Arena Pharmaceuticals, Inc.

Good day and thank you for standing by and welcome to the ARENA Pharmaceuticals 3rd Quarter 2021 Update Conference Call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone or touchtone key. If you require an operator assistance, please press star 0. I would now like to hand the conference over to your first speaker today, Vice President of Investor Relations and Corporate Communications, Patrick Malloy. Thank you. Please go ahead, sir.

Great. Thank you, Nika. Good afternoon, everyone. Thank you for joining us today. We'll get a chance to review the press release we issued this afternoon announcing our Q3 2021 financial results and key program updates. Joining me today on the call are Amit Munshi, our President and Chief Executive Officer, along with Lori Stelzer, our Executive Vice President and Chief Financial Officer. With regards to the format for today's call, in just a few moments, I'll hand the call over to Amit, who will make some opening comments, and then we will open up the call to a Q&A session. Before we begin, I would like to remind you that we'll be making some forward-looking statements today that involve risks and uncertainties about our goals, expectations, plans, beliefs, timing of events or future results, including those risks and uncertainties related to our pipeline, financial projections, and the COVID-19 pandemic. Forward-looking statements involve certain assumptions, risks, some of which may be beyond our control. All forward-looking statements are based on information currently available to ARENA, and we disclaim any obligation to update these forward-looking statements. A full description of these risks can be found on in our earnings press release and our latest SEC disclosure documents. Now, I'd like to turn the call over to Amit Munshi. Amit?

Thanks, Pat, and I hope everyone's got a chance to review the press release, and thanks for everyone being on the call today. So, let's jump right into Q&A. Okay.

As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question or if your question has been answered, press the pound or hash key. Your first question comes from the line of Nina with Rita Garg from Siri. Your line is now open.

Hi. Thanks, guys, for taking my question. This is Dina on for Nina. Our first question, and if maybe we can squeeze in a second, would be, can you just share any additional details on the baseline characteristics for the Elevate UC studies in terms of how they compare to OASIS? In particular, the commentary on baseline disease severity and previous, you know, anti-enterogen use versus OASIS. That would be very helpful.

Great. Thank you. So two quick comments and two things we've disclosed publicly. Number one, the overall characteristics are very similar to OASIS, with one exception. In the OASIS study, we had 60% of patients who were naive and 40% who were pretreated. Elevate 52 is running about 70%, 30%. And UC12 is running about 60-40. So they're both in the range, but won't be, you know, naturally won't be exactly the same. So that's the only notable difference is we have more naive patients in the Elevate52 trial. Other than that, everything is what best.

Your next question comes from the line of Alicia Young from Canthar Fitzgerald. Your line is now open.

Hi, this is Emily on for Aletheia. Thanks for taking our questions. I was just curious about your thoughts on the read-through from the Elevate UC studies in 1Q22, if those come out positive. Would that kind of increase your confidence going into the Crohn's data readout in the second quarter? And I guess just any thoughts around that. Thank you.

Sure. I mean, look, there are two separate diseases. And there are two separate study designs. One's a large-scale clinical, large-scale phase three trial, you know, very robust in size. And naturally, from a disease mechanism and action perspective, it increases our confidence that UC will be, or Crohn's will be successful. But again, keeping in mind all the caveats that the Crohn's study is a 70-patient, two-dose, no placebo control trial. trial. So with the caveats of the trial differences, we would naturally expect our confidence to go up.

Okay, your next question comes from the line of Ya and Suneha from Guggenheim Partners. Your line is now open.

Hey, guys. Thank you for taking my question. I love the format that we just straight go into the Q&A. So two for me. One is, so you are using a treat through design, which obviously facilitate the comparison with the gold standard Remicade, right? But how does this trial affect the comparison from Orzanimod? So that's first question. The second is regarding the placebo rate. You know, if you look at the remission rate specifically in the induction phase, the placebo rate tend to be But for naive patients, we have seen placebo rate in the 15% to 16% range. And given that you have 60% to 70% of patients that are naive, how should we think about the placebo rate for both studies? And then what is actually embedded in these studies to reduce the risk of higher placebo responses? Thank you.

