INCY - NASDAQ

Greetings, and welcome to the Incyte Second Quarter 2025 Earnings Conference Call and Webcast. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Greg Shertzer, Senior Director of Investor Relations. Please go ahead.

Thank you, Kevin. Good morning, and welcome to Incyte's Second Quarter 2025 Earnings Conference Call. Before we begin, I'd 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 am joined by Bill, Christiana and Pablo, who will deliver our prepared remarks. Matteo, Mohamed and Steven will also be available for the Q&A. I would like to point out that we will 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 Bill.

Thanks, Greg, and good morning, everyone. Before I get started and on behalf of the Incyte management team and the employees, I'd like to thank and recognize Herve Hoppenot for his leadership and commitment to Incyte over 10 years. His contributions to this company were invaluable and greatly appreciated, and we wish him the best in his retirement. As you know, I started at Incyte very recently, roughly 30 days ago. And so before jumping into the quarterly results, I'd like to touch on 2 fundamental questions I've been asked since joining Incyte. The first one is, what specifically attracted me to the company. And second, what are my initial thoughts on strategic priorities. In response to the first question, I naturally studied the company and the business in great detail and spoke to many different stakeholders, including physicians, patients and investors before joining. And my initial impression is that Incyte has all the intrinsic characteristics of a high-quality growth business. That is the potential for new meaningful product flow, attractive markets, R&D and commercial capabilities and a strong balance sheet. I believe there's a foundation in place and a path to value creation, but time is of the essence. The nontrivial challenge Incyte faces is navigating the company through 2029 and transitioning to a new set of durable product growth drivers. On the potential for meaningful new product flow, Incyte has several important product launches between now and 2030. These products, of course, will vary in size. Some will contribute substantially and others incrementally to growth. But either way, there is substrate here. Marketed products Opzelura, Niktimvo, Monjuvi and pipeline compounds like 989, our mutant-CALR, monoclonal antibody and povorcitinib, our JAK1 specific inhibitor, have the potential to drive future sales growth and form the company's core. More work remains, of course, but we've made progress with these compounds scientifically and commercially. Opzelura is showing strong broad-based growth today across AD and Vitiligo, has close to 20,000 prescribers and has the potential for new indications in the coming years. Niktimvo is off to a very strong start. Phase I results with 989 and ET are promising, and we will share data on MF at the end of the year. And finally, povorcitinib could support at least 3 different indications. Next, Incyte operates in 2 of the most structurally attractive markets in the industry: hematology-oncology and immunology. They're built on solid foundations of science, need and opportunity and we have differentiated knowledge and capabilities in these areas, and we'll focus on them. And finally, Incyte has well-developed high-quality R&D and commercial capabilities. Yes, there have been R&D setbacks, and we need to convert science into regulatory approvals and business results, but I believe our discovery and development capabilities in our core areas are a competitive advantage. Now regarding our strategic priorities, here's my initial thinking, and I will come back to you in the coming months with more specifics on the direction we plan to take the company strategically, operationally and financially. We intend to build a comprehensive plan for acceleration that goes beyond just filling a revenue gap. We'll take a fresh look at this business, including our R&D productivity, operating expenses and capital allocation and dedicate resources to accelerating product flow and growth. My framework for the business will likely have the following set of priorities. First, take care of the core, that's straightforward, driving utilization of our major products in the short term is necessary for long-term success. Second, accelerate product development. Pablo and I have spent many hours on this topic. It's almost all we talk about. Our mid- to late-stage pipeline has the potential to unlock the next phase of growth for Incyte but there are still unanswered questions, which is not uncommon. 989 is arguably the most scientifically promising asset in the MPN space. as a targeted mutation-specific approach. Our success will depend on translating early Phase I data into a regulatory approval and a marketed product, the medical need and the market potential for 989 is significant. If we're successful, 989 should trigger a fundamental shift in the treatment of MPNs like we've seen in other cancers. For povorcitinib, we have a clear incredible path to turning this into a major product for Incyte. Its success will be predicated on execution in areas where povorcitinib can have differentiation such as HS, PN and Vitiligo. In HS, povorcitinib could be the first oral option, which is perhaps the most challenging disease in dermatology. It's not like IL-3 mediate psoriasis or L413-mediated AD. It's more complex, involves more pathways, treatment success is variable. And so a new treatment option like povorcitinib should be very marketable. As it relates to our early-stage pipeline, the scientific rationale behind CDK2, G12D, TGF-beta/PD1 for select solid tumors, among others, is strong. But as you know, early-stage projects inherently involve uncertainties. We will be continuously assessing these and other programs. They'll be put through a framework to be scored and compared to other programs based on strategic importance, PTRS, commercial potential and return on investment. And I recognize that every use of capital, R&D capital is an opportunity cost for other users. Third, capital allocation. We're generating significant cash flow and have a growing balance sheet. The first call on capital will be the core business, our marketed products. The second is the late-stage pipeline and the third is business development. Sometimes our best investments will be inside the company. And other times, the reverse will be true. We'll have a governance mechanism for allocating capital internally and externally to ensure long-term growth and maximize shareholder value. Regarding business development, we'll look hard at finding derisked pre-revenue or revenue stage opportunities. As you know, there are very few positive asymmetrical opportunities out there, and it is easy to mistakenly turn $1 into $0.50. We'll be careful about where and how much capital we put to work. But when strategically sourced appropriately priced and well executed, BD can create a lot of value. We will have a well-defined framework for BD, and we will look for opportunities that fit that framework. Finally, it's important to keep a close eye on execution, converting science and strategic plans to results is the job. We'll run the business at a detailed level, enhance the quality and speed of decision-making inside the company and manage our expenses in a disciplined way, which means focusing on doing more with less versus more with more. I Look forward to sharing more details on our strategic framework later this year. Now moving to our second quarter results, which Christiana will review next. Jakafi demand remains very strong across 3 indications. Opzelura growth was exceptional across 2 indications, and the Niktimvo launch is exceeding expectations with rapid adoption among BMT centers, reinforcing its commercial potential. The growth prospects for these products are excellent if we continue to execute. On the R&D front, we made excellent progress. We will release Phase I data on 989 and MF at the end of the year to supplement the data we presented at EHA in ET. We expect an FDA approval for Opzelura in pediatric patients 2 to 11 years of age with mild- to-moderate AD in September. And importantly, the pivotal trials for povorcitinib in vitiligo and PN and combination trials with axatilimab in GVHD are enrolling on track. With that, I'd like to turn the call over to Christiana, who will provide the second quarter commercial and financial update.

