Aclaris Therapeutics, Inc. (ACRS) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Aclaris Therapeutics presents positive preliminary top line data for ATI-450-RA-201. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions] I'd now like to hand the conference over to your speaker today, Kamil Ali-Jackson, Chief Legal Officer. Thank you. Please go ahead, ma'am.

Thank you, Shannon. I'm Kamil Ali-Jackson, Chief Legal Officer for Aclaris. Please note that earlier today, Aclaris issued its press release announcing positive preliminary top line results from its Phase IIa clinical trial to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of ATI-450, its investigational oral MK2 inhibitor, in subjects with moderate severe rheumatoid arthritis. For those of you who have not yet seen it, you will find the release posted under the Press Releases page of the Investors section of our website at www.aclaristx.com. Joining me today for the call are Dr. Neal Walker, President and Chief Executive Officer; Dr. David Gordon, our Chief Medical Officer; Dr. Joe Monahan, our Chief Scientific Officer; Frank Ruffo, our Chief Financial Officer; and Walter Smith, our Scientific and Business Development Consultant. Before we begin our prepared remarks, I would like to remind you that various statements we make during this call about the company's future results of operations and financial position, business strategy and plans and objectives of 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, 2019, Form 10-Q for the quarter ended September 30, 2020, 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 Aclaris' website at www.aclaristx.com. All the information we provide in this conference call is provided as of today, and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events or otherwise. Please be advised that today's call is being recorded and webcast. A link to the webcast can be accessed on the Events page of the Investors section of our website. I'll now turn the call over to Dr. Neal Walker, President and CEO of Aclaris. Neal?

Thank you, Kamil. Good morning, everyone. We are pleased to present our positive results from 2 studies: RA-201, where we studied ATI-450 in patients with moderate to severe rheumatoid arthritis; and PKPD-102, where we studied 80 milligrams and 120 milligrams BID in healthy volunteers. Needless to say, we are thrilled with the outcomes. Turning to Slide 3. As a reminder, Aclaris is a biotechnology company focused on developing small molecule therapeutics for immuno-inflammatory diseases. There are 3 important aspects to help us drive important breakthroughs in the therapeutic options for inflammatory diseases. First, the people. We have world-class expertise in developing kinase-targeted medicines. Second is our platform. We have a proprietary drug discovery platform in our KINect platform. And third is our pipeline. We have an innovative pipeline that has platform potential within each of our drug candidates. Slide 4. Here's our team. We have former senior leaders from both Pfizer and GSK with decades of experience successfully developing a number of therapeutics in the immunology and inflammation space. As you can see, our current team is composed of many of the former founders of Confluence Life Sciences, which we acquired in 2017. Turning to Slide 5. Our strategic focus and the underpinnings of the company lie in our ability to leverage our kinome target discovery to address the unmet needs that continue to exist in the immuno-inflammatory space. Our fully integrated discovery team identifies key targets, utilizes our custom kinase assays to test our molecules and, within our labs in St. Louis, validates the drug candidates prior to moving to IND and clinical development. ATI-450, our MK2 inhibitor, is yet another example of an internally developed asset utilizing our KINect Platform. Turning to Slide 6. As a reminder, ATI-450 is an oral small molecule that inhibits TNF alpha, IL-1 and IL-6. There are numerous indications that are driven by the cytokines that are targeted by ATI-450, some of which are listed on this slide. These are obviously large markets with global sales in the aggregate of $77 billion. And despite great advancements over the last several years, there are still large unmet needs in these indications. We began our program with ATI-450 looking at diseases driven predominantly by TNF alpha and IL-1, which is why we initially focused on proof-of-concept studies in both rheumatoid arthritis and caps. With that, I will hand it off to Joe to describe the evolution of the MK2 program. Joe?

