Tvardi Therapeutics Inc (TVRD) 2014 Q4 法說會逐字稿

Good afternoon and welcome to Cara Therapeutics' fourth-quarter and year-end 2014 conference call. (Operator Instructions) 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. Welcome to Cara Therapeutics' fourth-quarter and year-end 2014 conference call. The news release with our fourth-quarter and full-year financial results and corporate update became available at 4:00 PM today and can be found on our website atwww.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 include statements concerning the expected timing for the Company's clinical trials, statements concerning the potential results of planned clinical trials, and future development milestones for the Company's product candidates. 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 filed 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 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 are made.

Now let me turn the call over to Cara President and CEO, Dr. Derek Chalmers.

Thanks, Jesse. Good afternoon, everyone. Thanks for joining us on the call this afternoon. I am joined today by our Chief Financial Officer, Joe Schoell, and our Chief Medical Officer, Dr. Joseph Stauffer.

2014 was certainly an important year for us here at Cara Therapeutics, starting with our successful IPO in January of last year and including several significant data readouts throughout the year, as we continue to execute on our clinical development plans for our lead peripheral analgesic CR845. So this afternoon we plan to briefly summarize important development milestones achieved in 2014, clinical plans and readouts for the rest of 2015, and then we will run through the financials and end with the Q&A session.

To start with let me highlight what we consider to be a very important clinical data set from our human abuse potential clinical trial we reported in the fourth quarter of 2014. This trial, designed in consultation with the FDA and their Controlled Substance staff, tested the abuse potential of intravenous CR845 administered as a bolus against a comparator Schedule IV opioid, as measured across a range of validated objective scales in non-addicted poly-drug abusers.

Data from this trial unequivocally confirmed that I.V. CR845 offered a significantly lower abuse potential than the standard Schedule IV comparator. It also reinforced our general therapeutic approach here; that is, by selectively targeting peripheral kappa opioid receptors we can avoid the undesirable side effects, including euphoria and abusability, associated with currently available pain therapeutics. This will be an important differentiating factor for both our intravenous and oral formulations of CR845 moving forward.

With regard to our lead program for intravenous CR845 in acute pain, in 2014 we completed all the necessary CMC work to enable initiation of Phase 3 trials in the first half of this year, upon the completion of our end of Phase 2 meeting with the FDA, which is presently scheduled during the second quarter of this year. We currently plan to conduct three Phase 3 trials, which we believe will provide the breadth of patients and surgical exposures as well as the necessary number of drug exposures to enable a successful NDA review process.

Let me now turn the call over to Cara's CMO, Dr. Joe Stauffer, to run through the main elements of our proposed Phase 3 trial designs.

Thank you, Derek. These planned Phase 3 trials for I.V. CR845 will be similar in design to our completed Phase 2 clinical trials in terms of both type of surgical model employed and clinical endpoints. I should also add that trials conducted by other companies in recent years for FDA-approved acute pain drugs have run similar Phase 3 development programs in soft and hard tissue models using the same primary endpoints. So while of course our final protocols will depend on our meeting coming up with the Agency, there is certainly a precedent for this path.

The first trial we expect to be randomized, double-blind, placebo-controlled in approximately 400 male and female patients with postoperative pain after bunionectomy surgery, the hard tissue model which was used in one of our successful Phase 2 trials. The patients will be assigned to receive one of three doses of intravenous CR845, or placebo.

The primary efficacy endpoint of the trial is expected to be the SPID, or the Sum of Pain Intensity Differences, at 48 hours. Secondary endpoints will likely include rescue medication; morphine use; SPID at other time points; TOPAR, which stands for Total Pain Relief, at 24 hours; and occurrence of nausea and vomiting.

The second trial is expected to be a randomized, double-blind, placebo-controlled trial in approximately 400 female patients with postoperative pain after laparoscopic-assisted hysterectomy, a soft tissue model which was also used in one of our successful Phase 2 trials. The patients will be assigned to receive one of three doses of intravenous CR845, or placebo, administered preoperatively and postoperatively.

The primary efficacy endpoint of the trial is expected to be the SPID at 24 hours. Secondary endpoints will likely include morphine use; SPID at other time points; TOPAR at 24 and 48 hours; and occurrence of nausea and vomiting.

