Q2 2019 Earnings Call
All participants are now in listen only mode. There will be a question and answer session at the end.
Please be advised that this call is being recorded at cara's request.
I would now like to turn the call over to care team. Please proceed.
Good afternoon. This is gene or hang with Stern Investor Relations and welcome to Cara third Therapeutics second quarter 2019 financial results an update conference call.
The news release became available just after four o'clock PM today and can be found on our website at www Dot Cara Therapeutics Dot com.
You May also listen to a live webcast a 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 completion and announcement of the results of our ongoing clinical trials.
The expected timing and design of our planned clinical trials.
Future regulatory and development milestones for our product candidates the timing of regulatory submission the potential for CRD, four or five to be a therapeutic option in multiple practice syndication.
The size of the markets that are potentially addressable by our product candidates and our expected 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 insured therapeutics filings with the Securities and Exchange Commission, including the risk factor section of the company's annual report on Form 10-K for the year ended December 30, 120 team and its other documents subsequently filed with or furnished to the securities and Exchange Commission.
Participating on this call are Dr. Derek Chalmers.
Karen President and CEO , and Dr., Mani Mohindru, Chief Financial Officer, and Chief Strategy Officer, I'll now turn the call over to Dr. Chalmers.
Thanks, Jay and good afternoon, everybody and thanks for joining us on today's call.
So we've continued to make very significant progress during the second quarter of 2019, particularly with our lead cursive injection development program.
Well, we reported positive top line data from our first pivotal phase three trial.
One and hemo dialysis patients with chronic kidney disease associated private source he can't D.A.P.
We are very pleased to see the treatment resulted in statistically significant improvements in all primary and secondary endpoints in this trial.
And we remain on track to read that topline data from our second pivotal phase three come to trial.
And the same patient population and the fourth quarter of this year.
In addition to the Cam one data and their ongoing come to trial. We're also making good progress in advancing the development of oral courses across a number of patient populations, where providers continues to be a significant unmet need.
We recently announced the completion of enrollment in our phase two trial of oral Chris is that for CKD, a pea in stage three to five CKD patients and we remain on track to report the top line data from this trial in the fourth quarter of last year.
We've also initiated two additional phase two trials with the CKD population the first in patients with chronic liver disease.
Specifically primary biliary cholangitis patients suffering from providers and the second in patients where they topic dermatitis.
So with a recently completed successful follow on offering which netted approximately a $136 million to the company, we remain well positioned to execute on our lead the pivotal phase three program for IB courses for CECO D. P. In hemodialysis patients as well as progress our oral cursive of programs across multiple patient population and the coming quarters.
So before we provide an overview on each of our ongoing programs I want to briefly remind you of cursive as mechanism of action and why we believe it has the potential to be a treatment of choice for providers across patient populations.
Sure server has been specifically designed to function without traditional new opioid side effects due to its highly specific pharmacological action on kappa receptors and lack of activity on year receptors.
Jewish unique chemistry that restricts it to the periphery cursive as mechanism of action is mediated by Kappa opioid receptor is specifically on progress for all sensory off fronts.
Which you relay provider signals not within the CNS.
As well since action on capital receptors on immune cells.
The action of courses on Dynamo and epidermal immune cells blocks the release of a range of nerve sensitizing molecules are pre religions.
Diminishing the stimulation of demo sensory fibers and we believe that is that's the deal Nagorno and anti inflammatory effect that affords cursive, an effective anti pruritic action, regardless of the initiating pathophysiology and the patient.
So moving on to our clinical programs, let's start with our lead program pursue the injection for hemodialysis patients with CKD IP as we've mentioned before on these calls. This is a patient population were approximately 40% to 50% of patients suffer from moderate to severe provide us.
Not only does provide a severely diminished patients quality of life in the form of sleep disturbance in depression anxiety, but it's also associated with increased morbidity and mortality in these patients.
Pruritis remains a significant unmet need here and these patients undergoing dialysis with no approved therapies either in the U.S. or in Europe .
Our pivotal program focuses on injection and hemo dialysis patients includes four phase three studies.
Tom one our U.S. efficacy trial come to a global efficacy trial and two open label safety studies, one U.S. and one global.
Both Cam wanting Cam two are designed to investigate the efficacy of course, if injection at a dose of <unk> 0.5 micrograms per kilo versus placebo.
Administered three times per week or T. W. After schedule dialysis sessions over a 12 week treatment period with a 52 week open label extension phase beyond that for safety.
In May we announced top line results from Cam one.
