Harmony Biosciences Holdings Inc (HRMY) 2025 Q1 法說會逐字稿

(Operator Instructions)

（操作員指示）

Good morning. My name is Angela, and I will be your conference operator today. At this time, I would like to welcome everyone to Harmony Biosciences' first-quarter 2025 financial results conference call. (Operator Instructions)

早安.我叫安琪拉，今天我將擔任您的會議接線生。現在，我歡迎大家參加 Harmony Biosciences 2025 年第一季財務業績電話會議。（操作員指示）

Please be advised that today's conference may be recorded. (Operator Instructions)

請注意，今天的會議可能會被錄音。（操作員指示）

I will now turn the call over to Brennan Doyle, Head of Investor Relations. Please go ahead.

現在我將電話轉給投資者關係主管 Brennan Doyle。請繼續。

Thank you, operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences first-quarter 2025 financial results and provide a business update.

謝謝您，接線生。大家早安，感謝您今天加入我們，我們將回顧 Harmony Biosciences 2025 年第一季的財務業績並提供業務更新。

Before we start, I encourage everyone to go to the Investors section of our website to find the materials that accompany our discussion today, including the reconciliation of our GAAP to non-GAAP financial measures. At this stage of our life cycle, we believe that non-GAAP financial results better represent the underlying business performance.

在我們開始之前，我鼓勵大家造訪我們網站的「投資者」部分，尋找我們今天討論的資料，包括我們的 GAAP 與非 GAAP 財務指標的對帳。在我們生命週期的這個階段，我們相信非公認會計準則財務結果更能代表潛在的業務績效。

Our speakers today on the call are Dr. Jeffrey Dayno, President and CEO; Adam Zaeske, Chief Commercial Officer; Dr. Kumar Budur, Chief Medical and Scientific Officer; and Sandip Kapadia, Chief Financial Officer.

今天電話會議的發言人是總裁兼首席執行官 Jeffrey Dayno 博士、首席商務官 Adam Zaeske、首席醫療和科學官 Kumar Budur 博士和首席財務官 Sandip Kapadia。

As a reminder, we will be making forward-looking statements today which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties. Our actual results may differ materially, and we undertake no obligation to update these statements, even if circumstances change. We encourage you to consult the risk factors referenced in our SEC filings for additional details.

提醒一下，我們今天將根據我們目前的預期和信念做出前瞻性陳述。這些聲明受到一定風險和不確定性的影響。我們的實際結果可能存在重大差異，即使情況發生變化，我們也不承擔更新這些聲明的義務。我們鼓勵您查閱我們提交給美國證券交易委員會的文件中提到的風險因素以獲取更多詳細資訊。

I would now like to turn the call over to our CEO, Dr. Jeffrey Dayno. Jeff?

現在我想將電話轉給我們的執行長 Jeffrey Dayno 博士。傑夫？

Thank you, Brennan. Good morning, everyone, and thanks for joining our call today.

謝謝你，布倫南。大家早安，感謝大家今天參加我們的電話會議。

Before we get started, I am very excited to introduce and welcome Adam Zaeske, our new Chief Commercial Officer to the Harmony team. Adam will be sharing a bit about his background in a moment, but let me tell you, in just six weeks at Harmony, he has already made a big impact. He has been fully embraced by the team, shown himself to be a quick study and strategic thinker, and has brought fresh energy and focus as we continue to grow the Pitolisant franchise from the strong foundation we've built over the past five years.

在我們開始之前，我非常高興地介紹並歡迎我們的新任商務長 Adam Zaeske 加入 Harmony 團隊。亞當稍後會分享一些他的背景，但讓我告訴你，在 Harmony 工作的短短六週內，他已經產生了巨大的影響。他得到了團隊的充分認可，展現了快速學習和策略思考的能力，並為我們帶來了新的活力和焦點，讓我們能夠在過去五年建立的堅實基礎上繼續發展 Pitolisant 特許經營權。

Building off of our [four] years of profitability, Q1 was another strong quarter for Harmony. We continue to leverage our commercial success to drive both top- and bottom-line growth and are well positioned for significant momentum throughout 2025, fueled by key catalysts from a robust late-stage pipeline.

基於我們四年的獲利能力，第一季對 Harmony 來說又是一個強勁的季度。我們將繼續利用我們的商業成功來推動營收和利潤的成長，並在強大的後期管道等關鍵催化劑的推動下，為 2025 年全年的強勁成長勢頭做好準備。

Our next major clinical milestone is on track for the third quarter. The top-line data readout from the Phase 3 registrational trial of ZYN002 in patients with Fragile X syndrome, the RECONNECT study. A positive outcome could position us to deliver the first-ever, FDA-approved treatment for Fragile X syndrome, a significant milestone for patients and their families.

我們的下一個重要臨床里程碑預計將在第三季實現。ZYN002 針對脆性 X 症候群患者的 3 期註冊試驗 RECONNECT 研究的頂線資料讀數。如果結果積極，我們將能夠推出首個獲得 FDA 批准的脆性 X 綜合徵治療方法，這對患者及其家人來說是一個重要的里程碑。

I am very proud of the unique profile we have built at Harmony, a profitable, self-funding biotech company with a robust pipeline that has the potential to help hundreds of thousands of patients living with rare neurological diseases while creating durable, long-term value for our shareholders.

我為我們在 Harmony 建立的獨特形象感到非常自豪，這是一家盈利、自籌資金的生物技術公司，擁有強大的產品線，有可能幫助數十萬患有罕見神經系統疾病的患者，同時為我們的股東創造持久的長期價值。

First, a few comments on our core commercial business. WAKIX in narcolepsy continues to deliver strong, consistent growth. Net product revenue for the quarter was $184.7 million, a 20% increase year over year, now in its sixth year on the market. This growth reflects the highly differentiated product profile of WAKIX as the first and only FDA-approved, non-scheduled treatment for patients living with narcolepsy.

首先，就我們的核心商業業務發表幾點評論。WAKIX 在嗜睡症治療領域持續保持強勁、持續的成長動能。本季淨產品營收為 1.847 億美元，年增 20%，目前已是該產品上市第六年。這一增長反映了 WAKIX 作為首個也是唯一一個獲得 FDA 批准的針對嗜睡症患者的非計劃治療藥物的高度差異化產品特性。

Our unique commercial model and strong execution continue to deliver results. And we remain confident that WAKIX is on track to reach $1 billion-plus opportunity in narcolepsy alone, well ahead of its loss of exclusivity in 2030.

我們獨特的商業模式和強大的執行力繼續帶來成果。我們仍然相信，WAKIX 預計將在嗜睡症領域實現 10 億美元以上的市場機遇，遠早於 2030 年失去獨佔權的時期。

Turning to our pipeline where Harmony's story gets even more exciting. Over the last two years, we have been strategic in leveraging our strong balance sheet to build one of the most robust, late-stage pipelines in the industry for people living with rare neurological diseases.

轉向我們的管道，Harmony 的故事變得更加令人興奮。在過去的兩年裡，我們利用強大的資產負債表，為患有罕見神經系統疾病的人打造了業內最強大的後期研發管線之一。

Today we have three distinct franchises in sleep/wake, neurobehavioral disorders, and rare pediatric epilepsies, each with late-stage programs, each with plans to pursue multiple indications, and each one of these franchises with peak sales potential of $1 billion to $2 billion. Our pipeline now includes 8 assets across 13 development programs, and we expect to have up to 6 programs in Phase 3 trials by the end of this year.

如今，我們在睡眠/覺醒、神經行為障礙和罕見兒童癲癇領域擁有三個不同的特許經營權，每個特許經營權都有後期項目，每個特許經營權都有尋求多種適應症的計劃，每個特許經營權的峰值銷售潛力都達到 10 億至 20 億美元。我們的產品線目前包括 13 個開發項目中的 8 個資產，我們預計到今年年底將有多達 6 個項目進入第 3 階段試驗。

Some highlights from our pipeline. First, ZYN002, in patients living with Fragile X syndrome. The Phase 3 RECONNECT study is on track for top0line data in the third quarter. This trial is designed to replicate the positive findings from the pre-specified analysis on the primary outcome from the Phase 2/3 CONNECT study in the subgroup of patients with complete methylation of the FMR1 gene.

我們的管道的一些亮點。首先是 ZYN002，適用於患有脆性 X 症候群的患者。第三階段 RECONNECT 研究正在按計劃進行，並將於第三季公佈頂線數據。該試驗旨在複製 2/3 期 CONNECT 研究在 FMR1 基因完全甲基化患者亞組中對主要結果的預先指定分析的積極發現。

Next, Pitolisant HD, We are on track to initiate Phase 3 registrational trials in narcolepsy and idiopathic hypersomnia in the fourth quarter. Pitolisant HD is our next-generation, high-dose Pitolisant formulation with an enhanced PK profile designed to deliver greater efficacy with no change in the well-established safety tolerability profile of Pitolisant.

接下來，Pitilisant HD，我們預計在第四季度啟動針對發作性睡病和特發性嗜睡症的 3 期註冊試驗。Pitolisant HD 是我們新一代高劑量 Pitolisant 配方，具有增強的 PK 特性，旨在提供更高的療效，同時不改變 Pitolisant 完善的安全耐受性特性。

With utility patents filed out to 2044 and a target PDUFA date in 2028, Pitolisant HD provides us with a unique opportunity to extend and expand the Pitolisant franchise and pursue additional indications for which there are no approved treatments. Kumar will provide more color on our pipeline later in the call.

Pitolisant HD 的實用專利有效期至 2044 年，PDUFA 目標日期為 2028 年，它為我們提供了一個獨特的機會來延長和拓展 Pitolisant 特許經營權，並尋求尚未獲得批准的治療方法的其他適應症。庫馬爾稍後將在電話會議中提供有關我們管道的更多細節。

On the business development front, with over $600 million in cash and cash equivalents on the balance sheet, we are actively looking to further strengthen the pipeline. Our experienced business development team has a track record of discipline, smart execution, and we are focused on opportunities that can expand our leadership in sleep/wake, build out our neurobehavioral and epilepsy franchises, and/or bring in adjacent rare CNS assets. Our financial strength gives us flexibility, and we are well positioned to deploy our resources to further grow our pipeline and generate significant value for both patients and our shareholders.

在業務發展方面，資產負債表上有超過 6 億美元的現金和現金等價物，我們正在積極尋求進一步加強管道。我們經驗豐富的業務開發團隊擁有嚴謹的紀律和智慧執行的記錄，我們專注於能夠擴大我們在睡眠/覺醒領域的領導地位、建立我們的神經行為和癲癇特許經營權以及/或引入鄰近的稀有中樞神經系統資產的機會。我們的財務實力賦予我們靈活性，我們有能力部署資源，進一步擴大我們的產品線，為病患和股東創造巨大價值。

Against the current market backdrop, Harmony's profile is not only unique because of its profitability and strong cash generation, but Harmony is also well positioned to navigate the shifting geopolitical landscape, including the potential impact from proposed new tariffs. On the supply chain side, while our current manufacturing site for WAKIX is in France, we've been working on a secondary manufacturing site for WAKIX in the US and have made good progress toward bringing this site online.

在當前的市場背景下，Harmony 不僅因其盈利能力和強大的現金產生能力而獨樹一幟，而且還能夠很好地應對不斷變化的地緣政治格局，包括擬議的新關稅的潛在影響。在供應鏈方面，雖然我們目前為 WAKIX 設立的生產基地位於法國，但我們一直在美國為 WAKIX 設立第二個生產基地，並且在使該基地上線方面取得了良好的進展。

Looking ahead, Pitolisant HD is the future of the Pitolisant franchise with utility patents for HD extending out to 2044. The manufacturing of Pitolisant HD has been based in the US from the start of the program. Importantly, our exclusive licensing rights for WAKIX and the intellectual property associated with WAKIX , along with all the IP related to our pipeline products are domiciled here in the United States.

