Neurocrine Biosciences Inc (NBIX) 2025 Q1 法說會逐字稿

Good day, everyone, and welcome to Neurocrine Biosciences reports first quarter 2025 results. (Operator Instructions) Please note, today's call will be recorded. (Operator Instructions) It is now my pleasure to turn the conference over to Todd Tushla, Vice President of Investor Relations. Please go ahead.

大家好，歡迎閱讀 Neurocrine Biosciences 2025 年第一季業績報告。（操作員指示）請注意，今天的通話將會被錄音。（操作員指示）現在我很高興將會議交給投資者關係副總裁 Todd Tushla。請繼續。

Thank you, and happy Cinco de Mayo to everyone. Welcome to Neurocrine Biosciences first quarter 2025 earnings call. With me today are Kyle Gano, Chief Executive Officer; Matt Abernethy, Chief Financial Officer; Eric Benevich, Chief Commercial Officer; and for one last time as Chief Medical Officer, Eiry Roberts.

謝謝大家，祝大家五月五日節快樂。歡迎參加 Neurocrine Biosciences 2025 年第一季財報電話會議。今天與我一起出席的有執行長 Kyle Gano、財務長 Matt Abernethy、首席商務官 Eric Benevich，以及最後一次擔任首席醫療官的 Eiry Roberts。

During today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to review the risk factors discussed in our latest SEC filings. Following prepared remarks, we will strive to get to everyone's questions.

在今天的電話會議中，我們將做出前瞻性陳述。這些聲明受一定風險和不確定性的影響，我們的實際結果可能有重大差異。我鼓勵您查看我們最新的 SEC 文件中討論的風險因素。根據準備好的發言，我們將盡力回答每個人的問題。

Now I will turn the call over to Kyle.

現在我將把電話轉給凱爾。

Thanks, Todd. Good afternoon, everyone. Neurocrine has never been in a stronger position as we maintain an enterprise-wide focus on execution and evolution. Even with external factors continuing to create market volatility, we remain focused on controlling what we can, executing with discipline to meaningfully deliver for both patients and shareholders.

謝謝，托德。大家下午好。由於我們在整個企業範圍內專注於執行和發展，Neurocrine 的地位從未如此強大。即使外部因素繼續造成市場波動，我們仍然專注於控制我們所能控制的範圍，嚴格執行，為患者和股東提供有意義的服務。

The first quarter reflected strong execution across both of our brands with record new patient starts for INGREZZA and encouraging early adoption of CRENESSITY. With reaffirmed guidance for INGREZZA and solid momentum heading into Q2, combined with an early but promising launch trajectory for CRENESSITY, we are well positioned to drive both near- and long-term revenue growth as we evolve from a single blockbuster to a multiple blockbuster neuroscience company. Amazing to see the efforts from our commercial and medical teams this quarter. Well done.

第一季反映了我們兩個品牌的強勁執行力，INGREZZA 的新患者數量創下了紀錄， CRENESSITY 的早期採用也令人鼓舞。憑藉對 INGREZZA 的重申指導和第二季度的強勁勢頭，再加上 CRENESSITY 早期但前景光明的發布軌跡，我們在從一家單一重磅炸彈發展成為一家多重磅炸彈神經科學公司的過程中，完全有能力推動近期和長期的收入增長。很高興看到本季我們的商業和醫療團隊所做的努力。做得好。

On the R&D front, our portfolio continues to advance meaningfully. We are encouraged by the progression of osavampator and NBI-'568 into Phase III registrational studies. The strong magnitude of effect demonstrated in both programs' Phase II proof-of-concept studies gives us confidence in continued investment. We are on track for expanding our muscarinic portfolio into new Phase II studies later this year. This includes NBI-'568 into bipolar mania and NBI-'570, our dual M1/M4 agonist into schizophrenia.

在研發方面，我們的產品組合持續取得顯著進展。osavampator 和 NBI-'568 進入第三階段註冊研究的進展令我們感到鼓舞。這兩個計畫的第二階段概念驗證研究所表現出的強大效果使我們對持續投資充滿信心。我們計劃在今年稍後將毒蕈鹼藥物組合擴展至新的 II 期研究。其中包括用於治療躁鬱症的 NBI-'568 和用於治療精神分裂症的 NBI-'570（我們的雙重 M1/M4 激動劑）。

From a leadership perspective, we are thrilled to welcome Dr. Sanjay Keswani as our incoming Chief Medical Officer in June. Dr. Eiry Roberts, our current CMO, will transition into a strategic advisory role where her expertise will continue to shape key programs.

從領導層的角度來看，我們很高興歡迎 Sanjay Keswani 博士於 6 月擔任我們的新首席醫療官。我們現任行銷長 Eiry Roberts 博士將轉任策略顧問，她的專業知識將持續影響關鍵專案。

In closing and reflecting on the quarter, I'm extremely proud of our team and progress. Our growing diversified revenue base, expanding pipeline and strong balance sheet, position us well to continue building on our momentum as a leading global neuroscience company.

總結並回顧本季度，我為我們的團隊和進步感到非常自豪。我們不斷成長的多元化收入基礎、不斷擴大的產品線和強勁的資產負債表，使我們能夠繼續保持作為全球領先神經科學公司的發展勢頭。

With that, I'll turn the call over to Matt.

說完這些，我會把電話轉給馬特。

Thank you, Kyle, and good afternoon. We made tremendous progress throughout the first quarter both with the reacceleration of new patient growth for INGREZZA and with their successful CRENESSITY launch. We are executing from a position of strength with these two growing commercial products, a robust clinical pipeline in CNS disorders and a strong financial foundation that provides flexibility for continued investment to drive shareholder value.

謝謝你，凱爾，下午好。我們在第一季取得了巨大的進展，INGREZZA 的新患者成長再次加速，CRENESSITY 也成功推出。我們憑藉這兩款不斷成長的商業產品、強大的中樞神經系統疾病臨床管線以及強大的財務基礎，在執行中佔據優勢地位，這為持續投資以推動股東價值提供了靈活性。

Starting with INGREZZA. We posted $545 million in first quarter product sales. As anticipated, first quarter sales were impacted by one less order week, patient reauthorization processes and gross-to-net dynamics. Although noisy, I do want to make a few very specific comments about the quarter in INGREZZA.

從 INGREZZA 開始。我們第一季的產品銷售額為 5.45 億美元。正如預期的那樣，第一季的銷售額受到訂單週減少、患者重新授權流程和總額與淨額動態的影響。儘管有些吵鬧，我還是想對 INGREZZA 本季發表一些非常具體的評論。

First, we had record new patient additions in the first quarter, which is a testament to the quality of our product, the dedication of our team and the continued unmet medical need. Second, effective April 1, 2025, we expanded our formulary coverage in Medicare Part D, which significantly increases patient access, providing a foundation to expand our customer base in the years to come.

首先，第一季我們新增患者數量創下了紀錄，證明了我們產品的品質、我們團隊的奉獻精神以及持續未滿足的醫療需求。其次，自 2025 年 4 月 1 日起，我們擴大了 Medicare Part D 中的處方集覆蓋範圍，這大大增加了患者的就醫機會，為未來幾年擴大客戶群奠定了基礎。

Finally, as Kyle mentioned, we are reaffirming our 2025 sales guidance range of $2.5 billion to $2.6 billion, which factors in the expected acceleration of new patient additions, offset by gross-to-net impact from contracting activities.

最後，正如 Kyle 所提到的，我們重申 2025 年的銷售指引範圍為 25 億美元至 26 億美元，其中考慮到了新病患增加的預期加速，但被承包活動對總銷售額和淨銷售額的影響所抵消。

Turning to CRENESSITY, where we just completed our first full quarter of launch. We achieved net revenue of $15 million, which includes 413 enrollment forms with 70% of dispenses receiving reimbursement. Although we are still early in our launch efforts, we're encouraged by this initial success.

談到 CRENESSITY，我們剛剛完成了發布的第一個完整季度。我們實現了 1500 萬美元的淨收入，其中包括 413 份登記表，其中 70% 的配藥獲得了報銷。儘管我們的發布工作仍處於早期階段，但這一初步成功令我們感到鼓舞。

A few financial comments. Our capital allocation priorities remain intact with our number 1 priority being investments to drive revenue growth; number two priority is investments to advance our R&D pipeline; and three, investments to enable business development; and lastly, consider returning capital to our shareholders.

一些財務評論。我們的資本配置重點保持不變，我們的首要任務是投資以推動收入成長；其次是投資以推進我們的研發管道；第三是投資以促進業務發展；最後，考慮向股東返還資本。

During the first quarter, we continued to reflect these priorities to drive revenue growth with investments in our expanded INGREZZA sales force and CRENESSITY launch. In addition, we continue to make investments advancing our pipeline in R&D with the initiation of two major Phase III programs.

在第一季度，我們繼續體現這些優先事項，透過投資擴大 INGREZZA 銷售團隊和 CRENESSITY 推出來推動收入成長。此外，我們繼續投資推動我們的研發項目，並啟動了兩個主要的第三階段項目。

Just a reminder, R&D expense for the first quarter of 2025 includes $45 million of milestone expense primarily for the initiation of our osavampator Phase III program in MDD, and we'll recognize $15 million in milestone expense in the second quarter for the initiation of NBI-'568 Phase III program in schizophrenia.

提醒一下，2025 年第一季的研發費用包括 4500 萬美元的里程碑費用，主要用於啟動我們在 MDD 中的 osavampator III 期計劃，並且我們將在第二季度確認 1500 萬美元的里程碑費用，用於啟動精神分裂症中的 NBI-'568 III 期計劃。

In addition, we've been able to retire 3.6 million shares over the past two quarters and have retained a strong balance sheet with approximately $1.8 billion in cash to support our commercial and clinical development strategies for continued growth.

此外，我們在過去兩個季度中已經回購了 360 萬股股票，並保留了強勁的資產負債表，擁有約 18 億美元現金，以支持我們的商業和臨床發展策略，實現持續成長。

With that, I will now hand the call over to Eric Benevich, our Chief Commercial Officer. Eric?

現在，我將把電話交給我們的商務長 Eric Benevich。艾瑞克？

Thanks, Matt. We're celebrating two significant milestones for INGREZZA. First, a couple of weeks ago was the eighth anniversary of FDA approval. Remarkably, eight years into the launch, our commercial and medical teams achieved record new patient starts in the first quarter despite a challenging payer environment. I want to take a moment and thank our teams for their exceptional dedication and performance.

謝謝，馬特。我們正在慶祝 INGREZZA 的兩個重要里程碑。首先，幾週前是 FDA 批准八週年。值得注意的是，推出八年後，儘管面臨嚴峻的付款環境，我們的商業和醫療團隊仍在第一季創下了新患者數量的紀錄。我想花點時間感謝我們的團隊的傑出奉獻和表現。

This second week of May also marks Tardive Dyskinesia Awareness Week. Currently, we estimate that just over 40% of patients with TD have been given a diagnosis to explain their abnormal movements, and less than 10% are currently receiving standard-of-care treatment with a VMAT2 inhibitor, such as INGREZZA.

