Good afternoon, everyone. Welcome. My name's Lucy. I'm an associate on the JP Morgan Health Care team. I have here with me Aclaris Therapeutics. I'm very honored to introduce to you the CEO, Doug. We also have with us the CSO, Joe. We also have with us on stage the CMO, Gail. We also have the CFO, Kevin, with us. All right, I'll leave things to you, Doug. Great. Thank you, Lucy, and thank you to JPM for the kind invitation. I'm sure you all feel it's great to be seeing people in three dimensions again. You all look great in two dimensions on Zoom, but it's a lot more fun when you can interact with people directly, so thrilled that that's the case. I've been CEO only since last week, but I am honored to speak on behalf of the 100 employees of Aclaris Therapeutics and to share our story with you. The slide deck that I'm presenting has been posted to our website, so you don't need to madly write down notes. You can just access it that way. When you do so, by all means, do read our cautionary note on forward-looking statements and take heed of it. All right. Who are we? What do we do? We're, as I mentioned, a 100-person company. We're based in Wayne, Pennsylvania. We've been around for about 10 years. We actually started as a derm and spec pharma play, founded by my predecessor, Neal Walker, who's now the Chairman of the Board, and our former CFO, Frank Ruffo. In the mid-2010s, they began interacting with a really interesting group of scientists, formerly of Pfizer, in St. Louis called Confluence Discovery Technologies, and they were working on a topical soft JAK. In 2017, they had the good idea of actually purchasing Confluence, and by so doing, acquired a world-class discovery engine that it basically is the source of a very, very good pipeline that I think is the envy of most of the companies that are our size. Our secret sauce is really kind of threefold. One of them is around the expertise of our scientists, led by our CSO, Joe, who is the head of Confluence and is now, you know, leading those efforts there. We've added more recently a world-class development capability led by our CMO, Gail Cawkwell, a card-carrying rheumatologist. Our friends in St. Louis have a proprietary platform called KINect, which basically allows us to explore and exploit the kinome in creative ways that are different than pretty much everybody else. The result of that has been six candidates nominated for IND enablement over the last five years, with four drugs actually getting through to IND and three of them being in active dosing in the clinic. Why go after the kinome? This is a very target-rich area of human pathophysiology. You can see on the left-hand side of the slide, there are over 30 drugs that are using kinase-based mechanisms to treat either oncologic or immuno-inflammatory diseases. These drugs, many of whom are mega blockbusters, accumulate up to about $50 billion a year in annual sales. That is great, but the human kinome is large. Excuse me. There's over 500 proteins in it, and 90% of them have not been targeted yet. There's a tremendous substrate here for us to be exploring, but one has to do that in a way that's more clever than others. The way we've done this, again, using the KINect platform, is we have multiple different programs, and each of those programs have resulted in one or more drugs getting through IND enablement and into the clinic. The first approach is to find novel ways to target the MK2 pathway, which is a sub-pathway of P38, which I'll explain in a few minutes. We have two offerings in that space. Zunsemetinib, also known as ATI-450, is in phase II-A and II-B development currently. We also have a drug, ATI-2231, which is chemically proximate to it, that is about to be an IND file that we should be dosing patients relatively soon. The second program, it's what we call tissue-restricted JAK inhibitors. The premise there would be to get the efficacy of JAK inhibitors either in dermatologic conditions or GI conditions, but in such a way as you don't get systemic exposure and are thus not privy to the safety concerns that one sees with JAK that has resulted in fairly onerous negative labeling for them. The third is to take an approach to ITK using covalent chemistry that allows us to capitalize on that pathway. Those three programs have resulted in this current pipeline. ATI-450 is in active phase II development. Our largest study is a phase II-B study in rheumatoid arthritis, but we also have phase II-A studies in hidradenitis suppurativa, which I'll call HS for the rest of the presentation, and in psoriatic arthritis. Our ATI-1777 is a topical soft JAK that we initially engaged Confluence for. It is being developed for atopic dermatitis with a phase II-B readout this calendar year. Rounding out the field in terms of clinical assets is ATI-2138. It is an ITK/JAK3. It's much harder on ITK. It activates ITK much more than JAK3. It just completed