ACADIA Pharmaceuticals Inc (ACAD) 2025 Q1 法說會逐字稿

Good day ladies, and gentlemen and welcome to the ACADIA Pharmaceuticals conference call. My name is Lauren Cannon, and I'll be your coordinator for today. (Operator Instructions) Please be advised that today's conference is being recorded.

女士們、先生們，大家好，歡迎參加 ACADIA Pharmaceuticals 電話會議。我叫勞倫‧坎農 (Lauren Cannon)，今天我將擔任您的協調員。（操作員指示）請注意，今天的會議正在錄音。

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。

Good afternoon, and thank you for joining us on today's call to discuss ACADIA's first-quarter 2025 financial 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 Tom Garner, our Chief Commercial Officer, who will discuss our strong commercial brand's DAYBUE in NUPLAZID.

下午好，感謝您參加今天的電話會議，討論 ACADIA 2025 年第一季的財務表現。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，她將致一些開場白；接下來是我們的首席商務官湯姆·加納 (Tom Garner)，他將在 NUPLAZID 討論我們強大的商業品牌 DAYBUE。

Also joining us today is Elizabeth 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, 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 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，這些陳述僅在今天做出，並且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.

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. We're off to a strong start in 2025. Our performance this quarter reflects solid execution across the business and continued momentum behind our strategic priorities. From commercial progress to pipeline advancement, we're delivering on our commitments whilst positioning ACADIA for long-term growth.

謝謝你，艾爾。大家下午好，感謝大家的參與。2025 年，我們將迎來一個強勁的開局。本季度的業績反映了整個業務的穩健執行以及我們策略重點的持續發展勢頭。從商業進展到管道推進，我們正在履行承諾，同時也為 ACADIA 的長期成長做好準備。

Let me walk you through the key highlights, starting with our commercial performance. We're pleased to report that our commercial business has had a strong first quarter, building on the solid foundation we established in 2024, with first-quarter revenues of $244.3 million, up 19% from a year ago. Starting with DAYBUE, this quarter represents a meaningful inflection point in the brand's trajectory.

讓我向您介紹主要亮點，首先從我們的商業表現開始。我們很高興地報告，我們的商業業務在第一季表現強勁，這得益於我們在 2024 年建立的堅實基礎，第一季營收為 2.443 億美元，比去年同期成長 19%。從 DAYBUE 開始，本季代表了品牌發展軌蹟的一個有意義的轉折點。

Over the past few quarters, we've successfully stabilized the business and established a solid base of growth to build on. Today, our focus is shifting towards accelerating that growth through deeper patient and provider engagement and by broadening our overall reach into the community. We generated $84.6 million in DAYBUE sales in the first quarter, up 11% from a year ago.

在過去的幾個季度中，我們成功穩定了業務並建立了堅實的成長基礎。今天，我們的重點正轉向透過更深入的患者和提供者參與以及擴大我們在社區的整體影響力來加速這一增長。第一季度，DAYBUE 的銷售額達到 8,460 萬美元，比去年同期成長 11%。

Importantly, the number of unique patients receiving shipments was 954, up meaningfully from Q4, and in fact, an all-time record for the brand. This gives us confidence in the sustainability of DAYBUE's growth and we reiterate our four-year sales guidance. Turning to NUPLAZID, we reported $159.7 million in revenue for the quarter, up 23% from the prior year. As Mark will detail, that growth included 6% growth in volume, and the remainder was largely attributable to one-time changes in growth to net.

重要的是，接收貨物的獨立患者數量為 954 人，較第四季度大幅增加，事實上，創下了該品牌的歷史最高紀錄。這使我們對 DAYBUE 成長的可持續性充滿信心，我們重申我們的四年銷售指導。談到 NUPLAZID，我們報告本季營收為 1.597 億美元，比上年成長 23%。正如馬克所詳述的，這一增長包括 6% 的銷售增長，其餘部分主要歸因於淨增長的一次性變化。

We continue to see strong performance driven by our direct consumer efforts which are helping drive patient awareness and pull-through in the form of physician visits. As with DAYBUE, we are reiterating our four-year guidance for NUPLAZID and expect continued solid execution throughout the year. On the R&D front, we're making great progress and are thrilled to update you that our timeline for last patient in and therefore top-line results from our COMPASS PWS Phase 3 study in Prader-Willi Syndrome are now both expected to happen before the end of 2025.

我們繼續看到強勁的業績，這得益於我們直接面向消費者的努力，這些努力有助於提高患者意識並以醫生就診的形式促成患者就診。與 DAYBUE 一樣，我們重申對 NUPLAZID 的四年指導，並預計全年將繼續穩步執行。在研發方面，我們正在取得巨大進展，並很高興地向您通報，我們針對普拉德威利綜合徵的 COMPASS PWS 第三階段研究的最後一名患者的時間表以及頂級結果預計都將在 2025 年底之前完成。

We're also excited to host our first ever R&D Day next month. This event will offer a deeper look into our development strategy and allow us to showcase some of the promising innovation that's taking shape across our pipeline. We look forward to introducing you to more members of our team and sharing how we're thinking about the next wave of growth.

我們也很高興下個月舉辦我們的首屆研發日。這項活動將使我們更深入地了解我們的發展策略，並讓我們展示正在形成的一些有前景的創新。我們期待向您介紹我們團隊的更多成員，並分享我們對下一波成長的看法。

With that, I'd like to turn the call over to Tom to discuss our commercial performance in the first quarter.

說到這裡，我想把電話轉給湯姆，討論我們第一季的商業表現。

Thank you, Catherine. I'll begin with a review of DAYBUE, where we have made exciting progress. First-quarter sales were $84.6 million, up 11% from a year ago. Although sales were down sequentially, as we explained would be the case on our last call, the underlying patient dynamics were positive. During the quarter, 954 unique patients received paid shipments, up from 920 in the fourth quarter. In fact, as Catherine said, this was the highest number of patients served in a quarter since the launch of DAYBUE over two years ago.

謝謝你，凱瑟琳。我首先回顧 DAYBUE，我們在其中取得了令人興奮的進展。第一季銷售額為 8,460 萬美元，比去年同期成長 11%。儘管銷售額環比下降，正如我們在上次電話會議上解釋的那樣，但潛在的患者動態是積極的。本季度，共有 954 名獨立患者收到了付費發貨，高於第四季度的 920 名。事實上，正如凱瑟琳所說，這是 DAYBUE 兩年多前推出以來，一個季度內服務的患者人數最多的一次。

While we continue to add new patients, a key driver of this performance was a significant reduction in discontinuations and improvements in persistency. Discontinuations were down 35% sequentially from the fourth quarter of 2024 and declined 66% compared to the first quarter of 2024. Overall, our persistency rate remains above 50% after 12 months, driving a growing, stable base of patients to remain on therapy long-term, with 65% of our active patients now having been on therapy for 12 months or longer.

雖然我們繼續增加新患者，但這一業績表現的關鍵驅動因素是停藥人數的大幅減少和堅持治療的提高。停產數量與 2024 年第四季相比較上季下降 35%，與 2024 年第一季相比下降 66%。總體而言，我們的持續率在 12 個月後仍保持在 50% 以上，推動越來越穩定的患者長期接受治療，目前 65% 的活躍患者已經接受治療 12 個月或更長時間。

With regard to the patient mix, our strategy is playing out as intended. In the first quarter, we saw more new scripts from the community setting, including a higher number of prescriptions from pediatricians. This was particularly encouraging as it occurred ahead of the field force expansion, which we announced in the first quarter.

就患者組合而言，我們的策略正在按預期進行。在第一季度，我們看到來自社區的新處方增多，其中兒科醫生開出的處方數量也增多。這尤其令人鼓舞，因為它發生在我們第一季宣布的現場人員擴張之前。

I'm pleased to share that all planned hires for the expansion have now been completed, and I'm confident our expanded customer model and refined strategy will begin contributing to further DAYBUE sales growth in the second half of the year. As a reminder, to date, roughly two-thirds of diagnosed Rett syndrome patients have yet to try DAYBUE.

我很高興地告訴大家，擴張計畫的所有招募現已完成，我相信我們擴展的客戶模式和完善的策略將在今年下半年開始促進 DAYBUE 銷售的進一步成長。提醒一下，到目前為止，大約三分之二的確診為雷特氏症的患者尚未嘗試過 DAYBUE。

Turning to our plans outside of the US, we continue to lay the foundation for a strong launch outside the US once we obtain approval from the EMA, which we anticipate in the first quarter of 2026. As a reminder, the opportunity in Europe is substantial, with an estimated 9,000 to 12,000 individuals affected by Rett syndrome.

談到我們在美國以外的計劃，一旦我們獲得 EMA 的批准，我們將繼續為在美國以外強勢推出奠定基礎，我們預計將在 2026 年第一季獲得批准。需要提醒的是，歐洲的機會是巨大的，估計有 9,000 至 12,000 人患有雷特氏症。

We have now hired an experienced general manager for Europe and continue to build out the commercial team behind him. We have also initiated managed access programs and, in April, have already served the first Rett syndrome patient under this program in Germany. We continue to see strong interest in access to trofinetide prior to approval.

我們現在已經聘請了一位經驗豐富的歐洲總經理，並繼續在他身後組建商業團隊。我們還啟動了管理訪問計劃，並於今年 4 月在德國為該計劃下的第一位雷特氏症患者提供了服務。我們繼續看到人們對在批准之前使用曲菲奈肽的濃厚興趣。

For the rest of the world, we recently entered into distribution agreements for named patient access in geographies including Latin America, the Middle East, Asia Pacific, and other countries around the world and are already receiving inquiries. In summary, I'm very pleased with the progress we have made with DAYBUE.

對於世界其他地區，我們最近在拉丁美洲、中東、亞太地區和世界其他國家等地區簽訂了指定患者訪問的分銷協議，並且已經收到了詢問。總而言之，我對我們在 DAYBUE 方面取得的進展感到非常滿意。

As you can see from the first-quarter results, we have now started to see renewed growth in patients. And this gives us confidence that we will be able to accelerate growth in the second half of the year with our broadened field footprint as we expand penetration into the community setting. We believe we now have the strategy, structure and resources available to maximize growth through 2025 and into 2026.

從第一季的業績可以看出，我們現在開始看到患者數量再次成長。這使我們有信心，隨著我們擴大對社區環境的滲透，我們將能夠透過擴大領域覆蓋範圍來加速下半年的成長。我們相信，我們現在擁有可用的策略、結構和資源，可以實現 2025 年和 2026 年的最大成長。

Turning to NUPLAZID, we were pleased to see the strong momentum built throughout 2024 continue into 2025. NUPLAZID achieved first-quarter sales of $159.7 million, representing 23% revenue growth year over year, of which 6% came from volume. In fact, the first quarter of 2025 was the best quarter in terms of new-to-brand prescriptions since 2020. We believe this gives us strong momentum for the rest of the year, even as we have a significant opportunity to further expand our share of the Parkinson's disease psychosis market.

