Newsfilter article unlocker

All right. Good afternoon, everyone. Thanks for being here. We're very excited to have Jennifer and James from Trevi here with us for this session of the Morgan Stanley Global Healthcare Conference. I'm just going to get through a quick disclosure. For important disclosures, please visit www.morganstandley.com forward slash research disclosers. With any questions, contact your institutional salesperson. I am Judah Frommer, one of the SMID biotech analysts here. And like I said, we're very excited to have Trevi with us for this session. So maybe we'll start off. It's been a year of significant progress for Trevi. Before we dive in, maybe give the audience an intro to the company and your chronic cough programs from a high level. Sure. First of all, thank you for having us. We appreciate it. And thank you for those of you that have hung around till the end of the day to hear us. So Trevi is a simple story. We're a single asset company focused in chronic cough indications. Three indications, idiopathic pulmonary fibrosis cough, other interstitial lung disease cough, and refractory chronic cough. There's been a lot of sort of movement on the competitive landscape around that. We have aligned with the FDA on our path forward and our lead indication of IPF cough. We've started those trials. We can get into more detail. So we are in phase three, looking for a lot of data to start reading out, some later this year and then second half of next year. So it's been an exciting time to be in it. I'm joined by Jim Casella, who's our chief development officer, so he's had a very busy summer sort of getting all this off the ground. Great, and before we jump into the essay, maybe let's start with unmet need in chronic cough, get us situated on the epidemiology, how patients are managed currently, and what the potential opportunity is here for TREP. Yeah, so chronic cough's been an area that Big Pharma's been interested for a while, very big market. So just to orient you, just to kind of take each of the slices, idiopathic pulmonary fibrosis has about 140,000 prevalence of about 140 thousand. Eighty-five percent of them have cough. So, you know, two-thirds of them has uncontrolled cough. You can think about 100,000 patients. It's one of the number one complaints of these patients. So we all know there's been a lot of work in IPF. Those are anti-fibrotic, slowing down disease. I think what our program brings to these patients is actually helping to manage their quality of life and day-to-day living. The other interstitial lung diseases, ITF is an interstital lung disease. It's about half that market. You essentially double that whole opportunity. So a lot of leverage in that market overall with probably an additional clinical trial. Refractory chronic cough is a very big opportunity. That's sort of two to three million patients. A little bit blows up the specialty model we're in. But the reality is there's been, I think, 20 drugs tried in RCC, all of which have failed. And we should probably talk a little bit about why we think we're different. But we are approaching that market. We're not going to change our specialty sort of focus there. We are going to go after the most refractory patients and maintain our pricing there. So each of these indications is quite large. And as I mentioned up front, we're alone left in these cost indications. So really exciting commercially. Final point on that is maybe you're going to get to this later, but this, you know, respiratory has been an area very manageable commercial-wise by biotech. So we're excited about the situation we're in. Okay, great. And we'll get into refractory chronic cough specifically, but maybe just starting with some history around Nalbufine. How's it differentiated from other cough mechanisms that have been explored? Yeah, and that's sort of the crux that, you Know, when we got into this space, there was probably 20 programs going on, and most of the programs were dealing with cough through peripheral mechanisms in the lung, which sort of makes intuitive sense. I'm one of the two co-founders of the company, and my co-founder's a neurologist, and he had been sort of kvetching at me for a while that neurological cough is not a lung problem, it's a brain problem. It's a response to, if you think about IPF, it is essentially fibrosis of the lungs, and your brain is sending this signal, acknowledging this fibrosis. And so Tom was convinced that whatever drug you treated this with, it had to be neurologically active. So what's interesting about our mechanism, we work peripherally in the lung, but we also work centrally inthe brain. So along that whole cough reflex arc. And I think as our data is rolled out, it's had a very big effect in almost everyone seems to come on early. So I think over time, these other mechanisms have failed. We're sort of left. AndI think what we all take away from that is managing cough centrally is important. Okay. And I guess within the context of opioids, how does abuse potential compare to other opioids? How well has that been characterized? And, you know, we'll get a question out of the way up front that typically we'd save till later, but potential for scheduling risk in your mind. Yeah. And, I'll touch on it. Jim, you add any color. I know you're going to get into a lot of trials, so you'll be chatting away for a while. So, now, bupene is an opioid, but as I like to explain to people, not all opioids are the same. There's four opioid receptors. When people hear the word opioid, they think of morphine, fentanyl. Those are all new agonists. There is a class of drugs that are called mixed agonist antagonists that were designed to get