ACADIA Pharmaceuticals Inc (ACAD) 2023 Q1 法說會逐字稿

Good day, ladies and gentlemen. Thank you for standing by. Welcome to ACADIA Pharmaceuticals First Quarter 2023 Financial Results Conference Call. My name is Corey, and I will be your coordinator for today.(Operator Instructions)

女士們先生們，美好的一天。謝謝你的支持。歡迎來到 ACADIA Pharmaceuticals 2023 年第一季度財務業績電話會議。我的名字是科里，今天我將擔任您的協調員。（操作員說明）

Please be advised today's conference call is being recorded. I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at ACADIA. Please proceed.

請注意，今天的電話會議正在錄製中。我現在想將演示文稿轉交給 ACADIA 投資者關係副總裁 Mark Johnson。請繼續。

Thank you. Good afternoon, and thank you for joining us on today's call to discuss ACADIA's first quarter 2023 financial results. Joining me on the call today from ACADIA are Steve Davis, our Chief Executive Officer, who will provide an overview of our performance and review of our business; Brendan Teehan, our Chief Operating Officer, Head of Commercial, will provide updates on our recent launch of DAYBUE for the treatment of Rett syndrome followed by commercial updates on our NUPLAZID franchise; Doug Williamson, our Head of R&D, will provide an update of our pipeline programs, and Mark Schneyer, our Chief Financial Officer, will discuss our financial results before turning it back to Steve for final remarks and opening the call up for your questions. In addition, Kathie Bishop, our Chief Scientific Officer and Head of Rare Disease, will be on the call and available for the Q&A session.

謝謝。下午好，感謝您參加今天的電話會議，討論 ACADIA 2023 年第一季度的財務業績。我們的首席執行官史蒂夫·戴維斯 (Steve Davis) 今天和我一起參加了 ACADIA 的電話會議，他將概述我們的業績和對我們業務的審查；我們的首席運營官兼商業主管 Brendan Teehan 將提供我們最近推出的用於治療 Rett 綜合徵的 DAYBUE 的最新信息，然後是我們 NUPLAZID 特許經營權的商業更新；我們的研發主管 Doug Williamson 將提供我們管道計劃的最新情況，我們的首席財務官 Mark Schneyer 將討論我們的財務結果，然後再將其返回給 Steve 進行最後評論並開始徵求您的問題。此外，我們的首席科學官兼罕見病負責人 Kathie Bishop 將隨叫隨到並參加問答環節。

I would also like to point out that we are using supplemental slides, which are available on the Events and Presentations section of our website. Before we proceed, I would first like to remind you that during our call today, we will be making a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements, including goals, expectations, plans, prospects, growth potential, timing of events or future results are based on current information, assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially. 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.

我還想指出，我們正在使用補充幻燈片，這些幻燈片可在我們網站的“活動和演示”部分找到。在我們繼續之前，我想首先提醒您，在我們今天的電話會議中，我們將根據 1995 年《私人證券訴訟改革法案》做出一些前瞻性陳述。這些前瞻性陳述，包括目標，預期、計劃、前景、增長潛力、事件發生時間或未來結果基於當前信息、假設和預期，這些信息、假設和預期本質上會發生變化，並涉及許多可能導致實際結果大不相同的風險和不確定性。這些因素和與我們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。請注意不要過分依賴這些前瞻性陳述，這些陳述僅在今天發布。

I'll now turn the call over to Steve.

我現在將電話轉給史蒂夫。

Thank you, Mark. Good afternoon, everyone, and thank you for joining us today.

謝謝你，馬克。大家下午好，感謝您今天加入我們。

Please turn to Slide 5. 2023 is off to a great start with strong progress across our 4 strategic priorities: First, in March, DAYBUE received FDA approval as the first and only treatment for Rett syndrome. Our team moved quickly to make DAYBUE of commercially available by mid-April, and we will be sharing updates on our launch execution with you today.

請轉到幻燈片 5。2023 年是一個良好的開端，我們的 4 個戰略優先事項取得了長足進展：首先，3 月，DAYBUE 獲得 FDA 批准，成為 Rett 綜合徵的第一個也是唯一一個治療方法。我們的團隊迅速採取行動，在 4 月中旬之前將 DAYBUE 推向市場，我們今天將與您分享我們發布執行的最新情況。

Second, we continue to deliver steady volumes in our NUPLAZID franchise in Parkinson's disease psychosis. Our PDP business has generated increasing cash flows year-over-year every year since turning profitable in 2019.

其次，我們繼續在帕金森病精神病的 NUPLAZID 特許經營中提供穩定的數量。自 2019 年扭虧為盈以來，我們的 PDP 業務每年產生的現金流量都在逐年增加。

Third, we expect to complete enrollment for our Phase III study, ADVANCE-2, evaluating pimavanserin as a treatment for the negative symptoms of schizophrenia around midyear, and we'll have top line results early in 2024.

第三，我們預計將在年中左右完成 III 期研究 ADVANCE-2 的註冊，評估匹莫萬色林作為治療精神分裂症陰性症狀的藥物，我們將在 2024 年初獲得一線結果。

And fourth, we've completed Phase I development of ACP-204, part of our next-generation 5-HT2A program. Our next steps are to meet with the FDA to discuss the clinical development plan to evaluate ACP-204 as a treatment for Alzheimer's disease psychosis.

第四，我們已經完成了 ACP-204 的第一階段開發，這是我們下一代 5-HT2A 計劃的一部分。我們的下一步是與 FDA 會面，討論臨床開發計劃，以評估 ACP-204 作為阿爾茨海默病精神病的治療方法。

Let's begin with a quick recap of our DAYBUE approval and subsequent launch on Slide 6. Since the approval of DAYBUE on March 10, we've been working around the clock to deliver this first-ever treatment for Rett syndrome to the patient community. Rett syndrome is an extremely debilitating rare genetic neurodevelopmental disorder that severely impacts the lives of patients and their families. We are beyond excited to be launching this first-in-class first-to-market drug for a disease with such a high unmet need. The treating community is also excited. They've been extremely receptive and HCPs are moving quickly to prescribe DAYBUE having waited a very long time for an FDA-approved therapy.

讓我們首先快速回顧一下我們的 DAYBUE 批准和隨後在幻燈片 6 上的發布。自 DAYBUE 於 3 月 10 日獲得批准以來，我們一直在夜以繼日地工作，以向患者社區提供有史以來第一次治療 Rett 綜合徵的藥物。 Rett 綜合徵是一種極度虛弱的罕見遺傳性神經發育障礙，嚴重影響患者及其家人的生活。我們非常高興能夠推出這種一流的首次上市藥物，用於治療需求如此之高的疾病。治療社區也很興奮。他們非常樂於接受，HCP 正在迅速採取行動開出 DAYBUE 處方，等待 FDA 批准的療法已經很長時間了。

In parallel, we are engaged with payers in our first post-approval discussion. As it's typical with rare disease launches, we anticipate it will take some time for payers to adjudicate the initial prescription requests. As you would expect, we are working diligently with plans to obtain insurance coverage for patients who have prescriptions submitted to our hub. Although we are only 3 weeks into the launch, we are highly encouraged with the response we've seen so far, and Brendan will provide additional color on our launch execution to date.

與此同時，我們在第一次批准後討論中與付款人進行了接觸。由於這是罕見疾病上市的典型情況，我們預計付款人需要一些時間來裁定最初的處方請求。如您所料，我們正在努力製定計劃，為向我們中心提交處方的患者獲得保險。雖然我們距離發布僅 3 週，但我們對迄今為止所看到的反響感到非常鼓舞，Brendan 將為我們迄今為止的發布執行提供額外的顏色。

Now let's turn to NUPLAZID on Slide 7. Our NUPLAZID franchise continues to deliver steady volumes and gained market share in a contracted PDP market. In parallel, we have optimized and reduced our NUPLAZID commercial expense base, which has resulted in a significant increase in profitability for the franchise, providing a meaningful contribution to our overall business. Our first quarter performance of $118.5 million in net sales was driven by a year-over-year increase in demand bottles of 2%.

現在讓我們轉到幻燈片 7 上的 NUPLAZID。我們的 NUPLAZID 特許經營權繼續提供穩定的銷量，並在合同 PDP 市場中獲得市場份額。與此同時，我們優化並減少了 NUPLAZID 的商業費用基礎，這導致特許經營的盈利能力顯著提高，為我們的整體業務做出了有意義的貢獻。我們第一季度的淨銷售額為 1.185 億美元，這得益於需求量同比增長 2%。

Selling volumes were down slightly year-over-year as a result of quarterly inventory fluctuations which Mark will describe further in this session. We're beginning to see early indicators that our discussions with healthcare providers on the real-world evidence publications are gaining initial traction. This is evidenced by an increase in our market share of new-to-therapy patients for PDP.