Analysis of the primary endpoint demonstrated that cursive injection significantly reduced etch intensity with 51% of subjects achieving at least a three point improvement and worst etch intensity as measured on a and R.S. or numeric rating scale compared to 29% of subjects in the placebo group.
That's for the secondary endpoints, 39% of subjects treated with cursive achieved at least a four point improvement.
And the worst etch intensity and our escort compared to 18%.
In the placebo group.
[noise] impact of itch on quality of life was obsessed with two complementary multi dimensional it's really the quality of life questionnaires, the five D H and the skin index Tan.
These questionnaires evaluated h. symptoms and its ability due to age including impact on sleep work social interactions and mood.
Notably patients so impressive experienced a 35% improvement in the average total five DXL store and a 43% improvement and the average total skin index 10 score compared to placebo at week 12, both of which were highly statistically significant improvements. So overall these data indicate a consistent continued onto poetic effect of coercive.
Over the three month treatment period, and this patient class.
We continue to make good progress on our second pivotal phase three trial come too, which is a global study similar in design to become one trial, that's with Cam one we have designed a pre specified interim conditional power assessment into the camp to protocol and we expect to announce the outcomes of that analysis and fill topline data from calm too.
Before the end of this year.
Moving on to our safety studies in this program are open label 52 week Safety study currently has approximately 165 patients through six months of treatment with over 50% of these patients having completed one year of course is a exposure.
To date, the safety and Tolerability appears to be consistent with data reported from the first phase three and prior phase two trials of cursive injection and hemo dialysis patients.
And based on the most recently completed independent data safety monitoring board to valuations the last of which was in July of this year no one knew or inconsistent safety signals have been observed.
Our second open label Safety study initiated in Q2. This year is utilizing both us and European sites and is expected to enroll up to 400 patients and as a reminder, this drop was not required by any of the regulatory agencies, but rather as part of our strategy to use new clinical sites to accelerate the safety exposures required for a potential and D.A. filing. So in summary, our pivotal program for cursive injection, then hemo dialysis patients with CKD T.A.P. is advancing on track.
Pending positive data from come to later this year, we are undertaking all necessary activities to support submission of the new drug application focuses on injection to the FDA and the second half of 2020.
And then anticipation of a successful Indiana potential pursuit of injection launch in the U.S.. We've also initiated a range of key pre commercial activities.
Including the recent completion of a commercial manufacturing agreement with Patheon UK limited.
Now moving on from cursive injection I like to turn to the other part of our pipeline.
Our ongoing programs with oral CRE server based on provide us related drug prescription data. It's estimated that there are at least 2.5 million stage three to five CKD patients suffering from providers and the U.S.
With current standard of care predominantly being generic corticosteroids and antihistamines.
Our ongoing phase two trial in this patient population is a multi center randomized double blind placebo controlled well week trial designed to evaluate the safety and efficacy of three tablet strengths of oral cursive <unk> 0.25, Megs 0.5, Megs and one Meg administered once daily and these patients.
The primary endpoint in this trial is the change from baseline in the weekly mean of the daily 24 hour West intensity and our score at week 12 of the treatment period and secondary endpoints include change from baseline and its related quality of life scores at the end of week 12 also again assessed by the total index 10, and five the edge skills and in addition, we're also assessing the proportion of patients achieving an improvement from baseline of greater than or equal to three points with respect to the weekly mean of the daily 24 hour work edging intensity score at week 12.
Based on the recommendation of the independent data monitoring monitoring committee or Idmc, We recently announced the trial will not require any modifications to the original enrollment target of 240 patients.
And that trial is now fully enrolled.
That's idmc recommendation was based on the results of the pre specified interim conditional power assessment that was conducted after approximately 50% of the 240 patients had completed the designated 12 week treatment period.
We remain on track to announce top line data from this trial before year end.
We also recently initiated phase two trials for the treatment of provide us and two additional patient populations, you topic dermatitis or read D patients and patients with primary biliary cholangitis or PBC patients.
The topic dermatitis is of course, one of the most common chronic inflammatory diseases with prevalence rates of up to 5%.
And U.S. adults and approximately 25% in children.
And provide us as a defining symptom of a D with a point prevalence estimated that 87% to 100% in that patient population.
In a similar fashion to CK D.A.P. current treatments for provide us across the 80 patient spectrum fall short consisting of topical corticosteroids.
Hi, there was antihistamines and antidepressants.
