Q3 2019 Earnings Call

Good afternoon, and walk into care Therapeutics third quarter, and so that's 19 financial results conference call.

All participants are now in listen only mode.

There will be a question answer session at the end.

Please be advised that this call is being recorded it carrots request.

Now, let's turn the call over the care team. Please proceed.

Good afternoon gene or high end with Stern Investor Relations and welcome to Cara Therapeutics third quarter 2019 financial result in update conference call.

The news release became available just after four o'clock P.M. today and can be found on our website at www Dot Cara Therapeutics dotcom.

You May also this into a live webcast a replay of todays call on the Investor section him for web site.

Before we begin let me remind you that statements made on today's call regarding matter 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 completion and announcement of the results of our ongoing clinical trial.

We expect the tiny in design of our planned clinical trials.

Future regulatory and development milestones for our product candidate.

Companies projected timeline for this mission of its first India.

The potential for theory for five to be a therapeutic option and multiple prey to syndication.

Besides of the markets that are potentially addressable by a product candidates and are expected cash breach.

Because such statements are subject to risks and uncertainties actual results may differ materially from those expressed or implied by such forward looking statements.

Risks are described more fully and Cara therapeutics filings with the Securities and Exchange Commission, including the risk factor section of the company's annual report on Form 10-K for the year ended December 31, 2018, and its other documents subsequently filed with or furnished to the securities and Exchange Commission.

Participating on this call are Dr., Derek Chalmers care, President and CEO and Dr. Mani Mohindru, Chief Financial Officer, and Chief Strategy Officer, I'll now turn the call over to Dr. Chalmers.

Thanks, Jane and good afternoon, everybody and thanks for joining us on today's call.

So we certainly realized significant progress across our clinical development pipeline this quarter.

In recent months, including an expansion of our oil pursue the clinical program into two new putted credit patient populations with high unmet need you topic dermatitis on chronic liver disease associated pruritis or C.L.D.A.P.

We've also advanced our phase two trial oral cursive, a known hemo dialysis patients with chronic kidney disease associated provide us with CKD Pete.

Well, we're on track to report top line data before the end of this year.

And lastly, following a recommendation from the independent data monitoring committee or Idmc, we increased the target enrollment of our second pivotal phase three trial of pursue the injection and hemo dialysis patients with Sicad D.A.P. the come to trial by approximately 20% from 300.

Most of 430 patients.

To maintain our pre specified conservative statistical power for Cam Twos primary end point.

We do expect come to to fully enrolled by the end of this quarter and remain on track to file a first new drug application for creative injection in the second half of next year.

In addition on the corporate side, we entered into a nonexclusive commercial license agreement with interest bio pharma for oral formulation rights to entrances Pip intelligence technology to develop and commercialize boil cursive, the and any indication worldwide, excluding South Korea, and Japan now.

This aligns with our strategic goals to allow advancement of oral cursive into phase three trials next year.

Pending the results from our ongoing phase two trials.

And finally with a strengthened balance sheet from a 136 million dollar follow on offering in July of this year.

We are well positioned for and we're looking forward to multiple major clinical milestones in the fourth quarter this year and into 2020.

So let's start with our lead program, which is cursive injection and hemo dialysis patients with CKD a pea.

That's a pivotal program includes four phase three studies to come Wanna, U.S. efficacy trial, which read out positive top line data in may of last year come to a global efficacy trial.

We also have a U.S. open label 52 week safety study on a global open label safety study.

Both Cam wanting come to were designed to investigate the efficacy of cursive injection or their doors of 0.5 micrograms per kilo versus placebo and that's administered three times per week after schedule dialysis sessions over a 12 week treatment period, and we also have a 52 week open label extension fees for safety.

And the topline results, we announced in May of this year for come one analysis of the primary endpoint demonstrated that cursive injection significantly reduced etch intensity with 51% of subjects achieving at least to three point improvement in worst edging intensity as measured on in America grading scale or in.

