Q2 2020 Constellation Pharmaceuticals Inc Earnings Call
Thank you for standing behind and welcome to be constellations Pharmaceuticals second quarter 2020, <unk> earnings Conference call.
At this time, all participants are and I listen only mode.
After the speakers presentation, there will be a question and answer session. Please be advised that today's conference is being recorded.
To ask a question during the session you will need to press star one on your telephone if you require further assistance press Star zero.
I'd now like the hand, the conference over to your Speaker today. This is Keith kind of poor. Thank you. Please go ahead.
Thank you Bobby.
Morning, everyone and welcome to this conference call to that consolation second quarter, 2020 financial myself and operational performance.
Eating I don't call. This morning, I kick or White house constellation Chief Executive Officer, Dr., Jeff I'm, sorry, our new Chief Medical Officer, Dr., Patrick Troyer, our Chief Scientific Officer, I Am I believe I Chief Financial Officer.
Please turn to slide kids.
Before we begin I want to point out that our presentation. Today will include forward looking statement, which are subject to certain risks and uncertainties.
Actual results may differ materially due to various important factors, including those described in the way after section as well that's discussions with potential with uncertainty and other important factors.
In the company most recent filings with the Securities and Exchange Commission, including the company quarterly report on form.
Q4, the quarter ended June Thirtyth, 2020, and now I'll turn the call over teacher.
Yeah, and good morning, everyone.
I'm very pleased to have three members of our management team joining the call Jeff country or new CMO is the medical oncologist with over 20 years of experience in drug development.
Prior to joining constellation he was chief development Officer, I keep hearing company, where he oversaw the development of the company's global portfolio.
Nickel therapeutics for Western markets. He began his industry clinical research at Bristol Myers Squibb, and subsequently circumvention positions early and late drug development and medical affairs at Pfizer.
In Bristol Myers Squibb.
Our Chief Scientific Officer, Patrick trader. Many of you know is getting your call today.
Patrick is one of the founding scientist and he is internationally recognized for his expertise and crummy, congratulations transcription and oncology drug discovery.
You beat your discovery translational science and CMC organizations.
Of course, you all know him a read our CFO. He was instrumental in building constellation financial strength to enable us to develop and eventually commercialized.
Programs.
Please turn to slide three.
I constellation, we're building a fully integrated them some companies in order to bring important medicines to patients with significant unmet needs.
Underpinning of ambition is your investment any productive discovery platform, which in turn driving sustainable pipeline of innovative Clark.
Develop and commercialize [noise].
Specifically, we believe that we can transform standard of care as well if I break this with your debt inhibitor cpis jurisdiction, which has the potential to be disease modifying.
We're working to deliver what we believe it's your best in class each two inhibitor Cpis your cheesier nine which had the profile that can expand the addressable patient population this promising faster.
And we also aim to discover and develop novel and impactful hematology oncology treatments from or discovery platform.
To accomplish our vision.
Constellation as a fully integrated commercial stage company, we're assembling experienced leadership team across the company could garner like of the drivers.
Including the three numbers that we have here with us today.
Please turn to slide four.
I'd like to remind you of the next steps for lead programs.
We Cpis your 610, we plan to start phase three clinical trial.
We intend to also provide an update on the program. Later this year that include additional clinical data and new translational data further support the disease modifying potential of Cpis years 610.
With Cpis your to do your nine were in the dose escalation portion of the sees when she study and we anticipate determining the recommended phase two dose in the second half a year and then moving into the expansion cohorts.
Well talk more about the phase two development, when we announced the recommended phase two dose.
Well look at these product candidates emerged from our own discovery platform and we intend to discuss additional programs that emerged from reference I don't Liberty.
Before describing our program specific developments I'd like to give you an update and how close like 19 isn't packing operations and Howard energy dependent Nick.
Prior to coated the pace of enrollment manifest what's ahead of schedule.
The trajectory slowed near the end of the first quarter. It started to pick up in second quarter, and we continue to target initiating benefits to our phase three clinical trial for Cpis. Your 610 in the second half of 2020.
The phase one trial for Cpis, New York City or nine is proceeding as planned.
Our clinical supplies material Oliver clinical studies is on track.
Lastly in May we began reopening our offices in accordance with the directors juices and their facilities are now open with a focus on our laboratory personnel.
Please turn to slide five.
I'd like to discuss the progress that we're making cpis your 610.
To recap during the second quarter, we presented results from April 17th data cut of manifest after your teeth European Hematology Association meeting.
