Q2 2021 Cara Therapeutics Inc Earnings Call

August 9, 2021

Second quarter 2021 financial results conference call.

All participants are now in a listen only mode.

And there will be a question and answer session at the and please be advised that this call is being recorded at Cara <unk> request.

I would now like to turn the call over to the car T. Please proceed.

Good afternoon. This is cole hurts Ferguson with Stern Investor Relations and welcome to Cara Therapeutics second quarter, 2021, and financial results and update conference call. The news release became available just after 4 P. M. Today and can be found on our website at Ww Duck Cara Therapeutics Dot Com 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 1095. 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 Companys product candidates, including the company's projected timeline for FDA review and potential approval and commercial launch of course, Suva injection for dialysis dependent and CK D Dash AP the expected timeline for conducting meetings with.

The FDA concerning the Companys product candidates, including oral course, duva and D. D CK, Ddos, AP and AR AP and the potential for the Companys product candidates to be alternatives and the therapeutic areas investigated the potential impact of COVID-19 on the company's clinical development and regulatory timelines and plans and the company is.

Good cash reach 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 factors sections of the company's most recent annual report on form 10-K, and its other documents subsea.

And we filed or furnished to the Securities and Exchange Commission all forward looking statements. All forward looking statements made on today's call speak only as of the date 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 date on which they are made practice.

Participating on today's call are Dr. Derek Chalmers, Cara, President and CEO and Mr. Thomas Riley Caris, Chief Financial Officer, I will now turn the call over to Dr. Chalmers.

Okay. Thank you Paul and good afternoon, everybody and thanks for joining us today on the call.

We have continued to make significant progress across our pursuit of a development pipeline and the second quarter of this year.

With our NDA for our lead product candidate <unk> injection for the treatment of moderate to severe pruritus in hemodialysis patients under priority review.

And our interactions with the FDA have progressed efficiently.

And on schedule and through the completion of our late cycle review, we remain on track for and expect to produce a target action date.

August 23rd of this year.

In addition.

We continue to make important progress across our oral cursive pipeline programs to.

To that and and Q2. This year, we reported topline results from our phase III care dose ranging clinical trial of oral <unk> for the treatment of moderate to severe pruritus and atopic dermatitis patients.

Based on pre specified analysis of that data set we've identified the appropriate patient population and dose strength to move forward.

And pending the outcome of discussions with the FDA later, this quarter and to initiate a phase III registration program and mild to moderate atopic dermatitis patients by year end.

We also plan to meet with the agency and the coming months to discuss the appropriate pre dialysis <unk> patient population to move forward to phase III and that program.

And we continue to enroll patients and our ongoing trials and both PVC and Natalia <unk> with the aim of establishing and pursue as efficacy across a range of patient pathologies.

And what treatment of chronic pruritus remains a significant unmet need.

So the remainder of 2021 is shaping up to be truly transformative for the company with the potential approval and commercial launch of the first the first therapy for the treatment of pruritus in hemodialysis patients and potential advancement of oral crisp into registry.

<unk> trials.

So what that and let me provide you with some additional details across our main pipeline programs.

Beginning with our most advanced program <unk> injection.

Following the Fda's acceptance of our NDA filing with priority review and the first quarter of this year, our dialogue with the agency has progressed well and without any review of delays.

Based on the outcome of our late cycle review last quarter. We currently do not anticipate and in manufacturing and inspection delays and we expect the agency to meet their particular target action date of August 23 of this year.

With that in mind, we remained focused along with our U S commercialization partner <unk> pharma for the commercial launch of <unk> injection and the second half of this year.

As a reminder, based on V Force established U S. Neurology sales force and there are deep rooted relationships with both large and small U S dialysis organizations Cara.

We executed a strategic license agreement with <unk> pharma and the fourth quarter of last year for the commercialization of <unk> injection and U S dialysis clinics under our Cara, 60% <unk>, 40% profit share arrangement.

And we firmly believe this will support increased launch momentum and adoption of <unk> and the U S market if approved.

The financial considerations of the VFR agreement contributed significantly to the current strength of our balance sheet.

Based on the terms of the license the company will be eligible to receive an additional $50 million common stock investment upon U S regulatory approval of.

<unk> injection.

And post launch.

Eligible to receive payments of up to $240 million and U S sales base commercial milestones.

On <unk> on injection reimbursement activity.

Ongoing interactions with CMS have been productive and we plan to file both our to dapper on.

And heck picks applications later in Q3 again, assuming pursue that injection approval.

Turning to ex U S. Commercialization planning we were also very pleased to announce earlier this year that the European Medicines agency accepted the MAA for <unk> injection for the treatment of pruritus associated with chronic kidney disease and hemodialysis patients.

The EMEA will review the application under the centralized marketing authorization procedure.

And under our 2018 license agreement with <unk> Fresenius will be responsible for the commercialization of <unk> injection across European territories with Cara eligible to receive tiered double digit royalty payments based on annual net sales and up to $440 million and tiered commercial milestones.

All of which are sales related.

The <unk> is expected to render their decision and the second quarter of 2022.

Turning now to progress on our oral Christova pipeline.

We recently announced topline results from the key or a phase II dose ranging trial of oral <unk> for the treatment of moderate and severe pruritus and atopic dermatitis patients.

First trial, you will recall was a randomized double blind placebo controlled study designed to evaluate the efficacy and safety of oral <unk> and 401 adult subjects with atopic dermatitis.

Patients were stratified across treatment groups by disease severity with 64% approximately of patients characterized by mild to moderate atopic dermatitis and approximately 36% of patients characterized by moderate to severe atopic dermatitis <unk>.

Patients were randomized to 3 tablet strengths of oral pursue over 255, and 1 milligram tick and PID versus placebo for 12 weeks, followed by 4 weeks of active expansion.

And as pre specified analysis of <unk>.

Tests really significant change and the primary efficacy endpoint was observed and the mild to moderate that as BSA less and 10% patient population.

Which was evident at week, 1 and sustained through the treatment period.

In addition, a statistically significant improvement was also observed and the registration endpoint, a 4 point responder analysis and the mild to moderate patient population with 32% of <unk> patients achieving a greater than 4 point reduction and our asset week 12 versus 19% and the placebo group.

So these care results have provided key information related to the defined patient group that is mild to moderate and active dose range.

And in effect size on the registration and 4 point percent responder endpoint from which to design appropriately powered phase III trials. So with this data in hand, and pending the outcome of our scheduled and the phase II meeting with the FDA.

We aim to initiate our first oral cursive, a phase III program and mild to moderate atopic dermatitis patients.

By year end 2021.

We also plan to present additional data on additional analysis from the care trial at upcoming medical meetings later this year.

So to step back and think a little and in terms of ultimate potential positioning of oral <unk> and the atopic dermatitis treatment landscape.

And it's clear that while provide us is recognized as the definitive and indeed, the most burdensome symptom of atopic dermatitis therapy.

<unk> therapeutic development to date and this area has focused on pro inflammatory pathways.

Rather than perretta janick pathways.

And there is a particular treatment GAAP amongst mild to moderate atopic dermatitis patients, which is approximately 80% of the day population.

With topical therapies do not adequately address chronic pruritus and systemic immuno modular tree agents are not available.

So based on its observed profile from our care dataset, we believe that oral <unk> may provide clinical benefit for these patients and provide a systemic antipruritic therapeutic option, where non presently exists.

So moving on to our program and pre dialysis <unk> patients with moderate and severe pruritus.

We recently conducted and end of phase 2 meeting with the FDA with the goal of defining a phase III program and pre dialysis <unk> patients, which would allow us to leverage the substantial clinical efficacy and safety dataset, we've compiled with pursuing and injection and hemodialysis patients.

The FDA has indicated the viability of stage 5 pre dialysis <unk> patients as a population for our phase III program and also indicated the potential to use the data from our previous trials of <unk> injection and dialysis patients to support and approval based on a single phase III clinical trial.

We are currently gathering more data related to pruritus incidents and severity and pre dialysis <unk> patients and aim to meet with the agency and the fourth quarter of this year to further define a viable patient population for inclusion and a phase III.

Program.

Finally to our ongoing phase III trials and primary biliary cholangitis and <unk>.

Before I get to that I'd like to remind everyone that due to the ongoing COVID-19 pandemic.

