Good afternoon, and welcome to the Cara Therapeutics Fourth Quarter and Full Year 2015 Earnings Conference Call. At this time, all participants are in a 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 Cara's team, please proceed.

Good afternoon. This is Jesse Baumgartner with Stern Investor Relations. And welcome to Cara Therapeutics fourth quarter and full year 2015 earnings conference call. The news release with our fourth quarter and full year financial results and corporate update became available at 4:01 PM today, and can be found on our Web site at www.caratherapeutics.com. You may also listen to a live webcast and replay of today's call on the Investors section of our Web site. 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 includes statements concerning a expected timing of the Company's meeting with the FDA to discuss the clinical hold for I.V. CR845 in post-operative pain, the potential resolution of the clinical hold and resumption of the CLIN3001 trial, timing for the Company’s other planned clinical trials and the reporting of clinical trial results, the potential results of ongoing and planned clinical trials and future regulatory development milestones for the Company’s product candidates, and the Company’s 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. The 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, 2015 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward-looking statements made on today's call speak only as of the date on which they are made. Cara Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made except as required by law. Now, let me turn the call over to Cara's President and CEO, Dr. Derek Chalmers.

Okay. Thank you, Jesse. Good afternoon everybody. Thanks for being with us on the call. I'm joined today by our Chief Medical Officer, Joe Stauffer; and our Chief Financial Officer, Joe Schoell. So the agenda for today's call is as follows, I'll provide a brief overview of our 2015 highlights and also recent developments. Then Joe Stauffer will walk through the status of our pivotal trial of CR845 in acute post-operative pain, as well as an ongoing development plans for our CR845 programs in uremic pruritus and also in chronic pain. And then Joe Schoell will walk through financials for the fourth quarter before we open up to Q&A. So 2015 was certainly a very productive year for us at Cara. We continue to execute on our clinical development plan and build out a broader set of indications for CR845. Starting with our lead indication for I.V. CR845 in acute post-op pain, we initiated our first adaptive pivotal trial CLIN3001 in September of last year. Examining repeat doses of CR845 administered both prior to and following abdominal surgeries. As we discussed with you a couple of weeks ago, we recently announced that the trial has been placed on a clinical hold, following a limited number of patients reaching a pre-specified stopping rule related to increases in serum sodium concentrations to the mild to moderate hyponatremia level that is greater than or equal to 150 Millimoles Per Litre and I’ll remind you the normal range is 135 Millimoles Per Litre to 145 Millimoles Per Litre. Again to remind you that there were no severe adverse events observed in these patients and all sodium levels will result to normal levels within 24 hours through standard fluid management protocol. Nevertheless, we’re working through a review of safety data by both us and the…

Thank you, Derek. I will be starting with our first adaptive pivotal trial in acute post-op pain CLIN3001, and just as a reminder of the structure of this study. This is a multi-center randomized double-blind placebo-controlled parallel group adaptive design trial with repeated doses of I.V. CR845 or placebo administered both prior to and following abdominal surgery in male and female patients at approximately 30 sites in the U.S. The trial is designed to enroll up to 600 patients undergoing various abdominal surgeries. As we discussed previously, the study accommodates interim assessment for safety and conditional power across the doses with an adaptation to optimum doses and subsequent progression to complete enrollment. As Derek noted, following a protocol specified trial safety review after 90 patients have completed dosing, we identified that the pre-specified stopping rule related to the number of patients exhibiting increases in serum sodium concentration to the mild moderate hyponatremia level to find as greater than or equal to 150 Millimoles Per Litre have been reached. The review of the unblinded safety data show that the four patients were confined to the highest CR845 dose group, that’s the 5 microgram per kilogram group. They’re asymptomatic and as with our previous experiences, sodium levels resolved to normal level which is less than 146 millimole per litre with standard fluid management, no patients in the other two groups, which is the 2 microgram group and the 1 microgram group exhibited serum sodium levels greater than 150. Importantly, the review also showed that there were no CR845-associated serious adverse events thus far in the trial and the safety profile overall has been well in line with what we saw in our earlier Phase 2 pain studies with I.V. CR845. Right now, we're focused on completing the protocol safety data review process…

