Harmony Biosciences Holdings Inc (HRMY) 2024 Q2 法說會逐字稿

Good morning. My name is Todd, and I will be your conference operator today. At this time, I would like to welcome everyone to Harmony Biosciences second quarter 2024 financial results conference call. (Operator Instructions) Please be advised that today's conference may be recorded. (Operator Instructions) I will now turn the call over to Brennan Doyle, Head of Investor Relations. Please go ahead.

早安.我叫托德，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技2024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）我現在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 2024 financial results and provide a business update. Before we start, I encourage everyone to go to the investor 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 in our life cycle, we believe non-GAAP financial results better represent the underlying business performance.

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 的 2024 年第二季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。

Our speakers today on the call are Dr. Jeff Dayno, President and CEO; Jeffrey Dirks, 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執行長 Jeff Dayno 博士；傑弗瑞‧德克斯，首席商務官； Kumar Budur 博士，首席醫療和科學官；財務長兼首席行政官 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 detail.

提醒一下，我們今天將根據我們當前的期望和信念做出前瞻性聲明。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陳述的義務。我們鼓勵您查閱我們向 SEC 提交的文件中引用的風險因素，以了解更多詳細資訊。

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

我現在想把電話轉給傑弗瑞·戴諾醫生。傑夫？

Thank you, Brendan, and thanks, everyone, for joining our conference call today. Q2 was another very productive quarter for the team at Harmony, delivering another quarter of strong revenue WAKIX and continued advancement in our late stage clinical development programs, highlighted by the significant progress made on our next-generation pitolisant high dose or pitolisant HD development program, formally referred to as NG2.

謝謝布倫丹，也謝謝大家今天參加我們的電話會議。第二季度對於Harmony 團隊來說是另一個非常富有成效的季度，WAKIX 又實現了強勁的收入季度，並在我們的後期臨床開發項目中持續取得進展，其中我們的下一代pitolisant 高劑量或pitolisant HD開發案取得的重大進展凸顯了這一點，正式稱為 NG2。

During our Q1 earnings call, we shared the initial pilot PK data for the pitolisant gastro resistant or pitolisant GR program, formerly referred to as NG1, along with a development plan as the first part of our pitolisant lifecycle management activities.

在第一季財報電話會議上，我們分享了pitolisant胃抗性或pitolisant GR專案（以前稱為NG1）的初始試點PK數據，以及作為我們pitolisant生命週期管理活動第一部分的開發計劃。

This quarter, we are excited to provide an update on our pitolisant HD program with a targeted to do to date in 2028 and a provisional patent filed out to 2044, providing us the opportunity to extend the pitolisant franchise to the mid 2040s with durable long-term revenue generation.

本季度，我們很高興提供Pitolisant HD 計劃的最新信息，目標是在2028 年完成，並在2044 年提交臨時專利，這使我們有機會將Pitolisant 特許經營權延長到2040 年代中期，並具有持久的長期效果。

First let me provide some color regarding the reasons why we are excited about advancing this program because of the unmet medical needs in the narcolepsy community that the pitolisant HD is designed to address.

首先，讓我提供一些關於我們為何對推進該計劃感到興奮的原因，因為 Pitolisant HD 旨在解決發作性睡病社區未得到滿足的醫療需求。

Later in the call, Kumar will share some of the initial pilot PK data and a few other details from the pitolisant HD development program. WAKIX offers a strong overall benefit risk profile for patients living with narcolepsy, has brought a meaningful enhancement to the market as the first and only non-scheduled treatment indicated for both excessive daytime sleepiness or EDS and cataplexy and has been extremely successful in the market.

稍後在電話會議中，Kumar 將分享一些初步試點 PK 數據以及pitolisant HD 開發計劃的一些其他細節。WAKIX 為發作性睡病患者提供了強大的整體獲益風險概況，作為第一個也是唯一一個針對白天過度嗜睡或EDS 和猝倒的非定期治療，為市場帶來了有意義的增強，並且在市場上取得了極大的成功。

But given the nature of narcolepsy as a chronic neurological disorder with difficult to treat symptoms, there still remain unmet needs and opportunities for continued innovation. For pitolisant GR and HD, the innovation is more focused on the continued unmet needs in the narcolepsy market and what we can do to address those needs.

但考慮到發作性睡病作為一種慢性神經系統疾病且症狀難以治療的性質，仍有未滿足的需求和持續創新的機會。對於pitolisant GR和HD，創新更側重於發作性睡病市場持續未滿足的需求以及我們可以採取哪些措施來滿足這些需求。

First, we know that greater than 75% of narcolepsy patients experienced residual symptoms while on treatment. And could benefit from a treatment with greater efficacy. This is why we are pursuing a high dose pitolisant formulation that also has an optimized PK profile to drive greater efficacy to address this need in the market.

首先，我們知道超過 75% 的發作性睡病患者在治療期間出現殘留症狀。並且可以從更有效的治療中受益。這就是為什麼我們正在尋求一種高劑量的 Pitolisant 製劑，該製劑還具有優化的 PK 特性，以提高功效來滿足市場的這一需求。

Second, about 60% of patients living with narcolepsy experienced fatigue, which is a different symptom than EDS and a common symptom in chronic neurological diseases with a higher dose at the pitolisant and based on the positive signals that we saw in both EDS and fatigue with pitolisant in our Phase 2 proof-of-concept study in Type 1 myotonic dystrophy or DM1, we plan to pursue a fatigue indication for pitolisant HD in patients with narcolepsy, as well as other neurological diseases such as DM1.

其次，大約60% 的發作性睡病患者經歷了疲勞，這是與EDS 不同的症狀，也是慢性神經系統疾病的常見症狀，需要較高劑量的Pitolisant，並且基於我們在EDS 和疲勞中看到的正向訊號在我們針對 1 型強直性肌肉營養不良症或 DM1 的 2 期概念驗證研究中，我們計劃在發作性睡病以及其他神經系統疾病（例如 DM1）患者中尋求 Pitolisant HD 的疲勞適應症。

Next, as we explained for our pitolisant GR program, a driving force behind the gastro resistant coding is the fact that about 90% of patients with narcolepsy experienced GI symptoms such as nausea, dyspepsia and abdominal discomfort. There is a mechanistic rationale for this especially in patients with NT1 or Type 1 narcolepsy related to the Orexin deficiency since orexin has effects on the vagus nerve in the brain, which is a central controller of gut motility.

接下來，正如我們對pitolisant GR項目所解釋的那樣，胃抵抗性編碼背後的驅動力是這樣一個事實：約90%的發作性睡病患者經歷過胃腸道症狀，如噁心、消化不良和腹部不適。這有一個機械原理，特別是對於與食慾素缺乏相關的 NT1 或 1 型發作性睡病患者，因為食慾素對大腦中的迷走神經有影響，而迷走神經是腸道運動的中央控制器。

In addition to the underlying disease mechanism, one out of five patients on narcolepsy medications experienced GI side effects related to the common narcolepsy treatments that are used. WAKIX is well tolerated with a low incidence of nausea, but the gastro resistant coating feature is designed to address the predisposition to GI symptoms in patients with narcolepsy, as well as the GI tolerability issues patients have experienced with other narcolepsy treatments.

除了潛在的疾病機制之外，五分之一的服用發作性睡病藥物的患者會出現與常用的發作性睡病治療相關的胃腸道副作用。WAKIX 具有良好的耐受性，噁心發生率低，但耐胃塗層功能旨在解決發作性睡病患者的胃腸道症狀傾向，以及患者在接受其他發作性睡病治療時遇到的胃腸道耐受性問題。

Taken together, the higher dose, optimized PK profile, gastro resistant feature and our plan to pursue additional indications would address significant unmet needs in patients with narcolepsy and position pitolisant HD as a meaningfully differentiated product and result in a differentiated label compared to WAKIX.

總而言之，更高的劑量、優化的PK 曲線、胃耐受特性以及我們追求其他適應症的計劃將解決發作性睡病患者未滿足的重大需求，並將pitolisant HD 定位為有意義的差異化產品，並導致與WAKIX 相比的差異化標籤。

With a provisional patent filed and potential IP out to 2044 and a target to do to date in 2028, this gives us an opportunity to introduce a differentiated product prior to WAKIX LOE in 2030, to extend the pitolisant franchise for the mid 2040s and drive durable, long-term revenue generation.

臨時專利申請和潛在智慧財產權的截止時間為2044 年，迄今為止的目標是2028 年，這使我們有機會在2030 年WAKIX LOE 之前推出差異化產品，將Pitolisant 特許經營權延長至2040 年代中期並推動耐用，長期創收。

Our commercial team conducted preliminary market research based on the target product profile for pitolisant HD. And initial results suggest that the features I described to you would be of real interest to patients be viewed as offering meaningful benefits by health care professionals and perceived as clinically superior compared to WAKIX by payers.

我們的商業團隊根據pitolisant HD 的目標產品概況進行了初步市場研究。初步結果表明，我向您描述的功能將真正引起患者的興趣，醫療保健專業人員認為這些功能提供了有意義的益處，付款人認為與 WAKIX 相比在臨床上更優越。

To round out our sleep wake franchise, we were very pleased with the FDA approval of WAKIX for EDS in pediatric narcolepsy patients ages six years and older, and we're excited to launch this new indication into the market on July 1.

為了完善我們的睡眠覺醒特許經營權，我們非常高興 FDA 批准 WAKIX 用於 6 歲及以上兒科發作性睡病患者的 EDS，我們很高興於 7 月 1 日將這一新適應症推向市場。

As a reminder, the pediatric narcolepsy data, along with data from the ongoing Phase 3 TEMPO study in Prader-Willi syndrome keeps us on track toward obtaining pediatric exclusivity, and an additional six months of regulatory protection on the back end of our longest patent, which would take us to September 2030.

提醒一下，兒科發作性睡病數據以及正在進行的普瑞德-威利綜合徵TEMPO 3 期研究的數據使我們有望獲得兒科獨家專利權，並在我們最長的專利後端獲得額外六個月的監管保護，這將帶我們到 2030 年 9 月。

We are on track to submit an sNDA for idiopathic hypersomnia later this year and are very excited about our potential best-in-class Orexin-2 agonist program for TPM-1116. We are working with our partner Bioprojet, and are on track towards filing an IND mid-2025 and then initiating first-in-human studies, second half of 2025.

我們預計在今年稍後提交針對特發性嗜睡症的 sNDA，並且對我們潛在的同類最佳的 TPM-1116 Orexin-2 激動劑項目感到非常興奮。我們正在與合作夥伴 Bioprojet 合作，預計在 2025 年中期提交 IND，然後在 2025 年下半年啟動首次人體研究。

Beyond our strong sleep wake franchise, we are also advancing late-stage programs in our other two franchises, neuro behavioral and rare epilepsy. Harmony has expanded its pipeline and diversified its portfolio that now includes three orphan rare CNS franchises, each one of which has peak sales opportunities of $1 billion to $2 billion.