Those results demonstrated that cpis through six Ken in combination with Ruxolitinib worth monotherapy showed preliminary evidence of clinical activity you potentially potential disease modifying that.
In on three in JAK inhibitor nave patients, 60% of patients treated with Cpis years 610 in combination with Ruxolitinib achieved actually eurthirty five at 24 weeks.
Historical phase three studies Ruxolitinib alone if you're at 35 rates were in the range of 29% to 42%.
In addition, we've been enrolling in various cohorts JAK inhibitor experienced patients.
In this difficult to treat second line setting we saw a piece of 21% transfusion dependent patients Cpis you were six said monotherapy and 34% of transfusion dependent patients as an add onto gets lifted convert transfusion independence.
24% of non transfusion dependent second line patients in monotherapy and 22% as an add on to Rex achieved Netseer 35 in.
In a similar setting and simplify to JAK inhibitors are shown to have if your response rate of 6% to 7%.
Cpis used 610 was generally well tolerated as a monotherapy and inc. any any combination ruxolitinib in both first and second line.
We also generated a preliminary data showing hemoglobin increases and boehner hybris is improvement with Cpis Your 610.
Please refer to where he helped posters posted on our website and recent filings with the FCC for additional information regarding the activity in safety of Cpis years acted.
We believe a cpis. There's 610 has the potential could be to these my point therapy and redefine the standard of care and now we're pleased with the next day didn't seem to date and we're excited to move forward.
Please turn to slide six.
Now I'd like to talk about the path forward with Cpis Your six Ken basin, the discussions you've had with yet.
There are two key messages I'd like to convey regarding these discussions.
I'm pleased to share that we've aligned with the FDA on the design of our global randomized double blind pivotal phase three trial in JAK inhibitor naive patients called manifests too.
We're on track to initiate the study in the second half a point each way in a moment, Jeff will share with you the details of the design this trial.
Second we will continue to build on the collaborative dialogue that we've had with the FDA and we'll explore other opportunities to bring cpis your six into patients.
And now Jeff will take us the design of benefits too.
Good morning, I'm Schuff Humphrey, the Chief Medical officer, constellation and I'm excited to have joined the company.
I believe in constellations pipeline I'm excited about Oh, 610, and I look forward to helping to bring Cpis zero six tend to enough patients in need as soon as possible.
Trigger mentioned, we've had a collaborative dialogue with the FDA and we look forward to continuing that collaboration.
We are in the final stages of preparation to initiate mannafest two and are eager to enroll the first patient in the second half of 2020.
The trial is designed as a blinded randomized pivotal study, but cpis euro 610 in combination with Ruxolitinib.
Versus placebo plus ruxolitinib in JAK inhibitor naive patients with primary myelofibrosis or post P.T. or post P. myelofibrosis, who have advanced disease with splenomegaly and symptoms requiring therapy.
Mannafest two is designed to enroll approximately 310 patients we plan to randomize patients one to one to the Cpis Euro 610, plus ruxolitinib arm or the placebo plus ruxolitinib arm and to stratify patients based on the dips risk category, the platelet count and the spleen volume.
The dosing schedule is based on a 21 day cycle.
Yeah Zero 610, and Ruxolitinib would be does similar to our current dosing regimen and manifest.
Since would start at 125 milligrams of Cpis Euro 610, once daily Ruxolitinib would be does that five milligrams below the label dose in the first cycle and would be app to label dose starting at cycle too.
The primary endpoint to this study is Fcr 35 response at 24 weeks.
A key secondary endpoints of this study is 50% improvement in total symptom score for T.S.S. 50 at 24 weeks.
Other endpoints that we will measure include bone marrow fibrosis grade improvements.
Duration of transfusion independence.
Rate of RBC transfusion for the first 24 weeks and hemoglobin response.
The trial is powered at approximately 90% and we expect that will take a couple of years to complete.
Please turn to slide seven.
We believe there are opportunities to expand the use of Cpis here 610, it more broadly into indications and other hematologic malignancies.
As one example, today, we are announcing that we plan to initiate a new cohort palm for in manifest.
Studies Cpis, there were 610 monotherapy and essential thrombocythemia or E T. In the second half a 2020.
He is a myeloproliferative disorders that can progress to enough and to ml and it's characterized by excessive production of platelets as well as symptoms that means fatigue like lightheadedness headaches vision changes and an increased risk of blood clots.
Please turn to slide eight.
We are exploring Cpis 610 in E T. Because we know there was a strong mechanistic rationale for such treatment.
