Good morning, ladies and gentlemen, and welcome to the Aclaris Therapeutics Corporate Update Conference Call. My name is Kate, and I will be your conference operator today. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. If you require any assistance during the call, please dial star then zero on your touch-tone telephone. As a reminder, this conference is being recorded. I would now like to turn the call over to Matthew Rossman. You may begin. Thank you. I am Matthew Rossman, Chief Legal Officer and Corporate Secretary for Aclaris. Please note that earlier today we issued a press release relating to an exclusive license agreement and other corporate matters. For those of you who have not seen it, you will find the release posted under the press releases page of the investors' section of our website at www.aclaristx.com. In addition, we'll be referring to a slide deck entitled Corporate Overview, which can be found on the events page of the investors' section of our website and attached as an exhibit to our Form 8-K that we filed with the SEC earlier today. Joining me for the call are Neal Walker, our Interim Chief Executive Officer, Hugh Davis, who we're pleased to welcome as our new President and Chief Operating Officer, Joe Monahan, our Chief Scientific Officer, and Kevin Balthaser, our Chief Financial Officer. Before we begin our prepared remarks, I would like to remind you that the various statements we make during this call about the potential benefits of the in-licensed assets, the company's future results of operations and financial position, business strategy and plans, and objectives for Aclaris' future operations are considered forward-looking statements within the meaning of the federal securities laws. Our forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions, and uncertainties that could cause actual results to differ materially from those reflected in such statements. These risks are described in the risk factors section of Aclaris' Form 10-K for the year ended December 31, 2023, and other filings Aclaris makes with the SEC from time to time. These documents are available under the SEC filings page of the investors' section of our website at www.aclaristx.com. All information we provide on this call is provided as of today, and we undertake no obligation to update any forward-looking statements we make on this call on account of new information, future events, or otherwise. Please be advised that today's call is being recorded in webcast. A link to the webcast can be accessed under the events page of the investors' section of our website. I'll now turn the call over to Neal. Thank you, Matt. Good morning, everyone. Earlier in the year, we announced that we were conducting a strategic review of our business. This was a comprehensive process that involved the assessment of numerous opportunities over the last several months. In parallel, we have generated non-dilutive capital through the monetization of a royalty stream involving one portion of our JAK inhibitor IP estate. We also developed a go-forward strategy for our internal assets while maintaining a lean cost structure. As of the end of the third quarter, the results of these efforts have generated a cash, cash equivalents, and marketable securities balance of $173 million, nearly what we started the year with, and a new internal plan to continue to generate important data readouts in the coming years. Today, I am pleased to announce the conclusion of our strategic review, an exclusive license deal with Biogen for two biologics, the addition of two key executives to our team from Biogen, and an $80 million financing led by Vivo Capital along with a top-tier syndicate. Turning to slide three in the corporate deck, with the Biogen transaction, we are adding two biologics, a phase II TSLP monoclonal antibody with best-in-class potential and a near-to-clinic bispecific TSLP IL-4 antibody with similar best-in-class potential. With these two portfolio additions, we now have four programs across both large and small molecule therapeutics. As a reminder, ATI-2138 is an oral small molecule covalent inhibitor of ITK JAK3. We are currently conducting a phase II proof-of-concept study in moderate to severe atopic dermatitis. In addition, we have a next-gen ITK oral small molecule program that is in preclinical studies with an IND anticipated in the first half of 2026. This transaction transforms us into a clinical-stage company with dual large and small molecule expertise. It also effectively overdoubles our potential catalysts within our cash runway, which, when combined with our existing capital and the capital from the private placement that we also announced this morning, we maintain is into 2028. Following the upfront payments to Biogen and our expected net proceeds from the private placement financing, our new pro forma cash, cash equivalents, and marketable securities position based on our balance sheet as of September 30, 2024, is $213 million. Turning to slide four, we now have four assets as shown on the left along with our proprietary small molecule discovery engine. In addition, we