英賽德 (INCY) 2024 Q4 法說會逐字稿

Greetings and welcome to the Incyte fourth-quarter 2024 and full-year financial and corporate update conference call webcast. (Operator Instructions) As a reminder, this conference is being recorded.

問候並歡迎參加 Incyte 2024 年第四季和全年財務和公司更新電話會議網路直播。（操作員指示）提醒一下，本次會議正在錄音。

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

現在我可以接聽電話了嗎？交給投資人關係副總裁 Ben Strain 吧。請繼續，本。

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

謝謝你，凱文。早上好，歡迎參加 Incyte 2024 年第四季和全年財報電話會議。在我們開始之前，我鼓勵大家造訪我們網站的投資者部分，尋找新聞稿、相關財務表格以及今天討論之後的幻燈片。在今天的電話會議上，Herve、Pablo、Christiana 將與我一起發表準備好的演講； Matteo 和 Steven 也將參與問答環節。

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 actual results may differ materially. I encourage you to consult the risk factors discussed at SEC filings for additional detail. I will now hand the call over to Herve.

我想指出的是，我們將根據我們目前的預期和信念做出前瞻性的陳述。這些聲明受一定風險和不確定性的影響，實際結果可能有重大差異。我鼓勵您查閱美國證券交易委員會 (SEC) 文件中討論的風險因素以獲取更多詳細資訊。我現在將電話交給埃爾維。

Thank you, Ben, and good morning, everyone. So we delivered another strong year with 2024, total revenues growing 15% versus 2023, to reach $4.2 billion, continuing the steady growth we have delivered since 2020.

謝謝你，本，大家早安。因此，我們在 2024 年又度過了強勁的一年，總收入較 2023 年增長 15%，達到 42 億美元，延續了自 2020 年以來的穩步增長。

In addition to the consistent performance of Jakafi in 2024, we saw strong growth from our non-Jakafi revenue, primarily driven by Opzelura, highlighting our continuing revenue diversification.

除了 Jakafi 在 2024 年的穩定表現外，我們還看到非 Jakafi 收入的強勁增長，這主要得益於 Opzelura，凸顯了我們持續的收入多元化。

Moving to slide 6. In 2024, Jakafi net sales were $2.8 billion, growing 8% versus the prior year, with growth coming from all indications. Opzelura saw strong continued momentum in 2024, growing 50% to $508 million, driven by both new patients and refills in AD and Vitiligo in the US, and expanding reimbursement outside the US. We expect Opzelura to continue to be a key contributor to growth in the next year.

移至幻燈片 6。2024年，Jakafi 淨銷售額為 28 億美元，較上年成長 8%，成長來自各方面的跡象。Opzelura 在 2024 年繼續保持強勁勢頭，成長 50%，達到 5.08 億美元，這得益於美國 AD 和白斑的新患者和續藥，以及美國以外地區報銷範圍的擴大。我們預計 Opzelura 將在明年繼續成為成長的主要貢獻者。

Our cash flow remains strong, which allowed us to complete the $2 billion share repurchase during 2024, while maintaining a strong balance sheet. We ended 2024 with $2.2 billion in cash and no debt. We are in a very strong financial position with growing revenues and a robust pipeline that will deliver a number of very exciting readouts in 2025.

我們的現金流依然強勁，這使我們能夠在 2024 年完成 20 億美元的股票回購，同時保持強勁的資產負債表。截至 2024 年，我們擁有 22 億美元現金，且沒有債務。我們的財務狀況非常強勁，收入不斷增長，並且擁有強大的產品線，將在 2025 年提供一系列非常令人興奮的數據。

Last month, we and our partner Syndax announced that the FDA approved Niktimvo in 9 milligram and 22 milligram vial sizes, paving the way for the commercial launch. This medicine is now available in the US, and the commercial launch is underway. Niktimvo is the first anti-CSF-1R antibody approved to target the inflammation and fibrosis associated with chronic GVHD. And we are excited to bring this new therapy to the approximately 6,000 patients who are currently treated after second line therapy in the US.

上個月，我們和合作夥伴 Syndax 宣布 FDA 批准了 9 毫克和 22 毫克兩種規格的 Niktimvo，為其商業化上市鋪平了道路。該藥物目前已在美國上市，並且正在進行商業發布。Niktimvo 是第一個獲準用於治療與慢性 GVHD 相關的發炎和纖維化的抗 CSF-1R 抗體。我們很高興能將這種新療法帶給美國目前接受第二線治療後約 6,000 名患者。

In addition to the launch of Niktimvo, the sNDA for ruxolitinib cream in pediatric atopic dermatitis was filed with the FDA, and we are on track for potential approval in the second half of 2025. With 2 to 3 million pediatric patients in the US suffering from atopic dermatitis, we see significant opportunities for ruxolitinib cream with its compelling efficacy in controlling itch to address an important need for this patient population.

除了推出 Niktimvo 之外，我們還向 FDA 提交了用於治療兒童異位性皮膚炎的蘆可替尼乳膏的 sNDA，預計將在 2025 年下半年獲得批准。美國有 200 萬至 300 萬名兒科患者患有異位性皮膚炎，我們認為蘆可替尼乳膏具有顯著的控制搔癢功效，可以滿足這類患者群體的重要需求，具有巨大的市場潛力。

We submitted pivotal study results to the FDA for both tafasitamab in follicular lymphoma, and retifanlimab in squamous cell anal carcinoma and anticipate approvals for both in the second half of 2025. These product launches are expected to begin contributing to revenue in the near term with the potential to collectively generate $1 billion in incremental revenues by 2029, further diversifying our revenue.

我們向 FDA 提交了 tafasitamab 在治療濾泡性淋巴瘤和 retifanlimab 在治療鱗狀細胞肛門癌方面的關鍵研究結果，預計這兩種藥物都將在 2025 年下半年獲得批准。這些產品的推出預計將在短期內開始為收入做出貢獻，到 2029 年將有可能共同創造 10 億美元的增量收入，從而進一步實現我們的收入多元化。

We anticipate all four products to be available in '25, and we will be leveraging our existing commercial infrastructure established for Jakafi, Opzelura, Monjuvi, and Pemazyre to support the launches of these new products or indications.

我們預計所有四種產品將於25年上市，我們將利用為 Jakafi、Opzelura、Monjuvi 和 Pemazyre 建立的現有商業基礎設施來支援這些新產品或新適應症的推出。

Moving to slide 9. And an update of the fourth-quarter and full-year 2024 commercial performance for Jakafi. In the fourth quarter, Jakafi net product revenue grew 11% year over year to $773 million and grew 8% for the full year to $2.8 billion. Total patients increased 10% in Q4 when compared to the same quarter in 2023.

移至幻燈片 9。以及 Jakafi 第四季和 2024 年全年商業業績的最新情況。第四季度，Jakafi 淨產品營收年增 11% 至 7.73 億美元，全年成長 8% 至 28 億美元。與 2023 年同期相比，第四季度患者總數增加了 10%。

Importantly, growth is being seen across all indications, but with particular strength in PV, with this indication now accounting for 35% of the patients on Jakafi. We expect continued growth of Jakafi in 2025, and expect the full-year net product revenue for 2025 to be in the range of $2.925 billion to $2.975 billion.

重要的是，所有適應症均呈現成長趨勢，但 PV 的增幅尤為顯著，目前該適應症佔 Jakafi 治療患者的 35%。我們預計Jakafi在2025年將繼續成長，並預計2025年全年淨產品收入將在29.25億美元至29.75億美元之間。

Turning to slide 10 and looking at Jakafi total paid demand by indication during 2022, '23, and 2024. As you can see, unit growth remains robust. Myelofibrosis showed growth again this quarter, while the most significant growth was seen in polycythemia vera. We expect PV to become the largest contributor for Jakafi over time, supported by the data from the MAJIC-PV study, which underscores the benefits of early intervention with Jakafi and its impact on Thrombosis-free survival.

翻到第 10 張投影片，查看 2022 年、2023 年和 2024 年 Jakafi 按適應症劃分的總付費需求。如您所見，單位成長依然強勁。骨髓纖維化本季再次呈現成長態勢，其中真性紅血球增多症的成長最為顯著。我們預計，隨著時間的推移，PV 將成為 Jakafi 的最大貢獻者，這得到了 MAJIC-PV 研究數據的支持，該研究強調了早期幹預 Jakafi 的益處及其對無血栓生存期的影響。

Moving to Opzelura on slide 11, Opzelura net revenue in the fourth quarter was $162 million, up 48%, when compared to the same quarter last year, and this was comprised of $138 million in the US, driven by growth in AD and vitiligo new patients and refills, and $24 million ex-US, driven by growth in Germany and France.

轉到幻燈片 11 上的 Opzelura，Opzelura 第四季度的淨收入為 1.62 億美元，與去年同期相比增長 48%，其中美國淨收入為 1.38 億美元，主要得益於 AD 和白癜風新患者和續藥的增長，美國以外收入為 2400 萬美元，主要得益於德國和法國的增長。

Total 2024 full-year net revenue grew 50% versus 2023, to reach $508 million. In the US, the annual prescription trends for 2022, '23, and 2024, as shown on the right of slide 11, reflects continued year-over-year growth of Opzelura from both atopic dermatitis and vitiligo.

2024 年全年淨收入總額較 2023 年成長 50%，達到 5.08 億美元。在美國，2022 年、2023 年和 2024 年的年度處方趨勢（如幻燈片 11 右側所示）反映了 Opzelura 在治療異位性皮膚炎和白斑症方面的持續逐年增長。

We anticipate continued growth of Opzelura in 2025, and expect the full-year net product revenue to be in the range of $630 million to $670 million.

我們預計 Opzelura 在 2025 年將繼續成長，並預計全年淨產品收入將在 6.3 億美元至 6.7 億美元之間。

On slide 12; so 2025 will be a year of defining catalyst that will provide an inflection point for Incyte. As you can see highlighted on slide 12, every program has a meaningful milestones expected in 2025. This includes four potential launches collectively providing important near-term revenue potential, where the launch of Niktimvo is already underway, as I just highlighted.

在第 12 張投影片上；因此，2025 年將成為定義催化劑的一年，為 Incyte 提供一個轉折點。正如您在投影片 12 上所看到的，每個專案都有一個預計在 2025 年實現的重要里程碑。其中包括四個潛在的發布，它們共同提供了重要的近期收入潛力，其中 Niktimvo 的發布已經在進行中，正如我剛才強調的那樣。

Additionally, we plan to initiate at least three Phase 3 studies, including our BET inhibitor, rux cream in mild to moderate HS, and our CDK2 inhibitor in ovarian cancer. We expect 2025 will be a data-rich year with four pivotal data readouts including Ruxolitinib XR, which Pablo will highlight shortly. More importantly, we expect seven early-stage programs to generate informative data which we believe have the potential to transform the company.

