英賽德 (INCY) 2025 Q3 法說會逐字稿

Greetings, and welcome to the Incyte third-quarter 2025 earnings conference call webcast. (Operator Instructions) 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.

大家好，歡迎參加 Incyte 2025 年第三季財報電話會議網路直播。（操作說明）提醒各位，本次會議正在錄音。現在我很高興將電話交給副總裁兼投資人關係主管 Alexis Smith。請繼續，艾莉克絲。

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 Investor section of our website to find the press release, related financial tables, and slides that follow today's discussion. On today's call, I'm joined by Bill, Pablo, and Tom, who will deliver our prepared remarks. Steven, Dave, Matteo, and Mohamed will also be available for Q&A.

謝謝。早安，歡迎參加 Incyte 2025 年第三季財報電話會議。在開始之前，我鼓勵大家造訪我們網站的投資者關係部分，尋找新聞稿、相關財務表格以及今天討論的幻燈片。今天，比爾、帕布羅和湯姆將與我一起參加電話會議，他們將宣讀我們準備好的演講稿。Steven、Dave、Matteo 和 Mohamed 也將參與問答環節。

I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. I'll now hand the call over to Bill.

我想指出，我們將做出一些前瞻性聲明，這些聲明是基於我們目前的預期和信念。這些聲明存在一定的風險和不確定性，我們的實際結果可能與此有重大差異。我建議您查閱我們在提交給美國證券交易委員會的文件中討論的風險因素，以了解更多詳情。現在我將把電話交給比爾。

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.

謝謝你，Alexis，大家早安。上次通話中，我告訴過你，我將重新審視公司，重點是把核心業務、研發重點和成本基礎理順。這當然是一個持續的過程，而且目前正在順利進行並按計劃推進。就核心業務而言，我的評估增強了我對我們主要產品成長潛力的信心。

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 Hem-Onc business, Niktimvo and Monjuvi, namely, remain strong. Our job right now is to keep it that way and to identify effective ways to optimize the promotional strategies and investment for these products to drive future growth.

正如我們今天宣布的那樣，我們本季業績強勁，總收入達 13.7 億美元，產品銷售額達 11.5 億美元。與前一年相比，分別成長了 20% 和 19%。Jakafi、Opzelura 以及我們的血液腫瘤業務 Niktimvo 和 Monjuvi 的基本面依然強勁。我們現在的工作是保持這種狀態，並找出有效的方法來優化這些產品的推廣策略和投資，以推動未來的成長。

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 Niktimvo, which is helping identify patients across multiple lines of therapy.

Jakafi 第三季銷售額達到 7.91 億美元，成長 7%，需求年增 10%。三種適應症均實現了全面成長。在MF領域，Jakafi的使用率持續成長，儘管面臨競爭，我們仍保持著市場佔有率領先地位。GVHD 的成長勢頭依然強勁，這得益於我們與 Niktimvo 的投資組合策略，該策略有助於識別多線治療的患者。

MPV is our largest growth driver, fueled by compelling MAJIC-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.

MPV 是我們最大的成長動力，這得益於令人信服的 MAJIC-PV 數據，該數據顯示出令人印象深刻的無血栓存活率。基於這一發展勢頭，我們將 Jakafi 的全年業績預期上調至 30.5 億美元至 30.75 億美元。

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 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.

Opzelura 第三季成長迅猛，並持續為公司營收做出重大貢獻。銷售額達 1.88 億美元，較上年成長 35%。其中，淨銷售額為 1.44 億美元，來自美國，較上年成長 21%。此次成長是基於兩種適應症的強勁處方需求以及在三大藥品福利管理機構 (PBM) 更有利的處方集排名。

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-sterile 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 were well-positioned to take advantage of this market dynamic.

7 月，我們重組了 Opzelura 銷售團隊，將其分為兩個專門的銷售團隊，一個負責 AD，一個負責白斑，以確保執行和持續成長。隨著越來越多的患者停止使用外用皮質類固醇，品牌非無菌外用藥市場繼續以 20% 的速度成長。鑑於 Opzelura 在快速緩解瘙癢和清除皮膚病變方面的療效，我們廣泛的處方醫生群體和藥品目錄覆蓋範圍使我們能夠很好地利用這一市場動態。

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

在國際市場上，用於治療白斑症的 Opzelura 銷售額總計 4,400 萬美元，比去年增長了 117%。法國、西班牙、義大利和加拿大占我們銷售額和成長的 80% 以上，我們計劃在年底前向歐盟提交魯索替尼乳膏用於治療中度 AD 的申請，並預計在 2026 年下半年獲得批准。

Now in its third-quarter post-launch, Niktimvo continues to outperform expectations across all launch metrics. Sales in the third quarter totaled $46 million, an increase of 27% versus the second quarter. 90% of BMT centers have adopted Niktimvo, with all centers placing repeat orders year to date. Importantly, 80% of patients who started treatment in the first quarter of launch are still on therapy today. And we've captured 13% of the third line plus GVHD opportunity in just the first nine months on the market.

Niktimvo 上線第三季以來，在所有上線指標上都繼續超出預期。第三季銷售額達4,600萬美元，較第二季成長27%。 90%的BMT中心已採用Niktimvo系統，且所有中心今年迄今均有重複訂購紀錄。值得注意的是，在產品上市第一季開始接受治療的患者中，有 80% 至今仍在接受治療。光是上市九個月，我們就佔了三線治療及 GVHD 市場 13% 的份額。

In line with expectations, Niktimvo was 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 Niktimvo in combination with Ruxolitinib and steroids in earlier line settings. Our combination study with Jakafi is designed to enable a steroid-free regimen in GVHD, which could shift the standard of care.

正如預期的那樣，Niktimvo 主要用於第四線，並且在第三線的偏好和使用率也在不斷提高。來自骨髓移植中心的回饋是正面的，實際療效和安全性與臨床數據一樣令人印象深刻。最後，我們正在積極研究 Niktimvo 與 Ruxolitinib 和類固醇聯合用於早期治療。我們與 Jakafi 的聯合研究旨在實現 GVHD 的無類固醇治療方案，這可能會改變治療標準。

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.

我們在第一線治療中採用類固醇合併治療的研究有可能達到基準療效並達到類固醇減量。這種特許經營策略有可能大幅擴大我們的潛在市場，並鞏固我們在 GVHD 領域的領導地位。

Our broader hematology and oncology portfolio also performed well this quarter. Sales from Monjuvi in follicular lymphoma and (inaudible) 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.

本季度，我們更廣泛的血液學和腫瘤學產品組合也表現良好。Monjuvi 用於治療濾泡性淋巴瘤的銷售額以及（聽不清楚）均於今年推出，實現了強勁增長，並促使我們提高了業績預期。這些產品將逐步豐富我們的產品組合，並有望在未來幾年內共同實現可觀的銷售成長。

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.

明年我們將推出三款重要的新產品：Ruxolitinib XR、歐洲的 Opzelura AD 以及 HS 的 Povorcitinib。我已經對產品上市計劃進行了全面審查，並相信這些產品有潛力為 Incyte 的未來發展做出重大貢獻。從策略角度來看，Ruxolitinib XR 核准後可提供與 Jakafi 相同的治療效果，每日一次給藥方案更方便。

The stability data are on track to be submitted to the FDA before end of year with an anticipated launch in mid-2026. As it relates to Opzelura AD, as mentioned, we plan to submit our application in the EU with an anticipated launch next year. Assuming approval, Opzelura has the potential to contribute meaningfully to future sales in the EU [4] and Canada, and to overall growth given its clinical and economic value proposition.

穩定性數據預計在年底前就交給FDA，預計2026年中期上市。關於 Opzelura AD，正如前面提到的，我們計劃向歐盟提交申請，預計明年推出。假設獲得批准，Opzelura 有望對歐盟 [4] 和加拿大的未來銷售做出有意義的貢獻，並且鑑於其臨床和經濟價值，有望對整體成長做出貢獻。

With the moderate AD indication in Europe, we could potentially increase our international topical business by 2x to 3x over the next several years. And 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.

鑑於歐洲 AD 的適度適應症，我們未來幾年內國際外用藥業務有可能成長 2 到 3 倍。最後，Povorcitinib 可能是治療化膿性汗腺炎（HS）患者的首個口服選擇，化膿性汗腺炎可能是皮膚病學中最具挑戰性的疾病。這是一種多細胞因子疾病，涉及多種通路，因此治療更加複雜，結果也更加不穩定。像 Povorcitinib 這樣的治療方案，已經顯示出快速緩解疼痛和超過 50% 的皮膚清除率，將非常有市場。

We believe there's a substantial opportunity in HS, which is the first step for Povo, our ongoing developments in PN and vitiligo, will come into focus next year, and if positive, further strengthening 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 engagement, and medical education initiatives. We'll share more details in early 2026.

我們相信在化膿性汗腺炎 (HS) 領域存在著巨大的機遇，這是 Povo 的第一步。我們在結節性多發性硬化症 (PN) 和白斑症方面的持續發展將在明年成為焦點，如果結果積極，將進一步鞏固 Povo 在我們皮膚科產品組合中的地位。與 Opzelura 合作，我們可以為 HS、白斑症和 PN 患者提供外用和口服的治療方案。各項產品的上市活動均按計劃進行，包括銷售團隊的準備工作、與支付方的溝通以及醫學教育計劃。我們將在2026年初分享更多細節。

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 outsized 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.

