Alkermes Plc (ALKS) 2024 Q4 法說會逐字稿

Greetings, and welcome to the Alkermes fourth quarter 2024 financial results conference call. My name is Melissa, and I will be your operator for today's call.

大家好，歡迎參加 Alkermes 2024 年第四季財務業績電話會議。我叫梅麗莎，今天我將擔任您的電話接線生。

(Operator Instructions) Please note this conference call is being recorded. I will now turn the call over to Sandra Coombs, Senior Vice President of Investor Relations and Corporate Affairs. Thank you. You may begin.

（操作員指示）請注意，本次電話會議正在錄音。現在我將把電話轉給投資者關係和公司事務高級副總裁桑德拉庫姆斯 (Sandra Coombs)。謝謝。你可以開始了。

Thank you. Good morning. Welcome to the Alkermes PLC conference call to discuss our financial results and business update for the quarter and year ended December 31, 2024. With me today are Richard Pops, our CEO; Blair Jackson, our Chief Operating Officer; and Todd Nichols, our Chief Commercial Officer.

謝謝。早安.歡迎參加 Alkermes PLC 電話會議，討論我們截至 2024 年 12 月 31 日的季度和年度的財務業績和業務更新。今天和我一起的是我們的執行長理查德·波普斯 (Richard Pops)；布萊爾·傑克遜 (Blair Jackson)，我們的首席營運長；以及我們的首席商務官托德·尼科爾斯（Todd Nichols）。

A slide presentation along with our press release, related financial tables, and reconciliations of the GAAP to non-GAAP financial measures that we'll discuss today are available on the Investors section of alkermes.com. We believe the non-GAAP financial results in conjunction with the results are useful in understanding the ongoing economics of our business.

我們今天將要討論的幻燈片演示以及新聞稿、相關財務表以及 GAAP 與非 GAAP 財務指標的對帳可在 alkermes.com 的投資者部分找到。我們相信，非公認會計準則財務結果與績效相結合有助於了解我們業務的持續經濟狀況。

Our discussions during this conference call will include forward-looking statements. Actual results could differ materially from these forward-looking statements. Please see slide 2 of the accompanying presentation, our press release issued this morning and our most recent annual report filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements.

我們在本次電話會議中的討論將包括前瞻性陳述。實際結果可能與這些前瞻性陳述有重大差異。請參閱隨附簡報的第 2 張投影片、我們今天早上發布的新聞稿以及我們向美國證券交易委員會提交的最新年度報告，以了解可能導致我們的實際結果與前瞻性陳述中表達或暗示的結果存在重大差異的重要風險因素。

We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results or developments. After our prepared remarks, we'll open the call for Q&A.

對於因新資訊或未來結果或發展而更新或修改本次電話會議或隨附簡報中提供的信息，我們不承擔任何義務。在我們準備好發言後，我們將開始問答環節。

And now I'll turn the call over to Richard for some opening remarks.

現在我將把電話轉給理查德，請他致一些開場白。

Thank you, Sandy. Good morning, everyone. So 2024 was a year defined by commercial execution, efficiency and profitability, and pipeline progress. During the year, key achievements across each of these initiatives demonstrated the realization of our goal of becoming a pure-play, highly profitable, fully integrated neuroscience biopharmaceutical company. This morning, we'll review our strong 2024 financial performance will discuss our financial expectations for 2025 and provide our view of the key value creation opportunities for Alkermes in this year ahead. Blair and Todd are going to give you the details, but here's my view in the aggregate.

謝謝你，桑迪。大家早安。因此，2024 年將是由商業執行、效率和盈利能力以及管道進展決定的一年。這一年，各項措施所取得的關鍵成就表明，我們已實現成為一家純粹、高利潤、完全一體化的神經科學生物製藥公司的目標。今天上午，我們將回顧我們強勁的 2024 年財務業績，討論我們對 2025 年的財務預期，並提供我們對未來一年 Alkermes 的關鍵價值創造機會的看法。布萊爾和托德將會向你提供詳細情況，但我的整體看法如下。

2024 was a banner financial year for the company. We exceeded $1.5 billion in revenue, primarily driven by our proprietary commercial portfolio of medicines discovered, developed and commercialized biographies. We manage the business to drive robust profitability and met our EBITDA goal. This yielded more than $450 million of EBITDA for continuing operations while investing in the pipeline programs that we believe will drive the future growth of the company. We use the profits we generate to strengthen the balance sheet. We repurchased approximately 8 million shares, retired all of our debt, and ended the year with $825 million of cash on the balance sheet.

2024年是該公司財政表現輝煌的一年。我們的收入超過 15 億美元，這主要得益於我們發現、開發和商業化的專有商業藥物組合。我們管理業務以實現強勁的盈利能力並實現我們的 EBITDA 目標。這為持續經營帶來了超過 4.5 億美元的 EBITDA，同時投資了我們認為將推動公司未來成長的管道項目。我們利用所創造的利潤來強化資產負債表。我們回購了約 800 萬股股票，償還了所有債務，年底時資產負債表上有 8.25 億美元現金。

We take the same financial ethos into 2025, and we'll continue to manage the business with a focus on profitability. As we previously outlined on our last earnings call, we expect to generate over $200 million of EBITDA in 2025 while advancing the [ARTISTRY] program as aggressively as we can. The financial expectations for 2025 that Blair will outline next, reflect the line of sight we have into the current dynamics with customers and payers in the competitive markets where we operate.

我們將把同樣的財務精神帶入 2025 年，並​​繼續以盈利能力為重點管理業務。正如我們在上次財報電話會議上概述的那樣，我們預計在 2025 年創造超過 2 億美元的 EBITDA，同時盡可能積極地推進 [ARTISTRY] 計劃。布萊爾接下來將概述的 2025 年財務預期反映了我們對所處競爭市場中客戶和付款人的當前動態的觀察。

For our mature products, VIVITROL and ARISTADA, we expect flat to modest growth and for our most recently launched product, LYBALVI, continued growth and uptake in those markets. We'll take you through the specifics, particularly for Q1, so we can all start the year in alignment. As we prepare for key ALKS 2680 Phase II data rate later this year, we're focused on delivering solid and predictable financial performance.

對於我們成熟的產品 VIVITROL 和 ARISTADA，我們預計將保持平穩至適度增長，而對於我們最近推出的產品 LYBALVI，其在這些市場將繼續增長並受到歡迎。我們將向您介紹具體情況，特別是第一季的具體情況，以便我們都能以一致的方式開始新的一年。在我們為今年稍後的關鍵 ALKS 2680 第二階段數據率做準備時，我們專注於提供穩健且可預測的財務表現。

All of that leads to what we think is the principal value driver for the company in 2025, key data readouts for our lead development candidate, ALKS 2680, which is currently enrolling two well-powered, randomized, placebo-controlled Phase II studies in patients with narcolepsy.

所有這些都導致​​了我們認為的 2025 年公司的主要價值驅動力，即我們的主要開發候選藥物 ALKS 2680 的關鍵數據讀數，該藥物目前正在針對嗜睡症患者招募兩項具有良好效果的、隨機的、安慰劑對照的 II 期研究。

With planned cumulative enrollment of 160 patients and expected completion in the second half of this year, we designed these studies to provide robust data sets, it will highlight the key characteristics of this campaign. And along with that, the commercial opportunity and competitive positioning associated with it. I'll provide some additional insights into the 2680 developed program later in the call. But for now, the point is that ALKS 2680 is on the threshold of revealing its medical and its commercial potential.

我們計劃累計招募 160 名患者，預計今年下半年完成，我們設計這些研究是為了提供強大的數據集，它將突出這次活動的主要特徵。除此之外，還有與之相關的商業機會和競爭定位。我稍後會在通話中提供一些有關 2680 開發程序的額外見解。但目前的重點是 ALKS 2680 即將展現其醫療和商業潛力。

We are a leader in the development of new medicines based on orexin biology, which is one of the most exciting potential new therapeutic categories within neuroscience, and it represents a transformational opportunities for Alkermes in the years ahead. We've been laying the groundwork for 2025 for several years and we're well positioned heading into this eventful year. So with that, as an overall introduction, I'm going to turn it over to Blair.

我們是基於食慾素生物學的新藥開發領域的領導者，這是神經科學領域中最令人興奮的潛在新治療類別之一，它代表了 Alkermes 未來幾年的轉型機會。我們已經為 2025 年做好了多年的基礎準備，並且已經為迎接這個多事之秋做好了充分的準備。因此，作為一個總體介紹，我將把它交給布萊爾。

Thank you, Rich. 2024 was Alkerme's strongest year of financial and operational performance to date. Financially, we generated more than $1 billion in revenue from our proprietary commercial product portfolio, delivered EBITDA from continuing operations of approximately $452 million, repurchased $200 million of the company's shares, retired $290 million of debt, and ended the year debt-free with approximately $825 million of cash on the balance sheet.

謝謝你，里奇。 2024 年是 Alkerme 迄今為止財務和營運業績最強勁的一年。在財務方面，我們從專有的商業產品組合中創造了超過 10 億美元的收入，來自持續經營的 EBITDA 達到約 4.52 億美元，回購了 2 億美元的公司股份，償還了 2.9 億美元的債務，並且年底沒有債務，資產負債表上約有 8.25 億美元的現金。

Operationally, we completed the sale of our manufacturing business in Ireland, which streamlined our manufacturing footprint and positioned the company to expand gross margins going forward. We also made significant progress advancing our neuroscience development pipeline and are looking forward to important Phase II data read outs this year for our lead candidate, ALKS 2680 in narcolepsy.

在營運方面，我們完成了在愛爾蘭製造業務的出售，這簡化了我們的製造足跡，並使公司未來能夠擴大毛利率。我們也在推進神經科學開發管道方面取得了重大進展，並期待今年讀取我們用於治療嗜睡症的主要候選藥物 ALKS 2680 的重要 II 期數據。

In 2024, we generated total revenues of worth $1.5 billion, driven primarily by our proprietary product, which grew 18% year-over-year and generated more than $1 billion in net sales. For the year, we recorded VIVITROL net sales of $457.3 million, reflecting 14% growth year-over-year. Net sales of the ARISTADA product family increased 6% year-over-year to $346.2 million in 2024. And revolving net sales increased 46% year-over-year to $280 million.

2024 年，我們的總營收達到 15 億美元，主要得益於我們的專有產品，該產品年增 18%，淨銷售額超過 10 億美元。今年，VIVITROL 的淨銷售額為 4.573 億美元，年增 14%。2024年，Aristada 產品系列的淨銷售額年增 6% 至 3.462 億美元。循環淨銷售額年增 46% 至 2.8 億美元。

Across the proprietary commercial portfolio, due to the timing of shipments ahead of the holidays, the fourth quarter included an extra ordering cycle to cover the first week of the year. Inventory normalized to preholiday levels in early January, so you can think about this as pulling in one week of orders from Q1 into Q4. These dynamics resulted in year-end wholesaler inventory build of approximately $20 million and primarily impacted VIVITROL and ARISTADA.

