Jazz Pharmaceuticals PLC (JAZZ) 2025 Q1 法說會逐字稿

Hello and thank you for standing by. My name is Tiffany, and I will be your conference operator today. At this time, I would like to welcome everyone to the Jazz Pharmaceuticals first-quarter 2025 webcast conference call. (Operator Instructions)

您好，感謝您的支持。我叫蒂芬妮，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Jazz Pharmaceuticals 2025 年第一季網路廣播電話會議。（操作員指示）

Thank you. I would now like to turn the call over to Executive Director of Investor Relations, Jeff Macdonald. Please go ahead.

謝謝。現在我想將電話轉給投資者關係執行董事傑夫麥克唐納。請繼續。

Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its first quarter of 2025 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website. Investors should also refer to the press release we issued earlier today that is available on our website.

謝謝接線員，大家下午好。今天，Jazz Pharmaceuticals 公佈了其 2025 年第一季的財務業績。本次網路廣播的幻燈片簡報可在我們網站的「投資者」部分找到。投資者還應參閱我們今天早些時候發布的新聞稿，該新聞稿可在我們的網站上查閱。

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 Chief Medical Officer; and Phil Johnson, Chief Financial Officer.

今天參加電話會議的有董事長兼首席執行官 Bruce Cozadd； Renee Gala，總裁兼首席營運官； Rob Iannone，執行副總裁、全球研發主管兼首席醫療官；以及首席財務官菲爾·約翰遜 (Phil Johnson)。

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, regulatory and commercial milestones and goals, which involve risks and uncertainties that could cause actual events, performance, and results to differ materially from those contained in these forward-looking statements.

在第 2 張投影片上，我想提醒您，今天的網路廣播包括前瞻性陳述，例如與我們未來財務和經營業績、成長潛力和預期發展、監管和商業里程碑和目標相關的陳述，這些陳述涉及風險和不確定性，可能導致實際事件、表現和結果與這些前瞻性陳述中的內容存在重大差異。

We encourage you to review the statements contained in today's press release in our slide deck and the risks and uncertainties described under the caption Risk Factors in our annual report on Form 10-K for the fiscal year ended December 31, 2024, and our subsequent filings with the SEC, including our quarterly report on Form 10-Q for the financial quarter ended March 31, 2025, which identified 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.

我們鼓勵您查看我們投影片中今天新聞稿中包含的聲明，以及我們截至2024年12月31日財年的10-K表年度報告中「風險因素」標題下描述的風險和不確定性，以及我們隨後向美國證券交易委員會提交的文件，包括截至2025年3月31日財季的10-Q表季度報告可能導致某些目標和今天的企業報告實際報告可能導致某些目標和今天的企業報告實際事件可能導致某些風險與今天的企業報告實際上與某些風險）與今天的企業報告實際相關。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 reconciliation of GAAPs to non-GAAP financial measures are included in today's press release and the slide presentation available on the Investors section of our website.

如投影片 3 所述，我們將在本次網路廣播中討論非 GAAP 財務指標。這些非公認會計準則 (non-GAAP) 財務指標的描述以及公認會計準則 (GAAP) 與非公認會計準則 (non-GAAP) 財務指標的對帳均包含在今天的新聞稿和我們網站「投資者」部分提供的幻燈片演示中。

I'll now send the call over to Bruce.

我現在將把電話轉給布魯斯。

Thanks, Jeff. Good afternoon, everyone. Thank you for joining us today to discuss Jazz's first-quarter 2025 results. I'll start on slide 5.

謝謝，傑夫。大家下午好。感謝您今天加入我們討論 Jazz 2025 年第一季的表現。我將從第 5 張投影片開始。

Jazz started the year with strong momentum following a productive 2024, and we're pleased with the meaningful progress we've made across the business in the first quarter of 2025. Our focus on execution and operational excellence resulted in solid commercial performance led by Epidiolex and Zywav and significant progress across our R&D pipeline.

繼 2024 年取得豐碩成果之後，Jazz 以強勁勢頭開啟了新的一年，我們對 2025 年第一季整個業務的重大進展感到滿意。我們專注於執行和卓越運營，從而取得了以 Epidiolex 和 Zywav 為首的穩健商業業績，並在我們的研發管道中取得了重大進展。

We submitted a supplemental new drug application or sNDA, to expand Zepzelca into first line maintenance in extensive stage small cell lung cancer and received a positive CHMP opinion recommending the marketing authorization for Zanidatamab and advanced HER2 positive biliary tract cancer or BTC in the European Union. In addition, the acquisition of Chimerix has further strengthened our presence in rare oncology.

我們提交了補充新藥申請或 sNDA，將 Zepzelca 擴展為廣泛期小細胞肺癌的一線維持治療，並獲得了 CHMP 的積極意見，建議在歐盟授權 Zanidatamab 和晚期 HER2 陽性膽道癌或 BTC 進行營銷。此外，收購 Chimerix 進一步加強了我們在罕見腫瘤領域的地位。

On the commercial front, we generated $898 million in total revenues across our portfolio. Our neuroscience portfolio had a strong start to the year, with Zywav growing 9% year over year, remaining the number one branded treatment for narcolepsy as measured by revenue and the only therapy approved to treat idiopathic hypersomnia or IH. We saw strong Epidiolex demand as revenues increased 10% year over year, and we remain confident in its blockbuster potential.

在商業方面，我們的投資組合總收入為 8.98 億美元。我們的神經科學產品組合今年開局強勁，其中 Zywav 年比增長 9%，以收入衡量，仍然是治療嗜睡症的第一大品牌藥物，也是唯一獲準治療特發性嗜睡症或 IH 的藥物。我們看到 Epidiolex 的需求強勁，營收年增 10%，我們對其重磅藥物潛力仍然充滿信心。

While we experience near-term headwinds with certain oncology products, our oncology portfolio is poised for growth with three potential regulatory approvals in the coming months, including Dordaviprone, Zepzelca expansion and the first line maintenance therapy in the US, and Zanidatamab advanced BTC in Europe.

雖然我們在某些​​腫瘤產品上遇到了短期阻力，但我們的腫瘤產品組合有望實現成長，未來幾個月將獲得三項潛在的監管批准，包括美國的 Dordaviprone、Zepzelca 擴展和一線維持療法，以及歐洲的 Zanidatamab 高級 BTC。

Moving to R&D, we're advancing promising opportunities in our pipeline. The HERIZON-GEA-01 Phase 3 trial, evaluating Zanidatamab in first-line gastroesophageal adenocarcinoma or GEA remains on track to read out in the second half of this year. We continue to progress other key Zanidatamab clinical trials, including the Phase 3 EmpowHER-BC-303 trial in breast cancer. We're looking forward to sharing important data on Zepzelca, Zanidatamab, and Dordaviprone at ASCO in June.

在研發方面，我們正在推進我們管道中的有前景的機會。HERIZON-GEA-01 第 3 階段試驗評估了 Zanidatamab 在第一線治療胃食道腺癌或 GEA 的療效，預計今年下半年完成。我們繼續推進其他關鍵的 Zanidatamab 臨床試驗，包括乳癌的 3 期 EmpowHER-BC-303 試驗。我們期待在 6 月的 ASCO 上分享有關 Zepzelca、Zanidatamab 和 Dordaviprone 的重要數據。

We added Dordaviprone to our pipelines through the Chimerix acquisition which closed in April, enhancing our presence in rare oncology and bringing a near-term commercial opportunity to help patients with limited treatment options. Given its patent protection into 2037 with possible extensions and the potential for expanded use in the frontline setting, we view Dordaviprone as a meaningful and durable revenue opportunity for Jazz.

我們透過 4 月完成的 Chimerix 收購將 Dordaviprone 添加到我們的產品線中，增強了我們在罕見腫瘤學領域的地位，並帶來了近期的商業機會，以幫助治療選擇有限的患者。鑑於其專利保護期將持續到 2037 年並可能延長，以及在前線環境中擴大使用的潛力，我們認為 Dordaviprone 對 Jazz 來說是一個有意義且持久的收入機會。

We are well positioned with respect to the impact of potential tariffs and have maintained financial flexibility supported by our strong balance sheet and cash flow. We remain confident in our top line revenue guidance and have updated our financial guidance to include the recent Chimerix acquisition and litigation settlement charges.

我們在應對潛在關稅的影響方面處於有利地位，並且在強勁的資產負債表和現金流的支持下保持了財務靈活性。我們對我們的營業收入指引仍然充滿信心，並已更新我們的財務指引，以包括最近的 Chimerix 收購和訴訟和解費用。

I'll now turn the call over to Renee to discuss our commercial performance, after which Rob will cover our R&D pipeline. Phil will then provide a financial overview and discuss our updated guidance, and after that, we will open the call to Q&A. Renee?

現在我將把電話轉給 Renee 來討論我們的商業表現，之後 Rob 將介紹我們的研發管道。然後，菲爾將提供財務概覽並討論我們的最新指導，之後，我們將開始問答環節。蕾妮？

Thanks, Bruce. I'll begin on slide 7 to discuss the continued progress of our commercial portfolio, starting with our sleep therapeutic area.

謝謝，布魯斯。我將從第 7 張投影片開始討論我們商業組合的持續進展，首先是我們的睡眠治療領域。

I'm pleased to report total revenue for sleep, which includes Zywav and Xyrem net product sales plus royalties from high sodium oxidate authorized generics, or AGs, was approximately $431 million in the first quarter of 2025. Zywav net product sales were approximately $345 million in the first quarter, an increase of 9% year over year.

我很高興地報告，2025 年第一季睡眠總收入約為 4.31 億美元，其中包括 Zywav 和 Xyrem 淨產品銷售額加上高氧化鈉授權仿製藥或 AG 的特許權使用費。Zywav 第一季淨產品銷售額約 3.45 億美元，較去年同期成長 9%。

As a reminder, we typically see seasonality in our sleep revenue due to reauthorizations at the beginning of each year. Despite the expected seasonality, Zywav had a robust quarter of patient adds driven by strong execution from the field teams, and we continue to be excited about the direction of our sleep portfolio.

提醒一下，由於每年年初的重新授權，我們的睡眠收入通常會呈現季節性。儘管存在預期的季節性因素，但由於現場團隊的強大執行力，Zywav 本季的患者新增量仍然強勁，我們繼續對我們的睡眠產品組合的發展方向感到興奮。

There were approximately 14,600 active Zywav patients exiting the first quarter, representing an increase of approximately 450 net patient adds compared to the fourth quarter of 2024, comprised of 125 narcolepsy patients and 325 IH patients.

第一季度，Zywav 的活躍患者約有 14,600 名，與 2024 年第四季相比淨增約 450 名，其中包括 125 名嗜睡症患者和 325 名 IH 患者。

Narcolepsy patient adds consisted predominantly of oxidate naive patients along with patients transitioning from high sodium oxybates. Our efforts to educate on the importance of reducing sodium intake and the increased risk of cardiovascular comorbidities among narcolepsy patients continue to resonate with HCPs and with patients.

