英賽德 (INCY) 2026 Q2 法說會逐字稿

Greetings, and welcome to the Incyte second quarter 2026 earnings conference call webcast. (Operator Instructions) As a reminder, this conference is being recorded. (Operator Instructions)

各位好，歡迎收看 Incyte 2026 年第二季財報電話會議網路直播。(接線員指示) 提醒各位，本次會議將被錄音。(接線員指示)

It’s now my pleasure to turn the call over to Alexis Smith, Vice President, Head of Investor Relations. Please go ahead, Alexis.

現在我很榮幸將電話會議交給投資人關係部副總裁暨主管 Alexis Smith。Alexis，請開始。

Thank you, and good morning. Welcome to Incyte's second quarter 2026 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.

謝謝，各位早安。歡迎參加 Incyte 2026 年第二季財報電話會議。在開始之前，我鼓勵大家前往我們網站的「投資人」專區，查閱新聞稿、相關財務表格，以及配合今日討論的簡報投影片。

On today's call, I'm joined by Bill, Pablo, and Suky, who will deliver our prepared remarks. Steven, Dave, and Mohamed will also be available for Q&A.

今天的電話會議上，我與 Bill、Pablo 及 Suky 一同出席，他們將發表我們事先準備的談話內容。Steven、Dave 與 Mohamed 也將出席以回答問答環節的問題。

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

我想提醒各位，我們將發表前瞻性陳述，這些陳述係基於我們目前的預期與信念。這些陳述受到若干風險與不確定性影響，我們的實際結果可能出現重大差異。我鼓勵各位參閱我們向 SEC 提交文件中所討論的風險因素，以取得更多細節。

I'll now hand the call over to Bill.

接下來我把電話交給 Bill。

Thank you, Alexis, and good morning, everyone. At the start of the year, we laid out a plan to move Incyte from reliance on a cornerstone product to a company with multiple growth drivers. Six months in, this transition is well underway, and we've made tangible progress. We've strengthened the core business, delivered key regulatory milestones, derisked and advanced our pipeline to late-stage development, and added a novel Phase 3 hematology asset through business development.

謝謝你，Alexis，各位早安。在年初，我們提出一項計畫，將 Incyte 從依賴單一基石產品，轉型為擁有多個成長動能的公司。半年過去，這項轉型已在順利推進，我們也取得了具體進展。我們強化了核心業務、達成關鍵法規里程碑、降低風險並推進我們的研發管線至後期開發階段，並透過商務開發新增一項新穎的第三期血液學資產。

Let me expand on each. First, our business continues to perform above expectations. Total net sales growth was driven by increased demand and higher net sales across every product. Jakafi remains foundational to the company and delivered another strong quarter. Keeping this product healthy is a strategic priority because it serves as a funding vehicle for the pipeline and new product launches.

我將逐一說明。首先，我們的業務表現持續優於預期。總淨銷售額成長來自需求增加，以及所有產品淨銷售額的提升。Jakafi 仍是公司的基礎，並再次交出強勁的一季表現。維持該產品的健康成長是策略重點，因為它是研發管線與新產品上市的資金來源。

At the same time, our core business, excluding Jakafi, continues to grow and is solidly on track to reach $3 billion to $4 billion in net sales by 2030. Importantly, this growth is not dependent on a single asset, but is supported by multiple products and near-term launches. We have the commercial capabilities, resources, infrastructure, and management team required to execute successfully. The opportunity here is not simply the value of each individual product, but our ability to launch and scale multiple products in parallel. This capability will be a key driver of Incyte's next phase of growth.

同時，我們的核心業務（不含 Jakafi）持續成長，並穩健朝著 2030 年淨銷售額達 30 億至 40 億美元的目標前進。重要的是，這項成長並不依賴單一資產，而是由多項產品與近期上市計畫所支撐。我們具備成功執行所需的商業能力、資源、基礎設施與管理團隊。此處的機會不僅在於每一項單一產品的價值，更在於我們能夠並行推出並擴大多項產品的能力。這項能力將成為 Incyte 下一階段成長的關鍵驅動力。

Second, we achieved several of the key regulatory milestones we identified at the beginning of the year, including the approval and launch of Jakafi XR as well as the positive CHMP opinion of Opzelura in moderate AD, with the final European Commission decision and signature expected in the third quarter. In addition, regulatory reviews for povorcitinib in HS and Monjuvi in first-line DLBCL are underway with anticipated approvals and launches through early 2027.

第二，我們達成了年初所設定的多項關鍵法規里程碑，包括 Jakafi XR 的核准與上市，以及 Opzelura 用於中度異位性皮膚炎（AD）的 CHMP 正面意見；預期最終歐盟執委會決議與簽署將於第三季完成。此外，povorcitinib 用於化膿性汗腺炎（HS）以及 Monjuvi 用於第一線瀰漫性大 B 細胞淋巴瘤（DLBCL）的法規審查正在進行中，預期核准與上市將延續至 2027 年初。

Third, we moved multiple assets into late-stage development. We launched Phase 3 studies for '989 and second-line ET, '734 in PDAC, and '890 in CRC. We also have a catalyst-rich second half of the year with 10 data readouts across nearly all assets in our clinical pipeline, including data from our registration trials for Opzelura in HS and povorcitinib in PN. As these programs advance, we are gaining greater visibility into the potential shape of our growth profile beyond 2029.

第三，我們將多項資產推進至後期開發。我們已啟動第三期研究：'989 用於第二線 ET、'734 用於胰臟導管腺癌（PDAC），以及 '890 用於大腸直腸癌（CRC）。今年下半年也將是催化劑密集的期間，我們臨床研發管線幾乎所有資產合計將有 10 項數據讀出，包括 Opzelura 用於 HS 以及 povorcitinib 用於結節性癢疹（PN）的註冊性試驗數據。隨著這些計畫推進，我們對 2029 年以後潛在成長輪廓的能見度也在提升。

We also strengthened our hematology portfolio through business development. The Vega transaction added latarcibart, a potentially transformative treatment for Von Willebrand's disease in Phase 3 development and a potential new growth driver for the company. Latarcibart expands our most important therapeutic franchise, offers an attractive risk-reward profile, and the transaction was structured to preserve balance sheet flexibility. It checked all the boxes we look for in business development and is a textbook example of a type of deal that makes sense for Incyte.

我們也透過商務開發強化了血液學產品組合。Vega 交易新增了 latarcibart，這是一項可能具變革性的 Von Willebrand 氏病治療，正處於第三期開發階段，並可能成為公司的新成長動能。Latarcibart 擴大了我們最重要的治療領域版圖，提供具吸引力的風險報酬特性，而該交易的設計也保留了資產負債表的彈性。它符合我們在商務開發中尋找的所有條件，是一個非常典型、也最適合 Incyte 的交易範例。

Taking together, Incyte is no longer dependent on one asset, catalyst, or blockbuster. We now have a solid core business, a series of near-term launches, and a more mature late-stage pipeline supporting multiple avenues for future growth. Operationally, we're a stronger organization than we were a year ago. Our focus right now is execution, turning Phase 3 studies into approvals and approvals into successful launches.

綜合來看，Incyte 已不再依賴單一資產、單一催化劑或單一重磅產品。我們現在擁有穩固的核心業務、一系列近期上市計畫，以及更成熟的後期研發管線，支撐多條未來成長路徑。在營運面，我們比一年前更為強健。我們目前的重點是執行力：將第三期研究轉化為核准，並將核准轉化為成功上市。

Turning to the quarter. Total revenue in the second quarter of '26 was $1.67 billion, up 38% year over year. Total net sales in the second quarter were $1.49 billion, representing 40% growth year over year. The increase was driven by continued demand across the portfolio and by a one-time non-cash benefit from the CMS settlement. Excluding this benefit, total net sales increased 17%. This growth was broad based, with every marketed product growing year over year in both the US and international markets.

接著談本季表現。2026 年第二季總營收為 16.7 億美元，年增 38%。第二季總淨銷售額為 14.9 億美元，年增 40%。成長來自產品組合持續的需求，以及 CMS 和解帶來的一次性非現金利益。若排除此項利益，總淨銷售額增加 17%。這項成長相當全面，我們所有已上市產品在美國與國際市場的年增率皆為正成長。

Jakafi sales in the second quarter were $817 million, up 7% year over year. Prescription demand for Jakafi increased 9% across all indications, MF, PV, and GVHD, with PV being the largest growth driver. New patient starts remain strong. The prescriber base is stable, and formulary coverage is broad, providing an important foundation for the Jakafi XR launch.

Jakafi 第二季銷售額為 8.17 億美元，年增 7%。Jakafi 在所有適應症（MF、PV 與 GVHD）的處方需求增加 9%，其中 PV 是最大的成長驅動因素。新病患起始用藥仍然強勁。開立處方的醫師基礎穩定，且給付名冊（formulary）涵蓋廣泛，為 Jakafi XR 的上市提供了重要基礎。

A few comments on XR. The launch has 2 parts: coverage and adoption. On coverage, we're on track to achieve our year-end formulary goal of 50% to 70%, supported by recent wins at ESI, CVS, Optum, and more than 10 regional plans.

關於 XR 補充幾點。上市包含兩個部分：給付涵蓋與採用。在給付涵蓋方面，我們正按計畫在年底達成 50% 至 70% 的給付名冊目標，近期已在 ESI、CVS、Optum 以及超過 10 個區域性方案取得進展。

On adoption, we expect physician adoption to build gradually through the remainder of 2026 as coverage expands and physicians gain experience with XR, with acceleration expected throughout 2027. Commercially, XR generated $10 million in sales in the second quarter, which primarily consists of initial inventory build. We expect XR sales to approach $40 million to $50 million for the full year, which is captured in our full year Jakafi guidance.

在採用方面，隨著給付涵蓋擴大、醫師對 XR 的使用經驗增加，我們預期醫師採用率將在 2026 年剩餘期間逐步提升，並在 2027 年加速。在商業表現上，XR 第二季貢獻 1,000 萬美元銷售額，主要來自初期庫存建立。我們預期 XR 全年銷售額將接近 4,000 萬至 5,000 萬美元，這已反映在我們全年 Jakafi 指引中。

Sales for our core business, excluding Jakafi, were $671 million, up 127% year over year. Excluding the onetime Opzelura benefit, sales grew 44%. This business is becoming an increasingly important part of how we transition Incyte through the LOE period and for long-term growth. Opzelura remains the largest contributor of our business outside of Jakafi, generating $450 million in second quarter sales. This includes $204 million of net product sales and a onetime non-cash benefit of $246 million related to our agreement with CMS and the reversal of previously accrued balances associated with the resolution of Medicaid rebate litigation.

