GlycoMimetics Inc (GLYC) 2018 Q4 法說會逐字稿

Good morning, and thank you for -- thank you all for joining the GlycoMimetics call. (Operator Instructions)

I would now like to turn the call over to Shari Annes of the Investor Relations group at GlycoMimetics. Please go ahead.

Good morning. Today, we will highlight the key achievements of 2018, provide a summary of our financial results for the year-end and comment on the milestones we anticipate in the next few months. The press releases we issued this morning on our year-end and Q4 financials and yesterday on our board transition are available in the News section of the company's website at www.glycomimetics.com.

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 in the Investor Relations section of the company's website for 30 days.

Joining me on the call today from GlycoMimetics are Rachel King, Chief Executive Officer; Brian Hahn, Chief Financial Officer; and Dr. Helen Thackray, Senior VP of Development and Chief Medical Officer.

We will start today's call with comments from Rachel, and after that, Brian will provide an overview of the company's financial position. We will then open the call for Q&A. I'd like to remind you that today's call will include forward-looking statements based on current expectations. Forward-looking statements contained on this call include, but are not limited to, statements about the development plan for uproleselan, formerly known as GMI-1271; and for rivipansel, GlycoMimetics' product candidate licensed to our collaborator, Pfizer; and as well as our other pipeline programs. 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 statements. Please refer to GlycoMimetics' filings with the SEC, which are available from the SEC or on the GlycoMimetics website, for information concerning the risk factors that could affect the company.

I'd now like to turn the call over to Rachel.

Thank you, Shari, and thank you all for joining our call. This morning, I'd like to cover 3 topics: first, the upcoming Phase III results for rivipansel in patients experiencing sickle cell crisis; next, the major accomplishments of 2018; and finally, the milestones we expect to achieve in the coming months.

I believe we're poised for important accomplishments in 2019, all of which were made possible by the achievements of last year. As you may recall, Pfizer has said they intend to announce top line results from the Phase III reset trial of rivipansel at the end of the second quarter this year. The anticipated timing of this readout has not changed. With less than 4 months until the Phase III readout, our enthusiasm is high. The Phase III readout is an important milestone that very few drugs in development reach.

Since our discovery of rivipansel, we've focused chemistry, preclinical and clinical development resources to derisk and advance the program. Today, we believe we're on the cusp of delivering a potential therapy for sickle cell crisis that could transform the way patients with this devastating disease are treated. This has been our goal for the program since its inception.

While the pivotal data will tell the ultimate story, we do believe that the rivipansel study has a high probability of success and, if positive, that this novel on-demand agent could be utilized extensively in the major markets.

We base this confidence on a number of factors: First, the data from our own Phase II trial, which, among other things, demonstrated an 83% reduction in opioid use throughout the duration of hospitalization, a finding that gives us confidence that the drug is having its intended biological effect. Second, the fact that selectin inhibition has now been clinical validated as a therapeutic target based on data from our controlled trial as well as other programs that have demonstrated that selectin inhibition can reduce the incidence of VOC. Third, the sample size and powering of the reset trial, which includes 350 patients, approximately fourfold larger than our Phase II trial, we believe this more than adequately powers the trial to demonstrate the statistically significant result on the primary end point as well as on key secondary end point. The fact that this is the only on-demand therapy for sickle cell crisis that is in late-stage development and also importantly, the subject of a special protocol set by the FDA, that's the fourth reason. And finally, last but not least, as part of the Phase III program, clinical and pharmacoeconomic outcomes are being rigorously assessed, allowing this data to serve as the basis for regulatory pricing and reimbursement discussions. We believe that reducing the hospital stay would be meaningful to patients, physicians, regulators and payers. Furthermore, we expect this clinical benefit along with reductions in opioid use to strongly position rivipansel for regulatory and commercial success.

As you can imagine, rivipansel's market potential was a key consideration as we began our work in sickle cell disease, but commercialization and details of market planning are now Pfizer's responsibility. So I'd like to reiterate Pfizer's recent public statements describing rivipansel as a potential blockbuster. They estimate possible annual peak sales of greater than $1 billion.