We know that Cpis Euro 610 can reduce platelet counts and in manifest we'd see normalization of platelet numbers since some patience with very high platelet levels at baseline.
We also know that E T patients can be symptomatic and we've seen a profound impact on symptoms from Cpis 610 in manifest.
As you can see in this example, a post P.T. enough patient with high baseline platelet counts in the manifest study achieved normalized platelets and meaningful improvement in total symptom score.
Data like these are the the basis for our rationale for exploring E. T. Further in arm for.
In arm for which we plan to begin in the second half and 2020, we will explore proof of concept of Cpis Euro 610 monotherapy.
In treatment of approximately 20 hydroxy urea resistant or intolerant patients with the tea.
The primary endpoint to this study will be complete hematologic response within 24 weeks as measured by normalization of platelet count and white blood cell count.
It's a key secondary endpoint of T.S., that's 50 at 24 weeks.
This cohort will help us not only to understand Cpis. Your 610 in this population, but also to identify endpoints that can be useful in a larger pivotal trial.
And now I'll hand, the call over to my colleague Patrick.
To discuss C.P.I. zero 209, and our discovery platform.
Truck.
Thank you too.
I'm, Patrick Troy I could see its own constellation and I'm excited to share with you detailed although second program in the clinic, the easiest to inhibit the Cpis euro two zero or not.
Please turn to slide nine.
You will recall that it's too if they'd be done that's lutron right.
Its role is trying to isolate he 73 at like 27, and thereby sunset place expression of specially sets of gene.
We believe that.
209 has the potential to be a best in class easy it's doing we'd be though.
We decide.
209 to improve on first generation you'd be doing he because in the number.
Including increased potency longer residence time, and maintaining exposure levels by not reducing its own metabolism.
With that type of profile, we came out with sued the very broad application of easy it's doing he'd be soon.
Doubling down on context sweating, the assets to inhibit that already have shown clinically <unk> and when you reach to weaken oncogenic driver.
You know jogs is with all the oncogenic driver possibly.
Oh, absolutely flooring additional context with euro 209 maintain the feel with Rothmans Houston.
<unk> told them you need be Andy ROI in Pittsburgh lethal relationships.
And we are planning to explore he'd be idea to dealer nine in all of these contracts.
Please turn to slide 10.
This slide presented data that corroborates the three key properties. So.
You are 209 that support its best in class potentially increase potency longer residence time, and lack of induce me probably.
The table on the left illustrates the superior biochemical potency of Cpis, you want to see over nine compared to other clinical stage easier to do indeed.
They don't the middle showed the remarkably slow walk freed up.
Cool nine compared to another huge doing.
Indeed, 18 at resident Simulmedia to do that potentially differentiating.
On the right you can see exposure profile Cpis 209, when orally administered to my office seem to be though the one and maintenance of Cpis 009 exposure at steady state up to 12 basis once daily dosing de 12.
This is consistent with the observation that the compound that navient use its own metabolism.
With this profile.
Dealer to dealer nine makes frac, the well therapeutic potential of each to biology.
Please turn to slide 11.
The problem just highlighted.
Our translating into superior if he could see in pre clinically mouse model on a once daily dosing schedule with respect to dose use and magnitude of UBS tumor growth inhibition.
Here, we see data from two in vivo studies showing seed.
Oh nines performance achieving tumor regression in models, both seemed like the logic campus and probably too.
It's comprehensive easier to target engagement it cheap flight potency long resident climb and a favorable exposure profile may allow us to harness deep or responses.
And to expand into patient population, such as patients with sit in Saudi too much.
No not adequately with first generation easy edge to inhibitors.
We are currently at 15 Cpis dealer to dealer a nine in phase one dose escalation study in an all commerce solid tumor patient population.
We intend to establish safety parameters and recommended phase two dose in the second half of the year and to begin now phase two expansion cohorts shortly thereafter.
We plan to explore multiple disease conflicts with Cpis, you're a 209 based on biomarker driven strategies, including the assessment of mutations in jeans like each to every Connie.
Well they lose the date on the development plan around.
It was zero nine as we determined the recommended phase two dose.
Please turn to slide 12.
All the assets we have discussed today have emerged from our internal discovery efforts and thus I would like to take that made it to these cuts constellations oncology research platform, which continues to be an engine up all current and future drug discovery pipeline.
As we continue to mature as an organization with an increasing mechanically development activities. We have established a translational focus too I think <unk> proprietary biomarkers and features a product candidate that differentiate us from competitors.
