Incyte Corp. Third Quarter 2026 Earnings Call - MORPHOSYS AG

Greetings and welcome to the Insight third quarter 2026 earnings call. At this time, all participants are in listen-only mode. A question and answer session will follow the formal presentation. You may be placed into question queue at any time by pressing star one on your telephone keypad. We ask you please ask one question then return to the queue. As a reminder, this conference is being recorded. If anyone should require operator assistance, please press star zero on your telephone keypad. 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. Good morning and welcome to Insight's third quarter 2026 earnings conference call. Before we begin, I encourage everyone to go to the investor section of our website to find the press release, related financial tables, and slides that follow today's discussion. On today's call, I'm joined by Bill, Pablo, and Suki, who will deliver our prepared remarks. Stephen, 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. Thanks, Alexis, and good morning, everyone. As we look at the first nine months of the year, we've made meaningful progress against a strategy we laid out for Insight. That strategy has two fundamental components, scaling the core business beyond Jackify 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 3 development, including a mutant Cal-R antibody for MPNs, a protein S modulator for von Willebrand's disease, a G12D inhibitor for pancreatic cancer, a TGF-beta by PD-1 bispecific antibody in colorectal cancer, CDK2 inhibitor provarian 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 zero, but increasingly the risk we are managing is execution risk, running high quality phase three 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 three themes. First, key business performance. Every product grew year over year. Jackify had another strong quarter with growth across all indications, and sales from our core business, excluding Jackify, increased 37% from prior year. Second, we achieved important regulatory milestones, including the approval and launch of Opsalora for moderate AD in the EU in the third quarter. In parallel, the NDA reviews for Monjuvi and frontline DLBCL and for Bacitinib 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 Opsalora and our hematology and oncology franchise, while Jackify remained a significant contributor. Jackify 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. jackify 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 three percent this was driven by both new and existing patients formulary coverage is expected to exceed 80 percent 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 Jackify business by 2029. Now to our core business, XJackify, which is one of the clearest indicators of transitioning the company. Net sales from our core businesses, excluding Jackify, were $490 million, representing a 30% increase versus prior year, reflecting contributions from key growth brands, namely Opsalora, Nick Timbo, Zionist, and Monjuvi. The growth across brands and geographies strengthens the outlook for the company as we see this business growing to $3 to $4 billion by 2030. Opsalar 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 Opsalura 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 Opsalar 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 25% on a pro forma basis. Importantly, prescription demand increased 24% across both atopic dermatitis and vitiligo. New patient starts, an important leading indicator, increased 26%. The strong third quarter results reflect the strategy we outlined at the beginning of the year, which include expanding the sales force, taking a more targeted approach with nurse practitioners and physician assistance, and improving access quality. We're seeing progress across all three of those areas. Internationally, Opsalura net sales were $47 million in the third quarter, up 5% year-over-year. Excluding the benefit from a prior year reversal related to a government rebate program, underlying sales increased approximately 20% year over year. Now, Vitiligo has been the foundation of our international business to date. Looking ahead, the approval of Opsalar for moderate atopic dermatitis in Europe represents the next phase of growth for the franchise. As the first JAK inhibitor approved for moderate AD in Europe, we expect adoption to build over time as reimbursement expands across Germany and additional European markets in mid-2027. Excluding the one-time U.S. CMS impact, we continue to expect the international business to represent approximately 20% of total Opsalor net sales for the full year. Finally, our hematology and oncology portfolio delivered net sales of $235 million, an increase of 38% versus the prior year. Dictimbo net sales were $67 million, and an increase of 47% versus prior year, and approximately 10% sequentially. We expect full-year sales to approach $250 million. Zinus net sales was $58 million, with an increase of 157% year-over-year. Uptake in the U.S. and international markets remains strong, and Zinus is the leading first-line treatment option and only FDA-approved first- line treatment and SCAC. Manjuvi net sales were $55 million, up 30% year over year, driven by follicular lymphoma uptake in the United States, and the launch of Manjuv in Europe and Japan following approvals in follicular lymphoma during the first half of the year. This performance reinforces our belief