Q4 2019 Earnings Call
Good afternoon, and welcome to Cara Therapeutics fourth quarter and for year 2019 financial results Conference call.
All participants are in listen only mode.
There would be a question and answer session at the end.
Please be advised that this call is being recorded.
Curse request I would now like to turn the call with Securities. Please proceed.
Good afternoon, it's a job holding Smith, but stern Investor relations and welcome to care Therapeutics fourth quarter and full year 2019 financial results.
The conference call.
It is really became available just after four P.M. today can be found on our website at www Dot care therapeutics Dot com.
You May also listen to a live webcast and replay of today's call on the Investor 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 ongoing clinical trials.
Actual results of ongoing clinical trials timing of future regulatory and development milestones for the company's product candidates, including the company's projected timeline for the submission of its first and D.A. <unk>.
Potential for the company's product candidates to be alternative in the therapeutic areas investigated and the company's expand it didnt catch 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 art.
Described more fully and care therapeutic filings with the Securities and Exchange Commission, including the risk factor section of the company's most recent annual report on form 10-K, and other documents subsequently filed with or furnished to the securities and Exchange Commission.
All forward looking statements made in 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 were made.
Participating on this call our Derek Dr., Derek Chalmers, carrot, President and CEO and Mr., Rick Macaire, VP and head of counting I'll now turn the call over to Dr. Chalmers.
Thank you Jay good afternoon, everybody and thanks for joining us on the call today from 2019 was certainly a very significant unproductive year for Kara.
As we advance the late stage clinical development of our lead candidate cursive across a range of credit clinical populations.
In may of last year, we announced positive top line results from our come one pivotal phase three trial of cursive injection and hemo dialysis patients with moderate to severe chronic kidney disease associated pruritis or CKD HP Dell.
Phil results from this trial were published in the New England Journal of Medicine in November of last year.
In December of last year, we identified the appropriate tablet strength of oral cursive to bring forward into a phase three registrational program and no one hemo dialysis patients with CKD associated provide us following positive topline results from our doors ranging phase two trial and.
Yes patient population.
We also expanded our oral Chris is our clinical development program into two new poetic indications with high unmet need.
The topic dermatitis, and chronic liver disease associated provide us and we initiated both of those phase two trials and the middle of 2019.
Lastly, we made important corporate advances in 2019, we strengthened our financial position with a public follow on offering of approximately $136 million. We also entered into a commercial license agreement with the interest bio pharma for oral formulation rights to its peptide allergens.
Technology to develop and commercialize oral pursue the and any indication.
Building on this momentum from 2019, we expect multiple major clinical data read outs and regulatory advancements in 2020 and on the call I'll provide an update on each of our programs and what we expect for the rest of this year.
Before we dive into those programs as a quick reminder, on creative as broad anti pruritic mechanism of action, which as in contrast to other modalities that focus on blocking one specific credit Jen.
Such as NK, one antagonist, which have been in the news this week.
The action of courses on do I'm on epidermal immune cells blocks the release of the range of nerve sensitizing molecules infrared engines.
And of course, it about directly diminishes the stimulation abdominal century fiber is principally see fibers downstream from the action of the poor antigen and it says do own ivano, an anti inflammatory effect that we believe provides for onto poetic activity, regardless of the initiating pathophysiology weather.
That's chronic kidney disease, chronic liver disease or some type of dermatological conditions.
Okay. So let's begin with our lead program for cursive injection and hemo dialysis patients with CKD associated Pruritis. This pivotal program includes four phase three studies Cam Wanna U.S. efficacy trial, which we had a positive top line data last year come to our global efficacy trial.
Which which we expect topline data from in the second quarter of this year.
To open label safety trials.
Income one we observed a robust sustained anti pruritic effect of CRE Suva over the three months treatment period cursive injection met the primary endpoint significantly reducing reducing itch intensity with 51% of subjects achieving at least a three point improvement and worst itch intensity.
I'd.
Or an IRS compared to 29% of subjects and the placebo group.
The trial also met all secondary endpoints and in addition, cursive I was generally well tolerated what the safety profile consistent with prior clinical trials.
