Incyte Corporation

Greetings, and welcome to the Insight third quarter financial results conference call and webcast. At this time, all participants are in listen-only mode. If anyone should require operator assistance, please press star zero on your telephone keypad. A question and answer session will follow the formal presentation. You may be placed into question queue at any time by pressing star one on your telephone keypad, and we ask that you please ask one question and return to the queue. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Ben Strain, Associate Vice President, Investor Relations. Please go ahead, Ben.

Thank you, Kevin. Good morning, and welcome to Insight's third quarter 2024 earnings conference call. Before we begin, I encourage everyone to go to the Investors section of our website to find the press release, related financial tables, and slides that follow today's discussion. On today's call, I'm joined by Irve, Pablo, Christiana, who will deliver our prepared remarks. Barry, Matteo, and Steven will also be available for Q&A. I would like to point out that we'll be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. I will now hand the call over to Hervé.

Thank you, Ben, and good morning, everyone. The short quarter of 2024 was a very positive quarter for Insight, with a good commercial performance, FDA approval of NIC-TIMVO, and progress of our pipeline with several key data readouts for our clinical programs. In Q3, total revenues increased by 24% year-over-year to $1.1 billion, with net product revenues growing 23%. This growth was driven by the ongoing demand growth for JAKAFI and OBSELORA, which I will highlight in the following slides. In August, we, along with our partners in DAX, announced the FDA approval of Nictimvo for patients with chronic graft-versus-rose disease after failure of two prior lines of therapy, making it the first anti-CSF1R antibody approved to target the inflammation and fibrosis associated with chronic GVHD. To facilitate patient dosing and limit product waste, following the FDA's approval of Nictinvo, we have submitted two smaller vial sizes to the FDA for the approval. Following the potential approval of the new vial sizes, we anticipate launching Nictinvo in the U.S. in the first quarter of 2025. Additionally, the positive pivotal Agave 201 trial results were recently published in the New England Journal of Medicine. NIC-TIMVO was also included in the latest NCCA and clinical practice guidelines in oncology for chronic GVHD treatment, both highlighting the significance of this dataset and the transformative potential of NIC-TIMVO. The SNDA for roxalitinib cream in pediatric atopic dermatitis was recently filed with the FDA, and we are on track for a potential approval in the second half of 2025. During the quarter, we also provided important clinical updates at ESMO with encouraging data for our CDK2 inhibitor in ovarian and endometrial cancers, as well as data from the phase 3 trial of retifamlimab in SCSC. At EADV, we presented extensive data on both povercitinib and roxolitinib cream, including multiple late-breaking presentations that showed the potential of this program to enhance treatment options for individuals with immune-mediated dermatologic conditions such as vitiligo, atopic dermatitis, hydradenitis superativa, and prurigo nodularis. Moving to slide 6, an update of the short-quarter commercial performance of JAKAFI. JAKAFI net product revenue was $741 million, up 16% year-over-year. Paid demand increased 10%, driven by patient growth across all indications. Based on the strength in demand seen during the first three quarters of 2024, we are raising our full year 2024 Jackify net revenue guidance to a new range of $2.74 to $2.77 billion. Turning to slide 7, I'm looking at Jackify's total paid demand by indication during the first nine months of 2022, 2023, and 2024. As you can see, unit growth remains robust. Myelofibrosis is stable year-over-year, with some modest growth seen again this quarter, while the most significant growth is seen in polycythemia vera and graft-versus-roast disease. We expect PV to become the largest contributor for JAK-FI over time, supported by the data from the MAGIC-PV study, which underscores the benefit of early intervention with JAK-FI and its impact on thrombosis-free survivors. Moving to Opsedora on slide 8. Total Opsedora net product revenues in the third quarter were $139 million, up 52% when compared to the same quarter last year. In the U.S., the annual prescription trend for 2022 and 2023 and year-to-date 2024, as shown on the right of the slide 8, reflects continued year-over-year growth of Opsedora from both atopic dermatitis and vitiligo. During the third quarter, we continued to progress with the launch of Obsedura in Europe, so 20 million in net sales during the third quarter were driven by France, where Obsedura is now reimbursed and available in retail pharmacies and from Germany. Earlier this month, we also achieved approval for Atopic Dermatitis and Vitiligo in Canada. On slide 9, I want to highlight three products that are expected to begin contributing to revenue in the near term. We anticipate that Nictimvo for third-line chronic GVHD, Tapacitamab for follicular lymphoma, and Retifanlimab for SEAC could collectively generate 800 million or more in incremental revenues by 2029. We anticipate all three products to be available in 2025, and these incremental sales will be leveraging the current commercial infrastructure used for Monjuvi, Pemazir, and Jaka5. As illustrated on slide 10, these three launches anticipated in 2025 will be followed by larger opportunities in 2026 and 2027, including PovertyNib, CDK2, and Tafacitamab in first-line DLBCF. Between 2027 and 2030, we have multiple programs that hold transformative potential with data for each anticipated in 2025. I will now turn the call over to Pablo.

