Good day, ladies and gentlemen, and welcome to Syndax Third Quarter 2018 As a reminder, this conference may be recorded. I would now like to introduce your host for today's conference, Melissa Forst of Argo Partners. Please begin.
Thank you, operator. Welcome and thank you to everyone who's joining us on the line and the webcast this afternoon for a review of Syndax's Q3 financial and operating results. I'm Melissa Force with Argo Partners. And with me this afternoon is Doctor. Briggs Morrison, Chief Executive Officer and Rick Shea, Chief Financial Officer.
And joining during the question and answer 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, factors, including those discussed in the Risk Factors section in the company's most recent quarterly report on Form 10 Q as well as other reports filed with the SEC.
Any forward looking statements represent the company's views as of today, November 5, 2018 only. A replay of the call will be available on the company's website atsyndex.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 Q3 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 the 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 3 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-six zero two and six zero three, exploring the combination of entinostat and a PD-one pathway antagonist in triple negative breast and ovarian cancer. Both ENCORE-six zero two and six zero three are randomized placebo controlled trials, which allow very straightforward interpretation of trial results.
If either is positive, that would represent 1 of the first randomized trials to validate a novel mechanism that adds to the efficacy of a PD-one pathway antagonist. We anticipate having early clinical data from our chronic graft versus host disease trial with SNDX-six thousand three hundred and fifty two. And finally, we are on track to file the IND and start clinical trials for our menin inhibitor, which we have now named SNDX-five thousand six hundred and thirteen. As we continue to learn more about the potential of SNDX-five thousand six hundred and thirteen in acute leukemia, we see this molecule becoming an additional and important value driver for our company. So again, 2019 is shaping up to be a very significant year for Syndax.
Let me now turn to Slide 5 and give you an update on our Phase 3 trial of atinostat in hormone receptor positive HER2 negative breast cancer. Slide 5 again summarizes the trial design. The trial has now randomized 608 patients to exemestane plus placebo versus exemestane plus entinostat, and the focus of this trial is now clearly and unequivocally on overall survival. As we've noted before, overall survival interim analyses are done approximately every 6 months. So the next interim OS analyses will be around May November of 2019.
Positive outcome at any of the OS interim analyses or upon achieving the final number of events needed to conclude the study would allow us to file for regulatory approval based upon the terms of our special protocol assessment
with the FDA.
We remain very confident in the possibility that E2112 will achieve a survival benefit. Recall that it was the Phase 2 overall survival results that led to the granting of the breakthrough therapy designation by FDA. And as I summarized on our call on October 25, based upon the results of the Phase 2 trial combined with the statistical design of E2112, we've always believed that the OS endpoint was more likely to be positive than the PFS endpoint in 2,112. Hence, the fact that PFS did not achieve the very high statistical hurdle of a p value of 0.002 does not in any way diminish our confidence in the possibility of achieving a survival benefit in E2112. We also know that overall survival is the most valued endpoint for patients, for physicians, for regulators and for payers, and hence a positive OS trial would enable both rapid regulatory view in the U.
S. And in Europe and potentially rapid payer access. Slide 6 again emphasizes potential for the entinista exemestane regimen to be the preferred agent after a CDK4six therapy for HER2 positive for HR positive breast cancer. We know that CDK4six therapies, most notably Ibrance, are being used increasingly as first line agents, but there's a clear desire to understand what therapies will be effective in a patient who has stopped responding to a CDK4six inhibitor. Our current estimate is that between 30% 50% of patients in E2112 will have received a CDK4six inhibitor prior to entering the trial and thus we will have a highly relevant data set in this population.
This population of patients is relatively large with an estimated 34,000 patients each year who go on to receive hormone therapy after failing first line therapy and could therefore potentially be eligible to receive atinostat. Slide 7 summarizes our ENCORE clinical trial program, which we are testing entinostat in combination with PD-one pathway antagonists, either PD-one antibodies or PD L1 antibody. We've now communicated our plan for non small cell lung cancer and we are continuing to follow patients in the melanoma cohort of ENCORE 6 1. Our randomized placebo controlled trials in triple negative in ovarian cancer are fully enrolled as is our single arm colorectal cancer trial with readouts anticipated in the first half of next year for all three indications. We've previously communicated as we complete our initial clinical trials in each tumor type, we will prioritize which indications to advance to registration trials based upon a combination of unmet medical need, the competitive landscape and our ability to generate an attractive return on our investment.
