Neurocrine Biosciences Inc (NBIX) 2024 Q3 法說會逐字稿

Please stand by your program is about to begin.

請稍候，您的節目即將開始。

Good day, everyone and welcome to Neurocrine Biosciences’ reports third quarter results. (Operator Instructions)

大家好，歡迎來到 Neurocrine Biosciences 報告第三季業績。（操作員說明）

Please note that this call will be recorded and I will be standing by should you need any assistance.

請注意，此通話將被錄音，如果您需要任何協助，我將隨時待命。

It is now my pleasure to turn today’s call over to Todd Tushla, Vice President of Investor Relations. Please go ahead.

現在，我很高興將今天的電話轉給投資者關係副總裁 Todd Tushla。請繼續。

Thank you, and happy Halloween eve. Welcome to Neurocrine Biosciences’ third quarter 2024 earnings call. With me are Kyle Gano, our Chief Executive Officer; Matt Abernethy, Chief Financial Officer; Eric Benevich, Chief Commercial Officer; and Eiry Roberts, Chief Medical Officer.

謝謝你，萬聖節快樂。歡迎參加 Neurocrine Biosciences 2024 年第三季財報電話會議。與我在一起的有我們的執行長凱爾·加諾 (Kyle Gano)；馬特‧阿伯內西，財務長；貝內維奇 (Eric Benevich)，商務長；和首席醫療官艾里·羅伯茨（Eiry Roberts）。

Note that today, 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.

請注意，今天我們將做出前瞻性陳述。這些陳述存在一定的風險和不確定性，我們的實際結果可能有重大差異。我鼓勵您查看我們最新的 SEC 文件中討論的風險因素。

With that, for the first time, I hand it over to Kyle.

就這樣，我第一次把它交給凱爾。

Thank you, Todd. Before we dive in, I'd like to acknowledge that this is my first earnings call as Neurocrine’s CEO. I'm excited to share my enthusiasm for our future, so my opening remarks may run a bit longer than usual.

謝謝你，托德。在我們深入討論之前，我想承認這是我作為 Neurocrine 執行長的第一次財報電話會議。我很高興能與大家分享我對未來的熱情，因此我的開場白可能比平常要長一些。

First, I want to express my deep gratitude to our Board of Directors for their confidence in my leadership as we embark on this next chapter of growth. Thanks to the exceptional guidance of our past CEOs, Gary Lyons and Kevin Gorman, Neurocrine is in a strong position to become a true leader in neuroscience. I extend my heartfelt thanks to both Gary, Kevin for their invaluable contributions to the company's success.

首先，我要向董事會表達深深的感謝，感謝他們在我們開啟下一個成長篇章時對我的領導能力的信任。由於我們前任執行長加里·里昂斯 (Gary Lyons) 和凱文·戈爾曼 (Kevin Gorman) 的卓越指導，Neurocrine 處於成為神經科學領域真正領導者的有利地位。我衷心感謝加里和凱文為公司的成功做出的寶貴貢獻。

Given our company's growing multibillion-dollar franchise in INGREZZA, the potential of Crinecerfont as our next blockbuster, the registrational programs for NBI-’845 and NBI-’568, and what we believe to be the industry's most robust neuroscience-focused pipeline, Neurocrine’s future is bright with significant value creation ahead.

鑑於我們公司在INGREZZA 中不斷增長的數十億美元的特許經營權、Crinecerfont 作為我們下一個重磅炸彈的潛力、NBI-845 和NBI-568 的註冊計劃，以及我們認為是業界最強大的神經科學 - Neurocrine 的未來是光明的，未來將創造巨大的價值。

Built on this, at our core, we are a company driven by innovation and operational excellence. Our capital allocation strategy reflects this by prioritizing revenue growth, diversification, and regenerative pipeline. As announced in this morning's press release, our Board of Directors has authorized a share repurchase plan of $300 million, which we intend to implement through an accelerated share repurchase transaction.

以此為基礎，我們是一家以創新和卓越營運為驅動力的公司。我們的資本配置策略透過優先考慮收入成長、多元化和再生管道來反映這一點。正如今天上午的新聞稿中宣布的那樣，我們的董事會已批准一項 3 億美元的股票回購計劃，我們打算透過加速股票回購交易來實施該計劃。

Considering our expected revenue growth for both INGREZZA and Crinecerfont and the breadth of the early to late-stage pipeline, we believe Neurocrine is trading at a significant discount to its underlying enterprise valuation, making share repurchase a high return investment opportunity. In addition, we maintain the flexibility to further invest in the growth of our business.

考慮到我們對 INGREZZA 和 Crinecerfont 的預期收入增長以及早期到後期管道的廣度，我們認為 Neurocrine 的交易價格與其基礎企業估值相比有很大折扣，這使得股票回購成為高回報的投資機會。此外，我們保持進一步投資於業務成長的靈活性。

On the topic of capital allocation, our strategy is aligned with our plan for value creation. This approach is driven by four key pillars that ensure we continue as a high-growth company and position ourselves as a leading neuroscience organization with both commercial and scientific scale and expertise.

在資本配置方面，我們的策略與我們的價值創造計畫是一致的。這種方法由四個關鍵支柱驅動，確保我們繼續作為一家高成長的公司，並將自己定位為具有商業和科學規模和專業知識的領先神經科學組織。

The four pillars of our strategic plan are: one, drive revenue growth by investing in INGREZZA and preparing for a successful Crinecerfont launch. Two, aggressively develop our highest value pipeline assets, such as NBI-’845 and NBI-’568, by accelerating early-stage programs to proof-of-concept. Three, pursue external opportunities to expand our portfolio with strategically aligned assets that can be rapidly developed into commercial products, leveraging our expertise in neurology, psychiatry, endocrinology, and our R&D to commercial infrastructure. And four, return excess capital to shareholders beyond what is required for organic and inorganic growth. With these guiding pillars, we are well positioned to deliver substantial near and long-term value to both patients and shareholders.

我們策略計畫的四大支柱是：第一，透過投資 INGREZZA 並為成功推出 Crinecerfont 做準備來推動營收成長。第二，透過加速早期專案的概念驗證，積極開發我們最高價值的管道資產，例如 NBI-845 和 NBI-568。第三，尋求外部機會，利用我們在神經病學、精神病學、內分泌學方面的專業知識以及我們對商業基礎設施的研發，利用戰略上一致的資產來擴大我們的投資組合，這些資產可以快速開發成商業產品。第四，將超出有機和無機成長所需的多餘資本返還給股東。有了這些指導支柱，我們就能夠為病患和股東提供可觀的近期和長期價值。

Now as far as Q3 with INGREZZA, we continue to reach more and more patients suffering from Tardive Dyskinesia and Huntington’s Disease Chorea. With an estimated 85% of the 800,000 patients with Tardive Dyskinesia not yet receiving a VMAT2 inhibitor for the symptoms, there is much work and opportunity ahead. To this end, we are again raising full year in INGREZZA guidance.

現在，就 INGREZZA 的第三季而言，我們繼續接觸到越來越多患有遲發性運動障礙和亨廷頓舞蹈症的患者。據估計，在 80 萬名遲發性運動障礙患者中，有 85% 尚未接受 VMAT2 抑制劑治療，因此未來還有很多工作和機會。為此，我們再次上調全年 INGREZZA 指引。

Regarding Crinecerfont, our regulatory activities remain on track with potential approvals by year-end. We're excited to deliver a groundbreaking treatment to patients who have lacked a new option for 70 years. Like INGREZZA, Crinecerfont, when approved, will be a first-in-class medicine for patients and has the same hallmarks of a blockbuster medicine. No doubt, Crinecerfont will offer a second leg of revenue growth for Neurocrine and help diversify our business over time.

關於 Crinecerfont，我們的監管活動仍在按計劃進行，年底前可能會獲得批准。我們很高興能為 70 年來一直缺乏新選擇的患者提供突破性的治療方法。與 INGREZZA 一樣，Crinecerfont 一旦獲得批准，將成為患者的一流藥物，並具有與重磅藥物相同的特徵。毫無疑問，Crinecerfont 將為 Neurocrine 提供第二個收入成長點，並幫助我們隨著時間的推移實現業務多元化。

On the pipeline front, this year we obtained proof-of-concept data in two of our three novel psychiatry Phase II programs. Having spent nearly 25 years in this therapeutic area, I understand inherent risk that comes with drug development within psychiatry. Achieving success in just one of these programs would have been remarkable. Succeeding in two out of three exceeded our internal expectations and significantly de-risked both assets and their associated biology.

在管道方面，今年我們在三個新穎的精神病學二期項目中的兩個項目中獲得了概念驗證數據。我在這治療領域工作了近 25 年，了解精神科藥物開發所帶來的固有風險。如果其中一個專案取得成功就已經是了不起的事情了。三分之二的成功超出了我們的內部預期，並顯著降低了資產及其相關生物學的風險。

As we move NBI-’845, our AMPA- positive allosteric modulators for major depressive disorder, and NBI-’568, our selective M4 muscarinic agonist for schizophrenia, into registrational studies, early next year, we are well positioned for the next key value drivers after INGREZZA and Crinecerfont.

當我們將NBI-845（用於治療重度憂鬱症的AMPA 陽性變構調節劑）和NBI-568（用於治療精神分裂症的選擇性M4 毒蕈鹼激動劑）納入註冊研究時，明年初，我們已做好充分準備：繼 INGREZZA 和 Crinecerfont 之後的下一個關鍵價值驅動因素。

With several internally developed molecules set to enter clinical trials and multiple Phase III programs lined up for 2025, prioritizing R&D investment becomes even more critical. Today's decision to deprioritize Luvadaxistat in NBI-’104 reflects this disciplined approach. Decisions like these are never easy, and I want to acknowledge and thank the patients, families, and healthcare professionals involved in the studies.

隨著多個內部開發的分子即將進入臨床試驗，以及多個 III 期計畫將於 2025 年排隊，優先考慮研發投資變得更加重要。今天在 NBI-104 中取消 Luvadaxistat 的優先順序的決定反映了這種嚴格的方法。做出這樣的決定絕非易事，我要感謝參與這些研究的病人、家屬和醫療保健專業人員。

Pipeline discipline and capital allocation are cornerstones of our strategy, and we will continue to evaluate all of our clinical and preclinical programs to ensure we invest in potential treatments that offer meaningful value for patients and shareholders alike.

管道紀律和資本配置是我們策略的基石，我們將繼續評估我們所有的臨床和臨床前項目，以確保我們投資於為患者和股東提供有意義價值的潛在治療方法。

In closing, with an exceptional leadership team and a dedicated, energized organization, we are well positioned to become the leading neuroscience company. I'd like to wrap up my remarks by sharing thoughts I expressed earlier this year when Kevin announced his retirement. I'm inspired by the work we have ahead, more confident than ever in the potential of our future, and immeasurably proud to collaborate with the best team in the industry to relieve suffering for people with great needs but few options and drive value for our shareholders.

最後，憑藉著卓越的領導團隊和敬業、充滿活力的組織，我們完全有能力成為領先的神經科學公司。我想透過分享今年早些時候凱文宣布退休時表達的想法來結束我的發言。我對我們未來的工作感到鼓舞，對我們未來的潛力比以往任何時候都更有信心，並且非常自豪能夠與業內最好的團隊合作，為有巨大需求但選擇很少的人們減輕痛苦，並為我們的公司創造價值。

With that, I'll now turn it over to Matt.

有了這個，我現在將把它交給馬特。

Thank you, Kyle. Our INGREZZA team delivered $613 million in Q3 sales, reflecting continued strong patient demand and positioning us to increase our guidance range to $2.3 to $2.32 billion, reflecting 25% year-over-year growth at the midpoint of this range.

