Alkermes Plc (ALKS) 2026 Q1 法說會逐字稿

Greetings, and welcome to the Alkermes first quarter 2026 financial results conference call. My name is Carrie, and I will be your operator for today's call. (Operator Instructions) Please note, this conference is being recorded.

各位好，歡迎參加 Alkermes 2026 年第一季財務業績電話會議。我是 Carrie，將擔任今天電話會議的接線員。（接線員指示）請注意，本次會議將被錄音。

I will now turn the call over to Sandra Coombs, Senior Vice President of Investor Relations and Corporate Affairs. Sandy, you may now begin.

我現在把電話交給投資人關係與企業事務資深副總裁 Sandra Coombs。Sandy，您可以開始了。

Good morning. Welcome to the Alkermes PLC conference call to discuss our financial results and business update for the quarter ended March 31, 2026.

早安。歡迎參加 Alkermes PLC 電話會議，討論截至 2026 年 3 月 31 日止季度的財務業績與業務更新。

With me today are Richard Popps, our CEO; Joshua Reed, our Chief Financial Officer; Todd Nichols, our Chief Commercial Officer; and Blair Jackson, our Chief Operating Officer.

今天與我一同出席的有我們的執行長 Richard Popps；財務長 Joshua Reed；商務長 Todd Nichols；以及營運長 Blair Jackson。

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 Investor section of alkermes.com. We believe the non-GAAP financial results, in conjunction with the GAAP results, are useful in understanding the ongoing economics of our business. During the quarter, we closed the acquisition of Avadel Pharmaceuticals plc.

我們今天將討論的投影片簡報、新聞稿、相關財務表格，以及 GAAP 與非 GAAP 財務衡量指標之間的調節表，均可於 alkermes.com 的投資人專區取得。我們相信，非 GAAP 財務結果與 GAAP 結果搭配使用，有助於理解我們業務的持續經濟性。本季度我們完成了對 Avadel Pharmaceuticals plc 的收購。

The financial results announced today reflect the mid-February closing of the transaction and the integration of Avadel into our business, including six weeks of contribution from LUMRYZ, Avadel's once-at-bedtime sodium oxybate for the treatment of narcolepsy.

今天公布的財務結果反映了該交易於 2 月中旬完成交割，以及 Avadel 併入我們業務的情況，其中包括 LUMRYZ（Avadel 的每晚睡前一次給藥之 oxybate 鈉，用於治療嗜睡症）六週的貢獻。

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 statement.

本次電話會議的討論將包含前瞻性陳述。實際結果可能與這些前瞻性陳述存在重大差異。請參閱隨附簡報的第 2 頁、我們今早發布的新聞稿，以及我們向 SEC 提交的最新年度報告，其中載有可能導致實際結果與前瞻性陳述所明示或暗示內容產生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.

我們不承擔因新資訊、未來結果或發展而更新或修訂本次電話會議或隨附簡報中所提供資訊的任何義務。

After our prepared remarks, we'll open the call for Q&A, and I'll turn the call over to Richard for some opening remarks.

在我們的準備發言之後，我們將開放問答環節，接著我會把電話交給 Richard 做一些開場致詞。

Thank you, Sandy. Good morning, everyone. So we had an excellent financial first quarter with another strong period of commercial execution and business performance. The quarter was consequential in other ways. Perhaps most significantly, we completed the acquisition of Avadel, a key element of our strategy to become a leader in the fleet medicine space.

謝謝你，Sandy。各位早安。我們第一季財務表現非常出色，商業執行與業務表現再度強勁。本季度在其他方面也具有重要意義。或許最重要的是，我們完成了對 Avadel 的收購，這是我們成為睡眠醫學領域領導者策略中的關鍵要素。

With LUMRYZ, we add a new, differentiated medicine to our portfolio, one that's early in its commercial life and has significant potential for growth. LUMRYZ, addresses a clearly defined patient need and fits logically into our portfolio, consistent with our focus on medicines delivering meaningful clinical benefits to patients.

透過 LUMRYZ，我們為產品組合新增了一款全新且具差異化的藥物；它仍處於商業化早期階段，具有顯著的成長潛力。LUMRYZ 滿足明確界定的病患需求，並且在邏輯上與我們的產品組合高度契合，符合我們聚焦於能為病患帶來具意義臨床效益之藥物的方向。

From a financial standpoint, the acquisition further enhances our financial growth and provides additional resources and flexibility to advance our development portfolio. Beyond the financial consideration, the acquisition allows us to establish a commercial footprint in sleep medicine now, well in advance of the potential approval and launch of alixorexton.

從財務角度來看，這項收購進一步提升我們的財務成長，並提供額外資源與彈性，以推進我們的研發產品組合。除了財務考量之外，這項收購也讓我們得以立即在睡眠醫學建立商業據點，且遠早於 alixorexton 可能獲批與上市之前。

This early presence enables us to engage directly with sleep specialists and other key stakeholders critical to ensuring access to prescribed medications. Building these relationships now provides a strong foundation to accelerate our potential launch trajectory for alixorexton.

這種早期布局使我們能直接與睡眠專科醫師及其他關鍵利害關係人互動，而這些對於確保處方藥物可近性至關重要。現在就建立這些關係，將為我們加速 alixorexton 的潛在上市進程奠定堅實基礎。

Another consequential event occurred at the very end of the quarter, with the announced entry of Eli Lilly into this therapeutic space. This is an important external validation of the breadth of the scientific and commercial potential in developing new medicines targeting the orexin pathway.

另一項重要事件發生在季度末：禮來（Eli Lilly）宣布進入此治療領域。這是對開發靶向 orexin（食慾素）途徑新藥之科學與商業潛力廣度的重要外部驗證。

I think it underscores important aspects of this emerging therapeutic class, namely, the limited number of competitive entrants, and the scarcity of available intellectual property around the chemistry, as well as the broad potential clinical and commercial opportunity. It starts with diseases of hypersomnolence and extends beyond that to a range of potential conditions in neurology, psychiatry, and other rare diseases.

我認為這凸顯了這一新興治療類別的重要特徵：競爭進入者數量有限、可用於相關化學結構的智慧財產權稀缺，以及廣泛的臨床與商業機會。其起點是嗜睡相關疾病，並可延伸至神經科、精神科及其他罕見疾病等多種潛在適應症。

For Alkermes, we believe alixorexton and our other development candidates represent substantial opportunities to advance patient care and drive significant value for shareholders. We have a clear strategy, and we're well-positioned to advance these programs. Blair and I will provide an update on our development efforts at the end of the call.

對 Alkermes 而言，我們相信 alixorexton 以及其他研發候選藥物代表著推進病患照護並為股東創造重大價值的可觀機會。我們有清晰的策略，也具備良好條件推進這些計畫。Blair 和我將在電話會議末段就我們的研發進展提供更新。

But first, I'll turn to Todd and Joshua to review our commercial and financial performance for the first quarter.

不過首先，我將把時間交給 Todd 和 Joshua，回顧我們第一季的商業與財務表現。

Todd.

Todd。

Thank you, Rich. Good morning, everyone. I'm pleased to report that we're off to a strong start to the year, with first-quarter performance ahead of our expectations and solid execution across the commercial organization. It Is exciting to note the evolution of our commercial team as our portfolio of commercial products expands.

謝謝你，Rich。各位早安。我很高興報告，我們今年開局強勁，第一季表現超出預期，商業組織各方面執行穩健。隨著我們商業化產品組合擴大，我們的商業團隊也在持續演進，令人振奮。

We now have commercial capabilities in three distinct categories, in addiction with VIVITROL, in psychiatry with ARISTADA and LYBALVI, and now following the closing of the acquisition of Avadel in sleep medicine with h LUMRYZ. The integration of Avadel commercial team is progressing well, and we entered the second quarter with a combined team fully in place.

我們目前在三個不同類別具備商業能力：成癮領域的 VIVITROL、精神醫學領域的 ARISTADA 與 LYBALVI，以及在完成對 Avadel 的收購後，睡眠醫學領域的 LUMRYZ。Avadel 商業團隊的整合進展順利，我們在第二季開始時已完成整合後的團隊配置。

Looking ahead with clear strategic priorities, a seasoned commercial team, and a portfolio of important medicines in addiction, psychiatry, and sleep disorders, we are in a strong position to deliver on our performance goals for 2026.

展望未來，憑藉清晰的策略優先事項、經驗豐富的商業團隊，以及在成癮、精神醫學與睡眠障礙領域的重要藥物組合，我們具備強勁的條件在 2026 年達成績效目標。

Turning to our first quarter results, net sales from our proprietary product portfolio increased 38% year-over-year to $338.1 million, reflecting solid demand across our psychiatry and addiction portfolios and certain favorable gross to net adjustments during the quarter and six weeks of commercial contribution from LUMRYZ.

回到第一季業績，我們自有產品組合的淨銷售額年增 38% 至 3.381 億美元，反映精神醫學與成癮產品組合的穩健需求、本季度若干有利的毛額轉淨額（gross-to-net）調整，以及 LUMRYZ 六週的商業貢獻。

Starting with VIVITROL, net sales in the quarter were $112.4 million. VIVITROL performance continued to be driven by our ability to capitalize on highly localized market dynamics in certain states and payer systems. Looking ahead, we continue to expect VIVITROL net sales for 2026 in the range of $460 million to $480 million.

先從 VIVITROL 開始，本季度淨銷售額為 1.124 億美元。VIVITROL 的表現持續受惠於我們在某些州與支付方體系中把握高度在地化市場動態的能力。展望未來，我們仍預期 2026 年 VIVITROL 淨銷售額將落在 4.60 億至 4.80 億美元區間。

For our psychiatry franchise, in the first quarter, net sales for the ARISTADA product family were $93.8 million, reflecting solid underlying demand. In 2026, we continue to expect ARISTADA net sales. In the range of $365 million to $385 million. Evolving net sales grew 32% year-over-year to $92.4 million. Underlying TRx growth was 21% year-over-year, driven by sustained momentum in new patient starts and continued expansion in prescriber breadth.

就精神醫學事業群而言，第一季 ARISTADA 產品家族的淨銷售額為 9,380 萬美元，反映穩健的基本需求。2026 年我們仍預期 ARISTADA 淨銷售額將落在 3.65 億至 3.85 億美元區間。LYBALVI 淨銷售額年增 32% 至 9,240 萬美元。基礎 TRx 年增 21%，主要由新病患起始治療的持續動能，以及處方醫師覆蓋面持續擴大所帶動。

Gross to net adjustments were approximately 33%, which we expect will continue to widen into the mid-30s during the course of the year. As we continue to build on our market access profile. For the full year, we continue to expect LYBALVI net sales in the range of $380 million to $400 million.

毛額轉淨額調整約為 33%，我們預期在今年過程中將持續擴大至 30% 中段。隨著我們持續強化市場准入（market access）概況。就全年而言，我們仍預期 LYBALVI 淨銷售額將落在 3.80 億至 4.00 億美元區間。

The first quarter results for these products benefited from gross to net favorability of approximately $14 million, driven primarily by favorable patient mix. Approximately two-thirds of this favorability related to VIVITROL and the remainder related to ARISTADA and LYBALVI. Across the brands, inventory levels in the channel were relatively stable in the first quarter of 2026. As a result, we expect Q1 to Q2 growth trends to generally track end-market demand.

這些產品第一季的結果受惠於約 1,400 萬美元的毛額轉淨額有利因素，主要由較有利的病患組合所驅動。其中約三分之二與 VIVITROL 相關，其餘則與 ARISTADA 與 LYBALVI 相關。就各品牌而言，2026 年第一季通路端庫存水位相對穩定。因此，我們預期第一季到第二季的成長趨勢大致將跟隨終端市場需求。

Turning to our sleep franchise. We are now 10 weeks post-close of the acquisition of Avadel. As we build on our commercial presence in this space, we are pleased with feedback from the sleep medicine community regarding the LUMRYZ commercial organization, the utility and expected durability of the Oxybate class, and the differentiation of LUMRYZ within this category.

