ACADIA Pharmaceuticals Inc (ACAD) 2024 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the ACADIA Pharmaceuticals conference call. My name is Shannon, and I will be your coordinator for today.

女士們、先生們，大家好，歡迎參加 ACADIA Pharmaceuticals 電話會議。我叫香農 (Shannon)，今天我將擔任你們的協調員。

I would now like to turn the presentation over to Al Kildani, Senior Vice President of Investor Relations and Corporate Communications at ACADIA. Please proceed.

現在，我想將演講交給 ACADIA 投資者關係和企業傳播資深副總裁 Al Kildani。請繼續。

Thank you. Good afternoon, and thank you for joining us on today's call to discuss ACADIA's fourth-quarter and full-year 2024 earnings. Joining me on the call today from ACADIA are Catherine Owen Adams, our Chief Executive Officer, who will provide some opening remarks; followed by Tom Garner, our Chief Commercial Officer, who will discuss our strong commercial brands, DAYBUE and NUPLAZID.

謝謝。下午好，感謝您參加今天的電話會議，討論 ACADIA 2024 年第四季和全年收益。今天，ACADIA 的執行長凱瑟琳·歐文·亞當斯 (Catherine Owen Adams) 將與我一起參加電話會議，並致開幕詞；接下來是我們的首席商務官湯姆·加納 (Tom Garner)，他將討論我們強大的商業品牌 DAYBUE 和 NUPLAZID。

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

今天與我們一起參加的還有執行副總裁兼研發主管 Elizabeth Thompson 博士，她將介紹我們的管道計劃的最新進展；以及我們的財務長 Mark Schneyer，他將回顧財務亮點。在我們開始回答大家的提問之前，凱瑟琳將會發表一些總結性發言。

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 be making several forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.

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，我們將根據 1995 年《私人證券訴訟改革法案》做出幾項前瞻性陳述。

These forward-looking statements, including goals, expectations, plans, prospects, growth potential, timing of events, future results, and 2025 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.

這些前瞻性陳述，包括目標、期望、計劃、前景、成長潛力、事件時間、未來結果和 2025 年財務指導，均基於當前資訊、假設和期望，這些資訊、假設和期望本質上可能會發生變化，並涉及可能導致結果發生重大差異的若干風險和不確定性。

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 unique 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的業務相關的其他風險可以在我們向美國證券交易委員會提交的文件中找到。請注意不要過度依賴這些前瞻性陳述，這些陳述僅代表今天的觀點。除非法律要求，我們不承擔隨著情況變化而更新或修改這些前瞻性聲明的義務。

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

現在我將把電話轉給凱瑟琳，請她致開幕詞。

Thank you, Al. Good afternoon, everyone, and thank you for joining us. Now five months into my role as CEO of ACADIA, I'm excited to share an update on the significant progress we have made. During our last call, my first with ACADIA, I expressed my enthusiasm for the company's strong foundation and the potential of our pipeline.

謝謝你，艾爾。大家下午好，感謝大家的參與。現在，我擔任 ACADIA 執行長已經五個月了，我很高興與大家分享我們所取得的重大進展。在我們最後一次通話中，也是我第一次與 ACADIA 通話時，我表達了對公司強大基礎和管道潛力的熱情。

Since then, the developments we've achieved have only reinforced my confidence in our future. These recent developments include delivering strong financial results in both commercial brands, as we will detail later in the call, with revenue guidance targeted at over $1 billion in the US in 2025, with volume growth for both brands; announcing new commercial leadership with Tom Garner joining ACADIA as our new Chief Commercial Officer; submitting our marketing application authorization with the European Medicines Agency for trofinetide, setting us up for our first approval outside North America; announcing a second indication we intend to study with ACP-204, Lewy Body Dementia Psychosis; adding to our pipeline an exciting new neuroscience program in ACP-711 for the treatment of essential tremor; providing greater transparency into the depth and diversity of our pipeline in both neuroscience and neuro-rare diseases by disclosing more details about our programs, culminating in our announcement of ACADIA's first R&D Day to be held on June 25; and further strengthening our balance sheet with the sale of our priority review voucher.

自從那時以來，我們所取得的發展更加增強了我對我們未來的信心。這些最新進展包括兩個商業品牌均取得強勁的財務業績，我們將在稍後的電話會議中詳細介紹，目標是到 2025 年在美國實現超過 10 億美元的收入，並且兩個品牌的銷量均實現增長；宣布新的商業領導層，湯姆·加納 (Tom Garner) 加入 ACADIA 擔任新任首席首席授權；宣布新的商業領導層，湯姆·加納 (Tom Garner) 加入 ACADIA 擔任新任首席執行官； ACP-204 研究的第二個適應症，即路易體癡呆症精神病；在我們的產品線中增加一項令人興奮的全新神經科學項目 ACP-711，用於治療特發性震顫；通過披露更多有關我們項目的細節，提高我們在神經科學和神經罕見疾病領域產品線的深度和多樣性的透明度，最終我們宣布 6 月 25 日舉行的首個資產票據和首個開券。

ACADIA's corporate strategy is anchored by our neuroscience and neuro-rare disease franchises. And we plan to deliver long-term growth by expanding these franchises, including exploring investments into additional adjacencies in rare disease. We also expect to execute some important value-creating milestones in 2025 and 2026, which I will detail later in the call.

ACADIA 的公司策略以我們的神經科學和神經罕見疾病特許經營權為基礎。我們計劃透過擴大這些特許經營權來實現長期成長，包括探索對罕見疾病其他鄰近領域的投資。我們也預計在 2025 年和 2026 年實現一些重要的價值創造里程碑，我將在稍後的電話會議中詳細介紹。

Now turning to our commercial highlights. Our commercial brands finished the year strong with record quarterly revenues and are both poised for volume and revenue growth in 2025. I'll begin with DAYBUE, which generated sales of $96.7 million in the fourth quarter, up 11% year over year and 6% sequentially. For the full year, DAYBUE sales were $348.4 million, up from $177.2 million in 2023, which was DAYBUE's launch year.

現在來談談我們的商業亮點。我們的商業品牌以創紀錄的季度收入強勢結束了這一年度，並預計在 2025 年實現銷售和收入的成長。我首先從 DAYBUE 開始，該公司第四季的銷售額為 9,670 萬美元，年增 11%，季增 6%。DAYBUE 全年銷售額為 3.484 億美元，高於 2023 年（DAYBUE 推出年份）的 1.772 億美元。

While our base of patients on therapy remains stable, we have continued confidence in the opportunity to grow this brand, both in the US and abroad. Tom will detail our key initiatives to accelerate patient and volume growth in the US, and our expectations for initial revenues from outside the US.

雖然我們接受治療的患者群體保持穩定，但我們仍然對在美國和國外發展該品牌的機會充滿信心。湯姆將詳細介紹我們加速美國患者和數量成長的關鍵舉措，以及我們對美國以外初始收入的期望。

Now turning to NUPLAZID, which generated sales of $162.9 million in the fourth quarter, up 13% year over year and full year sales of $609.4 million, up 11% from the prior year. We are very pleased with continued strength of NUPLAZID growth, driven primarily by volume as we begin to see the initial impact of our direct-to-consumer and unbranded campaigns, which were launched in mid-August of 2024. These efforts have boosted traffic to our disease awareness and NUPLAZID websites, sparking more patient -doctor discussions about Parkinson's-related hallucinations and delusions.

現在來看看 NUPLAZID，其第四季的銷售額為 1.629 億美元，年增 13%，全年銷售額為 6.094 億美元，年增 11%。我們對 NUPLAZID 持續強勁的成長感到非常高興，這主要得益於銷量，因為我們開始看到 2024 年 8 月中旬推出的直接面向消費者和非品牌活動的初步影響。這些努力增加了我們的疾病意識和 NUPLAZID 網站的訪問量，引發了更多患者與醫生之間關於帕金森氏症相關幻覺和妄想的討論。

Turning next to our pipeline. As I noted at the outset, ACADIA's robust pipeline was a key factor in my excitement to join the company. Last month, we introduced this slide at an investor conference, providing a more in-depth look at our diverse pipeline. I'd like to highlight a few key observations.

接下來轉向我們的管道。正如我在一開始所指出的，ACADIA 強大的管道是我興奮加入該公司的關鍵因素。上個月，我們在一次投資者會議上介紹了這張投影片，更深入地介紹了我們多樣化的產品線。我想強調幾點關鍵的觀察。

Our pipeline is significantly broader than was previously disclosed, with programs spanning neuroscience, rare disease, and areas where the two intersect. These product candidates cover all stages of development from discovery to Phase 3, leveraging a diverse range of unique mechanisms of action.

我們的研發管線比先前揭露的要廣泛得多，項目涵蓋神經科學、罕見疾病以及兩者交叉的領域。這些候選產品涵蓋了從發現到第 3 階段的所有開發階段，並利用了多種獨特的作用機制。

Furthermore, the indications we are pursuing align with our mission to bring new treatment options to underserved patient communities, while also representing substantial market opportunities with either first-in-class or potential best-in-class therapies in areas of high unmet medical need. We also look forward to sharing more information about our programs at our first-ever R&D Day, set for June 25 of this year in New York.

此外，我們所追求的適應症與我們的使命一致，即為服務不足的患者群體帶來新的治療選擇，同時也代表著在醫療需求高度未得到滿足的領域提供一流或潛在的最佳療法的巨大市場機會。我們也期待在今年 6 月 25 日於紐約舉行的首屆研發日上分享更多有關我們專案的資訊。

During the fourth quarter, we also strengthened our executive leadership, in particular, on the commercial side. I'd like to introduce Tom Garner, our new Chief Commercial Officer, who will provide additional color on the performance of our commercial brands.

在第四季度，我們也加強了行政領導力，特別是在商業方面。我想介紹我們的新任商務長湯姆·加納 (Tom Garner)，他將為我們的商業品牌的表現提供更多細節。

Tom joined us in December and has hit the ground running, already making a significant impact on our commercial organization. Having previously worked together successfully at Bristol Myers Squibb, I'm pleased to be collaborating with him once again.

湯姆於 12 月加入我們並立即開始工作，對我們的商業組織產生了重大影響。由於之前曾在百時美施貴寶公司成功合作過，我很高興能再次與他合作。

Thank you, Catherine. I'm truly excited to join ACADIA for many of the reasons that you've highlighted. To share a little about my background, I bring over 25 years of commercial experience, spanning both large pharma and biotech, including two decades at Bristol, where I led the US cardiovascular and established brands business unit, overseeing a portfolio exceeding $10 billion in revenue.

謝謝你，凱瑟琳。我真的很高興加入 ACADIA，原因有很多，正如您所強調的。分享我的背景，我擁有超過 25 年的商業經驗，涉及大型製藥和生物技術，其中包括在布里斯托爾工作的二十年，在那裡我領導美國心血管和成熟品牌業務部門，負責管理收入超過 100 億美元的投資組合。

This experience included leading rare disease launches, such as CAMZYOS, and large brands, such as ELIQUIS, which aligns well with my focus at ACADIA. Having successfully led and expanded commercial brands across a diverse range of therapeutic areas, I'm confident in the significant growth potential for both DAYBUE and NUPLAZID, both in the near and long term. As demonstrated in our strong Q4 results today, we are well positioned to continue driving momentum and delivering sustained growth for both brands.

這些經驗包括領導罕見疾病產品的發布，例如 CAMZYOS，以及大型品牌，例如 ELIQUIS，這與我在 ACADIA 的重點非常一致。憑藉著在多個治療領域成功領導和拓展商業品牌的經驗，我對 DAYBUE 和 NUPLAZID 在近期和長期內的巨大成長潛力充滿信心。正如我們今天強勁的第四季度業績所表明的那樣，我們已做好準備，繼續推動兩個品牌的發展，實現持續成長。

Let's begin with DAYBUE. We achieved record quarterly sales of $96.7 million in the fourth quarter, bringing us to $348.4 million for the year. Growth in the quarter was primarily driven by volume through increased bottle use per patient, as more stable patients titrated their doses upwards towards the recommended dose.

