Good day, everyone, and welcome to the Syndax call. Today's call is being recorded. At this time, I would like to turn the call over to Megan Myers of Argo Partners. Please go ahead.
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 clinical development plans for the combination of entinostat and KEYTRUDA in non small cell lung cancer. I'm Megan Myers with Argo Partners. And with me this afternoon are Doctor. Briggs Morrison, Chief Executive Officer Michael Myers, Chief Medical Officer and Doctor.
Martin Edelman, Department Chair Hematology, Oncology, Fox Chase Cancer Center. Also joining us on the call today for the question and answer session is Michael Metzger, President and Chief Operating Officer Doctor. Peter Orlentlich, Chief Scientific Officer and Rick Shea, Chief Financial Officer. This call is being accompanied by a slide deck that is available on the webcast. I would like to first turn to our forward looking statement on Slide 2.
Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward looking statements 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 in the company's most recent quarterly report on Form 10 Q as well as any other reports filed with the SEC. Any forward looking statements represent our views as of today, October 25, 2018 only. A replay of this call will be available on the company's website, www.syndex.com, following this call. With that, please turn to Slide 3, and I'm pleased to turn the call over to Doctor.
Briggs Morrison, Chief Executive Officer of Syndax.
Thanks very much, Megan, and thank you to everyone for joining us on today's call at short notice. We're excited about the agenda for today's call, which is shown on Slide 3. After I make a few introductory comments, Doctor. Michael Myers, our Chief Medical Officer, will walk through the data from the PD-one refractory non small cell lung cancer cohort of ENCORE-six zero one that we recently presented at the World Conference on Lung Cancer. And we'll also walk through the study design of ENCORE 607, our proposed registration trial in non small cell lung cancer.
Doctor. Martin Adelman from Fox Chase Cancer Center was the scheduled discussant at the conference, and we are very fortunate to have Doctor. Adelman joining us today to provide his perspective on the emerging standard of care in non small cell lung cancer, giving the presentation he was scheduled to give at the World Conference on Lung Cancer. Will then take questions on the lung cancer data, the ENCORE 607 trial design and Doctor. Adelman's presentation, noting that Doctor.
Adelman is not available for the entire duration of the call. I will then provide a brief commentary on the PFS results that we announced for the E2112 study and then reopen the call to any further questions. Slide 4 provides a summary of the milestones communicated on our last call in August of this year. We indicated at that time that we would provide updates on E2112, our Phase III breast cancer trial in patients with hormone receptor positive HER2 negative breast cancer as well as non small cell lung cancer and melanoma during the Q4 of this year. We have just announced that E2112 has completed enrollment of 605 patients, that the PFS result did not meet the high bar for statistical significance and that the E2112 trial will continue as planned beyond the recently completed 3rd interim analysis of OS with continued interim planned analyses conducted approximately every 6 months.
I'll provide additional commentary on E2112 later in the call. After returning from the World Conference on Lung Cancer and speaking with a number of lung cancer experts as well as monitoring the data presented at ESMO quite recently, we are eager to share with you today the update on our plan for entinostat in non small cell lung cancer. Slide 5 summarizes our ENCORE clinical trial program, which we are testing entinostat in combination with PD-one pathway antagonists. We've previously communicated that 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. Taking those factors into account, we are pleased to announce today that we are moving forward with a registration trial in non small cell lung cancer patients whose disease has progressed after both platinum based combination chemotherapy and a PD-one antagonist therapy, an area of clear unmet medical need.
Before Doctor. Myers provides more details on this non small cell lung cancer registration trial, let me call out 2 key points. The trial is designed to both validate the classical monocyte biomarker and to demonstrate that the combination therapy of entinostat plus KEYTRUDA is superior to standard of care chemotherapy in the high monocyte population of patients. The trial will enroll approximately 200 patients with data potentially available within 2 years, the second half of twenty twenty. This could position us to be the 1st novel therapy with regulatory approval both in the U.
