Harmony Biosciences Holdings Inc (HRMY) 2025 Q2 法說會逐字稿

Good morning. My name is Madison, and I will be your conference operator today. At this time, I would like to welcome everyone to Harmony Biosciences' second-quarter 2025 financial results conference call. (Operator Instructions) Please be advised that today's conference may be recorded. (Operator Instructions)

早安.我叫麥迪遜，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Harmony Biosciences 2025 年第二季財務業績電話會議。（操作員指示）請注意，今天的會議可能會被錄音。（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' second-quarter 2025 financial results and provide a business update. 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 to non-GAAP financial measures. At this stage of our life cycle, we believe non-GAAP financial results better represent the underlying business performance.

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 年第二季的財務業績並提供業務更新。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 on today's 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 and Chief Administrative 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 博士以及首席財務官兼首席行政官 Sandip Kapadia。

As a reminder, we'll 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 thank you for joining our call today. I want to begin today's call by reaffirming something we believe is becoming increasingly clear. Harmony Biosciences is a growth story.

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。在今天的電話會議開始時，我想重申一些我們認為越來越清楚的事情。Harmony Biosciences 是一個成長故事。

We have built something rare in our industry, a profitable, self-funding biotech company with an innovative late-stage pipeline poised to deliver meaningful value for both patients and shareholders. Because of this unique profile, we continue to execute from a position of strength. Our foundational business anchored by WAKIX in narcolepsy has now delivered another quarter of double-digit revenue growth.

我們在產業中建立了罕見的產業，一家獲利且自籌資金的生物科技公司，擁有創新的後期產品線，準備為患者和股東帶來有意義的價值。由於這獨特的特性，我們能夠繼續以優勢地位執行任務。我們以 WAKIX 為基礎的嗜睡症治療業務現已再次實現兩位數的收入成長。

We reported $200.5 million in second-quarter net revenue, representing a 16% increase year over year. This performance extends our four-year streak of profitability and reinforces WAKIX's strong momentum in its 6th year on the market, as reflected by the addition of 400 average patients during the second quarter. WAKIX remains the first and only non-scheduled treatment for narcolepsy, leading to broad clinical utility that is meaningful to both patients and prescribers.

我們報告第二季淨收入為 2.005 億美元，年增 16%。這項業績延續了我們連續四年的獲利勢頭，並鞏固了 WAKIX 上市第六年的強勁勢頭，第二季平均新增患者 400 名就體現了這一點。WAKIX 仍然是第一個也是唯一一個針對嗜睡症的非計劃治療方法，具有廣泛的臨床實用性，對患者和處方者都具有重要意義。

As demonstrated by the sustained momentum, we believe WAKIX will achieve $1 billion-plus blockbuster status in narcolepsy alone, well ahead of loss of exclusivity in 2030. But our story doesn't end with the success of WAKIX, because we are just getting started. What excites us most is what lies ahead.

從持續的發展動能來看，我們相信 WAKIX 僅在嗜睡症治療領域就能取得價值 10 億美元以上的重磅藥物地位，遠早於 2030 年獨佔權的喪失。但我們的故事並沒有隨著 WAKIX 的成功而結束，因為我們才剛開始。最讓我們興奮的是未來會發生什麼事。

Today, Harmony is a multi-franchise company with three core areas of focus sleep/wake, neurobehavioral, and rare epilepsies. Each of these franchises includes late-stage development programs with $1 billion to $2 billion in peak sales potential across multiple indications.

如今，Harmony 是一家擁有多特許經營權的公司，專注於睡眠/覺醒、神經行為和罕見癲癇三個核心領域。這些特許經營權均包括後期開發計劃，在多個適應症中具有 10 億至 20 億美元的峰值銷售潛力。

Let me walk you through what lies ahead in our pipeline, starting with our next major clinical catalyst coming from our neurobehavioral franchise and its innovative investigational product ZYN002. This is a 100% synthetic, pharmaceutically manufactured cannabidiol, devoid of THC delivered through a unique proprietary, patent-protected permeation enhanced transdermal gel formulation.

讓我向您介紹我們未來的產品線，首先是來自我們的神經行為特許經營權及其創新研究產品 ZYN002 的下一個主要臨床催化劑。這是一種 100% 合成、藥物製造的大麻二酚，不含 THC，透過獨特的專有、專利保護的滲透增強透皮凝膠配方輸送。

Our Phase 3 registrational trial in patients with Fragile X syndrome completed enrollment in Q2, and we are on track to report top-line data later this quarter. This study, the RECONNECT study, was designed to confirm the positive findings of the primary outcome from the Phase 2/3 CONNECT study in the pre-specified group of patients with complete methylation of the FMR1 gene, the underlying genetic defect in patients with Fragile X syndrome.

我們針對脆性 X 症候群患者的 3 期註冊試驗已於第二季完成招募，我們將在本季度稍後報告頂線數據。這項名為 RECONNECT 的研究旨在確認 2/3 期 CONNECT 研究在預先指定的 FMR1 基因完全甲基化患者組中的主要結果的積極發現，FMR1 基因是脆性 X 綜合徵患者的潛在遺傳缺陷。

In fact, Fragile X is the most common known inherited cause of intellectual impairment and autism spectrum disorders. Stepping back a moment in order to understand the potential significance of our Phase 3 RECONNECT study. There are roughly 80,000 people living with Fragile X in the US, similar in size to the diagnosed narcolepsy market.

事實上，脆性 X 症候群是已知的導致智力障礙和自閉症譜系障礙最常見的遺傳原因。回顧一下，以了解我們第三階段 RECONNECT 研究的潛在意義。美國約有 8 萬人患有脆性 X 綜合徵，其規模與確診的嗜睡症市場規模相似。

However, unlike that market, there are currently no FDA approved treatments for Fragile X syndrome. A positive readout from the RECONNECT study could represent a major breakthrough. The potential for the first and only approved therapy for Fragile X syndrome, and a transformational moment for people living with Fragile X syndrome and their families who have waited far too long for a therapy designed to address their needs.

然而，與該市場不同的是，目前尚無 FDA 批准的脆性 X 綜合徵治療方法。RECONNECT 研究的正面結果可能代表著一項重大突破。這可能是第一個也是唯一一個獲準的脆性 X 症候群治療方法，對於等待太久、無法得到滿足其需求的治療方法的脆性 X 症候群患者及其家人來說，這是一個轉捩點。

Kumar will be sharing more detail with you on the reasons for our strong conviction in the upcoming top-line data readout. In our sleep/wake franchise, as I mentioned, WAKIX continues to grow, and our pitolisant life cycle management programs are designed to both expand and extend this franchise well into the mid-2040s.

庫馬爾將與您分享更多細節，說明我們對即將公佈的頂線數據充滿信心的原因。正如我所提到的，在我們的睡眠/喚醒特許經營中，WAKIX 繼續增長，我們的 pitolisant 生命週期管理計劃旨在將這一特許經營權擴展並延伸至 2040 年代中期。

We have major catalysts ahead for the two next generation formulations of pitolisant, high dose pitolisant, or pitolisant HD, and a gastro resistant formulation of pitolisant or pitolisant GR. And we are on track to initiate Phase 3 registrational trials in both narcolepsy and idiopathic hypersomnia with pitolisant HD in the fourth quarter of this year.

我們對兩種新一代匹托利桑製劑、高劑量匹托利桑或匹托利桑 HD 以及胃溶性匹托利桑或匹托利桑 GR 有重大催化劑。我們計劃於今年第四季啟動使用 Pitolisant HD 治療發作性睡病和特發性嗜睡症的 3 期註冊試驗。

We are also dancing a novel orexin-2 agonist with a potentially best-in-class profile and remain on track to enter the clinic and initiate first in human studies later this year with clinical data anticipated in 2026. Our third franchise in rare epilepsy is also making steady progress. EPX-100, or clemizole hydrochloride, is one of the most advanced 5HT-2 agonist compounds with a well-characterized mechanism of action and a strong safety record.

我們也正在研發具有潛在同類最佳特性的新型食慾素-2激動劑，並將於今年稍後進入臨床並啟動首次人體研究，預計臨床數據將於 2026 年公佈。我們在罕見癲癇領域的第三個特許經營權也在穩步進展。EPX-100，即鹽酸克立咪唑，是最先進的 5HT-2 激動劑化合物之一，具有明確的功效機制和良好的安全記錄。

It is now in Phase 3 registrational trials for both Dravet syndrome and Lennox-Gastaut syndrome, with pivotal data expected in 2026. Our commitment to patients with serious rare neurological disorders does not end here.

目前，該藥物正處於針對 Dravet 症候群和 Lennox-Gastaut 症候群的 3 期註冊試驗階段，預計 2026 年將獲得關鍵數據。我們對患有嚴重罕見神經系統疾病的患者的承諾不止於此。

To that end, we recently entered into a research collaboration with CiRC Biosciences, a regenerative medicine company discovering novel therapies based on cellular reprogramming, and focused on developing novel regenerative cellular therapies to replace and restore function in patients with advanced neurological disorders.

為此，我們最近與 CiRC Biosciences（一家基於細胞重編程發現新療法的再生醫學公司）開展了研究合作，並專注於開發新型再生細胞療法來替代和恢復晚期神經系統疾病患者的功能。

Our collaboration with CiRC is strategically aligned with our current pipeline and focused on treatments for refractory epilepsy and treatment resistant narcolepsy. This research could potentially result in the next generation of innovative, disease modifying therapies, for these advanced chronic neurological disorders. Sandip will be commenting further on the terms of this deal.

我們與 CiRC 的合作在策略上與我們目前的產品線保持一致，並專注於治療難治性癲癇和難治性發作性睡病。這項研究可能為這些晚期慢性神經系統疾病帶來下一代創新的疾病改良療法。Sandip 將進一步評論該交易的條款。

When you look at Harmony today, it should be evident that what we are building is one of the most robust pipelines in the industry for patients with rare neurological disorders. We now have eight innovative assets across 13 development programs, including up to six Phase 3 trials by the end of this year.

當您今天看到 Harmony 時，您就會明白，我們正在為患有罕見神經系統疾病的患者建立業內最強大的管道之一。目前，我們擁有 13 個開發案中的 8 項創新資產，其中包括今年年底將進行的多達 6 項 3 期試驗。

This pipeline is poised to deliver one or more new product indication launches every year for the next several years. And with more than $670 million in cash and cash equivalents on the balance sheet, and a disciplined approach to capital deployment, we have the flexibility to continue to strategically expand our pipeline through targeted business development efforts in this favorable environment.

未來幾年內，該通路每年都將推出一款或多款新產品。憑藉資產負債表上超過 6.7 億美元的現金和現金等價物，以及嚴謹的資本配置方式，我們可以靈活地在這種有利的環境下，透過有針對性的業務發展努力，繼續策略性地擴大我們的產品線。

So what does all this mean? It means that in an industry where sustainable success remains elusive, Harmony has built something different and something unique: a commercially durable business with a robust late-stage pipeline and a clear path to delivering long-term value for patients, providers, and shareholders alike, and that's what makes harmony one of the most compelling gross stories in biotech today.

