Incyte Q3 2026 Earnings Call: Revenue Up 14%, Sales Guidance Raised

Key Takeaways

• Incyte reported Q3 2026 total revenue of $1.56 billion, up 14% year over year, while total net sales rose 14% to $1.32 billion.
• Jakafi franchise net sales increased 4% to $827 million, supported by 12% underlying demand growth. Jakafi XR generated $15 million.
• Opzelura net sales grew 36% to $255 million. On a pro forma basis excluding the prior-year Medicaid line-extension settlement benefit, sales increased 21%.
• Core business net sales excluding Jakafi reached $490 million, up 30%, driven by Opzelura, Niktimvo, Zynyz and Monjuvi.
• Management raised 2026 guidance for Opzelura, Hematology and Oncology, and total net sales. The new total net sales outlook is $5.2 billion to $5.3 billion.
• GAAP expenses rose 146% to $2.27 billion, primarily because of a $1.23 billion acquired in-process R&D charge associated with the Vega Therapeutics acquisition.

Core Financial Data

Business and Operating Performance

Jakafi remained Incyte’s largest product. Growth occurred across all indications and was led by polycythemia vera. Reported sales growth trailed demand growth because of expected pricing dynamics, including the CMS model’s impact.

Jakafi XR’s franchise share increased by approximately 100 basis points in September to about 3%. Management expects formulary coverage to exceed 80% by year-end and continues to target roughly $50 million in full-year XR sales. The company’s longer-term objective is to retain 10% to 30% of the Jakafi business by 2029.

Opzelura’s U.S. net sales were $208 million, up 45% year over year. On a pro forma basis, U.S. growth was 25%, supported by 24% demand growth. Management attributed the performance to sales-force expansion, increased promotion to nurse practitioners and physician assistants, and improved formulary access.

In Europe, the European Commission approved Opzelura for adults with moderate atopic dermatitis during July. This added a second EU indication and made Opzelura the first steroid-free topical JAK inhibitor available in Europe for this population, according to the company.

Incyte also continued to expand its late-stage pipeline. Management said six assets are in Phase III development, spanning myeloproliferative neoplasms, von Willebrand disease, pancreatic and colorectal cancers, ovarian cancer, and hidradenitis suppurativa.

For oncology, Phase I data for the 734 KRAS G12D inhibitor showed objective response rates of 58% with gemcitabine plus nab-paclitaxel and 81% with modified FOLFIRINOX in first-line pancreatic ductal adenocarcinoma. In heavily pretreated colorectal cancer, 734 plus cetuximab produced a 36% objective response rate.

The 890 TGF-beta receptor 2 by PD-1 bispecific antibody, combined with FOLFOX and bevacizumab, produced a 71% objective response rate in first-line microsatellite-stable colorectal cancer. The rate was 83% among patients with liver metastases. These remain early clinical findings, and the ongoing Phase III NEXERA-303 study is expected to report top-line data in 2029.

Management Guidance

Management maintained full-year operating expense guidance and expects combined R&D and SG&A spending to fall around the middle of its existing range. Planned spending includes late-stage clinical development and pre-commercialization activities.

The company expects potential European approval of povorcitinib for moderate-to-severe hidradenitis suppurativa by year-end 2026 and anticipates a U.S. decision in the first quarter of 2027. Management also expects the FDA review of Monjuvi in first-line diffuse large B-cell lymphoma to conclude in the first quarter of 2027.

Risks and Areas to Watch

• Jakafi transition: Incyte is building its non-Jakafi business ahead of the 2029 transition, but Jakafi still accounted for most quarterly product sales.
• Pipeline execution: Management said risk has increasingly shifted toward Phase III execution, enrollment and regulatory milestones, although clinical and biological risks remain.
• Regulatory endpoint alignment: The company is discussing alternative and composite endpoints for 989 in myelofibrosis with the FDA. The final first-line study design has not been determined.
• CDK2 program narrowing: Incyte stopped additional site activation and future enrollment in the Phase III MAESTRA-2 study in platinum-resistant ovarian cancer. Development of 667 is now focused on first-line maintenance in cyclin E1-overexpressing ovarian cancer.
• Pricing and access: Jakafi sales were affected by expected pricing dynamics. For Opzelura, management described 2026 as an investment year for formulary access and expects pricing strategy to shift toward maintaining coverage from 2027.

Analyst Q&A Highlights

989 frontline myelofibrosis data: Incyte plans to present data on approximately 55 frontline patients at ASH, including both monotherapy and ruxolitinib combinations. Management cautioned that the presentation’s data cutoff will be roughly four months later than the abstract cutoff. A possible registrational design could include three arms: ruxolitinib, ruxolitinib plus 989, and 989 monotherapy.

Next-generation mutant CALR antibody: Management said the preclinical candidate is 70 times more potent against known type mutations than 989 and has a longer half-life. The company expects it could support at least monthly subcutaneous dosing. Clinical development is targeted for early 2027, with pivotal studies targeted for 2028, subject to regulatory discussions and early trial results.

734 Phase III enrollment: Management said enrollment in the pancreatic cancer study is on track or slightly ahead of internal projections. The company will monitor post-progression treatment use and may adjust country enrollment if necessary.

Povorcitinib label scenarios: Incyte is preparing for either a broad hidradenitis suppurativa label covering pre- and post-biologic patients or a post-biologic label. Management said both outcomes are commercially workable but has not yet seen the final FDA label.

Potential Opzelura expansion into hidradenitis suppurativa: If the mild-to-moderate HS Phase III studies are positive, management estimated the indication could add $50 million to $100 million in sales. This opportunity is not currently included in the company’s models.

