英賽德 (INCY) 2024 Q3 法說會逐字稿

Greetings, and welcome to the Incyte third-quarter financial results conference call and webcast. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Incyte 第三季財務業績電話會議和網路廣播。（操作員指示）謹此提醒，本次會議正在錄製中。

It's now my pleasure to turn the call over to Ben Strain, Associate Vice President, Investor Relations. Please go ahead, Ben.

現在我很高興將電話轉給投資人關係副總裁 Ben Strain。請繼續，本。

Thank you, Kevin. Good morning, and welcome to Incyte's third-quarter 2024 earnings conference call. Before we begin, I encourage everyone to go to the Investors section of the website to find the press release, related financial tables and slides that follow today's discussion. On today's call, I'm joined by Hervé, Pablo, Christiana, who will deliver our prepared remarks. Barry, Matteo and Steven will also be available for Q&A.

謝謝你，凱文。早安，歡迎參加 Incyte 2024 年第三季財報電話會議。在我們開始之前，我鼓勵大家造訪網站的投資者部分，尋找今天討論之後的新聞稿、相關財務表格和幻燈片。在今天的電話會議上，艾爾韋、巴布羅、克里斯蒂安娜也將加入我的行列，他們將發表我們準備好的演講。巴里、馬泰奧和史蒂文也將出席問答環節。

I would like to point out that we'll 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.

我想指出的是，我們將根據我們目前的期望和信念做出前瞻性聲明。這些陳述存在一定的風險和不確定性，我們的實際結果可能有重大差異。我鼓勵您查閱我們向 SEC 提交的文件中討論的風險因素，以了解更多詳細資訊。

I will now hand the call over to Hervé.

現在我將把電話轉交給 Herve。

Thank you, Ben, and good morning, everyone. The third quarter of 2024 was a very positive quarter for Incyte with a good commercial performance, FDA approval of Niktimvo, and progress of our pipeline with several key data readouts for our clinical programs.

謝謝你，本，大家早安。2024 年第三季度對 Incyte 來說是一個非常積極的季度，其商業表現良好，Niktimvo 得到 FDA 批准，我們的管道取得了進展，並公佈了我們臨床計畫的幾個關鍵數據。

In Q3, total revenues increased by 24% year over year to $1.1 billion, with net product revenues growing 23%. This growth was driven by the ongoing demand growth for Jakafi and Opzelura, which I will highlight in the following slides. In August, we, along with our partner, Syndax, announced the FDA approval of Niktimvo for patients with chronic graft-versus-host disease after failure of two prior lines of therapy, making it the first anti-CSF-1R antibody approved to target the inflammation and fibrosis associated with chronic GVHD.

第三季度，總營收年增 24%，達到 11 億美元，產品淨收入成長 23%。這一成長是由 Jakafi 和 Opzelura 的持續需求成長所推動的，我將在下面的幻燈片中重點介紹這一點。8 月，我們與我們的合作夥伴Syndax 一起宣布FDA 批准Niktimvo 用於治療先前兩種療法失敗後的慢性移植物抗宿主病患者，使其成為第一個被批准用於標靶治療的抗CSF- 1R 抗體與慢性 GVHD 相關的發炎和纖維化。

To facilitate patient dosing and limit product waste following the FDA's approval of Niktimvo, we have submitted two smaller vial sizes to the FDA for the approval. Following the potential approval of the new vial sizes, we anticipate launching Niktimvo in the US in the first quarter of 2025.

在 FDA 批准 Niktimvo 後，為了方便患者給藥並限制產品浪費，我們已向 FDA 提交了兩個較小的小瓶尺寸以供批准。在新的小瓶尺寸可能獲得批准後，我們預計將於 2025 年第一季在美國推出 Niktimvo。

Additionally, the positive pivotal AGAVE-201 trial results were recently published in the New England Journal of Medicine. Niktimvo was also included in the latest NCCN Clinical Practice Guidelines in Oncology for chronic GVHD treatment, both highlighting the significance of this dataset and the transformative potential of Niktimvo. The sNDA for ruxolitinib cream in pediatric atopic dermatitis was recently filed with the FDA, and we are on track for a potential approval in the second half of 2025.

此外，積極的關鍵 AGAVE-201 試驗結果最近發表在《新英格蘭醫學雜誌》。Niktimvo 也被納入最新的 NCCN 慢性 GVHD 治療腫瘤學臨床實踐指南，這都強調了該資料集的重要性和 Niktimvo 的變革潛力。魯索替尼乳膏治療兒童異位性皮膚炎的 sNDA 最近已向 FDA 提交，我們預計在 2025 年下半年獲得批准。

During the quarter, we also provided important clinical updates at ESMO with encouraging data for our CDK2 inhibitor in ovarian and endometrial cancer as well as data from the Phase 3 trial of retifanlimab in SCAC. At EADV, we presented extensive data on both povorcitinib and ruxolitinib cream, including multiple lead-breaking presentations that showed the potential of this program to enhance treatment options for individuals with immune mediated dermatologic conditions such as vitiligo, atopic dermatitis, hidradenitis suppurativa, and prurigo nodularis.

在本季度，我們還在 ESMO 上提供了重要的臨床更新，包括我們的 CDK2 抑制劑在卵巢癌和子宮內膜癌中的令人鼓舞的數據，以及 SCAC 中 retifanlimab 3 期試驗的數據。在EADV 上，我們提供了有關povorcitinib 和ruxolitinib 乳膏的大量數據，包括多個突破性的演示，表明該計劃有可能增強患有白癜風、特應性皮膚炎、化膿性汗腺炎和癢疹等免疫介導皮膚病患者的治療選擇結節狀。

Moving to slide 6 and an update of the third-quarter commercial performance of Jakafi. Jakafi net product revenue were $731 million, up 16% year over year. Paid demand increased 10%, driven by patient growth across all indications. Based on the strength in demand seen during the first three quarters of 2024, we are raising our full-year 2024 Jakafi net revenue guidance to a new range of $2.74 billion to $2.77 billion.

轉到投影片 6，更新 Jakafi 第三季的商業表現。Jakafi 產品淨收入為 7.31 億美元，較去年同期成長 16%。在所有適應症患者成長的推動下，付費需求增加了 10%。根據 2024 年前三個季度的強勁需求，我們將 2024 年全年 Jakafi 淨收入指引上調至 27.4 億美元至 27.7 億美元的新範圍。

Turning to slide 7 and looking at Jakafi total paid demand by indication during the first nine months of 2022, '23 and '24. As you can see, unit growth remains robust. Myelofibrosis is stable year over year with some modest growth seen again this quarter, while the most significant growth is seen in polycythemia vera and graft-versus-host disease. We expect PV to become the largest contributor for Jakafi over time, supported by the data from the MAJIC-PV study, which underscores the benefit of early intervention with Jakafi and its impact on thrombosis-free survival.

轉向幻燈片 7，查看 2022 年前 9 個月、23 年和 24 年期間 Jakafi 的總付費需求。正如您所看到的，單位成長仍然強勁。骨髓纖維化同比穩定，本季再次出現小幅增長，而最顯著的增長出現在真性紅血球增多症和移植物抗宿主疾病中。我們預計，隨著時間的推移，PV 將成為 Jakafi 的最大貢獻者，MAJIC-PV 研究的數據也支持了這一點，該研究強調了 Jakafi 早期介入的益處及其對無血栓存活期的影響。

Moving to Opzelura on slide 8, total Opzelura net product revenues in the third quarter were $139 million, up 52% when compared to the same quarter last year. In the US, the annual prescription trends for 2022 and '23 and year-to-date '24, as shown on the right of the slide 8, reflects continued year-over-year growth of Opzelura from both atopic dermatitis and vitiligo.

轉到幻燈片 8 上的 Opzelura，第三季 Opzelura 淨產品總收入為 1.39 億美元，比去年同期成長 52%。在美國，2022 年和 23 年以及年初至今的 24 年年度處方趨勢（如幻燈片 8 右側所示）反映了 Opzelura 治療異位性皮膚炎和白斑症的逐年持續增長。

During the third quarter, we continued to progress with the launch of Opzelura in Europe to $20 million, [and] net sales during the third quarter were driven by France, where Opzelura is now reimbursed and available in retail pharmacy and from Germany. Earlier this month, we also achieved approval for atopic dermatitis and vitiligo in Canada.

第三季度，我們繼續取得進展，Opzelura 在歐洲的上市銷售額達到了 2000 萬美元，第三季度的淨銷售額由法國推動，Opzelura 現在在法國可以報銷，可以在零售藥局和德國購買。本月早些時候，我們還在加拿大獲得了治療異位性皮膚炎和白斑症的批准。

On slide 9, I want to highlight three products that are expected to begin contributing to revenue in the near term. We anticipate that Niktimvo for third-line chronic GVHD, tafasitamab for follicular lymphoma, and retifanlimab for SCAC could collectively generate $800 million or more in incremental revenues by 2029. We anticipate all three products to be available in 2025, and this incremental sales will be leveraging the current commercial infrastructure used for Monjuvi, Pemazyre and Jakafi.

在投影片 9 上，我想強調三種預計在短期內開始貢獻收入的產品。我們預計，到 2029 年，治療三線慢性 GVHD 的 Niktimvo、治療濾泡性淋巴瘤的 tafasitamab 和治療 SCAC 的 retifanlimab 總共可產生 8 億美元或更多的增量收入。我們預計這三種產品將於 2025 年上市，增量銷售將利用 Monjuvi、Pemazyre 和 Jakafi 目前使用的商業基礎設施。

As illustrated on slide 10, these three launches anticipated in 2025 will be followed by larger opportunities in 2026 and 2027, including povorcitinib, CDK2, and tafasitamab in first-line DLBCL. Between 2027 and 2030, we have multiple programs that hold transformative potential with data for each anticipated in 2025.

如投影片 10 所示，預計 2025 年推出的這三項產品將在 2026 年和 2027 年出現更大的機會，包括用於一線 DLBCL 的 povorcitinib、CDK2 和 tafasitamab。2027 年至 2030 年間，我們有多個專案具有變革潛力，每個專案預計在 2025 年都有數據。

I will now turn the call over to Pablo.

我現在將把電話轉給巴勃羅。

Thank you, Hervé, and good morning. As we continue to execute on our pipeline of numerous potential first or best-in-class medicines, we remain on track to deliver more than 10 high-impact launches by 2030. In the next few slides, I will highlight a number of these programs.

謝謝你，埃爾韋，早安。隨著我們繼續開發眾多潛在的首創或同類最佳藥物，我們仍有望在 2030 年之前推出 10 多個高影響力的藥物。在接下來的幾張投影片中，我將重點介紹其中的一些程式。

We continue to expand the opportunity of ruxolitinib cream with additional indications. Based on the positive Phase 3 data in pediatric atopic dermatitis, the supplemental NDA was recently filed. With the potential approval in 2025, we are excited with the possibility of providing an effective nonsteroidal topical option for the two million to three million pediatric patients with AD in the US.