那麼這一切意味著什麼？這意味著，在一個可持續成功仍然難以實現的行業中，Harmony 已經建立了一些不同且獨特的東西：一個具有商業持久力的業務，擁有強大的後期管道和為患者、供應商和股東提供長期價值的明確途徑，這就是 Harmony 成為當今生物技術領域最引人注目的故事之一的原因。

With that, I'll turn the call over to Adam Zaeske, our Chief Commercial Officer, for an update on our commercial performance. Adam?

接下來，我將把電話轉給我們的商務長 Adam Zaeske，以了解我們的商業表現的最新情況。亞當？

Thanks, Jeff. Harmony's Q2 2025 results demonstrate the enduring strength of our commercial business. WAKIX delivered $200.5 million in net sales for the quarter, representing 16% year-over-year growth in its 6th year on the market. WAKIX achieved 7,600 average patients in Q2, representing an increase of approximately 400 average patients for the quarter. This represents among the strongest quarterly results we've seen since launch, and continues the steady, reliable growth we've seen for the past several years.

謝謝，傑夫。Harmony 2025 年第二季的業績證明了我們商業業務的持久實力。WAKIX 本季淨銷售額為 2.005 億美元，上市第六年年增 16%。WAKIX 第二季度平均患者人數為 7,600 人，比本季平均患者人數增加了約 400 人。這是我們自推出以來看到的最強勁的季度業績之一，並延續了過去幾年我們看到的穩定、可靠的成長。

This sustained performance is driven by WAKIX's unique position as the only non-scheduled treatment option with its broad clinical utility for the more than 80,000 patients with narcolepsy, as well as the strong focus and execution of our commercial teams with the support of the entire Harmony organization.

這種持續的表現得益於 WAKIX 的獨特地位，即它是唯一一種非計劃治療選擇，對超過 80,000 名嗜睡症患者俱有廣泛的臨床實用性，同時也得益於我們商業團隊在整個 Harmony 組織的支持下的高度關注和執行。

We have a great deal of confidence in the continued growth potential and performance of WAKIX. In addition to its unique position as the only non-scheduled treatment option, WAKIX has among the highest brand awareness in the market, is perceived as efficacious and well tolerated, and is supported by broad payer coverage that has remained consistent for years.

我們對 WAKIX 的持續成長潛力和業績充滿信心。除了作為唯一非計劃治療選擇的獨特地位外，WAKIX 還擁有市場上最高的品牌知名度，被認為有效且耐受性良好，並得到多年來始終如一的廣泛付款人覆蓋的支持。

We see continued increases in prescribing among the approximately 4,000 oxidate rems enrolled, prescribing clinicians. As well as an increase in prescribing and addition of new prescribers with the approximately 5,000 non-oxidate rems enrolled clinicians, where WAKIX is the only branded option. This dual expansion, deepening usage within our core base while broadening our prescriber footprint, demonstrates WAKIX's resilient position and reinforces our confidence in its continued growth trajectory.

我們發現，在約 4,000 名參與 oxidate rems 的處方臨床醫生中，處方量持續增加。隨著處方數量的增加和新處方人員的增加，大約有 5,000 名非氧化物雷姆斯註冊的臨床醫生，其中 WAKIX 是唯一的品牌選擇。這種雙重擴張，深化了我們核心基礎的使用，同時擴大了我們的處方覆蓋範圍，證明了 WAKIX 的彈性地位，並增強了我們對其持續成長軌蹟的信心。

As we look to the second half of 2025, these strong WAKIX fundamentals support our confidence in maintaining its growth momentum. We are confirming our full-year revenue guidance of $820 million to $860 million, and we remain on track to achieve $1 billion-plus in annual revenue in narcolepsy alone.

展望 2025 年下半年，WAKIX 的強勁基本面支撐了我們維持其成長動能的信心。我們確認全年收入預期為 8.2 億美元至 8.6 億美元，我們仍有望僅在嗜睡症治療領域實現 10 億美元以上的年收入。

Looking to the future, the pitolisant GR and HD formulations each target significant unmet patient needs while extending our growth potential with utility patents filed through 2044. Early feedback from physicians and payers on the HD formulation has been particularly encouraging, and we'll be able to fully leverage our commercial infrastructure to drive the next phase of growth through our pitolisant and franchise formulation.

展望未來，pitolisant GR 和 HD 配方分別針對尚未滿足的重大患者需求，同時透過 2044 年提交的實用專利擴展我們的成長潛力。醫生和付款人對 HD 配方的早期回饋特別令人鼓舞，我們將能夠充分利用我們的商業基礎設施，透過我們的 pitolisant 和特許經營配方推動下一階段的成長。

We're also excited for the opportunity to expand beyond the sleep/wale franchise and are eagerly anticipating the top-line data readout for ZYN002 in our neurobehavioral franchise next quarter. Kumar will provide a progress update on these programs in a moment.

我們也很高興有機會擴展到睡眠/睡眠障礙特許經營之外，並熱切期待下個季度我們神經行為特許經營中 ZYN002 的頂線數據讀數。庫馬爾稍後將提供這些計劃的進度更新。

In summary, the fundamentals of our business remain robust. Our strong second-quarter performance reflects the continued execution of our strategic priorities, and we are well positioned to capitalize on the substantial opportunities before us. I'd like to now turn the call over to our Chief Medical and Scientific Officer, Kumar Budur, to discuss the advancements in our clinical development programs. Kumar?

總而言之，我們的業務基本面依然強勁。我們第二季的強勁業績反映了我們持續執行策略重點，並且我們已做好準備，充分利用我們面臨的巨大機會。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. Please refer to the slide number 5 for our pipeline chart. And the clinical development highlights are on slide 6 through slide 11.

謝謝你，亞當。大家早安，感謝大家今天加入我們。請參閱投影片 5 中的管道圖。臨床開發亮點在第 6 張至第 11 張投影片。

In R&D we are on track for our next major catalyst, the top-line data for ZYN002 in Fragile X syndrome in Q3. We have a high degree of confidence and conviction in the success of the Phase 3 registrational trial, the RECONNECT study, as it builds upon the data and insights from the last Phase 2/3 CONNECT study.

在研發方面，我們正按計畫迎接下一個主要催化劑，即第三季 ZYN002 治療脆性 X 症候群的頂線數據。我們對第 3 階段註冊試驗 RECONNECT 研究的成功充滿信心，因為它建立在上一階段 2/3 CONNECT 研究的數據和見解之上。

The efficacy data from the CONNECT study, especially in patients with complete methylation, who accounted for approximately 80% of the patients, is one of the strongest efficacy data sets generated in patients with Fragile X syndrome. We saw over 50% of patients demonstrating clinically meaningful improvements in social avoidance, their primary endpoint, and irritability disruptive behaviors, other core symptoms in patients with Fragile X.

CONNECT 研究的療效數據，特別是在完全甲基化患者中（佔患者總數的約 80%）產生的療效數據，是脆性 X 綜合徵患者中產生的最強療效數據集之一。我們發現超過 50% 的患者在社交迴避（主要終點）和易怒破壞性行為（脆性 X 綜合徵患者的其他核心症狀）方面表現出具有臨床意義的改善。

The RECONNECY study essentially seeks to replicate the statistically significant efficacy signals observed in patients with complete methylation in the CONNECT study with several enhancements to further bolster the probability of success. We have completed enrollment, and we are on track to the top-line data later this quarter.

RECONNECY 研究本質上試圖複製 CONNECT 研究中在完全甲基化患者身上觀察到的具有統計意義的療效訊號，並進行多項增強以進一步提高成功的可能性。我們已經完成了招生工作，並將於本季稍後公佈最終數據。

If positive, the RECONNECT study is expected to support regulatory approvals in both the US and EU, and Harmony holds global rights. ZYN002 has the potential to be the first and only approved treatment for any symptom domains in patients living with Fragile X.

如果結果呈陽性，RECONNECT 研究預計將獲得美國和歐盟監管部門的批准，而 Harmony 則擁有全球權利。ZYN002 有可能成為第一個也是唯一一個核准治療脆性 X 症候群患者任何症狀領域的藥物。

Moving on to the scientific rationale for ZYN002 in this condition. Fragile X syndrome is a rare genetic disorder caused by the mutation of FMR1 gene on the X chromosome, and it is the most common known inherited cause of intellectual impairment and autism spectrum disorders.

繼續討論此情況下 ZYN002 的科學原理。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，是已知導致智力障礙和自閉症譜系障礙最常見的遺傳原因。

Fragile X syndrome is characterized by FMR protein deficiency resulting in endocannabinoid dysfunction. ZYN002 interacts with the CD1 receptors, modulates the system, and restores the endocannabinoid homeostasis, thereby improving the neurobehavioral symptoms.

脆性 X 症候群的特徵是 FMR 蛋白缺乏，導致內源性大麻素功能障礙。ZYN002 與 CD1 受體相互作用，調節系統，恢復內源性大麻素穩態，進而改善神經行為症狀。

With ZYN002, we also remain on schedule to initiate a Phase 3 registrational trial in 22q deletion syndrome later this year, pending the results from the Fragile X program. This rare disorder with significant neurobehavioral symptoms similar to Fragile X has no approved therapies and also affects approximately 80,000 individuals each in the US and Europe.

對於 ZYN002，我們還將按計劃在今年稍後啟動 22q 缺失症候群的 3 期註冊試驗，等待脆性 X 症候群計畫的結果。這種罕見疾病具有與脆性 X 綜合徵相似的顯著神經行為症狀，目前尚無批准的治療方法，並且在美國和歐洲分別影響約 80,000 人。

Moving on to our sleep/wake franchise, we have made significant progress across our next generation pitolisant program. The pitolisant HD program, a higher dose pitolisant formulation with an optimized PK profile targeting enhanced efficacy for excessive data sleepiness and pursuing a differentiated label with an indication for fatigue and narcolepsy is on track for the Phase 3 initiation in Q4 2025.

繼續討論我們的睡眠/覺醒特許經營權，我們在下一代 pitolisant 計劃中取得了重大進展。Pitolisant HD 計畫是一種更高劑量的 Pitolisant 配方，具有優化的 PK 曲線，旨在增強對過度數據嗜睡的療效，並追求用於治療疲勞和發作性睡病的差異化標籤，預計將於 2025 年第四季度啟動第 3 階段。

Similarly, the Phase 3 study with pitolisant HD in patients with idiopathic hypersomnia, is also pursuing a differentiated level with an indication for [sleep] inertia and is also on track for initiation in Q4 2025. The target to-do for dates for both programs are in 2028.