Like calm won our ongoing global come to trial, which is was designed to investigate the efficacy of cursive injection that adores, a 0.5 micrograms per kilo versus placebo and this is administered three times per week after schedule dialysis sessions over the 12 week treatment period.
And I told where of last year, we announced an increase in target enrollment for come two to 430 patients about a 20% increase from the original target of 350 based on the recommendation of the independent data monitoring committee to maintain a pre specified conservative.
Testicle power for the primary endpoint.
Come to was fully enrolled to this level in December of last year.
And we expect topline data from this trial and the second quarter, followed by the submission of our first new drug application for consumer injection and the second half this year.
In terms of safety exposures. We currently have a safety database in line with IC H. guidelines for India submission with over 1500 total patient exposures with more than 600 patients completing six months of treatment and over 300 patients completing one year of continuous treatment.
As you know from these calls CKD associated providers is an area of high unmet need.
No therapies currently approved in the U.S. or Europe.
Part of the National Kidney Foundation, there are over 500000 dialysis patients in the U.S. with 60% of these patients reporting some level of providers, 40% to 50% and the moderate to severe range. So clearly a significant unmet need we do intend to commercialize cursive injection.
And in the U.S. and we've established commercial license agreements and the other major commercial markets, including Japan, South Korea, and the European Union.
And the he do we have a collaboration with before Fresenius, which allows us to leverage the broad reach a fresenius to dialysis patients across Europe.
And we also believe that's collaboration positions us well for commercial success in the U.S.
Well, we've established a co promotion and profit sharing agreement with before Fresenius, specifically within Fresenius clinics in this country that allows us to utilize a the nephrology focused expertise of Fresenius and we expect helped build momentum for the adoption of cursive injection upon.
Launch.
So as we advance cursive injection to an N D. A filing in the second half this year.
Pending our positive comp to results. We have also initiated key pre commercial activities. The cross functional groups it kinda, including medical affairs, commercial and C.M.C., where we've already established the supply agreement for commercial scale manufacturing.
So that's where we stand in terms of cursive injection development and we'll continue to update you on a commercial preparations as we approach the N D filing and beyond.
Near term of course, we're very much looking forward to come to phase three results and the next couple of months.
So let's move onto our pipeline programs focused on oral Chris Uh Huh, let's start with our lead program in pre dialysis CKD patients with moderate to severe provide us.
Based on Pruritis related drop dropped prescription data of the approximately 7.3 million people diagnosed with CKD here in the U.S., but 33% are currently receiving some sort of treatment for provide us.
These treatments typically include generic antihistamines or corticosteroids, neither of which effectively alleviate the provided spurred in long term. So this is a large again patient population with significant unmet need.
In December of last year, we reported positive topline results from our 12 week.
These two trial evaluating the safety and efficacy of three tablet strand Savoro courses <unk> 0.25 milligrams 0.5, and one milligram once daily.
Based on the data we identified the one milligram tablet strength of oral cursive as a dose level to take forward into phase three and we're pleased with the clinically meaningful responses, we observed in patients treated with oral pursue.
Patients treated with us doors that that's doors achieved the primary endpoint of a statistically significant reduction and the weekly mean of the daily worst itch intensity scores at week 12 in terms of responder analyses. We also observed 72% of patients on the one milligram dose achieved a three point agreed or improve.
<unk> from baseline and the weekly meeting of the worst such intensity scores and this was compared to 58% of patients on placebo barely messaging statistical significance looking at the higher threshold complete respond or level, Mrs that proportion of patients exhibiting worst thick and our S values.
One or zero and the final week of treatment all three tablet strengths of courses are exhibiting dose dependent statistically significant improvements over placebo with approximately 40% of patients at the one milligram level exhibiting a complete response versus 14%.
On placebo.
Lastly, and of course importantly, oral cursive was generally well tolerated with the safety profile consistent with that scene and our earlier pursue the clinical trials.
So having successfully identified the tablet strength to take forward for this indication we plan to hold an interface to meeting with the F. D to enable the initiation of a pivotal phase three program and the second half of this year.