We recently initiated randomized double blind placebo controlled phase two study designed to evaluate the efficacy and safety of oral consumer for the treatment of moderate to severe provide us an approximately 240 patients where they topic dermatitis.
Subjects will be randomized to three tablet strengths of oral CRE Suva 0.25, Megs 0.5, and one make taken twice daily versus placebo for 12 weeks.
Followed by a four week active extension phase.
The primary efficacy endpoint is the change from baseline the weekly mean of the daily 20, 424 hour H. and R.S. at week 12 of the treatment period and secondary endpoints include change from baseline in etch related quality of life scores at the end of week 12 as assessed again by scan index 10, and five D. H skills. We're also looking at the proportion of patients achieving an improvement from baseline of at least four points with respect to the weekly mean of the daily 24 hour.
And our score at week 12.
With respect to chronic liver disease associated providers. We also recently initiated a phase two trial in patients with a patrick impairment due to PBC.
Right. This is a common symptom of cost I think liver diseases with a prevalence of up to 70% and patients with PBC.
This phase two multi center randomized double blind placebo controlled 16 week trial is designed to evaluate the safety and efficacy of a one make tablet of oral consumer taken twice daily versus placebo in approximately 60 patients with PBC.
In moderate to severe provide us.
Primary efficacy endpoint change from baseline the weekly mean of the den Daily 24, our worst itch Anoro score at week 16.
And secondary endpoints again include change from baseline in H. related quality of life scores at the end of week 16, again assessed using scan index 10, and five D H scales.
As well as the assessment of proportion of patients achieving an improvement from baseline of at least three points with respect to the weekly mean of the daily 24 hour West and Texas at worst intensity score at week 16.
So we will provide an update on enrollment rates and projected data readout timelines from both these initiated all cursive a phase two trials.
As we initiate more clinical sites and as we get a better handle of enrollment rates across both these trials.
So with that I'd now like to turn the call over to money, who will discuss our financial results for the quarter money.
Thank you Derek.
As a reminder.
The full financial results for the second quarter of 29 team can be found in the press release issued today after the market closed.
Second quarter of 2019.
We reported a net loss of 23 million or 58 cents per basic and diluted share.
Compared to a net loss of 17.2 million or 52 cents per basic and diluted share for the same period of 2018.
For the second quarter of 2019.
We recognized revenue of 5.2 million related to the vivo Fresenius collaboration agreement compared to 2.9 million.
For the same period of 2018.
For the second quarter of this year.
We reported R&D expenses of 24.4 million as compared to 7 million.
The fourth quarter of 2018, sorry off the second quarter of 2018.
The higher R&D expenses in 2019 were primarily related to an increase in clinical trial costs as well as increases in stock based compensation expense and payroll and related costs.
Gee any expenses the 5 million during the second quarter of 2019 compared to 3.7 million in the same period up 2018.
The increase in 2019 was primarily due to increases in stock based compensation expense payroll and related cost as well as franchise taxes.
Other income was $947000 for the second quarter of 2019 versus $467000 for the same period in 2018.
The increase in 2019 was due to an increase in interest income.
Resulting from a higher average balance of a portfolio of investments in the 2019 period.
At June 30, it 2019, our cash cash equivalents and marketable securities.
Total 135.6 million compared to 182.8 million at December 31st 2018.
The decrease in the balance of cash cash equivalents.
With primarily related.
Type was primarily resulted from cash used in operations of 52.4 million.
That was partially offset by proceeds of 4.2 million from the exercise of stock options.
Additionally in July of 2019, we raised approximately 136.4 million in net proceeds from a public offering of approximately 6.3 million shares of our common stock.
Now turning on to our financial expectations.
Based on the projected cost of a clinical development and subsequent to plan as well as the timing expectations.
We expect that that parents cash cash equivalents and marketable securities as of June Thirtyth 2019.
As well as the hundred and 36.4 million from my July offering.
Will be sufficient to fund our operations into the second half of 2021.
Without taking into account any potential milestone payments under our existing collaboration.
I'll now turn the call back over to the operator for the Q and a session operator.
Thank you ladies and gentlemen, if you have a question at this time please.
All right then the number one key on your Touchtone telephone.
If your question has been answered.
Move yourself on the queue. Please press the pound key.
Again, that's star then one to ask a question.
To prevent any background noise, we ask that you. Please.
What's your question has been stated.
Our first question comes from Chris Howerton with Jefferies. Your line is now open.
Hi, guys. This is saeed in for Chris today, Thanks for taking the questions. Just wanted to start off by asking if you had any updates in terms of when you could expect to file an anda for IB course uba.