接著談睡眠事業群。我們目前距離完成對 Avadel 的收購已 10 週。隨著我們在此領域建立商業布局，我們對睡眠醫學社群對 LUMRYZ 商業組織、Oxybate 類藥物的效用與預期持久性，以及 LUMRYZ 在該類別中的差異化所給予的回饋感到滿意。

The LUMRYZ team is off to a strong start since joining Alkermes. For the first six weeks following the close of the acquisition in mid-February, we recorded Lumrise net sales of $39.5 million. For the full quarter, Lumrise generated approximately $72 million of net revenue.

LUMRYZ 團隊加入 Alkermes 後開局強勁。自 2 月中旬完成交割後的前六週，我們記錄到 LUMRYZ 淨銷售額為 3,950 萬美元。就整個季度而言，LUMRYZ 產生約 7,200 萬美元的淨營收。

We exited the quarter with approximately 3,600 patients on therapy and with solid momentum in new patient enrollments, which we expect to build on as we move through the year. For the full year, we expect LUMRYZ to generate total net sales in the range of $350 million to $370 million. Of this, we expect Alkermes to record $315 million to $335 million, reflecting the period since the mid-February close of the transaction.

我們在季度末時約有 3,600 名病患正在接受治療，新病患加入也呈現良好動能；我們預期在今年推進過程中將持續強化。就全年而言，我們預期 LUMRYZ 的總淨銷售額將落在 3.50 億至 3.70 億美元區間。其中，我們預期 Alkermes 將認列 3.15 億至 3.35 億美元，反映自 2 月中旬交易完成交割以來的期間。

In sleep medicine, our near-term focus is on driving growth and executing against the LUMRYZ opportunity while advancing our broader strategy in the space, including preparation for the potential launch of alixorexton. Narcolepsy and idiopathic hypersomnia represent multi-billion-dollar market opportunities. And our goal is to establish Alkermes as the leader in sleep medicine based on deep expertise in this disease area and differentiated and competitively positioned product portfolio.

在睡眠醫學方面，我們短期重點是推動成長並把握 LUMRYZ 的機會，同時推進我們在該領域的更廣泛策略，包括為 alixorexton 的潛在上市做準備。嗜睡症與特發性嗜睡症代表數十億美元規模的市場機會。我們的目標是憑藉在此疾病領域的深厚專業，以及具差異化且具競爭力定位的產品組合，將 Alkermes 打造成睡眠醫學領域的領導者。

With solid performance from our established franchises and the recent addition of LUMRYZ, we are operating from a strong position of increasing scale and diversification. As we move forward, our focus remains on disciplined execution, driving demand across our brands and advancing our strategy in psychiatry, addiction and sleep medicine. The first quarter was a strong start to the year and we are well positioned as we work toward achieving our 2026 objectives.

憑藉我們既有核心產品線的穩健表現，以及近期新增的 LUMRYZ，我們正處於規模擴大與多元化提升的有利位置。展望未來，我們仍將專注於嚴謹的執行力，推動旗下各品牌需求成長，並推進我們在精神醫學、成癮治療與睡眠醫學方面的策略。第一季為今年奠定了強勁開局，朝向達成 2026 年目標的過程中，我們已具備良好條件。

With that, I will pass the call to Joshua to review the financial results for the quarter.

接下來，我將把電話會議交給 Joshua，請他回顧本季的財務結果。

Thank you, Todd. In the first quarter, we delivered financial results that reflect continued growth across our proprietary product portfolio and the initial contribution from LUMRYZ following the close of the Avadel acquisition. Post-acquisition, our financial profile is further enhanced and diversified. We manage the business to drive significant operating cash flow and maintain a strong balance sheet, and we do so now with increased scale and flexibility. We are in a strong position to invest in the expanding development pipeline that will shape the future of our business.

謝謝你，Todd。第一季我們交出反映持續成長的財務成果，成長動能來自我們自有產品組合的擴張，以及完成 Avadel 收購後 LUMRYZ 的初步貢獻。收購完成後，我們的財務結構進一步強化並更加多元。我們以推動顯著的營運現金流並維持強健的資產負債表為目標來管理業務，而如今在規模與彈性提升的情況下更能做到這一點。我們具備優勢，可投資於持續擴大的研發管線，這將塑造公司未來。

Turning to our financial results. During the quarter, we generated total revenues of $392.9 million. These results provide a solid foundation for the year. Today, we are updating certain non-cash elements of our 2026 financial expectations to reflect refinements to the purchase price accounting for the acquisition of Avadel. These adjustments improve our full-year expectations for GAAP net loss and EBITDA.

接著說明財務結果。本季我們創造總營收 3.929 億美元，為全年奠定穩固基礎。今天，我們更新 2026 年財務展望中的部分非現金項目，以反映對 Avadel 收購案購買價格分攤（purchase price accounting）的精細化調整。這些調整改善了我們對全年 GAAP 淨損與 EBITDA 的預期。

For our portfolio of proprietary products, we generated net sales of $338.1 million ahead of the expectations we outlined on our fourth quarter call. As we move into the second quarter, we expect Q2 net sales from our proprietary portfolio, including a full quarter of revenues from LUMRYZ in the range of $385 million to $405 million.

就自有產品組合而言，我們實現淨銷售額 3.381 億美元，高於我們在第四季電話會議中所提出的預期。進入第二季後，我們預期自有產品組合（包含 LUMRYZ 全季營收）的 Q2 淨銷售額將落在 3.85 億至 4.05 億美元之間。

Manufacturing royalty revenues were $54.8 million for the quarter, including revenues of $27.3 million from VUMERITY and $18 million from the long-acting and INVEGA products.

本季製造權利金收入為 5,480 萬美元，其中包含來自 VUMERITY 的 2,730 萬美元，以及來自長效型與 INVEGA 產品的 1,800 萬美元。

Turning to expenses. Cost of goods sold were $61.6 million, which includes the purchase price accounting of LUMRYZ inventory. Recall that at closing, LUMRYZ inventory held by Avadel was marked to fair market value. Net of the LUMRYZ inventory step-up charge, cost of goods sold would have been $48.9 million in Q1 of this year, compared to $49.2 million in Q1 of the prior year.

接著看費用。銷貨成本為 6,160 萬美元，其中包含 LUMRYZ 存貨的購買價格分攤影響。請回想在交割時，Avadel 持有的 LUMRYZ 存貨已調整（重估）至公允市價。扣除 LUMRYZ 存貨增值（step-up）費用後，今年第一季的銷貨成本本應為 4,890 萬美元，與去年第一季的 4,920 萬美元相比。

In the second quarter, we expect COGS to be in the range of $85 million to $95 million reflecting a full quarter of LUMRYZ sales and associated inventory step-up charge.

第二季我們預期銷貨成本將落在 8,500 萬至 9,500 萬美元之間，反映 LUMRYZ 全季銷售以及相關的存貨增值（step-up）費用。

R&D expenses in the quarter were $103.3 million, compared to $71.8 million in Q1 of the prior year, reflecting the initiation of the alixorexton Brilliance Phase III clinical program in narcolepsy, which began in the first quarter, the ongoing Vibrance III Phase II study of alixorexton in idiopathic hypersomnia, and the Phase I studies and development efforts for our next orexin-2 receptor agonist candidates, ALKS 7290 and ALKS 4510. In the second quarter, we expect R&D expenses to be in the range of $110 to $120 million.

本季研發費用為 1.033 億美元，去年第一季為 7,180 萬美元；主要反映我們在第一季啟動 alixorexton 用於嗜睡症（narcolepsy）的 Brilliance 第三期臨床計畫、持續進行 alixorexton 用於特發性嗜睡症（idiopathic hypersomnia）的 Vibrance III 第二期研究，以及針對下一代 orexin-2 受體致效劑候選藥物 ALKS 7290 與 ALKS 4510 的第一期研究與開發工作。第二季我們預期研發費用將落在 1.10 億至 1.20 億美元之間。

SG&A expenses were $264.6 million for the quarter, which included approximately $55 million of costs associated with the closing of the acquisition of Avadel, including transaction expenses and share-based compensation. Excluding these one-time expenses, SG&A would have been $209.4 million compared to $171.7 million in Q1 of last year, primarily reflecting the addition of the Avadel commercial infrastructure mid-quarter.

本季銷售、一般及行政（SG&A）費用為 2.646 億美元，其中包含約 5,500 萬美元與 Avadel 收購案交割相關的成本，包括交易費用與股份基礎給付。排除這些一次性費用後，SG&A 將為 2.094 億美元，去年第一季為 1.717 億美元；主要反映本季中期納入 Avadel 的商業化基礎設施。

As we look ahead to the second quarter, we expect SG&A expense to be in the range of $210 million to $220 million. During the quarter, we also recorded amortization of intangibles of $11.7 million and net interest expense of $12.4 million.

展望第二季，我們預期 SG&A 費用將落在 2.10 億至 2.20 億美元之間。本季我們亦認列無形資產攤銷 1,170 萬美元，以及淨利息費用 1,240 萬美元。

In Q1, we generated GAAP net loss of $66.5 million and EBITDA of minus $30.1 million. We also generated positive adjusted EBITDA of $80.3 million, well ahead of our prior Q1 expectation of adjusted EBITDA of $30 million to $50 million due to higher-than-expected revenues and the timing of R&D expenses. Looking ahead to the second quarter, we expect adjusted EBITDA to be in the range of $100 million to $120 million.

第一季我們的 GAAP 淨損為 6,650 萬美元，EBITDA 為負 3,010 萬美元。我們也產生正向的調整後 EBITDA 8,030 萬美元，明顯高於先前對第一季調整後 EBITDA 3,000 萬至 5,000 萬美元的預期，原因在於營收高於預期以及研發費用認列時點的影響。展望第二季，我們預期調整後 EBITDA 將落在 1.00 億至 1.20 億美元之間。

Turning to our balance sheet. We ended the first quarter with approximately $538 million in cash in total investments. To finance the acquisition of Avadel, we used approximately $775 million of cash from our balance sheet and entered into term loans totaling $1.525 billion due in 2031. We expect to pay down this debt quickly with cash flows from the business.

接著看資產負債表。我們在第一季末持有約 5.38 億美元的現金及總投資。為了籌措 Avadel 收購案，我們動用資產負債表上約 7.75 億美元現金，並簽訂總額 15.25 億美元、2031 年到期的定期貸款。我們預期將以公司營運現金流快速償還該債務。

During the quarter, we also deployed $28 million to repurchase approximately 1 million shares at an average price of approximately $28 per share. We continue to have $172 million of remaining share repurchase authorization.

本季我們亦投入 2,800 萬美元回購約 100 萬股股票，平均回購價格約為每股 28 美元。我們目前仍有 1.72 億美元的剩餘庫藏股回購授權額度。

As I mentioned, in connection with the purchase price accounting related to the Avadel acquisition, we have refined our expectations for several non-cash expense items, including the inventory step-up charge, which flows through cost of goods sold, and the amortization of intangible assets associated with LUMRYZ. These changes have a net positive impact on our 2026 expectations for GAAP net loss and EBITDA. We now expect to expense approximately $105 million of LUMRYZ inventory fair value step-up in 2026, compared to a prior estimate of approximately $150 million.

如我先前提到，與 Avadel 收購案相關的購買價格分攤之下，我們已精細化調整數項非現金費用項目的預期，包括會反映在銷貨成本中的存貨增值（step-up）費用，以及與 LUMRYZ 相關的無形資產攤銷。這些變動對我們 2026 年 GAAP 淨損與 EBITDA 的預期帶來淨正面影響。我們目前預期 2026 年將認列約 1.05 億美元的 LUMRYZ 存貨公允價值增值費用，先前估計約為 1.50 億美元。

As a result, our 2026 cost of goods sold is now expected to be $320 million to $340 million, an improvement from our prior estimate of $365 million to $385 million. For amortization of intangible assets, we now expect full-year amortization expense in the range of $75 to $85 million, compared to our previous estimate of $95 to $105 million. For income tax, we now expect no income tax expense or benefit for the year from a prior estimate of an income tax benefit of $20 million.