Full Earnings Call Transcript

Complete Earnings Call Transcript

Management Remarks

Operator

Greetings, and welcome to the Incyte Third Quarter 2026 Earnings Call. [Operator Instructions] As a reminder, this conference is being recorded. [Operator Instructions]

It's now my pleasure to turn the call over to Alexis Smith, Vice President and Head of Investor Relations. Please go ahead, Alexis.

Alexis Smith

Thank you. Good morning, and welcome to Incyte's Third Quarter 2026 Earnings Conference Call. Before we begin, I encourage everyone to go to the Investors section of our website to find the press release, related financial tables and slides that follow today's discussion.

On today's call, I'm joined by Bill, Pablo and Suketu, who will deliver our prepared remarks. Steven, Dave and Mohamed will also be available for Q&A. I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail.

I'll now hand the call over to Bill.

William Meury

Thanks, Alexis, and good morning, everyone. As we look at the first 9 months of the year, we've made meaningful progress against the strategy we laid out for Insight. That strategy has 2 fundamental components: scaling the core business beyond Jakafi and advancing our late-stage pipeline to drive the next phase of growth. The core business is the foundation. It gives us a scale to navigate the '29 transition and fund R&D. Layering the pipeline on top of that gives us the opportunity to build a significantly larger company over the next decade.

We now have several compounds in Phase III development, including a mutant CALR antibody for MPNs, a Protein S modulator for von Willebrand disease, a G12D inhibitor for pancreatic cancer, a TGF-beta by PD-1 bispecific antibody in colorectal cancer, a CDK2 inhibitor for ovarian cancer and a JAK inhibitor currently under regulatory review in HS.

We have increasing confidence in the biology behind these programs and believe we've taken meaningful risks out of them as they've advanced. That does not mean the risk is 0, but increasingly, the risk we are managing is execution risk, running high-quality Phase III programs, enrolling them on time and achieving the regulatory milestones in front of us. Those are things we directly control, and that is our focus today.

We are fully funding and resourcing these opportunities, leaving nothing to chance. And if we deliver against them, we believe the value creation potential is substantial and that is how we should ultimately be judged.

Now we'll frame the quarter around 3 themes. First, key business performance. Every product grew year-over-year. Jakafi had another strong quarter with growth across all indications and sales from our core business, excluding Jakafi, increased 37% from prior year.

Second, we achieved important regulatory milestones, including the approval and launch of Opzelura for moderate AD in the EU in the third quarter. In parallel, the NDA reviews for Monjuvi and frontline DLBCL and povorcitinib in moderate to severe HS, are well underway.

Third, we continue to advance our late-stage pipeline, including trial initiations and expansion efforts for key programs like G12D, TGF-beta by PD-1 and 989.

I'll now cover the quarter in more detail and then hand it to Pablo to expand on the progress across our pipeline. Total revenue for the quarter was $1.56 billion, representing growth of 14% year-over-year. Total net sales in the quarter were $1.32 billion, up 14% versus the prior year. Growth was broad-based and led by Opzelura and our Hematology and Oncology franchise while Jakafi remained a significant contributor.

Jakafi franchise net sales in the third quarter were $827 million, up 4% year-over-year. Underlying demand remained strong, increasing 12% with growth across all indications led by PV. Net sales growth reflects expected pricing dynamics during the quarter, including the impact of the CMS generous model. Jakafi XR net sales for the third quarter were $15 million. XR share of the franchise increased by approximately 100 basis points in September to approximately 3%. This was driven by both new and existing patients. Formulary coverage is expected to exceed 80% by year-end. The combination of increasing uptake here and expanding market access keeps us on track to achieve our full year end target of roughly $50 million in XR net sales and supports our goal of retaining 10% to 30% of the Jakafi business by 2029.

Now to our core business ex Jakafi, which is one of the clearest indicators of transitioning the company. Net sales from our core business, excluding Jakafi were $490 million, representing a 30% increase versus prior year, reflecting contributions from key growth brands, namely Opzelura, Niktimvo, Zynyz and Monjuvi. The growth across brands and geographies strengthens the outlook for the company as we see this business growing to $3 billion to $4 billion by 2030.

Opzelura net sales were $255 million in the quarter, an increase of 36% over prior year. Net sales were driven by increased demand across geographies and favorable U.S. pricing dynamics resulting from the agreement with CMS related to the Opzelura line extension. On a pro forma basis, which adjusts the third quarter of '25 for the favorable impact of the Medicaid line extension settlement, total Opzelura net sales increased 21% over the prior year period.

Now I'll break down the U.S. and international performance. U.S. net sales in the third quarter were $208 million, up 45% year-over-year and the week 36 assessment allows additional time to capture the full magnitude and durability of treatment benefit consistent with the targeted treatment approach that we believe has the potential to address underlying disease biology. These are established endpoints, consistent with those used for current approved therapies in MF. Notably, we're also evaluating a composite endpoint as a key secondary endpoint.

The composite endpoint is designed to capture the benefits we have of [indiscernible] on spleen and symptoms, including improvements in hemoglobin, [indiscernible] in peripheral blood. This allows us to further characterize the potential benefit of a disease-modifying therapy on key manifestations of MF.

The study is powered to evaluate efficacy in patients in Type 1 mutations who represent more than 70% of the call mutated MAC population and have experienced the most robust clinical responses to date. We will also continue to generate data in patients with non-type 1 mutations to further characterize the potential of 989 across the broader color mutated population.

Looking ahead, we expect to show the first clinical data for 989 in first-line MF by year-end, both as monotherapy and in combination with ruxolitinib. This data will have defined the role of 989 in [indiscernible] treatment setting and in formal of development plans in 2027. Additionally, we plan to share preclinical data on our next-generation mutant CALR antibody, which we will be progressing into the clinic in early 2027.

Together, these efforts reflect our strategy to build a broader portfolio of mutation-directed therapies with the potential to meaningfully change the treatment paradigm for patients with MPNs. Beyond MPNs, we continue to advance important programs across our hematology pipeline. The FDA's review of [indiscernible] first-line diffuse large B-cell lymphoma, or DLBCL, is ongoing with approval expected in the first quarter of next year.