讓我們從 DAYBUE 開始。我們第四季的季度銷售額達到了創紀錄的 9,670 萬美元，全年銷售額達到 3.484 億美元。本季的成長主要得益於每位患者使用藥瓶數量的增加，因為病情更加穩定的患者將藥量逐漸增加至建議劑量。

We did see some expected year-end pull-forward, even excluding this dynamic. It was the third straight quarter of sequential bottle volume growth. During the quarter, 920 unique patients received paid shipments, which was essentially flat with the prior third quarter.

即使排除這種動態，我們確實看到了一些預期的年底提前。這是連續第三個季度瓶裝銷量成長。本季度，共有 920 名患者收到了付費發貨，與上一季基本持平。

An important factor for the future growth profile of DAYBUE is the fact that we have a stable and growing base of patients who remain on therapy long term, with over 62% of our current patients now having been on therapy for 12 months or longer. In Q4, this group of patients accounted for around 90% of the total DAYBUE volume.

DAYBUE 未來成長前景的一個重要因素是，我們擁有穩定且不斷增長的長期接受治療的患者群，目前超過 62% 的患者接受治療的時間已達 12 個月或更長時間。在第四季度，該組患者佔DAYBUE總量的90%左右。

Additionally, we observed a 15% quarter-over-quarter improvement in patient discontinuations. As we move forward, ongoing proactive support for Rett patients and their caregivers will remain an important element of our patient strategy to ensure individualized care for these considering or receiving DAYBUE.

此外，我們觀察到患者停藥率比上一季改善了 15%。隨著我們不斷前進，對 Rett 患者及其照護者的持續主動支持仍將是我們患者策略的重要組成部分，以確保為考慮或接受 DAYBUE 的患者提供個人化護理。

Overall, DAYBUE's persistency is impressive for a chronic rare disease, and I've observed many drugs with a considerably lower persistency at this point in the product launch cycle. As you see here, our overall persistency for patients on drug at 12 months remains at about 50%.

總體而言，對於一種慢性罕見疾病來說，DAYBUE 的持久性令人印象深刻，而且我觀察到在產品發布週期的這個階段，許多藥物的持久性都相當低。正如您所看到的，我們患者服藥 12 個月的整體堅持率仍保持在 50% 左右。

With regards to prescribers, we continue to broaden our prescriber base, with about 830 HCPs having prescribed DAYBUE, up from around 800 at the end of the third quarter. While pleased with the ongoing expansion of our HCP customer base, we believe there is still significant room for us to continue to broaden this as we aim to meet Rett patients wherever they may be in their specific journey. This will be an important component of our 2025 DAYBUE expansion strategy.

關於處方者，我們繼續擴大處方者基礎，目前約有 830 名 HCP 開出了 DAYBUE，高於第三季末的 800 名左右。雖然我們對 HCP 客戶群的不斷擴大感到高興，但我們相信，我們仍然有很大的拓展空間，因為我們的目標是滿足 Rett 患者的需求，無論他們處於特定的旅程中。這將是我們2025 DAYBUE擴張策略的重要組成部分。

Let's now review other strategic initiatives we are executing to further enhance and accelerate adoption. We strongly believe we have a meaningful opportunity to grow the DAYBUE brand, both in the US and beyond. Starting in the US, currently 35% of our patients are treated at Rett centers of excellence or COEs, with the remainder being treated at either high-volume institutions or community settings.

現在讓我們回顧一下我們正在執行的其他策略舉措，以進一步加強和加速採用。我們堅信，我們擁有在美國及其他國家發展 DAYBUE 品牌的重要機會。從美國開始，目前我們有 35% 的患者在 Rett 卓越中心或 COE 接受治療，其餘患者則在大型機構或社區環境中接受治療。

Over time, as we've noted, we expect to see more patients starting therapy outside of COEs, where the vast majority of Rett patients receive treatment. Today, our penetration for DAYBUE in these accounts is around 25% versus 55% for the centers of excellence, representing a significant growth opportunity.

正如我們所注意到的，隨著時間的推移，我們預計會看到更多患者在 COE 之外開始接受治療，而絕大多數 Rett 患者都在 COE 之外接受治療。如今，DAYBUE 在這些帳戶中的滲透率約為 25%，而卓越中心的滲透率則為 55%，這代表著巨大的成長機會。

With almost two years in the field, we now have a deeper and more nuanced understanding of the Rett patient journey and DAYBUE treatment dynamics and as a result, have identified additional opportunities to educate physicians outside of the centers of excellence about the benefits that DAYBUE offers.

經過近兩年在該領域的工作，我們現在對 Rett 患者的治療歷程和 DAYBUE 治療動態有了更深入、更細緻的了解，因此，我們找到了更多機會向卓越中心以外的醫生介紹 DAYBUE 所提供的益處。

To capitalize on these opportunities, we're significantly enhancing our ability to reach patients beyond the 21 centers of excellence. As we announced last month, we are expanding our field force by around 30% with a focus on increasing engagement with more treating HCPs and their patients.

為了利用這些機會，我們正在大力增強我們接觸 21 個卓越中心以外的患者的能力。正如我們上個月宣布的那樣，我們將把現場人員規模擴大約 30%，重點是增加與更多治療 HCP 及其患者的互動。

Most of these new roles will be demand generating, but we're also strengthening support for caregivers and patients throughout their treatment journey. Since launch, we've learned how crucial these support efforts are in helping caregivers and patients stay on therapy and in partnership with our HCPs, confidently adjust their dosage over time, which is an important driver of volume growth.

大多數新角色都是需求產生的，但我們也會加強對護理人員和病人整個治療過程中的支持。自推出以來，我們已經了解到這些支持工作對於幫助護理人員和患者堅持治療以及與我們的 HCP 合作、隨著時間的推移自信地調整劑量至關重要，這是銷量增長的重要驅動力。

Beyond the expansion of our customer model, we're also launching several key initiatives to drive growth and expand both our HCP and patient universe, including direct-to-consumer campaigns and new opportunities for peer-to-peer engagement, whether it be patient to patient, caregiver to caregiver, or HCPs sharing their experiences.

除了擴展我們的客戶模式之外，我們還推出了幾項關鍵舉措來推動成長並擴大我們的 HCP 和患者範圍，包括直接面向消費者的活動和點對點互動的新機會，無論是患者與患者之間、護理人員與護理人員之間，還是 HCP 之間分享他們的經驗。

Additionally, we continue to bring the DAYBUE data to life through omnichannel strategies, highlighting our clinical trial data and the real-world data from our LOTUS study. With these efforts, we're confident in our ability to build momentum and make a meaningful difference to the Rett community, where only about 30% of patients have even tried DAYBUE to date.

此外，我們繼續透過全通路策略將 DAYBUE 數據變為現實，重點是突出我們的臨床試驗數據和來自 LOTUS 研究的真實世界數據。透過這些努力，我們有信心能夠累積動力並為 Rett 社區帶來有意義的改變，迄今為止，只有約 30% 的患者嘗試過 DAYBUE。

We're also very excited to begin laying the foundation for the commercialization of DAYBUE outside of the US beginning this year. The opportunity in Europe is substantial, with an estimated 9,000 to 12,000 individuals affected by Rett syndrome.

我們也非常高興從今年開始為 DAYBUE 在美國以外的商業化奠定基礎。歐洲的機會巨大，估計有 9,000 至 12,000 人患有雷特氏症。

With the EMA approval anticipated in the first quarter of 2026, we've been actively building our EU launch team. And we will soon welcome a general manager for the region as well as a managing director in Germany, who will complement a highly experienced team we have already started building. These key talents will be focused on developing our market entry plans in 2025 and beyond.

由於預計 2026 年第一季將獲得 EMA 批准，我們一直在積極組建我們的歐盟發布團隊。我們很快就會迎來該地區的總經理和德國的董事總經理，他們將補充我們已經開始組建的經驗豐富的團隊。這些關鍵人才將專注於制定我們 2025 年及以後的市場進入計劃。

While caregivers and patients eagerly await approval, we're committed to making trofinetide available in certain European countries through managed access programs, subject to country-specific regulatory guidelines for those specific markets.

在護理人員和患者急切等待批准的同時，我們致力於透過管理訪問計劃在某些歐洲國家/地區提供曲菲奈肽，但須遵守針對這些特定市場的特定國家/地區監管指南。

Meanwhile, following last year's approval by Health Canada, we're on track for our first DAYBUE sales in Canada in the third quarter of this year. Additionally, we are fully evaluating our approach to making DAYBUE more widely available to Rett patients in select markets outside of the US, EU, and Canada. We are excited to record ACADIA's first revenues outside of the US later this year.

同時，繼去年獲得加拿大衛生部的批准後，我們預計將在今年第三季在加拿大首次銷售 DAYBUE。此外，我們正在全面評估我們的方法，以便讓美國、歐盟和加拿大以外的特定市場的 Rett 患者更廣泛地獲得 DAYBUE。我們很高興今年稍後 ACADIA 能在美國以外地區實現首次收入。

In summary, as we look at the outlook for DAYBUE in 2025, while we anticipate volume growth, the majority is expected to occur in the second half of the year as we expand our customer model and deploy new tactics to further broaden HCP engagement. We're continuing to actively engage with the Rett community through various channels according to their preferences.

總而言之，當我們展望 2025 年 DAYBUE 的前景時，雖然我們預計銷量會成長，但隨著我們擴大客戶模式並部署新策略以進一步擴大 HCP 參與度，預計大部分成長將發生在下半年。我們將繼續根據 Rett 社群的喜好，透過各種管道積極與他們互動。

Moving forward, we expect to see growth in both new patients and the number of unique patients receiving shipments. We anticipate maintaining stable persistency and increased utilization over time and are continuing to strengthen our tactics to support the growing number of stable patients on DAYBUE.

展望未來，我們預計新患者數量和接收貨物的獨立患者數量都會增加。我們期望隨著時間的推移保持穩定的持久性和增加的利用率，並將繼續加強我們的策略以支持 DAYBUE 上越來越多的穩定患者。

We expect to record revenues related to managed access programs and named patient programs in select countries outside the US. And we will continue to build upon the growing body of real-world evidence with DAYBUE, reinforcing its positive impact and value in the lives of Rett patients and their caregivers.

我們預計將在美國以外的特定國家記錄與管理訪問計劃和指定患者計劃相關的收入。我們將繼續利用 DAYBUE 不斷增長的真實世界證據，加強其對雷特氏症患者及其照護者的生活產生的正面影響和價值。

I'll now turn to NUPLAZID. NUPLAZID achieved fourth-quarter sales of $162.9 million, representing 13% revenue growth year over year. Overall, for the year, the brand grew top-line sales by 11%, which is the highest rate of annual sales growth since 2020, with total sales of $609.4 million.

現在我來談談 NUPLAZID。NUPLAZID 第四季銷售額達 1.629 億美元，年增 13%。總體而言，該品牌全年銷售額成長 11%，這是自 2020 年以來最高的年度銷售額成長率，總銷售額達到 6.094 億美元。

It's important to note that more than half of this growth or 6% is coming from volume. And this volume growth is happening across all market segments. Taken together, we believe that NUPLAZID has significant room to grow given the positive momentum we saw through the second half of 2024.

值得注意的是，這一增長中有一半以上（即 6%）來自銷售量。而且這種銷售成長正在所有細分市場發生。綜合來看，鑑於我們在 2024 年下半年看到的積極勢頭，我們相信 NUPLAZID 具有巨大的成長空間。

What I find most exciting about NUPLAZID sales performance is that we still only have about a 25% market share in those patients receiving atypical antipsychotics for the treatment of Parkinson's-related hallucinations and delusions. This is up from the 20% we have reported previously, meaning that we still have a tremendous opportunity to expand this share and continue growing the brand.