Thank you, Hervé, and good morning. As we continue to execute on our pipeline of numerous potential first or best-in-class medicines, we remain on track to deliver more than 10 high-impact launches by 2030. In the next few slides, I will highlight a number of these programs. We continue to expand the opportunity of ruxolitinib cream with additional indications. Based on the positive Phase III data in pediatric atopic dermatitis, The supplemental NDA was recently filed. With a potential approval in 2025, we are excited with the possibility of providing an effective non-steroidal topical option for the 2 to 3 million pediatric patients with AD in the U.S. Following interactions with the FDA, we have finalized a design for the Phase III study of ruxolitinib cream in patients with mild to moderate hydroinitis suppurativa. The study, which will have a primary endpoint of high score 75, is expected to begin in the first half of 2025 and could represent a new treatment option to the approximately 150,000 patients with mild to moderate HS in the U.S. As a reminder, we're currently conducting a Phase III study evaluating ruxolitinib cream in patients with prurigo nodularis, a chronic skin disorder that presents as multiple firm nodules commonly located on the extensive surfaces of the extremities and that are intensely pruritic. This pivotal study is enrolling well, and we are now on track to report results in the first half of 2025 with a potential approval as early as 2026. With no topical therapies currently approved for PN and approximately 200,000 patients diagnosed in the U.S., we see this as an important additional option for patients and a significant opportunity for ruxolitinib cream. As shown in slide 15, we're continuing to execute a broad development plan for povercitinib, our oral small molecule highly selective JAK1 inhibitor. Povercitinib is currently being evaluated in phase 3 studies in adrenatus suprativa, vitiligo, and prurigo nodularis, and in randomized phase 2 proof-of-concept studies in asthma and chronic spontaneous urticaria, with data for both expected in 2025. Povercidinib has already shown encouraging efficacy and safety in a randomized Phase II study involving patients with moderate to severe hydranitis suppurativa, a highly painful inflammatory condition. As a reminder, we reported that by Week 52, up to 29% of patients achieved a high score 100 response, indicating complete resolution of all symptoms. Additionally, Povercidinib demonstrated a rapid and significant reduction in pain, offering the opportunity to transform the current standard of care for this disease. The two Phase III studies, Stop HS1 and Stop HS2, are rolling well, thanks to the strong Phase II data and the limited effective treatment options available. We expect to have Phase III data by early 2025. We have refined our guidance for the Phase II proof-of-concept study of povercitinib in chronic spontaneous urticaria and now anticipate data in the first half of 2025. CSU is a mast cell-driven disease characterized by hypes and severe chronic itching. The overactivation of dermal mast cells and basophils leads to increased serum levels of Th1, Th2, and Th17-related cytokines. We know that JAK1 inhibition can modulate mast cell activation, including degranulation and cytokine production, both of which contribute to chronic spontaneous urticaria. This randomized double-blind Phase II study is being conducted in patients who are inadequately controlled or have progressed on second-generation antihistamines, which represent a potential patient population of over 300,000 patients in the U.S. alone. As you can see on slide 16, our updated inflammation autoimmunity pipeline continues to evolve. Recently, we presented promising data from a Phase II study of ruxolinib cream in patients with cutaneous-like implanus. At this time, we do not plan to advance ruxolinia cream into a registrational study for this indication and intend to publish the results of this study in the future. For lichen sclerosus, given the prioritization of other indications and programs, we are not currently planning to advance this indication into a registrational study. As a reminder, 262 and 547 are are currently being evaluated in a number of indications, and we anticipate data for these studies in the first quarter of 2025. Moving to MPNs and Graffitis Host Disease on slide 17. We highlight here a number of ongoing programs where we have the goal of developing new therapeutic options to build upon the significant impact JAK-FI has had on patients. For our BET inhibitor, dose escalation is ongoing, both as monotherapy and in combination with ruxolitinib, As a reminder, we have reported reductions in spleen length and volume, as well as improvements in both symptoms and hemoglobin. We plan to advance this program into Phase III development and expect to provide an update later this year. Additionally, for Xelogaziridib, our ALK2 inhibitor, we plan to provide an update later this year, and for Ruxolitinib XR, we plan to share the bioequivalency data in early 2025. Moving to our oncology pipeline on slide 18. We continue to build a robust portfolio with increased emphasis on first-in-class and our best-in-class and novel immune oncology programs. For tefacitimab, we shared positive top-line results from the Phase III study in patients with follicular lymphoma, and we are on track to file the SNDA with the FDA this year, which could lead to a potential approval in 2025. As a reminder, the Phase III data for first-line DLBCL in combination with R-squared CHOP, is expected in the first half of 2025. During the ESMO conference in September, we shared positive top-line results for the pivotal Phase III study of retifanilimab in SCAC. Retifanilimab met the primary endpoint, demonstrating a clinically meaningful 37% reduction in the risk of progression or death with a hazard ratio of 0.63. The study showed that retifanilimab was generally well-tolerated, and no new safety signals were detected. At ESMO, we also shared promising evidence of clinical activity from our potentially first-in-class small molecule CDK2 inhibitor, which demonstrated a number of complete and partial responses, as well as stable disease in patients with cyclin E1 overexpressing tumors, most notably in ovarian and endometrial cancer. We believe our CDK2 inhibitor could be a foundational therapy for patients with ovarian cancer, as well as other cyclin E1 overexpressing tumor types, and we plan to move aggressively in initiating registrational studies in 2025. We will be meeting with FDA in the coming months to discuss trial designs. As highlighted on the slide, we're considering different designs for the registrational program, and we will continue to update you on the regulatory strategy for this program in the coming months. In closing, Slide 20 shows a summary of the considerable number of milestones across the remainder of 2024 and 2025. These milestones will continue the transformation of our pipeline with a strong focus on new molecular entities with the potential to make an indelible impact on patients. With that, I would like to turn the call over to Christiana for the financial update.