談到 NUPLAZID，我們很高興看到 2024 年全年的強勁勢頭延續到 2025 年。NUPLAZID 第一季銷售額達 1.597 億美元，較去年同期成長 23%，其中 6% 來自銷售量。事實上，2025 年第一季是自 2020 年以來新品牌處方量最好的季度。我們相信，這將為我們在今年剩餘時間內提供強勁動力，同時我們還有很大機會進一步擴大我們在帕金森氏症精神病市場的份額。

We continue to see the benefits from both our unbranded disease awareness campaign as well as our branded campaign. These efforts led to higher engagement across our unbranded disease awareness and NUPLAZID websites, helping to spark more meaningful conversations between patients and their physicians with a nearly 30% increase in awareness of Parkinson's-related hallucinations and delusions since the launch of the More to Parkinson's campaign.

我們持續看到非品牌疾病宣傳活動和品牌宣傳活動帶來的好處。這些努力提高了我們非品牌疾病意識和 NUPLAZID 網站的參與度，有助於激發患者和醫生之間更有意義的對話，自「了解更多帕金森氏症」活動啟動以來，對帕金森氏症相關幻覺和妄想的認識提高了近 30%。

Our consumer activation campaigns have complemented and enhanced the core growth drivers that have supported the NUPLAZID brand for over two years, including leveraging of our published real-world evidence showing an association of [pimavanserin renews] compared with other atypical antipsychotics in important outcomes like all-cause mortality.

我們的消費者活化活動補充並增強了支持 NUPLAZID 品牌兩年多來的核心成長動力，包括利用我們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，[pimavanserin renews] 在諸如全因死亡率等重要結果方面具有關聯。

From a brand perspective, our primary focus is on identifying PDP patients earlier in their Parkinson's journey and ensuring they're aware of available treatments upon diagnosis. It's crucial to remember that while approximately 50% of Parkinson's disease patients will experience hallucinations and delusions, it's estimated that only 10% will ever self-report these symptoms.

從品牌角度來看，我們的主要重點是儘早識別帕金森氏症患者，並確保他們在確診後了解可用的治療方法。必須記住的是，雖然大約 50% 的帕金森氏症患者會出現幻覺和妄想，但據估計只有 10% 的患者會自我報告這些症狀。

Therefore, we will continue to actively engage with the Parkinson's disease community across both HCP and consumer audiences to drive earlier awareness, diagnosis, and treatment of Parkinson's disease psychosis, and to help ensure that NUPLAZID is recognized as a first-line therapy for this challenging condition. Overall, we remain highly confident in our ability to drive meaningful growth for the brand through 2025 and beyond.

因此，我們將繼續積極與帕金森氏症社群（包括 HCP 和消費者群體）合作，推動對帕金森氏症精神病的早期認識、診斷和治療，並幫助確保 NUPLAZID 被認可為這種棘手疾病的一線療法。總體而言，我們對自己在 2025 年及以後推動品牌實現有意義的成長的能力仍然充滿信心。

I'll now turn it over to Liz.

現在我將把發言權交給 Liz。

Thanks, Tom. I'm delighted to start out today with an important update for our pipeline. As Catherine mentioned in her opening remarks, due to the diligence of our team and support of the community, the timeline for our COMPASS PWS Phase 3 trial for ACP-101 has accelerated. As a result, we now expect closed screening within the coming days. which would allow us to complete enrollment this quarter. With that, we're now expecting top-line results by early fourth quarter of this year.

謝謝，湯姆。我很高興今天能先介紹我們的管道的重要更新。正如凱瑟琳在開幕詞中提到的，由於我們團隊的勤奮和社區的支持，我們對 ACP-101 的 COMPASS PWS 第三階段試驗的時間表已經加快。因此，我們預計未來幾天內將進行閉門放映。這將使我們能夠在本季完成招生。因此，我們預計今年第四季初將公佈營收業績。

Assuming positive data, we believe that sets us up for a potential regulatory submission in the US in the first quarter of 2026. As a quick reminder, ACP-101 is an intranasal delivery of carbetocin, a long-lasting analog of human oxytocin. Carbetocin was developed to more selectively bind to the oxytocin receptor.

假設數據為正數，我們相信這將為我們在 2026 年第一季向美國提交監管文件做好準備。簡單提醒一下，ACP-101 是一種經鼻給藥的卡貝縮宮素，一種長效的人類催產素類似物。卡貝縮宮素的開發是為了更有選擇性地與催產素受體結合。

We're developing it for the treatment of hyperphagia in Prader-Willi, which is a rare genetic neurobehavioral disorder. Hyperphagia, an intense, persistent sensation of hunger, is a defining characteristic of Prader-Willi. Again, we're pleased to pull these important milestones into 2025 and look forward to reporting results later this year.

我們正在開發它用於治療普拉德-威利症候群的暴食症，這是一種罕見的遺傳性神經行為障礙。暴食症是一種強烈且持續的飢餓感，是普拉德-威利症候群的典型特徵。再次，我們很高興將這些重要的里程碑帶入 2025 年，並​​期待在今年稍後報告結果。

Next, I'll turn to our second late-stage clinical program, ACP-204, our new 5-HT2A inverse agonist that we designed based on learning from pimavanserin. We continue to make important progress with ACP-204 as well, now moving it forward in two indications. First, we're currently conducting a global, double-blind, placebo-controlled Phase 2 study in Alzheimer's disease psychosis, or ADP. We've designed the program for seamless enrollment from Phase 2 to Phase 3.

接下來，我將介紹我們的第二個後期臨床項目 ACP-204，這是我們基於對匹莫範色林的經驗而設計的新型 5-HT2A 反向激動劑。我們在 ACP-204 方面也持續取得重要進展，目前正朝著兩個適應症推進。首先，我們目前正在對阿茲海默症精神病（ADP）進行一項全球性的、雙盲的、安慰劑對照的 2 期研究。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。

For this program, we continue to expect last patient in during the first quarter of 2026, followed by topline results around mid-2026. We're also advancing ACP-204 into a second indication, Lewy body dementia psychosis, a serious neurodegenerative condition linked to alpha-synuclein buildup. and marked by cognitive, behavioral, and motor symptoms.Affecting over 1 million people in the US, LBD is one of the most common forms of dementia.

對於該項目，我們繼續預計最後一位患者將在 2026 年第一季入院，隨後在 2026 年中期獲得頂線結果。我們也正在將 ACP-204 推進到第二個適應症，即路易氏體失智症，這是一種與 α-突觸核蛋白積聚有關的嚴重神經退化性疾病。並以認知、行為和運動症狀為特徵。 LBD 是最常見的癡呆症之一，在美國影響超過 100 萬人。

Prior data with pimavanserin showed encouraging signals in this population, supporting the potential of ACP-204 to address hallucinations and delusions. For Lewy body dementia psychosis, we remain on track to initiate a Phase 2 study in the third quarter of this year. Now I'd like to turn to our updated pipeline and provide a few additional updates.

先前關於匹莫範色林的數據顯示出該族群的令人鼓舞的訊號，支持了 ACP-204 治療幻覺和妄想的潛力。對於路易氏體失智症精神病，我們仍有望在今年第三季啟動第二階段研究。現在我想談談我們更新的管道並提供一些額外的更新。

First, I'm looking forward to sharing more details on these programs at our R&D Day next month. In particular, I'm excited to share additional insight into our plans and the supportive data regarding some of our most newly disclosed programs. The event is intended to provide a bit of a deep dive into each of these programs as well as to allow you an opportunity to meet some of the senior members of our R&D team.

首先，我期待在下個月的研發日上分享有關這些計畫的更多細節。特別是，我很高興能與大家分享有關我們計劃的更多見解以及一些我們最新披露的計劃的支持數據。這項活動旨在讓您深入了解每個項目，並讓您有機會與我們研發團隊的一些高級成員見面。

We're also looking to give you an understanding of how we think about drug development here at ACADIA and the high bars we put on our potential medicines at every step along the way. You'll hear that from us as well as through input from KOLs, caregivers, and patient advocates who are our true north as we make tough decisions about what innovation to continue to pursue and where to focus our resources.

我們也希望讓您了解我們在 ACADIA 對藥物開發的看法，以及我們在整個過程中對潛在藥物設定的高標準。您將從我們這裡以及透過關鍵意見領袖、護理人員和患者倡導者的意見中聽到這些，他們是我們的真正方向，因為我們要做出艱難的決定，決定繼續追求哪些創新以及將資源集中在哪裡。

At this time, I want to share an update related to our collaboration with Stoke Therapeutics. We continue to be excited by the data we are seeing from the SYNGAP1 program and look forward to getting to the next decision-enabling data early next year. With respect to the other discovery programs in the collaboration, ACADIA has reached the conclusion that there is not a viable path forward for the Rett or the undisclosed program. Accordingly, we will be winding down our efforts for both of these programs.

此時，我想分享有關我們與 Stoke Therapeutics 合作的最新進展。我們繼續對從 SYNGAP1 計劃中看到的數據感到興奮，並期待在明年年初獲得下一個決策數據。對於合作中的其他發現項目，ACADIA 得出的結論是，Rett 或未公開的項目沒有可行的前進道路。因此，我們將逐步減少對這兩個項目的投入。

Finally, I wanted to provide a brief update on trofinetide. Our marketing authorization application for trofinetide in the EU remains under review, and we continue to anticipate approval in the first quarter of 2026. In Japan, our engagement with the PMDA remains productive. I'm pleased to share that we have officially received Orphan Drug designation. This has various benefits, but importantly, offers the potential for priority review. And we remain on track to initiate a Phase 3 trial in Japanese patients with Rett syndrome in the third quarter of this year.

最後，我想簡單介紹一下曲芬奈肽的最新情況。我們在歐盟的 Trofinetide 行銷授權申請仍在審查中，我們預計將於 2026 年第一季獲得批准。在日本，我們與PMDA的合作仍然富有成效。我很高興地告訴大家，我們已正式獲得孤兒藥稱號。這有各種好處，但重要的是，提供了優先審查的潛力。我們仍計劃於今年第三季針對日本雷特症候群患者啟動第三階段試驗。

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

現在，我將把財務更新交給馬克。

Thank you, Liz. Let's now review our first-quarter 2025 financial results. In the first quarter of 2025, we recorded $244.3 million in total revenue, up 19% from the first quarter of last year. First-quarter DAYBUE net product sales were $84.6 million, up 11% year over year, on the strength of achieving an all-time high in terms of number of unique patients receiving shipments.

謝謝你，莉茲。現在讓我們回顧一下 2025 年第一季的財務表現。2025年第一季度，我們的總營收為2.443億美元，比去年第一季成長19%。第一季 DAYBUE 淨產品銷售額為 8,460 萬美元，年成長 11%，這得益於接收貨物的獨立患者數量創下歷史新高。

As we signaled on our Q4 call in February, we expected the DAYBUE net sales to be down substantially. Factors contributing to this included the fourth-quarter pull forward of approximately $3.5 million in net sales, typical beginning of year seasonality impacting both volume and net price, and a sequential decline in net price per bottle of DAYBUE attributable to the impact of the Medicare Part D redesign.

