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

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.