Harmony Biosciences Holdings Inc (HRMY) 2023 Q4 法說會逐字稿

Good morning. My name is Brittany and I will be your conference operator today. At this time, I would like to welcome everyone to the Harmony Biosciences' fourth quarter and full year 2023 financial results conference call. (Operator Instructions) Please be advised that today's conference may be recorded. I would now like to turn the call over to Luis Sanay, Head of Investor Relations. Please go ahead.

早安.我叫布列塔尼，今天我將擔任你們的會議操作員。此刻，我歡迎大家參加和諧生物科學公司第四季和2023年全年財務業績電話會議。（操作員指示）請注意，今天的會議可能會被錄音。我現在想將電話轉交給投資人關係主管 Luis Sanay。請繼續。

Thank you, operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences' fourth quarter and full year 2023 financial results and provide a business update.

謝謝你，接線生。大家早安，感謝您今天加入我們，我們將回顧 Harmony Biosciences 第四季和 2023 年全年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 a reconciliation of our GAAP, the non-GAAP financial measures. At this stage of our life cycle, we believe non-GAAP financial results better represent the underlying business performance. Our speakers on today's call are Dr. Jeffrey Dayno, President and CEO, Jeffrey Dierks, Chief Commercial Officer, Dr. Kumar Budur, Chief Medical Officer, and Sandip Kapadia, Chief Financial Officer and Chief Administrative Officer.

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（非 GAAP 財務指標）的調整表。在我們生命週期的這個階段，我們相信非公認會計原則財務表現更好地代表了基本的業務績效。今天電話會議的發言人包括總裁兼首席執行官 Jeffrey Dayno 博士、首席商務官 Jeffrey Dierks、首席醫療官 Kumar Budur 博士以及首席財務官兼首席行政官 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. I would now like to turn the call over to Dr. Jeffrey Dayno. Jeff?

提醒一下，我們今天將根據我們當前的期望和信念發表前瞻性聲明。這些陳述存在一定的風險和不確定性。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向 SEC 提交的文件中提到的風險因素，以了解更多詳細資訊。我現在想把電話轉給傑弗瑞·戴諾醫生。傑夫？

Thank you, Luis, and thanks, everyone, for joining our conference call today. Harmony continues to be a growth story, as demonstrated by our team's accomplishments throughout 2023. We delivered another strong year of performance across the organization, growing revenue and average number of patients on WAKIX. We advanced all our clinical development programs for pitolisant, move to the next generation or next gen formulations of pitolisant into the clinic and expanded our pipeline and diversified our portfolio with the acquisition of Zynerba and the ongoing Phase 3 clinical trial in patients with Fragile X syndrome.

謝謝路易斯，也謝謝大家今天參加我們的電話會議。正如我們團隊在 2023 年所取得的成就所證明的那樣，Harmony 仍然是一個成長的故事。我們整個組織又取得了強勁的業績，WAKIX 的收入和平均患者數量不斷增長。我們推進了所有的pitolisant臨床開發計劃，將pitolisant的下一代或下一代製劑轉移到臨床，並通過收購Zynerba和正在進行的針對脆性X綜合徵患者的3期臨床試驗擴大了我們的產品線並使我們的產品組合多樣化。

Yesterday, we announced that FDA granted priority review for our supplemental NDA or sNDA for WAKIX in pediatric narcolepsy with a PDUFA date of June 21. Earlier this week, we also shared that FDA granted orphan drug designation for pitolisant for the treatment of Prader-Willi syndrome or PWS as we are preparing to initiate our pivotal Phase 3 TEMPO study in patients with PWS down to age six. All of this reflects momentum across our organization from our commercial business with WAKIX in narcolepsy to our clinical development programs as well as positive interactions with FDA related to these programs.

昨天，我們宣布 FDA 授予我們 WAKIX 治療小兒發作性睡病的補充 NDA 或 sNDA 優先審查， PDUFA 日期為 6 月 21 日。本週早些時候，我們還分享了 FDA 授予了用於治療 Prader-Willi 症候群或 PWS 的 pitolisant 孤兒藥資格，因為我們正準備在 6 歲以下 PWS 患者中啟動關鍵的 3 期 TEMPO 研究。所有這些都反映了我們整個組織的勢頭，從我們與 WAKIX 的嗜睡症商業業務到我們的臨床開發項目，以及與 FDA 就這些項目進行的積極互動。

These outcomes also reflect excellence in execution and the dedication of our team to deliver on the strategy we have laid out and are executing on. In addition, we returned capital to shareholders via our share repurchase program, and we'll continue to take an opportunistic approach to this program throughout this year. I am very excited for the year ahead and believe that Harmony is poised to accelerate our growth in 2024.

這些成果也反映了我們團隊的卓越執行力和奉獻精神，以實現我們已經制定和正在執行的策略。此外，我們也透過股票回購計畫向股東返還資本，今年我們將繼續對此計畫採取機會主義態度。我對未來的一年感到非常興奮，並相信 Harmony 將在 2024 年加速我們的成長。

For the fourth quarter, we reported WAKIX's net revenue of $168.4 million and full year net revenue was $582 million, representing growth of 31% and 33% respectively. This result demonstrates the significant underlying demand for WAKIX and the durability of the brand going into year five in the market.

我們報告第四季度 WAKIX 淨收入為 1.684 億美元，全年淨收入為 5.82 億美元，分別成長 31% 和 33%。這一結果表明了 WAKIX 的巨大潛在需求以及該品牌進入市場第五年的持久性。

Other factors that drive our confidence in our ability to grow WAKIX include it's meaningfully differentiated product profile, which results in its broad clinical utility, coupled that with our ability to reach the broad prescriber universe of approximately 9,000 HCPs who see and treat almost 100% of the diagnosed narcolepsy patient opportunity. We have seen growth in patients on WAKIX and prescribers every quarter since launch, even with the entrance of new branded and generic oxybate treatment options coming into the market over the past few years.

其他促使我們對發展WAKIX 的能力充滿信心的因素包括它具有有意義的差異化產品概況，這導致了其廣泛的臨床實用性，再加上我們有能力接觸到約9,000 名HCP 的廣泛處方者群體，他們幾乎100% 地治療和治療了所有患者。診斷發作性睡病患者的機會。自推出以來，我們看到 WAKIX 的患者和處方者每季都在成長，即使過去幾年新品牌和仿製藥羥丁治療方案進入市場也是如此。

Finally, while there are several investigational agents in the clinic for narcolepsy, we do not see any new or novel mechanisms of action coming to the market that will impact the growth of WAKIX until late during its life cycle in this poly pharmacy market. Based on these reasons, along with the vast market opportunity that remains in narcolepsy, we believe that we can continue to grow the franchise for years to come and remain confident that WAKIX represents a $1 billion plus opportunity in adult narcolepsy alone and we are well on our way.

最後，雖然臨床上有幾種治療發作性睡病的研究藥物，但我們沒有看到任何新的或新穎的作用機制進入市場，從而影響WAKIX 的增長，直到其在這個多藥房市場的生命週期後期。基於這些原因，加上嗜睡症領域仍然存在巨大的市場機會，我們相信我們可以在未來幾年繼續發展該系列產品，並堅信WAKIX 僅在成人嗜睡症領域就代表了10 億美元以上的機會，我們在這方面表現良好我們的方式。

This is evidenced by our net revenue guidance for 2024, ranging from $700 million to $720 million. In addition to our strong commercial performance, we also advanced and expanded our clinical development enterprise on several fronts. Kumar will provide more details on our clinical development programs later in the call, but first, let me highlight some of our progress starting with pediatric narcolepsy. We are pleased that FDA granted priority review for our sNDA for WAKIX. This expedites the review process and FDA has set up PDUFA date of June 21. We look forward to collaborating with the agency to potentially introduce a new nonscheduled treatment option for pediatric patients living with narcolepsy.

我們對 2024 年淨收入的指導（從 7 億美元到 7.2 億美元不等）就證明了這一點。除了強勁的商業業績外，我們還在多個方面推進和擴大了我們的臨床開發業務。庫馬爾將在稍後的電話會議中提供有關我們臨床開發計劃的更多詳細信息，但首先，讓我強調一下我們從兒科發作性睡病開始的一些進展。我們很高興 FDA 授予我們 WAKIX 的 sNDA 優先審查權。這加快了審查過程，FDA 將 PDUFA 日期定為 6 月 21 日。我們期待與該機構合作，為患有發作性睡病的兒科患者引入一種新的非定期治療方案。

Turning to idiopathic hypersomnia or IH. After completing our review of the full dataset, we continue to believe that based on the totality of the data, along with pitolisant receiving orphan drug designation for IH and against the backdrop of only one currently approved product that there is a strong case to be made regarding the overall benefit risk proposition of pitolisant for patients with IH. We will be engaging with the agency with this goal in mind, have a meeting scheduled with them next month and look forward to working with the agency on bringing a potential new nonscheduled treatment option, the patients living with IH.

轉向特發性嗜睡症或 IH。在完成對完整數據集的審查後，我們仍然相信，基於數據的整體性，以及 Pitolisant 獲得 IH 孤兒藥指定，並且在當前僅批准一種產品的背景下，有充分的理由關於pitolisant對IH患者的整體獲益風險主張。我們將帶著這個目標與該機構合作，安排下個月與他們舉行會議，並期待與該機構合作，為 IH 患者提供潛在的新的非定期治療選擇。

Our current lifecycle management programs for pitolisant, which include IH, Prader-Willi syndrome, and type one myotonic dystrophy represent about 100,000 diagnosed patients in the US. So if successful, these new indications could contribute up to an additional $1 billion of revenue to the WAKIX franchise. Given in pitolisant's novel mechanism of action and the success of WAKIX in the market, we've been working on Next-Gen formulations at pitolisant with the goal to generate new IP and extend the pitolisant franchise out beyond 2014. These programs entered the clinic last quarter, and we are on track to report PK data in the first half of this year.

我們目前的pitolisant生命週期管理計畫（包括IH、普瑞德威利症候群和一型強直性肌肉營養不良症）代表了美國約10 萬確診患者。因此，如果成功，這些新適應症可能會為 WAKIX 特許經營業務額外貢獻 10 億美元的收入。鑑於pitolisant的新穎作用機制和WAKIX在市場上的成功，我們一直致力於pitolisant的下一代配方，目標是產生新的IP並將pitolisant的特許經營權延伸到2014年後。這些項目於上季進入臨床，我們預計在今年上半年報告 PK 數據。

Another key component of our growth strategy is business development to expand our pipeline beyond WAKIX and diversify our portfolio beyond sleep wake. The Zynerba acquisition, which closed last October, represented an important step in that direction and was an excellent strategic fit for Harmony, bringing in two late-stage development programs focused on orphan rare neuro psychiatric disorders with significant unmet medical needs.

