Syndax Pharmaceuticals, Inc. (SNDX) Q2 2017 Earnings Report, Transcript and Summary

Good day, ladies and gentlemen, and welcome to the Syndax Second Quarter 2017 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions]. I would now like to introduce your host for this conference call, Melissa Forst, Assistant Vice President at Investor Relations at Argot Partners. You may begin ma'am.

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 second 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 on the Company's website. So I would ask you to please turn to our forward looking statements on Slide 2. Before we get 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 the Form 10-Q and other reports filed with the SEC. Any forward-looking statements represent our views as of today August 10, 2017 only. A replay of the call will be available on the company's website at www.syndax.com after the call is over. With that, please turn to Slide 3. And I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer.

Thank you, Melissa, and thank you, everyone, for joining us today for today's call. This afternoon I'll walk you through our clinical pipeline and share the progress we've made during the second quarter. Slide 3 provides a snapshot of our clinical stage programs, which include two potential best-in-class molecules; entinostat and SNDX-6352 being tested in five ongoing clinical trials across six different indications. As you can see on Slide 4, the second quarter was marked by a substantial progress, most notably in our ENCORE 601 trial. As a remainder, ENCORE 601 is our Phase 1b/2 clinical trial, evaluating the combination of entinostat plus Merck's anti-PD-1 blocking therapy, KEYTRUDA, or pembrolizumab. In May, we announced that the PD-1 refractory non-small cell lung cancer cohort satisfied the pre-specified efficacy criteria for advancement into the second and definitive stage of the Phase 2 trial. Earlier in the year, we had announced that the PD-1 refectory melanoma cohort had also satisfied the pre-specified efficacy criteria for advancement into the second stage of the Phase 2 trial. And in June, we presented positive results from the stage one of the melanoma cohort at the American Society of Clinical Oncology annual meeting. We also had a very productive Type B meeting with the FDA to review these results in melanoma patients and to discuss potential registration pathways for entinostat, including a potential path for accelerated approval. We are currently evaluating specific development options and will provide you with updates on our plans by the end of the year. Slide 5 summarizes the status of our ENCORE 601 trial. Notably, we are pleased to announce that enrolment in the second stage of the melanoma cohort of ENCORE 601, which has now enrolled a total of 34 patients, has completed ahead of schedule. We anticipate being able to share biomarker data from stage one of this cohort at the Society of Immunotherapy for Cancer annual meeting, the SITC meeting, in the fourth quarter of this year. And the full results from both stage one and stage two of this cohort at the Medical Congress in the first half of 2018. As I mentioned earlier in the call, during the second quarter, we announced that the PD-1 refractory non-small cell lung cancer cohort of ENCORE 601 had met the pre-specified objective response threshold to advance into the second stage of the Phase 2 trial. The decision to proceed to the second stage for the PD-1 refractory non-small cell lung cancer cohort used a revised criteria, which required a minimum of three responses out of 31 patients versus the previous benchmark we had discussed, which was at least two responses out of 20. This revision was made by our investigators and the Chief Medical Officer to incorporate the Phase 1b patients, who had received the 5 milligram dose of entinostat. So we have a total of 31 patients now. Enrolment in this cohort will continue until a total of 56 patients are enrolled, which we expect will occur sometime in the fourth quarter of this year. We anticipate presenting data from the full cohort at the Medical Congress in the first half of 2018. The cohort of non-small cell lung cancer patients, who are naïve to PD-1 or PD-L1 therapy, continues with the number of patients remaining on the entinostat-KEYTRUDA combination. In this cohort as well the go/no go criteria had been adjusted to include the Phase 1b patients who are treated with entinostat at five milligram. So for this cohort to the revise criteria now requires a minimum of four responses out of 17 patients versus the previous communicated benchmark of at least three responses out of 13 to determine whether or not to progress this cohort into the second stage. While we had hoped to make the decision on this cohort by the end of June, we now anticipate the decision will occur no later than the end of the year. We anticipate sharing data from stage one of both ENCORE 601 non-small cell lung cancer cohort at SITC in the fourth quarter of this year. Finally, we are pleased to note that our first patient has been dosed in the ENCORE 601 cohort enrolling patients with microsatellite stable colon cancer. As with the rest of the ENCORE 601 cohorts, the trial will employ a Simon two-stage design, with enrollments set at 13 patients in the first stage. A minimum of two confirmed objective responses are required to proceed to the second stage, which would then enroll additional 21 patients for a total of 34. We anticipate a decision on whether to advance the colorectal cohort into the second stage of the trial sometime in the first half of 2018. We believe that the microsatellite stable colorectal cancer population represents a significant unmet need accounting for approximately 85% of the overall colorectal cancer population. And they have been minimal responsive to anti-PD-1 monotherapy. We expect that the current single arm trial design could rapidly provide us with a meaningful signal in the first half of next year that