away from drug addiction. So our drug now, buphine, actually blocks that new receptor and works at kappa. So the experiment we were running is, is kappa helpful? And so that's kind of where we started off. The drug's been around as a sub-Q injection for decades, so it's been unscheduled. We had to do some work. We did some human abuse potential work.We've done some respiratory depression work. All of that's been clean. We believe this drug's going to stay unschedule. So we picked this drug intentionally because we thought we could get away from a lot of the baggage that has plagued opioids. Okay, great. And you mentioned that, you know, it's an older drug. So just on patents and NIP more generally. You've been proactive on patent strategy. Maybe talk a bit about the protection for Heduvia. Is there anything we should be looking out for on this front going forward as well? Yeah, so it's an old drug, so no composition of matter. We have method of use patent issued that's quite broad in our IPF cough program, basically covers chronic cough and IPF with nalbufine, so broad claims. We had spent a lot of time and energy in the company over the last sort of year, filing additional claims around the label, a lot of clinical work that's been done. We'll continue to expand that. Issued patent goes through 2039, so we'll have a good 10 years of protection. What we're now trying to do is build around the level and extend that out to 46, 47. So a lot room to move here. There hadn't been a lot work done in cough. There was a lot unknown. So we feel we've got a lot opportunity to patent. Okay, great. And maybe just transitioning to your lead indication, like you said, IPF-related chronic cough, at a high level, maybe help summarize the data we've seen thus far, safety and efficacy from the Phase 2 studies, and maybe loop in, you had a presence at ERS recently, so what were key takeaways there as well? Sure. So, we have good experience with our IPF population. We've run two studies to date that were enabling us to start the Phase 3 program. The first was a crossover study, the canal study, We learned a lot from that study. We did some dose ranging. The real important study that we ran was the CORAL study, which we reported out. This was a parallel arm study. We did somedose exploration in there. We were able to really determine our effect size. We were also able to figure out the best optimal dose to bring forward. So what that did for us is we picked a 54-milligram twice-daily dose. We brought that to the FDA, had a discussion with them about our dose ranging, about the efficacy that we saw there. So in our coral study, we did see about a 36 percent differential from the placebo control arm. We saw optimal dosing there. We had a 108 milligram twice daily dose that was also included in that trial, but the 54 milligram dose was really the sweet spot dose. So we saw really the optimal efficacy. We Saw no additional benefit from the 108, though, so it was easy to make the decision to bring that forward. And I think on the safety side, what we saw was a very well-behaved and well-characterized safety profile that we've seen throughout our cloth program, but also with the history of the drug that existed before we even got into the cloth space. So we see typically CNS and GI-type side effects. These are typically transient. These are triply, typically mild in severity. And I think that was the package that we brought to the FDA to get us to the end of phase two meeting and into the phase three program. Okay, great. So maybe just getting into the phrase three, you know, maybe let's talk a bit about design of these studies and you've initiated the first study. Any update on status of the second study as well? so the design really follows from the coral study that was a really important study on a number of different dimensions but it had a two-week titration period and a four-week fixed dose period so what we brought forward was that 54 milligram dose versus placebo now we're looking at a longer duration trial with the same primary endpoint which is 24-hour objective cloth monitoring We did exploration and confirmation of PRO data from the CORAL study. We brought that into the Phase III program. So the end of Phase II meeting was a really great meeting for us in that we got agreement with the FDA that we were looking at our primary endpoints, the same as what we saw in the CORAl study, and the secondary endpoints that we wanted to bring forward on the PRO side. they agreed that those were important endpoints to bring forward. The differentiation now is really where we see the duration of the trial, what the FDA is looking for in terms of long-term safety, and what they're looking for in terms Of showing durability of effect in terms of efficacy. So with that, we are running, as our Ocean 1 study, our long-duration study, 52 weeks of placebo-controlled safety data with our primary efficacy endpoint at 24 weeks of fixed dosing. So with a two-week titration and 24 weeks of fixed-dosing, so that's where we'll get our primary advocacy read with 52 weeks of long safety data. Our OCEAN2 trial, just to sort of fill in what we came out of the end of phase two meeting with, is really a confirmatory on the efficacy endpoint, where the FDA was not as strict in terms looking at the duration of the trial. We came to an agreement that a 12-week primary efficacy endpoint for the OCEAN2 trial would be sufficient for showing confirmation of the effect on cloth, and we're powering that trial for our primary efficacy endpoint as well as our key secondary endpoint. The OCEA1 trial, which is the longer duration trial, we have a number of key secondary endpoints, and