我們繼續擴大魯索替尼乳膏具有其他適應症的機會。基於兒童異位性皮膚炎的積極 3 期數據，最近提交了補充 NDA。隨著 2025 年有望獲得批准，我們很高興能夠為美國 200 萬至 300 萬 AD 兒科患者提供有效的非類固醇外用選擇。

Following interactions with the FDA, we have finalized the design for the Phase 3 study of ruxolitinib cream in patients with mild to moderate hidradenitis suppurativa. The study, which will have a primary endpoint of HiSCR100, is expected to begin in the first half of 2025 and could represent a new treatment option to the approximately 150,000 patients with mild to moderate HS in the US.

經過與 FDA 的互動，我們最終確定了魯索替尼乳膏治療輕至中度化膿性汗腺炎患者的 3 期研究設計。研究的主要終點為 HiSCR100，預計將於 2025 年上半年開始，可能為美國約 15 萬名輕度至中度 HS 患者提供一種新的治療選擇。

As a reminder, we're currently conducting a Phase 3 study evaluating ruxolitinib cream in patients with prurigo nodularis, a chronic skin disorder that presents its multiple firm nodules, commonly located on the extensive surfaces of the extremities and that are intensely pruritic. This pivotal study is enrolling well, and we are now on track to report results in the first half of 2025 with a potential approval as early as 2026. With no topical therapies currently approved for PN and approximately 200,000 patients diagnosed in the US, we see this as an important additional option for patients and a significant opportunity for ruxolitinib cream.

提醒一下，我們目前正在進行一項3 期研究，評估魯索替尼乳膏對結節性癢疹患者的療效，結節性癢疹是一種慢性皮膚病，表現為多個堅硬的結節，通常位於四肢的廣泛表面，並且瘙癢劇烈。這項關鍵研究的招募情況良好，我們現在預計在 2025 年上半年報告結果，並可能最早在 2026 年獲得批准。由於目前尚無批准用於 PN 的局部療法，並且在美國約有 20 萬名患者被診斷出，我們認為這是患者的一個重要的額外選擇，也是魯索替尼乳膏的重要機會。

As shown on slide 15, we're continuing to execute a broad development plan for povorcitinib, our oral small molecule, highly selective JAK1 inhibitor. Povorcitinib is currently being evaluated in Phase 3 studies in hidradenitis suppurativa, vitiligo, and prurigo nodularis and in randomized Phase 2 proof-of-concept studies in asthma and chronic spontaneous urticaria with data for both expected in 2025.

如投影片 15 所示，我們正在繼續執行 povorcitinib（我們的口服小分子高選擇性 JAK1 抑制劑）的廣泛開發計劃。Povorcitinib 目前正在化膿性汗腺炎、白斑症和結節性癢疹的 3 期研究以及氣喘和慢性自發性蕁麻疹的隨機 2 期概念驗證研究中進行評估，預計將於 2025 年獲得這兩項數據。

Povorcitinib has already shown encouraging efficacy and safety in a randomized Phase 2 study involving patients with moderate to severe hidradenitis suppurativa, a highly painful inflammatory condition. As a reminder, we reported that by week 52, up to 29% of patients achieved a HiSCR100 response, indicating complete resolution of all symptoms. Additionally, povorcitinib demonstrated a rapid and significant reduction in pain, offering the opportunity to transform the current standard of care for this disease.

Povorcitinib 在一項隨機 2 期研究中已經顯示出令人鼓舞的療效和安全性，該研究涉及中度至重度化膿性汗腺炎（一種高度疼痛的發炎性疾病）。提醒一下，我們報告稱，到第 52 週，高達 29% 的患者達到了 HiSCR100 反應，表明所有症狀完全消失。此外，povorcitinib 可以快速顯著減輕疼痛，為改變這種疾病的當前治療標準提供了機會。

The two Phase 3 studies, STOP-HS1 and STOP-HS2, are enrolling well, thanks to the strong Phase 2 data and the limited effective treatment options available. We expect to have Phase 3 data by early 2025.

由於強有力的 2 期數據和有限的有效治療方案，兩項 3 期研究 STOP-HS1 和 STOP-HS2 的入組情況良好。我們預計將在 2025 年初獲得第 3 階段的數據。

We have refined our guidance for the Phase 2 proof-of-concept study of povorcitinib in chronic spontaneous urticaria and now anticipate data in the first half of 2025. CSU is a mast cell-driven disease characterized by hives and severe chronic itching. The overactivation of dermal mast cells and basophils leads to increased serum levels of Th1, Th2 and Th17-related cytokines. We know that JAK1 inhibition can modulate mast cell activation, including the granulation and cytokine production, both of which contribute to chronic spontaneous urticaria. This randomized double-blind Phase 2 study is being conducted in patients who are inadequately controlled or have progressed on second-generation antihistamine, which represent a potential patient population of over 300,000 patients in the US alone.

我們已經完善了 povorcitinib 治療慢性自發性蕁麻疹 2 期概念驗證研究的指南，現在預計 2025 年上半年將獲得數據。CSU 是一種肥大細胞驅動的疾病，其特徵是蕁麻疹和嚴重的慢性搔癢。真皮肥大細胞和嗜鹼性粒細胞的過度活化導致 Th1、Th2 和 Th17 相關細胞激素的血清濃度升高。我們知道 JAK1 抑制可以調節肥大細胞激活，包括顆粒形成和細胞因子產生，這兩者都會導致慢性自發性蕁麻疹。這項隨機雙盲 2 期研究是在第二代抗組織胺控制不充分或病情進展的患者中進行的，僅在美國就有超過 30 萬名潛在患者群體。

As you can see on slide 16, our updated inflammation and immunity pipeline continues to evolve. Recently, we presented promising data from our Phase 2 study of ruxolitinib cream in patients with cutaneous lichen planus. At this time, we do not plan to advance ruxolitinib cream into a registrational study for the syndication and intend to publish the results of the study in the future. For lichen sclerosus, given the prioritization of other indications and programs, we are not currently planning to advance this indication into a registrational study. As a reminder, 262 and 547 are currently being evaluated in a number of indications, and we anticipate data for these studies in the first quarter of 2025.

正如您在幻燈片 16 中看到的，我們更新的發炎和免疫管道繼續發展。最近，我們展示了魯索替尼乳膏治療皮膚扁平苔癬患者的 2 期研究的有希望的數據。目前，我們不打算將魯索替尼乳膏推進到聯合用藥的註冊研究中，並打算在未來公佈研究結果。對於硬化性苔蘚，考慮到其他適應症和方案的優先順序，我們目前不打算將該適應症推進註冊研究。提醒一下，目前正在對 262 和 547 的多種適應症進行評估，我們預計這些研究的數據將在 2025 年第一季獲得。

Moving to MPNs and graft-versus-host disease on slide 17. We highlight here a number of ongoing programs where we have the goal of developing new therapeutic options to build upon the significant impact Jakafi has had on patients. Our BET inhibitor dose escalation is ongoing, both as a monotherapy and in combination with ruxolitinib. As a reminder, we have reported reductions in [spring] length and volume as well as improvements in both symptoms and hemoglobin. We plan to advance this program into Phase 3 development and expect to provide an update later this year.

轉到幻燈片 17 上的 MPN 和移植物抗宿主疾病。我們在這裡重點介紹一些正在進行的項目，我們的目標是開發新的治療方案，以增強 Jakafi 對患者的重大影響。我們的 BET 抑制劑劑量持續增加，無論是單一療法或與魯索替尼合併治療。提醒一下，我們報告了[彈簧]長度和體積的減少以及症狀和血紅蛋白的改善。我們計劃將該計劃推進到第三階段開發，並預計在今年稍後提供更新。

Additionally, for zilurgisertib, our ALK2 inhibitor, we plan to provide an update later this year. And for ruxolitinib XR, we plan to share the bioequivalency data in early 2025.

此外，對於我們的 ALK2 抑制劑 zilurgisertib，我們計劃在今年稍後提供更新。對於 ruxolitinib XR，我們計劃在 2025 年初分享生物等效性數據。

Moving to our oncology pipeline on slide 18. We continue to build a robust portfolio with increased emphasis on first-in-class and our best-in-class and novel immuno-oncology programs. For tafasitamab, we shared positive top-line results from the Phase 3 study in patients with follicular lymphoma and we are on track to file the sNDA with the FDA this year, which could lead to a potential approval in 2025. As a reminder, the Phase 3 data for first-line DLBCL in combination with [OS R-CHOP] is expected in the first half of 2025.

前往投影片 18 上我們的腫瘤學研發管線。我們持續建立強大的產品組合，更加重視一流、一流和新穎的免疫腫瘤學課程。對於 tafasitamab，我們分享了濾泡性淋巴瘤患者 3 期研究的積極頂線結果，我們預計今年向 FDA 提交 sNDA，這可能會在 2025 年獲得批准。提醒一下，第一線 DLBCL 聯合 [OS R-CHOP] 的 3 期數據預計將於 2025 年上半年公佈。

During the ESMO conference in September, we shared positive top-line results for the pivotal Phase 3 study of retifanlimab in SCAC. Retifanlimab met the primary endpoint, demonstrating a clinically meaningful 37% reduction in the risk of progression or death with a hazard ratio of 0.63. The study showed that retifanlimab was generally well tolerated and no new safety signals were detected.

在 9 月的 ESMO 會議期間，我們分享了 SCAC 中 retifanlimab 關鍵 3 期研究的正面頂線結果。Retifanlimab 達到了主要終點，顯示進展或死亡風險降低了 37%，具有臨床意義，風險比為 0.63。研究表明，retifanlimab 整體耐受性良好，沒有檢測到新的安全訊號。

At ESMO, we also shared promising evidence of clinical activity from our potentially first-in-class small molecule CDK2 inhibitor, which demonstrated a number of complete and partial responses as well as stable disease in patients with Cyclin E1 overexpressing tumors, most notably in ovarian and endometrial cancer. We believe our CDK2 inhibitor could be a foundational therapy for patients with ovarian cancer as well as other Cyclin E1 overexpressing tumor types, and we plan to move aggressively in initiating registrational studies in 2025. We will be meeting with FDA in the coming months to discuss trial designs. As highlighted on the slide, we're considering different designs for the registrational program, and we will continue to update you on the regulatory strategy for this program in the coming months.

在ESMO，我們也分享了我們潛在的一流小分子CDK2 抑制劑的臨床活性的有希望的證據，該抑制劑在Cyclin E1 過表達腫瘤（尤其是卵巢腫瘤）患者中表現出許多完全和部分緩解以及穩定的疾病和子宮內膜癌。我們相信我們的 CDK2 抑制劑可能成為卵巢癌以及其他 Cyclin E1 過度表現腫瘤類型患者的基礎療法，我們計劃在 2025 年積極啟動註冊研究。我們將在未來幾個月與 FDA 會面討論試驗設計。正如幻燈片中所強調的那樣，我們正在考慮註冊計劃的不同設計，我們將在未來幾個月內繼續向您通報該計劃的監管策略。

In closing, slide 20 shows a summary of the considerable number of milestones across the remainder of 2024 and 2025. These milestones will continue the transformation of our pipeline with a strong focus on new molecular entities with the potential to make an indelible impact on patients.

最後，投影片 20 總結了 2024 年剩餘時間和 2025 年的大量里程碑。這些里程碑將繼續我們的產品線轉型，並專注於可能對患者產生不可磨滅影響的新分子實體。

With that, I would like to turn the call over to Christiana for the financial update.

