Neurocrine Biosciences Inc (NBIX) 2024 Q4 法說會逐字稿

Good day, everyone, and welcome to today's Neurocrine Biosciences reports Q4 and fiscal year 2024 Earnings Call. (Operator Instructions) Please note today's call will be recorded and I will be standing by should you need any assistance.

大家好，歡迎參加今天的 Neurocrine Biosciences 第四季和 2024 財政年度收益電話會議。（操作員指示）請注意，今天的通話將被錄音，如果您需要任何幫助，我將隨時待命。

It is now my pleasure to turn the conference over to Vice President of Investor Relations, Todd Tuschla.

現在我很高興將會議交給投資者關係副總裁 Todd Tuschla。

Thank you, and a good Thursday afternoon to everyone. Welcome to Neurocrine Biosciences' fourth quarter and full year 2024 earnings call. Joining me today are Kyle Gano, Chief Executive Officer; Matt Abernathy, Chief Financial Officer; Eric Benovich, Chief Commercial Officer; and Ivory Roberts, Chief Medical Officer.

謝謝大家，祝大家星期四下午愉快。歡迎參加 Neurocrine Biosciences 2024 年第四季和全年財報電話會議。今天與我一起的還有執行長 Kyle Gano； Matt Abernathy，財務長； Eric Benovich，首席商務長；以及首席醫療官 Ivory Roberts。

Hearing our 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. We'll go to Q&A after repair remarks, and as is our custom, and with your help, we will try to get to everyone's questions.

聽到我們的呼籲後，我們將做出前瞻性的聲明。這些聲明受某些風險和不確定性的影響，我們的實際結果可能存在重大差異。我鼓勵您查看我們最新的 SEC 文件中討論的風險因素。修復意見發表後，我們將進入問答環節，按照我們的慣例，在您的幫助下，我們會盡力解答每個人的問題。

At this point, I'll turn the call over to Kyle.

現在，我將把電話轉給凱爾。

Thanks, Todd. Good afternoon, everyone. Over the last several years, Neurocrine has evolved meaningfully across our entire enterprise, from research and development to commercialization. Our 2024 results demonstrate positive impacts from this evolution, and we are excited to build upon these successes. With four approved medicines coming from our own efforts, we entered 2025 as a fully integrated biopharmaceutical company that is strong, stable, and growing. We are prepared to take on industry challenges and capitalize on opportunities to continue to deliver patients and shareholders.

謝謝，托德。大家下午好。在過去的幾年裡，Neurocrine 在我們整個企業中，從研發到商業化都取得了有意義的發展。我們的 2024 年業績證明了這一演變帶來的正面影響，我們很高興能夠在這些成功的基礎上再接再厲。憑藉我們自身努力獲得的四種核准藥物，我們將在2025年成為一家強大、穩定且不斷發展的全面整合的生物製藥公司。我們準備迎接產業挑戰，並抓住機會繼續為患者和股東提供服務。

From a commercial perspective, INGREZZA continues to set the standard. Eight years after introducing the first treatment for tardive dyskinesia, we're on track to once again achieve double-digit year-over-year growth this year. Where our guidance reflects a moderated growth rate relative to 2024, which was our all-time highest growth year, we are focused on all opportunities to continue to maximize the potential of INGREZZA and its impact on patients.

從商業角度來看，INGREZZA 繼續制定標準。在推出首個治療遲發性運動障礙的藥物八年後，我們今年預計將再次實現兩位數的年成長。我們的指引反映了相對於 2024 年（我們歷史上成長最高的一年）的適度成長率，我們專注於所有機會，繼續最大限度地發揮 INGREZZA 的潛力及其對患者的影響。

From a big picture perspective, INGREZZA's differentiated profile in TD and HD chorea will enable us to do just that. INGREZZA has advantages, such as unsurpassed efficacy, the absence of complex titration, a novel sprinkle formulation for patients with difficulty swallowing, and advantages in certain sensitive patient populations, such as those that are apathetically impaired. This strong, clinically differentiated foundation ensures our ability to help many more patients.

從總體來看，INGREZZA 在 TD 和 HD 舞蹈病方面的差異化優勢將使我們能夠做到這一點。INGREZZA 具有許多優勢，例如療效無與倫比、無需複雜的滴定方法、針對吞嚥困難患者的新型噴灑配方，以及對某些敏感患者群體（例如冷漠症患者）的優勢。這種強大的、臨床差異化的基礎確保我們能夠幫助更多的患者。

When combined with our expanded and enhanced sales organization, which was rolled out in the last quarter, we are now better positioned than ever to meet the needs of approximately 90% of 800,000 tardive dyskinesia patients in the US who remain currently untreated with the VMAT2 inhibitor.

結合我們上個季度推出的擴大和增強的銷售組織，我們現在比以往任何時候都更有能力滿足美國 80 萬名目前未接受 VMAT2 抑制劑治療的遲發性運動障礙患者中約 90% 的需求。

Just as INGREZZA's transformed the standard of care for TD patients, we anticipate chronicity will do the same for people living with classical congenital adrenal hyperplasia. As a reminder, CRENESSITY is the first medicine specifically designed and developed for the CH patient community and the first new treatment option in over 70 years. Launching a groundbreaking new treatment is not without challenges, but over time, we believe CRENESSITY has the potential to be nerve and second blockbuster therapy.

正如 INGREZZA 改變了 TD 患者的照護標準一樣，我們預期慢性病也會對患有典型先天性腎上腺增生症的人產生同樣的影響。需要提醒的是，CRENESSITY 是第一種專門為 CH 患者群體設計和開發的藥物，也是 70 多年來第一種新的治療選擇。推出一項突破性的新療法並非沒有挑戰，但隨著時間的推移，我們相信 CRENESSITY 有潛力成為神經和第二個重磅療法。

Looking at launch cadence, we anticipate growth for CRENESSITY will initially be measured. But as a first-in-class, best-in-class medicine for patients, we are confident in its ramp-up and long-term growth potential. We look forward to leveraging CRENESSITY to diversify Neurocrine's revenue profile and drive near and long-term sales growth.

從發射節奏來看，我們預計 CRENESSITY 的成長將首先得到衡量。但作為患者首創、一流的藥物，我們對其發展和長期成長潛力充滿信心。我們期待利用 CRENESSITY 來實現 Neurocrine 的收入結構多樣化，並推動近期和長期銷售成長。

Turning now to research and development. In 2025, we will address new therapeutic areas, advance new modalities, specifically biologics, and improve productivity, and ultimately establish the foundation of what we expect to become a sustainable, internal R&D engine of innovation. Importantly, we will expect this enhanced productivity to deliver on average a new commercial launch every two years at study state.

現在轉向研究和開發。2025年，我們將針對新的治療領域，推動新的治療模式，特別是生物製劑，提高生產力，並最終奠定我們期望成為可持續的內部研發創新引擎的基礎。重要的是，我們預計，在研究狀態下，這種提高的生產力將平均每兩年帶來一次新的商業發布。

Starting this year alone, we anticipate our clinical stage pipeline will grow from 12 to 18 programs by year end, which will represent the most broad and robust neuroscience pipeline in the biopharma industry. Importantly, we will initiate multiple Phase 3 programs this year with Osavampator and major depressive disorder, and NBI-'568 in schizophrenia, both of which have the potential to further transform Neurocrine and drive significant growth at the end of this decade and into the next.

僅從今年開始，我們預計到年底我們的臨床階段產品線將從 12 個增加到 18 個，這將成為生物製藥行業最廣泛、最強大的神經科學產品線。重要的是，我們今年將啟動多個 3 期項目，包括用於治療重度憂鬱症的 Osavampator 和用於治療精神分裂症的 NBI-'568，這兩個項目都有可能進一步改變 Neurocrine，並推動本世紀末及下一個十年的顯著增長。

As we enter this year with a strong foundation, Neurocrine is well positioned for sustaining near and long-term growth. And is well on its way to becoming leading neuroscience company.

由於我們今年打下了堅實的基礎，Neurocrine 已準備好維持近期和長期的成長。並且正在穩步成為領先的神經科學公司。

With that, I'll turn things over to Matt.

說完這些，我會把事情交給馬特。

Thanks, Kyle. 2024 was a tremendous year for Neurocrine, with record sales growth for INGREZZA, positive Phase 2 data for both the Muscarinic, M4; and AMPA programs; and last but not least, the approval and launch of CRENESSITY. These achievements meant a strong foundation for Neurocrine's future success.

謝謝，凱爾。 2024 年對 Neurocrine 來說是豐收的一年，INGREZZA 的銷售成長創下了歷史新高，Muscarinic、M4 的 2 期數據也取得了積極的進展；和 AMPA 計劃；最後但同樣重要的一點是，CRENESSITY 的批准和推出。這些成就為 Neurocrine 未來的成功奠定了堅實的基礎。

In 2025, we anticipate INGREZZA's sales to be $2.5 billion to $2.6 billion, reflecting $250 million of growth at the midpoint of the range. While the guidance range reflects good dollar growth, we saw increased competitive pressure, as well as increased utilization management by payers over the course of 2024. This led to a slower growth trajectory heading into 2025.

2025 年，我們預計 INGREZZA 的銷售額將達到 25 億至 26 億美元，中間值成長 2.5 億美元。雖然指導範圍反映了良好的美元成長，但我們看到競爭壓力加大，以及 2024 年付款人的利用率管理加強。這導致2025年的成長軌跡放緩。

We are taking proactive steps to address this, including efforts to further develop and educate the TD market. We're still approximately 9 of 10 TD patients are not currently being treated with VMAT2 inhibitor, as well as efforts to drive future sales growth; most notably, the recent salesforce expansion in Q4 last year, which we expect will have a full impact in the second half of 2025 and beyond.

我們正在採取積極措施解決這一問題，包括努力進一步開發和教育 TD 市場。我們目前仍有約 90% 的 TD 患者未接受 VMAT2 抑制劑治療，並努力推動未來的銷售成長；最值得注意的是，去年第四季的銷售團隊擴張，我們預計這將在 2025 年下半年及以後產生全面影響。

Turning to CRENESSITY, although not providing an annual guide, we do wanna provide a few thoughts as you develop your financial models for 2025. We expect CRENESSITY to be a blockbuster medicine, helping many patients with classic CAH, but early revenues are expected to be measured, primarily due to three factors.

談到 CRENESSITY，雖然我們不提供年度指南，但我們確實想在您制定 2025 年財務模型時提供一些想法。我們預計 CRENESSITY 將成為一種轟動的藥物，幫助許多患有典型 CAH 的患者，但預計早期收入將難以衡量，主要歸因於三個因素。

First, the delayed timing of reimbursement for a new rare disease product. Second, the frequency of patient flow into offices. And third, the trialing that will naturally occur as clinicians obtain real-world experience with a novel medicine like CRENESSITY. One additional note on CRENESSITY, we did recognize $2 million in net sales in Q4 for initial bottle orders from our pharmacy partner in late December.

首先，新型罕見疾病產品的報銷時間延遲。第二，病人進出診間的頻率。第三，當臨床醫生獲得使用 CRENESSITY 等新藥的實際經驗時，試驗會自然發生。關於 CRENESSITY 的另外一點說明，我們確實在 12 月底從我們的藥房合作夥伴處獲得了第四季度 200 萬美元的首批瓶裝訂單的淨銷售額。

To close, a few comments on our investment profile. We continue to align our operating expenses with our top two capital allocation priorities, which are, number one, drive revenue growth; and number two, advance our R&D programs.