And in accordance with the Fda's updated guidance for conducting clinical trials.

We've implemented numerous clinical and operational measures to prioritize the health and most importantly, the safety of patients our employees and study investigators and minimize potential disruptions to our ongoing clinical studies.

Pruritus is a common symptom of call a static liver diseases, 20% to 30% of these patients overall experienced pruritus with that number rising to approximately 70% of patients with primary biliary cholangitis.

Our 16 week Phase II trial is designed to assess the safety and efficacy of a 1 milligram tablet strength tomorrow, Chris Suva taken twice daily.

Versus placebo and PBC patients with moderate to severe pruritus.

The primary endpoint is the change from baseline and the weekly mean of the daily 24 hour worst itch <unk> score at week 16.

We now expect to report topline data from this study and the first half of 2022 due to delays and site initiations and patient enrollment, resulting from the ongoing COVID-19 pandemic.

Finally, with the goal of further establishing the broad antipruritic applicability of <unk> across patient populations with underlying pathologies.

Earlier this year, we initiated a phase II proof of concept trial royalty receiver for the treatment of moderate to severe pruritus in patients suffering from Natalia <unk> and neuropathic disorder cash.

Erika rise by chronic pruritus and the upper middle and back.

The phase II multi center randomized double blind placebo controlled 8 week study is designed to evaluate the efficacy and safety of oral <unk> and approximately 120 subjects with Natasha prosthetic are randomized to receive oral pursue with <unk> twice daily versus placebo for 8 weeks.

<unk> followed by a 4 week active extension period.

Primary efficacy endpoint and has it changed from baseline in the weekly mean of the daily 24 hour washed itch <unk> score at week 8 of the treatment period.

And I am pleased to note today that this trial has now passed 50% enrollment Mark and based on our current recruitment rates, we expect full enrollment and less trial by the end of this year.

So overall our progress through Q2 in recent months has led defense laid the foundation for a very significant second half of 'twenty 1.

We very much look forward to the expected per day for target action date later this month.

For <unk> injection as potentially the first FDA approved therapeutics for the treatment of pruritus in hemodialysis patients.

And we are well prepared along with our partner <unk> pharma for a commercial launch of <unk> injection and the second half of this year.

With a strong balance sheet, we are well positioned to support our goal of initiating our first phase III program with oral pursue over and mild to moderate patients by year end.

As well as continued to progress our ongoing oral programs and CK D and PVC and Natasha Pyrostat acute patients and.

And we will be updating you on all of the progress across these programs and the coming weeks and months.

So with that I'll now turn it over to Tom to detail the financial results for this quarter.

Thank you Derek.

As a reminder, the full financial results for the second quarter 2021 can be found in our press release issued today after the market closed.

Cash cash equivalents and marketable securities as of June 32021.

Total $207.4 million compared to $251.5 million at December 31, 2020.

The decrease and the balance primarily resulted from cash used in operating activities of $44.7 million.

We offset by proceeds of $1 million from the exercise of stock options.

For the second quarter 2021, net loss was $30.7 million or <unk> 61 per basic and diluted share compared to a net loss of $25.1 million or <unk> 54 per basic and diluted share for the same period in 2020.

There was no revenue for the 3 months ended June 32021. This.

And this compared to $5.6 million during the same period of 2020.

The company recognized $5.1 million of license and milestone revenue during the second quarter of 2020.

$4.5 million of which related to our license agreement with VF.

Fee, and CRP, and 0.6 million of which related to achievement of the development milestone.

Related to our license agreement with CK day pharmaceutical pharmaceutical Corp.

The company also recognized zero point $5 million of clinical compound revenue and the second quarter of 2020.

<unk> pharmaceutical company and the FM and CRP.

Research and development expenses were $25.2 million for the 3 months ended June 32021.

Compared to $26.1 million and the same period of 2020.

The lower R&D expenses in 2021 were principally due to a net decrease and costs associated with clinical trials.

And stock compensation expense.

Partially offset by a $10 million milestone earned by interest from Biopharma. During the 3 months ended June 32021.

General and administrative expenses were $5.7 million for the 3 months ended June 32021.

This compared to $5.4 million and.

And the same period of 2020.

The higher G&A expenses in 2021.

Principally due to an increase and payroll costs.

Marshall costs and legal fees.

Partially offset by decrease and stock compensation expense.

Other income net was <unk> 1 for the 3 months ended June 32021.

Compared to <unk> 6 million and the same period of 2020.

The decrease and other income net was primarily due to a decrease in interest income, resulting from a lower yield on the company's portfolio of investments and the 2021 period.

Now turning to our finance guidance.

Based on timing expectations and projected costs for current clinical development plans.

Cara expects that its existing on restricted cash and cash equivalents and available for sale marketable securities.

As of June 32021 will.

And will be sufficient to fund our currently anticipated operating expenses and capital expenditures into 2023.

Without giving effect to any potential milestone payments.

Or potential product revenue under existing collaborations.

I will now turn the call back over to the operator for Q&A.

Thank you at this time I would like to inform everyone in order to ask a question. Please press star 1 on your telephone keypad again that is star 1 to ask a question.

We have your first question from Jessica Fye with Jpmorgan Your line's open.

Thank you for taking the questions.

Firstly can you talk about the timing for the recently announced API supplier and maintenance.

Is this debt.

And closer to <unk>.

And Youll see.

And does it affect the Anda and NDA.

Yes, hi, thanks. Thanks for the question now is the standard.

Commercial API supply agreement does not affect the Paducah date on <unk>.

Review of the NDA and any way whatsoever.

Okay.

And kind of order program in non dialysis setting.

And do you expect to initiate and <unk> build on.

Will you wait for they are geared usage and putting things up earlier stage patients and the tri.

Start irrespective of day.

No. So presently we're gathering.

Both patient data and we have physician research underway.

In relation to incidents and severity of severity of providers.

In pre dialysis.

CK D patients.

And once we've gathered that information Philly.

Our plan is to engage with the FDA probably in Q4 of this year.

To get and agreement on a viable pre.

Dialysis <unk> population for inclusion and that phase III program. So it's likely that that would initiate.

Early in 2022.

Got it thank you.

Thank you very much.

We have your next question from Chris Howerton with Jefferies. Your line is open.

Great Congratulations very exciting times for Karen and thanks for taking my questions.

Again, thank you Ronnie.

And of course, so for the I guess what are the maybe following up on the.

Added criteria for the oral CK day program was in the sense that the FDA did not feel like there was unmet need and in less severe patients and stage 5 or was it.

The case, where there was insufficient information and make that kind of a judgment call. I guess is 1 question and then the second question I had Derek was.

Related to the atopic dermatitis program I think I feel like you described this last time, but if you could just remind us what it is that you'd like to align with the FDA with respect to that program is there something.

In addition to what you've described to US here in terms of going after the mild to moderate and the dose range that you believed to be active.

Right. Thanks, Chris.

Let's start with your <unk>.

<unk> question and I feel as the latter of your 2 options in relation to the FDA there just.

There is a lack of information presently in relation to pruritus and incidence and severity of that and earlier stage <unk> patients relatively speaking towards.

In relation to stage 5 which is obviously the final stage prior to hemodialysis. So.

With that in mind, our view has been and we are on.

I am perfectly develop and that information.

And collaboration with the National Kidney Foundation will run and patient research we're on.

Also run and physician research and we aim to get if you like.

And more recently are more up to date and information we can use there to define the breath of the pruritus issue and.

And the pre dialysis <unk> population that we can then uses.

Basis for a discussion with the FDA and relation to to where we define that population for inclusion in the phase III. So it's really a <unk>.

Filling the gap in terms of lack of available information if you like real time, and those and those earlier populations that we have underway.

So that's that's the progress there and as I said, we aim to have that meeting with the FDA and the coming months to define that.

In terms of the in terms of a day.

And I'm not quite sure what you're getting out there our view on the day program is we're looking for we're looking for a label.

To treat moderate to severe pruritus, specifically within mild to moderate a day patients that are in need of <unk>.

Systemic antipruritic.

Therapy.

And and our view there is that based on our phase II data, we certainly see and appropriate profile profile from monotherapy.

That we can significantly reduce pruritus.

Rapid onset.