Thank you, Bill, and good morning, everyone. In Q2, we delivered strong financial results with total product revenues of $1.06 billion, representing an increase of 17% year-over-year, driven by continued demand growth for Jakafi and Opzelura as well as the contribution from the ongoing commercial launch of Niktimvo. Total revenues were $1.22 billion, up 16% versus the same period last year. Turning to Jakafi on Slide 9. Jakafi net product revenue was $764 million for the second quarter, representing an 8% growth year- over-year, driven by paid demand, which also increased 8% versus the prior year period. Demand for Jakafi continued to grow across all indications. Channel inventory levels ended the quarter with a normal range. As a result of the strong demand seen in the first half of the year, we are raising our full year revenue guidance for Jakafi to a new range of $3 billion to $3.05 billion. Turning now to Opzelura on Slide 10. Total net product revenue for the second quarter was $164 million, representing a 35% increase year-over-year. U.S. net product revenue of $132 million was up 19% year-over-year, driven by increased patient demand and refills in both atopic dermatitis and vitiligo. Channel inventory levels ended the quarter with a normal range. Ex U.S. net product revenues of $32 million loss were driven by continued uptake in France and Germany as well as the recent launches in Italy, Spain and Canada. In France and Italy, Opzelura has seen very rapid adoption. Turning to Slide 11 and Niktimvo launch. Niktimvo net product revenues in the second quarter were $36 million, driven by high patient need and strong commercial execution. We continue to see positive launch metrics with widespread product awareness and interest. We have achieved roughly 82% account penetration with rapid and broad uptake in BMT centers across the U.S. Since the beginning of the launch, over 4,000 infusions have been administered to an estimated 700 patients, representing approximately 10% of the third line plus GVHD market. Of all the patients that went on Niktimvo, approximately 80% to 90% remain on therapy today. Turning now to other hematology/oncology products on Slide 12. Net product revenues for the second quarter were $131 million, representing a 66% year-over-year increase. This is primarily driven by the commercial launch of Niktimvo as well as increased contribution from

