Cara Therapeutics Inc (CARA) Q4 2018 Earnings Conference Call Transcript

Cara Therapeutics Inc (CARA 4.23%)
Q4 2018 Earnings Conference Call
March 12, 2019, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

See all our earnings call transcripts.

Prepared Remarks:

Operator

Good afternoon and welcome to Cara Therapeutics fourth quarter and full year 2018 financial results conference 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 the Cara team. Please proceed.

Jane Urheim -- Stern Investor Relations

Good afternoon. This is Jane Urheim with Stern Investor Relations and welcome to Cara Therapeutics fourth quarter and full year 2018 financial results and update conference call. The news release become available just after 4:00 p.m. today and can be found on our website at www.caratherapeutics.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 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 potential for CR845 to be a therapeutic option in multiple pruritus indications, the size of 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 in Cara Therapeutics' filings with the Securities and Exchange Commission, including the risk factors section of the company's annual report on Form 10-K for the year ended December 31, 2018 and its other documents subsequently filed with or furnished to the Securities and Exchange Commissioner.

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

Derek Chalmers -- Chief Executive Officer, President, and Director

Thank you, Jane and good afternoon, everybody. Thanks for joining us on the call today. 2018 was certainly a year of significant achievement for us here at Cara, including the advancement of our lead drug candidate KORSUVA across a range of clinical populations where pruritis is a significant unmet need, the signing of an important strategic licensing agreement with Vifor Fresenius, and the successful completion of a $92 million follow-on offering. So, this clinical and corporate progress has certainly laid the groundwork for what we believe will be a transformative year ahead for the company.

In 2018, we expanded our Phase 3 program of KORSUVA injection for chronic kidney disease-associated pruritis or CKD-aP in hemodialysis patients with the initiated of our two pivotal Phase 3 trials designated KALM-1 and KALM-2.

In January of this year, we announced we had completed enrollment of the KALM-1 trial and we remain on track to read out topline data from this trial in the second quarter of this year as well as topline data from KALM-2 in the second half of this year. Our ongoing Phase 2 trial of KORSUVA is enrolling pre-dialysis, Stage 3 to 5 CKD patients with moderate to severe pruritis with topline data expected here in the second half of 2019.

We also plan to initiate a Phase 2 trial of oral KORSUVA in patients with chronic liver disease associated pruritis or CLD-aP in the second quarter, following the recent completion of our Phase 1 pharmacokinetic and safety trial. And then lastly, we anticipate initiating a multi-dose proof of concept Phase 2 trial of oral KORSUVA in atopic dermatitis patients with moderate to severe pruritis around the middle of this year. So, overall, we're well-positioned to execute on our lead pivotal Phase 3 program for CKA-aP and HD patient as well as progress our oral KORSUVA patients across multiple patient populations in 2019.

So, on the call today, I'll provide more detail on each of these programs, but I'd like to first briefly remind you of KORSUVA's profile, which we believe underlies its potential to act as a broad anti-pruritic agent across clinical conditions.

KORSUVA is, of course, our novel first-in-class selective peripherally acting kappa opioid receptor agonist designed to function without traditional opioid side effects due to its highly specific pharmacological action on kappa receptors and its chemical structure.

KORSUVA's mechanism of action is mediated by kappa receptors on peripheral sensory afference as well as on certain immune cells. The action of KORSUVA on dermal and epidermal immune cells blocks the release of range of nerve-sensitizing molecules or pruritogens, diminishing the stimulation of dermal sensory fibers. We believe that this dual neuronal and anti-inflammatory effect affords KORSUVA an effect of anti-pruritic action regardless of the initiating pathophysiology, whether that's chronic kidney disease, chronic liver disease, or some sort of dermatological dysfunction.

So, I'd like to start with updates on our lead program of KORSUVA injection and hemodialysis patients with CKD-aP. As a brief reminder, the late-stage clinical program for KORSUVA injection in this patient population currently includes three ongoing Phase 3 studies, the KALM-1 study, a US efficacy trial, the KALM-2 trial, a global efficacy trial, and an open-label 52-week extension safety study.

We began enrolling patients in both KALM-1 and KALM-2 in 2018 and we recently announced both the completion of an interim statistical para-analysis and the achievement of full enrollment of KALM-1. Based on the recommendation of the Independent Data Monitoring Committee or IDMC, we did not adjust the sample size of this trial. The IDMC's recommendation was based on its review of the results of the pre-specified interim conditional para-assessment conducted after approximately 50% of the targeted patient numbers completed the 12-week treatment period.