The third Phase 3 trial is expected to be a randomized, double-blind, placebo-controlled adaptive design trial in approximately 500 to 600 male and female patients with postoperative pain after laparoscopic-assisted abdominal surgery, another soft tissue model. The patients will be assigned to receive one of three doses of I.V. CR845, or placebo, administered preoperatively and postoperatively.

The primary efficacy endpoint of the trial is expected to be the SPID at 24 hours. Secondary endpoints will likely include morphine use; SPID at other time points; TOPAR at 24 and 48 hours; and occurrence of nausea and vomiting.

We expect to initiate the first of these trials in the second quarter of 2015, following our meeting with the FDA, and the other two trials in the second half of 2015, with data readouts coming in 2016 to enable NDA submission as soon as possible thereafter. Now I'd like to turn it back to Dr. Chalmers.

Thank you, Joe. In addition to our I.V. CR845 program for acute pain, we've also made considerable progress through 2014 in both our oral CR845 program for acute and chronic pain as well as completing the necessary regulatory and clinical groundwork to enable testing of CR845 as a potential novel antipruritic agent. Let me walk you through both of those programs now in summary.

For our oral CR845 program, in the fourth quarter of 2014 we reported top-line data from a Phase 1a/1b trial of the tablet formulation of oral CR845 conducted in approximately 150 healthy volunteers. This trial assessed six tablet strengths of CR845 ranging from 0.1 mg to 10 mg after single-dose administration, as well as three tablets strengths ranging from 0.1 mg to 5 mg after BID dosing over a one-week dosing period. All tablet strengths were safe and well tolerated, with no SAEs reported after either single- or multiple-dose administration. Moreover, all tablet strengths were confirmed to be pharmacologically active, as confirmed by standard biomarker measurement.

Tablet strengths resulting in plasma exposures analogous to those used in successful post-op pain Phase 2 trials with intravenous CR845 have been identified. This data along with our PK data from this trial will inform the design of our first Phase 3 trial with oral CR845, which we aim to initiate in the second quarter of this year, with data readouts around the end of this year.

We believe the potential of oral CR845 to address significant unmet medical need for a safe alternative to opioids, NSAIDs, and anticonvulsant agents for the treatment of acute and chronic pain is currently significant.

Now I'd like to turn to our emerging clinical program in a non-pain condition, and that is uremic pruritis. This is a chronic systemic itch condition that can occur in patients with renal failure; it is most often seen in patients receiving hemodialysis.

There are over 400,000 patient in the US and 2.2 million globally undergoing hemodialysis, and it's estimated that approximately 50% of those patients suffer from uremic pruritis. Currently there are no approved products in the US for this condition. Patients are generally managed with a multitude of products including corticosteroids, anticonvulsants, antihistamines, and antidepressants -- with very limited success. So we believe that the anti-itch properties we have already established for CR845 could provide an important new therapeutic approach for this significant unmet clinical need.

In December 2014 we reported positive top-line safety and PK data from Part A of our proof-of-concept trial in dialysis patients showing that CR845 was safe and well tolerated across a 5-fold dose range after one-week post-dialysis TIW -- that is three times in a week -- dosing. At that time we also reported that, although uremic pruritis was not an inclusion criteria for randomization in Part A of that trial, three subjects entered the trial with worst itching baseline scores in the moderate to severe range; that is, greater than 4 on a 10-point VAS scale.

All three subjects received TIW dosing of IV CR845 and ended the one-week dosing period with reported worst itching scores of 1 or less. We view this data as encouraging early data suggestive of CR845 efficacy in this population.

The ongoing Phase 2 trial will enroll a total of 60 dialysis patients at multiple sites across the US and will measure the efficacy of CR845 compared to placebo in reducing the intensity of itch in dialysis patients over a two-week dosing period. Endpoints will include, of course, worst itching scores as well as a range of quality-of-life measures associated with pruritus burden, using a series of previously validated self-assessment scales. We expect to report top-line efficacy results in the second quarter of this year.

So it's evident that we have a transformative year ahead of us in 2015 here at Cara, with the start of our Phase 3 studies in acute pain, as we have outlined today; the readout of our Phase 2 proof-of-concept study in uremic pruritis; and the potential readout from our first Phase 2 trial in our oral CR845 program. We are going to be very excited to report on all that data as the year progresses.