因此，我們目前預期 2026 年銷貨成本為 3.20 億至 3.40 億美元，較先前估計的 3.65 億至 3.85 億美元有所改善。就無形資產攤銷而言，我們目前預期全年攤銷費用將落在 7,500 萬至 8,500 萬美元之間，先前估計為 9,500 萬至 1.05 億美元。就所得稅而言，我們目前預期全年不會有所得稅費用或利益，先前估計為 2,000 萬美元的所得稅利益。

Taken together, these purchase price accounting adjustments improve our expectations for GAAP net loss, which is now projected to be in the range of $70 million to $90 million, as well as for EBITDA, which is now expected to be in the range of positive $105 million to $135 million.

綜合而言，這些購買價格分攤調整改善了我們對 GAAP 淨損的預期，目前預估將落在 7,000 萬至 9,000 萬美元之間；同時也改善了 EBITDA 的預期，目前預期將落在正 1.05 億至 1.35 億美元之間。

All other components of our 2026 outlook, including adjusted EBITDA, remain unchanged. Taking a step back, it was a strong start to the year, and we look forward to carrying this momentum into the second quarter and beyond.

我們 2026 年展望的其他所有組成項目（包括調整後 EBITDA）維持不變。回過頭來看，今年開局強勁，我們期待將這股動能延續至第二季及之後。

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

接下來，我把電話會議交回給 Rich。

Thank you, Joshua. So the commercial and financial elements of the business are strong. With expected revenue of more than $1.7 billion and adjusted EBITDA of more than $370 million, we have the financial resources to invest aggressively in our pipeline and generate significant cash flow.

謝謝你，Joshua。因此，公司的商業面與財務面都很強勁。在預期營收超過 17 億美元、調整後 EBITDA 超過 3.70 億美元的情況下，我們具備財務資源，可積極投資研發管線並創造可觀的現金流。

I think it's becoming increasingly clear that our Orexin program has brought us to the threshold of substantial value creation. Today, we've developed and shared with you comprehensive clinical data sets across the first area of focus for this therapeutic class, disorders of hypersomnolence.

我認為愈來愈清楚的是，我們的 Orexin 計畫已將我們帶到創造重大價值的門檻。今天，我們已就此治療類別的第一個重點領域——嗜睡相關障礙（disorders of hypersomnolence）——建立並與各位分享完整的臨床資料集。

That data set reflects the design and execution of a broad Phase II program, randomized, controlled, multi-center, multi-week across multiple doses and indications. Using established clinical endpoints, as well as additional measures such as fatigue and cognition that relate specifically to the brain circuitry that we're activating.

該資料集反映一項廣泛的第二期計畫之設計與執行：隨機、對照、多中心、跨多週期，涵蓋多個劑量與適應症。我們採用既定的臨床終點，同時也納入額外衡量指標，例如疲勞與認知，這些指標與我們所啟動的大腦迴路特別相關。

At the same time, we're broadening our development efforts beyond disorders of hypersomnolence, leveraging our portfolio of orexin-2 receptor agonist candidates. In this area, more than most, we believe that chemistry-based intellectual property represents an important strategic asset. Blair will speak in more detail about our expansion strategy and development plans. But first, I'm going to update you on where we are with alixorexton.

同時，我們也正將開發工作擴展至嗜睡相關障礙以外的領域，並運用我們的 orexin-2 受體致效劑候選藥物組合。在這個領域，我們比多數情況更相信，以化學為基礎的智慧財產權是重要的策略資產。Blair 將更詳細說明我們的擴張策略與開發計畫。不過首先，我將更新 alixorexton 的最新進展。

This year, our focus is on continuing the momentum we built in Phase II to enroll the Phase III brilliance studies in narcolepsy. Phase III, for us, is all about execution. We're on the path now to potential registration. The Brilliance Phase III program is now open for enrollment in narcolepsy Type I and Type II, with site initiation and patient screening underway. Because of the strength of the Phase II results, investigator interest in the studies is strong.

今年我們的重點是延續第二期所建立的動能，推進嗜睡症第三期 Brilliance 研究的收案。對我們而言，第三期的核心在於執行。我們目前正走在可能取得註冊（registration）的路徑上。Brilliance 第三期計畫現已開放嗜睡症第一型與第二型的收案，並已啟動研究中心並進行受試者篩選。由於第二期結果強勁，研究者對這些研究的興趣相當高。

We're working to enroll these studies quickly, with a sharp focus on quality and execution to support the strongest competitive positioning. From an operational perspective, the duration and scale of the Vibrance Phase II studies generated important and proprietary data that informed the design of our Phase III program.

我們正努力加速這些研究的收案，同時高度聚焦於品質與執行，以支持最強的競爭定位。從營運角度來看，Vibrance 第二期研究的期間與規模產生了重要且具專屬性的資料，並為我們第三期計畫的設計提供了依據。

With alixorexton, we're building a broad and robust clinical data package across narcolepsy and idiopathic hypersomnia. In June, we'll present data from the vibrance II narcolepsy Type II study at the annual SLEEP meeting in Baltimore.

透過 alixorexton，我們正在於嗜睡症與特發性嗜睡症兩大領域建立廣泛且穩健的臨床資料套件。6 月，我們將在巴爾的摩舉行的年度 SLEEP 會議上，發表 Vibrance II 嗜睡症第二型（Type II）研究的數據。

We've reported the positive top-lines in November, so much of the data set will be familiar to you. Along with the positive outcome of the study, Vibrance II is important because it's one of a very small number of clinical studies ever conducted exclusively in patients with NT2.

我們已於 11 月公布正向的頂線結果，因此資料集中的多數內容對各位而言將不陌生。除了研究的正向結果之外，Vibrance II 之所以重要，是因為它是極少數曾經「僅」在 NT2 患者中進行的臨床研究之一。

As such, it provides a depth of insight into the characteristics and variability of this population that is largely absent from the existing literature. The SLEEP meeting gives us an opportunity to share the data with a broader sleep community. One-on-one engagements with clinicians and investigators over the last several months have already given us a clear sense of the treatment community's high level of interest and excitement about these data.

因此，它提供了對此族群特徵與變異性的深入洞見，而這些在既有文獻中多半付之闕如。SLEEP 會議讓我們有機會與更廣泛的睡眠醫學社群分享這些數據。過去數月我們與臨床醫師與研究者的一對一交流，也已讓我們清楚感受到治療社群對這些數據抱持高度興趣與期待。

For idiopathic hypersomnia, or IH, our Vibrance III Phase II study is ongoing and on track to be completed in the fourth quarter of this year. We've initiated enrollment of a split-dose cohort of approximately 30 patients across sites in both US and Europe, with patients randomized to alixorexton or a matching split-dose placebo.

在特發性嗜睡症（idiopathic hypersomnia，IH）方面，我們的 Vibrance III 第二期研究正在進行中，並按計畫於今年第四季完成。我們已在美國與歐洲的多個中心啟動約 30 名患者的分次給藥（split-dose）隊列收案，患者將隨機分派接受 alixorexton 或相符的分次給藥安慰劑。

As a reminder,in IH, the Epworth Sleepiness Scale and the Idiopathic Hypersomnia Severity Scale are the established and preferred clinical and regulatory endpoints. In addition to those measures, Vibrance-3 also includes mean sleep latency assessed by the Maintenance of Wakefulness Test, Which will help us to characterize the durability of wakefulness over the course of the day.

提醒一下，在 IH 中，Epworth 嗜睡量表（Epworth Sleepiness Scale）與特發性嗜睡症嚴重度量表（Idiopathic Hypersomnia Severity Scale）是既定且偏好的臨床與法規端點。除上述量測外，Vibrance-3 亦納入以清醒維持測試（Maintenance of Wakefulness Test）評估的平均入睡潛伏期（mean sleep latency），這將協助我們刻畫清醒狀態在一天當中的持久性。

The clinical development program for alixorexton has been deliberately designed to support strong competitive positioning, both in the quality of the clinical data generated and the breadth of potential dosing options and regimens being evaluated to address individual patient needs.

alixorexton 的臨床開發計畫是經過審慎設計，以支持強而有力的競爭定位，包含所產生臨床數據的品質，以及為滿足個別患者需求而評估的多元潛在劑量選項與給藥方案之廣度。

We believe this approach positions alixorexton, if approved, to become the orexin of choice across both narcolepsy indications. Importantly, alixorexton has the potential to be the first in class in narcolepsy type 2, and our lead in development in NT2 continues to widen.

我們相信，若獲核准，此一策略將使 alixorexton 有望成為涵蓋兩項嗜睡症適應症的首選食慾素（orexin）療法。重要的是，alixorexton 具有在嗜睡症第二型中成為同類首創（first-in-class）的潛力，而我們在 NT2 的開發領先優勢也持續擴大。

In the meantime, while the orexin development story in narcolepsy continues to mature, with LUMRYZ, we now have an important new medicine being used in current clinical practice. Later this quarter, we expect to announce top-line data from the LUMRYZ Phase III REVITALIZE study in IH.

同時，在嗜睡症的食慾素開發故事持續成熟之際，透過 LUMRYZ，我們如今已有一項重要的新藥正在現行臨床實務中使用。本季稍晚，我們預期將公布 LUMRYZ 於 IH 的第三期 REVITALIZE 研究之頂線數據。

Data from this double-blind, placebo-controlled, randomized withdrawal study, which enrolled approximately 150 patients, would serve as the basis for an sNDA submission with a potential launch in early 2028 if approved. This represents a potential growth opportunity for LUMRISE in an underserved patient population, and we'll look forward to data this quarter.

這項雙盲、安慰劑對照、隨機撤藥研究共納入約 150 名患者，其數據將可作為提交補充新藥申請（sNDA）的基礎；若獲核准，潛在上市時間可能在 2028 年初。這代表 LUMRYZ 在一個醫療資源不足的患者族群中具備潛在成長機會，我們也期待本季的數據。

So now I'll turn the call over to Blair to provide an update on our expanding development work in our orexin portfolio. Beyond central disorders of hypersomnolence, there are many adjacent disease areas that may benefit from modulating the orexin pathway. We identified this opportunity early on, and we're moving aggressively with new molecules.

接下來我把電話交給 Blair，請他更新我們在食慾素產品組合中持續擴大的開發工作。除了中樞性嗜睡障礙之外，還有許多相鄰疾病領域可能受益於調節食慾素途徑。我們很早就辨識到這個機會，並正積極推進新分子。

Go ahead, Blair.

Blair，請。

Thank you, Rich. As we outlined earlier in January, this year we are expanding our orexin development programs into disease areas outside of sleep medicine. We are doing so with two new molecules from our portfolio, ALKS 7290 and ALKS 4510. Each of these orexin-2 receptor agonists has been advancing through single and multiple ascending dose cohorts in healthy volunteers, and we are pleased with the profiles we have observed to date. This year, our development plans take us into patient populations in ADHD and fatigue.

謝謝你，Rich。如同我們在 1 月較早時所概述的，今年我們正將食慾素開發計畫擴展至睡眠醫學以外的疾病領域。我們將以產品組合中的兩個新分子 ALKS 7290 與 ALKS 4510 來推進。這兩者皆為食慾素-2 受體致效劑（orexin-2 receptor agonists），目前已在健康受試者中完成單次與多次遞增劑量（single and multiple ascending dose）隊列的推進，我們對迄今觀察到的特性表現感到滿意。今年，我們的開發計畫將進入 ADHD 與疲勞的患者族群。

Early on, based on our emerging data and feedback from clinical investigators, we identified Attention Deficit Hyperactivity Sisorder as one of the most compelling initial opportunities for orexin-2 receptor agonists outside of sleep medicine.

在早期，基於我們逐步浮現的數據以及臨床研究者的回饋，我們將注意力不足過動症（Attention Deficit Hyperactivity Disorder，ADHD）辨識為食慾素-2 受體致效劑在睡眠醫學之外最具吸引力的初始機會之一。

ADHD is a common neurodevelopmental disorder characterized by persistent difficulty in maintaining attention and concentration and is frequently accompanied by hyperactive and impulsive behavior. Despite the availability of some treatment options, many patients continue to experience residual symptoms, functional impairment, tolerability issues, and adherence challenges, even when receiving current standard of care treatment.

