Harmony Biosciences Holdings Inc (HRMY) 2024 Q3 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 third quarter 2024 financial results conference call. All participants have been placed on mute to prevent any background noise.

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年第三季財務業績電話會議。所有參與者均已靜音，以防止任何背景噪音。

After the speaker's remarks, there will be a question-and-answer session. (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 Investo Relations.

演講者發言後，將進行問答環節。（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關係主管布倫南·多伊爾 (Brennan Doyle)。

Thank you, operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences third quarter 2024 financial results and provide a business update.

謝謝你，接線生。大家早安，感謝您今天加入我們，我們將回顧 Harmony Biosciences 2024 年第三季的財務表現並提供業務更新。

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

在我們開始之前，我鼓勵大家造訪我們網站的投資者部分，尋找我們今天討論的資料，包括我們的 GAAP 與非 GAAP 財務指標的調整表。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 on today's call are Dr Jeffrey Dayno, President and CEO; Jeffrey Dierks, Chief Commercial Officer; Dr. Kumar Budur, Chief Medical and Scientific Officer, and Sandeep 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 Jeffrey Dayno 博士； Jeffrey Dierks，首席商務長；首席醫療和科學官庫馬爾·布杜爾 (Kumar Budur) 博士和首席財務官兼首席行政官桑迪普·卡帕迪亞 (Sandeep Kapadia)。

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

提醒一下，我們今天將根據我們當前的期望和信念發表前瞻性聲明。這些陳述存在一定的風險和不確定性。我們的實際結果可能存在重大差異，即使情況發生變化，我們也不承擔更新這些聲明的義務。我們鼓勵您查閱我們向 SEC 提交的文件中提到的風險因素，以了解更多詳細資訊。

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, Brennan, and thanks everyone for joining our conference call today. Q3 was another quarter of strong momentum for the team at Harmony, driving significant revenue growth for WAKIX and advancing our late stage clinical development programs. At our successful Investor Day event earlier this month, we were excited to share new data and outlined a clear path to becoming the leading CNS company focused on developing and delivering innovative treatments to patients with unmet medical needs.

謝謝布倫南，也謝謝大家今天參加我們的電話會議。第三季度是 Harmony 團隊又一個強勁勢頭的季度，推動了 WAKIX 營收的顯著成長，並推進了我們的後期臨床開發專案。在本月稍早成功舉辦的投資者日活動中，我們很高興分享新數據，並概述了成為領先的中樞神經系統公司的清晰路徑，專注於為醫療需求未得到滿足的患者開發和提供創新治療方法。

As we shared during that presentation, our robust late stage pipeline is poised to deliver one or more new product or indication launches each year over the next five years. With each catalyst, we are delivering on our promise to patients and generating long term durable value creation for shareholders. In fact, with this team in Harmony that has driven our success thus far, our current pipeline is successful, is poised to deliver over $3 billion in net revenue going forward.

正如我們在演講中分享的那樣，我們強大的後期管道準備在未來五年內每年推出一種或多種新產品或適應症。透過每一個催化劑，我們都在兌現對病人的承諾，並為股東創造長期持久的價值。事實上，Harmony 的這個團隊迄今為止推動了我們的成功，我們目前的管道是成功的，未來有望實現超過 30 億美元的淨收入。

Also, during our Investor Day, I highlighted what we believe to be one of the strongest and most promising pipelines in the industry for people living with rare neurological diseases. Our pipeline now includes three orphan rare CNS franchises, each with peak sales potential of $1 billion to $2 billion, 8 assets across 13 development programs with three of them in pivotal phase three trials and a fourth to initiate before year end.

此外，在我們的投資者日期間，我強調了我們認為對於患有罕見神經系統疾病的人來說，該行業最強大和最有前途的管道之一。我們的管道現在包括三個孤兒稀有中樞神經系統特許經營權，每個資產的峰值銷售潛力為10 億至20 億美元，涵蓋13 個開發項目的8 項資產，其中三個處於關鍵的第三階段試驗，第四個將在年底前啟動。

Given the tremendous growth in our pipeline, we will not be able to go into depth on all the development programs on this call. But the key points that I want you to take away from our call today regarding our robust pipeline are these: first, we continue to strengthen our leadership position in sleep/wake; we are preparing to submit our sNDA, pitolisant, in idiopathic hypersomnia or IH.

鑑於我們的管道的巨大增長，我們將無法在這次電話會議上深入探討所有開發計劃。但我希望大家從今天的電話會議中了解到我們強大的產品線的關鍵點是：首先，我們繼續加強我們在睡眠/覺醒領域的領導地位；我們正在準備提交用於治療特發性嗜睡症或 IH 的 sNDA。

We are advancing the pitolisant next-gen programs and we are on track to submit an IND for our potential best-in-class orexin-2 agonist in mid 2025 and then enter the clinic the second half of next year.

我們正在推進pitolisant下一代項目，我們預計在2025年中期提交我們潛在的同類最佳orexin-2激動劑的IND，然後在明年下半年進入臨床。

Second, with EPX-100, or Clemizole Hydrochloride, we have the most advanced and promising late stage development program in the class of five HT two receptor agonists to address the serious unmet medical need for the rare childhood onset epilepsies known as developmental epileptic encephalopathies or DEEs. EPX-100 is in an ongoing phase III registrational trial for patients with Dravet syndrome and on track for topline data in 2026. And we will be initiating a pivotal phase three trial for EPX-100 in patients with Lenox-Gastaut syndrome before year end.

其次，透過EPX-100（或鹽酸克立咪唑），我們擁有五種HT2 受體激動劑類別中最先進、最有前途的後期開發計劃，以解決罕見的兒童期癲癇（稱為發育性癲癇性腦病變或發育性癲癇性腦病變）的嚴重未滿足的醫療需求。EPX-100 正在進行針對 Dravet 症候群患者的 III 期註冊試驗，預計在 2026 年獲得第一線數據。我們將在年底前針對 Lenox-Gastaut 症候群患者啟動一項針對 EPX-100 的關鍵三期試驗。

In addition, we have another asset in our epilepsy pipeline, EPX-200 or Lorcaserin in a liquid formulation, which is a selective 5HT2C receptor agonist. And both of these have significant upside potential as the market has recently acknowledged with the acquisition of a 5HT2C agonist asset that just recently initiated a phase three trial in Dravet' syndrome.

此外，我們的癲癇產品管線中還有另一種資產，液體製劑中的 EPX-200 或 Lorcaserin，它是一種選擇性 5HT2C 受體激動劑。這兩種藥物都具有巨大的上升潛力，因為市場最近承認了對 5HT2C 激動劑資產的收購，該資產最近剛啟動了 Dravet 症候群的第三階段試驗。

Third, there are exciting near-term catalysts coming in the first half of next year, including FDA's decision on file acceptance of our IH sNDA submission going in later this year, as well as topline data for ZYN-002 from the pivotal phase three RECONNECT trial in patients with Fragile X syndrome. If these data are positive, it could put us on a path toward bringing the first approved treatment to the market for patients living with Fragile X syndrome.

第三，明年上半年將出現令人興奮的近期催化劑，包括 FDA 決定接受我們今年稍後提交的 IH sNDA 提交文件，以及來自關鍵第三階段 RECONNECT 的 ZYN-002 的主要數據脆性X 綜合徵患者的試驗。如果這些數據是正面的，它可能會讓我們走上一條道路，將第一個批准的治療方法推向市場，治療脆性 X 症候群患者。

I want to share some highlights with you on our development programs and then Kumar will expand on these key points later in the call. First, on the strengthening of our leadership in sleep/wake, which is the foundation of our business, we shared new data at our Investor Day from the long term extension trial of Pupitolisant in patients with IH. These data demonstrated robust efficacy and sustained response out beyond one year.

我想與您分享我們發展計劃的一些要點，然後庫馬爾將在稍後的電話會議中詳細闡述這些要點。首先，為了加強我們在睡眠/覺醒領域的領導地位（這是我們業務的基礎），我們在投資者日分享了 Pupitolisant 在 IH 患者中進行長期擴展試驗的新數據。這些數據證明了一年以上的強大功效和持續反應。

As Kumar will show you, the majority of patients were maintained within the normal range on the Epworth Sleepiness scale for over one year after coming into the trial at a moderate or severe level of sleepiness. This, along with real world evidence and a strong overall benefit risk proposition for pitolisant, is the reason for our strong conviction in pursuing an IH indication for pitolisant and we are on track to submit an sNDA before year end.

正如庫馬爾將向您展示的那樣，大多數患者在進入試驗後一年多的時間裡都保持在中度或重度嗜睡水平的 Epworth 嗜睡量表的正常範圍內。這一點，加上現實世界的證據和對pitolisant強有力的整體效益風險主張，是我們堅定追求pitolisant IH適應症的原因，我們預計在年底前提交一份sNDA。

Building off of the innovation of the first in class molecule in pitolisant with its novel mechanism of action and the success of WAKIX in the market is our next gen formulations of pitolisant. Both of these programs, pitolisant gastro resistant or GR and pitolisant high dose or HD reflect patient centric drug development with the goal to make -- to take a good drug and make it even better by addressing ongoing unmet medical needs in patients with narcolepsy.

我們的下一代 Pitolisant 配方以 Pitolisant 同類首個分子的創新及其新穎的作用機制和 WAKIX 在市場上的成功為基礎。這兩個項目，pitolisant胃抗性或GR和pitolisant高劑量或HD反映了以患者為中心的藥物開發，其目標是——服用一種好藥，並通過解決發作性睡病患者持續未得到滿足的醫療需求來使其變得更好。

Pitolisant GR is on track for PDUFA in 2026 and Pitolisant HD is on track for PDUFA in 2028 and Jeff Dierks provide more color on the strategy behind those programs and how our unique commercial model positions us to optimize the opportunity to both grow and extend the pitolisant franchise into the 2040s.

Pitolisant GR 預計在 2026 年實現 PDUFA，Pitolisant HD 預計在 2028 年實現 PDUFA，Jeff Dierks 提供了更多關於這些計劃背後的策略的信息，以及我們獨特的商業模式如何使我們能夠優化成長和擴展 Pitolisant 的機會特許經營權進入2040年代。

The next wave of innovation for the treatment of narcolepsy and other central disorders of hypersomnolence are the orexin-2 receptor agonist. As leaders in sleep/wake, we have followed this space closely over the past few years, diligence -- several of the orexin-2 agonist programs. And then earlier this year, licensing in BP1.15205 with our partner, Bioprojet, which we feel could be a potential best-in-class orexin-2 agonist compound.

治療發作性睡病和其他中樞性嗜睡症的下一波創新浪潮是 orexin-2 受體激動劑。作為睡眠/清醒領域的領導者，我們在過去幾年中密切關注著這個領域，勤勉地開展了幾個 orexin-2 激動劑項目。今年早些時候，我們與合作夥伴 Bioprojet 獲得了 BP1.15205 的許可，我們認為它可能是潛在的同類最佳 orexin-2 激動劑化合物。

This is based on several unique features of this compound. Some of which we share during our Investor Day and Kumar will review them with you later in the call. We are on track to filing an IND mid 2025 and then initiating first in-human studies in the second half of 2025.

這是基於該化合物的幾個獨特特徵。我們在投資者日期間分享了其中一些內容，庫馬爾將在稍後的電話會議中與您一起回顧。我們預計在 2025 年中期提交 IND，然後在 2025 年下半年啟動首次人體研究。

Next, I would like to take a few moments to discuss and share our excitement with you regarding our rare epilepsy franchise that we recently brought in house through the acquisition of Epygenix Therapeutics.

接下來，我想花一些時間與您討論並分享我們對我們最近透過收購 Epygenix Therapeutics 引入的罕見癲癇專營權的興奮之情。

This is relevant particularly in light of some of the recent developments in the competitive landscape which point to the significant value of new treatments for developmental epileptic encephalopathies.

