Good afternoon, and welcome to the Cara Therapeutics first quarter 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 the Cara team. Please proceed.

Good afternoon. This is Jesse Baumgartner with Stern Investor Relations. And welcome to Cara Therapeutics first quarter 2015 earnings conference call. The news release with our first quarter financial results and corporate update became available at 4 o'clock PM 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 includes statements concerning the expected timing for the company's clinical trials and the reporting of clinical trial results, the acceptability to the FDA of the company's proposed Phase 3 Program for I.V. CR845, the potential results of ongoing and planned clinical trials and future regulatory and development milestones for the company's product candidates, and the potential for CR845 to provide a new therapeutic approach to treating uremic pruritus. 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, 2014 and its other documents subsequently filed with or furnished to the SEC. All forward-looking statements made on today's call speak only as of the date on which they were 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. Now, let me turn the call over to Cara's President and CEO, Dr. Derek Chalmers.

Thanks, Jesse, and good afternoon, everyone. Thanks for being with us on the call this afternoon. I am joined today by our Chief Financial Officer, Josef Schoell; and our Chief Medical Officer, Dr. Joseph Stauffer. So the first part of '15 has certainly been an exciting time for us here at Cara, as we continue to make a number of important strategic planning decisions that will direct our clinical activity during the next 12 to 18 months. These include: finalizing our lead Phase 3 program for I.V. CR845 in acute pain, after End-of-Phase 2 Meeting, last month; preparing to readout our Phase 2 data for our uremic pruritus program, and then evaluating next steps for that program; and finalizing the protocol for our upcoming Phase 2 trial of Oral CR845. So let me start by generally describing our Phase 3 program for I.V. CR845 in acute pain. And then Joe Stauffer, will then provide details of the upcoming trial. And I'll finish with our uremic pruritus and Oral CR845 programs, before Joe Schoell runs through the numbers and we head to Q&A. Just as a reminder, CR845 is a novel kappa opioid receptor agonist that offers the potential of pain relief without typical opioid side effects. There is currently a significant unmet need in the postoperative pain market setting, where patients are not only dealing with generally and adequate pain treatment post-surgically, but also in real, debilitating adverse events associated with current reliance on traditional new opioid pain medication such as fentanyl and hydrocodone. We believe that CR845 with its unique profile has the ability to provide significant pain relief in this setting, while also significantly reducing the burden of side effects currently experienced by the majority of patients. In April, we held our End-of-Phase 2 Meeting with the FDA…

Thank you, Derek. So as Derek mentioned, our meeting last month with the FDA provided valuable guidance around our whole Phase 3 program for I.V. CR845, and we are currently working with the agency to finalize the protocol for that initial Phase 3 study. Following their review, we believe it will initiate in the third quarter of this year. Additionally and importantly, for our ultimate regulatory submission for the drug, the agency has also acknowledged that it believes that the non-clinical and toxicology packages submitted for I.V. CR845 as well as our CMC strategy are supportive for ultimate NDA submission. Turning to the trials themselves, as Derek discussed, we now anticipate that the first Phase 3 trial will be a randomized double-blind placebo-controlled adaptive design trial in male and female patients, undergoing abdominal laparoscopic surgery, including laparoscopic hysterectomy and other procedures associated with moderate-to-severe postoperative pain. This is very similar to the adaptive surgical trial we discussed with you on our last earnings call at March. CR845 will be administered both pre and postoperatively, with patients assigned to receive one of three doses of I.V. CR845 or placebo. It's clear from our Phase 2 data and laparoscopic hysterectomy that pre and post-surgical dosing for CR845 provides the largest analgesic effect. And speaking as an anesthesiologist, that's how we like to use analgesics, to stay ahead of the pain curve. And the agency has given us their support of this dosing protocol as well. The trial will be designed to accommodate an interim assessment of efficacy and safety across doses by an independent monitoring committee in the first half of 2016, with an adaptation to the optimum doses at this time point. We will then proceed to complete enrollment and readout in 2016. We would currently expect to disclose any dose…