Thanks, Neal. p38 kinase held much promise as the central kinase in a signal transduction pathway required for the production of key inflammatory cytokines, such as TNF alpha, IL-1, IL-6 and IL-8. Despite major efforts across multiple drug companies, inhibitors of p38 kinase have not advanced through clinical development and onto the market. The 2 key issues encountered with p38 drug candidates as a class were modest transient efficacy and safety concerns. Three of the leading mechanistic hypothesis for the poor efficacy and lack of durable effect or tachyphylaxis with p38 inhibitors are as follows: The inability to dose escalate to maximum efficacy across the dosing interval, presumably due to safety concerns. Secondly, p38 inhibitors induced p38 -- induced pathway reprogramming in RA patients, resulting in p38 independent production of pro-inflammatory cytokines and apparent tachyphylaxis. And third, p38 inhibitor induced downregulation of anti-inflammatory cytokines such as IL-10, an effect that could counteract the inhibition of pro-inflammatory cytokines, resulting in lower efficacy. The finding that the p38 substrate and downstream kinase MK2 selectively drive the pro-inflammatory access of the p38 pathway while bypassing the negative feedback and anti-inflammatory access make it an exciting target and led to many pharma companies targeting MK2 in the early 2000s. But to date, no ATP competitive MK2 inhibitor has advanced to clinical development due to poor target drug ability. We have overcome the MK2 drug ability hurdle by targeting a unique pocket created upon p38 MK2 complex formation and designing a drug that selectively binds that pocket, resulting in the development of ATI-450, our current p38 MK2 complex inhibitor lead. Along with the modest efficacy and inability to dose to levels that inhibit cytokine production across the dosing interval, transient inhibition of systemic inflammation marker CRP was observed universally with p38 inhibitors in Phase II RA studies. Three examples of this transient inhibition of CRP are shown on Slide 8. p38 inhibitor dependent CRP inhibition was observed for the first 2 to 3 weeks of dosing, but levels rose with continued dosing to baseline levels by weeks 4 to 8. The key differentiators for an MK2 pathway inhibitor relative to p38 inhibitors would be a drug that is, one, safe to dose to levels that demonstrate high levels of inhibition of key cytokines across the dosing interval; and two, demonstrates durable effect on inflammation markers over 12 weeks of dosing. These were the goals of the Phase II study that David is going to describe now.

