Jazz Pharmaceuticals PLC (JAZZ) 2023 Q2 法說會逐字稿

Good afternoon, and thank you for attending the Jazz Pharmaceuticals Second Quarter 2023 Financial Results Call. My name is Elissa, and I will be your moderator for today's call. (Operator Instructions)

下午好，感謝您參加 Jazz Pharmaceuticals 2023 年第二季度財務業績電話會議。我叫艾麗莎，我將擔任今天電話會議的主持人。 （操作員說明）

I would now like to pass the call over to the Jazz Pharmaceuticals team. You may proceed.

我現在想將電話轉給 Jazz Pharmaceuticals 團隊。您可以繼續。

Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its second quarter 2023 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, Executive Vice President and Chief Financial Officer; Dan Swisher, President and Chief Operating Officer; and Rob Iannone, Executive Vice President, Global Head of R&D; Kim Sablich, Executive Vice President and General Manager of United States, will join the team for Q&A.

謝謝接線員，大家下午好。今天，Jazz Pharmaceuticals 公佈了 2023 年第二季度財務業績。本網絡廣播附帶的幻燈片演示文稿可在我們網站的投資者部分獲取。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首席執行官 Bruce Cozadd； Renee Gala，執行副總裁兼首席財務官；丹·斯威舍 (Dan Swisher)，總裁兼首席運營官； Rob Iannone，執行副總裁兼全球研發主管；美國執行副總裁兼總經理 Kim Sablich 將加入團隊進行問答。

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 these forward-looking statements.

在幻燈片2 上，我想提醒您，今天的網絡廣播包含前瞻性陳述，例如與我們未來的財務和運營業績、增長潛力以及預期開發和商業化里程碑和目標相關的陳述，其中涉及可能存在的風險和不確定性。導致實際事件、業績和結果與這些前瞻性陳述中包含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 in our latest SEC disclosure documents, 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.

我們鼓勵您查看今天的新聞稿、幻燈片和最新的SEC 披露文件中包含的聲明，其中確定了可能導致公司的實際事件、業績和結果與前瞻性陳述中包含的內容存在重大差異的某些因素。查看今天網絡廣播中的聲明。我們不承擔更新前瞻性陳述的責任或義務。

Turning to Slide 3. On this webcast, we'll discuss non-GAAP financial measures. Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available on the Investors section of our website. I'll now turn the call over to Bruce.

轉向幻燈片 3。在本次網絡廣播中，我們將討論非 GAAP 財務指標。這些非 GAAP 財務指標的描述以及 GAAP 與非 GAAP 財務指標的調節包含在今天的新聞稿和我們網站投資者部分的幻燈片演示中。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. In the second quarter of 2023, we once again delivered strong commercial results, advanced our efforts to unlock the tremendous potential of our pipeline, and built on our record of driving operational excellence. In particular, our results in the second quarter highlight the durability and growth potential of our commercial portfolio, the capabilities and productivity of our R&D efforts and our focus on operational excellence.

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。2023 年第二季度，我們再次取得了強勁的商業成果，進一步努力釋放了管道的巨大潛力，並建立了推動卓越運營的記錄。特別是，我們第二季度的業績凸顯了我們商業產品組合的耐用性和增長潛力、我們研發工作的能力和生產力以及我們對卓越運營的關注。

We are pleased to report strong execution across our commercial portfolio with all 3 key growth drivers of our commercial business, Xywav, Epidiolex and Rylaze achieving year-over-year double-digit growth. Xywav grew by 39% in the second quarter compared to the same period last year and is annualizing at well over $1 billion in revenue. Xywav continues to be the oxybate of choice and the only approved therapy for idiopathic hypersomnia. We expect our oxybate franchise to contribute $2 billion of the $5 billion in total revenue component of Vision 2025 and are well positioned to reach this target.

我們很高興地報告我們的商業產品組合的強勁執行力，我們商業業務的所有 3 個關鍵增長驅動因素 Xywav、Epidiolex 和 Rylaze 均實現了同比兩位數增長。 Xywav 第二季度與去年同期相比增長了 39%，年收入遠超 10 億美元。 Xywav 仍然是首選的羥丁酸鹽，也是唯一批准治療特發性睡眠過度的療法。我們預計我們的羥丁酸特許經營權將貢獻 2025 年願景 50 億美元總收入中的 20 億美元，並且有能力實現這一目標。

As a reminder, our 2023 neuroscience revenue guidance, which we are raising at the midpoint today and Vision 2025, both account for the availability of high-sodium oxybate authorized generics or AGs and branded fixed-dose high-sodium oxybate.

提醒一下，我們今天中點提出的 2023 年神經科學收入指導和 2025 年願景都考慮了高羥丁酸鈉授權仿製藥或 AG 和品牌固定劑量高羥丁酸鈉的可用性。

Epidiolex growth remains strong, and we are confident in its potential to reach blockbuster status. We achieved double-digit net sales growth in 2Q '23 compared to the same period last year as we continued to drive prescriber growth across our global markets. Our launch in Europe is gaining momentum, with additional international launches and indication expansions expected this year. In oncology, Rylaze has continued to grow in the U.S., underpinned by strong demand and our increasing emphasis on the adolescent and young adult market.

Epidiolex 的增長依然強勁，我們對其達到重磅炸彈地位的潛力充滿信心。與去年同期相比，我們在 2023 年第二季度實現了兩位數的淨銷售額增長，因為我們繼續推動全球市場的處方者增長。我們在歐洲的上市勢頭正在增強，預計今年將有更多的國際上市和適應症擴展。在腫瘤學領域，在強勁需求以及我們對青少年和年輕人市場日益重視的支撐下，Rylaze 在美國持續增長。

Moving to our pipeline. Given the level of productivity in our R&D organization, I'm going to call out just a few items. Rob will cover our R&D progress in more detail later in the call. Our pipeline continues to advance towards meaningful catalysts with the potential for as many as 4 late-stage data readouts through 2024, the first being JZP150 late this year, followed by suvecaltamide and Zanidatamab in GEA next year and top line PFS for Zepzelca in combination with Tecentriq, in first-line extensive-stage small cell lung cancer at the end of 2024 or early 2025.

轉向我們的管道。考慮到我們研發組織的生產力水平，我將僅列出幾項。 Rob 將在稍後的電話會議中更詳細地介紹我們的研發進展。我們的管道繼續向有意義的催化劑邁進，有可能在2024 年之前進行多達4 個後期數據讀出，第一個是今年年底的JZP150，其次是明年GEA 的舒維卡胺和Zanidatamab，以及Zepzelca的頂線PFS Tecentriq，將於 2024 年底或 2025 年初用於一線廣泛期小細胞肺癌。

In addition to its strong commercial performance in the U.S., we are extremely pleased that we recently received a positive CHMP opinion on our marketing authorization application for JZP-458 marketed as Rylaze in the U.S. and expect European Commission approval later this year. Since we added Zanidatamab to our pipeline last year, it has continued to impress, and we're excited by its broad applicability, which we believe represents $2 billion-plus in peak sales potential. Positive pivotal data from our Phase IIb trial in biliary tract cancers or BTC, were featured in an oral session at this year's ASCO conference and concurrently published in The Lancet Oncology.

除了在美國強勁的商業表現外，我們非常高興的是，我們最近收到了CHMP 對我們在美國以Rylaze 名義銷售的JZP-458 的營銷授權申請的積極意見，並預計歐盟委員會將在今年晚些時候獲得批准。自從我們去年將 Zanidatamab 添加到我們的產品線以來，它繼續給人留下了深刻的印象，我們對其廣泛的適用性感到興奮，我們相信這代表著 20 億美元以上的峰值銷售潛力。我們的膽道癌或 BTC IIb 期試驗的積極關鍵數據在今年的 ASCO 會議的口頭會議上得到了專題報導，並同時發表在《柳葉刀腫瘤學》上。

These data were also selected for the best of ASCO meeting. Top line data readout from the ongoing Phase III gastroesophageal adenocarcinoma or GEA trial is expected in 2024. I'm also pleased to report that we recently received IND clearance for JZP898, an engineered interferon alpha cytokine prodrug that is activated specifically within the tumor micro environment where it can stimulate interferon alpha receptors on cancer-fighting immune effector cells. With this milestone achieved, we remain on track to initiate a Phase I trial of JZP898 later this year.

這些數據也被ASCO會議評選為最佳數據。正在進行的III 期胃食管腺癌或GEA 試驗的主要數據預計將於2024 年讀出。我還很高興地報告，我們最近獲得了JZP898 的IND 許可，這是一種工程干擾素α 細胞因子前藥，在腫瘤微環境中特異性激活它可以刺激抗癌免疫效應細胞上的干擾素α受體。隨著這一里程碑的實現，我們仍有望在今年晚些時候啟動 JZP898 的 I 期試驗。

On the operational side, we generated continued top and bottom line growth in the second quarter. Our commercial execution, coupled with our focus on operational excellence has put us in a strong financial position enabling us to execute a focused capital allocation strategy to invest in the products, pipeline programs and corporate development opportunities with the highest potential to deliver sustainable growth and enhanced value.

在運營方面，我們在第二季度實現了收入和利潤的持續增長。我們的商業執行力，加上我們對卓越運營的關注，使我們擁有強大的財務狀況，使我們能夠執行有針對性的資本配置戰略，投資於最有潛力實現可持續增長和增強的產品、管道項目和企業發展機會。價值。

Given our financial strength and our current stock price, we have resumed share repurchases under our existing program, which Renee will expand upon shortly. Based on our performance in the first half of 2023 and expectations for the remainder of the year, we are raising our full year financial guidance for 2023. And longer term, we believe we are well positioned to achieve Vision 2025. Renee will provide additional commentary on our financials and guidance later in the call.

鑑於我們的財務實力和當前的股價，我們已根據現有計劃恢復了股票回購，Renee 將很快擴大該計劃。根據我們 2023 年上半年的業績和對今年剩餘時間的預期，我們正在提高 2023 年全年財務指引。從長遠來看，我們相信我們有能力實現 2025 年願景。Renee 將提供更多評論稍後在電話會議中介紹我們的財務狀況和指導。

Turning to Slide 6. We are excited about the progress we've achieved in the second quarter and believe it has substantially advanced us in all 3 areas of Vision 2025, and we are well positioned to achieve these important milestones in our transformation to a high-growth global biopharma leader.

轉向幻燈片6。我們對第二季度取得的進展感到興奮，並相信它使我們在2025 年願景的所有3 個領域取得了實質性進展，並且我們已做好充分準備，在向高水平轉型的過程中實現這些重要里程碑。 -成長為全球生物製藥領導者。

I'll now turn the call over to Dan to review our commercial performance, after which Rob will share an update on our R&D progress, Renee will provide a financial overview, and then we'll open the call to Q&A. Dan?

我現在將把電話轉給 Dan 來審查我們的商業表現，之後 Rob 將分享我們研發進展的最新信息，Renee 將提供財務概覽，然後我們將開始電話問答。擔？

Thanks, Bruce. I'm excited to provide an update on our commercial progress. Starting on Slide 8, with neuroscience and oxybate, we remain confident in the strength and durability of our oxybate franchise as Xywav continues to be the oxybate of choice and the only approved therapy for IH. Xywav revenues were $327 million for the second quarter of 2023 representing growth of 39% compared to the same period in 2022. I'll note, this growth was against the backdrop of high-sodium oxybate competition entering the market in January of this year.

謝謝，布魯斯。我很高興能夠提供有關我們商業進展的最新信息。從幻燈片8 開始，從神經科學和羥丁酸鹽開始，我們對我們的羥丁酸鹽系列產品的強度和耐用性仍然充滿信心，因為Xywav 仍然是首選的羥丁酸鹽和唯一獲批的IH 療法。 Xywav 2023 年第二季度的收入為3.27 億美元，與2022 年同期相比增長了39%。我要指出的是，這一增長是在今年1 月高羥丁酸鈉競爭進入市場的背景下實現的。

In narcolepsy, our focus remains on educating patients and prescribers on the benefits of reducing sodium intake and this message continues to resonate. In addition to health benefits of liver sodium, based on our discussions with health care professionals and experienced oxybate patients dosing flexibility is a valued attribute of Xywav. Exiting the second quarter, approximately 9,300 narcolepsy patients were taking Xywav, and Xywav continues to be the oxybate of choice in the marketplace.

在發作性睡病方面，我們的重點仍然是教育患者和處方醫生減少鈉攝入量的好處，並且這一信息繼續引起共鳴。除了肝鈉對健康的益處外，根據我們與醫療保健專業人員和經驗豐富的羥丁酸鹽患者的討論，劑量靈活性是 Xywav 的一個重要屬性。截至第二季度，約有 9,300 名發作性睡病患者正在服用 Xywav，Xywav 仍然是市場上首選的羥丁酸鹽。

In IH, we see continued growth of new prescribers with approximately 2,200 active patients taking Xywav for treatment of IH exiting the second quarter. IH is a 24-hour sleep disorder. Despite sleeping a normal or longer than normal amount of time each night people with IH may still experience debilitating symptoms during the day. Xywav is the first and only treatment approved by FDA to treat the full condition of IH. We are focused on educating prescribers on the importance of proper diagnosis and identifying appropriate patients who can benefit from Xywav therapy. And a survey of sleep specialists indicated that 70% anticipate increasing their prescribing in the next 6 months.

