Incyte Corp

NASDAQ:INCY

Earnings Call Transcript 2024-Q1

[Operator]

Hello, and welcome to the Incyte First Quarter 2024 Earnings Call. [Operator Instructions] As a reminder, the 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.

[Ben Strain, executive]

Thank you, Kevin. Good morning, and welcome to Incyte's First Quarter 2024 Earnings Conference Call. Before I 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 call. On today's call, I'm joined by Herve, Pablo, Christiana, who will deliver our prepared remarks; Barry, Steven and Matteo 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 Herve.

[Herve Hoppenot, executive]

Thank you, Ben, and good morning, everyone. Before I get into the quarterly results, I'm pleased to share that Matteo Trotta, has recently joined Incyte as General Manager of our U.S. Dermatology business unit reporting to me. Matteo comes to us from Novartis where he was responsible for the immunology business in the U.S., and he will be leading the U.S. Dermatology team at Incyte to continue to grow Opzelura, prepared for the launches of povorcitinib and other promising IAI pipeline product in the coming years.

Now turning to our Q1 results. Total revenue grew 9% in Q1 versus last year, and I will discuss in the next slide the details of the underlying demand growth for Jakafi and Opzelura to clarify the performance of both brands in Q1.

Starting with Jakafi on Slide 6. In the first quarter, Jakafi net product revenue of $572 million does not fully reflect the demand growth as total patients increased 5% in the first quarter versus the same quarter last year, with growth driven by PV and GVHD. Sequential growth versus Q4 was also strong in all indications, as you see on the graph on the right.

Jakafi channel inventory reduction in the first quarter had a negative impact on net revenues of approximately $55 million. Based on the strong patient demand since this quarter, and anticipated growth for the balance of the year, we are reiterating our full year 2024 Jakafi net revenue guidance of $2.69 billion to $2.75 billion.

Turning to Slide 7 and looking at Jakafi total paid demand by indication during the first quarter of '22, '23 and 2024. As you can see, total paid demand growth in the top left corner continues to be strong. MF in the top right is consistent year after year, and the largest growth is coming from PV and GVHD.

Additionally, Jakafi continues to maintain its leadership and market share in myelofibrosis. Based on market research, total patient market share and discontinuation rates have remained stable in the first-line setting over the past several months, with virtually no impact from competitors, which has been consistent with our expectations.

Moving to Opzelura. Total Opzelura net product revenues in the first quarter were $86 million, up 52% when compared to the same quarter last year. The weekly prescription trend, as shown on the right of Slide 8, reflects continued growth of Opzelura in both atopic dermatitis and vitiligo, with typical Q1 seasonality. U.S. total prescriptions for Opzelura grew 41% year-over-year, outpacing the total ED market, which grew 23%. The ED market, including Opzelura was impacted by the Change Healthcare cyber-attack, particularly in March. Importantly, we are beginning to see in April a rebound in filled prescription to levels seen before the cyber-attack.

From an access perspective, we have seen early encouraging results since Opzelura moved in January to preferred position in the [ CBS ] network as TRx growth within the CBS network outpaced growth in other plans.

Moving to Slide 9. As discussed in the past, we are on track to provide 10 high-impact launches by 2030. Importantly, many of the programs highlighted on this slide are derisked as they are post proof of concept, including axatilimab, which has been submitted to the FDA for approval, ruxolitinib cream in Pediatric AD to be submitted to the FDA in Q3, and povorcitinib, where we are in Phase III in HS and vitiligo and initiating a Phase III study in prurigo nodularis later this year.

Moving to Slide 10. In addition to our internal efforts to deliver multiple launches by 2030, we recently announced an agreement to acquire Escient Pharmaceutical for $750 million with cash on hand. This acquisition further strengthens our pipeline with 2 novel first-in-class medicines, EP262 and EP547, which has the potential to treat a broad range of inflammatory disorder.

I will now turn the call over to Pablo.

[Pablo Cagnoni, executive]

Thank you, Herve, and good morning, everyone. In the first quarter, we continued to make solid progress across our pipeline, which is focused on 3 areas: MPNs and graft-versus-host disease, oncology and inflammatory diseases.

In MPNs and graft-versus-host disease, we initiated a Phase I study earlier this quarter with a JAK2V617F inhibitor. As a reminder, the JAK2V617F mutation is the most common somatic mutation in myeloproliferative neoplasms and is present in 55%, 60% and 95% of patients with MF, ET and PV, respectively.

Unlike ruxolitinib, which inhibits both wild-type and V617F mutation positive cells, 058 selectively binds to the JAK2 JH2 site, disrupting the V617F induced confirmation and thus allowing selective inhibition of mutant activity in the JAK2 receptor while sparing wild type. Together with our anti-mutant CALR program, these 2 potentially disease-modifying programs represent a fundamentally new approach to addressing MF, ET and PV, and could help to solidify our leadership in MPNs.