我發現 NUPLAZID 銷售表現最令人興奮的是，在接受非典型抗精神病藥物治療帕金森氏症相關幻覺和妄想的患者中，我們仍然只佔有約 25% 的市場份額。這比我們之前報告的 20% 有所上升，這意味著我們仍然有巨大的機會來擴大這一份額並繼續發展品牌。

Our key growth drivers in 2024 were the two key initiatives we have described as influencing HCP prescribing decisions over the past two years. One, leveraging the published real-world evidence showing an association of pimavanserin use compared with other atypical antipsychotics in important outcomes like all-cause mortality, 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.

我們 2024 年的主要成長動力是我們所描述的過去兩年影響 HCP 處方決策的兩項關鍵舉措。一是利用已發表的真實世界證據，證明與其他非典型抗精神病藥物相比，匹莫範色林的使用與全因死亡率等重要結果存在關聯，並向市場宣傳去年的標籤澄清，這有助於 HCP 了解他們可以治療出現幻覺和妄想（無論是否伴有共病癡呆症）的帕金森氏症患者。

Building on the momentum these initiatives created, starting in Q4, we also began to see the positive impact of both our branded awareness campaign and our branded campaign. Together, these initiatives drove increased traffic to our disease awareness and NUPLAZID websites, encouraging more conversations between patients and their doctors about the hallucinations and delusions associated with Parkinson's disease.

在這些舉措創造的勢頭的基礎上，從第四季度開始，我們也開始看到品牌知名度活動和品牌活動的正面影響。這些舉措共同增加了我們的疾病意識和 NUPLAZID 網站的訪問量，鼓勵患者和醫生之間就與帕金森氏症相關的幻覺和妄想進行更多對話。

Turning next to our commercial strategy and outlook for NUPLAZID. Our strategy to drive continued growth of NUPLAZID is straightforward. We want to continue activating and educating consumers and the HCP community about the clinical benefit that NUPLAZID offers through our highly impactful targeted DTC campaign and in-person sales efforts.

接下來談談我們對 NUPLAZID 的商業策略和展望。我們推動 NUPLAZID 持續成長的策略很簡單。我們希望透過極具影響力的定向 DTC 活動和麵對面銷售活動，繼續激勵和教育消費者和 HCP 社群了解 NUPLAZID 提供的臨床益處。

We want to drive market share gains against off-label generic antipsychotics by further leveraging real-world evidence to support prescriber decisions. And we're looking to maximize our field force efficiency with the use of predictive analytics and other analytical tools to be at the right place at the right time to educate about NUPLAZID.

我們希望透過進一步利用現實世界的證據來支持處方醫生的決策，從而推動非上市仿製抗精神病藥物的市場份額成長。我們希望利用預測分析和其他分析工具來最大限度地提高現場人員的效率，以便在正確的時間出現在正確的地點，對 NUPLAZID 進行宣傳教育。

As you will see in our 2025 sales guidance for NUPLAZID, our outlook is for continued sales growth, increasing market share and the publication of more real-world evidence data to support those goals, including five-year data, further highlighting the long-term value that NUPLAZID offers. In summary, we're excited to see the progress NUPLAZID is making and plan to build on that momentum through 2025.

正如您將在我們對 NUPLAZID 的 2025 年銷售指南中所看到的，我們預計銷售額將持續增長，市場份額將不斷增加，並將發布更多真實世界證據數據來支持這些目標，包括五年數據，從而進一步凸顯 NUPLAZID 提供的長期價值。總而言之，我們很高興看到 NUPLAZID 的進展，並計劃在 2025 年之前繼續保持這一勢頭。

I'll now turn it over to Liz.

現在我將把發言權交給 Liz。

Thanks, Tom. I'll begin with a brief regulatory update and then turn to our later-stage pipeline programs. We were pleased to start 2025 with our first European submission for marketing approval.

謝謝，湯姆。我將首先簡要介紹監管最新情況，然後再介紹我們的後期管道計劃。我們很高興在 2025 年開始首次向歐洲提交行銷批准申請。

As announced last month, we have now submitted our MAA for trofinetide in the EU. With this submission, we anticipate approval in the first quarter of 2026. In Japan, we continue productive discussions with PMDA about trofinetide and expect to begin a Phase 3 study in Japanese patients living with Rett syndrome in the third quarter of this year.

正如上個月宣布的那樣，我們現在已經向歐盟提交了曲菲奈肽的上市申請。透過此次提交，我們預計將於 2026 年第一季獲得批准。在日本，我們繼續與 PMDA 就曲菲奈肽進行富有成效的討論，並預計今年第三季度針對日本雷特症候群患者開始進行 3 期研究。

Now I'll comment briefly on our later-stage clinical programs as well as the recently licensed ACP-711. I'll start with our ACP-101 program in Prader-Willi syndrome. As a reminder, Prader-Willi is a rare genetic neurobehavioral disorder affecting roughly 8,000 to 10,000 patients in the US. The defining characteristic of Prader-Willi is hyperphagia, which is an intense persistent sensation of hunger.

現在我將簡要評論我們的後期臨床項目以及最近獲得許可的 ACP-711。我將從針對普拉德-威利症候群的 ACP-101 計劃開始。提醒一下，普拉德威利症候群是一種罕見的遺傳性神經行為障礙，在美國影響著大約 8,000 至 10,000 名患者。普拉德-威利症候群的典型特徵是暴食症，即持續強烈的飢餓感。

The symptoms of hyperphagia appear very early in life, often leading 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.

暴食症的症狀在生命早期就出現，常常導致肥胖和各種併發症，如第 2 型糖尿病或心臟病，以及焦慮和攻擊性等行為變化。不幸的是，目前的預期壽命僅為30歲左右，這主要是由於心血管疾病。

Carbetocin, a long-acting analog of human oxytocin, was developed to more selectively bind to the oxytocin receptor. With ACP-101, we're delivering carbetocin intranasally to provide direct delivery to the brain. Our current Phase 3 study called COMPASS PWS is global, multicenter, randomized, double-blind, and placebo-controlled.

卡貝縮宮素是人類催產素的長效類似物，其開發目的是更有選擇性地與催產素受體結合。利用 ACP-101，我們透過鼻腔內輸送卡貝縮宮素，直接輸送至大腦。我們目前進行的 3 期研究名為 COMPASS PWS，是一項全球性、多中心、隨機、雙盲和安慰劑對照的研究。

The trial design is informed by prior Phase 3 experience in terms of both dose and endpoint selection. As we shared last month, we expect this trial to be fully enrolled by the fourth quarter of this year, setting us up to see top-line results in the first half of 2026.

試驗設計參考了劑量和終點選擇的先前第 3 階段經驗。正如我們上個月所分享的，我們預計這項試驗將在今年第四季完成招募，這將使我們能夠在 2026 年上半年看到頂線結果。

Turning next to our second late-stage clinical program, ACP-204. ACP-204 is a new 5HT2A inverse agonist that's been designed based on learnings from pimavanserin. We have three specific areas of focus with ACP-204.

接下來談談我們的第二個後期臨床計畫 ACP-204。ACP-204 是一種新型 5HT2A 反向激動劑，其設計基於對匹莫範色林的研究。我們對 ACP-204 有三個特定的關注領域。

The first is to mitigate or eliminate the QT prolongation signal seen with pimavanserin; second, to enable testing of higher doses of ACP-204; and third, to improve time to onset of action. Our data to date are supportive of each of these. We're starting to share these data at medical meetings, with publications in the medical literature planned to follow.

第一是減輕或消除匹莫範色林所見的 QT 延長訊號；第二，能夠測試更高劑量的 ACP-204；第三，縮短起效時間。我們迄今為止的數據都支持上述觀點。我們開始在醫學會議上分享這些數據，並計劃隨後在醫學文獻中發表。

For example, in December, at the American College of Neuropsychopharmacology meeting, we shared some of the nonclinical characterization we've done with ACP-204. Of particular importance, ACP-204 demonstrated lower potency for certain cardiac ion channels, supporting a lower likelihood for QT prolongation.

例如，在 12 月的美國神經精神藥理學會會議上，我們分享了對 ACP-204 進行的一些非臨床表徵。特別重要的是，ACP-204 對某些心臟離子通道表現出較低的效力，從而降低了 QT 延長的可能性。

Beyond the nonclinical program, our Phase 1 program included over 200 patients, which we intend to publish through the course of this year. With this promising foundation, the first indication we are pursuing with ACP-204 is Alzheimer's disease psychosis, a condition about 30% of Alzheimer's patients develop that commonly consists of hallucinations and delusions.

除了非臨床項目之外，我們的第一階段項目還包括 200 多名患者，我們打算在今年內公佈結果。在這個充滿希望的基礎之上，我們利用 ACP-204 探索的第一個適應症是阿茲海默症精神病，大約 30% 的阿茲海默症患者會出現這種疾病，通常表現為幻覺和妄想。

Currently, we are testing ACP-204 in a global double-blind, placebo-controlled Phase 2 study. We've designed the program for seamless enrollment from Phase 2 to Phase 3. As with ACP-101, we provided our first substantive update on the timeline for this program last month. We plan to have the Phase 2 enrolled by the first quarter of 2026 and then see those top-line results around the middle of next year.

目前，我們正在全球雙盲、安慰劑對照的 2 期研究中測試 ACP-204。我們設計了該計劃以實現從第 2 階段到第 3 階段的無縫註冊。與 ACP-101 一樣，我們上個月首次對該計劃的時間表進行了實質更新。我們計劃在 2026 年第一季完成第二階段的招募，然後在明年年中左右看到最重要的結果。

We've also announced plans to study ACP-204 in a second indication, Lewy Body Dementia Psychosis or LBDP, which is a disease associated with abnormal deposits of a protein called alpha-synuclein in the brain. Patients living with Lewy Body Dementia can have changes to thinking, movement, behavior, and mood.

我們也宣布了研究 ACP-204 的第二種適應症，即路易氏體失智症或 LBDP，這是一種與大腦中一種名為 α-突觸核蛋白的蛋白質異常沉積有關的疾病。患有路易氏體失智症的患者的思維、動作、行為和情緒會改變。

Lewy Body Dementia is one of the most common causes of dementia. In the US alone, it is estimated that over one million people are affected. In prior studies with pimavanserin, there were promising results in the small subgroup of patients with LBDP, suggesting that ACP-204 could have the potential to provide a meaningful impact on hallucinations and delusions for this profoundly impacted patient population. We plan to initiate a Phase 2 study of LBDP in the third quarter of this year.

路易氏體失智症是癡呆症最常見的原因之一。據估計，光在美國就有超過一百萬人受到影響。在先前對匹莫範色林的研究中，一小部分 LBDP 患者取得了有希望的結果，這表明 ACP-204 有可能對這一深受影響的患者群體的幻覺和妄想產生有意義的影響。我們計劃在今年第三季啟動 LBDP 的第二階段研究。

I'll now turn to our newest addition to our clinical stage pipeline, ACP-711. In November of last year, we announced an exclusive license from Saniona for ACP-711, a potential first-in-class, highly selective GABA alpha 3 positive allosteric modulator that we have chosen to develop for the treatment of essential tremor.

現在我將介紹我們臨床階段產品線的最新成員 ACP-711。去年 11 月，我們宣布獲得 Saniona 的 ACP-711 獨家許可，ACP-711 是一種潛在的首創、高選擇性 GABA α3 正變構調節劑，我們選擇將其開髮用於治療特發性震顫。

Essential tremor is characterized by shaking and uncontrollable movements, mainly in the upper body. It may include difficulty using the hands, a shaky voice, and a nodding head, all of which can worsen over time. In addition to its functional impacts, essential tremor can lead to social avoidance and a reduced quality of life. Essential tremor is common, impacting roughly seven million patients in the US with roughly a million of them currently receiving some kind of therapy.

