Q3 2020 Constellation Pharmaceuticals Inc Earnings Call
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And welcome to the constellation Pharmaceuticals third quarter 2020 earnings conference call. At this time, all participants are not listen only mode. After.
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I would now like Santa comp in C.S., because today, Kelly Boyer Vice President of Investor Relations and Communications. Please go ahead ma'am.
Constellations third quarter, 2020 financial myself and operational performance.
Participating in our call. This morning, I kick out we thought that constellation Chief Executive Officer, Dr. Katz, Humphrey I Chief Medical Officer.
Dr., Patrick Trulia, I, Chief Scientific Officer, and lastly, I Chief Financial Officer.
Please turn to slide 10.
Before we begin I Wanna Quintette that our presentation. Today will include forward looking statements, which are subject to take on risks and uncertainties actual.
Actual results may differ materially due to Danny it's important factors, including those described in the Bakken section as well as a discussion of potential with.
Second tier.
Important factors in the company's most recent filings with the Securities and Exchange Commission, including the company's quarterly report on form 10-Q for the quarter ended September 32020, which we filed earlier this morning.
And now I will turn the call over to kick out.
Thank you Keith and good morning, everyone.
Please turn to slide three.
Let's begin with an overview of constellation.
We're building a fully integrated pharmaceutical company.
Who started discovery with the advancements that we need with a preclinical and clinical programs all of which are home grown we now have a pipeline that we believe sustainable.
The next step for the company is to launch and commercialize your own therapeutic.
As for how this translates into what we're doing right now.
We aim to get Cpis, you're seeking to transform the standard of care in myelofibrosis would it potentially disease modifying therapy.
We're also working hard to deliver a potential best in class you teach two inhibitor therapy to expand the addressable patient population with the predicts against that target.
And you're also continuing to invest in novel and impactful hematology and oncology therapies with our discovery platform.
All of this is made possible by the strong team that we have built and you're continuing to grow it to take constellation to the next level.
Turning to slide four please.
Today, you will hear updates about Cpis your 610, Cpis year 209 for revenge and keep our.
Our Chief Medical Officer, Jeff Humphrey will recap, what you've seen so far come Cpis are six can you benefit study as well as what we're gearing up to present at the upcoming Ash medical meeting in a couple of weeks.
In addition, Jeff will review with you the details behind the Phase three study that we will see me machine.
Patrick Troyer, our Chief Scientific Officer will tell you about our plans for C.T., I'd or TV or night, which we believe to be a best in class and teach to inhibit you.
He will show you some of the science behind the compound and how that translates differentiated development opportunities.
Beyond this we have a robust preclinical pipeline, which we will talk more about the upcoming months.
Turn to slide five.
On this slide I'd like to remind you that we believe Cpis. Your 610 has the potential to be a disease modifying therapy.
We've all been very focused on Cpis years, 610 impact on spleen volume reduction in symptom improvement and we're very pleased with the profile that weve seen others measures.
But we're also excited about presenting translational data at the Ash medical meeting.
To highlight the improvements that we are observing in red blood cell biology anemia in bone marrow fibrosis will.
<unk>, we believe that this would measure shown here taken together point to the potential for disease modification <unk>.
With that I'd like to turn the call over to Josh.
Thanks trigger let me review data, we've presented to date on Cpis 610.
Please turn to slide six.
Manifest as our phase two trial of Cpis six pen in patients with myelofibrosis.
An arm three cpis six tenants given in combination with Ruxolitinib in patients with JAK inhibitor naive first line disease.
In arms, one and two cpis six tenants given as monotherapy or as add on to Ruxolitinib in patients the second line disease.
I'm pleased to say that I'm three is completed accrual at approximately 80 subjects. Please turn to slide seven.
This slide shows key preliminary data from on three that motivated us to start a phase three trial.
In arm three JAK inhibitor naive patients receiving 610, plus ruxolitinib experienced consistently high spleen volume response rates overtime.
The 24 week SCR 35 rate was 67% and 63% in the first 15 and 30 evaluate both first line patients respectively.
