Good afternoon, ladies and gentlemen, and welcome to the Syndax's First Quarter 2019 Financial Results Conference Call. At this time, all participants are in listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time. I would now like to turn the call over to your host, Ms. Melissa Forst with Argo Partners.
Please go ahead.
Thank you, operator. Welcome and thank you to those of you joining us today for Syndax's Q1 2019 financial results conference call. Joining us this afternoon for prepared remarks will be Doctor. Brakes Morrison, Chief Executive Officer Michael Metzger, President and Chief Operating Officer and Rick Shea, Chief Financial Officer. And also joining us on today's call for the question and answer session will be Doctor.
Michael Myers, Chief Medical Officer and Doctor. 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 would ask you to please turn to the 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 factors, including those discussed in the Risk Factors section of the company's most recent quarterly report on Forms 10Q as well as other reports filed with the SEC. Any forward looking statements represent the company's views as of today, May 6, 2019, only. A replay of this call will be available on the company's website, www.syndax.com, following the call. And with that, I'm pleased to turn the call over to Doctor. Briggs Morrison, Chief Executive Officer of Syndax.
Thank you very much, Melissa, and thank you to everyone for joining on today's call and on the webcast. Slide 3 provides a high level summary of our current corporate priorities. As we progress through this year, we continue to focus our resources on 2 incredibly exciting opportunities. The first is we are anticipating a positive readout of E2112, our Phase 3 trial of entinostat in hormone receptor positive breast cancer and the subsequent filing of our first NDA and the corresponding launch of our first product. I want to again emphasize that a positive overall survival trial in hormone receptor positive HER2 negative breast cancer would be a landmark result and will be transformative for Syndax, its shareholders, but most importantly for patients.
We believe the entinostat opportunity in hormone receptor positive breast cancer carries blockbuster potential. The E2112 Data Safety and Monitoring Committee recently completed their scheduled 2nd quarter interim analysis and has informed us that the trial will continue as planned. This result is encouraging and consistent with our base case assumption. We will now turn our attention to the upcoming Q4 2019 analysis. I'd also like to take a moment to congratulate Doctor.
Rosheen Connolly on behalf of everyone here at Syndax for winning the ECOG Akron Young Investigator Award this past Friday. As you may know, Rosheen is the lead investigator for E2112 and we appreciate all the work that she's done to make E2112 a successful endeavor. 2nd, we remain on track to file an IND this quarter for SNDX-five thousand six hundred and thirteen, our potential first and best in class menin targeted agent for the treatment of mixed lineage leukemias, followed by the rapid initiation of our broad clinical program in acute leukemia. As we continue to learn more about the potential of 5,613 in acute leukemia, we see this molecule becoming another important value driver for our company. We believe that the breadth of indications we will investigate with 5,613 represents a second blockbuster opportunity.
Now let me review these opportunities in a little more detail. Slide 4 summarizes the design of our Phase 3 trial of entinostat in hormone receptor positive HER2 negative breast cancer. The trial has randomized 608 patients to either exemestane plus placebo versus exemestane plus entinostat and the focus of this trial is now clearly on overall survival. As we've noted before, overall survival interim analyses are conducted approximately every 6 months and 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 breakthrough therapy designation in data The Data Safety and Monitoring Committee recently informed us that based upon the Q2 interim analysis, the trial passed a formal futility analysis and continue as planned. I'd like to remind everyone that each interim analysis evaluates both the possibility that the trial is futile through a formal futility analysis at each interim as well as the possibility that the trial is positive based on a statistically significant improvement in overall survival.
