard of care regimen for patients, who are eligible for intensive therapy. Thus, novel new treatment options that are complementary to existing standard therapy with little to no additive toxicity and are agnostic to mutation profile, cytogenetic risk and treatment backbone are desperately needed. Today, hematopoietic cell transplantation remains the only treatment option with curative potential. It has become increasingly clear that MRD negative status prior to hematopoietic cell transplantation is a strong predictor of lower relapse rates and longer-term survival post-transplant. Therefore, we have designed uproleselan as an adjunct to standard therapy with the goal of achieving deeper, more durable MRD negative remissions without additive toxicity, delivering more AML patients to and through a potentially curative hematopoietic cell transplantation. Uproleselan has an unremarkable toxicity profile with no known drug-drug interactions, no pre-medications, no dose limiting toxicity, no QT prolongation or differentiation syndrome. It has been developed to be administered as a simple 20-minute IV infusion. We believe these features will provide a strong market advantage and potentially allow us to rapidly establish uproleselan as an important component of standard therapy across a variety of AML subtypes and lines of therapy. We have been building focused market access strategies that complement our medical affairs capabilities, external partnerships and teams to be ready to launch uproleselan should our pivotal study read out positively. We are fortunate to have a critical mass of team members with long-term connectivity with the hem/onc community with multiple successful launch experiences, including in AML. According to estimates from the American Cancer Society, in 2024, there will be more than 20,000 new cases of AML and more than 11,000 people will die from AML. Disease relapse and unresponsiveness to standard therapy remain a significant problem, with relapse rates of 50% to 60% after initial treatment. We estimate that the relapse and refractory addressable market is a growing population with more than 8,000 patients per year and an addressable market opportunity of $650 million to $850 million in the U.S. alone. With its unique and differentiated profile, we believe uproleselan can become an important adjunct to standard AML therapy with the opportunity to be developed for future expansion into other settings, including frontline given if the potential to access a large and growing share of the over $4 billion U.S. market opportunity across the AML treatment continuum. Now I'll turn it over to Brian for a review of financial results.

Thank you, Bruce. As of December 31, 2023, GlycoMimetics had cash and cash equivalents of $41.8 million as compared to $47.9 million as of December 31, 2022. This increase was due to the company's ability to raise additional cash early in the year. The company's research and development expenses decreased to $5.3 million for the quarter ended December 31, 2023 as compared to $5.9 million for the fourth quarter of 2022. Research and development expenses for year ended December 31, 2023 decreased to $20.1 million as compared to $28.4 million in the prior year. These decreases were due to the lower clinical development expenses related to our ongoing global Phase III clinical trial of uproleselan in individuals with relapsed/refractory AML and decreased manufacturing cost due to completion of engineering and validation batches for uproleselan, partially offset with the completion of the Phase I clinical trial for GMI-1687. The company's general and administrative expenses decreased to $4.3 million for the quarter ended December 31, 2023 as compared to $4.7 million for the fourth quarter of 2022. General and administrative expenses for the year ended December 31, 2023 increased to $19.2 million as compared to $19.1 million in the prior year. These increases were due to higher personnel related expenses, offset by a decrease in external consulting expenses. I'd now like to turn the call back to Harout.

Thank you, Brian. In closing, it has been a long road and we now have reached a very exciting time for our company. We are focused on the upcoming top line results from our Phase III study of uproleselan in relapsed and refractory AML. We continue to work on our commercial readiness and are prepared to transition into a commercial stage company pending positive results. I'd now like to open the lines to Q&A. Operator?

Thank you. [Operator Instructions] Our first question comes from Tara Bancroft with TD Cowen. Your line is open.

Hi. Good morning. So my first question is, whether you believe the frontline results could be available in time to potentially be included together with the relapsed/refractory data and a filing, or what's the plan for that? And then, next if the Phase III that you're running is successful, can you describe how you think upro will be used initially and how that could expand over time? Like, which patients are the low-hanging fruit? Does it include those with mutations or will those be added over time? Thanks.

Thank you, Tara. Good morning. Maybe I'll turn it over to Bruce to address the second question about the potential sequence, Bruce, and then, I'll take the first question. Go ahead, Bruce.

Sure, and thank you for the question. I think initially, assuming positive results from the relapsed/refractory pivotal trial, we see uproleselan quickly being established as an adjunct to standard of care with patients receiving intensive chemotherapy. We know there are a number of large volume AML centers of excellence that treat patients with intensive therapy. And those would include patients with mutations. Remember, this is a therapy that is essentially agnostic to mutational profile, cytogenetic profile and treatment backbone. So we envision broad utilization initially with patients who are fit for intensive therapy. Beyond that, of course, we have ongoing trials, ISTs evaluating the unfit population and we'll wait for further data to read out on those.

Thank you, Bruce. And regarding your first question, Tara for the regulatory pathway with the NCI-led frontline trial. So as you just heard, we have iterated that we've had conversations with the NCI. And they have confirmed that they have not reached the EFS trigger yet, which is getting quite unusual given the last patient in. And that trial was in December 2021 with an EFS trigger rather than an overall survival trigger, which is our case. So we kind of have to wait for that data until that happens. And of course, as you know, the Phase II/III adaptive trial in the frontline setting is a registrational-grade trial. So depending on the timing and depending on the data, we will have that ability to either connect them together or have them separately. We can't make that assessment now given how much delay there has been. Whenever that time data comes, we're going to be ready either do an sNDA or have that to be a separate and parallel path, because – then it really opens the market to at least double the size of the relapsed/refractory. I hope I addressed your question.

Yes. You did. Thank you so much.