嗜睡症患者主要由未接受過氧化氫​​治療的患者以及從高鈉羥基丁酸鹽過渡的患者組成。我們致力於教育嗜睡症患者減少鈉攝取的重要性以及心血管合併症風險的增加，這繼續引起醫護人員和患者的共鳴。

We see the most opportunity for patient growth from the IH market, where Zywav is the first and only FDA-approved therapy. As we continue to build this market, disease education on the benefits of using a nighttime therapy to address sleep inertia and symptoms like brain fog and excessive daytime sleepiness for IH remains important to drive prescribing.

我們認為 IH 市場具有最大的患者成長機會，其中 Zywav 是第一個也是唯一獲得 FDA 批准的治療方法。隨著我們繼續開拓這個市場，關於使用夜間療法解決睡眠慣性以及腦霧和白天過度嗜睡等 IH 症狀的好處的疾病教育對於推動處方仍然很重要。

We've launched consumer-targeted digital and media campaigns to increase disease awareness coupled with promotion and medical education to HCPs. These campaigns are performing well, contributing to the growth of the IH market, and we continue to enhance our field effectiveness to optimize our impact for patients.

我們發起了針對消費者的數位和媒體活動，以提高疾病意識，並向醫療保健人員進行宣傳和醫學教育。這些活動表現良好，促進了 IH 市場的成長，我們將繼續提高現場效率，以優化我們對患者的影響。

Turning to slide 8 in Epidiolex, Epidiolex had net product sales of approximately $218 million in the first quarter, a 10% increase year over year. Growth was primarily driven by underlying demand and to a lesser extent, a favorable US payer mix, partially offset by US inventory burn. Exiting the first quarter, inventory was lower than we would typically see at this time of the year.

翻到 Epidiolex 的第 8 張幻燈片，Epidiolex 第一季的淨產品銷售額約為 2.18 億美元，較去年同期成長 10%。成長主要受到潛在需求的推動，在較小程度上也受到美國有利的付款人組合的推動，但部分被美國庫存消耗所抵消。第一季結束時，庫存低於我們通常每年這個時候看到的水平。

Our Epidiolex commercial and medical teams have been executing well, with key drivers of demand growth in the US, including continued data generation on the benefits of Epidiolex beyond seizure control, expanded reach to adult patients and long-term care facilities, along with broad quality access and the nurse navigator program. We're pleased with the growth of Epidiolex and expected to reach blockbuster status in 2025.

我們的 Epidiolex 商業和醫療團隊表現良好，其主要需求成長驅動力來自美國，包括持續產生有關 Epidiolex 在控制癲癇發作之外的益處的數據、擴大對成年患者和長期護理機構的覆蓋範圍，以及廣泛的品質訪問和護理導航計劃。我們對 Epidiolex 的成長感到滿意，預計該藥物將在 2025 年達到重磅藥物的地位。

Moving to oncology on slide 9, Rylaze's net product sales were approximately $94 million in the first quarter of 2025, a decrease of 8% year over year. As we previously noted, Rylaze sales have been impacted by the update to Children's Oncology Group, or COG pediatric treatment protocols for acute lymphoblastic leukemia made in mid-2024.

轉到第 9 張投影片上的腫瘤學，Rylaze 的淨產品銷售額在 2025 年第一季約為 9,400 萬美元，年減 8%。正如我們之前所指出的，Rylaze 的銷售受到了 2024 年中期兒童腫瘤組或 COG 兒科急性淋巴細胞白血病治療方案更新的影響。

Based on feedback from KOLs about their expected use of asparaginase, we continue to see the impact to Rylaze as temporary, with revenue normalizing during the second quarter of 2025. We are making steady progress in the adolescent and young adult market and continue (technical difficulty) to place Zepzelca back on a growth trajectory.

根據 KOL 對天冬酰胺酶預期使用的回饋，我們仍然認為對 Rylaze 的影響是暫時的，收入將在 2025 年第二季恢復正常。我們在青少年和年輕人市場取得了穩步進展，並繼續（技術難度）讓 Zepzelca 重回成長軌道。

Moving to slide 11 in our ongoing Ziihera launch. In December of last year, FDA approved Ziihera, the first and only dual HER2-targeted bispecific antibody approved for HER2 positive second line BTC in the US. We recognize that approximately $2 million on net product sales on the first quarter of 2025.

前往我們正在進行的 Ziihera 發表會的第 11 張投影片。去年12月，FDA批准了Ziihera，這是美國第一個也是唯一獲準用於治療HER2陽性二線BTC的針對HER2的雙特異性抗體。我們認識到 2025 年第一季的淨產品銷售額約為 200 萬美元。

While (technical difficulty) has been positive, initial customers' experiences are aligned with the clinical profile in the clinical trials.

雖然（技術難度）是正面的，但初始客戶的體驗與臨床試驗中的臨床概況一致。

As a reminder, BTC is a rare disease with a limited number of patients, and we expect revenue contribution to be modest from this rare cancer. We expect this initial launch and second line HER2 positive BTC will help us (technical difficulty) HER2-targeted therapy (technical difficulty) significant benefit for patients. In addition, the BTC approval helps healthcare professionals gain meaningful experience with Ziihera prior to its potential indication in GEA.

提醒一下，BTC 是一種罕見疾病，患者數量有限，我們預計這種罕見癌症的收入貢獻不會太大。我們預計此次首次推出和二線 HER2 陽性 BTC 將幫助我們（技術難度）HER2 標靶治療（技術難度）為患者帶來顯著益處。此外，BTC 的批准有助於醫療保健專業人員在 Ziihera 可能在 GEA 中應用之前獲得有意義的使用經驗。

I will now turn it over to Rob for an update on our pipeline and upcoming milestones.

現在我將把話題交給 Rob，讓他介紹我們的管道和即將到來的里程碑的最新情況。

Thanks, Renee. I'll begin on slide 13.

謝謝，蕾妮。我將從第 13 張投影片開始。

I'm excited about our pipeline and the significant progress we have made on key programs with additional milestones expected this year. Looking first at oncology, we completed the submission of an FMDA to FDA to expand the Zepzelca label to include maintenance therapy in first line extensive stage small cell lung cancer for patients who have not progressed during induction chemotherapy.

我對我們的產品線以及我們在關鍵項目上取得的重大進展感到非常興奮，預計今年還會有更多里程碑。首先從腫瘤學角度來看，我們完成了向 FDA 提交 FMDA 的申請，以擴大 Zepzelca 的標籤，將誘導化療期間未進展的廣泛期小細胞肺癌患者的一線維持治療納入其中。

The submission is based on statistically significant and clinically meaningful progression-free survival or PFS, and overall survival or OS data from the Phase 3 and four-day trial of Zepzelca in combination with atezolizumab compared to an atezolizumab alone. The results have the potential to be practice changing and we look forward to showcasing the data in an oral presentation at ASCO on Monday, June 2.

此次提交的數據是基於 Zepzelca 與 atezolizumab 聯合用藥與單獨使用 atezolizumab 相比的 3 期 4 天試驗中具有統計學意義和臨床意義的無進展生存期或 PFS，以及總體生存期或 OS 數據。研究結果有可能改變實踐，我們期待在 6 月 2 日星期一的 ASCO 口頭報告中展示這些數據。

Presentation in a peer reviewed form also enables us to submit the data for potential inclusion in NCCN guidelines and compendia listing.

以同行評審的形式呈現也使我們能夠提交數據，以便將其納入 NCCN 指南和概要清單。

We also remain on track for top line readout of PFS data from the HERIZON-GEA-01 trial in the second half of this year. The first interim analysis of OS will also occur at this time. We are encouraged by the positive results from two independent Phase 2 trials of Zanidatamab and first line GEA that demonstrated increased median PFS, duration of response, and confirmed objective response rates. If the Phase 3 trial findings are positive, we expect the data will support registration based on potentially clinically meaningful PFS and supportive OS data.

我們也將在今年下半年繼續關注 HERIZON-GEA-01 試驗的 PFS 數據頂線讀數。此時也將進行 OS 的第一次中期分析。我們對 Zanidatamab 和一線 GEA 的兩項獨立 2 期試驗的正面結果感到鼓舞，這兩項試驗顯示中位 PFS、緩解持續時間和確認的客觀緩解率均有所增加。如果第 3 階段試驗結果是正面的，我們預計資料將基於具有潛在臨床意義的 PFS 和支持性 OS 資料支援註冊。

Three Zanidatamab presentations have been accepted at ASCO, including updated overall survival data from the Phase 2 first-line GEA trial. In addition, there will be an oral presentation on the safety and efficacy of Dordaviprone.

ASCO 已接受三份 Zanidatamab 報告，包括來自第 2 階段一線 GEA 試驗的最新總體存活數據。此外，還將進行關於 Dordaviprone 安全性和有效性的口頭報告。

Turning to neuroscience, we recently initiated our planned Phase 1b trial to evaluate the efficacy, safety, tolerability, and pharmacokinetics of JZP 441 in participants with Type 1 narcolepsy.

談到神經科學，我們最近啟動了計劃中的 1b 期試驗，以評估 JZP 441 對第 1 型嗜睡症患者的療效、安全性、耐受性和藥物動力學。

And with respect to our Epidyolex trial in Japan, we are continuing to collect long-term safety data, which was included in the trial design for 26- and 52-week analysis. We observed numeric improvements in both the primary and several secondary endpoints, and we remain on track to meet with the Japanese health authorities in mid 2025.

關於我們在日本進行的 Epidyolex 試驗，我們正在繼續收集長期安全數據，這些數據包含在 26 週和 52 週分析的試驗設計中。我們觀察到主要終點和幾個次要終點的數值都有所改善，並且我們仍有望在 2025 年中期與日本衛生當局會面。

As outlined on slide 14, Zanidatamab has proven to be a unique, differentiated, and highly effective dual targeted HER2 therapy. Zanidatamab provides opportunities across multiple HER2 positive solid tumors and represents a global opportunity for Jazz in multiple markets. Following the FDA approval of Zanidatamab in second-line BTC last year, the CHMP recently adopted a positive opinion recommending the marketing authorization of Zanidatamab for the treatment of adults with previously treated, unresectable, locally advanced or metastatic HER2 positive BTC.

如幻燈片 14 所述，Zanidatamab 已被證明是一種獨特、差異化且高效的雙標靶 HER2 療法。Zanidatamab 為多種 HER2 陽性實體瘤提供了治療機會，也為 Jazz 在多個市場帶來了全球機會。繼去年 FDA 批准 Zanidatamab 用於二線 BTC 治療後，CHMP 最近也採取了積極意見，建議授權 Zanidatamab 用於治療既往接受過治療、無法切除、局部晚期或轉移性 HER2 陽性 BTC 的成人患者。

We look forward to the European Commission's decision and for the opportunity to bring a new treatment option to patients in Europe if approved.

我們期待歐盟委員會的決定，並期待如果獲得批准，將有機會為歐洲患者帶來新的治療選擇。

We have also completed recruitment for our Phase 3 trial evaluating Zanidatamab and first line GEA and expect top line PFS data later this year. The overall development program for Zanidatamab includes multiple registration enabling trials, including pivotal trials in first line BTC, first line GEA, advanced breast cancer, and in a pan tumor basket trial, focused on areas where we believe Zani has the potential to emerge as the preferred HER2-targeted therapy. This comprehensive development program underscores our confidence in Zanidatamab's potential.