Yeah, thanks, Jeff. And so let me take the second question first, and then we'll come back to the second. The first part, so the placebo rates are in a pretty narrow band across all the comparative trials. And you're right, the placebo rates are higher in the naive and lower in the pre-treated patients. And that's consistent between our OASIS trials, consistent across most of the trials that are out there. So we don't anticipate placebo rates being dramatically different than what's been seen historically. If you recall, the Ozonamod trial was, I think, about a 70-30 split. Ours is a 70-30 split. Between 70-30 and 60-40, you're not going to see a huge variation, at least based on historical evidence. As far as the treat-through design, you're correct. It gives us a much clearer point of view between both the two main products used in ulcerative colitis, Remicade and Humira. And we think that that's really the important discussion to have. We also chose that design for a couple other reasons, which we've discussed historically. But most importantly, it's a real-life example of how the drugs will work. And in the rural world, you don't get to re-randomize just your responders. And importantly, there are some ways to do some cross-trial comparisons. There are some published methodologies, and we'll be doing some of that work when we disclose the data so that you as the analyst community, as well as the investor community, can begin to take a look at how a TRASMOD stacks up. So we'll do some arithmetic to kind of help people out with all the caveats of cross-trial comparisons. But we really think that the treat-through study design is a superior design simply because it mimics real-world treatment.

Your next question comes from the line of Jason Gerberry from Bank of America. Your line is now open.

Hey, good afternoon. This is Chi on for Jason. Thank you for taking our questions. I guess two from me this afternoon. I guess first one on clinical trial progression, given COVID has remained somewhat of a fluid situation with the new variant and whatnot. Curious if you can provide any commentary on overall clinical trial progression. Is everything on track in terms of enrollment and data collection? And I guess if you can confirm there isn't any new repeated or like new signals and alarming lymphopenia or any protocol violation like what you've seen with the atopic derm phase two study, that will be helpful. I guess my second question is curious if management has any thoughts or commentary on the early commercial launch of Ozonamide in UC, whether you see there's any read-across you can draw to etrosomal, whether it is physician's appetite or market opportunity for the S1P class. Thank you.

Thanks, Chi. So, in terms of study conduct, no change from the commentary we had over the last couple of quarters. Everything remains on track. Our discontinuation rates, dose interruptions, all of that is well below our preplanned statistical expectations, so we're very pleased with study conduct across the board. As far as Ozonamod is concerned, it's still early days. We have a couple of data points suggesting that things are looking pretty good and there's good appetite for a once-a-day oral without the warnings that the JAK inhibitors clearly have. And so we're pleased with the early read, but again, it's very, very early, and I caution anybody into reading too much into this juncture. I'll also remind everybody that OzonMod's priced at a significant premium to other products in the category, but the early data seems encouraging. But again, with all the caveats, it's super early. I think a couple of quarters from now, we'll have some more data points, and we'll be able to understand exactly what's going on. It's also early in the reimbursement cycle, and As you know, it takes a while to get broad coverage of compounds and make sure that they're available to patients. And so, again, we'll be monitoring and tracking all of that. We'll continue to provide additional commentary on this as more data points become available.

Your next question comes from the line of Chris Shibutani from Goldman Sachs. Your line is now open.

Great. Thank you very much. Couple questions. Over the past quarter, we've seen some other mechanisms and drugs have various experiences from a data as well as regulatory standpoint. Amit, you referenced the issue that the FDA has with the JAX. I'm curious to know what your perceptions are of that and nuanced views in terms of how that might guide how you're thinking about your own regulatory approach. And then the TIK2 data from Bristol was, at the lower dose, a surprising disappointment. Curious to know your take there. That would be my first question, perhaps, if you could address that.

