Q4 2019 Earnings Call
Ladies and gentlemen, today's conference is scheduled to begin shortly piece continues to standby. Thank you for your patience.
[music].
Gentlemen, thank you for standing by and welcome to the constellation Pharmaceuticals fourth quarter 2019 earnings Conference call.
At this time, all participants I know listen only mode. After the speaker presentation, there will be a question and answer session.
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I would.
Now I turn the conference your speaker today, Ron Alderidge Senior director of Investor Relations at Constellation. Please go ahead Sir.
Thank you Joe well good afternoon, everyone and welcome to this conference call to discuss constellations fourth quarter financial results and operational performance participating in our called.
Good afternoon art, Jigger, right thoughtful constellations, CEO and am I reading our CFO.
Please turn to slide two.
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.
It's may differ materially due to various important factors, including those described in the risk factor 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 constellations website as well as at the FCC website.
Forward looking statements represent our views only as at the time at this call and should not be relied upon as representing our views as of any subsequent times. We undertake no obligation to update these statements and now I'll turn it over the call to trigger.
Thank you Ron and good afternoon, everyone.
This.
Since our first quarterly earnings call had an excited to tell you about the progress we're making it our programs.
And if so what we expect to achieve for the remainder of Twentytwenty.
Please turn to slide three.
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First I'd like to <unk> I'd like to provide you with some some key highlights about constellation we have a portfolio of wholly owned.
Clinical programs featuring Cpis, there were six Ted which targets the best family of protein and CPR 12, both side, you know two or nine both of which target easy it's too.
We believe Cpis. Your was 610 has the potential to transform the standard of care in first line myelofibrosis.
We've also been see been able to.
Signals a potential disease modifying effects in second line patients either as a combo therapy or as a monotherapy.
In addition, we've been gel being C.P.I. 12 will fight in prostate cancer.
We are now fully enrolled in our phase two prostar studied and plan to determine next steps later this year.
Moving on to C. P I O to O nine or second generation easy. Its two inhibitor. This molecule has been designed to engage the targeting a different way.
We believe this expands the potential opportunity for easy age to inhibition.
Oh, no Oliver programs were developed from our own discovery platform, which will continue to be.
As a source of innovation at constellation.
[laughter] thinking about the please turn to slide four please.
So thinking about 2019 as well it's what's on deck for 2020 2019 was quite a transformational year for constellation highlighted by the fact that we generated keep of concept data.
For Cpis, there was six pen and presented at ASCO.
And ash.
Do you know that we presented at Ash featured Cpis your six tends ability to potential ability to provide an impact on patients in the second line setting where we get deserve signals of Cpis there were six tenths potential benefit in spleen.
Auction symptom improvement hemoglobin hemoglobin increase and bone marrow fibrosis improvement, both as a combo therapy and as a monotherapy.
We also presented exciting preliminary data.
From our first line JAK inhibitor naive cohorts of patients in that context, we demonstrated that we were able to.
She SVR was 35 response rate in 12 out of 15 patients as well as a T.S.S. 50 response intend at a 14 patients after 12 week time point.
We also raised capital 20, and 29 at the end 2019 capped off by our public offering in December.
We expanded our portfolio.
By adding a new molecule into the clinic as I mentioned Cpis. Your 209 is the second generation easy age two inhibitor. This molecule has been designed to engage with each to not just potently, but very durably as well.
These these features position us to expand the potential.
Opportunities of each to 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 and other parameters as well.
Moving onto our 2020 goals, we will begin to build a fully integrated.
Pharmaceutical company with that in mind, we will further expand or development infrastructure and start to create a commercial organization. We plan to begin a phase three study for Cpis. There was six pen in first line M.F., we will continue to generate meaningful data for other programs as well. We anticipate that are next data cut will enable us.
To make and go no go decision for CP I towable five in prostate cancer.
We also expect to establish the recommended phase two dose for Cpis. There are 209 later this year.