同樣，針對特發性嗜睡症患者進行的 Pitolisant HD 第 3 期研究也在追求針對 [睡眠] 慣性的差異化水平，並且也有望於 2025 年第四季度啟動。這兩個項目的目標完成日期都是 2028 年。

Over to the pitolisant GR formulation, it is designed to address the potential for treatment-related GI side effects, especially since almost 90% of patients with narcolepsy experience GI symptoms. In addition, it also provides an ability to start at the therapeutic dose range, eliminating titration. This is a faster market strategy. We are demonstrating bio equivalent to WAKIX formulation. The top-line data from the pivotal BE study is expected in Q4 with a potential PDUFA in 2026.

至於 Pitolisant GR 配方，其設計目的是解決與治療相關的胃腸道副作用的可能性，特別是因為幾乎 90% 的嗜睡症患者都會出現胃腸道症狀。此外，它還提供了從治療劑量範圍開始的能力，無需滴定。這是一種更快的市場策略。我們正在展示與 WAKIX 配方等效的生物製劑。關鍵 BE 研究的頂線數據預計將於第四季度公佈，並可能在 2026 年獲得 PDUFA。

Utility patents have been filed for both pitolisant GR and pitolisant HD with potential exclusivity to 2044, securing long-term franchise value. Beyond pitolisant, our sleep/wake portfolio continues to advance with BP1.15205, a highly potent orexin-2 receptor agonist, demonstrating best-in-class potential in pre-clinical studies.

Pitolisant GR 和 Pitolisant HD 均已申請實用專利，其獨佔權可能持續至 2044 年，從而確保了長期特許經營價值。除了匹托利桑之外，我們的睡眠/覺醒產品組合還在不斷進步，其中包括強效食慾素-2受體激動劑BP1.15205，在臨床前研究中展現出一流的潛力。

At the recent sleep meeting, we presented a comprehensive preclinical safety and efficacy data that demonstrated efficacy at very low doses across all parameters of interest in a standard transgenic mouse model. The program remains on schedule for IMPD submission and first in human studies later this year, and we anticipate sharing clinical data in 2026.

在最近的睡眠會議上，我們展示了全面的臨床前安全性和有效性數據，證明了在標準基因轉殖小鼠模型中，所有感興趣的參數在極低劑量下均具有有效性。該計劃仍按計劃進行，將於今年稍後提交 IMPD 並首次進行人體研究，我們預計將於 2026 年分享臨床數據。

In our epilepsy franchise, we continue to actively enroll patients in two global Phase 3 registrational trials with EPX-100. The ARGUS study in Dravet syndrome, and the LIGHTHOUSE study in Lennox-Gastaut syndrome.

在我們的癲癇治療領域，我們繼續積極招募患者參加 EPX-100 的兩項全球 3 期註冊試驗。Dravet 症候群的 ARGUS 研究和 Lennox-Gastaut 症候群的 LIGHTHOUSE 研究。

In conclusion, our late-stage neurology portfolio is advancing with exceptional momentum, positioning us to potentially introduce multiple new products or indications every year over the next several years. Beyond the clinical and regulatory milestones, what truly drives us is the opportunity to transform care for hundreds of thousands of patients living with rare neurological disorders, many of whom currently have either no treatment options or therapies with sub-optimal efficacy and/or significant safety tolerability limitations.

總之，我們的後期神經病學產品組合正以非凡的勢頭發展，使我們能夠在未來幾年內每年推出多種新產品或適應症。除了臨床和監管里程碑之外，真正推動我們前進的是改變數十萬患有罕見神經系統疾病患者的護理的機會，其中許多患者目前要么沒有治療選擇，要么治療效果不佳和/或安全耐受性受到嚴重限制。

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 the clinical investigators and site personnel for all 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一切努力和承諾。

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 second quarter of 2025 earnings release and filed our 10-Q, where you'll find the details of our financial and operating results. We had a great first half of the year. We delivered another quarter of solid financial performance with continued double-digit top-line growth, sustained profitability, and robust cash generation.

謝謝你，庫馬爾，大家早安。今天上午，我們發布了 2025 年第二季財報並提交了 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。我們上半年過得非常愉快。我們又一個季度取得了穩健的財務業績，繼續保持兩位數的營收成長、持續的獲利能力和強勁的現金產生能力。

Our financial performance and profile positions us well to continue advancing our growth strategy for the remainder of the year and beyond. For the second quarter of 2025, we reported net revenues of $200.5 million compared to $172.8 million in the prior year quarter, representing a growth of 16%.

我們的財務表現和狀況使我們能夠在今年剩餘時間及以後繼續推進我們的成長策略。2025 年第二季度，我們的淨收入為 2.005 億美元，而去年同期為 1.728 億美元，成長了 16%。

Performance in the quarter reflects the strong underlying demand for WAKIX, offset by a reduction in trade inventories of a few days as we head into the summer months. Pre-reported total operating expenses for the second quarter of $114.2 million compared to $119.3 million for the same quarter in 2024.

本季的表現反映了對 WAKIX 的強勁潛在需求，但隨著進入夏季，貿易庫存減少了幾天，抵消了這一影響。第二季的預報告總營運費用為 1.142 億美元，而 2024 年同期為 1.193 億美元。

The expenses during the second quarter of 2025 include investments in advancing our late-stage pipeline and the commercialization of WAKIX in narcolepsy. We also recognize the $15 million IPRMD charge related to the CiRC research collaboration which Jeff mentioned. We have an option to acquire an exclusive license for each program. The agreement includes customary milestones and royalties based on continued development and potential commercialization.

2025 年第二季的費用包括對推進我們後期管道和 WAKIX 在嗜睡症治療中的商業化的投資。我們也承認 Jeff 提到的與 CiRC 研究合作相關的 1500 萬美元 IPRMD 費用。我們可以選擇為每個程式取得獨家許可。該協議包括基於持續開發和潛在商業化的慣例里程碑和特許權使用費。

We continue to show solid net income and margin. Non-GAAP adjusted net income for the second quarter of 2025 was $53.8 million or $0.92 per diluted share compared to $24.5 million or $0.43 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.

我們持續呈現穩健的淨收入和利潤率。2025 年第二季非公認會計準則調整後淨收入為 5,380 萬美元，即每股攤薄收益 0.92 美元，而去年同期為 2,450 萬美元，即每股攤薄收益 0.43 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。

Harmony ended the second quarter with $672 million in cash, cash equivalents, and investments on the balance sheet. The balance reflects strong cash generation from operations of approximately $79 million during the second quarter. Our cash position provides us the financial flexibility to execute on business development, as well as continued investments in our growing pipeline.

截至第二季末，Harmony 資產負債表上的現金、現金等價物和投資總額為 6.72 億美元。該餘額反映了第二季度營運產生的強勁現金流，約為 7,900 萬美元。我們的現金狀況為我們提供了執行業務發展的財務靈活性，以及對我們不斷增長的產品線的持續投資。

Looking ahead to the balance of 2025, our strong first-half results gives us increasing confidence in our full-year outlook. We are reiterating our revenue guidance of $820 million to $860 million, highlighting our progress towards a $1 billion-plus opportunity with WAKIX in narcolepsy alone. We expect continued quarter-over-quarter net revenue growth the balance of the year.

展望 2025 年，我們強勁的上半年業績讓我們對全年前景更加充滿信心。我們重申 8.2 億至 8.6 億美元的收入預期，強調我們僅在嗜睡症領域就與 WAKIX 合作實現 10 億美元以上的機會所取得的進展。我們預計今年餘下的季度淨收入將繼續保持環比成長。

With respect to expenses, we expect continued investment in R&D 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 milestones payments in 2025, including milestones for the completion of the Phase 3 trial for ZYN002 in Fragile X syndrome, $15 million on track for 2/3, along with a potential milestone of $10 million for positive top-line data from this trial.

關於費用，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，我們預計將繼續對研發進行投資。如前所述，我們預計 2025 年可能產生 2900 萬美元的研發里程碑付款，包括完成 ZYN002 治療脆性 X 綜合徵的 3 期試驗的里程碑付款、2/3 的按計劃付款 1500 萬美元，以及該試驗獲得積極頂線數據的潛在里程碑付款 1000 萬美元。

In addition, we expect a milestone of approximately $4 million in Q4 related to the initiation of Phase 1 trial in our orexin-2 program. In summary, we're having a very successful first half of the year and have confidence in the continued growth of WAKIX along with the advancement of our late-stage pipeline in the second half.

此外，我們預計第四季度將實現約 400 萬美元的里程碑收入，這與我們的 orexin-2 計畫啟動第一階段試驗有關。總而言之，我們今年上半年非常成功，並且對 WAKIX 的持續成長以及下半年後期管道的進步充滿信心。

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. My thanks to everyone for joining our call today and for your interest in Harmony Biosciences. At this juncture of our company's journey, I have never been more proud of the Harmony team or more excited about what lies ahead.

謝謝你，桑迪普。感謝大家今天參加我們的電話會議以及對 Harmony Biosciences 的關注。在我們公司發展歷程的這個關鍵時刻，我從未像現在這樣為 Harmony 團隊感到自豪，也從未像現在這樣對未來感到興奮。

The reasons for my excitement are many, but to highlight a few, WAKIX is on its way to a $1 billion-plus opportunity in narcolepsy alone. A robust, catalyst-rich, late-stage pipeline is poised to deliver one or more new product or indication launches every year over the next several years with peak sales potential of $3 billion to $6 billion in total.

我感到興奮的原因有很多，但其中最重要的一點是，WAKIX 僅在嗜睡症治療領域就有望獲得超過 10 億美元的商機。未來幾年內，強勁、富含催化劑的後期研發管線每年將推出一款或多款新產品或適應症，總峰值銷售潛力將達到 30 億至 60 億美元。

And we have a high degree of conviction and are very excited about our next major clinical catalyst coming later this quarter: the top-line data readout from our Phase 3 trial of ZYN002 in Fragile X syndrome. If positive, this could represent a transformational moment for both the Fragile X community and for Harmony Biosciences.

我們對此充滿信心，並對本季度晚些時候即將出現的下一個主要臨床催化劑感到非常興奮：ZYN002 治療脆性 X 綜合徵的 3 期試驗的頂線數據讀數。如果結果呈陽性，這可能代表著脆性 X 症候群社群和 Harmony Biosciences 的轉型時刻。

We have built something rare in our industry: a profitable, self-funding biotech company with an innovative late-stage pipeline poised to deliver meaningful value for both patients and shareholders alike. Because of this unique profile, we continue to execute from a position of strength. And that is what makes Harmony one of the most compelling growth stories in biotech today.

我們在業界創造了一些罕見的東西：一家盈利的、自籌資金的生物技術公司，擁有創新的後期產品線，準備為患者和股東帶來有意義的價值。由於這獨特的特性，我們能夠繼續以優勢地位執行任務。這也使得 Harmony 成為當今生技領域最引人注目的成長案例之一。

Thanks, everyone, and I will now turn the call back over to the operator for Q&A. Operator?

