ACADIA Pharmaceuticals Inc (ACAD) 2024 Q3 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the third-quarter 2024 ACADIA Pharmaceuticals earnings conference call. (Operator Instructions)

女士們先生們，謝謝你們的支持。歡迎參加 ACADIA 製藥公司 2024 年第三季財報電話會議。（操作員說明）

Please be advised that today's conference is being recorded. I would like now to turn the conference over to Al Kildani, Senior Vice President, Investor Relations and Corporate Communications. Please go ahead.

請注意，今天的會議正在錄製中。我現在將會議交給投資人關係與企業傳播部資深副總裁 Al Kildani。請繼續。

Thank you. Good afternoon and thank you for joining us on today's call to discuss ACADIA's third-quarter 2024 earnings results. Joining me on the call today from ACADIA are Catherine Owen Adams, our Chief Executive Officer, who will provide some opening remarks followed by Brendan Teehan, our Chief Operating Officer and Head of Commercial, who will discuss our strong commercial franchise's DAYBUE on NUPLAZID.

謝謝。下午好，感謝您參加今天的電話會議，討論 ACADIA 2024 年第三季的獲利結果。今天，我們的執行長 Catherine Owen Adams 從 ACADIA 與我一起參加電話會議，她將發表一些開場白，隨後我們的營運長兼商業主管 Brendan Teehan 將在 NUPLAZID 上討論我們強大的商業特許經營權 DAYBUE。

Also joining us today is Liz Thompson, PhD, Executive Vice President, Head of Research and Development, who will provide an update on our pipeline programs; and Mark Schneyer, our Chief Financial Officer, will review the financial results. Catherine will then provide some closing thoughts before we open up the call for your questions.

今天加入我們的還有執行副總裁兼研發主管 Liz Thompson 博士，她將提供我們管道專案的最新資訊；我們的財務長馬克‧施奈爾 (Mark Schneyer) 將審查財務表現。然後，在我們開始詢問您的問題之前，凱瑟琳將提供一些結束語。

We are using supplemental slides, which are available on our website's Events and Presentations section. Before proceeding, I would like to remind you that during our call today, we will make several forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements, including goals, expectations, plans, prospects, growth potential, timing of events, future results, and financial guidance are based on current information, assumptions, and expectations that are inherently subject to change and involve several risks and uncertainties that may cause results to differ materially.

我們正在使用補充幻燈片，這些幻燈片可以在我們網站的活動和簡報部分找到。在繼續之前，我想提醒您，在今天的電話會議中，我們將做出幾項 1995 年《私人證券訴訟改革法案》含義內的前瞻性聲明。這些前瞻性陳述，包括目標、預期、計劃、前景、成長潛力、事件發生時間、未來結果和財務指導，均基於當前資訊、假設和預期，這些資訊、假設和預期本質上會發生變化，並涉及多種風險和不確定性這可能會導致結果出現重大差異。

These factors and other risks associated with our business can be found in our filings made with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of today's date, and we assume no obligation to update or revise these forward-looking statements as circumstances change, except as required by law.

這些因素以及與我們業務相關的其他風險可以在我們向 SEC 提交的文件中找到。請注意，不要過度依賴這些前瞻性陳述，這些陳述僅截至今天為止，我們不承擔隨著情況變化而更新或修改這些前瞻性陳述的義務，除非法律要求。

I'll now turn the call over to Catherine for opening remarks beginning on slide 4.

現在我將把電話轉給凱瑟琳，讓她從幻燈片 4 開始致開幕詞。

Thank you, Al. Good afternoon, everyone, and thank you for joining us. By way of introduction, I'm Catherine Owen Adams, and it's an honor to be speaking with you as the new CEO of ACADIA. I want to take a few moments to share a little about my background and how it aligns with ACADIA's goals and explain why I felt so drawn to join ACADIA.

謝謝你，艾爾。大家下午好，感謝您加入我們。首先介紹一下，我是凱瑟琳歐文亞當斯 (Catherine Owen Adams)，很榮幸能夠作為 ACADIA 新任執行長與您交談。我想花一些時間分享我的背景以及它如何與 ACADIA 的目標保持一致，並解釋為什麼我如此渴望加入 ACADIA。

To begin, I have over 30 years of experience in the pharmaceutical industry, most recently serving as Senior Vice President and General Manager of the US business of Bristol-Myers Squibb and prior to that, leading their international Major Markets business.

首先，我在製藥業擁有 30 多年的經驗，最近擔任 Bristol-Myers Squibb 美國業務的高級副總裁兼總經理，在此之前，領導其國際主要市場業務。

Before that, I spent 25 years at Johnson & Johnson working on both their pharma and med-tech businesses in the EU and US. Throughout my career, I've led teams that have successfully launched and managed drugs across many therapeutic areas, including rare disease and neurology. In the last five years, I've had the privilege of being involved in nine drug launches in the US and internationally, including a number of successful rare disease launches.

在此之前，我在強生公司工作了 25 年，負責在歐盟和美國的製藥和醫療技術業務。在我的職業生涯中，我所領導的團隊成功地推出和管理了許多治療領域的藥物，包括罕見疾病和神經病學。在過去的五年中，我有幸參與了美國和國際上的九項藥物上市，其中包括許多成功的罕見疾病上市。

I joined ACADIA because I was excited by the foundational business and the future potential of the pipeline. I'm both inspired and humbled to have the opportunity to lead ACADIA in advancing therapies that can make a real difference in people's lives.

我加入 ACADIA 是因為我對基礎業務和管道的未來潛力感到興奮。能夠有機會領導 ACADIA 推進能夠真正改變人們生活的療法，我既感到鼓舞又感到謙卑。

As I look towards that future, I see incredible opportunities ahead to grow our current portfolio and advance the innovations in our pipeline, including two late-stage assets, serving new communities of patients with high unmet medical needs. I see significant potential to enhance shareholder value as we continue to execute and evolve our commercial priorities and advance our pipeline assets.

當我展望未來時，我看到了巨大的機會來擴大我們目前的產品組合併推進我們管道中的創新，其中包括兩項後期資產，為醫療需求未得到滿足的新患者群體提供服務。隨著我們繼續執行和發展我們的商業優先事項並推進我們的管道資產，我看到了提高股東價值的巨大潛力。

Please turn to slide 5, where I will elaborate a little on each of these areas and underline why I chose to join ACADIA against our three core pillars. First, on the commercial front. We have two growing franchises which together, based on our Q3 results, are now tracking to over $1 billion in annualized sales, an extraordinary milestone for a biotech company of our size.

請轉到投影片 5，我將在其中詳細闡述每個領域，並強調為什麼我選擇加入 ACADIA 來反對我們的三個核心支柱。首先，在商業方面。我們擁有兩個不斷增長的特許經營權，根據我們第三季度的業績，它們的年銷售額目前已超過 10 億美元，這對於我們這樣規模的生物技術公司來說是一個非凡的里程碑。

Second, our robust pipeline includes two late-stage assets in Prader-Willi syndrome and Alzheimer's disease psychosis, complemented by many promising early-stage programs. And third, our financial strength is fueled by our positive cash flows and a growing cash balance, which now stands at $565 million.

其次，我們強大的產品線包括普瑞德威利症候群和阿茲海默症精神病領域的兩個後期資產，並輔以許多有前景的早期計畫。第三，我們的財務實力得益於我們的正現金流和不斷增長的現金餘額，目前現金餘額為 5.65 億美元。

I'll now briefly highlight our commercial and R&D pillars before handing off to our leaders, who will dive deeper into the details.

現在，我將簡要強調我們的商業和研發支柱，然後再交給我們的領導者，他們將更深入地探討細節。

Turning now to slide 6. Beginning with DAYBUE where we've had another solid quarter, generating sales of $91.2 million, up 36% year over year and 8% sequentially. I'd like to take this opportunity to share some high-level observations on DAYBUE based on my experience with multiple rare disease launches and to give some context for our launch results to date.

現在轉到投影片 6。從 DAYBUE 開始，我們又取得了一個穩定的季度業績，銷售額達到 9,120 萬美元，年增 36%，環比成長 8%。我想藉此機會根據我在多次罕見疾病上市的經驗，分享對 DAYBUE 的一些高層觀察，並為我們迄今為止的上市結果提供一些背景資訊。

Six quarters in, with $429 million generated in sales, I think we can claim this has been a successful launch. Every rare disease launch is unique, but I have observed some key commonalities with DAYBUE. They are complex, highly situational, and involve coordination of lots of moving parts within the healthcare system. Especially important is the focus on the patient's journey, both to start and stay on therapy and concentrating on how this journey is fully supported.

六個季度以來，銷售額達到 4.29 億美元，我認為我們可以說這是一次成功的發布。每一次罕見疾病的推出都是獨一無二的，但我觀察到 DAYBUE 的一些關鍵共通點。它們很複雜、高度情境化，並涉及醫療保健系統內許多活動部分的協調。尤其重要的是專注於患者的旅程，包括開始和繼續治療，以及如何充分支持這趟旅程。

We've reached a steady state of new patient starts with DAYBUE and have strengthened our focus on growing this in the next several quarters. This will take time, and growth will be driven by continuing to lean into the breadth of our clinical data, illustrating and describing to HCPs the impact DAYBUE has on patients, bringing to life the scoring system used in clinical trials and generating real-world experience and insights from our ongoing LOTUS study.

我們已經達到了新患者從 DAYBUE 開始的穩定狀態，並加強了我們對未來幾季成長的關注。這需要時間，而增長將透過繼續深入臨床數據的廣度、向 HCP 說明和描述 DAYBUE 對患者的影響、使臨床試驗中使用的評分系統栩栩如生並產生真實經驗來推動。見解。

We will also continue to focus on the early part of the patient journey as families and doctors work together to find the dose for their trials. I'm extremely confident about the potential for DAYBUE growth and further penetration beyond our COEs into the diagnosed patients who can benefit from its impact, both in the US and beyond.

我們也將繼續關注患者治療過程的早期階段，讓家人和醫生共同努力尋找試驗劑量。我對 DAYBUE 的成長潛力以及進一步滲透到我們的 COE 之外的診斷患者中非常有信心，這些患者可以從其影響中受益，無論是在美國還是其他地區。

I'll now turn to NUPLAZID, which has had an outstanding quarter with net sales of $159.2 million, up 10% year over year. These results were achieved on the basis of underlying trends we described last quarter, including the impactful real-world evidence studies and last year's label clarification, combined with what we now see as a stable Parkinson's disease psychosis market.

現在我要談談 NUPLAZID，該公司季度業績表現出色，淨銷售額為 1.592 億美元，年增 10%。這些結果是在我們上季度描述的基本趨勢的基礎上實現的，包括有影響力的現實世界證據研究和去年的標籤澄清，再加上我們現在看到的穩定的帕金森氏症精神病市場。

In August, in collaboration with Ryan Reynolds, we announced our unbranded More to Parkinson's campaign to raise awareness of Parkinson's related hallucinations and delusions. We are excited about the early impact of this campaign that we're seeing with patients and caregivers and HCPs.