特發性震顫的特徵是顫抖和無法控制的運動，主要發生在上身。它可能包括雙手使用困難、聲音顫抖和點頭，所有這些症狀都會隨著時間的推移而惡化。除了對功能的影響外，特發性震顫還會導致社交迴避和生活品質下降。特發性震顫很常見，美國約有 700 萬名患者患有此病，其中約 100 萬人目前正在接受某種治療。

The only approved product for essential tremor came to the market in the US more than 50 years ago. And literature estimates suggest that as many as half of treated patients don't improve with treatment. We look forward to initiating a Phase 2 study in 2026. Between now and then, we're collecting more data in Phase 1. Our particular focus is an elderly cohort to ensure that our dosing and development plans take into account the needs of the full potential patient population.

唯一核准的治療特發性震顫的產品於 50 多年前在美國上市。文獻估計表明，多達一半接受治療的患者病情並沒有改善。我們期待在 2026 年啟動第二階段研究。從現在到那時，我們將在第一階段收集更多數據。我們特別關注老年人群體，以確保我們的劑量和開發計劃能夠考慮所有潛在患者群體的需求。

Before I conclude, a quick comment on our upcoming R&D Day on June 25. As Catherine mentioned at the beginning of the call, last month, we shared for the first time a more expanded view of our pipeline, showing the breadth of programs in development across a range of indications, mechanisms of action, and stages. We look forward to spending some time on the newly disclosed parts of our pipeline at our R&D Day as well as the opportunity to introduce some additional members of ACADIA's R&D team.

在結束之前，我想先簡單評論一下我們即將於 6 月 25 日舉行的研發日。正如凱瑟琳在電話會議開始時提到的那樣，上個月，我們首次分享了我們產品線的更廣泛的視圖，展示了正在開發的項目在一系列適應症、作用機制和階段的廣度。我們期待在研發日花一些時間討論我們新揭露的管道部分，並有機會介紹 ACADIA 研發團隊的其他成員。

And now I'll turn it over to Mark for a financial update.

現在我將把時間交給馬克來報告財務最新情況。

Thank you, Liz. Let's now review our fourth-quarter and full-year 2024 financial results. In the fourth quarter of 2024, we recorded $259.6 million in total revenue, up 12% from the fourth quarter of last year. For the full-year 2024, we recorded $957.8 million of total revenue, up 32% from the prior year.

謝謝你，莉茲。現在讓我們回顧一下 2024 年第四季和全年的財務表現。2024 年第四季度，我們的總營收為 2.596 億美元，比去年第四季成長 12%。2024 年全年，我們的總收入為 9.578 億美元，比上一年增長 32%。

Fourth-quarter DAYBUE net product sales were $96.7 million, up 11% year over year. Sequentially, DAYBUE sales were up 6% from the third quarter, comprised of 5% volume growth and 1% net price growth. Full-year DAYBUE sales were $348.4 million, up 97% compared to $177.2 million for the full-year 2023. DAYBUE gross-to-net was 18.8% for the year.

第四季 DAYBUE 淨產品銷售額為 9,670 萬美元，較去年同期成長 11%。與第三季相比，DAYBUE 的銷售額成長了 6%，其中銷量成長了 5%，淨價成長了 1%。DAYBUE 全年銷售額為 3.484 億美元，較 2023 年全年的 1.772 億美元成長 97%。DAYBUE 全年總淨利率為 18.8%。

Fourth-quarter NUPLAZID net product sales were $162.9 million, up 13% year over year, essentially split evenly between volume and net price. NUPLAZID gross-to-net for the quarter was 23.2%. Full-year NUPLAZID net product sales were $609.4 million, up 11% compared to $549.2 million in the prior year. The increase in net sales for the year was also essentially split evenly between volume and net price. The NUPLAZID gross-to-net adjustment for the full year was 26.1%.

NUPLAZID 第四季淨產品銷售額為 1.629 億美元，年增 13%，銷售量和淨價基本上持平。NUPLAZID 本季毛利與淨利比率為 23.2%。NUPLAZID 全年淨產品銷售額為 6.094 億美元，較上年的 5.492 億美元成長 11%。全年淨銷售額的成長也基本上由銷量和淨價平均分配。NUPLAZID 全年毛利與淨利調整率為 26.1%。

R&D expenses for the full year decreased to $303.2 million in 2024 from $351.6 million in 2023, mainly due to decreased business development payments in 2024, partially offset by increased costs from clinical stage programs. SG&A expenses for the full year increased to $488.4 million in 2024 from $406.6 million in 2023, primarily driven by increased marketing costs to support the NUPLAZID and DAYBUE brands in the US, investments to support commercialization of DAYBUE outside the US, and one-time costs related to our CEO transition.

全年研發費用從 2023 年的 3.516 億美元下降至 2024 年的 3.032 億美元，主要原因是 2024 年業務發展支出減少，但臨床階段專案成本增加部分抵銷了這一影響。全年銷售、一般及行政費用 (SG&A) 從 2023 年的 4.066 億美元增至 2024 年的 4.884 億美元，主要原因是支持美國 NUPLAZID 和 DAYBUE 品牌的營銷成本增加、支持美國以外 DAYBUE 商業化的投資以及與首席執行官過渡相關的一次性成本。

Our cash balance at the end of 2024 was $756 million, substantially up from our cash balance on December 31, 2023, of $438.9 million, primarily driven by cash flows from operations and the net proceeds resulting from the sale of our priority review voucher for $146.5 million in Q4 2024. Let's turn to our 2025 guidance.

我們 2024 年底的現金餘額為 7.56 億美元，大幅高於 2023 年 12 月 31 日的現金餘額 4.389 億美元，主要受經營活動現金流以及 2024 年第四季以 1.465 億美元出售優先審查券所產生的淨收益所驅動。讓我們轉向 2025 年的指引。

We expect total revenues in 2025 to be in the range of $1.03 billion to $1.095 billion. Beginning with DAYBUE, we expect US net sales for DAYBUE in 2025 to be in the range of $380 million to $405 million. While this guidance range takes into consideration many assumptions and scenarios, the primary factor influencing the range is the number of new patients who are referred into the top of the funnel for DAYBUE during 2025. At the midpoint of the range, we expect to generate approximately 10% more new patient referrals in 2025 as compared to 2024.

我們預計 2025 年總收入將在 10.3 億美元至 10.95 億美元之間。從 DAYBUE 開始，我們預計 2025 年 DAYBUE 在美國的淨銷售額將在 3.8 億美元至 4.05 億美元之間。雖然該指導範圍考慮了許多假設和情景，但影響範圍的主要因素是 2025 年期間轉診至 DAYBUE 漏斗頂端的新患者數量。在該範圍的中間值，我們預計 2025 年的新患者轉診量將比 2024 年增加約 10%。

In terms of total volume growth across the range, we anticipate 9% to 16% year-over-year growth as we only anticipate net price growth of approximately 0.5%. We project DAYBUE gross-to-net to be between 21.5% and 24.5%. Our gross-to-net is expected to increase year over year as we accrue additional rebates related to our early January pricing action, as well as accounting for the impact of the Medicare Part D redesign as part of the Inflation Reduction Act, where DAYBUE does not qualify for the specified small manufacturer phase-in as it was launched after August 16, 2022.

就整個系列的總量增長而言，我們預計將同比增長 9% 至 16%，因為我們預計淨價格僅增長約 0.5%。我們預計 DAYBUE 毛利率將在 21.5% 至 24.5% 之間。我們的毛利與淨利預計會逐年增加，因為我們會累積與 1 月初定價行動相關的額外回扣，同時考慮到作為《降低通貨膨脹法案》一部分的醫療保險 D 部分重新設計的影響，其中 DAYBUE 不符合指定的小型製造商分階段實施的資格，因為它是在 2022 年 8 月 16 日之後推出的。

I'd also like to share some additional insights on how we expect the year to progress for DAYBUE. We expect a sequential decline in DAYBUE net product sales in Q1. This is attributable to three factors: one, the fourth-quarter pull-through estimated to be approximately $3.5 million of net sales; two, typical beginning of the year seasonality in Q1; and three, a sequential decline in the net price per bottle of DAYBUE, which is primarily due to the accruals for the Medicare Part D redesign that I just mentioned.

我還想分享一些關於我們對 DAYBUE 今年發展的預期的額外見解。我們預計第一季 DAYBUE 淨產品銷售額將季減。這歸因於三個因素：一是第四季度淨銷售額預計約為 350 萬美元；二、第一季典型的年初季節性；第三，DAYBUE 每瓶淨價連續下降，這主要是由於我剛才提到的 Medicare Part D 重新設計的應計費用。

As we progress through the year, starting in Q2, we expect DAYBUE volumes and net price to increase on a quarter-by-quarter basis. In addition to US net sales for DAYBUE, we expect managed access program-related revenues in certain ex-US markets to contribute a modest amount of net sales in 2025. Net sales from ex-US markets are not included in our DAYBUE or total revenue guidance.

隨著今年的進展，從第二季開始，我們預計 DAYBUE 的銷售和淨價將逐季增加。除了 DAYBUE 在美國市場的淨銷售額外，我們預計某些美國以外市場的管理訪問計劃相關收入將在 2025 年貢獻適量的淨銷售額。我們的 DAYBUE 或總收入指引中不包括來自美國以外市場的淨銷售額。

Moving to NUPLAZID, we expect 2025 net sales to be in the range of $650 million to $690 million. At the midpoint of the range, we expect the net sales increase to be split roughly evenly between volume and net price.

轉向 NUPLAZID，我們預計 2025 年淨銷售額將在 6.5 億美元至 6.9 億美元之間。在該範圍的中間點，我們預期淨銷售額的成長將大致平均分配給銷售量和淨價。

We expect NUPLAZID gross-to-net to reduce by approximately 300 basis points due to the specified small manufacturer phase-in as part of the Inflation Reduction Act and for this reduction to be partially offset by gross-to-net increases in other channels. As such, we project gross-to-net for NUPLAZID to be between 22.5% and 25.5% for the full year. Furthermore, we no longer expect to see meaningful quarterly fluctuations in gross-to-net for NUPLAZID due to the Medicare Part D redesign.

我們預計，由於《通貨膨脹削減法案》中指定的小型製造商的逐步加入，NUPLAZID 的毛利對淨利將減少約 300 個基點，而這一減少將被其他渠道的毛利對淨利增加部分抵消。因此，我們預計 NUPLAZID 全年毛利率將在 22.5% 至 25.5% 之間。此外，由於 Medicare Part D 的重新設計，我們不再預期看到 NUPLAZID 的毛收入與淨收入有明顯的季度波動。

We expect R&D expense to be between $310 million and $330 million. The increase in R&D spend expected in 2025 compared to 2024 is primarily attributable to an increase in clinical and personnel costs as we advance and have broadened our R&D portfolio.

我們預計研發費用將在 3.1 億美元至 3.3 億美元之間。預計 2025 年研發支出將比 2024 年增加，這主要歸因於隨著我們不斷進步並擴大研發組合，臨床和人員成本也將增加。

We expect SG&A expense to be between $535 million and $565 million for the full year. The growth in SG&A year over year is primarily due to the continuation of DTC to support NUPLAZID, an increase in personnel costs to support DAYBUE in the US, and investments to support commercialization of DAYBUE outside the US.