五月的第二週也是遲發性運動障礙宣導週。目前，我們估計超過 40% 的 TD 患者得到了能夠解釋其異常運動的診斷，而目前不到 10% 的患者正在接受 VMAT2 抑制劑（例如 INGREZZA）的標準治療。

So there remains a significant opportunity for growth of the VMAT2 class and INGREZZA as the VMAT2 class leader. As part of our support for TD Awareness Week, Neurocrine continues to collaborate with the Movement Disorders Policy Coalition, mental health advocacy organizations, health care providers and policymakers nationwide to increase awareness, reduce stigma and drive diagnosis so that TD sufferers can access available treatment options. Matt provided a nice summary of INGREZZA and CRENESSITY performance in his opening remarks, and I'd like to provide additional color.

因此，VMAT2 級別和 INGREZZA 作為 VMAT2 級別領導者仍有很大的發展機會。作為 TD 宣傳週支持的一部分，Neurocrine 繼續與運動障礙政策聯盟、心理健康倡導組織、全國各地的醫療保健提供者和政策制定者合作，以提高認識、減少恥辱感並推動診斷，以便 TD 患者能夠獲得可用的治療選擇。馬特在開場白中對 INGREZZA 和 CRENESSITY 的表現進行了很好的總結，我想提供更多的內容。

First, we're pleased to have expanded formulary coverage from less than half to approximately 2/3 of Medicare PD and HD beneficiaries. While this affects our gross to net, access will be improved for our ACP customers and the patients they care for. We view these as important investments to ensure patient access today and into the future.

首先，我們很高興將處方集覆蓋範圍從不到一半擴大到醫療保險 PD 和 HD 受益人的約 2/3。雖然這會影響我們的總收入與淨收入，但我們的 ACP 客戶及其所照顧的患者的就醫體驗將會改善。我們認為這些都是重要的投資，以確保患者現在和未來都能獲得治療。

Second, as noted in our last call, we believe the inflation Reduction Act, or IRA, has notably influenced payer behavior and reimbursement dynamics, particularly for specialty medicines like INGREZZA. In the second half of last year, we saw an impact on the prior authorization process for new patients.

其次，正如我們上次電話會議中指出的那樣，我們認為《通貨膨脹削減法案》（IRA）顯著影響了付款人的行為和報銷動態，特別是對於 INGREZZA 等特種藥物。去年下半年，我們發現新病患的事先授權流程受到了影響。

In Q1, we saw the impact on the reauthorization process for continuing patients, which was a bit more challenging versus prior years. Regardless, our field sales and field reimbursement teams were persistent in their efforts to help health care providers and patients manage through evolving payer requirements. Great job, teams. Third, we reaffirmed our 2025 INGREZZA guidance.

在第一季度，我們看到了對繼續治療患者的重新授權流程的影響，與前幾年相比，這更具挑戰性。無論如何，我們的現場銷售和現場報銷團隊堅持不懈地努力幫助醫療保健提供者和患者滿足不斷變化的付款人要求。幹得好，各位團隊。第三，我們重申了 2025 年 INGREZZA 指導。

Looking forward, our growth strategy encompasses our recently expanded sales force, investments in improved formulary access and enhanced marketing initiatives that will strengthen INGREZZA's market-leading position as the only VMAT2 inhibitor that is highly effective, uniquely selective with therapeutic dosing from day one and proven across the widest range of patients.

展望未來，我們的成長策略包括最近擴大的銷售隊伍、對改進處方集訪問的投資以及加強的營銷舉措，這些將加強 INGREZZA 的市場領先地位，因為 INGREZZA 是唯一一種高效、從第一天起就具有獨特治療劑量選擇性且在最廣泛的患者中得到驗證的 VMAT2 抑製劑。

With continued significant unmet need across the tardive dyskinesia and Huntington's chorea patient communities, we anticipate sales to accelerate in Q2 and through the second half of 2025. And this momentum should position us well heading into 2026 and beyond. For CRENESSITY, while we're still in the very early stages, I'm pleased to say that the launch is exceeding our expectations.

由於遲發性運動障礙和亨廷頓舞蹈症患者群體中仍然存在大量未滿足的需求，我們預計銷售額將在第二季和 2025 年下半年加速成長。這種勢頭將使我們在 2026 年及以後取得良好進展。對於 CRENESSITY 來說，雖然我們仍處於早期階段，但我很高興地說，這次發布超出了我們的預期。

As Matt noted, in Q1, we received 413 treatment forms, which serve as a new prescription, and we reported $15 million in net sales. We're observing strong uptake across both pediatric and adult CAH patient populations with slightly higher initial adoption rates in pediatric and adolescent segments.

正如馬特所指出的，在第一季度，我們收到了 413 份治療表格，這些表格作為新處方，我們報告的淨銷售額為 1500 萬美元。我們觀察到兒科和成人 CAH 患者群體的採用率都很高，其中兒科和青少年群體的初始採用率略高。

The prescriber response has been particularly encouraging with good initial trial across all endocrinologist segments, including centers of excellence, pediatric endocrinologists and community adult endocrinologists. While it's too early to comment on longer-term outcomes, we're pleased with the warm reception of CRENESSITY from the medical and patient communities.

處方人員的反應尤其令人鼓舞，所有內分泌科部門（包括卓越中心、兒科內分泌科和社區成人內分泌科）的初步試驗都取得了良好的效果。雖然現在評論長期結果還為時過早，但我們很高興看到 CRENESSITY 受到醫學界和患者界的熱烈歡迎。

On the payer front, we noted that 70% of the dispensers in the quarter were reimbursed. Coverage requirements have generally aligned with our approved labeling, including diagnosis of classic CAH, patient age of four years or older and concurrent glucocorticoids therapy.

在付款人方面，我們注意到本季 70% 的藥劑師獲得了報銷。覆蓋範圍要求通常與我們批准的標籤一致，包括經典 CAH 的診斷、四歲或以上的患者年齡和同時進行的糖皮質激素治療。

As we move forward through the balance of the year, we expect more health plans to conduct formulary reviews and publish their coverage criteria. However, some plans may choose not to formally review Chrinecity and continue to review prescription claims via their exceptions process.

隨著今年餘下時間的推進，我們預計會有更多的健康計劃進行處方集審查並公佈其覆蓋標準。然而，一些計劃可能選擇不正式審查 Chrinecity，而是繼續透過其例外流程審查處方索賠。

Overall, initial metrics are trending in the right direction across all key performance indicators. But I do want to remind everyone that one quarter is too soon to define a trend for either adoption or reimbursement. We're going to learn a lot over the coming quarters specific to persistency, compliance rates and overall rate of adoption.

整體而言，所有關鍵績效指標的初始指標都朝著正確的方向發展。但我確實想提醒大家，一個季度的時間還不足以確定採用或報銷的趨勢。在接下來的幾個季度中，我們將學到很多有關持久性、合規率和整體採用率的知識。

If CRENESSITY ultimately delivers significant benefit in the real world as it did in clinical trials, we fully believe it can become the new standard of care together with cortisol replacement for CAH patients. Once more, I'd like to congratulate our commercial and medical teams for getting CRENESSITY off to such a great start.

如果 CRENESSITY 最終在現實世界中像在臨床試驗中一樣帶來顯著的益處，我們完全相信它可以與 CAH 患者的皮質醇替代品一起成為新的護理標準。我再次祝賀我們的商業和醫療團隊為 CRENESSITY 取得如此良好的開端。

So with that, I'll turn the call over to my colleague, Dr. Eiry Roberts, our Chief Medical Officer.

因此，我將把電話轉給我的同事、我們的首席醫療官 Eiry Roberts 博士。

Thanks, Eric, and good afternoon to everyone. We continue to make substantial progress advancing Neurocrine's early- to mid-stage clinical pipeline, particularly across our muscarinic portfolio, next-generation VMAT2 inhibitors and epilepsy programs.

謝謝，埃里克，大家下午好。我們繼續在推動 Neurocrine 的早期至中期臨床管線方面取得實質進展，特別是在我們的毒蕈鹼產品組合、下一代 VMAT2 抑制劑和癲癇計畫方面。

Today, I'll focus specifically on our late-stage registrational assets and key 2025 data milestones. I'll start with osavampator, our AMPA-positive allosteric modulator. I'm pleased to announce the initiation of all three randomized, double-blind, placebo-controlled studies evaluating its efficacy and safety as an adjunctive treatment for major depressive disorder. These studies will measure the change in total MADRS from baseline to day 56 as their primary endpoint with top line data expected throughout 2027.

今天，我將特別關注我們的後期註冊資產和 2025 年關鍵資料里程碑。我將從 osavampator（我們的 AMPA 陽性變構調節劑）開始。我很高興地宣布，三項隨機、雙盲、安慰劑對照研究已啟動，評估其作為重度憂鬱症輔助治療的療效和安全性。這些研究將測量從基線到第 56 天的總體 MADRS 變化作為其主要終點，預計全年都會獲得頂線數據。

Turning to our selective M4 agonist, NBI-'568. Just last week, we announced the initiation of the first of three Phase III registrational studies to evaluate the efficacy, safety and tolerability of NBI-'568 as a potential treatment for schizophrenia.

轉向我們的選擇性 M4 激動劑 NBI-'568。就在上週，我們宣布啟動三項 III 期註冊研究中的第一項，以評估 NBI-'568 作為精神分裂症潛在治療方法的有效性、安全性和耐受性。

We anticipate initiating the two additional studies in the coming months. All three double-blind, placebo-controlled trials comparing the 20-milligram dose of NBI-'568 versus placebo with reduction from baseline in the positive and negative in scale, or PANSS, at week five as the primary endpoint.

我們預計在未來幾個月內啟動另外兩項研究。所有三項雙盲、安慰劑對照試驗均比較了 20 毫克劑量的 NBI-'568 與安慰劑，以第五週時陽性和陰性量表 (PANSS) 相對於基線的減少作為主要終點。

We expect top line data from these studies in the 2027-2028 time frame. This year, we will report top line data from two Phase III studies of valbenazine, the first in adjunctive treatment of schizophrenia, which serves as a proof-of-concept study for VMAT2 inhibition in this disease state. While these results will guide the development of our next-generation VMAT2 inhibitors, including NBI-'890 and '675, we do not plan to expand the valbenazine label for this indication.

我們預計這些研究將在 2027-2028 年期間獲得最重要的數據。今年，我們將報告兩項 Valbenazine III 期研究的頂線數據，第一項是用於治療精神分裂症的輔助治療，作為該疾病狀態下 VMAT2 抑制的概念驗證研究。雖然這些結果將指導我們開發下一代 VMAT2 抑制劑，包括 NBI-'890 和 '675，但我們並不打算擴大伐貝那嗪的適應症範圍。

The second readout expected later this year will evaluate valbenazine's efficacy in treating dyskinetic cerebral palsy. With no currently approved treatments for the 75,000 to 100,000 patients in the US living with DCP, successful results could lead to a label expansion for this indication.