Sure, Chris. Yeah, I mean, look, there's multiple modalities in clinical development, both biologics and then other versions of the JAK inhibitors, including the TIK2 inhibitors. Our real take is There's a tremendous market need for a once-a-day oral. Without a black box, it's got a safe, durable effect, one that does not take tremendous monitoring and ongoing monitoring of patients over time. Without black box for malignancies and thromboembolic events and all the other things that we've seen to date. So we remain confident the profile of atrazomib has a position to be potentially the gold standard in terms of where it could end up in the treatment paradigm. So, again, it's a once-a-day oral, and I emphasize oral because we get a lot of questions around many of the other biologic-type approaches that are being developed, and single-cytokine inhibitors, for example, and we'll remind everybody that. the disease is more complex than a single cytokine. And being able to affect the disease pathology at the right point in its physiology is really, really important. And we think we're kind of navigating the sweet spot here with the TrasMod. So we remain confident that we've got the right profile coming out of phase two and hope to replicate that in phase three. And sorry, what was the second part of the question?

I think it would be decrevacitinib and the TIK2.

Oh, yeah, so the TIK2. And, you know, we've said for quite some time that the TIK2 agents are still working on the JAK-STAT pathway. And, you know, as they increase the dose, they'll continue to see a side effect profile that we think will be consistent with the JAK inhibitors. As you guys know well, we've been talking about this for going on three or three and a half years now. And our prognostications in terms of what's going on with the biology have been fairly spot on, I think. And using a very low-dose JAK or using a low-dose agent in the JAK staff pathway, whether it's a JAK1, JAK1.3, 1.2.3, whatever specificity you talk about, or even the TIK2, we're going to see some of the same profile. So again, we come back to the fact that once a day, oral agent without the liability of the JAK inhibitors has the opportunity to be very significant in terms of the treatment of the disease.

Okay, your next question comes from the line of Chris Howerton from Jefferies. Your line is now open.

Great. Thank you very much for taking the question. I guess mine is pretty simple. Obviously, you have $0.8 billion of cash on the balance sheet now, but pretty significant burn as you finalize the clinical trials. So do you anticipate having sufficient cash to commercialize a Trasomod assuming success?

Well, let me hand that off to our CFO, Lori, who's on the call. Lori?

Yeah, hi there. So our cash burn has been about $120, $125 million a quarter. And we haven't given forward guidance as to cash burn, but we can expect that with the UC Phase III rolling off some decline in costs there. And that would be offset by the start of AD Phase 3 and some of the early commercial builds. So we feel very good about the cash position with a little over $800 million. And, you know, hopefully with the finalization of the budget and positive UC data, we'll be able to give some forward cash guidance at that time.

Okay, cool. Thanks, Lori. And, Ahmed, if I may, for the – I just don't remember seeing this before for the Tumana Grill Phase 2 for Raynaud's phenomenon. Could you tell us a little bit more about that opportunity? What is that exactly?

Sure. So, as you know, our agents have multiple potential indications. Even our two cardiovascular agents have quite a few different places they can go in terms of disease pathologies. As we all know, Biology is quite conserved across various disease states, so you can follow some of that biology. In this case, we believe that serotonin plays a major role in this condition. Specifically, we're not secondary to systemic sclerosis. And, you know, it's really quite striking. There's quite a significant prevalence of these patients, so almost 200,000 patients with Renaud secondary to systemic sclerosis. So given that the disease pathology is spot on, given that you can actually look at an outcome measure that's quantitative in nature, in this case we're using infrared thermography, we think there's a really interesting opportunity here to explore with a compound that's already in-house and already under already working in another Phase II indication, already progressing in another Phase II indication. So, again, continue to expand the broad utility of these fantastic compounds that we have. So we're excited about it, and we're excited to get that study up and running.

Your next question comes from the line of Joseph Schwartz from SZB Learing. Your line is now open. Thank you.

Hi, thanks very much. I was wondering if you can give us any insight into how the geographical distribution of patients who've been enrolled in Elevate 12 and 52 compares to each other and also other studies in UC and if this could skew the results in any direction based on differences in the way clinicians or patients behave or account for disease activity.