我們也完成了評估 Zanidatamab 和一線 GEA 的 3 期試驗的招募，預計今年稍後將獲得頂級 PFS 數據。Zanidatamab 的整體開發計劃包括多項註冊試驗，包括一線 BTC、一線 GEA、晚期乳癌和泛腫瘤籃子試驗的關鍵試驗，重點關注我們認為 Zani 有可能成為首選 HER2 標靶治療的領域。這項綜合開發計劃凸顯了我們對 Zanidatamab 潛力的信心。

Turning to slide 15, we're also very excited that the Chimerix transaction has been completed. I'm thrilled to welcome our new colleagues to Jazz. Our team is now engaged and working toward the shared goal of delivering Dordaviprone to patients.

翻到第 15 張投影片，我們也非常高興 Chimerix 交易已經完成。我很高興歡迎我們的新同事加入 Jazz。我們的團隊現在正致力於實現向患者提供 Dordaviprone 的共同目標。

Dordaviprone is a groundbreaking first-in-class small molecule in development for H3-K27 and mutant diffuse glioma, a rare high grade brain tumor that most commonly affects children and young adults. There are currently no approved drug therapies for these patients, and the median overall survival from diagnosis is approximately only one year. Multiple clinical studies have demonstrated Dordaviprone's benefit in patients with recurrent H3-K27 and mutant diffuse glioma, both as monotherapy, pending combination with other treatment approaches, including radiation, with a consistently favorable safety profile.

Dordaviprone 是一種突破性的一流小分子，用於治療 H3-K27 和突變型瀰漫性膠質瘤，這是一種最常見於兒童和年輕人的罕見高級別腦腫瘤。目前尚無針對這些患者的核准藥物療法，從診斷開始的中位總存活期僅為約一年。多項臨床研究已證明 Dordaviprone 對復發性 H3-K27 和突變型瀰漫性膠質瘤患者有益，無論是作為單一療法，還是與包括放射在內的其他治療方法相結合，都具有始終良好的安全性。

The FDA has accepted an NDA for Dordaviprone, seeking accelerated approval for treatment of H3-K27 and mutant diffuse glioma in adult and pediatric patients with progressive disease following prior therapy. The application has been granted priority review and assigned a PDUFA target action date of August 18 of this year.

FDA 已接受 Dordaviprone 的 NDA，尋求加速批准其用於治療先前接受治療後病情進展的成人和兒童患者的 H3-K27 和突變型瀰漫性膠質瘤。該申請已獲得優先審查，並指定了 PDUFA 目標行動日期為今年 8 月 18 日。

Based on communication with the FDA to date, we do not expect the agency to hold an oncology drug advisory committee meeting in connection with the review of the NDA. Beyond the recurrent disease setting, Dordaviprone is being studied in the ongoing Phase 3 action trial, evaluating its use in newly diagnosed H3-K27M mutant diffuse glioma patients following radiation treatment.

根據迄今為止與 FDA 的溝通，我們預計該機構不會就 NDA 的審查召開腫瘤藥物諮詢委員會會議。除了復發性疾病之外，Dordaviprone 正在進行 3 期臨床研究，評估其在放射治療後新診斷的 H3-K27M 突變型瀰漫性膠質瘤患者中的應用。

This trial has the potential to confirm the clinical benefit of Dordaviprone in recurrent H3-K27M mutant diffuse glioma and potentially extend this treatment option into the frontline setting. We believe that Dordaviprone has the potential to transform the standard of care for this underserved patient population with very limited treatment options.

該試驗有可能證實 Dordaviprone 對復發性 H3-K27M 突變型瀰漫性膠質瘤的臨床益處，並可能將此治療方案擴展到第一線治療。我們相信，Dordaviprone 有潛力改變這個治療選擇非常有限的醫療資源匱乏的患者群體的護理標準。

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

現在，我將把電話轉給菲爾，詢問財務更新。

Thanks, Rob.

謝謝，羅布。

I'll start with our top line results on slide 17. As a reminder, our full financial results are available in our press release, which is available today, and in our 10-Q, which will be filed tomorrow morning.

我將從第 17 張投影片上的頂線結果開始。提醒一下，我們的完整財務表現可在我們今天發布的新聞稿和明天早上提交的 10-Q 報告中查看。

In the first quarter of 2025, we recorded $898 million in total revenues. I'll note our first-quarter revenues have historically been affected by several factors, including reauthorizations and inventory bill in the latter part of the prior year, which typically burns off in the first half of the following year. As Renee mentioned, for Epidiolex, we saw more of this burn in the first quarter of this year. Despite these factors, Zywav and Epidiolex revenues grew 9% and 10% year over year, respectively.

2025 年第一季度，我們的總營收為 8.98 億美元。我要指出的是，我們的第一季收入歷來受到多種因素的影響，包括前一年下半年的重新授權和庫存帳單，這些費用通常會在下一年上半年消耗殆盡。正如蕾妮所提到的，對於 Epidiolex，我們在今年第一季看到了更多的燒傷。儘管有這些因素，Zywav 和 Epidiolex 的營收仍分別年增 9% 和 10%。

Our oncology products experienced a decline relative to the first quarter of 2024. In part, this was driven by having one fewer shipping week in the first quarter of 2025 compared to the first quarter of 2024. In addition, the decline was primarily driven by our two largest oncology products, Zepzelca and Rylaze. As Renee noted earlier, we believe we have a line of sight into our assumption of growth for these products in the coming quarters.

我們的腫瘤產品相對於 2024 年第一季有所下降。部分原因是，與 2024 年第一季相比，2025 年第一季的航運週數減少了一周。此外，銷售量下降的主要原因是我們最大的兩種腫瘤產品 Zepzelca 和 Rylaze。正如 Renee 之前提到的，我們相信我們對未來幾季這些產品的成長預測是有目共睹的。

As I'll highlight on the next slide, we are affirming our total revenue guidance for 2025 based on our conviction and the strength of our overall commercial portfolio. Adjusted net income and earnings per share in the first quarter of this year were impacted by a charge related to certain Xyrem antitrust litigation settlements. This $172 million charge to SG&A in the first quarter reduced our adjusted net income by $146 million and our GAAP and non-GAAP EPS by $2.38 per share and $2.34 per share respectively.

正如我在下一張投影片中所強調的那樣，我們根據我們的信念和整體商業組合的實力確認了 2025 年的總收入指引。今年第一季的調整後淨收入和每股收益受到與某些 Xyrem 反壟斷訴訟和解相關的費用的影響。第一季 1.72 億美元的銷售、一般及行政費用導致我們的調整後淨收入減少了 1.46 億美元，GAAP 和非 GAAP 每股收益分別減少了 2.38 美元/股和 2.34 美元/股。

Before discussing our updated 2025 financial guidance, I'd like to comment on tariffs. Now I'm sure we'll have several questions on this topic during the Q&A session. I'd limit my commentary to the most essential items.

在討論我們更新的 2025 年財務指導之前，我想先對關稅發表評論。現在我相信在問答環節我們會就這個主題提出幾個問題。我的評論僅限於最重要的內容。

I'll start with the tariffs already enacted on China, Mexico, and Canada, as well as the general 10% tariff levied more broadly. For 2025, we anticipate no direct financial impact from these tariffs and currently expect any indirect impact resulting in inflation on goods we purchase can be managed within our existing internal budgets and external guidance. We won't speculate on the potential impact of future tariffs on pharmaceutical products imported into the US at some hypothetical rate.

我首先要談的是已經對中國、墨西哥和加拿大實施的關稅，以及更廣泛徵收的 10% 的一般關稅。到 2025 年，我們預計這些關稅不會對財務產生直接影響，目前預計導致我們購買的商品通貨膨脹的任何間接影響都可以在我們現有的內部預算和外部指導範圍內進行管理。我們不會以某種假設的比率推測未來關稅對進口到美國的藥品的潛在影響。

As you expect, we've evaluated various scenarios and are positioned to come in a timely manner if and when such tariffs are enacted. I can say we have sufficient inventory in the US to serve all or nearly all of our 2025 needs for each of our products. Consequently, we expect that any impact for 2025 financials would be de minimis, if any, and unlikely to affect our guidance.

正如您所期望的，我們已經評估了各種情況，並準備在這些關稅頒佈時及時採取行動。我可以說，我們在美國有足夠的庫存來滿足我們每種產品的全部或幾乎所有 2025 年的需求。因此，我們預計，對 2025 年財務狀況的任何影響都將是微不足道的，並且不太可能影響我們的指導。

With that context, let's move to our updated 2025 financial guidance. Now at first glance, the updates may seem complex. In reality, there are three drivers for the updates, and I think you'll find they're pretty straightforward.

在此背景下，讓我們來看看更新後的 2025 年財務指引。現在乍一看，這些更新可能看起來很複雜。實際上，有三個更新驅動程序，我想你會發現它們非常簡單。

Those three drivers are the Chimerix acquisition, certain Xyrem antitrust litigation settlements, and slightly revised expectations for full year R&D expense.

這三個驅動因素分別是 Chimerix 收購、某些 Xyrem 反壟斷訴訟和解以及對全年研發費用的略微修改的預期。

The Chimerix acquisition affects guidance in three ways. First, it will be accounted for as an asset acquisition. Consequently, we'll recognize a non-tax deductible required IPR&D charge that we estimate will be between $870 million and $900 million. Second, we'll recognize Chimerix's results from operations from the date of close to the end of the year.

Chimerix 的收購從三個方面影響了指導。首先，它將被視為一項資產收購。因此，我們將確認一項不可免稅的智慧財產權與開發費用，估計該費用將在 8.7 億美元至 9 億美元之間。其次，我們將確認 Chimerix 從接近年底的日期開始的營運表現。

At a high level, this includes a non-material amount of revenue and cost of sales, as well as roughly $50 million in SG&A expenses and roughly $60 million in R&D expenses. Third, our interest expense and interest income expectations have been adjusted to reflect the timing of the net outlay for Chimerix, which is approximately $890 million as well as the continued investment in Chimerix's operations over the remainder of the year.

從高層次來看，這包括非實質的收入和銷售成本，以及約 5,000 萬美元的銷售、一般及行政費用和約 6,000 萬美元的研發費用。第三，我們對利息支出和利息收入預期進行了調整，以反映 Chimerix 淨支出的時間（約為 8.9 億美元）以及今年剩餘時間對 Chimerix 營運的持續投資。

Moving to the Xyrem anti-trust litigation settlements, our 2025 guidance has been updated to reflect the tax-deductible charge of $172 million we recognize in our SG&A expenses in the first quarter.

轉向 Xyrem 反壟斷訴訟和解，我們的 2025 年指引已更新，以反映我們在第一季度的銷售、一般及行政費用中確認的 1.72 億美元的稅收抵扣費用。

Finally, excluding Chimerix, our guidance has been adjusted to reflect slightly lower R&D excess, roughly $20 million in aggregate, in our existing Jazz portfolio, driven primarily by the successful early conclusion of two Phase 4 Zywav studies.