The identification of myelofibrosis at the lead indication for CTP 610 clinical development is an example of how it's front bleach, let me focus researcher.
Sick.
Without increasing investment in development without leveraging our increased he sees every expertise and directing discovery folks around certain types of cancers.
Such as myeloproliferative neoplasms, well, Jamie urinary campus.
To strengthen our inc. a product candidates.
You are a 610 and eat the idea to zero nine we've built around those product candidate and I'll. Let me speaking that didn't keep buying mechanisms that combined with those product candidate or can it saying Oh, great NBC Ccs with additional innovative product.
And third we continued to take advantage of a strong and proven expertise and track record in chromebook in regulation and gene control to identifying novel mechanism, but may create compelling future product opportunities.
And I'll turn it over the floor swim.
Hey, Mike.
Thanks, Patrick and good morning, everybody. Please turn to slide said team.
First I'd like to discuss our progress toward meeting a milestone for twentytwenty.
As planned we presented encouraging honestly stayed pretty hard in June.
We continue to expect to initiate a mannafest two clinical trial in the second houses Twentytwenty as discussed earlier.
Importantly, we also plan to provide a further update from the sale to manifest study later this year, including both updated clinical and new translational data.
Translational data could help to to elucidate with potential disease modifying properties of CP iOS extent.
We're in the process of submitting abstract Ashley we related to this program.
Please note that those abstracts are based on the same April 17 States <unk> included in our Ito presentation and does contain updated clinical data.
So again, we expect to present updated clinical data at Ash meeting itself assuming were accepted.
Rather than in the upside.
Let's see I have to a nine we continue to anticipate providing an update in the second calls at the year, primarily focused around establishing a recommended phase two dose.
Now, let's turn to slide 14 to review the financial results for the quarter.
We had a net loss attributable to common stock holders of $29.8 million in the second quarter, which was in line with our expectation.
The net loss per share was 70 cents in the second quarter compared with 80 cents per share in the second quarter of 29 team.
R&D expenses increased by $6.7 million year over year, mainly due to work related to Cpis 610.
Personnel costs also increased compared with the prior year quarter as we continued to build out our organization.
With our recent financing cash cash equivalents and marketable securities were $520.5 million as of June 30th.
Which we expect will fund our operations into mid 2023.
We plan to use these resources to complete the manifest trial to complete Mannafest two phase three clinical trials with Cpis 610 and to start to build the commercial organization needed to launch the compound.
In addition, our cash will help us to complete the phase one two clinical trials, the CIO, two or nine as well as to support have discovery platform.
That concludes our prepared remarks. So this morning, so I'll turn things back over to the operator.
Well they would you. Please open the line for question.
Thank you if you would like to ask a question simply press Star then the number one on your telephone keypad well pause for just a moment to compound mcewen a roster.
And your first question comes from the line of AMCU, Pam Rama with JP Morgan.
Hey, guys. Thanks, so much for taking the question.
Two quick ones from me how are you thinking about the second line opportunity go forward strategy and the M. Aspen did regulators either you or any feedback on this treatment setting and any differences to highlight between their transfusion dependent or not dependent population.
From regulators and then on CP I O to O nine.
The sequential biomarkers, you'll be looking out for a potential enrichment strategy. Thanks, so much.
So thanks for the time for the question and I'll start with that and then maybe ask.
Jeff or Patrick to add additional remarks if needed.
So so I think the first question you asked was on.
And the path forward in in second line and.
You said in the past our focus really has been in naive patients to be able to drive to a a broad label.
Based on a and approval.
Pathway in that first line setting in the late setting, but we did obviously have generated substantial information.
From our various cohorts of patients in the second line context, including exploring novel endpoints like transfusion dependent its conversion and we had reviewed some of those data and pathways with the agency and we're incorporating the constructive feedback that we received and we'll continue to access additional potential paths.
Forward.
You have specifically on transfusion dependent is conversion.
We determined is that that is certainly an endpoint that basin or discussion with the agency that there's this belief that that they are an endpoint, but that speaks to unmet need you. At this point, we don't have additional information on how to how to drive specifically in coordinate patient population, but we'll we'll incorporate.
The feedback that we got and.
Potentially have additional discussions and we.
We have put something you could say there will certainly report back on that.
Yep and that she and I know Tonight.
So I just wanted to go ahead of it because additionally, when it yeah, sorry about that yeah. No I just wanted to also point out that you know we have aligned with the FDA now on the key elements of the Mannafest two protocol and we are very excited to start the first patient in this year.