鑑於競爭格局的一些最新發展表明了發展性癲癇性腦病新療法的重要價值，這一點尤其重要。

Many of the currently approved therapies face limitations in terms of efficacy, safety and/or tolerability, leaving a treatment gap and serious unmet medical need that must be addressed for patients living with these rare and refractory seizure disorders and their caregivers.

目前批准的許多療法在療效、安全性和/或耐受性方面都面臨局限性，留下了治療缺口和嚴重未滿足的醫療需求，必須為患有這些罕見和難治性癲癇病的患者及其護理人員解決這些需求。

We view the recent interest in this space as validation of our approach and Harmony is again, proud to be at the forefront of innovation. To put it simply, this space involves compounds that act at the serotonin or 5HT type 2 receptor and enhance serotonergic tone in the brain.

我們認為最近對該領域的興趣是對我們方法的驗證，Harmony 再次自豪地處於創新的前沿。簡而言之，這個空間涉及作用於血清素或 5HT 2 型受體並增強大腦中血清素能張力的化合物。

We have two investigational products for DEEs, EPX-100 or clemizole hydrochloride and EPX-200, a liquid formulation of Lorcaserin. Kumar will share with you more details regarding these compounds and their development programs, but what I want to highlight for you is the following.

我們有兩種用於 DEE 的研究產品：EPX-100 或鹽酸克立咪唑和 EPX-200（一種氯卡色林液體製劑）。庫馬爾將與您分享有關這些化合物及其開發計劃的更多詳細信息，但我想向您強調以下內容。

The mechanism of action for both, EPX-100 and EPX-200, working through 5HT2 receptors and serotonin modulation has been validated in the zebrafish model developed by Scott Baraban who shared his work at our Investor Day, which demonstrated 100% predictability, both 100% positive and 100% negative predictability on efficacy for compounds that were screened in his zebra fish model.

EPX-100 和EPX-200 透過5HT2 受體和血清素調節發揮作用的機制已在Scott Baraban 開發的斑馬魚模型中得到驗證，他在我們的投資者日分享了他的工作，該模型證明了100 % 的可預測性，兩者都是100在他的斑馬魚模型中篩選的化合物功效的 % 陽性和 100% 陰性可預測性。

We have the most advanced clinical development program of the 5HT2 agonist compounds with EPX-100 in an ongoing registrational trial for patients with Dravet syndrome, which is on track for topline data in 2026, as well as a pivotal phase three trial for patients with Lenox-Gastaut syndrome, which is on track to initiate before year end.

我們擁有最先進的5HT2 激動劑化合物與EPX-100 的臨床開發計劃，該計劃正在進行一項針對Dravet 綜合徵患者的註冊試驗，該試驗預計將在2026 年獲得頂線數據，此外還有一項針對Lenox患者的關鍵三期試驗-加斯托綜合症，預計在年底前出現。

What I want you to take away is that we believe that we have the most robust, most promising and advanced portfolio of assets in the clinic for patients with DEEs and are confident that if successful, our portfolio can offer new treatment options for patients and drive significant value creation for our shareholders.

我想讓您了解到的是，我們相信我們在臨床上為DEE 患者擁有最強大、最有前途和最先進的資產組合，並且相信如果成功，我們的資產組合可以為患者提供新的治療選擇，並推動為我們的股東創造重大價值。

Lastly, on our pipeline, as you can see, we have strategically expanded our pipeline and diversified our portfolio across three orphan rare CNS franchises and built what we believe is one of the most exciting and promising pipelines in the industry for patients living with rare neurological diseases.

最後，在我們的產品線中，正如您所看到的，我們策略性地擴展了我們的產品線，並在三個孤兒罕見中樞神經系統專營權中實現了產品組合的多元化，並為患有罕見神經系統疾病的患者建立了我們認為是該行業中最令人興奮和最有前途的產品線之一疾病。

Importantly, I want to make sure that our near-term catalysts coming in the first half of next year are top of mind for investors. These include FDA decision on file acceptance for our IH sNDA submission in the first quarter next year, followed by the highly anticipated topline data readout of the pivotal phase 3 RECONNECT study of ZYN-002 in patients with Fragile X syndrome which is on track for readout midyear. These are exciting catalysts as we continue to advance our pipeline and build long term value creation.

重要的是，我想確保明年上半年出現的近期催化劑是投資者的首要考慮因素。其中包括FDA 在明年第一季決定接受我們的IH sNDA 提交文件，隨後是ZYN-002 在脆性X 綜合徵患者中進行的關鍵3 期RECONNECT 研究備受期待的頂線數據讀出，該研究即將讀出年中。當我們繼續推進我們的產品線並建立長期價值創造時，這些都是令人興奮的催化劑。

Switching gears, while we advance our late-stage development programs, we remain focused on execution across the company and delivered another solid quarter with WAKIX net revenue of $186 million. This enabled Harmony to surpass $2 billion in cumulative net revenue for WAKIX generated in less than five years on the market, which is a significant accomplishment. With these strong results, we are once again reiterating our 2024 net revenue guidance of $700 million to $720 million and remain confident in WAKIX being a $1 billion-plus market opportunity in narcolepsy alone and we are well on our way to achieving that.

換個角度，在我們推進後期開發計劃的同時，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 1.86 億美元。這使得 Harmony 在上市不到五年的時間內為 WAKIX 帶來了超過 20 億美元的累積淨收入，這是一項重大成就。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，並對 WAKIX 僅在嗜睡症領域就擁有超過 10 億美元的市場機會充滿信心，我們正在努力實現這一目標。

We remain active in business development with a dedicated team that has deep experience and the goal is to expand our pipeline even further. With approximately $505 million in cash, cash equivalents and investments as of September 30, we are in a strong financial position to execute on additional business development opportunities. And if we do so, we'll apply the same strategic and thoughtful approach that we have demonstrated thus far.

我們擁有一支經驗豐富的敬業團隊，並持續積極開展業務發展，目標是進一步擴大我們的產品線。截至 9 月 30 日，我們擁有約 5.05 億美元的現金、現金等價物和投資，我們的財務狀況良好，可以抓住更多的業務發展機會。如果我們這樣做，我們將採用迄今為止所展示的相同的策略和深思熟慮的方法。

This is all to say that Harmony continues to be a growth story. And while I am proud of what we have built at Harmony in just our first seven years, we are just getting started. We have this outlook because we know that when we deliver on our promise to patients by developing and delivering innovative treatments to patients living with rare neurological diseases, we generate durable, long term value creation for our shareholders.

這一切都說明 Harmony 仍然是一個成長故事。雖然我對 Harmony 在最初七年所取得的成就感到自豪，但我們才剛開始。我們之所以有這樣的前景，是因為我們知道，當我們透過為患有罕見神經系統疾病的患者開發和提供創新療法來兌現對患者的承諾時，我們就會為股東創造持久、長期的價值。

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

現在，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 quarter of continued momentum and strength in our underlying business fundamentals for WAKIX in the third quarter. Net sales for the quarter were $186 million. And with these quarterly sales, WAKIX surpassed $2 billion in cumulative net sales since launch. The solid net sales performance in the third quarter reaffirms our confidence in our net sales guidance of $700 million to $720 million for the full year 2024 and WAKIX $1 billion-plus potential in adult narcolepsy alone.

謝謝，傑夫。第三季度，我們看到 WAKIX 的基本業務基本面又呈現一個季度的持續成長動能與實力。該季度淨銷售額為 1.86 億美元。透過這些季度銷售額，WAKIX 自推出以來累計淨銷售額超過 20 億美元。第三季穩健的淨銷售額表現再次證實了我們對 2024 年全年 7 億至 7.2 億美元淨銷售額指引以及 WAKIX 僅在成人嗜睡症領域就超過 10 億美元潛力的信心。

We saw continued growth in the average number of patients on WAKIX and in the WAKIX prescriber base, both facilitated by favorable market access as seen on slide 6 and 7. The average number of patients on wake increased to approximately 6,800 in the third quarter. We're extremely pleased with the approximately 250 sequential increase in average patients on WAKIX from what we reported last quarter.

我們看到 WAKIX 的平均病患數量和 WAKIX 處方者群體持續成長，這都得益於有利的市場准入（如幻燈片 6 和 7 所示）。第三季度，平均守夜患者人數增加至約 6,800 人。我們對 WAKIX 上的平均病患數量比我們上季報告的數量連續增加約 250 名感到非常滿意。

We saw contributions from the pediatric narcolepsy indication launch in our growth in Q3, but the vast majority of our growth in the third quarter was attributed to the continued expansion in our adult narcolepsy patient base, given the larger diagnosed patient opportunity. We are extremely pleased with our launch in pediatric narcolepsy. In the first quarter since the FDA approval, we've seen strong interest from the health care, professional and patient community in the unique product profile of WAKIX as the only nonscheduled treatment option and strong payer coverage to facilitate pediatric narcolepsy patients getting on product.

我們看到兒科發作性睡病適應症的推出對我們第三季度的增長做出了貢獻，但第三季度的增長絕大多數歸因於成人發作性睡病患者群體的持續擴大，因為診斷患者的機會更大。我們對小兒發作性睡病的推出感到非常高興。自FDA 批准以來的第一季度，我們看到醫療保健、專業人士和患者群體對WAKIX 獨特的產品概況產生了濃厚的興趣，WAKIX 是唯一的非定期治療選擇，並且支付者覆蓋範圍廣泛，以促進兒科發作性睡病患者使用本產品。

The growth in average patients in the third quarter was in line with our expectations and reaffirms our confidence and our guidance of approximately 7,000 average patients by the end of the year. We saw growth in the wake prescriber base in the third quarter as well. We saw solid growth in the WAKIX prescriber base beyond the oxybates REMS enrolled healthcare professionals, demonstrating that WAKIX continues to expand the branded writer segment of the market beyond the oxybates.

第三季平均患者數量的增長符合我們的預期，並重申了我們對到年底平均患者數量約為 7,000 名的信心和指導。我們在第三季也看到了喚醒處方者基礎的成長。我們看到，除了 oxybates REMS 註冊的醫療保健專業人員之外，WAKIX 處方者群體也實現了穩健增長，這表明 WAKIX 繼續將品牌處方者市場擴展到 oxybates 之外。

We are now more than 40% penetrated in this segment of approximately 5,000 healthcare professionals at the end of the third quarter. And this segment of healthcare professionals continues to represent an insulated and durable opportunity for growth from the oxybates that we continue to tap into each quarter to drive performance.

截至第三季末，我們在這擁有約 5,000 名醫療保健專業人員的細分市場中的滲透率超過 40%。這部分醫療保健專業人員繼續代表著一個與氧酸鹽隔離且持久的成長機會，我們每季都會繼續利用它來推動業績。

Coupled with the growth we're seeing beyond the oxybate REMS enrolled healthcare professionals, we continue to see utilization of WAKIX among the approximately 4,000 oxybates REMS enrolled healthcare professionals, even with the availability of new and generic oxybate options. We're highly penetrated within this prescriber audience and see WAKIX being prescribed to additional narcolepsy patients each quarter in this segment.

再加上我們看到的 oxybate REMS 註冊醫療保健專業人員之外的增長，我們繼續看到大約 4,000 名 oxybate REMS 註冊醫療保健專業人員中使用 WAKIX，即使有新的和通用的 oxybate 選項可用。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。

WAKIX provides a meaningfully differentiated product profile and one that offers broad clinical utility across the entire narcolepsy, treating healthcare professional universe, allowing us to tap into the full diagnosed narcolepsy patient opportunity of approximately 80,000 patients, giving us confidence in future growth for WAKIX.

