Tvardi Therapeutics Inc (TVRD) 2017 Q1 法說會逐字稿

Good afternoon and welcome to the Cara Therapeutics First Quarter 2017 Financial Results Conference Call. (Operator Instructions) Please be advised that this call is being recorded at Cara's request.

I would 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 p.m. today and could 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 include statements concerning the expected timing for the announcement of the results of our ongoing and planned clinical trials, the expected timing of our planned clinical trials, 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 the markets that are potentially addressable by our product candidates and our expected cash reach. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in the company's 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, 2016, 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, whether as a result of new information, future events or otherwise, except as 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 on the call. Today, 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 candidate, 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 the projected financial resources required to advance our clinical plans for both I.V. and oral CR845 through multiple data readouts.

Additionally, we recently reported positive respiratory data from a Phase I safety study observing that I.V. CR845 did not significantly differ from placebo across 3 quantitative measures of respiratory safety and healthy individuals. We believe this further differentiates CR845's safety profile from traditional new opioids, which are, of course, linked directly to respiratory depression.

Finally, enrollment is not complete in our Phase II2b trial of oral CR845 for chronic pain, and we continue to enroll our adaptive Phase III trial of I.V. CR845 in patients with acute postoperative pain, and we expect to have 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 will take you through the progress in our other clinical programs. So as we've discussed previously and as a reminder, CKD-associated pruritus is an intractable systemic itch condition affecting approximately 60% of dialysis patients with end-stage kidney disease. The disease has a profound effect on quality of life, is highly correlated with increased morbidity and mortality in this patient population. And most importantly, standard antihistamines and corticosteroids are not effective in these patients, and there are currently no approved therapies for this indication in the U.S.

The positive data we reported in March was from Part A of our Phase II/III study of I.V. CR845 in this patient population. Part A, to remind you, was a randomized, double-blind, placebo-controlled study to examine the efficacy of 3 doses of I.V. CR845 administered after each dialysis session over an 8-week treatment period in 174 hemodialysis patients experiencing moderate to severe pruritus. We were very pleased to see that I.V. CR845 improved the primary endpoint of worst itch intensity by approximately 68% over placebo and also improved secondary quality-of-life measurements based on the Skindex-10 assessment tool by approximately 100% over placebo. We also saw statistically significant improvements in additional quality-of-life endpoints, including the 5-D itch endpoint, the MOS-Sleep scale and Patient Global Impression of Change and Severity at 8 weeks in I.V. CR845-treated patients. More information and details regarding these results are available on the Investors section of our website, which contains both the webcast conference call replay and presentation slides from the data announcement on March 28. And we will be presenting the full dataset from this trial at our upcoming CKD-associated pruritus KOL breakfast on May 16, and we will also be webcasting that event.

Looking ahead, we're planning to meet with the FDA for an end of Phase II meeting to determine an optimal dose to advance into Part B of this trial and define our broader path to registration in this indication. We will also be initiating an open-label 52-week safety study in hemodialysis patients in the second quarter of this year in this program. Also within the UP program, we expect to report data from a pharmacokinetic safety study of oral CR845 in hemodialysis patients later this quarter. The goal of this study is to define the bioequivalent tablet strength to enable the development of an oral formulation of 845 suitable for use in moderate to severe uremic pruritus.

Finally, we believe that by virtue of this mechanism of action, CR845 may be efficacious in other pruritus indications. And in this regard, we aim to submit an IND for 845 in chronic liver disease associated pruritus in the third quarter of this year and initiate a proof-of-concept Phase II trial in 2017.

All in all, we feel we've made significant progress recently at Cara in both the clinical and the operational fronts, and we certainly believe we have an exciting year ahead of us here in terms of clinical output.

So let me now turn the call over to Joe to provide an overview of our other clinical programs.

Thank you, Derek. As highlighted, we are 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 III trial of I.V. CR845 in acute postoperative pain and our Phase IIb trial of oral CR845 in chronic osteoarthritis pain.