轉向研發。我們正在進行的研發管線審查讓我們非常清楚地了解哪些高價值項目是未來成長的核心，並且具有最大的創造價值和超額回報的潛力。我們希望配置一個平衡的管道，既不被安全的、低價值的項目消耗，也不被不切實際的、不切實際的項目消耗。我們為推進關鍵專案製定了明確的啟動/停止標準。我們將對重點項目進行投資並承擔經過深思熟慮的風險，而不是將投資分散到眾多項目中。

In other words, fewer, smarter investments versus diffused spending will fund what matters and importantly, watch out for false positives and negatives. As it relates to our developing pipeline, the first call on capital is Hem-Onc. This is central identity of the company and an area where we have differentiated knowledge and capabilities and an asymmetrical advantage.

換句話說，與其分散支出，不如進行更少但更明智的投資，這樣才能為真正重要的事情提供資金；更重要的是，要警惕誤報和誤漏。就我們正在開發的研發管線而言，首要的資金需求是血液腫瘤學。這是公司的核心身份，也是我們擁有差異化知識和能力以及不對稱優勢的領域。

This includes targeted therapies for MPNs, including [mCLR617], our mCLR 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.

這包括針對 MPN 的標靶治療，包括 [mCLR617]、我們的 mCLR 雙特異性和發現項目。我們現在有機會推動 MPN 治療從 Jakafi 和 HU 等非特異性對症療法轉向 989 等標靶突變特異性療法。 989 和 617 的後續步驟將在今年稍後和明年公佈。

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.

就我們的實體瘤計畫而言，我們癌症策略的基石是新型生物通路、高發生且具有重大醫療需求但錯過了免疫腫瘤革命的癌症，以及可以與標準治療方案聯合用於一線治療的免疫療法和標靶療法。

As you know, we have three programs early development: KRASG12D for pancreatic cancer, TGFβR2×PD-1 bispecific for MSS CRC, 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 providing our data continue to be objectively competitive, and we can be early to market and defend our position long term.

如您所知，我們有三個早期開發項目：KRASG12D 用於胰臟癌，TGFβR2βPD-1 雙特異性抗體用於 MSS CRC，以及 CDK2 用於卵巢癌。在接下來的幾個月裡，我們將收集更多關於這些項目的數據，包括反應率、反應持續時間和安全性，特別是與標準治療相結合的情況。只要我們的數據持續保持客觀競爭力，我們就會毫不拖延地向前推進，搶佔市場先機，並長期捍衛我們的市場地位。

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.

現在，就我們的營運費用和整體成本結構而言，我們正在對整個業務進行審查，重點是確定優先事項和數據驅動的權衡決策。我們的目標是在控製成本的同時，不削減關鍵項目的資金，從而避免損害成長前景。我們將努力在財務紀律和長期策略投資之間取得適當的平衡，這可以透過控制低價值領域的成本來實現，從而釋放資金，用於再投資於高價值機會或提高利潤率。

Our framework for the 2026 budget and beyond will be based on the following. First, define and ring fence our strategic growth drivers. This means the new product launches that I touched, on as well as key R&D projects, which we have earmarked as non-negotiable fully funded programs. Once we protect the growth drivers, we're looking to control costs in areas that add less or minimal strategic value. From there, the savings we've identified and achieved will either be reallocated or banked. This will be a continuous process, not a one-and-done exercise, it's a mindset. As our business evolves, so will our resource allocation.

我們2026年及以後的預算架構將基於以下內容。首先，明確並劃定我們的策略成長驅動因素。這意味著我剛才提到的新產品發布以及我們已指定為不可協商的全額資助項目的關鍵研發項目。在保護好成長動力之後，我們將著手控制那些策略價值較低或幾乎沒有策略價值的領域的成本。接下來，我們發現並實現的節省金額要么重新分配，要么存入銀行。這將是一個持續的過程，而不是一蹴而就的，這是一種思考方式。隨著業務的發展，我們的資源分配也會隨之改變。

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.

最後，是業務拓展。業務拓展需要強大的策略領導、高效率以及快速篩選機會和決策的框架，而這需要一支技術嫻熟的搜尋和評估團隊以及深厚的人脈網絡。要想取得成功，我們需要在重點領域內有效運作。

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.

因此，Dave Gardner 於 9 月加入 Incyte 擔任首席策略官，他的首要任務之一就是建立這種能力。他將在我們長期成長策略的發展中發揮核心作用，並確保外部業務發展機會和內部投資組合決策在策略上合理且在財務上具有吸引力。我們將於明年初公佈有關戰略評估的更多細節。

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

現在我想把電話交給巴布羅。

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.

謝謝你，比爾，大家早安。如投影片 14 所示，我們的研發管線具有策略重點，目前正在開發眾多具有重大影響力的項目。在過去的幾個月裡，我們進行了全面的專案儲備審查，以確保我們將精力和資源集中在對公司未來發展至關重要的專案上。正如比爾所提到的那樣，這個過程遵循一套明確的通過/不通過標準，使我們能夠就推進哪些專案做出策略決策。

As a result, we have decided to pause or stop several preclinical and early clinical stage programs, including INCA34460, our anti-CD122 program; INCB57643, our BET inhibitor program, and the development of Povorcitinib in chronic spontaneous urticaria. By continuing to streamline our pipeline, we will be able to accelerate and prioritize the programs with the greatest potential impact to patients and to drive future growth.

因此，我們決定暫停或停止幾個臨床前和早期臨床階段的項目，包括我們的抗 CD122 項目 INCA34460；我們的 BET 抑制劑項目 INCB57643，以及 Povorcitinib 在慢性自發性蕁麻疹的開發。透過不斷精簡我們的研發管線，我們將能夠加速並優先考慮那些對患者影響最大、能夠推動未來成長的項目。

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 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.

現在我想重點介紹本季度的一些重要進展，特別是Povorcitinib和我們實體瘤產品線的最新進展。我也會討論我們突變 CALR 抗體計畫在 2025 年剩餘時間內的預期成果。上個月，我們在歐洲皮膚病和性病學會大會上公佈了 Povorcitinib 在化膿性汗腺炎中的長期數據，進一步強化了 Povorcitinib 的差異化特性。

The 24-week data demonstrated deep and sustained improvements across key clinical endpoints, including HiSCR50, 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. (inaudible) experience in the management of HS emphasize that their primary focus when they treat patients with HS is on two elements, help patients feel better by addressing the pain related to HS and to effectively control flares.

24 週的數據顯示，關鍵臨床終點指標均有顯著且持續的改善，包括 HiSCR50、75、90 和 100，引流隧道的消失，以及病情發作的有效減少。Povorcitinib 也顯示出快速且顯著的皮膚疼痛減輕，到第 24 週時，62% 至 70% 的患者報告疼痛輕微或無疼痛。 （聽不清楚）在化膿性汗腺炎 (HS) 管理方面的經驗強調，他們在治療 HS 患者時主要關注兩個方面：透過解決與 HS 相關的疼痛來幫助患者感覺更好，並有效控制病情發作。

The data percentage show that Povorcitinib provides rapid and sustained pain relief and reduces the frequency of flares. This 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.

數據顯示，Povorcitinib 能快速且持續地緩解疼痛，並減少疼痛發作的頻率。這項積極的 3 期試驗結果表明，Povorcitinib 有潛力滿足超過 30 萬名患有中度至重度 HS 患者的重大醫療需求，為這一服務不足的患者群體提供了一種新型、有效且方便的口服治療選擇。

Moving to slide 16 and the near-term opportunities for Povorcitinib. As you know, HS is the most advanced programs, and we're on track with our regulatory submission at the end of the year in the EU and early 2026 in the US, with potential approvals and launches in late 2026, early 2027. In addition to HS, we're starting Povorcitinib in three other indications, underscoring its potential to become a major growth driver for the company.

接下來看第 16 張投影片，了解 Povorcitinib 的近期機會。如您所知，HS 是最先進的項目，我們正按計劃推進監管申報工作，預計將於今年年底在歐盟提交，並於 2026 年初在美國提交，預計在 2026 年底或 2027 年初獲得批准並上市。除了 HS 之外，我們還將 Povorcitinib 用於其他三種適應症，這凸顯了它有可能成為公司主要成長動力。

Povorcitinib is being evaluated in Phase 3 programs in vitiligo and prurigo nodularis as well as a Phase 2 proof-of-concept study in asthma. We anticipate pivotal data readouts for vitiligo and PN in 2026 with a goal of potential initial regulatory approvals in 2027, 2028.

Povorcitinib 正在白斑症和結節性癢疹的 3 期臨床試驗中進行評估，同時也在氣喘的 2 期概念驗證研究中進行評估。我們預計在 2026 年將公佈白斑症和 PN 的關鍵數據，目標是在 2027 年、2028 年獲得初步監管批准。

Next, I would like to highlight two recent updates from our solid tumor portfolio, beginning with our TGFßR2xPD-1 bispecific antibody program. This month, at the European Society of Medical Oncology Annual Meeting we presented initial Phase 1 data for INCA33890, as I'll refer to moving forward, 890, our first-in-class TGFßR2xPD-1 bispecific antibody in patients with solid tumors.