最後，我想就我們的投資概況發表幾點評論。我們繼續將我們的營運費用與我們的兩大資本配置重點保持一致，第一，推動收入成長；第二，推動我們的研發項目。

Our 2025 SG&A operating expense reflects a year of investment behind the CRENESSITY launch, and also the expanded INGREZZA salesforce.

我們 2025 年的銷售、一般及行政開支反映了 CRENESSITY 推出後一年的投資，以及擴大 INGREZZA 銷售隊伍的投資。

For R&D, the increased investment in 2025 aligns with our previous guide reflecting the initiation of our two major psychiatry programs advancing into Phase 3, with Neurocrine now fully funding the Osavampator program. Please note, we included $60 million of development milestones in R&D, including $35 million for Takeda and $15 million for Nxera associated with the initiation of our Phase 3 programs. If other future development milestones are achieved, we will update our OPEx guide as appropriate.

對於研發，2025 年的投資增加與我們先前的指南一致，反映了我們兩個主要精神病學計畫啟動並進入第 3 階段，其中 Neurocrine 現在全額資助 Osavampator 計畫。請注意，我們在研發中納入了 6000 萬美元的開發里程碑資金，其中包括用於武田的 3500 萬美元和用於 Nxera 的 1500 萬美元，這些資金均與我們第 3 階段項目的啟動有關。如果未來實現其他發展里程碑，我們將適當更新我們的 OPEx 指南。

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

現在，我將電話交給我們的首席商務官 Eric Benavich。埃里克？

Thanks, Matt. 2025 marks an important year of transformation and execution for our commercial organization. With the recent launch of CRENESSITY, we have the opportunity to raise the standard of care for the congenital adrenal hyperplasia community and to add an important second growth driver to Neurocrine's commercial portfolio.

謝謝，馬特。 2025年是我們商業組織轉型和執行的重要一年。隨著 CRENESSITY 的近期推出，我們有機會提高先天性腎上腺增生症群體的護理標準，並為 Neurocrine 的商業組合增加重要的第二個成長動力。

Before I provide further insight on CRENESSITY, I want to take a moment to highlight that 2024 was an all-time record growth year for INGREZZA, increasing annual sales by approximately $475 million, driven by increased volume, continued strong compliance, and improvement in growth-to-net dynamics. Even with this record performance, as Matt highlighted, we still have a tremendous opportunity ahead for our INGREZZA franchise. With approximately 800,000 people in the US suffering from TD and less than 10% of them currently being treated with VMAT2 inhibitors, we foresee substantial growth potential in the years to come.

在我對 CRENESSITY 提供進一步的見解之前，我想花點時間強調一下，2024 年是 INGREZZA 創紀錄的增長年，年銷售額增長約 4.75 億美元，這得益於銷量增加、持續強勁的合規性以及淨增長動態的改善。即使取得了這樣的創紀錄的成績，正如馬特所強調的，我們的 INGREZZA 特許經營權仍然有巨大的發展機會。美國約有 80 萬人患有 TD，其中目前只有不到 10% 正在接受 VMAT2 抑制劑治療，我們預計未來幾年將具有巨大的成長潛力。

With last year's investment to expand the sales force, ongoing healthcare provider disease state education, and direct-to-consumer efforts, we expect continued growth in 2025 across the psychiatry, neurology, and long-term care segments of our business. Notably, healthcare provider turnover remains particularly high in psychiatry and long-term care settings.

透過去年擴大銷售團隊的投資、持續的醫療保健提供者疾病狀況教育以及直接面向消費者的努力，我們預計 2025 年我們業務的精神病學、神經病學和長期護理領域將繼續增長。值得注意的是，在精神病學和長期照護領域，醫療保健提供者的流動率仍然特別高。

Therefore, as in prior years, our commercial and medical teams continue to address the high unmet medical need for education and to motivate healthcare providers to screen, diagnose, and treat TD and Huntington's chorea patients.

因此，與往年一樣，我們的商業和醫療團隊繼續解決尚未滿足的醫療教育需求，並激勵醫療保健提供者對 TD 和亨廷頓舞蹈症患者進行篩檢、診斷和治療。

Our 2025 INGREZZA sales guidance range of $2.5 billion to $2.6 billion contemplates the continuing growth of the VMAT2 class across, tardive dyskinesia and Huntington's chorea, and takes into account key external factors, like the increasingly complex payer environment and competitive dynamics.

我們對 2025 年 INGREZZA 銷售預期範圍為 25 億至 26 億美元，考慮到了 VMAT2 類藥物在遲發性運動障礙和亨廷頓舞蹈症治療領域的持續增長，同時也考慮了關鍵的外部因素，例如日益複雜的付款人環境和競爭動態。

Looking beyond 2025 with INGREZZA's differentiated product profile, an expanded and talented team, and 13 remaining years of exclusivity, we expect to maintain our position as the leader in the VMAT2 market while we continue to develop the next generation of VMAT2 inhibitors.

展望 2025 年以後，憑藉 INGREZZA 的差異化產品組合、不斷壯大的優秀團隊以及剩餘 13 年的獨家經營權，我們期望在繼續開發下一代 VMAT2 抑製劑的同時，保持我們在 VMAT2 市場的領先地位。

So now turning to CRENESSITY. We were delighted with the early FDA approval in mid-December and the broad labeling for this first-in-class and first on disease medicine. Following approval, there is a significant level of enthusiasm and excitement across the endocrinology provider in CAH patient family communities.

現在轉向 CRENESSITY。我們很高興看到 FDA 在 12 月中旬提前批准了這一同類首創藥物以及首個用於治療疾病的藥物，並將其列為廣泛的適應症。在獲得批准後，CAH 患者家庭社區的內分泌科醫生表現出了相當程度的熱情和興奮。

Even though FDA approval came right before the holidays, we were pleased to receive 11 new patient start forms in the less than two full weeks before exiting 2024. As a brand-new medicine, CRENESSITY is starting out as a nonformulary drug across all health plans. Therefore, in the early phase of the launch, we expect the majority of patients starting CRENESSITY will initially be dispensed non-reimbursed prescriptions via our Quick Start program to get them going on treatment while reimbursement is being secured.

儘管 FDA 的批准是在假期前才發布的，但我們很高興在 2024 年結束前的不到兩週內收到了 11 份新患者的開始表格。作為一種全新的藥物，CRENESSITY 最初是作為所有健康計劃中的非處方藥。因此，在發布的早期階段，我們預計大多數開始使用 CRENESSITY 的患者將首先透過我們的快速啟動計劃獲得非報銷處方，以便在確保報銷的同時讓他們接受治療。

For each patient, our team, together with our specialty pharmacy partner, PANTHERx Rare. We'll work through their insurance companies process to secure reimbursement and transition them to commercial product. Ultimately, we expect CRENESSITY to be broadly reimbursed with the majority of patients paying $12 or less per month out of pocket. Long-term success with CRENESSITY will be driven by our ability to reach and educate the CAH community on this breakthrough medicine.

對於每位患者，我們的團隊與我們的專業藥房合作夥伴 PANTHERx Rare 一起工作。我們將透過他們的保險公司流程來確保報銷並將其轉變為商業產品。最終，我們預計 CRENESSITY 將獲得廣泛報銷，大多數患者每月自付費用為 12 美元或更少。CRENESSITY 的長期成功將取決於我們是否有能力接觸 CAH 群體並向其普及這項突破性藥物。

We know from our experience with INGREZZA that this effort can take some time. There are no shortcuts when it comes to building new markets. Our field teams have a considerable number of appointments and programs booked in the coming months to educate endocrinologists on this exciting new medicine. We've long said CRENESSITY has all the hallmarks of our next blockbuster opportunity. It won't happen overnight, but we couldn't be more excited about its potential.

從我們與 INGREZZA 合作的經驗中我們知道，這項努力可能需要一些時間。開拓新市場沒有捷徑。我們的現場團隊在未來幾個月內已經預約了大量的預約和項目，以便對內分泌學家進行有關這種令人興奮的新藥物的教育。我們早就說過，CRENESSITY 具備我們下一個轟動作品的所有特徵。這不會在一夜之間發生，但我們對它的潛力感到無比興奮。

All in all, we're pleased with the receptivity to CRENESSITY from the CAH community and excited about the prospects to improve the standard of care for people living with classic congenital adrenal hyperplasia.

總而言之，我們很高興看到 CAH 社區對 CRENESSITY 的接受度，並對改善典型先天性腎上腺增生症患者護理標準的前景感到興奮。

So with that, I'll now hand it over to my colleague, Dr. Eiry Roberts.

因此，現在我將把發言權交給我的同事 Eiry Roberts 博士。

Thanks, Eric, and good afternoon to everyone. When I joined Neurocrine over seven years ago, INGREZZA has just received approval for the treatment of tardive dyskinesia and our pipeline reached just three programs.

謝謝，艾瑞克，祝大家下午好。七年多前，當我加入 Neurocrine 時，INGREZZA 剛剛獲得治療遲發性運動障礙的批准，我們的研發線僅有三個項目。

Over time, we have transformed into a vastly different organization today, and I could not be more proud of the significant progress we've made. Since 2018, perhaps there is no program more emblematic of this transformation than CRENESSITY. We were extremely pleased with the outcome of the FDA approval process and final labeling for CRENESSITY, many thanks to the regulatory clinical development and all other cross-functional team members who successfully steered the program through development from start to finish.

隨著時間的推移，我們如今已轉變為一個截然不同的組織，我為我們所取得的重大進步感到無比自豪。自 2018 年以來，或許沒有哪個項目比 CRENESSITY 更能像徵這種轉變。我們對 FDA 批准流程和 CRENESSITY 的最終標籤結果感到非常滿意，非常感謝監管臨床開發和所有其他跨職能團隊成員，他們從頭到尾成功指導該專案的開發。

With a strong label that includes impressive efficacy and tolerability data from the adult and pediatric registrational studies CRENESSITY has the opportunity to transform the treatment paradigm for patients with classic congenital adrenal hyperplasia.

憑藉強大的標籤，包括來自成人和兒科註冊研究的令人印象深刻的療效和耐受性數據，CRENESSITY 有機會改變經典先天性腎上腺增生患者的治療模式。

For over 70 years prior to CRENESSITY's approval, the only available treatment for CAH patients with lifelong treatment with glucocorticoids, usually at high superphysiologic doses. This fundamentally floored approach was the only option for patients and their doctors until CRENESSITY.

在 CRENESSITY 核准之前的 70 多年裡，CAH 患者唯一可用的治療方法是終生使用糖皮質激素治療，通常是超生理劑量。在 CRENESSITY 出現之前，這種從根本上解決問題的方法是患者及其醫生的唯一選擇。

CRENESSITY is the first and only approved nonsteroidal treatment for classic CAH that enables independent control of ACTH and androgens, creating the opportunity for endocrinologists to work with patients and their families to reduce glucocorticoid dose to more physiologic replacement levels.

CRENESSITY 是第一個也是唯一一個核准的用於治療經典 CAH 的非類固醇藥物，可以獨立控制促腎上腺皮質激素和雄激素，為內分泌科醫生與患者及其家人合作將糖皮質激素劑量降低到更符合生理替代水平創造了機會。

Since approval, our medical affairs field teams have been highly engaged with the endocrinology community, conducting extensive educational programs to support launch. Meanwhile, our critical development effort continues to generate valuable longer-term data from the ongoing open-label extension studies in adults and pediatrics, and to work towards the generation of clinical data in patients younger than four years old.