Yeah I see thanks for you yeah, as we said.
On the call on the summary of the creative injection program based on the project degree does some of the ongoing clinical trials, we would expect them to file the Andy in the second half of 2020.
Got you sorry, I must have missed that I'm sorry.
Okay. The the next question that I had was related to your discussions with CMS on today, but are there are there any updates there.
Well I guess, the only update as you probably know that they've released their.
Annual.
For post the update to that rule.
Which is essentially neutral.
For Kara, we're going to retain our two dapa eligibility.
Because we had a category one and D. and we will be a category, one and da which isn't and da with a new molecular entities. So.
As far as we can tell from what you propose the knot.
Rule, making up the it's essentially neutral for US one interesting aspect is that the debt extend that to adopt the period for Ivy perceive of which as you know is the first.
The first drug product to enter the to Dapa status from two years to three years.
Which was interest and to provide a longer assessment period for usage there.
But other than that we didnt CNS and that was.
It was a different for us in terms of our status within the legislation and as you know and we've said repeatedly we continued to interact with CMS they've been very positive faster.
Solving the issue of post to Dapa reimbursement for innovation and innovative products and and the interaction continues and we will certainly update everyone. When we see a result of the interaction.
Okay, perfect that's great to hear that on that timeline actually increased.
So thank you for the color there and then kind of like you know piggybacking off of that when you think about oral course through the it's not really subject to the to dapper risks three years from now how are you thinking about the opportunity for oral course, Eva in hemo dialysis patients.
Yeah. So at this point, we would direct an oral consumer towards pre dialysis patients as you know you know this is significant.
Unmet clinical need there was some 30% is the estimate from multiple sources, 30% of that patient population suffering from provide us with with no effective treatments. So that's the first patient class, we're pursuing with oral cursive. The Ivy form is really ideal for the hemo dialysis population, whereas you know that's a population that is heavily overboard and in terms of drug administration and a drug usage and so we can administer that compound three times a week after each dialysis session. So it's really an ideal dozing regimen for the hemo dialysis patients. So were specifically targeting hemo dialysis patients with Tresiba injection, and then pre dialysis patients and as you know beyond CKD patients into these other patient populations with oral consumer would be ultimate aim here that we see.
Really a broad label potential for oral cursive, regardless of the initiating pathophysiology as I've said across these patient populations.
We believe based on the mechanism of action that could be a broadly applicable drug. So so that's the differentiation there between tresiba injection and all.
Thank you.
Again, good luck on the progress and I'll hop back in the queue.
Thanks Syed.
Thank you and our next question comes from Jason Gerberry with Bank of America. Your line is now open.
Hi, good afternoon, thanks for taking my questions.
Just a couple from me first just coming back on that.
Yeah.
You think it's fair to say that.
Interactions.
Are being held back and so you have two positive studies in hand.
War or do you think.
CMS may want to wait until we're getting closer to the end of <unk>.
Period for more substantive discussions and dialogue and actions.
There.
Hi, Jason.
I don't think so you know.
You know as a government organizations I take your point and cynicism related to.
Actually before necessity, but you know.
When we look at the precedent, there, which is ivy per se, but from I'm I'm Jan They certainly knew they had to drop us a status actually a round about the N.D.A. point when that was up for approval.
And then they got advice on expansion as you know well ahead of the limitation on that so.
You may be correct said, there was going to look for a little more certainty on the N.D.A., but that's rapidly approaching for us and as I've said our interactions there have been.
Very positive at multiple levels and we really have a we have a good relationship with CMS, there well well aware of the differentiation between this product which has.
Breakthrough status for an unmet need in that patient population.
And for example, other me two drugs that may address anemia, or some other aspect of of the dialysis conditions. So they are actively engaged with us and exploring mechanisms that can differentiate and encourage innovation.
This is what's out there. So you may be correct that there may be a timing issue related to development, but as I said, we're rapidly approaching and D.
Coming up next year, and so we would expect to see some movement from them certainly once we have our NDN submission or not for approval.
Got it.
And then my second question just for oral oral pursuit, but just thinking about the development pathway.
Assuming that the phase two trial is successful can you talk a little bit about sort of the number of patients you need to dose at your therapeutic dose level could the phase two potentially count as a pivotal trial.
You too to totally wrong, a single follow on phase three pivotal trial.
I guess the market just wondering sort of how those variables shakeout.