最後，不包括 Chimerix，我們的指導方針已進行調整，以反映我們現有 Jazz 產品組合中略低的研發超額，總計約 2000 萬美元，這主要得益於兩項 4 期 Zywav 研究的成功提前結束。

Moving on to the slides that illustrate the specific provisions to our guidance, you'll see on slide 18 that we are affirming our full year 2025 revenue guidance. Our guidance range remains $4.15 billion to $4.4 billion which represents 5% year -over-year growth with the midpoint. This is driven by our confidence in both the neuroscience and oncology portfolios. As Zywav continues to grow with impressive new patient adds and expansion of the IH market, we continue to expect that Epidiolex will reach blockbuster status in 2025 and anticipate why those revenues will normalize during the second quarter of 2025.

繼續查看說明我們指南具體條款的幻燈片，您會在第 18 張投影片上看到我們確認了 2025 年全年收入指南。我們的指導範圍仍然是 41.5 億美元至 44 億美元，中間值年增 5%。這是由我們對神經科學和腫瘤學產品組合的信心所驅動的。隨著 Zywav 繼續成長，新增患者數量令人印象深刻，IH 市場不斷擴大，我們繼續預期 Epidiolex 將在 2025 年達到重磅藥物地位，並預測為什麼這些收入將在 2025 年第二季恢復正常。

We also believe that Zepzelca's potential expansion into first line maintenance therapy will provide more patients the ability to receive treatment for a longer duration.

我們也相信，Zepzelca 擴展到第一線維持治療的潛在可能性將使更多患者能夠接受更長的治療。

Turning to slide 19, our non-GAAP adjusted SG&A guidance range for $1.25 billion to $1.31 billion has been updated to $1.47 billion to $1.53 billion. The revised range reflects the $172 million pre-tax charge for this quarter associated with certain Xyrem antitrust litigation settlements and the addition of Chimerix. Our non-GAAP adjusted R&D guidance range of $720 million to $770 million has also been updated to $760 million to $810 million. This change is driven primarily by additional investment in ongoing clinical programs for Dordaviprone, partially offset by the slight reduction in spend on the Jazz portfolio I mentioned earlier.

轉到投影片 19，我們的非 GAAP 調整後銷售、一般及行政費用指引範圍從 12.5 億美元至 13.1 億美元已更新為 14.7 億美元至 15.3 億美元。修訂後的範圍反映了本季與某些 Xyrem 反壟斷訴訟和解以及 Chimerix 的加入相關的 1.72 億美元稅前費用。我們的非 GAAP 調整後研發指引範圍從 7.2 億美元至 7.7 億美元也已更新為 7.6 億美元至8.1億美元。這項變更主要是由於對 Dordaviprone 正在進行的臨床項目的額外投資所致，但部分被我之前提到的 Jazz 產品組合支出的輕微減少所抵消。

On the bottom line, we expect adjust the net income to be $250 million to $350 million for the full year of 2025. The updated ANI guidance reflects the cumulative effect of all the items I described earlier. We're in a sound financial position with healthy cash flow generation over $400 million in the first quarter, and we have several near-term commercial opportunities and a particularly important upcoming data readout.

最終，我們預計 2025 年全年淨收入將達到 2.5 億至 3.5 億美元。更新後的 ANI 指南反映了我之前描述的所有項目的累積效應。我們的財務狀況良好，第一季的現金流超過 4 億美元，我們擁有多個近期商業機會和即將發布的特別重要的數據。

We continue to believe that a disciplined approach to capital allocation, including prioritized spend on our ongoing R&D programs and lead commercial products, as well as corporate development, will drive long-term shareholder value.

我們始終相信，嚴謹的資本配置方法，包括優先投資於我們正在進行的研發項目和領先的商業產品以及企業發展，將推動長期股東價值。

I'll now turn the call back to Bruce for closing remarks.

現在我將把電話轉回給布魯斯，請他作最後發言。

I'll conclude our prepared remarks on slide 21.

我將在第 21 張投影片上結束我們的準備好的發言。

We had a strong start to 2025 with continued focus on commercial execution led by growth of Zywav and Epidiolex and the ongoing launch of Ziihera. In addition, we were pleased to close the Chimerix transaction and welcome our new colleagues as we work together to prepare for the potential launch of Dordaviprone.

我們在 2025 年取得了良好的開端，繼續專注於商業執行，以 Zywav 和 Epidiolex 的成長以及 Ziihera 的持續推出為主導。此外，我們很高興完成 Chimerix 交易並歡迎新同事的加入，共同為 Dordaviprone 的潛在上市做準備。

Corporate development remains key to our strategy, and the Chimerix transaction is representative of our ability to identify and execute transactions that are strong strategic fits. Dordaviprone is a potential near-term commercial opportunity with an efficient commercial call point and durable revenue stream.

企業發展仍然是我們策略的關鍵，而 Chimerix 交易代表了我們識別和執行具有強大策略契合度的交易的能力。Dordaviprone 是一個潛在的近期商業機會，具有高效的商業呼叫點和持久的收入來源。

Our R&D pipeline continues to advance with the top line PFS readout from our Phase 3 GEA trial of Zanidatamab expected in the second half of 2025, the near-term PDUFA date of Dordaviprone in August, and the recent submission of the Zepzelca FNDA.

我們的研發管道繼續推進，預計 2025 年下半年將獲得 Zanidatamab 的 3 期 GEA 試驗的頂線 PFS 讀數，Dordaviprone 的近期 PDUFA 日期為 8 月，並且最近提交了 Zepzelca 的 FNDA。

Our financial position, balance sheet, and cash flow generation remains strong, supported by our focus on operational excellence and strategic capital allocation. We remain well positioned to continue delivering innovative therapies that transform the lives of patients and their families.

由於我們注重卓越營運和策略資本配置，我們的財務狀況、資產負債表和現金流量產生仍然強勁。我們始終處於有利地位，能夠持續提供創新療法，改變患者及其家人的生活。

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

我們的準備好的演講到此結束。現在我想將電話轉給接線員，開通問答專線。

(Operator Instructions) Jason Gerberry, Bank of America.

（操作員指示）美國銀行 Jason Gerberry。

Hey, guys, thanks for taking my question. And so I'm going to respect Phil's comment about not asking to speculate on tariffs, but what I'm going to ask is about your supply chain and specifically Zywav, so you have a US CDMO and so I'm just curious if you can speak to -- Zywav is not a very high-volume product, so just curious to the extent that, if need be in 2026, you could fully supply the product from your US CDMO? And if you can comment if your API can be sourced in the US that you've got a fully US supplied product for the US market? Thanks.

嘿，夥計們，謝謝你們回答我的問題。因此，我尊重 Phil 關於不要求推測關稅的評論，但我想問的是關於您的供應鏈，特別是 Zywav，所以您有一個美國 CDMO，所以我很好奇您是否可以談談 - Zywav 不是一種產量很大的產品，所以我只是好奇，如果需要的話，在 2026 年，您可以從您的美國 CDMO 完全供應產品嗎？並且，如果您能評論一下您的 API 是否可以在美國採購，您是否有完全由美國供應的產品供應給美國市場？謝謝。

Yeah, Jason, thanks for the question and I appreciate your being respectful of the prior comments as well. We can't comment on what we can't.

是的，傑森，謝謝你的提問，我也謝謝你尊重之前的評論。我們不能評論我們不能評論的事情。

So you're correct, we do have a US supplier for oxybate, including Zywav. That supplier does have enough capacity that we can access to fully meet our US needs, and certainly, if tariffs are coming into play would be a very effective option for us to mitigate that exposure, and there's no particular issues that I would note with regard to API and having that subject to tariff.

所以您說得對，我們確實有一個美國的羥基丁酸鹽供應商，包括 Zywav。供應商確實擁有足夠的產能，我們可以充分利用這些產能來完全滿足我們在美國的需求，而且，如果關稅開始發揮作用，這對我們來說將是一個非常有效的選擇，以減輕這種風險，而且在 API 和關稅方面我沒有註意到任何特別的問題。

Okay, the next caller, please.

好的，請下一位來電者。

Jessica Fye, JPMorgan.

潔西卡費伊（Jessica Fye），摩根大通。

Hey, guys, good afternoon. Thanks for taking my question. So following up on the first question, maybe thinking beyond oxybate, can you talk about Jazz's manufacturing footprint, including sources of API and any other possible mitigation strategies or contingency plans to neutralize any potential impact of biopharma tariffs if they're implemented?

嘿，大家下午好。感謝您回答我的問題。因此，繼續第一個問題，也許除了考慮羥基丁酸鹽之外，您能否談談 Jazz 的製造足跡，包括 API 來源以及任何其他可能的緩解策略或應急計劃，以抵消生物製藥關稅實施後可能產生的影響？

Maybe I'll ask Renee to take the first part of that, which is just factually where we do our manufacturing, and then Phil, if you want to add anything more on tariffs, jump in.

也許我會請蕾妮 (Renee) 談談第一部分，也就是我們實際生產的地方，然後菲爾 (Phil)，如果你想補充有關關稅的更多信息，請隨時提問。

Sure, Bruce, and thanks for the question, Jess. So with respect to where we manufacture Zywav and Xyrem, Phil mentioned we do have a CMO in the US. We also have a facility in Athlone, Ireland, and so we do have a level of flexibility there. With respect to Epidiolex, we have a facility in the UK where we produce that product and we have the capability to also develop other products at that plant and then some of our other smaller products on the oncology side are manufactured in different locations and Defitelio, in Villa Guardia, Italy.

當然，布魯斯，謝謝你的提問，傑西。因此，關於我們在哪裡生產 Zywav 和 Xyrem，Phil 提到我們在美國確實有 CMO。我們在愛爾蘭阿斯隆也設有工廠，因此我們在那裡具有一定的靈活性。關於 Epidiolex，我們在英國設有一家工廠，專門生產該產品，並且我們還有能力在該工廠開發其他產品，而我們在腫瘤學方面的一些其他小型產品則在不同地點生產，其中包括位於意大利 Villa Guardia 的 Defitelio。

[Visios] is manufactured by Symetra and then Rylaze is manufactured in Denmark. So we do have quite a lot of manufacturing in Europe. In terms of our capabilities and what options we have going forward, obviously making changes to our manufacturing sources is something that we don't take lightly. It does take a period of time, but we do have a level of flexibility, as we've mentioned today with our oxybate products, and we'll continue to evaluate both backup options and other sources of manufacturing.

[Visios] 由 Symetra 製造，Rylaze 在丹麥製造。所以我們在歐洲確實有相當多的製造業。就我們的能力和未來的選擇而言，顯然我們不會輕易改變我們的製造來源。這確實需要一段時間，但我們確實具有一定程度的靈活性，正如我們今天提到的氧化物產品一樣，我們將繼續評估備用選項和其他製造來源。

Yeah, it's a great summary and as you'd expect, Jess, this has been subject of quite a bit of work across functional team since sort of late last year, early this year, and there certainly are opportunities for us to work with CMOs here in the US to further reduce the exposure to Jazz beyond those that we're currently working with to date for the primary way that we've buffered impact would be through having sufficient inventory in market here in the US to cover all or nearly all of our US needs at this point for 2025 for each of our products.

