Syndax Pharmaceuticals Inc (SNDX) 2018 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Syndax First Quarter 2018 Earnings Conference Call. (Operator Instructions)

I would now like to turn the conference call over to Ms. Melissa Forst with Argot Partners. Ma'am, you may begin.

Thank you, operator. Welcome, and thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax's first quarter financial and operating results. I'm Melissa Forst with Argot Partners, and with me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer; and Rick Shay, Chief Financial Officer. Also joining us on the call today for the question-and-answer session is Michael Metzger, President and Chief Operating Officer of Syndax. This call is being accompanied by a slide deck that has been posted to the company's website. So I'd ask you to please turn to our forward-looking statements on Slide 2.

Before we begin, I would like to remind you that any statements made during this call that is not historical is considered to be a forward-looking statement within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section of the company's most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today, May 8, 2018, only. A replay of this call will be available on the company's website at syndax.com.

And with that, please turn to Slide 3, and I'm pleased to turn the call over to Dr. Briggs Morrison.

Thank you, Melissa, and thanks to everyone joining us on today's call and webcast. This afternoon I'll share the progress we've made during the first quarter as we continue to execute on our corporate strategy in support of our primary mission to realize a future in which people with cancer live longer and better than ever before.

Slide 3 briefly summarizes our corporate strategy, which includes developing 3 potential best-in-class molecules, entinostat, SNDX-6352 and our Menin-MLL-r portfolio, which are being tested at 5 ongoing clinical trials across 6 different indications. An additional important component of our corporate strategy is the opportunistic in-licensing or acquisition of products that have both a compelling strategic fit and potential return on our investment.

Slide 4 provides a summary of the investment highlights for Syndax. During this call, I will primarily focus on the progress we're making with our lead program, entinostat. I will discuss both our Phase III trial for breast cancer, which we received breakthrough therapy designation from the FDA as well as our exciting ENCORE clinical trial program, which combines entinostat with PD-1 antagonist.

Slide 5 provides a summary of the milestones we communicated on our last call back in March. I will say more about the abstracts we will be presenting at ASCO later in my comments, and I will note that we now anticipate top line results from ENCORE 602 in the first half of 2019.

Let me now turn to Slide 6 and give you an update on E2112, our Phase III trial of entinostat in hormone receptor-positive, HER2-negative breast cancer. Slide 6 summarizes the trial design and end points. We've also summarize the key upcoming milestones.

As we communicated previously, in the fourth quarter of last year, the ECOG Data Safety Monitoring Committee completed the final progression-free survival or PFS analysis and the first interim overall survival or OS analysis of this trial.

These analyses are held confidentially by the ECOG-ACRIN study statistician and the data safety monitoring committee.

No communication regarding this analysis will be released until the completion of enrollment.

We've recently learned that the ECOG data safety monitoring committee has now also completed the second interim overall survival analysis of the trial, and the trial is now 90% enrolled as of the end of April.

We anticipate enrollment completing sometime in the third quarter of this year and will continue to update you about the precise timing of completion of the trial as its final enrollment progresses.

Once enrollment is completed, we will learn of the results of the final PFS analysis; and if positive, we're poised to file an NDA by the end of this year.

We received many questions about what exactly will be communicated at the time of completion of enrollment.

And so just to clarify, if the PFS analysis is statistically significantly positive, Syndax will communicate top line results and present full data at an appropriate medical meeting.

If the PFS analysis is not positive, Syndax will not receive any data from the trial and will simply communicate that PFS was not positive and indicate when the next interim OS analysis will be conducted.

Indeed, I'd like to remind you that the data safety monitoring committee will examine updated overall survival every 6 months, generally in May and November.

Should any of the interim analyses of overall survival show a statistically significant benefit, the trial will end, and all data will be released to ECOG and Syndax.

We would again communicating top line results and present full results at an appropriate medical meeting.

We remain confident in the potential outcome of E2112 given that it's based upon strong Phase II data, which led to FDA breakthrough therapy designation.

Slide 7 emphasizes the potential for the entinostat-exemestane regimen to become the preferred agent after a CDK4/6 therapy for hormone receptor-positive, HER2-negative breast cancer.

We know that CDK4/6 therapies, most notably Ibrance, are being used increasingly as first-line agents. But there's a clear desire to understand what therapies will be effective in a patient who has stopped responding to a CDK4/6 inhibitor.