正如我們在二月第四季電話會議上所暗示的那樣，我們預計 DAYBUE 淨銷售額將大幅下降。造成這一現象的因素包括第四季度淨銷售額提前約 350 萬美元、典型的年初季節性因素影響銷售和淨價，以及由於醫療保險 D 部分重新設計的影響，DAYBUE 每瓶淨價連續下降。

The DAYBUE gross net adjustment for the quarter was 24.9%. Importantly, we continue to expect all the key metrics that drive DAYBUE net sales to increase throughout the remainder of the year, including unique patient-served, bottle volumes, and net price.

本季 DAYBUE 總淨調整率為 24.9%。重要的是，我們繼續預計推動 DAYBUE 淨銷售額的所有關鍵指標將在今年剩餘時間內成長，包括服務的獨特患者、瓶裝量和淨價。

Turning next to NUPLAZID, first-quarter NUPLAZID net product sales were $159.7 million, up 23% year over year, with 6% attributable to volume. The anticipated net price benefit of 16% was largely attributable to a one-time change in gross to net as a result of the Medicare Part D redesign as part of the Inflation Reduction Act. Moving forward, we expect our gross to net to stabilize without significant quarterly fluctuations. And to remind you, ACADIA is benefiting from qualifying as a small company manufacturer under the Inflation Reduction Act.

接下來是 NUPLAZID，第一季 NUPLAZID 淨產品銷售額為 1.597 億美元，年增 23%，其中 6% 歸因於銷售量。預期的 16% 淨價格收益主要歸因於《通貨膨脹削減法案》中醫療保險 D 部分的重新設計導致的總額到淨額的一次性變化。展望未來，我們預期總收入與淨收入將保持穩定，不會有明顯的季度波動。需要提醒您的是，根據《通貨膨脹削減法案》，ACADIA 因獲得小型公司製造商資格而受益。

As a point of reference, our gross price for NUPLAZID in the quarter was up just over 2% year over year. The NUPLAZID gross-to-net adjustment for the quarter was 24.1%. R&D expenses were $78.3 million in the first quarter, up from $59.7 million from the first quarter of 2024 due to increased spend on clinical-stage programs.

作為參考，本季 NUPLAZID 的總價格比去年同期上漲了 2% 多一點。NUPLAZID 本季的毛利與淨利調整率為 24.1%。由於臨床階段項目支出增加，第一季研發費用為 7,830 萬美元，高於 2024 年第一季的 5,970 萬美元。

SG&A expenses for the quarter were $126.4 million, up from $108 million in the first quarter of 2024. The increase was primarily driven by the continuation of our NUPLAZID consumer activation campaigns, as well as higher commercial operation expenses for our planned expansion of the DAYBUE team.

本季銷售、一般及行政費用為 1.264 億美元，高於 2024 年第一季的 1.08 億美元。成長的主要原因是我們繼續進行 NUPLAZID 消費者活化活動，以及計劃擴大 DAYBUE 團隊而增加的商業營運費用。

Our cash balance as of March 31 was $681.6 billion. While cash flow from operating activities was positive in the quarter, cash declined sequentially primarily as a result of $98.8 million in payments made to Neuren, reflecting payments of a sales milestone and their share of the net proceeds from the sale of our PRV, as I explained on our last call.

截至 3 月 31 日，我們的現金餘額為 6,816 億美元。雖然本季經營活動產生的現金流為正，但現金環比下降，主要原因是向 Neuren 支付了 9,880 萬美元，這反映了銷售里程碑的付款及其在出售 PRV 淨收益中所佔的份額，正如我在上次電話會議上所解釋的那樣。

Let's turn to our 2025 guidance. As you can see on this slide, we are reiterating the full-year 2025 financial guidance first provided on February 26 with the exception of R&D expense. We now expect to spend $330 million to $350 million, up from our prior range of $310 million to $330 million. The increase is primarily related to the acceleration of the timeline for ACP-101, which is pulling forward spend from 2026.

讓我們轉向 2025 年的指引。正如您在這張投影片上看到的，我們重申了 2 月 26 日首次提供的 2025 年全年財務指導，但研發費用除外。我們現在預計支出 3.3 億至 3.5 億美元，高於先前的 3.1 億至 3.3 億美元。這一增長主要與 ACP-101 時間表的加速有關，該計劃將支出從 2026 年開始提前。

And to conclude, regarding uncertainty around the potential tariffs, it's important to note that for both NUPLAZID and DAYBUE, we have substantial inventory on hand in the United States. For NUPLAZID, we have enough inventory to meet anticipated demand into the mid to late 2030s; and for DAYBUE, we have a few years' worth of inventory.

最後，關於潛在關稅的不確定性，值得注意的是，對於 NUPLAZID 和 DAYBUE，我們在美國都有大量庫存。對於 NUPLAZID，我們有足夠的庫存來滿足到 2030 年代中後期的預期需求；對於 DAYBUE，我們有幾年的庫存。

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. Our first-quarter results reflect a strong start to 2025, and we are well-positioned to build on this momentum. We are eager to deliver on the value-creating milestones you see on this slide in 2025 and 2026. I'm pleased that one of those significant milestones has been accelerated, with top-line results from COMPASS PWS now expected in the fourth quarter of this year.

謝謝，馬克。我們第一季的業績反映了 2025 年的強勁開局，我們已做好準備，繼續保持這一勢頭。我們渴望在 2025 年和 2026 年實現您在這張投影片上看到的價值創造里程碑。我很高興看到其中一個重要里程碑的實現已經加快，COMPASS PWS 的頂線業績預計將在今年第四季公佈。

We have delivered on key commitments from our Q4 call, including expanding the DAYBUE field force and launching a global managed access program. We remain sharply focused on executing against our strategic priorities, accelerating DAYBUE's commercial trajectory, capitalizing on the continued momentum of NUPLAZID, expanding our global presence, and advancing a pipeline designed to deliver innovative therapies to underserved patient populations.

我們兌現了第四季度電話會議上做出的關鍵承諾，包括擴大 DAYBUE 現場力量和啟動全球管理訪問計劃。我們將繼續高度重視執行我們的策略重點，加速 DAYBUE 的商業發展軌跡，利用 NUPLAZID 的持續發展勢頭，擴大我們的全球影響力，並推進旨在為服務不足的患者群體提供創新療法的管道。

In line with this strategy, we're pleased to invite you to our inaugural R&D Day on June 25, which will be broadcast live. I look forward to keeping you updated as we execute through the remainder of the year.

根據這項策略，我們很高興邀請您參加我們於 6 月 25 日舉行的首屆研發日活動，屆時將進行現場直播。我期待在今年剩餘時間內向您通報最新進展。

And with that, I'll turn the call over to the operator. Operator?

說完這些，我就把電話轉給接線生。操作員？

(Operator Instructions) Ritu Baral, TD Cowen.

（操作員指示）Ritu Baral，TD Cowen。

Good afternoon, guys. Thanks for taking the question. I wanted to ask about, I guess, one question on 101, and then one question about DAYBUE for Europe. One, what does good 101 data look like? And can you discuss how that may relate to your last discussions with FDA on the filing strategy?

大家下午好。感謝您回答這個問題。我想問一個關於 101 的問題，然後問一個關於歐洲 DAYBUE 的問題。一、好的101數據是什麼樣的？您能否討論一下這與您上次與 FDA 就備案策略進行的討論有何關聯？

And then as far as Europe, how should we be thinking about modeling a European price for DAYBUE, and then just balancing the pricing risk from a potential most favored nation drug pricing development that I think we're all sort of watching? Thanks for taking the questions.

那麼就歐洲而言，我們應該如何考慮為 DAYBUE 建立歐洲價格模型，然後平衡潛在的最惠國藥品定價發展帶來的定價風險，我認為我們都在關注這一點？感謝您回答這些問題。

Thanks, Ritu. Appreciate those two-part questions. So I'm going to ask Liz to kick us off on 101, and then I'll talk about the EU strategy.

謝謝，Ritu。感謝這兩個部分的問題。因此，我將請 Liz 先討論 101 問題，然後我將討論歐盟戰略。

Thanks, Catherine. Hi, Ritu, and thanks for the question. First off, I do want to reiterate how very pleased we are to find ourselves ahead of schedule with respect to 101 and looking to have data out of this study by the end of the year, which we think is going to be a pretty important milestone for ACADIA as a company and really reflects both great effort by the team as well as, I think, good enthusiasm from the community. So positive all the way around.

謝謝，凱瑟琳。你好，Ritu，謝謝你的提問。首先，我想重申一下，我們非常高興能夠提前完成 101 計劃，並預計在今年年底前獲得研究數據，我們認為這對 ACADIA 公司來說是一個非常重要的里程碑，並且真正反映了團隊的巨大努力以及社區的熱情。一切都非常積極。

In terms of your question about what a good outcome would look like here, the nature of the trial is such that I'm going to be very pleased if what we have is a statistically significant result. We've powered this such that we think that if we have a statistical significance, we're going to have demonstrated a clinically meaningful impact on hyperphagia, which really is a defining and truly terrible symptom for these patients to be living with. There are a number of other things that we're looking at in this trial that we think are interesting, but that outcome on hyperphagia is really what's going to drive us here.

至於你問的什麼是好的結果，試驗的性質是這樣的，如果我們得到一個具有統計意義的結果，我會非常高興。我們對此進行了研究，認為如果具有統計意義，我們將證明其對暴食症具有臨床意義的影響，而暴食症確實是這些患者必須忍受的一個決定性且非常可怕的症狀。我們在這次試驗中研究了許多其他我們認為有趣的事情，但關於暴食症的結果才是我們真正關注的重點。

And then I'll start on the EU. It was a two-part question, Ritu, about the price in terms of modeling and then the most favored nation. Let me maybe start with most favored nations first. I think as we all look out into the unknown of the future of whatever might happen with the decisions on that, we are looking really to focus on the approval of DAYBUE in Europe.

然後我將開始談論歐盟。瑞圖，這個問題分為兩部分，一部分是關於建模方面的價格，另一部分是關於最惠國。我先從最惠國開始。我認為，當我們都在展望未來未知的局面時，無論這項決定會發生什麼，我們真正關注的是歐洲對 DAYBUE 的批准。

And then after that, as you know, reimbursement takes quite a period of time across the different member states and the countries, and we'll assess any specific recommendations that come out of the administration with respect to our most favored nation as we are able to sort of understand it and make decisions as we move forward on pricing and reimbursement in individual countries.

然後，正如你所知，報銷在不同的成員國和國家之間需要相當長的時間，我們將評估政府針對我們最惠國提出的任何具體建議，因為我們能夠理解它，並在我們推進各國的定價和報銷時做出決定。

With respect to EU price, I think we've spoken before about a number of rare analogs that are out there that you can probably use for your modeling. What I will say is that we are confident in getting a strong EU price that allows us to display the value that we believe we're bringing with DAYBUE to our patients in the Rett community. And we will continue to update you as we have those discussions moving forward. Thanks, Ritu.

