Greetings, welcome to the DURECT Corporation first quarter 2023 earnings call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Tim Papp, Chief Financial Officer. Thank you, Tim. You may begin. Good afternoon, welcome to DURECT Corporation's first quarter 2023 earnings conference call. This is Tim Papp, Chief Financial Officer of DURECT. Before we begin, I would like to remind you of our safe harbor statement. During the course of this call, we may make forward-looking statements regarding DURECT's products in development, expected product benefits, our development plans, future clinical trials, or projected financial results. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Further information regarding these and other risks can be found in our SEC filings, including our 10-K and 10-Qs under the heading Risk Factors. To begin, I would like to review our first quarter 2023 financial results. Our total revenues in the first quarter were $2.1 million, compared to $1.9 million for the prior year. This increase was due primarily to an increase in collaborative R&D revenue. R&D expense was $8.6 million for the first quarter, compared with $8.2 million for the prior year. The increases were primarily due to higher clinical trial expenses for our ongoing AFFIRM trial and contract manufacturing expenses for larsucosterol. For the first quarter, SG&A expenses were $4.1 million compared with $3.7 million for the prior year. This increase was primarily due to higher market research expenses, higher audit-related expenses, as well as higher employee expenses. As of March 31st, 2023, we had cash and investments of $44.4 million, as compared to $43.6 million at December 31st, 2022. We completed a registered direct offering in February 2023, raising $8.8 million in net proceeds. Excluding the proceeds from the financing, our cash burn in the first quarter was approximately $8 million. We believe our cash on hand is sufficient to fund operations into the first quarter of 2024. Lastly, I would like to highlight that we will be hosting a KOL event in New York City on May 16th. We are pleased to be hosting Dr. Paul Gaglio from the Columbia University Department of Medicine and Dr. Brett Fortune from the Albert Einstein College of Medicine, Department of Medicine, and Division of Hepatology. Dr. Gaglio and Dr. Fortune are both renowned hepatologists with a wealth of experience treating alcohol associated hepatitis, or AH. We look forward to hearing their insights about the current treatment paradigm for AH and the unmet medical need in this highly lethal disease. Several members of our leadership team will join Doctors Gaglio and Fortune to discuss the ongoing development and commercial landscape for larsucosterol in AH in advance of the top line readout from AFFIRM. You can find the details for the webcast of the event in our press release from April 27th on our website. Now I would like to turn the call over to our CEO, Jim Brown, for an update on certain of our programs. Thank you, Tim. Hello, everyone. Thank you for joining us today for our first quarter 2023 update. We're excited about the continued progress for our lead clinical program, larsucosterol, for the treatment of alcohol-associated hepatitis. 2023 is poised to be a significant year for DURECT as we look forward to completing our AFFIRM trial and reporting top line data by the end of the year. If successful, we believe AFFIRM has the potential to support an NDA filing. Our primary focus as a company remains gaining approval for larsucosterol in AH and bringing this potentially life-saving therapeutic to patients with no effective treatment options today. We are nearing our enrollment target of 300 patients in our phase IIB AFFIRM trial with more than 285 patients dosed to date. We continue to expect completion of enrollment by the end of this quarter. As a reminder, AFFIRM is a 300-patient, placebo-controlled, double-blind, multinational study with two active dosing arms and a placebo arm of 100 patients each. We're enrolling patients with severe AH, which are patients with MELD scores ranging from 21-30 and Maddrey's Discriminant Function scores greater than or equal to 32. The primary endpoint for AFFIRM is reduction in mortality or liver transplant at 90 days. We've enrolled patients in AFFIRM through a global network of clinical sites, including leading hospitals in the U.S., Australia, EU and the U.K. Our sites include renowned liver centers, we are working with some of the world's preeminent thought leaders in AH. The FDA has granted our larsucosterol AH program Fast Track designation, and we are hopeful that a positive result in AFFIRM could support an NDA filing. With this in mind, larsucosterol has the potential to be the first FDA-approved treatment for AH, where there is a substantial unmet need for these patients. We designed AFFIRM to be a potentially pivotal trial based on our phase II A data. In our open label phase II A trial, all 19 patients survived at 28 