Epizyme, Inc.
Q4 2016 Earnings Call Transcript

Published: 9 Mar 2017

[Operator:]

Good morning, and welcome to Epizyme’s Fourth Quarter and Year-end Conference Call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session after the prepared remarks. Please be advised that this call is being recorded at Epizyme’s request. I'd now like to turn the call over to Monique Allaire, with THRUST Investor Relations. You may begin.

[Monique Allaire:]

Thank you, and good morning, everyone. Earlier today we issued a press release outlining our financial results, which is available in the Investor Center of our Web site at epizyme.com. In addition, we will be using slides for today’s call, which can also be found in the investor center of the Web site. Joining me are Rob Bazemore, CEO; Dr. Peter Ho, Chief Medical Officer and Andy Singer, Chief Financial Officer. Additional members of the executive team will be joining us for the Q&A session. During this call, we’ll make forward-looking statements related to Epizyme's future expectations and plans, which are subject to risks and uncertainties. Actual results may differ materially due to various important factors, including those described in the Risk Factor section of Epizyme's Form 10-Q filed in November in 2016. These statements represent our views as of today and should not be relied upon as representing our views as of any date in the future. We undertake no obligation to publicly update our forward-looking statements. I'll now turn the call over to Rob.

[Robert Bazemore:]

Thank you, Monique, and good morning, everyone. At Epizyme, we continue to make tremendous progress towards our vision of rewriting cancer treatment through novel epigenetic medicines. Execution on each of our near-term priority is positioning us well to achieve our long-term strategy for growth and to realize our vision. 2017 is set to be a pivotal year for Epizyme. We’ve a broad clinical development program underway with our lead asset tazemetostat in numerous tumor types as monotherapy and combination therapy and in the relapsed refractory and front-line treatment settings. We plan to report data from our ongoing Phase 2 study in INI1-negative solid tumors at ASCO and engage with regulatory authorities midyear to discuss the path to registration in this program. We believe that this program represents the first potential approval opportunity for tazemetostat in 2018. We also plan to present data from our ongoing Phase 2 NHL study at the international conference on malignant lymphoma in June. This will be followed by regulatory discussions in the second half of the year to talk about our registration strategy in NHL. In both NHL and molecularly defined solid tumors, our regulatory approach is to bring tazemetostat to patients as quickly as possible, while generating the additional data needed to support label expansions over time. We're also advancing multiple additional studies with tazemetostat and we plan to announce our next development candidate from our preclinical pipeline this year that will move into the clinic in 2018. Importantly, we put ourselves financially in a strong position to support these activities with a runway that gets us through the majority of our key 2017 milestone with over a year of cash on hand. Critical to Epizyme's success is the ability to evolve. As a part of one of our most recent evolutions, we announced this morning that Bob Copeland will be retiring from Epizyme. For the last 8 plus years, we've had the incredible benefit of having Dr. Robert Copeland at the helm of our research organization. Bob is a leading figure in the field of enzymology and has helped pave Epizyme's leadership in epigenetic. It is with tremendous gratitude that we announced that Bob will be leaving Epizyme in the second quarter. I'm incredibly proud of Bob's numerous contributions to Epizyme during his tenure which include creating the foundational science on which this Company has been built. We're continuing our natural evolution from a pioneering early science organization to one that is focused on bringing multiple oncology product candidates into and through clinical development at a steady cadence. Bob's scientific accomplishments are further evidenced by his recent appointment as a fellow of the American Association for the Advancement of Science. This is a recognition of his distinguished work to advance the field. We will miss Bob's leadership, but I'm delighted that he will remain a part of Epizyme's future and in advisory role. We wish Bob all the best in this next phase of his career. Epizyme's discovery engine has produced a robust portfolio programs against novel classes of epigenetic targets. We continue to advance a number of small molecule programs under our collaborations with Celgene and GlaxoSmithKline, which includes the novel PRMT5 inhibitor that GSK put into the clinic last year. And we’re developing small molecules against multiple new classes of epigenetic targets that will be wholly-owned programs. For the purpose of today's call, we will focus on the comprehensive development program underway evaluating tazemetostat in molecularly defined solid tumors and in non-Hodgkin lymphoma. Tazemetostat is our first in class EZH2 inhibitor, the most advanced in the industry. It's taken orally, twice-daily and has demonstrated a favorable safety profile in over 400 patients across all of our clinical trials. These are particularly important attribute for its potential use as a monotherapy and a combination agent, and for its long-term use. We're developing tazemetostat as a treatment for multiple types of molecularly defined solid tumors, including tumors characterized by the loss of a protein called INI1. Patients with these tumors such as epithelioid sarcoma and rhabdoid tumors have a poor prognosis. They also live less than one year after relapse. Current estimates suggest that approximately 2,000 people are diagnosed with INI1- negative tumors each year. Today there is no established standard of care for these patients. Due to the lack of treatment options and the severity of these cancers, we believe that this patient population likely represent the fastest path to market for tazemetostat. As such, tazemetostat could be the first treatment specifically approved for patients with INI1-negative tumors, such as epithelioid sarcoma. This is a strategically important program for tazemetostat. We're exploring the full breadth of its potential in these rare tumors in our ongoing global Phase 2 trial. Late last year, we fully enrolled two cohorts of patients, epithelioid sarcoma and synovial sarcoma. During the ASCO annual meeting in June, we plan to provide an update on all arms that have reached their futility assessment by the independent data monitoring committee. Epithelioid sarcoma is a cancer that can be aggressive in the relapsed and refractory setting. This cohort surpass its futility hurdle with encouraging early activity including confirmed objective responses. We've expanded this arm to enroll an additional 30 patients for a total now of 60, so that we can generate more treatment experience. This cohort represents the largest prospective study to date in this deadly cancer. We also surpassed futility in the synovial sarcoma cohort. However, the activity did not meet our threshold to continue studying tazemetostat as a monotherapy. This is consistent with our Phase 1 experience and unlike the other cohorts, synovial sarcoma is an INI1 deficient tumor rather than one characterized by a complete loss of protein. Enrollment is ongoing in this Phase 2 study and in addition to preparing for ASCO we're also preparing for regulatory discussions beginning with the FDA midyear to determine the registration path and INI1-negative tumors. Another component of our solid tumor development program is the investigation of tazemetostat as a treatment for mesothelioma. Following diagnosis less than one in every 10 people with mesothelioma will survive more than five years. Mesothelioma is a very difficult to treat cancer affecting nearly 12,000 people each year in major developed areas. Half of patients diagnosed have tumors characterized by a loss of function of the gene known as BAP1. We are underway with a Phase 2 study to evaluate the efficacy and the safety of tazemetostat in patients with mesothelioma, characterized by BAP1 loss-of-function. We expect to complete enrollment this year to determine the clinical activity and safety. In addition to our solid tumor program, we have a very robust development program for tazemetostat in the treatment of non-Hodgkin lymphoma. About 150,000 people are diagnosed each year with NHL. This is a large and growing patient population. DLBCL, the most common type of NHL, is an aggressive rapidly progressing disease. Roughly half of the patients who initially respond will eventually relapse and maybe refractory to their next treatment. We're recruiting patients into our trial who have already been treated with at least two, but as many as eight prior lines of therapy. Objective responses lead a complete or partial responses, especially those of long duration from a treatment with a low incidence of side effects are clinically meaningful. A higher proportion of patients with follicular lymphoma initially respond to therapy. However, the majority of these patients ultimately relapse. Follicular lymphoma remains incurable. Despite all of our medical advancements, treatment for NHL is not optimal today. Our clinical development program is evaluating the benefits of tazemetostat across both the relapse refractory setting as well as the larger frontline setting. We are setting tazemetostat as a monotherapy and in a variety of combinations, which have become the hallmark of efforts to develop deeper remissions in NHL. Approximately 15% to 20% of patients with NHL have tumors that carry an EZH2 mutation. There are no targeted therapies for these patients. Our initial registration strategy in NHL will likely be in patients with EZH2 activating mutations. And notably last November we received fast-track designation for DLBCL patients with an EZH2 mutation. Let me ask Peter to provide a few additional updates on our NHL program.

