Crescent Biopharma, Inc. (CBIO) Q1 2017 Earnings Report, Transcript and Summary

Good morning. And thank you all for joining GlycoMimetics Corporate Update Conference Call. At this time, all participants are in a listen- only mode. Following management's remarks, we'll hold a brief question-and-answer session. And at that time the lines will be opened for you. [Operator Instructions] I'd now like to turn the call over to Ms. Shari Annes of the Investor Relations group at GlycoMimetics. Please go ahead.

Good morning. And welcome to GlycoMimetics' first corporate conference call. Today's call will focus on the just published data contained in the abstract accepted for presentation to both the upcoming ASCO and EHA meetings in June. As you know, we issued our first quarter financial results press release on May 8. Should you have some questions about that topic, we'll be happy to respond in the Q&A session. Copies of our press releases are available in the news section of the company's website at www.glycomimetics.com. Today's call is being recorded and will be available in the Investor Relations section of the company website for 30 days. Joining me on the call today from GlycoMimetics is Rachel King, Chief Executive Officer; Brian Hahn, Chief Financial Officer and Helen Thackray, Senior VP and Chief Medical Officer. Before we start, 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 timing of clinical results and presentation of data from our GMI-1271 clinical development program, as well as the development plans for rivipansel, our product candidate license to our collaborator Pfizer. Such statement represents management's judgment and intention as of today and involves assumptions, risks and uncertainty. GlycoMimetics undertakes no obligation to update or revise any forward looking statement. Please refer to GlycoMimetics' filings with the SEC which are available from the SEC or on the GlycoMimetics website for information concerning the risks factors that could affect the company. I'll now turn the call over to Rachel King, our CEO who will provide an overview of the highlights and discuss the GMI-1271 clinical program. Following Rachel, Dr. Helen Thackray, our CMO will discuss in greater detail the data contained in the GMI-1271 abstract. After some additional remarks from Rachel, we'll then ask the operator to open up the call for your questions. Rachel?

Thank you, Shari. Good morning and welcome to our corporate update call. And thank you all for joining us today. Yesterday, we were very please to announce that FDA has granted Breakthrough Therapy designation to GMI-1271 for the treatment of adult with relapsed/refractory AML. In addition, with yesterday's online publication of abstract by ASCO and this morning's publication of abstract by EHA, the European Hematology Association, I'm delighted to be in a position today to provide you with clinical data update on our GMI-1271 program and offer our perspective on the data. Importantly, my goal today is to share our growing confidence to what we believe could very well be a novel and distinctly differentiated therapeutic approach to AML. To step back just a bit and there is perhaps many of you know GMI-1271 is a potent E-selectin antagonist. It's currently being evaluated in the Phase 2 clinical trial in AML in combination with standard of care chemotherapy. The Phase 2 trial is comprised of two arms. One, treating newly diagnosed AML patients 60 years and older and one treating patients with relapsed/refractory disease. Both arms are evaluating treatment with GMI-1271 and chemotherapy. The enrollment of the cohort of newly diagnosed patients has been completed and we are on track to complete enrollment of the other cohort of patients with relapsed/refractory AML by mid-year. In total and including AML patients enrolled in the Phase 1 dose escalation portion, we expect to evaluate approximately 90 patients consisting of approximately 25 with newly diagnosed disease and approximately 65 with relapsed/ refractory disease. This is a significant sample size and enrollment into this Phase 2 study been brisk. We think the pace of enrollment is indicative of the strong interest that our clinical investigators have for this novel agent. We began reporting the results of the study last year at the EHA meeting and we updated the data in December at ASH just before the year end. GMI-1271 has been consistently well tolerated in the trial with no obvious incremental toxicity observed when added to chemotherapy. Patients receiving the combination of GMI-1271 and chemotherapy treatment in the trial have also experienced higher than expected remission rates and lower than expected 30 and 60 days morality rates. Today's disclosures include new data from 47 relapsed/ refractory patients and 17 newly diagnosed patients. I am delighted to tell you that the updated data in the study gives us growing confidence that GMI-1271 could play an important role in addressing the unmet needs of AML. We based this on three key findings that are specified in the abstract and that would be elaborated in greater detail at the conferences. The first finding is that we continue to see a higher than expected remission rate when GMI-1271 is added to chemotherapy compared to historical controls. The second finding is an exciting and new observation related to one of the biomarkers we are following. We mentioned in the abstracts related to the cohort of patients with relapsed/refractory disease that they find level of E-selectin ligand were predictive of clinical response and tied to greater likelihood of achieving remission of disease following treatment with GMI-1271 and chemotherapy. This is particularly meaningful given the fact that many publications have documented that patients with a variety of cancers expressing high level of E-selectin ligand on their tumors have particularly poor outcome and tumors that are resistant to chemotherapy. Our own AML preclinical data demonstrates that they would be more likely to have worse outcome in absence of treatment with GMI-1271. I'd like to repeat this to be clear. Among relapsed/refractory patients treated in our study, patients with higher level of E-selectin ligand on their leukemia cells are more likely to experience remission of their disease when GMI-1271 was added to conventional chemotherapy. We see this even now without GMI-1271 treatment based on our preclinical data, they would have been expected to have worse outcome. This new observation provides strong evidence of clinical proof of concept that supports the mechanism of action of GMI-1271. This data is the result of a prespecified analysis of ligand on the leukemia cells and assessment of the associated responses. It's our plan to continue to follow this important new observation as our data mature to confirm and expand the potential correlation between this biomarker and clinical outcome. This observation builds directly on what we and others have reported in the preclinical and clinical settings about the key role of E-selectin in many forms of cancers including AML. Importantly, this provides what we believe is the first direct clinical evidence of the potential benefit of targeting E-selectin in this difficult to treat population of AML patients. Lastly and consistent with our differentiated mechanism of action, we are continuing to observe lower than expected induction related mortality. While we won't elaborate it on today, we'll be presenting data at ASCO and EHA on specific protective effects that we are observing, also consistent with our preclinical data which provides further support for GMI-1271's biologic activity. The consistency of our data readout is good news in itself, AML has long been a tough indication for the developers of new therapeutics and we now have growing confidence that our investigational drug GMI-1271 may play a role in addressing key unmet needs of this deadly cancer. In addition, the breakthrough therapy designation received yesterday provides critical support and gives us the opportunity to work closely with the FDA to expedite our development plan. I'll now turn the call over to Helen. Helen?