是的，這是一個很好的總結，正如你所期望的，傑西，自去年年底今年年初以來，這已經成為職能團隊大量工作的主題，我們當然有機會與美國的 CMO 合作，進一步減少對 Jazz 的曝光，除了我們目前正在合作的那些之外，我們緩衝影響的主要方式是通過在美國市場上擁有足夠的所有庫存，以滿足我們目前正在合作的那些之外，我們緩衝影響的主要方式是通過在美國市場上擁有足夠的所有庫存，以滿足我們目前在 2025 年每個美國的全部。

We'll continue with that strategy, then obviously depending upon if and when tariffs come into effect what geographies they would impact and what rate, we may have some protection from inventory for 2026 as well.

我們將繼續實施此策略，然後顯然取決於關稅是否生效以及何時生效、將對哪些地區產生影響以及稅率如何，我們可能也會對 2026 年的庫存提供一些保護。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

I actually wanted to ask a question about Zepzelca and competition from IMDELLTRA. I know it's having an impact and the label expansion is certainly not lost on me, but I guess my question here is, how should we think about Zepzelca over time in terms of its trajectory? Do you anticipate that first line contribution will overwhelm the pressure in the second line setting?

我實際上想問一個關於 Zepzelca 和 IMDELLTRA 競爭的問題。我知道它正在產生影響，我當然也意識到了品牌擴張，但我想我的問題是，我們應該如何看待 Zepzelca 的發展軌跡？您是否預期第一線的貢獻將壓倒第二線的壓力？

And then also how are you thinking about the expansion of IMDELLTRA itself bearing in mind that Amgen has a pretty comprehensive development program in small cell lung in terms of earlier lines of therapy? So how are you thinking about Zepzelca overall as a growth product going forward? Thanks.

那麼，考慮到安進在早期治療方面在小細胞肺方面擁有相當全面的開發計劃，您如何看待 IMDELLTRA 本身的擴展？那麼，您如何看待 Zepzelca 作為未來成長產品的整體表現？謝謝。

Yeah, I'm happy to jump in and take that one. So as we think about Zepzelca, we did have some dynamics impacting the first quarter. As we look forward though to your point on Zepzelca returning to growth, even with competition and some delayed progression of first-line limited stage patients coming into the second line, Zepzelca in the second line still remains the leading treatment as measured by market share.

是的，我很高興加入並接受這個。因此，當我們考慮 Zepzelca 時，我們確實有一些動態影響第一季。我們期待您對 Zepzelca 恢復成長的觀點，即使存在競爭，且一線有限期患者進入二線治療的進展有所延遲，但以市​​場份額衡量，二線治療中的 Zepzelca 仍然是領先的治療藥物。

Importantly, we do look forward to both sharing our data at ASCO on the first line and forte trial where we showed stats and clinically meaningful PFS and OS in our study of first line extensive stage maintenance patients and so this is something we look forward presenting at ASCO and then rapidly submitting that data for potential inclusion in NCCN treatment guidelines.

重要的是，我們確實期待在 ASCO 上分享我們關於一線治療和 forte 試驗的數據，我們在對一線廣泛期維持患者的研究中展示了統計數據和具有臨床意義的 PFS 和 OS，因此，我們期待在 ASCO 上展示這些內容，然後迅速提交這些數據，以便將其納入 NCCN 治療指南。

We do expect this data to be practice changing and therefore going into the first line, we look to a larger patient population to treat in the extensive stage patients, but also longer treatment duration. So we do expect this to contribute to future growth of the brand, and we would also expect patients that didn't receive Zepzelca in first line to have the opportunity to receive it in the second line.

我們確實希望這些數據能夠改變實踐，因此進入第一線，我們期待更大的患者群體來治療廣泛期患者，同時也延長治療時間。因此，我們確實希望這將有助於該品牌的未來成長，並且我們也希望那些未在第一線接受 Zepzelca 治療的患者有機會在第二線接受該治療。

And then, Rob, do you want to take the question with respect to the views of Tarlatamab going forward from a clinical perspective?

然後，羅布，你想從臨床角度回答有關 Tarlatamab 未來發展的觀點的問題嗎？

Yeah, again, yes, I think you covered it very well, Renee, with our new data and ultimately adoption into NCCN and in the label as first line. That affords us a larger population for a longer duration of therapy. Tarlatamab's not approved in that setting and it would be quite a while before a new trial would read out there.

是的，是的，我認為你很好地涵蓋了這一點，蕾妮，我們的新數據最終被納入 NCCN 並作為第一行標籤。這使我們能夠為更多的患者提供更長時間的治療。Tarlatamab 尚未獲得批准，而且新的試驗結果還需要相當長一段時間才能公佈。

So I think that's the -- as a new standard of care, I think that's the key, that extensive stage patients who don't progress after induction, as you said, should become the standard of care to get Zepzelca. And then for patients who don't receive it in front lines of Zepzelca, it has data to show that it's an effective second line therapy.

所以我認為這是——作為一種新的護理標準，我認為這是關鍵，正如你所說，誘導後沒有進展的廣泛期患者應該成為獲得 Zepzelca 的護理標準。對於未接受 Zepzelca 一線治療的患者，有數據顯示它是一種有效的二線療法。

Marc Goodman, Leerink Partners.

馬克古德曼（Marc Goodman），Leerink Partners。

Your comments about tariffs not impacting 2025, I assume has to do with the fact that you have inventory that you've just built up in the US and so you don't have to worry about it. But is it a fair question to ask what would be the impact for a full year just on an annual basis if you did have all that inventory built up? What would we be talking about here as far as the numbers?

您關於關稅不會影響 2025 年的評論，我認為與您剛剛在美國建立的庫存有關，因此您不必擔心這一點。但是，如果確實累積了那麼多庫存，那麼從年度角度來看，對全年會產生什麼影響呢？這是一個公平的問題嗎？就數字而言，我們在這裡要討論什麼？

Yeah, Mark, I appreciate the question, sort of in this theoretical realm of what might happen in the future. It depends obviously on what kind of rates being put in, what kind of geography are affected, so we're not commenting at this point in time on those hypotheticals.

是的，馬克，我很感謝你提出這個問題，從理論角度來說，未來可能會發生什麼。這顯然取決於採用何種稅率、何種地理區域會受到影響，因此我們目前不對這些假設發表評論。

I would say again, depending on when tariffs will go into effect if they are, we could get some coverage from inventory as we're getting effectively this year. And then we also have the ability for our oxybate products to use the US source to effectively mitigate that exposure. Beyond that, the main tools available to us would be things like looking to work with other third-party manufacturers here in the US to further reduce the impact but feel very good about the position that we're in currently, obviously closely monitoring the situation and we'll take actions as needed.

我想再說一遍，這取決於關稅何時生效（如果生效），我們可以從庫存中獲得一些覆蓋，就像我們今年有效地獲得庫存一樣。然後，我們還可以使我們的羥基丁酸鹽產品利用美國來源來有效減輕這種暴露。除此之外，我們可以使用的主要工具是尋求與美國其他第三方製造商合作，以進一步減少影響，但我們對目前的狀況感到非常滿意，顯然我們會密切關注局勢，並根據需要採取行動。

Andrea Newkirk, Goldman Sachs.

高盛的安德里亞紐柯克 (Andrea Newkirk)。

Y'all, this is [Toan] on for Andrea. Thanks for taking our questions today. Want to understand a little bit better, why does the Chimerix acquisition make sense for Jazz and what do you find most compelling about the Dordaviprone commercial opportunity? And related to that, how are you thinking about additional BD activities going forward? Thank you.

大家好，這是 [Toan] 為 Andrea 表演的。感謝您今天回答我們的問題。想更深入地了解一下，為什麼收購 Chimerix 對 Jazz 來說有意義，以及您認為 Dordaviprone 商業機會最引人注目的是什麼？與此相關，您如何考慮未來進行其他 BD 活動？謝謝。

So maybe I'll jump in at the total company acquisition level and then Renee or Rob, if you want to add anything on Dordaviprone in particular, you can.

因此，也許我會從整個公司收購層面入手，然後 Renee 或 Rob，如果您想特別補充有關 Dordaviprone 的任何內容，您可以。

We've been, I think, pretty clear about our corporate development strategy for some time now as a major pillar of how we invest capital to create value for shareholders in addition to what we do in our investments in our commercial portfolio and in our R&D efforts. And we've been clear that our priorities include finding products that would represent, a real advance where there's unmet medical need in a serious condition that aligns with our capabilities that has an efficient commercial call point so that we don't need to do a massive buildup of commercial expense that have long durability.

我認為，一段時間以來，我們對企業發展策略一直非常清楚，除了我們在商業組合投資和研發工作中所做的投資之外，這也是我們如何投資資本為股東創造價值的主要支柱。我們已經明確表示，我們的首要任務包括尋找能夠代表真正進步的產品，滿足嚴重疾病中未滿足的醫療需求，這些產品與我們的能力相符，具有高效的商業呼叫點，這樣我們就不需要長期積累大量的商業費用。

And we really feel that Chimerix on all fronts was a perfect fit for us, matches well with what we do well, particularly in oncology, near term launch, again, efficient and we're confident it fills a serious unmet need.

我們確實覺得 Chimerix 在各方面都非常適合我們，與我們擅長的領域非常匹配，特別是在腫瘤學領域，近期上市，同樣高效，我們相信它能滿足嚴重的未滿足需求。

Rob, you want to jump in?

羅布，你想加入嗎？

Yeah, I'd love to. The treatment for diffuse glioma, hasn't changed since I trained as a pediatric oncologist 25 years ago. Patients get debulking surgery, which is never curative, and then radiation therapy. And that's essentially it prior to the Dordaviprone and prior to the discovery that H3-K27 and mutations occurred and we're a driver for oncogenesis in this setting.

是的，我很樂意。自從我 25 年前接受兒科腫瘤科醫生培訓以來，瀰漫性膠質瘤的治療方法一直沒有改變。患者接受減瘤手術，但這無法治癒疾病，然後接受放射治療。這基本上就是 Dordaviprone 之前的情況，也是在發現 H3-K27 和突變之前的情況，我們是這種環境下致癌的驅動因素。

It's been shown now with Dordaviprone that for patients with this mutation, the therapy is effective. We're really impressed with not only the efficacy but also the safety profile. And the disease setting, as I indicated, has an ongoing very high unmet need and without many other prospects, unfortunately.

目前已證明，對於患有這種突變的患者，Dordaviprone 療法是有效的。我們不僅對其功效印象深刻，而且對其安全性也印象深刻。正如我所指出的，疾病環境中存在著非常高的未滿足需求，不幸的是，也沒有太多其他前景。

Annabel Samimy, Stifel.

安娜貝爾·薩米米（Annabel Samimy），Stifel。

Hi, thanks for taking my question. So for Rylaze, I understand, obviously that the protocols have changed for the pediatric indication that delayed treatment. What can we expect for pickup in AYAs? It's been, I guess, quite a little bit of time that you've been trying to drive growth in that area? And when do you think we can get some critical mass there and some momentum to return Rylaze back to growth?