S. And the EU in the sizable population of lung cancer patients. This would also potentially be our 2nd launch indication for entinostat, following closely on the heels of breast cancer, thus enabling the build out of a very significant franchise. Let me now turn things over to Doctor. Michael Myers, our Chief Medical Officer, to review the ENCORE-six zero one data that was presented by Doctor.
Matt Hellman at the World Lung Conference last month. Michael?
Thank you, Briggs. Slide 6 provides a summary of the ENCORE-six zero one KEYNOTE-one hundred and forty two study design. Today, I will review the Phase 2 data from patients with non small cell lung cancer whose disease had progressed on a PD-one pathway antagonist. These data were presented recently at the World Conference on Lung Cancer as shown on Slide 7. Slide 8 shows the demographics of the 76 patients enrolled in this cohort.
All patients had previously received both chemotherapy and a PD-one antagonist. For about 2 thirds of the patients, their last therapy before entering ENCORE-six zero one was
a PD-one
antagonist and the median time since last therapy was a little over 2 months. Most of the patients had not experienced an objective response to their prior PD-one therapy. And consistent with this clinical observation, the majority of patients had either less than 1% or 1% to 49% expression of PD L1 at the time of study entry onto ELLENCOR-six zero one using the validated Merck assay. Slide 9 shows a waterfall plot for this cohort. The objective response rate for the entire study population was 10% with a 95% confidence interval of 4% to 19%.
The median PFS in the overall population was 2.8 months. On Slide 10, we show the spider plot for the full cohort, which highlights that the median duration of response was 5.3 months and that there were a large number of patients with prolonged stable disease in addition to the patients with objective responses. On Slide 11, we show more detail on the responding patients. You can see that most of the responders went on to our trial after progression on a PD-one antagonist and most were PD L1 negative. On Slide 11, we show the safety profile of the combination.
In general, the regimen was tolerated well with a manageable adverse event profile. 14% of patients discontinued therapy due to a treatment related adverse event. We have previously identified a biomarker that may predict clinical benefit and Slide 13 highlights a recent paper that identified classical monocytes, a sample from peripheral blood as a strong predictor of both PFS and OS in patients with melanoma who were treated with a PD-one antagonist. Based upon this paper and the well described effect of entinostat on the monocyte lineage, we analyze whether this same biomarker would predict clinical benefit in the 76 lung cancer patients we have just reviewed. Slide 14 shows the swimmer's lane plot coded by baseline levels of circulating monocytes.
So the patients with the high monocytes are in green and the patients with low monocytes are in the reddish color. As you can see, the majority of patients who experienced an objective response were monocyte high patients. And notably, the monocyte high patients also appeared to have experienced a significant increase in response to duration as well. Indeed, on Slide 15, we show that both PFS and objective response rate are significantly improved in the population of patients with high peripheral blood classical monocytes. The PFS of about 5.3 months that we observed in the high monocyte population is roughly double of the PFS that has been reported in the literature in patients treated with standard of care chemotherapy in this setting.
We have reviewed these data with physicians who are expert in the treatment of non small cell lung cancer and in the development of novel agents for this disease. They uniformly found the data highly interesting and encouraged us to pursue further the development of entinostat in non small cell lung cancer, especially in the high monocyte population. Slide 16 shows the treatment options most commonly used to treat patients with metastatic non small cell lung cancer. As you are aware, it is common practice to use selection markers such as EGFR, ALK, PD L1 expression and tumor mutational burden to identify non small cell lung cancer patients who are more likely to respond to various treatments. We anticipate approximately 30% of patients whose disease has progressed on anti PD-one treatment would have high baseline peripheral bonocytes as according to our assay.
And this would represent a large market opportunity for our combination of entinostat and pembrolizumab. Slide 17 shows the registration trial we designed for the entinostatpembrolizumab combination. Based on those comp discussions with non small cell lung cancer experts as well as input from the FDA. To be eligible for the study, patients must have received a platinum based chemotherapy and pembrolizumab. We anticipate that most patients will have received the triplet of pembrolizumab, pemetrexed and cisplatin, the regimen used in the KEYNOTE-one hundred and eighty nine study and will it progress while on maintenance pembrolizumab.