Thanks, Joe. So as you can see, we're very excited about this program and the opportunity it provides to put us in the strongest possible ultimate registration package, while maintaining our data readout timelines and projected cost for the whole program. So we look forward to updating you as our first Phase 3 adaptive trial gets underway, and we will be happy to provide more details about the final study protocol at that time. Now before I turn the call over to Joe Schoell for our financials, I want to touch on other two CR845 clinical development programs. For Oral CR845, as you know, in the fourth quarter of '14, we reported positive topline data from a Phase 1a/1b trial of the tablet formulation of Oral CR845 conducted in approximately 150 healthy volunteers. All tablet strengths tested were safe and well tolerated, and were found to be pharmacologically active, as determined by standard biomarker measurements. We've continued to use this data to inform the design of our first Phase 2 trial in osteoarthritis patients, which we anticipate initiating in the third quarter of this year, with topline data still expected by yearend as we've previously guided. And then finally, we have a emerging clinical program in a non-pain condition, that being uremic pruritus. And just as a reminder, here uremic pruritus is a chronic systemic itch condition that can occur in patients with renal failure, most often seen in patients receiving hemodialysis. There are approximately 400,000 patients in the U.S. and 2.2 million globally undergoing hemodialysis, and it's estimated approximately 50% of these patients suffer from renal or uremic pruritus. Currently there are no approved products in the U.S. or the European Union for that matter for those conditions, which can be quite severe, resistant to treatment with the usual…

Thanks, Derek. Net loss was $4.7 million or $0.21 per basic and diluted share for the first quarter of 2015 compared to a net loss of $3.4 million or $0.22 per basic and diluted share for the same period in 2014. Collaborative revenue was $489,000 for the first quarter of 2015 compared to $151,000 for the same period of 2014, comprising of revenue that had been deferred upon the entry into the license agreement with Maruishi Pharmaceutical Company. Clinical compound revenue was zero for the first quarter of 2015 compared to $27,000 for the same period in 2014, from the sale of clinical compound to Maruishi. Research and development expenses were $3.4 million in the first quarter of 2015 compared to $2.2 million for the same period of 2014. Higher R&D expenses in the first quarter of 2015 were principally due to a net increase in direct preclinical studies and clinical trial costs, an increase in consultant services, in support of preclinical and clinical trials, and increases in payroll, recruiting and related costs, including stock option expense associated with R&D personnel. General and administrative expenses were $1.8 million in the first quarter of 2015 compared to $1.4 million in the same period of 2014. The increase in the first quarter of 2015 was primarily due to increases in professional fees, public investor relations costs, payroll and related costs, mostly due to increases in headcount, and directors' and officers' insurance costs. Interest income was $14,000 for the first quarter of 2015 compared to $22,000 for the same period of 2014. As of March 31, 2015, cash and cash equivalents were $47.4 million, compared to $52.4 million at December 31, 2014. The decrease was principally related to cash and cash equivalents used in operating activities during the first quarter of 2015. Now, we'll turn the call back over to the operator for Q&A. Thank you.

[Operator Instructions] Our first question comes from Annabel Samimy with Stifel.

I just want to clarify with the Phase 3 program, is this a change in the way that FDA is looking at these pain trials now, because initially it's always been about hard tissue and soft tissue trial, and then it seem like adaptive trial design was almost a secondary supportive type of trial for your Phase 3 program. Now, it seems like this is guiding the rest of the year Phase 3 program. So can you just help us understand the shift here with the FDA? And then also with the Oral, you've moving into osteoarthritis, which is seems like a chronic indication and we always saw that the first indication is going to be more acute for like maybe the discharge population. So maybe you can help us understand the change there? Is the Oral more of a proof-of-concept? And how do you get this trial done by the end of the year, if you're starting in the third quarter?

Let me just make a couple of comments, and then I'll turn it to Joe and he can through the details of what you've asked. First of all, in terms of the agencies opinion on the model we use, I think the agency regards us, as you know, as an NCE, a novel class of compounds. They're keen to see additional patient exposures across a broader range of surgeries with this molecule. Also keen to see a range of doses with both pre and post surgical dosing. And so that is really our estimation a way to optimize the doses we're going to use going forward. As we have indicated, we previously guided to multiple doses and multiple models, that really gives us a -- allowing it to streamline the program, select the doses from the first study, and then move smaller amount of doses, optimally one, possibly two into additional models to complete the program. Now, I'll let Joe comment further on that, and then maybe you can handle on the OA.

