Q1 2021 Cara Therapeutics Inc Earnings Call
[music].
And welcome to carve out Therapeutics first quarter 2021 White line showed results conference call on for.
The sponsor backed out he said on the boat.
The big question and answer session.
Please be advised that this call is being recorded that God rest of your question I would now like with article the other did the car T. Please proceed.
Good afternoon. This is Jack <unk> Smith with Stern Investor Relations and welcome to Cara Therapeutics first quarter 2021 financial results and update conference call.
The news release became available just after four P. M. Today and can be found on our website at www Dot Cara Therapeutics dotcom.
You May also listen to a live webcast and replay of today's call on the investors section of the website.
Before we begin let me remind you that statements made on today's call regarding matters that are not historical facts are forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.
Examples of these forward looking statements include statements concerning the expected timing of the data readouts from the company's planned and ongoing clinical trials the potential results of ongoing clinical trials timing of future regulatory and development milestones for the company's product candidates, including the company's projected.
Timeline for FDA review and potential approval and commercial launch of course is the injection for dialysis dependent CK D. E. P. The expected time line for conducting meetings with the FDA concerning the company's product candidates, including oral of course to use us for N D. D. D D E P.
A D E P. The potential for the company's product candidates to be alternatives in the therapeutic areas investigated the potential impact of COVID-19 on the company's clinical development and regulatory timelines and plans and the Companys expected cash reach.
Such statements are subject to risks and uncertainties actual results may differ materially from those expressed or implied by such forward looking statements.
The risks are described more fully in Cara therapeutics filings with the Securities and Exchange Commission, including the risk factors section of the company's most recent annual report on form 10-K, and its other documents subsequently filed with or for new furnished to the Securities and Exchange Commission. All forward looking statements made in today's call.
I'll speak only as of the day on which they were made Cara therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist. After the day on which they were made.
Participating on today's call are Dr. Derek Chalmers, Cara, President and CEO and care of Chief Financial Officer, Thomas Reilly I will now turn the call over to Dr. Chalmers.
Okay.
Thank you Jack good afternoon, everybody.
And thanks for joining us on the call. This afternoon.
We have continued to make very important progress across our Christian of of development pipeline in the first quarter of 2021.
Culminating with the FDA acceptance of our first NDA filing for our lead product candidate pursuit of of injection.
With priority review of granted we look forward to Arps, just a target action date of August 23rd of this year.
Our interactions with the F D. A on the NDA review have progressed on schedule.
And through the completion of our mid cycle review No Advisory Committee is planned to date.
With our deferred debt tracking for the next quarter or a commercial license agreement with the for pharma in place. We remain focused on preparation for the U S launch of pursuit of of injection in the second half of this year.
As a reminder, Cara executed a strategic license agreement with free for pharma and the fourth quarter of last year for the commercialization of pursuit of injection and U S dialysis clinics.
We're confident that the force establish you asking that for all of the G sales force.
And relationships with the U S dialysis organizations, both large and small.
Will support increased launch momentum and adoption of pursuit of injection in the U S marketplace.
The financial considerations received on entering into the V for agreement.
Contribute significantly to the current strength of our balance sheet.
Further to the terms of that agreement upon U S regulatory approval for Chris of the injection the company will be eligible to receive an additional $50 million common stock investment and then post launch be eligible to receive payments of up to $240 million in sales.
<unk> commercial milestones.
Turning to ex U S. Commercialization planning we were also very pleased to announce in the first quarter that the European Medicines agency accepted the marketing authorization application for dice out of the Caf one injection for the treatment of pruritus associated with chronic kidney disease in hemodialysis patients.
The E M E will review of the application under the centralized marketing authorization procedure.
Under our 2018 license agreement with V for Fresenius day.
He will be responsible for the commercialization of true suba injection across European territories, with Cara eligible to receive tiered double digit royalty payments based on annual net sales and.
And up to $440 million and tiered commercial milestones all of which are sales related.
The E M as expected to render a decision in the second quarter of 'twenty 'twenty two.
Moving on to progress on our oral pursuit of a pipeline, we recently announced topline results from the care of a phase II dose ranging trial of oral <unk> for the treatment of moderate to severe pruritus and mild to severe atopic dermatitis patients.