此外，我們計劃啟動至少三項 3 期研究，包括我們的 BET 抑制劑、用於治療輕度至中度 HS 的 rux 乳膏以及用於治療卵巢癌的 CDK2 抑制劑。我們預計 2025 年將是數據豐富的一年，將有四個關鍵數據讀數，包括 Ruxolitinib XR，Pablo 將很快重點介紹。更重要的是，我們預計七個早期專案將產生資訊數據，我們相信這些數據有可能改變公司。

Before I hand the call over to Pablo, I would like to provide a leadership update for our commercial organization. After a remarkable decade of dedicated service to Incyte, Barry Flannelly has decided to retire from his role as Executive Vice President and Head of US oncology. We are pleased to announce that Mohamed Issa assumed Barry's role in January. And Mohamed has successfully led US commercial teams in oncology, immunology, and neuroscience, most recently at J&J.

在我將電話交給 Pablo 之前，我想先介紹一下我們商業組織的領導層最新情況。在為 Incyte 奉獻了十年之久後，Barry Flannelly 決定從其執行副總裁兼美國腫瘤學負責人的職位上退休。我們很高興地宣布，穆罕默德·伊薩於一月份接任了巴里的職位。穆罕默德成功領導了美國腫瘤學、免疫學和神經科學領域的商業團隊，最近在強生公司任職。

I will now turn the call over to Pablo.

現在我將電話轉給 Pablo。

Thank you, Herve, good morning. As we highlighted a year ago, and we summarized on this slide, we remain on track to deliver more than 10 high impact launches by 2030 from programs across the portfolio.

謝謝你，埃爾維，早安。正如我們一年前所強調的並在這張投影片中總結的那樣，我們仍有望在 2030 年前從整個投資組合的專案中推出 10 多個具有高影響力的發射專案。

On slide 15, I would like to quickly highlight some of the key accomplishments during 2024, and I will then cover some of the milestones expected in 2025. We had a number of important regulatory achievements in 2024, including the approval of Niktimvo for third line plus chronic graft-versus-host disease, and three submissions to the FDA with expected approvals later this year, including Opzelura in pediatric atopic dermatitis, retifanlimab in SCAC, and tafasitamab in relapsed or refractory follicular lymphoma.

在第 15 張投影片上，我想快速強調 2024 年的一些主要成就，然後我將介紹 2025 年預期的一些里程碑。我們在 2024 年取得了許多重要的監管成就，包括 Niktimvo 獲批用於治療三線以上慢性移植物抗宿主病，以及三份向 FDA 提交的申請，預計將於今年晚些時候獲得批准，包括用於治療兒童特應性皮膚炎的 Opzelura、用於治療小細胞肺癌的 retifanlimab 和用於治療復發或難治性濾泡性淋巴瘤的 ttam

We disclosed data from our CDK2 inhibitor and BET inhibitor programs and provided pivotal study plans for both, which we anticipate initiating this year. We continue to evolve at R&D focus with the intent of increasing the rigor of our decision making, accelerating the progression of our pipeline, and optimizing our resource allocation.

我們公開了 CDK2 抑制劑和 BET 抑制劑項目的數據，並為這兩個項目提供了關鍵研究計劃，預計今年將啟動。我們將持續加強研發重點，以提高決策的嚴謹性、加速產品線的進展和優化資源配置。

Through the fourth quarter of 2024, we presented data at the American Society of Hematology annual meeting or ASH, from both our BET inhibitor program and Phase 3 results for tafasitamab in patients with relapsed or refractory follicular lymphoma. The Phase 3 results of tafasitamab in follicular lymphoma were presented at a late breaking session and showed that the study met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression free survival.

到 2024 年第四季度，我們在美國血液學會年會或 ASH 上展示了我們的 BET 抑制劑計劃和他法西單抗治療復發或難治性濾泡性淋巴瘤患者的 3 期結果的數據。他法西單抗治療濾泡性淋巴瘤的 3 期研究結果在最新進展會議上公佈，結果顯示該研究達到了其主要終點，在無進展生存期方面表現出統計學和臨床意義上的顯著改善。

This was to our knowledge, the first study to validate the combination of an anti-CD19 with an anti-CD20 monoclonal antibodies in patients with follicular lymphoma. tafasitamab was generally well tolerated, and safety was consistent with its known safety profile.

據我們所知，這是第一個驗證抗 CD19 與抗 CD20 單株抗體在濾泡性淋巴瘤患者中的合併使用的研究。他法西單抗通常耐受性良好，且安全性與其已知的安全性一致。

This data has been submitted to the FDA, and approval is expected in the second half of 2025. For our BET inhibitor, we shared additional data from the ongoing dose escalation study as both monotherapy and in combination with ruxolitinib. These results showed reductions in spleen volume as well as improvements in both symptoms and hemoglobin.

該數據已提交給FDA，預計將於2025年下半年獲得批准。對於我們的 BET 抑制劑，我們分享了正在進行的劑量遞增研究的額外數據，包括單一療法和與蘆可替尼聯合使用。這些結果顯示脾臟體積減少以及症狀和血紅素均有所改善。

As highlighted on this slide, we plan to advance this program into Phase 3 development as a monotherapy in the post-JAK population, and we look forward to providing additional details later this year.

正如本幻燈片所強調的，我們計劃將該項目推進到第 3 階段開發，作為 JAK 後人群的單一療法，我們期待在今年晚些時候提供更多細節。

Moving to slide 18, we are 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 chronic spontaneous urticaria and asthma, with data for both expected in 2025.

轉到第 18 張投影片，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。目前，povorcitinib 正在針對化膿性汗腺炎、白斑症和結節性癢疹進行 3 期研究，以及針對慢性自發性蕁麻疹和氣喘進行隨機 2 期概念驗證研究，預計兩項研究的數據將於 2025 年公佈。

Povorcitinib has already shown encouraging efficacy and safety in a randomized Phase 2 study in patients with moderate to severe Hidradenitis Suppurativa, a highly painful inflammatory condition. As highlighted on the right side of the slide 19, but povorcitinib showed significant responses by week 12, including improvements in high score 50, 90, and 100. Additionally, povorcitinib demonstrated a rapid and significant reduction in pain, offering the potential to transform the current standard of care for this disease.

在一項針對中度至重度化膿性汗腺炎（一種非常疼痛的發炎疾病）患者的隨機 2 期研究中，povorcitinib 已經顯示出令人鼓舞的療效和安全性。正如幻燈片 19 右側所強調的那樣，但 povorcitinib 在第 12 週顯示出顯著的反應，包括高分 50、90 和 100 的改善。此外，povorcitinib 也表現出快速且顯著減輕疼痛的作用，有可能改變這種疾病的現行治療標準。

The two Phase 3 studies, STOP-HS1 and STOP-HS2, are fully enrolled, and we expect to have Phase 3 data in the first half of this year.

兩個 3 期研究 STOP-HS1 和 STOP-HS2 都已完全招募參與者，我們預計今年上半年將獲得 3 期數據。

Turn to the mutant CALR antibody program on slide 20. The publication detailing our mutant CALR monoclonal antibody was recently featured on the cover of Blood, highlighting the importance of this innovative medicine. This antibody was developed entirely by Incyte, and unlike Jakafi, the mutant CALR antibody has the potential to eliminate the mutant clone and normalize hematopoiesis in patients with CALR mutated essential thrombocythemia and myelofibrosis, potentially leading to a functional cure. We look forward to sharing data from the ongoing proof of concept studies in both ET and MF later this year.

前往幻燈片 20 上的突變 CALR 抗體程式。詳細介紹我們的突變型 CALR 單株抗體的出版物最近登上了《血液》雜誌的封面，凸顯了這種創新藥物的重要性。該抗體完全由 Incyte 開發，與 Jakafi 不同的是，突變型 CALR 抗體有可能消除突變克隆，並使 CALR 突變型原發性血小板增多症和骨髓纖維化患者的造血正常化，從而有望實現功能性治癒。我們期待今年稍後分享 ET 和 MF 正在進行的概念驗證研究的數據。

Turn to slide 21 on Ruxolitinib XR. We're pleased to announce that a bio-equivalency study of ruxolitinib 55 milligrams extended release demonstrated that once-a-day formulation to be bio-equivalent to twice-a-day ruxolitinib. Bio-equivalence was achieved for both AUC and C-min, and the geometric means ratios falling within the 80% to 125% bio-equivalence reference range. We have reviewed this data with the FDA, and with their agreement, plan to submit for approval by the end of the year once stability studies are completed.

前往有關 Ruxolitinib XR 的第 21 張投影片。我們很高興地宣布，蘆可替尼 55 毫克緩釋片的生物等效性研究表明，每日一次的配方與每日兩次的蘆可替尼具有生物等效性。AUC 和 C-min 均達到了生物等效性，且幾何平均比率在 80% 至 125% 的生物等效性參考範圍內。我們已經與 FDA 一起審查了這些數據，並在他們的同意後，計劃在穩定性研究完成後於年底前提交批准。

As mentioned, 2025 will be an important year for Incyte, with over 18 key milestones, including 4 new product launches, 4 pivotal trial readouts, at least 3 Phase 3 study initiations, and 7 proof of concept study results. As you can see on slide 22, we have already achieved 2 of these milestones that we first highlighted just last month with the launch of Niktimvo and bio-equivalency data for ruxolitinib extended release.

如上所述，2025 年對 Incyte 來說將是重要的一年，將有超過 18 個關鍵里程碑，包括 4 個新產品發布、4 個關鍵試驗讀數、至少 3 個 3 期研究啟動和 7 項概念驗證研究結果。正如您在第 22 張幻燈片上看到的，我們已經實現了其中兩個里程碑，我們上個月首次強調這兩個里程碑，即 Niktimvo 的推出和蘆可替尼緩釋片的生物等效性數據。

We look forward to sharing additional updates on these milestones over the course of 2025, and with that, I would like to turn the call over to Christiana for the financial update.

我們期待在 2025 年期間分享這些里程碑的更多更新內容，同時，我想將電話轉給克里斯蒂安娜 (Christiana) 以提供財務更新。

Thank you Pablo, and good morning everyone. Our fourth-quarter 2024 results reflect a strong commercial execution and continued growth with total revenues of $1.2 billion, up 16% versus the same period last year. Total product revenues of $1 billion in Q4 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 in 2024. Total royalty revenues were $159 million, up 6% compared to Q4 2023, driven by increased demand for Jakafi.

