GlycoMimetics, Inc.

Good morning, and thank you all for joining Glycomimetics Call. At this time, all participants are listen-only mode. Following management 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 zero on your touch-tone telephone. I would now like to turn the call over to Sherry Ines of Investor Relations Group at Glycomimetics. Please go ahead.

Good morning. Today we will review our accomplishments and financial results for the period ended June 30, 2021. We'll also update you on recent achievements. The press release we issued this morning is available on the company's website at www.glycomamedics.com under the Investors tab. This call is being recorded. A dial-in phone reply 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 Rachel King, Chief Executive Officer, Dr. Eric Feldman, Chief Medical Officer, and Brian Hahn, Chief Financial Officer. Our new CEO, Harut Samarjan, is also on the call with us this morning. We'll start today's call with comments from Rachel and Eric, Brian will follow Rachel to provide an overview of the company's financial position, and Harut will add some initial comments. We'll then open the call to Q&A. I'd like to remind you that today's call will include forward-looking statements based on current expectations. Forward-looking statements contained on this call include, but are not limited to, statements about the company's product candidates, you professor, Lance, GMI 1359, and GMI 1687, and our other pipeline programs, along with our operations and cash position. 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 Glycomimedics filings with the SEC, which are available from the SEC or on the Glycomimedics website. I'll now turn the call over to Rachel.

Thank you, Sherry. As we've said in prior calls, our primary operational focus is on advancing three uprolestolant administration programs in AML. Our company-sponsored Phase III trial in relapse refractory AML, the National Cancer Institute's trial in newly diagnosed patients, and the registration study in China being conducted by our partner, Apalomax. I'm pleased to report today that recruitment rates in both our own Phase III and the National Cancer Institute's Phase II portion of its Phase II-III trial continue to support an expectation that enrollment will be completed by the end of this year. During the quarter, and just after it's closed, we announced the initiation of three new investigator-sponsored trials, or ISTs, that expand the breadth of our UPRLS land clinical research activities. There are now six trials evaluating upralesolan, including three registration trials and three ISTs. The support of clinicians who are enrolling patients in our global studies and now the new ISTs has made it possible to broaden the scope of our upralesolan clinical research to address unmet needs of patients with hematologic malignancies. Leading clinicians, academic centers, collaborative networks, and regulatory agencies are working with us as upralesolan continues to garner significant attention and interest The breakthrough therapy designations granted by both the FDA and the Chinese Health Authority, we believe, have added momentum for this program worldwide. To reiterate, we're confirming that we anticipate completion of enrollment of all 380 patients in our company-sponsored registration trial by the end of this year. As you know, the readout on the primary endpoint is event-driven. As we approach completion of enrollment and as we acquire additional data on events to date, we plan to give guidance as to timing of top-line data. In parallel, the NCI-sponsored Phase II Registration Trial that's enrolling uprolessment in newly diagnosed older adults with AML also continues to accrue participants at a steady pace. Based on the public information provided by NCI to date, we continue to anticipate that the trial will complete enrollment of the Phase II portion by year end, supporting a subsequent interim analysis of event-free survival, or EFS, in the trial's initial 262 patients. To be clear, if the NCI Alliance's interim analysis is positive, the data will be transferred to glycomimetics to support our regulatory filings. Together, the glycomimetics and NCI-sponsored programs will constitute a large data set of over 500 AML patients. We would anticipate filing for approval for treatment of patients in both settings should both trials hit their primary endpoints. Epilomics last quarter announced that it had dosed the first patient in Greater China, in a Phase I clinical trial for treatment of adults with relapse or refractory AML. This study is a bridging study that's expected to allow Apilomix to expeditiously advance development to a Phase III registration trial in Greater China. Beyond working with the NCI and Apilomix, we've now announced three new trials in which uprolesline is being paired with a variety of chemotherapy regimens and other AML and multiple myeloma therapies. These investigator-sponsored trials complement our registration trials and should begin to produce data in 2022. They provide us three additional perspectives and could well provide a basis for expanding use of UPRO-Less land across the AML spectrum and potentially beyond AML as well. I'd like to add that all three of the institutions sponsoring these trials have collaborated with us in the past and reflect the growing enthusiasm for UPRO that I mentioned before. I'd now like to turn to Dr. Eric Feldman, our Chief Medical Officer, to describe each of these in a bit more detail. Eric?

