Good afternoon, and welcome to the Cara Therapeutics KORSUVA Injection FDA Approval conference call. All participants are in 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 will now turn the call over to the Cara team. Please proceed. Good afternoon. This is Will Gramig with Stern Investor Relations, and welcome to Cara Therapeutics' KORSUVA Injection FDA Approval conference call. The news release became available just before 4:00 P.M. today and can be found on our website at www.caratherapeutics.com. You may also listen to a live webcast and replay of today's call on the investor 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 potential timeline for launch of KORSUVA Injection, the potential timeline for reimbursement, and the potential of KORSUVA Injection to be a therapeutic option for CKD-aP, and dialysis-dependent patients. 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's filings with the Securities and Exchange Commission, including the Risk Factors section of Cara's annual report on Form 10-K for the year ended December 31st, 2020, and its other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward-looking statements made on today's call speak only as of the date on which they were made. Except to the extent required by law, Cara undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Participating on today's call are Dr. Imran Alibhai, Cara's President and CEO; Dr. Joana Goncalves, Cara's Chief Medical Officer; and Eric Vandal, Senior Vice President of Commercial. I'll now turn the call over to Dr. Alibhai. Thanks, Will, and good afternoon, everybody, and thanks for joining us. Today, we are very excited to announce that as of this afternoon, we received formal notification from the U.S. FDA that our lead product, KORSUVA Injection, has been approved for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis in the United States. This approval serves as a real watershed moment for patients undergoing hemodialysis, as KORSUVA Injection is now the first and only treatment approved by the FDA for chronic kidney disease-associated pruritus. Pruritus in these patients is an intractable systemic itch that occurs with high frequency. It has been consistently correlated with decreased quality of life, increased propensity for other comorbidities, including psychiatric disorders, and mainly related to increased risk of infections and systemic inflammation. Pruritus has been identified as an independent predictor of increased mortality in hemodialysis patients. With currently employed antipruritic treatments, such as antihistamines, unable to provide consistent, adequate relief, the approval of KORSUVA Injection today brings these patients one step closer to receiving the effective treatment which has been severely lacking to this point. Before we get to the details of the prescribing information, let me summarize the main highlights of the approval and the label on slide 5. Overall, we're very happy that the final label is consistent with our expectations based on our large phase III data set encompassing over 1,300 hemodialysis patients. Importantly, our preclinical and our clinical data has consistently indicated a lack of abuse potential and absence of physical dependency with KORSUVA administration, and we're very pleased that the control substance staff at the FDA has acknowledged this, and KORSUVA will not be a federally scheduled substance. Also importantly, KORSUVA is not metabolized through the liver. No liver enzyme interactions have been identified. The molecule is excreted whole predominantly through the kidney. Consequently, section 7 is absent from our PI with no drug-drug interactions identified. This is, of course, an ideal characteristic for use in the heavily medication-burdened hemodialysis patient. In addition, based on the observed safety profile of KORSUVA through our phase III program, no post-marketing studies are indicated at this time. Overall, we're extremely pleased with today's approval. We're now focused, as you're going to hear a little later, on working with our commercial partner, Vifor Pharma, to bring KORSUVA to patients as soon as we possibly can. Finally, I just want to point out that KORSUVA has been developed from first principle at Cara Therapeutics from compound screening and optimization through the whole of preclinical and clinical development. I'd like to recognize all of the Cara teams, present and past, who have worked so diligently through many years to bring this first-in-class compound to patients. Today's approval would not have been possible without their effort. With that, I'll now turn it over to Jo and Eric to detail the U.S. prescribing information and provide more color on the commercialization plans and the timelines for commercialization. Jo, over to you. Thank you, Eric. As Eric previously stated, KORSUVA is indicated for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. The recommended dose, 0.5 microgram per kilogram, is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each hemodialysis treatment. The dosage form and strengths are as follows: 65 microgram per 1.3 mils of difelikefalin. The FDA approval is based on 2 pivotal phase III trials, KALM-1 and KALM-2, as well as additional safety trials and supporting clinical trials. KALM-1 was a U.S.