Thank you.

One moment for our next question. Our next question comes from Naureen Quibria with Capital One Securities. Your line is open.

Good morning. Congrats on the progress and thanks for taking my question. I'm just curious in terms of the study is now time-based. Do you have a sense of what the event number is and would you report that with the top line data? And then, how quickly from the data cut off, which will be this month, will you be able to clean it up and report the top line? I guess what I'm asking is, will you release it towards the end of 2Q or could it be slightly earlier?

Yeah. Thank you, Naureen for the question. Yeah. We get asked that quite a bit, as you can imagine. Yeah. I mean, what we've said is, we've seen a significant reduction in the number of events over multiple stages, which led us over end '22 throughout '23 to go back to the FDA a couple of times and align with them on additional paths forward. Where we are now is, we're seeing a further slowdown of events. But given that we've aligned as of last summer with the agency on a time-based analysis, given that this database is now mature from a clinical perspective, both in terms of a median follow-up of more than three years and the fact that the vast majority of the patients who've had a transplantation have a follow-up of more than two years as well. So that really makes the database quite clinically mature and we're confident with this method of triggering it. The data cut-off, as you know, we've also mentioned end of March 31, so basically in a few days. And then we got to allow the teams the timing that it takes to do the database cleanup, database lock, the analysis that goes with it and then reporting hopefully a positive press release in Q2. So we obviously see the number of events in the back for our trial. We are blinded, but we do see the number of events and then we're very confident in this time-based analysis methodology, so stay tuned. In Q2, we hopefully will have a good press release. That's the aspiration there.

Got it. And can you share just a little bit more about this research collaboration that you have with ASH RC? So do you have any idea about the expected size of the study, when it will initiate or any other details?

Sure. Yeah. No, definitely. Before I turn it to Ed, I'm very excited about this collaboration. As you know, sickle cell patients are still in dire need for treatment, especially with our approach. And maybe, Ed, you can further expand on why we're excited with our collaboration.

Yeah. The ASH research collaborative partners with multiple sponsors to give feedback on their study drugs in sickle cell disease. The disease indication that we are going to develop, which is as a point of care method to alleviate sickle cell vaso-occlusive events, is unprecedented. And we will appreciate getting their expert feedback both from their investigators internally within the ASH research collaborative, as well as from their patient forum on our clinical development plan so that we ensure that we're keeping the patient's perspective in mind first and tapping into the expertise of leaders in this field.

Yeah. This is very exciting for us to be honest. I mean, the fact that this unmet medical need and we know this is a disease area where enrollment is difficult, enrollment takes time. And if you don't do it right from the beginning with a good collaboration, it can lead to unfortunate outcomes from a clinical trial perspective. We've learned that the hard way with our previous generation asset. And as you know, if we had stayed true to the original design of having patients be exposed to our previous generation within the first 26 hours, there was a statistically significant benefit as we reported in our post hoc and blood last year. So this time, we really want to make sure we're working hand in hand with people who are very much involved in the sickle cell community, be it on the patient level, be it on the investigator's level so that we're working together in tandem to co-create what would endpoints look like, which centers would we go so that we really are able to deliver a clinical trial that not only looks good on paper but we can actually get it done. So I'm very excited about this collaboration. And hopefully, we will report on progress in months to come.

That's helpful. Okay. Sorry, one more question, and I guess just flipping back to the Phase III study, just final one for me. Just assuming everything positive, you plan to submit everything the NDA before year-end, do you have any clinpharm or CMC (ph) studies that you still need to complete before that?

Yeah. I mean, as you know, this trial has been taking much longer than it's -- were supposed to do. So we've been really cleaning a lot of the -- what's needed being on the data side, but also on the clinpharm. Do you want to tackle the clinpharm particularly?

Yeah. Regarding clinical pharmacology, in agreement with the FDA, exposure response analysis and exposure toxicity analysis as well as population PK analysis are included in our Phase III trial and our program. This will accommodate FDA expectations and ensure that we have appropriate information for the product label to direct safe and effective use of the drug.

Thank you, Ed.

Okay. Thank you.

Thank you.

[Operator Instructions] Our next question comes from Ed White with H.C. Wainwright. Your line is open.

Good morning. Thanks for taking my questions. Perhaps I could just start with 1687. This collaboration, are there any financial stipulations in this? Does it save you money somehow? And then just if you can -- reviewing your strategy for development, does this collaboration mean you're going to go it alone? Will you be looking for a partner to further development?

Yes. Thank you, Ed. Good to hear your voice. Yes. Of course, I mean, any collaboration for it to be effective, we got to make sure that we're compensating people's time and effort. So there is a financial component for their efforts. It's modest but it's there. And regarding your second part of the question, are we going to do it alone or not, I mean, that's really an open conversation. What we would know is regardless if we're doing it alone or not, we want to advance 1687 and we want to make sure that we're learning more before we advance it and move forward into a full-on clinical development program. We want to make sure that we're very in tune with the patient voice. We're very much in tune with developing endpoints that can be delivered by physicians in the clinical trial setting, but also it's relevant for the patient. So we're gathering a lot of insights. And regardless of how we forward the execution of those insights is going to be helpful anyway. So for us, this is a no regret move with a very credible group that really is aligned with us on the sickle cell patient outcome. So that's why we're very pleased with our collaboration with them. And then those highlights will be used in due course in a clinical development setting.

Okay. Thanks, Harout. And then my other question for uproleselan is just can you give us your thoughts on your strategy for Europe, which is something you really haven't discussed all that much in the past. But since you're getting closer to a potential launch in the U.S., I think start -- it's relevant to start thinking about that and get your thoughts on that.