我們成長策略的另一個關鍵組成部分是業務發展，以將我們的產品線擴展到 WAKIX 之外，並使我們的產品組合多元化到睡眠喚醒之外。去年10 月完成的Zynerba 收購代表了朝這個方向邁出的重要一步，對於Harmony 來說是一個極好的戰略契合，引入了兩個後期開發項目，重點關注醫療需求未得到滿足的孤兒罕見神經精神疾病。

And we are not stopping with the Zynerba acquisition and remain very active in business development, continually assessing the BD landscape with a focus on rare neurological disease assets and other rare disease assets with unmet medical needs where we can leverage our existing infrastructure and synergies across our organization. We are looking for assets across a range of development stages with a preference for late-stage assets, but open to early-stage assets where there was a strategic fit. With approximately $426 million in cash, cash equivalents and investments at year end, we are in a solid financial position to execute on BD opportunities, which is a strategic priority for us.

我們不會停止對Zynerba 的收購，並在業務發展方面保持非常積極的態度，不斷評估BD 格局，重點關注罕見神經疾病資產和其他醫療需求未得到滿足的罕見疾病資產，我們可以利用我們現有的基礎設施和跨部門的協同效應。組織。我們正在尋找跨越一系列發展階段的資產，優先考慮後期資產，但對具有策略契合度的早期資產持開放態度。截至年底，我們擁有約 4.26 億美元的現金、現金等價物和投資，財務狀況良好，可以執行 BD 機會，這是我們的戰略重點。

In conclusion, I am proud of our team's accomplishments in 2023 and what we were able to do to help patients living with narcolepsy while advancing our development programs in other rare disease patient populations. We experienced solid and durable growth in our core commercial business, strong momentum in our clinical development programs, and expansion and diversification of our pipeline assets. Based on the dedication and commitment across our organization, I am very excited for our opportunities in 2024. As we remain focused on developing and commercializing innovative treatments for patients living with rare neurological diseases who have unmet medical needs.

總之，我為我們團隊在 2023 年取得的成就以及我們為幫助發作性睡病患者所做的努力感到自豪，同時推進我們在其他罕見疾病患者群體中的開發項目。我們的核心商業業務實現了穩健而持久的成長，臨床開發項目的強勁勢頭以及管道資產的擴張和多元化。基於我們整個組織的奉獻和承諾，我對 2024 年的機會感到非常興奮。我們仍然專注於為醫療需求未被滿足的罕見神經系統疾病患者開發和商業化創新療法。

I will now turn the call over to Jeffrey Dierks, our Chief Commercial Officer, to provide more details on our commercial performance. Jeff?

我現在將把電話轉給我們的商務長 Jeffrey Dierks，以提供有關我們商業業績的更多詳細資訊。傑夫？

Thank you, Jeff. 2023 was a strong year of growth for WAKIX in year four of our commercialization in adult narcolepsy. The fourth quarter represented the strongest revenue quarter in our history with continued growth and momentum in our underlying business fundamentals and top line performance metrics. Net revenue for the fourth quarter was $168.4 million, representing 31% growth from the same quarter prior year and our second consecutive quarter of over $150 million in net revenue.

謝謝你，傑夫。 2023 年是 WAKIX 強勁成長的一年，也是我們成人發作性睡病商業化的第四年。第四季是我們史上最強勁的營收季度，我們的基本業務基本面和頂線績效指標持續成長和勢頭強勁。第四季淨收入為 1.684 億美元，比去年同期成長 31%，也是我們連續第二季淨收入超過 1.5 億美元。

Full year 2023 net revenue was $582 million, a 33% increase from full year 2022. We continue to see strong double digit growth in net revenue for WAKIX heading into year five of our commercialization, reflecting continued high interest of WAKIX in the narcolepsy market. The solid performance and continued growth reinforces our long-term belief that WAKIX represents a potential $1 billion plus opportunity in adult narcolepsy alone.

2023 年全年淨收入為 5.82 億美元，較 2022 年全年成長 33%。進入商業化第五年，我們繼續看到 WAKIX 的淨收入強勁兩位數成長，反映出 WAKIX 對嗜睡症市場持續的高度興趣。穩健的業績和持續的成長增強了我們的長期信念，即 WAKIX 僅在成人嗜睡症領域就代表著 10 億美元以上的潛在機會。

I'd like to share a few key highlights from our performance in the fourth quarter on slide 5. The average number of patients on WAKIX in the fourth quarter increased to approximately 6,150, an increase of approximately 350 average patients sequentially from what we reported last quarter. The impressive growth in average patients in the fourth quarter was driven by strong top line demand and new patient starts and speaks to continued product adoption. And more importantly, it highlights the remaining large diagnosed patient opportunity that we continue to tap into each quarter as the market allows.

我想在投影片 5 上分享我們第四季業績的一些關鍵亮點。第四季 WAKIX 的平均病患數量增加至約 6,150 名，比我們上季報告的平均病患數量連續增加約 350 名。第四季度平均患者數量的令人印象深刻的增長是由強勁的收入需求和新患者的開始推動的，這也說明了產品的持續採用。更重要的是，它凸顯了我們在市場允許的情況下每季繼續利用剩餘的大型診斷患者機會。

In addition to the strong growth in average number of patients on WAKIX, we also saw continued product adoption of WAKIX by the narcolepsy health care community, both in new and existing prescribers. The number of unique prescribers of WAKIX increased again in the fourth quarter. And importantly, we continue to see growth in product adoption of weeks in the prescriber base beyond oxybate REMS enrolled health care professionals. Of the approximately 5,000 health care professionals not enrolled in the oxybate REMS program, more than 30% of them have prescribed WAKIX to date, up from 25% reported in our last earnings call.

除了 WAKIX 患者平均數量的強勁增長之外，我們還看到發作性睡病醫療保健界（無論是新處方者還是現有處方者）繼續採用 WAKIX 產品。WAKIX 的獨立處方者數量在第四季度再次增加。重要的是，我們繼續看到，除了註冊了 oxybate REMS 的醫療保健專業人員之外，處方者群體中產品的採用率在數週內持續增長。在約 5,000 名未參加 oxybate REMS 計畫的醫療保健專業人員中，其中超過 30% 迄今已開出 WAKIX，高於我們上次財報電話會議報告的 25%。

In addition to the continued growth of our prescriber base, we also saw strong growth in the depth of prescribing within the approximately 4,000 oxybate REMS enrolled health care professionals. Our ability to reach and educate the broad narcolepsy treating health care professional universe allows us to access the full diagnosed adult narcolepsy patient opportunity and gives us confidence in continued growth for WAKIX.

除了我們的處方者基礎持續成長之外，我們還看到約 4,000 名註冊了 oxybate REMS 的醫療保健專業人員的處方深度強勁增長。我們有能力接觸和教育廣泛的嗜睡症治療醫療保健專業人士，這使我們能夠獲得全面診斷的成人嗜睡症患者的機會，並使我們對 WAKIX 的持續增長充滿信心。

The availability of new and generic oxybate hasn't impacted patient or prescriber growth or existing strong payer coverage for WAKIX, given its meaningfully differentiated product profile. WAKIX remains the first and only FDA-approved treatment for EDS and cataplexy in narcolepsy that is not scheduled as a controlled substance and attribute that continues to appeal for a broader narcolepsy health care professional audience and patient population, and is a driver of brand growth.

鑑於其顯著差異化的產品概況，新型仿製藥羥丁酯的上市並沒有影響患者或處方者的成長，也沒有影響 WAKIX 現有的強大支付者覆蓋範圍。WAKIX 仍然是第一個也是唯一一個獲得FDA 批准的治療嗜睡症EDS 和猝倒症的藥物，該藥物未被列為受管制物質和屬性，繼續吸引更廣泛的嗜睡症醫療保健專業受眾和患者群體，並且是品牌成長的驅動力。

In summary, 2023 was another year of strong commercial performance for WAKIX. Full year net revenue of $582 million, 33% growth versus the full year 2022. The fourth quarter represented the strongest revenue quarter for Harmony to date with over $168 million in net revenue. The average number of patients on WAKIX increased to approximately 6,150. The WAKIX prescriber base within and beyond the oxybate REMS enrolled health care professional audience continued to grow. And lastly, payer coverage remained strong, even with the availability of new and generic oxybate options. WAKIX continues to demonstrate durable growth in the narcolepsy market. We've seen growth in patients and prescribers every quarter since launch, even with branded and generic treatment availability and new launches during its first four years on the market.

總而言之，2023 年是 WAKIX 商業表現強勁的一年。全年淨收入達 5.82 億美元，較 2022 年全年成長 33%。第四季是 Harmony 迄今為止營收最強勁的季度，淨收入超過 1.68 億美元。使用 WAKIX 的患者平均人數增加至約 6,150 人。加入 oxybate REMS 的醫療保健專業受眾內外的 WAKIX 處方者群體持續成長。最後，即使有新的和通用的羥丁酸鹽選擇，付款人覆蓋率仍然強勁。WAKIX 在嗜睡症市場中持續展現出持久成長的勢頭。自推出以來，我們每個季度都看到患者和處方者數量的增長，即使是品牌和仿製藥的可用性以及上市前四年的新產品也是如此。

Looking ahead to 2024, we expect continued growth in the underlying business fundamentals for WAKIX, with net revenues expected to be between $700 million and $720 million. We anticipate a similar quarterly rhythm to our business in 2024 with what we've experienced in previous years. Traditional seasonal payer dynamic headwinds that impact the entire industry as a whole in Q1, tailwinds coming out of Q1 and Q2 with stronger prescription demand, typical seasonal headwinds in Q3 with lower patient visits that are common for all products and diseases that are chronically managed, and tailwinds in the fourth quarter as we close out the year.

展望 2024 年，我們預期 WAKIX 的基本業務基本面將持續成長，淨收入預計將在 7 億至 7.2 億美元之間。我們預計 2024 年我們的業務季度節奏將與前幾年類似。傳統的季節性付款人動態逆風在第一季度影響整個行業，第一季和第二季出現的順風是處方需求更強，第三季度典型的季節性逆風是患者就診量減少，這對於所有長期管理的產品和疾病來說都很常見，當我們結束這一年時，第四季將迎來順風車。

With no new competition expected in 2024 and limited differentiation in generic and branded products in the near term pipeline, coupled with the large remaining diagnosed patient opportunity, unmet need and the poly pharmacy nature of the narcolepsy market, WAKIX is well positioned for continued growth. Our ability to educate the broad REMS and non-REMS narcolepsy, treating health care professional audience and ability to tap into the full diagnosed patient opportunity gives us confidence in the long-term potential for the brand to represent a $1 billion plus opportunity in adult narcolepsy alone.