-only based trial, KALM-2 was a global trial. As a reminder, these trials are multicenter, randomized, double-blind, placebo-controlled trials to evaluate the safety and efficacy of KORSUVA Injection for the treatment of moderate to severe pruritus associated with chronic kidney disease in subjects undergoing hemodialysis. Subjects were randomized to either KORSUVA at a dose of 0.5 microgram per kilogram or placebo, administered as an intravenous bolus injection at the end of their hemodialysis 3 times per week for 12 weeks. In both KALM-1 and KALM-2, there was a significantly greater proportion of subjects on KORSUVA who reported a clinically meaningful itch improvement compared to subjects on placebo. That is 40% of subjects in KALM-1 and 37% of subjects in KALM-2 achieved at least a 4-point improvement from baseline in the worst itch NRS score at week 12, compared to 21% and 26% of subjects on placebo, respectively. In addition, subjects on KORSUVA experienced rapid and sustained itch relief, as you can see in the 2 graphs, which are included in the prescribing information. Moving on to the safety highlights of the KORSUVA prescribing information, KORSUVA is approved without any contraindications. Warnings and precautions include dizziness, somnolence, mental status changes, and gait disturbances. Centrally acting depressant medications, sedating antihistamines, and opioid analgesics should be used with caution during treatment with KORSUVA. Patients are advised not to drive or operate dangerous machinery until the effect of KORSUVA on a patient's ability to drive or operate machinery is known. The most common adverse reactions in greater than 2% of KORSUVA-treated subjects and greater than or equal to 1% higher than placebo include diarrhea, dizziness, nausea, gait disturbances including falls, hyperkalemia, headache, somnolence, and mental status change. As you can see on this slide, this is the adverse reactions table that is included in the label with the most common adverse reactions and their respective incidents. I'll now turn the call over to Eric Mandel, our Senior VP of Commercial, to discuss KORSUVA's injection, commercial planning, and readiness. Over to you, Eric. Thanks, Jo, and good afternoon, everybody, and thanks a lot for joining us today. I would like to start by providing a quick overview of the market for KORSUVA Injection for chronic kidney disease-associated pruritus in hemodialysis patients. Currently in the U.S., there are more than 500,000 patients on hemodialysis. 60% of these patients have some level of pruritus, and roughly 40% of the total hemodialysis patient population, or approximately 200,000 patients, have moderate to severe pruritus, and this will be our target patient population based on our indication and our label. If you go to the next slide. With the FDA approval of KORSUVA Injection, this significant patient population will now finally have access to an approved treatment option for their moderate to severe pruritus. To gain this approval, Cara conducted the largest worldwide clinical development program in hemodialysis patients with chronic kidney disease-associated pruritus. Because there are no approved therapies to treat moderate to severe pruritus for this patient population, KORSUVA will help fill a significant unmet medical need. As such, the FDA awarded KORSUVA with breakthrough therapy designation and priority review. As a reminder, the 2 criteria for breakthrough therapy and priority review are, one, the product must treat a serious medical condition, and two, the clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on clinically significant endpoints. Let's shift our attention to the projected U.S. launch timeline. Earlier this year, with our partner, Vifor, we initiated disease state education to help educate healthcare providers on the prevalence and pathophysiology of chronic kidney disease-associated pruritus in hemodialysis patients. Following our approval today, we expect to file both our TDAPA and HCPCS applications in the 3rd quarter of 2021 and plan to commence disease state education via the Vifor sales team also starting in the 4th quarter of 2021. In the 1st quarter of 2022, we plan to begin our full promotional launch of KORSUVA through the Vifor sales team. We also anticipate to have both our TDAPA and HCPCS applications approved and providing reimbursement to dialysis organizations and patients during the 1st half of 2022. As a reminder, Cara executed a strategic license agreement with Vifor Pharma in the 4th quarter of 2020 for the expanded commercialization of KORSUVA Injection in all U.S. dialysis clinics. The decision to partner with Vifor for the launch of KORSUVA Injection was made based on Vifor's established nephrology sales force and strong relationships with U.S. dialysis organizations. Vifor has an established nephrology commercial organization in the U.S., with more than 50% of its corporate net sales generated in the U.S. Vifor has over 100 sales representatives in the U.S. market and provides extensive access and strong relationships with the large dialysis organizations, the mid-size dialysis organizations, and the independent dialysis organizations, as well as nephrologists and other key stakeholders in the dialysis space. Additionally, Vifor