days, an encouraging result given that approximately 26% of hospitalized AH patients die within 28 days based on historical data. In April, we announced that our phase II A data had been published online by the American Journal of Gastroenterology. This peer-reviewed article includes cross-study comparisons with well-matched severe AH patients from a contemporaneous trial conducted by the Defeat Alcoholic Steatohepatitis or DASH Consortium. While the sample sizes were small and these patients were not part of a controlled study, these comparisons indicate that severe AH patients treated with either 30 milligrams or 90 milligrams of larsucosterol have statistically significantly lower Lille scores compared to the patients treated with the standard of care, including steroids. In addition, liver enzyme levels decreased rapidly in the larsucosterol-treated patients, including statistically significant reductions in ALT. We believe these results provide further evidence of the potential for larsucosterol as a treatment for AH. Our confidence that the AFFIRM trial will be successful is driven by our compelling phase 2A study data, including the recently published comparisons, the mechanism of action of larsucosterol, which ties directly into the biology of AH, and our multiple preclinical animal studies where we observed a profound survival benefit in multiple relevant acute organ injury models. I'd like to briefly turn to the market opportunity for AH. In addition to this high mortality rate, AH represents a significant cost to the US healthcare system, with over 150,000 hospitalizations attributed to AH at a cost of between $50,000-$150,000 each. As a result, larsucosterol represents a potential multi-billion dollar opportunity in the United States alone and could simultaneously provide substantial overall cost savings to the healthcare system. We will discuss the economic opportunity for larsucosterol further during our upcoming KOL event. We've begun to lay the groundwork for potentially commercializing larsucosterol in the US and believe we can effectively launch the product through a modestly sized hospital-focused sales force. We are also continuing to build awareness around the role of epigenetic regulators in acute diseases like AH. AH is also a global concern, allowing larsucosterol the potential to serve ex-US AH patients and their healthcare system. These ex-US markets represent additional attractive market opportunities. Because we enroll patients from a global site network, we believe a positive result from AFFIRM may support regulatory filings in the EMA and other regions. In summary, we continue to make great strides with AFFIRM and have enrolled more than 285 patients to date. We are on track to complete dosing the last patient in the AFFIRM trial this quarter, which would enable reporting of top-line results in the second half of this year. If successful, we believe AFFIRM has the potential to support an NDA filing. We'd now like to take any questions you may have. Thank you. We'll now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please, while we call for questions. Thank you. Our first question is from Kristen Kluska with Cantor Fitzgerald. Please proceed with your question. Hi. Good afternoon, everybody. Thanks so much for taking my questions. Sure. The first one I had is if you could break down for us this $50,000-$100,000 cost that you cited in your prepared remarks. I guess how much of this is just driven by the fact that patients are often in the hospital for a couple of days? Obviously I respect and understand the 90-day endpoint related to the FDA, but, you know, time to hospital, especially because in the two A, a number of your patients didn't even need that second dose. I guess, like how important are those statistics going to be for payer conversations should this drug be successful? A great question, Kristen. Thank you. It's good to hear from you. I'll start it, and then I'd like Keith to maybe speak a little further on this issue as well. I think we've seen from most of the literature that I've seen is your typical patient stay in the hospital is around six days for those that live and longer for those that don't. For those that live, it's about a $50,000 cost. For those that die in the hospital, it's $150,000. The majority of patients, if they're gonna pass away, actually, they move them out of the hospital to hospice care. Keith, do you wanna maybe speak some to the pharmacoeconomic drivers vis-a-vis hospitalization costs? Sure. Thanks for the question, Kristin. I think it's a good observation. I mean, the folks that are driving the higher end of that $150,000 cost, of course, are the ones that unfortunately expire and die while in hospital. This is taken from the HCUP NIS dataset. Our belief, and we're doing continued research in this, is that those are the patients that unfortunately take up the most amount of healthcare utilization as far as diagnostics, more intensive care unit time in