謝謝 Pablo，大家早安。我們的 2024 年第四季業績反映了強勁的商業執行和持續的成長，總營收為 12 億美元，比去年同期成長 16%。第四季總產品收入達到 10 億美元，主要得益於 Jakafi 和 Opzelura 的強勁需求增長，以及 2024 年收購 tafasitamab 全部權利後 Monjuvi 的收入貢獻增加。受 Jakafi 需求增加的推動，特許權使用費總收入為 1.59 億美元，比 2023 年第四季成長 6%。

Turning to Jakafi on slide 26. Jakafi net products revenue was driven by strong patient demand growth across all indications. In the fourth quarter of 2024, net product revenue increased 11% year over year, driven by a 9% increase in total demand and a 14% increase in paid demand. For the full-year 2024, net product revenue increased 8% versus 2023, driven by a 7% increase in total demand and a 9% increase in paid demand.

轉到第 26 張投影片上的 Jakafi。Jakafi 淨產品收入主要得益於各適應症患者需求強勁成長。2024年第四季，淨產品營收年增11%，這得益於總需求成長9%和付費需求成長14%。2024 年全年，淨產品收入較 2023 年增長 8%，這得益於總需求增長 7% 和付費需求增長 9%。

Recall that in Q3 and Q4 2023, we saw a significant increase in the number of Medicare Part D patients receiving free product. As we anticipated, these patients returned to paid demand in 2024. As a result, year year-over-year paid demand growth exceeded total demand growth in both the fourth-quarter and full-year 2024.

回想一下，在 2023 年第三季和第四季度，我們看到獲得免費產品的 Medicare Part D 患者數量顯著增加。正如我們預期的那樣，這些患者的付費需求將在 2024 年恢復。因此，2024 年第四季和全年的付費需求年增率都超過了總需求成長。

Turning now to Opzelura on slide 27. Total net product revenue for the fourth quarter was $162 million, representing a 48% increase year over year, 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.

現在轉到第 27 張幻燈片上的 Opzelura。第四季總淨產品收入為 1.62 億美元，年增 48%，這得益於美國阿茲海默症和白斑新患者開始治療和續藥數量的增長，以及 Opzelura 在歐洲白斑藥物商業化的持續貢獻。

In the fourth quarter, ex-US Opzelura net product revenue was $24 million. For the full year, net product revenue was $508 million, representing a 50% increase year over year, and ex-US net product revenue was $61 million.

第四季度，美國以外Opzelura淨產品收入為2,400萬美元。全年淨產品收入為 5.08 億美元，年增 50%，其中美國以外淨產品收入為 6,100 萬美元。

Moving on to slide 28 and our operating expenses, total GAAP R&D expenses for the fourth quarter were $466 million, an increase of 5% compared to the same period in '23, due to continued investment in our late-stage development assets and timing of certain expenses.

繼續查看第 28 張投影片和我們的營運費用，第四季的 GAAP 研發費用總額為 4.66 億美元，與 23 年同期相比成長 5％，這歸因於我們對後期開發資產的持續投資以及某些費用的時機。

For the full-year 2024, ongoing R&D expenses, excluding the Escient acquisition upfront consideration and other one-time expenses, increased 14% year over year as a result of increased investment in our late-stage programs.

2024 年全年，由於對後期專案的投資增加，持續研發費用（不包括 Escient 收購前期對價和其他一次性費用）年增 14%。

As we wrap up the clinical developments of certain of these programs 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.

隨著我們完成某些項目的臨床開發以及已停止項目的開發活動，我們預計對這些項目的投資減少將部分抵消對其他項目的投資增加，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 $327 million for the fourth quarter, representing an 11% year-over-year increase, primarily as a result of Incyte's now recording Monjuvi-related sales and marketing expenses in the US, following the acquisition of global rights to the program in 2024, as well as the timing of consumer marketing activities and certain other expenses.

轉向銷售、一般及行政開支；第四季度，GAAP 銷售、一般及行政管理費用總額為 3.27 億美元，年增 11%，這主要是由於 Incyte 在 2024 年收購該計劃的全球權利後，現在在美國記錄了與 Monjuvi 相關的銷售和營銷費用，以及消費者營銷活動的時機和某些其他費用。

For the full-year 2024, total GAAP SG&A expenses increased 7% year over year, as a result of us now recording Monjuvi-related sales and marketing expenses, and investment in the launch of Opzelura in Europe and the preparation for new product launches in the US.

2024 年全年，GAAP 銷售、一般及行政管理總​​費用年增 7%，原因是我們現在記錄了與 Monjuvi 相關的銷售和行銷費用，以及對在歐洲推出 Opzelura 以及在美國推出新產品的準備的投資。

Finally, total ongoing R&D and SG&A expense for the full year increased 10% versus a 15% increase in total revenues, leading to an increase in operating leverage and margins.

最後，全年持續研發和銷售、一般及行政開支總額增長了 10%，而總收入增長了 15%，從而導致經營槓桿和利潤率上升。

Moving on to 2025, I will now discuss the key components of our guidance on a GAAP basis. For Jakafi, we expect net products revenue to be in the range of $2.925 billion to $2.975 billion, well on track to achieve our long-term guidance of over $3 billion by 2028.

展望 2025 年，我現在將根據 GAAP 討論我們指引的關鍵要素。對於 Jakafi，我們預計淨產品收入將在 29.25 億美元至 29.75 億美元之間，預計將實現我們到 2028 年超過 30 億美元的長期預期。

We expect net product revenue growth to be driven exclusively by continued demand growth, primarily in PB, and be partially offset by lower net pricing as a result of IRA-imposed price increase caps and continued growth in 340B volumes.

我們預計淨產品收入成長將完全由持續的需求成長（主要是 PB）推動，而由於 IRA 施加的價格上漲上限和 340B 銷量的持續成長導致的淨定價下降將部分抵消淨收入成長。

As in previous years, we expect the gross to net adjustment to be higher in the first quarter of the year, relative to the previous quarter and subsequent quarters, due to higher deductibles that are primarily impacting Q1.

與往年一樣，我們預計今年第一季的總淨調整額將高於上一季和後續季度，這是由於較高的免賠額主要影響第一季。

For Opzelura, we expect total net product revenue to be in the range of $630 million to $670 million, driven by continued demand growth in AD and vitiligo in the US, initial contribution from the potential launch of Opzelura for pediatric AD, expected in the second half of the year, and increased contribution from Opzelura for vitiligo in Europe.

對於 Opzelura，我們預計總淨產品收入將在 6.3 億美元至 6.7 億美元之間，這得益於美國對 AD 和白斑的需求持續增長，預計下半年將推出用於治療兒科 AD 的 Opzelura 的初步貢獻，以及 Opzelura 在歐洲用於治療白癜風的貢獻增加。

In the first quarter of the year, we expect to see again the effects of typical Q1 dynamics on nets sales, due to planned deductibles resetting at the beginning of the year and the impact of holidays, medical conferences, and other events on dermatology product sales. As a result, Q1 Opzelura net product revenue is expected to be below the previous quarter, consistent with what we saw in 2024.

今年第一季度，我們預計將再次看到典型的第一季度動態對淨銷售額的影響，這是由於年初計劃免賠額重置以及假期、醫學會議和其他活動對皮膚病學產品銷售的影響。因此，預計 Opzelura 第一季淨產品收入將低於上一季度，與我們在 2024 年看到的情況一致。

For other oncology products, we expect total net product revenues to be in the range of $415 million to $455 million. These include contribution from both the current approved indications for our exclusive Niktimvo Monjuvi/Minjuvi, Pemazyre and Zynyz, as well as the launches of Monjuvi in SL and Zynyz in SCAC, anticipated in the second half of 2025.

對於其他腫瘤產品，我們預計總淨產品收入將在 4.15 億美元至 4.55 億美元之間。這些貢獻包括我們目前批准的獨家 Niktimvo Monjuvi/Minjuvi、Pemazyre 和 Zynyz 適應症，以及預計在 2025 年下半年在 SL 推出的 Monjuvi 和在 SCAC 推出的 Zynyz。

Turning to operating expenses on a GAAP basis, we expect COGS to range from 8.5% to 9% of net product revenues. The increase in the COGS rate is driven by certain manufacturing related expenses and the impact of our profit share agreement with Syndax for Niktimvo in the US, as Syndax's portion of the profit share will be reflected in COGS.

根據 GAAP 計算的營業費用，我們預計 COGS 將佔淨產品收入的 8.5% 至 9%。銷貨成本率的上升是由某些製造相關費用以及我們與 Syndax 就美國 Niktimvo 達成的利潤分享協議的影響所推動的，因為 Syndax 的利潤分享部分將反映在銷貨成本中。

R&D expenses are expected to be in the range of $1.93 billion to $1.96 billion, primarily driven by the progression of our pipeline. We expect SG&A expenses for the year to be in the range of $1.28 billion to $1.31 billion.

研發費用預計在 19.3 億美元至 19.6 億美元之間，主要受我們產品線進展的推動。我們預計全年銷售、一般及行政開支將在 12.8 億美元至 13.1 億美元之間。

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

接線員，我們的準備發言到此結束。請給予您的指示並開啟問答環節。

(Operator Instructions)

（操作員指令）

Michael Schmidt, Guggenheim Partners.

古根漢合夥人公司的麥可‧施密特。

Hey, good morning. Thanks for taking our question. This is Paul on for Michael. We have two on the pipeline. First on Opzelura. Can you set some expectations for the upcoming Phase 3 in prurigo nodularis? What's the clinical bar here given there's no topical therapies available? And then secondly, just on the CDK2 program. Are there any plans to provide another clinical update on the Phase 1 ovarian cancer study, perhaps with longer follow-up at the expansion dose levels? And what are the gating factors to formalizing a pivotal study dose selection?

嘿，早安。感謝您回答我們的問題。這是保羅，代替麥可。我們有兩個正在籌備中。首先是 Opzelura。您能對結節性癢疹即將到來的第 3 階段做出一些期望嗎？鑑於沒有可用的局部治療方法，這裡的臨床標準是什麼？其次，僅討論 CDK2 程序。是否有計劃對第一階段卵巢癌研究提供另一項臨床更新，或許在擴展劑量水平進行更長時間的追蹤？那麼，正式確定關鍵研究劑量選擇的決定因素是什麼？

Thank you.