ADHD 是一種常見的神經發展障礙，其特徵為持續難以維持注意力與專注，且常伴隨過動與衝動行為。儘管已有一些治療選項，許多患者即使接受現行標準治療，仍持續出現殘餘症狀、功能受損、耐受性問題與用藥依從性挑戰。

Against that backdrop, Alkermes is working to advance the evidence base supporting the potential use of orexin-2 receptor agonists in ADHD. We have established a foundation of data from validated preclinical behavioral models, assessment of neurotransmitters, and human EEG that support our conviction in this program. Based on this foundation, we are initiating our first clinical studies of ALKS 7290 in adults with ADHD this year.

在此背景下，Alkermes 正致力於推進支持食慾素-2 受體致效劑在 ADHD 潛在用途的證據基礎。我們已建立一套資料基礎，包含經驗證的臨床前行為模型、神經傳導物質評估，以及人體腦電圖（EEG）結果，支持我們對此計畫的信念。基於這些基礎，我們將於今年啟動 ALKS 7290 在成人 ADHD 的首批臨床研究。

The first is a Phase 1b randomized placebo-controlled proof-of-concept study designed to enroll approximately 50 adult patients. Participants will receive two weeks of treatment with ALKS 7290 or placebo. In this study, we will assess the safety and tolerability of ALKS 7290, along with the effects of treatment on translational measures where we expect to see more rapid changes, including quantitative EEG and certain neuropsychological performance measures.

第一項為第 1b 期、隨機、安慰劑對照的概念驗證研究，預計收納約 50 名成人患者。受試者將接受 ALKS 7290 或安慰劑為期兩週的治療。在此研究中，我們將評估 ALKS 7290 的安全性與耐受性，並評估治療對轉譯性量測指標的影響；我們預期這些指標能更快速反映變化，包括定量腦電圖（quantitative EEG）以及部分神經心理學表現量測。

These assessments are designed to evaluate sustained attention, vigilance, and impulse control in a shorter duration study. For exploratory purposes, we'll also assess changes from baseline on established clinical ADHD scales. Results from this Phase 1b study are expected in the fourth quarter of this year, and we will provide the first clinical data generated with the Rexin-2 receptor agonist in patients with ADHD.

這些評估旨在於較短期的研究中，衡量持續性注意力、警覺性與衝動控制。出於探索性目的，我們也將評估既定 ADHD 臨床量表相較基線的變化。此第 1b 期研究結果預計於今年第四季出爐，並將提供首批在 ADHD 患者中使用食慾素-2 受體致效劑所產生的臨床數據。

Enrollment in that study is already underway, with the first patients dosed in April. As enrollment in the Phase 1b study progresses, we plan to initiate a well-powered Phase 2 study in adult patients with ADHD this summer.

該研究的收案已在進行中，且首批患者已於 4 月給藥。隨著第 1b 期研究收案推進，我們計畫於今年夏季啟動一項具充分統計效力的第 2 期研究，對象為成人 ADHD 患者。

This randomized, double-blind study is expected to enroll approximately 300 patients and will evaluate ALKS 7290 versus placebo over a four-week treatment period. The primary endpoint will be changed from baseline in the Adult ADHD Investigator Rating Scale. Data from this study, which we expect to complete in 2027, may serve as the foundation to advance to a potential registrational program in ADHD.

這項隨機、雙盲研究預計收納約 300 名患者，並將在四週治療期間評估 ALKS 7290 相較安慰劑的效果。主要終點將為成人 ADHD 研究者評分量表（Adult ADHD Investigator Rating Scale）相較基線的變化。本研究預計於 2027 年完成，其數據可能作為推進至 ADHD 潛在註冊性（registrational）計畫的基礎。

We are excited to be the leaders in this exciting area of clinical development, and we look forward to updating you on our progress. We are advancing in single and multiple ascending dose studies in healthy volunteers and plan to initiate a multi-dose Phase EBITDA study later this year in patients with fatigue associated with multiple sclerosis and Parkinson's disease.

我們很高興能在這個令人振奮的臨床開發領域中扮演領導者，並期待向各位更新我們的進展。我們也正於健康受試者中推進單次與多次遞增劑量研究，並計畫於今年稍晚在與多發性硬化症及帕金森氏症相關的疲勞患者中，啟動一項多劑量的第 2 期研究。

Fatigue is one of the most common and burdensome symptoms in neurodegenerative disorders and remains a significant unmet need in MS and Parkinson's. Our interest in fatigue in these populations is also informed by observations from our Phase II narcolepsy studies, where we saw improvements in patient-reported fatigue that appeared distinct from effects on sleepiness or wakefulness alone.

疲勞是神經退化性疾病中最常見且負擔最重的症狀之一，在多發性硬化症（MS）與帕金森氏症中仍存在顯著未被滿足的醫療需求。我們對這些族群疲勞的興趣，也受到我們第 2 期嗜睡症研究觀察的啟發：我們看到患者回報的疲勞有所改善，且該改善似乎不同於僅對嗜睡或清醒狀態的影響。

Fatigue represents a novel area of pharmaceutical development, and we will provide more details regarding the design of the development program as the Phase II study opened later this year. As we advance through the development program, our strategy will be stepwise, data-driven, and informed by interactions with regulatory authorities as we seek to make a meaningful contribution to patient care.

疲勞代表一個新穎的藥物開發領域；隨著今年稍晚第 2 期研究啟動，我們將提供更多關於開發計畫設計的細節。隨著開發計畫推進，我們的策略將採取循序漸進、以數據驅動，並在尋求對患者照護做出有意義貢獻的同時，參考與法規主管機關互動所獲得的資訊。

Taking a step back, the potential utility of orexin 2 receptor agonists across a broad range of indications is a significant and striking opportunity. This will be the year that we generate a substantial new increment of data to the clinical evidence base supporting these potential opportunities.

退一步來看，食慾素 2 受體致效劑在廣泛適應症上的潛在效用，是一個重大且引人注目的機會。今年將是我們為支持這些潛在機會的臨床證據基礎，產出大量新增數據的一年。

With that, I'll turn the call back to Sandy to manage the Q&A.

接下來，我把電話交回給 Sandy 來主持問答。

Thanks, Claire. We'll now open the call for Q&A.

謝謝你，Claire。我們現在開始進行問答。

Thank you. We will now be conducting a question-and-answer session. (Operator Instructions)

謝謝。我們現在將進行問答環節。（接線員指示）

David Amsellem, Piper Sandler.

David Amsellem，Piper Sandler。

Thanks. So on the Orexin programs beyond Sleep Wake in ADHD, can you talk about your thought process regarding development as monotherapy versus adjunctive therapy in ADHD and how your, what preclinical data you can point to that gives you confidence that a monotherapy approach makes sense? And then regarding the fatigue program, might be a little early to talk to this, but can you talk about endpoints that you're exploring? And I realize this is going to be informed by your discussions with regulators, but what are you going to be looking at in terms of early outcome measures on fatigue? Thanks.

謝謝。關於睡眠—清醒領域以外、在 ADHD 的食慾素計畫，你們能否談談在 ADHD 開發上，作為單藥治療（monotherapy）相較於加成治療（adjunctive therapy）的思考脈絡？以及有哪些臨床前數據能讓你們有信心，認為單藥治療的策略是合理的？另外，關於疲勞計畫，或許現在談還稍早，但你們能否談談正在探索的終點？我理解這會受到你們與法規單位討論的影響，但就疲勞而言，你們在早期結果量測上會著重觀察哪些指標？謝謝。

Sure. Hey, David, it's Blair. So with regards to ADHD, we have a substantive amount of data with regards to orexin agonists in this space. And in fact, it's probably the most tangential of the indications out there for the next place for us to go. We did a lot of preclinical work looking at neurotransmitter release, looking at behavioral models, EEG. We saw, increased levels of acetylcholine in the prefrontal cortex, which is a high indication of activity and attentiveness.

當然。嗨，David，我是Blair。關於ADHD，我們在這個領域針對食慾素（orexin）致效劑累積了相當大量的數據。事實上，就我們下一步可能前進的方向而言，這可能是目前各項適應症中相對最「旁支」的一個。我們做了很多臨床前研究，觀察神經傳導物質釋放、行為模型以及腦電圖（EEG）。我們看到前額葉皮質的乙醯膽鹼濃度上升，這是活動性與專注度提高的高度指標。

We also use what is really a highly translatable model within the preclinical testing, where it's called the five-choice serial reaction test. And our initial hypothesis was exactly where you started, was what if we did an adjunctive therapy, perhaps with a non-stimulant? Would that provide a really beneficial outcome? But when we did that model, what we found is across all our studies, we were performing as well as or better than stimulants themselves as a monotherapy. So we feel that both in the attention and the impulsivity aspects of those programs, that we have a really good opportunity here.

我們也使用一個在臨床前測試中其實高度可轉譯的模型，稱為五選序列反應測試（five-choice serial reaction test）。我們最初的假設正如你一開始提到的：如果我們做一個加成治療（adjunctive therapy），例如搭配非興奮劑，是否能帶來非常有利的結果？但在該模型中，我們發現，在所有研究中，作為單一療法（monotherapy）時，我們的表現與興奮劑相當，甚至更好。因此我們認為，無論是在注意力或衝動性這兩個面向，我們在這裡都有非常好的機會。

And our clinical studies that we're kicking off are actually designed to look at just that. So we'll be looking at monotherapy across a broad population, both in tension and impulsivity. And I think the two studies that we've set up are going to be really well positioned to give us a full idea of how this could proceed moving forward.

而我們即將啟動的臨床研究，其實就是為了檢驗這一點而設計的。因此我們將在廣泛族群中評估單一療法，同時涵蓋注意力與衝動性。我認為我們設計的兩項研究，將能讓我們非常到位地掌握未來推進的全貌。

With regards to fatigue. And that program. We're moving into the clinic with a drug called ALKS 4510. And that's a really interesting area. And we are looking very carefully at the scales to be used within those studies. So we're going to be testing this in MS fatigue patients and Parkinson's disease patients. And one. Scale that we're going to use is the PROMIS fatigue scale.

關於疲勞，以及那個計畫。我們正以一款名為ALKS 4510的藥物推進到臨床。這是一個非常有意思的領域。我們也非常仔細地評估這些研究中要使用的量表。因此我們將在多發性硬化症（MS）疲勞患者與帕金森氏症患者中進行測試。我們將使用的一個量表是PROMIS疲勞量表。

This is a scale that we used in our NT1 study, where we showed a really strong benefit within the NT1 patients, taking them really from severe to normal on that scale. And that hasn't been shown very widely within clinical literature. We also saw similar outcomes as we moved into the NT2 patient population, so that bodes well as we go to an intact orexin tone system.

這個量表我們在NT1研究中用過，當時我們在NT1患者身上顯示出非常強的效益，讓他們在該量表上幾乎從「嚴重」改善到「正常」。這在臨床文獻中並不常見。我們在推進到NT2患者族群時也看到類似結果，因此當我們進入一個食慾素張力（orexin tone）系統完整的情境時，這是個好兆頭。

But the other thing to keep in mind is a lot of these disease areas, they also have their own scales that have been developed as part of that patient population. So we're going to be testing those two and trying to understand best how the different characteristics of the scales work, and also how these drugs perform within different subcategories of fatigue.

但另外要記住的是，許多這些疾病領域也都有針對其患者族群所開發的專屬量表。因此我們會同時測試這兩類量表，並嘗試理解不同量表特性的最佳運作方式，以及這些藥物在不同疲勞子類別中的表現。

Umer Raffat, Evercore ISI.

Umer Raffat，Evercore ISI。

Hi guys, thanks for taking my question. I have a two-part question. And clearly there's been a ton of interest, strategic interest in the orexin space. And what I'm wondering is twofold. Number one, can you lay out timelines for indications beyond narcolepsy? Because I feel like that aspect of the value has not been captured by much of the valuation numbers that have been thrown around so far. And I ask that in particular because it seems like Lilly's early interest in Centessa was perhaps not even on the lead program.