Sure. So I'd answer that two different ways, Joe. First is you know, it's really the same clinical sites that move from one study to the other. So, you know, if we were ever able to get a detailed breakdown of clinical sites for Ozonamide, for example, and then R12 and 52, and we drew a Venn diagram, you'd see a very, very substantial overlap on clinical sites. There's only so many clinical sites that can work in this area. That's number one. Number two, endoscopies are centrally read. And that helps with the heterogeneity. You know, way back in the day, you know, a decade ago, two decades ago, a lot of the endoscopies were read locally, and that created a lot of noise in the data. So to standardize, again, this is going back a decade plus, that we've moved to centralized endoscopy readings to eliminate a lot of that geographic variability.

Your next question comes from the line of Jessica Fee from J.P. Morgan. Your line is now open.

Hey, guys. Thanks for taking my questions, too. I was hoping if you could just talk about specifically what is thought to make a TRASMOD more efficacious than a Xanamod. I think the differentiated safety is more clear, but can you just remind us of the, just basically how you think you were able to show such a stronger efficacy result in Phase II? And the second question is thinking ahead to what you could learn from study A in Crohn's, how clear of an indication do you expect to get from this study on which dose to move forward with? Or maybe put differently, how likely do you think it is that these doses end up looking truly different from each other?

Yeah, so on the first part, I think it goes back to the history of the compounds. you know, to refresh everyone's memory. Ozonavod was a tool compound that Scripps did not go through a formal medicinal chemistry program in the same way that Etrasimod did over a decade ago. I'll remind everyone we don't just have a TRASMOD, we've got libraries of S1P modulators and some of the most important SAR work that was done on the receptor on these compounds was done at ARENA. So we're the beneficiaries of the fantastic chemistry that was done historically. And the implications of that are multiple fold. Number one is not only do we not have the titration schedule, we've got the lowest intrinsic heart rate effect, but from an efficacy perspective, the ability to to profoundly affect dendritic cells, for example, we think plays a role via the S1P1 and the P4 axis. And we think those are the kinds of things that really begin to differentiate on efficacy. The last point I'll make on efficacy is something that we're exploring in even more detail, and we'll continue to do this over time. It has to do with barrier function. And all the diseases we're talking about, whether it's UC or Crohn's or atopic derm or barrier dysfunction conditions, And we know from the literature, and it's been well known and characterized over a long period of time, that S1P1 plays a role in closing the junctional proteins involved in these diseases. and really closing these barriers, we know that S1P2 actually does the opposite, actually opens those barrier functions. And in our hands, when we publish this data, there is an indication that Ozonamide hits the S1P2 axis, and that would, again, work against itself in a sense. So we think the combination of the fact that it's a It's just a cleaner, better compound that's gone through some very rigorous medicinal chemistry over a decade at ARENA. The activity on the dendritic cells we think is a major contributor, and we'll continue to do a lot of work to elucidate that even further. And as I mentioned, we're doing a significant amount of work on barrier function. We think that's going to be an important thesis that the scientific community is very intrigued with, and it has to do with... this activity on S1P1, closing cell-cell junctional proteins in S1P2. As far as looking at 3 milligrams versus 2 milligrams in the TRASMOD phase 2A study, or study A in Crohn's disease, we really don't know. It's early days. We haven't really explored 3 milligrams in the patient population. We know that 3 milligrams drives about 15%. uh increase in um mean lymphocyte reductions um compared to two milligrams so it's it's not a it's not a linear step so for example two milligrams drives about a 50 increase over one milligram five zero and three milligrams about 15 so we don't know how that's going to translate in the clinic in Crohn's, and that's what we're hoping to find out here. The heterogeneity of Crohn's, the severity of Crohn's makes it the right condition to really explore the higher dose.

Your next question comes from the line of Kenan McKay from RBC Capital and Markets. Your line is now open.

Hi. Thanks for taking the question. Maybe on the Elevate trials, just wondering if you can help us contextualize what kind of impacts we should think about from the COVID-19 pandemic as it relates to, you know, potential missed patient visits or censoring of, for instance, an endpoint. Is there anything built into the trial to potentially make up visits or ensure data collection there. And then second to that, I was wondering if the team could comment on some of the commercial work you've been doing. This is something I've been thinking about since your UC KOL event. Just wondering if you can there sort of contextualize really what a TRASMOD is bringing to the table beyond Ozanamod as it relates to some of your conversations with them. with clinicians, really just trying to, again, understand how much this can expand the market versus what is Animobs doing in UC. Thank you.