WAKIX 提供了一種有意義的差異化產品概況，並且在整個發作性睡病、治療醫療保健專業領域提供廣泛的臨床實用性，使我們能夠利用約80,000 名患者的全面診斷發作性睡病患者的機會，讓我們對WAKIX 的未來成長充滿信心。

Now, with WAKIX on track to achieve $1 billion-plus in narcolepsy alone, along with a strong commercial team and commercial model that we shared at our Investor day on October 1, we're making good progress on our life cycle management plan with the new formulations of the pitolisant. We're developing two new formulations of pitolisant, pitolisant GR and pitolisant HD, in a meaningful patient focused way built around unmet needs to drive incremental benefits for patients.

現在，WAKIX 僅在嗜睡症領域就有望實現超過10 億美元的目標，再加上我們在10 月1 日投資者日分享的強大商業團隊和商業模式，我們在生命週期管理計劃方面取得了良好進展，皮托利桑的新配方。我們正在開發兩種新的pitolisant配方：pitolisant GR和pitolisant HD，以一種有意義的以患者為中心的方式，圍繞未滿足的需求，為患者帶來增量利益。

Both products offer new features and attributes to address existing patient unmet needs, are on target for PDUFA dates prior to WAKIX LOE, GR in 2026 and HD in 2028, and each has provisional patents filed out to 2044 to grow and expand the pitolisant franchise.

這兩種產品都提供了新的功能和屬性，以滿足現有患者未滿足的需求，其PDUFA 日期預計早於WAKIX LOE、2026 年GR 和2028 年HD，並且每種產品都已申請到2044 年的臨時專利，以發展和擴大Pitolisant 特許經營權。

Pitolisant GR is a quick to market bioequivalents pathway with the additional benefits of a gastro resistant coating. As we know that the 90% of narcolepsy patients have GI disturbances due to their underlying disease and eliminates a titration dose, as all narcolepsy products have titration schedules and some patients cannot and do not get a therapeutic dose to achieve clinical benefits, both allowing patients to start a therapeutic dose and the potential to achieve clinical benefits sooner.

Pitolisant GR 是一種快速上市的生物等效物途徑，具有耐胃塗層的額外優點。我們知道，90％的發作性睡病患者由於其潛在疾病而患有胃腸道紊亂，並且消除了滴定劑量，因為所有發作性睡病產品都有滴定時間表，並且一些患者不能也沒有獲得治療劑量來實現臨床獲益，這兩種情況都允許患者開始治療劑量並有可能更快地實現臨床益處。

The strategy for GR is to expand the pitolisant patient base through new patient growth and using our unique commercial model, activate previous WAKIX patients who have discontinued due to either GI side effects or did not achieve a clinical benefit.

GR 的策略是透過新患者的成長來擴大 Pitolisant 患者基礎，並使用我們獨特的商業模式，激活先前因胃腸道副作用而停藥或未獲得臨床益處的 WAKIX 患者。

We see GR representing a potential $300 million to $500 million in incremental peak net sales to WAKIX. The pitolisant HD is an enhanced formulation of pitolisant with even more meaningful features to address untreated fatigue in narcolepsy, up to 60% of narcolepsy patients suffer from fatigue, and address the largest pressing need in the narcolepsy market, which is the need for enhanced efficacy.

我們認為 GR 代表 WAKIX 的淨銷售額高峰增量可能達到 3 億至 5 億美元。pitolisant HD是pitolisant的增強製劑，具有更有意義的功能，可解決發作性睡病中未經治療的疲勞問題，高達60%的發作性睡病患者患有疲勞，並解決發作性睡病市場最大的迫切需求，即增強療效的需要。

The HD development program is designed to deliver a higher dose up to two times out of WAKIX with an optimized PK profile to drive greater efficacy in EDS and cataplexy, targeting a unique indication of fatigue and narcolepsy with a gastro resistant coating and no titration at the start of the therapeutic dose.

HD 開發計畫旨在提供WAKIX 兩倍的更高劑量，並具有優化的PK 曲線，以提高EDS 和猝倒症的療效，針對疲勞和發作性睡病的獨特適應症，採用耐胃塗層且無需滴定治療劑量的開始。

The strategy for HD is to grow the pitolisant patient base through new patients, current WAKIX patients and previous WAKIX patients due to our unique commercial model and extend the durable patient revenue growth out to the mid 2040s.

HD 的策略是透過新患者、目前 WAKIX 患者和以前的 WAKIX 患者，透過我們獨特的商業模式來擴大 Pitolisant 患者基礎，並將持久的患者收入增長延長至 2040 年代中期。

We see potential peak net sales for HD of more than a $1 billion-plus in narcolepsy alone and an even larger peak opportunity with other indications being pursued in idiopathic hypersomnia and myotonic dystrophy.

我們預計 HD 治療嗜睡症的潛在淨銷售額將超過 10 億美元以上，並且在特發性嗜睡症和強直性肌肉營養不良症領域尋求其他適應症的峰值機會甚至更大。

Preliminary market research with healthcare professionals and payers on the HD target product profile showed healthcare professionals see HD as a superior product profile, given the greater efficacy addressing the most pressing need in the market and the unique fatigue indication broadens its expected use. Healthcare professionals saw broad utility for HD and expected to transition the majority of current WAKIX patients reengage previous wake patients and offer the product to all new patients.

與醫療保健專業人員和付款人對HD 目標產品概況進行的初步市場研究表明，醫療保健專業人員認為HD 是一種優越的產品概況，因為它具有更大的功效，可以滿足市場上最緊迫的需求，並且獨特的疲勞指示擴大了其預期用途。醫療保健專業人士看到了 HD 的廣泛用途，並期望將大多數現有 WAKIX 患者重新吸引到以前的喚醒患者，並向所有新患者提供該產品。

Payers also saw value in the HD profile, both pre and post WAKIX LOE and expect that favorable access for the vast majority of patients to HD without stepping through a generic pitolisant post WAKIX LOE. The pitolisant franchise strengthens our leadership position in sleep/week and is poised to deliver durable patient growth and significant revenues into the mid 2040s.

付款人還看到了 WAKIX LOE 之前和之後的 HD 資料的價值，並期望絕大多數患者能夠順利獲得 HD，而無需在 WAKIX LOE 後使用通用的 Pitolisant。Pitolisant 特許經營權鞏固了我們在每週睡眠方面的領導地位，並準備在 2040 年代中期實現患者的持久增長和可觀的收入。

So in summary, we're building an exciting sleep/wake franchise. We had another strong quarter of durable growth and performance in net sales, patient add and growth in prescribers of WAKIX.

總而言之，我們正在打造令人興奮的睡眠/喚醒系列產品。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。

Heading into the fourth quarter, we're confident in our full year guidance, our path towards $1 billion-plus in net sales and our ability to continue to help patients living with narcolepsy.

進入第四季度，我們對全年指引、淨銷售額超過 10 億美元的道路以及繼續幫助發作性睡病患者的能力充滿信心。

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

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

Thank you, Jeff. Good day, everyone and thank you for joining us today. In R&D, we continue to make great progress in advancing our pipeline program. As was clearly mentioned, we now have 13 development programs across 8 assets and the three franchises focused on rare neurological indication with high unmet medical need.

謝謝你，傑夫。大家好，感謝您今天加入我們。在研發方面，我們在推動管道計畫方面持續取得巨大進展。正如明確提到的，我們現在擁有涵蓋 8 個資產的 13 個開發項目，以及三個專營權，專注於醫療需求未滿足的罕見神經系統適應症。

We will have four phase three registration studies ongoing in four distinct indications by the end of this year with the potential to deliver one or more new products or new indication launches each year for the next five years.

今年底，我們將針對四種不同的適應症進行四項第三階段註冊研究，有可能在未來五年內每年推出一種或多種新產品或推出新適應症。

Our clinical development pipeline is shown on slide number 10 and the clinical development highlights are on slide 11 to slide 17.

我們的臨床開發流程顯示在投影片 10 上，臨床開發亮點顯示在投影片 11 至投影片 17 上。

Starting with our sleep/wake franchise. We are on track to submit an sNDA for idiopathic hypersomnia by the end of this year. Our submission will be based on the robust data from the safe three registration intu study and several lines of additional evidence that consistency support the efficacy of pitolisant in patients with idiopathic hypersomnia.

從我們的睡眠/喚醒系列開始。我們預計在今年年底前提交針對特發性嗜睡症的 sNDA。我們的提交將基於來自安全三註冊 intu 研究的可靠數據以及一系列其他證據，這些證據的一致性支持 pitolisant 對特發性嗜睡症患者的療效。

At our Investor Day on October 1, we reported new data that showed strong and sustained efficacy of pitolisant in patients with idiopathic hypotonia more than one year out in the long term extension study.

在 10 月 1 日的投資者日上，我們報告了新數據，顯示在長期擴展研究中，一年多後，pitolisant 對特發性肌張力低下患者俱有強大且持續的療效。

The mean implementing sleepiness scale was approximately nine points from baseline or beyond one year with the majority of patients in the normal range as measured by EFS score. We saw similar strong and sustained maintenance of efficacy and idiopathic hypersonic his care and sleep inertia questionnaires in the long term extension study.

實施嗜睡量表的平均數與基線相比約為 9 分或超過一年，大多數患者透過 EFS 評分測量為正常範圍。在長期擴展研究中，我們看到了類似的強而持續的療效維持和特發性高超音波速護理和睡眠慣性問卷。

In addition, we also shared the data from a large clinic in Europe in over 60 patients with IH. Data from this independent study shows that over 50% of patients with IH got better with pitolisant and approximately 40% of these patients benefited and remained stable with pitolisant monotherapy.

此外，我們也分享了歐洲一家大型診所60多名IH患者的數據。這項獨立研究的數據顯示，超過 50% 的 IH 患者在使用 Pitolisant 後病情有所好轉，其中約 40% 的患者在 Pitolisant 單一療法中受益並保持穩定。

Similar difficulty was also observed in Bioprojet [compac] use program for patients with IH. The totality of data for efficacy alongside the established safety profile of pitolisant, a nonscheduled drug, with simple dosing regimen offers a unique benefit of proposition for patients with IH, a condition with only one approved treatment that has triple affected syndrome with a challenging nighttime dosing regimen and the widespread off label use of controlled stimulant which are associated with significant safety issues. Pitolisant has the potential to address a high unmet need with very favorable benefit risk profile.

在 IH 患者的 Bioprojet [compac] 使用計劃中也觀察到類似的困難。皮托利桑（一種非定期藥物）的整體療效數據以及既定的安全性特徵和簡單的給藥方案為IH 患者提供了獨特的益處，IH 是一種只有一種批准的治療方法的疾病，具有三重影響綜合徵，且夜間給藥具有挑戰性養生法和廣泛使用受控興奮劑，這些都與重大安全問題有關。Pitolisant 有潛力以非常有利的效益風險狀況來解決高度未滿足的需求。

Moving on to next-gen pitolisant formulation, pitolisant GR and pitolisant HD. Jeff Dierk described the unique value proposition each of these formulations are expected to deliver. With pitolisant GR program, we are on track to initiate the pivotal bioequivalence study and the dosing optimization study in the first quarter of 2025 with PDUFA date in 2026.

接下來是下一代pitolisant配方，pitolisant GR和pitolisant HD。Jeff Dierk 描述了每個配方預期提供的獨特價值主張。透過pitolisant GR項目，我們預計在2025年第一季啟動關鍵生物等效性研究和劑量優化研究，PDUFA日期為2026年。

With pitolisant HD, as was indicated earlier this month, we shared preliminary data establishing pitolisant safety up to five times the current highest level to WAKIX thereby establishing safety margins for pitolisant development program.

正如本月早些時候所指出的，對於pitolisant HD，我們與WAKIX分享了初步數據，確定pitolisant安全性高達當前最高水平的五倍，從而為pitolisant開發計劃建立了安全裕度。

We are currently working on further optimizing the formulation and IND related activities and we are on track to initiate the pitolisant safety registration study in narcolepsy in the second half of 2025 with a target PDUFA in 2028. Provisional patents have been submitted for both pitolisant GR and pitolisant HD with a potential patent protection until 2044.