that we can build a substantial hematology and oncology business beyond Jackify. With that, I'll turn the call over to Pablo to review our R&D project. Thank you, Bill, and good morning, everyone. We're making meaningful progress across our pipeline. Programs that were in early clinical development last year are now in phase three registrational studies. Today, more than 10 pivotal trials are underway across hematogy, oncology, and inflammation autoimmunity, including several programs with the potential to be first-in-class medicines. It is important to highlight how we got here. Each decision has been driven by data. We advance programs where the evidence is clear and focus on the treatment settings that can offer the greatest opportunity for patients and physicians. This discipline, built into our discovery and clinical organization, gives us confidence that we can continue to deliver. Today, I will cover the progress we have made year-to-date and during the quarter and highlight what lies ahead. Starting with myeloproliferated neoplasms, or MPNs, our ambition is to develop molecularly targeted treatments for every patient with an MPN by the beginning of the next decade. These efforts are anchored by 9A9, our mutant cholera monoclonal antibody, and the first mutation-specific therapy in late-stage development for color-mutated MPNs. Last year, we presented the first clinical data in patients with color-mutated essential thrombocytemia and myofibrosis, which established a foundation for development strategy. Our registration program in second-line ET is underway, with site activation ongoing and the first patient treated during the third quarter. In second- line MF, we have had productive conversations with the FDA, including alignment on the Phase 3 Excalibur MF2 study. We expect to initiate the study by year-end. The Phase 3 randomized study will evaluate 9A9 against best available therapy in patients with cholera-mutated myelofibrosis who have previously received a JAK inhibitor. The study will enroll patients with both type 1 and non-type 1 cholera mutations with mutation-specific dosing informed by our Phase I experience. Nicoprimer endpoints are spleen volume reduction of at least 35% or SZR35 and total symptom score reduction of least 50% or TSS50 at week 36. 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 serpion, spleen, and symptoms, including improvements in hemoglobin, platelet counts, and blasts in peripheral blood. This allows us to further characterize the potential benefit of a disease-modifying therapy on key manifestations of MF. The study's power to evaluate efficacy in patients with type 1 mutations will represent more than 70% of the color-mutated MF population and have experienced the most robust clinical responses to date. We will also continue to generate data in patients in non-type 1 mutations to further characterize the potencial 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 help define the role of 989 in an early treatment setting and inform our development plans in 2027. Additionally, we plan to share preclinical data on our next-generation mutant cholera 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 MPN, we continue to advance important programs across our hematology pipeline. The FDA's review of tapacitumab and first-line diffuse large-speed 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 axotilumab in early lines of therapy. This includes a Phase II study of axotilimab in combination with ruxolitinib, with results expected at a medical meeting early next year, and a Phase III study evaluating axatilimab in combination of 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, latarcibar. This novel protein S modulator has the potential to be a transformative non-factor replacement treatment for von Willebrand disease. The pivotal phase 3 study is underway with top-line data expected in early 2029. We also plan to share additional data from the phase 1 open-level 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 KRSG12D inhibitor, our 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-induced 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 aducarcinoma, or PDAC, and in combination with Zitoximab in heavily pretreated patients with colorectal cancer. In PDAC 734 showed encouraging activity in combination we both standard of care chemotherapies with a safety and tolerability profile consistent with this established regimens. Objective response rates confirmed on pending were 58% for 734 plus gemcitabine and napoclitaxel, and 81% for 734-plus modififolfirinox. We also see promising signals of durability with six-month landmark PFS of 80% and 90% respectively. The death of response, early signs of durability, and consistent tolerability across both chemotherapy backbones reinforce our confidence in the ongoing Phase III DON303 study in first-line PDAC and support moving 734 into early stage of disease, with a phase 3 study in adjuvant PDAC planned to start in 2027. Turning to colorectal cancer, 734 in combination with cetuximab produced a 36% objective response rate in heavily protruded 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 3 DON302 study in previously treated coloreictal cancer. We reached alignment with the FDA in the design this quarter and plan to initiate this study in the first half of next year. Beyond these registrational programs, we recently announced clinical collaborations enabling evaluation of 734 with