Note: This is an earnings call transcript. Content may contain errors.

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DATE

Tuesday, Oct. 28, 2025, at 8 a.m. ET

CALL PARTICIPANTS

  • Chief Executive Officer — William Meury
  • President, Head of R&D — Pablo J. Cagnoni
  • Chief Financial Officer — Tom
  • Chief Commercial Officer, U.S. — Mohamed Issa
  • Chief Medical Officer — Steven Stein

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TAKEAWAYS

  • Total Revenue -- $1.37 billion, representing 20% year-over-year growth in Q3 2025.
  • Net Product Sales -- $1.15 billion, up 19% in Q3 2025, driven by broad portfolio performance.
  • Jakafi U.S. Sales -- $791 million, a 7% year-over-year increase in Q3 2025 with 10% year-over-year demand growth and maintained market share leadership in myelofibrosis (MF).
  • Raised Jakafi Guidance -- New full-year expectation for Jakafi is $3.05 billion to $3.075 billion.
  • Opzelura Sales -- $188 million globally, a 35% increase in Q3 2025; U.S. net sales were $144 million, a 21% increase, supported by strong prescription demand and improved formulary status.
  • International Opzelura/Vitiligo Sales -- $44 million, representing a 117% year-over-year increase in Q3 2025 with France, Spain, Italy, and Canada accounting for over 80% of sales and growth.
  • Naktinvo Sales -- $46 million, up 27% sequentially in Q3 2025; 90% of U.S. bone marrow transplant centers have adopted the drug, and 80% of early patients remain on therapy.
  • Monjuvi and Zynyz Launch Contributions -- These new launches supported the revised guidance upward for the year.
  • 2025 Full-Year Net Product Revenue Guidance -- Increased to $4.23 billion to $4.32 billion.
  • 2025 OpEx Guidance -- Maintained at $3.25 billion to $3.31 billion (combined R&D and SG&A expenses) for full-year 2025.
  • GAAP R&D Expense -- $507 million in the third quarter, up 7% year over year, reflecting increased late-stage investment in Q3 2025.
  • GAAP SG&A Expense -- $329 million in the third quarter, up 6% year over year, primarily due to international product launch support.
  • Operating Leverage -- Ongoing operating expenses rose 8%, while revenues increased 18% in Q3 2025, supporting margin expansion
  • Povorcitinib Phase 3 Data in HS -- 24-week results showed 62%-70% of patients reported mild or no pain, with durable improvements across multiple skin and symptomatic endpoints for povorcitinib in hidradenitis suppurativa.
  • Regulatory Timeline for Povorcitinib -- EU submission by year-end; U.S. filing in early 2026 with potential launches in late 2026 or early 2027.
  • Solid Tumor Pipeline Advancements -- TGF-beta by PD-1 bispecific (INCA 33890) showed a 15% response rate in MSS colorectal cancer and is progressing to phase 3 in 2026.
  • KRAS G12D Program (INCB 161734) -- Produced a 34% objective response rate in advanced pancreatic adenocarcinoma, with an 86% disease control rate at 1200 mg in a phase 1 trial of INCB 161734 (KRAS G12D inhibitor), and transitions to further study.
  • Hematology/Oncology Pipeline Streamlining -- Multiple preclinical and early-stage programs were discontinued to prioritize higher-potential assets.
  • mCALR Antibody Program (989) -- Pivotal trial in essential thrombocythemia (ET) targeted for first half of 2026; myelofibrosis pivotal trial likely in second half of 2026.
  • Enfuse Device Partnership -- Enables home-based subcutaneous administration for 989, targeting MF pivotal trial readiness in 2026.
  • Jakafi XR Launch -- Anticipated mid-2026, with a projected 15%-30% conversion from immediate release by 2028 and a slower erosion curve.
  • Opzelura EU Regulatory Filing -- Application for atopic dermatitis to be submitted by year-end, with launch targeted next year.
  • Cost Structure Strategy -- Management underscored a focus on strategic prioritization, with protected funding for growth drivers and ongoing cost controls in non-core areas.
  • Business Development Priority -- Chief Strategy Officer tasked with strengthening business development capabilities to align with long-term growth.

SUMMARY

Incyte (INCY +0.59%) management emphasized a refined commercial and R&D strategy anchored in prioritizing high-value assets and streamlining the pipeline, leading to the discontinuation of several early-stage programs. Intensive launch preparations are underway for three major products -- Ruxolitinib XR, Opzelura AD in Europe, and povorcitinib in HS -- with each targeting differentiated indications and offering potential incremental revenue streams beginning in 2026. The meeting outlined key late-stage oncology and hematology pipeline commitments, including phase 3 initiations for TGF-beta by PD-1 bispecific in colorectal cancer and pivotal trial advancement of the mCALR antibody, both positioned to address high-need populations and extend the growth horizon beyond Jakafi’s loss of exclusivity.

  • CEO Meury said, offers the same therapeutic benefits of Jakafi and a more convenient once-daily dosing regimen, with regulatory submission planned before year-end 2025 and launch anticipated mid-2026.
  • Pablo J. Cagnoni stated, both our TGF-beta by PD-1 and our KRAS G12D programs represent significant opportunities to address large patient populations with high medical need, specifically MSS colorectal cancer and pancreatic ductal adenocarcinoma.
  • Povorcitinib phase 3 results in hidradenitis suppurativa highlighted sustained efficacy and rapid pain improvement, with 62% to 70% of patients reporting mild or no pain by week 24, reinforcing pipeline differentiation and supporting filings in two major territories.
  • International Opzelura momentum continued, with management targeting a two- to threefold increase in the non-U.S. topical business over the next several years following upcoming EU launches.
  • Pivotal registration trials for the mCALR antibody (989) in ET and MF are planned for 2026, with an emphasis on clinical and molecular endpoints as potential disease-modifying standards for myeloproliferative neoplasms.
  • Operational leverage improved as revenue growth outpaced expense increases. W. Meury reiterated every R&D dollar and every SG&A dollar has to serve a business strategy.

INDUSTRY GLOSSARY

  • MF: Myelofibrosis, a type of bone marrow cancer.
  • ET: Essential thrombocythemia, a chronic blood disorder.
  • GVHD: Graft-versus-host disease, a complication following bone marrow transplant.
  • HS: Hidradenitis suppurativa, a chronic inflammatory skin condition.
  • SVR25/SVR35: Spleen Volume Reduction of 25%/35%; clinical trial endpoints indicating tumor burden response in MF.
  • TSS50: Total Symptom Score 50% reduction; a patient-reported outcome metric in MF.
  • VAF: Variant Allele Frequency, a molecular marker measuring mutation load.
  • MSS: Microsatellite stable, describing a genetic subtype of colorectal cancer.
  • PFS: Progression-free survival, a clinical trial endpoint.
  • CD34-positive: Marker for hematopoietic stem/progenitor cells used in disease monitoring.
  • BMT: Bone marrow transplant.
  • Bet Inhibitor: Inhibitors targeting bromodomain and extra-terminal proteins, explored in cancer treatments.
  • PTRS: Probability of Technical and Regulatory Success.

