Constellation Pharmaceuticals, Inc. (NASDAQ:CNST) Q4 2019 Earnings Conference Call March 10, 2020 5:00 PM ET
Ron Aldridge - Senior Director, Investor Relations
Jigar Raythatha - Chief Executive Officer
Emma Reeve - Chief Financial Officer
Conference Call Participants
Brian Abrahams - RBC
Kripa Devarakonda - SunTrust Robinson Humphrey
Maurice Raycroft - Jefferies
Do Kim - BMO Capital Markets
Mike Ulz - Baird
Marc Frahm - Cowen
Silvan Tuerkcan - Oppenheimer
Ladies and gentlemen, thank you for standing by and welcome to the Constellation Pharmaceuticals Fourth Quarter 2019 Earnings Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] Please be advised that today’s conference is being recorded. [Operator Instructions]
I would now like to hand the conference to your speaker today, Ron Aldridge, Senior Director of Investor Relations at Constellation. Please go ahead, sir.
Thank you, Joel. Good afternoon everyone and welcome to this conference call to discuss Constellation's fourth quarter financial results and operational performance. Participating in our call this afternoon are Jigar Raythatha, Constellation's CEO; and Emma Reeve, our CFO.
Please turn to Slide 2. Before we begin, I want to point out that our presentation today will include forward-looking statements, which are subject to certain risks and uncertainties. Actual results may differ materially due to various important factors, including those described in the Risk Factors section of our most recent Annual Report on Form 10-K filed with Securities and Exchange Commission. This document can be found at the Investors tab of Constellation's website, as well as at the SEC website.
Forward-looking statements represent our views only as of the time of this call and should not be relied upon as representing our views as of any subsequent time. We undertake no obligation to update these statements.
And now, I'll turn over the call to Jigar.
Thank you, Ron and good afternoon everyone. This is our first quarterly earnings call, and I’m excited to tell you about the progress we are making in our programs, and about what we expect to achieve for the remainder of 2020.
Please turn to Slide 3. First, I'd like to provide you with some key highlights about Constellation. We have a portfolio of wholly owned clinical programs featuring CPI-0610, which targets the BET family of proteins, and CPI-1205 and CPI-0209, both of which target EZH2.
We believe CPI-0610 has the potential to transform the standard of care in first-line myelofibrosis. And we've also been able to see signals of potential disease modifying effects in second line patients either as a combo therapy or as a monotherapy. In addition, we've been developing CPI-1205 in prostate cancer. We are now fully enrolled in our Phase 2 ProSTAR study and plan to determine next steps later this year.
Moving on to CPI-0209, our second-generation EZH2 inhibitor, this molecule has been designed to engage the target in a different way. We believe this expands the potential opportunity for EZH2 inhibition. Of note, all of our programs were developed from our own discovery platform, which will continue to be a source of innovation at Constellation.
Please turn to Slide 4, please. So, thinking about 2019 as well what's on deck for 2020, 2019 was quite a transformational year for Constellation highlighted by the fact that we generated key proof of concept data for CPI-0610 and presented it at ASCO, EHA and ASH.
Data that we presented at ASH featured CPI-0610's potential ability to provide impact on patients in the second line setting, where we observed signals of CPI-0610's potential benefit in spleen reduction, symptom improvement, hemoglobin increase, and bone marrow fibrosis improvements, both as a combo therapy and as a monotherapy.
We also presented exciting preliminary data from our first line JAK-inhibitor-naive cohorts to patients. In that context, we demonstrated that we were able to achieve SVR35 response rate in 12 out of 15 patients, as well as a TSS50 response in 10 out of 14 patients at the 12-week time point. We also raised capital in 2019 capped off by our public offering in December.
We expanded our portfolio by adding a new molecule into the clinic. As I mentioned, CPI-0209 is a second-generation EZH2 inhibitor. This molecule has been designed to engage with EZH2, not just potently, but very durably as well. These features position us to expand the potential opportunities of EZH2 inhibition.
And lastly, we've expanded our capabilities in the company, particularly in the development organization. And we look forward to continuing to grow the organization in other parameters as well.