we're powered. That's a 300-patient trial. We're powered for all the key secondary endpoints. With Ocean 2, the shorter-duration trial, we are powered for the key secondary and the primary endpoint. That is a 200-patient trial. So that comprises the bulk of the data we need for efficacy and long-term safety. And timing, Judah. You asked about Ocean 1 is running. Ocean 2 will start this quarter. Great. And then maybe just back to dosing in the phase three. Like you said, you tested the 108 in Phase 2? I guess maybe just a little more detail on the 54-meg dose selection. What did you see at 108 that convinced you that 54 is the right dose or, you know, was 54 just good enough? So what we saw was a modest increase in the effect on cough frequency through the cough monitor with the 108 dose. But as we looked at very important parameters on the patient-reported outcome side, the secondary endpoints, when we look at things like patient- reported cough severity, patient reported cough frequency, we saw no added benefit with the 108 dose. So, you know, just in terms of risk-benefit, we Saw the highest benefit, really, when you look at all the data together with the 54-milligram dose, with no added benefits from the 108. Right. Okay. Great. And then maybe just a little more color on the titration strategy for the Phase 3. You've characterized the AEs with the Dubio as being early, transient, and mostly mild. So what have you learned from prior studies that helped you to optimize the titration here? So we did a really careful analysis of the adverse events that occur both in our river program in the RCC space and also in the IPF space. And one of the things that is true across both patient populations is that we have the very similar type of adverse events, CNS and GI in nature. And what we see is in those two very different populations, we see the same type of adverse event profile. But importantly, what we see in the analysis of when do those adverse events come on, they come on early. They come on with the initial dosing in titration, the 27-milligram dose trend. And we also see a very similar duration of the adverse events, the CNS and GI, slightly varying between some of the specific adverse events of interest. So what we saw there was a characteristic sort of shorter duration, usually coming on with the onset of dosing. So what мы did for the Phase III program in IPF is we increased our titration period where we look at QD dosing with the 27-milligram dose. We did that before, and we started off with that in the CORAL study. But instead of a couple of days, we made it a week of QD nosing. The idea there being that maybe we can mitigate some of these adverse events of CNS and even some of the nausea and potentially vomiting, with nighttime QD dosing for one week, we mitigate those. And then we go into a 27-BID for another week. So that came out of our analysis of the onset of the adverse events and sort of the nature of the duration of these things. So we think that titration is going to be very useful in mitigating some ofthe effects that we saw even in coral, some ofthee effects thatwe saw in river, where we can maybe get rid of some of those effects while the patients are sleeping. Okay, great. And like you said, Ocean 1 evaluating the primary endpoint in 24 weeks and 12 weeks for Ocean 2. The Phase 2b coral, you evaluated at four weeks of fixed dosing there. So talk to us a little bit about confidence that cough reductions you observed at that four-week time point will translate to longer time points. Any data with nalbufin or the mechanism that, you know, kind of adds comfort on this? Yeah, so I think there's two ways to look at that. We have data from our previous trials when we were looking in paragon nodularis where we had run a study that was a year long. And in that, we saw full maintenance of effect, so no loss of the durability of the response. So we have data with itch. There's previous data that was captured in pain. So I think underlying these things that, you know, these are mechanisms or indications that have maybe a common underlying mechanism that leads to this concept of sensitization, we have not seen empirical data that suggested that we would see any kind of loss of durability of response or tachyphylaxis in that time period. Also, I think, you Know, there's a possibility that the mu antagonism that we have inherent with our pharmacology, different than the mu agonism that you see with the morphines and the fentanyls of the world, I think that switch from agonist to antagonist mechanistically can help prevent the tachyflaxis that can occur at the receptor level as well. But I think the empirical data with our itch studies tell us that there could be some confidence there. Of course, the data will be coming out of the Ocean One study, primarily, which is a longest study, but we don't expect to see any kind of tachyphylaxis. Okay. That's helpful. And then maybe just touching on some operational aspects of the study. First, on the objective cough monitor that you're using, you've leveraged it in prior studies. There's some regulatory history with that device. So maybe for those who aren't as familiar, give us a little bit on how the device works and how it was validated. So we can thank Merck for a lot of the heavy lifting on the validation of that. I mean, they learned the hard way that they needed to do a little bit more validation work with the Gefa-Pixson studies. They did all that work. I think Vitali Graf, the company, benefited, and I think as an industry, we benefited from all the analysis and from the hard work that was put in there. So that set the stage for us where, you know, some things were learned