Thank you, Pablo, and good morning, everyone. Our third quarter results reflect strong commercial execution and continued growth with total revenues of $1.14 billion up 24% versus the same period last year. Total product revenues of $963 million in Q3 were driven by strong demand growth for Jakafai and Opsilura and increased revenue contribution from Monjuvi as a result of the acquisition of hood rights to Tafasitamab earlier this year. Total royalty revenues were $157 million, up 20%, compared to the third quarter of 2023, driven by increased demand for Jacovi and Olumient. Turning to Jacopi on slide 24, Jacopi net product revenues were $741 million for the third quarter, reflecting continued demand growth, with total demand up 10% year over year, driven by growth in all indications, and a $9 million gross to net favorability as a result of two ups to prior quarter estimates. At the end of Q3, channel inventory was up 2% year-over-year and stable quarter-over-quarter and within normal range. Turning now to Obsolura on slide 25, net product revenues for the third quarter were $139 million, representing a 52% year-over-year increase driven by growth in new patient starts and refills across both AD and vitiligo in the U.S., as well as continued contribution from the commercialization of Opsalura for vitiligo in Europe. In the third quarter, Europe contributed $20 million of Opsalura net product revenues, driven by continued uptake in Germany and broader access in France, where Opsalura is now reimbursed and available in retail pharmacies. Third quarter net product revenues in France include a $2 million stock built up at wholesalers. Finally, in the third quarter, we made significant progress in including Opsalura on regional formularies in Spain and Italy. Moving on to slide 26 and our operating expenses, total GAAP R&D expenses were $573 million for the third quarter. due to the $100 million milestone payment made to Microgenics during the quarter, and continued investment in our late-stage development assets. Excluding all one-time expenses, ongoing R&D expenses for the third quarter increased 26% compared to the same period in 2023, due to continued investment in our late-stage development assets, additional R&D expenses resulting from the Asian acquisition, and timing of certain expenses. For the nine months ended September 30, 2024, ongoing R&D expenses increased 15% compared to the prior year period as a result of increased investment in the Phase III studies of povocitinib and Opsalura. As we wrap up the clinical development of axatilimab in third-line chronic GVHD, tafacitimab in relapsed refractory follicular lymphoma, and retifamilimab in SEAC and non-small cell lung cancer, as well as the development activities of discontinued programs, we anticipate the reduction in investment in those programs to partially offset the increased investment in other programs, which would allow us to control future R&D expense growth. Moving to SG&A, total GAAP SG&A expenses were $309 million for the third quarter, representing a 15% year-over-year increase primarily driven by timing of consumer marketing activities and certain other expenses. For the nine months ended September 30th, total GAAP SG&A expenses increased 6% year-over-year. Finally, total ongoing operating expenses for the first nine months of the year increased 11% versus a 14% increase in revenues, leading to an increase in operating leverage and margin. Moving on to our guidance for 2024, based on the strong performance of JAK-FI in the first nine months of the year, we're increasing our full-year 2024 guidance to a new range of $2.74 to $2.77 billion. We're also updating our full-year guidance for other hematology oncology products to a new range of $310 to $320 million to reflect the first nine months' actual demand and the unfavorable impact of foreign exchange rates. In addition, we are updating the full-year gap R&D guidance to include the $100 million milestone payment to macrogenics. The full-year gap R&D guidance is now $2.54 to $2.59 billion, which includes $791 million in one-time expenses related to the $691 million of upfront consideration for the acquisition of Asian and the $100 million milestone payment to macrogenics. Ongoing R&D guidance remains unchanged. Finally, we are reiterating our full year 2024 guidance for COGS and SG&A. Operator, that concludes our prepared remarks. Please give your instructions and open the call to Q&A.

Certainly. We'll now be conducting a question and answer session. As a reminder, we ask you please ask one question, then return to the queue. If you'd like to be placed into question queue, please press star 1 on your telephone keypad. One moment, please, while we poll for questions. Our first question today is coming from Michael Schmidt from Guggenheim. Your line is now live.

Hey, guys. Good morning. Congrats on a great third quarter, and thanks for taking my question. I had one on poversitinib. Just looking ahead to the upcoming Phase III data in hydrogenitis early next year, the Beyond top-line success, do you have any thoughts on where you think, where you want efficacy to shake out in order to be competitive with Humira and other marketed biologics? Is there a particular placebo-adjusted effect size that you're looking for to hit with the coercive test? Thanks.

Michael, it's Stephen, just taking your question, and thank you for the question on HS. You know, our feeling is if we replicate the Phase II data, which was incredibly strong, and as Pablo said in his prepared remarks, that includes a Hiscar 100 of up to 29 percent, then we'll have an extremely favorable efficacy profile that will really benefit patients with HS. You couple that with, you know, the other symptomatology, particularly the pains, from the lesions, and we were able to get in that phase two data set to demonstrate pain relief, and that will add to what we think will be a differentiated profile that will really benefit patients. Obviously, it's hard to predict how phase three will read out. The other thing Pablo alluded to in his prepared remarks is the extremely good enrollment on both studies, which is probably a testament to the phase two data drive in investigators wanting to put patients on the study. Thanks.

Thank you. Next question is coming from Jessica Five from JP Morgan.

Your line is now live.

Hey there. Good morning. Thanks for taking my questions. I had a few on the pipeline. I believe earlier this morning Novartis announced that longer follow-up time is needed to determine the regulatory path forward for their bet inhibitor. Curious how that impacts at all your thinking or development strategy for your bet. And then Can you help us think about the potential development plans for poversitinib and 262 in CSU, and just kind of where you see both molecules best fitting in the treatment paradigm? Thank you.

Yes, good morning, Jess. This is Pablo.