To further clarify on this analysis, given the pre-specified decision rule and the formula used for calculated the conditional power, this outcome indicates that the results observed at the IA are consistent with the assumptions made regarding the sample size, to maintain desired power, to detect a difference between groups when we first planned the Phase 3 trial. Following the IDMC recommendation, we completed enrollment of approximately 350 patients in KALM-1 and we're on track to redirect topline data from this trial in the second quarter.

Our second pivotal trial, KALM-2 is also designed with a pre-specified interim assessment. Again, after approximately 50% of patients complete their treatment period and similarly to KALM-1, we look forward to providing the result of this analysis ahead of topline data, which is expected in the second half of 2019.

Both KALM-1 and KALM-2 are designed to investigate the efficacy of KORSUVA injection at a dose of 0.5 micrograms per kilo versus placebo. You'll recall administered three times per week after scheduled dialysis sessions over a 12-week treatment period. The primary efficacy endpoint is a proportion of patients achieving at least a 3-point improvement from baseline at week 12 with respect to the weekly mean of the daily worst itching intensity score as measured on a standard numeric rating scale or NRS.

Secondary endpoints in the trials measure aspects of itch-related quality of life. Using validated self-assessment scales, the Skindex-10 and the 5-D Itch, which we employed in our completed Phase 2B trial. Additional secondary endpoints include the proportion of patients achieving a greater than 4-point improvement from baseline in the weekly mean of the daily 24-hour worst itching scores at week 12.

The third ongoing Phase 3 trial in our pivotal program is an open-label 52-week extension study designed to evaluate the safety of KORSUVA injection on up to 240 patients. We now have close to full enrollment in this study with about 125 patients through six months of treatment at approximately 40% of these patients past the one-year exposure level.

To date, the safety and tolerability have been consistent with data reported in Phase 2 trials of KORSUVA injection and hemodialysis patients and based on a recently completed independent Data Safety Monitoring Board evaluation, no new safety signals have been observed in this study.

With topline data from both KALM-1 and KALM-2 expected this year, we remain on track toward our goal of developing KORSUVA injection as a breakthrough, first-in-class therapeutic for hemodialysis patients suffering from moderate to severe pruritis for which there are currently no FDA-approved treatments.

We also remain focused on advancing oral KORSUVA for pre-dialysis patients with moderate to severe CKD-aP. Based on generic pruritis-related script numbers, it is estimated there are approximately 2.5 million Stage 3 to 5 CKD patients suffering from pruritis in the US with current standard of care being predominately generic corticosteroids and antihistamines.

We're currently evaluating oral KORSUVA in an ongoing US Phase 2 trial of non-dialysis CKD-aP patients. This trial is a multi-center randomized double-blind placebo-controlled 12-week trial designed to evaluate the safety and efficacy of three doses of oral KORSUVA, a 0.25 mg tablet, 0.5 mg tablet, and a 1 mg tablet administered once daily.

From our Phase 1 trial of oral KORSUVA, we determined that these tablet strengths provided exposure levels in CKD patients with moderate to severe renal impairment, which were approximately equivalent to those achieved with the 0.5 microgram per kilo dose of KORSUVA injection in HD patients, a dose level which you know achieves statistically significant effects in both primary and secondary endpoints in our completed Phase 2B trial.

In this oral KORSUVA Phase 2 trial, we're expected to enroll 240 patients with 60 per arm. There's an unblinded interim para-assessment at 50% enrollment for those who have completed the 12 weeks of treatment. That allows the expansion of the study up to 480 patients. This trial is currently on track for patient enrollment and we look forward to providing with an update on the interim assessment in the coming months and ultimately, providing topline data in the second half of this year.

Lastly, as we move forward with additional pruritic patient populations that may benefit from oral KORSUVA, we are presently planning to initiate Phase 2 trials in both chronic liver disease-associated pruritis and pruritis associated with atopic dermatitis.

We've recently completely a Phase 1 trial of oral KORSUVA at multiple tablet strengths in patients with chronic liver disease. The pharmacokinetic parameters were dose-proportional and oral KORSUVA was generally well-tolerated with no unexpected safety signals reported. Based on this data, we expect to initiate a Phase 2 trial in the second quarter of this year.