What would a positive outcome in the Phase III rivipansel trial mean for us? First and foremost, we would be deeply grateful if we can contribute to transforming and improving the lives of people with sickle cell disease. That would be personally meaningful to each of us, and it's been a long-time goal of ours that has been motivating us since the program began.

Second, a successful outcome with rivipansel, a drug discovered, synthesized and developed through Phase II by GlycoMimetics, would serve as validation for our unique glycomimetic discovery platform. In particular, it would confirm the value of targeting selectins and our ability to translate our understanding of carbohydrate chemistry into novel therapeutics. We believe this would reinforce our leadership in the field of glycobiology, an emerging space and an untapped source of novel therapeutics.

Third, I like to remind you of the potential financial benefits to GlycoMimetics. Under our agreement with Pfizer, GlycoMimetics is entitled to receive development, regulatory and commercial milestone payments of up to $285 million in the aggregate, with the next milestone payment due to us on acceptance of an NDA. After that, we're entitled to a further milestone payment upon the first commercial sale in the United States. We're also eligible for similar regulatory and commercial milestone payments based on progress in the EU.

The royalties are also healthy and based on rivipansel product sales. They begin in the low double digits and go to the low teens. The very meaningful milestone payments, together with potential royalties from sales of the drug, would allow us to accelerate the development of our novel GlycoMimetics pipeline.

I'd now like to recap the achievements of 2018. If there's one overriding theme that characterizes our focus and progress, it is execution, execution across all fronts: clinical, preclinical and financial. Our wholly owned investigational drug for AML, uproleselan, reflects once again the commitment of our cross-functional teams in chemistry, preclinical, and importantly now, focusing in clinical development.

Early last year, we announced a comprehensive Phase III clinical program in AML. Our vision for uproleselan is to position it as a foundational therapy that could work across the AML spectrum whether a patient has relapsed/refractory disease, is newly diagnosed and fit for chemotherapy or not fit for chemotherapy. Based on the strength of the clinical data, we opted to move forward on a company-sponsored pivotal trial in the relapsed/refractory setting, which is the indication where we have the breakthrough therapy designation. And in early November, we announced the dosing of the first patient in that Phase III study. That trial is now well under way with good enrollment momentum.

In parallel, we announced collaborations with 2 consortia, one here in the U.S. with the Alliance for Oncology and National Cancer Institute and one in Europe with the prestigious HOVON group to study uproleselan in 2 additional patient populations. The NCI study is active and open for enrollment with dosing of a first patient expected in the next quarter.

In December, at the annual ASH meeting in San Diego, we reported in an oral presentation final Phase I/II data that included extended follow-up for survival in patients in both relapsed/refractory and the newly diagnosed population. This data has increased our confidence in the key efficacy end points that underpin our GMI and NCI-sponsored registration programs.

Importantly, we also presented for the first time data on measurable residual disease, or MRD. Over 50% of the evaluable patients in both the relapsed/refractory and newly diagnosed cohorts achieved the stringent level of disease response. We believe uproleselan selectively disrupts the relationship between leukemic cells and the bone marrow microenvironment. Therefore, we had hoped to see a higher percentage of those patients who achieved complete remission to be MRD negative. That's exactly what we saw, and this finding suggests that uproleselan is indeed enhancing the depth of remission.

I'd also like to remind you of the trial's correlative data on E-selectin ligand expression on leukemic blasts and leukemic stem cells. That data showed our target to be highly relevant particularly in the relapsed/refractory population with higher levels of E-selectin ligand expression correlating with both response and survival in this cohort of patients treated with uproleselan. In short, the data on expression, combined with the data on MRD negativity, further support our underlying hypothesis that E-selectin is a driver of resistance in AML. If we can disrupt binding of cancer cells to this target, we believe the result will be improved clinical outcomes.

