GlycoMimetics, Inc. (NASDAQ:GLYC) Q3 2022 Earnings Conference Call November 9, 2022 8:30 AM ET
Company Participants
Christian Dinneen-Long – Company Counsel
Harout Semerjian – President and Chief Executive Officer
Brian Hahn – Senior Vice President and Chief Financial Officer
Bruce Johnson – Senior Vice President and Chief Commercial Officer
Edwin Rock – Chief Medical Officer
Conference Call Participants
Edward White – H.C. Wainwright
Operator
Good morning and thank you for joining the GlycoMimetics Q3 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.
Christian Dinneen-Long
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 website @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; Dr. Ed Rock, Chief Medical Officer; and Bruce Johnson our Chief Commercial Officer. We will start today’s call with comments from Harout, who will provide a broad overview of the business and updates on uproleselan development program, followed by Ed with additional commentary on uproleselan clinical studies, including both company and investigator sponsored trials. Brian will then provide details on the company’s financial position, before we 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 candidate, uproleselan and our other pipeline programs, along with expectations regarding our operations, cash position, and the conduct of or data from clinical trials, as well as planned or potential development, regulatory interactions or submissions, and pre-commercialization activities and 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 our filings with the SEC, which are available from the SEC or on our website.
I’ll now turn the call over to Harout.
Harout Semerjian
Thank you Christian and good morning everyone. This past quarter, we made substantial progress with our pivotal Phase 3 trial of uproleselan in combination with chemotherapy in patients with relapsed, refractory, acute myeloid leukemia and we further strengthened our foundation in line with our goal to become a commercial stage company.
We are particularly excited to share with you today that the U.S. Food and Drug Administration recently cleared the addition of an Interim Utility Analysis to our uproleselan Phase 3 study protocol. We believe this Interim Utility Analysis should be essential given that the blinded pooled patient population in our study is living longer than expected.
As part of our decision, we conducted careful analysis of the followup data from previous AML, we engaged in multiple discussions with medical experts, and we met with the FDA in order to validate our plan. As a reminder, we completed enrollment of our pivotal trial one year ago this same week, and as we announced in our second quarter earnings call, the Phase 3 population is broadly similar to that of our completed Phase 1/2 study with respect to age, severity of AML, prior stem cell transplantation rates and distribution of relapse and refractory patients, which taken together gives us confidence that we recruited the appropriate patient population.
The Phase 3 study is slower accumulation of blinded pooled survival events prompts us to extend the overall survival event trigger projection for final analysis from mid-year 2023 to around year end 2023. Simultaneously, we see an ethical need for this interim analysis to address the possibility that this slowdown in patient events may relate to benefit from uproleselan study therapy.
As part of the interim analysis, the study’s Independent Data Monitoring Committee or DMC is expected to meet by the end of Q1 2023. They will consider whether to continue to the original a 100% overall survival events trigger, or if the efficacy data for treatment with uproleselan in combination with standard chemotherapy is observed to be compelling, they’ll recommend immediate un-blinding and trial analysis completion. We owe it to AML patients to assess the drivers for slower accumulation of blinded, pooled survival events in this disease, which remains one with high unmet need and limited treatment options.
Importantly, this interim analysis preserves 95% of the original designs alpha and enables us to maintain the study blind if the Independent DMC recommends continuation to final analysis. Regardless of whether the DMC’s recommendation enables us to expedite registrational filings or we continue to study as originally planned, we are excited by uproleselan’s potential to improve outcomes in relapsed, refractory AML and help patients achieve deeper, more durable remissions that bridge them to potential curative stem cell transplantation and improve overall survival.
From a commercialization standpoint, we continue to focus on three key areas. First, to drive awareness and educate medical experts on E–selectin biology in AML and uproleselan’s unique and differentiated mechanism of action. Second, to drive awareness of uproleselan’s clinical development program, and third, to expand our partnership with global medical community. Bruce Johnson, our Chief Commercial officer, will be available for Q&A to discuss these ongoing efforts, which we expect to position us well as we approach key Phase 3 milestones.
Overall, the third quarter marked a period of significant progress, and steady execution for GlycoMimetics. We have the team in place to advance uproleselan and deliver the therapy to patients who need it. I’m pleased to be joined on this call by Dr. Ed Rock, who we welcomed to GlycoMimetics just a few short months ago as our Chief Medical Officer. He will provide additional context on our Phase 3, how it compares with other historical large randomized AML trials and how this comparison reinforces our confidence in uproleselan’s potential to address significant unmet need for more effective AML therapies.