Our current estimate is that between 30% and 50% of patients in E2112 will have received a CDK4/6 inhibitor prior to entering the trial, and thus, we will have a highly relevant data set in this population.

And importantly, as shown on Slide 7, we have tested entinostat in 3 distinct preclinical models of palbociclib resistance and have found no cross-resistance with entinostat.

That is, the median effective dose of entinostat in these model systems is the same whether or not the cell line is resistant to palbo.

This preclinical data suggests that the fact that patients have received a CDK4/6 inhibitor prior to entering E2112 should not affect the ability of entinostat to provide a clinical benefit.

Together, we believe these data uniquely position entinostat to be the preferred agent after CDK4/6 first-line therapy.

Slide 8 makes the same point and notes that this population of patients is relatively large, with an estimated 34,000 patients who go on to receive hormone therapy after failing first-line therapy and could, therefore, potentially be able to receive the entinostat-exemestane regimen.

Let me now turn to Slide 9, which summarizes our exciting ENCORE clinical trial program in which we are testing entinostat in combination with PD-1 pathway antagonists, either PD-1 antibodies or PD-L1 antibodies.

We are now exploring entinostat in combination with a PD-1 antagonist in 6 different tumor types, melanoma, non-small cell lung cancer, microsatellite stable colorectal cancer, triple-negative breast cancer, ovarian cancer and hormone receptor-positive breast cancer.

This broad clinical trial program is supported by an extensive correlative science program that is designed to identify biomarkers that could predict which patients will experience a clinical benefit from our combination therapy, an effort that is starting to yield exciting preliminary results.

We are extremely encouraged by the results we are seeing across this clinical trial program, and as we complete our initial clinical trials in each tumor type, we will prioritize which indications to advance to registration trials based upon unmet medical need, the competitive landscape and our ability to generate an attractive return on our investment.

Slide 10 is a summary of where we are with our program in melanoma. We presented the initial cohort of 13 patients at ASCO in 2017, where we saw a 31% response rate.

Based upon continued discussions with melanoma physicians, it's clear that a response rate of about 20% or greater would be considered highly clinically relevant, especially in patients whose disease has progressed after receiving both a PD-1 antagonist and a CTLA-4 antagonist.

Given the tremendous enthusiasm with this combination from our investigators, we've allowed continued enrollment in this cohort of patients and have now enrolled a total of 55 patients. We'll present an update on this cohort at ASCO.

Given that we have now conducted our regulatory consultations and a number of advisory boards with physicians experts in the treatment of melanoma, we will be providing details on our registration strategy sometime later this quarter.

Slide 11 is a summary of where we are in that program in non-small cell lung cancer. We presented the initial cohort of 31 patients whose disease had progressed on a PD-1 antagonist at SITC in November of 2017. The response in that cohort was 10%, and we've continued to receive very strong feedback from physicians participating in this trial.

As I noted earlier, we're making exciting progress with our extensive correlative science program designed to identify biomarkers that could enable us to enrich for patients who derive clinical benefit as we design future clinical trials. We've allowed continued enrollment in this cohort to aid in our biomarker discovery effort and have now enrolled a total of 76 patients. An update on this cohort will also be presented at ASCO. ASCO abstracts will be released next week on May 16. It's important to note that these abstracts were submitted in early February with the data cutoff as of late January. And I want to emphasize that our non-small cell lung cancer abstract has no information about our biomarker work. That work has just come together in the past couple of months. Data from the biomarker analysis will be included in our poster, and we're excited about this new data and look forward to sharing it with you.

Slide 12 highlights 2 points. The first is that biomarkers are routinely used today to select the most appropriate therapy for patients with non-small cell lung cancer.

Outside of immuno-oncology, tests for EGFR mutations and ALK rearrangements are now routine, and there are a number of commercially successful therapies that are specifically used for patients with these genetic lesions.

KEYTRUDA, of course, is indicated as monotherapy for newly diagnosed non-small cell lung cancer patients with high PD-L1 expression. And BMS recently communicated that tumor mutational burden may be a marker to select newly diagnosed patients who benefit from the combination of Opdivo and YERVOY.

