Epizyme, Inc.
Q4 2017 Earnings Call Transcript

Published: 13 Mar 2018

[Operator:]

Good morning, and welcome to Epizyme's earnings conference call. [Operator Instructions]. Please be advised that this call is being recorded at Epizyme's request. I would now like to turn the call over to Jason Fredette, Vice President of Investor Relations. You may begin.

[Jason Fredette:]

Hello, everyone, and thank you all for joining us today. This morning, we issued a press release that details Epizyme's fourth quarter and full year 2017 results, and also summarizes the progress we have continued to make with our pipeline as well as our key milestones for 2018. This press release is available in the Investor Center of our website at epizyme.com. On the call with me today are our CEO, Rob Bazemore; and our Chief Business Officer, Susan Graf. Other members of the Epizyme team will join us for the Q&A session. Our discussion will include forward-looking statements related to Epizyme's current expectations and plans, which are subject to certain risks and uncertainties. Actual results may differ materially due to various important factors, including those described in the Risk Factors section of Epizyme's annual report on Form 10-K for the year ended December 31, 2017, which was filed this morning. This document can be accessed on our website, epizyme.com, or on the SEC's website. These statements reflect our views as of this call and should not be relied upon as representing our views as of any date in the future. We undertake no obligation to publicly update forward-looking statements. And now, let me turn the call over to Rob.

[Robert Bazemore:]