我們預計全年銷售、一般及行政費用將在 5.35 億美元至 5.65 億美元之間。銷售、一般及行政費用同比增長主要由於 DTC 繼續支持 NUPLAZID、增加人員成本以支持美國境內的 DAYBUE，以及投資以支持美國境外 DAYBUE 的商業化。

Finally, with regard to the outlook for cash, while we expect to remain profitable on an operating basis, there are a number of cash outlays in 2025 that I'd like to call your attention to. These include payments to Neuren in Q1 2025 totaling approximately $98.8 million, reflecting both the payment of the initial sales milestone for DAYBUE, which was achieved in 2024, plus Neuren's share of the net proceeds from the sale of our priority review voucher. We also anticipate a net cash outflow of approximately $25 million related to the timing of rebate accruals netted against the payment of the first rebate invoice under the Inflation Reduction Act for NUPLAZID.

最後，關於現金前景，雖然我們預計在營運基礎上仍將保持盈利，但我想提請您注意 2025 年的一些現金支出。其中包括 2025 年第一季向 Neuren 支付的總額約為 9,880 萬美元的款項，既反映了 2024 年實現的 DAYBUE 初始銷售里程碑的付款，也反映了 Neuren 出售我們的優先審查憑證所獲得的淨收益份額。我們還預計，根據《通貨膨脹削減法案》向 NUPLAZID 支付第一張回扣發票時，將產生約 2,500 萬美元的淨現金流出。

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

現在我將把電話交給凱瑟琳，請她做最後發言。

Thanks, Mark. 2025 marks a new era for ACADIA, where we intend to drive substantial growth in our commercial brands to over $1 billion, globalize our business, and advance new innovations for the benefit of patients in need. As you can see on this slide, we expect to achieve a number of significant milestones in 2025 and 2026.

謝謝，馬克。 2025 年標誌著 ACADIA 的新時代，我們計劃推動我們的商業品牌大幅成長至 10 億美元以上，實現業務全球化，並推動新的創新，造福有需要的患者。正如您在這張投影片上看到的，我們預計在 2025 年和 2026 年實現許多重要的里程碑。

Now that we have filed our MAA for Europe, we will soon be making trofinetide available through managed access programs in certain ex-US countries, that will actually generate our first ex-US revenue in 2025 as we await approval in Europe anticipated in Q1 of 2026.

現在我們已經提交了針對歐洲的 MAA，我們很快就會透過某些美國以外國家的管理訪問計劃提供曲菲奈肽，這實際上將在 2025 年產生我們在美國以外的第一筆收入，同時我們等待預計在 2026 年第一季在歐洲獲得批准。

For ACP-101, we're expecting to have Phase 3 fully enrolled by the end of this year, with a top-line readout expected in the first half of 2026. In terms of ACP-204, we expect to complete enrollment early next year in our Phase 2 study in ADP, with top-line results expected around mid-2026. And we'll also initiate a Phase 2 study in LBDP in the third quarter of this year.

對於 ACP-101，我們預計第 3 階段將在今年年底前全面完成招募，並預計在 2026 年上半年獲得頂線讀數。就 ACP-204 而言，我們預計將於明年初完成 ADP 第 2 階段研究的招募，預計在 2026 年中期獲得頂線結果。我們也將在今年第三季啟動 LBDP 的第二階段研究。

From a corporate standpoint, it's a new era at ACADIA. We'll have our first-ever R&D Day. And as you can see from our guidance, we expect to exceed $1 billion in annual net sales, joining a very select group of companies in biotech. I'm really pleased with the progress we've made in recent months and excited to share more with you as the year unfolds.

從公司角度來看，ACADIA 已進入一個新時代。我們將舉辦有史以來的第一次研發日。正如您從我們的指導中看到的，我們預計年淨銷售額將超過 10 億美元，加入生物技術領域的少數公司之列。我對我們近幾個月來取得的進展感到非常高興，並很高興在新的一年與大家分享更多進展。

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

說完這些，我將把時間交給操作員進行問答。操作員？

(Operator Instructions) Ami Fadia, Needham & Company.

（操作員指示）Ami Fadia，Needham & Company。

Hi, good afternoon. Thanks for taking my question. Just with regards to DAYBUE, how should we think about sort of the evolution of gross-to-net over sort of the foreseeable future over the next one or two years? And where do you see this drug peaking as you continue to invest more behind growing the product?

嗨，下午好。感謝您回答我的問題。就 DAYBUE 而言，我們應該如何看待未來一兩年內可預見的總金額到淨額的演變？隨著您繼續加大對該產品的投入，您認為這種藥物的巔峰期會在哪裡？

And just with regards to NUPLAZID, there seems to be obviously an improvement in gross-to-net this year. How do we think about that over the next couple of years? Thank you.

就 NUPLAZID 而言，今年的毛利與淨利之比似乎明顯有所改善。在接下來的幾年我們會如何考慮這個問題？謝謝。

Thanks, Ami. Yeah, there's definitely some things with both gross-to-net that I think it's going to be helpful for Mark to give you a few more details around. So I'm going to ask Mark to talk to the DAYBUE and NUPLAZID gross-to-net as well as maybe talk about the peak sales.

謝謝，阿米。是的，我認為馬克向您提供一些有關毛收入與淨收入的詳細資訊將會很有幫助。因此，我將請馬克談談 DAYBUE 和 NUPLAZID 的總銷售額與淨銷售額，以及峰值銷售額。

Yeah. Thanks, Ami. On gross-to-net, starting with DAYBUE, we felt it was helpful to give some color this year, more specific color, as there are some changes year over year. As you see, it's kind of -- it's going to increase year over year, primarily due to us factoring in changes in the Medicare Part D redesign as it impacts DAYBUE.

是的。謝謝，阿米。關於總淨額，從 DAYBUE 開始，我們覺得今年給一些顏色、更具體的顏色是有幫助的，因為每年都會有一些變化。如您所見，它會逐年增加，主要是因為我們考慮了 Medicare Part D 重新設計的變化對 DAYBUE 的影響。

Medicare is less than 10% of the volumes of DAYBUE, but it does add a point or two to gross-to-net. As we see it evolving over kind of the next year, it's probably going to remain in this low 20 range, but of course, could fluctuate due to mix and fluctuate doing to future pricing actions as it may relate to rates of inflation going forward.

醫療保險佔 DAYBUE 業務量的 10% 以下，但它確實為總收入與淨收入之比增加了一到兩個百分點。正如我們所看到的，它在未來一年的發展趨勢是，它可能會保持在 20 的低位範圍內，但當然，它可能會因混合而波動，並因未來的定價行為而波動，因為它可能與未來的通貨膨脹率有關。

Transitioning to NUPLAZID, we had, again, a change this year due to the Medicare Part D redesign. We expect a 300-basis-point price benefit in gross-to-net due to that. There are other mix changes that influence our overall gross-to-net for NUPLAZID.

在過渡到 NUPLAZID 的過程中，由於 Medicare Part D 的重新設計，我們今年再次發生了變化。我們預計總淨利率將因此上漲 300 個基點。還有其他混合變化會影響 NUPLAZID 的整體毛利與淨利之比。

And as we do qualify for the small manufacturer benefit for NUPLAZID starting this year, that does unwind over the next handful of years. So you'll see NUPLAZID's gross-to-net inching up over time over the next several years.

由於我們從今年開始就有資格享受 NUPLAZID 的小型製造商福利，因此這項福利將在未來幾年內逐漸取消。因此，您會看到 NUPLAZID 的毛利與淨利潤之比在未來幾年內逐漸上升。

And as far as peak sales, thanks for the question on that. We -- it's been our policy not to give a specific point to DAYBUE peak sales. But our expectations from here is meaningfully growth above and beyond where we are this year. And we look to achieving that over the years to come.

至於峰值銷售，感謝您提出這個問題。我們的政策是不對 DAYBUE 的銷售高峰給出具體的數字。但我們的期望是，今年我們的業績將比現在有顯著成長。我們期待在未來幾年內實現這一目標。

Thanks, Mark.

謝謝，馬克。

Tess Romero, JPMorgan.

摩根大通的泰絲·羅梅羅。

Good afternoon, Catherine and team. Thanks so much for taking our question. So for DAYBUE, is the correct way to think about 1Q that you expect to have a decline in active patients on therapy from where you ended 4Q?

下午好，凱瑟琳和團隊。非常感謝您回答我們的問題。那麼對於 DAYBUE 來說，您認為第一季的正確思考方式是，從第四季末開始，接受治療的活躍患者數量會下降嗎？

And as a follow-up, is there a target number of patients that you think could be on or have been treated by the drug by the year-end here? And what is the long-term target you think you can get to in terms of penetration? Thanks so much.

另外，您認為今年底可以服用或已經服用該藥物治療的患者目標人數是多少？您認為在滲透率方面可以達到的長期目標是什麼？非常感謝。

Hey, Tess. Thank you. I appreciate the question. I'm going to let Mark talk about the Q1 dynamics that we're expecting. But the short answer on the decline in patients is no, but there are other dynamics going on. So I'm just going to ask Mark to give you a little color there. And then we can talk to the target number that's treated after he's taken you through that dynamic.

嘿，苔絲。謝謝。我很感謝你提出這個問題。我將讓馬克談談我們預期的第一季動態。但關於患者數量下降的簡短回答是否定的，但還有其他動態正在發生。所以我只是想請馬克跟你講一點故事。然後，在他向您介紹完該動態之後，我們可以談論要治療的目標人數。

Yeah. I think -- so Catherine kind of hit the point there on the -- the patient base is stable at this time. And so we'll continue to report the number of unique patients served, and we'll share the number for the first quarter on our next call. But it is stable. We don't expect a meaningful decline in patients sequentially.

是的。我認為——凱瑟琳說到點子上了——目前患者群體是穩定的。因此，我們將繼續報告所服務的獨特患者數量，並將在下次電話會議中分享第一季的數量。但它是穩定的。我們預計患者數量不會連續顯著下降。

What's driving our expectation for sequential revenue decline are a number of the things that I mentioned in my prepared remarks. One, we do have kind of the seasonal pull-forward of revenue between the first quarter back into last year's fourth quarter, as caregivers and families go through and anticipate their insurance renewal process early in the year. That does also impact overall utilization in the first quarter.

導致我們預期收入將連續下降的因素是我在準備好的發言中提到的一些因素。首先，由於護理人員和家庭在年初經歷並預期他們的保險續保過程，我們的收入確實從第一季度回落到去年第四季度，出現了季節性的提前。這也確實影響了第一季的整體利用率。

And we do expect, due to some of the changes in gross-to-net that I mentioned on the last question, to have a sequential decline in net price. So those are the factors that are really going to drive an expectation on a sequential revenue decline quarter over quarter, not due to a patient decline.

我們確實預計，由於我在上一個問題中提到的總淨價的一些變化，淨價將出現連續下降。因此，這些因素確實會導致收入逐季度下降，而不是因為患者人數下降。

Thanks, Mark. So I think in terms of the overall vision for the target numbers treated, I'm just going to ask Tom to sort of elaborate on some of the points you've already brought up in the call earlier and then talk about the future.

謝謝，馬克。因此，我認為就目標數字的整體願景而言，我只想請湯姆詳細說明您之前在電話中提出的一些觀點，然後談談未來。

Yeah. Thank you, Tess. Thank you for the call. So per the preprepared remarks, and as I mentioned, we still estimate that there's around 70% of the Rett population are yet to try DAYBUE. And as we think about our expansion strategy for the year ahead, tapping into that group of patients is going to be our number one priority.

是的。謝謝你，苔絲。謝謝您的來電。因此，根據預先準備好的評論，正如我所提到的，我們仍然估計大約 70% 的 Rett 人口尚未嘗試 DAYBUE。當我們考慮未來一年的擴張策略時，挖掘這群患者將是我們的首要任務。

Again, as you think about where those patients sit today and we think about our expansion strategy, especially with our broadened commercial footprint, we know that 65% of those patients currently are treated outside of a major center of excellence.

