Alkermes Plc (ALKS) 2023 Q2 法說會逐字稿

Greetings, and welcome to the Alkermes Second Quarter 2023 Earnings Financial Results Conference Call. My name is Marianne, I'll be your operator for today's call. (Operator Instructions) Please note that this conference is being recorded. I'll now turn the call over to Sandra Coombs, Senior Vice President of Investor Relations and Corporate Affairs. Sandy, you may begin.

您好，歡迎參加 Alkermes 2023 年第二季度收益財務業績電話會議。我叫瑪麗安，我是今天電話的接線員。 （操作員說明）請注意，本次會議正在錄製中。我現在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)。桑迪，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 ended June 30, 2023. With me today are Richard Pops, our CEO; Iain Brown, our CFO; and Todd Nichols, our Chief Commercial Officer. Before we begin, I encourage everyone to go to the Investors section of alkermes.com to find our press release, related financial tables and reconciliations of the GAAP to non-GAAP financial measures that we'll discuss today. We believe the non-GAAP financial results in conjunction with the GAAP results are useful in understanding the ongoing economics of our business.

謝謝。早上好。歡迎參加 Alkermes plc 電話會議，討論我們截至 2023 年 6 月 30 日的季度的財務業績和業務更新。今天與我在一起的是我們的首席執行官 Richard Pops；伊恩·布朗，我們的首席財務官；和我們的首席商務官托德·尼科爾斯。在開始之前，我鼓勵大家訪問 alkermes.com 的投資者部分，查找我們今天將討論的新聞稿、相關財務表格以及 GAAP 與非 GAAP 財務指標的調節表。我們相信，非公認會計準則財務業績與公認會計準則業績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 and quarterly reports 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. 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. And now I'll turn the call over to Iain.

我們在本次電話會議期間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存在重大差異。請參閱隨附演示文稿的幻燈片2、我們今天上午發布的新聞稿以及我們向SEC 提交的最新年度和季度報告，了解可能導致我們的實際結果與前瞻性陳述中明示或暗示的結果存在重大差異的重要風險因素。聲明。我們不承擔因新信息或未來結果或發展而更新或修改本次電話會議或隨附演示文稿中提供的信息的義務。在我們準備好的發言之後，我們將開始問答環節。現在我將把電話轉給伊恩。

Great. Thank you, Sandy, and hello, everyone. Our second quarter results reflect strong execution across our business, highlighted by the 21% year-over-year growth of our 3 proprietary commercial products and reinstatement of the long-acting INVEGA royalties in the U.S. following our success in the arbitration with Janssen, which concluded during the quarter.

偉大的。謝謝你，桑迪，大家好。我們第二季度的業績反映了我們整個業務的強勁執行力，其中最突出的是我們的3 種專有商業產品同比增長21%，以及在我們與楊森(Janssen) 仲裁成功後恢復了美國的長期INVEGA 特許權使用費。本季度結束。

This clear resolution further enhances our financial strength and is complemented by our progress in separating the oncology business, our ongoing emphasis on operating efficiency and our commitment to profitability as reflected in our 2024 and 2025 profitability targets. Before reviewing the underlying business results for the quarter, I'll walk through the impact of the final award from the Janssen arbitration as it relates to our second quarter financial results as there are a number of important elements.

這一明確的決議進一步增強了我們的財務實力，並輔以我們在分離腫瘤業務方面取得的進展、我們對運營效率的持續重視以及我們對盈利能力的承諾，這反映在我們的2024 年和2025年盈利目標中。在審查本季度的基本業務業績之前，我將介紹一下詹森仲裁最終裁決的影響，因為它與我們第二季度的財務業績相關，因為有許多重要因素。

First, we recorded $197.1 million of back royalties and associated interest related to 2022 as revenue in the quarter. Of this, $195.4 million related to the long-acting INVEGA products and $1.7 million to Cabenuva. This revenue is reflected in our GAAP results. However, it is excluded from our Q2 non-GAAP net income.

首先，我們將 1.971 億美元的特許權使用費和與 2022 年相關的相關利息記錄為本季度的收入。其中，1.954 億美元與長效 INVEGA 產品相關，170 萬美元與 Cabenuva 相關。該收入反映在我們的 GAAP 業績中。然而，它不包括在我們第二季度非公認會計準則淨利潤中。

Second, we recorded $51.3 million of incremental royalty revenue related to Q1 2023, of which $50.2 million related to the long-acting INVEGA products and $1.1 million to Cabenuva. In total, we have received $248.4 million of back royalties and interest from Janssen and these proceeds are reflected in our cash position at the end of the second quarter.

其次，我們記錄了與 2023 年第一季度相關的 5130 萬美元增量特許權使用費收入，其中 5020 萬美元與長效 INVEGA 產品相關，110 萬美元與 Cabenuva 相關。我們總共從楊森收到了 2.484 億美元的返還特許權使用費和利息，這些收益反映在我們第二季度末的現金狀況中。

And last, we recorded $76.9 million of royalties on Q2 worldwide net sales of these products, of which $75.7 million related to the long-acting INVEGA products and $1.3 million related to Cabenuva. Royalty revenues related to Q1 and Q2 of 2023 are reflected in both our GAAP and non-GAAP net income in the second quarter. All told, we recognized $325.3 million of royalties and interest in the second quarter related to these products, all of which was included in GAAP net income, while $128.3 million related to 2023 net sales was included in non-GAAP net income.

最後，我們記錄了這些產品第二季度全球淨銷售額的 7690 萬美元特許權使用費，其中 7570 萬美元與長效 INVEGA 產品相關，130 萬美元與 Cabenuva 相關。與 2023 年第一季度和第二季度相關的特許權使用費收入反映在我們第二季度的 GAAP 和非 GAAP 淨利潤中。總而言之，我們在第二季度確認了與這些產品相關的3.253 億美元的特許權使用費和利息，所有這些都包含在GAAP 淨利潤中，而與2023 年淨銷售額相關的1.283 億美元包含在非GAAP 淨利潤中。

So now turning to our full Q2 financial results. For the second quarter, we recorded total revenues of $617.4 million, which included robust performance across our proprietary product portfolio, which grew 21% year-over-year. Starting with VIVITROL. Net sales in the quarter were $102.1 million, reflecting 6% growth year-over-year, driven primarily by growth in the alcohol dependence indication. Inventory in the channel was stable and gross to net deductions were within normal ranges for the quarter.

現在轉向我們第二季度的完整財務業績。第二季度，我們的總收入為 6.174 億美元，其中包括我們專有產品組合的強勁表現，同比增長 21%。從 VIVITROL 開始。該季度淨銷售額為 1.021 億美元，同比增長 6%，這主要是由酒精依賴指標的增長推動的。該渠道庫存穩定，本季度毛淨扣除額處於正常範圍內。

For the full year, we continue to expect VIVITROL net sales in the range of $380 million to $410 million with demand expected to be fairly stable over each of the next 2 quarters. Moving on to the ARISTADA product family. For the quarter, ARISTADA net sales increased 10% year-over-year to $82.4 million, driven primarily by higher underlying demand. Inventory in the channel was stable and gross to net deductions were within normal ranges for the quarter. And for the full year, we continue to expect ARISTADA net sales in the range of $315 million to $345 million.

我們繼續預計 VIVITROL 全年淨銷售額在 3.8 億美元至 4.1 億美元之間，預計未來兩個季度的需求將相當穩定。繼續討論 ARISADA 產品系列。本季度，ARISADA 淨銷售額同比增長 10% 至 8,240 萬美元，這主要是由於潛在需求增加所致。該渠道庫存穩定，本季度毛淨扣除額處於正常範圍內。我們繼續預計 ARISADA 全年淨銷售額將在 3.15 億美元至 3.45 億美元之間。

LYBALVI net sales for the quarter were $47 million, up 24% sequentially. Underlying prescription growth was 16% and during the quarter, inventory in the channel rebounded to normal levels following relatively lower levels at the end of the first quarter. Gross to net adjustments in Q2 were approximately 26%, reflecting a continuation of our disciplined contracting strategy in the commercial space. We currently expect that gross to net adjustments will remain fairly stable for the remainder of 2023. For the full year, we expect LYBALVI net sales will be towards the higher end of our previously provided guidance range of $180 million to $205 million.