[Peter Ho:]

Thanks, Rob. As most of you know, we presented early data from our ongoing Phase 2 study at the ASH Lymphoma Biology meeting last June. This study like that in solid tumors is enrolling patients with various types of NHL both with and without EZH2 mutations. Clinical activity was observed across all study cohorts with a favorable safety profile. With growing experience of EZH2 inhibition in this disease and based on emerging data, we continue to believe that prolonged exposure to tazemetostat has the potential to result in decreased tumor burden over time. Our study design assigns patients to each cohort based on their cell of origin and their EZH2 mutation status. Per protocol, the cell of origin classification is done according to the Hans Algorithm. If you’re looking at our slides, we point you to the chart on the right-hand side. This shows the responses across 47 evaluable patients in four arms of the trial as of the date of cutoff for the ASH Lymphoma presentation in June 2016. Recall that at that time, the follicular lymphoma EZH2 wild-type cohort had not yet surpassed its futility hurdle. As we expected, there were multiple confirmed responses across the four cohorts and a number of patients who are still on study demonstrating stable disease. Because of the known 20% misclassification rate with the Hans test, we're retrospectively assessing patients cell of origin using nanostring, a newer and more accurate test. Using nanostring we learned that several patients with EZH2 mutations that had been previously classified as non-germinal center DLBCL by Hans are actually germinal center DLBCL by nanostring. Given the discrepancy between the two tests, if we focus on just EZH2 mutation status and look at the same 47 evaluable patients, we now see differences in responsiveness between those with EZH2 mutations and those were a wild-type. The data showed a 43% overall response rate in DLBCL patients with EZH2 mutations. Combined with our early results in FL patients with EZH2 mutations, these findings are consistent with our scientific hypothesis that B-cell lymphoma patients with EZH2 mutations may experience greater clinical benefit. Since ASH Lymphoma, we’ve surpassed utility in all five arms of the study and have completed patient enrollment in three of the five arms. Additional sites are coming on board and we have a number of efforts underway to support continued enrichment of patients with EZH2 mutation. Let me pass the call back to Rob to continue.

