CBIO - NASDAQ

Good morning, and thank you for joining the GlycoMimetics Q2 2022 earnings call. At this time all participants are in listen only mode. Following management's remarks, we will hold a question-and-answer session. [Operator Instructions] I would now like to turn the call over to Christian Dinneen-Long company counsel at GlycoMimetics. Please go ahead.

Good morning. Today we will review our business updates and financial results for the quarter ended June 30 2022. The press release we issued this morning is available on the company's [email protected] 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 Bruce Johnson, Chief Commercial Officer. We will start today's call with comments from Harout, who will provide a broad overview of the business and the progress of our pipeline programs, followed by commentary from Bruce on the potential market opportunity for uproleselan. Brian will then provide detail on the company's financial position, and we'll open the call for Q&A. I would 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 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 pre-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 on the GlycoMimetics website. I'll now turn the call over to Harout.

Thank you, Christian. Good morning, everyone. Over the past quarter, we have continued to ramp up our regulatory and commercial readiness activity as we advanced the development of our lead program, uproleselan, currently in a Phase III registrational trial in relapsed refractory acute myeloid leukemia, or AML, and continue building a strong foundation for our potential evolution to a commercial-stage company. Experienced and dedicated leadership with a track record of successfully commercializing oncology and hematology assets is crucial to this evolution, which is why we are – we’re excited to have Bruce, our Chief Commercial Officer, on today’s call to share additional detail on these ongoing efforts. First, however, let me provide an overview of the business. As shared last quarter, one of our top priorities continues to be cleaning the data from the 70 sites and 388 patients participating in our Phase III clinical trial across the US, Europe, Canada, and Australia. The placebo-controlled trial is evaluating salvage chemotherapy with or without uproleselan. Recall that the primary endpoint of this trial is overall survival, and as we have previously disclosed, the Phase III trial was powered at 90% to detect the hazard ratio of 0.68 or better. Today, for the first time, I’d like to share an overview of the patient demographics from our Phase III trial. When designing our Phase III trial, our goal was to generally reflect our Phase I/II patient population and exclude patients that are not likely to benefit from the therapy. I’m pleased to say that Phase III population is broadly similar to that of completed Phase I/II study with respect to age, severity of AML, prior stem cell transplantation rates, and distribution of relapsed and refractory patients. The median age was 58 years old. 33.5% of the Phase III participants were refractory patients, with the other 66.5% falling into the relapsed category. Of the relapsed patients, 19% of the Phase III population had a prior duration of remission less than six months. In terms of prior therapeutic background of this Phase III population, 18% previously had hematopoietic stem cell transplantation, or HSCT, while 16% had undergone more than two induction regimes. PLN risk stratification was broadly consistent with Phase I/II population. For a more detailed breakdown, you can find the full patient demographics tables in our earnings press release. The bottom line is, the patient population enrolled in Phase II and in the Phase III programs with uproleselan in the relapsed refractory setting are broadly similar and reflect the patient population clinicians are seeing in their practice. As for the timing of the event trigger, we have previously disclosed our projection of midyear 2023 for this milestone, with disclosure of the topline data results shortly thereafter. We will continue to monitor events and provide appropriate updates to this projection as needed. As a reminder, we have already been granted FDA fast-track and breakthrough therapy designation for uproleselan in the relapsed refractory AML, allowing us to rapidly move to regulatory submissions. As we draw closer to this milestone next year, we remain confident that by disrupting the protective interaction within the bone marrow microenvironment, uproleselan has the potential to transform outcomes in AML patients by hopefully achieving deeper, more durable remissions, higher rates of measurable residual disease MRD negativity, bridging more patients to