你好，謝謝你回答我的問題。因此，對於 Rylaze，我理解，顯然針對兒科適應症的治療方案已經發生了改變，從而延遲了治療。我們對 AYA 的接送有何期待？我想，您已經嘗試推動該領域的發展一段時間了？您認為我們什麼時候才能達到臨界規模並取得一些動力，讓 Rylaze 恢復成長？

Yeah, thanks for the question there. With respect to the AYA segment, it really does take time to drive education with adult treaters to use asparaginase and Rylaze. These are treaters that often have a different protocol that they're following. And so we were certainly pleased last year with the updated results from the protocol that created the gap in asparaginase treatment because although it created a delay in when asparaginase is dosed and it has led to some of the challenges that we've had with revenues, we feel very confident that it is demonstrating the importance of asparaginase to treatment, and it's also resulted in much higher overall survival, which is good news for patients.

是的，謝謝你的提問。就 AYA 領域而言，確實需要時間來推動對成年治療者使用天冬酰胺酶和 Rylaze 的教育。這些治療師通常遵循不同的治療方案。因此，我們對去年在天冬酰胺酶治療中造成差距的方案的最新結果感到非常滿意，因為儘管它延遲了天冬酰胺酶的給藥時間並導致了我們在收入方面遇到的一些挑戰，但我們非常有信心，它證明了天冬酰胺酶對治療的重要性，並且它還帶來了更高的總體生存率，這對患者來說是個好消息。

So we are having some momentum and success with respect to the AYA segment. It does take a little bit more time than what we see in pediatrics where we've had pretty much universal adoption. But there has been some delay in getting back to that continued use. Importantly, as we've said before, there is no change to the total doses of asparaginase with the new protocol that is in place, and so we expect we will be getting back to normalization in the second quarter and can continue to focus on the growth in AYA.

因此，我們在 AYA 領域取得了一些進展並取得了成功。與兒科普遍採用的方法相比，這種方法確實需要更多時間。但恢復持續使用已經有些延遲。重要的是，正如我們之前所說，新方案對天冬酰胺酶的總劑量沒有影響，因此我們預計第二季將恢復正常，並可以繼續關注 AYA 的成長。

Maybe before we go to the next call, I can just add something real quick. Annabel, if you think about our oncology performance year over year here in the first quarter, I think it's important to keep in mind what I've mentioned about there being one fewer shipping week effectively in the first quarter of this year, probably it's hard to know when you have an additional week, you're getting that at an average rate higher or lower.

也許在我們進行下一次通話之前，我可以快速補充一些內容。安娜貝爾，如果你想想我們第一季度的腫瘤學同比表現，我認為重要的是要記住我提到的今年第一季度的運輸週實際上減少了​​一周，可能很難知道當你有額外的一周時，你得到的平均費率是更高還是更低。

But just on pure math, missing one out of 13 is 7.7% or roughly 8% of the opportunity. So certainly there was an impact on the year-over-year growth just given the fact that we had one fewer shipping day. So keep that in mind if you think about the trends and what you're seeing.

但僅從純數學角度來看，錯過 13 個中的 1 個就佔 7.7% 或大約 8% 的機會。因此，考慮到我們的運輸日減少了一天，這肯定會對同比增長產生影響。因此，當您思考趨勢和所看到的情況時，請記住這一點。

Go to the next caller, please.

請接聽下一位來電。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞。

Hey, this is [Amy] on for Akash. Thanks so much for taking our question. Just one for HERIZON-GEA. Would love to get your expectations on the control on performance and what gives you confidence that KEYNOTE isn't outperforming what was shown with KEYNOTE-811? Thanks so much.

嘿，我是 Akash 的 [Amy]。非常感謝您回答我們的問題。僅針對 HERIZON-GEA 一個。很想了解您對效能控制的期望，以及是什麼讓您相信 KEYNOTE 的表現不會超越 KEYNOTE-811 所展現的表現？非常感謝。

Yeah, so there's been quite a bit of experience in this first line HER2 positive GEA setting, from the original ToGA trial that was the basis for the approval of Herceptin through the Jacob trial and then more recently KEYNOTE-811. And across those studies, the control arm of trastuzumab chemotherapy has performed pretty consistently with a medium PFS between, I think, about 6.9 months up to a high of about 8.1 months in the more modern era.

是的，因此，在 HER2 陽性 GEA 的一線治療中已經有了相當多的經驗，從最初的 ToGA 試驗（這是赫賽汀獲批的基礎）到 Jacob 試驗，再到最近的 KEYNOTE-811。在這些研究中，曲妥珠單抗化療的對照組表現相當穩定，我認為平均 PFS 介於約 6.9 個月到更現代的約 8.1 個月之間。

So through these three Phase 3 trials, I think it gives us a pretty good idea of what to expect from the control arm. And we planned accordingly. We continue to have confidence in Zanidatamab's ability here. As you know, there have been two Phase 2s published showing very promising results. Zani chemo with a medium PFS of 15.2 months. That's the last publication of Zani chemo to [Zanidatamab] with a median PFS of 16.7 months.

因此，透過這三個第三階段試驗，我認為我們可以很好地了解對照組的預期結果。我們也制定了相應的計劃。我們繼續對 Zanidatamab 的能力充滿信心。如您所知，目前已發布了兩個第二階段的研究成果，並顯示出非常有希望的結果。Zani 化療的平均 PFS 為 15.2 個月。這是 Zani 化療與 [Zanidatamab] 的最新出版物，中位 PFS 為 16.7 個月。

And at ASCO this year, we will update for the first time, the overall survival data with Zani chemo prior to this, the medium wasn't estimatable based on the maturity level. We look forward to presenting those data as well.

在今年的 ASCO 上，我們將首次更新先前 Zani 化療的整體存活數據，根據成熟度水平無法估計中位數存活期。我們也期待展示這些數據。

Joseph Thome, TD Cowen.

約瑟夫·托米（Joseph Thome），考恩（Cowen）TD。

Thank you for taking my question. On Dordaviprone, I think Chimerix paused enrollment in the Phase 3 study ahead of the acquisition. So kind of just curious if that has restarted and if you anticipate making any changes to the Phase 3 trial in the first line patients?

感謝您回答我的問題。關於 Dordaviprone，我認為 Chimerix 在收購之前暫停了第三階段研究的招募。所以我只是好奇這是否已經重新開始，以及您是否預計會對一線患者的 3 期試驗做出任何改變？

And maybe relatedly, obviously a lot of shakeups at the FDA, I guess what kind of data points can you provide to make sure that everything is on track with the upcoming PDUFA date, especially given Chimerix that do a little bit of a 180 on the submission? Thank you.

也許與此相關的是，FDA 顯然發生了很多變動，我想您能提供什麼樣的數據點來確保一切都按照即將到來的 PDUFA 日期進行，特別是考慮到 Chimerix 在提交時做了 180 度的大轉變？謝謝。

Yeah, I'm happy to take those. So with regard to the FDA, so far, the review is going exactly as we expect, no surprises there and no indication that we would be off of our PDUFA date of August 18.

是的，我很樂意接受這些。因此，就 FDA 而言，到目前為止，審查進展完全符合我們的預期，沒有任何意外，也沒有跡象表明我們將偏離 8 月 18 日的 PDUFA 日期。

The first part of your question was related to pausing enrollment in the ongoing confirmatory frontline trial and just to clarify, that was posed only in the US and there we were anticipating an approval and availability of drugs and therefore, we want to avoid the problem of patients enrolling and then crossing over from the control arm to get Dordaviprone by prescription, which could confound the overall survival results.

您問題的第一部分與暫停正在進行的確認性一線試驗的招募有關，需要澄清的是，這僅在美國提出，我們預計藥物會獲得批准和供應，因此，我們希望避免患者招募後從對照組轉到通過處方獲得 Dordaviprone 的問題，這可能會影響總體生存結果。

As you mentioned, while the trial isn't growing very well, we would have time potentially to make changes to the analysis plan. We haven't announced any of those changes, but certainly, we'll look at that carefully to be sure that that trial is well powered to deliver the results not only in a timely fashion, but that would be most informative.

正如您所說，雖然試驗進展不太順利，但我們可能有時間對分析計劃進行更改。我們尚未宣布任何這些變化，但當然，我們會仔細研究，以確保該試驗不僅能夠及時提供結果，而且還能提供最具參考價值的資訊。

Gregory Renza, RBC Capital Markets.

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

Hey, good evening, guys. Thanks for taking my question. My question is just on the oxybates, and Renee, you were articulating just some effectiveness on the campaigns and how those are performing well. I just wanted you to give an opportunity to elaborate a little bit about what you're seeing and what the direct impacts are from the campaigns that have led to your reassurance about the contribution and the growth of the IH market? Thanks so much.

嘿，大家晚上好。感謝您回答我的問題。我的問題只是關於羥基巴特類藥物，蕾妮，您只是闡明了這些活動的一些有效性以及它們的表現如何。我只是想讓您有機會詳細說明您所看到的情況，以及這些活動產生的直接影響是什麼，讓您對智慧家庭市場的貢獻和成長充滿信心？非常感謝。

Thanks for the question. So we are seeing beneficial response to the campaigns. We're seeing as we are building in particular the idiopathic hypersomnia market, we are seeing our disease education and continued interactions with physicians helping them to better identify idiopathic hypersomnia. It also helps patients to better understand this condition, for which there has not been a lot of disease awareness in the past because without an approved medication, there's not a lot of incentive to actually diagnose someone with idiopathic hypersomnia.

謝謝你的提問。因此，我們看到了對這些活動的積極回應。我們看到，隨著我們特別建立特發性嗜睡症市場，我們看到我們的疾病教育和與醫生的持續互動幫助他們更好地識別特發性嗜睡症。它還可以幫助患者更好地了解這種疾病，過去人們對這種疾病的認識並不多，因為在沒有批准的藥物的情況下，沒有太多動力去真正診斷某人是否患有特發性嗜睡症。

So not only have we had good success with the digital and media campaigns that I mentioned, but we've continued to sharpen our execution in the field. We have continued to grow new prescribers, we've had great success with our field nurse educator program, and we've had another -- sorry, a number of other initiatives that are proving effective and really give us confidence in the growth.

因此，我們不僅在我提到的數位和媒體活動方面取得了巨大成功，而且我們還繼續加強了該領域的執行力。我們繼續增加新的處方人員，我們的現場護理教育者計劃取得了巨大成功，並且我們還有其他一些舉措，這些舉措被證明是有效的，並真正讓我們對增長充滿信心。

If you look at where we ended this quarter, this first quarter of 2025, and compare that to where we were a year ago, stepping out of the first quarter of 2024, looking at the patient adds, we've seen an increase of 5%, and that is in a mature market with competition, which is really great progress.

如果您看看我們本季度，也就是 2025 年第一季度結束時的情況，並將其與一年前的情況進行比較，走出 2024 年第一季度，看看患者增加的情況，我們已經看到 5% 的增長，而且這是在一個競爭激烈的成熟市場中，這確實是一個很大的進步。

Then with idiopathic hypersomnia, we've had an increase of 39% looking at the progress over the last 12 months. So we're really excited about the continued momentum that we have. Certainly, we have seasonality each year in the first quarter, but still executing really well in this area.

然後，對於特發性嗜睡症，從過去 12 個月的進展來看，發病率增加了 39%。因此，我們對持續的發展勢頭感到非常興奮。當然，每年第一季我們都會經歷季節性變化，但我們在這一領域的表現仍然非常好。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi, thanks for taking the question. In Dordaviprone, can you discuss a little bit more about where it could fit in the treatment algorithm initially upon approval, and then also when could the first results come from the action trial that might affect how it's used?