8 月，我們與 Ryan Reynolds 合作，宣布了無品牌的 More to Parkinson's 活動，以提高人們對帕金森氏症相關幻覺和妄想的認識。我們對這項活動對患者、照護者和醫護人員產生的早期影響感到興奮。

Separately, we launched a new classic direct-to-consumer campaign, which we believe will help us accelerate growth for NUPLAZID in 2025. Brendan will discuss these campaigns in more detail.

另外，我們也推出了一項新的經典的直接面向消費者的活動，我們相信這將有助於我們在 2025 年加速 NUPLAZID 的成長。布倫丹將更詳細地討論這些活動。

Turning now to slide 7 for a discussion of our pipeline. In addition to our successful commercial brands, ACADIA's pipeline is an important reason why I was so excited to join the company as I believe the pipeline is truly underappreciated. We have a Phase 3 asset in ACP-101 that's being evaluated as a treatment for Prader-Willi syndrome, a rare and debilitating genetic disease with no FDA-approved treatment, where patients often have an unrelenting drive to eat called hyperphagia. Behind that in our pipeline is ACP-204, our second-generation 5-HT2A blocker, while we are currently conducting the Phase 2 portion of the program.

現在轉到投影片 7 來討論我們的流程。除了我們成功的商業品牌之外，ACADIA 的產品線也是我如此興奮加入該公司的一個重要原因，因為我相信該產品線確實被低估了。我們擁有ACP-101 的3 期資產，正在評估其用於治療Prader-Willi 症候群的方法，這是一種罕見且使人衰弱的遺傳性疾病，尚無FDA 批准的治療方法，患者常常有一種持續不斷的進食慾望，稱為食慾過盛。我們的研發管線背後是 ACP-204，我們的第二代 5-HT2A 阻斷劑，而我們目前正在進行該計劃的第二階段部分。

This exciting asset has the potential to extend and expand our neuropsychiatry franchise. Both of these drugs will allow us to offer new options for patients in underserved communities with patient numbers larger than our current portfolio. We also have a number of exciting earlier-stage assets. We look forward to discussing more in the future as they advance in their development.

這一令人興奮的資產有可能擴展和擴大我們的神經精神病學專營權。這兩種藥物將使我們能夠為服務不足的社區的患者提供新的選擇，這些社區的患者人數超過我們目前的產品組合。我們還擁有許多令人興奮的早期資產。隨著他們的發展，我們期待在未來進行更多討論。

We're also actively pursuing opportunities to expand this pipeline further through business development, which remains a strategic imperative of the company and an important focus for me as we look to set our growth trajectory for the future.

我們也積極尋求機會，透過業務發展進一步擴大這一管道，這仍然是公司的策略要務，也是我在製定未來成長軌跡時的一個重要關注點。

I'll now turn it over to Brandon to discuss our commercial performance of these brands beginning on slide 8.

我現在將把它交給 Brandon，從幻燈片 8 開始討論這些品牌的商業表現。

Thank you, Catherine. Let's take a look at both our DAYBUE and NUPLAZID franchises, starting first with DAYBUE on slide 9.

謝謝你，凱瑟琳。讓我們來看看我們的 DAYBUE 和 NUPLAZID 特許經營權，首先從幻燈片 9 上的 DAYBUE 開始。

In Q3, we continued to drive growth in our DAYBUE business with $91.2 million in net sales. That growth was primarily driven by continued penetration of the prevalent population and increased demand as measured by dispense rates among our continuing patients.

第三季度，我們繼續推動 DAYBUE 業務的成長，淨銷售額為 9,120 萬美元。這種增長主要是由於流行人群的持續滲透和需求的增加（以我們的持續患者的配藥率來衡量）所推動的。

During the quarter, 923 patients received paid shipments, which compares to 917 receiving shipments in Q2 and 871 in Q1. Importantly, the average `number of bottles each patient received increased as our patient cohorts mature and begin reaching a dose that they will likely remain on longer term.

本季度，有 923 名患者收到了付費發貨，而第二季度有 917 名患者收到了付款，第一季度有 871 名患者收到了付款。重要的是，隨著我們的患者群體成熟並開始達到他們可能長期保持的劑量，每個患者收到的平均「瓶子數量」會增加。

Weekly patient discontinuations in the quarter were similar to Q2 and continued to be down significantly from Q1. Importantly, we now have over 60% of all active DAYBUE patients on treatment for 10 months or more since treatment initiation.

本季每週患者停藥情況與第二季相似，且比第一季持續顯著下降。重要的是，自治療開始以來，我們現在有超過 60% 的活躍 DAYBUE 患者接受了 10 個月或更長時間的治療。

This is significant as the persistency curve for patients out past 10 months on treatment is flattening, suggesting a strong enduring patient base benefiting from treatment over time. In fact, looking out 12 months and beyond, we see persistency rates at 50% or higher. This compares favorably to other chronic therapies at similar stages.

這一點意義重大，因為過去 10 個月接受治療的患者的持續性曲線正在趨於平坦，這表明隨著時間的推移，強大的持久患者基礎會從治療中受益。事實上，展望 12 個月及以後，我們發現持久率達到 50% 或更高。這與類似階段的其他慢性療法相比具有優勢。

Turning to prescriber dynamics. We have continued to expand the breadth of prescribers with now approximately 800 unique prescribers having written a prescription for DAYBUE. We have further increased our penetration of the 21 Rett Center of Excellence or COEs, and we see an increasingly large proportion of new starts coming from non-COE high-volume institutions as well as community-based practices.

轉向處方者動態。我們繼續擴大處方者的範圍，目前已有約 800 名獨特的處方者開出了 DAYBUE 的處方。我們進一步提高了對 21 個 Rett 卓越中心或 COE 的滲透率，我們看到越來越多的新項目來自非 COE 的高容量機構以及基於社區的實踐。

This is important as approximately 70% of all Rett patients are treated outside of COEs. We are focusing on driving depth of prescribing among those HCPs who have prescribed DAYBUE to one or two patients, where we know they have additional patients under their care who can also benefit from DAYBUE.

這一點很重要，因為大約 70% 的 Rett 患者在 COE 之外接受治療。我們的重點是提高那些為一到兩名患者開出 DAYBUE 處方的 HCP 的處方深度，我們知道他們還有其他接受治療的患者也可以從 DAYBUE 中受益。

Let's discuss our ongoing efforts to drive future adoption. Please turn to slide 10. As Catherine mentioned, to expand treatment to more of the prevalent Rett patient population, we are focusing on further educating prescribers about DAYBUE's efficacy and the real-world day-to-day benefits patients and their families are experiencing. This is especially important outside of COEs where HCPs do not have as deep an understanding of Rett syndrome or DAYBUE's efficacy profile.

讓我們討論一下我們為推動未來採用所做的持續努力。請翻到投影片 10。正如 Catherine 所提到的，為了將治療範圍擴大到更多的 Rett 患者群體，我們致力於進一步向處方者宣傳 DAYBUE 的功效以及患者及其家人正在經歷的現實日常益處。這在 COE 之外尤其重要，因為 HCP 對 Rett 症候群或 DAYBUE 的療效概況沒有那麼深入的了解。

These caregiver and HCP reported real-world benefits include improved quality of life, improved mood, more purposeful use of hands, increased alertness and better engagement in conversations, and improvement in both verbal and nonverbal communication skills, which among other benefits, are the driving force behind continued penetration of the Rett population.

這些護理人員和 HCP 報告的現實好處包括提高生活品質、改善情緒、更有目的地使用雙手、提高警覺性和更好地參與對話，以及提高語言和非語言溝通技巧，這些好處是推動持續滲透雷特人口的背後力量。

As an example of these tangible daily benefits, I was excited to speak to one of our caregivers at a recent program about what her daughter is now capable of doing on her own now that she's been treated with DAYBUE. She shared that since her eight-year-old daughter started treatment, she can now grab and hold on her own everyday items like utensils and other objects, including much to her delight, ice cream cones. Her daughter has become more expressive and increase her vocalizations, improving her overall ability to communicate as well.

作為這些日常切實好處的一個例子，我很高興在最近的一個計畫中與我們的一位護理人員談論她的女兒在接受 DAYBUE 治療後現在能夠獨立做些什麼。她分享說，自從她八歲的女兒開始接受治療以來，她現在可以抓住並握住自己的日常用品，如餐具和其他物品，其中包括令她高興的蛋捲冰淇淋。她的女兒變得更加富有表現力，發聲能力也增強了，整體溝通能力也提高了。

Other caregivers tell us about their loved ones improved ability to communicate nonverbally with their Tobii eye gaze device. Each of these benefits are helping create better connections with Rett patients and their caregivers.

其他照護人員告訴我們，他們的親人使用 Tobii 凝視設備提高了非語言溝通的能力。這些好處都有助於與 Rett 患者及其照護者建立更好的聯繫。

These are just a few very tangible and exciting examples of the real-world benefits we want all HCPs and caregivers to hear, understand, and pursue. We are sharing these stories within the Rett community where these types of improvements will surely resonate.

這些只是我們希望所有 HCP 和護理人員聽到、理解和追求的現實好處的一些非常切實和令人興奮的例子。我們正在 Rett 社群內分享這些故事，這些類型的改進肯定會引起共鳴。

One of our best sources of real-world efficacy is our ongoing LOTUS observational study that continues to yield valuable insights for both HCPs and families about the number and breadth of clinical benefits caregivers are reporting in their loved ones as well as their GI management experiences. We are sharing this data with HCPs to allow them to make more informed prescribing decisions for their Rett patients.

我們正在進行的LOTUS 觀察性研究是我們真實世界療效的最佳來源之一，該研究持續為HCP 和家庭提供有價值的見解，了解護理人員報告的親人臨床福利的數量和廣度以及他們的胃腸道管理經驗。我們正在與 HCP 分享這些數據，以便他們能夠為 Rett 患者做出更明智的處方決定。

In summary, our primary focus for growth is on demonstrating DAYBUE's efficacy and real-world benefits in our sales materials, peer-to-peer engagements, and our caregiver programming, sharing these benefits with all HCPs and families. We continue to increase penetration of the Rett population and are building a strong and enduring patient base.

總而言之，我們成長的主要重點是在我們的銷售材料、點對點參與和護理人員計劃中展示 DAYBUE 的功效和現實好處，並與所有 HCP 和家庭分享這些好處。我們繼續提高雷特人群的滲透率，並正在建立強大而持久的患者基礎。

We're confident in our growth outlook based on the current rate of new patients entering at the top of the funnel, combined with the growing base of enduring patients. And we plan to continue to drive growth while helping HCPs and families better manage tolerability challenges and improve the early treatment journey. With now over 30% of the 5,000 and growing diagnosed Rett patients in the US having started DAYBUE, we have a substantial opportunity ahead of us to continue growing the brand.