Taking those factors into account, we announced that we are moving forward with a biomarker based registration trial in non small cell lung cancer patients whose disease has progressed after both platinum based combination chemotherapy and a PD-one antagonist. Slide 8 summarizes the emerging area of clear unmet medical need for patients with non small cell lung cancer whose tumors have progressed after both a platinum based combination chemo and PD-one antagonist. Slide 8 also points out that the use of biomarkers for selecting patients for appropriate therapy is common practice today in non small cell lung cancer. Assuming a positive outcome from our focused biomarker driven trial, which we are now calling ENCORE 6 7, we believe the novel biomarker we are evaluating could transition easily into this treatment landscape. Turning to Slide 9, I'd like to briefly again review ENCORE 607, the registration trial we designed for entinostat KEYTRUDA combination based on discussions with non small cell lung cancer experts as well as input from the FDA.
To enroll in this study, patients must have received a platinum doublet based chemotherapy and pembrolizumab. Pembrolizumab must be their immediate last therapy before entering the trial. We anticipate that the majority of patients will have received the triplet of pembrolizumab, pemetrexate and cisplatin, the regimen used in KEYNOTE-one hundred and eighty nine and will have progressed while on maintenance pembrolizumab. Patients will also be allowed to enter if they have received platinum based chemotherapy first line treatment followed by pembrolizumab second line. We will first assess the level of classical monocytes in the peripheral blood using a validated assay.
Patients with low monocytes will be treated with entinostat plus KEYTRUDA. Those with high monocytes will be randomized to be treated with standard of care chemotherapy of the investigators choice versus the entinostat, KEYTRUDA combination. Following discussions with FDA, the primary endpoint of the trial is PFS based upon the PFS data we saw in Phase 2. Let me again call out 2 key points about this focused biomarker driven trial. The trial is designed both to validate the classical monocyte biomarker and to demonstrate that the combination therapy of entinostat plus KEYTRUDA is superior to standard of care chemotherapy in the high monocyte population.
The trial will enroll approximately 180 patients with data potentially available within 2 years, second half of twenty twenty. This could position us to be the 1st novel therapy with regulatory approval both in the U. S. And EU in this sizable population of lung cancer patients. Slide 10 summarizes the study designs for ENCORE 602 and 603.
ENCORE 602 is our Phase II trial exploring the combination of entinostat with atezolizumab in triple negative breast cancer in patients who have received at least 1, but no more than 2 prior lines of therapy. And ENCORE 603 is our Phase 2 trial exploring the combination of entinostat with avelumab in ovarian cancer for patients who have received at least 3, but no more than 6 lines of prior therapy, including at least one course of platinum based therapy. Both ENCORE-six zero two and six zero three are randomized placebo controlled trials, which allows very straightforward interpretation of trial results. And we anticipate results from ENCORE 603 in the Q1 of 2019, results from ENCORE 602 in the IO combination trials over the next points across our ENCORE IO combination trials over the next month. Again, as we complete our initial clinical trials in each tumor type, we will prioritize which indications to advance to registration trials based upon unmet need, the competitive landscape and our ability to generate an attractive return on our investment.
We've already announced that we will go forward a registration trial in non small cell lung cancer patients whose disease has after both platinum based combination chemotherapy and a PD-one antagonist. We will consider further investments as data matures in our other proof of concept trial. Let me now turn to Slide 12 and SNDX-six thousand three hundred and fifty two, our potential best in class monoclonal antibody therapy targeting the CSF1 receptor. We presented the Phase 1 healthy volunteer data at SIFTE in November of 2017 and the multiple ascending dose study in cancer patients is ongoing as is the combination trial of 6,352 with Imfinzi, AZ's PD L1 inhibitor. We anticipate selecting a recommended Phase 2 dose sometime in the Q2 of 2019.
Our chronic graft versus host disease trial is now underway, and we anticipate data from that trial about a year from now. Last but certainly not least, on Slide 13, I summarize our Mendon MLLr program. As mentioned earlier, we've now selected a development candidate, which we call SNDX-five thousand six hundred and thirteen and remain on track to file an IND in the first half of twenty nineteen. To date, we've generated a significant amount of preclinical evidence suggesting that these molecules can target 2 genetically defined leukemias: the MLL rearranged leukemias and the NPM1 mutant leukemias, which together represent a fairly sizable patient population. We presented exciting positive data at this year's AACR demonstrating efficacy in PDX models of both of these leukemic subsets, and those presentations can be found on our website.
There will also be 2 presentations highlighting our menin MLL program at the ASH Annual Meeting next month, including an overview of the field by Doctor. Scott Armstrong from the Dana Farber and additional data on the role of the menin MLL interaction in NPM1 mutant leukemia. We plan to continue exploring indications where these agents could make an impact, especially focused on settings where menin has been implicated as a driver of disease. I want to emphasize that we see a rapid and straightforward clinical development path for SNDX-five thousand six hundred and thirteen like the path that was taken for patients with TRK fusions or IDH1 mutation. We expect that the molecule should have a single agent activity.
We will of course target patients who have either an MLL rearrangement or NPM1 mutation. These patients are readily identifiable in clinical practice today and present an see this see this molecule becoming an additional and important value driver for our company. And with that, I'll turn it over to Rick for the financial update.