In chronic graft-versus-host disease, we are evaluating [indiscernible] in earlier lines of therapy. This includes a Phase II study of [indiscernible] in combination with ruxolitinib, with results expected at a medical meeting early next year and a Phase III study evaluating [indiscernible] in combination with steroids with top line results anticipated in 2028.

We also expanded our hematology pipeline this quarter with the acquisition of Vega Therapeutics and its lead therapy latarcibart. This novel proteins modulator has the potential to be a transformative nonfactor replacement treatment for von Willebrand disease. The pivotal Phase III study is underway with top line data expected in early 2029. We also plan to share additional data from the Phase I open-label extension later this year.

Turning to Oncology. We have advanced our solid tumor programs from early clinical development to a growing late-stage pipeline. A year ago, we established clinical proof of concept across several novel mechanisms and tumor types. Today, we have pivotal programs underway for our KRAS G12D inhibitor, TGF-beta receptor 2 by PD-1 bispecific antibody and our CDK2 inhibitor with expansion efforts planned for next year.

As we reviewed at ESMO earlier this week, our strategy is to advance novel mechanisms in high incident cancers where outcomes remain poor with a particular emphasis on building a leading gastrointestinal franchise anchored by 734 and 890.

Starting with 734, our G12D inhibitor, our conviction in this program continues to grow, and we are rapidly expanding its development across tumor types, treatment settings and novel combinations. At ESMO, we presented Phase I data evaluating 734 in combination with standard of care chemotherapy in first-line pancreatic ductal carcinoma, or PDAC and in combination with rituximab in heavily pretreated patients with colorectal cancer.

In PDAC, 734 showed encouraging activity in combination with both standard of care chemotherapies with a safety and tolerability profile consistent with this established regimens. Objective response rates confirmed and pending were 58% for 734 gemcitabine and nab paclitaxel and 81% for 734 plus modified FOLFIRINOX. We also see promising signals of durability with 6-month [indiscernible] PFS of 80% and 90%, respectively. The depth of response early into durability and consistent tolerability across both chemotherapy backbones reinforce our confidence in the ongoing Phase III DAWN-303 study and first-line PDAC and support moving 734 into early stage of disease with a Phase III study in adjuvant PDAC planned to start in 2027.

Coming to colorectal cancer. 734 in combination with cetuximab produced a 36% objective response rate in heavily preceded patients. This is notable because anti-EGFR therapy alone has historically produced response rates below 5% in late line colorectal cancer, which suggests a synergistic combination. This data informed the design of our Phase III DAWN-302 study in previously treated colorectal cancer. We reached alignment with the FDA on the design this quarter and plan to initiate the study in the first half of next year.

Beyond this registrational programs, we recently announced clinical collaborations, enabling evaluation of 734 with novel combinations. This include petosemtamab, an EGFR by LGR5 bispecific antibody in first-line colorectal cancer, navlimetostat, a PRMT5 inhibitor in PDAC and SNV1521 PARP1 inhibitor in solid tumors. This Phase I studies will begin next year.

Going to 890, our TGF-beta receptor 2 by PD-1 bispecific antibody. We believe 890 has the potential to service an immunotherapy backbone. Starting in microsatellite stable colorectal cancer or MSS CRC, a disease that has historically been resistant to immunotherapy. At ESMO, we presented Phase I data evaluating 890 in combination with standard of care chemotherapy in first-line MSS CRC. 890 in combination with FOLFOX and bevacizumab showed encouraging antitumor activity with an objective response rate of 71%. Importantly, responses were observed across patient subgroups, including an objective response rate of 83% in patients with liver metastases, a population historically associated with poor outcomes and reduce responsiveness to immunotherapy.

We also see early signals of durability with a 6-month landmark progression-free survival of 81%. We look forward to sharing more mature progression-free survival data next year. This data supports our ongoing Phase III NEXERA-303 study in first-line metastatic MSS colorectal cancer, which is well underway with top line data expected in 2029. We're also moving 890 into earlier treatment settings, including a proof-of-concept study in patients with circulating tumor DNA positive disease following surgery and adjuvant chemotherapy.

Finally, turning to 667, our CDK2 inhibitor. Based on the evolving treatment landscape, we are focusing our development on first-line maintenance in cyclin E1 overexpressing ovarian cancer where we believe the opportunity for 667 is greatest to offer among meaningful treatment option for patients and physicians. As a result, we are deprioritizing development efforts in platinum-resistant ovarian cancer.

The open-label Phase II MAESTRA-1 trial remains ongoing. However, we have made the decision to stop additional site activation and discontinue future enrollment in the randomized Phase III MAESTRA-2 study. This was not an easy decision, and we're grateful to the investigators and patients who participated in this study.

Stepping back, in a short period, we have moved from established proof of concept to advancing multiple registrational programs in Oncology. We have done so by following the data, and we will continue to deliberate about where we invest. With that approach, we believe we're well positioned to build multiple oncology franchises over time.

Turning to IAI, where we continue to build on our leadership in dermatology across topical and systemic therapies. In July, the European Commission approved Opzelura for adults with moderate atopic dermatitis or AD. This approval makes Opzelura, the first steroid-free topical JAK inhibitor available in Europe for this population and expands its EU label into a second indication. Povorcitinib, our oral JAK inhibitor received a positive CHMP opinion for the treatment of moderate to severe HS in adults who have had an inadequate response to anti-TNF therapy. We anticipate a potential approval in Europe by year-end. In the U.S., the NDA is under review with an anticipated approval in the first quarter of 2027.

