Incyte (NASDAQ:INCY) Corporation (NASDAQ: INCY) reported strong financial results in its third-quarter 2024 earnings call, with total revenues reaching $1.14 billion, marking a 24% increase year-over-year. The company's net product revenues stood at $963 million, driven by the success of its flagship products Jakafi and Opzelura. Incyte is preparing for several significant product launches and anticipates substantial revenue contributions from its diversified pipeline by 2029.
Key Takeaways
- Incyte's total revenues for Q3 2024 increased by 24% year-over-year to $1.14 billion, with net product revenues of $963 million.
- Jakafi's net revenues were $731 million, a 16% increase, while Opzelura rose by 52% to $139 million.
- The company raised its 2024 revenue guidance to between $2.74 billion and $2.77 billion.
- R&D expenses reached $573 million, including a $100 million milestone payment to MacroGenics (NASDAQ:MGNX).
- Incyte expects significant revenue contributions from Niktimvo, tafasitamab, and retifanlimab by 2029.
- The company has a strong pipeline with multiple pivotal studies reporting results in early 2025.
Company Outlook
- Incyte projects robust operational growth moving into 2025, with a strong emphasis on its pipeline.
- The raised revenue guidance reflects confidence in the company's commercial performance and product launches.
- Incyte is preparing for the U.S. launch of Niktimvo in Q1 2025 and aims for approval of ruxolitinib cream in pediatric atopic dermatitis in H2 2025.
Bearish Highlights
- The company will not advance certain indications into registrational studies at this time.
- Concerns were raised about the efficacy of the ALK program during the Q&A session.
Bullish Highlights
- Positive top-line results from the Phase 3 study of tafasitamab for follicular lymphoma, with an sNDA filing expected this year.
- The pivotal Phase 3 study of retifanlimab in SCAC showed a 37% reduction in risk of progression or death.
Misses
- No specific misses were highlighted in the summary provided.
Q&A Highlights
- Questions about the ALK program's efficacy and the CDK2 program's plans for registrational studies were discussed.
- The potential market for RUX cream and povo in treating Hidradenitis Suppurativa (HS) was addressed, with a 2026 approval timeline projected.
Incyte's pipeline continues to show promise with updates on ruxolitinib cream and povorcitinib, and the company is advancing its BET inhibitor program into Phase 3 development. The company's clinical trials, including those for compounds 262 and 547, are progressing, with data expected in Q1 2025. Incyte also highlighted the growth of Jakafi in the myelofibrosis market and ongoing trials measuring tryptase levels for drug 262.
The company's strategic approach to sales and marketing is reflected in its U.S. sales force of around 200 members, which is deemed sufficient for upcoming product launches. Incyte remains optimistic about its pipeline, with anticipation for data releases at the ASH conference later in the year and multiple catalysts expected to contribute to top-line growth.
Incyte's advancements in oncology include the development of a CDK2 inhibitor for ovarian and potentially endometrial cancer, with over 200 patients treated showing promising efficacy and a manageable safety profile. The company is preparing for registrational studies in 2024 and aims for a differentiated position in the market through a maintenance study in combination with bevacizumab.
The company concluded the call by expressing gratitude for participation and inviting follow-up questions, signaling openness to continued dialogue with investors and analysts. With its diversified pipeline and strategic sales approach, Incyte is positioned for robust growth while navigating competitive landscapes in oncology and dermatology.
InvestingPro Insights
Incyte Corporation's strong financial performance in Q3 2024 is reflected in its market valuation and recent stock performance. According to InvestingPro data, Incyte boasts a market capitalization of $14.22 billion, indicating significant investor confidence in the company's future prospects. This aligns with the company's reported revenue growth and raised guidance for 2024.
The company's revenue growth is particularly noteworthy, with InvestingPro data showing a 12.94% increase in the last twelve months as of Q3 2024, and an even more impressive 23.81% quarterly growth. This robust growth trajectory supports Incyte's optimistic outlook and expectations for substantial revenue contributions from its pipeline by 2029.
InvestingPro Tips highlight that Incyte holds more cash than debt on its balance sheet, which is a positive indicator of the company's financial health and ability to fund its ambitious R&D programs and product launches. This strong financial position is crucial as Incyte prepares for several significant product launches and continues to invest heavily in its pipeline.
Another InvestingPro Tip notes that management has been aggressively buying back shares, which often signals confidence in the company's future performance and can be seen as a positive sign for investors. This aligns with the company's bullish outlook and expectations for operational growth moving into 2025.
It's worth noting that Incyte's stock has seen a significant return over the last week, with InvestingPro data showing a 12.94% price total return. This recent uptick could be attributed to the positive Q3 results and raised revenue guidance.
For investors seeking a more comprehensive analysis, InvestingPro offers 14 additional tips for Incyte, providing a deeper understanding of the company's financial health and market position.
Full transcript - Incyte Corporation (INCY) Q3 2024:
Operator: Greetings, and welcome to the Incyte Third Quarter Financial Results 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 Ben Strain, Associate Vice President, Investor Relations. Please go ahead, Ben.
Ben Strain: Thank you, Kevin. Good morning, and welcome to Incyte's third quarter 2024 earnings conference call. Before we begin, I encourage everyone to go to the Investor section of our website to find the press release, related financial tables and slides that follow today's discussion. On today's call, I'm joined by Herve, Pablo, Christiana, who will deliver our prepared remarks. Barry, Matteo and Steven will also be available for Q&A. I would like to point out that we'll be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. I will now hand the call over to Herve.