Finally, we aim to advance our preclinical pipeline and identify novel candidates that may progress into the clinic overtime.
Please turn to slide five.
I'd like to provide a more detailed update on Cpis Euro 610.
Enrollment for this program remains on track we're excited about the preliminary data that we presented at Ash in December of 2019, and JAK inhibitor naive patients we showed significant spleen and.
Response rates. We also presented additional data in second line in our second line cohorts, where we saw signals of not only spleen and symptom benefits, but also potential disease modifying effects, including increases in hemoglobin and bone marrow fibrosis improvement.
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 82nd line patients, including additional data on Cpis Euro 610, as a monotherapy.
Next I'd like to highlight that we've decided to expand cohort one day or 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 two way in transfusion dependent second line patients for CP I hear a 610 was.
Adam added to rocks in both cases the expansion was based on meeting if you specified activity threshold in our pro 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 armed three.
Jack can never naive patients as well these expansions reflector consistent or continued enthusiasm regarding the potential of this product candidate.
We're also pleased to announce that we received orphaned orphan drug designation for Cpis. There were 610 in the United States and in Europe.
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 care. These two criteria the condition must also be life, threatening or seriously debilitating and there must be either no satisfactory method of diagnosis prevention wood treatment.
Or the new product must be of significant benefit over existing treatment.
We look forward to discussions on Cpis, there were 610 with regulatory agencies in the coming year.
These discussions will help refiner plans for potential for a potential registration path for Cpis. Your was 610, including our plan to an.
She a global randomized phase three clinical trial of Cpis. There were 610, plus ruxolitinib in JAK inhibitor naive patients in the third quarter of Twentytwenty.
Finally planning is well underway on a randomized phase three trial for Cpis. There were 610 in first line myelofibrosis.
Which is again is slated to begin in the.
Third quarter Plenti 20.
On slide six I'd like to show you are currently proposed clinical trial design.
We propose studying.
The first line patient population defined as JAK inhibitor naive in either primary M.F. or M.F. that progress is from essential thrombocythemia or.
Like the me of era.
Patients would then be randomize to either Cpis Euro 610, plus ruxolitinib or placebo plus ruxolitinib in a blinded fashion, we propose that the primary endpoint for the study would be shrinkage in spleen up 35% or more at 24 weeks.
In addition, 50% reduction in T S.
Scores, a 24 weeks would be a secondary endpoint, we will discuss this proposed design during meetings with regulatory authorities.
Please turn to slide seven.
Finally, I'd like to highlight.
[noise] potential opportunity for Cpis. There was 610, we believe that there were about.
40000 patients were diagnosed with M.F. worldwide.
Two thirds of them or intermediate high risk.
We estimate about half of these patients actually start ruxolitinib and.
And at some at some point many these patients will likely reduce their dose or stop ruxolitinib. All together based on available under that when the data that we have generated to date.
Hey, we believe that the addressable market for Cpis. There were 610, if approved could be roughly the current patient population taking ruxolitinib.
We wouldn't division that many of these patients who are currently starting ruxolitinib could start with CPI zero 610, plus rocks. We also believe that it's exciting data that we have we have been.
And continues to hold both from an efficacy and 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 aimed to treat patients who stopped ruxolitinib would cpis. It was 610 as monotherapy so with that in mind, we believe cpis.
As you were 610 could become part of the new standard of care and a map and potentially expand the overall opportunity.
Now please turn to slide eight.
Let's discuss are easy age two franchise.
Easy H. too is the histone methyltransferase its role is to try Messily H. three K 27 and.
Thereby suppressed gene transcription.
Cancers, I found a number of different ways to utilize easy age to including synergy with oncogenic drivers like androgen receptor signaling in prostate cancer.
Easy age two was also mutated and diseases like lymphoma, and there are a number of different ways that he's each to can impact.
Solid tumors, including tumor immunity drug resistance and synthetically Dallas.
We believe its <unk> five properties are desirable in the context, where patients maybe hyper sensitive easy to inhibition such as in combination with androgen receptor signaling amateurs in prostate cancer.