我們目前正在努力進一步優化配方和 IND 相關活動，我們預計將在 2025 年下半年啟動用於發作性睡病的 Pitolisant 安全註冊研究，目標是 2028 年 PDUFA。pitolisant GR 和pitolisant HD 均已提交臨時專利，潛在專利保護期至 2044 年。

Moving on to our Orexin-2 receptor agonist program, BP1.15205, formerly known as PPM1116. The in-vitro pharmacology data demonstrated a potency that is much greater compared to all publicly disclosed data on orexin-2 agonist. As you know, we did talk of compounds, potency is the most important parameter that give us the ability and the dosing flexibility to target all central disorders of hypersomnolence and potentially other disorders based on the (inaudible).

接下來是我們的 Orexin-2 受體激動劑計畫 BP1.15205，以前稱為 PPM1116。體外藥理學數據表明，與所有公開披露的 orexin-2 激動劑數據相比，其效力要大得多。如您所知，我們確實談到了化合物，效力是最重要的參數，它使我們有能力和劑量靈活性來針對所有中樞性嗜睡症和基於藥物的其他潛在疾病。（聽不清楚）。

The potency was consistent across this year and accounts are demonstrated an excellent selectivity of greater than 600 fold for a orexin-1 receptor. This translates to over 100-fold margin at orexin-1 receptor at the anticipated maximum human dose.

今年的效力一直保持一致，並證明對 orexin-1 受體具有超過 600 倍的出色選擇性。這意味著在預期的最大人體劑量下，orexin-1 受體的裕度超過 100 倍。

In addition, it also demonstrated over 1,000 fold selectivity over 150 other targets of interest and has a potential for once a day dosing. BP1.15205, with its novel chemical structure, highest potency, excellent connectivity, potential for once a day dosing and a robust preclinical data, has the potential to be the best-in-class orexin-2 receptor agonist. We are on track towards filing an IND in mid-2025 and initiating first-in-human studies in the second half of 2025.

此外，它還對 150 個其他感興趣的目標表現出超過 1,000 倍的選擇性，並且有可能每天給藥一次。BP1.15205 具有新穎的化學結構、最高的效力、出色的連接性、每日一次給藥的潛力和可靠的臨床前數據，有可能成為同類最佳的 orexin-2 受體激動劑。我們預計在 2025 年中期提交 IND，並在 2025 年下半年啟動首次人體研究。

Today, we are very excited to highlight our epilepsy franchise. And as Jeff mentioned earlier in the presentation, having the most advanced development program in DEE. We have 2 investigational candidates, EPX-100 and EPX-200 for the treatment of developmental epileptic encephalopathy.

今天，我們非常高興地重點介紹我們的癲癇專營權。正如 Jeff 在演講中前面提到的，擁有 DEE 中最先進的開發程式。我們有 2 個在研候選藥物：EPX-100 和 EPX-200，用於治療發育性癲癇性腦病變。

EPX-100 or Clemizole Hydrochloride, towards near moderation of serotonin, that is [582] and enhance (inaudible), the serotonergic mechanism of action is a validated and well-known mechanism of action in developmental epileptic encephalopathy. EPX-100 shows efficacy in the zebrafish model that has 100% positive and 100% negative predictive value.

EPX-100 或鹽酸克立咪唑，接近調節血清素，即 [582] 並增強（聽不清楚），血清素作用機制是發育性癲癇性腦病變中經過驗證且眾所周知的作用機制。EPX-100 在斑馬魚模型中顯示出功效，具有 100% 陽性預測值和 100% 陰性預測值。

In addition, EPX-100 mechanism of action is also valuated in other DEE such as impacting binding protein 1 deporter we have preclinical experiments suggesting a broad utility for EPX-100 in DEE. When it comes to safety and tolerability, clemizole was on the market for approximately 20 years with no significant safety and/or tolerability symptoms from post-marketing exposures.

此外，EPX-100 的作用機制也在其他 DEE 中得到評估，例如影響結合蛋白 1 驅逐器，我們的臨床前實驗表明 EPX-100 在 DEE 中具有廣泛的用途。就安全性和耐受性而言，克立咪唑已上市約 20 年，上市後暴露沒有明顯的安全性和/或耐受性症狀。

In addition, EPX-100 favorable preliminary safety and tolerability in the ongoing Phase 3 registration study in Dravet syndrome compared to 7 (inaudible) with no need for additional laboratory or special monitoring.

此外，與 7 期（聽不清楚）相比，EPX-100 在正在進行的 Dravet 症候群 3 期註冊研究中具有良好的初步安全性和耐受性，無需額外的實驗室或特殊監測。

EPX-100 drug is studied in a liquid formulation with [BID] dosing, a simple dosing regimen that is especially meaningful for patients, including the DEEs and their caregivers. We are actively recruiting globally for our Phase III registration study in Dravet syndrome, the ARGUS study and we are on track to start a global Phase 3 registration study in LGS by the end of this year.

EPX-100 藥物以 [BID] 劑量的液體製劑進行研究，這是一種簡單的劑量方案，對患者（包括 DEE 及其照護者）特別有意義。我們正在全球積極招募 Dravet 症候群的 III 期註冊研究（ARGUS 研究），並且我們預計在今年年底前啟動 LGS 的全球 3 期註冊研究。

The strong evidence for efficacy, promising safety and tolerability profile, BID dosing is on track for top line in 2026, makes EPX-100 the most promising and the most advanced investigational drug for DEEs.

功效的有力證據、有希望的安全性和耐受性，BID 劑量有望在 2026 年達到頂線，使 EPX-100 成為 DEE 最有前途和最先進的研究藥物。

We have one more investigation product, EPX-200 or liquid formulation of lorcaserin in the pre-IND phase. Lorcaserin is a selective 5-HT2C agonist and the mechanism of action is well established in DEE. We have preclinical experiments in the zebrafish model and also in the cadence, we are (inaudible) in 2018 in neurology following which the FDA expects interest in exploring lorcaserin in developmental and epileptic encephalopathy.

我們還有一種研究產品 EPX-200 或氯卡色林液體製劑處於預 IND 階段。氯卡色林是一種選擇性 5-HT2C 激動劑，其作用機制在 DEE 中已得到充分證實。我們在斑馬魚模型和節奏中進行了臨床前實驗，我們（聽不清楚）將於2018 年在神經病學領域進行，隨後FDA 預計有興趣探索氯卡色林在發育性和癲癇性腦病變中的應用。

We are currently in the pre-IND phase, and we plan to pursue all DEEs with EPX-200. It is important to note that the safety and tolerability of lorcaserin is also well-established based on the short-term, long-term and real-world outcomes study with lorcaserin. The regulatory agencies recognized the unmet need and the (inaudible) EPX-100 and EPX-200 could potentially offer to patients with DEEs.

我們目前正處於 IND 前階段，我們計劃使用 EPX-200 追求所有 DEE。值得注意的是，基於氯卡色林的短期、長期和現實世界結果研究，氯卡色林的安全性和耐受性也得到了充分證實。監管機構認識到未滿足的需求，並且（聽不清楚）EPX-100 和 EPX-200 可能為 DEE 患者提供服務。

Accordingly, EPX-100 has received both orphan designation and rare pediatric disease designation for both DF and LGS by the FDA. EPX-200 has received orphan drug designation for DF by the FDA and [EMAR], and it has received orphan designation and rare pediatric disease designation for LGS by the FDA.

因此，EPX-100 已獲得 FDA 的 DF 和 LGS 孤兒藥指定和罕見兒科疾病指定。EPX-200已獲得FDA和[EMAR]針對DF的孤兒藥指定，並已獲得FDA針對LGS的孤兒藥指定和罕見兒科疾病指定。

Finally, with our new neurodegenrative franchise, we remain on track to report top line data from the Phase 3 RECONNECT registrational trial of ZYN-002 in Fragile X Syndrome in mid-2025. If approved, this will be the first and only approved treatment for any symptom in patients with Fragile X syndrome. We are also on track to initiate the Phase 3 registration study in 22q11.2 Deletion Syndrome in 2025 under the rare disorder with prominent [neurodegenerative] symptom for which there are no approved treatment.

最後，憑藉我們新的神經退化性疾病特許經營權，我們預計在 2025 年中期報告 ZYN-002 治療脆性 X 綜合徵的 3 期 RECONNECT 註冊試驗的主要數據。如果獲得批准，這將是第一個也是唯一一個獲得批准的針對脆性 X 綜合徵患者任何症狀的治療方法。我們也計劃於 2025 年啟動 22q11.2 缺失症候群的 3 期註冊研究，該症候群是一種具有顯著[神經退化]症狀且尚無批准治療方法的罕見疾病。

In summary, we have made significant progress in advancing our late-stage pipeline across our three (inaudible) and look forward to sharing more in the coming months and years as we continue to make progress. On behalf of HARMONY, I would like to thank all the patients and their families who are participating in our clinical trial as well as the clinical investigators and site personnel for their efforts and commitment in helping us advance our development programs.

總而言之，我們在推進三個階段（聽不清楚）的後期研發管線方面取得了重大進展，並期待在未來幾個月和幾年中隨著我們繼續取得進展分享更多資訊。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 Sandip Kapadia，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 third quarter earnings release and filed our 10-Q where you find the details of our third quarter 2024 financial and operating results.

謝謝你，庫馬爾，大家早安。今天早上，我們發布了第三季財報，並提交了 10-Q 報告，您可以在其中找到我們 2024 年第三季財務和營運業績的詳細資訊。

Our financial performance is also shown on slides 18 through 20. Harmony continues to have a unique profile in the biotech community. We're a profitable, cash-generating company, able to fund the growth and advancement of our pipeline fully off our balance sheet. We delivered another quarter of strong double-digit top line growth, maintained profitability and achieved robust cash generation.

我們的財務表現也顯示在投影片 18 至 20 中。Harmony 在生技界繼續擁有獨特的形象。我們是一家盈利的、產生現金的公司，能夠完全在資產負債表之外為我們的管道的成長和進步提供資金。我們又一個季度實現了兩位數的強勁營收成長，保持了盈利能力並實現了強勁的現金生成。

Our financial performance and strong balance sheet position positions us well to continue advancing our industry-leading pipeline, along with driving excellence in the commercialization of WAKIX in narcolepsy. We reported net revenues of $186 million for the third quarter of 2024 compared to $160.3 million in the prior year quarter. Performance in the quarter reflects the continued strong underlying demand for WAKIX. We also reported total operating expenses for the third quarter of $81.6 million as compared to $63.5 million for the same quarter in 2023, representing a 29% increase.

我們的財務表現和強勁的資產負債表狀況使我們能夠繼續推進業界領先的產品線，同時推動 WAKIX 在嗜睡症領域的商業化取得卓越成就。我們報告 2024 年第三季的淨收入為 1.86 億美元，而去年同期為 1.603 億美元。本季的業績反映了 WAKIX 持續強勁的潛在需求。我們也報告了第三季的總營運支出為 8,160 萬美元，而 2023 年同一季度的總營運支出為 6,350 萬美元，成長了 29%。

The growth in expenses was primarily driven by investments in our expanding late-stage pipeline, along with continued investment for the commercialization of WAKIX in narcolepsy. Non-GAAP adjusted net income for the third quarter of 2024 was $59.6 million or $1.03 per diluted share compared to $58.8 million or $0.97 per diluted share in the prior year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance. Please refer to our press release for a reconciliation of GAAP to non-GAAP results.

費用的成長主要是由於對我們不斷擴大的後期產品線的投資，以及對嗜睡症 WAKIX 商業化的持續投資。2024 年第三季非 GAAP 調整後淨利為 5,960 萬美元，或稀釋後每股收益 1.03 美元，而去年同期為 5,880 萬美元，或稀釋後每股收益 0.97 美元。我們認為非公認會計準則調整後淨利更能反映了基本業務績效。請參閱我們的新聞稿，以了解 GAAP 與非 GAAP 業績的調整表。

We ended the third quarter with $504.7 million of cash, cash equivalents and investments. The balance reflects strong cash generation of $70.5 million from operations which provides us the financial flexibility to execute on our strategy of continuing to grow our pipeline.

