Good day, ladies and gentlemen, and welcome to the Syndax first quarter 2018 earnings conference call. At this time, all participants are on a listen-only mode. Later, we will conduct a question and answer session, and instructions will be given at that time. If anyone should require operator assistance, please press the star, the zero, then the one on your touchtone telephone. 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 Shea, 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 would ask you to please turn to our forward-looking statements on slide two.
Before we begin, I would like to remind you that any statement 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 8th, 2018, only. A replay of this call will be available on the company's website at syndax.com. With that, please turn to slide three, 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 three briefly summarizes our corporate strategy, which includes developing three potential best-in-class molecules, entinostat, SNDX-6352, and our Menin-MLL portfolio, which are being tested at five ongoing clinical trials across six 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 four 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 received breakthrough therapy designation from the FDA, as well as our exciting ENCORE clinical trial program, which combines entinostat with PD-1 antagonists. Slide five 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. We now turn to slide six and give you an update on E2112, our phase III trial of entinostat in hormone receptor-positive, HER2-negative breast cancer. Slide six summarizes the trial design and endpoints. We've also summarized 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 this final enrollment progresses.
Once enrollment is completed, we will learn of the results of the final PFS analysis, and if positive, we are 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. 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 six 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 communicate top-line results and present full results at an appropriate medical meeting. We remain confident in the potential outcome of E2112, given that it is based upon strong phase II data, which led to FDA breakthrough therapy designation. Slide seven 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, thus we will have a highly relevant data set in this population. Importantly, as shown on slide seven, we have tested entinostat in three distinct pre-clinical 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 pre-clinical 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 eight makes this 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 nine, 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. 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 for 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've now conducted our regulatory consultations and a number of advisory boards with physician experts in the treatment of melanoma, we'll be providing details on our registration strategy sometime later this quarter. Slide 11 is a summary of where we are with our 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 can 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 16th. It's important to note that these abstracts were submitted in early February with a data cutoff as of late January.
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 two 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. 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 Merck's 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. Data would suggest that the KEYNOTE-189 regimen will increasingly be used in the first-line setting. One should note, 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's a large and growing unmet need in this population of patients for improved therapies. 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 two-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 predicted response rate of 25% for the overall cohort. As we noted on 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. We've therefore modified the SIMON two-stage design to test for a predicted response rate of 15%.
We will enroll a total of 37 patients in stage 1, and if we see at least 3 responses, we'll proceed to stage 2, 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 2 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. Again, we're very pleased with the breadth of our ENCORE clinical programs 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 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.
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 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 PDX models as well as in NPM1 mutant PDX models, 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 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, 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, we look forward to seeing many of you there in Chicago. With that, I'll turn it over to Rick for the financial update.
Thank you, Briggs. Turning to slide 20, for the three months ended March 31, 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 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, 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. Looking ahead, we expect R&D expenses to be $15 million-$18 million for the second quarter and $62 million-$70 million for the full year. Total operating expenses are expected to be $20 million-$23 million for Q2 and $82 million-$90 million for the full year 2018. I'd now like to turn the call back to Briggs.
Thanks very much, Rick. 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, 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 it up to call for questions.
Thank you, ladies and gentlemen. If you have a question at this time, please press the star, then the 1 key on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. One moment for questions. The first question is going to come from Chris Shibutani from Cowen.
Dave, many different clinical trial updates coming for you, especially at ASCO. We just are coming off the heels of AACR as well. There was 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 in which we're thinking about what kind of structure we might be able to see you continue to develop that work, how that might play out? Thanks.
Hi, Chris. Thanks very much for your question. Yeah. What we presented at AACR was a preclinical combination work done with NKTR-214 and entinostat, and I think quite interesting combination therapy. We set up that collaboration with Nektar some time 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. 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.
Thank you very much for taking my question. 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?
Yeah. Thanks, David, for your question. 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 trials. 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. 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 a PD-1. We think that's the growing area of unmet need.
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. Thanks for that. 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. 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 little lower response rate, given how important it is to find new agents in this area. Compared to some of the other agents that are used in this area, they thought even 15% would be of interest. I noted on our last call that it's an open label trial, and we have seen activity.
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." That was the reason to expand the colorectal population and to change the thresholds for the study.