接下來，我想重點介紹我們實體瘤產品組合的兩個最新進展，首先是我們的 TGFÃR2xPD-1 雙特異性抗體計畫。本月，在歐洲腫瘤內科學會年會上，我們公佈了INCA33890（以下簡稱890）的初步1期數據，INCA33890是我們首創的TGFÃR2xPD-1雙特異性抗體，用於治療實體瘤患者。

This is an inside discover compound and one that is truly differentiated from other TGF-beta and PD-1 approaches. The Phase 1 trial evaluated 890 in solid tumors with a focus on microsatellite stable or MSS colorectal cancer patients. 890 demonstrated durable single-agent anti-tumor activity and a manageable safety profile in heavily pretreated MSS colorectal cancer patients, a population with limited treatment options and where anti-PD-1, PD-L1 antibodies have historically produced response rates from 0% to 2%.

這是一個內部發現的化合物，它與其他 TGF-β 和 PD-1 療法真正不同。這項 I 期臨床試驗評估了 890 在實體腫瘤中的療效，重點是微衛星穩定型 (MSS) 大腸直腸癌患者。 890 在先前接受過大量治療的 MSS 大腸直腸癌患者中展現出持久的單藥抗腫瘤活性和可控的安全性。這類患者的治療選擇有限，且先前抗 PD-1 和 PD-L1 抗體的緩解率僅為 0% 至 2%。

In patients with MSS colorectal, 890 achieved an overall response rate of 15% and most notably, responses were observed in patients with and without liver metastases. The majority of treatment-related adverse events were low grade with no dose-limiting toxicities reported. We also completed dose escalation of 890 in combinations of four cohorts. FOLFOX for bevacizumab, FOLFIRI plus bevacizumab, bevacizumab and cetuximab.

在 MSS 大腸直腸癌患者中，890 例患者的整體緩解率為 15%，尤其值得注意的是，無論患者是否出現肝轉移，均觀察到了緩解。大多數與治療相關的不良事件均為低級別，未報告劑量限制性毒性。我們也完成了 890 例患者在四個隊列組合中的劑量遞增試驗。FOLFOX 用於貝伐單抗、FOLFIRI 加貝伐單抗、貝伐單抗和西妥昔單抗。

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

在所有合併用藥組中均未觀察到疊加毒性的證據，劑量擴展仍在進行中。這些初步結果為將 890 推進到註冊程序提供了強有力的理由。我們計劃於 2026 年啟動一項關鍵的 3 期試驗，評估 890 與貝伐單抗聯合標準治療化療用於一線 MSS 結直腸癌患者的療效。

Turning to our KRASG12D program on slide 18. We recently presented encouraging clinical data from the Phase 1 trial of INCB161734, 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-limited toxicities observed and predominantly Grade 1 treatment-related adverse events.

請翻到第 18 頁投影片，查看我們的 KRASG12D 程式。我們最近公佈了 INCB161734（或我以後簡稱的 734）在 1 期試驗中令人鼓舞的臨床數據，該試驗針對的是攜帶 KRASG12D 突變的晚期或轉移性實體瘤患者，這些患者曾接受過大量預處理，其中包括胰腺導管腺癌等。結果顯示安全性良好，未觀察到劑量限制性毒性，且主要為 1 級治療相關不良事件。

Importantly, in pancreatic adenocarcinoma patients, 734 showed promising antitumor activity with an objective response rate of 34%, disease control rate of 86% of the dose of 1,200 milligrams. These results are particularly notable given that only eight of the patients were treated in the second-line setting.

重要的是，在胰臟腺癌患者中，734 顯示出良好的抗腫瘤活性，客觀緩解率為 34%，疾病控制率為 86%（劑量為 1,200 毫克）。考慮到只有 8 名患者接受了二線治療，這些結果尤其值得關注。

To summarize, both our TGFβR2xPD-1 and our KRASG12D program represents significant opportunities to address large patient populations with high medical need, specifically MSS colorectal cancer and pancreatic ductal adenocarcinoma. As Bill noted, our strategy in both cancers will be to win and frontline in combination with standard of care.

總而言之，我們的 TGFβR2xPD-1 和 KRASG12D 計畫都代表著為解決醫療需求高的龐大患者群體（特別是 MSS 結直腸癌和胰腺導管腺癌）提供重要的機會。正如比爾所指出的，我們針對這兩種癌症的策略都是爭取勝利，並結合標準治療方案進行第一線治療。

For 890, we have demonstrated durable single-agent activity in heavily pretreated MSS colorectal cancer patients, including those with liver metastases, and a favorable safety profile and combinability for first-line standard of care regimens. As previously mentioned, we're planning to initiate a Phase 3 study in first-line MSS colorectal in 2026. Similarly, 734 has shown promising anti-tumor activity and manageable safety profile in advanced solid tumors with particularly encouraging results in PDAC. We'll share more updates on this program next year.

對於 890，我們已經證明其在接受過大量預處理的 MSS 結直腸癌患者（包括肝轉移患者）中具有持久的單藥活性，並且具有良好的安全性和與一線標準治療方案聯合使用的可行性。如前所述，我們計劃於 2026 年啟動第一線 MSS 大腸直腸癌的 3 期研究。同樣，734 在晚期實體瘤中顯示出良好的抗腫瘤活性和可控的安全性，在 PDAC 中尤其取得了令人鼓舞的結果。明年我們將分享更多關於該專案的最新進展。

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 towards the milestones we established at the beginning of the year. As we look at the remainder of the year, we plan to share data for the first time on 989, our mutant CALR antibody in patients with myelofibrosis.

現在就來看第 20 張投影片。 2025 年是 Incyte 的關鍵一年，亮點包括推出多個新產品、關鍵試驗結果公佈、啟動 3 期研究以及概念驗證結果。這些成就反映了我們朝著年初設定的目標取得了堅實的進展。展望今年剩餘時間，我們計劃首次分享 989 的數據，989 是我們的突變 CALR 抗體，用於治療骨髓纖維化患者。

We are evaluating 989 in a broad population of patients with MF. There are three actively enrolling cohorts. First, intermediate to high-risk patients who are intolerant, ineligible, or resistant to a JAK inhibitor. This cohort is evaluating 989 as a monotherapy. Second, intermediate to high-risk patients who are on Ruxolitinib, but experienced a suboptimal spleen response after these 12 weeks of treatment. In this cohort, we are evaluating adding 989 to Ruxolitinib.

我們正在對 989 名患有 MF 的廣大患者進行評估。目前有三個正在招募學員的隊列。首先，對於不耐受、不符合條件或對 JAK 抑制劑產生抗藥性的中高風險患者。研究團隊正在評估 989 作為單藥療法的療效。第二，中高風險患者正在接受魯索替尼治療，但在 12 週的治療後脾臟反應不理想。在本組患者中，我們正在評估將 989 加入魯索替尼治療方案中。

And finally, we're enrolling patients with intermediate to high-risk treatment-naive MF in a cohort evaluating 989 compared to a combination of 989 and Ruxolitinib. This will allow us to see how 989 performs as a monotherapy and in combination with Ruxolitinib in treatment-naive patients. Our update later this year will include early data from the first two cohorts.

最後，我們正在招募中高風險未接受過治療的 MF 患者，組成一個隊列，評估 989 與 989 和魯索替尼合併用藥的療效。這將使我們能夠了解 989 作為單藥療法以及與魯索替尼聯合療法在初治患者中的療效。今年稍後我們將發布更新報告，其中包含前兩批受試者的早期數據。

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 on at least 15 suboptimal responders to Ruxolitinib. More than half of these patients will have a minimum of 24 weeks of follow up.

對於單藥治療組，我們計劃分享約 50 名患者的數據，其中約三分之二的患者將接受超過 24 週的追蹤。此外，還將展示聯合治療組中至少 15 名對魯索替尼反應不佳的患者的數據。超過一半的患者將接受至少 24 週的追蹤。

Importantly, the update will include response data used in traditional endpoints as VR25, SBR35, TSS50, and anemia and molecular endpoints like (inaudible) 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 thrombocytemia as a follow up to the encouraging results presented earlier this year.

重要的是，此次更新將包括傳統終點（如 VR25、SBR35、TSS50 和貧血）和分子終點（如（聽不清楚）血液、週邊血單核細胞中的 CD34 陽性突變 CALR 細胞和骨髓中的突變 CALR 陽性巨核細胞）中使用的反應數據。此外，我們將提供 989 名接受治療的原發性血小板增多症患者的最新情況，作為對今年早些時候公佈的令人鼓舞的結果的後續報道。

As you'll recall from EHA presentation, 989 demonstrated the rapid and sustained normalization of platelet counts and was well tolerated with only one patient discontinuing due to an adverse event. We look forward to sharing updates on the remaining 2025 milestones and to provide further visibility into our 2026 catalyst as we continue to advance our pipeline.

正如您在 EHA 會議上所看到的，989 顯示出血小板計數的快速和持續正常化，並且耐受性良好，只有一名患者因不良事件而停止治療。我們期待與大家分享 2025 年剩餘里程碑的最新進展，並隨著我們繼續推進產品線，進一步闡明我們 2026 年的催化劑。

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

接下來，我將把發言權交給湯姆，讓他報告本季的財務狀況。

Thanks, Pablo. As Bill mentioned earlier, our total revenues and product revenues were $1.37 billion and $1.15 billion, respectively, increasing 20% and 19% from the prior year. Our total GAAP R&D expenses were $507 million in the third quarter. Excluding one-time expenses in the prior year, R&D expenses increased 7% year over year, driven by continued investment in our late-stage development assets.