novel combinations. These include Pedocentamab, an EGFR by LGR5 bispecific antibody in first-line colorectal cancer, Neveli metastat, a PIMT5 inhibitor in PDAC, and SMB1521, a PARP1 inhibitor, in solid tumors. These Phase I studies will begin next year. Turning to 890, our TGA-PETA receptor 2 by PD-1 bispespecific antibody. We believe 890 has the potential to serve as an immunotherapy backbone. starting in microsatellites stable-call rectal cancer, or MSS-CRC, a disease that has historically been resistant to immunotherapy. At ESMO, we presented Phase I data evaluating A90 in combination with standard-of-care chemotherapy and first-line MSS CRC. A90, in combination mitofaltoxin 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 reduced responsiveness to immunotherapy. We also see early signals of durability with a six-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 A9-0 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 a more meaningful treatment option for patients and physicians. As a result, we're deprioritizing development efforts in platinum-resistant ovarial cancer. To open label Phase II Maestro I trial remains ongoing. However, we have made the decision to stop additional site activation and discontinue future enrollment in the randomized Phase III Maestra II 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 had 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. Turn to IAI, where we continue to build on our leadership in dermatology across topical and systemic therapies. In July, the European Commission approved Opsalura for adults with moderate atopic dermatitis, or AD. This approval makes Opsalura the first steroid-free topical JAK inhibitor available in Europe for this population and expands its EU label into a second indication. Povercidinib, 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 povercidinib in prurigo nodularis. Together, this program has positioned povercitinib for potential approval in multiple indications, including HS, PN, and vitiligo, building on the foundation Opsolura 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 Discover and clinical engine behind it, we're 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 Suki for a financial update on the quarter. Thank you, Pablo, and good morning. I'll begin with comments on our third quarter results and then turn to our updated four-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 gap expenses for the quarter were $2.27 billion, an increase of 146% compared to the prior year. This includes a $1,23 billion IPR&D expense related to the closing of the Vega acquisition. Total cash consideration for the transaction was approximately $1.27 billion, including $1-2.5 billion for the upfront. When we exclude the Vega-related IPR&D expense, total operating expenses for the quarter grew 12%. Gap 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 a quarter. Moving to SG&A, GAAP SG&a expenses were $364 million for the quarter, increasing 11% year over year, driven by pre-launch activities for povercitinib. 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 Jackify franchise of $3,220,000,000 to $3.270,000. 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 Jackify gross sales. We are raising our full-year guidance for Opsalura, hematology and oncology, and total net sales based on the strong performance delivered through the first nine months of the year. For Opsalura, we are raising full-year 2026 net sales guidance to $1,100,000,000 to $1120,000 million, reflecting continued growth in both the U.S. and international markets. For hematology and oncology, we're 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 $5,210,000,000 to $500,300,000. 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&B 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 nine 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. Thank you. We'll now be conducting a question and answer session. If you'd like to be placed into question Q, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question Q. You may press star 2 if you'd to like to move your question from the queue. As a reminder, we ask you to please ask one question and then return to the queue. Our first question is coming from Tazin Ahmad from Bank of America. Your line is now live. Hi, guys. Good morning. Thanks for taking my question. 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? Thanks. Thanks, Tazim. Pablo will take the question. Good morning, Tassin. Thank you for the question, Tash. So at ASH, we're going to present, as promised, an update on the first-line data. Now, just as an aside, you remember that at EHA, we presented data in patients that were ineligible for JAK-FI, and the data looked quite good, in our opinion, both in SBR35 and TSS50, as well as the anemia improvement that we've become accustomed to see in patients treated 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 front line. 