Q3 2025 Incyte Corp Earnings Call

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Greetings and welcome to the insight third quarter 2025 earnings conference call and webcast. At this time all participants are in a listen only mode.

A question and answer session will follow the formal presentation.

If you place into question queue at any time by pressing star one on your telephone keypad. We ask you. Please limit yourself to one question and one follow up then return to the queue. If anyone should require operator assistance. Please press star zero on your telephone keypad. As a reminder, this conference is being recorded its now my pleasure to turn the call over to Alexis Smith, Vice President and head of.

Speaker #3: One of these things were done with the video .

Speaker #2: Greetings and welcome to the insight . Third quarter 2020 Earnings Conference Call and Webcast . At this time , all participants are in listen only mode .

Alexis Smith: Greetings and welcome to the Incyte third quarter 2025 earnings conference call and webcast. 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 the question queue at any time by pressing Star 1 on your telephone keypad. We ask you please limit yourselves to one question and one follow-up, then return to the queue. If anyone should require operator assistance, please press Star 0 on your telephone keypad. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Alexis Smith, Vice President and Head of Investor Relations. Please go ahead, Alexis.

Speaker #2: A question and answer session will follow the formal presentation . You may be placed in the question queue at any time by pressing star one on your telephone keypad .

Investor Relations. Please go ahead Alexis.

Thank you good morning, and welcome to insights third quarter 2025 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 Tom will deliver our prepared remarks Steven.

Speaker #2: We ask that you please limit yourself to one question and one follow up , and return to the queue . If anyone should require operator assistance , please press star Zero on your telephone keypad .

Speaker #2: As a reminder , this conference is being recorded . It's now my pleasure to turn the call over to Alexis Smith , Vice President and Head of Investor Relations .

Speaker #2: Please go ahead , Alexis .

Dave Nick Halen Mohammed will also be available for Q&A I'd 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 will now hand, the call over to Bill.

Speaker #4: Thank you . Good morning , and welcome to INCYTE CORP third Quarter 2020 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 .

Operator: Thank you. Good morning and welcome to Incyte's third quarter 2025 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 Tom, who will deliver our prepared remarks. Stephen, Dave, Mateo, 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 will now hand the call over to Bill.

Speaker #4: On today's call , I'm joined by Bill , Pablo and Tom , who will deliver our prepared remarks . Stephen . Dave , Matteo and Muhammad will also be available for Q&A .

Thank you Alexis and good morning, everyone on our last call I told you I'd be taking a fresh look at the company with a focus on getting the core business right, our R&D priorities right and our cost base right.

Speaker #4: I would like to point out that we will be making forward looking statements , which are based on our current expectations and beliefs .

Speaker #4: 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 .

Of course, as a continuous process and one that is well underway and on track.

In terms of the core business. My assessment is reinforce my confidence in the growth potential of our key products as we announced today, we had a strong quarter with total revenues of 1.3 dollars 7 billion and product sales of 1.15 billion. This represents a 20% and 19% increase respectively versus prior year.

Speaker #4: I'll now hand the call over to Bill .

Speaker #5: Thank you , Alexis , and good morning , everyone . On our last call , I told you I'd be taking a fresh look at the company with a focus on getting the core business right .

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

Speaker #5: Our R&D priorities right and our cost base right . This , of course , is a continuous process and one that is well underway and on track .

The fundamentals around Jakafi obsolete, Ora and our hemo business, Nick Timberland mound jewelry, namely remains strong our job right now is to keep it that way and to identify effective ways to optimize the promotional strategies and investment for these products to drive future growth.

Speaker #5: In terms of the core business . My assessment has reinforced my confidence in the growth our key products . As we announced today , we had a strong quarter with total revenues of 1.37 billion and product sales of 1.15 billion .

Speaker #5: This represents a 20% and 19% increase , respectively , versus prior year . The fundamentals around Jakafi Opzelura and our business and Monjuvi , namely , remain strong .

Jakafi Q3 sales reached $791 million, a 7% increase with strong demand growth of 10% year over year growth was broad based across all three indications and MF Jakafi utilization continues to increase and we are maintaining market share leadership despite competition growth in <unk>.

Speaker #5: Our job right now is to keep it that way and to identify effective ways to optimize the promotional strategies and investment for these products to drive future growth.

Hervé Hoppenot: Our job right now is to keep it that way and to identify effective ways to optimize the promotional strategies and investment for these products to drive future growth. Jakafi Q3 sales reached $791 million, a 7% increase with strong demand growth of 10% year over year. Growth was broad-based across all three indications in MF. Jakafi utilization continues to increase, and we are maintaining market share leadership despite competition. Growth in GVHD remains strong, supported by our portfolio strategy with Naktimvo, which is helping identify patients across multiple lines of therapy, and PV is our largest growth driver fueled by compelling MAGIC-PV data showing impressive thrombosis-free survival. Based on this momentum, we're raising our full-year guidance for Jakafi to a new range of $3.05 billion to $3.075 billion.

<unk> HD remains strong supported by our portfolio strategy with Nick timber, which is helping identify patients across multiple lines of therapy. In PV is our largest growth driver fueled by compelling magic PV data showing impressive thrombosis free survival.

Speaker #5: Jakafi Q3 sales reached $791 million , a 7% increase with strong demand growth of 10% year over year . Growth was broad based across all three indications in MF Jakafi utilization continues to increase and we are maintaining market share , despite competition , growth in GVHD remains strong , supported by our portfolio strategy with Nick , which is helping identify patients across multiple lines of therapy and PV is our largest growth driver , fueled by compelling magic PV data showing impressive thrombosis free survival .

Speaker #5: Jakafi Q3 sales reached $791 million , a 7% increase with strong demand growth of 10% year over year . Growth was broad based across all three indications in MF Jakafi utilization continues to increase and we are maintaining market share , despite competition , growth in GVHD remains strong , supported by our portfolio strategy with Nick , which is helping identify patients across multiple lines of therapy and PV is our largest growth driver , fueled by compelling magic leadership potential of Based on this momentum , we're raising our full year guidance for Jakafi to a new range of 3.05 billion to 3.75 billion .

Based on this momentum we are raising our full year guidance for Jakafi to a new range of $3 5 billion to $3 75 billion.

After Lora growth was exceptional in the third quarter and continues to be a significant contributor to revenue.

With $188 million and sales of 35% increase versus prior year.

Of this 144 million in net sales came from the U S, which represented a 21% increase versus prior year. The increase was based on strong prescription demand across both indications and more favorable formulary placement at the three top pbms.

Speaker #5: Opzelura growth was exceptional in the third quarter and continues to be a significant contributor to revenue , with $188 million in sales , a 35% increase versus prior year .

Hervé Hoppenot: Opzelura growth was exceptional in the third quarter and continues to be a significant contributor to revenue with $188 million in sales, a 35% increase versus prior year. Of this, $144 million in net sales came from the U.S., which represented a 21% increase versus prior year. The increase was based on strong prescription demand across both indications and more favorable formulary placement at the three top PBMs. In July, we reorganized the Opzelura sales force into two dedicated sales teams, one for AD and one for vitiligo, to ensure execution and sustained growth. The market for branded non-steroidal topicals continues to expand at a 20% rate as more patients migrate off and away from topical corticosteroids. Given the efficacy of Opzelura in terms of rapid itch relief and skin clearance, our broad prescriber base, and formulary coverage, we're well positioned to take advantage of this market dynamic.

In July we reorganize the absolute sales force into two dedicated sales teams one for a D and one for vitiligo to ensure execution and sustained growth.

Speaker #5: Of this , 144 million in net sales came from the US , which represented a 21% increase versus prior year . The increase was based on strong prescription demand across both indications and more favorable formulary placement at the three top PBMs .

The market for branded non steroidal topical continues to expand at a 20% rate as more patients migrate off and away from topical corticosteroids.

Speaker #5: In July , we reorganized the Opzelura sales force into two dedicated sales teams , one for AD and one for vitiligo . To ensure execution and sustained growth .

Given the efficacy of ops of Lora in terms of rapid itch relief in skin clearance or broad prescriber base and formulary coverage, we are well positioned to take advantage of this market dynamic.

Speaker #5: The market for branded non-steroidal topicals continues to expand at a 20% rate as more patients migrate off and away from topical corticosteroids . Given the efficacy of opzelura in terms of rapid itch relief and skin clearance .

Internationally sales were up so Laura in vitiligo totaled $44 million, representing 117% increase from last year.

France, Spain, Italy, and Canada account for over 80% of our sales and growth and.

Speaker #5: Our broad prescriber base and formulary coverage were well positioned to take advantage of this market dynamic. Internationally, sales for vitiligo totaled $44 million, representing a 117% increase from last year.

And we plan to file an application for rux cream in moderate <unk>.

In the EU by year end with a potential approval in the second half of 2026.

Hervé Hoppenot: Internationally, sales for Opzelura in vitiligo totaled $44 million, representing a 117% increase from last year. France, Spain, Italy, and Canada account for over 80% of our sales and growth, and we plan to file an application for ruxolitinib cream in moderate atopic dermatitis in the EU by year end with a potential approval in the second half of 2026. Now in its third quarter post launch, Naktimvo continues to outperform expectations across all launch metrics. Sales in the third quarter totaled $46 million, an increase of 27% versus the second quarter. 90% of BMT centers have adopted Naktimvo, with all centers placing repeat orders year to date. Importantly, 80% of patients who started treatment in the first quarter of launch are still on therapy today, and we've captured 13% of the third line plus GVHD opportunity in just the first nine months on the market.

Now in its third quarter post launch Nick timber continues to outperform expectations across cross all launch metrics sales in the third quarter totaled $46 million, an increase of 27% versus the second quarter <unk>.

Speaker #5: France , Spain , Italy and Canada account for over 80% of our sales and growth , and we plan to file an application for Ruxolitinib cream in moderate ad in the EU by year end , with a potential approval in the second half of 2026 .

90% of BMT centers have adopted Nick timber with all centers, placing repeat orders year to date.

Importantly, 80% of patients who started treatment in the first quarter of launch are still on therapy today.

Speaker #5: Now , in its third quarter post-launch , Nik Timbo continues to outperform expectations across across all launch metrics . Sales in the third quarter totaled $46 million , an increase of 27% versus the second quarter .

We've captured 13% of the third line plus gvhd opportunity in just the first nine months on the market.

In line with expectations, Nick timber was primarily being used in the fourth line with increasing preference and utilization in the third one.

Speaker #5: 90% of BMT centers have adopted Netinfo , with all centers placing repeat orders year to date . Importantly , 80% of patients who started treatment in the first quarter of launch are still on therapy today , and we've captured 13% of the third line plus GVHD opportunity in just the first nine months .

Feedback from BMT centers has been positive with real world efficacy and safety being equally as impressive as the clinical data.

Finally, we're actively studying the timberland in combination with Rux Lytton had been steroids in earlier line settings are combination study with Jakafi is designed to enable a steroid free regimen in gvhd, which could shift the standard of care and our combination study with steroids in the frontline setting has the potential to deliver benchmark efficacy.

Speaker #5: On the market , in line with expectations . Nick Timbo was primarily being used in the fourth line with increasing preference in utilization in the third line , feedback from BMT centers has been positive , with real world efficacy and safety being equally as impressive as the clinical data .

Hervé Hoppenot: In line with expectations, Naktimvo is primarily being used in the fourth line with increasing preference and utilization in the third line. Feedback from BMT centers has been positive, with real-world efficacy and safety being equally as impressive as the clinical data. Finally, we're actively studying Naktimvo in combination with ruxolitinib and steroids in earlier line settings. Our combination study with Jakafi is designed to enable a steroid-free regimen in GVHD, which could shift the standard of care, and our combination study with steroids in the frontline setting has the potential to deliver benchmark efficacy and steroid tapering. This franchise strategy has the potential to significantly increase our addressable market and strengthen our leadership position in GVHD. Our broader hematology and oncology portfolio also performed well this quarter.

<unk> steroid tapering.

Speaker #5: Finally , we're actively studying Nick , Timbo and combination with ruxolitinib and steroids in earlier line settings . Our study with Jakafi is designed to enable a steroid free regimen in GVHD , which could shift the standard of care and are combination study with steroids in the frontline setting has the potential to deliver benchmark efficacy and steroid steroid tapering .

This franchise strategy has the potential to significantly increase our addressable market and strengthen our leadership position in gvhd.

Our broader hematology and oncology portfolio also performed well this quarter sales from on Juvie in Follicular lymphoma, and Zain as in SEC Both launch this year saw a strong growth and contributed to our raised guidance.

Speaker #5: This franchise strategy has the potential to significantly increase our addressable market and strengthen our leadership position in GVHD. Our broader hematology and oncology portfolio also performed well this quarter.

These products will be incremental contributors to our portfolio and collectively can deliver meaningful sales growth over the next several years.

We have three important new product launches next year <unk> <unk> in Europe and <unk>.

Speaker #5: Sales for Monjuvi and follicular lymphoma and Zynyz and Scac , both launched this year , saw strong growth and contributed to our raised guidance .

Hervé Hoppenot: Sales from Monjuvi in follicular lymphoma and Zynyz in SCAC, both launched this year, saw strong growth and contributed to our raised guidance. These products will be incremental contributors to our portfolio and collectively can deliver meaningful sales growth over the next several years. We have three important new product launches next year: ruxolitinib XR, Opzelura AD in Europe, and povorcitinib in HS. I've completed a thorough review of the launch plans and believe these products have the potential to contribute significantly to Incyte's future growth strategically. Ruxolitinib XR, upon approval, offers the same therapeutic benefits of Jakafi and a more convenient once daily dosing regimen. The stability data are on track to be submitted to the FDA before end of year with an anticipated launch in mid-2026.

NHS I've completed a thorough review of the launch plans and believe these products have the potential to contribute significantly to insights future growth strategically.

Speaker #5: products will be These incremental contributors to our portfolio and collectively can deliver meaningful sales growth over the next several years . We have three important new product launches next year Ruxolitinib XR , Opzelura AD , in Europe and Perversity and Ares .

Strategically <unk> upon approval offers the same therapeutic benefits of Jakafi in a more convenient once daily dosing regimen. The stability data are on track to be submitted to the FDA before end of year with an anticipated launch in mid 2026.

Speaker #5: I've completed a thorough review of the launch plans and believe these products have the potential to contribute significantly to InSight's future growth . Strategically .

As it relates to <unk> as mentioned, we plan to submit our application in the EU with an anticipated launch next year, assuming approval <unk> has the potential to contribute meaningfully to future sales in the EU, four and Canada and to overall growth given its clinical and economic value proposition.

Speaker #5: Ruxolitinib XR , upon approval , offers the same therapeutic benefits of Jakafi and a more convenient , once daily dosing regimen . The stability data are on track to be submitted to the FDA before end of year , with an anticipated launch in mid 2026 .

With the moderate 80 indication in Europe, we could potentially increase our international topical business by two to three X over the next several years.

Speaker #5: As it relates to AD, as mentioned, we plan to submit our application in the EU with an anticipated launch next year.

Hervé Hoppenot: As it relates to Opzelura AD, as mentioned, we plan to submit our application in the EU with an anticipated launch next year assuming approval. Opzelura has the potential to contribute meaningfully to future sales in the EU4 and Canada and to overall growth given its clinical and economic value proposition. With the moderate indication in Europe, we could potentially increase our international topical business by 2 to 3x over the next several years. Finally, povorcitinib could be the first oral option for patients with HS, which is perhaps the most challenging disease in dermatology. It's a multi-cytokine disease involving many pathways, making treatment more complex and results more variable. A treatment option like povorcitinib, which has shown rapid pain relief and skin clearance scores of over 50%, will be very marketable. We believe there's a substantial opportunity in HS, which is the first step for povo.

And finally poker sitting it could be the first oral option for patients with Hs, which is perhaps the most challenging disease in dermatology, it's a multi cytokine disease involving many pathways, making treatment more complex and results more variable a treatment option like <unk>.

Speaker #5: Assuming approval . Opzelura has the potential to contribute meaningfully to future sales in the EU for and Canada , and to overall growth .

Speaker #5: Given its clinical and economic value proposition . With the moderate AD indication in Europe , we could potentially increase our international topical business by 2 to 3 x over the next several years .

Which has shown rapid pain relief and skin clearance scores of over 50% will be very marketable we believe there's a substantial opportunity in Hs, which is the first step for provost our ongoing developments in pn and be a lot that are legal will come into focus next year and if positive further strengthen the position of provost and our <unk>.

Speaker #5: And finally , AB could be the first oral option for patients with HHS , which is perhaps the most challenging disease in dermatology .