基於目前進入漏斗頂部的新患者的比率以及不斷增長的持久患者基礎，我們對我們的成長前景充滿信心。我們計劃繼續推動成長，同時幫助醫療保健專業人員和家庭更好地應對耐受性挑戰並改善早期治療過程。目前，美國 5,000 名且不斷增加的確診 Rett 患者中，超過 30% 已經開始使用 DAYBUE，我們面臨著繼續發展品牌的巨大機會。

Now let's turn to NUPLAZID on slide 11. Q3 was another outstanding quarter for the NUPLAZID franchise with $159.2 million in net sales, representing the highest ever quarterly sales for the brand with 10% growth year over year. We achieved this growth by increasing active patients on NUPLAZID across all market segments. This strong performance in the quarter follows what we've seen throughout the year as we've grown demand quarter over quarter throughout 2024.

現在讓我們轉向幻燈片 11 上的 NUPLAZID。第三季度是 NUPLAZID 特許經營權另一個出色的季度，淨銷售額為 1.592 億美元，創下該品牌有史以來最高的季度銷售額，同比增長 10%。我們透過增加所有細分市場中 NUPLAZID 的活躍患者數量來實現這一增長。本季的強勁表現延續了我們全年的表現，因為我們在 2024 年全年的需求逐季成長。

Q3 volume growth was driven by two key initiatives that have been the focus of our discussions with HCPs. First, leveraging the published real-world evidence demonstrating the important differential outcomes Parkinson's disease psychosis patients have experience with NUPLAZID, including a lower overall risk of all-cause mortality versus all other off-label antipsychotics, most notably low-dose quetiapine; and educating the market about last year's label clarification, which helps HCPs understand that they can treat Parkinson's disease patients experiencing hallucinations and delusions with or without comorbid dementia. These two levers helped us increase HCP conviction in NUPLAZID as their first-line therapy of choice for PDP, leading to a higher demand and market share.

第三季銷售成長是由兩項關鍵措施推動的，這兩項措施一直是我們與 HCP 討論的焦點。首先，利用已發表的現實世界證據證明帕金森氏症精神病患者使用NUPLAZID 所獲得的重要差異結果，包括與所有其他標籤外抗精神病藥物（尤其是低劑量喹硫平）相比，全因死亡率的整體風險較低；對市場進行有關去年標籤澄清的教育，這有助於醫療保健專業人員了解他們可以治療患有幻覺和妄想並伴有或不伴有癡呆症的帕金森病患者。這兩個槓桿幫助我們增強了 HCP 對 NUPLAZID 作為 PDP 一線治療選擇的信心，從而帶來了更高的需求和市場份額。

Looking at the broader market, we are seeing a return of Parkinson's patients as measured by in-office visits as well as long-term care resident census numbers. This market dynamic supports continued future growth for NUPLAZID. We are excited about NUPLAZID's Q3 results, which were achieved in advance of the benefits we expect to see from our recently launched direct-to-consumer campaigns, which I'll discuss now.

縱觀更廣泛的市場，我們看到帕金森氏症患者的回歸（根據就診人數和長期照護居民人口普查數據來衡量）。這種市場動態支持 NUPLAZID 未來的持續成長。我們對 NUPLAZID 第三季的業績感到興奮，這些業績是在我們期望從最近推出的直接面向消費者的活動中看到的收益之前實現的，我現在將討論該活動。

Please turn to slide 12. As we announced in August, we launched an unbranded disease state education campaign featuring Ryan Reynolds and his mother, Tammy, focused on the non-motor symptoms of hallucinations and delusions that can often accompany Parkinson's disease. The early results of this disease state awareness campaign suggest it is among the most successful campaigns ever in this category. Here are just a couple of the impressive early measures demonstrating this.

請翻到投影片 12。正如我們在 8 月宣布的那樣，我們發起了一項由 Ryan Reynolds 和他的母親 Tammy 主演的無品牌疾病狀態教育活動，重點關注帕金森氏症經常伴隨的幻覺和妄想的非運動症狀。這項疾病狀態意識活動的早期結果表明，它是此類活動中有史以來最成功的活動之一。以下是一些令人印象深刻的早期措施，證明了這一點。

Over 3.9 billion media impressions in just the first eight weeks or so of airing and nearly 200 media placements, including approximately 75% with headline mentions of the campaign. These are very encouraging early indicators.

僅在播出的前八週左右，媒體曝光量就超過 39 億次，媒體投放量近 200 次，其中大約 75% 的標題提到了該活動。這些都是非常令人鼓舞的早期指標。

Concurrently, we also launched a branded campaign featuring NUPLAZID as the first and only treatment for PDP. In just the first two weeks post campaign, we saw a nearly three-fold increase in Parkinson's disease patients who visited nuplazid.com and subsequently visited a PD specialist. As a reminder, we expect the vast majority of the benefit of these campaigns to be seen in 2025 as new patient-scheduled appointments with their specialists and seek treatment for hallucinations and delusions with NUPLAZID in the months ahead.

同時，我們也發起了一項品牌活動，將 NUPLAZID 作為 PDP 的第一個也是唯一的治療方法。在活動結束後的前兩週，我們發現訪問 nuplazid.com 並隨後拜訪帕金森氏症專家的帕金森氏症患者數量增加了近三倍。提醒一下，我們預計這些活動的絕大多數好處將在 2025 年體現為新的患者與專家預約並在未來幾個月內透過 NUPLAZID 尋求幻覺和妄想治療。

In summary, we're excited about the growth we're seeing in NUPLAZID. And we'll look to capitalize on that momentum with our consumer campaigns in the weeks and months ahead.

總之，我們對 NUPLAZID 的成長感到興奮。我們將在未來幾週和幾個月內透過我們的消費者活動來利用這一勢頭。

I'll now turn it over to Liz on slide 13.

我現在將投影片 13 上的內容轉交給 Liz。

Thanks, Bren. Please turn to slide 14.

謝謝，布倫。請翻到投影片 14。

I'd like to start today highlighting some good news on the global expansion front. We recently received approval from Health Canada for DAYBUE as the first and only approved therapy for patients in Canada living with Rett syndrome.

我想從今天開始強調全球擴張方面的一些好消息。我們最近獲得加拿大衛生部批准 DAYBUE 作為加拿大第一個也是唯一一個批准治療雷特氏症患者的療法。

Our next focus is in the EU, where we are targeting a submission of the marketing authorization application in the first quarter of next year. We're now building up our team and expertise in Europe in order to plan for that launch.

我們的下一個重點是歐盟，我們的目標是在明年第一季提交行銷授權申請。我們現在正在歐洲建立我們的團隊和專業知識，以便為該發布做好計劃。

In addition to European expansion, we've had productive conversations with PMDA, the regulatory agency in Japan, regarding the potential to bring DAYBUE to patients there. We very much look forward to continuing to collaborate with PMDA and Japanese experts to progress our clinical program. Continuing on regarding support of our marketed medications, I'd also like to touch upon some of the analyses that we continue to generate and share about NUPLAZID on slide 15.

除了歐洲擴張之外，我們還與日本監管機構 PMDA 就將 DAYBUE 帶給那裡的患者的潛力進行了富有成效的對話。我們非常期待繼續與 PMDA 和日本專家合作，推進我們的臨床計畫。繼續討論對我們已上市藥物的支持，我還想談談我們在幻燈片 15 上繼續生成和分享的有關 NUPLAZID 的一些分析。

At the recent Movement Disorder Society meeting, we presented data on sedation and sleep. Both sleep quality and the avoidance of the unwanted sedation are key areas of interest for physicians treating Parkinson's disease psychosis. In some of the studies with pimavanserin across healthy volunteers, patients with PDP, and patients with neuropsychiatric symptoms related to a neurodegenerative disease, we've included various exploratory measures of sleep. Taken together, the data across these trials suggested that pimavanserin may be associated with low levels of sedation and other sleep-related adverse events.

在最近的運動障礙協會會議上，我們展示了有關鎮靜和睡眠的數據。睡眠品質和避免不必要的鎮靜是治療帕金森氏症精神病的醫生關注的關鍵領域。在一些針對健康志願者、PDP 患者以及患有與神經退化性疾病相關的神經精神症狀的患者中使用匹馬範色林的研究中，我們納入了各種探索性的睡眠測量方法。總而言之，這些試驗的數據表明匹馬範色林可能與低水平鎮靜作用和其他與睡眠相關的不良事件有關。

Just last week, we also presented data at the Psych Congress meeting, examining patients in our PDP studies who had complete resolution of their hallucinations and delusions. The literature suggests that symptoms of Parkinson's disease psychosis will tend to worsen over time, if left untreated. But there's little information about the impact of treating earlier versus later.

就在上週，我們還在心理學大會上公佈了數據，對 PDP 研究中幻覺和妄想完全消失的患者進行了檢查。文獻表明，如果不及時治療，帕金森氏症精神病的症狀會隨著時間的推移而惡化。但關於早期治療與晚期治療的影響的資訊很少。

In an integrated analysis, including 135 patients with PDP, of whom 21 reported no symptoms after receiving pimovanserin. Treatment initiated sooner after onset of hallucinations and delusions was associated with a higher probability of achieving a complete response than much later treatment.

在一項綜合分析中，包括 135 名 PDP 患者，其中 21 名患者在接受匹莫凡色林治療後沒有出現任何症狀。幻覺和妄想出現後較早開始的治療比晚得多的治療獲得完全緩解的可能性更高。

Turning to slide 16, I'll discuss our late-stage clinical programs starting with the ACP-101 program in Prader-Willi syndrome. As a reminder, Prader-Willi is a rare, genetic neurobehavioral disorder. Roughly 8,000 to 10,000 patients in the US are living with Prader-Willi.

轉向投影片 16，我將討論我們的後期臨床項目，從普瑞德威利症候群的 ACP-101 項目開始。提醒一下，普瑞德威利症是一種罕見的遺傳性神經行為障礙。美國約有 8,000 至 10,000 名患有 Prader-Willi 病的患者。

As we've described before, the defining characteristic is hyperphagia, which is an unrelenting hunger. This manifests very early in life and can lead to obesity and myriad complications like Type 2 diabetes or heart disease as well as behavioral changes like anxiety and aggression. And unfortunately, life expectancy is currently only around 30 years old, largely due to cardiovascular disease.

正如我們之前所描述的，其定義特徵是食慾過盛，即一種無情的飢餓感。這在生命的早期就表現出來，可能導致肥胖和多種併發症，如第 2 型糖尿病或心臟病，以及行為改變，如焦慮和攻擊性。不幸的是，目前預期壽命只有 30 歲左右，這很大程度上是由於心血管疾病造成的。

Our Phase 3 study called COMPASS PWS is currently enrolling. This study is global, multicenter, randomized, double-blind and placebo controlled. We built on prior Phase 3 experience in terms of both dose and endpoint selection.