Thank you, Rachel. I'd like to begin by providing context for the three investigator-sponsored trials. We're often asked why ISPs are important. First and foremost, these trials provide glycolymetics with an opportunity to extend the potential use of uprolithon in key areas of unmet need. Investigators see in real time both how newly approved therapeutics are working and how even advances often leave continued opportunities for improving patient outcomes. Our Phase III and relapsed refractory AML and the NCI's trial in newly diagnosed AML address those patients undergoing intensive chemotherapies. As you know, with increasing frequency, older patients with AML and those with significant comorbidities are alternatively treated with less intensive therapeutic regimens such as the combination of venetoclax and a hypomethylating agent. Despite the progress seen with the venetoclax HMA regimen and other molecularly targeted agents, investigators are seeing limitations in terms of the depth and durability of responses. In particular, patients with adverse risk features, including patients with secondary AML, and in those with specific poor risk biological profiles, are not achieving high MRD negative responses, leading to early relapses. This is where uprolizolone may have an important role and is the focus of our two ISTs in additional high unmet need frontline AML populations. The first IST in AML is being conducted at the University of California, Davis and was announced in July. This trial is especially exciting in that we anticipate that it will shed light on what we believe is an important opportunity to further improve outcomes by combining our drug with the venetoclax HMA regimen. Although uptake of venetoclax HMA in the frontline unfit AML setting has been strong, and while 60 to 70% of patients achieve a response, the responses are incomplete in approximately half the patients. As discussed earlier, only a minority of patients achieve an MRD negative response, reducing durability and leading to relapse. A strong scientific rationale for adding upro was demonstrated in preclinical studies done at the MD Anderson Cancer Center and reported at last year's ASH meeting. This research showed that the addition of uprolessalon completely restored sensitivity in a xenograft model using cells from a patient that was resistant to vinagrax and a hypomethylene agent. Additional preclinical data has also demonstrated that prior exposure to HMAs increases the expression of E-selectin ligand on the surface of blast cells, making them more resistant to chemotherapy and more likely to benefit from treatment with the addition of rupalessalon. The UC Davis IST will be the first clinical trial to potentially generate human data supporting our preclinical findings. Importantly, given the safety profile we have seen so far in our Phase I-II data, we believe that uproleslon may be one of the few drugs that in a chemo combination actually improves outcomes without adding incremental toxicity. Among the study endpoints will be the critical evaluation of the improvement in patients achieving a full CR and an MRD negative CR compared to rates reported with azacitidine plus venetoclax alone in the Viali A registration trial. In late July, we also announced a second IST in AML, a Phase 1b-2 study evaluating upraleson added to cladribine plus low-dose cytarabine in patients with treated secondary AML. The principal investigator is Tapan Khadia, an associate professor of leukemia at the University of Texas MD Anderson Cancer Center. Patients with treated secondary AML meaning those who received HMAs as part of treatment for a prior myelodysplastic syndrome, have an extremely poor prognosis with current therapies. This is a growing population of patients as the use of HMAs continues to increase in MDS. As noted previously, our preclinical and clinical research supports the potential for patients previously exposed to HMAs to benefit from the addition of buprolessalon to current treatment regimens. If the new study demonstrates that targeting E-Selectin with Euproleslin could help to overcome resistance to other therapies, this would be a significant achievement that underscores the broad potential of our drug candidate. Specifically, this trial is designed to demonstrate the safety and tolerability of the combination therapy, as well as to evaluate whether Eupro can increase the rate of response in this highly resistant group of patients. The last IST I will discuss, which we announced in April, is being conducted at Washington University in St. Louis. Dr. Keith Stocker O. Goldstein, professor of medicine at the Wash U School of Medicine, is the principal investigator. This is a randomized phase two study evaluating uprolizumab as a prophylactic agent to reduce GI toxicities associated with high-dose melphalan in autologous hematopoietic stem cell transplantation for multiple myeloma. GI side effects are the dose-limiting toxicities of high-dose melphalan in auto-transplant, and our preclinical data have demonstrated a protective effect of rupalesolone against mucosal damage. In addition, our Phase II trial demonstrated the potential of our drug to mitigate severe mucositis in relapsed and refractory AML patients undergoing intensive chemotherapy. Hence, we are optimistic about what we may learn. The WashU clinicians will be the first to look closely at the potential of upralesolam to attenuate GI toxicities in multiple myeloma patients undergoing transplant.