Thank you, Jason, and good morning, everyone. 2017 was a year of tremendous progress for Epizyme. During this time, we achieved many important clinical and regulatory milestones, while continuing on our path to become a fully integrated commercial organization. We generated meaningful interim clinical data with our lead product candidate, tazemetostat, in both hematological malignancies and solid tumors. We had a productive interaction with the FDA to design the registration strategy for tazemetostat for epithelioid sarcoma and identified a path to submit for accelerated approval, with our first new drug application planned for the fourth quarter of 2018. We had a positive initial interaction with the FDA regarding our registration path for follicular lymphoma, or FL, and believe we have the opportunity to submit for accelerated approval. We look forward to additional interactions with the agency throughout the year to further refine this strategy, and we're targeting an NDA submission in 2019. In 2017, we also implemented multiple initiatives to accelerate the enrollment of patients with EZH2 mutations in our ongoing Phase II study in FL and diffuse large B-cell lymphoma, or DLBCL. We advanced our solid tumor programs for adults and children with INI1-negative tumors. We completed enrollment in our mesothelioma study and surpassed the prespecified futility hurdles. And we named Epizyme's next product candidate, EZM8266, a first-in-class program targeting G9a for the treatment of sickle cell disease. At the same time, we have continued to evolve our organization to become a fully integrated biotech company, with a mission of bringing epigenetic therapies to market that rewrite the treatment paradigm and address unmet needs in cancer and other serious diseases. I'm incredibly proud of the work the entire team at Epizyme has done to bring us to this stage. Now let's discuss our programs in more detail, starting with epithelioid sarcoma, or ES. ES is an ultrarare and devastating tumor type, for which there are no targeted treatments. There are an estimated 600 patients each year in the U.S. and EU that are diagnosed with this disease, and the situation for them is dire. A diagnosis typically occurs between the ages of 20 and 40. Most people initially present with a painless mass somewhere on their body, oftentimes an arm or a leg. Without any treatments currently indicated specifically for ES, patients typically have two choices. Those with localized disease tend to undergo numerous surgeries, including potential amputations in the hopes of controlling the spread of the disease. And those with unresectable or metastatic disease are often treated with chemotherapy or may enroll in a clinical trial for an investigational agent. Overall, the median survival for these patients is reported to only be about 30 months, and it is less than one year in patients with metastatic disease. In our trial, we've observed an incredible eagerness among physicians to evaluate tazemetostat as a potential option, sometimes even before traditional chemotherapy, where there's been limited historical success in this disease. We believe this is reflective of the treating community's desire to have an effective, safe and more convenient option to provide to their patients. Based on our interim clinical activity and tolerability data, we believe tazemetostat could help address their needs. And we continue to believe this product candidate holds the potential to impact the lives of ES patients. In May of last year, we had a productive interaction with the FDA to discuss our ES registration strategy, through which we defined a path to submission for accelerated approval based on our Phase II study, which has enrolled 62 ES patients. We completed enrollment of these patients in mid-2017, and we plan to provide updated data from the fully enrolled cohort at a medical meeting in the second half of 2018. These data will ultimately form the basis for our NDA submission, which we are on track to submit in the fourth quarter of 2018. This could lead to accelerated U.S. approval and a launch of tazemetostat in 2019, which, of course, would be the most significant milestone in our company's history. To ensure we are ready, preparations for a confirmatory study to support full approval are already underway. We've also begun appropriate pre-commercial activities. These include initiating the manufacturing of commercial material, preparing the supply chain for scale-up, strengthening our network of thought leaders and patient advocates, building disease awareness to support the proper diagnosis of ES, defining our go-to-market strategy and recruiting additional medical affairs and commercial talent to ensure a successful launch. Our FL and DLBCL programs, of course, are also an important area of focus for the team. As a reminder, we are enrolling both patients with EZH2 mutations and EZH2 wild type patients in separate cohorts for both of these hematological malignancies. Starting first with FL. We kicked off 2017 by initiating patient enrollment in the U.S., and we finished the year by having our productive first interaction with the FDA to begin discussing our FL registrational approach. We're targeting an NDA submission for accelerated approval in FL in 2019. Importantly, the agency has already granted us both orphan-drug and fast-track designations for FL, regardless of EZH2 mutational status. We plan to leverage our fast-track status to interact with the FDA throughout 2018 in order to further refine our registration strategy, and we'll keep you apprised as we have meaningful updates on this front. We believe there is a clear need for a new mechanistic approach to treating relapsed or refractory follicular lymphoma. Because FL can be a more indolent disease, we know that it is important for patients to stay on drug for longer durations without detrimental side effects. Currently available treatments have significant challenges and toxicities, and patients tend to cycle through an average of 3 to 4 lines of therapy. In fact, in our Phase II study, almost half the patients received four or more prior regimens, and one patient endured more than 10 prior lines of therapy. We believe that a well-tolerated oral therapy, like tazemetostat, can make an important difference for those afflicted with FL. In terms of our ongoing Phase II study, we enrolled our FL wild type cohort in 2017, and enrollment of FL EZH2 mutation patients is expected to be completed this year. We continue to follow patients in the trial to determine objective responses, time to response and, perhaps more importantly, the durability of responses. We plan to report interim data for each of these areas from both FL populations in the mid- to second half of 2018. These data, as well as our ongoing agency interactions, will allow us to refine our registration strategy. Additionally, we intend to initiate a combination study in FL this year that will be designed to support our registration strategy. More to come on this in the second half of 2018. Now in terms of DLBCL, we expect that the monotherapy data in patients with EZH2 mutations will continue to evolve as we add new patients to the study. As is the case in FL, we intend to complete enrollment of patients this year. We also plan to present an update on our DLBCL cohorts as well as our next steps for the program at a medical meeting in mid- to second half of the year. As a reminder, we already determined that the path forward for DLBCL patients who are EZH2 wild type would be as a combination regimen. Based on tazemetostat's mechanism of action, its consistently favorable tolerability and preclinical data demonstrating combination synergies, we've initiated three combo studies in DLBCL. One is in the frontline setting with R-CHOP, which is being conducted under a collaboration with the Lymphoma Study Association. A second is in combination with atezolizumab in the relapsed/refractory setting under a collaboration with Genentech. And the third is our investigation of a combination with prednisolone, also in the relapsed/refractory patients. All of these studies are underway, and we plan to begin reporting combination data later this year. Let me now pass the call over to Susan for some further clinical updates.