在專有商業產品組合中，由於假期前的發貨時間，第四季度增加了一個額外的訂購週期以涵蓋今年的第一周。庫存在 1 月初就恢復到了節前的水平，因此你可以將其視為將第一季一周的訂單拉到了第四季度。這些動態導致年底批發商庫存增加約 2,000 萬美元，主要影響了 VIVITROL 和 ARISTADA。

Our fourth quarter results also reflected gross-to-net favorability primarily related to lower Medicaid and VA utilization and certain other credits. These factors drove a onetime gross-to-net benefit of approximately $12 million for VIVITROL and approximately $3 million for ARISTADA. Taken together, these inventory and gross-to-net dynamics resulted in a proprietary product revenue tailwind of approximately $35 million in Q4.

我們的第四季業績也反映出總淨利潤的有利因素，這主要與醫療補助和退伍軍人事務部的利用率降低以及某些其他信貸有關。這些因素導致 VIVITROL 的一次性毛淨收益達到約 1,200 萬美元，Aristada 的一次性毛淨收益達到約 300 萬美元。綜合起來，這些庫存和毛利與淨利的動態變化導致第四季專有產品收入順風增加約 3,500 萬美元。

Moving on to our manufacturing and royalty business. For the year, we reported manufacturing and royalty revenues of $474.1 million, primarily driven by royalties related to long-acting INVEGA products of $236.4 million and revenues from VUMERITY of $134 million.

繼續討論我們的製造和特許權業務。本年度，我們報告的製造和特許權使用費收入為 4.741 億美元，主要得益於與長效 INVEGA 產品相關的特許權使用費 2.364 億美元和 VUMERITY 的 1.34 億美元收入。

Now I'll turn to our full year 2024 operating expenses and our financial results from continuing operations. These results reflect the separation of our former oncology business, which was completed during the fourth quarter of 2023. Cost of goods sold were $245.3 million, compared to $253 million for the prior year. R&D expenses were $245.3 million compared to $270.8 million in the prior year. This consisted of focused investments in our neuroscience development programs, primarily related to the ALKS 2680 clinical program and support activities for our proprietary commercial products.

現在，我將談談我們 2024 年全年營運費用和持續經營的財務表現。這些結果反映了我們先前的腫瘤學業務的分離，該分離於 2023 年第四季度完成。銷售成本為 2.453 億美元，而上年為 2.53 億美元。研發費用為 2.453 億美元，而去年同期為 2.708 億美元。這包括對我們的神經科學發展項目的重點投資，主要涉及 ALKS 2680 臨床項目和我們專有商業產品的支援活動。

SG&A expenses were $645.2 million compared to $689.8 million in 2023 as we continue to invest in the growth of LYBALVI and focus on efficiency. Overall, the business drove significant profitability from continuing operations, generating GAAP net income of $372.1 million, non-GAAP net income of $494.4 million, and EBITDA of $452.4 million for the year.

由於我們繼續投資於 LYBALVI 的發展並注重效率，銷售、一般和行政費用為 6.452 億美元，而 2023 年為 6.898 億美元。總體而言，該業務透過持續經營獲得了可觀的盈利，全年創造了 3.721 億美元的 GAAP 淨收入、4.944 億美元的非 GAAP 淨收入和 4.524 億美元的 EBITDA。

Turning to our balance sheet. We ended the year in a strong financial position. As I outlined earlier, during the fourth quarter, [we've been predate] approximately $290 million of our outstanding debt, ending the year debt-free with approximately $825 million in cash and total investments. We continue to have $200 million of remaining share repurchase authorization. And going forward, we may opportunistically repurchase shares depending on market conditions and the capital needs of the business.

轉向我們的資產負債表。我們以強勁的財務狀況結束了這一財年。正如我之前所概述的，在第四季度，我們已經償還了約 2.9 億美元的未償還債務，到年底我們已經無債務，擁有約 8.25 億美元的現金和總投資。我們繼續擁有 2 億美元的剩餘股票回購授權。展望未來，我們可能會根據市場狀況和業務的資本需求適時回購股票。

In 2025, we plan to manage the business to deliver significant profitability and cash flow while investing in the growth opportunities that we believe will be the key drivers of shareholder value. During our third quarter earnings call, we previewed our expectation to generate EBITDA of greater than $200 million for 2025. And today, I'll provide more detailed financial expectations.

2025 年，我們計劃管理業務以實現顯著的獲利能力和現金流，同時投資我們認為將成為股東價值關鍵驅動力的成長機會。在我們的第三季財報電話會議上，我們預計 2025 年的 EBITDA 將超過 2 億美元。今天，我將提供更詳細的財務預期。

In addition, given the transformation of our business over the last several years and feedback we have received from shareholders, we are transitioning to an adjusted EBITDA metric going forward in lieu of non-GAAP net income, as we believe adjusted EBITDA better captures the dynamics of our underlying business.

此外，考慮到我們過去幾年業務的轉型以及從股東那裡收到的回饋，我們將轉向調整後的 EBITDA 指標，以取代非 GAAP 淨收入，因為我們認為調整後的 EBITDA 更能反映我們基礎業務的動態。

Our expectations were outlined in the press release and 8K issued this morning. Starting with the top line, we expect total revenues for 2025 to be in the range of $1.34 billion to $1.43 billion, driven primarily by net sales of our proprietary products in the range of $1.09 billion to $1.15 billion. As we previously disclosed, in 2025, we expect manufacturing and royalty revenues to decrease by approximately $215 million compared to 2024, reflecting the expiration of the INVEGA SUSTENNA US royalty in August 2024 and and the conclusion of certain legacy manufacturing revenues following the sale of our manufacturing business in Ireland last year.

我們的期望已在今天早上發布的新聞稿和 8K 中概述。從營收開始，我們預計 2025 年的總收入將在 13.4 億美元至 14.3 億美元之間，主要由專有產品淨銷售額（10.9 億美元至 11.5 億美元）的推動。正如我們之前披露的那樣，到 2025 年，我們預計製造和特許權使用費收入將比 2024 年減少約 2.15 億美元，這反映了 INVEGA SUSTENNA 美國特許權使用費於 2024 年 8 月到期以及去年出售愛爾蘭製造業務後某些遺留製造收入的結束。

Turning to expenses. Cost of goods sold are expected to be in the range of $185 million to $205 million, reflecting our streamlined manufacturing footprint. R&D expenses are expected to be in the range of $305 million to $335 million. This level of R&D spend is to accommodate our ongoing ALKS 2680 Phase II programs in narcolepsy and the planned initiation of the ALKS 2680 Phase II program in idiopathic hypersomnia and first-in-human studies for ALKS 4510 and ALKS 7290, our next orexin 2 receptor agonist candidate.

談到費用。預計銷售成本在 1.85 億美元至 2.05 億美元之間，反映了我們精簡的製造足跡。預計研發費用在3.05億美元至3.35億美元之間。這一水準的研發支出是為了適應我們正在進行的 ALKS 2680 發作性睡病 II 期計畫、計劃啟動的 ALKS 2680 特發性嗜睡症 II 期計畫以及 ALKS 4510 和 ALKS 7290（我們的下一個食慾素 2 受體激動劑候選藥物）的首次人體研究。

SG&A expenses are expected to be in the range of $655 million to $685 million, which reflects investments in the expansion of our psychiatry sales team, targeted investments in the promotional support for our commercial products, and continued focus on operational efficiency. We expect an effective tax rate of approximately 17% in 2025. We are committed to maintaining a robust cash-generating business and expect to deliver GAAP net income range of $175 million to $205 million. EBITDA in the range of $215 million to $245 million, and adjusted EBITDA in the range of $310 million to $340 million.

銷售、一般及行政費用預計在 6.55 億美元至 6.85 億美元之間，這反映了我們對精神病學銷售團隊擴張的投資、對我們商業產品的促銷支持有針對性的投資以及對營運效率的持續關注。我們預計 2025 年的有效稅率約為 17%。我們致力於保持強勁的現金創造業務，並預計實現 1.75 億美元至 2.05 億美元的 GAAP 淨收入。EBITDA 在 2.15 億美元至 2.45 億美元之間，調整後 EBITDA 在 3.1 億美元至 3.4 億美元之間。

As we look ahead to Q1, due to more pronounced seasonality related to the year-end ordering patterns in Q4 and the dynamics within our royalty and manufacturing portfolio that I previously outlined, I'll provide some additional color on quarterly trending expectations to facilitate modeling.

展望第一季度，由於第四季度年終訂購模式的季節性更加明顯，以及我之前概述的特許權使用費和製造組合內的動態，我將提供一些關於季度趨勢預期的額外信息，以促進建模。

In the first quarter of 2025, we expect our net sales from our proprietary commercial product portfolio to be in the range of $220 million to $240 million. This reflects our expectation of wholesaler inventory normalization related to the extra order cycle in Q4 and usual first quarter inventory drawdown patterns. Typical Q1 patient co-pay and deductible reset dynamics and historical demand matters.

2025 年第一季度，我們預計專有商業產品組合的淨銷售額將在 2.2 億美元至 2.4 億美元之間。這反映了我們對批發商庫存正常化的預期，這與第四季度的額外訂單週期以及第一季通常的庫存下降模式有關。典型的 Q1 患者共同支付和免賠額重置動態和歷史需求問題。

The royalty and manufacturing revenue will reflect the annual reset of the royalty tiers on the remaining long-acting INVEGA products, the conclusion of certain manufacturing revenue streams, and typical Q1 end market seasonality. We expect these factors will drive a sequential decrease of approximately $60 million compared to Q4.

特許權使用費和製造收入將反映剩餘長效 INVEGA 產品的特許權使用費等級的年度重置、某些製造收入流的結束以及典型的第一季終端市場季節性。我們預計這些因素將導致環比第四季減少約 6000 萬美元。

On the expense side, we expect cost of goods sold in the first quarter of 2025 to be down sequentially from the fourth quarter, consistent with historical Q1 sales patterns. For the first quarter of 2025, we expect R&D expenses to increase approximately $50 million sequentially from Q4, primarily driven by activities related to the ALKS 2680 Phase II programs in narcolepsy.

在費用方面，我們預計 2025 年第一季的銷售成本將較第四季環比下降，與歷史第一季銷售模式一致。2025 年第一季度，我們預計研發費用將比第四季環比增加約 5,000 萬美元，主要受 ALKS 2680 發作性睡病 II 期計畫相關活動的推動。

And study start-up activities for the idiopathic hypersomnia Phase II. We expect SG&A expenses to be similar to the first quarter of 2024 and reflecting investments in the LYBALVI promotional activities and expansion of our psychiatry field sales force during the quarter.

