Good afternoon, welcome to Cara Therapeutics First Quarter 2017 Financial Results Conference Call. 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 Michael Schaffzin with Stern, Investor Relations. And welcome to Cara Therapeutics first quarter 2017 financial results conference call. A news release with our first quarter financial results and corporate update became available just after 4:00 PM today and can be found on our website at www.caratherapeutics.com. You may also listen to 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 announced of our ongoing and planned clinical trials, the expecting timing of our planned clinical trial, the results of our ongoing and planned clinical trials, the potential for CR845 to be a therapeutic option in multiple pruritus indications, future regulatory and development milestones for our product candidates, the size of market are potentially addressable by our product candidates and are expected to cause risks. 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 the company's filings with the Securities and Exchange Commission, including the Risk Factor section of the company's annual report on Form 10-K for the year ended December 31, 2016 and its other documents subsequently filled with or furnished to the SEC. 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 whether as a result of new information, future events or otherwise except required by law. Now, let me turn the call over to Cara President and CEO, Dr. Derek Chalmers.

Thank you, Michael. Good afternoon everybody and thanks for being with us today on the call. I'm joined by our Chief Medical Officer, Dr. Joe Stauffer; and our Chief Financial Officer, Joe Schoell. So, the first quarter has been certainly very productive for us with significant progress for our lead development candidates CR845 currently being evaluated in multiple pain and pruritus indications. Most notably, we reported positive top line data from Part A of our CKD associated pruritus trial in hemodialysis patients supporting CR845's potential as a chronic therapy for patients with this condition. After this data readout we strengthened our balance sheet with a successful follow-on offering which raised more than $86 million in net proceeds providing us with a projected financial resources required to advance our clinical plans for both IV and oral CR845 through multiple data readouts. Additionally, we recently reported positive respiratory data from our Phase 1 safety study observing the I.V. CR845 did not significantly differ from placebo across three quantitative measures of respiratory safety and healthy individuals. We believe that further differentiates CR845 safety profile from traditional mu-opioids which are of course linked directly to respiratory depression. Finally, enrolment is now complete in our Phase 2b trial of oral CR845 for chronic pain and we continue to enrol our adoptive Phase 3 trial of I.V. CR845 in patients for the acute post-operative pain and we expect of announcements on both of these trials during the second quarter. So now let me start with an overall summary of data from our pruritus program before passing the call to Joe, who'll take you through progress in our other clinical programs. So as we've discussed previously and as a reminder (CKD)-associated pruritus is an attractable systemic itch condition affecting approximately 60% of dialysis patients with end stage…

Thank you Derek. As highlighted we're very pleased with the pruritus data and our continued clinical execution across all programs during the quarter. Looking forward, we expect results from both our interim assessment in our Phase 3 trial of I.V. CR845 in acute post-operative pain and our Phase 2b trial of oral CR845 in chronic osteoarthritis pain. So starting with our oral CR845 Phase 2b trial. I'm very pleased to announce that this trial is now fully enroled at 480 patients and on track for data readout later in Q2. As a reminder, this is a double-blind placebo controlled multiple dose Phase 2b design testing three tablets strength of CR845 dosed priced daily over an eight-week period treatment in patients with moderate-to-severe pain. The trial design incorporates a four-week titration period for a response followed by four-week maintenance period. The primary endpoint will be different from baseline and pain scores in CR845 treated patients versus placebo at the end of eight-week treatment period. Secondary endpoints include the change from baseline in the Western Ontario and McMaster Osteoarthritis Index and now the rescue medication use in the Patient Global Assessment or PGA of osteoarthritis. Now moving onto our adaptive pivotal clinical 3001 trial of I.V CR845 in post-operative pain. This is a three-arm trial testing 1 and 0.5 micrograms per kilogram of CR845 versus placebo and up to 450 patients undergoing various abdominal surgeries. The trial design accommodates an interim assessment for conditional power across doses at approximately 65% enrolment with an adaptation to optimum dose in subsequent progression to complete enrolment. The result of this analysis will determine the timing of top line data from this trial. I'm pleased to announce today that we passed the enrolment threshold for our interim assessment and expect to complete this analysis next month.…