[Susan Graf:]

Thanks, Rob. Let me start with our mesothelioma program. As we know, mesothelioma is among the most difficult to treat cancers. And currently, there is no standard of care after first-line treatment. In 2017, we completed enrollment of 74 relapsed or refractory patients with mesothelioma in our Phase II study. We surpassed our futility analysis, which was defined as a disease control rate, or DCR, of 35% or greater at 12 weeks. In such an aggressive tumor type, where partial and complete responses are particularly challenging to achieve and where the five-year survival rate is less than 10%, DCR is a meaningful measure of clinical activity. We are continuing to follow patients and plan to report clinical activity and tolerability data as well as next steps for this program at a medical meeting in mid-2018. Turning next to our Phase II study in adults with INI1-negative tumors. In 2017, we surpassed futility in both the malignant rhabdoid tumor and the other INI1-negative cohort. We plan to report data from these cohorts at a medical meeting in the second half of this year. Also in 2017, based on early but encouraging activity, we added a new cohort of patients with chordoma, a rare sarcoma that impacts the bone and soft tissue around the spine. This cohort, which started recruiting late last year, will enroll up to 30 patients. We expect to continue enrolling these patients throughout 2018, and we'll look forward to more fully assessing tazemetostat's potential in all of these tumor types as the study matures. From our pediatric program, we have reported preliminary data from the dose-escalation portion of the ongoing study showing responses in patients with epithelioid sarcoma, poorly differentiated chordoma and atypical teratoid rhabdoid tumors, or ATRT. These results are consistent with our adult solid tumor experience, which encourages us about tazemetostat's potential to address the treatment need for children with these devastating cancers. In 2017, we completed the dose-escalation portion of the trial, established the recommended dose, and we moved into the dose-expansion phase late in the year. We plan to complete enrollment in the second half of 2018. We also expanded our collaboration with Genentech, evaluating tazemetostat in combination with the checkpoint inhibitor atezolizumab. We initiated a Phase Ib2 study late in 2017 to evaluate this combination in non-small cell lung cancer as part of the MORPHEUS cancer immunotherapy platform. Preclinical data generated independently and by Epizyme suggest that EZH2 inhibition may enhance the immune system's ability to fight cancer through direct effects on a tumor and various immune components, and that EZH2 inhibition may also enhance the activity of checkpoint inhibitors. This combination study is designed to evaluate these effects on an inflamed or hot tumor. Given that the trial was initiated in late 2017, we expect to spend 2018 enrolling the study, and we'll work with Genentech to update time lines for data as enrollment progresses. And finally, on the clinical front. I think it's notable to point out that our tazemetostat safety database now includes more than 700 patients worldwide. Tazemetostat has been generally well tolerated across the clinical development program, which is notable relative to the safety challenges often seen with other therapies and candidates in the oncology space. We believe this could be a key differentiating factor for tazemetostat as we head toward accelerated approval submission. So as you've heard, tazemetostat represents a robust pipeline and a product opportunity, and it's one we're very excited about. We are also excited by the opportunity presented by our next product candidate, EZM8266, a novel G9a inhibitor. We know G9a plays a role in a range of blood disorders and cancers, and it is widely known that elevation of fetal hemoglobin, which is normally silenced after birth, has disease-modifying potential for patients with various beta globinopathies, including the most commonly inherited blood disorder, sickle cell disease. Based on this finding and published literature identifying G9a as an epigenetic switch responsible for turning off the production of fetal hemoglobin, we began developing a novel sickle cell treatment. Sickle cell disease impacts approximately 300,000 people globally, and its complications include stroke, vaso-occlusive crises that are associated with pain attacks, and anemia. Current sickle cell disease therapies have shown limited efficacy or have been associated with challenging toxicities, and they have been aimed at treating the symptoms of the disease. EZM8266, on the other hand, is being developed as a convenient oral therapy that's aimed at modifying the disease itself. At ASH, in December, we presented preclinical data showing that this novel G9a inhibitor elicited significant increases in mouse embryonic hemoglobin, the rodent developmental equivalent of human fetal hemoglobin. We believe these are the first in-vivo results demonstrating reactivation of developmental hemoglobin with a G9a inhibitor. We intend to complete IND-enabling studies for EZM8266 in 2018 and to initiate our first Phase I study in early 2019. In addition to all of the progress made across our pipeline, we entered 2018 in a very strong financial position. We ended the year with $276 million in cash, cash equivalents and marketable securities. We believe this will enable us to continue moderately increasing our operating expenditures year-over-year in support of our current plans and time lines, achieve many of the significant milestones we laid out today and fund the company into the third quarter of 2019. This guidance does not include any additional milestone payments or other non-dilutive sources of capital that we might receive. As we think about Epizyme's future, a key priority is, of course, to maintain the strength of our balance sheet and to support the advancement of our program, which we believe will translate into value creation for our shareholders. And so in closing, 2017 was a year of tremendous progress for Epizyme and laid the foundation for what we believe will be a transformative 2018. We are proud of the work being done by our investigators across all of our clinical programs and in our team's ability to continue Epizyme's momentum as we work to bring tazemetostat to patients as quickly as we can. We'd now like to open the call for questions. Operator, would you please provide the instructions?