Speaker #5: It's a multi-cytokine disease involving many pathways , making treatment more complex and results more variable . A treatment option like AB , which is shown rapid pain relief and skin clearance scores of over 50% , will be very marketable .

Folio to kept together with absolute era, we could provide a topical to oral offering for patients across Hs vitiligo and pn.

Speaker #5: We believe there's a substantial opportunity in HHS , which is the first step for Povo . Our ongoing developments in MN and V vitiligo will come into focus next year , and if positive , further strengthen the position of povo and our derm portfolio to , together with Oxaluria , we could provide a topical to oral offering for patients across his vitiligo and MN launch activities for each product .

Launch activities for each product remain on schedule, including preparations for the sales force payer engagements and medical education initiatives will share more details in early 2026.

Hervé Hoppenot: Our ongoing developments in PN and vitiligo will come into focus next year and, if positive, further strengthen the position of povo in our derm portfolio. Together with Opzelura, we could provide a topical to oral offering for patients across HS, vitiligo, and PN. Launch activities for each product remain on schedule, including preparations for the sales force, payer engagements, and medical education initiatives. We'll share more details in early 2026. Turning to R&D, our ongoing pipeline review is providing us with absolute clarity about which high-value programs are core to future growth and have the greatest potential to create value and outsize returns. We want to configure a balanced pipeline that is not consumed by either safe low-value projects or moonshots. We've set clear go/no-go criteria for moving key projects forward. We will invest and take calculated risks in key programs rather than thinly spreading investments across many programs.

Turning to R&D, our ongoing pipeline review is providing with providing us with absolute clarity about which high value programs are core to future growth and have the greatest potential to create value and outsized returns.

Speaker #5: Remain on schedule , including preparations for the Salesforce payer engagements and medical education initiatives . We'll share more details in early 2026 . Turning to R&D , our ongoing pipeline review is providing us providing us with absolute clarity about which high value programs are core to future growth and have the greatest potential to create value and outsized returns .

Want to configure a balanced pipeline that has not consumed by either safe low value projects or moon shots, we've said.

Clear go no go go criteria for moving key projects forward, we will invest and take calculated risks and key programs rather than thinly spreading investments across many programs in other words fewer smarter investments versus the few spending will fund what matters and importantly watch out for false positive.

Speaker #5: We want to configure a balanced pipeline that is not consumed by either safe , low value projects or moonshots . We've set clear .

<unk> and negative <unk>.

Speaker #5: Go , no go go criteria for moving key projects forward . We will invest and take calculated risks in key programs rather than thinly spreading investments across many programs .

As it relates to our developing pipeline.

The first call on capital is hemo. This is a central identity of the company and an area, where we have differentiated knowledge and capabilities and an asymmetrical advantage. This includes targeted therapies for mpls, including <unk> $6, seven or <unk> by specific and discovery programs, we have a window of opportunity here to trigger and <unk>.

Speaker #5: In other words , fewer , smarter investments versus diffuse spending . We'll fund what matters and importantly , watch out for false positives and negatives as it relates to our developing pipeline .

Hervé Hoppenot: In other words, fewer, smarter investments versus diffuse spending. We'll fund what matters and, importantly, watch out for false positives and negatives as it relates to our developing pipeline. The first calling capital is hemonc. This is the central identity of the company and an area where we have differentiated knowledge and capabilities and an asymmetrical advantage. This includes targeted therapies for MPNs, including CALR617, our CALR bispecific, and discovery programs. We have a window of opportunity here to trigger an innovation-based shift in MPNs from nonspecific symptomatic therapies like Jakafi and HU to targeted mutation-specific therapies like 989. Next steps for 989 and 617 will be shared later this year and next year.

Innovation based shift in mpls from nonspecific symptomatic therapies, like Jakafi and <unk> to targeted mutation specific therapies like 989.

Speaker #5: The first call on capital is Hemonc. This is the central identity of the company and an area where we have differentiated knowledge and capabilities and an asymmetrical advantage.

Speaker #5: This includes targeted therapies for mpns , including mikkeller six one seven , our MK bispecific and Discovery programs . We have a window of opportunity here to trigger an innovation based shift in mpns from non-specific symptomatic therapies like Jakafi and Hugh to targeted mutation specific therapies like 989 .

Next steps for <unk> hundred 89, and 617 will be shared later this year and next year.

In terms of our solid tumor program. The cornerstone of our cancer strategy is novel biological pathways high incidents cancers with substantial medical need that missed the Io Revolution, and Immunotherapies and targeted therapies that can be used frontline in combination with standard of care regimens.

Speaker #5: Next steps for 989 and 617 will be shared later this year and next year . In terms of our solid tumor program , the cornerstone of our cancer strategy is novel biological pathways , high incidence cancers with substantial medical need that missed the I o revolution and immunotherapies and targeted therapies that can be used frontline in combination with standard of care regimens .

As you know we have three programs in early development <unk> 12 D for pancreatic cancer TGF beta by PD, one by specific by specific for MMA, MSS, CRC and CDK to for ovarian cancer.

Hervé Hoppenot: In terms of our solid tumor program, the cornerstone of our cancer strategy is novel biological pathways, high-incidence cancers with substantial medical need that missed the IO revolution, and immunotherapies and targeted therapies that can be used frontline in combination with standard of care regimens. As you know, we have three programs in early development: KRASG12D for pancreatic cancer, TGFβR2 by PD-1 bispecific for MSS colorectal cancer, and CDK2 for ovarian cancer. Over the next several months, we will collect more data on these programs in terms of response rates, duration of response, and safety, particularly in combination with standard of care. We'll move forward without delay, provided our data continue to be objectively competitive and we can be early to market and defend our position long term.

Over the next several months, we will collect more data on these programs in terms of response rates duration of response and safety, particularly in combination with standard of care will move forward without delay providing our data continued to be objectively competitive and we can be early to the market and defend our position long term.

Speaker #5: As you know , we have three programs in early development Kras , for pancreatic cancer , TGF beta by PD one , bispecific bispecific for CRC , and Cdk2 for ovarian cancer .

Now in terms of our operating expenses and overall cost structure, we're conducting a review of the entire business, which focuses on prioritization and data driven trade off decisions.

Speaker #5: Over the next several months , we will collect more data on these programs . In terms of response rates , duration of response and safety , particularly in combination with standard of care .

Our objective is to manage costs, but not underfund critical initiatives and compromise growth prospects, we'll strike the right balance between financial discipline and long term strategic investments, which can be achieved by controlling costs and low value areas to free up capital either for reinvestment and high value opportunities.

Speaker #5: We'll move forward without delay, provided our data continue to be objectively competitive, and we can be early to market and defend our position long term.

Speaker #5: Now , in terms of our operating expenses and overall cost structure , we're conducting a review of the entire business , which focuses on prioritization and data driven trade off decisions .

Hervé Hoppenot: Now, in terms of our operating expenses and overall cost structure, we're conducting a review of the entire business which focuses on prioritization and data-driven trade-off decisions. Our objective is to manage costs but not underfund critical initiatives and compromise growth prospects. We'll strike the right balance between financial discipline and long-term strategic investments, which can be achieved by controlling costs in low-value areas to free up capital either for reinvestment in high-value opportunities or to improve margins. Our framework for the 2026 budget and beyond will be based on the following: first, define and ring-fence our strategic growth drivers. This means the new product launches that I touched on as well as key R&D projects which we have earmarked as non-negotiable, fully funded programs. Once we protect the growth drivers, we're looking to control costs in areas that add less or minimal strategic value.

Or to improve margins are.

Speaker #5: Our objective is to manage costs , but not underfund critical initiatives . And compromise growth prospects . We'll strike the right balance between financial discipline and long term strategic investments , which can be achieved by controlling costs and low value areas to free up capital , either for reinvestment in high value opportunities or to improve margins .

Our framework for the 2026 budget and beyond will be based on the following.

First define and ring fence, our strategic growth drivers. This means the new product launches that I touched on as well as key R&D projects, which we have earmarked is non negotiable fully funded programs.

Once we protect the growth drivers were looking to control costs in areas that add less or minimal strategic value.

Speaker #5: Our framework for the 2026 budget and beyond will be based on the following . First , define and ring fence . Our strategic growth drivers .

From there the savings we've identified and achieved will either be reallocated or banked. This will be a continuous process not a one and done exercise, it's a mindset as our business evolves, so will our resource allocation.

Speaker #5: This means the new product launches that I touched on , as well as key R&D projects , which we have earmarked as non-negotiable , fully funded programs .

Finally business development BD works when you have strong strategic leadership high throughput and a framework for rapidly triaging opportunities and making decisions, which requires a skilled search and evaluation team and a deep network to be successful we need to operate inside the loop and our focus areas Accordingly, Dave Gardner.

Speaker #5: Once we predict the growth drivers , we're looking to control costs in areas that add less or minimal strategic value . From there , the savings we've identified and achieved will either be reallocated or banked .

Hervé Hoppenot: From there, the savings we've identified and achieved will either be reallocated or banked. This will be a continuous process, not a one-and-done exercise. It's a mindset. As our business evolves, so will our resource allocation. Finally, business development, BD, works when you have strong strategic leadership, high throughput, and a framework for rapidly triaging opportunities and making decisions, which requires a skilled search and evaluation team and a deep network. To be successful, we need to operate inside the loop in our focus areas. Accordingly, Dave Gardner joined Incyte as Chief Strategy Officer in September, and one of his priorities is to build out this capability. He will play a central role in developing our long-term growth strategy and ensuring external business development opportunities and internal portfolio decisions are strategically sound and financially compelling. We will share more details about our strategic review early next year.

Speaker #5: This will be a continuous process , not a one and done exercise . It's a mindset . As our business evolves , so will our resource allocation .

Joined insight as Chief strategy Officer in September and one of his priorities is to build out this capability he.

Speaker #5: Finally , business development BD works when you have strong strategic leadership , high throughput and a framework for rapidly triaging opportunities and making decisions , which requires a skilled search and evaluation team and a deep network to be successful , we need to operate inside the loop in our focus areas .

He will play a central role in developing our long term growth strategy and ensuring external business development opportunities and internal portfolio decisions are strategically sound and financially compelling we will share more details about our strategic review early next year now.

Speaker #5: Accordingly , Dave Gardner joined Insight as chief strategy Officer in September and one of his priorities is to build out this capability . He will play a central role in developing our long term growth strategy and ensuring external business development opportunities and internal portfolio decisions are strategically sound .

Now I'd like to turn the call over to Pablo.

Thank you Bill and good morning, everyone.

As shown on slide 14, our pipeline is strategically focused with numerous high impact programs currently in development.

Over the past few months, we have conducted a thorough pipeline review to ensure we're concentrating our efforts and resources on the projects that are essential to the future growth of the company.

Speaker #5: And financially compelling . We will share more details about our strategic review early next year . Now , I'd like to turn the call over to Pablo .

Hervé Hoppenot: Now I'd like to turn the call over to Pablo.

As Bill mentioned this process was guided by a clear set of go no go criteria, enabling us to make strategic decisions about which programs to advance as a result, we have decided to pause or stop several preclinical and early clinical stage programs, including <unk> 34, 460, our anti CD 122 program.

Speaker #6: Thank you , Bill , and good morning everyone . As shown on slide 14 , our pipeline is strategically focused with numerous high impact programs currently in development .

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

Speaker #6: Over the past few months , we have conducted a thorough pipeline review to ensure we're concentrating our efforts and resources on the projects that are essential to the future growth of the company .

IMC be $5 76 for three our bet inhibitor program and the development of polar Sydney and chronic spontaneous urticaria.

Speaker #6: As Bill mentioned . This process was guided by a clear set of go no go criteria , enabling us to make strategic decisions about which programs to advance as a result , we have decided to pause or stop several preclinical and early clinical stage programs , including Inca 34460 .

By continuing to streamline our pipeline, we will be able to accelerate and prioritize the programs with the greatest potential impact to patients and to drive future growth.

Speaker #6: Our anti-CD122 program, INCB 57643, our BET inhibitor program, and the development of Palbociclib and chronic spontaneous urticaria. By continuing to streamline our pipeline, we will be able to accelerate and prioritize the programs with the greatest potential impact to patients and to drive future growth.

Now I'd like to focus on key updates from the quarter, highlighting recent advancements with <unk> and our solid tumor franchise.

We'll also discuss what's expected for the remainder of 2025 from our mutant call our antibody program.

Proposed sitting here last month, we presented longer term data in hidradenitis Suppurativa at the European Academy of Dermatology, and Vinnie Rheology Congress, which further reinforced the differentiated profile of power sitting there.

Hervé Hoppenot: To drive future growth.

Speaker #6: Now , I'd like to focus on key updates from the quarter , highlighting recent advancements with positive and our solid tumor franchise . I will also discuss what's expected for the remainder of 2025 from our Mutant caller Antibody program .

Pablo Cagnoni: Now I'd like to focus on key updates from the quarter highlighting recent advancements with povorcitinib and our solid tumor franchise. I will also discuss what's expected for the remainder of 2025 from our mutant CALR antibody program for povorcitinib. Last month we presented longer term data in hidradenitis suppurativa at the European Academy of Dermatology and Venereology Congress, which further reinforced the differentiated profile of povorcitinib. The 24-week data demonstrated deep and sustained improvements across key clinical endpoints, including HiSCR 50, 75, 90, and 100, resolution of draining tunnels, and effective reduction in flares. Povorcitinib also showed a rapid and robust reduction in skin pain, with 62% to 70% of patients reporting mild or no pain by week 24.

The 24 week data demonstrated deep and sustained improvement across key clinical endpoints, including high score 50, 70, 590, and 100 resolution of draining tunnels and effective reduction in flares.

Speaker #6: For the . Last month , we presented longer term data in Hydradenitis Suppurativa at the European Academy of Dermatology and Venereology Congress , which further reinforced the differentiated profile of NIB .

We're sitting they've also showed a rapid and robust reduction skin pain, 62% to 70% of patients reporting mild or no pain by week 24.

Speaker #6: The reporting of mild or no pain by week 24. Physicians experienced in the management of AJS emphasized that their primary focus when they treat patients with HS is on two elements: helping patients feel better by addressing the pain related to HS, and effectively controlling flares.

Precision is experiencing the management of a jazz emphasize as their primary focus when they treat patients with Hs is on two elements helped patients feel better by addressing the pain related to a jazz and to effectively control players. The data presented showed up over sitting it provides rapid and sustained pain relief and reduces the frequency of players.

This positive phase III results demonstrate the potential of polar sitting there to address the significant medical needs over the more than 300000 people living with moderate to severe hs offering and novel effective and convenient oral treatment option for this underserved patient population.

Pablo Cagnoni: Physicians experienced in the management of HS emphasize that their primary focus when they treat patients with HS is to help patients feel better by addressing the pain related to HS and to effectively control flares. The data presented show that povorcitinib provides rapid and sustained pain relief and reduces the frequency of flares. These positive Phase 3 results demonstrate the potential of povorcitinib to address the significant medical needs of the more than 300,000 people living with moderate to severe HS, offering a novel, effective, and convenient oral treatment option for this underserved patient population. Moving to slide 16 and the near-term opportunities for povorcitinib. As you know, HS is the most advanced program and we're on track with our regulatory submissions by the end of the year in the EU and early 2026 in the U.S., with potential approvals and launches in late 2026 and early 2027.

Speaker #6: The data presented showed that Sydney provides rapid and sustained pain relief and reduces the frequency of flares. These positive Phase 3 results demonstrate the potential of Power Sydney to address the significant medical needs of the more than 300,000 people living with moderate to severe HS, offering a novel, effective, and convenient oral treatment option for this underserved patient population.

Moving to slide 16 in the near term opportunities for power sitting there as you know Hs is our most advanced programs and we're on track with our regulatory submissions by the end of the year in the EU in early 2026 in the U S with potential approvals and launches in late 2026 early 'twenty 'twenty seven.

In addition to Hs or starting point, we're sitting here in three other indications underscoring its potential to become a major growth driver for the company.

Speaker #6: Moving to slide 16 and the near-term opportunities for power , Sydney . As you know , HS is the most advanced programs and worn track with a regulatory submissions .

Well, we're sitting there has been evaluated in phase III programs in vitiligo, and Perrigo inaugural Arris as well as a phase II proof of concept study in asthma.

Speaker #6: By the end of the year in the EU and early 2026 in the US, with potential approvals and launches in late 2026 and early 2027.

We anticipate pivotal data readouts for vitiligo in Pn in 2020 six with a goal of potential initial regulatory approvals in 2027 2028.

