Chris, thanks a lot for making it, and thank you everyone for tuning in on the webcast as well. Yeah, Sumant, thanks for having us this morning. If you want to give a few, brief opening comments, and then we'll... Yeah, I mean... Yeah, mean... Yeah, again, thank you so much for inviting us here this morning. I mean, Cara Therapeutics, we're at a really interesting time. We have a product approved, as Sumant said. It's being commercialized by CSL Vifor. We now have three consecutive quarters of really strong growth by CSL, so we're really pleased with the progress we're seeing in the US. We have a couple events happening, namely on the payer front with CMS, I'm sure we'll talk about. We're really excited about our development program. That's who we are at Cara. We have three late-stage programs, one in nephrology, and two in medical dermatology with our oral difelikefalin. We feel really strongly about. It really serves a huge unmet need in this marketplace across both those franchises. We have a strong development team that brought, you know, through IV KORSUVA and brought that to market, and this development team is working to bring oral difelikefalin to market in both, these two franchises over the next few years. Great, thanks for that. As you mentioned, we'll start with the product that's on the market being sold by, by your partner. You mentioned CMS, and that's become a, a relatively hot topic now, given we have this product that's already reimbursed, and then you're going to have a different era of reimbursement starting when this current period ends. There was a lot of discussion in your recent call about that, but how do you best characterize what's going on right now on the reimbursement front? Well, this is a one-payer market. I mean, these patients undergoing dialysis that receive KORSUVA are reimbursed through Medicare. Mm-hmm. You know, as you rightfully point out, right now, we're in this period called TDAPA, where we have two years of pass-through adjustment or pass-through reimbursement. That would expire next year. CMS every year puts out a new rule, and we've really worked hard with CMS to, you know, make innovation available for patients even after this period. They came out with a proposed rule, as you know, this past June, or this June, late June. Yep. In the proposed rule, we're actually quite pleased with, with certain aspects of it. Namely, 1, they're adding more money for a drug like KORSUVA past the, past the TDAPA period, so that's a positive. There's three significant concerns we have with the reimbursement methodology and, and again, we discussed on the call. These three elements, the first one being that the money does not follow the patient. Mm-hmm. It's spread across all dialysis treatments. Two, CMS now proposes a 35%, quote, unquote, "haircut" to the ASP that reduces the funding. Three, you know, it appears, reading the proposed rule, that the new money sunsets after three years. Those three elements are concerning to us, and what that would mean, it would reduce the funding. The process that we're in is in this comment period now, so we're in a 60-day comment period with CMS. That will expire August 25th. CMS will put out their final rule in November. What can we control at Cara? I mean, we're certainly going to comment on those three elements. Mm-hmm. Very poignantly comment that that still does not solve funding for patients that really deserve a product like this and, and future innovation, to be honest with you. The second thing at Cara we're going to do is request an extension of the TDAPA period for a full two years. Yeah. We think we have a really strong case. Our TDAPA period was under the umbrella of no new funding, and we certainly believe that's had an impact on some physicians in terms of their reluctance to use KORSUVA in a wide way. We're going to request CMS to provide an extension for another two years, so we can collect proper utilization cost data. Right. That's an interesting point you brought up. If physicians, some of them are reticent to prescribe this because of the reimbursement dynamics, I guess if you had 100 physicians, what percentage would you say would, would have that reticence? Yeah, it's hard to put a, an exact number on that. Mm-hmm. I mean, qualitatively, what we hear is that, you know, based on their experience with the only other drug to kind of go through this TDAPA period, Parsabiv, is that physicians, you know, felt that if there's no new funding after the two years. Yeah ... that, you know, if they put patients on therapy. Mm-hmm ... they would be asked to stop patients in two years. That's indeed what happened. Sure ... to Parsabiv from Amgen. You know, they were at the whim of the dialysis organizations and the policy- Mm-hmm ... and they couldn't override that. You know, their fear is, "If I put a lot of patients on, if there's no more funding or it's significantly reduced, I may be at the whim of these dialysis organizations that tell me I can't use it. Right. Parsabiv is a good analog because it was a TDAPA product, but it's not a perfect analog because you had Sensipar, which had gone generic, right? Right. In this case, you do not really have any generics. You, you have some things that were used off-label. Yours is really the only approved product for this indication. Do you have any prior instances of products which have been successful going