As a reminder the full financial results for the first quarter can also be found in press release issued today after the market closed. We reported a net loss of $22.2 million or $0.81 per basic and diluted share for the first quarter of 2017 compared to a net loss of $10.7 million or $0.39 per basic and diluted share for the same period of 2016. We reported revenue in the first quarter of 2017 of $843,000 in connection with the sub-license by Maruishi of our intellectual property related to CR845 for use in patients with uremic pruritus in Japan. Off that amount, $530,000 was recognized as milestone and license fee revenue and $313,000 was collaborative revenue. In addition, the company recognized $68,000 and $7,000 from the sale of clinical compound to Maruishi during the first quarters of 2017 and 2016 respectively. R&D expenses were $20.8 million in the first quarter of 2017 compared to $8.5 million in the same period of 2016. The higher R&D expenses in the first quarter of 2017 were principally due to a net increase in direct clinical trial cost and an increase in payroll and related cost for R&D personnel. General and administrative expenses were $2.4 million in both the first quarter of 2017 and 2016. Representing decreases in professional fees and public investor relation cost and depreciation, amortization expense which were offset by increases in stock-based compensation and payroll and related costs. Other income was $90,000 in the first quarter of 2017 compared to $149,000 in the first quarter of 2016. The decrease in 2017 was primarily due to lower dividend income earned on a lower average balance of our portfolio of investments. As of March 31, 2017 cash and cash equivalents and marketable securities totaled $36.8 million compared to $58.3 million at December 31, 2016. The decrease in the balance of cash and cash equivalent and marketable securities primarily resulted from the cash used in operations of $21.6 million. In April, 2017 the company completed a public offering of 5,117,500 shares of its common stock including full exercise of the underwriters option to purchase additional shares at $18 per share. Raising approximately $86.5 million in net proceeds after deducting underwriting discounts and commissions, but before deducting estimated offering expenses payable by the company. Turning to our financial expectations, based on timing expectations and projected costs for current clinical development plans Cara expects its existing cash, cash equivalent and available for sale marketable securities will be sufficient for the company to fund its operating expenses and capital expenditure requirements into 2019, without giving effect to any potential milestone payments under existing collaborations. And now I'll turn it back to the operator for Q&A.

[Operator Instructions] our first question comes from Charles Duncan of Piper Jaffray. Your line is now open.

First of all, thanks for taking my questions and secondarily congrats on the quarter, good progress in the quarter. I had just a couple of questions I believe you were planning to request a meeting with the FDA regarding the uremic pruritus program and I'm wondering if you've requested it and if you could provide any color on timing there.

Yes, so we're Charles as we said before and we will be requesting that soon and our plan is to have an end of Phase 2 meeting with the FDA and finalizing the dose we're going to take forward into our Phase 3 registration trial for uremic pruritus.

Okay and any sense of when you would be requesting that, it's that roughly mid-year or [indiscernible]?

No we will be requesting that, this quarter and our aim is to have that meeting most likely Q3.

As soon as we can, it just all depends on the schedule but it would be reasonable to expect that it can be Q3.

There is no gating events from your perspective at this point.

No, I mean it's just tallying up all the final data and getting a package in front of them.

Okay and then regarding the Phase 3 interim for the acute pain indication. I guess I'm kind of wondering if you could provide us a little bit more information on what you would be or what you think that you'll be able to talk about in that upcoming press release and then I'm also wondering with the bolstered balance sheet, if it's just prudent to assume that trial is going to be expanded just to reduce potential effective noise in the data.

Sure, so it's a good question. I mean there is really a couple outcomes that could happen with this trial and of course that data will drive the press release, but we can either continue both doses for enrolment, we could drop a dose and continue enrolment or possible we coupled stop for early efficacy and really any of those three are possible, we're still blinded so we just have to wait and see, what it looks like now. We have independent data monitoring committee that sees this data first. They look at the data not only for efficacy but also for safety and will make a recommendation to us and then we'll follow that accordingly.

And Joe would you be able to talk about the number of patients that you would expand the trial [indiscernible] your or give us some sense of that?

Sure, I mean so our target right now is about 125 per arm which we stated before, now we specified that we can go up to 150 per arm, but the [indiscernible] will tell us how high we could go, if indeed we needed to go little higher so maybe sometimes we do that, it really all just depends. I wish I could had a crystal ball and tell you exactly what it looks like, but until it's unblended that's when we will know. And of course we have to make any of those changes, we'll make [indiscernible] .gov as well and we'll have to tell our investigators. But for right now, we can jump to 450 total.

But the point, you've done all that math up front and so you have a pretty good sense of what the scenarios, are right?

Correct, it all depends on the conditional power.