關於歐盟價格，我想我們之前已經討論過一些可能用於建模的罕見類似物。我想說的是，我們有信心獲得一個強勁的歐盟價格，這使我們能夠展示我們相信 DAYBUE 為 Rett 社區患者帶來的價值。隨著討論的進展，我們將繼續向大家通報最新進展。謝謝，Ritu。

Thank you.

謝謝。

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 each of your brands, NUPLAZID and DAYBUE, what is the right way for us to be thinking about what we are likely to see sequentially from 1Q to 2Q from a growth perspective? What are the key factors and drivers we should be thinking about from a quarter-to-quarter basis as we are trying to model this out? Thank you.

下午好，凱瑟琳和團隊。非常感謝您回答我們的問題。那麼，對於你們的每一個品牌，NUPLAZID 和 DAYBUE，從成長角度來看，我們應該如何正確思考從第一季到第二季我們可能連續看到的情況？當我們嘗試對此進行建模時，我們應該逐季度考慮哪些關鍵因素和驅動因素？謝謝。

Thanks, Tess. I'm going to ask Tom to talk about maybe patient demands and then Mark to talk about more of the sort of the sequential financials, if that's okay. So Tom, why don't you kick us off?

謝謝，苔絲。如果可以的話，我將請湯姆談談患者的需求，然後請馬克談談更多關於連續財務狀況的問題。那麼湯姆，你為什麼不把我們踢出去呢？

Yes, thank you for the question. So I'll maybe start with DAYBUE. So as we shared, we had a good first quarter in terms of active patients. And we believe that that's going to continue. Q2, obviously, we'll begin to see the full impact of our expanded customer model, which, as a reminder, the primary goal behind that is making sure that we can really meet patients where they're seeing their treaters.

是的，謝謝你的提問。所以我可能會從 DAYBUE 開始。正如我們所分享的，就活躍患者而言，我們第一季表現良好。我們相信這種情況將會持續下去。Q2，顯然，我們將開始看到擴展的客戶模式的全部影響，提醒一下，其背後的主要目標是確保我們能夠真正在患者就診的地方與他們見面。

As a reminder, we are pretty under-penetrated outside of the COEs, and outside of the COEs represents around 65% of the overall Rett patient volume, so significant headroom for growth. I think with the expansion of our field model, which again, we've increased our field footprint across all functions by about 30%, we do anticipate that we will continue to see new patient adds at the top of the funnel, which is our primary focus.

提醒一下，我們在 COE 之外的滲透率相當低，而 COE 以外的患者約佔 Rett 患者總數的 65%，因此還有很大的成長空間。我認為，隨著我們現場模型的擴展，我們再次將所有職能領域的現場覆蓋範圍增加了約 30%，我們確實預計我們將繼續在漏斗頂部看到新的患者增加，這是我們的主要關注點。

And at the same time, as we shared, we continue to see really encouraging data regarding ongoing persistency and discontinuations continuing to decline. And I think that that reflects just the continued learning we've had around the product, making sure that we really support the Rett families as they start DAYBUE.

同時，正如我們所分享的，我們繼續看到關於持續堅持和中止持續下降的真正令人鼓舞的數據。我認為這反映了我們在產品方面不斷學習，確保我們在 Rett 家庭啟動 DAYBUE 時能夠真正為他們提供支援。

And encouragingly, as you look at the discontinuation data, we're seeing it across all of the cohorts that we've had since launch, including those who have been on treatment for less than three months, which is critically important as you think about modeling out the rest of the year, because we want to ensure that every single new patient start is able to continue for the long term. So that kind of touches upon DAYBUE.

令人鼓舞的是，當您查看停藥數據時，我們會發現自推出以來的所有患者群體都有停藥情況，包括接受治療不到三個月的患者，這對於您考慮模擬今年剩餘時間的情況至關重要，因為我們希望確保每一位新患者都能長期堅持治療。這有點觸及 DAYBUE。

I think for NUPLAZID we continue to be pleased with the impact that our unbranded and branded campaigns are having. We're seeing good momentum around referrals. Our NBRxs are looking positive. And as we mentioned, Q1 of '25 was actually the best quarter that we've had in nearly five years for NUPLAZID, and we believe that that encouraging momentum is something we will continue to pull on as we head through the rest of the year. Mark?

我認為對於 NUPLAZID 而言，我們對我們的非品牌和品牌活動所產生的影響感到滿意。我們看到推薦方面的勢頭良好。我們的 NBRxs 看起來很積極。正如我們所提到的，2025 年第一季實際上是 NUPLAZID 近五年來表現最好的季度，我們相信，我們將在今年剩餘時間內繼續保持這種令人鼓舞的勢頭。標記？

Yes, thanks, Tom. I think from a financial perspective, starting with DAYBUE, both brands, it's really going to be a volume story throughout the rest of the year, and Tom explained the operational dynamics. On DAYBUE, from kind of a net sales standpoint, we do expect kind of price to gradually increase over time as we benefit from Medicaid. As you remember, it DAYBUE largely in Medicaid patient populations, so the Medicaid pricing resets on a quarterly basis. So we should benefit from some price benefit over time about the inflation level.

是的，謝謝，湯姆。我認為從財務角度來看，從 DAYBUE 開始，這兩個品牌在今年剩餘時間內的銷售都會是一個大問題，湯姆解釋了營運動態。對於 DAYBUE，從淨銷售額的角度來看，隨著我們從醫療補助計劃中受益，我們確實預計價格會隨著時間的推移而逐漸上漲。您記得，DAYBUE 主要針對醫療補助患者群體，因此醫療補助定價每季重置一次。因此，隨著時間的推移，我們應該會從通貨膨脹水平的一些價格收益中受益。

And then in Q1, for a DAYBUE, we do tend to have higher Medicaid rebates because we have a segment of our patient population are dual-eligible Medicaid commercial payment patients. And those patients, as they get through their out-of-pocket maximums, tend to shift toward commercial payments over time. And so that also is a tailwind from a little bit of price.

然後在第一季度，對於 DAYBUE，我們確實傾向於獲得更高的醫療補助回扣，因為我們的一部分患者是雙重合格的醫療補助商業支付患者。當這些患者達到自付費用的最高限額時，他們往往會逐漸轉向商業支付。因此，這也是物價上漲帶來的順風。

As we've talked about on our last call and Tom mentioned, we've initiated our expansion of our DAYBUE field team and that we expect operationally to have a greater impact in the second half of the year. On NUPLAZID, I think it's probably more consistent. Our volume will drive the quarter-to-quarter performance. You don't have the same level of dynamics on changes in price over time.

正如我們在上次電話會議上討論過以及湯姆提到的那樣，我們已經開始擴大我們的 DAYBUE 現場團隊，並且我們預計在下半年的營運中將產生更大的影響。在 NUPLAZID 上，我認為它可能更加一致。我們的銷售將推動季度業績。您對價格隨時間的變化沒有相同程度的動態了解。

NUPLAZID's largely a Medicare patient population, so the pricing doesn't reset on a quarterly basis, so it's really a one-time reset towards the end of the year. So our gross to net subject to -- anything that can happen on a quarterly basis due to patient mix, should be mostly stable throughout the remainder of the year. We did have the big-time one-time adjustment, as we mentioned, comparing Q1 last year to this year. But going forward, probably pricing should be relatively consistent, and volume will drive the performance over the quarters.

NUPLAZID 的患者群體主要是醫療保險患者，因此定價不會按季度重置，而是在年底進行一次性重置。因此，我們的總收入與淨收入之間的比率受患者組合影響而每季度可能發生的任何變化的影響，在今年剩餘時間內應該基本保持穩定。正如我們所提到的，將去年第一季與今年第一季進行比較，我們確實進行了一次性的重大調整。但展望未來，定價可能應該相對一致，而銷售將推動各季度的業績。

Great. Thank you.

偉大的。謝謝。

Ash Verma, UBS.

瑞銀的 Ash Verma。

Okay, so congrats on the progress. I wanted to ask about the pipeline. So maybe just on carbetocin, so the prior attempt by Levo Therapeutics had failed on the high dose but successful on the low dose. And typically, you generally don't see inverse dose relationship. What makes you confident that the low dose can generate positive data and be accepted by the FDA. And then just secondly, any thoughts on GLP-1 using Prader-Willi? Thanks.

好的，恭喜你有進展。我想詢問有關管道的情況。所以可能只是卡貝縮宮素，所以 Levo Therapeutics 之前的嘗試在高劑量上失敗了，但在低劑量上成功了。通常情況下，你一般不會看到反劑量關係。是什麼讓您有信心低劑量可以產生積極的數據並被 FDA 接受。其次，您對 GLP-1 使用 Prader-Willi 有何看法？謝謝。

Thanks, Ash. I think Liz is going to answer both of those for you.

謝謝，阿什。我認為 Liz 會為您解答這兩個問題。

Yes, indeed. Thanks, Ash. So exactly as you say, there was a prior Phase 3 trial that was run that had two doses, a 3.2-milligram dose and a 9.6-milligram dose. The 9.6-milligram dose didn't show statistical separation from placebo. The 3.2-milligram dose did appear to separate from placebo, though of course that was only nominally statistically significant.

是的，確實如此。謝謝，阿什。如您所說，先前進行的第 3 階段試驗有兩種劑量，分別為 3.2 毫克劑量和 9.6 毫克劑量。9.6 毫克劑量與安慰劑無統計學差異。3.2 毫克劑量確實似乎與安慰劑有區別，儘管這當然只是名義上的統計意義。

So as you take a step back, when we think about this, there are a few things that give us confidence in the need to run a second trial with a 3.2-milligram dose and why that's a sensible thing to do. The first of this is that there is mechanistic reason to think that oxytocin and therefore carbetocin is going to be relevant in Prader-Willi. The second piece is that as we look at that 3.2-milligram dose data set, we do see some signs of internal consistency, so positivity at more than one time point and positivity on more than one endpoint.

所以，當你退一步思考這個問題時，有幾件事讓我們有信心以 3.2 毫克的劑量進行第二次試驗，以及為什麼這是明智之舉。首先，有機械性原因認為催產素和卡貝縮宮素與普拉德-威利症候群有關。第二點是，當我們查看 3.2 毫克劑量資料集時，我們確實看到了一些內部一致性的跡象，因此在多個時間點和多個終點上都表現出陽性。

That helps give some additional reassurance about the consistency of that data set and the likelihood that it represents truth. And then finally, I'm always looking for an alternative explanation. Exactly as you say, the inverse dose response is not your typical thing, but it does happen, and there needs to be an explanation as to why that might be the case.

這有助於進一步保證該資料集的一致性以及它代表真實情況的可能性。最後，我一直在尋找另一種解釋。正如您所說，逆劑量反應不是典型現象，但確實會發生，並且需要解釋為什麼會發生這種情況。

It's not possible to prove ultimately with the data that we currently have in hand, but there is a good rationale for the idea that off-target impact at the vasopressin receptor could have the effect of essentially obscuring the ability to see an improvement on hyperphagia and that you get more of that at the higher dose. It's a plausible hypothesis as to how we could have gotten that dose response, and we take all those other pieces of information to pull together to give us some confidence in running this trial and in the likelihood that 3.2 milligrams is going to be useful.