The trial was a randomized double blind placebo controlled study designed to evaluate the efficacy on safety of oral pursue the for moderate to severe pruritus and 401 adult subjects with atopic dermatitis.
Patients were stratified across treatment groups by disease severity.
With approximately 64 per cent of patients characterized by mild to moderate atopic dermatitis and approximately 36 per cent of patients characterized by moderate to severe atopic dermatitis.
Patients were randomized the three tablet strengths of oral cursive of point to 5.5 on one milligram taken twice daily versus placebo for 12 weeks, followed by a four weeks of an.
Enact of extension phase.
Well care did not meet the main endpoint in the ITT population and the pre specified analysis, a statistically significant change in the primary efficacy endpoint.
Was observed in the mild to moderate patient population.
Which was evident at week, one and sustained through the treatment period.
A statistically the statistically significant improvement was also observed in the four point responder analysis in the mild to moderate patient population with 32% of pursuit of of treating patients.
Achieving a four point of greater reduction in N. R. S at week 12 versus 19% in the placebo group.
These care results have provided key information related to a defined patient grip that his mouth, the moderate and active dose range, which corresponds to that observed in our previous oral Chris Xu of of CK D Phase two trial and effect size on the registration for point.
Responder endpoint.
From which to design phase III trials.
With that in hand, we plan to conduct in the end of phase two meeting with the FDA to discuss the clinical path forward with the goal of initiating a phase III program for oral cursive in mild to moderate a D patients by year end.
We also the plan to present additional data analysis from the care trial at an upcoming medical meeting.
Moving on to our program in pre dialysis <unk> patients with moderate to severe pruritus.
We have previously reported positive top line results from our 12 week phase two trial evaluating the safety and efficacy of the three tablet strengths of oral cursive I'll point to 5.5 on one milligram.
Once daily and identified the one Meg tablet strength to take forward into phase three.
To that end, we recently conducted an end of phase two meeting with the FDA with the goal of defining of phase III program in pre dialysis <unk> patients, which would allow us to leverage the substantial clinical efficacy and safety dataset, we've compiled with cursive of injection in hemodialysis.
Genesis patients.
The FDA has indicated the viability of stage five pre dialysis <unk> patients as the population for our phase III program and also indicated the potential to use data from our previous trials of pursue the injection in dialysis patients to support an approval based on a single phase.
The three clinical trial.
We believe this approach could be could provide an expeditious path to an NDA for oral cursive on pre dialysis <unk> patients and we currently plan to initiate our phase three program by year end.
We also plan to continue our discussion with the agency on the potential inclusion of earlier stage CK D patients and the same program.
Before moving on to our ongoing trials with oral Chris Suva, let.
Let me remind you that Judy the ongoing COVID-19 pandemic and in accordance with the Fda's updated guidance for conducting clinical trials, we have implemented numerous clinical and operational measures to prioritize the health and safety of patients our employees and study investigators and to minimize the potential.
The disruptions to our ongoing clinical studies.
Judy <unk> to the entire carat teams continued dedication and hard work.
We remain on track to meet our main clinical and regulatory goals for the year and continue to enroll patients across oral care suite of the trials.
Moving on to our program in patients with primary biliary cholangitis, we're conducting on ongoing proof of concept phase II trial of oral pursue the in PBC patients with moderate to severe pruritus.
As pruritus is a common symptom of call of static liver diseases 20 to 30 per cent of patients experience pruritus, including up to 70% of patients with PBC.
Our 16 week trial is designed to evaluate the safety and efficacy of the one milligram tablet of oral crisil of I'd taken twice daily versus placebo. The primary endpoint is the change from baseline of the weekly mean of the daily 24 hour of worst itch <unk> score at week 16.
We aim to report topline data from this study in the second half of 2021.
Finally, with the goal of further establishing the broad antipruritic applicability plagued the ability of pursuit of across patient populations.
And underlying pathologies, we recently announced the initiation of a phase two POC trial of oral pursue the for the treatment of moderate to severe pruritus in patients suffering from Natalia pyrostat acre of narrow of disorder characterized by chronic pruritus in the upper middle back.
