Incyte Corporation (INCY) Earnings Call Transcript & Summary

Greetings, and welcome to the Incyte Investor Update Call. [Operator Instructions]. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Pablo Cagnoni. Please go ahead.

Thank you, Kevin. Good morning. I'm pleased to welcome you to Incyte's conference call highlighting the 2 positive Phase III clinical trial results of povorcitinib in patients with hidradenitis suppurativa, a chronic inflammatory skin condition characterized by painful nodules and abscesses on the skin that can lead to irreversible destruction and scarring. Before we begin, I encourage everyone to go to the Investors section of our website to find the press release and slides for today's discussion. On today's call, I'm joined by Joslyn Kirby and Steven Stein, who will deliver our prepared remarks. Herve, Christiana and Jim will also be available for the Q&A. During the call, we will be making forward-looking statements, which are based on our current expectations and beliefs. The statements are subject to certain risks and uncertainties, and our actual results may differ materially. Please consult the risk factors discussed in our SEC filings for additional detail. 2025 is set to be an inflection year for Incyte, marked by a number of defining catalysts across each of our programs as highlighted on this slide. We anticipate 4 product launches, which collectively offer substantial near-term revenue potential. Notably, the launch of Niktimvo is already underway. In addition, we plan to initiate at least 3 Phase III studies, including our BET inhibitor as monotherapy in second-line myelofibrosis, ruxolitinib cream for mild to moderate hidradenitis suppurativa and our CDK2 inhibitor in ovarian cancer. 2025 is also expected to be a data-rich year with 4 pivotal data readouts on the horizon. Today, we have disclosed positive bioequivalence data for ruxolitinib XR and positive top line results for ruxolitinib cream in prurigo nodularis. With today's announcement of positive Phase III results for povorcitinib, we have successfully achieved 3 of these critical data milestones. Importantly, we anticipate that 7 early-stage programs will yield proof-of-concept data, which we believe have the potential to transform our pipeline. We are excited to share additional updates as the year progresses. Now I'm pleased to introduce Dr. Joslyn Kirby, who recently joined Incyte, and will be providing an insightful overview of hidradenitis suppurativa. Dr. Kirby is a world-renowned dermatologist and researcher specializing in chronic inflammatory skin conditions with a particular focus on hidradenitis suppurativa. She has served as the former President of the HS Foundation, underscoring her leadership and expertise in the field. Dr. Kirby joins us for Penn State Health, where she continues to treat patients with hidradenitis suppurativa in her clinic. Her research has resulted in hundreds of publications and the development of several outcome measures for HS, some of which are integral to our Phase III studies. Contributions to the field are invaluable, and we're thrilled to have her expertise at Incyte. With that, I'm delighted to turn the call over to Joslyn.