In 2019, we also initiated phase two trials for the treatment of courageous and two additional patient populations you topic dermatitis on primary biliary cholangitis or PBC and we do them to see topline data from both of these trials leader and 2020 in January.
We have this year, we expanded our phase two trial any topic dermatitis patients to include approximately 320 adult patients with moderate to severe provide us from 240, and we incorporated an interim conditional power assessment into the design to be conducted again after approximately.
50% of the targeted patient number complete the designated 12 week treatment period.
Based on that current sample size and our ongoing enrollment rates, we do expect to complete the interim statistical analysis for this trial and the second quarter of this year.
And this trial in terms of design subjects were randomized three tablet strengths of oral pursue the 0.25 0.5, and one milligram taken twice daily versus placebo. The primary efficacy endpoint is the change from baseline and the weekly mean of the daily 24 inch worst in Iran score at week.
Well for the treatment period and secondary endpoints include the proportion of patients achieving improvement of from baseline of at least four points as well as change from baseline and each h. related quality of life scores.
End of week 12.
So overall our progress in 2019 has laid the foundation for a very significant year ahead, Cara, we expect several important clinical and regulatory milestones in the year ahead, starting in the next quarter with topline data from our pivotal come to seize through trial.
Which of course is going to enable filing over first and D and the second half of this year. So we do look forward to updating you on all the progress across all these programs and the coming quarters and with that I'll turn the call over direct to cover the financial results for the quarter and also for the fiscal year.
[noise]. Thanks, Derek as a reminder of the full financial results for the fourth quarter and full year 2019 can be found in our press release issued today after the merger closed.
For the year ended December 31st 2019, we reported net loss of $106.4 million $2.49 per basic and diluted share compared with net loss of $74 million for 2006 cents per basic and diluted share for 2018, but fourth quarter of 2019, we reported net loss of 28.6 million.
Dollars.
Or 61 cents per basic and diluted share compared to a net loss of $20.7 million were 52 cents per basic and diluted share for the same quarter of 2018.
Revenues for the year ended December 31, 2019 were 19.9 million compared to 13.5 million in 2018 revenues in 2019 in 2018 were primarily related to a license agreement with before percentages revenues in 2019 in 2018 also included 140003rd.
The $3000, respectively from the sale of clinical clinical compound to Maruishi.
In the fourth quarter of 2019.
We recognize revenue $4.5 million related to the before for Senese collaboration agreement compared to 5.5 million during the same quarter in 2018.
Research and development expenses were 113.8 million for the year ended December 31, 2019, compared to 75.5 million in 2008.
Higher R&D expense in 2019, principally due to net increases in clinical trial costs increases and stock compensation expense payroll and related costs as well as expense in connection with the in tears license agreement in 2019.
For the fourth quarter, we reported R&D expense of 29.9 million compared to 22.8 million in the same period of 2018.
R&D expenses in 2019, principally due to a net increase in cost associated clinical trials as well as increases in payroll and related costs.
Gina expenses was $17.7 million for the year end of December 31st 2019, compared to 15.3 million in 2018.
The increase was primarily due to increases in stock compensation expense payroll and related cost consultant costs legal and accounting fees insurance cost and franchise taxes. Those increases were partially offset by decrease and utilities.
Gina expenses were rope relatively consistent at $4.6 million during the fourth quarter of 2019 compared to $4.7 million in the same period of 2000 feet.
Other income was $4.5 million for the full year 2019, compared to 3 million in 2018.
Increase was primarily due to higher average balance of our portfolio of investments in 2019.
Other income was $1.2 million in the fourth quarter, both 2019 and 2018.
As of December 30, Onest, 2019, or cash cash equivalents in marketable securities totaled $218.2 million.
Compared to 182.8 million at the end of 2018 increase primarily resulted from hundred 36.5 million of cash raised in a follow on offering are common stock in July 2019.
$6.1 million received from the exercise of stock options, partially offset by $109.2 million of cash used in operating activities.
Turning to our financial guidance.