Have a very attractive safety profile for the drug.

And so so that's the basis of our.

And the phase 2 briefing book and I would like to see that program progress.

The agents got it.

Okay. So it's simply got it okay alignment on trial design and the final regulatory exactly exactly.

<unk>.

And so we're always.

I always crystal clear.

And I guess, maybe if you wouldn't mind just a quick follow up to maybe my previous question is there do you.

And what have you disclosed about your view of the epidemiology of the stage 5 patients that would experience moderate to severe pruritus.

Well.

Just on the data and said there is some published did add though you could find interest there is.

Adopts analysis to adopt surveys looking at severity and frequency and pretax free hemodialysis CK D patients and it's certainly clear that the severity of the pruritus increases with the severity of <unk> disease.

No.

What we are looking at and beginning to CNR analysis is.

Somewhat similar frequency and stage 4 and stage 5, particularly later stage 4.

And and.

As you know.

The dividing lines between those are somewhat arbitrary it seems clear that <unk>.

Physicians really.

Regardless, we got the patient in terms of late stage versus earlier around these defined thresholds vs Egfr definitions and.

And from their analysis and their feedback is clear that day regard pruritus is a significant issue and late stage pre dialysis <unk> patients. So we're just trying to put some parameters.

<unk> around that population so we can define that.

More accurately and then and then talk to the agency again.

And what should be included.

Okay No that's.

Very clear I appreciate the added color, okay, well, thanks, I appreciate and congratulation and answer the questions.

We have your next question from David and to limb with Piper Sandler Your line is open.

And thanks, just a few so first on the.

I apologize if I missed this but is the FDA onboard with the definition of mild to moderate per the body surface area of being under 10% I mean is that something where there could be potential for daylight between.

Between you and the agency just just give me a refresher.

On that in terms of the mild to moderate definition. That's number 1 number 2 is and liver disease.

I guess the question here broadly is to the extent that you do show a signal in phase II, how wide of a population with your SaaS and our phase III.

Program.

Would it be primary biliary cholangitis or.

Something more broadly and patients with hepatic impairment.

And then thirdly, and Thats held true prosthetic.

Seneca.

On.

Just I guess.

And maybe getting a day my excuse here, but to the extent that you have a signal and that study.

What does a phase III program look like do you have to run 2 identical phase III studies.

And Thats new indications so maybe just help us understand how you would think about that to the extent you move forward. Thanks, yes.

Yes, Thanks, David.

3.4 for you as well it was well play and so on a day yet the definition amount tomorrow, PSA less and 10% is pretty much standard.

On that they may add some iga criteria to that but that's a that's a standard.

Definition.

And for mild to moderate disease based on the extent of lesions and those patients that don't.

Thanks.

Contentious based on what we see on other labels out there and as you know.

It's a standard regulatory path labelled specific for mild to moderate patients thats not and if a new.

For the for the agency.

So that's that 1 on liver disease.

PVC and and I think we've had this discussion before.

Generally the reason you're entirely correct pruritus is.

Broadly and issue across Colas.

<unk> static liver diseases, and a number of other.

Liver related disorders and.

The reason we went for PVC initially as the incidents there.

And the severity is certainly higher than in other liver diseases.

And close to 70% there.

So that debt that.

And that we regard it as.

An important parameter for enrolling patients that we wanted consistency and their pruritus. We've left the game long enough and a superior patient reported outcome and 1 of the issues and control and placebo rates here is not to other and consistency and.

And Europe Pruritus response, so so that was the reason to use PVC as of course, and orphan indication and that somewhat.

It is a little bit and that it's much more difficult to recruit and there are certain centers, we'd like to get in there which have been difficult to get to.

Because of the Covid restrictions.

And that's a pity, but I think if we can push on here, we're going to see on uptake and.

And are patients that are soon and of course, we have high confidence and the mechanism for.

Capa and that particular disease situations since we already knew that now fewer fee and got that label extension and Japan Youll recall after their initial label for hemodialysis associated price. So we have.

Conviction that this is a mechanism that should be effective here ultimately run and a phase III program and PVC is unlikely for us I think if we move into phase III program.

And that will be a strategic decision when we get there in terms of.

And what we're seeing and these other.

And patient populations is likely to be a broader liver disease population. So that we can actually run that program and and inappropriate timeline.

So that's the view on liver disease, where really use and PVC is.

<unk>, if you like as the efficacy and the liver disease situation and it somewhat similar from.

Natasha Parenthetic and.

We think this is a it's.

As an interest and an indication per se with with probably dependent on which estimates you want to believe run were probably around 1 million patients.

And the you asked very common post to age 65, and and really nothing available again.

For those patients and I can.

Can tell you the entry.

Scores, we're seeing and these patients coming into that trial.

And are on the severe and of moderate to severe. So this is a significant cash.

Cynical issue for those patients again.

And that is a kind of a proof of concept patient group to cover the neuropathic etch area. It's a large.

There's a large patient population estimated at some 8% of all the chronic pruritus and the U S. So we wanted to make sure again and we have a mechanism that's going to be applicable for a few like a nerve related.

Disorder that induces pruritus, so so thats, where used and as our model population.

Again, we're again, we'll look at the ultimate data and decide whether we push forward here and to phase III is actually been surprisingly rapid enrollment here, which probably speaks to the size of the patient population and again, if we look at that at the end of the day and that makes sense in terms of timeline to a label.

And that might be something that might be something we'd consider it but at this point.

And we are interested in getting our first phase III and it looks like it's going to be and atopic dermatitis, and then making sure confirming efficacy.

From all these other patient populations and then we will decide which of those makes sense to push forward into larger trials. Once we have all that data.

Does that answer your question David.

Okay.

That has started locking yourself.

No no no I'm here I'm, sorry, I'm, sorry, I was on mute, but yes, no that was very helpful.

Okay.

David Thanks for your questions.

Again, if you would like to ask a question. Please press star 1 on your telephone keypad again that is star 1 to ask a question.

We have your next question from Jason <unk> with Bank of America. Your line is open.

Hey, guys. Thanks for taking my questions.

I guess first question Derek how do you envision and the ramp of a drug like IV <unk>.

And the first <unk>.

6 months to a year and.

And the dialysis setting sort of curious as you've looked at other products and the setting like ours. The bib just sort of curious if you see a faster ramp of more cautious early flow Trialing, and then sort of a buildup.

After the first 12 months.

And I'm curious and I guess locations or how the bundle could ultimately reset depending upon utilization and cost.

And then my other question and there is there is some free off city and the investment community about the potential impact of Hey, guys.

Super responders and the calm trials and Luo.

Alex I'll comment on other unfavorable FDA outcomes and that.

Space. So just curious if you can.

Address that and your comfort level around those dynamics.

Thanks, Jason.

Thanks for dialing in so in terms of in terms of ramp and <unk> and Jason and I think we've had desk and a general discussion before but it.

It is an unusual market highly consolidated and the U S. As you know.

With the vast majority of hemodialysis patients covered by 2 dialysis organizations.

1 of which we are aligned with and our and our corporate alliances and that is <unk>. The other being davita to some 80% of U S trials are concentrated within those 2 dialysis organizations and clearly.

Utility of the drug there and protocol adoption of the drug there is.

As highly important to success ultimately, which is 1 of the reasons we.

We decided to sell on our initial agreement with <unk> Fresenius and as you know and recall from that part of that agreement as we have a 50.50 <unk>.

Profit split within Fresenius clinics, so and Youre correct looking at other drugs that have launched recently and that space parse a bev of course being the only example of a drop through to dapper here. There is a rapid adoption there and we do see significant uptake and the first and the first year and.

And certainly 2 years and as you know that's important for any drug and that space is thats, where we want to assess utility for future reimbursement.

Post the dapper. So so looking at if you like V Force track record here.

With drugs, such as from our surf and not space and they are.

<unk> had great success with with rapid uptake and I do think the uptake curve and that particular market space is going to look different than a standard PCP space, we do anticipate a faster and faster ramp.

And with the pursuit of and Jake.

And but good question, yet unusual market dynamics there.

And.

And then in terms of the.

In terms of the dataset, we've used and our and our NDA for efficacy confirmation and now we're very comfortable with and certainly based on the interactions we've had with the FDA.

