GlycoMimetics, Inc.

Today's conference is scheduled to begin shortly. Please continue to stand by and thank you for your patience. Thank you. Thank you. Thank you. Thank you. Good morning, and thank you for joining the Glycomimetics call. At this time, all participants are in a listen-only mode. Following management's remarks, we will hold a question-and-answer session, and at that time, the lines will be open for you. If anyone should require operator assistance, please press star, then zero on your touchtone telephone. I would now like to turn the call over to Sharianne's group at Glycomimetics. Please go ahead.

Good morning. Today we will review our accomplishments and financial results for both the year end and the quarter ended December 31st, 2021. The press release we issued this morning is available on the company's website at www.glycomimetics.com under the Investors tab. This call is being recorded. 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 investor relations section of the company's website. Joining me on the call today from Glycomimetics are Harut Suburjan, Chief Executive Officer, Brian Hahn, Chief Financial Officer, and Armand Girard, Chief Business Officer. We will start today's call with comments from Harut. Brian will follow and provide an overview of the company's financial position. We'll then open the call for Q&A. I'd like to remind you that today's call will include forward-looking statements based on current expectations. Forward-looking statements on this call may include, but are not limited to, statements about the company's product candidates, UPALESA land, GMI 1359, GMI 1687, and our other pipeline programs. along with statements about expectations regarding our operations, cash position, and data from preclinical studies or clinical trials, as well as planned or potential future development, regulatory interactions or submissions, and potential commercialization activities or strategic collaborations. 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 Glycomimetics filings with the SEC, which are available from the SEC or on the Glycomimetics website. I'll now turn the call over to Haru.