Sure. So coming back to the, starting with the phase three Elevate trial, when you design these trials, as you guys well know, you have preplanned expectations that you work in in terms of dose discontinuations or study interruptions or patients dropping off. And we're really pleased that through the pandemic, our very rigorous process in terms of tracking these patients has allowed us to keep those rates below our preplanned statistical expectations. So that's really the metric that we pay attention to, which is, you know, we've seen things that are not what we had forecasted ahead of time, and I'm really pleased to say we are not. So overall study conduct has continued. As I've mentioned before publicly, when the pandemic hit, We went to a very, very hands-on manual process where we tracked every patient, every site, every day, every visit around the world at every site in every country. And to ensure that patients, you know, got their medications, were compliant in terms of their diary inputs, and were compliant in terms of their – their endoscopy and making sure patients could get to their endoscopies, making sure the sites were active in terms of being able to perform the endoscopies. That was all work we put into place right at the beginning of the pandemic, and I think that's paid dividends in terms of the discontinuations and dropouts being below our preplanned statistical expectations. In terms of the commercialization of the product, I think there's sort of three ways to think, three different levels to think about our commercial readiness. Number one, of course, we think the compound has some intrinsic features that are dramatically different. A much faster on rate, the absence of a titration schedule, the lowest first dose heart rate effect. We haven't seen consistent changes in LFT as Ozonamide has. And then most notably, what's the most important for clinicians from all of our quantitative research is the off rate. When you withdraw the drug, 100% of patients are back to baseline lymphocytes within a week by label. You have to wait 90 days to introduce another immunomodulatory agent for, after ozonamide. So we think that makes a trasmod very different intrinsically. And those are intrinsic features that have to do with the physicians having a certain level of control. So all of that will translate into the eventual label, as we hope. And that'll give us a foundation for a differentiated product from ozonamide. So that's number one. And again, coming back to the quantitative research, it comes back to these points over and over and over. Number two is really the work we're doing with Gladiator study. It's a landmark study. Nobody's ever studied this more moderate patient group. We think having that data, it's a PERI approval study. We expect to have that data post-approval. We think that expands the market quite dramatically. There are literally hundreds of thousands of patients who have active disease but don't meet the criteria for advanced line agents today. We have tremendous amount of excitement in the investigator and the KOL community about this study, and we think that will be a game changer in terms of how the product is adopted in the marketplace. And the final piece I'll add is, We're not leaving a lot of things to chance in terms of payer uptake. We're spending a lot of time with payers now. We're working with payer data using real-world evidence, using an outside vendor who can evaluate this data, understand the cost structures, understand where the costs reside in these payer groups, whether they're straight-up payers or they're integrated delivery systems. and help them understand exactly when and how to intercede in the disease pathway with the Trasomod. So, we think that will pay huge dividends in terms of our ability to get rapid uptake in the payer community. So, you know, as most of you know, we began building out commercial infrastructure very early. We began building these platforms out very early, much earlier than companies our size traditionally do, and we've had the the privilege of having the balance sheet to be able to do that. But that's all toward having a line of sight into commercial success. So it's not enough to just have great phase three data. It's not enough to get a drug approved. But none of this matters until patients actually receive the drug. And that's the most important thing for us. And so, again, that work began a couple years back with thinking about the gladiator study, with the work we're doing with payers. We've also had – over 50 medical science liaisons on the ground, working with clinical sites and KOLs for over two years now. So these are all things that, you know, don't get a lot of attention today because the focus is on the phase three data endpoint, and I understand that from an investor perspective. But if you don't make these investments early, you know, you could run into substandard launches later on. So I think that's super important from our point of view is to really kind of aim past the target, make sure we're We're getting the work done now in order to make sure we have commercial success on the back end.

Your next question comes from the line of Joseph Stringer from Needham and Company. Your line is now open.