Moving on to our 2020 goals, we will begin to build a fully integrated pharmaceutical company. With that in mind, we will further expand our development infrastructure and start to create a commercial organization. We plan to begin a Phase 3 study for CPI-0610 in first-line MF. We will continue to generate meaningful data for other programs as well.
We anticipate that our next data cut will enable us to make a go/no-go decision for CPI-1205 in prostate cancer. And we also expect to establish the recommended Phase 2 dose for CPI-0209 later this year. Finally, we aim to advance our preclinical pipeline and identify novel candidates that may progress into the clinic over time.
Please turn to Slide 5. I'd like to provide a more detailed update on CPI-0610. Enrollment for this program remains on track. We are excited about the preliminary data that we presented at ASH in December of 2019. In JAK-inhibitor-naive patients, we showed significant spleen and symptom response rates.
We also presented additional data in our second line cohorts, where we saw signals of not only spleen in symptom benefits, but also potential disease modifying effects, including increases in hemoglobin and bone marrow fibrosis improvements.
We plan to present additional data at the European Hematology Association Meeting in Frankfurt in June of this year. We plan to present 24-week data in 25 to 30 JAK-inhibitor-naive patients, as well as 24-week data in 70 to 80 second-line patients, including additional data on CPI-0610 as a monotherapy.
Next, I'd like to highlight that we have decided to expand Cohort 1A, our monotherapy cohort in transfusion-dependent patients. We will now enroll up to 60 patients. This is similar to the expansion that we made in Cohort 2A in transfusion-dependent second-line patients for CPI-0610 was added to Rux.
In both cases, the expansion was based on meeting a pre-specified activity threshold in our protocol, specifically at least two conversions out of the first 16 transfusion dependent patients to achieve transfusion independence.
And if you recall that we previously expanded Arm 3, our JAK-inhibitor-naive patients as well. These expansions reflect our continued enthusiasm regarding the potential of this product candidate.
We are also pleased to announce that we received orphan drug designation for CPI-0610 in the United States and in Europe. In both markets, the emphasis of orphan drug designation is on demonstrating the scientific rationale for the treatment on the prevalence of the disease. In the EU, in addition to these two criteria, the condition must also be life threatening or seriously debilitating and there must be either no satisfactory method of diagnosis, prevention or treatment or the new product must be of significant benefit over existing treatment.
We look forward to discussions our CPI-0610 with regulatory agencies in the coming year. These discussions will help refine our plans for a potential registration path for CPI-0610, including our plan to initiate a global randomized Phase 3 clinical trial of CPI-0610 plus ruxolitinib in JAK-inhibitor-naive patients in the third quarter of 2020.
Finally, planning is well under way on the randomized Phase 3 trial for CPI-0610 in first-line myelofibrosis, which is again, is slated to begin in the third quarter of 2020.
On Slide 6, I'd like to show you our currently proposed clinical trial design. We proposed studying the first-line patient population, defined as JAK-inhibitor-naive in either primary MF or MF that progresses from the essential thrombocythemia or polycythemia vera. Patients would then be randomized to either CPI-0610 plus ruxolitinib or placebo plus ruxolitinib in a blinded fashion.
We proposed that the primary endpoint for the study would be shrinkage in spleen of 35% or more at 24 weeks. In addition, 50% reduction in TSS scores at 24 weeks would be a secondary endpoint. We will discuss this proposed design during meetings with regulatory authorities.
Please turn to Slide 7. Finally, I'd like to highlight potential opportunity for CPI-0610. We believe that there are about 40,000 patients who are diagnosed with MF worldwide. About two-thirds of them are at intermediate high-risk. We estimate about half of these patients actually start ruxolitinib, and at some at some point, many of these patients will likely reduce their dose or stop ruxolitinib altogether.
Based on the data that we have generated to-date, we believe that the addressable market for CPI-0610, if approved, could be roughly the current patient population taking ruxolitinib. We would envision that many of these patients, who are currently starting ruxolitinib, could start with CPI-0610 plus Rux.
We also believe that if the exciting data that we have been developing continues to hold, both from an efficacy and a safety perspective, there could be an opportunity to expand the treatable population to include patients that don't start ruxolitinib, because of concerns around anemia.