Through and our late cycle meeting I don't think we're going to have any issues in relation to the dataset. We've used third from both <unk> and <unk>.

That said mentioned.

Okay. Thank you.

Thanks, Jason.

We have your next question from GAAP net of bad.

And <unk> with Stifel. Your line is open.

Hi, This is Jack I am calling in for Annabel and Muni. Thank you for taking our question.

So a few things related to the do per day for IV course universe at this month.

What types of commercial activities are your partners pursuing at this time to prep for launch.

And in what priority will be for BP positioning myth and their portfolio.

And what work has been done ahead of time.

Dupont to file for the Apple payment from BMS is that something that can be done ahead of the approval or not.

And additionally.

Just for some clarification with the phase 3 trial.

What kind of options do you expect to propose to the FDA as far as design adjustment.

Side of Justice tailoring to the mild and moderate population do you feel like there are other modifications you can make to improve the statistic.

Great Jack.

Thanks for the questions thanks for dialing in and so.

Let me I think I got all of those but let me start with the <unk>. So I think as I said on the call we still expect per dose.

August 23rd in terms of preparing for commercialization and as I said on the call we will be assuming approval.

On August 23rd we'll actually be filing both are to dapper on.

And <unk> applications the following month.

So all of that is and preparation of approval and will be underway that months.

In terms of other <unk>.

Commercial prep.

<unk>, 4 and and combination with <unk> 4.

There'll be launching.

Disease state awareness.

This quarter and actually into Q4 ahead of reimbursement.

We are constantly talking with CMS and terms of reimbursement post to DARPA and that's been very productive and we will continue and <unk>.

<unk> is working with large dialysis organizations of course some of them they are very intimately.

And related to and mid sized dialysis organizations on optimizing.

Formulary and protocol placement.

Once we get pursue and injection approval.

You will see launch activities at the upcoming ASN and.

Youll meeting in November related to pursue and injection and I certainly know that <unk> 4 has rep training well underway and are planning for a launch meeting and.

In January of 2022, so all of that has been ongoing and of course prior to that we had disease education directed from both the Cara MSL team and the V..4 MSL team. So all of that has been underway and continues to be underway and preparation for commercial launch and then.

I think that covers your questions on on pursuit of injection jackpot.

Correct me, if I'm wrong and then your last question was.

And phase III.

Trial design, and how we see positioning on that within the patient population and our view there and again, it's based on empirical data and as I've said and our.

And on a pre prepared remarks, we had non lessors and heterogeneous population when we initiate that phase II phase III trial.

We pre specified where we're going to look at efficacy both in mild to moderate patients, which obviously have a different.

Pathological presentation and actually different systemic immune profile, then moderate to severe patients and it's clear.

And that we have a drug that shows.

Greatest efficacy and the mild to moderate population, so and we will also be presenting more data from that study a little later this year, which I think will help you and thinking about the Jack in terms of other endpoints, both quality of life and pathology and points that will be presented there.

But we think we are very confident on where we think this drug works works best.

And that said and the mild to moderate.

Patient population, which as you know is that defined.

Patient population for for for labeling.

The FDA. So so that's the possession and we're going to propose when we meet with the agency.

Great. Thank you so much that's very helpful.

Thank you Jack.

Okay, and if you would like to ask a question. Please press star 1 on your telephone keypad again. This is par wanted to ask a question.

We have your next question from <unk> <unk> net with a cheap HFC.

HFC Wainwright your line is open.

Hi, I have a couple of questions around the oral <unk> pre dialysis program can you just.

Clear up some confusion I'm, having on the stage 5.

Versus earlier stage phase III plan.

I thought I recall from last quarter that it was mainly an issue of how streamline a program you could get away with regards to using IV core Suva safety data and the FTA essentially saying by all means you can go ahead and do that but if you want to do that.

You need to stick with stage 5 and then you were going to try to convince them stage..4 makes sense also because stage 4 and 5 really are the same patient theoretically.

Right now I'm sure.

Hearing a little bit about incidents.

And these Burton question. So I'm wondering if these are part and parcel at the same issue or if I'm misunderstanding.

And then just also on that same program can you just remind us what have you told us that I might be forgetting about the phase III program.

In terms of the population and that study how much of that population was stage 5 and our stage 4 to 5 and what differential efficacy did you see and the phase II.

Thanks Arne.

And thanks for the question, so yeah, and now Youre not misunderstanding on the.

On the stage 5 and stage 4.

And information, we talked about last time, so the view.

Our the data we talked about last time was it.

Clear that stage 5 is very similar to hemodialysis patients actually based on published data out there.

And epidemiology data and what's not so clear and.

And what we think is going to become clear as we are looking at data that's emerging from our studies is stage 4 particularly late stage 4 patients.

And our very similar to stage 5 and.

In fact people don't spend a lot of time and stage 5 a lot of stage 4 patients may actually progressed right.

Hemodialysis, so we want to just.

Firm that up make sure we have all the statistics related to pruritus severity and incidents and both stage 4 and stage 5 and other words confirm that both stage 4 and 5 are very similar to hemodialysis patients, which is the argument we had made and nationally and therefore, the same and feel like.

Recommendation should should apply that we should be able to reference on the data we generated with <unk> injection and hemodialysis patients for as you know we have a significant number of safety exposures there.

Really a exposure levels that exceed those we see with oral <unk>.

And also maybe a possibility of referenced and the efficacy data related to both late stage 4 and stage 5 and that's that's the that's the exercise we have underway right now is gathering that information and then re engaging with the agency and the coming months to present that data.

And indicate that really yes, it's true that late stage and stage 5 look very similar to hemodialysis, but so based on the data with generally and so the late stage 4 patients and therefore, it would make sense to include them.

And any phase III program, and and I think we talked about this last time and it really from a logistical standpoint to run that phase III program across and efficacy period, only with stage 5 would risk losing.

Very many patients to hemodialysis. So so that's another part of the debate.

Discussion and we'll be having with the FDA once we have that once we have that dataset.

And then I've forgotten what your second question was yes the.

The second question was just if you could remind us I can't remember if you've told us before and I just forgot in.

And the oral <unk> stage 3 to 5 phase 2 and what was the representation and that study and what efficacy across the different studies and state. Yes. Yes. So you are right that that was a that was a trial that encompassed all priests dialysis and <unk>.

From <unk> through <unk>, 4 and 5.

Approximately.

The percentage of the patients and that study were 3 <unk> and <unk>, but as you know.

That is the majority of patients out there on the population and then and then the rest was stage 4 and stage 5.

In terms of.

Efficacy that is pursued a response.

And if.

And somewhat similar.

Across these stages in terms of drug response, what differs.

And between the early stage and the late stage.

Is that we see a higher placebo rate and.

Early stage CK D patients versus stage, 4 and stage 5 and Thats, probably because those early stage patients have more and more.

<unk> Pruritus response, there earlier and the disease process that don't have as consistent.

Our response so.

And 1 benefit if you like for us and moving to phase III and Derisking that phase III program, because as you are well aware and <unk>.

1 of the main issues with patient reported outcomes as controlling a placebo rate moving to stage 4 and 5.

Really going to be beneficial for us and are on our.

Late stage.

Graham and that we should be minimizing.

On placebo responses by focusing on the.

Patient groups subgroups that have the highest and most consistent per bed per.

<unk> responses.

Okay, and I apologize if I can just get clarification on your previous answer about determining how similar stage 4 and 5 pre dialysis patients are to dialysis do you mean in terms of there.

Perception and severity of their pruritus or do you mean in terms of the actual pathology and the debt.

The health of those patients so that.

For relevance and try to.

The mechanism of that mechanism of action from the the IV study and whether it should apply to the same yes, no I was actually essentially a bit of both but we are most interested and the pruritus severity and incidents between those 2.

And as you know, it's a continuum as not as and continue on for these patients. So so when we look at the data that's out there on the data, we're generating and certainly clear that very late stage 4 are very similar to stage 5 and as you know that pathology differences slight right for late stage 4.

To 5 so so that's that's the data we generate and we're going to use that and our discussion.

Okay, well I apologize for asking so many questions. Thanks, so much good luck non no problem. Thanks for the question on <unk>.

And again, if you would like to ask a question. Please press star 1 on your telephone keypad again debt as the star 1 to ask a question.