Speaker #6: In addition to HHS , we're studying positive in three other indications , underscoring its potential to become a major growth driver for the company over Sydney has been evaluated in phase three programs in vitiligo and prurigo , nodularis , as well as a phase two proof of concept study in asthma .

Pablo Cagnoni: In addition to HS, we're studying povorcitinib in three other indications, underscoring its potential to become a major growth driver for the company. Povorcitinib has been evaluated in Phase 3 programs in vitiligo and prurigo nodularis, as well as a Phase 2 proof-of-concept study in asthma. We anticipate pivotal data readouts for vitiligo and PN in 2026, with the goal of potential initial regulatory approvals in 2027 and 2028. Next, I would like to highlight two recent updates from our solid tumor portfolio, beginning with our TGFβR2 by PD-1 bispecific antibody program. This month at the European Society of Medical Oncology Annual Meeting, we presented initial Phase 1 data for INCB 033890, which I'll refer to moving forward. INCB 033890, our first-in-class TGFβR2 by PD-1 bispecific antibody, in patients with solid tumors. This is an Incyte discovered compound and one that is truly differentiated from other TGFβ and PD-1 approaches.

Next I would like to highlight two recent updates from our solid tumor portfolio, beginning with our TGF beta by PD, one by specific antibody program.

This month at the European Society of medical Oncology annual meeting, we presented initial phase one data for <unk>, CA 33890, which I'll refer to moving forward 890, our first in class TGF beta receptor two by PD, one by specific antibody in patients with solid tumors. This is.

Speaker #6: We anticipate pivotal data readouts for vitiligo and pain in 2026 , with the goal of potential initial regulatory approvals in 2027 . 2028 .

Speaker #6: Next , I would like to highlight two recent updates from our solid tumor portfolio , beginning with our TGF beta by PD one bispecific antibody program this month at the European Society of Medical Oncology Annual meeting .

And inside discovered compound and one that is truly differentiated from other TGF beta and PD one approaches.

Speaker #6: We presented initial phase one data for Inca 33890 . As I'll refer to moving forward , 890 . Our first in class TGF beta receptor two by PD one bispecific antibody .

The phase one trial evaluated <unk> in solid tumors with a focus on microsatellite stable or MSS colorectal cancer patients.

<unk> demonstrated durable single agent anti tumor activity and a manageable safety profile in heavily pretreated MSS colorectal cancer patients a population with limited treatment options and where anti PD. One PDL. One antibodies have historically produced response rates from zero to 2%.

Speaker #6: In patients with solid tumors , this is an inside discover compound and one that is truly differentiated from other TGF beta and PD one approaches the phase one trial evaluated 89 solid tumors with a focus on microsatellite stable or MSS colorectal cancer patients .

Pablo Cagnoni: The Phase 1 trial evaluated INCB 033890 in solid tumors with a focus on microsatellite stable, or MSS, colorectal cancer patients. INCB 033890 demonstrated durable single-agent antitumor activity and a manageable safety profile in heavily pretreated MSS colorectal cancer patients, a population with limited treatment options and where anti-PD-1/PD-L1 antibodies have historically produced response rates from 0 to 2%. In patients with MSS colorectal cancer, INCB 033890 achieved an overall response rate of 15%, and most notably, responses were observed in patients with and without liver metastasis. The majority of treatment-related adverse events were low grade, with no dose-limiting toxicities reported. We also completed a dose escalation of INCB 033890 in combinations of four cohorts: FOLFOX plus bevacizumab, FOLFIRI plus bevacizumab, bevacizumab, and cetuximab. No evidence of additive toxicity has been observed in any of the combination cohorts, and dose expansion is ongoing.

And patients with MSS colorectal 890 achieved an overall response rate of 15% and most notably responses were observed in patients with and without liver metastasis. The.

Speaker #6: 890 demonstrated durable single agent anti-tumor activity and a manageable safety profile in heavily pretreated MSS colorectal cancer patients . A population with limited treatment options and were anti-PD-1 , Pd-l1 antibodies have historically produced response rates from 0 to 2% in patients with MSS colorectal , 890 achieved an overall response rate of 15% , and most notably , responses were observed in patients with and without liver metastasis .

The majority of treatment related adverse events were low grade with no dose limiting toxicities reported.

We also completed the dose escalation of 890 in combinations or cohorts ballparks for our Bevacizumab fall theory, plus Bevacizumab bevacizumab as it tucks you map.

No evidence of additive toxicity has been observed in any of the combination cohorts and dose expansion is ongoing.

Speaker #6: The majority of treatment related adverse events were low grade , with no dose limiting toxicities reported . We have also completed a dose escalation of 890 in combinations of four cohorts folfox for bevacizumab , Folfiri plus bevacizumab , bevacizumab and cetuximab .

This initial results provide a strong rationale for advancing 890 into a registrational program.

We're planning to start a pivotal phase III trial evaluating <unk> in combination with standard of care chemotherapy and Bevacizumab in first line MSS colorectal cancer patients in 2026.

Speaker #6: No evidence of additive toxicity has been observed in any of the combination cohorts, and dose expansion is ongoing. These initial results provide a strong rationale for advancing 890 into the registrational program.

Turning to our <unk> program on slide 18.

Pablo Cagnoni: These initial results provide a strong rationale for advancing INCB 033890 into a registrational program. We're planning to start a pivotal Phase 3 trial evaluating INCB 033890 in combination with standard-of-care chemotherapy and bevacizumab in first-line MSS colorectal cancer patients in 2026. Turning to our KRASG12D program on Slide 18, we recently presented encouraging clinical data from the Phase 1 trial of INCB 161734, or as I'll refer to moving forward, 734, in heavily pretreated patients with advanced or metastatic solid tumors harboring the KRASG12D mutation, including pancreatic ductal adenocarcinoma among others. Results demonstrated a manageable safety profile with no dose-limiting toxicities observed and predominantly grade 1 treatment-related adverse events. Importantly, in pancreatic adenocarcinoma patients, 734 showed promising antitumor activity with an objective response rate of 34% and a disease control rate of 86% at the dose of 1200 mg.

Were recently presented encouraging clinical data from the phase one trial of <unk>, 161, 734, or our salaries start to moving forward 734 in heavily pretreated patients with advanced or metastatic solid tumors harboring the K rusty until the mutation, including pancreatic ductal adenocarcinoma among others.

Speaker #6: We're planning to start a pivotal Phase 3 trial evaluating 890 in combination with standard of care chemotherapy and bevacizumab in first-line MSS colorectal cancer patients in 2026.

Speaker #6: Turning to our Kras G12d program on slide 18 . We recently presented encouraging clinical data from the phase one trial of Incb 161734 .

Results demonstrated a manageable safety profile with no dose limiting toxicities observed and predominantly grade <unk> treatment related adverse events importantly in pancreatic adenocarcinoma patients 734 showed promising anti tumor activity with an objective response rate of 34% disease control rate of.

Speaker #6: Or , as I'll refer to , moving forward , 734 . In heavily pretreated patients with advanced or metastatic solid tumors harboring the Kras , g12d mutation , including pancreatic ductal adenocarcinoma , among others .

<unk>, 86% of the dose of 1200 milligrams.

Speaker #6: Results demonstrated a manageable safety profile with no dose limiting toxicities observed and predominantly grade one treatment related adverse events . Importantly , in pancreatic adenocarcinoma , patients , 734 showed promising anti-tumor activity with an objective response rate of 34% .

These results are particularly notable given that only eight of the patients were treated in the second line setting.

To summarize both our TGF beta by PD, one or a K rusty till deep programs represent significant opportunities to address large patient populations with high medical need specifically MSS colorectal cancer and pancreatic ductal adenocarcinoma.

Speaker #6: Disease control rate of 86% at the dose of 200mg . This results are particularly notable given that only eight of the patients were treated in the second line setting .

Pablo Cagnoni: These results are particularly notable given that only 8 of the patients were treated in the second-line setting. To summarize, both our TGFβR2 by PD-1 and our KRASG12D programs represent significant opportunities to address large patient populations with high medical need, specifically MSS colorectal cancer and pancreatic ductal adenocarcinoma. As Bill noted, our strategy in both cases would be to win in frontline in combination with standard of care. For 890, we have demonstrated durable single-agent activity in heavily pretreated MSS colorectal cancer patients, including those with liver metastasis, and a favorable safety profile and combinability for first-line standard care regimens. As previously mentioned, we're planning to initiate a phase 3 study in first-line MSS colorectal in 2026. Similarly, 734 has shown promising antitumor activity and manageable safety profile in advanced solid tumors, with particularly encouraging results in PDAC. We'll share more updates on this program next year.

Notice our strategy in both geysers will be to win in frontline in combination with standard of care.

Speaker #6: To summarize , both our TGF beta by PD one and our Kras g12d programs represent significant opportunities to address large patient populations with high medical need .

<unk> zero, we have demonstrated durable single agent activity in heavily pretreated, MSS colorectal cancer patients, including those with liver metastases and a favorable safety profile and combinability with first line standard of care regimens.

Speaker #6: Specifically , MSS , colorectal cancer , and pancreatic ductal adenocarcinoma . As Bill noted , our strategy in both cancers will be to win in front line in combination with standard of care 49 zero .

Betsy mentioned, we're planning to initiate a phase III study in first line MSS colorectal until May 26.

Similarly, 734 has shown promising on tech tour activity and manageable safety profile and advanced solid tumors with particularly encouraging results and feedback we will share more updates on this program next year.

Speaker #6: We have demonstrated durable single agent activity in heavily pretreated MSS colorectal cancer patients , including those with liver metastases and a favorable safety profile and combinability with first line standard of care regimens .

Now to slide 20.

Speaker #6: As previously mentioned , we're planning to initiate a phase three study in first line MSS colorectal in 2026 . Similarly , 734 has shown promising anti-tumor activity and manageable safety profile in advanced solid tumors with particularly encouraging results in pdac .

225 has been a pivotal year for our inside highlighted by multiple new product launches pivotal trial, Readouts and phase III study initiations and proof of concept results.

These accomplishments reflect the solid progress we've made so far towards the milestones we established at the beginning of the year.

Speaker #6: We'll share more updates on this program next year . Now to slide 20 , 2025 has been a pivotal year for Incyte , highlighted by multiple new product launches , pivotal trial readouts , phase three study initiations , and proof of concept results .

As we look at the remainder of the year, we plan to share data for the first time on 99 are mutant.

Pablo Cagnoni: Now to slide 20. 2025 has been a pivotal year for Incyte, highlighted by multiple new product launches, pivotal trial readouts, phase 3 study initiations, and proof-of-concept results. These accomplishments reflect the solid progress we've made so far toward the milestones we established at the beginning of the year. As we look at the remainder of the year, we plan to share data for the first time on 9A9, our mutant CALR antibody in patients with myelofibrosis. We are evaluating 989 in a broad population of patients with MF. There are three actively enrolling cohorts. First, intermediate to high-risk patients who are intolerant, ineligible, or resistant to a JAK inhibitor. This cohort is evaluating 9A9 as a monotherapy. Second, intermediate to high-risk patients who are on ruxolitinib but experience a suboptimal spleen response after at least 12 weeks of treatment. In this cohort, we are evaluating adding 9A9 to ruxolitinib.

Our antibody in patients with myelofibrosis.

We are evaluating 99 or a broad population of patients with MF. There are three actively enrolling cohorts first intermediate to high risk patients, who are intolerant ineligible or resistant to a JAK inhibitor. This cohort is evaluating 99 as a monotherapy.

Speaker #6: This accomplishment reflects the solid progress we've made so far toward the milestones we established at the beginning of the year. As we look at the remainder of the year, we plan to share data for the first time on nine, eight, nine.

Speaker #6: Our mutant color antibody . In patients with myelofibrosis , we are evaluating 99 . In a broad population of patients with MF , there are three actively enrolling cohorts first , intermediate to high risk patients who are intolerant , ineligible or resistant to a Jak inhibitor .

Second intermediate to high risk patients, who are on <unk>, but experienced a sub optimal spleen response after at least 12 weeks of treatment in this cohort we are evaluating adding 99 to Russell isn't it.

And finally, we're enrolling patients with intermediate to high risk treatment nave MF in a cohort evaluating 99 compared to a combination of $99. <unk>. This will allow us to see how 90 nonperformance as a monotherapy and in combination with rux loopnet and treatment naive patients.

Speaker #6: This cohort is evaluating nine nine as a monotherapy . Second , intermediate to high risk patients who are on Ruxolitinib but experienced a suboptimal spleen response after at least 12 weeks of treatment .

Speaker #6: In this cohort , we are evaluating adding nine nine to Ruxolitinib . And finally , we're enrolling patients with intermediate to high risk treatment naive MF in a cohort evaluating 989 compared to a combination of nine nine and ruxolitinib .

Our update later this year will include early data from the first two cohorts.

Pablo Cagnoni: Finally, we're enrolling patients with intermediate to high-risk treatment-naive MF in a cohort evaluating 9A9 compared to a combination of 989 and ruxolitinib. This will allow us to see how 9A9 performs as a monotherapy and in combination with ruxolitinib in treatment-naive patients. Our update later this year will include early data from the first two cohorts. For the monotherapy cohort, we plan to share data from roughly 50 patients. Approximately two-thirds of them will have more than 24 weeks of follow-up. Additionally, data will be presented for the combination cohort in at least 15 suboptimal respondents to ruxolitinib. More than half of these patients will have a minimum of 24 weeks of follow-up.

So the monotherapy cohort, we plan to share data from roughly 50 patients.

<unk> two thirds of them will have more than 24 weeks of follow up.

Speaker #6: This will allow us to see how 99 performs as a monotherapy and in combination with in treatment , naive patients . Our update later this year will include early data from the first two cohorts for the monotherapy cohort .

<unk> data will be presented for the combination cohort and at least 15 suboptimal responders to rux splitting it more than half of these patients will have a minimum of 24 weeks of follow up.

Partly the update will include response data using traditional endpoints as we at 25, <unk> 35, TSS 50, and anemia and molecular endpoints like effects on the Vas in whole blood CD 34 positive mutant call ourselves in peripheral blood mononuclear cells.

Speaker #6: We plan to share data from roughly 50 patients , approximately two thirds of them will have more than 24 weeks of follow up .

Speaker #6: Additionally , data will be presented for the combination cohort and at least 15 suboptimal responders to ruxolitinib more than half of these patients will have a minimum of 24 weeks of follow up .

And call it positive Mega carrier sites in the bone marrow.

Speaker #6: Importantly , the update will include response data used in traditional endpoints SVR 25 , SVR 35 , TSS 50 , and anemia , and molecular endpoints like effects on Vaf in whole blood .

Additionally, we'll provide an update on 99 treated patients with essential thrombocythemia as a follow up to the encouraging results per center earlier this year.

Pablo Cagnoni: Importantly, the update will include response data used in traditional endpoints SVR 25, SBR 35, TSS 50, and anemia and molecular endpoints like effects on VAF in whole blood, CD34 positive mutant CALR cells in peripheral blood, mononuclear cells, and mutant CALR positive megakaryocytes in the bone marrow. Additionally, we'll provide an update on 989 treated patients with essential thrombocythemia as a follow up to the encouraging results presented earlier this year. As you'll recall from the EHA presentation, 989 demonstrated the rapid and sustained normalization of platelet counts and was well tolerated with only one patient discontinuing due to an adverse event. We look forward to sharing updates on the remaining 2025 milestones and to provide further visibility into our 2026 catalyst as we continue to advance our pipeline. With that, I'll turn it over to Tom for a financial update on the quarter. Thanks, Pablo.

You will recall from DHA presentation, 99 demonstrated a rapid and sustained normalization of platelet counts and was well tolerated with only one patient discontinued due to an adverse event.

Speaker #6: Cd34 positive mutant color cells in peripheral blood mononuclear cells and mutant color positive megakaryocytes in the bone marrow . Additionally , we'll provide an update on 99 treated patients with essential ruxolitinib thrombocythaemia as a follow up to the encouraging results presented earlier this year .

We look forward to sharing updates on our remaining 2025 milestones and to provide further visibility into our 2026 catalysts as we continue to advance our pipeline.

Speaker #6: As you'll recall from presentation , 99 demonstrated the rapid and sustained normalization of platelet counts and was well tolerated , with only one patient discontinued due to an adverse event .

That I will turn it over to Tom for financial update on the quarter. Thanks, Pablo as Phil mentioned earlier, our total revenues and product revenues were $1 37 billion and 1.15 billion respectfully, increasing 20% and 19% from the prior year.