We also aim to treat patients who stopped ruxolitinib with CPI-0610 as monotherapy. So, with that in mind, we believe CPI-0610 could become part of the new standard of care in MF and potentially expand the overall opportunity.
Now, please turn to Slide 8. Let's discuss our EZH2 franchise. EZH2 is a histone methyltransferase. Its role is to trimethylate H3 K27, and thereby suppress gene transcription. Cancers have found a number of different ways to utilize EZH2, including synergy with oncogenic drivers like androgen receptor signaling in prostate cancer.
EZH2 is also mutated in diseases like lymphoma, and there are a number of different ways that EZH2 can impact solid tumors, including tumor immunity, drug resistance and synthetic lethality. We believe that CPI-1205's properties are desirable in the context, where patients may be hypersensitive to EZH2 inhibition, such as in combination with androgen receptor signaling inhibitors in prostate cancer.
However, in some additional context that we'd like to pursue, including larger solid tumor patient populations, we may require much more comprehensive EZH2 target engagement, not just potently, but durably over time. And this is how we've designed CPI-0209, as our second-generation EZH2 inhibitor.
Please turn to Slide 9. So, turning specifically to CPI-1205, I'd like to – the focus is to overcome resistance to androgen receptor signaling inhibitors such as abiraterone or enzalutamide with EZH2 inhibition. We previously presented data from our Phase 1b study at AACR in 2019 that showed signals of activity with CPI-1205 in patients who were treated in combination with either abiraterone or enzalutamide in a second-line setting.
What we saw was bifurcated response rates. Generally patients either had deep responses with trends towards durability or rapid progression. So, in our Phase 2 trial, we are particularly interested in the measures of durability, such as time to progression and radiographic progression-free survival. As I mentioned, enrollment in that study is now complete. Over the next few months, we will take a data cut, analyze the data and make a go/no-go decision on moving CPI-1205 into Phase 3. A clear signal will be required to move forward.
Please turn to Slide 10. So, moving on to CPI-0209, we believe that this molecule has the potential to be a best-in-class EZH2 inhibitor. As I mentioned, CPI-0209 was designed to be a potent, but also a durable inhibitor of EZH2. In fact, when CPI-0209 binds EZH2 in a biochemical assay, it doesn't come off for months. And with that in mind, we believe that this molecule has the potential to extract the full potential of EZH2 biology. This could allow us to expand into different patient populations that may not be accessible with first generation EZH2 inhibitors.
We are currently assessing CPI-0209 in a Phase 1 dose escalation study. We expect to establish a recommended Phase 2 dose sometime in the second half of the year, and we will then target to begin our Phase 2 expansion cohorts shortly thereafter. Some of the context we are exploring include biomarker-driven strategies, such as the assessment of mutations like ARID1A. We'll further elucidate the development plan around CPI-0209 as we determine the recommended Phase 2 dose.
Please turn to Slide 11. Finally, I'd like to summarize some milestones that we anticipate in the rest of 2020. First, we plan to have an important update for CPI-0610 at EHA. As we discussed earlier, this will include 24-week data on 25 to 30 patients in first-line and 70 to 80 patients in second-line. We also plan to start our Phase 3 clinical trial with CPI-0610 in the third quarter of 2020, and provide a further update by the end of the year.
We also aim to provide an update on CPI-1205, including our decision on next steps for the program in the mid-year timeframe. We anticipate providing an update on CPI-0209 in the second half of the year, primarily focused around establishing a recommended Phase 2 dose.
And now, Emma will discuss our financial results and cash position and runway. Emma?
Thank you, Jigar and good afternoon everybody. So, we had a net loss of $24.2 million or $0.69 per share in the fourth quarter of 2019 and of $85.6 million or $3.04 per share for the full-year, in line with our expectations. Included in those results were stock-based compensation of $1.9 million in the fourth quarter and $6.9 million for the full-year.
Our cash, cash equivalents, and marketable securities as of year-end were $383.9 million. Sufficient, we believe to fund our operations into the second half of 2022. We plan to use these resources to fund our Phase 3 clinical trial to CPI-0610 and to start building the commercial organization needed to launch CPI-0610. In addition, we have sufficient funds to complete the ongoing Phase 2 clinical trial for CPI-1205 and the Phase 1/2 clinical trial for CPI-0209, as well as to support our discovery and preclinical pipeline of compounds and some general operations.