除了我們強大的睡眠喚醒特許經營權之外，我們還在其他兩個特許經營權（神經行為和罕見癲癇）中推進後期項目。Harmony 擴大了其產品線並使其產品組合多元化，目前包括三個孤兒稀有 CNS 特許經營權，每個特許經營權的峰值銷售機會為 10 億至 20 億美元。

I want to highlight that our pipeline now has eight assets advancing across 13 development programs, and three of them are in Phase 3 with a fourth Phase 3 trial to begin later this year. Importantly, this pipeline is poised to deliver at least one new product or indication launch each year over the next five years. This, along with pitolisant HD PDUFA for date targeted for 2028 translates into the potential for significant, durable, long term value creation out beyond 2040. Kumar will be providing you updates on our development programs later in the call.

我想強調的是，我們的管道現在有 8 個資產正在推進，涉及 13 個開發項目，其中三個處於第三階段，第四個第三階段試驗將於今年稍後開始。重要的是，該管道準備在未來五年內每年至少推出一種新產品或適應症。這與 2028 年目標日期的pitolisant HD PDUFA 一起轉化為 2040 年以後創造重大、持久、長期價值的潛力。庫馬爾將在稍後的電話會議中向您提供有關我們開發計劃的最新資訊。

While we advance our pipeline programs, we remain focused on execution across the company and delivered another solid quarter with WAKIX net revenue of $172.8 million, representing 29% growth year-over-year. With these strong results, we are once again reiterating our 2024 net revenue guidance of $700 million to $720 million and we remain confident that WAKIX represents a $1 billion-plus market opportunity in narcolepsy alone, and we are well on our way.

在推進管道計劃的同時，我們仍然專注於整個公司的執行，並實現了又一個穩健的季度，WAKIX 淨收入達到 1.728 億美元，同比增長 29%。憑藉這些強勁的業績，我們再次重申 2024 年 7 億至 7.2 億美元的淨收入指導，我們仍然相信 WAKIX 僅在發作性睡病領域就代表了超過 10 億美元的市場機會，而且我們正在穩步前進。

What reinforces our confidence in the durability of the WAKIX franchise is the news we shared earlier this morning regarding the WAKIX polymorph patent being upheld once again after the second and final attempt to challenge the patent. Late last week, the US Patent and Trademark Office or USPTO issued its final denial of the petition for re-examination of the wake six patent, which was filed by a short seller.

今天早上早些時候我們分享的消息增強了我們對 WAKIX 特許經營權持久性的信心，即在第二次也是最後一次挑戰該專利後，WAKIX 多晶型物專利再次得到維持。上週晚些時候，美國專利商標局（USPTO）最終駁回了賣空者提交的喚醒六項專利複審申請。

We have always stood by WAKIX and our intellectual property. This reexamination request represented the second attempt to challenge the WAKIX patent and in its decision the USPTO stated and I quote "this decision is final and non-appealable" [end quote].

我們始終支持 WAKIX 和我們的知識產權。該複審請求代表了對 WAKIX 專利提出質疑的第二次嘗試，美國專利商標局在其決定中表示，我引用「該決定是最終決定，不可上訴」[引用結束]。

We remain very confident in the strength of our patents. The validity of the patent portfolio and our ability to rigorously enforce the intellectual property rights, protecting WAKIX. This bolsters our confidence in the durability of that the pitolisant franchise with the PDUFA date for pitolisant GR in 2026 of the target PDUFA date for pitolisant HD in 2028, the IP for WAKIX out to 2030 and provisional patents filed for pitolisant GR, HD out to 2044. This puts us in a solid position to extend the pitolisant franchise out to the mid 2040s.

我們對我們的專利實力仍然充滿信心。專利組合的有效性以及我們嚴格執行智慧財產權以保護 WAKIX 的能力。這增強了我們對pitolisant特許經營權持久性的信心，其中pitolisant GR的PDUFA日期為2026年，pitolisant HD的目標PDUFA日期為2028年，WAKIX的智慧財產權到2030年，pitolisant GR、HD的臨時專利申請到2044.這使我們處於有利地位，可以將皮托利森特的特許經營權延長至 2040 年代中期。

We also remain active in business development with the goal of building out our pipeline even further. With approximately $434 million in cash, cash equivalents and investments as of June 30, we are in a solid financial position to execute on additional BD opportunities that are consistent with our growth strategy and offer the potential to drive further value in our overall business.

我們也持續積極開展業務發展，目標是進一步擴大我們的管道。截至 6 月 30 日，我們擁有約 4.34 億美元的現金、現金等價物和投資，財務狀況穩健，可以執行與我們的成長策略一致的額外 BD 機會，並有可能進一步推動我們整體業務的價值。

Lastly, we look forward to hosting our inaugural Investor Day on October 1, in New York City, where we will have an opportunity to highlight our robust late-stage pipeline and share some new data with you.

最後，我們期待於 10 月 1 日在紐約舉辦首屆投資者日，屆時我們將有機會專注於我們強大的後期研發管線，並與您分享一些新數據。

With that, I will turn the call over to Jeffrey Dirks, our Chief Commercial Officer, for an update on our commercial performance. Jeff?

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

Thanks, Jeff. We saw another solid quarter of continued commercial progress for WAKIX in the second quarter, highlighted by continued product adoption and growth in our underlying business fundamentals. Net sales for the quarter were $172.8 million, representing 29% growth from the same quarter prior year.

謝謝，傑夫。我們在第二季度看到 WAKIX 又一個堅實的季度持續商業進展，突出表現在產品的持續採用和我們的基礎業務基本面的成長。該季度淨銷售額為 1.728 億美元，較去年同期成長 29%。

The solid net sales performance in Q2, reaffirms our confidence in our net sales guidance of $700 million to $720 million for the full year 2024. We saw continued growth in the average number of patients on WAKIX and the WAKIX prescriber base, both facilitated by favorable market access as seen on slide 4 and 5.

第二季穩健的淨銷售額表現重申了我們對 2024 年全年 7 億至 7.2 億美元淨銷售額指引的信心。我們看到 WAKIX 的平均病患數量和 WAKIX 處方者基礎持續成長，這都得益於有利的市場准入（如投影片 4 和 5 所示）。

The average number of patients on WAKIX increased to approximately 6,550 in the second quarter. We are extremely pleased with the sequential increase of approximately 250 patients from what we reported last quarter and the durable growth in year five of our rare orphan commercialization.

第二季 WAKIX 的平均病患人數增加至約 6,550 名。我們對上季度報告的患者數量連續增加約 250 名患者以及罕見孤兒藥商業化第五年的持續增長感到非常高興。

Growth in average patients in Q2 was in line with our expectations and reaffirms our confidence in our guidance of approximately 7,000 average patients by the end of the year.

第二季度平均患者數量的增長符合我們的預期，並重申了我們對年底前約 7,000 名平均患者的指導的信心。

We also saw the WAKIX prescriber base increase again in the second quarter. We're seeing continued growth in the WAKIX prescriber base beyond the OxyBate REMS enrolled health care professionals, and we're approaching 40% penetration in this segment of approximately 5,000 health care professionals at the end of the second quarter.

我們也看到 WAKIX 處方者基數在第二季再次增加。我們看到，除了OxyBate REMS 註冊的醫療保健專業人員之外，WAKIX 處方者群體也在持續增長，到第二季度末，我們在這一約5,000 名醫療保健專業人員的細分市場中的滲透率接近40%。

This segment of healthcare professionals represents an insulated group of prescribers and patients from the OxyBate that we continue to tap into each quarter to drive performance. The growth in this segment demonstrates WAKIX is broadening the branded writer segment beyond the OxyBate by providing a meaningfully differentiated product profile and one that offers broad clinical utility across the entire narcolepsy treating health care professional universe.

這部分醫療保健專業人員代表了與 OxyBate 無關的處方者和患者群體，我們每季都會繼續利用他們來提高績效。此細分市場的成長表明，WAKIX 正在透過提供有意義的差異化產品概況以及在整個發作性睡病治療醫療保健專業領域提供廣泛臨床實用性的產品概況，將品牌作家細分市場擴大到OxyBate 之外。

Coupled with the growth we're seeing beyond the OxyBate REMS enrolled health care professionals, we continue to see utilization of WAKIX among the approximately 4,000 OxyBate REMS enrolled healthcare professionals, even with the availability of new generic OxyBate options.

加上我們看到 OxyBate REMS 註冊的醫療保健專業人員之外的成長，我們繼續看到約 4,000 名 OxyBate REMS 註冊的醫療保健專業人員使用 WAKIX，即使有新的通用 OxyBate 選項可用。

We're highly penetrated within this prescriber audience and see WAKIX being prescribed to additional narcolepsy patients each quarter in this segment. As we've shared during previous earnings calls, our ability to call in the broad approximately 9,000 narcolepsy treating health care professional audience allows us to tap into the full diagnosed narcolepsy patient opportunity, giving us confidence in the $1 billion-plus opportunity for WAKIX in narcolepsy.

我們在這一處方者受眾群體中的滲透率很高，並且每個季度都會看到該細分市場中向更多的發作性睡病患者開出 WAKIX 處方。正如我們在先前的財報電話會議上所分享的那樣，我們能夠召集大約9,000 名治療嗜睡症的醫療保健專業觀眾，這使我們能夠利用全面診斷的嗜睡症患者的機會，使我們對WAKIX 在10 億美元以上的機會充滿信心。

Supporting the growth in patients and prescribers is our favorable market access and formulary coverage for WAKIX. We've seen no changes to the overall broad payer coverage for WAKIX over the past year with the introduction of new branded and generic options. And we believe we are well positioned to support future growth.

支持患者和處方者成長的是我們對 WAKIX 有利的市場准入和處方覆蓋範圍。在過去一年中，隨著新品牌和通用選項的推出，WAKIX 的整體廣泛付款人覆蓋範圍並沒有改變。我們相信我們有能力支持未來的成長。

As we are closing out another solid quarter of performance, we are excited to receive the news of the approval of WAKIX so the treatment of excessive daytime sleepiness at pediatric narcolepsy patients, six years and older on June 21.

隨著我們即將結束又一個堅實的季度業績，我們很高興收到 WAKIX 於 6 月 21 日獲得批准的消息，用於治療 6 歲及以上小兒發作性睡病患者的白天過度嗜睡。

WAKIX now represents the first and only non-scheduled treatment option for pediatric narcolepsy patients. And importantly, all narcolepsy patients have EDS, so with this approval, we have the opportunity to access the full diagnosed pediatric narcolepsy patient opportunity.

WAKIX 現在代表了兒童發作性睡病患者的第一個也是唯一一個非預定治療選擇。重要的是，所有發作性睡病患者都有 EDS，因此透過此次批准，我們有機會獲得完整診斷的兒科發作性睡病患者的機會。

The pediatric narcolepsy opportunity is a small but meaningful opportunity. It represents approximately 5% of the diagnosed narcolepsy opportunity or approximately 4,000 patients. And this approval is contemplated in our full year 2024 net sales guidance.

小兒發作性睡病機會雖小但意義重大。它代表了大約 5% 的診斷為發作性睡病的機會或大約 4,000 名患者。我們的 2024 年全年淨銷售額指引中也考慮了這項批准。

Our commercial team was prepared for this approval and started our now approved outreach the week following the approval. Our field sales team was trained later that week and without educating healthcare professionals about the new indication starting July 1.