It is estimated the chronic pruritus affects up to 13% of the U S population and about 8% of these patients suffer from neuropathic edge, including the intelligent parenthetically.
There is currently no well defined treatment of N P and convention of treatments, such as anti Histamines and topical steroids.
Largely in effect of so the remains of significant opportunity for oral because of as a novel therapeutic approach here.
And I'm happy to report the best trial is currently enrolling very well at over 20 active sites in North America.
So overall, our progress through Q1 and recent months has laid the foundation for a very significant second half of 'twenty 'twenty. One we very much look forward to the projected approval on commercial launch of cursive of injection with a strong balance sheet, we're well positioned to support.
Our goal of initiating our phase III programs in both atopic dermatitis and pre dialysis <unk> patients by year end as well on continue to progress our ongoing phase two trials in P. B C and N P patients and we look and we'll be updating you on all of the probe.
Across each of these programs in the coming quarters.
So with that let me turn it over to Tom to detail the financial results for the fourth quarter of the issuer.
Sure.
Thank you Derek as a reminder of the full financial results for the first quarter 2021.
Can be found on our press release issued today after the market closed.
Cash cash equivalents of marketable securities.
At March 31 2021.
Total $228 3 million compared to $251 5 million at December 31, 2020.
The decrease in the balance resulted from cash used in operating activities of $23 7 million.
Partially offset by proceeds of zero point $7 million from the exercise of stock options.
For the three months ended March 31 2021.
Net loss was $23 3 million or <unk> 47 per basic and diluted share.
Compared to a net loss of $28 9 million for 62 cents per basic and diluted share for the same period in 2020.
Total revenue was $1 9 million for the three months ended March 31 2021.
Compared to $8 1 million during the same period of 2020.
Revenue of $1 9 million during the three months ended March 31, 2021 related to the milestone payment.
The company earned for Mariucci pharmaceutical companies first initiation of a phase III trial for Uremic pruritus in Japan.
The company recognized $8 million of revenue during the three months ended March 31 2020.
Which related to license fees earned in connection with the agreement with the for Fresenius medical care renal pharma.
Research and development expenses were $19 one for the three months ended March 31, 2021, compared to $33 5 million in the same period of 2020.
The lower R&D expenses in 2021.
We're principally due to a decrease in costs associated with clinical trials.
Partially offset by an increase in payroll costs and an increase in stock compensation expense.
General and administrative expenses were $6 4 million for the three months ended March 31 2021.
Compared to $4 6 million in the same period of 2020.
The higher G&A expenses in 2021 were principally due to an increase in stock compensation expense and payroll costs.
Other income net.
Net with zero point of 3 million for the three months ended March 31, 2021 compared to $1 million in the same period of 2020.
The decrease in other income was primarily due to a decrease in interest income.
And a decrease of net accretion.
Income, resulting from a lower yield on the company's investments in the 2021 period.
Now turning to our financial guidance.
Based on timing expectations and projected costs for current clinical development plans.
Cara expects that its existing unrestricted cash and cash equivalents and available for sale of marketable securities.
As of March 31, 2021.
We will be sufficient to fund our currently anticipating operating expenses and capital expenditures into 'twenty into 2023.
Without giving any in fact any potential milestone payments.
For potential product revenue under existing collaborations.
I will now turn the call back over to the operator for Q&A.
As a reminder to ask the question you will need the breasts are one on your telephone to withdraw your question. Please press price per pound key.
Standby letter of the compiled the Goodnight rights there.
Okay.
Your first question comes from the line of Greece Howerton from Jefferies. Your line is now open.
Hi, Thanks for taking the questions.
I guess the the first question would be just with respect to the course Hoover injection.
Is there any CMC site inspection or anything like that debt.
Debt, we should be aware of that could be potentially gating going into that produce the date.
And then the second question was with respect to the oral CK the Ah trial.
Just maybe if you could give us a little more color on how we should think about the stage by patient population specifically.
How does that relate to drug effect and variability in the and perhaps you could put that in light of the the recent atopic dermatitis results as well so thanks so much.