As compared to 29% of subjects in the placebo group.

The trial also met all secondary endpoints, 39% of subjects treated with Garcia the achieved at least a four point improvement and the worst pitching intensity and arrest compared to 18% and the placebo group and patients. So inclusive also experienced statistically significant and clinically meaningful improvements and it's really the quality of life.

Measures as assist with two complementary multi dimensional actually two well questionnaires the five DXJ and the skin index Pan.

Chris If I was also generally well tolerated with a safety profile consistent with prior clinical trials at best those and overall these data indicate a robust sustained onto perednik effect of cursive over a three month treatment period.

More data from the Cam one trial will be presented as a late breaking presentation at the American Society of Nephrologist annual meeting this Friday and Washington DC.

Moving onto our ongoing pivotal phase two phase three trial come too, which is a global study similar in design to come one in October of this year, we announced that we increased target enrollment for this trial to 430 patients on approximately 20% increase.

From the 350 original target and that's was based on the recommendation of the Idmc to maintain a pre specified conservative statistical power for the primary endpoint.

This additional enrollment is progressing well and we expect to complete fill enrollment, but before the end to the fourth quarter.

I'd also like to give a quick update on our ongoing long term safety studies.

Open label 52 week extension safety trial, which was initiated in Q2 2017. Currently has approximately 185 patients through six months of treatment with over 100 of these patients having completed one year of exposure.

To date, the safety and Tolerability appears to be consistent with data reported from our first phase three on prior phase two trials of cursive injection and hemo dialysis patients and based on the most recently completed the independent data safety monitoring board evaluations. The last of which was in October of this year No news.

Or inconsistent safety signals have been observed.

Our second open label 12 week Global Safety study launched in the second quarter of 2019 is expected to enroll up to 250 patients.

As a reminder, that trial was not required by any of the regulatory agencies, but rather was part of our strategy to use additional clinical sites took celebrate the safety exposure is required for a potential andy's filing.

So overall, we're pleased with the progress we've made this quarter across our com pivotal phase three program and hemo dialysis patients and with no therapies currently approved in the U.S. or Europe , we're working expeditiously to advanced or Suva injection pending post of data from come to try and Andy Andy a filing and the second half of 20.

The 20.

[noise] aligned with us timeline for regulatory filing we've also initiated key pre commercial activities across functional groups, including Med affairs commercial and C.M.C., where we've already established an appropriate CMO agreement to enable commercial scale manufacturing. So we look for.

Forward to updating you on these activities as we move closer to end the submission next year.

No I'd like to shift to the second major part of our pipeline our ongoing programs with oral cursive, which we believe could be a potential novel treatment option for patients with pruritis across multiple clinical populations.

So turning to our lead oral cursive a programmer ongoing U.S. phase two trial for pre dialysis stage three to five CKD patients with moderate to severe provide us. So that's where I was a multi center randomized double blind placebo controlled 12 week trial designed to evaluate the safety and efficacy of three doses.

Of oral cursive, a 0.25 mix 0.5, Megs and one Meg top of strength given once daily to these patients.

The primary endpoint and this trial is the change from baseline and the weekly meeting of the dam Daily 24 hour worst itch, and our escort week 12 of the treatment period and secondary endpoints include change from baseline and actually the quality of life scores at the end a week 12 as assessed by the total is going to extend and five DH skills.

As well as the proportion of patients achieving an improvement from baseline of greater than three points or greater than four points with respect to the weekly mean of the daily 24 hour West <unk> Chen or a score at week 12.

In July we announced completion of enrollment and this trial following the recommendation of the Idmc that the trial did not require any modifications to the original enrollment target of 240 patients based on an interim statistical power analysis. So we're currently completing data cleaning.

That's trial and we remain on track to report top line data a little later this quarter.

We believe there's significant opportunity for oral cursive I'm pre dialysis CKD patients were based on providers related drug prescription data. It's estimated there are approximately 2.5 million patients in the U.S. currently receiving some sort of treatment for providers and that's typically generic and he has to means recall.