我們的商業團隊已為此批准做好準備，並在批准後一周開始我們現已批准的外展活動。我們的現場銷售團隊在本週稍後接受了培訓，但從 7 月 1 日開始，並未對醫療保健專業人員進行新適應症的教育。

Although it's still early, we are seeing positive indicators from the launch. We're getting very positive feedback and interest from the patient health care professional community and payers have begun add WAKIX for pediatric narcolepsy to their formularies within the first 30 days from approval.

儘管現在還為時過早，但我們已經看到了發布的積極跡象。我們從患者醫療保健專業社區獲得了非常積極的反饋和興趣，付款人已開始在批准後的前 30 天內將用於兒科發作性睡病的 WAKIX 添加到他們的處方中。

In summary, we had another strong quarter of durable growth and performance in net sales, patient adds and growth in prescribers of WAKIX. Reaffirming our full year net sales guidance and average patient guidance that we issued earlier this year.

總之，我們在淨銷售額、患者增加和 WAKIX 處方者成長方面又經歷了一個強勁的季度持久增長和業績。重申我們今年稍早發布的全年淨銷售額指引和平均病患指引。

With the addition of the pediatric narcolepsy approval for the treatment of EDS, coupled with the strong fundamental business in our adult narcolepsy, we're seeing good leading indicators and our underlying business fundamentals.

隨著兒科發作性睡病治療 EDS 的批准，加上我們成人發作性睡病的強勁基本業務，我們看到了良好的領先指標和基本業務基本面。

Heading into the third quarter, we anticipate the typical summer seasonality, a fewer patient visits, lower foot traffic and offices consistent with previous years and other chronically managed conditions. And we remain confident in continued growth in average patients and prescribers of WAKIX moving forward.

進入第三季度，我們預計將出現典型的夏季季節性，患者就診次數減少，人流量減少，辦公室和其他長期管理的情況與前幾年一致。我們對 WAKIX 的普通患者和處方者的持續增長仍然充滿信心。

I'm excited about our performance and confidence in WAKIX representing a potential $1 billion-plus opportunity in narcolepsy alone and we're well on our way.

我對我們的表現感到興奮，並對 WAKIX 充滿信心，僅在發作性睡病領域就代表了超過 10 億美元的潛在機會，而且我們正在穩步前進。

I would 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?

我現在想將電話轉給我們的首席醫療和科學官 Kumar Budur，討論我們臨床開發專案的進展。庫馬爾？

Thank you, Jeff. Good morning, everyone, and thank you for joining us today. We continue to make great progress in advancing our pipeline programs, several of which are in late-stage development. As Jeff mentioned, we now have 13 different development programs ranging from preclinical to registrational studies across eight different assets and under three distinct franchisors focused raise neuro indications with high unmet medical need.

謝謝你，傑夫。大家早安，感謝您今天加入我們。我們在推進管道專案方面繼續取得巨大進展，其中一些專案正處於後期開發階段。正如傑夫所提到的，我們現在有13 個不同的開發項目，從臨床前研究到註冊研究，涵蓋八個不同的資產，並在三個不同的特許經營商下，重點關注未滿足醫療需求的神經適應症。

Our full clinical development pipeline is shown on slide number 6. It is important to note that we currently have three ongoing Phase 3 registrational studies that are actively recruiting patients for three distinct indications and plan to start a fourth Phase 3 registration study in patients with LGS during this half of 2024.

我們完整的臨床開發流程如第 6 張投影片所示。值得注意的是，我們目前正在進行三項 3 期註冊研究，正在積極招募針對三種不同適應症的患者，並計劃在 2024 年下半年針對 LGS 患者啟動第四項 3 期註冊研究。

Starting with our sleep wake franchise, the pitolisant high-dose, or pitolisant HD program, it is an enhanced formulation of pitolisant designed to deliver an optimized PK profile along with the higher dose, GR coated and target unique symptoms. We conducted a pilot PK study with four different prototype formulations in a highway crossover study comparing the fourth prototype formulations, which WAKEX (inaudible) reference formulation at a dose trend of 35.6 milligrams, the highest labeled dose for WAKEX.

從我們的睡眠喚醒特許經營權、pitolisant 高劑量或pitolisant HD 計劃開始，它是pitolisant 的增強配方，旨在提供優化的 PK 曲線以及更高劑量、GR 塗層和針對獨特症狀的效果。我們在高速公路交叉研究中對四種不同的原型製劑進行了初步PK 研究，比較了第四種原型製劑，其中WAKEX（聽不清楚）參考製劑的劑量趨勢為35.6 毫克，這是WAKEX 的最高標籤劑量。

Based on the pilot PK data, we are pleased to advance this program forward. The preliminary data from the prototype formulations showed a meaningful differentiation with at least approximately 20% increase in relative bioavailability and a decrease in the variability compared to WAKIX.

根據試點 PK 數據，我們很高興推進該計劃。原型製劑的初步數據顯示出有意義的差異，與 WAKIX 相比，相對生物利用度至少增加了約 20%，變異性降低。

Alongside further work on ,formulation optimization, we will progress this program and study after 2 times the current highest labeled dose of WAKIX, where we expect to demonstrate a further increase in the relative bioavailability and decreasing variability in the PK profile.

除了進一步進行配方優化工作外，我們還將在 WAKIX 目前最高標記劑量的 2 倍後推進該計劃和研究，我們期望證明相對生物利用度的進一步增加和 PK 曲線的變異性的降低。

In addition, the GR coating is designed to address the predisposition to see a tolerability issue in patients with narcolepsy and in April to start at the beginning of the therapeutic dose range. Therefore, an optimized PK profile, along with the higher dose GR coating and targeting unique symptoms such as fatigue and narcolepsy, is expected to provide a differentiated label and product profile.

此外，GR塗層旨在解決發作性睡病患者的耐受性問題，並於四月開始治療劑量範圍。因此，優化的 PK 特性，加上更高劑量的 GR 塗層和針對疲勞和嗜睡症等獨特症狀，預計將提供差異化的標籤和產品特性。

We will pursue an abbreviated clinical development program based on the leading edge work, including establishing safety margins for pitolisant up to 180 milligrams in a repeat dose study and qualitative research study on fatigue in narcolepsy that were completed over the past couple of years to support pitolisant HD program. We are targeting PDUFA date, in 2028, provisional patents have been submitted with the potential for patent protection until 2044.

我們將在前沿工作的基礎上開展一項簡短的臨床開發計劃，包括在過去幾年完成的重複劑量研究和嗜睡症疲勞定性研究中確定 180 毫克的 pitolisant 安全裕度，以支持 pitolisant高清節目。我們的目標是 PDUFA 日期為 2028 年，已提交臨時專利，並有可能在 2044 年之前獲得專利保護。

Moving on to pitolisant gastros assistant our GR program, we are on track to initiate the dosing optimization study in the fourth quarter of this year and a pivotal bioequivalence study in the first quarter of 2025 with PDUFA 2026.

接下來，我們的 GR 計畫將由pitolisant gastros 輔助，我們預計在今年第四季啟動劑量優化研究，並在 2025 年第一季與 PDUFA 2026 啟動關鍵生物等效性研究。

For the idiopathic hypersomnia or IH program, we are on track to submit an sNDA in the fourth quarter this year. The submission will be based on the totality of the data generated from (inaudible) study, including data from the ongoing long-term extension study, which strongly supports pitolisant efficacy in patients with IH.

對於特發性嗜睡症或 IH 項目，我們預計在今年第四季提交 sNDA。該提交將基於（聽不清楚）研究產生的全部數據，包括正在進行的長期擴展研究的數據，該研究強烈支持 Pitolisant 對 IH 患者的療效。

We have also identified other supporting information that will be included in the sNADA, including real-world evidence from pitolisant use in idipathic hypersomnia in Europe to further strengthen our submission. We are optimistic and remain committed in bringing a new treatment option for patients living with IH.

我們還確定了將納入 sNADA 的其他支持訊息，包括來自歐洲特發性嗜睡症使用皮托利桑的真實世界證據，以進一步加強我們提交的材料。我們持樂觀態度，並繼續致力於為 IH 患者帶來新的治療選擇。

In our neuro behavioral franchise, we remain on track to report top line data from the Phase 3 reconnect registrational trials of ZYN002 in Fragile X syndrome in mid 2025. In the rare epilepsy franchise, patient enrollment continues in the EPX-100 Phase 3 ARGUS trial for Dravet Syndrome with the top line data expected in 2026.

在我們的神經行為特許經營中，我們仍有望在 2025 年中期報告 ZYN002 治療脆性 X 綜合徵的 3 期重新連接註冊試驗的主要數據。在罕見癲癇專營權中，針對 Dravet 症候群的 EPX-100 3 期 ARGUS 試驗繼續招募患者，預計將於 2026 年獲得頂線數據。

We are also preparing to initiate a Phase 3 study in LGS another rare and severe developmental epileptic encephalopathy with high unmet medical need later this year.

我們也準備在今年稍後針對 LGS 啟動一項 3 期研究，這是另一種罕見且嚴重的發育性癲癇性腦病，醫療需求未滿足。

In summary, we have made significant progress in advancing our late-stage pipeline across three distinct franchises. If successful this program could result in at least one new product or indication launch each year, or the next five years, along with the potential to help hundreds of thousands of patients across all the rare neurological disorders we are investigating.

總而言之，我們在推動三個不同專營權的後期研發管線方面取得了重大進展。如果該計劃成功，每年或未來五年可能會推出至少一種新產品或適應症，並有可能幫助數十萬名患者應對我們正在研究的所有罕見神經系統疾病。

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 their efforts and commitment in helping us to advance our development programs.

我謹代表 Harmony，感謝所有參與我們臨床試驗的患者及其家屬，以及臨床研究人員和現場工作人員，感謝他們為幫助我們推進開發項目所做的努力和承諾。

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 second quarter earnings release and filed our 10-Q where you'll find the details of our second quarter 2024 financial and operating results.

謝謝你，庫馬爾，大家早安。今天早上，我們發布了第二季度收益報告，並提交了 10-Q 報告，您可以在其中找到 2024 年第二季度財務和營運業績的詳細資訊。

Our financial performance is also shown on slides 10 through 13. We delivered another quarter of solid financial performance with continued double-digit top line growth, profitability and strong cash generation.

我們的財務表現也顯示在投影片 10 至 13 中。我們又一個季度實現了穩健的財務業績，營收持續實現兩位數成長，獲利能力和強勁的現金生成能力。

Our financial performance and profile, positions us well to continue advancing our growth strategy for the remainder of the year and beyond. We reported net revenues of $172.8 million compared to $134.2 million in the prior year quarter, representing a growth of 29%.

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。我們報告的淨收入為 1.728 億美元，而去年同期為 1.342 億美元，成長了 29%。

Performance in the second quarter reflects the continued strong underlying demand for WAKIX. We also reported growth in income and margin. Non-GAAP adjusted net income for the second quarter of 2024 was $60.6 million, or $1.5 per diluted share compared to $45.9 million or $0.76 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.

第二季的業績反映了 WAKIX 持續強勁的潛在需求。我們也報告了收入和利潤的成長。2024 年第二季非 GAAP 調整後淨利為 6,060 萬美元，即稀釋後每股收益 1.5 美元，去年同期為 4,590 萬美元，即稀釋後每股收益 0.76 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，了解 GAAP 與非 GAAP 業績的調整。

With respect to expenses during the second quarter of 2024, we incurred two one-time charges related to business development transactions in the quarter, which impacted the R&D expense line. We incurred a $25.5 million charge related to the upfront licensing fee paid as part of the 2024 Bioprojet sublicensing agreement for TTM-1116 and a $17.1 million IP and R & D charge related to the acquisition Epygenix.

