CBIO - NASDAQ

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.