These rates of spleen volume response compare favorably to historical rates of 30% to 40% in prior randomized trials of Ruxolitinib.
Please turn to slide eight.
Here's a summary of the safety profile reported and arms Threed. The on target toxicity of both C.P.I. 610, and Ruxolitinib. His thrombocytopenia as you can see here the rates of grade three or higher are relatively low and we believe that the combination is generally well tolerated.
Please turn to slide nine.
[noise] preliminary data for 610 monotherapy and combination therapy in second line Myelofibrosis, where also promising.
In cohort one be second line patients receiving Cpis 610, as a single agent demonstrated an SVR 35 response rate of 24%.
<unk> rate significantly higher than other agents in the second line setting.
In addition, transfusion dependent patients in cohort, one a and two a achieved 21% and 34% rates have come for conversion to transfusion independence, respectively.
We believe that the data for Cpis 610, which include reductions of spleen volume improvements in total symptom scores conversions to transfusion independence and changes in bone marrow fibrosis at 24 weeks, our preliminary signals of a potential disease modifying effect of Cpis 610.
Please turn to slide 10.
We will be updating our data from manifest at Ash 2020.
Please note that the abstracts to be published in November will not contain new clinical data the new data will be presented at the ash meeting itself in December.
New 24 week data for arms, three and arm to will be discussed in separate oral presentations on December 5th by doctors, John masquerading as a search for stop SEC, respectively.
We will also present three posters on December six and seven.
One poster will discuss new 24 week data in arm one.
A second poster will discuss translational data, including 24 week changes in bone marrow fibrosis and cellular therapy from patients enrolled in manifest.
And trials in progress poster will discuss the design at Mannafest two.
The new data will also be reviewed at an investor event.
With discussion by key clinicians on December 7th.
Please turn to slide 11.
Our experience with 610 continues to grow.
The dataset at Ash for Cpis 610, Ruxolitinib in first line Myelofibrosis will include 24 week data for approximately 50 to 60 patients.
The dataset at Ash for 610 monotherapy or as add on to Rux in second line Myelofibrosis will include 24 week data for approximately 90 to 100 patients.
Please turn to slide 12.
The data in first line myelofibrosis support our decision to conduct a pivotal phase three trial manifest too.
As a reminder, the trial is a blinded randomized pivotal study in JAK inhibitor naive patients with primary or secondary myelofibrosis, who have advanced disease with splenomegaly and symptoms requiring therapy.
Approximately 310 patients will be randomized one to one to Cpis 610, plus ruxolitinib versus placebo plus ruxolitinib.
We have begun site initiation activities and remain on track to dose our first patient in the fourth quarter. We continue to be focused on executing this important clinical trial.
And now I'll hand, the call over to my colleague Patrick.
To discuss Cpis zero two zero not.
Patrick.
Thank you [laughter].
Right Slide 13.
And he already has emerged from our internal discovery efforts.
Turning your attention now to another product candidate that stems from constellations oncology research platform. They.
He is doing he does PPI euro to <unk>.
We continue to be excited about the progress of this program in the clinic.
You will recall that you used to is that he's done that I'm trying to frame it.
His role is to try and isolate tonnage three had like 27, and thereby some surprises expression of specific types of gene.
We believe that Cpis your enthusiasm and I has the potential to be a best in class, Yes, do we need to we.
We decided cpis zero nine to improve them first generation is doing here because in a number of ways.
Including increased potency long residence time, and maintaining exposure levels by not using its own mentality.
With that profile, we can pursue a very broad application of each doing condition doubling down on context, but easier just doing that already have shown clinical activity and where do you see it with an opportunity to try go oh, it easiest to cooperate with established on containing private pathway such as in the case.
Prostate cancer.
We are excited to explore whether CPR who's your on line 10.
Thanks, Roy potentially significant leasing relationships re sensitized to chemotherapeutics agents in the context of required for overseas test and reprogram the tumor microenvironment and Dumont sales to promote from one Uni.