我們的核心業務（不含 Jakafi）銷售額為 6.71 億美元，年增 127%。若排除 Opzelura 的一次性利益，銷售額成長 44%。這項業務正日益成為我們在專利到期（LOE）期間推動 Incyte 轉型，以及長期成長的重要組成。Opzelura 仍是 Jakafi 以外業務的最大貢獻者，第二季銷售額達 4.50 億美元。其中包含 2.04 億美元的產品淨銷售額，以及 2.46 億美元的一次性非現金利益，該利益與我們與 CMS 的協議，以及因 Medicaid 退費訴訟解決而回轉先前已提列的應計餘額相關。

In the US, sales, excluding the onetime benefit, were $161 million, an increase of 22% versus the second quarter of 2025. Demand here remains strong, with prescriptions increasing 26% year over year, which outpaced the overall market, which grew 21%. New patient starts also remained strong, with Opzelura capturing 46% of branded topical NBRx volume, a leading indicator of future growth and business health.

在美國，若排除一次性利益，銷售額為 1.61 億美元，較 2025 年第二季增加 22%。此處需求仍然強勁，處方量年增 26%，高於整體市場 21% 的成長。新病患起始用藥同樣維持強勁，Opzelura 取得品牌外用藥 NBRx 量的 46% 市占，這是未來成長與業務健康度的領先指標。

The resolution of the CMS matter improves the economics of the business, resulting in a favorable change to our average selling price and gross to net profile. It effectively offset some of the investment we made to expand and maintain formulary access at the beginning of the year. As a result, prescription growth should translate more efficiently into net sales growth going forward. That said, we continue to view the pricing and reimbursement environment is dynamic, and so maintaining broad access and a disciplined gross-to-net profile remains a priority.

CMS 事項的解決改善了業務的經濟效益，帶來我們平均售價以及毛額到淨額（gross-to-net）結構的有利變化。這有效抵消了我們在年初為擴大並維持處方集（formulary）可及性所投入的部分投資。因此，未來處方量成長應能更有效率地轉化為淨銷售額成長。儘管如此，我們仍認為定價與給付環境是動態的，因此維持廣泛可及性與嚴謹的毛額到淨額（gross-to-net）結構仍是優先事項。

Opzelura is in a stronger position today than it was a year ago. Demand is robust, and access is broad. And while we're encouraged by this momentum, this is not a business we can put on autopilot. Sustaining growth will require effective commercial execution and continued focus on the access and pricing dynamics that support growth.

Opzelura 目前的處境比一年前更為有利。需求強勁，可及性廣泛。儘管我們對這股動能感到鼓舞，但這不是一項可以自動運轉的業務。要維持成長，將需要有效的商業執行，以及持續聚焦於支撐成長的可及性與定價動態。

Internationally, Opzelura sales were $43 million in the second quarter, up 34% year over year. Growth remains robust in vitiligo, where we see strong demand across markets.

在國際市場方面，Opzelura 第二季銷售額為 4,300 萬美元，年增 34%。白斑症（vitiligo）領域的成長仍然強勁，我們在各市場都看到強勁需求。

We remain on track for potential approval and launch of Opzelura for moderate atopic dermatitis in Europe during the third quarter. We expect modest revenue contribution in 2026, with momentum building through '27 as additional countries launch and reimbursement expands. We continue to view the international expansion of Opzelura as an important long-term growth driver for the franchise with the potential to deliver 2 to 3 times the international sales today.

我們仍按計畫推進，Opzelura 用於治療歐洲中度異位性皮膚炎的潛在核准與上市有望在第三季實現。我們預期 2026 年的營收貢獻將較為溫和，並在 2027 年隨著更多國家上市及給付擴大而逐步累積動能。我們仍將 Opzelura 的國際擴張視為該產品線重要的長期成長驅動因素，具備將目前國際銷售額提升至 2 至 3 倍的潛力。

Finally, in hematology and oncology, net sales grew 69% to $222 million. Niktimvo, Monjuvi, and Zynyz were the biggest contributors to growth in the quarter. Niktimvo net sales were $60 million in the second quarter of '26, representing a 67% increase versus the prior year. The performance was entirely volume growth based, more than 300 new patients initiating therapy during the quarter and more than 1,200 patients treated. We currently hold approximately one-third of the third-line-plus market.

最後，在血液學與腫瘤領域，淨銷售額成長 69% 至 2.22 億美元。Niktimvo、Monjuvi 與 Zynyz 是本季成長的最大貢獻者。Niktimvo 在 2026 年第二季的淨銷售額為 6,000 萬美元，較去年同期成長 67%。此表現完全由銷量成長所驅動，本季有超過 300 名新病患開始治療，且治療病患總數超過 1,200 名。我們目前約占第三線以上市場的三分之一。

Monjuvi net sales were $54 million in the second quarter, up 72% year over year. Growth was primarily driven by uptake in follicular lymphoma and international markets, including the recent approval and launch in Japan in the second quarter.

Monjuvi 第二季淨銷售額為 5,400 萬美元，年增 72%。成長主要由濾泡性淋巴瘤的採用提升以及國際市場帶動，其中包括第二季在日本近期獲准並上市。

Monjuvi is expected to have three sources of growth, relapsed/refractory DLBCL, follicular lymphoma, and potentially, first-line DLBCL. We expect the existing indications to remain incremental contributors while first-line DLBCL has the potential to become the largest growth driver for the franchise over time.

Monjuvi 預期有三個成長來源：復發／難治性 DLBCL、濾泡性淋巴瘤，以及潛在的第一線 DLBCL。我們預期既有適應症將持續帶來增量貢獻，而第一線 DLBCL 隨時間推進有潛力成為該產品線最大的成長驅動因素。

Finally, Zynyz net sales were $50 million in the second quarter, a 4 times increase year over year with rapid and robust adoption in SCAC across markets. In the US, Zynyz is becoming the leading prescribed regimen with over 40% share in first-line SCAC in just 12 months post launch.

最後，Zynyz 第二季淨銷售額為 5,000 萬美元，年增 4 倍，且在各市場的 SCAC 適應症中快速且強勁地被採用。在美國，Zynyz 在上市後僅 12 個月內，即以超過 40% 的市占率成為第一線 SCAC 中處方量領先的治療方案。

Now I'll turn the call over to Pablo.

現在我把電話會議交給 Pablo。

Thank you, Bill, and good morning, everyone. At the beginning of 2026, we outlined ambitious development plans for the R&D organization, including four anticipated approvals, two new product launches, seven key data readouts, and the execution of 14 pivotal studies across our portfolio. As we have reached the midpoint of the year, I am happy to report that we have made significant progress and remain well positioned to deliver on the milestones we outlined.

謝謝你，Bill，各位早安。在 2026 年初，我們為研發（R&D）組織提出了具企圖心的開發計畫，包括預期四項核准、兩項新產品上市、七項關鍵數據讀出，以及在我們的產品組合中執行 14 項關鍵性（pivotal）研究。隨著我們來到年中的時間點，我很高興報告，我們已取得顯著進展，並且仍處於有利位置，可交付我們所提出的各項里程碑。

In the past 12 months, we have fundamentally changed the maturity of our portfolio, advancing multiple programs from early development into late-stage clinical trials while delivering regulatory submissions and approvals. Today, we have late-stage opportunities across all three of our core franchises, creating multiple opportunities for sustained long-term growth.

在過去 12 個月中，我們從根本上提升了產品組合的成熟度，推進多個計畫從早期開發進入後期臨床試驗，同時完成法規申請與取得核准。目前，我們在三大核心產品線皆擁有後期機會，創造多重可持續的長期成長機會。

All regulatory submissions, supporting our four anticipated approvals for 2026 are now complete. Jakafi XR was approved in the second quarter, representing the first of our two new product launches planned this year. In June, Opzelura received a positive CHMP opinion for the treatment of patients with moderate atopic dermatitis in Europe, with an approval anticipated in the third quarter. If approved, Opzelura would become the first topical JAK inhibitor treatment available in Europe for moderate AD.

支撐我們 2026 年預期四項核准的所有法規申請目前均已完成。Jakafi XR 已於第二季獲准，代表我們今年規劃的兩項新產品上市中的第一項。6 月，Opzelura 針對歐洲中度異位性皮膚炎患者治療獲得 CHMP 正面意見，預期於第三季取得核准。若獲核准，Opzelura 將成為歐洲首個可用於治療中度 AD 的外用 JAK 抑制劑。

Our submissions for povorcitinib in hidradenitis suppurativa and tafasitamab in newly diagnosed diffuse large B-cell lymphoma are under regulatory review with anticipated approvals and launches beginning later this year and into 2027.

我們針對化膿性汗腺炎（hidradenitis suppurativa）的 povorcitinib，以及針對新診斷瀰漫性大 B 細胞淋巴瘤的 tafasitamab 之申請，正處於法規審查中，預期核准與上市將自今年稍晚開始並延續至 2027 年。

Beyond our regulatory progress, we deliver multiple important data readouts across hematology, oncology, and dermatology, including registrational data for tafasitamab in first-line DLBCL and povorcitinib in vitiligo as well as additional data for '989 in essential thrombocythemia and myelofibrosis.

除了法規進展之外，我們也將在血液學、腫瘤學與皮膚科領域交付多項重要數據讀出，包括 tafasitamab 用於第一線 DLBCL 的註冊性數據、povorcitinib 用於白斑症的註冊性數據，以及 '989 在原發性血小板增多症與骨髓纖維化的額外數據。

At the same time, we expanded our late-stage pipeline with additional latarcibart and have advanced 13 of our now 15 planned pivotal studies, with the remaining two study initiations expected by year-end. Our teams continue to execute well against our development priorities, positioning the portfolio for both near-term value creation and long-term growth. Importantly, many of our highest value catalysts, including data readout and regulatory decisions remain ahead, positioning us for a catalyst-rich second half of the year.

同時，我們透過新增的 latarcibart 擴充了後期研發管線，並已推進目前規劃的 15 項關鍵性研究中的 13 項，其餘兩項預計在年底前啟動。我們的團隊持續良好執行開發優先事項，使產品組合同時具備短期價值創造與長期成長的定位。重要的是，我們許多最高價值的催化劑（包括數據讀出與法規決策）仍在前方，讓我們在下半年具備催化劑密集的布局。

With that, I'll now turn to the pipeline. Our hematology strategy combines leadership in established disease areas with first-in-class mutation directed therapies designed to redefine treatment across graft-versus-host disease, myeloproliferative neoplasms, and now bleeding disorders with additional latarcibart Von Willebrand's disease.

接下來我將談到研發管線。我們的血液學策略結合在既有疾病領域的領導地位，以及旨在重新定義治療的同類首創（first-in-class）突變導向療法，涵蓋移植物抗宿主病、骨髓增生性腫瘤，並且現在也延伸至出血性疾病，新增 latarcibart 用於馮·維勒布蘭德氏病。

In chronic graft-versus-host disease, we continue to advance axatilimab in two studies, evaluating its potential use earlier in the treatment paradigm, including in combination with ruxolitinib and in combination with steroids. We remain on track to share top line data from the Phase 2 study in combination with ruxolitinib in the second half of 2026.