Based on the projected cost for a clinical development plans and timing expectations. We expect their current cash cash equivalents in marketable securities as of December 31st 2019 will be sufficient to fund or operations into the second half 2021, not accounting for any potential milestone payments under existing collaborations I'll now turn the call back.
The operating for acuity.
Thank you, ladies and gentlemen, as a reminder to ask the question.
The press Star then one on your telephone.
To withdraw your question.
Again, it's thought I want to ask the question.
Please standby we've compiled the culinary roster.
First question comes from a lot of Chris Howerton with Jefferies. Your line.
Excellent.
Thanks for taking my questions and of course, congratulations on another quite a quite a year last year.
So for me Derek I think just a couple of questions primarily related to the pipelines so quarter.
CKD oil CKD program and you.
Does the results are what they are what.
Do you hope to get it in terms of alignment with the FDA and have you kind of thought anymore about what the ultimate primary endpoint you think will.
Be either received by the investment and clinician community that we'll get that.
The best reaction.
Okay, Chris. Thanks, I thought you were going to bid on additional question. It was that one question. One long question, though do you have or was that too.
That was one long question I like to hear myself, because you know, yes, yes, as a a like those mellifluous tongs as well so under CKD oral you know as you know we were pleased with that data we had our primary endpoint.
It was a study designed to identify the optimal dose strengths to take forward than we did so and you know in terms of endpoint definition as you know we spent a long time on this in terms of or hemo dialysis patient analysis.
Centrally end stage CKD and when we look to that actually in consultation with the F.D. as we discussed the designation of breakthrough Fukushima, we actually I'm perfectly to go data and looked at clinical meaningfulness in terms of reduction and worst a generous score for that patient class.
I'm not number as you know as you know as a little less than three point and we were nice enough with our F D.
Plans to run that up to three point and that certainly is a clinically meaningful reduction for CKD patient within our S. Scores. So so that would be our proposal as a primary endpoint going forward with a with the CKD oral study now we also as you know have a range of secondary endpoints were interested in there and.
We would look at most likely higher threshold responder analysis, there and perhaps the wait wait.
But as far as we have determined again and perfectly.
And part of our consultation with the F.D.A. a three point responder.
Analysis does is the threshold for clinical meaningfulness there.
Sure and.
So then the outside of perhaps the primary endpoint are there other and.
Yes, I'm, putting words in your mind, you know, but what what would you like to gain a line with on the F.D.A. during that meeting or what are the things that you think need to be worked out.
Well you know you've hit the nail on the head right, Chris what we want agreement on our registration endpoint and our proposal based again on or analysis for CKD patients would be a three point responder.
Yeah, and we would most likely look at four point beyond that as well as our usual quality of life managers and that's that's the main goal at least from the clinical portion of our into phase two meeting with the FDA.
Got it Okay and is there the other topic of discussion with respect to the oral CKD program has been the perhaps higher than expected placebo response or view given any additional thought in terms of how you expect to control that in a further trials.
Yes, we have you are not be surprised to hear Chris we have thought about that.
More than one occasion, we sure so so but let me say right off the but you know the aim of this phase two trial of course is to be able to obtain empirical data and the patient population, we want to examine phase three and actually based on our proposed endpoint use that data to power the phase.
We appropriately even to overcome watch.
We think based on our past experience in this patient population is an unusual anomalous placebo response. So that's the first thing to say you know we have the data now that we can power that trial appropriately and even if we are you know off the market in our proposed measures to reduce that placebo response, we still.
We'll have an appropriately powered trial unless you know we're very fond of running.
Interim analysis to make sure we're on track and our larger trials. So that is our overall approach or that's how we're going to solve that's if you like to view as one problem, but again, we have thought about that in terms of other elements, we could adopt into the phase three that should help the c. The placebo response, we believe and we've mentioned that's been.
Before we do believe there certainly was the potential.
For some expectation bias in these patients so a lot of the the sites we use the clinical sites, we used in our oral cursive a trial where sites that had previously participated intrusive injection trials.