Thank you, Rachel. Two GlycoMimetics abstracts have been selected for presentation at ASCO and two have been accepted for presentation at EHA. At both of the meetings in June we will provide updated data. To be clear, the results we are discussing this morning are the results of a late January data cut and are what is reported in the abstracts. The first abstract selected for poster with discussion at ASCO, updates data we provided at ASH for the relapsed/refractory arm of the study. The second selected for poster presentation reports on results seen in a newly diagnosed population of elderly patients. To step back a bit, GMI-1271 is a novel antagonist E-selectin that down regulate cell survival pathway and in animal model disrupts blast appearance in the bone marrow and enhance its survival when added to chemotherapy. In addition, in preclinical studies, reductions in chemotherapy induced mucositis were also observed following the administration of GMI-1271. Let's first turn to the relapsed/refractory findings that will be part of the poster with discussion at ASCO on Monday June 5. This is abstract 2520.We assessed GMI-1271 for salvage chemotherapy with mitoxantrone, etoposide and cytarabine or MEC for the treatment of patients studied. In the Phase 1 portion of the study, we dose escalated GMI-1271 across the pharmacologically active dose range from 5-20 mg/ kg combined with MEC induction. Treatment was well tolerated at all dose levels. In the Phase 2 portion, we've added the option for responders to receive consolidation with GMI-1271 and MEC. Safety, tolerability and anti-leukemia activity were evaluated and a prespecified analysis also included assessment of expression at the E-selectin ligand biomarker. The recommended Phase 2 dose of GMI-1271 used in the Phase 2 portion of the study was 10 mg/kg. As also shown in our prior published research in ASH in 2016, the addition of GMI-1271 to MEC chemotherapy has been tolerated with a high overall response rate, low induction mortality and what we believe our promising initial survival outcomes in patients with relapsed/refractory AML. Furthermore, as Rachel indicated in patients evaluated to date, baseline expression of the E-selectin ligand biomarker was predictive of response. Highlights of the details reported in the published abstract today are as follows. 47 patients were enrolled to date; 30 and 60-day mortality were 0% and 7%, respectively. The Overall Response Rate was 21 out of 42 subjects evaluable for 50%.Median Overall Survival in the Phase 1 portion of the study was 7.6 months. The median E-selectin ligand binding at baseline was 35% of blasts with a range from 1% to 75% and, importantly higher in those achieving remission. Historical controls in AML are robust given the treatment regimens and outcomes have not changed in decade. We feel their appropriate comparisons with this study and that we can confirm enrollment of similar patient populations to those treated in recently published studies. Based on this historical control in particular by Greenberg et al and JCO 2004 and by Feldman et al and JCO 2005, we believe the overall response rate 30 and 60 days survival and overall median survival as reported in our Phase 1 population all show improvements over what would be expected with treatment by MEC chemotherapy alone. As noted earlier, we report for the first time in the ASCO abstract that overall survival of patients treated in the Phase 1 portion of our study was 7.6 months. This compares to 5.4 months and 5.2 months in the Greenberg and Feldman papers respectively. Based on this, we are very encouraged by the growing data set. I'll take a minute to discuss the new finding that we are seeing in association between likelihood of remission and baseline levels of the E-selectin ligand biomarker on the leukemia cells. If you recall, we also showed last year in preclinical studies presented at ASH that AML blast with higher level of E-selectin ligand were chemo resistant and its sensitivity to ceritinib was restored with the addition of GMI-1271. The preclinical data combined with our emerging clinical observation support I belief that this biomarker, the E-selectin ligand has clinical relevance. And further at interruption of E-selectin mediated interactions may improve outcome in AML. We've also seen this in other cancers