Great. Thank you Chris So so on the first question on the site inspection of I do understand that's been an issue for a number of.
Moving Padilla for days in the last few months, but today, we don't know of any indication there's any issue in relation to site inspections. So.
As I said in the and the summary of where we're on track for that produce the date of August 23rd.
Yeah, and then on the oral CK D.
And the population moving forward there so.
Youre correct. So so pruritus as more well defined in the later stage CK of D patients such as such as stage five in fact, if you look at the the prevalence rates and pre dialysis stage five patients is very similar to.
To that end hemodialysis patients. So so we do see this is a population that should respond very well to oral pursue the.
Furthermore.
Using that population, we also think the stage for patients.
Should and could be incorporated into that as the vibe viable population for the same program.
As we believe these advanced stage for patients are eventually transitioning.
To stage five.
Presenting with the.
A higher degree of of pruritus.
So is the patient population the looks very similar to the H D.
We understand how that makes sense in terms of referencing the safety database, we've already seen them and establish with pursuit of injection in hemodialysis patients.
On the advantage of focusing on the population is the F. The year's acknowledging.
The there's there's the possibility of moving forward with a single phase III trial. So so overall on as you know it's been a major goal for us to obtain a label for oral Chris of.
Pre dialysis patients as expeditiously as we can overall, if we focused on on that group it should be possible to have the smaller focused phase III registration program for.
For the single pivotal trial, and we should be able to complete that on a shorter timeframe.
Yeah.
That answered the question Chris.
Yeah.
Yeah.
I guess, if I may maybe just sneak in a follow up here. So if you wanted to include the earlier stage patients into the program as is maybe one idea that you include them in any kind of open label safety study and at or where it would it be more towards.
The efficacy focused study for those earlier stage patients.
Yeah, well it could be both actually true.
Interest because from a logistical standpoint, it's likely we would require a proportion of our patients to be in stage for us are going to be transitioning and to stage five just to get on long enough exposure for.
For the long term safety groups are so so it could be both both on the efficacy of efficacy side on the safety side, we're including stage for we'd like to include stage for patients and as I said, we're continuing that discussion with.
With the FDA with the idea that we'd like to see both for and five in the final phase III program.
Yes, okay very good well thanks, so much for taking the questions Derek.
Thanks, Chris.
Thank you. Your next question comes from the line of Baby Absalom from Piper Sandler Your line is now open.
Hey, Thanks, So just the comparable.
First.
On the I V.
And I realize this is the heart of our product, but can you glean anything are there any learnings from the experience of <unk>.
Yep.
Yes.
Okay.
And all of the.
Cash rents today.
For now.
Uh huh.
Et cetera.
Alright.
Yes.
Right.
Awesome.
The call is.
Possibly.
Okay.
Perfect.
10% or below 10% threshold and is that something that's pretty standard of something that the FDA will accept as the definition of the thresholds for mild to moderate.
David I don't know if you're on the cell phone of it was a very terrible line, but I think I got the suggests that both your questions I'll start with the latter one.
On on the care.
Data on our proposal to move forward on the mild to moderate a D population, which is I think what you were asking and that definitely.
The nation, we've used there is indeed of standard definition.
For the agency mild to moderate would be of BSA.
Of less than 10 and moderate to severe.
It would be 10 or greater sometimes with the addition of an Iga designation.
For two and three being mild to moderate and then for being severe so that is the standard Def.
Definition and accepted.
Regulatory.
Find group for a nice you know we.
We certainly have many drugs out there on them that are defined as used in mild to moderate atopic dermatitis patients for that.
That is standard on the first one I couldnt quite make out of everything you said, but I think youre asking them. If we can glean anything from the experience with possible of.
In relation to hemodialysis patients on pricing.
And.
And the success in terms of uptake of possible.
Look I think we kind of discussed this before in terms of the differences between.
The two drugs.
Being the first to go through to DARPA.
And the and that was on post topper to depth of reimbursement.
POS of Bev was reimbursed at a price of approximately $17000 a year.
On a really on additional calcium emetic drug they were on.
Already oral generic equivalents out there.
But this is an IV drug of its given three times a week. If you look at the population where the rest parathyroid dysfunction.