在 IH 方面，我們看到新處方者持續增長，第二季度約有 2,200 名活躍患者服用 Xywav 治療 IH。 IH 是一種 24 小時睡眠障礙。儘管 IH 患者每晚睡眠時間正常或長於正常時間，但白天仍可能出現虛弱症狀。 Xywav 是 FDA 批准的第一個也是唯一一個治療 IH 全部病症的治療方法。我們致力於教育處方者正確診斷的重要性，並確定可以從 Xywav 治療中受益的合適患者。對睡眠專家的一項調查表明，70% 的人預計在未來 6 個月內增加他們的處方。

With regard to the average number of patients on Xywav exiting the quarter, there was an operational change in our specialty pharmacy, which caused delays in getting refills on time for some Xywav patients. This is being addressed and importantly, overall second quarter Xywav HCPs and patient demand were in line with our expectations in prior quarters. As Renee will review in more detail, we have raised our neuroscience revenue guidance at the midpoint reflecting our continued confidence in the growth opportunity for Xywav wave and the durability of oxybate.

就本季度退出 Xywav 的患者平均人數而言，我們的專業藥房發生了運營變化，導致一些 Xywav 患者按時補充藥物的情況出現延誤。這個問題正在得到解決，重要的是，第二季度總體 Xywav HCP 和患者需求符合我們前幾個季度的預期。正如 Renee 將更詳細地回顧的那樣，我們在中點上調了神經科學收入指引，反映出我們對 Xywav Wave 的增長機會和 oxybate 的耐久性的持續信心。

Total revenues for the combined oxybate business, including royalties from a high-sodium oxybate AG decreased 2% to $492 million in the second quarter compared to the same period in 2022. There were approximately 16,200 total average active Jazz oxybate patients in the second quarter, a decrease compared to the end of the first quarter, primarily reflecting the expected impact of Xyrem as a result of the availability of a high-sodium oxybate AG. Our focus is on continuing to grow low-sodium Xywav across both narcolepsy and IH, and we are pleased with Xywav's growth across both indications even as additional high-sodium oxybate competition is available for patients with narcolepsy.

與2022 年同期相比，第二季度合併後的oxybate 業務總收入（包括高鈉oxybate AG 的特許權使用費）下降了2%，至4.92 億美元。第二季度平均活躍Jazz oxybate 患者總數約為16,200 名，與第一季度末相比有所下降，主要反映了 Xyrem 由於高鈉羥丁酸 AG 的可用性而產生的預期影響。我們的重點是繼續開發針對嗜睡症和 IH 的低鈉 Xywav，我們對 Xywav 在這兩個適應症上的增長感到滿意，儘管嗜睡症患者可以獲得額外的高鈉羥丁酸鹽競爭。

The continued growth of Xywav is one of the factors that contributed to our increased 2023 neuroscience revenue guidance. And as Bruce mentioned, we are well positioned to achieve our Vision 2025 target of $2 billion in revenue from our oxybate franchise.

Xywav 的持續增長是我們提高 2023 年神經科學收入指引的因素之一。正如 Bruce 提到的，我們完全有能力實現 2025 年願景目標，即從我們的 oxybate 特許經營中獲得 20 億美元的收入。

Slide 9 highlights the compelling low-sodium health benefits we are sharing with health care professionals and patients. As narcolepsy is a debilitating chronic condition, we have focused on educational efforts around the lifelong burden of high sodium intake for narcolepsy patients who live with a 2 to 3x higher risk than the general population of cardiovascular comorbidities such as stroke and heart failure.

幻燈片 9 重點介紹了我們與醫療保健專業人員和患者分享的令人信服的低鈉健康益處。由於發作性睡病是一種使人衰弱的慢性疾病，因此我們重點關注發作性睡病患者終生高鈉攝入負擔的教育工作，這些患者患中風和心力衰竭等心血管合併症的風險比一般人群高2 至3 倍。

Xywav is the only approved low-sodium oxybate and the only oxybate without a labeled warning about high sodium intake that has 92% less sodium than high-sodium oxybates. The American Heart Association recommends a maximum of 1,500 milligrams of sodium per day. While high-sodium AGs and branded oxybates have 1,100 to 1,640 milligrams of sodium, Xywav has only 100 to 140 milligrams, a reduction of 1,000 to 1,500 milligrams of sodium per day. To put this in perspective, it would take 12 years of treatment with Xywav to equal the sodium intake of 1 year of high-sodium oxybate treatment. This has significant potential health benefits, including lower blood pressure and improved cardiovascular health.

Xywav 是唯一獲得批准的低鈉羥丁酸鹽，也是唯一沒有關於高鈉攝入量標籤警告的羥丁酸鹽，其鈉含量比高鈉羥丁酸鹽少 92%。美國心臟協會建議每天最多攝入 1,500 毫克鈉。高鈉 AG 和品牌羥丁酸鹽含有 1,100 至 1,640 毫克鈉，而 Xywav 僅含有 100 至 140 毫克，每天減少 1,000 至 1,500 毫克鈉。從長遠來看，Xywav 治療需要 12 年才能達到高羥丁酸鈉治療 1 年的鈉攝入量。這具有顯著的潛在健康益處，包括降低血壓和改善心血管健康。

To add to the literature on sodium impact, we presented data at this year's American Academy of Neurology Meeting that showed narcolepsy patients treated with high-sodium oxybate had a higher risk of new onset hypertension diagnosis or anti-hypertensive medication initiation within 180 days of starting therapy when compared to a matched control group of narcolepsy patients not being treated with high-sodium oxybate. In fact, the risk of those taking high-sodium oxybate was approximately twice that of the control group. We believe these data highlight that sodium intake is a health concern for all narcolepsy patients and one that can have near-term consequences.

為了補充有關鈉影響的文獻，我們在今年的美國神經病學學會會議上提供的數據顯示，接受高羥丁酸鈉治療的發作性睡病患者在開始治療後180 天內診斷出新發高血壓或開始服用抗高血壓藥物的風險較高與未接受高羥丁酸鈉治療的發作性睡病患者的匹配對照組進行比較。事實上，服用高羥丁酸鈉的人的風險大約是對照組的兩倍。我們相信這些數據強調鈉攝入量是所有發作性睡病患者的一個健康問題，並且可能產生短期後果。

FDA has recognized that the difference in sodium content between Xywav and high-sodium oxybate, including Xyrem, AG Xyrem and LUMRYZ is likely to be clinically meaningful in all patients with narcolepsy and that Xywav is safer in all such patients. LUMRYZ is a recently launched branded fixed-dose high-sodium oxybate that has the same sodium content as Xyrem. We believe that the majority of patients and health care providers will continue to prioritize long-term health when evaluating oxybate therapy.

FDA 已經認識到，Xywav 和高羥丁酸鈉（包括 Xyrem、AG Xyrem 和 LUMRYZ）之間鈉含量的差異可能對所有發作性睡病患者俱有臨床意義，並且 Xywav 對所有此類患者更安全。 LUMRYZ 是最近推出的品牌固定劑量高羥丁酸鈉，其鈉含量與 Xyrem 相同。我們相信，大多數患者和醫療保健提供者在評估羥丁療法時將繼續優先考慮長期健康。

With respect to competition from high sodium oxybate authorized generics or AGs, Amneal announced the launch of their AG in early July. Two additional companies, Lupin and Par also have rights to launch AG products. At this time, Par and Lupin have elected not to launch. These 3 AG suppliers are each restricted to a low single-digit percentage of Xyrem sales volume. As a reminder, earlier this year, Hikma launched the volume unlimited AG. Jazz receives meaningful royalties on all high-sodium oxybate AGs.

針對高羥丁酸鈉授權仿製藥或 AG 的競爭，Amneal 於 7 月初宣布推出其 AG。另外兩家公司 Lupin 和 Par 也有權推出 AG 產品。此時，Par 和 Lupin 選擇不發射。這 3 家 AG 供應商各自在 Xyrem 銷量中所佔的百分比都被限制在較低的個位數百分比。提醒一下，今年早些時候，Hikma 推出了容量無限的 AG。 Jazz 從所有高羥丁酸鈉 AG 中獲得了可觀的特許權使用費。

Moving to Slide 10. We remain confident in the blockbuster potential of Epidiolex with yet another quarter of double-digit year-over-year revenue growth. Net product sales increased 15% to $202 million in the second quarter compared to the same period in 2022, driven by underlying demand. We have seen increased penetration in the long-term care setting, driven by additional in-person engagement with physicians, and we have additional opportunities for growth.

轉到幻燈片 10。我們對 Epidiolex 的巨大潛力仍然充滿信心，因為收入將再次實現兩位數的同比增長。在潛在需求的推動下，第二季度產品淨銷售額較 2022 年同期增長 15%，達到 2.02 億美元。在與醫生更多的面對面接觸的推動下，我們看到長期護理環境的滲透率有所提高，並且我們有更多的增長機會。

Turning to Slide 11. We are focused on multiple opportunities to drive Epidiolex to blockbuster status. We continue to see a positive impact from our educational efforts focused on optimal dosing and caregiver reported outcomes beyond seizure control from the BECOME survey, which further differentiates Epidiolex from other antiseizure medicines. In particular, reports from the field indicates that the BECOME data has been very impactful with both HCPs and caregivers.

轉向幻燈片 11。我們專注於將 Epidiolex 推向重磅炸彈地位的多種機會。我們繼續看到我們的教育工作產生了積極影響，重點是最佳劑量，並且護理人員報告的結果超出了 BECOME 調查中癲癇發作控制的範圍，這進一步將 Epidiolex 與其他抗癲癇藥物區分開來。特別是，來自現場的報告表明，BECOME 數據對 HCP 和護理人員都產生了非常大的影響。

The compelling clinical data regarding the use of Epidiolex in combination with Clobazam versus using the agents individually continues to resonate. Our commercial team also has an enhanced focus on further penetration into the adult setting. We are also pleased that our commercialization efforts outside the U.S. continue to gain momentum.

關於 Epidiolex 與 Clobazam 聯合使用與單獨使用這些藥物的令人信服的臨床數據繼續引起共鳴。我們的商業團隊還更加註重進一步滲透到成人環境中。我們還很高興我們在美國以外的商業化努力繼續獲得動力。

Slide 12 illustrates our progress in expanding Epidiolex outside of the U.S. Epidiolex is now launched and reimbursed in 23 countries around the world, including all 5 key European markets. While it's early, we are very encouraged by initial uptake in these markets with favorable pricing and access. We anticipate additional reimbursement decisions and submissions through this year and next.

幻燈片 12 展示了我們在美國以外地區拓展 Epidiolex 的進展。Epidiolex 現已在全球 23 個國家推出並報銷，其中包括所有 5 個主要歐洲市場。雖然現在還為時過早，但我們對這些市場的初步採用以及優惠的價格和准入感到非常鼓舞。我們預計今年和明年還會有更多的報銷決定和提交。

Moving to our oncology franchise beginning on Slide 13. Net product sales for Rylaze were $102 million for the second quarter, a 39% increase year-over-year in our fourth consecutive quarter of growth. We continue to see strong demand for Rylaze, reflecting the significant unmet patient need for a high-quality, reliable supply of erwinia asparaginase for patients with acute lymphoblastic leukemia. Based on the availability of Rylaze, health care professionals have indicated they are returning the best clinical practice in switching therapy at the first signs of hypersensitivity.

從幻燈片 13 開始轉向我們的腫瘤學特許經營業務。第二季度 Rylaze 的淨產品銷售額為 1.02 億美元，同比增長 39%，這是我們連續第四個季度的增長。我們繼續看到對 Rylaze 的強勁需求，反映出急性淋巴細胞白血病患者對高質量、可靠的歐文氏菌天冬酰胺酶供應的巨大需求尚未得到滿足。基於 Rylaze 的可用性，醫療保健專業人員表示，他們正在恢復最佳臨床實踐，在出現過敏症的最初跡象時轉換治療。

We continue to receive positive feedback from health care providers about the adoption of the Monday, Wednesday, Friday dosing regimen, which allows a dosing schedule that is more in line with preferred clinical practice. Rylaze has been almost universally adopted in pediatric oncology protocols, and we are encouraged to see that there is increasing use of Rylaze in the treatment of adolescents in young adults or the AYA market, which is an area of increased emphasis for us in 2023.

我們繼續收到醫療保健提供者關於採用周一、週三、週五給藥方案的積極反饋，該方案允許更符合首選臨床實踐的給藥方案。 Rylaze 已在兒科腫瘤治療方案中幾乎得到普遍採用，我們很高興看到 Rylaze 在青壯年或 AYA 市場的青少年治療中的使用越來越多，這是我們在 2023 年更加重視的領域。

Outside of the U.S., we recently received a positive CHMP opinion. With the positive opinion granted, we anticipate EC approval of our MAA submission later this year. Regarding the market opportunity, I'll note that there is competition in many European markets. Jazz has consistently delivered a reliable, high-quality supply of this important therapy in the U.S., and we are excited for patients and health care providers in Europe to have the opportunity to complete their full course of asparaginase therapy.

