Jazz Pharmaceuticals PLC (JAZZ) 2024 Q3 法說會逐字稿

Ladies and gentlemen, thank you for standing by. My name is Abby, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Jazz Pharmaceuticals third-quarter 2024 earnings call. (Operator Instructions) And I would now like to turn the conference over to Andrea Flynn, Vice President and Head of Investor Relations. You may begin.

女士們先生們，謝謝你們的支持。我叫艾比，今天我將擔任你們的會議操作員。此時此刻，我歡迎大家參加 Jazz Pharmaceuticals 2024 年第三季財報電話會議。（操作員指示）我現在想將會議交給副總裁兼投資者關係主管 Andrea Flynn。你可以開始了。

Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its third-quarter 2024 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted to our website. On the call today are Bruce Cozadd, Chairman and Chief Executive Officer; Renee Gala, President and Chief Operating Officer; Rob Iannone Executive Vice President, Global Head of R&D; and Phil Johnson, Chief Financial Officer.

謝謝接線員，大家下午好。今天，爵士製藥公佈了 2024 年第三季財務業績。本網路廣播附帶的幻燈片簡報可在我們網站的投資者部分取得。投資者還可以參考我們今天早些時候發布的新聞稿，該新聞稿也發佈在我們的網站上。今天參加電話會議的是董事長兼執行長 Bruce Cozadd； Renee Gala，總裁兼營運長； Rob Iannone 執行副總裁、全球研發主管；和首席財務官菲爾·約翰遜。

On slide 2, I'd like to remind you that today's webcast includes forward-looking statements. Such as those related to our future financial and operating results, growth potential and anticipated development and commercialization milestones and goals, which involve risks and uncertainties that could cause actual events, performance and results to differ materially from those contained in the forward-looking statements.

在投影片 2 中，我想提醒您，今天的網路廣播包含前瞻性陳述。例如與我們未來的財務和營運績效、成長潛力以及預期開發和商業化里程碑和目標相關的信息，其中涉及可能導致實際事件、業績和結果與前瞻性陳述中包含的內容存在重大差異的風險和不確定性。

We encourage you to review the statements contained in today's press release in our slide deck and the risks and uncertainties described in our SEC filings, which identify certain factors that may cause the company's actual events, performance and results to differ materially from those contained in the forward-looking statements made on today's webcast. We undertake no duty or obligation to update our forward-looking statements.

我們鼓勵您查看幻燈片中今天新聞稿中包含的聲明以及我們向SEC 提交的文件中所述的風險和不確定性，這些文件確定了可能導致公司的實際事件、業績和結果與新聞稿中包含的內容存在重大差異的某些因素。我們不承擔更新前瞻性陳述的責任或義務。

As noted on slide 3, we will discuss non-GAAP financial measures on this webcast. Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and slide presentation available on the Investors section of our website.

如投影片 3 所述，我們將在此網路廣播中討論非 GAAP 財務指標。這些非 GAAP 財務指標的描述以及 GAAP 與非 GAAP 財務指標的調整包含在我們網站投資者部分提供的今天的新聞稿和幻燈片簡報中。

I'll now turn the call over to Bruce.

我現在將把電話轉給布魯斯。

Thanks, Andrea. Good afternoon, everyone, and thank you for joining us today. I'll start on slide 5. We are pleased to report on our progress in the third quarter of 2024, which was headlined by delivering strong growth across our commercial portfolio and advancing our zanidatamab development program. Recently, we achieved an important clinical milestone with positive data from our Phase 3 trial evaluating Zepzelca in first-line maintenance for extensive stage small cell lung cancer.

謝謝，安德里亞。大家下午好，感謝您今天加入我們。我將從幻燈片 5 開始。我們很高興地報告我們在 2024 年第三季度取得的進展，其中最重要的是我們的商業產品組合實現了強勁增長，並推進了我們的 zanidatamab 開發計劃。最近，我們實現了一個重要的臨床里程碑，我們的 3 期試驗評估了 Zepzelca 在廣泛期小細胞肺癌一線維持中的積極數據。

Diving into a bit more detail, I'll begin with our commercial execution for the third quarter. The durability of our neuroscience therapeutic area was underscored by both Xywav and Epidiolex posting record quarterly sales and year-over-year double-digit growth. In addition, our oncology business reported 9% revenue growth year-over-year, including a strong quarter for Zepzelca.

我將從第三季的商業執行開始更詳細地討論。Xywav 和 Epidiolex 都創下了創紀錄的季度銷售額和同比兩位數的成長，這凸顯了我們神經科學治療領域的持久性。此外，我們的腫瘤業務收入年增 9%，其中 Zepzelca 的季度表現強勁。

In our neuroscience therapeutic area, Xywav remains the oxybate of choice as the number one branded treatment for narcolepsy and the only approved therapy for idiopathic hypersomnia, or IH. In IH, physicians and patients continue to provide positive feedback on the benefits of Xywav as we build the market, and we expect this indication to drive growth for the brand.

在我們的神經科學治療領域，Xywav 仍然是首選的羥丁酸鹽，作為治療發作性睡病的第一品牌藥物，也是唯一批准的治療特發性睡眠過度症 (IH) 的藥物。在 IH 中，隨著我們建立市場，醫生和患者繼續對 Xywav 的益處提供積極的回饋，我們預計這種適應症將推動品牌的成長。

And in narcolepsy, we continue to see strong patient demand. Epidiolex growth remains strong as it nears blockbuster status. Patient demand in the US is being driven by multiple commercial initiatives, and we've made steady progress in our ongoing ex-US market expansion.

在發作性睡病方面，我們持續看到患者的強勁需求。Epidiolex 的成長依然強勁，接近重磅炸彈狀態。美國的患者需求受到多項商業計劃的推動，我們在美國以外市場的持續擴張中取得了穩步進展。

Moving to our oncology therapeutic area. Zepzelca continues to perform well, and we now have an opportunity to move from second-line treatment to first-line maintenance therapy based on the positive results of the Imforte trial. Rob will review the trial results and next steps later in the call.

轉到我們的腫瘤治療領域。Zepzelca 持續表現良好，基於 Imforte 試驗的正面結果，我們現在有機會從二線治療轉向第一線維持治療。羅布將在稍後的電話會議中審查試驗結果和後續步驟。

For Rylaze, we are seeing high utilization in the pediatric population and are continuing to roll out programs to drive adoption in the adolescent and young adult market. A recent update to Children's Oncology Group pediatric treatment protocols for ALL has impacted the timing of asparaginase administration. We expect these new protocols will have a temporary negative impact on third quarter and fourth quarter Rylaze's revenue, after which we expect demand to normalize by early next year.

對於 Rylaze，我們看到兒科人群的利用率很高，並且正在繼續推出計劃以推動青少年和年輕人市場的採用。兒童腫瘤小組最近對 ALL 兒科治療方案的更新影響了天冬酰胺酶的給藥時間。我們預計這些新協議將對 Rylaze 第三季和第四季的營收產生暫時的負面影響，之後我們預計需求將在明年初恢復正常。

Turning to our R&D and pipeline efforts. We are focused on rapidly advancing our zanidatamab program. The PDUFA date for zanidatamab in second-line biliary tract cancer or BTC, is coming up at the end of this month and we are well positioned for launch following approval. Our development program includes multiple ongoing trials in a number of HER2-positive tumors across lines of therapy. Zani is our most derisked pipeline asset and we are moving forward with a sense of urgency and purpose in order to deliver this therapy to patients with HER2-positive tumors who are in need of new and effective treatment options.

轉向我們的研發和管道工作。我們專注於快速推進我們的 zanidatamab 專案。扎尼達單抗治療二線膽道癌或 BTC 的 PDUFA 日期將於本月底到來，我們已做好準備，可以在批准後推出。我們的開發計劃包括針對多種 HER2 陽性腫瘤進行的多項跨療法試驗。Zani 是我們風險最大的管道資產，我們正帶著緊迫感和目標繼續前進，以便為需要新的有效治療方案的 HER2 陽性腫瘤患者提供這種療法。

At the start of the call, I mentioned our recent data readout on Zepzelca. We're excited that patients will potentially have access to this therapy earlier in their treatment where there is the potential to increase duration of response in a broader patient population, delaying disease progression and extending survival.

在電話會議開始時，我提到了我們最近在 Zepzelca 上讀出的數據。我們很高興患者有可能在治療早期獲得這種療法，從而有可能延長更廣泛患者群體的反應持續時間，延緩疾病進展並延長生存期。

Our commercial execution and focus on operational excellence have kept us in a strong financial position again this quarter. We continue to deliver top line growth and generate significant cash flow from operations. We remain focused on investing in the products, pipeline programs and corporate development opportunities that we believe have the highest potential to deliver sustainable growth and enhance value.

我們的商業執行力和對卓越營運的關注使我們在本季再次保持強勁的財務狀況。我們繼續實現營收成長並從營運中產生大量現金流。我們仍然專注於投資我們認為最有潛力實現永續成長和提升價值的產品、管道項目和企業發展機會。

As Phil will cover in more detail later in the call, we are affirming our total revenue and adjusted net income guidance provided on our second quarter '24 call and have updated certain other elements of our guidance. I'll now turn the call over to Renee to review our commercial performance, after which Rob will share an update on our R&D progress. Phil will provide a financial overview, and then we'll open the call to Q&A.

Phil 將在稍後的電話會議中詳細介紹，我們確認我們在 24 年第二季電話會議上提供的總收入和調整後淨利指導，並更新了指導中的某些其他要素。現在，我將把電話轉給 Renee，回顧我們的商業表現，之後 Rob 將分享我們研發進展的最新情況。菲爾將提供財務概覽，然後我們將開始問答環節。

Renee?

蕾妮？

Thanks, Bruce. I'll begin on slide 7. We're pleased with the performance of our sleep business this quarter. Total revenue, which includes Xywav and Xyrem net sales plus royalties from high sodium oxybate authorized generics or AG, was approximately $505 million.