against CMS's draft rules, and the final rule being extremely different? Well, you know, so to your latter part of the question, there is precedent for CMS to change their proposed- Mm-hmm ... rule to the final rule. Indeed, that's what the comment period is for. Sure. You, you address certain things that you want CMS to think about prior to the final rule, and there is precedent that that's happened. You did mention Parsabiv, and I think that's, you know, it's an appropriate analog, like you said, because it was the only drug to receive this pass-through reimbursement like we did. It, it's a very different market archetype. Mm-hmm. You know, when it went into the bundle, you're right, it had a generic equivalent. Yes, new money was added, but the financial incentive all shifted to the generic, and Parsabiv went down 75%. Mm-hmm ... you know, pretty immediately- Yeah ... upon it entering the bundle in 2021. For us, we do not have a therapeutic equivalent. I do kind of stress to you, though, that the limitations in the CMS proposal, though, puts physicians, providers in a real ethical dilemma in my mind, because if you put patients on, We have patients on therapy now, quite a few. Right. If there's insufficient funding, there's nowhere for them to go. They've already tried some of the older medicines that we know are ineffective, right? Yeah. The antihistamines, topical steroids to a degree. You know, that's why we believe we have such a strong case with CMS, and the external community is also commenting as well, 'cause bottom line is you've got to provide innovation. You've got to provide access to these therapies. Mm. Policy does drive prescribing behavior. Yeah. Fundamentally, if you don't believe that, then, yeah, a policy like CMS puts out is okay. Right. Fundamentally, policy does drive behavior. Yep, that's a good point. We have a bit of a chicken-and-egg situation here, right? Because there could be not as much prescribing simply because of these dynamics that you mentioned, but you need prescribing to get to actual utilization rate, so you can get the best possible reimbursement when steady state happens. If I were, like, let's say, a CSL Vifor salesperson, what would be my pitch to a doc right now, given all these things coming, coming in? Like, how is this product, if for people who actually sign on to use this product, what's the hook that, you know, makes them use it? Well, it's been since day one. There's a huge unmet need. I mean, roughly 40% of these 500,000 patients. Yeah ... that are undergoing dialysis suffer from moderate to severe pruritus. We know the treatments are ineffective for what they had before, if they got treated before. Right. You know, antihistamines were the standard of care, and we know they're ineffective. This is not a histamine-mediated, you know, condition, disease. The pitch, the sales, you know, the promotion has been very consistent. I mean, a huge unmet need, and we have a solution that's been approved by the FDA, the first and only drug approved by the FDA to treat this condition. Bottom line is, you know, we paint a picture of the patient, and if you've talked to patients that suffer from severe pruritus, I mean, the, the impact on quality of life is, is absolutely significant. You know, we had a capital markets day in February, if you remember, and a prominent doctor talked about a patient basically saying: "I need to stop dialysis. I'm fine to go on hospice because I can't take this- Right ... itch anymore. The pitch hasn't changed. It's all about efficacy and safety. It is reimbursed fully right now. Sure ... at ASP outside the bundle. Yeah. There's no restrictions on that, and there are certainly, for providers, a financial incentive at this point. You know, my narrative to you right now is that, yeah, I mean, we're concerned in the future if CMS puts this in its final form as is. Got it. I, I am concerned that for the industry as a whole, yes, KORSUVA, that access to innovation would be severely restricted. Right. If we come to a fork in the road right now, where TDAPA is ending, what are the types of scenarios? A couple of easy ones would be like, yes, you get exactly what you request from the CMS, and things change, and you get maybe a two-year TDAPA extension. You get good utilization rates, and then it, it just is all, all fine. What if there's an eventuality where you do not get what you want? How is the organization preparing for that? Yeah, I mean, you know, listen, I mean, we're, we're going to, in this comment period and even beyond, you know, with other stakeholders, politicians, other lobbying, I mean, you know, we believe we have a really strong case with CMS across those 3 elements in the methodology, but also an extension of our TDAPA period for a full 2 years, you know, so we could collect the proper utilization and cost data with the guys now that, you know, there is funding. You know, listen, worst-case scenario, I mean, they, they put the proposed rule in its final form. You know, certainly, you know, we know there's a huge need for this product. Would we have to be more aggressive on contracting with our partner, CSL Vifor? Yeah, probably. Mm. That probably is. I mean, the financial incentive needs to be there for dialysis providers to some degree. Right. If you look at, you know, therapeutics investing, you have this FDA, which is the agency that kind of is