during the whole Merck program. Now, in our case, we did work out an agreement with the FDA that once we did the Coral study, as others have to do there's a validation study that goes on after the fact actually we reported out the results of our validation study when we had our investor day and what we showed there was that when you look at the compression algorithm that is used specifically for this system where they they have human raters and they they actually score it's a chest sensor which picks up acoustic signal, and there's also an audio monitor. They're scored. The raters can hear the co-op, and they count them in a compressed algorithm. So we had to validate the algorithm from the uncompressed to the compressed. I think that was one of the initial issues. We showed that there was extremely high reliability going from the uncompress to the compress. And also the inter-rater reliability. These are people that are highly trained to listen for cough sounds and count them. And we did inter-rater reliability with three different raters, and we had very, very high relationship, high correlations between each of the three raters. So in the world of validation, we feel very comfortable that this was adequate and sufficient to satisfy the needs that we have in the IPF program. It further enhanced the validation that was done previously by other companies. So we feel very comfortable as a very different kind of experience now with VitaliGraph's system versus the early days when there were some issues around that. Okay, some good background. And then maybe just talk about site selection for the Phase 3 program a bit. How many of these sites do you have experience with, and how many have participated in other Phase 3 programs? So I think we had a great experience with our coral study. We have a lot of those sites that are still involved. And the beauty of what we're doing here in the U.S. is that we're working with a lot of the specialty centers that are part of the Pulmonary Fibrosis Foundation network. There's 80 to 90 sites there. We have tapped into a vast majority of those websites between Ocean 1 and Ocean 2. That's where the bulk of ILD patients, IPF and non-IPF patients go for their care. So we really are tapping into centers that have the patients, well-characterized patients, and a lot of those centers have cough experience. Okay, great. And maybe we should have done this earlier on, but maybe we characterize kind of standard of care for IPF cough. You know, there are some off-label treatments. There are no approved therapies. And with that in mind, how do we think about clinically meaningful outcome on the primary endpoint in phase three? And while we're there, maybe help us with assumptions around power. Yeah, that's a good question. We can tag team this a bit if you want, Jim. So standard of care, they try all the things you try when you have a long viral cold, you know, Teflon pearls, codeine cough syrup. They'll try some gabapentin. None of it really works. It's been a frustrating aspect of the disease. There's been publications put out that 30% reduction in cough is clinically meaningful. We've also had patient boards where we've consistently heard any level of cough reduction is helpful to me. I think the real answer here from our trial perspective is we did a lot of work about what's important to patients and their patient-reported outcomes. And frequency is definitely important, but cough severity is equally important to them. So how severe they cough. And so that's our key secondary endpoint. I think hitting our primary and reducing cough and then reducing cough severity is clearly clinically meaningful. As far as powering and, you know, happy just at a high level, we've assumed a 30% effect size on reduction in objective cough. In our Phase 2B trial, we saw a 36% reduction, so I think we've been appropriately conservative here. So we feel good about that. Okay, great. and what would be supportive of a win or positive data with respect to the secondary endpoints? How important are those from a regulatory and commercial perspective? Obviously, it sounds like the PRO aspects are important. Yeah, I'll come on commercial. You can come on regulatory. So Jim mentioned our bigger Ocean One studies powered down through seven endpoints. We really only probably need the primary and key secondary for regulatory approval. But in those other secondaries, I mentioned to you that the antifibrotics really don't treat what bothers the patient day-to-day, their complaints are cough, breathlessness, and fatigue. So we are looking at sort of different variants on that. We're looking at breathlessness. We hit that in our Phase 2B. We are looking a responder analysis. We looking at clinically meaningful change in cough severity. So the hope would be that we can get a nice robust label coming out of that. So that will set us up nicely for payer discussions. Regulatory-wise, Jim, I'll let you comment? Yeah, we had a great discussion at the end of Phase 2 meeting on the patient report outcome. So cough severity NRS is our key secondary endpoint. FDA is very comfortable with significant change from baseline as being what's needed there for our approval or for a meaningful result. So I think that's really the key here is that we have that. As Jen mentioned, we also have other PROs in our hierarchy there. The other PRO that is important is a patient perception of cough frequency. Besides the objective cough count, we also have the patient perception, and we saw positive results there as well in the choral study. And one other dimension from a patient-reported perspective was, which is also in our key secondary endpoint, is that patients