enhanced our management team and have world-class small and large molecule expertise. Slide five. Here's the team. We have added Hugh Davis with over 35 years of experience in biologics. We also added Steve Knapp with over 35 years of experience in the space. Both joined us from Biogen. Turning to slide six. The new pipeline now includes BSI-045B in phase II and BSI-502, which is the bispecific, currently, and IND-enabling tox work. I will now hand it over to Hugh Davis, President and COO, to review the newly added Biogen biologic opportunities. Hugh? Thanks, Neal. Good morning, everyone. On slide eight, I'd like to jump in on TSLP and give an overview of the Th2 pathway and the involvement of TSLP in driving immune activation in barrier surfaces such as the skin, lung, and GI tract. Activation of TSLP drives T-cell activation in factors such as IL-4, 5, and 13, our key modulators of that effect. The activation also induces chemokines such as CCL17 that ultimately drives immune cell recruitment and pathogenesis. Tezepelumab has been approved for the treatment of severe asthma by inhibiting TSLP and this downstream process. Although Tezi narrowly missed on their primary endpoint in AD, it did demonstrate some success in a phase IIa study where it showed clinically significant reductions in IGA 0 and 1 versus placebo at 16 weeks. The phase IIb did not reach targeted levels of efficacy, however. It's our opinion that a higher potency antibody therapeutic would show clinically significant impact in AD. BSI-045B shows much higher potency, lower dissociation, and longer residence time on TSLP than Tezepelumab. On slide nine, BSI-045B shows about 60-fold higher potency than Tezepelumab in inhibiting CCL-17 release from TSLP-activated PBMCs. This is thought to be a function of the very low dissociation from TSLP and longer residence time on TSLP. BSI-045B exhibited a half-life of about 23 days in healthy volunteers and AD participants in clinical trials. On slide 10, the long residence time is shown for BSI-045B and BSI-502 relative to other anti-TSLP mAbs in clinical development. BSI-045B and 502 both show residence times on TSLP of greater than 400 hours, while the other anti-TSLP mAbs are only about 5 to 20 hours. On slide 11, the previous finding data is translated into functional effect with an assay that shows that BSI-045B and BSI-502 has the most potent inhibition of CCL17 by TSLP-activated PBMCs of the assets that we evaluated. As you can see in the table on the right, all the other anti-TSLP and TSLP receptor mAbs have IC50 values between 2- and 70-fold higher than BSI-045B. On slide 12, BSI-045B was evaluated in a phase IIA clinical trial in participants with moderate to severe AD. Twenty-two subjects with moderate to severe AD with a mean EASI score of 17.6 and a PP-NRS of 6.5 were enrolled at seven U.S. sites. The study had four weekly induction doses of 300 milligrams, followed by doses every other week through 24 weeks, followed by a 12-week follow-up period without further addition of drug. This would allow for an assessment of PK/PD to identify useful dose regimens for phase IIB. On slide 13, the PK and PD of the drug is shown. In blue, it's shown that the concentration of drug over time reaches steady state by the fourth dose and remains steady throughout the maintenance period. Following the last dose at week 24, the concentration begins to wane. This reduction in concentration occurs slowly over time, which is indicative of a long half-life monoclonal antibody. The green line shows the change from baseline of EASI score over time. By four weeks, the study participants exhibited a 50% reduction in the percent change from baseline. The response of BSI-045B continues to climb through the maintenance period. The maximum effect isn't realized until four weeks after the last dose. This supports the possibility that the drug could be administered on a longer dosing interval. As shown, the drug maintained at least a 75% change from baseline even at 12 weeks post the last dose. On slide 14, the clinical effect is shown quantitatively with 94% of the 17 study participants who completed the study achieving a 75% EASI reduction. About two-thirds exhibited a 90% EASI response, and a quarter of the participants achieved complete response with an EASI 100, and 88% of participants achieved an IGA of 0 or 1, clear or mostly clear. On slide 15, the safety profile of BSI-045B shows that the monoclonal antibody was well tolerated and exhibited a similar safety profile as other anti-TSLP mAbs. Injection site reactions were all grade 1 and didn't require pre-medication or medication post-dose. Follow-up injections did not show a worsening of the ISR. The antidrug antibody incidence was one out of 21 participants, and that titer was low. ADA did not show a clinically significant impact on the observed PK exposure. On slide 16, BSI-045B is plotted alongside the phase IIa Tezepelumab plus TCS versus placebo data, the SOLO I and II dupilumab phase II monotherapy data, and the phase III dupilumab topical corticosteroid combination data. As you can see in this plot, dupilumab monotherapy responses in SOLO I and II flatten out at about 60%-65% of EASI response. The Kronos study, dupi plus TCS, flattens out at a slightly better response at 75%. Dupilumab showed 68% of their subjects achieved a 75% EASI response relative to 22% of placebo achieving the same endpoint. In the phase IIa trial of BSI-045B, 94% of participants exhibited an EASI-75 response. On slide 17, a comparative summary of BSI-045B relative to other approved biologics in AD, namely dupi, Trelo, and lebrikizumab, in addition to an oral JAK such as upadacitinib, shows that BSI-045B participants exhibit substantially greater EASI response in the phase IIA trial than these approved agents in their trials. 