It's approximately the same size as the population we are addressing with tresiba injection of approximately 30% to 40% of the hemodialysis population and there was a very fast adoption, presumably because of ease of use of parse a bit of an in its first year and I think that was the drug.
The command at round about $300 million in sales and up to over half a billion and the second year. So so we think possession on for US is actually better and that we're a first in class breakthrough medication for the primary symptom for hemodialysis patients that really.
There are no alternatives. So yeah, we have looked at that and thought that could be a reasonable.
The surrogate for the potential we could see with cursive of injection in that population now I think that was your question, but if a picture of our bronc. David then then let me know.
No that's perfect and I apologize for the bad connection.
Yes, no problem. Thanks for the question.
Thank you. Your next question comes from the lineup Annabel Sammy Sammy from Stifel. Your line is now open.
Hi, everyone. This is Nick on for Annabel, Thanks for taking our questions.
Just building on Chris's question about the per dialysis population I guess, we kind of expected stage four to five patients to mostly beyond hemodialysis at that point.
So can you give us a sense of how many patients that's applicable for and where there any data cuts on the phase two that you looked at it specifically in this population.
And then secondly.
Can you help us think about the world for Super label going forward from this point. So of you use kind of of stage by pre dialysis population and the.
It goes on the label will that relatively specific population the limit.
<unk> for of course, you for to get.
On.
The broad Antipruritic label. Thank you.
Great. Thanks, Nick.
I think of is for questions, but let me see if I can remember all of those but.
In terms of the pre dialysis patient population the.
Prevalence rates for late stage, that's four and five patients is approximately <unk> seven per cent. So that's roundabout 2 million patients in the U S. B.
Based on diagnosed <unk> patients of minority of these would be stage five.
And the median time of patient would remain and stage five before transitioning.
The two dialysis is a little under one year.
So so the are in stage five.
For a significant amount of time and as you know there's no approved therapies and it's clearly a significant unmet need in fact, the rates of pruritus, we see in stage five patients.
And late stage for patients is actually very similar to those we see in hemodialysis patients. So there's a very significant.
The unmet need and in terms of looking at the.
These particular stages in our phase two dataset.
We have looked at that.
And based on our phase II data when we look at.
On the analysis of our and our S change in stage three patients. So that's obviously the earliest stage III <unk> III b.
Versus the data we're seeing on stage four and five we do see a much greater effect size in the later stage patients, perhaps not surprisingly they have the more severe pruritus in fact is.
On Mena and our S change, it's approximately 30 points on late stage subpopulation for US is approximately 50% with that in the very early stage III patients. So so theres certainly as data we've already generated the that is the most sensitive patient population pre dialysis.
In addition.
And importantly, because as you know we looked at that quite carefully and our phase two C kit the study the placebo rate.
Is much lower on the stage four and five patients.
And again, we may expect that they have a more consistent for.
Writers are of a higher degree than these earlier stage three and three be patient. So so the advantage here is moving of trial through and potentially stage four and five patients is we'd have a larger effect size and we've already established a more controlled.
The expected placebo response and that and of course, we can use this data and for.
Thankfully all of us enough data to make sure. We can we can power the phase III registration trial for significance on the responder endpoint. So I think those of all.
Significant advantages of proceeding based on you know stage five and as we're in discussions right now including stage for in that patient population and that in itself would be.
You know a significant label that's a large opportunity there for the drug.
And again, perhaps the biggest advantage of non approaches.
Is the timeline. So if we can move there with a smaller trial again potentially one phase III registration trial, and we can access of already established safety database in hemodialysis patients.
That's going to be.
The most expeditious path to of label.
Did that answer all four of them net debt M. S N us on there.
No I think you hit everything thanks for thanks for handling all of the questions and thanks for the clarity.
Yes, thanks for the questions.
Your next question comes from the line of Jason data, Derek Barbie of backup on the hair Guy Your line.
It is now open.
Hello. Good afternoon. This is true.
<unk> on for Jason Thanks for taking a question.
I guess may be the first line chess a follow up of clarity sounds like the FDA had except stage five as a viable patient population and youre in discussion to incorporate stage force, we hate the patients into the phase III program as well.