[Operator:]

[Operator Instructions]. Our first question comes from Michael Yee with Jefferies.

[Michael Yee:]

Congrats on all the progress. Two questions from me. One is, in, obviously, the lead indication of epithelioid sarcoma, you've obviously presented data previously and you'll present an update that you'll presumably file with the FDA. Is data that is consistent with what you have seen before, what the FDA suggested as feedback, is minimum hurdle to get approval? How do you think about the feedback as to what would be required to get approval there? And what have they said? And then second question is on follicular lymphoma. Obviously, I'm sure we look forward to all the data this year. Can you just walk through how you suspect data would play out in mutant and wild type, and specifically what you define as good data in mutant and wild type?

[Robert Bazemore:]

Thank you, Michael, and thank you for that opening comment. We're very pleased with the progress that we made in 2017. We think the accomplishments line up directly with the guidance that we had set at the beginning of the year. And of course, even more excited about the year we have this year with the regulatory and clinical milestones we have ahead of us and our filing of our first NDA. With regard to epithelioid sarcoma, our expectation is that we'll present data in the second half of the year. The reason that, that -- the way that timing lines up is we want that data that we present at a medical meeting to be consistent with the data that supports the NDA package that we'll be submitting to the FDA for approval. Our understanding from the discussion we had with the FDA last year, in May, when we talked about a path to registration and an accelerated approval opportunity, was that the data across the entirety of the cohort of 62 patients would be consistent with or better than the data we saw in the first 30 patients. And you'll recall from those data at that time we had seen a 30-ish percent response rate -- disease control rate over eight months. Or at the same time, we had seen a 13% objective response rate. And we were still waiting for the durability of data to mature there. But our conversation with the FDA was that, that data would be sufficient to support a filing for an accelerated approval, and we're just waiting on the cohort of the additional 31 patients now, total of 62 patients, on which to file. That cohort was completely full as of July, and so that gives us confidence that, with those data maturing, we'll be on -- in a great position to submit the NDA in the fourth quarter of the year, this year. With regards to the follicular lymphoma program, this is an ongoing study. As you know, we're still enrolling patients who have EZH2 mutations. We're still seeing the data evolve in both groups of patients, because even in those patients who had EZH2 wild type disease, although they were fully enrolled last year, we're still following those patients for durability, and a number of those patients remain on study. So we have some precedents, I think, that have been set in the marketplace in terms of what recent -- have been more recently approved products. The PI 3-kinase, as an example, which have shown response rates in the 50-ish percent range. However, this is a new mechanism with a completely different benefit-risk profile. And in addition to overall response rate, things like durability, safety and tolerability, particularly in follicular lymphoma patients who tend to stay on their medications for longer periods of time, will all be important, we think, to how the FDA assesses this new therapy. So we look forward to those ongoing interactions with the FDA this year to further refine our approach to an accelerated approval filing in 2019.

