Incyte Corporation

Greetings and welcome to the Insight Second Quarter 2026 Earnings Conference Call and Webcast. At this time, all participants are in a listen-only mode. A question and answer session will follow a formal presentation. You may be placed into question queue at any time by pressing star 1 on your telephone keypad, and we ask you please limit yourselves to one question and then return to the queue. As a reminder, this conference is being recorded. If anyone should require operator assistance, please press star 0. It's now my pleasure to turn the call over to Alexis Smith, Vice President, Head of Investor Relations. Please go ahead, Alexis.

Thank you and good morning. Welcome to Insight's second 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 Suki, 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.

Thank you, Alexis, and good morning everyone. At the start of the year, we laid out a plan to move Insight from an alliance on a cornerstone product to a company with multiple growth drivers. Six months in, This transition is well underway and we've made tangible progress. We've strengthened the core business, delivered key regulatory milestones, de-risked and advanced our pipeline to late stage development, and added a novel phase three hematology asset through business development. Let me expand on each. First, our business continues to perform above expectations. Total net sales growth was driven by increased demand and higher net sales across every product. Jackify remains foundational to the company and delivered another strong quarter. Keeping this product healthy is a strategic priority because it serves as a funding vehicle for the pipeline and new product launches. At the same time, our core business, excluding Jackify, continues to grow and is solidly on track to reach three to four billion dollars in net sales by 2030. Importantly, this growth is not dependent on a single asset, but is supported by multiple products and near term launches. We have the commercial capabilities, resources, infrastructure, and management team required to execute successfully. The opportunity here is not simply the value of each individual product, but our ability to launch and scale multiple products in parallel. This capability will be a key driver of Insight's next phase of growth. Second, we achieved several of the key regulatory milestones we identified at the beginning of the year, including the approval and launch of JackifyXR, as well as the positive CHMP opinion of Opsalura in moderate AD with the final European Commission decision and signature expected in the third quarter. In addition, regulatory reviews for Povacitinib and HS and Monjuvian first-line DLBCL are underway with anticipated approvals and launches through early 2027. Third, we moved multiple assets into late stage development. We launched phase three studies for 989 and second line ET, 734 and PDAC, and 890 and CRC. We also have a catalyst for its second half of the year with 10 data readouts across nearly all assets in our clinical pipeline, including data from our registration trials for Opsalura, NHS, and porvacitinib and PN. As these programs advance, we are gaining greater visibility into the potential shape of our growth profile beyond 2029. We also strengthened our hematology portfolio through business development. The Vega transaction added latarsabart, a potentially transformative treatment for von Willebrand's disease in phase three development, and a potential new growth driver for the company. Latarsabart expands our most important therapeutic franchise, offers an attractive risk-reward profile, and the transaction was structured to preserve balance sheet flexibility. It checked all the boxes we look for in business development and is a textbook example of a type of deal that makes sense for Insight. Taken together, Insight is no longer dependent on one asset, catalyst or blockbuster. We now have a solid core business, a series of near-term launches and a more mature late-stage pipeline supporting multiple avenues for future growth. Operationally, we're a stronger organization than we were a year ago. Our focus right now is execution, turning phase three studies into approvals and approvals into successful launches. Turning to the quarter, total revenue in the second quarter of 26 was $1.67 billion, up 38% year over year. Total net sales in the second quarter were $1.49 billion, representing 40% growth year over year. The increase was driven by continued demand across the portfolio and by a one-time non-cash benefit from the CMS settlement. Excluding this benefit, total net sales increased 17%. This growth was broad-based with every marketed product growing year-over-year in both the U.S. and international markets. Jackify sales in the second quarter were $817 million, up 7% year-over-year. Prescription demand for Jackify increased 9% across all indications, MF, PV, and GVHD. with PV being the largest growth driver. New patient starts remain strong, the prescriber base is stable, and formulary coverage is broad, providing an important foundation for the Jackify XR launch. A few comments on XR. The launch has two parts, coverage and adoption. On coverage, we're on track to achieve our year-end formulary goal of 50 to 70%, supported by recent wins at ESI, CVS, Optum, and more than 10 regional plans. On adoption, we expect physician adoption to build gradually through the remainder of 2026 as coverage expands and physicians gain experience with XR, with acceleration expected throughout 2027. Commercially, XR generated 10 million in sales in the second quarter, which primarily consists of initial inventory build, We expect XR sales to approach $40 to $50 million for the full year, which is captured in our full year Jackify guidance. Sales for our core business, excluding Jackify, were $671 million, up 127% year over year, excluding the one-time Opsalura benefit. Sales grew 44%. This business is becoming an increasingly important part of how we transition Insight through the LOE period and for long-term growth. Opsalor remains the largest contributor of business outside of Jackify, generating $450 million in second quarter sales. This includes $204 million of net product sales and a one-time non-cash benefit of $246 related to our agreement with CMS and the reversal of previously accrued balances associated with the resolution of Medicaid rebate litigation. In the U.S., sales excluding the one-time benefit were $161 million, an increase of 22% versus the second quarter of 2025. Demand here remains strong, with prescriptions increasing 26% year-over-year, which outpaced the overall market, which grew 21%. New patient starts also remain strong, with Opsalura capturing 46% of branded topical NBRX volume, a leading indicator of future growth and business health. The resolution of the CMS matter improves the economics of the business, resulting in a favorable change to our average selling price and gross to net profile. It effectively offsets some of the investment we made to expand and maintain formulary access at the beginning of the year. As a result, prescription growth should translate more efficiently into net sales growth going forward. That said, we continue to view the pricing and reimbursement environment as dynamic, and so maintaining broad access and a disciplined gross to net profile remains a priority. Opsalura is in a stronger position today than it was a year ago. Demand is robust and access is broad. And while we're encouraged by this momentum, this is not a business we can put on autopilot. Sustaining growth will require effective commercial execution and continued focus on the access and pricing dynamics that support growth. Internationally, Opsalura sales were $43 million in the second quarter, up 34% year over year. Growth remains robust in Vitiligo where we see strong demand across markets. We remain on track for potential approval and launch of Opsalura for moderate atopic dermatitis in Europe during the third quarter. We expect modest revenue contribution in 2026 with momentum building through 27 as additional countries launch and reimbursement expands. We continue to view the international expansion of Opsalura as an important long-term growth driver for the franchise with the potential to deliver two to three times the international sales today. Finally, in hematology and oncology, net sales grew 69% to $222 million. Nictimbo, Monjuvi, Zainez were the biggest contributors to growth in the quarter. Nictimbo net sales were 60 million in the second quarter of 26, representing a 67% increase versus the prior year. The performance was entirely volume growth based. More than 300 new patients initiating therapy during the quarter, and more than 1,200 patients treated. We currently hold approximately one third of the third line plus market. Monjuvi net sales were 54 million in the second quarter, up 72% year over year. Growth was primarily driven by uptake in follicular lymphoma in international markets, including the recent approval and launch in Japan in the second quarter. Monjuvi is expected to have three sources of growth, relapse refractory, DLBCL, follicular lymphoma and potentially Firstline DLBCL. We expect the existing indications to remain incremental contributors while Firstline DLBCL has the potential to become the largest growth driver for the franchise over time. Finally, Zyna's net sales were 50 million in the second quarter, a four times increase year over year with rapid and robust adoption in SEAC across markets. In the U.S., Zyna is becoming the leading prescribed regimen with over a 40% share in Firstline SEAC in just 12 months post-launch. Now I'll turn the call over to Pablo.