展望未來，Pitolisant HD 是 Pitolisant 特許經營的未來，其實用專利將延長至 2044 年。自計畫開始以來，Pitilisant HD 的製造就一直在美國進行。重要的是，我們對 WAKIX 的獨家許可權和與 WAKIX 相關的知識產權以及與我們的管道產品相關的所有知識產權均在美國境內。

I want to emphasize how unique Harmony's structure is compared to many others in the biotech industry because of its US-based operational foundation. While the outcome of many of these policy proposals is uncertain, we have taken proactive steps to ensure operational independence and minimize exposure to these potential risks.

我想強調的是，由於 Harmony 的營運基礎在美國，因此與生物技術行業的許多其他公司相比，其結構是多麼獨特。雖然許多政策建議的結果尚不確定，但我們已採取積極措施確保營運獨立性並盡量減少這些潛在風險。

In closing, I want to leave you with this. Harmony is a profitable, self-funding biotech company with a strong and growing commercial business. Next-generation formulations of Pitolisant on track for PDUFA dates in 2026 and 2028 with utility patents filed out to 2044 and a catalyst-rich, late-stage pipeline that is poised to deliver one or more new products or indication launches each year over the next several years with peak sales potential over $3 billion. If you look across our industry today, Harmony's profile stands out and offers a unique and compelling investment opportunity.

最後，我想告訴你們這一點。Harmony 是一家獲利良好、自籌資金的生物科技公司，擁有強勁且不斷成長的商業業務。Pitolisant 的下一代製劑預計在 2026 年和 2028 年獲得 PDUFA 批准，實用專利將於 2044 年提交，並且擁有富含催化劑的後期研發管線，預計在未來幾年內每年推出一款或多款新產品或適應症，峰值銷售潛力超過 30 億美元。如果您今天縱觀我們的行業，Harmony 的形象脫穎而出，並提供了獨特且引人注目的投資機會。

Thank you again for joining us today. I'll now turn the call over to Adam Zaeske, our Chief Commercial Officer, to share more about his background and provide an update on our commercial business. Welcome, Adam. We are thrilled to have you on the team.

再次感謝您今天加入我們。現在，我將把電話轉給我們的商務長 Adam Zaeske，讓他分享更多他的背景並提供我們商業業務的最新情況。歡迎光臨，亞當。我們很高興您能加入我們的團隊。

Thanks Jeff. I really appreciate the warm welcome from the entire Harmony Biosciences team, and I'm thrilled to be joining Harmony at such an exciting time. I've been very impressed with the clear focus on patients and what the team has achieved over the past several years with WAKIX.

謝謝傑夫。我非常感謝整個 Harmony Biosciences 團隊的熱烈歡迎，我很高興能在如此激動人心的時刻加入 Harmony。我對 WAKIX 團隊對患者的明確關注以及過去幾年來所取得的成就印象深刻。

I'm excited to continue that success for many years to come and to expand on that with the next-generation Pitolisant formulations as well as the late-stage products in the pipeline. I hope to leverage my experience having led marketing sales and market access teams for 10 years in the US as well as leading large and small country organizations in Europe for 10 years.

我很高興能夠在未來的許多年裡繼續保持這種成功，並透過下一代 Pitolisant 配方以及正在研發的後期產品來擴大這一成功。我希望利用我在美國領導行銷銷售和市場准入團隊 10 年以及在歐洲領導大小國家組織 10 年的經驗。

My most recent role was leading a region of 25 countries, nearly 900 employees, and over $2 billion in revenue, with double-digit growth for the past three consecutive years as the largest contributor to revenue and growth for Europe. Prior to that, I led the franchise teams for Europe across rare disease, neuroscience, immunology, hematology, oncology, gastroenterology, and plasma-derived therapy. I've been a part of building several multi-billion dollar brands, and I've worked on 10 rare disease launches in the past 10 years.

我最近的職位是領導一個涵蓋 25 個國家、近 900 名員工、收入超過 20 億美元的地區，過去三年連續實現兩位數成長，成為歐洲收入和成長的最大貢獻者。在此之前，我領導了歐洲特許經營團隊，涉及罕見疾病、神經科學、免疫學、血液學、腫瘤學、胃腸病學和血漿衍生療法。我參與打造了多個價值數十億美元的品牌，並在過去 10 年中參與了 10 種罕見疾病藥物的上市。

Turning to Harmony's performance, Q1 2025 demonstrated the ongoing strength of our core business and our ability to deliver durable growth. Notably, we achieved $184.7 million in net sales, and the fundamentals of the business remain strong and stable.

談到 Harmony 的業績，2025 年第一季證明了我們核心業務的持續實力和實現持久成長的能力。值得注意的是，我們的淨銷售額達到了 1.847 億美元，業務基本面仍然強勁而穩定。

In the first quarter, we saw the familiar seasonal rhythm to our performance consistent with prior years. This include the traditional Q1 challenges faced across the industry related to payer dynamics, followed by positive momentum and increased prescription demand coming out of Q1. The continued strong 20% year-over-year first-quarter growth in WAKIX's net revenue, now in its sixth year post-launch, underscores the sustained high demand for WAKIX within the narcolepsy market driven by the broad clinical utility of WAKIX and the fact that it is the first and only non-scheduled treatment for patients with narcolepsy.

在第一季度，我們看到了與往年一致的熟悉的季節性節奏。這包括整個行業面臨的與付款人動態相關的傳統 Q1 挑戰，以及 Q1 帶來的積極勢頭和處方需求的增加。WAKIX 上市六年以來，其淨收入第一季度繼續保持 20% 的強勁同比增長，凸顯了發作性睡病市場對 WAKIX 的持續高需求，這得益於 WAKIX 廣泛的臨床實用性以及它是首個也是唯一一個針對發作性睡病患者的非計劃治療方法。

This differentiated profile allows us to tap into the full potential of the approximately 80,000 diagnosed narcolepsy patients. Even with the introduction of new and generic oxybate alternatives, we continue to see consistent utilization of WAKIX among the approximately 4,000 HCPs enrolled in oxybate REMs.

這種差異化的特徵使我們能夠充分挖掘大約 80,000 名確診嗜睡症患者的潛力。即使推出了新的和通用的羥基丁酸鹽替代品，我們仍然看到在參加羥基丁酸鹽 REM 的約 4,000 名 HCP 中持續使用 WAKIX。

Despite our high penetration within this group, WAKIX prescriptions for additional narcolepsy patients within this segment continues to grow each quarter. We're pleased with the robust growth in WAKIX prescribers beyond those enrolled in oxybate REMs, demonstrating WAKIX's ongoing success in capturing a broader segment of branded prescribers. Additionally, we have now reached over 50% penetration within this approximately 5,000 HCP segment as of the end of Q1.

儘管我們在該群體中的滲透率很高，但針對該細分市場中更多嗜睡症患者的 WAKIX 處方量每個季度仍在持續增長。我們很高興看到 WAKIX 處方人員的數量在除參加羥基丁酸鹽 REM 的處方人員之外也呈現強勁增長，這表明 WAKIX 在吸引更廣泛的品牌處方人員方面取得了持續成功。此外，截至第一季末，我們在約 5,000 名 HCP 細分市場中的滲透率已超過 50%。

As we look ahead to full year 2025, we're confident in the strength of the underlying business fundamentals and optimistic that they will fuel continued growth of WAKIX. Based on this, we confirm our net revenue guidance in the range of $820 million to $860 million, and we remain on track to achieve $1 billion-plus in narcolepsy alone.

展望 2025 年全年，我們對基礎業務基本面的強勁充滿信心，並樂觀地認為它們將推動 WAKIX 的持續成長。基於此，我們確認淨收入預期在 8.2 億美元至 8.6 億美元之間，並且我們仍有望僅在嗜睡症領域就實現 10 億美元以上的收入。

Leveraging our robust, scalable commercial infrastructure, we're well positioned to unlock significant longer-term growth and value with our next-generation Pitolisant programs. Our development of both Pitolisant gastro-resistant, the GR, and high-dose, HD, formulations is centered on unmet patient needs, aiming to deliver meaningful improvements in care and extend the growth and revenue of the Pitolisant franchise into the mid-2040s.

利用我們強大、可擴展的商業基礎設施，我們有能力透過下一代 Pitolisant 計劃實現顯著的長期成長和價值。我們開發的 Pitolisant 腸溶片 (GR) 和高劑量 (HD) 製劑均以未滿足的患者需求為中心，旨在提供有意義的護理改進，並將 Pitolisant 特許經營的增長和收入延長至 2040 年代中期。

Kumar will elaborate on the specifics of the HD and GR development programs. Initial market research among HCPs and payers regarding the HD target product profile has demonstrated strong interest from both physicians and payers and clear unmet need for patients.

庫馬爾將詳細介紹 HD 和 GR 發展計劃的具體內容。針對亨廷頓氏病目標產品概況，在 HCP 和付款人中進行的初步市場研究表明，醫生和付款人都表現出濃厚的興趣，並且患者的需求明顯尚未得到滿足。

In summary, we saw continued strong growth of WAKIX in Q1. Our patient-centric drug development approach to the Pitolisant life cycle management program combined with our unique commercial model will ensure durable growth through the mid-2040s.

總而言之，我們看到 WAKIX 在第一季繼續保持強勁成長。我們以患者為中心的藥物開發方法，結合 Pitolisant 生命週期管理計劃，加上我們獨特的商業模式，將確保到 2040 年代中期實現持久增長。

And in closing, my experiences in both rare disease and neurology were tremendously rewarding parts of my career. I'm excited to return to these therapeutic areas and contribute to Harmony's potential to help many more patients living with unmet medical needs.

最後，我在罕見疾病和神經病學方面的經驗是我職業生涯中非常有價值的部分。我很高興能夠重返這些治療領域，為 Harmony 的潛力做出貢獻，幫助更多醫療需求未被滿足的患者。

I would now like to turn the call over to our Chief Medical and Scientific Officer, Kumar Budur, to discuss the advancements in our clinical development programs. Kumar?

現在，我想將電話轉給我們的首席醫療和科學官 Kumar Budur，討論我們臨床開發計劃的進展。庫馬爾？

Thank you, Adam. Good morning, everyone, and thank you for joining us today. In R&D, we continue to make progress in advancing our pipeline across 13 development programs, 8 different assets, and 3 distinct franchises focused on rare neurological diseases with high unmet medical needs.

謝謝你，亞當。大家早安，感謝大家今天加入我們。在研發方面，我們繼續在 13 個開發項目、8 種不同資產和 3 個不同特許經營權方面取得進展，重點關注醫療需求尚未滿足的罕見神經系統疾病。

We have four Phase 3 registrational trials ongoing in four distinct indications, and we will have up to six Phase 3 registration files by the end of this year. This makes our portfolio one of the most robust late-stage pipelines in the industry with the potential to deliver one or more new products or indication launches every year in the coming years.

我們目前正在針對四種不同的適應症進行四項 3 期註冊試驗，到今年年底，我們將擁有多達六個 3 期註冊文件。這使得我們的產品組合成為業內最強大的後期產品線之一，並有可能在未來幾年每年推出一款或多款新產品或適應症。

Our full clinical development pipeline is shown on slide number 5. And the clinical development highlights are on slide 6 through slide 11.

