Edited Transcript of CARA earnings conference call or presentation 12-Mar-19 8:30pm GMT

Thank you, Jane, and good afternoon, everybody, and 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 pruritus 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 III program of KORSUVA Injection for chronic kidney disease associated pruritus or CKD-aP in hemodialysis patients with the initiation of our 2 pivotal Phase III trials designating 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 top line data from this trial in the second quarter of this year as well as top line data from KALM-2 in the second half of this year.

Our ongoing Phase II trial of Oral KORSUVA is enrolling pre-dialysis Stage III to V CKD patients with moderate-to-severe pruritus with top line data expected here in the second half of 2019. We also plan to initiate a Phase II trial of Oral KORSUVA in patients with chronic liver disease associated pruritus or CLD-aP in the second quarter following the recent completion of our Phase I pharmacokinetic and safety trial. And then lastly, we anticipate initiating a multi-dose, proof-of-concept Phase II trial of Oral KORSUVA in atopic dermatitis patients with moderate-to-severe pruritus around the middle of this year. So overall, we're well positioned to execute on our lead pivotal Phase III program for CKD-aP and HD patients as well as progress our Oral KORSUVA program 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 antipruritic agent across clinical conditions.

KORSUVA is, of course, our novel first-in-class selective peripherally acting kappa opioid receptors 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 afferents as well as on certain immune cells. The action of KORSUVA on dermal and epidermal immune cells locks the release of a range of nerve-sensitizing molecules or pruritogens diminishing the stimulation of dermal sensory fibers and we believe that this dual neuronal and anti-inflammatory effect of [Ford's] KORSUVA, an effective antipruritic 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 in hemodialysis patients with CKD-aP. As a brief reminder, the late-stage clinical program for KORSUVA Injection in this patient population currently includes 3 ongoing Phase III studies: the KALM-1 study, a U.S. 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 power 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 for the prespecified interim conditional power assessment conducted after approximately 50% of the targeted patient numbers completed the 12-week treatment period. And to further clarify on this analysis, given the prespecified decision rule and the formula used for calculating 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 III trial. Following the IDMC recommendation, we completed enrollment of approximately 350 patients in KALM-1, and we're on track to read out top line data from this trial in the second quarter.

Our second pivotal trial KALM-2 is also designed with a prespecified interim assessment, again, after approximately 50% of patients completed the treatment period. And similarly to KALM-1, we look forward to providing the result of this analysis ahead of top line 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 recall, administered 3x per week after scheduled dialysis sessions over a 12-week treatment period. The primary efficacy endpoint as the 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 IIb trial. Additional secondary endpoints include the proportion of patients achieving a greater than 4-point improvement from baseline and the weekly mean of the daily 24-hour worst itching scores at week 12.

The third ongoing Phase III trial in our pivotal program is an open-label, 52-week extension study designed to evaluate the safety of KORSUVA Injection in up to 240 patients. We now have close to full enrollment in this study, with about 125 patients through 6 months of treatment and approximately 40% of these patients passed the 1-year exposure level. To date, the safety and tolerability have been consistent with data reported in Phase II trials of KORSUVA Injection in hemodialysis patients and based on our recently completed independent data safety monitoring board evaluation, no new safety signals have been observed in this study.

With top line 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 pruritus, 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 pruritus-related script numbers that is estimated, there are approximately 2.5 million Stage III to V CKD patients suffering from pruritus in the U.S. with current standard of care being predominantly generic corticosteroids and antihistamines. We're currently evaluating Oral KORSUVA in an ongoing U.S. Phase II trial of nondialysis 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 3 doses of Oral KORSUVA of 0.25 mg tablet, 0.5 mg tablet and a 1 milligram tablet administered once daily. From a Phase I 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 achieves statistically significant effects in both primary and secondary endpoints in our completed Phase IIb trial. In this Oral KORSUVA Phase II trial, we expected to enroll 240 patients with 60 per arm. There's an unblinded interim power assessment at 50% enrollment for those who've 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 you with an update on the interim assessment in the coming months, and ultimately, providing top line 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 II trials in both chronic liver disease associated pruritus and pruritus associated with atopic dermatitis. We've recently completed a Phase I 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 best data, we expect to initiate a Phase II trial in the second quarter of this year. We also expect to initiate a Phase II 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 underway.