Thanks, Joe. And as a reminder the full financial results for both the fourth quarter and the full year 2015 can be found in our press release issued today after the market closes, the following is a summary of the fourth quarter results. We reported a net loss of 9.5 million or $0.35 per basic and diluted share for the fourth quarter of 2015, compared to a net loss of 4.2 million or $0.18 per basic and fully diluted share for the same period of 2014. We did not recognize any revenue during the fourth quarter of 2015. For the fourth quarter of 2014, we had collaborative revenue of $399,000, comprising of revenue that had been deferred upon entry into a license agreement with Maruishi Pharmaceutical Company and clinical compound revenue was $515,000 from the sale of the clinical compound to Maruishi. R&D expenses were 7.6 million in the fourth quarter of 2015, compared to 3.5 million in the same period of 2014. The higher R&D expenses in the fourth quarter of 2015 were principally due to an increase in direct preclinical and clinical trial costs, consultant services in support of the preclinical studies and clinical trial cost, and an increase in payroll and related costs for R&D personnel. General and administrative expenses were 2.2 million in the fourth quarter of 2015 compared to 1.8 million in the same period of 2014. The increase in the fourth quarter of 2015 was primarily due to increases in payroll and related costs and stock option expense. Those increases in costs were partially offset by decreases in professional and consulting fees. At December 31, 2015, cash and cash equivalents and marketable securities totalled $106.7 million compared to 52.7 million at December 31, 2014. The increase in the balance of cash, cash equivalents and marketable securities resulted from a receipt of the net proceeds of 75.2 million from the follow-on offering of common stock which closed in August of 2015, also cash received from exercise of stock options of 300,000 and partially offset by 21.5 million of cash used in operations. Turning to our financial guidance, based up on timing expectations and projected costs for current clinical development plans, we expect that our existing cash, cash equivalents and marketable securities as of December 31, 2015 will be sufficient for the Company to fund its operating expenses and capital expenditure requirements through the end of the first quarter of 2018, without giving effect to any potential milestone payments under existing collaborations. Now, we'll open it up to Q&A, operator? Thank you.

[Operator Instructions] Our first question comes from Annabel Samimy of Stifel. Your line is open.

I just had a couple of additional questions on clinical hold, so I understand that the timing of the clinical hold is really contingent on the IV NB review completion and then further submissions to the FDA, with some of the recommendations that we've talked about in the past, I guess one of the things I was curious about is, is it if you hadn’t had the protocol violations in the trial, it doesn’t seem like we'd be here today with the clinical hold, so is there a possibility that dropping the dose is too brave step or adjustment in this trial, and if that is the case can you explain how dropping the dose won't compromise the efficacy? Thank you.

Sure, so dropping the dose is certainly a reasonable thing to do I mean obviously that higher dose, and in terms of the other two remaining doses, don’t forget that the 1 microgram per kilogram arm was also efficacious in our itch program that's also consistent with efficacy that we have from pre-clinical evidence. And the other thing that we have working in our favour here is that we also have a pre-planned look at the data as part of the original protocol and they will be part of the follow-on protocol to take the interim assessment look for conditional power. So that's how we protect our flank and downside so to speak for efficacy failure once we get to about 50-60 patients randomized per arm.

And then on the uraemic pruritus trial, you gave us the study designed to may be two parts with Q3, but these two parts are you going to have any additional clinical trial requirements after that?

Well since [indiscernible] we will very likely have to do another pivotal trial as well. And following the same type of requirements that we would expect from any NCE you can expect that we’ll have to have a similar type of data base as well, 1,500 total exposures as part of the entire program. So, to sum that up, it would be this trial plus another pivotal trial Phase 3.