在慢性移植物抗宿主病方面，我們持續推進 axatilimab 的兩項研究，評估其在治療流程中更早使用的潛力，包括與 ruxolitinib 聯合，以及與類固醇聯合。我們仍按計畫在 2026 年下半年分享與 ruxolitinib 聯合之第 2 期研究的主要（top-line）數據。

Top-line data from the Phase 3 study with steroids is expected in early 2028. We're also advancing a portfolio of molecularly targeted therapies for myeloproliferative neoplasms, or MPNs, focused on the underlying driver mutations of disease. Our MPN strategy is built around targeting the underlying biology of disease through highly selective therapies directed against key disease-driving mutations, CALR in JAK2V617F.

與類固醇聯合的第 3 期研究主要數據預計於 2028 年初公布。我們也在推進一系列針對骨髓增生性腫瘤（MPNs）的分子標靶療法組合，聚焦於疾病的驅動突變。我們的 MPN 策略建立在以高度選擇性的療法鎖定疾病的基礎生物學，針對關鍵致病突變，包括 CALR 與 JAK2V617F。

Our portfolio includes '989, our mutant CALR monoclonal antibody in late-stage development, '784, our CALRxCD3 bispecific in an ongoing Phase 1 trial, and next-generation programs in preclinical development. We continue to evaluate emerging data as these programs progress and prioritize those we believe have the strongest profiles and greatest potential for patients.

我們的產品組合包括：'989（處於後期開發的突變型 CALR 單株抗體）、'784（CALRxCD3 雙特異性抗體，正在進行第 1 期試驗），以及處於臨床前開發的次世代計畫。隨著這些計畫推進，我們持續評估新出現的數據，並優先投入我們認為具備最強特性與對病患最大潛力的項目。

As part of this assessment, we decided to discontinue development '058, our lead asset in our JAK2V617F targeted pipeline and are no longer expecting to report data later this year. Based on the totality of the data to date, we do not believe the molecule demonstrate the profile necessary to become a differentiated therapy. Importantly, this decision is specific to '058 and does not change our conviction in JAK2V617F as an important therapeutic target in MPNs.

作為此評估的一部分，我們決定停止開發 '058（我們 JAK2V617F 標靶研發管線中的主力資產），並且不再預期於今年稍晚公布相關數據。基於目前為止的整體數據，我們不認為該分子展現出成為具差異化療法所需的特性。重要的是，這項決定僅針對 '058，並不改變我們對 JAK2V617F 作為 MPNs 重要治療標靶的信心。

We are prioritizing our next-generation JAK2V617F targeted assets. We believe this next-generation programs provide a clear opportunity to realize the promise of electively targeting JAK2V617F. These programs are progressing through IND-enabling studies, and we'll plan to share more information, including preclinical data by the end of the year.

我們正優先推進我們的下一代 JAK2V617F 靶向資產。我們相信，這些下一代計畫提供了明確機會，可實現選擇性靶向 JAK2V617F 的承諾。這些計畫正推進至 IND 申請支援性研究階段，我們計畫在今年年底前分享更多資訊，包括臨床前數據。

Turning to our most advanced MPN program, '989, the first and only mutation specific therapy to enter late-stage development in CALR mutated MPNs. Early in the quarter, at the European Hematology Association Annual Meeting, we presented additional Phase 1 data in mutant CALR positive patients with ET and MF. As this data has matured, we continue to see evidence supporting the differentiated clinical profile of '989, strengthening our confidence in both the ongoing Phase 3 program and the broader development strategy in MF.

接著談我們最先進的 MPN 計畫 '989，這是首個且目前唯一進入 CALR 突變型 MPN 後期開發的突變特異性療法。本季初，在歐洲血液學協會（EHA）年會上，我們在 CALR 突變陽性的 ET 與 MF 患者中發表了更多第 1 期數據。隨著數據日益成熟，我們持續看到支持 '989 差異化臨床特徵的證據，進一步強化我們對正在進行的第 3 期計畫以及 MF 更廣泛開發策略的信心。

As mentioned earlier, our Phase 3 study is now underway in mutant CALR positive patients with ET who have received prior cytoreductive therapy. In MF, we remain on track to initiate a Phase 3 study in JAK-experienced patients in the second half of this year. We'll provide an update following the completion of regulatory discussions. Additionally, we continue to advance our Phase 1 cohort, evaluating '989 as a first-line treatment for patients with MF, both as monotherapy and in combination with ruxolitinib. We expect to share data from this cohort along with additional data from the JAK ineligible cohort previously presented at EHA later this year.

如先前所述，我們的第 3 期研究現已在曾接受細胞減量治療的 CALR 突變陽性 ET 患者中啟動。在 MF 方面，我們仍按計畫於今年下半年在曾使用 JAK 治療的患者中啟動第 3 期研究。待完成與監管機構的討論後，我們將提供最新進展。此外，我們也持續推進第 1 期隊列，評估 '989 作為 MF 患者的一線治療，包含單藥治療以及與 ruxolitinib 聯合治療。我們預期將於今年稍晚分享該隊列數據，並一併提供先前於 EHA 發表之不適用 JAK 治療隊列的更多數據。

We also continue to advance a subcutaneous formulation of '989 and initiate a Phase 1 study in mutant CALR positive patients in the second quarter. In addition to our ongoing efforts, we recently entered a global collaboration and license agreement with Halozyme to evaluate the subcutaneous formulation of '989 using ENHANZE technology. This collaboration complements our internal subcutaneous development efforts and provides additional flexibility as we optimize the administration profile of '989 for future commercial use.

我們也持續推進 '989 的皮下劑型，並於第二季在 CALR 突變陽性患者中啟動第 1 期研究。除我們既有的工作外，我們近期與 Halozyme 簽訂全球合作與授權協議，使用 ENHANZE 技術評估 '989 的皮下劑型。此合作可補強我們內部的皮下開發工作，並在我們為未來商業化使用優化 '989 的給藥特性時，提供額外彈性。

Earlier this month, we strengthened our hematology portfolio through the acquisition of Vega Therapeutics, adding latarcibart, a novel prognose modulator, in Phase 3 development for patients with Von Willebrand's disease to our late-stage pipeline.

本月稍早，我們透過收購 Vega Therapeutics 強化了血液學產品組合，將處於第 3 期開發、用於治療馮·維勒布蘭德氏病（Von Willebrand disease）的新型 prognose 調節劑 latarcibart 納入我們的後期研發管線。

At the International Society of Thrombosis and Hemostasis Congress earlier this month, data from the multi-dose VIVID-3 study evaluated latarcibart in patients with VWD were presented during a featured oral session. And VIVID-3, latarcibart demonstrated an 81% median reduction in annualized bleeding rate across patients with different Von Willebrand's disease subtypes and bleeding types along with a favorable tolerability profile.

在本月稍早舉行的國際血栓與止血學會（ISTH）大會上，多劑量 VIVID-3 研究中評估 latarcibart 用於 VWD 患者的數據，於重點口頭報告場次中發表。在 VIVID-3 中，latarcibart 在不同馮·維勒布蘭德氏病亞型與出血類型的患者中，年化出血率中位數降低 81%，且耐受性表現良好。

With once monthly subcutaneous dosing, latarcibart also has the potential to significantly reduce treatment burden compared with current prophylactic therapies, which are typically administered two to three times per week. Taken together, the efficacy tolerability and dosing profile, combined with its novel mechanism of action, give us confidence in the potential of latarcibart to establish a new standard of care.

採每月一次皮下注射給藥，latarcibart 亦有潛力相較於目前通常每週給藥兩到三次的預防性治療，顯著降低治療負擔。綜合其療效、耐受性與給藥特性，再加上其新穎作用機制，使我們對 latarcibart 有望建立新的照護標準充滿信心。

Our focus now is in advancing the Phase 3 VIVID-6 trial, and we remain on track to deliver top-line data by early 2029.

我們目前的重點是推進第 3 期 VIVID-6 試驗，並仍按計畫於 2029 年初公布主要（top-line）數據。

Turning to our oncology portfolio. All three of our lead solid tumor programs, '890, our TGFβR2xPD-1 bispecific antibody; '734, our KRASG12D inhibitor; and '667, our CDK2 inhibitor, are progressing through pivotal development, reflecting the continued maturation of our oncology pipeline. In parallel, we continue to generate data in robust Phase 1 programs, exploring the potential of this asset across different indications, lines of therapy, and combination settings, which will help inform broader development efforts.

接著談我們的腫瘤產品組合。我們三項領先的實體腫瘤計畫——'890（TGFβR2xPD-1 雙特異性抗體）、'734（KRASG12D 抑制劑）以及 '667（CDK2 抑制劑）——皆正推進至關鍵性開發階段，反映我們腫瘤研發管線持續成熟。同時，我們也持續在具規模的第 1 期計畫中產出數據，探索這些資產在不同適應症、治療線別與聯合治療情境下的潛力，以協助更廣泛的開發工作。

At the European Society for Medical Oncology Congress in October, we plan to present four rapid oral presentations, highlighting Phase 1 data across all three assets. This includes data '734 in first-line pancreatic and late-line colorectal, '890 in first line and late-line colorectal, and '667 in recurrent ovarian cancers. These presentations will represent the most comprehensive clinical update we have provided across our leading oncology programs and includes substantially larger and more mature data sets than we have previously shared, providing greater insight into the depth of the clinical efficacy and overall safety and helping further define the emerging competitive profile of each program.

在 10 月的歐洲腫瘤內科學會（ESMO）大會上，我們計畫發表四場快速口頭報告，重點呈現三項資產的第 1 期數據。其中包括：'734 於一線胰臟癌與後線結直腸癌、'890 於一線與後線結直腸癌，以及 '667 於復發性卵巢癌的數據。這些發表將是我們針對主要腫瘤計畫所提供最全面的臨床更新，所涵蓋的數據集較以往分享者更大且更成熟，可更深入了解臨床療效深度與整體安全性，並有助於進一步界定各計畫逐步成形的競爭定位。

For '890 and '734, the presentation will include data in combination with chemotherapy and in patient populations directly aligned with our ongoing Phase 3 studies. At the same time, the breadth of data across all three programs will help inform potential expansion into additional indications and treatment settings.

對於 '890 與 '734，發表內容將包含與化療聯合使用的數據，且患者族群與我們正在進行的第 3 期研究直接一致。同時，三項計畫的廣泛數據也將有助於評估擴展至其他適應症與治療情境的可能性。

Now I'd like to turn to our IAI portfolio, where we continue to build a dermatology franchise across both topical and systemic therapies with multiple opportunities for continued expansion. Regulatory and clinical efforts for ruxolitinib cream and povorcitinib continue to progress. We remain on track to report top-line results from our registrational Phase 3 program, evaluating ruxolitinib cream in mild to moderate HS by year-end. If positive, this data could support the first topical therapy specifically developed for patients with HS and would further expand Opzelura's role across inflammatory skin diseases.