including in multiple myeloma. Data from our preclinical studies to GMI-1271 and that indication were published online by Journal Leukemia and were the subject of our May 2 press release. In those studies, myeloma cells with higher levels of E-selectin ligand were associated with more aggressive chemo resistant disease. With this chemo resistant being broken after administration of GMI-1271. Our preclinical data also supports the encouraging safety profile of GMI-1271 in combination with chemotherapy. And we look forward to reporting updated clinical safety data at ASCO and EHA as well. As a clinician, I find this translation of preclinical data to clinical outcomes truly exciting. The GlycoMimetics team is working hard to determine an appropriate and efficient regulatory path and clinical trial design to move forward. I can tell you that our investigators are enthusiastic as well. And the rate at which they enrolled this study when there are multiple clinical trials available to these investigators and their patients is a testimony to their dedication and support for this potential therapy. We are committed to share our plans once finalized for moving forward with this novel therapy, taking into account those consistently encouraging data and this key new biomarker finding. When we present at ASCO and EHA, we'll include what is known so far about this biomarker and the data from the updated data cut. Now let's turn to the second ASCO abstract no 2560. Reporting data on GMI-1271 in a newly diagnosed patient population of individual 60 years and older with AML. This poster will also be shown on Monday June 5 in Chicago. And there will be poster presentation of this data at EHA as well. As I am sure you know, the outcomes for elderly patients with AML remain poor and tolerability of treatment is a key concern. Therefore, new more effective, less toxic treatment regimen is urgently needed. GMI-1271 at the Phase 2 dose of 10 mg/kg was given 24 hours prior during and 48 hours post induction with infusion ceritinib and idarubicin also called 7 plus 3, safety, tolerability and anti leukemia activity were assessed. Two cycles of induction were allowed and responders could receive consolidation with GMI-1271 plus intermediate dose of ceritinib. Here in the published abstract we report on 17 of 24 enrolled subjects. At ASCO and EHA we'll also update this data. But today we are sharing the following highlights from the abstract. The remission rate CR/CRi was 12 out of 17 subjects or 71%. CR/CRi rate was 75% for patients with de novo disease and 67% for patients with secondary AML. Again, I believe the comparison to historical control is also relevant in this frontline setting and infusion ceritinib and anti cycling has been the mainstay of intensive induction chemotherapy for the past 30 years and the benchmark efficacy data is well established with this regimen. Our data in this newly diagnosed population stacks up very well against the historical remission rate of 50% to 55%. In this population as well we are encouraged by the safety profile GMI-1271 in combination with chemotherapy. And we look forward to reporting this data at ASCO and EHA. To summarize then the key message is that based on new data ASCO and EHA have just released, we are confident first that response rate, survival outcome and short-term mortality in the study so far compares favorably with similarly matched historical control, supporting a potential role for GMI-1271 in AML. Second, we believe this data discussed today provides direct clinical evidence of the potential benefit of targeting E-selectin in this highly differentiated therapy for AML. Third, based on our preclinical data, patients who express higher level of the E-selectin ligand on the leukemia cells would be expected to have worse clinical outcome. Yet in this study, relapsed/refractory patients who express higher levels of the E-selectin ligand on their leukemia cells had higher rates of remission with the addition of GMI-1271 to standard chemotherapy. As Rachel also indicated, we are especially pleased that yesterday the FDA granted breakthrough therapy designation to GMI-1271 for treatment of adult with relapsed/refractory AML. We look forward to working closely with the agency as we bring this therapy as quickly as possible to patients who may benefit from it.