reported that they had improved breathlessness. We know that that's a very important aspect of the patient journey here. So the FDA agreed that that would be a meaningful key secondary endpoint as well. Okay, great. You know, I want to fast forward to potential approval and commercialization. So maybe broad strategy for a launch. What segments or centers would you be focused on, and how would you describe ability to reach patients? Yeah, so we're, you know, our first indication hopefully to get approval will be IPF. As Jim mentioned, just like clinically, we're out in all these IPF-ILD care centers. There's 90 of them in the U.S., so we're working with all them clinically. That'll also be our target commercially. And then beyond that, there's community pulmonologists who obviously write these scripts to about 10,000 targets there. So with about 50 to 100 reps, you can very effectively target this population. The nice thing about sort of the other ILDs, it's the exact same call point. So there's just a lot of synergy you can get at sort of, you know, this entire market, IPF and ILD, with that same 50 to 100 reps. RCC sort of changes that dynamic a bit. Okay, great. And there is a good portion of the IPF population not treated with antifibrotics. Maybe talk about the potential strategy to reach those patients. Maybe they failed. Maybe they're not on drug yet. It's somewhat, Judy, irrelevant to us because what these IPF docs talk about is when a patient gets diagnosed with IPF-ILD, they'll treat their fibrosis with an antifibrotic. Many patients drop because there's a lot of side effects, but they'll treat their cough. That's sort of a separate notion. So I think sort of on an antifibotic, not on an antfibrotic, we've already shown our drug works the same across all the different antif vibrotics. So for us, we're all about treating cough for that patient. Great. And I know you talked about this at the Annals, but we continue to get the question. I guess cough being a side effect of some of these, you know, next-gen antifibrotics? How do you think about that in terms of, you Know, the addressable population may be changing or not? Yeah, no, it's a good question. I mean, specifically, you're referring to diprostanil, which has had a cough problem. You know, I think, first of all, it is not approved now, so it won't be in our study. We have carved it out specifically in case there is any overlap. It will probably be something at some point. Either we will run the experiment or investigators will because we have heard from KOLs, that can be difficult to keep patients on. There's some hypothesis that because our drug will settle down hypersensitivity, maybe they'll be able to tolerate the drug better. So I think at the right time when that drug gets out and into the market, we'll do some separate work around seeing if maybe it's helpful in that arena. Okay, great. And just from your market research and early discussions, what were initial thoughts on how payers see the potential value of Paduvio, how could that translate into pricing? Yeah. So that's the nice thing about having IPF lead our strategy. It's a specialty strategy. Antifibrotics are priced quite high here, sort of $200,000 to $300,000. It is because it is a rare population, 140,000, and it is terminal. Most of them live three to five years. So the reality is payers are pretty clear it is category they don't particularly manage. We price tested off of our phase two data 75,000 to 125,000 a year, got really no pushback. So there will be some step edits in there, just like there are for anti-fibroids. You'll measure, you know, you'll manage it through a hub model, but I think we have a lot of room to move there in pricing. Okay, great. I want to make sure we touch on the other indications. So like you said, other ILDs beyond IPF, maybe just talk about the biologic rationale in those patients? How similar or different is the chronic cough in those other ILGs? Yeah, so we've had a lot of discussions with the KOL pulmonologists in this space, and basically the conclusion was that it's the underlying lung fibrosis that seems to be driving the cough. The difference between the populations is IPF is a little bit more pure as a respiratory disease. The other part of the population has other comorbidities associated with But the underlying assumption, which makes the trial relatively straightforward, is that you have underlying lung fibrosis, and that has been the underlying cause for the cough, and that's how we're going to treat the population. So we'll be looking at that and not really slicing and dicing beyond that. Okay, makes sense. And then you have an upcoming meeting with FDA. Maybe just talk to us a bit about key questions you'll be discussing with FDA in terms of Phase 2b3 design at your upcoming meeting. I think the key there is we're going to be talking about a protocol. We're going to try to be as aggressive as possible. So we'll discuss the options of that 2.3 or push it harder to see if we can get away with a single phase three, relying on the information that we generated with IPF and the discussions we've had with them. So I think, you know, the nature of the trial design, you know, the one trial, the duration, the end points are all going to be aligned with the IPF program, and obviously there's going to be a difference in the inclusion criteria, but not much in terms of, you know, we're going to rely on the fibrosis and cough. I think that's part of it and probably the bulk of it. We also need to talk about what is the path to approval here. This is going to be, you know, on top of and following the IPF lead, and so, you know, these are nicely synergistic, so we