Thank you, Christiana, and good morning, everyone. As we highlighted a year ago when we summarized on this slide, our portfolio remains on track to deliver more than 10 launches by 2030. Moving to Slide 16. The Phase I data in essential thrombocytemia for INCA033989, our mutant-CALR monoclonal antibody was presented at EHA 2025. 9a89 is the first truly targeted therapy for a subset of patients with MPNs that includes 25% of patients with essential thrombocytemia and 35% of patients with myelofibrosis. Importantly, this data set demonstrated the normalization of platelet counts in patients with ET, which is consistent with the mechanism of action of 989 and a key point of differentiation from cytoreductive therapies. 989 was very well tolerated with only one out of 49 patients discontinued therapy. It is very reassuring that at this point in the development of 989, it appears to have an excellent safety profile. We also observed rapid and sustained reductions in VIF in most patients despite the short follow-up for patients in the highest dose cohorts. We believe this data will continue to improve as it matures, delivering an important outcome for patients. Treatment with 989 also resulted in a reduction in mutant-CALR positive megakaryocytes in the bone marrow as well as a reduction in mutant-CALR positive, CD34 positive stem and progenitor cells in peripheral blood, confirming the potential of 989 to be a disease-modifying therapy that offers a potential path to a cure. On Slide 17, let me summarize the key steps for the 989 development plan. We will advance this program with great urgency with the goal of starting pivotal trials in ET by early 2026. We continue to gather data and have expanded certain dose cohorts to better understand what the optimal doses for further development. We are committed to presenting data in MF as monotherapy and in combination with ruxolitinib by the end of the year. Additionally, we have established a collaboration with QIAGEN to develop a co-diagnostic across MPN, with an initial focus in CALR mutations. Importantly, we continue to develop a subcutaneous formulation, and that work is ongoing. We believe that initially, the IV formulation every 2 weeks is acceptable, but we'll work to advance a subcu in parallel. Turning to our dermatology portfolio, starting on Slide 18. I'm pleased to share an important update on ruxolitinib cream. As you know, Opzelura currently approved in the U.S. for the treatment of adult and adolescent patients with mild to moderate atopic dermatitis and vitiligo and in Europe for the treatment of vitiligo. Today, we announced the top line results from the pivotal Phase III TRuE-AD4 study which evaluated ruxolitinib cream in adult patients with moderate atopic dermatitis with extensive body surface area involvement of 10% to 20% and significantly impaired quality of life with a DLQI greater than 10. I'm happy to report that the TRuE-AD4 study met its co-primary endpoints at week 8 with statistically significantly larger proportion of patients receiving 1.5% Rux cream compared to vehicle, achieving both IGA-TS and EASI75. At week 8 Rux cream demonstrated a vehicle adjusted difference in IGA-TS of 47.6% and a vehicle adjusted difference in EASI75 of 51.4%, both highly statistically significant. In addition, the study met all key secondary endpoints, further reinforcing the efficacy profile of ruxolitinib cream in this patient population. Importantly, the safety profile observed in TRuE-AD4 was consistent with previously reported data in atopic dermatitis. Ruxolitinib cream was well tolerated, and no new safety signals were observed. This result confirms that ruxolitinib cream is a highly effective treatment option for patients with moderate AD who are eligible for systemic therapies. Based on the results of the study, plans are underway to submit a Type 2 variation for Opzelura in Europe, where there's a strong demand for innovative topical therapies in patients that have failed topical corticosteroids or topical calcineurin inhibitors. Looking ahead, we plan to present the full Phase III top line results at an upcoming medical meeting, and we look forward to engaging with regulators to discuss next steps for potential label expansion. Moving to Slide 19 and the near-term opportunities for povorcitinib. We're advancing povorcitinib in 3 indications and believe this represents significant opportunities for near-term revenue and long-term value creation. The positive Phase III data in patients with moderate-to-severe HS, which affects over 300,000 patients in the U.S. will be our first submission for povorcitinib and will support worldwide regulatory filings in 2026. The Phase III studies in patients with vitiligo and prurigo nodularis are progressing well, and we anticipate presenting data in 2026 with potential approvals in 2027. 2025 is a pivotal year for Incyte with over 18 key milestones, including 4 new product launches, 4 pivotal trial readouts, at least 3 Phase III study initiations and 7 proof-of-concept study results. As shown on Slide 20, we have already achieved several of these milestones with multiple important catalysts still to come. I would like to note that the initiation of our BET Phase III study is now planned for the second half of the year, pending regulatory feedback and the release of V617F Phase I data has shifted from the second half of 2025 to the first half of 2026. We look forward to sharing additional updates on these milestones in the second half of 2025. I will now turn it back over to Bill for his closing remarks.

Thanks, Pablo. To summarize the key takeaways before we open the line for Q&A. Our second quarter sales and growth for our key products were strong, resulting in revenue guidance being increased for the full year. Next, we are making excellent progress with our R&D pipeline, both for hematology/oncology as well as for I&I. Lastly, our focus is converting science and strategic plans into product flow and generating durable revenue and cash flow. That concludes our prepared remarks. Kevin, please open up the line and give your instructions for Q&A.

[Operator Instructions] Our first question today is coming from Jay Olson from Oppenheimer.

Welcome to Bill. It's a pleasure to reconnect with you, especially after having had the pleasure of working with you in the past. Thank you so much for outlining your strategic vision and the rigorous prioritization process that you're planning. Can you just share with us your thoughts on the relative importance of the 3 therapeutic areas at Incyte oncology, hematology, immunology. Do any of those get prioritized in your strategic plan? Or are you agnostic to therapeutic area?

Yes. Look, it's a good question, Jay. It should be pretty clear to everybody that MPNs is our most important therapeutic area right now. I think we have, as a company, an asymmetrical advantage in that space. I believe there's a window of opportunity here to completely transform the treatment of that group of blood cancers. As you know, targeting driver mutations in MPNs is the Holy Grail. I mean if you talk to a hematologist and ask, would you rather use a targeted monoclonal antibody versus a pathway approach, they'll select the target approach every time. We have, potentially the ability to create a series of innovations. Obviously, starting with 989, we have 617. We have a bispecific, we also have compounds in discovery. And when you have an opportunity to sort of dominate and control and never see the market, you got to take advantage of it. And so strategically speaking, that is our #1 priority. And I think we can set a new standard of care in MPNs, set what I would describe as a new high watermark. Now look, no one should take my word for it. We have to convert, as I said, science into results. And of course, the progress that we're making with 989 has been incredibly important. I think in I&I, I do believe that there's a credible path to building a large product. We're not, for example, with povorcitinib, copying all the indications for RINVOQ. And I do believe we have differentiated knowledge and capabilities in the 3 immune-mediated skin conditions that we're targeting. And we do have a franchise strategy with Opzelura and povorcitinib which other companies don't have. The product has the potential to be first in HS, first in vitiligo. And I think prurigo nodularis was a disease made for JAKs. And so I like the potential there. And as it relates to our oncology business, Jay, there are certain principles that you have to apply, find the right product first, pick a winning market and make sure that you can defend that position. And we will apply those principles and make sure we make good decisions as it relates to the other programs that we're developing for solid tumors. Beyond those 3 areas, look, the pressure to fill a pipeline in biopharma. This is true not just at Incyte, but it's true that every company is pretty unforgiving. We're focused on these areas right now. If we were to look at other areas, it would have to make sense strategically and operationally, and I would never stretch the capabilities of the company. But at the end of the day, what we're solving for is new product flow and the knowledge and skills we have in those 3 areas can be transferable.