So starting with our oral CR845 Phase IIb trial. I'm very pleased to announce that this trial is now fully enrolled at 480 patients and on track for a data readout later in Q2. As a reminder, this is a double-blind, placebo-controlled, multiple-dose Phase IIb design testing 3 tablets strengths of CR845 dosed twice daily over an 8-week period treatment in patients with moderate to severe pain. The trial design incorporates a 4-week titration period for a response followed by a 4-week maintenance period. The primary endpoint will be difference from baseline and pain scores in CR845-treated patients versus placebo at the end of the 8-week treatment period. Secondary endpoints include the change from baseline in the Western Ontario and McMaster Osteoarthritis Index, amount of rescue medication use and the Patient Global Assessment, or PGA, of osteoarthritis.

Now moving on to our adaptive pivotal clinical 3001 trial of I.V. CR845 in postoperative pain. This is a 3-arm trial testing 1 and 0.5 micrograms per kilogram of CR845 versus placebo in up to 450 patients undergoing various abdominal surgeries. The trial design accommodates an interim assessment for conditional power across doses at approximately 65% enrollment with an adaptation to optimum dose in subsequent progression to complete enrollment. 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 enrollment threshold for our interim assessment and expect to complete this analysis next month.

Finally, as Derek mentioned briefly, in April, we report results from a Phase I trial assessing the effects of I.V. CR845 on respiratory safety after bolus infusion in 15 healthy volunteers. As a reminder, respiratory depression is the most life-threatening side effect of conventional opioids, which act primarily at the mu opioid receptor subtype. This was a randomized, double-blind, 3-way crossover of 2 doses of CR845, namely 1 and 5 micrograms per kilogram, which is the proposed therapeutic and 5x or 5 times the therapeutic doses compared to placebo. Respiratory safety was evaluated by continuous quantitative measurement of end-tidal CO2, respiratory rate and pulse oximetry. We were very pleased to report that no significant alteration of any quantitative measure or respiratory drive was observed over the entire 4-hour observation period in patients administered CR845 as compared to placebo, even at the higher CR845 dose. The potential ability to administer I.V CR845 without an observable direct effect on respiratory function would be a significant advantage in the acute post surgical care setting, where patients are already at heightened risk of respiratory depression. Moreover, CR845's profile also aligns with the most recent standard of care guidelines for postoperative pain, which call for minimizing opioid-related side effects. An abstract covering the complete dataset from this trial has been selected for an oral presentation as part of the Journal of Anesthesiology Symposium on Sunday, October 22, 2017, at the American Society of Anesthesiology, the ASA, Annual Meeting in Boston.

To summarize, we have a busy clinical program underway in both pain and pruritus indications with multiple significant data readouts in the coming months.

And with that, I'll turn it over to Josef Schoell for the financials.

Thanks, Joe. As a reminder, the full financial results for the first quarter can also be found in our 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 sublicense by Maruishi of our intellectual property related to CR845 for use in patients with uremic pruritus in Japan. Of 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 costs and an increase in payroll and related costs 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 equivalents and marketable securities primarily resulted from the cash used in operations of $21.6 million.

In April of 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 equivalents 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 the line of Charles Duncan of Piper Jaffray.

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 that and if you could provide any color on timing there.

Yes. So we are, Charles, as we said before, and we will be requesting that soon. And our plan is to have an end of Phase II meeting with the FDA and finalize the dose we're going to take forward into our Phase III registration trial for uremic pruritus.

Okay. And any sense as to when you would be requesting that? Is that roughly midyear or by the end of...

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

Soon as we can. It just all depends on their schedule, but it would be reasonable to expect it to be Q3.

But there's no gating events from your perspective at this point?

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

Okay. And then regarding the Phase III 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, that trial is going to be expanded, just to reduce potential effect of noise in the data.

Sure. So it's a good question. I mean, there's really a couple of outcomes that can happen with this trial. And, of course, that's going to -- that data will drive the press release. But we can either continue both doses to full enrollment. We could drop a dose and continue enrollment, or if possible, we could stop for early efficacy. And really, any of those 3 are possible. We are still blinded, so we just have to wait and see what it looks like now. We have an 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 by 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 prespecified that we can go up to 150 per arm, but the IDMC will tell us how high we could go. If indeed we needed to go a little higher, maybe sometimes we do that. It really all just depends. I wish I could have a crystal ball and tell you exactly what it looks like, but until it's unblinded that's when we'll know. And of course, we have to make -- any of those changes, we'll make it in ClinicalTrials.gov as well and we'll have to tell our investigators. But for right now, we can go up to 450 total.