並針對特發性嗜睡症第二期進行研究啟動活動。我們預計銷售、一般及行政費用將與 2024 年第一季相似，並反映了本季對 LYBALVI 促銷活動的投資以及我們精神科現場銷售隊伍的擴張。

Taken altogether, we expect Q1 to be closer to breakeven on an EBITDA basis with total revenues and profitability to increase significantly in the second quarter and remain fairly consistent overall in the second half of the year. These expectations for quarterly trending are reflected in the full year financial expectations that I outlined a few moments ago.

綜合來看，我們預計第一季的 EBITDA 將更接近損益平衡，第二季的總營收和獲利能力將大幅增加，下半年整體將保持相當穩定。這些對季度趨勢的預期反映在我剛才概述的全年財務預期中。

We enter 2025 well positioned financially with a strong balance sheet, a substantial commercial business, and a continued focus on operational efficiency and profitability. We are investing in the initiatives that we believe will drive the future growth of the company and significant opportunities to create value for shareholders.

進入 2025 年，我們將擁有良好的財務狀況，擁有強勁的資產負債表、龐大的商業業務，並持續專注於營運效率和獲利能力。我們正在投資那些我們認為將推動公司未來成長和為股東創造價值的重大機會的計劃。

With that, I'll now hand the call to Todd for a review of the commercial portfolio.

說完這些，我現在將電話交給托德來審查商業投資組合。

Thank you, Blair, and good morning, everyone. 2024 was an important year of execution of our commercial strategy, and I am pleased that we achieved our expectations of proprietary net sales in excess of $1 billion in 2024, which reflected 18% year-over-year growth. Blair has taking you through the net sales performance, so from my remarks, I will focus on underlying demand trends in our strategic focus areas and expectations for 2025.

謝謝你，布萊爾，大家早安。 2024 年是我們執行商業策略的重要一年，我很高興我們實現了 2024 年專有淨銷售額超過 10 億美元的預期，年增 18%。布萊爾向您介紹了淨銷售業績，因此在我的演講中，我將重點放在我們戰略重點領域的潛在需求趨勢以及對 2025 年的期望。

Starting with VIVITROL. In 2024, VIVITROL net sales grew 14% year-over-year, driven by 6% underlying demand growth. This demand growth reflects strong traction in alcohol-dependent indication slightly offset by demand in the opioid dependence indication. The alcohol attendance indication represented approximately 75% of VIVITROL volume and is where we focus our promotional efforts. As we look ahead to 2025, we expect VIVITROL demand to grow at mid-single-digit rates and net sales to be in the range of $440 million to $460 million.

從 VIVITROL 開始。2024 年，VIVITROL 淨銷售額年增 14%，這得益於 6% 的潛在需求成長。這種需求成長反映了酒精依賴症的強勁成長，但對阿片類藥物依賴症的需求略有抵消。酒精飲料銷售量約佔 VIVITROL 銷售量的 75%，也是我們促銷最大的部分。展望 2025 年，我們預期 VIVITROL 的需求將以中位數個位數成長，淨銷售額將介於 4.4 億至 4.6 億美元之間。

Turning to our psychiatry franchise, which includes both ARISTADA and LYBALVI, we are focused on delivering growth across the franchise and are making strategic investments that we believe will drive underlying demand and profitability. For the ARISTADA product family, in 2024, ARISTADA net sales grew 6% year-over-year. In 2025, we expect underlying demand to remain fairly consistent compared to last year and ARISTADA net sales to be in the range of $335 million to $355 million.

談到我們的精神病學特許經營權，其中包括 Aristada 和 LYBALVI，我們專注於實現整個特許經營權的增長，並正在進行戰略投資，我們相信這將推動潛在的需求和盈利能力。對於AISTADA產品系列，2024年，AISTADA淨銷售額年增6%。到 2025 年，我們預計基本需求將與去年相比保持相當穩定，Aristada 淨銷售額將在 3.35 億美元至 3.55 億美元之間。

In 2024, net sales of LYBALVI grew 46% year-over-year, primarily driven by underlying TRx growth of 39%, with growth coming from both the schizophrenia and bipolar 1 disorder medications. Our promotional and direct-to-consumer advertising activities will continue to focus on driving adoption in both indications, utilizing tailored approaches to effectively target each segment. During the year, we made significant progress in enhancing the access profile for LYBALVI in the commercial payer channel with additional plans taking effect in January of this year.

2024 年，LYBALVI 的淨銷售額年增 46%，主要得益於基礎 TRx 成長 39%，成長來自精神分裂症和雙相情感障礙 1 型藥物。我們的促銷和直接面向消費者的廣告活動將繼續專注於推動兩種適應症的採用，並利用客製化方法有效地針對每個細分市場。今年，我們在增強 LYBALVI 在商業付款人管道的存取配置方面取得了重大進展，並將於今年 1 月實施其他計劃。

Looking ahead in 2025, we expect these improvements will lead to slight widening of gross-to-net adjustments to the [mid-30s] as we previously outlined. We are pleased with LYBALVI's access profile today and will remain focused on additional opportunities to enhance our coverage going forward.

展望 2025 年，我們預期這些改善將導致毛利率與淨利率的調整幅度略微擴大至我們先前所概述的 [30 年代中期]。我們對 LYBALVI 目前的訪問情況感到滿意，並將繼續關注更多機會以增強我們未來的覆蓋範圍。

In 2025, we expect LYBALVI demand to grow by approximately 25% year-over-year and net sales to be in the range of $320 million to $340 million. For both LYBALVI and ARISTADA, as we enter 2025, we will continue to focus on the competitive dynamics in the antipsychotic space as we invest in and expand our psychiatry sales team in order to preserve a competitive share of voice for LYBALVI and reaccelerate growth for ARISTADA.

2025 年，我們預計 LYBALVI 的需求將年增約 25%，淨銷售額將在 3.2 億至 3.4 億美元之間。對於 LYBALVI 和 ARISADA，進入 2025 年，我們將繼續關注抗精神病領域的競爭動態，同時投資並擴大我們的精神病學銷售團隊，以保持 LYBALVI 的競爭份額並重新加速 ARISADA 的成長。

We plan to complete our sales force expansion in the first quarter and expect contributions from the new sales positions to be tangible a few quarters from now. With the expansion of the sales team and enhanced access profile for LYBALVI and a strong value proposition for both brands, we believe we are well positioned to achieve our 2025 goals for ARISTADA and LYBALVI. We look forward to sharing our progress with you.

我們計劃在第一季完成銷售團隊的擴張，並預計新銷售職位的貢獻將在幾個季度後顯現出來。隨著銷售團隊的擴大、LYBALVI 存取權限的增強以及兩個品牌的強大價值主張，我們相信我們有能力實現 ARISTADA 和 LYBALVI 的 2025 年目標。我們期待與您分享我們的進展。

With that, I'll pass the call back to Rich.

說完這些，我就把電話轉回給里奇。

Okay. Thank you, Todd. So we operate in commercial environments that require particular capabilities and scale. Our strategy and our investments focus on growth and profitability while enabling broad access to our medicines. We're well positioned there to be successful.

好的。謝謝你，托德。因此，我們在需要特定能力和規模的商業環境中運作。我們的策略和投資注重成長和獲利，同時確保我們的藥品能夠廣泛使用。我們已做好準備，將獲得成功。

Our commercial business is the economic engine of the company. Its cash flows give us the non-dilutive capital to invest aggressively in our development pipeline while maintaining profitability. And that pipeline is now at a stage where it has the potential to be transformative for the company. We see that becoming clear in 2025 with planned Phase II data readouts for ALKS 2680, in narcolepsy type 1, and narcolepsy type 2.

我們的商業業務是公司的經濟引擎。它的現金流為我們提供了非稀釋性資本，使我們可以在保持獲利能力的同時積極投資於我們的開發管道。目前，該管道已經到達了一個有可能為公司帶來改變的階段。我們看到，隨著 ALKS 2680 在 1 型發作性睡病和 2 型發作性睡病方面的 II 期數據讀取，這一點將在 2025 年變得清晰起來。

ALKS 2680 is our novel orexin 2 receptor agonist. From the outset, we designed it with a future competitive profile in mind, incorporating things that we've learned, making medicines for patients in the real-world setting. For ALKS 2680, the goal has been to offer simple, once-daily dosing and importantly, a range of doses to accommodate patients across narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. Advancing multiple doses would offer patients and physicians the potential to adjust dosing to individual needs and preference, which is an important feature across many CNS disorders.

ALKS 2680 是我們新型的食慾素 2 受體激動劑。從一開始，我們在設計它時就考慮到了未來的競爭力，結合我們所學到的東西，在現實世界中為患者製造藥物。對於 ALKS 2680，目標是提供簡單的每日一次劑量，重要的是，提供一系列劑量以適應 1 型發作性睡病、2 型發作性睡病和特發性嗜睡症患者。提前多次劑量治療將為患者和醫生提供根據個人需求和偏好調整劑量的潛力，這是許多中樞神經系統疾病的重要特徵。

Let me spend a second on these hypersonic disorders. Orexin is the master regulator of wakefulness. Narcolepsy type 1 is characterized by the absence or loss of orexin neurons in the brain. In NT1 orexin-2 receptor agonist has the potential to replace the missing neuropeptide and restore normal wakefulness. Clinical data in NT1 provides strong evidence of this activity.

請容許我花一點時間來談論這些超音速疾病。Orexin 是覺醒的主要調節劑。1 型嗜睡症的特徵是大腦中食慾素神經元的缺失或流失。在 NT1 中，食慾素-2 受體激動劑有可能取代缺失的神經肽並恢復正常的覺醒狀態。NT1 中的臨床數據為此活動提供了有力的證據。

Narcolepsy type 2 and idiopathic hypersomnia are associated with more normal orexin 2 [and 3] but may also be associated with average signaling of the orexin system. A foundation of clinical data suggests that orexin 2 receptor agonist can promote wakefulness in these patients, too, data from our ALKS 2680 Phase Ib study and an early proof-of-concept study connected by others, both demonstrated significant improvements in [weight loss] in these disorders. At sufficient doses, we believe based on data observed the orexin 2 receptor agonist may have potential significant utility in NT2 and IH.