[Robert Bazemore:]

Thanks, Peter. In June, we intend to provide an update on all study cohorts at the ICML meeting in Lugano, Switzerland. [Technical difficulty] and pending acceptance we plan to present efficacy data by both Hans and nanostring, as well as safety and biomarker data. We're also preparing for regulatory discussions beginning with the FDA in the second half of the year. We expect this dialogue will help us to find the fastest path to registration for tazemetostat in NHL patients. Monotherapy treatment in the relapsed refractory setting is just one of the ways that we are studying tazemetostat and NHL. Its oral administration and its tolerability profile make it an ideal candidate for the frontline treatment setting. In addition, based on the broad impact of its mechanism of action, tazemetostat may be suitable for combination with other anticancer treatments. We have two combination trials with tazemetostat underway. One, takes tazemetostat into the frontline setting in combination with our job, a standard of care in newly diagnosed patients with DLBCL. We are setting the combination at high risk elderly patients, a population that tend not to respond as well as R-CHOP. We have extensive preclinical data showing synergy between tazemetostat and R-CHOP, which we are exploring in this Phase 1b/2 trial. The other study is a combination with Tecentriq, conducted in collaboration with Genentech. Preclinical evidence suggests that EZH2 inhibition may enhance the activity of checkpoint inhibitors. Biomarker data being collected in the study could inform an even broader set of tumors or this combination makes sense. Enrollment is ongoing in both trials. We look forward to establishing the optimal dose of tazemetostat in combination this year and to further enrolling each study to establish the safety and efficacy profile of both combinations. There are a number of additional tazemetostat combinations that we're interested in investigating, supported by compelling biological rationale and preclinical research. We plan to start two new combination studies this year. The setting where we’ve observed the strongest preclinical synergy with tazemetostat is with prednisolone, a standard agent in a variety of NHL treatment regimens. Prednisolone is the P in the CHOP chemotherapy regimen. Based on our preclinical data, we plan to initiate a combination of tazemetostat with prednisolone in relapsed/refractory DLBCL patients. We wanted to evaluate the synergy of these two agents in a clinical setting and more importantly explore the potential of prednisolone to initially slow disease progression, thereby allowing tazemetostat more time to work. This has been initiated as the sixth cohort in our ongoing Phase 2 study. This will allow us to continue to enroll DLBCL patients who are EZH2 wild-type. The second combination study we intend to start is in follicular lymphoma. We are in the process of finalizing the design for this study and we will provide details once completed. Behind our clinical program is a research effort that is building a pipeline of next-generation small molecules against several novel targets and even novel classes of targets. This year we plan to name our next epigenetic development candidate. This is a first in class program addressing a new target and a new indication. We expect to submit an IND and initiate clinical development for this agent in 2018. This is the first of three new product candidates that we plan to advance into the clinic by 2020. As I said at the outset, we plan to conduct all of these activities that I’ve described while still having well over a year's worth of cash after our presentations of Phase 2 data in both solid tumors and NHL. Let me ask Andy now to review our 2016 financial results. Andy?

[Andrew Singer:]

Thanks, Rob. We have the financial strength to deliver on our 2017 goals. We ended 2016 with $242.2 million in cash, cash equivalents and marketable securities and no debt. We expect this capital will be sufficient to fund our operations into at least the third quarter of 2018. This does not take into account any milestones, option payments, or other potential non-dilutive sources of cash, such as from partnering activities that might further extend our runway. Importantly, this capital position allows us to achieve almost all of our key 2017 milestones with over a year of cash on the balance sheet. Our R&D expenses were $91.5 million for the full-year of 2016. As we look ahead to 2017, we expect R&D expenses to continue to increase with our enhanced investment in the tazemetostat clinical program and related activities, as well as advancement of our discovery pipeline. G&A expense was $28.4 million for the full-year of 2016. In 2017, we expect G&A expense to increase as we expand our business development and strategic planning efforts and support pre-commercial activities. All in all, we remain in a solid financial position as we look forward to a milestone rich year. Now I will turn it back to Rob.

[Robert Bazemore:]

Thanks, Andy. 2017 promises to be a transformational year for the Company. We expect to make significant strides on our tazemetostat clinical program this year. We will be presenting data from both our solid tumor and NHL Phase 2 trial and engaging with regulators to define registration path in both. We have already initiated a combination of tazemetostat and prednisolone in DLBCL. We also expect to advance our R-CHOP and Tecentriq combination studies to fully enroll our mesothelioma study and to begin a combination study in follicular lymphoma. In parallel, we're preparing to name the next development candidate from our epigenetic portfolios with an IND and first in human study targeted for next year. 2017 is a big year for the Company, and we look forward to [technical difficulty] these important milestones. Thank you for joining us and we’d be happy to answer any questions.

[Operator:]

Thank you. [Operator Instructions] Our first question comes from the line of Geoffrey Porges from Leerink.