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

I just wanted to get a sense -- maybe this is for Pablo on some read-through from the mCALR data that you saw from ET and what to maybe expect to see for MF? And then related to that, you're going to show monotherapy as well as combo, but is there a minimal threshold that you're looking for, for activity on monotherapy, if you could just help set expectations for that, we'd appreciate it.

Thank you for the question. Look, let me make a couple of comments here. The important thing to remember is, mechanistically, mutant-CALR antibody 989 would work the same way in MF that it does in ET. So whatever once preconception on the probably a success was before the ET data, it certainly has to increase with AT data in hand, a, because of the safety that was so clean and b, because the efficacy, not only the clear normalization of platelet reduction in VIF and reduction in mutant-CALR positive megakaryocytes was so clear in the ET data but because those were our fundamental based on the mechanism of action of the mutant- CALR antibody. So when we have that mechanistic clarity in a set of patients, the probability that will work on a different disease with the same molecular basis, is certainly high. The reason why we decided to shift the release of the data in MF to later this year is, as you pointed out, because we want to have combination data with ruxolitinib. As we all know, ruxolitinib increases survival in first-line patients in patients with MF. And so we believe that the development of 989 in MF will be at least in part in combination with Rux, which is why we wanted to have a more comprehensive data set when we present the data later this year. In terms of specific numbers, what I would say is we would expect to see improvement in MF in all the basic endpoints that we've discussed over the years in MF patients. Obviously, spleen size reduction -- spleen volume reductions, improvement in symptoms, improvement in hemoglobin, perhaps and we expect to see a component of that in the data release later this year.

Next question is coming from Salveen Richter from Goldman Sachs.

Just a follow-up to 2 comments that were mentioned earlier. One is initial data for 617F is now expected in the first half of '26. And should we read anything into this delay? And then secondly, you talked about the enthusiasm for povo in the HS market and its competitive differentiation. Maybe just walk us through that, particularly when you look in the context of superior efficacy that we've seen for some of the currently approved therapies such as BIM

Great, Salveen. I'll answer the second question, and Pablo, why don't you take the first question.

Certainly. So, this is simply related to the fact that this is a Phase I dose escalation study. And you make projections when you start the studies about what dose will give you a certain exposure that will be sufficient in this case, to reach the IC-35, which we've been talking about over the years about inhibiting the mutated cells. It turns out we need higher doses than we expected, you always need a certain amount of follow-up in these patients. As you know, in MF, data needs to mature a little bit. Because of those 2 reasons, the data has moved to the first half of 2026. Importantly, we have opened the study also now to patients with ET and PV. So the study is progressing well. We simply need higher dose levels with a longer follow-up to get the kind of data that we're willing to release. Our conviction of the mechanism on this program continues to be strong, and this is simply a matter of escalating a little bit further.

And then Salveen, on HS and povorcitinib and if Mohamed -- excuse me, Matteo has any comments he can add. First of all, as you know, it's one of the most challenging conditions in dermatology, ask any dermatologists that IL-17s don't work almost half the time. One dermatologist described high-score 50 or even 75 as a beauty contest. It's very hard to compare high score rates from one study to the next. The condition, as you know, is fundamentally different than IL-23 mediated psoriasis or IL-4/IL-13 mediated AD. That is to say it's inflammation suit. There are multiple pathways involved. If you ask a dermatologist, what's most important, they'll first say, make the patient feel better and then make them look better, meaning clearance. And this is a quality of life condition. If you look at the data from povorcitinib and you look at the effect that the drug has on pain and flare control, it's pretty remarkable, and it's a very competitive data set. It also does you get out past week 12 at week 16 or 18, those clearance rates are in the 50% range. And if you look at the effect of the drug across all those end points, clearance pain, flare control, half the effect is in the first 3 weeks. So I believe that a systemic option like povorcitinib is going to have a place in the treatment paradigm for HS. Whether they're starting with povorcitinib and then go into a biologic or they go to a biologic and then to povorcitinib. I don't think anyone has a clear view on the future, but this is a condition that there's a lack of treatment options, we have good data. And when you look at the totality of the evidence, there's going to be a place for povorcitinib as well as the IL-17s.