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

Correct. It all depends on the conditional power.

Our next question comes from the line of Annabel Samimy of Stifel.

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 setting for UP. And then how translatable is that for potentially bringing oral CR845 to the pre-dialysis setting, which would obviously be an excellent expansion opportunity? Because presumably, the pre-dialysis patients are not as renally compromised, so was there anything else that might affect the PK between the 2 populations?

Sure. So the 2 populations are absolutely different, and they're 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 in someone who, say, who takes a drug orally as an outpatient not on hemodialysis. And the data will tell us what the best way forward 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. They have obesity, hypertension. They're on many, many other drugs -- not that, that necessarily affects our drug's PK. As you know, we're a synthetic drug, and we're not metabolized, but we are renally excreted. And so one of the things that -- or many of the things that we're looking for is just an overall safety profile, tolerability profile between the 2 groups, whether or not indeed there is a difference in how an outpatient taking it orally not on dialysis would handle it 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 want to make sure we get a handle on with this study.

And just to extend that a little bit, 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 exposures from our I.V experience, we can model as being efficacious, so we can absolutely define which tablet strengths are appropriate for each stage there in terms of CKD patient.

Okay, great. And then on the OA side of oral CR845. So if pain relief can be established form the I.V trial in the postsurgical pain program, what do you expect the requirements will be from a development perspective for the oral drug for OA? So obviously, long-term safety is required. But how many Phase III studies would you need? What would a development program look for in OA?

Sure. So in OA, it's relatively straightforward. I mean, if this trial is positive for us, we'll go. We'll have a meeting with the FDA and then the Phase II meeting. It's very, very likely that they would ask for 2 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?

Yes, and we've outlined this publicly. So we would be able to complete our I.V program in postop pain, our I.V CR845 program in uremic pruritus in hemodialysis patients and finish the current oral program that Joe just outlined in terms of the oral Phase IIb study in osteoarthritis patients. Also within the context of the raise, we're going to look -- and we've said this in our guidance, we're going to move beyond CKD-associated pruritus and look at proof of concept and other conditions where we see pruritus as an intractable unmet need. And the first of these is likely to be liver-associated pruritus. And there, we'd aim to initiate a Phase II proof-of-concept trial a little later in 2017 in that particular condition.

Our next question comes from the line of Alan Carr with Needham & Company.

Can you, I guess, give us a big-picture view or strategy around the other pruritus indications? What -- you mentioned chronic liver disease, something you'll 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, Alan, and I think we've said that probably, we think, by virtue of the mechanism here, which is, if you like, at the end of the pruritic pathway actually on the C-fiber and blocking the release of pruritogenic substances from immune cells directly in the dermis, that this should be applicable across disease states. So obviously, we want to move into CKD non-HD since we think that pathophysiology responds well to kappa agonist. Beyond that, liver, as you know, we've seen proof of concept from the Japanese drug, REMITCH, which has had a label extension in Japan, an 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's some early evidence with perhaps nonselective kappas, that atopic dermatitis and some other dermatological conditions look interesting. And that's 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 3 main populations: CKD, chronic liver disease associated pruritus and dermatological conditions. And as you know and as we've said publicly, that's a very large patient population, large opportunity across there.

All right. And then you mentioned, Joe, that you had reached the 65% enrollment in the postsurgical pain trial for the interim assessment. Are you continuing to enroll now, or do you pause until after you had a chance to look at the data? How does that work?

That's a good question. What -- we're continuing to enroll, and so there's no pause. We continue to enroll 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 enrolling, and we'll take a look at the data as soon as we can, 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 -- how the spend will play out this year or maybe you can characterize the pattern? You mentioned that it's going to go into 2019, but you will have presumably more trials starting up. I know that you wrapped some up now, but how do we reconcile all them?