謝謝，布魯斯。我將從幻燈片 7 開始。我們對本季睡眠業務的表現感到滿意。總收入（包括 Xywav 和 Xyrem 淨銷售額加上高羥丁酸鈉授權仿製藥或 AG 的特許權使用費）約為 5.05 億美元。

In the third quarter, Xywav net product sales grew 17% year-over-year to approximately $388 million, and we expect Xywav to continue to be the oxybate of choice in both narcolepsy and IH. We are focused on enabling as many patients as possible to benefit from low sodium Xywav and saw an increase of approximately 400 net patients exiting the third quarter compared to the second quarter.

第三季度，Xywav 產品淨銷售額年增 17%，達到約 3.88 億美元，我們預計 Xywav 將繼續成為治療發作性睡病和 IH 的首選羥丁酸鹽。我們致力於讓盡可能多的患者從低鈉 Xywav 中受益，與第二季度相比，第三季度退出的淨患者數量增加了約 400 名。

In narcolepsy, we are seeing strong demand from both new and transition patients. Further, our ongoing focus on individualized dosing and educating patients and prescribers about the benefits of reducing sodium intake continues to drive growth. And I'm pleased to report, we recorded approximately 150 net narcolepsy patient adds compared to the prior quarter.

在發作性睡病方面，我們看到新患者和過渡患者的強烈需求。此外，我們持續關注個人化劑量以及教育患者和處方醫生減少鈉攝取的好處，這將繼續推動成長。我很高興地報告，與上一季相比，我們記錄了大約 150 名發作性睡病患者淨增加。

Moving to IH. We remain excited about the growth potential of Xywav in this indication. There were approximately 3,550 active IH patients on Xywav exiting the third quarter, an increase of approximately 250 patients compared to the prior quarter, which is in line with the growth we've seen in recent quarters. Our expanded field force is continuing to focus on increasing the depth and breadth of IH prescribers, which is a primary driver of demand.

搬到IH。我們對 Xywav 在這一​​適應症方面的成長潛力仍然感到興奮。第三季約有 3,550 名使用 Xywav 的活躍 IH 患者退出，與上一季相比增加了約 250 名患者，這與我們最近幾季看到的增長情況一致。我們擴大的現場人員繼續專注於增加 IH 處方者的深度和廣度，這是需求的主要驅動力。

We are also seeing positive impact from our field nurse educator program, which supports both narcolepsy and IH indications. This program enables new Xywav patients to interact in person with trained health care professionals as they begin oxybate therapy providing education during the time when patients are titrating and optimizing their oxybate therapy and are most likely to have questions related to their treatment.

我們也看到了我們的現場護理教育計劃的積極影響，該計劃支持發作性睡病和 IH 適應症。該計劃使新的 Xywav 患者能夠在開始氧丁療法時與訓練有素的醫療保健專業人員進行面對面互動，在患者滴定和優化其氧丁療法期間以及最有可能對治療產生疑問時提供教育。

Moving to slide 8 and Epidiolex, we achieved another strong quarter with net product sales of approximately $252 million in the third quarter, representing an 18% increase compared to the same quarter in 2023. Key drivers of increased demand in the US included the positive response to data on the benefits of Epidiolex beyond seizure control, such as language and communication, cognition, executive function and emotional and social function as well as synergies from treatment with Epidiolex plus Clobazam.

轉向幻燈片 8 和 Epidiolex，我們第三季度的產品淨銷售額約為 2.52 億美元，與 2023 年同季相比增長了 18%，再次實現強勁的季度業績。美國需求增加的主要驅動因素包括對 Epidiolex 在癲癇控制之外的益處的數據的積極反應，例如語言和溝通、認知、執行功能、情感和社會功能，以及 Epidiolex 與 Clobazam 治療的協同作用。

Building on that body of evidence, which now includes data from more than 2,000 patient experiences, we presented data at the European Epilepsy Congress in September that demonstrated improvements in seizure and non-seizure outcomes in patients receiving Epidiolex in combination with Clobazam. Importantly, our improved understanding of the real-world outcomes benefits of Epidiolex not only extends to patients, but to their families and caregivers as well.

基於目前包括 2,000 多名患者經歷的數據的證據體系，我們在 9 月的歐洲癲癇大會上提供了數據，證明接受 Epidiolex 與 Clobazam 聯合治療的患者癲癇發作和非癲癇發作結果有所改善。重要的是，我們對 Epidiolex 現實世界結果的進一步了解不僅惠及患者，也惠及他們的家人和照護者。

We're also continuing to see penetration in the adult patient setting, which is supported in part by data showing that many LGS patients may reach adulthood without a specific diagnosis, and by providing health care professionals with clear diagnostic tools for adult patients. Our virtual nurse navigator program, which we launched earlier this year, provides Epidiolex patients and their families with the resource to discuss medication-related topics such as optimized dosing.

我們也繼續看到它在成人患者環境中的滲透，這在一定程度上得到了數據的支持，數據顯示許多LGS 患者可能在沒有特定診斷的情況下進入成年，並為醫療保健專業人員提供了針對成人患者的明確診斷工具。我們的虛擬護理師導航計畫於今年稍早推出，為 Epidiolex 患者及其家人提供了討論藥物相關主題（例如優化劑量）的資源。

While it's still early, we are seeing positive momentum with this program. Further opportunities for growth include focused data generation and geographic expansion beyond the more than 35 countries where Epidiolex is currently approved.

儘管現在還為時過早，但我們已經看到該計劃的積極勢頭。進一步的成長機會包括專注於數據生成以及將地理範圍擴展到目前 Epidiolex 已獲批准的超過 35 個國家。

Moving to slide 9 and our oncology business. Total oncology revenue for the quarter was approximately $285 million, representing 9% growth from the same period last year. Rylaze product sales were approximately $99 million, representing a 6% decrease from the third quarter of 2023. As Bruce noted earlier, over the summer, the Children's Oncology Group updated pediatric protocols for ALL that impact the timing of asparaginase administration.

轉到幻燈片 9 和我們的腫瘤業務。該季度腫瘤學總收入約 2.85 億美元，較去年同期成長 9%。Rylaze 產品銷售額約 9,900 萬美元，較 2023 年第三季下降 6%。正如 Bruce 早些時候指出的那樣，今年夏天，兒童腫瘤學小組更新了影響天冬酰胺酶給藥時間的 ALL 兒科方案。

Importantly, the updated protocols do not change the recommended total number of doses of asparaginase, so we do not expect an impact to overall demand for Rylaze. We anticipate the revenue impact of this timing shift to be primarily limited to the third and fourth quarter of this year and to normalize by early next year.

重要的是，更新的方案不會改變天冬酰胺酶的建議總劑量，因此我們預計不會影響 Rylaze 的整體需求。我們預計這一時間轉變對收入的影響將主要限於今年第三和第四季度，並在明年初恢復正常。

We continue to see the most opportunity for growth in the adolescent and young adult or AYA market and we are continuing to educate oncologists who treat these patients about the benefits of asparaginase therapy. This quarter, we initiated several new programs to drive AYA's adoption and continue to see opportunity to build that market over time.

我們繼續看到青少年和年輕人或 AYA 市場的最大成長機會，並且我們將繼續向治療這些患者的腫瘤學家宣傳天冬酰胺酶治療的益處。本季度，我們啟動了多項新計劃來推動 AYA 的採用，並繼續尋找隨著時間的推移建立該市場的機會。

Turning to slide 10 and Zepzelca. We delivered another strong quarter with net product sales increasing 10% year-over-year to approximately $86 million. Zepzelca remains the treatment of choice for second-line small cell lung cancer patients and health care providers continue to deliver positive feedback on the product's clinical benefit and ease of use. Last month, we were very pleased to announce positive data from the IMforte trial evaluating Zepzelca in a first-line maintenance regimen.

前往幻燈片 10 和 Zepzelca。我們的季度業績再次強勁，產品淨銷售額年增 10%，達到約 8,600 萬美元。Zepzelca 仍然是二線小細胞肺癌患者的首選治療方法，醫療保健提供者繼續對該產品的臨床益處和易用性提供積極的回饋。上個月，我們非常高興地宣布 IMforte 試驗的積極數據，該試驗評估了 Zepzelca 的一線維持方案。

Our team is preparing to submit an sNDA to include first-line maintenance therapy to the Zepzelca label. If approved, this change in practice to first-line maintenance would enable a larger number of small cell lung cancer patients to be eligible for Zepzelca treatment.

我們的團隊正在準備提交一份 sNDA，將一線維持治療納入 Zepzelca 標籤中。如果獲得批准，這一一線維持實踐的改變將使更多的小細胞肺癌患者有資格接受 Zepzelca 治療。

With that, I will turn it over to Rob for an update on our pipeline and upcoming milestones. Rob?

這樣，我將把它交給 Rob，以了解我們的管道和即將到來的里程碑的最新資訊。搶？

Thanks, Renee. Slide 12 provides an overview of the key clinical programs in our pipeline. I'll start with oncology and zanidatamab, our highest priority pipeline program. During the second quarter, FDA accepted and granted priority review for our BLA previously treated unresectable, locally advanced or metastatic HER2-positive second-line BTC setting an action date of November 29, 2024.

謝謝，蕾妮。投影片 12 概述了我們管道中的關鍵臨床項目。我將從腫瘤學和 zanidatamab 開始，這是我們最優先的管道項目。在第二季度，FDA 接受並授予了對我們先前治療的不可切除、局部晚期或轉移性 HER2 陽性二線 BTC 的 BLA 的優先審查，行動日期為 2024 年 11 月 29 日。

Enrollment for our Phase 3 first-line gastroesophageal adenocarcinoma, or GEA, trial remains on track, and we estimate top line progression-free survival or PFS data to be available in the second quarter of 2025. If the trial is positive based on PFS and supported by a trend in the interim overall survival analysis, we expect it would support registration filings.

我們的第 3 期第一線胃食道腺癌 (GEA) 試驗的招募工作仍在順利進行，我們估計最重要的無惡化存活期或 PFS 數據將於 2025 年第二季提供。如果基於 PFS 的試驗結果是正面的，並且得到中期整體生存分析趨勢的支持，我們預計它將支持註冊申請。

We have also recently initiated a Phase 2 pan-tumor trial, the study zanidatamab in a broad basket of HER2-positive solid tumors. I'll speak more to our zanidatamab development plan in just a moment. Given the opportunity to help more patients, we are very pleased with the positive results from the Phase 3 IMforte trial, which were announced last month. The trial evaluated Zepzelca in first-line maintenance therapy of extensive stage small cell lung cancer in combination with the PD-L1 inhibitor atezolizumab or Tecentriq.