謝謝。

Certainly. Thank you for the questions. Let me take the second one real quick. For the CDK2 program, as we discussed earlier, this year, we plan to initiate pivotal trials this year. And as we discussed, that will be in platinum-resistant ovarian cancer. We've taken a dual approach there with a single-arm study for what we hope will be accelerated approval in the US as well as a randomized trial that we will provide more details over the course of the year. So that program is advancing rapidly, and we will provide an update later this year as you asked.

當然。感謝您的提問。讓我快速回答第二個問題。對於 CDK2 計劃，正如我們之前討論過的，我們計劃今年啟動關鍵試驗。正如我們所討論的，這將適用於鉑金抗藥性卵巢癌。我們採取了雙重方法，首先是單臂研究，我們希望研究能夠在美國加速獲得批准，其次是隨機試驗，我們將在今年提供更多細節。該計劃正在迅速推進，我們將按照您的要求在今年稍後提供最新消息。

The second part of the question in terms of terms of Rux cream in prurigo nodularis. As you know, the Phase 3 data are coming in this half. And I think what -- in terms of setting the bar, when you look at the Phase 2 data and the improvement, both on the global assessment of itching as well as the WNRS end point, we think that if we are anywhere in the vicinity of what the Phase 2 trial showed, this is going to be a very important addition to the armamentarium for patients with prurigo nodularis.

問題的第二部分是關於 Rux 乳膏在治療結節性癢疹方面的。如您所知，第三階段的數據將在本半年內公佈。我認為 — — 在設定標準方面，當您查看第 2 階段的數據和改善情況時，無論是從瘙癢的整體評估還是 WNRS 終點來看，我們認為如果我們的療效接近第 2 階段試驗的結果，那麼這將是結節性癢疹患者的治療手段的一個非常重要的補充。

The availability of a topical for patients that have perhaps less severe disease than those that may require systemic medicines such as povorcitinib, we think it's going to be very important. So we want to be somewhere -- and as we all know, from the extensive safety track record of Rux cream it's a very, very well-tolerated medicine. So if we're anywhere near what the Phase 2 results showed, I think we're going to be -- it's going to be a very important contribution for patients.

對於病情可能比需要全身用藥（例如 povorcitinib）的患者輕的患者，我們認為局部用藥非常重要。因此，我們想要達到某種程度——眾所周知，從 Rux 乳膏的廣泛安全記錄來看，它是一種耐受性非常非常好的藥物。因此，如果我們接近第二階段的結果，我認為這將為患者帶來非常重要的貢獻。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi guys, good morning. Thanks for taking my questions. As it relates to Opzelura, can you give us a sense of how you got to guidance for this calendar year, specifically, how are you thinking about the number of tubes that are going to be used for the two approved indications? And then maybe one question on povo or for the HS data that's due in the first half of this year, what would you consider to be not only statistically significant but also clinically meaningful data? Thanks.

大家好，早安。感謝您回答我的問題。至於 Opzelura，您能否向我們介紹一下您如何獲得今年的指導，具體來說，您如何考慮用於兩種核准適應症的管子數量？然後也許有一個關於 povo 或今年上半年即將公佈的 HS 數據的問題，您認為什麼數據不僅具有統計意義而且具有臨床意義？謝謝。

This is Christiana. Regarding the Opzelura guidance. First of all, when you look at the guidance range that we provided to the $630 million to $670 million for the year, it represents 24% to 32% year-over-year growth.

這是克里斯蒂安娜。關於 Opzelura 指導。首先，當您查看我們為今年提供的 6.3 億美元至 6.7 億美元的指導範圍時，這代表著同比增長 24％至 32％。

As we indicated in our prepared remarks, this is driven by continued demand growth in AD and vitiligo and also reflects the potential launch of Opzelura in pediatric AD in the second half, the contribution from that indication and continued increased contribution from Europe.

正如我們在準備好的評論中所指出的，這是由 AD 和白斑的持續需求增長所推動的，也反映了下半年 Opzelura 在兒科 AD 中的潛在推出、該適應症的貢獻以及來自歐洲的持續增長的貢獻。

The range that we provided primarily reflects variations in the patient mix as well as in the level of patient activation rate and adherence in vitiligo and the level of contribution from Europe.

我們提供的範圍主要反映了患者結構的變化以及白斑症患者激活率和​​依從性的水平以及來自歐洲的貢獻水平。

In terms of the tube, the level of tubes, that especially around the vitiligo is reflected in the level of patient activation rate and adherence. We are seeing an increase in the average number of patients that are sticking with therapy, and therefore, refill their prescription, and also in the average number of prescriptions per patient.

就管子而言，特別是在白斑周圍的管子的水平反映在病人激活率和依從性的水平。我們發現堅持接受治療的患者平均數量增加，因此需要重新開藥，而且每位患者的平均處方數量也在增加。

But as we have commented in the past, this is an area that is evolving, and we expect to continue to evolve as we pursue additional initiatives to help patients, educate patients and help them appropriately use vitiligo -- Opzelura for vitiligo. And that is reflected in the guidance range that we have provided.

但正如我們過去所評論的那樣，這是一個正在發展的領域，我們希望繼續發展，因為我們會採取更多舉措來幫助患者、教育患者並幫助他們適當地使用白斑藥物——用於治療白斑的 Opzelura。這反映在我們所提供的指導範圍內。

Finally, the other thing, again, to keep in mind, as you think about the guidance and how do you distribute it through the course of the year. Q1, as I mentioned in my prepared remarks, always tends to be lower than the previous quarter and the subsequent quarters. We saw that in '23, we saw it in '24 when we expect to see the same dynamics in '25.

最後，當您考慮指導以及如何在全年中分配它時，請再次記住另一件事。正如我在準備好的發言中提到的那樣，第一季的業績總是低於上一季和後續季度。我們在23年看到了這一點，我們在24年也看到了這一點，我們預計在25年還會看到同樣的動態。

Let me take the second part of the question. So look, the first and most important thing is obviously to have a positive study or two positive studies, and that, as you know, means statistical significance for the primary endpoint, which, in this case, is HiSCR 50 at week 12 in the two hidradenitis suppurativa studies for povo.

讓我來回答問題的第二部分。因此，首先也是最重要的事情顯然是進行一項或兩項積極的研究，而且如您所知，這意味著主要終點具有統計學意義，在本例中，主要終點是兩項針對 povo 的化膿性汗腺炎研究中第 12 週的 HiSCR 50。

Now beyond that, I think that when one looks at the Phase 2 results with the povorcitinib study and you look at the totality of the data, and that is effect on HiSCR50, 75, 90 and 100 as well has a strong effect on pain improvement that the study showed. Together with the safety profile, the Phase 2 was very clean in that study. There were no thrombotic events in the high-dose povo arm.

除此之外，我認為，當人們查看 povorcitinib 研究的第 2 階段結果並查看全部數據時，就會發現該研究顯示，其對 HiSCR50、75、90 和 100 的影響也對疼痛改善具有很強的影響。結合安全性概況，研究中的第 2 階段非常清晰。高劑量 povo 組沒有發生血栓事件。

There were no patients that discontinued due to adverse events in well that we've seen in Phase 2. And we realize there's always a little bit of contraction in Phase 3,a little bit of -- the results can change a little bit. But we believe the overall profile that we saw in Phase 2, if we are somewhere in the vicinity of replicating those results in the Phase 3 studies, we think we have a very competitive profile with povorcitinib in hidradenitis suppurativa.

在第 2 階段，我們沒有看到任何患者因為不良事件而停藥。我們意識到在第三階段總會有一點點收縮，一點點──結果可能會有一點點變化。但是我們相信，根據我們在第 2 階段看到的整體情況，如果我們在第 3 階段的研究中能夠複製這些結果，那麼我們認為在化膿性汗腺炎方面，povorcitinib 具有非常有競爭力的優勢。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

Thank you very much for taking my question. Given the IRA out-of-pocket has moved to its go-forward levels, 1,000 per year, can you run us through what the processes that a patient must go through to actually ensure that the cap is put in place. What steps do they need to take? And how long do you think it might be until the benefit of that starts showing up in sales?

非常感謝您回答我的問題。鑑於 IRA 自付費用已升至每年 1,000 美元的上限，您能否向我們介紹患者必須經過哪些流程才能真正確保達到上限？他們需要採取什麼措施？您認為多久之後這種做法的好處才會在銷售中反映出來？

So the cap for the out-of-pocket this year is reduced to 2,000 a year. Patients do have an option to have this spread through the course of the year in equal payments. There is a process that they would have to go through. We expect that it would take some time for them to figure out that process. So we may not see the immediate benefit right away, although we expect to see a continued benefit from the lower out-of-pocket as we saw in 2024.

所以今年自付額的上限減少到每年2000元。患者確實可以選擇在全年以均等付款的方式分期付款。他們必須經歷一個過程。我們預計他們需要一些時間來弄清楚這個過程。因此，我們可能不會立即看到直接的好處，儘管我們預計較低的自付費用將繼續帶來好處，就像我們在 2024 年看到的那樣。

Thanks for taking the question.

感謝您回答這個問題。

Jessica Fye, JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

Hey guys, good morning. Thanks for taking my questions. A couple on povo in HS. So I think north of 60% of the patients in your Phase 3 trials are biologic-naive. Are you going to seek a label that includes biologic-naive patients? Or do you expect it will be labeled for post biologic patients? And then within the trials, are you powered for both the biologic naive and experienced subgroups? And is there anything you can say about the powering assumptions there?

嘿，大家早安。感謝您回答我的問題。高中時一對 povo 夫婦。因此，我認為，在你們的 3 期試驗中，超過 60% 的患者都是未使用過生物藥物的患者。您是否要尋找一個包括未接受過生物製劑治療的患者的標籤？或者您預計它將被標記為適用於生物製劑後患者？然後在試驗中，你是否為生物學初級亞組和經驗豐富的亞組都提供了支持？您能談談那裡的驅動假設嗎？

Yeah, Jess. So as you point out, we haven't disclosed a specific percentage, but it's roughly -- directionally, that's correct in terms of biologics naive biologically exposed patients. Our products supports the biologics as a stratification criteria in the Phase 3 trials. We expect to analyze the data based on prior exposure to biologics. I'm not going to comment on the full powering. Obviously, the studies are powered on the basis of assumptions around the primary endpoint and the key secondary endpoints for the study. So we'll discuss the results in more detail. And obviously, in terms of labeling discussions, we'll see what the data looks like, and we'll discuss with FDA at the right time.