So based upon this established approach to treating non-small cell lung cancer, we are focusing our efforts on developing a patient selection strategy that will enable us to enrich for a specific population of patients as we progress development of entinostat in non-small cell lung cancer. The second point is that the treatment paradigm for non-small cell lung cancer is becoming clearer as a number of Phase III trials have read out.

The data from KEYNOTE-189 trial suggests that all patients regardless of PD-L1 status may derive a benefit in terms of overall survival when treated with KEYTRUDA plus chemotherapy compared with platinum-based chemotherapy alone. And data would suggest that the KEYNOTE-189 regimen will increasingly be used in the first-line setting.

One should know, however, that in KEYNOTE-189 roughly 80% of patients have progressed within 18 months of starting therapy, and these patients are today treated with standard single agent or combination chemotherapy. We believe there is a large and growing unmet need in this population of patients for improved therapy.

Slide 13 is a summary of where we are with our program in colorectal cancer. We completed enrollment of the first cohort of patients at the end of the third quarter last year and are continuing to monitor these patients. We'll present data on that cohort at ASCO. However, in collaboration with Merck, we have modified the Simon 2-stage design for colorectal cancer. Initially, this cohort was designed with 13 patients in stage 1 and a criterion to have at least 2 responses in order to move into stage 2 and then enroll a total of 34 patients. That design was based upon a predictive response rate of 25% for the overall cohort.

As we noted in our last call, based upon continued discussions with physicians that are expert in the treatment of colorectal cancer, it's clear that a response rate of even 15% would be highly clinically relevant in this population of patients. So we've therefore modified the Simon 2-stage design to test for a predictive response rate of 15%.

We will thus enroll a total of 37 patients in stage 1, and if we see at least 3 responses, we'll proceed to stage II, enroll an additional 47 patients for a total of 84. We will commence enrolling this modified stage 1 cohort later this quarter, anticipate making a go/no-go decision to advance to stage II in the first half of 2019. I should also again emphasize that we're exploring a number of biomarkers in this cohort, with the goal of, again, finding a way to enrich for patients who derive clinical benefit.

Slide 14 makes the point that microsatellite stable colorectal cancer represents a significant market opportunity for entinostat if we can demonstrate efficacy in this clinical setting.

Slide 15 summarizes ENCORE 602 and 603, our Phase III trials in triple-negative breast cancer and ovarian cancer. I'm pleased to report that ENCORE 603 has completed enrollment, and ENCORE 602 should complete enrollment this quarter. We now anticipate top line results from both ENCORE 602 and 603 in the first half of 2019.

So again, we're very pleased with the breadth of our ENCORE clinical program and the excitement we are sensing from physicians who are conducting these important clinical trials.

Let me now turn to Slide 16 and SNDX-6352, our potential best-in-class monoclonal antibody targeting the CSF-1 receptor.

We presented the Phase I healthy volunteer data at SITC in November of 2017, and the MAD study in cancer patients is ongoing.

In January of this year, we were very pleased to announce our collaboration with AstraZeneca to study the combination of 6352 with IMFINZI.

Initial work focusing on establishing the safety of this combination is expected to begin this quarter, and we've now designed a very focused clinical development program for this molecule, and we'll say more about that later this year.

Slide 17 summarizes our Menin-MLL-r program, which spans a broad range of leukemias and potentially other indications as shown on the slide.

We remain on track to file an IND in the first half of 2019.

Data was presented at AACR regarding demonstrated efficacy both in MLL-r PDX models as well as in NPM1 mutant PDX model. And these presentations can be found on our website.

Slide 18 summarizes how the transactions that we completed to acquire both SNDX-6352 and the Menin-MLL-r programs prove that we have an ability to strategically expand our pipeline.

Our management team and board have established relationships that allow us to identify quality assets, and the extensive clinical development experience of our team gives us a competitive advantage in closing agreement.

We continue to expend significant effort in this area, and we consider this capability to be a core strength of our company.

On Slide 19, we summarize the data that will be presented at ASCO, and we look forward to seeing many of you there in Chicago.

And with that, I'll turn it over to Rick for the financial update.

Thank you, Briggs.

Turning to Slide 20. For the 3 months ended March 21, 2018, Syndax reported a net loss of $19.4 million or $0.79 per share compared to $13.0 million or $0.71 per share for the prior year quarter.

First quarter 2018 R&D expenses increased to $15.3 million from $9.6 million for Q1 2017.

