Good day, ladies and gentlemen, and welcome to Syndax Third Quarter 2018 Conference Call. [Operator Instructions] As a reminder, this conference may be recorded. I would now like to introduce your host for today's conference, Melissa Forst of Argot Partners. Please begin.

Thank you, operator. Welcome, and thank you to the - thank you for everyone who's joining us on the line and the webcast this afternoon for a review of Syndax's third quarter financial and operating results. I'm Melissa Forst of Argot Partners, and with me this afternoon is Dr. Briggs Morrison, Chief Executive Officer; and Rick Shea, Chief Financial Officer. And joining during the question-and-answer session will be Michael Metzger, President and Chief Operating Officer; as well as Peter Ordentlich, Chief Scientific Officer. This call is being accompanied by a slide deck that has been posted on the company's website, so I'd please ask that you turn to the company's forward-looking statements 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 reports on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements represent the company's views as of today, November 5, 2018, only. A replay of the call will be available on the company's website at syndax.com. And with that, please turn to Slide 3, and I'll turn the call over to Briggs.

Thank you very much, Melissa, and thank you to everyone joining us on today's call and webcast. This afternoon, I will share the progress we've made during the third 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 provides a high-level summary of our corporate strategy, and I will touch on each of these strategic pillars during today's call. We just held a call on October 25 to discuss some of our programs, so my prepared remarks will be brief. Slide 4 is a summary of the near-term investment thesis for Syndax. We'd like to remind investors that 2019 is shaping up to be a very significant year for Syndax with multiple opportunities to unlock tremendous value for shareholders. There are 2 overall survival interim analyses for E2112, our Phase III trial in hormone receptor-positive HER2-negative breast cancer. And I want to again emphasize that a positive OS trial in hormone receptor-positive HER2-negative breast cancer would be a landmark result and could be transformative for Syndax and its shareholders. We also have readouts from our randomized Phase II trials, ENCORE 602 and 603, exploring the combination of entinostat and a PD-1 pathway antagonist in triple-negative breast and ovarian cancer. Both ENCORE 602 and 603 are randomized placebo-controlled trials, which allow very straightforward interpretation of trial results. If either is positive, that would represent one of the first randomized trials to validate a novel mechanism that adds to the efficacy of a PD-1 pathway antagonist. We anticipate having early clinical data from our chronic graft versus host disease trial with SNDX-6352. And finally, we are on track to file the IND and start clinical trials for…

Thank you, Briggs. Turning to Slide 14. For the 3 months ended September 30, 2018, Syndax reported a net loss of $17.3 million or $0.68 per share compared to $15.1 million or $0.68 per share for the comparable prior year period. Third quarter 2018 research and development expenses increased to $14.1 million from $12.2 million for the prior year, an increase of $1.9 million or 16% due to an increase in development activities of $0.8 million and increased employee compensation expense of $1.2 million. Increase in development activities was primarily related to the development of the Menin program and increased activities in the 602 ENCORE trial, partly offset by the completion of clinical pharmacology trials and the decrease in E2112 costs. Increase in employee compensation costs was primarily due to increased headcount. G&A expenses increased to $4.1 million during the third quarter of 2018 compared to $3.6 million for the prior year, an increase of $0.6 million or 16%. Increase was primarily due to an increase in employee-related expenses of $0.3 million and in professional and legal fees of $0.2 million. At September 30, 2018, there were 26.1 million common shares issued and outstanding, which includes the 2 million warrants held by BVF. Syndax ended the third quarter of 2018 with a cash balance of just under $90 million. And as we mentioned on our last earnings call in the third quarter, we commenced sales of our stock of our ATM, at-the-market, facility with Cowen. And this was done to solidify our balance sheet, anticipating our decision to initiate the focused biomarker-driven non-small cell lung cancer registration study. In the third quarter, we recorded $9.4 million of net proceeds from the ATM, which offset our cash burn for the third quarter. We ended the prior quarter with a cash balance…

Thanks very much, Rick. I started today's call highlighting what an important year 2019 is shaping up to be for Syndax, and I will close the call by reemphasizing that same point. We have many data readouts over the course of 2019, any of which could unlock significant shareholder value. Upcoming milestones is summarized on Slide 15. We take pride in being somewhat uniquely positioned within our industry as a small company with so much clinical data coming out over such a short time frame, including data from a Phase III trial and multiple Phase II trials over a matter of months. It will again be an extremely busy next few months for us here at Syndax. As always, I'd like to thank the team here at Syndax, our collaborators, and most importantly, the patients, trial sites and the investigators involved with our clinical programs. With that, I'd like to open the call for questions.