Patients will also be included if they have received platinum based chemotherapy as first line treatment followed by pembrolizumab. We will first assess the percent of baseline classical monocytes in peripheral blood using a validated assay. Those patients with low monocytes will be treated with entinostat plus pembrolizumab. Those with high monocytes will be randomized to be treated with standard of care chemotherapy as per investigators' choice versus the entinostatpembrolizumab combination. The primary endpoint of this study is PFS based upon the impressive PFS data we saw in Phase II.
The statistical approach will be to first test arm A entinostatpembrolizumab in patients with high monocytes versus arm C entinostatpembrolizumab in patients with low monocytes to validate the monocyte biomarker. The second statistical analysis will be armantinostat plus pembrolizumab in patients with high monocytes versus armb standard of care chemotherapy in the same patients with high monocytes. The secondary endpoints will include objective all of which are important in improving the efficacy and benefit of this regimen. The trial will have limited power to assess an OS benefit. We recognize that.
However, we do think that PFS serves as a basis for full approval in the United States and at least conditional approval in the EU. As you can see, the total number of patients is approximately 200. We anticipate completing the trial and having top line data both validating the biomarker for patient selection and proving the efficacy of entinostat and pembrolizumab in the second half of twenty twenty. I will now turn the call over to Doctor. Edelman, who will discuss the significance of these results.
Doctor. Edelman?
Thank you. So what I'm going to in my slide, my first slide, demonstrates the molecular subsets of lung cancer and how much the field has fragmented in the last few years. Within that slide, I also demonstrate some of the fact that even within subsets, as for example, with Rett, there are subsets and subsets. So this has become an increasingly fragmented field. And on my next slide, one can see that, which compares electro slide that I had from 2,005 with something from last year, which is already obsolete that there's been an increasing number of options in non small cell lung cancer.
So while this is unquestionably great news for patients and they're treating physicians, it has created a number of problems in developing trials as the patient eligibility for every trial requires a variety of criteria, which were very different from what we had as recently as 10 or 15 years ago. In the next slide, I give an example of the current. This is pretty much presented, some fully published at this point, demonstrate that the use of immunotherapy in high PD L1 patients is superior to standard chemotherapy. However, as can be seen, the overwhelming majority of patients will progress within approximately a year or less than that. And therefore, there still is a substantial unmet need.
Very few patients will have persistent efficacy beyond 30 months. So therefore, even with the progress with immunotherapy, probably fewer than 3% to 5% of patients are actually durable long term responders. Similarly, for chemotherapy versus chemoimmunotherapy, the next slide demonstrates that even in this situation, the overwhelming majority of patients will progress, again, with very few long term survivors. If you'll turn your attention on that slide to the first two trials, the KEYNOTE-twenty one cohort G and KEYNOTE-one hundred and eighty nine, what I'm demonstrating in that is if you look at the control arms, the overall survivals drop in the Phase II from 20 months 11 months and are there to simply indicate that between Phase II and Phase III, there could be considerable variability as one goes to larger studies. So all early results need to be viewed with some caution.
So what are the unmet needs? My next slide in advanced non small cell lung cancer. The benefits of immunotherapy alone or in combination are real but limited regardless of what PD L1 or tumor mutation burden or any current biomarker would have. We have very few patients who are truly long term survivors, I. E, beyond 36 months.
And the problem right now is we have several populations of patients and no clear definitions. There are those who are primarily resistant to the use of immunotherapeutics. There are those who develop resistance to therapeutics. And furthermore, there are those who relapse after receiving immunotherapy as part of the adjuvant treatment in stage 3 and what will likely develop an earlier stage of disease. If one looks at the curves there, this is from the KEYNOTE-one hundred and eighty nine study presented by Doctor.
Gandhi. And you can see from the green arrow there that there's a long way down from 100% to even the plateau in progression free survival at approximately 18 months. So again, a clear unmet need in advanced non small cell lung cancer. My next slide, there are many potential targets and many trials that address these. But we have a number of issues in the next generation of studies.
