Neurocrine Biosciences Inc (NBIX) 2025 Q4 法說會逐字稿

Hello, and welcome, everyone, joining today's Neurocrine Biosciences fourth quarter and fiscal year 2025 earnings call. (Operator Instructions) Please note, this call is being recorded. (Operator Instructions)

大家好，歡迎參加今天的Neurocrine Biosciences第四季及2025財政年度業績電話會議。（操作員指示）請注意，本次通話正在錄音。（操作說明）

And it is now my pleasure to turn the meeting over to Todd Tushla, Vice President of Investor Relations. Please go ahead.

現在我很高興將會議交給投資者關係副總裁托德·圖什拉。請繼續。

Happy Wednesday to everyone, and welcome to Neurocrine Biosciences fourth quarter and 2025 year-end earnings call. With me today are Kyle Gano, Chief Executive Officer; Matt Abernethy, Chief Financial Officer; Eric Benevich, Chief Commercial Officer; Sanjay Keswani, Chief Medical Officer; and for the first time, we are very pleased to be joined by Samir Siddhanti, Vice President of Strategy and Corporate Development.

祝大家週三快樂，歡迎參加Neurocrine Biosciences第四季及2025年終財報電話會議。今天與我一同出席的有：執行長 Kyle Gano；財務長 Matt Abernethy；首席商務官 Eric Benevich；首席醫療官 Sanjay Keswani；以及我們非常高興首次邀請到策略與企業發展副總裁 Samir Siddhanti 加入我們。

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. After prepared remarks, we'll be happy to address any questions.

在今天的電話會議中，我們將發表一些前瞻性聲明。這些聲明存在一定的風險和不確定性，我們的實際結果可能與此有重大差異。我建議您仔細閱讀我們最新提交給美國證券交易委員會的文件中討論的風險因素。在發言結束後，我們將樂意回答大家的問題。

With that, Kyle, take it away.

那麼，凱爾，開始吧。

Thanks, Todd. Good afternoon, everyone. A hallmark of a healthy company is the strength of the foundation beneath it. As Neurocrine enters 2026, our foundation is stronger than at any point in our more than 30-year history and it continues to strengthen, with growing enterprise-wide momentum and strategic and balanced diversification, Neurocrine has entered a new era of meaningful growth led by our first and best-in-class commercial brands. INGREZZA performance continues to impress, strategic investments in access and sales force expansion drove a record year for both new and total prescriptions.

謝謝你，托德。大家下午好。一個健康公司的標誌是其堅實的基礎。隨著 Neurocrine 進入 2026 年，我們的基礎比我們 30 多年曆史上的任何時候都更加穩固，並且還在不斷加強。隨著企業整體發展勢頭的增強以及戰略性和平衡性多元化，Neurocrine 已經進入了一個由我們一流的商業品牌引領的、意義深遠的增長的新時代。INGREZZA 的表現持續令人印象深刻，在市場准入和銷售團隊擴張方面的策略性投資推動了新處方和處方總量的創紀錄一年。

This momentum carries us into 2026, where despite nine years post launch, we expect double-digit volume-driven growth supported by continued demand from the roughly 9 out of 10 TD or HD chorea patients not currently taking a VMAT2 inhibitor.

這一勢頭將我們帶入 2026 年，儘管上市已有九年，但我們預計銷量將實現兩位數增長，這得益於目前約有 90% 的 TD 或 HD 舞蹈症患者尚未服用 VMAT2 抑製劑，而這些患者的需求將持續增長。

Like INGREZZA, CRENESSITY's launch has also been exceptionally strong. By the end of the fourth quarter, our first full commercial year after its approval in December 2024, prescriptions covered over 10% of the classic and general adrenal hyperplasia patient population, underscoring the tremendous unmet need. What a great start, and I'd like to thank our team for making this all possible.

與 INGREZZA 一樣，CRENESSITY 的上市也異常強勁。到第四季末，也就是自 2024 年 12 月獲得批准後的第一個完整商業年度，處方涵蓋了超過 10% 的經典型和一般型腎上腺增生症患者群體，凸顯了巨大的未滿足需求。多麼棒的開端！我要感謝我們的團隊，是他們讓這一切成為可能。

This strong early adoption across patients, caregivers and prescribers reinforces our conviction that CRENESSITY will become Neurocrine's second blockbuster product. With an FDA-approved label supporting uncompromised efficacy, including an efficacious first dose with no requirement for titration, multiple formulations for pediatric and adult populations and a favorable safety and tolerability profile, CRENESSITY is rapidly becoming the standard of care for patients with classic CAH. This profile mirrors the attributes that supported the success of INGREZZA and underscores our confidence in CRENESSITY's impact for patients and Neurocrine moving forward.

患者、照護人員和處方醫生對 CRENESSITY 的早期強烈接受，更加堅定了我們對 CRENESSITY 將成為 Neurocrine 第二個重磅產品的信念。CRENESSITY 獲得了 FDA 批准的標籤，支持其療效不受影響，包括無需滴定即可有效服用的首劑，針對兒童和成人人群的多種配方，以及良好的安全性和耐受性，因此正在迅速成為經典 CAH 患者的標準治療方案。此特性與 INGREZZA 的成功特性相呼應，並強調了我們對 CRENESSITY 未來對患者和 Neurocrine 的影響的信心。

Turning to research and development. At our December R&D Day, we outlined three strategic pillars. First, we aim to lead the VMAT2 category by leveraging our deep INGREZZA experience and advancing next-generation VMAT2 inhibitors. By way of background, INGREZZA was the first approved treatment for tardive dyskinesia and Neurocrine paved the path for the development of new medicines in this space. Our nearly 20-year history provides a durable foundation for category leadership.

轉向研發。在12月的研發日上，我們概述了三大戰略支柱。首先，我們的目標是利用我們在 INGREZZA 領域的深厚經驗，推進下一代 VMAT2 抑制劑的研發，從而引領 VMAT2 類別。作為背景介紹，INGREZZA 是第一個獲準用於治療遲發性運動障礙的藥物，而 Neurocrine 為該領域新藥的研發鋪平了道路。我們近 20 年的歷史為我們在品類中的領先地位奠定了堅實的基礎。

This starts with NBI-'890, which recently entered into Phase 2 in tardive dyskinesia and with NBI-'675, which is falling close behind. Both of these products have the potential for long-acting injectable formulations. Second, we are delivering on the promise of CRF through a two-pronged approach: advancing next-generation CRF1 antagonist, such as NBIP-'1435 in CAH and expanding the platform with CRF2 agonist starting with NBIP-'2118 into adjacent areas, including metabolic diseases such as obesity.

首先是 NBI-'890，它最近進入了遲發性運動障礙的 2 期臨床試驗；其次是 NBI-'675，它緊隨其後。這兩種產品都有可能製成長效注射劑型。其次，我們正在透過雙管齊下的方法來兌現 CRF 的承諾：推進下一代 CRF1 拮抗劑（如 CAH 中的 NBIP-'1435）的研發，並將 CRF2 激動劑（從 NBIP-'2118 開始）的平台擴展到鄰近領域，包括肥胖等代謝性疾病。

For more than 30 years, Neurocrine has been a pioneer in CRF biology, and this experience uniquely positions us to evolve and expand what CRF-based therapies can deliver. Third, we are maximizing and evolving the pipeline, which is stronger than ever. This is led by our late-stage industry-leading neuropsychiatry portfolio, including two Phase 3 programs, osavampator, major depressive disorder and direclidine in schizophrenia.

30多年來，Neurocrine一直是CRF生物學領域的先驅，這項經驗使我們能夠以獨特的方式發展和擴展基於CRF的療法所能提供的功能。第三，我們正在最大限度地利用和改進人才儲備，使其比以往任何時候都更加強大。這主要得益於我們處於後期階段的領先業界的神經精神病學產品組合，其中包括兩個 3 期項目：osavampator（用於治療重度憂鬱症）和 direclidine（用於治療精神分裂症）。

Like INGREZZA and CRENESSITY before them, both represent potential first and best-in-class medicines. We expect top-line data from the osavampator studies in the first of two direclidine studies in 2027 which is shaping up to be the most data-rich year in Neurocrine's history.

與之前的 INGREZZA 和 CRENESSITY 一樣，它們都代表著有可能成為同類首創和同類最佳藥物。我們預計 2027 年將公佈 osavampator 研究的初步數據，這是兩項 direclidine 研究中的第一項，而 2027 年預計將成為 Neurocrine 歷史上數據最豐富的一年。

In 2025, we achieved our Phase 1 through Phase 3 objectives for the first time, making it the most productive clinical year in our history. We also have a clear line of sight to repeating this level of performance in 2026, accelerating us towards our goal of delivering one new medicine every two years at steady state.

2025 年，我們首次達成了第 1 期至第 3 期目標，成為我們史上成果最豐碩的臨床年份。我們有明確的目標，在 2026 年再次達到這樣的業績水平，這將加速我們實現每兩年穩定推出一種新藥的目標。

As I said from the outset, we entered 2026 with the strongest foundation in Neurocrine's history. It is incumbent upon me, our leadership team and the entire organization to continue executing and delivering for patients and shareholders. We appreciate your support.

正如我一開始所說，我們以Neurocrine歷史上最堅實的基礎進入了2026年。我、我們的領導團隊以及整個組織有責任繼續為病人和股東執行和交付成果。感謝您的支持。

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

接下來，我將把電話交給馬特。

Thank you, Kyle, and good afternoon, everyone. 2025 was a noteworthy year for Neurocrine as total product sales grew to more than $2.8 billion, representing 22% year-over-year growth. This performance reflects continued strength and durability from INGREZZA and the successful initial launch of CRENESSITY. Together, these products form the foundation of our growth and generate durable cash flows that support long-term shareholder value creation.

謝謝凱爾，大家下午好。 2025年對Neurocrine來說是值得紀念的一年，產品總銷售額成長至超過28億美元，較去年同期成長22%。這一表現體現了 INGREZZA 的持續實力和持久性，以及 CRENESSITY 的成功上市。這些產品共同構成了我們成長的基礎，並產生了持久的現金流，從而支持了股東價值的長期創造。

INGREZZA generated just over $2.5 billion in revenue, up 9% year-over-year, driven by double-digit volume growth, partially offset by pricing concessions associated with formulary access investments to support long-term growth. Fourth quarter performance was in line with expectations outlined on our Q3 call. New prescriptions remain near record levels achieved in Q3, a strong result given the ongoing sales force expansion.

INGREZZA 創造了略高於 25 億美元的收入，年增 9%，這主要得益於兩位數的銷售成長，但部分被與支持長期成長的處方集准入投資相關的定價讓步所抵消。第四季業績符合我們在第三季財報電話會議上提出的預期。新處方數量仍接近第三季創下的歷史最高水平，考慮到銷售隊伍的持續擴張，這是一個強勁的成績。

Looking ahead, we are guiding to INGREZZA sales in the range of $2.7 billion to $2.8 billion in 2026, representing approximately 10% growth. This outlook reflects continued double-digit volume growth, including contributions from the expanded sales force in the second half of the year partially offset by price declines tied to formulary access improvements implemented in 2025. Overall, we expect net pricing in 2026 to be relatively consistent with levels exiting 2025. INGREZZA enters the year with strong NRx momentum, broad access and an expanded commercial team ready to execute.