謝謝你，帕布羅。正如比爾先前所提到的，我們的總收入和產品收入分別為 13.7 億美元和 11.5 億美元，比前一年分別成長了 20% 和 19%。第三季度，我們以美國通用會計準則計算的研發費用總額為 5.07 億美元。剔除上一年度的一次性支出，研發支出年增 7%，這主要得益於我們對後期開發資產的持續投資。

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.

移至銷售、一般及行政管理部門。第三季 GAAP SG&A 總支出為 3.29 億美元，較去年同期成長 6%，主要原因是為支持產品上市而進行的國際行銷活動。第三季持續經營支出較去年同期成長 8%，而同期持續營收年增 18%，導致經營槓桿和利潤率持續上升。

Based on the growth of our product portfolio, we raised 2025 full-year net product revenue guidance to $4.23 billion to $4.32 billion. We maintain our prior OpEx guidance of $3.25 billion to $3.31 billion, which reflects combined R&D and SG&A GAAP expenses. I now turn the call over to Bill.

基於我們產品組合的成長，我們將 2025 年全年淨產品收入預期上調至 42.3 億美元至 43.2 億美元。我們維持先前對營運支出的預期，即 32.5 億美元至 33.1 億美元，這反映了研發和銷售、管理及行政費用的綜合 GAAP 支出。現在我把電話轉給比爾。

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

謝謝你，湯姆。我們的發言稿到此結束。請開放問答環節。

(Operator Instructions) Tazeen Ahmed, Bank of America.

（操作員說明）美國銀行 Tazeen Ahmed。

Thanks for taking my question. I wanted to focus on the upcoming mCALR data, you've given us a good preview of how many patients worth of data to expect. I think most people are going to be focused on the monotherapy arm. How important is that going to be for people to believe that you have convinced efficacy as it stands alone because there could potentially be the view that it could be synergistic with when added to Jakafi.

謝謝您回答我的問題。我想專注於即將發布的 mCALR 數據，您已經讓我們很好地了解了將會有多少患者的數據。我認為大多數人都會關注單藥治療組。對人們來說，相信該產品本身俱有令人信服的功效有多重要？因為人們可能會認為，當它與 Jakafi 結合使用時，可能會產生協同作用。

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 in combination with Jakafi.

所以，您能否為我們設定一個標準，您認為達到怎樣的療效水平才足以令人信服，從而推動其發展，即使是與 Jakafi 聯合使用。

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

謝謝你，塔津。我把它交給巴勃羅。

Thank you for the question. So 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, 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.

謝謝你的提問。所以我認為，關於我們的突變 CALR 抗體計劃，有幾件事需要記住。首先，這是首個針對骨髓增生性腫瘤患者的標靶療法。我們在這裡討論的是 MF，廣義上講，對於骨髓增生性腫瘤，包括 MF 和 ET，這是第一個真正意義上的標靶治療，與過去非特異性治療（包括魯索替尼）不同，後者主要改善症狀，對疾病改變幾乎沒有影響。

Now you're asking specifically about the update at ASH, I think it's very important for us to demonstrate that there is single-agent activity with 989. That's why the update will include a large number of patients, as I mentioned, 50 patients with somewhat significant follow up to really prove convincingly that 989 has single-agent activity.

現在你具體問到了 ASH 的最新進展，我認為對我們來說，證明 989 存在單一代理活動非常重要。因此，正如我所提到的，此次更新將包括大量患者，50 名患者，並進行相當程度的隨訪，以真正令人信服地證明 989 具有單藥活性。

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

重點不僅在於我們認為至關重要的臨床終點（脾臟縮小、症狀改善、貧血），還在於一系列轉化終點（我們認為這些終點對於證實我們的觀點，即這種新藥具有潛在的疾病改善作用，非常重要）。因此，就JAK抑制劑對先前接受過治療的患者的療效基準而言，我認為我們最近最好的基準是莫美替尼。

As you know, momelotinib has an SVR35 or between 7% and 22% in different studies, with the TSS50 improvements in the 25% to 26%. Those are some reasonable benchmarks in the second-line setting to look at, but it's very important for us to confirm the single-agent activity of 989 in MF patients, Tazeen.

如您所知，在不同的研究中，momelotinib 的 SVR35 為 7% 至 22%，TSS50 改善率為 25% 至 26%。Tazeen，這些是二線治療中一些合理的基準，但對我們來說，確認989在MF患者中的單藥活性非常重要。

Andrew Berens, Leerink Partners.

安德魯貝倫斯，Leerink Partners。

Congratulations on the execution during the quarter. I was wondering if you could give some more color on the decision to terminate the Povo program in CSU following your announcement in April that Phase 2 is successful. Are we going to see the data at a medical meeting as you've previously guided?

恭喜你們本季業績出色。我想請您詳細說明一下，在您於 4 月宣布第二階段取得成功之後，為何決定終止科羅拉多州立大學的 Povo 計畫。我們是否會像您之前指導的那樣，在醫學會議上看到這些數據？

Yeah, Andy, I'll start off and then turn it over to Pablo. As it relates to Povo 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. And the factors that went into the decision included differentiation, competitive intensity, timing to market, and market potential among other factors.

好的，安迪，我先開始，然後交給帕布羅。就科羅拉多州立大學的 Povo 計畫而言，對我們來說，關鍵在於優先事項。當我們優先考慮回報率較高的項目時，就必須這樣做。這是一個不錯的第二階段項目，但我們有更好的第三階段項目。做出這項決定的因素包括差異化、競爭強度、上市時機和市場潛力等。

And Pablo, you want to just comment on the release of the data?

巴勃羅，你只想對數據發布發表一些評論嗎？

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, 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 a lot of priorities to focus on.

當然。我們還沒有和調查人員決定是否公佈數據，但安迪，我們幾乎肯定會在未來的某個會議上公佈這些數據。我還要補充比爾的觀點，除了這些因素之外，科羅拉多州立大學的監管門檻（我們與FDA討論過）以及科羅拉多州立大學潛在關鍵項目的要求都非常苛刻，我們決定有很多優先事項需要關注。

Okay. Thanks. And then if I could, just a question on the PD-1 TGF beta. I was at ESMO. I thought it was really encouraging and you guys are advancing into Phase 3. Are we going to see combination data before you make that decision to advance? Is there like -- I think there's like a run-in looks like on the clinicaltrials.gov?

好的。謝謝。如果可以的話，我想問一個關於 PD-1 TGF-β 的問題。我當時在ESMO大會上。我覺得這非常令人鼓舞，你們已經進入第三階段了。在您決定是否要推進之前，我們會看到合併後的數據嗎？好像－我覺得clinicaltrials.gov網站好像有個類似的活動？

So the decision to advance the TGFßR2×PD-1 programming combination with chemotherapy first-line in colorectal is 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 those two things are happening in parallel. We think speed is of the essence here in executing this Phase 3 trial, so we're advancing this rapidly, and we'll generate the data and release it at some point.

因此，決定將 TGF-β2-PD-1 編程與化療第一線合併用於大腸直腸癌治療。我們正朝著這個方向前進。同時，我們正在利用這種組合生成數據，我們將在明年某個時候發布這些數據，安迪。但這兩件事是同時發生的。我們認為速度是執行這項 3 期試驗的關鍵，因此我們正在快速推進，我們將在某個時候產生數據並發布。

Stephen Willey, Stifel.

Stephen Willey，Stifel。

Just two quick ones for me. So on 989, I was just wondering if you could give a little bit of color around what we should expect to see within the abstract publication next week, just relative to the presentation itself. And then just a quick one on Niktimvo. Curious how you're thinking about Sanofi's failed frontline trial with Rezurock steroids in terms of read-through to the ongoing Phase 3 trial with Niktimvo, and just whether you think that might say anything about the biology of the disease being different in a newly diagnosed patient.

我只需要回答兩個問題。所以，關於989，我只是想問一下，您能否就下週的摘要出版物中我們應該看到的內容，就其與演講本身的關係，做一些說明。然後簡單提一下 Niktimvo。我很好奇您如何看待賽諾菲 Rezurock 類固醇一線試驗的失敗，以及它對正在進行的 Niktimvo 3 期試驗的影響，還有您是否認為這可能說明新確診患者的疾病生物學特性有所不同。

I'm going to turn the second question about Niktimvo over to Steven Stein, and then Pablo will grab the first question.

我將把關於 Niktimvo 的第二個問題交給 Steven Stein，然後 Pablo 將回答第一個問題。

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

是的，史蒂夫，謝謝你的提問。對於第一線移植物抗宿主疾病合併類固醇治療而言，如何衡量主要終點和無事件存活期確實存在一些爭議。而且，對於你所說的「事件」還有一些細微差別。因此，我們認為我們的定義是可靠的，並且能夠充分展現我們戰勝類固醇所需的差異。正如比爾在事先準備好的演講稿中所說，也要展示醫生們非常希望看到的，那就是盡快停止使用類固醇以避免副作用。

But you're right in the sense that it's -- it shows the difficulty in this arena of beating 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.