Full Conference Call Transcript

William Meury: Thank you, Alexis, and good morning, everyone. On our last call, I told you I'd be taking a fresh look at the company with a focus on getting the core business right, our R&D priorities right, and our cost base right. This, of course, is a continuous process and one that is well underway and on track. In terms of the core business, my assessment has reinforced my confidence in the growth potential of our key products. As we announced today, we had a strong quarter with total revenues of $1.37 billion and product sales of $1.15 billion. This represents a 20% and 19% increase, respectively, versus prior year.

The fundamentals around Jakafi, Opzelura, and our hematology business, Naktinvo and Monjuvi, namely, remain strong. Our job right now is to keep it that way and to identify effective ways to optimize the promotional strategies and investment for these products to drive future growth. Jakafi Q3 sales reached $791 million, a 7% increase, with strong demand growth of 10% year over year. Growth was broad-based across all three indications. In MF, Jakafi utilization continues to increase, and we are maintaining market share leadership despite competition. Growth in GVHD remains strong, supported by our portfolio strategy with Naktinvo, which is helping identify patients across multiple lines of therapy.

PV is our largest growth driver, fueled by compelling MAGIC PV data showing impressive thrombosis-free survival. Based on this momentum, we're raising our full-year guidance for Jakafi to a new range of $3.05 billion to $3.075 billion. Opzelura growth was exceptional in the third quarter and continues to be a significant contributor to revenue, with $188 million in sales, a 35% increase versus prior year. Of this, $144 million in net sales came from the U.S., which represented a 21% increase versus prior year. The increase was based on strong prescription demand across both indications and more favorable formulary placement at the three top PBMs.

In July, we reorganized the Opzelura sales force into two dedicated sales teams, one for AD and one for vitiligo, to ensure execution and sustained growth. The market for branded non-steroidal topicals continues to expand at a 20% rate as more patients migrate off and away from topical corticosteroids. Given the efficacy of Opzelura in terms of rapid itch relief and skin clearance, our broad prescriber base and formulary coverage, we're well positioned to take advantage of this market dynamic. Internationally, sales for Opzelura and vitiligo total $44 million, representing a 117% increase from last year.

France, Spain, Italy, and Canada account for over 80% of our sales and growth, and we plan to file an application for ruxolitinib cream in moderate AD in the EU by year-end, with a potential approval in the second half of 2026. Now, in its third quarter post-launch, Niktimvo continues to outperform expectations across all launch metrics. Sales in the third quarter totaled $46 million, an increase of 27% versus the second quarter. 90% of US bone marrow transplant centers have adopted Niktimvo, with all centers placing repeat orders year to date. Importantly, 80% of patients who started treatment in the first quarter of launch are still on therapy today.

We have captured 13% of the third line plus GVHD opportunity in just the first nine months on the market. In line with expectations, Niktimvo is primarily being used in the fourth line, with increasing preference and utilization in the third line. Feedback from US bone marrow transplant centers has been positive, with real-world efficacy and safety being equally as impressive as the clinical data. Finally, we're actively studying Niktimvo in combination with ruxolitinib and steroids in earlier line settings. Our combination study with Jakafi is designed to enable a steroid-free regimen in GVHD, which could shift the standard of care. Our combination study with steroids in the front-line setting has the potential to deliver benchmark efficacy and steroid tapering.

This franchise strategy has the potential to significantly increase our addressable market and strengthen our leadership position in GVHD. Our broader hematology and oncology portfolio also performed well this quarter. Sales for Monjuvi in follicular lymphoma, and Zynyz in SCAC, both launched this year, saw strong growth and contributed to our raised guidance. These products will be incremental contributors to our portfolio and collectively can deliver meaningful sales growth over the next several years. We have three important new product launches next year: Ruxolitinib XR, Opzelura AD in Europe, and povorcitinib in HS. I've completed a thorough review of the launch plans and believe these products have the potential to contribute significantly to Incyte's future growth.

Strategically, Ruxolitinib XR, upon approval, offers the same therapeutic benefits of Jakafi and a more convenient once-daily dosing regimen. The stability data are on track to be submitted to the FDA before end of year, with an anticipated launch in mid-2026. As it relates to Opzelura AD, as mentioned, we plan to submit our application in the EU with an anticipated launch next year. Assuming approval, Opzelura has the potential to contribute meaningfully to future sales in the EU and Canada and to overall growth, given its clinical and economic value proposition. With the moderate AD indication in Europe, we could potentially increase our international topical business by 2 to 3x over the next several years.

Finally, povorcitinib could be the first oral option for patients with HS, which is perhaps the most challenging disease in dermatology. It's a multicytokine disease involving many pathways, making treatment more complex and results more variable. A treatment option like povorcitinib, which has shown rapid pain relief and skin clearance scores of over 50%, will be very marketable. We believe there's a substantial opportunity in HS, which is the first step for POVO. Our ongoing developments in PN and vitiligo will come into focus next year, and if positive, further strengthen the position of POVO in our derm portfolio. Together with Opzelura, we could provide a topical-to-oral offering for patients across HS, vitiligo, and PN.

Launch activities for each product remain on schedule, including preparations for the sales force, payer engagements, and medical education initiatives. We'll share more details in early 2026. Turning to R&D, our ongoing pipeline review is providing us with absolute clarity about which high-value programs are core to future growth and have the greatest potential to create value and outsize returns. We want to configure a balanced pipeline that is not consumed by either safe, low-value projects or moonshots. We've set clear go/no-go criteria for moving key projects forward. We will invest and take calculated risks in key programs rather than thinly spreading investments across many programs. In other words, fewer, smarter investments versus diffuse spending.

We'll fund what matters and, importantly, watch out for false positives and negatives. As it relates to our developing pipeline, the first calling capital is hematology. This is the central identity of the company and an area where we have differentiated knowledge and capabilities and an asymmetrical advantage. This includes targeted therapies for MPNs, including mCALR-617, our mCALR bispecific, and discovery programs. We have a window of opportunity here to trigger an innovation-based shift in MPNs from non-specific symptomatic therapies like Jakafi and HU to targeted mutation-specific therapies like 989. Next steps for 989 and 617 will be shared later this year and next year.

