GlycoMimetics - Q2 2023

Transcript

Operator (participant)

Good morning, 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 touch-tone telephone. I would now like to turn the call over to, Christian Dinneen-Long, Company Counsel at GlycoMimetics. Please go ahead.

Christian Dinneen-Long (General Counsel and Company Secretary)

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 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, 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. 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.

Harout Semerjian (Former CEO)

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 III Uproleselan 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 Uproleselan by moving forward with our pediatric development plan. Third, we plan to further expand our clinical pipeline and initiate a first-in-human Phase 1-A 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 Uproleselan 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 Uproleselan 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 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. Finally, in June, the first pediatric patient was treated in an investigator-initiated Phase 1/2 study of Uproleselan plus 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 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 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 1-A study of GMI-1687 in healthy volunteers to evaluate the drug's 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 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 1-A 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.

Edwin Rock (Former CMO)

Thanks, Harout, and thanks to all of you on the line for joining our call today. Our recent protocol amendment to the uproleselan 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 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 enrollment 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 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, incidents 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 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 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 enrollment 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 chemoresistance driven by AML blast binding to bone marrow endothelial cells. 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, multicenter, 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 recommended phase II dose of Uproleselan plus busulfan, clofarabine, and fludarabine 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. Regarding our glycomimetic 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 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 non-human primates confirm its high subcutaneous bioavailability. Our first-in-human single-dose trial will assess GMI-1687's safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. PK and PD data from this phase 1-A 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.

Brian Hahn (Former CFO and SVP)

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 31st, 2022. The company's research and development expenses were $4.1 million for the quarter ended June 30th, 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 Uproleselan 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 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.

Harout Semerjian (Former CEO)

Thank you, Brian. 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 III 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. 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?

Operator (participant)

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 one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one, one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Boris Peaker of TD Cowen. Boris, your line is now open.

Nicholas Lorusso (Biotech Analyst)

Thanks. This is Nick on for Boris. Thanks for taking our questions. Just two for me. For the phase 2/3 NCI trial for row, will they also be running a time-based analysis similar to what you guys are running for your phase III trial? Are they still keeping with their original plan for their analysis? Then also, just like a separate question, but for the pediatric patients, for row, 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.

Harout Semerjian (Former CEO)

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

Edwin Rock (Former CMO)

Sure. Importantly, that trial's phase II analysis, which is pending, will be based on event-free survival rather than overall survival. Both of the randomized trials completed enrollment in late 2021, so both have been, have taken a, a, 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. For the second patien- second question about NCI's plans beyond the pediatric phase I, II, those have not yet been, decided definitively, and we'll disclose that information when it's available.

Nicholas Lorusso (Biotech Analyst)

Great. Thank you very much.

Harout Semerjian (Former CEO)

Thanks, Nick.

Operator (participant)

One moment for our next question. As a reminder, to ask a question, you will need to press star one, one 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.

Roger Song (Senior Equity Research Analyst)

Great. Thanks for the update and taking our question. A couple from us. The first one is regarding the Uproleselan, the R/R AML period of study, had the team taken another look at the data, and how did that track in your modeling? I understand now it's time-based, but have you ever the additional kind of a data look? I think on the call you mentioned most of the survivor, they are post-transplant, so any additional color you can provide us, provide it to us? Thank you.

Edwin Rock (Former CMO)

Yeah. Thank you, Roger. Yeah, I mean, the, the, the trial continues. Patients continue to live longer in this trial. 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 gonna 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 gonna have a mature database. 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, 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, on a database that's gonna be mature.

Roger Song (Senior Equity Research Analyst)

Excellent. Thank you. Regarding the 1687, what do you expect to see the healthy volunteer data, and how would that support the next step? Do you have any timing and maybe the plan, strategic plan in terms of you will take this on your own or you will seeking a partner to move forward? Thank you.

Harout Semerjian (Former CEO)

Yeah, thanks. Excellent question, Roger. I mean, as you know, 1687, for folks on the phone, this, this cleared this other asset that we have cleared IND back in June of last year. Given where the markets were, the financial, you know, constraints we had, we really had to double down on our phase III. We're very excited now to be able to be in a situation where we're able to start the phase 1-A of 1687, a compound we believe in. We have deep, 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. The first step of that, Roger, as you know, is, is that single ascending dose, as Ed mentioned.

Really, you know, it's a healthy volunteer study, so I don't wanna read more into it than, than what it is. It's really to give us the PK/PD, safety, signals, which, which are really needed, as a first step. Quite honestly, regardless of what indications we go, that, that single ascending dose trial in the Phase 1-A is, is very consistent and is the same. We're gonna be doing this. Typically, these volunteer trials, they don't take that much time, but, you know, it's, it's usually in the, in the months. Sometime, I would say next year, we should have that information. It's just too early to tell now. Let, let's get started. As, as we are now as we're announcing today, we are planning to start. We haven't started yet.

Let's get started, and, we'll, we'll keep the market updated about it. 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.

Roger Song (Senior Equity Research Analyst)

Got it. Yeah. Maybe just, you know, after the single, single ascending dose, what will be the next step and strategic plan in terms of your own versus a partner? To follow up that.

Harout Semerjian (Former CEO)

Yeah, I, I mean, it, it's too early to say, Roger. I mean, regardless if we're gonna be doing it ourselves or we're gonna be partnering, we need this data anyway. The fact that we're able to fund it, we're able to, you know, move this forward, it's a great, great step. As, 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 you know, sickle cell. This is an area where we've seen prophylactic measures, you know, let's say, have humbling uptakes over the last few years.

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. 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 vaso-occlusive crisis is going to be a tremendous help for this patient population. While we hope that there's multiple different approaches, we do believe that this approach will have a market for it. Of course, you know, 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, that, that medical community is very active, that patient community is very active. We look forward to partnering with them and potentially other, other institutions if that works for us and for them. Meanwhile, we have gotten the ball going.

Roger Song (Senior Equity Research Analyst)

Understood. Thank you. Thank you, Harout. That's it on us.

Harout Semerjian (Former CEO)

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

Operator (participant)

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

Harout Semerjian (Former CEO)

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

Operator (participant)

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