展望未來，我們預計 INGREZZA 2026 年的銷售額將在 27 億美元至 28 億美元之間，成長約 10%。這項展望反映了兩位數的銷售持續成長，其中包括下半年擴大的銷售團隊所做出的貢獻，但部分被 2025 年實施的處方集准入改進措施所帶來的價格下降所抵消。整體而言，我們預計 2026 年的淨價格將與 2025 年底的水準保持相對一致。INGREZZA 帶著強勁的 NRx 勢頭、廣泛的市場准入以及一支準備就緒、規模擴大的商業團隊進入新的一年。

For CRENESSITY, we exited 2025 with over $300 million in net product sales and approximately 10% of addressable patients being prescribed CRENESSITY. As a first-in-disease launch, quarter-to-quarter enrollment form activity can be variable, but what gives us confidence is the number of patients on therapy, refill behavior and the speed of reimbursement.

對於 CRENESSITY，到 2025 年底，我們的淨產品銷售額超過 3 億美元，大約 10% 的目標患者正在服用 CRENESSITY。作為首個針對該疾病的上市產品，季度註冊表格的活躍度可能會有所波動，但讓我們充滿信心的是接受治療的患者人數、續藥行為和報銷速度。

Feedback remains extremely positive and our first year on the market exceeded both internal and external expectations. Given that CRENESSITY is the first product approved for classic CAH in more than 70 years, with much still to learn around market dynamics, we are not providing specific sales guidance for 2026. Later in the call, Eric will discuss the initiatives underway to continue developing this attractive market.

回饋仍然非常積極，我們上市第一年的業績超出了內部和外部的預期。鑑於 CRENESSITY 是 70 多年來首個獲準用於治療經典 CAH 的產品，並且對市場動態還有很多需要了解的地方，因此我們不提供 2026 年的具體銷售指導。在稍後的通話中，埃里克將討論為繼續開發這個有吸引力的市場而正在採取的各項舉措。

Turning to the financials. Our cash position increased by approximately $700 million from $1.8 billion at the end of 2024 to $2.5 billion at the end of 2025, reflecting strong operating performance and a healthy balance sheet. While maximizing near-term profitability is not our primary objective, we remain highly profitable, delivering approximately 30% non-GAAP operating margin or roughly $850 million of non-GAAP operating income for 2025, including $83 million of R&D milestones and IP R&D expense.

接下來來看財務數據。我們的現金儲備從 2024 年底的 18 億美元增加到 2025 年底的 25 億美元，增加了約 7 億美元，這反映了強勁的經營業績和健康的資產負債表。雖然最大化近期獲利能力並非我們的主要目標，但我們仍保持著很高的獲利能力，預計到 2025 年，非 GAAP 營業利潤率將達到約 30%，非 GAAP 營業收入將達到約 8.5 億美元，其中包括 8,300 萬美元的研發里程碑和知識產權研發費用。

In 2026, we expect another strong year of non-GAAP operating income, driven by increased product sales partially offset by investments across SG&A and R&D. These investments align with our top capital allocation priorities of driving revenue growth and advancing our pipeline. SG&A growth year-over-year primarily reflects investments related to our 2026 sales force expansion, which we expect to be completed by the end of the first quarter. At the midpoint of our guidance range, GAAP SG&A is expected to be in the low 40% of sales for 2026.

2026 年，我們預計非 GAAP 營業收入將再次強勁成長，這主要得益於產品銷售的成長，但部分被銷售、管理及行政費用和研發方面的投資所抵銷。這些投資符合我們推動營收成長和推動產品線建設的首要資本配置目標。銷售、一般及行政費用年增率主要反映了與我們 2026 年銷售隊伍擴張相關的投資，我們預計該擴張將在第一季末完成。根據我們的指導範圍中位數，2026 年 GAAP SG&A 預計將佔銷售額的 40% 左右。

R&D expense growth reflects a full year of investment in our Phase 3 programs for osavampator and direclidine with data expected in 2027 as well as the initiation of multiple Phase 2 and Phase 1 programs, including obesity. Overall, we expect GAAP R&D expense, excluding approximately $25 million in milestones to be in the mid-30% of sales range, consistent with our prior commentary.

研發費用成長反映了我們對 osavampator 和 direclidine 的 3 期項目進行了一整年的投資，預計將於 2027 年獲得數據，以及啟動了多個 2 期和 1 期項目，包括肥胖症項目。總體而言，我們預計 GAAP 研發費用（不包括約 2,500 萬美元的里程碑付款）將佔銷售額的 30% 左右，這與我們先前的評論一致。

Overall, 2026 is shaping up to be another important year for Neurocrine as we continue to grow INGREZZA and CRENESSITY while advancing our pipeline. We entered the year with strong momentum and are well positioned for continued growth.

總體而言，2026 年對 Neurocrine 來說將是另一個重要的年份，我們將繼續發展 INGREZZA 和 CRENESSITY，同時推進我們的研發管線。今年年初我們勢頭強勁，並已做好持續成長的準備。

With that, I'll turn the call over to Eric Benevich, our Chief Commercial Officer. Eric?

接下來，我將把電話交給我們的商務長艾瑞克·貝內維奇。艾瑞克？

Thanks, Matt. I'm very proud of our team's performance last year across both CRENESSITY and INGREZZA, and I'm equally enthusiastic about the significant opportunity ahead for both brands. Matt covered the financial highlights, so I'll add additional color and highlight key focus areas to drive continued growth for both brands.

謝謝你，馬特。我為我們團隊去年在 CRENESSITY 和 INGREZZA 兩個品牌上的表現感到非常自豪，同時我也對這兩個品牌未來面臨的巨大機會充滿熱情。Matt 已經介紹了財務亮點，所以我將補充一些細節，並重點介紹推動這兩個品牌持續成長的關鍵領域。

For the CRENESSITY launch, you've heard us say so far, so great, and 2025 certainly lived up to that mantra with over $300 million of net sales in the first full year on the market. Throughout 2025, we saw strong demand across pediatric and adult patients and across both genders with prescriptions now trending towards a majority of pediatric patients in female patients on therapy.

對於 CRENESSITY 的上市，我們已經說過，到目前為止一切都很棒，而 2025 年也確實不負眾望，在上市的第一個完整年度，淨銷售額就超過了 3 億美元。2025 年全年，我們看到兒科和成人患者以及男女患者的需求都很強勁，目前處方趨勢是兒科患者佔多數，接受治療的女性患者佔多數。

Importantly, while new patient starts may vary from week-to-week and quarter-to-quarter, once the patient initiates treatment with CRENESSITY, they tend to stay on CRENESSITY. This real-world experience is consistent with our experience in the open-label extension studies. As we've said from the outset, as a first-in-disease medicine, CRENESSITY is a learning launch, very much aligned with our experience with INGREZZA in TD. In fact, the parallels between the two launches are remarkably similar.

重要的是，雖然新患者的開始治療可能每周和每季度都會有所不同，但一旦患者開始使用 CRENESSITY 進行治療，他們往往會繼續使用 CRENESSITY。這現實世界的經驗與我們在開放標籤擴展研究的經驗一致。正如我們從一開始就說過的那樣，作為首款針對該疾病的藥物，CRENESSITY 的上市是一個學習的過程，與我們在 TD 中使用 INGREZZA 的經驗非常一致。事實上，這兩次發射的相似之處非常顯著。

Both INGREZZA and CRENESSITY are first in disease therapies for conditions that previously lacked specifically FDA-approved treatment options, and both achieved approximately $300 million in sales in their first 12 months.

INGREZZA 和 CRENESSITY 都是針對以前缺乏 FDA 批准的特定治療方案的疾病療法的首創，並且在上市後的前 12 個月內，兩者的銷售額均達到了約 3 億美元。

Being a first in disease launch, we still have much to learn about the patient population, the prescriber base and potential seasonal dynamics. And similar to INGREZZA, while we're not providing specific annual guidance in year two, we remain highly confident that CRENESSITY will be Neurocrine's second blockbuster medicine as we establish it together with replacement of glucocorticoids as the standard of care treatment for patients with classic congenital adrenal hyperplasia.

由於這是該疾病領域的首例，我們對患者群體、處方醫生群體和潛在的季節性動態仍有許多需要了解的地方。與 INGREZZA 類似，雖然我們沒有提供第二年的具體年度指導，但我們仍然非常有信心，CRENESSITY 將成為 Neurocrine 的第二款重磅藥物，因為我們將與糖皮質激素替代療法一起確立為經典先天性腎上腺皮質增生症患者的標準治療方案。

As we enter CRENESSITY's second full year on the market, the natural question is, so what's next? As I noted this time last year, long-term success CRENESSITY will be driven by our ability to reach, educate and activate the CAH community on this breakthrough medicine. To date, more than 1,000 prescribers have written a prescription for CRENESSITY, yet roughly two-third have treated only one patient so far, underscoring both the progress we've made and the opportunity ahead.

隨著 CRENESSITY 進入市場第二個完整年頭，很自然地會問：接下來會發生什麼？正如我去年這個時候所指出的，CRENESSITY 的長期成功將取決於我們能否接觸、教育和動員 CAH 群體來了解這種突破性藥物。迄今為止，已有超過 1000 名處方醫生開立了 CRENESSITY 的處方，但其中約有三分之二的醫生迄今為止只治療過一名患者，這既凸顯了我們取得的進展，也凸顯了未來的機遇。

To support continued growth, we're focused on several key priorities in 2026. As previously announced, we're expanding the CRENESSITY sales force with new representatives hitting the field in April. This is a rare disease team so the overall FTE numbers are still small. However, this expansion will allow us to go deeper within the existing endocrinology HCP base and allow us to expand our reach into additional potential prescribers. While endocrinologists remain central, we've learned some classic CAH patients are managed outside of endocrinology by primary care providers or OB-GYNs.

為了支持持續成長，我們2026年將重點放在幾個關鍵優先事項上。正如先前宣布的那樣，我們將擴大 CRENESSITY 的銷售團隊，新的銷售代表將於 4 月開始上崗。這是一個罕見疾病團隊，所以全職員工總數仍然很少。然而，此次擴張將使我們能夠更深入地了解現有的內分泌醫療保健專業人員群體，並使我們能夠將業務拓展到更多潛在的處方醫生。雖然內分泌科醫生仍然發揮著核心作用，但我們了解到，一些典型的 CAH 患者是由初級保健醫生或婦產科醫生在內分泌科之外進行管理的。

We're excited to leverage AI and other technology tools to help identify and engage providers likely to be caring for classic CAH patients. We're also continuing to invest in medical education to improve the community's understanding of CAH, the limitations of GC monotherapy and reinforce CRENESSITY's compelling product profile. It remains the first and only new CAH specific treatment in 70 years. As a potent and selective CRF1 antagonist, CRENESSITY targets the source of dysregulation in CAH and directly prevents the surge of excess ACTH from the pituitary to restore downstream androgen control and enable physiologic steroid dosing.