嗨，各位，謝謝讓我提問。我有一個兩部分的問題。顯然市場對食慾素領域有非常多的興趣、策略性興趣。我想問兩點。第一，你們能否說明除了嗜睡症（narcolepsy）之外其他適應症的時間表？因為我覺得這部分的價值，迄今在外界拋出的許多估值數字中並沒有被充分反映。我特別這樣問，是因為看起來Lilly早期對Centessa的興趣，可能甚至不是在其主力計畫上。

And number two. More importantly, is Alkermes and the board open to the idea of asset sale rather than a whole company sale, if that were... were to be a possibility at any point. And I'm thinking back to examples like Biohaven. Thank you very much.

第二，更重要的是，如果在任何時間點存在這種可能性，Alkermes及董事會是否願意考慮「出售資產」而不是「出售整家公司」的想法？我想到像Biohaven那樣的案例。非常感謝。

Umer, maybe I'll start, and then I'll hand over to Blair as well. Yes, I think Blair just referred to it in the prepared comments, which is the two most immediate adjacencies to the hypersomnolence are fatigue and ADHD.

Umer，也許我先回答，然後再交給Blair補充。是的，我想Blair在事先準備的評論中也提到：在過度嗜睡（hypersomnolence）之外，最直接相鄰的兩個方向是疲勞與ADHD。

We're enrolling patients right now in the first ADHD study, that translational study in adult patients. So that'll be a 50-patient study. We'll get data this year on ADHD. So give us our first sense. And we won't even wait for those data before we light off a bigger, proper Phase II program, which we'll light off this summer in ADHD, because we feel like the preclinical evidence in that space is quite compelling.

我們目前正在招募第一項ADHD研究的受試者，那是一項在成人患者中的轉譯研究。因此那會是一項50名患者的研究。我們今年會拿到ADHD的數據，讓我們得到第一個初步判讀。而且我們甚至不會等到那些數據出來才啟動更大型、正式的第二期（Phase II）計畫；我們會在今年夏天於ADHD啟動，因為我們認為該領域的臨床前證據相當有說服力。

And the enrollment in the fatigue studies in Parkinson's and whatever, MS that starts this year as well. So we're right on the threshold of new data sets that expand the understanding of the pharmacology in patients without demonstrable orexin deficits. And as the first hints of that come from our NT2 data and our IH data that we've already developed.

此外，帕金森氏症疲勞以及（還有）MS的疲勞研究也會在今年開始招募。因此我們正站在一個門檻上，即將出現新的數據集，擴大我們對於在沒有可證實食慾素缺乏的患者中之藥理作用的理解。而這方面的第一些線索，已經從我們已完成的NT2數據與IH數據中開始浮現。

So, with regard to the second question, our company and our board, we're a public company, we react to whatever circumstances present themselves, but we feel like right now we're right on the threshold of major valuation changes as we mature this program. And I think Lilly coming into the market underscores the fact that there's more than just hypersomnolence here at play. This circuitry is directly associated with human wakefulness defined broadly, and I think that opens up a whole bunch of adjacency. And we start with hypersomnolence and we go from there. Blair, any other thoughts?

所以，關於第二個問題，我們公司與董事會作為一家上市公司，會對任何出現的情況作出反應；但我們認為，就目前而言，隨著我們把這個計畫推進成熟，我們正處於估值可能出現重大變化的門檻上。我認為Lilly進入市場也凸顯了一點：這裡不只是過度嗜睡在發揮作用。這套神經迴路與人類清醒狀態（以廣義定義）直接相關，我想這會打開一整串相鄰適應症的機會。我們從過度嗜睡開始，然後再往外延伸。Blair，還有其他想法嗎？

No, I'd just reiterate what Rich said, which is we're in a process right now. We're going to be turning over a lot of cards with regards to a number of these clinical areas. And we're looking to really execute and drive value over the next couple of years. So I think it's a little premature to talk about any potential sale process.

沒有，我只是重申Rich所說的：我們目前正處於一個過程中，會在多個臨床領域翻開很多牌。我們希望在未來幾年真正把執行做好並推動價值。因此我認為現在談任何潛在的出售流程都還有點太早。

Paul Mateus, Stifel.

Paul Mateus，Stifel。

Hey, this is Julian on for Paul. Thanks so much for taking our questions. And I guess just to piggyback again on the orexin program and the pipeline, it would be great to hear about for this larger Phase II that you're kicking off this summer, what types of patients are you hoping to enroll, and can you just talk a little bit about the translatability of what you'd expect based on past clinical data literature in terms of success on the primary endpoint and how may that translate to a larger randomized Phase III. And I guess in comparison, how large are Phase III studies relative to the Phase II that you plan on kicking off? Thanks.

嗨，我是Julian，代Paul提問。非常感謝回答我們的問題。我想再延伸一下食慾素計畫與產品線：對於你們今年夏天要啟動的較大型第二期研究，你們希望納入哪些類型的患者？另外，能否談談基於既有臨床數據文獻，你們對主要終點成功的可轉譯性預期，以及這可能如何轉化到更大型、隨機分派的第三期（Phase III）？還有相較之下，第三期研究的規模通常相對於你們計畫啟動的第二期會有多大？謝謝。

Yeah, thanks for the question. I think with regards to the ADHD, as I said earlier in the call, we saw pretty broad activity in some of our early models with regards to this asset and this mechanism. And so as we look to enroll our patients in the phase II study, we think a broad base of patients will be beneficial from this. So we're not going to look at individual subtypes. Our key primary endpoint for this is the [ACERS], which is the adult tool that's been used widely in industry. And what we're really looking to do is see the relative effect size across the patient population.

好的，謝謝你的問題。關於ADHD，如同我在電話會議前面提到的，我們在一些早期模型中，針對這個資產與機制看到了相當廣泛的活性。因此在第二期研究的收案上，我們認為廣泛的患者基礎都可能受益。所以我們不會去鎖定個別亞型。我們的關鍵主要終點是[ACERS]，這是業界廣泛使用的成人評估工具。我們真正想做的是觀察在整體患者族群中的相對效果量（effect size）。

And just to give an idea of what people have seen in the past, there's typically, it kind of breaks into two main areas. You typically see the non-stimulants and they typically have cone effect sizes that are kind of 0.3 to 0.45 or so, and then what you see is a very different result with stimulants.

為了讓大家了解過去的結果，通常大致可分成兩個主要區塊：你通常會看到非興奮劑（non-stimulants），其Cohen效果量一般大約在0.3到0.45左右；而興奮劑（stimulants）則會呈現非常不同的結果。

Typically can be one and above with regards to Cohen Z, but it comes with trade-offs. And so what we're really looking to see is how we perform on that over a four-week period. That study, as we said in the prepared remarks, is going to be about 300 patients. And that's roughly the size that you see in some of the phase III programs. And you go a little longer. Usually you're looking at six plus weeks on the primary endpoint. But we'll determine that and we'll indicate more of that after we see the data in the phase two.

就Cohen Z而言，通常可以到1或以上，但也伴隨取捨。因此我們真正想看的，是在四週期間我們在這方面的表現。如同我們在事先準備的說明中提到，該研究大約會有300名患者。這大致就是你在某些第三期計畫中看到的規模。只是第三期會做得更久，通常主要終點會看六週以上。不過我們會在看到第二期數據後再做決定，並提供更多說明。

I just want to add a couple things on that. Number one, what we did in narcolepsy is what we want to do in ADHD, that is have a significant amount of clinical data before we launch the Phase III program and run a Phase II program that almost mimics a Phase III program. That's a major risk mitigator in the program. Second thing is we're going to start using the tools that exist, just like we did in narcolepsy. But what's interesting about this pathway is that it's activating the brain in different ways than a stimulant activates the brain. And I think with the benefit of additional clinical data, we'll be able to dial into some of the differential efficacy potential of an orexin agonist compared to just a stimulus, which is revving up the brain in a more general way.

我想再補充兩點。第一，我們在嗜睡症所做的，就是我們想在ADHD複製的做法：在啟動第三期計畫之前先累積相當多的臨床數據，並執行一個幾乎模擬第三期的第二期計畫。這能大幅降低計畫風險。第二，我們會先使用既有工具，就像我們在嗜睡症所做的一樣。但這條路徑有趣之處在於，它以不同於興奮劑的方式活化大腦。我認為，隨著更多臨床數據的累積，我們將能更精準地掌握食慾素致效劑相較於單純刺激物（stimulus）——也就是以更一般性的方式把大腦「催上去」——在差異化療效上的潛力。

Thanks so much. And sorry, just one quick question, if I may as well. I think you said you'd be completing the IH study in 4Q, Rich, are we expecting data this year or could it potentially run into next year? Thanks.

非常感謝。也抱歉，如果可以的話我再快速問一個問題。我想你剛才說你們會在第四季完成 IH 研究，Rich，我們預期今年會有數據嗎？還是有可能延到明年？謝謝。

That's the translational study, the first study where we're looking at more -- IH. Oh, I'm sorry. IH. I'm sorry. Yeah, the IH orexin study, we'll complete that in Q4, and we'll get the data as fast as we can thereafter. It could be right at the end of the quarter or right at the beginning of the second quarter, according to the current plan.

那是轉譯研究，也就是我們第一個在看更——IH 的研究。噢，抱歉。IH。不好意思。對，IH 的 orexin 研究，我們會在第四季完成，之後會盡快取得數據。依照目前計畫，可能會在該季的最後，或是在第二季一開始。

Thanks for the clarification.

謝謝你的澄清。

Jessica Fye, JPMorgan.

Jessica Fye，摩根大通。

Great. Good morning. Thanks for taking my question. Just a question on LUMRYZ and your guidance for that product this year. Can you just talk about what's embedded as it relates to your expectation for any potential net price pressure as non-AG generic sodium oxabate, gains traction in the marketplace.

很好。早安。謝謝讓我提問。我想問一下 LUMRYZ 以及你們今年對這個產品的指引。能否談談你們的預期中，是否已納入非 AG 的學名藥 sodium oxabate 在市場上取得進展後，可能帶來的任何淨價格壓力？

Yeah, sure, I'll take that one. So at this point right now, as I stated, we're guiding to $350 million to $370 million. We had a really solid first quarter, and so we feel really good about that heading into Q2 and for the remainder of the year. At this point, we haven't seen any impact on multi-source generics for XYREM. Again, the most important point is this is a multi-source generic for XYREM, not for LUMRYZ. So we haven't seen any impact on demand, any impact on physician behavior, any change in payer behavior at this point.

好的，當然，我來回答。目前如我所說，我們的指引是 3.5 億到 3.7 億美元。我們第一季表現非常穩健，因此對進入第二季以及今年剩餘期間都很有信心。就目前而言，我們尚未看到多來源學名藥對 XYREM 造成任何影響。再次強調，最重要的一點是，這是針對 XYREM 的多來源學名藥，而不是針對 LUMRYZ。因此到目前為止，我們沒有看到需求受到影響、沒有看到醫師行為受到影響，也沒有看到付款方行為有任何改變。

A really solid part about the LUMRYZ story is really the diverse patient mix. We get a sizable portion of patients from nutoxabate. From returning oxavate and from the switch market. So it's a very durable product. So it's something that we're watching very closely. We're going to have to see how it plays out. But with our full-year guide, we do incorporate a range of gross-to-net scenarios.

LUMRYZ 故事中一個非常扎實的部分，是病患組合相當多元。我們有相當比例的病患來自 nutoxabate、來自回流的 oxavate，以及來自轉換市場。因此這是一個非常耐久的產品。我們會非常密切地觀察，接下來要看市場如何發展。不過在我們的全年指引中，確實已納入一系列的毛利到淨額（gross-to-net）情境。

Ben Burnett, Wells Fargo.

Ben Burnett，富國銀行。

I wanted to ask about the Vibrance III data that you will provide in the fourth quarter or thereabouts. I guess, what dose cohorts will be included in the update? And will this include split dosing at therapeutically relevant doses?