Yeah. No, absolutely, Ed. Those plans are ongoing. They’re underway. Our plans are not just to work with the FDA but also from a European perspective. We haven’t guided on the European side, but the work is ongoing. As you know, our clinical trial, our Phase III is half U.S. and half globally, including many sites in Europe. So we have patients over there. We have medical experts who are exposed to uproleselan and know how to use it. And of course, we’re going to be working with the European agencies as well in due time. So the first focus is on FDA, but then we should be turning our attention to Europe as well, so that’s also underway.

Okay. Great. Thanks for taking my questions.

Thank you.

And I'm showing no further questions at this time. I'd like to turn the call back over to Harout for any closing remarks.

Thank you, operator, and thank you to everyone for joining our call today. We look forward to keeping you updated on GlycoMimetics and sharing top line results in Q2. Thank you.

This concludes today's call. You may now disconnect.

Good morning, and thank you for joining the GlycoMimetics Q3 2023 Earnings Call. At this time, all participants are in a listen-only mode. Following management's remarks, we will hold a question-and-answer session. [Operator Instructions] I would now like to turn the call over to Christian Dinneen-Long, Company Counsel at GlycoMimetics. Please go ahead.

Good morning. Today, we will review our business updates and financial results for the quarter ended September 30, 2023. The press release issued this morning is available on the company's website at glycomimetics.com. This call is being recorded. 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 Investors section of the company's website. Joining me on the call today from GlycoMimetics are Harout Semerjian, Chief Executive Officer; Brian Hahn, Chief Financial Officer; and Dr. Edwin Rock, Chief Medical Officer. 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 company's product candidates, uproleselan and GMI-1687 along with statements about the progress and timing of clinical trials being conducted by us or our collaborators, planned or potential regulatory agency interactions or submissions, development plans and activities, prelaunch preparations, the company's cash position and runway and our expectations regarding data readouts from clinical trials. Such statements represent management's judgment and intention as of today and involve assumptions, risks 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. In the third quarter, we continued to make strong progress advancing our clinical pipeline as we evolve into a commercial stage organization. We remain committed to executing on our vision to deliver uproleselan to AML patients in need of new treatment options, while we leverage our unique glycobiology approach to develop innovative medicines in additional diseases such as sickle cell. Today, I would like to highlight three drivers that position us well to advance these programs in the coming year. First, we continue to expect top line results from our pivotal Phase III study of uproleselan in relapsed and refractory AML by the end of Q2 2024 and remain encouraged about the unprecedented median follow-up time. Should trial results be positive, we expect U.S. filing by end of 2024. Second, as part of our ongoing commitment to evaluate utility of uproleselan across AML, researchers from MD Anderson will present updated clinical data from their investigator-initiated trial in treated secondary AML at the American Society of Hematology meeting this December. Lastly, for GMI-1687 and our sickle cell disease program, the Phase Ia study remains on track for safety data by the end of Q1 2024. With addition of the time-based analysis option to our pivotal Phase III study of uproleselan in relapsed and refractory AML, we expect to report top line results by the end of Q2 2024. We look forward to unveiling these data at this important milestone for patients, investigators and the company. While recently FDA-approved drugs have shown encouraging results in limited AML subpopulations, we're optimistic that uproleselan has the potential to improve patient outcomes irrespective of mutation profile, cytogenetic risk or treatment backbone. Building on the promise of uproleselan in relapsed and refractory AML, we are excited to explore its broader potential across different age groups and disease settings through studies run by partners and independent investigators. For example, at the upcoming ASH Annual Meeting in San Diego, researchers from the MD Anderson Cancer Center will present updated clinical data from their Phase Ib/II study evaluating uproleselan run with cladribine and low-dose cytarabine in treated secondary AML patients. We are grateful to be collaborating with leading organizations, including MD Anderson, the National Cancer Institute and the Dana Farber Cancer Institute. The commitment of our partners underscores uproleselan's potential to improve and prolong lives for a broad spectrum of AML patients. We look forward to providing updates as these investigator-initiated clinical trials continue. Finally, we expect to announce safety data from our Phase Ia study of GMI-1687 by end of Q1 2024. We expect these data will advance us towards our aspiration to develop GMI-1687 as a patient-controlled point-of-care therapy to interrupt early sickle cell pain crisis before need to seek emergency care, we will evaluate next steps shortly thereafter. As our clinical pipeline has progressed, we have strategically expanded our commercial and medical affairs capabilities, and we are now executing critical prelaunch activities ahead of top line uproleselan readouts expected in Q2 2024. Our educational disease awareness activities target academic and community hematologists that care for AML patients. Recently, we welcomed Dr. Gaetano Bonifacio as our Vice President of Global Medical Affairs; and Debora Peralta as our Vice President of Commercial Operations. Gaetano and Deborah brings decades of hematology launch experience and we are pleased to have the opportunity to leverage their expertise during this transformative point in our company's evolution. Now turning to our finances. We have a cash runway to fund operations into late Q4 2024, allowing us to continue executing our clinical development plan. On today's call, I'm happy to be joined by our CFO, Brian Hahn; and our CMO, Dr. Ed Rock. I'll now pass it over to Ed to share more details on our ongoing trials.