2 型發作性睡病和特發性嗜睡症與更正常的食慾素 2 [和 3] 有關，但也可能與食慾素系統的平均訊號傳導有關。大量臨床數據表明，食慾素 2 受體激動劑也可以促進這些患者的覺醒，我們 ALKS 2680 Ib 期研究的數據以及其他人關聯的早期概念驗證研究的數據均表明這些疾病的 [減肥] 有顯著改善。根據觀察到的數據，我們相信，在足夠的劑量下，食慾素 2 受體激動劑可能在 NT2 和 IH 中具有潛在的顯著效用。

From a regulatory and development perspective, we're advancing ALKS 2680 pursuant to a strategy design with the end goal in mind, which is FDA approval and competitive position. With proof-of-concept data from a robust Phase Ib program in patients with narcolepsy in hand, last year, we moved into well-powered, parallel design confirmatory Phase II studies in NT1 and NT2. Each study is designed to enroll 80 patients.

從監管和發展的角度來看，我們根據策略設計來推進 ALKS 2680，最終目標是獲得 FDA 批准和競爭地位。去年，我們獲得了針對發作性睡病患者的強有力的 Ib 期計劃的概念驗證數據，並進入了 NT1 和 NT2 中強有力的、平行設計的確認性 II 期研究。每項研究旨在招募 80 名患者。

These studies will represent a significant additional increment of data for the entire field. When we're done, we'll have 160 patients worth of data testing a range of doses over a multi-week period in the outpatient setting. These are studies sufficient design and duration to more fully characterize safety, tolerability, efficacy, and dose response. These data will inform our ALKS 2680 Phase III design and also begin to elaborate our potential competitive positioning in the class.

這些研究將為整個領域帶來大量的額外數據。當我們完成後，我們將擁有 160 名患者的數據，這些患者在門診環境中經過數週的一系列劑量測試。這些研究的設計和持續時間足夠，可以更全面地描述安全性、耐受性、有效性和劑量反應。這些數據將為我們的 ALKS 2680 第三階段設計提供信息，並開始闡述我們在該類別中的潛在競爭地位。

I'll give you a quick update on the progress we're making with Vibrance-1 and Vibrance-2, our Phase II narcolepsy studies we initiated last year. We've made significant progress with site initiations and enrollment and I'm pleased with our momentum. We're now enrolling patients in the US, EU, and Australia. And we expect data from both of these studies in the second half of this year. As we exit this quarter, this first quarter, we should have sufficient line of sight to estimate completion time with more specificity.

我將向您簡要介紹我們去年啟動的第二階段嗜睡症研究 Vibrance-1 和 Vibrance-2 的進展。我們在網站啟動和註冊方面取得了重大進展，我對我們的發展勢頭感到滿意。我們目前正在招募美國、歐盟和澳洲的患者。我們預計這兩項研究的數據將在今年下半年獲得。當我們結束這個季度，也就是第一季時，我們應該有足夠的視線來更具體地估計完成時間。

In idiopathic hypersomnia, we submitted an IND to the Division of Neurology at FDA, and we're expecting to initiate that Phase II study in the early spring. This study will be known as Vibrance-3, and it will share structural features of the narcolexty studies. Randomized, placebo-controlled, double-blind parallel design for 8 weeks.

對於特發性嗜睡症，我們向 FDA 神經病學部門提交了 IND，預計將在早春啟動第二階段研究。這項研究將被命名為 Vibrance-3，它將與發作性睡病治療研究共享結構特徵。隨機、安慰劑對照、雙盲平行設計，為期 8 週。

The doses will mirror our NT II study at 10, 14, and 18 milligrams. Consisting with pivotal studies that have supported approval of idiopathic hypersomnia, we'll use the sport sleepiness scale as the primary endpoint and the idiopathic hypersomnia severity scale or IHSS as the key secondary end point.

劑量將與我們的 NT II 研究相似，分別為 10、14 和 18 毫克。與支持核准特發性嗜睡症的關鍵研究一致，我們將使用運動嗜睡量表作為主要終點，以特發性嗜睡症嚴重程度量表或 IHSS 作為關鍵次要終點。

So in conclusion, for both our narcolepsy and NIH, we see the structure and execution of the Phase II program as the springboard for Phase III registration and commercial positioning. We are planning for success and preparing for the [pivotal] program with manufacturing, protocol design, and regulatory work streams all underway. It's going to be exciting and a busy year.

因此，總而言之，對於我們的嗜睡症和 NIH，我們將 II 期計劃的結構和執行視為 III 期註冊和商業定位的跳板。我們正在為成功規劃和準備[關鍵]計劃，製造、協議設計和監管工作流程均在進行中。這將是令人興奮又忙碌的一年。

So with that, I'll turn the call back to Sandy for the Q&A.

因此，我將把電話轉回給桑迪進行問答。

Melissa, we'll open the call for Q&A now please.

梅麗莎，我們現在開始問答環節。

(Operator Instructions)

（操作員指令）

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

I just had one on the orexin program. I was curious, with these studies now well underway and specifically related to the NT II study. I was wondering how close you guys are monitoring adverse events, retention, things like that on a blinded basis, especially as one of the questions to the class is how does tolerability look in larger studies outside of NT1. So any color you could provide there if it is applicable, would be helpful. And maybe just speak to your confidence again in the therapeutic index across broader populations. Thank you.

我剛剛參加了一個 orexin 計劃。我很好奇，這些研究現在已經順利進行，並且與 NT II 研究具體相關。我想知道你們在盲法基礎上對不良事件、保留率等情況的監測程度有多高，尤其是課堂上的一個問題是，在 NT1 之外的更大規模研究中，耐受性如何。因此，如果適用的話，您提供的任何顏色都會很有幫助。也許只是想再次談談您對更廣泛人群的治療指數的信心。謝謝。

Hey Paul, it's Rich. I'll take that one. So obviously, these are blinded studies, multicenter, multi-country, but we monitor safety on an ongoing basis and not just ourselves, our team, but we have a DSMB that meets regularly to look at that. Remember, the structure of the design is a six-week double-blind period with a seven-week extension thereafter.

嘿，保羅，我是里奇。我要那個。顯然，這些都是盲法研究、多中心、多國家研究，但我們會持續監測安全性，而且不僅僅是我們自己、我們的團隊，而且我們還有一個 DSMB 定期開會來研究這個問題。請記住，設計的結構是六週的雙盲期，隨後是七週的延長期。

And we expect a high degree of retention throughout the whole program, and we haven't seen anything to dissuade us from that at this point. As I said in the prepared remarks, I think that the logic and the data supporting NT2 is pretty strong, recognizing these slightly higher doses, what we saw in our Phase Ib program is clear dose response, notwithstanding the baseline variability that you might see in NT2. So we're encouraged at this point and we look forward to [being] study.

我們期望整個專案的保留率很高，目前我們還沒有看到任何阻礙我們實現這一目標的事情。正如我在準備好的評論中所說，我認為支持 NT2 的邏輯和數據非常強大，認識到這些略高的劑量，我們在 Ib 期計劃中看到的是明確的劑量反應，儘管您可能會在 NT2 中看到基線變異。因此，我們現在感到很受鼓舞，並期待進一步的研究。

Great, thank you.

太好了，謝謝。

Charles Duncan, Cantor Fitzgerald.

查爾斯鄧肯、康托菲茨傑拉德。

Hey, good morning, Rich and team, congrats on a good year of progress. I wanted to ask a quick commercial question and then a follow-up on the pipeline. With regard to the commercial setting, I guess I'm wondering if you are -- not if you're considering, what you're considering in terms of competitive dynamics for LYBALVI and ARISTADA given BMS and J&J, becoming more active in the space. And I think Todd mentioned expanding the sales force. Can you give some color on, call it, the magnitude of that expansion?

嘿，早上好，Rich 和團隊，祝賀你們取得了豐碩的進步。我想問一個簡單的商業問題，然後跟進一下管道的狀況。關於商業環境，我想知道您是否正在考慮，鑑於 BMS 和 J&J 在該領域變得更加活躍，您對 LYBALVI 和 ARISADA 的競爭動態有何看法。我認為托德提到了擴大銷售團隊。能否具體說明一下這種擴張的程度？

Yeah, absolutely, Charles. This is Todd. I'll take that as well. We look at the competitive dynamics all the time. The benefit to our portfolio would be market growth as more companies invest in the category, which we think is a good thing. But it doesn't really change the strategy that we have. We're going to -- in 2025, [actions] that will again show really strong demand growth for LYBALVI approximately 25%.

是的，絕對是，查爾斯。這是托德。我也會接受這個。我們始終關注競爭動態。隨著越來越多的公司投資於該類別，我們的投資組合將受益於市場成長，我們認為這是一件好事。但它並沒有真正改變我們的戰略。我們將在 2025 年採取行動，再次顯示對 LYBALVI 的強勁需求成長，約 25%。

We're also going to be expanding our sales force, as I said in my prepared remarks, that's been something that we've been watching and preparing for a while. And that's really intended to make sure that we maintain really strong competitive share of voice and that we're able to not only compete effectively, but really maximize the portfolio. As I said in my prepared remarks, it's about demand growth for us, but also profitability. And I think we're right on track for that in 2025.

我們還將擴大我們的銷售隊伍，正如我在準備好的演講中所說的那樣，這是我們一直在關注和準備的事情。這實際上是為了確保我們保持真正強大的競爭份額，並且我們不僅能夠有效競爭，而且我們能夠真正最大化投資組合。正如我在準備好的演講中所說，這對我們來說不僅關乎需求成長，也關乎獲利能力。我認為我們在 2025 年就有望實現這一目標。

I mentioned the size of the expansion.

我提到了擴張的規模。

Yeah, absolutely. The size of the sales force expansion we're looking at, we're going to add up approximately 80 representatives. They'll be online at the end of this quarter, and we expect them to be operational in Q2. All of my experience tells me it just takes a couple of quarters for that to play out. They get trained and get into the marketplace to start educating HCP. So our expectation is we'll start to see the benefit of that expansion in the latter part of the year.

是的，絕對是如此。我們正在考慮擴大銷售團隊的規模，將增加約 80 名銷售代表。它們將於本季末上線，我們預計它們將在第二季投入營運。我所有的經驗告訴我，這只需要幾個季度就能實現。他們接受培訓並進入市場開始教育 HCP。因此，我們預計我們將在今年下半年開始看到擴張帶來的好處。

Very good. That's helpful. Quickly on Vibrance-1 and 2, realize that by end of the quarter, you'll give more guidance. But when you consider the NT1 patient population versus NT2, can you provide some color on the interest in the two studies? And could they read out at the same time or is NT1 ahead of NT2 or reverse?

非常好。這很有幫助。快速了解 Vibrance-1 和 2，並意識到到本季末，您將提供更多指導。但是，當您考慮 NT1 患者群體與 NT2 患者群體時，您能否提供一些關於對這兩項研究的興趣的詳細資訊？它們能同時讀出來嗎？還是 NT1 領先 NT2 或相反？

It's hard to say. It sort of [jockey for the lead and Hesh], the two studies get up and running. NT2 started a little bit later. But with little competition that ramp inside initiations ramp really, really quickly. Vibrance-1, NT1 study now is open in multiple countries and coming out of the Christmas holidays. We're enrolling aggressively in that one now. So it's too early to say, but I think our hope is that they finish roughly at the same time in the second half of the year, hopefully give you more precision probably on the next call.