Thank you, Pablo. We'd like to share an overview of the HS, highlighting the unmet needs and opportunities for treatment with povorcitinib, a selective JAK1 inhibitor. HS was once thought to be rare. However, more recent prevalence estimates suggest HS affects approximately 1% of people in the U.S. and Europe. It has a [indiscernible] distribution with peak onset in the third decade. Females are 3x more likely to be affected than males and similarly, black or biracial patients have higher odds of HS. While prevalence estimates have increased over time to approximately 1%, there continues to be a 7- to 10-year diagnostic delay. HS is a chronic inflammatory condition characterized by inflammatory nodules, abscesses and tunnels, which can eventuate into open sores and scars with this damage accumulating over time. The vast majority of patients report a flare, which is a worsening of lesions and symptoms each month or even more frequently. One of the treatment goals is to reduce flare frequency and severity. During flares and often between flares, patients experience pain, itch, drainage and fatigue, with pain being the most prominent symptom. And not surprisingly, it is significantly associated with reduced quality of life. Pain is the most prominent symptom of HS, in part because it is pervasive with nearly all patients experiencing some amount of HS-related pain. The pain can vary in character as well as intensity, but is often rated as moderate to severe, as shown on the right. Among skin conditions that cause pain, HS has been shown to be one of the most severe. Much has been learned recently about the pathogenesis of HS. In contrast to other dermatoses where a single axis of the immune system is dominant, hidradenitis is more complex and heterogeneous with multiple cell types and cytokines implicated. This may explain the limited efficacy of some therapies since the approved therapies are all injectable monoclonal antibodies specific to certain interleukins. In contrast, JAK1 inhibition is involved in the signaling across multiple cytokines and across disease stages. As a small molecule, povorcitinib is also differentiated by its oral administration. As a highly selective JAK1 inhibitor, povorcitinib can modulate multiple cytokines involved in HS pathogenesis, as shown on the left in green. This high selectivity for JAK1 and sparing of JAK2 on the right, avoids hematologic events during treatment. Povorcitinib has demonstrated best-in-class in vitro selectivity for JAK1 over JAK2 and enzymatic assays, where selectivity for JAK1 is approximately 50x higher than JAK2. These findings were confirmed in whole blood assays, which are more representative of the in vivo setting. In whole blood assays, povorcitinib selectivity was 16x higher for JAK1 than JAK2. In contrast, less selective molecules had selectivity for JAK1 that was only 1.6 or 1.2x higher than JAK2, raising the potential concern for more JAK2 activity and hematologic events during treatment. Povorcitinib has differentiated pharmacokinetics. These are data from a study of healthy volunteers who took povorcitinib 75 milligrams daily for 10 days. Subsequently, both blood and skin samples were taken to assess povorcitinib concentrations over time. Plasma levels in orange and skin levels in turquoise quickly reached peak concentrations of approximately 3x the IC50 for JAK1. The PK curves for both skin and plasma are well below the IC50 for JAK2 and both curves overlap, demonstrating that povorcitinib reaches the target tissue efficiently, which is aligned with its high volume of distribution. Additionally, the therapeutic levels are sustained above the JAK1 IC50 for approximately 2 days after the last dose, highlighting that povorcitinib delivers a true once-a-day pill without the need for an extended release formulation. The current treatment of moderate to severe HS is extremely challenging, with 45% of patients who are on a biologic reporting treatment dissatisfaction. Approved therapies are all interleukin-specific monoclonal antibodies. And povorcitinib is an important addition with a mechanism of action that addresses multiple cytokines involved in HS pathogenesis, delivers rapid results and the convenience of an oral therapy. Incyte is uniquely positioned to bring new treatments to the entire spectrum of HS severity with our plans for pivotal Phase III studies of ruxolitinib cream in mild to moderate HS, and povorcitinib for moderate to severe HS. And without further delay, Steven will now share the top line results of the STOP-HS1 and 2 trials.