94% of BSI-045B participants exhibited an EASI-75, while the other approved biologics show between 56% and 70% EASI-75 response. BSI-045B shows that 65% of subjects achieved an EASI-90 response, while the approved biologics exhibited 33%-41% EASI-90. And BSI-045B drove 88% of IGA 0/1 responses, while the approved biologics exhibited between 39% and 41%. And those clinical trial results are for BSI-045B as monotherapy versus dupi, Trelo, and lebrikizumab being in combination with topical corticosteroids. The phase IIA study was, however, open label and not placebo-controlled, along with a small sample size. Nevertheless, it's clear that BSI-045B exhibited clinical activity that is differentiating from approved therapies. On slide 18, the properties of BSI-045B are summarized. BSI-045B exhibits very high affinity due to its extremely low dissociation from TSLP and a very long residence time, over 20- to 100-fold longer than any other anti-TSLP mAbs that we evaluated. This potency has translated into very high clinical response in moderate-to-severe AD. Together with the phase II data to be delivered from our China partner, CTTQ, we believe BSI-045B is one of the most advanced anti-TSLP mAbs in clinical development. The phase IIa data suggests that BSI-045B could be a best-in-class therapy in severe asthma and chronic rhinosinusitis, as well as a first-in-class asset in atopic dermatitis. On slide 19, in addition to Aclaris licensing an anti-TSLP mAb, Aclaris also licensed an anti-TSLP IL4R bispecific mAb from Biogen. Moving to slide 40, BSI-502 is a bispecific monoclonal antibody that exhibits the same high binding, very low dissociation from TSLP, and very long residence time on TSLP as BSI-045B. In addition, BSI-502 has been Fc engineered with a YTE mutation to enhance FCRN binding that will extend its half-life and an AQQ mutation to eliminate its effector functionality, thereby minimizing any anti-Fc gamma receptor off-target cellular toxicity. On slide 21, in the same functional assay previously described for BSI-045B, PBMCs were activated this time with both IL-4 and TSLP. In slide 22, it's shown that Dupixent is able to lower the AER by 29%-34% relative to placebo, and for this, Dupixent has been approved for the treatment of patients with COPD. Tezepelumab has shown a similar decrease in the AER in COPD patients in their course study. It seems reasonable that an agent that binds and inhibits TSLP and IL4R with greater potency than Tezspire or Dupixent should show greater impact in this disease indication. BSI-502 is well-suited to be investigated in this indication as well as other respiratory and dermatologic diseases. Slide 23 provides the summary of BSI-045B and BSI-502. BSI-045B is the leading anti-TSLP mAb program in both severe asthma and atopic dermatitis. BSI-045B has demonstrated functional superiority to market leader Tezspire in affinity, potency, and neutralization potential. Phase IIa data in a single-arm study in AD show that over 90% of subjects achieved an EASI 75% reduction in their disease. BSI-045B has first-in-class potential in AD and best-in-class potential in severe asthma. BSI-502, a bispecific mAb to both TSLP and IL-4R, has exhibited superior potency relative to the combination of Tezi and dupi combined in an ex vivo study of CCL17 release inhibition from IL-4 and TSLP-activated PBMCs. BSI-502 also has best-in-class potential across many disease indications, including severe asthma, atopic derm, and COPD. BSI-045B and BSI-502 combined represent an immunology franchise portfolio. I'll now turn the call over to Joe Monahan, our senior chief scientific officer, who will now discuss our ITK portfolio. Thanks, Hugh. We'll now switch gears to describe our program focused on the oral small molecule kinase inhibitor ATI-2138. As shown on slide 25, ATI-2138 is a covalent inhibitor that targets two key kinases involved in the inflammatory process, ITK and JAK3. ITK is downstream of the T-cell receptor, and inhibition of this signal transduction enzyme blocks T-cell differentiation and activation, with a particular emphasis on Th2 cells. Inhibition of JAK3 disrupts signaling of the gamma common cytokines that regulate T-cell biology, such as IL2, IL4, and IL7. ATI-2138 is highly specific for the JAK3 isoform, exhibiting several thousand-fold selectivity over the other three JAK kinases. Additionally, both JAK3 and ITK expression is limited to