Let me take the first one. So our BET inhibitor, as we've presented over the past year, and we will provide an update later this year, We're very happy with the data that we've seen so far. We've seen spleen reduction, spleen volume reduction. We've seen a pretty impressive improvement in symptoms, obviously with the caveats that this is not randomized blinded data, but very important effect on symptoms. We believe that the ability of our PET inhibitor to be dosed continuously as opposed to the way Pelabrasiv has to be dosed with a break of a week every two weeks could potentially make an important difference in our ability to control symptoms. Our plan remains the same, as I said in my prepared remarks. We'll provide an update on the data before the end of the year, and we intend to advance into a phase three study, and we will provide details on those designs when we provide an update on the data. So that plan remains the same. On POL 1262 for CSU, both are in different stages in a way. POL, as you know, is in a randomized phase two study with proof of concept. We believe there's a potential for POVA in this indication because of the very strong anti-inflammatory effect that it has. So we look forward to sharing data and future plans after that. 262 is in a randomized phase two study with two dose levels at 50 and 150 compared with placebo. And we also initiated a study or a lower dose of 25 milligrams compared with placebo. And the idea here is to explore a full range of doses for 262 to potentially, once we have the results, assuming positive results, to be ready for pivotal studies. In terms of how both fit, you know, I think the difference here is probably a sequence on how these medicines could potentially be used in patients with CSU. As you know, first line of therapy is antihistamines. About 50 to 60 percent of the patients do not respond to antihistamines or progress on antihistamines. This is a multi-year disease, and so patients need a sequence of treatments to be used to see which one controls best the symptoms for that particular individual. The mechanism is different. Poverty syndrome has a broad inflammatory effect. 262 is exquisitely designed to block, you know, MRGPRX2 in mast cells in the skin. So we believe that that selectivity will lead to an excellent safety profile. So once we have data for both programs, we'll share a little bit more how we think those can potentially be sequenced in the treatment paradigm. Thank you.

Next question today is coming from Salveen Richter from Goldman Sachs. Your line is now live.

Good morning. Thank you for taking my questions. Just regarding the SGM portfolio, could you just help us understand how you're thinking about development strategy here when you think about the different mechanisms addressing some of these diseases and how you see the differentiation playing out? Thank you.

Yeah. So we have two programs that were acquired with Essient, MRGPRX2 and MRGPRX4. So MRGPRX2 is currently being developed in three indications, chronic spontaneous urticaria, and I just highlighted where we are with that indication. We have an ongoing study with two dose levels versus placebo, 50 and 150, and a second study of 25 milligrams versus placebo. Once we have all that data, we'll decide next steps for chronic spontaneous urticaria. For the other two indications are chronic inducible urticaria, particularly focused on two of those, demographism and cold-inducer urticaria and atopic dermatitis. The reason why we like the MRGPRX2 as a target is the excellent selectivity, not just for a cell type, mast cells, but also mast cells specifically in the skin and connective tissues. And we think that should lead to an excellent safety profile and make this, perhaps, in some of these patients, the first therapy after patients progress on antihistamines in the case of chronic urticaria, for example. So good evidence of efficacy together with very, very clean safety, we think it will make this a very important option for patients at that stage of the disease. The second program was MRGPRX4. This has been developed in patients with cholestatic pruritus, specifically primary biliary cirrhosis and primary sclerosing cholangitis. We know that X4 is a receptor. Bile acids and bile salts bind to it, and this is an important way in why this patient is having tractable pruritus. We are conducting a randomized double-blind study, and those indications will have date in the first quarter of 2025, same as for MRGPRX2 program. And once we report all the data early next year, we'll give you clarity on the next steps.

Thank you.

Next question is coming from Eric Schmidt from Cancer Fitzgerald. Your line is now live.

Well, thanks for taking my question, and congrats again on all the updates. Maybe a commercial question for Matteo on Upsalura and the potential upcoming launch for pediatric AD in the second half of next year. How do you think you're doing with regard to formulary access and efforts to ensure reimbursement in what could be a pretty sizable marketplace? Next.

Yes. Thanks, Eric, for the question. On the pediatric side, we're very excited about the potential for us to bring this new tool to patients 2 and 11 years old in AD. The unmet need is very clearly there. We have 2 million patients. In terms of sizing, they're still cycling vastly on TCS and TCIs, and they still remain a high need for us to potentially get into that. In terms of the 2025 formula coverage, I mean, we look at the formula position for the entire Obsolura brand for next year. Right now, from the feedback that we're receiving, we're confident that we will have a competitive overall coverage also for next year, and that will include, obviously, the pediatric indication if it had to come to fruition.

Thank you. Next question is coming from Kelly Shee from Jeffrey's. Your line is now live.

Thanks for taking my question. I was curious for the phase 3 trial of COVID. ruxolitin, ibuprofen in the mild to moderate HS. What is the rationale for using most stringent primary anapole in a high score of 75 over typically used high score of 50? Thank you.

Yeah, Kelly, it's Stephen. Thanks for the question. So firstly, you know, there's a lot of unmet need in mild to moderate HS. Defined in our study as people with abscess and nodules of a count of about 3 to 10, no draining tunnels. And those patients can have a reasonable placebo effect because of the disease phenotype I just described to you. So that's looking at Hiscos 75 will help to control for that. It's a higher endpoint, a higher bar. Obviously, you know, address the unmet need and hopefully, you know, eliminate a large placebo effect to get it across the finish line. It's agreed with regulatory agencies, and we're a go on the program. Thanks.

Thank you. Next question today is coming from Matt Phipps from William Blair. Your line is now live.

Good morning. Thanks for taking my questions in the next quarter. I had another question on 262. The clinical trial recently showed the addition of a 25-mig arm to that CSU trial. Can you give us any rationale for that? I assume that is maybe not going to be included in the Q1 update, and also just thinking about the profile here, are you guys, should we think most about, I guess, competing with the recent BTK data as far as another oral, or do you look at maybe some of the more effective treatments like the KID inhibitors as far as I can see goes?