Thanks, Harout. And thanks to all of you on the line for joining our call today. As Harout mentioned, we expect to report top line results of our Phase III trial by the end of Q2 2024. At that time, we'll have a clinically mature data set for time-based primary analysis of overall survival if the 295 survival events that trigger primary analysis are not already reached by that time. Median follow-up for our Phase III trial of uproleselan in relapsed and refractory AML stands now at 33-months and will be greater than three years at time of primary analysis, that's unprecedented for a therapeutic trial in relapsed and refractory AML. Also, a substantial majority of surviving study patients received hematopoietic cell transplantation and a primary analysis, a large majority of them will be at least two years out from their transplant. After two years post-transplant, disease relapse becomes infrequent. So with at least two years of post-transplant follow-up for almost all transplant recipients, we're confident that our time-based primary analysis will provide adequate trial duration to demonstrate uproleselan benefit if present. Our biologic hypothesis is that adjunctive uproleselan will lead to deeper, more durable AML disease responses that help more people to and through potentially curative hematopoietic cell transplantation. This effect may occur irrespective of specific gene mutations cytogenetic risk or treatment backbone. Correspondingly, uproleselan clinical activity is seen in both newly diagnosed and relapsed and refractory AML. Importantly, uproleselan appears to generate a notably unremarkable safety profile, adding no additional toxicity when combined with other therapies. So we are optimistic that uproleselan may one day be safely combined with diverse other therapies that are broadly useful for most or all AML patients. Partner and independent investigator studies are further exploring potential benefit of uproleselan across AML subtypes. Most importantly, a randomized NCI Phase II/III trial conducted by the Alliance for Clinical Trials in Oncology is evaluating uproleselan in newly diagnosed older patients with AML who are fit for intensive chemotherapy. This trial completed Phase II randomization of 267 patients in December 2021. Phase II analysis of event-free survival has been pending since then, now almost two years since enrollment completion. And NCI recently confirmed to us that the event trigger for analysis hasn't yet been reached. For reference, the Phase II portion of this trial was designed to demonstrate prolongation of median event-free survival from seven to 11 months. We look forward to learning Phase II results when available. Significantly, NCI expanded our collaboration and now also supports a children's oncology group Phase I study conducted by their Pediatric Early Phase Clinical Trial Network. This dose escalation trial will assess safety, pharmacokinetics and preliminary clinical activity of uproleselan plus chemotherapy in pediatric patients with relapsed or refractory AML. We're glad to announce that the first patient enrolled to this study in October. Another investigator-initiated trial led by Dr. John Horan from the Dana Farber Cancer Institute and Boston Children's Hospital also dosed its first patient earlier this year. Dr. Horan's trial is evaluating uproleselan with a pre-transplant regimen for pediatric and adult AML patients up to 39-years old. Today, we announced that at ASH in December, researchers from MD Anderson Cancer Center will present updated trial data on uproleselan in treated secondary AML. This rare, very high-risk study population is defined by prior chemotherapy treatment of an antecedent hematologic disorder. Prognosis is abysmal with expected median survival of less than five months. In the trial at MD Anderson, investigators sought to generate a safe approach to marrow blast reduction, disease control and potential for transplant by combining uproleselan with low-intensity chemotherapy of cladribine and cytarabine. Banned prognostic features in the study population include adverse cytogenetic risk and prior hypomethylating agent use in all evaluable patients and prior hematopoietic cell transplantation in 25% of them. Among 18 evaluable patients as of data cutoff, there were minimal therapy-related toxicities, 72% showed a reduction in bone marrow blasts and one patient had a potentially curative transplant. These results in this notoriously difficult to treat disease underscore broad potential utility of uproleselan across the AML spectrum. In addition, researchers from Washington University will present at ASH safety and signal generating data from their trial of uproleselan to reduce GI toxicities of melphalan chemotherapy given before transplant for multiple myeloma. Beyond uproleselan, we also made progress in our Phase Ia single ascending dose trial of GMI-1687, a second-generation E-selectin antagonist. We will evaluate GMI-1687 as a potential outpatient, self-administered subcutaneous therapy to interrupt sickle cell vaso-occlusive crises. E-selectin plays a key mechanistic role in early progression of such acutely painful pathologic events. And if successful, GMI-1687 offers potential for a point of care patient-controlled treatment option at time of pain onset. In addition to patient benefit from pain control, such a point of care therapy has potential to reduce emergency room visits and hospitalizations of recipients. As mentioned, we expect to have safety data in hand from this healthy volunteer study by the end of Q1 2024. Now I'll turn it over to Brian for a review of financial results.

Thank you, Ed. As of September 30, 2023, GlycoMimetics had cash and cash equivalents of $49.4 million, as compared to $47.9 million as of December 31, 2022. This increase was due to the company's ability to raise additional cash earlier this year. The company's research and development expenses were $5.3 million for the quarter ended September 30, 2023, as compared to $4.9 million for the same period in 2022. The increased expenses were primarily due to the clinical development costs related to the Phase Ia trial of GMI-1687 in healthy adult volunteers, which was initiated in August 2023 partially offset by decreased personnel-related and stock-based compensation costs due to lower head count. The company's general and administrative expenses increased to $4.5 million for the quarter ended September 30, 2023, as compared to $3.8 million for the same period in 2022. Increased expenses were primarily due to higher personnel-related expenses and higher professional fees as the company advances uproleselan and prepare us for potential regulatory filing and commercialization. I'd now like to turn the call back to Harout.

Thank you, Brian. In summary, we are at a crucial stage in our company's evolution. In the coming months, we will remain laser-focused on delivering the data, our Phase III study of uproleselan in relapsed and refractory AML. And continuing strategic prelaunch activities to accelerate our transition to a commercial stage company after top line results by end of Q2 2024. We have the right team with the right experience in place. And I'm confident that we will be able to build upon our collective track record of successful commercial launches should data permit. Also, we continue to explore uproleselan's potential across the AML spectrum, thanks to studies conducted by institutions such as the NCI, Dana-Farber Cancer Institute and MD Anderson Cancer Center. Finally, we continue to progress our Phase I study of GMI-1687 towards initial data readout in Q1 2024. In closing, I want to thank our employees whose hard work and dedication drive uproleselan forward as well as the patients and investigators that make these trials possible. I'd now like to open the lines to Q&A. Operator?