是的，傑西。正如您所指出的，我們尚未透露具體的百分比，但從方向上看，對於未接受過生物製劑治療的生物暴露患者而言，這是正確的。我們的產品支持生物製劑作為第 3 階段試驗的分層標準。我們希望根據先前接觸的生物製劑來分析數據。我不會對全力以赴發表評論。顯然，這些研究是基於對研究的主要終點和關鍵次要終點的假設而建立的。因此我們將更詳細地討論結果。顯然，在標籤討論方面，我們會關注數據，並在適當的時候與 FDA 進行討論。

Pablo, can I follow up on one of the responses to, I think it was Tazeen's question. When you said, if you show something that's close to what you showed in Phase 2, that would be super competitive. Because I think the Phase 2 deltas on HiSCR50 differed a little bit, if you look at the 16-week versus the 12-week time point. And I think in Phase 3, it's a 12-week. So when you say close to Phase 2, do you mean close to the 12-week cut of Phase 2 or close to the 16-week?

帕勃羅，我可以跟進一下其中一個答案嗎？正如您所說，如果您展示的東西接近第二階段所展示的東西，那將會非常有競爭力。因為我認為，如果比較 16 週與 12 週的時間點，HiSCR50 的第 2 階段增量會略有不同。我認為第三階段將持續 12 週。所以當您說接近第 2 階段時，您的意思是接近第 2 階段的 12 週還是接近第 16 週？

Yeah, you're correct. So if you remember, the placebo subtracted HiSCR50 at week 12 is 28% and at week 16, it's 17% in the Phase 2 studies. That's, I think, what you're referring to.

是的，你說得對。所以如果你還記得的話，在第 2 階段研究中，第 12 週安慰劑減去 HiSCR50 為 28%，而第 16 週為 17%。我想這就是你所指的。

Look, we selected week 12. It's a key, one of the key difference, I think, when you look at the public data, and not just in HS, but also in PN, for example, is how quickly it works. And that is very important for patients with painful or intensely pruriginous diseases like HS and PN. So that's the importance of the week 12.

看，我們選擇了第 12 週。我認為，當你查看公共資料時，這是一個關鍵的區別，不僅是在 HS，而且在 PN 中，就是它的工作速度有多快。這對於患有 HS 和 PN 等疼痛或嚴重搔癢疾病的患者來說非常重要。這就是第 12 週的重要性。

My comment was referring roughly to replicate the profile that we saw in Phase 2. I don't want to set a number. We're running the Phase 3 studies to have clarity on what the actual benefit of povorcitinib is in large Phase 3 studies, Jess. So any -- the number, the specific percentage that we see is not something we're going to comment on right now, but a profile that is consistent with the Phase 2 is what we expect to see in the Phase 3.

我的評論大致上是指複製我們在第二階段看到的概況。我不想設定一個數字。傑西，我們正在進行第 3 階段研究，以明確 povorcitinib 在大型第 3 階段研究中的實際益處。因此，我們現在不會對任何數字、具體百分比發表評論，但我們希望在第 3 階段看到與第 2 階段一致的概況。

Salveen Richter, Goldman Sachs.

高盛的薩爾文·里希特（Salveen Richter）。

Good morning. Thanks for taking my question. Just a follow-up here on povo. With regard to the Phase 2 data, and we saw this drop from week 12 to week 16. Could you just speak about the read-through to this trial and the risk that may play out there? And then also in your 2025 guidance, just speak to us about how you model for Part D redesign for Jakafi? Thank you.

早安.感謝您回答我的問題。這只是對 povo 的後續報導。就第 2 階段的數據而言，我們看到這一數字從第 12 週下降到第 16 週。能否談談這次試驗的解讀以及可能的風險？然後，在您的 2025 年指導中，請與我們談談您如何為 Jakafi 建立 D 部分重新設計模型？謝謝。

Certainly, I think, look, clinical trials, particularly in diseases like HS, where they have a placebo effect, as you know, you're going to see some movement on the efficacy endpoints, in the efficacy curve over time.

當然，我認為，臨床試驗，特別是對於 HS 等疾病，它們具有安慰劑效應，如你所知，你會看到療效終點、療效曲線隨著時間的推移而發生一些變化。

What we saw in the Phase 2, as both you and the previous caller, Jess, pointed out, was that from week 12 to week 16, there was a drop in the placebo-subtracted response within povo, in the povo arms. It's probably variability and noise related to clinical trials. We are not concerned about that. The studies are well powered to demonstrate what we believe is a statistically significant difference between povo and placebo. And we think we'll see not only statistically significant, but clinically meaningful impact of povo and the primary endpoint, which is HiSCR50 at week 12 as well as the key secondary endpoints, which include obviously other levels of clinical benefit and other time points in the study.

正如您和先前的來電者 Jess 所指出的，我們在第 2 階段看到的是，從第 12 週到第 16 週，povo 組中安慰劑減量反應有所下降。這可能是與臨床試驗相關的變異性和噪音。我們並不擔心這個。這些研究足以證明我們認為的 povo 和安慰劑之間存在統計上的顯著差異。我們認為，我們不僅會看到 povo 具有統計學意義，還會看到其具有臨床意義的影響，其主要終點是第 12 週的 HiSCR50，以及關鍵的次要終點，其中顯然包括研究中的其他臨床益處水平和其他時間點。

Regarding your second question, Salveen, on the impact of the Medicare Part D redesign on gross to net for Jakafi. We do expect to see some savings in Medicare Part D since our contribution to the donut hole will now be replaced by a 1% participation to the catastrophic coverage, given that we have the small biotech exception. However, these savings would be offset by continued increase that we see in 340B.

關於您的第二個問題，Salveen，關於 Medicare Part D 重新設計對 Jakafi 的毛收入與淨收入的影響。我們確實預計會看到聯邦醫療保險 D 部分會有一些節省，因為考慮到我們有小型生物技術例外，我們對甜甜圈洞的貢獻現在將被 1% 的災難性保險參與度所取代。然而，這些節省將被 340B 的持續成長所抵消。

James Shin, Deutsche Bank.

德意志銀行的詹姆斯辛 (James Shin)。

Hey, good morning, guys. I just wanted to follow up on povo STOP-HS1 and 2 Phase 3 trials. How will you disclose this data? Will we get a press release with HiSCR top line followed by full data at the medical conference? And then any update on the X2 program for CSU? Thank you.

嘿，大家早安。我只是想跟進 povo STOP-HS1 和 2 第 3 階段試驗。你們將如何揭露這些數據？我們會在醫學會議上收到包含 HiSCR 頂線資訊的新聞稿以及完整數據嗎？那麼 CSU 的 X2 計劃有任何更新嗎？謝謝。

So on povo for HS, our plan is once we have the data is to disclose in a press release. And almost certainly, we have a call to discuss our results with the investment community. On 262, I don't have an update at this point. We are still completing the valuation of the events that we described late last year in the preclinical financing, the toxicology, and we'll provide an update later this year.

因此，對於 HS，我們的計劃是，一旦我們獲得數據，就在新聞中披露。幾乎可以肯定的是，我們會與投資界討論我們的績效。在 262 上，我目前沒有更新。我們仍在完成去年年底在臨床前融資、毒理學中描述的事件的評估，並將在今年稍後提供最新消息。

Vikram Purohit, Morgan Stanley.

摩根士丹利的維克拉姆·普羅希特（Vikram Purohit）。

Hi, good morning. Thanks for taking our questions. We had just one on the proof-of-concept data sets expected for [you and keller] then also for JAK2V617Fi for later this year. Could you just help us kind of frame what we can expect to learn and what you're setting at the bar for success for these data sets and what the hurdle is going to be for moving these programs forward?. Thank you.

嗨，早安。感謝您回答我們的問題。我們只有一個針對 [你和凱勒] 的概念驗證資料集，並且還將在今年稍後針對 JAK2V617Fi 進行驗證。您能否幫助我們概括一下我們可以期望學到什麼、您為這些資料集設定的成功標準是什麼以及推動這些程式向前發展的障礙是什麼？謝謝。

So let me start with mutant-CALR. So as you point out, we'll have proof-of-concept data this year for both patients with ET and MF. That will come over the course of the year. What we expect to see and just to -- first of all, let me tell you a little bit about what you're going to see, and it's going to be a substantive amount of data. We expect to have data at different dose levels with some amount of follow-up in order to have clarity on some of the important measures of success for those programs.

因此讓我從突變 CALR 開始。正如您所指出的，今年我們將為 ET 和 MF 患者提供概念驗證數據。這將在今年內實現。我們期望看到什麼——首先，讓我告訴您一些您將要看到的內容，這將是大量的數據。我們希望獲得不同劑量水平的數據並進行一定程度的跟踪，以便明確這些項目成功的一些重要指標。

Obviously, we discussed over the past few months the importance for this program, not only to show an impact on the traditional endpoints in patients with myeloproliferative neoplasms such as blood counts, symptoms, spleen, et cetera. But also to see some early evidence of (technical difficulty) reduction, which we think it's an important measure of success. This is not going to be obviously a definitive data, but we want to have some evidence that a mutant-CALR antibody in patients with ET and MF can show some evidence of our reduction. So that will all be part of the update.

顯然，我們在過去幾個月中討論了該計劃的重要性，不僅僅是為了顯示對骨髓增生性腫瘤患者的傳統終點（如血球計數、症狀、脾臟等）的影響。但也看到了一些（技術難度）降低的早期證據，我們認為這是衡量成功的重要標準。這顯然不會是確鑿的數據，但我們希望有一些證據表明，ET 和 MF 患者的突變型 CALR 抗體可以顯示出一些減少的證據。這些都將成為更新的一部分。

617F, if you recall, started in the clinic later. We started dosing patients with MF in the third quarter of 2024. So it's a little bit behind. We intend to have an update this year. And the same point supply basically to that program. We would like to see impact, not only a traditional endpoint but some early evidence of a lead reduction in that program as well.

如果你還記得的話，617F 是後來才開始在診所工作的。我們將於 2024 年第三季開始為 MF 患者提供用藥。因此，它有點落後。我們打算今年進行更新。並且基本上為該計劃提供相同的點數。我們希望看到影響，不僅是傳統的終點，而且還有該計劃中鉛減少的一些早期證據。

Marc Frahm, TD Cowen.

馬克·弗拉姆（Marc Frahm），TD Cowen。

Hey, thanks for taking my questions. Maybe just a one nuance question on Stop-HS. Just Pablo, you mentioned earlier often these trials do have a little bit of a decline in treatment effect from Phase 2 to Phase 3. In HS specifically, we've seen kind of changes in antibiotic use and how that's treated with an SAP to maybe drive some of that effect. Can you remind us just how antibiotic use is being treated, what's treated in Phase 2 and how that may or may not differ in the Phase 3 trial?