Well, I think the startup of the trials will be later on in the year. Probably Q1 and Q2 are 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 is going to be that -- the uremic pruritus...

Open-label, 52-week...

Yes. So that was not going to be that expensive?

It's not very expensive.

Our next question comes from the line of Arlinda Lee of Canaccord.

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

Right. So the analysis is based on actually an unblinding 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 horsepower a lot, right, 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 II/III adaptive design trial for that reason. So based upon what they see, they tell us and make recommendations as to whether or not it appears that what our original plan was, 125 per arm, seems to be appropriate. And if it is, we'll continue to enroll, targeting that rate. If it doesn't seem that we have enough horsepower based on the 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 arm as an example, right. So there's all kinds of options that we build into this by design so that we can just be smart or try to be smart about the next step after we've taken a look.

Okay. And the 65% -- is it 65% of the 120 -- the original 125 or the maximum 150? And is there a chance that you might be able to expand it further, if necessary?

Yes. There -- we can extend it up to 150 per arm. If we have to go beyond that, that's probably going to require a discussion with the FDA, but it just -- it all depends upon how many more we might need. I would hope that we don't need much more than that. But if we do and if it's not that much more -- and again that's a -- the FDA is involved in this process as well, right. This is a 3-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 indications. Are you -- how much of these additional indications depends on what we might do with the oral? Can you move forward with the I.V. to begin with and then switch over to the oral if it's maybe more amenable to whatever the setting is?

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

Our next question comes from the line of Ken Trbovich of Janney.

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 was the possibility that you'd stop the trial altogether due to efficacy. Should we assume that, that would only be looking at the primary measure in terms of pain reduction? Or are you guys interested in also seeing secondary measures like reduction in opioid usage coming out of this study?

Actually, I am 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 was set up is pain has to work first. The secondary endpoint that's prespecified is postoperative nausea and vomiting. That's the scale that we use. We also look at safety, and we will look at opioid-sparing effects as well. But all those 2 pieces are really building to 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 cash sufficient to finish the Phase IIIs. Does that mean that you folks think you're in position to file on both U.P. and I.V. form for both U.P. and pain in 2019?

Well, we're certainly in a position to complete both those programs, Ken. We haven't absolutely guided on the timing of filing the NDA. But it's obviously, as soon as we finish those Phase IIIs, we'd look to file the NDAs as quickly as we could.

Sure, sure. So depending on how late in the year, that sort of thing?

Yes, exactly.

Okay. And then just with regard to U.P. and obviously the fact that you've got an oral PK study in U.P. patients -- I'm sorry, I guess dialysis patients specifically, I guess one of the questions that it raises is whether or not part of your planning for the Phase III would include the possibility of only moving forward with one formulation, either oral or I.V.

No. So plan for the moment here, now, 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 was 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 study. As we think about case of enrollment 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 prepare to look at this data and looking at the possibility of multiple Phase IIIs? Did the enrollment go easy or more difficult? Sort of how would you characterize that process?

That's a good question. I think this enrollment went well and better than expected. These trials are always difficult to enroll, in general, pain trials. Clearly, OA enrolled faster generally than I.V. I think 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. A twice-a-day oral treatment chronically is something chronic pain patients are kind of used to, and so it made me pretty excited actually the way it went down, and now it's just about wrapping it up and getting the data out as fast as we can.

And, Derek, just from a pure development standpoint, are you guys sort of leaning more towards trying to complete those later studies completely on your own? Or would you consider entertaining the prospect of a partner following the Phase II results?

No. That's a great question, Ken. As you know, we've always had the view we wanted to retain U.S. rights on all our main programs. But if there's an opportunity for an ex-U.S. partnership under the appropriate conditions, of course, then that's something we're certainly going to look at.

Our next question comes from the line of Chiara Russo of Cantor.

Yes. 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. 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 bundle payment system with the I.V. formulation?