If this placebo-controlled study demonstrates... It seems we've lost Dr. Feldman, so I'll pick up the call. As we think about the opportunities before us with our three ongoing registration trials and these exciting ISTs, we believe the enthusiasm of clinicians for upralesolam reflects their shared vision for UPRO's potential as a foundational treatment in AML, as well as its potential in other hematologic malignancies. The broad clinical program of company-sponsored, NCI-sponsored, now investigator-sponsored trials supports our vision, namely to establish UPRO as a foundational therapy across the entire spectrum of AML. Simply put, UPRO-Lessland targets the bone marrow microenvironment by inhibiting pathways that protect cancer cells from the effects of chemotherapy. This is a novel approach that we believe could be broadly applicable across the spectrum and range of therapies used for relapse refractory or newly diagnosed patients. Before completing the summary of our clinical work, I'd like to remind you that during the second quarter at the meeting of the American Association for Cancer Research, or AACR, we presented a poster on our ongoing Phase 1B study of GMI1359, a dual antagonist of E-selectin and CXCR4. This study was designed as a proof-of-concept study evaluating biomarkers of cell mobilization. Our Duke University collaborators reported on biological activity as demonstrated by cell mobilization, redistribution of immune subset profiles, and changes in other pharmacodynamic markers in the initial two patients treated in the ongoing study in patients with advanced breast cancer with bone metastases. The initial clinical data support the dual functionality of the compound and the potential of GMI1359 to enhance responses to chemo and immune therapies. This provides us with confidence that GMI1359, by potentially disrupting the tumor microenvironment, could be active across both liquid and solid tumors. That trial is continuing to enroll patients, and based on findings so far, we are evaluating indications for moving the program forward in the clinic. In the sickle cell setting, based on input from the FDA with respect to ribopanzole, as well as feedback from KOLs, we've previously reported to you we are focusing on the development of GMI1687. We have initiated IND enabling activities with treatment of acute vaso-occlusive crisis as a potential lead indication. This work continues toward a goal of initiation of phase one in the first half of 2022. We believe that GMI1687 may be ideally suited for this indication as it would enable patients to potentially self-administer treatment early in their crisis and reverse the underlying inflammatory cascade that's mediated by E-Selectin. Our earlier stage research efforts continue to progress particularly in the galactin field. Also at AACR, our research team presented new evidence on the effects of one of our galactin-3 antagonists in the pancreatic cancer model. The potency and selectivity of our compounds distinguishes us from competitive approaches, and we intend to roll out additional data as we move toward our goal of selecting a lead candidate for clinical development. Brian will now comment on our financial results.

Thank you, Rachel. As of June 30, 2021, glycomedics had cash and cash equivalents of $118.9 million as compared to $137 million as of December 31, 2020. Research and development expenses increased to $10.2 million for the quarter ended June 30, 2021 as compared to $9.9 million for the quarter ended June 30, 2020. This increase was primarily due to an increase in clinical trial costs in our ongoing global phase three clinical trial of upralesolan in individuals with relapsed refractory AML. General administrative expenses were $4.2 million for the second quarter ended June 30th, 2021 and 2020. I'd now like to turn the call back to Rachel.

Thank you, Brian. Before I open the lines to Q&A, I'd like to leave you with two takeaways. First, that we believe we are now less than six months from completing enrollment of our pivotal trial of upralesolan in relapsed refractory AML patients. This remains an area with high unmet need to improve clinical outcomes. Second, we've delivered on our promise to bring you news of newly initiated trials with independent investigators. We believe this speaks to the broad enthusiasm around the potential of upralesolin, and it also shows how we are laying a strong foundation for upralesolin in the hematologic arena. All of this speaks to the value of our glycochemistry platform, as we look forward to being in a position to share data with you in the future. I'd now like to comment on the other announcement we made yesterday that I'll be retiring from my role as CEO at Glycomimedics and that Herut Submergent will be taking over for me. Let me begin by sharing some personal reflections. As many of you know, I co-founded this company together with John Mignogne, our Chief Scientific Officer, 18 years ago. I feel very proud of what our team here at Glycomimedics has accomplished together. We have progressed the company from its early days as a venture-backed startup, through its initial public offering and multiple secondary offerings, through strategic partnerships, and the advancement into late stage development of two clinical candidates, each of which was discovered in our own labs. Our platform has been very productive, and we now have a pipeline of differentiated and exciting drug candidates that I hope and believe will make a difference in the lives of patients. I've loved this job. I've often reflected to friends and family how grateful I have felt that most of the days in my career I've come to work looking forward to what the day held, and at the end of the day, though sometimes tired, I have felt gratified by the opportunity to do such deeply meaningful work with colleagues I both like and respect. So why leave now? As I'm sure many of you will appreciate, demands on my personal life as well as my personal priorities have changed over the years. Our children are grown, but I now find myself spending more time addressing the needs of an aging parent who requires increasing care. In addition, my husband and I are new grandparents, and we see increased opportunities for time together with each other, as well as with our growing and extended family. This coincides with the time at GlycoMimetics, when if our Phase III trial is successful, the company looks to the potential to commercialize our first drug candidate. At such a time, it's exciting to bring in a CEO of the caliber of Harut Samarjan. Harut is an experienced oncology executive who's ideally positioned to lead the company going forward. Harout brings commercialization expertise that is spot on for what we need at the company in this phase. He has overseen several successful hematology oncology product launches, including preparation for the launch of Mitostarin in AML. During his 16-year tenure at Novartis, he held both strategic and operational roles in hematology and oncology. After that at Ipsen, he served as EVP and Chief Commercial Officer, where he was accountable for worldwide commercialization and portfolio strategy. Most recently, he served as CEO of Immunomedics before his sales to Gilead Sciences. Harut clearly brings the background and leadership experience that will no doubt serve us well. While it's hard for me to leave a job that I've loved, I know that the time is right in my personal life to make this change, and I'm confident that Harut brings just what the company needs. Harut will be taking the reins as CEO tomorrow, so he'll not be taking questions today. I do know that he looks forward to engaging with you not only in future earnings calls, but also at conferences and in one-on-ones. Today, I'd like to officially welcome him and offer him the chance to share some of his thoughts as he comes on board.