[Operator Instructions] Our first question will be coming from Roger Song of Jefferies. Roger, your line is open.

Great, thank you. Thanks for the update. A couple of questions from us. One thing is, can you share with us how likely by the end of 2Q 2024, you -- the primary analysis will be event based versus the time based? Just in other words, how the event accumulation since last update?

Excellent question. So as we have mentioned over the last year, we have seen at two stages a slowdown in the number of events, which really led us to the collaboration with the FDA and the introduction of the time-based event trigger. So currently, we are monitoring this very carefully, Roger. And what's happening is a lot of the patients as we are now almost two years out from full enrollment, the follow-up, a lot of the times goes into quarterly rather than monthly. So we're evaluating that over the next couple of months, and we should know better by end of year and beyond. But currently, what we are very pleased about is either through the event-based trigger or the time-based trigger, we have a definitive cutoff by end of Q2 2024.

Excellent. I look forward to the next update. And also you guided you will submit NDA by the end of this year, by the end of 2024, if the primary analysis is positive. Just curious, any outstanding CMC or preclinical work, you still need to finish before you can file the NDA or anything else, the steps into the NDA filing?

Yes. Roger, we're in a very good shape as we have been really -- this trial, as you know, has taken longer than what any of us have anticipated driven by the fact that patients continue to live longer. Meanwhile, we have done a very good job in terms of advancing CMC conversations, making sure that we have drug, making sure that we're preparing for an NDA filing with whatever we can do before we actually see the data as we continue to be blinded to that. So we think we have the foundation for a very rapid move into an NDA filing after the data, should the data be positive. So that's why we are now in a position to say that we're going to be doing that before end of the year.

Excellent. Yes, you do have some additional time to prepare all the work, okay. Maybe just last one from us, if I can is, in terms of 1687, the healthy volunteer data by the end of 1Q next year. So how should we think about that data? What are you really looking for from the data to move forward like the dose response or biomarker? That would be helpful. Thank you.

Yes. Maybe I'll tackle some of the strategic perspective. And Ed, if you want to add a few things about what we're going to be seeing. So strategically, Roger, as you know, 1687 is our second-generation E-selectin antagonist that is subcutaneously bioavailable. And that's why we're very excited to target sickle cell disease as our next area. As you know, we have a very deep tradition in that area with our first-generation molecule. So once we see -- of course, the Phase Ia is really about safety. We want to make sure that we are doing all the building blocks to get to the next level. And depending on the data and depending on where we are as well with not just the 301, our company-sponsored trial, but also the NCI-sponsored Phase II in the frontline setting, which continues to also take longer, depending on what happens with these, we will be in a situation to say what do we want to do next and when after that. But Ed, if you want to maybe tackle what's the Phase Ia.

Sure. Roger, as you know, key information from any first-in-human trial will include safety data and pharmacokinetics, in particular, will the pharmacokinetics support achievement of a potential therapeutic level of the study drug. Based on prior GlycoMimetics experience, we're confident that GMI-1687 will perform, and we'll demonstrate that and share it when available.

Awesome. That’s great. Thanks for taking the question. That’s it from the line.

Thank you, Roger.

[Operator Instructions] Our next question will be coming from Boris Peaker of TD Cowen. Your line is open.

Great. Thanks for taking my question. First, can you remind us -- maybe I missed that, how many patients in the upro study went on to transplant and also what the dropout rate was.

Good morning, Boris. In which study?

In your study specifically. But I guess if you know them for the NCI study as well, I guess it would be helpful for both of them.

Yes. What we have announced, Boris, as you know, is that in our Phase I trial in relapsed/refractory, we had seen a 31% transplant rate. And as mentioned before, in our Phase III, we are seeing a number north of that number. We have not disclosed the exact number. What we are saying is it's north of 31%.

Got you. And the dropout rate?

Ed?

Yes. The dropout rate is 3%.

Got you. Pretty low. I guess my last question is.

It's a very low number, yes.

My last question is on the NCI study. Do you have a sense of why that's taking so long?

Yes. I mean we have our opinions, obviously, but we have to wait for the data to see what's happening. And as you know, the last patient enrolled in that trial in the Phase II population 267 patients was enrolled in December 2021. And that is an EFS primary endpoint for the Phase II. So we are very intrigued and hopeful that, that's happening because events are not reaching. And if that's the case, then that's good news to patients, obviously. So we'll see once they reach the events, we are -- we collaborate with the NCI. We continue to have dialogues with them. And they have told us that when they get to the events, they will let us know. And until now, they have not done so.

Great. Thanks for taking my questions.

Thank you, Boris.

And I'm showing no further questions at this time. I would now like to turn the call back to Harout for closing remarks.

Thank you, operator, and thank you to everyone for joining our call today. We look forward to keeping you up-to-date on GlycoMimetics and seeing some of you at the Jefferies London Healthcare Conference or at ASH in December. Thank you very much.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation. You may now disconnect.

Good morning, and thank you for joining the GlycoMimetics, Q2 2023 Earnings Call. At this time all participants are in listen-only mode. Following management's remarks, we will hold a question-and-answer session. [Operator Instructions]. I would now like to turn the call over to Christian Dinneen-Long, Company Counsel at GlycoMimetics. Please go ahead.