could inform our development strategy in this indication. Shifting gears back to melanoma for a minute. On Slide 6, we illustrate what we believe is the clear unmet need for new treatment options for the roughly 10,000 melanoma patients, who fail the PD-1 antagonist, either given alone or in combination with a CTLA-4 inhibitor. Despite the advances made over the past two years and the availability of a number of new medicines for patients with metastatic melanoma, we believe a significant unmet need remains for patients whose disease has continued to progress despite these approved therapies. I'd like to now briefly review the remainder of the ENCORE program. On Slide 7, we depict the trial designs for our ENCORE 602 and ENCORE 603 trials. ENCORE 602 is a Phase 1b/2 trial exploring the combination of entinostat with Roche/Genentech's anti-PD-1 antibody, TECENTRIQ, in women with metastatic triple negative breast cancer, who have received one or two prior lines of systemic therapy. The primary endpoint of the trial is progression-free survival, with secondary endpoints evaluating overall response rate and overall survival. Enrollment in the randomized Phase 2 portion of the trial after five milligram dose of entinostat remains ongoing and we anticipate to complete enrollment in the fourth quarter. ENCORE 603 is our Phase 1b/2 trial testing entinostat in combination with BAVENCIO, an anti-PD-L1 antibody developed by the Pfizer/Merck KGaA alliance in women with advanced ovarian cancer, who have previously received three to five lines of therapy. Similar to ENCORE 602, the ENCORE 603 trial design includes the safety if running components followed by a randomized Phase 2 component. As with ENCORE 602, the primary endpoint of the Phase 2 part of the trial is PFS, with secondary endpoints evaluating overall response rate and overall survival. Enrollment in the randomized Phase 2 portion of the trial at the five milligram dose in entinostat began last month and we expect to complete enrollment sometime in the first half of 2018. Next turning to Slide 8, we'd like to update you on E2112, our ongoing Phase 3 registration trial of entinostat plus exemestane, an aromatase inhibitor, in 600 patients with advanced hormone receptor positive, HER2 negative breast cancer who progressed following treatment with standard of care. E2112 represents the first Phase 3 trial involving a novel mechanism of action in this setting since the approval of agents targeting CDK4/6. We are conducting this trial in collaboration with the ECOG-ACRIN Cancer Research Group and the National Cancer Institute under a special protocol assessment with the FDA. Notably the terms of this special protocol assessment allows for a potential registration filing on the basis of a positive outcome for either PFS or overall survival. As of the end of July of this year, 78% of the patients have been enrolled and ECOG has advised us that they anticipate their PFS analysis to be available in the first half of 2018, directly following the completion of enrollment. As a reminder, the FDA has granted the combination of entinostat and exemestane Breakthrough Therapy Designation for hormone receptor positive, HER2 negative breast cancer based upon positive results from our Phase 2b clinical trial, where treatment with entinostat plus exemestane demonstrated approximately an eight-month improvement in overall survival versus exemestane alone. As shown on Slide 9, we believe that entinostat had blockbuster potential as a second or third line therapy for hormone receptor positive, HER2 negative metastatic breast cancer. We estimate that there are approximately 34,000 patients who want to receive hormone therapy after failing first line therapy and who could therefore potential be eligible to receive entinostat. Based on feedback from ECOG-ACRIN, we anticipate that about a third or more of the patients enrolled in the E2112 trial will have previously received a CDK4/6 inhibitor and will provide initial evidence of entinostat efficacy in this significant and growing patient population. Let me now turn to SNDX-6352, our monoclonal antibody therapy targeting the CSF-1 receptor. We view SNDX-6352 as a potential best-in-class therapeutic candidate because of its unique profile that includes its high binding affinity, it's ability to prevent binding of both ligands, that is both IL-34 and CSF-1 to the CSF-1 receptor and its potential synergistic activity with other therapeutic class. As depicted on Slide 10, SNDX-6352 functions by blocking the ligand binding domain of the cell surface protein receptors, CSF-1R, which plays a critical role in regulating proliferation, survival and differentiation of tumor-associated macrophages. Tumor-associated macrophages are immunosuppressant cells found in the tumor microenvironment that can inhibit the ability of tumor infiltrating lymphocytes to attack and kill tumor cell. We believe that SNDX-6352 has potential to be used in combination with either checkpoint inhibitors, cell therapy, chemotherapy or radiotherapy, due to the potentially complementary or synergistic effects of such combinations. SNDX-6352 may also be synergistic with entinostat, which has been shown in preclinical experiments to inhibit two other clinically immunosuppressive cells in the tumor microenvironment the myeloid derived suppressor cells and regulatory T cells. We believe that more effective treatment of a variety of cancers will necessitate novel combination strategies to overcome the intense immunosuppression in the tumor microenvironment. The Phase 1 single ascending dose trial of SNDX-6352 in healthy volunteers has completed and we anticipate presenting the results in the fourth quarter of this year. Additionally we anticipate starting the multiple ascending dose trial later this quarter in patients with various solid tumors. Let me pause here and turn the call over to Rick Shea, our Chief Financial Officer to discuss our financial results and update you on our balance sheet.

