GlycoMimetics, Inc.

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. At that time, lines will be open for you. If anyone should require operator assistance, please press star, then zero on your touchtone telephone. I would now like to turn the call over to Christian Deneen 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 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 Glycomimedics are Haroun Samarjan, 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, Uber-Lessolan, or our other pipeline programs, along with statements about the conduct of and our collaborators' clinical trials, plans 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. Glycomimedics 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 Haru.

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 three uprolacilam study that will enable us to report top-line results by the end of Q2 2024. Second, we continue to broaden our clinical development strategy for uprolacilam 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 III study of rupalacilam for relapsed and refractory acute myeloid leukemia. This amendment adds a time-based analysis option that will enable us to announce top-line results by the end of Q2 2024. Final analysis will evaluate effects of rupalacilam on 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 received 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 delivery of Placilan to relapse 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 Euplaceran 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 euplaciran for pediatric patients. The FDA agreed to our proposed Initial Pediatric Study Plan, or IPSP, establishing a regulatory path forward to study euplaciran as a therapeutic option for pediatric AML patients. The NCI notified us that they will initiate a Phase I-II dose escalation study to investigate safety and early activity of buprolacillin plus salvage therapy for relapsed and refractory pediatric AML. And finally, in June, the first pediatric patient was treated in an investigator-initiated Phase I-II study of buprolacillin plus a pre-transplant regimen for AML treatment. This important milestone is the first step in evaluating buprolacillin in pediatric patients. The study is being led by Dr. John Horan 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 Euproxoran 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 Ia study of GMI1687 in healthy volunteers to evaluate the drug's safety, tolerability, and pharmacokinetics. GMI1687 is a second-generation E-selectin antagonist with potential uses in diverse inflammatory diseases. Our initial focus will be on sickle cell disease. GMI1687 has been shown in preclinical models to be highly subcutaneously bioavailable. and this Phase Ia 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 III 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 1687 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 now pass it on to you to share more details on our ongoing trials.

Thanks, Arut, and thanks to all of you on the line for joining our call today. Our recent protocol amendment to the Yupra-Lessolan Phase III trial in relapsed and refractory AML will allow a time-based primary analysis of overall survival. Time-based analysis will occur after a defined cutoff date if the 295 survival events originally planned for event-driven analysis are not observed by that date. As Harut 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 enrollment of the study's 388 patients in November 2021. Correspondingly, primary survival analysis of uprolessal and benefit in relapsed and refractory AML will be based on a clinically mature data set. 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 effect of 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 Upraleslan 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 uprolacilin benefit in relapsed and refractory AML. The RATIFY trial of mitostaurin In newly diagnosed FLT3 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 and ratified 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 upralesolane versus placebo. FDA in Q2 also agreed to our initial pediatric study plan, or IPSP, for upralesolane. As part of this IPSP, the National Cancer Institute will conduct a Phase I-II trial of upralesolane plus chemotherapy for pediatric patients with relapsed and refractory AML. This study is nearly open for enrollment of up to an expected 18 patients, and each patient will receive 15 doses of uprolacilin over eight days, plus fludarabine and cytarabine. This trial will assess uprolacilin safety, pharmacokinetics, and preliminary efficacy in this population. Adult and pediatric AML are expected to have similar E-Select in biology. with chemo resistance driven by AML blast binding to bone marrow endothelial cells. So we're excited to evaluate uprolacilin with the National Cancer Institute in this study. Finally, Dr. John Horan of Boston Children's Hospital is leading a new single-arm multicenter phase 1-2 trial of uprolacilin combined with pre-stem cell transplant conditioning for patients with chemotherapy-resistant AML. This investigator-sponsored trial will describe safety, tolerability, and recommended phase two dose of upralesalan plus busulfan, clofarabine, and fludarabine chemotherapy. The first patient treated in this study recently received upralesalan and is our first ever pediatric patient treated. Recent progress in pediatric development underscores our commitment to explore uprolacilin's potential to help AML patients of all ages. We're excited to expand uprolacilin's potential utility to pediatric patients and look forward to sharing more information with you as these studies advance. Now, regarding our glycomimetic study drug platform, we're proud to share that we will initiate a Phase Ia single ascending dose trial of GMI 1687 later this quarter. GMI 1687 is a potent, subcutaneously bioavailable E-selectin antagonist. This second generation glycomimetic compound has potential applications in multiple inflammatory diseases. Our initial development focus will be on interruption of sickle cell disease vaso-occlusive crises 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 nonhuman 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 Ia trial will support design of treatment regimens for multiple inflammatory disease indications. Subcutaneous GMI 1687 may enable patient self-administration at home. If successful, that would reduce need for intravenous therapy in sickle cell vaso-occlusive crises 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, GlycoMedix 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 III clinical trial of upylacilam in individuals with relapsed refractory AML, which completed enrollment 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 UPL SLM. 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 Haroun.