我想問一下你們將在第四季左右提供的 Vibrance III 數據。我想了解，更新中會包含哪些劑量隊列？以及是否會包含在具治療相關劑量下的分次給藥？

Yeah. We expect to have top-line results from the entire study when we read out the data from that, which would include the split-dose arm.

是的。我們預期在公布數據時會提供整個研究的主要（top-line）結果，其中會包含分次給藥組。

Okay. Fantastic. And can I ask, the split dosing that's being tested, how is that split? Are they evenly split? And are you testing sort of higher total doses in the split dosing cohorts relative to the single dose cohorts?

好的。太好了。我可以再問一下，正在測試的分次給藥是怎麼分的？是平均分配嗎？另外，你們在分次給藥隊列中測試的總劑量，是否會高於單次給藥隊列？

We haven't disclosed the specifics on the split dose strategy either for the IH study or for the other studies as well, partly because we feel like we've learned so much from our clinical program that is proprietary that we're going to keep that close to our vest until we have the data.

我們尚未披露分次給藥策略的具體細節，不論是 IH 研究或其他研究也是如此，部分原因是我們覺得從臨床計畫中學到很多屬於專有的內容，因此在拿到數據之前，我們會先保留不公開。

Marc Goodman, Leerink Partners.

Marc Goodman，Leerink Partners。

Yes. On LUMRYZ, can you talk about the net patient starts that got you through the 3,600 patients that ended the quarter? And then now that you own the asset, can you give us an update of how you plan to develop Valiloxybate ?

是的。關於 LUMRYZ，你能談談推動你們在季末達到 3,600 名治療中病患的淨新增起始用藥人數嗎？另外，現在你們已擁有該資產，能否更新一下你們打算如何開發 Valiloxybate？

Yes. Hey, Mark, I'll take the first part of that. So overall, as I said in my prepared remarks, the brand in Q1 realized 3,600 patients on therapy. We actually think that total patients on therapy is the best metric. That's a 28% year-over-year growth overall. That's really the durable part of the brand. That really incorporates any type of demand perspective access and also persistency.

好的。嗨，Mark，我先回答第一部分。整體而言，如我在事先準備的發言中所說，該品牌在第一季達到 3,600 名正在接受治療的病患。我們其實認為「治療中病患總數」是最好的指標。這代表整體年增 28%。這正是品牌最具耐久性的部分，因為它涵蓋了需求面、可近性（access）以及持續用藥（persistency）等各種面向。

So our focus is really on total patients. We're always going to be focused moving forward on growing net patient adds. And we feel really good about the enrollment trends we saw coming at the end of the quarter, which is going to set us up very well for Q2 and beyond. And that's really based upon just the overall strength of the mix between new to Oxybate switch and also returning, so we feel good about the patient mix that we're seeing.

因此我們的重點確實放在治療中病患總數。我們未來也會持續聚焦於提升淨新增病患數。我們對於季末看到的入組趨勢感到非常樂觀，這將讓我們在第二季及之後有很好的起跑點。而這主要是基於「新用 oxybate、轉換，以及回流」之間整體組合的強勁表現，所以我們對目前看到的病患組合感到滿意。

And hey, Mark, this is Blair. I'll take the Valiloxybate question. So that's an asset that came over as part of the Avadel acquisition, and that's an opportunity for us to potentially develop a no-salt, once-nightly product for patients. And so our plan for that is to take multiple formulations into the clinic and really try to assess a rapid development program. And this is really right up our wheelhouse, as you know. Formulation company at our roots, and especially when it comes to PK/PD relationships. So we right now have multiple formulations that are in the clinic and being assessed. And as we have more data later in the year, we'll share that.

嗨，Mark，我是 Blair。我來回答 Valiloxybate 的問題。這是一項隨 Avadel 併購案一併納入的資產，對我們而言是一個潛在機會，可為病患開發一款無鹽、每晚一次的產品。我們的計畫是把多種配方帶入臨床，並嘗試評估一個快速的開發方案。這也正是我們的強項，如你所知，我們本質上是一家配方公司，尤其在 PK/PD 關係方面。目前我們有多種配方正在臨床中評估。等到今年稍晚有更多數據時，我們會再分享。

Blair, do you think you're going to have to do a full, like a full Phase III study, or will you be able to do like some type of bridging study that is quicker?

Blair，你覺得你們需要做完整的第三期試驗嗎？還是可以做某種更快的橋接研究？

Well, that'll really depend on the clinical data that we generate. So our hope is that we can do some bridging, but again, we'll have to see how this asset performs in the clinic.

這真的要看我們產生的臨床數據而定。我們希望能做一些橋接，但同樣地，我們得先看看這個資產在臨床上的表現。

Rudy Li, Wolfe Research.

Rudy Li，Wolfe Research。

Thanks for taking my question. Can you talk about your current understanding of the competitive landscape for orexin agonist? And specifically, what key endpoints being measured in your breeding phase 3 trial that could provide additional label differentiation? Thanks

謝謝讓我提問。你能談談你們目前對 orexin 促效劑競爭態勢的理解嗎？特別是，你們在關鍵性第三期試驗中衡量哪些關鍵終點，可能帶來額外的標籤差異化？謝謝。

I think the major differentiating feature in the erection space now is the fact that Alkermes has the only program that has a range of doses. That have been credentialed in large randomized phase two studies. And in so doing, we've been able to explore other domains other than just the classic maintenance of wakefulness test and the cataplexy scale by extending into fatigue and cognition.

我認為目前在 orexin 領域最主要的差異化特徵，是 Alkermes 擁有唯一一個涵蓋一系列劑量的計畫，而且這些劑量已在大型隨機第二期研究中獲得驗證。透過這樣的設計，我們得以探索不僅是傳統的清醒維持測試（maintenance of wakefulness test）與猝倒量表（cataplexy scale），也延伸到疲勞與認知等其他面向。

So while we don't expect fatigue and cognition data to be in our initial label, what we do expect is have a clinical data set that encompasses all those features of the treatment. So when we come to market, if the drug is approved, we expect to come to market for NT1 and NT2. Which differentiates us from the first market entrant, as well as a range of doses across NT1 and NT2, both as once a day, as well as in split-dose formats, which further differentiates us from the first market entrant.

因此，雖然我們不預期疲勞與認知數據會出現在初始標籤中，但我們確實預期能擁有一套涵蓋治療各項特徵的臨床數據集。若藥物獲批，我們預期上市時將同時面向 NT1 與 NT2。這使我們有別於第一個進入市場的產品；此外，我們在 NT1 與 NT2 皆有一系列劑量，既可每日一次，也可採分次給藥形式，這也進一步讓我們與第一個進入市場的產品有所區隔。

And I think following the acquisition of Centessa, I think our lead in NT2, as well as NT1, continues to grow. So we're really happy with the competitive positioning, and we think this is going to open up the beginning of a brand-new class of pharmaceuticals that will continue to grow from the diseases of hypersomnolus.

另外，我認為在收購 Centessa 之後，我們在 NT2 以及 NT1 的領先幅度仍在擴大。因此我們對競爭定位非常滿意，也認為這將開啟一個全新藥物類別的起點，並將隨著嗜睡相關疾病的需求而持續成長。

Luke Herrmann, Baird.

Luke Herrmann，Baird。

Hi team, thanks for the question. One on 7,90 and ADHD, you laid out the effect sizes we've seen across different standards of care. So based on the preclinical data, do you think the more likely outcome as a monotherapy is sort of a more tolerable asset that sits in the middle of stimulants and non-stimulants in terms of efficacy? Or do you think efficacy could actually exceed what we've seen with stimulants?

各位好，謝謝讓我提問。第一個問題關於 7,90 與 ADHD，你們說明了在不同標準治療下我們看到的效應量。因此基於臨床前數據，你們認為作為單藥治療時，更可能的結果是：在療效上介於興奮劑與非興奮劑之間、但耐受性更好的資產？還是你們認為療效其實可能超過我們在興奮劑上看到的表現？

Well, again, what we've seen in our preclinical data is we performed as well or better than stimulants in our early models as monotherapy. So obviously, if we're able to achieve that clinically with the tolerability profile that we see with this class of drugs, that's a great outcome for us. But I think there's a wide range of market opportunities regardless of what we see in the clinic. But our goal will be to get the strongest efficacy possible.

嗯，再次強調，我們在臨床前數據中看到的是：作為單藥治療，在早期模型中我們的表現與興奮劑相當或更好。因此，若我們能在臨床上達到同樣效果，同時具備我們在這一類藥物上看到的耐受性特徵，對我們而言會是非常好的結果。不過我認為，不論臨床結果如何，市場機會的範圍都很廣。但我們的目標會是取得盡可能強的療效。

Great. And then just one follow-up on the alexorextin Phase III studies. I believe you commented on the high level of patient interest. Has this exceeded what you anticipated, and would this maybe lead to a more expeditious enrollment?

很好。接著再追問一個關於 alexorextin 第三期研究的問題。我記得你們提到病患興趣很高。這是否超出你們原先的預期？而這是否可能帶來更快速的入組？

The difference between Phase III and Phase II for us is that when you go into Phase 2, no one's used your drug before. And now we go into Phase 3 with a major data set that's been presented in major meetings and a buzz about this program what mitigates against the rate of enrollment, though, is the control and the rigor that we learned from Phase II about which sites to use and how to select patients and how to make sure that you're not just enrolling for the sake of enrollment numbers, but to enroll the finest cohort you can over the period, because those data become your label.

對我們而言，第三期與第二期的差異在於：進入第二期時，沒有人用過你的藥物。而現在我們進入第三期時，已經有一個在重要會議上發表過的大型資料集，且這個計畫也有一定的市場聲量。不過，可能抑制收案速度的因素，是我們從第二期學到的對照設計與嚴謹性——包括該使用哪些試驗中心、如何篩選病人，以及如何確保你不是為了收案數字而收案，而是在整個期間內收進你能收進的最佳受試者族群，因為那些資料會成為你的藥品標示（label）。

So the quality of that study is sacrosanct. So we expect to enroll the study correctly at the rate that we'll determine as we activate sites, and we'll keep you guys posted as we go on that.

因此，該研究的品質是神聖不可侵犯的。我們預期會在啟動各試驗中心的同時，以我們將決定的速度正確地完成收案，並且會在推進過程中持續向各位更新。

Joseph Thome, TD Cowen.

Joseph Thome，TD Cowen。

Hello, this is Jacob on for Joe. Thanks for taking my question. I was wondering if you were planning on studying LUMRYZ in combination with an OX2R agonist in the future, and if so, what would a trial for that look like?

你好，我是 Jacob，代替 Joe 提問。謝謝讓我提問。我想請教你們未來是否計畫研究 LUMRYZ 與 OX2R 致效劑（agonist）的併用；如果是，這樣的試驗會長什麼樣子？

Yeah, Jacob, it's something we're hearing so frequently from clinicians now that we've completed the acquisition. And we'll go to the sleep meeting in Baltimore representing both once nightly oxidate with extended efficacy as well as the alixorexton program. And so we will be harnessing that energy into a clinical program over time. We're not going to start that right away. We need to finish some other things first, namely the registration program for alixorexton as monotherapy. But I think there's increasing interest in understanding both the nighttime and the daytime aspects of the disease.

是的，Jacob，這是我們在完成併購後，現在非常頻繁從臨床醫師那裡聽到的想法。我們會到巴爾的摩的睡眠醫學年會，同時代表「每晚一次、具延長療效的 oxybate」以及 alixorexton 計畫。因此，我們會隨時間把這股動能轉化為臨床計畫。不過我們不會立刻啟動，因為我們需要先完成其他事項，尤其是 alixorexton 作為單一療法（monotherapy）的註冊性試驗計畫。但我認為，大家對於理解此疾病在夜間與日間兩個面向的興趣正在增加。

Ami Fadia, Needham and Company.

Ami Fadia，Needham and Company。

Good morning. Thanks for taking my question. I've got to -- just with regards to Vibrance II. That's going to be presented at the sleep meeting in Baltimore. What additional data on top of what you'd announced at the initial data readout that we can expect at the meeting?