謝謝大家，現在我將把電話轉回接線生進行問答。操作員？

(Operator Instructions) Jay Olson, Oppenheimer.

（操作員指示）傑伊·奧爾森，奧本海默。

Congrats on all the progress. I wanted to focus on the RECONNECT top-line data readout, which I think you mentioned is still on track for this quarter. Could you please provide any additional color on the timing of when to expect that readout? It sounds like maybe it could be after Labor Day.

祝賀你取得的所有進展。我想重點關注 RECONNECT 的頂線數據讀數，我認為您提到的本季數據仍然正常。您能否提供有關預計讀數時間的更多詳細資訊？聽起來可能是勞動節之後。

And then just in terms of framing the expectations, can you just describe what would be clinically meaningful and what is your target for a successful outcome in this registrational Fragile X study. And finally, if you could just remind us the evidence that supports your confidence in ZYN002 achieving your target profile.

然後，就制定預期而言，您能否描述一下這項註冊脆性 X 症候群研究的臨床意義以及成功結果的目標是什麼。最後，如果您能提醒我們支持您對 ZYN002 實現目標的信心的證據。

Thank you for your questions and thanks for your coverage to Harmony. Welcome. Appreciate your initiation of coverage. I will -- Kumar can address your questions about the RECONNECT study and the opportunity in Fragile X syndrome.

感謝您的提問，也感謝您對 Harmony 的報導。歡迎。感謝您的報道。我會—庫馬爾可以回答您關於 RECONNECT 研究和脆性 X 綜合徵機會的問題。

Thank you, Jeff. Good morning, Jay. Thanks for the question. Yes, we are on track for top-line data in Q3, and we are very excited about this opportunity, not just because it's a major milestone for Harmony, but for patients with Fragile X syndrome and their caregivers in general.

謝謝你，傑夫。早安，傑伊。謝謝你的提問。是的，我們第三季的頂線數據進展順利，我們對這個機會感到非常興奮，這不僅是因為這是 Harmony 的一個重要里程碑，而且對於脆性 X 綜合徵患者及其護理人員來說也是如此。

Regarding the level of confidence, we have a high level of confidence and conviction in the Phase 3 CONNECT study because we are essentially trying to replicate the statistically significant findings that we saw in the last Phase 2/3 CONNECT study on the primary endpoint of social avoidance in patients with complete methylation.

關於信心水平，我們對第 3 階段 CONNECT 研究有很高的信心和信念，因為我們本質上是試圖複製我們在上一個第 2/3 階段 CONNECT 研究中看到的關於完全甲基化患者社交迴避的主要終點的統計顯著發現。

In terms of how we will define success, successful outcome will be defined by demonstrating a statistically significant outcome in the primary endpoint, which is social avoidance in patients with complete methylation, and the study is more than adequately powered to detect that difference.

關於我們如何定義成功，成功的結果將透過在主要終點展示統計學上顯著的結果來定義，即完全甲基化患者的社交迴避，並且該研究有足夠的能力檢測到這種差異。

Be positive, we have an opportunity here to bring the first and only approved treatment for any symptom domains in patients with Fragile X syndrome, and that's what we're really excited about.

保持樂觀，我們有機會為脆性 X 綜合徵患者帶來首個也是唯一一個獲批的針對任何症狀領域的治療方法，這才是我們真正感到興奮的事情。

Super helpful. Thanks for taking the question.

超有幫助。感謝您回答這個問題。

David Hoang, Deutsche Bank.

德意志銀行的 David Hoang。

Congrats on the progress and thanks for taking my questions. So first, I also want to ask on Fragile X. In terms of, I guess, the top-line readout, could you just outline for us the data that -- the types of data you expect to disclose in the topline, and at that time, would we have visibility on the result in the fully methylated versus partially methylated patients, and when might we know, I guess, how you plan to approach your filing strategy with the FDA if you would be pursuing fully methylated or all comers.

恭喜您的進展，感謝您回答我的問題。因此，首先，我也想問一下關於脆性 X 的問題。就頂線讀數而言，您能否為我們概述一下數據 - 您預計在頂線中披露的數據類型，以及屆時我們是否可以看到完全甲基化和部分甲基化患者的結果，以及如果您追求完全甲基化或所有方面，我們什麼時候可以知道您計劃如何向 FDA 制定備案策略。

And then just quickly on WAKIX as we are now in the back half of the year, I was wondering if you could just talk a little bit about the pushes and pulls that get you to the upper versus the lower end of the guidance range.

然後，關於 WAKIX 的簡短討論，由於我們現在已經進入下半年，我想知道您是否可以稍微談談推動和拉動您達到指導範圍的上限和下限的因素。

I'll ask Kumar to comment further on the strategy for Fragile X and the ZYN readout, and Adam can address the question about WAKIX. Kumar?

我會請 Kumar 進一步評論 Fragile X 和 ZYN 讀數的策略，Adam 可以回答 WAKIX 的問題。庫馬爾？

Thanks for the question. So in terms of what we disclose at the top-line data for Fragile X syndrome, it will be a standard top-line data readout, which is the demographic data, safety, and tolerability data, the efficacy on the primary endpoint, and the key secondary [end].

謝謝你的提問。因此，就我們在脆性 X 綜合徵的頂線數據中披露的內容而言，它將是一個標準的頂線數據讀數，即人口統計數據、安全性和耐受性數據、主要終點的療效以及關鍵的次要[結尾]。

In terms of how we will proceed next, look, if the study shows statistical significant outcome on the primary endpoint, we will move rapidly to have a pre-NDA meeting and submit an NDA. In an indication like Fragile X syndrome where there are no approved treatments, I think it's fair to expect a priority reveal, and if everything goes according to plan, hopefully we will have an approved product by the end of next year.

關於我們下一步將如何進行，如果研究在主要終點顯示出統計上顯著的結果，我們將迅速召開 NDA 前會議並提交 NDA。對於脆性 X 症候群這種尚無核准治療方法的疾病，我認為期待優先揭露是合理的，如果一切按計劃進行，希望我們能在明年年底前獲得核准的產品。

Thanks, Kumar. Adam?

謝謝，庫馬爾。亞當？

Yeah, thanks for the question on WAKIX. We're really pleased with the performance that we're seeing on WAKIX at this stage. We're now in our 6th year on the market. We achieved $200.5 million in net revenue for the second quarter. That's a 16% year-over-year increase in year six, which is fantastic. We also achieved 7,600 average patients in the quarter. That's an increase of 400 average patients in Q2, and that is among the highest increases we have seen in any quarter since launch.

是的，感謝您在 WAKIX 上提出的問題。我們對 WAKIX 目前的表現感到非常滿意。我們進入市場已經六年了。我們第二季度實現了2.005億美元的淨收入。這是第六年同比增長 16%，這真是太棒了。本季我們也接待了平均 7,600 名患者。這意味著第二季度平均患者人數增加了 400 人，這是我們自推出以來在各個季度中看到的最高增幅之一。

So the performance, steady drumbeat continues. In terms of puts and takes, I would say that WAKIX is a highly differentiated products, first and only non-scheduled treatment option for patients who were supported by broad payer coverage, with 80% of lives covered, and that's been the case for years. We don't expect any changes in payer coverage.

因此表演中，穩定的鼓聲仍在繼續。就利弊而言，我想說 WAKIX 是一種高度差異化的產品，是第一個也是唯一一個為獲得廣泛付款人覆蓋的患者提供的非計劃治療選擇，覆蓋了 80% 的患者的生命，多年來一直如此。我們預計付款人覆蓋範圍不會有任何變化。

We have a very experienced team. Many of our team members actually started at the launch of WAKIX, and we have a unique commercial model that provides really high levels of service to HCPs, office staff, as well as patients.

我們擁有一支經驗豐富的團隊。實際上，我們的許多團隊成員都是在 WAKIX 推出時就開始工作的，我們擁有獨特的商業模式，可以為 HCP、辦公室工作人員以及患者提供真正高水準的服務。

And I would highlight that in terms of HCP prescribers, we continue to see increased preference share in the 4,000 oxybate REMS enrolled clinicians, and we see increased preference share and the addition of new prescribers in the 5,000 non-oxybate REMS enrolled HCP group as well. So those are probably the key drivers of that continued performance.

我想強調的是，就 HCP 處方者而言，我們繼續看到 4,000 名參加過羥基丁酸鹽 REMS 的臨床醫生的偏好份額有所增加，並且我們也看到 5,000 名參加過非羥基丁酸鹽 REMS 的 HCP 組中的偏好份額有所增加並且有新的處方者加入。因此，這些可能是持續表現的關鍵驅動因素。

Sandip, I don't know if you want to add anything?

Sandip，我不知道您是否想補充什麼？

No, I think -- as you said, really a strong start to the year and really gives us increased confidence certainly in our guidance range. Look, we're very comfortable with where things are right now, it was -- it's really -- at the end of the day, it's the underlying demand that really drives overall net sales and as in terms of the pushes and pulls, it's the typical factors that will typically impact where we end up in the range, everything from obviously this continued net patient ads certainly have an impact, any potential growth and net impact, as well as trade inventory impacts as well.

不，我認為——正如你所說，今年的開局確實很強勁，這確實讓我們對我們的指導範圍更有信心。你看，我們對現在的情況非常滿意，這真的是——說到底，是潛在需求真正推動了整體淨銷售額，至於推動和拉動，是典型因素通常會影響我們最終的範圍，顯然，從持續的淨患者廣告到任何潛在的增長和淨影響，以及貿易庫存影響，一切都肯定會產生影響。

As you know, we have a fairly -- we have a concentrated customer base overall, so just order patterns overall. However -- but we're very confident in the guiding range, consensus currently falls right within the range, and we're -- that seems very reasonable place.

如您所知，我們擁有相當集中的客戶群，因此總體而言，我們的訂購模式是一致的。但是——我們對指導範圍非常有信心，目前的共識正好在這個範圍內，而且我們——這似乎是非常合理的地方。

Ash Verma, UBS.

瑞銀的 Ash Verma。

Thanks for taking the question. So I just wanted to ask on Fragile X, I want to understand the implications of full methylation. So does choosing full methylation versus partial means a haircut to the patient population, just if you can give us a sense of like what is the full methylation Fragile X patients in the US versus the 80,000 that you mentioned.

感謝您回答這個問題。所以我只是想問脆性 X，我想了解完全甲基化的含義。因此，選擇完全甲基化還是部分甲基化是否意味著對患者群體的削減，如果您能讓我們了解美國的完全甲基化脆性 X 患者與您提到的 80,000 名患者的情況。

And then secondly, can you talk about some -- any kind of like regulatory or clinical trial conduct analogs here? So has FDA accepted applications for these type of rare pediatric conditions with the data showing efficacy only in a fully turned off gene.