[Geoffrey Porges:]

Thanks very much and Bob Copeland congratulations on [indiscernible] accomplished with the Company and the pioneering work in epigenetics. Wish you all the best. So, a few questions and perhaps directed to Peter. First, on the INI-negative solid tumors, what’s the response rate do you need to see for this cohort of patients to be viable from a regulatory standpoint? And then, I had a question also on the nanostring analysis. Could -- I’m still little confused about the responses that you saw in the non-EZH2, the EZH2 wild-type. Are you suggesting that once you reclassify them that you’re really not seeing the same depth of responses, because it still looks as though you’re still seeing some pretty good responses, i.e., with some CRs in wild-type. I’m just trying to understand what’s going on? Is that -- can you tell us where you’re seeing the signal there? And then lastly, on the combinations, there were lot of other promising new drugs coming into these B-cell malignancies. I’m wondering where you think -- whether you think you might have an opportunity in combination with things like ibrutinib, [indiscernible] molecules so you could get away from chemo, particularly in the elderly patient population and have you looked at CLL. So, sorry for all the questions, but very interesting sort of catalyst coming up. Thanks.

[Peter Ho:]

Okay, Geoff. Well, thanks for the questions and it’s a low [ph] to start off with first, but I will give in my best shot. So with respect to the INI1-negative tumors, these are a set of tumors that really previously have not been studied very well, partly because the identification of INI1 as the molecular signature for many of these tumors, which can arise in all different parts of the body has been a recent phenomenon. And when we look through the literature there aren't many files for these tumors. In fact, for epithelioid sarcoma the -- our current 202 study represents to our best look the largest prospective clinical trial of these patients that has ever been performed. So we look forward to engaging with regulators in a discussion for these tumors, we have described, Rob had that these are tumors that have high unmet need and there are no standard therapy. So I think it's within that context that we would be discussing what would be the appropriate criteria that both we and regulators would feel comfortable moving forward with. But again this is a very vastly different situation than, let's say, melanoma or breast cancer for which there are many available drugs and in fact the decades of experience with drugs that are active. With respect to your second question, the reclassification of the NHL patients. So absolutely we feel that there is activity for the drug in patients who are EZH2 wild-type and we look forward to showing additional data from this trial later this year as Rob had mentioned. Now when we reclassify, the issue is that as you know for the DLBCL GCB cohort for the FL cohorts we divide patients up into groupings of whether their tumors have an EZH2 activating mutation or not. The one group that we do not are the DLBCL non-GCB patients. And so in that case it was with the expectation based on the literature that the frequency of EZH2 mutations in that populations is exceedingly low, less than 5% and so we didn't feel the need to do so. And the classification of patients per protocol for cell of origin is based on the Hans test, which we know is a older technology that has discrepancies with what one would find for the very same patient, same tumor, same patient when one uses nanostring which is the gene expression profile that is considered to be much more accurate with respect to cell of origin. So when we gone back and retrospectively assess the patient's via nanostring, there were patients who were misclassified on both ends. So in one case, one being non-GCB when by nanostring they are in fact GCB and vice versa. For the patients who are non-GCB there were patients who turns out have an EZH2 mutation and turned out not be a surprise, because these patients by nanostring turns out to be GCB by expression profiling, but misclassified as non-GCB by nanostring. So we simply took the opportunity to move those patients over appropriately so in this reclassification analysis, which again we feel is much more accurate. That does not take away from the fact as you rightly point out that there are patients with complete responses in the non-GCB cohort and continue to be. So we are seeing activity across all the cohorts as we’ve described before, and I think as we have larger numbers and are able to report that out, it will be interesting to see what the levels of activity are within each of the cohorts.

[Robert Bazemore:]

So I think -- Peter, I will just -- I will add one thing to that comment before Peter answers the third question, which was around combination. The other two thing -- couple of things I would say is, as Peter said, we’re and you rightly point out, we’re seeing activity across all the cohorts and that’s consistent with what we saw in the Phase 1 study. But keep in mind these data are all still based on the presentation from ASH Lymphoma last year in June. So we were only a third of the way enrolled at the time that we reported these data. So we -- one of the things that we know about tazemetostat is whether they’re exhibiting a partial response for stable disease or a complete response, we know that with these drugs responses evolve over time. So we feel that in this case and particularly with an interim assessment like we did last year, both CRs and PRs are important in this population. Keep in mind that the demographics of who we're enrolling in the study they have to have at least two prior treatment exposures, but in some cases we're getting patients who have been on 5, 6, even 7 prior treatment, and so a partial response or a complete response in that patient population is clinically important.

[Geoffrey Porges:]

Yes, and I -- so, Peter or Rob, could you -- would you be willing to say of the four CRs and the three PRs out of the 35, and so that might be over 35, what proportion of those populations were GCB and ABC by the nanostring?

[Peter Ho:]

Well, the reclassification that we show in the slides that we’ve just gone through from ASH Lymphoma back in June, shows the proportions based on nanostring. So when we report out the data later in the year, we will also show what the different groupings are based on [technical difficulty] tazemetostat.

[Robert Bazemore:]

Geoff, the data that we showed in June last year was the classification, there were two versions we show, there is a classification by cohort and then there's the second slide that Peter show, which just shows the distribution by EZH2 mutational status. On the first slide, that’s the classification by Hans. There were only -- from that set of patients there were only a couple of patients who moved around, but when we present the data in June, we will show it to you both way. We will show it to you based on both Hans as well as based on nanostring. So you can see them both.