hospital, length of stay. You had cited our phase two A study that showed that, you know, two-thirds of these severe patients only required 1 dose. However, that may be different in the AFFIRM trial. We'll be interpreting all of those results, length of stay, Time in ICU, time to a step-down unit, overall length of stay, and all of that will be important as we put together our value prop and budget impact models for the market access and payer environment. Thank you. Appreciate your thoughts there. A question we've been getting is just why do you believe that other mechanisms have failed in this space? What is it about larsucosterol's mechanism that might be more appropriate in this setting, especially with this recent paper and some of the deeper diligence you've conducted? That's a great question as well. I'll address it and then, and then we'll see if we have some more because we have both WeiQi and Norman on the line as well. I think first off, it's a complex disease. AH, unfortunately leads to the breakdown of a number of systems. These patients are eventually dying of multi-organ failure, so it's not just the liver. Eventually, most of them die actually from kidney disease. We've shown with larsucosterol that we protect against multi-organ failure, protect the kidneys, the liver, the lungs, and numerous models. We've shown shoring up, as it were, in protection of these organ systems in humans who have chronic kidney disease or chronic liver disease when we've dosed and we've seen reductions in the cytokeratin-18, these markers of cell death. If we look at drugs that have been tested against AH in the past, there have been two main areas of focus. One was in trying to reduce apoptosis. A couple of drugs have been tested there and unfortunately didn't work. There's also been drugs looking to block certain cascade of the inflammatory system with monoclonal antibodies. Those also were more one note and really couldn't address the breadth of the disease. With larsucosterol, we have a molecule that changes what we know has gone wrong. We know that there are elevations in DNMT or DNA methyltransferase levels in these patients. We know from patient data that there is hypermethylation ongoing, and we know a host of different systems within the cells are damaged. We know larsucosterol protects against mitochondrial membranes damage. We've got that component up. We know it reduces lipotoxicity, it reduces inflammation, enhances cell survival and regeneration of the cells, and increases autophagy. There's just a host of different components that have gone wrong that are addressed. Maybe I give it to... Maybe, WeiQi, you can start and then Norman maybe finish on this as well. Any additional thoughts? No, I think, Jim, you have covered quite well. I would also just add one more thing because alcohol, particularly in alcoholic, alcohol-associated hepatitis subjects, they do have impaired liver regeneration. Liver regeneration is very important in overcoming the acute liver injury and then re-resulting acute liver failure. Larsucosterol certainly promoting the liver regeneration, that's also important. Jim did mention that a little bit as well. Thank you. Norman? I have, pardon me. Too much to add to it. I was very impressed with the mitochondrial stabilization because mitochondrial dysfunction is a big part of the apoptosis pathway. I thought that was important. The, you know, steroids affect inflammation, but they also probably interfere with liver regeneration, as WeiQi pointed out. You need sort of this broad improvement without inhibiting liver regeneration in order to recover from this. I feel as if prior treatments have addressed one thing at a time, and what you need is something much broader than that. The mechanism of action is really impressive, but even more impressive is the empiric data that we saw in the phase IIA trial. Great. Well, thank you both. Great. Yeah. I think it is interesting when you see the histology of these patients. They aren't often biopsied, but sometimes there you do see mega mitochondria, so you know that there's a stress in that organelle anyway. Sorry. Okay. Thanks. For the second half of the year readout, just because we're getting really close now, do you anticipate that you would share certain endpoints first through a press release and then maybe save more detailed data for a medical presentation? What are your kind of preliminary thoughts on this, assuming that this plan goes to place with timing? Yeah. You know, it will depend on the timing. This is too important to wait, and we wouldn't. When we have the last patient enrolled, which we're getting close, obviously we know we're now over 285, so we just have just a few patients to go, a dozen or so left. When we enroll that last patient, we will announce that, and then people can start the countdown, so they'll know it'll be three months from then to last patient, last visit. Norman and the team have done a great job of keeping up with the patients