在美國之外，我們最近收到了 CHMP 的積極意見。獲得積極意見後，我們預計 EC 將在今年晚些時候批准我們提交的 MAA。關於市場機會，我要指出的是，許多歐洲市場都存在競爭。 Jazz 始終如一地在美國提供這種重要療法的可靠、高質量供應，我們很高興歐洲的患者和醫療保健提供者有機會完成天冬酰胺酶治療的整個療程。

Turning to Slide 14. We rapidly established Zepzelca as a treatment of choice in second-line small cell lung cancer. Net product sales increased 3% to $70 million in the second quarter compared to the same period in 2022. We have achieved significant penetration in the second line setting, but there remains significant unmet need for patients diagnosed with small cell lung cancer with 5-year overall survival rates of less than 10% and median overall survival of 6 to 24 months depending on the stage of diagnosis.

轉向幻燈片 14。我們迅速將 Zepzelca 確立為二線小細胞肺癌的首選治療方法。與2022 年同期相比，第二季度的產品淨銷售額增長了3%，達到7000 萬美元。我們在二線治療中取得了顯著的滲透率，但對於診斷為小細胞肺癌5 年期患者的需求仍然未得到滿足總生存率低於 10%，中位總生存期為 6 至 24 個月，具體取決於診斷階段。

Given this prognosis, there is a further opportunity to both improve patient lives and drive growth through our pivotal Phase III trial in first-line small cell lung cancer in combination with Tecentriq. We expect top line PFS data readout at the end of 2024 or early 2025. In the U.S., there are approximately 27,000 first-line small cell lung cancer patients treated annually. Zepzelca has the potential to increase the duration of response with these earlier-stage patients.

鑑於這種預後，通過我們與 Tecentriq 聯合治療一線小細胞肺癌的關鍵 III 期試驗，還有進一步改善患者生活並推動增長的機會。我們預計一線 PFS 數據將於 2024 年底或 2025 年初公佈。在美國，每年約有 27,000 名一線小細胞肺癌患者接受治療。 Zepzelca 有可能延長這些早期患者的反應持續時間。

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

這樣，我會將其交給 Rob，以獲取有關我們的管道和即將到來的里程碑的最新信息。搶？

Thanks, Dan. Starting on Slide 16. We provided an overview of the key clinical programs in our diversified pipeline. We are excited about the advances we've made so far this year. with the potential for as many as 4 late-stage data readouts through 2023 and 2024, which include JZP150 in PTSD, suvecaltamide in essential tremor, Zanidatamab in GEA and Zepzelca in combination with Tecentriq in first-line small cell lung cancer. I'll discuss a few of our programs in more detail shortly, but I wanted to broadly highlight our progress across the pipeline before moving on.

謝謝，丹。從幻燈片 16 開始。我們概述了我們多元化管道中的關鍵臨床項目。我們對今年迄今為止所取得的進展感到興奮。到 2023 年和 2024 年，有可能獲得多達 4 個後期數據，其中包括治療 PTSD 的 JZP150、治療特發性震顫的舒維卡胺、GEA 的 Zanidatamab 以及一線小細胞肺癌的 Zepzelca 與 Tecentriq 聯合治療。我將很快更詳細地討論我們的一些計劃，但我想在繼續之前廣泛強調我們在整個管道中的進展。

Starting with neuroscience. We expect top line data from our Phase II trial of JZP150 in PTSD by the end of the year. For JZP441, our Orexin-2 receptor agonist that has the potential to treat narcolepsy, IH and other sleep disorders, we anticipate initial proof of concept in healthy volunteers later this year. In addition, we have ongoing trials for suvecaltamide in both essential tremor or ET and Parkinson's disease tremor, with top line data from the ET trial expected in the first half of 2024.

從神經科學開始。我們預計 JZP150 治療 PTSD 的 II 期試驗將在今年年底獲得頂線數據。我們的 Orexin-2 受體激動劑 JZP441 有可能治療嗜睡症、間歇性睡病和其他睡眠障礙，我們預計今年晚些時候將在健康志願者中進行初步概念驗證。此外，我們正在進行舒維卡胺治療特發性震顫或 ET 和帕金森病震顫的試驗，預計 ET 試驗的主要數據將於 2024 年上半年公佈。

Moving to oncology. Zanidatamab is a priority program for us. We aim to advance Zanidatamab to the market as rapidly as possible with second-line BPC representing our first potential commercial indication. We are planning for a potential accelerated approval of Zanidatamab in second-line BTC and have aligned it with the FDA on a confirmatory trial in first-line metastatic BTC where there remains unmet patient needs. We are also evaluating Zanidatamab in GEA, breast cancer and other HER2-positive solid tumors.

轉向腫瘤學。 Zanidatamab 是我們的優先項目。我們的目標是盡快將 Zanidatamab 推向市場，二線 BPC 代表我們的第一個潛在商業適應症。我們正計劃加速批准 Zanidatamab 用於二線 BTC，並已與 FDA 就一線轉移性 BTC 的驗證性試驗進行協調，該試驗尚未滿足患者的需求。我們還在評估 Zanidatamab 在 GEA、乳腺癌和其他 HER2 陽性實體瘤中的作用。

For Zepzelca, we expect top line PFS data readout at the end of 2024 or early 2025. Small cell lung cancer patients have particularly poor outcomes, with a 5-year overall survival rate of less than 10%. Currently, Zepzelca's indicated to treat patients in the second-line setting, but we see a clear mechanistic rationale for Zepzelca to potentially benefit more patients and increase the duration of response in the first-line setting as maintenance therapy in combination with the standard of care.

對於 Zepzelca，我們預計在 2024 年底或 2025 年初公佈一線 PFS 數據。小細胞肺癌患者的預後特別差，5 年總生存率低於 10%。目前，Zepzelca 被指定用於治療二線患者，但我們看到了 Zepzelca 的明確機制原理，作為維持治療與標準護理相結合，它可能使更多患者受益，並延長一線環境中的反應持續時間。

Beyond small cell lung cancer, we have elected to close our Phase II basket trial based on limited responses in 3 solid tumor cohorts. We're analyzing the findings from that trial and continue to explore additional tumor types that may benefit from treatment with Zepzelca.

除了小細胞肺癌之外，基於 3 個實體瘤隊列的有限反應，我們選擇結束 II 期籃子試驗。我們正在分析該試驗的結果，並繼續探索可能受益於 Zepzelca 治療的其他腫瘤類型。

As Dan and Bruce mentioned earlier, we are very pleased to have received a positive CHMP opinion on JZP458, which is marketed as Rylaze in the U.S. with Monday, Wednesday, Friday, at every 48-hour dosing regimens, as well as IV and IM administration. We anticipate EC approval later this year.

正如 Dan 和 Bruce 之前提到的，我們很高興收到 CHMP 對 JZP458 的積極意見，JZP458 在美國以 Rylaze 為商品名，週一、週三、週五每 48 小時給藥方案以及 IV 和 IM 給藥方案行政。我們預計 EC 將在今年晚些時候獲得批准。

Moving to Slide 17. I'll expand on my earlier comments regarding Zanidatamab. Zanidatamab is a novel bispecific antibody that can simultaneously bind 2 nonoverlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, receptor clustering on the cell surface, leading to internalization of biparatopic binding and potent immune effector functions, including antibody-dependent cellulose cytotoxicity, antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity leading to encouraging antitumor activity in patients.

轉到幻燈片 17。我將詳細闡述我之前關於 Zanidatamab 的評論。 Zanidatamab 是一種新型雙特異性抗體，可以同時結合 HER2 的 2 個非重疊表位，稱為雙互補位結合。這種獨特的設計導致多種作用機制，包括雙HER2 信號阻斷、細胞表面受體聚集，導致雙互補位結合的內化和有效的免疫效應功能，包括抗體依賴性纖維素細胞毒性、抗體依賴性細胞吞噬作用和補體-依賴性細胞毒性導致鼓勵患者的抗腫瘤活性。

Zanidatamab has shown compelling activity across a broad range of HER2-positive tumors and we presented promising efficacy and early survival data at both ASCO and ASCO GI this year. Additional data presentations are planned for later this year, including quality of life outcomes from the HERIZON-BTC-01 pivotal study at the European Society of Medical Oncology Annual Congress.

Zanidatamab 在廣泛的 HER2 陽性腫瘤中顯示出引人注目的活性，我們今年在 ASCO 和 ASCO GI 上展示了有希望的療效和早期生存數據。計劃於今年晚些時候發布更多數據，包括歐洲腫瘤內科學會年會上 HERIZON-BTC-01 關鍵研究的生活質量結果。

This slide speaks to our development strategy for Zanidatamab, which is focused on 4 key areas: First, target areas with no approved HER2 agents, such as the significant unmet need second-line HER2-positive BTC as well as other solid tumors. Second, maximize the opportunity in GEA and other HER2-positive tumors, where we believe Zanidatamab has the potential to be the HER2-targeted treatment of choice, simpleminded HER2-targeted agents. Compelling data demonstrated that Zanidatamab has the potential to be a foundational treatment for patients with HER2-positive GEA.

這張幻燈片講述了我們 Zanidatamab 的開發策略，該策略重點關注 4 個關鍵領域：首先，尚未批准 HER2 藥物的目標領域，例如未滿足的重大需求二線 HER2 陽性 BTC 以及其他實體瘤。其次，最大化 GEA 和其他 HER2 陽性腫瘤的機會，我們相信 Zanidatamab 有潛力成為 HER2 靶向治療的首選，簡單的 HER2 靶向藥物。令人信服的數據表明 Zanidatamab 有潛力成為 HER2 陽性 GEA 患者的基礎治療方法。

Third, we see substantial opportunity in settings for Zanidatamab could be used in combination with standard of care for other novel therapies, particularly in breast cancer and in earlier lines of treatment. Fourth, we plan to build upon the compelling activity we've seen across a broad range of HER2-positive tumors to address the patient need in additional tumor types. We believe this approach will allow us to deliver an important new therapeutic option to patients and maximize the value of Zanidatamab.

第三，我們看到 Zanidatamab 的大量機會可以與其他新型療法的護理標準相結合，特別是在乳腺癌和早期治療中。第四，我們計劃以我們在廣泛的 HER2 陽性腫瘤中看到的引人注目的活動為基礎，以滿足患者對其他腫瘤類型的需求。我們相信，這種方法將使我們能夠為患者提供一種重要的新治療選擇，並最大限度地發揮 Zanidatamab 的價值。

On Slide 18, I want to provide more insight into our excitement about the long-term potential of Zanidatamab, which we believe could go beyond addressing significant unmet needs in BTC and GEA, which include breast cancer as well as multiple additional cancers that overexpress HER2. With the potential to transform the current standard of care in multiple HER2-positive cancers, we are committed to rapidly advancing and expanding our development program. We believe that Zanidatamab has the opportunity to be a differentiated bispecific treatment of choice for HER2-positive cancers.

在幻燈片18 中，我想更深入地闡述我們對Zanidatamab 長期潛力的興奮，我們相信Zanidatamab 的作用不僅限於解決BTC 和GEA 中未滿足的重大需求，其中包括乳腺癌以及多種過度表達HER2 的其他癌症。由於有可能改變多種 HER2 陽性癌症的當前護理標準，我們致力於快速推進和擴大我們的開發計劃。我們相信 Zanidatamab 有機會成為 HER2 陽性癌症的差異化雙特異性治療選擇。

We expect to enter the market first in second-line BTC where physicians will gain important experience with Zanidatamab. The approach is supported by recent compelling data presented at ASCO in previously treated HER2-positive BTC. We are pleased to share that we are planning for a potentially accelerated approval of Zanidatamab in second-line BTC based on the HERIZON-BTC-01 data, and are working to rapidly bring this therapy to patients in critical need. We've shared the impressive second-line data with the FDA and have alignment on a confirmatory trial in first-line metastatic BTC where there remains an important unmet patient need. We are continuing to work with FDA regarding time lines and as our conversations progress, we will expect to be able to provide further updates.

我們預計首先進入二線 BTC 市場，醫生將獲得 Zanidatamab 的重要經驗。該方法得到了 ASCO 最近在先前治療的 HER2 陽性 BTC 中提供的令人信服的數據的支持。我們很高興地告訴大家，我們正計劃根據 HERIZON-BTC-01 數據加速批准 Zanidatamab 在二線 BTC 中的應用，並努力將這種療法迅速帶給急需的患者。我們已經與 FDA 分享了令人印象深刻的二線數據，並就一線轉移性 BTC 的驗證性試驗進行了協調，該領域仍然存在重要的未滿足的患者需求。我們將繼續與 FDA 就時間表進行合作，隨著我們對話的進展，我們將期望能夠提供進一步的更新。

Following market entry in BTC, we expect to have a path to approval in first-line GEA with a supplemental BLA submission, which provides a more streamlined approval process compared to a full BLA. With the treatment landscape evolving following recent data readouts, we continue to strongly believe that substantial opportunity remains to address the unmet patient need in first-line GEA, including the HER2-positive PD-L1 negative patient population where the standard of care remains trastuzumab plus chemotherapy.