With that, I'll turn the call back over to Jigar.
Thank you, Emma. We'd like to open up the line to questions. Operator, please open the line.
Thank you. [Operator Instructions] Our first question comes from Brian Abrahams with RBC. Your line is now open.
Hi guys, thanks for taking my question and congrats on all the progress. A couple of questions from me, I guess starting off on 610, you mentioned the criteria for expansion of ARM 1A. Bigger picture, I'm wondering, what's the ultimate bar that you see for this expanded study? Are there any endpoints beyond transfusion independent that will be important to look at as well? And then what's your latest feedback from regulators and/or KOLs as to whether or not this arm or even the combination arm could be potentially – the data could potentially enable accelerated approval in this more refractory unmet need population? And I have a follow-up. Thanks.
Okay. Yes, thanks, Brian for the question. I think that's a really important kind of question to think about the relapsed refractory context of MF. And I think maybe just reflecting a little bit on the dearth of novel products being approved in the post-JAK-inhibitor context really points to the fact that novel strategies endpoints may be needed. And in fact, it's not necessarily mechanisms that are missing that could provide benefit to these patients, but rather novel endpoints that allow us to assess the benefits in these patients.
And specifically, spleen and symptoms both have short comings in that refractory or second-line patient population. And so, we realized that early on as a limitation and therefore prospectively stratified our cohorts to be able to assess a novel endpoint that would be in fact a hard endpoint, that could be referred to, and something that we know is a major problem for these patients, as well as something that doesn't improve, kind of naturally on its own with standard of care, in fact may be getting worse, as a result, of standard of care.
So, with that in mind, we are exploring the possibility by expanding these cohorts. It gives us the ability to generate the data to really, and to ask the question, and that's really kind of the goal of why we're expanding these cohorts.
Our view is that, simply showing an erythroid response on its own may not be sufficient, and that's not necessarily with any direct feedback from regulators, but really kind of our own assessments of what is needed based on patient unmet need, discussions with KOLs and the like. And so it's simply kind of showing an erythroid response would not be enough, but really impacting the quality of the patient's life, the potential impact on the health system and then you combine that with – in the form transfusion independence, and then you combine that with true hard measures of improvement in myelofibrosis, including spleen and symptoms, but also disease modifying effects like bone marrow fibrosis improvement and heme function improvement, starts to form a pretty compelling package.
Now, just having said all of that, using transfusion-dependent conversion in myelofibrosis does not have precedent. The transfusions do seem to be something that regulators are becoming more interested in other hematologic context, and so we're really giving ourselves a chance to have that discussion.
Got it. That's really helpful. And then, just one more from me, you laid out the potential addressable market in myelofibrosis. I'm curious, and I know it's obviously very early to think about pricing, but as you think about sort of value proposition, what kind of efficacy do you think you would need to show to potentially enable pricing comparable to the existing therapy? Is that how you're thinking about the future market opportunity here from a revenue standpoint? Or as an add-on, as you described could go much more broadly, might you have a different set of sensitivities and pricing flexibility there? Thanks.
Yes, thank you. I think it's a little early for us to comment on pricing. It's certainly something that we will be assessing pretty closely as the program continues to develop, but, I think you're right. I think it's really going to be dependent on how much impact we're having on these patients that could ultimately drive that kind of decision, and where that all shakes out.
Understood, thanks again.
Thank you. Our next question comes from Kripa Devarakonda with SunTrust Robinson Humphrey. Your line is now open.
Hi, guys. Thank you so much for taking my question and congrats on all the progress. Earlier in one of your presentations, you've mentioned that you plan to expand the first-line cohort in MANIFEST trial to about a 100 patients as well. Assuming that, that is the case, would – is there a potential of accelerated approval in front-line from this expanded cohort? And if that's possible, can you walk us through how you're thinking about it ahead of your discussions with the agency? And also is – the meeting that you plan to have with the FDA, is that a gating factor for your initiation of the Phase 3 trial in third quarter? Thank you so much.