嘿，謝謝你回答我的問題。也許這只是關於 Stop-HS 的一個細微問題。正如 Pablo 所說，您之前經常提到，這些試驗從第 2 階段到第 3 階段的治療效果確實會出現一些下降。具體來說，在 HS 中，我們看到了抗生素使用方面的變化以及如何使用 SAP 進行治療可能會產生一些影響。您能否提醒我們抗生素的治療方式、第 2 階段治療什麼以及第 3 期試驗中可能有何不同或相同之處？

And then for Christiana, on the absolute guidance, can you break down some of the assumptions there on US versus ex US growth, just given the kind of label changes that are happening, but also increasing reimbursement outside the US?

然後對於克里斯蒂安娜來說，關於絕對指導，您能否分解一些關於美國與美國以外地區增長的假設，考慮到正在發生的標籤變化，但美國以外的報銷也在增加？

So let me take the first part of the question. So first of all, the use of antibiotics in the Phase 3 was treated the same way that it was in the Phase 2. So let me just remind you what that is. Patients are not allowed to be on systemic antibiotics at study entry. Over the course of the study, if patients have started on systemic antibiotics or a flare, that's treated as a non-responder. Now if patients have started in the systemic antibiotic for a completely unrelated reason, that is not treated as a non-responder, and that's consistent with the Phase 2.

那麼就讓我來回答問題的第一部分。因此首先，第 3 階段的抗生素使用方式與第 2 階段相同。所以讓我提醒你那是什麼。患者在進入研究時不得使用全身性抗生素。在研究過程中，如果患者開始使用全身性抗生素治療或病情突然惡化，則視為對抗生素無反應。現在，如果患者因為完全不相關的原因開始使用全身性抗生素，那麼就不會被視為無反應者，這與第 2 階段一致。

In terms of the Opzelura guidance, the guidance that we have provided global, and it does reflect increased contribution from Europe. In 2024, the contribution was primarily driven by Germany and France. And in '25, we expect continued contribution from those two countries, but also now increased contribution from Italy and Spain. We are not going to be breaking down the guidance between the two regions.

就 Opzelura 指導而言，我們向全球提供了指導，它確實反映了歐洲貢獻的增加。2024年，貢獻主要來自德國和法國。在25年，我們預計這兩個國家將繼續做出貢獻，而且義大利和西班牙的貢獻也會增加。我們不會打破兩個地區之間的指導。

Kelly Shi, Jefferies.

傑富瑞 (Jefferies) 的 Kelly Shi。

Thank you for taking my questions. I have two. Firstly, can you share a little bit more color on [KRASG21D] program. In terms of POC data, what kind of like sample size and also tumor indications could we expect? And also based on the preclinical data achieved so far, do you think it hints any potential differentiation from other competitive G12D programs? And for Pablo, just quickly, I want to confirm, for the HiSCR75, 90 and 100, do you plan to show at a 12-week follow-up only or actually both 12 and 16 weeks follow-up?

感謝您回答我的問題。我有兩個。首先，您能否分享更多關於[KRASG21D]計劃的詳細資訊。就 POC 數據而言，我們可以預期什麼樣的樣本量以及腫瘤適應症？而且根據迄今為止獲得的臨床前數據，您是否認為它暗示了與其他競爭性 G12D 項目的任何潛在差異？對於 Pablo，我想快速確認一下，對於 HiSCR75、90 和 100，您是否計劃僅顯示 12 週的追蹤結果，還是實際上同時顯示 12 週和 16 週的追蹤結果？

Let me thank you, Kelly. So let me -- thank you, Kelly. So in terms of KRAS. The indications here as -- that have been the focus for us are pancreatic cancer and colorectal cancer. And specifically in pancreatic cancer, we're trying to accelerate enrollment because obviously, it has become a very competitive space. We're fully aware of what our competitors are doing. We believe, based on the profile here, that we have preclinically, which is a highly selective and potent G12D inhibitor, that if we accelerate this program, we can still compete in this space.

讓我謝謝你，凱利。所以請允許我--謝謝你，凱利。就 KRAS 而言。我們關注的重點是胰臟癌和大腸癌。特別是在胰臟癌領域，我們正試圖加快招募患者，因為顯然該領域的競爭非常激烈。我們完全清楚我們的競爭對手在做什麼。我們相信，基於此處的概況，我們在臨床前已研發出一種高選擇性和有效的 G12D 抑制劑，如果我們加速該項目，我們仍然可以在這個領域競爭。

Now it will come down, obviously, to the efficacy and safety that we see. But when we look at the data from our competitors, we think that particularly as you move to early lines of therapy in combination with chemotherapy, there's still space for a highly selective, well-tolerated G12D inhibitor. So we look forward to discussing data later this year, but that continues to be our view.

現在，顯然這取決於我們所看到的功效和安全性。但是，當我們查看競爭對手的數據時，我們認為，特別是當您轉向與化療相結合的早期治療方案時，高選擇性、耐受性良好的 G12D 抑制劑仍然有發展空間。因此，我們期待今年稍後討論數據，但這仍然是我們的觀點。

In terms of what we're going to disclose for the povo HS studies in terms of other endpoints, that's not a decision that we've made at this point. Obviously, we'll have to communicate the overall results of the study, as I answered a little bit earlier here. But whether we add a number of other endpoints or other release, we haven't decided.

關於我們將就 povo HS 研究的其他終點披露什麼內容，目前我們還沒有做出決定。顯然，我們必須傳達研究的整體結果，正如我之前在這裡回答的那樣。但我們尚未決定是否要添加其他端點或其他版本。

Brian Abrahams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

Hey, good morning. Thanks for taking my question. Maybe on the BET inhibitor, can you talk about the role you foresee for that in a post-Jakafi amount of therapy setting? And then what's your latest thinking on the frontline development path? What are you looking for out of the treatment that you've combo data to move forward? And are we still looking for results from that this year? Thanks.

嘿，早安。感謝您回答我的問題。也許關於 BET 抑制劑，您能談談您預見它在 Jakafi 後治療環境中的作用嗎？那麼您對於前沿發展路徑的最新想法是什麼？您希望從現有的組合數據中得到哪些治療來推動治療的進展？今年我們還在期待結果嗎？謝謝。

Certainly. So on the second line, look, I think that today, as we know, eventually, as good as Jakafi is for patients with myelofibrosis, eventually all patients progress and they need better treatment options when they progress. Obviously, in addition to the BET inhibitor, we're developing the mutant-CALR antibody in the V617F inhibitor.

當然。因此，在第二行，看，我認為今天，正如我們所知，最終，儘管 Jakafi 對骨髓纖維化患者有好處，但最終所有患者都會進展，並且在進展時他們需要更好的治療選擇。顯然，除了 BET 抑制劑之外，我們也正在開發 V617F 抑制劑中的突變型 CALR 抗體。

But in the relatively near term, we think that the BET inhibitor can provide a very good treatment options for patients with MF to progress after Jakafi. That's why we are accelerating that second line program as much as we can. And we disclosed the basic design at ASH, and you'll hear more of an update there this year.

但在相對較短的時間內，我們認為 BET 抑制劑可以為 Jakafi 後進展的 MF 患者提供非常好的治療選擇。這就是我們盡可能加快第二線計畫的原因。我們在 ASH 上揭露了基本設計，今年您將會聽到更多更新。

In terms of first-line indication for the BET inhibitor, what we need are more data. We need more clarity on the safety profile and the impact on endpoints that has a combination with Jakafi in previously untreated patients. We showed an update at ASH, which we think is very encouraging in terms of the ability to combine our BET inhibitor with Jakafi and the impact on spleen, symptoms and importantly, the impact that we saw in hemoglobin in the presentation that we gave at ASH. So we're still encouraged by the data. I think we need additional data to make that decision and to have another conversation with FDA on a potential first study.

對於BET抑制劑的第一線適應症而言，我們需要更多的數據。我們需要更清楚地了解安全性概況以及與 Jakafi 合併使用對先前未接受過治療的患者的終點影響。我們在 ASH 上展示了最新進展，我們認為這非常令人鼓舞，因為我們能夠將 BET 抑制劑與 Jakafi 結合起來，並對脾臟、症狀產生影響，更重要的是，我們在 ASH 上的報告中看到了對血紅蛋白的影響。因此我們仍然對數據感到鼓舞。我認為我們需要更多的數據來做出這個決定，並與 FDA 就潛在的首次研究進行另一次對話。

Jay Olson, Oppenheimer.

傑伊奧爾森、奧本海默。

Hey congrats on the quarter. For ruxolitinib XR -- also congrats on achieving bioequivalence. Can you just talk about your plans to commercialize rux XR and also the timeline for a fixed-dose combination with your BET inhibitor? Thank you.

嘿，恭喜本季。對於蘆可替尼 XR——也祝賀其實現生物等效性。您能談談將 rux XR 商業化的計劃以及與 BET 抑制劑固定劑量組合的時間表嗎？謝謝。

So maybe on the commercialization, I mean, the timeline is basically, we are now waiting for the end of the stability study to submit to FDA by the end of this year. So that will -- it's a response to a CRL. So it's a slightly different timelines, and we should be commercializing in 2026, which if you look at the window it gives us versus the 2029 first generic of twice a day is around 2.5 years. And obviously, the goal of that during that period is to have as many patients as possible being treated with once a day as a single agent as Jakafi is used today in most indications, in most patients.

所以也許就商業化而言，我的意思是，時間表基本上是，我們現在正在等待穩定性研究的結束，以便在今年年底前提交給 FDA。所以這是對 CRL 的回應。因此，這是一個略有不同的時間表，我們應該在 2026 年實現商業化，如果你看一下它給我們的時間窗口，與 2029 年相比，每天兩次的第一個仿製藥大約需要 2.5 年。顯然，在此期間我們的目標是讓盡可能多的患者每天接受一次單一藥物治療，因為如今 Jakafi 已用於大多數適應症和大多數患者。

Now related to the first-line study and the BET combination, obviously, the whole program depends on what Pablo was just speaking about, which is a profile of the first-line combination. And also, if you think about it, of how the rest of our portfolio in MPN is evolving with the CALR and the 617F. So none of that has been firmly decided yet, but that's probably going to be happening over the next year also on how we can put it in combination with our BET inhibitor.