Yes, Matt, thank you for the question. So the reason for the 25 is to have, to explore the full range of doses. So as you point out, there's an ongoing study, 50 versus 150 versus placebo. That's the data that we're going to have in the first quarter of 2025. We decided in the meantime to start a second study with 25 milligrams versus placebo in order to have the full range of doses explored. So if we have positive data in the ongoing study, then we'll be ready with the 25 already running to get to a phase three study faster. So that's the idea of the 25 milligram, to explore the full range of doses 262 in patients with CSU. In terms of where it fits, you know, I mentioned a few times before that we don't necessarily expect to send the same level of efficacy that you may have with a KIT antibody. When you deplete all mast cells, which is what KIT antibodies do, obviously the efficacy is very strong. In our opinion, that comes with a series of side effects that have been well reported. I think with BTK inhibitors, a little bit cleaner in terms of safety profile. We think 262... if it shows positive data in CSU, will fit perfectly after antihistamines. Once patients progress on antihistamines, what we expect to be a very clean safety profile for a very convenient daily pill will be ideal for those patients before they need to try more aggressive alternatives. So that we continue to believe is a perfect fit for 262 in CSU.

Thank you. Next question today is coming from James Shin from Deutsche Bank, your line is now live.

Hi, thanks for taking our question.

For Ruxolitinib creams HS phase three, what time point is the high score 75 being assessed? When I look at the pipeline slide, it shows the approval range starting around mid-27 timeframe.

So is phase three HS data for RuxCream expected in 26?

It should.

Yeah, Stephen, it's hard to be given much precision beyond what we showed in that for the moment because of, you know, the study has to start and be underway and then see how it enrolls. The endpoint is his score, 75, as agreed with regulatory agencies. And, you know, we'll update at a more appropriate time and try to give more precision on the endpoint. We expect, given the unmet need, the lack of competition in the space and the excitement around this that it should enroll well, but we'll see how it goes at a later time. Thanks.

Thank you. Next question today is coming from Vikram Purit from Morgan Stanley. Your line is now live.

Hi, good morning. Thank you for taking our question. So we had one on the oncology pipeline. For the Phase I data sets expected for the mutant CalR program and then also for the JAK2V617 programs in 2025, Could you help us understand just the scope of those data releases that we could expect to see and how you'll be gauging success for these initial data sets? And if I could squeeze a question in on the base business, for Abzalera, could you just give us a sense of how utilization is tracking in terms of tubes per patient per year for both AD and vitiligo versus your last update?

Thank you. Let me take the first one on the pipeline. The mutant cholera antibody program is ahead of 617F. As we discussed previously, a 617F program this year started in healthy volunteers to understand the formulation better, and then we advanced it into in myofibrosis patients, and it's now in patients, but it's a little bit behind mutant cholera antibody. We expect both to have meaningful data available next year, but that data will be comprised of basically a fairly large number of patients with single agent, particularly for the mutant color antibody, and some of the data also in combination. I think it's difficult to start putting numbers around what success looks like. What we've been consistent about is that what we expect to see, in addition to obviously addressing some of the signs and symptoms of myeloproliferative neoplasms, is to see some evidence of decrease in VAF or allele reduction with these medicines. And we expect that we will have that data next year when we decide the right timing to disclose to provide an update.

On obsoluta utilization, for AD, we still see over two tubes per patient per year. For vitiligo, we're beefing up the cohort that we're following throughout the time to make sure that the cohort is meaningful enough and as well as we follow long enough to have a very reliable number What you see on the prescription side is that the growth rate is actually coming from new patients as well as refills, so we continue to improve over time. At the same time, we're increasing the focus on the overall adherence, and we have quite exciting programs kicking off this quarter and the first quarter of next year to actually put more emphasis on this part of support for our patient population.

Thank you. Next question today is coming from Derek Archilla from Wells Fargo. Your line is now live.

Hey, good morning and congrats on the quarter. Just two quick ones. Just on 262, I just want to know if you've characterized the trip taste reduction you've seen with the agent in the earlier stage trials. And then just on the base business, just in terms of what we've seen with Jackify and the MF market, it looks like you're still driving new patient volumes. Just was wondering if that's more share gains or just the overall market growing. Thanks.

Let me take the first one on 262. So we are measuring tryptase in the ongoing trials. A word of caution, I think that the degree of the magnitude of tryptase reduction that we expect to see is not the same you'll see with depletion of mast cells by using the KIT antibody. I mean, it's just common sense that if you deplete mast cells regardless of their location, you're going to have, particularly those in circulation, you're going to have pretty dramatic decrease in tryptase in circulation. What we address with 262 is MRGPRX2 in the mast cells in the skin, as a result of which the decrease in tryptase that we may see, it's not going to be quite as dramatic. But we are measuring that, and we will report it.

Thanks, Derek. Yeah, as far as myofibrosis market goes, JAKIFI, as we said, continues to grow. Total patients increased 4% in myofibrosis. But in fact, yes, the overall market is growing. Patients are getting first line. They're starting earlier because now you have multiple agents to go to after Jackify, and patients are being treated in the second line, third line, and even fourth line setting, which we had not seen before.

Thank you. Our next question today is coming from David Lebowitz from the Citi Banker line. He's now live.

Thank you for taking my question. Just following up on the Jackify question, I understand that the step down in the catastrophic out-of-profit costs are in the middle. They'll be at their lowest at $2,000 per year next year. Has that played any role in the uptick in Jackify growth in the current quarter? And then looking forward to later in the year, could you outline what type of data we might actually see at ASHE?