Hemo dialysis patients to the was experienced with the drug, albeit in a different formulation and the end stage. If you like for that particular patient population, but certainly that could have been a possibility and the solution. There was somewhat obvious we're going to use de novo sites that haven't had previous experience with a drug. So that's one thing we can easily adopt.
We're also looking at the possibility of use no longer run in period, you know it's possible that these earlier stage CKD patients, perhaps they have more labor I'll provide us a that me waxed and waned a little more than end stage patients and so to identify the more consistent predications, we can incorporate a lot.
Longer run in period, which is easily and corporate didn't and finally by nature of the very design of the phase three looking at one optimal dose versus placebo in one to one randomization that alone should reduce the placebo response from the the designed three to one randomization we used in the phase two trial. So certainly we're gonna.
I have that as part of our design. So those are all.
Those are all easy elements, we can change that should help the placebo, but again ultimately we now have the data to pair that trial.
And we'll make sure we do so and then we'll confirm that we've maintained a the power we desire there with an interim analysis when we do run that trial.
Right. So I am I thinking my phone cut out there for a minute, but that'll make sense to me and I guess just one maybe a quick question would be you know what was the rationale for.
Increasing the size of the atopic dermatitis trial.
Yeah again that was based on maintain and you know a high level of power to see a statistical difference and when we started that trial, we really didn't have any oral cursive a data with provide us endpoints and of course as we've just discussed we know and we did at the end of last year.
You know.
To achieve the primary endpoint for or because of unsecured D.A.P. patients and and would that data in hand, we could model you know based on some assumptions related to placebo rates up hiring analysis and based on that we decided it made sense to increase the sample size just to make sure we had the appropriate parent.
Again with the increase sample size. We also incorporated an interim conditional power analysis just to make sure.
We were on track again, so that's really tuniu adaptations for a D and that trial is recruiting very well and we do expect to to complete the interim analysis next quarter.
Okay.
Well I have some more questions, but I'll hop back in the queue to give other people a chance I appreciate it. Thank you.
Thank you Chris.
Yeah.
Our next question comes from a line of David Amsellem.
Thanks, So so Derek you may have a a dress this but I wanted so just drill down in more detail can you talk about the phase three for oral consumer and CKD and the context of backgrounds medications.
What are your thoughts on which background medications that be part of the inclusion criteria, which would be excluded and what did you learn from the phase two study regarding use of background medications. That's number one and then number two is just a bigger.
Picture question City, except that you do a positive data in a topic dermatitis, Oh, that's obviously a different call point different.
Physician vertical if you will and is that something that you would plow ahead with interface to you on their own or is that something that you would you'd look to partner and I guess the broader question is beyond CKD you know what would you look to commercialize on your own and what would you look to partner. Thanks.
Thanks, David So on the first question we have looked at I think we mentioned that's before we did look at the background Madsen or phase two trial for for the you know pre dialysis CKD patients in the was some difference there between between those patients and what we'd seen and hemo dialysis patients so a higher percentage of patient.
Using you know centrally action drugs, such as gabapentin or or Pregabalin that doesn't seem to have heavily skewed our data however, but going forward. We were off the mind. The if we can eliminate these variables relatively easily and it doesn't enter.
So with a recruitment than we would.
You know most likely we may lead patients with around TST means which is a relatively small percentage and not patient population.
Because that tends to help them sleep, but it's most likely we try to eliminate as much as possible and the phase three design. So that's what we did there in terms of you topic down yes, that's a that's a different co point than that so there's a large population of course also.
So ultimately from a commercial standpoint, you know I think we were perfectly capable of running a late stage.
Trial in the atopic dermatitis, you know we spent some time recruiting.
You know experienced a development personnel into the company. So that we can we can handle that beyond the registration level trial, it's true that that would require some effort commercially and it's most likely at that point.
We'd look to partner that particular that particular indication with a with a larger partner, but you know running late stage trials is basically what we are designed to do here as you know David and I think we could do we could easily I comedy a late stage trial and the topic Don.
Okay, and I would imagine there that the logic would be applied to a liver disease setting as well as you run the late stage. So study, but you know may explore partnership there.