Good morning. Today we will review our business updates and financial results for the quarter ended June 30, 2023. The press release we issued this morning is available on the company's website at glycomimetics.com. This call is being recorded, and the 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 investors section of the company's website. Joining me on the call today from GlycoMimetics are Harout Semerjian, Chief Executive Officer Brian Hahn, Chief Financial Officer, and Dr. Edwin Rock, Chief Medical Officer. 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 company's product candidate, uproleselan, or our other pipeline programs, along with statements about the conduct of and our collaborators' clinical trials, and planned or potential regulatory agency interactions or submissions, development plans and activities, pre-commercialization preparations, the company's operations, cash position and runway, and our expectations regarding data from clinical trials. Such statements represent management's judgment and intention as of today, and involve assumptions, risks 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. Good morning, everyone. This is a transformational time for our company as we continue to advance our clinical pipeline, and to evolve ourselves into a commercial stage organization. Today, we would like to highlight three major advancements that position us well for a catalyst rich upcoming 12 months. First, the FDA cleared a protocol amendment for our Phase 3 uproleselan study that will enable us to report top line results by the end of Q2 2024. Second, we continued to broaden our clinical development strategy for uproleselan by moving forward with our pediatric development plan. And third, we plan to further expand our clinical pipeline and initiate a first-in-human Phase 1a study for GMI-1687 in the third quarter of this year. These three areas of progress each represent potential long term value drivers for our company. In June, the FDA cleared the addition of a protocol amendment to our Phase 3 study of uproleselan for relapsed and refractory acute myeloid leukemia. This amendment adds a time-based analysis option that will enable us to announce topline results by the end of Q2 2024. Final analysis will evaluate effects of uproleselan on the relapsed and refractory AML in a clinically mature database, with more than three years of median follow-up. The analysis will also incorporate at least two years of post-transplant data for a large majority of patients remaining on study, who receive stem cell transplantation. Dr. Ed Rock, our Chief Medical Officer will provide additional information on the significance of this timing later in this call. The option for time-based analysis aligns with regulatory precedent for an approved AML therapy and reflects our commitment to deliver uproleselan to relapsed and refractory AML patients in need of new therapy options as soon as possible. With top line results expected by the end of Q2 2024, we continue to pursue pre-commercialization activities, while also advancing additional pipeline programs. We're also proud to expand our uproleselan development strategy by exploring its potential in people with all ages who are living with AML. This past quarter, we achieved three key advances in the development of uproleselan for pediatric patients. The FDA agreed to our proposed initial pediatric study plan or IPSP, establishing a regulatory path forward to study uproleselan as a therapeutic option for pediatric AML patients. The NCI notified us that they will initiate a Phase 1/2 dose escalation study to investigate safety and early activity of uproleselan plus salvage therapy for relapsed and refractory pediatric AML. And finally, in June the first pediatric patient was treated in an investigator-initiated Phase 1/2 study of uproleselan across a pre-transplant regimen for AML treatment. This important milestone is the first step in evaluating uproleselan in pediatric patients. The study is being led by Dr. John Moran of the Boston Children's Hospital, and Dana Farber Cancer Institute. We're grateful that the NCI and Boston Children's Hospital teams are assessing uproleselan for treatment of pediatric AML patients. And we look forward to learning more about its potential impact in this vulnerable patient population. In the third quarter, we plan to initiate a Phase 1a study of GMI-1687 in healthy volunteers to evaluate the drug safety, tolerability, and pharmacokinetics. GMI-1687 is a second generation E-selectin antagonist with potential uses in diverse inflammatory diseases. Our initial focus will be on sickle cell disease. GMI-1687 has been shown in preclinical models to be highly subcutaneously bioavailable. And this Phase 1a study is a vital first step in its clinical development. Turning to our finances, we have a cash runway to fund operations late into the fourth quarter of 2024. So we're well-positioned to continue executing our clinical development plan. Our pivotal Phase 3 trial in the relapsed and refractory AML remains on track for a top line readout at the end of Q2 2024. And we will begin a Phase 1a study of GMI-687 in the coming weeks. On today's call, I'm happy to be joined by our CFO, Brian Hahn, and CMO, Dr. Ed Rock. Ed, I'll allow pass it on to you to share more details on our ongoing trial.