進入 BTC 市場後，我們預計將通過提交補充 BLA 獲得一線 GEA 的批准，與完整的 BLA 相比，這提供了更簡化的批准流程。隨著最近數據公佈後治療格局的演變，我們仍然堅信，仍有大量機會來解決一線GEA 中未滿足的患者需求，包括HER2 陽性PD-L1 陰性患者群體，其護理標準仍然是曲妥珠單抗加曲妥珠單抗化療。

For patients who are PD-L1 positive, we continue to believe that Zanidatamab has the potential to be a HER2-targeted treatment of choice, while also combining with BeiGene Tislelizumab in order to treat those who are eligible to receive anti-PD-1 therapy for GEA. Further, there remains an opportunity to move into earlier stages of GEA, where we see the potential to help those patients prior to the metastatic setting in the neoadjuvant and adjuvant settings.

對於PD-L1陽性患者，我們仍然相信Zanidatamab有潛力成為HER2靶向治療的選擇，同時也與百濟神州替雷利珠單抗聯合治療那些有資格接受抗PD-1治療的患者對於 GEA。此外，仍有機會進入 GEA 的早期階段，我們認為有可能在新輔助和輔助治療中幫助那些在轉移之前的患者。

GEA represents a significantly larger patient opportunity compared to BTC. And a prior approval in BTC may also accelerate adoption into GEA treatment guidelines and protocols. We look forward to additional data from the ongoing pivotal Phase III GEA trial, HERIZON-GEA-01 expected to read out in 2024, which may support U.S. 10 global regulatory submissions.

與 BTC 相比，GEA 代表了更大的患者機會。 BTC 的事先批准也可能會加速 GEA 治療指南和方案的採用。我們期待正在進行的關鍵 III 期 GEA 試驗 HERIZON-GEA-01 的更多數據，預計將於 2024 年公佈，這可能支持美國 10 個全球監管部門的提交。

Breast cancer also represents a considerable opportunity supported by promising early data as monotherapy in multiple combinations across lines of therapy. Based on the efficacy and safety seen in studies to date, we believe Zanidatamab is well suited for early-stage disease, including potential use of neoadjuvant and adjuvant therapy. Further, we believe there is potential to help patients previously treated with trastuzumab deruxtecan or T-DXd or for those patients who are ineligible to receive treatment with T-DXd.

乳腺癌也代表了一個相當大的機會，有希望的早期數據支持作為跨療法多種組合的單一療法。根據迄今為止研究中發現的療效和安全性，我們相信 Zanidatamab 非常適合早期疾病，包括新輔助和輔助治療的潛在用途。此外，我們相信有可能幫助之前接受過 trastuzumab deruxtecan 或 T-DXd 治療的患者或那些不適合接受 T-DXd 治療的患者。

Zanidatamab has also shown promise in HER2-positive and hormone receptor positive breast cancer as part of a novel combination. Supporting this, we have ongoing trials in neoadjuvant breast cancer and the opportunity to expand into both combination regimens and later lines of therapy in HER2-positive and HER2 HR-positive breast cancer. We are also evaluating Zanidatamab through multiple earlier stage trials in other tumor types, where few HER2-targeted treatment options are available. Zanidatamab has shown clinical activity across a diverse set of HER2-positive indications such as colorectal cancer, non-small cell lung cancer and multiple other cancers where there remain a few targeted treatment options available to the patients.

作為一種新型組合的一部分，Zanidatamab 在治療 HER2 陽性和激素受體陽性乳腺癌方面也顯示出前景。為了支持這一點，我們正在進行新輔助乳腺癌試驗，並有機會擴展到 HER2 陽性和 HER2 HR 陽性乳腺癌的聯合治療方案和後續治療方案。我們還通過針對其他腫瘤類型的多項早期試驗來評估 Zanidatamab，這些腫瘤類型幾乎沒有 HER2 靶向治療方案。 Zanidatamab 已在多種 HER2 陽性適應症中顯示出臨床活性，例如結直腸癌、非小細胞肺癌和多種其他癌症，在這些癌症中，患者仍有一些靶向治療選擇。

Turning to Slide 19. I would like to highlight JZP150, our novel, highly selective fatty acid amide hydrolase or FAAH inhibitor, is currently in clinical development for the potential treatment of PTSD with Phase II top line data expected later this year. PTSD is a psychiatric disorder that affect millions of people and patients frequently have uncontrolled symptoms that impact their ability to perform activities of daily living and function socially.

轉向幻燈片19。我想強調一下JZP150，我們的新型高選擇性脂肪酸酰胺水解酶或FAAH 抑製劑，目前正在進行臨床開發，用於潛在治療PTSD，預計今年晚些時候將獲得II 期頂線數據。創傷後應激障礙（PTSD）是一種影響數百萬人的精神疾病，患者經常出現不受控制的症狀，影響他們進行日常生活活動和社交功能的能力。

Only 2 antidepressants have received approval from FDA for the treatment of PTSD symptoms in the past 20 years. Current first-line pharmacological treatment for PTSD such as selective serotonin reuptake inhibitors mitigate some symptoms of PTSD that are not designed to address the core underlying problem, fear extinction learning and its consolidation. Response rates to existing pharmacological treatments rarely exceed 60% and even fewer patients achieved clinical remission.

過去 20 年來，只有 2 種抗抑鬱藥獲得 FDA 批准用於治療 PTSD 症狀。目前針對 PTSD 的一線藥物治療，例如選擇性血清素再攝取抑製劑，可以減輕 PTSD 的一些症狀，但這些症狀並非旨在解決核心的潛在問題，即恐懼消退學習及其鞏固。現有藥物治療的緩解率很少超過 60%，達到臨床緩解的患者更少。

We have been granted FDA Fast Track designation for JZP150, underscoring the significant unmet needs of PTSD patients. JZP150 is a once-daily oral medication that has the potential to impact the pathophysiology and symptoms of PTSD. Data to date have demonstrated benefits with fear extension and stress response in healthy volunteers.

我們的 JZP150 已獲得 FDA 快速通道指定，強調了 PTSD 患者的重大未滿足需求。 JZP150 是一種每日一次的口服藥物，有可能影響 PTSD 的病理生理學和症狀。迄今為止的數據已經證明，健康志願者的恐懼延伸和壓力反應有好處。

Slide 20 shows the PTSD pathophysiology and JZP150's mechanism of action and treatment rationale. PTSD can result from direct or indirect exposure to traumatic experiences and events. Individuals with PTSD have intense and disturbing thoughts and feelings related to their experience that persists long after their dramatic event and they may relive the event through flashbacks or nightmares and feel sadness, fear, anger and detachment from other people.

幻燈片 20 顯示了 PTSD 病理生理學和 JZP150 的作用機制和治療原理。創傷後應激障礙（PTSD）可能是由於直接或間接接觸創傷性經歷和事件而導致的。患有創傷後應激障礙(PTSD) 的人會產生與他們的經歷相關的強烈且令人不安的想法和感受，這些想法和感受在戲劇性事件發生後很長一段時間內持續存在，他們可能會通過閃回或噩夢重溫該事件，並感到悲傷、恐懼、憤怒和與他人的疏離。

In PTSD, fear extinction deficits contribute to the persistence of traumatic memories, interventions to promote fear extinction learning or foundation of PTSD treatment. Preclinical and clinical data indicates that exposure to stress and anxiety is associated with activation of fatty acid amide hydrolase or FAAH. Inhibition of FAAH has the potential to directly target pathophysiological processes of PTSD. FAAH is the enzyme responsible for the degradation of anandamide.

在 PTSD 中，恐懼消退缺陷有助於創傷記憶的持續存在，促進恐懼消退學習的干預措施或 PTSD 治療的基礎。臨床前和臨床數據表明，壓力和焦慮與脂肪酸酰胺水解酶或 FAAH 的激活有關。抑制 FAAH 有可能直接針對 PTSD 的病理生理過程。 FAAH 是負責降解 anandamide 的酶。

Anandamide is reduced in PTSD and failure of anandamide to return to normal levels can result in a number of behavioral conditions underlying PTSD, including increased anxiety and impaired extinction processing of emotional memory. Inhibition of FAAH results in an increase in anandamide. This has been shown to reduce anxiety, improved fear extinction and recall and improved sleep architecture and self-reported sleep quality. JZP150 is a potent, highly-selective and irreversible inhibitor of FAAH designed to address the underlying cause of PTSD.

Anandamide 在 PTSD 中減少，並且 Anandamide 未能恢復到正常水平可能會導致 PTSD 潛在的許多行為狀況，包括焦慮增加和情緒記憶消退處理受損。抑制 FAAH 會導致 anandamide 增加。事實證明，這可以減少焦慮，改善恐懼消除和回憶，改善睡眠結構和自我報告的睡眠質量。 JZP150 是一種有效、高選擇性和不可逆的 FAAH 抑製劑，旨在解決 PTSD 的根本原因。

Moving to Slide 21. We have outlined the design of the Phase II PTSD trial. The primary endpoint of the trial is change in total symptom severity score using the clinician-administered PTSD scale or CAPS-5 from baseline to the end of treatment. CAPS-5 is a structured 30-item clinical interview as a validated instrument considered the standard for diagnosing and assessing patients with PTSD and is an endpoint that has been determined to be appropriate for regulatory purposes.

轉向幻燈片 21。我們概述了第二階段 PTSD 試驗的設計。該試驗的主要終點是使用臨床醫生管理的 PTSD 量表或 CAPS-5 從基線到治療結束時總症狀嚴重程度評分的變化。 CAPS-5 是一項結構化的 30 項臨床訪談，作為一種經過驗證的工具，被認為是診斷和評估 PTSD 患者的標準，並且是已確定適合監管目的的終點。

Beyond PTSD diagnosis, it also allows physicians to evaluate the severity of symptoms, an impact on social and occupational function. The trial has several secondary endpoints, including changes in scores on clinical global impressions of severity and the patient global impression of severity scales from baseline to the end of treatment. The ongoing trial is enrolling approximately 270 patients and assessing 2 doses of JZP150 compared to placebo, which we believe adequately powers the trial to assess whether JZP150 is clinically meaningful in this patient population. We expect top line data by the end of this year. We are excited about the potential of JZP150 and look forward to updating you on our progress.

除了 PTSD 診斷之外，它還允許醫生評估症狀的嚴重程度以及對社會和職業功能的影響。該試驗有幾個次要終點，包括從基線到治療結束時臨床嚴重程度總體印象的評分變化以及患者嚴重程度的總體印象評分的變化。正在進行的試驗正在招募約 270 名患者，並評估 2 劑 JZP150 與安慰劑的比較，我們相信這足以為該試驗評估 JZP150 在該患者群體中是否具有臨床意義提供動力。我們預計今年年底將公佈頂線數據。我們對 JZP150 的潛力感到興奮，並期待向您通報我們的最新進展。

Turning to Slide 22. We are pleased to recently receive IND clearance for JZP898 and expect to initiate a Phase I trial later this year. JZP898 is an engineered interferon alpha cytokine pro drop that is activated specifically within the tumor microenvironment where it can stimulate interferon alpha receptors on cancer fighting immune effector cells. High-dose interferon alpha therapy is approved in multiple tumor types, but is used sparingly based on its toxicity profile. Systemic delivery of cytokines can cause serious toxicities in peripheral tissues. This leads to poor clinical outcomes given ineffective antitumor immune activation and unmanageable toxicity in patients.

轉向幻燈片 22。我們很高興最近收到 JZP898 的 IND 批准，並預計在今年晚些時候啟動 I 期試驗。 JZP898 是一種工程化干擾素α細胞因子前滴劑，在腫瘤微環境中特異性激活，可以刺激抗癌免疫效應細胞上的干擾素α受體。高劑量干擾素α療法已被批准用於多種腫瘤類型，但由於其毒性特徵而很少使用。細胞因子的全身遞送可在外周組織中引起嚴重的毒性。由於抗腫瘤免疫激活無效和患者無法控制的毒性，這導致臨床結果不佳。

JZP898 is conditionally activated interferon alpha which is selectively activated in the tumor microenvironment. Through this approach, biologically relevant exposures are coupled with optimal cytokine potency while limiting toxicity in other tissues. We are excited to bring this novel molecule into the clinic later this year. Overall, our R&D team continues to advance multiple programs from our neurosciences and oncology pipelines, and we're looking forward to multiple near-term data readouts.

JZP898是條件激活的干擾素α，在腫瘤微環境中選擇性激活。通過這種方法，生物學相關的暴露與最佳細胞因子效力相結合，同時限制其他組織的毒性。我們很高興能在今年晚些時候將這種新型分子帶入臨床。總體而言，我們的研發團隊繼續推進神經科學和腫瘤學管道中的多個項目，我們期待多個近期數據讀出。

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

現在我將把電話轉給蕾妮，了解最新的財務情況。蕾妮？

Thanks, Rob. I'll start with our top and bottom line results on Slide 24. As a reminder, our full financial results are available in our press release and 10-Q. In the second quarter of 2023, we achieved $957 million in total revenues. This was driven by growth of our key products in both neuroscience and oncology, including another quarter of double-digit growth of Xywav, Epidiolex and Rylaze compared to 2Q '22.