Thank you, Joslyn and good morning, everyone. This morning, I have the pleasure of presenting the povorcitinib Phase III study results on behalf of the patients who volunteer for our studies and the investigators who conduct them. STOP-HS1 and HS2 are identical in design and together encompass 1,227 adult patients. These were global studies conducted in 200 sites around the world. Eligibility required patients to have moderate to severe HS with an abscess nodule count greater than or equal to 5 in at least 2 anatomical sites. Patients also had to have an HS diagnosis for at least 3 months. Concomitant antibiotic use for HS was not allowed. Stratification factors were the abscess nodule draining tunnel count and prior biologic use. The primary endpoint was HiSCR50 at week 12, which balanced the time patients would be on placebo as well as the ability to demonstrate the rapidity of response for povorcitinib. Patients will be followed at the visit frequency on the slide through 54 weeks. Randomization initially was 1:1:1 for placebo, povorcitinib 45 milligrams and povorcitinib 75 milligrams. At week 12, the placebo arm was rerandomized to 45 milligrams and 75 milligrams. The other treatment arms continued their assigned dose. The key secondary endpoints are HiSCR75 at week 12, greater than or equal to a 3-point reduction in skin pain NRS at week 12, skin pain NRS30 at week 12, and flare by week 12. In terms of demographics and baseline characteristics, they were well balanced across arms and studies. The mean age range from 36 to 39 years old and gender 54% to 68% were female, while 68% to 80% of patients were white. The mean BMI was 33 to 35. The duration of prior HS was 9.7 to 10.8 years. Hurley III constituted 29% to 42% of patients and the mean abscess nodule count at study entry was 11 to 13. Prior biologic exposure was 35% to 39%. The primary endpoint of HiSCR50 was clinically and statistically significant for both doses in both studies. Specifically, STOP-HS2 had a placebo-adjusted difference of 13.8 for both doses and STOP-HS1 were 10.6 for 45 milligrams and 10.9 for 75 milligrams, all statistically significant and clinically meaningful. Slide 19 looks at the HiSCR50 response by prior biologic exposure in a predefined analysis and povorcitinib demonstrates a greater differential efficacy in patients previously treated with biologics. Specifically in STOP-HS2, the difference versus placebo in the 45-milligram arm was 25.5% and in the 75-milligram arm was 20.5%. In STOP-HS1, the difference versus placebo in the 45-milligram dose was 12.3% and in the 75-milligram dose was 15.9%. In a pooled analysis for each dose, the HiSCR50 response at week 12 difference for povorcitinib 45 and 75 versus placebo was 19.1% and 18.3%, respectively, in patients previously exposed to a biologic. While povorcitinib has demonstrated strong efficacy regardless of prior biologic use, in practice, many patients will be expected to have experience with biologics and this average placebo-adjusted difference of 19.1% and 18.3% in comparable efficacy in the predefined subgroup is highly meaningful. On Slide 20, HiSCR75, a key secondary endpoint. In STOP-HS2, the difference in the 45-milligram arm versus placebo was 12.3% and in the 75-milligram arm, 15.1%, both were statistically significant. In STOP-HS1, the difference in the 45-milligram arm versus placebo was 4.8 and the 75-milligram arm, 8.5, with a p-value here being 0.03. Our stringent multiplicity testing was set at 0.025 for the 75-milligram arm and hence, all other secondary endpoints in the STOP-HS1 study are thus nominal p-values. Slide 21 shows the greater than or equal to 3-point decrease in skin pain NRS and demonstrates the rapid onset of pain reduction. In STOP-HS1, the 75-milligram arm at week 12, 22% of patients achieved this and in the 45-milligram arm, 17%. In STOP-HS2, the 75-milligram arm was 22% and the 45-milligram arm, 29%, both statistically significant and again, highly clinically relevant. Looking at skin pain NRS30 on Slide 22, povorcitinib again demonstrates the rapidity of pain relief versus placebo. In STOP-HS1, the 75-milligram arm had 35% achieved this and the 45-milligram arm, 32%. In STOP-HS2, the 75-milligram arm at 38% achieved this and in the 45-milligram arm, 41%, again, both statistically significant and a very important demonstration of rapid symptom relief for patients. Addressing patients' pain as rapidly as possible is critically important in terms of improving the impact of this condition on patients' lives. Slide 23 shows the clinically meaningful reduction in flare by week 12. Specifically in STOP-HS2, flares were reduced by 13% at the 75-milligram dose and by 12% at the 45-milligram dose, both doses demonstrating statistically significant and clinically important outcomes for patients. In STOP-HS1, flares were reduced by 9% with the 75-milligram dose and 7% with the 45-milligram dose. Moving to Slide 24, and the overall safety summary during the placebo-controlled period. It is very reassuring that other than acne, there are no safety differences for patients treated with povorcitinib compared to the placebo arm. On Slide 25 are the adverse events of special interest. And very importantly, there's no evidence of MACE, malignancy or thrombotic events during the placebo-controlled period. There were 2 malignancies reported overall in the 2 studies, both of which were in the placebo arm and STOP-HS2. In STOP-HS1, there were 4 serious infections on placebo and 2 on 75 milligrams. And in STOP-HS2, there were 2 serious infections on placebo and none on povorcitinib. This is a very compelling safety profile for povorcitinib at this juncture. In summary, on Slide 26, the primary endpoint was met in both STOP-HS1 and HS2 for both povorcitinib doses evaluated. Greater differential efficacy was seen in patients who are biologic exposed. In a predefined pooled analysis by dose, the HiSCR50 response at week 12 for povorcitinib 45 and 75 milligrams versus placebo was 19.1% and 18.3%, respectively. The key secondary endpoints demonstrate deep response and rapid reduction of skin pain, and the safety profile is manageable with a well-tolerated drug. We will continue to follow the patients per the study visit frequency and present additional data as they evolve at upcoming medical conferences this year. We anticipate filing an NDA for povorcitinib for the treatment of adults greater than or equal to 18 years of age with moderate to severe HS sometime between late 2025 and early 2026. With that, I would like to turn the call back over to Pablo for his closing remarks.