Thank you, Sherry, and good morning, everyone. 2021 was a transformative year for glycomimetics. We advanced from a research-based company to a commercially focused organization. Our number one priority was completing enrollment of our own phase three pivotal trial, evaluating uprolaceran in relapsed refractory AML patients. Towards the end of the year, recruitment for our trial increased significantly, reaching full enrollment in November. Within two weeks of enrollment completion of our trial, the Phase II portion of the NCI's Phase II-III clinical trial in newly diagnosed AML patients also completed enrollment. Both trials exceeded their patient recruitment targets with over 650 AML patients enrolled across both studies. This was a significant achievement, particularly during a global pandemic that had negatively impacted numerous clinical studies in our industry. Looking forward, our focus is preparing for a potential submission of a new drug application and the commercialization of buprenorphine. We are diligently collecting and preparing our phase three data for analysis. Our breakthrough therapy designation provided us an opportunity to interact with the FDA on numerous occasions during 2021. Based on these interactions, we believe that our non-clinical and CMC package will support registration. You should know that we have also manufactured the registration batches of drug product to support the NDA. To further enhance our NDA readiness, we are taking additional proactive steps that extend beyond clinical operations to bolster our CMC, regulatory, medical affairs, and commercialization teams. As you know, the primary endpoint for our phase three trial of overall survival is event driven. Based on our current projections, we expect top line results to come in after year end 2022. As more events occur, our goal is to provide more precision on the timing of the top line readout. With regards to the NCI-sponsored trial, we expect to receive the interim analysis of event-free survival on the 267 patients enrolled. We will press release the data when the NCI shares its analysis with us. The results will determine the next steps for this program. whether the data could support a filing for accelerated regulatory approval, whether the phase three portion will move forward, or whether the trial will stop. In the interim analysis, if the interim analysis is compelling, the NCIS data in the newly diagnosed setting will be transferred to us for regulatory filing purposes. Externally, your proletariat is getting featured in clinical journals and expert forums. In September, the Phase 1-2 data supporting Guproletharan's potential was highlighted in the online edition of Blood. The article reported that 69% of patients achieved minimal residual disease negativity, which has been shown to be the strongest predictor for overall survival in AML. The importance of achieving CR MRD negativity was highlighted in two recent publications, one by the group at Andy Anderson Cancer Center and another at the University of Wisconsin School of Medicine. In both these publications, the authors conclude that in patients with relapsed refractory AML, CR with MRD negativity was associated with the best outcomes. patients who achieved CR with MRD negativity had the lowest rates of relapse and best two-year survival, which was driven largely by an increased ability to undergo stem cell transplant. The blood article also concluded that, first, despite over 50% of patients being classified as having high-risk leukemia, we observed a 41% CR-CRI rate with the addition of uproliferin. Of note, 35% of these responses were full CRs, which highlights the quality and depth of response. Second, 50% of patients achieving a CR-CRI went on to allogenic transplant. And finally, All of this culminated in prolonged survival, which is a great outcome for patients. Just last month, the same article was published in the journal's print edition. These data were placed in a blood expert commentary by MD Anderson experts. The authors confirmed that the results of this Phase I-II study are encouraging and expressed hope that this approach of targeting the bone marrow niche will improve clinical outcomes in the Phase III trial. We are also pleased to see the role of E-Selectin antagonism being discussed in the clinical education forums. Last month, during the DAVA Oncology Acute Leukemia Forum, this novel extrinsic approach to targeting E-Selectin-mediated chemoresistance with your proletaran was highlighted during several expert presentations. During the plenary session focused on leukemia microenvironment, presentations from three medical experts reviewed data implicating E-Selectin as a key mediator of leukemic cell drug resistance and the potential role of your proletaran in deepening remissions. Collectively, This external recognition gives us great confidence of your prolesterin's potential to positively impact the lives of AML patients. Glycometics is chartering a new approach for treating leukemia. As you recall, leukemia lives in the bone marrow. There, leukemic cells induce the expression of isolectin to promote their pro-survival pathways. and also to protect themselves from the effects of chemotherapy. If we expect to have any hope of further improving outcomes in this patient population, we must disrupt these interactions. Euprolasteran represents this new approach of disrupting extrinsic factors of chemoresistance. We believe Euprolasteran has the potential to be transformative for relapsed refractory AML patients. where a high unmet medical need still remains. In addition to these achievements, 2021 was also a year of transition for us in terms of leadership. I joined the company in August when my predecessor retired. I saw an organization with a highly novel glycobiology-based approach, a pipeline of first-in-class drug candidates, and a focus on underserved patient populations. That has significant commercial potential. After seven months on the job, I continue to be enthusiastic about your program, about the pipeline, and definitely about our people. To complement our strong team, we've added three accomplished leaders. Lisa DeLuca joined us as Vice President, Regulatory Affairs. Dr. DeLuca is a veteran regulatory expert. who has previously led the strategy formation and execution of multiple global NDA submissions and product registrations. Lisa's focus will be to advance our NDA and continue to engage the FDA and other regulatory authorities. Bruce Johnson transitioned from our commercial consultant to a senior vice president and our first chief commercial officer. Bruce has over 25 years of experience in oncology, and his near-term focus will be to develop a commercialization strategy for Eupressoram, accelerate competitive readiness, deepen medical expert engagement, and broaden scientific education. Finally, Dr. Deepak Tiwari just joined us as vice president in technical operations. Deepak brings to our leadership team over 25 years of diverse technical management, not only in CMC, but also broad experience, contributing to more than 30 regulatory submissions and 15 commercial product launches throughout his career. As we move our lead product, UproLess, around forward towards the potential submission of an NDA, as well as to develop our pipeline and research product candidates, Deepak's breadth of experience and leadership will be valuable for our team. I would now like to provide insights into five additional operational highlights from 2021. First, our collaboration with Appleomics in Greater China made significant progress during the year. In January, the team secured breakthrough therapy designation in China for uproliferin and advanced from a Phase I bridging study to a Phase III registrational trial in relapsed refractory AML. Second, we announced three investigator-sponsored trials collaborating with investigators at MD Anderson, at UC Davis, and WashU at St. Louis. All three ISTs are currently enrolling patients. Our hope is that data generated by these prestigious cancer research centers will be submitted for presentation at future scientific conferences and will pave the way for expanding the breadth of clinical use of buproliferan across AML and other hematologic malignancies. Third, as for our efforts in sickle cell disease, we accelerated the development of GMI-1687, a first-in-class subcutaneously administered E-selectin antagonist for the treatment of acute vaso-occlusive crisis. We know from the post-hoc analysis of the Phase III reset and open-label extension studies with rivipenzel that early intervention is critical to achieving clinical benefit. Clinicians have told us that an on-demand therapy, either self-administered at home or given in an outpatient ER clinical setting, could be a game changer. There remains no FDA-approved therapy for the treatment of VOC, and our goal is to submit an IND to the FDA in the first half of this year. Fourth, GMI 1359. Our dual antagonist of CXCR4 and E-Selectin was showcased in the 2021 ASH meeting in December. Our collaborators at MD Anderson highlighted the potential for GMI1359 in breaking resistance in AML, particularly in patients with FLIT3 mutations. We are exploring strategic options for this program. And fifth, we are advancing our Galectin3 program. We have nominated GMI2093 as a development lead candidate after observing high affinity, specificity, and oral bioavailability. The role of Galectin-3 in cancer, fibrosis, and other inflammatory disease is emerging as a therapeutic target, and our intent is to advance this program through potential strategic partnerships. Brian? I'll now turn it over to you to provide an overview of our financial results.