Yeah No. That's a good question. We had we had thought the same thing Jason the argument being the if you're looking at CKD stage three to five versus hemo dialysis. It's essentially the same mechanism in same disease process and therefore, we would argue that safety exposure is achieved with preserved injection really at a higher exposure level should be relevant for oral cursive a development taking your point.
And there, we probably make the argument with cursive injection and the approved that this would be a candidate for an S.N.D.A.
And you're right that would be one.
A pivotal phase three trial. So yes that has been our thought that we've run the trial as you know the phase two trial with a 12 week treatment period, which would be.
A requirement for supporting.
Efficacy trial, so ultimately we will explore that avenue.
And that's a possibility we're not going to count on it but it's a possibility.
Got it and then my last question just in terms of the phase two.
Chronic liver disease trial, just in terms of the.
You know slightly smaller number of patients per arm versus some of the other phase two trials that you've run.
Oh, they're different powering assumption with respect to this patient population and this study.
These studies just curious if you can comment on that.
Yes, so really the issue there as I was you know PBC is not a gigantic patient population.
And so we but we did choose a deliberately because of the range of liver diseases associated with severe providers those patients tend to have the most consistent provide us issue and and so that's hopefully so the ideal for a proof of concept trial. So we really view that trial is a proof of concept.
I'm looking at effect, a drug effect within the patient class and then after that we'd probably defined that more in terms of dosage. So we've chosen to dosage, there which is a little higher.
The top of the range, we'd used for for other indications, where we know we have very good exposure, we have run a phase one trial.
And there was a chronic liver disease patients. So the idea there is really to look at proof of concept and then after that we may look at appropriate dosage beyond that particular trial.
Got it thank you very much.
Thanks, Jason.
Thank you and our next question comes from David Amsellem with Piper Jaffray. Your line is now open.
Thanks.
You touched on it earlier.
The broad.
Underlying.
I guess the question here and maybe it's tough to answer.
Might be a little early to do so.
What do you think.
Tipping point.
Well you can get there.
And have you had any communications with the FDA.
In terms of.
Our friend.
Diseases that they want to see before.
Comfortable.
Kind of indications.
More broadly about.
For instance.
Yes, well results.
That's it for me.
Im setting.
Thanks right.
Thanks, David both both very good.
Questions and things, we've we've obviously considered so on the first on the broad label.
I wish I could tell you the F.D.A. Dumb Division had issued a set of guidance on on a clinical populations to look out to achieve a broad label when they're not quite there yet. So so we're working our way through the patient populations pair IC age to begin with and as.
As Jason was probably not we <unk>.
And the last question, we may indeed have a specific advantage to get up to get a fairly rapid label with CKD at this point since we have such a large level of exposure there and the hemo dialysis population so that makes sense as an initiating.
Patient population, but I will tell you our thoughts on that's not necessarily I should.
I should point out not not necessarily the F.D. his thoughts on that but where we would look to the us and our logic on that says you know there are various if you like path of <unk> pathophysiology is associated with provide US is obviously dermatological, whereas you point out where.
Were nine barking on our topic dermatological a trial the end organ disease associated provide us if you like and there's neuropathic or provide us that's the major three groups. So so so there's also some smaller populations associated with psychogenic.
Right is there a thought says if we could sample that this would be analogous to a broad pain label, whereas you know the division looks for examples of efficacy across pain types neuropathic inflammatory and so on I thought as if we can show efficacy across these various categories of provided US then that would be the case that this would be a mechanism that should ER should achieve a broad label again those are our thoughts and thus our rationale for how we move forward not per guidance of the F.D. I want to emphasize but that's how we're thinking about this as we embark on each of these.
Patient populations and then your second question on a D., we do think a D.
Is the most appropriate population here for a couple of reasons first of all very large unmet need for for anti predicts there and really is a population where the current therapies for providers are really again. These older generic corticosteroid Sandiest mean, some high dose.
Antidepressants and it's also an area where biologics are really only focused on the moderate to severe subgroup within not patient class and as you know that's a minority that patient class about 80% of the depopulation as mild to moderate weather really isn't a biological.
ER approval. They are so we think there's a very large.
Opportunity and an unmet need for an orally available onto prophetic versus psoriasis.
Where we feel and again this is advice Weve also received from our former K wells in this area, but that's an area pretty well served by a range of biologics, which are quite effective.
And not mechanism there. So so our belief is we focused on the right group so not to say that that's mechanism wouldn't be effective and sorry, I think you really did provide us most likely so we haven't run it.
And ultimately there might be an opportunity there to my view that as a first line therapy.