Speaker #6: We look forward to sharing updates on the remaining 2025 milestones and to provide further visibility into our 2026 catalyst as we continue to advance our pipeline.

Our total GAAP R&D expenses were $507 million in the third quarter, excluding one time expenses in the prior year R&D expenses increased 7% year over year, driven by continued investment in our late stage development assets moving to SG&A total GAAP SG&A expenses were $329 million in the third quarter, increasing 6%.

Speaker #6: With that, I'll turn it over to Tom for a financial update on the quarter.

Speaker #7: Thanks , Pablo . As Bill mentioned earlier , our total revenues and product revenues were 1.3 7,000,000,001.15 billion , respectively , increasing 20% and 19% from the prior year .

Pablo Cagnoni: As Bill mentioned earlier, our total revenues and product revenues were $1.37 billion and $1.15 billion, respectively, increasing 20% and 19% from the prior year. Our total GAAP R&D expenses were $507 million in the third quarter, excluding one-time expenses in the prior year. R&D expenses increased 7% year over year driven by continued investment in our late-stage development assets. Moving to SG&A, total GAAP SG&A expenses were $329 million in the third quarter, increasing 6% year over year, primarily driven by international marketing activities to support product launches. Ongoing operating expenses in the third quarter increased 8% year over year compared to an 18% increase in ongoing revenues during the same period, leading to a continued increase in operating leverage and margins. Based on the growth of our product portfolio, we raised 2025 full year net product revenue guidance to $4.23 to $4.32 billion.

<unk> year over year, primarily driven by international marketing activities to support product launches.

Speaker #7: Our total GAAP R&D expenses were 507 million in the third quarter , excluding one time expenses in the prior year , R&D expenses increased 7% year over year , driven by continued investment in our late stage development assets .

Ongoing operating expenses in the third quarter increased 8% year over year compared to a 18% increase in ongoing revenues during the same period, leading to a continued increase in operating leverage and margins.

Speaker #7: Moving to SG&A , total gap SG&A expenses were 329 million in the third quarter , increasing 6% year over year , primarily driven by international marketing activities to support product launches , ongoing operating expenses in the third quarter increased 8% year over year compared to a 18% increase in ongoing revenues during the same period , leading to a continued increase in operating leverage and margins based on the growth of our product portfolio , we raised 2025 full year net product revenue guidance to 4.23 to 4.32 billion .

Just on the growth of our product portfolio. We raised 2025 full year net product revenue guidance for two three to 432 billion. We maintained our prior opex guidance of $3 two five to $3 31 billion, which reflects combined R&D and SG&A GAAP expenses I'll now turn the call over to Bill.

Right.

Thanks, Tom that concludes our prepared remarks, please open the line for Q&A.

Certainly, we'll now be conducting a question and answer session if you'd like to be placed in the question queue. Please press star one on your telephone keypad.

Speaker #7: We maintain our prior OpEx guidance of 3.25 to 3.31 billion , which reflects combined R&D and SG&A gap expenses . Now , I'll turn the call over to Bill .

Pablo Cagnoni: We maintain our prior OpEx guidance of $3.25 to $3.31 billion, which reflects combined R&D and SG&A GAAP expenses. I'll now turn the call over to Bill.

Formation tone will indicate your line is in the question queue. You May press star two if he would like to move or question from the queue and as a reminder, we ask you. Please ask one question one follow up then return to the queue.

Speaker #5: Thanks , Tom . That concludes our prepared remarks . Please open the line for Q&A .

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

First question today is coming from from Bank of America. Your line is that right.

Speaker #2: Certainly, we will not be conducting a question-and-answer session. If you'd like to be placed into the question queue, please press star one on your telephone keypad.

Alexis Smith: Certainly. We'll now be conducting a question and answer session. If you'd like to be placed into the question queue, please press star 1 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, one follow-up, then return to the queue. Our first question today is coming from Fazee Ahmed from Bank of America. Your line is now live.

Hey, guys. Good morning, Thanks for taking my question I wanted to focus on that.

Speaker #2: A confirmation tone will indicate your line is in the question queue . You may press star two if you'd like to move your question from the queue .

Coming <unk>.

And do you have enough.

How many patients worth of data to make back. They did most people are going to be focus on the monotherapy arm, how important is that going to be.

Speaker #2: And as a reminder , we ask that you please ask one question , one follow up , then return to the queue . Our first question today is coming from Tazeen Ahmad from Bank of America .

For people to believe that you have kind of been efficacy as a standalone because there could potentially be the view that you know it could be synergistic with when added to jakafi. So can you maybe level set for us what level of efficacy you are going to think it's going to be convincing enough to move it forward, even if it's any.

Speaker #2: Your line is now live .

Speaker #8: Hi guys . Good morning . Thanks for taking my question . I wanted to the upcoming McKellar data . You've given us a good preview of how many patients worth of data to expect .

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

Speaker #8: I think most people are going to be focused on the monotherapy arm . How important is that going to be for for people to believe that you have convinced efficacy as a stand alone , because there could potentially be the view that it could be synergistic with when added to .

Combination with Jakafi.

Thanks to <unk> ill turn it over to Pablo.

Thank you for the question so.

I think it's important to remember a couple of things about them you can call. Our antibody program. The first is this is the very first targeted therapy for patients with Mpls and we're talking about MF, but broadly speaking for myeloproliferative neoplasms, both MF and 18. This case does that first drove your targeted therapy as opposed to nonspecific therapies in the past.

Speaker #8: Jakafi . So can you maybe level set for us what level of efficacy you're going to think is going to be convincing enough to move it forward , even if it's focus on combination with Jakafi ?

Speaker #8: Thanks .

Speaker #5: Thanks, Tazeen. I'll turn it over to Pablo.

Hervé Hoppenot: Thanks, Tazeen. I'll turn it over to Pablo.

Speaker #6: Thank you for the question . So I think it's important to remember a couple of things about our mutant antibody program . The first is this is the very first targeted therapy for patients with Mpns .

Pablo Cagnoni: Thank you for the question. I think it's important to remember a couple of things about our mutant CALR antibody program. The first is this is the very first targeted therapy for patients with MPNs, and we're talking about MF, but broadly speaking for myeloproliferative neoplasms, both MF and ET. In this case, this is the first truly targeted therapy as opposed to nonspecific therapies in the past, including ruxolitinib, that were mostly symptomatic improvements with very little effect on disease modification. You're asking specifically about the updated ASH. I think it's very important for us to demonstrate that there is single agent activity with 989. That's why the update will include a large number of patients, as I mentioned, 50 patients with somewhat significant follow up to really prove convincingly that 989 has single agent activity.

Including a rock slipped in there that were mostly symptomatic improvement with very little.

Effect on disease modification now youre, asking specifically about the update at Ash I think it's very important for us to demonstrate that there is single agent activity with 99, that's why.

Speaker #6: And we're talking about MF , but broadly speaking , for peripheral neoplasms , both MF and in this case this is the first truly targeted therapy as opposed to nonspecific therapies in the past , including ruxolitinib that were mostly symptomatic improvements with very little effect on disease modification .

The update will include a large number of patients as I mentioned 50 patients with somewhat significant follow up to really.

Roof convincingly that 99 has single agent activity the focus will be adjusted on clinical endpoints, which we believe are critical spleen reduction symptom improvement anemia, but also has settled translational endpoints, which we think are really important to confirm our view that this new medication has potential disease <unk>.

Speaker #6: Now you're asking specifically about the updated Ash . I think it's very important for us to demonstrate that there is single agent activity with 99 .

Speaker #6: That's why the update will include a large number of patients . As I mentioned , 50 patients with somewhat significant follow up to really prove convincingly that 99 has single agent activity .

Define effect so it does our benchmarks around efficacy in previously treated patients with JAK inhibitors, I think the best benchmark, we have recently used monologue nib.

Speaker #6: The focus will be not just on clinical endpoints , which we believe are critical . Spleen reduction symptom improvement , anemia , but also a set of translational endpoints which we think are really important to confirm our view that this new medication has potential disease modifying effects .

Pablo Cagnoni: The focus will be not just on clinical endpoints, which we believe are critical—spleen reduction, symptom improvement, anemia—but also a set of translational endpoints, which we think are really important to confirm our view that this new medication has potential disease modifying effects. In terms of benchmarks around efficacy in previously treated patients with JAK inhibitors, I think the best benchmark we have recently is momelatinib. As you know, momelatinib has an SVR 35 of between 7% and 22% in different studies, with the TSS 50 improvements in the 25% to 26%. Those are some reasonable benchmarks in the second line setting to look at. It's very important for us to confirm the single agent activity of 989 in MF patients.

As you know I'm I'm allowed nave has an SVR thirty-five are between seven and 22% in different studies.

With the TSS 50 improvements in the 25% to 26%.

Those are some reasonable benchmarks in the second line setting to look at but it is very important for us to confirm the single agent activity of 909 in MF patients doesn't.

Speaker #6: So in terms of benchmarks around efficacy in previously treated patients with Jak inhibitors , I think the best benchmark we have recently is momelotinib .

Speaker #6: As you know, Momelotinib has an SVR 35 of between 7% and 22% in different studies, with the SSE 50 improvements in the 25% to 26% range.

Thanks for the question.

Okay.

Thank you next question today is coming from Andrew Berens from Leerink Partners. Your line is now live.

Hi, Thanks, and congratulations on the execution during the quarter.

Speaker #6: Those are some reasonable benchmarks . In the second line setting to look at , but it's very important for us to confirm the single agent activity of 99 in MF patients , as in .

I was wondering if you could give us some more color on the decision to terminate the Volvo program issue.

Following our announcement in April.

Speaker #5: Thanks for the question .

Hervé Hoppenot: Thanks for the question.

It is true successful.

Are we going to see the data at a medical meeting as you previously guided.

Speaker #2: Thank the next question . Today is coming from Andrew Barnes from Learning Partners . Your line is now live .

Alexis Smith: Thank you. The next question today is coming from Andrew Berens from Leerink Partners. Your line is now live.

Yeah, Andy I'll start off and then turn it over to Pablo as it relates to Pogo for CSU. It came down for us the priorities.

Speaker #9: Hi . Thanks . And congratulations on the execution . During the quarter , I was wondering if you could give some more color on the decision to terminate the program and CSU , following your announcement in April .

Pablo Cagnoni: Hi. Thanks, and congratulations on the execution during the quarter. I was wondering if you can give some more color on the decision to terminate the FOVO program in CSU following your announcement in April that it was phase two successful. Are we going to see the data at a medical meeting as you previously guided?

We have to win we are prioritizing projects with better returns profile. It was a good phase II program, but we have better phase III programs and the factors that went into the decision included differentiation competitive intensity timing to market and market market potential among other factors and Pablo you want to just comment on the <unk>.

Speaker #9: That was a phase two is successful . Are we going to see the data at a medical meeting as you previously guided ?

Speaker #5: Yeah . Andy , I'll start off and then turn it over to to Pablo as it relates to parvo for CSU . It came down for us to prioritize .

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

<unk> of the data.

Speaker #5: We have to when we are prioritizing projects with better returns , profile . It was a good phase two program , but we have better phase three programs .

Certainly we are we haven't decided with investigators whether to release the data, but I will almost certainly do that at some future conference Andy the one other point out without to Bill's point is that in addition to those factors the regulatory bar in CSU, we discussed with FDA and their requirements for potential.

Speaker #5: And the factors that went into the decision included differentiation , competitive intensity , timing to market and market , market potential , among other factors .

Speaker #5: And Pablo , you want to just comment on the release of the data ?

The pivotal program in CSU, we're pretty onerous and we decided we had a lot of progress to focus on.

Speaker #6: Certainly we are we haven't decided with investigators whether to release the data , but we'll almost certainly do that at some future conference .

Pablo Cagnoni: Certainly. We haven't decided with investigators whether to release the data, but we'll almost certainly do that at some future conference. Andy, the one other point I would add to Bill's points is that in addition to those factors, the regulatory bar in CSU we discussed with FDA and the requirements for potential pivotal program in CSU were pretty onerous, and we decided we had other priorities to focus on. Okay, thanks. If I could, just a question on the PB1 PGF beta. I was at ESNO. I thought it was really encouraging. You guys are advancing into phase three. Are we going to see combination data before you make that decision to advance? Is there, like, I think there's a run-in, looks like, on the clinicaltrials.gov, so the decision to advance the TGFβR2 by PD-1 program in combination with chemotherapy first-line colorectal is made.

Okay. Thanks, and then if I could just a question on the PD one.

Speaker #6: Andy , the one other point I would add to to Bill's points is that in addition to those factors , the regulatory bar and CSU , we discussed with FDA and the requirements for potential pivotal program in CSU were pretty onerous .

How is that has no I thought it was really encouraging and you guys are advancing in a phase three or are we going to see combination data before you make that decision to advances there like I think there's like a run in looks like on the clinical trials Gov.

Speaker #6: And we decided we had other priorities to focus on.

So the decision to advance the TGF beta receptor two by PD one program in combination with chemotherapy in first line called Iraq, others made we're moving forward in that direction in parallel with that we're generating data with the combination and we will release that data at some point next year, Andy but.

Speaker #9: Okay . Thanks . And then if I could just a question on the Pb1 TGF beta , I was at and I thought it was really encouraging .

Speaker #9: And you guys are advancing into phase three , are we going to see combination data before you make that decision to advance ? Is there like I think there's like a run in looks like on the clinical Trials.gov .

Those two things are happening in parallel we think speed is of the essence here and executing this phase III trial. So we're advancing this rapidly and will generate the data and release that at some point.

Speaker #6: So the decision to advance the TGF beta receptor two by PD one program in combination with chemotherapy in first line colorectal is made .

Speaker #6: We're moving forward in that direction in parallel with that . We're generating data with the combination . And we will release that data at some point next year .

Pablo Cagnoni: We're moving forward in that direction. In parallel with that, we're generating data with the combination, and we will release that data at some point next year. Andy, those two things are happening in parallel. We think speed is of the essence here in executing this phase three trial. We're advancing this rapidly, and we'll generate the data and release it at some point.

Thank you. Your next question today is coming from Stephen Willey from Stifel. Your line is now live.

Yeah. Good morning, just two quick ones for me so on on.

Speaker #6: And the but those two things are happening in parallel . We think speed is of the essence here . And executing this phase three trial .

On 99 was just wondering if you could give a little bit of color around what we should expect to see within the abstract publication next week just relative to the presentation itself.

Speaker #6: So we're advancing this rapidly, and we'll generate the data and release it at some point.

And then just a quick one on the timber curious how you're thinking about San if he's failed frontline trial with a reservoir rock steroids in terms of.

Speaker #2: Thank you . Next question today is coming from Stephen Woolley from Stiefel . Your line is now live .

Alexis Smith: Thank you. Next question today is coming from Steven Willey from Stifel. Your line is now live.

Speaker #10: Yeah . Good morning . Just two quick ones for me . So on on 99 was just wondering if you could give a little bit of color around what we should expect to see within the abstract publication next week ?

Hervé Hoppenot: Yeah, good morning. Just two quick ones for me. On 989, was just wondering if you could give a little bit of color around what we should expect to see within the abstract publication next week just relative to the presentation itself, and then just a quick one on Naktimvo. Curious how you're thinking about Sanofi's failed frontline trial with Resarox steroids in terms of read through to the ongoing phase three trial with Naktimvo and just whether you think that might say anything about the biology of the disease being different in a newly diagnosed patient. Thanks. Yeah, thanks. Thanks for the question, Steve. I'm going to turn the second question about Naktimvo over to Steven Stein, and then Pablo will grab the first question.

In terms of read through to the ongoing phase III trial with the timber and just whether you think that might say anything about the biology of the disease being different in the newly diagnosed patients.

Speaker #10: Just relative to the presentation itself . And then just a quick one on curious how you're thinking about Sanofi's failed front line trial with steroids in terms of in terms of read through to the ongoing phase three trial with Nick Timbo ?

Yeah. Thanks, Thanks for the question, Steve I'm going to turn the second question about Nick timber over to Steven Stein and then Pablo grab the first question yes.

Yeah, Steve Thanks for the question in terms of first line graph versus host disease in combination with steroids Israeli.

Speaker #10: And just whether you think that might say anything about the biology of the disease being different in a newly diagnosed patient . Thanks .

A little bit of controversy around how you measure the primary endpoint and event free survival and there is some nuances there on what you call event. So we think our definition.

Speaker #5: Yeah , thanks . Thanks for the question , Steve . I'm going to turn the second question about Nick . Timbo over to Stephen Stein and then Pablo will grab the first question .