Ruth? Thank you, Rachel. Following in your footsteps is an honor, and I might add your accomplishments have set a high bar for your successor. I believe glycometics has exciting opportunities ahead. Your professor, Anne, is a differentiated drug candidate already recognized with breakthrough therapy designations from both the FDA and the Chinese regulatory authority. I'm confident, based on both preclinical and clinical evidence, that this drug candidate has potential for significant impact across the spectrum of AML. The enthusiasm of independent investigators, as well as the clinicians participating in our registration trials, provides a foundation for a successful commercialization plan, should the readout and regulatory interactions prove positive. While there are just a few glycobiology-based therapeutics on the market today, the field of glycobiology is rapidly advancing and ripe with opportunity. The science and technical expertise resident in glycomimetics underlines my confidence in the productivity of the platform. Across the pipeline, I'm seeing novel and potentially game-changing therapies. I look forward to working with the outstanding team at glycomimetics as we strive to make a difference in the lives of patients with cancer and other diseases. And of course, while it's early days to say that leave, I look forward to the opportunity to transition this company to a new focus on commercialization of drugs that will change patients' lives. Back to you, Rachel.

Thank you, Harut, and I want to extend to you my warmest welcome. I know GlycoMedix will be in good hands under your leadership. Operator, will you please open the lines for our Q&A session?

Ladies and gentlemen, as a reminder to ask questions, you will need to press star 1 on your telephone. Again, star 1. To withdraw your question, press the pound key. Please stand by while compiling the Q&A roster. Again, if you would like to ask questions, please press star 1. Your first question comes from the line of Ed White from HC Weinreich. Your line is open.

Good morning. Thanks for taking my questions. So maybe start off with a question for Brian. As far as SD&A and R&D go, they've been pretty steady over the last few quarters. I'm just wondering if the change in management will lead to any kind of significant one-time charges in the third quarter in SD&A. And then just on, you know, overall thinking about SD&A and R&D going forward, how should we be thinking about the cash runway?

Thanks, Ed. As far as one-time impact in Q3, we will see a slight increase in SG&A, but it'll be a non-cash expense. Other than that, we're still on track with the same forecast we've given in previous quarters. So current cash with current commitments gets us through Q1 of 2023. Okay, great.

Thank you, Brian. And then a couple of questions maybe for Rachel. I know it's tough to... to look at the timing of data from ISTs as they're out of your control, but how should we be thinking about how this data is released? Will this data come at medical conferences? Will you be putting them out in press release, or how should we be thinking about it, how we're going to find out about that data?

So, of course, as investigator-sponsored trials, the investigators will be leading the release of the data. But we do anticipate that that would generally come in the form of presentations at medical conferences. And obviously, as data is released at medical conferences, that would be paired with press releases from the company. So we'd expect those to be coordinated.

Okay, thank you. And then two other pipeline questions. When can we expect to see the next 1359 data And on 1687, just what are the final hurdles for filing the IND going forward? And how confident are you in that timing of the filing of the IND?