謝謝你，凱爾。我們的INGREZZA 團隊在第三季度實現了6.13 億美元的銷售額，反映了持續強勁的患者需求，並使我們將指導範圍提高到2.3 至23.2 億美元，反映出該範圍中點的同比增長25% 。

The Tardive Dyskinesia market remains very attractive, and as Kyle mentioned, our number one capital allocation priority remains investing in INGREZZA. Of note, our psychiatry and long-term care salesforce expansion is complete, and fully expect to see the benefit of this expansion during the first half of next year.

遲發性運動障礙市場仍然非常有吸引力，正如凱爾所提到的，我們的第一個資本配置優先事項仍然是投資 INGREZZA。值得注意的是，我們的精神科和長期照護銷售團隊擴張已經完成，並完全期望在明年上半年看到這種擴張的好處。

In addition, our Crinecerfont commercial and field medical teams continue to build market awareness of Congenital Adrenal Hyperplasia and gain disease state insight in preparation for the PDUFA dates in late December. INGREZZA and Crinecerfont growth over the years ahead will provide Neurocrine the resources to invest in our growing pipeline.

此外，我們的 Crinecerfont 商業和現場醫療團隊繼續提高先天性腎上腺增生症的市場意識，並深入了解疾病狀態，為 12 月底的 PDUFA 日期做準備。INGREZZA 和 Crinecerfont 未來幾年的成長將為 Neurocrine 提供投資於我們不斷成長的產品線的資源。

On the R&D side, the teams are busy preparing for the initiation of two major Phase III programs in major depressive disorder and schizophrenia. Although we're still working through our budget process for 2025, you should expect an overall increase in both dollars and percentage of revenue allocated to R&D, likely to be in the low-to-mid 30% range of revenue next year.

在研發方面，團隊正忙於準備啟動針對重度憂鬱症和精神分裂症的兩個主要三期計畫。儘管我們仍在製定 2025 年的預算流程，但您應該預期分配給研發的美元和收入百分比都會整體增加，明年可能會達到收入的 30% 中低範圍。

We will be meeting with the agency over the coming months on both the NBI-’845 and NBI-’568 programs and will provide further insight into R&D investment expectations for 2025 during our Q4 earnings call in early February.

我們將在未來幾個月與該機構就 NBI-845 和 NBI-568 計劃舉行會議，並將在 2 月初的第四季度財報電話會議上進一步深入了解 2025 年的研發投資預期。

Returning to 2024, we have made significant progress in growing our revenue to over $2 billion and advancing and expanding our pipeline. We anticipate that 2025 will be a year focused on investment for continued growth into the future, which we believe will drive long-term shareholder value.

回顧 2024 年，我們在營收成長至超過 20 億美元以及推動和擴大產品線方面取得了重大進展。我們預計 2025 年將是專注於未來持續成長投資的一年，我們相信這將推動長期股東價值。

As highlighted in our press release, our board has approved a $300 million share repurchase plan. In the coming days, we intend to enter into a $300 million accelerated share repurchase transaction, subject to market conditions. Together with our board, we believe recent share price levels reflect neither the current value of the company today, nor the growth prospects we expect to achieve in the future. As a result, we believe this use of capital will benefit our shareholders while also preserving financial flexibility to make the investments required to continue the advancement of our leading neuroscience company.

正如我們的新聞稿中所強調的，我們的董事會已批准一項 3 億美元的股票回購計畫。未來幾天，我們打算根據市場狀況進行 3 億美元的加速股票回購交易。我們與董事會一起認為，最近的股價水準既不能反映公司當前的價值，也不能反映我們未來預期實現的成長前景。因此，我們相信這種資本的使用將使我們的股東受益，同時也能保持財務靈活性，以便進行繼續發展我們領先的神經科學公司所需的投資。

With that, I'll now hand the call over to our Chief Commercial Officer, Eric Benevich, to provide an update on INGREZZA and also our CAH launch preparations. Eric?

現在，我將把電話轉交給我們的首席商務官 Eric Benevich，以提供有關 INGREZZA 的最新資訊以及我們的 CAH 啟動準備。艾瑞克？

Thanks, Matt. We again delivered a strong quarter for INGREZZA with over 26% year-over-year growth driven primarily by demand and continued patient appliance across the Tardive Dyskinesia and Huntington's disease Chorea indications. INGREZZA sales are now annualizing at over $2.4 billion, and with 14 more years of exclusivity ahead of us, we still have a tremendous opportunity to help even more patients.

謝謝，馬特。我們再次為 INGREZZA 帶來了強勁的季度業績，年成長超過 26%，這主要是由需求以及遲發性運動障礙和亨廷頓舞蹈症適應症的患者持續使用所推動的。INGREZZA 目前的年銷售額超過 24 億美元，我們還有 14 年的獨家經營權，我們仍然有巨大的機會來幫助更多患者。

It's been a number of years since we last updated our TD prevalence estimates. After conducting a thorough literature review and analyzing claims data for antipsychotic utilization, we're now estimating TD prevalence of at least 800,000 individuals in the US. Given the continually increasing utilization of dopamine-blocking antipsychotics, the size of the TD population continues to grow, and we continue our efforts to educate and help healthcare providers identify appropriate treatment candidates for INGREZZA.

距離我們上次更新 TD 盛行率估計值已經有很多年了。在進行徹底的文獻回顧並分析抗精神病藥物使用的索賠數據後，我們現在估計美國至少 80 萬人的 TD 盛行率。鑑於多巴胺阻斷抗精神病藥物的使用不斷增加，TD 族群規模持續成長，我們將繼續努力教育和幫助醫療保健提供者確定 INGREZZA 的合適治療候選者。

Earlier this year, we made the decision to expand our INGREZZA salesforce. This expansion is really a reflection of two things, the remaining significant growth potential in the TD market with only a third or less of TD patients currently diagnosed, and the substantially increased number of TD treaters developed over the last few years, especially in the psychiatry segment. We made the decision to expand our field teams in a manner consistent with the market dynamics and commensurate with the INGREZZA franchise opportunity.

今年早些時候，我們決定擴大 INGREZZA 銷售隊伍。這種擴張實際上反映了兩件事，即TD 市場剩餘的巨大成長潛力，目前只有三分之一或更少的TD 患者得到診斷，以及過去幾年開發的TD 治療者數量大幅增加，特別是在精神病學領域部分。我們決定以符合市場動態並與 INGREZZA 特許經營機會相稱的方式擴大我們的現場團隊。

On that note, I'm pleased to report that the psychiatry and long-term care salesforce expansions are now complete. Our newest team members are now in the field and settling into their roles. As noted on our Q2 earnings call, based upon our previous experience, it'll take a couple of quarters to see the full impact from this expansion on diagnosis and treatment rates.

在這一點上，我很高興地報告，精神病學和長期護理銷售團隊的擴張現已完成。我們最新的團隊成員現已在現場並適應他們的角色。正如我們在第二季財報電話會議上指出的那樣，根據我們先前的經驗，需要幾個季度的時間才能看到這種擴張對診斷和治療率的全面影響。

Turning to Crinecerfont, our rare disease endocrinology team remains focused on providing congenital adrenal hyperplasia, or CAH disease state education to the endocrinology healthcare providers and patient communities. Our team is eager and ready to immediately begin working with the CAH community should Crinecerfont be approved by the FDA, year-end.

轉向 Crinecerfont，我們的罕見疾病內分泌團隊仍然專注於為內分泌醫療保健提供者和患者社區提供先天性腎上腺增生或 CAH 疾病狀態教育。如果 Crinecerfont 年底獲得 FDA 批准，我們的團隊渴望並準備好立即開始與 CAH 社群合作。

I know many investors are contemplating the Crinecerfont launch dynamics. While Crinecerfont has all the characteristics of a future blockbuster, it won't happen overnight. We're building a foundation with our disease state educational efforts during the pre-launch period. And assuming approval, we'll be in a good position to launch quickly.

我知道許多投資者正在考慮 Crinecerfont 的推出動態。雖然 Crinecerfont 具備未來熱門產品的所有特徵，但它不會一蹴可幾。我們正在為啟動前的疾病狀態教育工作奠定基礎。如果獲得批准，我們將能夠快速啟動。

We intend to offer a free goods program during the period when patients' insurance reimbursement claims are being adjudicated and to enable endocrinologists to get familiar with the benefit-risk profile of Crinecerfont. And while payer interactions to-date have been positive, as with most newly launched products, commercial payers typically have new-to-market coverage restrictions or even policies to block reimbursement for up to the first six months when a product is launched.

我們打算在病患保險報銷索賠審理期間提供免費商品計劃，以使內分泌科醫生熟悉 Crinecerfont 的利益風險概況。儘管迄今為止與付款人的互動一直是積極的，但與大多數新推出的產品一樣，商業付款人通常會制定新上市的承保限制，甚至在產品推出後的前六個月內製定阻止報銷的政策。

With an estimated 60% to 70% of CAH patients under commercial coverage, this will mean delayed reimbursement for many patients in the first half of the year. But we're adept at managing such situations as seen with our experience managing the formulary exceptions process with INGREZZA. The goal is to help appropriate CAH patients get started on treatment while we work through their reimbursement.

估計有 60% 至 70% 的 CAH 患者享有商業保險，這將意味著許多患者在今年上半年的報銷將被推遲。但從我們與 INGREZZA 管理處方例外流程的經驗來看，我們擅長管理此類情況。我們的目標是幫助合適的 CAH 患者開始治療，同時我們處理他們的報銷。

All-in-all, the rare endocrinology team is super excited about the opportunity to help the CAH patient population who have not had a new treatment option in over 70 years.

總而言之，罕見的內分泌學團隊對於有機會幫助 70 多年來沒有新的治療選擇的 CAH 患者群體感到非常興奮。

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

因此，我會將電話轉給我的同事、我們的首席醫療官 Eiry Roberts 博士。

Thank you, Eric, and good morning, everyone. I'll begin today's clinical update with Crinecerfont. We continue to have constructive interactions with the FDA and remain on track for the December 29 and 30, PDUFA dates. Given the calendar and end-of-the-year timing, it would not be surprising to potentially receive approval for both formulations on December the 30, which falls on a Monday.

謝謝你，艾瑞克，大家早安。我將從 Crinecerfont 開始今天的臨床更新。我們繼續與 FDA 進行建設性互動，並繼續按計劃完成 12 月 29 日和 30 日的 PDUFA 日期。考慮到日曆和年終時間，這兩種方案在 12 月 30 日（週一）獲得批准也就不足為奇了。

Turning to the mid-stage pipeline, last month we disclosed that the ERUDITE study of luvadaxistat as a potential treatment for cognitive impairment associated with schizophrenia failed to meet its primary endpoint and thus did not replicate the positive findings on cognition previously reported in the INTERACT study.

談到中期管道，上個月我們披露，關於luvadaxistat 作為精神分裂症相關認知障礙的潛在治療方法的ERUDITE 研究未能達到其主要終點，因此沒有復制先前在INTERACT 研究中報告的認知方面的積極結果。

The results from the ERUDITE were confounded by variability in cognition measures across the population studied and the potential imbalance in baseline characteristics for enrolled subjects. As Kyle mentioned, we're therefore discontinuing this program together with the NBI-104 T-type calcium channel antagonist program in CSWS and focusing resources on advancing NBI-’845 and NBI-’568 into Phase III studies.