預計今年稍晚將發布第二次讀數，以評估伐貝那嗪治療運動障礙性腦性麻痺的療效。目前，美國有 75,000 至 100,000 名 DCP 患者，但尚無核准的治療方法，成功的治療結果可能會導致此適應症的標籤擴展。

For NBI-'770, our NMDA NR2B subreceptor-negative allosteric modulator, the Phase II dose-finding study in major depressive disorder remains on track for top line data in the second half of 2025. This study's primary outcome measure focuses on the MADRS change from baseline to day 5, potentially demonstrating more rapid onset compared to osavampitor's Phase III day 56 endpoint.

對於我們的 NMDA NR2B 亞受體負變構調節劑 NBI-'770，重度憂鬱症的 II 期劑量探索研究仍有望在 2025 年下半年獲得頂線數據。這項研究的主要結果測量重點是從基線到第 5 天的 MADRS 變化，與 osavampitor 的 III 期第 56 天終點相比，可能表明起效更快。

As this marks my final earnings call as Neurocrine's Chief Medical Officer, I'd like to share some closing observations. Neurocrine stands stronger than ever, making this an optimal time for the transition. Our industry-leading pipeline continues to grow fueled by Jude Onyia's excellent progress establishing a sustainable internal innovation engine.

這是我作為 Neurocrine 首席醫療官的最後一次財報電話會議，我想分享一些總結性的評論。Neurocrine 比以往任何時候都更強大，這使得現在成為轉變的最佳時機。在 Jude Onyia 建立可持續內部創新引擎的出色進展的推動下，我們行業領先的產品線繼續增長。

My seven plus years at Neurocrine have been marked by remarkable evolution, and I'm confident in Sanjay Caswani's capability to lead as the next Chief Medical Officer. I look forward to maintaining an active advisory role supporting both Sanjay and our late-stage program teams.

我在 Neurocrine 任職七年多，取得了顯著的進步，我相信 Sanjay Caswani 有能力擔任下一任首席醫療官。我期待繼續發揮積極的顧問作用，為桑杰和我們的後期專案團隊提供支援。

Finally, I extend my gratitude to the Board, Kevin, Kyle, my Neurocrine colleagues and all our external partners, including the investment community. Neurocrine is well positioned to help countless future patients, and I'm proud to have contributed to this journey.

最後，我要向董事會、凱文、凱爾、我的 Neurocrine 同事以及所有外部合作夥伴（包括投資界）表示感謝。Neurocrine 有能力幫助無數未來的患者，我很自豪能夠為這一歷程做出貢獻。

With that, I'll hand the call back to Kyle. Kyle?

說完這些，我就把電話轉回給凱爾。凱爾？

Thanks, Eiry. And just to pause here a moment before we move into questions. I do want to take a moment to recognize Eiry for her many contributions over the years. Eiry has played a vital role in shaping Neurocrine into what it is today and really helped many thousands of patients along the way.

謝謝，Eiry。在我們進入提問環節之前，請稍停片刻。我確實想花點時間來表彰 Eiry 多年來所做的諸多貢獻。Eiry 在 Neurocrine 的形成過程中發揮了至關重要的作用，並在過程中真正幫助了成千上萬的患者。

If I think about the future here with Eiry, she will continually be a player and help us along the way. But as we mentioned just a moment ago, this will be her final earnings call as an executive of the company. So Eiry, once again, thank you for your dedication, your leadership and your support over the years.

如果我考慮與 Eiry 的未來，她將繼續成為一名球員並一路幫助我們。但正如我們剛才提到的，這將是她作為公司高層的最後一次財報電話會議。所以，Eiry，再次感謝您多年來的奉獻、領導和支持。

With that, let's open it up to questions.

好了，讓我們開始提問吧。

(Operator Instructions)

（操作員指示）

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

Hey, thanks for taking my questions, and Eiry, congrats. Always good to work with you. Two quick ones. As it relates to INGREZZA, it sounds like the quarter was not as challenging as some feared. I was wondering if you could comment on what you're seeing into 2Q and if you feel like getting back to the prior growth rate at some point is attainable. And then just on CRENESSITY, congrats on the progress. Should we be looking at this 400 number as a bolus and then it can attenuate from here? Or do you feel like it's just the beginning? Thank you.

嘿，謝謝你回答我的問題，Eiry，恭喜你。很高興與您合作。兩個簡單的。就 INGREZZA 而言，聽起來本季並不像有些人擔心的那樣具有挑戰性。我想知道您是否可以評論一下您對第二季度的看法，以及您是否認為在某個時候恢復到之前的成長率是可以實現的。然後就 CRENESSITY 而言，祝賀所取得的進展。我們是否應該將這個 400 數字視為一個推注量，然後它可以從這裡衰減？或者您覺得這只是一個開始？謝謝。

Paul, this is Kyle. Maybe I'll start here and then I'll ask Eric and Matt to chime in. On INGREZZA, I think when we look at Q1, you probably heard us talking about the challenges of the quarter over the past couple of months.

保羅，這是凱爾。也許我會從這裡開始，然後我會請 Eric 和 Matt 參與其中。關於 INGREZZA，我想當我們回顧第一季時，您可能聽過我們談論過去幾個月本季面臨的挑戰。

I think it played out exactly as we expected it. We had that low momentum coming into the year, the difficulties of reauthorization, the one less selling week the, hits on gross to net, all those were factors that came into play. But just to round out the quarter, we saw that one element that gives us great confidence going into the remainder of the year, and that is the momentum that you get from having that growth in new patient starts.

我認為事情正如我們預期的那樣發展。進入今年以來，我們的發展勢頭一直很低迷，重新授權的困難，銷售週數減少一周，總銷售額與淨銷售額的比率受到打擊，所有這些都是造成這一現象的因素。但為了讓本季更加圓滿，我們發現一個因素讓我們對今年剩餘時間充滿信心，那就是新患者數量的成長帶來的動力。

And I think it goes without saying that the growth in new patient starts was the record that we've seen of all time in terms of a quarter, and it came in the most challenging quarter. So I think there's a lot to be said there for momentum going into Q2, the remainder of the year and really just an amazing job by the team out there in the field.

我認為毋庸置疑，新患者數量的成長是我們有史以來看到的季度成長記錄，而且它出現在最具挑戰性的一個季度。因此，我認為第二季和今年剩餘時間的勢頭非常強勁，而且該領域的團隊確實做得非常出色。

So I think that we have that momentum going into the remainder of the year. We have a number of elements that we put in place late last year that will play a factor for us positively this year. We mentioned the sales force expansion, the expanded access that we have now and other marketing initiatives that we'll be kicking off here very shortly. All these things will help us to continue the recovery of growth in Q2 and an acceleration the second half of the year.

所以我認為我們在今年剩餘時間內將保持這種勢頭。我們在去年年底實施的多項措施將對我們今年的發展產生積極影響。我們提到了銷售團隊的擴張、我們現在擁有的擴大的管道以及我們很快就會啟動的其他行銷計劃。所有這些都將有助於我們在第二季度繼續恢復成長並在下半年加速成長。

In terms of CRENESSITY, maybe I'll let Eric speak to that and we can go from there.

就 CRENESSITY 而言，也許我會讓 Eric 談談這個問題，然後我們可以從那裡開始。

Yes. No, Paul, I think your question is in terms of should we expect this number of treatment forms or new patient NRx referrals going forward. As I mentioned in my prepared remarks, we only have one quarter of experience with this launch. Obviously, we're really pleased with the adoption that we're seeing. But ultimately, we need a little bit more time to understand what that pattern is going to look like.

是的。不，保羅，我認為你的問題是關於我們是否應該預期未來會有這麼多的治療表格或新的患者 NRx 轉診。正如我在準備好的發言中提到的那樣，我們對這次發布只有四分之一的經驗。顯然，我們對所看到的採用感到非常高興。但最終，我們需要更多時間來了解這種模式會是什麼樣子。

And so as we go forward, we'll continue to share what the treatment form or referral rate is and obviously provide additional metrics like we did in this particular quarter. But I think it's too soon to tell. But I will reiterate, it's -- we're off to a great start. And certainly, this exceeded our expectations at this phase.

因此，隨著我們不斷前進，我們將繼續分享治療形式或轉診率，並顯然提供額外的指標，就像我們在本季所做的那樣。但我認為現在下結論還為時過早。但我要重申，我們已經有了一個好的開始。當然，這超出了我們現階段的預期。

Thanks, guys.

謝謝大家。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞。

Hi. This is TV on for Akash. Thank you for taking our question. Similarly to what was just asked, could you provide any color on CRENESSITY's sort of payer dynamics moving forward? 70% is higher than we had anticipated. So just wondering how you expect it to move forward from here. Thank you.

你好。這是為 Akash 開的電視。感謝您回答我們的問題。與剛才的問題類似，您能否提供有關 CRENESSITY 未來付款人動態的任何資訊？70%高於我們的預期。所以我只是想知道您期望它從現在開始如何發展。謝謝。

Yes. Just like with the adoption, the reimbursement, I think, exceeded our expectations as well. As I mentioned earlier, 70% of the fills in the quarter were reimbursed. And certainly, that's favorable for one quarter in, but I would like to caution everyone and remind them that this is still a product that, for the most part, hasn't gone through formulary reviews. And so for the most part, we're talking about reimbursement via the exceptions process.

是的。就像收養一樣，我認為報銷金額也超出了我們的預期。正如我之前提到的，本季 70% 的填充量都得到了報銷。當然，這對於一個季度來說是有利的，但我想提醒大家，這仍然是一種在很大程度上尚未經過處方審查的產品。因此，在大多數情況下，我們討論的是透過例外流程進行報銷。

And so as we move through the year, we do expect that some of the plans, maybe most of the plans, will be doing formal reviews of CRENESSITY and determining what their coverage criteria look like. But at this stage, it's still formulary exceptions, and we're off to a great start in terms of securing reimbursement.

因此，隨著時間的推移，我們確實預計一些計劃，也許是大多數計劃，將對 CRENESSITY 進行正式審查，並確定其覆蓋標準。但現階段，這仍然是處方例外，我們在確保報銷方面已經有了良好的開端。

Yes. This is Matt. Just a big shout-out to the market access team. Kudos to them for educating all the payers in terms of the disease burden and also the benefits that CRENESSITY could potentially provide. This is a high-value medicine helping a lot of patients, and it's been fairly seamless between prescription written and ultimately getting filled. And so do want to give that kudos to the team that has been working hard on that.

是的。這是馬特。向市場准入團隊大聲呼喊。他們向所有付款人普及了疾病負擔以及 CRENESSITY 可能提供的益處，值得稱讚。這是一種高價值藥物，可以幫助許多患者，並且從開處方到最終取藥的整個過程相當順暢。因此，我非常想向一直為此努力工作的團隊表示敬意。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi, good afternoon. Thanks for taking my question. First, Eiry, great job on everything and good luck on your next chapter. I did want to ask about the share split between what you're seeing now on INGREZZA versus Teva for new-to-treatment TD patients. I don't know if you could share any color on that. And then on CRENESSITY, can you give us a split of what percent of patients, and I'm sorry if I missed it, are kids versus adults in the early innings of usage? Thanks.