就2024年第二季的費用而言，我們在該季度產生了兩項與業務開發交易相關的一次性費用，這影響了研發費用線。我們支付了 2550 萬美元的費用，這些費用與作為 2024 年 Bioprojet TTM-1116 分許可協議的一部分而支付的預授權費相關，以及與收購 Epygenix 相關的 1710 萬美元的知識產權和研發費用。

The IP R&D charge related to Epygenix reflects the upfront payment of $35 million, offset by assets acquired into transactions, primarily composed of a deferred tax of approximately $18 million.

與 Epygenix 相關的智慧財產權研發費用反映了 3,500 萬美元的預付款，被交易中收購的資產所抵消，主要由約 1,800 萬美元的遞延稅組成。

We structured both transactions with low upfront and success driven milestones. This allows us to efficiently use shareholder capital and focused future investments on advancing the development programs and reaching value inflection points.

我們以低預付款和成功驅動的里程碑來建立這兩項交易。這使我們能夠有效地利用股東資本，並將未來的投資重點放在推動發展計畫和達到價值轉折點。

We ended the second quarter with $434.1 million of cash, cash equivalents and investments on the balance sheet. the balance reflects continued strong cash generation, which provide us with financial flexibility to execute on business development and to opportunistically return capital to shareholders. They are share repurchase program.

第二季末，我們資產負債表上的現金、現金等價物和投資為 4.341 億美元。這一餘額反映了持續強勁的現金產生能力，這為我們提供了財務靈活性，以執行業務發展並伺機向股東返還資本。它們是股票回購計劃。

Looking ahead, we continue to expect quarter over quarter growth for the balance of the year. We do expect an impact of summer seasonality we typically experience in the third quarter. We are once again reiterating our net revenue guidance for 2024 $700 million to $720 million, highlighting our progress towards the $1 billion-plus opportunity in narcolepsy alone.

展望未來，我們繼續預期今年剩餘時間將較上季成長。我們確實預計第三季通常會受到夏季季節性的影響。我們再次重申 2024 年淨收入指引為 7 億至 7.2 億美元，強調我們僅在嗜睡症領域就創造了超過 10 億美元的機會。

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 closing, I am very proud of the accomplishments that were made by the Harmony team during Q2, including significant progress and continued advancement of the pitolisant HD development program toward an expected PDUFA date in 2028.

謝謝你，桑迪普。最後，我對 Harmony 團隊在第二季度的成就感到非常自豪，包括在 2028 年預計 PDUFA 日期前取得重大進展和持續推進pitolisant HD 開發計劃。

This, along with the USPTO's final decision upholding the validity of the WAKIX patent after two failed attempts to challenge the patent with IP out to 2030 puts us in a solid position to extend the pitolisant franchise out to the mid 2040s.

再加上美國專利商標局在兩次嘗試挑戰該專利至 2030 年失敗後維持 WAKIX 專利有效性的最終決定，使我們處於將 Pitolisant 特許經營權延長至 2040 年代中期的穩固地位。

Continued strong revenue generation for WAKIX with 29% growth year-on-year. The approval and launch of the pediatric narcolepsy indication for WAKIX. Advancement of our Phase 3 clinical trials for ZYN-002 in Fragile X syndrome. EPX-100 in Dravet syndrome and pitolisant in Prader-Willi syndrome, along with a fourth Phase 4 trial of EPX-100 on track to initiate later this year in Lennox-Gastaut syndrome.

WAKIX 持續強勁創收，較去年同期成長 29%。WAKIX 的兒科發作性睡病適應症已獲批准並上市。ZYN-002 治療脆性 X 症候群的 3 期臨床試驗取得進展。EPX-100 用於治療 Dravet 綜合徵，pitolisant 用於治療 Prader-Willi 綜合徵，EPX-100 的第四項 4 期試驗預計將於今年稍後啟動用於治療 Lennox-Gastaut 綜合徵。

And two business development deals, including the in-licensing of the Orexin-2 agonist, TPM-1116 with our partner Bioprojet, and the acquisition of Epigenix Therapeutics that brought in EPX-100 and establish an exciting rare epilepsy franchise for Harmony.

還有兩項業務發展交易，包括與我們的合作夥伴Bioprojet 獲得Orexin-2 激動劑TPM-1116 的許可，以及收購Epigenix Therapeutics，後者引入了EPX-100 並為Harmony 建立了令人興奮的罕見癲癇特許經營權。

We remain focused on execution, driven in the advancement of our late-stage pipeline, strategic in our approach to further build out our pipeline and committed to creating durable long-term value for our shareholders while bringing innovative treatments to market to help even more patients living with rare neurological diseases and unmet medical needs.

我們仍然專注於執行，推動我們後期管道的推進，採取策略性方法進一步建立我們的管道，並致力於為我們的股東創造持久的長期價值，同時將創新療法推向市場以幫助更多患者患有罕見的神經系統疾病和未滿足的醫療需求。

This concludes our planned remarks for this morning. 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?

我們今天早上的演講就到此結束。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？

(Operator Instructions)

（操作員說明）

François Brisebois, Oppenheimer.

弗朗索瓦·布里斯布瓦，奧本海默。

Hey, guys. Thanks for the questions, and congrats on the quarter. In terms of seasonality, you talked about the summer or the third quarter months to be kind of similar to what we've seen in the past. I think last year, the patient add average is actually very solid and strong and kind of kept going in the third quarter.

嘿，夥計們。感謝您的提問，並祝賀本季。就季節性而言，您談到夏季或第三季與我們過去所看到的有點相似。我認為去年的患者平均增加量實際上非常穩定和強勁，並且在第三季度繼續保持下去。

In the past, we have seen some drop. So is it something that could be downward from the second quarter? Or just help us understand a little bit more what you mean by saying that it's normal seasonality that you've kind of seen in terms of patient ads in the past years?

過去，我們看到了一些下降。那麼，是否會比第二季度下降？或者只是幫助我們更多地理解您所說的過去幾年在患者廣告方面看到的正常季節性是什麼意思？

Good morning, Frank, and thanks for the question. I will turn it over to Jeff Dirk to respond.

早安，弗蘭克，謝謝你的提問。我將把它交給傑夫·德克來回應。

Sure. Yes. So Frank, when we talk about typical summer seasonality really relates to fewer patient visits and the lower foot traffic. And that's more of a reflection on new patients versus existing patients. So we do anticipate typically a little bit lower in terms of the new patient starts, it happens with most chronically managed medications.

當然。是的。因此，弗蘭克，當我們談論典型的夏季季節性時，實際上與患者就診次數減少和人流量減少有關。這更反映了新患者與現有患者的對比。因此，我們確實預期新患者的起始人數通常會稍微低一些，大多數長期管理的藥物都會發生這種情況。

Most patients don't schedule their medication visits during the summer when they're on vacation and holiday. But we do anticipate continued growth as you've seen in the last four or five years of our commercialization. We are obviously reiterating our guidance at approximately 7,000 average patients by the end of the year.

大多數患者不會在夏季休假期間安排就診。但我們確實預計會持續成長，正如您在過去四、五年的商業化過程中所看到的那樣。我們顯然重申了我們對年底前平均約 7,000 名患者的指導。

And obviously, with the addition to the pediatric narcolepsy indication, that's going to help us support future growth as we continue to tap into this opportunity as the market allows around the typical seasonal dynamics.

顯然，隨著兒童嗜睡症適應症的增加，這將有助於我們支持未來的成長，因為我們將在市場允許典型季節性動態的情況下繼續利用這一機會。

That's helpful. And then on that note, you talked about, it's about 4,000 patients on the pediatric side. Do you expect penetration in that space in the pediatric population to be better or more difficult than the adult centers?

這很有幫助。關於這一點，您談到，兒科方面約有 4,000 名患者。您預計兒科族群在該領域的滲透會比成人中心更好還是更困難？

So, Franc, what I would say is that what we're seeing within the pediatric market is I would expect the pediatric patients to be added over a couple of years versus a bolus of patients, right? This is a brand-new audience for us, although there are WAKIX prescribers with knowledge of the product and its profile.

所以，Franc，我想說的是，我們在兒科市場看到的是，我預計兒科患者將在幾年內增加，而不是大量患者，對嗎？儘管 WAKIX 處方者了解該產品及其簡介，但對我們來說這是一個全新的受眾。

We have to go out and look at educating not only patients but more importantly, the parents and the caregivers about the profile. So, a little bit different than the adult population when we launch where there was sort of a bolus of patients looking for a new option.

我們必須走出去，不僅對病人進行教育，更重要的是對父母和照顧者進行個人資料教育。因此，與我們推出時的成年人群有點不同，當時有一大群患者在尋找新的選擇。

We're going to look to tap into this opportunity. I would anticipate probably a very similar patient penetration over time. But we're going to be looking to add these patients every single quarter as opposed to a large bolus that you anticipate in the third quarter or fourth quarter this year.

我們將尋求利用這個機會。我預計隨著時間的推移，患者滲透率可能會非常相似。但我們希望每季都會增加這些患者，而不是您預計今年第三季或第四季的大量患者。

Yes. And Franc, I would just add, as the first and only non-scheduled product approved for patients with narcolepsy, I think vaginas a strong type offering for pediatric ovals patients.

是的。我想補充一點，Franc，作為第一個也是唯一一個被批准用於發作性睡病患者的非定期產品，我認為陰道對於兒科橢圓形患者來說是一種強有力的產品。

Thank you.

謝謝。

Thanks, Frank.

謝謝，弗蘭克。

Charles Duncan, Cantor Fitzgerald.

查爾斯鄧肯，坎托菲茨杰拉德。

Morning, Jeff and team, congrats on a great quarter and appreciate taking the questions. I actually had a follow-up to that last question regarding pediatrics patient population. I'm wondering when you consider the prescriber base of the 4k oxybate patient prescribers versus the 5k non oxybate registered prescribers, where do you think the pediatric patient population exists more?

早安，傑夫和團隊祝賀這個季度的出色表現，並感謝回答問題。實際上，我對兒科患者群體的最後一個問題進行了跟進。我想知道，當您考慮 4k 羥丁酯患者處方者與 5k 非羥丁酯註冊處方者的處方者基礎時，您認為兒科患者群體更多存在於哪裡？

And then secondarily, in addition to penetration, what do you think about persistence? It would seem to me that persistence could be even greater in the pediatric patient population.

其次，除了滲透之外，您對持久性有何看法？在我看來，兒科患者的持久性可能更高。

Good morning, Charles. Thank you for your question. Jeff, thoughts on where these patients are coming from.

早上好，查爾斯。謝謝你的提問。傑夫，想想這些病人來自哪裡。

Sure. So Charles, we know there are about 1,100 health care professionals that manage that approximately 4,000 diagnosed pediatric narcolepsy patients. It probably skews a little more heavily to the oxybate REMS enrolled health care professionals because as you know, this is a very difficult lifelong neurologic disorder to treat and ultimately, these patients end up and some of those larger sleep centers.