ERUDITE 的結果因研究族群認知測量的變異性以及登記受試者基線特徵的潛在不平衡而令人困惑。正如 Kyle 所提到的，因此我們將停止該項目以及 CSWS 中的 NBI-104 T 型鈣通道拮抗劑項目，並將資源集中於將 NBI-845 和 NBI-568 推進到 III 期研究。

Both NBI-’845, our AMPA positive allosteric modulator for the treatment of major depressive disorder, and NBI-’568, the selective M4 orthosteric agonist for the treatment of schizophrenia, continue to make good progress towards our end-of-Phase II interactions with the FDA, which we anticipate will occur over the next few months to enable the start of registrational studies for each of these programs in the first half of 2025.

NBI-845（用於治療重度憂鬱症的 AMPA 正變構調節劑）和 NBI-568（用於治療精神分裂症的選擇性 M4 正構激動劑）繼續在我們的臨床終點方面取得良好進展。與FDA 的第二階段互動，我們預計將在未來幾個月內進行，以便在2025 年上半年開始每個計畫的註冊研究。

We will provide more insight into study specifics over the coming months, together with our plans to publish key Phase II information from each of these programs in the latter part of 2025 once these registration studies are up and running.

我們將在未來幾個月內提供有關研究細節的更多見解，並計劃在這些註冊研究啟動並運行後於 2025 年下半年發布每個項目的關鍵 II 期資訊。

Shifting to NBI-’770, our NMDA NR2B NAM negative allosteric modulator for the treatment of major depressive disorder, the Phase II program for this molecule continues to enroll well with top-line data anticipated in 2025. The remainder of the pipeline is also progressing well, including the four muscarinic programs currently in Phase I development.

轉向 NBI-770（我們用於治療重度憂鬱症的 NMDA NR2B NAM 負變構調節劑），該分子的 II 期計畫繼續順利入組，預計將在 2025 年獲得頂線數據。管線的其餘部分也進展順利，包括目前處於第一階段開發的四個毒蕈鹼專案。

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

這樣，我會將電話轉回給凱爾。凱爾？

Thanks, Eiry. We're ready to take questions.

謝謝，艾里。我們準備好回答問題。

(Operator Instructions)

（操作員說明）

Chris Shibutani, Goldman Sachs.

克里斯·澀谷，高盛。

Thank you very much. Good morning. Congratulations on a clearly strong quarter commercially. I wanted to ask about going forward thinking about the pipeline, people as well as strategy. Eiry, we appreciate your comments. I think you have announced previously that you're looking to step away. Kyle, have you given thought to the point people who will be running the role that Eiry has been involved with as well as your previous role, which was really managing the business development leadership there, since I noticed quite a bit of focus on capital allocation.

非常感謝。早安.恭喜本季的商業表現明顯強勁。我想問關於未來的管道、人員和策略的思考。Eiry，我們感謝您的評論。我想你之前已經宣布過你打算離開。凱爾（Kyle），您是否考慮過將擔任埃里（Eiry）參與的角色以及您之前的角色（實際上是管理那裡的業務開發領導力）的人員，因為我注意到相當多的關注點是資本分配。

And secondly, can you just give us an update on the NextGen VMAT2 inhibitor? I know we started Phase I at the start of this year. But some visibility into when we could learn more would be great. Thank you.

其次，可以為我們介紹 NextGen VMAT2 抑制劑的最新情況嗎？我知道我們在今年年初開始了第一階段。但如果能了解我們何時可以了解更多那就太好了。謝謝。

Thanks, Chris. This is Kyle. I'll start, and then I'll have Eiry and the team, add anything that I missed here. For our VMAT2 follow-on compound, this is NBI-’890. What we're looking here to do is to have a more potent compound that would be amenable to all the same indications that we see advantages for INGREZZA, but also offer the opportunity to develop a long-acting injectable, which we know is important to the prescriber base as well as to patients. So stay tuned on that. The program is currently in Phase I. We'll look to move that into patients next year, pending the review of the ongoing Phase I data.

謝謝，克里斯。這是凱爾。我先開始，然後我會讓 Eiry 和團隊添加我在這裡錯過的任何內容。對於我們的 VMAT2 後續化合物，這是 NBI-890。我們在這裡尋找的是一種更有效的化合物，它可以適應我們認為 INGREZZA 優勢的所有相同跡象，但也提供了開髮長效注射劑的機會，我們知道這對於處方者基礎以及患者。所以請繼續關注。該計畫目前處於第一階段。

Yeah. Thank you.

是的。謝謝。

Paul Matteis, Stifel.

保羅馬蒂斯，斯蒂菲爾。

Thanks so much for taking my question. Kyle, congrats on moving to the CEO seat. I want to ask you a question just about BD and philosophically where you stand. You guys in your public commentary over the years have kind of ebbed and flowed to the degree to which you've talked about prioritizing smaller deals versus something larger in the $3 billion to $4 billion range. How do you think about capacity now, and strategically, do you feel like this is the right time for Neurocrine over the next year, year and a half to do something that's more meaningful and bolder for a later stage asset? Or do you still like this kind of smaller BD, spread the best strategy that you've employed so far? Thanks so much.

非常感謝您提出我的問題。凱爾，恭喜您晉升為執行長。我想問你一個關於 BD 的問題以及你在哲學上的立場。多年來，你們在公開評論中的言論有所起伏，以至於你們談到優先考慮較小的交易，而不是 30 億至 40 億美元範圍內的較大交易。您如何看待現在的產能，從策略上講，您是否認為現在是 Neurocrine 在未來一年、一年半的時間裡為後期資產做一些更有意義、更大膽的事情的合適時機？或者你還喜歡這種較小的BD，傳播你迄今為止所採用的最佳策略嗎？非常感謝。

Thanks, Paul. Appreciate the question. You know, in terms of our BD activities, the team that we have here continues to work with a high degree of urgency. Fortunately, we don't feel like we have to do something right now, either large or small. We've got a very deep and diversified portfolio with a number of investments that we're making that are late stage next year. And we've talked about some of those already with NBI-’845 and major depressive disorder and NBI-’568, our program in development with schizophrenia.

謝謝，保羅。感謝這個問題。您知道，就我們的業務拓展活動而言，我們的團隊繼續以高度緊迫的態度開展工作。幸運的是，我們覺得現在不需要做任何事情，無論是大事還是小事。我們擁有非常深入且多元化的投資組合，其中許多投資將於明年後期進行。我們已經討論了其中一些已經參與 NBI-845 和重度憂鬱症的項目，以及 NBI-568（我們正在開發的針對精神分裂症的項目）。

And behind that, we have a very rich early to mid-stage pipeline that's developing. So right now, my mind is learning about the landscape and figuring out what areas that we want to invest in moving forward, which assets are in those areas, but really focused on executing and what we have in the pipeline right now, making sure that we're doing whatever we can there to put those programs in the best possible situation for success.

在這背後，我們有一個非常豐富的早期到中期管道正在開發中。所以現在，我的想法是了解情況，並弄清楚我們想要投資哪些領域，哪些資產屬於這些領域，但真正專注於執行以及我們目前正在準備的內容，確保我們正在盡一切努力使這些計劃處於盡可能最好的狀態，以取得成功。

And if something comes out down the road that is a program, a technology that is something that we could utilize and takes advantage of our expertise and infrastructure, we'll look at that seriously. But right now, we feel like we're in a very enviable position.

如果未來出現一個項目、一項我們可以利用並利用我們的專業知識和基礎設施的技術，我們會認真考慮。但現在，我們感覺自己處於一個非常令人羨慕的位置。

Yeah, fortunately, our financial flexibility is very strong at the moment. A lot of cash, continued cash flow generation, a very clean balance sheet as we started our convertible debt earlier this year, as you're aware. So we do have financial flexibility into the future if we did decide that was something for us to do. And as Kyle said, a very enviable position to be in.

是的，幸運的是，我們目前的財務彈性非常強。如您所知，我們今年稍早開始發行可轉換債務，因此擁有大量現金、持續產生現金流、非常乾淨的資產負債表。因此，如果我們確實決定這是我們要做的事情，那麼我們未來確實擁有財務靈活性。正如凱爾所說，這是一個非常令人羨慕的位置。

Okay. Thanks, guys.

好的。謝謝，夥計們。

Thank you. David Ansellem, Piper Sandler.

謝謝。大衛安塞勒姆，派珀桑德勒。

Hey, thanks. So looking into ’25 and beyond, how are you thinking about the potential that you might need to compete more on price to hold INGREZZA share versus Austedo? And then as you think about IRA negotiations, do you anticipate any impact on INGREZZA pricing once Austedo is included in IRA negotiations? In other words, some sort of spillover effect, if you will. And then secondly, just on ’568, just remind us how you're thinking about indications beyond schizophrenia, say, the psychosis, for instance and/or are you looking at the other muscarinics for indications beyond schizophrenia? Just help us understand your thought process there. Thank you.

嘿，謝謝。因此，展望 25 年後及以後，您如何看待您可能需要在價格上進行更多競爭才能持有 INGREZZA 股份而不是 Austedo 的潛力？然後，當您考慮 IRA 談判時，您預計一旦 Austedo 被納入 IRA 談判，會對 INGREZZA 定價產生任何影響嗎？換句話說，如果你願意的話，可以說是某種溢出效應。其次，就在 568 上，提醒我們您如何考慮精神分裂症以外的適應症，例如精神病，和/或您是否正在考慮其他毒蕈鹼藥物以尋找精神分裂症以外的適應症？只需幫助我們了解您的思考過程即可。謝謝。

[And so] David, we're going to handle the first chunk of your questions. And just out of respect for others in queue, we'll leave the muscarinic question to others. But Eric can comment on price. The only real specifics we're going to give as it relates to 2025 on price is we do, sitting here today, expect our net revenue per script to be very similar to what we've seen in 2024, so no significant change that we can see at this time for 2025. But, Eric?

[所以]大衛，我們將處理你的第一個問題。出於對排隊中其他人的尊重，我們將把毒蕈鹼問題留給其他人。但埃里克可以評論價格。我們要給出的與 2025 年價格相關的唯一真正細節是，我們今天坐在這裡，預計每個腳本的淨收入將與我們在 2024 年看到的非常相似，因此我們不會做出重大改變。此時可以看到2025 年。但是，艾瑞克？

Yeah. So what I'll say is that every year we continue to assess our contracting strategies. And we invest in contracts where we think it makes sense. And in some cases, we have contracted access where we think that it's favorable. In other cases, we look at the contract and make decisions to pull back. And so as a result, the coverage landscape changes from year to year.

是的。所以我要說的是，每年我們都會繼續評估我們的承包策略。我們投資於我們認為有意義的合約。在某些情況下，我們會在我們認為有利的情況下簽訂合約。在其他情況下，我們會查看合約並決定撤回。因此，覆蓋範圍每年都會發生變化。

But overall, our access has and continues to remain excellent with over 80% of lives covered and the majority of patients paying $10 or less. And we expect that to continue into the future. The other thing that I'll say is that we're going to learn from the first few waves of drugs that go through the negotiation process in terms of what their access looks like vis-a-vis non-negotiated drugs.

但總體而言，我們的服務已經並將繼續保持良好狀態，覆蓋了超過 80% 的生命，大多數患者支付的費用為 10 美元或更少。我們預計這種情況將持續到未來。我要說的另一件事是，我們將從前幾波經過談判過程的藥物中學習，以了解它們相對於非談判藥物的獲取。

So stay tuned. But ultimately, our goal is to make sure that patients that need access to INGREZZA continue to have access. We're trying to do that in a manner that is responsible from a financial perspective.

所以請繼續關注。但最終，我們的目標是確保需要 INGREZZA 的患者能夠繼續獲得服務。從財務角度來看，我們正試圖以負責任的方式做到這一點。

Understood. Thank you.

明白了。謝謝。

Thank you.

謝謝。

Akash Tewari, Jeffrey.