Yes, maybe I'll take the last one first, since that's pretty straightforward I think. I mean, yes, we need to review the kind of the overall design and assumptions that we're making for the Phase 3 trial before we start. And so that will be something that we plan to do over the course of the first half of this year. And that will enable us to begin enrolling patients in the Phase 3 sometime in the third quarter. But as I mentioned, we've been parallel processing the start up of that study and are well under way to get that Phase 3 up and running in that Q3 timeframe.
With regard to the potential for Arm 3 to generate an accelerated approval, again, maybe it's similar to the answer I gave to Brian around this transfusion dependence path, I think what we've done here is given ourselves a chance to have that discussion with – going into this trial, if we saw response rates that were significantly north of what we think is achievable with ruxolitinib, we think that gives us the opportunity at least to have that discussion, and we didn't think that 40 patients would be sufficient to be able to have that discussion, and having upwards approaching a 100 patients could potentially be the basis for trying to pursue something like that.
Again, not a lot of precedent for that path. There have been some analysis scenarios more recently, where there seems to be some traction. And so, we'll just take that as it comes and put ourselves in the best position possible.
Great, thank you. And I have a quick follow-up question. You talked about the potential to expand ruxolitinib opportunity, especially in the patients that don't get on drugs, because they might have anemia. Is there any active thought process in the way you're designing your pivotal trial, so the pivotal patient population is representative of such an expansion?
Yes, I think there is no – the label of Rux actually doesn't include – exclude these patients, right. So, I think it's more just a kind of just general practice where physicians know that there is the potential for hemoglobin levels to drop, while they take JAK-inhibitor therapy and so try to resist using it until they have to particularly in anemic patients. And so that is, the thinking is that if we capitalize on the progress toward effects that we're seeing from CPI-0610 that may be driven by kind of bone marrow fibrosis and improved myeloid biology in the bone marrow compartment, that could be a driver to allow physicians to feel more comfortable putting patients on Rux, knowing that they have something that might counteract the potential toxicity that are associated JAK-inhibition, as well as help to further improve the foundational bone marrow compartment.
Great. Thank you so much. I appreciate you taking my questions.
Thank you. Our next question comes from Anupam Rama with J. P. Morgan. Your line is now open.
Yes, hey guys, thanks for taking our question. This is Matt on for Anupam tonight. So, just one from us, which is we've been thinking about the potential commercial opportunity for 610 across the various lines of myelofibrosis treatment. But in particular in the front-line setting, and I think you alluded to it on Slide 7, but it seems like there is going to be a pretty big potential to expand treatment duration growth on the front-end and back-end, and from the work we've done, it seems like in anemia is the key factor there. So, just wondering if that's in line with your thinking? And if to the extent that you're able to quantify, by how much you might be able to extend the treatment over the current standard of care, that would be super helpful. Thanks so much.
Yes. So, thanks a lot. I think that's a very kind of insightful point. It is precisely kind of avoiding discontinuations as a result of anemia, but also not just that, it's also kind of the improvements that are being sustained on the disease itself, and they're going to keep coming back to, we've gotten accustomed to looking at spleen and symptoms at the data points, which are the gateway from a regulatory pathway perspective. But what we think we're achieving with 610 is far more foundational than that.
And we started to see some of those data through the images that we've shown in the past about bone marrow fibrosis changes. We hope to supplement that with additional data around kind of mechanism about how that's translating into kind of the cellularity of bone marrow, within the bone marrow, that's driving to these effects.
And so hopefully it's not just [stating] off anemia, but it's also driving to an improvement and a reversal of fibrosis and normalization of myeloid biology in these patients that also lead to a longer duration of treatment. And precisely how long that can last it's, I don't think we have enough information to really quantify that.
Some of the patients that we've been treating in the second-line cohorts have now been on for several years. Some of these patients were transfusion dependent and had pretty short life expectancy. And so, that's pretty comforting that it could potentially extend durability for quite some time, but more to learn as we continue to treat these patients.
Yes, awesome. Looking forward to the updates in the rest of the year. Thanks guys.
Okay. Thanks, Matt.
Thank you. Our next question comes from Maurice Raycroft with Jefferies. Your line is now open.