So we are pleased that the trial has not stopped for futility and we remain confident that the trial will be positive. The final analysis of this trial will be conducted once there are 410 survival events. We don't know when the 410th event will occur, but based upon the modeling we've done, we believe the final analysis could occur in November of this year or possibly in May of 2020. Slide 5 emphasizes the potential for the entinostat exemestane regimen to be the preferred agent after CDK4six therapy for hormone receptor positive HER2 negative breast cancer representing a blockbuster market opportunity. Now that CDK4six therapies, most notably Ibrance are being used increasingly as first line agents, there's a clear unmet need for a therapy that will be effective in patients who have 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 the post CDK4six patient population. This population of patients is substantial with an estimated 34,000 patients each year who go on to receive hormone therapy after failing first line therapy and who could therefore be eligible to receive the entinostat regimen. We're also of course quite excited about the upcoming IND filing for our genetically targeted agent 5,613. Slide 6 shows the similarity between our menin program and other medicines that attack the fusion proteins that are the result of chromosomal rearrangements. The first example of a recurring chromosomal rearrangement in oncology was the so called Philadelphia chromosome, which results in the BCR ABL fusion protein and which led to the development of Gleevec and other BCR ABL inhibitors.
Since then, there have been many examples of medicines that specifically attack fusion proteins that result from a chromosomal translocation, including medicines against EML4 ALK fusions, NTRK fusions and RET fusions. In these chromosomal translocations, there was strong evidence that the resulting fusion protein is driving the cancer cell. And being able to precisely define these patients led to the development of medicines that demonstrate large treatment effects in specific patient populations and enabled a rapid clinical development and regulatory path. I want to emphasize that our 5,613 program is an example of a targeted therapy that was designed based upon our understanding of a specific chromosomal rearrangement that leads to a specific fusion protein known to drive the leukemic process. On Slide 7, we summarize the status of this program.
The IND is on track to be filed later this quarter with the Phase onetwo clinical program to begin soon thereafter. Once the IND is approved, we'll be able to provide the final details of our Phase onetwo clinical program. However, we can say that our goal is to enroll adults with MLLr leukemias followed by children with MLLr leukemias. And we also intend to enroll adults with NPM1 mutant leukemia based upon the very compelling preclinical data that was presented at ASH this past December, which showed that 5,613 has promising activity in that disease as well. Again, I want to emphasize that we see a rapid and straightforward clinical development path for 5,613 similar to the path taken for patients with TRK fusions or IDH1 mutations.
We expect that the molecule should have single agent activity and it's quite possible that we could observe clinical activity early in the clinical development path, again, unlocking significant near term value for Syndax. As we continue to learn more about the potential of 5,613 in acute leukemia, we see this molecule becoming an additional and an important value driver. Let me now briefly return to our entinostat ENCORE clinical program in which we evaluated entinostat in combination with PD-one pathway antagonist. I will remind investors that the ENCORE program was set up as a signal seeking program exploring multiple tumor types with different immunologic characteristics. We also look for biomarkers that could predict clinical benefit.
Slide 8 shows that the immunologic environment is quite variable in different tumor types. The ENCORE results to date indicate that the beneficial effect of entinostat is strongly evident in inflamed tumors, but not in the other immunologic settings. So we believe this is an important conclusion of our work. Slide 9 summarizes our findings recently at AACR. Consistent with prior data, we see a strong signal of clinical benefit when entinostat is combined with KEYTRUDA in patients with non small cell lung cancer, the disease has progressed after both chemotherapy and a PD-one antagonist.
We've also identified a biomarker peripheral blood classical monocytes that appears to predict clinical benefit in this population of patients. In addition, we've seen a strong and durable clinical benefit when entinostat is combined with KEYTRUDA in patients with melanoma whose disease has progressed on both a PD-one inhibitor and a CTLA-four inhibitor. We're especially encouraged by the positive feedback we've received from therapeutic area experts and investigators who like us recognize the potential of this combination to deliver a clinically meaningful benefit to patients who currently lack alternative options. As we discussed on our last quarterly call, following the availability of positive E-two twelve OS results, we will determine whether to advance the entinostat PD-one combination program into 1 or more registration trials. Let me now turn to Slide 10 and SNDX-six thousand three hundred and fifty two, our potential best in class monoclonal antibody targeting the CSF1 receptor.