hematopoietic cells in contrast to other TEK and JAK kinases that are ubiquitously expressed, thereby decreasing the probability of inhibitor impact on other organ systems. SAD and MAD work have been completed with ATI-2138, and we are currently enrolling in a phase IIA atopic dermatitis study. ATI-2138 can be considered a fast follower to ritlecitinib, a covalent JAK3 inhibitor that has some crossover on TEK kinases. Ritlecitinib has been approved for alopecia areata and is in late-stage clinical trials for vitiligo, Crohn's disease, and ulcerative colitis. A comparison of the cellular potencies of ATI-2138 and ritlecitinib is described on slide 26. Evaluation of ATI-2138 and ritlecitinib in human whole blood studies demonstrates a potency differential. ATI-2138 is 40-50 times more potent in blocking ITK-dependent interferon gamma production and five times more potent in inhibiting IL2-induced JAK3-dependent cytokine production. Furthermore, ATI-2138, in contrast to ritlecitinib, demonstrates similar potency at blocking both ITK and JAK3, consistent with the dual pharmacology expected at a given dose and exposure. Another relevant molecule is the ITK-selective clinical stage inhibitor CPI-818, or soquelitinib, currently in clinical trials for T-cell lymphoma, other cancers, and atopic dermatitis. CPI-818 is selective for ITK over JAK3 and other TEK kinases, and we have evaluated it in comparison to ATI-2138, as shown on slide 27. Enzyme inhibition studies comparing CPI-818 to ATI-2138, specifically with respect to ITK potency, is shown on the left-hand table and demonstrates that ATI-2138 is 15-38 times more potent than CPI-818 for inhibiting the ITK enzyme activity. As ITK is critical for the differentiation and activation of Th2 cells, we carried out studies examining the impact of these compounds on the activation of Th2 cells differentiated from human CD4-positive cells by examining Th2-specific cytokines IL4, IL5, and IL13. These data show that ATI-2138 has an IC50 for inhibition of these three cytokines of about 10 nanomolar, and complete inhibition is observed at 100 nanomolar. With CPI-818, no inhibition is observed but below 3 micromolar, resulting in approximately a 100-fold potency advantage for ATI-2138. These data support the best-in-class potency potential for ATI-2138. Three clinical studies supported advancing ATI-2138 into clinical development. As shown on slide 28, ATI-2138 completed SAD and MAD studies and demonstrated a well-behaved PK profile across the dosing range between 5 mg and 40 mg b.i.d. Steady-state exposure was dose-proportional for both Cmax and AUC, and the compound was generally well tolerated and demonstrated an acceptable safety profile. We also evaluated PD markers in these studies, as shown on slide 29. PD analysis of blood samples from the MAD study was carried out using ex vivo stimulation of the ITK pathway on the left, the JAK3 pathway in the center, and the simultaneous stimulation of both pathways on the right. Time and dose-dependent inhibition was observed with ATI-2138 across a significant portion of the dosing interval with each dose. Phase I data supported moving into phase II. Atopic dermatitis was chosen as the first indication based on cost and timing efficiency, unmet need, and the strong scientific rationale for ATI-2138 in the disease, as shown on slide 30. As mentioned earlier, ITK is critical for Th2 cell biology, and Th2 cells are key drivers in atopic dermatitis. Biologics that target the important Th2 cytokines IL4 and IL13 are efficacious in AD, and from the JAK3 standpoint, JAK3 regulates the signaling of key cytokines such as IL2 and IL4, and JAK inhibitors also work in AD. A drug like ATI-2138 that blocks both Th2 signaling and JAK-associated cytokine signaling has strong rationale for the treatment of atopic dermatitis. An overview of the phase II study is shown on slide 31. The phase IIA AD study is underway and is currently enrolling patients. It's a small open-label study of up to 15 moderate-to-severe AD patients to be treated for 12 weeks with a 10-milligram b.i.d. dose of ATI-2138. Readouts, in addition to safety and PK, include the typical AD efficacy endpoints, and in addition, there is a strong PD component focusing on ITK and JAK3 modulation signatures in skin and blood. In summary, as shown on slide 32, ATI-2138 is an oral compound that demonstrates dual pharmacology blocking both T-cell function with a focus on Th2 cells as well as gamma common cytokine signaling through ITK and JAK3 inhibition, respectively. The SAD and MAD studies in healthy volunteers have been completed, resulting in an understanding of PK/PD relationships and demonstrated a well-tolerated safety profile. The phase IIA study in AD is underway, and successful completion of that study will pave the way for evaluation of additional T-cell and JAK2 diseases. To complement ATI-2138, we are currently advancing a second-generation ITK inhibitor program in Aclaris discovery, as shown on slide 34. Our second-generation program will focus on the two T-cell-specific TEK kinases involved in TCR signaling, ITK and TXK. While