Thank you, Briggs. Turning to Slide 11. For the three months ended June 30, 2017, Syndax reported a net loss of $13.6 million, or $0.70 per share, compared to $8.4 million, or $0.47 per share, for the comparable prior year period. Our research and development expenses in the second quarter increased to $9.6 million from $6.1 million from prior year period, primarily due to increased clinical trial activities of $2.3 million, employee compensation expense of $0.8 million and legal and consultant expenses of $0.6 million. The increase in clinical trial activities was primarily related to the additional cohorts added to ENCORE 601; increased enrolment in the 602 and 603 studies; costs related to 6352, as well as clinical pharmacology trials in CMC activities. The increase in employee compensation cost was primarily due to increased headcount. Our G&A expenses were $4.3 million during the second quarter compared to $2.8 million for the comparable prior year period, primarily due to an increase in employee compensation of $1.0 million and an increase in consulting expenses of $0.4 million. The increase in employee compensation was primarily due to an increase in non-cash stock-based compensation of $0.6 million and an increase of $0.4 million due to increased headcount. There were 22.2 million common shares outstanding at June 30, 2017 and 24.3 million shares outstanding shares on a fully diluted basis. Additional financial details will be available in our 10-Q, which will be filed this week. Syndax ended the quarter with a cash balance of $130 million, which we believe is sufficient to fund development into 2019, enabling us to reach key milestones. In this figure are $49 million in proceeds generated from the successful public offering we completed in May. The offering helped further strengthen our shareholder base and extend our financial runway through significant value inflection points in 2018 and into 2019. Looking ahead, we expect R&D expenses for the third quarter to be in the range of $12 million to $14 million and total operating expenses between $16 million and $18 million. For the full-year, we expect the R&D expenses to be between $46 million to $51 million and total operating expenses to come in between $63 million and $68 million. Now I'd like to turn the call back over to Briggs.