接下來我想談我們的 IAI 產品組合；我們持續在外用與全身性治療兩方面建立皮膚科事業版圖，並具備多項可持續擴張的機會。ruxolitinib 乳膏與 povorcitinib 的法規與臨床工作持續推進。我們仍按計畫於年底前公布註冊性第 3 期計畫的主要結果，該研究評估 ruxolitinib 乳膏用於輕至中度 HS。若結果為正面，這些數據可望支持首個專為 HS 患者開發的外用療法，並進一步擴大 Opzelura 在發炎性皮膚疾病中的角色。

For povorcitinib, we continue to execute a broad development and regulatory strategy designed to support a multi-indication franchise. Povorcitinib is under review for the treatment of moderate to severe HS, and we expect potential approvals in Europe in late 2026 and in the US in the first quarter of 2027.

就 povorcitinib 而言，我們持續執行一項廣泛的開發與法規策略，旨在支持多適應症的產品版圖。povorcitinib 目前正接受審查，用於治療中重度 HS；我們預期可能於 2026 年底在歐洲獲准，並於 2027 年第一季在美國獲准。

In the first half of the year, we shared positive results from our Phase 3 program in vitiligo. Additionally, we remain on track to report top-line results from our Phase 3 program in prurigo nodularis in the fourth quarter. By year-end, we expect to have delivered six registrational study readouts for ruxolitinib cream and povorcitinib across HS, vitiligo, and PN, further strengthening our dermatology franchise spanning multiple diseases and treatment modalities.

今年上半年，我們分享了白斑症第 3 期計畫的正面結果。此外，我們仍按計畫於第四季公布結節性癢疹（prurigo nodularis）的第 3 期計畫主要結果。至年底前，我們預期將完成 ruxolitinib 乳膏與 povorcitinib 在 HS、白斑症與 PN 三項適應症上的六項註冊性研究讀出，進一步強化我們橫跨多種疾病與治療形式的皮膚科事業版圖。

To close, we continue to make meaningful progress across our pipeline in 2026, delivering important clinical and regulatory milestones. Our portfolio is broader, more mature, and increasingly diversified, and we expect an active second half of the year with multiple registrational data readouts, regulatory decisions, and development milestones across our three core franchises that we believe will further strengthen our long-term growth trajectory.

最後總結，我們在 2026 年持續於研發管線各方面取得實質進展，達成重要的臨床與法規里程碑。我們的產品組合更廣、更成熟且日益多元化；我們預期今年下半年將相當活躍，包含多項註冊性數據讀出、法規決策與開發里程碑，涵蓋我們三大核心事業版圖；我們相信這將進一步強化我們的長期成長軌跡。

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

接下來我把時間交給 Suky，請她就本季財務狀況進行更新。

Thanks, Pablo, and good morning, everyone. I'll begin with comments on our second quarter results and then turn to our updated full year outlook. As Bill mentioned earlier, total revenue in the second quarter was $1.67 billion, an increase of 38%, driven by strong product sales. Total net product sales were $1.490 billion, reflecting 40% growth versus the prior year. The increase was driven by strong product demand and a onetime non-cash benefit of $246 million. Excluding the onetime benefit, total net sales increased 17% versus the prior year.

謝謝你，Pablo，各位早安。我將先就我們第二季的業績發表評論，接著說明我們更新後的全年展望。如 Bill 先前提到，第二季總營收為 16.7 億美元，年增 38%，主要由強勁的產品銷售所帶動。產品淨銷售總額為 14.90 億美元，較去年同期成長 40%。成長動能來自強勁的產品需求，以及一次性 2.46 億美元的非現金收益。若排除該一次性收益，產品淨銷售總額較去年同期增加 17%。

Total GAAP expenses for the quarter were $976 million, an increase of 42% compared to the prior year. The year-over-year increase result reflects a lower expense base in the second quarter of 2025, resulting from the Novartis settlement of $242 million. When we exclude the favorable adjustment in the second quarter of 2025, total operating expenses grew 5%.

本季 GAAP 總費用為 9.76 億美元，較去年同期增加 42%。年增幅反映 2025 年第二季費用基期較低，係因諾華（Novartis）2.42 億美元和解所致。若排除 2025 年第二季的有利調整，總營業費用成長 5%。

GAAP cost of goods was $105 million, representing 7% of total net sales. This is in line with our expectations, and we expect COGS to be between 8% to 9% for the full year. Our GAAP R&D expenses were $517 million, an increase of 4%, driven by continued investment in our late-stage development assets across hematology and oncology.

GAAP 銷貨成本為 1.05 億美元，占總淨銷售額的 7%。這符合我們的預期，我們預期全年 COGS 將介於 8% 至 9%。我們的 GAAP 研發費用為 5.17 億美元，增加 4%，主要由於我們持續投資於血液學與腫瘤領域的後期開發資產。

Moving to GAAP SG&A. Expenses were $352 million, increasing 6% driven by prelaunch activities for povorcitinib. We ended the quarter with $4.5 billion in cash and cash equivalents. This excludes the close of the Vega Therapeutics acquisition in July, which I'll provide more color on momentarily.

接著談 GAAP 銷售、一般及行政（SG&A）。費用為 3.52 億美元，增加 6%，主要由 povorcitinib 上市前活動所帶動。本季末我們持有 45 億美元的現金及約當現金。此數字不包含 7 月完成的 Vega Therapeutics 收購案，我稍後會提供更多說明。

Now turning to our outlook for the remainder of the year. We are updating several components of our existing guidance for the full year, including total net sales, which is driven by guidance updates to Opzelura as well as hematology and oncology in R&D and SG&A operating expenses driven by the close of the Vega acquisition and related incremental cost in the second half of the year.

現在轉向我們對今年剩餘期間的展望。我們正在更新既有的全年指引中的數個項目，包括總淨銷售額；其變動係由 Opzelura 指引更新所驅動，並且因 Vega 收購完成及下半年相關增量成本，帶動血液學與腫瘤領域的研發與 SG&A 營業費用調整。

Starting with net sales. We are raising our full year 2026 total net sales guidance to $5.130 billion to $5.260 billion. For Opzelura, we are updating full year 2026 net sales guidance to $1.050 billion to $1.100 billion. Our new guidance reflects the previous guidance of $750 million to $790 million and the incremental estimated impact of $300 million to $310 million of net sales related to the CMS settlement.

先從淨銷售額開始。我們將 2026 年全年總淨銷售額指引上調至 51.30 億至 52.60 億美元。就 Opzelura 而言，我們將 2026 年全年淨銷售額指引更新為 10.50 億至 11.00 億美元。新指引反映先前 7.50 億至 7.90 億美元的指引，以及與 CMS 和解相關、估計增加 3.00 億至 3.10 億美元淨銷售額的增量影響。

This impact includes two key components, versus a onetime non-cash benefit of $246 million related to Opzelura net sales that was recorded in the second quarter. As a reminder, this amount is associated with the reversal of previously established accrual balances through the first quarter of 2026.

相較之下，該影響包含兩個關鍵組成部分；而第二季已認列一筆與 Opzelura 淨銷售額相關、一次性的 2.46 億美元非現金利益。提醒一下，該金額與截至 2026 年第一季先前已建立之應計餘額的回轉有關。

Second, higher net sales from an improved gross-to-net profile in the second quarter through the fourth quarter. In the second quarter, the impact of US Opzelura net sales was $15 million. This is a net impact after consideration of certain onetime prior year state-related liabilities that became effective at the conclusion of the CMS settlement. On a go-forward basis, we expect the impact to be approximately $40 million to $50 million for the second half of the year.

第二，第二季至第四季因毛利到淨額（gross-to-net）結構改善而帶來較高的淨銷售額。在第二季，美國 Opzelura 淨銷售額的影響為 1,500 萬美元。這是在考量若干一次性、前一年度與州相關的負債（於 CMS 和解完成時生效）後的淨影響。展望未來，我們預期下半年影響約為 4,000 萬至 5,000 萬美元。

Regarding our hematology and oncology portfolio, we are narrowing and raising full year guidance range to $860 million to $890 million based on strong performance in the first half of the year.

關於我們的血液學與腫瘤產品組合，基於上半年強勁表現，我們將全年指引區間收斂並上調至 8.60 億至 8.90 億美元。

Turning to operating expenses. We are updating our full year 2026 operating expense guidance. We are narrowing and raising our 2026 GAAP R&D and SG&A operating expense guidance to $4.915 billion to $4.995 billion. We're also raising total non-GAAP R&D and SG&A operating expenses to $4.625 billion to $4.695 billion. The new guidance reflects an increase of approximately $1.270 billion related to the upfront payment for in-process research and development and associated transaction costs, in tandem with approximately $50 million in ongoing Phase 3 development of latarcibart in Von Willebrand's disease.

接著談營業費用。我們正在更新 2026 年全年營業費用指引。我們將 2026 年 GAAP 研發與 SG&A 營業費用指引區間收斂並上調至 49.15 億至 49.95 億美元。我們也將非 GAAP 研發與 SG&A 營業費用總額上調至 46.25 億至 46.95 億美元。新指引反映約 12.70 億美元的增加，與在研研發（IPR&D）預付款及相關交易成本有關，同時也包含約 5,000 萬美元用於 latarcibart 在馮·維勒布蘭德氏病（Von Willebrand's disease）之第三期持續開發。

To close, we are pleased with our performance for the quarter and for the first half of the year and remain confident in our outlook.

最後，我們對本季以及上半年表現感到滿意，並對我們的展望仍具信心。

With that, I'll turn the call back over to the operator for Q&A.

接下來我把電話交回給接線員進行問答。

(Operator Instructions) Marc Frahm, TD Cowen.

(接線員指示) TD Cowen 的 Marc Frahm。

Congrats on the strong quarter commercially. Maybe this is mostly for Pablo. Just on the kind of CALR program and your regulatory discussions, can you maybe just review kind of what the major questions are still kind of awaiting resolution on that trial design in MF? How much of that is the endpoint, whether you can include something like anemia and some sort of composite versus how much of that is still outstanding dose selection work for particularly the type 2s and might, on that latter part, that take a little bit longer for type 1s versus type 2s and lead to kind of different trial initiation timelines?

恭喜商業面繳出強勁的一季。這題可能主要想問 Pablo。關於 CALR 計畫以及你們與主管機關的討論，能否回顧一下在 MF 試驗設計上，目前仍有哪些主要問題尚待釐清？其中有多少是關於終點，例如是否能納入像貧血以及某種複合終點；又有多少仍是劑量選擇工作尚未完成，特別是針對第 2 型？另外就後者而言，是否第 1 型相較第 2 型可能需要更久，進而導致不同的試驗啟動時程？

Thank you for the question. So when we think about the regulatory path in MF, there's basically two paths, right? One would be the standard, which I think we'll know about, which would include, SVR35 and TSS50 as end points or an alternative one, which will include other endpoints.

謝謝你的提問。當我們思考 MF 的法規路徑時，基本上有兩條路徑，對吧？一條是標準路徑，我想我們會知道其內容，會包含以 SVR35 與 TSS50 作為終點；另一條替代路徑則會納入其他終點。

Let me spend a minute on why we think the second is important to discuss with FDA. We thought and still think it's important to discuss with FDA. 99% is a complete novel mechanism of action, as we all know. And on top of delivering benefit -- as we saw the EHA data update that we provided, on top of delivering benefit on SVR35 and TSS50, it delivers an extraordinary benefit on improving hemoglobin levels in these patients. Most of the patients treated, whether it's first or second line MF show increases in hemoglobin that are clinically significant.