I'm showing no further questions at this time I would now like to turn it back to the car T for any closing remarks.

Okay. Thank you operator and.

Thank you everybody for participating in today's call I'd also like to thank the entire Cara team.

Our study investigators and.

Most importantly, all of the patients who continue to participate and our clinical trials.

We look forward to updating you again actually very very soon.

And thanks again for dialing in and have a good rest of the day.

Ladies and gentlemen. This concludes today's call. Thank you again for your participation you may now disconnect have a great day.

Oh no no no no no.

And.

[music].

Okay.

[music].

Good afternoon, and welcome to the car T Therapeutics second quarter 2021 financial results Conference call.

All participants are now in a listen only mode and there will be a question and answer session at the and please be advised that this call is being recorded at terrorists request.

I would now like to turn the call over to the Cara team. Please proceed.

Good afternoon. This is coal Hill Ferguson with Stern Investor Relations and welcome to Cara Therapeutics second quarter, 2021, and financial results and update conference call. The news release became available just after 4 P. M. Today and can be found on our website at Ww Dock Cara Therapeutics Dotcom and Mike.

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.

And then future regulatory and development milestones for the Companys product candidates, including the company's projected timeline for FDA review and potential approval and commercial launch of course, either injection for dialysis dependent and CK D. Dash AP the expected timeline for conducting meetings with the FDA concerning the Companys product candidates include.

Oral course, your vote for and D. D C K detached AP and a day dash 8 P and the potential for the Companys product candidates to be alternatives and the therapeutic areas investigated the potential impact of COVID-19 on the company's clinical development and regulatory timelines and plans and the company's expected cash reach because such statements are subject to risks and on.

Certainties 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 factors sections of the company's most recent annual report on form 10-K, and its other documents subsequently filed or furnished to the securities and Exchange Commission.

All forward looking statements all forward looking statements made on today's call speak only as of the date 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 date on which they are made.

Participating on today's call are Dr. Derek Chalmers, Cara, President and CEO and Mr. Thomas Riley Caris, Chief Financial Officer, I'll now turn the call over to Dr. Chalmers.

Okay. Thank you cole and good afternoon, everybody and thanks for joining us today on the call.

We have continued on to make significant progress across our development pipeline and the second quarter of this year.

With our NDA for our lead product candidate Christmas and injection for the treatment of moderate to severe pruritus in hemodialysis patients under priority review and our interactions with the FDA have progressed sufficiently.

And on schedule and through the completion of our late cycle growth here.

We remain on track for and expect to produce a target action date of August 23rd this year.

And in addition, we continue to make important progress across our oral cursive, our pipeline programs to that and and Q2. This year, we reported topline results from our phase 2 care dose ranging clinical trial of oral <unk> for the treatment of moderate to severe pruritus.

And atopic dermatitis patients.

Based on pre specified analysis of that dataset.

Identified the appropriate patient population and dose strength to move forward.

And pending the outcome of discussions with the FDA later this quarter and.

And initiate a phase III registration program and mild to moderate atopic dermatitis patients by year end.

We also plan to meet with the agency and the coming months to discuss the appropriate pre dialysis CK D patient population to move forward to phase III and that program and.

And we continue to enroll patients and our ongoing trials and both PBC and Natasha parenthetically with the aim of establishing pursue has efficacy across a range of patient pathologies per treatment of chronic pruritus remains a significant unmet need.

So the remainder of 2021 is shaping up to be truly transformative for the company.

And the potential approval and commercial launch of the first.

First therapy for the treatment of pruritus in hemodialysis patients and potential advancement of oral cursive ER into registration trials.

So what that and I'll, let me provide you with some additional details across our main pipeline programs.

Beginning with our most advanced program <unk> injection.

Following the Fda's acceptance of our NDA filing with priority review and the first quarter of this year, our dialogue with the agency has progressed well and without any review of delays.

Just on the outcome of our late cycle review last quarter. We currently do not anticipate and in manufacturing and inspection delays and we expect the agency to meet their particular target action date of August 23 of this year.

With that in mind, we remain focused along with our U S commercialization partner V for pharma for the commercial launch of <unk> and injection and the second half of this year.

As a reminder, based on V Force established U S. Neurology sales force and there are deep rooted relationships with both large and small U S dialysis organizations.

<unk> executed a strategic licensing agreement with V for pharma and the fourth quarter of last year for the commercialization of <unk> injection and U S dialysis clinics under a car 60% V for 40% profit share arrangement.

And we firmly believe this will support increased launch momentum and adoption of <unk> and the U S market if approved.

The financial considerations of the VFR agreement contribute significantly to the current strength of our balance sheet based.

Based on the terms of the license the company will be eligible to receive an additional $50 million common stock investment upon U S regulatory approval of true Suva injection.

And post launch.

Eligible to receive payments of up to $240 million and U S sales base commercial milestones.

And on Christmas Eve and injection reimbursement activity.

Ongoing interactions with CMS have been productive and we quantify on both our to dapper on.

And heck picks applications later in Q3 again, assuming pursue that injection approval.

Turning to ex U S. Commercialization planning we were also very pleased to announce earlier this year that the European Medicines agency accepted the MAA for day fell a careful and injection for the treatment of pruritus associated with chronic kidney disease and hemodialysis patients.

The EMEA will review the application under the centralized marketing authorization procedure.

And under our 2018 license agreement with <unk> Fresenius will be responsible for the commercialization of <unk> and injection across European territories with Cara eligible to receive tiered double digit royalty payments based on annual net sales and up to $440 million and tiered commercial milestones.

All of which are sales related.

The MAA is expected to render their decision and the second quarter of 'twenty 'twenty 2.

Turning now to progress on our oral Christian or the pipeline.

We recently announced topline results from the care of a phase II dose range and trial of oral <unk> for the treatment of moderate to severe pruritus and atopic dermatitis patients.

This trial you will recall was a randomized double blind placebo controlled study designed to evaluate the efficacy and safety of oral <unk> and 401 adult subjects with atopic dermatitis.

Patients were randomized to 3 tablet strengths of oral care, Suva, 255, and 1 milligram taken and B I D versus placebo for 12 weeks, followed by 4 weeks of active extension.

And as pre specified analysis.

Tests really significant change and the primary efficacy endpoint was observed and the mild to moderate that as BSA less and 10% patient population.

Which was evident at week, 1 and sustained through the treatment period.

In addition, a statistically significant improvement was also observed and the registration endpoint, a 4 point responder analysis and the mild to moderate patient population with 32% of <unk> treated patients achieving a greater than 4 point reduction and and our S. At week 12 versus 19% and the placebo group.

So these care results have provided key information related to the defined patient group that is mild to moderate and active dose range.

And in effect size on the registration and 4.8% responder endpoint from which to design appropriately powered phase III trials. So with this data in hand, and pending the outcome of our scheduled and a phase II meeting with the FDA.

We aim to initiate our first oral cursive, a phase III program and mild to moderate atopic dermatitis patients.

By year end 2021.

We also plan to present additional data on the additional analysis from the care trial at upcoming medical meetings later this year.

So to step back and think a little and in terms of ultimate potential positioning of oral <unk> and the atopic dermatitis treatment landscape.

It's clear that while pruritus is recognized as the definitive and indeed, the most burdensome symptom of atopic dermatitis therapy.

<unk> therapeutic development to date and this area has focused on pro inflammatory pathways.

Rather than perretta janick pathways.

And there is a particular treatment GAAP amongst mild to moderate atopic dermatitis patients, which is approximately 80% of the day population.

And our topical therapies do not adequately address chronic pruritus and systemic immuno modularity reagents are not available.

So based on its observed profile from our care dataset, we believe that oral cursive may provide clinical benefit for these patients and provide a systemic antipruritic therapeutic option, where non presently exists.

So moving on to our program and pre dialysis <unk> patients with moderate and severe pruritus.

The FDA has indicated the viability of stage 5 pre dialysis <unk> patients as a population for our phase III program and also indicated the potential to use the data from our previous trials of course, Suva injection and dialysis patients to support and approval based on a single phase III clinical trial.

We are currently gathering more data related to per at pruritus incidents and severity and pre dialysis <unk> patients and aim to meet with the agency and the fourth quarter of this year to further define a viable patient population for inclusion and a phase III.