Ed will also share updates on investigator sponsored uproleselan trials. Two posters will be presented at the upcoming American Society of Hematology Annual Meeting that represent the first clinical data presentations for this therapy outside of company sponsored trials. These posters provide support for our belief in the potential broad utility of uproleselan across the AML spectrum from treatment naive to notoriously unresponsive treated secondary disease.
Ed, I’ll pass it on to you to share more details.
Edwin Rock
Thanks Harout, and thanks to everyone for joining our call today. Let me begin with how uproleselan could fit into the AML treatment landscape. As a reminder, AML is the second most common type of leukemia and the highest cause of death among all patients with leukemia. About 55,000 people in the U.S. are now living with AML and more than 20,000 adults are diagnosed annually.
People with AML suffer dismal outcomes. After frontline therapy about 70% of newly diagnosed patients relapse within three years. Five-year survival languishes at 29%. Despite introduction in the last five years of several new therapies, high unmet medical need persists given AML’s heterogeneity and drug resistance.
Uproleselan is our investigational, first-in-class E–selectin antagonist. E–selectin mediates myeloid cell attachment to blood vessels, regulates their survival and thus contributes to chemotherapy resistance. Uproleselan blocks cancer cells from binding to E–selectin on blood vessels and thus interrupts the pro-survival signal conferred by E–selectin binding. We believe that by targeting this novel carbohydrate recognition mechanism, uproleselan will disrupt leukemic cell drug resistance and potentially improve outcomes for patients with this devastating disease.
As Harout explained, in our pivotal Phase 3 study of uproleselan in relapsed and refractory AML, blinded pooled survival events show that people in this trial are living longer than would be expected based on historical benchmarks. As such, we approached FDA in late summer about adding an interim analysis to assess whether this slow survival event accumulation relates to uproleselan study treatment and uproleselan benefit. The FDA cleared our plan at a meeting earlier this fall.
Interim analysis will occur once about 80% of original planned events are observed. The study’s Independent Data Monitoring Committee is expected to meet by the end of Q1, 2023 to consider whether to continue to the original 100% OS events trigger or alternatively to recommend immediate and complete trial analysis if efficacy data from study treatment with uproleselan plus standard chemotherapy is observed to be compelling.
Recent overall survival benchmarks in relapsed and refractory AML are between five and seven months. The target survival hazard ratio in our Phase 3 study is 0.68. That represents a 32% reduction in risk of death at any point in time. Regulators, patients, and clinicians, have agreed that this level of survival prolongation is significant and clinically meaningful.
In contrast to recent trials in relapsed and refractory AML that failed to show improved survival over cytarabine alone, two recent AML trials that did meet their primary survival endpoints had notably higher median followup duration at the time of analysis. Astellas’ Phase 3 ADMIRAL trial showed gilteritnib superiority over salvage chemotherapy in FLT3 positive relapsed and refractory AML at 18 months of median followup. And Jazz’s Phase 3 study showed CPX-351 superiority over 7+3 chemotherapy in secondary AML at 21 months of median followup.
Median followup in our uproleselan study was 19.5 months as of September, 2022. Based on the time course of events to date, another 15 months is now projected for accumulation of sufficient survival events to trigger the original protocol specified analysis. Should the events trigger extend to around year end 2023, that would mean median followup duration at time of analysis of more than 30 months, more than 30 months. That number is unprecedented for followup duration in a trial of novel relapsed and refractory AML therapy.
If interim analysis demonstrates compelling evidence of benefit from addition of uproleselan to AML therapy, then we want to recognize that benefit as soon as possible in order to accelerate product availability to all eligible patients with relapsed and refractory AML. Alternatively, if the DMC recommends we continue the study through the full survival events trigger, expected around the end of 2023, we remain confident that events reflected in the original study design may still illustrate substantial patient benefit of uproleselan study therapy.
Interim analysis will spend less than 5% of total alpha allocated to the primary endpoint. That translates to a final analysis P value of 0.048 instead of the original two sided 0.045. Alpha spend within interim analysis is intentionally conservative in order to ensure that any conclusion of benefit would be based on compelling evidence of benefit.
If this high stringency threshold for declaring a positive trial is not met at interim analysis, then about 95% of alpha remains for the final survival analysis described in the original protocol, roughly the same as the original planned final analysis. Whether the DMC’s recommendation enables us to expedite registrational filings or we continue the study as planned through the full survival event trigger, we remain excited by uproleselan’s potential to improve outcomes in relapsed and refractory AML.