Please turn to slide 14.
This slight pricing sales up at coral breaks the three key properties of Cpis foods, you're aligning that supported basic cost potentially increased potency local residents fun and lack of induced mentality.
The table on the left.
Illustrate the superior biochemical potency of Cpis, North, Louisiana, nine compared to other clinical stage two inhibitors.
The middle panel demonstrates one of the key properties for which we designed.
We need to achieve 24 seven target coverage, because we think that's an important component for driving efficacy.
And as you can see here after the Cpis yours, who's here and I'm biased to easiest to it doesn't come off for extended periods of time, where its first generation. It usually does come off in a matter of hours.
On the right you can see the exposure profile of these guys are.
And I have an orally administered to my office things, though Steve one and maintenance of Cpis Usnine exposure has stated stayed up at 12 days of once daily dosing the 12.
This is consistent with the observation that the company does not induce its own metabolism over the course of treatment.
Its profile, we believe 009 may track for therapeutic potential looking to biology based.
Please turn to slide 18.
This slide highlights some of the content that we are interested in for the initial development of Cpis dealer to dealer line a.
The cartoon on the left illustrates molecular context, what you don't make aberrations creative auctionone payments on easiest to.
Such is gain of function mutations in the easiest way to sell certain certain subsets of the tomo or loss of function mutations and Gary form a call back one such as observed several solid tumor indications.
We continue to be interested in the exploration of prostate cancer, an indication for Cpis numerous was zero nine where we have repeatedly seen functional corporation of easiest way because we pay.
They are all under generally accepted targeted agents.
In addition, we are interested in acquiring properties.
Anything data illustrated but each to the pricing the expression of the SHL Afmeleven gene and Sullivan 11, reactivation repay societies to most chemotherapeutics agents, so by combining cpis who's the overnight with chemotherapy indication what could potentially reverse or prevent quiet.
Resistance.
Turning to slide 16 please.
Now that we have seen the breadth of the opportunity in various context of Tampa genetic let me give you safer. So cpis Europe 2.09 performance in some of those context on this slide we showed eight other cpis north whose eurobank demonstrated superior efficacy in preclinical mouse models on a once daily dose.
It seems schedule.
Enjoying vivo studies Cpis your who's here and I achieved tumor regression in month of both from a commodity cancers with easy it should gain a functioning and patients showing of the liquid and solid tumors with areas. One a loss of function mutation number right.
Its comprehensive easiest to target engagement achieved bites potency long residence time and other favorable profit. These may allow us to target deeper responses and to expand the patient population not adequately addressed by first generation easiest thing.
We are currently facing Cpis there are 209 in a phase one dose escalation study in an all commerce patient population.
We have completed multiple dose cohorts and seen a dose dependent increasing exposure and no EBITDA took induction of component as well.
We have also seen dose dependent increases in target engagement as measured by the assessment of multiple Pharmacodynamic markets. We continue to dose escalate to determine the recommended phase two dose and why we're willing to pay a healthy yet it's still possible that we will reach that phase two dose late 'cause it [laughter].
We are excited at several of our biomarker hypothesis in phase two.
And now I invite the most to take the floor.
Thanks, Patrick Please turn to slide 17, and lets review our financial results for the quarter we.
We had a net loss attributable to common stockholders of $33.8 million in the third quarter, which was in line with our expectation.
The net loss per share was 71 cents in the third quarter compared to 82 cents a share in the third quarter of 2019.
R&D expenses increased by $9.2 million year over year, mainly due to work relates to the city.
Hi, Ted.
The smell costs also increased compared with the prior year quarter as we continue to build out our organization.
Without financing in June our cash cash equivalents and marketable securities were $489.4 million as of September 30th.
Which we expect will fund our operations into mid 2023.
We plan to use these resources to complete both Manocept and medicine to I'll say two M.C. three clinical trial for PPI as 10, respectively.
To substantially build the commercial organization needed to launch the compound.
In addition, our our cash will allow us to complete phase one two clinical trials at the CIO to nine.