You know.
What's the biologic is as you know we have no metabolic issues with us molecule either so there's no D.I. issues whatsoever, so but again, we focused on what we think is a big opportunity here with his last.
If you like availability of effect of biologics.
Okay. That's helpful. Thanks again.
Thanks, David.
Thank you and our next question comes from Annabel Samimy with Stifel.
Your line is now open.
Good afternoon, everyone. This is Nick.
On for Annabel, Thanks for taking our questions.
We've been discussing the opportunity is for anti Pruritic drugs for security and.
The number of physicians and without a doubt they all see the significant need the caveat being that these patients are extremely sick in treating them with systemic Asians.
Usually difficult with the drugs are taking.
So we know the IB courses has been relatively clean, but those patients get dialysis to clear. The drugs. The question is will require you to conduct any different studies or drug interaction studies for the oral form with the typical drug scene in CKD are sealed.
Yeah no. Thanks, Nick that's that's a good question and again I can I've touched on us and the answer to Davids question well you recall, what we've got here with cursive as a pretty unique chemistry, it's not a standard organic head to cycle and in fact, it's a de amino acid tetra peptides. So its not metabolized through the lever at all.
Not a substrate for any set enzymes, nor does it and have it already say any of those enzymes. So we've actually Ron I'm, a very exhaustive di di I panel based on standards F.D.A. guidance, there and I can tell you with some confidence that those that's molecule does not have great potential for drug drug interaction based on the standard panels. We've looked out there. So you know we have run less than you were correct, particularly in the CKD population that are heavily burdened with co medications and you've probably heard us.
Discuss that's another calls that we really don't limit up for these patients when we run our trials in fact, we even a lot of these patients to come into the trial with their so called standard onto predicts which are mostly antihistamines.
And Weve had no issues whatsoever. There. So the drug is very clean so the drugs really really clean by by virtue of its metabolic profile.
Other than the fact that its dialyzers.
Every three days from these patients I know you haven't seen the data that yeah, but you're going to see based on our blinded data and I think I've said on previous calls we have are independent safety monitoring board look at our oral safety as well as their Ivy and.
And we're seeing no differences there so I think you're going to see that does there's a good safety profile for the molecule across patient populations and across the formulations.
Awesome. Thank you and I guess also.
Just notice in the field.
The population or study you have the one dose two times versus three doses or three times daily for.
The we just want to know the rationale.
Between the choices humid between those two studies.
Yeah as I said earlier I think it was Jason It was argue and we really see the lever started as a proof of concept or not patient population. So we went to the hot the upper range of our tablet strengths there really to get proof of concept gets signal there and then we'll we'll look at proper dose range in that group and the reason we dosed twice a day is the they don't have for the most part any inhibition and kidney function as I said, we run our phase one in that trial and we know dosing twice a day is appropriate for that patient population.
For I picked you up directly I think you're trying to save for CKD. We do is that once a day and the reason for that as the drugs eliminated.
Essentially whole via the kidney Sirona CKD patient and they have a very long a beta phase extension a excretion phase on their P.J.. So they really only require once a day dosing versus a liver patient with the kidney function as normal and they take twice a day.
Okay, great. Thank you.
Thank you.
Thank you.
And our next question comes from Charles Duncan with Cantor Fitzgerald. Your line is now open.
Thank you.
Good afternoon, Derek and team congrats on the progress in the quarter.
And thanks for taking the question had a quick one regarding come to wanted to.
I ask you about timing and sizing obviously column one was a huge success.
Notable data crossed all endpoints, but I'm wondering given that result would you would you imagine that there could be a I'll call. It increased expectations for could resulting colm to EM might you consider that in terms of the size of the trial.
Especially given the upcoming interim analysis.
Yeah. Thanks, Charles Yeah, you're right, we were and I think I said in our prepared remarks, we were very pleased with the data from Cam one where we we sell very robust response across endpoints. So.
You know I think that feeds into our confidence that we modeled this correctly in terms of hiring which as you know it was based on our on our phase two.
Cursive, a data and and hemo dialysis patient so.
So you know my lawyers wouldn't let me be overconfident, and projecting and predicting how great. Our cam two data is going to be so we're going to wait and look at the interim analysis, but you know we have high hopes.
The interim analysis.
Will reflect what we think should be adequate power for for Sina Statistical difference there, but we're going to look at the data and that's coming up in the next couple of months and we're going to see the data readout.
By the end of the year on that trial, so yes, you're correct Cam one was.