由於預計2024 年不會出現新的競爭，且短期內仿製藥和品牌產品的差異化有限，再加上剩餘的大量診斷患者機會、未滿足的需求以及發作性睡病市場的多藥房性質，WAKIX處於持續成長的有利地位。我們有能力教育廣泛的REMS 和非REMS 發作性睡病，治療醫療保健專業受眾，以及利用全面診斷的患者機會的能力，使我們對該品牌在成人發作性睡病方面代表10 億美元以上機會的長期潛力充滿信心獨自的。

Our commercial business has been resilient, and I appreciate the dedication and impact of the entire commercial team and the passion that they have for the narcolepsy patient community.

我們的商業業務一直保持彈性，我很欣賞整個商業團隊的奉獻精神和影響力以及他們對嗜睡症患者群體的熱情。

I would like to now turn the presentation over to Kumar Budur, our Chief Medical Officer, to provide an update on our clinical development pipeline. Kumar?

我現在想將演示轉交給我們的首席醫療官 Kumar Budur，以提供我們臨床開發管道的最新資訊。庫馬爾？

Thank you, Jeff. Last year was a defining year for Harmony R&D. We made great progress in advancing expanding, and diversifying our portfolio working on nine different development programs across five different assets, several of which are in late-stage development. It is not just the numbers, but also the complexity of the program as we target a broad set of indications in rare disease patient population with significant unmet medical need.

謝謝你，傑夫。去年是 Harmony 研發的決定性一年。我們在推動投資組合擴張和多元化方面取得了巨大進展，致力於五項不同資產的九個不同開發項目，其中一些項目正處於後期開發階段。這不僅僅是數字，而且是該計劃的複雜性，因為我們的目標是醫療需求未滿足的罕見疾病患者群體的廣泛適應症。

As we grew our portfolio, we also built a strong, experienced, and dedicated R&D organization ready to take on new opportunities as we continue to build our existing portfolio with new assets we have business developed. I'm proud of the work that our team does every day and we look forward to delivering potential new treatment options for patients with rare diseases with high unmet need. Our full clinical development pipeline is shown on slide number seven.

隨著我們產品組合的發展，我們也建立了一個強大、經驗豐富且專注的研發組織，準備好迎接新的機遇，同時我們繼續利用我們業務開發的新資產來建立現有的產品組合。我為我們團隊每天所做的工作感到自豪，我們期待為需求未被滿足的罕見疾病患者提供潛在的新治療選擇。我們完整的臨床開發流程如第七張投影片所示。

Starting with pediatric narcolepsy, we submitted a supplemental NDA to the FDA for an indication in pediatric narcolepsy in the fourth quarter, and we are pleased with the FDA's decision to grant a priority review. This deficient highlights the need for new treatment option for the approximately 4,000 pediatric patients living with narcolepsy. FDA have set a PDUFA date of June 21. We look forward to working with the FDA to potentially bring a non-scheduled treatment option administered once a day in the morning for pediatric patients with narcolepsy.

從小兒發作性睡病開始，我們在第四季度向 FDA 提交了一份補充新藥申請，用於小兒發作性睡病適應症，我們對 FDA 授予優先審查的決定感到高興。這項缺陷凸顯了約 4,000 名發作性睡病兒科患者需要新的治療選擇。FDA 已將 PDUFA 日期定為 6 月 21 日。我們期待與 FDA 合作，為患有發作性睡病的兒科患者提供每天早上一次的非預定治療方案。

Moving on to our development program in idiopathic hypersomnia. We completed our review of the full dataset and submitted an FDA meeting request in the fourth quarter to discuss the path forward and the meeting is scheduled for March. We are optimistic that we'll be able to find an efficient path forward to bring pitolisant to patients with idiopathic hypersomnia. Our optimism is based on the totality of the data, which strongly supports pitolisant efficacy in patients with idiopathic hypersomnia, especially in the context of high unmet need, with only one (inaudible), which is scheduled controlled substance with a REMS program and the off-label use of Class 2 control stimulants with significant safety issue.

繼續我們的特發性嗜睡症開發計劃。我們完成了對完整數據集的審查，並在第四季度提交了 FDA 會議請求，以討論前進的道路，會議定於 3 月舉行。我們樂觀地認為，我們將能夠找到一種有效的途徑，為特發性嗜睡症患者提供匹托利桑。我們的樂觀是基於全部數據，這些數據強烈支持皮托利桑對特發性嗜睡症患者的療效，特別是在需求高度未得到滿足的情況下，只有一種（聽不清楚），這是透過REMS 計劃安排的受管制物質，並且關閉- 標籤使用具有重大安全問題的 2 類控制興奮劑。

The data from the open-label part of the study, double-blind randomized withdrawal part of the study, and the ongoing long-term extension study in conjunction with the benign safety profile offer a strong benefit proposition in favor of pitolisant or patients with idiopathic hypersomnia. We look forward to engaging with the FDA in a meeting scheduled next month and making a strong case for a positive benefit-risk profile for pitolisant in idiopathic hypersomnia. We will provide further updates on the IH program at our next earnings call.

來自該研究的開放標籤部分、該研究的雙盲隨機退出部分以及正在進行的長期擴展研究的數據與良性安全性相結合，為匹托利桑或特發性患者提供了強有力的益處主張嗜睡症。我們期待在下個月舉行的會議上與 FDA 合作，並為匹托利桑治療特發性嗜睡症的積極獲益風險狀況提供強有力的證據。我們將在下次財報電話會議上提供有關 IH 計劃的進一步更新。

Prader-Willi syndrome, we are on track to initiate the Phase 3 TEMPO study in the first quarter of this year. This will be a global double-blind, randomized placebo-controlled study that will randomize approximately 134 patients to either development or placebo in a 1:1 ratio. The duration of the double-blind treatment period is 11 weeks. The age range is six years and older and the primary endpoint is change in seasonality effect for daytime sleepiness as measured by from FRI team core from baseline to the end of the double-blind treatment period compared to placebo.

Prader-Willi 綜合徵，我們預計在今年第一季啟動 TEMPO 3 期研究。這將是一項全球雙盲、隨機安慰劑對照研究，將以 1:1 的比例將約 134 名患者隨機分為開發組或安慰劑組。雙盲治療期的持續時間為11週。年齡範圍為六歲及以上，主要終點是與安慰劑相比，FRI 團隊核心從基線到雙盲治療期結束時對日間嗜睡的季節性影響的變化。

Based on the promising data from the Phase 2 proof-of-concept study, we are also evaluating the irritable and disruptive behaviors which are common in PWS. This Phase 3 registration study is designed not just to meet the requirements for an indication in PWS, but also fulfill one of the two requirements to gain pediatric exclusivity. We remain confident and committed to gaining pediatric exclusivity for WAKIX which will offer an additional six-month regulatory exclusivity on the back end of the market's clinical sites. Based on the discussions with the FDA, we have a clear line of sight on the requirements for PWR which include data in pediatric narcolepsy patient and data from the Phase 3 study in PWS.

基於第二階段概念驗證研究的有希望的數據，我們也正在評估 PWS 中常見的煩躁和破壞性行為。這項 3 期註冊研究的設計不僅是為了滿足 PWS 適應症的要求，而且還滿足獲得兒科特許經營權的兩個要求之一。我們仍然有信心並致力於獲得 WAKIX 的兒科獨家經營權，這將為市場臨床站點的後端提供額外六個月的監管獨家經營權。根據與 FDA 的討論，我們對 PWR 的要求有了清晰的認識，其中包括兒科發作性睡病患者的數據和 PWS 3 期研究的數據。

We are making steady progress to meet this requirement for pediatric narcolepsy sNDA submission in the fourth quarter and the initiation of Phase 3 PWS studied in this quarter are designed to support our efforts to gain pediatric exclusivity for WAKIX. In myotonic dystrophy type one or DM1, we were pleased to report positive top line results from the Phase two proof of concept study, where we saw clinically meaningful improvements in not just excessive daytime sleepiness as measured by the daytime sleepiness scale, but also in fatigue which was assessed using fatigue, severity scale. And these data are summarized on slide 9.

我們正在穩步取得進展，以滿足第四季度提交兒科發作性睡病 sNDA 的要求，並在本季度啟動 PWS 3 期研究，旨在支持我們為獲得 WAKIX 兒科獨家權利而做出的努力。在強直性肌肉營養不良一型或DM1 中，我們很高興地報告第二階段概念驗證研究的積極頂線結果，其中我們不僅看到了具有臨床意義的改善，不僅通過日間嗜睡量表測量的日間過度嗜睡，而且在疲勞方面也有臨床意義的改善使用疲勞、嚴重程度量表進行評估。這些數據在投影片 9 中進行了總結。

It's important to note that these two symptoms, excessive daytime sleepiness and fatigue at present in approximately 80% to 90% of patients currently on DM1, and these symptoms are the acid (inaudible), are the core symptoms of myotonia and focusing on the weakness. A clear and consistent dose response was also demonstrated with the higher dose showing the greater response than the lower dose across the study endpoints.

值得注意的是，目前正在接受DM1 治療的患者中，約有80% 至90% 的患者出現白天過度嗜睡和疲勞這兩種症狀，而這些症狀是酸（聽不清楚），是肌強直的核心症狀，重點是無力。 。也證明了清晰且一致的劑量反應，在整個研究終點中，較高劑量比較低劑量顯示出更大的反應。

In addition, the safety profile in this patient population is consistent with the established safety profile of pitolisant. We are currently reviewing the complete dataset to assess the opportunity and inform our next steps. As we have noted in the past, this is an indication which could be pivoted to the extent of pitolisant-based formulation, which will have a much longer patent on a day.

此外，該患者群體的安全性與 Pitolisant 既定的安全性一致。我們目前正在審查完整的數據集，以評估機會並為我們的下一步提供資訊。正如我們過去所指出的，這是一個可以轉向基於pitolisant的製劑範圍的跡象，該製劑將擁有更長的專利。

We continue to make good progress on the Next-Gen pitolisant-based formulation, NG1 and NG2 with our partner Biome Project, with a goal of generating new IP, extending the pitolisant franchise beyond 2040, and bringing new treatment options for people living with rare diseases. Please note, we have updated the naming conventions for these two formulations according to this expected market entry timing. Next-Gen 1 or NG1 is a modified formulation of pitolisant with a potential for clinical differentiation and a fast-to-market strategy based on the demonstration of bio equivalence.