Yes. Chiara, thanks. As we've discussed before, I think on this call a couple of times, our view at the minute is 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 out with the bundle if you improve quality of care for those patients. And the precedent there recently that we've cited before probably is the Amgen Parsabiv I.V. molecule, which was recently granted pricing at -- with the bundle by CMS. And really, it's a drug that's somewhat analogous to ours. It's dosed 3 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 calcimimetic. And clearly, we have the same argument or perhaps a stronger argument in that there are no alternatives, as you've seen from our recent Phase II/III data, where we allowed so-called antipruritic co-medications in our patients, in our trial which were clearly ineffective. So there are no alternatives for CR845. It does allow, obviously, a higher degree of patient compliance, and more importantly, an effective therapeutic for that particular condition. So we think we have a strong case. Now that there's 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 antipruritics outside of the bundle currently? Or would you be the first?

No. There is no antipruritics that are effective. So if you look at the functional category within that legislation, the antipruritics named there are predominately antihistamines and corticosteroids. So these are clearly not effective. So no, 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's something that is going to be label specific? Obviously, you can kind of augment the drug profile with it. Just sort of your thoughts on that.

Yes. No. Thank you, Chiara. We were really excited about it, too. It kind of validated what we've always believed about this pharmacology. This is a kappa drug. It's not any opioid drug. And so even if it got into the CNS, it wouldn't cause respiratory depression anyway. This just proves the point. And what's also pretty exciting, we were invited as an oral presentation. And there are over 1,000 abstracts submitted to the ASA. We were 1 of only 8 that were actually invited to do this oral presentation, and they actually invited us to actually submit it for manuscript already. So that doesn't happen too often, at least not in my experience with the Anesthesiology 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 -- that -- the strength again on the 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 are even wearing oxygen. And so it's safe there. And we gave it at 5x the dose, right. So -- and 1x the 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 will also help 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 the human 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 2 weeks on the UP. Any sort of preview? Are you going to talk about uremic pruritus perhaps in the stage 4, 5 kidney disease patients? Kind of what should we expect going into that?

So Joe can answer this in more detail, Chiara. But really, the aim there is to provide some, if you like, end users. So these are some of the best-known nephrologists in the U.S. 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 effective therapeutics in the current standard of care. And a lot of people do question these nephrologists on how effective and the advantageous approach we have here with this particular molecule. So it's really a clinically focused event to allow end users to comment on CR845 and effectiveness there.

I mean, these are nephrologists who are in the trenches, treating patients every day. And they're seeing these problems every day, and that's why we want to put them in front of you so you can hear it from them, what they're dealing with -- and from not just the patients 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 and their itching and their pruritus.

Our next question comes from the line of François Brisebois of Laidlaw.

Yes. Most questions were answered. But quickly, I was just wondering is it fair to say that the receptor occupancy levels that were seen in the I.V. CR845 for UP should be a good readthrough for the postop pain coming up?

Absolutely. Yes. And pharmacologically, you're correct. So the concentrations in blood are exactly the same. Obviously, we have I.V. administration, so it's fully available. And we'd expect similar levels of receptor occupancy in both patient populations.

Okay, great. And then quickly, just one last one here. The quantitative Phase I respiratory data that just came out. Why did you guys look at the -- I think you mentioned it in the prepared remarks, but the 5-microgram kilogram. And was that planned out before the clinical hold happened in the first quarter or...

No, no. It actually was planned out after, and that's 5x what we believe to be an analgesic dose. So just to put some color on that, right, let's say an analgesic dose of IV morphine is maybe, say, 10 milligrams I.V., right, IV 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, 5x that dose. And that's a dose that would probably get you bypassing nausea and vomiting and getting you into things like maybe respiratory depression or apnea, right. So we're trying to choose doses that are meaningful. Obviously, the meaningful dose is the dose, 1 microgram per kilogram, and then some ex beyond that. We could have -- 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 was no incidents of any respiratory safety problem. So you just have to pick a dose. It's nothing that the FDA requires, but it's something that we wanted to have. I'm pretty proud of it actually because -- and it's got the attention of the American Society of Anesthesiologists, and I think that's evidenced by the fact of that early request for manuscript and to be put on their oral panel.

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

Great. Thank you. Thank you, everybody, for participating today, and we look forward to updating you 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 may all disconnect. Everyone, have a great day.