這很難說。這有點像 [爭奪領先和 Hesh]，兩項研究開始順利進行。NT2 開始得稍晚。但由於競爭很少，內部啟動的升級速度非常非常快。Vibrance-1、NT1 研究現已在多個國家開放，並即將結束聖誕假期。我們現在正在積極招收這方面的人員。所以現在說還為時過早，但我認為我們希望他們能在下半年大致同一時間完成，希望在下次電話會議中能給你更精確的信息。

Excellent, thanks.

非常好，謝謝。

And Charles, let's just say, as a general matter, the interest in the community of the [orexin 2] receptor agonist is extremely high, in NT1, NT2, and IH. And I think that, that's the sea change we've seen over the last year or so as more and more practitioners get aware of the developments that are happening in the field, I think the excitement level around the category is building.

查爾斯，我們可以這麼說，一般來說，社區對 NT1、NT2 和 IH 中 [orexin 2] 受體激動劑的興趣非常高。我認為，這是我們在過去一年左右看到的巨大變化，隨著越來越多的從業者意識到該領域正在發生的發展，我認為圍繞著該類別的興奮程度正在上升。

Umer Raffat, Evercore ISI.

Umer Raffat，Evercore ISI。

Hi guys, thanks for taking my question. I have two here, if I may. First, a quick one on orexin. Rich, could you remind us if you're expecting the type 2 study, the Narcolepsy type 2 to come before type 1 or not? I know you had commented on the recruitment rates on both trials previously. So I'm just curious.

大家好，感謝你們回答我的問題。如果可以的話，我這裡有兩個。首先，簡單介紹一下 orexin。Rich，您能否提醒我們，您是否預期第 2 型研究結果中，2 型嗜睡症會先於第 1 型出現？我知道您之前曾對兩次試驗的招募率進行過評論。所以我只是很好奇。

Secondly, on LYBALVI, I'm just still trying to work my way through this. There's -- if we stick to the current gross-to-net and if we stick to the cadence of Rx growth we've seen in 3Q and 4Q, it could imply a number which is below even the low end of your guidance. But on the flip side, we know there was a little bit of gross net delta as well as some inventory effects that were also helping. So if you could just walk us through some of that, that would be very helpful. Thank you.

其次，關於 LYBALVI，我仍在努力解決這個問題。如果我們堅持當前的毛利與淨利的比率，並堅持我們在第三季和第四季看到的 Rx 成長節奏，那麼它可能意味著一個低於您指導值低端的數字。但另一方面，我們知道有一點淨增量以及一些庫存效應也有幫助。因此，如果您能向我們介紹其中的一些內容，那將會非常有幫助。謝謝。

[Well, let me start with the one]. The NT2 study is enrolling well, and the NT1 study is enrolling well. And the big change since we talked about last coming out of holiday is that lot of our European sites in the NT1 study are up and running now in screening patients. So I think it's a horse race between the two of them. We'll have more precision on the actual completion date in a couple of months' time.

[好吧，讓我先從一個]。 NT2 研究的招募情況良好，NT1 研究的招募情況也良好。自從我們上次假期結束後談到這一點以來，最大的變化是，我們參與 NT1 研究的許多歐洲站點現在都已開始篩檢患者。所以我認為這是他們兩人之間的賽馬。幾個月後我們將更準確地確定實際完成日期。

Yeah. This is Todd. I'll comment on LYBALVI. So if you look at the Q4 dynamics from LYBALVI, we saw approximately 5% TRx growth, which was relatively consistent with Q3, which is a healthy sign. That was really driven by continued expansion with HCP breadth. Year-over-year ACP breadth, our customer breadth grew by approximately 27%. So it's a really good leading indicator on the health of the brand and how it's expanding.

是的。這是托德。我會對 LYBALVI 發表評論。因此，如果您查看 LYBALVI 的第四季度動態，我們看到 TRx 增長約為 5%，這與第三季度相對一致，這是一個健康的信號。這實際上是由 HCP 廣度的持續擴展所推動的。與去年同期的 ACP 廣度相比，我們的客戶廣度成長了約 27%。因此，它是衡量品牌健康狀況和擴張情況的非常好的領導指標。

Going into our expectation is that, again, we're going to continue to see strong demand growth. There is going to be the typical demand patterns that Blair mentioned in Q1. So we would expect that but we expect building out of that in Q2, Q3, and Q4. And it's really going to be driven by our sales force expansion. Once we do the sales force expansion, our total footprint will be approximately 400 sales representatives, which is a is a really good, strong share of voice, and that's going to be supported with expanded market access.

我們的預期是，我們將繼續看到強勁的需求成長。布萊爾在第一季提到的典型需求模式將會出現。所以我們預計這一點，但我們預計這一點將在第二季、第三季和第四季得到體現。這實際上將受到我們銷售團隊擴張的推動。一旦我們擴大銷售隊伍，我們的總規模將達到約 400 名銷售代表，這是一個非常好的、強大的話語權，而且這將透過擴大市場准入得到支持。

So in Q1, we think the market access position for gross-to-net can expand to around mid-30%s. And then it will modulate down in Q2, Q3 and Q4. So the full year will be around that mid-30% range. And that's a really important attribute for how we see demand growth because as I said in my prepared remarks, we are entering the year with even a stronger market access position, more patients in commercial, more patients in Medicare Part D have access, and we think that's going to be a big driver of our demand growth for '25.

因此，我們認為在第一季度，毛利率與淨利率的市場准入比例可以擴大到 30% 左右。然後它將在 Q2、Q3 和 Q4 中向下調製。因此全年成長率將在 30% 左右。這對我們如何看待需求成長是一個非常重要的屬性，因為正如我在準備好的發言中所說，我們在今年將擁有更強大的市場准入地位，更多的商業患者、更多的聯邦醫療保險 D 部分患者可以獲得服務，我們認為這將成為我們25年需求增長的一大驅動力。

Akash Tiwari, Jefferies.

Akash Tiwari，傑富瑞（Jefferies）。

Hey, This is Amy on for Akash. So on OX2, what's your confidence that ALKS 2680 can differentiate on safety versus TAK-861 in NT1? And what do you think the bar is?

嘿，我是 Akash 的 Amy。那麼在 OX2 上，您對 ALKS 2680 在安全性上與 NT1 中的 TAK-861 有所區別有多大信心？您認為酒吧是什麼？

And another one, if we can. Some of your competitors in the OX2 space are alluding to the ability to proceed into Phase III trials with an expedited Phase IIa. What do you think the FDA wants from their Phase II studies when it came to dose exploration in end. Thanks so much.

如果可以的話，再來一個。OX2 領域的一些競爭對手暗示能夠透過加速 IIa 期試驗進入 III 期試驗。當最終進行劑量探索時，您認為 FDA 想要從其 II 期研究中得到什麼？非常感謝。

Hi Amy. it's Rich. I'm afraid I won't give to give you a whole lot of information about other people's programs. So I'll just tell you about our. The whole point of our Phase II design is by this design, i.e., 80 patients multi-week parallel design with a primary endpoint of six weeks, followed by an open-label safety evaluation with dose ranging is to establish the safety, tolerability, efficacy dose response profile in a rigorous way. So when we complete those studies, we'll have a very, very clear picture of our drug, and then we'll be able to compare it to any other drug that is a similar stage of development.

你好，艾米。很豐富。恐怕我無法向您提供有關其他人的程序的大量資訊。所以我只會告訴你我們的。我們 II 期設計的全部要點就是透過這種設計，即對 80 名患者進行多周平行設計，以六週為主要終點，然後進行劑量範圍的開放標籤安全性評估，以嚴格的方式建立安全性、耐受性和療效的劑量反應曲線。因此，當我們完成這些研究時，我們將對我們的藥物有一個非常清晰的了解，然後我們將能夠將其與處於類似開發階段的任何其他藥物進行比較。

In terms of particular safety, I [mean my earlier comment] stands, I think until we have the Phase II data, we won't be able to say how we're covering we believe that the program already differentiated is a priority, given the range of doses that we've shown, the dosing flexibility and the overall safety and tolerance we demonstrated in Ib.

就特定安全性而言，我（指我之前的評論）的立場是，我認為在我們獲得第二階段的數據之前，我們將無法說出我們如何覆蓋我們認為已經差異化的計劃是一個優先事項，因為我們已經展示的劑量範圍、劑量靈活性以及我們在 Ib 中展示的整體安全性和耐受性。

All of that needs to be reperpetulated and expanded in Phase II and then we'll have a clear picture. But I think categorically, between ourselves and others in the entity receptor and its class, it's striking that the overall tolerability we've all demonstrated is largely mild to moderate transient side effects with pretty significant and profound efficacy benefits for patients.

所有這些都需要在第二階段重新開始和擴展，然後我們才會有一個清晰的圖像。但我認為，從類別上看，我們自己和實體受體及其類別中的其他人之間，令人驚訝的是，我們都表現出的整體耐受性主要是輕度到中度的短暫性副作用，但對患者俱有相當顯著和深遠的療效益處。

Got it. Thanks so much.

知道了。非常感謝。

Jessica Fye, JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

Hey guys, good morning. Thanks for taking my question. A question on the 2025 guidance. What does that contemplate for INVEGA TRINZA as it relates to any risk of generic entry? And where does that litigation stand? And can you maybe characterize how much it contributes to the royalty revenue line? Thank you.

大家早安。感謝您回答我的問題。關於 2025 年指導方針的一個問題。這對 INVEGA TRINZA 來說意味著什麼，因為它與仿製藥進入的風險有關？那麼該訴訟的現況如何？您能否描述一下它對特許權使用費收入的貢獻有多大？謝謝。

Yes. Thank you for the question, Jessica. It's Blair. I think as we move into the beginning of the year, we have a little bit of dynamics as associates with INVEGA, recognizing that the US royalty expired in August of last year. So we'll be resetting to the lower rates as we move into Q1 of this year. And then we'll be achieving royalties moving forward, ex-US through 2026 and then the rest of the [CABENUVA] are no longer acting through 2030. So the INVEGA component of our overall say, manufacturing and royalty line is typically in the range of about 40% to 50% depending on where you are moving forward.

是的。謝謝你的提問，潔西卡。是布萊爾。我認為，隨著我們進入年初，作為 INVEGA 的合作夥伴，我們有一些動態，認識到美國特許權使用費已於去年 8 月到期。因此，進入今年第一季時，我們將重新調整利率至較低的水平。然後，我們將在未來獲得特許權使用費，除美國外，直到 2026 年，然後其餘的 [CABENUVA] 將不再代理到 2030 年。因此，我們整體話語權、製造和特許權使用費線中的 INVEGA 成分通常在 40% 到 50% 左右，具體取決於您未來的發展方向。

Thank you.