Well Steve rides.

Neither of which effectively serves to alleviate the provide us related quality of life burden for these patients in the long term.

We also recently initiated phase two trials for the treatment of provide us into additional populations.

Atopic dermatitis or a D and primary biliary, calling giteau sort of PBC, respectively.

Hey, D. as of course, one of the most common chronic inflammatory diseases with prevalence rates of up to 5% in adults and approximately 25% in children providers is the defining symptom of a D with a point prevalence estimated at approximately 87% to 100%.

And then a similar fashion to CKD associated provide us current treatments across the patient spectrum fall short consisting of topical corticosteroids high goes on to has to means or antidepressants.

In July we initiated randomized double blind placebo controlled phase two study designed to evaluate the efficacy and safety of or increases in moderate to severe providers and approximately 240 patients with a topic dermatitis.

Subjects were randomized to three tablet strengths of oral preserve a 0.25, Megs 0.5 milligrams and one milligram taken twice daily versus placebo for 12 weeks, followed by a four week active extension phase.

The primary efficacy endpoint is the change from baseline and the weekly meeting of the daily 24, rich and our Esso iron ore score at week 12, with the treatment period and secondary endpoints include change from baseline actually the quality of life scores as assessed by the total index Tan and five DH scales.

As well as a proportion of patients achieving an improvement from baseline of at least four points with respect to the weekly mean of the didn't daily 24 hour I on area score at week 12.

We do expect this trial to be fully enrolled next quarter.

We expect topline data readout leader in 2020.

We also recently initiated a phase two trial in patients with provide us with hepatic impairment Judah PBC.

Provide us as a common symptom of color static liver diseases with 20% to 30% of patients experiencing provide us over the prevalence of up to 70% seven zero percent in patients with PBC.

The phase two multi center randomized double blind placebo control 16 week trial is designed to evaluate the safety and efficacy of one milligram tablet of oral cursive taken twice daily versus placebo and approximately 60 patients with PBC and moderate to severe providers.

Primary efficacy endpoint in this trial is the change from baseline the weekly meeting of the daily 24 hour worst agenda Rescore weeks 16, and secondary endpoints include change from baseline and actually the quality of life scores as assessed by the total skin index 10, and five DH skills as well as the assessment of a portion of patients achieving.

An improvement from baseline of at least three points with respect to the weekly mean of the daily 24 hour worst edge and our escort weeks 16.

We aim to report topline data from less trial.

In 2020.

So overall, we're encouraged by our progress this past quarter, our clinical team is working hard to execute on several key milestones in the coming weeks and months, which will position us for a significant events this quarter and into 2020 and in addition, our success will follow on financing has significantly.

Strengthened our balance sheet and position the company well to achieve our late stage development and regulatory goals through 2020.

And with that I'll now turn the call over to money who'll discuss our financial results for this quarter in more detail.

Thank you direct and good afternoon, everyone. As a reminder, the full financial results for the third quarter of 2019 can be found in our press release issued today after market close.

For the third quarter of 2019.

We reported a net loss of 32.8 million or 74 cents per basic and diluted share compared to a net loss of 19.4 million or 51 cents per basic and diluted share for the same quarter of 28 team.

For the third quarter of 2019, we recognized revenue of 5.8 million compared to 5.1 million for the same quarter of 2018.

For the third quarter of this year, we reported R&D expenses of 36 million versus 22.3 million in the same period of 2018.

The increase in the third quarter of 2019 was primarily due to the upfront payment of 8 million related to the license agreement that interest.

A net increase in clinical trial costs as well as increases in stock based compensation expense and payroll related costs.

Gee the expenses of 4.2 million during the third quarter of 2019 compared to 3.2 million in the same period of 2018.

The increase in 2019 was due to higher consulting and accounting fees as well as increases in stock based compensation expense.