brings an established market access team, as well as an existing supply chain infrastructure. Because of their well-established infrastructure and expertise in nephrology, as well as the dialysis space, and their partnership with Fresenius, Vifor has developed a strong portfolio of nephrology products, which includes Veltassa, Mircera, Velphoro, and Retacrit. As such, we believe Vifor is an excellent commercial partner to help us maximize KORSUVA Injection's market potential. With that, I will now turn the call back over to the operator for question and answer. Our first question comes from Jessica Fye of J.P. Morgan. Good afternoon. This is Daniel for Jessica Fye. Thanks for taking our questions. A couple for us. First, what's the typical timeline for reimbursement negotiation with CMS? Is there an opportunity for CMS to provide feedback on reimbursement and for subsequent launch to occur in early 2022? Second, in your view, do you see the warning language on the label regarding dizziness, somnolence, and mental status changes affecting prescription patterns? Thank you. Great. Thank you, Daniel. Eric, why don't you address the CMS timeline for review, and then maybe, Jo, you could talk a little bit about the warnings on the label. Sure. I'll start with the timing of TDAPA. Well, as I stated earlier in my section, we will be filing both our applications for TDAPA and our HCPCS codes in the coming weeks before the end of the third quarter. Depending on timelines of reviewing both application, we anticipate getting reimbursement in the first half of 2022. We currently plan a promotional launch for KORSUVA Injection in the first quarter of 2022. Jo, do you want to talk about the warning on the label? Sure. Yeah. The adverse drug reactions included in the precautions and warning section is important information for prescribers so that they can manage the patients appropriately when prescribing KORSUVA. We don't think that this will be a limitation for using KORSUVA, as KORSUVA is the only drug indicated for pruritus. Drugs that they've used in the past, that were used off-label, have actually greater dizziness and somnolence than KORSUVA has, if you look at the incidence numbers. We don't think this will be a limitation. An example of that, Jo, would be something like gabapentin, right? Right. Exactly. Gabapentin and pregabalin, if you look at the prescribing information, pregabalin, the dizziness is up to about 3% incidence. We don't think this will be a limitation for the drug. Great. Thank you. Thank you. Our next question comes from Chris Harrison of Jefferies. Your line is open. Great. Congratulations on the approval, Imran. I know this has been a lot of work and a lot of time, so really congratulations to you and the rest of the team. Thank you, Chris. Absolutely. I guess for me, and maybe it's just going back to the reimbursement, how are we thinking about pricing at this point? Is this a negotiation that you have to have with CMS? Is there some sort of guidance you can provide to us ahead of that time? As the corollary to that, is the price going to be set, at least during the TDAPA period, at commercial launch, or will we know that ahead of time? Then if I may, just a very short follow-up is there any CMC work or drug supply issues that are holding up launch, or is it simply just the logistics and the paperwork stuff? Thank you. Great. Thanks, Chris. I can answer the second question. No, there's no issues whatsoever with drug supply. The timing on the launch is all related to applications for TDAPA and clarity on our reimbursement code, as Eric Mandel was talking to. I'll let Eric Mandel talk a little bit about where we are on our pricing review. Eric Mandel. Yeah, sure. Sort of a multi-part question related to price. First part of the price is it's not negotiation with CMS. That's not how it works. We would set our WAC price, then we would get reimbursed initially at our WAC price, but then eventually under TDAPA, we would get reimbursed at the average selling price, plus zero, not our average selling price plus 6%. We haven't finalized a price yet. We have completed all of our pricing research and work to date. We're in discussion with Vifor, our commercial partners, to determine our final pricing and contracting strategy for KORSUVA Injection. We anticipate to have that final decision in the coming weeks here. I'm trying to remember what the other part of your question was. Would we know the timing? No, that was basically it. Yes. Okay. Yeah, the timing, and you basically just said that, so that's cool. Okay. Okay. All right. Well, thank you very much. I'll hop back in the queue. I appreciate it. Thank you, Chris. Thank you. Our next question comes from David Amsellem of Piper Sandler. Your line is open. Thanks. I have a couple of questions on the commercial landscape. Is it your expectation that you're going to see patients step through gabapentin or pregabalin or antihistamines before getting KORSUVA? Do you expect that because this is an on-label use and it's sort of, not sort of, but it is first of its kind in terms of the indication, that you think you're going to be able to garner a lot of share in terms of just frontline usage in these moderate to severe pruritic? What's the best way to think about