我們目前掌握的數據無法最終證明這一點，但有充分的理由證明，加壓素受體的脫靶影響可能會從本質上掩蓋對暴食症改善的效果，而高劑量服用則能獲得更多的暴食症。關於我們如何獲得該劑量反應，這是一個合理的假設，我們將所有其他資訊匯總在一起，使我們對進行這項試驗有信心，並且相信 3.2 毫克可能會有用。

And then I apologize, I forgot to write down, wait the second -- the GLP-1s. So the data on GLP-1s, there is some use of it within Prader-Willi. There certainly aren't definitive studies that make it clear that it is useful in this patient population. So I would say the jury is still pretty out on whether GLP-1s are helpful for patients with Prader-Willi.

然後我很抱歉，我忘了寫下來，等待第二個——GLP-1。因此，GLP-1 的數據在 Prader-Willi 中有一些用途。當然，沒有明確的研究表明它對該患者群體有用。因此我想說，對於 GLP-1 是否對普拉德-威利症候群患者有幫助，目前尚無定論。

Thank you.

謝謝。

Charles Duncan, Cantor.

查爾斯鄧肯，領唱者。

Hi, this is Elaine Kim for Charles. Thank you for taking our questions. I just wanted to ask for the Phase 3 COMPASS trial, are there any phenotypic behaviors or patient subsets like genetic subtypes or age groups that are more likely to respond to treatment?

大家好，我是查爾斯的 Elaine Kim。感謝您回答我們的問題。我只是想問一下，對於第三階段的 COMPASS 試驗，是否有任何表型行為或患者亞群（如基因亞型或年齡組）更有可能對治療產生反應？

Thank you. I'll let Liz talk about that as well.

謝謝。我也會讓 Liz 談論這個。

Sure. So I do have to give the caveat here that, of course, the data set we have based on right now is really the prior data set, which is relatively small. That said, with the data that we have to date, we haven't been able to identify patient subsets that are more or less likely to respond to carbetocin. We will get some more information out of this, out of the COMPASS trial. But of course, that is a currently enrolling and currently blinded trial, so I'm not able to answer that right now. But thus far, nothing that clearly identifies for us patients who are more likely or less likely to respond.

當然。所以我必須在這裡提出一個警告，當然，我們現在所基於的資料集實際上是先前的資料集，它相對較小。也就是說，根據我們迄今為止所掌握的數據，我們還無法確定對卡貝縮宮素有反應的可能性更大或更小的患者亞群。我們將從 COMPASS 試驗中獲得更多資訊。但當然，這是一項目前正在招募且目前處於盲態的試驗，所以我現在無法回答這個問題。但到目前為止，還沒有任何方法可以清楚地幫助我們確定哪些患者更有可能或更不可能做出反應。

That makes sense, and congrats on the accelerated enrollment. I just wanted to ask a quick follow-up regarding the R&D Day next month. I understand that you're giving additional details and data across the pipeline programs, but will you be going through each clinical programs individually? I understand that essential tremors joined recently, so what are your -- could you provide additional color in your plans?

這是有道理的，祝賀加速入學。我只是想快速詢問一下有關下個月研發日的問題。我知道您正在提供整個管道項目的更多細節和數據，但您會分別介紹每個臨床項目嗎？我知道最近特發性震顫也加入了進來，那麼您的——您能為您的計劃提供更多資訊嗎？

Liz, just go ahead and jump in here.

莉茲，儘管跳進來吧。

So we do anticipate touching on all of the -- certainly all of the currently clinically staged programs. So we would have a touch on essential tremor in there as well. And we do have some new data that I'm looking forward to sharing on that program in particular.

因此，我們確實期望觸及所有——當然是所有目前處於臨床階段的項目。因此我們也會涉及特發性震顫。我們確實有一些新數據，我期待在該計劃上與大家分享。

Fantastic. Thank you for taking our questions.

極好的。感謝您回答我們的問題。

Thank you.

謝謝。

Marc Goodman, Leerink Partners.

馬克古德曼（Marc Goodman），Leerink Partners。

Hi, good afternoon. This is Basma on for Mark. Thank you for taking our question. We have a question on DAYBUE. Can you provide some color on the utilization rate or the compliance in the quarter? And also, if you can provide some color on the average age and weight of the patient on therapy to date, and whether you see correlation between the age and the discontinuation rate. That's it for us. Thank you.

嗨，下午好。這是巴斯瑪 (Basma) 為馬克 (Mark) 上場的。感謝您回答我們的問題。我們對 DAYBUE 有一個疑問。您能否提供一些有關本季度利用率或合規性的信息？此外，您是否可以提供一些關於迄今為止接受治療的患者的平均年齡和體重的信息，以及您是否看到年齡和停藥率之間的相關性。對我們來說就是這樣。謝謝。

I'm going to let Tom talk to the compliance and any insight on the weight-age correlation.

我打算讓湯姆談談依從性以及對體重與年齡相關性的任何見解。

So in terms of compliance, if you recall in the fourth quarter, we said that our compliance rate was in the low 70% range. It was marginally down in Q1 in the very high 60s. We believe that this is down to primarily customers just becoming more confident in their titration strategies. We are seeing that some patients are actually starting on a lower dose and then moving upwards as they continue with therapy.

因此，就合規性而言，如果您還記得，在第四季度，我們說過我們的合規率在 70％ 以下。第一季略有下降，達到 60 多點。我們認為，這主要是因為客戶對他們的滴定策略變得更有信心。我們發現，有些患者實際上是從較低的劑量開始，然後隨著治療的持續逐漸增加劑量。

And we think that this may actually be contributing to the just ongoing persistency that we're now seeing with new patient starts as well. So encouraging is nothing that we are overly concerned about because our goal is to make sure that every single new patient start that we have is able to continue for the long term and truly see the benefits that we know that DAYBUE offers. So that's what I would say around that.

我們認為這可能實際上導致了我們現在在新患者開始時看到的持續性。我們並不需要過度擔心如此令人鼓舞的事情，因為我們的目標是確保每位新患者都能夠長期堅持下去，並真正看到我們所知道的 DAYBUE 所提供的好處。這就是我要說的。

In terms of our broader patient mix, I mean, it continues to be across a broad range of patients. We have started to see over time some older patients, more mature patients who may not have necessarily been there at the beginning come online. And obviously, they would be slightly heavier in terms of weight banding. Generally speaking, I think the dynamics that we've seen since launch have kind of held relatively stable.

就我們更廣泛的患者組合而言，我的意思是，它仍然涵蓋廣泛的患者。隨著時間的推移，我們開始看到一些年齡較大、更成熟的患者開始上線，而他們一開始可能不一定會在那裡。顯然，從重量範圍來看，它們會稍微重一些。總的來說，我認為自推出以來我們看到的動態一直保持相對穩定。

I think the other part of that question was do we see a dynamic between consistency and age, and I think the answer is we don't actually see anything across the age range in terms of a link between age and persistency.

我認為這個問題的另一部分是我們是否看到了一致性和年齡之間的動態關係，我認為答案是，就年齡和持久性之間的聯繫而言，我們實際上並沒有看到任何跨年齡層的動態關係。

As I mentioned, we're encouragingly -- I think, all of the cohorts that we saw throughout 2024 we've seen improvements in persistency across them all. And I think, again, that gives us great confidence that as we move into '25, we'll be able to continue with that kind of dynamic into the rest of the year.

正如我所提到的，我們感到鼓舞——我認為，我們在 2024 年看到的所有群體都看到了持久性的提高。我認為，這再次給了我們很大的信心，隨著我們進入25年，我們將能夠在今年剩餘的時間裡繼續保持這種活力。

Great. Thanks, Tom. Does that answer your question?

偉大的。謝謝，湯姆。這回答了你的問題嗎？

Yes. Thank you very much.

是的。非常感謝。

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

Hey there, this is Julian on for Paul. Thanks so much for taking our question. I guess another one on trofinetide for ex-US approvals, I guess, what do you guys see as maybe the biggest risk to the approval process? I guess, could you just speak to your confidence in getting EMA approval and eventual reimbursement there?

大家好，我是 Julian，代替 Paul。非常感謝您回答我們的問題。我想還有一個關於曲芬太尼在美國以外獲得批准的問題，我想，你們認為批准過程中最大的風險是什麼？我想，您能否談談您對獲得 EMA 批准並最終獲得報銷的信心？

And then I guess a second quick one is just where does BD fit on your list of priorities this year? Is this mainly about execution under new management, or are you interested in transacting as other executives have mentioned that valuations have come down and biotechs have been reaching out to pharmas for partnership? Thank you.

然後我想第二個快速問題是，BD 在您今年的優先事項清單中處於什麼位置？這主要是為了新管理層的執行，還是您對交易感興趣，因為其他高管提到估值已經下降，生物技術公司一直在與製藥公司尋求合作？謝謝。

Hey, thanks, Julian. I'll start on both of those, and if Liz wants to add in -- in terms of our EMA time clock, it's proceeding as per expectations. We're coming up to our 120-day questions. As you know, we've got approval in both the US and Canada now, so the regulatory team is fairly well apprised of the questions. And we had nothing different or any communication to suggest that we're not proceeding according to the time clock.

嘿，謝謝，朱利安。我將從這兩項工作開始，如果 Liz 想添加的話——就我們的 EMA 時間鐘而言，一切都按預期進行。我們即將開始回答 120 天的問題。如您所知，我們現在已經獲得美國和加拿大的批准，因此監管團隊對這些問題相當了解。我們並沒有發現任何異常情況，也沒有任何通訊顯示我們沒有按照時間表進行。

As and when we get our day 120 questions, we may share a little bit more. But for right now, we're feeling very confident that we're proceeding down the right path. In terms of BD, the question was, are we just going to execute, or are we interested in transacting? I think we are very interested in transacting according to our principles. And as we've shared before, we're looking for exciting assets in areas of higher medical need where we can bring the ACADIA team into the space with confidence that we could commercially launch.

當我們收到第 120 個問題時，我們可能會分享更多。但就目前而言，我們非常有信心我們正沿著正確的道路前進。就 BD 而言，問題是，我們只是要執行，還是我們有興趣進行交易？我認為我們非常有興趣按照我們的原則進行交易。正如我們之前所分享的，我們正在尋找醫療需求更高的領域的令人興奮的資產，我們可以將 ACADIA 團隊帶入該領域，並有信心實現商業化。

And so we're looking for those assets right now. We're actively out there. We remain disciplined in terms of our P&L management and ensuring that we are keeping our P&Ls, as Mark likes to say, pristine. But we are very much looking actively, not only in our and, of course, bases of neuro and neuro rare, but also to reinforce our direction at JPMorgan, where we explained that we've now opened our aperture and are actively looking at rare diseases outside the neuro space, including endocrine, metabolic, cardiovascular, immunology, and other spaces.