We need clear rationale, and these days, it's become a little bit like what we had many years ago with carboplatinimintaxol, where whatever your drug was, was added into that, but we need clear evidence of mechanistic and preclinical synergy. And then there are questions of how to combine the drugs, whether they should be additive, sequential or phased and the specific population, whether naive, resistant, refractory and whether there's intervening therapy. And again, there are no formal universally accepted definitions for the resistant and refractory settings at this time. So what do we need to know on what is promising? Well, in any situation and at the time of the World Conference, I was addressing several studies.
We need to look at the prior lines of therapy. For the for tinnostat, there was prior immunotherapy as well as chemotherapy in many cases. And we need to know what their activity was in specific context of TMB and PD L1 and what should the endpoints be in early studies because, again, this will depend very much on what their prior therapy and response was as well as the specific molecular and other characteristics. So it's really unclear what should be considered as evidence of promise, whether it's response rate, progression free or landmark survivals. It will be nice to have biomarkers for selection based upon good hypothesis or exploratory in the population.
There are many practical issues of fragmentation of the population, too many questions in too many trials right now and a rapidly changing landscape where trials are frequently becoming obsolete even before activation. And how do we distinguish a trial to refer a patient in a competitive landscape. And so therefore, a robust, easily obtainable biomarker is a definite plus and simplified on study requirements. Most studies these days are requiring a substantial tissue and other requirements. So if one turns to the specific entinostat and pembrolizumab study, this was a Phase II single arm trial, but a substantial number of patients were actually resistant to refractory to the anti PD-one and PD L1 agents, and many were treated and even some demonstrated response immediately after progression with the anti PD-one or PD L1 agent.
The monocyte high status appears to select for patients who obtain durable benefit. 7 of 8 with of the 8 patients who had 36 weeks or more of benefit were monocyte high, while 46 to 47 with low monocytes did not benefit. However, there were 12 of 19 with high monocytes did not benefit. So the marker is not perfect. It does seem to be necessary, but not necessarily sufficient.
However, the test does have a good sensitivity, by my calculation, about 88% and is very specific, 98%. But the numbers are small with wide confidence intervals. So in the planned approach, it will allow for some better assessments of this biomarker. And this appears to be a very reasonable approach to enriching the population and enhancing the opportunity for success with while minimizing the use of patient resources. Thank you.
And Doctor. Myers. So operator, we'd like to now open the line for any questions people have about Doctor. Meyer's presentation or Doctor. Elliman's presentation on non small cell lung cancer.
So any questions for those 2 speakers only, we'll talk more about 2,112 after.
Thank you. And our first question comes from David Lebowitz with Morgan Stanley. Your line is open.
Thank you very much for taking the question. In this in the low monocyte and high monocyte populations just in typical patients at this stage, what's is there any breakdown of what the expected survival or how quickly it will take under a normal treatment for these patients to progress? I guess trying to create some sort of a baseline for how to look at these patients going forward?
Right. So maybe I'll take that question, David. Thanks very much. So I think there is data some data in the literature on the outcome of patients in this population treated with standard chemotherapy. There's not data in the literature on how that breaks out by high or low monocytes.
Okay. So we don't really have a baseline to compare how these patients
might
do respectively on a I guess on a purely controlled basis, high monocyte versus low monocyte?
Yes, that's right.
David, I would add though that high monocytes are classically considered to be a poor prognostic factor, which I think makes our data even more compelling.
Sure. Okay. Thanks for taking the question.
Thank you. And our next question comes from Chris Shibutani with Cowen. Your line is open. Great.
Thank you very much. Doctor. Edelman, I was curious to know your thoughts given the reference that you highlight where the peripheral classical monocyte is identified as a predictor of clinical response to PD-1s, What would you expect upon PD-one rechallenge in these high and low monocyte populations? I think one of the questions becomes what will the incremental benefit be for the combination with entinostat? So specifically then, what would you expect from a PD-one rechallenge?
So there are 2 different things here. The paper was in melanoma and that had high monocytes as a predictive marker for the benefit from anti PD-one therapy. In the trial that was presented by Doctor. Hellman, monocytes were assessed. And so this was a group where the patients did have high monocytes, and that's what was the predictive marker.
