Intra-Cellular Therapies Inc (ITCI) 2024 Q3 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Intra-Cellular Therapies 3Q 2024 Earnings Conference Call. (Operator Instructions). Please be advised that today's conference is being recorded.

美好的一天，感謝您的支持。歡迎參加細胞內療法 2024 年第三季收益電話會議。（操作員說明）。請注意，今天的會議正在錄製中。

I would now like to hand the call over to Juan Sanchez, Head of Investor Relations. Please go ahead.

我現在想將電話轉交給投資者關係主管胡安·桑切斯 (Juan Sanchez)。請繼續。

Good morning, and thank you all for joining us on our third quarter 2024 earnings call. Joining me on the call today are Dr. Sharon Mates, Chairman and Chief Executive Officer; Mark Neumann, Chief Commercial Officer; Dr. Suresh Durgam, Chief Medical Officer; and Sanjeev Narula, Chief Financial Officer. A slide deck to complement today's call is available under the Investor Events section of our corporate website.

早安，感謝大家參加我們的 2024 年第三季財報電話會議。今天與我一起參加電話會議的還有董事長兼執行長 Sharon Mates 博士；馬克‧諾伊曼，首席商務官； Suresh Durgam 博士，首席醫療官；和財務長桑吉夫·納魯拉 (Sanjeev Narula)。我們公司網站的投資者活動部分提供了補充今天電話會議的幻燈片。

During today's call, we will be making certain forward-looking statements. These forward-looking statements are based on current information, assumptions and expectations. Those statements are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements. These statements are made only as of the date of this conference call, and the company disclaims any obligation to update such statements.

在今天的電話會議中，我們將做出某些前瞻性聲明。這些前瞻性陳述是基於當前資訊、假設和預期。這些陳述可能會發生變化，並涉及許多風險和不確定性，可能導致實際結果與前瞻性陳述中包含的結果有重大差異。這些風險和其他風險在我們向美國證券交易委員會提交的定期文件（包括我們的季度和年度報告）中進行了描述。請您注意不要過度依賴這些前瞻性陳述。這些聲明僅截至本次電話會議之日作出，本公司不承擔更新此類聲明的義務。

I will now turn the call over to Sharon.

我現在將把電話轉給莎倫。

Thanks, Juan. Good morning, and welcome to our third quarter earnings call. We are pleased to share our Q3 results and to describe the exciting progress we have made across the company. CAPLYTA's growth trajectory continues to reflect a compelling product profile and our successful commercial execution with net sales of $175.2 million in the third quarter representing a 39% increase over the third quarter of 2023.

謝謝，胡安。早上好，歡迎參加我們的第三季財報電話會議。我們很高興分享我們第三季的業績，並描述我們在整個公司取得的令人興奮的進展。CAPLYTA 的成長軌跡繼續反映了引人注目的產品概況和我們成功的商業執行，第三季淨銷售額為 1.752 億美元，比 2023 年第三季成長了 39%。

Based on this continued strong performance, we are raising our 2024 full year net sales guidance range to $665 million to $685 million. We look forward to building a positive momentum for the rest of 2024 and beyond. In addition, we continue to advance our broad pipeline, and we are on track to submit our supplemental NDA for the adjunctive treatment of major depressive disorder or MDD this quarter. Looking at the big picture, our objective has always been to have the greatest number of patients.

基於持續強勁的業績表現，我們將 2024 年全年淨銷售額指引範圍提高至 6.65 億美元至 6.85 億美元。我們期待在 2024 年剩餘時間及以後建立積極的勢頭。此外，我們繼續推進我們廣泛的產品線，我們預計在本季度提交用於輔助治療重度憂鬱症或 MDD 的補充 NDA。從大局來看，我們的目標始終是擁有最多的患者。

We believe that the recent unprecedented efficacy and safety data for CAPLYTA in our MDD Phase 3 studies profoundly expands the impact CAPLYTA will have in the treatment of mood disorders. As we approach this major MDD approval milestone, we wanted to give you our perspective on the tremendous market opportunity that we see for CAPLYTA across the mood disorder spectrum and provide the rationale for our confidence.