Sure. So in terms of 1359, I would expect that perhaps at the end of the year, we might see additional patients. The Duke site is continuing to enroll. As we've previously reported, that was a trial that's been affected by COVID since the patients are needing to come in for extra visits to the hospital in the context of that study, but I would expect that we may have additional data toward the end of the year. As far as 1687 is concerned, we're well on track with all of the standard things that are normally done for IND-enabling studies, making nice progress with toxicology, manufacturing, et cetera, and we're well on track to initiate enrollment of a Phase I study in the first half. I would add that we're particularly excited about that program given how the program was generally, we believe, de-risked by the data from the Rivet-Pansel trial with respect to both the value of targeting E-Select and NPAs of occlusive crisis and the value of getting on board early, both of which we think 1687 is well-positioned to achieve.

great thanks rachel and uh it's been a real pleasure working with you over the last few years and and just you know i want to send you you know all my best uh for your future thank you thanks a lot i did a pleasure working with you too and as a reminder i will be staying on the board and really look forward to doing all i can to continue to help glycomatics in any way that i that i can that's great thank you thanks again ladies and gentlemen

If you want to ask questions, please press star 1. Your next questions come from the line of Roger Song from Jefferies. Sir, your line is open.

Great. Thank you for taking the question. Just a quick one, also related to those IST data release. Since you're, of course, we know that the registration of study that's event driven and potentially those IST data will be released earlier than the pivotal study data. Just curious your thoughts, maybe Rachel or Eric, you can provide some insights regarding the research from those IST data to your registration of study data.

Sure. Let me make a couple of general comments about those as far as the data release. The two AML studies are both open-label studies, and so that does give an opportunity to follow them on an ongoing basis until the point where it's felt that the data set is meaningful enough to be released. The third study, the one that's being conducted in myeloma patients undergoing transplant, that is a randomized controlled trial. So in that case, the data release would wait until the study is fully enrolled and the blind can be broken. As far as read-through, I think I would simply comment that these are opportunities to take different looks at how the drug could work in other populations of AML patients. And I think both of the AML ISTs provide really excellent opportunity to potentially expand the value of that asset more broadly than simply the registration trials might allow us to do. And both of them follow strongly from the excellent scientific rationale that has been demonstrated through the preclinical data. So we think that they provide an important strategic opportunity to build on that scientific rationale and to expand the potential use of Eupraleslan.

Got it. Thank you. Uh, maybe, uh, yeah, another quick one for the enrollment for the registration study. Um, so you, you kind of maintain the guidance by the end of this year, but we also know the COVID kind of the Delta variants, all that kind of a different kind of a dynamic. So just curious, have you taken into account this new kind of a COVID situation? Also, we know lots of the AML patients in their inpatient setting. Uh, how did that impact to your, kind of a readout, if at all.

Yeah, so just looking back on the past on that trial, we did have a slowdown when COVID first hit last year for about a month or two. But after that time, the study enrollment rebounded. And since then, we've had very consistent momentum of enrollment. We're fortunate that we've been enrolling that study in multiple geographies. As a reminder, we're treating patients in Australia, in Europe, and in North America. So we've been able to mitigate some of that risk by treating patients in different geographies. And we've had very consistent momentum of enrollment since the middle of last year. So now where we're close to completion of enrollment, we do expect and certainly we hope and expect that we'll be able to complete by the end of the year. But we have not seen a drop-off in momentum in the past couple of months. As you point out yourself, the patients are inpatient. The other thing that's important about the trial that we think has benefited enrollment in this, even in the COVID setting, is that because patients have acute leukemia, the acute treatments can't be delayed, and the uprolethylamine is added on top of the normal standard of care, so the patient is not asked to have, you know, substantive additional interactions with the healthcare system through enrollment with this study. So we think that those factors have supported the ongoing momentum and To date, we've not seen a reduction in that momentum as a result of the Delta variant.

Got it. Thank you. Also, as my kind of the sentiment, they're retiring and they're really having a pressure with working with you in the past. Thank you.

Thank you.

Thanks, Roger. There are no further questions at this time. Ms. Rachel, please continue.

Thank you. Well, so to conclude, I want to say that I'm deeply grateful for my time at Glycomimedics and for the opportunity to work with the talented and dedicated people here. I know that Harut and the rest of the team here will continue to make great progress during this exciting time for Glycomimedics. I very much look forward to supporting him and the company however I can as a member of the board and as an advisor during the transition. And thank you all for joining us today.

Ladies and gentlemen, thank you for participating in today's conference. This concludes today's program. You may now disconnect. Everyone, have a great day.