我們的完整臨床開發流程顯示在投影片 5 上。臨床開發亮點在第 6 張至第 11 張投影片。

Let's begin with our sleep/wake franchise. Our next-gen Pitolisant programs, which are patient-centric development programs, are aimed to build upon the product profile of Pitolisant. We are on track to initiate a Phase 3 registration trial of Pitolisant HD in narcolepsy in Q4 2025 with a target PDUFA for date in 2028.

讓我們從睡眠/覺醒特許經營開始。我們的下一代 Pitolisant 項目是以患者為中心的開發項目，旨在以 Pitolisant 的產品形象為基礎。我們計劃於 2025 年第四季啟動 Pitolisant HD 治療嗜睡症的 3 期註冊試驗，目標 PDUFA 日期為 2028 年。

This optimized higher-dose formulation holds the promise of greater efficacy in addressing excessive daytime sleepiness, the most important unmet need in patients with narcolepsy, and also target fatigue, a symptom experienced by about 60% to 70% of patients with narcolepsy, for which there are no currently approved treatments. We are also on track to initiate our Phase 3 registration trial in idiopathic hypersomnia in Q4 2025.

這種優化的高劑量配方有望更有效地解決白天過度嗜睡問題（嗜睡症患者最重要的未滿足需求），並針對疲勞問題（約 60% 至 70% 的嗜睡症患者都會經歷這種症狀，目前尚無批准的治療方法）。我們也計劃於 2025 年第四季啟動特發性嗜睡症的 3 期註冊試驗。

Pitolisant HD is expected to deliver efficacy in excessive daytime sleepiness and also address critical symptoms such as sleep inertia, another core symptom in patients with idiopathic hypersomnia for which there are no approved treatments. This double-blind, randomized placebo controlled parallel arms study is designed with FDA input, and we anticipate a PDUFA date in 2028.

Pitolisant HD 有望有效治療白天過度嗜睡症，並能解決睡眠慣性等關鍵症狀，睡眠慣性是特發性嗜睡症患者的另一個核心症狀，目前尚無批准的治療方法。這項雙盲、隨機安慰劑對照平行組研究是根據 FDA 的意見設計的，我們預期 PDUFA 日期為 2028 年。

Moving on to our Pitolisant GR program, this formulation is designed to adjust the GI comorbidity prevalent in almost 80% of patients with narcolepsy and also designed to give patients an ability to start at the therapeutic dose range with no titration. We initiated the pivotal BE study in Q1 2025, and the top-line data are anticipated in Q3 2025 with the projected PDUFA date in 2026. Utility patents have been submitted for both Pitolisant GR and Pitolisant HD with the potential for patent protection until 2044.

繼續我們的 Pitolisant GR 計劃，該配方旨在調整近 80% 嗜睡症患者普遍存在的胃腸道合併症，同時也旨在讓患者能夠從治療劑量範圍開始，無需滴定。我們於 2025 年第一季啟動了關鍵的 BE 研究，預計在 2025 年第三季獲得頂線數據，預計 PDUFA 日期為 2026 年。Pitolisant GR 和 Pitolisant HD 均已提交實用專利，專利保護期限可能至 2044 年。

Next in our sleep/wake franchise is our orexin receptor agonist program, BP1.5205, a potential best-in-class candidate currently in pre-clinical development. In vitro pharmacology data demonstrate greater potency compared to all other publicly disclosed orexin-2 agonists.

我們的睡眠/覺醒系列的下一個產品是食慾素受體激動劑計畫 BP1.5205，它是目前處於臨床前開發階段的潛在最佳候選藥物。體外藥理學數據顯示，與所有其他公開揭露的食慾素-2激動劑相比，其效力更強。

The combination of high potency, excellent selectivity, potential for one's daily dosing, and robust pre-clinical safety data underscores its best-in-class potential. We will be presenting a comprehensive pre-clinical safety and efficacy data at the upcoming annual sleep meeting in June, and the data will demonstrate efficacy in sleepiness consistent with its high potency. We remain on track to find an IMPD by mid-2025 with first in-human studies in the second half of this year and anticipate to share clinical data in 2026.

高效力、優異的選擇性、每日服用的潛力以及強大的臨床前安全數據的結合凸顯了其一流的潛力。我們將在即將於 6 月召開的年度睡眠會議上展示全面的臨床前安全性和有效性數據，這些數據將證明其在嗜睡方面的有效性與其高效力相一致。我們仍有望在 2025 年中期找到 IMPD，並在今年下半年進行首次人體研究，並預計在 2026 年分享臨床數據。

Moving on, I'm very excited about our neurobehavioral franchise, which is the next major catalyst in our portfolio. The top-end data from the ZYN002 Phase 3 registration trial, the RECONNECT study in Fragile X syndrome is in the third quarter of this year.

繼續，我對我們的神經行為特許經營感到非常興奮，這是我們投資組合中的下一個主要催化劑。ZYN002 第 3 階段註冊試驗的最高端數據，即脆性 X 症候群的 RECONNECT 研究將在今年第三季公佈。

Fragile X syndrome, a rare genetic disorder caused by mutation of the FMR1 gene on the X chromosome, results in decreased or no FMR protein production, especially in patients with complete methylation that results in silencing of the gene. Lack of FMR protein causes endocannabinoid defibrillation, leading to significant neurobehavioral symptoms, intellectual impairment, developmental delays, and other symptoms. In fact, Fragile X syndrome is the most common known inherited cause of intellectual impairment and autism spectrum disorders, with an estimated prevalence of approximately 80,000 patients each in the US and the EU.

脆性 X 症候群是一種由 X 染色體上的 FMR1 基因突變引起的罕見遺傳性疾病，會導致 FMR 蛋白質生成減少或不生成，尤其是在基因完全甲基化導致沉默的患者中。缺乏FMR蛋白會導致內源性大麻素去顫，進而導致嚴重的神經行為症狀、智能障礙、發育遲緩等症狀。事實上，脆性 X 症候群是已知的最常見的智力障礙和自閉症譜系障礙的遺傳病因，據估計，美國和歐盟各有約 80,000 名患者。

ZYN002 represents a normal therapeutic approach. It's a 100% synthetic cannabidiol devoid of THC in a patent-protected, permeation-enhanced transdermal gel, delivering the drug directly into the systemic circulation. ZYN002 is designed to modulate the endocannabinoid system by interacting with CD1 receptors, aiming to restore endocannabinoid homeostasis and thereby, alleviating the neurobehavioral symptoms.

ZYN002代表一種正常的治療方法。它是一種 100% 合成的大麻二酚，不含 THC，採用受專利保護的、滲透性增強的透皮凝膠，可將藥物直接輸送到全身循環中。ZYN002 旨在透過與 CD1 受體相互作用來調節內源性大麻素系統，旨在恢復內源性大麻素穩態，從而緩解神經行為症狀。

Notably, transdermal administration of ZYN002 offers a significant advantage in tolerability and safety compared to oral cannabidiol, which is associated with substantial gastrointestinal disturbances such as nausea, vomiting, abdominal cramps, and diarrhea. By avoiding the [first pass] hepatic metabolism, ZYN002 is not associated with liver function abnormalities that are often observed with oral cannabidiol.

值得注意的是，與口服大麻二酚相比，ZYN002 的透皮給藥在耐受性和安全性方面具有顯著優勢，而口服大麻二酚會引起嚴重的胃腸道不適，如噁心、嘔吐、腹部絞痛和腹瀉。透過避免[首過]肝臟代謝，ZYN002 不會出現口服大麻二酚時常出現的肝功能異常。

The ongoing Phase 3 registrational trial, the RECONNECT study, builds upon the data and insights from the last Phase 2/3 CONNECT study. The RECONNECT study essentially seeks to replicate the clinically meaningful and statistically significant efficacy signals observing patients with complete methylation in the CONNECT study.

正在進行的 3 期註冊試驗 RECONNECT 研究以上一期 2/3 期 CONNECT 研究的數據和見解為基礎。RECONNECT 研究本質上尋求複製 CONNECT 研究中觀察完全甲基化患者的具有臨床意義和統計學意義的療效訊號。

We have completed recruitment and closed new patient screenings. We are on track for top-line data in Q3 2025. If positive, the RECONNECT study is expected to support regulatory approvals in both US and EU, and Harmony holds global rights for ZYN002.

我們已經完成招募並結束了新患者篩選。我們預計在 2025 年第三季實現營收數據。如果結果呈陽性，RECONNECT 研究預計將獲得美國和歐盟的監管部門批准，而 Harmony 則擁有 ZYN002 的全球權利。

Based on the etiology and pathophysiology of Fragile X syndrome, ZYN002mechanism of action, the robust clinical data in patients with complete methylation from the CONNECT study, as well as the enhancements in the design of the RECONNECT study based on the learning from the study, we have a strong conviction in the program's success. If approved, ZYN002 will be the first and only treatment approved for any symptoms in patients with Fragile X syndrome.

基於脆性X症候群的病因和病理生理、ZYN002的作用機制、CONNECT研究中完全甲基化患者的可靠臨床數據，以及基於該研究經驗教訓對RECONNECT研究設計的改進，我們對該計劃的成功充滿信心。如果獲得批准，ZYN002 將成為第一個也是唯一一個核准用於治療脆性 X 症候群患者症狀的藥物。

Furthermore, we remain on schedule to initiate a Phase 3 registration trial in 22q deletion syndrome in 2025. This rare disorder with significant neurobehavioral symptoms and no approved therapies affects approximately 80,000 individuals each in the US and Europe.

此外，我們仍按計畫於 2025 年啟動 22q 缺失症候群的 3 期註冊試驗。這種罕見疾病有明顯的神經行為症狀，且尚無核准的治療方法，美國和歐洲各有約 8 萬人受到影響。

Finally, a few words on our epilepsy franchise where we have the most advanced 5-HT2 serotonin development programs in developmental and epileptic encephalopathies. EPX-100, clemizole hydrochloride program, is actively enrolling participants in the global Phase 3 registration of trials, the ARGUS study in Dravet syndrome and the LIGHTHOUSE study in Lennox-Gastaut syndrome. Our other investigational product in developmental and epileptic encephalopathies, EPX-200, a liquid formulation of lorcaserin, is in the pre-IND phase.

最後，簡單介紹一下我們的癲癇治療專營權，我們在發育性和癲癇性腦病方面擁有最先進的 5-HT2 血清素開發計劃。EPX-100，鹽酸克立咪唑項目，正在積極招募參與者參與全球 3 期註冊試驗、Dravet 綜合徵的 ARGUS 研究和 Lennox-Gastaut 綜合徵的 LIGHTHOUSE 研究。我們在發育性和癲癇性腦病變領域的另一種研究產品是 EPX-200，一種氯卡色林的液體製劑，目前正處於 IND 前階段。

In conclusion, we are making strong progress across our late-stage rare neuro portfolio with the potential to launch one or more new products or indications each year in the coming years. More importantly, this progress holds the promise of providing meaningful new treatment options to hundreds of thousands of individuals affected by rare neurological disorders. For many of these patients, there are currently no approved treatments, but the existing therapies offer limited efficacy and considerable safety and tolerability issues.

總而言之，我們在後期罕見神經疾病產品組合方面取得了長足的進步，並有可能在未來幾年每年推出一款或多款新產品或適應症。更重要的是，這項進展有望為數十萬患有罕見神經系統疾病的患者提供有意義的新治療選擇。對於許多此類患者，目前尚無核准的治療方法，但現有療法的療效有限，且存在相當大的安全性和耐受性問題。

As always, on behalf of Harmony, I would like to thank all the patients and their families who are participating in our clinical trials as well as our clinical investigators and site personnel for their efforts and commitment in helping us to advance our development programs.