The increase was primarily due to increased CMC development activities for SNDX-6352 and to initiating work on our Menin program.

These increases were partly offset by completion of several entinostat Phase I clinical pharmacology trials and a decrease in E2112 costs.

General and administrative expenses totaled $4.8 million during the first quarter of 2018 compared to $3.9 million for the prior-year period.

The increase in G&A was primarily due to increases in headcount, professional fees and patent-related legal expenses.

At March 31, 2018, there were 24.7 million common shares outstanding. And on a fully diluted basis using the treasury stock method, we had 26.2 million shares.

Additional financial details will be available in our 10-Q report, which we intend to file this week.

Syndax ended the first quarter of 2018 with a cash balance of $113 million, which we believe is sufficient to fund development into 2019, enabling us to reach key development milestones.

And looking ahead, we expect R&D expenses to be $15 million to $18 million for the second quarter and $62 million to $70 million for the full year.

And total operating expenses are expected to be $20 million to $23 million for Q2 and $82 million to $90 million for the full year 2018.

And now I'd like to turn the call back to Briggs.

Thanks very much, Rick. So looking ahead, we anticipate several key upcoming milestones summarized on Slide 21.

I've already discussed the upcoming data presentations at ASCO and the readout of the PFS results from our Phase III trial in hormone receptor-positive, HER2-negative breast cancer, E2112.

As I noted in my previous comments, the top line data from ENCORE 602 and 603 are now both anticipated in the first half of next year, and we anticipate being able to decide to expand the modified colorectal cohort around the end of this year or early in 2019.

With regards to SNDX-6352, we look forward to sharing both the data from our multiple ascending-dose trial and the details on our clinical development strategy. It's obviously going to be a busy year for us here at Syndax.

As always, I'd like to thank the team here at Syndax. I'd like to thank our collaborators and, most importantly, the patients, the trial sites and investigators involved with our clinical programs.

With that, I'll open up the call for questions.

(Operator Instructions) The first question is going to come from Chris Shibutani from Cowen.

(inaudible) many different clinical updates coming for you, especially at ASCO. We're just now coming off the heels of AACR as well. You didn't mention, but there were some early data that was presented there talking about entinostat in combination with NKTR-214. I know that the folks at Nektar have commented upon that and seem to express some enthusiasm there. Can you highlight some of the takeaways and what you're thinking about, what kind of structure we might be able to see you continue to develop that work, how that might play out?

Chris, so what we presented at AACR was a preclinical combination work done with NKTR-214 and entinostat, and I think quite interesting combination therapy. We're continuing -- we set up that collaboration with Nektar sometime ago, and we're continuing discussions with them about how we can bring that combination into the clinic and see if the preclinical findings translate into clinical advance as well. So those conversations are ongoing. We can't comment on whether it'll come to fruition or not, but we are having conversations with them.

The next question comes from David Lebowitz from Morgan Stanley.

Out of curiosity, given where you are with non-small cell and in refractory and with data before that was in the naive, I guess, what are the overall thoughts going forward in non-small cell as what might the next steps be?

Thanks, David, for your question. So you're correct that in the initial design of ENCORE 601 we had a cohort of naive patients and we had the cohort of refractory patients. In both cases, we met the criteria to expand the cohorts. We decided not to do that in the naive patients because we were waiting for the results of some of the large ongoing Phase III trial. I think in retrospect that was probably a good decision given where things have sort of landed with the readout from the KEYNOTE-189 trial. And as I tried to sort of allude to in my comments, I think our focus is more on the patients who have progressed on both chemo and the PD-1. We think that's the growing area of unmet need, and so our efforts right now are completely focused on that refractory population, and at this stage, we are not progressing additional studies in the naive population.

Sure. And you were also -- in colorectal cancer, you were talking about the modification in the trial. Could you just go through the rationale behind the initial 25% threshold that was selected and how it has moved to 15%? What you learned from physicians versus what you had thought before?