[Michael Yee:]

Just as a follow-up to that. In the wild type group, do you think that there is a different way that the agency looks at it as a genetically defined population as opposed to just a broad population so it might be considered differently there? And as you're still enrolling, what has been the issue there? And what have you been doing to accelerate enrollment, how confident you are that you're going to get that enrollment done? I would think, as a defined population, you could find these patients.

[Robert Bazemore:]

So good question, Michael. Good questions. I don't think that the agency looks at these populations differently. I mean, we split them into two cohorts because we wanted to see the differences in therapeutic effect between patients who had a mutation and those who didn't. But this is the first time, to our knowledge, that a product has been presented to the FDA for registrational purposes, where patients were defined based on a mutational status as we're doing with EZH2. So we don't think the FDA automatically looks at it that way. With regards to enrollment, we're making great progress there. As you know, after the data were presented at ICML last year, we put a number of new initiatives in place on the heels of actually having the data to help us be able to screen patients more quickly. These were things like engagements with US Oncology. There are others that we haven't press released, but we've formed collaborations with other oncology groups, like Sarah Cannon and others. We've gone into new sites in Eastern Europe. So there are a number of things that we've done to allow us to find these patients more quickly. Our guidance is that we expect to have the study fully enrolled this year and that, that would support a filing in 2019.

[Operator:]

Our next question comes from Geoffrey Porges with Leerink.

[Geoffrey Porges:]

Some follow-up clarification questions, if I may. First is, if you get to full enrollment this year for the EZH2 mutant DLBCL and FL patient population, what would that population look like? How many patients will you have, Rob? And then secondly, in your press release and in your comments, you said that there would be a confirmatory study in both ES and, I think, in follicular lymphoma. And could you explain what those confirmatory studies look like and then what the sequence would be? Would those studies need to be initiated before you file or initiated before you get an approval? Does the FDA -- are they going to need to see the data before approval? How is both filing and approval going to be sequenced with those additional studies?

[Robert Bazemore:]

Thank you for the questions, Geoff. I'll address the first one with regards to the size of the patient cohort. So in follicular lymphoma, each of the cohorts were designed to be 45 patients. We slightly overenrolled the wild type patient population last year, but it was designed to be 45 patients, and the same is true of the mutant cohort. So when done, this would be at least 90 patients with follicular lymphoma. For diffuse large B-cell lymphoma, each of these cohorts were designed to be 60 patients. Recall there were three DLBCL cohorts. There was germinal center, non-germinal center wild type, and then the EZH2 mutated. So it'll be a total of 180 patients with diffuse large B-cell lymphoma when all three of the cohorts are fully enrolled. With regards to the confirmatory study, you're familiar with the fact that whenever you're filing for an accelerated approval, there's always an obligation to do a confirmatory study for full approval. So when we talk about a confirmatory study, it is just that. It's a study that would guarantee full approval of the product. There is no real hard and fast rule on when it has to begin. The FDA likes to see a good faith attempt to get the study started. Oftentimes, they like that the study is already enrolling patients by the time the approval is granted. It's not a requirement, but they like to see a good faith -- that the company intends to start and actually finish the study. But that's generally the guideline.

[Operator:]

[Operator Instructions]. Our next question comes from Andrew Berens with Morgan Stanley.

[Andrew Berens:]

Maybe a question on the combination data in DLBCL. It sounds like 2 of the 3 trials are not company-sponsored. Can you just walk us through, I guess, what type of data we can expect from those trials? And if you can give us any potential benchmarks of what you think would be a successful outcome for those trials, it would help.