截至第三季末，我們的現金、現金等價物和投資為 5.047 億美元。該餘額反映了營運產生的 7,050 萬美元的強勁現金，這為我們提供了財務靈活性，可以執行我們繼續擴大管道的策略。

Looking ahead, we continue to expect quarter-over-quarter growth in net revenues in Q4 of this year. We also expect increases in R&D as we initiate our fourth Phase III registrational trial during the fourth quarter. We are once again reiterating our net revenue guidance for 2024 of $700 million to $720 million, highlighting our progress towards the $1 billion plus opportunity in adult narcolepsy alone.

展望未來，我們繼續預期今年第四季淨收入將環比成長。隨著我們在第四季度啟動第四次三期註冊試驗，我們也預計研發會增加。我們再次重申 2024 年淨收入指引為 7 億至 7.2 億美元，強調我們在成人嗜睡症領域取得的 10 億美元以上機會的進展。

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. As we wrap up our call, I want to emphasize that our momentum at Harmony has never been stronger. We continue to lead in sleep/wake fueled by the strength of our foundational business of WAKIX in narcolepsy and driven by a portfolio that represents the next wave of innovation in this space. We believe that our portfolio of assets in rare epilepsies is the most robust and advanced in the industry for DEEs and we are committed to this area of serious unmet medical need.

謝謝你，桑迪普。在我們結束電話會議時，我想強調，我們 Harmony 的勢頭從未如此強大。在 WAKIX 在嗜睡症方面的基礎業務實力的推動下，在代表該領域下一波創新浪潮的產品組合的推動下，我們繼續在睡眠/覺醒領域處於領先地位。我們相信，我們在罕見癲癇領域的資產組合是 DEE 行業中最穩健和最先進的，我們致力於這一嚴重未滿足醫療需求的領域。

And finally, our catalyst-rich late-stage pipeline is poised to deliver one or more new products or indication launches each year over the next five years with exciting catalysts in idiopathic hypersomnia and Fragile X syndrome coming in the first half of next year. We have the proven talent, resources and conviction that will continue to fuel Harmony's growth story. And we are just getting started.

最後，我們富含催化劑的後期產品線準備在未來五年內每年推出一種或多種新產品或適應症，並在明年上半年推出針對特發性睡眠過度和脆性X 綜合徵的令人興奮的催化劑。我們擁有經過驗證的人才、資源和信念，將繼續推動 Harmony 的成長。我們才剛開始。

Thank you. And I will now turn the call back over to the operator.

謝謝。現在我將把電話轉回給接線生。

Thank you. (Operator Instructions) Greg Suvannavejh, Mizuho.

謝謝。（操作員說明）Greg Suvannavejh，Mizuho。

Thanks so much for taking my question. Congrats on the progress. Your pipeline is so deep. I don't know where to start, but maybe if I could ask just one on the Pitolisant GR and HD strategy as we look out on the horizon, can you just give us a sense of how we should visualize how Wakix and then GR when it comes in potentially 2026, how are you going to manage kind of the coexistence of those two products?

非常感謝您提出我的問題。祝賀取得的進展。你的管道太深了。我不知道從哪裡開始，但也許當我們展望地平線時，我可以問一個關於 Pitolisant GR 和 HD 策略的問題，您能否讓我們了解一下我們應該如何想像 Wakix 和 GR 何時它可能會在2026 年推出，您將如何管理這兩種產品的共存？

And then how is that going to evolve when HD launches? Hopefully in 2028, just trying to visualize what a switch strategy might look like just the commercial kind of positioning if you are in a position to have three products basically in the market at the same time?

那麼當 HD 推出時，情況會如何演變呢？希望在 2028 年，如果您能夠同時在市場上擁有三種產品，那麼只是想想像一下轉換策略可能會是什麼樣子的商業定位？

Yeah, good morning, Graig. Thanks to your question. I think that I'm going to turn to Jeff to expand on that. A lot of it is based on our unique commercial model in terms of enabling us to how to handle that strategy. And Jeff can explain further.

是的，早上好，格雷格。謝謝你的提問。我想我將請傑夫來詳細闡述這一點。其中很大一部分是基於我們獨特的商業模式，使我們能夠處理該策略。傑夫可以進一步解釋。

Now, thanks for the question Graig. So Pitolisant on and Wakix obviously is going to be our foundational business. And we see that as a billion dollar plus opportunity from there in advancing these next generation and life cycle management opportunities.

現在，謝謝格雷格提出的問題。因此，Pitolisant on 和 Wakix 顯然將成為我們的基礎業務。我們認為這是推動下一代和生命週期管理機會的十億美元以上的機會。

Pitolisant GR if you're thinking about that asset target PDUFA in 2026, we see that as a creative opportunity to expand the Pitolisant patient base, not necessarily where physicians are going to be converting established Wakix patients to GR, but GR is likely going to be a product using our commercial model where we can actually activate patients who are formally on Wakix who may have dropped off due to GI side effects or didn't achieve clinical benefit.

Pitolisant GR 如果您正在考慮 2026 年的資產目標 PDUFA，我們認為這是擴大 Pitolisant 患者基礎的一個創造性機會，不一定是醫生將現有的 Wakix 患者轉為 GR，但 GR 很可能會是一種使用我們商業模式的產品，我們可以真正激活正式使用Wakix 的患者，這些患者可能因胃腸道副作用而退出或未獲得臨床益處。

We're going to look to tap into that audience as well as any new patient coming into a physician's office, having the benefit of wakix with a gastro resistant coating and the ability with no titration. We see GR growing in new patients as well as previous wakix patients.

我們將尋求吸引這些受眾以及任何進入醫生辦公室的新患者，讓他們受益於 wakix 的抗胃塗層和無需滴定的能力。我們發現新患者和先前的 wakix 患者的 GR 都在增長。

So not converting existing wakix patients. Then when HD looks to come to market with a target PDUFA date in 2028, given the potential to deliver enhanced efficacy, the potential to treat an indication fatigue that doesn't have any products available today.

所以不改變現有的 wakix 患者。然後，當 HD 預計 PDUFA 上市日期為 2028 年時，考慮到提供增強功效的潛力，以及治療目前沒有任何產品可用的適應症疲勞的潛力。

That when we put that product profile in front of health care professionals, they saw that as a superior product profile that is a product that they embraced, likely converting the vast majority of their wakix patients over to they saw this as another opportunity to engage previous wakix patients.

當我們將該產品簡介放在醫療保健專業人員面前時，他們認為這是一個卓越的產品簡介，是他們所接受的產品，很可能將絕大多數wakix 患者轉變為他們認為這是另一個參與以前的機會瓦基克斯患者。

And they also saw this obviously as an opportunity for new existing patients. So that's kind of how we see these products. They are going to be able to coexist. GR and wakix are going to be incremental to creative opportunities. Co-existing HD is likely the asset where we're going to end up seeing most patients end up just given the potential and the meaningful enhancements and benefits that, that product is going to be able to offer to patients with narcolepsy.

他們也顯然認為這對新的現有患者來說是一個機會。這就是我們如何看待這些產品。他們將能夠共存。GR 和 wakix 將增加創意機會。共存的 HD 很可能是我們最終會看到大多數患者最終看到的資產，因為該產品將能夠為發作性睡病患者提供潛力和有意義的增強和好處。

Okay. Thank you. If I could just squeeze in one just on the Rickson program. Very interesting. Lots of investors have been asking about it just I know that you have talked about the ability or the desire to present additional pre clinical data on the assets wraps provide a fuller picture of what you see in that opportunity. Any further comments on when we might see that data and what exactly you're hoping to show when you're able to present additional data on the erection program. Thanks.

好的。謝謝。如果我能在里克森計劃中擠進一個就好了。非常有趣。許多投資人一直在問這個問題，我知道您已經談到了提供有關資產包裝的額外臨床前數據的能力或願望，可以更全面地了解您在該機會中看到的情況。關於我們何時可以看到這些數據以及當您能夠提供有關安裝計劃的其他數據時您到底希望顯示什麼內容，請發表任何進一步的評論。謝謝。

Hey Graig, good morning. Thank you. Yes. At our presented some data on our orexin-2 receptor agonist where we emphasized the novel chemical structure, the highest potency compared to anything that is publicly available on orexin-2 receptor agonist.

嘿，格雷格，早安。謝謝。是的。當我們展示了有關我們的 orexin-2 受體激動劑的一些數據時，我們強調了新穎的化學結構，與任何公開的 orexin-2 受體激動劑相比，其效力最高。

Great selectivity with over 600 fold, which translates into more than 140 fold margin at orexin-1 receptors and also greater than 1,000 fold selectivity over other 150 targets of interest and also potential for QD dosing. The intent is to disclose additional data at the upcoming scientific meetings. We haven't decided when and where, but we will be providing that information soon.

選擇性超過 600 倍，這意味著對orexin-1 受體的選擇性超過 140 倍，並且比其他 150 個目標靶標的選擇性也超過 1,000 倍，並且還有 QD 給藥的潛力。目的是在即將舉行的科學會議上披露更多數據。我們尚未決定何時何地，但我們將很快提供該資訊。

Yeah, Graig, I think the target for that is we're working with our partner bridge and we're looking to next year at a scientific meeting to share sort of the full preclinical profile of that asset.

是的，格雷格，我認為我們的目標是與我們的合作夥伴橋樑合作，我們希望明年在科學會議上分享該資產的完整臨床前概況。

Okay. Thank you.

好的。謝謝。

Ami Fadia, Needham.

阿米法迪亞，尼達姆。

Hi, good morning. Thanks for taking my question. Could you talk about EPS 100 particularly what gets you excited in terms of differentiation on safety, not only versus epidemic in TLA, but also versus [Beric Asin].

嗨，早安。感謝您提出我的問題。您能否談談 EPS 100，特別是在安全性差異方面讓您感到興奮的地方，不僅與 TLA 的流行病相比，而且與[貝里克·阿辛]。

And as we've seen some of the development plans for Beric Asin, can you talk about your clinical development strategy for this asset beyond LES and DS and how you plan to approach the other DEE space. Thank you.

正如我們已經看到的 Beric Asin 的一些開發計劃，您能否談談您在 LES 和 DS 之外對該資產的臨床開發策略，以及您計劃如何進入其他 DEE 領域。謝謝。

Good morning, Amy. Thank you for your question. We will try to unpack that a little bit yet. We are excited with regards to EPX 100, our advanced program, I'll turn to Kumar just, high level in terms of, the strategy where we are. And some of the, the profile we're seeing now compared to what's in the market and some of the other investigational products, Kumar.

早安，艾米。謝謝你的提問。我們將嘗試稍微解開它。我們對 EPX 100 感到興奮，我們的高級計劃，我將轉向庫馬爾，就我們目前的戰略而言，高水平。我們現在看到的一些配置文件與市場上的產品和其他一些研究產品進行了比較，Kumar。

Thank you, Jeff. Good morning Ami. I know you asked several questions there. So let me start by saying that look, the recent developments have validated our presence in developmental epileptic (inaudible) high and need despite several drugs of significant limitations in terms of efficacy, safety and tolerability. So that's where EPX 100 comes in and has the ability to fill several gaps in this area. First and foremost, let me talk about safety.

謝謝你，傑夫。早上好，阿米。我知道你在那裡問了幾個問題。因此，我首先要說的是，儘管有幾種藥物在功效、安全性和耐受性方面存在顯著局限性，但最近的進展證實了我們在發育性癲癇（聽不清楚）方面的存在和需求。這就是 EPX 100 的用武之地，它有能力填補該領域的多個空白。首先，讓我談談安全。

Clemizole hydrochloride has been in market for over 20 years and no safety signals were observed. It was sunsetted with the introduction of second generation of antihistamines. Number two, the FDA asked us to develop this new chemical activity.