我花一點時間說明為什麼我們認為與 FDA 討論第二條路徑很重要。我們認為、也仍然認為與 FDA 討論很重要。正如大家所知，'989 的作用機轉有 99% 是全新的。而且除了帶來效益——如同我們提供的 EHA 數據更新所見——除了在 SVR35 與 TSS50 上帶來效益之外，它也在改善這些患者的血紅素水準方面帶來非常顯著的效益。大多數接受治療的患者，不論是一線或二線 MF，都出現具臨床意義的血紅素上升。

In addition to that, there's clear evidence of what we discussed as disease-modifying evidence, including reduction of malignant (inaudible) in bone marrow, reduction of malignant progenitors in peripheral blood, et cetera. So when you put all that together, we thought and still believe it's important to have a constructive dialogue with the FDA to see how we can incorporate some of these endpoints that reflect the benefit patients received from '989 and that reflect the mechanism of action '989 that they need to be reflected in the clinical trial design.

此外，也有明確證據支持我們所說的疾病修飾（disease-modifying）證據，包括骨髓中惡性（聽不清）減少、周邊血中惡性前驅細胞減少等等。因此，綜合以上，我們過去認為、現在也仍相信，與 FDA 進行具建設性的對話很重要，以了解如何將部分反映患者從 '989 獲得之效益、並反映 '989 作用機轉的終點納入臨床試驗設計中。

We have initiated these conversations with FDA. They're going well. They'd be constructive. And as soon as we complete those, we will give you clarity on what the regulatory path will be first- and second-line MF, which we intend to start this year, and then as a result of that, we'll continue the conversation with the agency on first-line MF, which we will initiate next year.

我們已啟動與 FDA 的這些對話。進展良好。也很具建設性。一旦完成，我們將就一線與二線 MF 的法規路徑提供更清楚的說明；我們計畫今年啟動相關試驗，並在此基礎上，持續與主管機關就一線 MF 進行討論，我們將於明年啟動。

At this point, our intention is to conduct a study in MF in all comers, type 1 and non-type 1 patients. potentially with the differential dosing strategy, not quite like ET because in ET, we have a dose escalation. The rapid normalization of platelets allows it for a rapid dose escalation. In MF, we would start type 1 and non-type 1 patients at two different dose levels instead of doing the dose escalation. But that's where we are today with the planning of the study.

目前，我們的意圖是在 MF 進行一項涵蓋所有受試者的研究，包括第 1 型與非第 1 型患者，可能採用差異化劑量策略；但不會完全像 ET，因為在 ET 我們會進行劑量遞增。血小板的快速正常化使得可以快速劑量遞增。在 MF 中，我們會讓第 1 型與非第 1 型患者以兩個不同的起始劑量水準開始，而不是進行劑量遞增。這就是我們目前在研究規劃上的進度。

Eric Schmidt, Cantor Fitzgerald.

Cantor Fitzgerald 的 Eric Schmidt。

Maybe a higher-level strategic question for Bill and team. Given you -- just on the Vega acquisition, how are you feeling about the breadth and depth of your pipeline? Do you have more capacity? And is there some sort of a target R&D as a percent of sales level that you might want to be spending at as we go into the Jakafi exploration?

我想對 Bill 與團隊提一個較高層次的策略問題。就 Vega 收購案而言，你們對管線的廣度與深度感受如何？你們是否還有更多產能／資源容量？另外，當我們進入 Jakafi 的探索階段時，你們是否有一個希望投入的研發費用占銷售額比例目標？

Yeah, it's a good question, Eric. A couple of things. As it relates to business development and frankly, R&D, our job is to keep this product line and pipeline moving. And so I think you can never underestimate attrition in any business.

是的，Eric，這是個好問題。有幾點。就業務開發以及坦白說研發而言，我們的工作是讓這條產品線與研發管線持續推進。因此，我認為你永遠不能低估任何業務中的流失率。

And so we are actively looking at potential opportunities that meet or check the same criteria that Vega did. And I think that we have a very clear framework for doing business development. When we see opportunities that meet certain strategic and financial criteria, we can act quickly. Alternatively, if we don't, we're comfortable being patient.

因此，我們正積極尋找符合或能勾選與Vega相同標準的潛在機會。而且我認為我們在業務開發方面有非常清晰的框架。當我們看到符合特定策略與財務標準的機會時，我們可以迅速採取行動。相反地，如果沒有，我們也願意耐心等待。

As it relates to R&D as a percentage of sales, I'd make a couple of comments there. We're not pursuing growth one at all costs. Alternatively, or on the other hand, we're not solving right now for a fixed margin percentage. What I will tell you is if there's any margin compression in this business, let's say, as we get to 2029, there'll have to be a clear and positive correlation with materially increasing the risk-adjusted value of our pipeline. And right now, every line item in our P&L is either absorbing, offsetting, or directly funding the growth strategy.

至於研發占銷售額的比例，我想在這裡補充幾點。我們並不是不計代價地追求成長。另一方面，我們目前也不是以固定的毛利率百分比為目標來做決策。我可以告訴你的是，如果這項業務出現任何利潤率壓縮——例如到2029年——那就必須與我們研發管線風險調整後價值的實質提升，呈現清楚且正向的相關性。而目前，我們損益表中的每一個科目，不是正在吸收、抵銷，就是在直接資助成長策略。

As you know, in SG&A, we're funding product launches. And as it relates to R&D, 80% of our investment is concentrated on what we think are really smart investments. And if any of the investments that we're making, if the facts and circumstances around those investments change or performance is not what we are expected, we stop making those investments. And as we get closer and we have more clarity on our pipeline, I think we're set up very well right now.

如你所知，在SG&A方面，我們正在為產品上市提供資金。而就研發而言，我們80%的投資集中在我們認為非常明智的投資上。如果我們正在進行的任何投資，其相關事實與情況發生變化，或表現不如預期，我們就會停止投入。隨著我們更接近並對研發管線有更清晰的掌握，我認為我們目前的布局非常到位。

I think when you look at the pipeline, there's four assets that have a high PTRS and the potential to deliver outsized returns. That's povorcitinib, '989, G12D, and VGA039. Now that's not to say that there's not value in TGFβxPD-1 or CDK2. But the four assets I just mentioned have the potential to move Incyte way beyond Jakafi, which is ultimately what we're solving for.

我認為當你看研發管線時，有四個資產具有很高的PTRS，並且有潛力帶來超額回報。那就是povorcitinib、'989、G12D，以及VGA039。這並不是說TGFβxPD-1或CDK2沒有價值。但我剛提到的四個資產，有潛力讓Incyte遠遠超越Jakafi，而這最終正是我們要解決的核心。

And so to wrap it up, 12 months of margin compression to set up 10 years of revenue and earnings growth, I think, is a smart calculation, and that's what we look at every day.

因此總結來說，用12個月的利潤率壓縮來換取10年的營收與獲利成長，我認為這是一個明智的計算，而這也是我們每天都在評估的事情。

Tazeen Ahmad, Bank of America.

Tazeen Ahmad，美國銀行。

I wanted to maybe ask one quick one about the announcement in the last week about your global collaboration with Halozyme to use their ENHANZE drug delivery technology to help with '989. Can you maybe give us a little bit more color on what exactly you'd like to improve and when you think this could move into a clinic and we could start to see data using this technology?

我想快速問一個問題，關於你們上週宣布與Halozyme的全球合作，使用他們的ENHANZE藥物遞送技術來協助'989。你們能否再多提供一些細節，具體希望改善哪些方面，以及你們認為這何時可能進入臨床，讓我們開始看到使用這項技術的數據？

Thanks, Tazeen. Pablo, why don't you set up where we are the program overall and then get into Halozyme?

謝謝你，Tazeen。Pablo，你先說明一下整體專案目前的進展，然後再談Halozyme，好嗎？

Certainly. I think -- let me remind you a couple of points that we made, which are really important about this program and the subcu development. We have completed a healthy volunteer work, and we are right now with the subcu existing subcu formulation in patients with MPNs. That's the status of the program.

當然。我想——先提醒大家幾個我們提過、對這個專案與皮下（subcu）開發非常重要的要點。我們已完成健康受試者研究，目前正使用既有的皮下配方，在MPN患者中進行研究。這就是該專案目前的狀態。

We have a clear path here to continue that program forward and by optimizing the existing formulation and the existing subcutaneous device for infusion, which is not wearable. As we discussed before, this is something that patients will have to apply for 15 to 20 minutes every other week to deliver the desired dose. That path is clear. We have discussions with FDA on a bridging strategy for that path that I just described.

我們有一條清晰的路徑可以持續推進該專案：透過優化既有配方，以及既有用於輸注的皮下注射裝置（非穿戴式）。如我們先前討論，患者需要每兩週使用一次，每次15到20分鐘，以輸送所需劑量。這條路徑很明確。針對我剛描述的路徑，我們也已與FDA就橋接策略進行討論。

We thought it was important to continue to add optionality to this program. As you can imagine, the conversations with Halozyme have been going on for quite some time before signature of the agreement. And they're not related in any way to any data that has emerged from the ongoing subcutaneous development. We thought it was important to have an additional option to improve flexibility and potentially to improve the patient experience when it comes to subcutaneous formulation and administration of '989.

我們認為持續為這個專案增加選擇性（optionalitiy）很重要。如你所想像，在簽署協議之前，我們與Halozyme的對話已進行了相當長一段時間。而且這些對話與目前進行中的皮下開發所產生的任何數據，沒有任何關聯。我們認為，針對'989的皮下配方與給藥方式，增加一個額外選項以提升彈性，並可能改善患者體驗，是很重要的。

So that's basically the plan we have in place. We're executing on the existing subcu plan with existing formulation, and we're adding another option now with the ENHANZE technology.

所以這基本上就是我們目前的計畫。我們會依照既有配方執行現有的皮下計畫，同時現在也透過ENHANZE技術新增另一個選項。

Faisal Khurshid, Jefferies.

Faisal Khurshid，Jefferies。

Can you set expectations for the G12D update that you're going to have at ESMO? And can you possibly give us some more perspective on how you think about competitive positioning and how you see your opportunity to differentiate within the class?

你們能否為即將在ESMO提供的G12D更新設定一下市場預期？另外，你們能否再多分享一些你們如何看待競爭定位，以及你們認為在同類藥物中有哪些差異化機會？

Great. Pablo, do you want to take the first part of the question?

好的。Pablo，你要先回答問題的第一部分嗎？

Certainly. Thank you for the question. So when we think about '734, our G12D inhibitor, I think we are convinced we have in our hands a highly selective, highly potent novel medicine that combines well with existing standard of care, which is in first-line pancreatic cancer is chemotherapy, either FOLFIRINOX or Genmab.