Thank you, Bill, and good morning, everyone. At the beginning of 2026, we outlined ambitious development plans for the R&D organization, including four anticipated approvals, two new product launches, seven key data readouts, and the execution of 14 pivotal studies across our portfolio. As we have reached the midpoint of the year, I am happy to report that we have made significant progress and remain well positioned to deliver on the milestones we outlined. In the past 12 months, we have fundamentally changed the maturity of our portfolio, advancing multiple programs from early development into late stage clinical trials while delivering regulatory submissions and approvals. Today, we have late stage opportunities across all three of our core franchises. creating multiple opportunities for sustained long-term growth. All regulatory submissions supporting our four anticipated approvals for 2026 are now complete. Jackify XR was approved in the second quarter representing the first of our two new product launches planned for this year. In June, Opsalura received a positive CHMP opinion for the treatment of patients with moderate atopic dermatitis in Europe. with an approval anticipated in the third quarter. If approved, Opsalura would become the first topical JAK inhibitor treatment available in Europe for moderate AD. Our submissions for Provercitinib and Hadronatisuprativa and Tafacitamab in newly diagnosed diffused large B-cell lymphoma are under regulatory review with anticipated approvals and launches beginning later this year and into 2027. Beyond our regulatory progress, we deliver multiple important data readouts across hematology, oncology, and dermatology, including registrational data for tafacitimab in first-line DLBCL and povercidinib in vitiligo, as well as additional data for 989 in essential thrombocythemia and myelofibrosis. At the same time, we expanded our late-stage pipeline with additional latarcibar and have advanced 13 of our now 15 planned pivotal studies with the remaining two study initiations expected by year end. Our teams continue to execute well against our development priorities, positioning the portfolio for both near-term value creation and long-term growth. Importantly, many of our highest value catalysts, including data readout and regulatory decisions, remain ahead, positioning us for a catalyst-rich second half of the year. With that, I'll now turn to the pipeline. Our hematology strategy combines leadership in established disease areas with first-in-class mutation-directed therapies designed to redefine treatment across Grafer's-Rousseau's disease, myeloperiferative neoplasms, and now bleeding disorders with additional latar-sivart-forbund-willebrand disease. In chronic Grafer's-Rousseau's disease, we continue to advance exotilamab in two studies, evaluating its potential use earlier in the treatment paradigm, including in combination with ruxolitinib and in combination with steroids. We remain on track to share top line data from the phase two study in combination with ruxolitinib in the second half of 2026. Top line data from the phase three study with steroids is expected in early 2028. We're also advancing a portfolio of molecularly targeted therapies for myeloproliferative neoplasms or MPNs focused on the underlying driver mutations of disease. Our NPM strategy is built around targeting the underlying biology of disease through highly selected therapies directed against key disease-driving mutations, COL-R and JAK2V617F. Our portfolio includes 989, a mutant COL-R monoclonal antibody in late-stage development, 784, our COL-R by CD3 bispecific in an ongoing Phase I trial, and next-generation programs in preclinical development. We continue to evaluate emerging data as these programs progress and prioritize those we believe have the strongest profiles and greatest potential for patients. As part of this assessment, we decided to discontinue development 058, our lead asset in our JAK2V617F targeted pipeline, and are no longer expecting to report data later this year. Based on the totality of the data to date, we do not believe the molecule demonstrated the profile necessary to become a differentiated therapy. Importantly, this decision is specific to O5-8 and does not change our conviction in JAK2V617F as an important therapeutic target in MPNs. We are prioritizing our next-generation JAK2V617F targeted assets. We believe these next-generation programs provide a clear opportunity to realize the promise of selectively targeting JAK2V617F. These programs are progressing through IND-enabling studies and we'll plan to share more information, including preclinical data, by the end of the year. Turning to our most advanced MPN program, 9A9, the first and only mutation-specific therapy to enter late-stage development in cholera-mutated MPNs. Early in the quarter, at the European Hematology Association Annual Meeting, we presented additional Phase I data in mutant cholera-positive patients with ET and MF. As this data has matured, we continue to see evidence supporting the differentiated clinical profile of 999, strengthening our confidence in both the ongoing Phase III program and the broader development strategy in MF. As mentioned earlier, our Phase III study is now underway in mutant choleropalsity patients with ET who have received prior cytoreductive therapy. In MF, We remain on track to initiate a Phase 3 study in JAK-experienced patients in the second half of this year. We will provide an update following the completion of regulatory discussions. Additionally, we continue to advance our Phase 1 cohort, evaluating 9A9 as a first-line treatment for patients with MF, both as monotherapy and in combination with ruxolitinib. We expect to share data from this cohort along with additional data from the JAK ineligible cohort previously presented at EHA later this year. We also continue to advance the subcutaneous formulation of 9A9 and initiate a phase one study in mutant color palsy patients in the second quarter. In addition to ongoing efforts, we recently entered a global collaboration and license agreement with Halozyme to evaluate the subcutaneous formulation of 9A9 using enhanced technology. This collaboration complements our internal subcutaneous development efforts and provides additional flexibility as we optimize the administration profile of 9A9 for future commercial use. Earlier this month, we strengthened our hematology portfolio through the acquisition of Vega Therapeutics, adding Latarsibart, a novel prognosis modulator in Phase III development for patients with von Willebrand disease, to our late-stage pipeline. At the International Society of Thrombosis and Hemostasis Congress earlier this month, data from the multi-dose VIVID-3 study evaluated in latarcibar in patients with VWD were presented during a featured oral session. In VIVID-3, latarcibar demonstrated an 81% median reduction in annualized bleeding rate across patients with different von Willebrand disease subtypes and bleeding types, along with a favorable tolerability profile. With once-monthly subcutaneous dosing, latarciabart also has the potential to significantly reduce treatment burden compared with current prophylactic therapies, which are typically administered two to three times per week. Taken together, the efficacy, tolerability, and dosing profile combined with its novel mechanism of action give us confidence in the potential of latarciabart to establish a new standard of care. Our focus now is on advancing the Phase 3 VIVID-6 trial and we remain on track to deliver top-line data by early 2029. Turning to our oncology portfolio. All three of our lead solid tumor programs, 890, our TGF beta receptor 2 by PD-1 bispecific antibody, 734, our KRAS C12D inhibitor, and 667, our CDK2 inhibitor, are progressing through pivotal development, reflecting the continued maturation of our oncology pipeline. In parallel, we continue to generate data in robust Phase I programs exploring the potential of these acids across different indications, lines of therapy, and combination settings, which will help inform broader development efforts. At the European Society for Medical Oncology Congress in October, we plan to present four rapid oral presentations highlighting Phase I data across all three acids. This includes data for 734, in first-line pancreatic and late-line colorectal, 890 in first-line and late-line colorectal, and 667 in recurrent ovarian cancers. These presentations will represent the most comprehensive clinical update we have provided across our leading oncology programs and includes substantially larger and more mature datasets than we have previously shared, providing greater insight into the depth of the clinical efficacy and overall safety and helping further define the emerging competitive profile of each program. For 890 and 734, the presentations will include data in combination with chemotherapy and inpatient populations directly aligned with our ongoing Phase III studies. At the same time, the breadth of data across all three programs will help inform potential expansion into additional indications and treatment settings. Now I would like to turn to our IAI portfolio, where we continue to build a dermatology franchise across both topical and systemic therapies with multiple opportunities for continued expansion. Regular clinical efforts for ruxolitinib cream and povacitinib continue to progress. We remain on track to report top-line results from our Registrational Phase III program evaluating ruxolitinib cream in mild to moderate HS by year-end. If positive, this data could support the first topical therapy specifically developed for patients with HS and would further expand Opsilora's role across inflammatory skin diseases. For povercitinib, we continue to execute a broad development and regulatory strategy designed to support a multi-indication franchise. Povercitinib is under review for the treatment of moderate to severe HS and we expect potential approvals in Europe in late 2026 and in the U.S. in the first quarter of 2027. In the first half of the year, we share positive results from our Phase III program in vitiligo. Additionally, we remain on track to report top-line results from our Phase III program in prurigo nodularis in the fourth quarter. By year-end, we expect to have delivered six registrational study readouts for ruxolinib cream and poercitinib across HS, vitiligo, and PN. further strengthening our dermatology franchise spanning multiple diseases and treatment modalities. To close, we continue to make meaningful progress across our pipeline in 2026, delivering important clinical and regulatory milestones. Our portfolio is broader, more mature, and increasingly diversified and we expect an active second half of the year with multiple registrational data readouts, regulatory decisions, and developing milestones across our three core franchises that we believe will further strengthen our long-term growth trajectory. With that, I'll turn it over to Suki for a financial update on the quarter.