像往常一樣，我謹代表 Harmony 感謝所有參與我們臨床試驗的患者及其家人，以及我們的臨床研究人員和現場人員，感謝他們為幫助我們推進開發計劃所做的努力和承諾。

I'll now turn the call over to our CFO, Sandip Kapadia, for an update on our financial performance. Sandip?

現在，我將把電話轉給我們的財務長桑迪普·卡帕迪亞 (Sandip Kapadia)，以了解我們的財務表現。桑迪普？

Thank you, Kumar, and good morning, everyone. This morning we issued our first quarter of 2025 earnings release and filed our 10-Q, where you'll find the details of our financial and operating results. Our financial performance is also shown on slides 12 through 14.

謝謝你，庫馬爾，大家早安。今天上午，我們發布了 2025 年第一季的收益報告並提交了 10-Q，您可以在其中找到我們的財務和經營業績的詳細資訊。我們的財務表現也展示在第 12 至 14 張投影片。

We're off to a great start to the year in 2025. We reported another quarter for strong growth in revenues of 20% and net income growth of 19%, along with closing the quarter with over $600 million of cash, cash equivalents, and investments on the balance sheet.

2025 年我們迎來了一個好的開始。我們報告稱，本季營收強勁成長 20%，淨收入成長 19%，同時本季末資產負債表上的現金、現金等價物和投資超過 6 億美元。

We continue to have a very unique profile in biotech, with growing top line, profitability, and generating positive cash flow. As a result, we are well positioned to advance our growth strategy and look for opportunities to drive incremental value for shareholders.

我們在生技領域繼續保持著非常獨特的地位，營業收入和獲利能力不斷增長，並產生了正現金流。因此，我們已做好準備，推進我們的成長策略，並尋找機會為股東創造增量價值。

For the first quarter of 2025, we reported net revenues of $184.7 million compared to $154.6 million in the prior-year quarter, representing a growth of 20%. Performance in the quarter reflects the strong underlying demand for WAKIX coupled with the typical seasonal dynamics in Q1 that the industry as a whole experiences, including higher growth [than] net deductions, while not seeing a significant change in trade inventories.

2025 年第一季度，我們的淨收入為 1.847 億美元，而去年同期為 1.546 億美元，成長了 20%。本季的業績反映了 WAKIX 強勁的潛在需求，以及整個行業在第一季經歷的典型季節性動態，包括成長率高於淨扣除額，同時貿易庫存沒有顯著變化。

We've reported total operating expenses for the first quarter of $96.6 million compared to $75.1 million for the same quarter in 2024. Growth in our expenses were driven by our expanding late-stage pipeline along with investments for the commercialization of WAKIX in narcolepsy.

我們報告的第一季總營運費用為 9,660 萬美元，而 2024 年同期為 7,510 萬美元。我們的支出成長是由我們不斷擴大的後期產品線以及對 WAKIX 在嗜睡症治療中的商業化投資所推動的。

We also reported solid net income and margins. Non-GAAP adjusted net income for the first quarter of 2025 was $60.4 million or $1.03 per diluted share compared to $50.7 million or $0.88 per diluted share in the prior-year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance. Please see our press release for a reconciliation of GAAP to non-GAAP results.

我們也報告了穩健的淨收入和利潤率。2025 年第一季非公認會計準則調整後淨收入為 6,040 萬美元，即每股攤薄收益 1.03 美元，而去年同期為 5,070 萬美元，即每股攤薄收益 0.88 美元。我們認為非公認會計準則調整後的淨收入能更能反映基礎業務表現。請參閱我們的新聞稿，以了解 GAAP 與非 GAAP 結果的對帳。

We also ended the first quarter with $610.2 million in cash, cash equivalents, and investments on the balance sheet.

第一季末，我們的資產負債表上還有 6.102 億美元的現金、現金等價物和投資。

And looking ahead to the balance of 2025, we are reiterating our net revenue guidance for 2025 of $820 million to $860 million, highlighting our progress towards a $1 billion-plus opportunity in narcolepsy alone. We expect continued strong quarter-over-quarter growth while noting the potential of trade inventory drawdown of a few days in Q2 as we head into the summer months.

展望 2025 年餘下時間，我們重申 2025 年淨收入預期為 8.2 億至 8.6 億美元，凸顯我們在嗜睡症領域取得的 10 億美元以上的機會進展。我們預計季度環比成長將繼續強勁，但同時注意到，隨著進入夏季，第二季貿易庫存可能會減少幾天。

With respect to expenses, we expect increased R&D investments as we advance our late-stage pipeline with multiple programs in Phase 3 registrational trials. As previously noted, we expect to potentially incur $29 million in R&D-related milestone payments in 2025, including milestones for the completion of the Phase 3 trial for ZYN002 in Fragile X syndrome, along with a milestone for positive top-line data from this trial. In addition, there is a milestone related to the initiation of the Phase 1 trial in our orexin-2 agonist program, which we anticipate in the second half of this year.

在費用方面，隨著我們透過第三階段註冊試驗中的多個項目推進後期研發管線，我們預計研發投資將會增加。如前所述，我們預計 2025 年可能產生 2,900 萬美元的研發相關里程碑付款，包括完成 ZYN002 治療脆性 X 症候群的 3 期試驗的里程碑，以及該試驗獲得積極的頂線數據的里程碑。此外，我們的食慾素-2激動劑計畫的第一階段試驗的啟動也具有里程碑意義，我們預計該試驗將在今年下半年進行。

In summary, I'm pleased with the great start we're off to in 2025. We once again delivered a quarter with double-digit, top-line growth and healthy operating margins. This, along with our US operational footprints, positions as well as we move through the year with the potential for significant value creation through our catalyst for pipeline.

總而言之，我對我們在 2025 年取得的良好開端感到高興。本季度，我們再次實現了兩位數的營收成長和健康的營業利潤率。這一點，加上我們在美國的業務足跡、地位以及我們全年透過管道催化劑創造重大價值的潛力。

And with that, I'd like to turn the call back over to Jeff for his closing remarks. Jeff?

最後，我想將電話轉回給傑夫，請他做最後發言。傑夫？

Thank you, Sandip. To wrap up, Harmony Biosciences offers a very compelling profile, a strong commercial foundational business generating significant cash and profitability, a robust late-stage pipeline with meaningful near-term catalysts poised to deliver one or more new product or indication launches each year over the next several years and peak sales potential over $3 billion, over $600 million on the balance sheet funding the entire enterprise, giving us the capacity to build out our pipeline further and create even greater value potential.

謝謝你，桑迪普。總而言之，Harmony Biosciences 提供了非常引人注目的形象，強大的商業基礎業務產生了大量現金和盈利能力，強大的後期管道具有有意義的短期催化劑，準備在未來幾年每年推出一款或多款新產品或適應症，峰值銷售潛力超過 30 億美元，資產負債表上有超過 6 億美元的資金為整個企業提供資金，使我們能夠進一步的價值管道。

I am proud of the entire team and what we've accomplished together, transforming Harmony into a high-growth biotech company, delivering on our promise to patients and creating durable long-term value for our shareholders.

我為整個團隊以及我們共同取得的成就感到自豪，將 Harmony 轉變為高成長生物技術公司，兌現了對患者的承諾，並為我們的股東創造了持久的長期價值。

So thank you. And I will now turn the call back over to the operator. Operator?

所以謝謝你。現在我將把電話轉回給接線生。操作員？

Thank you. (Operator Instructions)

謝謝。（操作員指示）

Graig Suvannavejh, Mizuho Securities.

Graig Suvannavejh，瑞穗證券。

Hey. Thank you very much for taking my question. Congrats on the quarter. Two questions, please. First, just on the pipeline and for ZYN002, could you please remind us what the powering assumptions are for the study and also what perhaps risk mitigation strategies and what strategies for optimizing clinical trial success you've put in place. That's my first question.

嘿。非常感謝您回答我的問題。恭喜本季取得佳績。請問兩個問題。首先，僅就管道和 ZYN002 而言，您能否提醒我們該研究的驅動假設是什麼，以及您可能採取的風險緩解策略和優化臨床試驗成功的策略是什麼。這是我的第一個問題。

Then my second question is just for Adam. Congrats on the new role as Chief Commercial Officer, but could you please share with us maybe what you've seen thus far with the commercial team and strategies that are in place supporting WAKIX? And are there any changes or tweaks that you think, given your experience, can be put in place? Thanks so much.

我的第二個問題是針對亞當的。恭喜您擔任首席商務官的新職務，但您能否與我們分享一下您迄今為止對商業團隊的了解以及支持 WAKIX 的策略？根據您的經驗，您認為可以進行哪些改變或調整？非常感謝。

Yeah. Good morning, Graig. Thank you for your questions. First to Kumar on ZYN002. Very excited for that opportunity, and Kumar can share with you the powering and how that program is designed and our conviction in the top-line data that's on track for Q3. Kumar?

是的。早安，格雷格。感謝您的提問。首先是 ZYN002 上的 Kumar。我對這個機會感到非常興奮，Kumar 可以與您分享該計劃的動力和設計方式，以及我們對第三季收入數據的信心。庫馬爾？

Hey. Good morning, Graig. Thanks for the question. Regarding the powering of the study, the study is powered more than 90% for the primary endpoint, which is change in the social avoidance severity from baseline to the end of the study as measured by Aberrant Behavior Checklist - Community Edition specific for Fragile X syndrome, and the study powering, and the sample size calculation, and all the statistical analysis was planned based on the learning from the CONNECT study, where as we have disclosed in the past, we not just saw a clinically meaningful but also a nominally, statistically significant difference in patients with complete methylation on the same primary endpoint.

嘿。早安，格雷格。謝謝你的提問。關於研究的動力，該研究對主要終點的動力超過 90%，即從基線到研究結束的社交迴避嚴重程度的變化，以針對脆性 X 綜合徵的異常行為檢查表 - 社區版進行測量，並且研究動力和样本量計算以及所有統計分析都是基於 CONNECT 研究的經驗進行規劃的，正如我們過去所披露的那樣，我們不僅看到了同一片上的主要意義。

Regarding the question on the checks and balances within the clinical trial, Graig, as you know, many of us have done so many neuropsychiatric clinical trials, and these clinical trials are very unique. It's very important to make sure that the right patients get into the study, and we have ensured it in a way with Fragile X syndrome, it makes it somewhat easier because all of these patients need to have full methylation -- full mutation. That is confirmed by looking at the CGG repeats and also full complete methylation via PCR test.

關於臨床試驗內部製衡的問題，格雷格，如你所知，我們很多人都做過很多神經精神病學臨床試驗，這些臨床試驗非常獨特。確保合適的患者參與研究非常重要，我們已經透過脆性 X 症候群確保了這一點，這使得研究變得更容易一些，因為所有這些患者都需要有完全甲基化 - 完全突變。透過 PCR 測試觀察 CGG 重複和完整甲基化可以證實這一點。

And after that, we have put up pretty rigorous criteria and checks and balances in place to make sure that the baseline severity meets the criteria that we have set. And also, the caregivers are trained extensively via an independent third-party vendor whenever they complete the assessment.

此後，我們制定了非常嚴格的標準和製衡措施，以確保基準嚴重程度符合我們設定的標準。此外，護理人員在完成評估後都會透過獨立的第三方供應商接受廣泛的培訓。

So overall lots of checks and balances in place. Again, as we mentioned in the past, this study is designed based on the learnings from the CONNECT study. Not only that, we made several enhancements in the RECONNECT study to increase the probability of success. Overall, very high level of conviction and confidence in potentially bringing the first treatment for any symptoms in patients with Fragile X syndrome.