我們很高興能夠利用人工智慧和其他技術工具來幫助識別和聯繫可能照顧經典 CAH 患者的醫療服務提供者。我們也持續投資醫學教育，以提高大眾對 CAH 的認識，了解 GC 單藥療法的局限性，並強化 CRENESSITY 的顯著產品優勢。它仍然是70年來第一個也是唯一一個針對先天性腎上腺皮質增生症的新型治療方法。作為一種強效且選擇性的 CRF1 拮抗劑，CRENESSITY 針對 CAH 的失調根源，直接阻止腦下垂體過度分泌 ACTH，從而恢復下游雄性激素控制，實現生理性類固醇劑量。

Furthermore, CRENESSITY has the largest data set in adults and children with classic CAH, which includes greater than 450 patient years of clinical trial exposure and greater than 550 patient years of real-world exposure. With a favorable long-term safety profile, robust efficacy and broad labeling, it's clear why uptake has been so strong after only one year on the market.

此外，CRENESSITY 擁有最大的經典 CAH 成人和兒童資料集，其中包括超過 450 個患者年的臨床試驗暴露和超過 550 患者年的真實世界暴露。該產品具有良好的長期安全性、強大的療效和廣泛的適應症，因此上市僅一年就獲得如此強勁的市場認可也就不足為奇了。

In fact, we estimate that we've gotten approximately 10% of the classic CAH population on therapy in the first year of availability. This is an important milestone for us. We believe as the word continues to spread in the CAH community, as the endocrinology prescriber base expands and as they share their real-world clinical experiences, we'll see a continued peer-to-peer effect that will deepen disease understanding and drive broader adoption.

事實上，我們估計在藥物上市的第一年，大約有 10% 的經典 CAH 患者接受了治療。這對我們來說是一個重要的里程碑。我們相信，隨著這一消息在 CAH 群體中不斷傳播，隨著內分泌處方醫生群體不斷擴大，隨著他們分享真實的臨床經驗，我們將看到持續的同行交流效應，這將加深對疾病的理解並推動更廣泛的應用。

Now turning to INGREZZA. We had a record number of new patient starts and a record number of total patients on therapy in 2025. Today, we estimate only about 10% of the prevalent TD population is currently taking a VMAT2 inhibitor. Even nine years since our launch, there remains a substantial opportunity to grow the class, grow our market share and help more patients start and stay on therapy.

現在轉向 INGREZZA。2025 年，我們新增患者數量和接受治療的患者總數均創歷史新高。據估計，目前只有約 10% 的 TD 患者正在服用 VMAT2 抑制劑。即使在我們推出產品九年後，仍然有很大的機會發展壯大這個行業，擴大我們的市場份額，並幫助更多的患者開始並堅持治療。

With double-digit growth momentum, strong Formulary Access and an expanded and reorganized sales force set to hit the field in Q2, a class-leading and differentiated product profile and 12 more years of remaining exclusivity, INGREZZA is well poised to help many, many more TD and HD patients.

憑藉兩位數的成長勢頭、強大的處方集准入以及即將於第二季度投入使用的擴充重組後的銷售團隊、領先且差異化的產品特性以及剩餘 12 年的獨家銷售權，INGREZZA 已做好充分準備，幫助更多 TD 和 HD 患者。

So with that, I'll turn the call over to my colleague, Dr. Sanjay Keswani, to share our pipeline progress.

那麼，接下來我將把電話交給我的同事桑傑·凱斯瓦尼博士，讓他來分享我們的研發進度。

Thanks, Eric, and good afternoon, everyone. In keeping with this year's focus on momentum and strategic diversification, our clinical organization will enroll and advance more studies than at any point in Neurocrine's history. While most of my future earnings remarks will center on enrollment progress and study initiations.

謝謝你，埃里克，大家下午好。為了配合今年的發展動能和策略多元化，我們的臨床機構將招募和推動比Neurocrine歷史上任何時期都多的研究。雖然我未來大部分的收入狀況將取決於招生進度和學習啟動。

Today, I'll highlight recently disclosed data for our two commercial assets, INGREZZA and CRENESSITY. An optimal way to compare therapies is through head-to-head studies. With that in mind, we recently published first of its kind head-to-head data comparing INGREZZA and AUSTEDO XR at the 64th Annual Meeting of the American College of Neuropharmacology.

今天，我將重點介紹我們兩項商業資產 INGREZZA 和 CRENESSITY 最近揭露的數據。比較不同療法的最佳方法是進行直接對比研究。考慮到這一點，我們最近在美國神經藥理學會第 64 屆年會上發表了首個直接比較 INGREZZA 和 AUSTEDO XR 的數據。

PET imaging results confirmed what we've long believed, not all VMAT2 inhibitors are equal. In this study, INGREZZA demonstrated a nearly twofold higher VMAT2 target occupancy compared with therapeutic doses of AUSTEDO XR, an important finding that indicates INGREZZA's superior efficacy in treating tardive dyskinesia. Turning to CRENESSITY. We recently shared data from our open-label extension study.

PET 影像結果證實了我們長期以來的看法，並非所有 VMAT2 抑制劑都一樣。在這項研究中，INGREZZA 的 VMAT2 標靶佔有率比 AUSTEDO XR 的治療劑量高出近兩倍，這一重要發現表明 INGREZZA 在治療遲發性運動障礙方面具有優越的療效。轉向 CRENESSITY。我們最近分享了我們開放標籤擴展研究的數據。

While multiple analyses are still underway and will be presented at upcoming endocrinology meetings, including ENDO 2026, the main takeaway is clear. Across both adult and pediatric CAH patients, CRENESSITY continues to show robust sustained clinically meaningful benefits through two years of treatment. We see durable reductions in excess ACTH and androgens directly addressing the underlying pathophysiology of CAH and maintaining control over time.

雖然多項分析仍在進行中，並將在即將舉行的內分泌學會議上發表，包括 ENDO 2026，但主要結論很明確。在成人和兒童 CAH 患者中，CRENESSITY 在兩年的治療中持續顯示出強勁、持久且具有臨床意義的益處。我們看到 ACTH 和雄性激素水平持續下降，直接解決了 CAH 的潛在病理生理問題，並能長期控制病情。

In pediatrics, CRENESSITY delivered sustained ACTH suppression while preserving normal physiological signaling, including the immune stress response. Hence, rates of adrenal insufficiency remained very low, zero in the pediatric double-blind study and 1.6% in adults, identical between active and placebo patients. In a prepubertal subset, we also observed slowing of bone age advancement, translating to a predicted adult height increase of over two inches.

在兒科領域，CRENESSITY 能夠持續抑制 ACTH，同時維持正常的生理訊號傳導，包括免疫壓力反應。因此，腎上腺功能不全的發生率仍然很低，在兒科雙盲研究中為零，在成人中為 1.6%，活性藥物組和安慰劑組患者之間相同。在青春期前亞組中，我們也觀察到骨齡增長速度減慢，這意味著預計成年身高將增加兩英寸以上。

In adults, approximately 70% of patients were brought into the physiological steroid range while maintaining androgen control and about 40% of overweight or obese patients achieved at least 5% weight loss over two years, reflecting CRENESSITY's beneficial cardiometabolic effects. Safety and tolerability remain excellent with approximately 80% retention at two years, no new safety signals and over 35,000 patient weeks of exposure.

在成人中，約 70% 的患者在保持雄性激素控制的同時，將類固醇水平調整到生理範圍內；約 40% 的超重或肥胖患者在兩年內至少減重 5%，這反映了 CRENESSITY 對心血管代謝的有益作用。安全性和耐受性依然良好，兩年後病患保留率約為 80%，沒有出現新的安全訊號，累積暴露患者週數超過 35,000 週。

Overall, these data reinforce CRENESSITY's strong differentiation across efficacy, safety and tolerability and support our conviction that it will continue to be the standard of care treatment for patients with classical congenital adrenal hyperplasia. Regarding our industry-leading neuropsychiatry programs, the late-stage Phase 3 studies for osavampator in major depressive disorder and direclidine in schizophrenia are enrolling well.

總體而言，這些數據強化了 CRENESSITY 在療效、安全性和耐受性方面的顯著優勢，並支持了我們的信念，即它將繼續成為經典先天性腎上腺增生症患者的標準治療方案。關於我們行業領先的神經精神病學項目，用於治療重度憂鬱症的 osavampator 和用於治療精神分裂症的 direclidine 的後期 3 期研究正在順利招募患者。

And just last month, we initiated a Phase 2 study of NBI-'890, our next-generation VMAT2 inhibitor for the treatment of tardive dyskinesia. All other studies in our portfolio are advancing as expected, and we look forward to keeping you apprised of our progress.

就在上個月，我們啟動了 NBI-'890 的 2 期研究，NBI-'890 是我們用於治療遲發性運動障礙的下一代 VMAT2 抑制劑。我們投資組合中的其他所有研究都在預期中推進，我們期待隨時向您報告我們的進展。

With that, I will hand the call back to Kyle.

這樣，我就把電話交還給凱爾了。

Thanks, I think we can go ahead and take questions now.

謝謝，我想我們現在可以開始回答問題了。

(Operator Instructions) Paul Matteis, Stifel.

（操作說明）Paul Matteis，Stifel。

Hey, good afternoon. Congrats. I appreciate that you're not guiding on CRENESSITY, but I was wondering if you could maybe give us either a window into the first six weeks of 2026 or just more broadly, the number on the revenue side, obviously way above consensus in 4Q. But as we look at start forms, there's a slight decline from 2Q to 3Q and 3Q to 4Q. Curious in your perspective on what you're seeing now and where you think this kind of patient add rate might plateau in, say, the near to midterm?

嘿，下午好。恭喜。我知道您沒有對 CRENESSITY 進行指導，但我很想知道您是否可以給我們提供一下 2026 年前六週的展望，或者更廣泛地說，提供一下收入方面的數字，顯然第四季度的收入遠高於市場普遍預期。但從開局來看，第二季到第三季以及第三季到第四季都有輕微的下降。我很想知道您對目前情況的看法，以及您認為這種患者新增率在近期或中期內可能會達到高峰嗎？

Thank you.

謝謝。

Paul, so we're going to start giving weekly sales, information out on the, on the web, just kidding. I mean it's Paul, so we're going to start giving weekly sales information out on the web. Just kidding. I mean it's been a tremendous year -- it's been a tremendous year for CRENESSITY over $300 million in the first year. Congratulations to the team. And we really look forward to year two being another strong, exciting year.