Hi, everyone. Congrats on the progress and thanks for taking my questions. So, it sounds like you're going to get clarity on whether the single arm 100 patients in Arm 3 could serve as a registrational study in the mid-year discussion with regulators. So, I'm just clarifying, will a registrational path in the second-line based on the Arm 2 expansion also be discussed as well in your meeting?
Yes, I mean, specifically, I mean there's multiple components to the various discussions that we'll be having. We'll be looking first for guidance and buy-in on the design of our randomized Phase 3, but as part of some of those discussions and additional discussions, we'll also review all of the data that we've compiled to-date across Arms 1, 2 and 3, and kind of understand what the agency's thinking is on potential paths forward using the endpoints that we design there.
Got it, okay. And just a quick follow-up on 0209. I'm just wondering if you've enrolled any patients with the ARID1A mutation and what the frequency of that is, and then if you could talk about some of the combo options that you would consider with 0209?
Yes, so the dose escalation portion of our 0209 study is all-comers. ARID1A is a mutation that is frequently found in cancer. It's one of the most frequent mutations actually in all of the cancer. And so, while we haven't kind of described anything about the patients that we've enrolled in those studies just yet, and we're still kind of learning about that, it wouldn't be surprising if we happen to find some ARID1A patients, but we're not necessarily skewing the Phase 1 portion of the study to specifically enrich for that specific mutation.
It is of high interest to us, of course, in our expansion cohorts and we've already identified with some preclinical results that bladder cancer in the context of ARID1A mutation is very interesting to us, and that would likely be one of the expansion cohorts that we would pursue. And we're still deciding on what the various other expansion cohorts would be for 0209. And we'll provide more information on that once we've established the recommended Phase 2 dose.
Got it. Thank you very much.
Thank you. Our next question comes from Do Kim with BMO Capital Markets. Your line is now open.
Hi, thanks for taking my question. First on 610, I wanted to go back to the enrollment criteria for the first-line patients. You changed that toward the beginning and allowed patients that did not have anemia, I was wondering if you are noticing any other differences and baseline characteristics for those patients enrolled later in the first-line cohort arm, maybe they had less severe disease, and whether you think that could have an impact on the outcomes?
Yes, I think, I mean, look I think we did liberalize the enrollment criteria from our original criteria for Arm 3. It was originally designed to enroll anemic patients only. After we started to see some of the effects, there was a lot of enthusiasm from investigators to treat patients who were not anemic at baseline, and so we did go ahead and open that up to the traditional kind of essentially what's part of the label population for JAK-inhibitor therapy.
So, we – I'm not sure that there should be any major differences that you should be thinking about relative to baseline characteristics, I mean, we're not – I don't think we are, or physicians are trying to hand-pick patients that would respond better. I mean these are kind of the reflective patients out there that are seeking therapy, and if anything, these are patients who have the choice of going on a standard of care therapy, that shown survival benefit, but rather are seeking an experimental clinical trial.
So, if anything is likely something that's driving that makes them to be less well and perhaps more sick, but overall, as you kind of scan down the various inclusion criteria, nothing has popped out to us as being correlative with response. We've seen kind of responsiveness across a range of different parameters, things that you look at for baseline characteristics, and we'll continue to assess that with more data and more patients. I think that will become increasingly clear to everybody.
Great. Thanks, Jigar. And for 1205, when you make that go/no-go decision, what would a clear signal look like? What's the hurdle in TTP and are there other biomarkers or measures that will factor into your decision?
Yes. And I think that, it's safe to [indiscernible] the prostate cancer is a really dynamically evolving area. We've got the AR agents are all [indiscernible] it out to move upstream and some of them kind of end up being used in the first-line metastatic and then that defines what you would then be used with in second-line. And so that's all kind of a dynamic evolving landscape.
You also have PARP inhibitors, checkpoint inhibitors and chemo, also being studied in various context in that second-line setting. And so we'll be looking at kind of historical data, as benchmarks, as well as our own control arms that we've built into the study, as well as kind of evolving data from competitors to make that decision. So it's not – it's a multi-factorial type of decision for us.
Just as we went into this, we were looking for a clear separation for instance in the 1205 with enzalutamide arm, where we randomized enzalutamide, I think the first order would be that we want to see a clear separation that is significant from enzalutamide, but then also reflecting on historical data that were subsequently published after we started the study shows, clinical time to progression is on the order of two to three months in these patients.