Across our GMI-sponsored, NCI-sponsored and HOVON-sponsored program, we expect to have over 850 patients treated in Phase II/III clinical programs evaluating uproleselan in North America, Europe and Australia. If the results from each of these studies are positive, we expect that the totality of the data could support a broad label across the continuum of care in AML.

I'd now like to spend a few moments highlighting the significant progress we've made in discovery research and preclinical, the result of which is a robust pipeline of novel agents, all of which come from the specialized chemistry expertise that underlies our glycomimetic discovery platform here at the company.

In December, we presented data on 2 compounds -- 2 new compounds: GMI-1687 and GMI-1757, which both had their debut in the public arena at ASH. Of particular note, our poster on GMI-1687, a highly potent antagonist of E-selectin, points to the potential of GMI-1687 as an important follow-on drug candidate to uproleselan, with the potential advantage of self-administration in the outpatient setting. We believe this could enable us to realize the value of an E-selectin antagonist outside of AML.

Our poster on GMI-1757, a novel dual-function Galectin-3/E-selectin antagonist, shared data on the first of a series of Galectin-3 antagonists, which we believe could have broad applicability in a variety of cancers and fibrotic conditions. We'll be rolling out more preclinical data with these agents as well as other Galectin-3 antagonists in 2019. We're proud of the platform developed here and excited about the opportunities that these novel drug candidates represent.

One final comment. We were pleased in the third quarter to receive a patent issuance for uproleselan in Japan. This patent covers composition of matter as well as pharmaceutical formulations and expires in December 2032. This patent extends intellectual property coverage for uproleselan across all 7 of the major markets, and it solidifies an important component of our continually expanding intellectual property portfolio.

At this time, I'd like to look forward across 2019 to the milestones we anticipate. In the second quarter of this year, we expect to announce dosing of the first patient in the NCI-sponsored Phase III trial on AML patients who are newly diagnosed and fit for chemotherapy. Later this year, we also expect to announce the initiation of the HOVON-sponsored trial in patients with newly diagnosed AML who are unfit for intensive chemotherapy.

As highlighted in the beginning of this call, at the end of the second quarter, we're expecting to announce top line data from the Phase III pivotal trial of rivipansel in sickle cell disease. Again, we believe a positive outcome will transform the way patients with sickle cell disease are treated as well as bring other tangible and intangible benefits to our organization.

Later this year, we also expect to be in a position to announce the initiation of an exploratory clinical trial of GMI-1359 in a solid tumor indication. We've continued to make progress with this drug candidate and have decided to move into a solid tumor setting in which we will be able to evaluate biomarker and PK data in patients with cancer that has metastasized to bone. We'll be providing additional details about this trial later in the year, and this will be our first trial with our potent dual-function antagonist in cancer patients.

Finally, before turning the call to Brian for a review of our financials, we issued a board release yesterday in parallel with the filing of our proxy that the Chairman of our Board of Directors, Jim Barrett; and our Chief Scientific Officer, John Magnani, will not be returning for reelection to the board when their terms expire later this year.

Jim, since 2001, was a general partner at NEA. He led NEA's founding venture investment in our company, and as a representative of GlycoMimetics' largest shareholder, has chaired our board since its founding. His decision not to run for reelection comes at a time when he's announced his retirement both from NEA and from a number of boards. We are all deeply grateful to him for the support and guidance he's provided through the years.

John Magnani, as many of you know, co-founded GlycoMimetics with me and has been our Chief Scientific Officer since the company's inception. He remains in that position even with the transition from Board Director. All of the work here at GlycoMimetics is a product of a specialized chemistry platform for which John has provided exceptional creativity and leadership. His key position on our senior leadership team does not change with this announcement.

Stepping into the role of Board Chair will be Tim Pearson, a GlycoMimetics Director since 2014, and until recently, Chief Financial Officer and Executive Vice President for TESARO. This change will be effective at our annual meeting of stockholders on May 17. Tim brings broad industry experience from his senior roles at a number of leading biotech companies, and we very much look forward to working with him as our Chair. I might add we have an impressive Board of Directors here at GlycoMimetics and these changes are part of a natural maturation process.

