Edited Transcript of CARA earnings conference call or presentation 7-May-19 8:30pm GMT

As many of you know, KORSUVA is 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. Our lead development program is KORSUVA Injection for chronic kidney disease associated pruritus, or CKD-aP, in hemodialysis patients where we currently have 2 ongoing pivotal Phase III trials, designated KALM-1 and KALM-2.

Earlier this year, we announced we've completed enrollment of the KALM-1 trial. We're happy to note that as of today, all patients in KALM-1 have now completed their treatment period and last visits, and we're on track to report top line data a little later this quarter.

Additionally, based on current enrollment progress, we also expect to report top line data from KALM-2 in the second half of 2019. We're also making good progress in advancing the development of Oral KORSUVA across a number of patient populations where pruritus continues to be a significant unmet need. Firstly, our ongoing Phase II trials in predialysis stage III-V CKD patients with moderate to severe pruritus is enrolling well. And top line data is expected here in the second half of 2019. Additionally, we plan to initiate 2 other Phase II trials in non-CKD patient groups. The first in chronic liver disease associated pruritus a little later this quarter and the second in atopic dermatitis around midyear.

So overall, we remain well positioned to execute on our lead pivotal Phase III program for CKD-aP in hemodialysis patients as well as progress our Oral KORSUVA programs across multiple patient populations through 2019.

Before we provide overview on each of our ongoing programs, I want to briefly remind you of KORSUVA's mechanism of action and why we believe it has the potential to be a first-line therapy for pruritus across patient populations. KORSUVA's therapeutic 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 blocks the release of a 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 effective antipruritic action regardless of the initiating pathophysiology, whether that's chronic kidney disease, chronic liver disease, a dermatological condition or some other clinical situation.

So moving on to our clinical programs, let's start with KORSUVA Injection for hemodialysis patients with CKD-aP. This is a patient population where moderate to severe pruritus occurs in approximately 40% of patients. It significantly diminishes quality of life and is associated with increased morbidity and indeed mortality. The FDA has granted KORSUVA Injection breakthrough therapy designation for this indication, reflecting the significant unmet need with no therapeutics approved in the U.S. or indeed Europe at this point. The pivotal program for KORSUVA Injection in this patient population currently includes 4 ongoing Phase III studies. KALM-1, a U.S. efficacy trial, KALM-2, a global efficacy trial and 2 open-label safety studies, 1 U.S. and 1 global, and I'll cover each of these shortly.

Both KALM-1 and KALM-2 are designated -- are designed to investigate the efficacy of KORSUVA Injection at a dose of 0.5 micrograms per kilo versus placebo. The drug is administered 3 times per week after scheduled dialysis sessions over a 12-week treatment period with a 52-week open-label extension phase for safety. The primary efficacy endpoint is 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 measured on a standard Numeric Rating Scale.

Secondary endpoints in the trials measure aspects of itch-related quality of life, using validated self-assessment scales, namely the Skindex-10 and the 5-D itch, both of which we had also previously employed in our completed Phase IIb trial. Additional secondary endpoints include the proportion of patients achieving a greater than or equal to 4-point improvement from baseline and weekly mean of the daily 24 worst itch NRS score at week 12.

The third ongoing Phase III trial in our pivotal program is an open-label, 52-week extension safety study, which we initiated in 2017. We recently expanded this trial to enroll up to 300 patients from 240 patients with currently about 150 patients through 6 months of treatment and approximately 40% of these patients completed 1 year of exposure. To date, the safety and tolerability has been consistent with the data reported in Phase II trials of KORSUVA Injection in hemodialysis patients. And based on completed independent data safety monitoring board evaluations, the last of which was in Q1 of this year, no new safety signals have been observed to date.

In addition, with the aim of accelerating safety exposures to KORSUVA Injection, we've recently initiated a second open-label safety study, utilizing both U.S. and European clinical sites. And to clarify, this is not a trial required for any specific request from any regulatory agencies but rather part of our regulatory strategy to utilize novel clinical sites and accelerate required safety exposures per ICH guidelines in an effort to further expedite our path to NDA filing. This trial is expected to enroll up to 400 patients with a maximum treatment period of 12 weeks.

So with top line data from both KALM-1 and KALM-2 expected this year and rapidly accumulating long term and total patient safety exposures from the ongoing open-label trials, we do remain on track toward our goal of developing KORSUVA Injection as a first-in-class therapeutic for hemodialysis patients suffering from pruritus as quickly as we possibly can.

We also remain focused on advancing Oral KORSUVA for predialysis patients with moderate-to-severe CKD-aP. Based on generic pruritus-related script numbers, it is estimated there are at least 2.5 million stage III-V CKD patients suffering from pruritus in the U.S. with current standard of care being predominantly generic corticosteroids and antihistamines.

So we're currently evaluating Oral KORSUVA in an ongoing U.S. Phase II trial for predialysis CKD-aP patients. This trial is a multicenter, randomized, double-blind, placebo-controlled 12-week trial, designed to evaluate the safety and efficacy of 3 doses of Oral KORSUVA, 0.25-milligrams, 0.5-milligrams and 1-milligram tablet strength administered once daily. In this Oral KORSUVA Phase II trial, we're enrolling 240 patients with 60 per arm. There's an unblinded interim power assessment at 50% enrollment for those subjects who have completed 12 weeks of treatment that allows for expansion of the study up to 480 patients. This trial is currently on track for patient enrollment, and we expect to complete the interim assessment in the next few 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 plan to initiate 2 additional Phase II trials in the near term. The first, in chronic liver disease-associated pruritus in Q2 and the second in pruritus associated with atopic dermatitis around midyear. And we will provide more detail around trial design and patient selection for both of these trials upon initiation.

So overall, we're very pleased with our team's execution and all of the progress across our clinical program so far this year. And we look forward to providing further updates as we advance KORSUVA through several significant clinical milestones in the coming months.

And with that, I'll now turn the call over to Mani to discuss our Q1 financial results. Mani?

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Mani Mohindru, Cara Therapeutics, Inc. - CFO & Chief Strategy Officer [4]

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Thank you, Derek. As a reminder, the full financial results of our first quarter of 2019 can be found in the press release that was issued earlier today after market closed.

For the first quarter of 2019, we reported a net loss of $22 million or $0.56 per basic and diluted share compared to a net loss of $16.8 million or $0.51 per basic and diluted share for the same quarter of 2018.