我們最近也啟動了一項 2 期泛腫瘤試驗，即 zanidatamab 在 HER2 陽性實體瘤中的研究。稍後我將詳細介紹我們的 zanidatamab 開發計劃。鑑於有機會幫助更多患者，我們對上個月宣布的 3 期 IMforte 試驗的積極結果感到非常高興。該試驗評估了 Zepzelca 與 PD-L1 抑制劑 atezolizumab 或 Tecentriq 聯合治療廣泛期小細胞肺癌的一線維持治療。

Atezolizumab is the most commonly used PD-L1 agent in first-line maintenance following standard of care induction therapy with carboplatin, etoposide and immunotherapy. The combination of Zepzelca and atezolizumab demonstrated a statistically significant and clinically meaningful improvement in the primary endpoints of overall survival and progression-free survival compared to treatment for atezolizumab alone.

Atezolizumab 是繼卡鉑、依托泊苷和免疫治療的標準護理誘導治療後一線維持中最常用的 PD-L1 藥物。與單獨使用 atezolizumab 治療相比，Zepzelca 和 atezolizumab 聯合治療在總生存期和無進展生存期的主要終點方面顯示出統計學上顯著且具有臨床意義的改善。

These results demonstrated the potential of this regimen to delay disease progression and extend survival for patients with this aggressive disease. Importantly, upon approval, patients who have access to Zepzelca earlier in the treatment paradigm, where there's potential to increase duration of response in a broader patient population delaying disease progression and extending survival.

這些結果證明了該療法有可能延緩疾病進展並延長患有這種侵襲性疾病的患者的生存期。重要的是，一旦獲得批准，在治療模式早期就可以使用 Zepzelca 的患者有可能在更廣泛的患者群體中延長反應持續時間，從而延緩疾病進展並延長生存期。

We plan to submit a supplemental NDA to FDA in the first half of 2025 to expand the Zepzelca label to include first-line maintenance. We are also looking at appropriate peer-reviewed forms to present the data, which is an important step toward possible inclusion in NCCN guidelines and compendia listings.

我們計劃在 2025 年上半年向 FDA 提交補充 NDA，以將 Zepzelca 標籤擴展到包括第一線維護。我們也正在尋找適當的同儕審查表格來呈現數據，這是朝著可能納入 NCCN 指南和概要清單邁出的重要一步。

Turning to Epidiolex. In August, we announced top line data from our Phase 3 trial in Japan. While the trial did not meet the primary efficacy endpoint of change in indication associated seizure frequency during the treatment period in pediatric patients, improvements were observed in the primary and secondary endpoints.

轉向Epidiolex。八月份，我們公佈了在日本進行的第三階段試驗的主要數據。雖然該試驗未達到兒科患者治療期間適應症相關癲癇發作頻率變化的主要療效終點，但在主要和次要終點方面觀察到了改善。

We remain confident in the overall clinical profile of Epidiolex, and we are continuing to collect data in Japanese patients. We plan to engage with regulatory authorities in Japan regarding a potential new drug application. I'll also note the following discussions with FDA, we are now planning to initiate a Phase 1b trial for JZP441, our clinical stage of orexin-2 receptor agonist in narcolepsy type 1 patients in the first half of 2025.

我們對 Epidiolex 的整體臨床概況仍然充滿信心，我們正在繼續收集日本患者的數據。我們計劃與日本監管機構就潛在的新藥申請進行接觸。我還要注意以下與 FDA 的討論，我們現在計劃在 2025 年上半年啟動 JZP441 的 1b 期試驗，JZP441 是我們在 1 型嗜睡病患者中的食慾素 2 受體激動劑的臨床階段。

Turning back to zanidatamab on Slide 13. I want to touch on updated clinical data from zanidatamab in first-line GEA from an ongoing Phase 2 trial that were presented at the recent ESMO conference in September. Data from 41 patients treated with zanidatamab in combination with physician's choice chemotherapy demonstrated a confirmed objective response rate of 84% and duration of response of 18.7 months highlighting the durability of zanidatamab treatment.

回到投影片 13 上的 zanidatamab。我想談談 zanidatamab 在一線 GEA 中的最新臨床數據，這些數據來自一項正在進行的 2 期試驗，該試驗在 9 月的 ESMO 會議上公佈。來自 41 名接受扎尼達單抗合併醫師選擇化療的患者的數據顯示，客觀緩解率為 84%，緩解持續時間為 18.7 個月，凸顯了扎尼達單抗治療的持久性。

We also reported PFS of 15.2 months. And while overall survival was not yet mature after a median follow-up of 41.5 months, the Kaplan-Meier estimated 24-month overall survival was 65%, and the 30-month overall survival was 59%.

我們也報告 PFS 為 15.2 個月。雖然中位追蹤 41.5 個月後總存活率尚未成熟，但 Kaplan-Meier 估計 24 個月總存活率為 65%，30 個月總存活率為 59%。

This adds to the growing body of evidence for zanidatamab in first-line HER2-positive GEA, which also includes promising data presented at ESMO 2023 from a Phase 2 study of zanidatamab plus chemotherapy in combination with tizolizumab. The results from these separate cohorts give us confidence in both treatment arms of the Phase 3 Horizon GA01 trial we as approach the data readout expected next year.

這為 zanidatamab 在一線 HER2 陽性 GEA 中提供了越來越多的證據，其中還包括在 ESMO 2023 上公佈的 zanidatamab 加化療聯合 tizolizumab 的 2 期研究的有希望的數據。這些單獨隊列的結果使我們對 3 期 Horizo​​​​n GA01 試驗的兩個治療組充滿信心，我們接近明年預期的數據讀數。

Moving to slide 14, and an overview of our development strategy for zanidatamab. We remain excited about its potential to transform the current standard of care in multiple HER2-expressing cancers, including in cases resistant to prior HER2-targeted therapies. BTC represents our first potential approval for zanidatamab with the PDUFA action date set for November 29.

前往投影片 14，概述我們的 zanidatamab 開發策略。我們仍然對其改變多種 HER2 表達癌症（包括對先前 HER2 標靶療法抗藥性的病例）當前治療標準的潛力感到興奮。BTC 代表我們對 zanidatamab 的首次潛在批准， PDUFA 行動日期定為 11 月 29 日。

Our confirmatory Phase III trial in first-line DTC is enrolling, and we are pursuing multiple indications for HER2-positive tumors beyond BTC. As I noted, our Phase 3 trial in GEA is ongoing. We have also initiated the Phase 3 EMPOWER trial, which is designed to evaluate zanidatamab in combination with chemotherapy after progression on T-DXd where we have the opportunity to be the first HER2-targeted therapy to demonstrate efficacy and safety in breast cancer patients post T-DXd.

我們的第一線 DTC 驗證性 III 期試驗正在招募中，我們正在尋求 BTC 以外的 HER2 陽性腫瘤的多種適應症。正如我所指出的，我們在 GEA 的第 3 階段試驗正在進行中。我們也啟動了3 期EMPOWER 試驗，該試驗旨在評估T-DXd 進展後扎尼達單抗與化療的聯合治療，我們有機會成為第一個HER2 標靶療法，以證明T-DXd 後乳癌患者的有效性和安全性。

Additionally, we recently initiated a Phase 2 pan-tumor trial. Zanidatamab monotherapy has shown promising activity across a range of tumor types. And this trial is an opportunity to efficiently generate additional data across a variety of HER2 expressing solid tumors.

此外，我們最近啟動了一項二期泛腫瘤試驗。Zanidatamab 單一療法在多種腫瘤類型中顯示出有希望的活性。該試驗為有效產生各種表達 HER2 的實體腫瘤的額外數據提供了機會。

The trial is enrolling three cohorts: a pan-tumor cohort including patients with HER2-positive tumors who are HER2 treatment naive as well as two cohorts of patients who previously were treated with T-DXd. One of these cohorts is enrolling HER2-positive GEA patients and the other is enrolling HER2-positive breast cancer patients.

該試驗招募了三個隊列：一個是泛腫瘤隊列，其中包括未接受過 HER2 治療的 HER2 陽性腫瘤患者，以及兩個先前接受過 T-DXd 治療的患者群組。其中一組正在招募 HER2 陽性 GEA 患者，另一組正在招募 HER2 陽性乳癌患者。

Overall, we're excited about the prospect of delivering zanidatamab to BTC patients in the near term, and we're executing on a robust development plan based on our conviction that zanidatamab has significant potential to improve care for patients with multiple HER2-expressing tumors.

總體而言，我們對短期內向BTC 患者提供扎尼達他單抗的前景感到興奮，並且我們正在執行一項穩健的開發計劃，因為我們相信扎尼達他單抗具有改善對多種HER2 表達腫瘤患者的照護的巨大潛力。

Now I will turn the call over to Phil for a financial update. Phil?

現在我將把電話轉給菲爾，了解最新的財務狀況。菲爾？

Thanks, Rob. I'll begin on slide 16 with our top and bottom-line results. As a reminder, our full financial results are available in our press release issued earlier today and in our 10-Q, which will be filed tomorrow morning. During the third quarter of 2024, we generated more than $1.05 billion in total revenue, a 9% increase compared to the third quarter of 2023. Our strong top line performance was driven by the growth of our key products, Xywav, Epidiolex and Rylaze, which combined grew 14% year-over-year.

謝謝，羅布。我將從幻燈片 16 開始介紹我們的頂線和底線結果。謹此提醒，我們的完整財務業績可在今天早些時候發布的新聞稿和將於明天早上提交的 10-Q 報告中找到。2024 年第三季度，我們的總營收超過 10.5 億美元，比 2023 年第三季成長 9%。我們強勁的營收業績是由我們的關鍵產品 Xywav、Epidiolex 和 Rylaze 的成長所推動的，這些產品合計年增 14%。

In addition, our adjusted net income of $417 million for the quarter represents an increase of 23% compared to the third quarter of last year. We continue to generate significant cash from our business recording approximately $400 million in cash from operations in the third quarter and roughly $1 billion through the first three quarters of the year.