因此總體而言，存在著許多製衡措施。再次，正如我們過去提到的，這項研究是根據 CONNECT 研究的經驗設計的。不僅如此，我們還在 RECONNECT 研究中做出了多項改進，以增加成功的機率。整體而言，我們堅信並有信心為脆性 X 症候群患者帶來首個任何症狀的治療方法。

Thank you, Kumar. And over to Adam for his initial impressions, and let me reiterate our welcome to Adam to the Harmony team. Adam?

謝謝你，庫馬爾。接下來請聽聽 Adam 的初步印象，讓我再次歡迎 Adam 加入 Harmony 團隊。亞當？

Thank you Jeff, and thank you, Graig, for the question. Look, it's fantastic to be part of the team here at Harmony now. I'm super excited. I've been thrilled with what I've seen so far.

謝謝傑夫，也謝謝格雷格提出的問題。瞧，現在成為 Harmony 團隊的一員真是太棒了。我超興奮。我對目前所見的一切感到非常興奮。

I was originally attracted to Harmony Biosciences for a couple of reasons. I saw an organization that had a very clear purpose and a shared purpose around really trying to benefit patients and meet unmet needs of those patients in neurology. I saw an extremely strong team, a lot of talented individuals.

我最初被 Harmony Biosciences 吸引有幾個原因。我看到一個組織，它有一個非常明確的目標和共同的目標，即真正努力造福患者並滿足神經病學患者未滿足的需求。我看到了一支非常強大的團隊，有很多才華橫溢的個人。

And I think as you've seen here today, the outstanding performance, and it just continues quarter over quarter, year over year, in addition to having a really exciting pipeline, a pipeline that is developed with a very clear patient orientation. And it's, I think, smartly designed to really meet the remaining unmet needs of patients in each of these areas.

我認為，正如大家今天所看到的，我們擁有出色的表現，並且這一表現逐季、逐年持續，此外，我們還擁有真正令人興奮的產品線，這些產品線的開發都非常明確地以患者為導向。我認為，它的設計非常巧妙，能夠真正滿足各領域患者尚未滿足的需求。

So I'm just about one month in. I've had a wonderful opportunity to connect with the team, and really, I'm focused on learning and listening at this stage. My platform is pretty simple. I'm focused on how do we continue the strong performance that the organization has delivered for the past five-plus years consistently, and how do we prepare for the future.

所以我才剛一個月。我有一個非常好的機會與團隊建立聯繫，事實上，我在這個階段專注於學習和傾聽。我的平台非常簡單。我關注的是我們如何延續該組織過去五年多來持續表現的強勁勢頭，以及我們如何為未來做好準備。

I think the team has a lot of great ideas, and I'm really enjoying the discussion. We're going to be evaluating tweaks, as you say, tweaks and opportunities moving forward and prioritize those. And I'm confident we will continue the strong performance with WAKIX, and we will be prepared for the future with the exciting pipeline that exists here. So thank you for your question.

我認為團隊有很多很棒的想法，我真的很享受討論。正如您所說，我們將評估調整、未來的調整和機會，並確定其優先順序。我相信，WAKIX 將繼續保持強勁表現，並且我們將憑藉現有令人興奮的管道為未來做好準備。感謝您的提問。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

Thanks. So wanted to ask a high-level question on the orexin. So you have three orexin agonists in mid- to late-stage development, and it's a space that's admittedly getting crowded. So I guess the question is where do you see your orexin-2 receptor agonists fitting in within this emerging armamentarium?

謝謝。所以想問一個關於食慾素的高級問題。因此，有三種食慾素激動劑處於中後期開發階段，而且這個領域無疑正在變得擁擠。所以我想問題是，您認為食慾素-2受體激動劑在這個新興的藥物庫中處於什麼位置？

In sleep/wake, are you looking at the asset in settings beyond sleep/wake as other companies are starting to do? So that's number one.

在睡眠/喚醒模式下，您是否像其他公司一樣開始專注於睡眠/喚醒模式以外的設定中的資產？這是第一點。

And then number 2, can you just talk at a high level about the payer landscape for WAKIX? And what I guess I'm particularly interested in is, as we get more and more generic competition for the oxybates starting next year, how should we think about the payer landscape and the gross to net for WAKIX? Thanks.

然後第二點，您能否概括地談談 WAKIX 的付款人狀況？我想我特別感興趣的是，隨著明年開始我們面臨越來越多的羥基丁酸鹽仿製藥競爭，我們應該如何看待付款人格局和 WAKIX 的毛利與淨利之比？謝謝。

Good morning, David. Thanks for your question. So orexin-2 agonists, obviously a lot of attention, a lot of focus, a lot of interest in the next novel target for narcolepsy, other central disorders of hypersomnolence . The programs are emerging -- still early, still a lot to learn.

早安，大衛。謝謝你的提問。因此，食慾素-2激動劑顯然引起了人們的廣泛關注，人們對於嗜睡症和其他中樞性嗜睡症的下一個新標靶產生了濃厚的興趣。。這些項目才剛出現──還處於早期階段，還有很多東西要學習。

I think I'll turn it over to Kumar in terms of our thoughts on where they could fit in. We still see narcolepsy in terms of the polypharmacy market; chronic neurologic disorder, multiple mechanisms, always can be helpful. Kumar, further thoughts on the other programs and where we fit in.

我想我會將我們對於他們適合做什麼的想法交給庫馬爾。我們仍然從多藥物治療市場的角度看待發作性睡病；慢性神經系統疾病，多種機制，總是有幫助的。庫馬爾，請進一步思考其他項目以及我們適合其中的位置。

Sure. Thank you, Jeff. Hey, good morning, David. Thanks for the question. Look, we see all of these programs as still early, and the data are emerging. We just need to see how the data will pan out from an efficacy and safety perspective and also from a tolerability perspective with the possible exception of Takeda's 861, which is being pursued only in NT1 and is in Phase 3. The other two aspects are in Phase 1b, 2a studies, and we are monitoring these programs very carefully.

當然。謝謝你，傑夫。嘿，早上好，大衛。謝謝你的提問。瞧，我們認為所有這些項目都還處於早期階段，而且數據正在湧現。我們只需要看看數據從功效和安全性角度以及耐受性角度來看會如何發展，但武田的 861 可能是例外，該藥物僅在 NT1 中進行研究，目前處於第 3 階段。另外兩個面向正處於 1b、2a 階段的研究，我們正在非常仔細地監控這些項目。

What we are excited about is really BP1.15205 as [register disclosed] in the past continues to be the highest potent compound compared to any orexin receptor agonists for which the data has been disclosed publicly. And you'll see this high potency translated into robust efficacy in sleepiness in very low doses in the pre-clinical models. And this data will be presented at the upcoming annual sleep meeting in the month of June, and we'll be providing additional color and context around the pre-clinical safety and efficacy.

我們真正感到興奮的是 BP1.15205，因為 [註冊披露] 在過去仍然是與任何已公開披露數據的食慾素受體激動劑相比效力最高的化合物。您將看到，在臨床前模型中，這種高效力在極低劑量下就能轉化為強大的抗嗜睡功效。這些數據將在六月即將召開的年度睡眠會議上公佈，我們將提供更多有關臨床前安全性和有效性的細節和背景資訊。

In terms of your question, David, beyond central disorders of hypersomnolence -- and that is something, we are also carefully monitoring and also doing some of our own experiments as well -- there is a potential that orexin receptor agonist could be helpful in certain other symptom domains, for example, like cognition and potentially mood disorders. These are some of the things that we are working on and also following the field very closely, but it's too early to comment on that.

關於你的問題，大衛，除了嗜睡症的中樞障礙之外——這也是我們正在仔細監測並進行一些我們自己的實驗的情況——食慾素受體激動劑有可能對某些其他症狀領域有幫助，例如認知和潛在的情緒障礙。這些是我們正在研究的一些事情，我們也在密切關注該領域，但現在評論還為時過早。

Thanks, Kumar. In terms of the payer landscape, let me turn it over to Adam. But I think, David, in terms of -- you mentioned the generic oxybates, I think to date, we've not seen any impact with regards to -- on the payer environment for WAKIX with generic oxybates thus far. And also, the ones lately -- in terms of the oxybates vertical, where we that we're pretty well insulated given that it's the first and only non-scheduled product with a differentiated profile, payers not wanting to step WAKIX through an oxybates therapy.

謝謝，庫馬爾。關於付款人情況，讓我把它交給亞當。但是我認為，大衛，就您提到的仿製羥基丁酸鹽而言，我認為到目前為止，我們還沒有看到仿製羥基丁酸鹽對 WAKIX 付款人環境產生任何影響。此外，最近在羥基丁酸鹽垂直領域，我們很好地保護了自己，因為它是第一個也是唯一一個具有差異化特徵的非計劃產品，付款人不想讓 WAKIX 接受羥基丁酸鹽療法。

But further thoughts on payer landscape going forward, Adam?

但是亞當，您對未來付款人的情況還有進一步的想法嗎？

Thank you, Jeff, and thank you, David, for the question. One of the things I've been really impressed with is how the strength and stability of the fundamentals underpinning the business for WAKIX. And I would include payer coverage in that. I think we experienced very broad coverage for WAKIX with over 80% of lives covered, US lives, covered for WAKIX.

謝謝傑夫和大衛提出的問題。令我印象深刻的一件事是 WAKIX 業務基本面的強勁和穩定。我會將付款人保險也納入其中。我認為我們對 WAKIX 的覆蓋範圍非常廣泛，超過 80% 的美國人的生活都得到了 WAKIX 的覆蓋範圍。

And that has really remained consistent, I think, for the past several years despite entries of additional brand and generic oxybates. As Jeff mentioned, plants typically don't step through an oxybate to secure access for WAKIX. And that is, I think, largely because it is a highly differentiated product as the first and only non-scheduled treatment option for these patients.

我認為，儘管有更多品牌和通用的羥基丁酸鹽加入，但過去幾年來確實一直保持一致。正如 Jeff 所提到的，植物通常不會透過氧化物來確保 WAKIX 的通道。我認為這主要是因為它是一種高度差異化的產品，是這些患者的第一個也是唯一的非計劃治療選擇。

And that performance and coverage has really been stable and consistent, I would say for the past several years. We saw no changes -- no significant changes in payer coverage in 1Q. And that is also a reason why I think we remain confident in confirming our full-year guidance for net revenue of between $820 million and $860 million for the year. Thank you.

我想說，過去幾年來，其表現和覆蓋範圍確實一直很穩定且一致。我們沒有看到任何變化——第一季付款人覆蓋範圍沒有重大變化。這也是為什麼我認為我們仍然有信心確認全年淨收入在 8.2 億至 8.6 億美元之間的原因。謝謝。

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Hi, good morning. Thanks for taking my question and, Adam, welcome to the team. And perhaps my first question is just sort of around market dynamics. And how do you see that evolve with the orexins entering the market? I understand that some of the assets are still in Phase 2.

嗨，早安。感謝您回答我的問題，亞當，歡迎加入團隊。也許我的第一個問題只是有關市場動態。隨著食慾素進入市場，您認為這種情況將如何發展？我了解到部分資產仍處於第二階段。

However, in the data that they've generated so far, particularly Takeda as well as Alkermes, seems to indicate that patients can achieve something in -- close to 30 minutes in the MWT. And with that, is there still likely to be polypharmacy in this market? And maybe if you could sort of comment on that and comment on whether you think the dynamics could be different across NT1, NT2 and IH.

然而，從他們迄今為止產生的數據來看，特別是武田和 Alkermes 的數據，似乎表明患者可以在 MWT 中近 30 分鐘內取得一些成果。那麼，這個市場是否還可能存在多種藥物治療呢？也許您可以對此進行評論，並評論您是否認為 NT1、NT2 和 IH 之間的動態會有所不同。

And then just separately regarding EPX-100, what are your thoughts around potentially exploring it in a broader DEE population as opposed to SGS? Thank you.