Okay, very good. Thanks for taking my questions.

You're welcome.

Thank you. Our next question comes from the line of Annabel Samimy of Stifel. Your line is now open.

This is Esther Hong in for Annabel. Just a couple of questions, first I wanted to drill down on the specific PK issues that you're looking for as you develop oral CR845 in the hemodialysis study for UP and then how translatable is that for potentially bringing oral CR845 for pre-dialysis setting which would obviously be an excellent expansion opportunity. Because presumably the pre-dialysis patients are not as renally [ph] comprised so is there anything else that might affect the PK between the two populations.

Sure so the two populations are absolutely different and they are absolutely the same, right. They both have kidney disease, however one requires dialysis and the other doesn't and so, what we see in the hemodialysis patients orally may or may not be what we see and someone could say, who takes the drug orally as an outpatient not on hemodialysis and the data will tell us what the best way for it is. Remember that all these patients whether they're on dialysis or not they have other issues, multiple other medical issues beyond just having end-stage renal disease, they have gastroparesis, obesity hypertension, they are on many, many other drugs not that necessarily affects our drugs PK as you know we're synthetic drug and we're not metabolized, but we're renally [ph] extreme and so one of the things, many other things we're looking for is just an overall safety profile tolerability profile between the two groups whether or not indeed there is a difference in how, an outpatient taking it orally not on dialysis would handle it and in terms of linearity for instance or is there any dose or is there any drug accumulation in that patient versus a hemodialysis patient. So those are all the things that are on the table that we're going to make sure we get a handle on, at this type.

And just to extend that little bit, where we are, we have just completed the end subject portion looking at the PK using oral tablets in hemodialysis patients, we will also be looking in CKD patients non-HD a little later this year also and obviously that allows us to directly, empirically measure what tablet strengths are appropriate based on the stage of kidney disease, so that's the main aim here to make sure and obviously we have exposure from our I.V. experience we can model as being efficacious so we can absolutely define which tablet strengths that are appropriate for each stage, that are in terms of CKD patient.

Okay, great and then OA side of oral CR845, so if pain release can be established from the I.V. trial in the post-surgical pain program, what do you expect requirements will be from a development perspective for the oral drug for OA? So obviously long-term safety is required but how many Phase 3 studies would you need, what would a development program look forward in OA?

Sure, so in a way it's a relatively straight forward. I mean if this trial is positive for us, we'll go, we'll have a mean with the FDA and into Phase 2 meeting, it's very, very likely that they would ask for two, 12-week long trials each of them placebo controlled, they would also ask for 52-week safety data that would follow ICH guidelines. So the 52-week safety data is open label.

Okay and then last question, with proceeds from the secondary which development programs will Cara get through?

And we've outlined this publicly, so we would be complete our IV program in post-op pain, our I.V. CR845 program in uremic pruritus and hemodialysis patients and finish the current oral program which Joe's just outlined in terms of oral Phase 2b study in osteoarthritis patients. Also within the context that raise, we're going to look and we've said that's in our guidance, we're going to move the on CKD associated pruritus and look at proof-of-concept and other conditions where we see pruritus as an attractable unmet need in the first of these is likely to be liver associated pruritus and there we would aim to initiate our Phase 2 proof-of-concept trial a little later in 2017 and not particular condition.

Okay, great. Congratulations on everything.

Thank you very much.

Thank you. Our next question comes from the line of Alan Carr, Needham & Company. Your line is now open.

Can you, I guess give us a big picture of your strategy around the other pruritus indications? Well you mentioned chronic liver disease something you look at later this year, but where do you take this drug in both I.V. and oral formulations beyond uremic pruritus in the hemodialysis patients.

That's a great question. And I think we said that's probably we think by virtue of the mechanism here which is, if you like at the end of [indiscernible] pathway actually on the C-fiber and block the release of pruritogenic substances from immune cells directly in the dermis [ph] that should be applicable across disease state. So obviously we want to move into CKD non-HD since we think that path of physiology responds well to kappa agonist beyond that liver as you know we've seen proof-of-concept from the Japanese drug [indiscernible], which just had a label expansion in Japan and older if you like first generation kappa CNS active certainly not as selective as our molecule but seems to be efficacious there, so that seems like an obvious population to move into. And then beyond that, there is some early evidence with perhaps some non-selective kappas that atopic dermatitis and some other dermatological conditions [indiscernible] not somewhere we may be interested to move to after liver disease in terms of early trials to look at possible efficacy. So those are the three main populations CKD, chronic liver disease associated pruritus and dermatological conditions. And as you know and as we said probably that's the very large patient population large opportunity across there.