我們名為 COMPASS PWS 的第三階段研究目前正在招募中。這項研究是全球、多中心、隨機、雙盲和安慰劑對照的。我們在劑量和終點選擇方面建立在先前的 3 期經驗基礎上。

We've been truly pleased with the enthusiasm we are seeing in the Prader-Willi community, and we look forward to continuing to work with them and clinical experts as we advance through the study. I anticipate providing more specific guidance on timing early next year.

我們對 Prader-Willi 社區的熱情感到非常滿意，我們期待在研究進展過程中繼續與他們和臨床專家合作。我預計明年初會就時間安排提供更具體的指導。

Now turning to our second late-stage clinical program, ACP-204, on slide 17. Here, we have utilized our extensive neuropsychiatry expertise and pathway understanding to develop a next-generation 5-HT2A compound, designed to build upon the strong product profile of NUPLAZID.

現在轉向幻燈片 17 上的第二個後期臨床項目 ACP-204。在這裡，我們利用豐富的神經精神病學專業知識和通路理解來開發下一代 5-HT2A 化合物，旨在建立在 NUPLAZID 強大的產品特徵之上。

In particular, to date, we've seen no sign of QT prolongation at the doses we are studying, a wide dose range, supporting the potential for a dose equivalent to approximately twice the approved NUPLAZID 34-milligram dose and steady state PK achieved in less than half the time of NUPLAZID, projecting the potential for an earlier onset of activity.

特別是，迄今為止，我們在研究的劑量下沒有看到 QT 延長的跡象，劑量範圍很寬，支持劑量相當於批准的 NUPLAZID 34 毫克劑量的大約兩倍的潛力，並實現了穩態 PK。到NUPLAZID 時間的一半，預計有可能更早開始活動。

Currently, ACP-204 is in development as a potential treatment for Alzheimer's disease psychosis in a master protocol that includes a Phase 2 and two Phase 3s. The program is global and contains randomized, double-blind, placebo-controlled studies.

目前，ACP-204 正在開發中，作為阿茲海默症精神病的潛在治療方法，其主要方案包括一個 2 期和兩個 3 期。該計劃是全球性的，包含隨機、雙盲、安慰劑對照研究。

The Phase 2 is over 300 patients. We continue to plan that the two Phase 3 studies will be of roughly equivalent size. Once the Phase 2 study data are collected, we'll analyze and report results, by which time the two Phase 3 studies will already be underway. I look forward to also providing more specific timing guidance on this program early next year.

第二階段有超過300名患者。我們繼續規劃兩項 3 期研究的規模大致相當。一旦收集到第二階段研究數據，我們將分析並報告結果，屆時兩項第三階段研究將已經開始。我期待明年初就該計劃提供更具體的時間指導。

And now I'll turn it over to Mark for a financial update beginning on slide 18.

現在我將把它交給 Mark，以獲取從幻燈片 18 開始的財務更新。

Thank you, Liz. Let's review our quarterly financial performance on slide 19.

謝謝你，莉茲。讓我們回顧一下幻燈片 19 上的季度財務表現。

In the third quarter, we recorded $250.4 million in total net sales, up 18% from the third quarter of last year. DAYBUE net product sales were $91.2 million in the third quarter, up from $66.9 million in the third quarter of last year. Sequentially, DAYBUE sales were up 8% from the second quarter, comprised of 4% volume growth and 4% net price growth.

第三季度，我們的淨銷售額總額為 2.504 億美元，比去年第三季成長 18%。第三季 DAYBUE 產品淨銷售額為 9,120 萬美元，高於去年第三季的 6,690 萬美元。隨後，DAYBUE 銷售額較第二季成長 8%，其中銷量成長 4%，淨價成長 4%。

NUPLAZID net product sales were $159.2 million in the third quarter, up 10% versus the prior year's third quarter comprised of 7% volume growth and 3% net price growth. Gross to net for NUPLAZID was 24.9% in Q3.

NUPLAZID 第三季產品淨銷售額為 1.592 億美元，比去年第三季成長 10%，其中銷量成長 7%，淨價成長 3%。第三季 NUPLAZID 的毛淨比為 24.9%。

R&D expenses decreased to $66.6 million in the third quarter of 2024 from $157 million in the third quarter of 2023. The decrease in research and development expense was related to a reduction in business development expenses as we made the $100 million upfront payment to Neuren for ex-North American rights to trofinetide in Q3 of last year.

研發費用從 2023 年第三季的 1.57 億美元減少至 2024 年第三季的 6,660 萬美元。研發費用的減少與業務開發費用的減少有關，因為我們在去年第三季向 Neuren 預付了 1 億美元以獲得曲芬肽的前北美權利。

SG&A expenses increased to $133.3 million in the third quarter of 2024 from $97.9 million in Q3 2023. The increase was mainly due to the ongoing NUPLAZID consumer activation campaign as well as onetime costs related to our CEO transition. We ended the quarter with a cash balance of $565.3 million, which increased $64.4 million versus the prior quarter.

SG&A 費用從 2023 年第三季的 9,790 萬美元增至 2024 年第三季的 1.333 億美元。這一增長主要是由於正在進行的 NUPLAZID 消費者激活活動以及與我們執行長換屆相關的一次性成本。本季結束時，我們的現金餘額為 5.653 億美元，比上一季增加了 6,440 萬美元。

I also have an update to share on our rare pediatric disease priority review voucher. Yesterday, we entered into an agreement to sell the PRV for $150 million. We expect this transaction to close in the fourth quarter. And as a reminder, as part of our licensing agreement with Neuren for trofinetide, we will owe Neuren one-third of the net proceeds received from this transaction.

我還有關於罕見兒科疾病優先審查券的最新消息要分享。昨天，我們簽訂了一項協議，以 1.5 億美元的價格出售 PRV。我們預計這筆交易將於第四季完成。提醒一下，作為我們與 Neuren 就曲非奈肽許可協議的一部分，我們將欠 Neuren 從本次交易中獲得的淨收益的三分之一。

Please turn to slide 20 for a discussion of our latest 2024 financial guidance. For DAYBUE, based upon our third-quarter results and the dynamics Bren described, we are narrowing our guidance range for DAYBUE and now expect net sales of $340 million to $350 million.

請參閱投影片 20，以了解我們最新的 2024 年財務指引的討論。對於 DAYBUE，根據我們第三季的業績和 Bren 描述的動態，我們正在縮小 DAYBUE 的指導範圍，現在預計淨銷售額為 3.4 億美元至 3.5 億美元。

For NUPLAZID, we are narrowing our guidance range to the high end of our previous range and now expect net sales of $600 million to $610 million. As Bren said earlier, this guidance does not rely on a meaningful impact from our recently launched DTC campaigns, the benefit of which will largely be achieved in 2025.

對於 NUPLAZID，我們將指導範圍縮小到先前範圍的高端，目前預計淨銷售額為 6 億至 6.1 億美元。正如 Bren 之前所說，該指南並不依賴我們最近發起的 DTC 活動的有意義的影響，其好處將在 2025 年很大程度上實現。

We are also narrowing our full-year NUPLAZID gross to net guidance, and our new guidance range is 26% to 27%. On the expense side, based upon year-to-date results, we are reducing our R&D guidance to $280 million to $290 million and increasing SG&A guidance to $480 million to $495 million.

我們也縮小了 NUPLAZID 全年毛淨指引，新的指引範圍為 26% 至 27%。在費用方面，根據今年迄今的結果，我們將研發指導減少至 2.8 億至 2.9 億美元，並將銷售、管理和行政費用指導增加至 4.8 億至 4.95 億美元。

Lastly, we are raising our cash guidance range to $600 million to $640 million, reflecting our expectations for our operational performance. This range does not reflect the anticipated net proceeds from our sale of our PRV.

最後，我們將現金指引範圍提高至 6 億至 6.4 億美元，反映了我們對營運績效的預期。該範圍並不反映我們出售 PRV 的預期淨收益。

And now I'll turn the call over to Catherine for closing remarks.

現在我將把電話轉給凱瑟琳做總結發言。

Let's now please turn to slide 21. As we head towards the end of the year, our business today is built on a strong foundation, and I am excited for us to drive further growth in 2025 and beyond. We will continue to execute on the significant opportunity that remains in front of us for both DAYBUE and NUPLAZID to drive that growth. We will also work diligently to enroll our two late-stage trials as well as our pipeline programs and potential for business development deals.

現在請翻到投影片 21。隨著年底的臨近，我們今天的業務建立在堅實的基礎上，我很高興我們能夠在 2025 年及以後推動進一步成長。我們將繼續抓住 DAYBUE 和 NUPLAZID 面前的重大機會來推動這一增長。我們還將努力開展兩項後期試驗以及我們的管道計劃和業務發展交易的潛力。

We're pleased to be generating sustainable and expanding cash flow from operations to fund future growth. As I stated upfront, I truly believe that the deeper I dive into the company, the more enthusiastic I am about ACADIA's incredible potential for future growth.

我們很高興能夠從營運中產生可持續且不斷擴大的現金流，為未來的成長提供資金。正如我之前所說，我堅信，我對公司的了解越深入，我對 ACADIA 未來發展的不可思議的潛力就越充滿熱情。

With that, I'll turn it over to the operator for our Q&A. Operator?

這樣，我會將其轉交給接線員進行問答。操作員？

(Operator Instructions) Gregory Renza, RBC Capital Markets.

（操作員指令）Gregory Renza，RBC 資本市場。

Great. Good afternoon, Catherine and ACADIA team. Congrats on the progress. Catherine, welcome aboard, and thanks for taking my questions.

偉大的。凱瑟琳和 ACADIA 團隊，下午好。祝賀取得的進展。凱瑟琳，歡迎加入，感謝您提出我的問題。

Maybe to start, maybe I'll refrain from asking a question about Ryan Reynolds, but could you give us some interesting color on the rationale and what you saw the attractiveness of joining ACADIA? Your mention of business development and certainly the early-stage pipeline, I'm sure, is of interest to us. Just wondering if you could just add a little more color about how break down the strategic framework. What the capabilities are for ACADIA to sort of welcome in some of those business development assets as well as really nominating and fleshing out the early-stage pipeline that was of interest to you?

也許首先，我可能不會問有關 Ryan Reynolds 的問題，但您能否給我們一些有趣的理由，以及您認為加入 ACADIA 的吸引力是什麼？我確信我們對您提到的業務發展以及早期管道感興趣。只是想知道您是否可以在如何分解戰略框架方面添加更多色彩。ACADIA 有哪些能力可以歡迎其中一些業務開發資產，並真正提名和充實您感興趣的早期管道？

Great. Thanks for the question, Greg. So yes, I'll ask Bren to talk about Ryan Reynolds at a more appropriate point. But I will focus on business development.