And those patients had already, for the most part, progressed after an anti PD-one or PD L1 agent. So in this particular setting in lung cancer, that's where the marker was utilized and what had the predictive benefit.
And I think, Chris, it's important to note that the majority of patients had received PD-one as their immediate prior therapy and that the median time to coming on to our trial was only about 2.2 months. So that it was almost as if entinostat was being added to a PD-one antagonist in the setting of progression. And so strictly speaking, it was not a rechallenge effect.
Our next question comes from Robert Hazlett with BTIG. Your line is open.
This is actually Jake Colby on the line for Bert. Thanks for the question. I guess I wanted to follow-up with a comment that ESMO reinforced your belief in the Intenostat KEYTRUDA combination. Could you just provide a little bit more detail around that? And then I guess secondly, I was wondering if you could provide any more details on the powering assumptions for PFS library endpoint?
Thanks.
Sure. So I wouldn't say that ESMO reinforced our it changed our conviction around entinostat as a potential therapy for these patients. I think what we heard from ESMO is what other competition is there. So I think in my prepared remarks, I noted that our decision tree at which projects to take into registration trials depends on unmet need, depends on the competitive landscape and depends on our ability to give a return to it on our investment. And we think ESMO didn't there wasn't really anything at ESMO that made us feel like from a competitive point of view, we weren't in a really good position.
In terms of the powering of the trial, I don't think we've said we were not really at liberty to say just yet about, what the trial powered for. We'll do that in subsequent conversations.
Thank you.
Thank you. Our next question comes from Madhu Kumai from B. Riley FBR. Your line is open.
Hey guys, thanks for taking my question. So a question for Doctor. Edelman. In your experience, is there a material difference between patients who respond to a PD-one containing therapy and then progress versus patients who just kind of blow through the PD-one therapy with no immediate response?
Well, therefore, in addressing this, it's essentially my personal clinic and it's anecdotal. But certainly, the patients and there's also the people who had chemoimmunotherapy, which is where the fields moved to versus those who received immunotherapy as their second line in the past. And so these are all evolving and changing populations. But the patients who had gotten, say, immunotherapy in second line for the year or 2 where that was the big standard and the only place you could use it outside of a trial, patients who blew right through immunotherapy did not do very well. They progressed very rapidly and usually died very shortly afterwards.
For the patients who have now been getting chemoimmunotherapy and then progress similarly their outcomes are not good. And there's in fact it's been an interesting set of questions of where do you go, which chemotherapeutic should you use, etcetera. There are some patients who if they've had so if they just blow right through whatever their frontline therapy is, they don't do well. And that's historical truth. I mean, it was the same thing with standard chemotherapy in the frontline.
A patient who would progress rapidly through that did not respond well to docetaxel. The people who respond to subsequent therapies are basically the people who had benefit from the prior treatments. So that basic truth has not, for the most part, really changed. For patients who have had some degree of benefit, many of them continue on and that's obviously seen when you have, say, a PFS of 20 months or so and then an OS that's 30 or 40, clearly they've had benefit that comes from other things. There does appear and I tend to believe that this is true is there's probably some subset out there where immunotherapy tends to set them up for benefit from subsequent chemotherapy.
So there is a need for controlled trials in this because we're not really sure what happens in that group. As opposed to the use of cytotoxics, there is there are some persistent effects of the immunotherapeutics even after cessation. Does that address your question?
Yes. And you got to my second question. So then a question for the team. In the study, when you talk about patients who progress on PD-one therapy, does that include patients who respond and then stop responding and patients who never responded to the PD-one therapy? And do you stratify on those groups?
Manu, just to clarify the question, do you mean for the next trial, ENCORE 607?
Yes, sir.
Yes. So again, we suspect, as Doctor. Adelman pointed out, that the field has pretty much moved to sort of chemoimmunotherapy first line. So the vast majority of patients will probably get chemoimmunotherapy as their initial therapy. So it's a little bit different than and most of those patients will have either as you said, they don't respond at all.