Thanks, Pablo, and good morning, everyone. I'll begin with comments on our second quarter results and then turn to our updated four-year outlook. As Bill mentioned earlier, total revenue in the second quarter was $1.67 billion, an increase of 38% driven by strong product sales. Total net product sales were $1,490,000,000 reflecting 40% growth versus the prior year. The increase was driven by strong product demand and a one-time non-cash benefit of $246 million. Excluding the one-time benefit, total net sales increased 17% versus the prior year. Total gap expenses for the quarter were $976 million, an increase of 42% compared to the prior year. The year-over-year increase reflects a lower expense base in the second quarter of 2025, resulting from the Novartis settlement of $242 million. When we exclude the favorable adjustment in the second quarter of 2025, total operating expenses grew 5%. Gap cost of goods was $105 million, representing 7% of total net sales. This is in line with our expectations, and we expect COGS to be between 8% to 9% for the full year. Our GAAP R&D expenses were $517 million, an increase of 4%, driven by continued investment in our late-stage development assets across hematology and oncology. Moving to GAAP SG&A, expenses were $352 million, increasing 6%, driven by pre-launch activities We ended the quarter with $4.5 billion in cash and cash equivalents. This includes the close of the Vega Therapeutics acquisition in July, which I'll provide more color on momentarily. Now turning to our outlook for the remainder of the year. We are updating several components of our existing guidance for the full year, including total net sales, which is driven by guidance updates to Opsalura, as well as hematology and oncology, and R&D and SG&A operating expenses, driven by the close of the Vega acquisition and related incremental costs in the second half of the year. Starting with net sales, we are raising our full year 2026 total net sales guidance to $5,130,000,000 to $5,260,000,000. For Opsalura, we are updating full year 2026 net sales guidance to $1,050,000,000 to $1,100,000,000. Our new guidance reflects the previous guidance of $750 to $790 million and the incremental estimated impact of $300 to $310 million of net sales related to the CMS settlement. This impact includes two key components. First is a one-time non-cash benefit of $246 million related to Opsalura net sales that was recorded in the second quarter. As a reminder, this amount is associated with the reversal of previously established accrual balances through the first quarter of 2026. Second, higher net sales from an improved gross to net profile in the second quarter through the fourth quarter. In the second quarter, the impact of U.S. Opsalura net sales was 15 million. This is a net impact after consideration of certain one-time prior year state-related liabilities that became effective at the conclusion of the CMS settlement. On a go forward basis, we expect the impact to be approximately 40 to 50 million for the second half of the year. Regarding our hematology and oncology portfolio, we are narrowing and raising full year guidance range to 860 to 890 million based on strong performance in the first half of the year. Turning to operating expenses, we are updating our full year 2026 operating expense guidance. We are narrowing and raising our 2026 GAAP R&D and SG&A operating expense guidance to $4,915,000,000 to $4,995,000,000. We are also raising total non-GAAP R&D and SG&A operating expenses to $4,625,000,000 to $4,695,000,000. The new guidance reflects an increase of approximately $1,270,000,000 related to the upfront payment for in-process research and development and associated transaction costs in tandem with approximately $50 million in ongoing phase three development of darsabart and von Willebrand's disease. To close, we are pleased with our performance for the quarter and for the first half of the year and remain confident in our outlook. With that, I'll turn the call back over to the operator for Q&A.