Thank you, Harut. As of December 31st, 2021, GlecmoMedx had cash and cash equivalents of $90.3 million as compared to $137 million as of December 31st, 2020. During the years ended December 31st, 2021 and 2020, the company recognized revenue of $1.2 million and $10.2 million, respectively. all of which was a result of payments received under our license and collaboration agreement with Appleomics for the development and commercialization of UPIL S-LAN and GMI 1687 in Greater China. The company's research and development expenses increased at $12.9 million for the quarter ended December 31st, 2021, as compared to $11.7 million for the fourth quarter of 2020 due to higher development expenses related to manufacturing costs for UPIL S-LAN and increased costs for I&D-enabled activities of GMI 1687 Research and development expenses for the year end of December 31st, 2021 increased to $47.5 million as compared to $44.9 million in the prior year. The increase in expense was due to higher clinical development expenses related to our ongoing global phase three clinical trial of uproxilin in individuals with relapsed refractory AML, increased manufacturing costs, and increased IND enabling activities related to GMI 1687. The company's general administrative expenses increased to $4.5 million for the quarter end of December 31st, 2021, as compared to $4 million for the fourth quarter of 2020. General and administrative expenses for the year ended December 31st, 2021, increased to $17.1 million as compared to $16.7 million in the prior year. These increases were due to higher recruiting, consulting, and legal expenses incurred in 2021, offset by lower personnel-related expenses. I'd now like to turn the call back to Harut.

Thank you, Brian. Before I conclude our remarks and begin the Q&A, I'd like to leave you with the following thoughts. The top-line data from our Euproleteran Registrational Trial in AML will undoubtedly be transformative for the organization. As the survival data matures, we are preparing for a successful regulatory submission and commercialization. Our belief is that drug combinations targeting both tumor-intrinsic and microenvironment extrinsic pathways of AML will be essential for the successful clinical translation of new, more effective drug combination strategies. We are leading this effort. Finally, I believe that there are significant value-creating opportunities here at GlycoMedix beyond your proletariat, and I look forward to stewarding your investment in our company to realize this value for the benefit of patients and shareholders who are counting on us to deliver. I'd now like to open the lines for Q&A. Operator?

Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, please press the pound key. Stand by as we compile the Q&A roster. Our first question comes from Zigda Jalla of Roth Capital Partners. Your line is open.

Good morning. Thanks for the really helpful update. I just have a few questions. I think the first one is just starting off with 2093, that program, we're collecting three. We're just kind of curious around the strategy for wanting to perhaps partner at before the program even gets into the clinic. And just was wondering how you were thinking about it versus perhaps partnering 1687, since it seems like your pipeline is more oncology-focused versus sickle cell.

Sure. Good morning. Thank you, Zachary, for that question. So I'll say a couple of things and then turn it to our chief business officer, Armand Girard, who is with us. So obviously, as we move your proletariat forward, we're very focused on it. At the same time, we're getting our additional therapies to key milestones that can open up doors for potential partnerships. And the Galactan-3 program is really on that. So with the 2093, we're very excited about that given its role beyond oncology. So Armand, maybe some color on how we're thinking about that and 1687. Yeah.