LYBALVI 本季度淨銷售額為 4700 萬美元，比上一季度增長 24%。基本處方增長率為 16%，本季度渠道庫存繼第一季度末相對較低水平後反彈至正常水平。第二季度的毛淨調整約為 26%，反映出我們在商業領域繼續實施嚴格的承包戰略。我們目前預計 2023 年剩餘時間內毛淨調整將保持相當穩定。全年，我們預計 LYBALVI 淨銷售額將接近我們之前提供的指導範圍 1.8 億至 2.05 億美元的上限。

Moving on to our manufacturing and royalty business, in addition to the Janssen royalties I've already discussed, the company recorded revenues from VUMERITY of $32.3 million compared to $26.2 million in the same period in the prior year.

繼續我們的製造和特許權使用費業務，除了我已經討論過的楊森特許權使用費外，該公司從 VUMERITY 獲得的收入為 3230 萬美元，而去年同期為 2620 萬美元。

Turning to expenses. Total operating expenses were $378.2 million for the second quarter compared to $310.7 million in the same period in the prior year. R&D expenses for the second quarter were $100.8 million compared to $92.9 million for the same period in the prior year, reflecting acceleration in recruitment of the ongoing nemvaleukin clinical studies, advancement of our ALKS 2680, Orexin 2 receptor agonist program into Phase Ib and ongoing LYBALVI lifecycle management studies.

轉向開支。第二季度總運營費用為 3.782 億美元，上年同期為 3.107 億美元。第二季度的研發費用為1.008 億美元，而上年同期為9290 萬美元，反映出正在進行的Nemvaleukin 臨床研究的招募加速、我們的ALKS 2680、Orexin 2 受體激動劑項目進入Ib 期以及正在進行的LYBALVI生命週期管理研究。

SG&A expenses increased to $205.3 million from $150.4 million for the same period in the prior year. The increase was largely driven by a $28 million investment in the LYBALVI direct-to-consumer campaign, including the start of the TV component in May as well as certain expenses related to the separation of the oncology business. Looking ahead, we currently expect DTC related expenses to be lower in each of the next 2 quarters. Our top line results, combined with our continued focus on disciplined operating expense management, resulted in a GAAP net income of $237.1 million and non-GAAP net income of $94.3 million for the quarter, which, as I mentioned, excludes the Janssen back royalties and associated interest of $197.1 million related to 2022.

SG&A 費用從上年同期的 1.504 億美元增至 2.053 億美元。這一增長主要是由於對 LYBALVI 直接面向消費者活動的 2800 萬美元投資推動的，包括 5 月份電視部分的啟動以及與腫瘤業務分離相關的某些費用。展望未來，我們目前預計未來 2 個季度的 DTC 相關費用將會降低。我們的頂線業績，加上我們對嚴格運營費用管理的持續關注，導致本季度GAAP 淨利潤為2.371 億美元，非GAAP 淨利潤為9,430 萬美元，正如我提到的，其中不包括楊森返還特許權使用費和與 2022 年相關的相關利息為 1.971 億美元。

Turning to our balance sheet, we are in a strong financial position as we ended the second quarter with $907.2 million in cash and total investments, with total debt outstanding of $292 million. This positions us well to appropriately capitalize mural oncology upon separation, which we continue to expect will be in the order of $200 million to $300 million. Today, we are reiterating our financial expectations for 2023 that we previously raised on June 6, following the successful outcome in the Janssen arbitration.

談到我們的資產負債表，我們的財務狀況強勁，第二季度末我們的現金和總投資為 9.072 億美元，未償債務總額為 2.92 億美元。這使我們能夠在分離後適當地利用壁畫腫瘤學，我們仍然預計該資本額將達到 2 億至 3 億美元。今天，在楊森仲裁案取得成功之後，我們重申我們之前於 6 月 6 日提出的 2023 年財務預期。

As a reminder, our financial expectations reflect the combined neuroscience and oncology business for the full year. We remain on track to complete the separation in the second half of the year. So in conclusion, as we enter the second half of the year, we are well positioned financially to execute on our strategic priorities: drive the launch of LYBALVI, advance the ALKS 2680 clinical program and complete the separation of the oncology business. We will continue to focus on driving strong performance and momentum across the business to create long-term value for our shareholders. And with that, I'll hand the call over to Todd.

提醒一下，我們的財務預期反映了全年神經科學和腫瘤學業務的綜合情況。我們仍有望在今年下半年完成分離。總而言之，隨著進入下半年，我們在財務上處於有利地位，可以執行我們的戰略重點：推動 LYBALVI 的上市，推進 ALKS 2680 臨床項目並完成腫瘤業務的分離。我們將繼續專注於推動整個業務的強勁業績和勢頭，為股東創造長期價值。接下來，我會將電話轉交給托德。

Thank you, Iain, and good morning, everyone. I am pleased to share that we delivered solid growth across our proprietary commercial portfolio again in the second quarter with 21% year-over-year growth. Our sales performance during the quarter was driven by strong execution by our commercial organization. We are particularly pleased with the continued uptake of LYBALVI in the oral antipsychotic market. So let's start there.

謝謝你，伊恩，大家早上好。我很高興地告訴大家，我們的專有商業產品組合在第二季度再次實現了穩健增長，同比增長 21%。我們本季度的銷售業績得益於我們商業組織的強大執行力。我們對 LYBALVI 在口服抗精神病藥市場的持續採用感到特別高興。那麼讓我們從這裡開始吧。

During the quarter, LYBALVI net sales were $47 million. Prescriptions grew 16% sequentially to approximately 38,300 TRxs for the second quarter. Importantly, growth of new-to-brand prescriptions accelerated sequentially as well. As we outlined earlier this year, our strategy for LYBALVI in 2023 is focused on 3 key initiatives: grow prescriber breadth, optimize our access profile and build awareness for LYBALVI. During the quarter, prescriber breadth grew by 1,800 prescribers to approximately 11,150 health care providers who had written a prescription since launch.

本季度，LYBALVI 淨銷售額為 4700 萬美元。第二季度處方藥數量環比增長 16%，達到約 38,300 份 TRx。重要的是，新品牌處方的增長也連續加速。正如我們今年早些時候概述的那樣，我們 2023 年 LYBALVI 的戰略重點關注 3 個關鍵舉措：擴大處方者範圍、優化我們的准入資料以及提高 LYBALVI 的知名度。本季度，自推出以來開過處方的處方者數量增加了 1,800 名，達到約 11,150 名醫療保健提供者。

In our recent market research, health care providers cited LYBALVI's efficacy, weight gain profile and patient outcomes as key drivers for their increased prescribing, which is encouraging feedback as we think about brand awareness and potential future prescribing patterns. And LYBALVI persistency continue to be in line with other branded oral atypical antipsychotics and better than generic olanzapine as we expected. Market access continues to play an important role for LYBALVI, like all brands in this space. In Medicare and Medicaid, we currently have a pathway to access for all patients.