阿卡什·特瓦里，傑弗裡。

Hi. Thank you for taking your question. This is Phoebe on for Akash. On your M1/M4 asset, can you talk about why you feel confident that you don't have to dose with Tropium like [CAH] datas? And then additionally, what should we expect to learn from initial Phase I human data next year for the muscarinic? Thank you.

你好。感謝您提出問題。這是阿卡什的菲比。關於您的 M1/M4 資產，您能否談談為什麼您有信心不必使用像 [CAH] 數據那樣的 Tropium？另外，我們應該從明年毒蕈鹼的初始第一階段人體數據中學到什麼？謝謝。

Good morning. Thanks for the question. On NBI-’570, it's a very interesting molecule in the sense that it's one of a basket of small molecules that we have in development that range from M1 to M4 selectivity across the muscarinics. And 570 has equal potency on M1 and M4. One of the things that's exciting about this molecule, as well as the suite of molecules, is that it relies on explicit selectivity of just M1 and M4 across the muscarinics, which we know are the subtypes M1 through M5. So we've got that going for us out of the gate.

早安.謝謝你的提問。在 NBI-570 上，它是一個非常有趣的分子，因為它是我們正在開發的一籃子小分子之一，對毒蕈鹼的選擇性範圍從 M1 到 M4。570 對 M1 和 M4 具有相同的效力。這個分子以及這組分子的令人興奮的事情之一是它依賴 M1 和 M4 對毒蕈鹼的顯式選擇性，我們知道毒蕈鹼是 M1 到 M5 的亞型。所以我們已經把這件事做好了。

But the other piece that Sosei Heptares, now Nxera our partner, has done is what many companies in the early stages of drug discovery do when they're interested in a CNS molecule. They dial in the selectivity they desire, and then subsequent to that, they actually make the molecule be penetrant to the CNS more versus the periphery. And in doing so, when you think about 570, that's how we're able to move forward on the M1/M4 agonists without the need to add back something that blocks peripheral effects because 570 preferentially gets into the CNS.

但是 Sosei Heptares（現在是我們的 Nxera 合作夥伴）所做的另一件事是許多處於藥物發現早期階段的公司在對 CNS 分子感興趣時所做的事情。他們調整了所需的選擇性，然後，他們實際上使分子對中樞神經系統的滲透性比對周圍神經系統的滲透性更強。這樣做，當你想到 570 時，這就是我們如何能夠在 M1/M4 激動劑上取得進展，而不需要添加一些阻止外周效應的東西，因為 570 優先進入 CNS。

In terms of the ongoing program with 570 and the muscarinics, they're all in Phase I right now. They'll be reading out data during the course of 2025, and with that, we'll be able to look at the totality of the data coming from the different molecules and learn a lot from the pharmacology across M1 and M4, and with that, we'll be able to determine next steps in terms of moving the patient population.

就正在進行的 570 和毒蕈鹼計畫而言，它們目前都處於第一階段。他們將在 2025 年期間讀出數據，這樣我們就能夠查看來自不同分子的全部數據，並從 M1 和 M4 的藥理學中學到很多東西。

Okay.

好的。

Thank you.

謝謝。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi, guys. Good morning. Thanks for taking my question. On INGREZZA, you had another really strong quarter. How should we be thinking about sequentially the flow in 4Q? Because based on your guidance, it does seem like it could be a little bit flattish. I know traditionally, 4Q tends to be a stronger quarter, so can you give us a little bit of color on that? Thanks.

嗨，大家好。早安.感謝您提出我的問題。在 INGREZZA 上，您又度過了一個非常強勁的季度。我們該如何依序考慮第四季的流程？因為根據你的指導，它看起來確實有點平淡。我知道傳統上，第四季度往往是一個更強勁的季度，所以你能給我們一些關於這一點的資訊嗎？謝謝。

Yeah. I think when you look at historical sequential growth in dollars, we fall right into that historical range of somewhere between $10 and $20 million sequentially, so I do think our guidance takes that into consideration.

是的。我認為，當你觀察美元的歷史連續增長時，我們會連續陷入 1000 至 2000 萬美元之間的歷史範圍，所以我確實認為我們的指導考慮到了這一點。

Just a few comments for Q4. We do have our new field sales team that's in place and actively calling on customers and that handoff process is occurring, but as Eric said in the preparatory months, that does take a few quarters to start kicking in. And then the last piece is something that we've had in historical years, a sequential increase in gross net discount that's associated with channel inventory. It's going to be a little bit less than what it has been historically because of some of the IRA dynamics, but nonetheless, a higher gross net discount in the fourth quarter. Thank you.

只是對第四季的一些評論。我們確實有新的現場銷售團隊，他們正在積極呼叫客戶，交接過程正在進行中，但正如艾瑞克在準備幾個月中所說，這確實需要幾個季度才能開始生效。最後一點是我們在歷史上所經歷過的，與通路庫存相關的總淨折扣的連續增加。由於 IRA 的一些動態，這將比歷史水平略低一些，但儘管如此，第四季度的總淨折扣更高。謝謝。

Jay Olson, Oppenheimer.

傑·奧爾森，奧本海默。

Oh, hey. Thanks for taking the question. Congrats on all the progress. We're curious about your level of interest in epilepsy since it's still an area of super high unmet need and it's also proven to be a difficult area to conduct clinical trials, so we're just curious how committed is Neurocrine to epilepsy and do you plan to replace the Idorsia molecule with another asset? Thank you.

哦，嘿。感謝您提出問題。祝賀所有的進展。我們很好奇您對癲癇症的興趣程度，因為它仍然是一個需求未被滿足的超高領域，而且也被證明是一個難以進行臨床試驗的領域，所以我們只是好奇Neurocrine 對癲癇症的投入程度如何，您是否願意計劃用另一種資產取代 Idorsia 分子？謝謝。

Thanks, Jay. This is Kyle. I'll take the question here. We still have a very strong commitment to the area of epilepsy. We have a number of programs that are moving through various stages of preclinical development, and while I don't expect us moving forward with another T-type calcium channel blocker, we do have a mixed NaV1.2, NaV1.6 inhibitor that we're looking forward to bring up into the clinic next year, so stay tuned on that.

謝謝，傑伊。這是凱爾。我在這裡回答這個問題。我們對癲癇領域仍然有非常堅定的承諾。我們有許多項目正在經歷臨床前開發的各個階段，雖然我不希望我們繼續開發另一種 T 型鈣通道阻斷劑，但我們確實有一種混合 NaV1.2、NaV1.6 抑製劑我們期待明年進入診所，所以請繼續關注。

Obviously, a lot of the molecules that are required to move forward have a significant body of data around them for GLP Tox, 90 enabling studies. We need to get through those and then see where we land on the other side for advancing that particular asset, but still committed to epilepsy. There's still a high degree of unmet need in that space, and we hope to be a player as we move along here.

顯然，許多需要向前發展的分子都擁有大量 GLP Tox 數據，90 支持研究。我們需要解決這些問題，然後看看我們在推進這一特定資產的另一邊的位置，但仍然致力於癲癇。該領域仍有大量未滿足的需求，我們希望成為其中的一員。

That's great. Thank you.

那太棒了。謝謝。

Ash Verma, UBS.

阿什‧維爾瑪，瑞銀集團。

Hi. Thanks for taking my question. Just on 568, now that we've had some time to digest the results in Phase II, just what are you learning? Do you think this orthosteric agonism was the issue in this case, and how should we think about the rest of the muscarinic pipeline based on what you've learned? Thanks.

你好。感謝您提出我的問題。就在 568 上，既然我們已經有一些時間來消化第二階段的結果，那麼您到底學到了什麼？您認為這種正位激動是本例中的問題嗎？謝謝。

I think -- I hope I answered your question properly, Ash. I think it was that now that we have the site in Phase II data, how are we thinking about the orthosteric agonism with respect to next steps in the context of the broader muscarinic pipeline? Just to address that.

我想——我希望我正確地回答了你的問題，阿什。我認為現在我們已經有了第二階段的數據，我們如何在更廣泛的毒蕈鹼管道的背景下考慮下一步的正位激動？只是為了解決這個問題。

Yeah.

是的。

So, thank you. So just to address that, so we are moving forward rapidly with our 568 molecule on the back of the encouraging Phase II data that we saw in schizophrenia. We're planning to enter, in the first half of next year, a Phase III registration program for the treatment of schizophrenia. The first step on that journey will be our interaction at the end of Phase II with the FDA, and we're preparing for that in the next couple of months. So in that regard, we think there is a significant opportunity to add on to the current success that there's been in the muscarinic area.

所以，謝謝你。為了解決這個問題，我們在精神分裂症方面看到了令人鼓舞的 II 期數據，並迅速推進 568 分子的研究。我們計劃在明年上半年進入精神分裂症治療的三期註冊計劃。這趟旅程的第一步將是我們在第二階段結束時與 FDA 的互動，我們正在為接下來的幾個月做好準備。因此，在這方面，我們認為有一個重要的機會可以進一步鞏固毒蕈鹼領域目前所取得的成功。

We were very pleased to see the first medication approved with this mechanism in covalent earlier this quarter. But I think in terms of the selectivity for M4 and the potential benefit-risk profile and improvement in that associated with the selective agent, we believe there's a lot more room in this space to add value for patients. And so we're excited and encouraged with our Phase III planning in that regard.

我們很高興看到本季早些時候批准了第一種採用這種共價機制的藥物。但我認為，就 M4 的選擇性、潛在的益處-風險狀況以及與選擇性藥物相關的改善而言，我們相信這個領域還有更大的空間為患者增加價值。因此，我們對這方面的第三階段規劃感到興奮和鼓舞。

As Kyle mentioned, we do have a suite of muscarinic agonists behind 568, which have, again, high selectivity for either M1 or M4 as orthosteric agonists. And those are currently in Phase I development, and we're exploring how to understand the potential areas of investigation beyond Phase I as we generate data next year, which could range all the way from disorders where improvement in cognition is important, all the way through to psychosis, bipolar disorder, and other indications.

正如 Kyle 所提到的，我們確實在 568 後面有一套毒蕈鹼激動劑，它們對 M1 或 M4 作為正位激動劑具有高選擇性。這些目前正處於第一階段的開發中，當我們明年產生數據時，我們正在探索如何理解第一階段之後的潛在研究領域，這些領域可能包括從認知改善很重要的疾病到所有的領域直至精神病、雙極性情感障礙和其他適應症。

Thank you.

謝謝。

Phil Nadeau, TD Cowan.

菲爾·納多，TD·考恩。

Hi, this is Alex on for Phil. I'm for Phil. Congrats on the quarter, and thanks for taking my question. On 568, just curious if the upcoming emraclidine data on your pivotal trial plans in any way? And also, could you maybe just walk us through your broader strategy for 568's pivotal, including regulatory conversations and trial design? Thanks.

大家好，我是菲爾的亞歷克斯。我是為了菲爾恭喜本季度，感謝您提出我的問題。關於 568，只是好奇即將推出的恩拉克定數據對您的關鍵試驗計劃有何影響？另外，您能否向我們介紹您針對 568 關鍵藥物的更廣泛策略，包括監管對話和試驗設計？謝謝。

Yeah. So we actually haven't talked very much about the Phase III trial design yet, and I think we want to clear our way through the end of Phase II meetings before we do that. But certainly, as we start to post the trials that will be included in that registration program in the first half of next year, we'll be able to get into much more detail around that.