早安，謝謝讓我提問。我想問一下——關於 Vibrance II。它將在巴爾的摩的睡眠年會上發表。相較於你們在初次數據讀出時已公布的內容，會議上我們還能期待看到哪些額外資料？

And with regards to the LUMRYZ study that's expected to read out in the second quarter, maybe talk about your expectations for what that profile is likely to look like, the market opportunity, and what you're doing in terms of preparing for a potential launch of that indication. Thank you.

另外，關於預計在第二季讀出的 LUMRYZ 研究，能否談談你們對其可能呈現之療效/安全性輪廓（profile）的預期、市場機會，以及你們在為該適應症可能上市所做的準備？謝謝。

Ami, it's Rich. I'll start. As I mentioned, we presented most all of the data on the Vibrance II study in November, and that's available on the website if people want to look at that again. But we will give a bit more sleep in two principal domains. One, we'll try to give a little bit more dimensionality to the efficacy effect that we saw. And the other is we do have data from the extension phase now that we can tack on to the double-blind phase. And that's always instructive to see what happens as patients stay on therapy for a longer period of time.

Ami，我是 Rich。我先回答。如我提到的，我們在 11 月已經發表了 Vibrance II 研究幾乎所有的資料；如果大家想再看一次，網站上也有。不過在睡眠年會上，我們會在兩個主要面向提供更多資訊：第一，我們會嘗試讓先前看到的療效效果更具「多維度」的呈現；第二，我們現在也有延伸期（extension phase）的資料，可以接在雙盲期（double-blind phase）之後一起呈現。這通常很有啟發性，因為可以看到病人在治療上維持更長時間後會發生什麼。

And of course, at the sleep meetings, those data are presented by investigators, and you have the ability to talk to people who are actually hands-on in the use of the drug.

當然，在睡眠年會上，這些資料是由研究者發表的，而你也能與實際第一線使用該藥物的人交流。

Your second question was about LUMRYZ in IH and the market opportunity for that. I'll start and then I'll ask Todd to comment on that. What's interesting is that the competitive product is iWave. The principal growth of that drug now is driven by the IH indication. And part of the reason we went into IH for olixarextin was as talking to patients and patient advocacy groups, there's a huge unmet need for new medicines in IH.

你的第二個問題是關於 LUMRYZ 在 IH（特發性嗜睡症）以及其市場機會。我先說，然後請 Todd 補充。有趣的是，競品是 iWave。該藥目前的主要成長動能來自 IH 適應症。我們之所以讓 olixarextin 進入 IH，部分原因是我們與病人及病友倡議團體交流後發現，IH 對新藥有非常巨大的未被滿足需求。

And we just had a thought leader here at the company yesterday saying that he thought Oxybates, at this moment, were probably the best treatment for idiopathic hypersomin, which is interesting. I think that's underappreciated. So we will be able to enter this market with LUMRYZ in 2028.

而且我們昨天才有一位思想領袖（thought leader）到公司，他表示他認為就目前而言，oxybate 類藥物可能是治療特發性嗜睡症最好的療法，這點很有意思，我覺得市場對此認知不足。因此，我們將能在 2028 年以 LUMRYZ 進入這個市場。

So we have some time to prepare for that type of launch if it's approvable. But we're quite excited about that as a life cycle growth tool for LUMRYZ, Todd.

所以，如果它具備可獲核准的條件，我們還有一些時間為這類上市做準備。但我們對此非常興奮，因為這會是 LUMRYZ 生命週期成長（life cycle growth）的工具之一。Todd？

Yes, I would just add a couple of things, we continue just to validate all of the research that we've done, listening to the community, listening to HCPs, we believe it's a really underdeveloped category right now. There's 40,000 patients that are diagnosed. We think that's underrepresented, and there's only one FDA-approved product on the market. We think that LUMRYZ has an opportunity to be the second product, and we know how well LUMRYZ is received in the community now for narcolepsy, so our expectations are very high on what the opportunity is for LUMRYZE and IH. As Rich said. As the data is presented, as we go through the approval process, we'll be continuing to build what our launch plan looks like, but it's something that we are very excited about.

是的，我再補充幾點：我們持續在驗證先前所做的研究——傾聽社群、傾聽醫療照護專業人員（HCPs）的聲音——我們相信這目前是一個開發不足的治療類別。已確診病人約 40,000 人，我們認為這個數字被低估了，而且市場上只有一個 FDA 核准的產品。我們認為 LUMRYZ 有機會成為第二個產品；同時我們也知道，LUMRYZ 目前在嗜睡症社群中的接受度非常高，因此我們對 LUMRYZ 在 IH 的機會抱持很高期待。正如 Rich 所說，隨著資料發表、以及我們走過核准流程，我們會持續完善上市計畫的樣貌；這也是我們非常期待的一件事。

Jason Gerberry, Bank of America.

Jason Gerberry，美國銀行（Bank of America）。

Hey, good morning. This is [Chiyon] on for Jason. Thanks for taking our question. I guess on ADHD, can you talk about what's the unique about the molecule PK or dosing profile. That could help you mitigate insomnia or urinary frequency, the class of adverse events you have observed in narcolepsy patients. And would you expect the ADHD patients to be more or less sensitive to these class AES so far?

嗨，早安。我是 [Chiyon]，代替 Jason 提問。謝謝讓我們提問。我想就 ADHD 請教：你們能否談談這個分子在藥物動力學（PK）或給藥/劑量設計上有何獨特之處，能幫助你們降低失眠或尿頻——也就是你們在嗜睡症病人中觀察到的那一類不良事件？另外，就目前所知，你們預期 ADHD 病人對這類不良事件（class AEs）的敏感度會更高還是更低？

And just a quick follow-up on vibrance too. Would you provide any sort of kinetics on weekly MWT data to better contextualize data comparison relative to a key competitor of yours, which had two-week data. You've talked about observation of tachyphylaxis in the past with Vibrance 2. Thanks.

另外快速追問 Vibrance II：你們是否會提供每週 MWT 數據的某種動態/時間變化（kinetics），以便更好地將你們的資料與某個主要競品（其資料是兩週）做對照？你們過去曾談到在 Vibrance 2 觀察到速效耐受（tachyphylaxis）。謝謝。

All right, [Chi], it's Blair. I'll start with the ADHD and then I'll get Rich to answer you on the Vibrance II stuff. So with regards to ADHD, I think a couple of things I want to make sure we're clear on. One is the adverse events that we typically see with this class of arrested agonists.

好的，[Chi]，我是 Blair。我先回答 ADHD，然後請 Rich 回答你 Vibrance II 的部分。關於 ADHD，我想先釐清幾點。第一，是我們通常在這一類受體致效劑（agonists）中看到的不良事件。

It's a very wide therapeutic window. As you saw from our programs in NT1 and NT2, we have a really nice AES profile overall. There's. The main effects associated with this class are really polykorrhea and some transient insomnia that we see at the beginning of the study.

它的治療窗非常寬。從我們在 NT1 與 NT2 的計畫你也看到，我們整體的不良事件（AE）輪廓相當不錯。這一類藥物主要相關的影響，主要是多尿（polyuria）以及在研究初期看到的一些短暫性失眠。

As we talk about the ADHD program and the PK dosing profile, I think with regards to any of the new programs that we move outside of narcolepsy. We're developing them with new drugs. So ALKS 7290 is its own unique molecule. It's been designed by itself specifically. It's optimized for the patient populations that we're going after.

談到 ADHD 計畫與 PK/劑量設計，我認為對於任何我們從嗜睡症延伸到其他適應症的新計畫，我們都是以新藥來開發。因此 ALKS 7290 是一個獨特的分子，是專門獨立設計的；它已針對我們要切入的病人族群做最佳化。

And so it'll have its own unique PK and dosing profile that will match that patient population. As what we saw in our NT2 program is that patients who have an intact orexin system, so who have natural orexin tone, we tend to see a very mitigated.

因此，它會有自己獨特的 PK 與給藥/劑量輪廓，以符合該病人族群。我們在 NT2 計畫中看到的是：對於食慾素（orexin）系統完整、也就是具有自然食慾素張力（orexin tone）的病人，我們通常會看到相當被緩解的——

Overall AE profiles due to that fact. And so, again, I think we're well positioned to test a wide range of doses within that patient class.

整體 AE 輪廓，正是因為這個因素。因此，再次強調，我們很有條件在該病人族群中測試相當寬的劑量範圍。

Rich, do you want to do?

Rich，你要回答嗎？

Yeah, the Vibrance II data at sleep, you will see time course data on a multi-week basis for the ESS score. And I just want to make the point that there is no competitive data that's been presented so far. There's only one company that's shown multi-week successful data in NT2, and that's Alkermes.

好的。關於睡眠年會上的 Vibrance II 資料，你會看到以多週為基礎的 ESS 分數時間序列資料。我也想強調一點：目前為止並沒有任何競品資料被發表。到目前為止，只有一家公司在 NT2 顯示多週且成功的資料，那就是 Alkermes。

Akash Tewari, Jefferies.

Akash Tewari，Jefferies。

Hi, this is Anastasia on for Akash. Thanks for taking the question. So when you previously talked about NT2, you've kind of segmented the pop into a couple buckets of patients. You have the ones who would benefit from bid dosing and then the ones with kind of a more modest effect size. So how are you thinking about that dynamic as you consider orexins working in other indications where patients have more normal hypercretin levels at baseline, like, ADHD or fatigue?

嗨，我是 Anastasia，代替 Akash 提問。謝謝讓我提問。你們先前談到 NT2 時，曾把族群大致分成幾個病人「桶」：有些人會受益於每日兩次（BID）給藥，另一些人的效果幅度較為溫和。那麼，當你們考慮把食慾素（orexin）機制用在其他適應症時——例如 ADHD 或疲勞——而這些病人在基線時的 hypocretin（食慾素）水平更接近正常，你們如何看待這種動態？

We just think overall dosing flexibility. Will be a really important thing, because people have different physiologic set points for their base orexin tone, and they have different lifestyle expectations, whether they want to stay up till 10 o 'clock at night, or they want to go to bed at 7 PM so our feeling is that we've established in data so far in T2 patients, as well as IH in early stage, that patients with normal orexin tones can benefit from an orexin agonist. So then that degree of that benefit will be determined by.

我們認為整體而言，劑量彈性會非常重要，因為每個人的基礎食慾素張力（orexin tone）在生理上有不同的設定點（set point），而且生活型態期待也不同——有人想晚上 10 點才睡，也有人想晚上 7 點就上床。因此，我們的看法是：截至目前在 T2 病人，以及早期 IH 的資料中，我們已經建立了證據，顯示具有正常食慾素張力的病人也能從食慾素致效劑中受益。接下來，受益的程度將取決於——

Each individual's set point as I just described. So the prerequisite for addressing that commercially is just a range of doses with data supporting that range of doses in the label, which is exactly why we've designed the pivotal study, the brilliant study, to include once-daily dosing, split dosing across that range of doses that we elaborated in Phase II.

如我剛才所描述的，每位個體都有其各自的設定點。因此，要在商業上解決這個問題的前提，就是在標籤上提供一個有數據支持的劑量範圍，而這也正是我們設計關鍵性研究（這項出色的研究）的原因：納入每日一次給藥，以及在我們於第二期試驗中闡述的該劑量範圍內進行分次給藥。

Ash Verma, UBS.

Ash Verma，瑞銀（UBS）。

Hi, this is [Hu Youn] on for ASH. Thanks for taking our questions. Our first question is for the pending LUMRYZ IH study. How do you think about the placebo arm here, given the patients may have some bias knowing that sodium oxabine works in IH?

大家好，我是代表 ASH 的 [Hu Youn]。感謝讓我們提問。我們的第一個問題是關於即將進行的 LUMRYZ IH 研究。鑑於患者可能因為知道氧巴酸鈉在 IH 中有效而產生某種偏差，您如何看待此處的安慰劑組設計？

And our second question is, so it's good to see the decent beat on Vivitrol. Can you help us understand your latest thoughts on how the Vivitrol revenue trajectory could be in 2027 and beyond as Teva's generic enters? Thank you.