此外，本季調整後淨利為 4.17 億美元，較去年第三季成長 23%。我們繼續從我們的業務中產生大量現金，第三季的營運現金約為 4 億美元，今年前三個季度的營運現金約為 10 億美元。

Our strong overall financial position, including $2.6 billion in cash and cash equivalents, [means we] have significant flexibility to invest in priority commercial and R&D programs and corporate development opportunities. On our cash investment balance, I would highlight that we intend to make a substantial payment on our Term Loan B following the mid-January 2025 expiration of the 1% prepayment premium in place after our most recent repricing.

我們強大的整體財務狀況，包括 26 億美元的現金和現金等價物，[意味著我們]擁有極大的靈活性來投資優先商業和研發項目以及企業發展機會。關於我們的現金投資餘額，我想強調的是，我們打算在最近一次重新定價後 1% 的預付款溢價於 2025 年 1 月中旬到期後，對定期貸款 B 進行大量付款。

Turning to slide 17 and guidance. We are affirming full year revenue guidance of $4 billion to $4.1 billion. This represents a 6% increase in 2023 total revenue at the midpoint. We are also affirming neuroscience revenue guidance of $2.825 billion to $2.925 billion, which is a 3% increase from 2023 revenue also at the midpoint.

轉向幻燈片 17 和指導。我們確認全年收入指引為 40 億至 41 億美元。這意味著 2023 年總收入中點將成長 6%。我們也確認神經科學收入指引為 28.25 億美元至 29.25 億美元，比 2023 年收入中位數成長 3%。

Based on the temporary impact to Rylaze's revenue resulting from treatment protocol updates that Bruce and Renee spoke to earlier, we are lowering our oncology revenue guidance by $20 million to $1.08 billion to $1.13 billion. We continue to expect total revenue growth for 2024 to be driven by double-digit percentage growth of Xywav, Epidiolex and Rylaze combined.

根據 Bruce 和 Renee 先前談到的治療方案更新對 Rylaze 收入的暫時影響，我們將腫瘤學收入指導下調 2,000 萬美元，至 10.8 億美元至 11.3 億美元。我們繼續預期 2024 年總營收成長將由 Xywav、Epidiolex 和 Rylaze 組合的兩位數百分比成長所推動。

Moving on to the next slide and non-GAAP adjusted guidance. We are maintaining our prior SG&A guidance and lowering R&D guidance by $20 million to $790 million to $830 million. The reduction in expected R&D spend is primarily driven by ongoing strategic pipeline prioritization, including in response to clinical data readouts. We continue to direct investments to programs with the potential for highest impact.

轉到下一張投影片和非公認會計準則調整後的指示。我們維持先前的 SG&A 指導，並將研發指導降低 2,000 萬美元至 7.9 億美元至 8.3 億美元。預期研發支出的減少主要是由持續的策略管道優先順序所推動的，包括回應臨床數據讀數。我們繼續將投資直接投資於具有最大影響潛力的項目。

Our effective tax rate guidance remains at a range of 10% to 12%. Adjusted net income guidance remains unchanged at $1.275 billion to $1.35 billion while we are increasing our EPS range to reflect the impact on our share count of our election to settle the principal amount of our 2026 convertible notes in cash as well as a share repurchase than in conjunction with the issuance of our 2030 convertible notes. I also highlight that operating margin for the quarter was approximately 49%, bringing year-to-date operating margin to 43%, in line with our full-year guidance.

我們的有效稅率指引仍保持在 10% 至 12% 的範圍內。調整後淨利指引保持在12.75 億美元至13.5 億美元不變，同時我們正在提高每股收益範圍，以反映我們選擇以現金結算2026 年可轉換票據本金以及股票回購對我們的股份數量的影響。我還強調，本季的營業利潤率約為 49%，使年初至今的營業利潤率達到 43%，與我們的全年指引一致。

Before I turn it back over to Bruce for closing remarks, I wanted to call your attention to some additional information posted on our website. In conversations with investors and analysts since joining Jazz, some investors express interest in gaining greater visibility into the geographic breakdown of our revenue, and others ask for greater clarity on how we arrive at the shares outstanding for our GAAP and non-GAAP EPS calculations.

在我將其轉回布魯斯進行結束語之前，我想提請您注意我們網站上發布的一些附加資訊。自從加入Jazz 以來，在與投資者和分析師的對話中，一些投資者表示有興趣更清楚地了解我們收入的地理分佈情況，而其他投資者則要求更清楚地了解我們如何得出GAAP 和非GAAP 每股盈餘計算中的已發行股票。

On our website, you'll find an Excel workbook that contains historical information responsive to these requests. We hope you find this information useful in analyzing our results, and we'll continue to look for opportunities to enhance our disclosures in ways that are meaningful for investors.

在我們的網站上，您將找到一個 Excel 工作簿，其中包含回應這些請求的歷史資訊。我們希望您發現這些資訊對分析我們的結果有用，我們將繼續尋找機會，以對投資者有意義的方式加強我們的揭露。

With that, I'll turn the call back to Bruce for closing remarks.

之後，我將把電話轉回給布魯斯，讓其結束語。

I'll conclude our prepared remarks on slide 20. Our commercial execution in the quarter resulted in record quarterly revenue increasing the number of patients benefiting from Xywav with the addition of approximately 400 net patients exiting the third quarter compared to the second quarter and driving growth of Epidiolex and our oncology franchise. .

我將在投影片 20 上結束我們準備好的發言。我們在本季的商業執行創造了創紀錄的季度收入，增加了受益於Xywav 的患者數量，與第二季度相比，第三季淨增加了約400 名患者，並推動了Epidiolex 和我們的腫瘤專營權的成長。。

Our R&D engine continues to be productive, advancing our zanidatamab development program and generating data for Zepzelca that may enable us to reach more patients in critical need. And we continue to focus on operational excellence, strategic and disciplined investments in our business and retaining our strong balance sheet, which enables future growth. We're excited about the future of Jazz and believe we are well positioned to deliver growth and shareholder value.

我們的研發引擎持續保持高效，推進我們的 zanidatamab 開發計劃並為 Zepzelca 產生數據，這可能使我們能夠接觸到更多急需的患者。我們持續專注於卓越營運、對業務進行策略性和嚴格的投資，並維持強勁的資產負債表，從而實現未來的成長。我們對 Jazz 的未來感到興奮，並相信我們有能力實現成長和股東價值。

That concludes our prepared remarks. I would now like to turn the call over to the operator to open the line for Q&A.

我們準備好的演講到此結束。我現在想將電話轉給接線員以打開問答線。

(Operator Instructions)

（操作員說明）

Jessica Fye, JPMorgan.

潔西卡法耶，摩根大通。

Hey, guys. Good evening. Thanks for taking my question. I was just wondering on Xywav, can we think of the 150 net patient adds in narcolepsy as reproducible in the future? It's a big uptick from what we saw last quarter. So I'm curious how you're thinking about that. And if this might be the impact of the field nurse educator program helping with persistence in the early treatment phase? Thank you.

嘿，夥計們。晚安.感謝您提出我的問題。我只是在 Xywav 上想知道，我們是否可以認為嗜睡症中 150 名淨患者的增加在未來是可重複的？與我們上季度看到的相比，這是一個很大的上升。所以我很好奇你是怎麼想的。這是否可能是現場護理教育計劃幫助堅持早期治療階段的影響？謝謝。

Yeah. Thanks, Jess. I really appreciate the question. So definitely, we are seeing greater persistency and benefit from the field nurse educator program in addition to our wraparound services that we provide to both physicians and to patients. And that's something that we spend a lot of focus on. We think that's an important differentiator of Xywav.

是的。謝謝，傑西。我真的很感激這個問題。因此，毫無疑問，除了我們為醫生和患者提供的全方位服務外，我們還看到現場護士教育計劃具有更大的持久性和益處。這是我們花費大量精力的事情。我們認為這是 Xywav 的一個重要區別。

With respect to narcolepsy, we have seen some variability. I think what's most important to focus on is what is the source of the demand. It is coming from new patient starts. It's also coming from patient transitions from high sodium oxybate, including reversions for (inaudible) Probably the biggest factor that's driving the demand continues to be the ongoing appreciation of the benefits of low sodium by physicians and patients. Keep in mind, Xywav is the only oxybate therapy that doesn't carry a warning related to high sodium intake.

關於發作性睡病，我們看到了一些差異。我認為最重要的是關注需求的來源是什麼。它來自新患者的開始。它也來自於患者從高羥丁酸鈉的轉變，包括恢復（聽不清楚）。請記住，Xywav 是唯一一種不帶有與高鈉攝取量相關警告的羥丁療法。

So as we look holistically at the business, we're really pleased with that 150 net patient add. For the quarter, we are seeing definitely improved persistency from the field nurse educator program as I've mentioned, real appreciation, continued appreciation of the low sodium messaging and importance, in particular in this patient population that's predisposed to cardiovascular conditions. And then also, it's worth noting that this is all underpinned by what we're seeing by our field teams, which is really a strong focus on execution.

因此，當我們全面審視這項業務時，我們對淨增加 150 名患者感到非常滿意。在本季度，正如我所提到的，我們看到現場護士教育計劃的持久性明顯提高，真正欣賞、持續欣賞低鈉資訊和重要性，特別是在易患心血管疾病的患者群體中。另外，值得注意的是，這一切都是以我們的現場團隊所看到的為基礎的，這實際上是對執行的強烈關注。

Jason Gerberry, Bank of America.

傑森‧格伯里，美國銀行。

Hey, guys. Thanks for taking my question. On Zepzelca, I'm wondering -- if you can kind of help us frame the reg past. Is this submission just on the Phase III result alone? Is there any implications to this Phase III [ Lagoon ] study being confirmatory? Or does the frontline data just kind of stand on its own, and it would be its own unique, I guess, indication?