當然。Charles，我們知道大約有 1,100 名醫療保健專業人員負責管理約 4,000 名被診斷為發作性睡病的兒科患者。它可能更偏向於參加羥丁酸快​​速眼科治療的醫療保健專業人員，因為如您所知，這是一種非常難以治療的終生神經系統疾病，最終，這些患者最終會進入一些較大的睡眠中心。

But the great news is of those 1,100 doctors that a good amount of those were already in our existing call plan. There already have familiarity with weak. So a lot of that is simply just getting in touch with the parents, caregivers and patients and bringing them in the office. And I think again, it's very early, but I would probably assume that we've seen very good persistency rates with WAKIX in adults.

但對於這 1,100 名醫生來說，好消息是，其中很大一部分已經在我們現有的呼叫計畫中。對弱已經有了熟悉。因此，許多工作只是與父母、照護人員和患者取得聯繫，並將他們帶到辦公室。我再次認為，現在還為時過早，但我可能會假設我們已經在成人中看到了非常好的 WAKIX 持續率。

So I would assume that the pediatric population may have the potential for equivalent or better persistence. As you know, WAKIX as Jeff shared, is a very ideally suited product profile for pediatric patients. It's a once daily oral tablet you take in the morning upon awakening.

因此，我認為兒科族群可能具有同等或更好的持久性的潛力。如您所知，Jeff 分享的 WAKIX 是一款非常適合兒科患者的產品。這是一種每日一次的口服藥片，您在早上醒來時服用。

So you don't have to worry about patients having to maybe go to the nurse during the day at school or have to schedule med visits for parents to drop off medicine and being announced because of treatment options. Certainly that profile really appeals to the doctors, but also the parents of these individuals.

因此，您不必擔心患者可能需要白天在學校去看護士，或者必須安排家長就診以送藥並因治療選擇而被告知。當然，這種個人資料確實吸引了醫生，也吸引了這些人的父母。

Excellent. Can I ask one quick pipeline question of Kumar? And that is regarding IH sNDA filing this this year. Are you waiting for any additional, call it, clinical data or experimental results to enable that filing.

出色的。我可以問 Kumar 一個快速的管道問題嗎？這就是關於今年 IH sNDA 備案的情況。您是否正在等待任何額外的臨床數據或實驗結果來啟用該歸檔。

And perhaps can you describe a little more the real world use that you're thinking about, including it. And finally, would you anticipate that to be a relatively quick turnaround. So maybe enabling on approval and launch by second half of next year?

也許您可以更多地描述您正在考慮的現實世界用途，包括它。最後，您是否預期這是一個相對較快的轉變。那麼也許會在明年下半年獲得批准並推出？

Hey good morning, Charles. Thanks for the question. First of all, we are on track to submit the sNDA by the end of this year. In terms of the evidence, as we have discussed in the past, the totality of the data from the infield study, the open-label part, randomized to period and also the long-term extension study, now it's almost close to a year since the study was completed.

嘿早上好，查爾斯。謝謝你的提問。首先，我們預計在今年年底之前提交 sNDA。就證據而言，正如我們過去所討論的，內場研究、開放標籤部分、隨機週期以及長期延伸研究的數據總量，現在已經接近一年了研究已經完成。

We still have about two-thirds of the patients who entered into the long-term extension study still participating study. Almost all of them have completed 12 months, about one-third of them have completed 18 months, and some of them are approaching 3 years. So this speaks to the persistence of efficacy and persistence on treatment and also the benign safety profile.

我們仍有大約三分之二進入長期擴展研究的患者仍在參與研究。幾乎所有的人都完成了12個月，大約三分之一的人完成了18個月，還有一些接近3年。因此，這說明了療效的持久性和治療的持久性以及良好的安全性。

In terms of the additional data, we are leveraging some real-world evidence data from neuro (inaudible) described in patients with Idiopathic Hypersomnia and we'll be leveraging this data to make a stronger submission. But at the end of the day, Charles, we strongly believe in the unique benefit risk proposition, pitolisant offers in patients with Idiopathic Hypersomnia with the currently available treatment option is a scheduled three control substance or off-label of controlled substance was pitolisant, which has a profile of nonscheduled drug with a very simple dosing regimen of taking once a day (inaudible) .

就附加數據而言，我們正在利用特發性嗜睡症患者神經（聽不清楚）所描述的一些真實世界證據數據，我們將利用這些數據來提出更有力的意見。但最終，查爾斯，我們堅信，pitolisant 為特發性嗜睡症患者提供的獨特的益處風險主張，目前可用的治療方案是預定的三種對照物質或標籤外對照物質是pitolisant，這具有非常簡單的給藥物方案（每天服用一次）的非定期藥物特徵（聽不清楚）。

Persistance information, very helpful. Thanks for taking the question.

持久性訊息，非常有幫助。感謝您提出問題。

Ami Fadia, Needham.

阿米法迪亞，尼達姆。

Hi, good morning. Congratulations on all the progress across the pipeline. My first question is for Kumar regarding the pitolisant high-dose formulation. Can you help us better understand how the increased exposure rate would translate into and higher efficacy and maybe more from a mechanistic rationale and maybe the occupancy and sort of how much, what is sort of the unmet need there? And how do you see a patient benefit during the course of the day with the higher dose formulation?

嗨，早安。祝賀整個管道取得的所有進展。我的第一個問題是向 Kumar 提出的關於 pitolisant 高劑量製劑的問題。您能否幫助我們更好地了解增加的暴露率如何轉化為更高的功效，也許更多地來自機械原理，也許還有佔用率和多少，那裡未滿足的需求是什麼？您如何看待較高劑量製劑在一天中對病人的益處？

Good morning, Ami. Thank you for the question. Yes, first of all, Ami, we are really excited with the data that we saw with pitolisant high dose formulation. We saw both an increase in relative fire availability and also decrease in interintuition variables. And also, as we have discussed earlier in the press release, we will be studying up to 2 times the highest (inaudible).

早上好，阿米。謝謝你的提問。是的，首先，Ami，我們對 Pitolisant 高劑量製劑的數據感到非常興奮。我們看到相對火力可用性的增加和直覺變數的減少。而且，正如我們之前在新聞稿中討論的那樣，我們將研究最高值的 2 倍（聽不清楚）。

We have a body of the evidence Ami to show a dose response with increasing pitolisant results increased FX size both (inaudible) and also some of the symptoms that we plan to target with pitolisant HD program, a fatigue in narcolepsy is higher (inaudible). So the combination of an optimal (inaudible) the highest dose, the gastro-resistant formulation, which is designed, which is widely prevalent to (inaudible) patients with narcolepsy.

我們有大量證據表明，隨著pitolisant結果的增加，劑量反應會增加FX大小（聽不清楚），而且我們計劃用pitolisant HD計劃針對一些症狀，發作性睡病的疲勞程度更高（聽不清楚）。因此，最佳（聽不清楚）最高劑量的組合，即設計的胃抗性製劑，在（聽不清楚）發作性睡病患者中廣泛流行。

The ability to start up the therapeutic dose range and finally, targeting the symptom for which there are no approved treatment offers a very unique product profile for our patients, and this product profile was very well received when Jeff Dierks and his team did market research.

啟動治療劑量範圍並最終針對尚未獲得批准的治療的症狀的能力為我們的患者提供了非常獨特的產品概況，當 Jeff Dierks 和他的團隊進行市場研究時，該產品概況非常受歡迎。

Jeff, do you want to add anything?

傑夫，你想補充什麼嗎？

Sure. So Ami, just from a commercial perspective, we did do some preliminary market research across about 100 narcolepsy patients, 25 with sleep specialists and health care professionals and seven pharmacy directors and payers just to get some feedback with the initial target product profile. And I think it's Kumar stated looking across those three audiences, what was coming out of the research was that this is a very meaningfully differentiated product profile and one that looks to be clinically superior than WAKIX, simply because the biggest unmet need that's in the marketplace is enhanced efficacy.

當然。所以，Ami，僅從商業角度來看，我們確實對大約100 名發作性睡病患者、25 名睡眠專家和醫療保健專業人員以及7 名藥房主管和付款人進行了一些初步市場研究，只是為了獲得有關初始目標產品概況的一些回饋。我認為Kumar 表示，縱觀這三位受眾，研究得出的結果是，這是一個非常有意義的差異化產品概況，並且在臨床上看起來比WAKIX 更優越，僅僅是因為市場上最大的未滿足需求是功效增強。

About 75% of patients that are on treatment, still report residual symptoms that impact their daily life. And so we know in a poly pharmacy market physicians and patients are looking for enhanced efficacy. Then the other second unmet need is really the untreated fatigue, which no product currently is approved for right now and data suggested up to 60% of narcolepsy patients also have untreated fatigue, which is very distinct and different from excessive daytime sleepiness.

約 75% 接受治療的患者仍報告影響日常生活的殘留症狀。因此我們知道，在綜合藥局市場中，醫生和患者都在尋求增強的療效。第二個未滿足的需求實際上是未經治療的疲勞，目前還沒有產品獲得批准用於治療這種情況，數據顯示高達60% 的發作性睡病患者也有未經治療的疲勞，這與白天過度嗜睡非常不同。

And then lastly, what we've seen in the literature as well as in research is more than 90% of people living with narcolepsy have GI disturbances, mostly attributed to their pathophysiology of their disease, but up to 20% of them also experienced GI issues such as nausea on their medication.

最後，我們在文獻和研究中看到，超過90% 的發作性睡病患者患有胃腸道紊亂，這主要歸因於他們疾病的病理生理學，但其中高達20% 的人也經歷過胃腸道紊亂藥物引起的噁心等問題。

So the combination of this profile addressing enhanced efficacy, untreated fatigue in the GI symptom with the gastro-resistant coating really seems to present a very clinically superior product, one that payers are going to be broadly covering and one that physicians really see as a very attractive treatment option for the vast majority of their patients.

因此，這種解決增強功效、胃腸道症狀中未經治療的疲勞與耐胃塗層的組合確實似乎提供了一種臨床上非常優越的產品，付款人將廣泛覆蓋該產品，並且醫生確實將其視為一種非常好的產品。

Great. Thank you. My second question is, of course, on the, with all of these different programs underway, those, obviously, going to be a fair amount of investment from the R&D front as these assets progress. Where is business development in terms of the company's priorities and what type of assets do you think would make sense to bring on? Would it be later-stage assets as opposed to in market assets, sorry, early-stage assets as opposed to in-market assets, if you can give us some color there. Thank you.

偉大的。謝謝。當然，我的第二個問題是，隨著所有這些不同的項目正在進行中，隨著這些資產的進展，這些顯然將是來自研發方面的相當數量的投資。就公司的優先事項而言，業務發展在哪裡？這是後期資產還是市場資產？ 抱歉，是早期資產還是市場資產，如果您能給我們一些說明的話。謝謝。

Sure. Ami, thanks for the question. I mean, business development continues, as Jeff mentioned, the priority for the company. We've done several transactions that we saw from the last year or so. We've done three transactions. And see, we've done them in a financial disciplined manner. We've looked at them at all at low upfront, success-driven milestones, overall.