And then trigger I'm, sorry, probably still your Thunder you are about to say on Cpis. Your 209, the biomarkers of interest as Patrick said are easy H. too and arid when it goes will be the biomarker strategy for.
Extension of the tier twos here and I.
Thanks, Yeah as well as other potential avenues me Patrick you want to do want to chime in on that.
Yeah. So what we publicly disclosed is clearly an interest around every bonnie.
I think it's clear that easiest who is part of it but they all the molecular biomarkers that come from our preclinical as well as our clinical data that may inform future development of Cpis zero 209.
Got it thanks, so much for taking my question.
Your next question comes from the line of Brian Abrams with RBC capital markets.
Hey, guys. Thanks, so much for taking my questions and congrats on a and all the progress.
A couple from me on the New Mannafest two study and then one on manifest one.
I guess on Mannafest two.
Could you confirm that a single study would be.
Sufficient for approval and if there are certain a P value a threshold that you would need to meet manifest too.
Yeah, I think so the question I mean, certainly a trial needs to meet statistical significance and we're very pleased that weve power to trial at 90% for the key endpoint of SCR 35.
And the F.D.A. has aligned on the design it manifests too.
You know there and I think yeah. Those are those are things that we're excited about the F T will never.
I'd make a decision about the adequacy of your development program.
Until you have data right depends on the data. It's always heard he was sure Brian I think I think it's fair to say that recently discussion that we have we feel pretty comfortable that.
You know one study is sufficient.
Got it Okay. That's helpful. Then yeah with respect to the the powering assumptions can you maybe talk a little bit more about.
Specific delta on SP Arent TSS that you guys are are powered at 90%.
For and then I know it was mentioning we're filing this morning that there's the opportunity to re size the study on to adjust the.
To.
So I guess it just a sample size as you go along or are there specific.
Points, where there will be interim analyses to support potential reciting are there interim futility or.
Efficacy, that's an hour analyses built and at that those points and would you be plenty to announce those.
Yeah. Thanks for the question I mean as I as Chiger said, the SVR 35, we have as an estimate from manifest to 63% compared to historical rate of 29% to 42% from the pivotal studies of Ruxolitinib, we haven't mechanism for re sizing the.
Trial and at this point, we're not ready to discuss details with that mechanism, but we feel very comfortable that we will be 90% powered on t. endpoints that are important for approval SCR 35, and TSS 50.
I can put shot of study.
Got it that's really helpful. Then and then one last one I, maybe just building on that your answer to the prior question. Just wondering if you talk a little bit more about it sounds like the current manifest data is not necessarily sufficient to support.
Early approval of the combination of 610, plus Ruxolitinib did can you can you talk a little bit more about any.
Additional clarity you may have gotten from the FDA, what they might look for us to potentially support them more rapid path, which would be looking gearing more towards monotherapy updated data continue more patients a certain threshold on on a particular endpoint that you could potentially aim to head I know the frontline is.
Sort of the primary goal, but just wondering if there's any yet a if you could expand on some of these other things you might be exploring thanks.
Yes, yes, I'll start with that Brian and then and then Jackie should certainly trending with additional information you I think.
You said in the past, we believe that Ah you know in particular for the naive patient population that a randomized study is is probably necessary to tease out the contributions of the of the components you having said that we think that there's a sufficient excitement based on the data do you happen benefits to to really sick.
With me I'm, sorry manifest both both in the <unk>.
But also from some of the experienced patients, including monotherapy that it really supports the notion that we have.
You genuine activity being contributed here from from Cpis, Your six and it's very very meaningful.
We can't get into specifics on.
Additional possibilities around.
Potential pads alternative plans beyond that today.
Say that we had very constructive dialogue, we've gotten feedback that will help us to determine.
Additional has and will incorporate that feedback and like we have additional discussions overtime.
Makes sense. Thanks, so much.
And your next [laughter].
Sorry, if I wanted to make sure that checking like anything more to add to that no well I would just fat that you know we have fast track designation. The FDA has been very open to having repeated discussions with us had they and we are collaborating to look for the earliest pass and but it is clear that.
We and each understand contribution of components has chiger said.
That both SCR and TSS 50.
I'd need to be.
Met in the Mannafest two study thanks.
Thank you and your next question comes from the line of Marc Frahm with Cowen and company.
Hey, it's thanks for taking my questions.
Maybe just following up on the left for questions about the FDA discussions.
Together some of your comments.
Seems like you're given the the necessity to determine the contribution of each component of a combination.