an SAD study for which we reported data late last year. Just this week, we began dosing of the first cohort in the MAD. In the immunoinflammatory space, we also have a gut bias program, where we hope to have a candidate nominated for IND enablement this year. Lastly, ATI-2231, which is our second MK2 offering, is initially being developed for oncologic indications in collaboration with Washington University in St. Louis. Louis, with whom we're very tight. Okay, the next set of cassettes are basically a little bit of a deep dive on 450, 1777, and 2138. Why go after MK2? In the early 1990s, there was an awful lot of interest in activating the P38 pathway. It was thought to be kind of a master regulator of autoimmunity and immunoinflammatory diseases. Lots of companies invested in trying to drug that target, it was actually relatively easy to do so. What they all found relatively rapidly were two things. One of them is that although they saw good benefit initially in terms of biomarkers of reduced disease activity as well as clinical effect, those good effects tended to wane over the course of the next four to eight weeks. That is called tachyphylaxis. It's, I think, biologically understood how that happens, but also P38 being ubiquitously expressed and phosphorylating over 60 substrates, there was an awful lot of on-target toxicity that was undesirable, most importantly, dermatologic GI and hepatic toxicity. Interest in P38 kind of went away later in that decade until it was discovered that the virtuous sub-pathway of P38 is MK2. Again, interest in MK2, the trouble there is that unlike P38 was very difficult to drug. Joe and his very clever former Pfizer scientists at Confluence in St. Louis found a very clever way to block the activation of MK2 by creating a molecule that basically works as chemical glue between the P38 and MK2 complex, thus locking in MK2 in a catalytically inactive state, and thus preventing any of its downstream activity. To our knowledge, we're the only company that is doing it this way. There is at least one other MK2 that is out there that is actually a covalent binder at the active site. Our approach is extremely unique. What do we hope to achieve with blocking MK2? MK2 modulates the activity of multiple different cytokines, TNF-alpha, IL-17, IL alpha and beta, IL-6, and IL-8. We know from monoclonal antibodies that have come to market that knocking down any 1 of those pathways can have major effects on various diseases. The overlapping Venn diagrams you see on the left is basically just a display of what are the indications for which monoclonals are currently indicated, monoclonals against TNF, IL-17, IL-1, and IL-6. You can see the universe of indications that would be that would be privy to a molecule that could actually knock them all down simultaneously. That is the central value premise for our MK2 inhibitor for ATI-450, is that it is almost like a combination product of IL-17, IL TNF, IL-1, and IL-6 blockers. A little bit of a complicated slide, but these are the data that shows why we believe that we actually can knock all of these cytokines down. On the left are data from a healthy volunteer study. These are in vivo data. On the right is an ex vivo study of healthy volunteer donor blood. As you can see with each of these, we're seeing very appreciable knockdowns. Let's focus a little bit on the upper left-hand part of the graph, and that's of the slide rather, and that's TNF levels. At the 50 mg BID dose, which is the anchor dose for our phase II-A program and the high dose in our phase II-B portion of the program, what we're seeing is 93% knockdown in TNF presence at peak and 85% at trough. When you take into account that it also affects downstream signaling, we believe that this oral MK2 actually is eliciting TNF knockdown akin to what you see with injectable biological monoclonals against that target. You can see that similar trends are seen with basically all of the other cytokines that I mentioned. How does this translate to the clinic? Last, I guess, a year and a half ago or two years ago, we first reported on the phase II-A data of a relatively small study in patients with rheumatoid arthritis. In fact, those data were just published last week in the ACR Open Rheumatology. The citation for that is seen on the lower left-hand side of this slide. What we saw was exactly what we hoped to see, which was significant improvements in terms of quantitative markers, objective markers such as CRP, but also on clinically significant markers like ACR 20, 50, and 70. Critical in this slide is the fact that the results that we see both in terms of circulating biomarkers like CRP as well as clinical activity, is that you do not see that tachyphylaxis. Post week four, post week eight, post week 12. In fact, if anything, you're seeing a deepening of the effect as opposed to the waning that was seen with P38 inhibitors. We feel