All right and then, Joe that you reached the 65% enrolment in the post-surgical pain trial. For the interim assessment are you continuing to enrol that or do you pause until after, you have a chance to look at the data, how does that work?

Good question. We're continuing to enrol and so there is no pause, we continue to enrol because we know that we're going to need more patients at least 375 and maybe more, so you don't want to lose steam while you're kind of taking a pause here and looking so, we are willing and will take a look at the data as soon as we can and let you guys know and make our adjustments from there.

All right and then the last one around burn. I think on the last call, Joe you mentioned that it was a bit front loaded this year, can you comment on how this is going to, the spend will play out this year maybe you can characterize the pattern. You mentioned going to into 2019, but you will have presumably more trial starting up. I know you're at some now, how do we reconcile all that?

I think the start-up of the trials will be later on the in the year probably Q1 and Q2 were the peaks for this year and then 2018 we'll certainly pick back up with the other trials.

So presumably this 52-week trial that you all are contemplating isn't going to be dead [ph]. The uremic pruritus.

Open label 52-week.

Yes, so that one is not going to be that expensive.

It's not very expensive.

Okay, great. Thanks for taking my questions.

Thank you. Our next question comes from the line of Arlinda Lee of Canaccord. Your line is now open.

I wanted to maybe talk a little bit more about this conditional power analysis. What I guess information on early sides of efficacy are likely to see this quarter or is it just going to be a - we decided to x going forward.

Right, so the analysis is based on actually an un-blinding by our data monitoring committee, so they actually unblind the trial and look at it and they tell us what they see, now they're not going to tell us all the gory details of what they see because the way the charter is written, they only tell us whether or not I use the term horse power a lot, like the conditional power. They tell us whether or not, it appears that we're on the right track for what our assumptions were in terms of the original sample size. And so, it's called a Phase 2, 3 adaptive design trial for that reason. So based upon what they see, they tell us and make recommendation as to whether or not, it appears that what our original plan was 125 per arm it seems to be appropriate and if it is, we'll continue to enrol targeting that rate. If it doesn't seem that we have enough horse power based on a conditional power then they do calculations and spreads and tell us, what are the various options that would be for us to increase the sample size and or drop a treatment on, as an example. Right, so there is all kinds of options that we build into this by design, so we can just be smart or try to be smart about the next step after we've taken a look.

Okay and 55%, is 55% of the original 125 or the maximum 150 and is there, chance that you might give or expand it further, if necessary.

We can extend it up to 150 per arm, if we have to go beyond that's probably going require discussion with the FDA, but it all depends upon how many more we might need. I hope that we don't need much more than that, but if we do and if it is not that much more and again, that's the, the FDA is involved in this process as well, right? This is a three-way process between us, the data monitoring committee as well as the FDA.

Okay and then I guess in terms of other itching indications. I think that's a really interesting thing going after additional indication. Are you - how much of these additional indications depends on what we might see with the oral, can you move forward with the I.V. to begin with and then switch over to the oral with, maybe more [indiscernible] to whatever the setting is?

The indications, what the hemodialysis population are going to be predominantly oral and we're looking at a couple of different formulations in that regard. There are also possibilities for other types of formulations and maybe applicable there longer term for life cycle. With the hemodialysis population initially we're going to be looking at oral for these other clinical indications.

Okay, great. Thanks very much.

Thank you. Our next question comes from the line of Ken Trbovich of Janney. Your line is now open.

Just picking up on Arlinda's question. If you could, I guess Joe go back and maybe give us a sense, I know you said one option worth the possibility that you'd stop the trial all together due to efficacy, should we assume that would only be looking at the primary measure in terms of pain reduction or are you guys interesting in also seeing secondary measures like reduction in opioid usage coming out of the study.

Actually I'm interested in opioid usage, I'm more interested in nausea and vomiting, as is the FDA. In fact opioid usage reduction is important but I don't think it's important enough if you don't have any changes. Let's say in nausea, vomiting right so. The way the trial are set up, it's pain have to work first, the secondary endpoint that we specify it's post-operative nausea and vomiting that the scale that we used, we also look at safety and we will look at opioid sparing effects a well. But all those two pieces are really building what's important the clinical relevance of what we see with the conditional power.