Thank you, Brian. So in summary, the glaucomatics 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 III study of uroplacillin, which will enable us to announce top-line results by the end of Q2 2024. Initiating research of uroplacillin in pediatric patients with the announcement of the trials led by the NCI and Dana-Farber Cancer Institute. And last, broadening our pipeline to advanced GMI 1687 to a first in human study. With a cash runway to fund operations late into fourth quarter of 2024, glycoemetics 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. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Boris Peeker of TD Cohen. Boris, your line is now open.

Thanks. This is Nick on for Boris. Thanks for taking our questions. Just a cue for me, for the Phase 2-3 NCI trial for Rho, 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, what's the plan following this Phase 1-2 trial? Will the NCI continue to run trials, or will you guys then take it after the Phase 1-2? Thanks.

Thank you, Nick. Thanks for the question. Maybe I'll start it off and then move it over to Ed. Regarding the NCI trial in the Phase 2-3, what we know is they're still consistent with what we have 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. We're not aware of anything beyond that. So what we know is that the predetermined number of events, the FS, has not been reached. So that's been also communicated to us recently. Maybe, Ed, do you want to add more color on that one and then on the pediatric plan?

Sure. Importantly, that trial's phase two analysis, which is pending, will be based on events-free survival rather than overall survival. Both of the randomized trials completed enrollment in late 2021, so both 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'll disclose that information when it's available.

Great, thank you very much.

Thanks, Nick.

One moment for our next question. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. 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 from us. The first one is regarding the Eucalyptus long, the R&R AML study, had the team take another look at the data and how did that track in your modeling? I understand now it's time-based. Have you ever did additional kind of a data look? I think on the call, you mentioned most of the saliva, they are post-transplant, so 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, you know, updates and the fact that now we have the option of the time-based analysis on top gives us, you know, 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 see the healthy volunteer data and how would that support the next step? And do you have any timing and maybe the plan, strategic plan in terms of you will take this on your own or you will seek a partner to move forward? Thank you.

Yeah, thanks. Excellent question, Roger. I mean, as you know, 1687 for folks on the phone, this cleared 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 three. 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 deep expertise, as you know, in this area in sickle cell, and bringing that expertise on our second generation eSelectant 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, you know, it's a healthy volunteer study, so I don't want to read more into it than what it is. It's really to give us the PKPD safety signals, which are really needed first step. And quite honestly, regardless of what indications we go, that single ascending dose trial in the phase 1a is very consistent and is 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 months. 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 glyco-mimetic product in a person-human study in the marketplace.

Got it. Maybe just after the single ascending dose will be the next step in the strategic plan in terms of your own versus a partner. We'll follow up with that.

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 this 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 single cell. There's an area where we've seen prophylactic measures, you know, let's say have humbling uptakes over the last few years. And on the other side of the spectrum, gene therapies, which are very exciting, I wonder, you know, how many patients would actually benefit from that. So we do believe that the The vast majority of this patient population, unfortunately, will continue to have vasoclastic crisis. And providing an option that is on demand at the start of that vasoclastic 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 those 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.

Thank you, Roger.

Operator?

We might have dropped our operator.

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

Thank you very much. And thank you to everyone for joining our call today. We look forward to keeping you updated on glycometics and seeing some of you at the 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.