that, at least early in the commercial launch? Thanks. Yeah. Thanks, David. Eric, do you want to relay our thoughts on that? Yeah, sure. Actually, we did quite a bit of market research in this area to understand how doctors see it utilized. I think conservative therapies will still be utilized as first line. Keep in mind, many of these patients have been itching for years and have tried many of these first-line agents. For example, it'd be emollients and creams and things like that because they have dry skin, and it's important to actually keep the skin moisturized. They may try antihistamine. They may or may not stay on them. Where we see the product fitting is right after those conservative therapies, many of which don't actually control these patients' itching, and prior to using a product like gabapentin or pregabalin. That's what was fed back to us by nephrologists when we talked through the profile with them. That's where we see it fit. Many of these patients have already tried and failed many of these options, so they might actually be able to initiate therapy right away on the drug because most of these patients have had itching for quite some time. Just to remind you, David Amsellem. Yeah. David, just on the, if you like, current standard of care, about approximately 40% of the patients we had in our phase III program were concomitantly taking antihistamines and still qualifying with moderate to severe pruritus for randomization. Yeah. The science has known for some time that this is a histamine-independent mechanism for chronic pruritus. Now, thankfully, the therapeutics have caught up with the science here, and this is really the first therapeutic that directly addresses the pruritic pathways. Great. Yeah. If I may sneak in a follow-up, just what's the therapeutic dose for gabapentin as an antipruritic, and then what's the incidence of somnolence of that therapeutic dose as an antipruritic? That's one for Jo. Jo, do you know what dosing is? Yeah. The dosing is uptitrated to UC effect, to what the patient can tolerate. Of course, in this patient population, it's the dizziness that becomes an issue. In their label, I can't recall exactly the number. I believe it's in the 20s. pregabalin is a little bit more clearer because it's a newer drug, and so it's 30%. I believe it's, yeah, it's 20%. It's around 20%. somnolence and dizziness is 20% in gabapentin. It is an uptitrated dose. I'm not quite sure at exactly what point that was experienced, at what dose. Yeah. Sorry, David. I can't provide you with more information. It's not really that clear when those effects were seen. Yeah, that's helpful. I was just trying to get at what the somnolence rate are for the gabapentinoids. That answered the question. Thanks. Thanks, David. Thank you. Our next question comes from Jason Gerberry of Bank of America. Your line is open. Hi, good afternoon, good evening. This is Xiang for Jason. Thanks for taking my questions. I guess first one is just follow up on the dizziness and drowsiness. There's language around warning against driving right after the medication, and there's some language around that you need to make sure the patient is okay to drive and operate machinery before people then go on to do their tasks. I'm just curious, how do you practically see the reality of this driving warning playing out and whether you see that as being a drag or not on the utilization? Maybe if you can speak to how often these patients drive themselves home after dialysis, that would be helpful as well. Sure. Thanks, Chi. Jo, do you want to take that one? Okay. Right. That will ultimately be a discussion between the nephrologist and the patient, the treating nephrologist and the patient, and weighing up and when looking at the adverse drug reactions, when we look at the data, patients experienced dizziness. It was 6.8% versus 3.8% in placebo, and 4.2 and 2.4% for the somnolence. It really is the minority of patients who experience these adverse reactions. It again, it will be based on the discussion and not all patients, as we said, 90+% of patients won't experience it. If they don't, then they should be fine to drive. That will be up to the prescribing physician to make that decision with the patient. Got it. I'm just curious, based on the clinical trial experience, how are these patients monitored for their ability to drive home and whatnot? Are they sort of like have a waiting area, sit there and wait for 30 minutes to make sure that they're okay? I'm just curious, what kind of. Right. What kind of procedures you see dialysis centers, take? Right. potentially implement to mitigate that potential risk of drowsiness that may lead to patients inability to drive. In fact, as you can see here, there is an adverse reaction, but as you may know, hemodialysis patients post-dialysis are incredibly fatigued. They themselves already have some fluid shift repercussions such as feeling dizziness, et cetera. Many of these patients don't drive home on their own anyway. There are precautions already taken for these patients, not specific to drugs, but just the process of hemodialysis. That would bode well with taking the drug. Got it. Maybe just another one from me. You talked about some of these patients are already on antihistamines, so I'm just curious, there's