So the agency still likes the hard tissue soft tissue model and we do too. This particular design we actually submitted to them in anticipation of them looking at something like this. And as Derek said, it does provide us an opportunity to optimize our dosing, not only in women, but in men as well because we're going to be doing other surgical procedures that don't just involve women, that's very helpful to us and helpful to our label ultimately. And it also helps us make smarter decisions about winnowing down certain doses and the minimal effective dose as an example, not only in this trial, but in our other two trials, so that's all very helpful to us and to them to generate data that would instruct the label as we used to say at FDA. On the OA piece, the OA trial is a smaller PK safety tolerability and effectiveness trial. It is not designed to be -- it's not a placebo control trial, its single-blind and open-label, but it helps us get an understanding of the steady state PK in patients. Up until now we haven't had any exposures in patients with our oral drug. We've had very good experience with steady state PK in healthy subjects up to one week, but now we have to go to the next level and put it into sicker patients with osteoarthritis. So in a very stage way, we're going to make sure that PK that we saw, that we like in healthy subjects is same as in patients. We expect it to be the same or similar with a similar safety profile as well. After we get that data in a way, again, with the Oral, we would then look at scoping out an efficacy trial.

And just one another additional point, Annabel, in relation to the patient choice, of course, very much an inflammatory condition, and as you know, CR845 is potently anti-inflammatory unlike standard mu agonist. So we really wanted to select the patient group where we could take advantage and optimize that particular aspect of the pharmacology also.

If I could just ask a follow-up. In this chronic condition OA, are you going to be able to go further with this development program yourself or you're going to have to partner at Ox, this was always a bigger indication for you?

We'd certainly like to take this through the Phase 2 placebo-controlled proof of concept studies, that's always something we've indicated. And then at that point, we'd most likely look for a partner on this particular program.

Our next question comes from Charles Duncan with Piper Jaffray.

My question is related to this adaptive design thing. I know that you haven't fully articulated the protocol, but I'm wondering if that is meant to be, say, an interim look in terms of sizing or is it specifically going to be looking at doses? And I think, Joe, you mentioned an opportunity to focus on our lower dose or higher doses, if necessary?

That's correct. So it actually allows us to do both of what you mentioned. It allows us to optimizes the doses both low and high and it also allows us to size and potentially even drop a treatment arm, if we find during our interim assessments that we find a treatment arm is just not living up to the expectation that we would have, so it allowing you to go up in size is helpful because you want to make sure that you can get to a win in one of those doses. And the other thing is when you can drop a treatment arm, as an example, you can perhaps skinny down your trial and go faster. In other words, you don't have to necessarily carry through all the treatment arms the whole way through, particularly if one doesn't seem to be working as well and that's part of the adaptation. And all that is building to the charter of the protocol that we're working on with the FDA and this is something that this division is open to. I mean, I was at the FDA meeting and those discussions went quite well with them, and so I think they appreciate what we're trying to do here and hopefully that answers your question on those two pieces, sizing and treatment arm.

And also I really like the pre and postoperative treatment paradigm. I think that that will show well for your candidate. But let me ask you about what you anticipate the differences to be with the second, two Phase 3s, one of them is obvious it's a hard tissue bunionectomy, but the other one laparoscopic hysterectomy, I'm kind of wondering why essentially three Phase 3s that are needed, not two?

Well, as we said before in the previous guidance, you only need two trials to win. Many companies have done more than two trials, more shots on goal approach. So we believe that doing these three trials will give us the minimum two that we would need for pivotal efficacy. On your second question about, I think where you might have been going with size of those trials, my anticipation is that the size of those trials gets smaller, because we get smarter about how we optimize our dosing in this current Phase 3 adaptive trial that we're looking at now. That's why we're able to start those later and still finish on time because the full expectation is that they would be smaller trials.

So the timelines for the overall program are pretty much the same. And you mentioned something in your press release, whereby currently proposed trials better position for the strongest possible regulatory submission. A better position versus what? What would the alternative be?

Well, when you can conduct at least two and likely three trials, first of all, it gets you to the sample size that the agency is looking at a number they want an overall 500, not 500 exposures, they want 1,500 exposures. What they really would like to see is most of those exposures in the dosing regimen that you intend to use for your label. And so by doing that you don't have to waste time in some of your other pivotal trials, exploring doses that likely won't be used in your label, either because they are minimum effective dose or they don't work at all.

And really the adaptive trial design is a risk reducer, in terms of --

Correct.

And then, I guess, at this point it's probably too early, but did you get any feedback from the agency in the End-of-Phase 2 Meeting regarding the potential scheduling of the drug or what would be required to show for a positive schedule?