但你說的沒錯，這確實表明了在對抗類固醇這個領域中的難度，類固醇雖然有效，但我們真的認為關鍵在於終點的定義，而我們的終點是可靠的，滿足了我們項目的需求，我們對此充滿信心。

Thanks, Steve. And the only other thing I would add, Steve, here, is we -- fortunately, with Niktimvo -- have two shots on goal. We have a 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 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 Niktimvo fairly significantly.

謝謝你，史蒂夫。史蒂夫，我唯一要補充的是，幸運的是，有了尼克蒂姆沃，我們有兩次射門機會。我們正在進行一項類固醇與 Jakafi 合併用藥的研究。顯然，這些都是經過權衡的風險。與 Jakafi 合併用藥的研究結果呈陽性，目標族群翻了一番，且治療方案不含類固醇。顯然，我們希望這兩個計畫都能成功，如果成功，可能會對尼克提姆沃的發展軌跡產生相當大的影響。

Pablo, you want to address the first question?

帕布羅，你想回答第一個問題嗎？

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 patience. It's going to have longer follow up. So 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.

當然。我認為，對於 989 號項目，我們應該專注於年底前的演示。這是較晚的數據版本。它會更有耐心。後續追蹤時間會更長。我知道摘要將會發布，但我請您等待我們在年底前提供的更新，並專注於該更新，因為它內容更豐富，尤其是後續研究的時間更長。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

Congrats on the quarter, and thanks for taking the questions. Can you describe the rationale behind terminating the BET inhibitor program with that mostly related to your strategic focus on targeted therapies like mCALR 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 mCALR into registrational studies?

恭喜你本季取得好成績，謝謝你回答問題。您能否描述一下終止 BET 抑制劑專案的理由，主要與貴公司將策略重點放在標靶治療（如 mCALR 和骨髓纖維化）有關？作為對上述問題的進一步探討，既然 BET 抑制劑已按計劃開始註冊研究，那麼 mCALR 多久才能進入註冊研究階段？

I'll take the first part and then turn it over to Pablo. As it relates to the BET inhibitor, the risk-benefit calculus, as you know, for BET inhibitors right now is complex, differentiating class-wide risks from molecule-specific ones is challenging. And so in general, we're prioritizing programs with a higher PTRS 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.

我先負責第一部分，然後交給巴布羅。就 BET 抑制劑而言，如您所知，目前 BET 抑制劑的風險效益計算很複雜，區分此類藥物的風險和分子特異性風險是一項挑戰。因此，總的來說，我們會優先考慮 PTRS 值較高且市場推廣路徑更清晰的項目。這就是我們停止 BET 抑制劑計劃的根本原因，接下來就讓 Pablo 來進一步評論。

So I don't have anything to add into 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 to start, and that should start at some point in the first half of the year.

因此，對於終止該專案的原因，我沒有什麼要補充的。傑伊，就 CALR 抗體計畫而言，目標是在 2026 年啟動一項或多項關鍵性試驗。正如我們在 ET 的 EHA 更新中提到的那樣，ET 很可能是第一個開始的關鍵性試驗，並且應該會在今年上半年的某個時候開始。

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 terminus of the BET program, in no way, reduces ambition in MPNs.

同時，我們正在與監管機構進行互動，並繼續審查數據，以便確定合適的試驗和實施骨髓纖維化患者 3 期試驗的時間，這些試驗很可能在 2026 年下半年的某個時候開始。我想強調的一點是，BET 計畫的結束絕對不會降低 MPN 的雄心壯志。

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.

正如我今年早些時候提到的，我們的目標是在本十年末為每位患有骨髓增生性腫瘤的患者找到解決方案。我們正在建立一系列針對性療法以滿足這一需求，並且我們打算繼續推進這些計畫。

James Shin, Deutsche Bank.

James Shin，德意志銀行。

First one is for Pablo. Pablo, appreciate 989 as a targeted therapy for MPNs. But can you say whether or not we should expect SCR, TSS, and anemia burden, at least on the kinetics front, to look similar to Rux. And follow up for Bill, Jakafi's (inaudible) 1 and 2 set a high bar for frontline myelofibrosis. So from a timing, financial, and regulatory perspective, can you share Incyte's progress on gaining certainty for 989 frontline MS (inaudible). And will that development path align with Jakafi's LOE?

第一封是給巴布羅的。Pablo，請欣賞 989 作為 MPN 的標靶療法。但是，您能否說明我們是否應該預期 SCR、TSS 和貧血負擔，至少在動力學方面，與 Rux 相似？比爾的後續研究顯示，Jakafi 的（聽不清楚）1 和 2 為第一線骨髓纖維化設定了很高的標準。那麼從時間、財務和監管的角度來看，您能否分享一下 Incyte 在獲得 989 一線 MS 藥物的確定性方面取得的進展（聽不清楚）。這種發展路徑是否符合 Jakafi 的 LOE？

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

是的。好的，帕布羅，你可以回答問題的第一部分。

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

直接回答您的問題對我們來說非常重要，證明 989 對骨髓纖維化的臨床終點有影響對我們來說非常重要。因此，本次報告將包括 SVR25、SVR35、TSS50 效應以及對貧血的影響。我們意識到，這些因素的結合對於該專案至關重要，即在 MF 中批准終點，並在這些方面證明療效。所以這些內容將包含在我們年底前提供的更新中。讓我把話轉給比爾。

Yeah. And as it relates to both 989 in ET and MF, and how we think about the business post 2029, filling a revenue gap is not what 989 does. What 989 does is built a long duration revenue and cash flow stream well into the next decade. So we don't see the end of the road. And here's how I think about second line, first line, and Pablo commented on this.

是的。就 ET 和 MF 中的 989 而言，以及我們對 2029 年以後業務的思考而言，填補收入缺口並不是 989 的作用。989 的做法是建立一個能夠持續到下一個十年的長期收入和現金流。所以我們看不到路的盡頭。這就是我對第二行、第一行的看法，Pablo 也對此發表了評論。

There are targeted treatments available in many other cancers, 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 the standard of care. It's the most widely used cytoreductive agent in ET, but it achieves only a partial response, not a complete response in most patients.

許多其他癌症都有針對性的治療方法，但MPN卻沒有。因此，對於血液科醫師來說，首個標靶療法具有內在的吸引力。而對 ET 來說，羥基脲是標準治療方法。它是ET中最廣泛使用的細胞減滅劑，但對大多數患者來說，它只能達到部分緩解，而無法達到完全緩解。

And there's three consequences to that. The first one is residual symptoms, not as significant as it is in MF, but residual symptoms. The second consequence is residual thrombotic risk. And the third consequence is residual transformation risk. 989 solves the problems that HU created and even a second-line single-agent study or with those data, I expect that 989 will reshape the use of hydroxyurea where patients transition therapy rapidly because 989 is targeting disease-causing cells, it's better tolerated.

這會造成三個後果。第一種是後遺症，雖然不像 MF 那麼嚴重，但確實是後遺症。第二個後果是殘餘血栓風險。第三個後果是殘留轉化風險。 989解決了羥基脲（HU）帶來的問題，即使是二線單藥治療研究或基於這些數據，我也預期989將重塑羥基脲的使用方式，使患者能夠快速過渡到其他治療方案，因為989靶向致病細胞，耐受性更好。

For example, HUs has got seven warnings and precautions, and it's easier to dose. The market for ET is about $5 billion, ET mCALR patients. Roughly half of them are resistant or intolerant to therapy. And so I think there's a clear glide path to growth in ET with the first study.

例如，HUs 有七項警告和注意事項，而且更容易控制劑量。ET 的市場規模約為 50 億美元，ET mCALR 患者。其中約有一半人對治療有抗藥性或不耐受性。因此，我認為第一項研究為ET的成長指明了清晰的軌道。

And then as it relates to MF, it's of course, a completely different type of MPN. The risk of transformation to leukemia is real. It's more aggressive, it's more symptomatic. As effective as Jakafi is, as you know, the SVR35 is between 30% and 40%, right? Symptoms are in the mid-50s.

至於 MF，它當然是完全不同的 MPN 類型。存在發展為白血病的風險。它更具侵襲性，症狀更明顯。如您所知，Jakafi 的療效雖然很好，但其 SVR35 值在 30% 到 40% 之間，對嗎？症狀出現在50多歲。

Everybody on Jakafi progresses. And so even in a second-line setting, there is going to be just like an ET, a move to either [add] 989 -- we'll have to, of course, produce that data -- or use at 989 after Jakafi. And I think that the opportunity in both MF and ET is fairly significant. And what we're looking to is build the business well into the next decade. If we start the studies in the middle of '26, give or take, we should be getting out some time in that '29, '30 period.

在Jakafi平台上，每個人都能進步。因此，即使在第二線設定中，也會像 ET 一樣，要么[添加] 989——當然，我們必須生成該數據——要么在 Jakafi 之後使用 989。我認為MF和ET領域都蘊藏著相當大的機會。我們希望在未來十年將業務發展壯大。如果我們在 2026 年中開始這項研究，那麼我們應該會在 2029 年或 2030 年期間完成。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Thanks for taking my questions. You've highlighted [VAF] as an important part of the mCALR story in terms of the MPN story in terms of the drug being functional cure. And 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.