Thanks Harout. And thanks to all of you on the line for joining our call today. Our recent protocol amendment to the uproleselan Phase 3 trial in relapsed and refractory AML will allow a time-based primary analysis of overall survival. Time-based analysis will occur after a defined cut-off date, if the 295 survival events originally planned for event-driven analysis are not observed by that date. As Harout mentioned, top line results are expected by the end of Q2 2024. Median follow-up for this trial will be over three years at the time of top line analysis in Q2 2024. That's unprecedented for a therapeutic trial in relapsed and refractory AML. We completed enrolment of the study's 388 patients in November 2021. Correspondingly, primary survival analysis of uproleselan benefit in relapsed and refractory AML will be based on a clinically mature dataset. That's because a substantial majority of surviving patients on study received stem cell transplantation. And almost all these transplant recipients will have at minimum two years of post-transplant follow up at the time of analysis. As you know allogeneic stem cell transplantation is the only known curative therapy for acute myeloid leukemia. Two years post-transplant is an important milestone in that after two years the graft versus leukemia effective stem cell transplantation has had time to develop fully. As a result, incidence of AML relapse after two years post-transplant is low. And these patients may be considered cured of their AML. Risk persists in this population primarily for non-AML mortality, including from infections and graft versus host disease. Still, after two years post-transplant disease relapse becomes infrequent, and disease relapse is of course what uproleselan is intended to prevent. Accordingly, the company believes capture of survival events after Q2 2024 would provide only limited additional value for primary analysis. As a result, GlycoMimetics believes that Q2 2024 provides a clinically optimal time to confirm uproleselan benefit in relapsed and refractory AML. The RATIFY trial of Midostaurin in newly diagnosed with mutant AML patients less than 60 years of age provides a regulatory precedent for our path forward. In RATIFY as in our trial, interim analysis led to a Data Monitoring Committee recommendation to continue the study. In both trials death events slowed appreciably after interim analysis. Once it became evident in RATIFY that the planned primary endpoint events trigger might not be reached, the sponsor added a time-based final analysis. In our protocol amendment, FDA also cleared addition of landmark event-free and overall survival analyses as secondary endpoints. These unpowered metrics will provide patients and healthcare providers with clear clinically important comparisons of uproleselan versus placebo. FDA in Q2 also agreed to our initial pediatric study plan or IPSP, for uproleselan. As part of this IPSP, the National Cancer Institute will conduct a Phase 1/2 trial of uproleselan plus chemotherapy for pediatric patients with relapsed and refractory AML. This study is nearly open for enrolment of up to an expected 18 patients and each patient will receive 15 doses of uproleselan over eight days, plus fludarabine and cytarabine. This trial will assess uproleselan's safety pharmacokinetics and preliminary efficacy in this population. Adult and pediatric AML are expected to have similar E-selectin biology with chemo resistance driven by AML blast binding to bone marrow endothelial cells. So we're excited to evaluate uproleselan with the National Cancer Institute in this study. Finally, Dr. John Horan of Boston Children's Hospital is leading a new single arm multi-center Phase 1/2 trial of uproleselan combined with pre-stem cell transplant conditioning for patients with chemotherapy resistant AML. This investigator sponsored trial will describe safety, tolerability, and recommend Phase 2 dose of uproleselan plus Busulfan [ph], cytarabine and fludarabine been chemotherapy. The first patient treated in this study recently received uproleselan and is our first ever pediatric patient treated. Recent progress in pediatric development underscores our commitment to explore uproleselan's potential to help AML patients of all ages. We're excited to expand uproleselan's potential utility to pediatric patients and look forward to sharing more information with you as these studies advance. Now regarding our GlycoMimetics study drug platform, we're proud to share that we will initiate a Phase 1a single ascending dose trial of GMI-1687 later this quarter. GMI-1687 is a potent subcutaneously bioavailable E-selectin antagonist. This second generation GlycoMimetics compound has potential applications in multiple inflammatory diseases. Our initial development focus will be on interruption of sickle cell disease Vaso-Occlusive Crisis, since E-selectin appears to play a major role in pathology of these acute painful episodes. Proof of mechanism preclinical studies show attenuation of VOCs by GMI-1687 in two separate mouse models of sickle cell disease. Studies in non-human primates confirm its high subcutaneous bioavailability. Our first-in-human single dose trial will assess GMI-1687 safety tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers. PK and PD data from this Phase 1a trial will support design of treatment regimen for multiple inflammatory disease indications. Subcutaneous GMI-1687 may enable patient self-administration at home. If successful, that would reduce need for intravenous therapy and sickle cell Vaso-Occlusive Crisis and provide a patient-controlled point-of-care treatment option available at pain crisis onset. Thus GMI may uniquely offer a differentiated approach with potential to interrupt Vaso-Occlusive Crisis events at time of onset. Now I'll turn it over to Brian for a review of financial results.

Thank you Ed. As of June 30, 2023, GlycoMimetics had cash and cash equivalents of $58 million as compared to $47.9 million as of December 31, 2022. The company's research and development expenses were $4.1 million for the quarter ended June 30, 2023, as compared to $8 million for the same period in 2022. The decreased expenses were primarily due to lower clinical trial and development costs related to our global Phase 3 clinical trial of uproleselan in individuals with relapsed refractory AML, which completed enrolment in November 2021. The company's general administrative expenses decreased to $4.9 million for the quarter ended June 30, 2023, as compared to $5.5 million for the same period in 2022. The reduction was primarily due to lower outside consulting and professional expenses, partially offset by commercial readiness planning expenses for uproleselan. Given that we now have definitive timing for our data readout by the end of second quarter 2024, we will be able to utilize budget contingencies to advance the first-in-human study of GMI-1687, while maintaining our anticipated cash burn of roughly $10 million per quarter, with cash runway into late fourth quarter 2024. I'd now like to turn the call back to Harout.

Thank you, Brian. So in summary, the GlycoMimetics team continues to execute on our plan. Together, we achieved multiple milestones in the last quarter that can drive long term value for our organization, including reaching an agreement with FDA to add the option of a time-based analysis to our Phase 3 study of uproleselan, which will enable us to announce top line results by the end of Q2 2024, initiating research of uproleselan in pediatric patients with the announcement of the trials led by the NCI and Dana Farber Cancer Institute. And last broadening our pipeline to advance GMI-1687 to a first-in-human study. With a cash runway to fund operations late into fourth quarter of 2024 GlycoMimetics is well positioned for a catalyst rich next 12 months. I look forward to sharing more updates on future calls. I'd now like to open the lines to Q&A. Operator.

Thank you. [Operator Instructions] Our first question comes from the line of Boris Peaker of TD Cohen. Boris Your line is now open.

Thanks. This is Nick on for Boris. Thanks for taking our questions. Just two for me. For the Phase 2/3 upro NCI trial, will they also be running a time-based analysis similar to what you guys are running for your Phase 3 trial? Or are they still keeping with their original plan for their analysis? And then also, just like a separate question, but for the pediatric patients for upro what's the plan following this Phase 1/2 trial? Will the NCI continue to run trials? Or will you guys don't then take it after the Phase 1/2? Thanks.