Other income was 1.3 million for the third quarter. After any 19 versus 1 million for the same period of prior year, resulting from an increase in net interest increase in interest and accretion income due to higher average balance of our investment portfolio for the 2019 period.

As of September 30, get 2019, our cash cash equivalents and marketable securities totaled 249.1 million compared to 182.8 million at December 31st 2018.

This increase in the balance of cash and marketable securities primarily resulted from net proceeds of 136.5 million from the follow on offering of common stock in July of 2019, and proceeds of approximately 6.1 million from the exercise of stock option.

That was partially offset by cash used in operations of 78.1 million.

Now turning to our financial expectations.

Based on projected costs, the for clinical development plans and timing expectations, we expect that our current cash cash equivalents and marketable securities as of September Thirtyth 2019 will be sufficient to fund our operations into the second half of 2021, not accounting for any potential.

Milestone payments under our existing collaboration.

I'll now turn the call back over to Michel for Q any session.

Ladies and gentlemen to ask a question you will need to press star one on your telephone.

To withdraw your question press the pound key please standby, we've compiled the Q and a roster.

Our first question comes from Chris Howerton of Jefferies. Your line is open.

All right well I guess I have stayed on the phone line. Thank you money in jail.

For the background anyway, thanks for taking the questions as well I think for me.

Just a couple so for Derrick I think last time, we spoke there was some potential for a discussion with the FDA regarding accelerated approval and also potentially you know some discussion about an abbreviated safety database. So just checking into see maybe.

As you under discussion with the FDA and just any those thinking has evolved overtime.

Hey, Chris Thanks for the question I think I think what you're referring to is the idea with the with the oil cursive a program for pre dialysis patients.

There are thought as from a regulatory perspective that the exposures, we've already achieved with Ivy would be credited towards an N D for oral cursive of for the pre dialysis population. So the thought was for that particular application with oral cursive about the would be the.

Possibility and again this is.

Obviously up to the FDA per consultation, but the possibility that we could file and sndk.

In relation to that particular patient population, whereby we could reference the safety exposures, we've already achieved with IB.

That's where we think we have.

A possibility of of an abbreviated or shortened and D.A. not with our cursive an injection program, where our plan has been all along and still as.

Despite the fact, we have a breakthrough designation we take the conservative view here, we're gonna have to.

Large phase three trials in relation to the efficacy component and we're going to achieve I CH guidelines in terms of both overall exposures and long term safety exposure, so thus or lesser approach were both of those programs.

Got it okay, well, thanks, so much for that a clarification I guess in the.

For the other question I would have maybe it's just related to the chronic liver disease or just because I don't think that that's been discussed too much I'm just maybe if you could give us some thoughts in terms of what a clinical meaningful outcome would be in that patient population.

In particularly since we already seeing with the enterprise reduction would be in chronic kidney disease. So do you think that same type of magnitude is the.

Type of the effect, one would expect and clinicians would hope to see or is a different frame of reference.

That's a great question, Chris first of all let me, let me see right up front of course is no available effective therapies for the patient class as of yet so.

Anytime soon.

Yes.

And any therapy here is going to be an advancement and when it comes to clinical meaningfulness, where as you know where we're quite confident in relation to CK D.A.P., whereby we essentially empirically looked at clinical meaningfulness based on our phase two data set really at the request of the F.D.A. When we were in discussions related to breakthrough.

Uhhuh designation and there.

By virtue of the anchored statistical analysis, we know the threshold for clinical meaningful clinical meaningfulness in the CKD hemo dialysis patient patient population as approximately three points, that's something we haven't looked at them lever and so we're going to have endpoints. The accommodate both 3.4 point.

Tons and as you know four point has been the dogma a in relation to dermatological indications there hasn't been a great deal of data related to provide us an lever patients, but we're going to look at both thresholds within the patient population.

Got it okay, all right well thanks for taking my question and I'll hop back into queue. Appreciate it thanks, Chris.

Our next question comes from Jason Gerberry of Bank of America. Your line is open.