是的。因此，我們實際上還沒有過多討論第三階段試驗設計，我認為我們希望在這樣做之前在第二階段會議結束時掃清道路。但當然，當我們開始發布明年上半年將包含在該註冊計劃中的試驗時，我們將能夠更詳細地了解這一點。

With respect to the impact of emraclidine, or even [covalency] information on our planning and thinking, I think we're very encouraged by the fact that M4 cell activity appears to be sufficient to produce a psychotic effect in schizophrenia. And I think from that point of view, the fact that our model is an orthosteric agonist, that's the approach we've chosen, and that's the approach that we are confident in on the back of our Phase II data that we generated earlier this year. And so we're very much more focused on our own program in terms of understanding the emerging benefit risk from our Phase II data, and ensuring that we're incorporating all of that learning into our Phase III trial designs and into our Phase III program.

關於恩拉克定的影響，甚至是[共價]資訊對我們的計劃和思維的影響，我認為我們對 M4 細胞活性似乎足以在精神分裂症中產生精神病作用這一事實感到非常鼓舞。我認為從這個角度來看，事實上我們的模型是一種正位激動劑，這就是我們選擇的方法，也是我們在今年早些時候生成的第二階段數據的基礎上對這種方法充滿信心的方法。因此，我們更加關注我們自己的計劃，了解我們的第二階段數據中出現的收益風險，並確保我們將所有這些知識納入我們的第三階段試驗設計和第三階段計劃中。

And we'll be happy to talk more about that as we see it through the end of Phase II interaction with the FDA.

當我們看到與 FDA 的第二階段互動結束時，我們將很樂意更多地討論這一點。

And maybe just to add to that, the excitement that we have around our own program stems from the fact that we're the only approach that can selectively and directly activate M4 and deliver on the promise that we've seen from the muscarinics thus far without any need to rely on any other aspect of an add-back therapy or some sort of endogenous ligand for either efficacy or safety or tolerability. We think at the end of the day, physicians are going to be feeling a lot more confident about our approach being able to be used than the wider population of the patients.

也許補充一點，我們對自己的計劃感到興奮源於這樣一個事實：我們是唯一能夠選擇性地直接激活 M4 並兌現我們迄今為止從毒蕈鹼藥物中看到的承諾的方法無需依賴回加療法的任何其他方面或某種內源性配體來實現功效、安全性或耐受性。我們認為最終，醫生會對我們的方法能夠比更廣泛的患者群體使用更有信心。

Thank you.

謝謝。

Thank you.

謝謝。

Anupam Rama, J.P. Morgan.

阿努帕姆‧拉瑪 (Anupam Rama)，J.P. 摩根。

Hey, guys. Thanks so much for taking the question. I'm going to ask the same question I've asked for the last 10 years on third-quarter earnings. So any chance of an INGRESA pre-announce and guidance at a Smart Healthcare Conference in January? Or is this more of a fourth-quarter earnings report scenario in February?

嘿，夥計們。非常感謝您提出問題。我將問過去十年來關於第三季收益的同樣的問題。那麼 INGRESA 在 1 月的智慧醫療會議上有機會預先宣布並提供指導嗎？還是這更像是二月第四季財報的情景？

Yeah. Anupam, I can pick up a trend without you even acknowledging it. So always good to hear your questions. We're obviously looking forward to J.P. Morgan this year. Kyle has an ambitious plan for 2025 with full detail. But as consistent with the last, I believe, two years, this will be the third year where we do not pre-announce our revenue at the J.P. Morgan conference. And we'll save commentary for both Q4 results and then for your sales guidance for 2025 until our February earnings call. But always glad to see you in January to kick off the New Year.

是的。Anupam，我甚至可以在你不知情的情況下發現趨勢。很高興聽到您的問題。我們顯然對今年的摩根大通充滿期待。凱爾 (Kyle) 為 2025 年制定了一個雄心勃勃的計劃，並提供了完整的細節。但我相信，與過去兩年一樣，這將是我們第三年不在摩根大通會議上預先公佈我們的收入。我們將保留對第四季度業績的評論，然後保留對 2025 年銷售指導的評論，直到我們 2 月的財報電話會議為止。但總是很高興在一月見到你，開啟新年。

Thank you.

謝謝。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO 資本市場。

Hi, guys. Great. Thank you so much for taking my question. So, you know, as we think about your salesforce expansion and the opportunities for treatment of Chorea associated with Huntington's disease, how should we really frame that opportunity? I know Eric’s been there. But, you know, with the investment, where do you see, I guess, INGREZZA going in the next couple of years? I mean, how does this really compare with the TD market? I think secondarily, why focus on epidemiology for TD now? Does that imply that, you know, you're not satisfied with where TD is going? You know, you're trying to emphasize that there's still more room to grow. I'm just trying to get a better understanding of what that commercial story looks like.

嗨，大家好。偉大的。非常感謝您回答我的問題。所以，您知道，當我們考慮您的銷售團隊擴張以及治療與亨廷頓舞蹈症相關的舞蹈病的機會時，我們應該如何真正抓住這個機會？我知道艾瑞克去過那裡。但是，你知道，透過這項投資，我想你認為 INGREZZA 在未來幾年會走向何方？我的意思是，這與 TD 市場相比如何？我想其次，為什麼現在要關注 TD 的流行病學？這是否意味著您對 TD 的發展方向不滿意？你知道，你試著強調還有更多的成長空間。我只是想更好地理解這個商業故事是什麼樣的。

Yeah, let me take your second question first in terms of our reassessment of the prevalence of TD. And, you know, that's something that we haven't looked at for a number of years. And so, you know, I would look at that as more of just an updating our prevalence estimates, you know, using a methodology that's similar and consistent with what we had done previously. The time that we launched in 2017, our estimate was at least 500,000 people in the U.S. with TD. A couple of years later, we updated our estimate to at least 600,000. And fast forward, I think it's been four or five years since the last time we looked at it.

是的，讓我先回答你的第二個問題，即我們對 TD 盛行率的重新評估。而且，你知道，我們已經很多年沒有關注這個問題了。因此，我認為這更多地只是更新我們的盛行率估計，使用與我們之前所做的類似且一致的方法。2017 年推出時，我們估計美國至少有 50 萬人患有 TD。幾年後，我們將估計值更新為至少 60 萬人。時間快進，我想距離我們上次查看它已經有四到五年了。

And, you know, the numbers of people living with TD continue to grow, I think commensurate with the expanded use of antipsychotics, especially in non-psychotic conditions. And so, in our prepared remarks, we did update the number now to at least 800,000 people with TD in the U.S. And I think that that number is similar to other estimates that are out there and, frankly, maybe a little bit on the low end of the range. So, that's the prevalence story.

而且，你知道，患有 TD 的人數持續增長，我認為這與抗精神病藥物的擴大使用相稱，特別是在非精神病情況下。因此，在我們準備好的發言中，我們現在確實將美國 TD 患者的數量更新為至少 800,000 人。這就是流行的故事。

In terms of the sales team, you know, we certainly felt like the decision to expand our salesforce was in line with the growth of the market. And certainly, as I mentioned in the prepared remarks, consistent with the growth of the prescriber base in TD. And in terms of Huntington, the only part of our commercial team that we didn't expand or change, really, was the neurology team. And the strategy of penetrating that Huntington's opportunity is primarily through our neurology salesforce. On a relative basis, the neurology opportunity is much smaller, excuse me, the Huntington's opportunity is a lot smaller than it is in Tardive Dyskenisia. And yet, there's still significant unmet need in Huntington's Chorea.

就銷售團隊而言，您知道，我們當然認為擴大銷售團隊的決定符合市場的成長。當然，正如我在準備好的發言中提到的，這與 TD 處方者基礎的增長是一致的。就亨廷頓而言，我們商業團隊中唯一沒有擴展或改變的部分實際上是神經病學團隊。滲透亨廷頓機會的策略主要是透過我們的神經病學銷售團隊。相對而言，神經病學的機會要小得多，對不起，亨廷頓舞蹈症的機會比遲發性運動障礙要小得多。然而，亨廷頓舞蹈症仍有大量未滿足的需求。

You may have seen that we've recently presented some data showing the use of INGREZZA in patients that are with Huntington's Chorea a that are also on antipsychotics. And I think that that's some important data to get out there because that is a segment of patients with Huntington's Chorea that are typically not treated with VMAT2 inhibitors. And so, we wanted to show that they have no impact on relative safety, but they can still improve their Chorea movements.

您可能已經看到，我們最近提供了一些數據，顯示 INGREZZA 在同時服用抗精神病藥物的亨廷頓舞蹈症患者的使用情況。我認為這是一些重要的數據，因為這部分亨廷頓舞蹈症患者通常不接受 VMAT2 抑制劑治療。因此，我們想證明它們對相對安全性沒有影響，但它們仍然可以改善舞蹈動作。

And so, overall, the growth driver in the future will continue to be primarily TD, but Huntington's is still an important strategic opportunity for us, especially within the framework of our neurology team.

因此，總體而言，未來的成長動力仍將主要是 TD，但亨廷頓舞蹈症對我們來說仍然是一個重要的策略機會，特別是在我們的神經病學團隊的框架內。

Maybe just to put a finer point on that, we talked about the TD prevalence being around 800,000 in the US for HD Chorea, there's about 30,000 patients, about 20,000 patients have Chorea that's moderate to severe, about 5,000 patients currently on a VMAT2 inhibitor. So, the 15,000 patients that we're looking to address, that's about a 50 to 1 ratio of patients that we can serve with INGREZZA when you look at the opportunity versus TD. So, we do feel that the greater opportunity moving forward will be in Tardive Dyskenisia, but we'd like to penetrate more into the HD Chorea space, in particular with the launch of our INGREZZA Sprinkle to help access patients who might have difficulty swallowing or dysphagia that tends to be more prevalent in the HD population.

也許只是為了更詳細地說明這一點，我們談到美國HD Chorea 的TD 盛行率約為800,000，大約有30,000 名患者，大約20,000 名患者患有中度至重度舞蹈病，大約5,000 名患者目前正在服用VMAT2 抑制劑。因此，當您考慮機會與 TD 時，我們希望解決的 15,000 名患者中，我們可以使用 INGREZZA 服務的患者比例約為 50 比 1。因此，我們確實認為，更大的機會將出現在遲發性運動障礙領域，但我們希望更多地滲透到HD Chorea 領域，特別是推出我們的INGREZZA Sprinkle，以幫助治療吞嚥困難或吞嚥困難的患者。

Thank you.

謝謝。

Cory Kasimov, Evercore.

科里·卡西莫夫，Evercore。

Hey, good morning, guys. Thanks for taking the question. I wanted to ask about Crinecerfont, and if you can talk about how many prescribers are located at the CAH Centers of Excellence and the portion of the overall patient population they serve, and are there certain segments of the CAH population they are most eager to treat upon approval? Thank you.

嘿，早上好，夥計們。感謝您提出問題。我想詢問 Crinecerfont 的情況，您能否談談 CAH 卓越中心有多少名處方醫生以及他們所服務的總體患者群體的比例，以及他們最渴望治療的 CAH 人群中的某些部分經批准後?謝謝。

Yeah. So, let me take a step back and say that we're really excited about the opportunity to make a difference with the CAH community. With the PDUFA date coming up here at the end of the year, we've been preparing for a launch early in 2025. As you know, we have a salesforce that's out there. They're doing disease state education right now. They're meeting with future customers. They're profiling and learning about their practices. And so, this is all important work that will help us get off to a strong start once we, knock on wood, get approval later this year.

是的。所以，讓我退一步說，我們真的很高興有機會為 CAH 社群帶來改變。隨著 PDUFA 日期在今年年底到來，我們一直在為 2025 年初的發布做準備。如您所知，我們有一支銷售團隊。他們現在正在進行疾病狀態教育。他們正在與未來的客戶會面。他們正在分析並了解他們的實踐。因此，這些都是重要的工作，一旦我們在今年稍後獲得批准，它們將幫助我們有一個良好的開始。

In terms of the proportion of the patient population that's within the care of the centers, the CARES Foundation Centers of Excellence, there's only about a dozen or so of those Centers of Excellence out there. And we're still learning about what proportion of the patient population are being managed through those centers. But I would say it's in the range of 10% to 15% of patients in total. And so the majority of patients with CAH are still being cared for within community endocrinology practices and also within pediatric endocrinology practices.