We also expect several important Phase III readouts by year-end, including top line results from ruxolitinib cream in mild-to-moderate HS and povorcitinib in [indiscernible]. Together, this program's position povorcitinib for potential approval in multiple indications, including HS, PN and vitiligo, building on the foundation Opzelura has established in dermatology.

To close, the pipeline we have today looks very different from a year ago. We have moved multiple novel programs into registrational development, and we have done so deliberately guided at each step by the data. With a more mature and diversified late-stage pipeline, supported by the discovery and clinical engine behind it, we are well positioned to deliver meaningful innovation for patients and support sustainable top line growth heading into the 2030s.

With that, I will turn it over to Suketu for a financial update on the quarter.

Suketu Upadhyay

Thank you, Pablo, and good morning. I'll begin with comments on our third quarter results and then turn to our updated full year outlook. As Bill mentioned earlier, we delivered strong net sales, managed expenses well and executed across all areas of the company. Total revenue for the quarter was $1.56 billion, an increase of 14%. Total net sales were $1.32 billion, reflecting 14% growth versus the prior year, driven by strong product demand. Total GAAP expenses for the quarter were $2.27 billion, an increase of 146% compared to the prior year. This includes a $1.23 billion IP R&D expense related to the closing of the Vega acquisition. Total cash consideration for the transaction was approximately $1.27 billion, including $12.5 billion for the upfront.

When we exclude the Vega related IP R&D expense, total operating expenses for the quarter grew 12%. GAAP cost of goods sold was $109 million, representing approximately 8% of total net sales. This is in line with our expectations, and we expect COGS to be approximately 8% for the full year. Our GAAP R&D expenses were $1.79 billion for the quarter, an increase of 254% versus the prior year, driven by the Vega acquisition and continued investment in our late-stage development assets, across hematology and oncology. Excluding the Vega acquisition, GAAP R&D expenses increased 11% for the quarter.

Moving to SG&A. GAAP SG&A expenses were $364 million for the quarter, increasing 11% year-over-year driven by prelaunch activities for povorcitinib. And lastly, we ended the quarter with $3.9 billion in cash and cash equivalents.

Now turning to our outlook for the remainder of the year. We are maintaining our full year guidance for the Jakafi franchise of $3.22 billion to $3.27 billion. Demand and pricing performed in line with our expectations, and we successfully absorbed the impact of the CMS generous model, which on an annualized basis will be roughly 1% of Jakafi gross sales. We are raising our full year guidance for Opzelura, Hematology and Oncology and total net sales based on the strong performance delivered through the first 9 months of the year.

For Opzelura, we are raising full year 2026 net sales guidance to $1.1 billion to $1.12 billion, reflecting continued growth in both the U.S. and international markets. For Hematology and Oncology, we are raising full year guidance to $890 million to $910 million reflecting the performance across key growth brands. As a result, we are increasing total net sales guidance to $5.2 billion to $5.3 billion.

We're also maintaining our full year operating expense guidance. While unchanged based on our year-to-date R&D investment and expected spend in the fourth quarter, we expect total R&D and SG&A expenses to be towards the middle of a full year range, reflecting investments in our late-stage development pipeline and pre-commercialization efforts. To close, we are pleased with our performance for the quarter and the first 9 months of the year, and we remain confident in our outlook.

With that, I'll turn the call back over to the operator and open it up for Q&A.

Operator

[Operator Instructions] Our first question is coming from Tazeen Ahmad from Bank of America.

Question-and-Answer Session

Tazeen Ahmad

So I just wanted to ask you, what are the key items we should be focusing on for the update for 989 mCALR in the frontline MF study coming up this quarter?

Unknown Executive

Thanks, Tazeen. Pablo will take the question.

Pablo Cagnoni

Tazeen, thank you for the question. So at ASH, we're going to present as promised, an update on the first-line data. Now just as on the side, you remember that at EHA, we presented data in patients that were ineligible for Jakafi. And the data looked quite good in our opinion, both on SVR35 and TSS50 as well the anemia improvement that we've become accustomed to see in patients with 989.

So to complement that or to expand on that at ASH, we're going to have about a total of 55 patients in frontline. Of those, about 20 are in that group of ineligible and the other 40 or so are in true first-line patients that would have been [indiscernible] for Jakafi. There's a split between single agent and combination with ruxolitinib, about 2/3, 1/3 approximately.

And importantly, we have quite a bit of follow-up in those patients at this point. In fact, one of the things that would -- I think it's important to highlight is the data in the abstract are much more immature than the data in the presentation. In fact, the data cut in the presentation about 4 months later than the date in the abstract. So I would ask you when the abstracts come out, which is in the relatively near term, we wait for the data in the presentation because that's a truly relevant data. So I think it's a pretty comprehensive update. I think it will give a clear idea of the role of 989 potential [indiscernible] MF, and we look forward to sharing the data with you.

Operator

Your next question today is coming from Etzer Darout from Barclays.

Unknown Analyst

This is Gustav on for Etzer. My question is on the second line MS pivotal for 989. How will prior JAK inhibitor treatment be defined with the patients into give resistance refractory intolerance and is there a minimum duration of treatment or dose for those?

Unknown Executive

Go ahead, Pablo.

Pablo Cagnoni

I mean the definition is pretty standard in the fact that patients don't achieve ideal SVR35 or the ideal spleen or symptom response to Jakafi or usually, the reason for intolerance is [indiscernible] in most patients. So the physicians make that determination. There's a line within the product but the physicians determination. And there's no minimum duration. I don't believe -- I would have to confirm with the product. I don't believe there's any minimum duration of treatment or dose of Jakafi. The dose of Jakafi prior to entering a second-line study is not predetermined in the second-line study at all.

Operator

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

Unknown Analyst

This is Sylvia on for Jess Fye. Can you elaborate on the strength that you are seeing in Opzelura? And are you able to quantify the gross to net you saw this quarter and how that differed from third quarter '25?