Sure. So the initial design, the 25%, was essentially a copy of what we had done in melanoma, aiming to be highly relevant with a high response rate. We continued to have a lot of conversations with colorectal physicians as that trial was enrolling and got feedback that for sure if you hit 25% that would be quite interesting, but you guys shouldn't -- not be interested in something that has perhaps a lower response rate given how important it is to find new agents in this area. And compared to some of the other agents that are used in this area, they thought even 15% would be of interest. And I noted on our last call that we -- it's an open-label trial. We have seen activity. And so we went back and had a conversation with our collaborators and with the investigators and said maybe we should modify this so that if the true response rate is 15% we have sufficient power to be able to detect that and to characterize that and to make sure that we have a sufficient number of patients that we can also do the biomarker analyses. So that was the reason to expand the colorectal population and to change the thresholds for the study.

The next question comes from Konstantinos Aprilakis from JMP Securities.

This is Simon Gruber on for Konstantinos. Just a real quick question. The E2112 PFS data coming in Q3, just wondering if there is any accompanying data that we can expect? Or if it will just be like a top line PFS number?

Right. So Simon, thanks for the question. At the time that the data is released -- so if the PFS result is positive, we'll get the data set from ECOG and, obviously, be in the process of getting ready to put together the NDA. Our anticipation is that the initial communication from the company would really just be top line results, and we would look for an appropriate medical meeting to go through all the details around both efficacy and safety.

Next question comes from Bert Hazlett from BTIG.

Looking forward to all the readouts upcoming here. Briggs, could you just describe some of the considerations? I know you'll give us more granularity with regard to the filing strategy in melanoma, but just some of the considerations that are at play for that particular PD-L1 refractory melanoma population?

Yes. Sure, Bert. So I think as we may have talked about previously, there is essentially -- we think of it as 2 different populations. The patients there are patients today who are being treated with a PD-1 antagonist as a monotherapy and -- their first therapy and then subsequently may receive CTLA-4 ipilimumab. And then there are other patients who are treated with both agents right upfront. At the end of the treatment regimen, essentially you end up with a cadre of patients who received both the PD-1 and a CTLA-4 and are refractory to both. That population is likely to be the area of highest unmet need. Those patients generally go -- I mean, if they're still suited, then they'll go on to chemotherapy. The patients who have gotten a PD-1 monotherapy as their first treatment and have not yet received a CTLA-4 antibody are slightly different, where from a regulatory and clinical point of view people would want to know how does the agent compare to treating it with ipi as -- for example. So we think of those as 2 different registration approaches and are considering options in both clinical settings.

Okay. And then just some -- kind of a broader consideration. There was a lot of data, as Chris mentioned, about a number of studies with regard to entinostat. Looking at the tumor microenvironment and their combination with entinostat with 214 was mentioned and then an IL-15 antagonist and other molecules. Is the company -- is Syndax prepared to prosecute breast cancer as an indication and as a path forward as well as all the PD-1 combinations in addition to some of these additional novel combinations? Or are those just something we may have to wait and see on or for other people to do? Or how should we think about the other activity and the intriguing activity you've shown in some of the AACR work?

Yes. Thanks for the question, Bert. So obviously, as Rick went through our current financial situation and what we're funded to be able to continue to do, that, of course, includes the Phase III breast cancer trial and includes the ENCORE program, as we've described it to you. As I said in my comments, as we go through the whole proof-of-concept program, we'll make decisions about which of those things we -- if we see signal in multiple tumor types, we may decide to move forward with one and not others, just depends on sort of the unmet need, the clinical -- the sort of competitive environment and where we think we can get the best return. In terms of additional combination work, they're -- as you noted, there were a number of presentations using entinostat in combination with a number of agents. And we actually had many conversations with people who wanted to test entinostat in combination with other agents. I think our view at this point is the data with NKTR-214 was, in our view, particularly exciting. And as we said, we already have a collaboration with them preclinically, so we're continuing that conversation. Some of the other agents where people have expressed interest in combining with entinostat, I think, for now, we'll keep those on the back burner, while we finish out the work that we're doing. But I think that's sort of where we are.

Okay. Just one more quick one then. The Menin-MLL-r inhibitor program, any way to step on the accelerator with that intriguing program as well?

Great question, which I ask the team every week. So we're doing everything we can to move as quickly as we can. But right now, the team is comfortable that they can get the IND filed in the first quarter. But I asked the same question you just asked, and we'll see if they can speed things up a little bit.

Next question comes from Madhu Kumar from B. Riley FBR.

So kind of following on for thinking about the melanoma registration strategy. How do you think about the kind of broader landscape of post-PD-1 drug as a decision calculus for whether you go strictly post-PD-1 in melanoma or post-PD-1 and CTLA-4?