就這些中心（即 CARES 基金會卓越中心）護理的患者群體的比例而言，此類卓越中心大約只有十幾個。我們仍在了解有多少比例的患者正在透過這些中心進行管理。但我想說，這種情況佔患者總數的 10% 到 15%。因此，大多數 CAH 患者仍在社區內分泌科和兒科內分泌科接受護理。

So obviously, we are going to be putting a lot of focus early on those two segments, the pediatric endocrinologists as well as the CARES Centers. But ultimately, for us to really make a difference in this patient population, we're going to have to make sure that we also are reaching out to those patients that are cared for in community endocrinology practices.

顯然，我們將儘早將重點放在這兩個部分，即兒科內分泌科醫生和 CARES 中心。但最終，為了讓我們真正為這個患者群體帶來改變，我們必須確保我們也接觸到那些在社區內分泌實踐中得到照護的患者。

Do you have anything else to add, Eiry?

艾瑞，你還有什麼要補充的嗎？

No, I think you said it well, Eric. mean, I think there is a lot of excitement that we're hearing as we're talking with clinicians who are working with these patients given that there's been nothing new for this patient population in the last 70 years. And we do know in terms of focus that in the pediatric setting, obviously there is a very significant level of interest in a potential medication that could help with androgen reduction in that patient population where very tight management of androgen levels becomes so critical in the face of normal growth and development.

不，我認為你說得很好，艾瑞克。意思是，我認為，當我們與治療這些患者的臨床醫生交談時，我們聽到了很多令人興奮的聲音，因為在過去 70 年裡，對於這些患者群體來說沒有什麼新鮮事。我們確實知道，在兒科環境中，顯然人們對一種潛在的藥物非常感興趣，這種藥物可以幫助減少患者群體中的雄激素，在這些患者群體中，嚴格控制雄性激素水平變得非常重要。的正常生長和發育。

And so we are seeing a lot of, a very significant interest as we continue to hopefully progress towards an approval for both pediatric and adult patients living with congenital adrenal hypoplasia by the end of this year.

因此，我們看到了很多非常重要的興趣，因為我們希望在今年年底前繼續取得對患有先天性腎上腺發育不全的兒童和成人患者的批准。

Eric, you had something else?

艾瑞克，你還有別的事嗎？

Oh, yeah, just one last thing I want to say is that our team, the receptivity that we've seen since our team has gone out into the field since this summer has been really strong. So I think there's really great interest in the endocrinology community, and certainly I think it's a testament to the unmet need in CAH.

哦，是的，我想說的最後一件事是，我們的團隊，自今年夏天以來我們的團隊進入該領域以來所看到的接受度非常強。所以我認為內分泌學界確實非常感興趣，當然我認為這證明了 CAH 的需求尚未得到滿足。

That's helpful. Thank you.

這很有幫助。謝謝。

Thank you.

謝謝。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

Hi, this is Luke on for Brian. With the upcoming pivotal trials in psychiatry, should we expect 845 and 568 to progress largely in parallel following the end of Phase II meetings, or will you be looking to emphasize or accelerate one program over the other? Thanks.

大家好，我是布萊恩的盧克。隨著即將到來的精神病學關鍵試驗，我們是否應該期望 845 和 568 在第二階段會議結束後基本上並行進展，或者您是否會尋求強調或加速一個項目而不是另一個項目？謝謝。

I appreciate the question. I think given the proximity of when we reported top-line data would be commensurate with how we would look at starting the Phase III trials in 2025. We don't anticipate any need to stagger them in any particular way for any reason. It's going to be more based on when we have our end of Phase II discussions and then we can stand up the pivotal trials for both 845 and 568. So I expect them to be started nearly at a similar timeframe, but not at the exact time for both of these studies.

我很欣賞這個問題。我認為，考慮到我們報告頂線數據的時間臨近，將與我們如何考慮在 2025 年開始 III 期試驗相稱。我們預計不需要出於任何原因以任何特定方式錯開它們。這將更取決於我們何時結束第二階段的討論，然後我們才能經受 845 和 568 的關鍵試驗。因此，我預計它們將在幾乎相似的時間範圍內開始，但不是在這兩項研究的確切時間。

The other thing I'd ask there, Kyle, is that obviously from an operational perspective as well, these are focused on two different indications within the psychiatry space with 845 in major depressive disorder and 568 in schizophrenia. So we don't anticipate competitions for patients between our two programs, which I think is really important. And the internal team is extremely

凱爾，我要問的另一件事是，顯然從操作的角度來看，這些研究也集中在精神病學領域的兩種不同的適應症上，其中845 例屬於重度憂鬱症，568 例屬於精神分裂症。因此，我們預計兩個項目之間不會出現患者競爭，我認為這非常重要。而且內部團隊非常

excited about the opportunity to potentially bring value in both of these areas with these programs, moving forward.

很高興有機會透過這些計劃在這兩個領域帶來潛在的價值，並繼續前進。

Carter Gould, Barclays.

卡特·古爾德，巴克萊銀行。

Good morning. Thanks for taking the question. Maybe to follow up on one of the earlier questions some time ago in the queue. I guess for a long time we looked at Neurocrine’s pipeline, you guys were sort of mid-stage heavy. That's clearly evolved. And now it's a little bit more of, I guess, a barbell approach where you've clearly made those Phase III investments or about to make those Phase III investments. And the earlier stage pipeline now, at least from kind of where we sit, seems very focused on VMATs and muscarinics. So can you maybe talk about how you're looking at that early stage portfolio? I guess the breadth and diversity of those assets and should we expect sort of another replenishment either through in-licensing or homegrown assets to sort of bubble up over the course of ’25?

早安.感謝您提出問題。也許是為了跟進隊列中早些時候提出的問題之一。我想我們在研究 Neurocrine 的流程很長一段時間裡，你們都處於中期階段。這顯然是進化而來的。我想，現在它更像是一種槓鈴方法，您已經明確進行了第三階段投資或即將進行第三階段投資。現在的早期階段管道，至少從我們所處的位置來看，似乎非常關注 VMAT 和毒蕈鹼。那麼您能否談談您如何看待早期投資組合？我猜想這些資產的廣度和多樣性，我們是否應該期望透過許可或本土資產進行另一次補充，以在 25 年內出現泡沫？

Yeah, thanks for the question. I think also we'd like to point out that in addition to the later stage assets and the earlier portfolio that you mentioned that spans the muscarinic agonists and VMAT2, we also have a muscarinic antagonist that we're moving forward for a variety of movement disorders and then in Phase II we have an NR2D NAM that we're moving forward with major depressive disorder. So there's a lot going on across the organization in terms of early to the late stage portfolio. And we'll have more to say about what's emerging in terms of our earlier stage portfolio and add to the clinical programs in early 2025. So stay tuned on that. There's a lot of productivity that's ongoing right now in our labs and it just takes a bit of time to move that forward into clinic and we'll start seeing that in 2025.

是的，謝謝你的提問。我想我們還想指出，除了後期資產和您提到的涵蓋毒蕈鹼激動劑和 VMAT2 的早期投資組合外，我們還有毒蕈鹼拮抗劑，我們正在推進各種行動然後在第二階段，我們有一個NR2D NAM，我們正在推進重度憂鬱症的治療。因此，整個組織在早期到後期的投資組合方面發生了很多事情。我們將更多地介紹我們早期產品組合中出現的情況，並在 2025 年初添加到臨床項目中。所以請繼續關注。我們的實驗室目前正在不斷提高生產力，只需一些時間即可將其推進到臨床，我們將在 2025 年開始看到這一點。

Understood. Thank you.

明白了。謝謝。

Thank you.

謝謝。

Brian Abrahams, RBC Capital Markets.

布萊恩‧亞伯拉罕斯 (Brian Abrahams)，加拿大皇家銀行資本市場部。

Hi, this is Joe in for Brian. Thank you for taking our question. Can you elaborate more on the growth drivers you're seeing on INGREZZA, the degree of demand versus gross to net versus any other contributions you could note for us and how are you thinking about -- what are you seeing on the ground in terms of the competitive landscape in the TD market? Thank you.

嗨，我是喬，替補布萊恩。感謝您提出我們的問題。您能否詳細說明您在 INGREZZA 上看到的成長動力、需求程度與毛淨值對比以及您可以為我們指出的任何其他貢獻，以及您是如何考慮的——您在實地看到了什麼？競爭格局如何？謝謝。

Yeah, in terms of the dynamics for Q3, it's primarily driven, the growth is primarily driven by demand and as I mentioned in my prepared remarks, continued strong compliance for INGREZZA. In terms of the competitive dynamics, this is a growing market and obviously, we've seen strong growth since we launched seven years ago and counting. As Kyle mentioned in his prepared remarks, less than 20% of patients are currently being treated with a VMAT2 inhibitor, which are the recommended first line treatment in the treatment guidelines.

是的，就第三季的動態而言，它主要是由需求驅動的，正如我在準備好的發言中提到的那樣，INGREZZA 繼續保持強勁的合規性。就競爭動態而言，這是一個不斷成長的市場，顯然，自七年前推出以來，我們已經看到了強勁的成長，並且還在持續成長中。正如 Kyle 在他準備好的發言中提到的，目前只有不到 20% 的患者正在接受 VMAT2 抑制劑治療，這是治療指南中建議的一線治療方法。

So there's still a long opportunity ahead of us with 14 more years of exclusivity and we continue to invest in that growth, I think, as indicated by the recent expansion of our field sales team and our continued investment in DTC. So, growth is primarily organic and will continue to be for the foreseeable future.

因此，我們前面還有很長的機會，可以再擁有14 年的獨家經營權，我認為，我們將繼續投資於這種增長，正如我們最近擴大的現場銷售團隊和我們對DTC 的持續投資所表明的那樣。因此，成長主要是有機成長，並且在可預見的未來仍將持續。

Got it. Thank you.

知道了。謝謝。

Thank you.

謝謝。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

Great. Thank you very much for taking my question and Kyle, congrats on your first call as a CEO. Maybe, would love to understand how internally you are thinking about, the upcoming competition in CAH space. I mean, kind of we are probably putting cards before the horse here, but there is an ACTH antagonist out there as well. How do you see that as a competitor to Crinecerfont? Do you see this as a direct competitor or more like in lines of therapy where something could be first line versus second line? How do you -- how should you think about that?

偉大的。非常感謝您回答我的問題，凱爾，祝賀您作為首席執行官第一次致電。也許，很想了解您內部如何看待 CAH 領域即將到來的競爭。我的意思是，我們可能是在本末倒置，但那裡也有一個 ACTH 拮抗劑。作為 Crinecerfont 的競爭對手，您如何看待它？您認為這是直接競爭對手還是更像一線治療與二線治療？你如何－你應該如何考慮這個問題？

Maybe I'll start that question if there's anything I'm missing, I'll ask my team to chime in here. So when we think about CAH, I think we can all agree that this is a very serious disease. You know, at the heart of the matter is the body's struggle to capture its HPA axis. And by HPA, I mean the hypothalamus-pituitary-adrenal axis. In terms of how the disease is initiated, it's caused by mutations on the CYP21A2 gene and that results in dysfunction or absence of the synthesis of cortisol, which is the key regulator of the HPA axis.