在我們最近的市場研究中，醫療保健提供者將LYBALVI 的功效、體重增加情況和患者結果列為增加處方的關鍵驅動因素，當我們考慮品牌知名度和未來潛在的處方模式時，這是令人鼓舞的反饋。 LYBALVI 的持久性繼續與其他品牌口服非典型抗精神病藥物一致，並且比我們預期的仿製藥奧氮平更好。與該領域的所有品牌一樣，市場准入對 LYBALVI 繼續發揮著重要作用。在醫療保險和醫療補助方面，我們目前為所有患者提供了獲取途徑。

On the commercial side, we are pleased with how our commercial access strategy is playing out. We made deliberate decisions to focus on maximizing net revenues and limit commercial contracting at this stage of the launch. From a net sales perspective, we believe that maintaining a higher average selling price in the commercial channel outweighs any access limitations we have encountered as a result thus far. Going forward, we will continue to evaluate our contracting strategy in the commercial space, balancing volume growth and the profitability of each unit.

在商業方面，我們對商業准入策略的實施情況感到滿意。我們深思熟慮地決定在發布的這個階段專注於淨收入最大化並限製商業合同。從淨銷售額的角度來看，我們認為在商業渠道中保持較高的平均售價勝過我們迄今為止遇到的任何准入限制。展望未來，我們將繼續評估我們在商業領域的承包策略，平衡銷量增長和每個單位的盈利能力。

With that said, we expect LYBALVI's commercial access profile to remain fairly stable for at least the remainder of 2023. Our DTC campaign will be a key factor in driving awareness and maximizing the opportunity for LYBALVI in the long term. The TV component of our DTC program launched during the first week of May and is focused on bipolar 1 disorder. The campaign is designed to drive high levels of awareness amongst patients, caregivers and health care providers.

話雖如此，我們預計 LYBALVI 的商業准入狀況至少在 2023 年剩餘時間裡將保持相當穩定。從長遠來看，我們的 DTC 活動將是提高意識並最大限度地增加 LYBALVI 機會的關鍵因素。我們的 DTC 計劃的電視部分於 5 月第一周推出，重點關注雙相情感障礙 1。該活動旨在提高患者、護理人員和醫療保健提供者的認識。

We will pulse our investments in broadcast advertising based on expected ROI with greater investment and ad placement when broadcast TV viewership is highest in the spring finale and fall premier seasons. While it will take some time to see the full impact, leading indicators on the effectiveness of the DTC campaign have been encouraging. We will -- we continue to believe LYBALVI is on a strong growth trajectory and look forward to sharing our progress with you.

當春季大結局和秋季首播季廣播電視收視率最高時，我們將根據預期投資回報率調整廣播廣告投資，並加大投資和廣告投放。雖然需要一段時間才能看到全面影響，但 DTC 活動有效性的領先指標令人鼓舞。我們仍然相信 LYBALVI 正處於強勁的增長軌道，並期待與您分享我們的進展。

Turning to the ARISTADA product family. Net sales in the second quarter grew 10% year-over-year to $82.4 million, driven primarily by TRx growth of approximately 5.4% on a month of therapy basis. We are encouraged to see continued sequential growth in ARISTADA new-to-brand prescriptions, which we believe was driven by strong share of voice in the long-acting atypical market. We expect this market will continue to be dynamic and our team will continue to focus on highlighting ARISTADA's differentiated value proposition, including its every 2-month dosing option in the ARISTADA INITIO initiation regimen, both of which are supported by clinical data from our ALPINE study.

轉向 ARISADA 產品系列。第二季度的淨銷售額同比增長 10%，達到 8240 萬美元，這主要是由於 TRx 按治療月份計算增長約 5.4%。我們很高興看到 ARISADA 新品牌處方藥的持續連續增長，我們認為這是由長效非典型市場的強大話語權推動的。我們預計這個市場將繼續充滿活力，我們的團隊將繼續專注於強調ARISADA 的差異化價值主張，包括ARISADA INITIO 起始方案中每2 個月一次的給藥選項，這兩者都得到了我們ALPINE 研究的臨床數據的支持。

Turning to VIVITROL. Net sales in the second quarter increased approximately 6% year-over-year to $102.1 million. The alcohol dependence indication continued to be an important driver of growth and accounted for approximately 2/3 of the VIVITROL volume. Importantly, against the backdrop of continued growth in the alcohol dependence treatment market, prescriber breadth for VIVITROL has continued to expand within the alcohol dependence indication, which has driven new patient starts over recent quarters.

轉向 VIVITROL。第二季度淨銷售額同比增長約 6% 至 1.021 億美元。酒精依賴適應症仍然是增長的重要驅動力，約佔 VIVITROL 銷量的 2/3。重要的是，在酒精依賴治療市場持續增長的背景下，VIVITROL 的處方範圍在酒精依賴適應症中持續擴大，這推動了近幾個季度新患者的開始使用。

We also continue to see signs of stabilization for the opioid dependent side of the business, particularly within our top 5 volume states. As a reminder, the trial in our VIVITROL patent litigation with Teva took place in February, and we continue to expect a decision in the second half of this year. We remain confident in the strength of our case. However, regardless of the outcome of this litigation, we continue to believe that the nature of the product and the complexities and dynamics of the market in which it is commercialized make typical generic erosion unlikely.

我們還繼續看到阿片類藥物依賴業務穩定的跡象，特別是在銷量排名前 5 的州內。提醒一下，我們與 Teva 的 VIVITROL 專利訴訟的審判已於 2 月份進行，我們預計將在今年下半年做出裁決。我們對我們案件的實力仍然充滿信心。然而，無論該訴訟的結果如何，我們仍然認為該產品的性質以及其商業化市場的複雜性和動態性使得典型的仿製藥侵蝕不太可能發生。

Overall, we continue to be pleased with the performance of our commercial product portfolio and the strong execution of our commercial strategy by our team. We look forward to updating you on our progress as we move through the second half of 2023. And with that, I'll hand the call over to Rich.

總體而言，我們仍然對我們的商業產品組合的表現以及我們團隊對商業戰略的強有力執行感到滿意。我們期待著在 2023 年下半年向您通報我們的最新進展。接下來，我會將電話轉交給 Rich。

That's great. Thank you, Todd. The second quarter was important. We had a number of critical accomplishments that were central to our plan for the year. Strong commercial performance, success in the Janssen arbitration and reinstatement of the associated royalties, commencement of the Phase Ib study for ALKS 2680, advancement of enrollment in our oncology studies, progress toward the planned separation of the oncology business, and the successful reelection of our directors at our Annual Shareholder Meeting.

那太棒了。謝謝你，托德。第二季度很重要。我們取得了許多關鍵成就，這些成就對我們今年的計劃至關重要。強勁的商業表現、楊森仲裁案的成功以及相關特許權使用費的恢復、ALKS 2680 Ib 期研究的開始、腫瘤學研究註冊的推進、腫瘤學業務計劃分離的進展以及我們的成功連任董事出席我們的年度股東大會。

So now as we enter the second half of the year, we expect a number of important domains within the business to come more sharply into focus. The value of the commercial portfolio, including LYBALVI, initial resolution of the VIVITROL and a litigation, clinical proof-of-concept data for ALKS 2680 in narcolepsy and completion of the separation of our oncology business. Each of these elements represents an important opportunity to drive value.

因此，現在隨著進入下半年，我們預計業務中的許多重要領域將更加受到關注。商業組合的價值，包括 LYBALVI、VIVITROL 的初步解決和訴訟、ALKS 2680 治療發作性睡病的臨床概念驗證數據以及完成腫瘤業務的分離。這些要素中的每一個都代表著推動價值的重要機會。

So taking each in turn. First, the value of our commercial portfolio and the commercial organization that we've built. As you've heard from Todd and Iain, our commercial organization has continued to generate robust growth for our proprietary products, driven by an intense focus on execution of our commercial strategy.