其次，您能談談一些類似的監管或臨床試驗行為嗎？因此，FDA 已經接受了針對此類罕見兒科疾病的申請，數據顯示該藥物僅在基因完全關閉的情況下才有效。

Thank you for the question. So in terms of the split between complete methylation versus partial methylation, approximately 60% to 70% of patients with Fragile X syndrome have complete methylation, and the rest have partial methylation. So in terms of us choosing the complete methylation as the target population, this was a data-driven approach based on the findings that we saw in the CONNECT study. And this fits into the etiology, the pathophysiology of Fragile X syndrome that we know about.

謝謝你的提問。因此，就完全甲基化與部分甲基化之間的區分而言，大約 60% 至 70% 的脆性 X 綜合徵患者俱有完全甲基化，其餘患者俱有部分甲基化。因此，就我們選擇完全甲基化作為目標族群而言，這是一種基於我們在 CONNECT 研究中看到的發現的數據驅動方法。這符合我們所知的脆性 X 症候群的病因和病理生理學。

Basically what happens in patients with complete methylation is they have more than 200 trinucleotide repeats of CGG, which results in almost complete silencing of the gene, which means that they are hardly able to produce any FMR protein which causes significant dysfunction of the endocannabinoid system.

基本上，完全甲基化的患者體內的 CGG 三核苷酸重複超過 200 個，導致基因幾乎完全沉默，這意味著他們幾乎無法產生任何 FMR 蛋白，導致內源性大麻素系統嚴重功能障礙。

And the ZYN002 interacts with CB1 receptors, reset the endocannabinoid system, so these patients have a higher burden of symptoms, the mechanism of action fits nicely well in treating the symptoms in these patients.

ZYN002 與 CB1 受體相互作用，重置內源性大麻素系統，因此這些患者的症狀負擔更重，其作用機制非常適合治療這些患者的症狀。

In terms of the FDA, yes, we actually have had extensive discussions with the FDA and we have full alignment with the FDA on the study design, the target patient population, the primary endpoint. In fact, the study is designed not just to meet the requirements of FDA, but EMA as well. So should the study be positive, we will be pursuing an indication both in the US and in Europe.

就 FDA 而言，是的，我們實際上已經與 FDA 進行了廣泛的討論，並且在研究設計、目標患者群體和主要終點方面與 FDA 完全一致。事實上，這項研究的設計不僅是為了滿足 FDA 的要求，也是為了滿足 EMA 的要求。因此，如果研究結果是正面的，我們將在美國和歐洲尋求治療。

Yeah, Ash, I would just add that I think you know this strategy sort of follows the science as well as the data. And the Phase 3 RECONNECT trial is designed to replicate the positive findings in the Phase 2/3 CONNECT study in patients with complete methylation. And then in addition, obviously with no approved therapies, with regard to -- where the bar would be set, with a high unmet need in this patient population.

是的，Ash，我只想補充一點，我認為你知道這種策略既遵循科學，也遵循數據。階段 3 RECONNECT 試驗旨在複製第 2/3 階段 CONNECT 研究在完全甲基化患者中的積極發現。此外，顯然目前還沒有批准的療法，就標準而言，該患者群體存在很高的未滿足需求。

Thank you.

謝謝。

Graig Suvannavejh, Mizuho.

瑞穗的 Graig Suvannavejh。

Thanks for taking my question. I was curious about your new CiRC collaboration. I was just wondering, can you walk us through the thoughts, especially from a B&D and corporate strategy perspective, the self-therapy approach is interesting for sure, but I don't think it's been a proven area, and so I just wanted to get your thoughts just on the collaboration, but also maybe future BD direction.

感謝您回答我的問題。我對您與 CiRC 的新合作感到好奇。我只是想知道，您能否向我們介紹一下您的想法，特別是從 B&D 和企業策略的角度來看，自我治療方法當然很有趣，但我認為這不是一個已被證實的領域，所以我只是想听聽您對合作的看法，也許還有您對未來 BD 方向的看法。

Certainly. Thanks for your question. Yeah, I think in terms of the CiRC collaboration, we see it as an exciting opportunity, obviously a very early sort of discovery phase opportunity, but one that reflects our overall commitment to patients with serious rare neurologic disorders in an advanced stage. It's strategically aligned with our pipeline and potential cellular therapies for refractory epilepsy in one of the discovery programs and the other treatment resistant narcolepsy based on sort of reprogramming the cellular platform.

當然。謝謝你的提問。是的，我認為就 CiRC 合作而言，我們認為這是一個令人興奮的機會，顯然是一個非常早期的發現階段的機會，但它反映了我們對晚期嚴重罕見神經系統疾病患者的整體承諾。它與我們的管道和潛在的難治性癲癇細胞療法在策略上保持一致，其中一個發現項目是基於對細胞平台進行重新編程，另一個發現項目是基於對難治性發作性睡病進行治療。

So again, while it's still early, we see this is potentially the resulting in kind of the next generation of innovative disease modifying therapies for patients with advanced neurologic disorders. With that, Kumar can comment a little further on the platform and what we saw in the opportunity.

因此，雖然現在還為時過早，但我們認為這可能會為晚期神經系統疾病的患者帶來下一代創新的疾病改良療法。有了這一點，庫馬爾可以進一步評論該平台以及我們所看到的機會。

Thanks for the question. Look, with the CiRC, what really attracted and really fascinated us with the novel cellular reprogramming platform that CiRC utilizes that offers significant competitive and manufacturing advantages compared to embryonic or induced pluripotent stem cells. It overcomes many challenges, like, say for example, the consistency and the reliability of readily sourced GMP grade cell lines because these are fibroblast-derived cells that are induced to transform into [progenerators] of interest based on a small molecule epigenetic modifier and growth factor.

謝謝你的提問。看看 CiRC，真正吸引我們、讓我們著迷的是 CiRC 所採用的新型細胞重編程平台，與胚胎或誘導多能幹細胞相比，該平台具有顯著的競爭和製造優勢。它克服了許多挑戰，比如說，容易獲得的 GMP 級細胞系的一致性和可靠性，因為這些細胞是成纖維細胞衍生的細胞，它們基於小分子表觀遺傳修飾劑和生長因子被誘導轉化為感興趣的[祖細胞]。

And also, this particular platform could potentially enable allogenic cryopreserved (inaudible) to use therapies that require no manipulation at the point of care. And obviously, because we are not using the stem cells, there is less risk of the (inaudible) and manufacturing inefficiencies that are seen with stem cells. So we are very excited about the collaboration both in epilepsy and in narcolepsy and look forward to this data generation from CiRC and we'll provide more information as we make progress.

此外，這個特殊的平台可能使同種異體冷凍保存（聽不清楚）能夠使用在護理點不需要操作的療法。顯然，因為我們不使用幹細胞，所以出現幹細胞所出現的（聽不清楚）和製造效率低下的風險較小。因此，我們對癲癇和嗜睡症領域的合作感到非常興奮，並期待 CiRC 產生這些數據，我們將在取得進展時提供更多資訊。

Yeah. And Graig I would add, I think that we see this as a kind of an opportunistic play, if you will. Again, very early discovery phase strategically aligned. With regards to our other BD efforts as you asked, obviously, our strategy is to continue to grow and build out our pipeline and with a very strong balance sheet, we see in terms that we're always looking for opportunities to deploy our cash and drive value for shareholders.

是的。我想補充一點，格雷格，如果你願意的話，我認為我們認為這是一種機會主義的玩法。再次強調，早期的發現階段是策略一致的。至於您所問的我們的其他 BD 工作，顯然，我們的策略是繼續發展和擴大我們的產品線，憑藉非常強勁的資產負債表，我們看到我們一直在尋找機會部署我們的現金並為股東創造價值。

We continue to actively evaluate different opportunities across the spectrum development phase from early to late potentially on market opportunities. Obviously, we're in a good position to execute on our growth strategy. As always, we take a disciplined approach: thoughtful, strategic to -- how we build out the pipeline thus far, and some of the opportunities we see ahead. We feel that we're just getting started with regards to some of the opportunities ahead of us.

我們將繼續積極評估從早期到晚期的整個開發階段的不同機會，以尋找潛在的市場機會。顯然，我們已做好充分準備來執行我們的成長策略。像往常一樣，我們採取嚴謹的方法：深思熟慮、策略性地考慮我們迄今為止如何建立管道，以及我們看到的一些未來機會。我們覺得，就我們面前的一些機會而言，我們才剛開始。

Sandip, any further comments on the capacity?

桑迪普，對於容量還有其他評論嗎？

Yeah, look, I mean, this quarter was a really strong quarter in terms of cash generation. We generated from operation $79 million closing the quarter with over $670 million in cash, so I think we're in a highly strong position to be able to transact. I mean, look, we continue to look for opportunities as you mentioned Jeff, across the spectrum overall.

是的，我的意思是，就現金產生而言，這個季度確實是一個強勁的季度。本季末我們的營運收入為 7,900 萬美元，現金超過 6.7 億美元，因此我認為我們處於非常有利的交易地位。我的意思是，你看，正如你提到的傑夫，我們會繼續在各個方面尋找機會。

We'll continue to be disciplined in terms of how we deploy our capital, but our filters continue to be the same, so I think we're -- it's hard to predict timing at the end of the day on these types of things, but I think we're really continuing to be in a strong position. We have a very unique profile as a company, highly profitable, generating positive cash flow and the ability to deploy it in the market that is an attractive market at this point, so --

我們將繼續嚴格控制資本配置，但我們的篩選條件保持不變，因此我認為，我們——很難預測這類事情最終的時機，但我認為我們確實將繼續處於強勢地位。我們公司的特點非常獨特，利潤豐厚，產生正現金流，並且有能力在目前頗具吸引力的市場中部署它，因此--

Thanks, Sandip.

謝謝，桑迪普。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

I have some questions on the orexin, and sorry if I missed this, but with the data that you're anticipating next year, is that in healthy sleep-deprived volunteers or is that going to be an actual narcolepsy patients, so just help us understand what to expect for next year and to the extent you're not yet testing narcolepsy in IH patients, when do you expect to do so? That's number one.

我對食慾素有一些疑問，如果我錯過了這一點，很抱歉，但是根據您預計明年的數據，這些數據是針對健康的睡眠不足的志願者，還是針對真正的嗜睡症患者，所以請幫助我們了解明年的預期情況，並且就您尚未在 IH 患者中測試嗜睡症而言，您預計何時進行測試？這是第一點。

And then number two, in terms of differentiation, I know you've talked about it as potentially being best in class, but we've got a number of more advanced orexins that have shown MWT improvements well north of 20 minutes and we've seen real validation here. So what do you need to see in order to legitimately make that claim that your orexin is indeed best in class?

第二，就差異化而言，我知道您已經談到它可能是同類產品中最好的，但我們有許多更先進的食慾素，它們的 MWT 改善已經遠遠超過 20 分鐘，我們在這裡看到了真正的驗證。那麼，您需要看到什麼才能合法地宣稱您的食慾素確實是同類產品中最好的呢？

Thanks for your question. Kumar, our position on the orexin programs?