In terms of our solid tumor program, the cornerstone of our cancer strategy is novel biological pathways, high-incidence cancers with substantial medical need that missed the IO revolution, and immunotherapies and targeted therapies that can be used frontline in combination with standard-of-care regimens. As you know, we have three programs in early development: KRAS G12D for pancreatic cancer, TGF-beta by PD-1 bispecific for MSS colorectal cancer, and CDK2 for ovarian cancer. Over the next several months, we will collect more data on these programs in terms of response rates, duration of response, and safety, particularly in combination with standard of care.

We'll move forward without delay, provided our data continue to be objectively competitive, and we can be early to market and defend our position long term. Now, in terms of our operating expenses and overall cost structure, we're conducting a review of the entire business, which focuses on prioritization and data-driven trade-off decisions. Our objective is to manage costs but not underfund critical initiatives and compromise growth prospects. We'll strike the right balance between financial discipline and long-term strategic investments, which can be achieved by controlling costs in low-value areas to free up capital either for reinvestment in high-value opportunities or to improve margins. Our framework for the 2026 budget and beyond will be based on the following.

First, define and ring-fence our strategic growth drivers. This means the new product launches that I touched on, as well as key R&D projects, which we have earmarked as non-negotiable, fully funded programs. Once we protect the growth drivers, we're looking to control costs in areas that add less or minimal strategic value. From there, the savings we've identified and achieved will either be reallocated or banked. This will be a continuous process, not a one-and-done exercise. It's a mindset. As our business evolves, so will our resource allocation. Finally, business development.

BD works when you have strong strategic leadership, high throughput, and a framework for rapidly triaging opportunities and making decisions, which requires a skilled search and evaluation team and a deep network. To be successful, we need to operate inside the loop in our focus areas. Accordingly, Dave Gardner joined Incyte as Chief Strategy Officer in September, and one of his priorities is to build out this capability. He will play a central role in developing our long-term growth strategy and ensuring external business development opportunities and internal portfolio decisions are strategically sound and financially compelling. We will share more details about our strategic review early next year. Now, I'd like to turn the call over to Pablo.

Pablo J. Cagnoni: Thank you, Bill, and good morning, everyone. As shown in slide 14, our pipeline is strategically focused, with numerous high-impact programs currently in development. Over the past few months, we have conducted a thorough pipeline review to ensure we're concentrating our efforts and resources on the projects that are essential to the future growth of the company. As Bill mentioned, this process was guided by a clear set of go/no-go criteria, enabling us to make strategic decisions about which programs to advance. As a result, we have decided to pause or stop several preclinical and early clinical stage programs, including INCA 34460, our anti-CD122 program, INCB 57643, our BET inhibitor program, and the development of povorcitinib in chronic spontaneous urticaria.

By continuing to streamline our pipeline, we will be able to accelerate and prioritize the programs with the greatest potential impact to patients and to drive future growth. Now, I'd like to focus on key updates from the quarter, highlighting recent advancements with povorcitinib and our solid tumor franchise. I will also discuss what's expected for the remainder of 2025 from our mutant CALR antibody program. For povorcitinib, last month, we presented longer-term data in hidradenitis suppurativa at the European Academy of Dermatology and Venereology Congress, which further reinforced the differentiated profile of povorcitinib.

The 24-week data demonstrated deep and sustained improvements across key clinical endpoints, including HiSCR 50, 75, 90, and 100, resolution of draining tunnels, and effective reduction in flares. Povorcitinib also showed a rapid and robust reduction in skin pain, with 62% to 70% of patients reporting mild or no pain by week 24. Physicians experienced in the management of HS emphasize that their primary focus when they treat patients with HS is on two elements: help patients feel better by addressing the pain related to HS and to effectively control flares. The data percentage showed that povorcitinib provides rapid and sustained pain relief and reduces the frequency of flares.

These positive phase 3 results demonstrate the potential of povorcitinib to address the significant medical needs of the more than 300,000 people living with moderate to severe HS, offering a novel, effective, and convenient oral treatment option for this underserved patient population. Moving to slide 16 and the near-term opportunities for povorcitinib. As you know, HS is the most advanced program. We're on track with our regulatory submissions by the end of the year in the EU and early 2026 in the U.S., with potential approvals and launches in late 2026, early 2027. In addition to HS, we're studying povorcitinib in three other indications, underscoring its potential to become a major growth driver for the company.

Povorcitinib has been evaluated in phase 3 programs in vitiligo and prurigo nodularis, as well as a phase 2 proof of concept study in asthma. We anticipate pivotal data readouts for vitiligo and PN in 2026, with a goal of potential initial regulatory approvals in 2027-2028. Next, I would like to highlight two recent updates from our solid tumor portfolio, beginning with our TGF-beta by PD-1 bispecific antibody program. This month, at the European Society of Medical Oncology annual meeting, we presented initial phase 1 data for INCA 33890, also referred to moving forward as 890. Our first-in-class TGF-beta receptor 2 by PD-1 bispecific antibody in patients with solid tumors.

This is an Incyte discovery compound and one that is truly differentiated from other TGF-beta and PD-1 approaches. The phase 1 trial evaluated 890 in solid tumors with a focus on microsatellite stable or MSS colorectal cancer patients. 890 demonstrated durable single-agent anti-tumor activity and a manageable safety profile in heavily pretreated MSS colorectal cancer patients, a population with limited treatment options and where anti-PD-1, PD-L1 antibodies have historically produced response rates from 0 to 2%. In patients with MSS colorectal, 890 achieved an overall response rate of 15%, and most notably, responses were observed in patients with and without liver metastases. The majority of treatment-related adverse events were low-grade, with no dose-limiting toxicities reported.

We have also completed a dose escalation of 890 in combinations of four cohorts: FOLFOX plus bevacizumab, FOLFIRI plus bevacizumab, bevacizumab, and cetuximab. No evidence of additive toxicity has been observed in any of the combination cohorts, and dose expansion is ongoing. This initial result provides a strong rationale for advancing 890 into a registrational program. We're planning to start a pivotal phase 3 trial evaluating 890 in combination with standard-of-care chemotherapy and bevacizumab in first-line MSS colorectal cancer patients in 2026.

Turning to our KRAS G12D program on slide 18, we recently presented encouraging clinical data from the phase one trial of INCB 161734, or as I'll refer to moving forward, 734, in heavily pretreated patients with advanced or metastatic solid tumors harboring the KRAS G12D mutation, including pancreatic ductal adenocarcinoma, among others. Results demonstrated a manageable safety profile with no dose-limiting toxicities observed and predominantly grade 1 treatment-related adverse events. Importantly, in pancreatic adenocarcinoma patients, 734 showed promising anti-tumor activity with an objective response rate of 34%, disease control rate of 86% at the dose of 1200 milligrams. These results are particularly notable given that only eight of the patients were treated in the second-line setting.