So Charles, we got very positive feedback on our HAL data and we also got constructive feedback on our preclinical package in relation to abuse potential. But as you know, that will be a decision for contemplation at the NDA level. So no firm commitment in terms of scheduling at this point.

Correct.

Our next question comes from Corey Davis with Canaccord.

With respect to the things that you are going to vary on the dosing in the Phase 3 IV, is it a change in the length of time that a patient is exposed to it or is it just a change in the concentration that's in the IV?

Concentration. Sorry about that.

And is it different pre and post-surgery?

No. The dose that we're going to give pre-surgery is the same as the dose we're going to give post-surgery. And then we continue that dosing regimen out in a fixed interval kind of way. So to make it really reflect, what would happen in the real world and also optimize our chance for a win in terms of efficacy. So the agency was actually quite happy and supportive of us pre-dosing this drug. They know that it's got some anti-inflammatory properties, we've always believed that, our current Phase 2 data suggest that as well. And that only make sense in terms of when you're taking care of these kind of patients. So pre-op and post-op dosing continued throughout the dosing scheme is what we're going to do. And it's what we have done in a previous Phase 2 hysterectomy trial at least in one of the arms.

And do they continue to get drug beyond that 24-hour endpoint?

No. They only get drug for 24 hours. We have to observe them though past 24 hours, because typically these patients are in the hospital for at least 24 hours, if not 48 to 72.

And the dosing wouldn't vary based on a type of procedure?

Correct.

And then on the Phase 2 study, it sounds like you're not going to get any real efficacy data at all from that, is that correct?

Well, so if you define efficacy the way I do, which is the need for a placebo, then you are correct. We would not get efficacy, because there is no placebo control or even active control in the dosing regimen. However, we will be getting effectiveness and effectiveness is defined as, are the patients changing their pain scores from the beginning to the end of the trial. This trial will be a short trial. It's only two weeks long. As I said, it's really set up to look PK, safety, tolerability and effectiveness in that order. But it does so, just to understand, so we're really looking at steady state PK as the primary endpoint. And we want to make sure that that we believe that what we saw in our healthy subjects, we see in our chronic pain patients with OA. However, looking at effectiveness though, without a placebo, still does give you a sense of how does the drug perform in those first two weeks of dosing, all right. Our expectation is that patient's pain scores will come down, but they may not. But the point is that we at least get a sense from, say, a patient global or some of the other secondary endpoints that we'll be looking at, as to whether or not there is any type of trend lower in their pain scores, which we do expect to see.

And so Corey, we'll also get the opportunity to directly measure anti-inflammatory biomarkers and so on in these patients. Something we haven't had the opportunity to do in chronic inflammatory pain to this point.

And how many patients would you envision in that Phase 2 and how many different dosing arms?

So right now it's still under discussion with the agency, but it's looking like anywhere between three and four dosing arms. So three and four different doses of drug in anywhere between 60 and 80 patients.

Total?

Total.

And then back to the IV Phase 3 for that first trial, do you know how many patients yet you'd need?

In general, it's going to be anywhere finally between 400 and 600 patients. We're still in negotiations with the agency, but you can expect it to land around that sample size.

And because you said you needed 1,500 total for the whole Phase 3 IV program?

We need 1,500 total for the entire program, but clearly we're not going to get 1,500 patients out of this trial, but with 400 to 600 exposures. And remember some of those exposures are going to be in placebo, so they won't count, but those exposures that we'll get out of this trial will then be added to the current exposures that we already have out of our Phase 2 program as well as our Phase 1 program, and then the additional Phase 3 trials that we'll have to do. And all of those exposures will be wrapped up into this submission and all of that again will be a discussion for the FDA at the pre-NDA meeting. But right now, they have been consistent with what they are looking for 1,500 total exposures.

And the interim analysis, do you know how many patients you need before that interim analysis can take place or is that still under discussion?

It's still under discussion. We have an idea, and I think we're in the right spot with that, but the protocol hasn't been finalized yet with the agency.

And then last question is how are you feeling about the ability to enroll these kinds of patients' competition from other drugs out there, how many centers are you going to need, so some time it can take place quickly?

We'll need more than 10 centers and likely less than a 1,000 centers, but I'm feeling pretty good about it, Corey. It's always one of those things where you won't really know until you get going. We have an idea of how many centers we need and it will be in double-digits, but we also have to keep in mind that keeping those centers to as few as possible to reduce variability amongst the surgeons and surgical technique is something that we pay attention to. But I think it's completely manageable, and in fact a lot of the centers that we used in the past, we'll be going back to, they know us and we know them.