Is robust and is powered to adequately show the difference we need to beat steroids and as Bill said in his prepared remarks to also show something doctors very much desire steroid withdrawal as rapidly as possible to avoid side effects, but you're right in the sense that it's you know it shows the defeat.

Speaker #11: Yeah . Steve , thanks for the question . In terms of first line graph versus host disease in combination with steroids , there's really a little bit of controversy around how you measure the primary endpoint and event free survival .

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

Speaker #11: And there's some nuances there on what you call events . So we think our definition is robust and is powered to adequately show the difference .

Multi in this arena of Eaton steroids, which are active but we really think it's around the definition of the endpoint and we our endpoint is robust and meets the needs for our program and we're confident about it.

Speaker #11: We need to beat steroids . And as Bill said in his prepared remarks to also show something doctors very much desire steroid withdrawal as rapidly as possible to avert side effects .

Steve the only other thing I would add Steve here as we Fortunately with Nick timber have two shots on goal. We have a combination study with with steroids and with Jakafi. Obviously these are calculated risks you get a combination study with Jakafi, that's positive and youre going to two X. The addressable population and then you have a steroid free regimen.

Speaker #11: But you're right in the sense that it's you know , it shows the difficulty in the arena of beating steroids , which are active .

Speaker #11: But we really think it's around the definition of the endpoint . And we our endpoint is robust and meets the needs for our program .

Speaker #11: And we're confident about it . Thanks .

Obviously, you want both these programs to work one of to work it could change the trajectory of Nick timber fairly significantly.

Speaker #5: Thanks , Stephen . The only other thing I would add , Steve here is we fortunately with Nick , Timbo have two shots on goal .

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

Speaker #5: We have the combination study with with steroids and with Jakafi . Obviously these are calculated risks . You get a combination study with Jakafi .

I wont address the first question.

Certainly with 99.

I think it's important to focus on the presentation. We will have before the end of the year. That's a later data cut it's going to have more patients just kind of have longer follow up.

Speaker #5: That's positive and you're going to two x the addressable population . And then you have a steroid free regimen . Obviously you want both these programs to work .

I realize that the abstracts will be released but I would ask you to wait for the update will provide before the end of the year and focus on that because its more substantial and in particular, a follow up is substantially longer.

Speaker #5: One of two work . It could change the trajectory of Nick Timbo fairly significantly . Pablo , you want to address the first question ?

Speaker #6: Certainly with nine , eight , nine , I think it's important to focus on the presentation . We'll have before the end of the year .

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

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

Speaker #6: That's a later data cut . It's going to have more patients . It's going to have longer follow up . So I realize that the abstracts released .

Oh, Hey, guys congrats on the quarter and thanks for taking the questions can you describe the rationale behind terminating the bet inhibitor program was that mostly related to your strategic focus on targeted therapies like in Cal are in myelofibrosis.

Speaker #6: But I would ask you to wait for the update. We'll provide it before the end of the year. And focus on that, because it's more substantial and particularly follow-up is substantially longer.

Speaker #2: Thank you . The next question today is coming from Jay Olsen from Oppenheimer . Your line is now live .

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

And as a follow up to that question since the bet inhibitor was on track to begin Registrational studies, how soon can you move and Cal or into Registrational studies. Thank you.

Speaker #12: Oh , hey , guys , congrats on the quarter and thanks for taking the questions . Can you describe the rationale behind terminating the Bet inhibitor program ?

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

Jay Thanks for the questions I'll take the first part and then turn it over to to Pablo as it relates to the bet inhibitor the risk benefit calculus as you know for bet inhibitors right now is complex differentiating.

Speaker #12: Was that mostly related to your strategic focus on targeted therapies like McKellar and myelofibrosis ? And as a follow up to that question , since the Bet inhibitor was on track to begin registrational studies , how soon can you move McKellar into registrational studies ?

Class wide risks from molecule specific ones is challenging and so in general we're prioritizing programs with a higher P. Trs and a clearer path to market and that was fundamentally why we stopped the bet inhibitor program and then I'll, let Pablo comment further.

Speaker #12: Thank you .

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

Speaker #5: Jay , thanks for the questions . I'll take the first part and then turn it over to to to Pablo as it relates to the Bet inhibitor .

Speaker #5: The risk benefit calculus , as you know , for Bet inhibitors right now is complex . Differentiating class wide risks from molecule specific ones is challenging .

So.

I don't have anything to add in terms of the reasons for terminated that program in terms of the call. Our antibody program. Jay the goal is to start one or more pivotal trials in 2026, as we mentioned during our update any T.

Speaker #5: And so in general , we're prioritizing programs with a higher Tas and a clearer path to market . And that was fundamentally why we stopped the the Bet inhibitor program .

Speaker #5: And then I'll let Pablo comment further .

<unk> will likely be the first pivotal trial to start and that should start at some point in the first half of the year.

Speaker #6: So I don't have anything to add in terms of the reasons for terminating that program in terms of the color antibody program . Jay , the goal is to start one or more pivotal trials in 2026 .

Pablo Cagnoni: I don't have anything to add in terms of the reasons for terminating that program in terms of the CALR antibody program. Jay, the goal is to start one or more pivotal trials in 2026. As we mentioned during our EHA update in ET, ET will likely be the first pivotal trial we start, and that should start at some point in the first half of the year. In parallel with that, we are having regulatory interactions and continue to review the data in order to decide the right trials and the timing for implementing phase 3 trials for patients with myelofibrosis that most likely start at some point in the second half of 2026. I think that one thing that I would like to emphasize is the termination of the BET program in no way reduces our ambition in MPNs.

In parallel with that we are having regulatory interactions and continue to do.

We view the data in order to decide the right trials and the timing for implementing phase III trials for patients with myelofibrosis that most likely start at some point in the second half of 2026, I think that one thing that I would like to emphasize is the termination of the bed program in no way reduces our ambition and mpls as I mentioned earlier.

Speaker #6: As we mentioned during our update in ETI , ET will likely be the first pivotal trial we start . And that should start at some point in the first half of the year .

Speaker #6: In parallel with that , we are having regular interactions and continue to review the data in order to decide the right trials and the timing for implementing phase three trials for patients with myelofibrosis that most likely start at some point in the second half of 2026 .

This year our goal by the end of the decade is to have a solution for every single patient with a myeloproliferative neoplasm. We're building a pipeline of targeted therapies to address that need and we intend to continue to advance those programs.

Speaker #6: I think that one thing that I would like to emphasize is the terminus of the Bet program in no way reduces our ambition in Mpns , as I mentioned earlier this year , our goal by the end of the decade is to have a solution for every single patient with a myeloproliferative neoplasm .

Thanks Jack.

Thank you. Your next question today is coming from gene <unk> from Deutsche Bank. Your line is now live.

Good morning. Thank you for the question first of all as for Pablo Pablo Appreciate 99, as a targeted therapy for MTS, but can you say, whether or not we should expect SCR TSS and anemia burden at least on the kinetics fun to look similar to rocks and follow up for Bill Jackson seat comfort wanted to set a high bar for fall.

Pablo Cagnoni: As I mentioned earlier this year, our goal by the end of the decade is to have a solution for every single patient with a myeloproliferative neoplasm. We're building a pipeline of targeted therapies to address that need, and we intend to continue to advance those programs.

Speaker #6: We're building a pipeline of targeted therapies to address that need , and we intend to continue to advance those programs .

Speaker #5: Thanks , Jack .

Hervé Hoppenot: Thanks, Jack. Thank you.

Speaker #2: Thank you . Next question today is coming from James Shin from Deutsche Bank . Your line is now live .

Alexis Smith: Next question today is coming from James Shin from Deutsche Bank. Mine is now live.

Myelofibrosis, so from a timing financial and regulatory perspective can you share insights progress on gaining certainty for 99 Chipotle ethanol in the past and will that develop pass align with jakafi.

Speaker #13: Good morning . Thank you for the question . First one is for Pablo . Pablo , appreciate 989 is a targeted therapy for mpns .

Hervé Hoppenot: Good morning.

Pablo Cagnoni: Thank you for the question. First one is for Pablo. Pablo, appreciate 989 as a targeted therapy for MPNs, but can you say whether.

Speaker #13: But can you say whether or not we should expect SVR , TS and anemia burden , at least on the kinetics front , to look similar to Rux and follow up for Bill , Jack and comfort one and two set a high bar for front line myelofibrosis .

Hervé Hoppenot: or not we should expect serum TSS and anemia burden, at least on the kinetics front, to look similar to ruxolitinib and follow up for Bill, Jakafi's COMFORT.

Thank you.

Yeah, Alright, Pablo you can take the first part of the question.

So thank you for the question.

Pablo Cagnoni: One and two set a high bar for frontline myelofibrosis.

Speaker #13: So from a timing , financial and regulatory perspective , can you share insights progress on gaining certainty for 989 ? Front line MF development path and and will that development path align with Jack Kofi's Lowe ?

It is very important for us to address your question directly is very important for us to demonstrate that 99 has an effect on clinical endpoints in myelofibrosis. That's why the presentation will include as we are twenty-five SVR thirty-five TSS 50 effect and effects and anemia, we'll realize those are.

Hervé Hoppenot: From a timing, financial, and regulatory perspective, can you share insights and progress on gaining certainty for 989's frontline MPN development path, and will that development path align with Jakafi's LOE? Thank you. All right, Pablo, you can take the first part of the question.

Speaker #13: Thank you .

Speaker #5: Yeah . All right Pablo you can take the first part of the question .

Speaker #6: So thank you for the question . It is very important for us to address your question directly . It's very important for us to demonstrate that 989 has an effect on clinical endpoints in myelofibrosis .

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

Combination of those are the approvable endpoints in MF and showing efficacy in those same points is critical for this program. So those will be part of the update we provided before the end of the year, Let me pass it back to Bill Yeah, and as it relates to both 989 in E T and MF and how we think about the business post 2029.

Speaker #6: That's why the presentation will include SVR 25 , SVR 35 , SX 50 effect and effects in anemia . We realize those are a combination of those are the approval endpoints in MF and showing efficacy in those samples is critical for this program .

Filling a revenue gap is not one 989 does with 989 does is build a long duration.

Speaker #6: So, those will be part of the update we provide before the end of the year. Let me pass it back to Bill.

Revenue and cash flow stream well into the next decade. So we don't see the end of the road and Here's how you think about second line first line.

Speaker #5: Yeah . And as it relates to both 989 and ET and MF and how we think about the business , post 2029 , you know , filling a revenue gap is not , what , 989 does .

Hervé Hoppenot: As it relates to both 989 and Naktimvo and how we think about the business post-2029, filling a revenue gap is not what 989 does. What 989 does is build a long duration revenue and cash flow stream well into the next decade. We do not see the end of the road. Here is how I think about second line, first line. Pablo commented on this. There are targeted treatments available in many other cancers. That is not true in MPNs. For hematologists, there is intrinsic appeal to the first targeted therapy. When you take a look at ET, hydroxyurea is the standard of care. It is the most widely used cytoreductive agent in ET, but it achieves only a partial response, not a complete response in most patients. There are three consequences to that.

And Pablo commented on this there are targeted.

Treatments available in many other cancers that is not true in mpls and so for Hematologists. There is intrinsic appeal to the first targeted therapy.

Speaker #5: What 989 does is build a long duration revenue and cash flow stream well into the next decade . So we don't see the the end of the road .

And when you take a look at ETE Hydroxyurea is the standard of care is the most widely used side, a reductive agents E T. But it achieves only a partial response not a complete response in most patients and theres three consequences to that the first one is residual symptoms not as significant as it is in MF, but residual symptoms. The second consequence.

Speaker #5: And here's how I think about second line . First line . And Pablo commented on this . There are targeted treatments available in many other cancers .

Speaker #5: That is not true in Mpns . And so for hematologists there is intrinsic appeal to the first targeted therapy . And when you take a look at ET , hydroxyurea is a standard of care .

If residual thrombotic risk and the third consequence is residual.

Speaker #5: It's the most widely used cytoreductive agent in ET, but it achieves only a partial response, not a complete response, in most patients.

Transformational risk.

989 solves the problems at H, you created and even in a second line single agent study or with those data I expect at 99 will reshape the use of Hydroxyurea, where patients transition off of therapy rapidly because 989 is targeting disease, causing cells.

Speaker #5: And there's three consequences to that . The first one is residual symptoms , not as significant as it is in MF , but residual symptoms .

Hervé Hoppenot: The first one is residual symptoms, not as significant as it is in MF, but residual symptoms. The second consequence is residual thrombotic risk. The third consequence is residual transformational risk. 989 solves the problems that HU created. Even in a second line single agent study or with those data, I expect that 989 will reshape the use of hydroxyurea, where patients transition off of therapy rapidly. Because 989 is targeting disease-causing cells, it is better tolerated. For example, HU has seven warnings and precautions and it is easier to dose. The market for ET is about $5 billion. ET MKLR patients, roughly half of them are resistant or intolerant to therapy. There is a clear glide path to growth in ET with the first study. As it relates to MF, it is of course a completely different type of MPN.

Speaker #5: The second consequence is residual thrombotic risk . And the third consequence is residual transformational risk . 989 solves the problems that Hugh created .

It's better tolerated for example, H use got seven warnings and precautions and it's easier it's easier to dose the.

Speaker #5: And even in a second line , single agent study or with those data , I expect that 989 will reshape the use of hydroxyurea where patients transition off of therapy rapidly because 989 is targeting disease causing cells .

The market for <unk> is about $5 billion.

E T M <unk> patients rough.

Roughly half of them are resistant or intolerant to therapy, and so I think there is a clear glide path to growth and E. T. With the first study and then as it relates to MF. It's of course, a completely different type.

Speaker #5: It's better tolerated . For example , who's got seven warnings and precautions ? And it's easier . It's easier to dose the market for ET is about $5 billion ET patients , roughly half of them are resistant or intolerant to therapy .

Of M. P N the risk of transformation to leukemia is real it's more aggressive it's more symptomatic.

As effective as Jakafi is.

Speaker #5: And so I think there's a clear glide path to growth in ET with the first study . And then as it relates to MF , it's of course a completely different type of MPN .

As you know the SVR 35 is between 30% and 40% alright symptoms are in the mid fifties everybody.

On Jakafi progresses.

And so even in the second line setting there is going to be just like E. T. The move to either add 989 will have to of course produce that data or use at 989. After after jakafi and I think that the opportunity in both MF and E. T is fairly significant and what we're looking to.

Speaker #5: The risk of transformation to leukemia is real . It's more aggressive , it's more asymptomatic . As effective as jakafi is , as you know , the SVR 35 is between 30 and 40% .

Hervé Hoppenot: The risk of transformation to leukemia is real, it is more aggressive, it is more symptomatic. As effective as Jakafi is, as you know, the SVR 35 is between 30% and 40%. Symptoms are in the mid-50%. Everybody on Jakafi progresses. Even in a second line setting there is going to be, just like in ET, a move to either add 989, we will have to of course produce that data, or use 989 after Jakafi. The opportunity in both MF and ET is fairly significant. We are looking to build a business well into the next decade. If we start the studies in the middle of 2026, give or take, we should be getting out sometime in that 2029-2030 period. Thanks for the question.

Speaker #5: Right . Symptoms are in the mid 50s . Everybody on Jakafi progresses . And so even in a second line setting , there is going to be just like an ET .

To build a business well into the next decade, if we start the studies in the middle of a middle of 'twenty six give or take we should be getting out some time in that 29 30 period.

Speaker #5: A move to either add 989 . We'll have to of course produce that data or use 989 after after jakafi . And I think that the opportunity in both MF and ET is fairly significant .

Thanks for the question.

Thank you next question today is coming from Sal being Ritchie from Goldman Sachs. Your line is now live.

Speaker #5: And what we're looking to is build a business well into the next decade . If we start the studies in the middle of of middle of 26 , give or take , we should be getting out sometime in that 2930 period .

Good morning, Thanks for taking my.

<unk> you've highlighted for us that's an important part of the and tell our story in terms of the MTN story in terms of the drugs being in functional cure and just remind us what you want to see on the bathroom adoption and level set us on how well understood. The ultimate correlation is between staff and clinical outcomes.

Speaker #5: Thanks for the question .

Speaker #2: Thank you . Next question today is coming from Salveen Richter from Goldman Sachs . Your line is now live .

Alexis Smith: Thank you. Next question today is coming from Sabine Richter from Goldman Sachs. Line is now live.

Speaker #14: Good morning . Thanks for taking my questions . You've highlighted Vaf as an important part of the story in terms or the MPN story in terms of the drug being a functional cure and just remind us what you want to see on Vaf reduction and level .