Well supported discovery platform.
To conclude we are very pleased with the progress we're making.
We look forward to presenting new data for PPI is 10 at the upcoming Ash meeting.
To start dosing patients in amount of it too.
In the <unk> nine program, we're making progress toward determining the recommended phase two dose and initiating that policies and stuff.
We look forward to giving you further updates along the way on that program.
So with that I'll turn things back over to the operator.
Operator would you. Please now open the line for questions.
Thank you as a reminder to ask a question you don't need to press star one on your telephone.
Let's try your question pest upon key please standby when we compare the candy roster.
Our first question comes from on the Palm Rama with JP Morgan.
Line is now open.
Hi, Thanks, so much for taking my question just two really quick ones. So what is the final gating factors to getting Mannafest, two up and running and enrolling patients later this quarter and a second question didn't see anything in the release today or in the slides on six trend in additional indications like BT.
Maybe just an update there on timelines. Thanks, so much.
Hey, underperform aren't great. Thanks for your questions, maybe I'll just quickly touch on the the second question first and then I'll turn it over to Jeff to answer your first question timing.
Yeah, we are we announced earlier that we are aiming to start a ER.
Each study in essential thrombocythemia.
That work is on track, we're we're going through the protocol writing site selection.
All the work that could operations to happen to start enrolling patients and so we do anticipate being able to do that shortly.
And there may be other indications that fit nicely with some of the my weight biology that we've uncovered cpis years to extend that will also begin to kick off in the next six to 12 months.
And so.
That's that's all kind of is in progress and on track.
Jeff do you want to comment on kind of where things stand with the with the medicare's two initiation.
Yes. Thanks triggered as you know we've listed on clinical trials Dot Gov now the trial design and we're in final preparations at the site. We're very much on track for a second second half start and were very focused on rapid start and execution of manifest too.
Thanks, so much for taking my questions.
Thank you and next question comes from Brian Abrahams with RBC capital markets. Your line is now open.
Yes, thanks for taking my questions and congrats on all the progress.
Since from me if I could first of all I know, there's going be a lot of focus on the clinical data. It asked but you mentioned, there's going to be a poster on translational data for 610.
What should we be looking for there what's how should we think about the bar and how important is that data going to be do you think for.
For earlier stage usage of the drug if it ultimately becomes available.
Yeah, So I'll start with that and then in the media Entertainment and Adam you can add to that.
By the way I would look at the the translational data at Ash extended the because of the first the first of a kind of growing set of disclosures that we'll have over the course of the next several scientific meetings that started to really tie together the clinical effects that we're seeing with the mechanism of action that we believe is.
I play with the logistics and again it comes back back to the MINDBODY biology.
And potential impact on Red blood cell biology.
And so I think the way that the way to think about the the ash disclosure is kind of the starting to come to Peel back the onion a bit more when you talked about bone marrow fibrosis to date.
But we can start to do.
Dig into patient samples.
And look a little bit more closely at the biology.
Type of mechanism together patch.
Patrick would you want to add.
Anything more on kind of how that compares to kind of what we might do in the future.
Well I think you said it will run a clinic the mechanism of action to the clinical benefit that we have seen so as for the ash disclosure I I think we will.
To be able to report on a.
White said, though locally topology reviewed bone marrow fibrosis data.
Across the maintenance is.
Patients.
Subset of these will be a.
Centrally reviews by then and we will also report this ticket sales on a subset of patients for some of the myeloid changes that we have seen in the bone marrow of the patients treated with CP idealistic and.
Yeah, and then Brad just to add to that kind of the second part of your question. There does it help <unk> will be yeah again I think this is the beginning of a growing dataset.
And ultimately we think it will be very important because as we mentioned in the call you'll spleen and symptoms.
Required for regulatory.
The approval, but ultimately you think what through the special about Cpis your competitive potential could modify the course.
Its data like these that will start to allow us to be able to your duty.
Mystery guidance.
Got it and then speaking of symptoms I'm just curious your latest views on a potential powering of manifest to with respect to the symptom score and designing an interim to.