that with these data, we've kind of put to rest any concerns that MK2 might have had the same problems that P38 had. Where are we going next? I mentioned we have three different phase II studies that are actively enrolling. Let's go at these in sequence. The first that's gonna read out is our study in HS. This is a 12-week phase II-A study. It's 50 mg BID compared to placebo. These are in patients with moderate to severe HS, and we expect to see the top-line data in March or April of this year. The dosing was completed in December. We're in the post-dosing safety monitoring phase, whether it's gonna be March or April just depends on when that last patient comes in for their last sampling. Next to readout will be a large phase II-B study in rheumatoid arthritis. This is basically aping what we had done in phase II-A, including overlap of sites as much as possible. 240 subjects divided between three arms. Placebo, 20 mg BID, 50 mg BID. The patients, again, moderate to severe RA on who are not fully suppressed with methotrexate, and those data are expected in the second half of this year. At the tail end of the year, we have a phase II-A study in psoriatic arthritis. 70 patients, two arms, placebo versus 50 mg BID. These, again, are in patients with moderate to severe disease. Next, let's talk about ATI-1777, our soft JAK. We're going after atopic dermatitis, so you may all know it's an extremely attractive market. Huge prevalence in the U.S. and the Western world. A disease that does impact disproportionately young people, unfortunately people live with this disease for a very long time. The good news is that with monoclonal antibodies and with JAK inhibitors, we've seen some pretty impressive results. The trouble is, though, that with the existing standard of care, for instance, biologicals, they have a very slow onset of action in a disease that's characterized by flares, oftentimes in children. Because of the long systemic half-life after continuation of dose, if you have an adverse event such as an opportunistic infection, it could take quite a while before that's gonna resolve. As for the JAKs, again, very good efficacy. Orally administered, which is highly desirable. As you know, all of the JAK inhibitors currently indicated for RA come with a pretty onerous black box, which is a burden on patients and on physicians. The goal of the ATI-1777 program was to design from scratch a molecule that would have all of the activity of a topical JAK with minimal to any systemic exposure thus obviating the need for the labeling that is seen, for instance, with topical RUX. The good news is that, again, Joe and his folks were able to do exactly that. We reported the phase II-A data previously. There's nothing due in this slide, but just to reiterate that for the primary efficacy endpoint as well as all pertinent secondary endpoints, we saw those exactly the results that we were hoping to see. Thus prompting us to wanna get into phase II-B. Perhaps most importantly for this program, when you looked at extensive PK sampling of all 25 patients who received the drug, only three of the 25 had any detectable levels of ATI-1777 in the bloodstream. Of those three, none of them actually had drug present at every sampling. None of them had any single sample that was above the 50% of the IC50 for all pertinent JAKs. In all patients, including those three, the average presence of drug was less than 5% of the IC50 for JAK. Lastly, the systemic half-life of ATI-1777 was less than 30 minutes, and this is compared to a systemic half-life of greater than 100 hours for topical RUX. The data remains to be seen for our phase II-B study and beyond, but we actually do think that we have truly designed a soft JAK that gets all the benefits of topicals of a topical JAK without any of the downstream risk of toxicity. Where are we with it? As I just mentioned, I think that we have positive proof of concept for moderate to severe atopic dermatitis. We've been able to show minimal to zero systemic exposure, which should portend to very good labeling. The PK supports our thesis in that respect. We think this drug could be positioned either to be used in monotherapy or we think more valuably yet would be in combination with systemic biologicals. We did strike a licensing deal with a company in China called Pediatrix for development and commercialization rights for ATI-1777 in Greater China. As I mentioned before, we're expecting the phase II-B top-line data to be shared by press release and investor call in the middle of the year. The last of our clinical-stage assets is ATI-2138. We thought, given our prowess in terms of exploring the kinome, that maybe we could crack the ITK nut. There are others who've gone after this. There are offerings that are currently being developed that are ITK/JAK3 inhibitors that are heavy on the JAK3 and are light on the ITK. We designed our drug from scratch