So I'll take the first question and hand it over to Stephen or Pablo. So, yeah, so Jackify, well, what we always believe that Medicare Part D patients who are cancer patients out of pockets should really not be a barrier to use. So getting rid of the catastrophic coverage this year for patients on Medicare Part D was a very good thing. Going to $2,000 out-of-pocket next year is a very good thing, and especially smoothing over the whole period of time, so patients out-of-pocket at any given month is better. But really, the growth that we see is coming from demand, and mostly, as we've said, from polycythemia vera, and mostly that's because physicians are starting patients earlier on JAKIFY and polycythemia vera because of the results largely from MAGIC-PV, which demonstrates that patients will have thrombosis-free survival improvements when they start JAK-FI and when they start JAK-FI earlier.

Stephen? David, it's Stephen. Unfortunately, it's premature to comment on what will be seen at ASH. We have to wait for the acceptances, and then we'll provide the update at that point.

Thank you.

Next question is coming from Mark Fromm from TD Cal. Your line is now live.

Hi, yes, thanks for taking my questions. Just on 262, back to adding the 25 milligram dose, can you just talk about kind of what led to adding that, and was it informed at all by the AD trial, which I believe is marked as completed as of over the summer? And then just when you get the data from those different dose levels in CSU, obviously you don't necessarily need to match the kit antibodies from an efficacy perspective given the potential for improved safety here. But what is that kind of minimum bar that would justify use of a branded drug, you know, after antihistamines in your mind?

Yeah, so let me, first of all, the decision to start, whether it's indeed a new study or it's part of the ongoing study, but it really is a totally separate cohort with 25 milligrams versus placebo, they had nothing to do with any data that we've seen from the program. We made that decision early in the process, very soon after the transaction closed, and it was based on our desire to be ready for a phase three study as soon as possible once we have data. That decision was made at that time. In terms of the bar, look, all the patients in the ongoing study are refractory to antihistamines. So basically after that, the question is, what's the best option for this patient? We believe in that context, obviously showing efficacy over placebo and with what we believe will be an excellent safety profile will be sufficient for 262 to be the first option after antihistamines in some of the patients with CSU. We remain convinced that that is the right place for this drug to be used, assuming obviously efficacy in the randomized trial.

Thank you.

Next question is coming from Brian Abrams from RBC Capital Markets. Your line is now live.

Hey, good morning. Thanks for taking my question, and congrats on the quarter and all the progress. Maybe on the CDK2, I'm curious if there's any updates on the aspects that you're considering as you think about the next steps and pivotal plans into the upcoming FDA meeting and sort of, you know, how you're thinking about the balance between exploring late line versus maintenance. And then any more color around the companion diagnostic for that drug. Thanks.

Yeah, Brian, it's Stephen. Thanks for the question. So, you know, as Pablo said in these slides, there are numerous areas we're interested in, but broadly speaking, the ovarian cancer settings divided into a platinum refractory and a platinum sensitive setting, you know, divided by a time period of approximately six months, although that's getting gray in terms of retreatment. And there are different unmet needs in each population, and we're interested in both. You know, you saw the data update at ESMO. You know, we got upwards of north of a 30% response rate, but the data is still maturing, and there may actually be late responders where it may go up. So we really like the profile we've seen. We've done 200-plus patients of dose range in work, so we think we're in a very good place to pick both a dose and schedule. In the platinum refractory ovarian cancer setting, there are potentially two ways of thinking about it. For the U.S., primarily the FDA, one could do a single-arm study in that setting, looking at response rate and durability of response to get it across the finish line. As potential confirmatory study and for ex-US approvals, it will require a randomized study in that setting. And as was on the slide deck, that would be against investigator-choice chemotherapy, of which there are numbers. There's single-agent paclitaxel, topotecan, liposomal doxorubicin, et cetera, with a time-to-event endpoint like progression-free survival. And we like the profile of the drug there. The other setting that's of extreme interest to us, and we spoke about it at ESMO quite a lot, is the platinum-sensitive ovarian cancer setting, particularly where bevacetamab maintenance is used. And the disease gets a little complicated there because you look at HRD-proficient and HR-deficient patients in terms of use of PARP inhibitors. But if you just focus on the majority population there, The HR deficient patients, you know, the majority of those are cycling E1 positive. We're doing safety work now with CDK2 and BEV maintenance, and that's an enormous interest to us. There's need there. We can potentially improve cure rates, and it would be a pretty simple construct in terms of design. It will be BEV maintenance plus placebo versus BEV maintenance plus CDK2, and we're doing the enabling work for that now. That is obviously a longer study and will deliver later, but we like the profile of the drug there that we've seen so far in terms of its therapeutic ratio. So those are the areas of interest in terms of study designs. On the companion diagnostic, we haven't given details per se on what our cutoff is, but there's two ways of looking again at this population. You can look at the gene in terms of amplification, the CCNE1 gene, and others are doing that, Or you can look at protein overexpression by IHC, cyclin E1 expression, and that's where we focused. And that is a much bigger population. With our cutoff, it's probably more than half of ovarian cancer right now. But we need to have more discussions with regulators and CDH on our companion diagnostic and the cutoff we're using. But the data we showed at ESMO was using our assay with the cutoff that we've determined internally. Thanks. Thanks.

Thank you.

Next question is coming from Andrew Berens from Leerank Partners. Your line is now live.