also safety language around advice against caution, against using sedating antihistamines along with IV KORSUVA. How do you see that sort of play out? Do you think physicians would still combine the use of antihistamine with IV KORSUVA, or do you think that they may have to pick and choose one or the other? Maybe, Eric, you can speak to this as well, but to date. Sure. They haven't had other options. Antihistamines were the predominant antipruritic agent used. Obviously with the approval of KORSUVA for the indication specifically for this patient population, that could change. Eric, maybe you can speak more to that. Good question. A couple of things. One, I think Jo hit the nail on the head with specifically saying that they don't have a lot of options. They give them sedating antihistamine. Typically, doctors or nephrologists admit they don't work very well, and a lot of times they give them to patients to help them sleep at night because it doesn't help with the itch. I would envision that many doctors would probably remove their antihistamine if it's not really helping their itch and utilize our product. I imagine some doctors will probably add our product on top of that. Keep in mind, Jo, correct me if I'm wrong, I believe our clinical trials, we did add our drug on top of it. It's not like we haven't seen that being done and actually have patients have good results with it. There's a caution in our label to monitor the patient if they are on both. I think many of our nephrologists would probably opt for KORSUVA. This is helpful. Thank you. Maybe just one last follow-up from me. I think, management had talked about maybe cite analogs and that had a pricing in the $10K-$12K range, a sort of like analog for how sales I could potentially think about the pricing of IV KORSUVA. I'm curious, do you have any update thoughts on the pricing of IV KORSUVA based on the label language that you have seen today? Yeah, no, just as Eric indicated earlier, Chi, that we've done our pricing research with our commercial partner that's under review, and we'll be announcing a price point in due course, prior to the launch. Got it. Thanks so much. Thanks, Chi. Thank you. Our next question comes from Annabel Samimy of B. Riley FBR. Hi. Thanks for taking my question, and congratulations from me as well. Just a couple here. As far as education plans are concerned, can you talk about how you're going to roll that out at Medical Conference directly and who's specifically responsible for it? Are you going to have any role in that whatsoever? Thanks. Yep. I'll leave that to Eric, but that's the commercial. Education is actually going to be directed by Vifor from here on in, Annabel. Eric, do you want to add some color to that? No, I think that's it. I think our next big meeting is ASN in the fall, and that would be our sort of launch meeting from the medical side. The Vifor team would be on point for that. Obviously, the Cara team will be supporting them both on the medical and the commercial side in whatever we can to help them be successful in launching the drug. Got it. Okay. Just going back to reimbursement, I know since CMS put the ruling out for all drugs approved post-2020, it seems that TDAPA is a relatively straightforward process. Are there any examples of that not working? Is there any risk that you don't get TDAPA for one reason or another? No. You're absolutely right on TDAPA. The rule reads that all new drugs after January 1st, 2020, will qualify to TDAPA. The key is the definition of new drugs, CMS defines it by NDA type. KORSUVA is an NDA Type 1, which means it's a new molecular entity, NDA Type 1s will qualify for TDAPA. We envision that we will get that. Every approval in the space will have to be dependent on what their NDA type is and whether they will get it or not. We're the first company to will be going through TDAPA in this new revised version. Parsabiv went through, that was under a different set of rules for TDAPA. There's no example of someone not getting it, we do anticipate to get that. Okay. One last question that's kind of related. After they make an adjustment post 2 or 3 years, I think it was 2 years, 3 years, I can't remember now, but after that TDAPA period, I know that there was an issue with Parsabiv getting the appropriate pricing, probably because there are other options available to them. Do you have any worry about not being able to get an adjustment to the bundle post that TDAPA period? Yeah. A couple things. A little bit different than Parsabiv. Parsabiv went into the bundle with Sensipar and generic Sensipar. What went into the bundle was a blended rate across all three products, not just a rate for Parsabiv. We would be very different once we go into the bundle. It would be just our branded product. That's sort of the major difference between what happened with Parsabiv and what we see happening once we go into the bundle. Okay, perfect. That's very helpful. Thank you. Thanks, Annabel. Thank you. Our next question comes from Charles Duncan at Cantor Fitzgerald. Your line is open. Yeah, thank you. Thanks for taking the question. Imran, let me add my congratulations to you and the team for this approval. Long time coming, but well done. Quick question regarding pricing, but it really isn't about