Thank you for taking my questions.
The next question comes from Konstantinos Aprilakis from JMP Securities.
Hi, good afternoon. This is Simon Gruber on for Constantine. Just a real quick question. The E2112 PFS data coming in Q3. I'm just wondering if there's any accompanying data that we can expect or if it'll just be like a top-line PFS number.
Right. Simon, thanks for the question. At the time that the data's 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.
Okay, great. Thank you.
Next question comes from Bert Hazlett from BTIG.
Thank you. 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.
Yeah, sure, Bert. I think as we may have talked about previously, there's essentially, we think of it as two different populations of patients. There are patients today who are being treated with a PD-1 antagonist as a monotherapy and their first therapy, then subsequently may receive a CTLA-4 ipilimumab. There are other patients who are treated with both agents right up front. At the end of the treatment regimen, essentially, you end up with a cadre of patients who receive both a 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, if they're still suited, 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 will want to know how does the agent compare to treating them with Ipi, for example. We think of those as two different registration approaches and are considering options in both clinical settings.
Okay, thank you. 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 two and four, as was mentioned, and then IL-15 antagonist and other molecules. 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? 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 that you've shown in some of the AACR work?
Yeah. Thanks for the question, Bert. 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, if we see signal in multiple tumor types, we may decide to move forward with one and not others, just depends on the unmet need, the competitive environment, and where we think we can get the best return.
In terms of additional combination work, 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 pre-clinically, 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. I think that's sort of where we are.
Okay, just one more quick one. The Menin-MLL inhibitor program. Any way to step on the accelerator with that intriguing program as well?
Great question, which I ask the team every week. We're doing everything we can to move as quickly as we can. Right now, the team is comfortable that they can get the IND filed in the first quarter. I ask the same question you just asked, and we'll see if they can speed things up a little bit.
Okay. Thank you very much.
Next question comes from Madhu Kumar from B. Riley FBR.
Yeah, guys. Thanks for taking my question. 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 drugs as a decision calculus for whether you go strictly post PD-1 in melanoma or post PD-1 and CTLA-4?
Madhu, thanks very much for the question. It is, again, you guys probably follow this just as detailed as we do. There is a number of molecules that are being developed in melanoma. It is a fairly busy area. I think the patients who have failed both the PD-1 and a 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. We try to keep track of as many of the competitors as we can. We do tend to think of them in two 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 intra-tumoral therapies.
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 intra-tumoral is just a little more difficult to make sure that you have people trained who can inject lesions. We keep track of both of those. There is data accumulating in both spaces, both with oncolytic viruses, with TLR agonists, LAG-3, others. It is 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 have only failed a PD-1.
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?
I don't think we've revealed that data yet for the fully enrolled population. For the data we presented last year, it was about two-thirds had gotten both.
Okay, great. Thanks for taking my question.
The next question comes from Christopher Marai from Nomura.
Hi. Good afternoon, guys. Thanks for taking the questions. First, just with respect to the colorectal cancer trial change, sort of what drove that? I know there's high unmet need. You are certainly bullish about the potential responses. Should we read into this that you may see more responses than you had initially anticipated, and you kind of just expanded this due to that potential success and ability to enroll patients, and now we just have a better data set to look at? Or had some initial responses kind of been observed and then sort of not replicated as the trial progressed? Then secondarily, with respect to this readout and some of the others for entinostat in IO coming up, particularly at ASCO, maybe help us understand some of the biomarkers that might help overlay our understanding of the drug and its activity. Thank you.
For colorectal, again, just to be very clear, the main reason for expanding the enrollment was really around the statistical design of being able to assess the 15% response rate. In the original design, you had a hypothesized 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 stage 2 of the trial. As we talk to more colorectal cancer physicians and our collaborators at Merck, we all agreed that that would probably doesn't make a lot of sense. Let's change the statistics around the design and make sure that if you had 10% at your stage 1, you would still continue because you're in the ballpark of being able to hit that 15%.