鹽酸克立咪唑已上市 20 多年，未觀察到安全訊號。隨著第二代抗組織胺的推出，這種情況逐漸結束。第二，FDA 要求我們開發這種新的化學活性。

So in support of that, we conducted a full battery of non-clinical tests that include six month repeat dose study in bats. Nine months we could do to study in [Begor] and also juvenile toxicity studies. No safety signals were absurd. We also had a Phase 1 study in healthy volunteers which was where we saw acceptable safety and tolerability and supported for the development of this product.

因此，為了支持這一點，我們進行了全套非臨床測試，其中包括對蝙蝠進行六個月的重複劑量研究。我們可以用九個月的時間進行[Begor]研究以及青少年毒性研究。沒有安全訊號是荒謬的。我們還在健康志願者中進行了第一階段研究，我們看到了可接受的安全性和耐受性，並支持該產品的開發。

This study is being recruited in the US and also outside of US and [DU]. So the protocol went through FDA and also IMA and none of these regulatory asked us to do any additional monitoring. And lastly, we disclosed some preliminary safety data from the ongoing Phase 3 study in a (inaudible) syndrome and also from the long term extension study where we showed it offers significant benefits when it comes to a couple of drugs. Like epidemic in terms of not having to monitor liver function tests routinely and [TFL] not having to monitor cardiac functions like echocardiography to look at cardiac [vul] or hypertension.

這項研究正在美國以及美國以外的地區招募[杜]。因此，該方案通過了 FDA 和 IMA，這些監管機構都沒有要求我們進行任何額外的監控。最後，我們披露了正在進行的（聽不清楚）綜合徵的 3 期研究以及長期擴展研究的一些初步安全數據，我們表明它在涉及幾種藥物時提供了顯著的益處。就像流行病一樣，不需要定期監測肝功能測試，並且 [TFL] 不需要監測心臟功能，例如超音波心動圖來檢查心臟 [vul] 或高血壓。

In terms of how it differentiates specifically from [deicing] perspective. EPX 100 safety profile is better established while [profile] is still in early stages and evolving. Second EPX 100 is administered PID was the deicing PID which is very clinically meaningful, especially in patient with developmental end epileptic encephalopathies because of the nature and the severity of the disorder.

從它與[除冰]角度的具體區別來看。EPX 100 安全概況已得到更好的建立，而 [profile] 仍處於早期階段並不斷發展。第二次給予 PID 的 EPX 100 是除冰 PID，這在臨床上非常有意義，特別是對於患有發育性癲癇末期腦病的患者，因為該疾病的性質和嚴重程度。

And the third thing is this is important. EPX 100 is further along in clinical development. We have been actively recruiting for patients in [dual] syndrome study in us and in Europe and we are about to start a Phase 3 study in lenox gastaut syndrome. And as we mentioned during the call earlier, the regulatory have recognized the promise of EPX 100 had given a drug designation and rare pediatric disease designation for both DS and LGS.

第三件事是這很重要。EPX 100 的臨床開發正在進一步推進。我們一直在美國和歐洲積極招募參與[雙重]綜合症研究的患者，我們即將開始針對 Lenox Gastaut 綜合徵的 3 期研究。正如我們之前在電話會議中提到的，監管機構已經認識到 EPX 100 的承諾，為 DS 和 LGS 提供了藥物指定和罕見兒科疾病指定。

Thanks Kumar. Could you also address how you might approach other? DEs Thank you.

謝謝庫馬爾。您還能談談如何與他人相處嗎？DE 謝謝。

Thank you, Ami. Yes. In the call earlier, I mentioned that we have data preclinical data to show the utility of EPX 100 in others DEs. For example, in syntax finding protein one disorder, where we saw good evidence for Effy. And similarly, we saw efficacy in CDD as well. Right now, our focus is to complete the Phase 3 study in gastaut syndrome and focus on LGS in terms of approaching the others DEEs.

謝謝你，阿米。是的。在先前的電話會議中，我提到我們有臨床前數據來展示 EPX 100 在其他 DE 中的效用。例如，在語法尋找蛋白質一種疾病中，我們看到了 Effy 的良好證據。同樣，我們也看到了 CDD 的功效。目前，我們的重點是完成 Gastaut 綜合徵的 3 期研究，並在接近其他 DEE 方面重點關注 LGS。

We are in the process of evaluating that opportunity because those are heterogeneous disorders. In terms of the nature of the study, we have not determined how exactly to go forward, but we will be pursuing all developmental epileptic and encephalopathies EPX100.

我們正在評估這個機會，因為這些是異質性疾病。就研究的性質而言，我們尚未確定具體如何推進，但我們將研究所有發育性癲癇和腦病 EPX100。

I mean, and I would just add, I think that, you know, these development strategies sort of, you know, start more focused and then the opportunity to go broader, in the DEEs which I think is consistent with, the program now.

我的意思是，我想補充一點，我認為，你知道，這些發展策略開始更加集中，然後有機會在 DEE 中擴大範圍，我認為這與現在的計劃是一致的。

But the the opportunity for, broad DEEs potential gastaut trial is absolutely there. But we are in-line and late stage in the dravet syndrome study and on track to initiate the Phase 3 pillow LGS study before your end.

但廣泛的 DEE 潛在的 Gastaut 試驗的機會絕對存在。但我們正處於 Dravet 症候群研究的後期階段，並有望在您結束之前啟動 3 期枕頭 LGS 研究。

Charles Duncan, Cantor Fitzgerald.

查爾斯鄧肯，坎托菲茨杰拉德。

Hey morning, Jeff and team congrats on the progress in the quarter. I'll make the observation. It's tough to know where to start because of all the pipeline products. But I will start with a commercial question. And that is regarding the percentage of patients, the new patients, the over 250 added what percent come from oxibate versus non-oxibate writers. And then I'm kind of curious why you didn't narrow the guy because it seems like the low end is, is quite attainable. And in your perspective on what would have modulated that.

早安，傑夫和團隊恭喜本季的進展。我會進行觀察。由於管道產品眾多，很難知道從哪裡開始。但我將從一個商業問題開始。這是關於患者的百分比、新患者的百分比、超過 250 名患者的百分比，其中來自 oxibate 與非 oxibate 作家的百分比。然後我有點好奇為什麼你沒有縮小這個範圍，因為低端似乎是可以實現的。從你的角度來看，什麼會調節這一點。

Thanks for your question, Jeff comments on you in terms of where the patients are coming from.

感謝您的提問，傑夫根據患者的來源對您進行了評論。

Sure, great question Charles. And so obviously, we're extremely pleased with the growth we saw in the third quarter, we added incrementally approximately 250 average patients from what we reported the second quarter. And Charles, we're seeing patient growth from both segments of health care professionals. It's probably about maybe 60% of those new patients are being added in from the oxibate.

當然，查爾斯這個問題問得好。顯然，我們對第三季的成長感到非常滿意，與第二季報告相比，我們平均增加了約 250 名患者。查爾斯，我們看到這兩個醫療保健專業人員領域的患者都在成長。這些新患者中約有 60% 是透過奧昔酯治療而加入的。

REMS enrolled health care professionals, about 40% are coming from the non-oxidate and that's a lot of function in terms of there's more patients in the oxybate REMS enrolled health care professionals group, they're larger sleep specialists, they tend to have larger patient practices. We continue to see growth in the depth of prescribing.

REMS 註冊的醫療保健專業人員中，大約40% 來自非氧化物，這是一個很大的功能，因為在氧丁酸REMS 註冊的醫療保健專業人員群體中有更多的患者，他們是更大的睡眠專家，他們往往有更大的睡眠專家病人的做法。我們繼續看到處方深度的成長。

Meaning most of these physicians have experience with wakix. They're finding a second, fifth, tenth, 20th patient in this area. But we're really excited that we continue to see new patients coming out of the non-oxibate REMS enrolled health care professional audience.

這意味著這些醫生中的大多數都有使用 wakix 的經驗。他們正在該地區找到第二個、第五個、第十個、第二十個患者。但令我們感到非常興奮的是，我們繼續看到來自未參加 REMS 註冊的醫療保健專業受眾的新患者。

We know that we have an insulated group that we continue to tap into even with all the oxibate churn. And so we're extremely pleased, we see tremendous growth opportunities on the horizon, 80,000 diagnosed patients and we're going to continue to tap into that audience moving forward.

我們知道，我們有一個孤立的群體，即使有所有的氧化酶流失，我們仍會繼續利用它。因此，我們非常高興，我們看到即將出現的巨大成長機會，80,000 名確診患者，我們將繼續吸引這些受眾。

Charles. And I would just add, I think the pattern of broad clinical utility for wakix, in patients with narcolepsy, it continues to hold true, with regards to the, the ACP universe that we're calling on on Sandip, comments on the position on guidance.

查爾斯.我想補充一點，我認為 wakix 在發作性睡病患者中的廣泛臨床效用模式，對於我們在 Sandip 上呼籲的 ACP 世界來說，它仍然是正確的，對立場的評論指導。

Sure, I mean, look as I mentioned on the call, I mean, we continue to expect quarter over quarter growth going into Q4. What I'd say is, our range even right from the start was relatively narrow, right, $700 million,-- $720 million in sales, which is really 2% sort of in overall range.

當然，我的意思是，正如我在電話會議中提到的，我的意思是，我們繼續預計第四季度將出現季度環比增長。我想說的是，我們的範圍從一開始就相對狹窄，對吧，銷售額為 7 億美元，7.2 億美元，實際上只佔整體範圍的 2%。

So we feel good about the range, we continue to see good momentum and we'll provide an update obviously, once, once the year closed on where we ended up on there, we feel very good about the range right now. And we're, we're comfortable.

因此，我們對這個範圍感覺良好，我們繼續看到良好的勢頭，並且我們將顯然提供更新，一旦今年結束，我們就在那裡結束，我們現在對這個範圍感覺非常好。我們，我們很舒服。

If I may add. -- May I ask a question of Kumar with regard to the ongoing study Phase 3 with 100? I'm really quite intrigued with the patient population. I mean, 26 data is a little bit remote. So how is enrollment going? Are you able to enroll patients that are on epidiolex and [mor] inhibitors? And can you characterize the seizure burden and then persistence into the OLE. Can you provide any additional color on how that trial is going?

如果我可以補充的話。 -- 我可以問庫馬爾一個關於正在進行的第 3 階段 100 研究的問題嗎？我真的對患者群體很有興趣。我的意思是，26 個數據有點遙遠。那麼招生進度如何呢？您是否能夠招募使用 Epidiolex 和 [mor] 抑制劑的患者？您能否描述一下癲癇發作負擔以及 OLE 持續情況？您能否提供更多有關該試驗進展的資訊？

Hey, good morning Charles. I mean, the trial is recruiting asphalt projection. We are recruiting patients actively in us, Canada and Europe and in terms of the study design and the patient population, Charles, it's a pretty standard study design that is standard inclusion exclusion criteria compared to any other dravet syndrome study.

嘿，早安查爾斯。我的意思是，試驗正在招募瀝青投影。我們正在美國、加拿大和歐洲積極招募患者，就研究設計和患者群體而言，Charles，這是一個非常標準的研究設計，與任何其他 Dravet 綜合徵研究相比，它是標準的納入排除標準。

In terms of titration, the duration of the study, the inclusion exclusion criteria, the number of seizure medicines on average, these patients have no child, are in need of good medicines and therefore on average, they tend to be anywhere between three to six anti seizure medications.