potentially curative stem cell transplants, and ultimately improving overall survival. In addition to our Phase III registration trial, uproleselan is also being evaluated by the National Cancer Institute, or NCI, in an independent, randomized, open-label trial in frontline newly diagnosed AML patients who are 60 years and older. This clinical study is evaluating whether the additional of uproleselan to a standard cytarabine, daunorubicin regime of 7+3 in older adults with improved patient outcomes. The Phase II portion of this Phase II/III trial completed nrolment of 267 patients last November, and as per protocol, the NCI has suspended further nrolment in anticipation of its planned interim analysis. When the outcome of the NCI’s event-free survival analysis of the Phase II trial is communicated to us, we plan to issue a press release. To be clear, the NCI trial gives us the opportunity to demonstrate benefits in a distinct patient population and potentially expand our label to include frontline AML. I’d also like to reiterate that in addition to advancing two registration-stage programs, we have several investigator-sponsored trials currently evaluating uproleselan’s potential in additional hematological indications. Studies are underway to demonstrate the benefit of adding uproleselan to venetoclax HMA combinations in patients ineligible for intensive chemotherapy, as well as in combination with salvage therapy for secondary or treatment-related AML. We continue to collaborate with the principal investigators of these trials with a mutual goal of publishing their findings at major medical meetings. These trials provide GlycoMimetics with the opportunity to expand the potential application of uproleselan into additional areas of unmet medical needs, and we are greatly appreciative of our investigator partners for their efforts to advance this goal. We believe the enthusiasm of clinicians to engage with uproleselan in this manner reflects both the high degree of unmet needs in this patient populations and the exciting potential that uproleselan has to address these gaps in the care continuum. Our pipeline of innovative glycobiology-based therapies extends beyond uproleselan, and I would now like to turn to recent updates on the progress we have made with our sickle cell disease program, GMI-1687. I am pleased to report that the FDA accepted our IND application to proceed with a Phase I clinical trial of GMI-1687 in healthy volunteers. While we are encouraged by this positive update, in line with our existing business strategy, we are focusing company resources on uproleselan development and potential commercialization. Consistent with our past communications, with this IND acceptance, we believe 1687 is well positioned for partnership to further advance this promising molecule. As a reminder, GMI-1687 is a highly potent E-selectin antagonist, initially being developed to treat acute vaso-occlusive crisis, or pain crisis, in sickle cell disease patients. E-selectin is believed to play a major role in the cascade of events leading to clots and blockages that cause patients’ pain crisis, which could ultimately lead to events like a stroke or permanent organ damage. Because GMI-1687 offers the potential for self-administration in an injectable, subcutaneous dosing form via a prefilled syringe or auto injector, it could be administered at the onset of the pain crisis to disrupt the underlying inflammatory cascades and restore normal blood flow, potentially blocking damage and pain created by occluding blood flow to the organs. Given that there are currently no FDA-approved therapies in the treatment of acute VOCs in sickle cell patients, we are optimistic about the promise of this program to address the high unmet need and long-term health consequences for this population. Despite recent advances in the treatment of sickle cell disease, the impact on reducing – on reduction of frequency and severity of the VOCs has been limited for the nearly 100,000 patients in the US. We look forward to continuing to provide updates as we review potential next steps for this program. As we continue to advance the Phase III uproleselan trial towards its overall survival events trigger, currently expected in mid-2023, and make progress across the rest of our pipeline, with the recent acceptance of our IND application for our next asset, GMI-1687, we have established strong momentum in our continued evolution to a commercially-focused organization. We are hard at work preparing for uproleselan’s anticipated market entry, and I’d like to hand the call to Bruce to provide detail on the team’s early commercial development work, the market opportunity, as well as an overview of the current AML landscape. Bruce?