我們相信，近期 MDD 3 期研究中 CAPLYTA 前所未有的療效和安全性數據大大擴展了 CAPLYTA 在治療情緒障礙方面的影響。當我們接近這項 MDD 批准的重要里程碑時，我們希望向您提供我們對 CAPLYTA 在情緒障礙領域所看到的巨大市場機會的看法，並為我們的信心提供理由。

First, as I noted, CAPLYTA's efficacy results in studies 501 and 502 for the adjunctive treatment of MDD are truly exceptional. This efficacy was confirmed in both studies, not only by the primary endpoint, the MADRS total score, but also by the strong results in the clinician-rated CGI-S scale and the patient-reported QIDS scale. This data further builds on the consistently strong efficacy data we have seen in our pivotal studies throughout our CAPLYTA development program.

首先，正如我所指出的，CAPLYTA 在研究 501 和 502 中對於 MDD 輔助治療的療效結果確實非常出色。這項功效在兩項研究中得到了證實，不僅透過主要終點 MADRS 總分，而且還透過臨床醫生評估的 CGI-S 量表和患者報告的 QIDS 量表的強勁結果得到證實。這些數據進一步建立在我們在整個 CAPLYTA 開發計畫的關鍵研究中所看到的一貫強大的功效數據的基礎上。

CAPLYTA's robust efficacy is complemented with a favorable safety and tolerability profile, including a favorable metabolic weight and movement disorder profile. Metabolic disturbances, weight gain and motor adverse events are major reasons why patients discontinue their treatment and often result in poor clinical outcomes. Another important feature of CAPLYTA's convenient dosing. CAPLYTA is dosed once a day with no need for titration with or without food, making it an attractive option for prescribers and patients. These are important attributes that become more critical as the medicine is used by broader patient populations.

CAPLYTA 的強大功效與良好的安全性和耐受性相輔相成，包括良好的代謝體重和運動障礙特徵。代謝紊亂、體重增加和運動不良事件是患者停止治療並常導致不良臨床結果的主要原因。CAPLYTA 方便給藥的另一個重要特性。CAPLYTA 每天給藥一次，無需在進食或空腹情況​​下進行滴定，這使其成為處方者和患者的一個有吸引力的選擇。隨著藥物被更廣泛的患者群體使用，這些重要屬性變得更加重要。

With this compelling profile, we are excited about CAPLYTA's potential for the treatment of MDD, a large market with unmet medical needs. There are over 21 million patients with MDD and antidepression therapies do not adequately address depressive symptoms in more than half the patients currently using them. There are a few drugs approved for the adjunctive treatment of MDD, and there is still a significant unmet need for efficacious, safe and well-tolerated medicines for these patients. As a result, we believe CAPLYTA is well positioned to become a drug of choice across the spectrum of major mood disorders.

憑藉這一令人信服的概況，我們對 CAPLYTA 治療 MDD 的潛力感到興奮，MDD 是一個醫療需求未滿足的龐大市場。有超過 2,100 萬名重度憂鬱症患者，目前使用抗憂鬱療法的患者中有一半以上無法充分解決憂鬱症狀。有一些藥物被批准用於 MDD 的輔助治療，但這些患者對有效、安全和耐受性良好的藥物的需求仍然顯著未得到滿足。因此，我們相信 CAPLYTA 完全有能力成為治療各種主要情緒障礙的首選藥物。

Starting with bipolar depression, CAPLYTA has the broadest label in this indication, which includes bipolar I and bipolar II patients and as monotherapy and as adjunctive therapy. In patients with mixed features and anxious distress difficult-to-treat patient phenotype, we have also reported robust positive clinical results. The potential addition of the adjunctive MDD indication not only adds a large patient population that can benefit from CAPLYTA but also gives prescribers additional confidence about the efficacy, safety and tolerability of the drug across multiple patient populations.