謝謝，羅布。我將從幻燈片 24 上的頂線和底線結果開始。提醒一下，我們的完整財務結果可在我們的新聞稿和 10-Q 中找到。 2023 年第二季度，我們實現總收入 9.57 億美元。這是由我們在神經科學和腫瘤學領域的關鍵產品的增長推動的，包括與 2022 年第二季度相比，Xywav、Epidiolex 和 Rylaze 又實現了四分之一的兩位數增長。

We're particularly pleased with the continued trajectory of Xywav even with competition since the beginning of the year, coupled with the continued Epidiolex momentum and strong growth for Rylaze, we saw total revenue increased 3% compared to 2Q '22. Our disciplined capital allocation and focus on operational excellence drove adjusted net income of $325 million, growth of 6% compared to the same quarter in 2022.

我們對Xywav 的持續發展軌跡感到特別滿意，即使自今年年初以來一直存在競爭，再加上Epidiolex 的持續勢頭和Rylaze 的強勁增長，我們看到總收入與2022 年第二季度相比增長了3% 。我們嚴格的資本配置和對卓越運營的關注推動調整後淨利潤達到 3.25 億美元，與 2022 年同季度相比增長 6%。

We continue to generate significant cash from our business, recording approximately $617 million of cash from operations in the first half of 2023, an increase of more than $100 million compared to the same period in 2022. Our strong overall financial position means we have significant flexibility to invest in priority commercial and R&D programs as well as corporate development opportunities. Corporate development is a core component of Vision 2025, and we remain active in exploring opportunities to expand our commercial portfolio and pipeline.

我們繼續從業務中產生大量現金，2023 年上半年運營現金約為 6.17 億美元，與 2022 年同期相比增加超過 1 億美元。我們強勁的整體財務狀況意味著我們擁有顯著的靈活性投資於優先商業和研發項目以及企業發展機會。企業發展是 2025 年願景的核心組成部分，我們將繼續積極探索擴大商業產品組合和渠道的機會。

Turning to Slide 25. We are updating our total 2023 revenue guidance to a range of $3.725 billion to $3.875 billion, reflecting a $25 million increase at the midpoint. This update is underpinned by an increase of $20 million at the midpoint of our neuroscience revenue guidance. Our increased 2023 neuroscience revenue guidance incorporates our continued confidence in the durability of our oxybate franchise in part based on the performance and growth of Xywav during the first half of the year, a time period in which we saw the introduction of high sodium oxybate competition.

轉向幻燈片 25。我們將 2023 年總收入指導更新為 37.25 億美元至 38.75 億美元範圍，中間增加了 2500 萬美元。此次更新的基礎是我們的神經科學收入指導中點增加了 2000 萬美元。我們增加的2023 年神經科學收入指引體現了我們對羥丁酸鈉特許經營權持久性的持續信心，部分原因是Xywav 在今年上半年的表現和增長，在這段時期我們看到了高羥丁酸鈉競爭的引入。

With regard to high sodium authorized generics, we expect our royalties from Hikma, which is the only volume unlimited authorized generic to be significantly higher in the second half of 2023 relative to the first half. During the second half of 2023, the royalty rate from Hikma to Jazz becomes fixed at a rate where we and Hikma both have substantial economics. We also received royalties on other high sodium oxybate AGs, all of which are restricted to a low single-digit percentage of Xyrem sales volume.

關於高鈉授權仿製藥，我們預計 2023 年下半年從 Hikma（唯一一種數量不受限制的授權仿製藥）獲得的特許權使用費將顯著高於上半年。 2023 年下半年，從 Hikma 到 Jazz 的特許權使用費將固定在我們和 Hikma 都具有可觀經濟效益的費率。我們還收到其他高羥丁酸鈉 AG 的特許權使用費，所有這些都僅限於 Xyrem 銷量的低個位數百分比。

As Dan noted earlier, currently, only one additional AG has been launched. Our 2023 oncology guidance remains unchanged and reflects expectations of continued double-digit growth for this franchise led by Rylaze with a revenue range of $950 million to $1.05 billion and a midpoint of $1 billion.

正如 Dan 早些時候指出的，目前僅推出了另外一個 AG。我們的 2023 年腫瘤學指導保持不變，反映了對 Rylaze 領導的該系列產品持續兩位數增長的預期，收入範圍為 9.5 億美元至 10.5 億美元，中位數為 10 億美元。

Continuing to Slide 26. Our capital allocation strategy includes investment in commercial brands to drive top line growth in our pipeline to drive long-term growth and in corporate development where we remain actively engaged in assessing opportunities and which remains an important pillar of our growth strategy. We are maintaining our prior non-GAAP SG&A and R&D guidance for 2023.

繼續幻燈片26。我們的資本配置策略包括對商業品牌的投資，以推動我們管道中的營收增長，從而推動長期增長和企業發展，我們仍然積極參與評估機會，這仍然是我們增長戰略的重要支柱。我們維持之前的 2023 年非 GAAP SG&A 和研髮指引。

Consistent with our capital allocation strategy, our enhanced investment in R&D is a direct result of our success in diversifying and advancing our pipeline as well as prioritizing those programs that we believe will have the biggest impact for patients while delivering value and contributing to our growth. We believe there is tremendous unrecognized value potential in our stock and therefore, supported by our strong cash flows and aligned to our strategic and disciplined approach to capital allocation, we have resumed share repurchases under our existing repurchase program.

與我們的資本配置策略相一致，我們加大研發投資是我們成功實現產品線多元化和推進以及優先考慮那些我們認為將對患者產生最大影響的項目的直接結果，同時提供價值並為我們的增長做出貢獻。我們相信我們的股票存在巨大的未被認識到的價值潛力，因此，在我們強勁的現金流的支持下，並與我們的戰略和嚴格的資本配置方法保持一致，我們已經根據現有的回購計劃恢復了股票回購。

In the second quarter, we completed approximately $100 million of share repurchases. As of the end of the second quarter, approximately $336 million remained available for share repurchases under our current plan. Importantly, given our strong overall financial position, we are able to repurchase shares without compromising our ability to execute business development opportunities and invest in our innovative R&D program. On the bottom line, we expect to continue to deliver strong adjusted net income, or ANI, and have increased our non-GAAP ANI guidance to $1.29 billion to $1.34 billion, which implies a 41% year-over-year ANI growth at the midpoint.

第二季度，我們完成了約 1 億美元的股票回購。截至第二季度末，根據我們當前的計劃，仍有約 3.36 億美元可用於股票回購。重要的是，鑑於我們強勁的整體財務狀況，我們能夠在不損害我們執行業務發展機會和投資創新研發計劃的能力的情況下回購股票。總體而言，我們預計將繼續實現強勁的調整後淨利潤 (ANI)，並將我們的非 GAAP ANI 指引提高至 12.9 億美元至 13.4 億美元，這意味著 ANI 中點同比增長 41% 。

I would also like to highlight, we raised our non-GAAP adjusted EPS guidance to a range of $18.15 to $19, an increase of $1.20 at the midpoint, primarily driven by our increased revenue and ANI outlook as well as reductions in our fully diluted shares outstanding. The decrease to our weighted-average ordinary share guidance relates to both our share repurchase and to our recent irrevocable election to settle in cash the principal of our $575 million exchangeable senior notes due in 2024, thereby limiting potential dilution from these instruments.

我還想強調的是，我們將非GAAP 調整後每股收益指導上調至18.15 美元至19 美元，中點增加了1.20 美元，這主要是由於我們的收入和ANI 前景的增加以及完全稀釋股票的減少所致傑出的。我們加權平均普通股指引的下降與我們的股票回購和我們最近不可撤銷的選擇有關，即以現金結算2024 年到期的5.75 億美元可交換優先票據的本金，從而限制了這些工具的潛在稀釋。

With our strategic investments, expanding product portfolio, R&D progress and focus on operational excellence, we believe we are well positioned to achieve Vision 2025 and deliver further diversification, sustainable growth and enhanced value to patients and shareholders. I'd now like to turn the call back to Bruce.

憑藉我們的戰略投資、擴大產品組合、研發進展以及對卓越運營的關注，我們相信我們有能力實現 2025 年願景，並為患者和股東提供進一步的多元化、可持續增長和更高的價值。我現在想把電話轉回布魯斯。

Thanks, Renee. I'll conclude our prepared remarks on Slide 28. The first half of 2023 has been driven by focused execution and strong commercial results, evidenced by the durability of our oxybate franchise, continued growth of Epidiolex and strengthened Rylaze sales. We continue to advance our pipeline and invest in long-term growth, and we have as many as 4 late-stage data readouts through 2024 that have the potential to further diversify and transform our business.

謝謝，蕾妮。我將在幻燈片28 上結束我們準備好的發言。2023 年上半年是由專注的執行和強勁的商業業績推動的，我們的oxybate 特許經營權的持久性、Epidiolex 的持續增長和Rylaze 銷售的增強證明了這一點。我們繼續推進我們的產品線並投資於長期增長，到 2024 年我們擁有多達 4 個後期數據讀數，這些數據有可能進一步實現我們業務的多元化和轉型。

Our latest pipeline addition, Zanidatamab is approaching several near-term clinical and regulatory milestones. Given its applicability across multiple tumor types and lines of therapy, we believe Zanidatamab has $2 billion-plus in peak sales potential. We also remain focused on strategic capital allocation. With our strong cash flow, balance sheet and margins, we have the financial flexibility to make significant investments across commercial, pipeline and corporate development to drive sustainable growth and enhance value.

我們最新的產品線 Zanidatamab 正在接近幾個近期臨床和監管里程碑。鑑於其在多種腫瘤類型和治療方案中的適用性，我們相信 Zanidatamab 的峰值銷售潛力將超過 20 億美元。我們還繼續關注戰略資本配置。憑藉強勁的現金流、資產負債表和利潤率，我們擁有財務靈活性，可以在商業、管道和企業發展領域進行重大投資，以推動可持續增長並提升價值。

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

我們準備好的發言到此結束。我現在想將電話轉給接線員以開通問答線路。

(Operator Instructions) The first question comes from the line of Jason Gerberry with Bank of America.

（操作員說明） 第一個問題來自美國銀行的 Jason Gerberry 線路。

Mine is on the Phase III Zani GEA study that's going to read out first half next year. Can you help frame what sort of data we can expect on the primary efficacy measures, the PFS, the OS? Is this a first interim -- I'm just wondering if PFS and OS will be mature or the focus really is on ORR in this data cut.

我的研究正在進行 Zani GEA 第三階段研究，該研究將於明年上半年公佈。您能否幫助我們構建關於主要療效指標、PFS、OS 的預期數據類型？這是第一個過渡期嗎？我只是想知道 PFS 和 OS 是否會成熟，或者這次數據削減的重點實際上是 ORR。

Rob, maybe I'll throw that one to you.

羅布，也許我會把那個扔給你。

So just to clarify, what we said previously was in 2024, we didn't specify exactly when. And in that, we are referring to PFS as the initial readout. Does that clarify your question?

所以澄清一下，我們之前說的是 2024 年，但我們沒有具體說明具體時間。在此，我們將 PFS 稱為初始讀數。這能澄清你的問題嗎？

Yes.

是的。

The next question comes from the line of Joseph Thome with TD Cowen.

下一個問題來自 Joseph Thome 和 TD Cowen 的對話。

Maybe one on the upcoming PTSD readout. Maybe what's a clinically meaningful benefit on that cap scale? And when you talk about the type of patients enrolled or the on concomitant SSRI or the SRI treatment failures? Can you just put that in context a little bit for us, that would be great.

也許是關於即將發布的創傷後應激障礙 (PTSD) 讀數。也許在這個上限範圍內有什麼臨床意義的好處？當您談論入組患者的類型或同時使用 SSRI 或 SRI 治療失敗時？您能否為我們介紹一下這一點，那就太好了。

Yes. Go ahead, Rob.

是的。繼續吧，羅布。

Sure. So we haven't said specifically what treatment effect that we've powered to, but you could draw some of your own inferences by looking at the sample sizes, et cetera, that's listed on [ct.gov]. And you'll note that it's a placebo-controlled trial with 2 dose levels in the total sample size. Patients are allowed other concomitant medications.

當然。因此，我們還沒有具體說明我們已經達到了什麼治療效果，但您可以通過查看 [ct.gov] 上列出的樣本量等得出一些自己的推論。您會注意到，這是一項安慰劑對照試驗，總樣本量有 2 個劑量水平。患者可以同時服用其他藥物。

The next question comes from the line of Marc Goodman with Leerink Partners.

下一個問題來自 Marc Goodman 和 Leerink Partners。

Could you please give us a little more color on the comment that you made regarding the operational issues with the specialty pharmacy and the oxybate franchise and just give us a sense of how much you think it may have impacted patients in the quarter or whatever you think it may have impacted or is it impacting anything in the third quarter?

您能否就您對專業藥房和 oxybate 特許經營權的運營問題發表的評論提供更多信息，並讓我們了解您認為這可能對本季度患者或您認為的任何影響有多大它可能已經影響或者正在影響第三季度的任何事情嗎？

Thanks for the question, Marc. Kim, you want to take that?

謝謝你的提問，馬克。金，你想接受這個嗎？

Sure. I'd be happy to. So let me start out by saying that we continue to be very confident in the strength and durability of our activate franchise as low-sodium Xywav continues to be the oxybate of choice and the only approved therapy for IH. The decrease in total average active Jazz oxybate patients this quarter primarily reflects the expected impact to Xyrem as a result of Xywav adoption and the availability of AG Xyrem.