至此，我想將電話轉給克里斯蒂安娜，了解最新的財務狀況。

Thank you, Pablo, and good morning, everyone. Our third-quarter results reflect strong commercial execution and continued growth with total revenues of $1.14 billion, up 24% versus the same period last year. Total product revenues of $963 million in Q3 were driven by strong demand growth for Jakafi and Opzelura and increased revenue contribution from Monjuvi as a result of the acquisition of full rights to tafasitamab earlier this year. Total royalty revenues were $157 million, up 20% compared to the third quarter of 2023, driven by increased demand for Jakafi and Olumiant.

謝謝你，巴勃羅，大家早安。我們第三季的業績反映了強勁的商業執行力和持續成長，總收入達到 11.4 億美元，比去年同期成長 24%。第三季的產品總收入達到 9.63 億美元，這得益於 Jakafi 和 Opzelura 的強勁需求增長，以及 Monjuvi 由於今年早些時候收購了 tafasitamab 的全部權利而增加的收入貢獻。由於 Jakafi 和 Olumiant 需求增加，特許權使用費總收入為 1.57 億美元，較 2023 年第三季成長 20%。

Turning to Jakafi on slide 24. Jakafi net product revenues were $741 million for the third quarter, reflecting continued demand growth with total demand up 10% year over year, driven by growth in all indications and a $9 million gross to net favorability as a result of true-ups to prior quarter estimates. At the end of Q3, channel inventory was up 2% year over year and stable quarter over quarter and within normal range.

轉向幻燈片 24 上的 Jakafi。Jakafi 第三季產品淨收入為 7.41 億美元，反映出需求持續成長，在所有指標成長的推動下，總需求年增 10%，並且由於上一季的調整，毛淨好感度達到 900 萬美元估計。三季末，通路庫存較去年同期成長2%，季增穩定，處於正常範圍。

Turning now to Opzelura on slide 25, net product revenues for the third quarter were $139 million, representing a 52% year-over-year increase driven by growth in new patient starts and refills across both AD and vitiligo in the US, as well as continued contribution from the commercialization of Opzelura for vitiligo in Europe. In the third quarter, Europe contributed $20 million of Opzelura net product revenues, driven by continued uptake in Germany and broader access in France where Opzelura is now reimbursed and available in retail pharmacies. Third-quarter net product revenues in France include a $2 million stock build up at wholesalers. Finally, in the third quarter, we made significant progress in including Opzelura on regional formularies in Spain and Italy.

現在轉向幻燈片 25 上的 Opzelura，第三季產品淨收入為 1.39 億美元，年成長 52%，這主要得益於美國 AD 和白斑症以及美國 AD 和白斑新患者入院和續藥的成長。白斑症在歐洲商業化的持續貢獻。第三季度，歐洲貢獻了 2000 萬美元的 Opzelura 淨產品收入，這得益於德國的持續使用和法國更廣泛的使用，Opzelura 現在可以報銷並在零售藥局出售。法國第三季產品淨收入包括批發商累積的 200 萬美元庫存。最後，在第三季度，我們在將 Opzelura 納入西班牙和義大利的區域處方集方面取得了重大進展。

Moving on to slide 26 and our operating expenses, total GAAP R&D expenses were $573 million for the third quarter due to the $100 million milestone payment made to MacroGenics during the quarter and continued investment in our late-stage development assets. Excluding all onetime expenses, ongoing R&D expenses for the third quarter increased 26% compared to the same period in '23 due to continued investment in our late-stage development assets, additional R&D expenses resulting from the Escient acquisition, and timing of certain expenses.

繼續看投影片 26 和我們的營運費用，第三季的 GAAP 研發費用總額為 5.73 億美元，這是由於本季度向 MacroGenics 支付了 1 億美元的里程碑付款以及對我們後期開發資產的持續投資。不包括所有一次性費用，第三季的持續研發費用比 2023 年同期成長了 26%，這是由於我們對後期開發資產的持續投資、收購 Escient 產生的額外研發費用以及某些費用的時間表。

For the nine months ended September 30, 2024, ongoing R&D expenses increased 15% compared to the prior year period as a result of increased investment in the Phase 3 studies of povorcitinib and Opzelura. As we wrap up the clinical development of axatilimab in third-line chronic GVHD, tafasitamab in relapsed/refractory follicular lymphoma and retifanlimab in SCAC and non-small cell lung cancer as well as the development activities of discontinued programs, we anticipate the reduction in investment in those programs to partially offset the increased investment in other programs, which would allow us to control future R&D expense growth.

截至 2024 年 9 月 30 日的九個月，由於 povorcitinib 和 Opzelura 3 期研究的投資增加，持續研發費用比去年同期增加了 15%。當我們完成axatilimab治療三線慢性GVHD、tafasitamab治療復發/難治性濾泡性淋巴瘤和retifanlimab治療SCAC和非小細胞肺癌的臨床開發以及已停產項目的開發活動時，我們預計投資會減少這些項目的投資部分抵消了其他項目增加的投資，這將使我們能夠控制未來的研發費用成長。

Moving to SG&A, total GAAP SG&A expenses were $309 million for the third quarter, representing a 15% year-over-year increase primarily driven by timing of consumer marketing activities and certain other expenses. For the nine months ended September 30, total GAAP SG&A expenses increased 6% year over year. Finally, total ongoing operating expenses for the first nine months of the year increased 11% versus a 14% increase in revenues, leading to an increase in operating leverage and margins.

說到銷售及管理費用，第三季 GAAP SG&A 費用總額為 3.09 億美元，年增 15%，這主要是由於消費者行銷活動的時間安排和某些其他費用所致。截至 9 月 30 日的九個月，GAAP SG&A 費用總額年增 6%。最後，今年前 9 個月的持續營運支出總額增加了 11%，而收入增加了 14%，導致營運槓桿和利潤率增加。

Moving on to our guidance for 2024, based on the strong performance of Jakafi in the first nine months of the year, we are increasing our full-year 2024 guidance to a new range of $2.74 billion to $2.77 billion. We are also updating our full-year guidance for other hematology/oncology products to a new range of $310 million to $320 million to reflect the first nine months' actual demand and the unfavorable impact of foreign exchange rates.

接下來是我們對 2024 年的指導，基於 Jakafi 在今年前 9 個月的強勁表現，我們將 2024 年全年指導提高到 27.4 億美元至 27.7 億美元的新範圍。我們也將其他血液學/腫瘤學產品的全年指引更新為 3.1 億至 3.2 億美元的新範圍，以反映前 9 個月的實際需求和外匯匯率的不利影響。

In addition, we are updating the full-year GAAP R&D guidance to include the $100 million milestone payment to MacroGenics. The full-year GAAP R&D guidance is now $2.54 billion to $2.59 billion, which includes $791 million in onetime expenses related to the $691 million of upfront consideration for the acquisition of Escient and the $100 million milestone payment to MacroGenics. Ongoing R&D guidance remains unchanged. Finally, we are reiterating our full-year 2024 guidance for COGS and SG&A.

此外，我們正在更新全年 GAAP 研發指南，其中包括向 MacroGenics 支付 1 億美元的里程碑付款。目前，全年 GAAP 研發指引為 25.4 億美元至 25.9 億美元，其中包括與收購 Escient 的 6.91 億美元預付款相關的 7.91 億美元一次性支出以及向 MacroGenics 支付的 1 億美元里程碑付款。持續的研發指導維持不變。最後，我們重申 2024 年全年 COGS 和 SG&A 指引。

Operator, that concludes our prepared remarks. Please give your instructions and open the call to Q&A.

接線員，我們準備好的發言到此結束。請給出您的指示並打開問答電話。

Certainly. We will now be conducting a question-and-answer session. (Operator Instructions)

當然。我們現在將進行問答環節。（操作員說明）

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Hey, guys. Good morning. Congrats on a great third quarter and thanks for taking my question. I had one on povorcitinib. So just looking ahead to the upcoming Phase 3 data in hidradenitis early next year. So beyond top line success, do you have any thoughts on where you think -- where you want efficacy to shake out in order to be competitive with Humira and other market biologic? Is there a particular placebo-adjusted effect size that you're looking for to hit with povorcitinib? Thanks.

嘿，夥計們。早安.恭喜第三季的出色表現，感謝您提出我的問題。我服用了一種povorcitinib。因此，請期待明年初即將發布的汗腺炎 3 期數據。因此，除了營收成功之外，您對您的想法有何想法 - 您希望在哪些方面發揮功效，以便與 Humira 和其他市場生物製劑競爭？您是否希望使用 povorcitinib 達到特定的安慰劑調整效果量？謝謝。

Michael, it's Steven. Just taking your question. And thank you for the question on HS. Our feeling is if we replicate the Phase 2 data, which was incredibly strong -- and as Pablo said in his prepared remarks, that includes the HiSCR100 of up to 29%, then we'll have an extremely favorable efficacy profile that will really benefit patients with HS.

邁克爾，是史蒂文。只要回答你的問題。感謝您提出有關 HS 的問題。我們的感覺是，如果我們複製2 期數據，該數據非常強勁，正如Pablo 在他準備好的演講中所說，其中包括高達29% 的HiSCR100，那麼我們將獲得極其有利的功效概況，這將真正受益HS 病患。

You couple that with the other symptomatology, particularly the pain from the lesions, and we were able to get in that Phase 2 data set to demonstrate pain relief, and that will add to what we think will be a differentiated profile that will really benefit patients. Obviously, it's hard to predict how Phase 3 will read out.

將其與其他症狀結合起來，特別是病變引起的疼痛，我們能夠獲得第二階段數據集來證明疼痛緩解，這將增加我們認為將真正有益於患者的差異化特徵。顯然，很難預測第三階段的結果如何。

The other thing Pablo alluded to in his prepared remarks is extremely good enrollment on both studies, which is probably a testament to the Phase 2 data driving investigators wanting to put patients on the study. Thanks.

巴勃羅在他準備好的發言中提到的另一件事是這兩項研究的入組率都非常高，這可能證明了二期數據推動研究人員希望將患者納入研究。謝謝。

Jessica Fye, JPMorgan.

潔西卡法耶，摩根大通。

Hey there. Good morning. Thanks for taking my questions. had a few on the pipeline. I believe earlier this morning, Novartis announced that longer follow-up time is needed to determine the regulatory path forward for their BET inhibitor. Curious how that impacts at all your thinking or development strategy for your BET.

嘿。早安.感謝您回答我的問題。有一些正在籌備中。我相信今天早上早些時候，諾華宣布需要更長的追蹤時間來確定其 BET 抑制劑的監管路徑。很好奇這會如何影響您的 BET 思維或發展策略。

And then can you help us think about the potential development plans for povorcitinib and 262 in CSU? And just kind of where you see both molecules best fitting in the treatment paradigm? Thank you.

那麼您能幫我們思考一下povorcitinib和262在CSU的潛在開發計畫嗎？您認為這兩種分子最適合治療範例的地方是什麼？謝謝。

Yes. Good morning, Jess. This is Pablo. Let me take the first one. So our BET inhibitor, as we presented over the past year, and we will provide an update later this year, we're very happy with the data that we've seen so far. We've seen spleen reduction, spleen volume reduction. We've seen a pretty impressive improvement in symptoms, obviously, with the caveat that this is not a randomized blinded data, but very important effect on symptoms. We believe that the ability of our BET inhibitor to be dosed continuously as opposed to the way pelabresib has to be dosed with a break of a week, every two weeks, could potentially make it an important difference in our ability to control symptoms.