Program.

Finally to our ongoing phase III trials in primary biliary cholangitis, and Natal, Jeff Heresthetic Huh.

Before I get to that I'd like to remind everyone that due to the ongoing COVID-19 pandemic.

And in accordance with the Fda's updated guidance for conducting clinical trials.

Pruritus is a common symptom of call a static liver diseases, 20% to 30% of these patients overall experience pruritus with that number rising to approximately 70% of patients with primary biliary cholangitis.

Our 16 week Phase II trial is designed to assess the safety and efficacy of a 1 milligram tablet strength of oral christova taken twice daily.

Versus placebo and PBC patients with moderate to severe pruritus.

The primary endpoint is the change from baseline and the weekly mean of the daily 24 hour worst itch <unk> score at week 16.

We now expect to report topline data from this study and the first half of 2022 due to delays and site initiations and patient enrollment, resulting from the ongoing COVID-19 pandemic.

Finally, with the goal of further establishing the broad antipruritic applicability of <unk> across patient populations with underlying pathologies.

Earlier this year, we initiated a phase II proof of concept trial Royal pursuit for the treatment of moderate to severe pruritus in patients suffering from Natalia Paris, Attica and neuropathic disorder.

<unk> by chronic pruritus and the upper to metal back the.

The phase II multi center randomized double blind placebo controlled 8 week study is designed to evaluate the efficacy and safety of oral <unk> and approximately 120 subjects with Natasha pilot silica randomized to receive oral pursue with <unk> twice daily versus placebo for 8 weeks.

By a 4 week active extension period.

Primary efficacy endpoint and has it changed from baseline and the weekly mean of the daily 24 hour washed etch and Rs score at week 8 of the treatment period.

And I am pleased to note today that this trial has now passed 50% enrollment Mark and based on our current recruitment rates, we expect full enrollment and less trial by the end of this year.

So overall our progress through Q2 in recent months has led defense laid the foundation for a very significant second half of 'twenty 1.

We very much look forward to the expected <unk> target action date later this month.

For <unk> injection as potentially the first FDA approved therapeutics for the treatment of pruritus in hemodialysis patients.

And we are well prepared along with our partner <unk> pharma for a commercial launch of <unk> and injection and the second half of this year.

With a strong balance sheet, we're well positioned to support our goal of initiating our first phase III program with oral <unk> and mouth and moderate patients by year end.

As well as continued to progress our ongoing oral programs and CK D and PBC and Natasha Parenthetic and patients and we will be updating you and all of the progress across these programs and the coming weeks and months.

So with that I'll now turn it over to Tom to detail the financial results for this quarter.

Thank you Derek.

As a reminder, the full financial results for the second quarter 2021 can be found in our press release issued today after the market closed.

Cash cash equivalents and marketable securities as of June 32021.

Total $207.4 million compared to $251.5 million at December 31, 2020.

The decrease and the balance primarily resulted from cash used in operating activities of $44.7 million per.

Partially offset by proceeds of $1 million from the exercise of stock options.

There was no revenue for the 3 months ended June 32021.

This compared to $5.6 million during the same period of 2020.

The company recognized $5.1 million of license and milestone revenue during the second quarter of 2020.

$4.5 million of which related to our license agreement with <unk>.

F N and CRP and <unk> 6 million of which related to achievement of the development milestone.

Related to our license agreement with CK day, pharmaceutical and pharmaceutical Corp.

The company also recognized zero point $5 million of clinical compound revenue and the second quarter of 2020.

And 2 mariucci pharmaceutical company and BFM CRP.

Research and development expenses were $25.2 million for the 3 months ended June 32021, compared to $26.1 million and the same period of 2020.

The lower R&D expenses in 2021 were principally due to a net decrease and costs associated with clinical trials and.

And stock compensation expense per.

Partially offset by a $10 million milestone earned by and tariffs from Biopharma. During the 3 months ended June 32021.

General and administrative expenses were $5.7 million for the 3 months ended June 32021.

This compared to $5.4 million and the same period of 2020.

The higher G&A expenses in 2021 were principally due to an increase and payroll costs.

Commercial costs and legal fees.

Partially offset by decrease and stock compensation expense.

Other income net zero point and 1 for the 3 months ended June 32021.

Compared to zero point $6 million and the same period of 2020.

The decrease and other income net was primarily due to a decrease in interest income, resulting from a lower yield on the company's portfolio of investments and the 2021 period.

Now turning to our finance guidance.

Based on timing expectations and projected costs for current clinical development plans.

<unk> expects that its existing on restricted cash and cash equivalents and available for sale marketable securities.

As of June 32021 will.

And will be sufficient to fund our currently anticipated operating expenses and capital expenditures into 2023.

Without giving effect to any potential milestone payments.

Our potential product revenue under existing collaborations.

I will now turn the call back over to the operator for Q&A.

Thank you at this time I would like to inform everyone in order to ask a question. Please press star 1 on your telephone keypad again that is star 1 to ask a question.

We have your first question from Jessica Fye with Jpmorgan. Your line is open.

Thank you for taking the questions.

Firstly can you talk about the timing for the recently announced API supplier agreement with BP and <unk>.

Is this typical day.

And closer look.

And does it affect the NDAA and anyway.

Yes, hi, thanks, Thanks for the question, it's a standard.

Commercial API supply agreement does not affect the Paducah date.

You have the NDA and any way whatsoever.

Okay.

And on the orderly program in non dialysis setting.

And do you expect to initiate dosing 18 build on.

Will you wait till they have near D C and Jennifer and close up earlier stage patients and the trial will you.

To start it is secured debt.

No. So so presently we're gathering.

Both patient data and we have physician research underway.

In relation to incidents and severity of severity or provide us.

In pre dialysis.

CK D patients.

And once we've gathered that information Philly.

Our plan is to engage with the FDA probably in Q4 of this year.

To get and agreement on a viable pre.

Dialysis <unk> population for inclusion and that phase III program. So it's likely that that would initiate.

Early in 2022.

Got it thank you.

Thank you very much.

We have your next question from Chris Howerton with Jefferies. Your line is open.

Great Congratulations.

Setting times for carrier Thanks for taking my questions.

Again, thank you for any debt.

Yeah of course, so for the I guess what are the maybe following up on the.

Added criteria for the oral CK day program was.

The sense that the FDA did not feel like there was unmet need and in less severe patients and stage 5 or was it.

Simply the case, where there was insufficient information and make that kind of a judgment call. I guess is 1 question and then the second question I had Derek was.

Related to the <unk>.

Atopic dermatitis program I think I feel like you described this last time, but if you could just remind us what it is that you'd like to align with the FDA with respect to that program is there something.

In addition to what you've described to US here in terms of going after the mild to moderate and the dose range that you believe to be active.

Right. Thanks, Chris.

Let's start with your <unk> question and I feel it is the latter of your 2 options and in relation to the FDA there just.

There is a lack of information presently in relation to pruritus and incidents and the severity of that and earlier stage <unk> patients relatively speaking towards.

In relation to stage 5 which is obviously the final stage prior to hemodialysis. So.

With that in mind, our view has been and we are.

And I'm perfectly develop and that information.

And collaboration with the National Kidney Foundation, we're running patient research.

And also run and physician research and we aim to get if you like.

And more recent more up to date and information we can use there to define the breath of the pruritus issue and.

And the pre dialysis <unk> population that we can then use as a.

Basis for a discussion with the FDA and relation to to where we define that population for inclusion in the phase III. So it's really a <unk>.

Filling the gap in terms of lack of available information if you like real time and those and those are populations that we have underway.

So that's that's the progress there and as I said, we aim to have that meeting with the FDA and the coming months to define that.

In terms of the in terms of a day I'm not quite sure what you're getting out there our view on the <unk> program is we're looking for.

Looking for a label to.

And to treat moderate to severe pruritus, specifically within mild to moderate patients.

Patients that are in need of <unk>.

Systemic anti periodic.

Therapy.

And our view view there is that based on our phase II data, we certainly see and appropriate profile profile from monotherapy.

That we can significantly reduce pruritus.

The rapid onset.

We have a very attractive safety profile for the drug.

And so so that's the basis of our.

And the phase 2 briefing book and I would like to see that program progress with the agents got it.