從雙相憂鬱症開始，CAPLYTA 在該適應症中擁有最廣泛的標籤，包括雙相 I 和雙相 II 患者以及作為單一療法和輔助治療。對於具有混合特徵和難以治療的焦慮困擾表型的患者，我們也報告了穩健的正面臨床結果。潛在增加的輔助 MDD 適應症不僅增加了可以從 CAPLYTA 中受益的大量患者群體，而且還使處方者對該藥物在多個患者群體中的療效、安全性和耐受性更有信心。

In our view, this positions CAPLYTA as a top-of-mind choice for prescribers when treating a broad spectrum of patients including patients with a diagnosis of bipolar I or bipolar II disorder or MDD. We have demonstrated our commercial expertise and have the financial resources we anticipate to be necessary to maximize CAPLYTA's full potential. Taking all this together, we believe CAPLYTA represents at least a $5 billion opportunity within the next 10 years. This reflects our expectation that CAPLYTA will become a leading treatment across a spectrum of mood disorders and is primarily driven by contributions from bipolar depression and MDD and to a lesser extent, schizophrenia.

我們認為，這使得 CAPLYTA 成為處方者在治療廣泛患者（包括診斷為 I 型雙相情感障礙或 II 型雙相情感障礙或 MDD 的患者）時的首要選擇。我們已經展示了我們的商業專業知識，並擁有我們預計充分發揮 CAPLYTA 潛力所需的財務資源。綜上所述，我們相信 CAPLYTA 在未來 10 年內至少代表著 50 億美元的機會。這反映了我們的預期，CAPLYTA 將成為一系列情緒障礙的領先治療方法，主要是由雙相憂鬱症和重度憂鬱症以及較小程度上的精神分裂症所推動的。

In addition to CAPLYTA, we have a very rich pipeline, which includes additional lumateperone programs as well as other novel programs. This will result in significant clinical milestones in the near and medium term. In terms of our lumateperone long-acting injectable program, we commenced clinical conduct in our Phase 1 single ascending dose study, evaluating four different formulations. Our objective is to develop formulations with treatment durations of one month or longer. And over the next year, we will be prioritizing the formulations with the best profile as we proceed with this Phase 1 study. Let me now touch on our ITI-1284 development programs, which we are very excited about.

除了 CAPLYTA 之外，我們還有非常豐富的產品線，其中包括額外的 lumateperone 專案以及其他新穎的專案。這將在近期和中期產生重大的臨床里程碑。就我們的lumateperone長效注射劑計畫而言，我們開始了1期單劑量遞增研究的臨床研究，評估了四種不同的製劑。我們的目標是開發治療持續時間為一個月或更長時間的製劑。在接下來的一年裡，我們將在進行第一階段研究時優先考慮具有最佳性能的配方。現在讓我談談我們非常興奮的 ITI-1284 開發計劃。

Patient enrollment is ongoing in our Phase 2 clinical trial evaluating 1284 in patients with generalized anxiety disorder, or GAD, as an adjunctive therapy to generalized anxiety medications. We believe GAD represents at least a $1 billion opportunity for ITI-1284. Currently, there are only five drugs approved for the treatment of GAD and only as monotherapy. Anxiety prevalence and severity is on the rise and recent reports suggest the prevalence of 20 million patients in the US with 13 million patients being treated. About half of patients who received treatment did not respond adequately to initial therapy.

我們的 2 期臨床試驗正在進行患者入組，評估 1284 名廣泛性焦慮症 (GAD) 患者作為廣泛性焦慮藥物的輔助療法。我們相信 GAD 為 ITI-1284 帶來了至少 10 億美元的機會。目前，只有五種藥物被批准用於治療廣泛性焦慮症，並且僅作為單一療法。焦慮的盛行率和嚴重程度正在上升，最近的報告顯示，美國有 2,000 萬名患者患有焦慮症，其中 1,300 萬名患者正在接受治療。大約一半接受治療的患者對初始治療沒有充分反應。

If approved, ITI-1284 would represent a new mechanism of action in the treatment of GAD and be the only drug approved for patients who have failed prior medications. We believe ITI-1284 is well suited for this patient population and may offer an effective, safe and well-tolerated treatment. Patient enrollment is ongoing in our ITI-1284 Phase 2 clinical study evaluating patients with psychosis associated with Alzheimer's disease. We are pleased to announce that we recently commenced patient enrollment in our Phase 2 program in patients with agitation in Alzheimer's disease.