由於季度庫存波動，馬克將在本次會議中進一步描述，銷量同比略有下降。我們開始看到早期跡象表明，我們與醫療保健提供者就真實世界證據出版物進行的討論正在獲得初步關注。 PDP 新治療患者的市場份額增加證明了這一點。

As we've laid out previously, there are 2 catalysts, which we believe can contribute to top line growth for our NUPLAZID franchise: One, as I just mentioned, is the awareness and understanding by healthcare professionals of the 3 real-world studies that demonstrate the benefits of NUPLAZID relative to the off-label atypical antipsychotics. So far, the initial feedback has been very positive on these data sets; and two is a return to growth for Parkinson's medication prescriptions as well as in-person patient visits returning to pre-pandemic levels, which we've not yet observed.

正如我們之前所述，有 2 個催化劑，我們認為它們可以促進我們 NUPLAZID 特許經營的收入增長：一個，正如我剛才提到的，是醫療保健專業人員對 3 項真實世界研究的認識和理解證明 NUPLAZID 相對於標籤外非典型抗精神病藥的益處。到目前為止，對這些數據集的初步反饋非常積極；二是帕金森氏症藥物處方恢復增長，以及患者就診恢復到大流行前水平，這是我們尚未觀察到的。

And now let's briefly review our clinical programs on Slide 8. Doug will provide more detail in his section, but beyond our 2 commercial programs NUPLAZID and DAYBUE. We're developing multiple programs all focused on treating significant needs in CNS. A couple of quick updates. One, as we've noted before, the negative symptoms of schizophrenia has been an exceedingly difficult area with lots of industry [failures] over multiple decades and still no drug approved to treat this condition. With pimavanserin, we've achieved something very rare in this population, a positive pivotal study ADVANCE-1.

現在讓我們在幻燈片 8 上簡要回顧一下我們的臨床項目。Doug 將在他的部分提供更多詳細信息，但不包括我們的 2 個商業項目 NUPLAZID 和 DAYBUE。我們正在開發多個項目，所有項目都專注於治療 CNS 的重大需求。幾個快速更新。第一，正如我們之前所指出的，精神分裂症的陰性症狀一直是一個極其困難的領域，幾十年來有許多行業[失敗]，但仍然沒有藥物被批准用於治療這種情況。借助匹莫範色林，我們在這一人群中取得了非常罕見的成果，即積極的關鍵研究 ADVANCE-1。

So if our ongoing ADVANCE-2 Phase III study results are positive, we would be in a position to submit a supplemental new drug application shortly thereafter. Again, we expect to have results of this study in early 2024. And two, as I mentioned, we've completed our Phase I development work for ACP-204 and the lead molecule in our next-generation 5-HT2A program.

因此，如果我們正在進行的 ADVANCE-2 III 期研究結果是積極的，我們將能夠在此後不久提交補充新藥申請。同樣，我們希望在 2024 年初獲得這項研究的結果。而且，正如我所提到的，我們已經完成了 ACP-204 的第一階段開發工作和我們下一代 5-HT2A 計劃中的先導分子。

The key takeaway here is that the Phase I work continues to support our target product profile, and we plan to initiate Phase II studies in Alzheimer's disease psychosis later this year.

這裡的關鍵要點是，第一階段的工作繼續支持我們的目標產品概況，我們計劃在今年晚些時候啟動阿爾茨海默病精神病的第二階段研究。

I'll now turn it over to Brendan to provide additional insights on our DAYBUE launch execution and NUPLAZID's commercial performance.

我現在將其轉交給 Brendan，讓他提供有關我們 DAYBUE 發布執行和 NUPLAZID 商業表現的更多見解。

Thank you, Steve. Please turn to Slide 10. We are thrilled to have launched our second commercial product, DAYBUE, the first and only medicine ever approved for the treatment of Rett syndrome. As we've discussed throughout the development program, Rett syndrome is a highly debilitating disease with patients requiring lifelong continuous care and assistance with all aspects of daily living. DAYBUE and patient enrollment forms became available on April 17, ahead of our initial expectations. As we are only 3 weeks into the launch, we will not provide any specific metrics today, but we will share initial insights and color on our launch execution and the positive feedback we've received from the broader Rett community.

謝謝你，史蒂夫。請翻到幻燈片 10。我們很高興推出我們的第二個商業產品 DAYBUE，這是有史以來第一個也是唯一一個被批准用於治療 Rett 綜合徵的藥物。正如我們在整個開發計劃中所討論的那樣，雷特綜合症是一種高度衰弱的疾病，患者需要終生持續護理和日常生活各個方面的幫助。 DAYBUE 和患者登記表於 4 月 17 日上市，超出了我們最初的預期。由於距離發布僅 3 週，我們今天不會提供任何具體指標，但我們將分享對我們的發布執行的初步見解和色彩，以及我們從更廣泛的 Rett 社區收到的積極反饋。

Let's turn to Slide 11. First, our launch execution is going very much according to plan. As expected, we are receiving enrollment forms representative of the broad FDA-approved label DAYBUE has received for the treatment of Rett syndrome. With the broad label received back in March, we are pleased to see patient enrollment forms for both male and female Rett patients, both clinical trial participants and de novo patients, patients from all ages above 2 to well above 20 years of age, patients from both clinical trial sites, centers of excellence, high-volume institutions and from stand-alone neurology practices of the identified 4,500 diagnosed and treated Rett patients. As of today, our outreach proactively spans physicians treating well over 50% of the diagnosed Rett population. This includes engagement with 100% of Rett centers of excellence and clinical trial sites, which treat about 25% of the total Rett population.

讓我們轉到幻燈片 11。首先，我們的發布執行非常按計劃進行。正如預期的那樣，我們收到了代表 FDA 批准的廣泛標籤 DAYBUE 已收到的用於治療 Rett 綜合徵的登記表。隨著 3 月份收到的廣泛標籤，我們很高興看到男性和女性 Rett 患者的患者登記表，包括臨床試驗參與者和新患者，所有年齡在 2 歲以上到 20 歲以上的患者，來自臨床試驗地點、卓越中心、大容量機構以及來自已確定的 4,500 名診斷和治療 Rett 患者的獨立神經病學實踐。截至今天，我們的外展活動已經主動涵蓋了治療超過 50% 已確診 Rett 人口的醫生。這包括與 100% 的 Rett 卓越中心和臨床試驗站點合作，這些中心治療約 25% 的 Rett 人口。

In fact, over 90% of our patients remaining from our open-label extension studies have started the process of becoming paid patients. We also have engaged a large number of the 300 high-volume institutions, which represent 60% of the patient population. And we're starting to engage the over 2,700 stand-alone neurology offices in the community setting.

事實上，在我們的開放標籤擴展研究中剩下的患者中有超過 90% 已經開始成為付費患者的過程。我們還與 300 家高容量機構中的大量機構進行了合作，這些機構佔患者人數的 60%。我們開始與社區環境中的 2,700 多個獨立神經病學辦公室合作。

In addition, our launch execution includes development of key marketing materials, both print and digital, standing up and activating a speakers bureau to further educate the Rett treating community, engaging the community at medical congresses, including branded DAYBUE booths. Since approval, we have been actively engaging in a robust and productive dialogue with the payer community and as the process takes time, it's too early to comment further today.

此外，我們的發布執行包括開發關鍵營銷材料（印刷版和數字版）、建立並激活演講局以進一步教育 Rett 治療社區、讓社區參與醫學大會，包括品牌 DAYBUE 展位。自批准以來，我們一直在積極與付款人社區進行強有力且富有成效的對話，由於該過程需要時間，因此今天進一步發表評論還為時過早。

In addition to these payer engagement activities, our ACADIA Connect Support Services hub, along with our field-based family access managers are already providing meaningful support to both HCPs and families to provide the best financial assistance options given the patient's coverage to ensure timely access to DAYBUE.

除了這些付款人參與活動外，我們的 ACADIA Connect 支持服務中心以及我們的現場家庭訪問經理已經在為 HCP 和家庭提供有意義的支持，以根據患者的覆蓋範圍提供最佳的經濟援助選擇，以確保及時獲得DAYBUE。

And finally, following our approval, we hosted our first Rett community caregiver focused live webinar, sharing information about the product, how to enroll a loved one and obtain a prescription, the path to access and all of ACADIA's robust support services. The webinar was a big success with over 900 caregiver attendees, well above our internal targets. I'd like to reiterate that while we are only 3 weeks into the launch, we are highly encouraged with the response we've seen so far. We look forward to sharing more on our next quarterly call.

最後，在獲得批准後，我們舉辦了第一次以 Rett 社區護理人員為中心的現場網絡研討會，分享有關產品的信息、如何為親人註冊和獲得處方、獲取途徑以及 ACADIA 的所有強大支持服務。網絡研討會取得了巨大成功，有 900 多名護理人員參加，遠遠超過了我們的內部目標。我想重申，雖然我們距離發布僅 3 週，但我們對迄今為止看到的反響感到非常鼓舞。我們期待在下一個季度電話會議上分享更多信息。

Now let's discuss our NUPLAZID performance on Slide 12. In the first quarter of 2023, we grew demand bottles 2% compared to first quarter last year. Our performance was driven by an increase in new-to-brand prescription share and new patient starts across both the office space and long-term care channels. Beginning in fourth quarter and continuing now into the first, we have observed early indicators of growth in new patient starts for NUPLAZID.