To summarize, both our TGF-beta by PD-1 and our KRAS G12D programs represent significant opportunities to address large patient populations with high medical need, specifically MSS colorectal cancer and pancreatic ductal adenocarcinoma. As Bill noted, our strategy in both cancers will be to win in front line in combination with standard of care. For 890, we have demonstrated durable single-agent activity in heavily pretreated MSS colorectal cancer patients, including those with liver metastases, and a favorable safety profile and combinability with first-line standard of care regimens. As previously mentioned, we're planning to initiate a phase 3 study in first-line MSS colorectal in 2026.

Similarly, 734 has shown promising anti-tumor activity and manageable safety profile in advanced solid tumors, with particularly encouraging results in PDACC. We'll share more updates on this program next year. Now to slide 20. 2025 has been a pivotal year for Incyte, highlighted by multiple new product launches, pivotal trial readouts, phase 3 study initiations, and proof of concept results. These accomplishments reflect the solid progress we've made so far toward the milestones we established at the beginning of the year. As we look at the remainder of the year, we plan to share data for the first time on 989, our mutant CALR antibody in patients with myelofibrosis.

We are evaluating 989 in a broad population of patients with MF. There are three actively enrolling cohorts. First, intermediate to high-risk patients who are intolerant, ineligible, or resistant to a JAK inhibitor. This cohort is evaluating 989 as a monotherapy. Second, intermediate to high-risk patients who are on ruxolitinib but experience a suboptimal screen response after at least 12 weeks of treatment. In this cohort, we are evaluating adding 989 to ruxolitinib. Finally, we're enrolling patients with intermediate to high-risk treatment-naive MF in a cohort evaluating 989 compared to a combination of 989 and ruxolitinib. This will allow us to see how 989 performs as a monotherapy and in combination with ruxolitinib in treatment-naive patients.

Our update later this year will include early data from the first two cohorts. For the monotherapy cohort, we plan to share data from roughly 50 patients. Approximately two-thirds of them will have more than 24 weeks of follow-up. Additionally, data will be presented for the combination cohort and at least 15 suboptimal responders to ruxolitinib. More than half of these patients will have a minimum of 24 weeks of follow-up. Importantly, the update will include response data using traditional endpoints: SVR25, SVR35, TSS50, and anemia, and molecular endpoints like effects on VAF in whole blood, CD34-positive mutant CALR cells in peripheral blood mononuclear cells, and mutant CALR-positive omega-kerasites in the bone marrow.

Additionally, we'll provide an update on 989 treated patients with essential thrombocythemia as a follow-up to the encouraging results presented earlier this year. As you'll recall from EHA presentation, 989 demonstrated the rapid and sustained normalization of platelet counts and was well tolerated, with only one patient discontinuing due to an adverse event. We look forward to sharing updates on the remaining 2025 milestones and to provide further visibility into our 2026 catalyst as we continue to advance our pipeline. With that, I'll turn it over to Tom for a financial update on the quarter.

Tom: Thanks, Pablo. As Bill mentioned earlier, our total revenues and product revenues were $1.37 billion and $1.15 billion, respectively, increasing 20% and 19% from the prior year. Our total GAAP R&D expenses were $507 million in the third quarter. Excluding one-time expenses in the prior year, R&D expenses increased 7% year over year, driven by continued investment in our late-stage development assets. Moving to SG&A, total GAAP SG&A expenses were $329 million in the third quarter, increasing 6% year over year, primarily driven by international marketing activities to support product launches.

Ongoing operating expenses in the third quarter increased 8% year over year, compared to an 18% increase in ongoing revenues during the same period, leading to a continued increase in operating leverage and margins. Based on the growth of our product portfolio, we raised 2025 full-year net product revenue guidance to $4.23 to $4.32 billion. We maintain our prior OpEx guidance of $3.25 to $3.31 billion, which reflects combined R&D and SG&A GAAP expenses. I'll now turn the call over to Bill.

William Meury: Thanks, Tom. That concludes our prepared remarks. Please open the line for Q&A.

Operator: Certainly. We'll now be conducting a question-and-answer session. If you'd like to be placed into the question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. As a reminder, we ask you to please ask one question, one follow-up, then return to the queue. Our first question today is coming from Tazeen Ahmad from Bank of America. Your line is now live.

Tazeen Ahmad: Hi guys, good morning. Thanks for taking my question. I wanted to focus on the upcoming mCALR data. You've given us a good preview of how many patients' worth of data to expect. I think most people are going to be focused on the monotherapy arm. How important is that going to be for people to believe that you have convinced efficacy as a standalone? There could potentially be the view that, you know, it could be synergistic when added to Jakafi. Can you maybe level set for us what level of efficacy you're going to think is going to be convincing enough to move it forward, even if it's in combination with Jakafi? Thanks.

William Meury: Thanks, Tazeen. I'll turn it over to Pablo.

Pablo J. Cagnoni: Thank you for the question. I think it's important to remember a couple of things about our mutant CALR antibody program. The first is this is the very first targeted therapy for patients with MPNs. We're talking about MF, but broadly speaking, for myeloproliferative neoplasms, both MF and ET in this case, this is the first truly targeted therapy, as opposed to non-specific therapies in the past, including ruxolitinib, that were mostly symptomatic improvements with very little effect on disease modification. You're asking specifically about the update at ASH. I think it's very important for us to demonstrate that there is single-agent activity with 989.

That's why the update will include a large number of patients, as I mentioned, 50 patients with somewhat significant follow-up to really prove convincingly that 989 has single-agent activity. The focus will be not just on clinical endpoints, which we believe are critical: spleen reduction, symptom improvement, anemia, but also a set of translational endpoints, which we think are really important to confirm our view that this new medication has potential disease-modifying effects. In terms of benchmarks around efficacy in previously treated patients with JAK inhibitors, I think the best benchmark we have recently is momelotinib. As you know, momelotinib has an SVR35 of between 7% and 22% in different studies, with the TSS50 improvements in the 25% to 26%.

Those are some reasonable benchmarks in the second-line setting to look at. It's very important for us to confirm the single-agent activity of 989 in MF patients, Tazeen.

William Meury: Tazeen, thanks for the question.

Operator: Thank you. Next question today is coming from Andrew Behrens from Lyrinx Partners. Your line is now live.

Andrew Behrens: Hi, thanks, and congratulations on the execution during the quarter. I was wondering if you could give some more color on the decision to terminate the povorcitinib program at CSU following your announcement in April that this phase 2 is successful. Are we going to see the data at a medical meeting as you previously guided?