We initiated a trial testing 6,352 in chronic graft versus host disease in the Q4 of last year. Chronic graft versus host disease is a frequent complication of hematopoietic stem cell transplantation, wherein the donor derived immune cells contribute to the initiation and development of fibrosis and manifestations of many of the advanced disease symptoms. In preclinical models, blockage of the CSF1 pathway with anti CSF1R antibodies can result in the depletion of donor macrophages, thereby preventing and reducing chronic graft versus host disease. We believe that chronic graft versus host disease represents an attractive opportunity and we look forward to sharing initial efficacy data in the second half of this year. Finally, Slide 11 summarizes how the many transactions that we've completed to acquire both 6,352 and the menin MLR programs prove that we have an ability to strategically expand our pipeline.
Our management team and Board have established relationships that allow us to identify quality, differentiated assets and the extensive clinical development experience of our team gives us a competitive advantage in closing agreements. We continue to expand significant effort in this area and we consider this capability to be a core strength of our company. I'd like to now turn the call over to Michael Metzger, our President and Chief Operating Officer to discuss our recent financing. Michael?
Thank you, Briggs. As summarized on Slide 12, we completed an important equity financing on March 29, raising $27,500,000 in new capital. This financing sets us up for success over the next 12 to 18 months and accomplishes 3 important goals for Syndax. First, as Rick will detail in his remarks, the financing extends our cash runway, enabling us to operate well beyond critical program milestones for entinostat and hormone receptor positive metastatic breast cancer and proof of concept in the 5,613 program. 2nd, we structured the financing at a significant premium to market and through the warrant structure set up the opportunity to raise additional capital as our stock price appreciates.
This creative structure served to limit the amount of dilution to our existing shareholders at a time when we believe our stock is undervalued. And 3rd, this offering gave us the opportunity to add top quartile investors to our list of significant shareholders. We are quite thoughtful about how we build our shareholder base and we are delighted to have new shareholders who are aligned with our vision for building long term value. I will now turn the call over to Rick to review our financial results. Rick?
Thank you, Michael. Results of our operations for Q1 2019 and the comparison to the prior year period are included in our press release, so I won't repeat them in these remarks. Additional financial details will be available in our quarterly report on Form 10 Q, which we intend to file later this week. Turning to Slide 13, we ended the Q1 of 2019 with $92,700,000 in cash and 31,600,000 shares outstanding. The net change in cash for Q1 was an increase of $11,800,000 The operating cash burn of $16,400,000 was more than offset by $27,400,000 of net proceeds from the offering and $800,000 of net proceeds from our ATM.
Looking ahead, I'd like to provide updated financial guidance for both Q2 and for the full year 2019. For the Q2 of 2019, we expect R and D expenses to be $9,000,000 to $10,000,000 and total operating expenses to be $13,000,000 to $14,000,000 including approximately $1,500,000 of non cash stock compensation expense. For the full year 2019, our guidance is unchanged. We expect R and D expenses of $46,000,000 to $50,000,000 and total operating expenses of $60,000,000 to $64,000,000 Operating expenses for 2019 are expected to include non cash stock compensation expense of $6,000,000 and offset by interest income of approximately $2,000,000 So our net cash burn for 2019 is expected to be $52,000,000 to $56,000,000 So our current cash, along with this reduced spending, will allow us to operate the company to achieve key milestones for our prioritized programs, specifically OS results for E2112 an early proof of concept for our targeted menin inhibitor. Now I'd like to turn the call back over to Briggs.
Thanks very much, Rick. To close our call with a clear summary of our company priorities, we believe that a positive OS result in E2112 would be transformative for Syndax and create significant shareholder value. Although the final OS readout for E2112 could occur by the end of this year, we are prepared for a potential later final readout in mid-twenty 20. We also are very excited about the prospects for 5,613, our menin MLLr inhibitor. We expect that the molecule could have single agent activity and it's quite possible we could observe clinical activity early in the clinical development path, again unlocking significant near term value for Syndax.