嘿，夥計們。感謝您提出我的問題。在 Zepzelca 上，我想知道 - 你是否可以幫助我們建立過去的規則。這次提交只是針對第三階段的結果嗎？這項 III 期 [Lagoon] 研究的驗證性是否有任何影響？或者前線數據只是一種獨立的數據，我猜它是它自己獨特的指示？

And thinking about the commercial opportunity. I mean, you haven't given detailed data, but presumably, you said it's clinically meaningful. So it's adding a few months of PFS. So should we just think about this as expanding the market about 7,000 patients and adding a couple of cycles of therapy. Is that the right way to be thinking about sort of the relative impact here?

並思考商業機會。我的意思是，您沒有提供詳細的數據，但想必您說這具有臨床意義。所以它增加了幾個月的 PFS。因此，我們是否應該將其視為擴大約 7,000 名患者的市場並增加幾個治療週期。這是思考相對影響的正確方法嗎？

Yes. I'm happy -- this is Rob. Thanks for the question, Jason. So the Phase 3 trial, which we said, resulted in not only statistically significant, but clinically meaningful benefit in PFS and overall survival, which was on an interim analysis. We think those data stand alone would support an expansion of the label into a frontline indication. And as we said, we're working as quickly as possible to get a submission and ultimate approval in frontline, we think this will change the standard of care in frontline therapy. And we said that submission is planned for first half next year.

是的。我很高興——這是羅布。謝謝你的提問，傑森。因此，我們所謂的 3 期試驗不僅在 PFS 和總存活率方面產生了統計學上顯著的益處，而且在臨床上有意義，這是一項中期分析。我們認為這些數據單獨將支持該標籤擴展到前線適應症。正如我們所說，我們正在盡快獲得一線的提交和最終批准，我們認為這將改變一線治療的護理標準。我們說計劃在明年上半年提交。

Part of your question was, could that also be confirmatory to our existing accelerated approval in second line. We think it can, that may depend ultimately on the timing of this submission relative to when the (inaudible) data would come in. But we certainly think these data demonstrate the benefits of Zepzelca in frontline, and that has knock-on effects for the overall activity of whether it's used in frontline or in second line.

你的部分問題是，這是否也證實了我們現有的二線加速批准。我們認為可以，這可能最終取決於此提交的時間相對於（聽不清楚）資料進入的時間。但我們當然認為這些數據證明了 Zepzelca 在一線的好處，並且無論它是用於一線還是二線，這都會對整體活動產生連鎖反應。

As we've said in the past, there's about 30,000 new small cell lung cancer patients every year, maybe 27,000 of those are extensive stage and a fraction of those are treated. So we do think that it's a larger number of patients that likely to have a longer duration of therapy as well.

正如我們過去所說，每年大約有 30,000 名新的小細胞肺癌患者，其中可能有 27,000 名處於廣泛期，其中一小部分得到了治療。因此，我們確實認為，更多的患者可能需要更長的治療時間。

Marc Goodman, Leerink Partners.

馬克古德曼，Leerink Partners。

Yes. Hi. Can you give us your latest thoughts on the orexin class, the recent data releases from competition, how you're thinking about it? And what can you share about your product 441, -- any data that you can comment on any of the commentary on the adverse events that stopped you from working on this before. Just anything more you can tell us about your product as well? Thank you.

是的。你好。您能為我們介紹一下您對食慾素類的最新想法，最近發布的比賽數據，您是如何看待它的嗎？你能分享關於你的產品的什麼441，——你可以評論任何關於之前阻止你從事這方面工作的不良事件的評論的任何數據。您還可以告訴我們有關您產品的更多資訊嗎？謝謝。

Yeah. Rob, why don't you jump in on orexins.

是的。羅布，為什麼不加入食慾素呢？

Yeah, I'm happy to. So Marc, the field is certainly advancing, especially in the NT1 space. But I would say still relatively early in a couple of respects. One is that we don't yet know what the best-in-class profile would be. Certainly, it's one that is safe and well tolerated.

是的，我很高興。所以 Marc，這個領域確實在進步，特別是在 NT1 領域。但我想說，在幾個方面還相對較早。一是我們還不知道一流的設定檔是什麼。當然，它是一種安全且耐受性良好的藥物。

And over time, we'll see what -- how these compounds compare one to the other with regard to things like potential for hepatic toxicity, potential for polyuria, visual disturbances or even insomnia based on possibly a longer half-life. We also think that this class potentially has the benefit beyond NT1, depending on the profile of the asset and NT2, IH or even other conditions of daytime sleepiness.

隨著時間的推移，我們將看到這些化合物如何在潛在的肝毒性、多尿、視覺障礙甚至失眠等方面進行比較，因為半衰期可能較長。我們還認為，此類可能具有超出 NT1 的優勢，具體取決於資產的概況和 NT2、IH 甚至其他白天嗜睡的條件。

As we mentioned, we have a Plan 1b study next year with 441 at a dose that would evaluate -- that we would evaluate in NT1 patients where we think we have potentially a therapeutic index to some of the toxicities we've seen. And that will inform not only whether 441 could go forward in any of those indications, but also potentially inform our backup programs.

正如我們所提到的，我們明年有一項計劃 1b 研究，其中 441 的劑量將進行評估——我們將在 NT1 患者中進行評估，我們認為我們對我們所看到的一些毒性有潛在的治療指數。這不僅會告知 441 是否可以在任何這些跡像中繼續前進，而且還可能告知我們的備份計劃。

Ami Fadia, Needham.

阿米法迪亞，尼達姆。

Hi, good evening. Thanks for taking my question. Just on the topic of zani. In GEA, you're conducting the Horizon 1 trial. Can you give us some sense of in the Phase 2 study, what percent of patients for PD-L1 positive versus negative and if you saw any difference in the efficacy results across the two subsets.

嗨，晚上好。感謝您提出我的問題。只是關於扎尼的話題。在 GEA 中，您正在進行 Horizo​​​​n 1 試驗。您能否為我們介紹一下 2 期研究中 PD-L1 陽性患者與陰性患者的百分比以及您是否發現兩個子集的療效結果有任何差異。

And just thinking about the (inaudible) trial. Maybe if you could just give some color on how -- I believe that Zymeworks had done some work before you guys took on zani in other cancer types. So how this basket trial and likely to be broader in kind of what areas it might be exploring? Thank you.

只是想著（聽不清楚）審判。也許你能給出一些具體的說明——我相信 Zymeworks 在你們研究其他癌症類型的紮尼之前已經做了一些工作。那麼，這項籃子試驗如何以及可能在哪些領域進行更廣泛的探索？謝謝。

Rob?

搶？

Yeah, happy to take that Bruce. So on the first one, in terms of the data we've published frontline GEA, we haven't looked at the PD-L1 status, but we also don't think in that or at least yet. We don't think that, that has any bearing on whether it's on a data map would be effective in that setting. Overall, we think the epidemiology suggests that maybe about half of patients are PD-L1 positive depending on how you define that and how you define it certainly is important because it should be defined in terms of what the cutoff is that would predict benefit from the use of a PD-1 or PD-L1 agent.

是的，很高興接受布魯斯。因此，在第一個方面，就我們發布的前線 GEA 的數據而言，我們還沒有查看 PD-L1 狀態，但我們也沒有考慮到這一點，或者至少現在還沒有考慮到這一點。我們認為，這與它在數據地圖上是否在該設定中有效沒有任何關係。總體而言，我們認為流行病學表明，大約一半的患者可能是PD-L1 陽性，這取決於您如何定義它，並且您如何定義它當然很重要，因為它應該根據預測受益的截止值來定義。

In terms of the pan-tumor study that we just started, you're absolutely right. We do have a broad experience from Phase 1 and from different cohorts we've run in patients who are overexpressing HER2. And what we find is wherever patients are overexpressing HER2, we see strong activity with zanidatamab. And based on its differentiated mechanism of action, we think that compares favorably to other agents that have been tested across a variety of tumor types.

就我們剛開始的泛腫瘤研究而言，你是完全正確的。我們確實從第一階段以及我們在過度表達 HER2 的患者中進行的不同隊列中獲得了廣泛的經驗。我們發現，只要患者過度表現 HER2，我們就會發現札尼達單抗具有強烈的活性。基於其獨特的作用機制，我們認為與已在多種腫瘤類型中進行測試的其他藥物相比具有優勢。

So what the pan-tumor study allows us to do is extend that experience, especially in a variety of rare tumors who are naive to HER2 therapies. So that could ultimately depending on the results, could ultimately support an expanded label. It also allows us to get some additional data in patients who are experienced with other HER2 agents, such as in breast cancer and gastric cancer with monotherapy that overall could support a pan-tumor indication as well.

因此，泛腫瘤研究讓我們能夠擴展這種經驗，尤其是在未接受過 HER2 療法的各種罕見腫瘤中。因此，這最終可能取決於結果，最終可能會支援擴展的標籤。它還使我們能夠獲得一些對其他 HER2 藥物有經驗的患者的額外數據，例如乳癌和胃癌的單一療法，整體上也可以支持泛腫瘤適應症。

Gregory Renza, RBC Capital Markets.

格雷戈里·倫扎（Gregory Renza），加拿大皇家銀行資本市場部。

Hi. Thank you so much for taking our questions. This is (inaudible) on for Greg. And continuing on zani, just curious with respect to the opportunity in pediatric tract cancer. Could you share with us perhaps your current thinking on how the peak assumption look like and how the ramp to that peak assumption look like in second-line pediatric tract cancer? Thank you.

你好。非常感謝您接受我們的提問。這是格雷格（聽不清楚）的。繼續扎尼，只是對小兒道癌的機會感到好奇。您能否與我們分享您目前對二線兒科癌症的峰值假設以及達到峰值假設的斜坡如何的看法？謝謝。

Yeah. So I think with respect to how to think about the ramp, it's important to remember, first, keep in mind, we don't provide product-specific guidance. But I would just remind you that BTC represents a very small patient population. And therefore, with this first indication that we're going after, the revenue expectations are quite low.