我們與我們的合作夥伴Biome Project 繼續在下一代基於pitolisant的製劑NG1和NG2方面取得良好進展，目標是產生新的智慧財產權，將pitolisant的特許經營權擴展到2040年以後，並為罕見疾病患者帶來新的治療選擇疾病。請注意，我們已根據預期的市場進入時間更新了這兩種配方的命名約定。Next-Gen 1或NG1是pitolisant的改良製劑，具有臨床分化潛力和基於生物等效性證明的快速上市策略。

We expect to launch NG1 with integrated lifecycle, Nex-Gen 1 or NG2, is an enhanced formulation of pitolisant designed to deliver an optimized PK profile and a higher dosage front. This formulation will have a new IP, a full clinical development program and is expected to be launched towards the end of mid-to-late cycle. Both formulation, NG1 and NG2 entering the clinic in the fourth quarter, and we expect PK data on both of them in the first half of this year. We were also pleased to expand and diversify our pipeline last quarter with the acquisition of Zynerba. This brought in ZYN002 of pharmaceutically produced synthetic cannabidiol, devoid of PSC for customer delivery, which like WAKIX represents another portfolio of product opportunities.

我們預計將推出具有整合生命週期的 NG1（Nex-Gen 1 或 NG2），它是 pitolisant 的增強配方，旨在提供優化的 PK 曲線和更高的劑量前緣。該製劑將擁有新的IP、完整的臨床開發計劃，預計將在中後期週期末推出。NG1和NG2這兩種製劑均於第四季進入臨床，我們預計今年上半年將獲得這兩種製劑的PK數據。上季我們也很高興透過收購 Zynerba 來擴大和多元化我們的產品線。這引入了製藥生產的合成大麻二酚 ZYN002，不含 PSC 供客戶交付，這與 WAKIX 一樣代表了另一種產品機會組合。

We are currently enrolling patients in pivotal Phase 3 pivotal trial in Fragile X syndrome and are very excited about this opportunity. There are approximately 80,000 patients diagnosed with Fragile X syndrome in the US with no approved treatments and significant unmet medical need. We had an opportunity to assess the timeline of the pivotal trial and expect to complete patient enrollment in the first quarter of 2025 with the topline data in mid-2025.

我們目前正在招募參加脆性 X 症候群關鍵 3 期關鍵試驗的患者，我們對這個機會感到非常興奮。在美國，大約有 80,000 名患者被診斷出患有脆性 X 綜合徵，但尚未獲得批准的治療方法，且醫療需求顯著未被滿足。我們有機會評估關鍵試驗的時間表，並預計在 2025 年第一季完成患者入組，並在 2025 年中期獲得頂線數據。

ZYN002 was also studied in an open-label Phase 2 proof-of-concept study in patients with 22q deletion syndrome, known as the INSPIRE trial, which generated promising data. This represents another market opportunity of approximately 80,000 patients in Europe, and we have been interacting with FDA our Phase 3 program in 22q. It is worth noting that ZYN002 is the global opportunity for Harmony, and we look forward to exploring this opportunity to bring this novel treatment to people living with Fragile X syndrome and 22q around the world.

ZYN002 也在一項針對 22q 缺失症候群患者的開放標籤 2 期概念驗證研究（稱為 INSPIRE 試驗）中進行了研究，該試驗產生了有希望的數據。這代表著歐洲約 80,000 名患者的另一個市場機會，我們在 22 季一直在與 FDA 就我們的 3 期專案進行互動。值得注意的是，ZYN002是 Harmony 的全球機會，我們期待探索這個機會，將這種新穎的治療方法帶給世界各地的脆性 X 綜合徵和 22q 患者。

To conclude, we have made great progress at Harmony in advancing, expanding, and diversifying our portfolio, resulting in a pipeline with multiple late-stage programs. I look forward to sharing additional updates as we continue to make progress on our clinical development program. On behalf of Harmony, I would like to thank all the patients and their families for participating in our clinical trials as one of the clinical investigators and site personnel for their effort and commitment in helping us to advance our development programs.

總而言之，Harmony 在推進、擴展和多樣化我們的產品組合方面取得了巨大進展，形成了包含多個後期專案的管道。隨著我們的臨床開發計劃繼續取得進展，我期待分享更多更新。我謹代表 Harmony，感謝所有患者及其家人作為臨床研究人員和現場工作人員之一參與我們的臨床試驗，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)，以了解我們財務表現的最新情況。桑迪普？

Thank you, Kumar, and good morning, everyone. This morning we issued our fourth quarter earnings release and filed our 10-K. You'll find the details of our fourth quarter and full year 2023 financial and operating results. Our financial performance is also shown on slides 10 through 13. We finished the year with strong momentum across the business, helping us deliver solid growth across several key metrics. We reported $582 million in annual WAKIX net revenue, achieved our third year of profitability, along with robust cash generation. In addition, we advanced our pitolisant lifecycle management program and executed on business development with the acquisition of Zynerba. We also deployed capital towards our share repurchase program. Overall we remain well positioned to execute on our growth strategy moving forward.

謝謝你，庫馬爾，大家早安。今天早上，我們發布了第四季度收益報告並提交了 10-K。您將找到我們第四季度和 2023 年全年財務和營運業績的詳細資訊。我們的財務表現也顯示在投影片 10 至 13 中。我們以強勁的業務勢頭結束了這一年，幫助我們在幾個關鍵指標上實現了穩健成長。我們公佈的 WAKIX 年度淨收入為 5.82 億美元，第三年實現盈利，並產生了強勁的現金流。此外，我們還推進了 Pitolisant 生命週期管理計劃，並透過收購 Zynerba 來執行業務開發。我們也為股票回購計畫部署了資金。總體而言，我們仍然處於有利位置，可以執行我們的未來成長策略。

So let me take a moment to review our financial results in more detail. For the fourth quarter of 2023, we reported our strongest revenue quarter in company history with net revenues of $168.4 million compared to $128.3 million in the prior year quarter, representing a growth of 31%. Performance in the quarter reflects the strong continued underlying demand for WAKIX. In the fourth quarter of 2023 operating expenses were $85.1 million compared to $53.8 million in the prior year quarter. The higher operating expenses were primarily driven by our advancement of our clinical development programs, including ZYN002 expenses related to the commercialization of WAKIX and one-time Zynerba transaction related costs of $9.8 million.

讓我花點時間更詳細地回顧一下我們的財務表現。2023 年第四季度，我們報告了該公司歷史上最強勁的收入季度，淨收入為 1.684 億美元，而去年同期為 1.283 億美元，成長了 31%。本季的業績反映了對 WAKIX 強勁持續的潛在需求。2023 年第四季的營運費用為 8,510 萬美元，而去年同期為 5,380 萬美元。營運費用增加主要是由於我們臨床開發項目的進展，包括與 WAKIX 商業化相關的 ZYN002 費用以及一次性 Zynerba 交易相關費用 980 萬美元。

Operating income for the fourth quarter of 2023 was $40.2 million compared to $47.6 million in the prior year quarter. Non-GAAP adjusted net income for the fourth quarter of 2023 was $42.8 million or $0.73 per diluted share compared to $61.9 million or $1.01 per diluted share in the prior year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance. Please refer to our press release for a reconciliation of GAAP to non-GAAP results. We ended the year with $425.6 million of cash, cash equivalents, and investment securities on the balance sheet.

2023 年第四季的營業收入為 4,020 萬美元，去年同期為 4,760 萬美元。2023 年第四季非 GAAP 調整後淨利為 4,280 萬美元，即稀釋後每股收益 0.73 美元，去年同期為 6,190 萬美元，即稀釋後每股收益 1.01 美元。我們認為非公認會計準則調整後淨利更能反映了基本業務績效。請參閱我們的新聞稿，以了解 GAAP 與非 GAAP 業績的調整表。年底，我們的資產負債表上有 4.256 億美元的現金、現金等價物和投資證券。

The balance reflects continued strong cash generation with approximately $77 million in cash from operations in the fourth quarter, offset by the Zynerba acquisition costs and share repurchase activities in the quarter. For the full year of 2023, we generated $219 million in cash from operations. During the fourth quarter, we returned capital to shareholders and repurchased approximately 1.8 million shares of common stock for $50 million, bringing the full year total of repurchase activities to 3.2 million shares of common stock for $100 million. Moving forward, we expect to continue to opportunistically repurchase shares under the remaining share repurchase program authorization of $150 million. Our strong balance sheet allows us not only to execute on return of capital, but also maintain financial flexibility to execute on business development.

該餘額反映了持續強勁的現金生成，第四季度營運產生的現金約為 7,700 萬美元，並被本季 Zynerba 收購成本和股票回購活動所抵銷。2023 年全年，我們的營運現金為 2.19 億美元。第四季度，我們向股東返還資本，並以 5,000 萬美元回購了約 180 萬股普通股，使全年回購活動總額達到 1 億美元，達到 320 萬股普通股。展望未來，我們預計將根據剩餘的 1.5 億美元股票回購計畫授權繼續擇機回購股票。我們強大的資產負債表使我們不僅能夠執行資本回報，還能夠保持財務靈活性以執行業務發展。

In the fourth quarter, we closed the acquisition of Zynerba, which was treated as an asset acquisition for accounting purposes. As previously disclosed, we paid approximately $60 million in cash for the closing of the transaction. We received approximately $26 million of cash and $45 million in deferred tax assets from the acquisition and assumed approximately $14 million in liabilities.

第四季度，我們完成了對 Zynerba 的收購，出於會計目的，該收購被視為資產收購。正如先前披露的，我們為完成交易支付了約 6000 萬美元現金。我們從收購中獲得了約 2,600 萬美元的現金和 4,500 萬美元的遞延稅資產，並承擔了約 1,400 萬美元的負債。

Thus, we recorded $2.3 million in ITR and the charge related to the acquisition, along with $7.5 million in one-time restructuring costs. As a result, we were able to acquire two late-stage programs at very attractive deal terms. Going forward, we will recognize considerable operating synergy and expect ongoing incremental costs from the Zynerba development program of approximately $30 million for 2024.

因此，我們記錄了 230 萬美元的 ITR 和與收購相關的費用，以及 750 萬美元的一次性重組成本。因此，我們能夠以非常有吸引力的交易條款獲得兩個後期項目。展望未來，我們將認識到相當大的營運綜效，並預計 2024 年 Zynerba 開發計畫的持續增量成本約為 3,000 萬美元。

Turning to 2024 guidance for the full year, we expect net revenues of $700 million to $720 million. This range reflects our thoughtful and balanced approach to providing guidance for the first time in Company history. It also highlights that we are well on our way towards the $1 billion plus opportunity in adult narcolepsy alone, that we have consistently communicated and remain confident in.

談到 2024 年全年指引，我們預期淨收入為 7 億至 7.2 億美元。這一範圍反映了我們在公司歷史上首次提供深思熟慮和平衡的指導方針。它還強調，僅在成人發作性睡病方面，我們就朝著超過 10 億美元的機會邁進，我們一直對此進行溝通並保持信心。

And finally, I'll comment on seasonality because you think about the pacing of revenue for the first quarter of 2024. We expect to see the typical seasonal dynamics that the industry as a whole experienced each year in Q1, higher gross-to-net deductions due to insurance plans reset, and higher co-pay obligation along with a drawdown in trade inventories.