Finally and importantly, we've accomplished all of this clinical progress and indeed validation on a very efficient capital basis. As Joe is about to discuss in a couple minutes, we ended the year with more than $50 million of cash on our balance sheet. And in the coming year we also expect to receive certain milestones related to our collaboration with Maruishi Pharmaceuticals in Japan as they progress CR845 for both uremic pruritis and acute post-op pain indications in their territory.

With that I'd like to turn the call over to Joe Schoell, our Chief Financial Officer, to go through briefly the financial results. Joe?

Thanks, Derek. I will be going over our fourth-quarter financials here on the call; and our cumulative full-year numbers can be found in the press release just issued today, as well as our 10-K, which will be filed later today. All per-share numbers I will be discussing are on a basic and diluted basis.

We reported a net loss of $4.2 million or $0.18 per share for the fourth quarter of 2014, compared to a loss of $2.1 million or $0.49 per share for the same period last year. The weighted average number of shares used in the per-share calculation increased to 22.8 million from 4.3 million shares for the respective periods, due to common shares sold in our IPO and automatic conversion of convertible preferred shares into common shares in connection with the IPO during the first quarter of 2014.

Collaborative revenue was $0.4 million for the fourth quarter of 2014 compared to $1 million in the same period of 2013. Clinical compound revenue was $515,000 and $14,000 for the fourth quarters of 2014 and 2013, respectively.

Research and development expenses were $3.5 million in the fourth quarter of 2014 compared to $2 million in the same period last year. The higher R&D expenses in the fourth quarter of 2014 were principally due to an increase in direct preclinical studies and clinical trial costs, and an increase in consultant services to support the preclinical studies and clinical trials.

General and administrative expenses were $1.8 million in the fourth quarter of 2014 compared to $1.1 million in the same period last year. The increase in the fourth quarter of 2014 was primarily due to increases in payroll and related costs mostly due to increases in headcount, directors and officers insurance cost, public investor relations cost, and stock option expense.

At December 31, 2014, cash and cash equivalents totaled $52.7 million compared to $12.4 million at the end of December 2013. The increase in cash and cash equivalents is principally related to the $57.8 million, net of underwriting discounts, commissions, and offering expenses paid in 2014, raised in our initial public offering, which closed on February 5, 2014. This increase was reduced by $17.6 million of cash and cash equivalents used in operating activities during the year ended December 31, 2014.

Now we will turn it back over to the operator for questions.

(Operator Instructions) Annabel Samimy, Stifel.

I want to ask you about the Phase 3 program. I just wanted to understand the decision around -- for designing a third Phase 3 trial. I know that initially it was just a hard tissue and the soft tissue; now it looks like you are looking for something in more of a general abdominal surgery setting. So just if you could explain the rationale behind that.

Then also with the Phase 2 data on both the oral and the uremic pruritis coming out this year, is this going to put you on a path to Phase 3 for next year? Or are you going to have to conduct additional Phase 2 trials? Thanks.

Great, Annabel; thanks for your question -- or two questions you snuck in there.

I'll sneak in another one too, soon.

Yes, yes. No; you only get two. I'm going to let Joe talk directly to the strategy behind the three Phase 3 trials for the acute pain indication. And then I'll come back and address your questions on oral and UP.

Thank you, Annabel. The idea here comes from -- from 2 to 3, it's a shots-on-goal approach: more shots on goal with three trials, and specifically two trials in abdominal surgery or soft tissue versus one.

The other comes from the fact that doing two trials each of 400 patients, they are really an appropriately sized trial, the 400 in bunion and the 400 in hysterectomy. We've got experience in those models. We know based on those sample sizes that we are well powered for an appropriate effect size in those models.

Speed at recruitment is also helpful when we separate these trials. Particularly hysterectomy is just -- obviously women with hysterectomy versus abdominal with a mixed bag of surgeries under that abdominal umbrella. Also the adaptation gives us an opportunity to ask for Special Protocol Assessment, to have the Agency buy into what we are planning on doing with that trial.

As you know we need about 1,500 exposures total. This is a new chemical entity, and those are the bottom line metrics for what the Agency is looking for.

So in doing three trials versus two, we have the ability to generate more exposures in men; not that we have to, but that's a nice-to-have. It also gives us, as I said, an opportunity to prove efficacy and safety in a broader patient population, which I think will make the Agency comfortable.