謝謝。

Chris Shibutani, Goldman Sachs.

高盛的 Chris Shibutani。

Thank you and good morning. Two maybe broader questions. One, in terms of thinking about clinical development risks for assets for the neuroscience. We've certainly always known that it's very difficult. There's been some recent industry examples where it's been kind of characteristic. Rich, you and your team have been no strangers to going through this. The journey has been long. What are you putting in place with the orexin program that you think informs and helps mitigate some of the risk?

謝謝，早安。兩個可能更廣泛的問題。一、考慮神經科學資產的臨床開發風險。我們當然一直都知道這非常困難。最近，業界出現了一些相當有特色的例子。里奇，你和你的團隊對這樣的事情並不陌生。旅途很長。您認為，您在食慾素計畫中採取了哪些措施，可以指導並幫助減輕一些風險？

And then second, Mark, a broad policy related question, Rich, again, you have had seats at some important tables thinking about the implications of health care policy on your business. And I would really appreciate if you could opine on a couple of points, perhaps if I could touch upon NIH-related funding implications on research, tariffs, IRA, a couple of the big pictures, which you have been helpful in the past look to get your insights as it relates to Alkermes and perhaps broadly to the industry. Thank you.

第二，馬克，一個廣泛的政策相關問題，里奇，你再次坐在一些重要的桌子上思考醫療保健政策對你的業務的影響。如果您能就幾個問題發表意見，我將不勝感激，也許我可以談談 NIH 相關的資金對研究、關稅、IRA 等幾個大局的影響，您過去對這些問題很有幫助，我可以就這些問題獲得您對 Alkermes 乃至整個行業的見解。謝謝。

Morning Chris. First, on the clinical development risk, which is sort of endemic -- when we think about CNS are you think about clinical development risk and actually expansion of that risk between Phase II and Phase III, that's part of the attractiveness of the orexin program. That often -- that condition that I just described is often what you find in psychiatric studies where the endpoints are things like PANS or HAMD or MADRS, where you're asking patients how they feel on an ongoing basis with the primary analysis happening often at a time point where you have huge placebo response as patients respond to care in the context of a clinical trial.

早上好，克里斯。首先，關於臨床開發風險，這種風險是一種地方性風險——當我們考慮 CNS 時，您會考慮臨床開發風險以及 II 期和 III 期之間風險的實際擴展，這是 orexin 計劃的吸引力之一。我剛才描述的那種情況通常就是精神病學研究中經常會發現的情況，其終點是 PANS 或 HAMD 或 MADRS 之類的內容，您會持續詢問患者的感受，而主要分析通常會在患者在臨床試驗中對治療產生反應時出現巨大安慰劑反應的時間點進行。

If you contrast that in something like narcolepsy type 1, where patients are washed out of all of their medicines, they are highly symptomatic at the data randomization. And they receive a really effective medicine. the placebo response is much more muted, if at all. So it's one of the reasons we are able to see a P-value with such a small number of patients in our Ib study. We expect that to continue into Phase II and into Phase III.

如果將其與 1 型發作性睡病之類的疾病進行對比，患者會失去所有藥物，並且在數據隨機化時會出現嚴重的症狀。他們得到了真正有效的藥物。安慰劑效應即使有，也非常微弱。所以這是我們能夠在 Ib 研究中如此少的患者中看到 P 值的原因之一。我們預計這一趨勢將持續到第二階段和第三階段。

And for that reason, we see Phase II as being very, very indicative of what we would expect to see in a replicate Phase III study. And that's why we've powered them so much and make them look as much like pivotal studies as you would want to see in Phase II.

因此，我們認為第二階段的研究非常能夠顯示我們期望在第三階段的重複研究中看到的結果。這就是為什麼我們對它們提供如此多的動力，並使它們看起來就像您希望在第二階段看到的關鍵研究一樣。

The policy questions along -- [I won't bore] with everything about it, but the overall admonishment is that it's very fluid right now, as you would know. Going down your list, NIH funding is something that I think is -- it's going to be focused and be focused on intramural funding at NIH; extramural is just so important for the public health and such a track record being valuable. But I think that there's going to be real scrutiny on efficiency and allocation of capital.

關於政策的問題——[我不會無聊地]談論所有相關問題，但總體警告是，正如你所知，目前政策非常不穩定。按照你的列表，我認為 NIH 資金將主要集中在 NIH 的內部資助上；校外對於公共衛生非常重要，這樣的記錄很有價值。但我認為，將會對資本的效率和分配進行真正的審查。

Tariffs. I think that we've done a tariff analysis on our own business, just given the way our supply chain is configured we don't have a major exposure to tariffs. And I think they will all wait to see how significantly how sensibly those are implemented.

關稅。我認為我們已經對自己的業務進行了關稅分析，考慮到我們的供應鏈配置方式，我們不會受到重大的關稅影響。我認為他們都會等待，看看這些措施的實施效果如何、是否合理。

Fixes to the IRA, I think are going to be problematic. I think there's some rifle shot fixes that you could anticipate. But I think in the context of reconciliation and all the other moving parts, I don't think they're a top priority right now, but I think there are some rifle shots that are possible that you can always characterize as fixes to the law as opposed to a complete rewiring of [the law].

我認為，對 IRA 的修復將會出現問題。我認為您可以預測一些步槍射擊修復。但我認為，在和解和所有其他活動部分的背景下，我不認為這些是目前的首要任務，但我認為有一些可能的槍擊事件，你總是可以將其描述為對法律的修復，而不是完全重新佈線[法律]。

Our probably biggest concern and focus there going to be watching from a policy standpoint is if you think of it under the IR Medicare Part D was focal in this new regime, you've got to figure that Medicaid is going to be focal just giving the amount of millipede there. So we want to make sure that in the event that Medicaid is being reconsidered or revamped that our patients, those with serious mental illness and addiction are not disadvantaged. And we think there's a good chance of doing that given the public health.

從政策角度來看，我們可能最大的擔憂和關注點是，如果您認為在 IR Medicare Part D 下，這是這一新制度的焦點，那麼您必須明白，鑑於那裡的千足蟲數量，醫療補助將成為焦點。因此，我們希望確保，如果重新考慮或修改醫療補助計劃，我們的患者、患有嚴重精神疾病和藥物成癮的患者不會受到不利影響。我們認為，考慮到公眾健康因素，這樣做很有可能。

As always, thanks for the thoughtful responses.

一如既往，感謝您深思熟慮的回覆。

Marc Goodman, Leering Partners.

馬克古德曼（Marc Goodman），Leering Partners。

Yeah, can you give us any more color on what's going on with these next-gen erections or when are you going to give us more color on what indications or just anything that you're willing to share just incrementally since we're on a live call here?

是的，您能否向我們詳細介紹一下下一代勃起的情況，或者您什麼時候會向我們詳細介紹哪些適應症，或者您願意逐步分享的任何信息，因為我們在這裡進行現場通話？

And then just secondly, I know I've asked you about business development quite often, and obviously, we're spending a great deal of money on orexins and everyone is excited about it, you should be spending the money. They're just curious what's going on behind the scenes and business development? And if -- should we be surprised if there's a deal or not a deal for anything else this year to kind of add to the pipeline? Thanks.

其次，我知道我經常問你關於業務發展的問題，顯然，我們在 Orexins 上花了很多錢，每個人都對此感到興奮，你應該花這些錢。他們只是好奇幕後發生了什麼以及業務發展如何？如果——如果今年有其他任何可以加入管道的交易，我們是否應該感到驚訝？謝謝。

Mark, I'd love to give you more information on the next generation direction not going to because I feel like our teams -- I feel like we're ahead of the curve on this. We identified the fact that we were going to go beyond narcolepsy a couple of years ago, we began a lot of investigative work of going through that panning filtration to figure out where we think the smartest places are to go next. We gave you a little bit of a directional teas in the JPMorgan presentation where we showed you where we're looking categorically in ultra-orphan as well as broader indications.

馬克，我很樂意為您提供有關下一代發展方向的更多信息，因為我覺得我們的團隊——我覺得我們在這方面走在了前面。幾年前，我們就確定了要超越嗜睡症的治療目標，並開始了大量的調查工作，透過篩選和篩選找出我們認為下一步最明智的選擇。我們在摩根大通的演示中為您提供了一些方向性的指引，向您展示了我們在超孤兒藥以及更廣泛適應症方面的分類研究。

And we've mentioned that both 4510 and 7290 were the two new erections going into the clinic this year, have different pharmacologic properties that make them somewhat distinct from ALKS 2680. And we'll give you more indications where we're going precisely as we complete the SAD and MAD studies. Because those studies are the necessary prerequisite to determine whether we have a safe, well-tolerated drug that's engaging the target. From those studies, we'll go right into what we hope will be that the orexin studies where we go into patient studies in Phase Ib or IIa or we can see early on whether we have signs of signal to confirm the hypothesis.

我們提到過，4510 和 7290 是今年進入臨床的兩種新勃起藥物，它們具有不同的藥理特性，與 ALKS 2680 略有不同。當我們完成 SAD 和 MAD 研究時，我們會向您提供更多有關我們未來方向的指示。因為這些研究是確定我們是否有安全、耐受性良好且能達到目標的藥物的必要先決條件。透過這些研究，我們將直接進入我們希望的食慾素研究，我們將進入 Ib 或 IIa 期的患者研究，或者我們可以儘早看到是否有信號跡象來證實該假設。

So on the [BD] side, you can see the pipeline expanding naturally along this orexin wakefulness hypocretin pathways. And that's going to continue to enrich. There are all some degree of covariance between them. So we're always looking for clinical-stage assets that might broaden portfolio. We're going to stay an independent pure-play neuroscience company with the financial resources we have, we will expand the pipeline. There is no question about it.

因此在 [BD] 方面，您可以看到管道沿著這種食慾素覺醒下丘腦分泌素路徑自然擴展。這將會繼續豐富。它們之間都存在一定程度的協方差。因此，我們一直在尋找可能擴大投資組合的臨床階段資產。我們將繼續作為一家獨立的純神經科學公司，利用我們擁有的財務資源擴大產品線。毫無疑問。

But we kiss a lot of frogs in the [BD] side, and we do a lot of analysis. And it's an exception rather than the rule when they get through the filter. So it's hard to predict when that and they might happen. Also, on the commercial side, you've heard us talk about before, we would love to be able to and leverage this commercial infrastructure.