最後，我將評論季節性，因為您將考慮 2024 年第一季的收入節奏。我們預計整個行業每年第一季都會經歷典型的季節性動態，由於保險計劃重置而導致總淨額扣除額增加，自付款義務增加以及貿易庫存減少。

In conclusion, we're very pleased with our strong financial performance in 2023 and remain well positioned to continue growth in 2024 and beyond. We look forward to leveraging our financial strength as we continue to expand and diversify the portfolio while also returning capital to shareholders via our share repurchase program.

總而言之，我們對 2023 年強勁的財務業績感到非常滿意，並且仍處於有利位置，可以在 2024 年及以後繼續增長。我們期待利用我們的財務實力，繼續擴大投資組合並使其多元化，同時透過股票回購計畫向股東返還資本。

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

說到這裡，我想把電話轉回給傑夫，讓他作結束語。傑夫？

Thank you, Sandip. In summary, Harmony continues to be a growth story as evidenced by the significant progress our team made in 2023. Looking ahead, we see durability in our core business, strong momentum in our development programs, and remain focused on continuing to grow our WAKIX business and helping even more adult patients living with narcolepsy, advancing our pipeline across both our pitolisant and ZYN002 clinical development programs.

謝謝你，桑迪普。總之，Harmony 仍然是一個成長的故事，我們的團隊在 2023 年取得的重大進展就證明了這一點。展望未來，我們看到我們的核心業務具有持久性，我們的開發項目勢頭強勁，並將繼續專注於繼續發展我們的WAKIX 業務，幫助更多患有發作性睡病的成年患者，推進我們的pitolisant和ZYN002 臨床開發專案的產品線。

Working with our partner BioForge on Next-Gen formulations to extend that the pitolisant franchise to help even more patients living with rare neurological diseases, continuing to build out our pipeline through business development to create a robust portfolio of rare disease assets covering all stages of development, and deploying capital to maximize shareholder value through our share repurchase program and business development opportunities. I am excited for what is to come this year and believe that we are poised to accelerate Harmony's growth in 2024.

與我們的合作夥伴BioForge 合作開發下一代配方，擴大Pitolisant 專營權，以幫助更多患有罕見神經系統疾病的患者，繼續透過業務發展建立我們的管道，以創建涵蓋所有發展階段的強大的罕見疾病資產組合，並透過我們的股票回購計劃和業務發展機會部署資本以最大化股東價值。我對今年即將發生的事情感到興奮，並相信我們準備在 2024 年加速 Harmony 的發展。

This concludes our planned remarks for today. Thank you for joining our call, and I will now turn the call back over to the operator to facilitate the Q&A session. Operator, can you please open the call to questions?

我們今天計劃的發言到此結束。感謝您加入我們的通話，我現在將把通話轉回給接線生以方便問答環節。接線員，您能打開提問電話嗎？

Thank you. (Operator Instructions) Ami Fadia, Needham & Company.

謝謝。（操作員說明）Ami Fadia，Needham & Company。

Good morning. Thanks for taking my question, and thank you for giving all the updates from the pipeline. Firstly, I have two questions. First, can you talk about the two new pitolisant formulation on which you're going to be sharing data in the first half? What should we expect to see from the data? And just to set up expectations for investors will we be able to get visibility into how the formulations make it differentiated from WAKIX based on that data?

早安.感謝您提出我的問題，並感謝您提供管道中的所有更新。首先，我有兩個問題。首先，您能談談您將在上半年分享數據的兩種新的皮托利桑製劑嗎？我們應該從數據中看到什麼？為了給投資者設定期望，我們是否能夠根據這些數據了解配方如何使其與 WAKIX 區分開來？

And then the second question is regarding idiopathic hypersomnia. If you could shed any additional color on the analysis that you have put together for your meeting with the FDA? And if you could comment on whether there's any possibility of generating any additional data from the open-label portion of the study to support an approval? Thank you.

第二個問題是關於特發性嗜睡症。您能否對與 FDA 會面而進行的分析進行補充？您是否可以評論是否有可能從研究的開放標籤部分產生任何額外數據以支持批准？謝謝。

Yeah Ami. Good morning. Thank you for your questions, and I'll ask Kumar to comment on the Next-Gen formulations and some visibility there and as well as our preparation for the FDA meeting on IH. Kumar?

是的，阿米。早安.感謝您提出問題，我將請 Kumar 對下一代配方和其中的一些知名度以及我們為 FDA 的 IH 會議所做的準備發表評論。庫馬爾？

Yeah. Good morning Ami. Thanks for the question. In terms of Next-Gen formulations, as we mentioned, we made progress on Next-Gen formulations last year, and we were really pleased to bring both of those two formulations into the clinic in the fourth quarter. And as we've previously said, we will provide data from the Next-Gen formulation in the first half of this year.

是的。早上好，阿米。謝謝你的提問。在下一代配方方面，正如我們所提到的，我們去年在下一代配方方面取得了進展，我們很高興在第四季度將這兩種配方帶入臨床。正如我們之前所說，我們將在今年上半年提供下一代配方的數據。

In terms of Next-Gen 1 or NG1, it's a modified pitolisant formulation with a potential for clinical differentiation fast-to-market strategy by demonstrating bioequivalence alongside a clinical study that will offer a meaningful clinical differentiation for patients. The nature of the clinical study and the potential differentiation that will be offered will be discussed at the next earnings call, along with the PK data. With the Next-Gen2 or NG2 formulation, it's an enhanced formulation of pitolisant designed to deliver optimized PK and also an ability to go to a higher dose strength. This is the formulation that will have a full development program, a new IP, and it will extend the pitolisant franchise well beyond 2014. And we plan to provide the PK data from this formulation at our next earnings call.

就Next-Gen 1或NG1而言，它是一種改良的pitolisant製劑，透過證明生物等效性和臨床研究，具有臨床分化快速上市策略的潛力，為患者提供有意義的臨床分化。臨床研究的性質和將提供的潛在差異化以及 PK 數據將在下一次財報電話會議上討論。Next-Gen2 或 NG2 配方是 Pitolisant 的增強配方，旨在提供優化的 PK，並且能夠達到更高的劑量強度。配方將擁有完整的開發計劃、新的 IP，並將把pitolisant 的特許經營權延伸到 2014 年之後。我們計劃在下次財報電話會議上提供該配方的 PK 數據。

Regarding your question about the idiopathic hypersomnia, Ami the totality of the data from the open-label study, from the randomized withdrawal period of the study, and the long-term extension study, the post pitolisant efficacy in patients with idiopathic hypersomnia. And in terms of file the argument of the discussions that we will be having with the FDA is the totality of the data, the nonscheduled status of the pitolisant, the ease of administration, a relatively benign safety profile, especially in the context of only one plus that it happens scheduled three controlled substance and the off-label use of plus 2.4 (technical difficulty).

關於你關於特發性嗜睡症的問題，Ami 提供了來自開放標籤研究、研究的隨機退出期和長期擴展研究、特發性嗜睡症患者的匹托利尼後療效的全部數據。就文件而言，我們將與 FDA 進行討論的論點是數據的整體性、pitolisant 的非預定狀態、易於管理、相對良好的安全性，特別是在只有一種藥物的情況下。加上它發生了預定的三種受管制物質和標籤外使用加上2.4（技術難度）。

So all these are factors offered a strong benefit risk proposition to bring pitolisant for patients with idiopathic hypersomnia. And we hope to have good discussions with the FDA and find an efficient path forward to bring pitolisant patients with idiopathic hypersomnia as soon as possible.

因此，所有這些因素都為特發性嗜睡症患者使用匹托利桑提供了強有力的益處風險主張。我們希望與 FDA 進行良好的討論，找到一條有效的途徑，盡快為患有特發性嗜睡症的患者帶來 Pitolisant。

Thank you.

謝謝。

Charles Cliff Duncan, Cantor Fitzgerald.

查爾斯·克里夫·鄧肯，坎托·菲茨杰拉德。

Hey, good morning, Jeff and team. Congratulations on a good year in 2023. Thanks for taking our questions. I have one commercial question and then a pipeline question to follow. So regarding the commercial question, absolutely appreciate the 2025 rev guide looks good to me. I note that you've added about 350 patients on WAKIX per quarter for the last three quarters. And that seems to be just a really consistent number. And I guess I'm wondering if you could speak to anything in the market dynamics or prescriber access that results in that 350 or is that just serendipity? Thanks.

嘿，早上好，傑夫和團隊。恭喜您在 2023 年度過了美好的一年。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。因此，關於商業問題，我絕對欣賞 2025 年的轉速指南。我注意到，過去三個季度，您每季度在 WAKIX 上增加了大約 350 名患者。這似乎是一個非常一致的數字。我想我想知道您是否可以談談市場動態或處方者准入方面的任何內容，從而導致 350 的結果，或者這只是機緣巧合？謝謝。

Good morning, Charles. Thank you for your question. Yes, I think, Jeff Dierks can provide some color on the patient ads and the continued market opportunity for WAKIX.

早上好，查爾斯。謝謝你的問題。是的，我認為 Jeff Dierks 可以為患者廣告和 WAKIX 的持續市場機會提供一些色彩。

Sure. Good morning, Charles, and thanks for the question. Yeah, we've been extremely pleased with the durable growth that we've seen in the average number of patients on WAKIX. And I think some of the things that we're seeing, Charles, is given the unique and meaningfully differentiated product profile, WAKIX has the ability and our sales team has the ability to engage with the broad 9,000 approximate health care professionals that see and treat the narcolepsy patients.

當然。早安，查爾斯，謝謝你的提問。是的，我們對 WAKIX 患者平均數量的持續成長感到非常滿意。我認為，Charles，我們看到的一些東西被賦予了獨特且有意義的差異化產品概況，WAKIX 有能力，我們的銷售團隊有能力與大約 9,000 名負責治療和治療的醫療保健專業人員進行接觸發作性睡病患者。

And what that does is that affords us the opportunity to tap into the full diagnosed patient opportunity, both those individuals and healthcare professionals outside the oxybate REMS program, which we continue to see meaningful growth in the number of unique writers every quarter. But even within the oxybate REMS enrolled health care professionals, even with the availability of generic and once-nightly oxybate launches this year, we're seeing meaningful growth -- excuse me, in terms of depth of prescribing in that audience.

這樣做的作用是，使我們有機會利用全面診斷的患者機會，包括 oxybate REMS 計劃之外的個人和醫療保健專業人員，我們每個季度都會看到獨特作家的數量出現有意義的增長。但即使在 oxybate REMS 註冊的醫療保健專業人員中，即使今年推出了仿製藥和每晚一次的 oxybate，我們也看到了有意義的增長——請原諒，就該受眾的處方深度而言。

So I think really what we're seeing is the unique nature of the meaningfully differentiated product profile, the non-scheduled status, the broad clinical utility that Jeff Dayno spoke about. That really affords us the ability to continue to tap into that broad diagnosed patient opportunity as the market allows around or the traditional quarterly dynamics that we speak about each earnings call. But Charles, we're extremely pleased with what we're seeing as I'm hearing from you as well. And we're confident in continued growth in the average number of patients as we move into 2024.