Separately, we’re pleased that results from two investigator sponsored trials of uproleselan will be presented at the upcoming ASH Annual Meeting. These trials are exploring uproleselan’s potential to benefit patients with AML beyond those with relapsed, refractory disease alone. Dr. Brian Jonas of the University of California Davis will present preliminary results from his Phase 1 study that indicates a tolerable safety profile of uproleselan with azacitidine and Venetoclax in people with untreated AML who are unfit for intensive chemotherapy.
In addition to encouraging safety, this combination also shows encouraging evidence of disease activity, including an overall 50% rate of MRD negativity in eight evaluable patients, as well as 67% MRD negativity among the responders with complete responses or CRis. Additionally, Dr. Emmanuel Almanza-Huante will present preliminary results from the first 10 patients of a Phase 1b/2 trial showing that uproleselan with cladribine plus low-dose cytarabine was similarly well tolerated. This combination produced an overall response rate of 62% in a very high risk population of treated secondary AML patients having expected median survival of less than five months.
We are grateful to the clinician scientists running these ISTs for their dedication to exploring potential benefits of uproleselan in patient populations with high unmet need. Also, we appreciate and thank the patients that have consented to testing investigational uproleselan. These presentations are the first clinical uproleselan data generated outside of company sponsored trial, trials in relapsed-refractory and frontline fit patients.
Despite limited numbers, these data provide support for our belief in the potential broad utility of uproleselan across AML disease indications, and these data demonstrate combinability with other available therapies as well as evidence of a favorable safety profile without dose limiting toxicities. We look forward to sharing more about these studies at ASH in December.
Beyond the studies described, 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 addition of uproleselan to a standard 7+3 regimen in older adults, leads to improved outcomes. The Phase 2 portion of this Phase 2/3 trial completed enrollment of 260 patients in November, 2021, one year ago. For the protocol, NCI has suspended further enrollment in anticipation of its planned interim analysis of event free survival. When available, we intend to share the outcome of the NCIs Phase 2 interim analysis and whether the trial will reopen for Phase 3.
This NCI trial gives us another opportunity to confirm uproleselan benefit and potentially to expand our label to include frontline AML. Importantly, the outcome of NCI’s Phase 2 analysis is independent from that of our pivotal Phase 3 study in relapsed refractory AML and thus provides an additional near-term opportunity for uproleselan beyond that in relapsed and refractory AML.
Now, I’ll hand it over to Brian for an overview of financial results.
Brian Hahn
Thank you, Ed. As of September 30, 2022, GlycoMimetics had cash and cash equivalence of $51.6 million as compared to $90.2 million as of December 31, 2021. Q3 cash burn slowed to $8.6 million as compared to $30.1 million over the first two quarters of 2022. We expect our current cash resources will fund our operations to the end of 2023 as a result of a decrease in expenses driven by the transition of the Phase 3 relapsed refractory AML clinical trial to follow up, completion of key uproleselan commercial manufacturing activities, and realization of savings from the headcount reduction in the first quarter of 2022.
Allocation of resources will continue to prioritize the advancement of the uproleselan development program, including key regulatory and pre-commercial activities. The company’s research and development expenses decreased to $4.9 million for the third quarter ended September 30, 2022 as compared to $13.3 million to the same period in 2021. Decreased expenses were primarily due to lower global Phase 3 clinical trial and development costs as patients enrollment ended in November, 2021.
The company’s general and administrative expenses decreased to $3.8 million for the quarter ended September 30, 2022 as compared to $4.1 million for the third quarter of 2021, primarily due to lower professional fees.
I’d now like to turn the call back to Harout.
Harout Semerjian
Thank you, Brian. As today’s update, demonstrate this is a very exciting time for us at GlycoMimetics. Given longer blinded pool survival than expected in our Phase 3 study we look forward to conducting this analysis, this interim analysis. Regardless of whether the interim analysis demonstrates that the data is compelling enough to expedite registrational filings or we continue the study as planned through the finer overall survival events trigger, we’re confident and excited about the potential for uproleselan to improve outcomes in the relapsed refractory AML and remain committed to bringing this product to market as quickly as possible.
We’re proud of our sustained clinical progress, not just in this pivotal Phase 3 study of uproleselan in relapsed refractory AML, but also in the ISTs that Ed just described. Though these are preliminary results from a limited number of patients, they continue to illuminate uproleselan’s encouraging potential in additional important AML patient populations.
In parallel with these clinical activities, our experienced commercial team, led by Bruce, continues to prepare our organization to successfully deliver uproleselan to patients if approved. These exciting advancements position us well to continue working toward our goal of improving the lives of patients with cancer and inflammatory diseases, and we look forward to sharing updates with you on future calls.