ITK alone is sufficient for the Th2 and Th17 cell differentiation and activation, a combination of ITK and the related kinase TXK are required for Th1-driven biology. As such, the second-generation project goals are to engineer out JAK3 cross-reactivity to eliminate the potential for JAK-related black box warnings, to deliver a highly potent and selective ITK development candidate for utility in Th2-driven atopic and allergic diseases, and to deliver a second development candidate that, again, is devoid of JAK3 inhibitory activity but inhibits both ITK and TXK. This pharmacological profile will have the additional potential to impact Th1-driven diseases such as RA, MS, and Crohn's disease. We anticipate the nomination of one to two development candidates in the upcoming months to support IND filing planned in the first half of 2026. I will now turn the call back over to Neal for closing remarks. Thank you, Joe. Before we shift the call to addressing your questions, I would like to make a few final comments. Today's announcement represents the successful completion of our comprehensive strategic review process. Through the license agreement with Biogen, we have significantly enhanced our pipeline with BSI-045B, which has already demonstrated compelling phase IIA proof-of-concept data in atopic dermatitis, and BSI-502, a novel near-to-clinic bispecific antibody. These assets complement our existing ITK inhibitor portfolio and position us well across multiple high-value indications. We've also taken this opportunity to strengthen our executive team and to add to our already strong balance sheet. Combined, we believe we have the leadership, assets, and resources in place to become a leading immunology company. Operator, we would now like to open the line for questions. At this time, I would like to remind everyone, in order to ask the question, press star and then the number one on your telephone keypad. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Louise Chen with Cantor Fitzgerald. Please go ahead. Deal, and thanks for taking my questions here. So I had a few for you. I wanted to ask you, basically, first, for the BSI-045B study, how many patients were moderate versus severe, and what are the ages of those patients in your study? Thanks, Louise. Yeah, most of them were moderate. I think the average age was around in the 40s, but it extended from about 18 to 70 or so. Okay. And if they're moderate, then how do you think that gives you confidence that going into a moderate or severe population in later studies will work out for you? Yeah. So there's actually been quite a bit of work on this. Over time, as we've seen more therapeutics get into atopic dermatitis, we've seen less severe patients included just because they aren't available. And there's been a number of papers that have opined on this topic. Basically, moderate and severe patients respond the same. It really is a continuum, so it's not something we're concerned about at all, and the data was quite robust. Okay. Then why do you think your drug keeps working post your stopping the last dose versus other drugs just revert back for the BSI-045B? Thank you. Sure. Well, let me comment first, and then I'll hand it over to Hugh. I think the key is, and this is something in the slides that we took great pains to include because we did all this work. We wanted to understand and characterize this molecule versus the competitive set, and it really comes down to the long residence time. When you look at that TR-FRET data, it's quite stark that it's a very sticky molecule, and I think that's a key contributor. Do you have any other thoughts on that? Really, what you said is accurate in my mind. TSLP in the deep tissue space, especially in the skin, is at very low levels, picogram per ml quantities, and you need to be able to inhibit that locally in order to prevent any autocrine or paracrine effect. That's what 045B does, is it doesn't come off of TSLP in this deep tissue space, and then that allows the skin to heal better. Thank you. Your next question comes from the line of Thomas Smith with Leerink Partners. Please go ahead. Hey, guys. Good morning. Thanks for taking the questions, and congrats on the updates. Just I was wondering if you could comment on how competitive this process was, Neal, and then maybe just elaborate on how much diligence you were able to do on the 045B and the bispecific, both on the assets as well as the existing clinical data, just to get comfortable with these compounds. Sure. It's interesting that there's a lot of transactions out there, Tom, with China-based assets, and we were fortunate to get introduced to Biogen, and they're brilliant discovery chemists, and they've been doing this a long time. A lot of these guys have pedigrees reaching back into companies like AbbVie and other multinationals, so just phenomenal work by them and their team. Then they get to a point where you almost have to pass the baton off to do the rest of the clinical work. You can imagine there's been increasing interest in China-based assets, and so there was a lot of interest. We came into a process