Our next question today is coming from Salim Syed from Mizuho Securities.

I guess maybe one for us on Niktimvo. So you had a good beat again on the quarter. And obviously, the J-code went into effect here around April -- April 1, I believe. Can you maybe just comment to some of the intra-quarter dynamics there that you saw from the JAK going into effect? Or do you describe the strength of the quarter to any other particular part of the launch? And I don't think you guys mentioned the inventory impact there for the quarter, for me just remind us what the inventory impact was for the quarter?

Yes. Thanks for the question. I'll give you my overall assessment and either Mohamed or Christiana can fill in some of the details. As Christiana said, we're 5 months in, and we're at a 10% penetration of that third, fourth line market. And what we watch on a weekly basis and which is important for any new product launch is what do your new patient starts look like. Every pharmaceutical products like a leaky bucket and you have to maintain -- the same is true with Opzelura. You have to maintain new patient starts. So when I look at the dynamics underneath Niktimvo, that's what I'm focused on. This product over the next 5, 6, 7 months, say, the balance of the year has the potential to reach over 1,000 patients. That would be a very, very good first year. If you take a look at the adoption curve, for example, of Sanofi' Rezurock and you look at the adoption curve right now for Niktimvo, they're both in the same

Yes, you didn't miss much. But I think here, Salim, it's just really important to just underscore that we're pleased with the performance so far. You heard earlier about 10% penetration in that third line plus setting. Also important to note that there's about 3,500 patients that are in play at any given time in the third line plus setting. That means these are the patients that are up for grabs that are changing therapy and some capacity. So we're either at 10% of the third line plus setting in total, over 20% of that in-play opportunity, which, again, is a testament of commercial execution. You heard some of the metrics around infusions and penetration from Bill. I think the last thing maybe I'd say is that we know prescribers are seeing real-world results, very similar to what they saw in our clinical trials, which is not always the case in this disease, and this is going to naturally encourage providers not only to use Niktimvo more often, but perhaps also consider Niktimvo earlier in their treatment paradigm for more patients.

Just on inventory. Can you just comment on that?

Yes, the inventory, just to put that in perspective, inventory accounted for less than 5% of Q2 sales so far, and that's stabilizing in that expected range. So the performance that you're seeing and the volume is driven primarily by demand.

Next question is coming from Kelly Shi from Jefferies.

This is Clara on for Kelly. So you have the initial G12D and bispecific data presenting at ESMO. Whether you can provide more granularity on the scope of proof-of-concept data? And maybe help us understand what would be the key metrics you're looking for to define success and move the program forward.

Great. Pablo, do you want to take that?

Certainly. So -- what we should expect -- what you should expect for the 2 presentations at ESMO in a way, it's consistent with what we did last year with CDK-2. As we've made -- we try to be disciplined about presenting data. We want to present substantial data sets to give you clarity on how well this compounds work in terms of both efficacy and safety and to be able to have with you a discussion about next steps for the programs. And that's exactly what you should expect here. We're going to have a substantial number of patients for both our KRAS G12D program and our TGF-beta receptor like PD-1 receptor by PD-1 bispecific. And we believe that both demonstrate proof of concept in a range of tumor types and the amount of data we'll be able to use that to have a discussion with you on the next steps for these 2 programs, which we expect to do at ESMO in the next couple of months.

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

And welcome to Bill, look forward to working with you. So question of Opzelura. I know your guidance was unchanged, but I wanted to unpack the dynamics underlying that. And I'm curious the degree to which pediatric indication is embedded there. And then maybe how we should be thinking about the ex U.S. cadence going forward? I know you saw a big uptick but international can be a bit lumpy. And then maybe longer term, the degree to which the moderate AD data from TRuE-AD4 might expand the market opportunity down the road?

Yes, Brian, good question. I'll give you my initial observations after the first 30 days. Obviously, 60% of the business is AD and 40% is Vitiligo, right? That AD business is growing at plus 20% and the Vitiligo business is growing at plus 10%. Our penetration of this market, if you just think about the AD market as systemic and topicals, is still relatively modest, 7% of the overall AD market systemic and about 17% of the topical market, right? Market's grown at 20% year-over-year because of migration from topical corticosteroids to a nonsteroidal option, topical or systemic. And that TCS market in the United States at branded pricing is about $15 billion. right? Now it's moving at a modest rate, but that's what's fueling the growth of the market that they're in. And as I said, I see it as a -- I see this as a double-digit CAGR business both U.S. and of course, internationally over the next several years, just with AD and with Vitiligo. As it relates to pediatric, I would think about it as an incremental growth driver, all right? Here's what we know. There's about $2 billion in triamcinolone use at branded pricing in the United States. But I think we have to be realistic about the extent to which we're going to drive utilization in pediatrics. I think the core business right now is what's going to drive growth over the next several years. The product's got 20,000 users in the United States, prescribers, which is second to only DUPIXENT in AD. And so there's a large prescriber base hearing when you're thinking about the long-term growth potential of any product, that's important. And then as you know, the coverage both commercial, Medicaid and Medicare is solid. It's not cheap, but it's solid coverage. And so I like the way it looks. As it relates to the international business, I just spoke with the person who runs our international business the other day about this. France, Italy, Germany and Canada, right? We had a good first or second year. It's gone from $60 million to roughly $120 million in sales. We'll get the AD -- that was just in Vitiligo. And the indication for AD has the potential to keep that business growing and maybe you to exit over several years? Pablo, anything you want to add?