Thanks, Harout, and thanks to everyone for joining our call today. I'd like to discuss uproleselan's potential market opportunity by providing some background on our early commercial development efforts, as well as further context on the AML landscape and the limitations of existing standard-of-care therapies. I'll close out with some insights into why we view uproleselan as a therapy that we hope will be uniquely positioned to disrupt a market in serious need of transformation and address the unmet needs of AML patients. The focus of our early commercial development efforts has been in four key areas: first, to drive awareness and educate medical experts on the role of E-selectin in AML and how this glycoprotein on the endothelial surface of the bone marrow vasculature creates a permissive microenvironment for leukemic cell survival and proliferation; second, to raise awareness of uproleselan's unique and differentiated mechanism of action as a first-in-class E-selectin antagonist poised to disrupt the standard of care in both relapsed refractory and newly diagnosed AML fit for intensive chemotherapy; third, to drive awareness of uproleselan's clinical development program in AML; and forth to develop a deep understanding of the market landscape in the U.S., E.U., U.K. and Canada, the commercial opportunity for uproleselan, and to evaluate early perceptions of a blinded product profile with AML experts, community hematological oncologists, or heme/oncs, and payers. To date, we've conducted extensive primary and secondary market research to understand the AML landscape and the limitations of existing standard-of-care therapies. This includes target product profile, or TPP, primary market research with both academic AML experts and community-based heme/oncs. All experts included were investigators in trials, published research in AML, and were involved in regional national guidelines. The objective of this research was to gain physician insight into newly diagnosed and relapsed refractory AML treatment landscape, current unmet medical needs, and how the future AML landscape will evolve. We also wanted to obtain reactions from AML experts and community heme/oncs to a potential TPP that might address the unmet medical needs, with a focus on efficacy benchmarks and expectations for clinical use. To provide some background, AML is one of the most common types of leukemia in adults, with a global median incidence rate of almost 2.3 cases per 100,000. In the U.S., there are estimated to be more than 55,000 people currently living with AML and more than 20,000 adults in the U.S. diagnosed annually. A study presented at the National Comprehensive Cancer Network, or NCCN, Annual Conference this past March indicated that the incidence of AML and deaths among AML patients are increasing worldwide. Despite recent advances, AML unfortunately remains an area with significant unmet need. Long-term patient outcomes are poor, with roughly 70% of newly diagnosed patients relapsing within three years, and a disappointing five-year overall survival rate of 29%. In terms of current standard-of-care therapies, AML is a chemo-sensitive disease, and the main treatment for this patient population is chemotherapy. However, chemotherapy is not targeted and often results in residual leukemic cells that may result in relapse. Beyond chemotherapy, many of the newer therapeutic options for AML are limited in their ability to achieve deep, durable, complete remissions, or have toxicity concerns. These therapeutic options are also often used for a select few patients who harbor specific biomarkers, limiting their utility in broader populations. Compounded by these factors, there is no standard of care treatment regimen for relapsed refractory AML patients eligible for intensive therapy. As one expert recently stated, we are not curing a lot of people with AML, certainly not without transplant. When treating AML, the goal is to put the leukemia into complete remission, with bone marrow and blood cell counts returning to normal. Recently measurable residual disease, or MRD, negative status has emerged as an important prognostic factor for longer survival and decreased risk of relapse post allogeneic stem cell transplant. Illustrating that point. the five-year overall survival rate for patients who are MRD negative is 68%, versus 34% for those who are MRD positive. Similarly, the three-year relapse estimate is 22% for MRD negative patients versus 67% For MRD positive patients. Current NCCN recommended regimens achieve complete remission with complete hematologic recovery in 20% to 30% of relapsed refractory patients, MRD negativity in only 15% to 25% of patients, and allogeneic stem cell transplant rates of only 20% to 30% of patients in first relapse. The median overall survival period is approximately six months in the population evaluated in these studies. Feedback from AML experts indicates that large, well-controlled, randomized clinical trial, establishing novel agents in this setting will help redefine a new standard of care. As part of our efforts to understand the AML market, we continue to see strong positive response to a blinded product profile for both relapsed refractory and newly diagnosed setting. In blinded TPP primary market research with AML experts, community heme/oncs, and payers in the U.S., E.U., U.K., and Canada, all physicians interviewed expressed a high level of interest in the E-selectin mechanism. In relapsed refractory setting, physicians would add a product matching the blinded TPP to intensive chemotherapy if it exceeded their CR rate and OS threshold for use in clinical practice. In first line, median OS, or median overall survival, is the most important endpoint. Physicians found the overall survival benefit as the inflection point for use in their clinical practice. All respondents rated the blinded TPP favorably and felt that it would be a significant advance to have a new drug with a non-overlapping mechanism of action that, when added to standard therapy, could aid in achieving deeper, more durable remissions, higher rates of MRD negativity, and improved overall survival, without added toxicity. As new therapeutic options emerge, the prevalence of relapsed refractory AML will likely increase over time. And on average, patients will receive greater than two to three [Audio Gap] therapy over the course of treatment. As a result of this trend, novel agents that can enhance the effects of currently available therapies and bridge more patients to potentially curative options, or patients to potentially curative options such as allogeneic stem cell transplant, could be a major treatment advanced. Therein lies what we believe is a significant opportunity for uproleselan to potentially transform outcomes in AML, if we achieve our target product profile. In combination with salvage chemotherapy, we believe that uproleselan has the potential to be the first regimen in over 25 years to demonstrate broad clinical benefit in relapsed refractory AML, regardless of cytogenetics or mutational status. Based on available publications, we estimate in the top seven markets, there are over 25,000 relapsed refractory AML patients, of which about 40% are eligible for intensive therapy, such as a potential regimen of uproleselan plus salvage chemotherapy. If we are successful in our current Phase III trial and achieve our TPP, we envision pursuing development uproleselan for AML patients who are not eligible for intensive chemotherapy, which, according to our estimate, could more than double the market opportunity. And depending upon the results of the MCI study, we may also explore the significantly larger frontline AML market opportunity. So, in summary, assuming we achieve a label consistent with our TPP, establishing uproleselan in combination with intensive chemotherapy in both relapsed refractory and newly diagnosed AML is the first phase of our multi-phase lifecycle management plan for our E-selectin antagonists portfolio. Physician awareness, enthusiasm, and willingness to prescribe a novel therapy that is consistent with our target product profile is already present. The market opportunity is significant. And having spent the past 20-plus years focused on launching products in the AML arena, I'm quite excited by this opportunity and look forward to further exploring the potential to expand into additional indications down the line, broadening our reach into additional patient populations in need of innovative treatment options. Brian, I'll now turn it over to you to provide an overview of our financial results.