但我們在 [BD] 方面親吻了很多青蛙，並且做了很多分析。當他們通過過濾器時，這是一個例外，而不是規則。因此很難預測這些事情何時發生以及會發生。此外，在商業方面，您之前已經聽我們談論過，我們很樂意能夠利用這種商業基礎設施。

And there's just not a whole lot of products, but we're always investigating ones that are emerging or nearing commercialization as well as those in the market. So I don't feel like we have a gun to our head and urgency, but we've got the financial resources and the instinct to do it.

雖然產品數量不多，但我們一直在研究新興產品、即將商業化的產品以及現有的產品。因此，我不覺得我們被逼著採取行動，也不覺得我們很緊迫，但我們有財力和本能去做到這一點。

Thank you.

謝謝。

Uy Ear, Mizuho Securities.

Uy Ear，瑞穗證券。

You guys, yeah, thanks for taking your question. Rich, maybe just a follow-up on your brief comment about Medicaid funding. Maybe just help us understand what the sources for VIVITROL is these days, given the shift from opioid to alcohol dependents.

是的，感謝你們提出問題。Rich，也許只是對你關於醫療補助資金的簡短評論的後續跟進。考慮到從鴉片類藥物依賴到酒精依賴的轉變，也許可以幫助我們了解現在 VIVITROL 的來源是什麼。

And maybe just help us kind of think about if there is in Medicaid cut. How should we sort of think about the potential risk to this product? And along that line, maybe just also help us understand the impact, I guess, from IRA Medicare Part D redesigned for this year and potentially next year? Thanks.

也許可以幫助我們思考是否可以削減醫療補助。我們該如何看待該產品的潛在風險？沿著這個思路，我想也許還能幫助我們了解今年以及明年重新設計的 IRA Medicare Part D 的影響？謝謝。

I'll take some of it. Blair, Todd, feel free to chime in. So Medicaid is an important source of business for all of our products, LYBALVI, VIVITROL, and ARISTADA. But I don't want anybody to panicky about this yet. This is all very notional. My overarch your comments on that, if you -- if one is ambitious to cut $1 trillion from the federal government, at some point, you're going to be looking at allocation of [monies to States] under Medicaid.

我會拿一些。布萊爾、托德，請隨意發表意見。因此，醫療補助是我們所有產品 LYBALVI、VIVITROL 和 ARISTADA 的重要業務來源。但我不希望任何人對此感到恐慌。這一切都只是概念性的。我對此的總體評論是，如果有人雄心勃勃地要從聯邦政府削減 1 兆美元，那麼在某個時候，你就會考慮在醫療補助計劃下[向各州分配資金]。

Now schizophrenia drugs, bipolar drugs, and addition drugs are not breaking the bank for -- in Medicaid. There's a lot of other places in Medicaid where you can look to save money. So our -- to the extent that you do see some type of Medicaid reforms, count on the fact that we will be in there advocating to maintain access to these types of medicines for patients. They're priced fairly, the gross-to-nets are high. We are responsible participants in the overall ecosystem. We're not the bad actors -- not imply is a really bad actor to say we're not the big economic swimming factor that's going to drive this.

現在，精神分裂症藥物、躁鬱症藥物和成癮藥物並不會佔用醫療補助的大部分資金。醫療補助計劃中還有很多其他地方可以幫助您省錢。因此，如果您看到某種類型的醫療補助改革，請相信我們將倡導保持患者獲得這些類型藥物的機會。它們的價格合理，毛利與淨利之比很高。我們是整個生態系中負責任的參與者。我們不是壞人——但這並不意味著我們真的是個壞人，因為我們不是推動這件事發生的重大經濟因素。

So I think we're going to have, to the extent that people start focusing on Medicaid. We think there's an opportunity actually to focus on the benefits that medication provide to chronic disease sufferers with addiction and serious mental illness.

所以我認為我們將會在某種程度上讓人們開始關注醫療補助。我們認為，實際上有機會關注藥物為患有成癮和嚴重精神疾病的慢性病患者帶來的益處。

On the Medicare Part D side, we qualify it for the phasing. So our exposure in 2025 is 1%. So that's a perfect example of how we use our positioning to drive policies that have protected companies like ours and we're providing medicines at fair prices into the system.

在醫療保險 D 部分方面，我們使其符合分階段實施的資格。因此我們在 2025 年的風險敞口是 1%。這是一個完美的例子，說明我們如何利用我們的定位來推動保護像我們這樣的公司的政策，並以公平的價格向系統提供藥物。

Could you also maybe talk a little bit about the sources of funding for VIVITROL?

您能否談談 VIVITROL 的資金來源？

Yeah. Absolutely, I can do that. So we look at the total mix. For VIVITROL, it's been relatively stable. About 50% is in the Medicaid channel. 45% or so is in commercial, and that's growing with our focus on alcohol dependence; it's more of a commercial patient. And the remainder is within the PHS segment.

是的。當然，我可以做到。因此我們來看看總體組合。對於 VIVITROL 來說，它一直相對穩定。大約50%是透過醫療補助管道。約有 45% 從事商業活動，隨著我們對酒精依賴性的關注，這一數字還在增長；他更像是一名商業病人。其餘部分則屬於 PHS 領域。

Thank you.

謝謝。

Troy Langford, TD Cowen.

特洛伊·蘭福德（Troy Langford），TD Cowen。

Hi everyone. Congrats on the quarter and thanks for taking our question. Just really quickly on ALKS 2680. How quickly do you think you also move into pivotal studies in NT1 or NT2 patients upon positive data this year. I guess part of the gating items the initiation of the Phase III studies? And do you think we could see a pivotal study before the end of the year?

大家好。恭喜本季取得佳績，感謝您回答我們的問題。關於 ALKS 2680 非常快。您認為今年基於積極的數據，您能多快進入 NT1 或 NT2 患者的關鍵研究。我猜其中一部分門控計畫是啟動第三階段研究嗎？您認為我們能在今年年底前看到一項關鍵的研究嗎？

Yeah, let's see how fast we finish up the Phase IIs, but I can tell you, a lot of the Phase II infrastructure build is anticipatory for Phase III. And so our hope the way we sequence this, we top line results in NT2, we schedule end of Phase II meeting with FDA. As soon as we can figure out of time based on our completion to have that meeting. Need with review division in this case, its DPP in divisional psychiatry.

是的，讓我們看看我們能多快完成第二階段，但我可以告訴你，第二階段的許多基礎建設都是為了第三階段做準備。因此，我們希望透過這樣的排序，獲得 NT2 的最高結果，並安排與 FDA 舉行第二階段會議的結束。只要我們根據完成情況決定時間，就可以召開會議。在這種情況下，需要審查部門，即精神病學部門的 DPP。

Depending on the results, we will probably look to file for breakthrough designation in NT2. And that opens up the line for discussions about accelerated pathways to market. So we're going to be preparing to start Phase III as quickly as we can after we complete that in a Phase II meeting with FDA.

根據結果，我們可能會考慮在 NT2 中申請突破性專利。這為加速市場途徑的討論打開了大門。因此，在與 FDA 進行第二階段會議後，我們將準備盡快啟動第三階段。

Great, thanks for the additional color.

太好了，謝謝添加顏色。

Douglas Tso, H. C. Wainright.

道格拉斯‧佐 (Douglas Tso)、H. C. 溫賴特 (H. C. Wainright)。

Hi, good morning. Thanks for taking the questions. Maybe as a starting point, Rich, I think it would be helpful to just provide some perspective on what you think your competitive advantages are in the recon space Obviously, you have a head start in terms of clinical development across some indications, and it indicates that in future broader ones outside of to sort of wait for the sleep category, you're ahead.

嗨，早安。感謝您回答這些問題。也許作為一個起點，Rich，我認為提供一些關於你認為你在偵察領域的競爭優勢的觀點會有所幫助，顯然，你在某些適應症的臨床開發方面已經領先一步，這表明在未來除了等待睡眠類別之外的更廣泛的領域，你都處於領先地位。

But maybe just from a chemistry standpoint, just because obviously, we started to see other companies begin to focus on the erection space. Maybe just walk through some of the challenges that others might experience and why you think that your sort of first-mover advantage will prove to be durable? And then I have a follow-up on the LYBALVI. Thanks.

但也許只是從化學的角度來看，因為很明顯，我們開始看到其他公司開始關注勃起空間。也許只是介紹一下其他人可能會遇到的一些挑戰，以及為什麼您認為自己的先發優勢將被證明是持久的？然後我對 LYBALVI 進行跟進。謝謝。

Hey Doug, good morning. [Oxerin] 2 receptors are broking couple receptors located in the brain. And so from a municipal chemistry perspective, it's a high degree of difficulty challenge because you need to create a small molecule GPCR agonists, which requires a fair amount of structure generally, they need to be orally bioavailable. They need to cross the wording barrier.

嘿，道格，早安。 [Oxerin] 2 受體是位於大腦的斷裂偶聯受體。因此，從市政化學的角度來看，這是一個高難度的挑戰，因為您需要創建小分子 GPCR 激動劑，這通常需要相當多的結構，它們需要具有口服生物利用度。他們需要跨越措辭障礙。

They need not to be a pump substrate, so they get bumped out of the brain. And then all that has to happen with a pharmacokinetic profile that's consistent with the natural sleep wake cycle. To enable once-a-day dosing. So we know the specific amino acid residues one needs to bind in order to have agonists. We'll publish on the data on our patents so that people will see it in more and more.

它們不需要成為泵底物，因此它們會被撞出大腦。然後，所有這一切都必須透過與自然睡眠覺醒週期一致的藥物動力學特徵來實現。實現每日一次的給藥。因此我們知道需要結合哪些特定的胺基酸殘基才能產生激動劑。我們將發布有關我們專利的數據，以便人們越來越多地看到它。

So the question is if you're coming behind us, how do you actually improve on what we and others are doing? In other words, if we have once a day dosing with a range of doses that are well tolerated that are used in NT1 and NT2 and IH? There's not a lot of space there. Now no drug is ever perfect, right? So until we fully elaborate the characteristics of this drug in the Phase II study, it remains at radical. But right now, we're quite pleased with the profile that we have.

所以問題是，如果你落後於我們，你實際上如何改進我們和其他人所做的事情？換句話說，如果我們每天服用一次用於 NT1、NT2 和 IH 的一系列耐受性良好的劑量會怎麼樣？那裡沒有太多空間。現在沒有一種藥物是完美的，對嗎？因此，在我們在第二階段研究中充分闡述這種藥物的特性之前，它仍然處於激進階段。但現在，我們對現有的狀況非常滿意。

So I think our competitive advantage right now in the current course rate is that we have positive data in all three differential diagnosis, NT1, NT2, IH. We have a range of doses, therefore, showing dose response and dose proportionality and the dosing between NT1, NT2, and IH are adjacent. That is 4 6, 8 milligrams being tested in Phase II for NT1 [then a plots] immediately against 10, 14, and 18 milligrams in NT2 and IH.