Hi, this is Emily Shuttman. I'm for Andy. So with the upcoming HS readout for POBO, just one question looking ahead to the commercial dynamics. So the efficacy looks strong relative to other agents being developed for HS, even though it's oral. I was wondering how you see the safety of POBO and if the JAK class concerns are reflected on the label, how might that impact the drug commercially? I guess I'm asking if you anticipate a black box like other JAK agents. Thanks.

Yes, Stephen, I'll address that. I mean, we've spoken a bit about, you know, how well the studies are going. The Phase 2 profile we saw with the Hisco 100 upwards of 29%, and, in fact, enrollment is going very well. You know, it is an inflammatory disease, so there is a reasonable chance or more than a reasonable chance that it will have class effect labeling in terms of a black box. So we do expect that to be the case going forward. If you look at the profile of a JAK-STAT inhibitor versus a biologic, which will only attack, by definition, one pathway, for example, IL-17, here we can have more broad coverage of different interleukins, and then potentially that would result in better disease control, as we saw in the Phase II data. And that's the data set we'd like to replicate.

Thanks. Thank you. Our next question is coming from Andy Chen from Wolf Research Reliance. Is that live?

Hey, good morning. Thank you for taking the question. I'm curious if you can remind us the size of your sales force and how it's split across Heme and Derm and others. I'm trying to figure out if your SG&A would trend up as you get your topical into pediatric AD, into PN, and also your JAK inhibitor. Are you going to double down on the Derm sales force, or are you going to capitalize on existing synergies? Thank you.

So I guess in the U.S., Madeo can speak about that. I mean, the big picture is that we have established around the world, in fact, now in most of the European countries, in the U.S. and in Canada, we have dermatology, IAI teams that are in place and are sized in a way where we anticipate that they will be able to do research Most of the work required for the launches of the new indication, absolutely clearly for Opsalura. And when Povo comes up, it may be marginal increase, but nothing that is very high. I mean, how many people do you have now in the U.S., Matteo?

The full footprint across all teams is around a couple of hundred people. We see it in line with other competitors. We also saw competitors staffing up a full field force dedicated to H.S., We look forward to see the Phase III data next year, but from what it looks like now, it's going to be a mix of exactly staffing appropriately while capturing synergy with the current footprint we have.

Thank you. Next question is coming from Jay Olson from Oppenheimer. Your line is now live.

Oh, hey. Congrats on the quarter, and thank you for taking the question. Since you have a number of catalysts in the near term that could reshape the future top-line growth, Can you talk about which one or two catalysts are most important, and are there any gaps in your portfolio, and how are you thinking about business development strategy over the next year? Thank you.

Yeah, maybe I'll take that. I mean, so if you go to the slide that we just presented, the slide 10, and it's basically saying what has happened recently is the deprobarization or the increase in probability of success for Taffer. Nick Timbo is approved in third line. and retifonlimab in SCSE. And as I said in my presentation, we collectively, if you put them together, you end up with something that would be around 800 million. So each of them are relatively modest, if you want to classify them. But when you put them together, this is the meaningful contribution to the top line by 2030. What we have coming soon is POVO, CDK2, roxalitinib, EXAR, and tafacitamab in first-line DLBCL. So that's Again, the number of projects that have been where the probability of success has increased with recent events. I mean, for CDK2, clearly the data is good. For povercitinib, you know, the Phase II data that we have accumulated is showing very good level of efficacy. And in fact, the follicular lymphoma data for TAFA, which is the first of the CD19-CD20 combination, is in some way... improving our chances of success in the first line setting where we are also doing CD19, CD20 combinations. So that's the second step. And then we go into MKLR, X2, 617F, TGF, Beta, PD1, all the early pipelines that is moving very well. So what it does to us in terms of business development is really looking at maybe early technology type of deals where there are always things we can acquire, learn from, that we would be interested in, or in the very hypothetical situation where we would find some of that, some very late stage, like commercial product that would be also of quality that we would ask for, which is not very common in oncology and dermatology, and are very expensive. So in some way, you know, we are in a position today where Our internal pipeline plus the acquisitions that we have done or the BD we have done recently is giving us a portfolio that works very well for what we need to compensate the Jackify patent expiration around 2029. And we are not looking in the very short term at acquiring new assets that would require a lot of R&D expenses. And that's why we look at either early or very late with contribution to the top line that will come very quickly.

Thank you. Next question is coming from Kevin Clark Gardner from Evercore ISI. Your line is now live.

Hey, guys. Thanks for taking the question. Also had one on 262 in CSU. I'm just wondering how many patients are ZOLAR-naive versus experienced in the study, and if you think there could be any potential subgroups with greater efficacy, such as IgE-low patients. Thank you.

So thank you for the question. So we're not going to provide any details on prior therapy in the study other than to say that all patients have refractory to antihistamines. In terms of the potential for certain subsets to have better efficacy, I'd rather not speculate at this point in time. Obviously, it's a very different mechanism for Zolair, which is, as you know, an anti-GE Anybody as opposed to 262, they're working a different pathway. But I'd rather not speculate at this point about the results, the future results of the study.

Thank you. Next question is coming from Evan Siegerman from BMO Capital Markets. Your line is now live.

Hi, guys. Thank you so much for taking my question. I'm just thinking about the ALF program readout in 4Q. I know you don't want to speculate too much, but maybe comment on kind of your confidence in this readout. Just like this program has a few ups and downs despite the mechanistic rationale, and maybe highlight what gives you the confidence in the update and really in the program overall going forward. Thank you.