[Geoffrey Porges:]

Great. Thanks very much. And the combination?

[Peter Ho:]

Yes, to your last question, we’re [technical difficulty] there. There are many different opportunities that we see available for tazemetostat in combination and that’s driven both by the activity that we’ve seen thus far both in GLBCL and follicular lymphoma and by the very favorable safety profile that we have reported on in the past in Phase 1 and then on an interim from Phase 2 at ASH Lymphoma. So with a drug like this, that does have the safety profile that we’re seeing it really does lend itself very well to combinations with whole host of other agents, because the concern for overlapping toxicities, of course is much reduced. And then, we have spoken in the past about the clinical combinations we’ve done in lymphoma models to identify what would be the most favorable combinations moving forward and there are a variety. And indeed we agree with the point you made that there may be a particular opportunity to develop chemotherapy reduced or even chemotherapy less combinations with in agent like tazemetostat which obviously is not [indiscernible], but then combined with some of the other agents that you had earlier mentioned.

[Geoffrey Porges:]

Right. Thanks very much. I appreciate it.

[Operator:]

Thank you. And our next question comes from the line of David Nierengarten from Wedbush Securities.

[David Nierengarten:]

Thanks for taking my couple of brief questions. First off, is the patient enrollment for the lymphoma study in a mutant setting going as expected? In other words, are the timelines okay? And then I had another question on the -- again to kind of to just point thinking about the placement of tazemetostat in DLBCL paradigm that’s going to include CAR-T likely at the end of the year with an approval there. Is there any thoughts about which line of patients to focus on or which level of fitness or things like that was on the DLBCL patient population that you have? Thanks.

[Robert Bazemore:]

Okay. Yes, David, thank you for the questions. I will handle both of them. This is Rob. So in terms of the enrollment in the NHL study, it is going as we expected, as we reported late last year. We have now enrolled all three of the wild-type arms in the NHL study, those are fully enrolled and we expect to be able to present data on -- at least some data on all of those patients when we present these data in June. With regards to the EZH2 mutation cohorts, recall that these patients make up roughly 15% to 20% of the germinal center lymphoma patient population. So we never expected that these arms would enroll in the same rate as the wild-type arms enrolled. But we expect to be able to report data from both the follicular and the DLBCL cohorts with EZH2 mutations and we will have enough data to see treatment responses in both of those groups. We are actively engaging in efforts to enrich these population, so that we can find them faster than we normally would have just based on their 15% to 20% occurrence and we’re just starting to see the benefits of those efforts and we think that will help to accelerate enrollment in the mutant arms this year, but we are where we would expect to be based on the size of the patient populations. With respect to your question around [indiscernible], I think one of the things that we see in both of these programs and the patients that we're recruiting into our studies is there is clearly a significant need for new treatment options in the relapsed or refractory patient population. But I only say that these two drugs have very different profiles. Our goal which has a metastat is to be able to use it in all lines of care, including the frontline setting and that’s why we’ve begun a proof-of-concept study with R-CHOP specifically in the frontline setting. We are also looking to use it as both a monotherapy and in combinations and to Peter's point, the safety profile that we’ve demonstrated is important from that standpoint, because it allows us to combine with other drugs without significantly adding to the toxicity. We think that we can do a lot with tazemetostat because of its unique profile. Its active across a number of different tumor types. Its orally administered. Its well tolerated with very few [indiscernible] adverse events. So we look forward to discussing our financial data and registration strategies with the FDA later this year.

[David Nierengarten:]

A quick follow-up on the finding more EZH2 mutant patients. Is that expanding -- just expanding screening efforts or is there anything else that’s unique to your efforts to build versus other genetic screening efforts in other cancers?

[Robert Bazemore:]

No. So I could say two answers for the question. One, it's not changing how we’re screening for these patients. We have a test that we’re using, it’s a diagnostic developed by Roche, companion diagnostics, we're using this interface to study. It's been validated. We validated the test is accurate in terms of diagnosing patients with EZH2. So we’re not changing the house at all. The efforts that we’re doing are essentially allowing us to reach out into centers and find patients except for those or outside of those that are part of our clinical studies. So it's just broadening the net, so that we can find patients and get them into the sites and into the centers where our studies are being conducted.

[David Nierengarten:]

Okay, got it. Thanks.

[Operator:]

Thank you. And our next question comes from the line of Robyn Karnauskas from Citi.

[Srikripa Devarakonda:]

Hi, guys. This is Kripa on for Robyn. Thank you so much for taking my question. I have a question about the solid tumor program. Can you remind us how many patients will see data from -- at ASCO? And just another question about the pediatric trial in sarcoma, can you brief us on where you’re in this program and when we can expect to see data? Thank you so much.