Thank you, Steven. With this result, povorcitinib is now on track to become the first orally available treatment for hidradenitis suppurativa, offering patients a convenient treatment option with rapid and substantial relief of the painful manifestations caused by HS. The results of the STOP-HS1 and STOP-HS2 studies confirm the excellent safety profile of povorcitinib observed not only in patients with HS, but across all indications in development, including vitiligo and prurigo nodularis. Furthermore, previously reported Phase II data in HS demonstrate that continued use of povorcitinib leads to deepening of responses over time. We continue to advance a comprehensive development plan for povorcitinib beyond HS with Phase III studies ongoing in vitiligo and prurigo nodularis alongside 2 randomized Phase II proof-of-concept studies in chronic spontaneous urticaria and asthma, with both proof-of-concept data readouts anticipated in 2025. Povorcitinib represents a transformative opportunity for Incyte with the potential to drive significant growth. The success of this program hinges on 5 key differentiating factors. First, povorcitinib has the potential to be best-in-class oral JAK inhibitor. Second, it has an excellent safety profile observed thus far. Third, povorcitinib's JAK1 selectivity and differentiated pharmacokinetic profile distinguishes it from other agents. Fourth, it allows for a seamless commercial transition within our established dermatology infrastructure. And lastly, it holds significant potential across 5 indications currently under evaluation, all representing diseases where patients are lacking effective treatment options. 2025 is poised to be an important year for Incyte, marked by over 18 catalysts that underscore our commitment to innovation and growth. The positive Phase III results of the STOP-HS1 and STOP-HS2 studies presented today represent the first pivotal results for povorcitinib and will lead to worldwide regulatory submissions for the treatment of patients with hidradenitis suppurativa. Operator, this concludes our prepared remarks. Please proceed with your instructions and open the call for Q&A.

[Operator Instructions]. Our first question today is coming from Michael Schmidt from Guggenheim.

I had a question perhaps for the physician on the call. Could you talk about how these top line results for povorcitinib and the overall profile perhaps in HS position the drug relative to the biologics that are on the market? And what percentage of patients do you think would ultimately be candidates for this therapy in your opinion?

This is important information for, I think, many of the clinicians and patients who are managing HS. The importance of this data mean that we now have a new tool in our toolbox to treat this really challenging condition. We make the decision of treatment not only on the basis of the efficacy of a therapy, but also on the basis of other comorbidities that a patient may have, which might make other biologics a less excellent option as well as on the basis of the safety for a given molecule. Overall, there's a greater number of patients with HS who are, number one, being correctly diagnosed and number two, getting appropriate therapy rather than staying on antibiotics for an excessive period of time. And given the pathogenesis of this inflammatory condition, it is very important to move them appropriately when they have moderate to severe disease onto an immunomodulating therapy such as povorcitinib or biologic. The data that we have in hand, I think, gives us a lot of excitement about changing the therapies for people with HS.

Next question today is coming from Tazeen Ahmad from Bank of America.

Okay. Great. This is also for the physician. If you have to compare it to other treatments available right now in the market to treat patients versus one that could also come on to the market, what percent of patients do you think you would recommend this drug to today? And then if I could, could I ask the Incyte team what the gating factors are remaining for the filing of the sNDA because you said you're not going to potentially get to that until end of this year or early next?

Okay. Tazeen, let me first have Steven answer the second part of the question about getting factors for submission and then Joslyn will comment on your first part.

Yes. Tazeen, it's Steven. So as we showed in the study schema, the study goes on for 54 weeks. After week 12, the treatment arms continue in the placebo arm are re-randomized. And as we also said, we commit to updating those data sets. From a safety point of view, regulatory agents are interested, obviously, in long-term safety. We need to meet with the FDA and sit down and negotiate what that package will look like, which is why we gave a range. We know already about 60% of patients have gone through week 24. So we're on track. And that's why it could be potentially at its fastest by the end of this year into early next year. But we'll sit down with the FDA and get precision on that timing pretty soon.

Related to patient profiles and the selection of therapies, like I mentioned, this is really based off of when we're seeing patients in clinic, there severity of disease, the degree of pain, the amount of speed that we might need out of improvement in that disease. It's also about other comorbidities that we might be trying to avoid exacerbation of or perhaps complementary mechanism of action. And again, the safety. But another big factor that I hear from many of my patients is they're not looking for an injection. And so the delivery or administration of povorcitinib as an oral versus some of the biologics, that is definitely a part of the conversation with patients.

Next question is coming from David Lebowitz from Citi.

When you have a patient -- new patient coming into practice, and you are opposed with this data for the oral versus the data we've seen to this point with the biologics. What goes to your decision-making process in determining how you choose the biologic or the oral for their first option?