Got it.
It's day three startups out of the question right now based on the commentary.
And then a follow up on that would be you know.
At the understand correctly, all commercially you're alluding true that doctors you know the the line between faithful stage five of its Barry.
Barry Glory in such a way that you can kind of get approval in stage five you can't elaborate doctors, taking in stage for patient less low I.
I guess my second last question what the.
Can you talk about how.
Often these patients stage five fluctuate between pre dialysis and post the outlets.
And how should we think about startup of the commercial lifecycle of between all of our of course through violent the items of course is that in this particular set of population. Thank you.
Okay. Thanks, Thanks for the questions.
So.
So in order then youre correct. So so the FDA has indicated.
Sure.
In terms of moving forward with the phase three program.
We can certainly do that focused on stage five patients.
And again the of indicated there's the potential there to use data from our previous trials and dialysis patients to support that approval and that was that was going to allow us the leverage as you know over 1500 exposures in dialysis patients and the second major advantage would be approval based on a single day.
These three so we are in discussions and you are correct. When you look at the.
Incidence of pruritus and degree of pruritus and stage four and five is actually quite similar.
And that's going to be part of our discussions with the agency and further defining that patient population the characteristics there.
That is quite different than the very early stage three and three be.
So at this point in terms of the finite the degree of pruritus and how that relates to if you like quality of life burden for the patients and there are certainly two distinct if you like populations there and our current strategy is to focus on the for the five so ultimately we'd like to see both of those.
Stages on the label is.
It's true that patients transitioned from particularly of late stage for and to five.
The relatively.
Defined manner, and then as I said earlier patients would remain on stage five.
Pre dialysis.
On the median range somewhere around just under one year.
So there is of significant.
Treatment period there.
For which oral Chris over would be applicable another advantage and looking at net commercially of course as we would be capturing if you like these pre dialysis patients.
Earlier in the treatment cycle and of course as the move to hemodialysis the denby candidates for pursuit of of injection.
As the move through the dialysis stage of the disease. So right now I think we have a defined path forward. We can explore on stage five we'd like to further expand that population at this stage for thinks it it seems to make sense. When you look at the characteristics of pruritus in those two ste.
Ages.
As I said earlier, we have good data from our phase two dataset that we understand the placebo there theres a large effect size and we could have high confidence we should see oral cursive of efficacy in that particular patient group.
Did I get the epicenter Chi.
Yeah got it alright. Thanks, so much Nathan just one follow up for me just for confirmation that the.
Location on stage for stage, five and or stage force for.
Pre dialysis patients.
The reimburse differently and it will not be.
Part of the CMS bundle of put that payment cuts of duration do I have the correct.
You have that correct chi the pre dialysis <unk> patients would not be part of the ESR the bundle.
Awesome. Thanks, so much.
Shape.
Your next question comes from the line of Joseph Stringer from Needham <unk> Company. Your line is now open.
Hi, everyone. Thanks for taking our questions all of them.
Switching off of going to go with PBC pruritus, the phase II readout.
Coming up on the second half year of.
Maybe help us.
Understand or at least maybe set some expectations around the data readout.
And specifically the PBC patient population as it pertains to the the three point.
Responder analysis, how how similar would you expect.
You know, maybe placebo response rate or exercises relative to <unk> or <unk>.
And this trial thank you.
Thanks, Thanks, Joy and thanks for the question on PBC.
Of course, I think you remember one of the main reasons. We've we've initiated our oral care suite of of trial in that particular patient group is that says the patient group for which.
The older <unk>.
Kappa agonist now fewer for units.
Approved in Japan has received the label extension. So so we have high confidence confidence that the mechanism itself that is Kappa agonism.
Should be effective in relation to liver disease related per.
Writers.
The other aspect of going after of PBC, It really relates to consistency and the pruritus. So there isn't a great deal of data there in terms of pruritus trials there is one.
The set of data from now fewer of fine.
It seems as though the placebo was quite well behaved.
And liver patients.
But with us more consistent pruritus, we see in PPC up to 70% of patients have moderate to severe.
We do expect that placebo rate to be more controlled and not particular group.