It was really around the statistical design and being able to adequately assess even a 15% response rate. The larger sample size also does give us more patients potentially to look at biomarkers. That goes to your second question about the biomarkers. It is, as I pointed out previously, a very comprehensive program. There's assays looking at the tumor itself. 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. We're trying to get our hands around that. Also, we look at a variety of immune cell types in the peripheral blood. 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 you'll be able to see that data at ASCO. 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 outcomes. 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 IO field that at least some companies have gone forward with very broad programs, and they haven't worked out. Others have tried to focus on specific subpopulations, and those may have worked out better. We really do think it's important, if we can, to find a biomarker-defined population.
Okay, that's helpful. It's more of an approach to the biomarker-defined population rather than a unifying sort of view on entinostat's mechanism.
Right
kind of intersect. Okay, then.
They do intersect. Obviously, if there was a biomarker that was predictive of clinical benefit across various tumor types, so that 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 four of the other tumor types that we haven't read out yet.
Okay, that's helpful. In terms of more of the biomarker data, is that sort of a SITC type more presentation in terms just of a more conclusive biomarker data set? I've got one last quick one.
I think, again, just to set expectations, I think, as noted, it's a fairly comprehensive look at biomarkers, it'll be an evolving story over time. I'm not sure I can say exactly when. 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. It's a little bit hard to gauge a timeline for when the biomarker work will advance to a point where we can then use it in subsequent trials.
Okay, great. Just to follow up on one of the common themes here. We've seen about a year ago now an indication that entinostat might be helpful in overcoming resistance or non-response to PARP inhibitors. You'd mentioned you have an ongoing discussion with respect to some other IO agents. I'm just wondering, anything on the PARP side of the equation there? Thank you.
I would say there's nothing imminent on the PARP side.
Great. Thanks.
The next question comes from Tony Butler from Guggenheim Securities.
Thanks very much, Briggs. I want to ask about 602 and triple negatives, if possible. Would you please remind us, I think there has been some data with pembrolizumab 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. The other comment is that there have been other data in combination pembrolizumab plus a PARP inhibitor. 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. Thanks.
Thanks a lot, Tony. I think a number of companies have reported monotherapy, whether it was a 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 trial 602 is set up, the statistical approach is around PFS, and it's powered for a hazard ratio of 0.7. We'll obviously look at response rate, durability of response, PFS, other endpoints, but the statistical design is really based around PFS. Again, from a response rate point of view, in general, this is in a population of patients who are naive to a PD-1 antagonist. If you were going to use response rate, you'd be looking for some sort of material improvement in that.
If you're looking at PFS with a hazard ratio of 0.7 or so, that would be notable. Again, I'll emphasize that both 602 and 603, all of these are really what we consider proof-of-concept trials, early signs of efficacy, then you can dig into the data and see what you want to do going forward.
Thanks. Just briefly, the last question, again on 602, slight delay. Had enrollment been dragging a little bit? Had you anticipated it earlier than simply by the end of Q2 that really is pushed into early part of 2019? Thanks.
We had anticipated that 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, 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 next year.
Thanks, Briggs.
The next question comes from Hartaj Singh from Oppenheimer.
Hi, this is Emma on for Hartaj. On E2112, if the final PFS analysis readout is negative next quarter, would you also simultaneously disclose the results of the OS futility analyses to date? Just to clarify that you would continue to conduct a futility analysis at each interim for OS at six-month intervals.
Right. Thanks for your question, Emma. As you have correctly recalled, if PFS is negative, when the DSMB meets, they do both a futility analysis for OS and a positive analysis for OS. If PFS is negative and we communicate that PFS is negative, that would by inference mean that the futility analyses previously conducted, we would know that there probably were futility analysis, and also that the trial was not futile. We wouldn't be able to tell you what the estimated hazard ratios were at those various analyses. That's not communicated to us by the DSMB. One could, by inference, figure, well, PFS was negative, so they were doing futility analyses, and those have all been a negative to that time.
Right. Great. I believe last quarter you'd indicated that approximately 10% of the OS events had occurred at that first interim. That negative analysis is unsurprising. Is the second analysis still in line with those expectations?
The second analysis, the DSMB communicated to us that the trial will continue as designed. They did not give us an update on event rates. I'm not sure we can communicate that to you.
Great. Thank you.
I would now like to turn the call back to Dr. Morrison for further remarks.
Great. Thanks again, everybody, for your interest. We look forward to seeing all of you in Chicago.
Ladies and gentlemen, thank you for participating