如果獲得批准，ITI-1284將代表一種治療廣泛性焦慮症的新作用機制，並且是唯一被批准用於治療先前藥物治療失敗的患者的藥物。我們相信 ITI-1284 非常適合該患者群體，並且可以提供有效、安全且耐受性良好的治療。我們的 ITI-1284 2 期臨床研究正在進行患者入組，評估與阿茲海默症相關的精神病患者。我們很高興地宣布，我們最近開始針對患有阿茲海默症的躁動患者進行第二階段計畫的患者入組。

All of our ongoing Phase 2 studies with ITI-1284 are large and designed as potential registration studies. Continuing with our pipeline, our [len mis potent] Phase 2 clinical trial in Parkinson's disease is progressing, and we expect to complete this study by the end of 2025. ITI-1020, our second molecule in our PDE1 platform is being developed for certain cancers and cancer-related comorbidity. ITI-1020 is currently advancing through a Phase 1 single ascending dose study.

我們正在進行的所有 ITI-1284 2 期研究都是大型的，並且被設計為潛在的註冊研究。繼續我們的研發管線，我們針對帕金森氏症的 [lenmis effective] 2 期臨床試驗正在取得進展，我們預計在 2025 年底之前完成這項研究。ITI-1020 是我們 PDE1 平台中的第二個分子，正在開發用於某些癌症和癌症相關合併症。ITI-1020 目前正在推進第一期單劑量遞增研究。

Lastly, we are very excited about our 1,500 program, exemplified by ITI-1549, a non-homogenic neuroplastigen. We believe that ITI-1549 and holds great promise as the treatment of mood, anxiety and other disorders. ITI-1549 may offer a safe, effective medicine with a novel mechanism of action that can be conveniently administered without the risk associated with psychedelic hallucinogens. Earlier this year at the Society of Biological Psychiatry Annual Meeting and the recent Society for Neuroscience meeting, we presented results from our clinical work showing that ITI-1549 is non-hallucinogenic, provides improved social interactions, reverses anhedonia and decreases anxiety-like behaviors in animal models.

最後，我們對我們的 1,500 計劃感到非常興奮，例如 ITI-1549，一種非均質神經塑膠。我們相信 ITI-1549 在治療情緒、焦慮和其他疾病方面具有巨大的前景。ITI-1549 可以提供一種安全、有效的藥物，具有新穎的作用機制，可以方便地給藥，而沒有與致幻劑相關的風險。今年早些時候，在生物精神病學學會年會和最近的神經科學學會會議上，我們展示了我們的臨床工作結果，表明ITI-1549 不具有致幻性，可以改善社交互動，逆轉快感缺失並減少焦慮樣行為。

Preclinically, ITI-1549 has also been shown to enhance neuroplasticity by stimulating the mTOR signaling pathway in the prefrontal cortex and to increase in the right growth and complexity. ITI-1549 is completing IND-enabling studies and expected to enter human testing in 2025. In summary, we are very excited about our bright future. We are confident in our ability to capitalize on the substantial growth opportunities ahead. We have experienced high-performing teams, and we are in a strong financial position. I am proud of our accomplishments and look forward to building on this success. I'll now turn the call over to Mark to provide details on CAPLYTA's performance and commercial plans. Mark?

臨床前，ITI-1549 也被證明可以透過刺激前額葉皮質中的 mTOR 訊號通路來增強神經可塑性，並增加正確的生長和複雜性。ITI-1549 正在完成 IND 支持研究，預計 2025 年進入人體測試。總而言之，我們對光明的未來感到非常興奮。我們對利用未來巨大成長機會的能力充滿信心。我們擁有經驗豐富的高績效團隊，財務狀況強勁。我為我們的成就感到自豪，並期待在這一成功的基礎上再接再厲。我現在將把電話轉給 Mark，以提供有關 CAPLYTA 性能和商業計劃的詳細資訊。標記？

Thanks, Sharon, and good morning, everyone. CAPLYTA registered another strong performance in Q3 with robust year-over-year growth in total prescriptions of 38% and a sequential quarter-over-quarter growth rate of approximately 9%, demonstrating strong commercial execution as we overcame a traditionally slower quarter for the antipsychotic market due to summer seasonality factors. CAPLYTA's growth again outpaced both the branded antipsychotic market, which grew at 4% this quarter as well as the overall antipsychotic market, which grew at only 1%.