And so, showing a significant improvement over that would be something that we're shooting for. And then I think we also want to assess some of the latest data that have been published around some of these other classes of therapies that I've mentioned to assess kind of what the path forward could be for EZH2 inhibitor in prostate cancer.
Okay, great. And if you don't continue development with 1205, would it be reasonable to think that you will pursue 209 in prostate cancer first, since you have all this experience?
It's possible. I think the trial that we set up here is extremely rich with data. I mean, we'll have well over 100 patients, including very deep translational work. One of the things that we're really proud about is the investment that we've made to learn about various biomarkers and mutations that we think could be interesting for us to follow. And so if we had, hypothetically, a signal that was intriguing, but not very clear in terms of the 1205 standpoint, we could take all those learnings and apply those to 0209 as a hypothetical. And so, we haven't yet decided to do anything like that, but we haven't ruled it out.
Okay, thanks. Thanks for taking my questions.
Thank you, Do.
Thank you. Our next question comes from Mike Ulz with Baird. Your line is now open.
Hi, guys. Thanks for taking the question and congrats on all the progress as well.
Maybe just another 610 question for you in the MANIFEST study and particularly in front-line patients here, maybe you can just talk about the current status of enrollment versus your target of 100 patients? And just maybe how that's tracked versus your expectations? And I'm just curious, if there was any uptick post the ASH data? Thanks.
Yes. Well, I think generally, there was a lot of excitement and enthusiasm post ASH, and even pre-ASH there was from the investigators who were aware of the data, there was a lot of excitement, but as we made it public, there has been certainly, I think a lot more enthusiasm more broadly. I think, maybe, all I can say really on enrollment is that, we're really pleased and it's meeting our expectations.
Got it. And then, maybe just a quick follow-up on 209. So maybe you can talk about some other potential expansion cohorts? You mentioned maybe bladder, potentially prostate, maybe some others that you might be considering or how many you are considering? Thanks.
There are several opportunities we think, kind of move into both indications that are well known for EZH2, as well as things that have not yet been considered among the various EZH2 inhibitors that are in the clinic. And we haven't finalized our decisions on which expansion cohorts we're going to pursue.
So, we'll largely be driven by kind of strategic considerations around things like utilizing the infrastructure that we've built in various contexts, and also to really test the potential of a best-in-class EZH2 inhibitor, which we hope your CPI-0209 is, and make some bold bets that really expand the opportunity, but beyond that, we're not quite ready to kind of disclose any more details about which cohorts.
Got it. Thanks again.
Thank you. Our next question comes from Marc Frahm with Cowen. Your line is now open.
Hi, yes. Thanks for taking my question. First, just with the update that you're planning to give at EHA, I understand we'll get the 24-week on, I guess, the patients we've already seen, and the people that were already in the baseline characteristics. But you've already been enrolling more patients that presumably some of them will have hit the time points you've presented on before, like week 12 and places like that. Should we expect to see any of that data at EHA as well, just earlier time points?
So, earlier than the 24-week data?
Yes, I think, I know we've shared that in the past and it's reasonable to assume that that could be a possibility. We haven't yet decided exactly what data will be presented at EHA. We do know that 25 to 30 patients will have crossed the 24-week threshold. We think that's a really important time point based on kind of its importance from a regulatory perspective. And certainly I think if there is important data out there that would kind of inform how the drug is behaving. We feel like that it will be important to get that out there. So, we'll kind of assess to see what's meaningful, what's different and share everything with you that we think falls into that category.
Okay. And then maybe just on the prior questions about enrollment and given in 2019, you're able to show that this combination was – can be dosed safely in terms of platelet counts and maybe even has benefits on anemia as well. Has that changed enthusiasm within the populations as to whose enrolling at all? I would think that would lead to more people with baseline anemia and more people with baseline low platelet counts wanting to be on the trial, but have you seen that?
Yes, I mean, again, there hasn't been any bias toward a selection of patients with any particular baseline characteristic. So, I think we've set certain minimum enrollment criteria for platelets, for example. And as long as patients qualify they welcome to enroll and we wouldn't stop that. And so there hasn't been any – I wouldn't necessarily point to any specific kind of trend one way or the other, with regard to that.
