Syndax Pharmaceuticals Inc (SNDX) 2017 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Syndax Second Quarter 2017 Conference Call. (Operator Instructions) I would now like to introduce your host for today's conference, Melissa Forst, Assistant Vice President of 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 Syndax's second quarter financial and operating results. I'm Melissa Forst of 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'd ask you to please 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 risks discussed in the Risk Factors section in the company's most recent quarterly report on 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 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 to 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 2 potential best-in-class molecules, entinostat and SNDX-6352, being tested in 5 ongoing clinical trials across 6 different indications.

As you can see on Slide 4, the second quarter was marked by substantial progress, most notably in our ENCORE 601 trial. As a reminder, ENCORE 601 is our Phase Ib/II 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 prespecified efficacy criteria for advancement into the second and definitive stage of the Phase II trial.

Earlier in the year, we had announced that the PD-1 refractory melanoma cohort had also satisfied the prespecified efficacy criteria for advancement into the second stage of the Phase II trial. And in June, we presented positive results from the Stage 1 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 we'll proved you with an update on our plans by the end of the year.

Slide 5 summarizes the status of our ENCORE 601 trial. Notably, we're pleased to announce that enrollment 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 1 of this cohort at Society of Immunotherapy for Cancer Annual Meeting, a SITC meeting in the fourth quarter of this year and the full result from both Stage 1 and Stage 2 of this cohort at a 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 prespecified objective response threshold to advance into the second stage of the Phase II 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 3 responses out of 31 patients versus the previous benchmark we had discussed, which was at least 2 responses out of 20.

This revision was made by our investigators and the Chief Medical Officer to incorporate the Phase Ib quotations who had received the 5-milligram dose of entinostat. So we have a total of 31 patients now.

Enrollment 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 a Medical Congress in the first half of 2018.

The cohort of non-small cell lung cancer patients who are naive to PD-1 or PD-L1 therapy continues with a 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 Ib patients who were treated with entinostat at 5 milligrams.

So for this cohort, the revised criteria now requires a minimum of 4 responses out of 17 patients versus the previous communicated benchmark of at least 3 responses out of 13 to determine whether or not to progress this cohort into the second stage.

While we had hoped to make a decision to -- 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 1 of both ENCORE 601 non-small cell lung cancer cohorts at SITC in the fourth quarter of this year.

Finally, we're pleased to note that our first patient has been dosed in the ENCORE 601 cohort enrolling patient microsatellite stable colorectal cancer. As with the rest of the ENCORE 601 cohorts, the trial will employ a Simon two-stage trial with enrollment set at 13 patients in the first stage. A minimum of 2 confirmed objective responses are required to proceed to the second stage, which would then enroll an 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 minimally 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 a PD-1 antagonist, either given alone or in combination with a CTLA-4 inhibitor.

Despite the advances made over the past 3 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 Ib/II trial exploring the combination of entinostat with Roche-Genentech's anti-PD-L1 antibody, TECENTRIQ, in women with metastatic triple negative breast cancer who have received 1 or 2 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 II portion of the trial at the 5-milligram dose in entinostat remains ongoing, and we anticipate to complete enrollment in the fourth quarter.

ENCORE 603 is our Phase Ib/II trial testing entinostat in combination with BAVENCIO, a anti-PD-L1 antibody developed by the Pfizer/Merck KGaA alliance in women with advanced ovarian cancer who have previously received 3 to 5 lines of therapy.

Similar to ENCORE 602, the ENCORE 603 trial design includes a safety [run-in] component followed by a randomized Phase II component. As with ENCORE 602, the primary endpoint of the Phase II positive trial is PFS. The secondary endpoint evaluating overall response rate and overall survival. Enrollment in the randomized Phase II portion of the trial at the 5-milligram dose of 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 III registration trial of entinostat plus exemestane, an aromatase inhibitor, in 600 patients with advanced hormone receptor positive, HER2-negative breast cancer who have progressed following treatment with standard of care.

E2112 represents the first Phase III trial involving a novel mechanism of action in this setting since the approval of agents targeting CDK4/6. We're 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 the special protocol assessment allow 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 the 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 IIb clinical trial for treatment with entinostat plus exemestane demonstrated approximately an 8-month improvement in overall survival versus exemestane alone.

As shown on Slide 9, we believe that entinostat has 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 go on to receive hormone therapy after failing first-line therapy and who could, therefore, potentially be eligible to receive entinostat.

Based on feedback from ECOG-ACRIN, we anticipate that about 1/3 or more of the patients enrolled in the E2112 trial who have previously received a CDK4/6 inhibitor and will provide initial evidence of entinostat's 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, its ability to prevent binding of both ligand, that is both IL-34 and CSF-1 to the CSF-1 receptor and its potential synergistic activity with other therapeutic classes. As depicted on Slide 10, SNDX-6352 functions by blocking the ligand binding domain of the cell surface protein receptor, 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 cells.