Thanks, Joe. I'm very pleased to present the data from our ATI-450 program today. As a reminder, on Slide 9, we've been running studies in RA, CAPS, COVID-19 and a high dose Phase I study. Today, we will be focused on the RA study and the new Phase I data. Slide 11 is a summary of the 201 study design. 201 was designed to discharge some of the risks associated with the p38 pathway and to investigate coming down the pathway to inhibit MK2 was the solution. Specifically, we wanted to see if a 450 dose shown to cause more cytokine inhibition in Phase I was well tolerated. And secondly, we wanted to see if it had durable activity. We planned to assess activity based on the ability to reduce hsCRP by more than 25% from baseline at all time points over 12 weeks, and we hope to see a signal on clinical efficacy assessments. We recruited patients with moderate to severe RA, with at least 4 swollen and 4 tender joints. They had to have a CRP greater than or equal to 5 and they needed to have existence of synovitis on MRI. All of that had to be present despite stable dosing of methotrexate. We randomized 3:1, and we were hoping to get at least 15 subjects through week 12. We'll be presenting the endpoint shown on the bottom of this page, with the exception of the MRI and PK data, which is not yet complete and will be part of our future manuscripts. Slide 12 summarizes the key demographics. We recruited a population with a baseline mean DAS28-CRP of 5.77 and 5.71 in the placebo and 450 arms, respectively. Since we were interested in exploring CRP reduction, it made sense to recruit patients with elevated levels of entry. But in recruiting patients with lung disease duration and elevated CRP despite methotrexate and other available drugs, we may have recruited a group of patients who are perhaps more difficult to treat or relatively refractory. 19 subjects were recruited. We had 1 dropout in each group, and I'll discuss the reasons for that later. Slide 13 is the first efficacy slide. You can see that in the active arm, there is a rapid reduction in the mean DAS-28, and that continues to decline out to day 84. The placebo group did not show a consistent change and was worse than baseline at week 12. The main drop at day 84 is 2.0 in the active arm and the median drop was 2.1. I think that puts us firmly in the range of responses you would want to see for an active drug in RA. Slide 14, I'm showing the median percent reduction in swollen joint count. The picture is very similar to what I showed on the DAS-28 and it shows a rapid reduction and continued improvement to day 84. Again, the placebo patients did not have a good response. Slide 15 shows the median percent reduction in tender joint count. Again, we see a rapid reduction and continued improvement to day 84. Consistent with other endpoints, placebo did not appear to have a marked effect. Slide 16 shows the patient and physician VAS cores. You can see that there is an improvement in the patient scores at the top of this slide. For the physician assessment of activity at the bottom, you can see there is a marked improvement, which is maintained over the full 12 weeks of the study. Slide 17 shows the ACR20, 50 and 70 scores. There was a rapid increase in the proportion of ATI-450 patients meeting ACR20 criteria at day 28. And by day 84, that proportion has increased to 60%. By day 84, 33% of 450 subjects had hit the ACR50 and 20% met the ACR70 criteria. No patients in the placebo group hit these endpoints. With 60%, 33% and 20% of patients hitting the ACR20, 50 and 70, it looks like ATI-450 is delivering efficacy that you would hope to see in an active and effective drug. Slide 18 shows the responder analysis for the DAS28 scores. A DAS28 less than 2.6 represents remission, and that was achieved in 20% of 450 subjects. A DAS28 of less than or equal to 3.2 represents low disease activity and 40% of 450 subjects achieved that. No placebo patients met this endpoint. Like the ACR scores, I think this responder rate compares well with the efficacy shown by other active drugs. Slide 19 shows the median percent change in hsCRP. As a reminder, our hope was that we would reduce the CRP by at least 25%, and that's shown here by the dotted line. And that would represent a marked deviation from what was shown in the p38 inhibitors. You can see on this slide that the ATI-450 arm reduced the median CRP by at least 40% at all study [ visits ] and placebo did not show a sustained reduction. This profile supports the sustained efficacy that I showed on previous slides. Moving to Slide 20. We have cytokine data to support the clinical responses, and I'll pass the mic to Joe to take us through that, beginning on this slide.

Thanks, Dave. One of the hypothesis to explain the lack of durable efficacy with p38 inhibitors as a class in RA studies is that dosing RA patients with p38 inhibitors over 12 weeks results in signal pathway reprogramming and inhibitor induced p38 pathway independent cytokine production with time. This analysis was designed to ask the question, will administration of ATI-450 for 12 weeks in RA patients result in a sustained inhibition of pro-inflammatory cytokines? Blood was analyzed from RA patients on day 1 of dosing and day 84 of dosing following ex vivo stimulation with LPS and evaluated for the ability of ATI-450 to inhibit TNF alpha and IL-1 beta compared with placebo. Focusing on the third and fourth bars in each group, the data clearly demonstrate that ATI-450 almost completely inhibits TNF alpha on the left on day 1, and that inhibition is maintained through day 84. And similarly, on the right, ATI-450 inhibition of IL-1 beta is comparable on day 1 and day 84. This analysis provides evidence that inhibitor dependent pathway reprogramming is not observed with the MK2 inhibitor ATI-450 over 12 weeks of dosing and a durable inhibition of inflammatory cytokines is observed, consistent with the durable reduction of CRP that David talked about. On Slide 21, we turn to look at the impact of ATI-450 on endogenous cytokine levels in plasma from these RA patients across the 12-week dosing period. Three pro-inflammatory cytokines from the 13-plex analyzed are shown on this slide, TNF alpha, IL-6 and IL-8, along with the chemokine MIP-1 beta. The data are expressed as [ mean ] percent change relative to pre dose levels for drug-treated patients. Samples were evaluated at trough drug levels after 4, 8 and 12 weeks of dosing as well as peak levels 4 hours after the final dose on day 84. The horizontal line describes analyte levels in plasma from normal subjects. TNF alpha concentrations are significantly reduced after 4 weeks of dosing, and this reduction is maintained through the 12 weeks and approaches levels of the cytokine present in healthy volunteers. Similarly, IL-6, IL-8 and MIP-1 beta levels are reduced at week 4, and this reduction is maintained through the 12 weeks of the study. This analysis provides additional supportive evidence consistent with the data presented thus far, demonstrating durable anti-inflammatory activity of ATI-450 in RA. And I'll pass back to David to Slide 22 to describe the safety.