Hi, everyone. Thanks for taking our question. Our question is on the Cultivate sub-study A, understanding the increased number of patients from 50 to 70. one of your thoughts on your confidence level, at least based on your design here to increase it, I guess, assuming favorable results, would there be any scenario in which that would not allow you to go directly to a registrational trial? For example, if you would need to increase the number of patients further or run an additional study, just trying to think about the scenarios there. And then For the alopecia areata results second half of next year, would you include data from the 3MIG cohort in that one? Thanks for taking our questions.

Yeah, so on Crohn's, as we discussed before, Ozonamide had approximately 70 patients in their study. The upatacitinib phase two study was approximately 70 patients. We think that's sufficient to see a clinical signal and allow us to move to a registrational program. Naturally, the quality of the data there will be important, and as will our regulatory interactions. But the fact that there's clear precedent that a database of that size on top of a UC database in terms of total safety for the GI community and for the, I'm sorry, the GI regulators, and being able to see a meaningful clinical signal is sufficient to move to a registrational trial. So that's really been our focus and working off of, you know, precedents, really. If we think about the alpusha areata study, we did that through milligrams. Again, AA is a much more difficult to treat disease than atopic therm. Just like Crohn's is a more difficult to treat disease than ulcerative colitis. And so we thought the risk benefit to add three milligrams was important there. Again, we don't have data from three milligrams in any patient group, only in healthies. And so we'll see the Crohn's data first at three milligrams. We'll be looking for a dose response there. And then similarly, we're looking for the same thing in the AA study.

Your next question comes from the line of Jason Butler from JMP Securities. Your line is now open.

Hi. Thanks for taking the questions. I'm just wondering if you could give us an update on the VOYAGE trial in EOE and also any perspectives on the evolving treatment landscape given the recent data for Dupixen. Are you also looking to enroll severe patients into VOYAGE? Thanks.

Yeah, so I think the patient makeup will be similar to what we've seen in other trials, whether it's the Ciglicate antibody or Capixin. And again, if we're able to accomplish what those agents accomplish, but we're able to do the once-a-day oral, we think that's a substantial game changer. Capixin's a fantastic drug. It has... meaningful effects across multiple different agents. We know that most of these diseases are not pure Th2 diseases. There's Th1 activity. Th1 cytokines are active in the chronic phase of these diseases. And unlike some of these agents, we're hitting multiple parts of the disease process. Also, I'll just remind everybody that on histology, you don't just see eosinophils. You see CD4, CD8, CD4 positive, CD8 positive T-lipocytes. You see a variety of other cell types, including dendritic cells, as well as mast cells. So, and we've demonstrated activity against all of those cell types in multiple models, as well as human histology. So, we think we're, again, we're following the biology based based on everything we know today, based on all the work we've done over the last decade. And we think having a once-a-day oral in that population could be a significant game-changer. And the patient population makeups are consistent across most of these trials.

Your next question comes from the line of Patrick Trucayo from HC Wingright. Your line is now open.

Thank you so much for taking my question. I'm Jason Shea. I'm speaking for Patrick. And I have two very quick questions. So my first question is, will the NDA be filed before or after the data from Gladiator is available? And if before, would there be a need for supplemental NDA filing to include the details from Gladiator program? And my second question is, can you discuss ARENA's business development strategy going forward and how the strategy could change, if all assuming a positive outcome on the Elevate program next quarter? Thank you.

Sure. So the Gladiator study is a peri-approval study. It's designed to read out after the approval, so well past the NDA after the approval, and would look for opportunities to include that in the clinical experience section of the label at that time. The data is really designed for the clinician community as well as for the payers to That's really the context of the Gladiator study. And we'll assess that as we get closer and as we get through approval and we see the Gladiator study, we'll have to make some decisions about how aggressive we go after that patient population in terms of additional studies and maybe even supplemental NDA. But again, just to refresh, we won't have that data until after approval. The business development, as you know, we recently did a transaction with Ayers Therapeutics. We're very excited about that. We think it adds another leg of the stool for the company, potentially, and two dermatologic conditions, PPP and HS, as well as potentially an IBD. And we think that'll continue to build out our portfolio over time. We have a very rigorous BD process. We, before getting to Airstale, we looked at over 200 opportunities over the last three years. We wanted programs that had novel biology. We thought things that fit our therapeutic area are important. And we really put an emphasis on the quality of the compounds and the quality of the chemistry. So there's just not that many of those things that are out there. But we continue to scan. We'll continue to be as rigorous post elevate data as we are today in thinking about how we build out our pipeline over time.