Yes, yes, I'm just to reiterate and I think you and I have had thus discussion I think on this call. Previously you are our strategy here in terms of ultimate label for the for the oral formulation of cursive as of course, a broad one and strategy.
We're following as you know there if you like various pathophysiology that lead to provide us and they have definitive in separate if you like pathophysiology is and we're looking to see activity and these different patient populations as evidenced if you like ultimately that this is.
A mechanism and we talked about the mechanism earlier that should a broad applicability and so it's unlikely we'd run registration programs and every patient population. We're looking out here you know we will <unk>, we will be selective on on the first patient populations, we take forward, but ultimately all the best did I was going to be useful.
When we have that discussion related to getting a broader label.
Moderate to severe right [noise].
That's great. Thank you.
Thanks, David.
Thank you.
Our next question comes from the line Annabel.
So many with Stifel. Your line is open.
Hi.
For taking my questions.
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Okay.
So.
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Okay.
Yes.
At this point.
A number of physicians are consultants.
Yes.
Yes.
Uh huh.
And if you're not going to see as much.
Response.
And second.
The trial.
Assumptions.
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Idmc.
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Based on their specific calculations.
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First question.
Yeah, not as great question, and so on a de population in terms of looking at placebo you know there's a lot of data there as you know from a lot of different drug classes look in a.
Particularly.
Disease alterations in terms of endpoint, but also looking at Pruritis and so there's there's a lot of available information. So when we when we look at that and key late that and look at the the normal placebo rates, we see and then we look to the variability we had within our CK D.A.P. oral trial.
That those would really the two factors we thought about in terms of looking at what would be the sample size to maintain you know hi, a statistical power to see a specific treatment effect.
And that's how we modeled that so was modeled based on if you like historical placebo race I had been seen in the topic population as well as the treatment effects, we'd seen with with oral and just trying to extend the variability we'd seen there. So that was the idea of opening the sample size to accommodate the possibility of an increased placebo response essential.
<unk> and again, you're right with we've introduced in the interim conditional power assessment, we can actually if you like confirm those assumptions when we have 50% of a patients complete.
And again you are correct based on the Idmc recommendation. We can then altered that sample size to make sure. We're going to maintain you know a conservative power level to see a statistical difference would also interested in this particular trial and not only looking at me none or as change. We're also going to be looking at responder analysis with that so so that.
It was really the whole rationale we had kind of historical data versus.
Are you if you like in conjunction with data we generated with oral cursive that was the basis of upsizing that.
Sample size there for a topic.
And if I understand correctly.
So for sure.
That's gotten a secondary.
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I wouldn't say, we are not well, where that's our butts. Our aim is to maintain sufficient power to see a response and I'm not secondary endpoint as well and again not again, we'll have some advice on not from the Idmc as you point out when we have the analysis that 50% of the patients completing the treatment period.
Okay.
Just curious about the PBC.
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So.
Yeah.
Well you're not us.
Again, Lucy I think we've discussed as before and that's a that we truly see as a proof of concept trial for for liver disease. As you know PBC is an orphan indication that is quite difficult to recruit not patient population were in fact, expanding beyond the U.S. and UK at this point to gather more more patients for that so.
So there are we you know we want to make sure we get enough patients to see.
Our signal, but that's a much more challenging populations and that gets back to the discussion I had with David. The you know we hope to see data there that is gonna be supportive ultimately of getting a broader label for oral cursive <unk> and and provides.
Great. Thank you.
Thanks Annabel.
Thank you.
Our next question comes from Milan, Jason Gerberry with Bank of America.
<unk>.
Hi, Good afternoon. Good evening, everyone thought this is she on for Jason.
First question.
Picky back here earlier question about alignment.
Yeah.
To meeting.
Or CKD just curious Derek.
You know given the.
There are.
405000 patients have exposure to the I'd formulation of CKD.
He is a thoughts on whether there could be potentially additional conversation with the beyond the alignment of whether that could be a smaller trials.
Three or maybe a smaller safety database given you already have a wealthy amount of safety database from the already and I have a falloff that that thank you.