[Susan Graf:]

Sure, Andy. This is Susan. So I'll start with the R-CHOP combo in the frontline setting. So this is a combination study that's being run by the French lymphoma consortium LYSA. This is a two-part study. It was the first time we ever combined tazemetostat with the chemo regimen R-CHOP, so there was a Phase I dose-escalation portion, followed by what will be a Phase II efficacy evaluation portion. So when we first present data from this study, you should expect that it's just going to be data from the Phase I dose-escalation portion, and that would obviously be focused around safety, tolerability and PK of tazemetostat plus R-CHOP. Of course, there is an efficacy assessment associated with that, but it will be a small number of patients with the primary endpoint really being the safety and tolerability of that. The efficacy data, again, it's frontline DLBCL, so these are patients who are likely to be on therapy for longer. So that will not be a 2018 event in terms of the efficacy analysis. In terms of the next collaborator combo, we have the Genentech collaboration in diffuse large B-cell lymphoma with atezolizumab and tazemetostat. This is a relapsed/refractory all-comer patient population. This, when the data are presented, will show both safety and tolerability of the regimen, but also the real efficacy assessment in terms of ORR. So we'll be working with Genentech to find the right form and timing for presentation of those data. And then lastly, in terms of prednisolone. This is a study that, as you recall, we added to our ongoing Phase II study. And we have full control of this cohort. These are data that we were relying on that preclinical synergy we had seen with prednisolone, as well as the hope that prednisolone would help arrest the aggressiveness of diffuse large B-cell lymphoma. So those data, again, will look at overall response rate in a relapsed/refractory diffuse large B-cell wild type population.

[Andrew Berens:]

Okay. And is there any benchmarks we should look at for any of those combinations?

[Susan Graf:]

The benchmarks in the relapsed/refractory setting, we could look at our own [indiscernible].

[Susan Graf:]

Final data there yet, but we do view that as relevant. On atezolizumab combo, I would say, checkpoint inhibitors are not commonly known to work in cold tumors, so that I can't provide you a good benchmark. And R-CHOP frontline, the population we're going into is an elderly high-risk population that are -- that tend to be less responsive to R-CHOP alone. So somewhere in the 60% to 70% response rate to R-CHOP as opposed to higher in that population. So when we ultimately get to the efficacy portion there, we'll be looking for a 10% improvement in the complete response rate in frontline patients.

[Andrew Berens:]

Okay. I appreciate the color. And then just maybe a question on the rationale of combining tazemetostat with PD-1 or PD-L1. And some of this you may not know, but what is the rationale that it could add to better efficacy?

[Susan Graf:]

So it actually comes down to the role, we believe, EZH2 inhibition plays in the cancer immunity cycle. We do believe that EZH2 inhibition allows both tumor priming as well as immune cell trafficking to the microenvironment that make tumors and the microenvironment more responsive to checkpoint inhibitors. So there's preclinical data by Epizyme and others that suggest this is true, and we're testing the clinical experiment here. And I would actually just add that we started with diffuse large B-cell, which is a cold tumor, and that study is obviously farther along. But we started -- at the very end of 2017, we opened for enrollment our collaboration with Genentech in relapsed/refractory non-small cell lung cancer. So that's the hot tumor clinical experiment now that we're running.

[Operator:]

Our next question comes from Robyn Karnauskas with Citi.

[Robyn Karnauskas:]

So a couple. So just walking through a little bit more about the execution that you have to do before you're able to come to market. Where are you with CMC? And what are the biggest hurdles? And then also, like how many people would you have to hire? And when would you hire them? Are you going to hire them this year? Or you think a lot of the expenses would be next year?