William Meury: Yeah, Andy, I'll start off and then turn it over to Pablo. As it relates to povorcitinib for CSU, it came down for us to priorities. We have to, when we are prioritizing projects with better returns profile, it was a good phase 2 program, but we have better phase 3 programs. The factors that went into the decision included differentiation, competitive intensity, timing to market, and market potential, among other factors. Pablo, you want to just comment on the release of the data?

Pablo J. Cagnoni: Certainly. We haven't decided with investigators whether to release the data, but we'll almost certainly do that at some future conference, Andy. The one other point I would add to Bill's points is that in addition to those factors, the regulatory bar in CSU, we discussed with FDA, and the requirements for potential pivotal program in CSU were pretty onerous, and we decided we had other priorities to focus on. Okay, thanks. If I could, just a question on the PD-1, TGF-beta. I was at ESMO. I thought it was really encouraging, and you guys are advancing into phase 3. Are we going to see combination data before you make that decision to advance?

Is there, like, I think there's a run-in, it looks like, on the clinical trial side?

Pablo J. Cagnoni: The decision to advance the TGF-beta by PD-1 program in combination with chemotherapy first-line colorectal is made. We're moving forward in that direction. In parallel with that, we're generating data with a combination, and we will release that data at some point next year, Andy. Those two things are happening in parallel. We think speed is of the essence here in executing this phase 3 trial. We're advancing this rapidly, and we'll generate the data and release it at some point.

Operator: Thank you. Next question today is coming from Stephen Willey from Stifel. Your line is now live.

Stephen Willey: Yeah, hi, good morning. Just two quick ones from me. On 989, I was just wondering if you could give a little bit of color around what we should expect to see within the abstract publication next week, just relative to the presentation itself. A quick one on Naktinvo. Curious how you're thinking about Sanofi's failed frontline trial with Resurrect steroids in terms of read-through to the ongoing phase 3 trial with Naktinvo and just whether you think that might say anything about the biology of the disease being different in a newly diagnosed patient. Thanks.

William Meury: Yeah, thanks. Thanks for the question, Steve. I'm going to turn the second question about Naktinvo over to Steven Stein, and then Pablo will grab the first question.

Steven Stein: Yeah, Steve, thanks for the question. In terms of first-line graft-versus-host disease in combination with steroids, there's really a little bit of controversy around how you measure the primary endpoint and event-free survival. There's some nuances there on what you call events. We think our definition is robust and is powered to adequately show the difference we need to beat steroids. As Bill said in his prepared remarks, to also show something doctors very much desire: steroid withdrawal as rapidly as possible to avert side effects. You're right in the sense that it shows the difficulty in this arena of beating steroids, which are active.

We really think it's around the definition of the endpoint, and our endpoint is robust and meets the needs for our program, and we're confident about it. Thanks.

William Meury: Thanks, Steven. The only other thing I would add, Steve, here is we fortunately with Naktinvo have two shots on goal. We have the combination study with steroids and with Jakafi. Obviously, these are calculated risks. You get a combination study with Jakafi that's positive, and you're going to 2X the addressable population, and then you have a steroid-free regimen. Obviously, we want both these programs to work. If one of two work, it could change the trajectory of Naktinvo fairly significantly. Pablo, you want to address the first question?

Pablo J. Cagnoni: Certainly. With 989, I think it's important to focus on the presentation we'll have before the end of the year. That's a later data cut. It's going to have more patients, and it's going to have longer follow-up. I realize that the abstracts will be released, but I would ask you to wait for the update we'll provide before the end of the year and focus on that because it's more substantial, and particularly follow-up is substantially longer.

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

Jay Olson: Oh, hey guys, congrats on the quarter, and thanks for taking the questions. Can you describe the rationale behind terminating the BET inhibitor program? Was that mostly related to your strategic focus on targeted therapies like mCALR and myelofibrosis? As a follow-up to that question, since the BET inhibitor was on track to begin registrational studies, how soon can you move mCALR into registrational studies? Thank you.

William Meury: Jay, thanks for the questions. I'll take the first part and then turn it over to Pablo. As it relates to the BET inhibitor, the risk-benefit calculus, as you know, for BET inhibitors right now is complex. Differentiating class-wide risks from molecule-specific ones is challenging. In general, we're prioritizing programs with a higher PTRS and a clearer path to market. That was fundamentally why we stopped the BET inhibitor program. I'll let Pablo comment further.

Pablo J. Cagnoni: I don't have anything to add in terms of the reasons for terminating that program. In terms of the CALR antibody program, Jay, the goal is to start one or more pivotal trials in 2026. As we mentioned during our EHA update in ET, ET will likely be the first pivotal trial we start, and that should start at some point in the first half of the year. In parallel with that, we are having regulatory interactions and continue to review the data in order to decide the right trials and the timing for implementing phase 3 trials for patients with myelofibrosis that most likely start at some point in the second half of 2026.

I think that one thing that I would like to emphasize is the termination of the BET program in no way reduces our ambition in MPNs. As I mentioned earlier this year, our goal by the end of the decade is to have a solution for every single patient with a myeloproliferative neoplasm. We're building a pipeline of targeted therapies to address that need, and we intend to continue to advance those programs.

William Meury: Thanks, Jay.

Operator: Thank you. Next question today is coming from James Shin from Deutsche Bank. Your line is now live.

James Shin: Good morning. Thank you for the question. The first one is for Pablo. Pablo, I appreciate 989 as a targeted therapy for MPNs, but can you say whether or not we should expect SVR, TSS, and anemia burden, at least on the kinetics front, to look similar to RUX? A follow-up for Bill, Jakafi's COMFORT-I and II set a high bar for frontline myelofibrosis. From a timing, financial, and regulatory perspective, can you share insights and progress on gaining certainty for 989's frontline MF development path? Will that development path align with Jakafi's LOE? Thank you.

William Meury: Thank you. All right, Pablo, you can take the first part of the question.

Pablo J. Cagnoni: Thank you for the question. It is very important for us to address your question directly. It's very important for us to demonstrate that 989 has an effect on clinical endpoints in myelofibrosis. That's why the presentation will include SVR25, SVR35, TSS50 effect, and effects in anemia. We realize those are a combination of those are the approval endpoints in MF, and showing efficacy in those same points is critical for this program. Those will be part of the update we provide before the end of the year. Let me pass it back to Bill.

William Meury: Yeah, and as it relates to both 989 in ET and MF and how we think about the business post-2029, filling a revenue gap is not what 989 does. What 989 does is build a long-duration revenue and cash flow stream well into the next decade. We do not see the end of the road. Here is how I think about second line, first line. Pablo commented on this. There are targeted treatments available in many other cancers. That is not true in MPNs. For hematologists, there is intrinsic appeal to the first targeted therapy. When you take a look at ET, hydroxyurea is a standard of care.