Yes. Madhu, thanks very much for the question. So it is -- again, you guys probably follow this just as detailed as we do. There's a number of molecules that are being developed in melanoma. It's a fairly busy area. I think patients who have failed both the PD-1 and the CTLA-4, as I said, is probably the clearest unmet need because they really only have chemo as an option. The ones who have failed only a PD-1 there is at least the option of giving them ipi. So we keep -- try to keep track of as many of the competitors as we can. We do tend to think of them in sort of 2 different buckets. There is the buckets of what I guess we would call systemic therapies, either antibodies or small molecules, and the bucket of things that are intratumoral therapies. And we separate them simply because we believe that the systemic and oral therapies are probably just a little bit easier go-to-market strategy. The intratumoral is just a little more difficult to make sure that you have people trained who can inject the lesion. And so we keep track of both of those. And there is data accumulating in both spaces, both with oncolytic viruses, with TLR agonists, LAG3, others. So it's an interesting space, but I think the failed both PD-1 and CTLA-4 probably is in more need, and the evidentiary standards may be a little bit lower from a regulatory point of view than for those who only failed the PD-1.

So to that end, what fraction of the patients in the Phase II have failed both PD-1 and CTLA-4 in the fully enrolled population?

Yes. I don't think we've revealed that data yet for the fully enrolled population. For the data presented last year, it was about 2/3 had gotten both.

The next question comes from Christopher Marai from Nomura.

First, just with respect to the colorectal cancer trial changed, sort of what drove that? I know there's high unmet need. You were certainly bullish about the potential responses. Should we read into this that you may see sort of more responses than you had initially anticipated and you kind of have just expanded this due to that potential success and ability to enroll patients? And now we just have a better data set look at? Or had some initial responses kind of have been observed and then sort of not replicated as the trial progressed? And then secondarily, with respect to this readout and some of the others for entinostat in I/O coming up, particularly at ASCO, help us understand some of the biomarkers that might help overlay our understanding of the drug and its activity.

Thanks, Chris. So for colorectal, again, just to be very clear, the main reason for in expanding the enrollment was really around the statistical design of being able to assess the 15% response rate. So in the original design, you had an hypothesize 25% and a lower bound, if you will, of 10%, which means if you saw a 9% or 10% response rate you might not even progress to the second stage of the trial. And as we talked to more colorectal cancer physicians and our collaborators at Merck, we all agreed that, that would -- probably doesn't make a lot of sense. So let's change the specifics around the design and make sure that if you had 10% at your first stage you would still continue because you're in the ballpark of being able to hit that 15%. So it was really around the statistical design and being able to adequately assess even a 15% response rate. The large sample size also does give us more patients potentially to look at biomarkers. So that goes to your second question about the biomarkers. It is, as I pointed out previously, a very comprehensive program. So there's assays looking at the tumor itself. So PD-L1 expression, tumor mutational burden, a variety of different immune cell subsets. As you know, in colorectal cancer, there have been the description of various subtypes, if you will, of colorectal cancer. So we're trying to get our hands around that. And also, we look at a variety of immune cell types in the peripheral blood. So it's a fairly comprehensive review. It does take a little bit of work to sort of dig through all of that. As I noted in my comments, I think in non-small cell lung cancer one of the markers that we have been interested in it does seem promising, and we'll -- you'll be able to see that data at ASCO. But it does take a little bit of time to make your way through all these various assays, collect the data, do the correlative analysis, see if it actually predicts in an independent model outcome. So it's a lot of work, but to be honest, I think it's really quite important. I think we've seen now in the I/O field that at least some companies have gone forward with very broad programs, and they haven't worked out. And others have tried to focus on specific subpopulations, and those may have worked out better. So we really do think it's important if we can to find a biomarker-defined population.

Okay. That's helpful. So it's more of an approach to the biomarker-defined population rather than a unifying sort of view on entinostat's mechanism, although I suppose they kind of intersect.

They do -- let me just get into -- they do intersect. And obviously, if there was a biomarker that was predictive of clinical benefit across various tumor types -- so if it was sort of a unifying biomarker, that, obviously, would be an easier thing from a development point of view. It's just a little bit early to be able to make that conclusion, of course, because we're still waiting for data from 4 of the other tumor types that we haven't read out yet.