Okay and then just with regard to the uremic pruritus program. I guess the idea here that you guys are talking about having trial sufficient to finish let's say three, does that mean that you folks think you're in position style on both UP and I.V. form for both UP and pain in 2019.

Well we're certainly in the position to complete both those program. Ken we haven't absolutely gated on the timing of filing the NDA, but it's obviously as soon as we finish those Phase 3's, we'd love to file the NDAs as quickly as we could.

Sure, so depending on how late in the year, that sort of thing.

Yes exactly.

Okay and then just with regard to UP and obviously the fact that you've gotten oral PK study in UP patients. I'm sorry I guess dialysis patient specifically. I guess one of questions that it raises is, whether or not part of your planning for the Phase 3 would include the possibility of only moving forward with one formulation either oral or IV.

No, so plans [indiscernible] we're going to move forward with the I.V. for UP and hemodialysis patients that's our main focus. The idea of using the oral is to provide some optionality, so but primarily we're interested in the oral to walk us back into CKD patients non-hemodialysis.

Okay. And then just last question on the OA as we think about pace of enrolment for the trial that you're just now wrapping up, is there anything from a learned experience that perhaps we should be thinking of as you prepared to look at this data and looking at the possibility of multiple Phase 3, did the enrolment go easier more difficult sort of how would you characterize that process?

That's two question. I think this enrolment went well and better than expected. These trials are always difficult to enrol than general pain trials. Clearly OA enroled faster generally done than I.V. if patients like what they're hearing about the pharmacology they like what they're hearing about the side effect profile or lack of a side effect profile and the safety profile. I think that helped us a lot when it came to enrolling. Twice a day oral treatment chronically is something chronic pain patients are kind of used to and so made me pretty excited the way it went down and now it's just about wrapping it up and filling the data, out as fast as we can.

Got it and Derek just from a pure development standpoint. Are you guys sort of leaning more towards trying to complete those later studies completely on our own or would you consider [indiscernible] prospect partner following the Phase 2 results?

Now that's a great question Ken. As you know we've always had the view, we want to retain US rights on all our main programs, but if there is an opportunity for an Ex-US partnership under the appropriate conditions of course then that's something we're certainly going to look at.

Okay, terrific. Thank you.

Thank you. Our next question comes from the line of Chiara Russo of Cantor. Your line is now open.

Congrats on the first part of the second quarter and all of the positive data. Just a couple of questions obviously kind of at the end of the call here. And just quickly on the I.V., UP obviously that's going to be administered in a dialysis center. I was wondering if you could sort of give us a little bit more color on how you expect to sort of navigate that bundled payments system with the I.V. formulation?

Chiara thanks. So as we've discussed before, I think on this call a couple of times. Our view at [indiscernible] that we can see reimbursement out with the bundle with the I.V. CR845 approach and the precedent we often say there is as you know, there is room within that legislation for novel I.V. products to be priced at with the bundle if the improved quality of care for those patients and the precedent there recently that we've cited before probably as the Amgen perceived as I.V. molecule which recently granted pricing out with the bundle by CMS and really as a drug that somewhat analogous to ours, it's still three times a week post-dialysis has a metabolic profile that's not excreted in those patients very similar to CR845 and their main argument with CMS was improved patient compliance for that particular [indiscernible] and clearly we have the same argument and perhaps a stronger argument and that there are no alternatives as you've seen from our recent Phase 2/3 data where we allowed so called anti-periodic medications in our patients, in our trial which were really uneffective. So there are no alternatives for CR845 it does allow obviously a higher degree of patient compliance and more importantly an effect of therapeutic for that particular condition. So we think we have a strong case now that there is a precedent there at CMS, we aim to press that case and our view as we can see reimbursement with the bundle.

Are there any other anti-periodics outside of the bundle currently or would be the first?

No there is no currently periodic effect, so if you look at the functional category within that legislation. The anti-periodic are predominantly antihistamines and corticosteroids, so these are clearly not effect. So now there isn't because there is essentially nothing effective in those patients.

Okay and then with the respiratory study, I thought that data was obviously quite powerful. How do you plan on leveraging that data going forward, do you think that something that, it's going to be labelled specific obviously you can kind of augment jump [ph] profile which is sort of your thought on that?