自從獲得批准以來，我們的醫療事務現場團隊一直與內分泌學界密切合作，進行廣泛的教育計畫以支持啟動。同時，我們關鍵的開發工作將繼續從正在進行的成人和兒科開放標籤擴展研究中產生有價值的長期數據，並致力於產生四歲以下患者的臨床數據。

In parallel, our health outcomes teams are focused on generating important data to characterize the burden of disease in CAH, while importing the value proposition of CRENESSITY as an effective treatment for patients with CAH. I will reiterate early feedback from KOLs and advocacy groups has been encouraging, as we bring this new treatment option to patients with great needs who are looking for a better choice.

同時，我們的健康結果團隊致力於產生重要數據來描述 CAH 的疾病負擔，同時引入 CRENESSITY 作為 CAH 患者有效治療方法的價值主張。我要重申，KOL 和倡導團體的早期回饋令人鼓舞，因為我們為有巨大需求並尋求更好選擇的患者帶來了這種新的治療選擇。

Turning to late-stage programs. Neurocrine's Phase 3 pipeline is also set to transform this year as we initiate multiple registrational studies starting with Osavampator, our AMPA potentiator, for the adjunctive treatment of major depressive disorder in adults.

轉向後期專案。Neurocrine 的 3 期產品線也將在今年發生轉變，因為我們將啟動多項註冊研究，首先是我們的 AMPA 增效劑 Osavampator，用於成人重度憂鬱症的輔助治療。

Last week, we announced the initiation of the first of three registrational studies of Osavampator in MDD. The remaining two Phase 3 studies will initiate in the months ahead. Separately, we will also initiate the registrational program for NBI-568 our M4 selective orthosteric agonist for the treatment of schizophrenia, following the recent successful end of Phase 2 meeting with the FDA. The positive Phase 2 results from last year's proof-of-concept study give us the confidence and conviction to rapidly advance this molecule into Phase 3 studies as well as to initiate a Phase 2 study in bipolar mania in the second half of this year.

上週，我們宣布啟動 Osavampator 在 MDD 領域的三項註冊研究中的第一項。其餘兩項第三階段研究將在未來幾個月內啟動。另外，在最近與 FDA 成功結束第 2 階段會議後，我們也將啟動用於治療精神分裂症的 M4 選擇性正構激動劑 NBI-568 的註冊計畫。去年概念驗證研究的第 2 階段的積極結果使我們有信心和信念迅速推進該分子進入第 3 階段研究，並在今年下半年啟動雙相情感障礙的第 2 階段研究。

Meanwhile, our early-stage masculine portfolio is progressing through healthy volunteer Phase 1 studies. And notably, we anticipate initiating a Phase 2 study for the dual M1/M4 agonists, NBI-570 in acute psychosis in the second half of this year.

同時，我們早期的男性產品組合正在透過健康志願者第一階段研究取得進展。值得注意的是，我們預計將在今年下半年啟動雙 M1/M4 激動劑 NBI-570 治療急性精神病的 2 期研究。

The early-stage pipeline continues to expand also with several programs set to advance into Phase1 studies this year. most recently with NBI-'355, a selective dual NAV1.2/1.6 antagonist in collaboration with Xenon Pharmaceuticals, as a potential treatment for epilepsy, which initiated earlier this week.

早期研發管線也不斷擴大，今年有多個計畫將進入第一階段研究。最近一次是與 Xenon Pharmaceuticals 合作開發的 NBI-'355，一種選擇性雙重 NAV1.2/1.6 拮抗劑，用於治療癲癇，該計畫於本週稍早啟動。

We also anticipate the Phase 1 study of NBI-'675 and internally developed next-generation VMAT2 inhibitor to begin this quarter as well.

我們也預計 NBI-'675 和內部開發的下一代 VMAT2 抑制劑的第 1 階段研究也將於本季開始。

Furthermore, our Chief Scientific Officer, Jude Onyia and his team have made tremendous progress with our preclinical portfolio of internally developed large molecules, including peptides and totes and gene therapies. As these molecules progress through GLP tox in the coming months, if successful, they set us up very well for additional potential first-in-man clinic entries later this year and into 2026.

此外，我們的首席科學官 Jude Onyia 和他的團隊在我們內部開發的大分子臨床前產品組合方面取得了巨大進展，包括勝肽和手提包以及基因療法。隨著這些分子在未來幾個月內通過 GLP 毒性試驗，如果成功的話，它們將為我們在今年稍後和 2026 年獲得更多潛在的首次人體臨床應用奠定良好的基礎。

In closing, we've built what we believe to be one of the broadest and deepest neuroscience-focused pipelines in the industry, and this is just the beginning.

最後，我們已經建立了我們認為是業內最廣泛、最深入的神經科學為重點的管道之一，而這只是一個開始。

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. Operator, I think we're ready to take questions now.

謝謝，Eiry。接線員，我想我們現在可以回答問題了。

(Operator Instructions) Phil Nadeau, TD Cowen.

(操作員指示) Phil Nadeau，TD Cowen。

Good afternoon. Thanks for taking our question. You've been very clear that you expect a measured launch for CRENESSITY in terms of revenue during the first half of this year. We've also guided to giving new start forms as you did today. There's a very vigorous debate among investors as to what is a good trajectory of new start forms and what isn't. I was curious if you people willing to provide any of Neurocrine's perspective on what pace of new start forms we should anticipate through the first half of this year and into the second half of 2025?

午安.感謝您回答我們的問題。您已經非常明確地表示，您預計 CRENESSITY 的收入將在今年上半年穩步提升。我們還指導您填寫新的開始表格，就像您今天所做的那樣。投資人之間就新創業形式的良好發展軌跡以及不良發展軌跡展開了激烈的爭論。我很好奇，你們是否願意從 Neurocrine 的角度提供一些關於今年上半年和 2025 年下半年我們應該預期新開始形式的速度？

Yeah. Thanks, Phil. This is Eric. So first off, just really pleased that we got an early approval last year -- late last year and at a great very broad label to work with. And obviously, it gave us an opportunity to get moving a little bit before the end of the year.

是的。謝謝，菲爾。這是埃里克。首先，我們非常高興我們在去年年底就獲得了早期批准，並且獲得了非常廣泛的合作範圍。顯然，這給了我們一個在年底前稍微採取行動的機會。

So those -- as we had said earlier this year at the JPMorgan conference, we would be providing updates each quarter on the prior quarters. Treatment forms that have come in. And that 11% represents just a few working days, frankly, before the turn of the year.

所以 — — 正如我們今年早些時候在摩根大通會議上所說的那樣，我們將在每個季度提供前幾季的更新資訊。已出現的治療形式。坦白說，這 11% 僅代表年初之前的幾個工作日。

We're really pleased with the early launch dynamics here. I'm really excited about the feedback that we're getting from providers. And I'm not going to comment specifically on what constitutes a good ramp. But so far, so good, and I'd say more than good in terms of the CRENESSITY launch dynamics.

我們對早期的發布動態感到非常滿意。我對於我們從供應商那裡得到的回饋感到非常興奮。我不會具體評論什麼是好的坡道。但到目前為止，一切都很好，而且我認為，就 CRENESSITY 發射動力而言，情況非常好。

Just a reminder, this is the first new medicine for these patients in over 70 years. So thinking about what the adoption curve might look like, Phil, it's really -- I think everybody is wanting to know what that would look like. But as Eric said, receptivity has been incredibly strong so far. And I think you probably sense that in all the market checks that you and the other investors too. So, so far, so good, but we're early in the launch, and I'm not going to claim a victory yet. And we'll share more detail in May.

需要提醒的是，這是 70 多年來第一種針對此類患者的新藥。因此，菲爾，想想採用曲線可能會是什麼樣子，這真的是——我想每個人都想知道它會是什麼樣子。但正如埃里克所說，到目前為止，接受度一直非常強烈。我想您可能在所有市場檢查中都感覺到了這一點，您和其他投資者也一樣。所以，到目前為止，一切都很好，但我們才剛開始，我還不准備宣布勝利。我們將在五月分享更多細節。

Thanks for taking our question.

感謝您回答我們的問題。

Paul Mattis, Stifel.

保羅馬蒂斯（Paul Mattis），斯蒂費爾（Stifel）。

Hey, thanks so much. I appreciate the question. Can you expound upon some driver guidance. I feel like looking at our model, I'm really confused because you grew 26%. The guide is less than 10% sequentially. And I know historically, you guys have given conservative guidance.

嘿，非常感謝。我很感謝你提出這個問題。能否詳細說明一些駕駛指南？我覺得看著我們的模型，我真的很困惑，因為你成長了 26%。該指引比上一季下降了 10%。我知道，從歷史上看，你們一直給予保守的指導。

You've done a great job of VMAT, but I'm just concerned, are you trying to send us a greater message here that this market is actually sort of changing going into 2025? Like what are you seeing during the quarter? And I'm wondering if the Street is just making something here, given that I think opens is above the high end. Thank you.

您在 VMAT 方面做得非常出色，但我只是擔心，您是否想向我們傳達一個更大的訊息，即這個市場實際上在 2025 年會發生某種變化？您在本季看到了什麼情況？我想知道華爾街是否只是在這裡做一些事情，因為我認為開盤價高於最高價。謝謝。

Yeah, I'll tackle that, Paul. So first of all, I just want to reiterate that it's amazing that seven years after the launch, that we had a record growth here for INGREZZA in 2024. And we're really proud about that.

是的，我會解決這個問題，保羅。首先，我想重申，推出七年後，INGREZZA 在 2024 年實現了創紀錄的成長，這真是令人驚訝。我們對此感到非常自豪。

And as I mentioned in my prepared remarks, our 2025 guidance of $2.5 billion to $2.6 billion reflects continued growth of the VMAT2 category and external factors such as an increasingly complex payer environment and competitive dynamics.

正如我在準備好的發言中提到的，我們 2025 年 25 億至 26 億美元的指導價格反映了 VMAT2 類別的持續增長以及付款人環境和競爭動態日益複雜的外部因素。

We're taking proactive steps to address the competition, including our recently expanded sales team and DTC. And historically, we've done really well in terms of access to reimbursement, and we're going to continue to provide excellent support to our customers in order to maximize their access to INGREZZA going forward.

我們正在採取積極措施來應對競爭，包括最近擴大的銷售團隊和 DTC。從歷史上看，我們在獲得報銷方面做得非常好，我們將繼續為客戶提供優質支持，以便最大限度地提高他們在未來獲得 INGREZZA 的機會。

With INGREZZA's differentiated product profile and expanded and talented team, a long runway of exclusivity and less than 10% of TD patients currently being treated with VMAT2 inhibitors, we really expect to see continued strong growth for INGREZZA 2025 and beyond.

憑藉 INGREZZA 的差異化產品組合、不斷擴大的優秀團隊、長期的獨佔性以及目前不到 10% 的 TD 患者正在使用 VMAT2 抑製劑治療，我們確實預計 INGREZZA 在 2025 年及以後將繼續保持強勁增長。

Maybe just to add to this is Kyle. We did have our sales force expansion in Q4, which always causes some disruption, and we expect that to pick up steam and help us into 2025 as we get longer into the year and certainly in subsequent years.