Herve Hoppenot: Thank you, Ben, and good morning, everyone. The third quarter of 2024 was a very positive quarter for Incyte with a good commercial performance, FDA approval of Niktimvo and progress of our pipeline with several key data readouts for our clinical programs. In Q3, total revenues increased by 24% year-over-year to $1.1 billion, with net product revenues growing 23%. This growth was driven by the ongoing demand growth for Jakafi and Opzelura, which I will highlight in the following slides. In August, we, along with our partner, Syndax, announced the FDA approval of Niktimvo for patients with chronic graft-versus-host disease after failure of 2 prior lines of therapy, making it the first anti-CSF-1R approved to target the inflammation and fibrosis associated with chronic GVHD. To facilitate patient dosing and limit product waste following the FDA's approval of Niktimvo, we have submitted 2 smaller vial sizes to the FDA for the approval. Following the potential approval of the new vial sizes, we anticipate launching Niktimvo in the U.S. in the first quarter of 2025. Additionally, the positive pivotal AGAVE-201 trial results were recently published in the New England Journal of Medicine. Niktimvo was also included in the latest NCCN Clinical Practice Guidelines in Oncology for chronic GVHD treatment, both highlighting the significance of this dataset and the transformative potential of Niktimvo. The sNDA for ruxolitinib cream in pediatric atopic dermatitis was recently filed with the FDA, and we are on-track for a potential approval in the second half of 2025. During the quarter, we also provided important clinical updates at ESMO with encouraging data for our CDK2 inhibitor in ovarian and endometrial cancer as well as data from the Phase 3 trial of retifanlimab in SCAC. At [indiscernible], we presented extensive data on both povorcitinib and ruxolitinib cream, including multiple lead breaking presentations that showed the potential of this program to enhance treatment options for individuals with immune mediated dermatologic conditions such as vitiligo, atopic dermatitis, hidradenitis suppurativa and prurigo nodularis. Moving to Slide 6 and an update of the third quarter commercial performance of Jakafi. Jakafi net product revenue were $731 million, up 16% year-over-year, paid demand increased 10%, driven by patient growth across all indications. Based on the strength in demand seen during the first 3 quarters of 2024, we are raising our full year 2024 Jakafi net revenue guidance to a new range of $2.74 billion to $2.77 billion. Turning to Slide 7 and looking at Jakafi total paid demand by indication during the first 9 months of 2022, '23 and '24. As you can see, unit growth remains robust. Myelofibrosis is stable year-over-year with some modest growth seen again this quarter, while the most significant growth is seen in polycythemia vera and graft-versus-host disease. We expect PV to become the largest contributor for Jakafi over time, supported by the data from the MAJIC PV study, which underscores the benefit of early intervention with Jakafi and its impact on thrombosis free survival. Moving to Opzelura on Slide 8. Total Opzelura net product revenues in the third quarter were $139 million, up 52% when compared to the same quarter last year. In the U.S., the annual prescription trends for 2022 and '23 and year-to-date '24, as shown on the right of the Slide 8, reflects continued year-over-year growth of Opzelura from both atopic dermatitis and vitiligo. During the third quarter, we continued to progress with the launch of Opzelura in Europe to $20 million in net sales during the third quarter were driven by France, where Opzelura is now reimbursed and available in retail pharmacy and from Germany. Earlier this month, we also achieved approval for atopic dermatitis and vitiligo in Canada. On Slide 9, I want to highlight 3 products that are expected to begin contributing to revenue in the near-term. We anticipate that Niktimvo for third-line chronic GVHD, tafasitamab for follicular lymphoma and retifanlimab for SCAC could collectively generate $800 million or more in incremental revenues by 2029. We anticipate all 3 products to be available in 2025 and this incremental sales will be leveraging the current commercial infrastructure used for Monjuvi, Pemazyre and Jakafi. As illustrated on Slide 10, these 3 launches anticipated in 2025 will be followed by larger opportunities in 2026 and 2027, including povorcitinib CDK2 and tafasitamab in first-line DLBCL. Between 2027 and 2030, we have multiple programs that hold transformative potential with data for each anticipated in 2025. I will now turn the call over to Pablo.
Pablo Cagnoni: Thank you, Herve, and good morning. As we continue to execute on our pipeline of numerous potential first or best-in-class medicines, we remain on track to deliver more than 10 high-impact launches by 2030. In the next few slides, I will highlight a number of these programs. We continue to expand the opportunity of ruxolitinib cream with additional indications. Based on the positive Phase 3 data in pediatric atopic dermatitis, the supplemental NDA was recently filed. With the potential approval in 2025, we are excited with the possibility of providing an effective nonsteroidal topical options for the 2 million to 3 million pediatric patients with AD in the U.S. Following interactions with the FDA, we have finalized the design for the Phase 3 study of ruxolitinib cream in patients with mild to moderate hidradenitis suppurativa. The study, which will have a primary implant of high-score 75 is expected to begin in the first half of 2025 and could represent a new treatment option to the approximately 150,000 patients with mild to moderate HS in the U.S. As a reminder, we're currently conducting a Phase 3 study evaluating ruxolitinib cream in patients with prurigo nodularis, a chronic skin disorder that presents its multiple firm nodules, commonly located on the extensive surfaces of the extremities and that are intensely predict. This pivotal study is enrolling well, and we are now on track to report results in the first half of 2025 with a potential approval as early as 2026. With no topical therapies currently approved for PN and approximately 200,000 patients diagnosed in the U.S., we see this as an important additional option for patients and a significant opportunity for ruxolitinib cream. As shown on Slide 15, we're continuing to execute a broad development plan for povorcitinib, our oral small molecule, highly selective JAK1 inhibitor. Povorcitinib is currently being evaluated in Phase 3 studies in hidradenitis suppurativa, vitiligo and prurigo nodularis and in randomized Phase 2 proof-of-concept studies in asthma and chronic spontaneous urticaria with data for both expected in 2025. Povorcitinib has already shown encouraging efficacy and safety in a randomized Phase 2 study involving patients with moderate to severe hidradenitis suppurativa, a highly painful inflammatory condition. As a reminder, we reported that by week 52, up to 29% of patients achieved a HiSCR 100 response, indicating complete resolution of all symptoms. Additionally, povorcitinib demonstrated a rapid and significant reduction in pain, offering the opportunity to transform the current standard of care for this disease. The 2 Phase 3studies, STOP-HS1 and STOP-HS2, are enrolling well, thanks to the strong Phase 2 data and the limited effective treatment options available. We expect to have Phase 3 data by early 2025. We have refined our guidance for the Phase 2proof-of-concept study of povorcitinib in chronic spontaneous urticaria and now anticipate data in the first half of 2025. CSU is a mast cell-driven disease characterized by hives and severe chronic itching. The overactivation of dermal mast cells and basophils leads to increased serum levels of Th1, Th2 and Th17-related cytokines. We know that JAK1 inhibition can modulate mast cell activation, including the granulation and cytokine production, both of which contribute to chronic spontaneous urticaria. This randomized double-blind Phase 2 study is being conducted in patients who are inadequately controlled