However in some additional.
<unk> in context that we'd like to pursue including larger solid tumor patient populations. We may require much more comprehensive easy age to target engagement, not just potently, but durably overtime.
And this is how we've designed to Cpis. Your Jews you were nine as our second generation use each two inhibitor.
Please turn to slide.
Slide nine.
So turning specifically to C.P.I. 12 of five I'd like to fill the focus is to overcome resistance to androgen receptor signaling inhibitors, such as abiraterone or enzalutamide.
With easy age to inhibition.
We previously presented data from our phase one de study at.
C. R 2019 that showed signals of activity with Cpis level five in patients were treated in combination with either abiraterone or enzalutamide side in a second line setting.
What we saw was a bifurcated response rates generally patient either had deep responses with trends towards to.
Ability or rapid progression.
No wonder a phase two 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.
It could go no go decision and moving C.B. I told the five into phase three a clear signal will be required to move forward.
Please turn to slide 10.
So moving on to Cpis era to zero nine we believe that this molecule has the potential to be a best in class each two inhibitor as I mentioned <unk>.
As you choose your nine was designed to be a potent but also a durable inhibitors each too in fact when cpis. There are two with your nine binds DCH tuna biochemical last say it doesn't come off for a month.
And with that in mind, we believe it this molecule has the potential to extract the full potential that easy age to biology.
This could allow us to expand into different patient populations that may not be accessible with first generation easy to inhibitors.
We're currently assessing Cpis your Jews Eurnine in phase one in a phase one dose escalation study.
We expect to establishing recommended phase two dose sometime in the second half a year and we will then.
Then target to begin or phase two expansion cohorts shortly thereafter.
Some of the contracts. We are exploring include biomarker driven strategies, such as the assessment that mutations like everyone else.
We will further elucidate the development plan around Cpis. There are 209 as we determine the recommended phase two dose.
Please turn.
On to slide 11.
Finally, I'd like to summarize some milestones that we anticipate in the rest of 2021st we plan to have an important update for Cpis. There was 610 at as we discussed earlier. This will include 24 week data on 25 to 30 patients.
In first in first line and 70 to 80 patients in second line.
We also plan to start or our phase three clinical trial with Cpis zero 610 in the third quarter of Twentytwenty and provided further update by the end of the year.
We also aimed to provide an update on CP October five including our decision.
Our next steps for that program in the mid year timeframe.
We anticipate providing an update on cpis. There are 209 in the second half of the are primarily focused around establishing a recommended phase two dose.
And now ammo will discuss our financial results and cap position and runway Emma.
Thank you Jessica and good afternoon everybody.
So we had a net loss of $24.2 million, Oh, 69 cents a share in the fourth quarter, that's 29 team.
I live of $85.6 million, all $3.04 per share for the full year in.
Aligned with our expectation.
Included in those results with stock based compensation of $1.9 million in the fourth quarter and $6.9 million for the full year.
Okay cash equivalents, a marketable securities as of yearend with 383.9.
$10 million.
Sufficient we believe to fund our operations into the second half of 2022.
We plan to use these resources to from the phase three clinical trial to see PEO 610 and to start building the commercial organization needed to launch Cpis 610.
In addition, we have sufficient funds to complete the ongoing phase two clinical trial for Cpis 12 of five and the phase one two clinical trial for CP <unk> to nine.
Well as to support our discovery I'm pleased preclinical pipeline of compounds and some general operations.
With that.
I'll turn the call back over to chicken.
Thank you Emma we'd like to open up the line to Ah two questions. Operator, Please open the line.
Thank you as a reminder to ask a question you want me to press Star one on your telephone.
To withdraw your question press the pound key please standby well be compile the <unk>.
Ross there.
Our first question comes from Brian Abrahams with RBC. Your line is now open.
Hey, guys. Thanks for taking my question and congrats on all the progress example of course, I mean, I guess starting off on on 610, you mentioned the criteria for expansion of a of arm one a.