現在讓我們在幻燈片 12 上討論我們的 NUPLAZID 性能。在 2023 年第一季度，與去年第一季度相比，我們對瓶子的需求增長了 2%。我們的業績是由新品牌處方份額的增加以及辦公空間和長期護理渠道的新患者開始推動的。從第四季度開始一直持續到第一季度，我們觀察到 NUPLAZID 新患者開始增長的早期指標。

As you may recall, new patient growth was negatively impacted during the pandemic as a direct result of the reduction in the overall patient population, fewer patients coming into the office or being admitted to a long-term care facility and a decrease in prescriptions of foundational PD treatments like carbidopa and levodopa. Thus, by maintaining steady volumes for NUPLAZID, we are actually continuing to grow share in an otherwise contracted PDP market.

您可能還記得，在大流行期間，新患者的增長受到了負面影響，這是由於總患者人數減少、就診或入住長期護理機構的患者減少以及基礎藥物處方減少的直接結果PD 治療，如卡比多巴和左旋多巴。因此，通過保持 NUPLAZID 的穩定銷量，我們實際上正在繼續擴大原本收縮的 PDP 市場的份額。

Furthermore, we are encouraged by the high level of engagement we are seeing from HCPs when presented with the real-world evidence data highlighting the potential differences in treatment with NUPLAZID compared to off-label antipsychotics. These datasets on mortality, safety and healthcare resource utilization create an important ongoing dialogue with physicians to further differentiate NUPLAZID as the first and only treatment option for their PDP patients.

此外，當我們看到真實世界的證據數據時，我們看到 HCP 的高度參與讓我們感到鼓舞，這些證據強調了 NUPLAZID 治療與適應症外抗精神病藥物治療的潛在差異。這些關於死亡率、安全性和醫療保健資源利用的數據集與醫生進行了重要的持續對話，以進一步區分 NUPLAZID 作為其 PDP 患者的第一個也是唯一的治療選擇。

We are pleased that our teams have grown market share and achieved early indicators of growth in new patient starts, all while continuing to optimize and reduce our NUPLAZID commercial expense base. With a focus on both top and bottom line, I'm proud to say that the NUPLAZID franchise has continued to grow profitability each year since turning cash flow positive in 2019.

我們很高興我們的團隊增加了市場份額並實現了新患者開始增長的早期指標，同時繼續優化和減少我們的 NUPLAZID 商業費用基礎。在關注收入和利潤的同時，我可以自豪地說，自 2019 年現金流轉為正數以來，NUPLAZID 特許經營權的盈利能力每年都在持續增長。

And with that, I'll turn it over to Doug Williamson to provide an update on our clinical programs.

有了這個，我會把它交給道格威廉姆森來提供我們臨床項目的最新情況。

Thank you, Brendan. Please turn to Slide 14. Firstly, to support the debut launch efforts. We continue to set up important opportunities for scientific exchange and sharing of medical information while also generating important new data for the Rett community. Our medical affairs team is off and running, including our medical science liaison team who have already delivered important scientific information and clinical education about DAYBUE to the Rett community. We continue to have a meaningful presence at the key medical congresses that are central to the Rett community, including the American Academy of Neurology Congress, or AAN, in April, and the upcoming International Rett Syndrome Foundation conference in June.

謝謝你，布倫丹。請翻到幻燈片14。首先，支持首發工作。我們繼續為科學交流和共享醫學信息創造重要機會，同時也為 Rett 社區生成重要的新數據。我們的醫療事務團隊正在運行，包括我們的醫學科學聯絡團隊，他們已經向 Rett 社區提供了有關 DAYBUE 的重要科學信息和臨床教育。我們繼續有意義地出席對 Rett 社區至關重要的重要醫學大會，包括 4 月份的美國神經病學學會大會 (AAN) 和即將於 6 月份召開的國際 Rett 綜合症基金會會議。

At AAN, we presented several posters which included important clinical presentations and data as well as surveys on disease education. In addition, we're excited for 2 very important clinical publications, which should be available in the coming months. One is the publication of the Phase III LAVENDER results and the other is a white paper on the best approaches to GI management associated with trofinetide. Finally, in the next month or so, we'll be initiating a large-scale prospective naturalistic study to learn more about how DAYBUE is best used in a real-world setting.

在 AAN，我們展示了幾張海報，其中包括重要的臨床介紹和數據以及疾病教育調查。此外，我們對 2 篇非常重要的臨床出版物感到興奮，它們應該會在未來幾個月內出版。一個是 III 期 LAVENDER 結果的發布，另一個是關於與 trofinetide 相關的 GI 管理最佳方法的白皮書。最後，在接下來的一個月左右，我們將啟動一項大規模的前瞻性自然研究，以了解更多有關如何在現實環境中最好地使用 DAYBUE 的信息。

Let's move on to our clinical programs, starting with pimavanserin as a potential treatment for the negative symptoms of schizophrenia on Slide 15. Persistent negative symptoms remain one of the largest unmet needs in schizophrenia. And as of today, there are still no approved treatments for these symptoms. The negative symptoms of schizophrenia are characterized by social withdrawal, lack of emotion or flat affect. Our adjunctive pimavanserin program is designed to treat the approximately 700,000 patients in the U.S. whose positive symptoms, the hallucinations, delusions and other psychosis are adequately controlled, but who still suffer from persistent and uncontrolled negative symptoms, inhibiting their ability to lead a normal productive life.

讓我們繼續我們的臨床計劃，從幻燈片 15 上的匹莫範色林開始，作為一種潛在的治療精神分裂症陰性症狀的藥物。持續的陰性症狀仍然是精神分裂症中最大的未滿足需求之一。直到今天，仍然沒有針對這些症狀的獲批治療方法。精神分裂症的陰性症狀的特徵是社交退縮、缺乏情緒或情緒低落。我們的輔助性匹莫範色林計劃旨在治療美國大約 700,000 名患者，他們的陽性症狀、幻覺、妄想和其他精神病得到充分控制，但仍遭受持續和不受控制的陰性症狀的困擾，抑制了他們過正常生產生活的能力.

Our second pivotal study, ADVANCE-2, is almost identical to our positive ADVANCE-1 study, but with 2 key differences: First, a clear learning from the ADVANCE-1 trial was that the optimal therapeutic dose for further evaluation of pimavanserin in negative symptoms of schizophrenia was the 34-milligram dose. And this is indeed the dose we're evaluating in ADVANCE-2; and second, it's well understood in our industry as well as by the FDA that placebo responses have become less reliable in U.S. schizophrenia trials over the past couple of decades. We also observed this in our U.S. sites of our ADVANCE-1 trial. And so now that we have the U.S. exposures we need, ADVANCE-2 is being conducted solely in sites outside the U.S. ADVANCE-2 is close to completing enrollment, which should occur around midyear with top line results in early 2024.

我們的第二項關鍵研究 ADVANCE-2 與我們的陽性 ADVANCE-1 研究幾乎相同，但有 2 個關鍵差異：首先，從 ADVANCE-1 試驗中清楚地了解到，匹莫範色林進一步評估陰性的最佳治療劑量精神分裂症的症狀是 34 毫克的劑量。這確實是我們在 ADVANCE-2 中評估的劑量；其次，我們的行業和 FDA 都清楚，在過去幾十年中，安慰劑反應在美國精神分裂症試驗中變得不那麼可靠了。我們還在我們的 ADVANCE-1 試驗的美國網站上觀察到這一點。因此，既然我們有了所需的美國風險，ADVANCE-2 將僅在美國以外的地點進行。ADVANCE-2 即將完成註冊，這應該在年中左右進行，並在 2024 年初取得一線結果。

Please turn to Slide 16. I'd like to provide an update on our next-generation 5-HT2A program and specifically the lead molecule ACP-204, which we're developing as a potential treatment for Alzheimer's disease psychosis. Similar to pimavanserin, ACP-204 works primarily by blocking 5-HT2A. We believe this mechanism is ideally suited for elderly populations, and with ACP-204, we are seeking to build on our learnings from pimavanserin. As Steve mentioned, we have completed our Phase I work for ACP-204. In these studies, in both healthy adults and elderly volunteers, we've focused on characterizing receptor occupancy and exposure and optimizing the doses we plan to evaluate in Phase II development. ACP-204 continues to demonstrate a very favorable safety and tolerability profile.

請轉到幻燈片 16。我想提供有關我們下一代 5-HT2A 計劃的最新信息，特別是先導分子 ACP-204，我們正在將其開發為阿爾茨海默病精神病的潛在治療方法。與匹莫範色林類似，ACP-204 主要通過阻斷 5-HT2A 發揮作用。我們相信這種機制非常適合老年人口，並且對於 ACP-204，我們正在尋求建立我們從匹莫萬色林中學到的東西。正如史蒂夫所說，我們已經完成了 ACP-204 的第一階段工作。在這些針對健康成人和老年志願者的研究中，我們專注於描述受體佔據和暴露的特徵，並優化我們計劃在 II 期開發中評估的劑量。 ACP-204 繼續表現出非常有利的安全性和耐受性。

In addition, we have confirmed that ACP-204 reaches steady state in less than half the time so roughly 5 days compared to around 12 days of pimavanserin, and this could potentially translate into a faster onset of action. Our work completed to date also appears to support our target product profile of minimizing the risk of QT prolongation. Our next steps are to meet with the FDA and discuss the future clinical development plan for ACP-204.