or have progressed on second-generation antihistamine, which represent a potential patient population of over 300,000 patients in the U.S. alone. As you can see on Slide 16, our updated inflammation and immunity pipeline continues to evolve. Recently, we presented promising data from a Phase 2 study of ruxolitinib cream in patients with cutaneous lichen planus. At this time, we do not plan to advance ruxolitinib cream into a registrational study for the syndication and intend to publish the results of the study in the future. For lichen sclerosus, given the prioritization of other indications and programs, we are not currently planning to advance this indication into a registrational study. As a reminder, 262 and 547 are currently being evaluated in a number of indications, and we anticipate data for these studies in the first quarter of 2025. Moving to MPNs and graft-versus-host disease on Slide 17. We highlight here a number of ongoing programs where we have the goal of developing new therapeutic options to build upon the significant impact Jakafi has had on patients. Our BET inhibitor dose escalation is ongoing, both as monotherapy and in combination with ruxolitinib. As a reminder, we have reported reductions in spleen length in volume as well as improvements in both symptoms and hemoglobin. We plan to advance this program into Phase 3 development and expect to provide an update later this year. Additionally, for zilurgisertib, our ALK2 inhibitor, we plan to provide an update later this year. And for ruxolitinib XR, we plan to share the Bioequivalence data in early 2025. Moving to our oncology pipeline on Slide 18. We continue to build a robust portfolio with increased emphasis on first-in-class and our best-in-class and novel immuno-oncology programs. For tafasitamab, we shared positive top line results from the Phase 3 study in patients with follicular lymphoma and we are on track to file the sNDA with the FDA this year, which could lead to a potential approval in 2025. As a reminder, the Phase 3 data for first-line DLBCL in combination with R-CHOP is expected in the first half of 2025. During the ESMO conference in September, we shared positive top line results for the pivotal Phase 3 study of retifanlimab in SCAC. Retifanlimab met the primary endpoint, demonstrating a clinically meaningful 37% reduction in the risk of progression or death with a hazard ratio of 0.63. The study showed that retifanlimab was generally well tolerated and no new safety signals were detected. At ESMO, we also shared promising evidence of clinical activity from our potentially first-in-class small molecule CDK2 inhibitor, which demonstrated a number of complete and partial responses as well as stable disease in patients with Cyclin E1 overexpressing tumors, most notably in ovarian and endometrial cancer. We believe our CDK2 inhibitor could be a foundational therapy for patients with ovarian cancer as well as other Cyclin E1 overexpressing tumor types, and we plan to move aggressively in initiating registrational studies in 2025. We will be meeting with FDA in the coming months to discuss trial designs. As highlighted on the slide, we're considering different designs for the registrational program, and we will continue to update you on the regulatory strategy for this program in the coming months. In closing, Slide 20 shows a summary of the considerable number of milestones across the remainder of 2024 and 2025. These milestones will continue the transformation of our pipeline with a strong focus or new molecular entities with the potential to make an indelible impact on patients. With that, I would like to turn the call over to Christiana for the financial update.
Christiana Stamoulis: Thank you, Pablo, and good morning, everyone. Our third quarter results reflect strong commercial execution and continued growth with total revenues of $1.14 billion, up 24% versus the same period last year. Total product revenues of $963 million in Q3 were driven by strong demand growth for Jakafi and Opzelura and increased revenue contribution from Monjuvi as a result of the acquisition of food rights to tafasitamab earlier this year. Total royalty revenues were $157 million, up 20% compared to the third quarter of 2023, driven by increased demand for Jakavi and Olumiant. Turning to Jakafi on Slide 24. Jakafi net product revenues were $741 million for the third quarter, reflecting continued demand growth with total demand up 10% year-over-year, driven by growth in all indications and a $9 million gross to net favorability as a result of through ups to prior quarter estimates. At the end of Q3, channel inventory was up 2% year-over-year and stable quarter-over-quarter and within normal range. Turning now to Opzelura on Slide 25. Net product revenues for the third quarter were $139 million, representing a 52% year-over-year increase driven by growth in new patient starts and refills across both AD and vitiligo in the U.S. as well as continued contribution from the commercialization of Opzelura for vitiligo in Europe. In the third quarter, Europe contributed $20 million of Opzelura net product revenues, driven by continued uptake in Germany and broader access in France where Opzelura is now reimbursed and available in retail pharmacies. Third quarter net product revenues in France include a $2 million stock build up at wholesalers. Finally, in the third quarter, we made significant progress in including Opzelura on regional formularies in Spain and Italy. Moving on to Slide 26 and our operating expenses. Total GAAP R&D expenses were $573 million for the third quarter due to the $100 million milestone payment made to MacroGenics during the quarter and continued investment in our late-stage development assets. Excluding all onetime expenses, ongoing R&D expenses for the third quarter increased 26% compared to the same period in '23 due to continued investment in our late-stage development assets, additional R&D expenses resulting from the Escient acquisition and timing of certain expenses. For the 9-months ended September 30, 2024, ongoing R&D expenses increased 15% compared to the prior year period as a result of increased investment in the Phase 3 studies of povorcitinib and Opzelura. As we wrap up the clinical development of axatilimab in third-line chronic GVHD, tafasitamab in relapsed refractory follicular lymphoma and retifanlimab in SCAC and non-small cell lung cancer as well as the development activities of discontinued programs, we anticipate the reduction in investment in those programs to partially offset the increased investment in other programs, which would allow us to control future R&D expense growth. Moving to SG&A. Total GAAP SG&A expenses were $309 million for the third quarter, representing a 15% year-over-year increase primarily driven by timing of consumer marketing activities and certain other expenses. For the 9 months ended September 30, total GAAP SG&A expenses increased 6% year-over-year. Finally, total ongoing operating expenses for the first 9 months of the year increased 11% versus a 14% increase in revenues, leading to an increase in operating leverage and margins. Moving on to our guidance for 2024. Based on the strong performance of Jakafi in the first 9 months of the year, we are increasing our full year 2024 guidance to a new range of $2.74 billion to $2.77 billion. We are also updating our full year guidance for other hematology/oncology products to a new range of $310 million to $320 million to reflect the first 9 months actual demand and the unfavorable impact of foreign exchange rates. In addition, we are updating the full year GAAP R&D guidance to include the $100 million milestone payment to MacroGenics. The full year GAAP R&D guidance is now $2.54 billion to $2.59 billion, which includes $791 million in onetime expenses related to the $691 million of upfront consideration for the acquisition of Escient and the $100 million milestone payment to MacroGenics. Ongoing R&D guidance remains unchanged. Finally, we are reiterating our full year 2024 guidance for COGS and SG&A. Operator that concludes our prepared remarks. Please give your instructions and open the call to Q&A.