As previously disclosed, we submitted a BLA for axatilimab for the treatment in third-line chronic graft-versus-host disease late last year. In February, the filing was accepted for prior review and we anticipate a decision by the FDA in the second half of 2024. We are excited by the possibility of bringing a new treatment options to patients with this devastating complication of hematopoietic stem cell transplant.

In oncology, we continue to build out a robust pipeline with the potential to deliver meaningful innovation for patients. This quarter, we initiated a Phase I study with our KRASG12D inhibitor, INCB161734. 734 is a potent, selective and orally bioavailable KRASG12D inhibitor. And as highlighted at AACR earlier this month, it has shown excellent efficacy in several preclinical models.

With no currently approved G12D targeting agents, 734 could address an important patient need as the KRASG12D mutation is found in 40% of pancreatic ductal adenocarcinoma, 15% of colorectal cancers and 5% of non-small cell lung cancers.

In dermatology, we continue to maximize the potential of ruxolitinib cream and povorcitinib and believe the acquisition of Escient Pharmaceuticals will substantially expand our IAI pipeline by adding 2 first-in-class medicines with the potential to address a number of medical needs.

The key driver of our interest in Escient is our MRGPRX2 program. MRGPRX2 is a specific novel mechanism for blocking mast-cell activation independent from IgE and has been a high-priority target to add to our IAI pipeline. EP262 is a first-in-class medicine, which entered the clinic in January of 2023 and has been evaluated in Phase II studies.

In the Phase I healthy volunteer study, EP262 was well tolerated, had low interpatient PK variability, and achieved exposures well above predicted efficacious levels. EP262 is currently in a Phase Ib open-label study in CIndU and in 2 randomized Phase II studies in CSU and atopic dermatitis, with data for all 3 studies expected by early 2025.

EP547 is a potent and highly selective antagonist of MRGPRX4. MRGPRX4 is expressed on neurons in the dorsal root ganglia and specifically activated by bile acids that are increased in cholestatic patients. Initial evaluation is being conducted in cholestatic pruritus with clinical proof of concept for cholestatic pruritus associated with PBC and PSC, anticipated by early 2025. A number of exciting readouts are expected by early 2025 with a potential first launch in CSU by 2029.

At AAD earlier this quarter, we presented additional data from the randomized Phase II study of ruxolitinib cream in patients with mild to moderate hidradenitis suppurativa reinforcing the potential ruxolitinib cream in this indication. The study met its primary endpoint, demonstrated a significantly greater reduction in abscess and inflammatory nodule count compared to control at week 16, and further reinforces the efficacy and safety profile of ruxolitinib cream. We are currently engaging with the FDA to obtain agreement on a potential Phase III design.

We also presented positive data at AAD from the randomized Phase II study evaluating povorcitinib in patients with prurigo nodularis and are on track to initiate a Phase III study in the coming months. As highlighted on Slide 21, the study met its primary endpoint of a 4-greater-point improvement in the Itch Numerical Rating Scale score, which was achieved by significantly more patients, who received povorcitinib across all dosing groups at week 16 versus placebo.

We believe that with ruxolitinib cream and povorcitinib, we will be the only company with the ability to potentially provide both a topical and oral option for a number of indications, including prurigo nodularis, hidradenitis suppurativa and vitiligo.

We continue to make important progress in the first quarter by achieving several clinical and regulatory milestones. Within our oncology pipeline, we believe that our potentially best-in-class CDK2 inhibitor is an active agent, and we look forward to sharing data as well as our development plan later this year.

In addition, the pivotal trial of tafasitamab in patients with follicular and marginal zone lymphoma, also known as inMIND, will read out later this year, and we look forward to sharing those results.

With the BLA for axatilimab submitted late last year, we look forward to working with the FDA to make axatilimab available to patients with chronic graft-versus-host disease later this year and to initiate additional combination studies in patients with less pretreated chronic graft-versus-host disease.

Within our dermatology portfolio, we expect to submit the sNDA for Opzelura for pediatric atopic dermatitis and expect multiple data readouts throughout the year. With that, I would like to turn the call over to Christiana for the financial update.

[Christiana Stamoulis, executive]

Thank you, Pablo, and good morning, everyone. Our first quarter results reflect continued strong growth with total revenues of $881 million, up 9% versus the same period last year. Total product revenues of $730 million in Q1 were driven by demand growth for Jakafi and Opzelura and increase revenue contribution from Monjuvi following the acquisition in February of the global exclusive rights to tafasitamab. The product demand growth was partially offset by an anticipated reduction in channel inventory for Jakafi and the typical Q1 dynamics for Jakafi and Opzelura.

Total royalty revenues, which are primarily comprised of royalties from Novartis for Jakafi and Tabrecta and royalties from Lilly for Olumiant were $126 million, up 9% compared to the quarter of 2023, driven by strong demand for Jakafi. Total revenues included $25 million upfront payment received under our collaboration and license agreement with CMS for the development and commercialization of povorcitinib in China and select other Asian countries.