Let me now turn the call over to Brian, who will review our financials with you. Brian?

Thank you, Rachel. As of December 31, 2018, GlycoMimetics had cash and cash equivalents of $209.9 million compared to $123.9 million as of December 31, 2017. The company in the first quarter of the year successfully completed a follow-on public offering, netting proceeds of $128.4 million. The company's research and development expenses increased to $12 million for the quarter ended December 31, 2018, as compared to $6.7 million for the fourth quarter of 2017.

Research and development expenses increased by $16 million to $40 million for the year ended December 31, 2018, from $24.1 million in the year ended December 31, 2017. These increases were primarily the result of higher manufacturing costs to scale up production of uproleselan and clinical supplies for the company's Phase III clinical trial and for clinical trials conducted by or in collaboration with third parties.

Personnel-related and stock-based compensation increased due to an increase in clinical head count. The company's general and administrative expenses increased to $2.9 million for the quarter ended December 31, 2018, as compared to $2.8 million for the fourth quarter of 2017. General and administrative expenses for the year ended December 31, 2018, increased to $11.4 million as compared to $9.8 million in the prior year. These increases were primarily due to an increase in legal and patent expenses as well as personnel-related costs and stock-based compensation expense.

Patent expenses were higher due to an increase in the number of patent applications filed. Personnel-related and stock-based compensation expenses increased due to additional head count in 2018.

In summary, GlycoMimetics is in an excellent financial position to carry out its planned initiatives and to advance applications for its unique technology platform.

I'll now turn the call back over to Rachel.

Thank you, Brian. I hope you'll agree that we've been uniquely successful in progressing truly differentiated drug candidates from discovery well into late-stage development. Starting with rivipansel pivotal results at the end of the second quarter of this year, we now anticipate what we hope will be a series of value-creating milestones, which I hope will reward patients and their shareholders for years to come.

With that, I'd like to open the call for your questions. Operator?

(Operator Instructions) Our first question comes from the line of Jotin Marango of ROTH Capital.

Two questions, first about upro. I know it's certainly early -- it's still early in the process, but do you have any qualitative commentary or side feedback about the enrollment of patients such as granularity on screening or [doc] attitude and, importantly, whether or not this may be competing for patients with other trials in the same leukemia silos?

Yes. Let me make a comment, and then I'll turn it over to Helen for some more detail. I will say we're getting enthusiastic responses from the sites. We have sites open now in the United States and Australia, and we'll be shortly opening in Europe. So we're enrolling widely and well, and the study has good momentum. But let me turn it to Helen for comments on -- more granularity around the reaction from some of the investigators.

Yes. So we have had -- as we announced, we had our first patient enrolled in November. We have sites coming online at a good pace in the U.S. and outside the U.S., as Rachel said. And multiple sites are excited about the trial. We've had good momentum with investigators and good momentum with startup with sites. So we're very pleased with that momentum so far. And we've not had much feedback in terms of competing trials for patients. We think that this is a good space. In the relapsed/refractory setting, there is not very much available for patients or available to investigators, and pairing uproleselan with the standard of care is a very attractive option in this clinical trial setting. So we are very optimistic with the feedback we've had so far.

And second, the early pipeline. So thank you for the overview, Rachel. The data at ASH about the antithrombin effect was interesting, and I remember the data from -- I think it was ASCO, where you showed white cell mobilization. How are you thinking about prioritizing the early programs at this point? Because it seems like you can do a lot. And then second, since some of these agents do share a common target with upro, how do you think about the possibility of just advancing your agents versus expanding the upro program, if that's already clinical?