Operator: [Operator Instructions] Our first question today is coming from Michael Schmidt from Guggenheim.
Michael Schmidt: Congrats on a great third quarter. I had one on povorcitinib. Just looking ahead to the upcoming Phase 3 data in hidradenitis early next year. So beyond top line success, do you have any thoughts on where you think -- where you want efficacy to shake out in order to be competitive with Humira and other market biologics? Is there a particular placebo-adjusted effect size that you're looking for to hit with povorcitinib?
Steven Stein: Michael, it's Steven. Just taking your question. And thank you for the question on HS. Our feeling is if we replicate the Phase 2 data, which was incredibly strong, and as Pablo said in his prepared remarks, that includes HiSCR 100 of up to 29%, then we'll have an extremely favorable efficacy profile that will really benefit patients with HS. You couple that with the other symptomatology, particularly the pain from the lesions, and we were able to get in that Phase II data set to demonstrate pain relief, and that will add to what we think will be a differentiated profile that will really benefit patients. Obviously, it's hard to predict how Phase 3 will read out. The other thing Pablo alluded to in his prepared remarks is extremely good enrollment on both studies, which is probably a testament to the Phase II data driving investigators wanting to put patients on the study.
Operator: Next question is coming from Jessica Fye from JPMorgan.
Jessica Fye: I had a few on the pipeline. I believe earlier this morning, Novartis (SIX:NOVN) announced the longer follow-up time is needed to determine the regulatory path forward for their BET inhibitor. Curious how that impacts at all your thinking or development strategy for your BET? And then can you help us think about the potential development plans for povorcitinib and 262 in CSU? And just kind of where you see both molecules best fitting in the treatment paradigm?
Pablo Cagnoni: Yes. Jess, this is Pablo. Let me take the first one. So our BET inhibitor, as we presented over the past year, and we will provide an update later this year, we're very happy with the data that we've seen so far. We've seen spleen reduction to volume reduction. We've seen a pretty impressive improvement in symptoms, obviously, with the caveat that this is not randomized blinded data, but very important effect on symptoms. We believe that the ability of our BET inhibitor to be dosed continuously as opposed to the way pelabresib has to be dosed with a break of a week every 2 weeks could potentially make it an important difference in our ability to control symptoms. So our plan remains the same. As I said in my prepared remarks, we'll provide an update on the data before the end of the year and we intend to advance into a Phase 3 study, and we will provide details on those designs when we provide an update on the data. So that plan remains the same. On povo 262 for CSU, both are in different stages in a way. Povo, as you know, is in a randomized Phase 2 study for proof of concept. We believe there's a potential for povo in this indication because of the very strong anti-inflammatory effect that it has. So we look forward to sharing data and future plans after that. 262 is in a randomized Phase 2 study with 2 dose levels at 50 and 150 compared with placebo. And we also initiated a study or a lower dose of 25 milligrams compared with placebo. And the idea here is to explore a full range of doses for 262 to potentially once we have the results, assuming positive results to be ready for pivotal studies. In terms of how both fit, I think the difference here is probably a sequence on how these medicines could potentially be used in patients with SCAC. As you know, first line of therapy antihistamines, about 50% to 60% of the patients do not respond into antihistamine or progress on antihistamine. This is a multiyear disease. And so patients need a sequence of treatment to be used to see which one controls best the symptoms for that particular individual. The mechanism is different. Povorcitinib has a broad inflammatory effect. 262 is exquisitely designed to block MRGPRX2 in mast cells in the skin. So we believe that, that selectivity will lead to an excellent safety profile. So once we have data for both programs, we'll share a little bit more on how we think those can potentially be sequenced in the treatment paradigm.
Operator: Next question today is coming from Salveen Richter from Goldman Sachs.
Salveen Richter: Just regarding the Escient portfolio. Could you just help us understand how you're thinking about development strategy here when you think about the different mechanisms addressing some of these diseases and how you see the differentiation playing out?
Steven Stein: Yes. So we have 2 programs that were acquired with Escient MRGPRX2 and MRGPRX4. So MRGPRX2 is currently being developed in 3 indications. Chronic spontaneous urticaria. And I just highlighted where we are with that indication. We have an ongoing study with 2 dose levels versus placebo, 50 and 150 and the second study of 25 milligrams versus placebo. Once we have all that data, we'll decide next steps for chronic spontaneous urticaria. For the other 2 indications are chronic inducible urticaria, particularly focused on 2 of those, dermographism and cold-induced urticaria and atopic dermatitis. The reason why we like MRGPRX2 as a target is the excellent selectivity, not just for cell type, mast cells, but also mast cells specifically in the skin and connective tissues. And we think that should lead to an excellent safety profile and make this, perhaps, in some of these patients, the first therapy after patients progress on antihistamines in the case of urticaria, chronic urticaria, for example. So good evidence of efficacy. Together with a very, very clean safety, we think it will make this a very important option for patients at that stage of the disease. The second program was MRGPRX4. This has been developed in patients with cholestatic pruritus, specifically primary biliary cirrhosis and primary cirrhosis cholangitis. We know that X4 is a receptor, bile acids and bile salts bind to it, and this is an important way in why these patients have intractable pruritus. We are conducting a randomized double-blind study in those indications. We'll have data in the first quarter of 2025, same as for MRGPRX2 program. And once we report all the data early next year, we'll give you clarity on the next steps.