I’d now like to open the lines for questions. Operator?
Question-and-Answer Session
Operator
Thank you. [Operator Instructions] Our first question comes from Ed White at H.C. Wainwright. Ed, your line is open.
Edward White
Good morning. Thanks for taking my questions. Regarding the potential IDMC meeting and determination in the first quarter of 2023, perhaps you can just discuss potential regulatory time and development timelines following that data if it is positive?
Harout Semerjian
Yes. Good morning, Ed. Good to hear your voice. So as we said the, we anticipate the Independent Data Monitoring Committee to meet by end quarter one to really discuss one of two possibilities with this Utility Interim Analysis. We either continue the trial as planned at the 100% events, which currently we anticipate, we move that date from mid-year 2023 to around year end 2023 or if there’s compelling efficacy seen by the IDMC, then they will recommend to the company the stopping of the trial and the immediate un-blinding of the trial.
To your question, Ed, what happens then? Obviously, we’re very committed if whenever that – the data happens, be it at the interim analysis or by the year end, remember we have Fast Track Orphan Designation and we are already discussing with the FDA as you’ve seen as part of our interim analysis. So we want to make sure that we’re as part of that, Fast Track and of course the Breakthrough Designation, we rapidly move forward with our regulatory pathway and our regulatory team is really ready and waiting for that moment to happen Ed, so stay tuned.
Edward White
Okay, thanks. And you did a good job discussing the potential opportunity in the U.S. How should we be thinking of potential opportunities outside the U.S.?
Harout Semerjian
Yes of course, I mean, we’re first focusing on the U.S. and given it’s the largest market with the largest opportunity and the first one, obviously, but at the same time Ed as a reminder for everyone, our trial is well balanced in its enrollment between the U.S. and ex-U.S. So we have significant presence as well in terms of patient enrollment and medical activities, ex-U.S. as well. So the plan would be, the moment we’re moving forward in the U.S. then we will focus on ex-U.S. But maybe Bruce, do you want to add a couple of maybe thoughts or color for Ed of some of the activities ex-U.S.?
Bruce Johnson
Yes, thank you, Ed. I mean, we’re continuing to engage medical experts around the globe. We’re getting very encouraging feedback on their reception of the data thus far in our current development program. As Harout mentioned, we do have ongoing discussions with regulatory authorities in Europe and fully plan to pursue registration in a variety of major markets around the globe. I would say also with that, we are keeping all options on the table, certainly as well as, certainly potential partnerships, et cetera. But we’re exploring all options as we look at the opportunity for uproleselan.
Edward White
Thanks. And perhaps the last question if I may, just regarding the ISTs, how should we be thinking about the potential there for the company to follow suit and look at these potential indications? Will you be waiting to well after potential approval or is this something that you’re looking at now and perhaps we can see something in 2023?
Harout Semerjian
Yes, so basically what we’re doing Ed, as a reminder for everyone, we’re pursuing, we believe that uproleselan has a role to play across all populations in AML, from the naïve, treatment naive to the really difficult to treat secondary AML. So the plan is to really make sure that from a regulatory pathway, we pursue our pivotal trial in relapsed refractory AML. So that’s really our big anchor. And additional peril to that is the NCI trial in the frontline setting. These are both registrational grade trials, that are moving and advancing and maturing, the data is maturing as we speak.
And then you have these additional ISTs that really supplement the understanding of the role of uproleselan across different AML subpopulations. Remember, these are populations that are all, I would say, have a high unmet medical need at different levels. And there is an opportunity to pursue the addition of uproleselan to other standard therapies because we believe with the low toxicity profile of uproleselan, and if it’s able to generate additive efficacy, then it has the potential to really be adopted across all AML populations.
So the whole idea is first we pursue our pivotal trials. Obviously we want to make sure we get to market, but then as the data is emerging, there is a significant opportunity to really advance the clinical development program with uproleselan beyond what will possibly the first indication of relapsed refractory.
Edward White
Great.
Harout Semerjian
Does that help Ed?
Edward White
It does. Thank you very much.
Harout Semerjian
Thank you.
Operator
[Operator Instructions] All right. As there are no more questions, I’d like to hand the call back to Mr. Semerjian.
Harout Semerjian
Thank you, Operator. Thank you to everyone for joining our call today. We will also be presenting at several upcoming investor conferences, including Stifel and Jefferies in London this month. We look forward to speaking with many of you then. Thank you very much. Back to you operator.
Operator
That concludes today’s call. You may now disconnect. Thank you.
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