the gatekeeper of all things safe and efficacious, right? On, on, on this product specifically, you do have investors who understand, like, the, the therapeutics part very well. There are some who understand the, the services part very well as well, and now you have this whole new agency, CMS, which seems even more sort of unpredictable versus the FDA, which is- Mm which is somewhat of a different way of putting things. What's your mechanism, other than simply writing in comments to the CMS, by which maybe you can request a, a true audience with them, Zoom or whatever you like, but how, how do you do that? Is there a mechanism to do it? Yeah, this is. Well, let me just be clear. I mean, this isn't, like, something we just started with CMS. This has been a five-year process with CMS, led by Cara. Now we have a partner, CSL Vifor, that's fully, you know, on board with us as well, helping. This has been a year-over-year process of working with CMS. Yes, we've had meetings with them, clearly, and we have moved the needle, right? Yeah. Let's be clear, in the proposed rule, they did change their TDAPA policy. They are adding new money. Right. That's not budget neutral. It's incremental. It's a step in the right direction. In our comment letter, you're gonna hear me say, "I'm I applaud that." They recognize that they need to adjust the bundle to pay for innovation because it's required. We have moved the needle through all those efforts, and we'll continue to do that during the comment period. It's a bit more didactic during the 60-day- Sure ... comment period. We submit something electronically, as other stakeholders will, and we'll also try to engage outside of that comment period, you know, with CMS, if we can, other politicians. We'll, you know, we're gonna continue to keep up the fight. Yeah, it's selfish a little for Korsuva, but it's also for patients. I mean. You will see comment letters from patients, I'm sure, and it'll all be posted, you know, publicly. Then your partner is, is very entrenched in the dialysis space. It's among the best partners you could have, right? What, what are they saying about ordering patterns? Why I'm asking that is I'm trying to get a sense of how good of a sense Cara as an organization has to manufacture the right number of vials at the right time for your partner, and how, how do investors get a good sense of what inventories are, things like that? Well, we rely on our partner, but we have clear view, you know, at a clinic level, what the ordering is. Yeah. We see the same data CSL sees. Right. I mean, we're partners. You know, again, like I mentioned in the preamble, I mean, we're very encouraged with now three consecutive quarters. You know, you had the big buy-in from Fresenius in the third quarter, which was a good thing. It made some of our reporting a bit challenging, rightfully so, but that channel dynamic was meant to, you know, really activate all 2,600 of their clinics. We have clear view of, of the clinic ordering patterns, and I mentioned, I mean, you know, we had a 46% increase in quarter two versus quarter one in vials being delivered to the clinics. Yep. That, that's really a good marker for demand. It's a threefold increase since Q4. Right. You know, we had 20,000, we're up to 67,000 vials. We're seeing clear patterns across all the dialysis customers. You know, Fresenius, 50% of their clinics are now dosing patients. That's after really three quarters. Yeah. It's a good penetration. Yeah, I mean, you, you mentioned the inventory. I mean, there's a wholesaler, you know, buy-in from the Cardinal, McKesson, but that's to anticipate future demand. You know, the channel dynamic that's a bit unique in our market has been what our customer did, Fresenius, buying all that product centrally, which is unheard of. Right. That's how much they believe in the product, and they put it in all 2,600 clinics. We're seeing that burn down pretty rapidly now. Got it. Sometimes when I sit here in the US, I forget there's a world outside of here, right? You do have this product being sold by partners ex-US as well. What are some of the dynamics that we need to keep track of ex-US that might influence things like, usage of the product, maybe payer dynamics or something else? Yeah, like you said, I mean, the product is called Kapruvia in Europe. It's fully commercialized by CSL Vifor. Yeah ... as well in Europe. It really just started promotion in the fourth quarter of last year. We're now up to seven countries that have launched. Right. Yeah, we got approved in April of last year. It takes some time, country by country, you know, to get pricing and reimbursement. We're launched in seven countries, you know, the two big ones, Germany and France, and we're seeing really good patient and sales growth just two quarters in. What to look at is, you know, clearly you don't have this kind of quote, unquote, "cliff of TDAPA" like we do in the US. Right. We don't have the same systems in Europe. Pricing is a bit different, we're really encouraged about the patient and, and patient demand. Mm-hmm ... and sales growth. We're seeing what we expect, is that over the next, you know, couple months, 12 months or so, more and more countries are gonna slowly come online, and you're gonna see that continue to ramp up. It really, to us, speaks to the merits of this drug. I mean, the testimonials we're hearing from patients