that was pretty much towards the end, and we were able to prevail in that, basically on the heels of having our complementary team and kind of a grander story around combining both assets. So that's kind of point one. On the diligence front, we've been working on this for about five, six months, and a key to this was doing a lot of repeat work. The Biogen team did a phenomenal job of generating a lot of great preclinical data showing how they stack up to Tezspire. We wanted to repeat all that work, and fortunately for us, we have this phenomenal resource in St. Louis where we can do all this testing in-house against various assets, including the competitive landscape. So we added, in addition to retesting, repeating all the work at Biogen and then having WuXi AppTec repeat all that work, so we did it in triplicate. We did it across both assets, and what we presented to you was just a snapshot of that. There's a lot of other data behind it, but it all represents the same trend, the same pattern. And again, I'll just point to the TR-FRET data. I mean, when you're able to quantitate that long residence time, that really is the reason to believe why you're going to get the functional inhibition that we're seeing in other assets, plus now in the clinic. Got it. That makes sense. And then with respect to the two clinical readouts coming from China in asthma and chronic rhinosinusitis, can you just elaborate a little bit on the design of those studies and what doses are being evaluated there? Is it the same dosing that was used in the phase IIa atopic derm study? And then can you also talk about your expectations for each of those readouts? Are there any specific benchmarks that you're looking for to maybe boost your confidence in the asset? Yeah. Let me start, and I'll hand to Hugh for the specifics. But that's a key point, Tom. I'm really excited that Biogen had partnered those assets in China and spending quite a bit of money on a comprehensive phase II program in respiratory diseases. For us now, to me, it's kind of a call option. We get to look at the data as that comes in in the early part of 2025. And when you think about it, we've got an AD POC, we've got two respiratory studies that are towards the end of phase II, and long studies, like 52-week studies on the severe asthma front, and that starts to come into focus in 2025. And maybe on some of the specifics, I'll hand that off to Hugh on dosing, etc. Yeah. So CTTQ is the partner in China, and the two trials for severe asthma as well as chronic rhinosinusitis with nasal polyps are in ClinicalTrials.gov, and they use a different number. It's TQC2731. But to answer your question specifically, the severe asthma trial is a 52-week design with 204 subjects, and they investigate doses of 210 mg and 420 mg at every four-week dosing. And that trial will read out toward the end of second quarter of 2025. And then the CRS with nasal polyp is a 60-patient study at the same two-dose levels for 24 weeks, and that will read out also the middle of 2025. Got it. That's helpful. All right, guys. Thanks for taking the questions. Appreciate it. Thank you, Tom. Your next question comes from the line of Chris Raymond with Piper Sandler. Please go ahead. Hey. Thanks for taking the question, and congrats on this deal. Very intriguing data. I guess maybe on BSI-045B, just curious, you measured response at 26 weeks. I think Dupixent and other AD therapies have looked at 16 weeks. Maybe just curious why that time point was chosen. And then maybe a second question. There's been some debate about TSLP in AD, and I get the comparison to Tezspire. Do you think it was really just potency that caused sort of the middling sort of data that they had there, or is there some other aspect to Tezspire that you think drove that? Thanks. Yeah. Sure. Thank you, Chris. So I think the endpoint for this first kind of what I would call the signal-generating study was it was purposeful. If you look at similar targets like OX40, they go out to 24 weeks, etc., because when you target this pathway, it takes a little bit of time. But as you can see in our data, the curves were pretty sharp even in the beginning, but you want to make sure when you're trying to figure out the signal that you take it all the way in this regard. But even at 16 weeks, the data is quite good, and I think moving forward, we'll look at perhaps an earlier time point. But I think in something where you're in a disease where you're treating the flare, and this is a big difference between AD and psoriasis, you're much better off having a smooth, deep effect that kind of persists over time rather than a choppy effect because you have that inherent in the disease. So I think that was, at least for this design, it made a lot of sense. You want to load up a drug, and then we did, or I should say Hugh and the team did every two weeks, even though we think we have PD to support longer dosing intervals because we really want to understand, is AD a viable target? As it relates to the Tezspire data, I think there's always nuances in all these studies. You can critique maybe some clinical