Thank you, Helen. To close, I'd like to reiterate that our plan with GMI-1271 going forward is to continue to report data as it matures at key oncology conferences, the next of which will be ASCO and EHA in June. We anticipate that this would then be followed by a more complete report at ASH in December based of course on our submission and their acceptance of an abstract. Our clinical program with GMI-1271 also includes a GlycoMimetics sponsored Phase 1 study in patients with multiple myeloma disease has become resistant to bortezomib or carfilzomib. In this study, GMI-1271 is added to their chemotherapy treatment regimen to evaluate whether sensitivity to the produced inhibitors can be restored. This is a multi center open label dose escalation trial being conducted in Europe. It's important to note that the finding of the importance of E-selectin ligand is not limited to AML and myeloma. I referred earlier to a large body of publication in addition to our own work that speaks to the relevance of E-selectin ligand poor prognosis. We prepared to background or summarizing this data which you can find on our website and which hope will be helpful to you as you think about how to consider the observations about the biomarker published today in the abstract. On another note, we can report that the Phase 3 program to evaluate rivipansel for vaso-occlusive crisis of sickle cell disease. According to our parter Pfizer remains on track and is a cool target for completion in the second half of 2018. I remind you that our partner Pfizer is managing that trial and that under special protocol assessment agreement with the FDA, the plan is to evaluate data from 350 patients. Given our own Phase 2 data with rivipansel that was selected for best of ASH and the recent positive Phase 2 results with the selectin P-select and antibody that was presented at ASH last year, we are increasingly confident in our approach to treat vaso-occlusive crisis or VOC. Through our own work and others, selectin have been shown to play an important role in the path of physiology at VOC. Based on the inherent challenges of compliance with prophylactic regimens, we believe our pan selectin approach in the acute setting is uniquely and well positioned to address key unmet needs in this underserved patient population. To conclude, going forward we will be developing a clinical and regulatory strategy taking into account these recent observations with GMI-1271 and taking advantage of the opportunity provided by the breakthrough therapy designation granted yesterday. We'll do this while continuing to generate longer-term follow up data on patients in our Phase 2 study including looking at effects of multiple cycles of therapy. As we do this, we also move towards the read out from the rivipansel Phase 3 study. I'll turn the call over now to the operator to address your questions. Operator?