and providers, namely in Germany, are very consistent with what we hear here. Okay. They don't have the kind of barrier, potentially, of funding. Right. We're, we're encouraged. You know, for Cara, you know, we get 10% royalty off those net sales, so we, we would expect to see that continuing to ramp up over time. I'd also, you know, quickly mention outside of US, Japan. Sure. You know, we expect to get an approval in Japan, you know, really in the coming months. It's imminent. I mean, we feel really good about getting that approval. Great partner, Maruishi, who's commercialized with Kissei over there. They have, you know, a very large sales force. It's a very mature dialysis market. Mm-hmm. We're encouraged there, too. We get 10% royalty- Right in that as well, coupled with the $2 million milestone upon approval. Got it. Then coming back to the US before we move on to the pipeline here. Sure. What would investors or I guess, what would the company and then investors know before the rule goes final in November that could help us, you know, build up better margins, for example? Yeah, well, my friend Ryan here, my CFO, always says, "You'll know when we know." That's the truth. Yeah. We'll know publicly together. They'll post it publicly, the final rule. Okay. I, I don't think we're gonna get any wink, wink, nod, nods before, to be honest with you. Right. We'll know together. Like I said, we're really focused on commenting on those 3 elements of the reimbursement methodology, and we're also focused on requesting an extension for a full two years of TDAPA. Yep ... based on really sound rationale. Okay, got it. Now we'll move to the pipeline with oral KORSUVA. You have a lot of interesting programs going on there. Just step back and take a look at the mechanism of action of the product. You have it in, like, in trials for atopic dermatitis, itch and atopic dermatitis. You have it for the nephrology, as you mentioned, and you also have notalgia paresthetica. If you pick all of these, it looks like notalgia paresthetica has a clear line of sight from a neuropathic point of view on the itch, and your product works more from a neuro perspective versus some of the other, you know, pure derm products, for lack of a better term, right? How would you characterize your level of confidence in each of those indications based off of the mechanism of action of your product? Maybe that's a question for Jo. Yeah, it's great for Jo. Please. Good question, Sumant. Indeed, the drug we've has been demonstrated to have a strong neuromodulatory effect, that's why we've seen strong data in notalgia paresthetica, which is a neuropathic-driven itch. We also have data to demonstrate that it does have some inflammatory component as well, and that's why it has worked in CKD, and that's what we've demonstrated with IV KORSUVA. I do want to now hone in on atopic dermatitis, where that itch is a neuroinflammatory-driven itch. You need both of those components to address the itch. Currently, a lot of the drugs out there, specifically when we look at the topical space, the drugs are specifically anti-inflammatory agents. While they are very effective in addressing the, the lesions and somewhat of the itch, they don't always comprehensively address the itch because there's a strong neuro component as well. That's what we've demonstrated in our AD clinical study, the KARE Phase 2 study, that the drug was effective clinically. We saw that it was able to reduce itch in patients, especially with mild to moderate itch. Sorry, mild to moderate atopic dermatitis with strong itch. Also, and you will see that in the publications just recently published, that we have also strong objective data in our biomarker data as well. It's demonstrated that it's able to downregulate the pruritogens associated with atopic dermatitis, that's really important. Taking that all together, yes, strong neuromodulatory effect, seen strong in neuropathic itch, important in AD, which has got that combined neuroinflammatory-driven itch, but also effective in our CKD, and that's the beauty of the product, that it can work broadly across disease areas. Got it. You do have an internal readout coming for your atopic dermatitis program. What do you expect to learn from that, and how could that inform us on the outside, what that means for the program in atopic dermatitis? Yeah. We have an internal readout. I want to just remind the audience that this is the readout for Part A. This is a standalone study. I don't want people to get confused that it's an interim assessment. It is a database lock at the end of 12 weeks, and that information, what we'll glean from that, and what will inform us, We'll understand the dose to move forward into the Part B, as well as the second pivotal study and the sample size. That is, we're gonna assess the data, both the efficacy and the safety data, looking at the data that we receive from the top line, and we have internal thresholds that we'll be using to determine to move forward into Part B and KIND two. We feel really good about these internal thresholds, Sumant. We've vetted those with both key opinion leaders as well as we've done some market research with community dermatologists, and they've assessed our internal thresholds to be both commercially and clinically viable. We feel very confident and that we are in a good place, as soon as we receive the data to make