在滴定、研究持續時間、納入排除標準、平均癲癇藥物數量方面，這些患者沒有孩子，需要好的藥物，因此平均而言，他們往往在三到六之間抗癲癇藥物。

And that's pretty much what we are seeing in our clinical trial and we disclose some of the safety data, very promising and very supportive and tolerability profile as well. One of the things that we did not mention earlier is actually the impact on appetite as well as you know, many of the drugs that are out there have appetite (inaudible)

這幾乎就是我們在臨床試驗中看到的情況，我們揭露了一些安全數據，這些數據非常有希望、非常有支持性和耐受性。我們之前沒有提到的一件事實際上是對食慾的影響，你知道，許多藥物都有食慾（聽不清楚）

Pretty challenging. Given this patient population already have difficulties with feeding and have weight loss. What we saw with EPX-100 days, it did not stop the appetite and there were no other safety or tolerability signals.

相當具有挑戰性。鑑於該患者群體已經存在進食困難並且體重減輕。我們在 EPX-100 天中看到的情況是，它並沒有阻止食慾，也沒有其他安全或耐受性訊號。

So overall, we are very pleased with how the recruitment is going. The target is 2026, topline. Obviously, our goal is to recruit the study as soon as possible and try to bring this medication to the patients as soon as possible.

總的來說，我們對招募的進展感到非常滿意。目標是 2026 年。顯然，我們的目標是盡快招募研究，並嘗試盡快將這種藥物帶給患者。

Very good. Thank you.

非常好。謝謝。

David Amsellem, Piper Sandler. Please

大衛·阿姆塞勒姆，派珀·桑德勒。請

Hey, thanks. So first question is on the payer landscape and how you're thinking about that as we move through 2025, and particularly how you're thinking about net realized price in '25 versus where it is now, just help us better understand how you're thinking about the landscape, particularly with more generics of sodium oxybate set in the market.

嘿，謝謝。因此，第一個問題是關於付款人的情況，以及在我們進入2025 年時您如何看待這一問題，特別是您如何看待25 年的淨實現價格與現在的情況，只是幫助我們更好地了解您的情況正在考慮前景，特別是市面上有更多仿製藥羥丁酸鈉。

So that's, that's number 10 in the market in the not too distant future. So that's number one. And then number two, I just wanted to ask a clarification question on the to in HD. And regarding dosing, I think at the R&D day, you said that you could safely dose up to five times higher than the highest dose of wakix.

也就是說，在不久的將來，它將成為市場上的第十名。所以這是第一。第二，我只是想問一個關於高清的澄清問題。關於劑量，我認為在研發日，您說您可以安全地使用比 wakix 最高劑量高出五倍的劑量。

I just want to make sure that I have that correct. And I think you earlier in the call, you talked about dosing this 2 times higher. So I just wanted to get a better sense of where you think you could realistically dose pitolisant and HD relative to the legacy formulation. Thanks.

我只是想確保我的說法正確。我想您在電話會議的早些時候，談到了將劑量提高兩倍。因此，我只是想更好地了解相對於傳統配方，您認為可以在哪些方面實際使用 pitolisant 和 HD。謝謝。

Sure. Jeff, do you want to respond to the first question?

當然。傑夫，你想回答第一個問題嗎？

Sure. So David with respect to the payer landscape and how we're thinking about 2025, a lot of the quote contracts have already started to be negotiated for next year. And we see next year's landscape to be very similar to what we see right now. For wakix, there's not a lot of incremental contracting that's necessary. Again, we have a very unique position as sort of the, the lowest branded product relative to the oxybates.

當然。David，關於付款人格局以及我們對 2025 年的看法，許多報價合約已經開始就明年進行談判。我們認為明年的情況與我們現在看到的情況非常相似。對於 wakix 來說，不需要太多增量合約。同樣，我們擁有非常獨特的地位，是相對於羥丁酸鹽而言品牌最低的產品。

So we're less expensive on a whack cost than the branded generic oxybate. And I think that position has afforded us an opportunity to not have to contract. So we see a very favorable landscape moving forward in '25 with respect to generic oxybate coming. We don't anticipate any new generic oxybates in the market in '25. It's likely in 2026, that there may be additional opportunities in there.

因此，我們的成本比品牌仿製藥便宜。我認為這個職位為我們提供了一個不必簽訂合約的機會。因此，我們看到 25 年仿製藥羥丁酸的前景非常有利。我們預計 25 年市場上不會出現任何新的非專利羥丁酸鹽。到 2026 年，那裡可能會有更多機會。

But I think what we've seen and heard from the payers currently is, given the fact that wex is the only non scheduled treatment option for both EDS and cataplexy pairs are finding a place on their formularies for that product. There are no plans that require wakix to be stepped through and oxybate either branded or generic and based upon our negotiations and discussions with pairs, we believe that that position is going to maintain moving forward, gives us great opportunity for patients to have access to the product and a lot of confidence for us to continue to grow the brand.

但我認為我們目前從付款人那裡看到和聽到的是，考慮到 wex 是 EDS 的唯一非定期治療選擇，並且猝倒症對正在該產品的處方集中找到一席之地。沒有計劃要求 wakix 逐步通過並氧化品牌或仿製藥，並且根據我們與配對的談判和討論，我們相信這一立場將繼續向前發展，為我們的患者提供了獲得治療的絕佳機會產品和我們繼續發展品牌的信心。

And David in terms of just to clarify the whole in HD what we shared at Investor Day with regards to we did a small study in terms of with wakix and dosed up to five times. The current label dose and established, -- the safety margins for the development program for pitolisant HD, the target in the development program is to dose up to two times, the maximum labeled dose of wakix in the pitolisant HD program. But safety margins have been established up to 5 times of the current maximum dose.

大衛只是為了澄清我們在投資者日分享的全部內容，我們用 wakix 進行了一項小型研究，劑量高達五次。目前的標籤劑量和既定的，--pitolisant HD 開發專案的安全裕度，開發專案的目標是劑量達到 Pitolisant HD 專案中 Wakix 最大標籤劑量的兩倍。但安全裕度已確定為目前最大劑量的 5 倍。

And just try to what you've mentioned up to 2 times the highest labor dose of li with the optimized formulation, which means that the exposure will be a lot higher milligram to milligram compared to wakix and not only that, we also were able to accomplish some of the things with the optimized formulation, like decrease in inter induced as well, which have meaningful clinical impact in patients.

只需嘗試您提到的最高勞動劑量 2 倍的優化配方，這意味著與 wakix 相比，暴露量將高出毫克到毫克，不僅如此，我們還能夠透過優化的配方完成了一些事情，例如減少了相互作用，這對患者產生了有意義的臨床影響。

Okay. Alright, that's helpful. Thanks.

好的。好的，這很有幫助。謝謝。

Thanks David.

謝謝大衛。

Danielle Brill, Raymond James.

丹妮爾·布里爾，雷蒙德·詹姆斯。

Hi, good morning. Thanks for the questions. I guess Sandeep your guidance for 7,000 patients on drug by year end implies a sequential decline in that patient ads. Is there any particular reason why we might be expecting a slight dip next quarter? And then I just have a clarification on the strategy with DEE, is there any reason to leave this as separate indications from LGS or do you feel a vast study might be better suited for [Loas and verse Clemizole]? I appreciate the clarity there. Thank you.

嗨，早安。感謝您的提問。我猜 Sandeep 您對年底前 7,000 名患者接受藥物治療的指導意味著患者廣告的數量將連續下降。是否有任何特殊原因導致我們預計下季會出現小幅下滑？然後我只是對 DEE 的策略進行澄清，是否有任何理由將其作為 LGS 的單獨指示，或者您是否認為大規模研究可能更適合[洛阿斯和詩句克立咪唑]？我很欣賞那裡的清晰度。謝謝。

Yeah. Hi, Danielle. Thanks for the question. I think overall thought around there was we said approximately 7,000, we're not exactly guiding to exactly 7,000. So I think, what we're seeing is good underlying demand, continued growth quarter-over -quarter. So we don't see any, any reason why there would be a significant again change in terms of momentum going into the fourth quarter. So that's maybe Jeff Dirks. Is there anything else on that?

是的。嗨，丹妮爾。謝謝你的提問。我認為總體想法是我們說大約 7,000 個，但我們並沒有準確指導到 7,000 個。所以我認為，我們看到的是良好的潛在需求，季度環比持續成長。因此，我們看不到任何理由說明第四季的勢頭會再次發生重大變化。所以這可能就是傑夫·德克斯。這上面還有別的事嗎？

No, I would reiterate exactly what Sandip said, guidance is an approximation. We've had very strong durable growth, double digit growth. It's been, been very consistent and so we have a lot of confidence, but yes, it's an approximation. And again, the average number of patients we round to the nearest 50. So Danielle, I would anticipate Q4 to look, similar to what we've sort of seen in momentum in Q2 and Q3.

不，我要重申桑迪普所說的，指導是一個近似值。我們實現了非常強勁的持久成長，兩位數的成長。它一直都非常一致，所以我們很有信心，但是，是的，這只是一個近似值。同樣，我們將患者的平均數量四捨五入到最接近的 50 位。因此，丹妮爾，我預計第四季的情況與我們在第二季和第三季看到的勢頭類似。

In terms of Daniel, in terms of your other question regarding the basket study, look, we know that the regulatory agency is open for a basket study approach.

就丹尼爾而言，就您有關籃子研究的其他問題而言，我們知道監管機構對籃子研究方法持開放態度。

We are pursuing two programs, as we mentioned with EPX 101 in DS and one in LGS. We are taking a measured approach in that LGS is already a heterogeneous disorder. So we want to keep the patient population as homogeneous as possible. But we are definitely exploring the opportunity of a basket study for the rest of the and DEEs on depending on the experience that we will have with EPX-100 clinical development plans for EPX-200

我們正在推行兩項計劃，正如我們所提到的 DS 中的 EPX 101 和 LGS 中的一項。我們正在採取謹慎的方法，因為 LGS 已經是一種異質性疾病。因此，我們希望盡可能保持患者群體的同質性。但我們肯定會根據 EPX-100 和 EPX-200 臨床開發計劃的經驗，探索對其他和 DEE 進行籃子研究的機會

But we are also very excited about EPX-200 liquid formulation of [Loas] gives the mechanism of action, the preclinical evidence for efficacy and also the clinical evidence for efficacy that is published widely in literature in an article by [T and Biki] in 2018 in Neurology.

但我們也非常興奮，[Loas] 的 EPX-200 液體製劑給出了作用機制、臨床前療效證據以及臨床療效證據，這些證據在 [T 和 Biki] 的一篇文章中廣泛發表在文獻中。年神經病學。

Thank you so much.

太感謝了。

Ash Verma, UBS.

阿什‧維爾瑪，瑞銀集團。

Just for [Zygel] in the RECONNECT study. So you have 80% of patients which have this complete retaliation. I wanted to understand why you're studying the noncomplete methylation patients as well. When you look at the data previously, I think the complete methylation patients have been likely to show the benefit and your primary endpoint is also on the complete methylation.

僅限 RECONNECT 研究中的 [Zygel]。所以80%的病人都會有這種徹底的報復。我想了解為什麼您還要研究不完全甲基化患者。當您之前查看數據時，我認為完全甲基化患者可能會顯示出益處，並且您的主要終點也完全甲基化。

Do you have any understanding from the FDA that you could get a level irrespective of the methylation status if the study is positive. And just quickly on the quarter. So is there any like inventory build here from the case so the aggregation number added by 4% -- increased 4% sequentially, but the net sales is up 8%?

FDA 是否知道，如果研究呈陽性，無論甲基化狀態如何，您都可以獲得一個水平。並且很快就到了本季。那麼，是否存在類似的庫存累積情況，因此聚合數量增加了 4%——環比增加了 4%，但淨銷售額卻增加了 8%？

Kumar, could you address the question on ZYN002?

Kumar，您能解決有關 ZYN002 的問題嗎？

So you like the primary target population and the primary endpoint is on patients with complete methylation. There's a normal number of partially metalletic patients as well, and this came about during our discussion with the FDA. If we do see supportive data in partially methalytic patients that's consistent with the data that we see in complete methylation patient that does leave us an opportunity to discuss with the regulatory agency in terms of getting a broader lay power. But for now, the study primary target population and the primary end point is complete methylation patients.