嗨，下午好。感謝您回答我的問題。首先，Eiry，你做得很好，祝你下一章一切順利。我確實想問一下對於新接受治療的 TD 患者來說，您現在看到的 INGREZZA 和 Teva 的份額分配。我不知道您是否可以分享一些關於此方面的內容。然後關於 CRENESSITY，您能否告訴我們在使用初期，患者中兒童和成人的百分比是多少？如果我錯過了，請見諒。謝謝。

Yes. So we haven't provided historically share split exactly because if you look at the syndicated prescription data, it underreports INGREZZA. And so we've always cautioned to not look at the numbers as exact measures. But overall, what we have said is that we have had the majority of prescriptions in TD, and we continue to have the majority of prescriptions. That's for both TRx and for NRx. And so we'll leave it at that.

是的。因此，我們沒有提供歷史上的股份分割情況，因為如果你查看聯合處方數據，它會低估 INGREZZA。因此，我們一直告誡不要將數字視為精確的衡量標準。但總體而言，我們所說的是，我們在 TD 擁有大多數處方，並且我們將繼續擁有大多數處方。這適用於 TRx 和 NRx。我們就到此為止吧。

The other thing that you were asking about in terms of the split or the demographics of the patient population, very early on. What we were seeing was sort of an equal distribution of pediatric and adult patients and pretty equal distribution of females versus males. But as we've gotten more treatment forms in and the launch continues to mature, we have seen that it's starting to trend in the direction that we expected prior to the approval, which is more pediatric and adolescent patients than adult and more female versus male.

您很早就詢問了有關患者群體分佈或人口統計的另一件事。我們看到的是兒科和成人患者的分佈大致相等，女性和男性患者的分佈也相當均勻。但隨著我們獲得更多的治療形式並且產品推出不斷成熟，我們已經看到它開始朝著我們在批准之前預期的方向發展，即兒科和青少年患者多於成人患者，女性患者多於男性患者。

Once again, we've got a long way to go in terms of understanding the launch dynamics, and one quarter does not make a trend. But ultimately, it is essentially trending in the direction that we expected it to prior to the launch.

再次強調，我們在理解發布動態方面還有很長的路要走，一個季度並不能形成一種趨勢。但最終，它基本上朝著我們在發布之前預期的方向發展。

Phil Nadeau, TD Cowen.

菲爾·納多 (Phil Nadeau)，TD Cowen。

Good afternoon. Thanks for taking our question. Let us add our congratulations to Eiry on a great career at Neurocrine. Two from us as well. First, on INGREZZA trends. INGREZZA grew 15% from Q1 to Q2 in 2024. Can you give us some sense of what's likely to happen in Q2 of '25? It seems like with one additional Tuesday, at least 8% growth is reasonable. But how are some of the factors that impacted Q1 transitioning into Q2? And what should that do to sales?

午安.感謝您回答我們的問題。讓我們共同祝賀 Eiry 在 Neurocrine 取得的輝煌成就。我們也有兩個。首先，關於INGREZZA的趨勢。INGREZZA 2024 年第一季至第二季成長了 15%。您能否向我們介紹一下 2025 年第二季可能發生的情況？看起來，如果再增加一個星期二，至少 8% 的成長是合理的。但是影響第一季過渡到第二季的一些因素是怎麼樣的呢？這對銷售有何影響？

And then second, just a follow-up -- a brief follow-up question on CRENESSITY. You mentioned that CRENESSITY was relatively seamless from script to fill. Can you give us some sense of the time, which time it takes from prescription being written or an enrollment start being received to when the patient actually gets drug in hand? Thanks.

其次，只是一個後續問題——關於 CRENESSITY 的一個簡短的後續問題。您提到 CRENESSITY 從腳本到填充都相對無縫。您能否告訴我們一下從開處方或開始收到登記到病人實際拿到藥物需要多長時間？謝謝。

Thanks, Phil, for the questions, as always. Yes, from a Q1, Q2 dynamic, you would expect a nice step up. You do gain back on order week on the quarter. That does provide a sequential benefit. You also have the record numbers in new patients that we mentioned earlier and then the natural recovery of refill rate per patient.

一如既往，感謝菲爾提出的問題。是的，從 Q1、Q2 的動態來看，您會期待有良好的進步。您確實在本季度的訂單週獲得了收益。這確實帶來了連續的好處。您還擁有我們之前提到的新患者數量的創紀錄數量，以及每位患者的補充率的自然恢復。

The one aspect that you will want to contemplate that's different than previous years, as mentioned, we did enter into some contracting during the quarter. And from -- and as a result of that, we do -- we will have a sequential hit in gross to net. I'd call it slightly down from Q1 to Q2. That will push down the growth profile just a little bit. But overall, you would expect a nice step up for Q2 and it positions us well for the second half of the year.

您需要考慮的一個方面與前幾年不同，正如所提到的，我們在本季度確實簽訂了一些合約。而 — — 也正是由於這一點，我們 — — 總額與淨額將會受到連續打擊。我認為從第一季到第二季會略有下降。這將會稍微降低經濟成長率。但總體而言，您預計第二季將有良好的成長，這為我們下半年的業績奠定了良好的基礎。

As it relates to time, I would just say that it's time to ultimately get a fill or get the reimbursement for CRENESSITY. It's still too early in the cycle to give any specific number. As you have heard us say before, patients, once they have an enrollment form written, it's typically a five day to seven day process where the pharmacy is trying to get reimbursement.

就時間而言，我只想說現在是時候最終填補或獲得 CRENESSITY 的報銷了。現在給出任何具體數字還為時過早。正如您之前聽到我們說的，患者一旦填寫了登記表，通常需要五到七天的時間才能從藥房獲得報銷。

And whether the patient has had reimbursement granted or not, a patient will ultimately get a fill. And as we alluded to in the percentages we provided, 30% did get free goods during the quarter. But overall, team performed very well, and I think the feedback on our pharmacy channel has gone great so far.

無論患者是否獲得報銷，患者最終都會得到治療。正如我們在提供的百分比中提到的那樣，30% 的人在本季度確實獲得了免費商品。但總體而言，團隊表現非常出色，我認為到目前為止，我們藥局管道的回饋非常好。

That's very helpful. Thank you.

這非常有幫助。謝謝。

Brian Abrahams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

Hey, guys. Thanks very much for taking my questions. Congrats to Eiry on a great career and -- at Neurocrine, and congrats on the strong CRENESSITY start. Maybe just two quick ones for me on CRENESSITY. Can you provide any more specifics on the proportions of patients being treated at centers of excellence versus community centers and how these doctors are managing the glucocorticoid down titration, whether that differs at all?

嘿，大家好。非常感謝您回答我的問題。恭喜 Eiry 在 Neurocrine 取得了偉大的職業生涯，並祝賀 CRENESSITY 取得了良好的開端。對我來說，關於 CRENESSITY 可能只有兩個簡短的問題。您能否提供更多關於在卓越中心和社區中心接受治療的患者比例的細節，以及這些醫生如何管理糖皮質激素的滴定，是否有任何不同？

And then on INGREZZA, as you continue to invest in formulary access, can you give us any more specifics on how to think about contracting cadence going forward and what the pricing trends might look like beyond second quarter of this year? Thanks.

然後關於 INGREZZA，隨著您繼續投資於處方集訪問，您能否向我們提供更多細節，說明如何考慮未來的簽約節奏，以及今年第二季度以後的定價趨勢如何？謝謝。

Yes. So let me take a crack at the second question first and then tackle the CRENESSITY question. Eiry might want to chime in as well. Contracting cadence, so we've always said that our priority is to maximize access for patients. And historically, we have contracted, but we've been fairly prudent in terms of selecting where we want to contract and where we think it can make a difference in terms of improving access.

是的。因此，讓我先試著回答第二個問題，然後再解決 CRENESSITY 問題。Eiry 可能也想加入進來。收縮節奏，所以我們一直說我們的首要任務是最大限度地為患者提供就醫機會。從歷史上看，我們確實簽訂了合同，但在選擇簽訂合同的地點以及我們認為可以在改善准入方面有所作為的地點方面，我們一直相當謹慎。

In the prepared remarks, we talked about increasing coverage in the Medicare segment for the TD market and the HC market from less than half to approximately 2/3 with the most recent rebate agreement. And we're going to continue to monitor the environment.

在準備好的評論中，我們談到了透過最新的回扣協議將 TD 市場和 HC 市場的醫療保險覆蓋率從不到一半提高到大約 2/3。我們將繼續監測環境。

I don't think there's anything immediate that could happen, certainly, nothing that we're anticipating in terms of additional rebate agreements. But certainly, if anything does happen, if we enter into any additional rebate agreements, we would flag that going forward. But ultimately, the benefit of improving access certainly accrues starting this year but carries into 2026 as well. So I think it sets us up well for the future.

我認為不會立即發生任何事，當然，我們也不會期待任何額外的回扣協議。但可以肯定的是，如果確實發生任何事情，如果我們達成任何額外的回扣協議，我們都會在未來標記。但最終，改善通道的好處肯定會從今年開始顯現，而且會延續到 2026 年。所以我認為這為我們的未來做好了準備。

With regards to your question about, I'll call it, sources of business, volume of treatment form coming in from centers of excellence versus the community. Right now, what we're seeing is that it's really across the Board. We have seen adoption and referrals coming in from those centers of excellence. But keep in mind, there's not very many of them . There's only nine accredited centers of excellence, accredited by the Cares Foundation, a similar number that have most of those services, but they're not accredited.

關於您的問題，我將其稱為業務來源，即來自卓越中心與社區的治療量。現在，我們看到的是，這種現象確實普遍存在。我們已經看到這些卓越中心的採用和推薦。但請記住，他們的數量並不多。獲得 Cares Foundation 認可的卓越中心只有 9 個，雖然有類似數量的卓越中心提供大部分服務，但並未獲得認可。

So we are seeing adoption in referrals also from community pediatric endocrinologists as well as pediatric adult endocrinologists. And it kind of ties back to the comments that we made earlier about really seeing that CRENESSITY is being embraced by the broader endocrinology community. Anything to add, Eiry?

因此，我們看到社區兒科內分泌學家和兒科成人內分泌學家也採用了轉診方法。這與我們先前的評論有關聯，我們確實看到 CRENESSITY 受到了更廣泛的內分泌學界的歡迎。還有什麼要補充的嗎，Eiry？

No, just about the steroid reduction piece of the question as well. So the first thing, just to build on what Eric was saying, we've been incredibly impressed by the engagement of the endocrine community around CRENESSITY and the level of interest in gaining additional education on how to use the medicine effectively and safely.