當然。我很樂意。首先我要說的是，我們仍然對我們的 activate 特許經營權的強度和持久性非常有信心，因為低鈉 Xywav 仍然是首選的羥丁酸鹽，也是唯一被批准的 IH 療法。本季度平均活躍 Jazz oxybate 患者總數的減少主要反映了 Xywav 的採用和 AG Xyrem 的可用性對 Xyrem 的預期影響。

In terms of Xywav and the average number of patients on Xywav exiting the quarter, there was what we're calling an operational change at our specialty pharmacy, which unfortunately caused delays in some Xywav patients getting their refills on time. So this has been addressed. And importantly, I think to understand is that the overall 2Q Xywav HCP and patient demand, the overall market demand for Xywav was in line with our expectations and with what we saw in prior quarters.

就 Xywav 和退出本季度使用 Xywav 的患者平均數量而言，我們的專業藥房發生了我們所說的運營變化，不幸的是，這導致一些 Xywav 患者按時獲得補充藥物的延誤。所以這個問題已經得到解決。重要的是，我認為要了解的是，第二季度 Xywav HCP 和患者的整體需求、Xywav 的整體市場需求符合我們的預期以及我們在前幾個季度看到的情況。

So this really was an issue at the pharmacy that affected patients. Some patients getting refills, not with the overall demand for Xywav. The benefits of reducing sodium intake in the market continue to resonate with our customers, and we're very confident in the growth opportunity for Xywav and the durability of the franchise. And while we expect Xyrem to continue to decline in line with the Xywav and AG adoption, as you heard, we've raised our full year 2023 financial guidance. and increased our neuroscience revenue guidance at the midpoint.

所以這確實是藥房影響患者的一個問題。一些患者得到了補充，但與 Xywav 的總體需求不符。市場上減少鈉攝入量的好處繼續引起我們客戶的共鳴，我們對 Xywav 的增長機會和特許經營權的持久性非常有信心。正如您所聽到的，雖然我們預計 Xyrem 將隨著 Xywav 和 AG 的採用而繼續下降，但我們已經提高了 2023 年全年財務指導。並在中點增加了我們的神經科學收入指導。

So overall, our increased neuroscience revenue guidance accounts for the performance and growth of Xywav during the first half of the year in the time period in which we saw the introduction of high-sodium oxybate competition. So our focus remains on continuing to grow the low-sodium Xywav, which is already, as you saw annualizing at well over $1 billion, and we remain very confident in the durability of the business.

因此，總體而言，我們增加的神經科學收入指導說明了 Xywav 在今年上半年我們看到高鈉羥丁酸競爭引入的時期的業績和增長。因此，我們的重點仍然是繼續發展低鈉 Xywav，正如您所看到的那樣，該產品的年化價值已遠超 10 億美元，而且我們對業務的持久性仍然非常有信心。

The next question comes from the line of Akash Tewari with Jefferies.

下一個問題來自 Akash Tewari 和 Jefferies 的對話。

So can you walk me through your confidence on the $2 billion sodium oxybate number for your long-term guidance. Let's say you continue to add about 250 IH patients a quarter until '25, that kind of implies IH will contribute about $600 million in sales by 2025. That means that your narcolepsy franchise, which is about $1.7 billion today only declined to about $1.4 billion for you to hit that $2 billion watermark. How do you achieve that with generic and Avadel launching? Like what are we missing here?

那麼，您能否向我介紹一下您對 20 億美元羥丁酸鈉的信心，以供您長期指導。假設您每個季度繼續增加約250 名IH 患者，直到25 年，這意味著到2025 年IH 將貢獻約6 億美元的銷售額。這意味著您的發作性睡病特許經營權（目前約為17 億美元）僅下降至約14 億美元讓您達到 20 億美元的大關。您如何通過推出通用藥物和 Avadel 來實現這一目標？比如我們在這裡缺少什麼？

Also, I think you've previously mentioned the majority of the erosion impact for the sodium oxybate franchise will occur in 2023. Is that still the case today given your revised neuro guide?

另外，我認為您之前提到過羥丁酸鈉特許經營權的大部分侵蝕影響將在 2023 年發生。考慮到您修訂後的神經指南，今天的情況仍然如此嗎？

Yes, Akash, thanks for the question. We outlined our confidence that oxybate business at Jazz would contribute about $2 billion towards Vision 2025 at the beginning of last year, at the beginning of 2022. Obviously, we reiterated that coming into '23, and we've now actually increased our short-term guidance in '23.

是的，阿卡什，謝謝你的提問。去年年初，即2022 年初，我們概述了我們的信心，即Jazz 的氧化酸鹽業務將為2025 年願景貢獻約20 億美元。顯然，我們重申了進入23 年的這一點，現在我們實際上已經增加了我們的短缺 - '23 中的術語指導。

As a reminder, what we meant by that $2 billion was the combined revenues from Xywav both in narcolepsy and in idiopathic hypersomnia, continued brand Xyrem sales and our royalties on any AGs that come to market through our system. And we continue to feel confident in that. You didn't specifically mention the royalties in your analysis, I'll remind you that the contribution from those royalties is expected to be significantly higher in the second half of 2023 relative to the first half and that the royalty structure we've disclosed from the Hikma relationship will actually reset up again in 2024.

提醒一下，我們所說的 20 億美元是指 Xywav 在嗜睡症和特發性嗜睡症領域的總收入、持續的 Xyrem 品牌銷售以及通過我們的系統進入市場的任何 AG 的特許權使用費。我們對此仍然充滿信心。您在分析中沒有具體提到特許權使用費，我要提醒您的是，這些特許權使用費的貢獻預計在 2023 年下半年將明顯高於上半年，而且我們披露的特許權使用費結構Hikma關係實際上將在2024 年再次恢復。

So it's the combination of all those things that get us to the durability. Our big focus, as Kim explained, is on growing Xywav. This is the longer, healthier choice for patients given the benefits of low sodium in this chronic treatment and we'd like to see more and more patients get the benefit of Xywav moving forward.

因此，正是所有這些因素的結合才讓我們獲得了耐用性。正如 Kim 解釋的那樣，我們的重點是發展 Xywav。鑑於這種長期治療中低鈉的益處，這對患者來說是更長久、更健康的選擇，我們希望看到越來越多的患者從 Xywav 中受益。

The next question comes from the line of David Amsellem with Piper Sandler.

下一個問題來自大衛·阿姆塞勒姆和派珀·桑德勒的對話。

So I wanted to come back to the Vision 2025 targets, particularly the $5 billion top line. It seems like the Street and the broader investor community is not quite there regarding the $5 billion target. So just can you articulate what you think we're all missing? Is it something surrounding Epidiolex? Is it Zanidatamab, for instance, is GEA, biliary tract cancer are both in that 2025 number? Just help us understand why there seems to be daylight between that target and what folks are modeling for 2025.

所以我想回到 2025 年願景目標，特別是 50 億美元的營收目標。華爾街和更廣泛的投資者群體似乎並沒有完全同意 50 億美元的目標。那麼你能說清楚你認為我們都缺少什麼嗎？是 Epidiolex 周圍有什麼東西嗎？例如，Zanidatamab、GEA、膽道癌都在 2025 年的數字中嗎？請幫助我們理解為什麼該目標與人們為 2025 年建模的目標之間似乎存在差距。

Yes. Well, let's review where we are towards Vision 2025. Again, we rolled this out at the beginning of 2022. We're 6 quarters in to a 4-year period. We're feeling very good about the performance of our business overall, both relative to our guidance for 2023, which has now been raised on both the top and the bottom line and our Vision 2025. I just spoke about oxybate and the durability of that franchise and the positive progress we're seeing with Xywav.

是的。好吧，讓我們回顧一下我們對 2025 年願景的進展情況。同樣，我們在 2022 年初推出了這一目標。四年期已經過去了 6 個季度。相對於我們對 2023 年的指導，我們對我們的整體業務表現感覺非常好，現在我們的頂線和底線以及我們的 2025 年願景都得到了提高。我剛剛談到了 oxybate 及其耐用性特許經營權以及我們在Xywav 上看到的積極進展。

But let me remind you that half of our business today is already coming from Epidiolex and oncology. We're seeing double-digit growth in our 3 lead assets, Xywav, Epidiolex and Rylaze which together are accounting for about 66% of our revenues. And when you look at the oxybate piece, Xyrem is now less than half of that piece of our business. So we've got growth coming in all of our key franchises, which we estimated would contribute in 2025 approximately $4.5 billion in aggregate.

但讓我提醒您，我們今天的一半業務已經來自 Epidiolex 和腫瘤學。我們看到我們的 3 個主要資產 Xywav、Epidiolex 和 Rylaze 實現了兩位數的增長，它們合計約占我們收入的 66%。當你看看羥丁酸鹽業務時，Xyrem 現在還不到我們業務的一半。因此，我們所有的主要特許經營權都在增長，我們估計到 2025 年將總共貢獻約 45 億美元。

We left a placeholder in Vision 2025 intentionally for our ongoing corporate development activities and said that products that were not part of our portfolio when we started Vision 2025 could contribute that last $0.5 billion. Zanidatamab may well contribute to that. We're not saying it's going to contribute all of the $500 million, to be clear, but that was something added to the portfolio after we began this process. And we remain very interested in continuing to access new commercial products and pipeline products through our corporate development efforts moving forward.

我們特意在《2025 年願景》中為我們正在進行的企業發展活動留下了一個佔位符，並表示在我們啟動《2025 年願景》時不屬於我們產品組合的產品可以貢獻最後 5 億美元。 Zanidatamab 很可能對此做出貢獻。需要明確的是，我們並不是說它將貢獻全部 5 億美元，但這是我們開始此流程後添加到投資組合中的東西。我們仍然非常有興趣通過我們的企業發展努力繼續獲得新的商業產品和管道產品。

Our financial position is strong. If you look at our cash and investments, about $1.4 billion. You look at our cash flow in the first half of the year, approaching $620 million. Our leverage is down. So we feel like we're well positioned to continue to bring in new assets. As we have over the company's history, if you go back any 2- to 3-year period in our history, you'll generally see us do a significant transaction. And we thought it was unfair to assume that we would suddenly stop doing transactions, particularly given our successful launches of a number of products in a row here and our strong financial position.

我們的財務狀況強勁。如果你看看我們的現金和投資，大約有 14 億美元。你看看我們上半年的現金流，接近6.2億美元。我們的槓桿率下降了。因此，我們覺得我們處於有利地位，可以繼續引入新資產。正如我們對公司歷史的了解一樣，如果你回顧我們歷史上的任何兩到三年，你通常會看到我們進行了一筆重大交易。我們認為假設我們會突然停止進行交易是不公平的，特別是考慮到我們在這裡連續成功推出了多種產品以及我們強大的財務狀況。

The next question comes from the line of Ami Fadia with Needham.

下一個問題來自阿米·法迪亞和李約瑟的對話。

Perhaps continuing on the vain of the placeholder for corporate development, can you talk about your level of confidence in being able to hit for a majority of that $500 million through some sort of business development? And where are your thoughts at currently in terms of alternative options, in terms of use of capital would you consider buying back more shares should you not be in a position to execute on such a deal?

也許繼續為企業發展佔位是徒勞的，您能談談您對能夠通過某種業務發展獲得這 5 億美元中的大部分的信心嗎？您目前在替代選擇方面的想法是什麼？在資本使用方面，如果您無法執行此類交易，您是否會考慮回購更多股票？

Renee, can you jump in on this one?

蕾妮，你能參與其中嗎？

Sure. I'm happy to. So Ami, we've talked quite a bit about our strategic and disciplined approach to capital allocation. And our priority, first and foremost, is investing in growth. So we're investing behind our commercial launches and growth programs. We're investing behind the pipeline, and we expect to continue to invest in corporate development. As Bruce mentioned previously, it has been an important pillar of growth for us, and we expect that to continue to be the case.

當然。我很高興。阿米，我們已經談論了很多關於我們的資本配置戰略和紀律方法。我們的首要任務是投資增長。因此，我們正在投資支持我們的商業發布和增長計劃。我們正在對管道進行投資，並且我們預計將繼續投資於企業發展。正如布魯斯之前提到的，它一直是我們增長的重要支柱，我們預計這種情況將繼續下去。

In addition, we also look at opportunities in terms of managing the balance sheet strategically. Bruce also mentioned we pretty quickly. So we're in a great position today to be opportunistic in terms of additional investments for the balance sheet. And we did take the opportunity, just given what we view as immense untapped value right now within the stock. We did take the opportunity to recommence share repurchases in the second quarter, and we think that was the right thing to do. In terms of future repurchases, we'll continue to look carefully at the opportunity set in front of us prioritizing growth.

此外，我們還關注戰略性管理資產負債表的機會。布魯斯也很快提到了我們。因此，我們今天處於有利的位置，可以在資產負債表的額外投資方面抓住機會。我們確實抓住了這個機會，只是考慮到我們認為該股票目前存在巨大的未開發價值。我們確實藉此機會在第二季度重新開始股票回購，我們認為這是正確的做法。在未來的回購方面，我們將繼續仔細審視擺在我們面前的機會，優先考慮增長。

And then specific to the $500 million placeholder, as you've heard on the call today, we're really excited about the opportunity for Zanidatamab. We think that's going to be an important program and eventually product for us and for patients. We don't expect that to cover a large majority of the $500 million, but it's certainly -- we certainly expect that to contribute. And then beyond that, we're quite active from a corporate development perspective. As you've heard me say previously, we're not going to overpay just to be able to meet this growth objective. We also don't think that we'll need to.

