CBIO - NASDAQ

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 opened for you. [Operator Instructions]. I would now like to turn the call over to Shari Annes, [Investor Relations 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 31, 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 Harout Semerjian, Chief Executive Officer; Brian Hahn, Chief Financial Officer; and Armand Girard, Chief Business Officer. We will start today's call with comments from Harout. 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 uproleselan, 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 Harout.

Thank you, Shari, and good morning, everyone. 2021 was a transformative year for GlycoMimetics. We advanced from a research-based company to a commercially focused organization. Our #1 priority was completing enrollment of our own Phase 3 pivotal trial evaluating uproleselan in relapsed/refractory AML patients. Towards the end of the year, recruitment for our trial increased significantly, reaching full enrollment in November. Within 2 weeks of enrollment completion of our trial, the Phase 2 portion of the NCI's Phase 2/3 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 negative impact -- 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 uproleselan. We are diligently collecting and preparing our Phase 3 data for analysis. Our Breakthrough Therapy designation provides us an opportunity to interact with the FDA on numerous occasions during 2021. Based on these interactions, we believe that our nonclinical 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 3 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, most importantly, whether the data could support a filing for accelerated regulatory approval, whether the Phase 3 portion will move forward, or whether the trial will stop. In the interim analysis, if the interim analysis is compelling, the NCI data in the newly diagnosed setting will be transferred to us for regulatory filing purposes. Externally, uproleselan is getting featured in clinical journals and expert forums. In September, the Phase 1/2 data supporting uproleselan'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 2 recent publications: one by the group at MD 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 2-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 uproleselan. 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 allogeneic 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 1/2 study are encouraging and expressed hope that this approach of targeting the bone-marrow niche will improve clinical outcomes in the Phase 3 trial. We are also pleased to see the role of E-selectin antagonism being discussed in the clinical educational forums. Last month, during the DAVA Oncology Acute Leukemia Forum, this novel extrinsic approach to targeting E-selectin mediated chemo resistance with uproleselan was highlighted during several expert presentations. During the plenary session focused on leukemia microenvironment, presentations from 3 medical experts review data implicating E-selectin as a key mediator of leukemic cell drug resistance and the potential role of uproleselan in deepening remissions. Collectively, this external recognition gives us great confidence of uproleselan's potential to positively impact the lives of AML patients. GlycoMimetics is chartering a new approach for treating leukemia. As you recall, leukemia lives in the bone marrow. There, leukemic cells induced the expression of E-selectin 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. Uproleselan represents this new approach of disrupting extrinsic factors of chemo resistance. We believe uproleselan 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 7 months on the job, I continue to be enthusiastic about uproleselan, about the pipeline and definitely about our people. To complement our strong team, we've added 3 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 uproleselan, accelerate competitive readiness, deeper medical expert engagement and broaden scientific education. Finally, Dr. Deepak Tiwari just joined us as Vice President, 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 uproleselan forward towards the potential submission of 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 5 additional operational highlights from 2021. First, our collaboration with Apollomics in Greater China made significant progress during the year. In January, the team secured Breakthrough Therapy designation in China for uproleselan and advanced from a Phase 1 bridging study to a Phase 3 registrational trial in relapsed/refractory AML. Second, we announced 3 investigator-sponsored trials collaborating with investigators at MD Anderson, at UC Davis and Wash U at St. Louis. All 3 ISPs 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 uproleselan 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 3 RESET and open-label extension studies with rivipansel 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 have highlighted the potential for GMI-1359 in breaking resistance in AML, particularly in patients with FLT3 mutations. We are exploring strategic options for this program. And fifth, we are advancing our galectin-3 program. We have nominated GMI-2093 and 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, Harout. As of December 31, 2021, GlycoMimetics had cash and cash equivalents of $90.3 million as compared to $137 million as of December 31, 2020. During the years ended December 31, 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 Apollomics to the development and commercialization of uproleselan and GMI-1687 in Greater China. The company's research and development expenses increased to $12.9 million for the quarter ended December 31, 2021, as compared to $11.7 million for the fourth quarter of 2020 due to higher development expenses related to the manufacturing costs for uproleselan and increased cost for IND-enabling activities of GMI-1687. Research and development expenses for the year ended December 31, 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 3 clinical trial of uproleselan in individuals with relapsed/refractory AML, increased manufacturing costs and increased IND-enabling activities related to GMI-1687. The company's general and administrative expenses increased to $4.5 million for the quarter ended December 31, 2021, as compared to $4 million for the fourth quarter of 2020. General and administrative expenses for the year ended December 31, 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 Harout.