謝謝您回答我的問題。您強調了 [VAF] 是 mCALR 故事中的一個重要部分，因為它與 MPN 的故事以及藥物的功能性治癒有關。請您提醒我們您希望在 VAF 減少方面看到什麼，並告知我們您對 VAF 與臨床結果之間最終相關性的理解程度。

And just a second question here, Bill, on your -- 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.

比爾，我還有一個問題，關於你——你強調了你對控制營運費用和精簡公司流程的重視。您如何看待公司未來幾年以及透過 Jakafi LOE 實現的目標利潤率概況的演變？

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

偉大的。薩爾文，關於分子反應的第一個問題，我先交給帕布羅回答，之後我再回答你關於營運績效的問題。

Thank you for the question, Salveen. 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. One is VAF in [whole] blood. The other one is CD34-positive mutant CALR cells in peripheral blood mononuclear cells. And the thirds is malignant megakaryocytes or mutant CALR megakaryocytes in the bone marrow.

謝謝你的提問，薩爾文。所以，我們有三個——重要的是要記住，我們有三個分子終點，我們將在年底前報告相關數據。其中之一是全血中的VAF。另一種是周邊血單核細胞中的 CD34 陽性突變 CALR 細胞。第三類是骨髓的惡性巨核細胞或突變 CALR 巨核細胞。

And the reason why emphasizing those three, because VAF is in a way, a lagging indicator of what's happening to bone marrow, which is what truly matters. The disease originates in the bone marrow and reducing malignant megakaryocytes in the bone marrow, which is something we showed for ET at EHA this year, is the critical disease-modifying effect. That then will translate into reduction of CD34-positive mutant CALR (inaudible) cells in peripheral blood and that, in turn, over time, will be reflected in a reduction in VAF.

之所以要強調這三點，是因為 VAF 在某種意義上是骨髓狀況的滯後指標，而骨髓狀況才是真正重要的。該疾病起源於骨髓，減少骨髓中的惡性巨核細胞（這是我們今年在 EHA 上針對 ET 所展示的）是關鍵的疾病修飾作用。這將導致周邊血液中 CD34 陽性突變 CALR（聽不清楚）細胞減少，進而隨著時間的推移，這將反映在 VAF 的減少上。

So I think I would emphasize that it's important to look at all three components of the transaction endpoints, 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, and we've shown some data in ET that patients with lower VAF -- slightly higher VAF reductions over time, have better hematologic responses in ET.

所以我認為應該強調的是，必須關注交易端點的所有三個組成部分，我們將在年底前討論這三個方面。就相關性而言，我們知道 VAF 不好，我們在 ET 中也發現了一些數據，表明 VAF 較低的患者（隨著時間的推移，VAF 下降幅度略高）在 ET 中具有更好的血液學反應。

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

這些數據很重要。我們仍然相信，989 的初步批准很可能主要基於臨床終點、傳統臨床終點，以及我們已知的終點組合，即脾臟、症狀和貧血，而這正是我們為明年進行關鍵性試驗的方式。我把它轉交給比爾。

Yeah. Thanks, Pablo. And as it relates to OpEx, Salveen, 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 multiyear view of the budget. And I'm not necessarily hard coding for OpEx as a percentage, or R&D as a percentage of sales. 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.

是的。謝謝你，帕布羅。至於營運支出方面，Salveen，這確實是個好問題。我花了很多時間思考這個問題。正如你在問題中所暗示的那樣，我們必須從多年角度看待預算。我並沒有刻意將營運支出（OpEx）或研發支出（RCOND）設定為銷售額的百分比。但我預計至少支出成長的幅度或百分比將會下降，我預期下降的原因是銷售額和槓桿率的提高。

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. Or another way to put it is good cost from bad costs. 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.

我想說的是，每一美元的研發投入和每一美元的銷售、管理及行政費用都必須服務於業務策略，而預算編制的目的就在於區分高價值項目和低價值項目，正如你所知。換句話說，就是從不良成本中獲得良好效益。但我們真正要解決的問題是，如何在 2029 年後創造盡可能陡峭的成長曲線，以及長期的收入和現金流。

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 in part due to increasing sales and good cost control.

我們將盡可能精簡成本，但不會削減關鍵項目的資金，從而損害成長。這就是——這些是我思考營運支出時遵循的原則，而且我預計隨著時間的推移，由於銷售額的成長和良好的成本控制，我們的利潤率將會提高。

Peter Lawson, Barclays.

Peter Lawson，巴克萊銀行。

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

謝謝您回答問題。Niktimvo，這種成長軌跡的可持續性如何？本季業績相當亮眼，我想知道您是否也能談談該特許經營權的盈利情況。

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

彼得，你能再重複一次問題嗎？有點難以聽清楚。

Oh, yeah, sorry. On Niktimvo, if you could talk through the sustainability of the trajectory, it was really impressive this quarter, and if you could talk through the profitability as well.

哦，是啊，不好意思。關於 Niktimvo，如果您能談談其發展軌蹟的可持續性，本季度的表現確實令人印象深刻；如果您也能談談其盈利能力，那就更好了。

Yeah. I'll start off, and if Mohamed, who runs that business, has any additional comments, he can contribute too.

是的。我先來，如果經營這家企業的穆罕默德還有什麼補充意見，他也可以發表。

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 Niktimvo, which I think is very, very encouraging. All the feedback we've got from transplanters is very, very positive.

你說得對。開局非常非常好。我們每年的收入接近 2 億美元。我認為目前這次發布的重要意義在於，美國幾乎所有的 BMT 中心都在使用和購買 Niktimvo，我認為這非常令人鼓舞。我們從移植者那裡得到的所有回饋都非常非常積極。

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 Rezurock curve, when it launched, we're virtually right on top of it. That product, they had a tough quarter, but it's roughly a $500 million business.

如您所知，我們正處於產品發布的第三、第四季度，而產品發布初期每季的情況都可能難以預測。我只能說，我認為它目前的成長勢頭很穩健。如果你看 Rezurock 的發展曲線，你會發現它剛推出時，我們幾乎剛好處於曲線的頂端。他們那款產品本季業績不佳，但它仍然是一項價值約 5 億美元的業務。

So I think the prospects for growth next year are solid. We'll, of course, share guidance in early 2026, but I don't see any red flags right now other than launches can be a little bit unpredictable and uncertain, but I like the way it looks.

所以我認為明年的成長前景良好。我們當然會在 2026 年初分享指導意見，但目前除了產品發布可能有點難以預測和不確定之外，我沒有看到任何危險信號，但我喜歡它現在的樣子。

The next comment I would make as it relates to profitability, one of the nice things about this product is it's a specialty product, 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. And so when you look at the margin profile of a product like this, it's very healthy. That's what I can tell you about profitability. I wish more of them were as profitable as Niktimvo.

接下來我想談談獲利能力，這款產品的優點之一是它是一款專業產品，我們並沒有涵蓋 10,000、20,000、30,000 名醫生或數千家醫院。我們的目標受眾非常明確，涵蓋了全美各地的骨髓移植中心。因此，當你觀察這類產品的利潤率時，你會發現它的利潤率非常健康。這就是我能告訴你的關於盈利能力的資訊。我希望更多公司能像 Niktimvo 一樣獲利。

Mohamed, do you have anything else you want to add?

穆罕默德，你還有什麼要補充的嗎？

Yeah, thanks, Bill. Maybe just to compliment and give you some color on the sustainability of the growth. As Bill mentioned, a really broad penetration with 90% of transplant centers picking up Niktimvo, 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.

是啊，謝謝你，比爾。或許只是想補充一些關於成長可持續性的資訊。正如比爾所提到的，Niktimvo 的滲透率非常高，90% 的移植中心都選擇了它，而且我們看到所有這些中心今年都下了重複訂單，這不僅說明了試用情況，也說明了這些客戶中的重複使用情況，而且反饋也一直很積極。

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, 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.

關於該發展軌蹟的可持續性，還有一點是，正如我們預期的那樣，目前大部分利用率都發生在第四線，但我們看到第三線設置越來越受歡迎，而且這種受歡迎程度還在不斷提高，這給我們留下了很大的發展空間。關於永續性，或許還有最後一點需要說明，我們在上次電話會議上提出的目標是，到年底時有大約 1000 名活躍患者接受治療。

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. And then from a contribution margin, maybe just the last note is, this contribution margin for the Niktimvo 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.

前九個月，我們大約有 800 名患者，正朝著年底達到 1000 名患者的目標穩步前進，而且這一趨勢也持續令人鼓舞。最後，從貢獻毛利來看，或許最後一點需要說明的是，Niktimvo 損益表的貢獻毛利在我們所有產品組合中屬於較高水平，鑑於我們對產品的關注程度以及在商業執行方面的關注程度，我們預計這種情況還會繼續保持下去。

Great. Thanks, Mohamed.

偉大的。謝謝你，穆罕默德。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO資本市場。

Thanks for taking the question. Great to see a lot of you at ESMO. So I think we'd all agree that mCALR is a very critical juncture for Incyte, but I want to take it out of the picture for a second. So can you walk me through how the current pipeline needs to mature to drive growth through the Jakafi LOE? 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?

感謝您回答這個問題。很高興在ESMO見到你們中的許多人。所以我想我們都會同意，mCALR 對 Incyte 來說是一個非常關鍵的時刻，但我想暫時把它排除在外。那麼，您能否詳細介紹一下，目前的管道需要如何完善才能透過 Jakafi LOE 推動成長？那麼，為了促進業務成長，您需要採取哪些類型的業務拓展措施？ （您不會具體說明）

Essentially, I want to understand what Incyte looks like with and without mCALR by the end of the decade.