Thanks a lot, Rick. Looking ahead, we anticipate several key upcoming milestones summarized on Slide 12. For ENCORE 601 program, completion of enrollment in the second stage of the refractory non-small cell lung cancer cohort is expected by the end of the year. For the PD-1/PD-L1 naïve non-small cell lung cancer, we expect to announce when the cohort has achieved at pre-specified efficacy criteria for advancement by the end of the year. And for the colorectal cohort, we expect the go/no go decision for stage two to occur in the first half of 2018. We anticipate sharing the data from stage one of both non-small cell lung cancer cohorts, as well as biomarker data from stage one of the melanoma cohort at SITC in the fourth quarter. We also anticipate sharing data from the full cohort of both the refractory non-small cell lung cancer population and the refractory melanoma population and appropriate Medical Congress in the first half of 2018. Enrollment in ENCORE 602 is anticipated to complete during the fourth quarter of this year, and for ENCORE 603, we expect enrollment of the Phase 2 portion to complete in the first half of 2018. For E2112, our Phase 2 registration trial of entinostat in hormone receptor positive, HER2 negative breast cancer or at ECOG the PFS analysis is expected to be available in the first half of 2018 directly following completion of enrollment. And finally, we expect to advance SNDX-6352 into a multiple ascending dose trial in third quarter and anticipate presenting our results from the single ascending dose trial in the fourth quarter of this year at SITC. In summary, on Slide 13, we continue to advance the development of two potential best-in-class assets in five clinical trials across six different indications. Particularly excited about the initial clinical evidence we have seen in the refractory melanoma and non-small cell lung cancer cohorts of ENCORE 601 that provide initial evidence for entinostat potential to reverse resistance to immune checkpoint inhibitors like PD1 antagonists and provided a new treatment options for patients who have very limited therapeutic options. In addition, as we have demonstrated through our in-licensing of SNDX-6352, we continue to pursue business development opportunities that offer an attractive risk reward what strong strategic fit for Syndax. As always, I would like to thank the team here at Syndax, our collaborators, and most importantly, the patients, the trial sites and the investigators involved with our clinical program. With that, I'd like to open the call for questions.

[Operator Instructions]. Our first question comes from Chris Shibutani with Cowen.

Thank you very much. Appreciate the update. If you could give us a better sense following your Type B meeting looking at entinostat combination with the checkpoint inhibitor, you mentioned evaluating options without - I realize you're still assessing these. But can you give us a sense for what some of the potential options might be?

Yes, Chris, what I can say is that it was an extremely productive meeting. We, in our conversation with them, got a very clear range of options that would allow accelerated approval as well as a range of options that would allow of course full approval. And I'm not really at liberty to say too much more about what all those options are. We really need to systematically work through all of them and make a decision. We are doing that as expeditiously as we can and we'll get back to you once we have a clearer path.

Okay, fair enough. Then on - if I can just ask for ENCORE 602, triple negative breast with Genentech/Roche and 603 ovarian with Merck/Pfizer. I don't recall if we have seen Phase 1b data. In your anticipated upcoming events, we do have Phase 2 data at that you will talk about towards the end of '18 I see. Have you reported Phase 1b, or is there an opportunity to learn what those results have looked like? I realize the one - not many patients but nonetheless.

Right. So we have not presented the Phase 1b portion, and at this time I don't think the team is anticipating presenting that, because as you say, the relatively limited number of patients really just to confirm the safety. So at this point, we don't have a plan to present that separate from the results of the randomized Phase 2 portion?

Okay, great. Thank you very much.

Our next question comes from Bert Hazlett with BTIG.

Yes, thanks for taking the questions. Could you…

You broke up, Bert. We can't hear you.

Did you want me to move onto the next question and maybe Bert will queue back up.

Yes, why don't we do that?

Our next question comes from David Lebowitz from Morgan Stanley.

Hi. This is Cyrus on for David. Given the characteristics that led you to initiate the colorectal cohort, are there any other cancer types that would be particularly amenable for this entinostat checkpoint combo?

Thanks for the question. Cyrus. So we have now, we think, between lung cancer and melanoma, colorectal, triple negative breast and ovarian, a abroad sampling of the different types of tumors from an immunologic point of view. So there are other tumors that based upon the biology that we think is operative in colorectal cancer. But at this stage of the game, I think our strategy would be to let these five tumor types play out, see what we learn, and based upon that, there are other tumor types that we would think about but we don't have any intentions of starting any of those additional trials until we see the data from the ones we have ongoing.

Got it. Thank you.

Our next question comes from Tony Butler with Guggenheim Securities.

Yes, thanks very much. Briggs, you commented on a biomarker or biomarkers that you would present or discuss at SITC. Curious if you would care to elaborate a little bit more on what exactly that might be - even characteristically what that might be? I have two other questions if I can go ahead and give those, if I may. And the second is, if you recall the - which I'm sure you do, the number of patients enrolled in E2112 at the end of April was 440. So I guess that leaves about 20 or roughly nine a month. To get to the 600 - and maybe I'm just being picky here, certainly would take longer than the end of the first quarter for '18. And I know you don't have control over but perhaps you can comment on it. And then finally can you provide any information about the pathology or at least the - any information about the CRC patients that are being enrolled? Anything to do with ECOG scores, or more importantly, what their prior treatment may have been etcetera. That would be really helpful. Appreciate it.