as we've gone. We've been closing out centers as we can and closing out patients as we can. Our hope is that we'll just have those last, you know, 10 or so patients to, you know, to clean up as we get to the last few months. The team is hoping to have data within two months or so after last patient, last visit. That would be wonderful. I'm happy whenever it comes. One that day comes when we unblind the trial. We hope to report out with just a few days. That would be our objective. I'm sure we'll have a press release and I'm sure a conference call. I don't know about the timing of that versus meetings. We certainly wouldn't hold anything back at that point. I think we'll talk about it, eventually we'll present the data in more... in a broader fashion, you know, through publication and through meetings. Norman, do you wanna add anything to that? No, I think that's correct, Jim. Clearly we're as excited as anyone to unblind and see what the top line data on, you know, the most important things, then decide on a publication and presentation strategy. Great. Thanks. Look forward to seeing you in New York next week. Yes, absolutely. That's right, thank you for reminding me. Yeah, we do have our KO event next Tuesday in New York. Happy to have you guys over, and if not, online would be great. Thank you. Our next question is from Ed Arce with H.C. Wainwright. Please proceed with your question. Hi, Jim. Hi, everyone. Hey, Ed. Hi. Thanks for taking my questions. It's great to see you last week, and I also look forward to seeing you next week at your event. Beyond the timing of the trial, I just had a couple more questions. I think this would be important as investors start sharpening their pencils on this readout, is to just go over and explain why there were actually two... there are two dose arms in this study. Ultimately, if, you know, if both are positive and both are powered for statistical significance, you would seek to get both of them on the label. Then separately, the other question I had was just around commercialization. Given that this is potentially a pivotal study and you could be looking at, you know, an approval in the not too distant future, just wanted to get your thoughts on the hospitalization sales force, the MSL sales force, how you expect that to unroll given that there is a fairly concentrated, targeted set of call points. Thanks so much. Okay, sure, Ed. I'll start off and then I'll let WeiQi speak to a little more to the doses and then, and then we'll certainly have Keith speak to the commercialization post that. With regard to the doses, we are looking at two different doses, which allows us to gain a little more insight. It's basically we've seen pretty exciting results already in the phase 2A, with both of these doses. We've seen in various other human experiences, a variety of doses tested, and oftentimes the lower dose looks every bit good if not better than the higher, and that's also been the case in some of the non-clinical. It's, we certainly are excited to see what will come from this. As far as, dosing, WeiQi, any additional thoughts there? Those two doses were selected based on our understanding of the dose-response relationship in various magnetic studies, and also based on the ADME data in both animals and in human. On top of that, it was based on the PK data we obtained through the phase 2A study. That's how we determined these two doses should be in the optimum dose range of the drug exposure to the liver, because AH is a specifically liver-centric disease. That's how we selected these two doses. Although we know that the 150 milligram dose, that's the one we also used in the phase IIA study. That's the highest dose. It's also safe in these subjects. Nevertheless, 30 and the 90 milligram we selected moving to phase IIB are the, we believe, optimal dose range. I think that's a good point from a safety standpoint. In the NASH patients, we dosed for a month, as high as 600 milligrams a day. We certainly have given a huge amount more than these doses and for a much more extended period of time. Maybe I'll hand over the commercialization question to Keith, who, for those of you who don't know, has a tremendous commercial experience, in particular of late, before coming to DURECT at both Genentech and Pharmacyclics. He's sold a number of oncology products and has dealt with lethal disease before. We're excited for Keith and his team to take this on. Thanks, Jim. On Ed, your question of potential hospitalization sales force. We have been doing some preliminary work on just understanding the hepatology and gastroenterology marketplace, and the various hospitals and their discharge volumes in AH, working with big data houses that are well known, like IQVIA and Syneos and others. We know that there's a rough population of heps and gastros and advanced practice providers in the U.S. of about 5,000-6,000. We know there's around 4,000 hospital accounts, but only about half of those have had AH discharges