Q4 2023 GlycoMimetics Inc Earnings Call
Participants
Christian Dinneen-Long; General Counsel; GlycoMimetics, Inc.
Harout Semerijian; CEO; GlycoMimetics, Inc.
Edwin Rock; CFO; GlycoMimetics, Inc.
Bruce Johnson; CCO; GlycoMimetics, Inc.
Brian Hahn; CFO; GlycoMimetics, Inc.
Tara Bancroft; Analyst; TD Cowen
Lorraine Cavari; Analyst; Capital One Inc.
Ed White; Analyst; H.C. Wainwright
Presentation
Operator
Good morning, and thank you for joining the GlycoMimetics Q4 and full year 2023 earnings call. (Operator Instructions) I would now like to turn the call over to Christian Dinneen Long company counsel at GlycoMimetics. Please go ahead.
Christian Dinneen-Long
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 the company's website at glycomimetics.com. This call is being recorded and a dial-in phone replay will be available for 24 hours after the close of the call. The webcast replay will also be available for 30 days in the Investors section of the company's website. On the call today from GlycoMimetics are Harout Semerijian, Chief Executive Officer, Brian Hahn, Chief Financial Officer, 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 candidates used for 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.
Central potential regulatory agency interactions are 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 statements. 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 Semerijian
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 our GlycoMimetics. In the second quarter of this year, we expect to report top line results from our Phase 3 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 3 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 supported, 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 3 trial of e 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 US by the end of this year.
Second, we are further advanced. 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 1a 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 Phase1a 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 glyco biology 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 pulp with positive pivotal data, your cholesterol 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 US 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 your plus lands 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 CCO. Bruce Johnson.
I'll now pass it over to Ed to share more details on our ongoing trial.
Edwin Rock
Thanks, Ruth, and thank you to all on the line for joining us today. As a reminder, in June 2023, the FDA cleared the addition of an optional time-based primary analysis to our Phase 3 randomized trial 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, the 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 3 clinical trial data are clinically mature and support performance of time-based primary analysis next quarter. Our trial is testing two hypotheses.
First, adjunctive use progressively and 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 and is designed to be agnostic to cytogenetics gene mutation profile and backbone therapy, consistent with its modular structure that mimics a natural complex carbohydrate uproleselan demonstrates an unremarkable toxicity profiles and profile and trials conducted to date.
So we see potential for broad uproleselan and utility in combination with diverse other AML treatments across lines of therapy. Correspondingly, the uproleselan potential outside of relapsed and refractory AML is under study in multiple ongoing investigator initiated trials across AML sub-types in lines of therapy. The largest of these trials is an adaptive NCI sponsored Phase 2/3 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 2 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 2 EFS event trigger has not yet been reached this trial was designed to show median EFS prolongation from 7 to 11 months, hence was expected to reach a Phase 2 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 1 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 and combinations in AML These trials include uproleselan combinations with the conditioning regimen in patients up to 39 years old undergoing transplantation as well as with Phase 1 cytarabine and cladribine in elderly patients with frontline AML.
In addition, uproleselan in combination with low-dose uproleselan 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 hypomethylating agent. Cytarabine and cladribine uproleselan led to marrow blast reduction 72% of 18 evaluable patients. The authors concluded that this combination provides safe approach to and disease control in preparation for potential hematopoietic cell transplantation reated with a hypomethylating agent, Cladribine cytarabine and Neupro vessel and led to marrow blast.
In summary, we believe uproleslan has broad potential utility across AML by targeting a novel form of chemo resistance from AML, cell binding and bone marrow uproleselan 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 1a 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 basal occlusive events 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 1a, 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 collaboration. Through this relationship, GlycoMimetics will obtain feedback from experts and people living with sickle cell disease on our GMI 1687 clinical development plan, ASH research, collaborative fosters partnerships to expedite therapeutics development, generate high-quality evidence for clinical decision making and improve 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 3 trial.
Bruce Johnson
Thank you, Ed. from a commercial perspective, there are a number of key factors that could position you for uproleselan for success, if approved, as Rob mentioned earlier on the call, despite recent advancements in leukemia treatment there remains a significant unmet need in AML. Currently, this disease has the lowest survival rate in hematologic malignancies with a 5-year survival rate of around 30%. The outcomes are progressively worse for elderly AML patients who have a 15% 5-year overall survival rate and for relapse refractory AML patients who have a 10% 5-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 therapy 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 not stick 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 you for less on 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 premedication, 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 for uproleselan should our pivotal study readout positive.
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 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 US 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 the potential to access a large and growing share of the over $4 billion US market opportunity across the AML treatment continuum.
Now I'll turn it over to Brian for a review of financial results.
Brian Hahn
Thank you, Bruce. And 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 lower clinical development expenses related to our ongoing global Phase 3 clinical trial of uproleselan individuals with relapsed refractory AML and decreased manufacturing costs due to completion of engineering and validation batches for uproleselan partially offset with the completion of the Phase 1 clinical trial for GMI-1687.
The company's general 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.
Harout Semerijian
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 3 study of restaurants in relapse 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?
Question and Answer Session
Operator
Thank you.
(Operator Instructions)
Tony Bancroft with TD Cowen.