Enable recycling there and I'm also curious it's Richard precedent frozen from other MF drugs changes your view as to whether or not you'd need to hit statistical significance on that end point.
Are you referring to Pacritinib.
Yes.
Yeah, Yeah, just to just to take that I mean, definitely I think an interesting and positive development in the regulatory landscape and we'll be watching it.
Carefully as it unfolds.
And so it's something to keep an eye on.
But but I think our our path that we laid out at the base case.
I'd been and always will be always has been and will continue to be that the phase three design. The belt line and of course, we'll we'll continue to explore anything else that you think it's possible.
No nothing's really changed on the.
How we're approaching the trial design with regard to a power and we've done a pretty good job here with the assumption from the data that we generated as well as a.
Historical data sets to power the study pretty robustly.
And weve given ourselves added flexibility to reply that needed I don't have any more detail today on good though the details of how we would make that decision.
That's for a truly ready.
Got it and one more quick one if I could just squeeze it in on the genome toxicity I know that's something that's seen with other epigenetic modulators like H. stacks and I'm just sort of curious for any additional work around that or changes to inform consent might at all impact the timing of the manifest to start or have any significance for a future label. Thanks.
Yeah. So as you may know to going in there in the queue.
We were going through various TV nonclinical work nothing that we think the impact any any about the timelines that are that are on the critical path and there is certainly more work to do to to understand when you're going to signal that but I think it was pretty.
Pretty normal course, Illinois Patrick.
Patrick with you had a comment anymore on that.
Yeah, we haven't completed the Jena talks packets yet.
I agree with you I think there is nothing at this point that makes us feel like that.
We deviate from the timelines.
Thanks again.
Thank you.
And then next question comes from Michael Rose with Baird. Your line is now open.
Hey, guys. Thanks for taking the question I just had a quick follow up on a manifest to study.
So it seems like you guys are fairly on track to start that soon so I'm just curious if maybe you can share your thoughts around enrollment timeline.
Now that you've had experience with manifest.
Jack you will take this one.
Yeah sure thanks trigger.
Mike, we accrued manifest well I.
We as you know there was slow downturn coated during which we learned a lot and we anticipate that manifest who will accrue.
Well right now we're not currently disclosing expected timelines for full accrual.
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Great. Thank you.
Thank you.
Our next question comes from Biren the men with Jefferies. Your line is now open.
Yeah, Hi, guys. Thanks for taking my questions, maybe just to start on Mannafest. Two can you talk about whether there's still an adaptive design feature in the trial.
And what drivers would lead to enrolling additional patients from the target 300, and you expect to enroll and.
And then I guess, what's overlap in clinical sites for manifest to compare to the phase two study.
Hey, doing how is it going but thanks for your question.
So oh, well first of all I think we've got going on.
Really robust Cabot powering the study however, as to the question that was raised earlier, we've given ourselves flexibility to increase the size, if we think that.
We'll we'll want to do that basically the fact that we are making our powering assumptions for t. It that's on a single.
Single arm study so it's really just to give us the flexibility on that if its needed.
We feel like we've done a you're going to have a pretty good job.
With the with the assumptions that we've made.
So there's no there's no additional kind of information that we have at this point in terms of.
When and how that decision would be made them.
Okay and then maybe on the second line study can you maybe talk about I guess, what you expect your pass to be there how long do you feel that the data at Ash I think you'll have an additional five to 15 patients in second line at 24 weeks.
Do you feel that that would be sufficient to inform you of.
For next steps forward in that indication.
Yes, so we're really really we're really excited about the entirety of the data package that you can presenting around succession in first line and second one.
But we take a careful look at what we think is the right.
Regulatory commercial path forward and at the end of the day, we concluded that the the right.
In a study to do for us would be focused on.
Cuts or registration work yeah in the in the night vision.
Our expectation is that the label that we could achieve would be a broad label that would cover your first.
First and second line patients similar to the label that Ruxolitinib and figure out new path and so we'll continue to enroll patients in.