當然。阿米，謝謝你的提問。我的意思是，正如傑夫所提到的，業務發展繼續是公司的首要任務。我們已經完成了去年左右看到的幾筆交易。我們已經完成了三筆交易。看，我們以財務紀律的方式完成了這些任務。總體而言，我們已經從低前期、成功驅動的里程碑角度審視了它們。

And the filters for us continue to be rare, since CNS looking at things that can help leverage a lot of the capabilities that we've already built as a company. And we think we have more programs in-house, we're building better and better capabilities that we can elaborate both on the clinical side as well as commercial. I don't know if you have any thoughts further?

我們的過濾器仍然很少見，因為 CNS 正在尋找可以幫助利用我們作為一家公司已經建立的許多功能的東西。我們認為我們有更多的內部項目，我們正在建立越來越好的能力，我們可以在臨床和商業方面進行詳細闡述。不知道你還有什麼想法嗎？

Yes, no. Good morning, Ami. I would just add that I think that the strategy that we've taken thus far in regards to business development with the strategic focus in orphan, rare neuro, how we build out sort of the three franchises that we have now with our main franchise in Sleep Wake, the neurobehavioral franchise and the Rare Epilepsy franchise we bought in.

是的，不是。早上好，阿米。我想補充一點，我認為我們迄今為止在業務發展方面採取的策略，策略重點是孤兒、稀有神經，我們如何建立我們現在擁有的主要特許經營權的三個特許經營權Sleep Wake、神經行為特許經營權和我們購買的罕見癲癇特許經營權。

I mean we see that strategy and opportunities in a similar vein going forward. And where we are now with regard to the three CNS franchises and doing it in a thoughtful and a prudent manner has set us up each of those with potential peak sales opportunities of $1 billion to $2 billion.

我的意思是，我們以類似的方式看到了未來的策略和機會。我們現在就 CNS 的三個特許經營權而言，以深思熟慮和謹慎的方式進行，為我們的每一個特許經營權創造了 10 億至 20 億美元的潛在高峰銷售機會。

We can potentially add to each of those franchises or if we see an opportunity sort of in an adjacent area in Neuro or Neuropsych Disorders, then we would contemplate that as well. We like our profile. We like the way we've approached it thus far. And we continue to take a similar approach going forward.

我們可能會增加每個特許經營權，或者如果我們在神經或神經精神疾病的鄰近領域看到機會，那麼我們也會考慮這一點。我們喜歡我們的個人資料。我們喜歡迄今為止的處理方式。我們今後將繼續採取類似的方法。

Got it. Thank you so much.

知道了。太感謝了。

Thank you, Ami.

謝謝你，阿米。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Thanks. Just a couple. So first on the high-dose formulation. Can you talk through the dosing in contrast to both the legacy formulation and GR. And what I'm wondering in particular is with the greater potency. Is there any risk at all that it could cross into controlled substance territory in terms of scheduling and what kind of, are you going to do the full suite of human abuse liability work there? So that's number one.

謝謝。只是一對。所以首先是高劑量配方。您能談談與傳統配方和 GR 相比的劑量嗎？我特別想知道的是具有更大的效力。在日程安排方面是否存在任何可能進入受管制物質領域的風險？所以這是第一。

And then number two, I might have missed this earlier, but you talked more about the the doctors who are not enrolled in the oxybate REMS. Can you talk about your penetration there and what your expectation is over time in terms of penetration into that portion of the physician audience? Thank you.

第二，我可能早些時候錯過了這一點，但您更多地談論了未參加 oxybate REMS 的醫生。您能談談您在那裡的滲透率以及隨著時間的推移，您對滲透到這部分醫生受眾的期望是什麼嗎？謝謝。

Yeah. Good morning, David. Thanks for your questions. Let me address part of the first one, and then I'll turn it over to Kumar for the next one. With regards to the potential for changing the abuse potential Pitolisant HD, David, this is to Pitolisant.

是的。早安，大衛。感謝您的提問。讓我先解決第一個問題的一部分，然後我將把下一個問題交給庫馬爾。關於改變 Pitolisant HD 濫用潛力的潛力，大衛，這是針對 Pitolisant 的。

So in terms of mechanistically, I mean the short answer is no. The higher dose does not change the mechanism with regards to the lack of abuse potential or abuse liability. So the program will not require further abuse liability studies.

所以從機制上來說，我的意思是簡短的答案是否定的。較高劑量不會改變關於缺乏濫用潛力或濫用傾向的機制。因此，該計劃不需要進一步的濫用傾向研究。

And then in terms of the dosing and with regards to Pitolisant GR, that is based on the demonstration of bioequivalence at equivalent doses to WAKIX within the current labeled range of 17.8% to 35.6%.

然後就劑量而言，就 Pitolisant GR 而言，這是基於在當前標記範圍 17.8% 至 35.6% 內與 WAKIX 等效劑量的生物等效性證明。

I'll turn it over to Kumar to comment on the plan with regards to the opportunity in the Pitolisant HD program and what the thinking is there.

我會將其轉交給 Kumar，以評論該計劃中有關 Pitolisant HD 計劃的機會以及其中的想法。

Sure. Thank you, Jeff. Hey. Good morning, Dave. Thanks for the question. Yes, there were like several parts to your questions. So let me address one after the other. Starting with the dosing regimen, I say the dosing regimens here will be different compared to the legacy (inaudible) program, and we will provide those details at a later point in time in terms of the dosage strength that we'll be posting. But as we said earlier, we will be studying up to 2 times, the highest rate of (inaudible) .

當然。謝謝你，傑夫。嘿。早上好，戴夫。謝謝你的提問。是的，您的問題有幾個部分。那麼，就讓我一講一講。從給藥方案開始，我說這裡的給藥方案與傳統（聽不清楚）計劃相比將有所不同，我們將在稍後的時間點根據我們將發布的劑量強度提供這些詳細資訊。但正如我們之前所說，我們將學習最多 2 次，最高的比率（聽不清楚）。

And the second question was around safety and the height. The safety profile, we have studied already as part of the leading edge work that we did in preparation for the pitolisant HD program. We did a multiple ascending dose study up to 180 milligrams of pitolisant high-dose study and established safety policy. The safety profile is very similar to the safety profile of WAKIX, including the impact on cardiovascular system. So there was no QDC impact even at 180 milligram repeat dose.

第二個問題是關於安全和高度。作為我們為pitolisant HD 專案做準備的前沿工作的一部分，我們已經研究了安全性。我們進行了多次遞增劑量研究，高達 180 毫克的pitolisant 高劑量研究，並制定了安全政策。安全性與 WAKIX 的安全性非常相似，包括對心血管系統的影響。因此，即使重複劑量為 180 毫克，也沒有 QDC 影響。

And in terms of abuse that as Jeff mentioned, that's not a concern because multiple studies in the preclinical arena have not shown any release of dopamine in nucleus action (inaudible) . That is the one that usually results in abuse potential, and we haven't seen that. And human abuse potential studies were done up to 6x times of the development, and we did not see anything. In fact, the development were very similar to placebo.

就傑夫提到的濫用而言，這不是一個問題，因為臨床前領域的多項研究並未顯示核子作用中多巴胺的任何釋放（聽不清楚）。這通常會導致濫用的可能性，但我們還沒有看到這種情況。人類虐待潛力研究進行了高達開發時間的 6 倍，但我們沒有看到任何結果。事實上，這項進展與安慰劑非常相似。

And the second part of the question to Jeff.

向傑夫提出問題的第二部分。

So David, I believe you're inquiring about the penetration within the non oxybate REMS and all health care professionals. And so within that audience, there's about 5,000 of those health care professionals. And what we saw in the second quarter that were approaching about 40% penetration within that audience. It's been a regular rhythm that we've been able to tap in and see growth within this segment.

大衛，我相信您正在詢問非氧酸鹽 REMS 和所有醫療保健專業人員的滲透情況。因此，在這些觀眾中，大約有 5,000 名醫療保健專業人員。我們在第二季度看到，該受眾群體的滲透率接近 40%。這是我們能夠利用並看到該細分市場成長的常規節奏。

With respect to goal for penetration, I don't necessarily have a goal per se in mind, but I do believe there is still ample room to grow in this area or we know that all 5,000 health care professionals have at least a couple of narcolepsy patients under their care. And our representatives are out educating the entire 5,000 network. So I would say we continue to happen.

關於滲透率目標，我心中不一定有目標，但我確實相信這一領域仍有足夠的發展空間，或者我們知道所有 5,000 名醫療保健專業人員至少患有嗜睡症在他們照顧下的病人。我們的代表正在對整個 5,000 個網路進行教育。所以我想說我們會繼續發生。

We've seen growth from 30% to 33% to north of 35%, we're now approaching 40%. So I think there's a regular rhythm of continuing to add to this space and we're anticipating continued growth in this segment and I do believe that there's ample room to grow for unique prescribers.

我們看到成長從 30% 到 33%，再到 35% 以上，現在接近 40%。因此，我認為繼續增加這一空間的節奏是有規律的，我們預計這一領域將持續成長，我確實相信，對於獨特的處方者來說，有足夠的成長空間。

And then the second phase of that, David, is as they start their first patient on WAKIX, the next phase of growth in this audience is growing the depth of their prescribing. And we are starting to see that as well. So it's a very unique audience insulated from the oxybate both branded and generic, certainly as a catalyst for future growth moving forward.

然後第二階段，大衛，當他們開始使用 WAKIX 治療第一個患者時，該受眾的下一階段增長是增加他們處方的深度。我們也開始看到這一點。因此，這是一個非常獨特的受眾，不受品牌和仿製藥的影響，當然可以作為未來成長的催化劑。

Thank you.

謝謝。

Thanks, David.

謝謝，大衛。

Graig Suvannavejh, Mizuho Securities.

Graig Suvannavejh，瑞穗證券。

Hi, good morning. Thanks for taking my questions and congratulations also from me on the progress in the quarter. My first question is on the commercial business in WAKIX and I might have missed this detail before. But as we think about the second half in terms of net patient adds, I think that historically we've seen over the past several years, net patient adds for the second half around 600 to even 700.

嗨，早安。感謝您提出問題，並對本季的進展表示祝賀。我的第一個問題是關於 WAKIX 的商業業務，我以前可能錯過了這個細節。但當我們考慮下半年的淨患者增加量時，我認為從歷史上看，我們在過去幾年中看到，下半年的淨患者增加量約為 600 至 700 人。

And I think based on what I had heard earlier from Jeff Dierks that you would plan to end the year at 7,000. Just wanted to revisit what the second half implies if you ended at 65,50, I think by my math and again, if I have my math correct, that only implies 450 in additional net patient adds for the balance of the second half,. If you could just provide some commentary around what our expectation should be for the second half on net patient adds and appreciating that the revenue guidance has remained the same.

我認為根據我之前從 Jeff Dierks 那裡聽到的信息，你們計劃在今年年底達到 7,000 人。只是想重新審視下半場意味著什麼，如果你以 65,50 結束，我想通過我的數學，再次，如果我的數學正確，這僅意味著下半場餘額的額外淨患者增加 450。如果您能就我們對下半年淨患者增加的預期進行一些評論，並讚賞收入指導保持不變。

And the my second question, just on the HD formulation. Knowing that you're going to be testing higher doses to improve on efficacy. I'm just wondering what the expectation on safety should be. I realize you've got a GR formulation, but are you anticipating that with higher doses that you're going to be evaluating versus legacy WAKIX product that the side effect profile relatively will be the same or perhaps even less than legacy WAKIX. Any comments around what you're anticipating to see on safety relative to weight Qix with HD formulation would be appreciated. Thanks so much.