Tara Bancroft
Hey, good morning. So my first question is weather. You believe that 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 year, if the Phase 3 that you're running is successful. Can you describe how you think Neupro will be used initially and how that could expand over time, which patients are the low-hanging fruit because it doesn't include those with mutations on FIT or will those be added over time?
Harout Semerijian
Thank you, Tara. Good morning. Maybe I'll turn it over to Bruce to address the second question about the potential sequence a boost. And then I'll take the first question.
Bruce Johnson
Sure, and thank you for the question. And I think initially, assuming positive results from the relapsed-refractory pivotal trial, we see you uproleslan 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 profiles, 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 readout on those.
Harout Semerijian
Thank you, Bruce.
And regarding your first question, tariff or the regulatory pathway with NCIL. for frontline trial. So as you just heard, we've 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 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 2/3 adaptive trial in the frontline setting is a registrational great 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 to 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 relapse refractory.
I hope I addressed your costs.
Tara Bancroft
Yes, you did. Thank you so much.
Operator
Lorraine [cavari], Capital One Securities.
Lorraine Cavari
Good morning and congrats on the progress and interesting. My question and I'm just curious in terms of, you know, the study is now time-based? And 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 a data cutoff, 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 toward the end of 2Q? Or could it be slightly earlier?
Harout Semerijian
Yes. Thank you, Lorraine, for the question. Yes, we get asked that quite a bit as you can imagine. Yes, I mean, what we've said is we've seen a significant reduction in the number of events over multiple stages, which lead us over and '22 throughout '23 to go back to the FDA a couple of times and aligned with them on on additional path forward. Where we are now is we are seeing a further slowdown of events, but given that we've aligned as of last summer with the 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 have had a transplantation have a follow-up of more than two years as well.
So that's really makes the database quite clinically mature, and we are confident with this method of triggering at. The data cutoff as you know, we've also mentioned Endo March 31. So basically in a few days and then that we got to allow the teams, the timing that it takes to do the database cleanup, you know, the 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 row for our trial and we are blinded, but we do see the number of events, and we're very confident in this time-based analysis methodology.
So stay tuned in Q2. We hopefully will have a good press release.
Lorraine Cavari
Can you share just a little bit more about this recent collaboration that you have with ash RC2? Would you have any idea about the expected size of the study when it or initiate or any any other details?
Harout Semerijian
Sure. Yes. No, that's not the I before I turn it to add. 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 on why we're excited with our collaborations.
Edwin Rock
Yes. 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 our method to alleviate sickle cell basal occlusive events is unprecedented, and we will appreciate getting their expert feedback votes from their investigators internally within the ASH research collaborators, collaborative as well as from their patient forum on our clinical development plans so that we ensure that we're sort of keeping the patient's perspective in mind first and tapping into the expertise of leaders in this field.
Harout Semerijian
Yes, this is very exciting for us. To be honest. I mean, the fact that we know 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 it can lead to unfortunate outcomes from a concept of a clinical trial perspective, we've learned that the hard way with our previous generation assets. And as you know, if we had stayed true to the original design, 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 block last year. So this time we really want to make sure we're working hand in hand with, you know, with people who are very much involved in the sickle cell community, be it on the patient level be it on the investigators level so that we're working together in tandem to co-create what would endpoints look like, which centers with 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.
Lorraine Cavari
That's helpful. Okay. Sorry, one more question. And I guess just holding back to the Phase 3 study and the final one for me and assuming everything positive you plan it and submit everything to the FDA before year end? And do you have any claim far more CNC studies going to complete before?
Harout Semerijian
Yes. I mean, as you know, this trial has been taking much longer than than it's supposed to do. So we've been really cleaning a lot of the -- the what's needed being or the data side, but also on the clin pharm.
Edwin Rock
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 three trial in 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.
Lorraine Cavari
Okay. Thank you.
Operator
(Operator Instructions)
Ed White, H.C. Wainwright.
Ed White
Thanks for taking my question. And 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 review your strategies for development this collaboration, you're going to go it alone. Will you be looking for you? Will you be looking for a partner to further development?
Harout Semerijian
Yes, thank you, Ed. Good to hear your voice?
Yes, of course, I mean, any collaboration for it to be effective. We've 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 are learning more before we advance it and move forward into a full-on clinical development program. We want to make sure that we are very in tune with the patient voice. We're very much in tune with developing endpoints that can be delivered by physicians in a clinical trial, setting it, but also it's relevant for the patient.
So we are gathering a lot of insights and regardless of how we move 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 has aligned with us on that, that would be 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 and a clinical developments.
Ed White
Okay. Thanks, Haroute. And then my other question on Insulation is just can you give us your thoughts in your strategy for Europe, which is something I really haven't discussed all that much in the past. But since you're getting closer to two potential launch in the US at the start, it's relevant to start thinking about that and get your thoughts on that?
Harout Semerijian
Yes. No, absolutely. And then yes, 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 3 is half US and half globally, including many sites in Europe. So we have patients over there. We have medical experts who are are exposed to your uproleslan and 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.
Ed White
Okay, great.
Thanks for taking my questions.
Harout Semerijian
Thank you.
Operator
And I'm showing no further questions at this time. I'd like to turn the call back over to Herbert for any closing remark.
Harout Semerijian
Thank you, operator, and thank you to everyone for joining our call today, and we look forward to keeping you updated on GlycoMimetics and sharing top line results in Q2 Thank you.
Operator
This concludes today's call. You may now disconnect.