Turning to Jakafi on Slide 26. Jakafi net product revenues were $572 million for the first quarter. Net product revenues reflect continued demand growth with total patients up 5% year-over-year, driven by growth in PV and GVHD and continued stable demand in MF. As a result, we experienced the highest quarter paid demand for Jakafi since launch.

As expected in Q1, we saw patients that were on free drug in the fourth quarter of 2023 returned to paid demand and a related decrease in channel inventory levels. As you may recall, channel inventory levels increased by $46 million in the fourth quarter of 2023.

In the first quarter of this year, we saw a drawdown in channel inventory, which had $55 million negative impact on net sales versus the first -- fourth quarter of 2023. While we expect channel inventory to remain around the levels we ended in Q1, buying decisions of our customers can't always be predicted.

In addition, net sales in the first quarter were impacted by the typical Q1 higher gross net deductions as a result of both contributions to close the Medicare gap and commercial copay assistance.

Turning now to Opzelura on Slide 27. Net product revenues for the first quarter were $86 million, representing a 52% increase year-over-year, driven by growth in net new patient starts and refills across both AD and vitiligo as well as early contribution from the commercialization of Opzelura for vitiligo in Germany, Austria and France. As expected, Opzelura net product revenues in the first quarter reflected the typical Q1 seasonality and the reset of deductibles and copays at the beginning of the year. Beyond the typical Q1 dynamics Opzelura product revenues were impacted by the cyber-attack on UnitedHealth Change Healthcare unit.

Moving on to Slide 28 and our operating expenses on a GAAP basis. Total R&D expenses were $429 million for the first quarter, representing a 6% year-over-year increase, which was primarily as a result of the progression of our pipeline. Total SG&A expenses were $300 million for the first quarter, representing a 5% year-over-year decrease driven by the timing of direct-to-consumer marketing activities and certain other expenses.

Now turning to the acquisition of Escient Pharmaceuticals. Under the terms of the agreement, we will acquire Escient for $750 million in an all-cash transaction. We believe Escient 2 lead programs offer a multibillion-dollar potential, commercial opportunity across multiple indications and have the potential to contribute to our revenue by 2029. In addition, we expect to be able to realize synergies by leveraging our current development and commercial capabilities and infrastructure. We anticipate the acquisition to become effective by the third quarter of 2024, and other approximately $5 million per month in incremental R&D expense. Depending on the timing of the close, we expect the acquisition to add $20 million to $30 million to the full year 2024 R&D expenses.

Finally, following this acquisition, we'll continue to have a strong balance sheet, which will -- allows us to consider additional opportunities. As of the end of the first quarter, we have $3.9 billion in cash and no debt.

Moving to our guidance for 2024. Excluding the impact of the acquisition of Escient, we are reiterating our full year 2024 guidance for Jakafi, our other hematology/oncology products, COGS, R&D and SG&A.

Operator, that concludes our prepared remarks. Please give your instructions and open the call for Q&A.

[Operator]

[Operator Instructions] Our first question is coming from Kelly Shi from Jefferies.

[Dingding Shi, analyst]

So for Opzelura, could you give us some more color on the gross-to net for the rest of the year? And what is the latest review you see in both AD and vitiligo? And I also have a follow-up.

[Christiana Stamoulis, executive]

Kelly, it's Christiana. Let me take the first part of the question, and then I will turn it to Matteo to comment on the second part. So in terms of the gross-to-net in the first quarter, it was at the same level as last year Q1, so at around 60%. Going forward, as we have previously discussed, we will not be making forward-looking comments on gross-to-net. Our focus is on maximizing the potential of Opzelura, and by this, I mean the maximizing net sales versus looking at gross-to-net in isolation.

[Matteo Trotta, executive]

And on the split of business between the 2 indications, when we look at the IQVIA data, triangulated with external and internal sources, we see a 40-60 split consistent over time, where 40% is non-segment of Vitiligo and 60% is atopic dermatitis. And we're very happy to see that both indications are growing at quite a healthy pace.

[Dingding Shi, analyst]

And also at AAD Dermatology conference, we saw the data of topical [ ruxolitinib ] cream in both Hurley Stage I and II, HS patients. Could you share what kind of physician feedback do you hear? And also, how do they see or manage in both Hurley Stage I and II and 2 patients for novel topical drug like Opzelura needed to manage disease in this specific population?

[Steven Stein, executive]

Yes. Thank you for the question. It's Steven. So the milder type of HS still represents about 100,000, 150,000 patients in the United States. It still has morbidity and unmet need, and these patients have abscesses and nodules that cause them discomfort and morbidity and lends itself to a topical treatment because it's not as extensive as the moderate and severe, which has fistulas, et cetera. So we conducted this PoC study and saw this data, which is extremely encouraging in this mild stage of HS in terms of abscess and nodule decreases. And as Pablo said in his prepared remarks, we're now working with regulators to get an appropriate endpoint in this entity for which no drug is approved and has this unmet need I spoke about.