of over 10 per year. We're starting to get down through the funnel on what that concentrated target list may look like, but we're still pretty early in the analysis. you know, I think we've talked about on previous calls, a sales force roughly somewhere between 50 and 100, I think would be ample to cover the United States for a rare disease, hospital-based disease like AH. We continue to work through on pace of what our commercial planning looks like. We'll talk a little bit more about that at next Tuesday's KOL event as well. We do have a pretty good understanding of where the targets may be and where those high volume tertiary liver transplant sites may be, and start to think about tiering structures and how that might influence the construction of a field sales force and commercial organization would look like. Great, Keith. Thanks for that. I appreciate it. I look forward to more details on Tuesday. One additional question, if I may, is just around the primary endpoint. Obviously, 90-day mortality and reduction in transplant. We know as you mentioned, Jim, that AH natural history is about 26% mortality rate at 28 days. Do you have any measures for the rate of transplants for AH patients? Great question, I'll let Norman speak to it a little bit after I'm done. Unfortunately, the bottom line is there aren't enough livers to go around. There are about 9,000 livers available for transplant in the United States across the entire country. We know there are 150,000 hospitalizations in 2020 for AH. We estimate that about 120,000 patients represent those 150,000 hospitalizations, with some coming back again. 120,000 patients, 9,000 transplants. They don't all go to AH. It's estimated that about half of those 9,000 transplanted livers go to people with alcohol-associated liver disease. The other half go to people who, remaining viral patients and inherited diseases like Wilson's and PSC and some obviously to NASH patients as well. You've got about half of those, about 4,500 going to patients with alcohol-associated liver disease. Somewhere between a half and a third of that remaining then 4,500 go to AH patients, which means you're talking about somewhere around 2,000 patients being, you know, having livers available to them out of 120,000. It's just that the numbers aren't there. I know Norman can speak much more eloquently than I can with regard to this. I don't know about eloquently, that is, as you know, it's a moving target because transplanting people for AH is a fairly recent development, it's sort of gaining in popularity. Previously, people didn't want to admit they were transplanting them because there was sort of this general feeling that you needed six months of sobriety. There was tremendous underreporting, and that was shown in a very nice paper by Brian Lee. Since then, there's been general acceptance. They're growing. Actually, UNOS has now created a special category for alcohol associated hepatitis. We'll get more accurate numbers going forward, but for right now, we don't know that exact number. As Jim said, we think... I think speaking to my colleagues, that it's approximately a third to a half of the people attributing, attribute it to alcohol, and alcohol makes up about half of the transplant volume of that 9,000 patients that got transplanted. Getting to the endpoint, it does obscure, the 26% and 30% you mentioned is sort of an all-comer. If you just take a general population of AH, you should expect a 30%. That's been shown in multiple studies. When you deal with a transplant center, they tend to see people in the higher ranges. The mortality of patients with a MELD of, say, 25, is more like 40%. You see higher mortality as you go up, as your admission MELD score goes up. Yeah. I would add also from a pharmacoeconomic standpoint, if we take a rough guesstimate of the n-number Norman just gave us, say it's close to 2,000. We know transplants can cost close to $1 million each. You're talking about, you know, somewhere in the range of about a $2 billion check that's being written for that piece. The other component, the hospitalization we think represents probably $7 billion-$8 billion as well. It's a substantial cost to the healthcare system, for sure. That's very helpful. Thank you so much. I know. Thanks. Sure. Thank you. Our next question is from François Brisebois with Oppenheimer. Please proceed with your question. All right, thanks. Taking the question, just a couple here. Just in terms of the inclusion criteria, just to touch on the MELD score and the severity. Can you remind us the difference between the phase IIA and the phase IIB in terms of severity of patients? Also, you know, from the cross comparisons, either with Louisville or DASH, can you also touch on the severity of those patients and I guess the implications of the changes in severity in the phase 2B. Thank you. Oh, sure. So straight up we're taking severe patients. These are patients in the AFFIRM trial that range in MELD from a 21 to 30, which