Sure. So let me start with the biomarkers at SITC. I think we've been communicated with folks that we are trying to get pre and post-biopsies. We've been quite successful in doing that in a large number of the patients. And as you can imagine, some of the things that we would look at include their PD-L1 status before they go on therapy and after they go on therapy. There is the inflamed versus non-inflamed signature that Merck has developed that we look at in patients before and after therapy. Some of the standard things you would think about looking at CD8-positive T cells, myeloid-derived suppressor cells. So those are the ones that are, I think, I can say for sure we will have in the presentation that we'll be presenting at SITC. There are other exploratory things that I'm not sure we'll have ready for SITC, but those basic ones I think we'll have in place. Your second question about 2112 and the enrollment. The enrollment in 2112 varies by month. I would say it's not a straight line. Some months we get better enrollments, sometimes we get less. So I think your math act on the - perhaps the last three months matches with our math. I think if we look at the year-to-date over the calendar year, we are running probably closer to 12 patients per month, which gets us in the first half. And if we look at the enrollment in earlier point in the trial when it was even more than 12 months, that could bring things in yet earlier still. So as we look back over the history of the trial and speak with ECOG about what they are seeing, what they are hearing from their sites, we are still guiding towards the first half of '18. Your last question about the types of patients who are being enrolled in colorectal cancer, I'll let Michael Meyers answer that.

Yes, so Tony you addressed ECOG status. Predominantly these would be ECOG zero and one patients, similar to the patients who were enrolled in the cohorts - the cohorts of 601 and they would have received prior standard of care chemotherapy potentially Avastin. However they would have not received a prior checkpoint inhibitor or other immunotherapy.

And Michael, they would have progressed beyond whatever that SOC is. Is that - that's the patient that's coming to you through selecting?

Absolutely, yes. They would have progressed on prior therapy.

That's great. Michael, thank you, and Briggs, appreciate it.

Okay.

Our next question comes from Joel Beatty with Citi.

Hi, thanks for taking the questions. The first question is a follow-up question on the biomarker that will be presented at SITC. Is that biomarker that is something that you expect could play a role in the upcoming trials for melanoma and either helping to identifying patients to enroll in the trial or in other manner?

Yes, Joel, thanks for the question. At this stage of the game, we think we do not have a beat on a biomarker that would be used for patient enrollment. I think - again the 13 patients that we have, it's more understanding the biology of what's going on with entinostat therapy. But I don't think we are yet at a point that we would have something that we would use as a selection criteria for enrolling patients.

Okay, great. And then one other question on the Phase 1b patients that are now being included in the go/no go decisions. Are you able to share any information on what the data was in the Phase 1b portion?

So the initial Phase 1b data was presented at SITC back in November of 2016. We are more than happy to send you that poster. In that report, we had both three milligrams and five milligrams because we were doing the dose escalation safety portion. We've only included the patients dose that's five milligrams in this expanded definition of the patients we are using to make the decision.

Okay, got it. Thank you.

Our next question comes from Mike King with JMP Securities.

Hi. Good afternoon, guys. Thanks for taking the question. Couple of brief ones, as many of my questions have been answered. Briggs, I was wondering if you can just talk about the slight stretch out in the timing on the non-small cell lung cohort [indiscernible] non-small cell seems to stretch down a little bit. Can you talk about what may account for that?

Sure, Mike. So when we finished enrolling the cohort, the logic behind our projections of when we thought we would be able to read out were these are patients who had failed chemotherapy and progressed on a PD-1 or PD-L1 antibody. And so we figured if this drug is not working it should progress - sorry, this is a naïve cohort, right.

Naïve, yes.

Yes, we figured that patients - the responses that you see to PD-1 monotherapy generally occur relatively quickly. I think 90% of them are within six months. So we figured we probably have that declared by the end of the second quarter. In essence, what's happened is we have patients on trial. And so if you think about the bookings of declaring this, you either have to have now four responses or you have to have 14 patients progress and we just haven't it either one of those bookends, so we can't say yes, the cohort has met its criteria and can reopen, nor can we say it's definitely not going to meet its criteria because we still have patients on trial. So we are sort of in that gray zone in the middle. Some of the patients obviously are still on trial with stable disease but have not yet responded. And so it's just a matter of sort of seeing how that plays out.