[Operator Instructions] Our first question comes from Bert Hazlett of BTIG.

Mike, a couple of questions. First of all, with regard to the peripheral classical monocyte biomarker, clearly, you've given us an update on your enthusiasm for non-small cell lung cancer. Could you give us a sense of where that biomarker stands in melanoma? And then I have a question on the MLLr program after that.

Right. So thanks for the question, Bert. I think as we indicated previously, we are letting the melanoma data mature. We had presented 34 patients at ASCO. We have a larger sample size, and so we're looking - we're letting that data mature and looking at monocyte biomarker for various aspects of clinical benefit. You'll remember for lung cancer, we saw both on response rate and PFS. And so we hope that by the end of this year, we'll have that data further matured and further analyzed in terms of whether the classical monocyte also helps us in melanoma.

Okay. And then with the MLLr program, again, as you mentioned, an exciting program, and it's good to see it move into the clinic. 5613 seems to be one of the portfolio. Should - could you discuss in brief characteristics that lifted 5613 to the top? And should we think about other second-gen compounds that might be active in maybe potential resistant species that arise?

Right. So 5613 came to the top for the sort of general pharmaceutical property and other characteristics of the molecule relative to the other molecules that were in the portfolio that we acquired from Allergan. At this point, actually, Bert, it's been very hard to generate resistance to these molecules. So at this point, we're not working on a resistance program simply because it's been difficult. I should say, thus far, we have not been able to generate cell lines that are resistant to this first class of molecule. So we don't have a mechanism yet to understand resistance and how we would go after it. That's a reassuring thing to us because the molecules seem to - it seems to be hard for itself to escape.

Okay. And then just one question with regard to guidance. Does R&D spend, Rick, include any spend on advancement in melanoma?

At this time, it does not.

The next question comes from Chris Shibutani of Cowen.

Just to confirm in terms of how you communicate some of the updated data points that we have coming over the next few quarters, particularly for 601, 602 and 603, obviously, you have several different partners. Can you confirm under what circumstance you'll be sharing that information? Is that going to be a corporate release? Are you waiting to provide that at a medical meeting? Is that communication that you're fully in control of as opposed to one of your partners?

So short answer is yes, we are fully in control of that as opposed to our partners, Chris.

And are you thinking about medical meeting presentations or corporate release top line results?

Right. So I would say both. And obviously, it depends on the timing of when - so for 602 and 603 randomized placebo-controlled trials, once we got that data and we had it in hand, we would, I think, be required to release that information and then present it at a medical meeting.

Okay. Curious to know. The slide that you present the ENCORE program still includes tumor mutational burden, TMB, which went through somewhat of an update at ESMO with Bristol [indiscernible] and it was unclear sort of what path that biomarker was going to continue to move forward. Can you share your own of points of views about how that particular biomarker in the level that you bleed in may play across any of these indications or combinations that obviously you're pursuing?

Sure. Peter, do you want to take that question?

Sure, yes, happy to. So we've included it partly as a way to understand the likelihood of the patient's ability to respond or not to the single-agent immune checkpoint, particularly in the lung and melanoma setting even though we know that our patients had been pretreated. So we've included those biomarkers that have been shown in other studies to be either predictive or prognostic of response to the immune checkpoint. So for us, it's really of a way to help us understand what the combination may be doing relative to the single agent in our more advanced setting. So we don't know the necessary relevance of any of these in particular to these prior pretreated patients. But as a result, we're collecting that information. I have to say because the whole lack some sequencing, a little harder to get off the samples that they don't end up being just by definition of it, more limited than the gene expression data we've collected through RNA seq or NanoString. So not too much more to add to that other than we're following the literature and just to see how it evolves with some other ongoing clinical programs.

[indiscernible] it's notable...

Pardon me, Chris, you're breaking up. Can you start again?

Ask a little bit further about the operating expense guidance and what we can believe is included in the range, particularly for instance for SG&A at the lowest possible [indiscernible] for 2019 that you spent the max on the R&D and the lowest on the two operating [indiscernible] necessarily realistic. But I'm trying to reconcile that with the potential to expand some of these programs. I can understand the emphasis on R&D. But can you give us how you came about with these operating expense ranges? And I know that resources need to be very carefully thought about, but just help us with that, the scale of spending [indiscernible].