William Meury

Yes, it's a good question. I'll make a few comments and then Pablo, I mean, Mohamed can expand on them. At the start of the year, we made a very deliberate strategic decision to expand the sales force, increase promotion to NPs and PAs and to improve access quality, which required an investment. And if you look at the results this quarter, you focus on 2 key metrics: underlying prescription demand and new patient starts. And it's been strong now for several months. I think it's an important indicator of the strength of the business, not just to finish the year, but in 2027.

Opzelura has a very large prescriber base of 20,000 physicians. We have extensive formulary coverage. And we have probably north of 0.25 million people receiving Opzelura today. And so that is a moat around the business. And our job right now is really simple, keep the pressure on keep our foot on the gas pedal and this business could represent over 1/3 of our core business ex Jakafi when we hit the transition in 2029. And Mohamed and his team has done an excellent job managing this product for the past several quarters.

Mohamed, do you want to add anything?

Mohamed Issa

Yes. Maybe just to quantify a few of the points that you mentioned, Bill. Just to reiterate, in the U.S., we grew net sales 25% on a pro forma basis, which basically accounts for the GTN benefit that you would have seen from the line extension settlement that we declared. And on top of that, right, that 25% was driven by a 24% overall demand growth year-over-year. So the majority of the pro forma growth was driven by demand. And actually, there was a little bit of a price downside on that when you look at it on a pro forma basis.

So the growth of the business is really, really healthy. And a lot of the growth, as you can see, is coming from the brands underlying health of the business, which is demand. And like Bill mentioned, new patient volume, which is really the best measure of competitiveness, grew 2x market when you think about AD and vitiligo. So not only are we growing, but we're growing and we're outpacing the market, which is a really good indicator of not only the health of the business, but our competitiveness overall.

William Meury

Yes. And Sylvia, just to add one thing to what Mohamed just said. When you think about price for Opzelura, 2026 was a year of investment to improve the quality of formulary coverage. When we look out '27 and beyond, think about price as a maintenance strategy. there's a cost to maintaining coverage, but we don't expect significant headwinds as it relates to average selling price for Opzelura.

Operator

Next question today is coming from Salim Syed from Mizuho.

Erik Lavington

This is Erik on for Salim. Congrats on the quarter. One on axatilimab in GVHD. It looks like the first-line [indiscernible] plus RUX readout got pushed out from 4Q '26 to 1Q '27. Just curious about the puts and takes on that and how that is -- how are you thinking about the overall time line on that at this point if that's different?

William Meury

Thanks for the question, Eric. Pablo will take it.

Pablo Cagnoni

So the reason for that is simply 2% the data [indiscernible] been a comprehensive data set at the most relevant meeting, which is in the first quarter of 2027. The data wasn't ready for submission to an earlier meeting. We don't want to just show the primary endpoint we want to show you durability of of the response. We want to show you subsequent therapy, a comprehensive review of the safety profile. So we want to present that at a meeting -- at a scientific meeting and the most appropriate one is in the first quarter of 2027. That's the only reason for shifting the time line a little bit.

Operator

Your next question today is coming from Brian Abrahams from RBC Capital Markets.

Brian Abrahams

Congrats on the continued progress. Maybe one on 989. I guess I'm curious monotherapy or combo activity, do you think you would need to see and KOLs would want to see to warrant development of 989 as a frontline alternative or add-on for treatment-naive call mutated patients, just given the known benefits of Jakafi but also the known AEs?

William Meury

Great. Go ahead, Pablo.

Pablo Cagnoni

So thank you for the question. Let me give you a little bit of a more comprehensive answer here because I think it's important. I know it's in everybody's mind. So we need to -- 2 pieces of data to finalize the design of a frontline study in MF. First of all, let's go back to the comment I made a few minutes ago. We know from the EHA data in ineligible patients that the efficacy 989 untreated, [indiscernible] treated patients with MF is substantial. You all remember [indiscernible] and TSS50 data we showed and the really striking effect on an [indiscernible] improvement. So what we need now is a more comprehensive data set with longer follow-up, which we will have at ASH, including single agent and combination with Jakafi, as you pointed out. We need to see that data in order to decide the final decision on the design of the frontline study.

The other event that needs to happen is we will have a meeting with the FDA with -- a Type C meeting with the surrogate endpoints team to discuss -- continue the conversation that we've had on the use of a composite endpoint to try to shift away from 35 or TSS50, because we believe disease-modifying therapies like 989 need to be looked at differently. We need to address the fact that this medicine basically shifts hematopoiesis back to normal, and that is represented by improvements in anemia, reduction in fibrosis, reduction of mutated [ megacacins ] in the bone marrow, et cetera. that needs to be addressed. So once we complete those conversations with the FDA and once we have the full data set, we will make the decision on the frontline study.

Going directly to your question, we do know that Jakafi produces rapid improvement in symptoms. And SVR35 mutated patients in frontline of approximately 20% to 22%. We think there's a lot of room for improvement there. Whether we need a combination arm in the study or not, we'll decide based on the points that I just made. We do think there might be a role in which case, we'll launch a 3-arm study, which would be RUX versus RUX plus 989 versus 989 alone. That's a perfect legitimate study. Patients and physicians will have 2 options to treat their MF, either single-agent 989 or combination with RUX and all that will be decided in the next few months, and we'll update you early in 2027.

Operator

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

Evan Seigerman

So just taking a step back, the pipeline progress that Incyte has accomplished over the past year has been impressive. Can you just level set kind of remind us what you've accomplished over the past year? And then looking forward, aside from SLR at ASH, what are some things that we should be focused on over the next year so that when we get to the 3Q call, we can discuss those as well?