Hi, Zey. Good morning. So the first thing to highlight about 2093 is we wanted to get to, I guess, three critical success factors for the nominating a development lead. The first is we wanted to have a compound that was very potent for the target but exquisitely selective, and we've achieved that with 2093. But importantly, we also wanted to get to an oral colectin-3 inhibitor. If you look at galactin-3, you'll find that the wealth of data is in the fibrosis setting. If you look at cardiac fibrosis, there's actually an approved diagnostic looking at serum galactin-3 levels, and based on that, cardiologists should intervene aggressively in those patients because they're at high risk of mortality or hospitalization. But I could create the exact same story in diseases like NASH, IPF, where the levels of galactin-3 are overexpressed. And so our thinking is that now that we have a development lead identified, it's the perfect time to get this compound into partnerships' hands who have a greater experience and depth of understanding in the fibrotic setting. And so that's exactly what we're trying to do is we've got a great lead. We think it's a best-in-class lead. But fibrosis is not our expertise, and so we need to get that in other people's hands and maximize the value of the compound.

And 1687? Seems very helpful.

Yeah, with 1687Z, just to touch on that, I mean, I think we're getting to that point. As you know, our focus is on the IND submission. We're going to have a pre-IND meeting. once we get that guidance from the FDA, that's going to be the go from a potential partnership perspective. So we want to get the tox package. It's going to be clean, but we want to get all the IND put together, and that will be the start of, let's say, discussions.

Thank you. And then can you provide an additional color on how you're thinking about accelerating the development strategy for 1687? or, you know, what the study could look like. I know it's still being determined, but just any additional color, because a lot of folks were very interested in the previous sickle cell programs. I imagine folks are really curious here as well.

Yeah, and we're very excited about that as well, Zee. I mean, as you know, 1687 benefits from the tremendous data that we have with Trivipenzel. From that trial, we know, as you know, that it's critical to do fast intervention. That's why we were very focused on ensuring that 1687 is subcutaneously bioavailable. And there's very strong work having now on advancing the IND submission. To your point, how does that trial look like? It's a bit too early to tell, but maybe a bit more color from our model of how we're thinking beyond the beyond the, you know, the IND submission.

Yeah. So, again, Z, I think that the thing you need to understand about these sickle cell patients that are having a crisis is they typically see a prodrome where they know that a crisis is coming on, and then that vaso-occlusive crisis builds and becomes, you know, excruciatingly painful over that kind of 18 to 24-hour period. So the point being is there's plenty of time to intervene in these patients, and the key to us is to get to those patients as soon as we can in the initial development of 1687. So that's going to be the conversation that we're going to be having with the FDA, is how do we move from, let's say, a phase one in healthy volunteers to, let's say, sickle cell patients, either in chronic state initially, but we ultimately want to get to patients that are experiencing VOC right off the bat. And so that's going to be the dynamic that we're going to be discussing with the agency.

And then thinking about catalysts here, is it possible that we might see even some initial safety data from patients from 1687 sometime this year?

Yeah, I wouldn't say that, but maybe, Armand, would you like to add something else?

Yeah, so, Zee, we don't have any concerns with regards to the safety side of the equation on, I'll call it, selectin inhibition. As you know, we've had a panselectin antagonist with rivopansil that was most potent on E. We have uprolessalin, which we're now dosing, you know, 10 to 12 days. never seen anything from a maximum tolerated dose, toxic dose in animals, never had an NTD or DLT in humans. So we suspect this is exactly going to be the case with 1687, which is an E-selectin-only antagonist. So to us, this is all about getting the efficacy and the dosing determined and getting that data I don't want to say we're cavalier about the safety side of things, but we think from a safety perspective, this program's de-risked.