Thank you Bruce. As of June 30 2022. GlycoMimetics had cash equivalents of $60.2 million, as compared to $90.3 million as of December 31 2021. We continue to expect our current cash resources will fund our operations into the third quarter of 2023. The company's research and development expenses decreased to $8 million for the quarter ended June 30 2022, as compared to $10.2 million for the same period in 2021. The decreased expenses were primarily due to lower clinical trial costs related to our ongoing global Phase III clinical trial of uproleselan in individuals with relapsed refractory AML. With the completion of patient enrollment in November 2021, clinical sites are being closed as data collection and cleaning occur. As the Phase III data matures, we will continue to closely manage our R&D costs to ensure that we are appropriately allocating resources for potential commercialization of uproleselan. The company's general and administrative expenses increased to $5.5 million for the quarter ended June 30 2022, as compared to $4.2 million for the second quarter of 2021, primarily due to commercialization startup expenses for uproleselan and other administrative expenses resulting from the easing of COVID restrictions. I'd now like to turn the call back to Harout.

Thank you, Brian. As I approach the one-year anniversary of my appointment as CEO, I am more excited than ever about our company's transformative work, particularly as we gear up towards a significant inflection point expected in 2023. We look forward to providing further updates on our clinical pipeline as we pursue our mission and continue our evolution into a clinical -- into a commercial-stage company capable of delivering these therapies to the patients who need them most, and we deeply appreciate your continued support. I'd now like to open the lines for Q&A. Operator?