We believe that SNDX-6352 has the 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 2 other critically immunosuppressant cells in the tumor microenvironment, the myeloid-derived suppressor cells and regulatory T cell. 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 I 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 a 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. Now turning to Slide 11. For the 3 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 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 enrollment in the 602 and 603 studies, costs related to 6352 as well as clinical pharmacology trials and CMC activities. The increasing 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 noncash 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 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. Included 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 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 milestone summarized on Slide 12.

For our 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 naive non-small cell lung cancer, we expect to announce whether the cohort has achieved the prespecified efficacy criteria for advancement by the end of the year. And for the colorectal cohort, we expect a go/no go decision for Stage 2 to occur in the first half of 2018.

We anticipate sharing the data from Stage 1 of both non-small cell lung cancer cohorts as well as biomarker data from Stage 1 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 at an 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 II portion to complete in the first half of 2018.

For E2112, our Phase II registration trial of entinostat in hormone receptor positive, HER2-negative breast cancer, according to 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 advanced SNDX-6352 into a multiple ascending dose trial in the third quarter and anticipate presenting results from the single ascending dose trial in the fourth quarter of this year.

In summary, on Slide 13, we continue to advance the development of 2 potential best-in-class assets in 5 clinical trials across 6 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's potential to reverse resistance to new checkpoint inhibitors like PD-1 antagonists and provide a new treatment option 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 and 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 programs.

With that, I'd like to open the call for questions.

(Operator Instructions) Our first question comes from Chris Shibutani with Cowen.

Appreciate the update. If you could give us a better sense following your Type B meeting. Looking at the entinostat combination with a 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're doing that as expeditiously as we can, and we'll get back to you once we have a clearer path.

Okay, fair enough. And then on -- if I could 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 Ib data. In your anticipated upcoming events, we do have Phase II data that you'll talk about towards the end of '18, I see. Have you reported Phase Ib? Or is there an opportunity to learn what those results would look like. I realize there weren't that many patients, but nonetheless.

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

Our next question comes from Bert Hazlett with BTIG.

Could you...

(technical difficulty)

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

Our next question comes from David Lebowitz with Morgan Stanley.

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, melanoma, colorectal, triple negative breast and ovarian, a broad 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 5 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 intention to starting any of those additional trials until we see the data from the ones we have ongoing.

Our next question comes from Tony Butler with Guggenheim Securities.

Briggs, you commented on a biomarker or biomarkers that you would present or discuss at SITC. And I'm 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 2 other questions, if I can go ahead and get those in, if I may. The second is, if you recall, 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 28 or roughly 9 a month. To get to 600 and maybe I'm just being picky here, it certainly would take longer than the end of the first quarter for '18. And I know you don't have control over it 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, et cetera, that would be really helpful. Appreciate it.

Sure, so let me start with the biomarkers at SITC. I think we've been communicating 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're on a therapy. There is the inflamed versus noninflamed 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+ 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 basics ones, I think, we'll have in place. Your second question about 2112 and the enrollment. The enrollment in 2112, it varies by month. I would say it's not a straight line. Some months, we get better enrollment, sometimes we get less. So I think your math on perhaps the last 3 months matches with our math. I think if we look at the year-to-date over the calendar year, we're running probably closer to 12 patients per month, which gets us in the first half. And if we look at the enrollment at an earlier point in the trial, when it was even more than 12 per month that could bring things in yet earlier still. So as we look back over the sort of history of the trial and speak with ECOG about what they're seeing, what they're hearing from their sites, we're 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's status. Predominantly, these would be ECOG 0 and 1 patients, similar to the patients who are involved in the cohorts, the other cohorts of 601. And they would have received prior standard of care chemotherapy, potentially Avastin, however, they would not have received a prior checkpoint inhibitor or other immunotherapy.

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

Absolutely, yes. Yes, they would have progressed on prior therapy.

Our next question comes from Joel Beatty with Citi.

The first question is on -- a follow-up question on the biomarker data that will be presented at SITC. Is that biomarker data something that you expect could play a role in the upcoming trials for melanoma in either helping to identify patients to enroll in the trial or another manner?

Yes, Joel. Thanks for the question. At this stage of the game, we think we do not have a bead on a biomarker that would be used for patient enrollment. I think, again, of 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're yet at a point that we would have something that we would use as a selection criteria for enrolling patients.

Great. And then one other question on the Phase Ib 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 Ib portion?

So the initial Phase Ib data was presented at SITC back in November of 2016. We're more than happy to send you that poster. They were -- in that report, we had both 3 milligrams and 5 milligrams because we were doing the dose escalation safety portion. We've only included the patients dosed at 5 milligrams in this expanded definition of the patients we're using to make the decision.

Our next question comes from Mike King with JMP Securities.

A couple brief ones as many of my questions have been answered. Briggs, I was wondering if you could just talk about the slight stretch out in the timing on the non-small cell lung cohort -- [on the] non-small cell seems to have stretched out 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, where these are patients who have failed chemotherapy and progressed on a PD-1 or PD-L1 antibody. And so we figured if this drug is not working, you should progress -- I'm sorry, this is a naive cohort?