不，只是關於類固醇減少部分的問題。因此，首先，基於 Eric 所說的內容，我們對內分泌界圍繞 CRENESSITY 的參與以及對如何有效和安全地使用該藥物的額外教育的興趣程度印象深刻。

I think in general, as our medical team has engaged, there's a few things that we're learning. First of all, I think there is a real enthusiasm about the safety and tolerability profile that we saw with CRENESSITY in the registration studies. And so that creates a foundation for a good opportunity to start the medicine in a patient.

我認為總的來說，隨著我們的醫療團隊的參與，我們學到了一些東西。首先，我認為人們對我們在註冊研究中看到的 CRENESSITY 的安全性和耐受性概況表現出了真正的熱情。這為在患者身上開始用藥創造了良好的機會基礎。

The second thing is the label that we achieved for the medicine, which is broad in its description and doesn't require a very specific or guided information on steroid reduction. And what that allows us to do is engage with clinicians as they ask questions of the medical team to provide guidance where appropriate while still ensuring that on an individualized basis, the clinician and the patient can decide what's the right regimen for the patient and how to reduce the steroids effectively.

第二件事是我們為該藥物製作的標籤，其描述很廣泛，不需要關於減少類固醇的非常具體或指導性的信息。這樣，我們就可以與臨床醫生交流，向醫療團隊提問，在適當的情況下提供指導，同時確保臨床醫生和患者能夠根據個人情況決定適合患者的治療方案以及如何有效減少類固醇。

All in all, many of these patients are just getting started on CRENESSITY and just getting started on that journey. So I think we'll learn more in the coming quarters.

總而言之，許多患者才剛開始使用 CRENESSITY，並且剛開始這段旅程。所以我認為我們將在接下來的幾個季度中了解更多。

Thanks very much.

非常感謝。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

Thanks. Just staying with CRENESSITY, can you talk about the mix between starts in adults versus pediatric and adolescent patients? Bearing in mind that these are early days, but can you talk to which of these patient groups, if any, you're gaining more early traction in? Thank you.

謝謝。延續 CRENESSITY，您能談談成人患者與兒童和青少年患者的混合嗎？請記住，現在還處於早期階段，但是您可以與哪些患者群體（如果有的話）談談您在早期階段獲得了更多的關注嗎？謝謝。

Yes, David. I think I mentioned earlier that at the very beginning of the launch, in other words, the beginning of Q1, we were seeing -- it was about even split between adults and the pediatric patient population. But as we went through the quarter, we saw that we were getting more treatment form referrals for those pediatric and adolescent pages -- patients. So we're starting to see a trend towards greater uptake in the younger population, which is what we expected to see.

是的，大衛。我想我之前提到過，在發布之初，換句話說，第一季初，我們看到——成人和兒科患者群體的比例大致相等。但隨著本季的推進，我們發現我們獲得了更多兒科和青少年患者的治療轉診。因此，我們開始看到年輕族群接受度較高的趨勢，而這正是我們所期望看到的。

Now we'll have to see how things shake out over the next several quarters. As I said before, when you've got very little data to work with, things can swing in one direction or another. But as we get more utilization, more adoptions in the community, I think we'll have a better sense of how the launch is going.

現在我們必須看看未來幾季的情況如何。正如我之前所說，當你只有很少的數據可用時，事情可能會朝著一個方向或另一個方向發展。但隨著我們得到更多的利用，在社群中得到更多的採用，我認為我們會更了解發布的進度。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

Hey, guys. Thanks so much for taking my question, and best of luck, Eiry, in everything you pursue going forward. The -- on the INGREZZA and the record number of patient starts, what should we attribute this to in terms of thinking about your share of voice gain relative to AUSTEDO XR?

嘿，大家好。非常感謝您回答我的問題，並祝 Eiry 在未來的一切追求中一切順利。關於 INGREZZA 和創紀錄的患者開始數量，從相對於 AUSTEDO XR 的聲音份額增益來看，我們應該將其歸因於什麼？

I know you pointed to that as a headwind coming into the year. How do we think about -- have you stabilized your share of voice? Are you -- or were there other factors like TD market expansion or other factors we should be considering? Thanks so much.

我知道您指出這是今年的一大阻力。我們如何思考－您是否已經穩定了自己的發言權？您——或者還有其他因素，例如 TD 市場擴張或其他我們應該考慮的因素嗎？非常感謝。

Yes. I mean, obviously, we made an investment last year to expand our sales force, and we targeted that investment towards the areas that we thought would yield the best results and specifically into psychiatry and into long-term care.

是的。我的意思是，顯然，我們去年進行了一項投資來擴大我們的銷售隊伍，我們將這項投資瞄準了我們認為會產生最佳效果的領域，特別是精神病學和長期護理。

So we're starting to see the tangible benefit of that. We had cautioned that when you expand the sales team in the near term, it can be disruptive. It can negatively impact your productivity. But as the newer representatives become more productive and they start to level to the level of their colleagues that have been in the field for some period of time, then you start to see the tangible benefits. And I think that's really what we're seeing as it manifests in terms of new patient starts.

因此我們開始看到它所帶來的實質好處。我們曾警告說，短期內擴大銷售團隊可能會造成混亂。它會對您的工作效率產生負面影響。但隨著新代表的工作效率提高，並開始達到已經在該領域工作了一段時間的同事的水平，您就會開始看到切實的好處。我認為這正是我們所看到的，從新病人的開始就可以看出來。

So we're certainly pleased to see a record number of new patient starts in Q1. But we've also mentioned that we've implemented some newer marketing initiatives. And really, the idea is to be better at helping our customers to appreciate the meaningful differences between INGREZZA and the tetrabenazine products that are out there.

因此，我們很高興看到第一季新患者數量創下紀錄。但我們也提到，我們已經實施了一些更新的行銷措施。實際上，我們的想法是更好地幫助我們的客戶認識到 INGREZZA 與現有的丁苯那嗪產品之間的有意義的差異。

So between having more people in the field calling on the right accounts and doing a better job of differentiating INGREZZA, I think really, those are the two elements that probably have the biggest impact in terms of driving those new patient starts. Thanks so much for taking my question.

因此，我認為，在讓更多人接觸正確的客戶和更好地區分 INGREZZA 之間，這兩個因素可能對推動新患者開始治療產生最大的影響。非常感謝您回答我的問題。

Josh Schimmer, Cantor.

喬許希默（Josh Schimmer），領唱。

Thanks so much for taking the questions. A couple of quick ones. Has your contracting for INGREZZA contemplated the AUSTEDO IRA price negotiation implementation? Or will you have to renegotiate as you get closer to that kicking in, in 2027?

非常感謝您回答這些問題。幾個簡單的。您與 INGREZZA 簽訂的合約是否考慮過 AUSTEDO IRA 價格談判的實施？或者，隨著 2027 年即將生效，您是否必須重新進行談判？

And then just in terms of this -- the record number of starts, just trying to align that -- your comments, I guess, around last year and early into this year that you didn't really expect your redeployed sales force to start to contribute meaningfully until later this year. Have they -- has that contribution occurred earlier than you expected? Or are you still waiting for a significant inflection from their contributions? Thank you.

然後就這一點而言 - 創紀錄的開工數量，只是想將其與此相一致 - 我猜，您在去年和今年年初的評論中說，您並沒有真正期望重新部署的銷售人員直到今年晚些時候才會開始做出有意義的貢獻。他們—這項貢獻是否比您預期的更早發生？還是您仍在等待他們的貢獻帶來重大轉變？謝謝。

Maybe I'll -- Josh, this Kyle. I'll take on the quick question on the contracting piece. I think if you look at our history on contracting in the past, it has been really the Northstar here is to maximize patient access, and that's always been how we viewed contracting. We've done that in years in the past. We've also walked away from contracting at certain time points when that was not the case.

也許我會——喬希，這個凱爾。我將快速回答有關承包部分的問題。我認為，如果你回顧我們過去的承包歷史，你會發現我們真正的目標是最大限度地提高病人的就醫機會，而這一直是我們對承包的看法。我們過去幾年已經這樣做了。當情況並非如此時，我們也會在某些時間點放棄簽訂合約。

I think when we look at the strategy overarching is to have a parity type of situation with other products in this space to make sure patients have as many options as possible. The thing that's different moving forward is IRA does bring a complication into the story about how we view contracting and maximizing patient access. So this is a variable. Now that's part of the equation that's growing in magnitude of its significance. And that is something that we have an eye on, in particular, for our competitors' iPay moment in 2027.

我認為，當我們考慮策略時，首要的是與該領域的其他產品保持同等水平，以確保患者擁有盡可能多的選擇。向前發展的不同之處在於，IRA 確實為我們如何看待簽約和最大化患者就醫帶來了複雜性。所以這是一個變數。現在，這是方程式的一部分，其重要性正在增加。這是我們特別關注的事情，尤其是 2027 年我們的競爭對手的 iPay 時刻。

Obviously, contracting that we do now is really with an eye on 2026. And in some cases, you can pull forward into the same year. But we do look at that as something that's important for us to continue looking at. And as things change and evolve over the coming months and year, we will certainly keep the external community up to date in case any changes in our contracting approaches of change. But right now, we're happy where we landed with the expanded access here starting this quarter and moving into the remainder of the year.

顯然，我們現在簽訂的合約確實著眼於 2026 年。在某些情況下，您可以提前到同一年。但我們確實認為這是一件值得我們繼續關注的重要事情。隨著未來幾個月和一年中情況的變化和發展，如果我們的承包方式發生任何變化，我們一定會向外部社區通報最新情況。但目前，我們很高興看到從本季開始並持續到今年剩餘時間這裡的訪問範圍不斷擴大。

Eric, you have anything to add to that?

艾瑞克，你對此還有什麼要補充的嗎？

Yes. Just in general, especially in the Medicare space, you go year-to-year with your contracts. Several of the agreements that we have in place, however, carry us through 2025 and the entirety of 2026. And so that does provide some stability from a planning perspective and right up to the doorstep of that IP moment, as Kyle described.

是的。一般來說，特別是在醫療保險領域，合約是逐年簽訂的。然而，我們已達成的幾項協議將幫助我們度過 2025 年和整個 2026 年。正如 Kyle 所描述的，這確實從規劃角度提供了一定的穩定性，直到 IP 時刻的到來。

The second piece was really around the contribution of the expanded sales force. Was it earlier than what we expected? I would say, no. It was pretty much in line with our expectations. Recall that the expanded sales team hit the field in Q4. And we had said that we need a few quarters for the team to kind of hit their stride. And we saw that really manifest with the record new patient starts, especially as we moved through Q1.

第二部分其實是關於擴大銷售團隊的貢獻。是不是比我們預期的早？我想說，不。這基本上符合我們的預期。回想一下，擴大的銷售團隊在第四季開始投入工作。我們說過，我們需要幾個季度的時間才能讓球隊達到最佳狀態。我們看到，隨著新患者數量的增加，這一點得到了明顯體現，尤其是在第一季。

Keep in mind that Q1 is a quarter every year that we have to go through, somewhat of a right of passage because of the many, many patients that need reauthorization. So kind of working our way through that with our customers, with the HCPs and the pharmacies does consume a lot of our effort in Q1 every year. But we're able to do that in tandem with driving new patient starts.