是的。因此，我認為關於如何考慮斜坡，重要的是要記住，首先，請記住，我們不提供特定於產品的指導。但我只想提醒您，BTC 代表的患者群體非常小。因此，隨著我們正在追求的第一個跡象，收入預期相當低。

When we think about BTC, this is a rare cancer, about 3,000 patients in the US in the first line and second line. However, it's also a devastating cancer with five-year survival rates less than 5% in the metastatic setting. And so for this reason, we feel very strongly in bringing the therapy forward for patients as quickly as possible, but this is not the largest opportunity set.

當我們想到 BTC 時，這是一種罕見的癌症，在美國約有 3,000 名患者處於第一線和第二線治療中。然而，它也是一種毀滅性的癌症，在轉移情況下五年存活率低於 5%。因此，出於這個原因，我們非常強烈地希望盡快為患者提供治療，但這並不是最大的機會集。

Now with that being said, we do see a much broader opportunity, one being $2 billion-plus in peak with those larger opportunities coming from GEA on target to read out in the second quarter of next year and then, of course, metastatic breast cancer and also now the pan-tumor study underway.

話雖如此，我們確實看到了一個更廣泛的機會，其中一個高峰期價值超過 20 億美元，這些更大的機會來自 GEA，目標是在明年第二季度公佈，當然還有轉移性乳腺癌現在正在進行的泛腫瘤研究。

Joseph Thome, TD Cowen.

約瑟夫·托姆，TD·考恩。

Hi, this is Payton on for Joe. Thanks for taking our questions. I guess sticking with the GEA study in zanidatamab, how important is it for the study to hit both on the doublet, RMB and the triplet RPC primary endpoint. Do you think that there will be a path forward as you see any benefit in one of these subsets? And could you maybe walk us through different scenarios for the [data readouts]? Thanks.

大家好，我是佩頓替喬代言。感謝您回答我們的問題。我認為堅持 GEA 對 zanidatamab 的研究，該研究同時達到雙重、RMB 和三重 RPC 主要終點有多重要。當您看到這些子集之一有任何好處時，您認為會有一條前進的道路嗎？您能否向我們介紹不同的場景？[數據讀數]？謝謝。

Yeah. Thanks for the question. So you're absolutely right. The trial is set up so that we have two shots on goal. There's a control arm, and then there's zani plus chemo, then there's zani, chemo with the addition of tislelizumab, which is a PD-1 inhibitor. And certainly, for approval, which we think would be supported on the basis of progression-free survival data as long as the trend in overall survival is going in the right direction.

是的。謝謝你的提問。所以你是完全正確的。試驗的安排是為了讓我們有兩次射門機會。有一個對照組，然後是紮尼加化療，然後是紮尼化療加替雷利珠單抗（一種 PD-1 抑制劑）。當然，對於批准，我們認為只要總生存期的趨勢朝著正確的方向發展，無惡化存活期數據就會支持這一點。

For approval, we need to show benefit of either arm over the control arm for the arm that includes the PD-1 agent, that has to be incrementally better than zani and chemo, so so-called contribution of components. And so we think we'll need to demonstrate that. But certainly, it gives us two shots on goal.

為了獲得批准，我們需要證明包含 PD-1 藥物的手臂相對於對照組的優勢，這必須逐漸優於扎尼和化療，即所謂的成分貢獻。所以我們認為我們需要證明這一點。但可以肯定的是，它給了我們兩次射門機會。

We have confidence based on the data that have been published in the two cohorts of first line that zani plus chemo will do very well regardless of the patient's PD-L1 status, as I mentioned before, and the addition of PD-1 gives us another opportunity because it's clear that for patients who truly are PD-L1 positive that PD-1s can incrementally improve the benefit.

根據兩個一線隊列中已發表的數據，我們有信心，無論患者的PD-L1 狀態如何，扎尼聯合化療都會效果很好，正如我之前提到的，添加PD-1 為我們提供了另一個機會機會，因為很明顯，對於真正 PD-L1 陽性的患者，PD-1 可以逐步提高療效。

Akash Tewari, Jefferies.

阿卡什·特瓦里，杰弗里斯。

Hi. This is Dennis Deja on for Akash. Thanks for taking the question. So you mentioned earlier that you have a Phase 3 zani plus chemo in HER2, HER2+ breast cancer setting. Could you give us some more details on that, maybe like the development plan, study design, timing, if you're planning any additional studies and what that patient opportunity might look like relative to GEA. And maybe just how confident you are in the HER2 resistance mechanisms [for RTEs]? Thanks.

你好。我是阿卡什的丹尼斯·德賈。感謝您提出問題。您之前提到，您對 HER2、HER2+ 乳癌進行了第 3 期扎尼加化療。您能否向我們提供更多相關細節，例如開發計劃、研究設計、時間安排、您是否計劃進行任何其他研究以及相對於 GEA 而言患者機會可能是什麼樣的。也許您對 HER2 抗藥性機制有多大信心[對於 RTE]？謝謝。

Yeah. So thanks for the question, and I'll start with the last part of it. We really feel that zanidatamab as a highly differentiated, best-in-class HER2 agent. And that's based on published data, not only on the mechanism of action and preclinical data, which you can find in Nature Communications. But the steady stream of very encouraging data across different tumor types in different combinations. And that includes several different cohorts of breast cancer patients.

是的。謝謝你的提問，我將從最後一部分開始。我們確實認為 zanidatamab 是一種高度差異化、同類最佳的 HER2 藥物。這是基於已發表的數據，而不僅僅是基於作用機制和臨床前數據，您可以在《自然通訊》中找到這些數據。但不同腫瘤類型不同組合的穩定數據非常令人鼓舞。其中包括幾個不同的乳癌患者群體。

The opportunity we see with the now ongoing Phase 3 trial is to generate data in those patients who are either intolerant to or progressed on T-DXd. As T-DXd has taken a foothold in second line and potentially moves up into frontline, -- that's the main data gap, what to treat patients with once they progressed on T-DXd.

我們在目前正在進行的 3 期試驗中看到的機會是產生那些對 T-DXd 不耐受或在 T-DXd 上出現進展的患者的數據。由於 T-DXd 已在二線站穩腳跟，並有可能進入一線，這是主要的數據差異，一旦患者在 T-DXd 上取得進展，該如何治療他們。

We think we have a growing body of data that supports the use of zanidatamab in that setting, it's differentiated, and that we see activity in patients who progressed after trastuzumab and PERJETA, patients who progress after PD-1 as well, PD-L1 as well as T-DXd. And so that's the basic concept here is that we'd be the first to generate data in those space, and it's going to be a significant unmet need, and we hope to be the first into that space.

我們認為，我們有越來越多的數據支持在這種情況下使用zanidatamab，它是有區別的，我們看到在曲妥珠單抗和PERJETA 之後出現進展的患者以及在PD-1、PD -L1 和以及T-DXd。因此，這裡的基本概念是，我們將成為第一個在這些領域產生數據的人，這將是一個重大的未滿足的需求，我們希望成為第一個進入該領域的人。

The basic design is for patients in that third line plus space, a physician would choose the backbone chemotherapy and then they would be randomized to receive a [data map] on top of that or trastuzumab. And these would be patients who had already progressed on trastuzumab where the standard of care is otherwise fairly unclear. So we think our data are very supportive of winning in that space.

基本設計是，對於第三線加空間的患者，醫生會選擇骨幹化療，然後他們將被隨機接受除此之外的[數據圖]或曲妥珠單抗。這些患者可能已經接受曲妥珠單抗治療，但治療標準卻相當不清楚。因此，我們認為我們的數據非常支持在該領域獲勝。

Annabel Samimy, Stifel.

安娜貝爾·薩米米，斯蒂菲爾。

Hey, this is (inaudible) calling in for Annabel. Thanks for taking my question. And it's related to Zepzelca. You guys showed efficacy in the first-line maintenance setting, do you now have a better idea of what the peak opportunity could be for the product? And how do you think physicians will receive the data? And will they be quick to adopt it. And then on the flip side, does that take away from the second line setting?

嘿，這是（聽不清楚）打電話給安娜貝爾。感謝您提出我的問題。它與Zepzelca有關。你們在一線維護環境中表現出了功效，現在你們是否更了解該產品的峰值機會是什麼？您認為醫生將如何接收這些數據？他們會很快採用它嗎？另一方面，這是否會影響第二行設定？

Yeah, I'm happy to jump in on that. So first of all, we're really excited about the results in the first-line trial, as Rob had mentioned earlier. We do think it will be practice changing, and we look forward to sharing the full data set in the future.

是的，我很高興能參與其中。首先，正如 Rob 之前提到的，我們對第一線試驗的結果感到非常興奮。我們確實認為這將改變實踐，我們期待將來共享完整的數據集。

Now with that being said, as we look at where we are today, it's important to note that until we have approval, we won't be actively promoting on the first-line indication, of course. I would expect we'll get use once we are adopted by NCCN guidelines, but until we get the data out there, we would not expect a ton of use in the first line. In the meantime, we're continuing to see strong use of Zepzelca in the second line even with tarlatamab on the market.

話雖如此，當我們審視我們今天的處境時，值得注意的是，在獲得批准之前，我們當然不會積極推廣一線適應症。我希望一旦我們被 NCCN 指南採用，我們就會得到使用，但在我們得到數據之前，我們不會期望在第一行中大量使用。同時，我們繼續看到 Zepzelca 在二線產品中的大量使用，即使市場上有 tarlatamab。

We have several years of being the standard of care in the second line, we have physicians getting a lot of experience with Zepzelca, and we get a lot of positive response regarding its clinical benefit, ease of use, recall, it's given in the outpatient setting and doesn't require inpatient monitoring.

多年來，我們一直是二線護理的標準，我們的醫生在 Zepzelca 方面獲得了豐富的經驗，並且我們在門診患者中使用它的臨床益處、易用性、回憶性方面得到了很多積極的回應設置，不需要住院監測。

And so we think this will bode very well for adoption in the first line once the data is available and as Rob had mentioned earlier, there's about 27,000 patients in the first line, the vast majority of those being extensive stage. So we do expect an overall increase to the revenue opportunity, given that once we get into first line, we'll be looking at a larger patient population as well as longer treatment duration. Rob, did you want to jump in as well?