如果我遺漏了什麼，也許我會開始這個問題，我會請我的團隊在這裡插話。因此，當我們想到 CAH 時，我想我們都同意這是一種非常嚴重的疾病。您知道，問題的核心是身體努力捕捉 HPA 軸。我所說的 HPA 是指下視丘-腦下垂體-腎上腺軸。就疾病的發生方式而言，它是由 CYP21A2 基因突變引起的，導致皮質醇合成功能障礙或缺乏，而皮質醇是 HPA 軸的關鍵調節因子。

So for the past 70 years, patients, physicians have used super physiological or very high doses of GC glucocorticoids to act as that regulator of the HPA axis. What we get with Crinecerfont is the ability for the patient to capture or recapture their HPA axis, allows them to control ACTH, reduce ACTH and therefore control -- reduce and control of your androgens.

因此，在過去的 70 年裡，患者、醫生使用超生理劑量或非常高劑量的 GC 糖皮質激素來充當 HPA 軸的調節劑。我們透過 Crinecerfont 獲得的是患者能夠捕獲或重新捕獲他們的 HPA 軸，使他們能夠控制 ACTH、減少 ACTH，從而控制——減少和控制雄激素。

And at the same time we think about that, when you control ACTH, the androgens are able to

同時我們想到，當你控制促腎上腺皮質激素時，雄性激素能夠

remove the requirement for excessive control of your -- excessive use of glucocorticoids and we've seen it from our Phase III trials that that puts a little number of patients into using a physiological range of their GC dose.

消除過度控製糖皮質激素的要求，我們從 III 期試驗中看到，這讓少數患者使用了生理範圍的 GC 劑量。

When we think about the competition then, our approach uses the angle of working upstream at the HPA axis to control the regulation of the HPA at the top and then everything below that we're able to reduce the control as well, starting with ACTH. Our competitor in this space, a company here in San Diego that we know quite well, Crinetics' is developing an ACTH antagonist called Atumelnant and it's an early stage clinical development right now with a small

當我們考慮競爭時，我們的方法使用 HPA 軸上游的工作角度來控制頂部 HPA 的調節，然後我們也可以從 ACTH 開始減少對下面的所有內容的控制。我們在這個領域的競爭對手是一家位於聖地牙哥的公司，我們對此非常了解，Crinetics 正在開發一種名為 Atumelnant 的 ACTH 拮抗劑，目前處於早期臨床開發階段，還需要小規模臨床試驗。

number of subjects.

科目數。

And the time will tell to see how their approach will work relative to ours because they actually work downstream of our approach. So they only look at the androgens, not the other piece of the cascade which is ACTH. But ultimately where we are right now, we're very excited about our position. We've got very strong efficacy across both children and adults. We've got excellent safety and tolerability and we have formulations that match the needs of both children and adults.

時間會告訴我們他們的方法相對於我們的方法將如何發揮作用，因為他們實際上在我們方法的下游工作。因此，他們只關注雄性激素，而不關注級聯的另一部分，即促腎上腺皮質激素。但最終我們現在所處的位置，我們對我們的地位感到非常興奮。我們對兒童和成人都有很強的療效。我們具有出色的安全性和耐受性，我們的配方能夠滿足兒童和成人的需求。

So we feel like we're in a very fortunate position here and we look forward to hopefully getting approval later this year and launching this important medicine for patients which is going to change the standard of care in CAH.

因此，我們覺得我們處於一個非常幸運的位置，我們期待今年稍後獲得批准，並為患者推出這種重要的藥物，這將改變 CAH 的護理標準。

Excellent. Thank you.

出色的。謝謝。

Thank you.

謝謝。

Marc Goodman, Leerink Partners.

馬克古德曼，Leerink Partners。

Yeah, I just want to come back to that question about aggressive competition in the competitive environment. There seems to be a lot of agita going into the quarter. A lot of investors kind of felt that Teva's been the one growing faster. They're making more noise. Can you give us a sense of what's really going on out there? You know, do you feel like you're outgunned with respect to the share of voice and the noise on the media? Maybe you could just give us a sense there. I think the prescription trends have really confused people. So anything you could do to help us just think about this. Thank you.

是的，我只想回到關於競爭環境中激烈競爭的問題。本季似乎有很多令人不安的事情。許多投資者都覺得梯瓦製藥（Teva）的成長速度更快。他們製造更多噪音。你能讓我們了解那裡到底發生了什麼事嗎？你知道，你是否覺得自己在媒體上的聲音和噪音方面處於劣勢？也許你可以給我們一個感覺。我認為處方趨勢確實讓人們感到困惑。所以你可以做任何事情來幫助我們思考這個問題。謝謝。

Yeah, I mean, obviously we felt good about the quarter we just reported. As I mentioned before, the VMAT2 market is a growing market. The vast majority of TD patients remain undiagnosed and untreated. Both brands are growing and as expected with the rollout of their XR formulation of deutetrabenazine, it's helped the growth of our competitor. However, INGREZZA is and it remains the most prescribed VMAT2 inhibitor with over a million prescriptions written since launch. And with 14 more years of exclusivity ahead, we believe strongly in the growth of the potential of INGREZZA and continue to invest in our franchise commensurate with the opportunity.

是的，我的意思是，顯然我們對剛剛報告的季度感覺良好。正如我之前提到的，VMAT2 市場是一個不斷成長的市場。絕大多數 TD 患者仍未得到診斷和治療。這兩個品牌都在成長，正如預期的那樣，隨著其 XR 氘代丁苯那嗪配方的推出，它幫助了我們競爭對手的成長。然而，INGREZZA 仍然是處方最多的 VMAT2 抑制劑，自去年以來已開出超過 100 萬張處方。未來還有 14 年的獨家經營權，我們堅信 INGREZZA 的潛力將持續成長，並將繼續投資與機會相稱的特許經營權。

And I think the testament to that is the recent salesforce expansion that we just completed. As I mentioned in my prepared remarks, specifically in psychiatry, and in LTC. Psychiatry is the area that we didn't touch when we expanded our team back in 2022. And we felt that with the growth of the prescriber base, we were overdue in terms of adding more FTEs there to continue to support that segment. LTC is a relatively newer segment for us and certainly it's been fast growing and we think that the investment there was appropriate.

我認為我們最近剛完成的銷售團隊擴張就證明了這一點。正如我在準備好的演講中提到的，特別是在精神病學和長期護理中心。精神病學是我們在 2022 年擴大團隊時沒有觸及的領域。我們認為，隨著處方者基礎的成長，我們早就該增加更多 FTE 來繼續支持該細分市場。LTC 對我們來說是一個相對較新的領域，當然它一直在快速成長，我們認為那裡的投資是合適的。

So overall, with continued investment in our team and in DTC and other areas of promotion, we think that this is a sign of the conviction that we have in the current and the long-term opportunity with INGREZZA.

因此，總的來說，隨著對我們團隊、DTC 和其他推廣領域的持續投資，我們認為這表明我們對 INGREZZA 當前和長期的機會充滿信心。

Thank you.

謝謝。

Myles Minter, William Blair.

邁爾斯·明特，威廉·布萊爾。

Hey, thanks for taking the question. I think just over a week ago there was some correspondence in the New England Journal about Crinecerfont from a couple of Spanish docs and they were kind of calling in a question the definition you use for normal thresholds of daily glucocorticoid “dosing”. Just curious as to your response to that and if payers in particular in your early conversations are asking for surrogate metrics like insulin resistance and percent of total fat masses, sort of confirmatory endpoints that you are getting efficacy in this population? Thanks.

嘿，謝謝你提出問題。我想就在一個多星期前，《新英格蘭雜誌》上有幾封來自幾位西班牙醫生關於Crinecerfont 的信件，他們提出了一個問題，即您對每日糖皮質激素正常閾值“劑量”使用的定義。只是好奇您對此的反應，以及付款人（尤其是在您早期對話中）是否要求提供胰島素阻抗和總脂肪量百分比等替代指標，以及您在該人群中獲得療效的確認終點？謝謝。

Yeah, thanks, Myles. So, first of all, I think we were really happy with the Phase III data that we have both from an efficacy perspective in terms of the androgen reduction effect of Crinecerfont and the ability to reduce steroids in the vast majority of the population treated. And that's the case in both the pediatric and the adult population.

是的，謝謝，邁爾斯。因此，首先，我認為我們對 III 期數據感到非常滿意，從療效角度來看，Crinecerfont 的雄激素減少作用以及在絕大多數接受治療的人群中減少類固醇的能力都是如此。兒童和成人都是如此。

Now, in terms of the discussion in the New England Journal and I think it's important that there's a discussion around what criteria were used in a clinical trial, etc. But I want to remind you this is the first time a trial of this sort has ever been done. And so we negotiated very closely with the Agency to come to the set of definitions that were used including the definition of what constitutes physiologic levels of GC. And that was important because this is a highly heterogeneous population. And so I think our bottom line from the Crinecerfont data set that we generated is that we really believe that the vast majority of patients living with CAH, whether they be pediatric or adult patients, can gain benefits from treatment of Crinecerfont if and when it's approved.

現在，就《新英格蘭雜誌》的討論而言，我認為圍繞臨床試驗中使用的標準等進行討論很重要。因此，我們與 FDA 進行了非常密切的談判，以達成所使用的一套定義，包括 GC 生理水平的定義。這很重要，因為這是一個高度異質的人群。因此，我認為我們產生的 Crinecerfont 資料集的底線是，我們確實相信絕大多數患有 CAH 的患者，無論是兒科患者還是成人患者，如果 Crinecerfont 獲得批准，都可以從 Crinecerfont 的治療中獲益。

And so from that point of view, we're highly encouraged and I think it's going to be very important to understand the real world experience of patients once we start to get out into this chronic condition and once we start to see the long term benefits that can result from a treatment like Crinecerfont.

因此，從這個角度來看，我們深受鼓舞，我認為一旦我們開始擺脫這種慢性病並且一旦我們開始看到長期益處，了解患者的真實體驗將非常重要這可以透過像 Crinecerfont 這樣的治療來實現。

Thank you.

謝謝。

Jeffrey Hung, Morgan Stanley.

傑弗裡洪，摩根士丹利。

Hi. This is Michael Riad on for Jeff Hung. Thank you for taking our questions and Kyle, congrats on the strong start. For the NMDA-NR2B program, is it safe to assume that 770 is being developed as an adjunct to background antidepressants? And if so, how are you thinking about evaluating the top line? What would you want to see to gauge the competitive potential like maybe versus SPRAVATO? Thank you.

你好。我是邁克爾·裡亞德 (Michael Riad) 代表傑夫·洪 (Jeff Hung)。感謝您接受我們的問題，凱爾，祝賀您的良好開端。對於 NMDA-NR2B 計劃，可以安全地假設 770 正在開發作為背景抗憂鬱藥物的輔助藥物嗎？如果是這樣，您如何考慮評估營收？您希望看到什麼來衡量競爭潛力，例如與 SPRAVATO 相比？謝謝。

So yes, in the context of the trial that's being performed right now in Phase II, the patient population is those who have inadequate response to currently available antidepressants. That actually could in due course be both as an adjunctive treatment or potentially as a standalone monotherapy. One of the key differentiators from this obviously is a mechanism that acts in a similar fashion to ketamine but being more selective in terms of the mechanism of action, we hope could translate into a favorable benefit risk profile relative to other treatments in this phase.

所以，是的，在目前正在進行的第二階段試驗中，患者群體是那些對目前可用的抗憂鬱藥物反應不足的人。實際上，在適當的時候，這既可以作為輔助治療，也可以作為獨立的單一療法。顯然，與此的關鍵區別之一是其作用機制與氯胺酮類似，但在作用機制方面更具選擇性，我們希望在這一階段能夠轉化為相對於其他治療方法有利的獲益風險狀況。

One key differentiator is this is an oral mechanism obviously compared to some of the other things that are out there right now.