是的。早安，傑西。這是巴勃羅。讓我拿第一個。因此，我們的 BET 抑制劑，正如我們在過去一年中推出的那樣，我們將在今年稍後提供更新，我們對迄今為止看到的數據非常滿意。我們看到脾臟縮小，脾臟體積縮小。顯然，我們已經看到症狀有了相當令人印象深刻的改善，但需要注意的是，這不是隨機盲數據，而是對症狀的非常重要的影響。我們相信，我們的 BET 抑制劑能夠連續給藥，而不是 Pelabresib 必須每隔一周、每兩週給藥一次，這可能會對我們控制症狀的能力產生重要影響。

So our plan remains the same. As I said in my prepared remarks, we'll provide an update on the data before the end of the year, and we intend to advance into a Phase 3 study, and we will provide details on those designs when we provide an update on the data. So that plan remains the same.

所以我們的計劃保持不變。正如我在準備好的演講中所說，我們將在今年年底之前提供數據的更新，我們打算進入第三階段研究，當我們提供有關數據的更新時，我們將提供這些設計的詳細信息。所以這個計劃保持不變。

On [povo/262] for CSU, both are in different stages in a way. Povo, as you know, is in a randomized Phase 2 study for proof of concept. We believe there's a potential for povo in this indication because of the very strong anti-inflammatory effect that it has. So we look forward to sharing data and future plans after that.

在 CSU 的 [povo/262] 上，兩者在某種程度上處於不同的階段。如您所知，Povo 正在進行一項隨機第二階段研究以進行概念驗證。我們相信 povo 在這種適應症中具有潛力，因為它具有非常強烈的抗發炎作用。因此，我們期待在此之後分享數據和未來計劃。

262 is in a randomized Phase 2 study with two dose levels at 50 and 150 compared with placebo. And we also initiated a study or a lower dose of 25 milligrams compared with placebo. And the idea here is to explore a full range of doses for 262 to potentially once we have the results, assuming positive results to be ready for pivotal studies.

262 正在進行一項隨機 2 期研究，與安慰劑相比，有 50 和 150 兩個劑量水平。而且我們也啟動了一項研究，與安慰劑相比，劑量較低為 25 毫克。這裡的想法是，一旦我們得到結果，就可能探索 262 的全範圍劑量，假設積極的結果已為關鍵研究做好了準備。

In terms of how both fit, I think the difference here is probably a sequence on how these medicines could potentially be used in patients with SCAC. As you know, first line of therapy is antihistamines. About 50% to 60% of the patients do not respond into antihistamine or progress on antihistamines. This is a multiyear disease. And so patients need a sequence of treatment to be used to see which one controls best the symptoms for that particular individual.

就兩者如何匹配而言，我認為這裡的差異可能在於這些藥物如何可能用於 SCAC 患者的順序。如您所知，第一線治療是抗組織胺。大約 50% 至 60% 的患者對抗組織胺沒有反應或抗組織胺治療進展。這是一種多年性疾病。因此，患者需要進行一系列治療，以確定哪種治療能夠最好地控制特定個體的症狀。

The mechanism is different. Povorcitinib has a broad inflammatory effect. 262 is exquisitely designed to block MRGPRX2 in mast cells in the skin. So we believe that that selectivity will lead to an excellent safety profile. So once we have data for both programs, we'll share a little bit more on how we think those can potentially be sequenced in the treatment paradigm.

機制不同。Povorcitinib 具有廣泛的發炎作用。 262經過精心設計，可阻斷皮膚肥大細胞中的MRGPRX2。因此，我們相信這種選擇性將帶來優異的安全性。因此，一旦我們獲得了這兩個項目的數據，我們將分享更多關於我們認為如何在治療範式中對這些項目進行排序的資訊。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Good morning. Thank you for taking my questions. Just regarding the Escient portfolio, could you just help us understand how you're thinking about development strategy here when you think about the different mechanisms addressing some of these diseases and how you see the differentiation playing out? Thank you.

早安.感謝您回答我的問題。就 Escient 產品組合而言，當您考慮解決某些疾病的不同機制時，您能否幫助我們了解您如何考慮這裡的開發策略以及您如何看待差異化的發揮？謝謝。

Yeah. So we have two programs that were acquired with Escient: MRGPRX2 and MRGPX4. So MRGPRX2 is currently being developed in three indications -- chronic spontaneous urticaria. And I just highlighted where we are with that indication.

是的。因此，我們有兩個透過 Escient 獲得的程式：MRGPRX2 和 MRGPX4。因此，MRGPRX2 目前正在針對三種適應症進行開發中—慢性自發性蕁麻疹。我只是強調了我們目前的情況。

We have an ongoing study with two dose levels versus placebo, 50 and 150; and the second study of 25 milligrams versus placebo. Once we have all that data, we'll decide next steps for chronic spontaneous urticaria. For the other two indications are chronic inducible urticaria, particularly focused on two of those, dermographism and cold-induced urticaria and atopic dermatitis.

我們正在進行一項研究，使用兩種劑量水平與安慰劑比較：50 和 150；第二項研究是 25 毫克與安慰劑的比較。一旦我們掌握了所有這些數據，我們將決定慢性自發性蕁麻疹的下一步措施。其他兩種適應症是慢性誘發性蕁麻疹，特別關注其中兩種，皮膚划痕症、寒冷誘導性蕁麻疹和異位性皮膚炎。

The reason why we like MRGPRX2 as a target is the excellent selectivity, not just for cell type, mast cells, but also mast cells specifically in the skin and connective tissues. And we think that should lead to an excellent safety profile and make this, perhaps, in some of these patients, the first therapy after patients progress on antihistamines in the case of urticaria, chronic urticarias, for example. So good evidence of efficacy, together with a very, very clean safety, we think it will make this a very important option for patients at that stage of the disease.

我們之所以喜歡 MRGPRX2 作為標靶，是因為它具有出色的選擇性，不僅針對細胞類型、肥大細胞，而且還針對皮膚和結締組織中的肥大細胞。我們認為，這應該會帶來良好的安全性，並可能成為其中一些患者在蕁麻疹（例如慢性蕁麻疹）的抗組織胺治療進展後的第一種治療方法。如此良好的療效證據，加上非常非常乾淨的安全性，我們認為這將使其成為該疾病階段患者的一個非常重要的選擇。

The second program was MRGPRX4. This has been developed in patients with cholestatic pruritus, specifically primary biliary cirrhosis and primary sclerosing cholangitis. We know that X4 is a receptor. Bile acids and bile salts bind to it, and this is an important way in why these patients have intractable pruritus.

第二個程式是 MRGPRX4。這是在膽汁淤積性搔癢症患者中出現的，特別是原發性膽汁性肝硬化和原發性硬化性膽管炎患者。我們知道X4是一種受體。膽汁酸和膽鹽與其結合，這是這些患者出現頑固性搔癢的重要原因。

We are conducting a randomized double-blind study in those indications. We'll have data in the first quarter of 2025, same as for MRGPRX2 program. And once we report all the data early next year, we'll give you clarity on the next steps.

我們正在針對這些適應症進行一項隨機雙盲研究。我們將在 2025 年第一季獲得數據，與 MRGPRX2 計劃相同。一旦我們明年初報告所有數據，我們將向您明確接下來的步驟。

Eric Schmidt, Cantor Fitzgerald.

埃里克·施密特，康托·菲茨傑拉德。

Well, thanks for taking my question and congrats again on all the updates. Maybe a commercial question for Matteo on Opzelura and the potential upcoming launch for pediatric AD in the second half of next year. How do you think you're doing with regard to formulary access and efforts to ensure reimbursement and what could be a pretty sizable marketplace? Thanks.

好吧，感謝您提出我的問題，並再次祝賀所有更新。對於 Matteo 來說，也許是關於 Opzelura 的商業問題，以及明年下半年可能推出的兒科 AD 藥物。您認為您在處方准入和確保報銷方面做得如何，以及什麼可能是一個相當大的市場？謝謝。

Yes. Thanks, Eric, for the question. On the pediatric side, we're very excited about the potential for us to bring this new tool to patients 2 and 11 years old in AD. The unmet need is very clearly there. We have two million patients in terms of sizing. They're still cycling vastly on TCS and TCIs. And there still remain a high unmet need for us to potentially get into that.

是的。謝謝埃里克提出的問題。在兒科方面，我們對將這項新工具帶給 2 歲和 11 歲 AD 患者的潛力感到非常興奮。未滿足的需求是非常明顯的。就規模而言，我們有 200 萬名患者。他們仍然大量使用 TCS 和 TCI。我們仍然有很大的未滿足的潛在需求。

In terms of the 2025 formulary coverage, I mean, we look at the formulary position for the entire Opzelura brand for next year. Right now, from the feedback that we're receiving, we're confident that we will have a competitive overall coverage also for next year. And that will include, obviously, the pediatric indication if we had to come to fruition.

就 2025 年處方覆蓋範圍而言，我的意思是，我們著眼於明年整個 Opzelura 品牌的處方位置。目前，根據我們收到的回饋，我們有信心明年的整體覆蓋範圍也將具有競爭力。顯然，如果我們必須取得成果，這將包括兒科適應症。

Kelly Shi, Jefferies.

施凱莉，傑弗里斯。

Congrats on the call. Thanks for taking my questions. Curious for the Phase 3 trial ruxolitinib cream in the mild to moderate HS. What is the rationale for using (inaudible) and the primary endpoint on HiSCR75 over typically use the HiSCR50? Thank you.

恭喜您接到電話。感謝您回答我的問題。對 ruxolitinib 乳膏治療輕度至中度 HS 的 3 期試驗感到好奇。使用 HiSCR75 的基本原理（聽不清楚）和主要終點（相對於通常使用的 HiSCR50）是什麼？謝謝。

Kelly, it's Steven. Thanks for the question. So firstly, there's a lot of unmet need in mild to moderate HS defined in our study as people with abscess and nodules of account of about 3 to 10, no draining tunnels. And those patients can have a reasonable placebo effect because of the disease phenotype I just described to you.

凱莉，是史蒂文。謝謝你的提問。首先，我們的研究中將輕度至中度 HS 定義為患有膿瘍和結節約 3 至 10 個且沒有引流通道的患者，但仍有大量未滿足的需求。由於我剛才向您描述的疾病表型，這些患者可以獲得合理的安慰劑效應。

So that's -- looking at HiSCR75 will help to control for that. It's a higher end point, a higher bar, obviously, address the unmet need and hopefully eliminate a large placebo effect to get it across the finish line. It's agreed with regulatory agencies, and we're a go on the program. Thanks.

因此，查看 HiSCR75 將有助於控制這一點。顯然，這是一個更高的終點，更高的標準，解決未滿足的需求，並希望消除大的安慰劑效應，以使其跨越終點線。它已與監管機構達成一致，我們正在繼續該計劃。謝謝。

Matt Phipps, William Blair.

馬特·菲普斯，威廉·布萊爾。

I had another question on 262. The clinical trial recently showed the addition of 25 mg arm to that CSU trial. Can you give us any rationale for that? I assume that is maybe not going to be included in the Q1 update?