謝謝你的提問。 Kumar，我們對食慾素計畫的立場是什麼？

Yeah, thank you, Jeff. Good morning, David. Thank you for the question. Regarding our orexin program, if they -- actually, you did not miss anything because we have not talked about how we are going to approach the first in human studies.

是的，謝謝你，傑夫。早安，大衛。謝謝你的提問。關於我們的食慾素計劃，如果他們——實際上，你沒有錯過任何東西，因為我們還沒有討論我們將如何進行人體研究的第一次。

We are on track for IMPD submission and comment first in human studies later this year. The way we are approaching this is start with the single ascending dose study in healthy volunteers and in parallel, also conduct healthy volunteer sleep deprivation study because as you know, BP1.15205 is the most potent orexin receptor agonist that is out there based on the data that is disclosed in the public domain, and we do want to get a better idea in terms of the dose range before we progress this into patients.

我們將在今年稍後首先在人體研究中提交 IMPD 並進行評論。我們採取的方式是，首先在健康志願者中進行單次遞增劑量研究，同時進行健康志願者睡眠剝奪研究，因為如您所知，根據公開的數據，BP1.15205 是目前最有效的食慾素受體激動劑，我們確實希望在將其用於患者之前，對劑量範圍有更好的了解。

What you can expect next year is data from healthy volunteers from single (inaudible) dose study, and the healthy volunteers sleep deprivation study as well. How we are going to proceed after that is something that we are still thinking through, depending on what our -- what we are learning from others as well in this field.

明年您可以期待的是來自單一劑量（聽不清楚）研究的健康志願者的數據，以及健康志願者睡眠剝奪研究的數據。我們仍在思考接下來該如何進行，這取決於我們——以及我們在這個領域從其他人身上學到了什麼。

In terms of how do we differentiate, David, I think it's too early to comment based on the preclinical data which we presented at the sleep meeting, we showed that potency is important and potency translated to efficacy at very low doses. In fact, at 0.03 mg per kg in narcolepsy model, we showed statistically significant difference in wakefulness time, the lowest dose that they ever studied in this particular model.

關於我們如何區分，大衛，我認為現在根據我們在睡眠會議上提供的臨床前數據發表評論還為時過早，我們表明效力很重要，並且效力在非常低的劑量下轉化為功效。事實上，在嗜睡症模型中，以每公斤 0.03 毫克的劑量，我們顯示出清醒時間的統計學上顯著差異，這是他們在該特定模型中研究過的最低劑量。

We anticipate the high potency, and therefore low dose gives us the flexibility -- the dosing flexibility to target all three central disorders of hypersomnia and not just NT1 but also NT2 and idiopathic hypersomnia without having the safety or tolerability concerns. So this is our strategy right now.

我們預期其具有高效力，因此低劑量為我們提供了靈活性——劑量靈活性可以針對嗜睡症的所有三種中樞障礙，不僅是 NT1，還有 NT2 和特發性嗜睡症，而無需擔心安全性或耐受性。這就是我們現在的策略。

Thank you.

謝謝。

Danielle Brill, Truist.

丹妮爾·布里爾，Truist。

Thanks so much for the questions. As a follow up to the prior question, I wanted to ask in general, what -- how we should think about the potential impact of (inaudible) orexin-2 entering the market, and how confident you are that the WAKIX expanse can continue to grow with orexin-2s in the market.

非常感謝您的提問。作為對上一個問題的跟進，我想問一下，我們應該如何看待（聽不清楚） orexin-2 進入市場的潛在影響，以及您對 WAKIX 擴張能夠隨著 orexin-2 進入市場而繼續增長有多大信心。

And then just on the quarter I wanted to clarify, it looks like the quarter-over-quarter growth was lower than what you typically observed in the past, despite the high number of new patient ads in the quarter. Was this just an inventory drawdown, or can you speak to the dynamics that were at play here, such as gross to net compliance and any other factors?

然後我想澄清一下，就本季而言，儘管本季度新患者廣告數量較多，但環比增長似乎低於過去通常觀察到的水平。這只是庫存減少嗎？或者您能否談談這裡起作用的動態因素，例如總合規性與淨合規性以及任何其他因素？

Thanks for your questions. In terms of the impact of orexins, how we see -- as we follow these programs closely, I'll ask Adam in regards to -- we still continue to see this market as a polypharmacy market, with multiple mechanisms and how you're seeing that from a commercial perspective going forward.

感謝您的提問。就食慾素的影響而言，我們如何看待——當我們密切關注這些項目時，我會問亞當——我們仍然將這個市場視為具有多種機制的多藥市場，以及您如何從商業角度看待這一點。

Yeah, thanks, Jeff, and thank you for the question. We're excited about orexins as a potential new treatment option for patients and as Kumar mentioned, we're very confident in the molecule that we have in our pipeline. There's still some questions to be addressed as a class, I think, dosing, label, long-term safety and tolerability, not to mention pricing and access.

是的，謝謝傑夫，謝謝你的提問。我們很高興看到食慾素有望成為患者的一種新治療選擇，正如庫馬爾所提到的，我們對我們研發的分子非常有信心。我認為，作為一個類別，仍有一些問題需要解決，劑量、標籤、長期安全性和耐受性，更不用說定價和獲取途徑了。

Now with WAKIX, this is the only non-scheduled treatment option. It's been on the market for now more than six years, really steady performance quarter over quarter over that period, and that's despite new brand and generic entrances coming in. I think that's because physicians see WAKIX is highly differentiated. They perceive it to be well tolerated and has broad clinical utility, and we expect that to continue.

現在有了 WAKIX，這是唯一的非計劃治療選擇。它已經上市六年多了，儘管有新的品牌和通用產品進入市場，但在此期間，其季度表現仍然非常穩定。我認為這是因為醫生認為 WAKIX 具有高度的差異性。他們認為它耐受性良好且具有廣泛的臨床應用，我們預計這種情況將持續下去。

At the time of orexin's launch, HCPs will have more than eight years of clinical experience. It's a very familiar therapeutic option. And with the -- Jeff mentioned with the polypharmacy approach to treatment, we expect WAKIX will continue to be added to therapy for patients, broadly. Not to mention that there's evidence to suggest that orexin and histamine actually have a synergistic effect. So we're very confident in the continued growth and performance of WAKIX.

在 Orexin 上市時，HCP 將擁有八年以上的臨床經驗。這是一個非常熟悉的治療選擇。而且，Jeff 提到了多重藥物聯合治療方法，我們預期 WAKIX 將繼續廣泛地應用於患者的治療中。更不用說有證據表明食慾素和組織胺實際上具有協同作用。因此，我們對 WAKIX 的持續成長和業績非常有信心。

Thanks. With regards to the (inaudible) performances, Sandip, if you can comment on that?

謝謝。關於（聽不清楚）表演，桑迪普，您能對此發表評論嗎？

Sure, happy to comment on that. I think -- as I mentioned, generally, look, our results so far, gives us increased confidence in the revenue guide of $820 million to $860 million. Fundamentals are very strong. We had strong growth even in the quarter of 16% versus prior year. And in fact -- I mean, in Q2, getting to your point, it's really underlying performance is probably even stronger than I would say the net revenues would indicate.

當然，我很高興對此發表評論。我認為——正如我所提到的，總的來說，我們迄今為止的業績讓我們對 8.2 億至 8.6 億美元的收入預期更有信心。基本面非常強勁。與去年同期相比，本季我們的成長率仍然強勁，達到 16%。事實上——我的意思是，在第二季度，回到你的觀點，它的實際潛在表現可能比我所說的淨收入所顯示的還要強勁。

And as I mentioned in my Q1 call, we did anticipate and we did see a trade inventory drawdown of approximately a few days as we head into the summer month. Typically, what happens with trade inventory is, Q4, Q1 tends to be a little bit higher; Q2, Q3 tends to be a bit lower, generally, but it's -- I think the more important point is really looking at the fundamentals of our business and the forward demand of one of the strongest quarters we've had in terms of net patient ads.

正如我在第一季電話會議上提到的那樣，我們確實預料到，而且隨著夏季的到來，我們確實看到貿易庫存將減少大約幾天。通常情況下，貿易庫存的情況是，第四季度、第一季度往往會高一點；第二季度、第三季度往往會低一點，但我認為更重要的一點是真正關注我們業務的基本面，以及就淨患者廣告而言，我們經歷過的最強勁的季度之一的未來需求。

And generally, again, it gives us really strong confidence in the balance of the year and you know we expect very strong quarter-over-quarter growth for the next two quarters to finish out the year.

總體而言，這再次讓我們對今年的收支平衡充滿信心，我們預計今年接下來兩個季度的環比成長將非常強勁。

Yeah, so I think just to reiterate, I think underlying business fundamentals remain strong. I think some variability in inventory from quarter to quarter, as Sandip alluded to. Obviously, it's the base of patients, increases. And then also, with only three specialty pharmacies in terms of the ordering patterns, so I think a couple days of inventory, with regards to that fluctuation. But overall, we are confident in reaffirming guidance for the year. We're comfortable with the street's kind of estimates of where we are. This business continues to grow and excited as our pipeline advances and the opportunities ahead.

是的，所以我想重申一下，我認為潛在的商業基本面仍然強勁。正如桑迪普所提到的，我認為庫存每季都會有所不同。顯然，患者基數正在增加。而且，就訂購模式而言，只有三家專業藥局，所以我認為庫存量只有幾天，波動較大。但總體而言，我們有信心重申今年的指導。我們對街道對我們所在位置的估計感到滿意。隨著我們的管道不斷進步以及未來機會的不斷湧現，這項業務將繼續成長並令人興奮。

Very helpful. Thank you so much.

非常有幫助。太感謝了。

[Karin Johnson], Goldman Sachs.

[卡琳·約翰遜]，高盛。

Good morning. This is Eric on for Karin Johnson. So I just wanted to ask a question elaborating on the last little bit, specifically, how should we think about net price for WAKIX this quarter and specifically moving towards the back half of 2025 and beyond, and to what extent are you using price as a lever to improve volume or drive broader adoption?

早安.我是艾瑞克，為卡琳·約翰遜報道。因此，我只想問一個問題來詳細說明最後一點，具體來說，我們應該如何看待本季度 WAKIX 的淨價，特別是到 2025 年下半年及以後，以及您在多大程度上利用價格作為槓桿來提高銷量或推動更廣泛的採用？

Thanks for your question. Sandip?

謝謝你的提問。桑迪普？

Yeah, I think in terms of net price evolution, it would be very similar to what we've seen in past years. Typically, the first quarter is the lowest just as we have higher growth and net deductions. Typically, that happens with the insurance plans reset and typically improves in the balance of the year. So we did see some improvement as we went into Q2, but obviously, as we as we go into the further quarters, we'll continue to see improvement that will help to realize a good portion of the price increase that we took earlier this year.