Oh, Hey, thanks for taking my questions. This is she on for Jason to from me.

Yes on the D.S.M.B. recommendation to increase become Roman size, roughly 23% for Cam through maybe if you can help us help walk us through how that's the right and where that that M. Romano expansion I thought does not.

Our next patients for treatment effect size compared to what we've seen from Cowen one and the second question is on a topic or I'm just curious.

Where do you see although of course to buffet into the pipeline, where there are about perhaps.

Biologic and oral Takeda Immunomodulators and down mid to late stage development for a topic John Thank you.

Okay. Thanks cheap so so in the first question so as the Idmc recommendations that we increase the sample size than that was based on you know.

Conditional power analysis. So there what we're trying to maintain is a very conservative level of power to see a statistical difference between the two groups from that analysis. There really has no influence as to what the odds ratio as that's point or the P value as at this point, it's really analysis based on beta and not al.

So we're trying to make sure. We if you like reduce the odds of messaging a statistical difference so there's no.

Read through if you like from having to increase the sample size to achieve that power as to the size of the effect size between the two groups. There. So that's really just a bit analysis is not an alpha analysis and not pharma and to the second question in terms of 80 or you are correct there seems.

To be a new biologic for a de every other week popping up but all of those biologics are essentially focused on the moderate to severe disease. The topic population and as you know that's the mud minority of that population with the vast majority been mild to moderate pathology and what.

No one is.

Well known in the literature, and we certainly know from enrolling in our trial is that the degree of provided us and the mild to moderate population can be very severe.

So so there we think a feel like our advantage is going to be a it's a novel option for the vast majority of a topic dermatitis patients where biologics are simply not appropriate for that population and even within the moderate to severe.

The population there may be an opportunity to use worker server in combination with a biologic for the most severe patients where they're not perhaps getting more rapid response to their providers.

There we see.

No obstacle to use in our molecule or drug candidate with any of these biologics as you remember we don't have any metabolic issues with with cursive, a it's not metabolize through the lever there is very.

Minimal opportunity for drug drug interactions here. So there's really there's really two two aspects to this strategy here would be a first line therapy on it so on.

And treating provide us moderate to severe providers really across the population than for the more severe patient it could be used in combination with with any of the biologics.

If I may.

A follow up question on banks had a collar your profile on the 80, just curious I know that you have sat.

Obviously, the phase two main criteria is gonna be focusing on the moderate to severe patients, but just curious how you're going to be able to leverage the enrollment criteria to make sure you have a healthy makes it a mild to moderate moderate to severe enough I used to thank you.

Yeah. She does that that's the magic of clinical trials, we can we can stratify within or groups to make sure. We have the desired proportion of mild to moderate patients on moderate to severe patients within those groups and that's what we're doing.

Thank you.

Thanks next.

Our next question comes from David Amsellem of Piper Jaffray. Your line is open.

Thanks, So wanted to delve a little further into the upsizing of the come to study in forgive me. If you if you addressed this.

In summary, or even tangentially, but I wanted to get your thoughts Derek on what could explain.

The calm on those not upsize, but this was upsized and.

I guess I'm kind of theorizing, because you have European sites.

In income to and and it's these are patient reported outcomes.

Measures that there might be some variability between between the two studies and I'm. Just wondering if you think that that is something that holds anyway or are there might be something else going on.

Yeah, Thanks, David and you know you've come up with.

What we regard as one of the most likely explanations, although I have to say, we don't have any empirical data as you know we don't see any data as part of this interim a conditional power assessment as all with the Idmc, but.

As as you well no.

There's a historical data out there are particularly with patient reported outcomes that they can be differences and response rates and certain regions of Europe versus versus the U.S. or assumption as because really the only main difference between the came to an account one the pretty much analogous and design.

And size is that we've included some X U.S. sites and the come to trial or assumption is that we've introduced some additional variability.

Setting where more likely to see a mall or a healthy plus he.