[Operator Instructions] Our first question comes from Yatin Suneja with SunTrust. Your line is open.

Good morning, guys. Congrats on the data and breakthrough designation, it's really great. Just a couple questions I have starting with biomarker data. I think the first time you are talking about this data especially in patient. So is there any threshold at which you are seeing maybe better response 1271? I mean I know the median binding was about 35% but the range seems to be up to 75%. So is there any correlation that you are seeing or is there a particular threshold beyond which you are seeing higher responses?

We haven't announced anything about the threshold. The announcement I have to -- the information we disclosed today I think has to be limited to what was disclosed in the abstract in which we indicated that it was predictive of response. And the higher levels of the biomarker were associated with more likely remission. We will be disclosing additional data around that at ASCO and at EHA.

Okay. And then in frontline patient, are there any differences in terms of level for the frontline AML patient relative to relapsed/refractory?

Again, I am afraid I have to limit myself to the data that's in the abstract but we will be sharing more when we know about that at ASCO and at the EHA as well.

Okay. And then in terms of the future development plans, I mean since you now have a breakthrough designation, are you planning to prioritize one indication versus the other? And at what point you will be meeting with the FDA? And what is your expectation for -- like how do you think the registration programs going to look like?

Well, as I indicated we received the breakthrough therapy designation just yesterday which we are of course thrilled about and so we haven't yet had conversation with the FDA in that context. We've been doing a lot of thinking about plans for the program and so that puts us a in a good position to have those conversations with the agency which we anticipate doing later this year. And once we have a clear path described and outlined together with the agency we will be sharing them.

Okay. Maybe just one more then again going back on the biomarker, I mean how are you doing that? Are you using flow cytometry and then let's say if you do a future trial or future trials would you prescreen patients for high E-selectin ligand bindings?

The assay that's currently being run in the Phase 2 study is being done by flow. And we are looking at flow and other ways that the assay could be done going forward. As far as whether we would use that or how would you use that in future studies, again I am afraid I am going to have to defer that comment. Importantly though the breakthrough therapy designation as we announced, it is not limited to patients with high levels of expression of the biomarker. The breakthrough therapy designation is for patients with adult or adult with relapsed/refractory disease. So we are in the process of evaluating of how we can incorporate the biomarker into the development plans. Again, we'll share that information when we know more.

Thank you. Our next question comes from Stephen Willey with Stifel. Your line is open.

Yes, good morning. Congratulation on the updates and on the breakthrough. I know so in the abstract last night you showed I guess for the first time leukemia free survival and overall survival in the phase of one portion of the relapsed/refractory study. Can you just remind us whether or not 1271 was allowed during consolidation in the Phase 1 portion? Because I know that the trial protocol was amended at some point to allow for 1271 beyond induction. I am just trying to think about those data points in the context of dosing.

Yes. That's a very important point actually and a distinction between the Phase 1 and Phase 2 portion of the study. So let me turn that to Helen to address that more specifically.

Thank you. So in the Phase 1 portion of the study we administered GMI-1271 with induction chemotherapy, it was not available with consolidation for responders. In the Phase 2 portion of the study we had added then the opportunity for responders to receive GMI-1271 with consolidation MEC chemotherapy in relapsed/refractory and with consolidation intermediate dose Ara -C in the newly diagnosed older population. So we treated for one cycle of chemotherapy with GMI-1271 in the Phase 1 and those of the data that are reported. And we anticipate reporting at a later time the data from Phase 2 when treatment with multiple cycles with an option.

Okay. That's helpful. Thank you. And then I guess with the discussion around E-selectin as a biomarker. It's obviously some telling to be identified predictive of response in this disease but I guess just given the mitigation of the chemo induced toxicity, do you think that there is an even need to pre-select patients on the basis of E-selectin ligand expression specifically in the relapsed/refractory setting?

I think that raises a very interesting point and I am glad that you mentioned it because while we do see this relationship with respect to remission, we have not said anything about whether that -- in fact one wouldn't expect that it would be the case that patients will have to have higher level of E-selectin ligand on their tumors in order to see a potentially beneficial effect during the induction chemotherapy. I am just saying that based on our preclinical data. In our preclinical data, we showed reductions in chemotherapy induced mucositis which were quite pronounced in the animal model. We haven't disclosed data yet on that in the abstract but we will report on it when we know it at ASCO and EHA. But I think you are correct that one not might necessarily need to select for patients to see that benefit in the induction phase. So that's a very and certainly an interesting observation we've seen pre-clinically and we are excited to follow that in the clinical setting as well.

Okay. And maybe just one more if I may. So I guess as you think about the Phase 3 trial design or some advanced trial design here in relapsed/refractory setting, would you think that you would have to specify NEC as a control arm or would you expect that to be kind of more of physicians' choice type of decision? And then maybe if you Rachel whether expect to just broader strategic question is the Phase 3 something that you would like to take on by yourselves or would you prefer to maybe pursue some kind of cost and risk sharing arrangement? Thanks.

Sure. Let me turn it first to Helen to address the control arm in the Phase 3 in the current topic.