Okay, great. And then one last one, EZH2 franchise, Jigar, you touched on this a minute ago, I guess, if you had an intermediate result from ProSTAR that maybe you could still pursue it with – follow-up with 1205 – I’m sorry, with 0209 given the proposed benefits, but also if you – even if you see a clear signal, if at that point, you have a recommended Phase 2 dose, that looks safe and everything with 0209, given the proposed benefit, would you still move forward with 1205 in that setting? Or would you then also look to pivot to use have 0209, given the proposed benefits of that molecule?
I think we just have to wait and see what the data [having data shake out]. I mean, if we're ready to move into a Phase 3 that's still substantially further along the 0209, and so I think it just depends on how exciting the results are to make that determination.
Okay, alright. Thank you.
Thank you. [Operator Instructions] Our next question comes from Silvan Tuerkcan with Oppenheimer. Your line is now open.
Thanks for taking my question and congrats on the quarter. I just have a quick one and I have a follow-up. As you expanded the front-line cohort, did you add additional sites or centers that are enrolling patients and where do see data that you have from these additional sites?
Sorry, can you repeat your question, Silvan.
Will you – did you – when you expand the front-line myelofibrosis cohort, did you add additional sites or did you just expand the number in existing sites? And if there are new sites, will we see data at EHA from these additional sites?
Presumably, you'll see data from sites that haven't – we've been, it's the kind of site kind of activation is more of rolling kind of thing. I mean we've been activating new sites from the beginning of study and have many sites and we'll continue to kind of activate new sites. And so that’s necessarily linked to the expansion, but more just kind of how we are aiming to kind of progress with the development of this molecule in the current study, as well as the next study, that we do.
So, with that, with kind of more sites coming on board, there will definitely be an increasing proportion of patients that are coming from more and more sites. The early patients were not all coming for instance from one site, they already represented a pretty diverse array of sites that we're already active.
Alright, great. And then, I think I'm still probably a little bit confused about, could you share with us the discussion how they exactly work with the regulators? What's similar between U.S. and EU? What are some of the differences? And kind of what is your baseline expectations in terms of the outcome for front-line? Is that they would just approve the trial as you presented it today on Slide 5, I believe or 6, or and what is kind of like your baseline case for the second-line indications, what do you think accelerate approval or not or another Phase 3 for the second-line? Thanks.
Okay. Yes, so maybe I'll start with the question that you asked about kind of differences between kind of U.S. and Europe. I mean, I think it's, maybe the first thing I'll say is that the Phase 3 that we've designed is meant to address the requirements for approval globally. And we'll certainly want to confirm that assumption as we meet with regulators outside the U.S., but we believe that, that should be the case.
So, I think stepping back from that, I think, generally kind of in drug development, as you know in Europe there tends to be a less of a likelihood to achieve kind of approvals based on surrogate endpoints and kind of randomized studies are much more meaningful. And so, I mean, if you're asking me what we expect, we expect that continuing to be the case in this context as well.
Having said that, there seems to be a bit more harmonization lately between kind of U.S. and ex-U.S. regulatory authorities, and we'll seek to kind of have those understanding discussions around that as well.
So, but kind of again, just to kind of sum up, randomized Phase 3 is meant to be the basis for full approval. And if there are accelerated strategies to pursue, we'll bring those discussions up and see if they hold, we think that there's at least potential to discuss those possibilities based on all three of our arms. And again, as I mentioned earlier, there's not more information that we have currently about whether or not we think that's likely or not. So, we're just putting ourselves in a position to have those discussions.
Great, thanks. Thanks for taking my questions.
You're welcome, Silvan.
Thank you. I'm not showing any further questions at this time. I would now like to turn the call back over to Jigar Raythatha for any closing remarks.
Okay. I just wanted to say thank you to everybody for joining our call. We really appreciate all of the interest in the company, as well as the support that's been provided to us, and we look forward to providing you an update on our first quarter conference call in mid-May.
Ladies and gentlemen, this concludes today’s conference call. Thank you for participating you may now disconnect.