Thank you. And I'll be conducting a question and answer session. If you'd like to be placed into 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 2 if you'd like to remove your question from the queue. As a reminder, we ask you please ask one question and then return to the queue. Our first question today is coming from Mark Fromm from TD Cal and your line is now live.

Thanks for taking my questions and congrats on the strong quarter commercially. This is mostly for Pablo. Just on the Cal-R program, and your regulatory discussions. Can you maybe just review what the major questions are still kind of awaiting resolution on that trial design and MF? You know, how much of that is the endpoint, whether you can include something like anemia and some sort of composite versus, you know, how much of that is still outstanding dose selection work for particularly the type twos and might on that latter part that take a little bit longer for type ones versus type twos and lead to kind of different trial initiation timelines?

Good morning, Mark. Thank you for the question. So when we think about the regulatory path in MF, there's basically two paths, right? One would be the standard, which I think we all know about, which would include SVA-35 and TSS-50 as endpoints, or an alternative one, which will include other endpoints. Now, let me spend a minute on why we think the second is important to discuss with FDA. We thought and still think it's important to discuss with FDA. 989 presented a completely novel mechanism of action, as we all know. And on top of delivering benefit, as we saw in the EHA data update that we provided, on top of delivering benefit on SVR35 and TSS50, it delivers an extraordinary benefit on improving hemoglobin levels in these patients. Most of the patients treated, whether it's first or second line MF, show increases in hemoglobin that are clinically significant. In addition to that, there's clear evidence of what we discussed as disease-modifying evidence, including reduction of malignant myocarditis in the bone marrow, reduction of malignant progenitus in peripheral blood, et cetera. So when you put all that together, we thought and still believe it's important to have a constructive dialogue with the FDA to see how we can incorporate some of these endpoints that reflect the benefit patients receive from 9A9 and that reflect the mechanism of actual 9A9 that they need to be reflected in the clinical trial design. We have initiated those conversations with FDA. They're going well. They've been constructive. And as soon as we complete those, we will give you clarity on what the regulatory path will be, first and second line MF, which we intend to start this year. And then as a result of that, we'll continue the conversation with the agency on first line MF, which we will initiate next year. At this point, our intention is to conduct a study in MF in all comers, type 1 and non-type 1 patients, potentially with a differential dosing strategy. Not quite like in ET because in ET we have a dose escalation. The rapid normalization of platelets in ET allows you for a rapid dose escalation. In MF we would start type 1 and non-type 1 patients at two different dose levels instead of doing the dose escalation. That's where we are today with the planning of the study. Thanks for the question, Mark.