Yes. Thanks for your question. So the decision-making process is, for many of us, very closely aligned with the patient's kind of wants. And so we're hearing from them what the impact of this really sometimes very debilitating disease is on patients. I talked a lot about pain, and that is really a very big part of the, I think, decision-making when we're offering these therapies to patients, moderate to severe, how quickly can I feel better? How much improvement am I going to get? And then, of course, how do I use it? So is this something that I have to inject myself with or get help from a family member? Is it a pill that I can take? And what risks do I take on from that therapy. So it's really a number of factors that in combination with the patient are taken into account.

Maybe a quick addition to the commercial aspect of this. I mean, obviously, in 18 months or when we'll be launching this product, most patients will have been exposed to biologics. So that's something to take into account. I mean, the flow of new patients are obviously naive and that's what we are speaking about. And they're having an option with fast pain release is valuable for some of them. And then you have what is most of the patients in number who have been exposed to biologics and where this study, in fact, is showing that there is a differentiated efficacy profile on top of the pain or aspect and some of the other secondary end points. So that's one thing to look at. In some countries outside of the U.S., reimbursement would be for patients pretreated with biology. So that's where we can see here that the efficacy is the strongest. And in the U.S., we know already there are payers who are requiring use of a biologic before going to the next line of treatment. So in some way, the way this data ended up showing is very much aligned with what we think is a very good commercial profile for what the actual unmet medical need will be in 18 months.

Next question today is coming from Jessica Fye from JPMorgan.

Maybe kind of following up on this topic around where the product could be positioned in biologic naive versus experienced patients. Do you think the label for povo will include biologic naive or be confined to biologic experienced patients? And then do you think the data for the biologic experience subgroup could get on the label?

Jessica, this is Pablo. Look, I think the most important thing here is to first look how the study was designed. The study was designed in all comers, both with and without prior biologics -- biologic exposure. And the results of the study, as Steven summarized, are not only statistically significant, but clinically meaningfully improving a range of endpoints, including a very fast relief of pain in patients with hidradenitis suppurativa. So based on that, we obviously intend in the U.S. to seek a broad label with and without prior biologic exposure. We presented the biologic exposure data because of 2 key points. One, it was a stratification criteria in the study; and b, we recognize that there are biologics on the market today, and we wanted to have that data because we think a certain percentage of patients may elect to start with the biologics. But as we see it today, based on the profile from the 2 studies and based on the data that we have in hand, the drug should be used in pre or post biologics patients. So a broad patient population. In terms of what label we'll get, I think that will be a conversation we'll have later after we had an opportunity to discuss this with the FDA. But we intend to seek a broad label because the results of the study and intent-to-treat analysis show a broad treatment effect across both populations.

Next question is coming from Jay Olson from Oppenheimer.

We have a question about dose response, which seemed clear in Phase II, but in both of these Phase III studies, the 45 mg and 75 mg doses had similar activity at 12 weeks. So can you talk about any reasons why there was less dose response in these studies? And since most patients should have been in the studies for a while, can you comment on high-level efficacy beyond week 12 and whether or not you saw any dose response after week 12?

Jay, this is Pablo. As Steven described as study design. After week 12, patients in the placebo arm are randomized to 45 mg to 75 mg, and the 45 mg and 75 mg original arms continue to be followed. So we will have additional follow-up going all the way to 54 weeks for safety and efficacy. If you remember from the Phase II study, there was a deepening of the responses we continue dosing in these patients. So when it comes to dose response, we'll have to wait for longer-term follow-up to see if there's a separation of the 45 and 75 we continue follow-up, and we intend to provide updates on that data later in the year.

Our next question is coming from Salveen Richter from Goldman Sachs.

This is Matt on for Salveen. Maybe just kind of going to safety. I realize there was no safety signal observed here. And kind of generally speaking, derms are pretty comfortable using JAKs now in atopic derm. But I was curious if you could speak to anything you're hearing the level of comfort of derms for prescribing a JAK in HS population specifically, just given kind of the high levels of smoking and obesity?