所以依次進行。首先，我們的商業投資組合和我們建立的商業組織的價值。正如您從托德和伊恩那裡聽到的那樣，在高度重視商業戰略執行的推動下，我們的商業組織繼續為我們的專有產品帶來強勁增長。

Now in its second year of launch, LYBALVI has continued to review with potential in the large oral atypical market. The start of the broadcast DTC campaign during the quarter was a significant milestone. DTC is an essential component for every big brand in this market and we expect DTC to be an important driver of awareness and uptake of LYBALVI, building on the strong momentum we've established.

如今，LYBALVI 已進入上市第二年，繼續審視其在大型口腔非典型市場的潛力。本季度廣播 DTC 活動的啟動是一個重要的里程碑。 DTC 是該市場中每個大品牌的重要組成部分，我們預計 DTC 將在我們已建立的強勁勢頭的基礎上，成為提高 LYBALVI 認知度和接受度的重要驅動力。

Our LYBALVI strategy is designed to maximize net revenue growth and profitability over the long term and demonstrate the operating leverage we've engineered into the business. We're confident in our strategy. So our focus will continue to be on execution. Next on VIVITROL. We expect initial resolution of VIVITROL and litigation in the fall. I say initial because either party may choose to appeal the decision whichever way it goes, which would introduce a new cycle of legal interaction. For this reason, we would not expect changes in our go-to-market strategy for VIVITROL in either 2023 or 2024.

我們的 LYBALVI 戰略旨在最大限度地提高長期淨收入增長和盈利能力，並展示我們為業務設計的運營槓桿。我們對我們的戰略充滿信心。因此，我們的重點將繼續放在執行上。接下來是 VIVITROL。我們預計 VIVITROL 和訴訟的初步解決將在秋季進行。我說最初是因為任何一方都可以選擇對決定提出上訴，無論採取哪種方式，這將引入新的法律互動週期。因此，我們預計 VIVITROL 的上市策略在 2023 年或 2024 年都不會發生變化。

With that said, as Todd noted, we're confident in the innovation embodied in VIVITROL. I would not expect typical generic erosion in this market. VIVITROL is an important treatment option for opioid and alcohol dependence, and we believe it will be a key product in our portfolio for the foreseeable future.

儘管如此，正如 Todd 指出的那樣，我們對 VIVITROL 所體現的創新充滿信心。我預計這個市場不會出現典型的通用侵蝕。 VIVITROL 是阿片類藥物和酒精依賴的重要治療選擇，我們相信在可預見的未來它將成為我們產品組合中的關鍵產品。

So turning to ALKS 2680, our Orexin 2 receptor agonist program. The program is designed to generate key data early in its clinical development, and we are moving quickly. Based on the progress we made earlier this year in the single and multiple ascending dose parts of the Phase I study, in the second quarter, we initiated a Phase Ib proof-of-concept study in patients. This proof-of-concept study is evaluating established clinical efficacy endpoints, including EEG-based maintenance of wakefulness test in patients with narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia.

因此，轉向 ALKS 2680，我們的 Orexin 2 受體激動劑計劃。該計劃旨在在臨床開發的早期生成關鍵數據，我們正在迅速採取行動。基於我們今年早些時候在 I 期研究的單次和多次遞增劑量部分取得的進展，在第二季度，我們在患者中啟動了 Ib 期概念驗證研究。這項概念驗證研究正在評估已確定的臨床療效終點，包括對 1 型發作性睡病、2 型發作性睡病和特發性嗜睡症患者進行基於腦電圖的清醒維持測試。

In a crossover design, subjects will act as their own control and receive single doses of multiple dose levels as well as placebo with a washout period in between. With a small number of subjects per cohort, we believe this approach will allow us to efficiently assess initial dose response and inform dose ranges for potential future clinical studies. Enrollment in the narcolepsy type 1 patients is on track, and we continue to expect initial data from the Ib study later this year. And we look forward to sharing this data with the scientific and investor communities. In the meantime, while we enroll the Ib study, we're preparing our Phase II clinical development program. So we'll be ready to advance it as quickly as appropriate.

在交叉設計中，受試者將充當自己的對照，並接受多個劑量水平的單劑量以及安慰劑，其間有一個清除期。由於每個隊列的受試者數量較少，我們相信這種方法將使我們能夠有效評估初始劑量反應並為未來潛在的臨床研究提供劑量範圍。 1 型發作性睡病患者的入組工作正在按計劃進行，我們繼續期待今年晚些時候 Ib 研究的初步數據。我們期待與科學界和投資者界分享這些數據。與此同時，在我們招募 Ib 研究的同時，我們正在準備 II 期臨床開發計劃。因此，我們將準備好盡快推進它。

I'll finish with the separation of the Mural Oncology business. Mural Oncology will be a new independent public company. We are on track with our original time line to complete the separation in the second half of the year and have made important progress as we approach the final stages of this process. Most notably, we announced the appointment of Dr. Caroline Loew as the Chief Executive Officer designate of neuro-oncology. Dr. Loew joined us in June as a strategic adviser, and she'll transition to CEO of Mural Oncology upon completion of the separation. Dr. Loew's deep knowledge of the oncology field, extensive leadership experience and strong track record of execution and strategic business development make her uniquely qualified to lead Mural Oncology when it begins its journey as a stand-alone company.

我將結束壁畫腫瘤業務的分離。 Mural Oncology 將成為一家新的獨立上市公司。我們正按照原定時間表在今年下半年完成分離，並在接近這一過程的最後階段時取得了重要進展。最值得注意的是，我們宣布任命 Caroline Loew 博士為神經腫瘤學候任首席執行官。 Loew 博士於 6 月加入我們，擔任戰略顧問，離職完成後，她將轉任 Mural Oncology 首席執行官。 Loew 博士對腫瘤學領域的深入了解、豐富的領導經驗以及良好的執行和戰略業務發展記錄，使她在 Mural Oncology 開始作為一家獨立公司的旅程時擁有獨特的資格來領導該公司。

Now with Caroline in place, we're building out the independent members of the Murals Board and other senior members of the Mural leadership team. And I'm pleased with the caliber of the candidates that are coming through this process. The separation will provide shareholders and investors with an independent and more direct opportunity to realize value from the oncology investments that we've made. It will also reveal the value of our neuroscience business. Following the separation, Alkermes will become a pure-play profitable and growing neuroscience company. With a strong top line driven by the growth of our proprietary products, including LYBALVI, which is still early in its launch, a specialized commercial infrastructure, proven drug development capabilities and an important pipeline opportunity in ALKS 2680, we see significant opportunity to unlock value in the near future.

現在卡羅琳就位後，我們正在組建壁畫委員會的獨立成員和壁畫領導團隊的其他高級成員。我對通過這一過程的候選人的才能感到滿意。此次分離將為股東和投資者提供獨立且更直接的機會，以從我們所做的腫瘤投資中實現價值。它還將揭示我們神經科學業務的價值。分拆後，Alkermes 將成為一家盈利且不斷發展的純神經科學公司。憑藉我們的專有產品（包括仍處於上市初期的 LYBALVI）增長推動的強勁營收、專業的商業基礎設施、經過驗證的藥物開發能力以及 ALKS 2680 的重要管道機會，我們看到了釋放價值的重大機會在不遠的將來。

The coming months will be an inflection point in the evolution of the company and look forward to sharing our progress with you. So with that, I'll turn it back to Sandy to manage the Q&A.

未來幾個月將是公司發展的轉折點，期待與您分享我們的進展。因此，我會將其轉回桑迪來管理問答。

Great. Thanks, Maria, we can start the Q&A polling, please.

偉大的。謝謝瑪麗亞，我們可以開始問答投票了。

(Operator Instructions) Our first question comes from Chris Shibutani with Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的 Chris Shibutani。

Two questions, if I may. First, on the Orexin program. I think we are all anticipating in the investment community, the data that will come by year-end. I think you've highlighted NT1 is data that we would see from the Phase Ib. During the first quarter call, you did reference the importance of the different segments, potentially for different levels of potency. And also, we know that you have expertise with probably a test of tool compounds that are also available. So how should we be thinking about the Phase II program that you alluded to being able to prepare it into? What would you need to see in terms of thinking about whether you would possibly take additional doses, do more work for the other segments of NT2 and IH or bring other compounds into the clinic.

