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..