We remain excited about our data in non small cell lung cancer and melanoma as recently presented at AACR. Nonetheless, we believe it was prudent to pause our further development spending in IO until such time that we receive recommended Phase 2 dose in solid tumors at the end of this quarter and anticipate having initial efficacy in chronic graft versus host disease later in the year. Finally, we continue to look for molecules or technologies to bring into our portfolio. We have a proven track record of delivering on this pillar of our strategy and I believe this is a core strength of our company. As always, I'd like to thank the team here at Syndax, our collaborators and most importantly, the patients, trial sites and investigators involved with our clinical programs.
With that, I'd like to open the call for questions.
Our first question comes from the line of Bert Hazlett from BTIG. Your line is
I have 2. First on the menin MLLr program. There was some discussions at AACR with regard to differentiation syndrome that was seen with many of the AML therapies and maybe that that was an unrecognized or under recognized phenomenon with many of those therapies. Would you expect to see differentiation syndrome early on with the menin program you have? And if so, can that be considered maybe an on target AE for the program?
What's your second question, Bert?
2nd question is regarding the biomarker activity of entinostat. Is there an ability to translate the biomarker that you've selected for non small cell lung cancer in melanoma?
Okay. So I'll take the first one and I'll turn over to Peter Ordemlich to take the second one. So the differentiation syndrome, so again, if we look at the biology of what we think is is happening when we treat leukemic cells with the MLLr inhibitor, you do turn off expression of genes involved in leukemogenesis and the cells are believed to differentiate before they die. So it wouldn't shock us if we saw some evidence of the differentiation syndrome that you see with IDH inhibitors and others. Whether that is any kind of surrogate for efficacy, I'm not so sure.
I think we would much rather rely upon the accepted regulatory endpoint of complete responses. And I'll turn your second question over to Peter, if you want to just comment Peter about the I think Bert's question is around the monocytes and its applicability to melanoma.
Yes. Hi. The short answer is, yes, we see similar trends in the baseline monocytes in terms of response prediction in the melanoma cohort as we do in the lung cohort.
And if you just as a follow-up, if you choose to continue these programs, would you expect to enrich in some way based on that biomarker in melanoma?
Bert, this is Briggs. I'll take that. So I don't think we've made that decision yet. That was obviously part of the reason we were letting the melanoma data mature a bit further, both so that we could better characterize the durability and that we could characterize the potential of using monocytes or other biomarkers. So, it's certainly something that is a consideration, but until we decide whether to go forward with either one of those programs, We probably don't have to say too much about exactly what the details would be of that program, but it is a consideration.
Okay. Thank you.
Our next question comes from the line of Madhu Kumar from R. W. Baird. Your line is open.
Hey, guys. Thanks for taking my question. So first one is, when we're looking back at ENCORE-three zero one and looking at the protocol, it appears that the protocol allows patients who are on entinostat plus exemestane to continue on drug through progression as a maintenance therapy, while patients who progressed in the control arm had to come off therapy and go on to standard of care. Is that the case? And if so, what fraction of patients in the entinostat arm stayed on entinostat therapy post progression?
So your question Madhu is about ENCORE 301? Yes. Yes. I don't know, Peter, do you know the answer to that question?
All patients came off at the time of progression. I don't nobody who has continued on the entinostat after disease progression.
Okay, great. And then when you guys think about ENCORE-three zero one in terms of the entinostat to the exemethane placebo arm, How do you think about that arm's performance relative to other exemestane placebo arms and other clinical trials? And kind of how do you reconcile the performance of that arm in ENCORE 301 versus, for example, bolero 2 and other exemestane kind of monotherapy clinical trials?
Yes. Peter, do you want to take that one too?