Yes, Chris, I'll take that. So what we have happening in 2019, obviously, the accrual that's completed in E2112, so expenses will be drifting down in that clinical study. In the 601 ENCORE studies, all fully accrued, and expenses will be winding down in the first half of the year. 602 and 603 will be completed largely in the first half of the year. So all of those programs, the costs are trending down. So those will be offset by the lung study trending up in the year, but that's somewhat of a push. In the 6352 program, we actually had some significant manufacturing tech transfer costs that occurred in 2018 that won't be recurring in 2019. But we just - presently at least, we just have the GVHD study, which is relatively modest in cost. So the costs overall for that program are actually going to be down year-over-year. Costs in the Menin program obviously will be trending up. But - so overall, we'll be slightly down year-over-year. As I mentioned to Bert, that at present, we don't have a melanoma registration study in the guidance. If we decide to go forward with that study, I'll update the guidance for you.

The next question comes from Christopher Marai of Nomura.

Thanks for the color on the Menin therapeutic. I appreciate that you're looking to bring that through the clinic rather rapidly. So I was wondering given those plans, when might we see first data? Obviously, these are early data here at ASCO preclinical and you're going to start a trial in the second quarter of '19. Should we expect any data at ASH '19 on that? And then second, the early - how do you look at on the competitive landscape there in terms of both enrolling trials and perhaps IP? There's an IND expected for another similar compound first quarter of '19 by a competitor. I'm just wondering what your thoughts are around both IP and potentially our competitive trial enrollment.

Yes. So Chris, I think it's a little early for us to say whether there'll be data at ASH next year. Obviously, getting the trial up and running, opening sites, getting patients enrolled. I don't think we have quite a - we're all worked out at this point, so it's a little hard to say whether we would have data at ASH. The competitor molecule, I think you're referring to is the molecule from Kura, which I think is roughly on the same time line as ours. In our conversations with sites in getting our trial up and running, we are quite confident that we can find sites that can enroll our trial. And I think you're also asking about IP?

Yes, that's correct. Any concerns about freedom to operate or any potential concerns around IP with its compound on and maybe remind us if you have composition matter around them?

Yes. So Chris, it's Michael. So the - I don't think there's any concerns about IP. This is a separate IP from our competitor, distinct both genus and species, so I think we're in a very good competitive position and looking at late 2030s for brand-new IPs in terms of exploration. So we're in quite a good spot.

Great. And then one quick follow-up just on entinostat. Obviously, at ESMO, we saw some data where another HDAC inhibitor in entinostat breast cancer setting showed a PFS benefit in some emerging OS data. Now I was wondering if that's helped inform your view of when we may potentially see the OS read here from your entinostat trial on the ongoing Phase III, and if you had any other thoughts having reflected on that data with respect to entinostat's chance for success.

Yes. So obviously, the hydroxamic, it's not entinostat. It's a different molecule. It is a class 1 selective HDAC inhibitor and does have some both structural and pharmacologic similarities to entinostat. So I think our best predictor of how our trial will read out comes primarily from our own Phase II data. I think the fact that it's right that my team was able to show a PFS benefit that looked very similar to what we saw in our Phase II trial when entinostat is reassuring, but I don't think we - I think our predictions on when the trial will read out are more based upon our Phase II trial than on anything they presented.

Our next question from Konstantinos Aprilakis of JMP Securities.

Just your latest thoughts on whether the monocyte biomarker might be useful for patient selection outside of non-small cell lung and sort of status of any retrospective analyses performed on past clinical trials. Entinostat has an extensive sort of clinical experience. So anything you've gleaned there and an update there. And then I have a quick follow-up.

Right. So Konstan, we did mention that - as I said, the other place where we're looking at is - most actively is in the melanoma population, and that cohort is continuing to mature so that we can have enough information from the cohort on both PFS and response rate that we can then ask whether the classical monocyte is also useful in that population as it turns - as it so far has been in lung cancer. So we don't have an answer to that yet. Hopefully, by the end of this year on that trial. And what was your other question?

I just had a quick follow-up. Sort of in the pivotal trial for non-small cell lung, did you - was it discussed or have you considered sort of including KEYTRUDA monotherapy cohort in that trial? Or do you not think it's necessary sort of given wanting to validate the biomarker and compare it to standard-of-care chemo? What are your thoughts there?