[Robert Bazemore:]

I will start with the first question in terms of what data we have to present on the molecularly defined solid tumor program. So we plan to present efficacy, safety, and biomarker data from all the -- for all the arms of the study where we have restart futility assessment as assessed by the Independent Data Monitoring Committee. Today that includes two cohorts, epithelioid sarcoma and synovial sarcoma. We reported back in November that we had fully enrolled both of those arms. We had passed the futility hurdles and therefore we will be reporting at least on those two arms. We report on all of these other arms that have reached that futility assessment by the time of ASCO. Just to give you a sense of how we report data, the abstracts have gone in, the requirements for submission of abstracts are actually quite early for ASCO, but we plan to do an additional data cut just before the meeting so that the latest data, the latest information is available to present.

[Srikripa Devarakonda:]

[Technical difficulty].

[Peter Ho:]

[Indiscernible] this is Peter for your second question on the pediatric study stuff. This study is looking at the same groupings of tumors as in our adult type, which do include sarcomas and other INI1-negative tumors. This is a Phase 1 study with the formulation in oral suspension formulation that is being used in -- especially in the young children. So we are still in the dose escalation phase of the study now. When we complete that, we will move to the dose expansion portions of the study. But the enrollment is going on very well, we’ve had great enthusiasm amongst our investigators and we look forward to finishing up the dose escalation.

[Srikripa Devarakonda:]

Okay, great. Thank you. And if I may ask one more quick question, can you guide us to a timeline for when you might complete enrollment for the other two cohorts that EZH2 mutant cohorts in NHL?

[Robert Bazemore:]

Yes, as I said -- this is Rob. We expect, first of all, that we will have enough patient experience by the time we present these data at ICML. So really be able to assess the response rate in these patients with mutant -- with EZH2 mutation. The efforts that we’ve been putting in place to help enrich the patient populations is as I’ve said, we’ve just -- we are starting to see the benefit of those and the impact of those in terms of finding these patients faster, but we've not guided to specifically when we think we will fully enroll those two cohorts.

[Srikripa Devarakonda:]

Great. Thank you so much.

[Operator:]

Thank you. And our next question comes from the line of Mike King from JMP Securities.

[Mike King:]

Hey, guys. Thanks for taking the questions. A lot of my questions have been answered. Let me also get response well to Bob as well, I believe we are pumping [ph] one another at various conferences. Just wanted to ask you, are you guys done any work on sort of the prognostics around EZH2 mutations? In other words, have we figured out whether you know it correlates with a poor prognosis. I’m just thinking about it from a standpoint of unmet needs when you talk with the regulators about registration strategies, if you look at the various cohorts you have if there is an argument to be made that perhaps EZH2 mutants have a worse outcome than let's say wild-type and if that is a thought process that you’re going to take in?

[Peter Ho:]

Yes, hi, Mike. This is Peter. That’s a great question. And this is something that we are looking at very closely. What I can describe is that when we did take a early look at the patient demographics across all of the cohorts at our ASH Lymphoma presentation, we did see that for patients who have mutations. Remember, our patients are all in the relapsed/refractory setting not frontline patients as has been described in the literature especially for follicular lymphoma. But in the relapsed/refractory setting at least for the patients on our study who did appear for patients with an EZH2 mutation that they did seem to have more aggressive disease by a variety of parameters, the number of prior therapies they’ve received the -- the time from original diagnosis to -- through their prior therapies is coming on file. So we will be looking for characterizing that further. But I think that is very much an important question to address with respect to this population and the potential unmet need that exists there that may in fact be different from the wild-type patients.

[Mike King:]

Okay, great. Thank you for that. And then just to ask about the pipeline, have you thought about your means of communication about the next candidate, will you declare it when it's presented at a conference, will you declare it when you’ve begun IND enabling studies, I mean, how are you thinking about informing investors about the progress in the pipeline?

[Robert Bazemore:]

Mike, this is Rob. I will take that question. So as you know we said in our call that we do plan to name the next development candidate this year. The plan is that will apply for an IND and move into first in human studies next year. I think the exact timing of how we announce that will be based on a number of factors including competitive dynamics. We want to make sure that we're well protected and understanding what's going on competitively in the space before we put the information out there, but I can tell you it's a new target. It’s a new target and it’s a new indication. So we are very excited about this new development candidate.

[Mike King:]

Okay. So that’s by -- what you stated then, Rob, the -- there are preclinical talks that is going on right now for IND practice, is that a fair statement?

[Robert Bazemore:]

I think it's fair to say that the timelines that we have in place for this development candidate will be sufficient to allow us to move into first in human studies next year.

[Mike King:]

Next year, okay. Great. Thanks for taking the questions.

[Operator:]

Thank you. And our next question comes from the line of Phil Nadeau from Cowen and Company.

[Phil Nadeau:]

Good morning. Thanks for taking my questions. First let me -- my congratulations to Bob on all of the accomplishments at Epizyme and coming retirement. Just first question on the INI1-negative trial and timelines. It seems like it would make more sense for you to sit down with the FDA after the futility hurdle has been hit for all arms in the study, so is it safe for us to assume that you expect that -- all the futility hurdles to be hit by midyear and therefore probably to be hit by the time of ASCO, so we would see data from all the cohorts?

[Robert Bazemore:]

So, I don’t know that’s necessarily true and I will let Phil -- I will let Peter fill in on this question as well. The thinking is that -- again this is a conversation with the FDA to discuss the path to registration and I believe that whether we officially pass the futility hurdle in all the arms or not, that we will have enough data to be able to talk to the FDA about what we’re seeing in this program and the step to path to registration.