如果可以的話，有兩個問題。首先，關於食慾素計劃。我認為投資界都在期待年底公佈的數據。我認為您已經強調 NT1 是我們從 Ib 階段看到的數據。在第一季度的電話會議中，您確實提到了不同細分市場的重要性，可能具有不同的效力水平。而且，我們知道您可能擁有對現有工具化合物進行測試的專業知識。那麼，我們應該如何考慮您提到的能夠為其做好準備的第二階段計劃呢？在考慮是否可能服用額外劑量、為 NT2 和 IH 的其他部分做更多工作或將其他化合物帶入臨床時，您需要看到什麼。

Then the second question would be on profitability. You highlighted that, particularly regardless of the outcome of VIVITROL, the level of intensity and support would be the same in '23 and '24. When you talked about how the commercial complexity make it so it won't be a typical generic erosion curve. But regardless of the timing, it seems as if VIVITROL at some point may have an entrant. Should we think that the opioid segment is more protected and the alcohol is the one that's more vulnerable? And should we think that your level of spending and support would decrease when there's a competitive entrant that potentially could be at a discount?

那麼第二個問題就是盈利能力。您強調，特別是無論 VIVITROL 的結果如何，23 年和 24 年的強度和支持水平都是相同的。當您談到商業複雜性如何使其不會成為典型的通用侵蝕曲線時。但無論時間如何，VIVITROL 似乎在某個時候可能會有新的進入者。我們是否應該認為阿片類藥物更受保護，而酒精更容易受到傷害？當有可能打折的競爭者進入時，我們是否應該認為您的支出和支持水平會降低？

Chris, it's Rich. I'll try both of those, and I'll ask Todd and Iain to chime in if they need to. First on the Orexin. first of all, just to be clear, the distinction between NT1, NT2, and IH, it won't be one based on potency. The potency is inherent in the compound. And so far, work in the clinic suggests that we're very happy with where we're seeing the potency. The difference may be in dose. And that actually informs the design of the Ib study, whereas I mentioned, each patient is serving as their own control, and we're escalating doses in single dose format using the maintenance of wakefulness test and placebo to give basically a small dose response curve for each patient.

克里斯，我是里奇。我會嘗試這兩種方法，如果需要的話，我會請託德和伊恩插話。首先是食慾素。首先要明確的是，NT1、NT2和IH之間的區別，並不是基於效力的區別。效力是化合物固有的。到目前為止，臨床工作表明我們對所看到的功效非常滿意。差異可能在於劑量。這實際上為Ib 研究的設計提供了信息，而我提到過，每個患者都作為自己的對照，我們使用維持清醒測試和安慰劑以單劑量形式逐步增加劑量，基本上給出了一條小劑量反應曲線對於每個患者。

And in that way, by starting with the NT1, we anchor the base potency of the compound. And then we have a way to then as we move into NT2s, where we'll begin the dosing in the NT2 with the expectation that we'll have to go a bit higher in NT2s and perhaps in the IHs as well.

這樣，從 NT1 開始，我們就錨定了化合物的基礎效力。然後，當我們進入 NT2 時，我們有辦法做到這一點，我們將開始 NT2 中的劑量，並期望我們必須在 NT2 中提高一點劑量，也許在 IH 中也是如此。

So that's why the NT1 cohort is an anchoring cohort and that's well underway. And so by the end of the year, I expect to have patient exposures in NT1, NT2 at a minimum, perhaps IH as well. How those get assembled into presentation at World Sleep or other scientific meetings is still to be determined, but we're advancing as many of those cohorts as fast as we can in order to inform in Phase II then establishment of those dosing ranges that we use for the differential diagnosis. I hope that makes sense. Does that make sense?

這就是為什麼 NT1 隊列是一個錨定隊列，並且正在順利進行中。因此，到今年年底，我預計患者至少會接觸 NT1、NT2，也許還有 IH。如何將這些數據組合到世界睡眠或其他科學會議上的演示中仍有待確定，但我們正在盡可能快地推進這些隊列，以便在第二階段提供信息，然後確定我們使用的劑量範圍以供鑑別診斷。我希望這是有道理的。那有意義嗎？

Yes. No, that's helpful in terms of thinking about Phase II.

是的。不，這對於思考第二階段很有幫助。

Okay. On the profitability of VIVITROL, I think it's probably the most constructive way to think about it is, it depends on how somebody came into the market. And someone came into the market with a pure generic strategy, i.e., trying to contract at lower rates, we see the business the way it's distributed now across Medicare, Medicaid and commercial. We really see the major opportunity to do that would be in the commercial space, which is only about 20% of the business. I also don't think that would be a particularly smart thing to do because the market is growing and the price point is relatively good.

好的。關於 VIVITROL 的盈利能力，我認為這可能是最具建設性的思考方式，這取決於人們如何進入市場。有人以純粹的通用策略進入市場，即試圖以較低的費率簽訂合同，我們看到該業務現在在醫療保險、醫療補助和商業領域的分佈方式。我們確實看到了實現這一目標的主要機會在商業領域，該領域僅佔業務的 20% 左右。我也不認為這會是一件特別明智的事情，因為市場正在增長，而且價格相對較好。

So our expectation, our hope would be that if someone came in at more like a branded generic at a -- I'm sorry, more like a biosimilar at a high price, to allow the market to continue to grow, we would maintain our promotional intensity. I mean, obviously, we pay attention to the profitability of the brand at all times. But I think the distinction is not between opioid and alcohol. It's more between commercial versus government business. And so we see that the opportunity for entry is more in the commercial space. With that said, the market is so new in alcohol and it's growing so rapidly. The logic for a new entrant into the market, given how hard it is to get into this market would be to come in and continue to grow the market. Todd...

因此，我們的期望，我們的希望是，如果有人以更像是品牌仿製藥的價格進入——對不起，更像是高價的生物仿製藥，為了讓市場繼續增長，我們將維持我們的促銷力度。我的意思是，顯然，我們始終關注品牌的盈利能力。但我認為區別不在於阿片類藥物和酒精。更多的是商業與政府業務之間的關係。所以我們看到進入的機會更多的是商業領域。話雖如此，酒精市場還是一個新興市場，而且增長如此迅速。考慮到進入這個市場的難度，新進入市場的邏輯是進入並繼續發展市場。托德...

Yes, absolutely. Let me just add on to that, Rich, as well. Chris, we made -- I made the statement in our prepared remarks that it's not typical brand to generic erosion. The way to think about this is typically with small molecules, switches in a small molecule switch, you typically see rapid price erosion. And then you also see a focus on point-of-sale switches is typically what happened to a retail pharmacy as well. We don't believe you would see any type of rapid price erosion here. And the way that the fulfillment of the VIVITROL business works is that retail pharmacy is very small. It's less than 20% overall.

是的，一點沒錯。 Rich，讓我補充一下。克里斯，我們做了——我在準備好的發言中聲明，這不是典型的品牌對通用侵蝕的情況。考慮這個問題的方式通常是小分子，小分子開關中的開關，你通常會看到價格快速侵蝕。然後您還會看到零售藥房通常也會關註銷售點開關。我們認為您不會在這裡看到任何類型的快速價格侵蝕。 VIVITROL 業務的實現方式是零售藥店規模非常小。總體來說還不到20%。

You highlight opioid versus alcohol dependence and to Rich's point as well, this actually makes it even more complex, to commercialize the product because those segments actually operate independent and separately. We are really pleased with our strategy over the last couple of years to drive alcohol dependence. In fact, we have approximately 11,000 HCPs now that have written a prescription for VIVITROL and alcohol dependence. And we're seeing about a 5% year-over-year growth with that. Secondly, we're seeing about a 9% demand growth right now for alcohol dependents. So we believe that there's still a lot of runway for VIVITROL within that channel.