Thank you, Nick. Thanks for the question. Maybe I'll start it off and then hand -- move it over to Ed. Regarding the NCI trial and the Phase 2/3 what we know is they're still on -- consistent with what we've communicated last quarter, is that they have not reached their events. So I think we're going to have to wait for that and see where they go next. They haven't -- we're not aware of anything beyond that. So what we know is that a predetermined number of events, the event has not been reached. So that's been also communicated to us recently. Maybe Ed, you want to add more color on that one and then on the pediatric plan.

Sure. Importantly, that trial's Phase 2 analysis which is pending will be based on events-free survival rather than overall survival. Both of the randomised trials completed enrolment in late 2021. So both have been -- have taken a good long time to mature over 18 months. We don't anticipate that the NCI will change their analytic plan to change from an event-based EFS analysis to a time based EFS analysis. And then for the second question about NCI's plans beyond the pediatric Phase 1/2, those have not yet been decided definitively and we will disclose that information when it's available.

Great, thank you very much.

Thanks, Nick.

One moment for our next question. [Operator Instructions]. And our next question comes from the line of Roger Song of Jefferies. Roger, your line is now open.

Great. Thanks for the update and taking our question. A couple of them. The first one is regarding the uproleselan, the R&R AML to the study, had the team take another look at the data. And how did that track in your modeling? Understand now it's time based but have you ever done additional kind of data look? I think on the core, you mentioned most of the survivor, their post transplant or any additional color, you can provide to us Thank you.

Yeah, thank you, Roger. Yeah, I mean, the trial continues. Patients continue to live longer in this trial. So obviously, as you know, we're blinded. We do take a look at the pooled blinded data. And we're excited that we have now this option of the time-based analysis should the 295 events not be reached by next year, we believe we're going to have a mature database, given the three years median follow-up, given the two years plus of post-transplant follow-up as well, for the vast majority of patients, that we're going to have a mature database. So things continue to be on track. Patients continue to live longer. Obviously, we don't know who's on what arm, but we're very encouraged by this updates and the fact that now we have the option of the time-based analysis on top, gives us certainty, clarity, and of course, on a database that's going to be mature.

Excellent, thank you. And regarding the 1687, so what do you expect to speed up healthy volunteer data and how would that support the next step? And do you have any timing and the maybe the plan -- strategic plan in terms of you will take this on your own or you are seeking a partner to move forward? Thank you.

Yeah, thanks. Excellent question, Roger. I mean, as you know, 1687 for folks on the phone, this is clear this other asset that we have cleared IND back in June of last year. And given where the markets were, the financial constraints we had, we really had to double down on our Phase 3. We're very excited now to be able to be in a situation where we're able to start the Phase 1a of 1687, a compound we believe in, we have the deep expertise, as you know, in this area in sickle cell, and bringing that expertise on our second generation, E-selectin antagonist, that is potent and subcutaneously bioavailable. So the first step of that, Roger, as you know, is that single ascending dose, as Ed mentioned. And really, it's a healthy volunteer study. So I don't want to read more into it, than then what it is. It's really to give us the PK/PD safety signals, which are really needed at first step. And quite honestly, regardless of what indications we go, that single ascending dose trial and the Phase 1a is very consistent and the same. So we're going to be doing this, typically these volunteer trials they don't take that much time but it's usually in the month. So sometime, I would say next year we should have that information. It's just too early to tell now. Let's get started. As we're announcing today, we are planning to start. We haven't started yet. So let's get started and we'll keep the market updated about it. But I'm very excited about the ability to start 1687 and put yet another GlycoMimetics product in a first-in-human study in the marketplace.

Got it. Yeah, maybe just to ask you the single ascending dose, that will be the next step and sticking to your plan in terms of your own versus the partner?

Yeah, I mean, it's too early to say, Roger. I mean, regardless if we're going to be doing it ourselves, or we're going to be partnering, we need this data anyway. And the fact that we're able to fund it, we're able to move it forward, it's a great, great step. As we've said multiple times, we're always open to partnership conversations, but we don't really have to. In a way the partner has to bring beyond just the cash, has to bring in that expertise, dedication to sickle cell. IT's an area where we've seen prophylactic measures, let's say have humbling updates over the last few years. And on the other side of the spectrum, gene therapies, which are very exciting. I wonder, how many patients would actually benefit from that. So we do believe that the vast majority of this patient population unfortunately will continue to have Vaso-Occlusive Crisis, and providing an option that is on demand at the start of that drive, as it was different crisis is going to be a tremendous help for this patient population. So while we hope that there's multiple different approaches, we do believe that this approach will have a market for it. But of course before getting ahead of ourselves first, let's start the single ascending dose trials. Let's get that going. Let's continue the conversations as well with people who are very motivated in doing trials in sickle cell disease. And that medical community is very active, that patient community is very active. So we look forward to partnering with them, and potentially other institutions if that works for us and for them. But meanwhile, we have gotten the ball going.

Understood. Thank you. Thank you everyone. That's it for us.

Thank you, Roger. Operator? We might have dropped our operator.

I'm back. Thank you all. I apologize. There was a slight disconnection. I believe it is time to wrap up. So we can turn it back over to Harout. We are done with questions for now. Harout, it is on for you.

Yes, thank you very much. And thank you to everyone for joining our call today. We look forward to keeping you updated on GlycoMimetics and seeing some of you at H.C. Wainwright Healthcare Conference in September.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.