當然。謝謝你的提問。因此，當我們談到'734——我們的G12D抑制劑——我們相信我們手上的是一款高度選擇性、效力很強的創新藥物，且能與既有標準治療良好併用；在一線胰臟癌治療中，標準治療是化療，包含FOLFIRINOX或Genmab。

In that context, when we think about the development plan, our goal was to accelerate as much as possible development in first-line pancreatic cancer in combination with those two chemotherapy regimens. What we will do at ESMO is provide approximately 50 patients' worth of data half and half with Genmab and FOLFIRINOX with a fair amount of maturity, showing you where we are on efficacy and safety in that context. We think that's a really important derisking for the first-line pancreatic cancer strategy that we're pursuing.

在此背景下，當我們思考開發計畫時，我們的目標是盡可能加速在一線胰臟癌、與這兩種化療方案併用的開發。我們在ESMO將提供約50位患者的數據，其中一半使用Genmab、一半使用FOLFIRINOX，且數據成熟度相當不錯，向各位展示在該情境下的療效與安全性進展。我們認為，這對我們正在推進的一線胰臟癌策略而言，是非常重要的去風險（derisking）。

Now the first -- the Phase 3 study in first-line pancreatic cancer is ongoing. As far as we know, based on public disclosures, we are neck to neck with our competitors. We don't think we're behind. And our team is executing on that as fast as possible.

目前，一線胰臟癌的第3期研究正在進行中。就我們所知，根據公開揭露資訊，我們與競爭對手幾乎並駕齊驅。我們不認為自己落後。而我們的團隊正以最快速度推進執行。

Now let me add a little bit more context on the program because I think it's important, the breadth of how we're looking at this program in other indications. We're going to present data as well at ESMO of combination in colorectal cancer. We think that is a really important indication for G12D inhibitor. There's two basic ways to do it is late line in combination with EGFR inhibitors and in early lines in combination with chemotherapy and EGFR inhibitors. We'll show some of that data as well at the ESMO meeting.

另外我想再補充一些關於此專案的背景，因為我認為很重要：我們如何在其他適應症上以更廣的角度看待這個專案。我們也會在ESMO發表在大腸直腸癌的併用數據。我們認為這對G12D抑制劑而言是非常重要的適應症。基本上有兩種做法：一是在後線治療中與EGFR抑制劑併用；二是在較早線別與化療及EGFR抑制劑併用。我們也會在ESMO會議上展示其中部分數據。

So when you start thinking about our G12D program, if things go well and the data that we present continues to derisk the program, you should think about it in a number of different -- a couple of different tumor types and in a couple of different lines of therapy, specifically in pancreatic cancer in first-line in combination with chemotherapy and potentially in the adjuvant setting as well and in colorectal cancer in late line in combination with EGFR inhibitors and potentially in earlier lines in combination with chemotherapy and EGFR inhibitors.

因此，當你開始思考我們的G12D專案時，如果進展順利，且我們所呈現的數據持續為該專案去風險，你應該從幾個不同面向來看：涵蓋幾種不同腫瘤類型，以及幾個不同治療線別；具體而言，在胰臟癌的一線與化療併用，並且可能也包括輔助治療（adjuvant）情境；以及在大腸直腸癌的後線與EGFR抑制劑併用，並可能在較早線別與化療及EGFR抑制劑併用。

So we'll talk about it at ESMO. We think the data we're going to present is a significant derisking event for this program in first-line pancreatic and potentially in colorectal cancer as well. Thank you for the question.

所以我們會在 ESMO 上討論。我們認為我們將要呈現的數據，對於此計畫在一線胰臟癌、以及潛在在大腸直腸癌上的風險降低，是一個重大的去風險事件。謝謝你的提問。

I would just add to what Pablo said as it relates to competitive positioning, I think it's unlikely that pancreatic cancer becomes a winner-take-all market. You rarely see that in oncology. I think, generally speaking, oncologists resist dependence on a single treatment. And so this is not, I believe, in either/or calculation. Populations are different. There's various combination strategies that can be put in place.

我只想補充 Pablo 關於競爭定位的看法，我認為胰臟癌不太可能成為「贏者通吃」的市場。在腫瘤領域你很少看到那樣的情況。一般來說，腫瘤科醫師會抗拒依賴單一治療。因此我認為這不是非此即彼的計算。族群不同。也有各種可以採用的聯合治療策略。

And I think at the end of the day, this will become about sequencing and matching the right drug with the biology. We believe a selective G12D inhibitor be used first in G12D patients and then a non-selective later. But there again, it's not either/or. And what we do know is there's only two companies right now in Phase 3 studies with the first targeted G12D treatment in pancreatic cancer.

而且我認為到最後，關鍵會在於治療序列，以及把合適的藥物與生物學特徵做配對。我們相信在 G12D 病人中，選擇性 G12D 抑制劑會先用，之後再使用非選擇性的。但同樣地，這也不是非此即彼。我們所知道的是，目前只有兩家公司在胰臟癌的第一個標靶 G12D 治療上進入第三期研究。

And so whether you're first or early, this, for Incyte can be a real needle mover. And I think when you look at the data that we'll share at ESMO, you'll be reassured about the activity of this compound in terms of response rates as well as durability of response.

因此不論你是第一或是早期進入者，對 Incyte 來說這都可能是實質的成長推動力。我想當你看到我們將在 ESMO 分享的數據時，你會對這個化合物的活性更有信心，無論是反應率或反應持久性。

Jay Olson, Oppenheimer.

Jay Olson，Oppenheimer。

Congrats on all the progress, including closing the Vega deal. Based on everything you've learned, including feedback from KOLs at ISTH, can you comment on the potential for latarcibart to expand beyond VWD? And eventually, do you think latarcibart can be the next Hemlibra?

恭喜你們在各方面的進展，包括完成 Vega 交易。根據你們所學到的一切，包括在 ISTH 從 KOL 那裡得到的回饋，你們能否評論 latarcibart 在 VWD 之外擴展適應症的潛力？以及最終你們是否認為 latarcibart 可能成為下一個 Hemlibra？

Jay, thank you for the question. I'm going to turn it over to Dave Gardner and let him make a few comments.

Jay，謝謝你的提問。我把問題交給 Dave Gardner，請他做一些評論。

Yeah. Thanks, Jay. Yes, we did get very favorable feedback both from KOLs and importantly, from the patient advocacy channel as well A lot of the discussion was around the impressive clinical profile thus far from latarcibart. But a secondary discussion did emerge around the treatment of bleeds and the urgency to use better prophylaxis to prevent bleeds in a broader set of patients.

好的。謝謝你，Jay。是的，我們確實從 KOL 那裡、以及很重要地，從病友倡議管道也收到了非常正面的回饋。許多討論都圍繞在 latarcibart 迄今為止令人印象深刻的臨床特徵。但也出現了第二個討論方向，關於出血的治療，以及迫切需要使用更好的預防性治療，以在更廣泛的病人族群中預防出血。

So coming out of ISTH, absolutely, we are emboldened by the feedback that if we deliver on the target product profile, there is potential to deliver a transformative Hemlibra like opportunity to these patients.

因此從 ISTH 回來後，我們確實因這些回饋而更有信心：如果我們能交付目標產品特徵（TPP），就有機會為這些病人帶來類似 Hemlibra 的變革性機會。

And Jay, if you think about it, there is a hemophilia A like population in Von Willebrand's. And that is a sizable pool of patients who are severe, frequent bleeders. And if '039 comes out of Phase 3, like David said, with a substantial reduction in the annual bleed rate and a good benefit risk profile, adoption in that group, which could be almost 10,000 people would turn this into one of the largest products Incyte would have. The most important thing for us to do right now is execute this Phase 3 program, maintain the quality of the data, and then, of course, get it approved. But all of the substrate is there for this to be a large product.

而且 Jay，如果你想一想，在馮·維勒布蘭德氏病（Von Willebrand's）中其實存在一個類似血友病 A 的族群。那是一個相當可觀的病人池，屬於重度、頻繁出血者。如果如 David 所說，'039 在第三期結果顯示年出血率大幅下降，且具備良好的效益風險概況，那麼在這個族群中的採用（可能接近 10,000 人）將使其成為 Incyte 最大的產品之一。我們現在最重要的是把這個第三期計畫執行好、維持數據品質，然後當然是取得核准。但所有的基礎條件都已具備，使其有機會成為一個大型產品。

Thanks for the question.

謝謝你的提問。

Derek Archila, Wells Fargo.

Derek Archila，Wells Fargo。

So given Niktimvo's IPF data, Phase 2 data is going to come from Syndax later this year, you guys have an opt-in. So just wondering if you could walk us through kind of the decision framework what sort of data thresholds may trigger an opt in how you kind of communicate that decision and just remind us of the split on the development costs that you decide to proceed.

所以考量到 Niktimvo 的 IPF 數據，今年稍晚 Syndax 會公布第二期數據，而你們有一個選擇加入（opt-in）的權利。想請你們帶我們走一遍決策框架：什麼樣的數據門檻可能觸發你們選擇加入、你們會如何溝通這個決定，以及也請提醒我們若決定推進，研發成本分攤比例是如何？

Great. Thanks for the question. Pablo?

好的。謝謝你的提問。Pablo？

Yes, Derek. thank you for the question. The disclosure of the data, since they're conducting the study, would be done by Syndax. It would not be done by us. Obviously, they'll show the data with us. We'll discuss the results, and depending how clear they are, it will take a little bit longer or not to make the decision to pursue the indication together with Syndax.

是的，Derek，謝謝你的提問。由於研究是他們在進行，數據的揭露會由 Syndax 來做。不會由我們來公布。當然，他們會先與我們分享數據。我們會討論結果，而依據結果的清晰程度，做出是否與 Syndax 一起推進該適應症的決定，可能需要較長或較短的時間。

When it comes to the existing agreement, it's the same type of agreement we have for other indications, both sharing the development costs and sharing economics. So there's no difference. And when it comes to the opt-in, I just want to make clear that if we decide to opt in, there's nothing to prevent us from doing so. So we really look forward to hearing the data from our colleagues at Syndax, but they will be the ones releasing those results.

至於現有協議，它與我們在其他適應症上的協議類型相同：共同分攤研發成本並共享經濟利益。所以沒有差別。而關於 opt-in，我只想澄清，如果我們決定選擇加入，沒有任何事情會阻止我們這麼做。因此我們非常期待聽到 Syndax 同事公布的數據，但發布結果的人會是他們。

Andy Chen, Wolfe Research.

Andy Chen，Wolfe Research。

This is Jason taking up for Andy. And I just wanted to ask how well is the Jakafi XR conversion tracking along your internal metrics so far? And do you know when payer reimbursement might kick in? And which specific earnings will this specifically impact the most?

我是 Jason 代替 Andy 提問。我想問 Jakafi XR 的轉換進度到目前為止是否符合你們內部指標？以及你們知道付款方的給付何時會開始生效嗎？另外，接下來哪一個具體的財報期會受到最大影響？

What was the second part of the question?