to do the opposite. It has very strong activity against ITK, with a 10-20-fold lesser activity against JAK3 and basically no activity against JAK2, which is the main driver of hematopoietic toxicity with the JAKs. You know, with that, we feel we've got a drug that could be extremely useful in terms of T-cell driven diseases. ITK, as you know, blocks T-cell signaling. The JAK3 is gonna reduce all of the IL-2 gamma common cytokines that are also pertinent in terms of T-cell activity. This is a very T-cell specific approach and could actually work in the universe of T-cell driven diseases, which I'll mention in a few slides. We just presented last fall, the SAD data we did. The beauty of having very experienced scientists like the ones we have in Joe's organization in St. Louis is that, you know, we do things very well. We did, of course, all of the usual PK and safety monitoring. No new, you know, no safety signals were detected in the single ascending dose in healthy volunteer study. The PK was as planned. It was predictable and dose-dependent. Best of all, we did do extensive PK, and we saw exactly the impact on downstream function that we expected to see. We only have one data display here, but this is basically showing a combination, a functional assay of both ITK and JAK3 function, as measured by CD3 and IL-15 induced Interferon-gamma protein production. Basically, we know that we're seeing activity both against the ITK as well as the JAK3 downstream function. This is exciting on multiple different levels, but as you may know, there are a lot of diseases that are T-cell-driven. We've decided for mechanistic and market reasons to primarily go after ulcerative colitis as our initial indication. We are planning on expanding this very rapidly. T-cell-driven diseases include all of the inflammatory bowel diseases, but also includes a lot of rheumatological diseases, RA, and others, but can even include diseases such as COPD, most importantly, asthma. There's an awful lot that we could do with this. The MAD study, as I mentioned, was started this week. It should be read out in the middle part of this year. Just to end, I did already talk to you about our people, our platform, and our pipeline. Just to add, we have robust global IP protection. For ATI-450, our composition of matter patent takes us out to 2034. With patent term extensions, we expect that to be carried out to 2038-2039. With various sundry other extensions, we should be getting out to the early 2040s. We're in a great cash position. We ended the third quarter with about $250 million in the bank, that's not including a $5 million upfront payment from Pediatrix for ATI-1777 in Greater China. Our North Star in everything we do, of course, is our patients, everything we do is urgently trying to bring medicines to squelch serious unmet medical need. We have 100 or so employees that are led by this extremely capable team. I've already mentioned Gail and Joe, who are up here at the podium with me. Also, we promoted internally our new General Counsel, Matt Rothman, as well as our CFO, Kevin, who's here. Lastly, not in the room, is Jim Loerop, our new CBO, who joined almost exactly a year ago today. Jim and Kevin are gonna be very active this coming year because we have a lot going on. This is basically a redux of the pipeline slide that you had seen earlier, but just mentioning where we're at currently with partnerships. We have the one deal for Greater China for ATI-1777, but we are looking for partners for all of our assets. We believe that ATI-450 has the potential to be a mega blockbuster oral INI drug. To realize its full revenue potential, we probably, with a partner, will need to begin phase II studies in as many indications as we think are viable to accelerate the time to peak sales. We're looking for partners for 450 as well as for the rest of the world for 1777 and even for 2138. If you wanna leave this talk with any punchline, it is this. This is gonna be a great year in terms of clinical data readouts for us. Five major readouts across three programs. Just to go through this sequentially again, ATI-450 phase II-A in HS is gonna read out in March or April of this year. ATI-1777 atopic dermatitis phase II-B is gonna read out in the middle of the year. ATI-450 study in RA, the phase II-B, the 240 patient study will read out in the second half, as will the MAD study for ATI-2138. Closing it out will be our ATI-450 PSA phase II-A at the end of the year. We're looking forward to an exciting year, and my team and I are more than happy to answer any questions you may have. Thank you. Please also feel free to submit questions online if you prefer that. Doug, why don't we start off with a few questions from me? Sure. Thank you. Can you please help us think about what you're looking for with the HS trial data? Let me start, and then I'm gonna have both Joe and Gail speak to this. The decision to