To the specifics of your question, the physician and KOL feedback is excellent. I mean they were surprised by the efficacy seen with topical agent in this entity. So we're excited about it as well.

[Operator]

Your next question is coming from David Lebowitz from Citi.

[David Lebowitz, analyst]

Could you comment on Jakafi growth dynamics going forward given IRA and shift to the out-of-pocket expenses for patients?

[Barry Flannelly, executive]

Sure. As you saw from our guidance, $2.69 billion to $2.75 billion, we're very optimistic about the continued growth of Jakafi. Obviously, we benefit in the IRA because as we talked about before, we have the small biotech exemption.

So beginning in 2025, for example, with the reduced out-of-pockets for patients, it really just helps the patients, of course, but we don't have to contribute that 20% to catastrophic that other oral drugs will.

So we think there is a benefit in 2024 for the reduced out-of-pocket in Medicare Part D being around [ $32.50 billion ] for patients for the entire year and then next year, being [ 2000 ] all patients who are taking oral oncology drugs, I believe, will benefit, but we continue to see our growth, as Herve pointed out, coming from PV, GVHD and in myofibrosis were very stable and remain the market leader in that setting.

[David Lebowitz, analyst]

Would you be able to comment further on whether -- how growth in 2025 might look vis-a-vis 2024 given these dynamics?

[Barry Flannelly, executive]

No. We obviously said we're still confident about $3 billion plus by the time we hit 2028, so that's what we're still confident in. And so we think that '24 and '25 should be just fine.

[Operator]

Your next question is coming from Kripa Devarakonda from Truist.

[Srikripa Devarakonda, analyst]

On Jakafi, Herve, you mentioned that you see very little impact on Jakafi's share from competitors. Can you talk a little bit about whether the competition has changed the average duration on Jakafi? They do go on to Jakafi in the frontline, but is there any -- are you observing people getting off of Jakafi sooner? And also for the BET inhibitor combination, there was a recent report of increased AML incidents in patients on the Jakafi/BET combo for a competitor. I just wanted to get your insights into how this may or may not impact your internal BET program?

[Barry Flannelly, executive]

Kripa, I'll take your first call, and then I'll hand it over to Pablo for the second part of your question. So for Jakafi share from competitors. There really hasn't been any impact on our duration of therapy or discontinuation rates at all, certainly in myelofibrosis. So we're very confident. We remain the market leader. Other JAK inhibitors may be used in the second line, third line setting. If anything, the market size itself is growing because now patients will go on 1, 2, 3 therapies, and I'll hand it over to Pablo for the second part of your question.

[Pablo Cagnoni, executive]

Yes, thank you for the question. So I mean, obviously, I'm not going to comment on data from other companies. Our BET inhibitor program, as we've discussed, is going very well, and we'll discuss additional data over the course of the year, and we're planning a potential pivotal trial going forward, which we'll unveil later this year. Reviewing the data from our internal program, we have, at this point, no concerns over the safety when it comes to AML transformation.

Now you -- I'm sure you know that if you follow a number of patients with MF for long enough, some of them will have transformation to AML as part of the natural history of the disease. But at this point, we have no concerns with our program.

[Operator]

Next question is coming from Michael Schmidt from Guggenheim.

[Michael Schmidt, analyst]

I had a question on povorcitinib and again, commenting about another data set. But I just wanted to get your insight on the reasons RINVOQ head-to-head study against Dupixent and AD and whether or how that impacts perhaps your view on the potential of povorcitinib across various dermatology indications?

[Pablo Cagnoni, executive]

Yes, Michael, thank you for the question. Now we've seen the data. Obviously, it's an impressive data set. At this point, as you know, we have a number of studies ongoing with povorcitinib. We've had internal discussions about the potential to extending the trials of povo to atopic dermatitis. What I can say right now is we're encouraged by the data from RINVOQ. I think that it's an indication that povo could work very well in this disease. We have not made an internal decision that -- yet as to whether to develop povorcitinib in atopic dermatitis yet, but it's certainly something we're contemplating.

[Operator]

Your next question is coming from Marc Frahm from TD Cowen.

[Marc Frahm, analyst]

Maybe just start. One, just following up on the prior BET question. Can you -- were your comments just based on the clinical data you're seeing in those concern of AML? Or maybe can you speak to preclinically because I believe that BET inhibitor from a competitor has shown genotoxicity in some preclinical assays. Has yours shown genotoxicity?

[Steven Stein, executive]

Yes. It's Steven answering your question. So just to reiterate Pablo's remarks and remind you that our BET program was in the clinic a while ago in solid tumors. And then we've obviously pivoted to study myeloproliferative neoplasms. We've treated close to 200 patients to date. And in the clinical data set, which is the most powerful, as Pablo said, we have no concern as regards AML transformation or any concerns that we've seen in that regard. From a prior preclinical work on things like AIMS assay and genotoxicity, et cetera, we also have no issue, and we are aware of the issue with the competitor drug that was seen in preclinical work.