你好，謝謝你回答這個問題。在 Dordaviprone 中，您能否進一步討論它在獲得批准後最初在治療演算法中的位置，以及何時可以從可能影響其使用方式的行動試驗中獲得第一批結果？

Yes, so we expect, based on the submission that we've made, we expect the initial accelerated approval to be in the recurrent setting. The action trial, as you know, is treating in the frontline setting after patients received the bulking surgery and radiation therapy, and that will give us an opportunity to expand to the front line. We haven't given specific dates on when that would read out, but we have said it's enrolling to plan.

是的，因此，根據我們提交的內容，我們預計最初的加速批准將以重複的方式進行。如您所知，該行動試驗是在患者接受增大手術和放射治療後在前線環境中進行治療，這將使我們有機會擴展到前線。我們還沒有給出具體的日期，但我們表示正在按計劃進行招生。

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Hi thanks for taking my question. Can you provide us with an update on JzP441, where you are with the NT1 study and then when we might get an update on that? And then just more broadly touching upon the comments previously around business development, have your priorities changed or evolved in the last couple of months as we've seen the market change? And if you could sort of comment on what types of assets, whether it's by the therapeutic area or the stage of development you'd be focused on if you think about adding something inorganically?

你好，謝謝你回答我的問題。您能否向我們提供有關 JzP441 的最新消息，以及您對 NT1 研究的進展情況，以及我們何時可以獲得有關該研究的最新消息？然後更廣泛地談到先前有關業務發展的評論，隨著市場的變化，過去幾個月您的優先事項是否發生了變化或發展？如果您可以評論一下，如果您考慮添加一些無機物質，您會關注哪些類型的資產，無論是治療領域還是開發階段？

Thank you.

謝謝。

I'm just going to remind people try to limit it to one question, but on this one, maybe Rob, you could talk about 441 and then Phil, if you want to jump in on corporate development priorities.

我只是想提醒大家盡量將其限制在一個問題上，但在這個問題上，也許 Rob，你可以談談 441，然後 Phil，如果你想加入企業發展重點的話。

Yeah, we have initiated the 441 trial, which I'll remind you is intended to be in a small number, approximately 10 patients with NT1, and we expect to look at those data as they come in, but we haven't given any specific guidance on when we would share information on those data just as yet.

是的，我們已經啟動了 441 試驗，我要提醒您的是，該試驗的參與人數很少，大約有 10 名 NT1 患者，我們希望在這些數據出來後查看它們，但我們還沒有給出關於何時分享這些數據信息的具體指導。

Yeah, I'm sorry, the second part of the question. So for corporate development, priorities are unchanged. We continue to look at corporate development as a very important way for us to go ahead and reach more patients over time, create value for shareholders. We finished the first quarter in a really strong financial position with $2.6 billion in cash investments, $430 million in operating cash flow in the quarter.

是的，抱歉，這是問題的第二部分。因此對於企業發展而言，優先事項是不變的。我們始終將企業發展視為我們不斷前進、隨著時間的推移接觸更多患者、為股東創造價值的重要途徑。我們第一季的財務狀況非常強勁，本季現金投資額為 26 億美元，營運現金流為 4.3 億美元。

So even after the payment of roughly $890 million net to acquire Chimerix, we're in a really strong position to continue to invest in our future. We do look across the various therapeutic areas that we're currently in, as well as selectively at other rare orphan diseases where we can deploy our capabilities to create value. We do look at both licensing like we did very successfully with the licensing deal with Zymeworks. This brought us obviously Ziihera, and then obviously, for acquisitions like we've done we've been very successfully looking forward to the upcoming PDUFA and then hopefully launched shortly thereafter of Dordaviprone.

因此，即使在支付了約 8.9 億美元的淨價收購 Chimerix 之後，我們仍然處於非常有利的地位，可以繼續投資我們的未來。我們確實關注目前所涉及的各種治療領域，同時也選擇性地關注其他罕見孤兒疾病，我們可以在這些領域運用我們的能力來創造價值。我們確實考慮過這兩種許可，就像我們與 Zymeworks 達成的許可協議非常成功一樣。這顯然為我們帶來了 Ziihera，然後顯然，對於像我們所做的收購，我們非常成功地期待即將到來的 PDUFA，然後希望在那之後不久推出 Dordaviprone。

So we continue to be active in looking at opportunities, see a number of them we think that would make sense for us across our various therapeutic areas, and I would expect to see us continue to be active in this area. I would say on the margin, the uncertainty that's created by some of the tariff and other policy discussions does not change fundamentally what we're looking to do, but probably the margin means that we want to take a slightly more conservative capital structure stance.

因此，我們將繼續積極尋找機會，發現一些我們認為對我們各個治療領域都有意義的機會，我希望看到我們繼續活躍在這個領域。我想說，從邊際上講，一些關稅和其他政策討論所造成的不確定性不會從根本上改變我們想要做的事情，但可能邊際意味著我們希望採取略微更為保守的資本結構立場。

Maybe keeping a bit more cash than we might otherwise and maybe not fully using all of the potential debt capacity that we have, but still able to use a significant portion of that to advance our corporate development efforts. So that gives you some context.

也許我們會保留比平常多一點的現金，也許不會充分利用我們擁有的所有潛在債務能力，但仍然可以使用其中很大的一部分來推進我們的企業發展工作。這為您提供了一些背景資訊。

Ashwani Verma, UBS.

瑞銀的 Ashwani Verma。

Hi. Yeah, thanks for taking my question. I just wanted to clarify, I think you mentioned that one last week of ordering, is that for a handful of [farers] or which part is it for, or is it across the business?

你好。是的，感謝您回答我的問題。我只是想澄清一下，我想您提到了上週的訂購，這是針對少數幾個 [farers] 還是針對哪一部分，還是針對整個企業？

Yes, that would have been across our US oncology business and common for the various products there.

是的，這適用於我們美國的腫瘤學業務，並且適用於那裡的各種產品。

Renee, anything you want to add in?

蕾妮，還有什麼要補充的嗎？

No, that's correct.

不，沒錯。

Mohit Bansal, Wells Fargo.

富國銀行的 Mohit Bansal。

Great, thank you for taking my question. I have a question for you, Rob. So in our conversation with some breast cancer doctors, the interesting takeaway was that it is not a hormone confusion that -- and HER2 would become first-line agent for all the HER2 positive patients. Likely, part of it is safety and comfort with the Cleopatra regimen. So the question is, do you see a potential for Zani to be the first line as well, and what kind of trials you may have to do that because Cleopatra is a really long regimen here?

太好了，謝謝你回答我的問題。我有一個問題想問你，羅布。因此，在我們與一些乳癌醫生的交談中，有趣的是，這並不是荷爾蒙混淆——HER2 將成為所有 HER2 陽性患者的第一線藥物。可能部分原因是克莉奧佩特拉療法的安全性和舒適性。所以問題是，您是否認為 Zani 也有潛力成為第一線藥物，以及由於 Cleopatra 的療程很長，您可能需要進行哪些試驗？

Thank you.

謝謝。

Sure. Well, I mean, I would just reinforce our primary strategy, which is the position after in HER2, because of the data we've generated showing activity of Zani, very promising activity after just about any prior and even multiple different HER2 agents, including standard frontline therapy, which is Herceptin, Perjeta and [Xymo], and HER2 TDM1, (inaudible), et cetera.

當然。嗯，我的意思是，我只想強調我們的主要策略，即 HER2 之後的定位，因為我們生成的數據顯示 Zani 的活性，在幾乎所有先前甚至多種不同的 HER2 藥物之後的非常有希望的活性，包括標準一線療法，即赫賽汀、Perjeta 和 [Xymo]，以及 HER2 TDM1，（聽不清）等等。

So positioning it after in HER2, which is currently second line and likely to move to front line for, I would say, a great majority of patients in this disease setting is really very meaningful, and there won't be any other HER2 therapies that will have been evaluated in that particular setting. Remember, these patients tend to go on to get multiple lines of therapy.

因此，將其定位於 HER2 之後，目前是二線治療，但對於這種疾病環境中的絕大多數患者來說，很可能會轉為一線治療，這確實非常有意義，而且在這種特定環境中不會有任何其他 HER2 療法進行評估。請記住，這些患者往往會接受多種治療。

You're right that there would be a few -- there would be some patients who may not tolerate and HER2 or would have some preexisting condition that would prevent them from -- and I think in those cases, patient who's either progressed on or intolerant in HER2 could move on to Zanidatamab based on the 303 trial. If and HER2 is ultimately approved in the frontline setting, I do think it will be the great majority of patients who get it based on the strong advocacy.

您說得對，確實有少數患者可能無法耐受 HER2，或者存在一些阻礙他們接受治療的先前存在的疾病，我認為在這些情況下，根據 303 試驗的結果，HER2 出現進展或無法耐受的患者可以轉用 Zanidatamab。如果 HER2 最終在前線治療中獲得批准，我確實認為，基於強有力的倡導，絕大多數患者都會接受該療法。

Sean Laaman, Morgan Stanley.

摩根士丹利的肖恩拉曼。

Hi, this is Mike Read on for Sean Lamaan. Thank you for taking our question. For Zywav, in narcolepsy, are you able to provide a more granular breakout for patients in oxybate versus high sodium switches? And then in IH, how are you thinking about Zywav value proposition with potential for a competitive threat there from the [REZ]? Thank you.

大家好，我是 Sean Lamaan 的 Mike Read。感謝您回答我們的問題。對於 Zywav 治療嗜睡症，您是否能夠為接受羥丁酸鹽和高鈉藥物轉換的患者提供更詳細的細分？然後在 IH，您如何看待 Zywav 的價值主張以及由此帶來的競爭威脅？[REZ]？謝謝。

Yeah, so with respect to the narcolepsy adds, we have seen primarily adds in the quarter coming from new to oxybate patients, and I think that does speak to what we're now starting to see, which is a bit of an expansion to the market, given that this is a more mature product. We've been really pleased with what we're seeing in terms of both field execution, the appreciation of low sodium to physicians and also to patients, and that's really resonating.

是的，就嗜睡症而言，我們在本季度主要看到來自新接受羥丁酸鹽治療的患者，我認為這確實說明了我們現在開始看到的情況，考慮到這是一種更成熟的產品，這對市場來說是一種擴展。我們對現場執行情況以及醫生和患者對低鈉飲食的認可感到非常高興，這確實引起了共鳴。

It's clear that HCPs and patients are prioritizing long-term health benefits of low sodium as well as the dosing flexibility that Zywav offers. So we do see switching to or shifting over to IH. We do see IH as the area where there's the most opportunity to drive growth.

很明顯，HCP 和患者優先考慮低鈉的長期健康益處以及 Zywav 提供的劑量靈活性。因此我們確實看到了向 IH 的轉變或轉移。我們確實認為智慧家庭是最具成長機會的領域。

With respect to any future potential competition in IH from Lumryz, I would say again, Zywav is the only low sodium option, and we do know from the data that we have been able to generate we know that narcolepsy and IH patients are at increased risk for cardiovascular comorbidities relative to the general population, and so we do continue to see all high sodium oxybate patients as potential Zywav patients.