Thank you, Briggs. Turning to Slide 14 for the 3 months ended September 30, 2018, Syndax reported a net loss of $17,300,000 or $0.68 per share compared to $15,100,000 or 0.68 dollars per share for the comparable prior year period. 3rd quarter 2018 research and development expenses increased to $14,100,000 from $12,200,000 for the prior year, an increase of $1,900,000 or 16% due to an increase in development activities of $800,000 and increased employee compensation expense of 1,200,000 dollars 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 a decrease in E2112 costs. The increase in employee compensation costs was primarily due to increased headcount. G and A expenses increased to $4,100,000 during the Q3 of 2018 compared to $3,600,000 for the prior year, an increase of $600,000 or 16%.
The increase was primarily due to an increase in employee related expenses of $300,000 and in professional and legal fees of $200,000 At September 30, 2018, there were 26,100,000 common shares issued and outstanding, which includes the 2,000,000 warrants held by BVF. Syndax ended the Q3 of 2018 with a cash balance of just under $90,000,000 And as we mentioned on our last earnings call in the 3rd quarter, we commenced sales of our stock off 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 Q3, we recorded $9,400,000 in net proceeds from the ATM, which offset our cash burn for the 3rd quarter. We ended the prior quarter with a cash balance of $98,400,000 So the net change in cash for Q3 was a net decrease of $8,800,000 The operating cash burn was $16,100,000 plus there was a decrease in accounts payable of $2,100,000 and that was offset by the $9,400,000 of ATM proceeds.
To date in the Q4, we've recorded an additional $6,100,000 of net proceeds from the ATM, which will offset our Q4 cash burn. Additional financial details will be available on our annual report or our quarterly report, excuse me, on Form 10 Q, which we intend to file today. Looking ahead, I'd like to provide financial guidance for both Q4 2018 and for the full year 2019. For the Q4 of 2018, we expect R and D expenses to be $13,000,000 to $15,000,000 and total operating expenses to be $17,000,000 to $19,000,000 and this includes approximately $1,500,000 of non cash stock compensation expense. So with cash at the end of Q3 just under $90,000,000 and reflecting our Q4 guidance for operating expenses and our actual Q4 to date ATM proceeds and our projected interest income, we expect year end cash to be approximately $80,000,000 For the full year 2019, we expect R and D expenses of $54,000,000 to $58,000,000 and total operating expenses of $68,000,000 to $73,000,000 Operating expenses for 2019 are expected to include non cash stock compensation expense of $6,000,000 So with the clinical programs we're presently conducting and have committed to, we're projecting that our operating expenses for 2019 will be lower than our 2018 operating expenses.
As Briggs mentioned, we believe that we have multiple significant value enhancing development milestones over the next 6 to 12 months. And with a projected year end cash balance of approximately $80,000,000 we will have a solid cash position entering 2019. I'd like to now turn the call back over to Briggs.
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 to summarize 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 timeframe, 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 Our first question comes from Bert Hackett of BTIG. Your line is open.
Thank you, and thank you, Briggs and everybody for the update. 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 have presented 34 patients at ASCO. We have a larger sample size.
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 class of omanocyte also helps us in melanoma.
Okay. Thank you. And then with the MLLr program, again, as you mentioned, an exciting program and it's good to see it move into the clinic. 5,613 seems to be one of the portfolio. Could you discuss in brief characteristics that lifted 5,613 to the top?
And should we think about other 2nd gen compounds that might be active in maybe potential resistant species that arise?
Right. So 5,613 came to the top for the sort of general pharmaceutical properties 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 molecules.
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 molecule seem to it seems to be hard for a cell to escape.
Okay. Thank you. And then just one question with regard to guidance. Does R and D spend, Rick, include any spend on advancement in melanoma? Thanks.
At this time, it does not.
Okay. Thank you for your time. Thanks, Bert.
Thank you. Our next question comes from Chris Shibutani of Cowen. Your line is open.
Thanks very much. 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 3. 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 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 602603 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 2 mutational burden TMB, which went through somewhat of an update at ESMO where the Bristol study went out and it was unclear sort of what path that biomarker was going to continue to move forward. Can you share your own points of views about that particular biomarker and the role that you believe it may play across any of these indications or combination studies that 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 checkpoints, particularly in the lung and melanoma setting, even though we know that our patients have 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 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 exome sequencing a little harder to get off the samples, that data will end up being just by definition a bit 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.
Thanks for 2019. It's helpful to have that, but 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 and A at the lowest possible for 2019 that you spent the max on the R and D and the lowest on the 2 operating expenses, that's not necessarily realistic, but I'm trying to reconcile that with the potential to expand so many clinical programs. I could understand you have this R and D, but can you give us a sense of 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 is slow.