Yes. So what I would say is we had that conversation with a number of lung cancer experts at World Lung when we presented our data back in September and did discuss with them the option of having a KEYTRUDA monotherapy arm. I would say they were uniformly opposed to that arm of the trial and, in fact, weren't sure they would be able to actually get it through an to IRP. To have a patient who had just progressed on the PD-1 then go on to a trial, which they get the exact same agent or an agent in the same class that they have just progressed on, they felt was a difficult thing to undertake. They also said to us that in their experience that their response rate to that retreatment, if you will, was really quite low, and they thought it was not really something they would be interested in taking part in, to be honest. So they were much more interested in the randomization, again, standard-of-care chemotherapy.

[Operator Instructions] Our next question comes from David Lebowitz of Morgan Stanley.

In the upcoming non-small cell lung cancer trial, could you just - I guess you have 2 different primary endpoints. Does the trial need to succeed in both primary endpoints in order to be considered successful?

I'll ask Michael Meyers, our Chief Medical Officer, to answer the question.

David, so in a word, yes, we would want to see positive results in both endpoints in order to declare the trial successful for the following reason, that remember, the first analysis will be an analysis between high and low monocytes. And therefore, that analysis would need to be positive in order to demonstrate that monocytes could be used to segregate and select patients. Secondly, we would want to see that in the high monocyte patients that we have selected based on the marker that we would, in fact, be able to show benefit compared to standard-of-care chemotherapy, which would be required to get the drug approved. So the first marker is - the first analysis is required to get the marker validated. The second analysis is required to show that the drug provides benefit in that patient population.

And in the - with respect to the patient, the size of each of the cohorts, was the Phase II data the basis for determining the power in the upcoming trial?

Roughly, yes, exactly. We were looking to see if we could replicate in a rigorously defined Phase II/III trial the results that we had observed in the Phase II trial.

And with respect to the 602 and 603 data, could you just run us back through the historic rationale on why KEYTRUDA was utilized in 601 with those particular tumors and why these other PD-1, PD-L1s were chosen for 602 and 603?

Yes, sure. So I think, David, if you look at our program, it's - we tried to set up relatively broad proof-of-concept program that essentially tested different tumors that have different immunologic states, if you will. So if you think about lung cancer, melanoma, at least a subset of both of those are considered to be inflamed tumors. Triple negative breast cancer tends to be excluded where you have T cells, but it sort of sits outside the tumor. Ovarian is sometimes referred to as sort of the immunologic desert where you actually don't see a lot of T cell either around the tumor or in the tumor. So there was a plan to look at different tumor types based upon their immunology. And then in conversations with different companies, different companies were interested in different tumor types. So at the time, Merck was obviously quite interested in lung cancer melanoma. Those were the 2 tumor types that they initially were studying. Roche-Genentech was interested in triple negative breast cancer. And Pfizer, as you know, has been doing work in ovarian cancer. We added in colorectal cancer with Merck later in the program, again given some of the stuff that we had seen in melanoma and the interest in colorectal cancer as a tumor type that was really non-IO responsive. So the demarcation amongst the different companies was really just the tumors that they were interested in. I would say others were interested in lung cancer, but we'd already given that to Merck. So we didn't want to do the same thing again with another company, so that's how we laid - how we ended up with the various partners. Obviously, we're very pleased with all 3 of our partners. We have wonderful partnerships, great scientific collaborations, and that's how we ended up where we are.

And I guess one last question. Could you remind us the threshold for colorectal cancer in the Simon two-stage?

So yes. So on the Simon two-stage, we're trying to - the hypothetical response rate is 15%. We're trying to exclude a lower bound of 5% in the Simon two-stage design with a 90% power and a type 1 error rate of 0.05. That's one-sided. We would require 3 of 37 responses in the first stage in order to go to a final overall study size of 84 patients.

Our next question comes from Ed White of H.C. Wainwright.

Just a quick question for Rick. You said at the ATM, you raised $9.4 million in the third quarter and $6.1 million so far in the fourth quarter. I was just wondering if you can give us the share count associated with those - with that monetary value.

Yes. Let me see if I have that handy here. Let's see. I have an overall share count, I believe, of 2.1 million shares but a 15.5 million in total. I don't know if we split it out separately by quarters. It's probably going to be in our Q that's going to be filed actually momentarily, so you can probably find it in there.

At this time, I would like to turn the call back over to Dr. Morrison for closing remarks.

Great. Thanks very much, operator, and thanks for everybody for joining us on today's call. We look forward to seeing you at various upcoming meetings. And if you have any other questions, feel free to contact us.

Ladies and gentlemen, thank you for your participation in today's conference. You may disconnect. Have a wonderful day.