Operator: Our next question is coming from Eric Schmidt from Cantor Fitzgerald.
Eric Schmidt: Congrats again on all the updates. Maybe a commercial question for Matteo on Opzelura and the potential upcoming launch for pediatric AD in the second half of next year. How do you think you're doing with regard to formulary access and efforts to ensure reimbursement and what could be a pretty sizable marketplace?
Matteo Trotta: Yes. Thanks, Eric, for the question. On the pediatric side, we're very excited about the potential for us to bring this new tool to patients 2 and 11 years old in AD. The unmet need is very clearly there. We have 2 million patients in terms of sizing. They're still cycling vastly on TCS and TCIs, and there still remain a high unmet need for us to potentially get into that. In terms of the 2025 formulary coverage, I mean, we look at the formulary position for the entire Opzelura brand for next year. Right now from the feedback that we're receiving, we're confident that we will have a competitive overall coverage also for next year. And that will include, obviously, the pediatric indication if we had to -- to fruition.
Operator: Next question is coming from Kelly Shi from Jefferies.
Kelly Shi: Just curious for the Phase 3 trial ruxolitinib cream in the mild to moderate HS. What is the rationale for using most stringent and the primary endpoint on HiSCR75 over typically use the HiSCR50?
Steven Stein: Kelly, it's Steven. Thanks for the question. So firstly, there's a lot of unmet need in mild to moderate HS defined in our study as people with abscess and nodules of account of about 3 to 10, no draining tunnels. And those patients can have a reasonable placebo effect because of the disease phenotype I just described to you. So that's -- looking at HiSCR75 will help to control for that. It's a higher end point, a higher bar, obviously, address the unmet need and hopefully eliminate a large placebo effect to get it across the finish line. It's agreed with regulatory agencies, and we're a go on the program.
Operator: Our next question today is coming from Matt Phipps from William Blair.
Matt Phipps: I had another question on 262. The clinical trial recently showed the addition of 25 mg arm to that CSU trial. Can you give us any rationale for that? I assume that is maybe not going to be included in the Q1 update? And also just thinking about the profile here. Are you guys -- should we think most about I guess, competing with the recent BTK data as far as another oral? Or do you look at maybe some of the more effective treatments like the kit inhibitors as far as efficacy goes?
Pablo Cagnoni: Yes, Matt, thank you for the question. So the reason for the 25 is to have -- to explore the full range of doses. So as you point out, there's an ongoing study 50 versus 150 versus placebo. That's the data that we're going to have in the first quarter of 2025. We decided in the meantime to start a second study with 25 milligrams versus placebo in order to have the full range of doses explored. So if we have positive data in the ongoing study, then we'll be ready with the 25 already running to be -- to get to a Phase 3 study faster. So that's the idea of the 25-milligram, to explore the full range of dose of 262 in patients with CSU. In terms of worry fits, I mentioned a few times before that we don't necessarily expect to send the same level of efficacy that you may have with the kit antibody. When you deplete all mast cells, which is what kit antibodies do, obviously, the efficacy is very strong. In our opinion, that comes with a series of side effects that have been well reported. I think with BTK inhibitor is a little bit cleaner in terms of safety profile. We think 262, if it shows positive data in CSU, will fit perfectly after antihistamines. Once patients progress in antihistamines, what we expect to be a very clean safety profile for a very convenient daily pill will be ideal for those patients before they need to try more aggressive alternatives. So that we continue to believe is a perfect fit for 262 in CSU.
Operator: Your next question today is coming from James Shin from Deutsche Bank.
James Shin: For ruxolitinib creams HS Phase 3, what time point is the HiSCR75 being assessed? When I look at the pipeline slide, it shows the approval range starting around mid '27 time frame. So is Phase 3 HS data for RUX cream expected in '26?
Steven Stein: Yes, it's Steven. It's hard to be given much precision beyond what we showed in that for the moment because of the study has to start and be underway and then see how it enrolls. The endpoint is HiSCR75 as agreed with regulatory agencies. And we'll update at a more appropriate time and try to give more precision on the endpoint. We expect, given the unmet need, the lack of competition in the space and the excitement around this, that it should enroll well, but we'll see how it goes at a later time.
Operator: Next question today is coming from Vikram Purohit from Morgan Stanley.
Vikram Purohit: So we had one on the oncology pipeline. For the Phase 1 data sets expected for the mutant CALR program and then also for the JAK2V617 programs in 2025. Could you help us understand just the scope of those data releases that we could expect to see and how you'll be gauging success for these initial data sets? And if I could squeeze a question in on the base business. For Opzelura, could you just give us a sense of how utilization is tracking in terms of tubes per patient per year for both AD and vitiligo versus your last update?
Pablo Cagnoni: Let me take the first one on the pipeline. So the mutant CALR antibody program is ahead of 617F. As we disclosed previously, our 617F program this year started in healthy volunteers to understand the formulation better and then we advanced it into in myelofibrosis patients, and it's now in patients, but it's a little bit behind mutant CALR antibody. We expect both to have meaningful data available next year, but that data will be comprised as basically a fairly large number of patients with single agent, particularly for the mutant CALR antibody and some of the data also in combination. I think it's difficult to start putting numbers around what success looks like. What we've been consistent about is that what we expect to see in addition to obviously addressing some of the signs and symptoms of myeloproliferative neoplasms is to see some evidence of decrease in VAF for allele reduction with these medicines. And we expect that we will have that data next year when we decide the right timing to disclose to provide an update.
Steven Stein: On Opzelura utilization, for AD, we still see over 2 tubes per patient per year. For vitiligo, we're missing up the cohort we're following throughout the time to make sure that the cohort is meaningful enough and as well as we follow long enough to a very reliable number. On what you see on the prescription side is that the growth rate is actually coming from new patients as well as refill. So we continue to improve over time. At the same time, we're increasing the focus on the overall adherence, and we have quite exciting programs kicking off this quarter and the first quarter of next year to actually put more emphasis on this part of support for our patient population.