Thanks, Joe. So here on 22 are the adverse events that were reported in the study. The drug was generally well tolerated, and we had no serious adverse events or any severe events either. This slide shows the adverse events that were reported by at least 1 subject. We had no reports of dizziness in the study. I'll leave that there to let you read that, while I'll tell you about the withdrawals that we had during the study. One subject in the ATI-450 group had a CPK elevation that was associated with palpitations at the study visit. As a result of that combination, the investigator elected to hold drug and refer to a cardiologist. The cardiologist completed a thorough evaluation of the subject and excluded an acute cardiac event. We could have reentered the subject to the study, but he'd been off drug for over a week by the time of the assessment, so we elected not to. One subject in the placebo group required a steroid injection for a musculoskeletal event. Since that was a prohibited medication, we withdrew that subject. As you can imagine, we're very pleased with the results of 201. We believe that this study supports our belief in the potential for 450 to treat immuno-inflammatory diseases. I'd like to shift gears now beginning on Slide 24. Given that ATI-450 was well tolerated at 50 milligrams BID, we decided to conduct an additional MAD study exploring doses higher than 50 milligrams BID. As a reminder, Study 101 demonstrated that 450 was well tolerated with good kinetics up to 50 milligrams BID. We also established that 50 milligrams BID achieved trough drug levels above the IC80 for TNF alpha, IL-1 and IL-8 and above the IC50 for at least part of the dosing interval for IL-6. In the 102 study, we replicated the MAD component of 101 with doses of 80 milligrams BID and 120 milligrams BID. The cohorts had 8 active and 2 placebo patients each, which were the same size as study 101. Slide 25 presents the PK profile of both studies combined. We see nice dose proportionality between 10 and 80 milligrams BID, but not much increased exposure as we move to 120 milligrams BID. The half-life of 450 in all treatment arms was between 9 and 14 hours, suggesting that 450 has potential to be a once-daily drug. The cytokine data from this study is very interesting, and I'd like to pass back to Joe to lead you through that.