study designs going back and looking at the initial endpoint was 12 weeks, and it was almost a categorical endpoint of greater than 50%, but they still almost hit it. It was a p-value of 0.09, and they hit a p-value on IGA 0/1 at week 16. I think they're just whenever you commingle the use of topical corticosteroids in a study, particularly group three, it can be challenging. So I prefer personally monotherapy studies if you're really looking to understand the drug effect. But I do believe, again, I just go back to the preclinical data that we showed you. I mean, all the other competitors in this space, of course, comp against TSLP, and we took it a step further to comp against them and TSLP, and I think that residence time and all the other characteristics that we talked about are important, and I think that's how we think about this differentiation. Great. Congrats to you guys. Thanks. Thank you, Chris. Your next question comes from the line of Roger Song with Jefferies. Please go ahead. Thank you for taking the question, and congrats for this licensing deal. So quick question about the AD data. Given most of the patients, they have prior therapy, just curious about the washout period, and then given there's no placebo control in this mostly moderate patient, so do you expect the placebo effect will be similar to a moderate-severe patient? Thank you. Yeah. Thanks, Roger. Roger, Roger, and I imagine you're in London. But yeah, so prior therapy-wise, there was a considerable majority had prior therapy, whether it be topical corticosteroids, biologics, or oral drugs like JAK inhibitors. So we had a smattering of those patients who were quite exposed, and certainly there's a washout there and prior history. So I was comfortable that it was a suitable patient population to generate the signal. And relative to placebo control, you're right. Look, you always expect a little bit of that in these studies, but when you're talking about the numbers we're talking about, north of 80%-90%, particularly on some of these categorical variables, even assuming a little bit of that, it still is a very robust signal. And now it's up to us to do the phase IIB placebo-controlled and move forward. But what I like most about this opportunity is I've got the preclinical data that, again, over the last five months and even previous was done with a lot of rigor in looking at it multiple different ways and assessing it versus the competitive landscape. And now you've got this clinical translation piece with the AD study, and oh, by the way, you've got two large respiratory studies that are on the cusp of reading out in the short term. So it's quite a package to get on this first molecule. Great. Thanks. Yeah. We are in London. So maybe just quick one. Last one is regarding the next step. So understanding maybe that dosing regimen can be every four weeks. Any other considerations for the next step for the AD trial? Thank you. Yeah. We'll be providing further guidance on that in the coming weeks, but we plan to initiate that study in the first quarter this year. And so that is all in place, and we'll certainly put out that next update. Short story is three dose levels, placebo, over 200 patients, and it'll be a 24-week study with perhaps an earlier primary endpoint. Excellent. Thank you, Neal. Thank you. Your next question comes from the line of Julian Harrison with BTIG. Please go ahead. Hi. Good morning. Congratulations on getting this deal done, and thank you for taking my questions. First, I'm wondering if you could talk about the significance of steroid-free efficacy in atopic dermatitis and how much that reinforces your confidence in the early efficacy seen with BSI-045B. Yeah. I think it means a lot. I mean, having practiced as a dermatologist back in a prior life, group three topical steroids work quite well, and especially, again, in a treat-the-flare disease where there's a lot of waxing and waning. So to me, if you layer on steroids into a study like this, it makes it awfully hard to interpret. And I do think that that's also true of these placebo-controlled studies. So to me, that was a big factor. I don't know that I'd be as interested if I didn't have that fact pattern. And certainly, moving forward, we're going to be looking at monotherapy and not including topical corticosteroids because we want to understand what the drug does. We can worry about combo and layered-on treatment for the next set of studies. Okay. Great. That's very helpful, Neal. And then one of your peers in the ITK space will have early atopic dermatitis clinical data next month. I'm curious how you're thinking about the potential read-through to ATI-2138. Yeah. No. Look, we're excited. I think it's pretty unique in this environment when usually a competitive landscape has 10 to 15 assets in development, and here we have kind of three games in town. You have ritlecitinib, which is approved in alopecia areata, and then you have Corvus with their ITK selective, and we're rooting for them. But I expect that data to be good, and I think the read-through to us will be we have clearly demonstrated that we have