Thanks for your question. This is Jim, Matt. So we're very, very happy to see a very clean safety profile in the 12-week placebo-controlled period. We did not see any AEs of sexual interest related to JAK inhibition. Obviously, we'll have longer-term safety data that we'll share with you at a later point. So in terms of the comfort level that you're speaking about, I do think that dermatologists continue to grow in their comfort in terms of the utilization, the use of JAK inhibitors for their patients. And I think over time, that comfort level will continue to grow. And I think our data will actually add to the comfort level, showing that a very JAK1-specific molecule that we've designed that is -- has high tissue penetration, specifically high skin penetration can provide a very good benefit risk profile. So with that, I mean, we'll provide additional safety information, additional safety data as we get it. But right now, I think our data will provide additional comfort to physicians in terms of their use of JAK inhibitors.

Our next question is coming from Matt Phipps from William Blair.

As the data stands today, I guess, do you see any reason to commercialize both the 45 and 75 mg dose given particularly the similar efficacy in 75 mg have higher levels of acne? And then I realize a bit of a different patient population, but any learnings from the STOP-HS trial that can be used to maybe tweak the Opzelura trials in the more moderate HS population?

So on the first part of the question, I think as I mentioned after a previous question, we'll need to see. We need to see what happens with continued follow-up beyond week 12 on the 45 and 75-milligram doses. And as I mentioned, those are rerandomized. The placebo patients are rerandomized to 75 to 45 mg. So that comparison is going to be pretty meaningful with continued follow-up. So we'll see what the efficacy and safety profile are with continued follow-up. Regarding your second part of the question, we will continue, obviously, we have now this massive amount of data from more than 1,200 patients with HS, and we're obviously going to dig deep into the details to see if there are any learnings that can be applied to the RUX cream studies in HS.

Our next question today is coming from Marc Frahm from TD Cowen.

Maybe just on the idea of the efficacy being a little bit better in the biologic experienced patients. Can you speak to what fraction of the biologic experienced patients have seen IL-17 inhibitors versus just TNF? And does that same pattern of efficacy being a bit better kind of hold in the IL-17 experienced population? Or is it mostly confined to the TNF experienced population?

Certainly, let me have Jim answer that question.

Marc, this is Jim. So we have about almost 40% of the patients that were reported exposure to prior biologics. The majority of them were the TNF alphas, but we also have -- some patients may have been experienced to both the TNF alphas as well as IL-17. We don't have that data. We'll share that when we get that as well as the -- if there's any difference in terms of the response to povorcitinib between those 2 patient populations. But to answer your question, the vast majority of them were TNF alpha exposed.

Your next question is coming from Derek Archila from Wells Fargo.

This question is for Dr. Kirby. I guess do you think the amount of safety data generated so far from povo and HS is sufficient for use in naive patients? I guess, is your view that povo would probably largely used just in experienced patients?

The data that we have suggests use in both patients, and I think it will be used in both bio-naive and bio-experienced.

When you look at the study design, Derek, let's remember, this was the intent-to-treat analysis, which Steven presented showed clear treatment effect across not just the primary, but all secondary endpoints in the entire population intent-to-treat analysis. We think that it's important to highlight the biologically exposed patients because there were 35% to 40% of the study with the stratification criteria. But the bottom line is the study was positive as designed in the entire patient population. And the safety is obviously at this point, we have the 2-week safety data that Steven presented. There were no adverse events of interest and the safety profile, we think it's very clean at this point. In addition to that, as you remember, we have obviously a randomized Phase II data from other studies that shows a consistently good safety profile from povorcitinib.

Next question today is coming from Brian Abrahams from RBC Capital Markets.

Can you remind us of the imputation methodology used in this study for patients who may have discontinued or needed to start antibiotics? How that compares to the other contemporary Phase III HS studies and maybe how that played into the results at all?

Brian, yes, it's Steven. At a high level -- if patients had missing, they were considered nonresponders. Antibiotic use was not allowed pre-study entry. Antibiotic use for HS during the placebo-control period was a nonresponder. Antibiotic use in the very rare instance or a documented infection like a urinary tract or upper respiratory could be allowed. But other -- there's very little to minimal missing data at all, low discontinuation rates. It's a nonresponder imputation method.

Just to add to that, remember, this is the first study that did not allow any concomitant antibiotic use, right? All the other products that are approved all had concomitant antibiotic use. And I think it's important that we took a very strict approach just to look at the monotherapy without any confounding influence by antibiotics on these patients.

Next question today is coming from Eric Schmidt from Cantor Fitzgerald.