偉大的。謝謝你的提問，格雷格。所以，是的，我會請布倫在更合適的時候談論瑞恩·雷諾茲。但我會專注於業務發展。

So yes, in terms of the focus of growth for the company, I believe business development is going to play an important role in our future. As you know, it's played an important role up until now in our growth with the acquisition of trofinetide.

所以，是的，就公司成長的重點而言，我相信業務發展將在我們的未來發揮重要作用。如您所知，到目前為止，透過收購曲芬肽，它在我們的發展中發揮了重要作用。

And so as we think about the framework that you asked around, obviously, we have a very strong footprint in neuropsychiatry and continue to develop drugs in that area. And I believe that will be part of our future and possible additional business development areas.

因此，當我們考慮您詢問的框架時，顯然，我們在神經精神病學領域擁有非常強大的足跡，並繼續在該領域開發藥物。我相信這將成為我們未來和可能的其他業務發展領域的一部分。

Rare disease, we now have 1.5 years under our belt, strong, successful launch with DAYBUE and rare continues to be a strong focus for the company. Beyond that, I'm working with the team to discuss further areas of interest, and we'll be sharing that probably at a slightly later date.

罕見疾病，我們現在已經有 1.5 年的歷史了，與 DAYBUE 的強大、成功的推出和罕見疾病仍然是公司的重點關注點。除此之外，我正在與團隊合作討論更多感興趣的領域，我們可能會在稍後的日期分享。

But just to confirm that we are in a strong financial cash position as Mark has outlined. And we feel very strongly that we are in a great position to look at business development deals as they come forward in the next few months.

但這只是為了確認我們的財務現金狀況良好，正如馬克所概述的那樣。我們強烈感覺到，我們處於有利地位，可以在未來幾個月內考慮業務發展交易。

That's helpful. Thank you. And maybe a question for Brendan. Just on the latter part of 2024 with respect to DAYBUE. And as you think about coming into the holiday season and we reflect on some of the December to January to February patient visits and DAYBUE utilization from patients and families, now how should we be thinking about some of the patterns when it comes to us entering Thanksgiving and the December holiday season and how it relates to transitioning to 2025? Thanks again, guys, and congrats.

這很有幫助。謝謝。也許還有一個問題想問布倫丹。就在 2024 年下半年，關於 DAYBUE。當您考慮進入假期時，我們會反思 12 月至 1 月至 2 月的一些患者就診以及患者和家屬對 DAYBUE 的使用情況，現在我們應該如何考慮進入感恩節時的一些模式12 月假期以及它與過渡到2025 年有何關係？再次感謝你們，恭喜你們。

Sure, Greg. Thanks so much for the question. Just as a reminder, this will be just our second first-quarter transition as we head into 2025. And a lot has changed in the DAYBUE franchise since then. First of all, we have a much better understanding of the reverification process and requirements for our patients. And we've built out those capabilities both within our hub, but also our family access manager team that's working very closely with each of our families during that transition.

當然，格雷格。非常感謝您的提問。提醒一下，這將是我們進入 2025 年時第二個第一季的過渡。從那時起，DAYBUE 系列發生了許多變化。首先，我們對重新驗證過程和患者的要求有了更好的了解。我們不僅在我們的中心內建立了這些功能，而且還在我們的家庭訪問管理團隊中建立了這些功能，他們在過渡期間與我們的每個家庭密切合作。

I think a very important difference is our patient mix heading into 2025, which is quite different than the mix we had in the first quarter of 2024. As I mentioned in our prepared remarks, we have over 60% of our current DAYBUE patients currently on treatment for 10 months or longer, which obviously wasn't even possible in the first quarter of 2024.

我認為一個非常重要的區別是我們進入 2025 年的患者組合，這與我們在 2024 年第一季的組合有很大不同。正如我在準備好的發言中提到的，我們目前有超過 60% 的 DAYBUE 患者正在接受 10 個月或更長時間的治療，這在 2024 年第一季顯然是不可能的。

There were far less than 10% of patients at that time that had been on therapy that long. So I think that provides a much more dependable base of business for first-quarter demand.

當時接受治療時間這麼長的患者遠低於 10%。因此，我認為這為第一季的需求提供了更可靠的業務基礎。

In terms of patient dynamics, I would think that just as we've seen in Parkinson's disease, I don't think that patients tend to schedule as many appointments in January. So that wouldn't be a surprise to me. But otherwise, we fully expect to grow patients and sales in 2025 over the longer period.

就患者動態而言，我認為就像我們在帕金森氏症中看到的那樣，我認為患者不會在一月安排那麼多的預約。所以這對我來說並不奇怪。但除此之外，我們完全預期 2025 年患者數量和銷售額將在較長時期內成長。

Fantastic. Thanks so much.

極好的。非常感謝。

Jason Butler, Citizens.

傑森·巴特勒，公民。

Hi. Thanks for taking the questions and congrats on the quarter. I guess just a couple on NUPLAZID. Can you give us a sense of the profile of patients that are initiating therapy now in the context of the branded and unbranded campaigns? I guess -- and also in terms of the label change.

你好。感謝您提出問題並祝賀本季。我猜 NUPLAZID 上只有幾個。您能否讓我們了解一下在品牌和非品牌活動背景下正在開始治療的患者的概況？我想——而且在標籤變化方面也是如此。

Are you seeing more older patients initiated on therapy versus -- to what extent are you seeing patients come on board earlier in the diagnosis or early in the psychosis symptoms?

您是否看到更多老年患者開始接受治療，而您看到患者在診斷早期或精神病症狀早期接受治療的程度如何？

Yeah. Thanks for the question, Jason. I'm going to let Brian answer that for us.

是的。謝謝你的提問，傑森。我會讓布萊恩為我們回答這個問題。

Thanks, Jason, for the question. I would say first, we're in very early days post launch of both of those campaigns. But I can tell you from what we're seeing for patient dynamics thus far, the mix of prescribers still seems to reflect what we see from what we saw in the second and third quarter. So we're seeing the same kind of prescribers that are our targets and a similar number of new physicians that are new to the brand.

謝謝傑森的提問。我首先要說的是，我們正處於這兩項活動啟動後的早期階段。但我可以告訴你，從迄今為止我們所看到的患者動態來看，處方醫生的組合似乎仍然反映了我們在第二季和第三季看到的情況。因此，我們看到同樣類型的處方者是我們的目標，以及類似數量的新醫生是品牌的新人。

In terms of the age of our patients, it's been largely what we would expect. I think the caregiver campaign has helped to help connect families to identify perhaps more readily subtle changes that they're seeing in their loved ones. But I don't think we've seen a substantial change in the age of our patients so far.

就我們患者的年齡而言，這很大程度符合我們的預期。我認為照顧者活動有助於幫助家庭建立聯繫，以識別他們在親人身上看到的也許更容易的微妙變化。但我認為到目前為止我們還沒有看到患者年齡的實質變化。

Okay, great. Thanks for taking the question.

好的，太好了。感謝您提出問題。

Ami Fadia, Needham & Company.

阿米法迪亞 (Ami Fadia)，李約瑟公司。

Hi, this is Puna on for Ami. Thank you for taking our question. You've suggested that you'll be having $1 billion in sales in 2025. Just wondering are you anticipating any decline in DAYBUE sales relative to 2024? What is the mix of the two products? Thank you.

大家好，我是 Ami 的 Puna。感謝您提出我們的問題。您曾表示，到 2025 年，您的銷售額將達到 10 億美元。只是想知道您預計 DAYBUE 銷售額相對 2024 年是否會下降？這兩種產品的組合是什麼？謝謝。

Thanks, Puna. I'm going to let Mark answer that for us.

謝謝，普納。我會讓馬克為我們回答這個問題。

So let me just clarify that. Thanks for the question. I think what we're saying is, right now, we have $250 million in sales in the quarter, and that equates to a run rate of $1 billion. So we're not, at this point, guiding yet for the full year 2025. But we're pleased to kind of have a run rate milestone that's over $1 billion, and then we'll guide into next year. But certainly, at this time, can share that we expect growth in both franchises and growth over that in 2025.

讓我澄清一下。謝謝你的提問。我認為我們所說的是，目前我們本季的銷售額為 2.5 億美元，相當於 10 億美元的運行率。因此，目前我們還沒有為 2025 年全年提供指導。但我們很高興能夠實現超過 10 億美元的運行率里程碑，然後我們將進入明年。但現在可以肯定的是，我們預計特許經營權和 2025 年都會成長。

Marc Goodman, Leerink Partners.

馬克古德曼，Leerink Partners。

Hi, this is Basma on for Mark. We have a question regarding DAYBUE. Regarding the 50% or 60% of the patients remaining on therapy. Do we know the proportion of patients who respond to the treatment and actually demonstrate clinical benefits? Should we assume that all of them at this point are responders and basically benefit from the therapy?

大家好，我是巴斯瑪，為馬克代言。我們有一個關於 DAYBUE 的問題。關於 50% 或 60% 的患者仍在接受治療。我們是否知道對治療有反應並實際表現出臨床益處的患者比例？我們是否應該假設此時所有人都是反應者並且基本上從治療中受益？

And on the flip side, I wonder if you could provide us with more color on the discontinuation data and share with us what is the key factor that really drives the discontinuation of therapy? Is it the A profile or is it the lack of treatment effect? Thank you.

另一方面，我想知道您是否可以為我們提供更多有關停藥數據的信息，並與我們分享真正推動治療停藥的關鍵因素是什麼？是A型還是治療效果不足？謝謝。

Thank you, Basma. I think I'm going to ask Bren to take us through those two questions.

謝謝你，巴斯瑪。我想我要請布倫帶我們解決這兩個問題。

Sure. No problem. And thank you for the question. First, just to confirm, yes, we have over 60% of patients at 10 months or longer. And what we see there is the flattening of the persistency curve out to 15 months for the latest cohort that we're looking at, which is very encouraging.

當然。沒問題。謝謝你的提問。首先，我想確認一下，是的，我們有超過 60% 的患者處於 10 個月或更長時間。我們看到，我們正在研究的最新隊列的持久性曲線已趨於​​平坦，達到 15 個月，這是非常令人鼓舞的。

What that would suggest to us is that patients have worked through the treatment journey and have found the dose that they're settling in on and are benefiting. Our family access manager team and our clinical nurses at the hub would confirm that these patients are benefiting and continuing. So I think that answers that question.

這對我們來說意味著患者已經完成了治療過程，並找到了他們正在接受的劑量並且正在受益。我們的家庭訪問經理團隊和中心的臨床護理師將確認這些患者正在受益並持續受益。所以我認為這回答了這個問題。

The second question around discontinuations, we still see that the majority of discontinuations happen in the first one or two fills of treatment. And that is consistent in terms of the reasons for discontinuation; tends to be diarrhea or vomiting and not so much a lack of treatment effect. It's really the tolerability in the early fills.