[Operator]

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

[Brian Abrahams, analyst]

I wanted to drill down a little bit more on the Jakafi dynamics. What's your explanation -- or I guess what do you think is the best explanation for the sequential downtick in total Jakafi demand? Was that something that's just seasonally related that you typically see in first quarter?

And then I guess, on the competitive front, I'm curious why you think you're not seeing any impact at this point to market share or patient persistence? Is this something you might expect to change going forward? Or would you expect market share and persistence to remain stable based on sort of what you're hearing in terms of market research and on the ground KOLs discussions?

[Herve Hoppenot, executive]

Maybe I can start on the uptick. I mean what we said, and you can see on the slide is that, in fact, there is an increase in the number of patients treated across all 3 indications in Q1 versus Q4, and there is a growth that you can see on the so-called paid-demand graph also that shows that versus last year there is a lot of growth in PV and GVHD.

So the unit growth of Jakafi sequential to Q4 and versus Q1 of last year is there and fairly visible. So reason for the sequential growth versus Q4 is what we discussed when we discussed Q4 a few months ago is that there was an abnormal free drug ratio in Q4 that has been completely fixed in Q1. So we are back to normal rates of free drug in Q1.

Now on the competitive side, maybe Barry, if you want to speak of why we don't see the impact of the new competitors.

[Barry Flannelly, executive]

Sure. I think, in fact, the new competitors, let's take [indiscernible] and momelotinib as examples, there -- as far as we can tell from all of our market research, from all of our experience working with hematologists, they're all being used in the second-line setting or maybe in patients that have very, very low platelets, for example. So we anticipate because of really the overall survival benefit of Jakafi, because of the tolerability of Jakafi, because of the symptom release of Jakafi, it's a great drug, and it will continue to be very useful to patients who have myelofibrosis going forward.

[Operator]

Next question today is coming from Vikram Purohit from Morgan Stanley.

[Vikram Purohit, analyst]

So we had 2, one on LIMBER and then one on Opzelura. So on LIMBER, were the ALK2 PoC data set we're expecting to see by the middle of the year, could you just frame for us kind of what the scope and size of the data set is going to be? And what you would define as sufficient for continued development for that program based on what we see for that PoC data set?

And then secondly, on Opzelura, I just wanted to revisit the topic of potential guidance and see when you think might be a good potential time to provide revenue guidance for Opzelura since you mentioned that it seems like the script shared seem stable between AD and vitiligo?

[Steven Stein, executive]

Vikram, it's Steven. So on your first question, just reminding of ALK2's mechanism felt to work through hepcidin inhibition and then ameliorate anemia by releasing iron and make it available for hemoglobin production. As we've already shown in multiple presentations, we can decrease subsiding levels. The question you get into, does this translate to some sort of clinical benefit? Just to remind you of the study, it has 3 groups, treatment group A, B and C. A was monotherapy, B was in combination with RUX, but those were in later-line patients. And the real focus right now, as you can see on clintrials.gov is treatment Group C, which is the treatment-naive group of patients to see in combination with RUX will help make an effect that will be of clinical benefit to patients, either by raising hemoglobin or preventing the decrease that sometimes occurs with JAK inhibition.

And then if we're able to demonstrate that as we dose increase in the second half of this year, then we'll have a clinical proof-of-concept that we can then potentially take forward to a regulatory environment, but we'll have to be clear that we are benefiting patients from a clinical benefit point of view in that treatment-naive group, and we'll have that data set second half of this year. I'll turn it over for the second question.

[Christiana Stamoulis, executive]

Vikram, it's Christiana. I'll take the second part. As we discussed on our last call, before we provide guidance for Opzelura, we are looking to have more real world data on utilization, especially for vitiligo. And data that goes beyond that first initial phase of therapy, which may represent a phase of experimentation by patients. So we are still early into the launch. We are still going through that initial phase of patients on therapy. So we're waiting for more real-world data before we are in a position to give you guidance.

[Operator]

Next question today is coming from Derek Archila from Wells Fargo.

[Derek Archila, analyst]

Just 2 quick ones from us. I guess, first, just on Jakafi. As you noted, the Jakafi growth coming from GVHD and PV. So I guess, what does this mean for future assumptions around myelofibrosis? I know you said stable, but how should we be thinking about that for the rest of this year?

And then in terms of CDK2, I guess, where do you think the bar is right now, I guess, from a PPP? And I guess what do you intend to show this year for proof-of-concept?

[Barry Flannelly, executive]

I'll take the first part of your question, it's Barry. So for Jakafi, we continue to see myofibrosis -- the way I look at the myelofibrosis patient population, there's about 18,000 patients, prevalent patients with myelofibrosis. And because we're the market leader, because of the overall survival and symptom benefit that Jakafi provides, we will continue to think of patients as either being on Jakafi, which is most of the myelofibrosis patients or they have been on Jakafi or they will be on Jakafi. When they progress on Jakafi, then there's other options, fortunately, that are available to them. But going forward for 2024 and beyond, we continue to expect to be the market leader in first-line myelofibrosis. And I'll turn the call over to Pablo.