保羅，所以我們打算開始在網路上發布每週的銷售訊息，開玩笑啦。我的意思是，他是保羅，所以我們將開始在網路上發布每週的銷售資訊。只是在開玩笑。我的意思是，對於 CRENESSITY 來說，這是意義非凡的一年——第一年就取得了超過 3 億美元的收入。祝賀團隊。我們非常期待第二年也能成為同樣精彩的一年。

We do anticipate meaningful steady new patient additions every single quarter that's going to lead to a very nice growth year. We still, of course, have a whole lot to learn associated with this launch. As you remember, with INGREZZA it took us about four years to get to a guide, but we will be providing insight every quarter as it relates to net sales, demand and overall reimbursement dynamics. I'd say looking around the table, we couldn't be more proud of the team and what's been accomplished this year and really feel good with how we're positioned for the years ahead.

我們預計每季都會有顯著且穩定的新患者成長，這將帶來非常可觀的成長年。當然，關於這次發布，我們還有很多東西要學習。如您所知，我們花了大約四年時間才制定 INGREZZA 的指導方針，但我們將每個季度提供與淨銷售額、需求和整體報銷動態相關的見解。環顧四周，我們為團隊以及今年的成就感到無比自豪，並且對我們未來幾年的發展前景感到非常滿意。

Cory Kasimov, Evercore ISI.

Cory Kasimov，Evercore ISI。

Hey, good afternoon, guys. Thanks for taking my question. I wanted to ask about that receptor occupancy poster from late January regarding INGREZZA versus AUSTEDO. Curious how you might use this information? And what are the potential implications here with regard to your next-gen VMAT2 inhibitors?Thank you.

嘿，各位下午好。謝謝您回答我的問題。我想問一下一月底發布的關於 INGREZZA 與 AUSTEDO 的受體佔有率海報。想知道您會如何利用這些資訊嗎？那麼，這對你們的下一代VMAT2抑制劑可能意味著什麼？謝謝。你。

Yes. So we're quite excited by the data we showed, which is essentially a head-to-head PET study between AUSTEDO XR and INGREZZA. And as we articulated in our recent press release, we saw nearly double the target occupancy for INGREZZA after one dose versus AUSTEDO XR.

是的。我們對展示的數據感到非常興奮，這本質上是 AUSTEDO XR 和 INGREZZA 之間的一項直接 PET 研究。正如我們在最近的新聞稿中闡述的那樣，我們發現，與 AUSTEDO XR 相比，INGREZZA 在單劑給藥後靶點佔有率幾乎翻了一番。

And even when we measured at steady-state concentrations, we still had a markedly superior advantage in terms of VMAT2 target engagement. We think this underlines the efficacy that we see in INGREZZA in the community of patients with tardive dyskinesia as our belief is that the higher the rate of VMAT2 target occupancy, the greater the efficacy in terms of control of tardive dyskinesia.

即使我們測量的是穩態濃度，我們在 VMAT2 標靶結合方面仍然具有明顯的優勢。我們認為這突顯了我們在 INGREZZA 治療遲發性運動障礙患者群體中看到的療效，因為我們相信 VMAT2 標靶佔據率越高，在控制遲發性運動障礙方面的療效就越好。

In terms of the second part of your question, we clearly have a lot of experience in terms of matching receptor occupancy with clinically efficacious doses. And we're utilizing that relationship with our two VMAT2 follow-ons. Indeed, we started a Phase 2 study of our first follow-on in tardive dyskinesia quite recently.

關於您問題的第二部分，我們在將受體佔有率與臨床有效劑量相匹配方面顯然有很多經驗。我們正在利用這種關係進行兩項 VMAT2 後續研究。事實上，我們最近啟動了針對遲發性運動障礙的首個後續研究的第 2 期臨床試驗。

Phil Nadeau, TD Cowen.

菲爾·納多，TD·考恩。

Good afternoon. Thanks for taking our questions and congratulations on a productive year. I just want to follow up on Paul's question on patient dynamics with CRENESSITY. I think in your prepared remarks, you mentioned the possibility of seasonality in patient demand.

午安.感謝您回答我們的問題，並祝賀您度過了碩果累累的一年。我只是想就保羅提出的關於 CRENESSITY 患者動態的問題做個後續說明。我認為您在事先準備好的演講稿中提到了患者需求可能存在季節性波動。

And I think investors were all debating whether there could have been an early launch bolus to patient initiations. Appreciating that you still have a lot to learn, what have you learned about those two factors and patient dynamics, one in early launch bolus and two, whether there's any seasonality as you go through the year?

我認為投資者們都在爭論是否可以提前推出產品以促進患者啟動治療。考慮到您還有很多東西要學習，您對這兩個因素和患者動態有什麼了解？一個是早期啟動推注，另一個是全年是否有季節性變化？

Yes. Thanks, Phil. This is Kyle. Good question here on that. I think it's important to keep in mind that the similarities that Eric called out in his opening remarks here are quite true and accurate across the Board.

是的。謝謝你，菲爾。這是凱爾。問得好。我認為重要的是要記住，埃里克在開場白中提到的那些相似之處在各個方面都是非常真實和準確的。

In terms of the first year of launch, we've gone through our first Q1 through Q4. As we've learned in most orphan diseases and launches, whether it was INGREZZA or looking at others, there's always ebbs and flows in enrollment forms. And in particular, early in launch, it's typically a function of frequency of office visits when patients initially hear about the opportunity for a new medicine and physicians getting the word out.

就產品上市第一年而言，我們已經度過了第一季到第四季。正如我們在大多數罕見疾病和藥物上市過程中所了解的，無論是 INGREZZA 還是其他藥物，註冊表格的填寫情況總是會有起伏。尤其是在上市初期，這通常取決於患者首次聽到新藥機會以及醫生宣傳新藥的頻率。

So I think it's too early to call whether or not there's any seasonality component. It takes a couple of quarters to draw those conclusions across multiple years. And it took us a while to get to that level of confidence with INGREZZA. So I think it's prudent right now to collect that information and make a more sound decision about guidance, enrollment forms, things of that sort as we get a little bit further in the launch.

所以我覺得現在判斷是否有季節性因素還太早。要得出跨越多年的結論，需要幾個季度的時間。我們花了很長時間才對 INGREZZA 建立起這種程度的信心。所以我認為，現在明智的做法是收集這些信息，並在專案啟動的後續階段，就指導方針、報名表等事項做出更合理的決定。

But rest assured, great feedback out there across all the stakeholders, prescribers, physicians and even payers out there. So nothing out there is saying that we're anywhere but moving towards changing the standard of care and achieving blockbuster status like we've done with INGREZZA.

但請放心，所有利害關係人，包括處方醫生、醫師甚至支付方，都給予了很好的回饋。所以目前沒有任何跡象表明，我們正朝著改變護理標準和實現像 INGREZZA 那樣的轟動性目標邁進。

Brian Abrahams, RBC Capital Markets.

Brian Abrahams，加拿大皇家銀行資本市場。

Hey, guys, thanks for taking my question and my congrats as well on a very productive year. Question on the expense side. It seems like you're expecting a little bit of an uptick in R&D expenses for this year relative to 2025. Can you talk a little bit more about the components of that? How much of that is some of the earlier-stage programs like obesity? And how quickly could some of those costs potentially roll off in 2027 once the Phase 3s readout?

嘿，各位，感謝你們回答我的問題，也恭喜你們度過了碩果累累的一年。關於費用方面的問題。看來您預計今年的研發支出將比 2025 年略有成長。能再詳細談談它的組成部分嗎？其中有多少是早期階段的項目，例如肥胖症項目？而一旦第三階段試驗結果在 2027 年公佈，其中一些成本可能會以多快的速度下降？

Yes. Thank you for the question. The cost increase is really on the heels of the Phase 3 trials and pushing those forward for a full year this year in 2026. The obesity investment is actually quite minimal for 2026, but of course, is a really important program for us to be able to drive shareholder value creation, which we would expect some level of data in '27. But from an expense, when do expenses roll off, we would anticipate for the major Phase 3 programs. Those will carry on through 2027 with a big chunk falling off in 2028.

是的。謝謝你的提問。成本增加實際上是由於 3 期試驗的推進，並將試驗提前至 2026 年進行，為期一年。2026 年在肥胖問題上的投資實際上非常少，但當然，這對我們來說是一個非常重要的項目，能夠推動股東價值創造，我們預計在 2027 年會有一些相關數據。但從支出角度來看，支出何時會減少？我們預計主要第三階段項目將會出現這種情況。這些趨勢將持續到 2027 年，其中很大一部分將在 2028 年消失。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi guys, thanks for taking my question. I wanted to go back to CRENESSITY for a second. So I know it took, what is it, three or four years before you guys started giving guidance on INGREZZA. What kind of metrics did you need to collect in order to get confident in providing guidance? And do you have a sense of whether or not it would take that length of time before you get confident with CRENESSITY and providing sales guidance for that as well?

大家好，感謝你們回答我的問題。我想再回到 CRENESSITY 一會兒。所以我知道，你們花了三、四年才開始提供 INGREZZA 的指導。為了能夠自信地提供指導，你需要收集哪些指標？您是否預估過，需要多長時間才能對 CRENESSITY 充滿信心，並能為其提供銷售指導？

Yeah, hi, Tazeen, maybe I'll tackle the second question first. It may not take as long to get to a point where we feel comfortable giving guidance with CRENESSITY as it did with INGREZZA. This is a rare disease. INGREZZA is not a rare disease, but it was at the time, a rarely diagnosed disease. We have a single -- essentially a single prescriber base in endocrinology versus multiple different specialties and different sites of care and so on, which made getting a handle on INGREZZA a little bit more challenging early on.

嗨，塔津，或許我可以先回答第二個問題。我們或許不會像當初使用 INGREZZA 那樣，花那麼長時間才能感到能夠安心地為 CRENESSITY 提供指導。這是一種罕見疾病。INGREZZA 不是一種罕見疾病，但在當時卻是一種很少被診斷出來的疾病。我們內分泌科只有一個處方醫生群體，而其他科室則有多個不同的專科和不同的醫療機構等等，這使得早期掌握 INGREZZA 的相關資訊更具挑戰性。

As I mentioned in my prepared remarks, both are first-in-disease therapies, both are breakthrough medicines. But as Kyle stated, we've gone through one cycle so far with CRENESSITY in classic CAH and it has been a learning launch for us. There's a few factors that have been a little bit different than what we expected, but different in the positive. The adoption rate was greater than what we had expected coming into this launch, which is awesome. Certainly, the reimbursement has been favorable, and we've been very pleased with the persistency that we've seen when patients start treatment, they tend to stay on it.

正如我在準備好的演講稿中提到的，這兩種療法都是針對疾病的首創療法，都是突破性藥物。但正如 Kyle 所說，到目前為止，我們已經在經典 CAH 中完成了 CRENESSITY 的一個週期，這對我們來說是一次學習性的發布。有些因素與我們的預期略有不同，但都是正面的不同。這次產品發布後的用戶採納率超出了我們的預期，這真是太棒了。當然，報銷情況令人滿意，而且我們對病人的堅持治療非常滿意，他們一旦開始治療，往往就能堅持下去。

So as we get more experience in this community in the CAH community and as we learn more about how we're able to reach sort of beyond that first 10% of the population that I talked about, then I think we'll get to a point down the road where we feel more comfortable providing specific guidance.