然後具體到 5 億美元的佔位符，正如您在今天的電話會議上聽到的那樣，我們對 Zanidatamab 的機會感到非常興奮。我們認為這將成為一個重要的計劃，並最終成為我們和患者的產品。我們預計這不會覆蓋 5 億美元中的大部分，但我們當然希望這會有所貢獻。除此之外，從企業發展的角度來看，我們非常積極。正如您之前聽我說過的，我們不會僅僅為了實現這一增長目標而付出過高的代價。我們也不認為我們需要這樣做。

We do think there are opportunities out there, both within neuroscience and oncology, but also within the rare and orphan segment more broadly. As you know, the vast majority of our commercial products currently do fall within that category, and we think there are applicable learnings in terms of working directly with patient groups and serving the needs of patients or underlying infrastructure those learnings can be shared both from our existing experience to other rare and orphan conditions.

我們確實認為，無論是在神經科學和腫瘤學領域，還是在更廣泛的罕見病和孤兒藥領域，都存在機會。如您所知，我們的絕大多數商業產品目前確實屬於該類別，我們認為在直接與患者群體合作以及滿足患者或底層基礎設施的需求方面存在適用的經驗教訓，這些經驗教訓可以從我們的其他罕見和孤兒病症的現有經驗。

So today, we feel quite confident in our ability to transact, we're well capitalized to be able to do so, as Bruce mentioned previously. And we think we've established a great track record as a partner of choice to be able to do so as well.

因此，今天，我們對自己的交易能力非常有信心，正如布魯斯之前提到的，我們有足夠的資本來做到這一點。我們認為，作為首選合作夥伴，我們已經建立了良好的記錄，也能夠做到這一點。

Our next question comes from the line of Gregory Renza with RBC Capital Markets.

我們的下一個問題來自加拿大皇家銀行資本市場部的 Gregory Renza。

Great. Bruce and team, congrats on the quarter. Bruce, maybe just a little bit on Epidiolex and just with respect to Dan's comments on the drivers for potential continued growth. Just curious if you can comment a bit on any particular areas or drivers that kind of outsized and helped to propel the growth that you're expecting certainly last quarter, first quarter, a little seasonality and seeing the momentum that you're speaking about now? I'm just curious how you see that playing out in the near term.

偉大的。布魯斯和他的團隊，祝賀這個季度。 Bruce，也許只是簡單介紹一下 Epidiolex，以及 Dan 對潛在持續增長驅動因素的評論。只是好奇您是否可以對任何特定領域或驅動因素發表評論，這些領域或驅動因素規模過大，有助於推動您所預期的上季度、第一季度的增長，一點季節性因素以及您現在所說的勢頭？我只是好奇你如何看待這種情況在短期內發生。

Yes. Greg, thanks for the question. Dan, do you want to take Epidiolex?

是的。格雷格，謝謝你的提問。丹，你想服用 Epidiolex 嗎？

Yes. Thanks, Bruce. So with Epidiolex, there's another quarter of double-digit growth with 15%, Greg. So really pleased to see the continued initiatives that we outlined on the call. Continued face-to-face interactions, very important in the treatment centers, getting to more offices, more prescribers. We've been enhancing our focus on the adult setting. In particular, in the U.S., we've got after long-term care settings and seeing increasing penetration there.

是的。謝謝，布魯斯。因此，Epidiolex 的另一個季度實現了兩位數增長，達到 15%，Greg。非常高興看到我們在電話會議中概述的持續舉措。持續的面對面互動，這在治療中心非常重要，可以接觸更多的辦公室、更多的處方醫生。我們一直在加強對成人環境的關注。特別是在美國，我們已經建立了長期護理機構，並看到那裡的滲透率不斷增加。

We've also been educating HCPs about the benefits of Epidiolex beyond seizure control. And that was highlighted in the BECOME data, which was presented at the end of last year, which talks about cognitive and behavioral benefits and we look forward to continuing to lean into that area, both with caregiver surveys and even interventional studies. And so we've got a real commitment to continuing to generate data, both within the indications and kind of outside those indications.

我們還一直在向 HCP 宣傳 Epidiolex 除了控制癲癇發作之外的其他益處。去年年底發布的 BECOME 數據強調了這一點，該數據討論了認知和行為益處，我們期待通過護理人員調查甚至乾預研究繼續深入該領域。因此，我們真正致力於繼續生成數據，無論是在適應症範圍內還是在這些適應症之外。

Outside the U.S., the launches continue to go well. We're at 23 countries globally. We've had 6 positive pricing reimbursement decisions to date in the U.S. -- sorry, outside the U.S. And importantly, we've got a Phase III study and what we think could be a very significant market for us with Epidiolex in Japan. And so that's enrolling nicely, and we look forward to providing updates in the coming quarters.

在美國以外的地區，產品發布繼續進展順利。我們的業務遍及全球 23 個國家/地區。迄今為止，我們在美國已經做出了6 項積極的定價報銷決定——抱歉，在美國之外。重要的是，我們已經進行了一項III 期研究，我們認為日本對Epidiolex 來說可能是一個非常重要的市場。因此，註冊情況很好，我們期待在未來幾個季度提供更新。

The next question comes from the line of Annabel Samimy with Stifel.

下一個問題來自安娜貝爾·薩米米（Annabel Samimy）和施蒂菲爾（Stifel）的關係。

Just a couple more on Epidiolex. So you mentioned a couple of times now expanded indications, the only indication we know that you're working on is the EMA indication. So are there others that we don't know about that you plan on expanding into? And also with the EU launch, we now have 23 countries approved, I guess, 5 in the major EU countries, but are all those countries all on board? Should we now see a significant expansion in Epidiolex ex-U.S.

Epidiolex 上還有更多內容。所以你提到了幾次現在擴展的指標，我們知道你正在研究的唯一指標是 EMA 指標。那麼，還有其他我們不知道但你們計劃擴張的領域嗎？隨著歐盟的啟動，我們現在有 23 個國家獲得批准，我猜，其中 5 個是在主要歐盟國家，但所有這些國家都同意了嗎？我們現在是否應該看到 Epidiolex 在美國以外地區的顯著擴張？

Rob, would you like to talk a little bit about some of the additional data we're generating with Epidiolex? And then maybe, Kim, you could talk a little bit about the potential for broader use of the product over time?

Rob，您想談談我們使用 Epidiolex 生成的一些附加數據嗎？ Kim，您也許可以談談該產品隨著時間的推移更廣泛使用的潛力？

Yes. So you're right that we're evaluating EMA and the objective there is to generate data and yet another seizure type. Adding to the 3 indications we have, really trying to demonstrate that Epidiolex is broadly active across different seizure types, regardless of the underlying etiology. We also continue to provide evidence around the indications we have, both in terms of anti-seizure effectiveness, but also in terms of other potential benefits of Epidiolex. And you heard Dan refer to the caretaker survey, and we continue to support and do studies along those lines as well.

是的。所以你說得對，我們正在評估 EMA，其目標是生成數據和另一種癲癇類型。除了我們擁有的 3 種適應症之外，我們還真正試圖證明 Epidiolex 在不同的癲癇類型中具有廣泛的活性，無論潛在的病因如何。我們還繼續圍繞我們所掌握的適應症提供證據，無論是在抗癲癇有效性方面，還是在 Epidiolex 的其他潛在益處方面。你聽到丹提到了看護者調查，我們也繼續支持並沿著這些方向進行研究。

Yes, sure, Rob. So I'll say that we've had very nice growth in the 3 indicated populations as well as growth over time and the base of prescribers that are utilizing Epidiolex. And what we see traditionally as our customers get more and more experience with the product, usually starting in the 3 indications they see what it can do for their patients in terms of seizure control and now beyond seizure control that frankly, they've been hearing about from caregivers since day 1 of the launch. And this really gives them the confidence to start using it more broadly across the spectrum of various seizure types and so forth.

是的，當然，羅布。所以我想說，我們在 3 個指定人群中取得了非常好的增長，並且隨著時間的推移以及使用 Epidiolex 的處方者基礎的增長。我們傳統上看到，隨著我們的客戶獲得越來越多的產品體驗，通常從3 個適應症開始，他們看到該產品在癲癇控制方面可以為患者帶來什麼，現在超出了癲癇控制範圍，坦率地說，他們一直在聽到自推出第一天起就來自護理人員。這確實讓他們有信心開始在各種癲癇類型等範圍內更廣泛地使用它。

So we're clearly not promoting it outside that, but this is what we hear from the providers once they get the experience they see the efficacy, they do start to utilize it earlier and more broadly across their patient population. And really, the data, as we've talked about, that we've been sharing to really increase the efficacy perception of the product, the clobazam combination data in and of itself, get them to stop and think about why am I reserving this for certain patient types. Most of my patients are on Clobazam, most of them could still benefit from additional seizure control or beyond seizure benefits and it really gets them to start thinking about I should be using this more, and more and more of these patients that are taking Clobazam.

因此，我們顯然不會在此之外推廣它，但這是我們從提供者那裡聽到的，一旦他們獲得了看到療效的經驗，他們就會開始更早、更廣泛地在患者群體中使用它。事實上，正如我們所討論的，我們一直在分享的數據，以真正提高產品的功效認知，氯巴扎姆組合數據本身，讓他們停下來思考為什麼我要保留這個對於某些患者類型。我的大多數患者都在服用氯巴扎姆，他們中的大多數人仍然可以從額外的癲癇發作控製或癲癇發作益處之外受益，這確實讓他們開始思考我應該更多地使用這種藥物，越來越多的患者正在服用氯巴扎姆。

Our next question comes from the line of Jeff Hung with Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Jeff Hung。

For Rylaze, you've talked about focusing on adolescents and young adults. Can you talk a little bit more about how that's going and how much of that opportunity remains to be addressed?

對於 Rylaze，您談到了關注青少年和年輕人。您能多談談進展情況以及還有多少機會有待解決嗎？

Yes. Kim?

是的。金？

Sure, love to. I love talking about Rylaze. What we've really seen with Rylaze is just lack of excitement in general. And I think as we told you early on, it didn't take very long for health care providers to have confidence in the supply and to return to best clinical practice in terms of switching patients at the first sign of hypersensitivity. At this point in the pediatric market, it's been added almost universally to the protocols in that setting. So at the beginning of this year, we did tell you that we were looking to start trying to expand the adolescent and young adult market.

當然，喜歡。我喜歡談論 Rylaze。我們在 Rylaze 身上真正看到的是總體上缺乏興奮感。我認為，正如我們早些時候告訴您的那樣，醫療保健提供者沒過多久就對供應產生了信心，並在出現過敏症的第一個跡象時就更換患者方面恢復了最佳臨床實踐。目前，在兒科市場，它幾乎已普遍添加到該環境的協議中。因此，在今年年初，我們確實告訴過您，我們正在尋求開始嘗試擴大青少年和年輕人市場。

There was quite a bit of usage -- a fair amount of usage of the product in adolescents and young adults that were being treated in the pediatric center per pediatric protocol but the adult centers were less educated, familiar and experienced with using Rylaze in this setting. And so we've gone out there this year. We have now spent 2 quarters educating them on the product, about the importance of switching as quickly as possible when they see a hypersensitivity reaction. And we see nice orders coming through and a nice growth rate happening in this setting. So we don't think we're done. We haven't gotten all of these centers to start using it. Some of them are still dabbling.

有相當多的使用情況——根據兒科方案在兒科中心接受治療的青少年和年輕人中有相當多的使用該產品，但成人中心在這種情況下使用 Rylaze 的教育程度、熟悉度和經驗較少。所以我們今年就去了那裡。我們現在已經花了兩個季度的時間對他們進行產品教育，讓他們了解當他們出現過敏反應時盡快轉換的重要性。我們看到在這種情況下出現了不錯的訂單和良好的增長率。所以我們認為我們還沒有完成。我們還沒有讓所有這些中心開始使用它。其中一些仍在涉足。

So there definitely is some more growth to be had there. And I think it's important to remember that in the adult setting, because this is a weight-based product, the average dose is higher than in the pediatric center. So each adult patient is worth more. So we're really pleased with Rylaze at this date, but we think there's a little bit more room to grow here in the U.S. and then, of course, ex U.S.

因此，那里肯定會有更多的增長。我認為重要的是要記住，在成人環境中，因為這是一種基於體重的產品，所以平均劑量高於兒科中心。因此，每個成年患者都更有價值。因此，我們目前對 Rylaze 感到非常滿意，但我們認為在美國還有更大的發展空間，當然，在美國以外的市場也有更大的發展空間。

Our next question comes from the line of Balaji Prasad with Barclays.