從本質上講，我希望了解到本十年末，Incyte 在有 mCALR 和沒有 mCALR 的情況下會是什麼樣子。

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. And not all of them have to work. Not all of them will work. We're not going to be perfect. But 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.

是的，很高興在ESMO上見到你。以下是我對這條管道的理解。我們專注於七個驅動因素，七個項目，我認為它們有潛力創造非常有意義的價值。而且並非所有人都必須工作。並非所有方法都有效。我們不可能做到完美。但我們有Povorcitinib，它是一種具有三種適應症的產品。我們可以在皮膚科領域建立以 Jak 為核心的特許經營體系，因為我們擁有差異化的知識和能力以及非常可靠的數據集。

The second project is 989, and I can't take it out of the picture, Evan, okay? 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. In fact, it could be two exercises of a 989.

第二個項目是 989，我不能把它從計劃中剔除，埃文，好嗎？那是一個重要的項目。我們有 617F，它仍處於早期階段，不太透明，但隨著我們降低該資產的風險，它在 MPN 中的規模可能與 989 相當甚至更大，因為它涵蓋了一種更常見的突變。事實上，這可能是 989 的兩次練習。

Then we have three solid tumor programs, which we de-risked at ESMO. We still have more data to collect. You have G12D for pancreatic cancer, TGF by PD1 for CRC, and CDK2 for ovarian cancer. What I would say here is that we're systematically and deliberately, and at least up until ESMO, quietly building a high-impact oncology portfolio. There is a lot of substrate there. I don't expect all these necessarily to work, all right? But if one or two of those hit, they could be very, very meaningful.

然後我們有三個實體腫瘤項目，我們在 ESMO 上降低了這些項目的風險。我們還需要收集更多數據。您患有胰腺癌的 G12D、CRC 的 PD1 介導的 TGF 和卵巢癌的 CDK2。我想說的是，我們一直在有條不紊、有計劃地，至少在 ESMO 大會之前，悄悄地建立一個具有重大影響的腫瘤產品組合。那裡有很多基質。我並不期待這些方法都一定有效，好嗎？但如果其中一兩項命中，可能會產生非常非常大的影響。

As we talked about at the start of the call, novel compounds against novel biological targets in cancers that have missed the IO revolution where there's significant medical need, and we're positioning all three compounds frontline in combination with standard of care chemo. And then the seventh project that I focus on is Niktimvo. And as Mohammed talked about, we're off to a good start, and there was a question about sustainability.

正如我們在電話會議開始時所討論的，針對那些錯過了免疫腫瘤革命、存在重大醫療需求的癌症中的新型生物靶點，我們正在研發新型化合物，並將這三種化合物與標準化療聯合用於一線治療。然後，我重點關注的第七個項目是 Niktimvo。正如穆罕默德所說，我們開局良好，並且有一個關於永續性的問題。

We have two combination trials in place. If one of those combination trials hit, and 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. And so when you think about the flow across all of our three verticals, I&I, 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 ones that we have post-2029.

我們目前有兩項聯合試驗正在進行中。如果其中一項組合試驗成功，而我們兩次試驗中成功一次，我們就將其移至第二行。如果是與 Jakafi 的聯合試驗，我們有一種非類固醇療法，你可以讓這項業務的價值翻倍。因此，當你考慮我們所有三個垂直領域（感染與感染、血液學和腫瘤學）的流程時，你會發現其中存在一些真正的基礎，我們不需要做到完美。在這七個目標中，我們只需要達成兩到三個，到 2029 年以後，我們就能建立一個比我們現有業務更大的企業。

Derek Archila, Wells Fargo.

Derek Archila，富國銀行。

Thanks for taking the questions. Just curious for 989 pivotal trials in MF and ET expected next year. Will these be with IV with the on-body pump from Enfuse? And then just a quick follow up. In terms of a potential XR launch and kind of the 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.

謝謝您回答問題。只是好奇明年預計進行的 989 項 MF 和 ET 關鍵性試驗。這些藥物會透過 Enfuse 公司的體外輸液幫浦進行靜脈輸注嗎？然後，再補充一個簡單的問題。就潛在的 XR 發布以及在準備好的發言稿中對發布計劃的評論而言，我想知道你們打算如何與支付方進行溝通？那麼，你基本上可以轉換多少 Jakafi 仿製藥的股份呢？

Yeah, good question. I will 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.

嗯，問得好。我將對 Enable 和 XR 發表一些評論，然後向 Pablo 和 Mohamed 提問。首先，我們非常高興能與 Enable 建立合作關係。他們專注於大容量皮下給藥，產品容量範圍為 5 毫升至 25 毫升。我們也喜歡這款設備，因為它方便在家中自行使用，舒適便捷，而且他們的生產運作效率很高，我認為這是一家高品質的公司。

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. And so this is a high-quality company. Pablo can talk more about the program. As it relates to XR -- let's just -- Pablo, why don't you speak and then we'll go to XR.

他們正在擴建其生產基地，該生產基地已獲得 FDA 批准，他們的商業設備據我所知已銷往約 25 個國家，銷售約 8,000 台。所以這是一家高品質的公司。巴勃羅可以詳細介紹一下這個專案。至於 XR——我們先來說說——Pablo，你先說幾句，然後我們再討論 XR。

So in terms of the plan to incorporating Enfuse into the pivotal trials in MPNs, ET is pretty far along. We showed an update at EHA a few months ago on the data. The data has continued to mature. We have already initiated regulatory interactions around that. So we're probably going to be ready to start pivotal trial in ET before we're ready to deploy the Enfuse device.

因此，就將 Enfuse 納入 MPN 的關鍵試驗的計劃而言，ET 已經取得了相當大的進展。幾個月前，我們在歐洲健康聯盟 (EHA) 上展示了最新的數據。數據持續完善。我們已經就此展開了監管方面的溝通。因此，我們可能要等到準備好部署 Enfuse 設備之後，才能開始在 ET 進行關鍵性試驗。

For MF, the goal is to do as quickly as possible, make the Enfuse device available and ready to go so we can start those studies with the subcu administration. However, I can't 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.

對於 MF 而言，目標是盡快使 Enfuse 設備可用並準備就緒，以便我們可以開始進行皮下給藥的研究。但是，我現在還不能下定決心。我們需要更多時間來真正確定實施該方案的時間安排，但這將是我們MF的目標。

Mohamed, you want to talk about XR?

穆罕默德，你想聊聊XR嗎？

Yeah, if I can put that in frame for us real quick, Derek. Jakafi at 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.

是的，德瑞克，如果我能盡快把這件事說明一下的話。如您所知，Jakafi at XR 是預計 2026 年年中推出的產品組合的另一個重要補充。醫護人員和患者現在可以方便地每天服用一次他們熟悉和信賴的品牌產品。我們預計到 2028 年，IR 的轉換率將達到 15% 至 30%。

And with a slower erosion curve than IR, 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. And if I can just point to our ability to launch Niktimvo, FL in Monjuvi, and Zynyz in SCAC, I'm just proud of our team's ability to execute on these launches, and I think XR won't be any different.

與 IR 相比，XR 的侵蝕曲線較慢，因此到 2030 年及以後，XR 可以成為營收成長的穩定貢獻者。正如您所提到的，我們的上市策略著重於確保快速納入處方集、加速醫護人員採用以及提高病患偏好，從而在短期內最大限度地提高產品普及率，以實現長期價值。如果我只以我們成功推出 Niktimvo、Monjuvi 的 FL 和 SCAC 的 Zynyz 為例，我就會為我們團隊執行這些專案的能力感到自豪，我認為 XR 也不會例外。

Great. Thanks, Mohamed.

偉大的。謝謝你，穆罕默德。

Ash Verma, UBS.

阿什維爾馬，瑞銀集團。

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

感謝您耐心解答我們的問題。所以，是的，我們非常關注989。就像看看這張投影片 20 一樣，你在 ET 和 MF 中探索了一些不同的設置，但目前我只想確認一下，你是否能夠在註冊研究中招募一線或初治患者。其次，關於配方，例如如何將體積減少到多少毫升，以及這種配方是否可以進行皮下注射，而不僅僅是塗抹在身上？

Thanks, Ash. Pablo, you want to take that?

謝謝你，阿什。巴勃羅，你想拿那個嗎？

Soni, thank you for the question. So 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.

索尼，謝謝你的提問。所以我認為第一部分是關於一線 MF 的，答案是我們完全打算將 989 開發為第一線骨髓纖維化患者。這就是為什麼我們要在未經治療的患者中採用魯索替尼聯合治療的原因。這項工作仍在進行中。我們不會在今年年底前公佈相關結果，但我相信我們一定能找到解決方案。

We have very clear preclinical data showing synergy between 989 and Ruxolitinib in the right models of MF. 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 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.

我們有非常明確的臨床前數據表明，在合適的 MF 模型中，989 和魯索替尼之間存在協同作用。所以我相信我們一定能找到出路。就皮下注射而言，我們的目標是研發一種患者可以在家中自行皮下注射 989 的設備。這就是目標。這就是為什麼我們與 Enable 展開合作的原因，我們認為我們將在 2026 年找到實現這一目標的途徑。

Thanks, Pablo.