No, you covered it all. And on the ped side, we see the same way. It's a great tailwind to sustain the growth of our already strong value proposition in that disease.

Our next question today is coming from Jessica Fye from JPMorgan.

A couple or more for Bill. Curious how you plan to balance investment in pipeline advancement relative to external opportunities relative to the need for investment to support kind of near-term commercial performance. And I guess, if we think about kind of looking out 5 years from now, how do you see Incyte? Is this going to be mainly organically grown, transformed through M&A, some kind of combination?

Yes. It's a really good question. I think there's a lot in that. Look, the job here, it's not just mine, it's Pablo and Steven and Christiana and the people who run the Commercial business, it's about forgive the baseball metaphor, it's about calling balls and strikes and you have to look at internal investments and external investments the exact same way. There are no sacred cows inside the company. It's also not true that everything outside the company is a shiny penny. And I've been here 30 days, but I will tell you all we think about is capital allocation, both internally and externally. In terms of the balance between the two, I don't like to force any ratio. I think we have to just look at facts, details and analysis and make our calls. As it relates to where I want to see the company in 5 years, it'd be nice to exit. But I think what we want to do is to -- and I mentioned this earlier, set a new high watermark for this company. I mean we have to get through 2029. But set new highs for the company, and that means getting our growth portfolio right, and I include that Opzelura and Niktimvo and then 989 and povo. And I know there's no guarantee there. We have to we have to manage those programs. Next, get R&D priorities right, which is what every company has to do, then get the cost base right. That's just good corporate hygiene. Get BD right and build the business for the long term so that we really never see the end of the road. And as I mentioned earlier, I do believe we have a win of opportunity in MPNs, where we have differentiated knowledge and capabilities to build a really great business there. Thanks for the question.

Next question today is coming from Marc Frahm from TD Cowen.

Maybe one quick one, clarifying in an earlier answer. Just on the threshold in MF for mutant-CALR. Even if maybe the best path forward is combinations, do you need to see kind of convincing monotherapy activity that if that was all you had would have justified moving forward as well in order to kind of move the program forward either as the monotherapy or as the combo? Or it's just convincing combo data enough? And then similar to that, maybe Bill, when you're talking through the kind of the way to think about prioritizing financial resources, you can put solid tumor oncology or oncology outside hem/onc as maybe the third priority. When you think about the G12D data coming, you guys are not first-in-class there necessarily. And the next steps are likely some combinations in addition to monotherapy work where this program really starts to blossom. Does it need to be a convincing best-in-class agent in order to justify that investment? Or is kind of over time competing in various combinations, but with a more similar asset enough to justify investment?

Good. Marc, thanks for the question. I'll turn over the first question to Pablo and then probably Pablo and I will take the second question together. Go ahead, Pablo.

So let me address the 989. And the short answer, Marc, is we absolutely have to have single-agent activity in MF. I think it's an expectation based on the mechanism of action of 989 that it will have single-agent activity in patients with myelofibrosis. The question here is as we build a comprehensive plan to basically cover the needs of every single patient with a myeloproliferative neoplasm, we want to make sure we can address early MF, first-line and patients with MF that failed on Jakafi, either for intolerance or progression on Jakafi. And to do that, we need a comprehensive data set to show you a single agent and combination data with Jakafi. But it's an expectation based on the mechanism of action of 989 that it will have single-agent activity in myelofibrosis.

Great. And as it relates to G12D and Pablo will also comment -- First thing I said is we're very clear eyed about this. There are dozens in development, and in the hands of big companies, the hurdle here is high, and we'll be clear eyed about making a decision. If you're not first, you're better be early and most importantly, the position has to be defensible, right? And when we get that data, we're going to have to make that decision. We do believe that the properties of G12D could be differentiating and we believe that it will have a place in the treatment paradigm. And I'll let Pablo talk a little bit about that.

So to complement what Bill said, this is, as you know, Marc, a very competitive space, G12D and there's some excellent programs advancing in this setting. Well, we think we have our G12D program, and we look forward to showing the data so we can discuss this in more detail we did in hand. It's a compound not only might be competitive in terms of single-agent activity, but a combinability might be better than some of our competitors. And when you think about the really, really big opportunity here, which is first-line pancreatic cancer, that's going to require more likely than not a combination therapy with intensive chemotherapy. In that context, we think we have a path to compete with some of the other programs. So as Bill said, we may not be first-in-class, but we're certainly in the front of the pack when it comes to positioning. And if the combinability of our G12D inhibitor is better than some of our competitors, perhaps there is a way to accelerate the development in early lines of therapy in pancreatic cancer. That's the way we're seeing the program. As Bill said in his introductory remarks, we will have a very high bar to continue to advance this program forward once we share all the data, and we'll make those decisions later this year.