Operator: Your next question today is coming from Derek Archila from Wells Fargo.
Derek Archila: Congrats on the quarter. Just 2 quick ones. Just on 262. I just want to know if you've characterized the tryptase reduction you've seen with the agent in the earlier-stage trials. And then just on the base business, just in terms of what we've seen with Jakafi in the MF market, it looks like you're still driving new patient volumes. Just was wondering if that's more share gains or just the overall market growing?
Pablo Cagnoni: Let me take the first one on 262. So we are measuring tryptase in the ongoing trials. A word of caution, I think that the degree of the magnitude of tryptase reduction that we expect to see is not the same you'll see with depletion of mast cells by using a kit antibody. I mean it's just in the sense that if you deplete mast cells regardless of their location, you're going to have, particularly those in circulation, you're going to have pretty dramatic [indiscernible] tryptase in circulation. What we address with 262 is MRGPRX2 in the mast cells in the skin. As a result of which the decrease in tryptase that we may see, it's not going to be quite as dramatic. But we are measuring that and we will report it.
Steven Stein: Derek, yes, as far as the myelofibrosis market goes, Jakafi, as we said, continues to grow. Total patients increased 4% in myelofibrosis. But in fact, yes, the overall market is growing. Patients are getting first line. They're starting earlier because now, you have multiple agents to go to after Jakafi and patients are being treated in the second line, third line and even fourth-line setting, which we had not seen before.
Operator: Next question today is coming from David Lebowitz from Citibank.
David Lebowitz: Just following up on the Jakafi question. I understand that the step down in the catastrophic out-of-pocket costs are in the middle, they'll be at their lowest $2,000 per year next year. Has that played any role in the uptick in Jakafi growth in the current quarter? And then looking forward to later in the year, could you outline what type of data we might actually see at ASH?
Matteo Trotta: So I'll take the first question and hand it over to Steven or Pablo. So yes, so Jakafi, well, what we always believe that Medicare Part D patients who are cancer patients, out-of-pockets should really not be a barrier to use. So really getting rid of the catastrophic coverage this year for patients on Medicare Part D was a very good thing, going to $2,000 out-of-pocket next year is a very good thing and especially smoothing over the whole period of time. So patients out of pocket in any given month is better. But really, the growth that we see is coming from demand and mostly as we've said, from polycythemia vera and mostly, that's because physicians are starting patients earlier on Jakafi and polycythemia vera because of the results largely from MAGIC PV, which demonstrates that patients will have thrombosis free survival improvements when they start Jakafi and when they start Jakafi earlier. Steve?
Steven Stein: Yes, David, it's Steven. Unfortunately, it's premature to comment on what will be seen at ASH. We have to wait for the acceptances, and then we will provide the update at that point.
Operator: Your next question is coming from Marc Frahm from TD Cowen.
Marc Frahm: Just on 262, back to adding the 25-milligram dose. Can you just talk about kind of what led to adding that? And was it informed at all by the AD trial, which I believe this market has completed as of over the summer. And then just when you get the data from those different dose levels in CSU, you obviously, you don't necessarily need to match the kit antibodies from an efficacy perspective given the potential for improved safety here. But what is that kind of minimum bar that would justify use of a branded drug after antihistamines in your mind?
Unidentified Company Representative: Yes. So let me -- first of all, the decision to start with it’s indeed a new study, it was the ongoing study, but it really is a totally separate cohort with 25 milligrams versus placebo. They had nothing to do with any data that we've seen from the program. We made that decision early in the process very soon after the transaction closed, and it was based on our desire to be ready for a Phase 3 study as soon as possible once we have data. That decision was made at that time. In terms of the bar, look, all the patients in the ongoing study are refractory to antihistamine. So basically, after that, the question is what's the best option for these patients? We believe in that context, obviously, showing efficacy over placebo and with what we believe will be an excellent safety profile will be sufficient for 262 to be the first option after antihistamines in some of the patients with CSU. We remain convinced that, that is the right place for this drug to be used, assuming obviously efficacy in the randomized trial.
Operator: Next question is coming from Brian Abrahams from RBC Capital Markets.
Brian Abrahams: Congrats on the quarter and all the progress. Maybe on the CDK2, I'm curious if there's any updates on the aspects that you're considering as you think about the next steps and pivotal plans into the upcoming FDA meeting and sort of how you're thinking about the balance between exploring late line versus maintenance? And then any more color around the companion diagnostic for that drug?
Steven Stein: Yes, Brian, it's Steven. Thanks for the question. So as Pablo said in his slides, there are numerous areas we're interested in. But broadly speaking, the ovarian cancer settings divided into a platinum refractory and a platinum-sensitive setting divided by a time period of approximately 6 months, although that's getting gray in terms of retreatment. And there are different unmet needs in each population, and we're interested in both. You saw the data update at ESMO. We got upwards of north of a 30% response rate, but the data is still maturing and there may actually be late responses where it may go up. So we really like the profile we've seen. We've done 200 plus patients of dose range in work. So we think we're in a very good place to pick both a dose and schedule. In the platinum refractory ovarian cancer setting, there are potentially 2 ways of thinking about it. For the U.S., primarily the FDA, one could do a single-arm study in that setting, looking at response rate and durability of response to get it across the finish line. As potential confirmatory study and for ex U.S. approvals, that will require a randomized study in that setting. And as it was on the slide deck that would be against investigator choice chemotherapy of which their numbers, their single-agent [indiscernible], et cetera, with a time to event endpoint, like progression-free survival. And we like the profile of the drug there. The other setting that's of extreme interest to us, and we spoke about it at ESMO quite a lot, is the platinum-sensitive ovarian cancer setting, particularly where bevacizumab maintenance is used. And the disease gets a little complicated here because you look at HRD-proficient and HR deficient patients in terms of use of PARP inhibitors. But if you just focus on the majority population there, the HR deficient patients, the majority of those are Cyclin E1 positive. We're doing safety work now with CDK2 and bev maintenance, and that's an enormous interest to us. There's need there. We can potentially improve cure rates, and it would be a pretty simple construct in terms of design, it will be bev maintenance plus placebo versus bev maintenance plus CDK2, and we're doing the enabling work for that now. That is obviously a longer study and we'll deliver later. But we like the profile of the drug there that we've seen so far in terms of its therapeutic ratio. So those are the areas of interest in terms of study designs. On the companion diagnostic, we haven't given details per se on what our cutoff is, but there's 2 ways of looking again at this population. You can look at the gene in terms of amplification, the CCNE1 gene, and others are doing that or you can look at protein of expression by IHC, Cyclin E1 expression, and that's where we focused. And that is a much bigger population. Without cutoff, it's probably more than half of ovarian cancer right now. But we need to have more discussions with regulators and CDH on our companion diagnostic and the cutoff we use in. But the data we showed at ESMO was using our assay with the cutoff that we've determined internally.