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 vendor pay wells as to whether or not disarm or even the comedy.
Nation arm.
Could be a.
It could potentially a data can potentially enable accelerated approval and this.
More refractory on Monday population.
Thanks.
Okay, Yes Ah. Thanks, Thanks, I think frankly the question I think that's a it's a really important.
Okay.
Turning to think about the open or relapsed refractory context, it up enough and I think I think maybe just reflecting a little bit on the dearth of of novel products being approved.
In the post JAK inhibitor, a context really points to the fact that novel novel strategies endpoints or maybe needed in fact, it's not necessarily.
Ali.
Mechanisms that are that are missing that could provide benefit these patients, but rather a novel endpoints that allow us to assess the benefits in these patients.
And specifically spleen and symptoms both have shortcomings.
In that refractory ore second line patients.
Relation and so so we we realize that early on as the limitation and therefore.
Prospectively stratified or cohorts to be able to assess a novel endpoint that would be in fact, a hard endpoint.
That that could be referred to.
Something that we know is a major problem for these patients.
As well as you know something that doesn't improve I'm going to naturally on its own with standard of care in fact, maybe getting worse as a result of standard of care.
So so without mine, we are exploring the possibility.
By expanding these cohorts and gives us.
The ability to generate the data to really kind of asked the question and that's really kind of the goal of a why we're expanding these cohorts.
Our view is it simply showing an earthquake response on its own you know may not be sufficient and that's not necessarily with any direct feedback.
You know from.
New leaders, but really kind of our own assessments of what is and a needed based on connotation unmet needs discussions with K wells and the like and so simply kind of show being in a risk right response.
I would not be enough, but really impacting.
The quality of the patients life the.
And in fact in the health system, and then you combine that with you know in the form transfusion independence.
And then you combine that with true kind of 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 fund a pretty compelling.
Package now just having said all of that.
Using transfusion dependent conversion in myelofibrosis does not have precedent you know, but transfusions do seem to be something that regulators are becoming more interested in other hematologic context, and so we're really giving our chance or sell the chance to have that discussion.
Got it that's really helpful. And then just just one more for me you.
Laid out the potential addressable market.
In Myelofibrosis I'm curious 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 a pricing comparable to the existing therapy is that how you're thinking about kind of the future market opportunity here from a revenue standpoint or as an add on that 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 it's a little early for us to comment on pricing. It's certainly something that we will be assessing pretty 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 are having on these patients.
That could that could ultimately drive a dry.
That that kind of decision or whether it'll shakes out.
Obviously, the thanks again.
Thank you.
Next question comes from crap that deliver a condo with Suntrust Robinson Humphrey Your line is open.
Hey, guys. Thank you so much for taking my question and congrats.
That's an all the progress.
Oh, yeah in one of your presentations you'd mentioned that you plan to expand the first line cohort in manifest trials to about 200 patients as well.
I'm, assuming that that is the case would is that a potential off accelerated approval in.
French line from this extended cohort and if that's possible can you walk us through how you're thinking about it I had to all I'm your discussions with the agency and not to is the at the meeting that you plan to have the FDA is that deciding factor.
The initiation off the PC trials in third quarter.
Thank you so much.
Yeah, maybe I'll just take the last one first sunset that's pretty straight forward I think yeah. I mean, yes, we beat we need to review the I'm going to the overall design and assumptions that were making.
For the phase three 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 three sometime in the third quarter, but as I mentioned, we've been parallel processing processes.
During the startup of though that study and are well underway to get that phase three up and running in that Q3 timeframe with regard to the or the potential for armed three to generate a accelerated approval you know again.
Maybe it's similar to the answer I gave to Brian around you know this transfusion dependent Pat you know I think what we what we've done here is given ourselves the chance to have that discussion.
You know with the going into this trial. If we saw response rates that were you know significantly north of what we think is achievable with ruxolitinib.
Yep.