因此，隨著我們在 CAH 社群中累積更多經驗，並更多地了解如何能夠接觸到我剛才提到的最初 10% 的人群之外的人，我認為，在未來的某個時候，我們會更有信心提供具體的指導。

Let's not confuse not providing guidance with not expecting significant growth this year. Everything that we see from steady enrollments of new patients along with patients staying on therapy, everything points to there continuing to be strong growth. It's just a company decision that we made to not provide a guide here.

不要把不提供業績指引與不預期今年會有顯著成長混為一談。從新患者穩定入組以及患者堅持治療的情況來看，一切都顯示成長動能將持續強勁。這是我們公司做出的不提供指南的決定。

Corinne Johnson, Goldman Sachs.

科琳·約翰遜，高盛集團。

Thanks, and good afternoon. I guess beyond the pricing discussion with respect to INGREZZA and AUSTEDO, which I guess is now better understood, how are you thinking about volume impact to INGREZZA next year with AUSTEDO becoming a negotiated product? And how do you think formularies are going to handle here in products in the context of maybe more like relatively competitive pricing than we could have expected?

謝謝，下午好。我想，除了關於 INGREZZA 和 AUSTEDO 的定價討論（我想現在大家對定價有了更清晰的了解）之外，您認為 AUSTEDO 成為協商產品後，明年 INGREZZA 的銷量會受到怎樣的影響？您認為在產品定價可能比我們預期的更具競爭力的情況下，藥品目錄將如何因應？

Yes. I mean, obviously, we've been thinking and preparing for the 2027 formulary year and the impact of deuterated tetrabenazine having an MFP negotiated price. But certainly, we're very focused on 2026 as we kind of prepare to go into that next phase. We're in a position now, and Kyle talked about it with his prepared remarks of carrying a lot of momentum into 2026 in terms of our volume growth and new patient starts, having favorable coverage, especially in the Medicare formularies and being able to leverage all of that as we enter into the formulary negotiations for 2027.

是的。我的意思是，很顯然，我們一直在思考和準備 2027 年的藥品目錄年度以及氘代四苯嗪透過藥品目錄協商價格所產生的影響。但可以肯定的是，我們非常關注 2026 年，因為我們正在為進入下一階段做準備。我們現在所處的位置，正如凱爾在事先準備好的發言中談到的那樣，在 2026 年，我們在業務量增長和新患者數量方面都保持著強勁的勢頭，擁有有利的覆蓋範圍，尤其是在醫療保險處方集方面，並且能夠在進入 2027 年處方集談判時利用所有這些優勢。

So we feel good about our strategy for 2027. We believe we'll be able to maintain formulary coverage to enable continued growth. And this is a market that has been growing at a double-digit clip for the last several years, which is pretty amazing, especially for a category that's coming into year nine, year 10. So we feel good about 2026, expect to have another really strong year for INGREZZA, and we feel good about our strategy for maintaining that growth in 2027 and beyond.

因此，我們對2027年的策略感到滿意。我們相信能夠維持藥品目錄覆蓋範圍，從而實現持續成長。過去幾年，這個市場一直保持著兩位數的成長速度，這非常了不起，尤其是對於一個即將進入第九年、第十年的類別來說。因此，我們對 2026 年充滿信心，預計 INGREZZA 將迎來又一個強勁的年份，並且我們對在 2027 年及以後保持增長的戰略充滿信心。

And the only thing I would add to that, this is Kyle, by the way, is that on the 2026, we have our contracting done that we pulled through in 2025. So we expect that to be stable this year, no midyear adds like we saw in 2025. So entering '26, we expect the net revenue per prescription to be roughly similar throughout the course of the year.

我唯一要補充的是，我是凱爾，關於 2026 年，我們已經完成了 2025 年完成的合約。因此我們預計今年情況會比較穩定，不會像 2025 年那樣在年中增加。因此，進入 2026 年，我們預計全年每張處方的淨收入將大致保持不變。

So revenue growth should also track nicely volume growth this year. That's our expectation. So a strong year here like in 2025, we expect good double-digit volume growth and to increase our market share throughout the course of the year.

因此，今年的營收成長也應該會與銷售成長保持良好的同步。這是我們的預期。因此，如果像 2025 年一樣，今年業績強勁，我們預計銷量將實現兩位數成長，並在年內提高市場份額。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

Hey guys, Congrats on all the progress. We're curious about the 569 study in Alzheimer's psychosis and any potential lessons learned from the ADEPT-2 study of Cobenfy, especially in terms of managing trial conduct across the study sites and any strategies you can use to mitigate operational risks for that study? Thank you.

各位，恭喜你們所取得的所有進展。我們很想了解阿茲海默症精神病的 569 研究，以及從 Cobenfy 的 ADEPT-2 研究中可能吸取的任何經驗教訓，尤其是在管理跨研究中心的試驗開展方面，以及您可以採取哪些策略來降低該研究的營運風險？謝謝。

Yes. We are watching the progress of Cobenfy in AD psychosis quite carefully. But just as an aside, psychiatry studies deserve specific attention. And we are fortunate to have a very experienced team who've successfully executed psychiatry studies. So, for both our Phase 3 studies, we spent a lot of time carefully selecting sites and ensuring that the patients enrolled in our studies are real patients rather than professional patients who may inflate a placebo response.

是的。我們正在密切關注Cobenfy在阿茲海默症精神病治療中的進展。但順便提一下，精神病學研究值得特別關注。我們很幸運擁有一支經驗豐富的團隊，他們成功地進行了精神病學研究。因此，在我們的兩項 3 期研究中，我們花費了大量時間精心挑選試驗地點，並確保參與我們研究的患者是真正的患者，而不是可能誇大安慰劑效應的專業患者。

And indeed, with respect to placebo mitigation, we have a multifold strategy with respect to design of the study, one-to-one randomization, keeping the study sites relatively small. So for example, we only have 20 sites per Phase 3 study for direclidine in our schizophrenia studies. And also, a great deal of hands-on monitoring of sites and site investigators by our internal team. So I think the BMS data were invited some caution with respect to ensuring that we adequately monitor these sites, but we feel in a pretty good position in terms of doing that already.

確實，為了減輕安慰劑效應，我們在研究設計方面採取了多方面的策略，包括一對一隨機化，以及保持研究中心相對較小。例如，在我們的精神分裂症研究中，direclidine 的每個 3 期研究只有 20 個研究中心。此外，我們的內部團隊也對現場和現場調查人員進行了大量的實地監督。所以我認為，BMS 數據需要我們謹慎對待，以確保我們能夠充分監測這些站點，但我們感覺在這方面我們已經處於相當有利的地位。

Anupam Rama, JPMorgan.

Anupam Rama，摩根大通。

Hi, this is Joyce on for Anupam. Could you discuss the feedback you've been getting from KOLs about your two-year CRENESSITY data, specifically as it relates to durability of benefit and just how you see this data continuing to support and drive strong persistence of patients on drug? Thank you.

大家好，我是Joyce，替Anupam為您報道。您能否談談您從關鍵意見領袖那裡得到的關於您兩年 CRENESSITY 數據的反饋，特別是關於療效持久性方面的反饋，以及您認為這些數據將如何繼續支持和推動患者堅持服用該藥物？謝謝。

Yes. So we've been getting a lot of positive support from clinicians who have been prescribing CRENESSITY, as you say, for some time now. And we recently showed that two-year data and again, listed a lot of positive feedback. I think what's important for these patients and often their parents is showing that androgens are reduced in a chronic fashion.

是的。正如你所說，我們已經從臨床醫生那裡得到了很多積極的支持，他們已經開立 CRENESSITY 處方一段時間了。我們最近公佈了兩年的數據，並再次列出了許多正面的回饋。我認為對於這些患者以及他們的父母來說，重要的是要證明雄性激素水平已經長期降低。

And by doing so, reducing doses of glucocorticoids to physiological levels. And that's a huge deal for this patient population who are essentially plagued by the side effects of chronic glucocorticoid use. So in our two-year data set, we saw reductions in weight for those individuals who are obese, improved insulin tolerance.

這樣做可以將糖皮質激素的劑量降低到生理水平。對於長期使用糖皮質激素而飽受副作用困擾的患者族群來說，這意義重大。因此，在我們兩年的資料集中，我們發現肥胖者的體重有所減輕，胰島素耐受性有所改善。

And with respect to androgen suppression, we also saw attenuation of bone age advancement and that's a big deal for these patients. And again, their parents because often these individuals have precocious puberty and don't attain the potential with respect to adult height. So really pleased to see that data and also the positive impact on the community.

至於雄性激素抑制，我們也觀察到骨齡增長減緩，對這些患者來說意義重大。再次強調，他們的父母也難辭其咎，因為這些個體往往性早熟，無法達到成年身高的預期。看到這些數據以及對社區的正面影響，我真的很高興。

Lastly, I'll say that the drug is actually really well tolerated, very important, particularly in a pediatric population. So no surprises at all despite collecting over 35,000 patient weeks of exposure. Of note, we do preserve the vasopressin-induced ACTH stimulus. I mentioned that because adrenal insufficiency is always a worry, particularly as you reduce glucocorticoids. And we're very happy with that adrenal insufficiency data. Indeed, no cases in the pediatric population and an active versus placebo rate that was equivalent in the adult population. So hopefully, that addressed your question.

最後，我想說的是，這種藥物的耐受性非常好，這一點非常重要，尤其是在兒科族群。所以，儘管收集了超過 35,000 個患者週的暴露數據，但結果卻絲毫沒有出乎意料。值得注意的是，我們保留了加壓素誘導的 ACTH 刺激。我之所以提到這一點，是因為腎上腺功能不全總是一個令人擔憂的問題，尤其是在減少糖皮質激素的情況下。我們對腎上腺功能不全的數據非常滿意。事實上，兒科族群中沒有病例，且成人族群中活性藥物與安慰劑的發生率相當。希望這能解答你的疑問。

Yes. This is Kyle. Maybe just to add 2 quick comments on there. I think the pieces that are really important is if you think about safety and tolerability, the open-label extension, 90% of subjects rolled over and then 80% out to two years. Just an amazing safety and tolerability profile.

是的。這是凱爾。或許我還要補充兩點。我認為真正重要的部分是，如果你考慮安全性和耐受性，開放標籤擴展研究，90% 的受試者繼續參與研究，然後 80% 的受試者參與研究長達兩年。安全性和耐受性都非常好。

In CAH, although you could say this about many disease states more so than ever for CAH, efficacy gets your foot in the door, but safety and tolerability wins the day. I think the other piece is on the efficacy that we see at two years, it really describes the benefits of long-term treatment. You can really bend the course of the disease in terms of progression. The earlier you treat, the younger you are and the longer you stay on treatment. So all good things to think about when we continue to accumulate this longer-term data.