Emma on for Eric. Congratulations on the data. One question for Dr. Kirby is, looking at the biologic experienced patients, it looks like the majority of the benefit there in the delta is just coming from a lower placebo response. So curious to hear what your thoughts are on why we see a low placebo response in the biologic experienced patients. And then for the Incyte team, could you share if there were any grade 3 or 4 CPK elevations or thrombocytopenia?

Thank you for your question. With the low placebo rate from the bio experienced group, we are digging into the data to better understand it. This is not a unique signal to our trial but has been seen in some others. So I think as a field really for studying HS and treating it, we need to understand that. So this is an opportunity for us.

Jim, you want to comment on the CK elevations?

Yes, we had -- there were some -- I think there was one patient that had an elevated CK that was grade 3 or 4, but that patient had an intense workout the day before the lab. So both the investigator, we don't believe it was likely related to treatment. But overall, the CPK elevations, the percent was low. I think the main AE that we saw that we believe is related was acne. So that was it from a safety profile. But the CPK elevations, we did not see a worse or significant incidence or severity.

And in thrombocytopenia as well, was that the same?

I'm sorry, I missed that.

Thrombocytopenia or platelet reduction?

No, no. We actually will share that the overall lab hematological profile, but no, we did not see anything worrisome in terms of hematological changes, whether it was anemia, thrombocytopenia or neutropenia.

Our next question is coming from Kelly Shi from Jefferies.

Maybe for Dr. Kirby, would you consider using povo in combination with other biologics given the high unmet need for HS? And also, how do you integrate higher stringent endpoints like HiSCR90 and 100 along with 50 and 75 mg to reassess the overall efficacy profile of povo?

Yes. Thank you for your question. I think our first excitement is really at, number one, having this positive data for the indication of moderate to severe HS. So I think the question of combination therapy will evolve later. It was not a part of this trial design. Second part of the question...

So maybe I'll just address that. So obviously, we are interested in -- and HiSCR75 was a key secondary endpoint. As we showed in our earlier Phase II data at 1 year, our HiSCR100 range was 22% to 29%. So these are endpoints we will look at over time. And as Pablo alluded to, we'll present them when ready, but there will be important efficacy readouts, just not at this juncture.

Your next question today is coming from Kripa Devarakonda from Truist Securities.

I was wondering if you have a sense of percentage of patients who have comorbidities that could preclude a JAK inhibitor, not knowing whether povo is going to get a black box warning or not, safety looks good now -- but in that context. And given what we have seen with the Phase II data, do you have a sense of how long the patient could be on a drug? How comfortable would you keep -- be keeping patient on the drug for?

Well, let me take the first part of the question, and then Dr. Kirby can take the second part. So when it comes to comorbidities, I think that when you look at the demographics that Steven presented, this is a representative population of patients with HS. The BMIs were over 30, the mean BMI and the 30, 32 and almost half the patients, about 40% of the patients were smokers. There were a high percentage of patients with hypertension. So there was clearly -- we didn't select for patients without any comorbidities. This patient population was highly representative of HS. And based on that, the safety data we presented, we think it's very important to keep in mind. Regarding how long patients will stay on therapy? I think the question for Dr. Kirby will be continued -- if there's continued improvement in efficacy as we've seen, I think with the safety profile, one could envision that patients will continue with povo for extended periods of time. But I'll let Dr. Kirby comment on that.

No. Pablo is correct. I think that we're looking forward to seeing what the continued efficacy is as people are on the povorcitinib longer, what those deeper levels of response are in addition to their safety. But keeping in mind, this is a chronic inflammatory condition. In later parts of the study, so we have a long-term extension, Study 312, where some modulation in the dose is allowed. So we'll be looking forward to seeing how these 2 doses perform. And then we also have the ability to give people drug even longer in our 801 study. So we're looking forward to really seeing what that safety database is over multiple years.

And just to clarify, the Study 312 is actually from week 54 to 104. So that's actually an additional year of treatment.

Your next question is coming from Andy Chen from Wolfe Research.

It's another question for Dr. Kirby. If you can take a 5-year view into the future of HS, by which time we most likely have secukinumab biosimilars? My guess is that payers will require adalimumab and secukinumab biosimilars first. So the question is, after these biosimilars, would physicians prioritize potentially a stronger bimekizumab? Or would you try povorcitinib, which is a different mechanism? So I know you mentioned that treatment selection is often aligned with patient preferences, but I don't think patients really think about mechanisms.