對於 Lumryz 在 IH 領域未來可能帶來的競爭，我想再次強調，Zywav 是唯一的低鈉選擇，而且從我們能夠產生的數據中我們確實知道，發作性睡病和 IH 患者相對於一般人群而言，患心血管合併症的風險更高，因此我們確實會繼續將所有高鈉羥基丁酸鹽患者視為潛在的 Zywav 患者。

And keep in mind that within our label for Zywav for idiopathic hypersomnia, there is flexible dosing. That indication is twice nightly or once nightly depending on what the physician and the patients choose to pursue in terms of their therapy. So we feel we're quite well positioned with respect to narcolepsy and idiopathic hypersomnia.

請記住，我們針對特發性嗜睡症的 Zywav 標籤內有靈活的劑量。該指徵是每晚兩次或每晚一次，取決於醫生和患者選擇的治療方法。因此，我們認為我們在發作性睡病和特發性嗜睡症方面處於相當有利的地位。

I will also just jump in and point out that for those of you that saw the court decision today, given that our IP has been found to be valid, that Avadel has admitted to infringing it. We still don't see, even after today's ruling, a viable path for Avadel to commercialize Lumryz an IH before the expiration of the relevant patent in 2036. So I totally agree with everything Renee said in terms of potential competitive positioning and differences between the product, but there's some room to go before we actually do have competition in IH.

我還要指出的是，對於今天看到法院判決的人來說，鑑於我們的智慧財產權被認定為有效，Avadel 已承認侵犯了我們的智慧財產權。即使在今天的裁決之後，我們仍然看不到 Avadel 在 2036 年相關專利到期之前將 Lumryz IH 商業化的可行途徑。因此，我完全同意 Renee 所說的有關潛在競爭定位和產品差異的一切，但在智慧家庭領域真正面臨競爭之前，我們還有一些發展空間。

Gary Nachman, Raymond James.

蓋瑞納赫曼、雷蒙詹姆斯。

Thanks, and good afternoon. So first I hear on BTC, understanding it's a small indication, how is the ramp going, how rapid is the penetration, and what's the anecdotal feedback on how the drug is performing? And have there been any challenges with access and how you're helping facilitate that?

謝謝，下午好。因此，我第一次聽說 BTC，了解到它是一個小跡象，其增長如何，滲透速度有多快，以及關於該藥物表現的軼事反饋是什麼？在訪問方面是否存在任何挑戰？您如何幫助實現這一目標？

And then if GEA ends up being positive in first line as a bigger market, would you consider changes to pricing at all and also how your promotional efforts would change for that indication versus BTC? Thanks.

那麼，如果 GEA 最終在更大的市場中取得積極進展，您是否會考慮改變定價，以及與 BTC 相比，您的促銷力度將如何變化？謝謝。

Yeah, thanks for the question. So we had our first patients treated in December shortly after launch for BTC, and the reception has been quite positive. HCPs are glad to have Ziihera available to treat patients. Just as a reminder, BTC is a very small patient population, 3,000 patients in the US in first line and second line. And therefore, we do expect revenues from the first indication, as we've stated, to be quite modest.

是的，謝謝你的提問。因此，我們在 BTC 推出後不久於 12 月就為第一批患者進行了治療，並且反應非常積極。醫療保健人員很高興能使用 Ziihera 來治療患者。需要提醒的是，BTC 患者群體非常小，美國第一線和第二線治療患者有 3,000 名。因此，正如我們所說的那樣，我們確實預計從第一個跡象來看收入會相當少。

In terms of access, we haven't really had any issues. What we're in the process of doing is ensuring -- we've spent quite a lot of time in these first few months ensuring that we have agreements and the necessary logistics in place for community and academic centers to be able to get access to the product rapidly and certainly the efficacy supporting this approval is something that they're excited to be able to bring to patients.

在訪問方面，我們實際上沒有遇到任何問題。我們正在做的事情是確保——在最初的幾個月裡，我們花費了大量時間來確保我們已達成協議並準備好必要的後勤保障，以便社區和學術中心能夠迅速獲得該產品，而且他們很高興能夠將支持此項批准的功效帶給患者。

When we look at GEA, we're excited to be able to read out that study in the second half with that data and with publication of that data, we would intend to go rapidly towards again trying to get NCCN guidelines in place similar to what we intend to do relative to Zepzelca. Of course, we would not promote without having an approval, but having the product on NCCN guidelines will enable use for that indication should physicians choose to do so.

當我們查看 GEA 時，我們很高興能夠在下半年讀出該研究的數據，並且隨著該數據的發布，我們打算迅速再次嘗試制定 NCCN 指南，類似於我們打算對 Zepzelca 採取的措施。當然，我們不會在沒有獲得批准的情況下進行推廣，但如果醫生選擇將產品納入 NCCN 指南，則可以將其用於該適應症。

I think with respect to pricing, we're in a good position. We typically will comment on pricing when we have a launch slash approval, so stay tuned, but we think given the benefit that we are seeing in efficacy, we'll be in a good position where we are today.

我認為就定價而言，我們處於有利地位。當我們獲得上市批准時，我們通常會對定價發表評論，因此請繼續關注，但我們認為，鑑於我們在功效方面看到的好處，我們今天將處於有利地位。

Charles Duncan, Cantor Fitzgerald.

查爾斯鄧肯、康托菲茨傑拉德。

(technical difficulty) on for Charles, thank you for taking our questions. So you reiterated confidence in Epidiolex reaching blockbuster status in 2025. Can you speak about any catalyst or what market dynamics underpin that expectation? And also, can you talk about any meaning (technical difficulty) in the US or in off-label usage that could contribute to this trajectory? Thank you.

（技術難題）查爾斯，感謝您回答我們的問題。所以您重申了對 Epidiolex 在 2025 年成為重磅藥物的信心。您能談談任何催化劑或支撐這一預期的市場動態嗎？另外，您能否談談在美國或標籤外使用中可能導致這種軌蹟的任何含義（技術難度）？謝謝。

Yeah, I didn't hear the full question, but what I understood was one --

是的，我沒有聽完整個問題，但我理解的是--

I can jump in on the first part, Renee, and just say our confidence that it remains on track for blockbuster status is in part driven by -- it's already at that run rate and has been continuing to grow as you saw with the 10% first quarter of first-quarter growth.

蕾妮，我可以加入第一部分，我只想說，我們對它仍然有望成為一部賣座影片的信心部分源於——它已經達到了這樣的運行率，並且一直在持續增長，正如你在第一季度看到的那樣，它實現了 10% 的增長率。

Renee, you can comment on where growth can be coming from, but we're very solidly on track.

蕾妮，你可以評論一下成長來自哪裡，但我們的步伐非常穩健。

Yeah, thanks, Bruce. The call had cut out for me. So we are quite confident in where we're going with respect to the future. Epidiolex is a highly differentiated product within the ASM landscape. We have a robust body of evidence supporting that both on the seizure side as well as the non-seizure benefits, and that data continues to resonate with physicians and caregivers, in particular on the non-seizure benefit side, cognition, behavior, emotional and social function, and also the broad spectrum efficacy and well-characterized safety profile enables physicians to have epi dialects combined well with other agents, which is particularly important in this area given polypharmacy.

是的，謝謝，布魯斯。我的通話已經中斷。因此，我們對未來的發展方向充滿信心。Epidiolex 是 ASM 領域內高度差異化的產品。我們有大量證據支持該藥物在癲癇發作和非癲癇發作方面的益處，並且這些數據繼續引起醫生和護理人員的共鳴，特別是在非癲癇發作益處方面，認知、行為、情緒和社會功能，而且廣譜療效和明確的安全性特徵使醫生能夠將流行病學方言與其他藥物很好地結合起來，這在多重用藥的領域尤為重要。

While we do not promote off label, we do see the product used across a number of different epilepsy subtypes across the underlying seizures for which we've shown efficacy. And then in terms of additional growth, we're having great momentum in the adult and long-term care setting. We have a new screening tool that we've put into -- that we've launched an additional initiative to help identify LGS, for example, in previously undiagnosed patients in the adult setting. Our access has been high quality and continues to improve.

雖然我們不推廣非說明書用途的產品，​​但我們確實看到該產品用於治療多種不同類型的癲癇亞型，並且已經證明對各種類型的癲癇有療效。就額外成長而言，我們在成人和長期照護領域有著巨大的發展動能。我們引入了一種新的篩檢工具——我們推出了一項額外的措施來幫助識別 LGS，例如，在成人環境中識別以前未確診的患者。我們的訪問品質一直很高並且還在不斷提高。

And then also with respect to our nurse navigator program, we're seeing strong persistency and seeing that even become stronger with respect to the nurse navigator program helping to guide patients through starting therapy. So all of those elements give us confidence in the overall growth and of course, the durability we've talked about having settled with our ANDA filers, we think we're in an excellent position there as well.

然後，就我們的護理人員導航計劃而言，我們看到了強大的持久性，並且看到護理人員導航計劃在幫助指導患者開始治療方面變得更加強大。因此，所有這些因素都讓我們對整體成長充滿信心，當然，我們談到的與 ANDA 文件提交者達成的持久性，我們認為我們在這方面也處於有利地位。

Joon Lee, Truist Securities.

Joon Lee，Truist Securities。

Hey, thanks for squeezing me in. For the HERIZON-GEA, are you able to comment on the ratio of patients who are PD1 positive? I mean, is the ratio closer to what we saw in KEYNOTE-811 or closer to your Phase 1/2 [Zeno] plus chemo plus study?

嘿，謝謝你擠我進來。對於 HERIZON-GEA，您能否評論一下 PD1 陽性患者的比例？我的意思是，這個比例是否更接近我們在 KEYNOTE-811 中看到的比例，或者更接近您的第 1/2 階段 [Zeno] 加化療加研究的比例？

Thank you.

謝謝。

I don't have that information, and I just would remind you that how you characterize positive depends a little bit on which assay you're using, et cetera. So we are measuring it and we'll have the ability to look at that, post hoc as needed to support regulatory approval.

我沒有這方面的信息，我只是想提醒你，如何表徵陽性有點取決於你使用的分析方法等等。因此，我們正在對其進行測量，並且我們將有能力對其進行事後審查，以支持監管部門的批准。

That will conclude our question-and-answer session, and I will now turn the call back over to Chairman and Chief Executive Officer, Bruce Cozadd, for closing remarks.

我們的問答環節到此結束，現在我將把電話轉回給董事長兼首席執行官布魯斯·科扎德 (Bruce Cozadd) 作結束語。

Thank you, operator. Let me just say with Epidiolex and Zywav growth, some upcoming exciting approvals on the oncology side of our business across three different products and GEA data upcoming. There's a lot to look forward to.

謝謝您，接線生。我只想說，隨著 Epidiolex 和 Zywav 的成長，我們業務的腫瘤學方面即將獲得三種不同產品的令人興奮的批准，而 GEA 數據也即將發布。有很多事情值得期待。

I'd just like to close today's call by recognizing our Jazz colleagues for their efforts and thanking our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

在今天的電話會議結束時，我想感謝我們的 Jazz 同事所做的努力，並感謝我們的合作夥伴和股東的持續信任和支持。感謝大家今天的參與。

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝大家的加入。您現在可以斷開連線。