Yeah, Evan and Stephen. You know, as we've been alluding to over the last year, we've sort of had to go to higher and higher doses to try and achieve the desired effect of the program, which, just to remind you, would work potentially through inhibiting hepcidin and then relieving that break so that iron gets released and patients' hemoglobin improves from the underlying disease and then potentially from drug-induced disease. And I think it's safe to say at this point in time, you know, we haven't seen to date yet sufficient efficacy to trigger a go on a future registration program. We'll update more data at the end of the year at an appropriate meeting and give you more color on that. Just to remind you, though, we do have an ongoing program in FOP that continues to enroll with ELK2. Thanks.

Thank you. Next question is coming from Tasneem Ahmad from Bank of America. Your line is now live.

Hi. Thanks for taking my question. As you think about the HS opportunity, can you clarify for us how you think it would be different for RuxCream versus POVO? And also, do you have a sense, I know it's still a little bit early, but in terms of usage of tubes for RuxCream and HS, how do you think that will compare relative to what you have seen so far for AD and vitiligo? Thanks.

So, Stephen, on your first question, so there's a spectrum of disease that goes, you know, mild, moderate, and severe in HS. They're called Hurley stages, classifications by the number of abscesses and nodules, the number of draining tunnels and fistulas. Just to address the mild to moderate for which the cream is targeted in, As I said earlier, the abscess nodule count there is limited to less than 10. To get on to our particular study, you have to have 3 to 10 abscess nodule count. There are no draining tunnels or fistulas in the mild to moderate population. And the Hiscar 75 will be the endpoint. And they're approximately up to between 100 and 150,000 patients with this with a lot of unmet need. These patients tend to be underdiagnosed in the setting and tend to have disease for a long time before getting appropriately diagnosed and seeking treatment, and it may need chronic treatment. It's hard to determine now until we conduct the study and get the readouts to exactly how long that would be. In terms of povacitinib, it's looking at the right spectrum of the disease, so the moderate severe population with higher abscess nodule counts with the presence of fistulas and draining tunnels, and then the endpoints can go towards potentially As Pablo said in his prepared remarks, complete resolution of everything, abscess and nodules and removal of the draining tunnels and fistulas, which will be called a HISCAR 100, obviously, you know, addresses a huge unmet need and takes care of a lot of morbidity. And again, you know, chronicity of treatment and how many tubes will be needed will come, you know, from the phase three study readout, but it'll tend to be long therapy if you want to just ballpark it at the moment.

Thanks. Thank you.

Next question is coming from from Truist Securities. Your line is now live.

Hey, guys. Thank you so much for taking my question, and congrats on the quarter. I have a question about the CDK2 program. I know some of the questions were already answered, but one of your peers just announced a discontinuation of their CDK2 program. I was wondering if you can help us understand how you see the competitive landscape given your data. And before you have the conversation with the FDA or before you move into pivotal trials, should we expect to see any additional data from either ovarian cancer or any of the other indications that you're investigating the drug in? Thank you.

Let me take that question. So in terms of competitive landscape, The competitive landscape for CDK2 is a little bit beyond the mechanism, right? I mean, we think when it comes to ovarian cancer, we are ahead in terms of developing a CDK2 program. We disclose the data, as you know. We have over 200 patients treated. We explore a range of doses. We're seeing clear evidence of efficacy and a very, very manageable safety profile. So we intend to start registrational studies next year, which I think that puts us in front when it comes to CDK2 inhibition in ovarian cancer, and perhaps also in endometrial cancer. We're doing additional work in other indications. Now, the competitive landscape is a little bit more complicated than just CDK2 because there's a number of ADCs being developed in ovarian cancer. Obviously, mirvituximab is approved for certain patients with followed receptor alpha expression. There are other ADCs, the same target, as well as additional targets for ADCs. I think that the two points I would make is, number one, there isn't complete overlap when it comes to populations, at least not with receptor-alpha positive patients. Perhaps for some of the others, the overlap will be a bit more pronounced. But one of the reasons why we believe the maintenance study in combination with Bevacizumab is very important for us in the long run is because that might be the perfect setting for an oral, convenient, well-tolerated molecules such as our CDK2 inhibitor. So while we intend to move aggressively into platinum-resistant patients to get a fast-to-market strategy there, we believe that maintenance will differentiate our CDK2 program not only from other entrants in the same target, but also against ADCs.

Thank you. Our final question today is coming from Ren Benjamin from J&P Securities.

Your line is now live.

Hey, thanks, guys, for squeezing me in, and congrats on the quarter. I guess just, you know, when we think about the potential for positive Phase III data from STOP, HS1, and HS2, do you need even like longer-term follow-up data, or do you feel that you can file kind of right away? And assuming an approval in 2026, how do you see this being used, you know, in relation to, you know, currently approved therapies, and what kind of market share do you think you might ultimately achieve? I know Stephen has talked about greater than 300,000 patients, but how many patients do you think you might be able to treat?

So, Ren and Stephen, I'll at least do the first part to your question. And obviously, we can't speak about a lot of the regulatory aspects, but it is an NDA, a first filing, so there'll be safety data that'll be needed and we'll provide updates at the appropriate time. But we continue to guide to a 2026 approval for that at the time. In terms of, you know, it will be really up to what you see ultimately in terms of the efficacy profile vis-a-vis other orals or biologics in terms of use. There are a lot of patients with the disease, a lot of unmet need, and there'll be a lot of cycling through therapy. I think the numbers we give is between 150,000 to 300,000 patients with this moderate to severe in total, you know, in terms of seeking therapy potentially. And then, you know, use of biologics versus orals, et cetera, will depend on the the profiles of the drugs from the phase three setting. Thanks.

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

Thank you all for participating in the call today and your questions. The IR team will be available for the rest of the day for follow-up. Thank you and goodbye.

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