Thank you. Our next question today is coming from Eric Schmidt from Cancer Press Gerald. Your line is now live.

Thank you. Maybe a higher-level strategic question for Bill and team. Given you've just done the Vega acquisition, how are you feeling about the breadth and depth of your pipeline? Do you have more capacity, and is there some sort of a target R&D as a percent of sales level that you might want to be spending at as we go into the Jackify expiration? Thanks.

Yeah, it's a good question, Eric. A couple of things. As it relates to business development, and frankly R&D. Our job is to keep this product line and pipeline moving. And so I think you can never underestimate attrition in any business. And so we are actively looking at potential opportunities that meet or check the same criteria that Vega did. And I think that we have a very clear framework for doing business development. When we see opportunities that meet certain strategic and financial criteria, we can act quickly. Alternatively, if we don't, we're comfortable being patient. As it relates to R&D as a percentage of sales, I'd make a couple comments there. We're not pursuing growth one at all costs. Alternatively, or on the other hand, we're not solving right now for a fixed margin percentage. What I will tell you is if there's any margin compression in this business, let's say as we get to 2029, there'll have to be a clear and positive correlation with materially increasing the risk adjusted value of our pipeline. And right now every line item in our P&L is either absorbing, offsetting, or directly funding The growth strategy. As you know, in SG&A, we're funding product launches. And as it relates to R&D, 80% of our investment is concentrated on what we think are really smart investments. And if any of the investments that we're making, if the facts and circumstances around those investments change or performance is not what we are expected, we stop making those investments. And as we get closer, and we have more clarity on our pipeline where I think we're set up very well right now. I think when you look at the pipeline, there's four assets that have a high PTRS and the potential to deliver outsized returns. That's Povacitinib, 989, G12D and VGA 039. Now that's not to say that there's not value in TGF beta by PD1 or CDK2. But the four assets I just mentioned have the potential to move Insight way beyond Jackify, which is ultimately what we're solving for. And so, you know, to wrap it up, 12 months of margin compression to set up 10 years of revenue and earnings growth, I think is a smart calculation. And that's what we look at every day.

Thank you. Our next question is coming from Kazin Ahmad from Bank of America. Your line is now live.

Hi, good morning. Thanks for taking my question. I wanted to maybe ask one quick one about the announcement you made last week about your global collaboration with Halazine to use their enhanced drug delivery technology to help with 989. Can you maybe give us a little bit more color on what exactly you'd like to improve and when you think this could move into clinic and we can start to see Thanks.

Thanks, Azine. Pablo, why don't you set up where we are with the program overall and then give it to Halazan.

Certainly. I think, let me remind you of a couple of points that we've made, which are really important about this program and the sub-Q development. We have completed healthy volunteer work, and we are right now with the sub-Q, existing sub-Q formulation in patients with MPNs. That's the status of the program. We have a clear path here to continue that program forward and by optimizing the existing formulation and the existing subcutaneous device for infusion, which is not wearable. As we discussed before, this is something that patients will have to apply for 15 to 20 minutes every other week to deliver the desired dose. That path is clear. We have discussions with FDA on a bridging strategy for that path that I just described. We thought it was important to continue to add optionality to this program. As you can imagine, the conversations with Helizam have been going on for quite some time before signature of the agreement, and they're not related in any way to any data that has emerged from the ongoing subcutaneous development. We thought it was important to have an additional option to improve flexibility and potentially to improve the patient experience when it comes to subcutaneous Formulation Administration of 999. So that's basically the plan we have in place. We're executing the existing sub-Q plan with existing formulation, and we're adding another option now with the enhanced technology.

Thanks a lot for the question. Thank you. Our next question today is coming from Faisal Khurshid from . Hey, guys. Thank you for taking the question.

Can you set expectations for the G12D update that you're going to have at ESMO? and can you possibly give us some more perspective on how you think about competitive positioning and how you see your opportunity to differentiate within the class? Thank you.

Great. Pablo, you want to take the first part of the question?