Sure. Thank you. It's a good question and we thought about that quite a bit as we got our data and the BALERA-two data read out and a few other trials of the exemestane. It wasn't too far off if using the I think it was the investigator assessed or the central assessed boleroTE, I can't quite remember right now. But the differences between what we had for our control arm and what that exemestane control arm read out were not that different in terms of magnitude.
So the investigators we spoke to at the time were not very much concerned by that. And in fact, based on the fact that you recall in 301, we were enrolling patients actively progressing on their prior non steroidal aromatase inhibitor. So the thought was that those tended to be more perhaps resistant to their aromatase inhibitor activity. So overall, the investigators were not very surprised at what we had for the median outcome. I can't really comment on sort of the more recent trials where exemestane had read out as a control arm, just the patient populations may have shifted a bit.
But at least at that time, there really wasn't much concern that ours was underperforming that significantly.
Okay, great. If I can squeeze one more in. So thinking about the menin MLL inhibitor, so now that the kind of IND filing and the kind of clinical trial plan is pretty well formed, what do you guys think is the best PD biomarker for showing inhibition of the MEN and MLL interaction?
Yes. So Madhu, I don't think we've said much about the PD assays. We're working diligently on those as I sort of answered to Bert's question. I think to be candid, the thing that would get us most excited is to see clinical complete responses.
Our next question comes from the line of Chris Shibutani from Cowen.
Thank you very much. With 5,613, it is obviously one of the molecules that's going to go into the clinic. And I think there are several of the compounds or at least one that is in the clinic as well. Can you help us think about how we should think about potentially differentiating either the compounds themselves or the approach that you're taking, would be helpful for context? Thank you.
Yes, thanks a lot, Chris. So I think at this point in time, it's a little hard to put too much to say too much the differentiation. I assume the molecule you're referring to is Kira's molecule. We know that they had their IND approved and from what they have said publicly, I believe that their program is probably studying similar populations to the ones we're looking at both MLLr, NPM1 mutants. I think they also said they would do a little broader search maybe in their early program with an all comer population.
But from what we can tell, from what's publicly available, I think their molecule hits the same target that ours does and figuring out exactly what the differentiation is between the 2, I think too early to be able to say because we don't know exactly which molecule they're taking forward. But I would say that at some point it would be great for people to be focused on the differentiation between 2 active agents. So 6 months from now when we have good efficacy data and maybe they also have a little bit that is probably more relevant question.
Great. And then the recent financing that you did, certainly brought on board some smart money on your behalf. Can you talk about how confident you feel about your current plan in the event that, for instance, the E2112 does not read out until mid-twenty 20? So if you feel the need to perhaps once again make other considerations, because I noticed that you also did talk about continuing to be on the search on a business development environment. It would be helpful to understand in the event we get out to mid-twenty 20 for a review out there?
Thank you.
Yes, Chris, it's Rick Given the guidance that we've provided for cash burn in 2019, we should end 2019 with cash in the low to mid $50,000,000 range without doing anything further, which at that time would give us slightly more than a year's worth of cash prospectively. So given an E2112 timeframe of probably Q2 2020, we should be in pretty good shape to have a result and to still have a reasonable amount of cash. But certainly, it will be something that we'll have to pay close attention to at the time.
Great. Thanks. We look forward to getting an update with you guys at ASCO. Thank you.
Thanks, Chris. Our next question comes from the line of Christopher Marai from Nomura Instinet. Your line is open.
Hey, good afternoon. Thanks for
taking the question. Maybe first question just on entinostat and assuming success, I was wondering if you could delineate for us some of the plans you've made with respect to commercialization for the compound and from this point and then future points what the plans would be to continue to progress commercialization? And then secondly, with respect to that in different geographies, would you be open to potentially partnering the asset? Can you walk us through some of your thought processes there around commercialization? And then one follow-up, if I may.
Thank you.
So Chris, let me let Michael Metzger take that question.