所以你喜歡主要目標族群，主要終點是完全甲基化的病人。部分金屬患者的數量也正常，這是在我們與 FDA 討論期間發生的。如果我們確實在部分甲基化患者中看到支持性數據，這與我們在完全甲基化患者中看到的數據一致，這確實讓我們有機會與監管機構討論以獲得更廣泛的非專業權力。但就目前而言，該研究的主要目標族群和主要終點是完全甲基化患者。

Just a question in terms of trade inventory. I mean we see normal fluctuations of trade inventory every quarter, I'm saying significant that I would mention, at least for that was had an impact this quarter. Typically, what you do see in the second half of the year, you see some improvement in gross to net. The first quarter, as you know, as you go into the year, gross net tends to be higher, starts coming down in the second quarter and the second half of the year tends to be. So what you're probably seeing a little bit of improvement in gross to net as well. So hopefully, that provides some context.

只是貿易庫存方面的問題。我的意思是，我們每季都會看到貿易庫存的正常波動，我想說的是，我會提到這一點，至少在本季產生了影響。通常，您在下半年看到的情況是，毛淨值有所改善。如你所知，隨著今年的到來，第一季的總淨值往往會更高，第二季開始下降，下半年往往會下降。因此，您可能會看到毛淨值也有一些改善。希望這能提供一些背景資訊。

Corinne Jenkins, Goldman Sachs.

科琳·詹金斯，高盛。

Maybe a couple from us. Could you just talk to us about how you're planning to measure fatigue in the clinical study of pitolisant HD and narcolepsy? And how -- like what would be clinically meaningful in terms of benefit on those patient population? And maybe you could just provide some context around how common fatigue is within a narcolepsy population, that would be helpful.

也許是我們當中的一對。您能跟我們談談您計劃如何在pitolisant HD 和發作性睡病的臨床研究中測量疲勞嗎？以及如何－例如什麼對這些病患群體的益處具有臨床意義？也許你可以提供一些有關嗜睡症人群中疲勞常見程度的背景信息，這會有所幫助。

Kumar to plan for fatigue and HD.

庫馬爾為疲勞和 HD 制定計劃。

Yeah, fatigue is a symptom that is more prevalent than one we think in patients with narcolepsy. The literature has indicated that about 60% to 70% of patients with narcolepsy have fatigue and we are doing a longitudinal provenance and impact of 50, 80 patients with narcolepsy. The study is underway, and that is the preliminary data shows the covalent of 38 is very similar.

是的，疲勞是一種在發作性睡病患者中比我們想像的更為普遍的症狀。文獻表明，大約60％至70％的發作性睡病患者有疲勞，我們正在對50、80名發作性睡病患者進行縱向起源和影響。研究正在進行中，初步數據顯示38的共價非常相似。

About 2/3 of the patients with narcolepsy have significant fatigue. In terms of how do we measure, this is an indication for which there are no approved treatments. So we had an extensive leading-edge work. Look at the -- all the instruments that are out there to measure fatigue and we are devoting an instrument that specifically measures fatigue in patients with narcolepsy.

約2/3的發作性睡病患者有明顯的疲勞感。就我們如何衡量而言，這表明尚無批准的治療方法。因此，我們開展了廣泛的前沿工作。看看所有可以測量疲勞的儀器，我們正在開發一種專門測量嗜睡症患者疲勞的儀器。

A lot of work that is can be done and we'll be discussing with the regulatory agencies in terms of the appropriateness of using that instrument specifically to measure fatigue specifically in patients with narcolepsy because that is what the regulatory [SMS] expect.

可以做很多工作，我們將與監管機構討論專門使用該儀器專門測量發作性睡病患者的疲勞程度的適當性，因為這是監管機構 [SMS] 所期望的。

And then in terms of the patents around the pitolisant HD, could you just help expand on the kind of nature and number of those patents that you have into those early 40s?

然後，就 pitolisant HD 的專利而言，您能否幫助擴大您 40 歲出頭所擁有的這些專利的性質和數量？

I think the patent on HD are around the unique formulation with regards to that along with the guest services and coding. And the improvement in the overall PK profile. So the clinical data will sort of support that with regards to what that PK profile will demonstrate. And that is the basis of the HD pass out to the 2044.

我認為 HD 專利圍繞著與客戶服務和編碼相關的獨特配方。以及整體PK形象的提升。因此，臨床數據將在某種程度上支持 PK 曲線所展示的內容。這就是 HD 傳遞給 2044 的基礎。

Jason Gerberry, Bank of America.

傑森‧格伯里，美國銀行。

Two for me. First, just on EPX-100. Wondering, have you looked at EPX-100 relative to long board [Exa] in the zebrafish model? And is that something that's sensitive enough to tease out potential areas of differentiation or more of just a measure of more of a go, no-go viability of the molecule in that disease state.

給我兩個。首先，僅在 EPX-100 上。想知道，您是否在斑馬魚模型中觀察過 EPX-100 相對於長板 [Exa] 的情況？它是否足夠敏感，可以找出潛在的分化區域，或者更多地只是衡量該分子在該疾病狀態下的可行、不可行的生存能力。

And then as we get into next year, just curious with respect to WAKIX IP litigation, there's a markman hearing. I'm just curious if you can kind of help frame what are some of the key kind of outcomes we'd be looking for with respect to the crystal inform patent.

然後，當我們進入明年時，只是對 WAKIX 智慧財產權訴訟感到好奇，將會舉行一場馬克曼聽證會。我只是好奇您是否可以幫助我們確定我們在晶體資訊專利方面尋求的一些關鍵結果。

How important is you get a broad plan construction to sort of box out generics and secure an infringement rolling ultimately when the case goes to trial in '26.

當案件於 26 年開庭審理時，制定一個廣泛的計劃來排除仿製藥並確保侵權行為最終得到解決是多麼重要。

EPX-100 was extensively studied in the fish model, and it showed great efficacy. Similarly, EPX-200 was also studied in this model, which showed great efficacy, which was (inaudible) clinical experience. In terms of [bexacaterine], obviously, it's not our compound and we don't have access to this compound. But within the fish model, there were some analogue ethat were studied that had some pure 5D, 2C agonistic properties and that data is published in the literature by (inaudible) brain communication.

EPX-100在魚類模型中進行了廣泛研究，並顯示出巨大的功效。同樣，EPX-200也在這個模型中進行了研究，顯示出很好的療效，這是（聽不清楚）臨床經驗。就[貝薩卡特林]而言，顯然它不是我們的化合物，而且我們無法獲得這種化合物。但在魚模型中，研究了一些類似的 e，它們具有一些純粹的 5D、2C 激動特性，並且這些數據透過（聽不清楚）大腦通訊發表在文獻中。

And I think, Jason, in terms of your second question about the IP litigation I think, first of all, we can't really comment on ongoing litigation. But I think the [MARC] trial is that scheduled for next March. I mean basically, what that does is it sets up the claims construction I think it sets up the overall claims construction in the case and then informs the plan for the trial in 2026.

我認為，賈森，關於你關於智慧財產權訴訟的第二個問題，我認為，首先，我們無法對正在進行的訴訟發表真正的評論。但我認為 [MARC] 審判定於明年三月進行。我的意思是，基本上，它的作用是建立索賠解釋，我認為它建立了案件的總體索賠解釋，然後告知 2026 年的審判計劃。

So I think that is the purpose of that in terms of the next stage of that process in the IP litigation. And I think that with regards to, as we've said before, we're confident in the strength of the IP, the patents, there were two potential challenges to the USPTO that were denied and those decisions were final. So our position is strengthened the overall IP out to 2030.

所以我認為這就是智慧財產權訴訟下一階段進程的目的。我認為，正如我們之前所說，我們對智慧財產權、專利的實力充滿信心，美國專利商標局面臨兩個潛在的挑戰，但這些挑戰被駁回，這些決定是最終的。因此，我們的立場是加強到 2030 年的整體智慧財產權。

Francois Brisebois, Oppenheimer.

弗朗索瓦·布里斯布瓦，奧本海默。

Can you help just elaborate on the percentage of patients that are both on oxybate and WAKIX and has that changed with time? I'm just trying to gauge also the reimbursement response? Is that been the same? Is it more difficult? You just mentioned there's so much growth that comes from the REMS doctors.

您能幫忙詳細說明一下同時服用 oxybate 和 WAKIX 的患者的百分比嗎？我只是想衡量一下報銷反應？那是一樣的嗎？是不是更難了？您剛才提到，REMS 醫生帶來瞭如此多的成長。

So I'm just wondering if reimbursement has changed? And do you foresee any changes on if orexins come into market in terms of reimbursing all these products and probably pharmacy market?

所以我想知道報銷是否有變化？如果食慾素進入市場，在補償所有這些產品以及可能的藥房市場方面，您是否預計會發生任何變化？

Thanks for hanging in there. Jeff.

謝謝你堅持在那裡。傑夫.

The percentage of patients that are on both WAKIX and an oxybate has been relatively consistent. It's been like low double digits, like in the teens probably for about the last couple of years. And the reimbursement landscape has been modestly consistent with where we are, obviously, with the introduction of more generic oxybate, it's going to be "easier" to potentially get concomitant use certain plans are obviously looking at this category and disease area.

同時使用 WAKIX 和羥丁藥物的患者比例相對一致。這就像過去幾年中十幾歲的低兩位數一樣。顯然，報銷情況與我們目前的狀況略有一致，隨著更通用的羥丁酸的引入，可能會「更容易」同時使用某些顯然針對這一類別和疾病領域的計劃。

But again, remember, this is a rare orphan space, there's not a lot of patients. It's not very high on a managed care plan for a lot of them, it's more costly to put in additional administrative steps given the limited number of patients.

但再次記住，這是一個罕見的孤兒空間，沒有很多病人。對許多人來說，管理式醫療計畫的費用並不是很高，考慮到病患數量有限，採取額外的行政措施的成本更高。

But obviously, moving forward, there's likely going to be a number of potential branded products that could be introduced later in the decade. Obviously, time will tell how managed care will look at this. But overall, rare orphan categories tend to not be as highly managed as other categories given that there's a limited number of patients.

但顯然，展望未來，可能會在本十年稍後推出許多潛在的品牌產品。顯然，時間會告訴我們管理式醫療將如何看待這個問題。但總體而言，由於患者數量有限，罕見孤兒類別往往不像其他類別那樣受到嚴格管理。

It's not a huge budget area. I think our goal is to continue to provide meaningful enhancements. Obviously, the GR and the HD program are really going to be able to hopefully provide some enhanced efficacy. Maybe that can end up helping to potentially reduce the amount of controlled substances patients take, reduce the amount of stimulants potentially oxybate, which obviously would be extremely favorable, not only for the patients but also the payers.

這不是一個巨大的預算區域。我認為我們的目標是繼續提供有意義的增強功能。顯然，GR 和 HD 程式確實有望提供一些增強的功效。也許這最終可能有助於減少患者服用的受管制物質的數量，減少潛在羥化的興奮劑的數量，這顯然不僅對患者而且對付款人都非常有利。

Thank you. At this time, I would like to turn the call back over to Jeff Dayno for any additional or closing remarks.

謝謝。此時，我想將電話轉回傑夫·戴諾（Jeff Dayno）以徵求任何補充或結束語。

Thanks, operator. Thanks, everyone, for joining our call today. We were excited to share with you the progress we are making in our robust late-stage pipeline and look forward to providing future updates. Thanks, and have a great rest of your day.

謝謝，接線生。感謝大家今天加入我們的電話會議。我們很高興與您分享我們在強大的後期管道中取得的進展，並期待提供未來的更新。謝謝，祝您今天休息愉快。

This does conclude today's Harmony Biosciences Third Quarter 2024 Financial Results Conference Call. You may now disconnect your line, and have a wonderful day.

今天 Harmony Biosciences 2024 年第三季財務業績電話會議到此結束。您現在可以斷開線路，度過美好的一天。