[Pablo Cagnoni, executive]

Yes. Thank you for the question. So in our CDK2 inhibitor program, we continue to be encouraged by the data that we've seen. And regarding your part of your question about what data we're going to reveal later this year, we're in the final stages of optimizing the dose for the CDK2 inhibitor program. Our idea will be later this year to provide a substantial clinical data set, including the dose selection for patients. Initially, the focus will be ovarian cancer, but not necessarily only over the longer term as well as we are starting combination trials in ovarian cancer, and we're continuing to enroll patients with breast cancer.

So later this year, you will see the dose selection as well as the data for ovarian cancer as well as the development plan in ovarian cancer.

When it comes to the bar for efficacy, if you look at the CDK2 inhibitor landscape today, most of our competitors have decided to focus on breast cancer or other areas. We continue to believe that ovarian cancer is an important opportunity. Other competitors in the space like ADCs are coming into play. We're tracking those closely to figure it out what is the overlap between the different patient populations in different -- with different molecular markers. But basically, in the second part of the year, later this year, we'll provide clarity on dose, schedule and the development plan in ovarian cancer patients.

[Operator]

Next question today is coming from Jessica Fye from JPMorgan.

[Jessica Fye, analyst]

First, on Opzelura, is it possible to quantify the impact of the Change Healthcare issue for that product? And what about for Jakafi, was that impacted at all by the Change Healthcare issue in the quarter? And then on povorcitinib, the Phase III studies in vitiligo, I noticed on clinicaltrials.gov, it looks like there's a single primary endpoint of F-VASI75 for the Phase III trials, whereas RINVOQ, I think, has 2 primary endpoints of F-VASI75 and T-VASI50. So what's the rationale for only having a single primary endpoint here relative to the competition? And how do you expect that to kind of play out based on the end points you're studying?

[Matteo Trotta, executive]

Thank you, Jessica. I'll take the Change Healthcare on Opzelura. What we see at the end of February that there was this cyber-attack reported pretty much caused the network interruption for a few weeks. So as a result, the Change Healthcare was unable to process the claim for a few weeks. When we looked at -- when we deep dive in the data, we saw a softer March when you look at the entire atopic dermatitis market basket that we monitor, and that caused an estimate of $4 million to $5 million negative impact from Opzelura in Q1. The good news for us is that we're monitoring April, and we see demand, weekly demand back on track to the levels we saw pre-cyber-attack and the more recently.

[Barry Flannelly, executive]

And Jessica, just on Jakafi, we may have actually had an impact from Change Health, but we don't know. We did have when it first happened some request from specialty pharmacies that wanted extended terms for payment. But we really can't see a big impact because most of the specialty pharmacies were able to switch over to the other system that provides the service for the specialty pharmacies.

[Steven Stein, executive]

And then just to address your question on povorcitinib in vitiligo, we have 2 identical Phase III studies ongoing STOP-V1 and STOP-V2 in patients 18 years or older with 5% or greater body surface area involvement of non-segmental vitiligo. It's a little tricky on the endpoints. But just to tell you, our primary end point for the FDA in the United States is actually identical. It's facial-VASI75 and Total VASI50. For other parts of the world, there may be a different primary endpoint. For example, in Europe, they're interested most in the Total-VASI50. So that leads to some of the confusion. But for our study, for the FDA, it's both Facial-VASI75 and Total-VASI50, together measured at week 52.

[Operator]

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

[Tazeen Ahmad, analyst]

On Opzelura, can you -- and I'm sorry if I missed this in your prepared remarks, but can you talk about refill rates for patients maybe now that have been on therapy for a few quarters? Can you talk about how you're seeing their use of tubes? What's the average use of tubes is? I'm just curious that if patients are having good results with the cream, whether they're taking many drug holidays in between when they don't have as much itch, for example?

[Herve Hoppenot, executive]

Yes. Matteo, can add to the comment. I mean the picture in terms of refill rate has been the following, is that -- in atopic dermatitis, we have observed a refill that is slightly north of 2 tubes per patient. And that's relatively stable. Now it's still increasing a little bit, but it is relatively stable.

In vitiligo, it's moving very quickly, and we are not yet at the steady state. It is a situation where we see, unfortunately, that there are patients who are not complying with the treatment as it was prescribed, and we are obviously working with physicians and patients directly to improve it.

And as you know, I mean from the experience we had in the clinical trial, we are estimating that if we are successful, it will be around 10 tube per patient, but we are still at the number that is lower than that today when you try to look at patients who have enough history. So do you want to speak about what we are doing on the marketing side.

[Matteo Trotta, executive]

Yes. The only comment that I can add is on -- just in this quarter, we're launching a very promising adherence program that we we're confident will impact -- will continue to impact the refill rate growth that we see across both indications, AD and Vitiligo.