所以我認為我們真正看到的是傑夫戴諾談到的有意義的差異化產品概況的獨特性、非預定狀態以及廣泛的臨床實用性。這確實使我們有能力繼續利用廣泛的診斷患者機會，因為市場允許或我們在每次財報電話會議上談論的傳統季度動態。但是查爾斯，我們對所看到的非常滿意，因為我也收到了你的來信。進入 2024 年，我們對平均患者數量持續成長充滿信心。

Okay. That's helpful. Added color, Jeff. Thanks. A quick question on the pipeline -- actually a multi part question, sorry about that. And that is, appreciate the Phase 3 TEMPO study data or not data -- excuse me details. I'm wondering when you would anticipate data? How rapidly do you think that study can enroll given some competing programs? And then is the NDA, sNDA timing, I assume that would be gated by the open label extension or would you file perhaps before that's completed? And then the second part of the question is regarding the pediatric narcolepsy and priority review, It seems to say something about the agency's perspective on the safety of the product. So I'm wondering if you could provide any thoughts on that and recent priority review being granted?

好的。這很有幫助。添加顏色，傑夫。謝謝。關於管道的一個簡單問題——實際上是一個由多部分組成的問題，對此感到抱歉。也就是說，欣賞第三階段 TEMPO 研究數據或不欣賞數據——請原諒我的細節。我想知道您什麼時候會收到數據？考慮到一些競爭項目，您認為研究的註冊速度有多快？然後是 NDA、sNDA 時間，我認為這將由開放標籤擴充功能來控制，或者您可能會在完成之前提交文件？然後問題的第二部分是關於兒科發作性睡病和優先審查，這似乎說明了該機構對產品安全性的看法。所以我想知道您是否可以對此以及最近授予的優先審查提供任何想法？

Yeah, Charles. First, let me say, I think that we're excited to be initiating the Phase 3 TEMPO study in patients with Prader-Willi. I'll have two more comment on that and then I'll circle back on some thoughts about the priority review for the pediatric narcolepsy sNDA. Kumar?

是的，查爾斯。首先，我想我們很高興能夠在 Prader-Willi 患者中啟動 TEMPO 3 期研究。我對此還有兩點評論，然後我將回顧一些關於兒科發作性睡病 sNDA 優先審查的想法。庫馬爾？

Hey, good morning, Charles. Thanks for the question. Regarding the PWS study, first of all, we are very pleased to have the orphan drug designation from the FDA for PWS program. In terms of recruitment, we anticipate to complete enrollment in about two years. It is true, Charles, that there are multiple programs in this space. But then, we are the only ones who are looking at excessive daytime sleepiness and behavioral, something PWS. The other programs are targeting more towards the hyperphagia in PWS.

嘿，早上好，查爾斯。謝謝你的提問。關於PWS研究，首先，我們很高興能獲得FDA對PWS計畫的孤兒藥資格認定。在招募方面，我們預計在兩年左右完成招生。查爾斯，確實，這個領域有多個項目。但是，我們是唯一關注白天過度嗜睡和行為（PWS）的人。其他項目則更多針對 PWS 患者的食慾過盛。

And as I mentioned previously, more than half of the patients with PWS target 50 daytime sleepiness. And almost all of these patients have behavioral disturbances. And from a proof of concept study, we showed strong data supporting pitolisant efficacy both in excessive daytime sleepiness through September?

正如我之前提到的，超過一半的 PWS 患者的目標是白天嗜睡 50 度。幾乎所有這些患者都有行為障礙。從概念驗證研究中，我們顯示出強有力的數據支持 9 月白天過度嗜睡的皮托利索功效？

Yeah, Charles, can you repeat that second question about the pediatric narcolepsy, sNDA?

是的，查爾斯，您能重複一下關於兒科嗜睡病 sNDA 的第二個問題嗎？

Yes. I mean, the pediatric narcolepsy, PDUFA, and rapid time to respond just seems to say something about the safety of the product or the agency's perspective on that. Not speaking for the agency of course, but that combined with the priority review, I guess. Do you have any thoughts about the perspectives?

是的。我的意思是，小兒發作性睡病、PDUFA 和快速反應時間似乎說明了該產品的安全性或該機構對此的看法。當然不是代表該機構，而是與優先審查相結合，我想。您對觀點有什麼想法嗎？

Yeah, Charles, I mean, what I would say, I think that as we shared this week, we're very pleased with the interactions we've had with FDA with regards to the orphan drug designation for the pitolisant for Prader-Willi and then followed by the decision priority review for the pediatric narcolepsy sNDA. I think that it reflects the -- with regards to the overall benefit risk profile, pitolisant and what we have said all along, and advance the development programs.

是的，查爾斯，我的意思是，我想說的是，我認為正如我們本週分享的那樣，我們對與 FDA 就 Prader-Willi 的pitolisant 的孤兒藥指定進行的互動感到非常滿意然後是兒科發作性睡病sNDA 的決定優先審查。我認為它反映了關於整體利益風險狀況、pitolisant 和我們一直以來所說的，並推進了發展計劃。

We don't have any concerns with regards to the safety profile that has been consistent from the original pivotal development program in narcolepsy and on through the lifecycle management programs that we've been conducting with no real change in the overall safety profile and the favorable benefit risk profile. I think that reflects the positive interactions we've had with the agency, the decision that we've received, and we remain focused on the execution and advancement of those development programs to bring potential new treatment options to those patient populations.

我們對安全狀況沒有任何擔憂，該安全狀況與最初的發作性睡病關鍵開發計劃以及我們一直在進行的生命週期管理計劃保持一致，總體安全狀況和有利的情況沒有真正的變化效益風險狀況。我認為這反映了我們與該機構的積極互動、我們收到的決定，我們仍然專注於這些開發計劃的執行和推進，為這些患者群體帶來潛在的新治療選擇。

Very good. Thanks for the added info. Congrats on a good year.

非常好。感謝您新增的資訊。恭喜你度過了美好的一年。

Thanks, Charles.

謝謝，查爾斯。

François Daniel Brisebois, Oppenheimer.

弗朗索瓦·丹尼爾·布里斯博伊斯，奧本海默。

Hi. Can you hear me okay?

你好。你聽得到我說話嗎？

Yes, yes, right.

是的，是的，沒錯。

Okay. Thanks for taking the question. Just I was just wondering, in terms of the guidance, can you help us understand what the thought process was behind giving guidance for the first time here? And how should we be thinking about the revenues for patients in 2024? Thank you.

好的。感謝您提出問題。我只是想知道，就指導而言，您能否幫助我們了解首次在這裡提供指導背後的思維過程是什麼？我們應該如何考慮 2024 年患者的收入？謝謝。

Thanks, Frank. Sandip.

謝謝，弗蘭克。桑迪普。

Sure. As I -- thanks for the question. I mean, our guidance represents what I'd say it's a thoughtful and balanced approach, especially for the first year, we're giving guidance. I think we certainly have opportunities to providing updates as we go throughout the year with respect to the guidance (multiple speakers).

當然。謝謝你的提問。我的意思是，我們的指導代表了我所說的一種深思熟慮和平衡的方法，特別是在我們提供指導的第一年。我認為我們當然有機會在全年中提供有關指導的最新信息（多個發言者）。

how we should think about pricing or maybe revenues pertaining to (technical difficulty)?

我們應該如何考慮定價或相關收入（技術難度）？

Yeah. I think, we did take a price increase earlier this year of about 7%, a portion of that actually falls through to the bottom line. So I think generally you'll see an impact from that as we go throughout the year. Obviously, in the first quarter there's usually headwinds regarding our gross-to-net pressure and normal.

是的。我認為，今年早些時候我們確實將價格上漲了 7% 左右，其中一部分實際上落入了利潤。所以我認為，總的來說，隨著我們全年的發展，你會看到它的影響。顯然，在第一季度，我們的總淨壓力和正常情況通常會遇到阻力。

Yes, things happen. Typically in the seasonality that happens, you generally don't see as much of that in the first quarter, but generally as we go throughout the year, you'll see the benefit is very similar to the pattern that we've had over the last three, four years.

是的，事情發生了。通常，在發生的季節性中，您通常不會在第一季看到那麼多，但一般來說，隨著我們全年的發展，您會發現收益與我們過去一年的模式非常相似。過去三、四年。

Great. Thank you very much.

偉大的。非常感謝。

Yeah. Thanks, Franc.

是的。謝謝，弗蘭。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Hello. Thanks. So just a couple. First, regarding business development, I wanted to get more detailed thoughts on the extent to which you do a larger scale transaction versus something smaller scale along the lines of Zynerba. Just philosophically, how are you thinking about acquisitions in general? And tied to that question is also would you lever up and lever up significantly to do something? So that's number one. And then number two, I wanted to pick your brain on the orexins. We've seen some data from Takeda, from Alkermes. There are others, of course, I'm wondering to get your view on the potential long-term impact on the orexin 2 receptor agonist to the extent one or more reach the market? Thank you.

你好。謝謝。所以只是一對。首先，關於業務發展，我想更詳細地了解您在多大程度上進行較大規模的交易，而不是像 Zynerba 那樣進行較小規模的交易。從哲學上來說，您整體上如何看待收購？與這個問題相關的是，你是否會加強槓桿來做些什麼？所以這是第一。第二，我想了解你對食慾素的看法。我們已經看到了來自武田（Takeda）和 Alkermes 的一些數據。當然，還有其他藥物，我想知道您對一種或多種進入市場後對食慾素 2 受體激動劑的潛在長期影響有何看法？謝謝。

Yeah. Thanks, David. Good morning. I think with regards to business development, we're assessing the landscape very actively, and we're open to sort of all opportunities with regards to a deal similar to Zynerba, that's a good strategic fit, as well as something more transformational. We're in a strong sort of financial position to transact. So we first look for good strategic fit, prefer sort of late stage assets, but open to earlier stage, and those that can launch both during the WAKIX life cycle and after. In terms of capacity, I'll ask Sandip to comment on that.