We think that gives us the opportunity to these type of that discussion and we didn't think that 40 patients would be sufficient that'd be able to have that discussion and having upwards you know approaching 100 patients.
Could potentially be have a basis for trying to pursue something like that but again not a lot of precedent for that.
That path there have been some analogy scenarios more recently, where there seems to be some traction and so we'll just trying to take that as it comes and put ourselves in the best position possible.
Thank you and I have a quick follow up question you talked about the potential two weeks and Ruxolitinib.
To de especially in the patients that don't get on drugs, because they couldn't they might have anemia.
But is there any active I'm talking processing.
The way you're designing your pivot to the trial. So we don't pivot to patient population is representative of such an expansion.
Yeah, I think there's no though the label of Rotce actually doesn't include exclude these patients right. So I think it's more just a.
Kind of just general kind of practice, where.
You know physicians know that there's the potential for hemoglobin levels to drop 'em, while they take JAK inhibitor.
To be and so I'm trying to.
You know resisting using it until they have to particularly in anemic patients.
And and so so that he is a thinking is that if we you know capitalize on the can a pro risk right effects that we're seeing from Cpis. There was 610 the maybe.
Driven by kind of bone marrow fibrosis and improved.
And as my way biology in the bone marrow compartment, you know that could be a driver to allow.
Physicians to feel more comfortable putting patients on rocks, knowing that they have something that might counteract.
The the butter.
Central toxicities ever so she would JAK inhibition as well as help to further improve the foundational kind of bone marrow compartment.
Great. Thank you so much I appreciate you taking my question.
Our next question comes from.
Well with JP Morgan Your line is now open.
Yeah, Hey, guys. Thanks for taking our question. This is not entre and pumps night, just one from US which is you know we've been thinking about the potential commercial opportunity for 610 across the various lines of mountain fibrosis treatment, but in particular into frontline setting and I think you alluded to it on slide seven but it seems like.
There's going to be it pretty big potential to expand treatment duration, both on the frontend and backend and from the work we've done it seems like in EMEA is a key factor there.
So just wondering if that's in line whats your thinking and as 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.
Super helpful. Thanks, so much.
Yeah. So so thanks. Thanks, a lot I think that's that's a very kind of insightful point, what is precisely kind of avoiding gonna discontinuations as a result of in any of it but also not just that is also going to the.
That are being sustained I'm on the disease itself and they got to keep coming back to you know we've gotten accustomed to looking at spleen and symptoms ATCA 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.
The data through the images them shown during the past about bone marrow fibrosis changes, we hope to supplement that with additional data around kind of mechanism about how how that's translating into kind of the cellular parity or bono.
Within the bone marrow, that's driving to these effects and so hopefully.
It's not just eating off anemia, but it's also driving to a I'm an improvement and a reversal of fibrosis and normalization of my way biology. In these patients that also lead to a a longer duration of ups treatment and precisely how long that can.
I.
And last it.
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 are they were transfusion dependent and had pretty short life expectancy and so so that's pretty comforting that that it could potentially.
Extender ability for quite some time, but but more to learn.
As we continue to to treat these patients.
Yeah, awesome looking forward to any update or in the rest of the year. Thanks guys. Okay.
Thanks, Matt.
Thank you. Our next question comes from Widebody aircraft with Jefferies. Your line is now open.
Hi, everyone. Congrats on the progress and thanks for taking my questions I'm. So it sounds like you're going to get clarity on whether the single arm 100 patients and armed three could serve as a registrational study in the mid year discussion with regulators. So I'm just clarifying a will a registrational path in the second line based on our two.
Based on the arms you expansion also be discussed as well and your meeting.
Yeah, I mean, I mean, specifically I mean, there's multiple components to the various discussions that will be having we'll be looking first for kind of.
Guidance and buy in under design of our randomized phase three.
But but as part of.
Some of those discussions in additional discussions will also review all the data that we've compiled the date across arms, one two and three and and kind of understand what the agencies.