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

And just a second question here Bill.

Your you highlighted your focus on managing operating expenses and streamlining the company.

Are you thinking about the evolution of the company's target margin profile over the next two years and also through the Jakafi elderly. Thank you.

Speaker #14: Set us on how well understood the ultimate correlation is between Vaf and clinical outcomes . And just a second question here , Bill , on , you know , your you've highlighted your focus on managing operating expenses and streamlining the company .

Great I'll turn the first question Sal being about molecular response over to Pablo and then I'll address your question about Opex after that.

Thank you for the question is how long until we have three and it's important to remember we're up three molecular endpoints that we're going to report data on before the end of the year, one as vas and whole blood.

Speaker #14: How are you thinking about the evolution of the company's target margin profile over the next few years ? And also through the low ?

Speaker #14: Thank you .

One is CD 34 positive mutant call ourselves in peripheral blood mononuclear cells and the third is malignant Mega carriage has from you didn't call army of characters in the bone marrow and the reason why emphasizing those three because <unk> is a relative in a way a lagging indicator of what's happening in the bone marrow, which is true.

Speaker #5: Great . I'll turn the first question salveen about molecular response over to Tableau . And then I'll address your question about opex . After that .

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

Speaker #6: Thank you for the question . So we have three . And it's important to remember we have three molecular endpoints that we're going to report data on before the end of the year .

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

Speaker #6: One is vaf in whole blood . The other one is Cd34 positive mutant color cells in peripheral blood mononuclear cells . And the third is malignant megakaryocytes or mutant color in the bone marrow .

All the matters the disease originates in the bone marrow and reducing malignant mega carriers, such in the bone marrow, which is something we showed for E. T. DHA. This year is the critical disease modifying effect that then will translate into a reduction of CD 34 positive mutant color palettes yourselves.

Speaker #6: And the reason why I emphasize in those three is because vaf is a in a way , a lagging indicator of what's happening in the bone marrow , which is what truly matters .

Peripheral blood and that in turn over time will be reflected in a reduction in vas.

Speaker #6: The disease originates in the bone marrow, and reducing malignant megakaryocytes in the bone marrow is something we showed for ETI, a day.

Pablo Cagnoni: The disease originates in the bone marrow, and reducing malignant megakaryocytes in the bone marrow, which is something we showed for ET at EHA this year, is the critical disease-modifying effect that then will translate into reduction of CD34 positive mutant CALR positive cells in peripheral blood, and that in turn over time will be reflected in a reduction in VAF. I think I would emphasize that it's important to look at all three components of the translational endpoints, and we'll talk about all three before the end of the year. In terms of correlations, we know that high VAF is a bad thing, and we've shown some data in ET that patients with lower VAF that would put slightly higher VAF reductions over time have better hematologic responses in ET, et cetera. That data are important.

So I think I would emphasize that it's important to look at all three components of the translational nine points I will talk about all three before the end of the year in terms of correlations.

Speaker #6: This year, it is the critical decision modifying effect that then will translate into a reduction of CD34-positive mutant color-positive cells in peripheral blood.

Look we know that have vas as a bad thing and we've showed some data in E T that patients with lower Vas that.

Speaker #6: And that in turn , over time will be reflected in a reduction in vaf . So I think I would emphasize that it's important to look at all three components of the translational endpoints .

Slightly higher back reductions over time.

<unk>.

Router hematologic responses in E. T that data are important we still believe that more likely than not initial approvals for 99 will be based fundamentally on clinical endpoints traditional clinical endpoints a combination of the endpoints that we know which are spleen symptoms and anemia and that's the way we're bill.

Speaker #6: And we'll talk about all three before the end of the year . In terms of correlations . Look , we know that have vaf is a bad thing .

Speaker #6: And we've shown some data in ET that patients with lower VAF that would slightly higher VAF reductions over time have better hematologic responses in ET.

Then there's pivotal trials for next year I'll pass it back to Bill Yeah, Thanks, Pablo and as it relates to Opex Avi and it's a good question and I spent a lot of time thinking about it and as you implied in your question.

Speaker #6: That data are important. We still believe that, more likely than not, initial approvals for 99 will be based fundamentally on clinical endpoints.

Pablo Cagnoni: We still believe that more likely than not, initial approvals for 989 will be based fundamentally on clinical endpoints, traditional clinical endpoints, a combination of the endpoints that we know, which are spleen, symptoms, and anemia. That's the way we're building this pivotal trial for next year. I'll pass it back to Bill.

We have to take a multi week multi year view of the of the budget and I am not necessarily hard coating for opex as a percentage or R&D as a percentage of sales, but I do expect that the quantum.

Speaker #6: Traditional clinical endpoints a combination of endpoints that we know which are spleen symptoms and anemia . And that's the way we're building this pivotal trials for next year .

Speaker #6: I'll pass it back to Bill.

Speaker #5: Yeah . Thanks , Pablo . And as it relates to OpEx , it's a good question . I spent a lot of time thinking about it .

Hervé Hoppenot: Yeah, thanks, Pablo. As it relates to OpEx, Salvine, it's a good question. I spent a lot of time thinking about it, and as you implied in your question, we have to take a multi-year view of the budget. I'm not necessarily hard coding for OpEx as a % or R&D as a % of sales, but I do expect that the quantum of at least spending growth or the % is going to come down. I expect it to come down because of increase in sales and leverage. Here's what I will say. Every R&D dollar and every SG&A dollar has to serve a business strategy, and budgeting is about distinguishing the high value projects, as you know, from the low value projects. Another way to put it is good costs from bad costs.

At least.

Spending growth or the percentage is going to come down in <unk>.

Speaker #5: And as you implied in your question , we have to take a multi multi-year view of the of the budget . And I'm not necessarily hard coding for opex as a percentage or R&D as a percentage of sales .

I expect it to come down because of an increase in sales and leverage.

Here's what I will say every R&D dollar and every SG&A dollar has the server business strategy and budgeting is about distinguishing the high value projects as you know from the low value projects or another way to put it is good costs from some from bad costs, what we're really solving for though is creating the steepest growth curve possible.

Speaker #5: But I do expect that the quantum of at least spending growth or the percentage is going to come down and I expect it to come down because of an increase in sales and leverage .

Post 'twenty nine and a long duration revenue and cash flow stream, we will streamline costs, where possible, but not underfund critical initiatives and compromise growth and that is those are the principles as I think about opex and I do expect our margins to improve over time.

Speaker #5: Here's what I will say . Every R&D dollar and every dollar has to serve a business strategy . And budgeting is about distinguishing the high value projects .

Speaker #5: As you know , from the low value projects or another way to put it is good costs from some , from bad costs .

Speaker #5: What we're really solving for , though , is creating the steepest growth curve possible . Post 29 and a long duration revenue and cash flow stream .

Hervé Hoppenot: What we're really solving for is creating the steepest growth curve possible post 2029 and a long duration revenue and cash flow stream. We will streamline costs where possible, but not underfund critical initiatives and compromise growth. Those are the principles as I think about OpEx, and I do expect our margins to improve over time, in part due to increasing sales and good, good cost control. Thanks for the question.

In part due to increasing sales and.

Good good cost control.

Thanks for the question.

Thank you. Your next question today is coming from Peter Lawson from Barclays. Your line is alive.

Speaker #5: We will streamline costs where possible , but not underfund critical initiatives and compromise growth . And that is , those are the principles , as I think about opex .

Thanks for taking the questions.

The.

St Louise.

Speaker #5: And I do expect our margins to improve over time , in part due to increasing sales and good , good cost control . Thanks for the question .

Is the trajectory of that growth was really impressive this quarter and I was wondering if you could also talk us around the profitability of that franchise.

Peter could you just repeat the question was a little hard to hear Oh, Yes, I'm, sorry, Nick timber.

Speaker #2: Thank you . Next question today is coming from Peter Lawson from Barclays . Your line is now live .

Alexis Smith: you. The next question today is coming from Peter Lawson from Barclays. Your line is now live.

Speaker #15: Great . Thanks for taking the questions . Nick . Timbo , kind of how sustainable is the is the trajectory on that growth is really impressive for this quarter .

Pablo Cagnoni: Great, thanks for taking the questions. Naktimvo, how sustainable is the trajectory on that growth? It was really impressive this quarter, and wonder if you could also talk around the profitability of that franchise.

Got to get through the sustainability of the trajectory. It was really impressive this quarter and if you can talk through.

The profitability as well.

Yeah, I'll start off and if if Mohammad who runs that business has any any additional comments.

Speaker #15: And wonder if you could also talk around the profitability of that franchise .

He can contribute to <unk>.

Speaker #5: Peter , could you just repeat the question . It was a little hard to hear .

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

Youre right its off to a very very good start.

Speaker #15: Oh yeah . Sorry , Nick . Tim , if you could talk through the sustainability of the trajectory , it was really impressive this quarter .

Pablo Cagnoni: Oh yeah, sorry.

Steven Stein: On Naktimvo, if you could talk through the sustainability of the trajectory.

We're annualizing almost at $200 million a year I think the important the important.

Pablo Cagnoni: It was really impressive this quarter, and if you talk through the profitability as well.

Speaker #15: And if you could talk through the profitability as well .

The important point about the launch right now as you have virtually every BMT center in the United States, using and purchasing the timber which I think is very very encouraging all the feedback we've got from transplant or as is is very very positive.

Speaker #5: Yeah , I'll start off . And if if Mohammed , who runs that business has any any additional comments , he can contribute to .

Hervé Hoppenot: Yeah, I'll start off. If Mohamed, who runs that business, has any additional comments, he can contribute too. You're right. It's off to a very, very good start. We're annualizing almost at $200 million a year. I think the important point about the launch right now is you have virtually every BMT center in the United States using and purchasing Naktimvo, which I think is very, very encouraging. All the feedback we've got from transplanters is very, very positive. As you know, we're in the third, fourth quarter of a launch, and launches early on can be unpredictable from quarter to quarter. All I can tell you is I think the growth trajectory of this is solid right now. If you look at the Resarock curve when it launched, we're virtually right on top of it.

Speaker #5: You're right . It's off to a very , very good start . You know , we're annualizing almost at at $200 million a year .

As you know we're in the third and fourth quarter of a launch and launches early on can be unpredictable from from quarter to quarter. All I can tell you is I think the growth trajectory of this is solid right now if you look at the.

Speaker #5: I think the important the important , the important point about the launch right now is you do have virtually every BMT center in the United States .

Speaker #5: Using and purchasing Nick Timbo , which I think is is very , very encouraging . All the feedback we've got from Transplanters is , is very , very positive .

Reza Roc curve.

When it launched where we're virtually right on top of it that products you know they had a tough quarter.

Speaker #5: As you know, we're in the third and fourth quarter of a launch, and launches early on can be unpredictable from quarter to quarter.

But it's roughly a $500 million business.

In terms, so I think the prospects for growth next year, our solid we'll of course share guidance.

Speaker #5: All I can tell you is I think the growth trajectory of this is solid right now . If you look at the ROC curve , when it launched , we're we're virtually right on top of it .

In early 2026, but I don't see any.

Red flags right now other than launches can be a little bit unpredictable and uncertain, but I like the way it looks.

Speaker #5: That products . You know they had a tough quarter . But it's roughly a $500 million business . So I think the prospects for growth next year are solid .

Hervé Hoppenot: That product, you know, they had a tough quarter, but it's roughly a $500 million business. I think the prospects for growth next year are solid. We'll, of course, share guidance in early 2026. I don't see any red flags right now other than launches can be a little bit unpredictable and uncertain. I like the way it looks. The next comment I would make as it relates to profitability. One of the nice things about this product is, especially this product, we're not covering 10,000, 20,000, 30,000 physicians or several thousand hospitals. We have a very targeted audience of BMT centers across the United States. When you look at the margin profile, a product like this, it's very healthy. That's what I can tell you about profitability. I wish more of them were as profitable as Naktimvo. Mohamed, do you have anything you want to add?

The next comment I would make as it relates to profitability you know one of the.

One of the nice things about this product because it's a specialty product and we're not covering.

Speaker #5: Well, of course, share guidance in early 2026. But I don't see any red flags right now, other than launches can be a little bit unpredictable and uncertain.

10000, 20000, 30000 physicians or several thousand hospitals, we have a very.

Speaker #5: But I like the way it looks . The next comment I would make as it relates to profitability , you know , one of the one of the nice things about this product is it's especially product .

Targeted audience.

Of BMT centers across the United States and so when you look at the margin profile a product like this.

It's very healthy that's what I can tell you about profitability I wish more of them were as profitable as Nick timber Baja.

Speaker #5: And we're not covering 10,000 , 20,000 , 30,000 physicians or several thousand hospitals . We have a very targeted audience of BMT centers across the United States .

Bahama do you have anything you want to add yes. Thanks, Bill maybe just to complement and give you some color on the sustainability of the growth you know as Bill mentioned, a really broad penetration with 90% of transplant centers pick.

Speaker #5: And so when you look at the margin profile of product like this , it's it's very healthy . That's what I can tell you about profitability .

Picking up Nick Tembo, but we're seeing all of them have repeat orders year to date, which speaks not only to the trial utilization, but the repeat utilization within these accounts and the feedback.

Speaker #5: I wish more of them were as profitable as Nick , Timbo , Mohammed , do you have anything you want to add ?

Speaker #16: Yeah . Thanks , Bill . Maybe just to compliment and give you some color on the sustainability of the growth . You know , as Bill mentioned , a really broad penetration with 90% of transplant centers picking up .

Mohamed Issa: Yeah, thanks, Bill. Maybe just to complement and give you some color on the sustainability of the growth. You know, as Bill mentioned, a really broad penetration with 90% of transplant centers picking up Naktimvo. We're seeing all of them have repeat orders year to date, which speaks not only to the trial utilization, but the repeat utilization within these accounts. The feedback continues to be positive. Another point on the sustainability of the trajectory is in line with our expectations. Most of the utilization today is happening in the fourth line, but we're seeing a lot more preference and increasing preference in the third line setting, which gives us a lot of headroom left to go. Maybe one last point on the sustainability. You know, our goal that we communicated on the last call was to have about 1,000 active patients on therapy by the end of the year.

<unk> to be positive another point on the sustainability of the trajectory is in line with our expectations. Most of the utilization today is happening in the fourth line, but we're seeing a lot more preference and increasing preference in the third line setting, which gives us a lot of headroom left to go and maybe one last point on the sustainability.

Speaker #16: Nick Timbo . But we're seeing all of them have repeat orders year to date , which speaks not only to the trial utilization , but the repeat utilization within these accounts and the feedback continues to be positive .

<unk> you know our goal that we communicated on the last call was to have.

Speaker #16: Another point on the sustainability of the trajectory is in line with our expectations . Most of the utilization today is happening in the fourth line , but we're seeing a lot more preference and increasing preference in the third line setting , which gives us a lot of headroom left to go .

About 1000 active patients on therapy by the end of the year through the first nine months, we have about 800 or so patients well on our way to that thousand patient goal by the end of the year and that continues to be promising as well and then from a contribution margin maybe just the last note as you know this this contribution margin for the Knick Tembo P&L.

Speaker #16: And maybe one last point on the sustainability , you know , our goal that we communicated on the last call was to have about 1000 active patients on therapy by the end of the year .

<unk> is one of the higher in our portfolios and we expect it to continue to be such given the level of focus that we have on the product and the level of focus from a commercial execution great. Thanks Mohamad. Thanks for the question Peter.

Speaker #16: Through the first nine months , we have about 800 or so patients . Well on our way to that thousand patient goal . By the end of the year .

Mohamed Issa: Through the first nine months, we have about 800 or so patients, well on our way to that 1,000 patient goal by the end of the year, and that continues to be promising as well. From a contribution margin, maybe just the last note is, this contribution margin for the Naktimvo P&L is one of the higher in our portfolios, and we expect it to continue to be such given the level of focus that we have on the product and the level of focus from a commercial execution.

Speaker #16: And that continues to be promising as well . And then from a contribution margin , maybe just the last note is , you know , this this contribution margin for the Nick PNL is one of the higher in our portfolios .

Thank you. Your next question is coming from Evan <unk> from BMO capital markets. Your line is now live.

Hi, guys. Thanks for taking the question great to see a lot of you at ESMO, but I think we'd all agree that <unk> is a very critical juncture for insight, but I want to take it out of the picture for a second so can you walk me through how the current pipeline east needs to mature to drive growth through the Jakafi low.

Speaker #16: And we expect it to continue to be such given the level of focus that we have on the product and the level of focus from a commercial execution .