是的。謝謝，大衛。早安.我認為在業務發展方面，我們正在非常積極地評估形勢，並且我們對與 Zynerba 類似的交易的所有機會持開放態度，這是一個很好的戰略契合點，也是更具變革性的東西。我們的財務狀況良好，可以進行交易。因此，我們首先尋找良好的策略契合度，更喜歡後期資產，但對早期階段開放，以及那些可以在 WAKIX 生命週期內及之後啟動的資產。在能力方面，我會請桑迪普對此發表評論。

Thanks, Jeff. Yes. Look, we have good financial strength and flexibility to execute on business development. We also have access to debt, if appropriate, as well as the capital markets as also we mentioned we had over $425 million of cash and cash equivalents available. We're generating significant positive cash flow. Last quarter was about $77 million in cash flow generation as well as almost over $219 million last year in cash generation. So I think we have a good flexibility, as Jeff mentioned, to look at both small add-on transactions as well as potentially something that some are larger and transformative. But I think the important thing is the filter that Jeff mentioned upfront in terms of making sure it's a good strategic fit for the company. And I think from a capital perspective, we have broad flexibility.

謝謝，傑夫。是的。看，我們有良好的財務實力和靈活性來執行業務發展。如果合適的話，我們還可以獲得債務以及資本市場，我們也提到我們擁有超過 4.25 億美元的可用現金和現金等價物。我們正在產生大量的正現金流。上一季的現金流量約為 7,700 萬美元，去年的現金流量幾乎超過 2.19 億美元。因此，正如傑夫所提到的，我認為我們有很好的靈活性，可以考慮小型附加交易以及一些可能較大且具有變革性的交易。但我認為重要的是傑夫之前提到的過濾器，以確保它適合公司的策略。我認為從資本角度來看，我們擁有廣泛的靈活性。

Yes. Thanks, Sandip. And David, turning to question about the Orexin agonist, you know this space well on as do we and we're following it closely. So obviously, a lot of attention lately, given some of the data that has come out, I think at a high level, the programs are still early and they are obviously advancing. I think questions are being generated, both from a safety side and the efficacy side, you know, based on the data that has been coming out. Obviously the target is interesting in terms of the next potential novel mechanism of action for narcolepsy and other essential disorders of hypersomlins.

是的。謝謝，桑迪普。大衛，轉向關於食慾素激動劑的問題，你和我們一樣非常了解這個領域，我們正在密切關注它。顯然，最近引起了很多關注，考慮到已經公佈的一些數據，我認為從高水平來看，這些計劃還處於早期階段，而且顯然正在推進。我認為，根據已經發布的數據，從安全性和有效性方面都產生了問題。顯然，就嗜睡症和其他高睡眠素主要疾病的下一個潛在新作用機製而言，該目標很有趣。

So I think we are following the space closely as the data come out as more questions have been generated and I think that they will likely come to market as successful towards the end of the decade towards the end of the WAKIX life cycle. But importantly, it's our belief that narcolepsy will continue to be a poly pharmacy market. New entrants can only help the sales, more share of voice, more education. So interesting novel target I think waits to be seen as these development programs advance and it will continue to be a poly pharmacy market and we'll follow them as things go forward.

因此，我認為隨著數據的出現以及更多問題的產生，我們正在密切關注這個領域，我認為它們很可能會在 WAKIX 生命週期結束的十年末成功上市。但重要的是，我們相信發作性睡病將繼續成為多藥局市場。新進者只能幫助銷售、更多的話語權、更多的教育。我認為隨著這些開發計劃的推進，如此有趣的新目標有待觀察，它將繼續成為一個綜合製藥市場，我們將隨著事情的進展而關注它們。

All right. Thanks.

好的。謝謝。

Thank you.

謝謝。

Thank you. Jason Gerberry, Bank of America.

謝謝。傑森‧格伯里，美國銀行。

Hi guys. Thanks for taking my questions. I'm Sparlon for Jason. Our first question is with regards to Fragile asset. Where are you at with enrollment for the Phase 3 Fragile X syndrome study? And any added clarity as to our assumptions, shape your view on mid-2025 readout timing?

嗨，大家好。感謝您回答我的問題。我是傑森的斯帕隆。我們的第一個問題是關於脆弱資產的。您參加第 3 期脆性 X 症候群研究的情況如何？對於我們的假設是否有任何進一步的明確性，是否可以影響您對 2025 年中期公佈時間的看法？

And then a second commercial question. What are your assumptions for average revenue per rate expansion? Is that a meaningful tailwind for revenue growth in 2024 in your guidance? Or is growth mainly driven by volume? Thank you.

然後是第二個商業問題。您對每次費率擴展的平均收入有何假設？在您的指導中，這對 2024 年收入成長來說是一個有意義的推動力嗎？或者成長主要是由數量驅動的？謝謝。

Thanks for your questions. I'll ask Kumar to comment on the ZYN002 Phase 3 RECONNECT trial. Very exciting opportunity for us and can you provide and then add some more color on where we are there?

感謝您的提問。我將請 Kumar 對 ZYN002 第三階段 RECONNECT 試驗發表評論。對我們來說這是非常令人興奮的機會，您能否提供並為我們所處的位置添加更多色彩？

Yeah. Thank you, Jeff. So we relooked at the timeline as it was previously (inaudible) and based on the historical recruitment plan and the anticipated growth in this particular patient population, we arrived that we will complete the enrollment in the first quarter of 2025, and the top line will be with 2025. Now that the asset is well within [heart], obviously, we will bring all the additional resources and the expertise, not just from a clinical development perspective, but also have the advocacy group as well to plan and accelerate the recruitment.

是的。謝謝你，傑夫。因此，我們重新審視了先前的時間表（聽不清楚），並根據歷史招募計劃和這一特定患者群體的預期增長，我們得出結論，我們將在2025 年第一季完成招募，營收將達到與2025年在一起。既然資產已經在[心中]，顯然，我們將帶來所有額外的資源和專業知識，不僅是從臨床開發的角度來看，還有宣傳小組來規劃和加速招募。

Thanks, Kumar. In terms of revenue per patient, Jeff Dierks, do you want to comment on that?

謝謝，庫馬爾。就每位患者的收入而言，Jeff Dierks，您想對此發表評論嗎？

Sure. So in looking ahead in 2024 question in terms of just price volume or average revenue per patient, at the end of share, we took a 7% price increase in the beginning of the year. And as with previous years, we would expect to capture most of that price increase. And as you're looking at our guidance rate from $700 million to $720 million, you could see that we're expecting 20% plus growth. So you could see the vast majority of the growth we're expecting in 2024 is driven by volume. We've talked a lot about the large remaining diagnosed patient opportunity, the meaningfully differentiated product profile for WAKIX. So we see significant opportunity and room for growth, but hopefully that provides a little bit of context and helps you think about price versus volume assumptions in the average revenue per patient at 2024.

當然。因此，在展望 2024 年的問題時，僅就價格量或每位患者的平均收入而言，在份額結束時，我們在年初將價格上漲了 7%。與前幾年一樣，我們預計將獲得大部分價格上漲。當您查看我們從 7 億美元到 7.2 億美元的指導價時，您會發現我們預計將成長 20% 以上。因此，您可以看到我們預計 2024 年的成長絕大多數是由銷售驅動的。我們已經討論了許多剩餘的診斷患者機會，以及 WAKIX 有意義的差異化產品概況。因此，我們看到了巨大的機會和成長空間，但希望這能提供一些背景信息，並幫助您思考 2024 年每位患者平均收入的價格與數量假設。

Thanks, Jeff.

謝謝，傑夫。

And if I could have one follow-up question. What is the appetite for share buybacks in 2024 look like relative to the $100 million and share buybacks that you guys did in 2023?

我可否再問一個後續問題？與你們在 2023 年進行的 1 億美元股票回購相比，2024 年股票回購的意願如何？

I think as you said, we are looking to take an opportunistic approach. And Sandip, if you want to comment further?

我認為正如你所說，我們正在尋求採取機會主義的做法。Sandip，您想進一步發表評論嗎？

Yeah, look, we were very pleased last year that we were able to do approximately 100 million share repurchase activities over the last couple of quarters. And I think it's really not a question of either or we have the flexibility to do both and respective of business development, we obviously talked about our strategy there. And then in terms of share buyback, again, we'd look at it more opportunistically and at the appropriate levels, we would certainly, in a great cash position to be able to execute. And we have approximately $150 million of capacity still remaining.

是的，看，去年我們非常高興我們能夠在過去幾季進行約 1 億股股票回購活動。我認為這實際上不是一個問題，或者我們可以靈活地進行業務發展和各自的業務發展，我們顯然在那裡討論了我們的策略。然後，在股票回購方面，我們會更加機會主義地看待它，並在適當的水平上，我們當然會擁有大量現金來執行。我們還剩下約 1.5 億美元的產能。

Thank you.

謝謝。

Thank you.

謝謝。

Thank you. Danielle Brill, Raymond James.

謝謝。丹妮爾·布里爾，雷蒙德·詹姆斯。

Hi guys, good morning. Thanks for the questions. I was also hoping you could provide more color on the assumptions that went into your 2024 guidance, specifically around expectations for patient adds. It looks like you're expecting a slowdown in net patient adds each quarter, or are you just being conservative here or is growth starting to moderate? And then as a follow-up, can you remind us what impact the label expansion into the pediatric narcolepsy population will have on the overall tap for WAKIX? Thank you.

嗨，大家早安。感謝您的提問。我還希望您能夠對 2024 年指南中的假設提供更多信息，特別是圍繞對患者的期望。看起來您預計每季的淨新增病患數量會放緩，還是您只是保守，還是成長開始放緩？作為後續行動，您能否提醒我們，標籤擴展到兒科發作性睡病人群將對 WAKIX 的整體市場產生什麼影響？謝謝。

Yeah. Thanks, Danielle, and good morning. Yes, with regards to, I think, in terms of revenue and your revenue guidance and Sandip, do you want to know (multiple speakers)?

是的。謝謝，丹妮爾，早安。是的，我認為，就收入以及您的收入指導和 Sandip 而言，您想知道嗎（多個發言者）？

Yeah. I think as we mentioned, we've taken a thoughtful and balanced approach in terms of providing guidance for the first year and certainly look to provide an update as we go throughout the year. We're not in any way indicating we see great momentum coming out of the fourth quarter and expect that momentum to sort of carry through for the year?

是的。我認為正如我們所提到的，我們在為第一年提供指導方面採取了深思熟慮和平衡的方法，並且當然希望在全年中提供更新。我們沒有以任何方式表明我們看到第四季度出現強勁勢頭並預計這種勢頭會延續到今年？

I mean, Jeff, do you want to comment at all in terms of just overall -- well, for you're saying?

我的意思是，傑夫，你想就整體而言發表評論嗎？嗯，正如你所說？

Sure, Danielle, in terms of looking at it average patient growth and sort of the assumptions in the 2024 guidance. I mean, as you've seen, we've seen demonstrated durable growth in the narcolepsy market, and we've grown average patients every quarter since launch, even with availability. But within that durable growth, that growth has evolved every year and entering our year five of our rare orphan launch, we're going to expect that growth to continue to evolve, that follow the previous year's cadence for the quarterly growth as we tap into that large diagnosed patient opportunity.