Okay. And I guess, given - I guess, that's kind of your best estimate, given the time of the year that we're in and the likes of that.

That's our best estimate based upon our review of the patients who are on the trial and when those patients might have additional evaluations and when they could be either potentially declare themselves as progressors or responders.

Right. Okay, and then on the flip side, the melanoma cohort seems have gone much more rapidly. Is that because there is a larger pool of potential patients there or how are they progressing, a little more quicker than you expected or what's happening there?

So I think the enrollment there has gone faster than we anticipated and I think there is two reasons for that. One is this is clearly an unmet need. There are a lot of these patients that we spent quite a bit of time at ASCO meeting with melanoma physicians and they all see a lot of these patients. So they are in need. And I think second thing is we have promising initial data. And when you have promising initial data people, get excited about your program and want to put patients on trial. So I think our team has done a great job of identifying good investigators, and unfortunately there are number of these patients and I think because of the initial data we had, people are quite excited. And so it's enrolling really quite quickly.

Okay. Thank you for that color. And then I just wanted to flip quickly to 6352. There are a number of assets in this space and they all appear to have some degree of ocular talks. And I'm just wondering, given your unique mechanism of action, is that a lesser, a greater or similar concern when it comes to safety and tolerability with the other CSF-1R blockers? Thanks.

Yes, I'll let Michael Meyers take that one.

Yes. I think based on what we know that our molecule compared to competitors, there is no reason to believe that we have any greater risk of ocular toxicity. On the other hand, we don't know that we have a lesser likelihood of ocular toxicity. So I think it's really early remember the single ascending dose trials administered only one dose to healthy volunteers. I can tell you that we didn't see anything that was totally alarming in that case, and therefore we are very comfortable moving forward to the multiple ascending dose trial?

And when will that start, Michael?

That will start this month. We expect that we would have the first patient in either late this month or sometime early next month.

Right. Thanks for taking my questions.

Our next question comes from Bert Hazlett with BTIG.

Yes, thanks for taking the question and my apologies for the phone snafu earlier. So my question is, in general, as you evaluate the non-small cell lung cancer cohorts and then as you are evaluating the melanoma discussions you've had with your - with FDA. Is part of the analyses really examining the field and how the field is evolving, or is it much more a consideration of how your drug is performing?

Yes, Bert, thanks for that question. So it's a combination of both. So I think in the melanoma space, there really - best we can tell from the competitive landscape, there really aren't any other agents much further ahead in development in this population than we are. And there really, as I mentioned earlier with the enrolment, I think it's clear unmet need. So melanoma it's really just we have good discussion with FDA. I think we had a range of options and we are going through those. I think in non-small cell lung cancer, I would say particularly in the - with reference to the naïve population, clearly the field is progressing quite rapidly, initially with Merck's approval of pembro for the PD-L1 high population, and more recently, their approval in combination with pemetrexed and platinum for essentially all, including the PD-L1 lows. So that I think is a notable competitive dynamic. There is more data coming out from what we understand this year from the Roche trials using chemotherapy in combination with their PD-L1 antibody and additional data on the CTLA-4 combination. So I think in the first line setting, the bar is moving through the approval of some of these other combinations and we are quite aware of that and taking that into account as we think about future development.

Okay. Thanks for the color.

The next question comes from Christopher Marai with Nomura.

Hi guys. Thanks for taking the questions. I'm just wondering if you could further elaborate perhaps on some of the considerations that you're thinking about and some of the gating factors in terms of those options you are evaluating, post the FDA discussion and the path forward there in melanoma. And then secondarily, in terms of the CSF-1R, may be if you'd elaborate a little more on the path forward and new indications there? Is that something that you expect to use combo with PD-1 agents as has been done by others, or would you be looking at some other potentially complementary approaches with other therapeutics? Thank you.