或許凱爾 (Kyle) 可以補充這一點。我們的銷售團隊在第四季度確實有所擴張，這總是會造成一些混亂，我們預計，隨著今年的到來以及隨後幾年的延長，這一趨勢將會加速並幫助我們進入 2025 年。

But on the growth potential, I think that we're ever more bullish on the opportunity for INGREZZA, starting with the differentiation over our other competitor in the space, the tetrabenazine. Starting with the first dose being efficacious dose, the efficacy profile that we have, the ability to present a new formulation for patients that have difficulty swallowing and advantages in certain patient populations.

但就成長潛力而言，我認為我們對 INGREZZA 的機會更加看好，首先就是與該領域的其他競爭對手丁苯那嗪的差異化。從第一劑有效劑量開始，我們擁有的功效概況，為吞嚥困難的患者提供新配方的能力以及在某些患者群體中的優勢。

In particular, those with hepatic pyramid, all the reasons to believe the continued growth in the product over time we appreciate there are some headwinds moving into this year, some of them having to do with us and the sales force expansion. But we're ever more excited about the opportunity that remains here. And the vast majority of patients still aren't being treated with the VMAT2 inhibitor.

特別是那些患有肝金字塔的人，所有理由都相信隨著時間的推移產品會持續增長，我們意識到今年會遇到一些阻力，其中一些與我們和銷售隊伍的擴張有關。但我們對這裡仍然存在的機會感到更加興奮。但絕大多數患者仍未接受 VMAT2 抑制劑治療。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Great. Thank you so much for taking my question. Mine is also on INGREZZA. Can you talk about general expectations for 1Q '25 maybe comparing that to prior 1Q, which was part of seasonality? I guess I'm more curious about it this year, just given expectations potentially for lowered revenue per script this year relative to 2024. Should we be thinking that you could have a decline on the quarter-on-quarter revenue this year? Thanks.

偉大的。非常感謝您回答我的問題。我也在 INGREZZA 上。您能否談談對 25 年第一季的整體預期，例如將其與之前的第一季進行比較，這是季節性的一部分？我想我今年對此更感興趣，因為預計今年每部劇本的收入可能會比 2024 年下降。我們是否應該認為今年的季度營收可能會下降？謝謝。

Yeah. Thanks, Tazeen. So I can't comment on the specifics of our inter-quarter performance. But typically, this is a challenging time of the year, due to the need to get our many continuing patients to reauthorize the refills in a timely manner. And our teams are really busy executing their plans and working with their ECP customers and with the dispensing pharmacies to minimize any treatment gaps, and of course, retain patients.

是的。謝謝，Tazeen。所以我無法評論我們季度間表現的具體情況。但通常情況下，這是一年中充滿挑戰的時刻，因為我們需要讓許多繼續就診的患者及時重新授權續藥。我們的團隊正忙於執行他們的計劃，並與他們的 ECP 客戶和配藥藥房合作，以盡量減少治療差距，當然，也留住患者。

As you know, Q1 is the quarter each year with the biggest gross to net impact due to commercial co-pay contribution and sets and incremental rebate agreements kicking in. I'll be able to provide a little bit more color on Q1 performance when we get to the Q1 earnings call. But this is typical for us to be working through all of these payer-related issues. And it's something that we've got better at each year over the course of the launch.

眾所周知，由於商業共同支付貢獻以及套裝和增量回扣協議的生效，第一季是每年毛利對淨利影響最大的季度。當我們召開第一季財報電話會議時，我將能夠提供更多關於第一季業績的詳細資訊。但對我們來說，解決所有這些與付款人相關的問題都是很正常的。在產品發布的過程中，我們每年都在不斷進步。

So to be clear, Tazeen, you mentioned net revenue per script year over year. I would just say that embedded in our guidance is an assumption that net revenue per script in 2025 is going to be very similar to what we saw in 2024. But sequentially, there is that headwind moving from Q4 into Q1, which is around 3%, call it, this year.

因此，需要明確的是，Tazeen，您提到了同比每個劇本的淨收入。我只想說，我們的指引中包含一項假設，即 2025 年每部劇本的淨收入將與 2024 年的水準非常相似。但連續來看，從第四季到第一季存在逆風，今年約為 3%。

The other item that I just flag is that I am keeping an eye on ordering patterns. The way that the calendar sets itself up at the end of the quarter, there may be a little bit of noise. So obviously, very hard to predict how folks will order. And we obviously don't influence that, but we flag it for you just in case it causes noise at the end of the quarter, but would largely net itself out through the rest of the year and wouldn't be unique to Neurocrine.

我剛剛標記的另一件事是我正在關注訂購模式。由於季度末日曆的設定方式可能會出現一些噪音。顯然，很難預測人們會如何訂購。顯然，我們不會對這一點產生影響，但我們會為您標記，以防它在季度末引起噪音，但它會在全年剩餘時間內基本自行消除，並且不會對 Neurocrine 造成獨特影響。

So a lot of moving parts here. I think our focus remains for TD is to just get more diagnosis, get new patients being generated, and our sales force is very hungry to be able to help in that regard.

這裡有很多活動部件。我認為我們對 TD 的關注重點仍然是獲得更多的診斷，吸引新的患者，而我們的銷售團隊非常渴望在這方面提供幫助。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞（Jefferies）。

Hi, thanks so much. A quick one on INGREZZA and then on CRENESSITY. Should we expect that 60-40 market share split holding up given the evolving payer dynamic between INGREZZA and OITO, your guide currently implies a 4% to 5% market share loss versus Teva's guide.

你好，非常感謝。快速討論一下 INGREZZA，然後討論一下 CRENESSITY。鑑於 INGREZZA 和 OITO 之間不斷變化的付款人動態，我們是否應該預期 60-40 的市場份額分配將保持不變，那麼您的指南目前意味著與 Teva 的指南相比，市場份額將損失 4% 到 5%。

And then your team's talked about physicians will likely need to see patients in person before prescribing them CRENESSITY. Some of our KOL work has suggested otherwise. How many of your new patient starts are done actually with telehealth? And how do you see that dynamic evolving over time?

然後，您的團隊談到的醫生可能需要親自探望患者，然後才能為他們開出 CRENESSITY。我們的一些 KOL 工作表明情況並非如此。實際上，有多少新患者是透過遠距醫療就診的？您認為這種動態會隨著時間的推移而發生怎樣的變化？

Maybe I'll start with the INGREZZA question. What we've seen over the past couple of years is great overall growth in the category. It appears that both brands are doing quite well here. I think what we will see and expect moving forward is that we continue to be the market leader and lead on the profile that we have with INGREZZA, which we think is quite differentiating.

也許我應該從 INGREZZA 問題開始。過去幾年來我們看到的是該類別整體上取得了巨大的成長。看來這兩個品牌在這裡的表現都相當不錯。我認為，我們在未來將看到並期待的是，我們將繼續成為市場領導者，並憑藉 INGREZZA 的形象保持領先地位，我們認為這是非常與眾不同的。

On that CRENESSITY piece, I'll let Eric chime in on that one.

關於那篇 CRENESSITY 文章，我會讓 Eric 發表看法。

Yeah. Certainly, I do think there are some endocrinologists that are prepared or comfortable to prescribe CRENESSITY remotely or virtually without necessarily an accompanying patient visit. But all the work that we've done leading up to the launch indicates that the majority of endocrinologists are going to want to see their patient first and have that conversation with them in person before they recommend treatment with CRENESSITY.

是的。當然，我確實認為有些內分泌學家願意或願意遠端或虛擬地開出 CRENESSITY 處方，而不一定需要病人陪同。但我們在推出之前所做的所有工作表明，大多數內分泌學家都希望先見到他們的病人，並親自與他們交談，然後才推薦使用 CRENESSITY 治療。

And given the fact that it's a new medication with a totally new mechanism of action, it's understandable. And then over time, I think as doctors get more experience, they get more comfortable and potentially start to initiate treatment without a patient visit corresponding.

鑑於這是一種具有全新作用機制的新藥物，這是可以理解的。隨著時間的推移，我認為醫生會獲得更多經驗，他們會變得更加自在，並有可能在沒有患者就診的情況下開始治療。

Cory Kasimov, Evercore.

科里·卡西莫夫（Cory Kasimov），Evercore。

Hey, guys. Thanks for taking my question. Wonder if you can provide additional detail on payer traction with CRENESSITY kind of feedback thus far? And how long you expect the free drug program might last? Thank you.

嘿，大家好。感謝您回答我的問題。想知道您是否可以提供有關迄今為止 CRENESSITY 反饋中付款人吸引力的更多詳細資訊？您預計免費藥物計劃將持續多久？謝謝。

Yeah. So we put a system in place to make sure that when patients get prescribed CRENESSITY that they can get on treatment pretty quickly. Coming out of the gate here with this launch, CRENESSITY is a brand-new medicine. It's not on any formularies yet. So the process is to go through a formulary exceptions process for each and every patient.

是的。因此，我們建立了一個系統來確保患者在獲得 CRENESSITY 處方後能夠很快得到治療。CRENESSITY 是此次推出的全新藥物。它還不在任何處方表上。因此，該過程將對每位患者進行處方例外處理。

In order to get people started while reimbursement is being secured, we do have a fast start program, which after about a week, if the prescription claim hasn't been approved yet, but health plan will ship free product to them to get them started. And the expectation is that early in the launch, most patients will require a month or possibly two months of free goods before they're able to transition over to reimbursed product.

為了讓人們能夠在獲得報銷的同時開始使用，我們有一個快速啟動計劃，大約一周後，如果處方索賠尚未獲得批准，但健康計劃將免費向他們發送產品以幫助他們開始使用。預計在推出初期，大多數患者將需要使用一個月或兩個月的免費產品，然後才能夠過渡到報銷產品。

In terms of feedback from the health plans, it's early days yet. What we're seeing is that, as expected, many of these patients are going on to the free goods program initially. But we have had some patients that have had their prescription claims reimbursed pretty quickly, and they've been able to start on commercial product right from the get-go.

就健康計劃的回饋而言，現在還為時過早。我們看到的情況是，正如預期的那樣，許多患者最初都參加了免費商品計劃。但我們的某些患者很快就得到了處方費用的報銷，並且他們能夠從一開始就開始使用商業產品。

So so far, so good. And as I said before, we're really pleased with the feedback that we're hearing from endocrinologists and feedback from the CAH community, and we're confident in our ability to get CRENESSITY reimbursed. And to make sure that it's accessible and affordable, we estimate that the majority of patients will pay less than $12 per month.

到目前為止，一切都很好。正如我之前所說，我們對從內分泌學家和 CAH 社區聽到的反饋感到非常高興，並且我們對獲得 CRENESSITY 報銷的能力充滿信心。為了確保治療費用低廉且方便患者，我們估計大多數患者每月支付的費用將少於 12 美元。

And Cory, just an example, we had a great win even yesterday. One of the major plans came out with a coverage policy that was very, I guess, friendly in terms of what it would require between being over the age of four, being confirmed diagnosed with CAH. And so I do think the plans understand the disease, the team is doing a really good job educating those plans. And so far, I'd say that things are positive. But we're only five weeks into launch. So a lot still to go, but early signs are very positive.

科里，舉個例子，我們昨天就取得了一場偉大的勝利。其中一項主要計劃推出了一項覆蓋政策，我認為這項政策對於年齡超過四歲並且被確診患有先天性腎上腺皮質增生症 (CAH) 的人群的要求非常友好。因此我確實認為這些計劃了解這種疾病，團隊在宣傳這些計劃方面做得非常好。到目前為止，我認為事情都是正面的。但我們距離發布才過去五週。雖然還有很多工作要做，但早期跡象非常積極。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Thanks. So you cited utilization management related to INGREZZA. Can you elaborate on what that's looking like? And how does that tie in to your competitors' behavior vis-a-vis payers. In other words, is your competitor getting more aggressive with payers in terms of positioning on plans?