關於停藥的第二個問題，我們仍然看到大多數停藥發生在第一次或兩次治療。這與停止的原因是一致的；往往是腹瀉或嘔吐，並不是缺乏治療效果。這確實是早期填充的耐受性。

Thanks, Bren.

謝謝，布倫。

Tess Romero, JPMorgan.

苔絲‧羅梅羅，摩根大通。

Hi, team. This is Caroline Pocher on for Tessa Romero with JPMorgan. Thanks for taking our questions. So first, in your prepared remarks, you had mentioned that the DAYBUE launch is now at steady state of new patient flow. We were just curious if you could just clarify this statement. Does this mean steady net adds?

大家好。我是摩根大通的卡洛琳·波徹 (Caroline Pocher) 代表泰莎·羅梅羅 (Tessa Romero)。感謝您回答我們的問題。首先，在您準備好的發言中，您提到 DAYBUE 的推出目前處於新病患流量的穩定狀態。我們只是好奇您能否澄清這個說法。這是否意味著淨增量穩定？

And then you mentioned it will be a focus to grow this over the next few quarters. Is there anything that has fundamentally changed in your strategy to accelerate new patient starts? And are you considering changing or pivoting any facets of the launch strategy going forward? Thank you.

然後您提到這將是未來幾季發展的重點。您加速新患者啟動的策略是否發生了根本性改變？您是否正在考慮改變或調整未來發布策略的任何方面？謝謝。

Thanks, Caroline. I'll take some of that in terms of the perspectives that I've developed with the team over the last six weeks. So just to go back to the original part of the question. In terms of the steady state, yes, we're seeing a steady state of patient adds after a very strong start to the DAYBUE launch. And that's not unusual in rare disease launches.

謝謝，卡洛琳。我將根據過去六週我與團隊一起發展的觀點來考慮其中的一些觀點。所以回到問題的原始部分。就穩定狀態而言，是的，在 DAYBUE 推出的強勁開局之後，我們看到了患者數量的穩定狀態。這在罕見疾病的上市中並不罕見。

As you know, you see a big burst of patients out the door with the high unmet medical need and then tend to sort of go to a more plateaued phase. But we are looking to see how we can recharge that growth and start to see more patients coming in the top of the funnel. And we believe that there is a strong possibility of driving that growth.

如您所知，您會看到大量患者因醫療需求未滿足而大量湧出，然後往往會進入一個更穩定的階段。但我們正在尋找如何為這種成長注入新動力，並開始看到更多的患者進入漏斗頂部。我們相信推動這種成長的可能性很高。

And let me just tell you what the areas that we're focusing on in order to achieve that. The first is efficacy. What we've learned over the last six quarters is that the scales that we use in our clinical trials, the RSBQ and the CGI-I, they need to be brought to life for physicians. And they need to understand for their patients the impact that DAYBUE can promise them for their changes in cognition, their changes in communication, their changes in handwringing.

讓我告訴您為了實現這一目標，我們將重點放在哪些領域。首先是功效。過去六個季度我們了解到，我們在臨床試驗中使用的量表 RSBQ 和 CGI​​-I 需要為醫生提供實際應用。他們需要了解 DAYBUE 可以為患者帶來的認知變化、溝通變化、緊張情緒變化帶來的影響。

So bringing the efficacy to life is our first real focus as well as starting to enhance the data that we're generating around the LOTUS study and ensure we're amplifying this message to physicians and helping them understand the longer-term impact of DAYBUE on their patients.

因此，將功效變為現實是我們第一個真正關注的焦點，同時開始增強我們圍繞 LOTUS 研究生成的數據，並確保我們向醫生傳達這一信息，幫助他們了解 DAYBUE 對患者的長期影響。病人。

The second, Bren has just sort of mentioned, which is managing the patient journey. With all rare diseases, we need to really start thinking about the patient journey that surrounds the patient when they start on therapy and as they continue to persist.

布倫剛剛提到了第二個，即管理患者的旅程。對於所有罕見疾病，我們需要真正開始思考患者開始接受治療以及繼續堅持治療時所經歷的患者歷程。

And as Bren has indicated, we're really going to start focusing on those first few fells to ensure that patients are guided through that first process. But also, we now have a strong mature cohort of patients towards the end of the treatment, right out beyond 15 months now and ensuring that our families are supported throughout that whole journey.

正如布倫所指出的，我們確實將開始關注最初的一些問題，以確保引導患者完成第一個過程。而且，我們現在在治療即將結束時擁有一群強大的成熟患者，現在已經超過 15 個月了，並確保我們的家人在整個治療過程中得到支持。

And then finally, we've talked about the penetration of DAYBUE into the currently diagnosed patient population of 30%. A couple of things. First of all, we've seen the diagnosis rate increase since the launch of DAYBUE. We've seen that increase by around 10%, which obviously allows us to go after more patients and make them aware of the opportunities with DAYBUE.

最後，我們討論了 DAYBUE 在目前診斷患者群體中的滲透率為 30%。有幾件事。首先，自從 DAYBUE 推出以來，我們看到診斷率有所提高。我們看到這一數字增加了 10% 左右，這顯然使我們能夠追蹤更多患者，並讓他們意識到 DAYBUE 的機會。

And secondly, 70% of our patients are treated outside our COEs. So we see a strong opportunity for growth outside of our centers of excellence. So if I compound those three factors, enhancing the efficacy, really focusing on the patient journey at the beginning, and then driving the growth beyond our COEs, I feel very strongly that we will see strong DAYBUE growth as we move into 2025.

其次，我們 70% 的患者在我們的 COE 之外接受治療。因此，我們看到了卓越中心以外的巨大發展機會。因此，如果我將這三個因素結合起來，提高療效，從一開始就真正關注患者的旅程，然後推動超出我們COE 的增長，我強烈地感覺到，進入2025 年，我們將看到DAYBUE 的強勁增長。

Great. Thank you so much.

偉大的。太感謝了。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi. Thanks for taking the question. What do you think of the ratio of the patients on therapy to the number of unique prescribers? And I guess what I mean is that looks like there's been about 1,500 patients who have started therapy at some point with about 800 unique prescribers. So that's a little bit less than two patients per prescriber and perhaps I would have expected it to be a little bit more concentrated.

你好。感謝您提出問題。您如何看待接受治療的患者與獨特處方者數量的比例？我想我的意思是，看起來大約有 1,500 名患者在某個時候開始接受大約 800 名獨特處方者的治療。因此，每個處方者的治療量略少於兩名患者，也許我本來期望它會更加集中一些。

Thanks, Joe. That's a great observation and one that I know we've been looking at. So Bren, do you want to share a little bit more about that?

謝謝，喬。這是一項很棒的觀察，我知道我們一直在關注這個觀察。那麼布倫，你想分享更多一點嗎？

For sure. Joel, thanks for the question. And I think it's right. There is a concentration and a long tail. And I think for a first mover in a rare disease area, the centers of excellence still have the vast majority of prescribers that have multiple referrals that are written for DAYBUE.

一定。喬爾，謝謝你的提問。我認為這是對的。有集中，有長尾。我認為，對於罕見疾病領域的先驅來說，卓越中心仍然擁有絕大多數處方者，他們擁有針對 DAYBUE 撰寫的多個轉介。

High-volume institutions also have a concentration of physicians that have three or more referrals that have been written and we're continuing to penetrate those. In the community, as we've gone further and further into the community, it is not uncommon to see a physician that may have one patient or one or two patients that they see less frequently.

高容量機構也集中了擁有三份或更多已撰寫轉介的醫生，我們正在繼續滲透這些內容。在社區中，隨著我們越來越深入社區，看到一個醫生可能有一個病人或一兩個他們不常看的病人的情況並不少見。

And there, you see kind of a long tail of not necessarily pediatric neurologists anymore; you're seeing primary care physicians and some pediatricians who likely will have one patient to offer. We are, however, focused on those physicians that have written one or two prescriptions for DAYBUE, and we know they have additional patients for follow-up.

在那裡，你會看到一條長尾，不一定是兒科神經科醫生；您正在看初級保健醫生和一些兒科醫生，他們可能會為一名患者提供服務。然而，我們關注的是那些開過一兩個 DAYBUE 處方的醫生，我們知道他們還有其他患者需要追蹤。

Thank you.

謝謝。

Keith Tapper, BMO Capital Markets.

Keith Tapper，BMO 資本市場。

Thanks, and good afternoon, team. And thanks for taking my question. Welcome and congratulations to Catherine. Obviously, a [benefit] for ACADIA. So for DAYBUE, could you remind us what to expect from the Canadian approval maybe in '25 and '26 in terms of launch expenses, material impact to revenues if all goes well? And then, have you guided for time lapse revenues in Europe and Japan?

謝謝，團隊下午好。感謝您提出我的問題。歡迎並祝賀凱瑟琳。顯然，這對 ACADIA 來說是[好處]。那麼對於 DAYBUE，您能否提醒我們，如果一切順利的話，加拿大可能會在 25 年和 26 年批准對發射費用以及對收入的重大影響方面的預期？那麼，您對歐洲和日本的縮時攝影收入有指導嗎？

And then separately, I know it's early, but could you talk about 2591, which you have rights to in Fragile X? Is it a similar strategy versus DAYBUE, the drug itself? I know your partner Neuren showed interesting data, obviously in different indications. Anything you can share would be helpful there. Thank you.

然後分別來說，我知道現在還早，但你能談談你在《Fragile X》中擁有的權利2591嗎？它與 DAYBUE（藥物本身）是否有類似的策略？我知道你的合作夥伴 Neuren 展示了有趣的數據，顯然是在不同的適應症中。您可以分享的任何內容都會有幫助。謝謝。

Thanks, Keith. I'm going to ask Bren to elaborate a little bit more about our strategy in Canada, Europe, and Japan, and then will Liz perhaps take the 2591 question. So Bren.

謝謝，基斯。我將請 Bren 詳細說明我們在加拿大、歐洲和日本的策略，然後 Liz 可能會回答 2591 問題。所以布倫.

For sure. Thanks. We're obviously excited to have an ex-US approval for Canada. Very much looking forward to serving that patient population. Post approval, we then enter into negotiations with health technology assessment approvals.

一定。謝謝。我們顯然很高興獲得加拿大的前美國批准。非常期待為該患者群體提供服務。批准後，我們將與衛生技術評估批准進行談判。

We're going to be talking with the stakeholders about public and private reimbursement. We anticipate having limited coverage in 2025 through private payers and the public payer process tends to take a bit longer.

我們將與利害關係人討論公共和私人報銷問題。我們預計 2025 年私人付款人的承保範圍有限，而公共付款人流程往往需要更長的時間。

In the interim, we have a great opportunity to work with the centers that have Rett patients in Canada and begin to generate their interest in signing patients up for when we do have reimbursed approval. So we'll be doing that in the interim. And otherwise, we are very much looking forward to making DAYBUE accessible to patients as soon as we can, while we're actively engaging those necessary stakeholders to get to coverage.