The issue with placebo rates seems to relate to the liability in early stage patients as we saw on <unk>.
Fluctuating.
And that can offset the placebo response and lead to false positive. So we do expect the based on the data the sat there.
In terms of on older Kappa agonist that that placebo response will be much much more behaved in the end of PBC patients.
Did I get that Joanne.
Alright.
Thanks for taking my question.
Thank you.
Your next question comes from the line of all ran on Loopnet from HC Wainwright. Your line is open.
Thanks can you hear me.
We can hear you arm Oh, great I appreciate it.
I'm, sorry, if I'm not fully understanding some of the language you're using so just maybe you can make it more explicit with regards to the oral <unk> program going forward.
And the choice of language stage five was that you said the FDA will allow you to do that or accept that is that something that you pushed for that the FDA requested.
So specifically what we were interested on when we went there was the idea that we could leverage our hemodialysis program with pursuit of of injection. So there. We wanted to access that safety database. We wanted to propose since we had already established efficacy in hemodialysis patients with two large.
<unk> phase III programs that we proposed that we should have a single registration program.
To obtain the label that the FDA has indicated that that program could work. If it's focused on stage five patients as I said earlier, we understand stage five look very similar to hemodialysis patients in terms of the frequency.
The prevalence of the pruritus and the degree of pruritus.
And they've also indicated that they would allow us to to use data from our previous trials and dialysis patients and they look at approval based on a single phase III trial. So that was the response from the agency out of responses that stage for patients.
Really look very similar to stage five the their degree of pruritus the prevalence of pruritus. There. So our proposal is somewhere in the dialog on that somewhat further defined on the characteristics of for.
With the five <unk>.
Is that that program should it should include both the stage for patients on stage five so the agency is acknowledged the strategy for stage five our dialog continues as we wanted to include stage for some I understand you correctly. The primary the imperative was to use IV data tier.
The advantage and they said sure if he used stage five and youre trying to broaden that a little bit.
Yes, Okay, Okay, Great and then and then if I can follow up.
Are we sure of that one phase III then if you move forward, let's say in stage five alone just to keep the conversation simple what's the feis or is there other some other variables with regards to drug effect size or of safety out of that study that will you know down the road determine whether one or two phase III the unnecessary assuming at work.
Statistically well again I think we are of a high degree of confidence based on our phase III data we already have this.
If you liked subgroup analysis.
On late stage stage four of five versus stage III is the bigger effect size of placebo is more controlled so.
So we have.
High confidence is that slightly cursive.
We'd have significant efficacy on the late stage pre dialysis patients. So yes at the minute they've acknowledged if we concentrate on stage five of there'd be a path forward.
For a single phase III trial, we'd like to expand that to include stage for in lots of dialogue that's continuing.
Okay, and if I may I apologize just.
On dosing in stage and phase two you settled on the after phase two you settled on the highest one milligram dose that was low including our population of cross stage three to five so if you move forward in the stage five of late four to five how confident of argue that you have that one milligram is the right dose still given that that theoretically at the different <unk>.
Average level of impaired.
Impairment renal impairment in that population.
Right. So so.
If we look at Mena and our S changed which as you know is the most sensitive of endpoint of the continuous endpoint, we consistently use on our stage two dose ranging in the later stage patients the stage four and five and I mentioned this earlier, we do see of larger effect size.
On the effect size there is in the region of 30 30 points.
And the earlier stage patients that effect sizes.
Approximately 50% of that so we already have the good data in hand from our phase III trial, the mm Theres, a large effect size with cursive in that late stage population with the golf.
So comfortable of the safety profile of that dose.
We are we are comfortable with the safety profile.
Okay, great. Thanks for the clarification I appreciate it.
Thanks Arne.
Thank you there are no further questions of this time turning over the back to you for.
Polymers.
Great. Thank you Jerome so thank you everybody for participating on the call today.
I'd also like to thank the Cara team our study investigators and most importantly, the patients who continue to participate in our clinical trials and we look forward to updating you again very very soon have a have a great evening. Thank you everybody.
Yes.
Ladies and gentlemen. This concludes today's call. Thank you again for your participation you may now disconnect have a great day.
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