Yes. Hey, Chris.
So in terms of commercialization, I think we've been pretty open about the fact that we've had discussions over time with potential partners to optimize the opportunity for the drug, which as you know is a global launch. And our reach probably doesn't extend outside of the U. S. In terms of our own commercial aspirations, but we do have aspirations to potentially launch the drug either on our own or in partnership with a large pharma in the U. S.
As well. So we have opportunities. I think partners are as we are waiting eagerly for the data to emerge and at that time we think we'll have multiple opportunities to partner either regionally or globally. And in terms of what our work is internally has been so far, I mean, we're not we have not undertaken to build a sales force as of yet. I think small company like Syndax typically waits a little bit longer to hire a field force.
So that's not something we've done. Clearly, it's not forecast in our burn. We have done some pre commercialization work as you would expect. And I think we're well prepared on that front to take the next step when the data comes in and we'll update everybody at that point.
Want to comment on geography?
Yes. And so I think the comment about geographies, as I said, we are interested most interested in launching and being represented meaningfully in terms of sales and marketing in the U. S. And then certainly we have partners in Japan and Korea and China now, but the rest of the geographies are open. And so, we would be potentially open to a partnership outside the U.
S. Or also in some part globally where they would take all the other geographies including part of the U. S. And help us there as well. So we have, as I said, some options to flex depending on how we make out.
Thanks, Michael. Just with respect to that, maybe could you further elaborate on aspirations to have your own sales force? I mean, obviously, if you have success with Menin down the road, it could be advantageous, obviously, different indications. So how should we be thinking about that? And how is Syndax thinking about that?
Yes, I know it's
a great question. I think if we're fortunate enough to have, breast cancer in a portfolio on its own, it's a big indication. Companies have launched in breast cancer, small companies have launched in breast cancer and have grown up through that process, roughly round numbers of 100 reps or so, 150 reps can do well in this indication. And so that's not unattainable for a small company like Syndax. The menin inhibitor, obviously focused on leukemia, but they're all oncologists.
And so there is some overlap there and there's some certain specialists who we would an academic center that we would focus on. So that's probably a smaller need in terms of sales and marketing and headcount to cover the leukemia space. So certainly doable and it would be a great outcome if we had both drugs to promote in one bag. And so we'll be actively thinking about that when the time comes, certainly something we aspire
to. Got it. Thank you. And then with respect to menin, just a follow-up on a few of the other questions. It sounds like we're looking for the next data set to include response rate data?
And then, if that's correct, could you maybe remind me about roughly how many patients we might see in that first clinical update once you get that in the clinic and things rolling? Thank you very much.
Yes. So Chris, let me just comment on that. Until the IND is accepted and we know exactly what the Phase 1 or 2 program looks like, I think we'd rather hold off on giving too much. We just can't really say very much about how many patients and when and things like that. So we will say much more about that once the IND is accepted and we know exactly what the FDA has agreed to in terms of our clinical
program. Got it. Thank you so much.
Our next question comes from the line of David Lebowitz from Morgan Stanley. Your line is open.
Hi, this is Ishmael on for David. Thank you for taking our question. Piggybacking on the IND for 5,613, can you just give some guidance on when we should expect to hear more strategies on the monotherapy versus the combination opportunities? And more specifically, considering the mechanism for the menin inhibitor, which combinations would be logical to consider? Thanks.
Sure. So I think, the obviously the IND is filed really just on the monotherapy and I think what we'll be able to convey in more detail after the IND is accepted is what the initial program would be in monotherapy. There's a variety of different combinations that could make sense and that we're thinking about and exploring, but I don't think we'll be in a position to say much more about the combination program till probably a little further down the line.
Okay, thanks for the color. And separately for the Phase 1 for 6,352, the data presented in the second half, can you remind us what type of efficacy data we should expect to see from the study? Thank you.