Thanks, Dave. So going to Slide 26. The data on the next 3 slides summarize the pharmacodynamic marker analysis from the combination of all the MAD cohorts from both the 101 and 102 studies, evaluating ATI-450 at 5 different doses from 10 to 120 milligrams BID along with placebo in volunteer subjects over 7 days. Blood from these subjects was collected at the indicated times, ex vivo stimulated with LPS and analyzed for key biomarkers. The data on the left shows level of target biomarker phosphoHsp27 and the inflammatory cytokine TNF alpha following 7 days of dosing at peak drug levels, 4 hours post-dose, and trough levels, 12 hours post-dose relative to the day 1 pre-dose. A near complete inhibition of both markers is observed at day 7, 4 hours post-dose, and the inhibition is maintained across the 12-hour dosing interval. The dose dependency of ATI-450 at 4 hours post-dose is shown on the right. The 50-milligram dose used in the RA study is the third to last bar and an incremental increase in biomarker inhibition is observed with the 2 higher doses of 80 and 120 milligrams evaluated in the MAD 102 study. On Slide 27, the inflammatory cytokines IL-1 beta and IL-8 were analyzed and a comparable dose-dependent and sustained inhibition was observed across the dosing interval on day 7, with incremental increased inhibition in the highest dose groups. And finally, on Slide 28, IL-6 demonstrates the same pattern, with sustained inhibition across the dosing interval observed at the highest dose groups. Taken together, these data demonstrate the potential of doses higher than the 50-milligram dose used in the current RA study to treat patients with autoimmune and chronic inflammatory diseases. p38 is known to modulate the anti-inflammatory cytokine IL-10, thereby potentially limiting inhibitor anti-inflammatory efficacy. As shown on Slide 29, we evaluated the impact of ATI-450 in IL-10 production. Analysis of the blood taken from subjects in the 80- and 120-milligram Phase I MAD cohorts on day 7, 4 hours after the final dose was carried out following ex vivo LPS stimulation to evaluate the impact of ATI-450 and IL-10 levels relative to the anti -- relative to the pro-inflammatory cytokines TNF alpha and IL-1 beta. In contrast to the near complete inhibition of TNF alpha and IL-1 beta, the middle and right set of bars, IL-10 on the left only inhibited approximately 30% at these high doses. These data suggest that, one, ATI-450 strongly favors inhibition of proinflammatory cytokines relative to anti-inflammatory cytokines, in contrast to what has been hypothesized for p38 inhibitors; and two, selectivity for the pro-inflammatory cytokine inhibition is maintained with ATI-450 at these high doses and corresponding exposures. Finally, on Slide 30, we asked the question how effectively does ATI-450 inhibits cytokines induced by a different ex vivo stimuli, potentially more relevant to autoimmune disease? For this analysis, we utilized IL-1 beta stimulation in parallel with the LPS stimulation, as IL-1 beta is a cytokine that has demonstrated involvement in chronic inflammatory diseases such as RA. The data presented as a comparison of ATI-450's efficacy for inhibiting 3 key cytokines: TNF alpha; IL-6; and IL-8, following ex vivo stimulation with either LPS or IL-1 beta of blood from subjects dosed for 7 days with 80 or 120 milligrams of drug BID. Compared with the pre dose and placebo, similar high levels of inhibition are observed with TNF alpha on the left-hand panel with both stimuli. Interestingly, comparable or potentially greater ATI-450 inhibitory efficacy is observed for IL-6 in the center and IL-8 on the right following IL-1 beta stimulation compared with LPS stimulation. These data provide confidence that inflammatory cytokine regulation by ATI-450 is not stimulus-dependent and that this inhibitor may have broad applicability across inflammatory diseases. Dave will now describe safety in this study.

Thanks, Joe. So Slide 31 reports the adverse events in the 102 study. The safety of doses up to 120 milligrams appear to be good with no dose-limiting toxicity. We saw no serious adverse events or labs that were of concern in this study. There are more patients with dizziness in the 120-milligram group, and that was generally a lightheadedness that has coded to dizziness. It was mild and didn't stop any day-to-day activities. In all 6 subjects in the 120-milligram cohort, the dizziness resolved while still taking drug. So if this is a true drug effect, it's something that we could warn patients about as a transient early event. As I mentioned earlier, we didn't see any dizziness or lightheadedness reported in the RA study. The headaches all happened in the first 2 days of dosing and were not seen after that. In conclusion, on Slide 32, I think we've achieved what we set out to deliver. The ATI-450 deliver durable efficacy as defined by DAS28 reduction, the joint scores and the ACR responses which improved early and continued to improve over time. Our original aim to reduce CRP by at least 25% from baseline was exceeded. The disease activity scores that were achieved, the ACR20/50/70 of 60%, 33% and 20%, represents important improvements in RA with the magnitude of response that you would hope to see. The additional Phase I data allows us to explore higher doses in the next stage of development. We firmly believe that we've delivered the data to provide confidence to move into the next stage of development of ATI-450. As a result, we've already started our Phase IIb plans, and we're moving forward with this program. I'll now pass back to Neal for concluding comments.