Yes. Well, so I think that you raise a number of important points and actually highlight some of the great opportunities that we think we have going forward. 1687 is a compound that you reference, which is the highly potent E-selectin antagonistic. And as far as the follow-on pipeline is concerned, that would be our next priority of among the compounds that are still preclinical. And I would say that, that first of all, offers a chance for us to take the indications in which we develop upro into a self-administered setting potentially. For example, we know that some of the -- we were currently dosing uproleselan intravenously for patients who are hospitalized while they received their chemotherapy. But you could envision over time wanting to be able to move an AML therapy into the outpatient setting, and 1687 gives us the potential to do that because we believe it will be subcutaneously available. It also, as you indicate, gives us a potential to move into some other indications. I would say our initial focus is going to be to look for other areas within the hematology/oncology space that would allow us to build on the expertise and the relationships that we've built in that area, also focusing, as we have in the past, on areas where we feel that the use of the drug could be potentially transformative and could also lead to streamlined development as well as potentially targeted commercial opportunities. So that's the reference to the 1687. We also have, as you indicated -- you briefly alluded to the fact that there were other molecules and also the Galectin program, which is also preclinical. We introduced one of those molecules, the E-selectin/Galectin combination molecule at ASH. That has a broad potential range of indications, and there are some very exciting indications for the Galectin-3 antagonist alone. So we'll be saying more about what we intend to do with those as we continue to develop the preclinical story. But I think at a high level, what I'd say is you'll see focused clinical programs that build on the expertise that we have but then continue to build out the pipeline based on what really is a unique, very differentiated specialized chemistry platform that we have here at the company.

And I look forward to the rivipansel data.

Thanks, so do we.

Our next question comes from the line of Stephen Willey of Stifel.

So maybe just a couple of sickle cell questions. Just curious as to how you see the potential approval of crizanlizumab perhaps impacting the addressable market opportunity. And I guess second to that, if a patient was taking that drug prophylactically and had a breakthrough, would there be hesitancy at all within the acute care setting to try to address the VOC with an asset that has a somewhat similar mechanism of action?

Yes. So let me take that second question first. We actually think that there would not be hesitancy to use it and no reason not to use it. As you remember -- you may remember, crizanlizumab targets P-selectin, whereas rivipansel is a pan-selectin antagonist with specifically greater activity against E-selectin. And there's a lot of data in the literature that actually speaks to the dominance of E-selectin in the context of a vaso-occlusive crisis. So we think that as a breakthrough therapy -- or as a breakthrough crisis would occur in the patient on crizanlizumab that there would be every reason actually to give rivipansel to that patient in the acute care setting. As far as the addressable market is concerned, I do believe that with all the drugs that are in development now, there will be a number of different therapies potentially available for treatment of sickle cell disease which is good news for patients, but I think these are going to be complementary. You may note that the data from crizanlizumab is very similar to the data that was generated a number of years ago with hydroxyurea, and hydroxyurea has been on the market for about 15 years. It's had an excellent clinical trial output showing that it also significantly reduced the hospitalization for crisis but had very little impact -- has had very little impact over the years on the actual hospitalizations for crisis. So I think fundamentally, although treatment of the disease will improve, I don't think vaso-occlusive crisis is going away. And I'll remind you that rivipansel is the only drug in late-stage development for treatment of crisis. So we think that where there currently is a lot of competition right now in the prophylaxis setting, crizanlizumab, the Global Blood product, hydroxyurea, et cetera, there is no other late-stage development -- no other drug in late-stage development currently for the treatment of crisis. So we think that rivipansel can really own that portion of the market.

Got it. And then maybe just a clarification question. So the dual-functional antagonist, did you say that goes into the clinic later this year?

No, the dual-function antagonist, which is preclinical -- I'm sorry, we have to 2 dual-function antagonists. Let me clarify. There is 1359, which has already been in the clinic, that's completed a Phase I trial and that's the drug we intend to take into a solid tumor trial later this year. There is a second dual-function antagonist which targets E-selectin and the Galectin, which is still at the preclinical stage. But 1359 is already in the clinic, and we intend to continue with the clinical development of that program with the initiation of a solid tumor trial later this year.

Understood. And then just lastly, I know that there was some prior mention of potentially seeing some myeloma data this year. I guess is that still part of the plan? And is the objective again really just to show changes in M protein?