Certainly. Thank you for the question. So, when we think about our 734, our G12D inhibitor, I think we are convinced we have in our hands a highly selective, highly potent Novel Medicine that combines well with existing standard of care, which is in first-time pancreatic cancer is chemotherapy, either Folfirinox or GemNap. In that context, when we think about the development plan, our goal was to accelerate as much as possible development in first-time pancreatic cancer in combination with those two chemotherapy regimens. What we will do at ESMO is provide approximately 50 patients' worth of data, half and half with GemNav and Folfirinox, with a fair amount of maturity, showing you where we are on efficacy and safety in that context. We think that's a really important deal risking for the first-line pancreatic cancer strategy that we're pursuing. Now, the phase three study in first-line pancreatic cancer is ongoing. As far as we know, based on public disclosures, we are We don't think we're behind and our team is executing on that as fast as possible. Now let me add a little bit more context on the program because I think it's important the breadth of how we're looking at this program in other indications. We're going to present data as well at ESMA of combination in colorectal cancer. We think that is a really important indication for G12D inhibitor. There's two basic ways to do it is late line in combination with EGFR inhibitors and in early lines in combination with chemotherapy and EGFR inhibitors. We'll show some of that data as well at the ESMO meeting. So when you start thinking about our G12D program, if things go well and the data that we present continues to do with the program, you should think about it in a number of different, in a couple of different tumor types and in a couple of different lines of therapy specifically. in pancreatic cancer in first line in combination with chemotherapy and potentially in the adjuvant setting as well, and in colorectal cancer in late line in combination with EGFR inhibitors and potentially in earlier lines in combination with chemotherapy and EGFR inhibitors. So we'll talk about it at ESMO. We think the data we're going to present is a significant de-risking event for this program in first line pancreatic and potentially in colorectal cancer as well. Thank you for the question.

I would just add to what Pablo said as it relates to competitive positioning. I think it's unlikely that pancreatic cancer becomes a winner-take-all market. You rarely see that in oncology. I think generally speaking, oncologists resist dependence on a single treatment. And so this is not, I believe, an either-or calculation. Populations are different. There's various combination strategies that can be put in place. I think at the end of the day, this will become about sequencing and matching the right drug with the biology. We believe a selective G12D inhibitor will be used first in G12D patients and then a non-selective later. But there again, it's not either or. And what we do know is there's only two companies right now in phase three studies with the first targeted G12D treatment in pancreatic cancer. And so whether you're first or early, This, for Insight, can be a real needle mover. And I think when you look at the data that we'll share at ESMO, you'll be reassured about the activity of this compound in terms of response rates as well as durability of response.

Thank you for the question. Our next question today is coming from Jay Olson from Oppenheimer. Your line is now live.

Oh, hey, congrats on all the progress, including closing the Vega deal. Based on everything you've learned, including feedback from KOLs at ISTH, can you comment on the potential for latarsabart to expand beyond VWD? And eventually, do you think latarsabart can be the next hemlibra? Thank you.

Jay, thank you for the question. I'm going to turn it over to Dave Gardner and let him make a few comments.

Yeah, thanks, Jay. Yes, we did get very favorable feedback, both from KOLs and, importantly, from the Patient Advocacy Channel as well at ISTH. A lot of the discussion was around the impressive clinical profile thus far from the Tarsabart. But a secondary discussion did emerge around the treatment of bleeds and the urgency to use better prophylaxis to prevent bleeds in a broader set of patients. So coming out of ISTH, absolutely, we are emboldened by the feedback that if we deliver on the target product profile, there is potential to deliver a transformative Hemlibra-like opportunity to these patients.

And Jay, if you think about it, there is a hemophilia A-like population in von Willebrand's. And that is a sizable pool of patients who are severe, frequent bleeders. And if O39 comes out of phase three, like David said, with a substantial reduction in the annual bleed rate and a good benefit risk profile, adoption in that group, which could be almost 10,000 people, would turn this into one of the largest products Insight would have. The most important thing for us to do right now is execute this phase three program, maintain the quality of the data, and then of course get it approved. But all of the substrate is there for this to be a large product. Thanks for the question.

Thank you. Our next question today is coming from Derek Archillo from Wells Fargo. Your line is now live.

Hey, good morning, and thanks for the update, and thanks for taking the questions. So, you know, given Nick Timbo's IPF data, Phase 2 data is going to come from CINDAC later this year. I know you guys have an opt-in, so just wondering if you could walk us through kind of the decision framework, you know, what sort of data thresholds may trigger an opt-in, how you kind of communicate that decision, and just remind us of the split on the development cost if you decide to proceed. Thanks.

Great. Thanks for the question.

Pablo? Yes, Derek, good morning, and thank you for the question. The disclosure of the data, since they're conducting the study, will be done by Syndex. It will not be done by us. Obviously, they'll share the data with us. We'll discuss the results, and depending how clear they are, it will take a little bit longer or not to make the decision to pursue the indication together with Syndex. When it comes to the existing agreement, it's the same type of agreement we have for other indications, both in sharing development costs and sharing economics. So there's no difference. And when it comes to the opt-in, I just want to make clear that if we decide to opt-in, there's nothing to prevent us from doing so. So we really look forward to hearing the data from our colleagues at Syndex, but they will be the ones releasing those results. Thanks for the question, Derek.

Thank you. Our next question today is coming from Andy Chen from Wolf Research. Why is that live?

Hi, thank you so much for taking my question. This is Jason taking it for Andy. And I just wanted to ask, how well is the Jakapa XR conversion tracking along your internal metrics so far? And do you know when payer reimbursement might kick in? And which specific earnings will this specifically impact the most? Thank you.

What was the second part of the question?

Oh, and one payer reimbursement might kick in, and which of the earnings coming up will this impact the most? Thank you.

Great. Thank you. Go ahead, Mohamed. Why don't you go ahead and comment on that?