And again -- so that's the basic general idea. Now, you had a second follow-up question to that.

Yes, thanks Joe. Let me just address that. Annabel, for the other two programs you asked, with respect to the oral we really envisage the Phase 2 in 2015 being our first Phase 2 in that area. And we are looking at this point to run a second, initiating probably early in 2016, which would cover a slightly different clinical situation than we anticipate for the first trial. So with both of those trials we may be in a position to think about where we'd go for registration at some point towards the end of 2016.

For uremic pruritis, it really depends on the data, as we said a number of times. We think we've designed this Phase 2 trial very robustly. It certainly contains the appropriate, obviously, itch scales, but also the quality-of-life scales that we presume the Agency -- and we've seen from other guidances -- are going to look for.

So if that data is as robust as we hope and anticipate, then our plan is to look for guidance from the Agency on where we'd need to go for registration after that particular trial. So that's going to depend on our guidance.

Okay. If I can just ask the follow-up regarding R&D expense expectations with the third trial and then just in general for 2015. Clearly there's going to be a ramp up.

Can you size it for us in our heads a little bit? And where you are with cash in terms of completing those programs, and the cash for that.

Yes, so let me just -- Joe can tell you exactly where we are with the cash runway in just a second. Let me just say, in moving from two trials -- which of course were two larger trials of 600 patients in bunion and lap-hyst -- to three trials, two of which are 400 and one 600, the increase in expenditure there is actually minimal, a few million dollars in increased expenditure.

And we think that is obviously money well spent, as Joe has described the advantages of moving from two to three. In terms of overall runway we are still in a very healthy situation, and Joe can summarize that.

Yes, I would certainly agree with Derek in terms of the split. And the additional cost is not very large relative to the three trials.

With the cash on hand and the operating program that we have, we have sufficient cash and cash equivalents to cover our expenditures for at least 15 months. And that is without giving effect to our potential milestones with our collaborative partners. So I think we are in pretty decent shape right now. That doesn't say that --

Great. Thank you.

Charles Duncan, Piper Jaffray.

Hi, guys. This is Roy in for Charles. Thanks for taking the question. What are you guys thinking for the dosage for the Phase 3? Do you have any ideas there?

We do, Roy. Very simply I can say we are going to anchor those around the bunionectomy dosages that we've shown to be efficacious in our Phase 2 trial. We're going to pick a dose that is higher than that and a dose lower than that, with the idea that we would like to identify a minimal effective dose also.

Okay, great. That's helpful, thanks. Then maybe you could give us a little more update on the Maruishi studies, where they are at, and timelines for data maybe. Thanks.

Sure. Maruishi is making terrific progress in Japan. They've already completed their Phase 1 trial in healthy volunteers with I.V. CR845. They are presently planning to initiate UP trials with I.V. CR845 probably later this year.

Okay. Perfect. Thank you.

Alan Carr, Needham & Company.

I wonder if you could talk a bit more about that third trial. There's a preoperative and postoperative element to that in terms of administering 845. I wonder if you could talk about benefits and risks around that.

Then also, with respect to Maruishi you mentioned that some milestone payments may be coming. Can you talk a bit more about what might trigger those and the scale of those? Thanks.

Thanks, Alan. Joe is going to take --

Benefits and risks?

Yes.

Alan, pre-op and post-op dosing is exactly how the phase 2 trial in hysterectomy was dosed, as you may know. In fact, we just presented that data last weekend, American Academy of Pain Medicine.

The dose of drug was given about an hour prior to the surgery, and hysterectomy took about three or four hours, and then the next dose of drug was given when patients randomized, when they had an appropriate pain score. So it gives the anesthesiologist and the patient the ability to get drug onboard more sooner rather than later, which is an appropriate way to dose these kinds of compounds.

It is actually recommended by actually the American Society of Anesthesiology, trying to stay ahead of the pain scores for patients perioperatively. So the same way that we dosed drug in the hysterectomy trial in Phase 2, that's the way we're going to propose to dose it in Phase 3; and the same will be for the lap-abdominal trial as well.

So it gives you the ability to get drug onboard soon and then to maintain that drug level, blood level, over time. The drug will be dosed then on intervals every six hours.

So it gives your best chance for efficacy. So that's the benefit.