We also expect to initiate a Phase 2 proof of concept trial of oral KORSUVA in atopic dermatitis patients around the middle of this year and we look forward to updating you on the details of this trial when we have it under way.

So, overall, we have a very significant year ahead of us here with multiple late-stage trials expected to read out and an ongoing expanded development pipeline for additional pruritic populations we look forward to providing progress updates across all of these programs in the coming months.

With that, I'll now turn the call over to Mani, who will discuss our financial results. Mani?

Mani Mohindru -- Chief Financial Officer and Chief Strategy Officer

Thank you, Derek. As a reminder, the full financial results for the fourth quarter and full year 2018 can be found in a press release issued today after the market closed.

For the full year ended December 31st, 2018, we reported a net loss of $74 million or $2.06 per basic and diluted share, compared to a net loss of $58.1 million or $1.86 per basic and diluted share for 2017. For the fourth quarter of 2018, we reported a net loss of $20.7 million or $0.52 per basic and diluted share compared to a net loss of $14.2 million or $0.43 per basic and diluted share for the same quarter of 2017.

Revenues for the year ended December 31st, 2018 were $13.5 million as compared to $911,000 in 2017. Revenues in 2018 were primarily related to our license agreement with Vifor Fresenius versus revenues of $843,000 in 2017 related to a sublicense fee received from a partner, Maruishi Pharmaceuticals, in connection with their sub-license agreement with Kissei Pharma.

Revenues in 2018 also included $33,000 from sale of clinical compound compared to compound to Maruishi as compared to $68,000 in clinic and compound revenue in 2017. For the fourth quarter of 2018, we recognized revenue of $5.5 million related to the Vifor Fresenius collaboration agreement. We did not recognize any revenues during the fourth quarter of 2017.

Research and development expenses were $75.5 million for the year ended December 31st, 2018 as compared to $48.5 million in 2017. The higher R&D expenses in 2018 were primarily due to the increase in clinical trial cost as well as increase in stock compensation and payroll-related expenses.

For the fourth quarter, we reported R&D expense of $22.8 million as compared to $11.6 million in the same period of 2017, again, due to increase clinical trial and personnel-related costs. General and administrative expenses of $15.3 million in 2018 compared to $11.9 million in 2017. The higher G&A expenses in 2018 were mainly due to increase in stock compensation in payroll and consultant-related expenses partially offset by decreased rent and related costs.

G&A expenses were $4.7 million during the fourth quarter of 2018 compared to $3 million in the same period of 2017. Other income was $3 million for the full year 2018 compared to $1.2 million for 2017. The increase in 2018 was primarily due to higher balance of investments in this period. Other income was $1.2 million in the fourth quarter of 2018, compared to $368,000 in the same period of prior year.

As of December 31st, 2018, our cash, cash equivalents totaled $182.8 million compared to $92.6 million at the end of 2017. The increase primarily resulted from net proceeds of $92.1 million from the company's follow-on offering in July, proceeds of $70 million related to the license agreement with Vifor Fresenius, which included an upfront payment of $50 million in cash and $20 million of equity investment at premium and the proceeds from exercise of stock options.

Turning to our financial guidance, based on the projected costs of our clinical development plans and timing expectations, we expect that our current cash, cash equivalents as of December 31st, 2018 will be sufficient to fund our operating expenses and capital expenditure requirements into 2021 without taking into account any potential milestones under existing collaborations.

I'll now turn back the call to the operator for Q&A.

Questions and Answers:

Operator

Ladies and gentlemen at this time, if you have a question, please press the * then the number 1 key on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the # key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated.

And our first question is from Chris Howerton from Jefferies. Your line is now open.

Chris Howerton -- Jefferies -- Analyst

Great. Congrats on the quarter and all the progress and thanks for taking the question. I think Derek, the main question that I have is maybe just helping contextualize the interim analysis, the powering analysis that was performed earlier this year. I know that you kind of described the process, but it might be helpful, at least from my side, to better understand what the other potential outcomes would have been. So, let's say that they didn't say you needed to increase the sample size. What would have triggered that? Maybe you could help us understand what the alternative outcomes could have been.