當然，丹妮爾，從平均患者增長和 2024 年指南中的假設來看。我的意思是，正如您所看到的，我們已經看到發作性睡病市場的持久增長，並且自推出以來每個季度的平均患者數量都在增加，即使有可用性。但在這種持久的成長中，這種成長每年都在發展，進入我們罕見的孤兒產品推出的第五年，我們預計這種成長將繼續發展，隨著我們利用前一年的季度成長節奏，大量診斷患者的機會。

So you'll see the traditional payer headwinds in the first quarter that impact all brands and specialty products. You'll see the traditional fewer patient visits associated with chronically manage conditions and diseases in Q3. And then typically in previous years, we expect to have the traditional tailwinds in the second and the fourth quarter with stronger prescription demand. Again, but I think the takeaway is we're extremely pleased with what we're seeing, confident in continued growth, and we really believe that WAKIX is well positioned for future growth in 2024. And then your next question on (multiple speakers)

因此，您將在第一季看到傳統的付款人逆風影響所有品牌和特色產品。在第三季度，您將看到與長期管理狀況和疾病相關的傳統患者就診次數減少。通常在前幾年，我們預計第二季和第四季將出現傳統的順風車，處方藥需求將更加強勁。再說一遍，但我認為重點是，我們對所看到的情況非常滿意，對持續成長充滿信心，並且我們確實相信 WAKIX 為 2024 年的未來成長做好了充分準備。然後你的下一個問題是（多個發言者）

It was on pediatric TAM and how that expense going to make its opportunity.

重點是兒科 TAM 以及這筆費用將如何創造機會。

Yeah, I think Jeff can speak to that one. I think, obviously, positive signals from the agency on the importance of that indication in pediatric narcolepsy patients. So Jeff, what does the opportunity look like?

是的，我想傑夫可以和那個人談談。我認為，顯然，該機構發出了關於該適應症對兒科發作性睡病患者重要性的積極信號。那麼傑夫，機會是什麼樣的呢？

So Danielle, we estimate there's about 4,000 pediatric narcolepsy patients in the US. And although it's not a large opportunity, it's an important one. And it's a very underserved patient population. It was only one FDA-approved treatment option being sodium oxybate being a Schedule three REMS product right now. And I think we're very excited about the potential if successful to bring a non-scheduled treatment option, given what we're seeing the impact of narcolepsy on these individuals' lives.

Danielle，我們估計美國約有 4,000 名小兒發作性睡病患者。雖然這不是一個很大的機會，但卻是一個重要的機會。這是一個服務水準非常低的患者群體。目前，羥丁酸鈉是 FDA 批准的唯一治療方案，屬於附表三 REMS 產品。我認為，鑑於我們所看到的發作性睡病對這些人生活的影響，如果成功的話，我們對提供非預定治療方案的潛力感到非常興奮。

Thanks, Jeff. And Danielle, let me just also add with regards to the pediatric narcolepsy, that sNDA, it's also important that those data are we're also pursuing a pediatric exclusivity, which is obviously an important commercial opportunity with regards to an additional six months of regulatory exclusivity. So those data are one component of that, along with the data that we'll be generating in the Phase three Prader-Willi TEMPO study. So both of these components are important and we are advancing both of these and making progress in terms of pediatric narcolepsy data through that submission and then the initiation of the Phase 3 trial in Prader-Willi syndrome. And both of those components are what would be required as we pursue pediatric exclusivity an additional six months of protection.

謝謝，傑夫。Danielle，讓我補充一下關於兒科嗜睡症的 sNDA，這些數據也很重要，我們也在追求兒科獨家權，這顯然是一個重要的商業機會，涉及額外六個月的監管排他性。因此，這些數據以及我們將在第三階段 Prader-Willi TEMPO 研究中產生的數據都是其中的一個組成部分。因此，這兩個部分都很重要，我們正在推進這兩個部分，並透過該提交以及隨後啟動普瑞德-威利症候群的 3 期試驗，在兒科發作性睡病數據方面取得進展。當我們追求兒科專屬性和額外六個月的保護時，這兩個組成部分都是所需要的。

Okay. Thank you so much.

好的。太感謝了。

Thanks, Danielle.

謝謝，丹妮爾。

Thank you. Graig Suvannavejh, Lubrizol.

謝謝。Graig Suvannavejh，路博潤。

Hi. This is Avanci Kavip on for Greg. I just have a question about the one, about the bottleneck opportunities. I know that the timelines have been pushed a little bit due to enrollment, but were there any changes in the trial design as there originally were which also console in?

你好。我是格雷格 (Greg) 的阿萬奇·卡維普 (Avanci Kavip)。我只是有一個關於瓶頸機會的問題。我知道由於註冊的原因，時間表被推遲了一些，但是試驗設計是否與最初的控制台一樣有任何變化？

And then also on the pediatric opportunity, I know you said it's a pretty small opportunity, but do you anticipate growing the WAKIX sales force at all as approved?

然後還有兒科機會，我知道您說過這是一個很小的機會，但您預計會按照批准的方式擴大 WAKIX 銷售隊伍嗎？

Thank you for your question. With regards to the Fragile X study, Kumar?

謝謝你的問題。關於 Fragile X 研究，Kumar？

Yeah, thank you for the question. The Fragile X syndrome, the timeline was not pushed out. As we had mentioned that we will go evaluate the timeline once the asset has been asked, and we had an opportunity to evaluate the timeline. And based on the historical recruitment plan and the anticipated recruitment in this patient population, we arrived at completing enrollment in the first quarter of 2025 with top line anticipated in mid-2025. And there is no change in the study design.

是的，謝謝你的提問。脆性X綜合症，時間表並沒有被推遲。正如我們所提到的，一旦資產被詢問，我們將去評估時間表，並且我們有機會評估時間表。根據歷史招募計畫和該患者群體的預期招募，我們預計在 2025 年第一季完成招募，預計在 2025 年中期實現營收。研究設計沒有變化。

And I would just add, I think that the opportunity is for Harmony for us, if you put our resources towards driving the Phase 3 RECONNECT trial forward with regards to the experience of this clinical development team, about more capacity from an operational perspective and really engaging with the patient community through our patient advocacy efforts as well to drive that forward toward significant market opportunity of 80,000 diagnosed patients in the US.

我想補充一點，我認為Harmony 對我們來說是一個機會，如果您將我們的資源用於推動3 期RECONNECT 試驗的進展，考慮到該臨床開發團隊的經驗，從營運角度來看更多的能力，並且確實透過我們的患者宣傳工作與患者社區互動，並推動這一進程向美國 80,000 名確診患者的重大市場機會邁進。

Turning to pediatric narcolepsy, we see current sort of small market opportunity, but quite an important one. And I think, Jeff sort of alluded to this, an important one in terms of potential new non-scheduled treatment option for pediatric patients with narcolepsy rather than Schedule 2 stimulants. So we are looking forward to working with the agency towards that. And then with regards to the impact on the market opportunity, Jeff?

談到小兒發作性睡病，我們看到目前的市場機會雖小，但卻非常重要。我認為，Jeff 有點提到了這一點，對於患有發作性睡病的兒科患者來說，這是一種潛在的新的非定期治療選擇，而不是附表 2 興奮劑。因此，我們期待與該機構合作實現這一目標。然後關於對市場機會的影響，傑夫？

So in looking at the sales force coverage for pediatric narcolepsy, yeah, we believe that we're optimized for the narcolepsy opportunity with our existing sales force footprint. There will be some new prescribers that we'll be adding to our target list of successful, but we believe that our current team that is very excited about the potential to bring this forward is optimized to be able to take on this new opportunity with these additional patients and with the addition of a handful of health care professionals, there's a high overlap between adult narcolepsy prescribing and pediatric narcolepsy prescribing. So we believe we've got relationships established with a good portion of those prescribers. But we are absolutely optimized with our team and if successful, very excited to bring this new indication forward.

因此，在研究兒科嗜睡症的銷售人員覆蓋範圍時，是的，我們相信我們已經利用現有的銷售人員足跡針對嗜睡症機會進行了優化。我們將把一些新的處方者添加到我們的成功目標名單中，但我們相信，我們目前的團隊對推動這一目標的潛力感到非常興奮，並且經過優化，能夠利用這些新的機會來抓住這一機會。隨著更多的患者和少數醫療保健專業人員的增加，成人發作性睡病處方和兒童發作性睡病處方之間存在高度重疊。因此，我們相信我們已經與其中很大一部分處方者建立了關係。但我們與我們的團隊絕對進行了優化，如果成功，我們將非常高興能夠推出這項新的適應症。

Great. Thanks, Jeff.

偉大的。謝謝，傑夫。

Thank you.

謝謝。

Thank you.

謝謝。

If I can squeeze in one more, sorry. For our gross-to-net, I know you talked about the headwinds in first quarter, but can you just quantify what you think it will be for the full year?

如果我能再擠一張的話，抱歉。對於我們的毛淨值，我知道您談到了第一季的不利因素，但您能否量化一下您認為全年的情況？

Sandip?

桑迪普？

Yes, hi, thanks for the question. As I mentioned, typically in the first quarter across the industry, there, general headwinds from just higher co-pay obligation and insurance funds resets in the first quarter. So we'll see a couple of percentage points impact from that typically what we've seen in the past in the first quarter, and that sort of outcome, again improved as we go throughout the year generally.

是的，嗨，謝謝你的提問。正如我所提到的，通常在整個行業的第一季度，共同支付義務增加和保險基金在第一季重置帶來的普遍阻力。因此，我們將看到過去第一季所看到的幾個百分點的影響，並且隨著我們全年的整體情況，這種結果再次得到改善。

Thank you.

謝謝。

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

謝謝。我沒有再提出任何問題。我現在想將電話轉回給管理階層，讓他們發表結束語。

Thank you, Brittany, and thanks, everyone, for joining our call today and for your interest in Harmony. As you've heard from us this morning, our strong execution in 2023 and solid momentum going into this year. Positioned Harmony well for continued growth in 2024. We look forward to providing updates as we execute on our growth strategy. Thank you and have a great day.

謝謝布列塔尼，感謝大家今天加入我們的電話會議以及對 Harmony 的興趣。正如您今天早上從我們那裡聽到的，我們在 2023 年的執行力強勁，今年勢頭強勁。為 Harmony 在 2024 年的持續成長奠定了良好的基礎。我們期待在執行成長策略時提供最新資訊。謝謝您，祝您有美好的一天。

This does conclude today's Harmony Biosciences' fourth quarter and full year 2023 financial results conference call. You may now disconnect your lines and have a wonderful day.

今天 Harmony Biosciences 第四季和 2023 年全年財務業績電話會議到此結束。您現在可以斷開線路並度過美好的一天。