The ball response.

If you will.

Compared to the more severely ill.

CKD and and.

PBC patients how do you think about that.

Yeah, you know that does does a good question David that don't also have any rationality to to sway me one way or the other we just don't have enough data, yet and indeed to come up with any of that and in terms of placebo rate. Some what I can say is based on.

Study, so far which.

As you know have focused in on on CKD, We we do tend to see similar placebo rates across trials.

For those particular.

I would come from providers. So so that is one piece of data we do have as of yet I can give you data empirically across patient populations, but that's something we're going to get to next year and we'll have that data available, but you know.

We just don't have enough data to know whether the degree of response and placebo is going to be related to the degree of pathology or the duration of that pathology and the patient not sell data were interested in and of thought about but it's just data we don't have yet.

But you know.

As I've said a couple of times on these calls we think by virtue of where we act in the provided as pathway.

We really should have.

The ability to a few like benefit the poetic response by virtue of the Kappa activity not only on those sensory affluence, but also on immune cell. So there should be a dual benefit to the patient regardless of what the initiating pathology is there. So that's the theory and and you know in a couple of.

Quarters time, I guess, we're going out the data, we can discuss that and real empirical detail.

Okay and then one last question is another hypothetical to the extent that you do get a good signal any topic derm you know how does that inform your thinking regarding pruritis, we're exploring for treatment of Pruritis and other dermatologic indications.

So I'd, just say psoriasis or even smaller populations like for going out alaris.

How do you think about that.

Okay.

Yeah, I can't I think they have a mechanism that that they should be broadly applicable by virtue of how we work and our ultimately it and I know you and I have discussed as a couple of times I think our ultimate aim for CRE server.

And Korean providers for oral Chris server is the if our theory is true and were broadly applicable then at some point, we should have a broad label.

For the molecule, we should be somewhat analogous to the old approach for chronic pain medications. So our belief as it was if we should can show efficacy if across these major you know perednik part. So you know systemic disease related provide us.

Dermatological related Pruritis neuropathic really they provide US then we could make a strong case that this is a molecule. They should have a broader label on them. We can see application really across the spectrum upward peretti conditions. So that's the approach we're taking broadly at that point, but obviously we folk.

Just on patient populations, where we think.

We have the most promise unseen or response and CKD was an obvious place to start there was a great deal of if you like EM.

Validating information related to the mechanism and then there's also some interesting data related to atopic dermatitis and Kappa that makes us think that could be an interesting patient population also but ultimately I think if the mechanism as broadly applicable we'd like to see the us with a with a broad label.

Okay, great. Thanks Darren.

Thanks, David.

Our next question comes from Annabel Samimy of Stifel. Your line is open.

Hi, Thanks for taking my question I don't know if you answered this earlier, but have you had that after the meeting enough and I.

I know you have a breakthrough designation did you mention that youre able to gain fast track.

I'm kind of fast track status from them or are we talking here about that.

Yeah now when we were not we're not lined up for fast track status in relation to the CRE Suva injection program, that's not something we're counting on.

And I was saying earlier Annabel were really taken the conservative view that we need.

To follow I see age guidelines here and we designed the program that way to make sure that when we filed US a very robust package that goes to the agency with all the appropriate you know requirements in terms of overall exposures and long term exposures within it so we're not counting on fast track exposure.

Where we would see a benefit with breakthrough and something we're certainly going to apply for would be probably auditory priority review once we filed the N D and that's certainly something we're going to be looking for by the that's point, we're not we're not counting on fast track status.

Okay.

Actually.

Thanks for clarifying that.

Okay, Secondly, I know the right.

I mentioned that with the new powering of comp to you're not <unk> <unk>, it's really not alpha to beta that that you're really aiming for.

I mean, maybe I can ask a little bit differently.

To what level do you think delta can drop it still reached statistical significance for column to.

Maybe.

I just think about it that way.