此外，我們已經確認 ACP-204 達到穩定狀態的時間不到一半，因此大約需要 5 天，而匹莫範色林需要大約 12 天，這可能會轉化為更快的起效。我們迄今為止完成的工作似乎也支持我們將 QT 延長風險降至最低的目標產品概況。我們接下來的步驟是與 FDA 會面並討論 ACP-204 的未來臨床開發計劃。

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

現在我會把它交給馬克進行財務更新。

Thank you, Doug. Let's review our quarterly performance on Slide 18. In the first quarter, we recorded $118.5 million in net sales, up 3% from the first quarter of last year. Our gross-to-net adjustment for the quarter was 29.3%. Year-over-year demand growth was up approximately 2% in the quarter driven by an increase in new patient starts across both channels. As Steve mentioned, selling volume declined approximately 2% year-over-year as in-channel inventory declined in the first quarter of 2023 compared to an increase in in-channel inventory in the first quarter of 2022.

謝謝你，道格。讓我們在幻燈片 18 上回顧一下我們的季度業績。第一季度，我們錄得 1.185 億美元的淨銷售額，比去年第一季度增長 3%。我們本季度的毛淨調整為 29.3%。在兩個渠道新患者開始增加的推動下，本季度需求同比增長約 2%。正如史蒂夫提到的那樣，與 2022 年第一季度渠道內庫存增加相比，2023 年第一季度渠道內庫存下降，銷量同比下降約 2%。

R&D expenses decreased to $69.1 million in Q1 2023 from $128.9 million in Q1 of 2022. The decrease is related to a $60 million upfront payment for our Stoke collaboration, which we recorded in Q1 2022. SG&A expenses increased slightly to $101.2 million in Q1 2023 from $96.7 million in Q1 2022. We continue to expect SG&A expenses to be essentially flat for 2023 versus 2022.

研發費用從 2022 年第一季度的 1.289 億美元減少到 2023 年第一季度的 6910 萬美元。減少與我們在 2022 年第一季度記錄的斯托克合作的 6000 萬美元預付款有關。SG&A 費用從 2023 年第一季度小幅增加到 1.012 億美元2022 年第一季度為 9670 萬美元。我們繼續預計 2023 年的 SG&A 費用與 2022 年基本持平。

This is a result of: one, the optimization and reduction of our NUPLAZID commercial expense base; and two, making the right investments to execute a successful launch of DAYBUE. We ended the quarter with a cash balance of $402.9 million compared to $416.8 million at the end of 2022. Our balance sheet remains strong, and we are confident in our ability to execute on our current business plan with our existing cash resources.

這是以下原因的結果：一是我們 NUPLAZID 商業費用基礎的優化和減少；第二，進行正確的投資以成功推出 DAYBUE。本季度末，我們的現金餘額為 4.029 億美元，而 2022 年底為 4.168 億美元。我們的資產負債表依然強勁，我們對利用現有現金資源執行當前業務計劃的能力充滿信心。

As you can see on Slide 19, we are reiterating all guidance measures for 2023, including net sales, gross-to-net and expense ranges.

正如您在幻燈片 19 中看到的那樣，我們重申了 2023 年的所有指導措施，包括淨銷售額、毛對淨額和費用範圍。

And now I'd like to turn the call over to Steve for closing remarks.

現在我想把電話轉給史蒂夫，讓他發表結束語。

Thanks, Mark. Please turn to Slide 21. I'd like to end today's prepared remarks focused on our execution across our 4 strategic priorities: first, DAYBUE was recently approved and launched only 3 weeks ago, we look forward to providing our first quarter of net sales for DAYBUE and appropriate performance metrics on the next earnings call; second, in our PDP commercial franchise, we look forward to continuing to driving share growth and profitability of NUPLAZID; third, we plan to complete enrollment in our Phase III ADVANCE-2 study for the negative symptoms of schizophrenia midyear with top line results expected in early 2024; and finally, we plan to meet soon with the FDA to discuss the clinical development plan for ACP-204.

謝謝，馬克。請轉到幻燈片 21。我想結束今天準備好的發言，重點是我們對 4 個戰略重點的執行：首先，DAYBUE 最近獲得批准並僅在 3 週前推出，我們期待提供第一季度的淨銷售額下一次財報電話會議上的 DAYBUE 和適當的績效指標；其次，在我們的 PDP 商業特許經營中，我們期待繼續推動 NUPLAZID 的份額增長和盈利能力；第三，我們計劃在年中完成針對精神分裂症陰性症狀的 III 期 ADVANCE-2 研究的招募，預計在 2024 年初獲得一線結果；最後，我們計劃很快與 FDA 會面，討論 ACP-204 的臨床開發計劃。

As always, I'd like to thank our employees for their accomplishments and their ongoing commitment and passion as we continue our mission to elevate life.

一如既往，我要感謝我們的員工在我們繼續履行提升生活使命的過程中所取得的成就以及他們持續的承諾和熱情。

(Operator Instructions) Our first call comes from Ritu Baral of TD Cowen.

（操作員說明）我們的第一個電話來自 TD Cowen 的 Ritu Baral。

I will just ask one. It's on your new payer discussions for DAYBUE, can you give us any more color on what those are focusing on? Specifically, are you seeing any unexpected prior-authorization requirements or, I guess, restrictions to a certain patient population, patient age, patient size, say, to the Phase III requirements? Or are they open to prescribing per label?

我只會問一個。這是關於 DAYBUE 的新付款人討論，你能給我們更多關於他們關注的內容的顏色嗎？具體來說，您是否看到任何意想不到的事先授權要求，或者，我猜，對特定患者群體、患者年齡、患者體型的限制，比如 III 期要求？或者他們是否願意按標籤開處方？

Thanks much for the question, Ritu. Brendan, do you want to take that?

非常感謝你的問題，Ritu。布倫丹，你想接受嗎？

Sure. Ritu, thanks for the question. And yes, we have been engaging payers ever since we got our final label. They've been very good and constructive encouraging discussions with payers. I think that they've largely demonstrated that they're following the process we would have expected for rare disease -- for rare disease products. We are working with them logistically to get early patients access through what would be considered a medical exception or a letter of medical necessity process, that is precisely what we expected and is going according to plan. We have not yet seen policy decisions. Those do happen -- can happen in a relatively short period of time, as you know. Some can take 30 to 60 days, more will take in the 60- to 90-day range and some can take up to 180 days. But as of now, we're really working in that interim period to get those first identified patients put on therapy while those policy decisions are being made.

當然。 Ritu，謝謝你的提問。是的，自從我們獲得最終標籤以來，我們一直在吸引付款人。他們與付款人進行了非常好的和建設性的鼓勵討論。我認為他們已經在很大程度上證明了他們正在遵循我們對罕見疾病——罕見疾病產品的預期過程。我們正在與他們進行後勤合作，讓早期患者通過被認為是醫療例外或醫療必要程序的信件進入，這正是我們所期望的，並且正在按計劃進行。我們還沒有看到政策決定。這些確實會發生——如您所知，可能會在相對較短的時間內發生。有些可能需要 30 到 60 天，更多的需要 60 到 90 天，有些可能需要長達 180 天。但截至目前，我們確實在那個過渡時期努力讓那些首先確定的患者在做出這些政策決定時接受治療。

And is there openness to reimburse, I guess, to the label versus clinical trial admission -- I'm sorry, inclusion criteria.

我猜，對於標籤與臨床試驗入場是否有報銷的開放性——對不起，納入標準。

Yes. Thanks again for the question. We are -- I guess, I'll say we're very pleased by, first of all, the breadth of the label that we've received -- we are encouraged by the breadth of enrollment forms that we've gotten from clinicians, from the youngest of patients to patients well over the age of 20, and we've also seen enrollment forms that have come from each of the different types of treatment settings from clinical trial sites all the way through to standalone neurology practices. And thus far, I think payers are working closely with us to gain -- to provide access to those early patients. We have not seen a meaningful restriction in these early days.

是的。再次感謝您的提問。我們 - 我想，我會說我們非常高興，首先，我們收到的標籤的廣度 - 我們對從臨床醫生那裡獲得的登記表的廣度感到鼓舞，從最年輕的患者到 20 歲以上的患者，我們還看到了來自臨床試驗地點一直到獨立神經病學實踐的各種不同類型治療環境的登記表。到目前為止，我認為付款人正在與我們密切合作以獲得 - 為那些早期患者提供訪問。在這些早期，我們還沒有看到有意義的限制。

Our next question comes from the line of Charles Duncan at Cantor Fitzgerald.