[Operator]

Next question today is coming from Salveen Richter from Goldman Sachs.

[Salveen Richter, analyst]

Could you just give us an update on how the ex U.S. launch of Opzelura is progressing with the addition of France at this point? And how you're thinking about the pediatric uptake in 2025? And if I could also just ask 1 on business development. Post the recent acquisition, you still have significant balance sheet capacity. Could we see you do meaningful M&A in the near term on top of Escient?

[Herve Hoppenot, executive]

Okay. So maybe starting, I'll take the first part about the European launch because, in fact, there is a lot of activities going on there. As you know, we launched in Germany and Austria. So that's the base that we have. Recently, we are part of Accès Direct, which is a French process where you can commercialize your product while you are negotiating the price. So what you see in the numbers today is that there are around $2 million that are recognized sales from France. And it's a sort of an estimate with a conservative price per tube that we are using to do that. But the process there is moving very well, and we anticipate by the second half of the year to be fully reimbursed and paid for at a good price in France.

And we have now in Italy and Spain agreement on the price where we will be launching between midyear and the second half of the year in both countries. So Germany, Italy, Spain and France will be fully operational by Q3 and will be contributing to the top line. There is also some smaller countries in Europe where the process is ongoing, and there is always the big question mark of the United Kingdom, England, where, as you know, the pricing discussion can take more time, and we are in the process there.

So it's a very positive outcome for Opzelura in Europe because we got reimbursement now in many countries and most of the large countries. And we see a very good uptake of the demand in terms of volume in the countries where it's available, specifically in France.

Now the second part of your question was about the pediatric uptake in the U.S. when we get approval. So maybe, Matteo, if you want to speak about that?

[Matteo Trotta, executive]

Yes, sure. Thanks for the question. And we're very excited by the potential opportunity to help 2 million, 3 million children in the U.S. And we see data consistent with what we would expect. So pending FDA approval, we are excited by another contribution and tailwind to our top line. This is a patient population that maybe the parents will be a little more sensitive to our box warning, but at the same time, it's 2 million, 3 million patients and children that we potentially have the opportunity to help going forward.

[Herve Hoppenot, executive]

On the business side, maybe, Christiana, you can...

[Christiana Stamoulis, executive]

Yes. Sure. So Salveen, as you commented on, we have a strong balance sheet, and we'll continue to have a strong balance sheet following the Escient acquisition. So as of the end of this quarter, we have $3.9 billion of cash. We don't have any debt, which obviously that could give us additional firepower. So that puts us in a position to be able to look at additional opportunities. And that's something that we are continuing to explore.

[Operator]

Our next question today is coming from Eric Schmidt from Cantor Fitzgerald.

[Eric Schmidt, analyst]

Maybe just following on Salveen's question on capital redeployment. Can you talk about your broader strategy there about also whether you consider returning cash to shareholders in the form of a dividend or a share buyback in addition to potentially using cash to expand your business?

[Herve Hoppenot, executive]

I can take that. I mean it's -- we have been speaking about acquisition and external opportunities, which is obviously one very clear goal for the corporation is to diversify our revenue in the future and to increase to the growth coming from the current portfolio that we have. So that's one option. And obviously, as we are doing with our Board, there are discussions about alternatives to that. But today, as you have seen with Escient, I mean, there are opportunities that are very much in the range of what we are looking for in terms of timing and in terms of therapeutic areas, and that would be of an interest. So we are basically looking at both.

[Operator]

Next question is coming from Jay Olson from Oppenheimer.

[Jay Olson, analyst]

Congrats on the progress of your KRASG12D. It seems like Incyte is increasingly focused on targeted oncology versus immuno-oncology. Can you describe your strategy in oncology? And Also, how are you planning to leverage your oral PD-L1 for your targeted oncology programs, in combination with your KRASG12D, or do you plan to develop additional KRAS inhibitors?

[Pablo Cagnoni, executive]

Yes. So thank you for the question. So your observation is correct. We are moving more aggressively into targeted oncology and trying to shift away from immuno-oncology. And that's a journey that has started a little bit over a year ago, and we intend to accelerate in the future. The idea here is well-defined patient populations, large treatment effect ideally single-agent activity with early proof-of-concept, and that will allow us to have much more efficient drug development process to accelerate some of these programs.

We're very excited about the G12D program. We think it has the potential to be best-in-class. And as you point out, one of the things that we can leverage is we have access to what we believe is the most advanced for sure, oral PD-L1 inhibitor, and that will allow us to do oral-oral combinations in patients with a range of indications. And that applies also to the rest of the pipeline. And as I mentioned, that journey will continue to accelerate in the future.

[Operator]

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

[Matthew Phipps, analyst]

I guess I'll ask about the CALR-mutant antibody and data in early 2025, will that be monotherapy or mono and Jakafi combo and also myelofibrosis only or also including essential thrombocytopenia? And I guess just from a high level, the combination with Jakafi, is that primarily to provide faster symptom relief? Or do you think it is just kind of necessary to achieve efficacy for the antibody?