The only potential way forward and second line as a monotherapy then using kind of the manifest one data. We you know given your reluctance to started phase two trial, a phase three trial the to randomize given that the timelines, but heavily over I personally.
Sorry, Mark can you can you repeat the question I want to make sure I just I just got it quickly just.
It seems like you're really stressing the having to figure out the relative contribution of each component of a combination, which obviously report which kind of requires a company area.
Randomized trial.
So it's in terms of your discussions with the FDA on the second line opportunity.
Does that mean that the only path forward that you guys see kind to continue pursuing with the FDA is as a monotherapy or are you still discussing the combination data as well.
Yeah, I think that we see potential opportunities across the board.
And and I think it's a little bit premature for us to comment specifically on on what those could be in the second likewise, we have a little more work to do to incorporate some of the that he definitely gotten.
But that will will definitely be able to respond to that overtime.
But but we're very excited about the data that we have in the second line, both as a monotherapy, but as well as an add on to reflected as you know that there's plenty of strategy that there that folks are pursuing.
In that setting with creativity as well.
Okay, and then also commentary about the FDA clearly, believing that conversion from transfusion independence to transfusion independence.
It's an unmet need but you're still exploring ways forward as the debate with the asking me on how to default and transfusion dependent in transfusion independence or is it more about kind of the effect size that you're showing and how many patients and those types of aspects of the did.
Yes, I think a I don't think there's a big necessarily on the on the the.
Unmet need as I mentioned I think its injuries you bring much recognize as this is that when they should become transfusion dependent but they are significantly hampered both quality like perspective, but also from a perspective of being anemic is.
Creates a.
Ignostic factors one of the most important ones. So from a I think that your point for me a trial.
Design perspective, as well as endpoint lesson in perspective, just getting clarity.
And how did decline transfusion dependent.
And developing the evidence that's necessary to support the you how that translates into clinical benefit or things that will will focus more on as we as we examine examine what potential.
Okay. Thanks, that's helpful.
Quickly on virtually zero nine.
I recognize it's.
[noise] abroad phase one that you know very open enrollment criteria, but given the patients that youve actually seen enrolling the trial.
It's are you do you think there's chance that with this initial data set we could start to see the differentiation clinically versus the exists easy to inhibitors that are you guys are put in crank and others have yeah.
So pursued or is it your screen to be you're too broad of a population too early yet is there I mean, what I'm sure. We'll certainly try our best but but this has this was defined designed as a all comers solid tumor.
Dose escalation cohort, which.
You know can be quite diverse it it's it's patient population.
Okay. Thanks.
Your next question comes from the line of Mike.
Ill with Baird.
Hey, guys. Thanks for taking the question.
Just had one on the phase three Mannafest two study.
So you guys are on track to start the study in the second half, but just wondering can talk about what are the remaining steps to getting that study underway and then are there any things you're doing to sort of manage some of the potential challenges created by the ongoing pandemic. Thanks.
Hey, Mike, Yes, so nothing has actions on our guidance like manifest you as we continue to remain on track and as we've indicated before it's the pieces that are in our control can have the operational elements.
Around you know site recruiting and contracting you, that's well on well in hand and underway.
And the the piece that we we've been keeping a careful eye on his and starting very closely as we as we identify site is their ability to to really manage these patients who who will will need to be cared for through this uncertain time with the coated.
And so that's really kind of the piece that we are just making sure that we've examined and getting haven't hand, you very closely with those but particularly those are the site.
In case in terms of specific plans in terms of how to manage.
It's very much in line with ER with how we're managing today, which is to.
You ensure that there is flexibility on how patients can receive their drug.
In terms of you know ship directly to them, a as well as flexibility around if needed timing in place, where we're data can be collected whether its labs or or.
For imaging data.
And so we could be we put a built in those measures to be able to to ensure a good integrity. In this study, but very similar to what we're doing today.
Okay, great. Thank you.
Your next question comes from the line of bringing Ayman from Jefferies.
Hey, guys. Thanks for taking my questions, maybe just to start on manifest too I think the trial is gonna be enrolling about 35% more patients. So then what abbvie announcement clinical trial the stock of when the vet o'clock could transform one trial. So just trying to understand I think your comment.
It's on resigned saying whether.
You would look at analysis had a lower number of patients and manifesto.
And I guess second question is what's the treatment effect that you're assuming on the primary endpoint over the control arm.
Yes, I'll start with the competitive piece and then on media as Jackie comment specifically on the on the statistics.
You know we think that.
First I think it's hard for us to really comic con and what Abbvies designing certainly took notice of of their other trial design.