And then sorry, I lied, one more.

All right.

The Phase 2 pruritus study if that doesn't work is there read-through for the pain indications or is it independent mechanisms where you couldn't say one way or another?

We think that's independent, Corey.

Our next question comes from Alan Carr with Needham.

Wondered, if you could clarify a bit about, talking with Corey about size of these trials, 400 to 600 patients for each of the three and you mentioned an additional Phase 3 trial, could you clarify that?

So for this current Phase 3 trial there will be between 400 and 600 patients that we'll have. All of those patients are either going to be on active drug or placebo.

That's the adaptive one.

That's the adaptive trial that we're currently talking about. So I think Corey asked me about how many patients in this trial. So when I said, 400 to 600 patients, I mean, 400 to 600 patients in this adaptive trial. In the other trials that we still are planning for those trials will likely not be that big, they may not have to be that big, because we can optimize, which doses we want to use, it maybe just one or two, in either case we're still able to get ourselves to the overall exposures that we need for the total package.

So those three trials will get you over the 1,500 number. How many have been in Phase 1 and Phase 2, how many exposures do you have?

That's correct. Total exposures is like almost 500, between Phase 1 and Phase 2.

What's left, I guess, in terms of, you mentioned there are till some things to files with the FDA, I guess, could you go over that? And then, for the other Joe, if you could comment on burn and how long do you expect the cash to last?

So one of the things we have to finalize is the charter, so with the Independent Data Monitoring Committee. So that's one of the things we're going to finalize and that's actually going quite well. Other than that some little tweaks here and there on certain entry criteria, enrollment criteria, those types of things, how many patients per site, those are the type of a statistical issues that we have to finalize, but all those are manageable, they just take time to work with the agency.

So it's just details around the interim analysis, so its sounds like is the key.

Yes.

And then, Joe, around burn?

The burn, we're expecting about 15 months.

Our next question comes from Chiara Russo with Janney.

A lot of them have been asked and answered particularly about the study sites. But I was curious about the uremic pruritus. I know that you're currently only looking at it over the course of two weeks. I am curious if further out in the studies, you're going to have to do sort of a longer exposure times, because pruritus I'm assuming is more chronic condition?

We do anticipate we're going to extend those efficacy trials to probably between six and eight weeks based on the guidance the agency has given to other people in this area.

And my second question is do you think that there is the potential for any sort of accelerated programs on the pruritus front?

We believe so. As some of that clinical need, there's nothing improved in the U.S. and that certainly would in our minds qualify as a breakthrough medication.

So with the Phase 3 trials, I'm assuming that you're all going to get them done within the 2016 timeframe. I'm assuming that the gap between data from the first one to the last one its going to be very short, so we kind of want to get a big data dump at the end of the year, do I have sort of that correct?

Correct.

So there is no space there, for instance, to ask whether you could file an NDA with two out of the three, probably you won't do that because the data is going to be so close together.

And the other thing to is that in terms of total patient exposures, if I don't get enough exposures out of two trials, there is no way we're going to go to the agency and have that discussion, because we know what the answer is going to be. So a lot of it just depends upon how many exposures we get out of two trials.

Our next question comes from Ken Trbovich with MLV & Co.

I just wanted to follow-up on the question. I think Charles had asked earlier about the scheduling. As it pertains to how the NDA, I know that the agency wouldn't necessarily give you their feedback at this point, but is it your intention to file it, whether request it not be scheduled or you're going to look at Schedule 4 when you submit it?

No, that's our absolute intent is to submit it requesting non-scheduling. We're not going to request Schedule 4, instead we're going to request non-scheduling. Our anticipation is it will be lower than 4, which then only left is non-scheduling or 5.

So their response to your filing, obviously you can't determine, but your intention is file it as non-scheduled and rely on a preclinical data showing that it doesn't cross the blood-brain barrier and then obviously the HAL data as well?

That's correct.

Absolutely.

And then the elephant in the room that nobody asked, patient exposure, as I know that there is a dose difference for uremic pruritus, and I know we won't know for certain how much more you're going to do in that indication until we see the data later this quarter, but wouldn't you be able to use uremic pruritus patients as part of the 1,500 exposures?

No, you can't. It's a good question though, you can't because there are two different patient populations, there are two different dosing regimens, there are two different divisions at the FDA, and there are two completely different indications.