請記住，第一季是我們每年必須經歷的一個季度，這在某種程度上是一種通過權，因為有許多患者需要重新授權。因此，每年第一季度，我們都會花費大量精力與客戶、HCP 和藥局合作解決這個問題。但我們能夠在推動新患者就診的同時做到這一點。

And I really do think it's the tangible benefit of the expanded team, not just more people but also the new hires becoming more proficient in driving diagnosis and treatment with INGREZZA. So I'd say, right on schedule, feeling really good about the expanded team. And as we said earlier, we do expect to see accelerated growth for the balance of the year, as we've reiterated with our guidance.

我確實認為這是擴大團隊帶來的實際好處，不僅僅是人員增多，新員工在使用 INGREZZA 進行診斷和治療方面也變得更加熟練。所以我想說，一切正如計劃所料，我對擴大後的團隊感到非常滿意。正如我們之前所說，我們確實預計今年餘下時間的成長將會加速，正如我們在指導中重申的那樣。

Maybe just to add to that real quickly, eight years in the launch and to think we just had our greatest quarter in terms of new patient starts is phenomenal, and I do attribute that to the team and their ability to catch up quickly and work through a very challenging Q1.

也許只是為了快速補充這一點，在推出八年後，我們認為我們剛剛經歷了新患者開始數量方面最好的一個季度，這是驚人的，我確實將其歸功於團隊及其快速趕上並度過極具挑戰性的第一季度的能力。

Thank you.

謝謝。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

Hey, congrats to Eiry for all the amazing achievements that she's accomplished on behalf of patients. We have a question about the JOURNEY study of valbenazine for adjunctive treatment of schizophrenia. ClinicalTrials.gov shows a March 2025 completion date. So should we expect those results any day now? And then as a follow-up, can you talk about the learnings you expect to leverage from the JOURNEY study? How will you apply those learnings to next-gen VMAT2 inhibitors? And what, if any, occasions from the recent failure of Cobenfy in ATS? Thank you.

嘿，恭喜 Eiry 為了病人所取得的所有驚人成就。我們對使用伐貝那嗪輔助治療精神分裂症的 JOURNEY 研究有一個疑問。ClinicalTrials.gov 顯示完成日期為 2025 年 3 月。那麼我們現在是否應該期待這些結果呢？然後作為後續問題，您能談談您希望從 JOURNEY 研究中獲得哪些經驗教訓嗎？您將如何將這些知識應用於下一代 VMAT2 抑制劑？那麼，Cobenfy 最近在 ATS 中失敗的原因是什麼（如果有的話）？謝謝。

Yes. Thanks very much, Josh. Thanks for the kind words as well. I really appreciate that. And I think in terms of the JOURNEY study, yes, it's a very important study for us in terms of learning for the VMAT platform. And obviously, this is a must-win area for us, the biology. And so we're really interested in understanding what we'll learn from that trial.

是的。非常感謝，喬希。我也感謝您的善意言辭。我真的很感激。我認為就 JOURNEY 研究而言，是的，對於我們學習 VMAT 平台而言，這是一項非常重要的研究。顯然，對我們來說，生物學是一個必須贏的領域。因此，我們非常有興趣了解我們將從該試驗中了解到什麼。

We will be reading out the study in the near future. I mean we said somewhere around the middle of the year, and I think we're still on track from that, as you saw from ClinicalTrials.gov as well. And I think we're going to be interested in understanding the potential efficacy as it's measured by reduction in the PANSS total score. But we also have a lot of other functional endpoints and other subgroup analyses within that study, which are going to allow us to understand more about what type of patient within that population might respond best to the biology that's represented within VMAT2 inhibition.

我們將在不久的將來宣讀這項研究。我的意思是，我們說的是大約在今年年中，我認為我們仍然在按計劃進行，正如您從 ClinicalTrials.gov 上看到的那樣。我認為我們將有興趣了解其潛在功效，因為它是透過 PANSS 總分的減少來衡量的。但我們在該研究中還有很多其他功能終點和其他亞組分析，這將使我們能夠更多地了解該人群中哪種類型的患者可能對 VMAT2 抑制所代表的生物學反應最佳。

I also think -- just one brief comment on the recent Cobenfy study. As you know, there are no medications approved for the adjunctive treatment of schizophrenia currently. And I think that study showed us again the difficulty in performing clinical research in this area. I mean our take on that was it was a well-run study for a medication that has already been proven to be effective in the treatment of acute psychosis in Cobenfy.

我還認為——只是對最近的 Cobenfy 研究做一個簡短的評論。如您所知，目前尚無核准用於精神分裂症輔助治療的藥物。我認為這項研究再次向我們表明了在該領域進行臨床研究的困難。我的意思是，我們對此的看法是，這是一項運作良好的藥物研究，該藥物已被證明可有效治療 Cobenfy 中的急性精神病。

And so the inability to show an additional improvement in that setting, I think, reflects more on the nature of the clinical trials that are performed in this area and also some of the challenges there in this patient population.

因此，我認為，在這種情況下無法顯示出額外的改善，更多地反映了在該領域進行的臨床試驗的性質，以及該患者群體面臨的一些挑戰。

Just one thing to add in that regard because we have been asked. I know you didn't ask this, but we are asked, does that have any implication for us with respect to our '568 program? And it doesn't, in any way, dampen our interest and belief in the Phase III program that we have for '568 in acute psychosis. I think we're very confident in the Phase II data that we generated for the 20-milligram dose. I'm very pleased to have just started the Phase III program in that setting. I think I said your name wrong, Jay, I'm terribly sorry about that. But yes, and thanks again for the question.

由於我們被問到，因此我只想補充一點。我知道您沒有問這個問題，但是我們被問到，這對我們的‘568 計劃有什麼影響嗎？但這絲毫沒有削弱我們對 568 治療急性精神病的 III 期計劃的興趣和信心。我認為我們對 20 毫克劑量產生的 II 期數據非常有信心。我很高興能夠在這樣的環境下啟動第三階段計劃。我想我叫錯了你的名字，傑伊，對此我深感抱歉。是的，再次感謝您的提問。

No worries. Thank you, Eiry.

不用擔心。謝謝你，Eiry。

Cory Kasimov, Evercore.

科里·卡西莫夫（Cory Kasimov），Evercore。

Great. Good afternoon, guys. Let me add my congrats to Eiry on a great run at Neurocrine. So two questions on CRENESSITY for me, one really quick one. Is there any amount of -- is there a material amount of inventory stocking in the first quarter?

偉大的。大家下午好。讓我對 Eiry 在 Neurocrine 取得的出色成績表示祝賀。所以我有兩個關於 CRENESSITY 的問題，其中一個問題很快。第一季的庫存量有多少？

And then a second question, when could we expect to see longer-term CRENESSITY data from your ongoing Phase III open-label extension? And what endpoints do you believe could be positively impacted by longer-term androgen control? Thank you.

然後是第二個問題，我們什麼時候可以看到您正在進行的 III 期開放標籤擴展的長期 CRENESSITY 數據？您認為長期雄性激素控制會對哪些終點產生正面影響？謝謝。

Hey, Cory, I love inventory questions. So there was very little -- there is very little stocking in the quarter from an inventory perspective. I'll let Eiry comment on planned upcoming data.

嘿，科里，我喜歡庫存問題。因此，從庫存角度來看，本季的庫存非常少。我會讓 Eiry 對計劃中即將發布的數據進行評論。

Yes. And just to remind everybody, the -- more than 90% of the patients in the randomized trials of CRENESSITY rolled over into the open-label extensions both on the pediatric and the adult side. And the vast majority of the patients have remained in the study ever since then, over 90%. And so we are in the process of actually shutting down the US portion of the adult open-label extension study.

是的。需要提醒大家的是，CRENESSITY 隨機試驗中超過 90% 的患者轉入兒科和成人開放標籤擴展試驗。從那時起，絕大多數患者一直留在研究中，超過 90%。因此，我們實際上正在關閉美國成人開放標籤擴展研究的部分。

And those individuals will be rolling on to commercial product over the next few months. The pediatric study, we are keeping going because it's generating additional very important data for us. And obviously, we are continuing the studies outside the United States.

這些人將在接下來的幾個月內開始生產商業產品。我們正在繼續進行兒科研究，因為它為我們提供了額外的非常重要的數據。顯然，我們正在美國以外繼續進行研究。

With respect to the data from those studies, we will be releasing one year data on both androgen control, glucocorticoid levels and clinical endpoints, such as metabolic endpoints and other reproductive hormone-related endpoints over the coming months. The Endo meeting in July and most -- in the most -- the nearest future is this month at PES.

關於這些研究的數據，我們將在未來幾個月發布關於雄激素控制、糖皮質激素水平和臨床終點（如代謝終點和其他生殖激素相關終點）的一年數據。Endo 會議將於 7 月舉行，最快將於本月在 PES 舉行。

That's very helpful. Thank you.

這非常有幫助。謝謝。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

Good afternoon, everyone. Thank you for taking my question. Eiry, congratulations on your pending retirement. So maybe I'd also love to ask you a question, just from your comments on the '568 Phase III plans. It sounds like you wouldn't necessarily write off an opportunity for '568 in an adjunctive therapy setting.

大家下午好。感謝您回答我的問題。Eiry，恭喜您即將退休。因此，也許我還想問您一個問題，僅針對您對“568 第三階段計劃”的評論。聽起來你不一定會放棄在輔助治療環境中使用‘568’的機會。

So I'm just wondering, in over commercial light up, if you had a success Phase III study in that setting with Cobenfy failing. Is there a site design that you see that would be worth pursuing for '568. I'm not sure if you think the risperidone, some group analysis is a real factor if there's some other unique design you would think about pursuing.

所以我只是想知道，在商業照明方面，如果 Cobenfy 失敗，您是否在那種環境下成功進行了 III 期研究。您認為是否有一個網站設計值得為『568』所追求？我不確定您是否認為利培酮，如果您考慮追求其他一些獨特的設計，那麼一些群體分析是一個真正的因素。

Brian, this is Kyle. Maybe I'll start this question and then Eiry and I can tag team a bit on this. I think what we've seen from the early Cobenfy launch is that 78% of patients are taking the therapy from a monotherapy perspective. Maybe there's some overlap there as patients transition from one medicine to next, and there's some overlap of two medicines. But for the most part, it seems like it's used in a monotherapy type of setting.

布萊恩，這是凱爾。也許我會提出這個問題，然後 Eiry 和我可以就此進行一些小組討論。我認為，從早期 Cobenfy 上市以來，我們看到 78% 的患者是從單一療法的角度接受治療的。當患者從一種藥物轉換到另一種藥物時，可能會有一些重疊，兩種藥物之間也會存在一些重疊。但在大多數情況下，它似乎是在單一療法類型的環境中使用的。

So that would be kind of point number one. Number two is, I think what we've seen for Cobenfy from BMS and others that have worked in this space, we have our own data that we'll be having be available around first half of this year.