William Meury

Yes. Thanks for the question, Evan. I agree with you. I think the shape and maturity of the pipeline has changed over the past 12 months. I also believe it is the right balance of risk and reward. In other words, the pipeline is not consumed on one hand by moonshots, and on the other hand, by safe, low-return bets. We sort of have a combination of products that can deliver what I would describe as outsized returns potentially with products that can deliver incremental but reliable growth over time. More specifically, we have 6 assets right now in Phase III. They're not all equal when you think about them on a sort of risk-adjusted value basis.

Povacitinib, 989, 12D and [indiscernible] are comparatively higher PTRS projects. TGF-beta by PD-1, the fifth asset, is different, significant potential value, but more biology risk. So in our strat plan, it has the widest range of possible outcomes, whereas the other 3 or 4 anchor franchises for us. CDK2, the last one, I would describe as an incremental opportunity. That's how we view it. I don't think the pipeline thesis for Incyte is trading on any one opportunity. And I do believe that the pipeline we have right now has the potential to support our target growth rate post 2029.

Now is it enough? If we execute, then the answer is yes. But as you know, these are probabilistic opportunities and attrition is a fact of life. And our job is to sort of keep this product line moving. We can't declare victory yet. Over the next 12 to 18 months, you will receive updates on many of these programs, at least Phase I updates as we're running the Phase III programs, and you will receive updates on how we are expanding each program, the initiation of studies and Pablo talked a great deal about our [indiscernible] oncology program at ESMO. And we'll provide you and everyone else with visibility into how we are advancing this pipeline so that there's more clarity on the growth potential of Incyte post '29 on top of the core business.

Operator

Our next question today is coming from Andrew Berens from Leerink Partners.

Andrew Berens

Congrats on all the progress. It's great seeing you guys in Madrid. I don't know about you, but I'm practicing by Spanish as an insurance policy against next week. Maybe a bit of color on the decision to deprioritize PRO for the CDK-2. We noticed there wasn't a focus at your event on Monday, but we thought really looked pretty good relative to some of the other oral programs in the same setting. Was it the trial wasn't enrolling well or something else that you saw? And then if I could just sneak in a little more on the MS program and the endpoints. I know you did give some color. But what's your sense of the regulatory buy-in for the potential to get a biomarker-driven endpoint eventually in the frontline setting? .

William Meury

Pablo will take the question.

Pablo Cagnoni

Thank you, Andy. Good to see you earlier this week. So it's the competitive landscape mainly. So look, we like 667, the dating communion we bev, as you saw and you pointed out, we thought looks pretty strong, 48% response rate in the late-line population. But the data that has continued to accumulate in platinum-resistant ovarion with ADCs convince us that, number one, the study will be very challenging to accrue; and number two, the commercial prospects in that indication were limited.

Now we continue to believe that there will be a role for an oral option for these patients, particularly in molecular targeted population. The maintenance study continues, and we do have a large data set in platinum-resistant disease that we'll discuss with FDA. Now I think the probability I said approval on that basis is very, very small because there's very clear evidence that, a, randomized trials can be running that disease; and b, the efficacy has been superior to what we've shown with 667 to be very frank. So that's the basis for discontinuing that one study.

On MF, look, I -- a surrogate biomarker import would be ideal. I don't think we're there. And I don't think we're there mainly because I'm not sure what that endpoint would be today. We talked about VAF and VAF is an interesting way to monitor, to some extent to progress. but it's far from an ideal endpoint because, as you know, VAF in peripheral blood measures a lot of cells that are not relevant to the treatment effect of 989 or any color antibody.

What we do believe, however, is that it's time in MF to consider alternative endpoints to SVR35 and TSS50. And that is incorporating different measures of normal hematopoiesis hemoglobin platelets as well as blast in peripheral blood as well as spleen volume, quite honestly, that is a better way to characterize the treatment response to a drug like 989 and it's also those factors are better predictors of long-term survival in MF patients that's simply using SVR35 and TSS50. That's why we want to continue that conversation with FDA.

Operator

Our next question is coming from Salveen Richter from Goldman Sachs.

Salveen Richter

Could you speak to what you'll share with regard to preclinical data for your next-generation antibody at ASH? And we should think about the profile of this asset versus 989 in competitors? And then also how you would position your bispecific given the similar pathway?

William Meury

Thanks for the question, Salveen. Go ahead, Pablo.

Pablo Cagnoni

Thank you, Salveen, and good to see you early this week. So based on -- let me make 2 points that I think are really important. Based on the preclinical data that has been disclosed by our competitors and the preclinical data that we have in hand, I think our next-generation mCALR antibody is the best-in-class CALR antibody out there. The reason for that is we've optimized every property that we thought we had to optimize on 989. This novel medicine is 70x more potent against known type mutations. And it has a much longer half life. You'll see the details at ASH.

But it will allow at least for monthly subcu injection, maybe even less frequent depending on what we see in patients. It will be subcu, obviously, from day one. We expect that the dose that's going to be required is going to fit in a pen. So we really believe that this will address some of the limitations that 989 has. And as excited as we are as getting approved 989 approved for patients with TNF, we think that this next gen will be very helpful in the longer run.

Just -- I know you didn't ask about that one, but we're also going to present data on the next-gen V617F inhibitor. We think this drug addresses a lot of limitations that we had with our previous entry in this space. So we look forward to sharing that data with you.

regarding bispecific, as we've discussed a couple of times over the past year, I need to see more data to understand exactly where the bispecific will be positioned in patients with the MF. Efficacy and safety will determine what kind of a role this medicine potentially can play in this disease. I think responsibly in patients with more accelerated MF that need a more rapid tumor reduction. But if the data with 989 continues to look better and better, one could argue that this space for the bispecific could become a little bit more limited.

Operator

Next question today is coming from Jay Olson from Oppenheimer.

Jay Olson

Congrats on all the progress. For 734, what are your plans for combination strategies in PDAC and CRC especially with the positive news from petosemtamab, how are you thinking about moving 734 into earlier lines in combination with petosemtamab?