Yes, Chris, I'll take that. So what we have happening in 2019, obviously, the accrual is 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, 602603 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 6,352 program, we actually had some significant manufacturing tech transfer costs that occurred in 2018 that won't be recurring in 2019. We'll just presently at least we just have the GVHD study, which is relatively modest in cost. So the cost overall for that program are actually going to be down year over year. Costs in the minute 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.
Thank you for the additional color.
Thank you. Our next question comes from Christopher Marai of Nomura. Your line is open.
Hey, good afternoon. Thanks for taking the question. 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, we saw early data here at ASH, it was preclinical and you're going to start a trial in the second quarter of 'nineteen. Should we expect any data at ASH 19 on that? And then secondarily, how do you look at the competitive landscape there in terms of both enrolling trials and perhaps IP? There's an IND expected for another similar compound Q1 of 2019 by a competitor. I'm just wondering what your thoughts are around both those IP and potentially a competitive trial enrollment.
Yes. So Chris, I think it's a little early for us to say whether there will 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
that
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 Cura, 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're quite confident that we can find sites that can enroll our trial. And I think you also asked about IP?
Yes. That's correct. Any concerns about freedom to operate or any potential concerns around IP with this compound? And maybe remind us you have composition of matter around them? Thank you.
Yes. So Chris, it's Michael. I don't think there's any concerns about IP. This is 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 because it's brand new IP in terms of expiration. So we're in quite a good spot.
Great. Thank you. And then one quick follow-up just on entinostat. Obviously, at ESMO, we saw some data for another HSTAC and inhibitor in the metastatic breast cancer setting showed a PFS benefit in some emerging OS data. And I was wondering if that's helped inform your view of when we may potentially see the OS read here from your entinostat trial, the ongoing Phase 3?
And if you had any other thoughts having reflected on that data with respect to entinostat's chance for success.
Yes. So obviously, the chitomidecamp, on it's not entinostat, it's a different molecule. It is a Class I selective H stack inhibitor. It does have some both structural and pharmacologic similarities to entinostat. I think our best predictor of how our trial will readout comes primarily from our own Phase 2 data.
I think the fact that the China My team was able to show a PFS benefit that looked very similar to what we saw in our Phase 2 trial with 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.
Understood. Thank you very much. Congrats on the quarter.
Thank you. Our next question comes from Konstantinos Afralakis. Your line is open of JMP Securities.
Thanks very much for taking my questions guys and apologies if any were already addressed in the call. So 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 analysis performed on past clinical trials. Intinostat has an extensive sort of clinical experience. So anything you've gleaned there and an update there? And then a quick follow-up.
Right. So, Constan, we did mention that, as I said, the other place where we're looking at this 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 monocytes is also useful in that population as it turns out 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. In the pivotal trial for non small cell lung, did you was it discussed or have you considered including KEYTRUDA monotherapy cohort in that trial? Or do you not think it's necessary given wanting to validate the biomarker and compare 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 IRB to have a patient who had just progressed on a PD-one then go on to a trial in 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, 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 against standard of care chemotherapy.
All right. Thanks very much, guys, and congrats on the quarter.
Thanks, Tati.
Thank you. Our next question comes from David Lebowitz of Morgan Stanley. Your line is open.
Thank you very much for taking the question. 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 let Michael Myers, our Chief Medical Officer, answer that
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 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 then with respect to the patient, the size of each of the cohorts, was the Phase 2 data the basis for determining the powering in the upcoming NANCE trial?
Roughly, yes, exactly. We were looking to see if we could replicate in a rigorously defined Phase twothree trial the results that we had observed in the Phase II trial.
And with respect to the 60260 3 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-one, PD L1s were chosen for 6 216?
Yes, sure. So I think, David, if you look at our program, it's we tried to set up a 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 and 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 they sort of sit outside the tumor. Ovarian is sometimes referred to as the immunologic desert where you actually don't see a lot of T cells 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 and 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 it how we ended up with the various partners.
Obviously, we're very pleased with all three of our partners. We it's been wonderful partnerships, great scientific collaboration and that's how we ended up where we are.
Thank you very much. And I guess one last question. Could you remind us the threshold for colorectal cancer in the SIMON2 stage?
So yes, so in the SIMON2 stage, we're trying to the hypothetical response rate is 15%. We're trying to exclude a lower bound of 5% in the Simon 2 stage design with a 90 percent power and a Type I 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. Your line is open.
Hi, thank you. Just a quick question for Rick. You said that the ATM you raised $9,400,000 in the 3rd quarter $6,100,000 so far in the 4th quarter. I was just wondering if you can give us the share count associated with those with that monetary value. Thank you.
Yes. Let me see if I have that handy here. Let's see. I have an overall share count, I believe, of 2,100,000 shares for the 15.5 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.
Okay. Thanks, Rick.
Thank you. At this time, I'd like to turn the call back over to Doctor. Boryson 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.