Our first question comes from the line of Boris Peaker of Cowen and Company.

First, I just wanted to ask, on upro Phase III trial, the enrollment obviously completed in November of last year. I'm just curious if you could comment on how the OS events are tracking versus projections.

Yes, and just as a reminder for everyone, we have completed our enrollment in our Phase III in November 2021, and we are projecting an overall survival events maturing in midyear 2023. So, Boris, that's kind of -- you know, it's still tracking in line with our previous projections. But at the same time, this is all projections, so we're continuously monitoring it and making sure that if there are differences, that we communicate them appropriately with time. So, at this point, we're still tracking towards that mid-2023.

Got it. And my next question here is on, you mentioned there are a number of uproleselan studies testing in a combo with venetoclax. I'm curious, when will we see some initial results from that combination?

Excellent question as well. So, well, one of the –one of the several ISTs that are going on is the combination with venetoclax and HMA. Obviously, the principal investigators are responsible for their own data and when do they present it, so that we don’t have a clearer guidance from them when they plan to do that. Having said that, Boris, I wouldn’t be surprised if we start seeing some of this data start coming in, I would say even as early as this coming ASH, given that these are – some of them are open label trials. So, you know, we stay tuned, but I wouldn’t be surprised if I start seeing it then.

Our next question comes from Roger Song of Jefferies.

Maybe, Harout, it's very helpful you provided these baseline characteristics for the Phase III. Can you just -- I understand in broad strokes, the characteristic seems broadly similar between 301 and 201. But when we look at the granularity, we do see some difference in terms of like duration of the prior remission in the prior greater than 2 induction, and also the ELN risk category more favorable and less adverse. So, would you characterize this 301 less kind of severe in terms of patient baseline compared to 201, slightly? Also, how would you compare 301 study versus historical study using chemotherapy or 7+3?

Yes, excellent questions, Roger. Yes, I mean, when we take a look at our patient characteristics, Roger, what we're characterizing it is we're saying it's broadly similar with our Phase II. And it's not exactly similar, to your point; it's broadly similar. I would say a couple of things about that. Keeping in mind that age, for example, as I said, it's quite similar. The distribution of relapse and refractory are quite similar. The vast majority of the patients in both trials have an adverse risk category. One is 40%, one is 50%, so 50% was in the Phase II, 40% is in the Phase III. Keep in mind, Roger, that the Phase II was a handful of sites in the U.S. with 66 patients, while the Phase III is 388 patients, 70 sites across the world. So, a few percentage points, a couple of patients here and there can make a big difference in the percentage number on the Phase II. So, that would be one comment. And then the second comment I would say is, let's not forget that all these are relapsed and refractory patients, AML patients, whose prognoses are in months, unfortunately. So, that's kind of why, when you put all these things together, we believe they're broadly similar to each other, and they're broadly similar as well with other trials in the marketplace. We've done a deep dive on that as to what are different trials in the marketplace, and what we're coming up with is a broadly similar patient population in the controlled trials. There are a handful of trials out there as well that we were aware of that are retrospective in nature or are single-site in nature that might report a bit of different outcomes. But that's kind of where it's important to look at, let's say, age groups. Obviously, you would know a 58-year-old patient can be quite different than a 50-year-old patient, and so on and so forth. So, we think -- that's kind of a longwinded answer to your question of they're broadly similar to the Phase II and also to historical market practices.

Got it. Yes, that's very helpful. And in terms of the NCI study, understanding they're controlling this data and clean up the data right now, how often you will get updates from NCI? Would they give you like a real-time update and to the point they will say, okay, this is the final data and you can issue the release?