Thanks, Andy. I have not been accused of being a fortune teller yet. But I do think that more patients will be put on to biologics in the future. There's better recognition of the disease, better recognition of the burden and the immunomodulatory nature of these biologics. And you're right that people do not always respond sufficiently on that biologic or have contraindications to a biologic. So having another option like povorcitinib is absolutely necessary and important for treatment of this condition.

Next question is coming from James Shin from Deutsche Bank.

One for Dr. Kirby. A lot of emphasis on pain, rapid pain -- addressing the pain. What proportion of patients would opt for safe povorcitinib versus, say, [ Benzonext ]? And then related to the trial, was there -- what was the increase in lipids and cholesterol? Was it in line with JAKs, the previous JAKs?

Let me have Jim first answer the laboratory findings on lipid and cholesterol, and then Dr. Kirby can comment on the first part of your question.

Yes. And we'll have the full safety profile, as I say, as the data comes in, as Pablo mentioned. But no, we have not seen any signals either in this study or in the additional studies that are ongoing or have been run with povorcitinib. So that's not a signal that we've seen.

Related to pain reduction, our approach to the analysis was a 3-point or greater reduction. This is similar to the BIMZELX approach. And I think this is very pertinent for patients and clinicians as this greater reduction in pain is a very important endpoint. So I think that we have taken a very good approach. And I think we have very nice data with a rapid reduction in that greater pain threshold.

I think when you look at the data that Steven presented, what's striking about povorcitinib is the rapid anti-inflammatory effect that it has, and that is reflecting in a rapid improvement in pain. If you look at the slides, we put their week 3 data that there is a substantial improvement in pain in more than 30%, almost 40% of the patients and pain improvement very quickly. That's week 3. We think that is a really important differentiating factor for povorcitinib. And we think it's going to really impact choice of treatment once the drug is on the market.

Your next question today is coming from Evan Seigerman from BMO Capital Markets.

[ Mike ] on for Evan. Looking at the reduction of flares, it looks like both 45-milligram and 75-milligram doses were -- for HS1. Can you talk about how meaningful or not meaningful this is? Could this be a point of that physicians pause on? Or do you think not expect this to be a meaningful detractor.

We think that the reduction in flares as the other endpoints in the study, including HiSCR and the pain reduction we just discussed is critical. I think patients really want the treatment not just that improves and alleviates their symptoms quickly, but that prevents the recurrence of some of this -- the lesion. So we expect that, that's going to be another really important feature of the povorcitinib profile that's going to lead to physician and patients' choice.

Next question is coming from Reni Benjamin from Citizens.

The rapid onset is a standout feature. Can you just quantify how quickly patients saw benefits? Like did they see it even earlier than week 3? And how this differentiates versus, let's say, biologics? And just a related question. In the subgroup of patients that were naive, was that group statistically significant? Or was the positive results for the entire intent to treat really driven by those that were exposed by -- exposed to biologics prior?

Let's have Jim go first, and then Steven will complete.

Yes. So in terms of the onset of action, so we actually saw the patients at week 3. That was the first visit. And so that's why we presented the week 3 data. And so we don't have any data earlier than the week 3 time point. But if you think about it, this is a very highly inflammatory condition and to see something to see pain reduction, we'll share some of the other endpoints like a draining tunnel reduction at a future meeting. But to see an impact so quickly, we're very impressed with, and I think patients will be as well.

And then regarding your question, so just importantly to restate it, the predefined subgroup of interest was the bio-exposed patients, and that's why it was presented that way. That's why it was a stratification factor. And obviously, the implications on the activity are such. The intent to treat overall is active. You could back calculate the bio-naive, and we will supply that data at a future medical meeting, but the drug is active there, obviously, less so because you can see the combined pooled analysis data. But just remind you, again, in the bioexposed, it's an 18% to 19% placebo-adjusted difference, which we think is really important data.

We reached the end of our question-and-answer session. I'd like to turn the floor back over for any further or closing comments.

Thank you all for participating in the call today. We're excited about the opportunity povorcitinib represents, not only in HS as demonstrated by the positive Phase III results, but the entire povorcitinib program. We look forward to sharing updates on the regulatory submissions with you later this year. Before we close the call, I would like to thank our terrific team at Incyte for their commitment to excellence, all the participating investigators and most of all the patients that participated in these studies. Thank you, and have a great day.

Thank you. That does conclude today's teleconference webcast. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.