Operator: Next question is coming from Andrew Berens from Leerink Partners.
Unidentified Analyst: This is [indiscernible] on for Andy. So with the upcoming HS straight out for povo, just one question, looking ahead to the commercial dynamics. So the efficacy look strong relative to other agents being developed for HS, even now it's oral. I was wondering how you see the safety of povo and if the JAK class concerns are reflected on the label, how might that impact the drug commercially? I guess I'm asking if you anticipate a black box like other JAK agents.
Steven Stein: Yes, it's Steven, I'll address that. I mean we've spoken a bit about how well the studies are going. The Phase 2 profile we saw with the HiSCR100 upwards of 29%. And in fact, enrollment is going very well. It is an inflammatory disease. So there is a reasonable chance or more than a reasonable chance that it will have class effect labeling in terms of a black box. So we do expect that to be the case going forward. If you look at the profile of a JAK-STAT inhibitor versus a biologic, which will only attack, by definition, one pathway, for example, IL-17. Here, we can have more broad coverage of different interleukins, and then potentially that would result in better disease control as we saw in the Phase II data, and that's the data set we'd like to rate.
Operator: Our next question is coming from Andy Chen from Wolfe Research.
Andy Chen: I'm curious if you can remind us the size of your sales force and how it's spread across heme and derm and others? I'm trying to figure out if your SG&A would trend up as you get your topical into pediatric AD into PN and also your JAK inhibitor. Are you going to double down on the derm sales force? Or are you going to capitalize on the existing synergies?
Herve Hoppenot: So I guess in the U.S., Matteo can speak about that. I mean the big picture is that we have established around the world, in fact, now in most of the European countries, in the U.S. and in Canada, we have a dermatology IAI teams that are in place and are sized in a way where we anticipate that they will be able to be -- to do most of the work required for the launches of the new indication, absolutely clearly for Opzelura. When povo comes up, it may be a marginal increase, but nothing that is very, very high. I mean how many people do you have now in the U.S., Matteo?
Matteo Trotta: The full footprint across all teams is around a couple of hundred people. It's -- we see it in line with other competitors. We also saw competitors staffing up a full field force dedicated to HS. We look forward to see the Phase 3 data next year. But from what it looks like now, it's going to be a mix of exactly staffing up throughputly while capturing synergy with the current footprint we have.
Operator: Next question is coming from Jay Olson from Oppenheimer.
Jay Olson: Congrats on the quarter. Since you have a number of catalysts in the near term that could reshape the future top line growth, can you talk about which 1 or 2 catalysts are most important? And are there any gaps in your portfolio? And how are you thinking about business development strategy over the next year?
Herve Hoppenot: Yes. Maybe I'll take that. I mean so if you go to the slide, we just presented in the Slide 10, I mean it's basically saying what has happened recently is the decarbonization of the increase in probability of success for [indiscernible] Niktimvo is approved in third line and retifanlimab in SCAC. And as I said in my presentation, we, collectively, if you put them together, you end up with something that would be around $800 million. So each of them are relatively modest, if you want to classify them. But when you put them together, this is a meaningful contribution to the top line by 2030. What we have coming soon is povo, CDK2, ruxolitinib XR and tafasitamab in first-line DLBCL. So that's, again, the number of projects that have been -- where the probability of success has increased with recent events. I mean, for CDK2, clearly, the data is good. For povorcitinib, the Phase 2 data that we have accumulated is showing very good level of efficacy. And in fact, the follicular lymphoma data for tafa, which is the first of the CD19, CD20 combination is in some way improving our chances of success in the first-line setting, where we are also doing CD19, CD20 combination. So that's the second step. And then we go into mCALR, X2, 617F, [ zilurgisertib ] all the early pipeline that is moving very well. So what it does to us in terms of business development is really looking at maybe early technology type of deals where there are always things we can acquire, learn from that we would be interested in or in the very hypothetical situation where we would find some of that, some very late stage like commercial products that would be also of quality that we would ask for, which is not very common in oncology and dermatology and are very expensive. So in some way, we are in a position today where our internal pipeline plus the acquisitions that we have done or the [ busy ] we have done recently is giving us a portfolio that works very well for what we need to compensate the Jakafi patent exploration around 2029. And we are not looking in the very short term at acquiring new assets that would require a lot of R&D expenses. And that's why we look at either early or very late with contribution to the top line that will come very quickly.
Operator: Next question is coming from Gavin Clark-Gartner from Evercore ISI.
Gavin Clark-Gartner: Also had one on 262 in CSU. I'm just wondering how many patients are [indiscernible] naive versus experienced in the study? And if you think there could be any potential subgroups with greater efficacy, such as IgE low patients?
Unidentified Company Representative: So thank you for the question. So we're not going to provide any details on prior therapy in the study other than to say that all patients have refractory to antihistamines. In terms of the potential for certain subsets to have better efficacy, I'd rather not speculate at this point in time. Obviously, it's a very different mechanism for [indiscernible], which is, as you know, an anti-IgE antibody as opposed to 262, they work in a different pathway, but I'd rather not speculate at this point into the -- about the results, the future results of the study.
Operator: Next question is coming from Evan Seigerman from BMO Capital Markets.