[Robert Bazemore:]

Robyn, yes. So there are a number of steps that we plan to go through as we prepare for the NDA, all of which we believe that we're on time for. There are a number of conversations that have already happened. And when we had our meeting back in May of last year to talk about registrational strategy, there are a number of things that go into that. It's not just a discussion of the clinical data, but it's a discussion of the program overall, which includes nonclinical, clinical pharmacology, CMC, there are a number of parts of that discussion. So we feel like with all of those things having been discussed, we have a line of sight to an NDA submission in the fourth quarter of this year. There are a number of things that we'll be doing to prepare for the launch at ES. Many of them are starting some of the precommercial efforts, which includes things like initiating manufacturing of commercial material, preparing the supply chain. The lead times on that are quite long, so as you might imagine, that already begun even last year. Strengthening our networks with thought leaders and patient advocacy organizations so that we can educate the market on epithelioid sarcoma, the appropriate diagnosis of ES and making sure that these patients who are diagnosed find their way to tazemetostat. And then in terms of hiring, the places that we would anticipate, for this year, starting to do additional hiring would be in the commercial and primarily the medical affairs areas, as we think about educating the market on this disease and the appropriate diagnosis. We think this is an indication we can launch with a relatively small commercial footprint. If you think about it, these patients tend to end up in specialty treatment centers that we think that we can address with a relatively small footprint.

[Robyn Karnauskas:]

Great. And what bar would you set for mesothelioma for your filing or FDA's willingness to even look at your filing?

[Robert Bazemore:]

It's a good question, and it's one that's kind of hard to gauge because there have not been any products approved for mesothelioma in relapsed/refractory disease, which is what we study. There is a standard of care in the frontline setting, but we use disease control of 35% or greater at 12 weeks because we think that's a good indicator of clinical activity. If you recall, the 10-year or the five-year survival of these patients is less than 10%. So we think that a DCR, as we've established, is a good marker to establish clinical activity. So we're very pleased that we crossed that threshold and passed futility. But in terms of what suffices for registration, I think the bar will be relatively low, but we've not engaged with the FDA to talk about any registrational paths or activity for tazemetostat as of yet.

[Operator:]

Our next question comes from Peter Lawson with SunTrust Robinson Humphrey.

[Peter Lawson:]

Just on the 31 additional epithelioid sarcoma patients, is there a difference in that patient group versus the initial cohort? And do you think that could, either positively or negatively, affect the response rate or DoR? Any thoughts around that would be appreciated.

[Robert Bazemore:]

Thank you, Peter. It's a good question, and we've been asked this a couple of time before. We have no reason to believe that the patients that we've enrolled or the outcomes of those patients should be different from the first 31. Essentially, the enrollment criteria were the same. The only thing we changed was we wanted to make sure that we had people with active disease coming into the study. We didn't want there to be any criticism by the FDA that we had enrolled patients who had stable disease and, therefore, any benefit that we reported was due to that, not the benefit of the drug. So we required patients in the second 31, the second part of the cohort, to have ongoing active disease. We went back and looked at the first 31 patients and in fact established that almost all the patients in the first 31 had that. So it's -- there's no reason to believe that, that would in any way change the outcomes or the severity of illness in the patients in the second 31 compared to the first 31. So there's no reason we have, looking at it today, to say that the outcomes in the second 31 should be different.

[Peter Lawson:]

And that kind of severity of the active disease, when you went back and looked at the first, kind of looks in line with the enrollment you're seeing in that second cohort.

[Robert Bazemore:]

It does. Yes, Peter. Almost everybody in the first cohort of 31 had active disease. Physicians tend not to enroll patients into clinical trials onto investigational drugs when they have stable disease.

[Peter Lawson:]

Got you. That's really helpful. And then, Susan or maybe Rob, just on this combo data. Do you get any sense of which sets will read out first, whether it's the R-CHOP or the Tecentriq or prednisone?

[Susan Graf:]

So Peter, I think the one that we have control of, the timing of data presentation is the prednisolone combo. So that's the one we can commit to starting to present data in 2018. We obviously have to work with our collaborators on presentation of the other studies. So we'll be able to update you as we know more information ourselves.