因此，我認為我們目前在目前病程率方面的競爭優勢在於我們在 NT1、NT2、IH 這三種鑑別診斷中都有正面的數據。我們有一系列劑量，因此顯示劑量反應和劑量比例，並且 NT1、NT2 和 IH 之間的劑量是相鄰的。也就是說，在第二階段針對 NT1 進行測試的劑量為 4、6、8 毫克（然後是 a 圖），而針對 NT2 和 IH 進行測試的劑量為 10、14 和 18 毫克。

So if that turns out to be somewhere close to the ultimate commercial range, it allows those patients and doctors to flexibly adjust their dose to accommodate their own individual disease needs and/or aspirational -- life aspirations as well. So I think that we like the position right now. And we also believe that as the field gets more extensively elaborated, others will come in.

因此，如果結果接近最終的商業範圍，那麼這些患者和醫生就可以靈活地調整劑量，以適應他們自己的疾病需求和/或願望——生活願望。所以我認為我們現在喜歡這個職位。我們也相信，隨著該領域的進一步發展，其他人也會加入。

And if I feel like narcolepsy is going to be well taken care of if ours and other drugs meet their profile, iSo then the action becomes the other adjacencies, which we think are quite promising. That's why we're putting 4510s and 7290s into the clinic because we want to be ahead of that as well. So we're already anticipating success in narcolepsy, recognizing the risk that still exists. But operationally, preparing now for narcolepsy from a commercial perspective, and expanding into new indications to capitalizing on the increasingly credential pharmacology.

如果我覺得我們的藥物和其他藥物符合其特性，那麼嗜睡症就能得到很好的治療，那麼行動就會變成其他鄰接領域，我們認為這些領域非常有前景。這就是我們將 4510 和 7290 投入臨床的原因，因為我們也想在這方面取得領先。因此，我們已經預見到治療嗜睡症的成功，同時也認識到仍然存在的風險。但在營運上，現在要從商業角度為嗜睡症做好準備，並擴展到新的適應症，以利用日益認證的藥理學。

And Richard, I can, a follow-up in terms of your earlier comments. So in terms of sort of the multiple characteristics that are needed or sort of boxes you need to check in the recon space, you would be sort of cautious when you look at some companies that are purporting to have sort of preclinical data or in vitro assays highlighting the sort of potency of their molecules relative to what you indicated have done just given the sort of need to -- there are the challenges around PK and penetration into the brand. Is that fair?

理查德，我可以跟進您之前的評論。因此，就所需的多種特性或需要在偵察領域檢查的框而言，當您看到一些公司聲稱擁有某種臨床前數據或體外試驗，強調其分子相對於您所指出的已經完成的效力時，您會感到謹慎——存在 PK 和品牌滲透方面的挑戰。這樣公平嗎？

I think that's fair. I think I consider potency and selectivity to be [seen in recon]. I mean you have to have high potency and high selectivity to play. But a little bit like saying I have a great race car because it has great tires you got to have an engine too, and you have some doors and some seatbelts and a helmet and all the other things and they can do a race car. So I think that all of those features, any one of those features, the deficiency handling and one of those features is going to lead to some type of competitive disadvantage.

我認為這是公平的。我認為效力和選擇性是[偵察中看到]。我的意思是你必須具有很強的效力和選擇性才能玩。但有點像說我有一輛很棒的賽車，因為它有很棒的輪胎，你還得有一個引擎，還有一些車門、一些安全帶、一個頭盔和所有其他的東西，它們就可以成為一輛賽車。所以我認為所有這些功能、其中任何一個功能、缺陷處理和其中一個功能都會導致某種競爭劣勢。

Okay great. Thank you so much.

好的，太好了。太感謝了。

The only comment I'd add to that is that in our experience, nothing really matters until you get into patients because healthy volunteers, we found in our hands that even sleep-deprived healthy volunteers do not recapitulate the sleep pressure of an NT1 patient, for example. So dosing is going to be indication-specific. And along with that is tolerability because what you find is that healthy volunteers tolerate different doses than in Q1 patients. And so our view is always, until you get into patients, you really can't get a sense of where you are with respect to therapeutic index, tolerability, safety, and dose response.

我唯一想補充的是，根據我們的經驗，在接觸患者之前，沒有什麼真正重要的事情，因為我們在健康志願者身上發現，即使是睡眠不足的健康志願者也無法重現 NT1 患者的睡眠壓力。因此劑量應根據具體情況而定。除此之外還有耐受性，因為你會發現健康志願者耐受的劑量與 Q1 患者不同。因此，我們的觀點始終是，直到您進入患者體內，您才能真正了解治療指數、耐受性、安全性和劑量反應的狀況。

Okay.

好的。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi, thanks for taking the question. For VIVITROL, what are the key dynamics that impact whether you'll be able to achieve that mid-single-digit growth rate in scripts that was mentioned earlier in the call.

你好，謝謝你回答這個問題。對於 VIVITROL，哪些關鍵動態因素會影響您是否能夠實現通話中早期提到的腳本中的中個位數成長率。

Hi, Joel, this is Todd. I'll take that. Our key focus for VIVITROL is continued expansion in alcohol dependence. That's what's been -- that's what drove the brand in 2024. We actually saw demand growth for alcohol dependence of approximately 14%, which kind of helped offset some of the headwinds that we've experienced with opioid use disorder. So we really believe that the brand will continue to grow.

你好，喬爾，我是托德。我接受。我們對 VIVITROL 的重點關注是酒精依賴性的持續擴大。這就是——這就是推動品牌在 2024 年發展的動力。我們實際上看到酒精依賴的需求增加了約 14%，這在某種程度上有助於抵消我們在鴉片類藥物使用障礙方面遇到的一些阻力。因此我們確實相信該品牌將繼續發展。

I think you have to keep in mind, too, VIVITROL is a mature brand. So overall, demand will be consistent with the mature brand but we still believe that subnational dynamics within the nonretail space, such as in the VA, for example, will continue to drive growth. So our two strategic areas are really the alcohol dependence indication subnationally, making sure that we can continue to drive access and growth within the VA.

我認為您也必須記住，VIVITROL 是一個成熟的品牌。因此總體而言，需求將與成熟品牌保持一致，但我們仍然相信，非零售領域內（例如 VA）的次國家動態將繼續推動成長。因此，我們的兩個策略領域實際上是全國範圍內的酒精依賴指徵，確保我們能夠繼續推動 VA 內的獲取和成長。

Thank you.

謝謝。

We have time for one more question.

我們還有時間再回答一個問題。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

Hi, everyone. Thank you for taking my question. This is Alex on for David. Just one question for me. I know you touched earlier on competitive impacts associated with LYBALVI and why don't you dive more into that. [COVENFI] is developing a long-acting injectable form of olanzapine. I believe that they're submitting an NDA later this year, how would that impact the LYBALVI business?

大家好。感謝您回答我的問題。這是亞歷克斯 (Alex) 為戴維 (David) 主持的節目。我只想問一個問題。我知道您之前談過 LYBALVI 對競爭的影響，為什麼不深入探討這個問題呢？ [COVENFI] 正在開發一種長效注射劑型奧氮平。我相信他們將在今年稍後提交一份保密協議，這會對 LYBALVI 業務產生什麼影響？

And are you anticipating that as any sort of headwind Also, have you seen any impact from [COVENFI] yet? Or do you anticipate any -- as that product continues to ramp? Thank you.

您是否預期這會帶來任何不利因素？另外，您是否已經看到 [COVENFI] 的影響？或者您是否預期—隨著該產品的持續成長？謝謝。

Sure. Yes, this is Todd. I'll take the last one first. So at this point, we haven't seen any impact to LYBALVI with [COVENFI]. In Q4, we saw TRx growth of 5% overall, which is very consistent with Q3, and we expect strong demand growth throughout 2025. I think it's just really important to remember with LYBALVI, it's a broad indication, so bipolar disorder and schizophrenia versus [COVENFI] just in schizophrenia.

當然。是的，這是托德。我先拿最後一個。因此目前我們還沒有看到 LYBALVI 受到任何影響[科文菲]。在第四季度，我們看到 TRx 整體成長了 5%，這與第三季度非常一致，我們預計 2025 年全年需求都會強勁成長。我認為，真正需要記住的是，LYBALVI 的適應症很廣泛，因此可以用於治療躁鬱症和精神分裂症，而 [COVENFI] 僅適用於精神分裂症。

And we're actually -- in Q4, we saw a robust volume growth with both of those indications. In fact, we saw approximately 20% volume growth in the bipolar disorder indication. So it's a broad indication, broad population, and we feel really confident with our plan for '25, which has really underpinned with the expansion of the sales force.

事實上，在第四季度，我們看到了這兩個指標的強勁銷售成長。事實上，我們看到雙極性情感障礙的治療量增加了約 20%。因此，這是一個廣泛的跡象，廣泛的人群，我們對我們的'25計劃非常有信心，它確實為銷售隊伍的擴張奠定了基礎。

In terms of the potential olanzapine LAI. That's obviously something we always watch competitive dynamics. And we have a really strong capability with the olanzapine molecule. It's something that we know really well.

就潛在的奧氮平 LAI 而言。這顯然是我們一直在關注的競爭動態。我們對奧氮平分子具有非常強的能力。這是我們非常了解的事情。

And I think, really, the way that I would think about this is historically, and it hasn't changed, the rate limiting factor regardless of delivery for olanzapine molecule is really around weight gain and also around metabolics. That's the whole reason why we develop LYBALVI. So LYBALVI, we believe, will continue to show strong growth even in the face of any additional competition.

我認為，實際上，我對此的看法是從歷史上看的，而且它沒有改變，無論奧氮平分子如何輸送，其限速因素實際上都與體重增加和代謝有關。這就是我們開發 LYBALVI 的全部原因。因此，我們相信，即使面臨任何額外的競爭，LYBALVI 仍將繼續保持強勁成長。

The only thing I add that all typically, an LAI interest doesn't affect your oral side of the market. The LAI is its own sort of rarefied aspect. We wish it were a bigger part of the treatment algorithm, but it's relatively small. And LYBALVI obviously operates in that oral category, which is the vast majority of prescriptions.

我唯一要補充的是，通常情況下，LAI 利益不會影響您的口頭市場。LAI 本身就是一種稀薄的現象。我們希望它成為治療演算法中更重要的一部分，但它相對較小。LYBALVI 顯然屬於口服藥物類別，而該類別佔處方藥的絕大多數。

All right, everyone. Thanks for joining us on the call this morning. If there are any follow-up questions, please don't hesitate to reach out to us at the company.

好的，各位。感謝您參加今天早上的電話會議。如果有任何後續問題，請隨時與我們公司聯繫。

Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.

謝謝。今天的電話會議到此結束。現在您可以斷開您的線路。感謝您的參與。