第二個問題是，很高興看到 Vivitrol 的表現明顯優於預期。能否協助我們理解，隨著 Teva 的學名藥進入市場後，您對 2027 年及之後 Vivitrol 營收走勢的最新看法？謝謝。

I'll take the first, and Blair and Todd talk about the second. Just understand the LUMRYZ IH phase three study is a randomized withdrawal study. So patients would have all been on the Oxybate. So they'll know there's no blinding issue, and then it's withdrawn on a blinded basis. So this is the same design that Jaz used with their XY study.

我先回答第一個，Blair 和 Todd 會談第二個。請理解，LUMRYZ IH 第三期研究是一項隨機撤藥研究。因此，患者一開始都會使用氧巴酸鹽（oxybate）。所以他們會知道不存在盲法問題，接著在盲態下撤除用藥。這與 Jazz 在其 XY 研究中採用的是相同設計。

Yeah, and I think with regards to Vivitrol, as we move into 2027, there's a number of interesting scenarios in front of us. Obviously, we have the potential entrant of Teva into the space in the beginning of 2027. And we're looking at a lot of scenarios related to that, including some scenarios where Teva actually isn't able to make it into market. What we don't expect though is to have a really dramatic impact on Vivitrol as the new entrant comes into the place. Vivitrol is a unique asset, it requires a lot of manufacturing capability, it requires a lot of commercial infrastructure and hand-holding with patients and physicians. And Todd can give you a little more on that.

是的，至於 Vivitrol，當我們邁入 2027 年時，面前有幾種有意思的情境。顯然，Teva 可能在 2027 年初進入這個領域。我們正在評估許多相關情境，包括某些情境下 Teva 實際上無法成功上市。不過，我們不預期新進者進入後會對 Vivitrol 造成非常劇烈的影響。Vivitrol 是一項獨特資產，它需要很強的製造能力，也需要大量的商業基礎設施，以及對患者與醫師的密切支持與指導。Todd 可以再補充一些。

Yes, absolutely. Just to kind of reiterate, we have really two key priorities right now, and that's delivering for 2026 for Vivitrol. We're right on track to be in the range of our full year guidance, really driven by the alcohol dependence indication. And to reinforce what Blair said, we've been working on this for a number of years. We have a.

是的，完全同意。再重申一下，我們目前確實有兩個關鍵優先事項，其中之一就是為 2026 年的 Vivitrol 交付成果。我們正按計畫推進，預期可落在全年財測指引區間內，主要由酒精依賴適應症所帶動。並且如 Blair 所說，我們已經為此投入了好幾年。我們有一個。

A range of scenarios that we're playing through, and our research continues to reinforce that we don't see this as a typical erosion. If Teva were to make it into the market, it's a durable product.

我們正在推演一系列情境，而我們的研究持續強化一點：我們不認為這會是典型的侵蝕（erosion）。即使 Teva 真的進入市場，這仍是一個具耐久性的產品。

And so we'll be prepared regardless of what those scenarios are to flex our resources if we need to and also be prepared to compete.

因此，無論最終是哪種情境，我們都會做好準備；如有需要，我們也會調整資源配置，並且準備好參與競爭。

Uy Ear, Mizuho Securities.

Uy Ear，瑞穗證券（Mizuho Securities）。

Hey guys, thanks for taking your questions. So maybe, apologies for missing as I dialed in a little bit late. Could you maybe just help us understand if there's a reason or not on why the patient mix may change going through the year, given the nice patient mix that led to better than expected gross in that. And the second question is, on ADHD, is there anything else in terms of potential differentiation other than efficacy? Thanks.

各位好，感謝回答問題。可能先說聲抱歉，我撥入稍微晚了一點，可能漏聽了一些。能否協助我們理解，為什麼患者組合在一年當中可能會改變或不會改變？因為第一季的患者組合不錯，帶來了優於預期的毛利表現。第二個問題是，關於 ADHD，除了療效之外，還有沒有其他潛在差異化因素？謝謝。

Yeah, I'll take the first one regarding patient mix. Patient mix, we did see some favorability, some Medicaid favorability in the first quarter of the year. We don't expect -- we don't actually forecast on favorable patient mix. We do expect that for the full year that we would see the access profile for Libalvi. So we do have better line of sight to what that profile would look like, we're always in active negotiations with payers and our full year range actually assumes that that could play through.

好的，我先回答患者組合的問題。第一季我們確實看到一些有利因素，例如 Medicaid（醫療補助）占比相對有利。我們不會把「有利的患者組合」納入預測；我們對全年預期是會呈現 Libalvi 的可及性（access）輪廓。因此，我們對該輪廓會長什麼樣子有更清晰的能見度；我們也一直在與付款方積極談判，而我們的全年區間其實也假設這些因素可能會在過程中發生。

But that's the real logistics of the business right now, we're just not forecasting any additional favorability for the remainder of the year.

但就目前業務的實際運作而言，我們並未預測今年剩餘期間還會出現額外的有利因素。

And then with regards to ADHD, look, we're looking for differentiation both on efficacy and tolerability. I think if you look at the ADHD market and how it's evolved, it really was started around the stimulants and the amphetamine use within adults and children. And that comes with significant trade-offs. It comes with side effects. It comes with potential abuse.

至於 ADHD，我們尋求的差異化同時包括療效與耐受性。我想如果你看 ADHD 市場及其演變，最初主要是以興奮劑為主，包含成人與兒童使用安非他命類藥物。而這伴隨著顯著的取捨：會有副作用，也存在潛在濫用風險。

And I think people have been really looking for more tolerable agents that are maybe non-stimulant for a long time. And up until now, really the efficacy of those agents really just hasn't matched what you've seen in the stimulant class. So I think the really holy grail for this indication in this area is to create an asset that has.

我認為長期以來，人們一直在尋找更具耐受性、可能是非興奮劑的藥物。但直到目前為止，這些藥物的療效確實還無法匹配你在興奮劑類別中看到的效果。因此，我認為在這個適應症領域真正的「聖杯」，是打造一個資產，能夠同時具備。

The efficacy of a Vyvanse or something like that, but also is really well tolerable. And the orexin agonist class has the potential for that. It's a new mechanism of action. It operates on the alertness centers in the brain. We've seen attention and impulsivity benefits in preclinical models.

像 Vyvanse 或類似藥物那樣的療效，但同時又具有非常好的耐受性。而食慾素（orexin）致效劑（agonist）類別具備這種潛力。這是一種新的作用機轉，作用於大腦的覺醒中樞。我們在臨床前模型中看到注意力與衝動控制方面的益處。

We've seen the right neurotransmitter release and profile as we look at these assets. So we think there's a real opportunity here to really thread that needle. And provide a new benefit to this patient population.

在評估這些資產時，我們也看到符合預期的神經傳導物質釋放與特徵。因此，我們認為這裡確實存在機會，能夠真正兼顧兩者，並為這個患者族群帶來新的益處。

David Hong, Deutsche Bank.

David Hong，德意志銀行（Deutsche Bank）。

Hi, there. Thanks for fitting me in and taking my questions. So I said two, maybe first with the Vibrance-3 IH study. When we do get that data for the split dosing arm, I guess, ideally, what would you like to see for that split dose versus a single dose to help validate your hypothesis? And I guess, do you just have any sense of in the real-world setting if a split dose or a single dose would be preferred?

您好，謝謝讓我加入並回答我的問題。我有兩個問題。第一個是關於 Vibrance-3 IH 研究：當我們拿到分次給藥組的數據時，理想情況下，您希望看到分次劑量相對於單次劑量呈現什麼結果，以幫助驗證你們的假設？另外，在真實世界情境中，您是否覺得分次給藥或單次給藥會更受偏好？

And then on the alum rise opportunity in IH. If LUMRYZ is approved for IH, how do you think about where your patients may come from? Do you think that would be mostly oxidate-naive in IH? Or would you think that there would be a good proportion of switches from XiWave as well? Thanks a lot.

第二個是關於 LUMRYZ 在 IH 的機會：如果 LUMRYZ 獲批用於 IH，您如何看待患者來源？您認為主要會是 IH 中未使用過氧巴酸鹽（oxybate-naive）的新患者嗎？還是您認為也會有相當比例會從 XiWave 轉換過來？非常感謝。

Hey, David. It's Rich. I'll take the first. The hypothesis for the split dose in IH is driven by the observations that we saw in the NT2 study. And so the simple readout would be to look at the MWT. And see whether we're extending the later time points and elevating the latencies of the later time points. Recognizing that it's almost a laboratory measure that we're using in the IH population because the MW2 is not a preferred endpoint for IH, but it's simply a way for us to demonstrate the pharmacodynamic effect of the split dose and to confirm our dosing assumptions.

David 你好，我是 Rich。我先回答第一個。IH 中分次給藥的假設，來自我們在 NT2 研究中觀察到的結果。因此，最直接的讀法是看 MWT，並觀察我們是否延長較後面時間點、並提高較後面時間點的入睡潛伏期（latency）。需要指出的是，我們在 IH 人群中使用 MWT 幾乎算是一種實驗室量測，因為 MWT 並不是 IH 的首選終點；但它只是用來展示分次給藥的藥效動力學（pharmacodynamic）效應，並確認我們的給藥假設。

In the real world, we've talked to a lot of different folks in the course of market research. I think that the once daily will continue to be probably the modal approach that patients use. But over time, as the category continues to mature, I think we analogize it to the ADHD space, where there's a whole range of dosing alternatives, and people can tailor their dose to their lifestyle. And that's why we think there will be a real virtue to having a suite of once-daily doses, as well as accompanying split doses that people can then dial in to the level of wakefulness that matches their lifestyle and their disease.

在真實世界方面，我們在市場調研過程中與許多不同人士交流。我認為每日一次給藥可能仍會是患者最常採用的方式。但隨著這個類別逐步成熟，我們會把它類比到 ADHD 領域：那裡有一整套不同的給藥選項，人們可以依生活型態調整劑量。這也是為什麼我們認為，提供一系列每日一次劑量，以及相應的分次劑量，會有很大的價值，讓人們能把覺醒程度調整到符合其生活型態與疾病狀況的水平。

Yeah, and in terms of the IH opportunity for LUMRYZ, we clearly see a high unmet need here. We think there's a significant opportunity for expansion potential, because we think that the market right now is very modest. Even with that one product approved, there's only a very modest penetration. So we see market expansion opportunity, which will be a new patient start opportunity. That Lumarize will have the ability to tap into. That's what we've seen with narcolepsy. But at the same time, it's also going to create another market, which is a switch market. And that's what we've seen with narcolepsy. So we think that it will mimic kind of the patient patterns that we've seen in narcolepsy, which is new to oxybate patients, switch patients, and returning patients.

是的，至於 LUMRYZ 在 IH 的機會，我們清楚看到這裡存在高度未被滿足的需求。我們認為有顯著的擴張機會，因為目前市場規模很小。即使已有一個產品獲批，滲透率也仍然非常有限。因此，我們看到市場擴張的機會，也就是新患者起始治療的機會，LUMRYZ 將能夠切入。我們在嗜睡症（narcolepsy）中也看到過這種情況。但同時，它也會形成另一個市場，也就是轉換市場（switch market）。這同樣是我們在嗜睡症中看到的。因此我們認為，它會模擬我們在嗜睡症中看到的患者模式：氧巴酸鹽新用戶、轉換患者，以及回流患者。

And this now concludes our question-and-answer session. I would like to turn the floor back over to Sandra Coombs for closing comments.

現在問答環節到此結束。我想把時間交回給 Sandra Coombs 作結語。

Great. Thank you, everyone, for joining us on the call today. Please don't hesitate to reach out to us at the company if we can be further helpful. Thank you.

很好。感謝各位今天參與電話會議。如我們還能提供進一步協助，請隨時與公司聯繫。謝謝。

Ladies and gentlemen, thank you for your participation. This does conclude today's teleconference. You may disconnect your lines and have a wonderful day.

各位女士、先生，感謝您的參與。今天的電話會議到此結束。您可以掛斷電話，祝您有美好的一天。