And as Doctor. Edelman said, those patients are not tend not to do well or they've had a response, they're now on their maintenance pembro and then they progress.
Yes. I'm asking for ENCORE 607. Do you include both of those as patients who progress after response PD-one plus chemo and patients who never responded to PD-one plus chemo that kind of progressed through from the jump? You include both, okay.
They're both eligible, right.
And do you stratify on those situations?
We haven't disclosed that yet.
Our next question comes from Joel Beatty with Citi.
Hi, thanks for taking the question. Question on the monocyte biomarker, is this a marker that cancer physicians are familiar looking at and are already making treatment decisions based on or will this be something new for them?
This will be something new for them. However, to Doctor. Edelman's point, this is a very easy assay. It's a simple peripheral blood draw and the monocytes can be counted easily and quickly, so there will be rapid turnaround by a validated laboratory at the time that the trial actually is initiated. And we believe that this would be a strategy that could be easily adopted by the majority of medical oncologists, whether at academic centers or in the community.
Great. And is there a proposed mechanism of action and why patients with high or low monocytes might respond to different therapies?
Yes. So maybe if I could ask Peter Ordentlich on the call. Peter, do you want to give a brief answer to that one?
Yes, certainly. Yes, it's actually quite interesting. We've been doing gene expression work on the tumor biopsies from the patients, both in the high and low groups. And it looks like we've identified gene expression pathways within the tumor that are associated with the monocyte levels and in fact give us insight into the mechanism of how entinostat pembro combination may be working. So it's actually pretty fascinating science.
Hopefully, we can present it shortly.
Great. Thank you.
Thank you. Our next question comes from Ed White with H. C. Wainwright. Your line is open.
Hi, thanks for taking my question. So, Doctor. Edelman had said that the trials right now are becoming obsolete before completion. And we just with the last question, we talked about the monocyte biomarker being new and doctors aren't familiar with it. I just wanted to ask about the enrollment and what you're assuming for enrollment.
How many sites will be used? And are you confident that you're going to be able to complete enrollment in the fashion that you mentioned, getting the second half data in the second half of 'twenty, just what gives you confidence that, that will be the timeframe? Thank you.
So, I don't think we're in a position to disclose the number of sites. Obviously, that is the result of a very intensive feasibility study that will be conducted as we initiate the trial. Suffice it to say that we will be tasked with including as many sites necessary as to be able to complete enrollment of the trial in rapid fashion, so that the results will not in fact be obsolete. I think that's all we're at liberty to say at this point.
Yes. And I think the only thing I would add to Michael's comment is, I think as Doctor. Edelman went through, the field is pretty generally moving to chemoimmunotherapy as first line. So I think these patients who have progressed after chemotherapy, there unfortunately will be large numbers of them available for treatment. And the earlier question about what did we see at ESMO or World Lung in terms of emerging treatment for that population of patients, we actually think that we're probably in the lead there.
So I don't think that that standard of care is going to change during the time that we're enrolling this trial.
Okay. Thank you.
Thank you. And there are no other questions in the queue.
Okay. Well, thanks very much for all the questions. Let me again thank Doctor. Adelman for joining us today. I know he's very busy, and I hope you appreciate his perspective on the potential for entinostat to play a role in this emerging lung cancer treatment landscape.
So now let me provide a brief commentary on E2112. So Slide 29 again summarizes the trial design. The trial has now randomized 605 patients to exemestane versus exemestane atinostat, and there are 2 independent primary endpoints, PFS and OS. We now know that the PFS analysis did not meet the high bar for statistical significance, which would have provided us the earliest regulatory filing opportunity for entinostat in hormone receptor positive breast cancer. We also know that the trial will progress as designed, having recently passed the 3rd interim analysis for OS.