在此期間，我們有一個很好的機會與加拿大有 Rett 患者的中心合作，並開始激發他們在我們獲得報銷批准後簽約患者的興趣。因此，我們將在此期間這樣做。除此之外，我們非常期待盡快讓患者能夠使用 DAYBUE，同時我們正在積極與那些必要的利害關係人接觸以實現覆蓋。

And to comment a little bit on 2591. I think I'll start out by commenting generally. We think we've got a first great treatment for patients living with Rett with DAYBUE but are obviously interested in continuing to find new ways to serve that community. So 2591 and other things that you may see come from us in the future really show our commitment to this patient population.

並對2591發表一點評論。我想我將從一般性評論開始。我們認為我們已經透過 DAYBUE 為 Rett 患者提供了第一個很好的治療方法，但顯然我們有興趣繼續尋找新的方法來服務該社區。因此，2591 以及您將來可能會看到的我們的其他產品真正體現了我們對這群患者的承諾。

At this point, it's probably premature to talk too specifically about what we're thinking about from a clinical perspective. I'll just generally say that we are learning from Neuren and their interesting data that they have compiled so far as well as putting together our own set of information that we think is necessary to have a Rett-specific strategy with this asset. So more that I'll be able to talk about in the future.

在這一點上，過於具體地談論我們從臨床角度思考的問題可能還為時過早。我只是籠統地說，我們正在向 Neuren 學習，學習他們迄今為止收集的有趣數據，並將我們自己的一組資訊放在一起，我們認為這些資訊對於針對該資產制定 Rett 特定策略是必要的。所以我以後可以談更多。

And just, Keith, in terms of Europe and Japan, we are preparing our MAA, as Liz has already referred to in the prepared remarks. We started to build out a team in Europe to support that launch, and we're looking forward to not only making our DAYBUE product available for patients in Canada but in Europe and beyond. And in terms of Japan, Liz alluded to, and it was on the slide, our discussions with the PDMA. So all of those discussions are currently active and ongoing.

基思，就歐洲和日本而言，我們正在準備我們的 MAA，正如莉茲在準備好的演講中所提到的那樣。我們開始在歐洲建立一個團隊來支援該產品的發布，我們期待不僅為加拿大的患者提供我們的 DAYBUE 產品，而且還為歐洲及其他地區的患者提供服務。就日本而言，莉茲在幻燈片上提到了我們與 PDMA 的討論。因此，所有這些討論目前都在積極進行中。

Tazeen Ahmad, Bank of America Securities.

塔津‧艾哈邁德，美國銀行證券公司。

Hi. Good afternoon. Thanks for taking my questions, and Catherine, a welcome from me as well. I wanted to get your thoughts about how to think about the European launch. In your previous role, you did handle ex-US launches. Are there certain rules of thumb to be aware of as it relates to rare disease launches in Europe that you can share with us today? And can you talk to us about your general plan forward in that region? Thanks.

你好。午安.感謝您提出我的問題，凱瑟琳也表示歡迎。我想了解一下您對歐洲發布的看法。在您之前的職位中，您確實負責過美國以外的發布。您今天可以與我們分享與在歐洲推出罕見疾病有關的某些經驗法則嗎？您能和我們談談您在該地區的整體計劃嗎？謝謝。

Sure. Thanks, Tazeen. So as I've just said, we are preparing for our MAA application early next year in Europe. As you know, there's a set time clock in Europe. It normally takes up to a year for that document to be assessed.

當然。謝謝，塔津。正如我剛才所說，我們正在準備明年初在歐洲的 MAA 申請。如您所知，歐洲有固定的時鐘。評估該文件通常需要一年的時間。

Then we start the clock with each of the national HTAs on reimbursement, and we would normally expect to launch in Germany first as well as Switzerland and then other company -- other countries come online after that, depending on how long our local negotiations take with both the national authorities and then some of the regional authorities in places like France, Italy, and Spain.

然後我們開始與每個國家 HTA 進行報銷，我們通常期望首先在德國以及瑞士啟動，然後是其他公司 - 其他國家隨後上線，具體取決於我們與當地的談判需要多長時間。義大利和西班牙等地的一些地區當局。

In terms of managing a rare disease launch in Europe, from my experience, it's a relatively similar to managing a rare disease launch in the US. Except that, in some ways, it's a little bit easier because with a single healthcare system in all of our countries in Europe, we have less involvement in the patient journey. The access to medicines once it's prescribed is a lot easier. We're not dealing with payers on a sort of a case-by-case basis.

就管理歐洲罕見疾病的上市而言，根據我的經驗，這與管理美國罕見疾病的上市相對相似。除此之外，在某些方面，這要容易一些，因為歐洲所有國家都有單一的醫療保健系統，我們對病患旅程的參與較少。一旦開立處方，獲得藥物就會容易得多。我們不會根據具體情況與付款人打交道。

And so while we need to wrap around support of the physician and patient, it just looks slightly different in terms of that individual patient journey. But with my experience and the team already being built up in Europe, I feel very confident that we will have DAYBUE available post registrational approval, and we're looking forward to making that launch successful as well.

因此，雖然我們需要圍繞著醫生和患者的支持，但就個別患者的旅程而言，它看起來略有不同。但憑藉我的經驗和在歐洲已經建立的團隊，我非常有信心我們將在註冊批准後推出 DAYBUE，我們也期待著該產品的發布取得成功。

Jeff Hung, Morgan Stanley.

傑夫洪，摩根士丹利。

Thanks for taking my questions. For ACP-204, just wondering if there's any updates on whether EU regulators have agreed to your master protocol? And can you just remind us of the strategy there? Thanks.

感謝您回答我的問題。對於 ACP-204，只是想知道歐盟監管機構是否同意您的主協議是否有任何更新？您能提醒我們一下那裡的策略嗎？謝謝。

Yes, I'll ask Liz to take that one for us.

是的，我會請莉茲幫我們拿一份。

Sure. So we haven't reengaged with them about the master protocol, the Phase 3 portions, in particular. We anticipate doing that when we're a little further into the Phase 2 portion of the study. That said, again, all this really means is that Europe may be a little bit slower up and running on the Phase 3 portion of the -- on the Phase 3 portions of the master protocol.

當然。因此，我們還沒有與他們重新討論主協議，特別是第三階段部分。我們預計當我們進一步進入研究的第二階段部分時就會這樣做。話雖如此，這一切真正意味著歐洲在主協議的第三階段部分上的啟動和運行可能會稍微慢一些。

But the advantage is that potentially we'd be in a position of starting up Phase 3 there with data in hand from the Phase 2 portion, which is really helpful in terms of getting investigator interest. So it's a little bit of a bump in the road, but we don't see this having an overall implication on strategy or timeline.

但好處是，我們可能能夠利用第二階段部分的資料啟動第三階段，這對於引起調查人員的興趣非常有幫助。因此，這在道路上有點坎坷，但我們認為這不會對策略或時間表產生整體影響。

Thank you.

謝謝。

Ritu Baral, TD Cowen.

裡圖·巴拉爾，TD·考恩。

Hey, guys. This is Athena on for Ritu. Thanks for taking my question. I had another follow-up on high-value academic centers and community practices. How should we think about forward adoption rates here? And how comfortable are these physicians when it comes to titrating DAYBUE? And what learnings are you applying from the earlier stages of DAYBUE's launch to your conversations with these folks? Thank you.

嘿，夥計們。這是雅典娜為 Ritu 配音的節目。感謝您提出我的問題。我對高價值學術中心和社區實踐進行了另一次跟進。我們該如何考慮這裡的遠期採用率？這些醫生在滴定 DAYBUE 時感覺如何？您將從 DAYBUE 推出的早期階段學到的哪些知識應用到與這些人的對話中？謝謝。

Thanks, Athena. I'll let Bren elaborate on that.

謝謝，雅典娜。我會讓布倫詳細說明這一點。

Yes, sure. Thank you for the question. As I think I alluded to in my prepared remarks, COEs were instrumental in the early part of the launch. And they still continue to contribute and we're driving further penetration there.

是的，當然。謝謝你的提問。正如我在準備好的演講中提到的那樣，COE 在發布的早期發揮了重要作用。他們仍在繼續做出貢獻，我們正在推動進一步滲透。

I'm pleased with what we've seen for high-volume institution penetration growth over the past year. I'm similarly pleased with our ability to get into the community to find those physicians that have Rett patients and see them continue to start to prescribe DAYBUE.

我對過去一年中機構滲透率的大幅成長感到滿意。我同樣對我們能夠進入社區找到那些治療 Rett 患者的醫生並看到他們繼續開始開 DAYBUE 處方感到高興。

The further you get from a COE, the more you're doing education on the particulars of Rett syndrome because they have infrequent visits with these patients as well as the clinical profile for DAYBUE. And we're starting to leverage those clinical champions, those that have a lot more experience with DAYBUE in the early part of the launch to do programs like discovery DAYBUE, where we'll pair a clinician and several caregivers that have had longer-term successful experiences on DAYBUE, to tell them what to expect in real-world performance of the product and what they're seeing in their loved ones. And that's been a very successful combination for us.

您從 COE 獲得的資訊越多，您對 Rett 症候群的詳細資訊進行的教育就越多，因為他們很少會見這些患者以及 DAYBUE 的臨床概況。我們開始利用那些在 DAYBUE 推出初期擁有更多經驗的臨床冠軍來開展諸如發現 DAYBUE 之類的項目，我們將在其中配對一名臨床醫生和幾名長期接受過 DAYBUE 治療的護理人員。經驗，告訴他們對產品的實際性能有何期望以及他們在親人身上看到了什麼。這對我們來說是一次非常成功的組合。

Thanks, Bren.

謝謝，布倫。

Paul Matteis, Stifel.

保羅馬蒂斯，斯蒂菲爾。

Hi. This is Julian on for Paul. Thanks so much for taking our question. Just a really quick one. What are your expectations for ROI on the DTC campaign in 2025 for NUPLAZID? Obviously, you've demonstrated strong execution in 2024. Just curious if you have any more commentary you can provide for next year. Thank you.

你好。這是保羅的朱利安。非常感謝您提出我們的問題。只是一個非常快的。您對 NUPLAZID 2025 年 DTC 活動的投資報酬率有何期望？顯然，您在 2024 年表現出了強大的執行力。只是好奇您是否可以為明年提供更多評論。謝謝。

Thanks. So Bren, do you want to talk about the direct-to-consumer campaign?

謝謝。那麼布倫，你想談談直接面向消費者的活動嗎？

For sure. And thanks for the question, Julian. So we initiated this campaign in the middle of August, and it's really just picked up its momentum as it relates to patient visits, starting to see their neurologists or movement disorder specialists.