Derek Chalmers -- Chief Executive Officer, President, and Director

Sure. Hi, Chris. Thanks for that. So, this is really set up in the standard way for this type of analysis. What we ask the IDMC to calculate is the required sample size to maintain a desired statistical power to see a difference between the two groups in the study. Their possible device in relation to that was graded by sample size.

So, there was a possibility to increase the sample size to X, which was less than maximum to maintain that power or to increase it to Y, which was full sample size in the study, which was up to 500 or there was a possibility to not increase the sample size as the desired power to maintain a difference between the two groups was evidently maintained. Remember, of course, the IDMC runs this analysis in an unblinded fashion.

That was the specific advice we received for the IDMC. What that tells us is there are assumptions, again, made based on our odds ratio or effects size observed in Phase 2B were correct in terms of the required sample size to maintain a high-level of power to see a difference between the two groups. So, really what they're modeling and their analysis is maintaining a threshold of statistical power to maintain a difference.

Chris Howerton -- Jefferies -- Analyst

Okay. So, essentially they observed a sufficient effect or powering enabled to meet the initial power assumptions that you had when you designed the trial.

Derek Chalmers -- Chief Executive Officer, President, and Director

Correct. Obviously, we'd extend that threshold at a high level, a conservative level.

Chris Howerton -- Jefferies -- Analyst

Right. Okay. And then for the chronic liver disease Phase 1 trial, I know you described the pharmacokinetics and the safety. There's nothing unexpected. Are there any plans to present those data in a more full way?

Derek Chalmers -- Chief Executive Officer, President, and Director

There is. We're going to present some summary PK data when we initiate that Phase 2 trial. You're going to see some overall exposure data, again, in a similar fashion to the chronic kidney disease Phase 1, where we wanted to essentially maintain an overall exposure that would match the efficacious dose we've used in the hemodialysis patient population. So, you're going to see that data in summary fashion when we initiate the Phase 2.

Chris Howerton -- Jefferies -- Analyst

For the atopic dermatitis trial, I think you mentioned that we'll see some more information about that when the trial is actually up and going. But can you give us any preview in terms of what patient population you're planning to target with that?

Derek Chalmers -- Chief Executive Officer, President, and Director

Yeah. We're going to look at a breadth of patient population. In terms of pathophysiology, we'll be looking at both the mild to moderate and the moderate to severe and obviously, there will be inclusion criteria related to moderate to severe pruritis within those populations.

Operator

Thank you. Our next question is from Jason Gerberry from Bank of America. Your line is now open.

Jason Gerberry -- Bank of America Merrill Lynch -- Managing Director

Thanks for taking my questions. Just on the post-operative applications for 845, have you had any recent FDA interactions? It sounds like maybe there weren't. I know there were potentially some discussions framing the pathway for the POMV indication. Secondly, when we think about the Phase 2 trial for oral KORSUVA in the CKD35 group, can you talk about what you think about as more of a clinically meaningful effect size in that group?

Derek Chalmers -- Chief Executive Officer, President, and Director

Thanks, Jason. To the first of those, POMV, our aim there is to get clarity from the agency, both on the regulatory path there and on safety exposures and have already existing post-op exposures which fit into that particular program if we change the label on that. We will certainly guide when we initiate the next possible POMV trial as to some more detail in relation to regulatory path there. That's something we'll provide.

On the CKD oral, we don't pre-specify clinically meaningful differences. That's really related to statistically significance. There, we will be looking at differences from baseline measuring that on the usual NRS scales in terms of mean changes and worst itching scores, but we don't set those up with pre-specified differences. We simply model those in terms of sample sizes. That's where you're getting at based on effect sizes we've already observed with KORSUVA in established populations. Obviously, the main effect size we model that on is related to CKD-aP and hemodialysis patients.

Jason Gerberry -- Bank of America Merrill Lynch -- Managing Director

Thank you.

Operator

Thank you. Our next question is from David Amsellem from Piper Jaffray. Your line is now open.

David Amsellem -- Piper Jaffray -- Analyst

I had a couple questions about the atopic derm study you're planning to initiate later this year. So, is that going to have a primary outcome measure looking at a 4-point responder analysis or the 3-point responder analysis? Help us understand what your expectations are given that at least in dermatologic conditions for other anti-pruritics, the 4-point responder analysis seems to be something the FDA wants.