The risks -- if indeed this was a true centrally acting mu-opioid, the risk you would have, particularly when you pre-op dose somebody, is that you are worried about respiratory depression. And of course you would have to dose it with nasal cannula oxygen onboard, or some other type of supplemental oxygen.

The good news for us is that we don't have to do that. Because this drug doesn't penetrate the CNS for all intents and purposes, it doesn't cause respiratory depression. So that risk isn't there.

So in fact, I don't see any risks and only benefits by dosing it this way. And as I said we have done it before in Phase 2 in hysterectomy with some pretty nice results.

Great; thanks, Joe. Alan, to the second part of your question, or your second question regarding Maruishi, as you know the way that license is structured we receive milestone payments as they develop 845 in their territory; and we also receive milestone payments as we advance 845 here in the US. The next milestone we anticipate as they move into UP patients, or dialysis patients, as I said, later on this year would be a $2 million milestone payment to us.

Okay. Thanks very much.

Jim Molloy, Summer Street.

I was wondering if you could talk, Joe, perhaps a little bit more on the adaptive nature of the third lap trial and what should we be looking for there.

Then on the three trials, I imagine the third lap trial is the gating factor. But do you guys see as potentially the gating factor for getting these trials done? Which one should go fastest or slowest?

I'll take your last part first. We think that bunionectomy will likely start first and finish first, just because that trial -- those types of surgeries tend to enroll quicker. Very likely the lap-abdominal procedure study will be probably the longest to enroll, simple because there is maybe more patients in the trial; depends on the final number that we land with, with the FDA. As we stated, between 500 and 600 total patients, that's about -- you can do the math -- 125 to 150 per arm.

When it comes to adaptive design, the features allow the trials to be more efficient by guiding changes in study duration or sample size following review of the interim data. Now sometimes the study design or duration may or may not be needed following this review; but the adaptive design does allow us -- once we agree with the FDA -- to make modifications, if the interim data tells us that we need to, based upon robustness of the analgesic signal.

In the case of this trial, we haven't tested the drug in lap-abdominal or general abdominal surgery. However, we believe that these patients are going to react very similarly to the lap-hysterectomy trial that was done previously.

But for some reason, as I said, if the interim analyses are not what we would expect then that would give us a chance to, say, sample up and go higher in sample size to protect us against efficacy failure.

Okay, great. Then just maybe a follow-up a little bit on Annabel's question. The fourth-quarter R&D down pretty sharply. I know getting a guy like Joe onboard doesn't come cheap. I imagine that number is going in another direction.

Should we see something along the lines of third quarter for R&D going forward, or growing from there?

Yes, clearly as we initiate the trials, Jim, you're going to see that number increase.

All right. Thanks for taking my question, guys.

Ken Trbovich, MLV & Co.

I just wanted to follow up on the Maruishi side. I know, Derek, you mentioned the amount. Is that milestone payable upon initiation, or completion?

Yes, that is payable upon initiation.

Right.

Okay. The fact that we decide a large order that was just shipped, does that give us any indication that they are prepping that study for the early part of this year?

My goodness, you are a good detective, aren't you? Yes, I think we've guided that Maruishi plans to move into dialysis patients this year.

Yes. When you describe this as a Phase 2, help us understand it in the context or relative to the UP study that you have. Do you suspect that they're going to be looking at a larger sample size, more of what we think of as a 2b? Or is this more likely a 2a type design?

Ken, I couldn't answer that question specifically because I have yet to see their design on that. But it's going to be a Phase 2 trial, looking for (multiple speakers)

Okay. Then just sticking on the UP side, can you give us a sense -- we've heard anecdotally from others doing work in the space that enrollment in that study, or at least in that model, is fairly rapid. Are you having similar experience?

I think we are having an experience that we expected in terms of how quickly we can populate that trial. But as we've always guided, we expected to see data in the first half of this year and that is still our expectation on that.

Okay. Then for Joe, just on the lap-abdominal study, the third Phase 3 that you described, can you give us a sense for the male side? Are we talking about lap-hernia? What are we talking about, specifically?

No, it will be more maybe lap-prostatectomy, lap resection of the bladder, kidney resection, maybe gall bladder resection, that type of thing. In fact, hernia probably no; in fact, I would say almost definitely no.

Okay. Is the reason for that just the absence of pain with that model?

What, in hernia?

Yes.