我們的下一個問題來自 Cantor Fitzgerald 的 Charles Duncan。

Hopefully, you can hear me...

希望你能聽到我...

Charles, you are very low, sir.

查爾斯，你太卑微了，先生。

Okay, I'll try to speak up. I had a question on the (inaudible) registry and for Rett. And I'm wondering what you think that will enable in terms of the production as well as the 2 (inaudible) here you mentioned particularly (inaudible) publication you see.

好吧，我會試著說出來。我有一個關於（聽不清）註冊表和 Rett 的問題。我想知道您認為這將在製作以及您在這里特別提到的 2（聽不清）出版物方面實現什麼（聽不清）。

Charles, I'm sorry. On our end, we can't hear you. We can hear you talking, but we can't make out your question.

查爾斯，對不起。在我們這邊，我們聽不到你的聲音。我們可以聽到你說話，但我們無法聽清你的問題。

Can you hear now?

你現在能聽到嗎？

Yes, much better. Yes, please continue. Go ahead, Charles.

是的，好多了。是的，請繼續。來吧，查爾斯。

Sorry about that. Sorry for taking in from the call. In terms of the Rett registry, how will that help you to drive adoption for DAYBUE as well with the 2 upcoming publications, has there been a pushback on the use of DAYBUE and management of diarrhea.

對於那個很抱歉。抱歉接聽電話。就 Rett 註冊表而言，這將如何幫助您推動 DAYBUE 以及即將發布的 2 個出版物的採用，是否存在對 DAYBUE 的使用和腹瀉管理的阻力。

Thanks much for the question, Charles. We've heard it this time. Brendan. I'll let you take that.

非常感謝查爾斯的提問。這次我們聽到了。布倫丹。我會讓你拿那個。

Sure, Charles. Thanks so much for the question. So in the real-world setting, we've been in the privileged position of being able to proactively communicate the benefits and tolerability profile of DAYBUE. We've been able to do that with clinicians and we've been able to do that with families as well.

當然，查爾斯。非常感謝你的問題。因此，在現實環境中，我們一直處於能夠主動傳達 DAYBUE 的益處和耐受性概況的特權地位。我們已經能夠對臨床醫生做到這一點，我們也能夠對家庭做到這一點。

So I would say with the appropriate GI management plan, it's been very well received. In fact, I would say that the feedback has been very positive, especially when we can reference the label itself that shows the clarity on discontinuing anti-constipation medicines as the FDA saw fit to put in the label.

所以我想說，通過適當的 GI 管理計劃，它得到了很好的接受。事實上，我想說反饋非常積極，尤其是當我們可以參考標籤本身時，它顯示了 FDA 認為適合放入標籤中的停用抗便秘藥物的清晰度。

And then I guess beyond that, we learned so much from the Phase III program that we're able to surround both clinicians and families with the type of support they need. We have our field-based family access managers, 18 of them that are paired specifically with the caregivers and patients and HCPs to make sure that we've set the right expectations for the best of treatment plans. And I don't know if Doug or Kathie wanted to speak about the real-world evidence piece -- real-world study.

然後我想除此之外，我們從 III 期計劃中學到了很多東西，我們能夠為臨床醫生和家庭提供他們需要的支持類型。我們有基於現場的家庭訪問管理器，其中 18 名專門與護理人員、患者和 HCP 配對，以確保我們對最佳治療計劃設定了正確的期望。我不知道 Doug 或 Kathie 是否想談談真實世界的證據——真實世界的研究。

Yes. Kathie, you want to comment on that.

是的。凱西，你想對此發表評論。

Yes, I'll take this, and Doug, you can chime in if I miss something. So Charles, as I mentioned on the call, as we roll out the launch. In parallel with that, we're offering patients the option and it's just an option if they want to. Caregivers can choose to enroll their Rett patient into a real-world evidence study. Just as Brendan mentioned that we learned a great deal through conducting the clinical trials. We are launching this study to learn additional information about how DAYBUE would be used in the real world both in terms of what efficacy it [will] affect over the long term and as well how clinicians and caregivers choose to manage the diarrhea in the real world, which I think is a lot easier to do outside the confines of the clinical trial where you're maybe on placebo, you also are confined to study budgets and things like that. So that's really the purpose of the study. It's sort of an optional add-on for patients who will go on commercial drug.

是的，我會接受這個，道格，如果我錯過了什麼，你可以插話。因此，正如我在電話中提到的那樣，查爾斯在我們推出發布會時。與此同時，我們為患者提供了選擇，如果他們願意，這只是一個選擇。護理人員可以選擇讓他們的 Rett 患者參加真實世界的證據研究。正如布倫丹所說，我們通過進行臨床試驗學到了很多東西。我們開展這項研究是為了了解有關 DAYBUE 如何在現實世界中使用的更多信息，包括它 [將] 長期影響的療效，以及臨床醫生和護理人員如何選擇在現實世界中管理腹瀉，我認為在你可能服用安慰劑的臨床試驗範圍之外做起來要容易得多，你也被限制在研究預算和類似的事情上。這就是這項研究的真正目的。對於將繼續使用商業藥物的患者來說，這是一種可選的附加組件。

Our next question comes from Tess Romero of JPMorgan.

我們的下一個問題來自摩根大通的 Tess Romero。

So beyond net revenues from sales of DAYBUE, what are the key metrics you will be providing the Street to gouge the health of the launch? And if you cannot provide those metrics to us today, qualitatively, how should we think about kind of what the key buckets or areas that you see as most valuable.

因此，除了 DAYBUE 銷售的淨收入之外，您將向華爾街提供哪些關鍵指標來衡量發布的健康狀況？如果你今天不能向我們提供這些指標，定性地，我們應該如何考慮你認為最有價值的關鍵領域或領域。

Yes. Thanks much for the question, Tess. Mark, do you want to take that?

是的。非常感謝你的問題，苔絲。馬克，你要拿那個嗎？

Yes. Thanks Tess. As we mentioned, we're only 3 weeks into launch. And at this stage, we just don't think it's constructive to share metrics today or even -- or just to sharing specifically what we will share on the next call. What we can commit to you and the investment community is that we not only will provide net revenue on our next call, but we will provide a reasonable set of metrics that we find will be meaningful at the time and going forward to give you insight in our progress on launch.

是的。謝謝苔絲。正如我們提到的，我們距離發布僅 3 週。在這個階段，我們只是認為今天甚至共享指標都沒有建設性——或者只是專門共享我們將在下一次電話會議上共享的內容。我們可以向您和投資界承諾的是，我們不僅會在下次電話會議上提供淨收入，而且還會提供一套合理的指標，我們認為這些指標在當時和未來都很有意義，可以讓您深入了解我們在發射方面的進展。

Our next question comes from Tazeen Ahmad at Bank of America.

我們的下一個問題來自美國銀行的 Tazeen Ahmad。

Can you hear me?

你能聽到我嗎？

Yes. We can, Tazeen.

是的。我們可以，塔贊。

Just wanted to ask you about ACP-204. As far as the Phase I data, when exactly should we be expecting to see that? And what level of data should we expect to see.

只是想問你關於 ACP-204 的問題。至於第一階段的數據，我們究竟應該在什麼時候看到？我們應該期望看到什麼級別的數據。

Great. Thanks much for the question. Doug, do you want to take that?

偉大的。非常感謝你的問題。道格，你想接受嗎？

Sure. So in Phase I, we explored and characterize the receptor occupancy and exposure and basically use that data internally to optimize the doses that we plan to evaluate in Phase II. So we don't plan to share details of the Phase I data, and it's really more important for those internal decisions and for the Phase II plan going beyond that. So we'll release more information once we've agreed on a development plan with the FDA and probably issue a press release after that meeting.

當然。因此，在第一階段，我們探索並描述了受體佔據和暴露的特徵，並基本上在內部使用該數據來優化我們計劃在第二階段評估的劑量。所以我們不打算分享第一階段數據的細節，這對於那些內部決策和超出此範圍的第二階段計劃來說真的更重要。因此，一旦我們與 FDA 就開發計劃達成一致，我們將發布更多信息，並可能在會後發布新聞稿。

Have you requested a meeting yet?

你要求會面了嗎？

We have.

我們有。

Our next question comes from Neena Bitritto-Garg from Citi.

我們的下一個問題來自花旗銀行的 Neena Bitritto-Garg。

So just on the trofinetide launch, you mentioned that about 90% of the patients that are expected to roll over, have initiated the process to get on commercial or paid drug. Can you just walk us through that extra 10%, why they haven't been initiated yet? And then what the overall timeline is now for expected completion of rollover of the open-label extension patients.

所以就在 trofinetide 發佈時，你提到大約 90% 預計會翻身的患者已經啟動了獲得商業或付費藥物的過程。你能告訴我們額外的 10%，為什麼他們還沒有開始？然後，現在預計完成開放標籤擴展患者的翻轉的總體時間表是什麼。

Brendan, do you want to take that?