It is the most widely used cytoreductive agent in ET, but it achieves only a partial response, not a complete response in most patients. There are three consequences to that. The first one is residual symptoms, not as significant as it is in MF, but residual symptoms. The second consequence is residual thrombotic risk. The third consequence is residual transformational risk. 989 solves the problems that HU created. Even in a second-line single-agent study or with those data, I expect that 989 will reshape the use of hydroxyurea where patients transition off of therapy rapidly because 989 is targeting disease-causing cells. It is better tolerated. For example, HU has seven warnings and precautions, and it is easier to dose.

The market for ET is about $5 billion. ET mCALR patients, roughly half of them are resistant or intolerant to therapy. I think there is a clear glide path to growth in ET with the first study. As it relates to MF, it is, of course, a completely different type of MPN. The risk of transformation to leukemia is real. It is more aggressive. It is more symptomatic. As effective as Jakafi is, as you know, the SVR35 is between 30% and 40%. Symptoms are in the mid-50%. Everybody on Jakafi progresses. Even in a second-line setting, there is going to be, just like in ET, a move to either add 989.

We will have to, of course, produce that data or use 989 after Jakafi. I think that the opportunity in both MF and ET is fairly significant. What we are looking to is build a business well into the next decade. If we start the studies in the middle of 2026, give or take, we should be getting out sometime in that 2029-2030 period. Thanks for the question.

Operator: Thank you. Next question today is coming from Salveen Jaswal Richter from Goldman Sachs. Your line is now live.

Salveen Jaswal Richter: Good morning. Thanks for taking my questions. You've highlighted VAF as an important part of the mCALR story in terms of the MPN story in terms of the drug being a functional cure. Just remind us what you want to see on VAF reduction and level set us on how well understood the ultimate correlation is between VAF and clinical outcomes. A second question here, Bill, you've highlighted your focus on managing operating expenses and streamlining the company. How are you thinking about the evolution of the company's target margin profile over the next few years and also through the Jakafi LOE? Thank you.

William Meury: Great. I'll turn the first question, Salveen, about molecular response over to Pablo, and then I'll address your question about OpEx after that.

Pablo J. Cagnoni: Thank you for the question, Salveen. We have three, and it's important to remember, we have three molecular endpoints that we're going to report data on before the end of the year. One is VAF in whole blood. The other one is CD34-positive mutant CALR cells in peripheral blood mononuclear cells. The third is malignant megakaryocytes or mutant CALR megakaryocytes in the bone marrow. The reason why I'm emphasizing those three is because VAF is, in a way, a lagging indicator of what's happening in the bone marrow, which is what truly matters.

The disease originates in the bone marrow, and reducing malignant megakaryocytes in the bone marrow, which is something we showed for ET at EHA this year, is the critical disease-modifying effect. That then will translate into reduction of CD34-positive mutant CALR-positive cells in peripheral blood, and that in turn, over time, will be reflected in a reduction in VAF. I think I would emphasize that it's important to look at all three components of the translational endpoints, and we'll talk about all three before the end of the year.

In terms of correlations, we know that VAF is a bad thing, and we've shown some data in ET that patients with lower VAF, with slightly higher VAF reductions over time, have better hematologic responses in ET. That data are important. We still believe that more likely than not, initial approvals for 989 will be based fundamentally on clinical endpoints, traditional clinical endpoints, a combination of the endpoints that we know, which are spleen, symptoms, and anemia. That's the way we're building these pivotal trials for next year. I'll pass it back to Bill.

William Meury: Yeah, thanks, Pablo. As it relates to OpEx, Salveen, it's a good question. I spent a lot of time thinking about it. As you implied in your question, we have to take a multi-year view of the budget. I'm not necessarily hard coding for OpEx as a % or R&D as a % of sales, but I do expect that the quantum of at least spending growth or the % is going to come down. I expect it to come down because of an increase in sales and leverage. Here's what I will say: every R&D dollar and every SG&A dollar has to serve a business strategy.

Budgeting is about distinguishing the high-value projects, as you know, from the low-value projects. Another way to put it is good costs from bad costs. What we're really solving for, though, is creating the steepest growth curve possible post-2029 and a long-duration revenue and cash flow stream. We will streamline costs where possible, but not underfund critical initiatives and compromise growth. Those are the principles as I think about OpEx, and I do expect our margins to improve over time, in part due to increasing sales and good cost control. Thanks for the question.

Operator: Thank you. Next question today is coming from Peter Lawson from Barclays. Your line is now live.

Peter Lawson: Great. Thanks for taking the questions. Naktinvo, kind of how sustainable is the trajectory on that growth? It's really impressive this quarter, and I wonder if you could also talk around the profitability of that franchise.

William Meury: Peter, could you just repeat the question? It was a little hard to hear.

Peter Lawson: Oh, yeah, sorry. On Naktinvo, if you could talk through the sustainability of the trajectory. It was really impressive this quarter, and if you could talk through the profitability as well.

William Meury: Yeah, I'll start off, and if Mohamed, who runs that business, has any additional comments, he can contribute too. You're right. It's off to a very, very good start. You know, we're annualizing almost at $200 million a year. I think the important point about the launch right now is you do have virtually every BMT center in the United States using and purchasing Naktinvo, which I think is very, very encouraging. All the feedback we've got from transplanters is very, very positive. As you know, we're in the third, fourth quarter of a launch, and launches early on can be unpredictable from quarter to quarter.

All I can tell you is I think the growth trajectory of this is solid right now. If you look at the Resurrect curve, when it launched, we're virtually right on top of it. That product, you know, they had a tough quarter, but it's roughly a $500 million business. I think the prospects for growth next year are solid. We'll, of course, share guidance in early 2026, but I don't see any red flags right now other than launches can be a little bit unpredictable and uncertain. I like the way it looks. The next comment I would make as it relates to profitability, you know, one of the nice things about this product is it's a specialty product.

We're not covering 10,000, 20,000, 30,000 physicians, or several thousand hospitals. We have a very targeted audience of BMT centers across the United States. When you look at the margin profile of a product like this, it's very healthy. That's what I can tell you about profitability. I wish more of them were as profitable as Naktinvo. Mohamed, do you have anything else you want to add?