然後單獨討論 EPX-100，您對在更廣泛的 DEE 人群（而不是 SGS）中探索它有何看法？謝謝。

Good morning, Ami. Thank you for your questions. Yeah, with regards to the orexin-2 agonists and sort of the evolving landscape there, obviously, we are following that closely anticipating what those product profiles may deliver. And as you mentioned, strong efficacy on improving EDS in terms of the data that we've seen, obviously, as we move forward with our next-gen Pitolisant programs and HD looking for kind of greater efficacy going forward in the Pitolisant franchise as well.

早上好，阿米。感謝您的提問。是的，關於食慾素-2激動劑及其不斷發展的前景，顯然，我們正在密切關注並預測這些產品可能帶來的影響。正如您所提到的，從我們所看到的數據來看，它對改善 EDS 具有很強的功效，顯然，隨著我們推進下一代 Pitolisant 計劃，HD 也在尋求 Pitolisant 系列產品未來具有更高的功效。

I think it really comes down to what the overall product profiles will deliver. In efficacy and cataplexy, it's sort of the totality of the evidence, if you will, what the ultimate product profile will look like. And I'll turn it over to Kumar. Any other thoughts with regards to that piece and then on EPX-100?

我認為這實際上取決於整體產品概況將提供什麼。在療效和猝倒方面，這可以說是全部證據，如果你願意的話，最終的產品概況將會是什麼樣子。現在我將把它交給庫馬爾。關於該作品以及 EPX-100 還有其他想法嗎？

Sure, thank you, Jeff. Hey. Good morning, Ami. Thanks for the question. Ami, you did mention about the 30 minutes on MWT; that's true. That's the kind of efficacy that we have seen based on the preliminary data from a couple of products in the [another test], which is good. But still there are many unanswered questions in terms of the response rate, the durability of response, and the overall safety and tolerability profile. And these things need to be figured out.

當然，謝謝你，傑夫。嘿。早上好，阿米。謝謝你的提問。Ami，你確實提到了 MWT 上的 30 分鐘；這是真的。根據 [另一項測試] 中幾種產品的初步數據，我們看到了這種功效，這是很好的。但在反應率、反應持久性以及整體安全性和耐受性方面仍有許多未解答的問題。這些事情都需要弄清楚。

The way we see it is as we progress our orexin receptor agonist, which we believe has the properties to be potentially the best-in-class orexin receptor agonist, as we make progress, we continue to believe that narcolepsy will be a polypharmacy market. Patients with narcolepsy will require more than one medication.

我們認為，隨著我們在食慾素受體激動劑方面的進步，我們相信它具有成為同類最佳食慾素受體激動劑的潛在特性，隨著我們取得進展，我們繼續相信發作性睡病將成為一個多藥物治療市場。患有嗜睡症的患者需要多種藥物。

As you know, it's not just excessive daytime sleepiness. They also have disrupted nighttime sleepiness. They have cataplexy. They have hypnagogic hallucinations, fatigue, and a host of other symptoms. That's exactly one of the reasons why we are targeting our Pitolisant HD formulation towards fatigue, which is a symptom that is experienced by about 60% to 70% of patients with narcolepsy for which there are no approved treatments and [histonotic] mechanism of action specifically is suited to treat fatigue symptoms, and we demonstrated that in our DM1 study.

如你所知，這不僅僅是白天過度嗜睡的問題。它們也會擾亂夜間的睡眠。他們得了猝倒症。他們出現入睡前幻覺、疲勞以及許多其他症狀。這正是我們將 Pitolisant HD 配方瞄準疲勞的原因之一，大約 60% 至 70% 的嗜睡症患者都會出現疲勞症狀，目前尚無批准的治療方法，而 [histonotic] 作用機制特別適合治療疲勞症狀，我們在 DM1 研究中證明了這一點。

So that's where we are with orexin receptor agonist and how we are thinking about the landscape.

這就是我們對食慾素受體激動劑的現狀以及我們對前景的看法。

To your question about EPX-100, yes, definitely the option of going -- or pursuing a broader DEE indication is available. Right now, we are focused on our two Phase 3 studies, ARGUS study in Dravet syndrome and LIGHTHOUSE study in Lennox-Gastaut syndrome.

對於您關於 EPX-100 的問題，是的，絕對可以選擇——或者追求更廣泛的 DEE 指示。目前，我們專注於兩項 3 期研究，即 Dravet 症候群的 ARGUS 研究和 Lennox-Gastaut 症候群的 LIGHTHOUSE 研究。

Both of these studies are up and running, actively recruiting patients, and we are evaluating potentially adding other DEE indication. But we just need to look at the benefit-risk balance by making some of these studies more heterogeneous by adding other patients. So that's an option that is definitely available and we are evaluating.

這兩項研究均已啟動並正在積極招募患者，我們正在評估可能添加其他 DEE 適應症。但我們只需要透過增加其他患者使這些研究變得更加異質化，從而觀察收益風險平衡。所以這是一個絕對可行的選擇，我們正在評估。

Patrick Trucchio, HC Wainwright.

派崔克·特魯基奧、HC·溫賴特。

Thanks. Good morning. Just a couple of questions from me. The first is I'm wondering if you can discuss the drivers of your revenue guidance and specifically what we should be looking for to suggest the year's revenue should trend to the higher end of the range rather than the lower end.

謝謝。早安.我只想問幾個問題。首先，我想知道您是否可以討論一下您的收入預期的驅動因素，特別是我們應該尋找什麼來表明今年的收入應該趨向於範圍的高端而不是低端。

And then secondly, I'm wondering if you can preview any of the design elements from the upcoming Phase 3 trials for Pitolisant HD in narcolepsy and IH, including whether fatigue and sleep inertia endpoints may be formally powered in the HD trial for differentiated labeling.

其次，我想知道您是否可以預覽即將進行的 Pitolisant HD 治療嗜睡症和 IH 的 3 期試驗中的任何設計元素，包括疲勞和睡眠慣性終點是否可以在 HD 試驗中正式獲得差異化標記的支持。

Good morning, Patrick. Thanks for your questions. So, Adam, in terms of drivers of the business and Sandip, if you want to comment as well.

早上好，派崔克。感謝您的提問。所以，亞當，就業務驅動力和桑迪普而言，如果你也想發表評論的話。

Sure, I can jump in. Thank you, Jeff, and thank you for the question. The primary driver of growth for the remainder of the year is going to be continued sequential additions of patients on therapy. And this is something we've seen historically very consistently.

當然，我可以加入。謝謝傑夫，謝謝你提出這個問題。今年剩餘時間增長的主要動力將是接受治療的患者數量的持續增加。我們從歷史上就常看到這樣的情況。

Again, back to the fundamentals of the business here, a very strong and stable, continued progression of average patients on therapy. This quarter in Q1, we achieved 7,200 patients on WAKIX. We exited the quarter actually at 7,300. So we continue to see that strong momentum moving into the rest of the year. And we would expect to see that growth and performance continue.

再次回到這裡的業務基本面，即接受治療的普通患者人數非常強勁、穩定且持續成長。本季度第一季度，我們在 WAKIX 上接待了 7,200 名患者。本季結束時我們的股價實際上為 7,300。因此，我們將繼續看到這種強勁勢頭延續到今年剩餘時間。我們期望看到這種成長和表現持續下去。

As we think about that patient growth, we typically have been discussing, how do you grow the top-line referrals, how do you make sure that we're converting patients to ensure that referrals are actually dispensed, and what is the adherence and compliance with that therapy over time? I think in each of those buckets, you see very strong stable fundamentals, and we would continue expect that the remainder of this year.

當我們考慮患者的成長時，我們通常會討論，如何增加頂線轉診，如何確保我們正在轉化患者以確保轉診確實得到執行，以及隨著時間的推移，對該療法的依從性和依從性如何？我認為，在每個領域中，你都會看到非常強勁、穩定的基本面，我們預計今年剩餘時間裡基本面將繼續保持穩定。

And I would just ask Patrick, I think it speaks to the underlying opportunity in the narcolepsy market. So again, large market -- 80,000 diagnosed patients, year six in the market continued to grow, continued sort of momentum, and then the differentiated product profile.

我只想問帕特里克，我認為這說明了嗜睡症市場的潛在機會。所以，再說一次，這是一個巨大的市場——80,000 名確診患者，第六年市場繼續成長，繼續保持成長勢頭，然後是差異化的產品配置。

Again, we tapped into the 9,000 HCPs, prescribing, 5,000 of whom are not -- don't participate in an oxybate REM, continue to penetrate across that segment. About 50% or so penetrated as well as the depth of the 4,000 HCPs with the larger clinics more patients.

再次，我們利用了 9,000 名開立處方的 HCP，其中 5,000 名不參與 - 不參與羥基丁酸鹽 REM，繼續滲透到該領域。大約有 50% 左右的滲透率以及 4,000 名 HCP 的深度，診所越大，患者就越多。

So it is the rhythm of the business, if you will, as we said now going into year six in the market. Large market opportunities, differentiated profile, strong underlying business fundamentals that are consistent, and we're confident. We are confident in WAKIX being on its way to a $1 billion-plus opportunity in narcolepsy alone.

所以，如果你願意的話，這就是業務的節奏，正如我們所說的，現在市場已經進入第六年。龐大的市場機會、差異化的產品組合、強勁的持續業務基礎，讓我們充滿信心。我們相信，WAKIX 僅在嗜睡症治療領域就有望獲得 10 億美元以上的價值。

Thank you, Jeff. Hey. Good morning, Patrick. Thank you for your questions on Pitolisant HD Phase 3 programs. We have already disclosed the study designed for idiopathic hypersomnia, which is aligned with the regulatory agency. It's going to be a double-blind, randomized, placebo-controlled parallel study.

謝謝你，傑夫。嘿。早上好，派崔克。感謝您對 Pitolisant HD 第三階段計劃提出的問題。我們已經公開了針對特發性嗜睡症設計的研究，該研究與監管機構保持一致。這將是一項雙盲、隨機、安慰劑對照的平行研究。

Phase 3 narcolepsy study, we haven't disclosed the design yet. And we will provide that information as we get ready to initiate the study.

第三階段嗜睡症研究，我們尚未揭露設計。當我們準備開始研究時，我們將提供這些資訊。

And your other question was around fatigue. We have done some leading-edge work in fatigue already. We have been working on this for more than two years now. We completed a qualitative research study to look at the instruments, to measure specifically fatigue, specifically in patients with narcolepsy. And we are about to complete a really large longitudinal study looking at the prevalence and impact and the stability of symptoms of fatigue in patients with narcolepsy. The goal is certainly to get fatigue as an indication in narcolepsy sooner or later, and we will be providing more information on that as we get closer to initiating the narcolepsy study. Thank you.

您的另一個問題是關於疲勞的。我們在疲勞方面已經做了一些前沿工作。我們為此已經努力了兩年多了。我們完成了一項定性研究，對用於測量疲勞程度（特別是嗜睡症患者的疲勞程度）的工具進行了研究。我們即將完成一項大型縱向研究，觀察嗜睡症患者疲勞症狀的盛行率、影響和穩定性。我們的目標肯定是遲早將疲勞作為嗜睡症的一個指徵，隨著嗜睡症研究的啟動，我們將提供更多相關資訊。謝謝。

David Hoang, Deutsche Bank.