In the second line cohorts.
The dry publications and ultimately hopefully drive reimbursement.
But but we currently are not planning to do a another registration study in the second line setting.
Having said that we're really excited about some of the results that we've been seeing in that context.
Great. Thank you.
Thank you. Our next question comes from that to her Cannella tourist Securities. Your line is now open.
And investigators that we have a lot of experience with we.
We had 50 plus site.
In our manifest study and we'll we'll end up more than doubling that in.
In that way.
You know they werent space the patient, but there were a couple of patient here and there that they may have missed this the scan.
And so we were able to put together.
Guidance for how to make sure that that data gets collected.
And reported and so in.
And that was a good some good practice with that.
And we will be able to use that yes. If there is you know another.
You know another cold related.
Got shutdowns in the future.
You know there's already has been a good deal of flexibility.
On the number of weeks.
Prior to and after.
The actual date.
Some 24 weeks four to impute to that that time point.
Theres also flexibility on the location of where the data can be collected.
So so there's there's we've worked through that nicely in manifest and we'll be able to use those seen procedures and thats too.
With me today, that's very helpful. Thank you so much.
Thank you. Our next question comes from Kenneth Atkins of Cowen and company. Your line is now open.
Hi, guys. Thanks for taking my questions.
From manifest to do you plan to provide updates in terms of Han enrollment is progressing and in terms of the interim analysis could the the refinancing at that point allow for lowering the target number of patients or are you only able to expand the study at that point.
So together that I think its it doesn't mean, we're not at this point ready to talk about any kind of any interim we're still we're still kind of making final decisions on what to do there and so maybe we can save that for later later discussion.
Got it okay and.
Thanks. Thanks for your question I'll start and then I'll turn it over to Jeff.
Maybe I'll just start by saying that we're going to be learning.
From this study I think that base, what we there is no approved therapy today.
I think the previous studies.
As you inclusion criteria have not really folks.
Focused on what we think are the right type of patient.
And so so we're.
Part of what we're trying to do here is to is to really identify who are those patients and what were what the endpoint.
Would be.
Maybe Jeff you could talk a bit more about that.
And then I can add more about the opportunity then yeah. Thanks, Chick or so 610 has reduction of platelets has one of its one of its effects.
And certainly within essential thrombocythemia patients present with very high platelet counts.
We're looking for a population that is hydroxyurea refractory Wes.
Platelet counts symptoms and the consequences of this disease include symptoms, such as headache, and thrombosis bleeding events and our art.
Our trial would be done to look for a signal of efficacy, including complete hematologic response and response incentives will be looking at things like the MPN assaf.
Thanks.
Yes, we're still doing some work on the commercial side to understand the the the overall opportunity, but we think it could be it could be pretty significant.
Great. Thank you.
Another question on.
If you had any updated thoughts on your ex us strategy.
What your plans are for you study and what factors you are considering in a decision on whether to partner in Europe.
Yes, yes, so I think from a.
A regulatory perspective, we we believe this the study design.
Is the correct study to address.
Approvals globally.
And and we'll execute on it too.
To drive to that.
From so from a partnering perspective.
We don't we don't need the assistance from a global player.
To help us execute on honest on study.
And to get distracted from global approvals.
Commercially I think it's a different question.
We have not yet as the company made the decision to build.
A commercial infrastructure outside the U.S I think it's quite reasonable.
Too soon that at some point that we would.
Seek a partner to help us do that but we have not yet made that decision.
Great. Thanks for taking my question.
Thank you.
Our next question comes from Ren Benjamin with JMP Securities. Your line is now open.
Hey, good morning, guys. Thanks for taking the questions and congrats on the progress winning then I guess just hey, good morning, just maybe two from me can you talk a little bit about what might impact response rates.
Over time as it is it a mix of kind of heterogeneous patients or is it.
Maybe patients overtime, not adequately being controlled and I guess I'm trying to get a sense, how 52 week data might look and how much of that we might see at ash and maybe as a second question and Mannafest two we notice that the the trial includes post the T. and PV patients and so I'm kind of it.