我在 262 上還有一個問題。最近的臨床試驗顯示，CSU 試驗中增加了 25 毫克組。您能給我們解釋一下嗎？我認為這可能不會包含在第一季更新中？

And also just thinking about the profile here, are you guys -- should we think most about I guess, competing with the recent BTK data as far as another oral? Or do you look at maybe some of the more effective treatments like the [KIN] inhibitors as far as efficacy goes?

而且只是想一下這裡的概況，你們是不是——我想我們應該考慮最多的是，與最近的 BTK 數據進行另一次口頭競爭？或者就療效而言，您是否會考慮一些更有效的治療方法，例如 [KIN] 抑制劑？

Yes, Matt, thank you for the question. So the reason for the 25 is to have -- to explore the full range of doses. So as you point out, there's an ongoing study, 50 versus 150 versus placebo. That's the data that we're going to have in the first quarter of 2025. We decided in the meantime to start a second study with 25 milligrams versus placebo in order to have the full range of doses explored. So if we have positive data in the ongoing study, then we'll be ready with the 25 already running to be -- to get to a Phase 3 study faster. So that's the idea of the 25-milligram, to explore the full range of dose of 262 in patients with CSU.

是的，馬特，謝謝你的提問。所以 25 的原因是要探索完整的劑量範圍。正如你所指出的，有一項正在進行的研究，分別是 50 人與 150 人與安慰劑。這是我們將在 2025 年第一季獲得的數據。同時，我們決定開始第二項研究，使用 25 毫克與安慰劑進行對比，以探索完整的劑量範圍。因此，如果我們在正在進行的研究中獲得積極的數據，那麼我們將準備好已經運行的 25 項研究，以便更快地進入第 3 階段研究。這就是 25 毫克的想法，探索 262 在 CSU 患者中的完整劑量範圍。

In terms of worry fits, I mentioned a few times before that we don't necessarily expect to send the same level of efficacy that you may have with the Kidd antibody. When you deplete all mast cells, which is what Kidd antibodies do, obviously, the efficacy is very strong. In our opinion, that comes with a series of side effects that have been well reported.

就擔憂而言，我之前曾多次提到過，我們不一定期望提供與基德抗體相同水平的功效。當你耗盡所有肥大細胞時，這就是基德抗體的作用，顯然，功效非常強大。我們認為，這會帶來一系列已充分通報的副作用。

I think with BTK inhibitor, it is a little bit cleaner in terms of safety profile. We think 262, if it shows positive data in CSU, will fit perfectly after antihistamines. Once patients progress in antihistamines, what we expect to be a very clean safety profile for a very convenient daily pill will be ideal for those patients before they need to try more aggressive alternatives. So that we continue to believe is a perfect fit for 262 in CSU.

我認為使用 BTK 抑制劑，在安全性方面會更乾淨一些。我們認為，如果 262 在 CSU 中顯示陽性數據，那麼在抗組織胺之後將非常適合。一旦患者在抗組織胺方面取得進展，我們期望一種非常方便的每日藥丸的非常乾淨的安全性，對於這些患者來說將是理想的選擇，然後他們需要嘗試更積極的替代方案。因此我們仍然相信 262 非常適合 CSU。

James Shin, Deutsche Bank.

詹姆斯‧辛，德意志銀行。

Hi, thanks for taking our question. For ruxolitinib creams HS Phase 3, what time point is the HiSCR75 being assessed? When I look at the pipeline slide, it shows the approval range starting around mid '27 time frame. So is Phase 3 HS data for rux cream expected in '26?

您好，感謝您提出我們的問題。對於 ruxolitinib 乳膏 HS 3 期，評估 HiSCR75 的時間點是什麼？當我查看管道幻燈片時，它顯示批准範圍從 27 年中期左右開始。那麼，rux 霜的 3 期 HS 數據預計會在 26 年發布嗎？

Yeah, it's Steven. It's hard to be given much precision beyond what we showed in that for the moment because of the study has to start and be underway and then see how it enrolls. The endpoint is HiSCR75 as agreed with regulatory agencies. And we'll update at a more appropriate time and try to give more precision on the endpoint. We expect, given the unmet need, the lack of competition in the space and the excitement around this, that it should enroll well, but we'll see how it goes at a later time. Thanks.

是的，這是史蒂文。除了我們目前所展示的內容之外，很難給出更多的精確度，因為研究必須開始並正在進行，然後看看它是如何註冊的。終點是與監管機構商定的 HiSCR75。我們將在更合適的時間進行更新，並嘗試在端點上提供更高的精確度。考慮到未滿足的需求、該領域缺乏競爭以及圍繞這一點的興奮，我們預計它應該會很好地註冊，但我們稍後會看到它的進展。謝謝。

Vikram Purohit, Morgan Stanley.

維克拉姆‧普羅希特，摩根士丹利。

Hi, good morning. Thank you for taking our question. So we had one on the oncology pipeline. For the Phase 1 data sets expected for the mutant CALR program and then also for the JAK2V617 programs in 2025, could you help us understand just the scope of those data releases that we could expect to see and how you'll be gauging success for these initial data sets?

嗨，早安。感謝您提出我們的問題。所以我們在腫瘤學管道上有一個。對於突變 CALR 計劃以及 2025 年 JAK2V617 計劃預期的第一階段資料集，您能否幫助我們了解我們預計會看到的這些資料發布的範圍以及您將如何衡量這些資料的成功與否初始資料集？

And if I could squeeze a question in on the base business. For Opzelura, could you just give us a sense of how utilization is tracking in terms of tubes per patient per year for both AD and vitiligo versus your last update? Thank you.

我是否可以問一個有關基本業務的問題。對於 Opzelura，您能否讓我們了解一下與您上次更新相比，每年每位患者的 AD 和白斑風管使用情況追蹤情況如何？謝謝。

Let me take the first one on the pipeline. So the mutant CALR antibody program is ahead of 617F. As we disclosed previously, the 617F program this year started in healthy volunteers to understand the formulation better. And then we advanced it into in myelofibrosis patients, and it's now in patients, but it's a little bit behind mutant CALR antibody. We expect both to have meaningful data available next year, but that data will be comprised as basically a fairly large number of patients with single agent, particularly for the mutant CALR antibody and some of the data also in combination.

讓我來談談管道中的第一個。所以突變CALR抗體方案領先617F。正如我們之前所披露的，今年的 617F 計劃在健康志願者中啟動，以更好地了解配方。然後我們將其推進到骨髓纖維化患者中，現在已經在患者中進行，但它比突變 CALR 抗體稍微落後。我們預計明年將獲得有意義的數據，但這些數據基本上將包含相當多的使用單一藥物的患者，特別是突變 CALR 抗體，並且一些數據也是組合的。

I think it's difficult to start putting numbers around what success looks like. What we've been consistent about is that what we expect to see in addition to obviously addressing some of the signs and symptoms of myeloproliferative neoplasms is to see some evidence of decrease in VAF or allele reduction with these medicines. And we expect that we will have that data next year when we decide the right timing to disclose to provide an update.

我認為很難開始用數字來說明成功是什麼樣子。我們一直認為，除了明顯解決骨髓增生性腫瘤的一些徵兆和症狀之外，我們期望看到這些藥物減少 VAF 或等位基因減少的一些證據。我們預計明年當我們決定披露並提供更新的正確時機時，我們將獲得這些數據。

On Opzelura utilization, for AD, we still see over two tubes per patient per year. For vitiligo, we're beefing up the cohort we're following throughout the time to make sure that the cohort is meaningful enough and as well as we follow long enough to a very reliable number.

在使用 Opzelura 治療 AD 時，我們每年仍然看到每位患者超過兩根管子。對於白斑，我們正在加強我們一直追蹤的隊列，以確保該隊列足夠有意義，並且我們追蹤足夠長的時間以獲得非常可靠的數字。

What you see on the prescription side is that the growth rate is actually coming from new patients as well as refill. So we continue to improve over time. At the same time, we're increasing the focus on the overall adherence, and we have quite exciting programs kicking off this quarter and the first quarter of next year to actually put more emphasis on this part of support for our patient population.

您在處方方面看到的是，成長率實際上來自新患者以及補充患者。因此，我們會隨著時間的推移而不斷改進。同時，我們越來越關注整體依從性，並且我們在本季度和明年第一季啟動了非常令人興奮的計劃，以實際上更加重視對我們患者群體的這部分支持。

Derek Archila, Wells Fargo.

德里克·阿奇拉，富國銀行。

Hey, good morning and congrats on the quarter. Just two quick ones. Just on 262. I just want to know if you've characterized the tryptase reduction you've seen with the agent in the earlier-stage trials. And then just on the base business, just in terms of what we've seen with Jakafi in the MF market, it looks like you're still driving new patient volumes. Just was wondering if that's more share gains or just the overall market growing? Thanks.

嘿，早上好，恭喜本季。就兩個快的。就在262。我只是想知道您是否描述了在早期試驗中使用該藥物所看到的類胰蛋白酶減少的特徵。然後就基礎業務而言，就我們在 MF 市場上看到的 Jakafi 而言，看起來您仍在推動新的患者數量。只是想知道這是否是更多的份額收益或只是整體市場的成長？謝謝。

Let me take the first one on 262. So we are measuring tryptase in the ongoing trials. A word of caution, I think that the degree of the magnitude of tryptase reduction that we expect to see is not the same you'll see with depletion of mast cells by using a [KIN] antibody. I mean, it's just in the sense that if you deplete mast cells regardless of their location, you're going to have -- particularly those in circulation, you're going to have pretty dramatic risk in tryptase in circulation.

讓我拿262上的第一個。因此，我們正在正在進行的試驗中測量類胰蛋白酶。需要注意的是，我認為我們預期看到的類胰蛋白酶減少程度與使用 [KIN] 抗體消除肥大細胞時看到的程度不同。我的意思是，這只是在某種意義上，如果你耗盡肥大細胞，無論其位置如何，你都會——特別是那些循環中的細胞，循環中的類胰蛋白酶會面臨相當大的風險。

What we address with 262 is MRGPRX2 in the mast cells in the skin. As a result of which, the decrease in tryptase that we may see, it's not going to be quite as dramatic. But we are measuring that and we will report it.

我們用 262 解決的是皮膚肥大細胞中的 MRGPRX2。因此，我們可能會看到類胰蛋白酶的減少，但不會那麼劇烈。但我們正在衡量這一點，我們會報告它。

Thanks, Derek. Yeah, as far as the myelofibrosis market goes, Jakafi, as we said, continues to grow. Total patients increased 4% in myelofibrosis. But in fact, yes, the overall market is growing. Patients are getting first line. They're starting earlier because now, you have multiple agents to go to after Jakafi and patients are being treated in the second line, third line and even fourth-line setting, which we had not seen before.

謝謝，德里克。是的，就骨髓纖維化市場而言，正如我們所說，Jakafi 正在繼續成長。骨髓纖維化患者總數增加了 4%。但事實上，是的，整個市場正在成長。患者正在第一線接受治療。他們開始得更早，因為現在，在賈卡菲之後，你需要去找多個代理人，患者正在二線、三線甚至四線環境中接受治療，這是我們以前從未見過的。

David Lebowitz, Citibank.

大衛‧勒博維茨，花旗銀行。

Thank you for taking my question. Just following up on the Jakafi question. I understand that the step down in the catastrophic out-of-pocket costs are in the middle. They'll be at their lowest $2,000 per year next year. Has that played any role in the uptick in Jakafi growth in the current quarter? And then looking forward to later in the year, could you outline what type of data we might actually see at ASH?