謝謝。因此您引用了與 INGREZZA 相關的利用管理。能詳細解釋一下它是什麼樣子的嗎？這與您的競爭對手的付款人行為有何關聯？換句話說，您的競爭對手在計劃定位方面對付款人的態度是否更積極？

Yeah. So obviously, access and affordability are really high priorities for us at Neurocrine. And historically, we've done really well with high prescription dispense rates and most patients paying less than $10 out of pocket per month. And in terms of utilization management, that's something that evolves over the course of time. And what we saw, especially in the second half of last year, was that some of the plans were starting to tighten up their utilization management and really what that might look like, for example, is changing the PA criteria periodically.

是的。因此顯然，對於 Neurocrine 來說，可近性和可負擔性是首要考慮因素。從歷史上看，我們的處方藥配發率很高，大多數患者每月自付金額不到 10 美元，因此我們的表現非常出色。就利用率管理而言，這是隨著時間的推移而發展的。我們看到，特別是在去年下半年，一些計畫開始加強其使用率管理，例如，實際上可能是定期更改 PA 標準。

And so ultimately, we need to stay on top of that payer environment and how plans are managing INGREZZA on a plan-by-plan basis. We have a pretty sophisticated infrastructure to make sure that we're really maximizing access for our patients. We have field reimbursement specialists we utilize all the data that we have to make sure. And I should say that we also have a really good pharmacy network in place.

因此，最終我們需要密切關注付款人環境以及計劃如何逐個計劃地管理 INGREZZA。我們擁有相當先進的基礎設施，以確保最大限度地為患者提供醫療服務。我們有現場報銷專家，我們會利用所有數據來確保一切順利。我應該說我們也有一個非常好的藥房網絡。

So as I said in my prepared remarks, it's a complex payer environment. Payers continue to evolve in terms of how they're managing specialty drugs. And that's something that we expect to see going forward, and that's a factor in our guidance.

正如我在準備好的演講中所說，這是一個複雜的付款人環境。付款人對特種藥品的管理方式不斷進步。這是我們期望未來會發生的事情，也是我們指導的因素。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

This is actually Malcolm Kono for Anupam. So with regard to the INGREZZA guidance, can you talk a little bit about the levers of growth amongst the segments? Are you expecting outsized growth from any one of the three segments?

這實際上是 Anupam 的 Malcolm Kono。那麼，關於 INGREZZA 指引，您能否談談各部門之間的成長槓桿？您預期上述任何一個領域都會出現超額成長嗎？

Yes, Malcolm, maybe this is Kyle. I'll start the question. We generally see as growth still continue to come from the psychiatry segment. I think we also see good investment or return on investment from our expansion in LTC over the past couple of years and see that being a larger portion of the business as well, in combination with work and efforts in the neurology space. But I think largely still the growth opportunity remains in psychiatry.

是的，馬爾科姆，也許這是凱爾。我來開始提問。我們普遍認為，精神病學領域仍將持續成長。我認為，我們在過去幾年中在 LTC 領域的擴張也帶來了良好的投資或投資回報，並且結合我們在神經病學領域的工作和努力，這也將成為我們業務的重要組成部分。但我認為精神病學領域仍有很大的成長機會。

You know some of the headwinds there still involve telemedicine to turnover in the offices and the best way to tackle those is through keeping TD top of mind in those different groups that are using those different aspects of Telemedicine and the PPs as well. And the way to look at breaking through that is through having greater frequency of interaction. And that's where the sales force comes in for us. So in terms of growth overall in psychiatry, but it will come across the board in the segments that we're looking at in psychiatry, LTC and neurology.

您知道，那裡的一些阻力仍然涉及遠距醫療和辦公室的人員流動，而解決這些問題的最佳方法是讓使用遠距醫療和 PP 不同方面的不同群體始終將 TD 放在首位。突破這一問題的方法是透過增加互動頻率。這就是銷售隊伍發揮作用的地方。因此，就精神病學的整體發展而言，它將全面出現在我們關注的精神病學、長期護理和神經病學等領域。

Great, thank you.

太好了，謝謝。

Chris Shibutani, Goldman Sachs.

高盛的 Chris Shibutani。

Thank you. Maybe if I could move to the operating expense side of the equation, particularly with the guidance. Now thinking about how with INGREZZA, over the course of the several years, you did have periods where you reassessed, reinvested at a more extensive levels. How confident are you in terms of the current thinking about INGREZZA?

謝謝。也許如果我可以轉到等式的營運費用方面，特別是在指導方面。現在想想 INGREZZA 的發展情況，在過去的幾年裡，您確實有過重新評估、在更廣泛的層面上進行再投資的時期。您對目前關於 INGREZZA 的想法有多大信心？

And then reflecting upon what the potential will be in a market that obviously has some differences, how should we think about your confidence and potential need to adjust either up or down or in some other way with CRENESSITY's launch?

然後反思一下在一個明顯存在差異的市場中潛力有多大，我們應該如何看待您的信心和潛力需要隨著 CRENESSITY 的推出而進行向上、向下或以其他方式進行調整？

Yeah. I think it's very clear within this space that the number one driver of shareholder value is revenue growth, and that's exactly where we've been putting our money over the last five years in those periodic reassessments of INGREZZA that you referred to, whether it was sales force expansion or direct-to-consumer advertising and then more recently, another sales force expansion.

是的。我認為，在這個領域，股東價值的首要驅動力是收入成長，而這正是我們過去五年來在您對 INGREZZA 進行定期重新評估時所投入資金的地方，無論是銷售隊伍擴張還是直接面向消費者的廣告，以及最近的另一次銷售隊伍擴張。

So from an investment perspective, just over the last three years, you've seen us show tremendous SG&A leverage, going from the mid-50% of revenue in SG&A, all the way down to the low 40%. So the investment that you see this year in both CRENESSITY and the expanded sales force, it's going to be a little bit less leverage coming out of that.

因此從投資角度來看，僅在過去三年中，您就看到我們表現出巨大的銷售、一般和行政費用槓桿率，從銷售、一般和行政費用佔收入的 50% 左右一直下降到 40% 的低位。因此，您今年看到的對 CRENESSITY 和擴大銷售團隊的投資，其槓桿作用將會稍微減弱一些。

But the expectation is that when we look at '26 and beyond, we aren't sitting here today thinking that we're going to need a significant increase or change in infrastructure required to support both brands. CRENESSITY in and of itself being a rare disease and the nature of the patient population, we expect this to be extremely profitable, quite quickly. But that's something that will show up from a P&L leverage perspective as you think about 2026.

但我們的預期是，當我們展望26年及以後時，我們不會坐在這裡想著我們需要大幅增加或改變支持兩個品牌所需的基礎設施。CRENESSITY 本身就是一種罕見疾病，而且考慮到患者群體的性質，我們預計這很快就會帶來極高的利潤。但當你想到 2026 年時，從損益槓桿的角度來看，這一點就會顯現出來。

Marc Goodman, Leerink Partners.

馬克古德曼（Marc Goodman），Leerink Partners。

Yeah. Matt, with your comments on ordering patterns, are you suggesting that fourth quarter may have been helped by inventory? Did inventories change and you're expecting maybe first quarter for that to reverse?

是的。馬特，你對訂購模式的評論，是否意味著第四季度可能受到了庫存的幫助？庫存是否發生了變化？

And then I guess my question really is for Eiry to talk about the M1/M4, the 570 molecule that you're pushing forward. Can you just describe the characteristics of that product and how you expect it to be differentiated from the one that's on the market today?

然後我想我的問題是讓 Eiry 談談 M1/M4，即您正在推動的 570 分子。您能否描述一下該產品的特點以及您認為它與目前市場上的產品有何不同？

Yeah, I'll cover the ordering pattern question. Really is more of a Q1 phenomenon. The nature of our business, our wholesalers largely order on a Monday products delivered on Tuesday, and that's when revenue is recognized typically, and so when you just look at the calendar setup for the first quarter, you only have 12 Tuesdays. And then you have 14 Tuesdays that pop up in September.

是的，我將討論排序模式問題。確實更像是 Q1 現象。由於我們業務的性質，我們的批發商大多在周一訂購產品，週二交付，而這通常是確認收入的時間，因此，當您查看第一季的日曆設定時，只有 12 個星期二。然後你會在九月看到 14 個星期二。

So it nets itself out throughout the course of the year. We don't do anything to dictate the timing of orders. this may not become an issue, but I know it's something that I just flagged just in case there is noise around timing of orders because of the nature of just how the calendar falls. So nothing associated with Q4 that I would mention, Mark.

因此，它將在全年內實現淨收益。我們不會採取任何措施來規定訂單的時間。這可能不會成為問題，但我知道我只是想標記一下，以防由於日曆的性質而導致訂單時間出現混亂。所以，馬克，我沒有什麼好說的，與 Q4 有關。

And then Eiry would you like to answer the next one?

然後 Eiry 你想回答下一個問題嗎？

Yeah. Mark, thanks for the question. Happy to answer that. As we said in the prerecorded remarks, we are actually still completing the Phase 1 evaluation of the 570 M1/M4 molecule in that Phase 1 evaluation in healthy subjects. We have an opportunity to profile the pharmacology associated with both for both M4 pharmacology and M1.

是的。馬克，謝謝你的提問。很高興回答這個問題。正如我們在預先錄製的評論中所說，我們實際上仍在對健康受試者進行第 1 階段評估，完成 570 M1/M4 分子的第 1 階段評估。我們有機會對 M4 藥理學和 M1 相關的藥理學進行分析。

And whilst I can say that we were very confident and pleased with the results that we saw in schizophrenia in our Phase 2 study 4568 to the M4 selective agonist, there's obviously potential for a dual agonist to add additional potential benefit in areas such as cognition through the M1 effect.

雖然我可以說，我們對 M4 選擇性激動劑在第 2 階段研究 4568 中在精神分裂症方面取得的結果非常有信心和滿意，但雙重激動劑顯然有可能透過 M1 效應在認知等領域增加額外的潛在益處。

And so for that reason, we're very keen to take that molecule forward in the second half of this year to test it in a Phase 2 study of schizophrenia as well.

因此，我們非常希望在今年下半年推進這種分子的研究，並在精神分裂症的 II 期研究中進行測試。

Are there obvious differences versus Karuna's drug?

與 Karuna 的藥物相比有明顯的差異嗎？

Well, Karuna's drug is a pan muscarinic agonist. And so it not only hits M1 and M4, but also the other muscarinic subtype from M2, M3 and M5. And that's the reason why the peripheral trospium has to be added to the Coben molecule in order to manage the potential side effects associated with the off-target M2 M3 and M5 effect. So we do not hit M2 M3 or M5, and so we would anticipate there will be differences for a selective M1 M4.

嗯，卡魯納的藥物是一種泛毒蕈鹼激動劑。因此，它不僅會影響 M1 和 M4，還會影響 M2、M3 和 M5 中的其他毒蕈鹼亞型。這就是為什麼必須將週邊曲司氯銨添加到科本分子中，以控制與脫靶 M2 M3 和 M5 效應相關的潛在副作用的原因。因此，我們不會達到 M2 M3 或 M5，因此我們預期選擇性 M1 M4 會有差異。

And as I said, when we complete the Phase I and go into our Phase II study later this year, we'll be able to talk more about what we're anticipating and hoping to see.