這就是第一點。第二，我認為我們已經從 BMS 和其他在該領域工作過的公司看到了 Cobenfy 的情況，我們有自己的數據，這些數據將在今年上半年左右提供。

ATS trials are extremely difficult to run. I think there's still a lot of learnings there that can be applied in and thought about for the future. That's why we're excited about running the study and seeing the results for valbenazine in this space, so we can get a feel for that.

ATS 試驗的運作極為困難。我認為還有很多值得學習的地方，可以應用於未來並思考。這就是為什麼我們很高興進行這項研究並看到 Valbenazine 在該領域的研究結果，這樣我們就可以對此有所了解。

And the learnings from that will be plowed back into our next-generation compounds. But when it comes to the muscarinic themselves, we think that there is a significantly large opportunity standalone with the acute studies that we have planned for the registrational program and then moving into other indications, in particular, later this year with '568 into bipolar mania. And that's our current strategy.

從中獲得的經驗教訓將會被運用到我們的下一代化合物中。但就毒蕈鹼類藥物本身而言，我們認為，我們為註冊計劃規劃的急性研究本身就蘊藏著巨大的機會，然後我們將轉向其他適應症，特別是今年晚些時候將推出的‘568’用於治療躁鬱症。這就是我們目前的策略。

Marc Goodman, Leerink Partners.

馬克古德曼（Marc Goodman），Leerink Partners。

Matt, with INGREZZA, you've talked about $5,800 as the ASP that we should be thinking about for this year. Obviously, that number has changed. If you could give us a sense of what the new number is. And then, Eiry, definitely, we'll all miss you. Maybe just a question for you. Excluding '568, can you talk about the rest of the muscarinic portfolio and where we are? Thanks.

馬特，在 INGREZZA，您談到我們今年應該考慮的平均售價為 5,800 美元。顯然，這個數字已經改變了。請告訴我們新的數字是多少。然後，Eiry，我們肯定會想念你的。也許這只是一個問題。除了 568 之外，您能談談其餘的毒蕈鹼產品組合以及我們目前的情況嗎？謝謝。

Yes. Marc, I think I've gotten away from getting into the nuances of the exact net revenue per script for a handful of quarters now. But I guess the guidance that I would give you is you typically see an improvement in gross to net going from Q1 to Q2. I would expect that to be sequentially down just slightly. And so I think that's the color that I would provide on net revenue per script, Marc. Go ahead, Eiry.

是的。馬克，我認為我已經不再深入研究幾個季度以來每個腳本的確切淨收入的細微差別了。但我想我給你的指導是，你通常會看到從第一季到第二季的毛利率與淨利率有所改善。我預計這一數字將環比略有下降。所以我認為這就是我提供的每部劇本淨收入的詳細信息，馬克。繼續吧，Eiry。

Oh, thanks. And thanks, Marc. On the remainder of the muscarinic portfolio, just to remind you, we have '570, which is a dual M1/M4 agonist; '569, which is an M4-preferring agonist; and '567, which is an M1-preferring agonist; and then our own internally discovered '986, which is an M4 antagonist as a potential treatment for dystonias and Parkinson's tremor.

噢，謝謝。謝謝你，馬克。關於毒蕈鹼類藥物組合的其餘部分，需要提醒您的是，我們有 '570，它是一種雙重 M1/M4 激動劑；'569，它是一種 M4 優先激動劑；'567，它是一種 M1 優先激動劑；然後是我們自己內部發現的 '986，它是一種 M44 拮抗劑，可用於帕金森氏震張和肌顫。

With respect to the agonists, I'm actually including the M4 antagonist as well, all of those medicines are progressing currently through Phase I studies. For '570, we will be completing Phase I in the very near future and starting a Phase II study by the end of this year in acute psychosis.

關於激動劑，我實際上也包括 M4 拮抗劑，所有這些藥物目前都在進行 I 期研究。對於 570，我們將在不久的將來完成第一階段，並在今年年底前開始針對急性精神病的第二階段研究。

And that will be the next Phase II start for us from that platform. And then as '569 and '567 complete their Phase I studies, we'll be talking more about that and the potential next steps there, including any potential Phase II starts in the foreseeable future.

這將是我們從這個平台開始的下一個第二階段。然後，隨著 569 和 567 完成其第一階段的研究，我們將更多地討論這一點以及潛在的後續步驟，包括在可預見的未來開始的任何潛在的第二階段。

Thanks.

謝謝。

Sean Laaman, Morgan Stanley.

摩根士丹利的肖恩拉曼。

This is Mike Riad on for Sean Laaman. A big congrats to Eiry for all the impact you made. Thinking about INGREZZA, Teva's set of guidance suggests a good amount of patients can come yet this year. But the data that was presented at AMCP, so how patients don't reach that therapeutic dose on AUSTEDA XR. So thinking about that, how do you see the AUSTEDA drop-off market evolving? And do you think that some proportion of those drop-offs can switch to INGREZZA and help the patient starts? Thanks.

我是肖恩·拉曼 (Sean Laaman) 的邁克·裡亞德 (Mike Riad)。熱烈祝賀 Eiry 所做的巨大貢獻。考慮到 INGREZZA，Teva 的指導表明今年仍將有大量患者可以就診。但是 AMCP 上展示的數據表明，患者服用 AUSTEDA XR 後為何無法達到治療劑量。那麼考慮到這一點，您如何看待 AUSTEDA 下車市場的發展？您是否認為這些下降的部分患者可以改用 INGREZZA 並幫助患者開始復原？謝謝。

We were very encouraged by the information that we recently published regarding the therapeutic dosing. And I'd just remind you that, obviously, with the 40 milligram and 80 milligram start dosing at a therapeutic dose level and continues throughout the patient's period of time on the medicine.

我們最近發布的有關治療劑量的資訊令我們感到非常鼓舞。我只是想提醒你，顯然，40 毫克和 80 毫克的劑量以治療劑量開始，並在患者服藥的整個期間持續服用。

And so from that point of view, I think, as Eric alluded to in his prepared remarks as well, I think we have a very high confidence level in the value that INGREZZA can bring to patients. It's, as we said, highly effective, including in the data that we recently published on long-term data in more elderly population as well, uniquely selective in terms of its VMAT2 inhibition. And we have the broader set of data that we believe in patient populations that can experience value. And so we're focused on that and continuing to educate around that.

因此，從這個角度來看，我認為，正如 Eric 在他的準備好的發言中提到的那樣，我認為我們對 INGREZZA 能為患者帶來的價值非常有信心。正如我們所說，它非常有效，包括我們最近發布的針對更多老年族群的長期數據，其在 VMAT2 抑制方面具有獨特的選擇性。我們擁有更廣泛的數據，我們相信患者群體能夠感受到價值。因此，我們專注於此並繼續圍繞此開展教育。

The only thing I would add, just to piggyback here, is that the majority of patients that we see starting on INGREZZA have been and continue to be newly diagnosed and really treated. There isn't a lot of switching that happens in the VMAT2 market, and we haven't seen that dynamic really change that much over time. So we continue to make progress with diagnosis and motivating treatment. But for the most part, the patients that are starting INGREZZA are getting started on the VMAT2 for the first time.

我唯一想補充的是，我們觀察到大多數開始使用 INGREZZA 的患者都已經並將繼續接受新的診斷和治療。VMAT2 市場中並沒有發生太多的轉換，而且我們也沒有看到這種動態隨著時間的推移而發生太大的變化。因此，我們在診斷和激勵治療方面不斷取得進展。但大多數情況下，開始使用 INGREZZA 的患者都是第一次使用 VMAT2。

I appreciate that. Thanks.

我很感激。謝謝。

Ash Verma, UBS.

瑞銀的 Ash Verma。

Congrats from my side as well. Just on INGREZZA, maybe can you talk about any pull-through on these new contracting or the Medicare Part D formulary access that you mentioned? When does that happen? Like did that benefit 1Q? Or is that more of a 2Q or later in the year? And just secondly, what was the percentage increase in the sales force footprint, if you can remind us? And when do you expect that benefit to start to accrue? Thanks.

我本人也對此表示祝賀。就在 INGREZZA 上，您能否談談您提到的這些新合約或 Medicare D 部分處方集訪問的任何進展？那是什麼時候發生的？這對 1Q 有什麼好處嗎？或者這更像是第二季或今年晚些時候的事情？其次，如果您能提醒我們的話，銷售人員足跡的成長百分比是多少？您預計何時開始產生這種效益？謝謝。

Yes. I got the first part of your question in terms of the pull-through effort. Can you repeat the second part?

是的。我明白你關於拉動努力的問題的第一部分。你能重複一下第二部分嗎？

Yes. Like what was the percentage increase in the sales force footprint? And when do you expect that benefit to start to accrue?

是的。例如銷售人員足跡的增加百分比是多少？您預計何時開始產生這種效益？

Okay. Well, I'll take on the second part first. We didn't give exact head count numbers when we did the expansion in Q4 of last year, but it was a substantial increase of our psychiatry footprint. And as I mentioned before, we do think that it is starting to see tangible benefits here in the market primarily manifest as the record number of new patient starts we saw in Q1.

好的。嗯，我先處理第二部分。當我們在去年第四季進行擴張時，我們沒有給出確切的員工人數，但這是我們精神病學業務規模的大幅成長。正如我之前提到的，我們確實認為它開始在市場上看到切實的利益，主要反映為我們在第一季看到的新患者數量創紀錄。

With regards to pull-through, yes, certainly, our plan of action has always been when we have a formulary win, we attempt to pull it through. And the way that, that translate is certainly through personal and nonpersonal promotion. Our sales teams are aware of where there's been an add of INGREZZA on to a formulary. They're aware of the HCPs that are having more patients underneath that plan, and they're sure to communicate those changes.

關於堅持，是的，當然，我們的行動計劃一直是，當我們獲得處方勝利時，我們會嘗試堅持下去。而這種轉化的方式當然是透過個人和非個人的推廣。我們的銷售團隊知道在處方集中哪裡添加了 INGREZZA。他們知道該計劃下的醫療保健專業人員 (HCP) 擁有更多的患者，並且他們一定會傳達這些變化。

And with regards to this most recent formulary win, that process has already started as of the beginning of April. So we're going to continue to leverage when we do have increases in formulary coverage. But the way to think about it is it really benefits new patient starts. Existing patients who are already on treatment under that plan, they're already covered. They have a certain number of authorized refills. It's the new patient starts where there's a little less headwinds because it's now on formulary. Thanks.

就最近這次處方集勝利而言，這一進程已於 4 月初啟動。因此，當處方集覆蓋範圍確實增加時，我們將繼續發揮槓桿作用。但想想看，這確實對新病人的開始有益。已經根據該計劃接受治療的現有患者已經受到保障。他們有一定數量的授權補充裝。對於新患者來說，由於藥物已列入處方集，因此遇到的阻力會小一些。謝謝。

But just to be clear on how the financials flow on this, we will take a more immediate hit to gross to net starting in Q2. And the benefit from the new patient additions, as Eric mentioned too, will accrete over time. So it typically takes two quarters, three quarters, four quarters to get to a place where you're ROI-positive. But it's something that, as we mentioned and as Kyle mentioned, strategically important for us to continue to be a major player in this market.