因此我們現在正在尋找這些資產。我們正積極地進行工作。我們在損益管理方面保持嚴謹，確保我們的損益保持完美，正如馬克所說的那樣。但我們非常積極地尋找，不僅在我們的神經和神經罕見疾病領域，當然也包括加強我們在摩根大通的方向，我們解釋說，我們現在已經打開了我們的視野，正在積極尋找神經領域以外的罕見疾病，包括內分泌、代謝、心血管、免疫學和其他領域。

So we're excited to continue to look at that and are diligently doing that right now. The market is what the market is. We're actively looking at those compounds against the criteria I've just -- Schneyer, do you want to add anything to that?

因此，我們很高興繼續關注這個問題，並且正在努力做到這一點。市場就是市場。我們正在根據我剛才提出的標準積極研究這些化合物——施奈爾，你想補充什麼嗎？

Yes, I think for us, we're well-positioned to act in the current environment. I think for us, the question when you have swings in valuations, do people on the other side of the table have their expectations reset? And I think for us, if that happens, and we're able to get good strategic deals at good financial value for the company, we're ready to transact and expand the portfolio. And if that hasn't happened, we can stay patient until the right time.

是的，我認為對我們來說，我們已準備好在當前環境下採取行動。我認為，對我們來說，當估值出現波動時，桌子另一邊的人是否會重新設定他們的期望？我認為，對於我們來說，如果發生這種情況，並且我們能夠以對公司有利的財務價值獲得良好的策略交易，我們就準備好進行交易並擴大投資組合。如果這種情況還沒有發生，我們可以耐心等待，直到合適的時機到來。

I hope that answers your question, Julian.

我希望這能回答你的問題，朱利安。

Absolutely.

絕對地。

David Huang, Deutsche Bank.

德意志銀行的 David Huang。

Hi there. Thanks so much for taking my questions. So first on DAYBUE, I just wanted to ask about the persistency you're seeing here long-term at 12 months. I think you mentioned it was a little bit north of 50%. Is there more work to do there? Do you think that can materially improve, or are we kind of more at steady state and it would be more beneficial to focus on net patient ads? And then just with Prader-Willi, your asset versus commercial positioning of Soleno's product, which is now on the market, how do you kind of think about that? Thanks a lot.

你好呀。非常感謝您回答我的問題。因此，首先關於 DAYBUE，我只想問一下您在 12 個月內看到的長期持久性。我認為您提到過它略高於 50%。那裡還有更多工作要做嗎？您認為這能帶來實質的改善嗎？或者我們處於更穩定的狀態，而將重點放在淨患者廣告上會更有利？那麼就普拉德-威利症候群而言，您對目前市場上的 Soleno 產品進行資產定位與商業定位有何看法？多謝。

Great. Thank you for the two-parter, David. I'll let Tom start on that one.

偉大的。謝謝你的兩部分，大衛。我讓湯姆開始做這件事。

Yes, thanks, David. So as we mentioned, yes, our persistency is around 50% after 12 months. We expect that that's going to kind of stay within that ballpark moving forward, so we don't anticipate there's going to be big swings up or down, given the data that we're seeing come through. Just as a reminder as to how we're getting there, I mean, obviously we mentioned we've seen a a nice continuation in terms of the discontinuation story that we showed in Q4 with a 35% improvement in the quarter.

是的，謝謝，大衛。正如我們所提到的，是的，12 個月後我們的堅持率仍在 50% 左右。我們預計，未來這一數字將保持在這個範圍內，因此，根據我們看到的數據，我們預計不會大幅上漲或下跌。只是為了提醒我們是如何實現這一目標的，我的意思是，顯然我們提到，就我們在第四季度展示的停產故事而言，我們看到了良好的延續，本季度改善了 35%。

We believe that that's important as we now really focus all of our efforts on driving new patient starts. And that's been the primary angle and primary focus of the expanded customer model that we mentioned as well. So absolutely, I think you should be thinking about two main factors: new patient starts and active patients because it's going to be the active patients that we believe that we can continue to grow over time that are really going to be meaningful for the ongoing revenue uptick for this brand into the long term.

我們認為這很重要，因為我們現在真正集中所有精力來推動新患者的開始。這也是我們提到的擴展客戶模型的主要角度和主要焦點。所以絕對的，我認為你應該考慮兩個主要因素：新患者開始數量和活躍患者數量，因為我們相信隨著時間的推移，活躍患者數量可以繼續增長，這對於該品牌長期持續的收入增長真正有意義。

Liz, do you want to touch on opposition versus the new Soleno product?

莉茲，你想談談對新款 Soleno 產品的反對意見嗎？

Sure. I'll start out with the fact that we're delighted for the PWS community that there is now a first therapy available for them. That said, I think we see this as an area of significant high unmet need and complex patients who are dealing with a number of different challenges. It's the kind of space where we think that it's likely that there is going to be absolutely room for multiple agents that are used with different MOAs, with different benefit-risk profiles that physicians can use according to the patient that's in front of them. I don't know if there's anything you want to add here, Tom?

當然。首先我要說的是，我們為 PWS 群體感到高興，因為他們現在可以獲得第一種治療方法。話雖如此，我認為我們認為這是一個存在大量未滿足需求且患者情況複雜的領域，他們需要應對許多不同的挑戰。我們認為，在這種領域中，絕對有空間容納多種具有不同 MOA、具有不同獲益風險特徵的藥物，醫生可以根據他們面前的患者情況使用這些藥物。我不知道您是否還有什麼要補充的，湯姆？

Well, the only thing I would add is we know that the Prader-Willi population, they have very complex and distinct needs, and we actually believe that there's going to be an opportunity for more than one product to play here. And I think with therapeutic areas like this the notion of combination therapy could also be something that plays out into the future as well. So a pretty substantial patient population here in the US, plenty of opportunity for more than one player to play, and we will be ready to launch should the data be positive.

好吧，我唯一想補充的是，我們知道普拉德-威利症候群患者有非常複雜和獨特的需求，我們確實相信，不只一種產品可以在這裡發揮作用。我認為，在這樣的治療領域，聯合治療的概念也可能在未來發揮作用。因此，美國的患者群體相當龐大，為多個參與者提供了充足的參與機會，如果數據是積極的，我們將準備好啟動該計畫。

Yes, and we do spend a lot of time, of course, talking to caregivers, advocacy organizations, and we hear pretty robustly that, again, they are delighted that there is something available for their family members now. And they absolutely think that there needs to be continued therapies and the ability to treat an individual patient for their individual purposes.

是的，當然，我們確實花了很多時間與護理人員、倡導組織交談，我們再次聽到他們非常高興，因為他們的家人現在可以得到一些幫助了。他們確實認為需要持續治療，並有能力根據個別患者的具體情況進行治療。

Thanks, guys. Hopefully that answers the question, David.

謝謝大家。希望這能回答這個問題，大衛。

Yes, thank you.

是的，謝謝。

Sean Lehmann, Morgan Stanley.

摩根士丹利的肖恩·萊曼。

Hi, good afternoon. This is Catherine on for Sean. Thank you so much for taking our question. Just one from us on your earlier pipeline. For ACP-711, you announced the successful completion of the Phase 1 MAD cohorts earlier this year. We're just curious if you can provide any color on what you observed here and if you have an update on the status of that study, thank you.

嗨，下午好。我是凱瑟琳，代替肖恩。非常感謝您回答我們的問題。我們僅就您先前的管道提出一個問題。對於 ACP-711，您在今年稍早宣布成功完成第一階段 MAD 隊列研究。我們只是好奇您是否可以提供任何關於您在這裡觀察到的內容的信息，以及您是否有關於該研究狀態的最新消息，謝謝。

Yes, so I think what I'd share there is consistent with what we put out at the time, we were pleased with the safety and tolerability profile we were seeing in that study. There are some interesting pieces on the biomarker side that we'll be sharing at R&D Day, so please feel free to come in and look for that. Status-wise, we're continuing forward with additional explorations that we think are necessary to get us lined up for the Phase 2 that we're planning to start in 2026. So continued good progress there.

是的，所以我認為我所分享的內容與我們當時發布的內容一致，我們對在研究中看到的安全性和耐受性狀況感到滿意。我們將在研發日分享一些有關生物標誌物的有趣內容，請隨時進來查看。從現狀來看，我們將繼續進行我們認為必要的額外探索，為我們計劃於 2026 年開始的第二階段做好準備。因此那裡繼續取得良好進展。

Thanks, Catherine.

謝謝，凱瑟琳。

Tazeen Ahmad, BofA Securities.

Tazeen Ahmad，美國銀行證券。

Hi, good afternoon. Thanks for taking my question. For trofinetide in EU, can you maybe, Catherine, give us a sense on in what ways the launch could be different from the trajectory that DAYBUE has seen in the US? I know you bring a lot of experience from launching products outside of the US. What kind of attention to specifics should we be paying as we think about how to model out European launches for your drugs and how we think about DAYBUE in general.

嗨，下午好。感謝您回答我的問題。對於歐盟的曲菲奈肽，凱瑟琳，您能否告訴我們，此次推出的產品與 DAYBUE 在美國的發展軌跡有何不同？我知道您在美國以外推出產品方面擁有豐富的經驗。當我們思考如何為您的藥品製定歐洲上市模型以及我們如何看待 DAYBUE 時，我們應該關注哪些具體細節。

Yes, thanks, Tazeen. So let me start with the European overall population being larger than the US. So we are -- but that is sort of in line with countryside. So there's no specific country that has more or less patients. So as you know, Germany being the largest country in the EU, we will launch first into Germany. As you know, there's a period of free pricing, and then after that, we start to negotiate with AMNOG. And then beyond that, we'll look at each of the countries and start those negotiations with the national payers.

是的，謝謝，Tazeen。首先我要說的是，歐洲的總人口比美國多。確實如此——但這與鄉村的風氣很相符。因此，沒有哪個國家的患者人數更多或更少。如你所知，德國是歐盟最大的國家，我們將首先進入德國。如您所知，有一段時間的自由定價，之後我們開始與 AMNOG 進行談判。除此之外，我們也會關注每個國家，並與國家付款人開始談判。

Yes, both Tom and I have our experience at launching in Europe. We also have now put in place a really great team who have a lot of rare experience in Europe, and we're building up our dossiers. We're building up our value story, and we're ready to start those discussions with the authorities as soon as we get that regulatory approval.

是的，湯姆和我都有在歐洲開展業務的經驗。我們現在也組建了一支非常優秀的團隊，他們在歐洲擁有豐富的罕見經驗，我們正在累積我們的檔案。我們正在建立我們的價值故事，並準備在獲得監管部門批准後立即與當局開始討論。

I think to your point about learning from the US launch, as with all global launches, the launch country, which generally tends to be the US, is the one where we can learn a lot. And I think we have learned about the importance of working with families and the importance making sure that we really are sharing the titration strategies that have been put in place here. So there's a lot of work going on right now with the KOL communities, with the advocacy groups.