正如我所說，當我們在今年稍後完成第一階段並進入第二階段的研究時，我們將能夠更多地談論我們期待和希望看到的內容。

Jeff Hung, Morgan Stanley.

摩根士丹利的 Jeff Hung。

Can you talk about the feedback that you heard from the end of Phase 2 meetings for Osavampator and 568? And for FCC, was there any concern by the agency on lack of dose response or the benefit was seen with the mainly with 20-milligram dose?

您能談談在 Osavampator 和 568 第二階段會議結束時聽到的回饋嗎？對於 FCC 來說，該機構是否擔心缺乏劑量反應，或者主要透過 20 毫克劑量就能看到益處？

Eiry, do you want to take that one?

Eiry，你想拿那個嗎？

Yes. We were very happy with the end of Phase 2 meeting for both Osavampator and for 568. And I think we got alignment and guidance from the agency for both of those interactions that was support of the registration program as we designed it and defined it, support of the dose selection particularly as you asked around 568.

是的。我們對 Osavampator 和 568 第二階段會議的結束感到非常高興。我認為，在這兩種互動中，我們都得到了該機構的協調和指導，即在我們設計和定義註冊計劃時提供支持，特別是對劑量選擇的支持，正如您在 568 中詢問的那樣。

Now there was complete support for moving forward with the 20-milligram dose into the Phase 3 program. We also got alignment on the endpoints that we were using and the nature of the whole registration plan. So our focus right now is on moving to implement those programs, we already initiated the Osavampator first Phase 3 acute study. And we are moving towards initiating the 568 study in the very near future as well.

現在，大家完全支持將 20 毫克劑量推進到第三階段計畫。我們也對所使用的端點和整個註冊計劃的性質進行了協調。因此，我們現在的重點是實施這些計劃，我們已經啟動了 Osavampator 第一階段 3 急性研究。我們也將很快啟動 568 項研究。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

This is Charlie Moore on for Brian. So we were just wondering, looking earlier in the pipeline about your Friedreich's ataxia gene therapy collaboration with Voyager. And it would just be great to get some color on how you think it could differentiate from current clinical stage gene therapies, one dual and one targeting cardiac tissue, as well as if that's still on track to initiate first in human trials this year.

這是查理摩爾 (Charlie Moore) 為布萊恩 (Brian) 主持的節目。所以我們只是想知道，您之前與 Voyager 公司在弗里德賴希共濟失調基因治療方面的合作情況如何。如果您能詳細了解它與目前臨床階段的基因療法（一種雙重療法和一種針對心臟組織的療法）的區別，以及它是否仍有望在今年首次啟動人體試驗，那就太好了。

Maybe I'll take this question, and I'll have Eiry fill any gaps on this. We're really excited about the FA program that we have with Voyager. It's something that we've been working on for several years as a part of our collaboration. We've gone through first and second-generation capsids that allow us to deliver free tax into targeted tissues.

也許我會回答這個問題，然後讓 Eiry 填補這方面的空白。我們對與 Voyager 合作的 FA 計劃感到非常興奮。這是我們多年來一直致力於合作的事情。我們已經經歷了第一代和第二代衣殼，它們使我們能夠將自由稅收運送到目標組織中。

And what we have in the approach here that's so exciting is that patients have the opportunity to have an IV-administered gene therapy that delivers free tax into the cardiovascular system as well as the CNS. So the cornerstone symptoms of the disease, either the movement component or heart disease, cardiovascular outcomes, would be addressed by our gene therapy in a stand-alone treatment.

我們採用的這種方法非常令人興奮，因為患者有機會接受靜脈注射基因治療，將自由基輸送到心血管系統和中樞神經系統。因此，我們可以透過獨立基因療法來治療疾病的基本症狀，無論是運動成分或心臟病、心血管結果。

So very excited about that. We are on track for graduating this program from preclinical to clinical development later this year.

我對此感到非常興奮。我們計劃在今年稍後將該項目從臨床前階段推進至臨床開發階段。

Mohit Bansal, Wells Fargo.

富國銀行的莫希特·班薩爾 (Mohit Bansal)。

Thank you for taking my question. Sorry for keeping -- staying on INGREZZA here. So if I look at the fourth quarter number, if I just straight line it, it looks like your low end of the guidance assumes just flat line using fourth quarter. So is there something massively changing in your contracting or the pricing dynamic? It does seem like that from your comments. So can you help us understand that?

感謝您回答我的問題。抱歉，我仍在這裡談論 INGREZZA。因此，如果我看第四季度的數字，如果我只是將其直線化，看起來您的指導低端假設只是使用第四季度的平線。那麼你們的合約或定價動態是否發生了重大變化？從您的評論來看，確實是這樣的。那麼你能幫助我們理解這一點嗎？

And then also, are you expecting or modeling any benefit of sales force expansion here? Because that would mean second quarter -- second half bump, but that doesn't seem to be part of the guidance here.

另外，您是否預期或模擬了銷售團隊擴張帶來的任何好處？因為這意味著第二季至下半年會出現成長，但這似乎不是此處指導的一部分。

Yeah. On the contracting front, just to be clear, we did enter into some contracts that have some incremental rebates, but it pretty much offsets the annual price increase. So from a year-over-year perspective on price, pretty flattish, a little sequential down maybe Q4 to Q1, as I mentioned earlier.

是的。在合約方面，需要明確的是，我們確實簽訂了一些有增量回扣的合同，但這幾乎抵消了年度價格上漲。因此，從同比價格來看，價格相當平穩，可能與第四季度相比第一季略有下降，正如我之前提到的。

So I understand that the straight-line math, there's a lot of variables at play including pace of new patient additions relative to discontinuations, for example, on a much bigger patient base. And so those are normal growing launch dynamics. And as we mentioned, with the sales force expansion, we do expect to have nice momentum in the second half of the year, but it's going to take a little bit of time for them to get up to full speed.

因此，我理解直線數學有很多變數在起作用，包括新患者增加的速度相對於停藥的速度，例如在更大的患者群中。這些都是正常成長的發射動力。正如我們所提到的，隨著銷售隊伍的擴大，我們確實預計今年下半年會有良好的發展勢頭，但他們需要一點時間才能達到全速。

Ash Verma, UBS.

瑞銀的 Ash Verma。

Thanks for taking my question. So just one more on INGREZZA. So do you expect to see more of the utilization management headwind in 2025 on the Medicare Part D plans? We've heard Part D plans are moving branded drugs lower, because they have the catastrophic coverage. And with that burden going up, they need to make up the dollars elsewhere. If you can comment on that, that would be great.

感謝您回答我的問題。關於 INGREZZA 再說一次。那麼，您是否預期 2025 年 Medicare Part D 計畫的利用管理將面臨更多阻力？我們聽說 D 部分計劃正在降低品牌藥物的價格，因為它們具有災難性保險。隨著負擔不斷增加，他們需要從其他地方彌補損失。如果您能對此發表評論，那就太好了。

Yeah. So just a quick comment. We don't expect to see any significant changes in terms of our coverage in 2025 versus 2024. And certainly, we're looking and monitoring closely what's happening with the first wave of medicines that have been negotiated and the impact potentially of other drugs in those classes. But so far, we're not seeing any major shifts.

是的。我只想簡短地評論一下。我們預計，2025 年與 2024 年相比，我們的覆蓋範圍不會有任何重大變化。當然，我們正在密切關注和監測已談判的首批藥品的進展情況，以及同類藥品可能產生的影響。但到目前為止，我們還沒有看到任何重大轉變。

And the other thing I'd point out is that because we are a designated small manufacturer, we get the phase-in benefit on the contribution to the catastrophic phase, so -- as does our competitors. So there's no one that's advantaged in that regard within the VMAT2 class.

我想指出的另一件事是，由於我們是指定的小型製造商，我們可以從災難階段的貢獻中獲得分階段收益，我們的競爭對手也是如此。因此，在 VMAT2 等級中，沒有人在這方面佔有優勢。

Sumant Kulkarni, Canaccord.

Sumant Kulkarni，Canaccord。

Good afternoon. Thank you for taking my question. It's another one on INGREZZA. The product has been on the market for some time now. Your comments suggest there's still some way to go on penetration in the tardive dyskinesia market. But we seem to be at a point every few quarters when the debate around the growth trajectory around INGREZZA seems to intensify. And then you kind of grow out of that by beating your initial numbers.

午安.感謝您回答我的問題。這是 INGREZZA 上的另一個。該產品已經上市一段時間了。您的評論表明，我們在遲發性運動障礙市場滲透方面還有一段路要走。但每隔幾個季度，我們似乎就會陷入這樣的境地：圍繞 INGREZZA 成長軌蹟的爭論似乎愈演愈烈。然後你就會透過超越最初的數字而擺脫這種困境。

So to help settle this uncertainty or debate somewhat what's your latest philosophy on offering any detail on what you think eventual peak sales potential for INGREZZA might be in the US?

那麼，為了幫助解決這種不確定性或進行某種程度的爭論，您最近的想法是什麼，能否提供一些細節，說明您認為 INGREZZA 在美國最終的最高銷售潛力是多少？

Yeah, it was funny. Kyle and I were talking about this earlier this week original models for INGREZZA were peak sales of $500 million. And here we are in 2024, having grown almost $500 million year-over-year with the market now being close to $4 billion.

是的，很有趣。本週早些時候，凱爾和我談到了這一點，INGREZZA 的原始模型的銷售額最高達到了 5 億美元。現在已經是 2024 年了，市場規模年增近 5 億美元，接近 40 億美元。

So we're not going to give a peak potential. But what we do see, as we -- as Eric has alluded to, that's still 9 out of 10 patients with part of dyskinesia are not currently being treated with the VMAT2 inhibitor.

所以我們不會給出峰值潛力。但我們確實看到，正如 Eric 所提到的那樣，仍有 90% 患有部分運動障礙的患者目前沒有接受 VMAT2 抑制劑治療。

So we do anticipate there's significant demand out there. And as you've said, there are ebbs and flows in the market development process for card up dyskinesia. Some are pretty clear to understand, others, less clear. But we do feel like there's a lot of growth trajectory ahead.

因此我們確實預期那裡會有很大的需求。正如您所說的，卡片式運動障礙的市場發展過程有起有落。有些相當容易理解，有些則不太清楚。但我們確實感覺到未來還有很大的成長空間。

Maybe just to add to that, part of our discussion that we had is the one of the really unique aspects of tardive dyskinesia is that we believe the underlying prevalence continues to grow at a rate that exceeds the growth rate of the general population.

也許只是想補充一點，我們討論的一部分是遲發性運動障礙的真正獨特方面之一是，我們認為潛在的患病率繼續以超過一般人群的增長率增長。

So getting your hands around market size and value is something that's dynamic. The antipsychotic prescription volume was about $75 million last year, and it continues to grow in the low digit number that's multiples above the growth rate of the general population.

因此，了解市場規模和價值是一件動態的事情。去年抗精神病藥物的處方金額約為 7500 萬美元，並且繼續以低位數增長，是總人口增長率的數倍。

So that's why you saw us increase our prevalence number late last year, and that's something that we'll continue to revisit on the annual basis. But we're ever more surprised as we get into the market and learn more about it is how large it can be. And how much work there is still ahead for us with that work, a lot more opportunity. And we're quite thankful to be in a situation where we have 30 more years of market easily to help build the market.