pricing, it's more about pharmacoeconomic analysis. I guess I'm wondering if you could remind us as to what are some of the key considerations that you have in thinking through the pricing of the drug. What is the main clinical value for patients? Go ahead, Eric. Yeah. That's a complicated question. Pricing is a complicated issue. Obviously, the clinical benefit is actually we're providing itch relief for these patients that have never had it, and it's a significant impact on the patient's quality of life. That's hard to define and actually measure and put an easy economic value on it. There are other areas potentially down the road to look at in pharmacoeconomic and HEOR studies. It's hard to do in your clinical development program because the numbers are pretty small, and to see differences in a small short-term study usually are hard. Certainly, there are areas we will look to during the TDAPA period to collect pharmacoeconomic data which justifies utilization of the product. I'm trying to think. Does that answer your question, Charles, or? Yeah. Yeah. Okay. Understood that it's complex, but I think you addressed it, and we'll look forward to that additional pricing information. The other thing is, just last thing on that is, we've done actually quite a bit of pricing research, both with payer organizations and dialysis organizations and working through what scenarios look like to best optimize the pricing point. Okay. A follow-up question regarding Vifor and the terms. I know you probably haven't disclosed specifics, but could you remind us whether or not there are any revenue milestones or changes in terms of the royalty rate with regard to the sales of the product over time? Yeah. In the U.S., Charles, the next upcoming milestone is with the approval today. There's a $50 million equity investment from Vifor, and that will be at a premium to our stock price. In addition to that, you'll recall we had a 2018 license agreement with Vifor Fresenius related to co-promotion in Fresenius clinics in the U.S., and per that license agreement, there's an additional $15 million payment due upon approval. In totality, there's a $65 million related to approval of the product. In the U.S., there's a set of commercial milestones, $240 million in total, which we'll be eligible for, which are obviously tiered in relation to commercial sales. As you recall, overall, in the non-Fresenius clinics, it's actually a profit-share arrangement. Here in the U.S., 60% Cara, 40% Vifor, and within Fresenius Clinics, it's a 50/50 profit split. Thanks, Imran. Last question for you is, this is a big milestone for any company to get the first product approved. I guess I'm wondering, as you think about the implications for investment in the pipeline and new candidates, I guess any kind of change in your perspective on that or conviction? Yeah. Well, I think as you're aware, Charles, we have a very strong balance sheet presently. This approval and the prospect of revenue in the next 2 quarters is only going to strengthen that balance sheet. As we continue to develop the oral formulation for KORSUVA and really multiple clinical populations, we're going to have this income advantage that's going to be initiated here, which is going to fund that other part of the pipeline development. Yeah, very significant to get the approval and equally significant that we have these existing advantageous license agreements that are going to help us drive the other part of the business related to oral KORSUVA development, which of course broadens the application for KORSUVA beyond hemodialysis and then to other patient populations, as you're aware. Yeah, this is very, very important for the long-term strategy. It's a big deal. Congrats. Thanks for taking our questions. Thanks. Thank you. Our next question comes from Joseph Stringer of B. Riley Company. Your line is open. Hi, everyone. Congrats on the approval and thanks for taking our questions. Two commercial questions on the Vifor collaboration here. The first is on the profit share agreement and in this case, with Vifor's sort of established commercial organization in the U.S. here and the strong assets they have, what are your initial thoughts on sort of operating margins for the drug here in the U.S., at least an early sort of sense of that relative to perhaps some other margins with other similar drugs? Second question is on the penetration into Fresenius versus non-Fresenius clinics. What are your expectations on the relative contributions on U.S. sales for each of those market segments? Thank you. Thanks, Joey. Eric, do you want to take that in terms of operating projections and expenses for KORSUVA? Yeah. I guess, were you asking relative to other products and with Vifor? Is that your question? Could be relative to other Vifor products, but maybe just your initial thoughts for KORSUVA on operating margins. Yeah. For Vifor, we have a profit share. We expect to have a good gross profit. The other advantage that Vifor has is they have an existing sales infrastructure that is already paid for through their other product lines. Instead of having to add sales representatives in order to promote the product, they're adding it to the existing bag and infrastructure, which creates efficiency for them. I think there's a lot of value to them by adding this product to the bag because it doesn't have a significant increase in headcount in order to promote the product. A lot of that profitability, gross profit split with Cara will fall heavily directly to their bottom line. The second question you had asked about Fresenius versus other organizations? Yeah. Obviously, we're hopeful that our relationship with Vifor and their relationship with Fresenius will help us get off to a very quick start at the Fresenius organization. I think our Vifor partners have good relationships at DaVita and the mid-size. I would expect those to do well as well. We're hopeful that Fresenius will be more accelerated given their relationship. Great. Thanks for taking our question. Thanks, Joey. Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star then one on your touch-tone telephone. Our next question comes from Oren Livnat of H.C. Wainwright & Co. Your line is open. Hey, thanks for taking my questions and congrats to everybody there. I want to follow up on that last question about profitability. There's a huge range in revenue assumptions on the sell side for you guys for next year, and I assume the big variable is obviously the profitability. Can you just confirm, firstly, that whatever revenue you're recognizing, that is in fact the operating profit split, gross margin's obviously a part of that, but after whatever commercial spend they allocate to this product and gross cost, obviously, that's what you'll be seeing, your 50% share. I guess, you just mentioned that they don't need to add material headcount. Can you confirm, is this going to be promoted by all 100 or 100 plus reps in the U.S. in the first position? Do you think this is going to require a major promotional or marketing spend? Some of these numbers that the Street has suggest dramatic profitability in the first year of sales, and normally we don't see that in launches, first year, big operating profits. Can you just help us maybe all get on the same page? Yep. Eric, do you want to talk to the promotion aspect of that? Maybe, Oren, just quickly, yeah, the revenue we're going to recognize is going to be the revenue minus the marketing fee associated with Vifor's costs on distribution and marketing. There's no outlay from Cara, in essence, as we launch the drug, but there is a consideration for distribution and marketing fee related to Vifor's activities. Eric, do you want to talk about the promotion activity for Vifor? Yeah, sure. A couple components of that. You first mentioned around the profitability and efficiency. It's quite an efficient model because it's a highly consolidated market. Keep in mind, DaVita and Fresenius represent about 80% of the overall dialysis space. If you add the next 4 mid-size dialysis, you're up to about 90% of the market and 6 major customers. A lot of that can be driven top-down. That will create a level of efficiency from a promotional standpoint. Also, the nephrology specialty is a relatively small specialty compared to a lot of other pharma specialties, and it doesn't require primary care where you get into significant resources to get to it, including a large sales force. It's a relatively efficient model to get to, so I think you can see pretty quick uptakes. We've seen that with the last product to launch into this space, to see a fairly significant uptake. If you've got an existing infrastructure in place that you're leveraging and not adding to that, you can have pretty efficient profitability margins. I forgot what the second part of your question was related to the margin. Well, you mentioned revenue in the next couple quarters. That implies operating profits almost out of the gates and, theoretically, that's possible, but that's not something that we're typically used to seeing, right? Like operating profits. If you're allocating 100 reps in the first position, that was part of my question, some carrying cost of that sales force is automatically getting slapped onto this product, right? I guess I just want to understand how quickly we'll see revenue, basically, for you guys. Imran Alibhai, do you want to handle that? Yeah, go ahead, Eric. That's fine. Yep. Again, to answer your question on the sales force and allocating a part of its sales force, there's a difference between an allocation and an actual increase in expenses, right? You can allocate a portion of that. In our agreement with Vifor Fresenius, we have an agreed-upon percentage from the promotional amount that's subtracted from the overall gross profit, then we share that, if I'm correct in my assumption, Imran. Is that right? Yeah. We would expect to generate profit from that pretty early on. All right. Does that answer your question? Yep. Thank you. Okay. Correct. Thanks, Oren. Thank you. I'm showing no further questions at this time. I'll turn the call back over to Imran Alibhai for any closing remarks. Okay. Thank you everybody for participating in this afternoon's call. I'd also like to thank the entire Cara team, our study investigators, and all of the patients who have participated and continue to participate in our clinical trials, and we look forward to updating you again very, very soon. Thank you, everybody. Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may all disconnect. Have a great day.