再說一次，當您思考這些患者目前所處的位置以及我們思考我們的擴張策略時，特別是隨著我們商業足蹟的擴大，我們知道目前 65% 的患者是在主要卓越中心之外接受治療的。

So our goal, given the relatively low penetration rates there of around 25%, is going to be a key focus for us as we expand our reach, expand our frequency so that those customers understand the value that DAYBUE offers when they have a discussion with a Rett patient or a Rett family.

因此，鑑於那裡的滲透率相對較低（約為 25%），我們的目標將成為我們擴大覆蓋範圍、增加服務頻率的重點，以便那些客戶在與雷特氏病患者或雷特氏病患者家人討論時能夠了解 DAYBUE 所提供的價值。

Thanks, Tom.

謝謝，湯姆。

Thanks, Tess.

謝謝，苔絲。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi, thanks for taking the questions. The first one is on -- I noticed since the last earnings call, there's been an increased estimate of diagnosed US patients from about 5,000 before to between 5,500 to 5,800 now. Could you kind of discuss how you arrived at that number and your confidence in that?

你好，謝謝你回答這個問題。第一個是——我注意到，自上次財報電話會議以來，美國確診患者的估計數量已從之前的約 5,000 人增加到現在的 5,500 至 5,800 人之間。您能否討論一下您是如何得出這個數字的以及您對此的信心？

And then as a second question is on ACP-711. Can you discuss how that compares with SAGE-324, which I think has a somewhat similar but different mechanism? And we saw that fail in Phase 2 in essential tremor last year. Thanks.

第二個問題是關於 ACP-711 的。您能否討論一下它與 SAGE-324 相比如何？我認為 SAGE-324 的機制有些相似，但又有所不同？去年，我們看到第二階段的特發性震顫治療失敗了。謝謝。

Yeah. Thanks, Joel. I'll take the diagnosed patients real quick, and then I'll transition over to Liz. So as you know, when we launched DAYBUE, we were talking about around 5,000 diagnosed patients in the US. And as we've been through the last sort of two years, we've gone up to 5,500 and now 5,800. And we continue to monitor that.

是的。謝謝，喬爾。我會很快接收確診的病人，然後交給 Liz。如你所知，當我們推出 DAYBUE 時，我們談論的是美國約有 5,000 名確診患者。在過去的兩年裡，我們的人數增加到 5,500 人，現在是 5,800 人。我們將繼續監測此事。

We have a number of different data sources that we look at in terms of ICD-10 codes, et cetera, that come in from the various sources. So we keep track of that. And it's -- I would sort of say it's normal for a rare disease to see an increase in diagnosed patients, especially for the first-in-market products. It tends to drive patients in. But also as payers ask for specific diagnoses, clinics tend to tighten up the diagnostics around each patient.

我們有許多不同的資料來源，我們會根據 ICD-10 程式碼等來查看這些資料來源，這些資料來源來自不同的來源。因此我們會跟踪這一點。而且——我想說，對於罕見疾病來說，確診患者數量的增加是正常的，尤其是對於首次上市的產品。它往往會吸引病人前來。但由於付款人要求具體的診斷，診所往往會加強對每位患者的診斷。

And so that's typically tracking to what we would expect, around a sort of a 10% to 15% increase. That will probably start to plateau. But for now, that's how we're getting the data. So Liz, why don't you take the 711 question?

因此，這通常與我們預期的一致，增幅約為 10% 至 15%。這一水平可能將開始趨於平穩。但就目前而言，這就是我們獲取數據的方式。那麼，Liz，為什麼不回答 711 個問題呢？

Yeah, absolutely. So thank you for the question. The SAGE program and 711 are similar insofar as they are both targeted at GABA. But I think there's a very important distinction here, which is that the SAGE program was really -- had impact across different GABA-containing receptors.

是的，絕對是如此。謝謝你的提問。SAGE 計劃和 711 類似，因為它們都針對 GABA。但我認為這裡有一個非常重要的區別，那就是 SAGE 計劃確實對不同的含 GABA 受體產生了影響。

And part of what we really like with 711 is that this really has the opportunity to focus in on alpha 3 containing receptors. And we think this gives us the best opportunity to really target the dysregulation and the dysfunction that you see in the GABA system in essential tremor, while sparing some of the potential safety side effects.

我們真正喜歡 711 的部分原因是，它確實有機會專注於含有 alpha 3 受體。我們認為這為我們提供了最好的機會來真正針對特發性震顫中 GABA 系統中出現的失調和功能障礙，同時避免一些潛在的安全副作用。

Thanks, Liz. Hopefully, that answers the question, Joel.

謝謝，莉茲。希望這能回答這個問題，喬爾。

Marc Goodman, Leerink Partners.

馬克古德曼（Marc Goodman），Leerink Partners。

Hi, good afternoon. Thank you for taking our questions. This is Basma, on for Marc. Our first question is related to 204 and its life cycle management strategy.

嗨，下午好。感謝您回答我們的問題。這是巴斯瑪 (Basma)，代替馬克 (Marc)。我們的第一個問題與 204 及其生命週期管理策略有關。

Given that you recently initiated a new trial in dementia with Lewy bodies, if the drug proved to be efficacious in both Alzheimer's disease psychosis and Lewy bodies, would you expect going back to the FDA and maybe revive the whole basket trial opportunity in other dementia-related psychosis?

鑑於您最近啟動了一項針對路易體癡呆症的新試驗，如果該藥物被證明對阿茲海默症精神病和路易體均有效，您是否會考慮回到 FDA 並可能恢復針對其他癡呆症相關精神病的整個一攬子試驗機會？

And we have another question on NUPLAZID regarding the product awareness. You mentioned before that it's gone down from 30% in 2020 to 8% currently. What is your goal with the current unbranded campaign in terms of the -- what level of awareness you need to achieve? And what is the timeline for that? Thank you.

我們還有另一個關於 NUPLAZID 產品知名度的問題。您之前提到過，它從 2020 年的 30% 下降到了目前的 8%。就您需要達到的知名度而言，您目前非品牌活動的目標是什麼？時間表是怎樣的？謝謝。

So let's have Liz take the 204 question first, and then both -- we'll tackle the NUPLAZID question.

因此，我們讓 Liz 先回答 204 個問題，然後我們再解決 NUPLAZID 問題。

Yeah. Thank you. So for ACP-204, we are investigating both in our currently ongoing trial in Alzheimer's disease psychosis as well as our planned upcoming trial in dementia with Lewy bodies and -- sorry, Lewy Body Dementia.

是的。謝謝。因此，對於 ACP-204，我們正在研究目前正在進行的阿茲海默症精神病試驗以及我們計劃即將進行的路易氏體失智症試驗——抱歉，是路易氏體失智症。

And we would not anticipate going to FDA to try to get a dementia-related psychosis type of approval in the future. I think what we've learned through our interactions over time is that it's very important to FDA to see impact in the specific disease under consideration. So we do plan to continue with those two separately.

我們預計未來不會向 FDA 申請與癡呆症相關的精神病類型的批准。我認為，透過長期的互動，我們了解到，對於 FDA 來說，了解所考慮的特定疾病的影響非常重要。因此我們確實計劃繼續分別處理這兩個問題。

Our currently existent Phase 2, Phase 3 program for Alzheimer's disease psychosis, we anticipate, is going to be consistent with the data package that we would need to support approval, assuming we see the results we're looking to see in that program. And we would design the Lewy body trial based on the results we see out of the Phase 2.

我們預計，我們目前針對阿茲海默症精神病的第 2 階段、第 3 階段計劃將與我們支持批准所需的資料包一致，假設我們看到了我們希望在該計劃中看到的結果。我們將根據第二階段的結果設計路易氏體試驗。

Thanks, Liz. In terms of NUPLAZID, I think you were referring us back to last call where we talked about the reason for launching the DTC campaign, which was the low levels of unaided awareness around hallucinations and delusions amongst caregivers.

謝謝，莉茲。關於 NUPLAZID，我想您指的是上次通話中我們討論的啟動 DTC 活動的原因，即護理人員對幻覺和妄想的獨立意識水平較低。

And the reason to start the campaign was to raise that awareness and therefore, encourage them to come into their doctors and ask for a conversation about treatments. And so we have been measuring awareness, and we now see that at a much higher level.

發起這項活動的目的是提高人們的意識，從而鼓勵他們向醫生諮詢治療事宜。因此，我們一直在衡量意識，現在我們看到了更高的水平。

But Tom, I wonder if you could also talk to some of the other DTC we're now seeing for patients coming in to sort of help the team understand a little bit more about the metric.

但是湯姆，我想知道您是否可以與我們現在為患者看到的其他一些 DTC 進行交談，以幫助團隊更多地了解該指標。

Absolutely. So as we mentioned during the opening remarks, our goal behind both the branded and unbranded campaigns is to ensure that patients are aware as to what ADP means and what they should be doing as they kind of run into the symptoms associated with the disease.

絕對地。正如我們在開幕詞中提到的那樣，我們進行品牌和非品牌活動的目標都是確保患者了解 ADP 的含義以及在遇到與疾病相關的症狀時應該做什麼。

We're actually seeing some really nice uptick in terms of engagement from our -- both our branded and unbranded campaigns, driving traffic to both the unaided awareness campaign, the More to Parkinson's, but also to nuplazid.com.

實際上，我們看到我們的品牌和非品牌活動的參與度都有了非常好的提升，不僅為無輔助宣傳活動、更多關於帕金森症的活動帶來了流量，也為 nuplazid.com 帶來了流量。

Remember, the primary goal behind doing this is making sure that we have patients who may be suffering from delusions and hallucinations, engaging with their caregiver, A, to discuss the disease itself, but also then to have a discussion around NUPLAZID. And we've been really encouraged by the early metrics that we're seeing, bearing in mind that this campaign only really went live in the middle of Q3.

請記住，這樣做的主要目的是確保我們可能患有妄想和幻覺的患者與他們的護理人員 A 一起討論疾病本身，同時也圍繞 NUPLAZID 進行討論。我們對所看到的早期指標感到非常鼓舞，請記住，這項活動實際上只是在第三季中期開始上線。

So more to come. But again, this is what gives us a good sense that we are leaving 2024 with some good momentum as we move into 2025.

未來還會有更多。但同樣，這讓我們有一個很好的感覺，在邁入 2025 年時，我們將以良好的勢頭告別 2024 年。

I think just to put a period behind that, Tom talked earlier about the increase in the market share that we've seen in NUPLAZID. And that was in our NBRxs. And we've seen that jump from 20% to 25% by the end of last year.

我想只是為了說明一下，湯姆之前談到了我們在 NUPLAZID 中看到的市場份額的成長。那就是在我們的 NBRxs 中。到去年年底，我們已經看到這一比例從 20% 躍升至 25%。

So again, just to show that the campaign is not only raising awareness and driving action, but actually, we're now seeing new scripts come through. So we're very encouraged by those specifics. Thanks for the question.

所以，再次表明，這場活動不僅提高了人們的認識並推動了行動，而且實際上，我們現在看到了新的劇本的出現。因此這些細節讓我們深受鼓舞。謝謝你的提問。

Thank you.

謝謝。

Tazeen Ahmad, Bank of America Securities.

Tazeen Ahmad，美國銀行證券。

Hi, guys. Can you hear me?

嗨，大家好。你聽得到我嗎？

We can.

我們可以。

Okay. Great. Thank you. I had a question on Prader-Willi. As you think about the secondary endpoints that are going to be important to look at, can you talk to us about some of those and what we should be looking for with those secondaries?

好的。偉大的。謝謝。我對普拉德威利症候群有一個疑問。當您考慮需要關注的重要次要終點時，您能否與我們談談其中的一些以及我們應該對這些次要終點進行哪些關注？

And maybe an overall question about the competitive landscape in Prader-Willi. It does seem like a few companies are pursuing approaches with different twists to treat the same disease. And I was curious about what you think if there is just one right approach, and if not, what the advantage of your approach could be? Thanks.