德意志銀行的 David Hoang。

Hi. Thanks so much for taking my questions. Adam, welcome to the team. I want to ask a little bit about ZYN002 in Fragile X. If you do get positive data in hand, how quickly do you think you could file the NDA for that molecule? And can you just give us a sense of what commercialization of 002 in the Fragile X market might look like, how do you think about the value proposition of this product? And are there other analogs in rare neurological diseases that we could look at?

你好。非常感謝您回答我的問題。亞當，歡迎加入團隊。我想問一下 Fragile X 中的 ZYN002 的問題。如果您確實獲得了積極的數據，您認為您多快可以為該分子提交 NDA？您能否向我們簡單介紹一下 002 在脆性 X 市場的商業化情況，您如何看待該產品的價值主張？我們是否可以研究其他罕見神經系統疾病的類似物？

Yeah. Good morning, David. Thanks for your question. Really excited about the ZYN 002 Fragile X opportunity. Kumar, you want to talk about the development part, and then we can talk about market opportunity.

是的。早安，大衛。謝謝你的提問。對於 ZYN 002 Fragile X 的機會感到非常興奮。庫馬爾，你想談談發展部分，然後我們可以談談市場機會。

Sure. Thank you, Jeff. Hey, good morning, David. Yeah. Fragile X syndrome, look, very excited for the top-line data. As we disclosed this morning, we completed recruitment and closed for new screenings. We are on track for top-line data in 3Q of this year.

當然。謝謝你，傑夫。嘿，早上好，大衛。是的。脆性 X 綜合徵，看起來，對頂線數據感到非常興奮。正如我們今天早上所披露的那樣，我們已經完成了招募並結束了新的篩選。我們預計將取得今年第三季的營收數據。

And if the results are positive, we have the ability, the opportunity to bring the very first approved treatment to patients with Fragile X syndrome. Once we get the top-line data, David, the goal is to file NDA as soon as possible. And given the unmet need, significant unmet need in this patient population, I think it's reasonable to expect a priority review in an indication like this.

如果結果是正面的，我們就有能力、有機會為脆性 X 症候群患者帶來首個核准的治療方法。大衛，一旦我們獲得頂線數據，目標就是盡快提交保密協議。考慮到該患者群體中未滿足的需求，重大未滿足的需求，我認為對這樣的適應症進行優先審查是合理的。

So there will be an expedited timelines to submission of NDA. And I'm sure the FDA will also show the urgency to quickly review the data package and give the decision on PDUFA.

因此，提交保密協議 (NDA) 的時間將會加快。我相信 FDA 也會表現出緊迫感，迅速審查資料包並就 PDUFA 做出決定。

And, of course, the other thing is in the background we are working expeditiously on 22q. We have aligned with the regulatory agencies on the primary endpoint and the Phase 3 study. As we speak, we are getting ready to initiate Phase 3 study in 22q as well, another rare indication. Approximately 80,000 patients each in the US and Europe.

當然，另一件事是我們正在幕後迅速開展 22q 工作。我們已與監管機構就主要終點和第 3 階段研究達成協議。正如我們所說，我們正準備啟動 22q 的第三階段研究，這是另一個罕見的跡象。美國和歐洲各有大約 80,000 名患者。

And as we mentioned in the past, we have global rights for ZYN002 and not -- to go back on Fragile X syndrome, one thing is the study design meets the requirements of not just the FDA but also EMA for an indication for Fragile X syndrome.

正如我們過去提到的，我們擁有 ZYN002 的全球權利，而不是——回到脆性 X 綜合徵，一件事是研究設計不僅滿足 FDA 的要求，也滿足 EMA 對脆性 X 綜合徵適應症的要求。

Do, David, suffice it to say with positive data, we will move swiftly in terms of preparing an NDA and submitting that. In terms of the market opportunity and go-to market, so about 80,000 patients living with Fragile X as well as 22q in the US and similar in the EU as well with global rights. We see this -- I think about 60,000 by claims data -- so significant opportunity for a rare disease.

大衛，只要有積極的數據，我們就會迅速準備保密協議並提交。就市場機會和進入市場而言，美國約有 80,000 名患有脆性 X 綜合徵和 22q 綜合徵的患者，歐盟也有類似情況，並且擁有全球權利。我們看到了這一點——我認為索賠數據大約有 60,000 個——對於治療罕見疾病來說這是一個重大機會。

We see this as a sort of centers of excellence model, if you will, with regards to neurobehavioral syndromes and those types of disorders. We have a lot of institutional knowledge in the space that came over from our acquisition of Zynerba, you know it well. And then our sort of world-class patient advocacy team is fully engaged with the Fragile X patient community, listening to them, kind of understanding the unmet needs.

如果你願意的話，我們可以將其視為一種針對神經行為症候群和那些類型的疾病的卓越中心模型。我們透過收購 Zynerba 在該領域積累了大量的機構知識，這一點您非常了解。然後，我們世界一流的患者權益倡導團隊將充分參與脆性 X 綜合徵患者社區，傾聽他們的意見，了解未滿足的需求。

You'll hear more from Adam going forward in terms of you know launch preparation as we plan for success with high conviction in the top-line data.

您將從亞當那裡聽到更多關於發布準備的信息，因為我們對頂線數據充滿信心，計劃取得成功。

Ash Verma, UBS.

瑞銀的 Ash Verma。

Thanks for taking the question. Congrats on the quarter. So, maybe just on Fragile X, I wanted to understand, there is this competitor, Shionogi, that has a program, they told me last, which is reading out in the second quarter. And they've shown prior Phase 2 data with cognitive assessment.

感謝您回答這個問題。恭喜本季取得佳績。因此，也許只是關於 Fragile X，我想了解一下，有一個競爭對手 Shionogi，他們上次告訴我，他們有一個計劃，將在第二季度公佈。他們也展示了認知評估的第二階段前期數據。

What are your thoughts on PDE4D [anesthetic] inhibitor approach? And I saw like their endpoint is different versus what you're studying. Just wanted to make sure that these are both FDA approved or not.

您對 PDE4D [麻醉劑] 抑制劑方法有何看法？我發現他們的終點與你所研究的有所不同。只是想確保這些是否都經過 FDA 批准。

And then secondly, on WAKIX, so wanted to understand like these new patients that you're getting in, can you provide us a split of how much of that is coming from [alpha-beta] experienced versus naive patients.

其次，關於 WAKIX，我想了解一下您接收的這些新患者，您能否為我們提供一個比例，看看其中有多少來自 [alpha-beta] 有經驗的患者，有多少來自初次接受治療的患者。

Thanks. Okay. Good morning, Ash. Thanks for your question. In terms of the Shionogi program, just very briefly, obviously following that closely. Very different program, as you mentioned, the primary outcome around cognition and cognitive function only in male patients.

謝謝。好的。早安，阿什。謝謝你的提問。就 Shionogi 計劃而言，只是非常簡短，顯然緊隨其後。正如您所提到的，這是一個非常不同的項目，其主要結果僅圍繞男性患者的認知和認知功能。

So if Kumar, you want to comment further, but our program is very different -- as well as the importance of any new treatments for patient populations with unmet medical needs.

因此，如果庫馬爾 (Kumar) 想要進一步評論，但我們的計劃非常不同——以及任何新療法對於未滿足醫療需求的患者群體的重要性。

No. I think you covered everything. Yes, Ash, it does apply zatolmilast PDE4D inhibitor, specifically looking at symptoms of cognition in male patients only, who have a relatively higher level of baseline cognitive function. Whereas in RECONNECT, we're looking at neurobehavioral symptoms which are extremely prevalent, in fact, prevalent in every patient with Fragile X syndrome and also the most bothersome symptoms when it comes to patients and their caregivers.

不。我認為你已經涵蓋了所有內容。是的，Ash，它確實應用了 zatolmilast PDE4D 抑制劑，具體來說，它只關注男性患者的認知症狀，這些患者的基線認知功能水平相對較高。而在 RECONNECT 計畫中，我們關注的是極為普遍的神經行為症狀，事實上，這些症狀在每位脆性 X 症候群患者中都很普遍，而且對於患者及其照護者來說，這些症狀也是最令人困擾的。

Thanks, Kumar. Adam, you want to take it?

謝謝，庫馬爾。亞當，你想拿走它嗎？

Sure. Thank you, Jeff. Thanks for the question. Yeah, so I guess in terms of sourcing of patients, I think Jeff mentioned before, the polypharmacy nature of the therapeutic approach here. So the reality is the majority of patients that we're seeing referred for WAKIX have been on one or multiple other therapies prior to that referral. That's common. And that's going to be true for any product for sleep/wake.

當然。謝謝你，傑夫。謝謝你的提問。是的，所以我想就患者來源而言，我認為傑夫之前提到過，這裡的治療方法具有多重用藥性質。因此，實際情況是，我們看到的大多數接受 WAKIX 治療的患者在轉診之前已經接受過一種或多種其他療法。這很常見。對於任何睡眠/喚醒產品都是如此。

And then even when patients are on WAKIX therapy, we continue to see that polypharmacy approach. And so the majority of patients on the WAKIX therapy are also on one or additional other therapeutic options. And certainly, oxybates being a prominent option that HCPs have access to, that's going to be a proportional portion of those patients that would also have concomitant oxybate use.

即使患者正在接受 WAKIX 治療，我們仍然會看到多種藥物治療的方法。因此，大多數接受 WAKIX 治療的患者也會選擇一種或多種其他治療方案。當然，由於羥基丁酸鹽是醫療保健人員可以使用的主要選擇，因此相當一部分患者也會同時使用羥基丁酸鹽。

Yeah. And I think the experience with concomitant use, about 10% to 15% of patients on WAKIX also on an oxybate, it's been fairly consistent since launch.

是的。我認為，自推出以來，同時使用 WAKIX 的患者中約有 10% 至 15% 也使用羥基丁酸鹽，這一經驗一直相當一致。

Jason Gerberry, Bank of America.

美國銀行的 Jason Gerberry。

Hey, guys. Thanks for taking my questions. Just on the orexin data at SLEEP, I'm wondering if you can preview a little bit like what we'll get -- I think when I looked at some of the other players who were in the clinic when they were evaluating their drugs pre-clinically, looking at the DTA mouse models -- and what endpoints will you give -- and when I look at like Centessa's versus Takeda's data, some of the endpoint measures are a little bit different, making comparisons a little bit difficult. But will you give latency to sleep or latency to cataplexy so we can benchmark and get a sense that the potency selectivity argument is starting to translate on the efficacy side?

嘿，大家好。感謝您回答我的問題。僅就 SLEEP 的食慾素數據而言，我想知道您是否可以預覽一下我們將獲得的內容 - 我想當我查看一些其他參與者在臨床前評估他們的藥物時，查看 DTA 小鼠模型 - 以及您將給出哪些終點 - 當我查看 Centessa 與 Takeda 的數據時，一些終點測量有點不同，這使得比較有點困難。但是，您是否會給出睡眠潛伏期或猝倒潛伏期，以便我們可以進行基準測試並了解效力選擇性論點是否開始在功效方面得到轉化？

And then just asking the polypharmacy question a little bit differently, what proportion of payers are amenable to two proprietary brand medicines in the narcolepsy setting? Just trying to get a sense because as new proprietary -- presumably expensive medicines come on board, just wondering how payers will be amenable to covering multiple brands. Thanks.

然後，稍微換一種方式問一下多重用藥問題，在發作性睡病治療中，有多少比例的付款人願意接受兩種專利品牌藥物？只是想了解一下，因為隨著新的專利藥物（大概是昂貴的藥物）的出現，只是想知道付款人將如何接受覆蓋多個品牌。謝謝。

Good morning, Jason. Thanks for the question. Kumar, on upcoming data at SLEEP?