Evan Seigerman: I'm just thinking about the ALK program readout in 4Q. I know you don't want to speculate too much, but maybe comment on kind of your confidence in the readout. It feels like this program has a few ups and downs despite the mechanistic rationale. Can you maybe highlight what gives you this confidence in the update and really in the program overall going forward?
Steven Stein: Yes, Evan, it's Steven. As we've been alluding to over the last year, we've sort of have to go to higher and higher doses to try and achieve the desired effect of the program, which just to remind you, would work potentially through inhibiting hepcidin and then relieving that break so that iron gets released and patients' hemoglobin improves from the underlying disease and then potentially from drug-induced disease. And I think it's safe to say at this point in time, we haven't seen to date yet sufficient efficacy to trigger a go on a future registration program. We'll update more data at the end of the year at an appropriate meeting and give you more color on that. Just to remind you, though, we do have an ongoing program in that continues to enroll with ALK2.
Operator: Your next question is coming from Tazeen Ahmad from Bank of America.
Tazeen Ahmad: As you think about the HS opportunity, can you clarify for us how you think it would be different for RUX cream versus povo? And also, do you have a sense, I know it's still a little bit early, but in terms of usage of tubes for RUX cream in HS, how do you think that will compare relative to what you have seen so far for AD and vitiligo?
Steven Stein: So it's Steven. On your first question. So there's a spectrum of disease that goes mild, moderate and severe in HS. They're called Hurley stages, classifications by the number of abscesses and nodules, the number of draining tunnels and fistulas. Just to address the mild to moderate for which the cream is targeting, as I said earlier, the abscess nodule count there is limited to less than 10. To get on to our particular study, you have to have 3 to 10 abscess nodule count. There are no draining tunnels of fistulas in the mild to moderate population and the HiSCR75 will be the endpoint. And they're approximately up to between 100,000 and 150,000 patients with this, with a lot of unmet need. These patients tend to be underdiagnosed in the setting and tend to have disease for a long time before getting appropriately diagnosed and seeking treatment, and it may need chronic treatment. It's hard to determine now until we conduct the study and get the readout to exactly how long that would be. In terms of povorcitinib, it's looking at the right spectrum of the disease. So the moderate severe population with higher abscess nodule counts with the presence of fistulas and draining tunnels. And then the endpoints can go towards potentially, as Pablo said in his prepared remarks, complete resolution of everything, abscess and nodules and removal of the draining tunnels and fistulas, which will be called a HiSCR100, obviously addresses a huge unmet need and takes care of a lot of morbidity. And again, chronicity of treatment and how many tubes will be needed will come from the Phase 3 study readout, but it will tend to be long therapy, if you want to just ballpark it at the moment.
Operator: Next question is coming from Srikripa Devarakonda from Truist Securities.
Srikripa Devarakonda: And congrats back on the quarter. I had a question about the CDK2 program. I know some of the questions were already answered. But one of your peers just announced the discontinuation of their CDK2 program. I was wondering if you can help us understand how you see the competitive landscape given your data. And before you have the conversation with the FDA or before you move into pivotal trials, should we expect to see any additional data from either ovarian cancer or any of the other indications that you're investigating the drug in?
Unidentified Company Representative: Let me take that question. So in terms of competitive landscape, the competitive landscape for CDK2, it's a little bit beyond the mechanism, right? I mean we think when it comes to ovarian cancer, we are ahead in terms of developing a CDK2 program. We are -- we disclosed the data, as you know. We have over 200 patients treated. We explore a range of doses. We've seen clear evidence of efficacy and a very, very manageable safety profile. So we intend to start registrational studies next year, which I think that puts us in front when it comes to CDK2 inhibition in ovarian cancer and perhaps also in endometrial cancer. We're doing additional work in other indications. Now the company landscape is a little bit more complicated than just CDK2 because there's a number of ADCs being developed in ovarian cancer. Obviously, bevacizumab is approved for certain patients with full receptor alpha expression. There are other ADCs, the same target as well as additional targets for ADCs. I think that the 2 points I would make is, number one, there isn't complete overlap when it comes to populations, at least now with receptor alpha-positive patients. Perhaps for some of the others, the overlap will be it'll be more pronounced. But one of the reasons why we believe the maintenance study in combination with bevacizumab is very important for us in the long run because that might be the perfect setting for an oral, convenient, well-tolerated molecules such as our CDK2 inhibitor. So while we intend to move aggressively into platinum-resistant patients to get a faster market strategy there, we believe the maintenance will differentiate our CDK2 program, not only from other entrants in the same target but also against ADCs.
Operator: Our final question today is coming from Ren Benjamin from JMP Securities.
Ren Benjamin: Congrats on the quarter. I guess just when we think about the potential for positive Phase 3 data from STOP-HS1 and HS2, do you need even like longer-term follow-up data? Or do you feel that you can file kind of right away? And assuming an approval in 2026, how do you see this being used in relation to currently approved therapies? And what kind of market share do you think you might ultimately achieve? I know Steven has talked about greater than 300,000 patients, but how many patients do you think you might be able to treat?
Steven Stein: So Ren, it's Steven. I'll at least do the first part to your question. And obviously, we can't speak about a lot of the regulatory aspects, but it is an NDA, a first filing. So there'll be safety data that will be needed, and we'll provide updates at the appropriate time, but we continue to guide to a 2026 approval for that at the time. In terms of -- it will be really up to what you see ultimately in terms of the efficacy profile vis-a-vis other orals or biologics in terms of use. There are a lot of patients with the disease, a lot of unmet need, and there'll be a lot of cycling through therapy. I think the numbers we give is between 150,000 to 300,000 patients with this moderate to severe in total, in terms of seeking therapy potentially and then use of biologics versus orals, et cetera, will depend on the profiles of the drugs from the Phase 3 setting.
Operator: Thank you. We reach end of our question-and-answer session. I'd like to turn the floor back over to Ben for any further closing comments.
Ben Strain: Thank you all for participating in the call today and your questions. The IR team will be available for the rest of the day for follow-up. Thank you, and goodbye.
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.
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