Yeah, thanks, Bill and Jason. Thanks for the question. Look, like we mentioned earlier this year, we're focused on accelerating XR formulary access because that will serve as the basis for demand growth. and we're well on track to achieve that goal of 50 to 70% formulary coverage by the end of the year. So to answer your question specifically, when will payer reimbursement kick in? It has kicked in. And like Bill mentioned in the prepared remarks, several major payers have already moved and put XR on formulary. We've already seen demand start to pick up. And if by the end of the year, let's just say December, we exit the year with XR maybe representing somewhere between three to 5% of our demand, That'll put us somewhere in that $40 to $50 million range that Bill mentioned in their prepared remarks. And that puts us well on our way to that 10% to 30% conversion before Jackify LOE. So we're very pleased with the access so far. The market access team has done a really nice job of getting us and putting us in a position for demand generation to accelerate later in 2027. Thanks, Jason.

Thank you. Our next question today is coming from Matt Phipps from William Blair. Your line is now live.

Good morning. Thanks for taking my question. Nice execution in the quarter. Pablo, you mentioned the totality of the data did not support continuing to develop 058 for the V617F indication. Over the past year, it seems like the issue has really been around the bioavailability of this drug and being able to achieve target coverage. So were there other factors involved? as you change the formulation of things that contributed to this totality of the data. And can you just write us on the timeline for moving that backup program into the clinics and how you're thinking maybe about the internal program versus the prelude option? Thank you.

Certainly. Thank you. Thank you for the question. I think you captured the key point there. It was not just about bioavailability. It was not just about exposure. We think the new formulation showed promise and we will continue to escalate. When we started to look at the emerging data and what we look at, as you can imagine, is obviously the PK that you just pointed out to, as well as the safety and efficacy that it's emerging from a particular program. And we look at that in the context of other programs that we have in-house and that we have been advancing preclinically over the last couple of years. And when we put all that together, it just made no sense to continue to develop O5-18. The next generation programs have moved along very, very well. We're really excited about what the data looks like for clinically. We will provide an update for clinical data later this year, just so you have clarity on what the differences are between this program, this new program, and N058. And we're looking to basically follow the IND in the relatively near future. I won't give you a precise point in time right now, and we'll provide an update later this year when we present the data, but it's reasonably close to an IND filing. On the Prelude Agreement, obviously those programs are managed by Prelude. In terms of updates, they can provide them. The lead is in the clinic and there are other programs that we discussed with them that they're advancing through different stages of clinical development. We will sit down with them and discuss the current data that they have. but in terms of providing further updates on that, that should be done by Prelius and their programs at this point until we opt in.

Thanks for the question, Matt.

Thank you. Our next question today is coming from Evan Seegerman from BMO Capital Markets. Your line is now last.

Hi, guys. Thank you so much for taking my question. I want to touch back on some of the data at ESMA, specifically on 734. You know, as you prepared to present the PDAC and CRC data later this year, What benchmarks should we use to judge success? And how would you frame your conviction in this asset versus kind of the competitive profile that we had talked about earlier on this call? Thank you very much.

Thanks for the question, Evan. Pablo?

Certainly. So thank you for the question, Evan. So the way I think about it is as follows. So the first thing, we initiated a phase three trial in pancreatic cancer in combination with chemotherapy, as you know, with 734. and we've shown very little data other than ASCO GI last January. So we thought it was very important to have an expanded cohort of patients, as I mentioned, about 50 patients, about half and half with each type of chemotherapy with some maturity in order to de-risk this program and generate more conviction around that first-time indication. When you look at benchmarks, there's two sets of benchmarks here. One is existing chemotherapy, and that's pretty clear. There's a number of publications. with, you know, response rate into 30, 40, 45%. And then there are competitors which have presented some data as well in combination with chemotherapy. As we put the data at ESMO, we'll discuss it in more detail, but we think potentially we have a best-in-class agent here in combination with chemotherapy and frontline pancreatic cancer. We'll discuss those results and then, you know, hopefully we'll be the level, you'll share our level of conviction around that program. When it comes to colorectal cancer, obviously that's a smaller data set, but we'll have data in combination with Erbitux that we also think potentially starts to show signs of being a best-in-class agent to combine with an EGFR inhibitor in patients with colorectal cancer, which we think it might be an underappreciated opportunity for a G12D inhibitor that we intend to pursue.

Thanks for the question, Evan. Thank you. Our next question today is coming from Michael Schmidt from Guggenheim. Your line is now live.

Hey guys, thanks for taking my questions. I had one on the PD-1 TGF beta asset 890. Pablo, I guess what is your level of conviction that this could succeed in frontline colorectal cancer? How is that precision longer term in the CRC space relative to other emerging therapies, including amivantamab or ivanescimab, which are in phase three? And then how do you think about other opportunities for this age and longer term?