我的第二個問題是關於 HD 公式的。知道您將測試更高的劑量以提高療效。我只是想知道對安全的期望應該是什麼。我知道您有 GR 配方，但您是否預計，與傳統 WAKIX 產品相比，您要評估的劑量更高，其副作用相對將與傳統 WAKIX 相同或甚至更少。對於您期望看到的 HD 配方 Qix 相對於重量的安全性的任何評論，我們將不勝感激。非常感謝。

Yes. Thanks, Greg, for your questions. First one over to Jeff Dierks on the commercial side.

是的。謝謝格雷格提出的問題。第一個是商業方面的 Jeff Dierks。

Sure. So Greg, with respect to thinking about full year 2024 and patient adds. So yes, we did add about 250 average patients sequentially from the first quarter in the second quarter and reported approximately 6,550 average patient. We are reiterating our guidance of approximately 7,000 at the end of the year. So your math is correct.

當然。因此，格雷格（Greg）在考慮 2024 年全年時，患者補充道。所以，是的，我們確實從第一季到第二季連續增加了大約 250 名普通患者，並報告了大約 6,550 名普通患者。我們重申年底時大約 7,000 人的指引。所以你的數學是正確的。

And I think it's important that you have seen historically when you're looking at year two, year three and even year four, we're now in year five of our rare orphan commercialization, and we feel extremely confident and good about the growth we're seeing. We expect continued growth through the balance of the year, as we shared a little bit earlier, we do expect the typical summer seasonality that impacts new patient starts.

我認為重要的是，當你看到第二年、第三年甚至第四年時，你會看到歷史，我們現在正處於罕見孤兒商業化的第五年，我們對我們的成長感到非常有信心和良好。我們預計今年剩餘時間將繼續成長，正如我們之前分享的那樣，我們確實預計典型的夏季季節性因素會影響新患者的就診。

You tend to have some patients who are chronically managed, scheduling their appointments in the fourth quarter for med management. So we do anticipate strong refill behavior in the fourth quarter. Typically patients like to fill their new and refill medicines before the end of the year.

往往會有一些長期接受管理的患者，將他們的預約安排在第四季度進行藥物管理。因此，我們確實預期第四季會有強勁的補充行為。通常，患者喜歡在年底前補充新藥和補充藥物。

Insurance resets, insurance changes next year. We're seeing good underlying business fundamentals, right? We recently added the pediatric narcolepsy indication approval that's ultimately help support future growth, and we'll continue to tap into that diagnosed patient opportunity as those seasonal market dynamics allow each year.

保險重置，明年保險變動。我們看到了良好的基本業務基礎，對嗎？我們最近增加了兒科發作性睡病適應症的批准，這最終有助於支持未來的成長，並且我們將在每年季節性市場動態允許的情況下繼續利用診斷患者的機會。

But we're continued, as Sandy alluded earlier, we're confident in continued growth for the balance of the year and quarter-over-quarter growth. I think if you're looking at where we anticipate ending the year, our guidance is about 7,000 should kind of help you think about the third and fourth quarter moving forward.

但正如桑迪早些時候提到的那樣，我們對今年剩餘時間的持續成長和季度環比增長充滿信心。我認為，如果您正在考慮我們預計今年結束的情況，我們的指引約為 7,000 應該可以幫助您思考第三季和第四季的未來。

Yes. And Greg, I would say in terms of the overall benefit risk profile with regards to Pitolisant and HD and our expectation, based on what we've previously seen on dose response and other data in the pivotal program, we expect that same profile to be maintained with regards to the opportunity for improved efficacy with no change in overall safety, tolerability.

是的。格雷格，我想說的是，就 Pitolisant 和 HD 的整體效益風險狀況以及我們的預期而言，根據我們之前在關鍵計劃中看到的劑量反應和其他數據，我們預計同樣的狀況將是在總體在安全性、耐受性沒有變化的情況下提高療效的機會仍然保持不變。

And Kumar, any added color on that?

Kumar，有什麼補充嗎？

I think you covered everything. Hey, good morning, Greg. The only other thing that I would like to add is, Greg, as I mentioned earlier, we plan to accelerate this program with a different date in 2028, and we did some leading-edge work where we looked at higher doses of Pitolisant. About 18 months ago, we started this study, looked at multiple doses of Pitolisant, and studied up to 118 milligrams in the repeat dose study, and the safety and tolerability profile was very similar to the highest label dose of (inaudible) , which is 35.6 milligrams.

我想你涵蓋了一切。嘿，早上好，格雷格。我唯一想補充的是，Greg，正如我之前提到的，我們計劃在 2028 年的不同日期加速該計劃，並且我們做了一些前沿工作，研究了更高劑量的 Pitolisant。大約18 個月前，我們開始了這項研究，觀察了Pitolisant 的多個劑量，並在重複劑量研究中研究了高達118 毫克的劑量，其安全性和耐受性概況與最高標籤劑量（聽不見清）非常相似，即35.6毫克。

So we did not see any change in the safety and tolerability profile, and you mentioned about the gastro-resistant coating. Gastro-resistant coating, if anything, should actually result in a more positive patient experience

因此，我們沒有看到安全性和耐受性方面有任何變化，您提到了耐胃塗層。耐胃塗層（如果有的話）實際上應該會帶來更積極的患者體驗

David Wong, Citigroup.

大衛黃，花旗集團。

Hi, there. Good morning and thanks for taking my questions. So first one, I just wanted to ask about your level of confidence here in meeting the projected PADUPA date of 2026 and 2028 for the GR and HD formulations, respectively, and where are the key gating factors to get to in terms of data packages for filing with the agency?

你好呀。早安，感謝您提出我的問題。因此，第一個問題，我只想問一下您對 GR 和 HD 配方分別滿足 2026 年和 2028 年預計 PADUPA 日期的信心程度，以及就數據包而言，關鍵的控制因素在哪裡？ ？

And then second question, in terms of the PPM116 molecule, which you're taking forward to IND filing. Are there any features there which you believe could differentiate from other Orexin agonist that are currently in development and how do you think about developing for various narcolepsy versus IH? Thank you

第二個問題是關於 PPM116 分子，您正在將其提交 IND 申請。您認為有哪些功能可以與目前正在開發的其​​他 Orexin 激動劑區分開來？謝謝

Yes, David, good morning. Thanks for your question. With regards to on our confidence in the projects and bidding for dates for pitolisant GR and HD program. I think we are confident in terms of the development plan that's laid out and our ability to hit those things. I can ask Kumar provide further color on that and what some of the key major milestones are towards that? Kumar?

是的，大衛，早安。謝謝你的提問。關於我們對 Pitolisant GR 和 HD 項目的項目和投標日期的信心。我認為我們對制定的發展計劃以及實現這些目標的能力充滿信心。我可以請庫馬爾提供進一步的信息，以及實現這一目標的一些關鍵里程碑是什麼？庫馬爾？

Hey, good morning, David. Thanks for the question. Regarding the gastro resistant formulation, as we disclosed earlier during the call, we are on track to start (inaudible) study in the fourth quarter of this, and we will start the total bioequivalent study in the first quarter.

嘿，早上好，大衛。謝謝你的提問。關於胃耐受製劑，正如我們早些時候在電話會議中所披露的那樣，我們預計在第四季度開始（聽不清楚）研究，並且我們將在第一季開始總生物等效性研究。

And we are on track for PDUFA in 2026. We are confident about it. In terms of the HD formation, we just disclosed the initial PK data from the (inaudible) study. And I also mentioned earlier on some of the leading edge work that we have already done to accelerate this program, like establishing safety margin, we conducted a quality due the study in patients with narcolepsy who have fatigue, identify the right instrument to study fatigue in this patient population. We anticipate this to be in the next stage of the clinical development in 2025, and we will provide more color to this as we solidify some of our plans.

我們預計在 2026 年實現 PDUFA。我們對此充滿信心。就 HD 形成而言，我們剛剛揭露了（聽不清楚）研究的初始 PK 資料。我之前也提到過，我們已經為加速該計劃所做的一些前沿工作，例如建立安全裕度，我們對患有疲勞的發作性睡病患者進行了一項高品質的研究，確定了研究疲勞的正確工具這個患者群。我們預計這將在 2025 年進入臨床開發的下一階段，隨著我們鞏固一些計劃，我們將為此提供更多的色彩。

Regarding your last question about TPM1116, our Orexin (inaudible) agonist, some of the differentiating features David, are, first of all, this belongs to a novel chemical period. It has a different chemical scaffold and it's different than any other (inaudible) that we know. And what we have seen in our preclinical experiments is the most potent or in (inaudible) information that is available in the public domain on various (inaudible) products and deceptive actives.

關於你關於 TPM1116 的最後一個問題，我們的食慾素（聽不清楚）激動劑，大衛的一些區別特徵是，首先，這屬於一個新的化學時期。它具有不同的化學支架，並且與我們所知的任何其他（聽不清楚）不同。我們在臨床前實驗中看到的是公共領域中關於各種（聽不清楚）產品和欺騙性活性物質的最有效的或（聽不清楚）資訊。

The fastest this is most important potent Orexin-2 agonist does view (technical difficulty) . They are on toe for NT1, NT2 based on the information on other compounds, you may have noticed that typically NT2 required higher dose than NT1 the higher, the higher does than NT2. So from that perspective, in terms of avoiding the off-target side of that, that gives us some, and also the preclinical safety data that we have seen is actually very encouraging and definitely to believe that TPM1116 could be the potential best-in-class compound when it comes to our Orexin inceptor agonist,

這是最重要的有效 Orexin-2 激動劑所觀察到的最快速度（技術難度）。他們根據其他化合物的資訊對 NT1、NT2 保持警惕，您可能已經注意到，通常 NT2 需要的劑量比 NT1 更高，比 NT2 更高。因此，從這個角度來看，就避免脫靶而言，這給了我們一些，而且我們所看到的臨床前安全數據實際上非常令人鼓舞，並且絕對相信 TPM1116 可能是潛在的最佳-當談到我們的食慾素受體激動劑時，

Corinne Jenkins, Goldman Sachs.

科琳·詹金斯，高盛。

Hey, good morning. Maybe from suggest, you've talked about the $1 billion target for sales. I guess maybe you can just talk a little bit more about the path from here where we are today to there, particularly with respect to the patient growth you need to see to get to that target?

嘿，早安。也許根據建議，您談到了 10 億美元的銷售目標。我想也許你可以多談談從現在到那裡的路徑，特別是關於實現該目標所需的患者成長？

And then on maybe like a little bit more disclarification, can you just provide some color around growth to that through the first half of this year. I think sales are relatively flat versus second half '23. But obviously, you took price and patients have continued to grow. So curious what you're seeing there and how we should think about growth for the rest of balance of the year? Thanks.

然後，也許需要更多澄清，您能否為今年上半年的成長提供一些色彩。我認為與 23 年下半年相比，銷售額相對持平。但顯然，你接受了價格，病人就持續成長。很好奇您在那裡看到了什麼以及我們應該如何考慮今年剩餘時間的成長？謝謝。

Yes. Sure, Corinne, good morning, Jeff.