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 eligible for JAKA-5. Those are split between single agent and a combination with ruxolitinib, about two-thirds, one-third approximately. And importantly, we have quite a bit of follow-up in those patients at this point. In fact, one of the things that 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 representation about four 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, that we wait for the data the presentation because that's a truly relevant data so i think it's a pretty comprehensive update i think you will give a clear idea of the role of 989 potential for online mf and we look forward to sharing the data with you thanks for the question to zine thank you next question today is coming from etzer darut from parkland germany is that live good morning this is gustav on for My question is on the second line, MS pivotal for 989. How will prior JAK inhibitor treatment be defined? Would the patient need to be resistance, refractory, or intolerant? And is there a minimum duration of treatment or dose for those? Thank you. DR. Go ahead, Pablo. DR. Thank you for the question. The definition is pretty standard in the fact that patients don't achieve ideal SVR35 or ideal spleen or symptom response to JAK-FI, or usually the reason for intolerance is the thrombocytopenia or anemia in most patients. So the physicians make that determination. There's no language in the protocol, but the physicians will make that determine and there's no minimum duration. I don't believe, I would have to confirm with the product, I don' believe there's any minimum duration of treatment of dose of JAKFI. Did those which occupy prior to entering a second-line study is now predetermined in a second line study at all? Thank you for the question. Our next question today is coming from Jessica Five from J.P. Morgan. Your line is now live. Hi, this is Sylvia on for Jess Five. Thank you. Thank you so much for taking our question. Can you elaborate on the strength that you are seeing in Opsalura, and are you able to quantify the growth to net you saw this quarter and how that differed from third quarter 25? Thank you. Yeah, it's a good question. I'll make a few comments and then Pablo, I mean, Mohamed can expand on them. You know, at the start of the year, we made a very deliberate strategic decision to expand the sales force, increase promotion to MPs and PAs, and to improve access quality, which required an investment. And if you look at the results this quarter, you focus on two 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. Opsalura has a very large prescriber base of 20,000 physicians. we have extensive formulary coverage, and we have probably north of a quarter of a million people receiving Opsalura today. And so that is a mode 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 a third of our core business extractify when we hit the transition in 2029. And, you know, Mohamed and his team have done an excellent job managing this product for the past, you know, several quarters. Mohamed, do you want to add anything? Yeah, maybe just to quantify a few of the points that you mentioned, Bill. Thank you. 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 buy 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 brand's 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. Yeah, and Sylvia, just to add one thing to what Mohamed just said, when you think about price for Opsalora, 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 Opsalor. Thanks for the question. Thank you. Next question today is coming from Salim Syed from Mizzou. Your line is now live. Hi. This is Eric on for Saleem. Congrats on the quarter and thanks for taking our question. One on axotilumab and GVHD. It looks like the first line AXA plus RUX readout got pushed out from 4Q26 to 1Q27. Just curious about the puts and takes on that and how that is How are you thinking about the overall timeline on that at this point, if that's different? Thanks. Thanks for the question, Eric. Pablo will take it. So the reason for that is simply to present the data. It's 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. and we want to show you durability of the response. We want to shows you subsequent therapy, a comprehensive review of the safety profile. So we want present that at a meeting, a scientific meeting, and the most appropriate one is in the first quarter of 2027. That's the only reason for shifting the timeline a little bit. Thanks for the question. Thank you. Our next question today is coming from Brian Abrams from RBC Capital Markets. Your line is now live. Hey there. Good morning. thanks for taking our question, and congrats on the continued progress. Maybe one on 989. I guess I'm curious, what 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 calorimutated patients, just given the known benefits of Jackify, but also the known AEs? Thanks. Great. Go ahead, Pavel. 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 two pieces of data to finalize the design of a frontline study in MF. First of all, let's go back to a comment I made a few minutes ago. We know from the EHA data in ineligible patients that the efficacy of 9A9 untreated, Ruxin-treated patients with MF is substantial. You all remember the SVR35 and TSS50 data that we showed, and the really striking effect on an EMA 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 Jackify, 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, as we are, 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 megakarycins 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 JAKA5 produces rapid improvement in symptoms and an SBR35 in commutative patients in front line 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 three-arm study, which would be RUX versus RUx plus 989 versus 989 alone. That's a perfectly legitimate study. Patients and physicians will have two 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. Thanks for the question, Brian. Thank