Next question today is coming from Evan Seigerman from BMO Capital Markets.

This is Conor MacKay on for Evan. This is the second quarter in a row that Niktimvo has come in ahead of consensus expectations. And you shared a little bit today about kind of the dynamics in the early days of the launch. But I'm curious, maybe can you remind us how you're thinking about sort of the peak opportunity for this product? And kind of has the launch trajectory in the early days change that at all? And then I guess maybe just one quick follow-up for Bill as well. we discussed a little bit about business development and how you're prioritizing that versus the internal pipeline. I guess are there any therapeutic areas that you'd be most focused on sort of as it relates to business development.

Great. I'll take a shot first at the first question and then let Mohamed fill in, and then I'll come back to the second question. As it relates to the peak potential of Niktimvo, it's really hard to figure out what's going to happen in 5 years. I'm pretty modest about the accuracy of my future predictions. But I will tell you that, it's only 2 quarters, and I've been on both sides of this, positive and negative. I'm reassured by what I see. I think the potential of this product in part is going to trade on can we get it into combination with Jakafi and with steroids. And those studies are ongoing. That's number one. We also have a team working on a subcu formulation, which I think is very important. And that's going to get you into frontline, whether you're a monotherapy or whether you're a combination therapy. Now we have to take care of the short term and build a real solid business in the indication that we have today, and all estimates are that we're doing that. things can sort of wobble around quarter-to-quarter. But since your question was about the long term, my expectations are, when you look at a product like Rezurock at Sanofi, that could be the low watermark for us. And I think if you get these additional indications, then you're going to travel north of that. Mohamed?

Yes. Maybe just to quickly complement there. I think, look, in the first 5 months, we mentioned we've been able to capture 20% of that in-place segment. If by the end of the year, we can capture it to Bill's point earlier, 1000 patients, so let's call it, 30% of that in- play market, we'd be ahead of GVHD analogs and overcome any entry of -- order of entry discounts. So if you consider those same analogs then, I think it will be conceivable for just our indication that we have today to deliver several hundred million dollars of annual sales by 2028. So we're currently working ahead and performing ahead of analogs in the space. And I think we're performing to an extent where we're going to mute, I think, order of entry analogs to a certain extent, and I think you can put projections based on some of those analogs.

And as it relates to the second question, if you study companies that have great businesses, there are a couple of criteria that are common in terms of new therapeutic areas. And I'll just say upfront, we've never gone to a new therapeutic area that would stretch our capabilities or we would go beyond our competencies because I do believe right now we're in 2 excellent areas with excellent prospects for growth. But you look -- first of all, chronic disease management is -- has a lot of sort of attributes to it. You look for a fairly sizable population, unmet need, the potential to have a standard of care approach and where duration of therapy is measured in years, not months. And there are some logical extensions of our current business in hem/onc and immune-mediated skin conditions or I&I. And we'll continue to look at it. But my focus right now is on what we have. And if there's an opportunity to enter another therapeutic area that makes sense strategically operation financially. We'll explain it and do it, but the focus right now is what's inside the company.

Our next question today is coming from Srikripa Devarakonda from Truist Securities.

And Bill, let me extend my welcome, looking forward to working with you. I have a question on Jakafi in PV. You saw continued growth in PV. It continues to be -- Jakafi continues to be a key growth driver here. Can you talk about the patient population where you're seeing increased uptake? And also given the footprint you have established here, any thoughts on life cycle management beyond the XR and V617F, which we're going to see data, hopefully, next year would be helpful. And also one follow-up question. Monjuvi was approved for relapsed/refractory FL in June. Just any thoughts on expectations there for the remainder of the year?

Yes. Thanks for the question. I'll just go ahead and turn it over to Mohamed to address the question on Jakafi.

Yes. Maybe let me take a stab on Jakafi, Monjuvi, then Bill, I'll give it back to you for any added remarks. Look, PV is the least penetrated indication for Jakafi when compared to the other 2 indications, thus being our biggest growth driver. Our team is doing a very effective job in educating the market on the importance of treating PV earlier with Jakafi and its benefits of thrombosis-free survival. As a result, you continue to see strong double-digit growth in Q2, and we're confident in that momentum going forward. So there, the patient population is simply patients on an earlier-line therapy that are experiencing symptoms and/or need an intervention. And when using Jakafi for those patients, they benefit from thrombosis-free survival. If I can just quickly touch on Monjuvi, and then Bill, I'll give it back to you. Look, I think it's important to note Monjuvi showed a 59% risk reduction, disease progression or death versus what is currently the standard of care. So we believe naturally Monjuvi has the potential to be the new standard of care for patients living with FL and we expect the growth ramp, though, here to be reflective of the indolent nature of the disease, and our expectations for the balance of the year are captured in the guidance that Christiana provided for the other hem/onc portfolio, with really good execution Monjuvi in FL alone, excluding any other indication can be one of those incremental growth drivers and deliver $200 million or so in annual revenue by 2028.