您強調了阿片類藥物與酒精依賴，對於里奇的觀點，這實際上使產品商業化變得更加複雜，因為這些細分市場實際上是獨立運作的。我們對過去幾年減少酒精依賴的策略感到非常滿意。事實上，我們現在有大約 11,000 名 HCP 開出了 VIVITROL 和酒精依賴的處方。我們看到同比增長約 5%。其次，我們現在看到酒精依賴者的需求增長了 9%。因此，我們相信 VIVITROL 在該渠道內仍有很大的發展空間。

To Rich's comment as well, too, it's -- we have complex manufacturing. The fulfillment channels are complex, also the settings of care are complex. And there's not 1 setting that actually dominates the market. So anyone coming into the market would have to have a deep understanding of how to commercialize and we believe we are well positioned to continue to drive VIVITROL and also defend if a competitor came into the market.

對於 Rich 的評論，我們的製造也很複雜。履行渠道複雜，護理環境也複雜。並沒有一種環境能夠真正主導市場。因此，任何進入市場的人都必須深入了解如何商業化，我們相信我們有能力繼續推動 VIVITROL 的發展，並在競爭對手進入市場時進行防禦。

That's helpful thinking about the durability of that asset potentially long term. Appreciate it.

這對於思考該資產的潛在長期耐用性很有幫助。欣賞它。

Our next question comes from David Amsellem with Piper Sandler.

我們的下一個問題來自 David Amsellem 和 Piper Sandler。

So on LYBALVI, understanding what you said on commercial payer contracting. So I wanted to ask about the long-term picture. One of your peers that distribute CAPLYTA has talked about more commercial exposure and more contracting. And obviously, that product has a label in bipolar, a different label, but nonetheless, in the bipolar setting. So I guess the question is, what is it left about LYBALVI that's different where you feel like you don't have to contract more aggressively? And longer term, does that change as you're getting more and more exposure to the bipolar population and you're activating more patients. So this is really not a 2023 question, but sort of longer term. And that's number one.

因此，在 LYBALVI 上，了解您所說的商業付款人合同。所以我想問一下長期的情況。您的一位分銷 CAPLYTA 的同行談到了更多的商業曝光和更多的合同。顯然，該產品有一個雙極標籤，一個不同的標籤，但仍然處於雙極環境中。所以我想問題是，LYBALVI 還剩下什麼不同之處，讓你覺得你不必更積極地簽約？從長遠來看，隨著你越來越多地接觸雙相情感障礙人群並且激活更多的患者，這種情況會發生變化嗎？所以這實際上不是 2023 年的問題，而是一個更長期的問題。這是第一。

And then number two, just to be clear on VIVITROL. To the extent there is an early generic entrant, does that put your profitability targets, your long-term profitability targets at risk? And what is the extent to which you can manage the cost structure to continue to maintain those profitability targets to the extent there is an early entrant. Bearing in mind everything you've said, but just wanted to drill down on profitability in case that did come to pass.

然後是第二點，需要明確的是 VIVITROL。如果存在早期仿製藥進入者，這是否會使您的盈利目標、長期盈利目標面臨風險？您可以在多大程度上管理成本結構，以在有早期進入者的情況下繼續維持這些盈利目標。牢記您所說的一切，但只是想深入了解盈利能力，以防這種情況發生。

Yes. So I'll start first with LYBALVI. I would say the way we think about this is we've learned a lot over the last 7 years, specifically with ARISTADA. We've been in this space serious mental illness for a long time. And so we really understand the dynamics that's happening in health systems, the payer environment and with HCPs and one of the things we've learned over time is that you have to be very thoughtful on how you balance volume and profitability.

是的。所以我首先從 LYBALVI 開始。我想說的是，我們思考這個問題的方式是，我們在過去 7 年裡學到了很多東西，特別是在 ARISADA 方面。我們在這個領域已經患有嚴重的精神疾病很長時間了。因此，我們真正了解衛生系統、付款人環境以及 HCP 中正在發生的動態，隨著時間的推移，我們學到的一件事是，必須非常仔細地考慮如何平衡數量和盈利能力。

Once you start offering rebates, especially in the commercial space, you can't retract those rebates. And so we watch that very carefully. We also stay very close to our HCPs and our prescribers. And HCPs and prescribers are very astute at being able to navigate hurdles that are in the space. And so right now, we believe this is a manageable dynamic. So -- and I also want to make sure that we clarify that we do have commercial contracts right now. We do have some commercial contracts.

一旦您開始提供回扣，尤其是在商業領域，您就無法撤回這些回扣。所以我們非常仔細地觀察這一點。我們還與我們的 HCP 和處方醫生保持密切聯繫。醫療保健專業人員和處方醫生非常精明，能夠克服該領域的障礙。所以現在，我們相信這是一個可控的動態。因此，我還想確保我們澄清，我們現在確實有商業合同。我們確實有一些商業合同。

We look at each commercial contract independently. And our focus right now is really making sure that we're maximizing profitability and net revenue for the long time. We do believe that the space will continue to evolve. So our focus, our strategy long term would be to do additional commercial contracts, but at least for the remainder of this year, we think our gross debt and our commercial profile will remain stable.

我們獨立審查每份商業合同。我們現在的重點是確保我們長期實現盈利能力和淨收入最大化。我們確實相信這個領域將繼續發展。因此，我們的重點和長期戰略將是簽訂更多商業合同，但至少在今年剩餘時間內，我們認為我們的總債務和商業狀況將保持穩定。

Thanks, Todd. And then on the profitability question, we intend to manage the business to achieve the profitability targets that we have out there for '24 and '25. I think as you heard, there's a lot of dynamics and they're going to play out certainly with the VIVITROL space, it's really too early to speculate on how things are going to work out. But we're going to continue to assess the situation with the goal of maximizing profitability from the franchise and be able to hit those profitability targets.

謝謝，托德。然後在盈利能力問題上，我們打算管理業務以實現我們為 24 和 25 年制定的盈利目標。我認為正如您所聽到的，有很多動態，它們肯定會在 VIVITROL 空間中發揮作用，現在推測事情將如何發展還為時過早。但我們將繼續評估形勢，目標是最大限度地提高特許經營權的盈利能力，並能夠實現這些盈利目標。

Our next question comes from Paul Matteis with Stifel.

我們的下一個問題來自保羅·馬蒂斯和斯蒂菲爾。

A couple on the Orexin program. Can you talk about just what you've seen in your [dev med] work as it relates to tolerability. Is there anything discernible that drives a maximum tolerated dose for your lead compound and then as we think about the data coming up in NT1 and then also the wakefulness test in other populations against [NT2], IH, how do you think about the predictive validity of that test onto a registrational study in each indication as you extrapolate to things like cataplexy attack, TGI or other endpoints that are relevant in different populations.

一對夫婦正在參加食慾素計劃。您能否談談您在[開發醫學]工作中所看到的與耐受性相關的內容。是否有任何明顯因素可以驅動您的先導化合物的最大耐受劑量，然後當我們考慮 NT1 中出現的數據以及其他人群針對 [NT2] 的覺醒測試時，IH，您如何看待預測有效性當您推斷出猝倒發作、TGI 或與不同人群相關的其他終點等內容時，將該測試納入每個適應症的註冊研究中。

Yes, we haven't hit an MTD yet in the SAD and the MAD, which is encouraging. In fact, based on the way the protocol was designed, we moved off of the SAD to move into the MAD and then Ib, without hitting the MTD. We'll go back and reinterrogate that to make sure we can establish if possible a maximum tolerated dose, which is quite encouraging. As you well know, there are certain, what you expect on target adverse events that you would be looking for that our view is that it looks like the wakefulness component of orexin 2 receptor agonist can be decoupled from some of these other side effects. So that's encouraging.