Partially, yes. Also we are really looking to get into the abdomen.

As you know the hernia can be in the abdomen. It tends to be more in the groin than anywhere else, although you do have to open up the abdomen sometimes. That involves sometimes and sometimes not more use of mesh, which we are not really getting into or want to get into here.

What we are really looking for is that manipulation of organs for the visceral pain portion of the surgery. So again I think you're onto something there. We have to get patients to a certain level of pain that is meaningful enough so they can randomize.

Sure. Then just sticking with that idea of the measure of whether it's pain or the primary endpoint that you're looking at, can you give us an idea on the UP side what the relative measure is for itch that you are using for the actual study that is underway?

You are right, Ken; it's still a subjective measure, so it's a visual analog scale. And there we are interested in worst itching scores in the subjects at a two-week time point versus their baseline entry scores. That will be the primary endpoint.

But was there any limitation on enrollment in terms of they had to be at a 40 on a 100 scale, or a 60? Is there any sense for that on a screening criteria?

Yes, there is. We actually have a run-in period where their worst itching scores have to be on average above a certain level. I believe it's 4 out of 10 on a VAS scale over, I believe, it's a one-week run-in period for that trial.

Okay. Thanks again. Appreciate it.

Thanks, Ken. You get the prize for most questions.

Chiara Russo, Janney.

I think I've been questioned-out here. Just some quick housekeeping questions. You said on the Phase 3s, you said that they were going to stagger in their start; did I hear that right? One is going to start second quarter, probably that bunionectomy; and the other two were going to be later in the second half?

That's correct. If I ran the world and all things were perfect they would all start at the exact same time. But the reality is that the one that is going to start first and fastest will be bunionectomy. But the plan is to get lap-abdominal and lap-hysterectomy as soon as possible after those.

Okay, got you.

The good news is that we aren't competing for sites, right? Because they are all different sites, different types of surgery.

Okay, all right. Then for the oral Phase 2, that's also going to be starting second half of this year as well?

Possibly the first half of this year. In terms of completing that first Phase 2 trial, we think we're going to see data by the end of this year on that.

Okay, all right. Like I said, I think most of my questions had previously been asked and answered. So thank you guys for the time.

Charles Duncan, Piper Jaffray.

Just a quick follow-up. On the Phase 3 for hysterectomy, repeat dosing is going to be on an interval over every six hours; is that correct? Versus the Phase 2 where it was appropriate pain score. So is that a change from the Phase 2 to the Phase 3?

Actually, Roy, yes, you are correct. The dosing is going to be q 6 hours for the lap-hyst trial. I think you are mixing up your bunions and your hysterectomies there.

The hysterectomy Phase 2 was q 8 PRN; and that is also going to be q 6 in the Phase 3 trial.

I see. Okay, very good. Thank you.

Annabel Samimy, Stifel.

Just a quick question on the pre- and the post-hyst. I know that this was discussed at some point in the past, but can you remind us how you got comfortable with, like, quote-unquote, owning the side effect profile during the surgery [comp] to switch to the pre- and post- dosing?

Sure. Because in hysterectomy, the previous Phase 2 trial -- and you said it: you own all adverse events as soon as you dose drug, as soon as you randomize the patients. And our experience with a 200-person lap-hysterectomy trial already tells us that we are able to own any of those issues that happen intraoperatively, whether it is fluid shifts or the anesthetic gases that are used, intravenous opioids that are used.

And they can still come out of that procedure, get another dose of drug -- after they can randomize -- and still get another dose of drug and we can still demonstrate efficacy, which we have done, as well as safety. As well as I think the most important thing, the reduction in nausea and vomiting. So that's how I am very comfortable with it.

It also makes sense. That is how I used to operate, or that's how I used to deliver anesthesia when I was in the OR. So it makes total sense to do it that way; that's how it will likely be done in the real world. It's how these types of drugs, NSAIDs as an example, are dosed in the real world now.

And it's the best way for us to demonstrate efficacy. It's our best, as I said, shot at separation from placebo.

Okay, great. Thank you.

Thank you. At this time I don't see any other questions in queue. I would like to turn the call back over to management for any closing remarks.

Great. Thank you; and thank you, everybody, for calling in today. We look forward to updating you on all these clinical development programs in Q2. So thanks again. Take care.

Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Everyone have a great day.