can gain a lot of information on safety and efficacy from IPF that will directly feed into this. So, what's it going to take to get approval here in terms of the size of the safety database and other things that are related to the approvability? So, that's really the focus of it. Okay. Great. We'll look forward to it. And then, like you referenced up front, RCC, very large opportunity. We saw GSK's program fail recently, making you certainly the leading program within chronic cough. Any potential read-throughs from the failure for your program and with potentially having the first FDA-approved therapy in your hands, has your thinking on commercial strategy changed at all given that failure? Yeah, no, it's a good question. It's a huge opportunity. We're sort of the only ones left here. It is hard to tell if there is read-thru because GSK really hasn't put out the data yet. We have sort of confirmed through investigator channels that placebo wasn't an issue, which I think is important for us. That was really the only piece of data that we would have had to think twice about. Commercially, I would say that that doesn't impact our strategy because we're going to be this IPF specialty-led company. The only caveat to that is Jim's going to be doing some formal dose ranging. Depending on where this dose ends up, there is a world where we end up in much lower doses in RCC, and that's a hypothesis. That's what we'll sort out in this next study. If we can end up in a low enough dose range, then we might have room to price per milligram and be able to maybe sort of get this therapy to a broader set of patients in RCC. So no, I would say nothing there. I think both Merck to what Jim said and Glaxo slash Bellis, they left behind good learning. We're sort of in that great, you know, fast follower mode where you get to not make all those same mistakes and hopefully get it over the finish line. Okay, great. And then maybe just a couple on your RCC trial wake. So you initiated the phase 2b there. Maybe just remind us of study design. Does the philosophy for trial design in RCC differ in any meaningful way from IPF? And then, you know, a key question we get on this program, just that sample size re-estimation, that's expected in fourth quarter. Just maybe walk us through that quickly. So the trial design, remember the river study which led us here, was a crossover design what's very common for that first study. This is really coral. This is our parallel arm study. Jen mentioned that we have three different active arms and placebo. We have a two-week titration period and a four-week fixed doses. So that's where we are. That's very similar to what we had with coral. In the RCC world, coming in prior, obviously, to the GSK news, there was this concern about how to manage placebo response. Maybe that still is a concern. But, you know, one of the things we learned from the KOLs is that it's important to put in some very important guardrails. So we have RCC that has to be diagnosed for a year for the patient. We're really watching carefully over the inclusion criteria for making sure we have the right RCC patient. And also, one other, the strategy that was proposed and actually used in the Bellis GSK design was a placebo run-in period. So we incorporated a placebo running period. This is really to mitigate individuals who may have more variable cough where they fall out. So, we have an entry criteria of 10 coughs per hour. We'll look at that at screening for eligibility and make sure that they still are above that at the end of the placebo run-in period. So those are the things that we're trying to do. Maybe that was effective if we learn more about the actual GSK data. But those are the things at the KOLs were really guiding us towards as we brought that program forward. And the sample size, are you going to go there? No, we get that question all the time too. Essentially we use it to make sure we can dial in the end. So we made certain assumptions. We assumed a 30% effect size. Again, we saw 56% in our 2A. We saw 36% in IPF. So we think we've been appropriately conservative. That's 100 patients, 25 per arm. But we do allow when half the patients finish dosing, an unblinded statistician outside of Trevi rechecks our powering assumptions. And we get one of three answers back. Either your powering assumption is fine, continue on. We're in this conditional power range where there might be a relative upsize here, which could go up to an additional 50 patients. That is just about dialing in the end or you're below this 40 percent power rate and we've deemed that futile for our experiment so it's a really good look halfway through the study to make sure you know in the olden days we used to overpower all these studies and not worry about missing it by a few patients now you can use some of these statistical tools to sort of dial in on that okay great and maybe just to round out the discussion remind us of cash runway what that covers within the operations that we've discussed today yeah so we have 306 million as of the last balance sheet day We had a nice raise in April, thanks to our Morgan Stanley bankers. So we're sitting in good shape. That will get us through an IPF approval. It'll get us though all of our ILD work, so that's good. It'll give us through this RCC study we're talking about. Doesn't fund the phase three trial in RCC. We'll have to sort out what that looks like. It funds pre-commercial work but does not fund any kind of commercial launch. So we guide into early 2030, but it gets us through all these data readouts. Okay, great. We're just about out of time, so thank you again for being here, guys. This was great. Thank you. Thanks. Great.