是的，我們在 SAD 和 MAD 方面尚未達到 MTD，這令人鼓舞。事實上，根據協議的設計方式，我們從 SAD 移至 MAD，然後移至 Ib，而沒有觸及 MTD。我們將返回並重新詢問這一點，以確保我們能夠確定如果可能的話最大耐受劑量，這是相當令人鼓舞的。正如您所知，您對目標不良事件的期望是確定的，我們的觀點是，食慾素 2 受體激動劑的覺醒成分似乎可以與其他一些副作用脫鉤。所以這是令人鼓舞的。

The validity, as you know, the approvable endpoint in registrational studies is this EEG guided maintenance away from the (inaudible). But there are other sleep scores, as you know, qualitative PROs as well as measurements of cataplexy that are useful in NT1, in particular, where Cataplexy is a hallmark feature, not so in NT2. So I think that the anchor, the most predictive for us, we view as the maintenance of wakefulness test, which is, again, not just maintenance away from us. It's also EEG driven. And then we will be collecting these other endpoints in our Phase II study. And then as we line up for the pivotal study, we'll prioritize the primary and secondary endpoints in consultation with FDA and because there are a number of players in this field, there's a certain consensus is building around the way to best assay the efficacy of these drugs to patients.

如您所知，註冊研究中可批准的終點的有效性是腦電圖引導的維護遠離（聽不清）。但正如您所知，還有其他睡眠評分、定性 PRO 以及猝倒測量在 NT1 中很有用，特別是，猝倒是一個標誌性特徵，而在 NT2 中則不然。所以我認為，對我們來說最具預測性的錨，我們認為是清醒測試的維持，這不僅僅是遠離我們的維持。它也是腦電圖驅動的。然後我們將在第二階段研究中收集這些其他終點。然後，當我們準備進行關鍵研究時，我們將與 FDA 協商確定主要和次要終點的優先順序，並且由於該領域有許多參與者，因此圍繞最佳測定療效的方法正在建立一定的共識這些藥物給患者。

And do you still think, Rich, that this compound is likely to address all those populations? Because I think you've spoken previously about the concept of needing to potentially dose higher outside of NT1.

Rich，您仍然認為這種化合物可能適合所有這些人群嗎？因為我認為您之前已經談到過在 NT1 之外可能需要更高劑量的概念。

Yes. I think as I mentioned to Chris earlier, I think the answer to that question will be driven by the potency in NT1. If you have a highly potent compound in NT1, you have the ability then to escalate without much fear even if you had to go 5 to tenfold higher. It's not clear yet in the whole field, how much higher one needs to go in NT2. I think the expectation is that whereas NT1 is clearly a deficiency of orexin-producing neuron and so you have an absence of the orexin peptide entirely.

是的。我想正如我之前向 Chris 提到的，我認為這個問題的答案將由 NT1 的效力決定。如果您在 NT1 中含有高效化合物，那麼您就有能力升級而無需擔心，即使您必須提高 5 到 10 倍。目前還不清楚整個領域，NT2 需要提高多少。我認為預期是 NT1 顯然缺乏產生食慾素的神經元，因此完全缺乏食慾素肽。

NT2 and IH, that differential diagnosis is somewhat fuzzy, but also there may be a continuum or a distribution of orexin tone in the brain. So for certain patients, you might need a certain amount and for another patient you might need more or less. So our hope and our expectation, I'd say right now is that for many patients outside of NT1, you may titrate to effect. And that's the flexibility by potency and allows you to move across a range of doses would be really attractive clinical feature. And that's what we're figuring right now in the clinic.

NT2和IH，鑑別診斷有些模糊，但大腦中食慾素音調也可能存在連續體或分佈。因此，對於某些患者，您可能需要一定的量，而對於其他患者，您可能需要更多或更少。因此，我現在想說的是，我們的希望和期望是，對於 NT1 以外的許多患者，您可以通過滴定來達到效果。這就是效力的靈活性，並允許您在一系列劑量之間移動，這將是真正有吸引力的臨床特徵。這就是我們現在在診所正在考慮的事情。

Our next question comes from Umer Raffat with Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 Umer Raffat。

I just wanted to revisit the long-term guidance 2024 for a quick second. Maybe putting VIVITROL aside for a second. And keeping in mind, obviously, that J&J royalties are not part of the 2024 guidance. Would you agree that the business needs to track north of consensus to make the 20% EBITDA to revenue guidance that you have out there for next year. And again, it could track North either on LYBALVI or you do more of a cost cut. I'm just curious how you're thinking about the key levers to get to those numbers because I'm sure you've thought about it at length.

我只是想快速回顧一下 2024 年長期指導。也許把 VIVITROL 暫時放在一邊。顯然，請記住，強生特許權使用費不屬於 2024 年指導的一部分。您是否同意，企業需要遵循共識，以實現明年 20% 的 EBITDA 佔收入指導。再說一遍，它可以在 LYBALVI 上追踪北方，或者你可以進一步削減成本。我只是好奇你是如何考慮達到這些數字的關鍵槓桿的，因為我確信你已經詳細考慮過它。

Yes, I think as we think about the long-term profitability targets, obviously, they're focused on revenue growth on the top line and then continued focus on disciplined expense management. So it's really a combination of those 2 levers within the business. And we reiterated the guidance when we went out with the J&J news in the June time frame, and we'll talk about them at some point in the future.

是的，我認為，當我們考慮長期盈利目標時，顯然，他們關注的是營收增長，然後繼續關注嚴格的費用管理。所以它實際上是業務中這兩個槓桿的組合。當我們在 6 月份發布強生新聞時，我們重申了這一指導意見，我們將在未來的某個時候討論它們。

Our next question comes from Uy Ear with Mizuho Securities.

我們的下一個問題來自瑞穗證券的 Uy Ear。

So Rich, I think you mentioned that you could be presenting something at World Sleep. And so that's a few months away. Could you sort of give us maybe -- just some color on what we should expect to see the kind of data we expect to see there? And I guess, secondly, on SG&A, I guess if you take out the $28 million one-timer this quarter would be something like $177 million. And have you sort of flatline suggest that you'll spend more than your -- the high end of your guidance. Should we expect SG&A to come down in the second half?

So Rich，我想你提到過你可以在世界睡眠大會上展示一些東西。還有幾個月的時間。您能給我們一些關於我們應該期望看到什麼數據的顏色嗎？其次，我想，在SG&A 方面，我想如果您在本季度一次性拿出2800 萬美元，那麼金額將約為1.77 億美元。您是否有某種平線表明您將花費超過指導的上限。我們是否應該預期 SG&A 會在下半年下降？

World Sleep is in October. And what we're trying to do is enroll as much of the NT1 cohort as possible as well as get into the NT2s as well. We'll see how far along we get as we take those cohorts and compile the data and put it together for a scientific presentation. That will also be coupled with data from the SAD and the MAD study. So we hope to give a pretty comprehensive view of what we've learned in the clinic so far this year. Iain, do you want to take the SG&A?

世界睡眠時間是十月。我們正在努力做的就是盡可能多地招收 NT1 群體，同時也加入 NT2 群體。當我們收集這些隊列並編譯數據並將其放在一起進行科學演示時，我們將看到我們取得了多大的進展。這還將與 SAD 和 MAD 研究的數據相結合。因此，我們希望能夠對今年迄今為止在臨床中學到的知識給出一個相當全面的了解。 Iain，你想參加 SG&A 嗎？

Yes. And then on the SG&A side of things, I think there's really 2 components to that. On the sales and marketing side, as you talked about, we had the investment -- initial investment in DTC, certainly on the TV component side of things. Todd talked about us pulsing that investment as we go through the remainder of the year. Typically, the summer months are a little bit slower from a TV perspective. So we'd expect the DTC spend to come down and then potentially rebound in the fourth quarter as we get into the finale season, assuming the writer and active strike doesn't impact that.