我們的下一個問題來自巴拉吉·普拉薩德 (Balaji Prasad) 與巴克萊銀行 (Barclays) 的對話。

This is Xiao on for Balaji. Just a quick one on your (inaudible) program. On the data for TAK-994 that was recently published on New England Journal of Medicine and the factor for liver toxicity for TAK-994 was the impact of reactive metabolics. So Takeda also mentioned that TAK-861 and TAK-994 do have the overlapping metabolic pathways. So do you think JZP441 is well differentiated with TAK-994 to avoid this issue?

我是巴拉吉的曉。只是簡單介紹一下您的（聽不清）程序。根據最近發表在《新英格蘭醫學雜誌》上的 TAK-994 數據，TAK-994 的肝毒性因素是反應性代謝的影響。所以武田還提到TAK-861和TAK-994確實有重疊的代謝途徑。那麼您認為JZP441與TAK-994有很好的差異化來避免這個問題嗎？

Rob?

搶？

Yes, thank you for the question. So the liver toxicity associated with 994 was known at the time that we entered into the partnership with Sumitomo, and we focused on chemical series that we thought were distinct enough such that, that wouldn't -- at risk of liver toxicity wouldn't be carried over. And so we do think that our molecule is substantially differentiated from the chemical series that you referred to.

是的，謝謝你的提問。因此，在我們與住友建立合作夥伴關係時，與 994 相關的肝臟毒性是已知的，我們專注於我們認為足夠獨特的化學系列，這樣，就不會 - 存在肝臟毒性的風險被結轉。因此，我們確實認為我們的分子與您提到的化學系列有很大不同。

The next question comes from the line of Mohit Bansal with Wells Fargo.

下一個問題來自富國銀行的莫希特·班薩爾 (Mohit Bansal)。

Great. Congrats on all the progress. So maybe like one question regarding the authorized generics of Xyrem, do you think they will have any impact on IH market as such because in our talk to doctors, they think that they can prescribe it as long as payers cover it -- payers would probably cover it. So do you see this as a threat because doctors could use it off-label?

偉大的。祝賀所有的進展。因此，也許就像有關Xyrem 授權仿製藥的一個問題一樣，您認為它們會對IH 市場產生任何影響嗎？因為在我們與醫生的交談中，他們認為只要付款人支付費用，他們就可以開處方-付款人可能會蓋住它。那麼您是否認為這是一種威脅，因為醫生可以在標籤外使用它？

Yes. Well, I'll remind you that Xyrem did not do a comprehensive clinical program in the way that Xywav has in IH. There's slightly different dosing information in the label. And while you're right that physicians can prescribe the product that does not always mean that, that product will be successfully reimbursed.

是的。好吧，我要提醒您的是，Xyrem 並沒有像 Xywav 在 IH 中那樣開展全面的臨床計劃。標籤上的劑量信息略有不同。雖然您認為醫生可以開出該產品的處方是正確的，但這並不總是意味著該產品將成功報銷。

Kim, any comments you want to make on the marketplace?

Kim，您想對市場發表什麼評論嗎？

Yes, sure. So yes, we've seen traditionally the payer -- that HCPs have had trouble getting coverage for oxybate for idiopathic hypersomnia because payers restricted it. With the introduction of Xywav for idiopathic hypersomnia we have achieved nice coverage as we do with narcolepsy of 90% of commercial lives having coverage. There usually is utilization management criteria in place there and certainly heavier utilization management criteria around non-indicated products. So we feel confident that while it's a small portion of health care plans may cover high sodium oxybate in particular, the AG for idiopathic hypersomnia, most of them are following the FDA-approved label. And Xywav is the only FDA-approved treatment for idiopathic hypersomnia.

是的，當然。所以，是的，我們傳統上看到付款人——醫療保健專業人士很難獲得針對特發性嗜睡症的羥丁酸保險，因為付款人對其進行了限制。隨著針對特發性嗜睡症的 Xywav 的推出，我們已經實現了很好的覆蓋範圍，就像我們對 90% 的商業生活覆蓋的發作性睡病一樣。通常有適當的利用率管理標準，當然還有圍繞非指定產品的更重的利用率管理標準。因此，我們有信心，雖然醫療保健計劃的一小部分可能涵蓋高羥丁酸鈉，特別是治療特發性嗜睡症的 AG，但大多數計劃都遵循 FDA 批准的標籤。 Xywav 是 FDA 批准的唯一一種治療特發性睡眠過度的藥物。

And Rob, maybe you could just expand a little bit on that slightly different dosing information?

羅布，也許你可以稍微擴展一下稍微不同的劑量信息？

Yes, Bruce, specifically with regard to narcolepsy or IH or?

是的，布魯斯，特別是關於發作性睡病或 IH 或？

I meant IH, but you can talk about dosing flexibility generally.

我的意思是 IH，但您可以普遍談論劑量靈活性。

Sure. So starting with IH then, the clinical trial allowed for an initial dose of up to 6 grams. And at the time, it was designed that way because there was some uncertainty around whether IH patients would make up to take that second dose. What we found in the clinical trials that with initiation of Xywav, patients with IH improved substantially. And in fact, we're able to go ahead and take the second dose. And overall, that was the more common dosing regimen, even though in the trial, and we find that to be the case in clinical practice as well. Along those lines for narcolepsy, as you know, Xywav also has dosing flexibility to allow for uneven doses. And we find that patients really do prefer this. Oftentimes, schedules are different from 1 patient to another. But even within a patient, schedules made different day to day, week days, weekends depending on family obligations, and they like the flexibility of uneven doses potentially.

當然。因此從 IH 開始，臨床試驗允許初始劑量高達 6 克。當時之所以如此設計，是因為 IH 患者是否會補充服用第二劑存在一些不確定性。我們在臨床試驗中發現，開始使用 Xywav 後，IH 患者的病情明顯改善。事實上，我們可以繼續服用第二劑。總的來說，即使在試驗中，這也是更常見的給藥方案，我們發現臨床實踐中也是如此。如您所知，針對發作性睡病，Xywav 還具有劑量靈活性，可以允許劑量不均勻。我們發現患者確實更喜歡這個。通常，每個患者的時間表都不同。但即使在患者體內，根據家庭義務，每天、工作日、週末的時間表也會有所不同，而且他們可能喜歡不均勻劑量的靈活性。

The next question comes from the line of Joon Lee with Truist Securities.

下一個問題來自 Truist Securities 的 Joon Lee。

Congrats on the quarter. How do you quantify the trade-off between having a once a night drug with high sodium versus twice a night drug with no sodium? Isn't having to wake up in the middle of night also unhealthy? And as a quick follow-up, do you have any views on reboxetine currently in Phase III/IV for narcolepsy with data expected in the fourth quarter?

恭喜本季度。您如何量化每晚一次高鈉藥物與每晚兩次無鈉藥物之間的權衡？半夜起床不是也不健康嗎？作為快速跟進，您對目前處於 III/IV 期治療發作性睡病的瑞波西汀（預計第四季度數據）有何看法？

Yes. Rob, maybe I could have you jump in a little bit on the nighttime impact of oxybate therapy?

是的。羅布，也許我可以讓你談談羥丁療法對夜間的影響？

Yes, happy to, Bruce. So we know that narcolepsy patients have significantly disrupted nighttime sleep. We also know that oxybate have a very big impact in improving the architecture of nighttime sleep. And we think that's why for a short-acting drug, patients then have substantial improvement in daytime symptoms like cataplexy or excessive daytime sleepiness. When you look across studies of oxybate, whether that be a fixed-dose high-sodium version or immediate release oxybate, there is improvement. It's very comparable. There's no evidence that a fixed-dose regimen improves the nighttime sleep to a greater extent. Patients typically do not normalize their sleep and there's really no evidence that waking to take a second administration impacts one way or another.

是的，很高興，布魯斯。所以我們知道發作性睡病患者的夜間睡眠受到了嚴重干擾。我們還知道，羥丁酸對於改善夜間睡眠結構具有非常大的影響。我們認為這就是為什麼對於短效藥物，患者的日間症狀（如猝倒或白天過度嗜睡）有顯著改善。當您查看羥丁酯的研究時，無論是固定劑量的高鈉版本還是立即釋放的羥丁酯，都會有所改善。非常具有可比性。沒有證據表明固定劑量療法可以更大程度地改善夜間睡眠。患者通常不會使他們的睡眠正常化，並且確實沒有證據表明醒來進行第二次給藥會產生這樣或那樣的影響。

And then Rob, I think there was a question on reboxetine at the end of the question as well.

然後羅布，我認為問題末尾也有一個關於瑞波西汀的問題。

And sorry, Bruce, could you just repeat that for me then?

抱歉，布魯斯，你能為我重複一遍嗎？

I think the question was any thoughts on data on reboxetine? I mean I'll just jump in and say historically, we -- in our conversations with KOLs, we've not found that there's as much interest in that as other drugs available or in development. This has been available in certain markets for a long time. in treatment of other diseases, but we haven't heard of a huge success in this patient population in the U.S.

我認為問題是對瑞波西汀的數據有什麼想法嗎？我的意思是，我想插話一下，從歷史上看，我們——在與 KOL 的對話中，我們沒有發現人們對此像其他可用或正在開發的藥物那樣感興趣。這在某些市場上已經存在很長時間了。治療其他疾病，但我們還沒有聽說在美國的這一患者群體中取得了巨大成功

Sure. Okay. Thanks for clarifying that, Bruce. And I would just say that our focus with Xywav is a nighttime administration to address the underlying cause of disruptive nighttime sleep, which has profound effects on daytime symptoms. Reboxetine is one of several drugs that's used as a daytime alerting agent, and is sometimes complementary to oxybate, but we don't think a substitute for many patients.

當然。好的。感謝您澄清這一點，布魯斯。我只想說，我們對 Xywav 的重點是夜間給藥，以解決夜間睡眠中斷的根本原因，這對白天的症狀有深遠的影響。瑞波西汀是用作日間警報劑的幾種藥物之一，有時可與羥丁酸互補，但我們認為它不能替代許多患者。

The next question comes from the line of Charles Duncan with Cantor Fitzgerald.

下一個問題來自查爾斯·鄧肯和坎托·菲茨杰拉德的關係。

Bruce and team, congrats on good commercial performance in the quarter. Sorry to ask about a nuance in the pipeline, but it actually relates to the next readout that could come. And that's on JZP150 and PTSD disorder. I guess I'm wondering if given that this is an early Phase II, would you focus more on stat sig and effect size or the overall results of the study to enable the drug to move forward. And then in terms of the statistical analysis plan, it looks like a wide range of doses. So I guess I'm wondering, is it each dose relative to placebo? Or would you combine doses, the analysis of the 2 dose groups versus placebo?

Bruce 和團隊祝賀本季度取得良好的商業業績。很抱歉詢問管道中的細微差別，但它實際上與可能出現的下一個讀數有關。這就是 JZP150 和 PTSD 障礙。我想我想知道，鑑於這是早期的第二階段，您是否會更多地關注統計數據和效應大小或研究的總體結果，以使藥物能夠向前發展。然後從統計分析計劃來看，劑量範圍看起來很廣。所以我想我想知道，每個劑量是否都相對於安慰劑？或者你會結合劑量，對 2 個劑量組與安慰劑進行分析？

Rob, do you want to take the 150 question?

Rob，你想回答 150 個問題嗎？

Yes. Thanks, Bruce. We do think the cap size is a comprehensive composite endpoint. It has regulatory endorsement as an endpoint that could be used for approval, and it does capture quite a bit the broad range of symptomatology in PTSD patients. So we do think that that's a good way to measure the effect of the drug. We are measuring other things in exploratory ways as well, which we certainly will take into account. You're right that the trial is 3 arms. There's 2 active dose levels and placebo. And given the sample size that we have, we feel we're well powered to make comparisons with both of those different dose levels against placebo. We don't have to collapse across those lines.

是的。謝謝，布魯斯。我們確實認為上限規模是一個綜合的綜合終點。它作為一個可用於批准的終點得到了監管機構的認可，並且它確實捕獲了 PTSD 患者的相當廣泛的症狀。所以我們確實認為這是衡量藥物效果的好方法。我們也在以探索性的方式衡量其他事情，我們當然會考慮到這一點。你說得對，審判是 3 個臂。有 2 個活性劑量水平和安慰劑。考慮到我們擁有的樣本量，我們認為我們有能力將這兩種不同劑量水平與安慰劑進行比較。我們不必越過這些界限而崩潰。

Well, I think that was our last question. So I just want to jump in and thank all of our questioners for moving us through, I think, most of our commercial business, a lot of our pipeline and our strategy. Hopefully, people feel great about the quarter on the top line, on the bottom line, the new guidance, increased diversification and the momentum we have in our business, particularly our 3 key growth drivers in Xywav, Epidiolex and Rylaze.

嗯，我想這是我們的最後一個問題。所以我想跳出來感謝所有提問者讓我們了解了我們的大部分商業業務、我們的很多管道和我們的戰略。希望人們對本季度的營收、利潤、新的指導、多元化的增加以及我們業務的勢頭感到滿意，特別是我們 Xywav、Epidiolex 和 Rylaze 的 3 個關鍵增長動力。

I'd just like to close today's call by recognizing all of our Jazz colleagues for their efforts in delivering new therapeutic options to patients, and thank our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

在結束今天的電話會議時，我想對所有 Jazz 同事為患者提供新的治療選擇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。

This concludes today's call. Thank you for your participation. You may now disconnect your lines.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開線路。