match exactly with the severe patients we had in our phase IIA trial. To put that into some perspective, if you've got a MELD of 21, you've got about a 25%-26% maybe to a 30% chance of dying in the next 90 days. If you go to MELD of 30, it's 60%. As Norman says, in the mid-range, in the 24-25, it's 40%. It's obviously a huge problem. As far as the consortium goes, what we tried to do is pick patients who would have matched for our study. That was, that was the objective there, to get like and like. We had to have patients who, you know, we're doing a 28-day comparison, so they had to be alive at 28 days. We had to not count the DASH patients that died. There were a number that unfortunately died before 28 days that aren't counted in there because they don't have 28-day end zone data or you know, or score data at all. What we saw was their survivors versus ours, and all of ours survived. We still saw, to my eye, improvements in liver function and the like that looked like we had patients who were in a better space. I don't know, Norman or WeiQi, you guys any, anything to add? No. I think that accurately states it. When you, when you look at the, at the paper, remember that the patients in the DASH trial, the subjects in the DASH consortium had to survive at 28 days. Any patients who died prior to that were censored out of it. Even with that, you still see tremendous, you know, you see better survival. What's really impressive is how much their biochemistry was better, including their markers of liver injury, bilirubin and MELD scores. Well, MELD scores, it's a bit more complicated. Survival and bilirubin were significantly better. Great. Thank you. If I could just ask one last one. In terms of the comment to the previous answer about the doses used, is it fair to assume you don't necessarily expect a dose response here, correct? We might. I mean, we're doing the study to in order to determine that. We couldn't get enough information out of the small number of patients in the phase IIA. We're doing this trial to understand dose. I certainly hope we can distinguish between the two doses. I think it remains to be seen. I don't know. WeiQi, what would you say to that? Well, Actually, I think that's what Emil answered probably. right. Well, we'll have to see that, these two doses. Yeah. We just don't know. Yeah. Understood. I- All right. I'd be happy if either one wins, I'm really happy. I'll take either one or both. Yeah. Fair. Thank you. Thank you. Our next question is from Sean Kim with JonesTrading. Please proceed with your question. Hi, everyone. Thank Thank you for taking my questions. Hi, Sean. Hi. I just have a few questions, one on science and couple on commercial. I guess my first question is that, you know, based on your, you know, further analysis of the phase II A study, I'm just curious to hear your thoughts around, you know, some patients requiring second dose of prednisolone to see if there was any differences in terms of demographic characteristics of these patients or the ultimate clinical outcomes versus those who received only one dose. Kinda tying that into the commercial. If you think about, you know, potentially commercializing the product, you know, your thoughts around potential pricing, whether it'll be per dose basis or per treatment. Thank you. Sure. Well, I'll take it first and certainly ask WeiQi to comment as well, and then obviously Keith on the second. I think the first thing, it's important to note that just that we didn't have very many second doses, even in the severe patients, just a small number. Because it was the first testing of this drug in AH patients, I think early on we had some physicians who were keeping their patients in the hospital to enable a second dose, just thinking they want to give the drug its best chance, not really kinda considering the way it works. You know, this is outside of oncology, it's the first epigenetic modulator to be developed in medicine. The whole concept that only a single dose might reset my epigenome and allow my organs to improve is a very different way of approaching and thinking about medicine. The way I think about it, for what it's worth, I think about it a bit like a heart attack for the liver. You know, you've got a liver under extreme stress, but if one can get it over that acute stress circumstance, the liver does have great regenerative capacity, and this drug aids in that regard. I think it's all about shoring it up, shoring the other organs up. The body can begin to repair itself. WeiQi, what are your thoughts around the second dose? Yeah, just like Jim mentioned that epigenetic modulation typically, as we know, that the effect is relatively long-lasting, especially for an DNMT1 inhibition. The effect theoretically would be even longer lasting than DNMT 3A and 3B inhibition. larsucosterol inhibits all three, so the effect we expect will be much relatively longer lasting than anti-inflammatory agents or anti-cell death in agents, or just