As we've noted before, OS analysis is done approximately every 6 months, and the next interim OS will be around May of 2019. The OS result could therefore be available within 6 months from now or depending on the event rate and the treatment effect may not be available until a subsequent OS analysis. Slide 30 is a reminder of the data that resulted in the FDA granting breakthrough therapy designation to the entinostat exemestan combination for patients with hormone receptor metastatic breast cancer who progressed on treatment with a non steroidal aromatase inhibitor. This slide shows the results for both PFS and OS from the Phase II ENCORE-three zero one trial. The trial was positive for both endpoints with the treatment effect appearing greater for OS than for PFS.
And indeed, it was the OS observation that led to the breakthrough therapy designation. So I'd like to provide some additional perspective on the two primary endpoints of E2112. Slide 31 summarizes this information. It's important to remember that E2112 is primarily an OS trial. The breakthrough therapy designation that we received from the FDA was based upon the impressive OS results seen in our Phase II trial.
The hazard ratio that we observed for OS in Phase II was 0.59. E2112 has 80% power to detect a less impressive hazard ratio of 0.75 and E2112 would be statistically significantly positive at hazard ratio of 0.8. Moreover, the Type 1 error rate for OS is 0.048, which is basically the same as the standard 0.05. We should contrast this to PFS for which we saw a hazard ratio of 0.73 in Phase 2 and yet E2112 was designed to detect a hazard ratio of 0.58 and would have only been statistically significantly positive if the hazard ratio was 0.67 or lower. And perhaps most importantly, the Type 1 error rate for the PFS test was 0.002.
Hence, based upon the Phase 2 data and the design of the trial, OS is considerably more likely to positive than PFS. And indeed, we remain very confident that E2112 will be a positive OS trial. So let me now summarize where Syndax is today. As I noted in my introductory comments, Slide 32 depicts the series of Phase II trials we have undertaken to examine the potential of entinostat to enhance the efficacy of PD-one antagonists. Today, we've described the final Phase II data from the cohort of non small cell lung cancer patients who have progressed on both chemotherapy and a prior PD-one antagonist, and we've described our plans for further development.
The European Society For Medical Oncology was held last week in Munich and we reviewed the relevant clinical data presented at that meeting as well as data from other recent scientific congresses. We remain incredibly enthusiastic about the data we've just reviewed with you and we believe we're actually very well positioned to capitalize on our leadership position in non small cell lung cancer. I want to again repeat the 2 key points I made earlier. As designed, our planned registration trial can both validate the classical monocyte biomarker and demonstrate that the combination therapy of entinostat plus KEYTRUDA is superior to standard of care chemo in the high monocyte population. The trial is very efficiently designed and will enroll approximately 200 patients with data potentially available within 2 years, second half of twenty twenty.
This could position us to be the 1st novel therapy with full regulatory approval both in the U. S. And EU in the sizable population of patients and would be our 2nd significant launch in the next few years following on the heels of a breast cancer approval. As indicated on Slide 33, we also have 2 randomized Phase II trials enrolling approximately 200 patients reading out over the next 6 months, 1 in triple negative breast cancer and 1 in ovarian cancer. Now that enrollment is complete in E2112, we look forward to the OS data with 2 interim OS readouts scheduled for 2019.
And in addition, we remain on track to file the IND for our Menin program in the first half of twenty nineteen. We believe we have numerous programs with which build value for our shareholders. With that, let me open the call to any additional questions that people might have.
We have a question from David Lebowitz with Morgan Stanley. Your line is open.
Thank you very much for taking my question again. With respect to the OS analysis that recently occurred, I'm assuming that there's not only the ability to stop the trial based on efficacy, but what's the threshold I guess, to stop it based on futility?
Michael, you want to take that one?
So David, there clearly are futility analyses at the time of each interim analysis for overall survival, they are driven the boundaries are actually for both disclosed by the ECoG IDMC as to what the number of events is at that time. What I would tell you is from knowing the trial designs that clearly if there were no benefit in terms of overall survival that would have triggered a futility, a positive futility result.
Okay. Thank you for answering that question.
Thank you. And we have a question from Joel Beatty with Citi. Your line is open.
Hi, thanks for taking the question. I see that the trial is 80% empowered to detect an hazard ratio of 0.75 on overall survival. Could you just discuss how to think about that in light of the multiple interim analysis that are occurring? Each interim powered for that? Or is that just the final analysis and then the interims are less?