Okay. That's helpful. And then in terms of more of the biomarker data, is that sort of a SITC type more presentation in terms of some of the more conclusive biomarker data set? And I have got one last quick one.

So I think -- again, just a set explanation, I think -- as I noted, it's a fairly comprehensive look at biomarkers, so it will be an evolving story over time. I'm not sure I can say exactly when the story -- as you do these analyses, something looks promising, and we can follow up on it. In other cases, you have to do more work until you find something. So it's a little bit hard to gauge a time line for when the biomarker work will advance to a point where we can then use it in subsequent trials.

Okay. Great. And then just to follow up on more of a common theme here. We've seen about a year ago now an indication that entinostat might be helpful in overcoming resistance or nonresponse to PARP inhibitors. I know you had mentioned you have an ongoing discussion with respect to the -- to some other I/O agents. So I'm just wondering, anything on the PARP side of the equation there?

I would say there's nothing imminent on the PARP side.

The next question comes from Tony Butler from Guggenheim Securities.

I want to ask about 602 and triple negative if possible. Would you please remind us -- I think there has been some data with pembro in triple negatives. I think the response rate was something around 20%. I could be wrong there. If you remember that, I would appreciate that. And the other comment is that there have been other data in combination, pembro plus a PARP inhibitor. And I guess the notion here is what would be a good level of activity you would like to see or predict to see with TECENTRIQ, because I'm trying to understand what TECENTRIQ has been able to show as monotherapy in TNBC. And then what would be good with entinostat on top, if that makes sense?

Yes. Thanks a lot, Tony. So I think a number of companies have reported monotherapy, whether over the PD-1 or a PD-L1 in triple-negative breast cancer. And my recollection is the response rate is somewhere in the high teens. I don't recall it being dramatically different from one agent to another. I would just say the way the trial -- the way 602 is set up, the statistical approach is around PFS, and it's powered for hazard ratio of 0.7%. So we'll obviously look at response rate, durability of response, PFS, other end points, but the statistical sign is really based around PFS. I think, again, from a response rate point of view, I think in general we're looking for -- this is in a population of patients who are naive to a PD-1 antagonist. So remember, if you were going to use response rate, you'd be looking for some sort of material improvement in that. I think if you're looking at PFS with a hazard ratio of 0.7% or so, I think, that would be notable. But again, it's -- I'll emphasize that both 602 and 603, all of these are really what we consider proof-of-concept trials, early signs of efficacy. And then you can dig into the data and see what you want to do going forward.

And just briefly, the last question, again on 602. Slight delay, had enrollment been dragging a little bit as you anticipated it earlier than simply by the end of Q2 that really has pushed into early part of '19?

Yes. So we had anticipated 602 would read out top line data at the end of the year. The final enrollment has lagged just a tad. We still think we're going to hit it in the second quarter. But as we look at that, we thought it was prudent to indicate that it's more likely that we'll get top line data the first half of the next year.

The next question comes from Hartaj Singh from Oppenheimer.

This is Emma on for Hartaj. On E2112, if the final PFS analysis readout is negative next quarter, would you also then simultaneously disclose the results of the OS futility analyses to date? And then just to clarify that you would then continue to conduct a futility analysis at each interim for OS at 6-month intervals?

Right. Thanks for your question, Emma. So as you have correctly recalled, if PFS is negative then when the DSMB meets they do both a futility analysis for OS and a positive analysis for OS. So if PFS is negative and we communicate that PFS is negative, that would by inference mean that the futility analysis previously conducted we'd then know that there probably were futility analysis, and they were also -- the trial was not futile. So we wouldn't be able to tell you what the estimated hazard ratios were at that -- at those various analyses. That's not communicated to us by the DSMB, but one could by inference figure, well, PFS was negative, so they were doing futility analyses, and those have all been -- they would have been negative to that time.

Right. Great. And then I believe last quarter you'd indicated that approximately 10% of the OS events had occurred at that first interim, so that negative analysis sounds surprising. Is the second analysis still minus those expectations?

So second analysis with the -- the DSMB communicated to us that the trial will continue as designed, but they did not give us an update on event rate. So I'm not sure we can communicate that to you.

I would now like to turn the call back to Dr. Morrison for further remarks.

Great. Thanks, again, everybody for your interest, and we look forward to seeing all of you in Chicago.

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