Why don't I don't know if I didn't have an answer to that I'm not qualified statistic way to give you that answer Annabel, let me just say that we powered.

Both trials.

Similarly based on our phase two effect sizes are odds ratio. So they're both powered if you like with the same assumptions within it and obviously.

Our assumptions in relation to standard deviation were based on our U.S. phase two and we did apply that both to our U.S. CAD, one and our global come too. So there might be some differences there that you know weren't accommodated and those assumptions, but the actual.

Perfect size or or odds ratio, we've modeled the on we didnt, we didnt change between the.

The two trials and again, we said the upper threshold at a conservative level, it's not really related to.

You know.

Again, a statistical difference here, we're increasing the likelihood that we can see a difference and from that I really can't derive an alpha value I'm sure. There's some smart statisticians who could.

Based on some of the data, but they oversight dinner I into Idmc. So we don't see any of that data and so so this is really a means to reduce the odds of a have a mess if you like.

Alright, and then.

Just on the last question I have is related to.

The commercial.

Understood.

Yes are there any other activities that are going on in the background on their side are there any future milestones.

Expecting.

Some of the clinical data read outs that we should be looking forward to and just correct me.

Please I can't remember if they had any opt in rights for.

For all four CKD population can you just clarify that for us.

Yeah, right, so and over the last point just to be clear they have no opt in rights for the oral for anything that was hemo dialysis patients. So that license is solely based on CRE server injection, so that formulation, specifically for hemo dialysis patients with them with CKD, Pete So theres no opt in rights there and entered.

As of activities between the two companies.

You know, we we did have ongoing discussion in relation to that particularly as to how we're going to deal logistically with the co promotion here on the U.S., whereas you know we got we have a 50 50 split in terms of Fresenius clinics in the U.S.. So that's an ongoing discussion milestones related to development regulatory.

And as we said before so regulatory milestones, yes, when we get to that point and then of course commercial sales milestones in the license territory, which is which is X U.S. Your predominantly some other territories and then sales to your buy assets or sales royalties tiered by sales amounts of fuel.

Like and and the license territory. So that's.

That relationship was was drafted.

The next.

That doesn't milestones is around 30 million appetite to the regulatory outcomes yeah.

Is it out camera filing.

It's an outcome so nice okay.

Okay, Alright, great. Thank you.

Our next question comes from Charles Duncan of Cantor Fitzgerald. Your line is open.

Hi, This is our piece the problem for Charles.

One question after oral of course as well.

Yes.

We dialysis study.

You have varying degrees of kidney function, which could affect elimination of the drug.

Dissipate varying degrees of kidney function make somehow compound.

Results on both from a safety and efficacy points.

No. He does a great question. It was actually one of the reasons that before we started the phase two we actually ran a PK study a phase one study specifically within these pre dialysis stage three to five patients and there you are correct. There was some degree of variability in kidney function, there, but not enough.

To to change our dosing regimen for all of those patients from once a day, it's really a question of the land for the beta phase on the elimination of a four or five and you're correct those almost totally via the kidney, but we did per PK analysis, we really can cover all of those patient types with once a day.

Dosing with the with oral care server.

Okay. Thank you Andrew Thanks, Pete I was wondering you originally you announced an oral presentation that kidney week 29 feet.

Yes.

Do we should we anticipate seeing there.

You are going to see a little more detailed come one data.

And that will be presented by one of the Cam one p. eyes Dr. Stephen fish ban on Friday afternoon ideas then.

Alright, Thank you congrats on core.

Thanks Pete.

Our next question comes from Alan Carr Needham and company.

Your line is open.

Hi, This is Joey on for Alan Thanks for taking my questions.

So for the oral.

Of course to phase two.

What effect size on its interests are you or do you expect to see.

Based on some of the PK.

Earlier PK work that you've done just in terms of.

Number of patients with greater than three point improvement in more stage and arrests would you sort of expected to be similar to what.

It was observed and calm one.

The 50%.

Yeah, Thanks, Jody I mean it.