Do you wanted to highlight that you from what we've seen publicly from then you need to data in a limited number of patients in second line and so we haven't really seen much needed to make any judgments. If there's any their report on in the first line setting.
You contrast, we've had.
You know as ever lasted update you had 50 patients a day in the first line setting, which which has given us a lot of comfort around how we are thinking about the statistics of he said your 610 minutes to.
And with regard to the interim analysis I think we've got a lot of comfort around the separation that we're seeing around SCR, Yes, Jeff mentioned before.
Response rates north of 60% versus well in line with 30% to 40%, but could you expected rocks and so there's there's ample room to be a sufficiently powered even with the most conservative assumptions.
You can make around what rux can do based on historical study.
And really what we are thinking through with the re estimation piece of it is TSS isn't a a single arm study as you can only only in traffic so much from those those endpoint those data and so.
As you get some more experience will be able to make sure that we.
Adequately powered the study for parties as well.
Yeah, I don't have much sad, but Brian we can't really comment on Abbvies design as Chiger was saying we generated a very large dataset in the relevant population we've sized to study we've gotten alignment with TFT on the key elements and we heard a lot of enthusiasm from our phase two investor.
Gators so we're focused on the base case on phase three.
Manifest too as our approach the market.
And then maybe just a question on the E T trial within manifest the arm for component.
What those are you planning to evaluate.
Also are you looking at improvements in ERP related symptoms like fatigue, ditching bone paying a night swipes.
Yes. Thank you as previously mentioned by Emma We will guide on the recommended dose phase two dose later this year.
And we will be measuring.
Their symptoms, including fatigue, and as mentioned the MPN symptom assessment form. So those are those corella to send some changes will be measured as well.
And as I mentioned, the primary endpoint, maybe I can just jump.
Sorry, if I could just something in that yes, I think the dose that we would look at for each he.
Would be the but likely be around the MPD, but we I would extend which is 25 when today.
And so that's probably the dose that we would use and then pizza.
Great. Thank you.
Yeah.
Your next question comes from the line of Crap.
Steve.
These are a condo, but to it security.
Hi, Thank you so much for taking my question and congrats on the progress has the fee because he alignment with the F.D.A. that you mentioned, where there any changes to the PC design the agencies recommended.
No I know just came up earlier as well, but just wanted to clarify where you were with drug availability will you have everything ready by the time. The trial starts I know you mentioned earlier that you have multiple vendors now.
So will you are you thinking more in terms of having a steady state supply as you go through the phase three study.
Thank you.
Yes, sure so you're on the the design and specific kind of components of it no. There's nothing I think that there would be is surprising or any any feedback that was out of out of what we expect it to receive their new is a very constructive dialogue and.
As Jeff mentioned.
The design will be very similar to what we've been doing already with benefits to I'll start with manifest one argument that's too.
In terms of drug supply.
He we've had ample experience now in terms of manufacturing jaegers extending continue to.
Make a drug supply on a continuous basis that that is.
Lets sufficient inventory to continue to drive forward.
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Great. Thank you.
Your next question comes from a line of Jay Olson with often Oppenheimer.
Oh, Hey, congrats on the progress and thank you for taking the question.
Can you comment on any communications, you had with X U.S. regulators regarding zero 610, and as you plan to build out your commercial capabilities to prepare for launch is that a U.S. focus are you, making plans for a qs commercialization as well.
Yes on the first question with regard to European.
Regulators.
You'll be focused a lot of our efforts so far on the FDA.
You were assessing.
The strategic discussions sometimes it comes a when's the right time to approach the.
The email, but we'll be obtaining a country feedback.
As part of that were DTA process.
As we we initiate the studies in the various countries in Europe.
Sorry can you can you repeat your second question.
Well you mentioned in your prepared remarks, you were planning to build commercial capabilities to pair prepare for launch. So I was wondering if that was.
Focused on the U.S. or if you had any plans for X. You asked her here maybe talking to partners are or what your plans were outside the U.S. for commercialization.
Yeah, I think it's a it's a fair assumption that.
Emphasis of what we're doing is on the U.S. you know I think we haven't yet committed about.
I think about commercializing.
Outside the U.S. it wouldn't be a critical to think about having you know ex U.S. partnerships regionally, whether that Asia potentially Europe, but but it's a little early for us to comment on that right now.
Okay.
And then.
For the manifest update that you expect by the ended the year.
What is a key learnings, we should expect to capture from that update.
So oh.
Separately, one will be additional solution that.