布倫丹，你想接受嗎？

Sure. Neena, thanks so much for the question. And just to clarify, we have over -- I would say over 90% of eligible open-label extension patients have begun the process to become paid patients. So we're talking about a handful of additional patients that are also completing end-of-study visits with their trial investigators. At that point, the family is engaged with their insurance plans, of course, with ACADIA's support where needed and we'll help them with the completion of the adjudication process and converting to paid patients as soon as reasonably possible.

當然。尼娜，非常感謝你提出這個問題。澄清一下，我們已經結束了——我想說超過 90% 的符合條件的開放標籤擴展患者已經開始成為付費患者的過程。所以我們談論的是少數其他患者，他們也正在與他們的試驗調查員一起完成研究結束訪視。在這一點上，這個家庭正在參與他們的保險計劃，當然，在需要時 ACADIA 會提供支持，我們將幫助他們完成裁決過程並儘快轉為付費患者。

And for those handful of families where they're still in that process, I'm sure some of them just want to spend a little bit of time with their clinicians, take a look at the benefits that they're seeing and then decide how best to proceed. All in all, we will be pursuing support of 100% of those patients eligible for moving over. And we expect that, that process will take on average 2 to 3 months.

對於仍處於該過程中的少數家庭，我敢肯定他們中的一些人只是想花一點時間與他們的臨床醫生在一起，看看他們看到的好處，然後決定如何最好繼續。總而言之，我們將尋求 100% 有資格轉移的患者的支持。我們預計，該過程平均需要 2 到 3 個月。

Our next question comes from the line of Marc Goodman, SVB Securities.

我們的下一個問題來自 SVB 證券公司的 Marc Goodman。

This is Rudy Li for Mark. I have a question for NUPLAZID. Can you maybe talk about the current penetration of this product in the PDP population? And what are your current expectations for peak penetration?

這是 Mark 的 Rudy Li。我對 NUPLAZID 有疑問。您能否談談該產品目前在 PDP 人群中的滲透率？您目前對峰值滲透的期望是什麼？

Brendan, let you take the first part of that, and Mark for the second.

布倫丹，讓你來做第一部分，馬克做第二部分。

Sure. So thanks for the question. we reported in our prepared remarks that we have increased our share of new patient starts in the first quarter. That was in both the long-term care setting and in the community setting. And we also increased our new patient starts overall year-over-year in both of those populations. We don't provide guidance necessarily on where ultimately we believe penetration will be. But we do know that on the -- in the community-based setting, we're well over 20% and continuing to move that north. As you know, we started in long-term care after we started in the community setting. So that is growing and growing more rapidly, but is still kind of making up that space. And overall, we're over a 20% share for the entire NUPLAZID business across both channels.

當然。所以謝謝你的問題。我們在準備好的評論中報告說，我們在第一季度增加了新患者開始的份額。在長期護理環境和社區環境中都是如此。我們還在這兩個人群中增加了新患者的總體同比增長。我們不一定就我們認為滲透率最終會在哪裡提供指導。但我們確實知道，在基於社區的環境中，我們已經超過 20%，並繼續向北移動。如您所知，我們在社區環境中開始後才開始長期護理。所以它正在增長並且增長得更快，但仍然在某種程度上彌補了這個空間。總體而言，我們在兩個渠道的整個 NUPLAZID 業務中佔有超過 20% 的份額。

So Mark, I don't know if you want to add to that.

馬克，我不知道你是否想補充一點。

I think you covered both parts of the question.

我認為您涵蓋了問題的兩個部分。

Our next question comes from the line of Gregory Renza at RBC Capital Markets.

我們的下一個問題來自 RBC Capital Markets 的 Gregory Renza。

Steve and team, congrats on progress. Steve, maybe just a quick one for me as you've acknowledged the award of the priority review voucher on debut approval. Just wondering if you could update us on your latest thinking there as far as extracting the value and harnessing the value of the voucher either for you or for external parties. Clearly, I shared effort with Neuren, but also sponsors out there who are looking to accelerate their own programs before the FDA. Any color you have there would be great.

史蒂夫和團隊，祝賀進展。史蒂夫，也許對我來說只是一個快速的，因為你已經承認在首次批准時獲得了優先審查憑證的獎勵。只是想知道您是否可以向我們介紹您在為您或外部各方提取價值和利用代金券價值方面的最新想法。顯然，我與 Neuren 共同努力，但也有贊助商希望在 FDA 之前加速他們自己的項目。你有任何顏色都會很棒。

Yes. Thanks much for the question, Greg. I'll just take a little bit of a running start. I can remind you that we share the value of that with Neuren. But the decision in terms of how to utilize that voucher is entirely rests with us. And so we haven't determined yet whether we'll sell it or use it in one of our internal programs. If we use it, we have to pay Neuren their share based upon the value and there's an established market value for these things. And if we sell it, then we pay them their share of the proceeds from sell. So we haven't made a firm determination yet, but obviously, we're really happy to have it. These things are quite valuable and whether we ultimately use it for one of our programs or sell it will be a factor that will determine down the road.

是的。非常感謝你的問題，格雷格。我將開始一點點。我可以提醒您，我們與 Neuren 分享了這一點的價值。但如何使用該代金券的決定權完全取決於我們。因此，我們尚未確定是將其出售還是將其用於我們的內部程序之一。如果我們使用它，我們必鬚根據價值向 Neuren 支付他們的份額，並且這些東西有既定的市場價值。如果我們出售它，那麼我們會向他們支付他們在出售收益中的份額。所以我們還沒有下定決心，但顯然，我們真的很高興擁有它。這些東西非常有價值，我們最終是將它用於我們的一個項目還是出售它，這將是決定未來發展的一個因素。

Our next question comes from the line of Paul Matteis at Stifel.

我們的下一個問題來自 Stifel 的 Paul Matteis。

This is James on for Paul. Maybe just a quick one on ACP-204. I guess as you're thinking about subsequent clinical development plans, I guess, one, do you expect to be able to move right into pivotal studies? And two, are you thinking about running relapse prevention studies or in acute studies? I guess just any color on your clinical development plans would be great.

這是詹姆斯換保羅。也許只是關於 ACP-204 的快速介紹。我想當你在考慮後續的臨床開發計劃時，我想，第一，你希望能夠直接進入關鍵研究嗎？第二，您是在考慮進行複發預防研究還是急性研究？我猜你的臨床開發計劃中的任何顏色都會很棒。

Yes. Thanks much for the question. So as we stated earlier, based upon the profile of this drug, which is as we've said, closely enough related to pimavanserin to be in a space that we know what. We know the chemical space well, we know the biochemical space well. That puts us in a position where we have the opportunity to move aggressively with the program.

是的。非常感謝你的問題。因此，正如我們之前所說，根據這種藥物的概況，正如我們所說，它與匹莫範色林密切相關，處於我們所知道的空間。我們很了解化學空間，我們也很了解生化空間。這使我們有機會積極推進該計劃。

So as Doug mentioned in his prepared remarks, we're not quite ready to describe exactly what the phase II to and beyond program looks like. I'll simply say that once we've met with FDA, we'll be in a position to go into that in much greater detail. And as Doug mentioned on the call, at this point, now having completed Phase I, the target product profile that we -- that we set as our goal in this continues to look extremely attractive. The drug is in Phase I, was very well behaved, very well tolerated. No safety issues clearly appears to get to a steady state and therefore, potentially a faster onset of action than pimavanserin.

因此，正如道格在他準備好的發言中提到的那樣，我們還沒有完全準備好準確描述第二階段及以後的計劃是什麼樣的。我只想說，一旦我們與 FDA 會面，我們將能夠更詳細地討論這個問題。正如道格在電話中提到的那樣，在這一點上，現在已經完成了第一階段，我們設定為目標的目標產品概況繼續看起來極具吸引力。該藥物處於 I 期，表現非常好，耐受性非常好。沒有明顯的安全問題出現達到穩定狀態，因此可能比匹莫範色林起效更快。

We've seen no indications of QT issues at this point. And this profile that we see with these 5-HT2A blockers appears to be carrying forward with 204 in providing a lot of the benefits that we see with ADVANCE or plus some based upon the design features that we set as our goal. So we're eager to get to the point we can talk more about that, but the next step is to meet with the FDA and then we'll go into greater detail.

此時我們還沒有看到 QT 問題的跡象。我們在這些 5-HT2A 阻斷劑中看到的這種配置文件似乎在 204 中得到發揚光大，提供了我們在 ADVANCE 中看到的許多好處，或者加上一些基於我們設定為目標的設計特徵。所以我們急切地希望能夠就此進行更多討論，但下一步是與 FDA 會面，然後我們將討論更多細節。

Our next question comes from Jason Butler at JMP.

我們的下一個問題來自 JMP 的 Jason Butler。

Just one on the PDP market dynamics. You've said now for a couple of quarters that you're seeing early signs of growth in new patient starts. Can you maybe just give us a little bit more context there of where you think in the office space setting, we stand today versus pre-pandemic or where you think a future normalized level would stand?

只是關於 PDP 市場動態的一個。幾個季度以來，您一直在說您看到了新患者開始增長的早期跡象。你能不能給我們更多的背景信息，比如你在辦公空間環境中的想法，我們今天的立場與大流行前的立場，或者你認為未來的正常水平會處於什麼位置？

Yes. Thanks much for the question, Jason. Brendan, do you want to take that?