So we know from this trial the effects that we are seeing with MEC chemotherapy; we know also from our preclinical data that survival benefit over chemotherapy is seen with multiple different times of chemotherapy. And so we would want to discuss with the agency about the program going forward whether it's appropriate to treat as we have with MEC chemotherapy or perhaps broaden to other chemotherapy options available to the physicians. But the preclinical data would be supportive of a broader approach.

And then to your question about our strategic options and plus the partnering, I think it's premature to make any comments about any specific partnering plans but I'd say that it would certainly be our goal to preserve significant value within the company if we do engage in any partnership around this program.

Thank you. Our next question comes from John Newman with Canaccord. Your line is open.

Hi, guys, good morning. Congrats on breakthrough and the interesting data here. Thank you for giving us an update. I have two questions. The first one is just wondering if you could discuss at all the percentage of patients in the relapsed/refractory portion of the study that we are able to go on to receive a transplant given your very high rates of early response? And the second question I had was also on E-selectin and obviously understand that you can't talk about things that haven't yet been disclosed but can you say with E-selectin whether there was a trend towards higher response with higher E-selectin levels or was there a level above which the majority patients had a response? Thank you.

So let me answer the second question first and then I'll turn it over to Helen for the question about transplant. As far as the specific data on E-selectin, again I am afraid I am going to have to defer that to ASCO. We'll be sharing everything that we know as of that data cut in the context of ASCO and EHA. So I encourage you to tune back and then we'll be able to say more that way. And let me turn it to Helen for the question about transplant.

So in the context of relapsed/refractory group, one of the things that we are interested and evaluating is the durability of remission and the ability to sustain remission therefore long enough to get through the complicated process of preparing for an identifying a transplant. We have seen some patients go on to the transplant, we reported that in the Phase 1 portion of the report at ASH and we will update that with the further information available at the ASCO and EHA presentation.

Our next question comes from Ritu Baral with Cowen and Company. Your line is open.

Good morning, guys. Thanks for taking the question. I wanted to ask just few more specific from the two subsist test that you did. That you did disclose in the relapsed/refractory population. Given E-selectin's role in immune response, was there anything unusual about these two subsist tests out of the ordinary from a normal chemo toxicity?

I'll let Helen answer that too.

So we did report in the newly diagnosed population and older population, we had two test of subsist within the first 60 days on study. It is actually unfortunately a population that has a very high rate of death subsists and so two deaths in that group are not at all unusual. And we've had no indication in the preclinical data or the clinical trial data reported publicly so far that there will be any increased risk of infection with this mechanism. We'll certainly discuss further with the other safety details that are reported at ASCO and EHA.

Got it. And then turning to Europe, now that you have breakthrough therapy and all the allowances with FDA as part of that program. What is the European strategy going forward with EMA? Are you going to apply for a prime designation? Is that a possibility and how do you look at that regulatory strategy as well as the business strategy over there? Is that a territory that you'd be interested in keeping or potentially a separate partnership?

We certainly are exploring the options in Europe as well as possible with our designation that could be helpful there from -- so answer that from a strategic standpoint. As far as clinical issues, Helen could you comment on our path for year.

So as the program looks forward we would expect to engage with regulatory agencies. We will as you know engage with the FDA with the breakthrough therapy designation opportunity. We would also expect to engage with the European agency through scientific advice process and seek their guidance on the appropriate path to take in Europe from a regulatory standpoint.

Got it. And then last question just about your multiple myeloma trial. Can you talk about how that's enrolling and potential timeline around that -- those dataset?

We are enrolling in that study now in Europe. We have decided to add additional sites and additional countries. That study was initiated in Ireland. So we are currently in the process of expanding that and adding some larger additional sites. And as we get those other sites online we get a better handle on the accrue on that study and then at that point we will able to give some more tangible guide as to when we expect to get top line readout. The study is continuing to accrue though and we are actively adding sites.

I am showing no further questions at this time. I'd like to turn the conference back over to Rachel King for closing remarks.

Thank you and thanks everyone for your questions and for taking the time to listen to the call. In closing, we believe that 2017 is an important year for the company. Data from the pipeline of investigational new drug products will continue to be submitted to key cancer meetings and we hope that this should -- hope and believe that this should further validate both our pipeline and our platform. So thank you very much for your interest and for your support.

Ladies and gentlemen, thank you for participation in today's conference. This does conclude the program. And you may now disconnect. Everyone have a great day.