Yes. I think Mohamed said it well, very focused on the growth of Jakafi over the next several years. Obviously, our penetration in MF is high. And as Mohamed said, in GVHD, I would describe it as medium. And then in PV, it's low, which is why you're seeing double- digit growth with that product right now or with that indication right now, I think we'll continue to see that. And the MAJIC-PV study is only a couple of years old. So -- thanks for the question.

Next question today is coming from Stephen Willey from Stifel.

Just a couple on 989. Can you say anything about the characteristics of the MF patients enrolled into the Phase I with respect to just baseline cytopenias, hemoglobin. Were there any restrictions placed on eligibility criteria? Or should we expect that this is going to look like a typical JAK experience patient population? And then just wondering how we should also be thinking about the duration of follow-up we'll have relative to what was just presented in ET.

Thanks for the question. Pablo will take it.

So the population is as you call the typical of patients have been exposed to Jakafi, there are patients that are intolerant or progressed in Jakafi. So it's a pretty representative population in MF. We were not very restrictive in terms of enrollment criteria. So I think it will be very informative in order to discuss next steps for 989 in patients with MF. Follow-up is going to be variable. This has been a dose escalation study, as you know. So the early dose cohorts will have longer follow-up than the later dose -- higher dose cohorts. But all in all, we'll have patients with pretty substantial follow-up because the study started enrolling patients at low doses more than a year ago. So we'll have a fair amount of follow-up.

Thanks for the question.

Our next question today is coming from David Lebowitz from Citi.

Bill, welcome to the team. I guess on Jakafi in the current quarter, what were the particular drivers -- which side of the -- which indication drove the therapy the most? I'm curious as to what IRA and the out-of-pocket changes might have had an impact in the quarter and how we should see that impacting going forward?

Yes, good question. I'll give you some initial comments and then Mohamed could take over. I think the most important point about the quarter is that there was growth in all 3 indications. And I think you can -- I would view MF and GVHD as mid-single-digit grower -- growing indications. And I think this is true over the longer term and PV as a double-digit growing indication. We saw that last quarter. We saw it again this quarter. And I think given where the product sits in each one of those markets or those indications, that's what the growth profile or the mix is going to look like for the next 3-plus years. And then as it relates to the IRA, Mohamed?

Yes, nothing to add on the growth drivers. On IRA, the simple answer is that it had no impact on our performance in Q2. As you remember, the IRA dynamics had a favorable GTN impact in Q1, but that was a onetime effect as we communicated there. And in Q2, the demand really drove the growth, and that's where you see the performance for Jakafi in the quarter.

Our next question is coming from Michael Schmidt from Guggenheim.

I just had another bigger picture question for Bill. So in terms of capital allocation and sort of reading between the lines and some of your prior comments, it sounds like there may be opportunity to perhaps optimize the earlier-stage R&D portfolio. So longer term, as you think about potentially increasing R&D productivity for the company, are there specific areas where you think Incyte is underinvested, be it in terms of targets, modalities or disease areas within the broader framework of oncology and I&I. And then just a quick one for Pablo on povorcitinib. Just could you just help us understand the importance of the upcoming Phase II data in asthma in the second half of the year? I know you've noted in the past that the bar is high to advancing this, but yes, just curious what we should expect there.

Yes, Michael, good question. Listen, Pablo and I speak a lot about the first question that you just asked regarding specific areas, putting external opportunities aside. As soon as I make a comment about an area, the prices of all those companies would go up. But why don't you just talk about how we're thinking about internal R&D and oncology.

So if I understand your question, Michael, it's more specifically related to the early preclinical pipeline. And what we've been doing there, a lot of which is honestly not visible because we don't disclose pre-IND programs. But we have, over the past couple of years, increasingly tightened our focus around novel biology and applying novel platforms to novel biology. So our goal over time is to truly focus on try to be first-in-class applying novel platforms. And that was the impetus behind the collaboration we established with Genesis to take advantage of the capabilities on AI, machine learning drug discovery. The collaboration that we put in -- we expanded with BioTheryx to have access to a molecular glues library. And we will continue to do those because we believe, fundamentally, in order to win the next 10 years, we need to focus on novel areas, novel targets by applying novel platforms. So that's a lot of the emphasis when it comes to the preclinical pipeline. There was a question on asthma. So -- this remains a really important potential indication for povo. We think there's a type of patients, particularly those with non-type-2 asthma, where there remains a need to reduce exacerbations and deliver substantial improvements in FEV1. And I'm talking about over 100 to 150 mL. So we are really excited about having this data later this year. It's been a program that has not received a lot of attention. So we look forward to deliver results before the end of the year. And depending on those results, obviously discuss next steps.

Our final question today is coming from Gavin Clark-Gartner from Evercore ISI.

Very quick one. For 989 should we expect updated ET data alongside the MS data later this year?

Yes, Gavin, it will be an update on ET data as well later this year, absolutely. We are -- as I mentioned in my remarks, we're moving as quickly as we can in ET. We will obtain later this year regulatory feedback with the goal of starting pivotal trials early 2026. So we will provide an update on the ET data that we'll present at AHA later this year.

We've 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 and for your questions, the IR team will be available for the rest of the day for follow- up. Thank you, and goodbye.