We'll have you been mature and enroll.
In in the manifest study across all of the cohorts.
So in particular in arm three a nice lesions, we had a 50 patients that were for 51 patients that were at 12 weeks and a substantial number though isn't it the data cut should be at 24 weeks and so it so again really kind of growing the.
Data set the mature data set that we have a with a significant number more patients to further support the activity of supervisors exam, but but in addition to that we'd been generating additional.
Data Transactionally and you got Patrick to chime in on that to help support the mechanism of action. That's at play here Patrick do you want to just described a bit more about what we plan to a two to present potentially different India.
Yeah, I think too. So has just said we are really focusing understanding based the underlying potentially disease modifying aspects of cpis euros seeks pen and that will come from her that analysis and molecular analysis of.
Bone marrow biopsies with taking from patients prior.
The initiation of treatment and compare those with ongoing three men during the course of treatment and in addition, taking the blood samples from the patients and analyzing them for changes in composition and changes in a gene expression pattern that could explain.
Potentially the been mechanism of action both of these data sets so from clinical samples as well as from ex vivo treat these samples will will update on at the Ash Conference later this year.
Great. That's very helpful. Thank you for taking the question.
Your next question comes from Reena, Benjamin with JMP Securities.
Hi. This is just small Sean for any I know you guys discontinued CPR 12 of five but are there any key takeaways or data points that we should be looking forward to inform us about the easy to program overall when you present, the full prostar data set and do you have a sense of of wind that down.
It will be presented.
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Patrick do you went through that.
Sure.
Yes. So we obviously have taken oldest same funds, we can get out our hands on to analyze from the prototype trial and they are interesting observations that make a want to explore easy it's doing he'd be says in prostate cancer further.
And we put obviously leverage these molecular data that we have a pain from Prostar to guide our future.
Element to it but in prostate cancer.
From from Matt disclosure perspective, we haven't made internally that that decision to win all way exactly we would disclose that.
Pro studied it and how you view that the study as such has not yet in close so.
It's potentially at the later and when that study closes.
Perfect.
And I guess just one other question up what are your some of your thoughts regarding the evolving competitive landscape and math and in particular, what about any other bet inhibitors that are being developed either alone or in combination with Brooks.
Yeah, I'll take that when so in terms of I think your second or your question first in terms of other debt. If there is this is a class of.
Molecules that has been extensively.
Studied by a variety of company in and what we think is unique is that Cpis. Your 610 is.
Based on some of the properties and the molecule we have a very flexible therapeutic window. That's allowed us to progress this molecule to the stage that we have we haven't yet seen evidence from from other editors that seem to be.
Equivalent to.
Yes, there were six that.
Having said that I think subsequent to some of the disclosures that we need publicly around the activity that we've seen in myelofibrosis, we do know.
A couple of other folks have tried to.
Following her pad and ER and there are now you at least two that enters that are being ready.
In in.
But the early in their they're just getting going and perhaps not even yet dosing in patients and so as you think about kind of from a timing perspective.
We're in the door step of starting or phase three study you know, we're simply because by the molecule. He just sobi studied in phase one to establish their safety, there's there's quite a bit of distance to cover their interest in understanding that the therapeutic window as well as a single agent as well as a combination therapy.
With somebody had been hit the pitch that are being studies. So we feel pretty comfortable that we've got a substantial enough lead that but that continues to you give us an advantage even if those are able to identified therapeutic windows.
That that we have which were just a little bit question.
And then in terms of.
Again I.
Other modalities you know, there's there's certainly I think.
Evolving, but but we haven't seen.
From the latest or kind of public data presentations at.
And we haven't seen anything that that's really jumped up to us that is significantly competitive with Cpis recent clinicals point, particularly.
Additional data in the frontline setting.
No we haven't seen any other company present data in that context in the in the Jack experienced patient population. There certainly several other mechanisms that are being studied.
Either single agent therapies like other JAK inhibitors or therapies in combination with.
With Ruxolitinib and there's a variety of data out there that better.
Intriguing, but still unproven.
And we'll continue to monitor those fall.
Great. Thank you very much that was very helpful.
And again, if he would like to ask a question. So please press star then the number one on your telephone keypad.
And at this time there are no further audio question well now turn the conference back over to Checker for closing remarks.
Well take thanks, everybody for who the time today really appreciate the great question and look forward to additional conversations Lasik I think very much and we can we can disconnect warning.
Okay.
And thank you. This concludes today's conference call you may now disconnect.
Okay.
Okay.
Okay.
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