也許這是一個關於普拉德-威利症候群競爭格局的總體問題。看起來確實有幾家公司正在採用不同的方法來治療同一種疾病。我很好奇，如果只有正確的方法，您怎麼看？如果沒有，您的方法有什麼優勢？謝謝。

Thanks, Tazeen. So I'll let Liz answer specifically more about the trial. I think just at a high level, in areas of unmet medical need like Prader-Willi, we are very confident that there will be multiple mechanisms of action that are going to be able to treat patients, especially looking at the fact that we're targeting different areas than Soleno is. But Liz, why don't you maybe talk more specifically to some of the specifics of the trials?

謝謝，Tazeen。因此，我將讓 Liz 更具體地回答有關試驗的問題。我認為，從高層次來看，在普拉德-威利症候群等尚未滿足的醫療需求領域，我們非常有信心會有多種作用機制來治療患者，特別是考慮到我們針對的領域與 Soleno 不同。但是利茲，為什麼不更具體地談談試驗的一些細節呢？

Yeah. So as I think about our trial and how we think about that in the context of the overall landscape. So what I'll say is that we believe, and I think there is good appreciation in the community, that hyperphagia is in and of itself a really important portion of the patient and family experience here.

是的。因此，當我思考我們的試驗以及我們如何在整體背景下考慮它時。所以我想說的是，我們相信，而且我認為社區對此有很好的認識，那就是暴食症本身是病人和家屬體驗中非常重要的一部分。

And so I think that really, we've designed our study to focus on hyperphagia as the primary endpoint. And that is reflective of the fact that we think this is quite important in terms of the overall patient and family experience.

所以我認為，我們設計的研究其實是以暴食症作為主要終點。這反映出我們認為這對患者和家庭的整體體驗非常重要。

So I think that really seeing an impact there, seeing an impact on -- we have not just the continuous variable, which is our primary endpoint, but we also are looking at defined responder levels, which I think is going to be important to help people contextualize the extent of benefit they might expect with ACP-101 treatment.

因此，我認為真正看到影響，看到影響——我們不僅有連續變量（這是我們的主要終點），而且我們還在研究定義的響應者水平，我認為這對於幫助人們了解他們可能期望通過 ACP-101 治療獲得的益處程度非常重要。

I think those are going to be primarily important in terms of how we evaluate success in our 101 trial. Certainly, there are other assessments that we have in our secondary endpoints, looking at caregivers' assessment and physicians' assessment. And those are important as well. But I think that the hyperphagia being able to impact there is going to be very meaningful.

我認為這些對於我們如何評估 101 試驗的成功至關重要。當然，我們在次要終點還有其他評估，包括護理人員的評估和醫生的評估。這些也很重要。但我認為，暴食症能夠產生影響將會非常有意義。

I'll just echo what Catherine says in terms of -- there are a number of different approaches out there. And I think that -- and we think that this reflects the fact that this is a complex patient population with different needs. For example, one of the other programs that's out there is focusing in particular on the daytime sleepiness.

我只是重複凱瑟琳的說法——有很多不同的方法。我認為這反映了一個事實，即患者群體很複雜，有不同的需求。例如，另一個現有的項目特別關注白天嗜睡問題。

So there's a lot that goes on in this patient population. And again, to echo, we think there is room for multiple agents that work in different ways that meet the needs of individual patients.

因此，在這個患者群體中發生了很多事情。再次強調，我們認為有空間容納多種以不同方式發揮作用的藥物，以滿足個別患者的需求。

Thanks, Liz. Thanks, Tazeen.

謝謝，莉茲。謝謝，Tazeen。

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

Hi, there. This is Julian, on for Paul. Thanks so much for taking our question. On the NUPLAZID guide, it's a little bit wider than what you provided in years past. Can you just talk a little bit about the swing factors there and what could be driving potential incremental uncertainty?

你好呀。這是朱利安，代替保羅。非常感謝您回答我們的問題。在 NUPLAZID 指南中，它比過去幾年提供的內容要寬一些。您能否簡單談談其中的波動因素以及可能導致潛在增量不確定性的因素？

And then for the EU, obviously, a large opportunity with just the prevalence of Rett in the continent. I guess, what gives you confidence that the data you've generated, thus far, will allow you to achieve favorable reimbursement in that region? Thank you.

顯然，對歐盟來說，雷特病在歐盟大陸的流行是一個巨大的機會。我想，是什麼讓您有信心，到目前為止所產生的數據將使您能夠在該地區獲得有利的報銷？謝謝。

Thanks, Julian. So yeah, we've guided NUPLAZID with slightly wider guidance this year versus last year. I'll ask Mark to take you through some of the thinking.

謝謝，朱利安。是的，與去年相比，我們今年對 NUPLAZID 的指導範圍略寬。我會讓馬克向你們講解我的一些想法。

What I'll say at the outset is we've aimed for our guidance to be pragmatic and achievable. And I feel very comfortable with the ranges that we've set for both brands this year. But there are some specific dynamics going on with NUPLAZID, particularly around the new Medicare landscape. But I'll just let Mark talk to a little bit.

首先我想說的是，我們的目標是製定務實且可行的指導方針。我對我們今年為這兩個品牌設定的範圍感到非常滿意。但 NUPLAZID 有一些特定的動態，特別是在新的醫療保險格局方面。但我只會讓馬克講一點。

Yeah. I think Tom highlighted kind of our commercial initiatives. So there's a range of volume that can come out of the effectiveness of that, which I would put to your question kind of would be more our typical range for NUPLAZID.

是的。我認為湯姆強調了我們的商業舉措。因此，其有效性可以產生一定範圍的量，對於您的問題，我想說的是，這更像是 NUPLAZID 的典型範圍。

What's new this year is the Medicare Part D redesign as it possibly could impact volume. I talked about impact to net price earlier. So there's some potential tailwinds as well as headwinds. As you know, the patient out-of-pocket cost this year will be less. So that can provide incremental benefit on volume, while on the payer side, their costs will be increasing.

今年的新變化是醫療保險 D 部分的重新設計，因為它可能會影響數量。我之前談到了對淨價的影響。因此，存在一些潛在的順風和逆風。大家知道，今年病人的自付費用將會減少。這樣就可以在數量上提供增量效益，而在付款方，他們的成本就會增加。

So it's possible that there could be some headwinds there. So with this just being a new environment and some uncertainty, we thought it was prudent to widen the range, as our expectations could be a little broader this year than they have been in previous years.

因此，那裡可能會出現一些阻力。因此，鑑於這只是一個新環境和一些不確定性，我們認為擴大範圍是明智之舉，因為今年我們的預期可能比往年更廣泛一些。

And I think it's fair to say as we move through the year and we see the impact of those dynamics, we start to understand them better that we'll look to guide to a narrow range. But we wanted to start the year with a nod to the fact that the Medicare landscape is quite volatile, and we wanted to really understand it before we narrowed our guidance. So with that, I'll ask for next question.

我認為可以公平地說，隨著我們度過這一年，我們看到了這些動態的影響，我們開始更好地理解它們，我們將尋求引導到一個狹窄的範圍內。但我們想在年初就承認醫​​療保險格局相當不穩定，我們希望在縮小指導範圍之前真正了解這一點。那麼，我將提出下一個問題。

Our next question comes from --

我們的下一個問題來自--

Sorry, Shannon, I apologize. Julian had another question around the EU, which I've not forgotten but temporarily did. So Tom, why don't you talk to our EU confidence and what we're doing there?

對不起，香農，我很抱歉。朱利安還有另一個有關歐盟的問題，我沒有忘記，只是暫時忘記了。那麼湯姆，為什麼不談談我們對歐盟的信心以及我們在那裡所做的事情呢？

Sure. So as I mentioned during the prepared remarks, we're very excited about the opportunity that we believe exists in Europe. We can already say that we've had a number of requests from rep caregivers asking for the drug already, which we're handling carefully and judiciously.

當然。正如我在準備好的演講中提到的那樣，我們對歐洲存在的機會感到非常興奮。我們已經收到了許多代表護理人員對這種藥物的請求，我們正在謹慎而明智地處理這些請求。

And at the same time, as I also referenced, we're building a highly tenured, experienced but focused team that's going to be based in Zug to really make sure that we can meet the demands of the European market quickly, as we see an approval that we're anticipating in Q1 of next year.

同時，正如我所提到的，我們正在組建一支資深、經驗豐富且專注的團隊，該團隊將駐紮在楚格，以確保我們能夠迅速滿足歐洲市場的需求，因為我們預計明年第一季將獲得批准。

So I think the engagement that we're seeing from thought leaders, KOLs, and also the patient community has been really, really encouraging, which gives us a good sense as to where we're going. I think as it comes to kind of the data, obviously, we are generating more data all of the time.

因此，我認為，思想領袖、關鍵意見領袖以及患者群體的參與確實非常令人鼓舞，這讓我們清楚地了解我們的發展方向。我認為就資料類型而言，顯然我們一直在產生更多的資料。

We'll have our additional data from LOTUS this year that's continuing. And we believe that this will give us a supplementary opportunity to really bolster our filing as we go through the European discussion. So we feel very confident about DAYBUE's outlook in Europe.

今年我們將持續從 LOTUS 取得更多數據。我們相信，這將為我們提供一個補充機會，讓我們在參與歐洲討論時真正加強我們的申請。因此我們對DAYBUE在歐洲的前景非常有信心。

Thanks, Tom. So now we can open up the next question. Thanks, Shannon.

謝謝，湯姆。現在我們可以開始下一個問題了。謝謝，香農。

Gregory Renza, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。

Great. Thank you. Catherine and team, congrats on the progress, and thanks for taking my question. Catherine, you've aptly noted that ACADIA's pipeline looks vastly different than even a quarter ago. And as you build that out, I'm just curious with respect to exploring those additional external investments that you speak of, where are the current gaps in ACADIA's portfolio right now?

偉大的。謝謝。凱瑟琳和團隊，祝賀你們的進展，感謝你們回答我的問題。凱瑟琳，您準確地指出，ACADIA 的管道與一個季度前相比有很大不同。當您建立這個概念時，我只是很好奇，對於探索您提到的那些額外的外部投資，ACADIA 目前的投資組合中存在哪些差距？

Perhaps a little color on where you see dimensions of rightsizing and getting to the optimal pipeline state, whether it's across the stage, the technical success, or even the area of therapeutic interest. Thank you very much.

也許在您看到適當規模和達到最佳管道狀態的維度上有一些色彩，無論是跨階段、技術成功，還是治療興趣領域。非常感謝。

Thanks, Greg. Thank you for acknowledging the pipeline. We are excited for the milestones that we're going to be looking at in both '25 and '26 and also the additional color that Liz and the team will be sharing at our R&D Day. And we're all very excited about the possibilities within there to deliver on our promise.

謝謝，格雷格。感謝您對管道的認可。我們對即將在 25 年和 26 年看到的里程碑以及 Liz 和團隊將在我們的研發日分享的更多色彩感到興奮。我們都對實現承諾的可能性感到非常興奮。

But as you say, ACADIA has always had a strong eye to BD. That's how we've built our company, and we continue to focus there. I think with our strong balance sheet, which Mark outlined earlier, we're excited to look at our neuroscience core areas, our neuro-rare core areas, but also as we announced earlier this year to look at some additional areas in rare in aligned therapeutic spaces, such as endocrine, cardiovascular, immunology, which might also fit under the ACADIA capabilities and competencies, and allow us to sort of expand our expertise beyond neuro-rare into those adjacent spaces.

