Crescent Biopharma Inc (CBIO) 2022 Q3 法說會逐字稿

Good morning, and thank you for joining the GlycoMimetics’ Q3 2022 Earnings Call. (Operator Instructions)

I would now like to turn the call over to Christian Dinneen-Long, the Company Counsel at GlycoMimetics. Please go ahead.

Good morning. Today, we will review our business updates and financial results for the quarter ended September 30, 2022. The press release we issued this morning is available on the company's website at 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 the 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 over to 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.

Thank you, Christian, and good morning, everyone. This past quarter, we made substantial progress with our pivotal Phase III 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're 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 III study protocol. We believe this interim utility analysis to 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 follow-up data from previous AML trials. 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 1 year ago this same week. And as we announced in our second quarter earnings call, the Phase III population is broadly similar to that of our completed Phase I/II study with respect to age, severity of AML, prior stem cell transplantation rates and distribution of relapsed and refractory patients, which taken together gives us confidence that we recruited the appropriate patient population.

The Phase III study is slower accumulation of blinded pooled survival events prompts us to extend the overall survival event trigger projection for final analysis from midyear 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 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 unblinding 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 the 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 3 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 III 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 III, 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. 2 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 detail.

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 was 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 suffered dismal outcomes. After frontline therapy, about 70% of newly diagnosed patients relapse within 3 years, 5-year survival languishes at 29%. Despite introduction in the last 5 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 block 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 III 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 the 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 5 and 7 months. The target survival hazard ratio in our Phase III 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. 2 recent AML trials that did meet their primary survival endpoints had notably higher median follow-up duration at the time of analysis. Astellas' Phase III ADMIRAL trial showed gilteritinib superiority over salvage chemotherapy in FLT3-positive relapsed and refractory AML at 18 months of median follow-up.

And Jazz' Phase III study showed CPX-351 superiority over 7+3 chemotherapy in secondary AML at 21 months of median follow-up. Median follow-up 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 follow-up duration at time of analysis of more than 30 months, more than 30 months, that number is unprecedented for follow-up 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 2-sided 0.045 million. 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, it's 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 2 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 Jones of the University of California, Davis, will present preliminary results from his Phase I 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 8 evaluable patients as well as 67% MRD negativity among the responders with complete responses or CRs

Additionally, Dr. Manuel Alfonso Fuente will present results from preliminary results from the first 10 patients of a Phase Ib/II 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 5 months. We're 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 combined ability 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 nm 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 II portion of this Phase II/III trial completed enrollment of 260 patients in November 2021, 1 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 NCI's Phase II interim analysis and whether the trial will reopen for Phase III. 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 II analysis is independent from that of our pivotal Phase III 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.

Thank you, Ed. As of September 30, 2022, GlycoMimetics had cash and cash equivalents 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 2 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 III relapsed/refractory AML clinical trial to follow up. completion of key Ulsan 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 precommercial 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 for the same period in 2021.

Decreased expenses were primarily due to lower global Phase III 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.

Thank you, Brian. As today's update demonstrates, this is a very exciting time for us at GlycoMimetics. Given longer blinded pooled survival than expected in our Phase III 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 III 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 towards 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?

Thank you. At this time, we will conduct the question-and-answer session.

(Operator Instructions)

Our first question comes from Ed White at H.C. Wainright.

Regarding the potential IDMC meeting and determination in the first quarter of '23, perhaps you can just discuss potential regulatory time and development time line following that data if it is positive.

Yes. Good to hear your voice. So as we said, the -- we anticipate the independent data monitoring committee to meet by end quarter 1 to really discuss one of 2 possibilities with this utility interim analysis. We either continue the trial as planned to the 100% events, which currently we anticipate we moved that date from midyear 2023 to around year-end 2023. Or if there's compelling efficacy seen by the IDMC, then they will recommend the company the stopping of the trial and the immediate unblinding of the trial.

To your question, Ed, what happens then? Obviously, we're very committed. If whenever that for data happens to be that the interim analysis or by the year-end, Remember, we have fast-track orphan designation, and we're already discussing with the FDA, as you've seen as part of our interim analysis. So we want to make sure that we are -- 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.

Okay. 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.

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 where we're moving forward in the U.S., then we will just 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.

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 planned 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 you for last one.

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 file 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 could see something in 2023?

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 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 parallel to that is the NCI trial in the frontline setting. These are both registrational great 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 population. 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 be the first indication of relapsed/refractory.

Great.

Does that to help, Ed.

It does. Thank you very much.

Thank you.

(Operator Instructions)

As there are no more questions, I'd like to hand the call back to Mr. 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.

That concludes today's call. You may now disconnect. Thank you.