Then secondly on the atopic derm program, any color on dosing and how that may or may not differ from the other doses you're evaluating in the CKD and CLD programs? Thanks.

Derek Chalmers -- Chief Executive Officer, President, and Director

Thanks, David. That's a great question. As you know, we've discussed this before in terms of the appropriate endpoint for each of these patient populations. The endpoint we reached for the hemodialysis associated pruritis population was really based on our empirical analysis in relation to our breakthrough application. That was something we looked at in collaboration with the FDA.

That was taking data from patients where we see significant differences in their worst itch scores and correlating that with the quality of life scores and the patient impression of change. And we empirically derived what would be a clinically meaningful change for those particular patients. From that, we derived a number somewhere around 2.5 on an NRS scale would be clinically meaningful and we bumped that to 3. That's what we ended at in the Phase 3 trial that's under way.

You are correct. There has been a dogma in the dermatological populations for a 4-point reduction really based on analysis that was only performed within a psoriatic population, looking at clinical meaningfulness. So, our plan on moving oral KORSUVA into the AD population is indeed to look at that level of reduction as well as mean change from baseline. We will be looking at the 4-point when we move to the dermatological population and we're still continuing with the 3-point, which we've derived empirically with discussion with the FDA for the CKD-associated population.

Operator

Thank you. Our next question is from Charles Duncan from Kanter Fitzgerald. Your line is now open.

Charles Duncan -- Cantor Fitzgerald -- Managing Director

Hi, guys. Thanks for taking my question and congrats on a good year of progress. It looks like a pretty interesting one coming up. A couple of quick questions -- you laid out very nicely the interim analysis criteria in KALM-1. Can you tell us -- is KALM-2 exactly the same or different? Also, when you look on a blinded basis at the patients being enrolled in KALM-2, how does that compare to KALM-1?

Derek Chalmers -- Chief Executive Officer, President, and Director

I can't give you the answer to the last one, Charles, because no one lets me near any sort of data on a blinded basis to look at. So, we don't look at that routinely, but in terms of the design of the pre-specified interim assessment, exactly the same setup as we have for KALM-1, we're going to look at that one when 50% of the patients complete the 12-week treatment period and as I just talked about with Chris, it's going to be the same conditional power analysis.

We remain blinded. The IDMC is unblinded. They look to maintain a conservative level of power, which is the same as KALM-1 to see a statistical difference between the two groups in that trial. It's designed the same way. It's going to be performed with 50% of the patients completing the 12-week treatment period.

Charles Duncan -- Cantor Fitzgerald -- Managing Director

Okay. That's helpful. They don't let you near data on a blinded basis. How about on unblinded?

Derek Chalmers -- Chief Executive Officer, President, and Director

Yeah, the end of the trial, I get to see. That's about it, Charles. It's a horrible life up here.

Charles Duncan -- Cantor Fitzgerald -- Managing Director

Great. Also, on Kalm-3, the 52-week extension study -- I don't know what you call it -- you mentioned a certain number of patients have gotten through six months and then 12 months. That means they continue on the regimen of getting the drug infused in dialysis? How are they doing in terms of concomitant moods or any other qualitative look at how those patients are doing over time?

Derek Chalmers -- Chief Executive Officer, President, and Director

Yeah. There are no other measurements in that particular trial other than safety. But you're correct. Those patients are dosed in exactly the same manner as we use for our Phase 3 trials and in exactly the same manner this drug is going to be used commercially. So, that's three times a week post-dialysis sessions. Just to remind you because the drug is really excreted, we get this deep hole exposure level for the next two days post-dialysis, which maintains the anti-pruritic activity.

So, they're dosed in exactly the same matter, three times a week for up to one year. What I said is we have approximately 125 patients that are through the six-month mark and about 40% of those are up and through the one-year mark. Today, we've had independent data safety monitoring board analysis in that trial. We just completed one this quarter. And there was no unexpected safety signals within that group at all.

Charles Duncan -- Cantor Fitzgerald -- Managing Director

Okay. That's helpful. Then on just a couple of other quick ones because it's been a couple years since I looked into this. The IP on KORSUVA lasts, the new chemical entity lasts through when and then can you help us understand whether or not there's a picket fence around other non-KORSUVA molecules that may extend IP?