Speaker #5: Great . Thanks , Mohammed . Thanks for the question , Peter .

Hervé Hoppenot: Great. Thanks, Mohamed. Thanks for the question, Peter.

Speaker #2: Thank you . Next question is coming from Evan Sugerman from BMO Capital Markets . Your line is now live .

Alexis Smith: Thank you. Next question is coming from Evan Seigerman from BMO Capital Markets. Your line is now live.

And then what type of business development, you're not going to be specific but would you have to do to help also supplement that growth essentially I want to understand what insight looks like with and without <unk> by the end of the decade. Thank you so much.

Speaker #17: Hi , guys . Thanks for taking the question . Great to see a lot of you at home . So I think we'd all agree that McKellar is a very critical juncture for insight , but I want to take it out of the picture for a second .

Mohamed Issa: Hi guys, thanks for taking the question.

Pablo Cagnoni: Great to see a lot of you at ESMO.

Mohamed Issa: I think we'd all agree that Naktimvo is a very critical juncture for Incyte, but I want to take it.

Pablo Cagnoni: Out of the picture for a second. Can you walk me through how.

Thanks for the question, Evan, Yes, and it was nice to see you at ESMO too.

Speaker #17: So can you walk me through how the current pipeline needs to needs to mature to drive growth through the low , and then what type of business development you're not going to be specific , but would you have to do to help ?

Mohamed Issa: The current pipeline needs to mature to drive growth through the Jakafi LOE, and then what type of business development you're.

Here's here's how I would look at the pipeline we're focused on.

Pablo Cagnoni: Not going to be specific, but would.

Seven drivers seven projects that I think have the potential to create very meaningful value.

Mohamed Issa: you have to do to help also supplement that growth?

Speaker #17: Also supplement that growth ? Essentially , I want to understand what insight looks like with and without McKellar . By the end of the decade .

Pablo Cagnoni: Essentially, I want to understand what Incyte insight.

Mohamed Issa: Looks like with and without MCLR by.

And not all of them have to work not all of them will work, we're not going to be we're not going to be perfect, but we have <unk>, which is a three indication product.

Pablo Cagnoni: The end of the decade. Thank you so much.

Speaker #17: Thank you so much .

Speaker #5: Thanks for the question , Evan . Yes , and it was nice to see you at Ismo to here's here's how I would look at the pipeline .

Hervé Hoppenot: Thanks for the question, Evan. Yes, and it was nice to see you at ESMO too. Here's how I would look at the pipeline. We're focused on seven drivers, seven projects that I think have the potential to create very meaningful value. Not all of them have to work, not all of them will work. We're not going to be perfect. We have povorcitinib, which is a three-indication product. We can build a JAK-anchored franchise in dermatology where we have differentiated knowledge and capabilities and a very solid data set. The second project is 989, and I can't take it out of the picture, Evan. That's an important project. We have 617F, which is still an early stage, a little bit more opaque, but as we de-risk that asset, that could be as big or bigger than 989 in MPNs because it's covering a mutation that's much more frequent.

We can build a jack anchored franchise in dermatology, where we have differentiated knowledge and capabilities in a very solid dataset.

Speaker #5: We're focused on seven drivers , seven projects that I think have the potential to create very meaningful value . And not all of them have to work .

The second project is 989 and I can't take it out of the picture even okay. That's an important project. We have 617, which is still in early stage a little bit more opaque, but is that as we derisk that asset that could be as big or bigger.

Speaker #5: Not all of them will work . We're not going to be we're not going to be perfect . But we have positive , which is a three indication product we can build a jack anchored franchise in dermatology , where we have differentiated knowledge and capabilities and a very solid data set .

Then 989 in M P and because its covering a mutation that's much more much more frequent in fact, it could be two exercise of a 989.

Speaker #5: The the second project is 989 , and I can't take it out of the picture . Evan . Okay , that's an important project .

Then we have three solid tumor programs, which we derisked at ESMO, we still have more data to collect you'll have GE <unk> pancreatic cancer TGF by PD, one for CRC and CDK to for ovarian cancer, but I would say here is that we're systematically and deliberately.

Speaker #5: We have 617 , which is still in early stage , a little bit more opaque , but as that as we de-risk that asset , that could be as big or bigger than 989 in Npns because it's covering a mutation that's much more , much more frequent .

Speaker #5: In fact , it could be two exercise of a 989 . Then we have three solid tumor programs , which we de-risked at ESMO .

Hervé Hoppenot: In fact, it could be 2x the size of 989. Then we have three solid tumor programs, which we de-risked at ESMO. We still have more data to collect. You have KRASG12D for pancreatic cancer, TGFβR2 by PD-1 bispecific antibody for CRC, and CDK2 inhibitor for ovarian cancer. What I would say here is that we're systematically and deliberately, and at least up until ESMO, quietly building a high-impact oncology portfolio. There is a lot of substrate there. I don't expect all these necessarily to work. If one or two of those hit, they could be very, very meaningful. As we talked about at the start of the call, novel compounds against novel biological targets in cancers that have missed the IO revolution where there's significant medical need. We're positioning all three compounds frontline in combination with standard of care chemo. The seventh project that I focus on is Naktimvo.

And at least up until ESMO.

Quietly building.

A high impact oncology portfolio. There is a lot of substrate, there and I expect all of these necessarily to work alright, but if one or two of those hit they could be very very meaningful as we talked about at the start of the call novel compounds against novel biological targets.

Speaker #5: We still have more data to collect . You have g12d pancreatic cancer , TGF by PD one for CRC and Cdk2 for ovarian , ovarian cancer .

Speaker #5: But I would say here is that we're systematically and deliberately, and at least up until ESMO, quietly building a high-impact oncology portfolio.

In cancers that are missed the Io Revolution, where there is significant.

Speaker #5: There is a lot of substrate there . I don't expect all these necessarily to work right . But if 1 or 2 of those hit , they could be very , very meaningful .

Medical need.

And we're positioning all three compounds frontline.

In combination with standard of care chemo.

Speaker #5: As we talked about at the start of the call, novel compounds against novel biological targets in cancers that have missed the IO revolution, where there's significant medical need, and we're positioning all three compounds front line in combination with standard of care, chemo. And then the seventh project that I focus on is Nick, Timbo.

And then the seven project that I focus on is Nick timber and as Muhammad talked about.

After a good start and there was a question about sustainability, we have two combination trials in place.

If one of those commentary combination trials hit and we're one for two we moved this into the second line. If its the combination trial with Jakafi. We are a non steroid regimen and you could two extra value that's the value of that business.

Speaker #5: And as Mohammed talked about , we're off to a good start . And there was a question about sustainability . We have two combination trials in place .

Hervé Hoppenot: As Mohamed talked about, we're off to a good start. There was a question about sustainability. We have two combination trials in place. If one of those combination trials hit, we're one for two. We move this into the second line. If it's the combination trial with Jakafi, we have a non-steroid regimen, and you could 2x the value of that business. When you think about the flow across all of our three verticals, immunology, hematology, and oncology, there's some real substrate there, and we don't need to be perfect. We just need two or three of these out of the seven to hit, and we'll build a business that's bigger than the one that we have post 2029. Thanks for the question.

And so when you think about.

The flow across all of our three verticals ini hematology and oncology, there's some real substrate, there and we don't need to be perfect. We just need two or three of these out of the seven to hit and we'll build a business that's bigger than the one that we have post 2029, thanks for the <unk>.

Speaker #5: If one of those common combination trials hit , we're one for two . We move this into the second line . If it's the combination trial with Jakafi , we have a Non-steroid regimen , and you could twoex the value .

Speaker #5: The value of that business . And so when you think about the flow across all of our three verticals , I and I , hematology and oncology , there's some real substrate there .

Sure.

Thank you. Your next question today is coming from Jared Shaw from Wells Fargo. Your line is now live.

Hey, good morning, and thanks for taking the questions.

Speaker #5: And we don't need to be perfect . We just need 2 or 3 of these . Out of the seven to hit . And we'll build a business that's bigger than the one that we have .

Just curious for 989 pivotal trials in <unk>.

<unk> expected next year.

With IV or with the on body pumps on MTS.

Speaker #5: Post 2029 . Thanks for the question .

And then just a quick follow up in terms of a potential <unk> launch in Canada.

Speaker #2: Thank you . Next question today is coming from Derek Archilla from Wells Fargo . Your line is now live .

Alexis Smith: Thank you. Next question today is coming from Derek Cartillo from Wells Fargo. Your line is now live.

Commentary around the launch plans in the prepared remarks, I guess, how do you plan to position with payers and I guess, what's your base case in terms of the amount of shares you can convert from from Jakafi Collegian Alex. Thanks.

Speaker #18: Hey good morning and thanks for taking the questions . I'm just curious for nine pivotal trials in MF and expected next year , will these be with IV or with the on body pump from infuse .

Pablo Cagnoni: Hey, good morning and thanks for taking the questions. Just curious for 989's pivotal trials in MF and ET expected next year. Will these be with IV or with the on-body pump from Enfuse?

Yeah. Good question I'll make a few comments about enable and XR and then ask.

Speaker #18: And then just a quick follow up in terms of a potential XR launch and kind of , you know , commentary around the launch plans in the prepared remarks , I guess , how do you plan to position with payers ?

Mohamed Issa: Just a quick follow up in.

Rob Lowe and Muhammad.

Pablo Cagnoni: terms of a potential XR launch and, you know, commentary around the launch plans in the prepared remarks, I guess how do you plan to position with payers, and I guess what's your base case in terms of the amount of shares you can convert from Jakafi pre-generics? Thanks.

First we're really pleased to strike a partnership with with enable they specialize in.

In.

Speaker #18: And I guess what's your base case in terms of the amount of share you can convert from ? From pre generics ? Thanks .

High volume subcutaneous administration.

Products with a range of five ml that 25 ml.

Speaker #5: Yeah . Good question . I'll make a few comments about enable and XR and then ask Pablo and Mohammed . First we're really pleased to strike a partnership with with enable .

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

We also like the device because it's at home self administered.

Comfort.

The efficiency of their manufacturing manufacturing operation.

Speaker #5: They specialize in high volume subcutaneous administration with you know , products with a range of five ML to 25 ML . We also like the device because it's at home , self-administered comfort , the efficiency of their their manufacturing , manufacturing operation .

And I think it's a high quality company, they're expanding their manufacturing site, which is an FDA approved manufacturing site and they have commercial devices I think in roughly 25 countries and about 8000 units and so this is there is a high quality company.

Pablo can talk more about the program as it relates to X or.

Speaker #5: And I think it's a high quality company . They're expanding their manufacturing site , which is an FDA approved manufacturing site , and they have commercial devices .

Let's just.

Pablo why don't you speak and then we'll go to XR.

So in terms of their plan to incorporating and fuse into the pivotal trials in M. P ends.

Speaker #5: I think in roughly 25 countries and about 8000 units . And so this is this is a high quality company . Pablo can talk more about the program as it relates to XR .

E T is pretty far along we showed an update our I D.

H a few months ago on the date of the data has continued to mature we have already initiated regulatory interactions around that so we're probably going to be ready to start pivotal trial in E. T. Before we're ready to deploy the infused device for.

Speaker #5: Well, let's just go to Pablo. Why don't you speak, and then we'll go to XR.

Speaker #6: So in terms of the plan to incorporating infuse into the pivotal trials in Npns , you know , ET is pretty far along .

Pablo Cagnoni: In terms of the plan to incorporating ENTHUSE into the pivotal trials and MPNs, you know ET is pretty far along. We showed an update at EHA a few months ago on the data. The data has continued to mature. We have already initiated regulatory interactions around that. We're probably going to be ready to start pivotal trial in ET before we're ready to deploy the infused device for MF. The goal is to as quickly as possible make the infused device available and ready to go so we can start those studies with the subq administration. However, I can be firm at this point. We need a little bit more time to really figure out the timing for the implementation of this, but that would be our goal for MF.

<unk> goal is to as quickly as possible make the infused device available and ready to go. So we can start those studies.

Speaker #6: We showed an update at Iaha a few months ago on the data . The data has continued to mature . We have already initiated regulatory interactions around that , so we're probably going to be ready to start pivotal trial in ET before we're ready to deploy the infused device for MF .

The sub Q administration, however, I can be firm at that point at this point, we need a little bit more time to really figure out the timing for the implementation of this but that would be our goal for them at good Mohamad.

How many you want to talk about XOR, yeah, if I can put that in frame for us real quick Derek Jakafi or <unk> represents a great addition to the portfolio are expected to launch in the middle part of 2026, Hep's and patients now are going to have a convenient once daily formulation of a brand that they know and trust we expect about 15 to 30.

Speaker #6: The goal is to as quickly as possible , make the infused device available and ready to go so we can start those studies with the Subcu administration .

Speaker #6: However , I can be firm at that at this point . We need a little bit more time to really figure out the timing for the implementation of this , but that would be our goal for MF .

Speaker #5: Good . Mohammed , you want to talk about XR ?

Hervé Hoppenot: Good. Mohamed, you want to talk about XR?

Sent conversion from the IR by 2028, and with a slower erosion curve than <unk> XR can be a solid incremental contributor to top line sales through 2030 and beyond and as you mentioned look our our launch strategy is focused on securing quick formulary access accelerating HCP adoption.

Speaker #16: Yeah . If I can put that in frame for for us real quick , Derek Jakafi XR as you know , represents a great addition to the portfolio expected to launch in the middle part of 2026 .

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

Speaker #16: Hcp's and patients now are going to have a convenient once daily formulation of a brand that they know and trust . We expect about 15 to 30% conversion from the IR by 2028 , and with a slower erosion curve than IR .

And patient preference to maximize that uptick in the short term for that long term value and if I can just point to our ability to launch Nick Tembo, FL and <unk> and <unk> S. The AC I'm just proud of our team's ability to execute on these launches and I think XR wont be any different.

Speaker #16: XR can be a solid incremental contributor to top line sales through 2030 and beyond . And as you mentioned , look , our launch strategy is focused on securing quick formulary access , accelerating HCP adoption and patient preference to maximize that uptake in the short term for that long term value .

Great. Thanks Mohamad thanks for the question.

Thank you next question today is coming from Ashwin <unk> from UBS. Your line is now live.

Speaker #16: And if I can just point to our ability to launch Nick Timbo FL in Monjuvi and zinus and SCC , I'm just proud of our team's ability to execute on these launches .

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

Hi, Thanks for taking our questions as well so yes, a lot of focus on 989, maybe just like looking at the slide 22, and defense I think that next building.

Speaker #16: And I think XR won't be any different .

DNS, but just wanted to confirm at this point are you able to pursue first line are naive patients in registration studies.

Speaker #5: Great . Thanks , Mohamad . Thanks for the question .

Hervé Hoppenot: Great. Thanks, Mohamed. Thanks for the question.

Speaker #2: Thank you . Next question . Today is coming from Ash Verma from UBS . Your line is now live . .

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

And then secondly on the formulation like Oh.

Speaker #19: Hi . Thanks for taking our questions as well . So yeah , a lot of focus on nine eight , nine maybe just looking at the slide 20 a few different settings that you're exploring in ET and MF , but just wanted to confirm at this point .

Operator: Hi, thanks for taking our questions as well.

Are you able to get the volume down to like how many of them and is this something that can be a home sub Q injection and not just an on body Foundation.

Pablo Cagnoni: Yes, a lot of focus on 989.

Operator: Maybe just like looking at the slide.

Pablo Cagnoni: A few different settings that you're exploring in ET and MF. Just wanted to confirm at this point, are you able to pursue first-line or naive patients in registration studies? Secondly, on the formulation, where are you able to get the volume down to, like how many mL? Is this something that can be a home sub Q injection and not just an on-body formulation? Thanks.

<unk>.

As probably you want to take that.

Speaker #19: Are you able to pursue first line or naive patients in in registrational studies . And then secondly on the formulation like where are you able to get the volume down to like how many ML and is this something that can be a home ?

Certainly thank you for the question. So I think the first part was about first line.

And the answer is we fully intend to develop <unk> 99 for first line patients with myelofibrosis. That's why we're running the combination with rux led NAV.

Speaker #19: Subq injection and not just an onboarding formulation ? Thanks .

Treatment naive patients Dod work is ongoing we're not going to disclose the results on that before the end of this year, but I'm confident that we will find a path. There are we have very clear preclinical data showing synergy between 99 and Brooks, let nib and the right models of MF. So I'm confident that we will find a path.

Speaker #5: Thanks , ash . Pablo , you want to take that ?

Hervé Hoppenot: Thanks, Ash. Pablo, you want to take that?