[Pablo Cagnoni, executive]

So we haven't decided exactly the scope of the data disclosure for the mutant-CALR antibody later this year. What I can tell you is that plan is to combine the mutant-CALR antibody with Jakafi. And the idea there is, as you know, and we pointed out many times, Jakafi has a profound effect on symptom relief in these patients, which we believe, early in the management of the disease, could be very important even in the presence of a mutant-CALR antibody. The idea of mutant-CALR antibody here, as you know, is to transform -- is to change the treatment objective to really eradicate the malignant clone. But still a potential early treatment or induction with Jakafi could be very, very helpful for patients.

And regarding the other part of your question. Yes, we will have data in MF and ET as well.

[Operator]

Our next question is coming from Evan Seigerman from BMO Capital Markets.

[Evan Seigerman, analyst]

Two from me. One, just taking a step back looking at P&L management. How do you think about being most efficient with your OpEx? And then kind of a follow-up there. Would you ever consider using some of your balance sheet to, say, do buybacks, especially with the stock in the [ $50s? ]

And then just as you think about your positioning in the derm space, a lot of focus on Opzelura. Where do you want to win over the next 5 years when it comes to derm? Where do you think Incyte is best suited to really take share? Maybe you can walk me through some of the most exciting parts of your pipeline in your view.

[Herve Hoppenot, executive]

Okay. So I think the first question was about the efficiency of the spending. So as you see, I mean, we have in our P&L, we had a relatively -- this quarter, we had a very flat SG&A and a relatively slower growing R&D. And that's what we have been speaking about for years now is basically growing the top line at a faster rate than we are growing both components of the expenses and increasing leverage. So that's sort of happening. They are depending on the event on the quarterly, it's not always at the same rate, but it's clearly the direction that we are taking.

Concerning the buyback, I spoke about it. What I'm basically saying is that nothing is excluded from discussions, and that's something that is certainly part of the current dialogue. And now in the dermatology, maybe, Pablo, if you want to speak about, or Steven, on the...

[Pablo Cagnoni, executive]

I'm happy to comment. Look, I think what we're building is an important portfolio of first-in-class or best-in-class in some cases, best-in-disease medicines in the - I would expand the questions in the inflammation space.

And I think that was a key driver of the acquisition of Escient to complement that with 2 first-in-class medicines, 262 and 547, that can really address a range of indications. We believe that, that added to the portfolio that we have with povorcitinib, which is [indiscernible] pipeline within a drug, we can win across a range of indications by providing patients and payers with a portfolio approach to some of these diseases, including prurigo nodularis, atopic dermatitis and now the new inflammatory diseases.

[Operator]

Your next question is coming from Reni Benjamin from Citizens JMP.

[Reni Benjamin, analyst]

Just a couple of quick ones. One on Jakafi XR. Can you provide any sort of an update as to how that's progressing? And as you think about the strategy going forward, is this something that you're already starting to evaluate in combinations? Or do you only start doing that after an approval?

And then just as a follow-up, tafasitamab, just wanted to get your thoughts on the FL, MCL data that's coming out. Is this is really going to be meaningful from a commercial perspective versus the real opportunity in first-line DLBCL, which is expected in 2025?

[Steven Stein, executive]

So Ren, it's Steven answering your question. So as Pablo said in remarks earlier this year, the XR process is underway with the regulators in terms of doing bioavailability and then followed by BE work. That will include stability. So it's about a 2-year process, which we expect to complete in a way in time for the LOE. And the idea there is obviously to have the once daily available in time. It doesn't change any of our FDC work. We can still do fixed-dose combination work with BET and ALKs. We need to do, and we continue to progress those.

In terms of tafasitamab, the studies are complete, both in mind and front mind. So the low-grade follicular and marginal zone lymphoma study will be in the second half of this year. And in the first-line diffuse large B-cell lymphoma probably in Q1 2025. And we await that data. We know we have an active -- very active and well-tolerated regimen in lymphomas, and we look forward to that data.

As someone also brought up earlier there, and Pablo said, there's also interest now potentially in autoimmune work with CD19 antibodies, and that's something we're just looking at, at the moment.

To the meat of your question, yes, we very much expect the data to be meaningful with a well-tolerated active regimen, and we look forward to those data sets.

[Operator]

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

[Gavin Clark-Gartner, analyst]

Just wanted to ask one quick clarification on the CALR data. Did you note that you're planning to show some of that data later this year? Or could that still be a 2025 event?

[Pablo Cagnoni, executive]

We haven't provided specific guidance. I think we said 2025. So if I imply 2024, I apologize for misunderstanding but it's -- 2025 is the goal.

[Operator]

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.

[Ben Strain, executive]

Thank you all for participating in the call today and for your questions. The IR team will be available for questions throughout the day. Thank you and goodbye.

[Operator]

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.