So we have de-prioritized the myeloma program largely because of the changes in the myeloma landscape, particularly with the approval of daratumumab and the way that, that treatment landscape has continued to develop with more options for patients. So we actually have decided to discontinue enrollment in the myeloma trial. We'll continue to gather data on those patients, and we'll see if there's anything that we want to report out about that. But we've decided that we feel there are greater opportunities for uproleselan in AML and potentially in other areas, which we're continuing to explore. But we don't think that -- we think that, given the changing treatment landscape in the myeloma field, we don't see as good an opportunity for uproleselan there as we think we could develop in other areas.

Our next question comes from the line of Peter Lawson of SunTrust Robinson.

Rachel, just following up on the 1359 moving into solid tumors, which tumors are you thinking?

Yes. So we haven't announced specifically what we'll be doing in that trial. We do expect to save that later this year. What I can say though is that we've decided to move into a solid tumor setting in which the tumor has metastasized to the bone. And that's because the preclinical data that we've generated with that molecule demonstrates particular effect in that setting where we've shown that both CXCR4 and E-selectin are involved in both trafficking and maintenance of metastatic sites within the bone. So what we've designed is a study that's going to be looking at both PK in the cancer patients as well as some biomarkers that are going to allow us to begin to explore the potential use of 1359 in the setting of solid tumor metastasized to bone. So we'll be saying a bit more about that later in the year, but that's the general contours of what we expect to do with that trial.

I see. And then just as we think about follow-on molecules, rivipansel, is that completely under the control of Pfizer to be thinking about follow-on molecules there and whether you need to move beyond IV and into subacute? And kind of what else should we be expecting around that?

Yes. So the license with Pfizer is for rivipansel and for drugs which are very like rivipansel, so essentially rivipansel and its family of molecules. We are not continuing work with other rivipansel-like molecules here at GlycoMimetics. However, Pfizer could take rivipansel into other indications if they would choose to do that. Here at GlycoMimetics what we're doing is we are developing our own suite of molecules which are more focused and more potent than rivipansel. They're more -- they're newer molecules and have the benefit of what we learned through the early days of the discovery and development of rivipansel. But they are being taken forward in different indications from sickle cell here at GlycoMimetics. So we're not specifically working on follow-ons to rivipansel here.

Perfect. And then just as we think about the number of trials that are enrolling to upro, are there any that are enrolling better or worse than expected? Just anything you can talk around the metering of patients.

And I'll turn that over to Helen.

I think the question is about sites enrolling with uproleselan in Phase III, and I think at this point, our comment is simply that enrollment has started, enrollment is proceeding well, demonstrating good early momentum. And we have -- also the NCI program is under way. NCI has listed their trial with uproleselan also on clinicaltrials.gov. And so we're looking forward to seeing that trial and progress with that trial over the course of the coming time.

(Operator Instructions) Our next question comes from the line of Biren Amin of Jefferies.

So Rachel, just a couple of questions on rivipansel Phase III design as it relates to the Phase II data that you guys generated. So on the Phase III, I think you're enrolling pediatric patients along with adults. And given that pediatric patients were not enrolled in the Phase II, how do you think it would impact the Phase III? And then also I think the adult patients in the Phase III are receiving a fixed dose which is equivalent to a lower weight base that was used in the Phase II. So a question on what led to the choice of that fixed dose in the adults in the Phase III and how you think that would impact it. And then lastly, I guess what are your thoughts on site-to-site variability and how that would impact Phase III data?

So I think I'll turn those questions over to Helen as she can answer those in a bit more detail.