[Peter Ho:]

Yes, and not much more to add than what Rob had mentioned. We do want to have a meaningful conversation with the FDA and it will take the data that -- from our trial that would be useful for that, and it may or may not includes [indiscernible].

[Phil Nadeau:]

Okay.

[Robert Bazemore:]

I think our goal in this group has always been our label ultimately will be as broad as possible to cover as many of these histologies of tumors that are INI1-negative as possible. That being said, we also want to ensure that we can get the drug to market as quickly as we can for patients who might benefit from it. So our regulatory strategy is set up in such a way that we could start with single indications where we have the most experience and expand over time or go for broad label from the beginning based on the data that we’ve. So I think our strategy is flexible in that way and we still feel that midyear will be the right time to talk about the path to registration and make sure we have good alignment with the FDA.

[Phil Nadeau:]

And could you share with the FDA data from arms that hadn't hit the futility analysis or would your disclosure to them kind of -- or your presentation that will be similar to ASCO or you would only show them arms that had already passed the hurdle?

[Peter Ho:]

Right. So, what we’ve said for public presentation is that we certainly want to have data go before arm on the data monitoring committee before public presentation. Of course, our discussions with the FDA are confidential, so we would have more latitude to share the data that we’d choose to want to discuss with them.

[Phil Nadeau:]

Got it. Okay. That makes sense. And just a follow-up to Geoff Porges question, it does seem like even with nanostring, although the overall response rate is higher [indiscernible] with EZH2 mutations. The complete response rate is higher in wild-type patients and in fact that’s as of the ASH Lymphoma presentation with which we saw complete responses. How do you explain that, because it's simply wild-type patients were a bigger group more ahead of monotherapy for longer [indiscernible] or because there were possible biologic explanation?

[Robert Bazemore:]

I think it's still early. We’re certainly encouraged to see complete responses both in DLBCL and in follicular that we’ve seen throughout the entire experience of Phase 1, Phase 2. And we will have to see where that’s out. I think one thing to remember is that time dependent to end points are important, both for regulators as well as for patients. So while, I think we would certainly be encouraged to see complete responses for patients who has a partial response that is of long duration, the clinical benefits from that I would feel is at least equal if not even greater than a complete response of short duration.

[Phil Nadeau:]

Got it. Makes sense. Okay. Thanks for taking my questions.

[Operator:]

Thank you. And our next question comes from the line of Simos Simeonidis from RBC Capital Markets.

[Simos Simeonidis:]

Good morning, guys. Thank you very much for taking the questions. My first one is, I am hoping to better understand Bob's departure from Epizyme at this point. I remember meeting him seven or eight years ago and it was just Jason Rhodes and Robert Gould and [indiscernible], office in Cambridge is drawing on a white board. So he is not only the Company's CSO and Head of Research in name only, but also the person by far the most institutional memory at Epizyme let alone name, [indiscernible] space. So why is he leaving now while the Company is clearly still in the process of trying to understand your lead assets mechanism of actions, especially given what you told us today, why is he leaving before somebody is coming on board? It doesn't seem like he is leaving to become CFO -- sorry, CEO of a new exciting startup, but [indiscernible] do advisor work and that’s three months before you’re going to show us key data, which is obviously [indiscernible]. So that’s very confusing to me as somebody with a positive rating on the stock. Can you help us understand that?

[Robert Bazemore:]

Hi, Simos. Thank you for the question. And I'll -- let me start and then I will turn it over to Bob to add his comments as well, but with regard to the why in the decision, this is a part of a normal succession planning transition with high-level discussions above that actually began some time ago. Going back to last year, I can tell you that it was neither planned nor was a changed with respect to the timing of the tazemetostat data there. Essentially it's no good time for a transition like this that seems to make sense to everyone, but I can tell you that we built a very strong group of leaders across multiple discipline, who continue to work, it's been underway for some time now. We got a great team of R&D leaders that have significant tenure in the organization under Bob. As you said, he's created a strong foundation and we've amassed a lot of knowledge over the years that the Company has been in existent. So continue to drive and inform all of our efforts in the next evolution of the Company, both for tazemetostat, but also our pipeline and that’s a knowledge based, it's really hard for anyone else to duplicate. Bob as you said has been an incredible contributor to the growth and the evolution of the Company in the last eight plus years, and I think Bob is at a point in his life where he is looking for new challenges and opportunities. And I will let him explain that further, but the Company is evolving to developing novel compounds to scale at a cadence that allows to rapidly build a broad portfolio of new medicines behind tazemetostat. In terms of the actual transition, the plan is that this would continue over the next quarter. It wouldn’t be complete until the end of the second quarter. And in addition to that, Bob has agreed to remain on as an advisor to me and to Epizyme even beyond that. So that’s a bit about the rationale and I will turn it over to Bob for additional comments that he might want to make.