Great. Thanks Chris. So from the way we are thinking about the feedback we got from FDA, I think, is relatively conventional, which is to look at time, cost, risk and value. And so as we look at each one of the different options that we discussed with them, as you could imagine, some of those options are a little high risk, some of them are lower risk, some of them are faster, some of them are slower, some cost more, some cost less. And so we are trying to balance all of those things in a way that we think is appropriate and then we'll make a decision on how to take that forward. So as I said earlier from - with Chris's question, I just can't go into too much detail on what all those options are. But we are trying to balance all of those various aspects. The question on what will we do with our CSF-1R antibody? We have not really decided or I should say we haven't communicated what we've decided. We are looking at lots of opportunities. As I mentioned in my prepared remarks, there is good preclinical data on, obviously combination with PD11 or PD-L1s and there are other folks doing those experiments. Our understanding is some of that data might now be at SITC from the collaboration with Five Prime and BMS. There is also preclinical data to support combinations with chemotherapy. There is data to support combinations with radiotherapy. There is data to support combinations with cell therapy. And we are doing some preclinical work to see whether the combination might work when we combine it with entinostat. So I guess, the challenge here is there is lots of different opportunities and we want to sort through all of those before we make a decision or decisions, we may do a couple of things. Of course it will be quite interesting to all of us to see what our competitors are seeing when they combine with PD-1 or PD-L1.

Great. Thank you.

The next question comes from Hartaj Singh with Oppenheimer.

Great. Thank you, guys. Can you hear me?

We sure can, Hartaj. Go ahead.

Great. Thank you. Thanks everyone. So just a question on colorectal cancer. What's interesting to me is that unlike non-small cell land cancer melanoma, it's less well-developed in the IO area, where there is a lot of activity going on. I mean, there was a MEK inhibitor plus I believe Roche's PD-L1 where they had good Phase 2 data and they were able to accelerate. Actually it was earlier than Phase 2 and accelerated into Phase 3 very quickly. So I guess could you just describe sort of what's the kind of patient population you're looking at colorectal cancer? And if you do get good data, is there a possibility, like melanoma, to accelerate that trial? And then just got a quick question on 2112 after that. Thank you.

So I think Michael earlier described in type of patients we are enrolling. These are patients who have progressed after standard of care. And unfortunately they are in desperate need of new therapies. We agree with you that the PD-1 alone is - again we'd careful to limit it to the sort of running the mill colorectal that Michael said like stable colorectal cancer, hasn't really been all that promising at all. The combination with the MEK inhibitor did look quite interesting in the early Roche data. And so that's a clue that perhaps there are ways that some of these tumors are immuno-responsive and there may be ways to trigger the immune system to work against them. So that's part of the rationale for us doing this. But we do agree with you that it is an area of unmet need and with promising early data, there could be similar to melanoma, I suspect there will be both accelerated and for approval path. Then you said you had a question on 2112?

Yes, just - thanks, Briggs. Yes, I mean just to me that's really interesting on the colorectal side to be able to go down that path. And then just on 2112, I know that there was another CDK4/6 approved recently. I'm sure the trial has fairly planned for the first line therapy. Any changes that you see from the new CDK4/6 being approved and does that change anything or not really that sort of in the protocol and you expect that to just sort of move along? Thank you.

So I'll let Michael Metzger take that one.

Yes, thanks Hartaj. I think - look, these CDK4/6 inhibitors are going after first line therapy and I think from our perspective, it doesn't really change the dynamic so much. There is utilization first and second line to say, but we do think all three will ultimately fight for first line therapy. So from our perspective, we are positioning ourselves second, third, fourth line and this doesn't change the dynamic from a commercial perspective really at all for us.

Got it. I mean, I guess, what I was getting at is that you won't - I mean, you would expect to see a certain percentage of your patient population being exposed to CDK4/6 before in your trial and that problem shouldn't change that much even with the new one in the first line right?

Right. I think - thanks for clarifying. What we are seeing in our trial, roughly 30% to 50% of our patients will have CDK 4/6 inhibitors. So most of that is Ibrance. It could be some of the new approved agents as well as the trial goes on. But yes, so we have a quite a bit of our population has already gone through CDK4/6, which is of course very important for physicians in terms of their choices of next line therapy.

Great. Fantastic. Thank you, Michael. Thanks all.

And I'm not showing any further questions at this time. I'd like to turn the call back over to our host.

Well, thanks again everybody for joining us. I hope you're having an enjoyable summer. And any other questions, you have just let us know. Thanks again.

Ladies and gentlemen, that does concludes today's presentation. You may now disconnect and have a wonderful day.