you. Next question today is coming from Evan Siegerman from BMO Capital Markets. Your line is now live. Hi, guys. Thank you so much for taking my question. Great to see you earlier this week. So just taking a step back, the pipeline progress that Insight has accomplished over the past year has been impressive. Can you just level set, kind of remind us what you've accomplished over this year the past year? And then looking forward, aside from MCLR at Ash, what are some things that we should be focused on over the next year so that when we get to the 3-2 call, we can discuss those as well? Thank you all. Yeah, 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 has 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 delivery incremental but reliable growth over time. More specifically, we have six assets right now in phase three. They're not all equal when you think about them on a sort of risk adjusted value basis. Pobacitinib, 989, 12D, and latarsabar 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 three or four 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 Insight 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, I think the answer is yes but as you know these are these are probabilistic opportunities and attrition is a fact of life um and our job is to sort of keep this product line moving uh 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 one updates as we're running the phase the phase three 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 GI oncology program at ESMO. And we'll provide you and everyone else with visibility into how we're advancing this pipeline so that there's more clarity on the growth potential of Insight post-29 on top of the core business. Thanks for the question, Evan. Thank you. Our next question today is coming from Andrew Behrens from Learing Partners. Your line is now live. Well, congrats on all the progress. It was great seeing you guys in Madrid. I don't know about you, but I'm practicing my Spanish as an insurance policy against next week. Maybe a bit of color on the decision to deprioritize P-ROC for the CDK, too. We noticed it wasn't a focus at your event on Monday, but we thought it 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 MF program and the endpoints. I know you did give some color, but what's your sense of the regulatory buy-in or the potential to get a biomarker-driven endpoint eventually in the frontline setting? Thanks. Thanks, Andy. Pablo, take the question. Thank you, Andy, good to see you earlier this week. So it's the competitive landscape mainly. So, look, we like 667, the dating community with Bev, as you saw and you pointed out, we thought looks pretty strong, you know, 48% response rate in the late line population. But the data that has continued to accumulate in platinum-resistant ovarian cancer with ADCs convinces 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 this patient, particularly in a 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 of accepted approval on that basis is very, very small because there's very clear evidence that, A, randomized trials can be run in 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, a surrogate biomarker endpoint would be ideal. I don't think we're there. And I don' think we' re there mainly because I' m not sure what that endpoint would be today. You know, we' ve talked about VAF, and VAF is an interesting way to monitor, to some extent, the 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 blasts in peripheral blot, as well, a spleen volume, quite honestly, that is a better way to characterize a treatment response to a drug like 989, and it's also those factors are better predictors of long-term survival in MF patients than simply using SVR35 and TSS15. That's why we want to continue that conversation with FDA. Thank you. Our next question is coming from Salvina Richter from Goldman Sachs, trobitis now lies. Thank you. Good morning. Could you speak to what you'll share with regard to preclinical data for your next generation antibody at ASH and how 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? Thank you for the question, Salvin. Go ahead, Pablo. Thank you, Selvin. Good to see you early this week. So based on, let me make two points that I think are really important. Based on the preclinical data that has been disclosed by our competitors and the precinical data we have on hand, I think our next generation of cholera antibody is the best in class cholera antibodies out there. The reason for that is we've optimized every property that we thought we had to optimize on 999. This novel medicine is 70 times more potent against non-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 sub-Q injection, maybe even less frequent, depending on what we see in patients. It will be sub-q, 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 99 approved for patients with ET and MF, 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. Regardless, by specific, as we've discussed a couple times over the past year, I need to see more data to understand exactly where the bispecific will be positioned in patients with MF. Efficacy and safety will determine what kind of a role this medicine potentially can play in this disease. I think possibly in patients we more accelerate MF that need a more rapid tumor reduction. But if the data with 989 continues to look better and better, one could argue that the space for the bispecific could become a little bit