Adjusted to know your thoughts on how these patients differ from primary MF patients and whats your experience been.
For those patients have been treated with the combination.
Yes so.
You know kind of durability of the response to making now will be Scott.
A subset of the patients who had been on therapy long enough that we can start to look at that.
I think it's kind of just kind of qualitatively from what we've been hearing.
We feel pretty pleased about the.
You know the effects that we're seeing from a durability perspective.
And then including also from the durability and seeing from our second line patients who some of those patients working on.
For over three years.
And that and this is in a very thick rich.
Factory patient population study so I think it's fair to say that we can start to.
You examine some of that data at the upcoming Ash update.
I think we are as I mentioned at least qualitatively, so far pretty pleased and as.
And as you start to get more and more experience. We can we can we can start to start to quantify that.
With regard to post the T. and post TV and primary.
Yes, I think we have treated patients of all types similar.
Similar to previous and next studies that have the sales.
Okay therapies.
We haven't seen anything jump out as kind of a major difference in how those patients are responding again the response rates overall at a pretty high.
So not a clear separation in that signal.
From post equals PD in primary enough.
Great. Thanks for taking the questions.
Yeah as a reminder to ask a question you will need to press star one on your telephone. Our next question comes from Jay Olson with Oppenheimer. Your line is now open.
Hey, Thanks for taking the questions I had a few on to a nine.
Can you share any comments on the safety and Tolerability profile that you're seeing in the dose escalation study and then also I think you mentioned the potential for synthetic lethality could you maybe provide some additional color on that hypothesis and.
And then I was wondering what combination with Twonine that you're most excited about and finally.
We'll twonine be developed as a monotherapy or is this a drug that will only be used in combination. Thank you.
So.
I'll start, but also submitted Patrick.
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To help so.
So from a safety perspective.
Kick into the details.
But I think okay kind of implied in Patrick's kind of update there was that.
We we are continuing dose escalate.
And looking to identify the RP TD.
And thinking about the.
The maximum tolerated dose is a key component of that so I think we're doing pretty well from a safety perspective.
You know who in this mechanism they demonstrated with our previous experience a total of five.
Can can be very well tolerated.
And then the synthetic reality.
Kind of context, I think is very fascinating.
You know there there tends to be kind of a tug of war.
On gene expression, maybe Patrick do you want to kind of get you talk about that a little bit.
As well as somebody to questions about combinations and potential from other activity.
Sure, Yes, thanks, Jason So the question so.
Just like we are really happy about the safety profile and the performance of Cpis, Yes is there a nine to date.
We have seen nice dose dependent increases in exposure.
Increasing levels of.
He assessed by multiple Pharmacodynamic markets. Since the study was really designed as an all commerce study to primarily determined.
Safety and TV becomes the comment on on.
You know the particular biomarker hypothesis that be healthy sign for the expansion cohorts in phase two we get.
So in the midst of this study will further dose escalating and we hope that.
Once we get into the expansion cohorts, we can start answering some of the questions that we have built around this area is when a hypothesis as well as some of the other molecular like guidance hypothesis that we have.
You know that we have shown an interesting.
As for other questions regarding the combination so I will.
We haven't completely finalized our expansion plans, yet, but we have plans to open monotherapy cohorts as well as how the combination development plan. So at this point.
I think there are opportunities such as Europe, Brazil, and nine as monotherapy, but also in combination.
Great. Thank you for taking the questions.
Thank you.
Not showing any further questions at this time I would now like to turn the call back over to Tucker for closing remarks.
Well. Thank you. Thank you very much I wanted to thank everyone for taking the time to listen to recall after your question.
I think you've got a very exciting a couple of months ahead of us as we head into ash with.
With that with plenty of new data.
And progress on our execution towards that bringing 610 to fruition for patients as well as progressing our pipeline. So so thanks again everyone.
Everyone and look forward to I talked with you off into.
Ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect speakers. Please standby.
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