Thank you, Dave, and thank you, everyone, for joining us today. There are a lot of reasons to be excited about ATI-450. First, it's a new mechanism, and we're first-in-class. Second, it's an oral that targets cytokines traditionally targeted by biologics. Third, because we hit more than 1 key cytokine, we have the potential for a synergistic effect. Fourth, there's potential for daily dosing, given the half-life that we've already demonstrated across all of our studies. Fifth, this is an opportunity to have a pipeline in a product. There are numerous indications that one can go after when you look at the targets that we're suppressing. And then lastly, what we have demonstrated thus far is what we believe to be a favorable safety profile. As such, we believe we have an important new therapeutic for the treatment of not only RA, but a wide variety of diseases that are driven by TNF, IL-1 and IL-6. We are very excited to move ATI-450 to the next stages of development. I would really like to thank our team in both St. Louis and Wayne for all of the hard work, particularly during these challenging times. At this point, I'll pass it off to Shannon, who can poll for questions.

[Operator Instructions] Our first question comes from Louise Chen with Cantor.

Congratulations. I had a few. First question I have for you is what type of efficacy and safety do you think you might see in the higher doses, the 80 and 120 and as you extend over 12 weeks of treatment? Second question I had is, in addition to this once-a-day dosing, what are the potential competitive advantages do you see? For example, can it be used in combination? Are there any read-throughs to any of your other studies that are happening and ongoing? And the last question I had is, if your drug is approved, where would it fit into the treatment paradigm with biologics and JAKs that are already approved?

Okay. Thanks, Louise. Appreciate the questions. So for -- in terms of the positioning and the fit, we -- there's still a lot of room within rheumatoid arthritis. There's obviously been a lot of great advancements in the space. And we see opportunities given the profile, the relative efficacy and safety that we've already demonstrated, to look at not only potentially monotherapy or earlier treatment of disease but also combo treatment, particularly given the safety profile. I think it's pretty well-known that polypharmacy is the rule in this indication. And we haven't even begun to tease out those patients who kind of rotate off of TNF alphas. It used to be that patients would go from one TNF alpha to the next. And there's a lot of cycling or churn in this disorder. Certainly, patients end up being on multiple medications. And I think we've seen with the launch of RINVOQ that there's actually been a lot of switching from the TNFs into JAK inhibitors, in particular, because of the oral dosing. So I think the oral dosing is a big advantage, the ability to potentially do QD. And then, again, kind of the relative safety profile. And also looking at the ability to hit multiple cytokines. So often, when you look at some of the biologics, they target 1 particular cytokine, and we're obviously hitting 3 of them quite potently. And we believe that there is a synergistic effect there. And in terms of your first question on the efficacy and safety, higher doses and extending the time period. So that's exactly why we wanted to include the PK/PD information in this deck. We certainly believe that the safety profile and the incremental suppression of cytokine supports going higher. We've got a lot of headroom in this study. We looked at 50 BID and we clearly demonstrated that we can go up to 120 milligrams BID. And in terms of the -- your question about longer treatment. I mean, obviously, if you look at the graphs, the curves keep going down. So we're assuming that there'll be continued improvement over time. I mean, that remains to be seen. We have to do the work. But certainly, all the trends look like that would be the case, and we're excited to proceed to the next levels in those studies.

Our next question comes from Tim Lugo with William Blair.

Congratulations on the data. Really impressive work. With tachyphylaxis, obviously, normally the issue in this pathway, it seems like we're seeing kind of a deepening of responses in almost all the clinical measures. Can you maybe just discuss the length of the next Phase IIb and how you'll explore beyond 12 weeks? And for the next study, I know you're figuring out as we speak. But can you just briefly talk about doses. It looks like 80 mg BID is nice and clean and additional cytokine suppression. But incrementally, I'm not sure the cytokine suppression data of 120 looks to be significant over 80 mg. And it does seem like you have this dizziness signal. So can you just maybe talk about those?