William Meury

So the combination that we announced is, in fact, to study 734 in combination with petosemtamab and FOLFOX in patients with colorectal cancer. Obviously, you need to do a Phase I study first, but the idea is to move to frontline therapy as quickly as possible. We reviewed the landscape of novelty GFR inhibitors. We decided, and I think the data that was released yesterday confirmed that, that was the right choice. We believe that petosemtamab is the best next-generation EGFR inhibitor, and that's why we put that collaboration in place.

Operator

Our next question is coming from Ash Verma from UBS.

Unknown Analyst

This is [indiscernible] on for Ash. So I have one on the G12D program. Can you talk about your enrollment strategy for Phase III and fourth line PDAC. It seems like some of the other competitors are flagging the need to enroll from ex U.S. sites given increased new agents use in the front line. So what patients -- what percent of patients do you intend to enroll from U.S. as well as ex U.S.? And do you have agreement with the FDA on the enrollment mix?

Pablo Cagnoni

So it's an important question, and we looked at it in a couple of different ways. First of all, in terms of enrollment itself, it's going extremely well. So we have no concerns at this point. We're not going to yet provide an exact timing for completion of enrollment. But based on our initial projections, it's on track, if not a little bit of ahead of schedule. So that's going very well. No concerns there.

Now the question -- it's important to answer what happens if a lot of dexonrasib gets used in patients that progress and whether that treatment effect of [indiscernible] post progression is different in the 2 arms of the study. We've done extensive statistical modeling. We're going to track that in the study and we can potentially shift to countries where the [indiscernible] is not approved if we see that that's happening in a lot of patients.

I would say at this point, we already have more than enough patients enrolled in the U.S. to be sufficient for an FDA submission. So I have no concerns about not having enough U.S. patients. What we will monitor though is post progression of [indiscernible] use to make sure that, that does an impact the post progression of PFS 2 in a way in one or more than the other. And if there is a need for intervention, we will shift 2 countries with [indiscernible] is not approved.

Operator

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

Gavin Clark-Gartner

I just wanted to ask on the second-line MF mCALR study. Are there any limitations on the percent of patients that can receive a JAK inhibitor in the best available therapy arm? And what are your expectations for what that number will be? And just to clarify on the primary endpoint. So that's type 1 only. When you do hierarchical testing, do you go look in the ITT population? Or do you specifically then look in the nontype 1 population?

William Meury

No, there's no other mutation in the percentage of patients that can receive a JAK inhibitor. As you know, if you look at the data, one has to be careful to looking at studies that allow versus did not allow wash-out after prior line first-line therapy, the prior line therapy prior to enter in a second line study. So the SVR35 is as low as 8% in patients depending on whether they did or did not have wash-out. Our data that we presented at ASH, which is close to 40% SVR35 and about 40%, 45% TSS50 it's in patients with no washout that obviously are expected to do worse. So that's important to remember. So we have -- we feel very confident that all the approved therapies in second line are substantially inferior to what we've seen with 989 so far.

The only other comment I'm going to make about the statistical testing is that the primary endpoint is in type 1 patients. We thought that was the right way to run the study to ensure success and to get this medicine approved for these patients, which are about 2/3, if not a little bit higher of the patients with color mutations. We will collect the data in nontype 1 patients. Obviously, we'll have it available. But the primary analysis of the study is in type 1 disease.

Operator

Your next question today is coming from John Newman from Canaccord Genuity.

John Newman

Congrats on all the progress. You previously stated that at least at this point in time, you probably won't pursue combinations with your G12D and a pan-RAS inhibitor. I'm just wondering, outside of the work that you're doing with your G12D, have you considered at all licensing G12D [indiscernible], it seems like an area where there are a few competitors with maybe not quite as many yet as G12D?

William Meury

Great question. On the PAN RAS, we don't rule out doing a combination with the PAN RAS. We are continuing to scan the landscape to see if there is an option that is suitable for us. So we're not ruling it out. I mean be very clear. We've done preclinical work, and we think there's value in the combination. In terms of G12D, we are interested in expanding our KRAS franchise. So also, we would not rule out, at some point, addressing patients with G12D mutations.

Operator

Next question today is coming from Michael Schmidt from Guggenheim Securities.

Michael Schmidt

I just had another follow-up on 989. So thinking about the possible registration strategy in frontline MF patients, will the focus there also primarily be on type 1 patients with a 36 month endpoint? Or would that include a broader opportunity? And how will you presentation the next-gen CALR antibody relative to 989 in that context?

William Meury

On the first part, we'll see what the data takes us. Right now, we continue to develop 989 to try to address the needs of all patients with CALR mutations. We made a decision in second line as we just discussed. In frontline, the data will guide that decision. So let's talk after ASH, and then we can -- once we both have the data in front of us, we can see what that looks like. Now remember, a potential path in first line, as I discussed a few minutes ago, is a 3-arm study with Jakafi in combination with 988. In that case, that calculation might change a little bit. So let's keep that in mind as we review the data at ASH.

On the next gen, right now, the positioning is getting to as fast as possible, getting to pivotal trust as fast as possible. We think that if we reach an agreement with FDA on the starting dose, our current understanding of this target will allow us to have a very short dose escalation period. If you remember, 989, we had to start at 50 to 70 milligrams to escalate all the way to 2,500. That took a long time. It is not going to be the case with the next-generation program. We think we can get to the recommend the Phase II dose much faster. And our goal is to start pivotal trials with NextGen in 2028.

Operator

The next question is coming from Mitchell Kapoor from H.C. Wainwright.

Unknown Analyst

This is Amit on for Mitchell. I guess looking at 734 and DAWN-302, what's the [indiscernible] combo replacing secondhand chemo? And will that [indiscernible] second-line cohort be large established benefit independently of third line results?