問題的第二部分是什麼？

And when payer reimbursement might kick in and which of the earnings coming up will this impact the most?

以及付款方的給付何時會開始生效，以及接下來哪一個財報期會受到最大影響？

Great. Go ahead, Pablo. I mean, Mohamed, why don't you go ahead and comment on that?

好的。Pablo，你先請。我是說，Mohamed，你不如來評論一下？

Yeah. Thanks, Bill. And Jason, thanks for the question. Look, like we mentioned earlier this year, we're focused on accelerating XR formulary access because that will serve as the basis for demand growth. And we're well on track to achieve that goal of 50% to 70% formulary coverage by the end of the year.

好的。謝謝你，Bill。Jason，謝謝你的提問。你看，正如我們今年稍早提到的，我們專注於加速 XR 的處方集（formulary）准入，因為那將成為需求成長的基礎。而我們也正按計畫在年底前達成 50% 到 70% 的處方集覆蓋率目標。

So to answer your question specifically, when will pay reimbursement kick in, it has kicked in. And like Bill mentioned in the prepared remarks, several major payers have already moved and put XR on formulary. We've already seen demand start to pick up. And if by the end of the year, let's just say, December, we exit the year with XR maybe representing somewhere between 3% to 5% of our demand. That will put us somewhere in that $40 million to $50 million range that Bill mentioned in the prepared remarks, and that puts us well on our way to that 10% to 30% conversion before Jakafi LOE.

所以具體回答你關於給付何時生效的問題：已經生效了。而且如 Bill 在事先準備的發言中提到的，幾家主要付款方已經採取行動，把 XR 納入處方集。我們也已經看到需求開始回升。如果到年底，假設 12 月我們在年底時 XR 可能占我們需求的約 3% 到 5%。那會讓我們落在 Bill 在事先準備的發言中提到的 4,000 萬到 5,000 萬美元區間，也讓我們在 Jakafi 專利到期（LOE）前，朝 10% 到 30% 的轉換目標邁進。

So we're very pleased with the access so far. The market access team has done a really nice job of getting us and putting us in a position for demand generation to accelerate later in 2027.

因此我們對目前的准入進展非常滿意。市場准入團隊做得非常出色，讓我們處於一個有利位置，使需求生成在 2027 年稍後加速。

Matt Phipps, William Blair.

Matt Phipps，William Blair。

Nice execution in the quarter. Pablo, you mentioned the totality of the data did not support continue to develop '058 for the V617F indication. Over the past year, it seems like the issue has really been around the bioavailability of this drug and being able to achieve target coverage. So were there other factors as you change the formulation of things that move -- that contributed to this totality of the data. And can you just write us on the timeline for moving that backup program into the clinics and how you're thinking maybe about the internal program versus the Prelude option?

本季執行得不錯。Pablo，你提到整體數據並不支持繼續為 V617F 適應症開發 '058。過去一年看起來問題主要在於這個藥的生體可用率，以及是否能達到目標覆蓋。所以除了你們更改劑型之外，是否還有其他因素——也就是促成你所說「整體數據」判斷的因素？另外，你能否更新一下把那個備援計畫推進到臨床的時間表，以及你們如何看待內部計畫相對於 Prelude 選項？

Certainly. Thank you for the question. I think you've captured the keep point there. It was not just about availability. It was not just about exposure. We think the new formulation showed promise, and we were continuing to escalate.

當然。謝謝你的提問。我認為你抓到那裡的關鍵點了。這不只是關於可得性。也不只是關於暴露量。我們認為新的配方顯示出潛力，因此我們持續推進並逐步加碼。

When we started to look at the emerging data and what we look at, as you can imagine, is obviously the PK that you just pointed out to as well as the safety and efficacy that is emerging for a particular program. And we look at that in the context of other programs that we have in-house and that we have been advancing preclinically over the last couple of years. And when we put all that together, it just made no sense to continue to develop '058.

當我們開始檢視逐步浮現的數據時，如你所想像，我們看的當然包括你剛指出的 PK（藥物動力學），以及某個專案正在顯現的安全性與療效。我們也會把這些放在我們內部其他專案的脈絡下來看，這些專案在過去幾年也一直在做臨床前推進。把所有因素綜合起來後，繼續開發「058」就完全沒有意義了。

The next-generation programs have moved along very, very well. We're really excited about what the data looks like preclinically. We will provide an update for clinical data later this year, just so you have clarity on what the differences are between this program, this new program and '058. And we're looking to basically file the IND in the relatively near future. I won't give you a precise point in time right now, and we'll provide an update later this year when we present the data, but it's reasonably close to an IND filing.

下一代專案的進展非常、非常順利。我們對臨床前數據的表現感到非常興奮。我們會在今年稍晚提供臨床數據更新，讓你清楚了解這個專案、這個新專案與「058」之間的差異。而我們也希望在相對不久的將來提交 IND。我現在不會給出精確的時間點；我們會在今年稍晚發表數據時再更新，但距離提交 IND 已經相當近了。

On the Prelude agreement, we -- obviously, those programs are managed by Prelude terms of updates, they can provide them. The lead is in the clinic, and there are other programs that we discussed with them at the advancing to different stages of preclinical development. We will sit down with them and discuss the current data that they have. But in terms of providing further updates than that, that should be done by Prelude their programs at this point until we opt in.

關於 Prelude 的協議——很明顯，這些專案是由 Prelude 管理的，就更新而言，他們可以對外提供。領先專案已在臨床中，另外還有一些我們與他們討論過、正在推進到不同臨床前開發階段的專案。我們會與他們坐下來討論他們目前掌握的數據。但就提供更進一步的更新而言，在我們選擇 opt in 之前，這些專案的更新此時應由 Prelude 來對外說明。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO 資本市場。

I want to touch back on some of the data at ESMO, specifically on '734. As you prepare to present the PDAC and CRC data later this year, what benchmark should we use to judge success? And how much -- how would you frame your conviction in this asset versus kind of the competitive profile that we had talked about earlier on this call?

我想回到 ESMO 上的一些數據，特別是「734」。當你們準備在今年稍晚公布 PDAC 與 CRC 的數據時，我們應該用什麼基準來判斷成功？另外，相較於我們在本次電話會議較早時談到的競爭態勢，你會如何界定你們對這項資產的信心程度？

Thanks for the question, Evan. Pablo?

謝謝你的提問，Evan。Pablo？

Certainly. So thank you for the question, Evan. So when we -- the way I think about it is as follows. So the first thing, we initiated a Phase 3 trial in pancreatic cancer in combination with chemotherapy, as you know, with '734, and we've shown very little data other than ASCO GI last January. So we thought it was very important to have an expanded cohort of patients, as I mentioned, about 50 patients, about half and half with each type of chemotherapy with some maturity in order to derisk this program and generate more conviction around the first-line indication.

當然。謝謝你的提問，Evan。我對此的思考方式如下。首先，如你所知，我們已在胰臟癌啟動一項與化療合併使用「734」的第三期試驗，而我們目前除了去年一月 ASCO GI 之外，幾乎沒有展示太多數據。因此我們認為擴大病人隊列非常重要；如我提到的，大約 50 位病人、兩種化療方案各約一半，並且要有一定成熟度，才能降低這個專案風險，並對第一線適應症建立更強的信心。

When you look at benchmarks, there's two sets of benchmarks here. One is existing chemotherapy, and that's pretty clear. There's a number of publications with response rate to 30%, 40%, 45%. And then there are our competitors, which have presented some data as well in combination with chemotherapy. As we put the data at ESMO, we'll discuss it in more detail, but we think potentially we have a best-in-class agent here in combination with chemotherapy front-line pancreatic cancer. We'll discuss those results and then hopefully will be the level -- you'll share our level of conviction around that program.

談到基準，這裡有兩組基準。一組是既有化療，這相當明確。有多篇文獻顯示反應率約為 30%、40%、45%。另一組是我們的競爭對手，他們也已在與化療合併方面公布了一些數據。就我們在 ESMO 的數據而言，我們會更詳細討論，但我們認為在第一線胰臟癌與化療合併使用時，我們可能擁有同類最佳（best-in-class）的藥物。我們會討論這些結果，希望你也能認同我們對該專案的信心程度。

When it comes to colorectal cancer, obviously, that's a smaller data set, but we'll have data in combination with Erbitux. We also think potentially starts to show signs of being a best-in-class agent to combine with an EGFR inhibitor in patients with colorectal cancer, which we think it might be an underappreciated opportunity for G12D inhibitor that we intend to pursue.

至於大腸直腸癌，顯然數據集較小，但我們會有與 Erbitux 合併的數據。我們也認為，這可能開始顯示出作為同類最佳藥物的跡象，可與 EGFR 抑制劑在大腸直腸癌病人中合併使用；我們認為這可能是 G12D 抑制劑一個被低估的機會，而我們打算加以推進。

Michael Schmidt, Guggenheim.

Michael Schmidt，Guggenheim。

I had one on the PD-1 and TGF beta asset, '890. Pablo, I guess, what is your level of conviction that this could succeed in frontline colorectal cancer? How is that positioned longer term in the CRC space relative to other emerging therapies, including amivantamab or ivonescimab Phase 3? And then how do you think about other opportunities for those agents longer term?

我有一題關於 PD-1 與 TGF beta 資產「890」。Pablo，我想問，你對它在大腸直腸癌第一線治療中成功的信心程度如何？長期來看，在 CRC 領域相較於其他新興療法（包括 amivantamab 或 ivonescimab 的第三期試驗），它的定位是什麼？另外，你如何看待這些藥物長期的其他機會？

Thank you for the question, Michael. Okay. Let's start with frontline colorectal cancer. What we know today is that TGF-beta receptor 2 by PD-1 antibody generated what I would describe as the best single-agent activity have been reported for a PD-1 therapy in patients with MSS colorectal, particularly in patients with liver metastasis. That led to an acceleration of that program.

謝謝你的提問，Michael。好。我們先從大腸直腸癌第一線治療談起。我們目前所知道的是：TGF-beta 受體 2 × PD-1 抗體在我看來，已產生了目前在 MSS 大腸直腸癌病人中所報告、PD-1 治療作為單藥的最佳活性，特別是在肝轉移病人。這促使該專案加速推進。

We generated in combination with (inaudible) that first showed it was tolerable and they show increasing increasingly a level of responses and durability that convinces that was the right path forward. So what we're going to show at ESMO in a pretty large data set with a fair amount of follow-up that we believe supports the frontline strategy with all (inaudible).

我們在與（聽不清）合併的研究中產生了數據，首先顯示其可耐受，並且顯示出逐步提升的反應率與持久性，讓我們相信這是正確的前進方向。因此我們將在 ESMO 展示一個相當大的數據集，並有相當程度的追蹤期；我們相信這些結果支持以（聽不清）作為第一線策略。(聽不清)。

We're fully aware of the competitive landscape. I think the difference here, and both approaches my work, Michael. But I think the difference is pembrolizumab is a very important drug in patients with colorectal cancer. And when you give a PD-1 by VEGF, you cannot give full dose path. By giving the TGF-beta receptor 2 by PD-1, we can give with full dose bevacizumab, which we believe could potentially be a differentiating feature.