感謝您回答我的問題。只是跟進賈卡菲的問題。據我所知，災難性自付費用的下降是在中間。明年他們的年薪將降至最低的 2,000 美元。這對本季度 Jakafi 成長的上升起到了任何作用嗎？然後展望今年晚些時候，您能否概述一下我們可能在 ASH 上實際看到的資料類型？

So I'll take the first question and hand it over to Steven or Pablo. So yeah, so Jakafi -- well, what we always believe that Medicare Part D patients who are cancer patients, out-of-pockets should really not be a barrier to use. So really getting rid of the catastrophic coverage this year for patients on Medicare Part D was a very good thing. Going to $2,000 out of pocket next year is a very good thing and especially smoothing over the whole period of time. So patients out of pocket in any given month is better.

所以我將回答第一個問題並將其交給史蒂文或巴勃羅。所以，是的，Jakafi——嗯，我們一直認為，醫療保險 D 部分的癌症患者自付費用確實不應該成為使用的障礙。因此，今年真正取消 Medicare D 部分患者的災難性保險是一件非常好的事情。明年自掏腰包達到 2,000 美元是一件非常好的事情，而且在整個時期內特別平穩。因此，患者在任何特定月份自掏腰包都比較好。

But really, the growth that we see is coming from demand. And mostly as we've said, from polycythemia vera, and mostly, that's because physicians are starting patients earlier on Jakafi and polycythemia vera because of the results largely from MAJIC-PV, which demonstrates that patients will have thrombosis-free survival improvements when they start Jakafi and when they start Jakafi earlier. Steve?

但實際上，我們看到的成長來自需求。正如我們所說，主要是來自真性紅血球增多症，而且主要是因為醫生更早開始對患者使用Jakafi 和真性紅血球增多症，因為主要來自MAJIC-PV 的結果，這表明患者在接受治療時將獲得無血栓生存期的改善啟動 Jakafi 以及當他們更早啟動 Jakafi 時。史蒂夫？

Yeah, David, it's Steven. Unfortunately, it's premature to comment on what will be seen at ASH. We have to wait for the acceptances, and then we will provide the update at that point.

是的，大衛，是史蒂文。不幸的是，現在對 ASH 上的情況發表評論還為時過早。我們必須等待接受，然後我們將提供更新。

Marc Frahm, TD Cowen.

馬克·弗拉姆，TD·考恩。

Hi. Yes, thanks for taking my questions. Just on 262, back to adding the 25-milligram dose, can you just talk about kind of what led to adding that? And was it informed at all by the AD trial, which I believe this market has completed as of over the summer.

你好。是的，感謝您回答我的問題。就在 262 上，回到添加 25 毫克劑量的問題，您能談談導致添加該劑量的原因嗎？AD 試驗是否告知了這一點，我相信這個市場已經在今年夏天完成了。

And then just when you get the data from those different dose levels in CSU, you obviously, you don't necessarily need to match the Kidd antibodies from an efficacy perspective given the potential for improved safety here. But what is that kind of minimum bar that would justify use of a branded drug after antihistamines in your mind?

然後，當您從 CSU 中的不同劑量水平獲得數據時，顯然，您不一定需要從功效角度匹配基德抗體，因為這裡有提高安全性的潛力。但在您看來，在抗組織胺之後使用品牌藥物的最低標準是多少呢？

Yeah. So let me -- first of all, the decision to start whether it is indeed a new study or it's part of the ongoing study, but it really is a totally separate cohort with 25 milligrams versus placebo, they had nothing to do with any data that we've seen from the program. We made that decision early in the process very soon after the transaction closed, and it was based on our desire to be ready for a Phase 3 study as soon as possible once we have data. That decision was made at that time.

是的。首先，讓我決定開始這是否確實是一項新研究，還是正在進行的研究的一部分，但這確實是一個完全獨立的隊列，其中 25 毫克與安慰劑相比，它們與任何數據無關我們從節目中看到的。我們在交易結束後不久就做出了這一決定，這是基於我們希望在獲得數據後儘快為第三階段研究做好準備的願望。這個決定就是在那個時候做出的。

In terms of the bar, look, all the patients in the ongoing study are refractory to antihistamines. So basically, after that, the question is what's the best option for these patients? We believe in that context, obviously, showing efficacy over placebo and with what we believe will be an excellent safety profile will be sufficient for 262 to be the first option after antihistamines in some of the patients with CSU. We remain convinced that, that is the right place for this drug to be used, assuming obviously efficacy in the randomized trial.

就標準而言，你看，正在進行的研究中的所有患者都對抗組織胺抗藥性。所以基本上，之後的問題是這些患者的最佳選擇是什麼？我們相信，在這種情況下，顯然，262 表現出優於安慰劑的療效，並且具有出色的安全性，足以使 262 成為一些 CSU 患者繼抗組織胺藥物之後的首選。我們仍然相信，這是該藥物使用的正確場所，假設在隨機試驗中具有明顯的療效。

Brian Abrahams, RBC Capital Markets.

布萊恩‧亞伯拉罕斯 (Brian Abrahams)，加拿大皇家銀行資本市場部。

Hey, good morning. Thanks for taking my question and congrats on the quarter and all the progress. Maybe on the CDK2, I'm curious if there's any updates on the aspects that you're considering as you think about the next steps and pivotal plans into the upcoming FDA meeting and sort of how you're thinking about the balance between exploring late line versus maintenance? And then any more color around the companion diagnostic for that drug? Thanks.

嘿，早安。感謝您提出我的問題，並祝賀本季和所有進展。也許在 CDK2 上，我很好奇您在考慮即將舉行的 FDA 會議的後續步驟和關鍵計劃時正在考慮的方面是否有任何更新，以及您如何考慮後期探索之間的平衡線路與維護？那麼該藥物的伴隨診斷還有更多顏色嗎？謝謝。

Yes, Brian, it's Steven. Thanks for the question. So as Pablo said in his slides, there are numerous areas we're interested in. But broadly speaking, the ovarian cancer settings divided into a platinum refractory and a platinum-sensitive setting divided by a time period of approximately six months, although that's getting gray in terms of retreatment. And there are different unmet needs in each population, and we're interested in both.

是的，布萊恩，是史蒂文。謝謝你的提問。正如巴勃羅在他的幻燈片中所說，我們感興趣的領域有很多。但從廣義上講，卵巢癌設置分為鉑類難治性和鉑類敏感性設置，劃分時間約為六個月，儘管在再治療方面，這種情況正在變得灰色。每個人群都有不同的未滿足的需求，我們對兩者都感興趣。

You saw the data update at ESMO. We got upwards of north of a 30% response rate, but the data is still maturing and there may actually be late responders where it may go up. So we really like the profile we've seen. We've done 200-plus patients of dose range in work. So we think we're in a very good place to pick both a dose and schedule.

您看到了 ESMO 的資料更新。我們的回覆率超過了 30%，但數據仍在成熟，實際上可能有較晚的回覆者，回覆率可能會上升。所以我們真的很喜歡我們所看到的個人資料。我們已經對超過 200 名劑量範圍內的患者進行了治療。所以我們認為我們在選擇劑量和時間表方面處於一個非常好的位置。

In the platinum refractory ovarian cancer setting, there are potentially two ways of thinking about it. For the US, primarily the FDA, one could do a single-arm study in that setting, looking at response rate and durability of response to get it across the finish line. As potential confirmatory study and for ex-US approvals, that will require a randomized study in that setting. And as it was on the slide deck, that would be against investigator choice chemotherapy of which their numbers, their single-agent paclitaxel, topotecan, liposomal doxorubicin, et cetera, with a time to event endpoint, like progression-free survival. And we like the profile of the drug there.

在鉑類難治性卵巢癌的治療中，可能有兩種思考方式。對於美國，主要是 FDA，可以在這種情況下進行單臂研究，觀察反應率和反應的持久性，以使其衝過終點線。作為潛在的驗證性研究和美國以外的批准，這將需要在該環境中進行隨機研究。如幻燈片上所示，這將反對研究者選擇化療，其中包括單藥紫杉醇、托泊替康、脂質體多柔比星等，以及達到事件終點的時間，例如無惡化存活期。我們喜歡該藥物的概況。

The other setting that's of extreme interest to us, and we spoke about it at ESMO quite a lot, is the platinum-sensitive ovarian cancer setting, particularly where bevacizumab maintenance is used. And the disease gets a little complicated here because you look at HRD-proficient and HR-deficient patients in terms of use of PARP inhibitors. But if you just focus on the majority population there, the HR-deficient patients, the majority of those are Cyclin E1 positive. We're doing safety work now with CDK2 and bev maintenance, and that's an enormous interest to us. There's need there.

我們非常感興趣的另一個環境是鉑敏感卵巢癌環境，特別是使用貝伐珠單抗維持治療的情況，我們在 ESMO 上對此進行了很多討論。這裡的疾病變得有點複雜，因為你會根據 PARP 抑制劑的使用來觀察 HRD 熟練和 HR 缺乏的患者。但如果你只關注那裡的大多數人群，HR 缺陷患者，其中大多數都是 Cyclin E1 陽性。我們現在正在做 CDK2 和 bev 維護的安全工作，這對我們來說是一個巨大的興趣。那裡有需要。

We can potentially improve cure rates, and it would be a pretty simple construct in terms of design. It will be bev maintenance plus placebo versus bev maintenance plus CDK2, and we're doing the enabling work for that now. That is obviously a longer study and we'll deliver later. But we like the profile of the drug there that we've seen so far in terms of its therapeutic ratio. So those are the areas of interest in terms of study designs.

我們有可能提高治癒率，而且從設計角度來看，這將是一個非常簡單的結構。這將是 bev 維護加安慰劑與 bev 維護加 CDK2 的對比，我們現在正在為此進行支援工作。這顯然是一項更長的研究，我們將稍後提供。但我們喜歡迄今為止我們所看到的該藥物的治療比例。因此，這些是研究設計方面感興趣的領域。

On the companion diagnostic, we haven't given details per se on what our cutoff is, but there's two ways of looking again at this population. You can look at the gene in terms of amplification, the CCNE1 gene, and others are doing that. Or you can look at protein of expression by IHC, Cyclin E1 expression, and that's where we focused. And that is a much bigger population. Without cutoff, it's probably more than half of ovarian cancer right now.

關於伴隨診斷，我們沒有給出有關我們的截止值本身的詳細信息，但有兩種方法可以重新審視這個人群。你可以從擴增的角度來看這個基因，CCNE1基因，其他人也在這麼做。或者您可以透過 IHC、細胞週期蛋白 E1 表達來查看蛋白質表達，這就是我們關注的重點。這是一個更大的人口。如果不切斷的話，目前可能有一半以上是卵巢癌。

But we need to have more discussions with regulators and CDH on our companion diagnostic and the cutoff we use in. But the data we showed at ESMO was using our assay with the cutoff that we've determined internally. Thanks.

但我們需要與監管機構和 CDH 就我們的伴隨診斷和我們使用的臨界值進行更多討論。但我們在 ESMO 上展示的數據是使用我們的檢測方法以及我們內部確定的截止值。謝謝。

Andrew Berens, Leerink Partners.