但為了清楚了解財務狀況如何，從第二季開始，我們的毛利將受到更直接的打擊。正如 Eric 所提到的那樣，新患者加入所帶來的好處將隨著時間的推移而增加。因此，通常需要兩個季度、三個季度、四個季度才能實現投資回報率為正。但正如我們和凱爾所提到的，這對我們繼續成為這個市場的主要參與者俱有戰略重要性。

Thanks.

謝謝。

Mohit Bansal, Wells Fargo.

富國銀行的 Mohit Bansal。

This is Carina on for Mohit. Congrats on the great quarter. First, I wanted to ask a clarification question on INGREZZA gross to net. I think previously, you guys have said that you would expect some tailwind from the lower phasing of rebate under Part D redesign. I was wondering if that was any bit of a factor this year.

這是 Carina 為 Mohit 表演的。恭喜本季取得如此出色的成績。首先，我想就 INGREZZA 總額與淨額的比例提出一個澄清問題。我認為之前你們曾說過，你們期望在 D 部分重新設計下，退稅的階段性降低會帶來一些順風。我想知道這是否是今年的一個因素。

And then wanted to ask on the Phase III program for '568. How are you thinking about the number of sites, any ex US sites? And then any other changes in how the studies will be run versus the Phase II beyond the election on just one dose? Thanks.

然後想詢問‘568’的第三階段計劃。您如何考慮站點的數量，有美國以外的站點嗎？那麼，除了僅使用一劑藥物進行選舉之外，與第二階段相比，研究的進行方式還有其他變化嗎？謝謝。

Yes. From the Med D design change on the mandatory rebates, that was a slight benefit, I'd call it, like 1%. And that was a tailwind entering into this year. But that will, of course, be more than absorbed by the incremental contracting, which really is what's going to drive continued growth in value for INGREZZA and for the company going forward. Eiry, do you want to comment on '568?

是的。從強制回饋的 Med D 設計變更來看，這是一個輕微的好處，我稱之為 1% 左右。這是進入今年以來的順風。但是，這當然會被增量合約所吸收，這才是真正推動 INGREZZA 和公司未來價值持續成長的動力。Eiry，你想評論一下‘568’嗎？

Yes. We'll obviously provide more information as we get the remaining studies within the program up and running. But just a couple of comments. The first study is a US only study for the Phase III. And as you mentioned, it is a single dose level of 20 milligrams 1:1 randomization with placebo. So very simple in design.

是的。隨著該計劃剩餘研究的啟動和運行，我們顯然會提供更多資訊。但我僅提出幾點意見。第一項研究是僅在美國進行的第三階段研究。正如您所提到的，它是 20 毫克的單劑量水平，與安慰劑 1:1 隨機分配。設計非常簡單。

And we are taking all the learnings that we achieved from the Phase II, which we can talk more about once the full program is up and running. The number of sites doesn't increase substantially, which I think is really important. Because if you remember, our Phase II was a study that was run over a number of sites and a relatively complex adaptive trial design. So we think the simplicity of the Phase III program that we've designed and are implementing will be beneficial for us moving forward.

我們正在吸取第二階段所取得的所有經驗教訓，一旦整個計劃啟動並運行，我們就可以進一步討論。站點數量沒有大幅增加，我認為這非常重要。因為如果您還記得的話，我們的第二階段是一項在多個地點進行的研究，並且採用了相對複雜的自適應試驗設計。因此，我們認為，我們設計和實施的第三階段計劃的簡單性將有利於我們未來的發展。

Myles Minter, William Blair.

邁爾斯·明特、威廉·布萊爾。

Thanks, and also my congratulations to Eiry as well for a great career there at Neurocrine. Just on osavampator, the two Phase III studies that are listed on clinicaltrials.gov, just wondering about the powering assumptions for those trials given the 200 patients seems on the smaller end from what we've seen from peer studies that have obviously had mixed results. And secondly, I think on Slide 6, it says you've initiated four Phase III studies. What are the other two?

謝謝，同時我也恭喜 Eiry 在 Neurocrine 取得了輝煌的職業生涯。僅就 osavampator 而言，clinicaltrials.gov 上列出了兩項 III 期研究，我只是想知道這些試驗的動力假設，因為有 200 名患者，從我們從顯然有混合結果的同行研究中看到的情況來看，這些試驗的樣本量似乎較小。其次，我認為投影片 6 上說您已經啟動了四項 III 期研究。另外兩個是什麼？

Yes. So thanks, Myles. A couple of questions there. Let me get to the number of studies, first of all. Within the registration package for osavampator, there are three key studies: the two short-term randomized placebo-controlled studies; and one longer-term open-label study, which is obviously essential to enable us to look at longer-term safety.

是的。所以謝謝你，邁爾斯。有幾個問題。首先，讓我來談談研究的數量。在 osavampator 的註冊包中，有三項關鍵研究：兩項短期隨機安慰劑對照研究；一項長期開放標籤研究，顯然對於我們研究長期安全性至關重要。

With respect to the powering and the subject number, this is a -- could be quite a long conversation, but let me make it short. We -- one of the things we worry most about in the context of major depressive disorder studies is a placebo effect and obviously the expectation bias.

關於供電和主題編號，這可能是一個相當長的對話，但請讓我長話短說。我們——在重度憂鬱症研究中，我們最擔心的事情之一是安慰劑效應，顯然還有期望偏差。

And there is also a large body of research that suggests that the larger the study gets beyond a number of around about 20, the increased likelihood of placebo response, and therefore, the increased likelihood of potentially failed studies.

大量研究表明，研究規模越大（超過 20 左右），安慰劑反應的可能性就越大，因此研究失敗的可能性就越大。

So whilst the -- each of the Phase III studies is adequately powered and appropriately powered to measure an effect size significantly smaller than that which we saw in Phase II, highly confident in the size of the study, we have limited the size of the studies because of our take on understanding of the research in this area about the balancing act between increased subject numbers driving increased placebo response and increased risk of failed study.

因此，儘管每項 III 期研究都具有足夠的功效，能夠測量出比我們在第二期研究中看到的顯著更小的效應大小，並且對研究規模非常有信心，但我們還是限制了研究規模，因為我們對該領域研究的理解在於，增加受試者數量會導致安慰劑反應增加，而增加研究失敗的風險則會導致平衡。

Thanks for the questions.

感謝您的提問。

Laura Chico, Wedbush.

勞拉·奇科，韋德布希。

Good afternoon. I just wanted to revisit real quick on the INGREZZA patient numbers, and congrats on the record adds here. I'm not sure if you could also comment a little bit more about persistency and discontinuation rates.

午安.我只是想快速回顧一下 INGREZZA 患者人數，並祝賀這裡的記錄增加。我不確定您是否可以對持久性和中斷率發表更多評論。

I think, Eric, you mentioned the reauthorization was challenging. But are there differences in the duration of treatment depending on the channel from which patients are originating, say, long-term care versus psych? And then separately, I'm just curious with the R&D Day in the second half here, any highlights to share in terms of how is should be thinking about the potential focus of the event? Thank you.

艾瑞克，我認為你提到重新授權很有挑戰性。但是，根據患者的治療管道不同（例如長期照護和精神病治療），治療持續時間是否有差異？另外，我很好奇，對於下半年的研發日，有什麼亮點可以分享嗎？關於應該如何考慮此次活動的潛在焦點？謝謝。

Yes. With regards to the question around patient persistency, generally, it's been very steady from the early days of the launch through the most recent cut that we looked at. And we haven't seen any real differences in persistency across the different channels, whether the patient is being treated by a psychiatrist and neurologist or more recently coming in through long-term care.

是的。關於患者堅持度的問題，總體而言，從發布初期到我們看到的最新削減，患者堅持一直非常穩定。而且，我們並沒有看到不同管道在堅持方面有任何真正的差異，無論患者是由精神科醫生和神經科醫生治療，還是最近透過長期照護進行治療。

I did comment that this was a challenging Q1, a little bit more challenging perhaps than we've seen in years past. Anecdotally, feedback from the customers was that the reauthorization process was a bit more challenging from their perspective, and we saw slightly higher drop-offs in delayed refills versus prior years.

我確實評論說，這是一個充滿挑戰的第一季度，可能比過去幾年所經歷的更具挑戰性。有趣的是，客戶的回饋是，從他們的角度來看，重新授權過程更具挑戰性，與前幾年相比，我們發現延遲補充的下降幅度略高。

All of that was counterbalanced by the record number of new patient adds. And so that's really what gives us the sort of the confidence and conviction in the acceleration of our growth given the uptake that we saw with new patients in Q1. But overall, no, we're not seeing any real differences in patient persistency by segment.

所有這些都被創紀錄的新患者數量所抵消。因此，考慮到我們在第一季看到新患者的成長，這確實給了我們信心和信念，讓我們相信我們的成長將會加速。但總體而言，我們並沒有看到不同群體的患者堅持程度有任何真正的差異。

And this does conclude the question-and-answer portion of our call. I would now like to turn it back to Kyle Gano for any additional or closing remarks.

我們的電話問答部分到此結束。現在我想把演講時間交還給凱爾·加諾 (Kyle Gano)，請他發表補充意見或結束語。

Thanks, everyone. I know we didn't get to all of your questions. For those of you that missed, we'll be following up with you individually. But thanks, everyone, for joining this afternoon. As you can see, we made meaningful progress across several critical priorities of the business when we think about INGREZZA, reaccelerating new patient starts, improving access for health care providers and the patients they serve, successfully launching CRENESSITY and initiating multiple Phase III studies.

謝謝大家。我知道我們沒有回答您的所有問題。對於那些錯過的人，我們將單獨與您聯繫。但感謝大家今天下午的參與。正如您所看到的，當我們考慮 INGREZZA 時，我們在業務的幾個關鍵優先事項上取得了有意義的進展，重新加速新患者的開始，改善醫療保健提供者及其服務的患者的機會，成功推出 CRENESSITY 並啟動多個 III 期研究。

Neurocrine has never been in a stronger position, and we'll continue to remain focused on execution and evolution of the pipeline as we move through the remainder of the year. So looking forward to seeing all at the upcoming conferences or on your latest Zoom call. So looking forward to speaking with you soon. Thanks so much.

Neurocrine 的地位從未如此強大，在今年剩餘時間裡，我們將繼續專注於產品線的執行和發展。因此，期待在即將召開的會議或最新的 Zoom 會議上見到大家。期待很快與您交談。非常感謝。

This does conclude today's program. Thank you for your participation. You may disconnect at any time, and have a wonderful rest of your day

今天的節目到此結束。感謝您的參與。您可以隨時斷開連接，享受美好的一天