Thinking is on quite a potential paths forward using the the endpoints that we design.
And there.
[laughter].
Got it Okay, and just a quick follow up on Oh, two Onein I'm just wondering if you back if you've been rolled any patients with the Eric one a mutation and what the frequency of that is and then if you talk about some of the combo option, so you'd consider with or without you on that.
Yes, so the or the <unk> the dose escalation portion of our O'toole nine study is all commerce.
Everyone. A is a is the mutation that is.
Frequently found in cancer, it's one of the most frequent mutations actually in all of cancer and so.
While we.
Haven't tried to describe kind of anything about the patient they'd be rolled in those studies just yet we're still going to learning about that it wouldn't be surprising if we happen to find some every 20 patients, but we're not necessarily skewing. The phase one portion of the study specifically enrich enrich for that specific mutation. It is of high interest to us of course.
First in our expansion cohorts and we've already identified with some preclinical results that bladder cancer in the context of air and when education is very interesting to us and that would likely be one of the expansion cohorts that that we would pursue.
And we're still you're deciding on what the the various other.
Expansion cohorts would be for Oetwo nine and we'll we'll provide more information on that once we establish the recommended phase two dose.
Got it thank you very much.
Thank you. My next question comes from Doug can with BMO capital markets. Your line is now open.
Hi, Thanks for taking my question first on 610, <unk> Oh I wanted to go back to the enrollment criteria for the first line patients Oh, you changed that.
Towards the beginning in <unk>, a loud patient 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 like Horn arm, maybe they had less severe disease and whether you think that can have an impact on the outcome.
Yeah, I think I mean look I think we did.
I used the enrollment criteria from our original.
Criteria for arm three it was originally designed to enroll anemic patients only.
After we started to see some of the of the effects. You know there was a lot of enthusiasm from investigators to treat patients who were not I mean.
You make a baseline.
So we did we did go ahead and and open that up to kind of the traditional kind of essentially what part of the labeled population for.
For JAK inhibitor therapy.
So we.
You know I'm not sure that there should be any any.
Major differences that you should be thinking about relative to baseline characteristics I mean, we're not.
I don't think we arent, where physicians are trying to hand picked 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 there's likely something that's driving that at that makes them to be less less well and perhaps more sick.
But overall as you kind of scan down the various inclusion criteria nothing nothing is popped out to us.
As being.
Correlative with with response, we've seen kind of responsiveness across.
A range of different about parameters.
You know things that you look out for me and characteristics and well continue assessed that with more data and more patients I think they'll become increasingly clear.
To everybody.
Great, Thanks trigger and for Htwo five.
When you make that go no go decision.
What would have clear signal looks like what's the hurdle and and TTP and Oh.
Are there other biomarkers are measures that will factor into your decision.
Yeah, and it seemed that I just need.
I'll start to hit the prostate cancer is really dynamically evolving.
Area you know we've got.
You know the Aer our agents kind of are all.
Duking it out to move upstream.
And you know some of them you know.
Kind of a 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.
Looking at kind of historical data.
As benchmarks as well as our own control arms that we built into the study as well as kind of evolving data from competitors to make that decision. So it's not it's not a it's a multi factorial type a decision for us.
Just as we went into this we are we were looking for a clear.
Operation for instance in the trouble five for then it'll be the might arm would be randomize. It ends with them I think the first order would be that we want to see a clear separation.
Significant from Enzalutamide.
But then also reflecting on historical data that was subsequently published after we started the study shows.
Clinical time to.
It is on the order of two to three months.
In these patients and so I'm showing a significant improvement over that.
Would be something that we're shooting for and then I think we also want to you know assess and some of the latest data that have been published around.
Somebody's other classes of therapy that I've mentioned to assess.
I'm going to what the path forward could be for each two inhibitor in prostate cancer.
Okay great.
And if you don't continue development well, we'll file I would it be reasonable thinks that you will.
HM two nine in prostate cancer first since you have all this experience.
Yeah.