more limited. Thanks for the questions, Al. Thank you. Next question today is coming from Jay Olson from Oppenheimer. Your line is now live. Oh, hey, congrats on all the progress, and thanks for taking the question. For 734, what are your plans for combination strategies in PDAC and CRC, especially with the positive news from petosemtomab? How are you thinking about moving 734 into earlier lines in combination with pentacentamab? Thank you. Thank you, Jay. So the combination that we announced is, in fact, to study 734 in combination with pentocentamib and Folfox in patients we call rectal cancer. Obviously, you need to do a phase one study first, but the idea is to move to frontline therapy as quickly as possible. We reviewed the landscape of novel EGFR inhibitors. We decided, and I think the data that was released yesterday confirms that that was the right choice. We believe that paracetamol is the best next-generation EGF-R inhibitor, and that's why we put that collaboration in place. Thank you. Our next question is coming from Ash Verma from UBS. Your line is now live. This is Paracos on for Ash. Thank you for taking our question. So I have one on the G12D program. Can you talk about your enrollment strategy for Phase 3 and fourth-line PDAC? It seems like some of the other competitors are flagging the need to enroll from ex-US sites given increased new agents use in the front line. So what patients, what percent of patients do you intend to enroll for from US versus ex-U.S.? And do you have agreement with the FDA on the enrollment mix? Thank you. Thanks, Ash. 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. You know, we're not going to yet provide an exact timing for completion of enrollment, but based on our initial projections, it is on track, if not, a little bit ahead of schedule. So that is going very well. No concerns there. Now, the question, it's important to answer what happens if a lot of Dioxin Rassive gets used in patients that progress and whether that treatment effect of Dioxid Rassiv post-progression is different in the two 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 Dioxid Rassif 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 direction of RASF use to make sure that that doesn't impact the post-progression of PFS2 in a way in one arm more than the other. And if there is a need for intervention, we will shift to countries where direction of RASV is not approved. Thank you. Our next question today is coming from Gavin Clark-Kartner from Evercore ISI. Your line is now live. Hey, guys. 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 non-type 1 population? Thank you. Thank you, Gavin. No, there's no limitation 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 washout after prior line, first line therapy, the prior line therapy prior to entering a second line study. So the SDR35 is as low as 8% in patients, depending on whether they did or did not have washout. Our data that we presented at ASH, which is close to 40% SDR 35 and about 40, 45% TSS 50, is in patients with no washout that obviously are expected to do worse. So that's important to remember. So we feel very confident that all the approved therapies in second line are substantially inferior to what we've seen with 999 so far. The only thing in common 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 two-thirds, if not a little bit higher, of the patients with cholera mutations. We will collect the data in non-Type 1 patients. Obviously, we'll have it available, but the primary analysis of the study is in Type 1 disease. Thanks, Gavin. Thank you. Next question today is coming from John Newman from Kennecourt Genuity. Your line is now live. Thanks for taking my question, and 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 G12-D, have you considered at all licensing a G12V as in Victor? It seems like an area where there are a few competitors, but maybe not quite as many yet as G12B. Thanks. 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's an option that is suitable for us. So we're not ruling it out. Let me be very clear. We've done preclinical work, and we think there's value in the combination. In terms of G12V, we are interested in expanding our KRAS franchise. So, also, we would not rule out, at some point, addressing patients with G12V mutations. Thank you. Next question today is coming from Michael Schmidt from Gruggenheim Securities. Your line is now live. Hey, thanks for taking my questions. I just had another follow-up on 989. So, thinking about the possible registration strategy in frontline MS 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 position the next-gen color antibody relative to 989 in that context? Thanks. Thank you, Michael. 