Yeah. Thanks, cheap, yes, I think I think Weve also discuss the discuss that possibility previously here and that has been our thought for for oral CK D.. We do have a as you point out several thousand patient exposures with Ivy cursive.
In CKD, if you like end stage patients actually at a higher exposure level than that we obtained with our with our oral tablet formulation. So we do think it's a reasonable case that we should be able to reference those safety exposures as part of our phase three program for for oil.
CKD and pre dialysis patients of course, ultimately that's a decision for the F.D., but I think is reasonable that we could propose that as a as a path forward there aren't perhaps as an upside as you indicated that may result in.
I read this number of a registration trials for that particular program again, we can guarantee that something is something we thought about and something we will investigate when we have our ft interactions.
Got it and maybe if I can clarify on the expanding trial was tied to the trial numbers pretty I'm sorry, the subjects had 40 80.
When you said you I'm modeling base on the historical 80 response rate based on thinking about data and so.
At the effect that you see and Oh CKD Ida CKD trial are you taking into account that placebo response on the CKD or not I wasn't sure about that so I just want to.
From that that is a factor on weather.
Factor into the colleagues.
Increase thank you.
Yeah. Thanks, you you know we're looking at the treatment effect, we achieved with Sicad de Oro.
But predominantly we're looking at.
Historical placebo rates and the topic population, we realize these are completely different patient populations and it's much more likely the it de patients have had there.
Condition for much much longer than early stage C.J.D.. So we do expect.
Different placebo response rates from a de than we see in CKD, but what the benefit.
Of the treatment effect, we'd seen with oral that's something we can incorporate into those models and not again in combination with what we expect and the depopulation was the basis for for increasing the sample size there.
Got it and maybe if I kind of quick fall off if you can't provide any incremental color or guidance on how we should think about.
Yeah versus last year. Thank you.
Yes, well as as Rick pointed out overall, we do expect our cash position to carry us through this year and into the second half of 2021 in us obviously executing and all the programs.
We've been discussing the quarterly born as you know, we don't guide from quarter to quarter, it's gonna be a little lumpy through this year and Rick do you want to identify and stuff I think with a higher level trial activity would be expected that will be higher in 2020 than it was in 2019.
As we aren't as we complete our phase three trials Ci and then and then file the N D and the second half the year.
Awesome. Thank you so much.
Thanks you.
Q.
Our next question comes from the line of Charles Duncan with Cantor Fitzgerald.
Yeah.
Hi, This is a piece of proposals on for Charles Congratulations on 29 feet.
So.
For sure.
He probably dermatitis study.
Are you, including or excluding any patients on a particular medication or refractory to any particular medication.
Well Matt.
Well, Hi, P., Yes, we are Washington patients have all their medication, so they're gonna come clean on to that trial no no medications.
Okay and.
Yes, Tom to study.
When you increase the.
The other sample size for north to maintain statistical significance.
Is there any particular geography revenue patients from.
Disburse centers.
Well you know when we increase the south is a bad personally a 20% increase in sample size. There most of those patients since I'd almost all of those patients came from U.S. sites, the additional 20% an overall.
Last majority of patients can come to our indeed from U.S. clinical sites.
Okay, and how many of the clinical sites actually overlap between the first study in the second study.
Virtually none so those were separate sites a income to then from from kind of one.
Alright. Thanks.
Congratulations on board.
Thanks Pete.
Thank you next question comes from the line of Alan Carr Needham and company your line.
Hi, This is Joe on for Alan Thanks.
A quick one on the upcoming.
Results. These two.
Well, maybe you can help us frame expectations potentially around maybe.
Maybe response rates or improvements.
And.
Number of oral and some.
Out there, but in terms of phase two comparison, what would be one or two in your view as best competitors.
Yeah, Thanks to a I mean, it you know as it's hard to come up with a can pardot because as you know we are really the only company that is investigating that's modality, there's not a lot of.
You know prior data.
Using this approach other them with you know nonselective, if you like medications that are being used there so.
You know there is a standard the F.D.A. likes for dorm conditions.