Sure. So taking that last question first. So just as a reminder, we saw no dizziness at all in the 12-week RA study. So certainly, it was in the Phase I unit. Not sure what to make of that since it is quite transient and didn't interfere with any activities. It didn't interrupt dosing. And again, in kind of a more real world study, we saw -- we didn't see it at all. So I'm not particularly worried about that in the least. And I think from my perspective, the RA study trumps what we saw in the Phase I unit. In terms of the deepening of responses at 12 weeks. Certainly, as we continue our program, and we're in that process of getting the design of this study all wrapped up. And it's certainly going to be 12 weeks, and we'll also look at kind of open-label extension, portions of it. And so that's not been totally decided, but I think it would behoove us to continue to press the duration of treatment here, and we look forward to rolling out a comprehensive Phase IIb program in the near term. And this will be, I think, a traditional multi-arm study where we're looking at a few different doses and potentially also exploring the QD dosing aspect.

Okay. And maybe briefly, can I just hear your updated thoughts around business development. And I assume there's going to be a number of larger companies also intrigued by the data. Can you just remind us what an ideal partner would look like for developing this asset or if you want to just push it through Phase IIb where you could build even more value given the strength of today's data?

Yes. So we -- as you can imagine, we don't typically comment on BD. I think looking at the breadth of indications that one can go after with this molecule, given the fact that we potently inhibit TNF, IL-1 and IL-6, I do think that exploring different partnerships is an option on the table. But at the moment, we're continuing to operate with moving Phase IIb forward.

[Operator Instructions] Our next question comes from Thomas Smith with SVB Leerink.

Congrats on the data. First, I guess, a couple of questions on the RA data set. I understand you're still in the process of analyzing the data, but can you comment at all, I guess, even qualitatively, on some of the imaging data you've collected? And then on the 1 ATI-450 patient withdrawal, can you just comment, did this patient have any history of palpitations or was the patient on any background meds? Or were there any other notable confounding factors with this particular patient?

Sure. So we don't have the MRI data yet, so I can't comment on that. But as a reminder, that was predominantly used as a screening tool because we wanted to make sure that the patients who were screened in actually had active disease. And that encompassed both inflammation of the synovium, but also pretty good joint erosion. And as Dave mentioned earlier in our presentation, these were pretty hard-to-treat patients. And so you can imagine, the joints were pretty advanced. But we look forward to presenting that in a future publication. Regarding the other patient, I'll hand that off to Dave to just describe that patient [ med ] withdrawal.

Yes. Thanks. So that patient, I think, is 61. He did have some elevated lipids coming into the study but was otherwise pretty fit and well. He did have the palpitations and the elevated CPK that led to the cardiologist referral. He had a thorough workup by the cardiologist and, as I said, discharged from having any cardiac event. And then just maybe additionally, reassuring was that when we assessed the CK-MB portion of the CPK elevation, it confirmed that the elevation of the CPK was not coming from the myocardium. So it was musculoskeletal. Musculoskeletal -- I think the rise -- he was slightly elevated at baseline when he came in, and he didn't go more than 3 -- between 3 and 4x baseline. And when you speak to rheumatologists in the area, they would describe that as being a very typical finding that you look at in these patients. So I don't -- there wasn't any cardiac event, yes.

Got it. Okay. Yes. I appreciate the additional color. And then I guess, also, in the initial SAD/MAD study, you noted a decrease in absolute neutrophil count. Can you comment on patient neutrophil levels in this study?

Yes. So I looked at the neutrophils in all the individual patients. There is a little bit of a trend in decrease in neutrophils, as you'd expect. I think it's in keeping with the pharmacodynamic effect of the drug. But no one became neutropenic in study. No one dropped to levels of neutrophils routes that would have been of any clinical concern.

And I currently show no further questions at this time. I'd like to turn the call back over to Neal Walker for closing remarks.

Well, thanks, everybody, for joining us. Obviously, as I mentioned before, the team is thrilled. And I want to again thank our team, the patients, the investigators who participated in this trial. Particularly during a pandemic, it wasn't easy. We were able to get this study done right on schedule, and we really appreciate everybody's patience with us and look forward to next steps. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.