一定。謝謝你的提問，朱利安。因此，我們在八月中旬發起了這項活動，它的勢頭確實剛剛好，因為它與患者就診有關，開始見他們的神經科醫生或運動障礙專家。

So we think the vast majority of the benefit we'll see -- will begin in 2025. But as a reminder, the lifetime value of our NUPLAZID patients, both in the community and long-term care will extend beyond 2025. So we'll start to see both an increase in new patient starts but also their continuing value throughout 2025, '26 and '27, perhaps beyond.

因此，我們認為我們將看到的絕大多數好處將於 2025 年開始。但需要提醒的是，我們的 NUPLAZID 患者的終身價值（無論是在社區還是長期照護中）都將延續到 2025 年之後。因此，我們將開始看到新患者數量的增加，以及它們在 2025 年、26 年和 27 年甚至更長時間內的持續價值。

And so I don't think we'll fully realize all of its value in '25. But we're enthusiastic about what we're seeing about early visits in some of the early returns.

所以我認為我們不會在 25 年完全實現它的所有價值。但我們對在一些早期回歸中看到的早期訪問感到興奮。

Thanks, Bren.

謝謝，布倫。

Charles Duncan, Cantor.

查爾斯鄧肯，康托爾。

Hey, good afternoon. Catherine and team, thanks for taking our question. And Catherine, congrats on the new opportunity with ACADIA. I had a quick question regarding ACP-204. In terms of the data release protocol, I guess I appreciate the master protocol in terms of facilitating enrollment, but I'm a little bit confused as to whether or not you'll be releasing any information from Phase 2 in terms of efficacy, et cetera, as the enrollment of the Phase 3s are ongoing. So please provide a little color there. Thanks.

嘿，下午好。凱瑟琳和團隊，感謝您提出我們的問題。凱瑟琳，恭喜您獲得 ACADIA 的新機會。我有一個關於 ACP-204 的快速問題。就資料發布協議而言，我想我很欣賞主協議在促進註冊方面的作用，但我對你們是否會在功效等方面發布第二階段的任何信息感到有點困惑等等，因為第三階段的註冊正在進行中。所以請在那裡提供一點顏色。謝謝。

Thanks for the question, Charles. I'm going to let Liz enhance that.

謝謝你的提問，查爾斯。我會讓莉茲加強這一點。

Yeah. Our current expectation is that we would be releasing some data at an appropriate time. And the expectation was always that we could use the Phase 2 data to make modifications to Phase 3 as needed.

是的。我們目前的期望是我們會在適當的時間發布一些數據。我們始終期望我們可以使用第 2 階段的資料根據需要對第 3 階段進行修改。

Jay Olson, Oppenheimer.

傑·奧爾森，奧本海默。

Thank you for providing the update and thanks for taking our question. For Catherine, could you please talk about your due diligence and any key considerations that you were contemplating as you considered taking on the role of CEO at ACADIA? And then also, maybe elaborate on your longer-term vision for ACADIA. Where would you like to see this company go in the future?

感謝您提供更新並感謝您提出我們的問題。Catherine，您能否談談您的盡職調查以及您在考慮擔任 ACADIA 執行長時考慮的任何關鍵考慮因素？然後，也許可以詳細說明您對 ACADIA 的長期願景。您希望這家公司未來走向何方？

Thank you, Jay. So in terms of the approach I had to looking at an opportunity, I was really looking for the combination of three things. First was a strong commercial base where I could come in and add value based on my experiences, 30 years so far, in the commercial side of the pharma business. And that's what I found with NUPLAZID and DAYBUE, very exciting core brands that we can look to grow and develop over the coming years.

謝謝你，傑伊。因此，就我尋找機會的方法而言，我實際上是在尋找三件事的結合。首先是一個強大的商業基礎，我可以根據我迄今為止 30 年在製藥業務商業方面的經驗加入並增加價值。這就是我對 NUPLAZID 和 DAYBUE 的發現，這兩個非常令人興奮的核心品牌，我們可以在未來幾年內持續成長和發展。

The second important area I was looking at was the pipeline, and that I was really excited by, and especially with our two later-stage clinical trials in Prader-Willi and Alzheimer's disease psychosis. And as I got into the due diligence, I was able to see a little bit more in the pipeline. I'm still very excited by that.

我關注的第二個重要領域是管道，我對此感到非常興奮，尤其是我們在普瑞德威利和阿茲海默症精神病方面的兩項後期臨床試驗。當我進行盡職調查時，我能夠看到更多的資訊。我對此仍然非常興奮。

And then finally, it was really around a strong financial position, which obviously ACADIA has and in terms of the cash position, but also a really strong Board and strong investors. And so those three things together made ACADIA for me a very attractive and exciting option.

最後，這確實是圍繞著強大的財務狀況，顯然 ACADIA 擁有，就現金狀況而言，而且還有一個非常強大的董事會和強大的投資者。因此，這三件事加在一起使阿卡迪亞對我來說成為一個非常有吸引力和令人興奮的選擇。

And I can tell you, six weeks in, I'm even more motivated and excited than I was when I first walked in the door here in San Diego. I'm very excited about the future and really believe that this company has only to go from strength to strength.

我可以告訴你，六週後，我比第一次走進聖地牙哥的大門時更有動力和興奮。我對未來感到非常興奮，並堅信這家公司只會不斷壯大。

Sumant Kulkarni, Canaccord.

蘇曼特·庫爾卡尼，Canaccord。

Good afternoon. Thanks for taking our question. Another one on DAYBUE. Other than patients being at centers of excellence versus not, what's your understanding of the key bottleneck that may be preventing new patients from starting DAYBUE? And what's the main variable you need to focus on to see an inflection on DAYBUE sales from current levels?

午安.感謝您提出我們的問題。DAYBUE 上的另一張。除了是否在卓越中心的患者之外，您對可能阻止新患者開始 DAYBUE 的關鍵瓶頸有何理解？您需要關注哪些主要變數才能看到 DAYBUE 銷售額相對於當前水準的變化？

Thanks, Sumant. Very fair question. So I'm going to let Bren answer that.

謝謝，蘇曼特。非常公平的問題。所以我要讓布倫來回答這個問題。

Hey, Sumant. Thanks so much for the question. I think we're focused entirely -- once you get beyond centers of excellence and some of the academic centers that are very much like COEs on education on the efficacy in the real-world setting. And so it really is a combination of focusing on physicians and explaining to them what the translation of CGI-I, RSBQ into daily improvements that families are seeing, which we're doing through a combination of peer-to-peer programming as well as having caregivers that have had their loved ones on therapy for two or three years, talk about what they've been able to see in their loved ones over time.

嘿，蘇曼特。非常感謝您的提問。我認為我們完全專注於——一旦你超越了卓越中心和一些非常類似於 COE 的學術中心，這些中心就現實世界環境中的功效進行教育。因此，這實際上是專注於醫生並向他們解釋 CGI-I、RSBQ 轉化為家庭所看到的日常改進的結合，我們正在通過點對點編程以及讓那些已經讓親人接受治療兩到三年的護理人員談論他們隨著時間的推移在親人身上看到的東西。

And then similarly, leveraging those experiences to speak to caregivers that may be on the sidelines, need to know more about what they should expect in their loved one. And we have a number of programs that look at patients between the ages of 2 and 5, 5 to 10, preteens, teenagers, and patients over the age of 20, so that we can really speak the language of the caregivers from similar experiences that some of the caregivers that have already started DAYBUE are well ahead on. And those are really our two primary areas of focus to elucidate efficacy and what I can see for clinical benefit for both of those audiences.

同樣，利用這些經驗與可能在一旁的護理人員交談，需要更多地了解他們對親人的期望。我們有許多計畫針對 2 至 5 歲、5 至 10 歲、青春期前的患者、青少年以及 20 歲以上的患者，以便我們能夠真正說出具有類似經歷的護理人員的語言，一些已經開始DAYBUE 的護理人員已經遙遙領先。這些確實是我們重點關注的兩個領域，旨在闡明功效以及我所看到的對這兩個受眾的臨床益處。

Danielle Brill, Raymond James.

丹妮爾·布里爾，雷蒙德·詹姆斯。

Hey, guys. This is Alex on for Danielle. Thanks for taking the question. Continuation on that -- on DAYBUE patient numbers, just curious what your level of effort is to potentially getting patients who have tried DAYBUE and discontinue to potentially back on treatment, given the ongoing learnings from real-world mitigation strategies to the adverse events? Thanks.

嘿，夥計們。這是亞歷克斯為丹妮爾代言。感謝您提出問題。繼續說下去——關於DAYBUE 患者數量，考慮到從現實世界的不良事件緩解策略中不斷學到的知識，您只是想知道，為了讓已經嘗試過DAYBUE 的患者停止可能重新接受治療，您的努力程度是多少？謝謝。

Yes. Great. Thank you. Alex, I'll let Bren do that one as well.

是的。偉大的。謝謝。亞歷克斯，我也會讓布倫做這件事。

For sure. Great question. it's important to realize that we stay in contact with every family. And as you know and probably are pointing out here, there are some patients that will discontinue after just one or two fills mostly due to tolerability challenges.

一定。很好的問題。重要的是要意識到我們與每個家庭都保持聯繫。正如您所知並可能在這裡指出的那樣，有些患者在服用一兩次後就會停止服用，主要是由於耐受性方面的挑戰。

With those families, we're obviously checking to see what their GI management experience was like and looking to further educate them on strategies, both around GI tolerability and engaging their HCPs to make sure they have a strategy in place. But also understanding more about their dosing and treatment journey because there could be alternate approaches where they could work themselves to a dose that would be more effective.

對於這些家庭，我們顯然正在檢查他們的 GI 管理經驗如何，並希望進一步教育他們有關策略的教育，包括圍繞 GI 耐受性和讓他們的 HCP 參與以確保他們制定適當的策略。但也要更了解他們的劑量和治療過程，因為可能有其他方法可以讓他們自己調整到更有效的劑量。

And so that will certainly be something we continue to focus on over time. Up to now, I would say that the -- for restarts in terms of patients that have restarted, it's still significantly less than 10% of our overall patient base.

因此，隨著時間的推移，這肯定會是我們繼續關注的事情。到目前為止，我想說的是，就已重新開始治療的患者而言，它仍然遠低於我們整體患者基數的 10%。

Thanks, Bren.

謝謝，布倫。

And at this time, I would like to turn the call back over to Catherine Owen Adams for closing remarks.

此時，我想將電話轉回給凱瑟琳·歐文·亞當斯 (Catherine Owen Adams) 致閉幕詞。

Great. Thank you, operator. So thanks again, everyone, for joining us today. Really appreciate the welcome that you've given me into the ACADIA community. We look forward to updating you further on our progress in the next quarter.

偉大的。謝謝你，接線生。再次感謝大家今天加入我們。非常感謝您對我加入 ACADIA 社群的歡迎。我們期待向您進一步通報下一季的進展。

This does conclude today's call. Thank you so much for participating. You may now disconnect.

今天的電話會議到此結束。非常感謝您的參與。您現在可以斷開連線。