And so if that’s the case and can you sort of give us an idea of when we might be looking at this in terms of potential filing?

Yes Joe answer it.

So in terms of filing the NDA?

Yes, I think it's too early to say on it until we get this initiated and actually look at the equipment rates for the number of sites we’re going to have involved here that is -- we’ll give guidance on that as we get underway we know how quickly we can recruit patients into these trials.

Our next question comes from Charles Duncan of Piper Jaffray. Your line is open.

This is Sarah on for Charles. So, in terms of the clinical hold besides from the cases of hyponatremia, were you otherwise encouraged by the interim look of safety of CR845?

Very much though. I mean none of these patients, none of any of the patients have serious adverse events related to serum sodium, so very encouraging that is similar to what we’ve seen before in previously trials.

And then what do you believe that agency is working on or looking for in advance of a meeting with your next quarter?

Right so, what they’ll look for is our proposal based on the IDMC recommended guidance and our agreement to that guidance that we will likely come up with a dosing scheme that make sense that keep patients less than the 150 target.

Our next question comes from Alan Carr of Needham & Company. Your line is open.

What about -- with these Phase 3 trials in uraemic pruritus be running in serial or could you do them, would they just be staggered? And then with your hope to reinitiate the Phase 2/3 in post-operative pain in second quarter what are your thoughts on timelines to the interim assessment and the final results from that trial?

Sure. So the first part of your question was related to UP and we would run the staggered because we want to optimize the dose. The second part of your question was related to the I.V. pain trial, is that correct. And you’re looking for timing there. We’ll have a better sense of what that timing looks like once we meet with the FDA, finalize the protocol going forward, get a handle on sample size and get up and running. So we’ll be able to comment with more clarity once we have that meeting.

I mean is it appropriate to assume that you started this one back in September, and should we just -- and you I think have been guiding for finishing it in 3Q. Should we just shift everything out six months, or what sort of factors might influence that?

I don’t know if it's necessary to assume that at this point. We have to see what the size of the trial looks like. I would anticipate the trial size gets smaller, which is good and smarter, which is also good. But, as I said, I’ll have a better sense of what that looks like once we got agreement with the agency what the full scope of trial looks like.

And then last one in terms of revenues for 2016, are there any milestones that you all expect from Maruishi or CKD this year or maybe you can give us an update on where they stand with clinical development over there?

As far as milestones for Maruishi Alan we don’t expect any in 2016. There will be in 2017 though.

Our next question comes from Ken Trbovich of Janney. Your line is open.

Just wanted to follow-up on the discussion for uraemic pruritus, I think part of the curiosity that I have is that the design or the intention to go forward with an oral formulation study before you’ve even figured out what the optimal dose is on the I.V. side. Can you kind of help us understand how you’re trying to bracket that?

Yes, I’ll let Joe talk about clinically Ken but to start there for us in a market sense and for reimbursement of that product ultimately as you’re well aware an intravenous product in the U.S. is essentially automatically within the bundle payment. And as you’re also aware an oral medication is automatically outweigh the bundle payment and falls into Medicare Part D, so this is part of a stat program we’re trying to initiate to essentially validate the oral in these patients so that not only we could think about transferring from I.V. to oral for uraemic pruritus and then it makes it much-much easier to walk that back to chronic kidney disease obviously. But also ultimately to possibly expand beyond dialysis associated pruritus into those other conditions that you’re well aware of associated with liver disease and endocrine disorders and so on where there is a very-very significant unmet need in terms of general pruritus, so that's our initial step in validating our formulation with an ability to move to that formulation for UP and possibly other conditions.