a more potent molecule, and we have a whole franchise. So we have the initial ITK JAK3, and then we have ITK selectives behind it, and we're fortunate again to have a team that we do in St. Louis to do all this robust head-to-head testing. So we're excited about it and think this is a really interesting target that just didn't get a lot of looks because it was hard to drug. But as drug discovery technologies have evolved, we're able to get to the right place with these. So again, when you look at competitive landscapes, it doesn't get less competitive than this versus other therapy areas, which to me is exciting. Excellent. Thank you, and congrats again. Thank you. Your next question comes from the line of Alex Thompson with Stifel. Please go ahead. Hey, guys. Congrats on the deal. This is Pat for Alex. Could you guys just talk a little bit more about the bar for differentiation with this asset? And then for 502, the IND submission is planned for 1Q25. I guess how quickly do you expect to get into the clinic? Thanks. Yeah. So look, just guide you back to some of the preclinical data. I mean, that's what anybody in our position or anybody in the competitive landscape has until you get into the clinic. And the long residence time, the deep response, the durable response, if you really look at that data, you're getting about almost to eight weeks, but definitely six weeks of continuing effect. And that tells you you got nice duration without even doing a bunch of YTE stuff. I think that is the really cool feature about this molecule. When you differentiate in the clinic, you expect some of that to bleed over into the indication. You ought to see some more robust response. You ought to see more dosing flexibility. That's kind of how we think about it. Again, that's why when we first saw this asset, we really concentrated on doing all this preclinical work and doing it in triplicate, basically, and that took many months. I think it's exciting, and we clearly have a differentiation story. On BSI-502, how quickly into the clinic? Look, we're built to be in the clinic. We're good drug developers. Getting to an IND, we'll have everything prepped. We know that it takes 30 days till you hear back and you get the green light. And so we'll be in the clinic in early 2025. Awesome. Thank you. Thank you. Your next question comes from the line of Corinne Jenkins with Goldman Sachs. Thank you. Please go ahead. Good morning. This is Omari Owen for Corinne. We have a couple of questions. For the bispecific, why do you like the combo of TSLP plus IL-4 versus other potential combinations? And in the past, you've talked about seeking partners for space through development and indications like AD. Do you still view that as appropriate for the portfolio or are you inclined to get through development alone? Yeah. Let me answer the phase three question. Look, it just depends, right? There's always good reasons to get a partner for perhaps when you're engaging in very large comparative respiratory studies. I think indications like AD, we've done so many trials in that space, and we've done phase three work ourselves in other indications. So you could certainly look at that possibility, but there's always deals to be had there, and oftentimes it does make sense to pass the baton after 2B. So I would just make that comment, and then let me hand it to Hugh on the choice of IL-4 TSLP in the bispecific construct. Yeah. Hi. So when Biogen created this bispecific, there was really a very thorough review of which of the potential targets made the most sense to combine. And in fact, inhibiting IL-4 and 13 made the most sense. And so the bispecific binds to IL-4R, which neutralizes the impact of 4 and 13. While we did look at Biogen at the time, we looked at IL-13 that activating T cells, and we noticed that a bispecific of TSLP and IL-13 in our hands that we created at that time did not really activate T cells as well as IL-4. And so the decision was made to go after the receptor and inhibit both of them for maximum potency. And clearly, if you look at the COPD data by dupilumab getting an approval with a 30% reduction in AER and Tezspire in their ongoing course study with, again, roughly 30% of reduction in AER, there's a lot of room for improvement in having a bispecific that can hit both of those targets with high potency because of the same TSLP antibody in the bispecific as the monospecific. We're fully expecting that there could be a much greater upside for patients in reduction in their disease with that bispecific. Yeah. And this is just concluding comment there. This bispecific evolution is quite exciting. We're really at the front edge of all this within the market, and people are looking at different approaches. We think this makes sense. And again, I'll just congratulate the Biogen drug discovery folks. You did just a phenomenal job of constructing these molecules, and we look forward to further updates. Great. Thank you. All right. Well, operator, I think that's it for the questions, and appreciate everybody's time. And we look forward to updating you as we continue to make progress.