go into HS was made before I joined the company, but I think it was an extremely wise one. Psoriatic arthritis and RA tend to kind of co-migrate together in terms of activity. We see the PSA phase II-A study as being much more confirmatory. The read-through study for our phase II-B in RA was the successful phase II-A in RA. That we think is kind of taken care of. HS is kind of at the opposite extreme of the spectrum in terms of diseases to address with a drug like this. If we see a good signal there, I think that we and others are gonna think that we truly are an oral version of TNF plus, TNF plus IL-17, TNF plus IL-6. Mechanistically, we think that it's an obvious place for us to be going. If you look at successful drugs in the HS space, obviously HUMIRA is the only one approved currently in the U.S. But there's a couple of phase III studies for IL-17 that just came out that, you know, are consistent with our thesis that in fact knocking IL-17 down also could help. And even the IRAK4 data would suggest that that's very much aligned with our kind of central thesis mechanistically. I'll get Joe first to kinda elaborate on why we think this is gonna work, and I'll get Gail then talk about the. what we expect to see in this study. Yeah. As Doug said, mechanistically, the MK2 pathway regulates the production of these key cytokines that are involved in HS, such as IL-17, both A and F, as well as TNF-alpha, IL-8 and IL-1 alpha and beta. In addition, it regulates the signaling of a subset of these cytokines, namely IL-1 alpha and beta, TNF, as well as IL-17. Understanding the biological data from the compounds that are now in late clinical development or on the market and the mechanism of those, it matches up perfectly with ATI-450 and in inhibition of MK2. Yeah. In terms of the study, I think, from a phase II-A study, this is our first chance to see how well this mechanism will play out in a disease like HS that really represents still a large unmet medical need. Our primary endpoint is change in nodule count. I think what we'd most like to see is that our results on the primary endpoint, on key secondaries are well within the ballparks that we've seen from the TNF inhibitors and from IL-17 inhibitors, and that our safety profile is promising. It's a phase II-A study, so every piece of data will be important from PK to PD to primaries to secondaries in helping us understand how this drug works here and where to go next. Just as a follow-up, can you talk about what does a bar or what does good look like for this data? I think, let's go back to that ballpark that the TNF inhibitors are in, the IL-17 inhibitors are in. I think, what you saw in the PIONEER studies with HUMIRA was a change in nodule count of three to four. You know, I would hope we're at least in that ballpark. I think based on the mechanism and the fact that we, as Joe said, and as Doug said, not only do we hit TNF, not only do we hit IL-17, but we hit cytokines that impact neutrophil activation, neutrophil effects, which is a very important part of this particular disease. You know, I think more would be better, but I would be pleased to get us in that ballpark of three to four. Amazing. Thank you all. If the audience doesn't have more questions, I'll continue with more questions from me. Should we think about the results of the HS trial having any read-throughs to the RA and the psoriatic arthritis trials? As I mentioned, I don't think there's any efficacy read-through, positive or negative in that respect. Again, the predicate for phase II-B success in RA was the phase II-A. I do think the read-through is gonna be on safety. Just to give people an appreciation of the size of our safety database, we currently only have 15 patients that have been exposed for any period of time that have been unblinded, and those are the patients that were in the RA phase II-A study. We'll be adding another 45-50 patients with the HS data readout in March or April of this year. There'll be another 160 patients with the RA phase II-B readout, and another 35 patients in the psoriatic arthritis phase II-A readout. By the end of this year, we'll go from having safety data on 15 patients to 250 patients. We think that that is gonna. Obviously, we'll ultimately need to have a larger safety database to get the drug approved in the U.S. and elsewhere, but we think that that's gonna be a large enough, a critical mass of safety data for us to have a pretty good idea on what the profile is. I will say to you, though, pre-clinically, we have not seen any signature toxicities with this drug and thus with this drug class. We've already mentioned that clinically, we haven't seen anything akin to P38. In fact, we haven't really seen anything at all. Pre-clinically, we have completed four 12-week studies, as well as six and nine nine-month studies. We're waiting to get the final histo readout on the chronic pre-clinical tox. In