是的，我認為就淨價格演變而言，它與我們過去幾年看到的情況非常相似。通常，第一季是最低的，因為我們的成長和淨扣除額較高。通常，這種情況會在保險計劃重置時發生，並且通常會在一年的餘額中得到改善。因此，進入第二季度時我們確實看到了一些改善，但顯然，隨著進入下幾個季度，我們將繼續看到改善，這將有助於實現我們今年早些時候所採取的大部分價格上漲。

Thanks, Sandip.

謝謝，桑迪普。

Pete Stavropoulos, Cantor Fitzgerald.

皮特·斯塔夫羅普洛斯，康托·菲茨傑拉德。

Thank you for taking my questions and congrats on the quarter. I got two questions. The primary endpoint for RECONNECT, the social avoidance, a domain for the ABC checklist for (inaudible), it's an observer scale, either parents' or caregivers' score. Can you just talk about this outcome, potential variability, the expected placebo response, and what measures you've taken to mitigate the placebo response and are there any other major differences between CONNECT and RECONNECT?

感謝您回答我的問題，並祝賀本季取得的成績。我有兩個問題。RECONNECT 的主要終點是社交迴避，這是 ABC 清單的一個領域（聽不清楚），它是一個觀察者量表，可以是父母或照顧者的分數。您能否談談這個結果、潛在的變異性、預期的安慰劑反應以及您採取了哪些措施來減輕安慰劑反應，CONNECT 和 RECONNECT 之間還有其他主要區別嗎？

And the second question for Adam, you joined Harmony over 1.5 quarters ago. I'm curious to hear your views on what levers you may be able to pull to accelerate growth and build offwhat is already a successful franchise, and also plans for life cycle management.

第二個問題是問亞當，你一個半季前加入了 Harmony。我很想聽聽您的看法，您可以採取哪些措施來加速成長並鞏固已經成功的特許經營權，以及生命週期管理計劃。

Yeah, Pete, thanks for your questions. Thanks for picking coverage on Harmony. Appreciate that. Kumar?

是的，皮特，謝謝你的提問。感謝您選擇 Harmony 的報導。非常感謝。庫馬爾？

Good morning, Pete. Thanks for the question. Regarding the social avoidance subscale within the broader aberrant behavior checklist, you're absolutely right. This is an observable scale. As you know, ABC has been used extensively, a very well validated scale. We have a lot of experience with this particular scale. In terms of variability and placebo, great question. Look, in any neuropsych trial, these are something that we carefully watch for.

早安，皮特。謝謝你的提問。關於更廣泛的異常行為清單中的社交迴避分量表，您完全正確。這是一個可觀察的尺度。眾所周知，ABC 已被廣泛使用，是一種經過充分驗證的量表。我們對這種特殊的規模有豐富的經驗。就變異性和安慰劑而言，這是一個很好的問題。你看，在任何神經心理學試驗中，這些都是我們要仔細觀察的。

In this particular study, we have multiple checks and balances to manage it, including rigorous inclusion exclusion criteria. These are the patients biologically identified based on full mutation, complete methylation, with a significant level of symptoms.

在這項特定的研究中，我們有多重製衡措施來管理它，包括嚴格的納入排除標準。這些是根據完全突變、完全甲基化進行生物學識別的患者，具有明顯的症狀。

We know the standard deviation for this particular instrument, not just in general, but in patients with Fragile X syndrome, and we are obviously monitoring [blinded] data that we have and thus far where we are, we feel good about it.

我們知道這種特定儀器的標準差，不僅是一般情況，而且是脆性 X 綜合徵患者的標準差，而且我們顯然正在監測我們擁有的[盲法]數據，到目前為止，我們對此感覺良好。

In terms of differences between CONNECT and RECONNECT study, the primary endpoint (inaudible) is still the same, which is social avoidance upscale within the broader ABC scale. The target population is patients with complete methylation only and we made some other enhancements like for example, we increased the duration of treatment by four weeks. We increased the dose in patients who weigh more than 50 kilograms.

就 CONNECT 和 RECONNECT 研究之間的差異而言，主要終點（聽不清楚）仍然相同，即更廣泛的 ABC 量表中的社交迴避高檔化。目標族群是僅有完全甲基化的患者，我們做了一些其他改進，例如，我們將治療時間延長了四週。我們增加了體重超過50公斤的患者的劑量。

This was done based on the learning from the CONNECT study to enhance the probability (inaudible). As I mentioned earlier, a high level of confidence and conviction in this program, and really the opportunity that's in front of us, if the study is positive, we have an opportunity to bring the first and only treatment for patients with Fragile X syndrome.

這是根據 CONNECT 研究的經驗進行的，旨在提高（聽不清楚）。正如我之前提到的，我們對這個計畫充滿信心和信念，而且我們面前還有真正的機會，如果研究結果是正面的，我們就有機會為脆性 X 症候群患者帶來第一種也是唯一一種治療方法。

Thanks, Kumar. Adam, your thoughts on levers for growth in the WAKIX business.

謝謝，庫馬爾。亞當，您對 WAKIX 業務成長槓桿有何看法？

Thanks for the question, Pete, and actually levers of opportunity is a term that we talk about quite frequently in Harmony. It's a big focus. And I have to give credit to the team, the team here really does have a history of growth mindset looking for continued improvement opportunities. What we've been discussing is how can we continue to improve our top-line demand growth. So average referrals per day, and then conversion of those referrals into dispensing events.

謝謝你的提問，Pete，實際上機會槓桿是我們在 Harmony 中經常談論的術語。這是一個很大的焦點。我必須讚揚這個團隊，這裡的團隊確實有著成長心態，尋求持續改善的機會。我們一直在討論的是如何繼續提高我們的營收需求成長。因此，每天的平均建議次數，然後將這些推薦轉換為分配事件。

So how can we make sure that our process is efficient and effective for patients to secure a dispense and then retention over time? How can we provide the service that supports HCPs, the office staff, and the patient, and to ensure that they maintain or remain on therapy over time. So we've identified levers that we're going after. The work has started and I'm confident that the work of the team is going to continue to help drive that performance.

那麼，我們如何確保我們的流程高效且有效，以便患者能夠獲得配藥並長期保留藥物？我們如何提供支持 HCP、辦公室工作人員和患者的服務，並確保他們長期維持或繼續接受治療。因此，我們已經確定了我們要追求的槓桿。工作已經開始，我相信團隊的工作將繼續幫助推動這項績效。

Thanks, Adam.

謝謝，亞當。

Thank you very much for taking my questions and I'm glad to (inaudible).

非常感謝您回答我的問題，我很高興（聽不清楚）。

Patrick Trucchio, HC Wainwright.

派崔克·特魯基奧、HC·溫賴特。

Just a couple of follow-up questions from us in the pipeline. The first is on pitolisant HD. I'm just wondering what the expectation to initiate Phase 3 trials in the fourth quarter. Can you talk to potential trial design or differentiation goals with this program? And then separately regarding Fragile X, assuming a positive RECONNECT readout, how are you thinking about the commercial bill for ZYN002.

我們還有幾個後續問題。第一個是在 pitolisant HD 上。我只是想知道在第四季度啟動第三階段試驗的預期是什麼。您能談談該計劃的潛在試驗設計或差異化目標嗎？然後單獨討論脆性 X，假設 RECONNECT 讀數為正，您如何看待 ZYN002 的商業帳單。

Specifically, I'm wondering if you can discuss more about the engagement with KOL's advocacy groups and payers, and what does this suggest about market receptivity and launch planning. And based on that engagement, would you anticipate a more gradual build or could you see very rapid uptake if it's approved?

具體來說，我想知道您是否可以進一步討論與 KOL 倡議團體和付款人的互動，以及這對市場接受度和發布計劃有何啟示。基於這種參與，您是否預計會採取更漸進的建設方式，或者如果獲得批准，是否會看到非常迅速的吸收？

Thank you, Patrick. Kumar, on pitolisant HD?

謝謝你，派崔克。庫馬爾 (Kumar)，在 pitolisant HD 上嗎？

On pitolisant HD, we are on track to initiate two Phase 3 studies, one in narcolepsy and one in idiopathic hypersomnia in the fourth quarter of this year. At this stage, what I can say, Patrick, is that it's going to be a standard randomized double-blind placebo controlled parallel arm study. We are going to provide more information on the endpoint, the recruitment rate, and all of the other things as we approach the study initiation.

對於 Pitolisant HD，我們計劃於今年第四季啟動兩項 3 期研究，一項針對發作性睡病，另一項針對特發性嗜睡症。在這個階段，派崔克，我可以說的是，這將是一項標準的隨機雙盲安慰劑對照平行臂研究。隨著研究的開始，我們將提供更多關於終點、招募率以及所有其他事項的資訊。

Yeah, so I would say, standard trial design and then also in addition, looking at sort of novel endpoints, fatigue and narcolepsy, sleep inertia and IH to pursue a differentiated label in that regard. With regards to opportunities for ZYn002 to go to market, a lot of work has started. Adam, have a few thoughts on that?

是的，所以我想說，標準試驗設計，此外，還要研究新的終點，疲勞和嗜睡症，睡眠慣性和 IH，以在這方面追求差異化標籤。關於ZYn002進入市場的機會，很多工作已經開始。亞當，對此有什麼想法嗎？

Yeah, and actually, thanks for the question. I'll just go straight to the community and I think you mentioned receptiveness to new therapies. I mean, this is a very close knit and tight community, typically, what you see in rare disease, but especially so here because these are kids that are suffering from a range of symptoms across several domains: physical manifestation, cognitive impairment, as well as well as behavioral symptoms.

是的，實際上，感謝您的提問。我將直接進入社區，我認為您提到了對新療法的接受度。我的意思是，這是一個非常緊密和嚴密的社區，通常你在罕見疾病中看到這種情況，但在這裡尤其如此，因為這些孩子患有多個領域的一系列症狀：身體表現、認知障礙以及行為症狀。

They're very well aware of any treatment that's being developed that could potentially benefit their kids and so we would expect very high awareness and high receptivity when we come to market. In terms of go-to-market model, yeah, as Jeff said, our plans are underway. We're continuing to have discussions across the community with different stakeholders and really ensure that we are prepared for a success.

他們非常清楚正在開發的任何治療方法都可能使他們的孩子受益，因此，當我們進入市場時，我們期望獲得很高的認知度和接受度。就市場進入模式而言，是的，正如傑夫所說，我們的計劃正在進行中。我們將繼續與社區內的不同利害關係人進行討論，確保我們為成功做好準備。

Yeah, and I would just say, I think, this is what we do at Harmony, engaging with rare disease communities. We really have a -- I think a best-in-class, a world class patient advocacy team, and a cross functional team kind of working on our go-to-market strategy and that opportunity. So thanks.