Mohamed Issa: Yeah, thanks, Bill. Maybe just to complement and give you some color on the sustainability of the growth. You know, as Bill mentioned, a really broad penetration with 90% of transplant centers picking up Naktinvo, but we're seeing all of them have repeat orders year to date, which speaks not only to the trial utilization but the repeat utilization within these accounts, and the feedback continues to be positive. Another point on the sustainability of the trajectory is, in line with our expectations, most of the utilization today is happening in the fourth line, but we're seeing a lot more preference and increasing preference in the third-line setting, which gives us a lot of headroom left to go.

Maybe one last point on the sustainability. You know, our goal that we communicated on the last call was to have about 1,000 active patients on therapy by the end of the year. Through the first nine months, we have about 800 or so patients well on our way to that 1,000-patient goal by the end of the year, and that continues to be promising as well.

From a contribution margin, maybe just the last note is, you know, this contribution margin for the Naktinvo P&L is one of the higher in our portfolios, and we expect it to continue to be such given the level of focus that we have on the product and the level of focus from a commercial execution.

William Meury: Great. Thanks, Mohamed. Thanks for the question, Peter.

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

Evan Seiderman: Hi guys, thanks for taking the question. Great to see a lot of you at ESMO. I think we'd all agree that mCALR is a very critical juncture for Incyte, but I want to take it out of the picture for a second. Can you walk me through how the current pipeline needs to mature to drive growth through the Jakafi LOE? What type of business development, you're not going to be specific, would you have to do to help also supplement that growth? Essentially, I want to understand what Incyte looks like with and without mCALR by the end of the decade. Thank you so much.

William Meury: Thanks for the question, Evan. Yes, and it was nice to see you at ESMO too. Here's how I would look at the pipeline. We're focused on seven drivers, seven projects that I think have the potential to create very meaningful value. Not all of them have to work. Not all of them will work. We're not going to be perfect. We have povorcitinib, which is a three-indication product. We can build a JAK-anchored franchise in dermatology, where we have differentiated knowledge and capabilities and a very solid data set. The second project is 989, and I can't take it out of the picture, Evan. That's an important project.

We have 617F, which is still early stage, a little bit more opaque, but as we de-risk that asset, that could be as big or bigger than 989 in MPNs because it's covering a mutation that's much more frequent. In fact, it could be 2X the size of a 989. We have three solid tumor programs, which we de-risked at ESMO. We still have more data to collect. We have KRAS G12D for pancreatic cancer, TGF-beta by PD-1 for CRC, and CDK2 for ovarian cancer. What I would say here is that we're systematically and deliberately, and at least up until ESMO, quietly building a high-impact oncology portfolio. There is a lot of substrate there.

I don't expect all these necessarily to work. If one or two of those hit, they could be very, very meaningful. As we talked about at the start of the call, novel compounds against novel biological targets in cancers that have missed the IO revolution, where there's significant medical need, and we're positioning all three compounds frontline in combination with standard-of-care chemo. The seventh project that I focus on is Naktinvo. As Mohamed talked about, we're off to a good start. There was a question about sustainability. We have two combination trials in place. If one of those combination trials hit, we're one for two. We move this into the second line.

If it's the combination trial with Jakafi, we have a non-steroid regimen, and you could 2X the value of that business. When you think about the flow across all of our three verticals, I&I, hematology, and oncology, there's some real substrate there. We don't need to be perfect. We just need two or three of these out of the seven to hit, and we'll build a business that's bigger than the one that we have post-2029. Thanks for the question.

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

Derek Archila: Hey, good morning, and thanks for taking the questions. I'm just curious for 989's pivotal trials in MF and ET expected next year. Will these be with IV or with the on-body pump from Enfuse? In terms of a potential XR launch and kind of a commentary around the launch plans in the prepared remarks, I guess how do you plan to position with payers? I guess what's your base case in terms of the amount of shares you can convert from Jakafi pre-generics? Thanks.

William Meury: Yeah, good question. I'll make a few comments about ENABLE and XR and then ask Pablo and Mohamed. First, we're really pleased to strike a partnership with ENABLE. They specialize in high-volume subcutaneous administration with products with a range of 5 mL to 25 mL. We also like the device because it's at-home, self-administered, comfort, the efficiency of their manufacturing operation. I think it's a high-quality company. They're expanding their manufacturing site, which is an FDA-approved manufacturing site. They have commercial devices, I think, in roughly 25 countries and about 8,000 units. This is a high-quality company. Pablo can talk more about the program. As it relates to XR, Pablo, why don't you speak, and then we'll go to XR?

Pablo J. Cagnoni: In terms of the plan to incorporating Enfuse into the pivotal trials in MPNs, ET is pretty far along. We showed an update at EHA a few months ago on the data. The data has continued to mature. We have already initiated regulatory interactions around that. We're probably going to be ready to start pivotal trial in ET before we're ready to deploy the Enfuse device. For MF, the goal is to, as quickly as possible, make the Enfuse device available and ready to go so we can start those studies with the subcutaneous administration. However, I can be firm at this point.

We need a little bit more time to really figure out the timing for the implementation of this, but that would be our goal for MF.

William Meury: Good. Mohamed, you want to talk about XR?

Mohamed Issa: Yeah, if I can put that in frame for us real quick, Derek. Jakafi XR, as you know, represents a great addition to the portfolio, expected to launch in the middle part of 2026. HCPs and patients now are going to have a convenient once-daily formulation of a brand that they know and trust. We expect about 15% to 30% conversion from the IR by 2028. With a slower erosion curve than IR, XR can be a solid incremental contributor to top-line sales through 2030 and beyond. Our launch strategy is focused on securing quick formulary access, accelerating HCP adoption, and patient preference to maximize that uptake in the short term for that long-term value.

If I can just point to our ability to launch Naktinvo, FL in Monjuvi, and Zynyz in SCAC, I'm just proud of our team's ability to execute on these launches, and I think XR won't be any different.

William Meury: Great. Thanks, Mohamed. Thanks for the question.

Operator: Thank you. Next question today is coming from Ash Verma from UBS. Your line is now live.

Ash Verma: Hi, thanks for taking our questions as well. A lot of focus on 989. Maybe just looking at this slide 20, a few different settings that you're exploring in ET and MF, but just wanted to confirm at this point, are you able to pursue first-line or naive patients in registration studies? Secondly, on the formulation, where are you able to get the volume down to, like how many mL? Is this something that can be a home subcutaneous injection and not just an on-body formulation? Thanks.

William Meury: Thanks, Ash. Pablo, you want to take that?

Pablo J. Cagnoni: Certainly. Thank you for the question. I think the first part was about first-line MF. The answer is we fully intend to develop 989 for first-line patients with myelofibrosis. That's why we're running the combination with ruxolitinib in treatment-naive patients. That work is ongoing. We're not going to disclose results on that before the end of this year, but I'm confident that we will find a path there. We have very clear preclinical data showing synergy between 989 and ruxolitinib in the right models of MF. I'm confident that we will find a path there. In terms of the subcutaneous, our goal is to have a device that patients can use at home for self-administration of 989 subcutaneously.