every study to date, we have not hit an effect level. The highest dose exposed was, in fact, the no effect level. All of this augurs well. You know, you don't declare victory until you see the data, but we think it's, the drug is actually looking pretty good, and we are very confident that we don't have any of the liabilities of the P38. Amazing. Amazing. I know we've talked a lot about ATI-450, but one more question on competition in the MK2 space. Can you share your thoughts about Bristol's MK2 inhibitor and how it is different than ATI-450? I'm gonna ask Joe to answer that, please. The only two compounds that are in clinical development that target MK2 are ATI-450 and the Bristol compound CC-99677. Mechanistically, they're distinct. Our compound, as Doug said, targets the P30 MK2 complex selectively and locks MK2 into an inactive confirmation. The Bristol compound is a covalent inhibitor of MK2, taking advantage of the cysteine residue at the active site. Mechanistically, they're distinct. When you look at the potency, and BMS has published a couple of manuscripts last summer that described their pre-clinical and early clinical work with their compound. Potency-wise, looking at cytokine regulation, ATI-450 is 10-30 times more potent in cellular assays than is the BMS compound. When you look at kinome selectivity, ATI-450 is very selective against the human kinome. One of the more selective inhibitors that have been published on. The BMS compound has about 9 kinases that it hits harder than it hits MK2. Some of these kinases, it hits reversibly, so you gotta take that into account when you look at the selectivity profile. Thirdly, looking at the doses that are being used in clinical studies. As Doug said, we're looking at 50 mg, our anchor dose for ATI-450 in our phase II studies. With that dose, we're knocking down, for example, TNF-alpha levels somewhere between 85% and 93%. The BMS compound at their highest dose in their ankylosing spondylitis phase II study, which is the single phase II study that they're looking at their compound in. At that high 150 mg dose, they're modulating TNF maximally at 70%. We're able to, with ATI-450, interrogate a broader range of pharmacodynamic modulation, and try to correlate that disease efficacy. That's sort of a comparison, both from functionally and structurally between the two compounds. Thanks, Joe. Thank you, Joe, for your very comprehensive response. Next, I would like to touch on our JAK inhibitors. Can you please describe the mechanism of ATI-1777 and what is meant by soft? Again, Joe, I'll tap you for this. Okay. 1777 is a compound that we specifically designed to be a topical JAK inhibitor. Instead of taking an oral JAK inhibitor and just repurposing it for topical administration, we purposely built in physical chemical characteristics into ATI-1777, a selectivity profile that we were interested in. 1777 selectively inhibits JAK1 and JAK3, which we think is, are the critical JAK isoforms for efficacy in atopic dermatitis. It was built as a soft compound, which means that it's active in the skin, but once it gets into the systemic circulation, it rapidly degrades. We purposely built in four metabolic soft spots into the molecule, such that when it does get through the skin and to the circulation and through the liver, it doesn't stay around at all. With this compound, we believe this could be best in class and that it should have the efficacy of the topical RUX, for example, or the oral JAK inhibitors, but it should have a dramatically improved safety profile. That, and as Doug showed, systemically, we're not seeing any compound present. That's sort of the, how we designed it. The data that came out in the phase II-A study in atopic dermatitis just bore out the that we were accurate in how we designed the molecule. I would just add from a marketing perspective, so Incyte's doing the heavy lifting in terms of creating that market, but I think everyone has been pleasantly surprised at how well the launch has been going. That augurs well for us. I think that, you know, clearly the negative black box label, the warnings in the label are a major break in terms of uptake, and we think that we'll be able to overcome that. Yeah. Now I would like to turn to ATI-2138. Can you please discuss a little bit of the rationale behind choosing UC as the first disease target? Yeah. Let me start, and maybe Gail, who actually led the effort can add her color commentary. As I mentioned, we knew that we had the universe of T-cell driven diseases available to us. The filter that we used, we just wanted to take a mechanism that was well understood, where there has been precedent in terms of smallish phase II POC studies that could kind of de-risk on efficacy, and a pathway where, you know, there was known regulatory imperatives, and where there was an attractive market. We could have gone in other directions, and we actually