是的，我想說，我認為這就是我們在 Harmony 所做的事情，與罕見疾病社群合作。我們確實擁有——我認為是一流的、世界一流的患者權益團隊，以及一個跨職能團隊，致力於我們的市場進入策略和機會。所以謝謝。

Great. Thanks so much.

偉大的。非常感謝。

Jason Gerberry, Bank of America.

美國銀行的 Jason Gerberry。

This is Bob (inaudible) for Jason Gerberry. A couple of questions from us focused on Zygel for Fragile X syndrome. First, based on prior CONNECT data, how are you modeling patient adherence to therapy if the drug replicates the subgroup data with FMR1 gene methylation. And specifically, what percent of patients do you expect to stay on drug given response rates versus what percent of patients might be expected to discontinue due to a lack of response?

我是 Bob（聽不清楚），代表 Jason Gerberry 發言。我們提出的幾個問題主要集中在治療脆性 X 症候群的 Zygel 上。首先，基於先前的 CONNECT 數據，如果藥物複製了 FMR1 基因甲基化的亞群數據，您如何模擬患者對治療的依從性。具體來說，考慮到治療反應率，您預計有多少百分比的患者會繼續服用該藥物，以及有多少百分比的患者可能會因缺乏治療反應而停藥？

And then my second question is beyond achieving statistical significance on the social avoidance primary endpoint, what specific results from the key secondary endpoints like the irritability subscale or the caregiver global impression would give you the highest conviction in the data package for filing?

然後我的第二個問題是，除了在社交迴避主要終點上實現統計意義之外，關鍵次要終點（例如易怒分量表或照顧者總體印象）的哪些具體結果會讓您在歸檔資料包時獲得最高的信心？

Thank you for those questions. There was several questions in there. Probably I'll start with the last one in terms of beyond social avoidance, what else we anticipate, or what else we are monitoring. As we have disclosed, we are looking at several other behavioral symptoms. Obviously, social avoidance is the primary endpoint, but we're also looking at irritability behaviors, another core symptom in patients with Fragile X syndrome.

感謝您提出這些問題。其中有幾個問題。我可能會從最後一個問題開始，除了社交迴避之外，我們還預期什麼，或者我們還在監控什麼。正如我們所揭露的，我們正在研究其他幾種行為症狀。顯然，社交迴避是主要終點，但我們也關注易怒行為，這是脆性 X 症候群患者的另一個核心症狀。

And we saw a pretty good response on this domain of symptoms from the CONNECT study. And in fact, we recently presented data on irritability at the American Association of Neurology meeting in April this year, which was a podium presentation where patients exposed to three years for ZYN002 showed sustained and clinically meaningful response in irritability domain.

我們從 CONNECT 研究中看到對這一症狀領域的反應相當良好。事實上，我們最近在今年 4 月的美國神經病學協會會議上展示了有關易怒性的數據，這是口頭報告，其中接受 ZYN002 治療三年的患者在易怒性領域表現出持續且具有臨床意義的反應。

In terms of the safety, tolerability, discontinuation, and persistence on treatment, the ZYN002 product has very unique attributes, and we have discussed this in many forums in the past. The adherence rate is very high, and in fact over 90% of the patients who completed the randomized double blind study in the RECONNECT study, and also in the CONNECT study elected to participate in the long-term extension study, and in those patients we have data lasting for more than eight years, still continuing to use ZYN002, gaining efficacy, good benefits with the acceptable safety and tolerability profile.

在安全性、耐受性、停藥和治療持久性方面，ZYN002 產品具有非常獨特的屬性，我們過去在許多論壇上都討論過這個問題。依從率非常高，事實上，在 RECONNECT 研究和 CONNECT 研究中完成隨機雙盲研究的患者中，超過 90% 的患者選擇參與長期擴展研究，並且我們擁有這些患者超過八年的數據，他們仍在繼續使用 ZYN002，獲得了療效和良好的益處，並且具有可接受的安全性和耐受性。

Yeah. I don't think I understood your very first question on the model link between CONNECT and RECONNECT?

是的。我認為我沒有理解您關於 CONNECT 和 RECONNECT 之間的模型連結的第一個問題？

Yeah. I'm just asking about adherence rates and discontinuation rates, what is expected based on the prior CONNECT data?

是的。我只是問一下依從率和停藥率，根據先前的 CONNECT 資料預期會怎麼樣？

I sorry, I don't think I still understood that question. Apologies.

抱歉，我想我還是不明白這個問題。抱歉。

Like what percent of patients might be expected to discontinue the drug versus remain on the drug, based on response rates that you saw in the prior published CONNECT data?

根據您在先前發布的 CONNECT 數據中看到的反應率，預計有多少百分比的患者會停藥或繼續服用藥物？

Okay, got it. Sorry, I don't have the data off the top of my head, but I can certainly provide you that data. Sorry about that. Thank you.

好的，明白了。抱歉，我沒有現成的數據，但我當然可以提供給你這些數據。很抱歉。謝謝。

Yeah, no worries. And I just think overall very well tolerated, again, this is an innovative product. A little different than the oral cannabidiol that's sort of in the market for other indications as a transdermal gel in terms of the GI side effects and others. I think, overall, well tolerated. And Kumar will get back with that information.

是的，不用擔心。我認為整體來說耐受性非常好，這又是一個創新產品。就胃腸道副作用和其他方面而言，它與市場上用於其他適應症的透皮凝膠口服大麻二酚略有不同。我認為，整體而言，耐受性良好。庫馬爾將會回覆該訊息。

Next question?

下一個問題？

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Thanks for taking my question. Maybe two follow ups on prior comments. Firstly, with regards to the RECONNECT study, if Kumar, you could sort of remind us what was the placebo response in the CONNECT study, and what assumptions you've made for the RECONNECT study. You mentioned that there's a standard deviation that you're sort of watching for within which as long as the response stays. You feel good about it, if you could sort of elaborate what that range is.

感謝您回答我的問題。也許對之前的評論有兩次後續。首先，關於 RECONNECT 研究，Kumar，您能否提醒我們 CONNECT 研究中安慰劑反應是什麼，以及您對 RECONNECT 研究做出了哪些假設。您提到，存在一個標準差，只要反應保持不變，您就會對其進行觀察。如果您可以詳細說明該範圍，您會對此感到滿意。

And then with regards to the orexin space and the potential implication on WAKIX. We've heard from physicians that with the orexins bringing patients to normalized levels, it might actually allow patients to move to from polypharmacy to monotherapy. In that context and maybe increasing their scrutiny on just cost of medicines, have you thought about potentially looking at some sort of a prospective study evaluating the complementary mechanisms between orexins and WAKIX?

然後是關於食慾素空間及其對 WAKIX 的潛在影響。我們從醫生那裡聽說，食慾素可以使患者的食慾恢復正常水平，實際上可能使患者從多種藥物治療轉向單一療法。在這種背景下，也許他們會加強對藥品成本的審查，您是否考慮過進行某種前瞻性研究來評估食慾素和 WAKIX 之間的互補機制？

Ami, good morning. Thanks for your questions. Kumar, in terms of the CONNECT study and the findings.

阿米，早安。感謝您的提問。Kumar，就 CONNECT 研究及其結果而言。

Yeah, Ami, great question. Good morning. Thank you. So in terms of the placebo response for the CONNECT study, the data is published by Berry-Kravis et al in the Journal of Neurodevelopmental Disorders. Happy to share that paper. What we saw, the placebo response in the overall population was around 2.29 points on the placebo arm, and in patients with greater than 90% methylation, we saw a lower placebo response, around 1.99.

是的，阿米，這個問題問得好。早安.謝謝。因此，就 CONNECT 研究的安慰劑反應而言，數據由 Berry-Kravis 等人在《神經發育障礙雜誌》上發表。很高興分享這篇論文。我們看到，整體人群的安慰劑反應在安慰劑組約為 2.29 分，而在甲基化率超過 90% 的患者中，我們看到的安慰劑反應較低，約為 1.99。

And similarly, we saw an increase in the magnitude efficacy in patients with complete methylation. This again goes to the earlier point that I was making. In patients with complete methylation, they have a higher burden of symptoms. The mechanism of action of ZYN002 fits very well interaction with the endocannabinoid system and the greater magnitude of response.

同樣地，我們發現完全甲基化的患者的療效幅度有所提高。這又回到了我之前提出的觀點。對於完全甲基化的患者，他們的症狀負擔更重。ZYN002 的作用機制與內源性大麻素系統的相互作用以及更大規模的反應非常契合。

In terms of your question about the orexin and WAKIX prospective study, there is some early preclinical data to show synergistic effect between orexin and the receptor agonists and [H3] inverse agonists. We haven't shared that information. And just one final point I wanted to make is the study is over 90% powered to detect a 1-point placebo adjusted difference between the active and the placebo arms.

關於您提到的食慾素和 WAKIX 前瞻性研究的問題，有一些早期臨床前數據顯示食慾素與受體激動劑和 [H3] 反向激動劑之間存在協同作用。我們尚未分享該資訊。最後我想說的一點是，這項研究有超過 90% 的功效檢測出活性組和安慰劑組之間 1 點安慰劑調整差異。

Yeah, so I mean, I think, in terms of your question about the orexin landscape, obviously, we're following the programs closely and looking at -- ultimately, it's overall kind of risk benefit and I think durability of response and understanding obviously orexins working through kind of wakefulness and how the mechanism of action of WAKIX working through histamine.

是的，所以我的意思是，我認為，就你關於食慾素前景的問題而言，顯然，我們正在密切關注這些項目並觀察——最終，它的整體風險效益，我認為反應的持久性以及對食慾素通過某種覺醒發揮作用的理解，以及 WAKIX 的作用機制如何通過組胺發揮作用。

We have contemplated the opportunity of a synergistic mechanism and the opportunity of concomitant, even a combination type of approach further down in our pipeline, and that is something that that we have contemplated to possibly address the opportunity of lower doses of orexin agonist, supported by pitolisant working through a synergistic mechanism. In the meantime, we focus on advancing the next-gen pitolisant and products and continue to grow the WAKIX-based business.

我們已經考慮過協同機制的機會，以及伴隨機制的機會，甚至是我們後續研發過程中的組合方法，我們已經考慮過透過協同機制支持匹托利桑來解決較低劑量食慾素激動劑的機會。同時，我們專注於推進下一代 Pitolisant 和產品，並繼續發展基於 WAKIX 的業務。

Thank you.

謝謝。

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

謝謝，我沒有其他問題。現在我想將電話轉回去，以便大家做最後發言。

Thank you, Madison, and thanks, everyone for joining our call this morning and for your interest in Harmony Biosciences. Have a great rest of your day.

謝謝你，麥迪遜，也謝謝大家今天早上參加我們的電話會議，以及對 Harmony Biosciences 的關注。祝您今天剩餘的時間過得愉快。

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

這確實結束了今天的 Harmony Biosciences 2025 年第二季財務業績電話會議。現在您可以斷開線路並享受美好的一天。