Thank you. And then the last one here is just about the UPRO data in the new diagnosed patients. I know it's event-driven in terms of the timing of the readout, but I was just wondering if we should even think about, you know, again, you know, seeing some data during 2022 from that study. And then any additional details on whether you plan to use that phase two data in the package or after the NCI hands it over, do you then run the phase three portion of the study before submitting that for approval? And then lastly, any additional comments on what you plan to discuss with the FDA through your interactions plan for 2022, be it the CMC plans and things like that, anything that you think will be, you know, helpful.

Yeah, regarding the newly diagnosed AML patients, that is the NCI-sponsored trial, I mean, we are in a good situation in AML where we have really two shots at goal, our own company-sponsored trial in the relapsed refractory setting and also the NCI-sponsored trial in the in the novel setting. The NCI has not commented about the timing of the event, but as you know, it is an event driven by EFS, not OS. Typically EFS can be read faster than OS. So to your question, is it possible? Yes, it is possible for that data to be maturing, the phase two aspect of that to be maturing in 2022. And the way the registrational version works is that we actually are able to, if that data is positive, it's transferred to us and we have the opportunity to actually use that data in our registrational submissions. So once the time comes and we see the results, it can be either that we continue the phase three or if it's very positive, we stop the trial and then we will consider that from a registrational perspective or if the study is negative, then that trial will be stopped. So we have the opportunity to actually make that call later on if it's one file or if it's separate files, which is a good position to be in. And then you had another question, your last one, if you don't mind repeating.

So just about plans for your regulatory interactions with the FDA based on your BTD, you know, what you plan to discuss, what kind of things you plan to get cleared ahead of the NDA submission.

Yeah, no, I mean, that's actually a great point regarding, you know, having the ability to have multiple interactions with the FDA. We've had multiple interactions with the FDA in 2021, and we're planning more. Armand, do you want to comment maybe about that?

Yes, so Z, I mean, that's the beauty of BTD. So we've had multiple interactions from the CMC, but also from a non-clinical perspective. Haru touched on it in the script. You know, we've had multiple CMC meetings specifically. We've manufactured the registration batches to support the NDA. These batches are already on ICH stability. we've also submitted the data from those batches to the FDA under the IND. So with those batches complete, we're now shifting our gears towards the commercialization batches to support the market. So bottom line, what we're signaling is we're clearing the deck from a CMC non-clinical perspective so that the only remaining element is the clinical piece. And from a CMC perspective, We think we're ready for the NDA and now planning for commercial launch.

Perfect. Thanks, guys. Really appreciate it.

Thank you, Zagre.

Thank you. Our next question comes from the line of Ed White of HC Wainwright. Your line is open.

Good morning. Thanks for taking my questions. I think most of mine were already asked. So maybe I could just ask a question on the timing of the phase three. I know you've been saying post 2022. Does that imply 2023 we could see data or should we be thinking that data won't even be seen until out to 2024? And then do you, can you make any commentary on patient deaths perhaps due to COVID And do you anticipate having to break out those patient deaths separately to look at the patients in different cohorts?

Yeah, so good morning, Ed. Thanks for your question. So maybe just to tackle the second one first. We have seen a handful of patients die due to COVID. We don't anticipate that that's going to move the needle in our trial. So that's really kind of where we are. We extend the course. We continue the course. Regarding your first question on the timing of the 301 top-line readout, yes, you're right. We've said after year-end 2022. And maybe just to give you some color why we did that is these event-driven trials are are really a bit difficult to kind of anticipate so early on, given that it is an overall survival endpoint, and there are multiple factors that can attribute in that. As you know, one of the key things about our trial is that we have not censored transplant patients. That was a very active choice in the conversation with the agency, because we do believe that getting more patients to transplant is really the ultimate goal in this patient population. Obviously, the downside of that is from a timing perspective is, you know, patients who do make it to transplant generally live longer. So that means the data maturity takes a bit more. So we wanted to make sure that we signal some of that education to the marketplace that this is not a 2022 event. As many times I've heard and many of us have heard where you say, okay, full enrollment end of year, you add the average overall survival of these patients are, let's say, six months, seven months, so it should be ready in 2022. So that was really the key driver of why we signaled it's after year-end 2022. Now, to your second part of the question is, you know, out of 2022, but is it 2023, is it 2024? At this point, what we're saying is that we're going to be very carefully monitoring the full cohort, and as we get timing over the next few months, we should be in a better situation to address the timing, at least if not in a quarter way, at least in a half year way. So it will be sometime after 2022, I would say at this point, Ed, but stay tuned, more work on this.