you know, went through 18 different diseases to land on UC, but I think it is the right initial vehicle. I think the question for ATI-2138 is how broad do we go, how quickly in terms of other T-cell driven diseases. Gail, anything you wanna add? I'd only add briefly that I think ulcerative colitis is still a disease with a really a need for other treatments. Cyclosporine is a kind of a good example of a T-cell inhibitor, but one that has too much toxicity and particularly for a disease like ulcerative colitis. The hope is 2138 has that sort of efficacy, but with a much improved safety profile. It, it, you know, given the unmet need there, that seemed like the lead place to go, and there was great preclinical data specific to 2138, excuse me, and inflammatory bowel diseases that told us that this is a good first start. Where we go after that is really very, very broad and very open. Yeah. Just to add, I think an external validation of this thinking was the Pfizer acquisition of Arena. That was to, you know, get their lead asset, etrasimod. It's an S1P inhibitor that basically blocks T-cell trafficking. It's a pure T-cell play. It was validated in phase III for UC, we're kind of following on the footsteps there. Amazing. Amazing. Thank you so much for all your responses. I would lastly like to congratulate you, first of all, on all the successes, and progresses made last year. Could you please comment on all the recent leadership changes that were announced late last year? Sure. I, as I mentioned, I joined the company in August. My joining was part of a strategy by Neal and the board for succession planning and as well as for capability enhancements. As I mentioned last year, we hired Jim Loerop in January to be our CBO. Gail joined in June. I joined in August. Our new head of IR, Bob Doody, who's in the front row, joined in September. We wanted to kinda bolster our overall capabilities, most importantly in development, which I thought we did so. Both Neal and Frank Ruffo, the former CFO, were both contemplating retiring well before the start of the year, but to do so, you really need to do good succession planning. What you want to achieve when you're especially changing CEOs, is you want the announcement to be greeted by a collective yawn, you know, by the investor community. I think that we did exactly that. Didn't know when the transition was gonna occur. Thought it probably would occur. The board and Neal felt comfortable with announcing it in November and making it effective on January 1st. I think my likelihood of success is enhanced by the fact I have this incredibly strong team, and I mentioned Kevin and Matt as recent additions to the C-suite. I think we've got exactly the right senior personnel to be able to realize the value of this company in the next, you know, year and years to come. We have a question coming through, the iPad. The question comes from Swapnil Tejwani, Dr. Warley Capital. The question reads, "Looking at the recently published phase II-A data in RA, can you please comment on the relatively milder disease severity of those patients relative to other RA trials run in approved agents? Well, I'll let Gail give the bulk of this answer, but just to recapitulate. The phase II-A study was actually executed, I think, a total of 17 patients, 15 on active drug to two placebo. These were patients with moderate to severe disease. There was no cap in terms of prior biologic and JAK exposures. In fact, all of the patients were enrolled in the U.S. and not surprisingly, based on standard care practice here, more than half of them actually did have biologic or JAK experience. I take a little bit of an issue in terms of the comment that they were less severe disease, but I'll let Gail elaborate. Yeah, I mean, I think there's other ways to look at severity, disease activity, CRP scores, joint counts. You know, we aimed to enroll a population that would show efficacy and would allow us to progress the drug, and I think we saw excellent efficacy. I think our current study has a fairly similar study design to cap the biologic and JAK experience patients, with still an emphasis on the need for very active disease. Just to add, I'm just bringing back the slide. These are the results that you'd expect to see in naive patients, right? Yes, it's a small sample size and one could quibble about the veracity of the point estimate, but what we wanted to see here was basically a significant reduction in DAS28-CRP, akin to what you see with JAKs and biologicals. Box checked. What you wanna see is the relative success that one needs to see in terms of ACR 20, 50, and 70. It's 60, 40, 20, kind of is what you're hoping to see, and that is exactly what we found. Again, I reiterate, this is in a population where half of them had already failed TNF and/or JAKs. With that, we're coming up on time. Thank you everyone for coming, and, thank you, Doug, Joe, and Gail.