現在涉及一線研究和 BET 組合，顯然，整個計劃取決於 Pablo 剛才所說的，即一線組合的概況。而且，如果你想的話，我們在 MPN 中的其他投資組合是如何隨著 CALR 和 617F 而發展的。所以這些都還未最終確定，但明年我們或許會研究如何將其與 BET 抑制劑結合。

Eric Schmidt, Cantor Fitzgerald.

艾瑞克·施密特、康托·費茲傑拉。

Great, thanks. Great. Two questions here. This is [Emma] on for Eric. The first one on povo and HS, you shared about the HiSCR50, 12 and 16 weeks. I guess in terms of HiSCR75 as well, could you share any ranges of what you think would be meaningful and competitive data there in the evolving landscape? And then the second question is on the tafasitamab first-line and DLBCL study? What do you see as meaningful data there over the (inaudible) arm?

太好了，謝謝。偉大的。這裡有兩個問題。這是 [Emma] 為 Eric 主持的。第一篇關於 povo 和 HS 的文章，您分享了有關 HiSCR50、12 和 16 週的內容。我想就 HiSCR75 而言，您能否分享一些您認為在不斷發展的環境中有意義且有競爭力的數據範圍？第二個問題是關於 tafasitamab 一線和 DLBCL 研究？您認為（聽不清楚）手臂上有哪些有意義的數據？

Okay. So on the first one, on povo and HS, I'm going to have to give a similar answer to what I've given earlier, which is, obviously, you want to see statistical significance for the primary endpoint. The key secondary endpoint, obviously, are not similarly powered, but there are important endpoints to show a clear difference with placebo.

好的。因此，對於第一個問題，關於 povo 和 HS，我將必須給出與我之前給出的類似的答案，也就是說，顯然，您希望看到主要終點的統計意義。顯然，關鍵的次要終點沒有類似的效力，但有重要的終點顯示出與安慰劑的明顯差異。

I don't think it's productive to really set a bar for what we have to clear. If you look at the data from the Phase 2 study with the 20% at week 12 and 13% placebo subtracted at week 16 for povo, I think those are really strong results in the context of prior data releases in patients with HS. So if we are in the vicinity of those results, I think that's going to be a very important contribution.

我認為，為我們必須完成的事情設定一個標準是沒有意義的。如果您查看第 2 階段研究的數據，其中第 12 週的 povo 為 20%，第 16 週的 povo 為 13%，我認為在 HS 患者先前發布的數據背景下，這些結果是非常強勁的。因此，如果我們接近這些結果，我認為這將是一個非常重要的貢獻。

There's a top line first line, the first-line DLBCL study, as you know, this is a curative setting. So even a small impact on the primary endpoint of the study, I think, could be really, really important. And if you look at recent benchmarks such as the Polivy data, which showed a modest impact on PFS, it still has led to a substantial adoption of that in frontline patients. So I think it's a very clear indication where modest improvements could lead to a potentially wide adoption because you're talking about potential curative therapy.

這是一項頂級的一線研究，即一線 DLBCL 研究，如您所知，這是一種治癒性環境。因此，我認為，即使對研究的主要終點產生很小的影響，也可能非常非常重要。如果你查看最近的基準，例如 Polivy 數據，它顯示出對 PFS 的適度影響，但仍然導致第一線患者大量採用該方法。所以我認為這是一個非常明確的跡象，表明適度的改進可能會導致廣泛的應用，因為你談論的是潛在的治癒療法。

Matt Phipps, William Blair.

馬特菲普斯、威廉布萊爾。

Yeah, thanks. Two for me. One, can you maybe just remind us on the learnings from the robust trial that were incorporated into front line where you think you can succeed when that trial fails? And then for the mutant-CALR program, is that just going to be monotherapy this year? Or could we also get some Jakafi combo? And can you remind us preclinically, if you saw any differential activity between type 1 versus type 2 mutations in CALR. Thank you.

是的，謝謝。對我來說是兩個。首先，您能否提醒我們從嚴格的試驗中學到的經驗教訓，這些經驗教訓已被運用到前線，您認為當試驗失敗時，您能夠取得成功嗎？那麼對於突變型 CALR 計畫來說，今年是否只是單一療法？或者我們也可以得到一些 Jakafi 組合嗎？您能否在臨床前提醒我們，您是否看到 CALR 中 1 型和 2 型突變之間存在任何差異活動。謝謝。

So in terms of the mutant-CALR antibody, we haven't really decided -- we have initiated a combination with Jakafi. The specific details are what we're going to disclose. We haven't really decided. But it's possible that we'll disclose some Jakafi combination data. It's an important part of the development plan.

因此，就突變型 CALR 抗體而言，我們還沒有真正決定——我們已經開始與 Jakafi 進行聯合治療。具體細節我們稍後會披露。我們還沒有真正決定。但我們可能會揭露一些 Jakafi 組合數據。這是發展計劃的重要組成部分。

As we've discussed previously, we don't necessarily commit to a combination development for the mutant-CALR antibody. But it's possible that because of the really rapid and strong impact of Jakafi in patient symptoms, particularly as you know, as well as other end points, a short induction with Jakafi combined with mutant-CALR and then a long-term maintenance therapy with mutant-CALR antibody could be a treatment paradigm, but none of that has been decided. We'll discuss the development plan, the future development plans for the mutant-CALR antibody when we do we disclose the data.

正如我們之前討論過的，我們不一定致力於突變型 CALR 抗體的共同開發。但由於 Jakafi 對患者症狀的影響非常迅速且強烈，特別是如您所知，以及其他終點，使用 Jakafi 聯合突變型 CALR 進行短期誘導，然後使用突變型 CALR 抗體進行長期維持治療可能是一種治療範例，但這些都還未確定。當我們揭露數據時，我們會討論開發計劃，突變型 CALR 抗體的未來開發計劃。

What we have disclosed into the type 1, type 2 is that these are -- these two types of mutations are very different in the structure in the gene. And what we've discussed previously was that the affinity for the antibody for type 1, the type 2 is pretty different. In terms of what we expect to see in the clinic, we'll discuss that when we have the data results, but it's possible that we have a different level of activity in patients with different types of mutations.

我們已經揭示了 1 型和 2 型，這兩類突變在基因結構上有很大差異。我們之前討論過，1 型和 2 型抗體的親和力非常不同。對於我們期望在臨床上看到的情況，我們將在獲得數據結果時進行討論，但不同類型的突變患者的活動水平可能會有所不同。

Andrew Berens, Leerink Partners.

Leerink Partners 的 Andrew Berens。

Hey, thanks. Congrats on the good quarter in 2024. A couple more on Jakafi XR. I don't think you commented on the Cmax. Just wondering how that would looked as increase the dose to Cmin. And is there anything else that's gating approval either in the stability studies?

嘿，謝謝。祝賀 2024 年取得了良好的業績。關於 Jakafi XR 的更多內容。我認為您沒有對 Cmax 發表評論。只是想知道當增加劑量至 Cmin 時會怎麼樣。在穩定性研究中，還有其他什麼因素會限制核准嗎？

So in terms of XR, so look, you cannot replicate the Cmax with a once-a-day formulation compared with twice-a-day formulation. The FDA understands that. And that was not the purpose of the study. So that, what you have -- what you have to meet is obviously the AUC you see at steady state and the Cmin at steady state. As we disclosed in the slide deck, both of those endpoints were met. They're only gating factors is the stability studies. As I mentioned in my prepared remarks, we have discussed the results of the study with FDA, and we have an agreement with them on the stability studies necessary for the resubmission for the response to the CRL, and we expect that, that will be done before the end of the year.

因此就 XR 而言，與每日兩次的配方相比，每日一次的配方無法複製 Cmax。FDA 了解這一點。但這並不是該研究的目的。因此，您所擁有的東西——您必須滿足的顯然是穩定狀態下的 AUC 和穩定狀態下的 Cmin。正如我們在幻燈片中披露的那樣，這兩個目標都已滿足。它們唯一的限制因素是穩定性研究。正如我在準備好的發言中提到的，我們已經與 FDA 討論了研究結果，並與他們就重新提交 CRL 答复所需的穩定性研究達成了協議，我們預計這將在年底之前完成。

Andy Chen, Wolf Research.

安迪陳 (Andy Chen)，沃爾夫研究公司。

Hey, thank you for taking the question. So on povo HS again, can you talk about specific protocol differences between your trial and other trials, especially from IL-17 antibodies? What have you learned from the trials? And what might you be doing differently to amplify your efficacy here? And then also in your base case scenario, are you expecting only the high dose to be approved or both doses?

嘿，謝謝你回答這個問題。那麼再次談到 povo HS，您能談談您的試驗與其他試驗之間的具體方案差異嗎，尤其是 IL-17 抗體？你從這些試驗中學到了什麼？您會採取哪些不同的措施來增強您的效力？那麼，在您的基本情境中，您是否預期只有高劑量會獲得批准，還是兩種劑量都會獲得批准？

Thank you.

謝謝。

So Andy, it's difficult to get into specific difference between studies because we don't have all the details of every protocol that's out there. We think that the design of the Phase 3 studies is consistent with the way our competitors are studying patients with hidradenitis suppurativa. We designed a Phase 3 to have a slightly high percentage of patients with Hurley III as opposed to Hurley II. That was an important point that we wanted to emphasize in order to reduce the placebo effect since it's harder in patients with more advanced disease. And that was an important point that we wanted to emphasize.

所以安迪，很難了解研究之間的具體差異，因為我們並不掌握現有的每種協議的全部細節。我們認為，第 3 期研究的設計與我們的競爭對手對化膿性汗腺炎患者進行研究的方式一致。在我們設計的第 3 階段，Hurley III 患者的比例略高於 Hurley II 患者的比例。這是我們想要強調的一點，目的是減少安慰劑效應，因為對於病情較嚴重的患者來說，安慰劑效應更難產生。這是我們想要強調的重點。

I think that there were a couple of things that we did as well as we were careful in selecting sites. We run a series of trainings with the sites, which was consistent with what we did in the Phase 2 to make sure that the way these patients are assessed by the investigators is consistent with what we did in Phase 2. So we try to replicate in Phase 3 as much as we did in Phase 2. And obviously, as I mentioned earlier, the primary endpoint we selected based on the Phase 2 data, I think that was an important lesson in order to really see how quickly we can provide benefit to patients with a week 12 improvement, which also was the best endpoint for us in our Phase 2 study.