I won't have the I don't have the answer that today, but we will have the answer to that very very soon in terms of the absolute number there, but again, our assumptions on design and the oral.

Phase two trial were really based on data we had from our Ivy experienced within CKD patients. So if you like the effect size. We've modeled that on is related to the IB effects as you're correct not assumption and you know the other.

Comforting aspect to the phase two data set of course as you know we completed our interim conditional power assessment in July of this year, specifically within the phase two trial and there we didnt increase the sample size to maintain our are conservative power to see a difference between the group so that makes us feel.

Good that we are assumptions based on I view, the oral were actually.

Viable inappropriate and we were in the ballpark of.

Hi power high beta to see a statistical difference.

Great. Thanks, and just as a follow up would you be disclosing scanned X 10, and no five D H data in the topline as well.

Yes, we will that we will who will certainly have the the main primary obviously and the main secondary endpoints.

Great. Thank you.

Thanks Julie.

Our next question comes from Aster Hong of Janney. Your line is open.

Hi, I first question, so as we get closer data from the phase two trial about where of course super and non dialysis patients I'm, assuming that it's positive and initiation is set to kick off next year a phase three if it is positive what what a phase three trial design look like.

Thanks, Aster and that's really going to be based on what we see in our phase two data and as you know that's that's phase two is really a dose ranging trial.

You know we have our ideas based on exposure as to which tablet strengths should be appropriate, but we really need the empirical data to see what's the most appropriate.

Tablet strength to carry forward into into phase three so that's the first question, we need answered from our phase two.

We're obviously looking for sustainability of effect and that's why we run. This phase two is a if you kinda like a phase three like 12 week treatment period. So we are going to get valuable data there that's going to establish sustained effect, which which is important for us and based on that these these types of data I puts and also.

So actually the effect size, we see within that trial that will dictate the tiring requirements, we need and therefore, the sample size to run the phase three so we really need to the phase two data, which is not too far away now I'm before we think about what the design of the phase III looks like but in terms of treatment period is.

Going to be analogous to what we've just run interface to by design.

And then what can we expect at the World Congress of pitch meeting next month.

Have you just you can expect to see some really nice data from from US is going to see.

Yes, they do Ivy study, you're going to see some analysis on sleep responses from our from our eight weeks phase two study and hemo dialysis patients you're gonna see some more quality of life or data presented there also and post or form a unless I just discussed with them.

Joy and Pete well the Cam one dataset is gonna be on oral late breaker and you're going to see a little more detail from or Cam one phase three trial.

Okay, great. Thank you.

Thanks after.

Our next question is a follow up from Chris How're kind of Jefferies. Your line is open.

Hey, Thanks for taking the falling just really quick I just wanted to follow up on the entered those question with respect to the meeting in the fall with the FDA, which was then do do we have that wrong that there was going to be a meeting.

And if not you know ER or if there was the meeting have you had that you had in what were you know what we are you hoping to get alignment there just maybe a clarification for that or or set of straight I suppose.

Yeah, Chris Dodd I'm not sure what.

Meeting in the fall, you're referring to with respect to change in the status of the application and trying to go for.

Accelerated or or you know some sort of.

Advanced filing mechanism, that's not something only happened and we did have communications with the F.D. on the logistics of how we're going to file our data and the various modules and those are those are going along fine and we have all the answer is we need there in terms of moving forward, but there wasn't a specific meeting related to understand.

You know accelerated approval.

Okay, Great I'm totally makes sense I guess made it up then I appreciate the clarification. Thanks, Hi, Chris Thank you.

There are no further questions like to turn the call back over for any closing remarks.

Okay. So thank you everybody for joining us today I'd like to thank the Cabot team our study investigators and most importantly, the patients who participate in our trials for their continued commitment and support and we look forward to updating everybody again very soon thank you everybody have a good day.

Thank you ladies and gentlemen. This concludes today's call. Thank you again for your participation you may now disconnect.

Have a great day.