我認為，正如您所說的從美國產品的發布中吸取的教訓一樣，與所有全球產品的發布一樣，發布國家（通常是美國）是我們可以學到很多東西的國家。我認為我們已經了解了與家庭合作的重要性，以及確保我們真正分享這裡實施的滴定策略的重要性。因此，目前我們正在與 KOL 社區和倡導團體進行大量工作。

We had a big bolus of patients in the US that came out the gate pretty strong. We're also getting a lot of inquiries from patients in the European Union, and that's why we put in place our main patient program and our managed access program for those physicians that want to access trofinetide in the countries where it is legally and regulatory allowed. Those processes will be in place. We don't expect sort of the same sort of massive bolus of patient dynamic, but each country is going to be slightly different depending on how many of their patients are on those managed access programs.

我們在美國接待了大批患者，他們的病情都十分嚴重。我們也收到了許多來自歐盟患者的諮詢，因此我們為那些希望在合法且監管允許的國家使用曲菲奈肽的醫生製定了主要患者計劃和管理訪問計劃。這些流程將會到位。我們並不期望出現相同類型的大量患者動態，但每個國家的情況會略有不同，具體取決於有多少患者參加了這些管理訪問計劃。

We feel very confident that we understand what we're doing, we understand how to get our product into the market, and we're also investing appropriately. We're not investing all over the place. We're being very strategic about where we build our teams, about where we put our people, and we will take into account any future administration directives that affect that, too. We're very conscious about it, but also very excited, and mostly excited by the advocacy groups who are very, very interested in accessing trofinetide for their loved ones. Thanks, Tazeen, for the question.

我們非常有信心，我們了解我們在做什麼，我們知道如何將我們的產品推向市場，我們也在進行適當的投資。我們不是到處投資。我們對在哪裡組建團隊、在哪裡安置員工都非常有策略性，我們也會考慮任何影響這些的未來管理指令。我們對此非常清楚，但也非常興奮，最讓我們興奮的是那些非常非常有興趣為他們的親人獲得曲非奈肽的倡導團體。謝謝 Tazeen 提出這個問題。

Gregory Renza, RBC Capital Markets. Your line is now open.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。您的線路現已開通。

Hi, Catherine and team. It's Anish on for Greg. Congrats on the progress this quarter, and thanks for taking our questions. Firstly, as a follow on to David's previous question, what unique aspects of your commercial engine or priorities within the target market do you believe you'll be able to leverage to rise above competitors in the PWS market with respect to Soleno and other therapies in development?

嗨，凱瑟琳和她的團隊。阿尼什 (Anish) 取代格雷格 (Greg)。恭喜本季的進展，並感謝您回答我們的問題。首先，作為對 David 先前問題的延續，您認為您可以利用您在商業引擎中的哪些獨特方面或目標市場中的優先事項，在 PWS 市場上超越 Soleno 和其他正在開發的療法的競爭對手？

And secondly, obviously, there's a lot of concern across the sector on macro and policy exposure for companies. I know you commented on inventory already, but maybe if you could just share some thoughts around where DAYBUE and NUPLAZID might be impacted along their respective supply chains and how you're navigating that. Thanks so much.

其次，顯然整個產業都非常關注公司面臨的宏觀和政策風險。我知道您已經對庫存發表了評論，但也許您可以分享一些想法，關於 DAYBUE 和 NUPLAZID 在各自的供應鏈中可能受到哪些影響，以及您如何處理這些問題。非常感謝。

Great. Thanks, Anish. Quite a few different subsets of questions there. So let me start by just giving you an overview of my thoughts around the commercial engine. I'll ask Tom to add, and then we'll throw it to Mark to talk about supply chain and tariffs. So just in terms of commercial engine we have a very strong team now, both in neuropsych and in rare, who understand the subtleties of launching within a rare space. And we've learned a lot through the DAYBUE launch. So we feel very well prepared as a company to work within the Prader-Willi community.

偉大的。謝謝，阿尼什。那裡有相當多不同的問題子集。首先，我先概述一下我對商業引擎的看法。我會讓湯姆補充，然後我們會把它交給馬克討論供應鏈和關稅。因此，就商業引擎而言，我們現在擁有一支非常強大的團隊，既有神經心理學方面的，也有罕見領域的，他們了解在罕見空間內發射的微妙之處。透過 DAYBUE 的發布，我們學到了很多。因此，作為一家公司，我們感到非常有準備，可以在普拉德-威利症候群患者群體中開展工作。

We have strong associations with them already. We have our teams out there right now. And as Liz has already outlined, we feel very strongly that the community is asking for as many options as possible for their patients. These are complicated, complex patients. And we'll see over time the need, I believe, for more than one therapy option for sure. So we feel very confident in our ability to go out there and compete but also offer patients choices which we believe are very important. Tom, is there anything you'd bring from your previous experience in rare?

我們已經與他們建立了牢固的聯繫。我們現在就派出我們的團隊前往那裡。正如 Liz 已經概述的那樣，我們強烈感覺到社區正在要求為患者提供盡可能多的選擇。這些都是非常複雜的病人。我相信，隨著時間的推移，我們肯定會需要多種治療方案。因此，我們對自己在市場上競爭的能力非常有信心，同時也為患者提供我們認為非常重要的選擇。湯姆，你從以前在稀有領域的工作經驗中能學到什麼嗎？

Yes, I mean, I would say that clearly, we have already launched a RARE product in very recent history, the DAYBUE. I think we've learned a great deal as we've gone through that launch. And as Catherine mentioned, I think both Catherine and I have had the privilege of launching products in other rare spaces.

是的，我的意思是，我可以明確地說，我們最近已經推出了一個罕見的產品，DAYBUE。我認為我們在這次發布過程中學到了很多。正如凱瑟琳所提到的，我認為凱瑟琳和我都有幸在其他罕見領域推出產品。

And I think being able to continue to kind of build that muscle, make sure that we're pulling through the experiences that we have, and really making sure that as the 101 data reads out that we're able to leverage the product profile in an appropriate way as quickly as possible, taking all of the learnings that we already have but also thinking about some of the kind of unique aspects that we bring as ACADIA with a true kind of focus on the patient and on patient advocacy, I think we will have a significant leg up in making sure that we can be highly competitive even as a fast follow.

我認為，能夠繼續增強這種實力，確保我們能夠汲取已有的經驗，真正確保在 101 數據讀取出來後，我們能夠盡快以適當的方式利用產品概況，汲取我們已有的所有經驗，同時也考慮到我們作為 ACADIA 所帶來的一些獨特方面，真正關注患者和患者權益，我認為我們將在確保我們能夠快速跟進的同時保持高度優勢。

Mark, do you want to talk about the supply chain?

馬克，你想談談供應鏈嗎？

On the supply chain, obviously, we're monitoring all the events of the day as it relates potentially to tariffs that may come forth for the industry. I think as our supply chain is set up today, our API for both products is manufactured outside the US. The [ABU] has drug product manufacturing in Canada and the US. The drug product manufacturing for NUPLAZID is all in the US. I think what we've done thus far in recent months, as I mentioned in the call, was onshore as much inventory as possible.

在供應鏈上，顯然我們正在監控當天的所有事件，因為它可能與該行業可能出現的關稅有關。我認為，隨著我們今天供應鏈的建立，這兩種產品的 API 都是在美國境外生產的。[ABU] 在加拿大和美國擁有藥品生產基地。NUPLAZID 的藥品生產全部在美國進行。我認為，正如我在電話中提到的那樣，我們近幾個月來所做的就是盡可能在國內儲存庫存。

Due to investments that the company had made previously in advance of potential DRP approval, the company did make investments in inventory for supply for [pimavanserin], which is why we have the supply. All of that's in the United States today and can last us into the mid to late 2030s. And we don't own any manufacturing sites. We don't have any infrastructure that's set up with our supply. Like everybody, we look at our supply chain to make sure we have assurances of supply, redundancy, high quality suppliers, appropriate price.

由於公司在獲得潛在 DRP 批准之前已經進行過投資，因此公司確實對 [pimavanserin] 的供應庫存進行了投資，這就是我們有供應的原因。所有這些現在都存在於美國，並且可以持續到2030年代中後期。我們沒有任何生產基地。我們沒有任何與我們的供應相關的基礎設施。像所有人一樣，我們專注於我們的供應鏈，以確保我們有供應、冗餘、高品質的供應商和合適的價格的保證。

If there are tariffs, that's one cost that will be considered in the overall supply chain. But from a manufacturing standpoint, time and investment can change everything. So nothing's permanent, but nothing changes overnight. I think we feel very comfortable in the position that we are today with our inventories and we'll keep the supply chain as is until there's an appropriate reason, whatever that may be, to change it. We can do that in the future.

如果有關稅，這是整個供應鏈中需要考慮的一項成本。但從製造業的角度來看，時間和投資可以改變一切。所以沒有什麼是永恆不變的，但也沒有什麼會在一夜之間改變。我認為我們對目前的庫存狀況感到非常滿意，並且我們將保持供應鏈現狀，直到有適當的理由（無論是什麼理由）來改變它。我們將來可以做到這一點。

Thank, Mark.

謝謝，馬克。

Yatin Suneja, Guggenheim.

古根漢美術館的亞廷·蘇內賈（Yatin Suneja）。

Hey, guys. Thank you for taking my question. A question on the Prader-Willi study. Are you able to talk about the powering of the study and the size of the study to be robust? What effect size are you powered for? What is the minimum you are able to achieve? Thank you.

嘿，大家好。感謝您回答我的問題。關於普拉德-威利研究的一個問題。您能否談談這項研究的動力和研究規模是否穩健？您能獲得多大效果？您至少能夠實現什麼目標？謝謝。

I'll ask Liz to talk about the effect size and the powering for our study.

我會請 Liz 談談我們研究的效果大小和動力。

Yes, so I think, probably, the most important thing to orient here is that we have a study that is substantially larger than the prior study where there was nominal significance, but where if 3.2 had been run by itself, we would have anticipated having a significant p-value. So that is a check in our column.

是的，所以我認為，可能這裡最重要的一點是，我們有一個比之前的研究規模大得多的研究，該研究具有名義上的重要性，但如果 3.2 單獨運行，我們就會預期會有一個顯著的 p 值。這就是我們專欄中的一個檢查。

As far as we think about the specifics of the powering that underlies this, we actually looked at a number of different potential powering scenarios to make sure that we were adequately covered for a few possibilities. The one that is most obviously disclosed is a slight increase in terms of the delta between placebo and active, and that's reflective of the fact that we have a slightly longer time point in this trial than we did in the prior study. But I think broadly consistent expectations with what we've seen historically and a number of different scenarios that get us with strong 80-plus percent powering.

就我們對此背後的供電細節的思考而言，我們實際上研究了許多不同的潛在供電場景，以確保我們充分考慮到一些可能性。最明顯的是，安慰劑和活性藥物之間的差異略有增加，這反映了我們在這次試驗中的時間點比之前的研究稍長。但我認為，這與我們的歷史記錄和許多不同情境的預期大致一致，這些情境使我們獲得了 80% 以上的強勁供電率。

Thanks, Liz. Thanks for the question.