因此，我們認為，一旦數據可用，這對於第一線的採用來說是一個很好的兆頭，正如 Rob 之前提到的，第一線約有 27,000 名患者，其中絕大多數處於廣泛階段。因此，我們確實預計收入機會會整體增加，因為一旦我們進入第一線，我們將關注更多的患者群體以及更長的治療持續時間。羅布，你也想跳進去嗎？

Yeah, I'd love to. I mean, as we said before, we do think these data are practice changing. We haven't shared the data themselves, but we've said not only static, but clinically meaningful differences on both PFS and overall survival, remember that overall survival was at the time of a planned interim analysis. So we think, given that we're going to move as quickly as possible, we think it's a compelling case. And physicians will find the data compelling as well, and there will be significant uptake there.

是的，我很樂意。我的意思是，正如我們之前所說，我們確實認為這些數據正在改變實踐。我們還沒有分享數據本身，但我們說過，PFS 和總生存期不僅是靜態的，而且是具有臨床意義的差異，請記住，總生存期是在計劃的中期分析時的。因此，我們認為，鑑於我們將盡快採取行動，我們認為這是一個令人信服的案例。醫生們也會發現這些數據令人信服，並且將會有大量的採用。

As I mentioned before, that does mean that it's a larger patient population that we can address, and we currently can in second line. We do expect it to be a longer duration of therapy. Remember, patients typically do not get a complete remission after their chemotherapy induction, and so they have active residual disease under the current standard and are essentially waiting to progress.

正如我之前提到的，這確實意味著我們可以解決更大的患者群體，而且我們目前可以在二線治療。我們確實預計治療時間會更長。請記住，患者在化療誘導後通常不會獲得完全緩解，因此根據當前標準，他們有活動性殘留疾病，基本上正在等待進展。

And so this has preemptively treats those patients rather than waiting for clinical progression in second line. And I think that just now the data show that, that gives them an opportunity to benefit for a longer period of time. So we do think it's more patients for a longer period of time.

因此，這可以先發制人地治療這些患者，而不是等待二線臨床進展。我認為剛才的數據表明，這給了他們一個長期受益的機會。所以我們確實認為在更長的時間內有更多的患者。

If a patient has received Zepzelca in frontline. And remember, unlike traditional induction chemotherapy, patients will get Zepzelca until progression. So we do think in that case, they wouldn't then go on to get Zepzelca again second line. But the point is that we will have preemptively use Zepzelca, which access more patients for a longer duration.

如果患者在前線接受過 Zepzelca 治療。請記住，與傳統的誘導化療不同，患者將接受 Zepzelca 直至病情進展。所以我們確實認為在這種情況下，他們不會繼續讓 Zepzelca 再次進入第二線。但關鍵是我們將搶先使用 Zepzelca，它可以在更長的時間內接觸到更多的患者。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Thanks. So my question is also on Zepzelca. And specifically, I wanted to get your thoughts on the exclusivity runway for the products. So in the orange book, you've got a patent expiration in December of '29. And then you have Orphan Exclusivity expiring in '27. With the first-line data, do you expect to get an ODE on extensive Stage (inaudible) first line? How should we think about how your exclusivity runway may or may not change with the first-line data? Thank you.

謝謝。所以我的問題也是關於 Zepzelca 的。具體來說，我想了解您對產品的獨家跑道的想法。因此，在橙皮書中，專利將於 29 年 12 月到期。然後孤兒獨佔權將於 27 年到期。有了第一行數據，您是否期望在廣泛的舞台（聽不清楚）第一行上獲得 ODE？我們應該如何考慮您的獨家跑道可能會或可能不會隨著第一線數據而改變？謝謝。

Yes. So just to jump in here in terms of thinking about the exclusivity runway, I don't think we're in a position to speculate right now on any particular updates. We're thrilled with the data that we've recently generated. As we said, we really look forward to sharing that and getting that out into the market to be able to drive further understanding of the use of Zepzelca in the first line, but I would say any further updates on IP changes over time as a result of this would be something that we would update at the time it might be relevant.

是的。因此，就跳到這裡來思考獨家跑道而言，我認為我們現在無法推測任何特定的更新。我們對最近產生的數據感到非常興奮。正如我們所說，我們真的很期待分享這一點並將其推向市場，以便能夠進一步了解 Zepzelca 在第一線的使用，但我想說隨著時間的推移，IP 變化的任何進一步更新我們會在相關時更新其中的內容。

Andrea Newkirk, Goldman Sachs.

安德里亞·紐柯克，高盛。

Thank you for taking our questions. I was just wondering here if you could provide more color on the pipeline prioritization that you mentioned? And how we should think about the makeup of the portfolio now. And then given these changes, how does that impact your appetite for potential BD transactions, whether it be in neuro versus oncology? Thanks so much.

感謝您接受我們的提問。我只是想知道您是否可以對您提到的管道優先級提供更多顏色？以及我們現在應該如何考慮投資組合的組成。然後考慮到這些變化，這將如何影響您對潛在 BD 交易的興趣，無論是神經學還是腫瘤學？非常感謝。

Yeah. Maybe I'll take the first part of that and then Phil, happy to have you jump in on the [dev] piece of it. In terms of portfolio prioritization, we are always trying to invest in those programs that we think have the most potential, particularly after we've done some derisking or proof-of-concept work, we clearly have prioritized any data map first among our existing pipeline assets given the potential broad applicability of that molecule and our excitement about that in multiple settings.

是的。也許我會先講第一部分，然後菲爾，很高興你能參與其中的[開發]部分。在投資組合優先事項方面，我們總是嘗試投資那些我們認為最有潛力的項目，特別是在我們做了一些去風險或概念驗證工作之後，我們顯然已經優先考慮了現有的任何數據圖考慮到該分子潛在的廣泛適用性以及我們對其在多種環境下的興奮，管道資產。

We do have some earlier programs we don't talk about as much on these calls, but you'll see are progressing. You can always get more information on that on our website. And then we do see some variation in R&D spend quarter to quarter depending on exactly what phase of clinical trials were in, in some cases, milestone payments if we're in partner programs. So I wouldn't read too much into that particular comment, Phil, on CorpDev.

我們確實有一些早期的計劃，我們在這些電話會議上沒有太多談論，但你會看到正在取得進展。您隨時可以在我們的網站上獲取更多相關資訊。然後，我們確實看到每個季度的研發支出存在一些變化，具體取決於臨床試驗所處的階段，在某些情況下，如果我們參與合作夥伴計劃，則需要里程碑付款。因此，菲爾，我不會過度解讀關於 CorpDev 的特定評論。

Yeah. Andrea, I'd put it in the context of our overall capital allocation. So clearly, we're seeing great growth among a number of our products that are currently on the market. So we're ensuring that we're putting the right investment behind those to maximize the benefit to patients as well as the revenue to Jazz, and then prosecuting the pipeline that we currently have in house where, as you heard on the call, zanidatamab really is sort of the key to that near-term and medium-term pipeline, and then we are looking to continue to bolster our future growth prospects through CorpDev.

是的。安德里亞，我會把它放在我們整體資本配置的背景下。很明顯，我們看到目前市場上的許多產品都出現了巨大的成長。因此，我們確保在這些項目背後進行正確的投資，以最大限度地提高患者的利益以及 Jazz 的收入，然後起訴我們目前內部的管道，正如您在電話中聽到的那樣，扎尼達瑪布確實是近期和中期管道的關鍵，然後我們希望透過CorpDev 繼續增強我們未來的成長前景。

I would say anytime you have negative readouts that probably increases the desire to do things. Obviously, we have positive readouts and things are advancing, that creates some of the internal movement that may obviate the need for some of the BD or CorpDev.

我想說的是，任何時候你得到的負面讀數都可能會增加做事的慾望。顯然，我們有積極的數據，事情正在取得進展，這產生了一些內部運動，可能會消除對某些 BD 或 CorpDev 的需求。

We definitely are actively looking at a variety of opportunities not only in oncology, but also in neuroscience as well as in select rare opportunities where we think we could deploy our capabilities, footprint to benefit patients and rapidly bring innovative therapies to market. We do have very strong cash flow, as I mentioned earlier on the call and accessibility to capital, whether that's cash on the balance sheet or through the debt markets to back those CorpDev efforts.

我們肯定正在積極尋找各種機會，不僅在腫瘤學領域，而且在神經科學領域，以及我們認為可以部署我們的能力和足跡以造福患者並迅速將創新療法推向市場的稀有機會。正如我之前在電話會議中提到的那樣，我們確實擁有非常強勁的現金流和資本獲取能力，無論是資產負債表上的現金還是透過債務市場來支持這些 CorpDev 努力。

Jeffrey Hung, Morgan Stanley.

傑弗裡洪，摩根士丹利。

Hi. This is Michael Riad on for Jeff Hung. Thank you for taking our question. Circling back to the discussion on the Orexin program. For the Phase 1b, do you have any additional color you could provide on the level of dose reduction you'd go for with 441 in Q1? And would there be like enough leeway to potentially accommodate expanding to other types of narcolepsy or IH? Thanks so much.

你好。我是邁克爾·裡亞德 (Michael Riad) 代表傑夫·洪 (Jeff Hung)。感謝您提出我們的問題。回到關於 Orexin 計劃的討論。對於 1b 期，對於第一季 441 的劑量減少水平，您是否可以提供任何其他顏色？是否有足夠的空間來適應擴展到其他類型的發作性睡病或 IH？非常感謝。

Yeah, we haven't yet disclosed the doses that we'll evaluate in the study that we described, but we will look at multiple doses because part of the goal there is to really understand relative to what we observed in healthy volunteers where we think we had a very robust effect. What's the dose that we're going to need in NT1.

是的，我們還沒有透露我們將在我們描述的研究中評估的劑量，但我們將研究多次劑量，因為目標的一部分是真正了解我們在健康志願者中觀察到的情況，我們認為我們產生了非常強勁的效果。NT1 需要多少劑量？

Obviously, we've watched other programs and we kind of see the relative dose of (inaudible) versus what they've observed in Q1. And so we need to see where we land where we think we have enough of a safety margin, and that will ultimately dictate whether we have a path forward in NT1 or in other indications where you're likely to need higher doses. So it's really the goal of the study to better characterize some of the aspects you highlight.