是的。當然，科琳，早安，傑夫。

Yes. So great question, Corinne. So path to $1 billion, I mean, based obviously on our net average price per patient, achieving $1 billion basically is looking, getting north of about 9,000 average patients on product. We just finished the quarter and reported approximately 6,550.

是的。這是一個很好的問題，科琳。因此，我的意思是，顯然，根據我們每位患者的淨平均價格，實現 10 億美元的目標基本上是讓產品的平均患者數量超過約 9,000 名。我們剛結束本季度，報告約為 6,550。

So our goal to achieve $1 billion is simply looking at adding another 2,500 average patients between now, mid-2024 and mid-2030. So over the next six years. And I think, obviously, based upon our four years of history and what we believe in continued growth, the path to $1 billion is very clear.

因此，我們實現 10 億美元的目標只是考慮從現在到 2024 年中期到 2030 年中期再增加 2,500 名普通患者。所以在接下來的六年裡。我認為，顯然，根據我們四年的歷史以及我們對持續成長的信念，通往 10 億美元的道路是非常明確的。

We obviously have a very good analog in the oxybate, which was able to achieve $1 billion on its path with a much smaller ability to tap into only about 4,000 health care professionals. They didn't have, obviously, the access to the full diagnosed patient opportunity. So we believe accessing 9,000 health care professionals with a goal of having to achieve another 2,500 average patients in the next six years, I think is absolutely achievable.

顯然，我們在 oxybate 中有一個非常好的類似物，它能夠在其發展道路上實現 10 億美元的收入，但能力要小得多，只能利用大約 4,000 名醫療保健專業人員。顯然，他們沒有獲得全面診斷患者的機會。因此，我們相信，在未來六年內讓 9,000 名醫療保健專業人員接觸到另外 2,500 名普通患者，我認為這是絕對可以實現的。

And that's why we look at this as a $1 billion-plus opportunity. And I think we're very excited about the ability to enhance the Pitolisant franchise by adding both GR and HD along that time period and really building out this franchise and being able to help thousands of patients living with narcolepsy.

這就是為什麼我們認為這是一個價值超過 10 億美元的機會。我認為我們非常興奮能夠透過在這段時間內添加 GR 和 HD 來增強 Pitolisant 特許經營權，並真正建立這個特許經營權並能夠幫助數千名嗜睡症患者。

Sandeep, comments on (inaudible)

桑迪普，評論（聽不清楚）

Sure. Yes. Thanks, Corinne for the question. Generally, I would say, have in line with what we've seen in the past, typically is lower in the first quarter for the year. And then as you go into the second quarter touched the (inaudible) and that's what we've seen roughly our average per patient about (inaudible) a quarter of this quarter. We took a price increase earlier this year. So I think generally, it's in line with our expectations on how the evolution and then it stabilizes and improves in the second half of the year.

當然。是的。謝謝科琳提出的問題。一般來說，我想說，與我們過去所看到的情況一致，通常在今年第一季會較低。然後，當您進入第二季度時，我們會看到（聽不清楚），這就是我們在本季度四分之一左右（聽不清楚）的每個患者的平均水平。今年早些時候，我們提高了價格。所以我認為總的來說，這符合我們對下半年如何演變以及穩定和改善的期望。

Thank you.

謝謝。

Thanks, Corinne.

謝謝，科琳娜。

Jason Gerberry, Bank of America.

傑森‧格伯里，美國銀行。

Hi, Jeff and team. This is Pavan Patel on for Jason Gerberry. The first question is that (inaudible) improved GI side effects that pitolisant and gastro-resistant has the potential to address. So given rates were only 6% in Phase 3 and presumably mitigated by titration. Is there a higher real-world dropout rate with WAKIX? And then I have a follow-up question, if I may.

嗨，傑夫和團隊。我是帕萬·帕特爾 (Pavan Patel)，代表傑森·格伯里 (Jason Gerberry)。第一個問題是（聽不清楚）改善胃腸道副作用，pitolisant 和胃抗藥性有可能解決。因此，第 3 階段的給定比率僅為 6%，並且可能透過滴定來緩解。WAKIX 在現實世界中的退出率是否更高？如果可以的話，我還有一個後續問題。

Sure. Thanks for the question. I think Kumar can address. I think it's, the Pitolisant GR, the design is it's really the predisposition. So it's not relating to the tolerability profile and the WAKIX, and the incidence of nausea.

當然。謝謝你的提問。我認為庫馬爾可以講話。我認為，Pitolisant GR 的設計就是它的真正傾向。所以它與耐受性概況和 WAKIX 以及噁心的發生率無關。

But as we said, patients with narcolepsy, the vast majority have GI symptoms related to underlying mechanism of disease. So a lot of them experience the potential for nausea, vomiting and bowel discomfort. And they see that also with other narcolepsy treatment.

但正如我們所說，發作性睡病患者絕大多數都具有與潛在疾病機制相關的胃腸道症狀。因此，他們中的許多人可能會出現噁心、嘔吐和腸道不適。他們在其他發作性睡病治療中也看到了這一點。

So the predisposition to what is likely to co-morbid symptomatology, the GR feature can potentially reduce that potential. And then especially in the HD program as we go up on the dose, that GR feature could be beneficial in that regard.

因此，對可能出現的共病症狀的傾向，GR 特徵可能會降低這種潛力。然後，特別是在 HD 程序中，當我們增加劑量時，GR 功能在這方面可能是有益的。

Kumar, additional thoughts?

庫馬爾，還有什麼想法嗎？

Good to fill, Jeff. I think, I may want to add is with the GR formulation, apart from the gastro resistant positive attribute, not just in general for patients with narcolepsy, it also enables us to start at the therapeutic dose range, I mean, as you know takes all the medications that are used by this patient requires some kind of titration.

很高興能填補，傑夫。我想，我可能想補充一點的是，GR製劑除了具有胃抵抗性積極屬性外，不僅適用於一般嗜睡病患者，它還使我們能夠從治療劑量範圍開始，我的意思是，正如你所知，該患者使用的所有藥物都需要某種滴定。

And this enables us to start at the beginning of the therapeutic dose range, so that the patients don't have to wait until they realize efficacy, the faster efficacy, better compliance and better patient experience overall.

這使得我們能夠從治療劑量範圍的開始就開始，讓患者不必等到意識到療效，整體上療效更快、依從性更好、患者體驗更好。

Thanks, Jeff. And then my second question is related to your pipeline. On EPX-100, the 5HT2 mechanism is similar to UCB's commercial stage (inaudible) and long board development stage capturing, for which the Phase 3 study is expected to start by year-end 2024.

謝謝，傑夫。我的第二個問題與你們的管道有關。在 EPX-100 上，5HT2 機制類似於 UCB 的商業階段（聽不清楚）和長板開發階段捕獲，其第 3 階段研究預計將於 2024 年底開始。

So I guess how can EPX-100 differentiate itself in the landscape? Is it efficacy or safety improvement that we're looking for in [Dravet] syndrome with the top-line data in 2026? And maybe if you can help us understand where you see this fitting into the current treatment landscape? Thank you.

那麼我想 EPX-100 如何在市場中脫穎而出？我們正在尋找 2026 年第一線資料中 [Dravet] 症候群的療效或安全性改進嗎？也許您可以幫助我們了解您認為這與當前的治療格局有何契合？謝謝。

Yeah. That's a great question. Look, as we mentioned, the teratogenic mechanism of action is the developmental epileptic encephalopathy is well established, right? And we also saw that with zebrafish model with clemizole (inaudible). And this has a pretty good predictive ability when it comes to efficacy and developmental epileptic encephalopathy.

是的。這是一個很好的問題。看，正如我們所提到的，發育性癲癇性腦病變的致畸作用機制已經很確定了，對吧？我們也透過克立咪唑的斑馬魚模型看到了這一點（聽不清楚）。在療效和發育性癲癇性腦病變方面，這具有相當好的預測能力。

The question about differentiation is a very good one. How do we differentiate? I mean as we now the drug that have currently yield in development epileptic encephalopathy (inaudible) syndrome, LGS, they have significant limitations in terms of safety and tolerability.

關於差異化的問題是一個很好的問題。我們如何區分？我的意思是，正如我們現在開發的治療癲癇性腦病（聽不清楚）綜合症（LGS）的藥物，它們在安全性和耐受性方面有很大的限制。

For example, Epygenix has significant incidence of nausea of abdominal discomfort and diarrhea up to 30% of patients and patients also need to monitor liver function tests before starting treatment and the regular intervals thereafter.

例如，Epygenix 的噁心、腹部不適和腹瀉的發生率高達 30%，患者還需要在開始治療前以及治療後定期監測肝功能檢查。

For example, you mentioned about ECC (inaudible) . Our (inaudible) programs artistically and on top of it, the patients have to get echocardiogram before starting the treatment and (technical difficulty)pulmonary artery hypertension.

例如，您提到了 ECC（聽不清楚）。我們的（聽不清楚）節目很藝術，最重要的是，患者在開始治療和（技術難度）肺動脈高壓之前必須進行超音波心動圖檢查。

What we have with EPX-100 of which by the way, we are developing a new chemical entity as requested by the FDA. The capacity of non-clinical stock studies did not show any concern about any (inaudible) issue or have (inaudible) issue and neither we did see anything we have Phase 1 has the volunteer studies as well anything of concern.

順便說一下，我們正在按照 FDA 的要求開發新的化學實體，即 EPX-100。非臨床庫存研究的能力沒有表現出對任何（聽不清楚）問題或有（聽不清楚）問題的任何擔憂，我們也沒有看到第一階段有任何志願者研究以及任何令人擔憂的事情。

So the differentiation really is safety and tolerability and in our clinical trial, we haven't seen any of those meeting tolerable issues, any laboratory abnormalities. So we believe the efficacy will be somewhere in the range that will be meaningful to the patient, but from a safety profile, it will offer a discrete safety (technical difficulty)

因此，差異實際上在於安全性和耐受性，在我們的臨床試驗中，我們沒有看到任何藥物遇到可耐受的問題，也沒有任何實驗室異常。因此，我們相信療效將在對患者有意義的範圍內，但從安全性來看，它將提供離散的安全性（技術難度）

Thank you.

謝謝。

Thank you. At this time, I show no further questions. I would like to turn the call back to Jeff Dayno for any closing remarks.

謝謝。此時，我沒有再提出任何問題。我想將電話轉回給傑夫·戴諾，讓其發表結束語。

Thank you, Todd, and thanks, everyone, for joining our call today and for your interest in Harmony. We look forward to our Investor Day on October 1 in New York City, when we'll have the opportunity to showcase and highlight the value of our late-stage pipeline as well as providing you updates later this year as we execute on our long-term growth strategy. Thank you and have a great day.

謝謝托德，謝謝大家今天加入我們的電話會議以及對 Harmony 的興趣。我們期待 10 月 1 日在紐約市舉行的投資者日，屆時我們將有機會展示和強調我們後期管道的價值，並在今年晚些時候為您提供我們長期執行的最新信息。謝謝您，祝您有美好的一天。

Thank you. This does conclude Harmony's Bioscience second-quarter 2024 financial results conference call. You may now disconnect your line and have a wonderful day.

謝謝。Harmony 的 Bioscience 2024 年第二季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。