Naive cohort.

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 6 months. So we figured we'd 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 bookends of declaring this, you either have to have the now 4 responses or you have to have 14 patients progress. And we just haven't hit 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're 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. I guess given -- I guess you -- that's kind of your best estimate given the time of the year that we're in and the like of that.

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 either potentially declare themselves as progressors or responders.

Right. Okay. And then on the flip side, the melanoma cohort seems to have gone much more rapidly, is that because there's a larger pool of potential patients there? Or 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's 2 reasons for that. One, is this is clearly at an unmet need. There a lot of these patients. We've spent quite a bit of time at ASCO meeting with melanoma physicians and they all see a lot of these patients. So they're a 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 a number of these patients. And I think because of the initial data we had, people are quite excited and so it's enrolled really quite quickly.

Okay. And then I just wanted to flip quickly to 6352. There are a number of assets in the 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 a similar concern when it comes to safety and tolerability with the other CSF-1R blockers?

Yes, I let Michael Meyers take that one.

Yes, I think based on what we know about our molecule compared to competitors, there's 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.

Our next question comes from Bert Hazlett with BTIG.

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're evaluating the melanoma discussions you've had with your -- with FDA, is part of the analysis really examining the field and how the field is evolving? Or is it much more a consideration of how your drug's performing?

Yes. Bert, thanks for the question. So it's a combination of both. So I think in the melanoma space, the -- they're 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. So -- and it really is, as I mentioned earlier with the enrollment, there's clear unmet need. So melanoma, it's really just we have good discussion with FDA. I think we have a range of options, and we're going through those. I think in non-small cell lung cancer, I would say particularly in the -- with reference to the naive 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 potentially all, including the PD-L1 load. So that I think is a notable competitive dynamic. There's 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're quite aware of that and taking that into account as we think about future development.

Our next question comes from Christopher Marai with Nomura.

I was 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're evaluating post the FDA discussion and the path forward there in melanoma. And then secondarily, in terms of the CSF-1R, maybe you could elaborate a little more on the path forward in new indications there, just some things that you expect to use in combo with the PD-1 agents as has been done by others? Or would you be looking at some other potentially complementary approaches with other therapeutics?

Great. Thanks, Chris. So from the way we're thinking about the feedback we got from FDA, I think it's 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 higher 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're 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, for -- with Chris's question, I just can't go into too much detail on what all those options are, but we're trying to balance all of those various factors. 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're looking at lots of opportunities, as I mentioned in my prepared remarks, the -- there's good preclinical data on, obviously, combination with PD-1 or PD-L1s and then there are other folks doing those experiments. Our understanding is some of the data might now be at SITC from the collaboration between Five Prime and BMS. There's also preclinical data to support combinations with chemotherapy. There's data to support combinations with radiotherapy. There's data to support combinations with cell therapy. And we're doing some preclinical work to see whether the combination might work when we combine it with entinostat. So the -- I guess the challenge here is there's lots of different opportunities, and we want to sort through all of those before me 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.

Our next question comes from Hartaj Singh with Oppenheimer.

So just a question on colorectal cancer. The -- what's interesting to me is that unlike non-small cell lung cancer melanoma, it's less well-developed in the IO area, where there's a lot of activity going on. I mean there's a MEK inhibitor plus, I believe, Roche's PD-L1 would have good Phase II data, and were able to accelerate. Actually, it was earlier than Phase II and accelerated into Phase III 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 I just got a quick question on 2112 after that.

So I think Michael earlier sort of described the type of patients we're enrolling. These are patients who have progressed after standard of care and unfortunately, they're in desperate need of new therapy. We agree with you that the PD-1 alone is again, being careful to limit it to the sort of run-of-the-mill colorectal cancer, the microsatellite stable colorectal cancer, hasn't really been all that promising at all. The combination with a MEK inhibitor did look quite interesting in the early Roche data. And so that's a clue that perhaps our ways, that some of these tumors are immunoresponsive 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'll be both accelerated and full approval paths. Then you said you had a question on 2112?

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 you know the trial is fairly -- has planned for the first-line therapies. Any changes that you see from the new CDK4/6 being approved and does that change anything or not really that's sort of in the protocol and you expect that to just sort of move along?

So I'll let Michael Metzger take that one.

Yes, I -- thanks, Hartaj. I think, look, CDK4/6 inhibitors are kind of going after first-line therapy. And I think, from our perspective, it doesn't really change the dynamic so much. There's utilization, first and second line today but we do take all 3. We're ultimately fighting for first-line therapy. So from our perspective, we're positioning ourselves as 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 your trial and that probably shouldn't change that much even with a new one in the first line, right?

Right. I think -- thanks for clarifying. What we're seeing in our trial, roughly 30% to 50% of our patients will have failed CDK4/6 inhibitors. So most of that is [I brands], 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 that has already gone through CDK4/6, which is of course very important for physicians in terms of their choices of next-line therapy.

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

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, this does conclude today's presentation. You may now disconnect, and have a wonderful day.