those, to assess the data and to move forward. Got it. If you look at this from, you know, an investor point of view, the very fact that you have a go decision on that versus a no-go would mean that you have more confidence in the program going forward, simply because you have data that suggests quantitatively and qualitatively that product has a better chance of success. Absolutely. -on the second part. Okay. Absolutely. I mean, that's the, you know, the point of Part A, is to give us that information. We would move forward knowing that and feeling confident that the product is effective, that the safety profile is favorable to move forward in the atopic dermatitis space. Right. Moving to notalgia paresthetica, you've had some really interesting data on that, and the unmet need is pretty high in that indication. If you look at these three programs that you have for oral KORSUVA right now, what's the chance that enrollment or something else might proceed at a pace that is different from what you expect? What data could you receive first, and I know you've, you have some goalposts for when you might receive data on each of the Phase 3 programs, but what could make that change? Is there a pace of enrollment that could be different, or how are you thinking about that as a company? I think we feel very confident about the timelines we've put out there. That's based on our experience with the clinical studies from an operational perspective. Of course, you know, there could be an accelerated enrollment. You know, that's always a pleasant. Mm-hmm. you know, it's a pleasant, situation to face. For now, I think we are very comfortable with the timelines that we've put out there. Got it. When's your next kind of planned interfacing with the FDA on oral KORSUVA? What sort of data would you need, or would that be after you get your phase 3 results, or is there any kind of, for lack of a better term, an interim point in time where you can meet with the FDA to inform your program better? Yeah, I mean, we will be following the clinical development milestones when we interact with the FDA. Yeah, so just the traditional milestones. For sure. We don't foresee anything before that. Yep, got it. If you look again at these 3 programs, you already have a program, the product approved for at the IV part. Mm-hmm. -for dialysis. You have a program now in nephrology. Would that be the, the most kind of clear, like, "Here, here's a product that works just in intravenous format. We have an oral format now or going to have one, and here's the, the indication that would work," sort of most de-risked from a, from an outside point of view? Which, which one of the three would you say that would be? I always lead this. I don't have a favorite child. I mean, we, we have 3 late-stage programs. Mm-hmm. that we're really encouraged about. I mean, you know, I would say, you know, the regulatory pathway is validated. Right. You know, we know the division that approved the IV KORSUVA is the same division that will, you know, work with the NDA upon submission in all three of those indications. Yes. We have a regulatory pathway validated. We believe we have an MOA now validated in the setting that we have for IV KORSUVA. Yes, it's in nephrology, but we actually have, Jo alluded to, very strong Phase 2 data. Mm-hmm. -in atopic derm, as well as notalgia paresthetica that you alluded to, that was just published in the New England Journal. We feel very strongly that it's a fairly de-risked molecule at this point. Right. It's about clinical trial execution. Yeah. We have a team that's already demonstrated that it could do this from the clinical development through regulatory, through approval. Got it. I, I'm very confident in that. We have a minute left, I'm gonna involve Ryan here. The way we looked at this when we, when we picked up coverage of Cara was, you had this product, IV product, out on the market that's generating cash for you, and that cash could be used to do all the good stuff you could do on your development program on the oral side. From your position, how do you view the need for financing versus what could come in using oral KORSUVA, IV as... Oh, sorry, IV KORSUVA as a means to do that? Sure. You're correct. That was the original thesis, that the cash flows from IV KORSUVA would cover the pipeline. The most important thing, and the only thing we spend money on at Cara, is our pipeline. Mm-hmm. We don't spend any money on the commercial launch. We don't spend any money on Kapruvia or the Japan approval. My job is to protect that pipeline, make sure they're fully funded, and they are. Those three programs are fully funded, and on our call on Monday, I gave guidance that we have at least a year of cash. Yeah. I want to extend that runway, so that would mean pushing the runway into 2025. I'm working on opportunities to do that, potentially non-dilutive opportunities. We've discussed these cash assets we have at KORSUVA. We're in a very opportunistic position where we actually have assets that are generating cash, and that would be Kapruvia and the potential Japan launch. The hope is to be able to monetize that and extend our runway into 2025. All right, great. Thanks a lot. We're out of time. I think the next time we meet, we're probably gonna focus 90% on the oral KORSUVA part. There you go. That's the hope. Thank you. Thanks, everyone. Thanks for your time.