And that's a four point responder analysis and that's that's what we're looking as our mean secondary analysis here again. The reason we have used mean in our asked as a primary and have done so consistently in all our phase twos as that continues variable is much more sensitive to identify an appropriate dose and as you know as it.
It was range and trial, but we will.
We look you're not the the four point responder allowances and again that was one of the reasons that we adjusted sample size and not trial.
Great. Thanks.
Hi, sorry.
Thank you.
Next question comes from the line Arlinda Lee with Canaccord. Your line is open.
Hi, guys, it's Ben Shim for Arlinda.
My questions have been answered and I'd, just like to maybe ask one thing as we get closer.
Data and then to ultimately filing for the IB Pruritis.
Maybe you could you provide us a little bit more detail on the cadence and magnitude of.
Coming milestones that you may potentially earn from by for this year.
And we will they be accounted for in any special way or are they going to be just straight revenue. Thanks.
Great. Thanks, Ben I, you know I did in terms of milestones with V for specifically I think we've we've guided before on the total woman there and divided that in terms of regulatory and commercial so there is $30 million and regulatory milestones that will be coming to us via.
Without via that particular arrangement, we haven't actually get it does to particular quarter, we expect to see these ben but that's the level of milestones.
That is part of that license agreement beyond the there's another 430 mile 430 million in commercial milestones for sales at with the U.S., but as we go forward and we filed the N.D.A.M., we have more visibility on the timeline for launch and approval.
Then we will guide as to when we expect those milestones, but again to reiterate and Rick said that all the guidance. We've given in terms of financial one runway here is excluding any projected milestones from before fuzzy answer R&D, maruishi or or CKD pharma.
Okay, great well congrats on another great year and keep up a good work. Good luck to you great. Thanks. Thanks Ben.
Thank you.
Your next question comes from a lot of after hall with Janney. Your line is open.
Hi, I got two questions for the first one regarding interest statistical analysis.
Next quarter or atopic dermatitis, what's the range lower upfront.
Increasing sample size, it's required and then Oh.
Yeah, Hi, aster. Thanks for that so so you know we haven't actually divested publicly yet the upper range of what we would increase the sample size to their you know one thing I can say is that we're going to look at that on a curve. So it will have an ability for the idmc to guy does.
Two specific patient number.
And also that will be directed towards if you like the most active dose that we see again. This is a dose ranging trial. So so that's what we're most interested done but we haven't actually get it as to what the upper limit that would be at that point.
Okay and then my follow up is so as we get closer to come to data potentially launch can you remind us of your launch strategy any additional details on how vifor fresenius and some roll out of course.
Well you initially focused on for Daniels clinics together lead that there's any has any detail. Thanks.
Yeah unfortunate I can't give you much detail on that that that's that's confidential at that point asked or we are of course working with before fresenius to coordinate that we have undertaken.
A whole range of activities and preparation for launch Precommercial activities really across across the company. We've established and we are expanding and MSL team here at Kara and we're working to broaden our cable L. universe increase awareness of CKD associated providers we've stopped.
Leashed regional National Advisory boards were sponsor in strategic education opportunities include and see a me symposia at the appropriate meetings and we're trying real hard to increase or cursive, a publication footprint not you're gonna see that throughout through at this year and then of course on our commercial side, we will be hiring.
You know some senior level people in sales and marketing.
Market access later in 2020, so there is an integrated cross functional plan in place to accommodate the launch and we're also coordinating as you indicate with before for Xenia, specifically in relation to our co promotion arrangement here in the U.S.
Thank you.
Thanks Esther.
Thank you.
Ladies and gentlemen that concludes our <unk> session.
I would now like to turn the call.
For closing remarks.
Thank you everybody for participating on the call today I'd also like to thank our hard working carrot team.
Our study investigators and all the patients who continue to participate in our clinical trials and we're very much looking forward to updating you real soon and throughout the year. So thank you very much I have a great night.
Ladies and gentlemen. This concludes today's call. Thank you again for your participation you may now disconnect everyone have a wonderful day.
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