[Robert Copeland:]

Thanks, Rob, and thanks Simos for the kind words and the question. As Rob said, there is never a good time for something like this and I have had just an incredible experience over the last 8.5 years at Epizyme and very proud of what we've been able to accomplish on many fronts. And one of those fronts being building a very strong and resilient research organization underneath me that I feel very positive about, feel that they can carry on the important work that we’ve started. So I feel confident that my stepping away from Epizyme leaves the Company with a strong R&D capacity and I'm really excited about sharing the clinical data on tazemetostat later this year. Very proud of what we’ve been able to do with that drug, and very proud of other things in the pipeline that we will be sharing with you later on. The reality is that I’m -- as Rob said, at a point in my life where I looking for new challenges and opportunities. I haven't decided what my next move is going to be, but with [indiscernible] out of the way, I figure that Yankees might need a short stuff, so you never know.

[Simos Simeonidis:]

I think that as you’re looking for challenges, Epizyme will probably need you, can use your expertise given all you’ve done so far, but one last thing, Rob, you’ve mentioned in your opening remarks and in your answer to me that this is part of the natural evolution as you transitioning from a early stage company to, I guess a commercial organization or a company that’s developing later stage products and I would understand that if you’re at a point where you had positive data at positive meetings with the FDA and you’re ready to commercialize. I don’t think you are there yet. So this does not make a lot of sense.

[Robert Bazemore:]

Simos, I wouldn’t interpret that, Bob is retiring from the Company means that we’re not going to be bringing in new scientific leadership. I think based on where the Company is today, Bob's departure affords us a unique opportunity to think about the optimal way that we might augment our team, and our capability to support Company's long-term goals. So this is something that Bob and I’ve been discussing for some time now. We are well underway in our plans to define the new structure or our research organization and we expect to be able to share further update on that in the coming months.

[Robert Copeland:]

And Simos, just to add to that, that I’m very excited about the opportunity to continue to contribute Epizyme in an advisory role.

[Simos Simeonidis:]

Right. Thank you very much for taking the questions, and best of luck, Bob. We will miss you.

[Robert Copeland:]

Thank you.

[Operator:]

Thank you. And our next question comes from the line of Peter Lawson from SunTrust Robinson Humphrey.

[Peter Lawson:]

Hey, Rob. Just kind of thinking through the tazemetostat [indiscernible] trial that’s going on the way. How are you thinking around patient recruitment into EZH2 mutation status, is that completely enrolled to GBC status or not, just trying to go through how you’re thinking about that trial?

[Robert Bazemore:]

In which study, Peter are you referring to?

[Peter Lawson:]

The tazemetostat [indiscernible].

[Robert Bazemore:]

Yes, so this will be the new combination study that we're doing with tazemetostat and prednisolone will be specifically in patients at least for the time being who are EZH2 wild-type. We are doing this as a new cohort in the ongoing Phase 2 study. We're adding a fixed cohort to the study for two reasons. One, it allows us to get a steady up and going quickly because this is an open ongoing study. So in terms of taking a new protocol through IRB's in approval, it makes it much faster. The second is as you know we fully enroll the wild-type arms of the Phase 2 study and so if you’re going to continue to allow recruitment across the [indiscernible]. This allows us to take those wild-type patients in the arms are now closed and put them into this arm where we can answer an important scientific question. And so for the time being we will be enrolling both GCB and non-GCB, DLBCL patients who are EZH2 wild-type. We're certainly hoping to open that up later as we fill the EZH2 mutation arms we made beside EZH2 patients in the study as well, but that’s the focus for now.

[Peter Lawson:]

Thank you. And then any [indiscernible] about how you could potentially have differentiated pricing on just metostat if some of the tune that market fairness and then full of life NHL.

[Robert Bazemore:]

Yes, it’s a good question Peter and I would say that it's premature to speculate at this point on the pricing, a lot of that will depend upon the timing of the indications. It will depend upon where our actual indication look like and as you rightly know there is a lot of focus on pricing, drug pricing today. What I would say is that in this market in particular for the patient populations that we’re studying both design INI1-negative tumors which just Peter described have significant medical -- significant unmet medical need. These are patients where there is no, standard of care, nothing approved to treat them. This same in the NHL population and we’re treating these multiply refractory or relapsed patients. That we believe that innovative therapies that actually make a difference in patient lives will continue to be funded. We have to think about it smartly, but I'd say it's a bit premature to be thinking about specific pricing at this point.

[Peter Lawson:]

Got you. Thank you. And then just the necessity on the trial, when do you think you could see initial data for that -- that kind of mid 2017 or late second half event?

[Robert Bazemore:]

You know our expectation is that this year we would fully enroll the study. So we'd likely be that we’ve now report data this year. I think we will have a sense internally as to how what the signal is that we’re seeing in [indiscernible], but we likely won't report as data until next question.

[Peter Lawson:]

Great. Thank you. Thanks for taking the questions and I just like to add my congratulations to Bob as well.

[Operator:]

Thank you. And that concludes our question-and-answer session for today. I’d like to turn the conference back over to Epizyme management for any closing comments.

[Robert Bazemore:]

Thank you very much and thanks for joining the call today. It's clear we had exciting times ahead 2017 as a very big and very important year for the Company. So we look forward to updating you throughout the year on the milestones that I talked about as well reporting out the data in June. Take care everyone.

[Operator:]

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