這就是為什麼你看到我們在去年年底增加了患病率，而且我們每年都會繼續重新審視這一點。但當我們進入市場並了解更多情況時，我們更加驚訝的是它的規模竟然如此之大。我們還有多少工作要做，還有更多的機會。我們非常慶幸自己能輕鬆擁有 30 多年的市場空間來幫助打造市場。

Myles Minter, William Blair.

邁爾斯·明特、威廉·布萊爾。

Maybe one for Eiry just back on 570. You haven't completed the Phase 1 yet, but just curious as to your decision to move in adults, experiencing schizophrenia, acute psychosis, and not Alzheimer's disease psychosis. Does that mean you're still contemplating that indication? Or is it maybe that you're seeing something on the tolerability side for that molecule that you want to go into adults first prior to the elderly population. Thanks very much.

也許是 570 上為 Eiry 準備的。您尚未完成第 1 階段，但我只是好奇您決定進入成年人行列，經歷精神分裂症、急性精神病，而不是阿茲海默症精神病。這是否意味著您仍在考慮該跡象？或者也許您看到了該分子耐受性方面的一些問題，因此想先將其用於成年人，然後再用於老年人群。非常感謝。

Yeah, happy to take that. I think obviously, we have experience with 568 for the M4 selective in the acute setting in adults, which makes it a pretty a straightforward choice to evaluate 570 in that patient population as well.

是的，很高興接受這個。我認為，顯然我們在成人急性環境中使用 568 進行 M4 選擇性治療方面擁有豐富的經驗，因此在該患者群體中評估 570 也是一個相當直接的選擇。

With respect to other potential indications, obviously, we remain very open to that. And as we continue to generate data, you may well see us going into different indications beyond that initial psychosis study.

對於其他潛在跡象，顯然我們對此保持開放態度。隨著我們不斷產生數據，您可能會看到我們在最初的精神病研究之外進入不同的適應症。

I think, Miles, too, this is Kyle. The interesting thing about the Mucinex to be discussed is that there's still a lot to learn about this as a target class. And fortunately, we have a number of molecules that allow us to compare and contrast the pharmacologies that we have.

我想，麥爾斯也一樣，這是凱爾。關於要討論的 Mucinex 的有趣之處在於，作為目標類別，仍有許多東西需要學習。幸運的是，我們有許多分子可以讓我們比較和對比我們擁有的藥理學。

One way to do that is look at a dual pharmacology in the same patient population and see what type of outcomes you can get from a selective and direct agonist that we have in 568. So there's a lot of value, a lot of opportunities here across the different molecules that we have and knowing that we can't do everything the same time. We like the approach that we have here with 568 going into bipolar mania and the dual going into schizophrenia.

其中一個方法是在同一患者群體中研究雙重藥理學，看看你能從 568 中的選擇性直接激動劑中獲得何種結果。因此，我們擁有的不同分子中存在著很大的價值，也有很多的機會，但我們知道，我們不能同時做所有的事情。我們喜歡這裡採用的方法，即 568 分為躁鬱症，而 568 分為精神分裂症。

Makes sense. Thanks.

有道理。謝謝。

Laura Chico, Wedbush Securities.

勞拉‧奇科（Laura Chico），韋德布希證券公司。

I'm sorry, just one clarification for me. With respect to the field force expansion, and I guess I'm trying to relate back to the 25% guidance here, wondering whether you're going to see the biggest benefit from driving new patient starts? Is this the channel expansion or increasing adherence. I guess I'm just trying to understand where the field force impact is most likely to be felt. Any commentary there?

抱歉，我只想澄清一件事。關於現場人員的擴張，我想我試圖與這裡的 25% 指導聯繫起來，想知道您是否會從推動新患者開始治療中看到最大的好處？這是通路擴張還是增加依從性。我想我只是想了解最有可能在哪裡感受到戰力的影響。有什麼評論嗎？

Yeah. A couple of things I'd point out with regards to the sales force expansion and our experience from prior expansions. First of all, I think we alluded to it earlier. When you hire essentially a new team or expand your existing team and you deploy them. It takes some time for them to come up to speed and to get their stride, so to speak. And so we do expect to see the majority of the impact from the expanded team as we go into the second half of the year.

是的。關於銷售隊伍擴張以及我們之前擴張的經驗，我想指出幾點。首先，我想我們之前提到過這一點。當您僱用一個新團隊或擴大現有團隊並部署他們。可以這麼說，他們需要一些時間來適應並取得進步。因此，我們確實預計，在進入今年下半年時，擴大團隊將產生最大的影響力。

Second thing is in terms of what's the benefit of the team, it's primarily in driving new patient starts. They do a lot of education. They're able to increase our reach and also increase our presence in existing practices, driving recognition and diagnosis, and of course, initiation with INGREZZA.

第二件事是關於團隊的益處，它主要在推動新患者的開始。他們做了很多教育工作。他們能夠擴大我們的影響力，也能增強我們在現有實踐中的存在感，推動認知和診斷，當然還有 INGREZZA 的啟動。

The two areas that we expanded our team into were psychiatry and long-term care. And as Kyle mentioned earlier, psychiatry continues to be the segment that has the largest patient potential and is still fast-growing. And we recognize that we hadn't really increased our footprint in psychiatry since going back to, I think it was 2018.

我們將團隊擴展至精神病學和長期照護兩個領域。正如凱爾之前提到的，精神病學仍然是擁有最大患者潛力且仍在快速成長的領域。我們認識到，自 2018 年以來，我們在精神病學領域的影響力並沒有真正擴大。

So ultimately, we do see the opportunity to expand our footprint in both psychiatry and LTC those teams are relatively brand new. And we do expect to see the benefit of having that expanded presence, especially in the second half of the year. Thank you.

因此，最終，我們確實看到了擴大我們在精神病學和 LTC 領域影響力的機會，這些團隊相對較新。我們確實希望看到擴大業務帶來的好處，尤其是今年下半年。謝謝。

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Hi, good evening. Thanks for keeping me in. I have two very quick questions. Firstly, just follow-up on all the questions around the INGREZZA guidance. It certainly seems quite conservative given all the other comments around the trends. But it sounds like you're taking a conservative view, keeping in mind kind of the increased hurdles with regards to prior auth if you can comment if that's kind of what's driving this conservatism or if you're missing something there?

嗨，晚上好。謝謝你留我。我有兩個非常簡單的問題。首先，只需跟進有關 INGREZZA 指南的所有問題。考慮到圍繞該趨勢的所有其他評論，它確實顯得相當保守。但聽起來您是持保守觀點的，考慮到事先授權方面的障礙越來越大，您是否可以評論一下這是否是推動這種保守主義的原因，或者您是否忽略了什麼？

And then just with regards to the 11 patient forms for CRENESSITY, can you give us some color around where these patients are being treated and something about kind of what was the trigger for prescribing the drug to these patients? Were they sort of very high corticosteroids or were they sort of not well controlled on their current treatments? Any color would be helpful.

那麼，關於 CRENESSITY 的 11 份病患表格，您能否告訴我們這些病患接受治療的情況，以及為這些病患開藥的動機是什麼？他們的皮質類固醇劑量是否過高，或者他們目前的治療控制得是否不好？任何顏色都會有幫助。

Yes. On the INGREZZA piece, we've commented previously. I think that there are a number of variables that play out here towards the end of 2024 that reads on our thoughts on 2025. Competitive pressures there with our competitor in this space with their XR formulation, getting to a once-a-day type of medicine after a complex titration regimen. We've also seen the competitive pressures there on the payer front.

是的。關於 INGREZZA 的作品，我們之前已經做出評論。我認為，到 2024 年底，會出現許多變量，這些變量將影響我們對 2025 年的想法。我們在這個領域面臨競爭壓力，我們的競爭對手採用 XR 配方，經過複雜的滴定方案後獲得每日一次的用藥。我們也看到了付款方方面的競爭壓力。

But I don't want to discount also something that we talked about the disruption of our own sales force expansion in Q4. These are things that we saw play out over the course of the second half of next year -- or last year, excuse me. And we think that will still be a factor here for us as we start 2025. But I don't want to dwell too much on the headwinds that we have here.

但我也不想忽視我們談到的第四季我們自己的銷售團隊擴張受到干擾的問題。這些都是我們在明年下半年——或者對不起，是去年——看到的事情。我們認為，在 2025 年伊始，這仍將是我們的一個考慮因素。但我不想多談論我們目前面臨的阻力。

Also, I want to call out all the things that we think will benefit us here into 2025 in subsequent years. And I've touched on these already, but really, that sales force expansion that caused that disruption in Q4 will start playing dividends this year and certainly able to lean on that heavily in subsequent years as well.

此外，我想指出我們認為在 2025 年之後幾年將對我們有利的所有事項。我已經談到這些了，但實際上，導致第四季度混亂的銷售隊伍擴張將在今年開始發揮紅利，並且肯定能夠在接下來的幾年里大大依賴這一點。

And then our differentiated product across things like efficacy, dosing regimen, other formulations for patients with difficulties. These are all things that will play out with this upside sales force and allow us to do quite nicely over time. So we balance both of these things in terms of our guidance.

然後，我們的產品在功效、給藥方案、針對有困難的患者的其他配方等方面具有差異化。這些都是將透過這支上行銷售隊伍發揮作用並讓我們隨著時間的推移取得良好業績的事情。因此，我們在指導方面平衡了這兩點。

We are seeing growth this year. It's not going to be as the guidance suggests, as large as it was in 2024, which was our largest growth year ever, but we still see significant growth here in this year and certainly in the following future years as well.

我們今年看到了成長。它不會像指導意見所建議的那樣，像 2024 年（我們有史以來最大的增長年）那樣龐大，但我們仍然看到今年以及未來幾年都將出現顯著的增長。

Yeah. Let me just quickly comment on the sort of what we're seeing in terms of the treatment forms coming in and sort of the diversity of the patients. So obviously, we've done work leading up to the launch. Our expectation is that adoption will be probably earlier or faster in the pediatric segment. We expect that we'll also see more rapid adoption in the centers of excellence.

是的。讓我快速評論一下我們所看到的治療形式和患者的多樣性。顯然，我們在發布之前已經做了大量工作。我們預期，兒科領域的採用可能會更早或更快。我們預計，我們還將看到卓越中心更快採用該技術。

However, early on with a relatively small sample size, so to speak, what we are seeing is treatment forms are coming in from community endocrinologists, from endocrinologists that are part of TG hospitals or CH clinics. We're seeing patients getting started that are pediatric patients. We're seeing adult patients, getting started.

然而，早期樣本量相對較小，我們看到的治療表格來自社區內分泌學家、TG 醫院或 CH 診所的內分泌學家。我們看到剛開始治療的患者是兒科患者。我們正在接診成年患者，一切才剛開始。

So really, it's very diverse and across the board. And as I said before, just really excited about the momentum and the trajectory that we're on here. It's early days yet. And as Matt said, there's still a lot of people that we need to reach and a lot of work that we need to do.

所以實際上，它非常多樣化且全面。正如我之前所說，我對我們所處的勢頭和軌跡感到非常興奮。現在還為時過早。正如馬特所說，我們還需要接觸很多人，還有很多工作要做。

But I think that the fact that we had invested in [CSAT] education that we had teams in the field in the second half of last year, and we were well prepared for an early approval has really set us up for success this year and beyond with CRENESSITY.