是的。然後在SG&A 方面，我認為實際上有兩個組成部分。在銷售和營銷方面，正如您所說，我們進行了投資——對 DTC 的初始投資，當然是在電視組件方面。托德談到，我們將在今年剩餘時間裡推動這項投資。通常，從電視的角度來看，夏季的時間會稍微慢一些。因此，我們預計 DTC 支出會下降，然後在進入最後一季時可能會在第四季度反彈，假設編劇和積極罷工不會影響這一點。

And then on the G&A side of things, we had a pretty busy Q2, if you think about it, with the J&J arbitration, the Teva litigation, the Annual Shareholder Meeting. So there's a certain level of spend in Q2 that we don't expect to recur in the second half. And then lastly, we also are incurring some spend on the separation of the oncology business, which we wouldn't necessarily expect to run at the same level through the year. So there are a few factors in the second quarter, which we don't anticipate necessarily running through the -- in a similar way through the rest of the year.

然後在一般管理費用方面，如果你仔細想想，我們的第二季度非常繁忙，涉及強生仲裁、梯瓦訴訟和年度股東大會。因此，第二季度有一定水平的支出，我們預計下半年不會再出現這種情況。最後，我們還為腫瘤業務的分離支出了一些支出，我們不一定期望該業務全年保持相同水平。因此，第二季度有一些因素，我們預計這些因素不一定會以類似的方式貫穿今年剩餘時間。

Our next question comes from Marc Goodman with Leerink Partners.

我們的下一個問題來自 Leerink Partners 的 Marc Goodman。

Yes, on that DTC, can you just give us a sense of how you're measuring returns and what you've seen so far as far as return on that investment? And -- and how much money are you planning on spending on the DTC program for the full year?

是的，關於 DTC，您能否讓我們了解一下您如何衡量回報以及您迄今為止所看到的投資回報情況？您計劃全年在 DTC 計劃上花費多少錢？

Yes. Absolutely, Marc. I'll take that. It's early with our DTC investment. We started our digital component of the DTC investment at the beginning of the year, and we were really pleased to launch the TV component in May. Right now, a lot of our metrics are qualitative in nature. So we don't believe that we're seeing any type of inflection on our DTC campaign. We believe that the ROI will play out really over the next 6 to 12 months. .

是的。當然，馬克。我會接受的。我們的 DTC 投資還為時過早。我們在年初開始了 DTC 投資的數字部分，我們很高興在 5 月份推出了電視部分。目前，我們的許多指標本質上都是定性的。因此，我們認為我們的 DTC 活動不會出現任何類型的變化。我們相信投資回報率將在未來 6 到 12 個月內真正發揮作用。 。

The metrics that we're really watching right now are awareness levels, which are building. We're watching our website traffic. We're watching search engine traffic. We're watching overall the number of people that we're able to reach through TRP levels, and they're very consistent with our expectations and the trends are very encouraging as well.

我們現在真正關注的指標是正在建立的意識水平。我們正在觀察我們的網站流量。我們正在觀察搜索引擎流量。我們正在觀察通過 TRP 水平能夠接觸到的總體人數，他們與我們的預期非常一致，而且趨勢也非常令人鼓舞。

In terms of the overall investment, as we've talked about previously, we think the DTC investment on an annual basis for this year will be in the range of about $70 million to $75 million. And then we'll be taking a look at what that investment will look like in '24 and beyond later this year.

就總體投資而言，正如我們之前談到的，我們認為今年DTC的年度投資將在7000萬至7500萬美元左右。然後我們將看看今年晚些時候的 24 年及以後的投資情況。

(Operator Instructions) Our next question comes from Jason Gerberry with Bank of America.

（操作員說明）我們的下一個問題來自美國銀行的 Jason Gerberry。

I just wanted to come back to the 2024 net margin guide of 25%. Mindful that you're waiting to February to address this, but just trying to get conceptually an understanding here because it seems like perhaps 2/3 of the net profit step-up can be achieved through kind of net product sales if they're all kind of operating leverage and the R&D cuts with Mural, but it would seem like you need to take a healthy cut to SG&A. And there's a lot of talk about Pulse investment in DTC. So wondering how much that discretionary SG&A could be a lever in 2024 to get to that net margin guidance? And then just as my follow-up, we're getting some questions just is getting this orexin data at the World Sleep Medical Meeting in October, a priority for you guys?

我只是想回到 2024 年 25% 的淨利潤率指導。請注意，您要等到 2 月份才能解決這個問題，但只是試圖從概念上理解這裡，因為如果全部都是淨產品銷售，似乎可能有 2/3 的淨利潤增長可以通過淨產品銷售來實現某種經營槓桿和研發削減與壁畫，但似乎你需要對SG＆A進行健康削減。關於 Pulse 對 DTC 的投資也有很多討論。那麼想知道 2024 年可自由支配的 SG&A 能在多大程度上成為實現淨利潤率指導的槓桿？然後，正如我的後續行動，我們收到一些問題，就是在 10 月份的世界睡眠醫學會議上獲取食慾素數據，這是你們的首要任務嗎？

So on the profitability targets, again, we'll be providing detailed 2024 guidance on our year-end earnings call in February. To answer all those questions more specifically. But we're anticipating continued growth with the proprietary products, VIVITROL, ARISTADA, and especially LYBALVI driven by the DTC investment that we've talked about. We continue to expect growth in VUMERITY. And then on the expense side of things, as we said, we're very much focused on operating efficiencies that will continue. And we have the ability to flex some of the spend within the P&L, such as DTC, as you alluded to. And as Todd said, we're going to be assessing both the return on investments and the level of investment on DTC as we go forward. But there'll be a lot more detail to follow on that on the February earnings call.

因此，關於盈利目標，我們將在 2 月份的年終收益電話會議上提供詳細的 2024 年指導。更具體地回答所有這些問題。但我們預計專有產品 VIVITROL、ARISTADA，尤其是 LYBALVI 將持續增長，這些產品將受到我們所討論的 DTC 投資的推動。我們繼續預計 VUMERITY 的增長。然後，在費用方面，正如我們所說，我們非常關注將持續的運營效率。正如您提到的，我們有能力在損益表中調整部分支出，例如 DTC。正如托德所說，隨著我們的發展，我們將評估 DTC 的投資回報和投資水平。但二月份的財報電話會議上將會有更多細節公佈。

And Jason, with respect to World Sleep, we expect to present data at World Sleep.

Jason，關於世界睡眠，我們希望在世界睡眠上展示數據。

Okay. That would be the NT1 Phase Ib data at World Sleep.

好的。這就是 World Sleep 的 NT1 Ib 期數據。

Yes, I expect to have at least the first cohorts of the NT1 complete.

是的，我希望至少能完成第一批 NT1。

Our next question comes from Douglas Tsao with H.C. Wainwright. Doug are you there?

我們的下一個問題來自 Douglas Tsao 和 H.C.溫賴特。道格你在嗎？

It appears we don't have any more questions now. So I'm going to turn the floor back over to you, Sandy, for closing comments.

看來我們現在沒有更多問題了。所以我將把發言權交還給你，桑迪，請你發表結束評論。

Great. Thank you, everyone, for joining us on the call today. Please don't hesitate to reach out if there are any follow-up questions we can be helpful with. Thank you.

偉大的。謝謝大家今天加入我們的電話會議。如果有任何我們可以幫助解決的後續問題，請隨時與我們聯繫。謝謝。

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

今天的會議到此結束。此時您可以斷開線路。感謝您的參與。