Derek Chalmers -- Chief Executive Officer, President, and Director

Yeah. So, there's no -- there's about a dozen issued patents, US patents. Obviously, we've filed worldwide, but there's a dozen US patents, including composition of matter, of course. That patent runs to 2027 without extension. So, with the five years, that goes to 2032. Beyond that, our patent strategy is the normal one. We have obviously use patterns around where we're using the molecule and then beyond that, we also have some formulation-related patterns. And those run into the mid-20, 30s, in fact that we've been working on. So, there is a number of, if you like, fences around the sequences.

In terms of likelihood of anyone breaking those patterns, unlike small organics where that's much more possible in terms of manipulating the chemistry around these heterocyclic rings, with peptide sequence, it's much more difficult to break, Charles.

So, we actually, we think, secured the entire area and as you know, we tested this empirically a number of years ago on tetrapeptide sequences that have high-affinity specifically for the capital receptor and, of course, that's our primary claim in relation to most of those patterns, so very difficult to break a sequence pattern. So, I think we have quite well-controlled in terms of the entire tripeptide sequences that can interact specifically with kappa opioid receptors.

Charles Duncan -- Cantor Fitzgerald -- Managing Director

Last question going back to David's question on atopic derm -- I'm wondering if you have a perspective on kappa opioid mechanism versus MK1 antagonist mechanism. There's a fair amount of activity in terms of pruritis associated with atopic derm with the MK1 antagonist. I know you've placed your bet, but I'd love to hear your perspective on the merits of the two.

Derek Chalmers -- Chief Executive Officer, President, and Director

It's a big opportunity. I think there's room for everybody. There's a significant unmet need in that patient population. Our view is that the endogenous opioid system locally is a very important control mechanism for pruritis.

One of the animal models we've used and the industry uses is injection of a kappa antagonist to produce a fairly severe pruritis in animals. In my view, and as you know, I've done this for a couple of years now, is that agonism is the most potent mechanism when it comes to human therapeutics. I think we have a driving system we're amplifying, which is always nice and it's difficult to antagonize, especially in that situation.

We think we're tapped into one of the main driving systems. So far, that's proven to be correct as we're seeing efficacy across all animal models we look at, regardless of the mechanism. We know from our data and some other Japanese clinical data that this mechanism is in chronic kidney disease and chronic liver disease-associated pruritis. So far, the data would bear out the broad anti-pruritic applicability, but we're going to test that empirically. Stay tuned for about 12 months and we'll have the answer to all of this.

Operator

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

Annabel Samimy -- Stifel Nicolaus -- Managing Director

Hi, thanks for taking my questions. I just wanted to go back to the CLD population. Are there any particular adverse event side effects you might have to watch out for in this population given the complexity of their disease, any problems. With regard to the dose proportionality, should we expect something similar to what you're already looking at in CKD and do you have any sense of the size of the trial?

Derek Chalmers -- Chief Executive Officer, President, and Director

One of the advantages of this chemical class, as you remember, is we don't have any liver metabolism and we don't have any interaction, having performed every possible test on this with any of the CIP enzymes either as a stimulator or inhibitor. So, we didn't predict we'd have specific issues with this patient population, but as you point out, there are a lot of comorbidities there. We wanted to ensure the exposure levels we could maintain there were going to match what we knew was efficacious based on our CKD data. We've done that and we're going to select tablet strengths that are going to give us that.

The difference between this and the CKD oral is going to be we're going to be doing this twice a day. Despite the fact that some liver patients do have some inhibition of renal function, it's not to the level that we saw significant diminishment in excretion. 845 is excreted almost exclusively via the urine. We wanted to establish that and make sure that was the case.

So, safety looks good. We don't see anything different there than we've seen in other populations and when we start that trial, we'll announce the tablet strengths that we're going to use in that particular population, which is going to be very similar in range to the dosages we're using in the CKD Stage 3 to 5 patients, the difference again being there we can dose once a day. That's likely to be twice a day dosage.

Annabel Samimy -- Stifel Nicolaus -- Managing Director

Just on the opportunity in CLD, you mentioned CKD is about 2.5 in Stage 3 to 5 chronic kidney disease. Is CLD similarly sized? Is it much larger or smaller? Can you give us a sense there?