是的。傑森，非常感謝你提出這個問題。布倫丹，你想接受嗎？

Sure. Thanks for the question. And yes, if we're -- if we look at it in context to, I'll say, mid-pandemic, I think that there is a market dynamic in the community setting that is relatively consistent at this point. We still see fewer in-office, in-person patient visits and we see a flat PD market in terms of use of carbidopa-levodopa. So essentially 0% growth year-over-year.

當然。謝謝你的問題。是的，如果我們——如果我們在大流行中期的背景下看待它，我認為社區環境中存在一種市場動態，此時相對一致。我們仍然看到更少的辦公室、面對面的患者就診，我們看到卡比多巴-左旋多巴的 PD 市場持平。因此，同比增長基本上為 0%。

As we've stated on previous calls, we're focused on the real world evidence data that exists to help us differentiate NUPLAZID from other atypical antipsychotics in terms of outcomes. Those 3 data sets have been important additions to, I think, the whole clinical discussion of this category. And I think they've been very well received by our audiences, both in the community and in the long-term care setting.

正如我們在之前的電話會議上所說，我們專注於現實世界的證據數據，這些數據可以幫助我們在結果方面將 NUPLAZID 與其他非典型抗精神病藥區分開來。我認為，這 3 個數據集是對這一類別的整個臨床討論的重要補充。而且我認為他們在社區和長期護理環境中都受到了我們觀眾的歡迎。

So for us, from a midpoint of the pandemic where new patient starts had slowed down, I think, along with the market. We're encouraged to see that we're able to increase new patient starts and increase share in what is otherwise contracted PD market. That, for me, is the best way to describe this, encouraging results on the NUPLAZID and for new starts in a market that has been a little bit sluggish in the early part of '23.

因此，對我們來說，從大流行的中點開始，我認為新患者開始放緩的速度與市場一起放緩。我們很高興看到我們能夠增加新患者的開始，並增加在其他收縮的 PD 市場中的份額。對我來說，這是描述這一點的最佳方式，令人鼓舞的 NUPLAZID 成果以及在 23 世紀初期有點低迷的市場中的新開端。

Our next question comes from Jason Hung (sic) [Jeff Hung] of Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Jason Hung（原文如此）[Jeff Hung]。

This is Jeff. Can you talk about your updated thoughts on business development? How important is it to you to be cash flow positive versus further expanding your mid- to late-stage pipeline, say, with M&A?

這是傑夫。能否談談您對業務發展的最新思考？現金流為正與通過併購進一步擴大中後期管道對您來說有多重要？

Yes. Thanks much for the question. So as we've stated previously, business development continues to be a very important part of our business. We have now an established franchise both in neurology and psychiatry, established franchises in rare disease and broad applications, and we have an opportunity to leverage those capabilities, and we'll continue to do that.

是的。非常感謝你的問題。因此，正如我們之前所說，業務發展仍然是我們業務中非常重要的一部分。我們現在在神經病學和精神病學領域擁有既定的專營權，在罕見疾病和廣泛應用方面建立了專營權，我們有機會利用這些能力，我們將繼續這樣做。

The question in terms of prioritization of profitability versus continuing to build the company for the future is -- the answer is we're going to do both. We're going to continue executing on business development, particularly in an environment that is much more attractive today than it has been in any time in recent history. But we will continue to also be very judicious about the investments we're making. And as Mark mentioned in his prepared remarks and as you've heard us say before, with the PDP franchise as an example, that franchise became profitable and began throwing off cash in 2019. It's become more profitable every year since then, and we'll continue to have that as a top priority. So as we move forward, you'll continue to see us exercising discretion as well as investment opportunities on both fronts.

關於優先考慮盈利能力與繼續為未來建設公司的問題是——答案是我們將兩者兼顧。我們將繼續執行業務發展，特別是在當今比近代歷史上任何時候都更具吸引力的環境中。但我們將繼續對我們正在進行的投資保持非常審慎的態度。正如馬克在他準備好的發言中提到的那樣，正如你之前聽到我們所說的那樣，以 PDP 特許經營權為例，該特許經營權在 2019 年開始盈利並開始拋出現金。從那時起，它每年都變得更有利可圖，我們'我們將繼續把它作為首要任務。因此，隨著我們向前邁進，您將繼續看到我們在這兩個方面行使自由裁量權和投資機會。

Our next question comes from Salveen Richter at Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

This is Matt on for Salveen. We were just interested, is there a specific patient group where docs are more keen on using DAYBUE. Some of our checks with doctors suggested a preference to use the drug in stable early-stage patients versus late-stage ones. So I just wanted to see if that was in line with what you're seeing. And then could you share what you view as the most important takeaways from the [AAN presentations].

這是 Salveen 的 Matt。我們只是感興趣，是否有一個特定的患者群體，醫生更熱衷於使用 DAYBUE。我們與醫生進行的一些檢查表明，與晚期患者相比，我們更願意將這種藥物用於穩定的早期患者。所以我只是想看看這是否與您所看到的一致。然後你能分享一下你認為從 [AAN 演講] 中得到的最重要的收穫嗎？

Yes. I'm sorry, we didn't hear the second part of the question.

是的。對不起，我們沒有聽到問題的第二部分。

Just what you view as the most important takeaways from your AAN presentation.

您認為 AAN 演示文稿中最重要的內容。

Got it. Okay. Brendan, do you want to take this question?

知道了。好的。布倫丹，你想回答這個問題嗎？

Sure. Matt, thanks for the question. Obviously, we're 3 weeks in and have been watching with keen interest to see what patient populations our audience would look to address. I'd go back to the prepared remarks, however, to show you that with a broad label, we've been very encouraged by the breadth of enrollment forms that we're seeing. And it's indicative, I think, of what we saw in the LAVENDER study, which demonstrated that regardless of age or severity of disease across the 8 domains of the RSBQ, we've seen improvements, and that means that both clinicians and caregivers are going to look at their individual patients and say, I think there's an opportunity to help improve this individual patient's situation.

當然。馬特，謝謝你的提問。顯然，我們已經進行了 3 週，並且一直懷著濃厚的興趣觀察我們的觀眾希望解決哪些患者群體。然而，我會回到準備好的評論中，向您展示，有了廣泛的標籤，我們對我們所看到的廣泛的登記表感到非常鼓舞。我認為，這表明我們在 LAVENDER 研究中看到的情況，該研究表明，無論 RSBQ 的 8 個領域的年齡或疾病嚴重程度如何，我們都看到了改善，這意味著臨床醫生和護理人員都在看看他們的個體患者並說，我認為有機會幫助改善這個個體患者的情況。

So as I've said, I wish I could point you to a particular patient type, but we're very encouraged that there's a broad range of patients that are being considered for DAYBUE both in terms of age as young as 2 and well above 20. We've seen male and female patients. We've seen patients that are across the disease severity spectrum. Some clinicians looking to start with patients that are maybe on the thicker end of the scale and others looking to intervene as early as they can in a younger patient population. So it's still very, very early days to see. But in terms of the feedback that we've gotten from clinicians, we're not seeing a particular interest in a subset, for example, of Rett patients.

所以正如我所說，我希望我能指出一個特定的患者類型，但我們非常鼓舞的是，有廣泛的患者正在考慮使用 DAYBUE，無論是 2 歲還是 2 歲以上20. 我們見過男性和女性患者。我們見過各種疾病嚴重程度的患者。一些臨床醫生希望從可能處於較厚一端的患者開始，而另一些臨床醫生則希望儘早干預較年輕的患者群體。所以現在還為時尚早。但就我們從臨床醫生那裡得到的反饋而言，我們並沒有看到對 Rett 患者的一個子集特別感興趣。

And Kathie, can you talk about AAN?

凱西，你能談談 AAN 嗎？

I can talk about AAN. So on the clinical side, we had 2 main presentations from our clinical trial data. One was additional data from our LAVENDER Phase III study on the benefits observed with the view on communication, especially nonverbal communication end point. As we previously talked about, communication is one of the key aspects of the disease that caregivers and parents really would like to see improvement. Most patients with Rett syndrome lose the ability to speak and cannot even communicate, not verbally with things like eye gaze or pointing out what they want.

我可以談談AAN。因此，在臨床方面，我們的臨床試驗數據有 2 個主要介紹。一個是來自我們的 LAVENDER III 期研究的額外數據，該研究關於從溝通的角度觀察到的好處，尤其是非語言溝通終點。正如我們之前談到的，溝通是看護者和父母真正希望看到改善的疾病的關鍵方面之一。大多數 Rett 綜合症患者失去了說話的能力，甚至無法進行交流，不能用眼神或指出他們想要的東西來進行口頭交流。

So in the Phase III LAVENDER trial, we included a key secondary endpoint to assess nonverbal communication, the CSBS and then we actually had an additional functional task asking them to indicate preferences as a surrogate for nonverbal communication. And then we saw a benefit with DAYBUE for both of these nonverbal communication endpoints compared to placebo.