It's possible I think the trial that we set up here is extremely rich with data I mean, we'll have <unk>.
You know 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 if we if we had hypothetically a signal that was intriguing, but not you know very clear in terms of the total of five.
Standpoint, we could we could take.
All those learnings and apply those dojo nine as a hypothetical.
And so we haven't yet decide to do anything like that but we havent rule that out.
Okay. Thanks, Thanks for taking my question.
Thank you don't think.
Thank you Sir our next question comes from my calls with Baird.
Your line is now open.
Hey, guys. Thanks for taking the question and congrats on all the progress as well maybe just another another six kind of question for you and the manifest studying and particularly in frontline patients here.
Maybe you can just just talk about the current status of enrollment you know versus your target of 100.
<unk> patients and just just maybe how that's tracking versus your expectations.
I'm just curious if there's there was any uptick post the ash data.
Yeah, well I think generally there was a lot of excitement and enthusiasm post ash and even even pre ash there was.
From the investigators who were aware of the data there was a lot of excitement, but as you made it public has been.
Certainly I think lot a lot more enthusiasm more broadly.
Yes, I think I think maybe all I can say really on enrollment is that we're really pleased.
And.
It's a meeting your expectations.
Got it and then maybe just.
A quick follow up on on T. Rowe nine so.
Maybe you can talk about some other potential expansion cohorts you know you mentioned maybe bladder.
Actually prostate.
Maybe just maybe some others that you might be considering or how many are considering.
Right.
Yeah, there there.
Our several several opportunities we think to kind of move into.
Both indications that are well known appreciates too as well as things that have not yet been considered among the various easy to inhibitors or in the clinic and we haven't finalized our decisions on which which.
Expansion cohorts were going to pursue and so what will largely be driven by kind of strategic considerations around.
Things like utilizing infrastructure that we built in various context and and also to really test the potential of a best in class each two inhibitor, which we hope you Cpis your two zero.
It is and make some you know bold bets that really expand the opportunity, but beyond that we're not quite ready to disclose any more details about whats cohorts.
Got it thanks again.
Thank you and next question comes from Mark from with Cowen. Your line is now open.
Thanks for taking my question.
First just with the update that you're planning to give that you change your interest in well get the 24 week on it gets pieces, we've already seen in the people that were already in the baseline characteristics and.
Yes, but you've already been enrolling more patients that presumably some of them will.
Yes, the time points you present on before like week 12 in places like that.
Should we expect to see any of that either DHS as well just the earlier time points.
Earlier than the 24 week data.
Yep.
Yeah, I think I know, we've shared that in the past and it's reasonable to assume that that could be a.
Ability, we havent, yet decided exactly what data will be presented at had he oh, we do know that 25 30 patients you know will have crossed the 24 week threshold. We think that's a really important time point based on.
It's important for regulatory perspective.
And certainly I think.
You know if there is important.
Data out there that would would put kind of inform how how the drug is behaving you know we feel that they will be important to get that out there. So we'll what kind of assessed to see what's what's meaningful what's different and and ER and share and share everything with you that we think falls into that category.
Okay, and then maybe just following on the prior questions about enrollment and given your in 2019, you're able to.
Show that.
It's combination was can be done safely in terms of.
Platelet counts and maybe even has benefits on Mimi as well yeah has that changed enthusiasm kind of with in.
The populations as the whose enrolling at all.
I would think that would lead to more people with baseline anemia, and more people with baseline yellow platelet counts wanting to be on the trial, but [laughter] have you seen that.
Yeah, I mean, the again there hasn't been any bias towards the selection of patients you know.
With you any particular.
Baseline characteristic.
So I think we set certain minimum enrollment criteria for for platelets for example.
And as long as patients qualify there they are welcome to enroll and wouldn't stop that and so.
There hasn't been as I don't I wouldn't mystery point any specific kind of trend one way or the other with regard to that.
Okay, Great and then one last one just again each two franchise fear you touched on this is maybe go I guess, if you had a intermediate result from Prostar that maybe you would still.