在 CAH 中，雖然這句話也適用於許多疾病狀態（尤其對 CAH 而言），療效是敲開大門的第一步，但安全性和耐受性才是最終的決定因素。我認為另一部分是關於兩年後療效的，它真正描述了長期治療的好處。你可以真正改變疾病的進展。治療越早，年齡越小，治療時間也越長。所以，當我們持續累積這些長期數據時，這些都是值得思考的好問題。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

Great, thank you very much for taking my question. So one is regarding the expenses on the SG&A side. It seems like the sales and marketing increase is more than what we have seen last year. Can you just help us understand is it more towards CRENESSITY or INGREZZA?

太好了，非常感謝您回答我的問題。其中一個問題涉及銷售、一般及行政費用方面。銷售和行銷方面的成長似乎比去年同期要多。您能幫我們理解一下，它更偏向 CRENESSITY 還是 INGREZZA 嗎？

And then I would also love to understand how you're thinking about INGREZZA given that you are guiding for a 10% growth, which is higher than last year. So do you expect volumes to continue to grow at the rate of last year? Or it's just like you're not seeing price decline this year. So that's probably what is driving it? Thank you.

另外，鑑於您預計 INGREZZA 的成長率為 10%，高於去年，我也很想了解您對 INGREZZA 的看法。那麼你預計銷售量會繼續以去年的速度成長嗎？或者就像你今年根本沒看到價格下跌一樣。所以這很可能就是背後的驅動因素？謝謝。

So SG&A expense is really the sales force expansion that we mentioned on the last call is a significant part of that. And we also have other ancillary initiatives surrounding CRENESSITY as well as INGREZZA to ultimately drive sales. But this coming year, we do expect double -- or this year, we expect double-digit growth, as we've said. That's partially offset by price, call it, negative 4% based upon the pricing that we -- the contracting that we had entered into in the first half of last year.

所以，銷售、一般及行政費用其實就是我們在上次電話會議中提到的銷售團隊擴張，這是其中很大一部分。此外，我們還有圍繞 CRENESSITY 和 INGREZZA 的其他輔助舉措，最終目的是推動銷售。但正如我們所說，我們預計明年將實現兩位數的成長。價格方面，這部分被抵消了，可以說是負 4%，這是根據我們去年上半年簽訂的合約價格計算的。

So you're talking about volume growth at the midpoint of our guidance range for INGREZZA to be in the mid-teens. So we feel really good with where the team is positioned. And of course, with the sales force expansion going to be in place at the end of Q1, we'd expect to see more benefit in the second half of the year.

所以您指的是INGREZZA的銷售成長將達到我們預期範圍的中點，即十幾個百分點。所以我們對球隊目前的狀況非常滿意。當然，隨著銷售團隊的擴張將在第一季末完成，我們預計下半年將看到更多收益。

Myles Minter, William Blair.

邁爾斯·明特，威廉·布萊爾。

Hey, thanks guys. I just had a question on the number of Tuesdays in each quarter. I'm actually going to ask about the sales force expansion for CRENESSITY onboard in April. Is that required to keep this steady new patient flow in for the product? Or would you expect sometime in the second half of the year maybe that, that sales force expansion helps inflect the product? Thanks.

嘿，謝謝大家。我只是想問一下每個季度有多少個星期二。我打算在四月詢問一下 CRENESSITY 的銷售團隊擴充。這樣做是為了維持該產品穩定的新患者來源嗎？或者您是否預計，在今年下半年某個時候，銷售團隊的擴張將有助於對產品產生影響？謝謝。

Yes. The way I would characterize it is that we're investing in growth. We're very optimistic about the opportunity with CRENESSITY in classic CAH. And we made our sales force size and structure decisions prior to the launch without the sort of, I'll call it, the Monday morning quarterback opportunity of having more data to work with.

是的。我的理解是，我們正在投資成長。我們對 CRENESSITY 在經典 CAH 領域的機會非常樂觀。我們在產品發布前就制定了銷售團隊的規模和結構決策，而沒有像「事後諸葛亮」那樣，擁有更多的數據來分析問題。

So obviously, we have been executing this expansion on a relative basis. It's not a large number of FTEs that we're adding into the CRENESSITY team, but we do think it will allow us to do a couple of things. One is to go deeper within the existing prescriber base. And in my prepared remarks, I talked about how we now have over 1,000 doctors that have prescribed CRENESSITY and yet two-third of them have only treated one patient thus far. So we know that there's more patients in those practices. And given the very large territory sizes, this will allow us to get in and follow up with the existing prescribers a little bit more frequently.

顯然，我們一直以來都是以相對的方式進行擴張的。雖然我們為 CRENESSITY 團隊增加的 FTE 數量不多，但我們認為這將使我們能夠做一些事情。一種方法是深入挖掘現有處方醫生群體。在我的發言稿中，我談到現在有超過 1000 名醫生開過 CRENESSITY 處方，但其中三分之二的醫生迄今為止只治療過一名患者。所以我們知道這些診所的病人比較多。鑑於轄區面積非常大，這將使我們能夠更頻繁地與現有處方醫生進行後續追蹤。

Secondly, we also recognize that there are some patients out there that we haven't been able to reach through the existing sales team. So we can go deeper into endocrinology, and we recognize that some patients are not cared for by an endocrinologist. They might be seeing an internal medicine or a family medicine physician or even an OB/GYN. So we have the opportunity now to explore that a little bit with the expanded sales team.

其次，我們也意識到，我們現有的銷售團隊還無法接觸到某些患者。因此，我們可以更深入地了解內分泌學，並且我們認識到有些患者並沒有得到內分泌科醫生的治療。他們可能會去看內科醫生、家庭醫生，甚至是婦產科醫生。所以現在我們有機會和擴大的銷售團隊一起對此進行一些探索。

Last thing I'll say is that we're excited about the reputation that we've created within the endocrinology community. We're able to attract some really high potential and I think people with great track records onto the team. We've actually completed the expansion of that group. They're going through training now and we'll be ready to deploy into the new organizational structure at the beginning of Q2. So full steam ahead with the expansion and certainly very excited about the additional bandwidth that we'll have created as we execute against it.

最後我想說的是，我們對在內分泌學界建立的聲譽感到非常興奮。我們能夠吸引一些極具潛力且擁有出色業績的人才加入團隊。我們已經完成了該團隊的擴充。他們現在正在接受培訓，我們將在第二季初準備好部署到新的組織結構。因此，我們將全力推動擴建計劃，並且對實施過程中將獲得的額外頻寬感到非常興奮。

So, Myles, I'll be holding a webinar about the calendar and how it lays out the rest of the year. Just kidding, but I did want to go back to a question that Phil had regarding CRENESSITY seasonality, and I think Kyle and Eric addressed it nicely in terms of not having enough experience with CRENESSITY demand side.

邁爾斯，我將舉辦一場關於日曆及其如何安排今年剩餘時間的線上研討會。開玩笑啦，不過我確實想回到 Phil 之前提出的關於 CRENESSITY 季節性的問題，我認為 Kyle 和 Eric 已經很好地回答了這個問題，因為他們在 CRENESSITY 需求方面經驗不足。

I meant to mention there is a gross to net impact in the first quarter. It's about 5%, and it's associated with the commercial co-pay reset. So that's one thing I wanted to make sure as you're developing your models and expectations for Q1 for CRENESSITY, that would be something that you take into consideration. Thanks.

我本來想提一下，第一季存在毛利潤與淨利的轉換。大約是 5%，這與商業共同支付重置有關。所以，我想確保的是，當您為 CRENESSITY 制定第一季模型和預期時，這一點您需要考慮。謝謝。

Yigal Nochomovitz, Citigroup.

Yigal Nochomovitz，花旗集團。

Hi, great, thank you and congrats on all the progress. I just wanted to probe a little further on the 10% share in CAH. Is it correct that that's all endos? Are you seeing any early share from some of the other categories you mentioned like PCPs and OB/GYN. And I'm wondering to what extent at this point you can use some of the AI database inferencing to sort of tease out which PCPs and OB/GYNs may be the best candidates for CRENESSITY?

您好，太好了，謝謝，也恭喜您取得的所有進展。我只是想進一步探討 CAH 的 10% 股份的情況。是不是所有內分泌腫瘤都包含在內了？您提到的其他類別（例如全科醫生和婦產科醫生）是否有任何早期市場份額？我想知道，目前您可以在多大程度上利用人工智慧資料庫推理來篩選出哪些全科醫生和婦產科醫生可能是 CRENESSITY 的最佳候選人？

Yes. So yes, I just want to clarify when -- in my prepared remarks, I talked about the fact that we estimate that we've reached and gotten on board treatment of approximately 10% of the prevalent CAH population. So taking a step back, in the US, we estimate it's around 20,000 people with classic CAH. And obviously, in year one to get to about 10% of them and get them on treatment is a really important milestone for us. Virtually all of those new patient starts have been originated within endocrinology.

是的。是的，我只是想澄清一下——在我準備好的演講稿中，我談到我們估計已經接觸並接受了大約 10% 的 CAH 患者的治療。所以退一步說，在美國，我們估計大約有 20,000 人患有經典型先天性腎上腺皮質增生症 (CAH)。顯然，在第一年，能夠接觸到大約 10% 的患者並讓他們接受治療，這對我們來說是一個非常重要的里程碑。幾乎所有新增患者都來自內分泌科。

And we recognize that for us to be able to continue to expand the use of CRENESSITY and get broader within that patient population, we're going to have to be able to reach patients beyond the prescriber base that we've reached thus far. And you mentioned patient finding. I talked about that a little bit in my prepared remarks.

我們認識到，為了能夠繼續擴大 CRENESSITY 的使用範圍，並在患者群體中獲得更多益處，我們必須能夠接觸到我們迄今為止所接觸到的處方醫生群體之外的患者。你提到了尋找患者。我在事先準備好的發言稿中稍微談到了這一點。

So we are leveraging different technology platforms and different data sets that will allow us to identify where are patients that look similar, at least in the data to the patients that we've already gotten on treatment and then allow our field sales organization to follow up and to confirm whether those patients exist at this or that practice. Using that information and feeding it back makes the system smarter and allows us to improve our targeting.

因此，我們正在利用不同的技術平台和不同的數據集，以便識別出哪些患者看起來與我們已經接受治療的患者相似（至少在數據上如此），然後讓我們的現場銷售組織跟進並確認這些患者是否存在於某個診所。利用這些資訊並回饋給系統，可以使系統更智能，並使我們能夠改善目標定位。

So this is a rare disease, and there isn't a specific diagnosis code for classic CAH. And so, for us to continue to grow and to have that steady growth that we expect, we have to leverage technology, and we also have to leverage the team.

所以這是一種罕見疾病，而且經典型先天性腎上腺皮質增生症沒有特定的診斷代碼。因此，為了繼續發展並實現我們所期望的穩定成長，我們必須利用技術，也必須利用團隊的力量。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Thanks. Maybe I'll ask another CRENESSITY question, but a different way. As you think about furthering penetration, are you getting any kind of pushback from endocrinologists? Or maybe I'll ask differently, what -- are there any barriers to further adoption that you're seeing?