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 color mutations. We made a decision in second line, as we just discussed. In front line, 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 three-arm study with JAKA-5 in combination with 989. In that case, that calculation might change a little bit. So, let's keep that in mind as we reviewed the data at ASH. On the next gen, right now, the positioning is get into a grant as fast as possible, get into 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, and we're going 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 recommended phase two dose much faster, and our goal is to start pivotal trials with next gen in 2028. Thanks, Michael. Thank you. Next question is coming from Mitchell Kapoor from HCWainwright. Your line is now live. Hi, this is Ahmed Khan from Mitchell. Thank you for taking our question. I guess looking at 734 and DON302, what's the poor 734 and cetuximab combo replacing second-line chemo? And will DON3022 second-land cohort be large enough to establish benefit independently of third-line results? Thank you. Let me see if I understand the question. So you're asking about the design of the 302 of the colorectal trial? Yeah, I was just wondering if we'll be able to distinguish the benefit in second-line versus third-line patients. Yeah, it's a good question. In general, I expect, let me put it this way, I suspect that the study will enroll predominantly third- line patients because the control arm will allow long-served BEV, which was the winning arm of the sunlight study, as well as regorafenib or frequentinib. 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. It depends on the population we enroll, depending on the results of the study. So based on the control arms, that's what we expect. Now, I wanted to, you know, do this question to address one point also, which I think is very important about the DON302 study, just to make sure we're all clear on what the expectations are of the control arm. The sunlight study had a PFS of about 5.6 months, and that was cited by several as the benchmark. Importantly, in the sunlight study, BEV-exposed patients had a PFAS of 4.5 months, which is substantially lower. and DON302 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 that the sunlight study population and patients with KRAS mutations do worse on long-served BEV than patients that are wild-type. So based on that, we think the reassurance that there's probably a success of DOM 302 is quite high considering the expectations for the control arm. Thanks for the question. Thank you. Our next question today is coming from Derek Archulik from Wells Fargo. Your line is now live. Morning, and thanks for taking our question. 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 we can point to there for the launch? I think there are two 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, in AD that have an indication, different data set, different indication. post-biologic. I think that they're both workable paths. I think the biggest opportunity for povercitinib 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. Yeah, I think, Bill, really not much to add. I mean, the analogs that we've seen so far will really dictate, you know, based on the data. And we believe we have a broad level that supports a broad indication. and different analogs, I think, in the marketplace today suggest 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. Thanks for the question. Thank you. Next question is coming from Eric Schmidt from Cancer Pistole. Your line is now live. Great. Hi. Good morning, everyone. This is Imogen on for Eric. there's a trial in clinicaltrials.gov for an antibody in MPN's INCA 036978 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 the program and is it targeting CALAR 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 three studies. Why do you think that peak sales could get to you for Opsalura? Sorry, not for POVA, for Oksalura in NHS? Great. I'll turn over the first part of your question, Imogen, to Pablo. 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 a mutation-agnostic antibody for patients with MPN, so he can potentially target COL-R as well as 617F as well as MIPL mutations, and we'll disclose the actual target at the right time, Imogen. I'm sure you'll understand. And Imogen, I think your question was about Opsalora and HS, and I think the backdrop here is really important. There's 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 hundred thousand patients, roughly, maybe 300,000 in that mild to moderate segment. And if you picked up 10% to 15% of that or more, it could be a 5% to 10% lift on Opsalura. We have to wait for the data in the fourth quarter. But it could produce, you know, $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'll be, you Know, a part of the growth story. It's not necessarily built into our models right now. We're just waiting for the Data. Thanks for the question. Thank you. Our final question today is coming from Tara Bancroft from BD Cal, and your line is now live. Hi. Good morning. Thanks for taking my question. So, I was hoping maybe you could tell us the timeline to the clinic for 954, the V617F, and what we should focus on in the preclinical data that's most indicative of potentially improved clinical profile versus 958. Thanks so much. Certainly. So the entry of the clinic from next-gen V615F-954 will 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 cell activity, 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 JAK1, JAK2 selectivity question. It's wild-time versus mutated cell. 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 inhibitors, so we feel much better about that. The second is we worked the formulation ahead of time. If you remember, we had to do a lot of work on the formulation of I4. Now the formulation that we're going to enter the clinic, we feel much better about. So both the formulation side and the selectively of the molecule and the margin in preclinical talk studies are much better than 054, so we're really excited about moving this program forward. Thanks for the question, Tara. Thank you. 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.