安德魯貝倫斯，Leerink Partners。

Hi. This is (inaudible) on for Andy. So with the upcoming HS straight out for povo, just one question, looking ahead to the commercial dynamics. So the efficacy look strong relative to other agents being developed for HS even though it's oral. I was wondering how you see the safety of povo and if the JAK class concerns are reflected on the label, how might that impact the drug commercially. I guess I'm asking if you anticipate a black box like other JAK agents? Thanks.

你好。這是安迪的（聽不清楚）。因此，隨著即將推出的 HS 直接面向 povo，只有一個問題，展望商業動態。因此，儘管它是口服藥物，但與正在開發的其​​他治療 HS 的藥物相比，其療效看起來更強。我想知道您如何看待 povo 的安全性，以及如果 JAK 類問題反映在標籤上，這會對藥物的商業產生什麼影響。我想我是在問你是否會像其他 JAK 特工一樣預見黑盒子？謝謝。

Yeah, it's Steven, I'll address that. I mean, we've spoken a bit about how well the studies are going. The Phase 2 profile we saw with the HiSCR100upwards of 29%. And in fact, enrollment is going very well. It is an inflammatory disease. So there is a reasonable chance or more than a reasonable chance that it will have class effect labeling in terms of a black box. So we do expect that to be the case going forward.

是的，我是史蒂文，我會解決這個問題。我的意思是，我們已經討論過研究的進展。我們在 HiSCR100 中看到的第 2 階段曲線高達 29%。事實上，招生進展非常順利。這是一種發炎性疾病。因此，有合理的機會或超過合理的機會，它會以黑盒子的形式產生階級效應標籤。因此，我們確實預期未來會出現這種情況。

If you look at the profile of a JAK-STAT inhibitor versus a biologic, which will only attack, by definition, one pathway, for example, IL-17, here, we can have more broad coverage of different interleukins. And then potentially that would result in better disease control as we saw in the Phase 2 data, and that's the data set we'd like to replicate. Thanks.

如果您查看 JAK-STAT 抑制劑與生物製劑的概況，根據定義，生物製劑只會攻擊一種途徑，例如 IL-17，在這裡，我們可以更廣泛地覆蓋不同的白細胞介素。正如我們在第二階段數據中看到的那樣，這可能會帶來更好的疾病控制，這就是我們想要複製的數據集。謝謝。

Andy Chen, Wolfe Research.

安迪陳，沃爾夫研究中心。

Hey, good morning. Thank you for taking the question. I'm curious if you can remind us the size of your sales force and how it's split across heme and derm and others. I'm trying to figure out if your SG&A would trend up as you get your topical into pediatric AD, into PN, and also your JAK inhibitor. Are you going to double down on the derm sales force? Or are you going to capitalize on the existing synergies? Thank you.

嘿，早安。感謝您提出問題。我很好奇您能否提醒我們您的銷售隊伍的規模以及其在血紅素、皮膚和其他領域的分佈。我試圖弄清楚，當您將外用藥物納入兒科 AD、PN 以及 JAK 抑制劑時，您的 SG&A 是否會呈上升趨勢。您打算加倍投入真皮銷售團隊嗎？或者您打算利用現有的綜效嗎？謝謝。

So I guess in the US, Matteo can speak about that. I mean, the big picture is that we have established around the world, in fact, now in most of the European countries, in the US and in Canada, we have a dermatology IAI teams that are in place and are sized in a way where we anticipate that they will be able to be -- to do most of the work required for the launches of the new indication, absolutely clearly for Opzelura.

所以我想在美國，馬特奧可以談論這一點。我的意思是，大局是我們已經在世界各地建立了，事實上，現在在大多數歐洲國家、美國和加拿大，我們都有一個皮膚科 IAI 團隊，這些團隊已經就位，規模也適合我們預期他們將能夠完成推出新適應症所需的大部分工作，這對Opzelura 來說絕對是顯而易見的。

And when povo comes up, it may be a marginal increase, but nothing that is very, very high. I mean, how many people do you have now in the US, Matteo?

當 povo 出現時，可能會略有增加，但不會非常非常高。我的意思是，馬特奧，你現在在美國有多少人？

The full footprint across all teams is around a couple of hundred people. It's -- we see it in line with other competitors. We also saw competitors staffing up a full field force dedicated to HS. We look forward to see the Phase 3 data next year. But from what it looks like now, it's going to be a mix of exactly staffing up (inaudible) while capturing synergy with the current footprint we have.

所有團隊的總規模約為數百人。我們認為它與其他競爭對手是一致的。我們還看到競爭對手配備了專門負責 HS 的完整現場人員。我們期待明年看到第三階段的數據。但從現在的情況來看，這將是一個精確的人員配備（聽不清楚）的組合，同時與我們現有的足跡實現協同作用。

Jay Olson, Oppenheimer.

傑·奧爾森，奧本海默。

Hey, congrats on the quarter and thank you for taking the question. Since you have a number of catalysts in the near term that could reshape the future top-line growth, can you talk about which one or two catalysts are most important and are there any gaps in your portfolio? And how are you thinking about business development strategy over the next year? Thank you.

嘿，恭喜本季度，感謝您提出問題。由於您在短期內有許多可以重塑未來收入成長的催化劑，您能否談談哪一兩個催化劑是最重要的以及您的投資組合中是否存在差距？您對明年的業務發展策略有何看法？謝謝。

Yeah, Maybe I'll take that. I mean, so if you go to the slide, we just presented in the slide 10, I mean it's basically saying what has happened recently is the probabilization of the increase in probability of success for (inaudible) Niktimvo is approved in third line and retifanlimab in SCAC. And as I said in my presentation, we -- collectively, if you put them together, you end up with something that would be around $800 million.

是的，也許我會接受。我的意思是，如果你看幻燈片，我們剛剛在幻燈片10 中展示，我的意思是，這基本上是說最近發生的事情是（聽不清）Niktimvo 被批准進入第三線和retifanlimab 的成功機率增加的可能性在SCAC。正如我在演講中所說，我們——總的來說，如果你把它們放在一起，你最終會得到大約 8 億美元的東西。

So each of them are relatively modest, if you wanted to classify them. But when you put them together, this is a meaningful contribution to the top line by 2030. What we have coming soon is povo, CDK2, ruxolitinib XR, and tafasitamab in first-line DLBCL. So that's, again, the number of projects that have been -- where the probability of success has increased with recent events.

所以如果你想對它們進行分類的話，它們中的每一個都相對溫和。但當你把它們放在一起時，你會發現這對 2030 年的收入來說是一個有意義的貢獻。我們即將推出用於第一線 DLBCL 的 povo、CDK2、ruxolitinib XR 和 tafasitamab。這又是已經完成的項目的數量——隨著最近發生的事件，成功的可能性增加。

I mean, for CDK2, clearly, the data is good. For povorcitinib, the Phase 2 data that we have accumulated is showing very good level of efficacy. And in fact, the follicular lymphoma data for tafa, which is the first of the CD19, CD20 combination, is in some way improving our chances of success in the first-line setting, where we are also doing CD19, CD20 combination. So that's the second step.

我的意思是，對於 CDK2，顯然數據很好。對於povorcitinib，我們累積的2期數據顯示出非常好的療效水準。事實上，tafa 的濾泡性淋巴瘤數據是第一個 CD19、CD20 組合，在某種程度上提高了我們在一線環境中的成功機會，我們也在一線環境中進行 CD19、CD20 組合。這是第二步。

And then we go into m-CALR, X2, 617F, TGF beta, PD-1, all the early pipeline that is moving very well. So what it does to us in terms of business development is really looking at maybe early technology type of deals where there are always things we can acquire, learn from, that we would be interested in. Or in the very hypothetical situation where we would find some of that, some very late stage like commercial products, that would be also of quality that we would ask for, which is not very common in oncology and dermatology and are very expensive.

然後我們進入 m-CALR、X2、617F、TGF beta、PD-1，所有早期管道都進展順利。因此，它在業務發展方面對我們的作用實際上是在關注早期技術類型的交易，其中總有我們可以獲得、學習的、我們感興趣的東西。或者在非常假設的情況下，我們會發現其中一些，一些非常後期的產品，例如商業產品，它們也具有我們所要求的質量，這在腫瘤學和皮膚病學中並不常見，而且非常昂貴。

So in some way, we are in a position today where our internal pipeline plus the acquisitions that we have done or the BD we have done recently is giving us a portfolio that works very well for what we need to compensate the Jakafi patent exploration around 2029. And we are not looking in the very short term at acquiring new assets that would require a lot of R&D expenses. And that's why we look at either early or very late with contribution to the top line that will come very quickly.

因此，在某種程度上，我們今天所處的位置是，我們的內部管道加上我們已經完成的收購或我們最近完成的BD 為我們提供了一個非常適合我們在2029 年左右補償Jakafi 專利探索所需的產品組合。我們不會在短期內考慮收購需要大量研發費用的新資產。這就是為什麼我們會儘早或很晚地考慮對很快就會實現的營收貢獻。

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

Hey, guys. Thanks for taking the question. Also had one on 262 in CSU. I'm just wondering how many patients are [Xolair-naive] versus experienced in the study? And if you think there could be any potential subgroups with greater efficacy, such as IgE low patients? Thank you.

嘿，夥計們。感謝您提出問題。在 CSU 的 262 上也有一場。我只是想知道在這項研究中，有多少患者是[Xolair-naive]和有經驗的患者？如果您認為可能有任何潛在的亞群具有更高的療效，例如 IgE 低的患者？謝謝。

So thank you for the question. So we're not going to provide any details on prior therapy in the study other than to say that all patients have refractory to antihistamines. In terms of the potential for certain subsets to have better efficacy, I'd rather not speculate at this point in time. Obviously, it's a very different mechanism for Xolair, which is, as you know, an anti-IgE antibody as opposed to 262. They work in a different pathway, but I'd rather not speculate at this point into the -- about the results, the future results of the study.

謝謝你的提問。因此，我們不會提供有關研究中先前治療的任何細節，只是說所有患者都對抗組織胺抗藥性。就某些子集具有更好功效的潛力而言，我現在不想推測。顯然，這對 Xolair 來說是一種非常不同的機制，正如您所知，Xolair 是一種抗 IgE 抗體，而不是 262。他們以不同的方式發揮作用，但我現在不想推測研究的未來結果。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO 資本市場。

Hi guys. Thank you so much for taking my questions. I'm just thinking about the ALK program readout in 4Q. I know you don't want to speculate too much, but maybe comment on kind of your confidence in the readout. It feels like this program has a few ups and downs despite the mechanistic rationale. Can you maybe highlight what gives you the confidence in the update and really in the program overall going forward? Thank you.

嗨，大家好。非常感謝您回答我的問題。我只是在考慮第四季度的 ALK 程序讀數。我知道您不想猜測太多，但也許可以評論一下您對讀數的信心。儘管有機械原理，但感覺這個程序還是有一些起伏。您能否強調一下是什麼讓您對更新以及整個計劃的未來充滿信心？謝謝。

Yeah, Evan, it's Steven. As we've been alluding to over the last year, we've sort of have to go to higher and higher doses to try and achieve the desired effect of the program, which just to remind you, would work potentially through inhibiting hepcidin and then relieving that break so that iron gets released and patients' hemoglobin improves from the underlying disease and then potentially from drug-induced disease.