Sure. No I understand with regard to the intention from the reimbursement standpoint and even outside of UP potentially but obviously this PK study in hyponatremia was outside of UP I guess, what I'm really trying to get at is it is the first study tested three doses and had the same Part a, Part b design and the Part b design was highly affected at a 1 microgram dose and so I'm -- I guess, I'm a little puzzled around, first the FDA’s request that you guys do a three dose study and then secondly, what's the -- when we talk about the PK study or just looking at it purely from a oral proof of concepts in that patient population or is this really trying to refine a specific dose because it's not clear to me, that you'd be able to target specific dose until this first trial is completed.

Right, now on the first part of that question, Joe can chip in on this standard protocol for the FDA to look for dose responsiveness and establishment of minimal effect of dose and that's why we're going to look at a dose range in the first, two, three trial and the second part is the simplest way to look at it, as we quantified the tablet strength that can narrow a much AUCs, we know our effect of from our intravenous studies. And that’s something we can run with a PK trial in these patients we haven’t done it before in these patients and simply to establish that we can get bioequivalence if you like in terms exposure and then to find the tablet strength or strengths that we would predict would active in this group, that's the main reason to run that trial.

Okay. And then the three doses over the same three doses that we saw in the earlier spend?

The three doses in terms of the intravenous trial while they're going to be anchored during the 1 microgram per kilo and I think as we have said before, it is highly likely we’d like to look at a dose lower than that to sign floor and it's also highly likely we’d look at a dose higher than that.

Right and then I guess, the reason I'm asking is that the earlier study was 0.5 and 2.5, so I'm just trying to confirm whether or not we're talking about the same doses or you're looking at different doses outside of those two that were already tested?

Yes, that's undecided at that point Ken, but we will certainly go to that when we know final dosages.

Okay and then last question, I know the question with regard to timeline on the program overall was considered too long in the distance too sort of refined but could you give us an expectation on your perspective in terms of how quickly this particular study could be completed because I know you and a competitor both had fairly rapid enrolments in earlier studies, so I just didn't know what you thought the timeline for completion of this study would be on the I.V. side?

As with the I.V. post-op Ken I think we like to get to that once we're up and running and we know how quickly sites are recruiting then we'll make a guidance on that but we aim to get the study up and running first half of this year. So, you are not too far away from more refined guidance once we get the study underway.

Sounds good. Okay, appreciate your time.

Our next question comes from Chiara Russo of Cantor Fitzgerald. Your line is open.

Just probably back tracking and I apologize if this has already been addressed. I jumped on the call late, but I was wondering if you could just walk us through sort of the dose equivalent math if you will around the 2 microgram and the 5 microgram, why sort of efficacy here is looked at for areas under the curve versus CMAX? And why you feel comfortable sort of translating that 1 microgram dose that you saw in pruritus over to the pain trial? Thank you.

Sure, so I'll start with the back end of your question first, pain and itch travel along the same receptors on the A-delta and C-fibers on ascending pathway, whether it's coming from your skin or whether it's coming from a surgical insult, and we know that the 1 microgram per kilogram is quite efficacious even with only and I think 30 patients per treatment arm in that I.V. UP study and then like fashion, so extrapolate that then out to what we knew in the [indiscernible] trial of [indiscernible] inflammatory painful model, in that situation we had 5 micrograms per kilogram at two 8 dosing, and we saw nice efficacy there as well. But we needed to go lower, we wanted to go lower because we thought we could even optimize the doses lower, in other words deliver ALG's efficacy at a lower dose, it's a very potent drug, and not have to deal with side effects going forward. Clearly we have one of those side effects at the [indiscernible] but it doesn't scare me or bother me at all actually at this point yet about the 1 and 2, because what I just said on IVH and we'll be able to take a look at that dose again in the assessment once we get a healthier complement of patients for treatment on to see that conditional power, if indeed we have conditional powers it makes us feel comfortable going forward then we continue that study, if we don't we readjust depending upon what we see.

There are no further questions. I would like to turn the call over Derek Chalmers for any closing remarks.

Okay well thank you everybody for participating in today's call and we look forward to updating you again very-very soon, so thank you very much.