我認為我們在選擇地點時也做了一些事情，並且非常謹慎。我們對各研究中心進行了一系列培訓，這與我們在第二階段所做的工作一致，以確保研究人員評估這些患者的方式與我們在第二階段所做的工作一致。因此，我們嘗試在第三階段盡可能複製我們在第二階段所做的工作。顯然，正如我之前提到的，我們根據第 2 階段數據選擇了主要終點，我認為這是一個重要的教訓，以便真正了解我們能夠多快為第 12 週改善的患者帶來益處，這也是我們第 2 階段研究中的最佳終點。

In terms of the dose, when we have the data, we'll discuss with FDA, obviously. Yes, it's possible that both doses are positive. We will lead to a broader label with different rates of doses, but we'll discuss that when we have the data with FDA.

至於劑量，當我們獲得數據時，我們顯然會與 FDA 進行討論。是的，兩劑疫苗都可能呈現陽性。我們將推出包含不同劑量的更廣泛的標籤，但我們將在獲得 FDA 的數據後進行討論。

Salim Syed, Mizuho.

瑞穗的薩利姆賽義德 (Salim Syed)。

Hi, thanks for taking our question. This is Eric on for Salim. So just looking at modeling Jakafi through 2025. Just wondering how we should think about the change, the growth versus 2024? And how we should think about that through the year? It's more loaded in first half, second half, anything like that?

您好，感謝您回答我們的問題。這是 Eric 代替 Salim 上場。因此，只需看一下 2025 年的 Jakafi 建模即可。只是想知道我們應該如何看待變化、與 2024 年相比的成長？那我們這一年該如何思考這個問題呢？前半部的內容更豐富，後半部的內容更豐富，還有類似的情況嗎？

Thank you.

謝謝。

So the guidance range that we provided implies a year-over-year growth of 5% to 7%. In terms of how to model it through the year, remember that Q1 always is the lowest quarter and lower than the prior quarter. And this is because of the reset of the deductibles at the beginning of the year, which on the commercial side, you would expect to continue to see this year. And even on the Medicare Part D, unless patients get to spread it through the course of the year, it will continue to have more of an impact in the first quarter of the year. So expect Q1 to be the lowest quarter and lower relative to Q4 of '24.

因此，我們提供的指導範圍意味著年增 5% 至 7%。對於如何全年建模而言，請​​記住，第一季始終是最低的季度，並且低於前一季。這是因為年初重新設定了免賠額，從商業方面來看，預計今年還會繼續看到這種情況。即使是聯邦醫療保險 D 部分，除非患者能夠在全年分期付款，否則它仍將在第一季產生更大的影響。因此，預計第一季將是最低的季度，並且相對於 24 年第四季而言更低。

Evan Seigerman, BMO Capital Markets.

埃文·塞格曼 (Evan Seigerman)，BMO 資本市場。

Hi guys, thank you so much for taking my questions. Two for me. Just walk me through some of the initial assumptions for the pediatric Opzelura launch? What does this initial uptake curve look like? And how much is factored into your guidance? And second, kind of a hypothetical here. Would you ever consider an adalimumab head-to-head trial in HS versus povo, given that you want to establish yourself as a systemic standard of care in this market. I'm just thinking if this is a biosimilar market, you're coming in as a branded, and it could help you kind of getting a leg up here.

大家好，非常感謝你們回答我的問題。對我來說是兩個。您能向我介紹一下針對兒科 Opzelura 上市的一些初步假設嗎？初始吸收曲線是什麼樣的？您的指導中考慮了多少因素？其次，這是一種假設。鑑於您想要成為這個市場的系統性護理標準，您是否會考慮在 HS 和 povo 中進行阿達木單抗的頭對頭試驗？我只是在想，如果這是一個生物相似藥市場，你以品牌商的身份進入，這可以幫助你在這裡獲得優勢。

Yeah, I'll take the ADP launch. We're very excited about the opportunity that we have there. to help these patients between 2 and 11 years old, also because the very vast majority of them are still uncontrolled and pretty much on steroidal therapies. Obviously, in the second half of the year, we will see the initial uptake from the indication contributed to our net sales. But overall, in terms of sizing at peak, we think that, that opportunity will represent anywhere around 10% or 15% of the total atopic dermatitis Opzelura business.

是的，我將參加 ADP 發射。我們對於在那裡擁有的機會感到非常興奮。幫助這些 2 歲至 11 歲的患者，因為其中絕大多數仍未控制並且仍在接受類固醇治療。顯然，在今年下半年，我們將看到該指標對我們的淨銷售額的初步貢獻。但總體而言，就高峰規模而言，我們認為，該機會將佔異位性皮膚炎 Opzelura 總業務的 10% 或 15% 左右。

Let me take the second one. We have not discussed in the past whether to conduct a head-to-head study with adalimumab. There's a couple of points there. First of all, we -- let's wait to see the data for the HS-1 -- for the HS studies that are coming. Once we have the data in hand, we'll make decisions about future development. The challenge with the data that has been reported in the past with Humira and when you discuss this between physicians, is that while the response that has been reported was high and which has not been replicated since the original study, the drug failure on Humira is relatively fast. Patients seem to progress. presents with HS seem to progress relatively quickly.

讓我選第二個。我們過去沒有討論過是否要與阿達木單抗進行頭對頭研究。這裡有幾點。首先，我們 — — 讓我們等待查看 HS-1 — — 即將進行的 HS 研究的數據。一旦我們掌握了數據，我們就會對未來的發展做出決策。過去有關 Humira 的報告數據以及醫生之間討論這個問題時面臨的挑戰是，雖然報告的反應很高，並且自最初的研究以來還沒有重複過，但 Humira 的藥物失效相對較快。病人的情況似乎有所改善。患有 HS 的患者似乎進展相對較快。

So this is one of the reasons why HS has become such an important market, such important indications for a number of companies because there's a fair amount of dissatisfaction with the data, with the results in the real world with Humira. So at this point, we haven't made a decision to go ahead to study future development in HS. We'll discuss it after we have the data.

因此，這就是為什麼 HS 成為如此重要的市場、對許多公司如此重要的適應症的原因之一，因為人們對 Humira 的實際數據和結果有相當多的不滿意。因此目前我們還沒有決定繼續研究 HS 的未來發展。獲得數據後我們將進行討論。

Ash Verma, UBS.

瑞銀的 Ash Verma。

Great, thanks for taking my question. Just one. So on povo and HS, I wanted to understand what is your view of the potential upcoming readouts from competitors? You have [LIMBER]. How would that impact your value proposition for povo in this market? Thanks.

太好了，感謝您回答我的問題。只有一個。因此，關於 povo 和 HS，我想了解您對競爭對手即將推出的潛在讀數有何看法？你有[柔軟精]這會對您對 povo 在這個市場的價值主張產生什麼影響？謝謝。

So at risk of being repetitive. So if we look at the Phase 2 data that we've reported in a number of places, both week 12, week 16, and the totality of the data across all the endpoints HiSCR50, 75, 90, 100 and pain response, we think we have a very competitive profile with povo. Assuming everybody has a certain level of correction from Phase 2 to Phase 3, we believe that when you put together all the efficacy data, together with the safety profile we saw in the Phase 2, that we have a very competitive profile with biologics and certainly with LIMBER.

因此有重複的風險。因此，如果我們查看我們在多個地方報告的第 2 階段數據，包括第 12 週、第 16 週以及所有終點 HiSCR50、75、90、100 和疼痛反應的全部數據，我們認為 povo 具有非常強的競爭力。假設每個人從第 2 階段到第 3 階段都有一定程度的矯正，我們相信，當你把所有的功效數據，加上我們在第 2 階段看到的安全性數據放在一起時，我們在生物製劑方面，當然還有 LIMBER 方面，都具有非常強的競爭力。

Kripa Devarakonda, Truist Securities.

Devarakonda 先生，Truist Securities 成員。

Hey guys, thank you so much for taking my question. On Jakafi, it think like PV is primarily driving growth. Can you talk about the patient population where you're getting uptake? And what the expectations are in terms of growth? Is it primarily through new patient adds or duration on therapy as well? And beyond rux XR and the V617F inhibitor, any additional life cycle management plans for your footprint in PV, which seems to be growing?

嘿夥計們，非常感謝你們回答我的問題。對 Jakafi 而言，其認為 PV 是推動成長的主要動力。您能談談您接受治療的患者族群嗎？對於成長有什麼預期？主要是增加新病人還是治療持續時間來增加？除了 rux XR 和 V617F 抑制劑之外，您在 PV 領域的足跡似乎正在不斷增長，還有其他什麼生命週期管理計劃嗎？

Yes, I can speak. I mean as you see, I mean, PV is -- of the three indication is the one that is growing the fastest. And it is driven by earlier treatment, and that's based on the data we have shown that by treating early, you can basically reduce the incidence of thrombosis.

是的，我會說話。正如您所看到的，PV 是這三個指標中成長最快的。這是由早期治療推動的，這是基於我們的數據，表明透過早期治療，基本上可以降低血栓形成的發生率。

So basically, help patients have a longer thrombosis-free survival. And that was the MAGIC study that we have been sharing with physicians over the past year, and it has been driving this adoption that we are seeing in PV as well as the change in the Medicare co-pay for the Medicare patient, which is also helping in PV.

所以從根本上來說，就是幫助患者延長無血栓存活期。這就是我們在過去一年中一直與醫生分享的 MAGIC 研究，它推動了我們在 PV 中看到的這種採用，以及醫療保險患者的醫療保險共同支付的變化，這也對 PV 有幫助。

So we, as we said in the prepared remarks, we think PV will become the largest of the three indications over time, driven by this new patient -- this new earlier patient flow and the duration of treatment we are observing in PV.

因此，正如我們在準備好的評論中所說的那樣，我們認為，隨著時間的推移，PV 將成為三種適應症中最大的一種，這受到這一新患者——這一新的早期患者流量以及我們在 PV 中觀察到的治療持續時間的推動。

Regarding the overall portfolio, obviously, the V617F, mutation is the course of 90% -- 80% to 90% of PV cases in the US. So that will be the key driver of the next generation of products for Incyte.

就整體情況而言，顯然 V617F 突變是美國 90%（80% 至 90%）的 PV 病例的病因。這將成為 Incyte 下一代產品的關鍵驅動力。

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

謝謝。我們的問答環節已經結束。我想將發言權轉回給大家，以便大家可以發表進一步的評論或結束語。

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

感謝大家今天參加電話會議，如果您有疑問，IR 團隊將在當天剩餘時間內為您提供後續跟進服務。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直播到此結束。此時您可以斷開您的線路，並享受美好的一天。我們感謝您今天的參與。