Okay. So it simply got it okay alignment on trial design and the final regulatory path exactly exactly you know how that goes.

[laughter].

Always crystal clear.

I guess, maybe if you wouldn't mind just a quick follow up to maybe my previous question is there do you have what have you.

And disclosed about your view of the epidemiology of the stage 5 patients that would experience moderate to severe pruritus.

Wow.

Just on the data and said there is some published did add though you could find tress and theirs.

Adopts analysis to adopt surveys, we cannot severity and frequency and pretax free hemodialysis CK D patients and it's certainly clear that the severity of the pruritus increases with the severity of <unk> disease.

No.

What we are looking at and again and to CNR analysis is.

Somewhat similar frequency and stage 4 and stage 5, particularly later stage 4.

And and.

As you know.

The debate and lines between those are somewhat arbitrary it seems clear that physicians really.

Regardless, we got the patient in terms of late stage versus earlier around these defined threshold vs. Egfr definitions and from their analysis and their feedback is clear that they regard pruritus is a significant issue and late stage pre dialysis <unk>.

D patients. So we're just trying to put some parameters around that population and so we can define that.

And more accurately and then and then talk to the agency again.

On what should be included.

Okay.

Very clear and I appreciate the added color, okay, well, thanks, Derek I appreciate and congrats question and answer the questions.

We have your next question from David and Colin with Piper Sandler Your line is open.

And thanks, just a few so first on <unk>.

Apologize if I missed this but is the F D. A onboard with the definition of mild to moderate per the body surface area being under 10% I mean is that something where there could be and potential for daylight between.

Between you and and the agency just just give me a refresher.

And on that in terms of the mild to moderate definition. That's number 1 number 2 is and liver disease.

I guess the question here broadly is to the extent that you do show a signal in phase II, how wide of a population would you assess and a phase III.

Program.

Would it be primary biliary cholangitis or something.

Something more broadly and patients with hepatic impairment.

And then thirdly and non <unk> silica.

Just I guess.

And maybe getting into my excuse here, but to the extent that you have a signal and that study.

What does a phase III program look like do you have to run 2 identical phase III studies.

And I realize it's a new indication so maybe just help us understand how you would think about that to the current U move forward. Thanks, Yeah.

Yes, Thanks, David.

3.4 for you as well it was well played.

On a day yet the definition of amount tomorrow, PSA less and 10% is pretty much standard on.

And that they may add some iga criteria to that but that's a that's a standard.

Definition for mild to moderate disease based on the extent of lesions and those patients that don't.

Thats contentious based on what we see on other labels out there and as you know.

It's a standard regulatory path label specific for mild to moderate patients that's not and if a new for.

For the for the agency.

So that's that 1 on liver disease.

PVC and I think we've had this discussion before.

Generally the reason you're entirely correct the pruritus is.

Broadly and issue across.

Cola static liver diseases, and a number of other.

Liver related disorders and.

The reason we went for PVC initially as the incidents there and.

And the severity is certainly higher than in other liver diseases.

And close to 70%.

So that debt that we regard it as.

Unimportant parameter for enrolling patients that we wanted consistency and the pruritus, we've left desk and long enough and a superior patient reported outcome and 1 of the issues and control and placebo rates here is not to other and consistency and.

And Europe Pruritus response, so so that was the reason to use PVC as of course, and orphan indication and thats somewhat better a little bit and that it's much more difficult to recruit and there are certain centers, we'd like to get in there which have been difficult to get to.

Because of the Covid restrictions.

And that's a pity, but I think if we can push on here and we're gonna see on uptake and and our patients. There are soon and of course, we have high confidence and the mechanism for.

Qatar and that particular disease situations since we already knew that now fewer fee and got that label extension and Japan, you'll recall after the initial label for hemodialysis associated price. So we have.

A high conviction that this is a mechanism that should be effective here ultimately run and a phase III program and PVC is unlikely for us I think if we move into phase III program on that.

It'll be a strategic decision when we get there in terms of.

What we're seeing and these other.

Patient populations is likely to be a broader liver disease population. So that we can actually run that program and on inappropriate timeline.

So that's the view on liver disease, where really use and PVC is.

See if you like as the efficacy and the liver disease situation and it somewhat similar.

Natasha Pyrostat it cannot.

We think this is a it's.

And as have interest and an indication per se with with probably dependent on which estimates you want to believe run will probably run a million patients.

And the you asked very common posts to age 65, and and really nothing available again.

For those patients and I can.

Can tell you the entry.

Scores, we're seeing and these patients coming into that trial.

And are on the severe and moderate to severe so this is a significant.

Cynical issue for those patients again.

And that is a kind of a proof of concept patient growth to cover the neuropathic etch area. It's a large.

There's a large patient population and estimated at some 8% of all the chronic pruritus and the U S. So we wanted to make sure again and we have a mechanism that's going to be applicable for if you like a nerve related.

Disorder that induces pruritus, so so thats, where used and as our model population.

Again, we're again, we'll look at the ultimate data and decide whether we push forward here and to phase III is actually been surprisingly rapid enrollment here, which probably speaks to the size of the patient population and again, if we look at us at the end of the day and that makes sense in terms of timeline to a label.

And that might be something that might be something we'd consider it but at this point.

And we are interested in getting our first phase III and it looks like it's going to be and atopic dermatitis, and then making sure confirming efficacy.

From all these other patient populations and then we will decide which of those makes sense to push forward into larger trials. Once we have all that data.

Does that answer your question David.

Okay.

There are start aligning yourselves.

No no no I'm here I'm, sorry, I'm, sorry, I was on mute, but yes, no that's very helpful.

Okay.

David Thanks for your questions.

Again, if you would like to ask a question. Please press star 1 on your telephone keypad again that is star 1 to ask a question.

We have your next question from Jason <unk> with Bank of America. Your line is open.

Hey, guys. Thanks for taking my questions.

And I guess first question Derek how do you envision and the ramp of a drug like <unk>.

And the first <unk>.

6 months to a year and.

And the dialysis setting.

Sort of curious as you've looked at other products and the setting like ours. The Bev just sort of curious if you see a faster ramp.

Cautious early flow Trialing, and then sort of a buildup.

After the first 12 months.

And just sort of curious and I guess it had some implications for how the bundle could ultimately reset depending on utilization and cost.

And then my other question. There is there is some free off city and the investment community about the potential impact of Super responders and the.

On trials.

Our debt.

Alex I will comment on other on.

Unfavorable FDA outcomes and that.

And our space.

Just curious if you can.

Address that and your comfort level around those dynamics.

Thanks, Jason.

Thanks for dialing in so in terms of in terms of ramp and <unk> and Jason and I think we've had desk and a general discussion before but.

It is an unusual market highly consolidated and the U S. As you know.

And with the vast majority of hemodialysis patients covered by 2 dialysis organizations.

Utility of the drug there and protocol adoption of the drug there is.

As highly important to success ultimately, which is 1 of the reasons we.

We decided to sell on our initial agreement with <unk> Fresenius and as you know and recall from that part of that agreement as we have a 50.50 <unk>.

Profit split within Fresenius clinics, so and Youre correct looking at other drugs that have launched recently and that space parse a bev of course being the only example of a drop through to DARPA. Yeah. There was a rapid adoption there and we do see significant uptake and the first and the first year and.

And certainly 2 years and as you know.

It's important for any drug and that space and Thats, where we want to assess utility for future reimbursement.

Post the dapper. So so looking at if you like V Force track record here.

With drugs, such as from ourselves and that space and they've certainly had great success with with rapid uptake and I do think the uptake curve and that particular market space is going to look different than a standard PCP space, we do anticipate a faster and faster ramp.

With the pursuit of and Jake.

And but good question, yet unusual market dynamics there.

<unk>.

And then in terms of the.

In terms of the dataset, we've used and our and our NDA for efficacy confirmation and now we're very comfortable with that and certainly based on the interactions we've had with the FDA.

And our late cycle meeting I don't think we're going to have any issues in relation to the dataset, we've used that from both <unk> and <unk>.

With that submission.

Okay.

Okay. Thank you.

Thanks, Jason.

We have your next question from GAAP <unk> with Stifel. Your line is open.

Hi, This is Jack I'm, calling in for Annabel <unk>. Thank you for taking our question.