謝謝。也許我會換個方式再問一個關於 CRENESSITY 的問題。在考慮進一步擴大市場滲透率時，您是否從內分泌學家那裡得到任何阻力？或者我換個方式問，您認為在進一步推廣應用程式上有哪些障礙？

And also, as you think about the competitor that's in development, the ACTH antagonist, do you have a sense that doctors are waiting out the availability of that drug to put patients on that modality as opposed to CRENESSITY. Maybe you can talk about that dynamic as well. Thank you.

另外，考慮到正在研發中的競爭對手 ACTH 拮抗劑，您是否覺得醫生們正在等待這種藥物上市，以便讓患者接受這種療法而不是 CRENESSITY？或許你也可以談談這種動態。謝謝。

Yes. Maybe I'll tackle the second question first. The answer is no. I don't think that community endocrinologists are for the most part, aware of an investigational drug or are warehousing or holding back treatment of patients for a drug that may or may not be available several years down the road. In terms of what's the biggest barrier, I would say it's lack of knowledge.

是的。或許我可以先回答第二個問題。答案是否定的。我認為大多數社區內分泌學家並不了解試驗性藥物，也不會為了等待幾年後可能上市也可能不上市的藥物而囤積或延遲治療病人。要說最大的障礙是什麼，我認為是缺乏知識。

And the reason I say that is that, yes, there are some endocrinologists that are quite familiar with and skilled in managing these patients. But the vast majority of community endocrinologists have little experience with classic CAH. And if they have CAH patients in their practice, they might have a couple of them. And so a big part of our educational effort, I mentioned this in my prepared remarks, is really continuing to educate around classic CAH, the inadequacies of high-dose glucocorticoid treatments, the consequences of patients being either over or undertreated and then tying that back to the clinical profile that's emerged for CRENESSITY, especially the very strong safety and tolerability that we've seen both in the trials and in the real-world experience.

我之所以這麼說，是因為確實有些內分泌學家非常熟悉並擅長治療這類患者。但絕大多數社區內分泌科醫師對經典型先天性腎上腺皮質增生症 (CAH) 缺乏經驗。如果他們診所裡有 CAH 患者，他們可能會遇到幾個。因此，正如我在準備好的發言稿中提到的，我們教育工作的一個重要部分是繼續圍繞經典 CAH 進行教育，強調高劑量糖皮質激素治療的不足，以及患者治療過度或不足的後果，並將這些與 CRENESSITY 的臨床特徵聯繫起來，特別是我們在試驗和真實世界經驗中看到的非常強的安全性和耐受性。

So it's really getting physicians past this sort of, I'll call it, pre-CRENESSITY belief that they're treating their patients with these steroids. They think they're doing fine. But when they look closer, they realize that they're having a lot of comorbidities and a lot of complications from either their disease or from their GCs. And as we continue to make that education more broad, certainly, we're seeing that doctors are realizing that, hey, CRENESSITY is a whole new way of treating CAH. It's a paradigm shift. And I think that, that's been borne out in the adoption.

所以，它真正幫助醫生剋服了這種我稱之為“CRENESSITY 之前的觀念”，即他們正在用這些類固醇治療病人。他們覺得自己做得很好。但仔細觀察後，他們發現自己患有多種合併症，而這些併發症可能是由他們的疾病或胃癌引起的。隨著我們不斷擴大教育範圍，我們當然看到醫生們意識到，CRENESSITY 是一種治療 CAH 的全新方法。這是範式轉移。我認為，收養情況已經證實了這一點。

The other thing that I'll say is that we've been working really closely with the patient advocacy group, the CARES Foundation. They've been a wonderful partner in terms of educating their membership. And certainly, coming into this launch, we recognize that a lot of patients with CAH or families with CAH didn't fully understand the consequences of either uncontrolled androgens and/or excess glucocorticoid exposure. And so we continue to direct our educational efforts, not just towards HCPs, but also towards the patient community, and I think it's really a benefit to both groups.

我還要補充一點，我們一直與病患權益倡議組織 CARES 基金會密切合作。在會員教育方面，他們一直是非常棒的合作夥伴。當然，在推出這款產品之前，我們也意識到許多患有 CAH 的患者或 CAH 患者家庭並沒有完全了解不受控制的雄性激素和/或過量糖皮質激素暴露的後果。因此，我們繼續將教育工作重點放在醫療保健專業人員以及患者群體上，我認為這對這兩個群體都有好處。

Brian Skorney, Baird.

Brian Skorney，Baird。

Hi team, thanks for the question. This is Luke on for Brian. So on CRENESSITY, with regard to the remaining estimated 90% untreated prevalent market, can you remind us what proportion is managed at an endocrinologist compared to primary care or other settings?

大家好，感謝你們的提問。這是盧克替布萊恩報道。那麼，關於 CRENESSITY，對於剩餘的估計 90% 未治療的患病市場，您能否提醒我們，與初級保健或其他機構相比，內分泌科醫生治療的比例是多少？

Yes. I think we're learning that. And so it's difficult to give you an exact proportion of what proportion are under the care of an endo versus a PCP. And one of the things that we've seen at least in the cohort of patients that have been started already on CRENESSITY is that some of them appear to be co-managed by endocrinologists and primary care. And it may be that they see their endocrinologists once a year, but they may be seeing their primary care physician more frequently in the questions who's managing their CAH and refilling their prescriptions and so on.

是的。我認為我們正在逐漸認識到這一點。因此，很難給出由內分泌科醫生治療的患者與初級保健醫生治療的患者之間的確切比例。至少在已經開始接受 CRENESSITY 治療的患者群體中，我們看到的一件事是，其中一些患者似乎是由內分泌科醫生和初級保健醫生共同管理的。他們可能每年只去看一次內分泌科醫生，但可能會更頻繁地去看他們的初級保健醫生，詢問誰在管理他們的 CAH 以及續開他們的處方等等。

So as we go forward, teasing that out of the data, I think, is really important. And I think that, as I mentioned earlier, being able to identify those primary care or OB practices that appear to have multiple CAH patients and having our sales team go in there and follow up, that creates the mechanism or the feedback loop that allows us to understand where these patients are and the best way to educate, motivate and activate these patients.

因此，我認為，展望未來，從數據中挖掘出這一點非常重要。而且我認為，正如我之前提到的，能夠識別出那些似乎有很多 CAH 患者的初級保健或婦產科診所，並讓我們的銷售團隊去那裡進行跟進，這就能建立起一種機製或反饋迴路，使我們能夠了解這些患者在哪裡，以及如何最好地教育、激勵和調動這些患者。

Marc Goodman, Leerink Partners.

馬克古德曼，Leerink Partners。

Matt, just a clarification. You mentioned negative 4% price thoughts for 2026. Is that off the $5,500 that was, I think, previously guided for the full year of '25?

馬特，我只是想澄清一下。您提到了對 2026 年價格下跌 4% 的看法。這是從之前預測的 2025 年全年目標價 5500 美元中扣除的嗎？

And then I just actually have another follow-on on the conversation about ACTH antagonist and just how you guys view that drug to be used eventually if it ever comes out with everyone hopefully on CRENESSITY by then? Like is it an add-on? Do you think it will be a competitive product? Or how do you even view it at that point?

然後，我其實還有個後續問題，是關於ACTH拮抗劑的，以及你們如何看待這種藥物最終的應用，如果它真的上市的話，希望到那時大家都能用上CRENESSITY？它是附加元件嗎？你認為它會成為一款有競爭力的產品嗎？或者，到了那個時候，你又該如何看待這件事？

We haven't disclosed what the net price was for 2025, but you can think about the 4% being year-on-year, more heavily concentrated year-on-year in the first half of this year based upon the timing of when we entered into contracting.

我們尚未揭露 2025 年的淨價，但您可以認為 4% 是同比漲幅，而且由於我們簽訂合約的時間，同比漲幅在今年上半年更為集中。

But importantly, and Kyle mentioned this earlier, is that exiting 2025, our net revenue per script is going to be very similar throughout all of 2026. So we did take a bit of price through 2025, but do expect a lot of stability on the net price side as well as and most importantly, on the access side to continue to allow us to build this market.

但重要的是，正如凱爾之前提到的，到 2025 年結束時，我們每個劇本的淨收入在整個 2026 年都將非常相似。因此，我們預計到 2025 年價格會略有上漲，但預計淨價格方面以及最重要的准入方面都會保持穩定，從而使我們能夠繼續發展這個市場。

And then Marc, on your competitor question, I've learned a lot over the course of my first full year as CEO, and one of them is how to talk about competition. When it comes to CRENESSITY, we're really talking about two different programs, two different medicines at two different states. CRENESSITY is an approved medicine. It's had a great launch, and we have a multiple year head start. I think we've got a medicine that's changing the standard of care across the efficacy, the safety, tolerability, the formulations, and we're generating a lot of data over time.

馬克，關於你提到的競爭對手問題，在我擔任執行長的第一年裡，我學到了很多東西，其中之一就是如何談論競爭。說到 CRENESSITY，我們實際上是在談論兩個不同的項目、兩種不同的藥物，分別在兩個不同的州進行。CRENESSITY 是一種核准的藥物。它上市非常成功，我們擁有多年的領先優勢。我認為我們開發的這種藥物正在改變治療標準，它在療效、安全性、耐受性、製劑等方面都取得了進步，而且隨著時間的推移，我們正在累積大量數據。

I think it leaves us in a really good position. And I think that you all listening on the phone, certainly, I've been doing that here, looking at orphan drug launches, I'm really hard-pressed to see any medicine that delivers on the profile of CRENESSITY and is displaced at all by any future medicine. So I'm really excited about what we have with CRENESSITY. It's a two variable positive year for us. We've got a great medicine and a great team that's out there doing great things with prescribers and patients that are there, and we're going to focus on building this brand into a great medicine for patients in the company.

我認為這讓我們處於非常有利的地位。我想，所有正在電話裡收聽的各位，當然，我也一直在關注孤兒藥的上市情況，我真的很難看到有哪一種藥能達到 CRENESSITY 的效果，並且會被未來的任何藥物所取代。所以我對我們與 CRENESSITY 的合作感到非常興奮。對我們來說，今年是雙喜臨門的一年。我們擁有優秀的藥物和優秀的團隊，他們與處方醫生和患者一起做了很多了不起的事情，我們將專注於把這個品牌打造成為公司患者的優秀藥物。

Akash Tewari, Jefferies.

阿卡什‧特瓦里，傑富瑞集團。

Hi, this Phoebe on for Akash. My question is on CRENESSITY as well, but more so on the pipeline. We saw that there's a Phase 2 study being initiated for patients under four years old, which we know is not currently on the label. Can you talk about kind of the importance of the study and when we should expect an update here?

大家好，我是 Phoebe，替 Akash 寄來的。我的問題也與 CRENESSITY 有關，但更多的是關於管道方面。我們看到，針對四歲以下患者的二期研究正在啟動，而我們知道，該藥物目前並未在標籤上註明適用人群。您能談談這項研究的重要性以及我們何時能得到最新進展嗎？

And could we expect this to be sort of a growth opportunity when and if on market for this population?