謝謝你，帕布羅。

Reni Benjamin, Citizens Reliance.

雷尼‧班傑明，公民信賴組織。

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 LOE. 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 Rux?

感謝您回答問題，並祝賀您本季取得了優異的成績。我想繼續跟進 Rux XR，很久以前曾有一個策略是將其與管道產品結合起來，以幫助對抗這種 LOE。您是否正在考慮任何可能的組合方案，以推進產品線開發或引進產品，從而阻止 Rux 的這種下滑趨勢？

And as a follow up, you're starting this registrational program with TGF-beta. I'm kind of curious as you think about how large the study is, the delta that you need to show to have a positive study, how you come to the calculus given the kind of limited data that you have so far?

作為後續工作，你們將啟動 TGF-β 的註冊計畫。我很好奇，當你思考這項研究的規模有多大，你需要證明多大的變化才能得出陽性結果時，鑑於你目前掌握的有限數據，你是如何進行計算的？

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

我拿第一個，把第二個交給巴布羅。目前，我們 XR 的重點是將其應用於 Jakafi 適應症。我們目前沒有在發展任何組合方案，也沒有這方面的計畫。我知道這其中有一段歷史，但我們現在只專注於每天一次的給藥方案，以保留一部分收入來源，並推出更方便的給藥方案。至於你的第二個問題，我會把它交給史蒂文·斯坦來回答。

So it's first-line microsatellite-stable colorectal cancer. The combination will be advanced in there, as we alluded to at ESMO, is with Folfox and Bev. That's used across the board, independent of [RAS], mutant versus wild-type, independent of left or right-sided tumor. The enabling safety work has already progressed well and will continue. There's benchmarks available both for progression-free survival as well as overall survival.

所以這是微衛星穩定型大腸直腸癌的第一線治療方案。正如我們在 ESMO 上提到的那樣，Folfox 和 Bev 將在那裡推進這一組合。無論 [RAS] 是否突變、突變型或野生型、腫瘤位於左側或右側，都適用此方法。前期安全準備工作進展順利，並將繼續進行。既有無惡化存活期的基準，也有總存活期的基準。

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, but you can estimate it's probably north of 500, and we'll be well-powered to show the PFS advantage we want.

正如我們在 ASH 會議上提到的，主要終點將是 PFS，因為 OS 需要更長的時間才能達到 PFS。我們在啟動研究時會公佈樣本量，但你可以估計樣本量可能超過 500，我們將有足夠的統計效力來證明我們想要的 PFS 優勢。

Thanks, Steven.

謝謝你，史蒂文。

Jessica Fye, JPMorgan.

潔西卡費伊，摩根大通。

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-Jakafi patients and Jakafi suboptimal responders could make us come away confident that 989 could be successful in the frontline?

謝謝您回答我的問題。我在989上還有幾個。所以我想，Pablo，考慮到到年底我們可能還沒有 989 的一線數據，你能談談在接受 Jakafi 治療後的患者和對 Jakafi 反應欠佳的患者中，哪些數據要素可以讓我們確信 989 能夠在一線治療中取得成功嗎？

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 had the patients just remained on their Jakafi monotherapy? And I have a follow up.

我想具體來說，對於這個組合資料集，我知道它比較小，但在沒有對照組的情況下，您會尋找哪些證據來證明 989 在 Jakafi 的基礎上提供了明顯的臨床益處？在這些關鍵指標上，與基線相比是否存在一定程度的變化，您認為這可以排除患者繼續接受 Jakafi 單藥治療後終點指標隨時間推移出現的自然變異性嗎？我還有一個後續問題。

Thanks, Jess. 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. 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. And because of the exclusively targeted nature of 989, we think that the safety profile, the really excellent problem that we've shown so far, is a key element for the future development.

謝謝你，傑西。我認為，就像任何早期開發項目一樣，早期開發階段的項目，全面審視所有新出現的證據非常重要。所以，首先顯然是要考察安全性。我們今年早些時候在《ET》中已經展示過這一點。我們將在今年年底前在MF上展示它。正因為 989 具有專門針對特定人群的性質，我們認為其安全性（我們迄今為止所展現的真正卓越的問題）是未來發展的關鍵要素。

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 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.

第二部分顯然是功效。正如我前面提到的，這兩個組成部分顯然是經典的臨床終點。我們需要觀察對 Jakafi 有抗藥性、不耐受或不適合接受 Jakafi 治療的患者，單藥治療的效果，以及對臨床終點、脾臟縮小、症狀改善、貧血改善以及轉化終點的明確影響。

Now, when you look at the add-on cohort that we're going to show some data, I think it's important to remember that those are the hardest patients to treat. Those are patients that did not respond to Jakafi in an ideal way despite a minimum of 12 weeks of treatment and being eight weeks on a stable dose. So any improvement on classic endpoints in those patients we think is highly meaningful.

現在，當我們查看即將展示一些數據的附加隊列時，我認為重要的是要記住，這些是最難治療的患者。這些患者儘管接受了至少 12 週的治療，並且穩定服用劑量 8 週，但對 Jakafi 的反應並不理想。因此，我們認為這些患者在經典終點指標上的任何改善都具有非常重要的意義。

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. So in our view, when you combine the monotherapy data in the 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 and our ability to move 989 to the frontline setting as quickly as possible.

當你查看二線MF的可用產品時，你會發現它們的基準性能相當低，正如我之前提到的，例如SVR35的性能在9%到20%之間。因此，我們認為，將二線單藥治療數據與 989 與 Jakafi 聯合使用的能力以及安全性結合起來，很容易就能得出這樣的結論：這將增強我們的信心，並使我們能夠盡快將 989 推向一線治療。

Obviously, at some point in 2026, we'll provide an update on the treatment of naive patients, as I mentioned earlier, and that sort of will be the definitive element of that story.

顯然，正如我之前提到的，在 2026 年的某個時候，我們將提供關於初治患者治療的最新信息，而那將是這個故事的決定性因素。

You mentioned looking at SVR25 in addition to SVR35. How do you incorporate SVR25 data into your decision-making?

您提到除了SVR35之外，還要考慮SVR25。您如何將SVR25資料納入決策過程？

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. So we think it's important to have directional data where the spleen shrinkage is going.

我們真的沒有。坦白說，我們報告了 25 和 35 這兩個結果，就像過去在其他試驗中所做的那樣。部分患者的追蹤時間相對較短。我們有患者接受了不同劑量的治療。如您所知，這些是劑量遞增試驗。因此，我們認為掌握脾臟萎縮的方向性資料非常重要。

But the key element here is SVR35. Make no mistake about that. We report 25 as well, but SVR 35 is what we really care about.

但關鍵在於 SVR35。這點毋庸置疑。我們也報告了 25，但我們真正關心的是 SVR 35。

Kripa Devarakonda, Truist Securities.

Kripa Devarakonda，Truist 證券公司。

Thank you so much for taking my question. Another one on 989. So when it comes to a Rux combo, is there a rationale to develop both in suboptimal responders as well as in Rux-naive patients, or do you see it as a better strategy to focus on one versus the other for the longer term?

非常感謝您回答我的問題。989號也有一起。那麼，對於魯拉西坦聯合療法，對於療效欠佳的患者以及未接受過魯拉西坦治療的患者，是否有必要同時開發這兩種療法？或者，從長遠來看，專注於其中一種療法比專注於另一種療法是否是更好的策略？

And secondly, what's the FDA guidance for the endpoints? Now, I know you said you need to show both SVR35 and TSS50, but would they be co-primary endpoints? And do you have to hit on both?

其次，FDA對終點指標的指導意見是什麼？我知道您說過需要同時展示 SVR35 和 TSS50，但它們會是共同的主要終點嗎？難道你必須兩個都上嗎？

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 MS, 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.

讓我先回答問題的第二部分。我們會與 FDA 討論針對 MS 患者的新型治療模式的適當監管終點，我們認為 989 就代表了這種模式。我們認為這將主要基於臨床終點。具體臨床終點是什麼，我們會和FDA討論。

We think there's an argument to be made about modifying some of what has been done previously in terms of co-primaries for SVR35 and TSS50. The impact on anemia, for example, we think could be very important and very interesting for FDA to contemplate.

我們認為，對於 SVR35 和 TSS50 的共同主要指標，有必要對先前的一些做法進行修改。例如，我們認為，對貧血的影響可能非常重要，也是FDA應該認真考慮的問題。

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. But 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. And in those two contexts, monotherapy and in combination with Ruxolitinib potentially can have a role.

至於我們將在 MF 中進行哪些關鍵性試驗，這些決定正在製定中，我們會不時更新信息，可能在 2026 年初。但我們計劃開發 989，以滿足所有 CALR 突變陽性 MF 患者的需求。這包括初次接受治療的患者，以及最初接受 Jakafi 治療但未產生療效或無法耐受的患者。在這兩種情況下，單藥治療和與魯索替尼聯合治療都可能發揮作用。

We'll give you more details over time as we disclose the data.

隨著數據的逐步披露，我們會陸續提供更多細節。

Great. Thanks Pablo.

偉大的。謝謝你，帕布羅。

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

謝謝。我們的問答環節到此結束，今天的電話會議和網路直播也到此結束。現在您可以斷開線路了，祝您有美好的一天。感謝您今天的參與。