Derek Chalmers -- Chief Executive Officer, President, and Director

We looked at that in a similar fashion looking at script numbers rather than epidemiological numbers and using ICD-9 codes to cross that with the various disease states in liver. Various liver conditions are associated with moderate to severe pruritis. Viral infections, hep B, and hep C, some NASH patients, some cirrhosis patients. When you add all those up and look at that population in the US and, as we know, some of the medications associated with liver disease situations can also induce pretty severe pruritis.

When we add all of those up, it looks like somewhere around a couple of million scripts a year when we look at all of those conditions. So, that's a significant opportunity there, which is somewhat similar to the pre-dialysis CKD opportunity. And then, of course, when you get to atopic, that's a different magnitude there in terms of potential addressable patient population.

Annabel Samimy -- Stifel Nicolaus -- Managing Director

While we're on the atopic dermatitis topic, it's been an elusive disease to treat from a pruritic perspective. Are there any teachings or anything you can learn from other trial shortcomings, trial failures that you can apply to your program that might help with a better outcome?

Derek Chalmers -- Chief Executive Officer, President, and Director

In reality, Annabel, most of the pruritis models that we use and the industry uses are dermatological, of one sort of another, and we certainly had KORSUVA through all of those and showing great effect, certainly in contrast to some other mechanisms in those models, but at the end of the day, there really hasn't been a selected and peripherally acting kappa tested in that population. Everything that's been used today has been less selective or partial in terms of agonism.

So, we feel as though there hasn't been an appropriate test yet. And that patient population -- and we'll be careful how we select patients coming into that trial. So, mechanistically, that's something we have to look at empirically, but based on all the data we generated both pre-clinically and the fact that it seems to work as this mechanism, peripheral kappa across other patient populations, we're optimistic that we can have a beneficial effect within that patient population.

Annabel Samimy -- Stifel Nicolaus -- Managing Director

Okay. Great. Thank you.

Derek Chalmers -- Chief Executive Officer, President, and Director

Thanks, Annabel.

Operator

Thank you. As a reminder, ladies and gentlemen, if you have a question, please press the * and the number 1 key on your touchstone telephone. And our next question is from Arlinda Lee from Canaccord. Your line is now open.

Arlinda Lee -- Canaccord Genuity -- Analyst

Thanks for taking my questions. Can you remind us on what the exposure requirements are for filing and what you'll have by that time? You mentioned some statistics on the label extension and I'm curious how many more patients or duration you'll need to have by the time you file. Also, you've talked about getting additional regulatory clarity on the post-operative payment. I'm wondering how high of a priority is that for you guys right now. Thanks.

Derek Chalmers -- Chief Executive Officer, President, and Director

On the last one, as you know, as we've said, our main priority here is pruritis and that's where we're focusing our effort. The PV effort is really to get clarity in relation to the endpoints required there for labeling regulatory path and then some clarity on some of the work we've done so far there in terms of safety exposures. With that package, I think we've be in a much stronger position to look for an appropriate partner to come in and help fund any effort on the PV side. That's the strategy related to that application.

For the first question, ICH guidelines and exposures for the KORSUVA injection program are 1,500. That's how we've designed our program. Both he Phase 3s that are ongoing have safety exposure extensions beyond those trials. We started the 52-week study I mentioned on the call in 2017. We've been making sure we can get to those exposure levels and looking for ways to add up exposures to get the fastest possible path to NDA.

As you know, it's a breakthrough-designated compound. There is a possibility that we can file with less safety exposures with such a compound. It's certainly something we will exposure with the FDA. We're not counting on that path, but once we have our first US-based KALM-1 pivotal data, it's certainly something we'll explore with the FDA, but we've designed our whole program to accommodate normal ICH guidelines, which is 1,500 exposures.

Operator

Our next question is from Alan Carr from Needham. Your line is now open.

Alan Carr -- Needham & Company -- Analyst

Thanks for taking my questions. To follow-up on the last one, is it feasible for you all to file MBA/MAA by the end of this year after creating both KALM-1 and KALM-1 and can you also comment on what non-clinical work or items are needed for the NDA. Where do those stand? Thanks.

Derek Chalmers -- Chief Executive Officer, President, and Director

All right, Alan, let me take the last one first. Non-clinical work, we're basically complete, almost everything we need in the non-clinical sense, pre-clinical sense is finished. So, what we're working on now is, as you point out -- we're looking to complete our pivotal KALM-1 and KALM-2 studies and then our safety extension studies on both of those, of course, and then file as quickly as we can afterwards.