Thank you for the question, Michael. Okay, let's start with frontline colorectal cancer. What we know today is that TGF-beta receptor 2 by PD-1 antibody generated what I would describe as the best single-agent activity ever reported for a PD-1 therapy in patients with MSS colorectal, particularly in patients with liver metastasis. That led to An acceleration of that program, we generated that in combination with False Hooks Bev that first showed it was tolerable and they show increasingly a level of responses and durability that convinces that was the right path forward. So what we're going to show at ESMO is a pretty large data set with a fair amount of follow-up that we believe supports the frontline strategy with False Hooks Bev. We're fully aware of the competitive landscape. I think the difference here, and both approaches might work, Michael, but I think the difference is Bevacizumab is a very important drug in patients with colorectal cancer. And when you give a PD-1 by VEGF, you cannot give full-dose Bev. By giving a TGF interceptor 2 by PD-1, we can give it a full-dose Bevacizumab, which we believe could potentially be a differentiating feature. Data over time will decide which one of those approaches is better, and both might be successful. So that's point number one. The second is we've generated data also in combination with Bevacizumab alone. Some of the data might be presented at the meeting as well, and we believe also continues to show the potential of TGF-Better Center by PD-1 in colorectal cancer more broadly. When it comes to other tumor types, as you know, we've done some work in other tumor types. I'm not sure we're going to have time for an update on that at ESMO. We want to focus at ESMO on the three things that I discussed in my prepared remarks. G12D in pancreatic and colorectal, TGF-beta by PD-1 in colorectal, and 667 in patients with ovarian cancer now in combination with bevacizumab, which we also think it's an important update de-risking the maintenance study that we're conducting in that program.

Thanks, Michael. Thank you. Our next question today is coming from Jessica Five from KP Morgan. Your line is now live.

Hey, guys. Good morning. Thanks for taking my questions. Just wanted to confirm what the right way to think about Opsalura gross to nets is going forward. And also, can you just remind me of your regulatory plans for POVO in Vitiligo? Thank you.

Great, Jess. I'll take the first part of the question, and Mohamed or Suki can add. In simple terms, we were working with the gross to net in the low 60s, and with the settlement, Now we're in the high 50s. And as I had mentioned at the start of the call, it just simply improves the gross net profile and average selling price for Opsalora. You know, we made a strategic decision at the beginning of the year to expand access, and there was an investment associated with that. And I can tell you, here we are seven months later, and I think it was the right decision. Because when you look at the fundamentals of this business, which is basically volume growth coupled with coverage, were in a really good spot. Our job right now is to just manage this selling price as we get into 27 and 28. I think that pretty much covers it. And I think I can turn it over to Pablo or Steven to talk about the Vitiligo regulatory plan.

Thank you for the question, Jess. The plan in Vitiligo, after discussions we have with FDA over the past year or so, is to submit right after the approval in HS with two years of safety data, safety follow-up in the vitiligo patient. So basically as soon as the team is printing the filing, as soon as we get the HS and we sort of collect the two-year follow-up, we will submit that. So it's going to go in early next year.

Thanks, guys. Thank you. Our next question today is coming from Salvian Richter from Goldman Sachs. Your line is now live.

Thank you, good morning. Could you speak to your target profile for the MCLR program 989 as we look to first-line data by year-end in both the mono and combo cohorts versus what you've established with Jackify and the traditional endpoints of spleen and symptoms? And maybe put this in the context of the composite endpoint that you're trying to create as well. Thank you.

Great, thanks for the question.

Thank you, Sylvain. You know, as I mentioned, I won't repeat myself early in the call. You know, there's two regulatory paths here. One, traditional endpoints, as you allude, with SVR35 and TSS50, and the conversations we're having with FDA on second-line MF. Depending on the success of those conversations, some of those lessons may be applied to first-line MF or not. Our conviction here remains because of the data we presented in a small subset of JAK-ineligible patients. which is basically a JAK-NAE population which we present at AHA and we will update later this year. We show pretty solid numbers in terms of SVR35 and TSS50, stronger in type 1 patients than non-type 1, but certainly when you think about, if you remember the AHA data, there were very few non-type 1 patients that had received a higher dose. And we do know those patients do need a higher dose. So when you put all that together, Conversations with FDA will complete the second-line MF conversations. Depending on that and whether we are able to advance a different endpoint or not, we will decide the regular path for first-line MF. As of today, our plan continues to be in first-line MF to develop 999 both as a single agent and in combination with JICA5 and both in type 1 and non-type 1 patients. That's still the plan.

Thanks, Alvin.

Thank you. Our final question today is coming from Mitchell Kapoor from H.E. Wayne Wright. Your line is now live.

Hi, this is Medan from Mitchell. Thank you for taking our question. And I guess in the same vein, could you help the stage, set the stage for the 2H26 treatment naive MF lead out? What would support advancing 989 monotherapy versus plus roxalotinib or both? And how are you viewing the analysis of the incremental contribution of 989 in the combination arm?

Mitchell, could you just repeat the question? Your audio broke up.

Oh, yeah, no problem. I was just asking if you could help set the stage for the treatment-naive MF readout. What would help support the decision to advance 989 monotherapy versus a combination?

Oh, terrific. Thank you. Look, we have the JAK ineligible cohort from EHA. So that's the first data set that we have, which is about 20 patients that showed what I would describe as strong SVR35 and TSS50 data. And as I mentioned to Salveen, maybe we needed more data at the higher doses in non-type 1 patients to sort of complete the picture. Later this year, we'll have between 50 and 60 patients' worth of data with long follow-up, both in combination with Jackify and as a single agent that's a randomized, small randomized cohort and I think all that data put together is what's going to determine which path we go forward. Based on the emerging data that we have, our plan today is to develop 989 in frontline, both single agent and in combination, and both in type 1 and non-type 1 patients. But obviously the data that we're generating as we speak and that we'll provide an update on later this year will make the final determination there. Thanks for the question, Mitchell.

Thank you. That does conclude 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