So a few things related to the SKU per day for IV course universe at this month.

And what types of commercial activities are your partners pursuing at this time to prep for launch.

And what priority will be 4 be positioning this and their portfolio.

And what work has been done ahead of time.

The paducah to file for the Apple payment from BMS is that something that can be done ahead of the approval or not.

And additionally.

Just for some clarification with the phase 3 a day trial.

What kind of option and you expect to propose to the FDA as far as design adjustment.

Outside of just tailoring to the mild and moderate population do you feel like there are other modifications you can make to improve the statistic.

Great Jack.

Thanks for the questions thanks for dialing in and so.

Let me I think I got all of those but let me start with the <unk>. So I think as I said on the call we still expect per day.

On August 23rd in terms of preparing for commercialization and as I said on the call we will be assuming approval.

On August 23rd we'll actually be filing both are to DARPA and <unk> applications. The following month.

So all of that is and preparation of approval and will be underway that months.

In terms of other commercial prep and.

And with <unk> 4 and in combination with vs..4.

And there'll be a lunch and dinner.

Disease state awareness.

This quarter and actually into Q4 ahead of reimbursement.

We are constantly talking with CMS and terms of reimbursement post to DARPA and that's been very productive and we will continue and <unk> is working with large dialysis organizations of course some of them. They are very intimately.

And related to and mid sized dialysis organizations on optimizing.

Formulary and protocol placement.

Once we get pursue and injection approval.

You will see launch activities at the upcoming ASN and.

<unk> meeting in November related to pursue and injection and I certainly know that the 4 has rep training well underway and are planning for a launch meeting and.

I think that covers your questions on on pursuit of injection jackpot.

Correct me, if I'm wrong and then your last question was.

And phase III.

Trial design, and how we see positioning on that within the patient population and our view there and again, it's based on empirical data and as I've said and our.

And on a pre prepared remarks, we had no 1 less was a heterogeneous population when we initiate that phase II phase III trial.

We pre specified where we're going to look at efficacy both in mild to moderate patients, which obviously have a different.

Pathological presentation and actually different systemic immune profile, then moderate to severe patients and thats clear.

And that we have a drug that shows.

Its greatest efficacy and the mild to moderate population. So and we will also be presenting more data from that study a little later this year, which I think will help you and thinking about the Jack in terms of other endpoints, both quality of life and pathology and points that will be presented there.

But we think we are very confident on where we think this drug works works best.

And that said and the mild to moderate.

Patient population, which as you know is a defined.

Patient population for for for labeling.

For the FDA. So so that's the possession and we're gonna proposed when we meet with the agency.

Great. Thank you so much that's very helpful.

Thank you Jack.

Okay, and if you would like to ask a question. Please press star 1 on your telephone keypad again. This is par wanted to ask a question.

We have your next question from <unk> <unk> net with H E. H C. Wainwright your line's open.

Hi, I have a couple of questions around the oral <unk> pre dialysis program can you just.

Clear up some confusion I'm, having on the stage 5.

Versus earlier stage phase III plan.

And I thought I recall from last quarter that it was mainly an issue of how streamline a program you can get away with regards to using IV course, Suva safety data and the FTA essentially saying by all means you can go ahead and do that but if you want to do that.

And you need to stick with stage 5 and then you were going to try and convince them to stage 4 and makes sense also because stage 4 and 5 really are the same patient theoretically.

Right now and.

Hearing a little bit about incidents and.

These Burton question. So I'm wondering if these are part and parcel at the same issue or if I'm misunderstanding.

And then just also on that same program can you just remind us what have you told us that I might be forgetting about the phase III program.

In terms of the population and that study how much of that population was stage 5 or stage 4 to 5 and what differential efficacy did you see and that phase III.

Thanks, Sean and.

And thanks for the question, so yeah, and now Youre not misunderstanding on the.

On the stage 5 and stage 4.

And information, we talked about last time, so the view.

Our the data we talked about last time was it is clear that stage 5 is very similar to hemodialysis patients.

Actually based on published data out there.

And epidemiology data and what's not so clear and.

And what we think is going to become clear as we're looking at data that's emerging from our studies is stage 4 particularly late stage 4 patients.

Very similar to stage 5.

In fact people don't spend a lot of time and stage 5 a lot of stage 4 patients may actually progressed straight to hemodialysis. So we wanted to just.

Firm that up make sure we have all the statistics related to pruritus severity and incidents and both stage 4 and stage 5 and other words confirm that both stage 4 and 5 are very similar to hemodialysis patients, which is the argument, we'd made and nationally and therefore, the same and feel like.

Recommendation should should apply that we should be able to reference all the data we generated with <unk> injection and hemodialysis patients as you know we have a significant number of safety exposures there and.

Really a exposure levels that exceed those we see with oral <unk>.

And also maybe a possibility of referenced and that efficacy data related to both late stage 4 and stage 5.

That's the that's the exercise we have underway right now is gathering that information and then re engaging with the agency and the coming months to present that data.

And indicate that relates yes, it's true that late stage and stage 5 look very similar to hemodialysis, but so based on the data would generally and so to late stage 4 patients and therefore, it would make sense to include them.

And any phase III program and I think we talked about this last time and it really from a logistical standpoint to run that phase III program across and efficacy period, only with stage 5 would risk losing.

Very many patients to hemodialysis. So so that's another part of the debate.

And discussion we will be having with the FDA. Once we have that once we have that dataset.

And then I've forgotten what your second question was yes the.

Second question was just if you could remind us I can't remember, if you've told us before and I just forgot.

And the oral <unk> the stage 3 to 5 phase 2 and what was the representation and that study and what efficacy across the different studies and state. Yes. So yes. So you're right that that was a that was a trial that encompassed all priest dialysis <unk> subgroups from 3 a true <unk> 4 and 5.

Approximately 50% of the patients and that study were <unk> and <unk>, but as you know that estimate majority of patients.

And out there on the population and then and then the rest with stage 4 and stage 5.

In terms of.

Efficacy that is pursued a response.

And it's somewhat similar across these stages in terms of drug response what differs.

The early stage and the late stage.

Is that we see a higher placebo rate.

And early stage CK D patients versus stage, 4 and stage 5 and Thats, probably because those early stage patients have more.

And Im labile Pruritus response earlier and the disease process that don't have as consistent.

Response so.

And you know 1 benefit if you like for us and moving to phase III and Derisking that phase III program, because as you are well aware on 1 of the main issues with patient reported outcomes as controlling a placebo rate moving to stage 4 and 5 is actually going and be beneficial for us and on a lag.

And stage program and that we should be minimizing.

Average placebo responses by focusing on the.

And the patient groups subgroups that have the highest and most consistent per bed.

Paretic responses.

Okay, and I apologize if I could just get clarification on your previous answer about determining how similar stage 4 and 5 pre dialysis patients are to dialysis do you mean in terms of there.

Perception and severity of their pruritus or do you mean in terms of the actual pathology and the.

On the health of those patients so that.

For relevance.

The mechanisms that mechanism of action from the IV study and whether it should apply to the Saint Pete and I was actually at essentially a bit of both but we are most interested and the pruritus severity and incidents between those 2 growth.

And as you know is a continuum as not as and continue on for these patients. So so when we look at the data that's out there on the data, we're generating and certainly clear that very late stage 4 are very similar to stage 5 and as you know that pathology difference is slight right for late stage for.

And to 5 so so that's that's the data we generate and we're going to use that and our discussion okay.

Okay, well I apologize for asking so many questions. Thanks, so much good luck non.

No problem and thanks for the question on <unk>.

And again, if you would like to ask a question. Please press star 1 on your telephone keypad again star 1 to ask a question.

I'm showing no further questions at this time I would now like to turn it back to the car team for any closing remarks.

Okay. Thank you operator and.

Thank you everybody for participating and today's call I'd also like to thank the entire Cara team.

Our study investigators and.

Most importantly, all of the patients who continue to participate and our clinical trials. So.

And we look forward to updating you again actually very very soon.

And thanks again for dialing in and have a good rest of the day.

Ladies and gentlemen, this concludes today's call. Thank you again for your participation you may now disconnect.

Good day.

Q2 2021 Cara Therapeutics Inc Earnings Call

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