Your next question comes from the line of David Wong from SMBC. Your line is now open.

Hey, thanks so much for taking the question. So I just wanted to get a little bit refreshed on the Aristea asset, which you in-licensed In terms of our expectations for the development path of that asset, when should we be thinking about seeing some of the first data from PPP and any other comments on other indications you might pursue with that asset?

Sure. So, we're looking at three indications there, a phase 2B in PPP and a phase 2A in both HS as well as potentially in recalcitrant IBD patients that have more neutrophilic disease. Again, The rigor at which we approach business development is substantial, and we spend a lot of time thinking about finding the right compounds with the right chemistry, the right pedigree. That's really important to us in terms of where these compounds come from, how much medicinal chemistry work has been done, how well characterized are they. And the Airsta team had done a fantastic job with this compound that originated at AstraZeneca. And so we're extremely excited about the collaboration. Pat, correct me if I'm wrong, but I don't believe we've disclosed any timing for any of those clinical milestones at this point.

Correct. No, we have not disclosed anything.

But we will over as we move forward in time provide some more context in terms of when those clinical data readouts will look like. Having another phase two asset with potentially three indications in our portfolio allows us to continue to build the company both in terms of compounds, in terms of market opportunity, but also in terms of key data readouts and catalysts that will be on the UC data.

Your next question comes from the line of Prakhar Agarwal from Jones Trading. Your line is now open.

Hi. Thanks for taking my question. Firstly, on the treat-through design in UC, Humira and Remicade have produced slightly diverging results in the maintenance phase versus induction. Humira clinical remission on a placebo-adjusted basis increased slightly in maintenance relative to induction, but Remicade actually decreased in the maintenance phase. So my question is whether Humira treat-through trial is the right comparator or Remicade trial for UC52. And secondly, on the Phase III ADEM trial, Do you plan to include Dupixent refractory patients also, and whether rescue therapies be allowed in the phase three maltherapy trial? And just as a follow-up, if you can confirm that the trial is still on track for initiation by year end. Thank you.

Yeah, so yes, we will have a small proportion of Dupixent. Remember, Dupixent is only penetrated about four to five percent of the AD market, so we wouldn't anticipate seeing a lot of Dupixent refractory patients in that study, and the study is on track to initiate by the end of the year with first patients involving the first part of next year. Coming back to the treat-through study design, I think this is always the challenge of cross-trial comparisons, and not just cross-trial comparisons, but cross-trial comparisons that might be separated by 10 years temporarily. So you have to take that with a tremendous degree to solve. The patient demographics in Remicade, when it was first developed, remember there were no other biologics approved in the space, and so they had 100% naive patients. Humira had a slightly different situation. So, you know, this is always a challenge across our comparisons, especially when they're separated by upwards of a decade temporally. And so I caution you in making any comparisons comparisons at this time. At this point, I think we have to take the data on its own merits, understanding today's treatment paradigm and today's treatment patterns, and understand where the unmet need is today in those patients. As you also know, Remicade has a far higher rate of neutralizing antibodies. That plays a pretty big role. We know Humira has a pretty substantial drop-off in effect. We know a substantial portion of patients that, between six and nine months, either doubled the dose or doubled the intensity of Humira treatment. We think that's also largely due, in part, to neutralizing antibodies. So, with a small molecule, you don't have that. So, again, different modalities, different time points, different structures. And we'll spend more time talking about this as we get to the data.

There are no further questions at this time. I'll turn it over back to Patrick Malloy.

Great. Well, thank you, everybody, for joining us on today's call. And with that, we'll look forward to speaking with you next after the first of the year. So thanks very much, everybody, and enjoy the rest of the day.

This concludes today's conference call. Thank you for participating. You may now disconnect.