但我認為，事實上我們已經對 [CSAT] 教育進行了投資，去年下半年我們在該領域組建了團隊，並且為提前批准做好了充分準備，這些都為我們今年及以後 CRENESSITY 的成功奠定了基礎。

Thank you.

謝謝。

Uy Ear, Mizuho.

黃耳、瑞穗。

Hey, guys. Thanks for taking in question. So on questions on INGREZZA, quick one on 4Q. Was there significant or any volume growth in the quarter from Q3 to Q4?

嘿，大家好。感謝您的提問。關於 INGREZZA 的問題，首先要快速問一個關於 4Q 的問題。從第三季到第四季，銷量是否有顯著的成長？

And quickly on the guidance as well. Does the guidance assume benefits from the sales force expansion? Just wanted to make sure we're clear on that.

並快速提供指導。該指引是否假設銷售隊伍擴張會帶來收益？只是想確保我們清楚這一點。

And thirdly, if I can, could you maybe just help us think how to perhaps think about the INGREZZA sales post 2027, I guess, after the price negotiation for state?

第三，如果可以的話，您能否幫助我們思考一下，在國家價格談判之後，如何考慮 2027 年以後 INGREZZA 的銷售情況？

Yeah, I think the answer to your questions are, yes, we have included the sales force expansion in our guidance range. Obviously, at the high end of the range, it's contributing at a quicker pace. And so I would just say that the answer to your first two questions are yes.

是的，我認為您的問題的答案是，是的，我們已將銷售團隊擴張納入我們的指導範圍。顯然，在範圍的高端，它的貢獻速度更快。所以我只想說，你的前兩個問題的答案是肯定的。

In regards to what happens post 2027, that's something, as Eric mentioned, we're keeping our eyes out looking to see what is happening in the space with other similarly situated product categories. But at the end of the day, for us, our main focus right now is growing the TD market, growing the presence of INGREZZA.

至於 2027 年之後會發生什麼，正如 Eric 所提到的，我們正在密切關注該領域以及其他類似產品類別的發展。但歸根結底，對我們來說，我們目前的主要關注點是擴大 TD 市場，擴大 INGREZZA 的影響力。

There's going to be a whole lot of uncertainty, I'm sure, through the whole IRA implementation, hard to predict. But what we can control is ensuring that patients with TD get diagnosed and get opportunity to take INGREZZA.

我確信，在整個愛爾蘭共和軍實施過程中，將會存在許多不確定性，很難預測。但我們可以控制的是確保 TD 患者得到診斷並有機會服用 INGREZZA。

Brian Abrams, RBC Capital Markets.

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

Hi. This is Joe on for Brian. So related to the earlier question on TD market share split, I believe the market share has been pretty stable over time even after competitor [XR] launch.

你好。這是喬，取代布萊恩。因此，對於先前關於 TD 市佔率分配的問題，我認為即使在競爭對手 [XR] 推出後，市佔率仍然相當穩定。

I was just wondering if there's anything more that will drive the changes to the competitive dynamics this year and how are you thinking about the changes in payer dynamics beyond 2025? Do you believe the complexity and the dynamics will persist?

我只是想知道今年是否還有更多因素推動競爭態勢的變化，以及您如何看待 2025 年後付款人態勢的變化？您是否相信這種複雜性和動態性將會持續存在？

Yeah. So we've always said that we have a formidable competitor. And they appear to have gained a few share points in 2024 due to the rollout of their extended release formulation of deter modified tetrabenazine, as one might expect.

是的。所以我們一直說我們有一個強大的競爭對手。而且正如人們所預料的那樣，由於推出了緩釋型四苯嗪配方，他們的市佔率似乎在 2024 年上漲了一些。

But INGREZZA is the leader in the VMAT2 category, and we continue to project growth for the class. And for INGREZZA, there is, as I mentioned earlier, a lot of headroom with 9 out of 10 patients with TD as yet undiagnosed and untreated currently with VMAT2 inhibitors. So we certainly are bullish in terms of the long-term and near-term potential of INGREZZA to continue driving that growth.

但 INGREZZA 是 VMAT2 類別的領導者，我們預計該類別將繼續成長。對於 INGREZZA 而言，正如我之前提到的，它有很大的發展空間，因為目前 10 個 TD 患者中有 9 個尚未診斷，也未使用 VMAT2 抑制劑進行治療。因此，我們當然看好 INGREZZA 的長期和近期潛力，並繼續推動這一成長。

And with our more exclusivity I'm glad that we have that time to do it. Thinking beyond 2026 and 2027, I mentioned that it's a complex payer environment. and the Inflation Reduction Act makes it even more complex. But we're going to continue to do what we need to do to make sure that patients have access to INGREZZA this year and in coming years.

由於我們擁有更多的獨家權利，我很高興我們有時間做這件事。考慮到 2026 年和 2027 年以後的情況，我提到這是一個複雜的付款人環境。而《通貨膨脹削減法案》則使情況變得更加複雜。但我們將繼續做我們需要做的事情，以確保患者今年和未來幾年能夠獲得 INGREZZA。

And maybe just to add to that as a reminder to everyone, I think we have it in our remarks, but we do have been given these specified small manufacturer exemption as well as a small biotech exemption. So that's confirmed. And we would expect our price negotiation observation event to be in 2029.

也許只是為了提醒大家，我想我們的評論中已經提到了這一點，但我們確實獲得了這些指定的小型製造商豁免以及小型生物技術豁免。所以這已得到確認。我們預計我們的價格談判觀察活動將在 2029 年舉行。

So to Eric's point, we have the opportunity to learn, prepare and adjust to the new world that we'll all be in over the next couple of years as products are negotiated at CMS and seeing how that affects potential other products in similar categories.

所以正如 Eric 所說，我們有機會學習、準備和適應未來幾年我們將要身處的新世界，因為產品將在 CMS 進行談判，並觀察這將如何影響類似類別的其他潛在產品。

Evan Seigerman, BMO Capital Markets.

埃文·塞格曼 (Evan Seigerman)，BMO 資本市場。

Malcolm Hoffman for Adam Seigerman. I wanted to ask if you could talk about the decision to amend the agreement with Takeda in get worldwide development and commercial rights ex-Japan for Osavampator? Is this decision driven by increased confidence in pursuing additional indications beyond MDD? Or was this decision more based on just the profile in MDD alone?

Malcolm Hoffman for Adam Seigerman.我想問您是否可以談談修改與武田的協議以獲得 Osavampator 在日本以外的全球開發和商業權利的決定？這項決定是否是因為對追求 MDD 以外的更多適應症的信心增強而推動的？或者這個決定僅僅基於 MDD 中的概況？

I'll start. This is Kyle. I think that we're very excited about the data that we have that came out of the Phase II program and quite frankly, so is Takeda. As we've seen from Decade over the past several years, they been making a number of strategic decisions that move them away from kind of classical psychiatric disease and MDD Osavampator fits squarely in there.

我先開始。這是凱爾。我認為我們對第二階段計劃得出的數據感到非常興奮，坦白說，武田也是如此。正如我們在過去幾年中看到的，Decade 做出了一系列策略決策，使其遠離典型的精神疾病，而 MDD Osavampator 正好符合這項要求。

And the nature of our collaboration really affected their P&L in terms of their expense profile on a year-to-year basis. So knowing that they appreciated the data that we have and still like to be involved in this. we both work towards an arrangement where they are able to continue developing this asset in their territory, which is Japan.

我們合作的性質確實影響了他們的損益表，即逐年的費用狀況。所以知道他們很欣賞我們擁有的數據並且仍然喜歡參與其中。我們雙方共同努力，達成協議，使他們能夠在自己的領土，也就是日本，繼續開發這項資產。

This particular compound came out of efforts from their Japanese R&D facility. And there's quite a bit of pride there and able to take this forward in their country, and we'll continue to work together to develop list of Osavampator outside of Japan, both tepotinhare of the economics.

這種特殊的化合物是其日本研發機構努力的成果。他們為能夠在自己的國家推動這項進程感到十分自豪，我們將繼續共同努力，在日本以外開發更多 Osavampator，無論是經濟還是社會。

So it's a win-win for both companies. We're able to move forward more quickly being a smaller and nimble company. And we think that, that will ultimately allow us to have the best opportunity to bring this medicine to patients as quickly as we possibly can. So we're excited. We continue to work with our team there, and we'll look to put this into Phase 3 this year.

因此，這對兩家公司來說是雙贏的。作為一家規模較小但靈活的公司，我們能夠更快地前進。我們認為，這最終將使我們有最好的機會盡快將這種藥物帶給患者。所以我們很興奮。我們將繼續與那裡的團隊合作，並期待今年將其納入第三階段。

And it does appear that there are no further questions at this time. I would now like to turn it back to Kyle for any additional or closing remarks.

目前似乎沒有其他問題。現在我想請凱爾發表補充意見或結語。

Thank you, and thanks, everyone, for joining the call this afternoon. As you can see we've got a lot going on here at the company. And we've hit on a number of different points throughout our conversation through our opening remarks about 2025 being a year of execution and a year of evolution.

謝謝大家，也謝謝大家參加今天下午的電話會議。正如您所看到的，我們公司有很多事情要做。在整個談話過程中，我們在開場白中提到了許多不同的觀點，即 2025 年是執行之年和發展之年。

And it really is -- and it does start with our efforts on our commercial products, INGREZZA and CRENESSITY the goal here is to drive revenue growth and diversification over time. So it's very important we continue to execute on our commercial medicines and make sure that they are brought to patients as quickly and broadly as possible.

事實確實如此 - 它始於我們對商業產品 INGREZZA 和 CRENESSITY 的努力，這裡的目標是隨著時間的推移推動收入成長和多樣化。因此，繼續執行我們的商業藥物並確保它們盡快、盡可能廣泛地提供給患者非常重要。

The other pieces of the execution involves supporting those programs that are in process in our pipeline. We've talked about our Phase 3 assets, those of Osavampator in NBI-568 in MDD and schizophrenia, successful respectively. And that's just the tip of the iceberg. We have programs in Phase 2 coming onboard from our muscarinic portfolio, we have data readouts that span Phase 2 and Phase 3 MDD and the adjunctive treatment of schizophrenia as well as the dyskinesia associated with serial policy a couple of Phase 1 starts this quarter.

執行的其他部分涉及支援我們正在進行的流程中的程序。我們已經討論了我們的第三階段資產，即 Osavampator 在 NBI-568 中分別在 MDD 和精神分裂症方面的成功。這只是冰山一角。我們的毒蕈鹼藥物組合中有處於第 2 階段的項目，我們擁有涵蓋第 2 階段和第 3 階段 MDD 的數據讀數以及精神分裂症的輔助治療以及與序列政策相關的運動障礙，其中第 1 階段的幾個項目於本季度啟動。

And then the fun begins the real concept of diversified and sustainable portfolio with our R&D transformation in bringing new products that are in the space of peptides, antibodies and gene therapy. Those are all things that become a reality in the second half of this year. So we're extremely excited about sharing this news with you as we move forward into 2025 and and meeting you all at the healthcare conferences throughout the course of the year.

然後，隨著我們的研發轉型，多元化和永續投資組合的真正概念開始發揮作用，帶來勝肽、抗體和基因治療領域的新產品。這些都將在今年下半年成為現實。因此，我們非常高興在 2025 年之際與您分享這一消息，並在全年的醫療保健會議上與大家見面。

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

今天的節目到此結束。感謝您的參與。您可以隨時斷開連接，並享受美好的下午。再見。