Confidence boosting in terms of where we see cam too, but at this point, we're going to.
We're going to follow the data on user interim assessment and make sure. We got the power assessment correctly and again I think.
You and others have pointed this out in the past that with global trials, there can be differences in terms of variability.
Versus U.S. trials and again just to reassure you here, we do designate cam to as a global trial, but.
You know approximately 50% of the sites in that trial also U.S.. So we're fairly confident that should be.
Reflective of the kind of standard deviations, which in turn can one but again, we're going to make sure of it and we're going to run a interim conditional power assessment, we're certainly going to advise us to the outcome of that.
When we have that completed yet.
Super that make sense to me also second question was regarding go to market strategy.
I think you mentioned some pre commercial activities that you plan to engage in a over the course of next year. What are some of those go to market or a pre commercial.
Endeavors that you'll be pursuing beyond manufacturing would you be looking to hire some you know.
Sales type people or anything like that and what would you anticipate the burn to be over the course, the or or spend for that endeavor.
Yeah. Thanks, Charles <unk>, Let me answer the last part of your question first in terms of sales and ultimate sales force, that's not something we're going to.
We're going to hire in the next year, that's really going to be ultimately dependent on N.D. approval. So the majority of the expenditure related to what we projected doesn't necessary sales force for for this cursive injection.
Product, which we've said before is is relatively modest to serve the dialysis population somewhere around 65 to 70 sales reps were going to see the majority in fact, almost all of the expenditure is going to come after India approval. So what are we talking about in terms of pre commercial activities right now our standard.
MSL teams are being assembled in fact, we have.
You have that hiring under way, we're going to embark on education related to the condition that self Boston both in terms of P.I. education and patient engagement related to that we're engaged in appropriate AD com boards related to seek a D.A.P. in hemo dialysis patients.
Both locally and nationally and in fact internationally with our European partner before Fresenius. So those are the types of activities that we actually already have under way.
And obviously, making sure that we.
Develop the appropriate infrastructure here internally at Cara as we convert from a.
What I like to call a company on burdened by revenue.
A company that will move towards the revenue based.
Biopharmaceutical company. So all of that is underway all of that is gonna be staged based on success, So and I can see and money sitting beside me all of that was included in the in the budget from which we make our projections as to our runway.
After our last follow on offerings. So all of that said there are.
Bigger spend is not gonna come until we see.
Certainty on our India approval.
Sounds great then it'll be a good burden I have thanks for taking the questions.
Hi, its chaz.
Thank you and our next question comes from Alan Carr with Needham and company. Your line is now open.
Hi, Thanks for taking my questions.
Can you go over the in the client interactions you have with the FDA now that you've got the phase three com on data and then also can you comment on.
The timing of the NDA submission.
What pushes us to to reach 20.
Yeah. Thanks, Thanks, Alan So you know our interactions are really standard interactions forgetting an N D.
Submitted so we have you know internally began to assemble all the necessary modules that are going to be part of the.
And D.A. submission as we said before all of the preclinical work required here is essentially.
It's essentially done and that preparation is underway.
And we said also before in this call we have an upcoming meeting in the fall here with the F.D. and that's going to be really related to safety submission for the N.D. and absolutely defining and having certainty on the form on form of how we're gonna submit all of the safety data related to R. and D.A. will also be again as we said before on these calls we will also be investigating the composition.
In terms of the patient types that could be part of that safety exposure number and how we can get to that required number and again as we said before on this call. We've been implementing trials really related to <unk> guidelines here that are going to achieve.
The fiscal 1500 exposures, it's possible that we may get some so some sort of break on that as you know we have breakthrough designation.
With the compound so that's going to be the first interaction with the FDA, which is coming up in the fall and then next year and we're certainly going to advise as to when this happens there will be a standard pre N.D.A. meeting.
Well, we're going to run through all the necessary requirements to make sure we have everything in place to allow filing of that N.D. and then back to your timeline questions you know.
As you know and we've got I didn't we're confident we were projecting that we're going to have both kind of wanting cam two data available by the end of this year.
We're also projecting that the majority of our safety exposures are going to come.
Early next year and with those and Hot then we'll have a full package that allows submission.
Of the N.D.A. So that's the basis of the guideline that we see that's happening in the second half of 2020, if there's some sort of development with the FDA and we get some.
Recognition.
I've, a breakthrough status and the quality of our phase three data in terms of reduced safety exposures will certainly gate to that.
But we'll gauge and right now based on achieving this Phil I see ICH guidelines of the full quarter of safety exposures.