That's the goal. That's why we put in place a collaboration with ENABLE, and we think we're going to find a path for that in 2026.

William Meury: Thanks, Pablo. Next question.

Operator: Thank you. Next question today is coming from Ren Benjamin from Citizens. Your line is now live.

Ren Benjamin: Hey, good morning, guys. Thanks for taking the questions and congratulations on a great quarter. I guess just to follow up with Ruxolitinib XR, there was a strategy way back when about combining it with a pipeline product to help kind of fight this LOE. Are you looking at any potential combinations to move this forward with either the pipeline or in-licensing a product and saving off this erosion curve for Ruxolitinib? As a follow-up, you know you're starting this registrational program with TGF-beta.

I'm kind of curious as you think about how large the study is, the delta that you need to show to have a positive study, how do you come to the calculus given the kind of limited data that you have so far?

William Meury: Ren, thanks for the question. I'll take the first one, turn the second one over to Pablo. Right now, our focus for XR is launching it for the Jakafi indications. We're not working on any combinations in development, and we don't plan to right now. I know that there was a history there, but we're just focused on the once-a-day and preserving some portion of that revenue stream and getting a more convenient dosing regimen out. As it relates to your second question, I'll turn it over to actually Steven Stein.

Steven Stein: Yeah, hi, Ren. Thanks for the question. It's first-line microsatellite stable colorectal cancer. The combination we'll be advancing there, as we alluded to at ESMO, is with FOLFOX and BEV. That's used across the board, independent of RAS mutant versus wild type, independent of left or right-sided tumor. The enabling safety work has already progressed well and will continue. There are benchmarks available both for progression-free survival as well as overall survival. The primary endpoint, as we alluded to at ASH, will be PFS because OS takes a little longer to get there.

The size we'll put up when we launch the study, but you can estimate it's probably north of 500, and we'll be well-powered to show the PFS advantage we want. Thanks.

William Meury: Thanks, Ren. Thanks, Steven.

Operator: Thank you. Next question today is coming from Jessica Fye from J.P. Morgan. Your line is now live.

Jessica Fye: Hey guys, good morning. Thanks for taking my questions. I had a couple more on 989. For Pablo, recognizing that we won't have frontline data for 989 by year-end, can you talk about what elements of these data in post-Jakafi patients and Jakafi suboptimal responders could make us come away confident that 989 could be successful in the frontline? Specifically for that combo data set, I know it's smaller, but what are you going to be looking for as proof points that 989 is offering clear clinical benefit on top of Jakafi in the absence of a control arm?

Is there a certain magnitude of change from baseline on those key measures that you think would exclude any natural variability in the endpoints over time had the patients just remained on their Jakafi monotherapy? I have a follow-up.

Pablo J. Cagnoni: Thanks, Jess. I think that the element, like with any early development program, early-stage development program, looking at the totality of the emerging evidence is important. The first part here is obviously looking at the safety profile. We showed that in ET earlier this year. We'll show it in MF before the end of this year. Because of the exclusively targeted nature of 989, we think that the safety profile, the really excellent profile that we've shown so far, is a key element for the future development. The second part is obviously efficacy. The two components, as I mentioned earlier, are obviously the classic clinical endpoints.

We need to see as monotherapy in patients that are resistant, intolerant, or ineligible for Jakafi. We need to see clear evidence of impact on clinical endpoints: spleen reduction, improvement in symptoms, anemia improvements, in addition to translational endpoints. Now, when you look at the add-on cohort that we're going to show some data, I think it's important to remember that those are the hardest patients to treat. Those are patients that did not respond to Jakafi in an ideal way, despite a minimum of 12 weeks of treatment and being eight weeks on a stable dose. Any improvement on classic endpoints in those patients we think is highly meaningful.

When you look at what's available in second-line MF, the benchmarks are pretty low, as I mentioned earlier, between 9% and 20% for SVR35, for example. In our view, when you combine the monotherapy data in second line together with the ability to combine 989 with Jakafi together with a safety profile, I think it's very easy to put a story together that increases our confidence in our ability to move 989 to the frontline setting as quickly as possible. At some point in 2026, we'll provide an update on the treatment-naive patients, as I mentioned earlier, and that will be the definitive element of that story.

William Meury: Thanks, Jess.

Jessica Fye: Yeah, I had a follow-up. You mentioned looking at SVR25 in addition to SVR35. How do you incorporate SVR25 data into your decision-making?

Pablo J. Cagnoni: We really don't, to be honest with you. We report both 25 and 35, as it has been done in other trials in the past. Some of these patients have relatively short follow-up. We have patients enrolled at a range of doses. As you know, these are dose escalation trials. We think it's important to have directional data where the spleen shrinkage is going. The key element here is SVR35. Make no mistake about that. We report 25 as well, but SVR35 is what we really care about.

Operator: Thank you. Our final question today is coming from Srikripa Devarakonda from True Securities. Your line is now live.

Srikripa Devarakonda: Hey guys, thank you so much for taking my question. Another one on 989. When it comes to a Rux combo, is there a rationale to develop both in suboptimal responders as well as in Rux-naive patients, or do you see it as a better strategy to focus on one versus the other for the longer term? Secondly, what's the FDA guidance for the endpoints? I know you said you need to show both SVR35 and TSS50, but would they be co-primary endpoints? Do you have to hit on both? Thank you.

Pablo J. Cagnoni: Let me take the second part of the question first. We'll have discussions with FDA on the appropriate regulatory endpoints for what is a novel treatment paradigm for patients with MF, which we think 989 represents. We think it's going to be based on clinical endpoints predominantly. What those specific clinical endpoints will be, we'll discuss it with FDA. We think there's an argument to be made about modifying some of what has been done previously in terms of co-primaries for SVR35 and TSS50. The impact on anemia, for example, we think could be very important and very interesting for FDA to contemplate.

In terms of what pivotal trials we will do in MF, those decisions are in the process of being made, and we'll update you over time, probably in early 2026. We intend to develop 989 to try to address the needs of all patients with MF that are mutant CALR positive. That includes patients that are naive or patients that were treated with Jakafi initially and did not respond or were intolerant. In those two contexts, monotherapy and a combination with ruxolitinib potentially can have a role. We'll give you more details over time as we disclose the data.

William Meury: Great. Thanks, Pablo. Thanks, Tom.

Operator: Thank you. We reached the end of our question and answer session, and that does conclude today's teleconference and webcast. You may disconnect your lines at this time and have a wonderful day. We thank you for your participation today.