因此，在 III 期 LAVENDER 試驗中，我們包括了一個關鍵的次要終點來評估非語言交流，即 CSBS，然後我們實際上還有一項額外的功能性任務，要求他們表明偏好作為非語言交流的替代品。然後我們看到與安慰劑相比，DAYBUE 對這兩個非語言交流端點都有好處。

So the presentation at AAN focused on that, we actually will have a publication we're putting together on that data. The second clinical presentation at AAN was in the DAFFODIL study, which is the younger girls aged 2 to 4 who've been on open-label DAYBUE for all for over a year now. And with that, we saw a very consistent safety tolerability profile compared to the Phase III data, no new safety or tolerability outcomes in that study. And we've even had a lower discontinuation rate due to diarrhea with only 1 patient discontinuing over the year.

因此，AAN 的演示集中於此，我們實際上將發布一份關於該數據的出版物。 AAN 的第二個臨床表現是在 DAFFODIL 研究中，該研究是 2 至 4 歲的年輕女孩，她們已經接受開放標籤 DAYBUE 一年多了。因此，與 III 期數據相比，我們看到了非常一致的安全耐受性概況，該研究中沒有新的安全性或耐受性結果。我們甚至因腹瀉而停藥的比例更低，全年只有 1 名患者停藥。

And then in addition, we included some initial exploratory endpoints looking at efficacy. The younger girls are harder to study efficacy because they are in a period of regression is very variable, where they lose ability, but there's a lot of individual variability in that what we are seeing steady outcomes as far as efficacy and some hints of improvement on DAYBUE.

此外，我們還包括了一些觀察療效的初步探索性終點。年輕女孩更難研究功效，因為她們處於退化期，她們會失去能力，但個體差異很大DAYBUE。

In addition to those two, we did have a couple of other presentations on health economics outcomes just showing the burden of disease that Rett syndrome causes in these patients and these families.

除了這兩個之外，我們還有其他一些關於健康經濟學結果的演講，只是展示了 Rett 綜合徵在這些患者和這些家庭中造成的疾病負擔。

Our next question comes from Yatin Suneja of Guggenheim.

我們的下一個問題來自古根海姆的 Yatin Suneja。

Two real quick ones. With regard to the DAYBUE, could you comment on how should we model duration of therapy? That's one. The second one on NUPLAZID. Second quarter generally is a stronger quarter. Past -- should we look at the past or the last couple of years and predict how the second quarter is going to look like? Or are there any key changes this year versus, let's say, last year?

兩個真正快速的。關於 DAYBUE，您能否評論一下我們應該如何模擬治療持續時間？那是一個。 NUPLAZID 上的第二個。第二季度通常是一個更強勁的季度。過去——我們應該回顧過去或過去幾年並預測第二季度的情況嗎？或者說，與去年相比，今年有什麼重大變化嗎？

Yes. Thanks much for the question. Brendan, do you want to take the first question and Mark, the second one.

是的。非常感謝你的問題。布倫丹，你想回答第一個問題，馬克回答第二個問題嗎？

Sure, thank you so much for your question. We're not really providing internal estimates on this concept of duration and persistency because there is, of course, going to be a range, but I'll give as much color as I can as to what we're thinking. First and foremost, as we said, we learned an awful lot from the Phase III study, LAVENDER. And as a function of that, we've known what to expect.

當然，非常感謝你的問題。我們並沒有真正提供關於持續時間和持久性這個概念的內部估計，因為當然會有一個範圍，但我會盡可能多地說明我們的想法。首先，正如我們所說，我們從 III 期研究 LAVENDER 中學到了很多東西。因此，我們知道會發生什麼。

You've heard in the last couple of calls where we've talked about all of the support systems we've put in place. And obviously, we want nothing more than for patients and families to see the long-term benefit that DAYBUE stands to offer from the work that's been done in LAVENDER, the additional work that's been done in the open-label extensions and hopefully beyond. So we're -- there are a couple of things that lead us to believe that we can be supportive in the real-world setting to get to those outcomes.

在過去的幾個電話中，您已經聽到我們討論了我們已經建立的所有支持系統。顯然，我們只想讓患者和家屬看到 DAYBUE 從 LAVENDER 中所做的工作中提供的長期利益，以及在開放標籤擴展中所做的額外工作，並希望超越。所以我們 - 有幾件事讓我們相信我們可以在現實環境中提供支持以實現這些結果。

But first, we were obviously very pleased with the label. The label allows us to speak to discontinuation of anti-constipation medications from the outset. That's very important. It sets up the right treatment expectation with both clinician and family.

但首先，我們顯然對這個標籤非常滿意。該標籤使我們能夠從一開始就停止使用抗便秘藥物。這非常重要。它與臨床醫生和家庭建立了正確的治療期望。

The second is that we have proactively been able to work with the HCP audience and families to discuss educational efforts on GI management. Both of those set those audiences up for the appropriate expectations as they move into treatment with DAYBUE. And then we support them in the field with the family access manager team, which I said, these folks are paired specifically with each patient and family so that we can be well positioned to hold their hands from the outset on the beginning of this treatment journey, both for the patients and caregivers.

第二，我們已經能夠主動與 HCP 觀眾和家庭合作，討論 GI 管理方面的教育工作。當這些觀眾開始接受 DAYBUE 治療時，這兩者都為他們設定了適當的期望。然後我們通過家庭訪問管理團隊在現場支持他們，我說過，這些人專門與每個患者和家庭配對，這樣我們就可以在治療旅程的開始從一開始就握住他們的手，無論是對於患者還是護理人員。

So for us, we believe that sets up the best of all patient experiences, again, looking to get to the long-term benefit for DAYBUE. And while we're in the very early days, the feedback we've gotten both from clinicians and families has been very positive about setting the appropriate treatment course, but more importantly, having the support necessary for them to begin and stay on that journey.

因此，對我們來說，我們相信這會再次為所有患者帶來最好的體驗，希望為 DAYBUE 帶來長期利益。雖然我們還處於起步階段，但我們從臨床醫生和家屬那裡得到的反饋對設置適當的治療方案非常積極，但更重要的是，為他們提供必要的支持，讓他們開始並堅持這一旅程.

Thanks much Brendan. Mark, do you want to take NUPLAZID seasonality?

非常感謝布倫丹。馬克，您想服用 NUPLAZID 季節性嗎？

Yes. No, thanks for the question. As you know, we don't provide quarterly guidance, but let me just share some additional color, which I think will be helpful. I think as we discussed on this quarter, there tends to be some seasonality as patients -- for patients as they go through the Medicare reauthorization process that happens for all patients in Q1. It's just that process just happens for new patients as we move on later in the year.

是的。不，謝謝你的提問。如您所知，我們不提供季度指導，但讓我分享一些額外的顏色，我認為這會有所幫助。我認為正如我們在本季度討論的那樣，作為患者往往存在一些季節性——對於患者來說，因為他們經歷了第一季度對所有患者發生的醫療保險重新授權過程。隨著我們在今年晚些時候繼續前進，這個過程只會發生在新患者身上。

So you'll have that dynamic tends to be more positive going forward Q2 through Q4. We also have the higher gross-to-net in the first quarter primarily due to the reauthorization process and our obligation for that for all patients. That will be lower again in the second quarter and third quarter, a little higher in the fourth quarter, typical with kind of the seasonality that you've seen in past years. I'd just remind you, this year, we do have the impact of the Inflation Reduction Act.

因此，從第二季度到第四季度，您的動態往往會更加積極。我們在第一季度的淨利潤率也較高，這主要是由於重新授權程序以及我們對所有患者的義務。第二季度和第三季度會再次降低，第四季度會略高，典型的是你在過去幾年看到的那種季節性。我只想提醒你，今年我們確實受到了《通貨膨脹減少法案》的影響。

So our gross-to-net will be higher year-over-year on a quarterly basis and consistent just with our overall annual guidance. And then as far as just seasonality between quarters, obviously, we'll report results as we go through. Our revenues are obviously impacted by volumes, patient volumes, so how the results of patient volumes throughout the rest of the year will impact our sales on a quarterly basis.

因此，我們的毛淨收入將按季度同比增長，並且與我們的總體年度指導一致。然後就季度之間的季節性而言，很明顯，我們將報告結果。我們的收入顯然受到數量、患者數量的影響，因此今年剩餘時間的患者數量結果將如何影響我們的季度銷售額。

Thank you, everyone. This is all the time we have for today. I'll now turn it over to Steve Davis, CEO, for closing remarks.

謝謝大家。這是我們今天的全部時間。現在，我將把它交給首席執行官史蒂夫·戴維斯 (Steve Davis) 作結束語。

Great. Thank you, operator. Thanks again, everyone, for joining us today. We look forward to updating you on our progress next quarter.

偉大的。謝謝你，運營商。再次感謝大家今天加入我們。我們期待在下個季度向您通報我們的進展情況。

Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect. Good day.

感謝您參加今天的電話會議。介紹到此結束。您現在可以斷開連接。再會。