顯然，我們觀看了其他節目，我們看到了（聽不清楚）與他們在第一季觀察到的相對劑量。因此，我們需要看看我們認為我們有足夠的安全裕度，這最終將決定我們在 NT1 或其他可能需要更高劑量的適應症中是否有前進的道路。因此，這項研究的真正目標是更好地描述您強調的一些方面。

Joon Lee, Truist.

李俊，真理主義者。

Hey. Thanks for taking our questions. It's nice to see the growth of EBITDA like six years since the launch, how much of it is geographic expansion versus greater penetration? And for the former, what gives you confidence in approval in Japan. And for the latter, -- is there a particular segment or line of use within epilepsy that's driving growth? Thank you.

嘿。感謝您回答我們的問題。很高興看到自推出以來六年來 EBITDA 的成長，其中有多少是來自地理擴張而不是更大的滲透率？對於前者，是什麼讓你對日本的認可充滿信心。對於後者，癲癇領域是否有特定的領域或用途在推動成長？謝謝。

Yeah. Thanks for the question. I'll start out with comments on what's happening with the business currently and then ask Rob to jump in to talk a bit about the path forward in Japan. So I would say with Epidiolex, we're really pleased with the growth that we saw, 18% year-over-year. It's our highest net sales quarter to date with more than $250 million of sales. So you can see we are well on our way to having a $1 billion franchise.

是的。謝謝你的提問。我將首先對當前業務狀況進行評論，然後請 Rob 談談在日本的前進道路。因此，我想說，對於 Epidiolex，我們對所看到的同比增長 18% 感到非常滿意。這是我們迄今為止最高的淨銷售額季度，銷售額超過 2.5 億美元。所以你可以看到我們正朝著擁有 10 億美元特許經營權的目標邁進。

In terms of what's driving the growth, we continue to have Epidiolex just seen as a highly differentiated product. That starts with the data. First and foremost, we have a robust body of evidence that supports both the seizure and non-seizure benefits and that non-seizure benefit data really resonates with physicians and caregivers on those benefits such as cognition behavior, emotional, social function. So that is a very strong differentiator for Epidiolex and having an impact in the market.

就推動成長的因素而言，我們仍然將 Epidiolex 視為高度差異化的產品。這要從數據開始。首先也是最重要的，我們有大量證據支持癲癇發作和非癲癇發作益處，且非癲癇益處數據確實在認知行為、情緒、社會功能等益處方面引起了醫生和照護者的共鳴。因此，這對 Epidiolex 來說是一個非常強大的差異化因素，並對市場產生影響。

Also seeing really strong execution from the team here focused on our key drivers of growth. We've had good momentum in the adult and long-term care setting. Within the US, we've provided some new screening tools there that we talked about earlier. We have breadth and quality of our access that's continuing to improve. That's both in the US, but also some multiple positive reimbursement decisions outside the US.

我們也看到這裡的團隊非常強大的執行力，專注於我們成長的關鍵驅動力。我們在成人和長期照護領域取得了良好的發展勢頭。在美國，我們提供了一些我們之前討論過的新篩選工具。我們的訪問範圍和品質都在不斷提高。這既發生在美國，也發生在美國以外的一些積極的報銷決定。

Also, in how we're operating, we've made some structural changes to how we're organized and how our field teams collaborate, that is having a positive impact in terms of our effectiveness, and we're piloting some new programs where we're also seeing some early success in the US, we talked about the virtual nurse navigator program.

此外，在我們的運作方式方面，我們對我們的組織方式和現場團隊的協作方式進行了一些結構性改變，這對我們的效率產生了積極影響，並且我們正在試點一些新計劃，其中我們在美國也看到了一些早期的成功，我們談到了虛擬護理師導航程式。

We've rolled out new campaigns, some highly targeted consumer ads and even added a few virtual account manager positions. And the good thing about doing these pilots is, you can see what's working, you can invest more behind them and then really drive greater growth by understanding what's having an impact.

我們推出了新的廣告活動、一些針對性很強的消費者廣告，甚至還增加了一些虛擬客戶經理職位。進行這些試點的好處是，您可以看到哪些措施有效，您可以在背後投入更多資金，然後透過了解產生影響的因素來真正推動更大的成長。

Rob, would you like to cover Japan?

羅布，你想報道日本嗎？

Yeah. Just to remind folks that the -- what we reported on previously was based on an interim analysis had 13 weeks. We know the trial needs to continue to collect additional safety data at 26 and 52 weeks in order to support registration in Japan. We do think that while the efficacy at the interim didn't hit its prespecified mark, we do think the data could support registration in Japan, and we are planning to by midyear next year, have an interaction with PMDA to clarify next steps.

是的。只是提醒大家，我們之前的報告是基於 13 週的中期分析。我們知道該試驗需要在 26 週和 52 週時繼續收集額外的安全數據，以支持在日本的註冊。我們確實認為，雖然臨時的功效沒有達到預先設定的標準，但我們確實認為數據可以支持在日本的註冊，並且我們計劃在明年年中之前與 PMDA 進行互動，以明確後續步驟。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

Hi, this is (inaudible) on for Mohit. Thanks for taking our questions. I wanted to ask on the lowered oncology guidance. And if that's all due to Rylaze and the political change in the pediatric study? Or is slower than expected update in that adolescent and adult market, also a factor? Thank you.

大家好，這是 Mohit 的（聽不清楚）。感謝您回答我們的問題。我想詢問降低的腫瘤學指導。如果這一切都是由於 Rylaze 和兒科研究中的政治變化？或者青少年和成人市場的更新速度比預期慢也是一個因素？謝謝。

It's entirely due to that temporary impact we're seeing on Rylaze. That's what drove the change.

這完全是由於我們在 Rylaze 身上看到的暫時影響。這就是推動這一變化的原因。

Gary Nachman, Raymond James.

加里·納赫曼，雷蒙德·詹姆斯。

Hi. Good afternoon. Just following up on oncology. So specifically, with Rylaze, just talk about your initiatives to expand more in AYA. And has anything changed and where you see the peak potential for that opportunity? And then also, Defitelio was noticeably higher in the third quarter. So anything worth highlighting there just if that's durable going forward? Thanks.

你好。午安.只是跟進腫瘤學。具體而言，請與 Rylaze 談談您在 AYA 中進行更多擴充的舉措。有什麼改變嗎？此外，Defitelio 在第三季的表現也明顯更高。那麼，有什麼值得強調的，只要它能持久發展呢？謝謝。

Yeah. Thanks for the question. So maybe I'll just start with Defitelio. Of course, as you know, this is a product that has quarter-to-quarter variability given that historically it has given that is used to treat an ultra-rare condition. With respect to what we saw in the current quarter, we did see an increase in both the US as well as ex-US. I would say ex-US, very much related to timing and quarterly variability.

是的。謝謝你的提問。所以也許我會從 Defitelio 開始。當然，如您所知，這是一種具有季度變化的產品，因為歷史上它曾用於治療極其罕見的疾病。就我們本季看到的情況而言，我們確實看到美國和美國以外地區的成長。我想說的是美國以外的地區，與時間和季度變化密切相關。

Within the US, we saw an increase across both our adults and pediatric patients because this is weight-based dosing, you would see revenue uptick coming from an increase in adult patients, and then we've also separately seen increased use of inotuzumab. This is something that is used typically to prep patients for stem cell transplants. It could be driving greater use of Defitelio because it's also a risk factor for VOD. But it's a little too early to tell if this is going to be durable. I would for the time being, think about it as that typical variability that we'll continue to monitor.

在美國，我們看到成人和兒童患者的用藥劑量都有所增加，因為這是基於體重的劑量，您會看到成人患者的增加帶來收入的增加，然後我們也分別看到伊諾珠單抗的使用增加。這通常用於為患者進行幹細胞移植做準備。它可能會推動 Defitelio 的更多使用，因為它也是 VOD 的風險因素。但現在判斷這是否會持久還為時過早。我暫時將其視為我們將繼續監控的典型變異性。

With respect to Rylaze, we did talk about the temporary impact to Rylaze from this protocol update, which by the way, is great news for patients because ultimately, the change was driven by data that showed really meaningful improvements in survival rates by adopting this new protocol. And for this reason, we do have confidence that the protocol will be widely and rapidly adopted. And given this protocol emphasizes the same number of doses of asparaginase treatment, it also underpins the importance of asparaginase treatment as part of this overall pediatric ALL protocol.

With respect to Rylaze, we did talk about the temporary impact to Rylaze from this protocol update, which by the way, is great news for patients because ultimately, the change was driven by data that showed really meaningful improvements in survival rates by adopting this new協定.基於這個原因，我們確實有信心該協議將得到廣泛、迅速的採用。鑑於該方案強調相同劑量的天冬酰胺酶治療，它也強調了天冬酰胺酶治療作為整個兒科 ALL 方案一部分的重要性。

With respect to AYA, that build is happening probably a little more slowly than we had originally anticipated. With respect to initiatives that we have underway, we've continued to educate on the benefits of the (inaudible) focusing on the importance of that in treating the AYA population. We're also doing some piloting to see what is having an impact in moving the needle here. I won't go into all of those, but similar to what I described in our Epidiolex franchise where the field teams are continuing to work through what can have the most impact.

就 AYA 而言，該建造的速度可能比我們最初預期的要慢一些。關於我們正在進行的舉措，我們繼續宣傳（聽不清楚）的好處，並專注於其在治療 AYA 人群中的重要性。我們還在進行一些試點，看看是什麼對推動這裡的發展產生影響。我不會詳細討論所有這些，但與我在 Epidiolex 特許經營中所描述的類似，現場團隊正在繼續努力解決能夠產生最大影響的事情。

All right. It looks like that was our last question. So let me wrap by recognizing our Jazz colleagues for their efforts on behalf of patients and their families and thank our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

好的。看來這是我們最後一個問題了。最後，我要對我們的 Jazz 同事為患者及其家人所做的努力表示認可，並感謝我們的合作夥伴和股東一直以來的信任和支持。感謝大家今天加入我們。

And ladies and gentlemen, this concludes today's call, and we thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束，我們感謝你們的參與。您現在可以斷開連線。