Yes, so our working methodology with NCI is that once they complete their analysis, then they would give us the go-ahead with that. So, without them completing the analysis, we wouldn't get any updates from them, Roger. And that's something that they have not communicated to us when will they do that. Looking at it from the outside in, obviously, as a reminder for everyone on the call, the primary endpoint of the Phase II portion of this Phase II/III adaptive trial is EFS. And generally speaking, EFS reads out faster than OS. They have enrolled 267 patients, more or less. The press release for the full enrollment of the Phase II NCI trial was within 2 weeks of our own trial, so both trials enrolled at the same time. One is in EFS, one is an OS. We're saying the OS is mid-'23. So, from our perspective, we think it will be before that, obviously, but they haven't officially communicated. What we are committing is, once we have that, we will issue a press release.

Excellent.

Does that answer your question, Roger?

No, that's very good. Maybe just last one from us is, in terms of the BD activity, now you get the 1687 with the R&D, and also you have a couple of other assets in the pipeline you're seeking partnership. Just any comments around the BD progression? And then, noticing the cash runway is into your potential Phase III data readout, would this be the kind of ahead of this cash runway and then you can extend further?

So, BD obviously remains a clear focus. So, maybe a couple of things about 1687. I mean, we’re very excited about this program. Sickle cell disease remains one of the diseases where there’s high unmet medical need. There have been many attempts, different therapeutics coming into the market. Unfortunately, what we’re seeing is on the patient level, the 100,000 patients in the U.S. continue – the vast majority of them continue to have vaso-occlusive crisis. They know the pain is coming, and in a way, they have minimal options to do something about it. So, coming up with a new therapeutic option where patients do not have to end up in the emergency room, they are able to take this subcutaneously bioavailable auto-injector or something of that sort, is really something very motivating for us. Partnership – it was very important for us, Roger, to have the IND under our belt, because as you can imagine, that changes quite a bit the partnership discussions when we have that FDA okay to proceed into patients. So, we’re working hard on that, but I want to reiterate that we’re only going to seek quality partners who are not just aligned from a financial perspective, but also with their commitment to this patient community perspective, Roger. So, that’s going to be very important. And to the second part of your question, given the cash runway, the market has put all of us into a much more clear way of how should we prioritize our activities and our company cash, and we’re really doubling down on uproleselan at this point. We see that light at the end of the tunnel. We see the Phase III data maturing, and we want to make sure that we are well prepared and well positioned, should that data be positive, that we’re able to activate everything possible to get it to patients as fast as possible. So, that’s why we’re preserving our cash to focus on that, while seeking additional opportunities for be it 1687 or be it 1359. 1687 is the third asset we're going to get into the clinic, hopefully so’n, with a partner. Whenever that comes, we will communicate it.

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

This is Steve on for Ed White. First question, on the recent workforce reduction, has that been completed, and should we expect to see any quarter-over-quarter expense reductions during the year?

Yes, I'll take the first part of your question, and maybe Brian Hahn, our CFO, can weigh on the second part. So, we have reduced our workforce, particularly in the early research team. That's kind of where, now that we have multiple assets coming from our pipeline, we think we have enough at this point to really focus on pulling forward our Phase III and beyond, so that was the intent of it. It wasn't meant for a significant reduction in cost, but rather a reprioritization of investment from the early bench science part of the organization more into the late medical affairs, commercialization, regulatory affairs part of our organization, which is really important. But what would the impact be from a financial perspective? Brian, do you want to comment on that?

Thanks, Steve. We’ve been, as noted, we’ve been burning about $15 million a quarter. And again, with some of these reductions, not a material impact on cash burn, so I would anticipate maybe a slight decrease, but not much.

As there are no more questions in the queue, I would like to turn the microphone back to Mr. Semerjian.

Thank you very much, operator. I would like to thank you for your time and attention. As a reminder, in September, we are planning to be in person at the H.C. Wainwright Global Investment Conference in New York. I look forward to the one-on-one meetings that will be scheduled and to keeping you updated on our progress and outlook. Once again, thank you very much, everyone, for joining our call.