We'll pursue it with 12 your follow up with 12 of five.
Hi, sorry, with ocular nine given the proposed benefits, but also if you even if you see a clear signal is at that point you have.
<unk> recommended phase two does that look seeks and everything with two nine given the proposed benefits would you still going forward with one of the five in that.
Adding or would you then also look to pivot to do use it to nine given the yeah. The proposed benefits as a molecule.
I think we'll just have to wait and see what the data how they're going to shake out I mean, if we're ready to move into a phase three that's still substantially further along than O'toole nine and so I think it just depends on how exciting the results are.
To me Thats.
Termination.
Okay alright, thank you.
Thank you as a reminder to ask a question you want me to press Star one on your telephone.
Our next question comes from Sylvan Tech and with Oppenheimer. Your line is now open.
Hi, Thanks for taking my question on them and congrats on.
The quarter.
Just a quick number I've a follow up.
And at the front line.
Cohort did you teacher out additional sites or central Florida enrolling patients enrolled we see data from these additional.
Sorry can you repeat your question Sylvan.
Well, you're did you want to expand the frontline myelofibrosis cohort did you add additional sites or did you just to expand that number in existing sites and if there are new sites, where we see did you have from these additional sites.
Oh, presumably you will see data from sites that haven't maybe we've.
It's the I had a site kind of activation is more of a rolling kind of thing I mean, we been activating new sites from the beginning the study and you know have I've gotten any sites and we'll continue to kind of activate new sites and so that would lessen necessary linked to the expansion, but more just kind of how we are aiming to kind of progress with.
With with the development of this molecule in the current study as well as the next study.
We do.
So so with that you know with kind of more sites coming onboard they'll definitely be an increasing proportion of patients that are coming from more and more sites.
You know the early patients were not all coming for instance, so from one side they already.
The only represented a pretty diverse diverse array of sites that were already active.
Okay, Great and then I think I'm I'm still probably a little bit confused about could you share with us the ER discussion how they exactly work with the regulators are what somewhere between U.S. and you or whatever.
Almost <unk> differences.
And kind of what is your baseline expectations in terms of the outcome for frontline is it that they would just a proof the trial as your presenter today I'm on slide five I believe politics.
Or and what is kind of like your baseline case for the second line indication.
Where you're thinking accelerated approval or not or another phase three for second line.
Thanks.
Okay, Yes, so maybe I'll start with a question that you asked about kind of differences between kind of U.S.
In Europe, I mean, I think it's.
Maybe the first thing I'll say that the phase three that weve.
And is meant to address the.
Requirements for approval globally, and we'll certainly want to.
You know confirmed that assumption as we meet with regulators outside the U.S., but.
But we believe that that should be the case.
<unk>.
So I think stepping back from that you know I think generally kind of end or kind of drug development. As you know you know in Europe, there tends to be a oh, let's have all likelihood to achieve kind of a new approvals based on surrogate endpoints.
Into the randomized studies.
Are much more meaningful.
So I mean, you asked me what we expect we expect that that continuing to be the case in this context as well.
Having said that there seems to be a bit more harmonization legally between and U. S and X U.S. regulatory authorities and we will seek to kind of.
Have those are understanding of discussions around that as well.
So, but what kind of again just to kind of some up randomize phase three is meant to be the basis for full approval and if there are accelerated strategies to pursue will bring those discussions up and see if they if they hold that we think that there's.
You know these potential to discuss those possibility based on all three of our arms.
And again as I mentioned earlier, there's there's just a lot more information that we have currently about whether that we think that's likely or not that's what we're just putting ourselves in a position to have those discussions.
Great. Thanks, Thanks for taking my question.
Youre welcome Sullivan.
Thank you I'm not showing any further questions at this time I would now like to turn the call back over to do you ever thought for any closing remarks.
Okay I just wanted to say thank everybody for joining our call. We really appreciate all of the the.
Just 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 and indeed Nate.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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