Sure. So again, just to clarify, I don't know that we've specifically said we'll have a scientific presentation of data. The trial is set up as a dose escalation trial in patients with GVHD. So it's a combination of both getting safety and efficacy. There'll be small numbers of patients and we're using the sort of accepted chronic graft versus host disease efficacy or Michael, you can comment on what the tool we use for assessing efficacy.
Yes. It's a standard tool used to assess GvHD. It's not at all associated with any tumor type or basic anticancer response. It's specifically geared to GvHD patients And it's based on multi organ systematic responses based on consensus instrument.
Okay.
Okay, great. Thank you.
Our next question comes from the line of Harshita Palishetty from B. Riley FBR. Your line is open.
Hey, good afternoon, everyone. Just one question for me. With regard to your menin inhibitor in MLL and NPM1 mutant leukemias, you've indicated that you're targeting patients who have failed initial therapies. So I was hoping you could provide some additional color on what the initial induction therapy is for these patients? I mean, I think you have previously mentioned that these patients are treated with essentially first line options for AML or ALL, but the challenge is that they obviously don't respond well.
So any additional info on what the response rate and duration of response looks like for these patient subsets in first line would be helpful. Thank you.
Hi, Harshita. Thanks so much for your question. So just to clarify, so all of these patients are treated with conventional therapy today. The practicing physicians will generally know who their MLLr patients are and their NPM1 mutant patients are both from standard chromosomal analyses and from sequencing. And so they will receive standard induction therapy and for the most part go into remission just as would any patient, newly diagnosed patients with one of these diseases.
The main challenge is that they have a high relapse rate. And so we would anticipate, again, we'll have more details once we have the IND approved, but we would anticipate treating patients who have failed standard therapy or therapies. And again, that is a little bit of a moving target of course. There are new agents being tested in both ALL and AML. So exactly what regimens patients have previously had and failed before they come on to our trials, I think we'll be able to say more about that once the IND is approved.
Great. Thank you, Briggs. That's helpful.
Our next question comes from the line of Joel Beatty from Citi. Your line is open.
Hi, thanks for taking the questions. The first one is on Phase 3 breast cancer trial for entinostat. Could you discuss what appears what makes the Q2 'twenty analysis definitely the final analysis? Is there potential that it could go past that or is it in the protocol that that will be the last analysis?
Right. So Joel, where the protocol specifies is the final analysis for the trial is when there are 410 events. So the final analysis is based is an event driven analysis. Based upon our modeling of when we think the 410th event would occur, that's where we say it could be as early as the end of this year or it could be in the spring of next year. So it's not the protocol doesn't specify a time that the trial will be analyzed, it specifies the number of events.
So it's just a question of how long it takes for the 4 10 events to accrue.
Got it. Thanks. And another question on the trial. Could you discuss the bar set for the futility analyses and then also the alpha that's been spent so far and what remains for the remaining overall survival analyses? Thanks.
Yes. So I don't think there's a publication that describes the overall design of the trial and the statistics that went into the trial, but I don't think in that publication they specifically describe the rules around futility. So I'm not sure that that's in the public domain. There you can imagine some of the standard rules that people use. If at any point the hypothesized hazard ratio is below the 95% comps and all the point estimate, some people use that as evidence that you're not going to ever achieve a positive trial.
But I don't think the formal rules have been described in the public domain for this trial. So I think the I forgot your second part of your question.
I think you answered the futility part and then also on the alpha spend so far and what remains?
So the alpha spend overall for all of the interim analyses doesn't add up to very much. I don't know that we've ever described exactly how much is spent at each interim analysis, but if you go through all of those and you have to go to the final four 10 events, it's a relatively modest amount of alpha spent.
All right, got it. Thank you.
We have no further questions at this time. I will now turn the call back to Doctor. Morrison.
Great. Well, thank you everybody for joining the call. Thank you for all of your questions. We assume we'll meet up with many of you in Chicago later this month. And again, if you have any other questions along the