Thank you Chiara. We're really excited about it too. It kind of guarded what we've always believed about pharmacology. This is a kappa drug, it's not on the opioid drug and so even if got into the CMS, it wouldn't cause respiratory depression anyway, this just proves the point. And it was also pretty exciting, we were invited as an oral presentation there were over 1,000 abstract submitted to the ASA. We were one of only eight that were actually invited for this oral presentation and it actually invited us, they actually submitted for manuscript already. So that doesn't happen to often and it's not my experience with the anaesthesiology journal and I think that just speaks to the nature of the pharmacology and the safety story around it. It clearly validates what we believe, the strength [indiscernible] pharmacology and the product and also how people would use it perioperatively. I think that's really important that, we're dosing this drug right now preop right, before patients even wearing oxygen and so it's safe there and we gave it at five extra dose. Right so and one extra dose too. So again we'll leverage that, it's important for us and I think it's important just another good rounding for the story, but I think it also helps us in terms of scheduling down the road as well, scheduling of course is usually related to abuse liability which we've got I think a good story there, with even abuse liability trial, but this is just more icing on the cake there.

Yes, I tend to agree with you there, Joe. And lastly, I know you've got your symposium coming up I think in two weeks on the UP. Any sort of preview, are we going to talk about uremic pruritus perhaps in the stage four, five kidney disease patients kind of what should we expect going into that?

So Joe can answer this in more detail, but Chiara really the aim there is to provide some for like end-users, so these are some of the best known nephrologist in the US and one particular specialist on uremic pruritus and get their opinion on the aspects of this condition, the seriousness of this condition, the lack of effect of therapeutics current standard of care and allow people to question these nephrologist, on how the effect of and the advantageous supports we have here with this particular molecule, so it's really a clinically focused event allow end users to comment on CR845 and effectiveness there.

I mean these are nephrologist, who are in trenches treating patients every day and they're seeing these problems every day and that's why we want to put them in front you, so you can hear it from them, what they're dealing with and you know not just the patient in hemodialysis, but also patients that are having failing kidneys prior to coming to dialysis, I think that's important to hear from them about how they deal with those patients in their itching, in their pruritus.

Awesome. Now that sounds interesting and I look forward to attending. Thank you guys so much for the call and good quarter.

Thank you. Our next question comes from the line of [indiscernible]. Your line is now open.

Thanks for taking the questions. Most questions were answered. But quickly I was just wondering is it fair to say that the receptor occupancy levels that we're seeing in the I.V. CR845 for UP should be a good read through for the post-op pain coming up?

Absolutely and pharmacologically you're correct. So the concentration in blood are exactly the same and obviously we've added the administration so it's freely available and we'd expect similar levels of receptors occupancy in both patient populations.

Okay, great and then quickly just one last one here, that quantitative Phase 1 respiratory data that just came out why did you guys look at the, I think you mentioned in the prepared remarks but the 5 microgram, kilogram and was that planned to help before the clinical hold happened in the first quarter or?

No it actually was planned out after and that's five times what we believe to be an analgesic dosage, just so put some color on that right. Let's say analgesic dose of I.V. morphine is maybe say 10 milligrams I.V., right I.V. push you're coming into the recovery room and you give somebody that kind of dose of drug and maybe a patient would get some pain relief, maybe they wouldn't, maybe they get nauseated, maybe they don't. imagine giving someone 50 milligrams of morphine I.V. push right that's a pretty big, big dose right five times that dose and that's a dose that will probably get you bypassed to acknowledge you in vomiting and getting you into things like maybe respiratory depression or apenea right. So we're trying to choose doses that are meaningful. Obviously the meaningful dose, the dose 1 microgram per kilogram and then some x beyond that. We've even done as you know in the human abuse liability trial from years ago, we had 15 micrograms per kilogram as an I.V. push again that trial was not designed as a respiratory safety trial, it was designed as a human abuse liability trial, but even in that trial there is no hints of any respiratory safety problems. So you just have to pick a dosage, it's nothing that the FDA requires but it's something that we wanted to have, I'm pretty proud of it actually because it's got the attention of the American Society of Anaesthesiologist and I think that's evidenced by the fact of that early request for manuscript and we put on their oral panel.

Okay, great. That's it from me and thanks for the question and congrats on the progress.

Thank you. I'm showing no further questions at this time. I'd hand the call back over to Derek Chalmers for any closing remarks.

Great, thank you everybody for participating today and we look forward to updating your very soon this quarter. Thank you very much. Have a good day.

Ladies and gentlemen, thank you for participating in today's conference. That does conclude today's program. You all disconnect. Everyone have a great day.