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 uproleselan 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 GlycoMimetics beyond uproleselan, 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?

[Operator Instructions]. Our first question comes from

I just have a few questions. I think the first one is just starting off with 2093 programs with galectin-3. We're just kind of curious around the strategy for one thing to perhaps partner at before the program even gets into the clinic? And I 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?

Thank you,

Yes. So the first thing to highlight about 2093, is we wanted to get to, I guess, 3 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 galectin-3 inhibitor. If you look at galectin-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 galectin-3 levels. And if based on that cardiologist 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 galectin-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.

Yes, with 1687, just to touch on that. I mean, I think the -- we're getting to that point. We want to -- 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 goal 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.

And then can you provide any additional color on how you're thinking about accelerating the development strategy for 1687 or 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 program. So I imagine books are really curious here as well.

Yes. And we're very excited about that as well,

Yes. So

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

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

Yes. So

And then the last one here, 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, again, seeing some data during 2022 from that study. And then any additional details on whether you plan to use that Phase 2 data in the package or after the NCI hands it over, do you then run the Phase 3 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 planned for 2022, be it the DMC plans and things like that, anything that you think will be helpful.

Yes. Regarding the newly diagnosed AML patients, the NCI-sponsored trial, I mean we are in a good situation in AML, where we have really 2 shots at goal: Our own company-sponsored trial in the relapsed/refractory setting; and also the NCI-sponsored trial in the in the de novo setting. The NCI has not commented about the timing of the event. But as you know, it is an event driven by its EFS, not OS. Typically, EFS can be read faster than OS. So again, to your question, is it possible? Yes, it is possible for that data to be maturing -- the Phase 2 aspect of that to be maturing in 2022. And the way the registration of the 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 3. 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 on file or if it's separate files, which is a good position to be in. And then you had another question,

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

Yes. No, I mean we -- that's actually a great point regarding 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,

Our next question comes from the line of Ed White of H.C. Wainwright.

I think most of mine were already asked. So maybe I could just ask a question on the timing of the Phase 3, 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?

Yes. So maybe just to tackle the second one first. We have seen a handful of patients die due to COVID. So 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 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 and a 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 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, 6 months, 7 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, out of 2022, but is it 2023, is it 2024? Where 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 away, 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. And perhaps just a last question for Brian. Just wanted to get your thoughts on cash burn moving for 2022.

So I guess, with the ending -- we'll begin to cash with $90 million in the bank. We've been very consistent around $60 million to $65 million spend 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 cash flow in the second quarter of '23.

[Operator Instructions]. Our next question comes from the line of Roger Song of Jefferies.

So most of the question has been answered. Maybe given your Phase 3 or Phase 2/3 upro AML study already started for some time, could you, Harout, maybe just remind us what is the powering assumption for those 2 potential pivotal study? And also what do you or your advisors think is the clinically meaningful improvements in those primary endpoints, like a median overall survival in the EFS?

Yes. Thank you, Roger. Great question. So just maybe to add some color on the NCI trial, as you know, the NCI Phase 2/3 trial is to evaluate uproleselan in newly diagnosed patients 60 years and older with AML just to -- for everybody's benefit. More specifically with a randomized controlled trial design, they're looking at to see whether the additional uproleselan to standard 7+3 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 2, and that now triggers a planned interim analysis based on the event-free survival. So there are 3 potential outcomes really from the planned interim analysis of this trial. The trial could stop due to efficacy. The trial could proceed to Phase 3 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 achieved 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 is -- of 0.64 is not reached, the NCI will move forward to the Phase 3 portion. At that time, enrolling will resume and to reach the full -- the sample size of 335 evaluable patients per arm. So totally, it will -- total patients, it will be 670, inclusive of the Phase 2 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 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 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 a potential expansion into a newly diagnosed population, that would be an added plus for us to think about.

Got it. Yes, that's very helpful. Thank you. All right. So in terms of the cash burn, I think, Brian you said this $60 million this year. Just curious does that include anything outside of those 2 pivotal study for upro? Or anything else kind of included in terms of the clinical development? I know you're doing a lot 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 3 clinical trial costs, for manufacturing costs, for the rest of the IND-enabled activities for 1687 and then just the fixed overhead.

As there are no more questions in the queue, I would 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 2 conferences at Cowen, virtually; 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.