Speaker #6: Certainly . Thank you for the question . So I think the first part was about first line . And the answer is we fully intend to develop 989 for first line patients with myelofibrosis .

Pablo Cagnoni: Certainly. Thank you for the question. I think the first part was about first-line MF, and the answer is we fully intend to develop 989 for first-line patients with myelofibrosis. That's why we're running the combination with ruxolitinib in treatment-naive patients. That work is ongoing. We're not going to disclose results on that before the end of this year, but I'm confident that we will find a path there. We have very clear preclinical data showing synergy between 989 and ruxolitinib in the right models of MF. I'm confident that we will find a path there. In terms of the sub Q, our goal is to have a device that patients can use at home for self-administration of 989 subcutaneously. That's the goal. That's why we put in place a collaboration with Enable, and we think we're going to find a path to that in 2026.

Speaker #6: That's why we're running the combination with the Ruxolitinib in treatment naive patients . That work is ongoing . We're not going to disclose results on that before the end of this year .

In terms of the South Q. Our goal is to have a device that patients can use at home for self administration of 99 subcutaneously. That's the goal. That's why we are putting place a collaboration with enable and we think we're going to find a path for that in 2026. Thanks. Pablo next question. Thank you next question.

Speaker #6: But I'm confident that we will find a path there . We have very clear preclinical data showing synergy between 900 and 9 and Ruxolitinib in the right models of MF .

Speaker #6: So I'm confident that we will find a path there in terms of the subcu , our goal is to have a device that patients can use at home for self-administration of 909 subcutaneously .

<unk> today is coming from Ren Benjamin from citizens. Your line is now live.

Hey, good morning, guys. Thanks for taking the questions and congratulations on a great quarter I guess just to follow up with Rux XR. There were there was a strategy way back when about combining it with a pipeline product to help fight. This low we are or are you looking at any potential combinations to move this forward with either of the pipeline.

Speaker #6: That's the goal . That's why we we put in place a collaboration with enable , and we think we're going to find a path for that in 2026 .

Speaker #5: Thanks , Pablo . Next question .

Hervé Hoppenot: Thanks, Pablo. Next question.

Speaker #2: Thank you. Next question today is coming from Benjamin from Citizens. Your line is now live.

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

Or in licensing of <unk>.

Speaker #20: Hey good morning guys . Thanks for taking the questions and congratulations on a great quarter . I guess just to follow up with Rux , XR , there was a strategy way back when about combining it with a pipeline product to help kind of fight this low .

Hervé Hoppenot: Hey, good morning guys. Thanks for taking the questions and congratulations on a great. I guess just to follow up with ruxolitinib XR, there was a strategy way back when about combining it with a pipeline product to help kind of fight this loss. Are you looking at any potential combinations to move this forward with either the pipeline or, you know, in-licensing a product and, you know, staving off this erosion curve for ruxolitinib? As a follow up, you're starting this registrational program with TGFβR2 by PD-1 bispecific antibody. I'm kind of curious as you think about how large the study is, the delta that you need to show to have a positive study, how you come to the calculus given the kind of limited data that you have so far. Brian, thanks for the question. I'll take the first one, turn the second one over to Pablo.

And staving off this erosion curve for Brooks and as a follow up you're starting with Registrational program with.

TGF beta.

Kind of curious as you think about how large the study is the delta that you need to show.

Speaker #20: Are you looking at any potential combinations to move this forward with either the pipeline or in-licensing ? A product and staving off this erosion curve for for Rux and as a follow up , you know , you're starting this Registrational program with TGF beta .

A positive study how are you.

Come to the calculus, given the kind of limited data that you have so far.

Brian Thanks for the question I'll take the first one turn the second one over to Pablo right now our focus for XR is launching it for the Jakafi indications, we're not working on any combinations in development and we don't plan to right now I know that there was a there was a history there, but we're just focused on the once a day in Brazil.

Speaker #20: I'm kind of curious , as you think about how large the study is . The delta that you need to show to to have a positive study , how you come to the calculus , given the kind of limited data that you have so far .

<unk> some portion of that revenue stream getting a more convenient dosing regimen out as it relates to your second question I'll turn it over it actually Steven Stein, Yeah, Hi, Ryan. Thanks for the question. So its first line microsatellite stable colorectal cancer. The combination will be advancing as we alluded to at ESMO as with full Fox and Bev that's use of crop.

Speaker #5: Fran , thanks for the question . I'll take the first one turn . The second one over to Pablo . Right now , our focus for XR is launching it for the Jakafi indications we're not working on any combinations in development , and we don't plan to right now .

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

Speaker #5: I know that there was a there was a history there , but we're just focused on the once a day and preserving some portion of that revenue stream and getting a more convenient dosing regimen out as it relates to your second question , I'll turn it over to actually , Stephen Stein .

The board independent of Ras mutant fish wall type independent of left or right side of tumor they enabling safety work has already progressed well and will continue.

Speaker #11: Yeah . Hi . Thanks for the question . So it's first line microsatellite stable colorectal cancer . The combination will be advancing there .

Steven Stein: Yeah, hi Ren, thanks for the question. It's first line microsatellite stable colorectal cancer. The combination will be advancing there as we alluded to at ESMO, with FOLFOX and bev. That's used across the board, independent of RAS mutant versus wild type, independent of left or right sided tumor. The enabling safety work has already progressed well and will continue. There are benchmarks available both for progression free survival as well as overall survival. The primary endpoint, as we alluded to at ASH, will be PFS because OS takes a little longer to get there and the size we'll put up when we launch the study. You can estimate it's probably north of 500 and we'll be well powered to show the PFS advantage we want. Thanks.

<unk> benchmarks available both for progression free survival as well as overall survival. The primary endpoint as we alluded to at Ash will be PFS, because it always takes a little longer to get there and the size. We will put up when we launched the study, but you can estimate it's probably north of 500, and we will be well powered to show the PFS advantage we want.

Speaker #11: As we alluded to at SMO is with Folfox and Bev that's used across the board independent of Ras mutant versus wild type , independent of left or right sided tumor .

Speaker #11: The enabling safety work has already progressed well and will continue . There's benchmarks available both for progression free survival as well as overall survival .

<unk>.

Thanks, Ryan Thanks, Steven.

Thank you next question today is coming from Jessica Fye from JP Morgan. Your line is now live.

Speaker #11: The primary endpoint , as we alluded to at Ash , will be PFS because OS takes a little longer to get there , and the size will put up when we launch the study .

Hey, guys. Good morning, Thanks for taking my questions I had a couple more on 98 nine.

Speaker #11: But you can estimate , you know , it's probably north of 500 and we'll be well powered to show the PFS advantage . We want .

I guess for Pablo recognizing that we won't have frontline data for 99 by year end can you talk about what elements of these data in post jakafi patients in Jakafi suboptimal responders could make us confident that 99 could be successful in the frontline and I guess, specifically for that combo data.

Speaker #11: Thanks .

Speaker #5: Thanks , Ryan . Thanks , Stephen .

Hervé Hoppenot: Thanks, Ryan. Thanks, Stephen.

Speaker #2: Thank you . Next question today is coming from Jessica five from JP Morgan . Your line is now live .

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

Speaker #21: Hey guys . Good morning . Thanks for taking my questions . I had a couple more on 989 . So I guess for Pablo , recognizing that we won't have frontline data for 989 by year end , can you talk about what elements of these data in post patients and suboptimal responders could make us come away confident that 99 could be successful in the front line ?

Operator: Hey guys, good morning. Thanks for taking my questions. I had a couple more on 989, so I guess for Pablo, recognizing that we won't have frontline data for 989 by year end, can you talk about what elements of these data in post-JAKi patients and Jakafi suboptimal responders could make us come away confident that 989 could be successful in the front line? I guess specifically for that combo data set. I know it's smaller, but what are you going to be looking for as proof points that 989 is offering clear clinical benefit on top of Jakafi in the absence of a control arm? Is there a certain magnitude of change from baseline on those key measures that you think would exclude any natural variability in the endpoints over time had the patients just remained on their Jakafi monotherapy? I have a follow up.

I know, it's smaller but what are you going to be looking for as proof points. At 99 is offering clear clinical benefit on top of Jakafi in the absence of a control arm.

Is there like a certain magnitude of change from baseline on those key measures that you think would exclude any natural variability in the endpoints over time had the patients just remained on their jakafi mono therapy.

Speaker #21: And I guess specifically for that combo data set , I know it's smaller , but what are you going to be looking for as proof points that 989 is offering clear clinical benefit on top of jakafi in the absence of a control arm , is there like a certain magnitude of change from baseline on those key measures that you think would exclude any natural variability in the endpoints over time ?

And then I have a follow up.

Thanks, Jess so I.

I think that the element that like with any early development program or the stage development program I think looking at the totality of the emerging evidence is important so the first part here is obviously looking at the safety profile. We showed that in ETF earlier. This year, we will show it in MF before the end of this year and because of exquisitely targeted nature of 989.

Speaker #21: Had the patients just remained on their jakafi monotherapy ? And I have a follow up .

Speaker #6: Thanks , Jess . So I think that the elements look like with any early development program , early stage development program , I think looking at the totality of the emerging evidence is important .

Pablo Cagnoni: Thanks, Jess. I think that the element, like with any early development program or the stage development program, is looking at the totality of the emerging evidence. The first part here is obviously looking at the safety profile. We showed that in ET earlier this year. We'll show it in MF before the end of this year. Because of the exclusively targeted nature of 989, we think that the safety profile, the really excellent profile that we've shown so far, is a key element for the future development. The second part is obviously efficacy. The two components, as I mentioned earlier, are the classic clinical endpoints we need to see as monotherapy in patients who are resistant, intolerant, or ineligible for Jakafi. We need to see clear evidence of impact on clinical endpoints: spleen reduction, improvement in symptoms, anemia improvements, in addition to translational endpoints.

We think that the safety profile the the really excellent probably that we've shown so far is a key key element for the future development. So the second part is obviously efficacy.

Speaker #6: So the first part here is obviously looking at the safety profile . We showed that in ET earlier this year . We'll show it in MF before the end of this year .

Okay.

The two components as I mentioned earlier are obviously the classic clinical endpoints, we need to see as monotherapy in patients, who are resistant or intolerant or or or ineligible for jakafi, we need to see clear evidence of impact on clinical endpoint spleen reduction improvement in symptoms and email improvements and additions.

Speaker #6: And because of exquisitely targeted nature of 989 , we think that the safety profile , the really excellent profile that we've shown so far is a key , key element for the future development .

Speaker #6: So the second part is obviously efficacy . The two components , as I mentioned earlier , are obviously the classic clinical endpoints . We need to see as monotherapy in patients that are resistant , intolerant , are ineligible for jakafi .

Translational endpoints.

Now when you look at the AD on a cohort that we're going to show some data I think it's important to remember that those are the hardest patients to treat those are patients that did not respond to jakafi in an ideal way. Despite a minimum of 12 weeks of treatment and being eight weeks on a stable dose so any improvement on classic endpoints in those patients. We think is highly <unk>.

Speaker #6: We need to see clear evidence of impact on clinical endpoints , spleen reduction , improvement in symptoms , anemia improvements . In addition to endpoints .

Meaningful when you look at the what's.

Speaker #6: Now , when you look at the add on cohort that we're going to translational show some data . I think it's important to remember that those are the hardest patients to treat .

Pablo Cagnoni: When you look at the add-on cohort that we're going to show some data, I think it's important to remember that those are the hardest patients to treat. Those are patients that did not respond to Jakafi in an ideal way despite a minimum of 12 weeks of treatment and being eight weeks on a stable dose. Any improvement on classic endpoints in those patients we think is highly meaningful. When you look at what's available in second-line MF, the benchmarks are pretty low, as I mentioned earlier, between 9% and 20% for SVR35, for example. In our view, when you combine the monotherapy data in second line together with the ability to combine 989 with Jakafi, together with the safety profile, I think it's very easy to put a story together that increases our confidence in our ability to move 989 to the frontline setting as quickly as possible.

What's available in second line MF, the benchmarks are pretty low as I mentioned earlier between nine and 20% for US. We've got 35 for example, so in our view when you combine.

Speaker #6: Those are patients that did not respond to jakafi . In an ideal way . Despite a minimum of 12 weeks of treatment and being eight weeks on a stable dose .

The monotherapy data in second line together with the ability to combine 99 with Jakafi together with the safety profile.

Speaker #6: So any improvement on classic endpoints in those patients , we think is highly meaningful . When you look at the what's available in second line , MF , the benchmarks are pretty low .

I think it's very easy to put a story together that increases our confidence in our ability to move 99 to the frontline setting as quickly as possible. Obviously at some point in 2026, we'll provide an update on the treatment naive patients as I mentioned earlier and that sort of would be the definitive element of that story.

Thanks, Jeff.

Okay.

Got it a follow up.

Looking at <unk> 25 in addition to <unk> 35.

You incorporate SCR twenty-five data into your decision making.

Pablo Cagnoni: At some point in 2026, we'll provide an update on the treatment-naive patients, as I mentioned earlier, and that will be the definitive element of that story.

We are really to be honest with you. We report both 25 and 35 US it has been done and out of the trials in the past.

Hervé Hoppenot: Thanks. Jess.

Some of these patients have relatively short follow up we have patients and roll out a range of doses. As you know there is a dose escalation trials. So we think it's important to have directional data, where the spleen shrinkage is going but the key element here is as we are at 35 and make no mistake about that we report 25 as well as 35 years, but we really care about.

Operator: Mentioned looking at SVR25 in addition to SVR35. How do you incorporate SVR25 data into your decision making?

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

Thank you. Our final question today is coming from Eric handler from two of Securities. Your line is now live.

Hey, guys. Thank you so much for taking my question. Another one on 98 nine.

So when it comes to Iraq Humble you said the rationale to develop both in suboptimal responders as well as in drugs nave patients or do you see.

Alexis Smith: Thank you. Our final question today is coming from Kriptiv Arakanda from Truist Securities. Your line is now live.

It is a better strategy to focus on one versus the other but the longer time and taking me what's the FDA guidance for the endpoints now I know you said do you need to hear about that F. 35, N TSS 50, but would they be co primary end points.

Operator: Hey guys, thank you so much for taking my question. Another one on 989. When it comes to a rux combo, is there a rationale to develop both in suboptimal responders as well as in rux naive patients? Do you see it as a better strategy to focus on one versus the other for the longer term? Secondly, what's the FDA guidance for the endpoints? I know you said you need to show both SVR 35 and TSS 50. Would they be co-primary endpoints and do you have to hit on both? Thank you.

And do you have to hit on both thank you.

So let me take the second part of the question first look we will have discussions with FDA on the appropriate regulatory endpoints for what is a novel treatment paradigm for patients with MF, which we think 99 represents we we think it's going to be based on clinical endpoints predominantly what those specific clinical endpoints will be will discuss it with FDA.

We think theres an argument to be made about modifying some of what has been done previously in terms of co primaries for US you got 35 in TSS 50, but the impact on anemia. For example, we think could be very important and very interesting for F. D. A.

Pablo Cagnoni: Let me take the second part of the question first. Look, we'll have discussions with FDA on the appropriate regulatory endpoints for what is a novel treatment paradigm for patients with MF, which we think 989 represents. We think it's going to be based on clinical endpoints, predominantly what those specific clinical endpoints will be. We'll discuss it with FDA. We think there's an argument to be made about modifying some of what has been done previously in terms of co-primaries for SVR 35 and TSS 50. The impact on anemia, for example, we think could be very important and very interesting for FDA to contemplate in terms of what pivotal trials we will do in MF. Those decisions are in the process of being made and we'll update you over time, probably in early 2026.

To contemplate in terms of what pivotal trials, we will do in that math.

These decisions are in the process of being made and we'll update you over time, probably in early 'twenty 'twenty six but we intend to develop 99 to try to address the needs of all patients with MF that I'm you can call out positive that includes patients that are naive or patients that were treated with jakafi initially and did not respond or were intolerant.

And in those two contexts monotherapy and in combination with rux, slitting and potentially kind of have a role will give you more details over time as we disclose the data great. Thanks, Bob Paolo Thanks Krishna.

Pablo Cagnoni: We intend to develop 989 to try to address the needs of all patients with MF that are mutant CALR positive. That includes patients that are naive or patients that were treated with Jakafi initially and did not respond or were intolerant. In those two contexts, monotherapy and in combination with ruxolitinib potentially can have a role. We'll give you more details over time as we disclose this data.

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

Yeah.

Yeah.

Hervé Hoppenot: Great. Thanks, Pablo. Thanks, Kripa.

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