是的，埃文，是史蒂文。正如我們去年提到的那樣，我們必須使用越來越高的劑量來嘗試達到該計劃的預期效果，這只是提醒您，可能會通過抑制鐵調素發揮作用，然後緩解這種破壞，使鐵釋放出來，患者的血紅蛋白從潛在的疾病中得到改善，然後可能從藥物引起的疾病中得到改善。

And I think it's safe to say at this point in time, we haven't seen to date yet sufficient efficacy to trigger a go on a future registration program. We'll update more data at the end of the year at an appropriate meeting and give you more color on that. Just to remind you, though, we do have an ongoing program in FOP that continues to enroll with ALK2. Thanks.

我認為目前可以肯定地說，迄今為止我們還沒有看到足夠的功效來觸發未來的註冊計劃。我們將在今年年底的適當會議上更新更多數據，並為您提供更多資訊。不過，請謹提醒您，我們確實在 FOP 中有一個正在進行的計劃，該計劃將繼續註冊 ALK2。謝謝。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi, thanks for taking my question. As you think about the HS opportunity, can you clarify for us how you think it would be different for rux cream versus povo? And also, do you have a sense -- I know it's still a little bit early, but in terms of usage of tubes for rux cream in HS, how do you think that will compare relative to what you have seen so far for AD and vitiligo? Thanks.

您好，感謝您提出我的問題。當您考慮 HS 機會時，您能否向我們澄清您認為 rux 奶油與 povo 有何不同？而且，你有沒有感覺——我知道現在還為時過早，但就 HS 中 rux 霜管的使用而言，你認為這與你迄今為止所看到的 AD 和白斑？謝謝。

So it's Steven. On your first question. So there's a spectrum of disease that goes mild, moderate and severe in HS. They're called Hurley stages, classifications by the number of abscesses and nodules, the number of draining tunnels and fistulas. Just to address the mild to moderate for which the cream is targeting, as I said earlier, the abscess nodule count is limited to less than 10.

所以是史蒂文.關於你的第一個問題。因此，熱射病的疾病範圍分為輕度、中度和重度。它們被稱為赫爾利階段，根據膿瘍和結節的數量、引流隧道和瘻管的數量進行分類。正如我之前所說，為了解決乳膏針對的輕度至中度膿瘍結節計數限制在 10 個以下。

To get on to our particular study, you have to have 3 to 10 abscess nodule count. There are no draining tunnels or fistulas in the mild to moderate population and the HiSCR75 will be the endpoint. And they're approximately up to between 100,000 and 150,000 patients with this with a lot of unmet need.

要繼續我們的特定研究，您必須有 3 到 10 個膿腫結節計數。輕度至中度人群中沒有引流隧道或瘻管，HiSCR75 將是終點。約有 10 萬至 15 萬名患者患有此病，但仍有大量需求未被滿足。

These patients tend to be underdiagnosed in the setting and tend to have disease for a long time before getting appropriately diagnosed and seeking treatment, and it may need chronic treatment. It's hard to determine now until we conduct the study and get the readout to exactly how long that would be.

這些患者在環境中往往未被充分診斷​​，並且在得到適當診斷和尋求治療之前往往已經患病很長時間，並且可能需要長期治療。現在很難確定，直到我們進行研究並讀出具體需要多長時間。

In terms of povorcitinib, it's looking at the right spectrum of the disease. So the moderate severe population with higher abscess nodule counts with the presence of fistulas and draining tunnels. And then the endpoints can go towards potentially, as Pablo said in his prepared remarks, complete resolution of everything -- abscess and nodules and removal of the draining tunnels and fistulas, which will be called a HiSCR100, obviously addresses a huge unmet need and takes care of a lot of morbidity. And again, chronicity of treatment and how many tubes will be needed will come from the Phase 3 study readout, but it will tend to be long therapy, if you want to just ballpark it at the moment. Thanks.

就 povorcitinib 而言，它正在研究該疾病的正確譜系。因此，膿瘍結節較高的中重度族群存在瘻管和引流通道。然後，正如巴勃羅在他準備好的發言中所說，終點可能會走向徹底解決一切問題——膿腫和結節，以及切除引流隧道和瘻管，這將被稱為HiSCR100，顯然解決了巨大的未滿足的需求，並需要照顧許多發病率。再說一遍，治療的長期性以及需要多少根管子將來自第三階段研究的讀數，但如果你想現在就大致了解一下，它往往會是長期治療。謝謝。

Kripa Devarakonda, Truist Securities.

Kripa Devarakonda，Truist 證券公司。

Hey, guys. Thank you so much for taking my question and congrats back on the quarter. I had a question about the CDK2 program. I know some of the questions were already answered. But one of your peers just announced the discontinuation of their CDK2 program. I was wondering if you can help us understand how you see the competitive landscape given your data. And before you have the conversation with the FDA or before you move into pivotal trials, should we expect to see any additional data from either ovarian cancer or any of the other indications that you're investigating the drug in? Thank you.

嘿，夥計們。非常感謝您提出我的問題，並祝賀本季恢復正常。我有一個關於 CDK2 程式的問題。我知道有些問題已經得到解答。但您的一位同行剛剛宣布終止他們的 CDK2 計劃。我想知道您是否可以幫助我們了解您如何看待根據您的數據的競爭格局。在您與 FDA 進行對話之前或在進行關鍵試驗之前，我們是否應該期望看到來自卵巢癌或您正在研究該藥物的任何其他適應症的任何其他數據？謝謝。

Let me take that question. So in terms of competitive landscape, the competitive landscape for CDK2 is a little bit beyond the mechanism, right? I mean, we think when it comes to ovarian cancer, we are ahead in terms of developing a CDK2 program. We are -- we disclosed the data, as you know. We have over 200 patients treated. We explore a range of doses. We've seen clear evidence of efficacy and a very, very manageable safety profile.

讓我來回答這個問題。那麼從競爭格局來看，CDK2的競爭格局有點超出了機制，對吧？我的意思是，我們認為在卵巢癌方面，我們在開發 CDK2 專案方面處於領先地位。如您所知，我們揭露了數據。我們已經治療了 200 多名患者。我們探索了一系列劑量。我們已經看到了明顯的功效證據和非常非常易於管理的安全性。

So we intend to start registrational studies next year, which I think that puts us in front when it comes to CDK2 inhibition in ovarian cancer and perhaps also in endometrial cancer. We're doing additional work in other indications.

因此，我們打算明年開始註冊研究，我認為這使我們在卵巢癌甚至子宮內膜癌的 CDK2 抑制方面處於領先地位。我們正在其他適應症方面做額外的工作。

Now the company landscape is a little bit more complicated than just CDK2 because there's a number of ADCs being developed in ovarian cancer. Obviously, rituximab is approved for certain patients with full receptor alpha expression. There are other ADCs, the same target as well as additional targets for ADCs.

現在公司的情況比 CDK2 稍微複雜一些，因為有許多針對卵巢癌的 ADC 正在開發中。顯然，利妥昔單抗被批准用於某些受體 α 完全表達的患者。還有其他 ADC、相同的目標以及 ADC 的其他目標。

I think that the two points I would make is, number one, there isn't complete overlap when it comes to populations, at least now with receptor alpha-positive patients. Perhaps for some of the others, the overlap will be it'll be more pronounced. But one of the reasons why we believe the maintenance study in combination with bevacizumab is very important for us in the long run is because that might be the perfect setting for an oral, convenient, well-tolerated molecules such as our CDK2 inhibitor. So while we intend to move aggressively into platinum-resistant patients to get a faster market strategy there, we believe the maintenance will differentiate our CDK2 program, not only from other entrants in the same target but also against ADCs.

我認為我要指出的兩點是，第一，在人群方面並不完全重疊，至少現在對於受體α陽性患者來說是這樣。也許對於其他一些人來說，重疊會更加明顯。但我們相信從長遠來看，與貝伐單抗聯合維持研究對我們非常重要的原因之一是，這可能是口服、方便、耐受性良好的分子（例如我們的CDK2 抑制劑）的完美環境。因此，雖然我們打算積極進軍鉑類抗藥性患者領域，以便在那裡制定更快的市場策略，但我們相信，維護將使我們的CDK2 項目與眾不同，不僅與同一目標的其他進入者相比，而且與ADC 相比。

Ren Benjamin, JMP Securities.

任本傑明，JMP 證券。

Hey, thanks guys for squeezing me in and congrats on the quarter. I guess just when we think about the potential for positive Phase 3 data from STOP-HS1 and HS2, do you need even like longer-term follow-up data? Or do you feel that you can file kind of right away? And assuming an approval in 2026, how do you see this being used in relation to currently approved therapies? And what kind of market share do you think you might ultimately achieve? I know Steven has talked about greater than 300,000 patients, but how many patients do you think you might be able to treat?

嘿，謝謝大家擠我進來，恭喜這個季度。我想當我們考慮 STOP-HS1 和 HS2 的積極第 3 階段資料的潛力時，您是否需要更長期的後續資料？或者您覺得您可以立即提交文件嗎？假設 2026 年獲得批准，您如何看待與目前批准的療法相關的使用？您認為您最終可能會獲得什麼樣的市場佔有率？我知道史蒂文談到了超過 30 萬名患者，但您認為您可以治療多少患者？

So Ren, it's Steven. I'll at least do the first part to your question. And obviously, we can't speak about a lot of the regulatory aspects. But it is an NDA, a first filing. So there will be safety data that will be needed, and we'll provide updates at the appropriate time, but we continue to guide to a 2026 approval for that at the time.

雷恩，是史蒂文。我至少會回答你問題的第一部分。顯然，我們不能談論很多監管方面的問題。但這是一份保密協議，是首次申請。因此，我們將需要安全數據，我們將在適當的時間提供更新，但我們將繼續指導當時的 2026 年批准。

In terms of -- it will be really up to what you see ultimately in terms of the efficacy profile vis-a-vis other orals or biologics in terms of use. There are a lot of patients with the disease, a lot of unmet need, and there will be a lot of cycling through therapy. I think the numbers we give is between 150,000 to 300,000 patients with this moderate to severe in total, in terms of seeking therapy potentially. And then use of biologics versus orals, et cetera, will depend on the profiles of the drugs from the Phase 3 setting. Thanks.

就使用而言，這實際上取決於您最終看到的與其他口服藥物或生物製劑相比的功效。有許多患有這種疾病的患者，有很多未滿足的需求，並且會有許多循環治療。我認為，就潛在尋求治療而言，我們給出的數字為 150,000 至 300,000 名中度至重度患者。然後使用生物製劑與口服製劑等，將取決於第三階段藥物的概況。謝謝。

Thank you. We reach the end of our question-and-answer session. I'd like to turn the floor back over to Ben for any further closing comments.

謝謝。我們的問答環節即將結束。我想將發言權交還給本，以徵求更多的結論。

Thank you all for participating in the call today and your questions. The IR team will be available for the rest of the day for follow-up. Thank you and goodbye.

感謝大家參加今天的電話會議並提出問題。IR 團隊將在當天剩餘時間進行跟進。謝謝你，再見。

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.

謝謝。今天的電話會議和網路廣播到此結束。此時您可以斷開線路，度過美好的一天。我們感謝您今天的參與。