[Operator:]

[Operator Instructions]. Our next question is a follow-up from Geoffrey Porges with Leerink.

[Geoffrey Porges:]

I just want to confirm on meso. Could you let us know or remind us at least the proportion of mesothelioma patients that you're finding that have BAP -- the BAP1 loss of function mutation and then just confirm the number of patients enrolled or on drug and a little bit about their treatment history? Are these first-line patients? Or have they already been exposed to chemo?

[Robert Bazemore:]

So yes. It's a couple of good questions, Geoff. On the patient population, if you look at published literature, the demographics would suggest that patients who have loss of function of BAP1 should be about half of the patient population. We had a run-in to this study, which was a clinical pharm -- we wanted to do clinical pharm testing on the first 10 patients or so that came into the study. The majority of the patients that came in were actually BAP1-negative. It wasn't 50-50. It was the majority. Now you could argue there's some bias to this because we're looking -- there was a knowledge that we were going to ultimately be looking for patients who have loss of function of BAP1. But the published literature suggests it's about half the patient population, which you know is about 12,000 newly diagnosed patients per year. The patients that we're studying in this study are all relapsed/refractory patients. There is a standard of care in the frontline setting. It is a platinum chemotherapy and Alimta in the frontline setting. So these are all patients who failed frontline therapy and/or maybe something else in the second-line setting.

[Geoffrey Porges:]

Great. That's very helpful. And the patient numbers that you have enrolled?

[Robert Bazemore:]

The total is just over 60. We had planned for a cohort of around 60 people, and the cohort was overenrolled.

[Susan Graf:]

And adding the clin pharm portion, which was about 12 patients. So we have a total of 72 patients enrolled.

[Operator:]

Our next follow-up comes from Peter Lawson with SunTrust Robinson Humphrey.

[Peter Lawson:]

I know this is kind of an early question, but anything you can say around pricing would be helpful. Just with the idea that you've got potentially multiple approvals in different indications coming up and -- should we think about that as a single price point? Or how are you thinking through this as -- is there a possibility of having differentiated pricing for those different indications? Any color around that, we'd be grateful.

[Robert Bazemore:]

Sure. I'd be happy to. And I'll go back to the first part of your question, which is it is a little bit early. Obviously, our pricing strategy will depend upon our ultimate label that we get. And I think strategy also depends upon the timing of how far apart these indications are. We're fortunate in that we have the opportunity to submit two NDAs in back-to-back years. So with that being the case, we'd expect these indications to come relatively close to each other. So in that case, we tend to think of it as what is the price that takes advantage of having effectiveness in a disease like epithelioid sarcoma, a rare disease, hard-to-treat patient population where nothing else is approved to treat them. But also recognizing that we don't want to price ourselves out of the follicular lymphoma or diffuse large B-cell lymphoma market, if we expect an approval to come time -- sometime shortly after. Although there is a great desire to look at pricing by differential indications, my experience has been that that's -- it's still a ways in the future. It's kind of hard to achieve that with a single product. Unless if the product is split into different brand names, that's hard to do. So we would ultimately look at what do we think is the right price point for tazemetostat given the two indications that I just discussed and the proximity of those on each other. But it's still early. We're doing a lot of the work now. Ultimately, it's going to depend upon the strength of the data that we see, and much of that data you'll see this year, in the mid to second half of the year, and ultimately our label in those two indications.

[Operator:]

I'm currently showing no further questions at this time. I'd like to turn the call back over to Rob Bazemore for closing remarks.

[Robert Bazemore:]

Thank you, operator. We're very excited about 2018. 2018 is set to be a big year for Epizyme. And we look forward to reporting back to you on the many significant milestones that we have ahead of us. So thank you, again, for joining us today. Take care, everyone.

[Operator:]

Ladies and gentlemen, this concludes today's conference. Thanks for your participation, and have a wonderful day.