Yes. So Joel, the overall the way the trial is designed is there's 80% power for the 0.75%. And the minimum hazard ratio that would be specifically significant is 0.8, which would translate based upon the assumptions of the trial to about a 5 month improvement in overall survival. There is a small amount of alpha that is spent at each one of the interim analyses. And again, I don't think the ECOG IDMC has discussed what that small amount of alpha is that's spent, but it's relatively minor.
Okay. Got it. And then can you remind us, what triggers the final OS analysis? And when does that expect to happen?
The final OS analysis is at 4 10 events. And this is, of course, an event driven trial. So we don't know exactly when those 410 events will occur. Based upon modeling that we've done, we think that it's potentially going to those full 410 would probably be the analysis in November of 2019, although it could drift into 2020.
Thank you.
Thank you. Our next question comes from Madhu Kumar with B. Riley FBR.
Yes. Thanks for taking my question. So on that point on kind of model timing for the OS readout, does that account for some fraction of patients having now previously been on CDK4six inhibitor therapies? And this is a difficult question because I know earnings are coming up, but kind of back of the envelope based on your cash runway, thinking about both 2,112 and ENCORE 607, based on what we know the current kind of previously described cash position you guys have, with those trials kind of ramping up and continuing, what is the kind of cash runway for you guys?
Yes. So Madhu, I think the question about the cash runway, we actually will go into that in some detail our next quarterly call, which will be coming up fairly shortly. So we'll pass on that question for now. I think the question of the timing, remember that when the trial started, there were probably a fair number of patients who did not have a CDK4six before they came into the trial. At the later stages of the trial, more and more patients actually had already received a CDK4six.
So I think this question of the timing of when the final 410 events would occur, the modeling tries to take that into account, but that's where I think there's some uncertainty exactly when that final 410 will occur.
Okay. And remind us, do you stratify on previous CDK4six therapy? No. Okay. Okay.
Thanks very much.
Thank We have a question from Chris Shibani with Cowen. Your line is open.
Great. Thank you very much. Apologies. I wanted to go back to one quick question on the lung trial 607. You described it as a proposed trial.
Can you just remind us if you've had any interactions with the FDA to discuss this as a potential registrational trial? And then as a second follow-up, in terms of the total patient population number, comment a little bit further. I think you may have mentioned a little bit about the sizing of this study that you've selected here. A little surprised that it maybe isn't a little larger. If you could just remind us the FDA and then the trial size?
Right. So Chris, I think the slides have the actual patient numbers per arm. So it's just less than 200 patients. And it's again, someone else had asked about the detailed power, and we won't go into that on this call. We talk about that some other time.
But it's sufficiently powered, we believe, to show both that the monocyte is valid and that the high monocyte population has a better PFS than the patients with standard of care. And we have had discussions with FDA about this trial design.
Thank you. And I'm showing no further questions at this time. I'd like to turn it back to management for any closing remarks.
Sure. Thanks very much, operator. So again, let me thank everybody for joining at such a short notice. We appreciate your attention. Again, I just want to emphasize 2 points.
One is that we remain quite positive on the possibility of E2112 being a positive trial. I don't think any of us who understand the design of the trial and the Phase II are all that surprised that PFS didn't hit. We had always had that as our best case scenario, and we were prepared to file should PFS hit. But given the statistical hurdle that had to be passed, it's not that surprising that it wasn't positive. And yet, we remain quite positive on PFS.
And second, I would say I mean on OX. And then second thing I would say is, back to the earlier question, this the treatment of patients who have progressed on chemoimmunotherapy is really an area of high unmet need and an area of emerging population of patients. And so we think we're in a very good position with ENCORE 607 to potentially bring an important new option to those patients. And so we're excited to get that trial underway. I'm glad somebody asked sort of pointedly to Michael Myers, how are you going to get it done on time, but we have great confidence our clinical operations team, they always deliver for us, and so we're quite excited about getting that trial underway.
So thanks again for everybody for joining the call, and we look forward to further discussion.