我們完全了解競爭態勢。我認為差異在於——而且兩種方法都可能有效，Michael。但我認為差異是：pembrolizumab 在大腸直腸癌病人中是一個非常重要的藥物。當你使用 PD-1 與 VEGF 的組合時，你無法給到全劑量的（聽不清）。透過使用 TGF-beta 受體 2 × PD-1，我們可以合併全劑量 bevacizumab，我們相信這可能是一個具差異化的特點。

Data over time will decide which one of those approaches is better, and both might be successful. So that's point number one. The second is we've generated data also in combination with bevacizumab alone. Some of the data might be presented at the meeting as well, and we believe also continues to show the potential of our TGF-beta receptor 2 by PD-1 in colorectal cancer more broadly.

隨著時間推進，數據會決定哪一種方法更好，而兩者也都可能成功。這是第一點。第二點是：我們也產生了與單用 bevacizumab 合併的數據。其中一些數據也可能會在會議上展示；我們相信這也持續顯示出我們的 TGF-beta 受體 2 × PD-1 在更廣泛的大腸直腸癌領域的潛力。

When it comes to the tumor types, as you know, we've done some work in other tumor types. I'm not sure we're going to have time for an update on that at ESMO. We want to focus at ESMO on the three things that I discussed in my prepared remarks. G12D in pancreatic and colorectal TGF-beta by PD-1 colorectal, and '667 in patients with ovarian cancer now in combination with bevacizumab, which we also think it's an important update derisking the maintenance study that we're conducting in that program.

至於腫瘤類型，如你所知，我們也在其他腫瘤類型做了一些工作。我不確定我們是否會有時間在 ESMO 更新那部分。我們希望在 ESMO 聚焦在我在事先準備的發言中提到的三件事：胰臟癌與大腸直腸癌的 G12D、以 TGF-beta × PD-1 治療大腸直腸癌，以及「667」在卵巢癌病人中目前與 bevacizumab 合併的進展；我們也認為這是一個重要更新，可降低我們在該專案所進行的維持治療研究風險。

Jessica Fye, JPMorgan.

Jessica Fye，摩根大通。

Just wanted to confirm what the right way to think about Opzelura gross to nets is going forward. And also, can you just remind me of your regulatory plans for povo in vitiligo?

我只是想確認一下，未來應該如何正確看待 Opzelura 的毛利到淨額（gross-to-net）。另外，你能否提醒我你們在白斑症（vitiligo）方面對 povo 的法規／監管規劃？

Great. Jess, I'll take the first part of the question, Mohamed or Suky can add. In simple terms, we were working with the gross to net in the low 60s. And with the settlement, now we're in the high 50s. And as I had mentioned at the start of the call, it just simply proves the gross-to-net profile and average selling price for Opzelura.

很好。Jess，我先回答問題的第一部分，Mohamed 或 Suky 可以補充。簡單來說，我們原本的毛到淨（gross-to-net）在 60% 出頭。而在和解之後，現在落在 50% 後段。正如我在電話會議一開始提到的，這只是單純地驗證了 Opzelura 的毛到淨結構與平均售價。

We made a strategic decision at the beginning of the year to expand access, and there was an investment associated with that. And I can tell you, here we are seven months later, and I think it was the right decision because when you look at the fundamentals of this business, which is basically volume growth, coupled with coverage, we're in a really good spot. Our job right now is to just manage this selling price as we get into '27 and '28.

我們在年初做出一項策略性決策來擴大可近性，而這也伴隨相關投資。我可以告訴你，七個月後的現在，我認為那是正確的決定，因為當你看這項業務的基本面——本質上是量的成長，加上給付覆蓋——我們處在非常好的位置。我們目前的工作就是在邁向 '27 與 '28 時，管理好這個售價。

I think that pretty much covers it. And I think I can turn it over to Pablo or Stephen to talk about the vitiligo regulatory plan.

我想這大致涵蓋了。我想我可以把時間交給 Pablo 或 Stephen 來談白斑症（vitiligo）的法規計畫。

Thank you for the question, Jess. The plan in vitiligo, after discussions we have with FDA over the past year or so is to submit right after the approval in with two years of safety data, safety follow-up in the vitiligo patients. So basically, as soon as the team is printing the filing as soon as we get the HS, and we sort of clicked a two-year follow-up, we will submit that. So it's going to go in early next year.

謝謝你的提問，Jess。關於白斑症的計畫，在過去一年左右與 FDA 討論後，我們的做法是在核准後、取得兩年的安全性資料（白斑症患者的安全性追蹤）後立即遞交。所以基本上，一旦團隊在我們拿到 HS 後就開始準備送件文件，並且我們完成兩年的追蹤，我們就會遞交。因此會在明年年初送件。

Salveen Richter, Goldman Sachs.

Salveen Richter，高盛。

Could you speak to your target profile for the mCALR program '989 as we look to first line data by year-end in both the mono and combo cohorts versus what you've established with Jakafi and the traditional endpoints of spleen and symptoms? And maybe put this in the context of the composite endpoint that you're trying to create as well.

能否談談你們對 mCALR 計畫 '989 的目標產品特性（target profile），因為我們預期在年底前會看到單藥與合併治療兩個隊列的一線數據；相較於 Jakafi 以及傳統的脾臟與症狀等終點，你們希望達到什麼？也請把這放在你們試圖建立的複合終點（composite endpoint）的脈絡下說明。

Great. Thanks for the question. Pablo?

很好。謝謝你的問題。Pablo？

Thank you, Salveen. So as I mentioned, and I won't repeat myself earlier in the call, there's two regulatory paths here. One traditional endpoints, as you allude with SVR35 and TSS50 and the conversations we're having with the FDA second-line MF. depending on the success of those conversations, some of those lessons may be applied to first-line MF or not.

謝謝你，Salveen。如我提到的，我就不重複前面電話會議的內容了，這裡有兩條法規路徑。一條是傳統終點，如你提到的 SVR35 與 TSS50，以及我們與 FDA 就二線 MF 所進行的討論。視那些討論的結果而定，其中一些經驗可能會、也可能不會，應用到一線 MF。

Our conviction here remains because of the data we presented in a small subset of tuck-in eligible patients, which is basically a JAK naive population, which we presented at EHA, and we will update later this year. We show pretty solid numbers in terms of SVR35 and TSS50, stronger in type 1 patients than non-type 1. But certainly, when you think about -- if you remember the EHA data, there were very few non-type 1 patients and have received a higher dose. And we do know those patients do need a higher dose.

我們在這裡的信心仍然來自我們在一小部分符合加用（tuck-in）條件的患者中所呈現的數據——基本上是 JAK 未治療（JAK naive）族群——我們在 EHA 上報告過，並會在今年稍晚更新。就 SVR35 與 TSS50 而言，我們顯示出相當扎實的數字；在 type 1 患者中比非 type 1 更強。但當然，若你回想 EHA 的數據，非 type 1 患者非常少，而且接受較高劑量的也不多。而我們確實知道那些患者需要更高的劑量。

So when you put all that together, our conversation with the FDA will complete the second-line MF conversations. Depending on that and whether we are able to advance a different endpoint or not, we will decide the regular path for first-line MF. As of today, our plan continues to be in first line MF to develop '989 both as a single agent and in combination with Jakafi in both in type 1 and non-type 1 patients. That's still the plan.

因此把這些都綜合起來，我們與 FDA 的對話會先完成二線 MF 的討論。視其結果以及我們是否能推進不同的終點而定，我們將決定一線 MF 的法規路徑。截至今天，我們的一線 MF 計畫仍是將 '989 同時以單藥與與 Jakafi 合併的方式開發，並涵蓋 type 1 與非 type 1 患者。計畫仍是如此。

Mitchell Kapoor, HC Wainwright.

Mitchell Kapoor，HC Wainwright。

This is Matt on for Mitchell. And I guess in the same vein, could you help the stage -- set the stage for the 2H '26 treatment-naive MF readout, what would support advancing monotherapy versus plus ruxolitinib or both? And how are you viewing the analysis of the incremental contribution of '989 in the combination are?

我是代 Mitchell 發言的 Matt。我想延續同樣的方向，能否請你們協助鋪陳一下 2026 年下半年（2H '26）治療未曾用藥（treatment-naive）的 MF 讀出：什麼情況會支持推進單藥治療、相較於加上 ruxolitinib，或兩者都推進？以及你們如何看待在合併治療中 '989 的增量貢獻（incremental contribution）的分析？

Mitchell, could you just repeat the question? Your audio broke up.

Mitchell，你可以再重複一次問題嗎？你的音訊斷斷續續。

Yeah, no problem. I was just asking if you could help set the stage for the treatment-naive MF readout. What would help support the decision to advance '989 monotherapy versus in combination?

好的，沒問題。我只是想問你們能否協助鋪陳一下治療未曾用藥的 MF 讀出。什麼會有助於支持推進 '989 單藥治療，或是合併治療的決策？

Terrific. Thank you. Look, we have the JAK in eligible cohort from EHA. So that's the first data set that we have, which is about 20 patients that showed what I would describe as strong SVR35 and TSS50 data. And as I mentioned to Salveen, maybe we needed more data at the higher doses in non-type 1 patients to sort of complete the picture.

很好。謝謝。你看，我們有來自 EHA 的 JAK 不適用（JAK ineligible）隊列。那是我們第一組數據，大約 20 位患者，顯示出我會形容為強勁的 SVR35 與 TSS50 數據。而且如我對 Salveen 提到的，也許我們需要在非 type 1 患者中取得更多高劑量的數據，才能把整體圖像補齊。

At later this year, we'll have between 50 and 60 patients worth of data with long follow-up, both in combination with Jakafi and as a single agent, that's a randomized -- small, randomized cohort. And I think all that data put together is what's going to determine which path we go forward. Based on the emerging data that we have, our plan today is develop '989 in frontline, both single agent and in combination and both in type 1 and non-type 1 patients. But obviously, the data that we're generating as we speak and that we will provide an update on later this year, we'll make the final determination there.

在今年稍晚，我們將會有約 50 到 60 位患者、且有較長追蹤期的數據，包含與 Jakafi 合併以及單藥治療；那是一個隨機分派——小型的隨機隊列。我認為把所有這些數據綜合起來，將決定我們往哪條路前進。基於目前浮現的數據，我們今天的計畫是在前線（frontline）開發 '989：同時做單藥與合併治療，並涵蓋 type 1 與非 type 1 患者。但顯然，我們正在產出的數據，以及我們今年稍晚將提供的更新，會讓我們在那時做出最終決定。

Thank you. That does conclude our question-and-answer session. Ladies and gentlemen, that does conclude today's teleconference and webcast. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.

謝謝。問答環節到此結束。各位女士、先生，今天的電話會議與網路直播到此結束。您現在可以掛斷電話，祝您有美好的一天。感謝各位今天的參與。