William Meury

Let me see if I understand the question. So you're asking about the design of the 302 of the colorectal trial?

Unknown Analyst

Yes. I was just wondering if you will be able to distinguish the benefit in second line versus third line patients?

William Meury

Yes. It's a good question. In general, I expect -- let me put it this way. I expect that the study will enroll predominantly third-line patients because the control arm will allow [indiscernible] served bev which was the winning arm of the sunlight study as well as regorafenib of fruquintinib. And when you put those options in the control arm, you're more likely to end up with a third line shifted population. So whether the data at the end are sufficient for a broad label, time will tell, depends on the population we enrolled, depending on the results of the study. So based on the control arms, that's what we expect.

Now I wanted to this question to address one point also, which I think is very important about the DAWN-302 study just to make sure we're all clear on what the expectations are of the control arm. The Sunlight study had a PFS about 5.6 months, and that was cited by several as the benchmark. Importantly, in the Sunlight study, BEV-exposed patients had a PFS of 4.5 months. which is substantially lower. And DAWN-302 will be in BEV exposed patients. So we expect the control arm overall will underperform the overall Sunlight study.

The other point that's important is we run a real-world analysis with Tempus showing a Sunlight study population and patients with KRAS mutations do worse on [indiscernible] BEV than [indiscernible]. So based on that, we think the reassured or the probability of success of DAWN-302 is quite high considering the expectations for the control arm.

Operator

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

Jacob Goell

This is Jacob on for Derek. Can you just provide us some of your thoughts on label scenarios for Povo and HS? And what analogs do you could point to there for the launch?

William Meury

I think there are basic label scenarios. We studied both a pre- and post-biologic population. And so that would be clearly the preferred label scenario. The other is just simply a post-biologic population, and there are JAK inhibitors, for example, an AD that have an indication, different data set different indication post biologics. I think that they're both workable paths. I think the biggest opportunity for povacitinib is it can be used at both inflection points, a moderate to severe patient diagnosed with HS who has been only receiving antibiotics and steroids, which are imperfect solutions. That's a large pool of patients.

And then after a biologic for patients who have active disease aren't achieving consistent pain relief or a loss of response, which has been well documented, especially with TNF alpha. We're in discussions right now with the FDA. And as part of planning for this launch, we plan for both plausible outcomes. We've not seen the label. We expect that the data will support a broad label, but I'm laying out the range of possibilities.

And I'll let Mohamed comment on how to think about analogs?

Mohamed Issa

Yes. I think Bill really not much to add. I mean the analogs that we've seen so far will really dictate based on the data. And we believe we have a broad label that supports a broad indication and different analogs, I think, in the marketplace today, so just the same based on the data sets that were submitted in their pivotal program. So we'll wait and see. But like Bill said, I think the most important point is that both scenarios are very workable, and we're very optimistic about the opportunity.

Operator

Your next question is coming from Eric Schmidt from Cantor Fitzgerald.

Imogen Mansfield

This is Imogen on for Eric. Does the trial on clinicaltrials.gov for an antibody and MPN INTA036978 that started enrolling earlier this year as monotherapy and in combo with standard disease directed therapy. Could you just tell us a little bit about that program? And is it targeting CALR or something else? And then one question on POVO. In the mild to moderate HS population, we've heard very encouraging feedback from KOLs here if this ends up being a positive set of Phase III studies. Why do you think that peak sales could get to for Opzelura -- sorry, not for POVO, but for Opzelura and HS?

William Meury

Great. I'll turn over the first part of your question, Imogen, to Pablo? .

Pablo Cagnoni

Thank you for the question. At this point, we're not going to disclose the target. All I would say is that, that antibody is mutation-agnostic antibody for patients with MPN, so you can potentially target CALR as well as 617F as well as MIP mutations, and we'll disclose the actual target at the right time, Imogen. I'm sure you'll understand.

William Meury

And Image, I think your question was about Opzelura and HS. And I think the backdrop here is really important. There is no FDA-approved oral anti-inflammatory and there's no FDA-approved topical, now the study we did was in mild to moderate HS. And so there's some overlap with POVO, but not a lot. Our math is there's a couple of hundred thousand patients, roughly maybe 300,000 in that mild to moderate segment. And if you picked up 10%, 15% of that or more, it could be a 5% to 10% lift on Opzelura. We have to wait for the data in the fourth quarter but it could produce $50 million, $100 million in incremental sales, I think, is not a heroic assumption. We'll wait and see what the data looks like, and it will be a part of the growth story. It's not necessarily built into our models right now. We're just waiting for the data.

Operator

Our final question today is coming from Tara Bancroft from TD Cowen.

Srikripa Devarakonda

So I was hoping maybe you could tell us the time line to the clinic for 954, the V617F and what we should focus on in the preclinical data that's most indicative of potentially improve clinical profile versus 958?

William Meury

Certainly. So the entering the clinic for NextGen [indiscernible] 954 would be early 2027. We never disclosed the exact date, but it's going to be in the early part of 2027. The main things that we wanted to address here compared with our previous entry was improving the selectivity and important, in this case, to always remind ourselves that what matters is selectivity between wild-type and V617F mutated cells. This is not a JAK2 selectivity question is wild-type versus mutated cells.

And we've run extensive preclinical studies that you'll see at ASH, and we think the selectivity of this molecule is substantially better than our previous V617F inhibitor. So we feel much better about that.

The second is we work a formulation ahead of time. If you remember, we had to do a lot of work on the formulation of [indiscernible]. Now the formulation that we're going into the clinic, we feel much better about. So both the formulation side and the selectivity of the molecule and the margin in preclinical tox studies are much better than [indiscernible] 54. So we're really excited about moving this program forward.

Operator

We've reached the end of our question-and-answer session. And ladies and gentlemen, 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.