但正如你所說，ACADIA 一直密切關注 BD。這就是我們建立公司的方式，我們將繼續專注於此。我認為，憑藉馬克之前概述的強勁資產負債表，我們很高興看到我們的神經科學核心領域、我們的神經罕見核心領域，而且正如我們今年早些時候宣布的那樣，我們將研究一些其他罕見的治療領域，例如內分泌、心血管、免疫學，這些領域也可能符合 ACADIA 的能力和能力，並使我們能夠將我們的專業知識從神經罕見擴展到那些相鄰的領域。

I think as the team come out of several investor meetings earlier this year, and we move into sort of the end of Q1, we're very diligent about looking at opportunities. We're looking to fill our pipeline at any stage. I think the key for us is our high bar for strong clinical and scientific evidence, looking at areas of high unmet medical need where a company like ACADIA can play to win and importantly, where we can bring to market something that's either first-in-class or potentially best-in-class.

我認為，隨著團隊在今年稍早參加了幾次投資者會議，並且進入第一季末，我們非常勤奮地尋找機會。我們希望在任何階段都能填補我們的管道。我認為對我們來說關鍵在於我們對強有力的臨床和科學證據的高標準，專注於那些尚未滿足的醫療需求領域，像 ACADIA 這樣的公司可以在這些領域中取勝，更重要的是，我們可以在這些領域將一流的或可能是一流的產品推向市場。

And I think that's been written with NUPLAZID and DAYBUE. It will be the same for 101 and 204 and 711. And that's the bar that we will hold that Liz keeps held high to and that we will continue to focus on. So thanks for the question.

我認為這是用 NUPLAZID 和 DAYBUE 寫的。101、204 和 711 也是如此。這就是我們所堅持的標準，莉茲會一直堅守這個標準，我們也會繼續關注這個標準。感謝您的提問。

Charles Duncan, Cantor.

查爾斯鄧肯，領唱者。

Yeah, thank you for taking the question. Congrats, Catherine and team, on the commercial execution '24 and refreshed communication. I appreciate all the guidance. But I had a pipeline question, and specifically around ACP-101, I noted that you are enrolling a big range in terms of age 5 to 30, and that's not new.

是的，感謝您回答這個問題。恭喜凱瑟琳和團隊在 24 年的商業執行和更新溝通方面的成就。我感謝所有的指導。但我有一個關於渠道的問題，特別是關於 ACP-101，我注意到你們招收的年齡範圍從 5 歲到 30 歲不等，這並不是什麼新鮮事。

But I'm wondering if Liz has a thought on the dynamic range of HQ-CT and whether or not she expects there to be an age-related, call it, impact on being able to see a signal. And if there is an open-label extension study going, has there been rollover, and is there persistence in that? Thanks.

但我想知道 Liz 是否考慮過 HQ-CT 的動態範圍，以及她是否認為年齡會對訊號接收能力產生影響。如果正在進行開放標籤擴展研究，是否有延續性，並且是否有持續性？謝謝。

Hi, Charles, great to hear from you. I'm going to ask Liz to take that.

你好，查爾斯，很高興收到你的來信。我要讓 Liz 拿走它。

Yeah. So Charles, great to hear from you. Thanks for the great question. As usual, I'll start with the easy one first, which is, yes, we do have an open-label extension for the program. And we are seeing good rollover into that, which I try not to overread, but that's always at least a neutral to positive sign that patients are interested in continuing on to the open-label extension.

是的。查爾斯，很高興收到你的來信。謝謝你提出這個好問題。像往常一樣，我先從簡單的開始，是的，我們確實有一個針對該計劃的開放標籤擴展。我們看到了良好的進展，我盡量不去過度解讀，但這始終至少是一個中性到積極的信號，表明患者有興趣繼續進行開放標籤擴展。

As far as the dynamic range of age, I don't know that we have tremendously strong data out there across the age range. That said, this is a lifelong disease for these patients. We think it's important to generate information that helps us understand the impact across the age range. And we think that we're well set up to do that in this study. So I think that we don't have the perfect answer, but I do think that it is important to make sure that we understand the impact across the patient population.

就年齡的動態範圍而言，我不知道我們是否擁有涵蓋整個年齡範圍的極其強大的數據。也就是說，對這些患者來說，這是一種終身疾病。我們認為，產生有助於我們了解各個年齡層的影響的資訊非常重要。我們認為，我們已經做好了充分的準備，可以在這項研究中做到這一點。所以我認為我們沒有完美的答案，但我確實認為確保我們了解整個患者群體的影響非常重要。

Right. I think it's something that we're definitely going to learn through the study, right? Good question. Thank you, Charles. Next question, operator?

正確的。我認為這是我們透過研究肯定會學到的東西，對嗎？好問題。謝謝你，查爾斯。接線員，下一個問題是什麼？

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Hey, guys. This is [Athena], on for Ritu. Thanks for taking the question. Some questions on DAYBUE. You mentioned that more stable patients have been titrated to the recommended doses. What percentage does that represent out of all the patients who are currently on drug?

嘿，大家好。我是 [Athena]，代表 Ritu 發言。感謝您回答這個問題。關於 DAYBUE 的一些問題。您提到，病情更加穩定的患者已依照建議劑量進行治療。在所有正在服藥的患者中，這佔多少百分比？

You also noted there was a 15% improvement in discontinuation rates. What drove this improvement? And what strategies is your expanded sales force going to try and deploy to maintain the stable utilization of DAYBUE? Thank you.

您還注意到停藥率提高了 15%。是什麼推動了這項改善？您擴大的銷售團隊將嘗試部署哪些策略來維持 DAYBUE 的穩定使用率？謝謝。

Thanks, [Athena]. I'm going to ask Tom to give you some color on those questions.

謝謝，[雅典娜]。我要請湯姆來幫你解釋一下這些問題。

Okay. So thank you for the question. So focusing on consumption to begin with, so yeah, we continue to see consumption actually tick upwards slightly over time. At the moment, on average, for the complete cohort of patients we've had on treatment since launch, we're seeing about a 70% alignment with our target label.

好的。謝謝你的提問。因此，首先關註消費，是的，我們繼續看到消費實際上隨著時間的推移而略有上升。目前，平均而言，自推出新藥以來接受治療的所有患者中，有 70% 的患者與我們的目標標籤一致。

So that is kind of reflective of the fact that we know that patients do titrate their dose on occasions per guidance that they're potentially getting from their HCP. But 70% is kind of what we're seeing, and that's what we saw tick up slightly through the end of the year towards 75%. So we're encouraged by what that looks like.

所以這在某種程度上反映了這樣一個事實：我們知道患者確實會根據他們從 HCP 那裡得到的指導偶爾調整劑量。但我們看到的比例是 70%，到年底這一比例略有上升，接近 75%。因此，我們對這一結果感到鼓舞。

In terms of your second question, which was regarding the 15% discontinuations, so as you know, we've learned a great deal both about the Rett patient journey, but also about DAYBUE dynamics since we have launched the product. And one thing that we have learned is, obviously, the requirements of starting a patient really well, making sure that they understand what to expect with DAYBUE as they begin treatment. And through our ACADIA Connect team -- and we have a dedicated team of family access managers -- we can make sure that they get one-to-one care as they start their DAYBUE journey.

關於您的第二個問題，即有關 15% 的停藥率，如您所知，自從我們推出該產品以來，我們已經了解了很多有關 Rett 患者旅程以及 DAYBUE 動態的知識。我們學到的一件事顯然是，開始治療患者時必須確保他們了解 DAYBUE 治療的效果。透過我們的 ACADIA Connect 團隊（我們擁有一支專門的家庭訪問經理團隊），我們可以確保他們在開始 DAYBUE 旅程時得到一對一的護理。

So a lot of this is just around education. It's making sure that they understand what to expect with DAYBUE, how to make sure that we make sure that they have everything on hand that's needed to be able to manage that patient as they start the product, and that they fully appreciate the value that they're going to see with DAYBUE for the long term. Because one thing that we're going to be focused on a great deal through 2025 is ensuring that the benefit and the efficacy message, both for our HCPs and consumers, is writ large.

所以很多都跟教育有關。這是為了確保他們了解 DAYBUE 的功效，如何確保他們在開始使用產品時擁有管理患者所需的一切，並確保他們充分認識到 DAYBUE 的長期價值。因為到 2025 年，我們要重點關注的一件事就是確保我們的 HCP 和消費者都能充分了解其益處和功效。

The other thing that I would want to mention -- and I think we mentioned this during both my prepared remarks and Mark's -- is that we do now have this very stable group of patients. 60% of our patients have now been on treatment for greater than 12 months or longer.

我想提及的另一件事——我想我們在我和馬克的準備好的發言中都提到了這一點——就是我們現在確實有一群非常穩定的患者。我們 60% 的患者目前接受治療的時間已超過 12 個月或更長。

So we're encouraged that we have this growing and stable base of patients. And that, again, given that dynamic, we actually do see our consumption rates ticking up over time. So I hope that answers the question.

因此，我們很高興看到我們擁有不斷成長且穩定的患者群體。而且，考慮到這種動態，我們確實看到我們的消費率隨著時間的推移而上升。我希望這能回答這個問題。

Thanks, Athena. We'll take the next question.

謝謝，雅典娜。我們將回答下一個問題。

Sumant Kulkarni, Canaccord Genuity.

Sumant Kulkarni，Canaccord Genuity。

Good afternoon. Thanks for taking my question. It's a bit of a bigger picture question, but has a specific ACADIA-related angle.

午安.感謝您回答我的問題。這是一個更大的問題，但有一個與 ACADIA 相關的具體角度。

Given you're well into your Phase 3 program in Prader-Willi, do you foresee any changes at the FDA that might make things different versus what you might currently expect in terms of a potential back and forth with the agency on the data that you generate in what is a high unmet need indication?

鑑於您已順利進入 Prader-Willi 症候群的 3 期臨床試驗，您是否預見到 FDA 會發生一些變化，這些變化可能會使事情與您目前預期的不同，即在與 FDA 就您在高未滿足需求指標中生成的數據進行潛在溝通方面？

Thanks for the question. We thought somebody might ask about FDA interactions. So yes, Liz, would you want to talk to that?

謝謝你的提問。我們以為有人可能會詢問有關 FDA 交互作用的問題。是的，莉茲，你想談談這個嗎？

Yeah. I mean, it's a little hard to speculate right now. I think that this is obviously quickly evolving space. We know that there was a memo that came out just today about potential -- across all agencies, potential reorganizations and large-scale risks.

是的。我的意思是，現在有點難以推測。我認為這顯然是一個快速發展的空間。我們知道今天剛發布了一份關於所有機構的潛在重組和大規模風險的備忘錄。

So what I'll say so far is that we have not yet seen impact on our interactions and I would say generally, broadly speaking, not specific to PWS. But broadly speaking, we've not seen either changes in time or in tenor of those interactions. But we, like everyone else in the space, are going to be watching this carefully and carefully keeping an eye on the tenor of regulatory interactions we have over time.

所以到目前為止我想說的是，我們還沒有看到它對我們互動的影響，而且我想說，一般來說，廣義上講，它並不特定於 PWS。但從廣義上講，我們並沒有看到這些互動在時間或基調上發生變化。但我們和該領域的其他所有人一樣，將密切關注這一情況，並密切關注我們長期以來的監管互動進展。

Yeah. Talk about (inaudible) thank you, Liz, and thanks for the question, Sumant.

是的。談（聽不清楚）謝謝你，Liz，也謝謝你的提問，Sumant。

Thank you.

謝謝。

So I think now we're --

所以我認為現在我們--

I would now like to turn the call back over to Catherine Owen Adams for closing remarks.

現在我想將電話轉回給凱瑟琳·歐文·亞當斯，請她作最後發言。

I'd just like to thank everybody for their questions today and for their interest in ACADIA, and look forward to connecting with you, all, in the future. Thanks.

我只想感謝大家今天提出的問題以及對 ACADIA 的關注，並期待將來與大家建立聯繫。謝謝。

This concludes today's conference call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。