Just one last one do you have any plans to.
Presenter announce any interim data from the.
Those open label trials that you have running or.
Well, they really only see something after that completely done.
You talking about the open label safety trials Island, Yeah, Yeah, Yeah.
Yes.
Of course, you're going to see a amalgamated safety data both from Cam one income too and we you know we are in the process of submitting come one for publication to to peer reviewed medical journal and you're going to see that data hopefully relatively soon and Cam two will follow you you know ultimately I think with the amalgamated safety data that might be something we look to put out there, but that's not going to come in the near term that's going to be something once we have everything accumulated and together and something that's meaningful in terms of the population that we we want to summarize.
Great. Thanks for taking my question.
Thanks Alan.
Thank you and our next question comes from Esther Hong with Janney. Your line is now open.
Hi, Thanks for taking my question so on oral courses.
If the FDA agrees to a single pivotal phase three study in an S.N.D.A. filed where does that leave us in terms of a potential timeline could we see oral courses in the non hemodialysis patients launching within 12 months or shorter of the potential launch. Thanks, Yeah. Thanks faster I think it's just a little too early to think about the N.D.A. timeline until we get the first phase two.
But I do admire your enthusiasm to push this along we're equally excited by the old for server.
Potential. So so you know if we think about this realistically we're going to see our first phase two data.
I'm from CK. These stage three to five patients next quarter.
Before year end, we have guided.
And then if that's positive you are correct, we certainly want to talk to the F.D. about requirements for registration and that would occur in 2020.
Once we have that data accumulated and we certainly aim to initiate registration trials as quickly as we possibly could after the meeting.
So that would be the that would probably be as far as that one a project at this point and depending on the data and the receptivity to the idea.
We've just discussed in terms of S.N.D.A., then we could guide us to.
The timeline for NDS, but at this point, we're focused first phase two data and then hopefully with positive outcome, we'd look to an end of phase two.
As soon as we could in 2020.
Okay, great. Thank you.
Thanks Esther.
Thank you.
Good day, ladies and gentlemen, that's star then one to ask a question.
Our next question comes from Ireland with Canaccord. Your line is now open.
Hi, it's been calling in from under Thanks for taking my question.
I just had a quick question on.
He topic dermatitis can you give us a little bit more color on enrollment criteria what have your farewells advised on to her to exclude or include.
Yeah. Thanks, Ben Thanks for that question. So as I said earlier, we're actually looking at a whole range of <unk> D patient population. So we're looking at both mild to moderate.
Disease, if you like as well as moderate to severe.
So we're going to look at all.
Patient types, and then we're going to stratify them within the groups and the trial, but the main criteria for entry here is gonna be moderate to severe provide us so that's going to use this and.
That's going to be assessed in a run in period you have to qualify with moderate to severe and then they're entered into the trial, we're not gonna alive.
Any.
Background medication is going to be a wash out period.
For those patients, where we're going to remove all you know current.
Topicals are certainly systemic.
Medications, there's not gonna be allowed any rescue medication.
For the first four weeks of that trial and any use of.
Rescue medication that would lead to discontinuation.
After four weeks.
Care the P.I. judgment for the patient there, we could convert a patient to topical use and remain in the trial receiving.
Drug treatment, but that patient would then be qualified as a non responder. So so we have thought quite carefully about that population there'll be a washout period, no concurrent systemic or topical anti pruritic possibility of a rescue with a topical only any use of a rescue with the systemic which nullify that patient and they've moved to discontinuation.
Okay great.
Very helpful. Thanks, I know you've been spending most of your time talking to CMS said, you're engaged or at what point will you engage the commercial payers.
Yeah, again, I says with aster questions a little little early on that once we get our first efficacy data in phase two and we have a path to registration and we know what that path looks like that then that's the point, we start thinking about the engagement on the on the commercial side.
Okay, great. Thanks very much.
Thanks Ben.
Thank you.
I'm not showing any further questions at this time I would now like to turn the call back over to Derek Chalmers for any closing remarks.
Great. Thanks, you well. Thank you everybody for joining us on today's call I'd like to take this opportunity to quickly sank the caring team here in Stamford, Connecticut or study investigators and most importantly, the patients who participated in our trials, we would not be where we are today with your commitment and support and we look forward to updating everybody again soon so thank you very much everybody.
Ladies and gentlemen. This concludes today's call. Thank you again for your participation you may now disconnect have a great day.
[noise].
[noise].
[noise].
[noise].
[noise].
[noise].