We'll be able to guide more fully, more accurately, if you like on this, a little later this year, once we have our readouts from KALM-1 and we know where we are with KALM-2 and we advance our 52-week safety study, this is something we can guide to a little later this year.

Alan Carr -- Needham & Company -- Analyst

What sort of meeting would that be with the FDA after your first Phase 3? Would that be a formal into Phase 3? How would that work?

Derek Chalmers -- Chief Executive Officer, President, and Director

With a breakthrough designation, we can request meetings fairly frequently. We probably reserve our pre-NDA meeting for a little later. We use another standard meeting to interact with the NDA.

Alan Carr -- Needham & Company -- Analyst

Then the last one, any updates on any of your collaborations in Japan or Korea in terms of how they're progressing in development?

Derek Chalmers -- Chief Executive Officer, President, and Director

Both are progressing, the CKD or Chong Kun Dang Pharma is working with us in relation to Korean participation and the global Phase 3. Maruishi, as you know, has sublicensed hemodialysis patients to Kissei and they're advancing that program well. We'll certainly report outcomes in both of those areas when we see the data.

Alan Carr -- Needham & Company -- Analyst

Thanks for taking my questions.

Derek Chalmers -- Chief Executive Officer, President, and Director

Thanks, Alan.

Operator

Thank you. Our next question is from Esther Hong from Janney. Your line is now open.

Esther Hong -- Janney Montgomery Scott -- Analyst

Hi, thanks for taking my questions. So, my first one is on partnerships over IV KORSUVA in hemodialysis patients. So, in the US, you've got a significant partnership with Vifor Fresenius, one of the largest dialysis center owners in the US. So, have you had discussions with the other largest owner, DaVita? Do the terms of your Vifor Fresenius agreement allow you to also partner with DaVita? Beyond that, how would IV KORSUVA roll out commercially in the Fresenius clinics? Would they be specific to certain regions? Could we imagine they would be in the majority of clinics? How would it look?

Derek Chalmers -- Chief Executive Officer, President, and Director

Thanks, Esther. So, the deal we have, the license agreement with have with Vifor Fresenius is really focused on ex-US, so they have European rights and some territories in the Asia-Pacific region, obviously not Japan and South Korea. Within the US, we have a co-promotion agreement specifically in Fresenius clinics. That's about 38% of the patient population in the US. So, the vast majority, I guess 62%, remains solely in Cara's purview and we are free to market within the population solely and we will do so and are planning to do so. So, that's the difference in setup.

What was your other question in relation to Fresenius? Oh, so, the Fresenius arrangement in no way restricts us in how we can interact with other dialysis providers in the US. We can set up any type of copromotion licensing agreements with any of these dialysis providers.

Esther Hong -- Janney Montgomery Scott -- Analyst

Do you expect to have discussions with DaVita?

Derek Chalmers -- Chief Executive Officer, President, and Director

We do. As we advance our commercial plans, we will be -- not only DaVita but some of the other major independent dialysis providers we'll be talking to.

Esther Hong -- Janney Montgomery Scott -- Analyst

Great. Thank you.

Operator

Thank you. At this time, I am showing no further questions. I would like to turn the call back over to Derek Chalmers for closing remarks.

Derek Chalmers -- Chief Executive Officer, President, and Director

Thank you. Thank you, everybody for participating in today's call. I'd like to thank the Cara team for their continued hard work and commitment and to supporting our various programs, our study investigators, and most importantly all of the patients who continue to participate in our clinical trials. Thank you to everybody and we look forwarded to updating you very, very soon. Thank you very much.

Operator

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

Duration: 51 minutes

Call participants:

Jane Urheim -- Stern Investor Relations

Derek Chalmers -- Chief Executive Officer, President, and Director

Mani Mohindru -- Chief Financial Officer and Chief Strategy Officer

Chris Howerton -- Jefferies -- Analyst

Jason Gerberry -- Bank of America Merrill Lynch -- Managing Director

David Amsellem -- Piper Jaffray -- Analyst

Charles Duncan -- Cantor Fitzgerald -- Managing Director

Annabel Samimy -- Stifel Nicolaus -- Managing Director

Arlinda Lee -- Canaccord Genuity -- Analyst

Alan Carr -- Needham & Company -- Analyst

Esther Hong -- Janney Montgomery Scott -- Analyst

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