Yes. Sure. So with regards to pediatric patients, you're correct. This Pfizer trial is enrolling patients down to age 6. In our Phase II trial, we enrolled patients down to age 12, the adolescent and adult population. And Pfizer has included that adolescent and adult population and also I think quite appropriately extended the trial down to the younger group. As you know, sickle cell disease vaso-occlusive crisis occurs across the age ranges of pediatrics and adults. So that seems to be very appropriate for the trial and will allow for a data set that informs the whole population, and so we think that's quite appropriate. In terms of the dosing, there's the fixed dose. The transition from weight-based dosing in the Phase II to a fixed dose in the Phase III is a standard transition. And the adult's dose is based on the exposure levels demonstrated in the Phase II. The -- those exposure levels are looking at exposure on a population PK-based analysis, and so the fixed dose is simply selected to establish the exposure on a fixed-dose level for the adult population. We have taken this approach also with uproleselan, where in our Phase I/II, we had weight-based dosing, and in the Phase III, we've been able to select a fixed dose built on population PK data. So that's a pretty standard approach, and I think we're quite comfortable with the way Pfizer has approached that. And then your third question, I think, was on the site-to-site variability. It is expected that there is variability at a patient level as well as at a site level in any clinical trial, and that's the reason for expanding the number of sites and number of patients in a Phase III program. So that's fairly standard. Pfizer has a large trial with a good distribution of sites that represents the standard of care. They're also very similar to the nature of sites that were included in the Phase II, and so we expect that the standard of care or treatment as well as the outcomes that we'll be seeing should be representative certainly of what we saw in the Phase II as well. It's also a randomized trial which allows you to control for any potential sources of variability. The Pfizer trial is also sized substantially larger than our Phase II. And as you remember, there were some outcomes in our Phase II trial that either achieved statistical significance or trended towards significance even in that small trial. So we think that the Pfizer trial is well designed and well sized to address any variability that might be seen.

Okay. And then I just have one follow-up on upro. Given the Phase II data at ASH, it seems to suggest better outcomes in patients that have favorable intermediate risk compared to adverse risk? And this, I think, is the trend that you saw on both the refractory trial and the newly diagnosed trial. So my question is would you attempt to more heavily recruit favorable and intermediate-risk patients in the Phase III refractory study to have better odds of success.

So I'll have -- let Helen take that one also.

Yes. Actually, we were very pleased with the data that we saw in adverse outcomes in both the relapsed/refractory group in our trial and in the newly diagnosed group. There were substantial levels of patients with adverse cytogenetics enrolled as well as high-risk disease. And they did quite well, especially compared to what you'd expect for those populations. Those populations have a poor remission rate and poor survival. We had patients in those groups -- in that adverse risk group achieve remission and have long survival outcomes with reduction in -- sorry, with negativity in terms of measurable residual disease. And so we believe that, that has demonstrated a deep, durable remission even in patients with adverse risk at rates higher than we would expect from the historical controls. We also know from the work that Pam Becker has done and that John Magnani has done that the adverse risk in those patients who are most likely to relapse early and have refractory disease have a higher proportion of the E-selectin ligand expressed on those leukemic blasts, illustrating that the cells that are most likely to be the cause of relapse or the cause of resistant disease are, in fact, the cells that we think uproleselan is best designed to target. And so our data in the adverse population was very much in line with what we expected to see and hoped to see in terms of targeting those patients with the highest risk and also the highest proportion of the E-selectin ligand on their blast and seeing negativity in terms of measurable residual disease and durable responses.

And I'm showing no further questions at this time. I now would like to turn the call over to Ms. Rachel King for closing remarks.

Great. Thank you, operator. And thank you, everyone, for your questions and for taking the time to join the call. In 2018, GlycoMimetics delivered achievements on all fronts, in clinical development and preclinical research discovery and in finance.

We've put into place a comprehensive Phase III clinical program for uproleselan that, if successful, could position this investigational drug as a foundational therapy across the spectrum of AML. This is an accomplishment that reflects the enthusiasm worldwide of clinicians who've seen our data and its impact to date on patient outcomes as presented at top oncology congresses.

In discovery, preclinical research, our specialized chemistry expertise produced new potential drug candidates to expand our pipeline opportunities into indications that go beyond sickle cell disease and hematologic cancers.

Looking forward to 2019, we're in a strong financial position to pursue the clinical and preclinical opportunities ahead. Importantly, we look to the rivipansel top line readout expected late in the second quarter that could represent the first commercial success of our pipeline and a key financial resource going forward. Thank you very much.

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