謝謝，莉茲。謝謝你的提問。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi, thanks for taking the question. It's a little bit of a math question on DAYBUE and the ability to find new patients starts faster than patients discontinue. And I guess it's in the context of you're getting close to a thousand patients on therapy in a quarter now. And then a discontinuation or a persistency rate at 12 months of about 50%. So putting those numbers together, I guess the question is, would that mean to expect about 500 patients dropping off over the course of a year? And then if so, how realistic is it to be able to find 500-plus patients of new starts to be able to replace that?

你好，謝謝你回答這個問題。這有點像 DAYBUE 上的一道數學問題，尋找新病患的速度比病患停止治療的速度還要快。我想這是因為你現在每季都會有將近一千名患者接受治療。12 個月時的停藥率或持續率約為 50%。所以把這些數字放在一起，我想問題是，這是否意味著預計一年內會有大約 500 名患者退出？那麼，如果是這樣，找到 500 多名新患者來取代這些患者現實嗎？

Let me try and reorient the math a bit, and if I get convoluted, somebody can help simplify. But you're right, in terms of the patients actively shipped in the quarter, 954. Now of those patients, 65% of them, just above actually, have been on therapy for more than a year. So it's important to understand that within that 954, there are different cohorts of patient start times, but more than 65 have been on the product for over a year.

讓我嘗試重新調整數學，如果我感到困惑，有人可以幫忙簡化。但您說得對，就本季積極運送的患者而言，共有 954 人。目前，這些患者中，有 65%（實際上略高於 65%）已經接受治療一年多了。因此，重要的是要了解，在這 954 名患者中，患者的開始治療時間有所不同，但超過 65 名患者已經使用該產品一年多了。

We continue to see strong persistency beyond a year, so we're not seeing sort of a sudden drop-off beyond that either. So it's really a cohort question, if I may, in terms of the math, Joel, and in terms of new starts added every quarter and the expected time that that patient stays on therapy. Again, we've given you the 12 months if you like, persistency rate. However, we are seeing patients stay on therapy for much longer than that. So that's sort of maybe a way to think about it. Mark or Tom, if you --

我們繼續看到一年後強勁的持久性，因此我們也沒有看到一年後突然的下降。因此，如果可以的話，就數學而言，喬爾，以及就每季度增加的新開始以及該患者接受治療的預期時間而言，這實際上是一個隊列問題。再次，如果您願意的話，我們為您提供了 12 個月的堅持率。然而，我們看到患者接受治療的時間比這要長得多。這也許是一種思考方式。馬克或湯姆，如果你--

When you talk about 12 months, that's the first 12 months of therapy. It's not each 12 months of therapy. So the rate of -- the persistency rates are very high after the curve is like plateauing after as you get out in time. So it's really in that first 12 months that we keep more than 50% of our patients. And then beyond that time, it's a very high rate of persistency. So as Catherine mentioned, we have that stable base of patients that are on therapy more than 12 months, 65% of our current patients. And so then we're adding patients on top of that, and that's how the patient count grows over time.

當你談到 12 個月時，那就是治療的前 12 個月。這不是每年一次的治療。因此，曲線之後的持久率非常高，就像您及時退出後達到穩定狀態一樣。因此，實際上在前 12 個月，我們保留了 50% 以上的患者。在那段時間之後，它的持久性非常高。正如凱瑟琳所提到的，我們擁有接受治療超過 12 個月的穩定患者群，占我們現有患者的 65%。因此，我們在此基礎上不斷增加患者，這就是患者數量隨著時間的推移而增長的方式。

Maybe I'll just give you one statistic that gives you maybe a thought. as we went through 2024, we started sort of with 870 or so patients per quarter, and now we're at 954. So again, they don't drop off just at the end of the year. They continue to stay on therapy. Hoping that that helps you out, Joel. If you need some more follow up, I'm happy to do that too.

也許我只需給你一個統計數據就能讓你有所思考。到 2024 年，我們每季接待的患者數量約為 870 名，而現在已達到 954 名。所以，他們不會在年底就減少。他們繼續接受治療。希望這對你有幫助，喬爾。如果您需要更多跟進，我也很樂意這樣做。

Sumant Kulkarni, Canaccord Genuity.

Sumant Kulkarni，Canaccord Genuity。

Good afternoon. Thanks for taking our questions. I have two quick ones. Given post-trial briefing is done on the pimavanserin-2 case, could you remind us of your latest assumptions on when you might expect generic competition on NUPLAZID? And second, on trofinetide, do you expect to start recognizing European revenue from France via the paid early access program that country allows? And how important might that type of initiative be to give you a good sense of how the product might launch in the rest of Europe.

午安.感謝您回答我們的問題。我有兩個簡短的。鑑於已經對 pimavanserin-2 案進行了庭後簡報，您能否提醒我們您對何時可能出現 NUPLAZID 仿製藥競爭的最新假設？其次，關於曲芬太尼，您是否預計透過該國允許的付費早期訪問計劃開始從法國確認歐洲收入？這種舉措對於讓您了解該產品在歐洲其他地區的推出情況有多重要？

Okay, I'm going to ask Mark to update you on NUPLAZID, and then I'll take the front question.

好的，我將請馬克向您介紹 NUPLAZID 的最新情況，然後我會回答前面的問題。

Yes, so on pimavanserin and IP, we remain kind of in the view that we have bookends, right? The short end of the bookend would be October 2030. The long end of the bookend is February 2038. Really, nothing has changed with our reasoning behind that as we've been talking over the last months and year, whatever the timeframe would be. Really, the only update since the last time we've talked publicly is that oral arguments for the appeal on our composition of matter is now scheduled for June 6 of this year.

是的，所以對於匹莫範色林和 IP，我們仍然認為我們有書擋，對嗎？最短的期限是 2030 年 10 月。書擋的長端是 2038 年 2 月。事實上，無論時間框架如何，我們在過去幾個月和一年中一直在談論的背後的理由都沒有改變。實際上，自從我們上次公開談話以來，唯一的最新消息是，針對我們案件組成上訴的口頭辯論現定於今年 6 月 6 日進行。

In terms of France, I'll start, and Tom can add color. I think you're referring to the ATU program in France, which has now got a different acronym that's currently escaping me. But essentially, it's the early access program where the French government pays for product. We're putting in place mechanisms for that program to be activated in France for DAYBUE. There are a number of regulatory and legal considerations we need to put in place before that's action, but that's actively going on right now.

就法國而言，我先開始，湯姆可以添加顏色。我認為您指的是法國的 ATU 計劃，現在它有一個不同的縮寫，我暫時記不清了。但本質上，這是法國政府為產品付費的早期使用計畫。我們正在建立機制，以便在法國為 DAYBUE 啟動該計劃。在採取行動之前，我們需要考慮一些監管和法律問題，但目前正在積極進行中。

As you know, once you then get reimbursement through the Transparency Commission, those patients switch over to paid product from the French government, and that's our current plan. Again, we have to understand what the French situation is nearer to the time, but we are planning for the ATU to be activated this year, and we're planning for those patients to transition over to commercial product once those negotiations have completed. Tom, did I miss anything on your --

如您所知，一旦您透過透明委員會獲得報銷，這些患者就會轉而使用法國政府的付費產品，而這就是我們目前的計劃。再次，我們必須了解法國近期的情況，但我們計劃今年啟動 ATU，並且我們計劃在談判完成後讓這些患者過渡到商業產品。湯姆，我有沒有錯過你的什麼？--

No, I think as it relates to France, that's entirely true. I mean, the other thing I would say is, obviously, Germany, we will be having a managed access program there as well. And actually, Germany, if you recall, will be out the gates pretty significantly ahead of where we are in France.

不，我認為就法國而言，這是完全正確的。我的意思是，我想說的另一件事是，顯然，在德國，我們也將在那裡實施管理訪問計劃。事實上，如果你還記得的話，德國的出場速度將遠遠領先法國。

So I think if you want to kind of have a good kind of barometer as to what's going to be happening in Europe, the German launch will be the one to watch. Because we do anticipate having patients enrolled in that early access program. And as a reminder, on day one, once we have a European approval, they will be able to be switched over to commercial drug with free drug pricing as well. So more to come, but that's how we expect to see things playing out.

因此，我認為，如果你想要對歐洲未來發生的事情有一個良好的晴雨表，那麼德國的發布會將是值得關注的。因為我們確實希望有患者參與該早期訪問計劃。提醒一下，一旦我們獲得歐洲批准，它們將能夠轉換為商業藥品，並且藥品定價也將免費。未來還會有更多，但這就是我們期望看到事情發展的方式。

Okay, that answers the question. We'll take the next one.

好的，這回答了問題。我們將選擇下一個。

Malcolm Hoffman, BMO Capital Markets. Your line is now open.

馬爾科姆·霍夫曼，BMO資本市場。您的線路現已開通。

Hi, Malcolm on for Evan from BMO. I wanted to touch on NUPLAZID gross net. I believe you said gross net for the quarter was roughly 24% and the guide suggests a range for the year of 22.5% to 25.5%. Can you just talk through what pushes and pulls you expect can move this gross net one side or another of the guide? Thank you.

大家好，我是 Malcolm，取代 BMO 的 Evan。我想談談 NUPLAZID 的總淨值。我相信您說過本季的毛淨利率約為 24%，而指南建議全年的利率範圍為 22.5% 至 25.5%。您能否簡單談談您認為什麼樣的推拉因素能夠將這張大網移到導軌的一側或另一側？謝謝。

Yes, I'll let Mark take the gross net question.

是的，我請馬克回答總淨值問題。

Yes, I think right now, at least the first quarter is kind of right in the middle of our guidance. It really is just patient mix, which we don't control. It's just the payers for our patient base can change over time, and that can influence quarterly fluctuations, and what the gross to net is on the year. The other thing that influences it is if we take any pricing action. We had a small, modest price increase at the beginning of the year. We don't foreshadow when we may or may not take pricing action. We price our medicines to value, and we just announce that when and if we do it over time.

是的，我認為現在至少第一季的業績正處於我們的預期之中。這其實只是病人的混合，我們無法控制。只是我們患者群體的付款人可能會隨著時間而變化，這可能會影響季度波動以及全年的毛收入與淨收入之比。影響它的另一個因素是我們是否採取任何定價行動。今年年初，我們的價格出現了小幅上漲。我們不會預示何時會採取或不會採取定價行動。我們根據價值對藥品進行定價，並且只有在我們隨著時間的推移做出決定時才會公佈。

Great. Thanks, Mark.

偉大的。謝謝，馬克。

Thank you. I'm showing no further questions at this time. I would now like to turn it back to Catherine Owen Adams for closing remarks.

謝謝。我目前沒有其他問題。現在我想請凱瑟琳·歐文·亞當斯作最後發言。

Thanks, everybody, for your questions this quarter. We look forward to continuing to deliver on our commitments to our patients and updating you on our progress next quarter. Thanks again for your questions.

感謝大家本季提出的問題。我們期待繼續履行對患者的承諾，並在下個季度向您通報我們的進展。再次感謝您的提問。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝大家參加今天的會議。該計劃確實就此結束。您現在可以斷開連線。