早上好，傑森。謝謝你的提問。庫馬爾，關於 SLEEP 即將發布的數據？

Sure. Hey, good morning, Jason. Thanks for the question. Yes, we will be presenting a comprehensive pre-clinical safety and efficacy data at the upcoming meeting in June in Seattle. And as I mentioned earlier during the call, I mean, you'll see high potency translated into robust efficacy in sleepiness at very low doses in the pre-clinical animal models.

當然。嘿，早上好，傑森。謝謝你的提問。是的，我們將在 6 月於西雅圖舉行的會議上展示全面的臨床前安全性和有效性數據。正如我之前在電話中提到的那樣，您將看到在臨床前動物模型中，高效力轉化為極低劑量下對嗜睡的強大功效。

In terms of specifically the model and the parameters that we will be discussing, you can expect to see the standard parameters like sleep latency, wakefulness time. In a mice model that is considered as standard for preclinical studies, you're right, Jason, sometimes it's hard to compare the data in pre-clinical models because of the use of different animal models, different experimental conditions, different points in time, but we will be showing data that will show that the efficacy is consistent with the very high potency that we have been talking about and also the pre-clinical safety data in GLP studies that will look very good.

就我們將要討論的具體模型和參數而言，您可以看到睡眠潛伏期、覺醒時間等標準參數。在被視為臨床前研究標準的小鼠模型中，您說得對，傑森，有時很難比較臨床前模型中的數據，因為使用了不同的動物模型、不同的實驗條件、不同的時間點，但我們將顯示數據，表明功效與我們一直在談論的非常高的效力一致，而且 GLP 研究中看起來非常好的臨床前安全性數據。

Yeah, wait for the SLEEP meeting.

是的，等待睡眠會議。

And Jason, I think your next question was about concomitant use of WAKIX and oxybates in the payer landscape. And I think that the experience has been, and we've said this before, given all the plans and each plan with not a lot of patients in the plans that it's almost more in terms of administratively with regards to managing both of those therapies. So there's not been any pushback, I think, with regards to it's not a big part of their budgets.

傑森，我想你的下一個問題是關於付款人環境中 WAKIX 和氧化物類藥物的同時使用。而且我認為，經驗是這樣的，我們之前也說過，考慮到所有的計劃，而且每個計劃中都沒有很多患者，因此在管理這兩種療法方面，幾乎更多的是在行政方面。所以我認為，由於這佔其預算的比例不大，所以沒有遇到任何阻力。

So patients on both WAKIX and a branded oxybate has not been a challenge in the market for us because each of the plans don't have a lot of patients given that it's a rare disease.

因此，同時使用 WAKIX 和品牌羥基丁酸鹽的患者對我們來說並不是一個市場挑戰，因為考慮到這是一種罕見疾病，每種計劃都沒有很多患者。

Charles Duncan, Cantor Fitzgerald.

查爾斯鄧肯、康托菲茨傑拉德。

Hi, morning, and team. Congrats on a nice quarter. Thanks for taking our question. I had a commercial question and then a pipeline question. May also have a strategy question at the end.

大家好，早安，各位團隊。恭喜本季取得良好業績。感謝您回答我們的問題。我有一個商業問題，然後是一個管道問題。最後可能還會有策略問題。

But with regard to the commercial question, I guess Adam mentioned exiting the quarter with about 7,300 patients on. I guess I'm wondering five weeks into the quarter, how do you feel about the trends for WAKIX now?

但關於商業問題，我想亞當提到本季結束時大約有 7,300 名患者。我想知道本季已經過去五週了，您對 WAKIX 的趨勢有何看法？

And would the guidance depend more on, call it, external initiative or external factors such as demand or more on internal efforts such as tweaks to the marketing program that you plan for -- that you're contemplating for WAKIX?

該指導是否會更多地取決於所謂的外部主動性或外部因素（例如需求），還是更多地取決於內部努力（例如對您為 WAKIX 計劃的營銷計劃的調整）？

Thanks for the question. So what I can speak to is really the strong continued performance in Q1. And in Q1, we typically do see the traditional seasonality. We've seen that every year for the five years now moving on to six years since launch. And that has to do with the traditional payer resets that happen at the beginning of the year. So as patients move coverage, they have to reestablish prior authorizations and steps, and that takes a little bit of time.

謝謝你的提問。因此我可以說的是第一季的持續強勁表現。在第一季度，我們通常會看到傳統的季節性。我們每年都看到這種情況，從推出到現在已經過了五年，六年了。這與年初發生的傳統付款人重置有關。因此，當患者轉移保險時，他們必須重新建立先前的授權和步驟，這需要一點時間。

So that does have an impact on Q1 patient numbers, but that's something that's seen actually not just for WAKIX; it's seen across sleep/wake. It's also seen actually across the industry.

所以這確實會對第一季的患者數量產生影響，但實際上這不僅出現在 WAKIX 中；它還出現在睡眠/清醒階段。事實上，整個產業也都存在這種情況。

So that's the typical seasonality that we would expect to see, and we weathered that successfully this quarter. As I mentioned, the momentum continues very strong as we're exiting the quarter, and we continue to have confidence for that full-year revenue guidance between $820 million and $860 million for the full year.

這是我們預計會看到的典型季節性，本季我們成功度過了這段時期。正如我所提到的，我們在本季結束時勢頭依然強勁，我們仍然對全年營收預期在 8.2 億美元至 8.6 億美元之間充滿信心。

That sounds like it's demand-driven, correct?

這聽起來像是需求驅動的，對嗎？

So, yeah. So certainly, the growth is, as Jeff said before, it's going to be primarily driven by demand as a result of the highly differentiated profile of WAKIX. But I will mention as well one of the things I've been really impressed with is the commercial model that has been put in place to support patients, to support HCPs, as well as caregivers. I think it's a key driver of performance.

是的。因此，正如 Jeff 之前所說，成長肯定主要由需求驅動，因為 WAKIX 具有高度差異化的形象。但我還要提到，令我印象深刻的一件事是已經建立的商業模式，用於支持患者、支持 HCP 以及護理人員。我認為這是績效的關鍵驅動因素。

It's not just the model itself, but also how it's used with all referrals going into a single central hub, very tight distribution through three specialty pharmacies, and a broad set of data that we're able to capture on patients individually and longitudinally that allows us to deploy intelligent investment decisions, resource planning, and make real-time decisions as we're seeing that data updated on a daily basis. So I think that's also an element.

這不僅僅是模型本身，還包括如何使用它，所有轉診都進入一個中央樞紐，透過三個專業藥房進行非常緊密的分發，以及我們能夠單獨和縱向捕獲患者的大量數據，這使我們能夠部署智能投資決策、資源規劃，並在我們看到數據每天更新時做出實時決策。所以我認為這也是一個因素。

Okay. That's helpful. Sounds like no major changes in terms of the sales strategy.

好的。這很有幫助。聽起來銷售策略方面沒有重大變化。

No major changes. I think it's really what I said before. You're right. Underlying demand remains strong. Market opportunity remains large, strong underlying fundamentals. And I think no major changes to the strategy.

沒有重大變化。我想這確實是我之前說的。你說得對。潛在需求依然強勁。市場機會依然巨大，基本面強勁。我認為戰略不會發生重大變化。

We will see opportunities obviously, as the brand matures, to make tweaks along the way. I think Adam is bringing fresh perspective and thinking with regards to that. And we see continued opportunity ahead in our core franchise for the $1 billion-plus in narcolepsy as we prepare to initiate the Phase 3 trials for Pitolisant HD in both narcolepsy and IH in the fourth quarter.

隨著品牌的成熟，我們顯然會看到機會並做出調整。我認為亞當對此帶來了新的視角和思維。在我們準備於第四季度啟動 Pitolisant HD 在治療嗜睡症和間歇性嗜睡症的 3 期臨床試驗之際，我們看到，我們的核心特許經營權在治療嗜睡症方面仍擁有超過 10 億美元的市場機會。

So we are poised with a target PDUFA in 2028 to transition the Pitolisant franchise with utility patents to 2044 well into the future to extend that franchise and generate significant value.

因此，我們準備在 2028 年制定 PDUFA 目標，將 Pitolisant 特許經營權及其實用專利過渡到 2044 年，以延長該特許經營權並創造巨大價值。

That's a great segue, Jeff, to my last question, which is Pitolisant HD. In terms of the timing of that Phase 3 start, I'm kind of wondering what the rate limiting step is. I know that you run a lean and mean operation. So lots going on in the pipeline generally, but are there any experimental results you're waiting for to be able to operationalize that Phase 3 with Pitolisant HD in narcolepsy as well as perhaps IH by the end of the year?

傑夫，這很好地引出了我的最後一個問題，即 Pitolisant HD。就第三階段開始的時間而言，我有點想知道限速步驟是什麼。我知道你們經營的是精簡型企業。總體來說，有很多事情正在進行中，但是您是否正在等待任何實驗結果，以便能夠在年底前將 Pitolisant HD 用於治療發作性睡病以及 IH 的第三階段臨床研究？

Yeah, Charles. I think it's mainly just finalizing the formulation work. I'll turn it over to Kumar, but all of the preparation is in motion for those. And Kumar, do you want to provide more color?

是的，查爾斯。我認為主要只是完成製定工作。我會把它交給庫馬爾，但所有的準備工作都在進行中。庫馬爾，你想提供更多顏色嗎？

Yeah, sure. Thanks, Jeff. Hey. Good morning, Charles. We always said we will initiate the Phase 3 studies both in narcolepsy and in IH in the fourth quarter of this year. And we are on track to initiate both the studies in narcolepsy and in IH -- large global Phase 3 studies.

是的，當然。謝謝，傑夫。嘿。早上好，查爾斯。我們一直說我們將在今年第四季啟動針對嗜睡症和IH的第三階段研究。我們正按計畫啟動針對嗜睡症和IH的研究—大型全球3期研究。

In terms of what happens, Charles, these are large studies, registrational studies. So a lot of work that needs to happen in terms of the protocol finalization, the regulatory alignment, IND submission, and the formulation development. These are Phase 3 studies, so we need commercial-ready formulation work that needs to be completed before you start Phase 3 study.

就發生的事情而言，查爾斯，這些都是大型研究、註冊研究。因此，在協議最終確定、監管協調、 IND 提交和配方開發方面還有很多工作要做。這些是第 3 階段研究，因此我們需要在開始第 3 階段研究之前完成商業化的配方工作。

So we are just checking all the boxes and making steady progress to initiate both the studies in fourth quarter of this year. And we are committed to the potential target PDUFA date in 2028, as Jeff mentioned well before, the loss of patent on WAKIX, which is Q1 2030.

因此，我們正在檢查所有事項並穩步推進，以便在今年第四季度啟動這兩項研究。我們致力於在 2028 年實現 PDUFA 的潛在目標日期，正如 Jeff 之前提到的那樣，WAKIX 的專利失效日期是 2030 年第一季。

Thank you. I'm showing no further questions. I would now like to turn the call back over for any closing remarks.

謝謝。我沒有其他問題。現在我想將電話轉回以便發表結束語。

Thanks, Angela. I want to thank everyone for joining our call today. Harmony is well positioned to continue to grow our enterprise and generate durable value going forward. Thank you for your interest in Harmony and have a great day.

謝謝，安吉拉。我要感謝大家今天參加我們的電話會議。Harmony 已做好準備，繼續發展我們的企業並在未來創造持久的價值。感謝您對 Harmony 的關注並祝您度過愉快的一天。

This does conclude today's Harmony Biosciences first-quarter 2025 financial results conference call. You may now disconnect your line and have a wonderful day.

今天的 Harmony Biosciences 2025 年第一季財務業績電話會議就此結束。現在您可以斷開線路並享受美好的一天。