Okay, thanks. And perhaps just a last question for Brian, just wanted to get your thoughts on cash burn. moving for 2022. Thanks.

So, Ed, yes, with ending, we'll begin 22 cash with $90 million in the bank. You know, we've been very consistent around $60 to $65 million spent over the last several years. I would anticipate 22 burn to be somewhere around that $60 million range, so that puts us in a good position going into 23 with, you know, cash well into second quarter of 23. Great. Thanks, Brian.

Thank you, Ed.

Thank you. And again, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, please press the pound key. Our next question comes from the line of Roger Song of Jefferies. Your line is open.

Great. Thank you for taking our question. Yeah, so most of the questions have been answered. Given your phase 3 or phase 2-3 useful AML study already started for some time, could you, Haru, maybe just remind us what is the powering assumption for those two potential pivotal studies? And also, what do you or your advisors think is the clinically meaningful improvement in those primary endpoint, like median overall survival in the EFS? Thank you.

Yeah, thank you, Roger. You know, great question. So, you know, just maybe to add some color on the NCI trial, as you know, the NCI Phase 2-3 trial is to evaluate euprolesterone in newly diagnosed patients 60 years and older with AML, just to, you know, for everybody's benefit. More specifically, with a randomized controlled trial design, they're looking at to see whether the addition of euprolesterone to standard seven plus three in older adult patients with previously untreated AML who are fit enough for intensive chemo will improve patient outcomes. So there are 268 patients that are now completed in the enrollment of the phase two, and that now triggers a planned interim analysis based on the events-free survival. So there are three potential outcomes really from the planned interim analysis of this trial. The trial could stop due to efficacy. The trial could proceed to phase three to gain more data on overall survival with the combination, or the trial could be stopped due to futility. So specifically, if the interim analysis achieves a hazard ratio of 0.64 or better, the data will be transferred to us Roger, to support the global regulatory filing in this particular population. Now, if the hazard ratio of 0.64 is not reached, the NCI will move forward to the Phase III portion. At that time, enrolling will resume to reach the sample size of 335 people. available patients per arm. So, total patients, it will be 670, inclusive of the Phase II patients, obviously. So, basically, this is to provide greater than 85% power to detect an improvement in median overall survival from 12 months to 16 months. So, you know, should the EFS analysis not show any benefit as defined by the hazard ratio greater than 0.83, then the trial could be stopped by the NCI for futility. We do not expect this to be the case as the trial has already passed the initial futility analysis earlier this year. So, you know, that's kind of where a bit of additional color as to what can potentially happen. I mean, the way we look at it is we're very focused on the relapsed refractory population. We think there is a significant unmet medical need in that population. And then if potential expansion into a newly diagnosed population, that would be an added plus for us to think about.

Got it. Yeah, that's very helpful. Thank you. All right, so in terms of the cash burn, I think, Brian, you said this $50 million this year. Just curious, did that burn include anything outside of those two pivotal studies for you, Pro, or anything else kind of included in terms of the clinical development? I know you're doing lots of the preclinical stuff, but just any clinical development plan included in the $60 million burn this year?

No, Roger, most of that spend is for remaining phase-free clinical trial costs, for manufacturing costs, for the rest of the IND-enabled activities for 1687, and then just the fixed overhead.

Got it. That's great. Thank you. That's all from me. Thank you, Roger.

Thank you. As there are no more questions in the queue, I'd like to turn the microphone back to Mr. Semerjian.

Thank you, and I would like to thank you for your time and attention. In the next several weeks, we will be at two conferences, at Cowan virtually and at Roth in person. I look forward to the one-on-one meetings that will be scheduled and to updating you on our progress and outlook. Thank you very much, everyone.

This concludes today's conference call. Thank you all for participating. You may now disconnect, and have a pleasant day.