一個關鍵的區別是，與目前存在的其他一些東西相比，這顯然是一種口頭機制。

Thank you. That's very helpful.

謝謝。這非常有幫助。

Good morning. Thank you very much for taking the question. Just with respect to the 800,000 TD revision there, could you provide additional color in terms of the breakdown of severity or kind of estimates within there? I guess I'm trying to understand how does this impact or change your views on the peak INGREZZA opportunity in Tardive Dyskinesia? Thank you.

早安.非常感謝您提出問題。就 800,000 TD 修訂版而言，您能否提供有關嚴重性細分或其中估計類型的更多資訊？我想我想了解這如何影響或改變您對遲發性運動障礙 INGREZZA 高峰機會的看法？謝謝。

Yeah, we don't have any color in terms of severity. Overall, when you look at the literature the estimate is that about half to two-thirds of patients would be in that moderate to severe category and the balance being milder TD. So in the medical literature there's really no standard definition of what constitutes mild, moderate, or severe TD. And so ultimately the guidance that we give to the CP community is that not only do they need to look for abnormal movements and differentiate TD from other drug and movement disorders, but they really need to look at the patient and have a conversation with the patient and understand to what extent does that impact their quality of life and their functionality.

是的，我們在嚴重性方面沒有任何顏色。總體而言，當您查看文獻時，估計大約一半到三分之二的患者屬於中度至重度類別，其餘為輕度 TD。因此，在醫學文獻中，對於輕度、中度或重度 TD 的構成實際上沒有標準定義。因此，最終我們給 CP 社區的指導是，他們不僅需要尋找異常運動並將 TD 與其他藥物和運動障礙區分開來，而且他們確實需要觀察患者並與患者進行對話並了解這在多大程度上影響他們的生活品質和功能。

And even milder abnormal movements can significantly negatively impact these patients. And so what you see in terms of people that are being treated with INGREZZA today is a mixture of people with more severe and less severe abnormal movements, but certainly significantly negatively impacting their lives. So in terms of the overall population you know we feel that the 800,000 number is like I said very supportable and frankly probably on the more conservative end of the range of estimates that are out there. But ultimately our mission remains unchanged. Less than 20% of people are currently being treated with VMAT2 inhibitors and we've got a lot of growth opportunity ahead.

即使是較輕微的異常運動也會對這些患者產生顯著的負面影響。因此，在您今天看到的接受 INGREZZA 治療的患者中，既有較嚴重的異常運動，也有不太嚴重的異常運動，但肯定對他們的生活產生了重大負面影響。因此，就總人口而言，我們認為 800,000 的數字就像我說的那樣非常有依據，而且坦白說，可能處於現有估計範圍中較為保守的一端。但最終我們的使命保持不變。目前只有不到 20% 的人正在接受 VMAT2 抑制劑治療，我們未來還有很多成長機會。

Thanks very much.

非常感謝。

Thank you.

謝謝。

Yatin Suneja, Guggenheim.

亞汀‧蘇內賈 (Yatin Suneja)，古根漢。

Hi this is Thelma for Yatin. Congrats on the quarter and thanks for taking our question. So on the 845 in MDD, can you guide us through your strategy for the pivotal program? How many studies are you planning to run? And can we expect to see Phase II data at any upcoming conference? Thank you.

大家好，我是雅汀的賽爾瑪。恭喜本季度，感謝您提出我們的問題。那麼，關於 MDD 的 845，您能否引導我們了解您的關鍵規劃策略？您計劃進行多少項研究？我們可以期望在即將舉行的會議上看到第二階段的數據嗎？謝謝。

Thanks for that. So in terms of the actual program design for Phase III, obviously we'll be following the path that's been followed by other antidepressants in registrational development but we haven't talked specifically about number of trials or designs of trials and we will do that after we have engaged in our end of Phase II interaction with the FDA and are starting those trials next year. And yes I think we alluded to in our early comments we are planning to release the information from our Phase II program in the latter part of next year.

謝謝你。因此，就第三階段的實際項目設計而言，顯然我們將遵循其他抗憂鬱藥物在註冊開發中所遵循的路徑，但我們還沒有具體討論試驗數量或試驗設計，我們將在之後進行我們已經結束了與FDA 的第二階段互動，並將於明年開始這些試驗。是的，我認為我們在早期評論中提到，我們計劃在明年下半年發布第二階段計劃的資訊。

Thank you.

謝謝。

Thank you.

謝謝。

Uy Ear, Mizuho.

Uy Ear，瑞穗。

Hey guys. Thanks for taking my question. Just going back to the Crinecerfont launch. You guys indicated there you’ll be giving our free drugs, what not? Before the insurance comes on, just maybe just help us understand a bit about the number of patients that are currently on free drugs at the moment with your extension safety extension studies, and how do you sort of maybe focus on in terms of uptakes? Would you be giving free drugs essentially to everyone that comes on or yeah, just want to get maybe a better sense of the demand at the outset? Like are you seeing a lot of excitement demand with respect to this drug? Thanks.

嘿夥計們。感謝您提出我的問題。回到 Crinecerfont 的發布。你們在那裡表示你們將免費提供我們的藥物，不是嗎？在保險開始之前，也許只是幫助我們透過您的擴展安全擴展研究來了解目前正在使用免費藥物的患者數量，以及您如何關注吸收方面？您基本上會向每個來的人提供免費藥品嗎？您是否看到人們對這種藥物有很多興奮的需求？謝謝。

I’ll answer the piece about the long-term extension. But we do have long term extension programs going on, right now, globally in both pediatrics and adult patients. Two comments on that, first of all, I think its enabling us collect some longer term real word information about the patients. And that’s important. And secondly, the number of patients remaining in the program remains incredibly high, which -- with very, very dropouts. Which I think, again is indicative of the ongoing tolerability, safety, and excellent uptake with respect to Crinecerfont in this program.

我將回答長期延期的問題。但我們目前確實在全球範圍內針對兒科和成人患者開展長期推廣計劃。對此有兩點評論，首先，我認為它使我們能夠收集有關患者的一些長期真實資訊。這很重要。其次，留在該計劃中的患者數量仍然非常高，而且退出率非常非常高。我認為這再次表明了 Crinecerfont 在該計劃中持續的耐受性、安全性和良好的接受度。

Yeah, and with regards to the reimbursement dynamics, as I mentioned in my prepared remarks, the majority of the patients in the CAH community, are either commercially insured or from Medicaid. And many commercial insurance plans have policies in place that restrict reimbursement free drugs and/or have a new market blocks in place. And so the expectation is that even as we get patients started on therapy it's going to take some time to work through the reimbursement. So we are going to have a program in place that allows us to get patients started and that is really across both commercial and Medicaid.

是的，關於報銷動態，正如我在準備好的演講中提到的，CAH 社區的大多數患者要么有商業保險，要么有醫療補助。許多商業保險計劃都制定了限制免費藥物報銷的政策和/或製定了新的市場封鎖。因此，我們預計，即使我們讓患者開始接受治療，也需要一些時間來完成報銷。因此，我們將製定一個計劃，讓我們能夠讓患者開始，這實際上是跨商業和醫療補助的。

Ultimately we're confident in our ability to get patients started as indicated by our success with INGREZZA, the customer dynamics early in the INGREZZA launch. But ultimately we think that Crinecerfont offers a significant opportunity here for us to diversify our revenue and we think that ultimately creates a lot of value for the CAH community. So we'll have a lot more to talk about when we get closer to the launch in terms of our access strategy.

最終，我們對讓患者開始使用的能力充滿信心，正如我們在 INGREZZA 上的成功以及 INGREZZA 推出初期的客戶動態所表明的那樣。但最終我們認為 Crinecerfont 為我們提供了一個多元化收入的重要機會，我們認為這最終為 CAH 社群創造了許多價值。因此，當我們的訪問策略接近發佈時，我們將有更多的內容要討論。

Okay, Thank you.

好的，謝謝。

Thank you.

謝謝。

Ami Fadia, Needham & Company.

阿米法迪亞 (Ami Fadia)，李約瑟公司。

Hi, this is Buna on for Ami. Thank you for taking our question. So on NBI-’845, how do you see it fitting into the current treatment paradigm and what are the expectations from the upcoming FDA meeting? Thank you.

大家好，我是阿米的布納。感謝您提出我們的問題。那麼，對於 NBI-845，您認為它如何適應目前的治療模式以及對即將舉行的 FDA 會議有何期望？謝謝。

So in terms of the FDA meeting, we will be getting clarity on our Phase III strategy and that will enable us to start our Phase III program in the first half of next year. In terms of the indication or the area of focus in major depressive disorder the Phase II data that we generated was in the context of inadequate response to currently available treatments and then in that setting we anticipated this could either be an adjunctive treatment to other antidepressants currently in the field or as a standalone monotherapy and we'll be exploring both the treatment forward.

因此，就 FDA 會議而言，我們將明確我們的 III 期策略，這將使我們能夠在明年上半年啟動我們的 III 期計劃。就重度憂鬱症的適應症或重點領域而言，我們產生的II 期數據是在對目前可用治療反應不足的背景下進行的，然後在這種情況下，我們預計這可能是目前其他抗憂鬱藥的輔助治療在現場或作為獨立的單一療法，我們將繼續探索這兩種治療方法。

Thank you for your response.

感謝您的回覆。

Thank you and there are no further questions. At this time I'll turn the call back to Kyle for closing remarks.

謝謝您，沒有其他問題了。此時，我會將電話轉回凱爾，讓其結束語。

Thanks Ashley. So this morning we covered a great deal of ground. I'd like to close by reinforcing my opening message. Our exceptional leadership team and our energized organization are really positioning our kind of lead in neuroscience moving forward.

謝謝阿什利。所以今天早上我們討論了很多內容。最後，我想強調一下我的開場白。我們卓越的領導團隊和充滿活力的組織真正奠定了我們在神經科學領域的領先地位。

I'm certainly inspired by all work that’s ahead and ever more confident in our potential. You know today we touched on a lot of different things. We talked about a bit on our strategy, our pipeline and our promising commercial opportunities. If you think about this being my first earnings call, I'm hoping you take away two things from our opening remarks and our Q&A.

我當然受到所有未來工作的啟發，並且對我們的潛力更加充滿信心。你知道今天我們談了很多不同的事情。我們討論了一些關於我們的策略、我們的產品線和我們有前途的商業機會。如果您認為這是我的第一次財報電話會議，我希望您能從我們的開場白和問答中學到兩點。

One is our commitment to discovery, developing and commercializing innovative medicines and I think you've seen from our discussions that this comes with risks and requires time and investment. But I'm hoping that you also see that we're committed, equally committed to delivering near and long term value for our organization and our shareholders.

一是我們對發現、開發和商業化創新藥物的承諾，我想您從我們的討論中已經看到，這伴隨著風險，需要時間和投資。但我希望您也看到我們致力於為我們的組織和股東提供近期和長期價值。

So with that, I think that we'll close here today by saying that busy year end ahead for us all and we're looking forward to connecting with many of you virtually and in-person for those who will be attending some of the many healthcare conferences that remain here in the next couple of months.

因此，我想我們今天將在此結束，對我們所有人來說，忙碌的一年即將結束，我們期待著與你們中的許多人進行虛擬和麵對面的聯繫，以便那些將參加許多活動的人未來幾個月仍將在這裡舉行的醫療保健會議。

So with that, thanks again, for the call and looking forward to speaking with you soon.

因此，再次感謝您的來電，並期待盡快與您交談。

Thank you. And this does conclude today’s program. Thank for your participation. You may disconnect at any time.

謝謝。今天的節目到此結束。感謝您的參與。您可以隨時斷開連線。