So even though it's the same chemical entity?

Correct.

So when we think about it from a safety standpoint, will the FDA look at it separately from that standpoint as well? So in another words, if there were safety, it is a sicker patient population, so we'd expect to see some of those patients both on placebo and active having serious adverse events, in some ways it may not be drug related, but I'm assuming then that safety database is somewhat viewed the same way or no?

The way you're thinking about it I know makes all kinds of common sense, Ken. But from an FDA perspective, these discussions have really never come up since I've been here at the company about mixing these two databases. Safety is a relevant term, right. It's relative to the types of patients that you're using it, and the way you're dosing it. And so there are two completely, as I said, different patient populations, one patient population is chronic, they're getting it three days a week and their kidney's don't work. And in the case of surgical patients, they're getting a dosing regimen over 24 hours, and then they are out of the hospital. So I can see where you're going, but as I said two different divisions at the agency, two different indications, two different NDAs.

You reason it in terms of safety, of course, because these are, as Joe indicated the sickest of the sick patients, and as you know we're exposing these people to essentially two weeks worth of constant exposure to our drug, and to date we haven't seen any serious adverse events, and certainly haven't seen any CNS issues with these patients. So for us with the HAL study, we are pretty much conforming, we don't have any CNS liability with the drug as we've seen with previous, what we like to call, first generation kappa molecule. So that data is really conforming safety for us, but Joe's point, as I said for IND and to that point we haven't mixed and matched our INDs in terms of safety numbers.

And so they're looking it is completely separate patient population as well then?

Correct.

And then, I guess, Josef, for the financials. Can you break out at all how much of sort of the planned revenue or the revenue that was reported in the quarter, I know you mentioned none of it was clinical compound. Was any of it related to the Maruishi milestone that was -- the triggering milestone, I think you guys have discussed before how much of that was recognized in the first quarter?

So there was no milestone recognized in the first quarter. We would have indicated that the revenue that we did have in the first quarter related to strictly the deferred revenue from the initial licensing transaction not milestones. And we had no compounds sales this quarter.

So then the $2 million -- the milestone that's going to be earned when they begin the study, can you give us some guidance on recognition?

It looks like probably the third quarter.

That study will initiate, Ken, at the completion of our proof-of-concept trial, so we anticipate later this year.

But you expect it all be recognized in the single period, you're supposed to spread out of multiple periods?

Yes.

Our next question comes from Jim Molloy with Laidlaw.

The Phase 3 trials that you're running, when you switch the abdominal surgery go first and obviously the bunionectomy and hysterectomy are following, the adaptive trial design informing that. And is that a significant savings in money as well with the potential smaller trial size?

Approximately same cost.

It's about the same costs. It's just a matter of slight timing. The overall Phase 3 program cost is still the same.

And did you, I would guess, you said what the ultimate cost with all three of these trials likely will be?

No, we have not.

Will you?

[Multiple Speakers] we make presumptions on runway and cash burn, but not individual trial cost.

Now, as we're looking at these trial, I mean, obviously this is quite a change, last it was going to start second quarter, now it's starting in '16 with the laparoscopic starting here in the third quarter on target. At what point, if now start looking in, when can we have an idea that are these are on track? And you'll still hit the end of '16, will there be data points along the way, where we'll be able to know that things are remaining on track?

We are certainly going to guide when we start this first trial, and we're also going provide a little more detail after the FDA has confirmed the protocol we submitted. And we're probably going to guide, although not with efficacy data, but we're going to guide at the interim point, and that's first trial also.

And then last question on the pruritus indication or what are the next steps after this Phase 2 data? And I'm assuming, I guess if its two week trial, the final patient must be coming in any day now. Is a that fair assumption? And the next steps for End-of-Phase 2 Meeting or start of Phase 3, what's your thoughts on timing there?

Yes. You're right on that Jim. I think the next step is if the trials is post, as we hope, then we would get down to the agency and look for guidance on how to move fast that to registration.

Just to be clear, something like that could happen in '15 or we're looking in second half of '16 for start on this one?

Well, I'm always not to keen to predict timelines as it comes with the FDA restrictions on those. But as soon as we have the data on this we will request a meeting with the agency, and look in for guidance that how we can move that to registration.

And I'm not showing any further questions at this time. I'd like to turn the conference back over to our host. End of Q&A

Thank you, everybody. Thanks for participating on today's call. And we look forward to updating you very soon, as we start our first trial. Thank you.