如果這款產品面向該族群上市，我們是否可以期待它能帶來某種成長機會？

Yes. So as indicated, we are soon initiating 2032, which is a pediatric study. These are individuals less than four years of age, the youngest age being three months. And the intent is to expand our label, which currently is four years and above. So again, we're excited about this opportunity. We should have some data next year on that study.

是的。如同先前所提到的，我們即將啟動 2032 年的兒科研究。這些兒童年齡均小於四歲，最小的只有三個月大。我們的目標是擴大我們的標籤範圍，目前我們的標籤涵蓋四歲及以上兒童。所以，我們對這個機會感到非常興奮。明年我們應該可以得到這項研究的一些數據。

Sumant Kulkarni, Canaccord.

Sumant Kulkarni，Canaccord。

Good afternoon. Thanks for taking our questions. Bigger picture one here. It looks like you sold your UK and European rare commercial business recently. What does this mean for your plans to develop crinecerfont in UK and the rest of Europe? And does that decision mean Neurocrine is going to remain US focused? And how much did the potential enforcement of most favored nations pricing have to do that decision?

午安.謝謝您回答我們的問題。這裡要從更宏觀的角度來看這個問題。看來你最近出售了你在英國和歐洲的稀有商品商業業務。這對您在英國和歐洲其他地區開發 Crinecerfont 的計劃意味著什麼？這項決定是否意味著Neurocrine將繼續專注於美國市場？而最惠國定價的潛在執行情況對此決定產生了多大影響？

Yes. This is Kyle. I appreciate the question. I think when it comes to the EU business, the programs that we're working on over there weren't necessarily a good alignment for what we have for our own portfolio today. So we found a good place for those programs to go with the new team there.

是的。這是凱爾。感謝您的提問。我認為就歐盟業務而言，我們在那裡開展的專案並不一定與我們目前的業務組合相符。所以我們為這些項目找到了一個合適的歸宿，讓它們和新團隊一起發展。

In terms of our own interest, obviously, we're focusing on the US market now and making sure that we have a really good launch here with CRENESSITY and so far, so good there, and we want to keep focusing our attention there. And look at ways we can potentially bring CRENESSITY and other future medicines to Europe. Right now, we're not really looking at considerations and variables that play in most favored nation per se as much as we are focusing on the US market. But it is an area that is evolving. And before we make any decisions definitively outside the US, we'll want to get clarity on where that's going here in terms of a policy standpoint.

就我們自身的利益而言，顯然，我們現在專注於美國市場，確保 CRENESSITY 在這裡能夠順利上市，到目前為止，一切進展順利，我們希望繼續將注意力集中在那裡。並探討我們如何將 CRENESSITY 和其他未來藥物引入歐洲。目前，我們並沒有太多關注最惠國待遇本身所涉及的因素和變量，而是將重點放在了美國市場。但這是一個不斷發展的領域。在我們最終決定美國以外的任何事項之前，我們希望先弄清楚從政策角度來看，這些決定將走向何方。

Sean Laaman, Morgan Stanley.

肖恩拉曼，摩根士丹利。

Hi, Kyle and team, hope everyone's well, and thanks for taking my question. I have a pipeline question on 890. Just going back to the recent data you showed for INGREZZA and the 80% receptor occupancy, it seems like a pretty high hurdle. So do you think you can beat that with 890? Or is it really with 890 more about just expanding the population base through that long-acting profile?

嗨，Kyle和團隊，希望大家都好，感謝你們回答我的問題。我有一個關於890管道的問題。回顧您最近展示的 INGREZZA 的數據以及 80% 的受體佔有率，這似乎是一個相當高的門檻。所以你認為你能用 890 打敗它嗎？或者說，890 的真正意義在於透過其長效特性來擴大人口基礎？

Yes. Really good question because with INGREZZA, as you mentioned, we're actually doing really well from a receptor occupancy point of view. So with respect to 890, we're expecting at least the same receptor occupancy. But to your point, the potential for long-acting injectable formulations, that's because of reduced clearance and also reduced aqueous solubility.

是的。這是一個很好的問題，因為正如您所提到的，從受體佔有率的角度來看，INGREZZA 實際上做得非常好。因此，對於 890 而言，我們預計至少會具有相同的受體佔有率。但正如您所說，長效注射劑的潛力在於其清除率降低和水溶性降低。

So it's a molecule that really is designed to be both oral but administered relatively infrequently. And we think that could capture patients who are not doing so well or not so compliant on their current treatment.

所以，這種分子的設計初衷是既可以口服，又可以相對少頻率地給藥。我們認為這可以發現那些治療效果不佳或對目前治療依從性較差的患者。

Yes. Just to add to that, we've certainly looked at that potential with INGREZZA over time, and it's not a well-suited molecule for that as well as other follow-on molecules that we've had over time. So we're quite excited what we have with 890 and 675. Those are the next-generation VMAT2 inhibitors.

是的。補充一點，我們當然也研究過 INGREZZA 的這種潛力，但它並不是一個適合這種用途的分子，不如我們後來研發的其他後續分子。所以我們對890和675這兩款產品感到非常興奮。這些是新一代VMAT2抑制劑。

And it's taken us a while to get a molecule that actually has a profile that we think is competitive or if not better than INGREZZA. So, we're excited about getting this Phase 2 study up and running and looking to have data sometime towards the end of next year.

我們花了很長時間才找到一種分子，它的性質我們認為與 INGREZZA 相比具有競爭力，甚至更好。因此，我們很高興能夠啟動並進行這項二期研究，並希望在明年年底前獲得數據。

Danielle Brill, Truist.

Danielle Brill，Truist。

Hi guys, good afternoon. Thanks so much for the question. So I know we talked a lot about general barriers to prescribing CRENESSITY and mentioned a few times that two-third of your prescribers have written a single prescription. I guess I'm just trying to understand what's driving that pattern specifically.

大家好，下午好。非常感謝你的提問。我知道我們討論了很多關於開立 CRENESSITY 處方的普遍障礙，並且多次提到三分之二的處方醫生只開過一次處方。我只是想弄清楚究竟是什麼因素導致了這種模式。

Like how many CAH patients do these physicians typically manage? What feedback are you hearing regarding barriers or hesitations to expand adoption more broadly for these specific prescribers, patient bases at this point? Thank you.

這些醫生通常會管理多少先天性腎上腺皮質增生症（CAH）患者？目前，您聽到的關於在這些特定處方醫生和患者群體中更廣泛地推廣應用所面臨的障礙或猶豫的反饋有哪些？謝謝。

Yes. I think the circumstances are going to be different from physician to physician. But generally speaking, I think the two biggest factors here that are guiding the pace of adoption, especially with those that have written one prescription is really just the flow of patients into the practice. As I mentioned earlier, a lot of these community endocrinologists that are treating adult patients, they may only see their patient once a year. So that is a factor.

是的。我認為不同醫生的具體情況會有所不同。但總的來說，我認為影響普及速度的兩個最大因素，尤其是對於已經開過一張處方的人來說，實際上就是病患就診量。正如我之前提到的，許多治療成年患者的社區內分泌科醫生，可能一年只能見到他們的病人一次。所以這是一個因素。

And then the second one is, and this is not unique to CRENESSITY. A lot of these physicians also when they start a patient, they want to see how it does and get some clinical experience. A few months into treatment typically is when they would be starting the GC tapering. And anecdotally, what I'm hearing is that many of them are taking it easy in terms of just slowly bringing down the GC doses. So it's not sort of a forced down titration.

其次，第二個問題是，這並非 CRENESSITY 獨有的問題。許多醫師在開始治療病人時，也想看看治療效果如何，並累積一些臨床經驗。通常情況下，治療幾個月後就會開始逐漸減少糖皮質激素的劑量。據我所知，很多人在逐漸減少 GC 劑量方面都比較謹慎。所以這並不是一種強制遞減滴定。

So I think those two factors together kind of get at what might be inhibiting some of these doctors from getting their second or their third patient on treatment. But like I mentioned earlier, most community, adult endocrinologists, if they have classic CAH in their practice, only have a few patients. So this is a market that is -- has a small number of what I'd call KOLs or experts and then a large number out in the community that have very few patients. And so it's an inch deep and a mile wide, so to speak.

所以我認為這兩個因素加在一起，可能就解釋了為什麼有些醫生無法讓第二位或第三位患者接受治療。但正如我之前提到的，大多數社區成人內分泌科醫生，如果他們的診療實踐中有典型的先天性腎上腺皮質增生症（CAH）患者，也只有少數幾例。所以這是一個市場，其中有少數我稱之為 KOL 或專家的人，而社區裡有大量的人，但他們的患者卻很少。所以，可以說它深一英寸，寬一英里。

But in order for us to really optimize this opportunity, we have to reach and educate everyone, and that's what we're doing. And obviously, we're very pleased with the first year, and we expect to have a lot of success in 2026 and beyond.

但為了真正充分利用這個機會，我們必須接觸並教育所有人，而這正是我們正在做的。顯然，我們對第一年的成績非常滿意，並期待在 2026 年及以後取得更大的成功。

Thank you. That does end the Q&A session for today's call. I would now like to hand the call back to Kyle for any additional or closing remarks.

謝謝。今天的電話會議問答環節到此結束。現在我想把電話交還給凱爾，讓他補充或作總結發言。

Thanks, Clay. I want to thank you all for joining today and for the constructive discussion. During the call, we shared updates on our commercial performance and development programs as well as the outlook for the business.

謝謝你，克萊。感謝各位今天蒞臨並參與建設性討論。在電話會議中，我們分享了有關商業業績和發展計劃的最新信息，以及公司業務前景。

I want to be clear, our focus remains on disciplined execution as we think about 2026, which means a couple of things: driving revenue growth and diversification with INGREZZA and CRENESSITY, advancing the pipeline and the process of delivering meaningful -- and in this process, delivering meaningful long-term value for patients and shareholders. We've got a lot of momentum that we're building this year for a data-rich 2027. That's just going to be the tip of the iceberg. The way that the pipeline is set up will deliver a constant flow of data starting from '27 and in future years.

我想明確一點，展望 2026 年，我們的重點仍然是嚴謹的執行，這意味著兩件事：透過 INGREZZA 和 CRENESSITY 推動收入成長和多元化，推進產品線和交付有意義的成果的過程——在這個過程中，為患者和股東創造有意義的長期價值。今年我們累積了很大的勢頭，為2027年數據豐富的時代做好準備。那隻是冰山一角。該管道的設置方式將從 2027 年開始以及未來幾年持續提供資料流。

So in close, please don't hesitate to reach out on any of the topics that we discussed today. We look forward to continuing the dialogue and meeting with many of you as we progress throughout the year. So thanks again and talk to you soon.

最後，如果您對我們今天討論的任何話題有任何疑問，請隨時與我們聯繫。我們期待在今年的工作中繼續與各位對話並會面。再次感謝，期待下次再聊。

Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.

謝謝。今天的會議到此結束。感謝您抽空參與。您現在可以斷開連線了。