simply promoting the liver regeneration. Talking about the liver regeneration, another factor with the one or two doses is the liver is a very unique organ, it can regenerate. It would otherwise, once you help the liver to overcome the acute episode, they would regenerate and then hopefully would re-recover the acute episode. These are the reasons why we only selected one or two doses for this particular indication. Thank you, WeiQi. Now, Keith, maybe some thoughts around the one or two doses and commercialization. I know at this point, but we're a ways away from pricing, maybe you can just give us some general thoughts. Yeah, sure. It's a good question. I would say at this point, I would corroborate what Jim was saying. It's probably too early to say, although in our market access strategy meetings, this is certainly a topic of discussion. Obviously, the final decision is gonna be influenced heavily by the AFFIRM results and looking at the cohort of patients and their outcomes that had one or two doses. Having run a similar analysis on previous drugs, pre-launch drugs that I've worked on, I will say it is challenging for the for pricing on a per treatment course basis, as opposed to on a per dose basis. You run into various issues like ASP, best pricing and what have you, government discounts and the like. While we have not made any kind of determined decisions on that, it is something that we'll take into effect the AFFIRM results, and that will strongly, you know, have a, have a heavy influence, like I said, on how we think about overall pricing and on a per treatment course versus per dose pricing arrangement. Okay. That's helpful. Thank you. Just one more question on the commercial side. I guess you mentioned about 5,000-6,000 hepatologists and gastros. I was wondering how many of those doctors are currently aware of larsucosterol and epigenetic regulator program in general, and how much effort you believe needed to bring these physicians up to date on larsucosterol? That's a great question, and I think I'd let Norman start, and then I'll let Keith finish because I think it might have slightly different perspectives, so I'd love to, love to hear this one. Norman. Keith actually has data, so I'm just gonna say that among my colleagues, so, I sort of have lived in the academic hepatology world, which is a loose term for saying transplant centers. Among those colleagues, there is practically uniform knowledge of this trial. Keith has done a much more thorough job of looking at people sort of in what I would, not meaning to sound pejorative, but in sort of the next tier. Keith, I would like to, like you to take it from there. Yeah. We've conducted some market research in the US, looking at unaided recall of various products in AH. Obviously there aren't too many that are under development, and certainly the larsucosterol program is furthest along in 2B development. I would corroborate what Norman was saying. In those hospitals that are typically transplant centers or academic referral centers with multiple hep and gastro specialists that have a particular interest in alcohol, I think the recall, or, you know, the knowledge of our trial in larsucosterol is high. However, when you look at the entire population of about 5,000 to 6,000 that I quoted earlier, that's inclusive of anybody because this is not a disease that is, you know, typically referred to only a handful of sites or only a handful of sites have AH specialists. It's any hepatologist or gastroenterologist, they would have the training to treat AH. It is fairly spread out to our knowledge right now. When you get out of those tertiary care centers and specialty sites that are still seeing AH patients, the recall is gonna be a little bit lower. Therein lies the commercial opportunity and why we're trying to understand what the baseline of that now, particularly that's not too surprising given that there's nothing approved for AH and having worked in disease areas that have had little or no standard of care, in other fatal diseases like in oncology, hematology. You know, there may be a number of things under development, but, until you hit a randomized controlled clinical trial study endpoint, that doesn't really raise a flag for most people to start paying attention. I think if AFFIRM hits, later this year, as we've talked about, we certainly will, you know, have a big flag to raise with, that whole population of heps and gastros and advanced practice providers, and bring a lot of value to patients, and to the AH community. Great. Thank you very much. Thank you. There are no further questions at this time. I'd like to hand the floor back over to Jim Brown for any closing comments. Okay. I just want to thank you all for participating today. As always, you know, if you have any further questions, please follow up. We look forward to seeing hopefully a number of you in New York next Tuesday. Take care. See you soon. Bye. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.