謝謝莎倫，大家早安。CAPLYTA 在第三季度再次表現強勁，總處方量同比強勁增長 38%，環比增長率約為 9%，顯示出強大的商業執行力，我們克服了抗精神病藥物傳統上較慢的季度市場受夏季季節性因素影響。CAPLYTA 的成長再次超過了本季成長 4% 的品牌抗精神病藥物市場以及僅成長 1% 的整體抗精神病藥物市場。

CAPLYTA's market-leading growth is being driven by its continued strong uptake in bipolar depression and is being sourced by significant increases in both the breadth of our prescriber base as well as an increase in the average depth of prescribing. During Q3, we added 4,000 new first-time prescribers of CAPLYTA, having now increased that cumulative total since launch to over 49,000 unique prescribers. We expect this strong growth trajectory to continue in the fourth quarter and throughout 2025 as we continue to invest to optimize the growth of CAPLYTA in bipolar depression.

CAPLYTA 市場領先的成長是由其在雙相憂鬱症方面的持續強勁增長所推動的，其根源在於我們的處方者基礎廣度的顯著增加以及處方平均深度的增加。在第三季度，我們新增了 4,000 名首次 CAPLYTA 處方者，自推出以來的累積總數現已增加到超過 49,000 名獨特處方者。我們預計這種強勁的成長軌跡將在第四季度和整個 2025 年持續下去，因為我們將繼續投資優化 CAPLYTA 在雙相憂鬱症中的成長。

To this end, we recently completed an expansion of our sales force during Q3, adding 150 new sales representatives to leverage the growing opportunity with primary care physicians in CAPLYTA's current indication. This new sales team is now in the field promoting cap later for bipolar depression in primary care offices. CAPLYTA's broad label, which includes both bipolar I and bipolar II depression, provides us with an opportunity to expand our reach and educational activities with primary care physicians as we have seen an increasing role of primary care in treating bipolar depression.

為此，我們最近在第三季完成了銷售團隊的擴張，增加了 150 名新的銷售代表，以利用 CAPLYTA 當前適應症中初級保健醫生不斷增長的機會。這個新的銷售團隊現在正在初級保健辦公室推廣雙相憂鬱症的上限。CAPLYTA 的廣泛標籤包括I 型雙相抑鬱症和II 型雙相抑鬱症，為我們提供了擴大我們與初級保健醫生的接觸範圍和教育活動的機會，因為我們已經看到初級保健在治療雙相抑鬱症中的作用越來越大。

Early feedback to the messaging has been highly positive as primary care physicians value CAPLYTA's compelling clinical profile of strong efficacy and favorable metabolic weight and movement disorder profile, coupled with convenient once-daily dosing with no titration. Primary care physicians view all of these product attributes to be beneficial in treating their patients with bipolar depression.

對這一消息的早期反饋非常積極，因為初級保健醫生重視CAPLYTA 令人信服的臨床特徵，即強大的功效、良好的代謝體重和運動障礙特徵，再加上方便的每日一次給藥，無需滴定。初級保健醫生認為所有這些產品特性對於治療雙相憂鬱症患者都是有益的。

It will take some time for this new sales team to be fully optimized in their territories, so while we expect to see some positive effect in the fourth quarter this year, we believe most of the impact will be realized in 2025 and beyond. We also continue to make substantial progress in our commercialization planning for a potential label expansion in major depressive disorder, which would increase our total addressable market for CAPLYTA from nearly 50% of antipsychotic prescriptions for schizophrenia and bipolar depression to nearly 80% with the addition of an MDD indication.

這個新的銷售團隊需要一段時間才能在其所在地區得到全面優化，因此，雖然我們預計在今年第四季會看到一些正面效果，但我們相信大部分影響將在 2025 年及以後實現。我們也繼續在重度憂鬱症潛在標籤擴展的商業化計劃方面取得實質進展，這將使我們的CAPLYTA 總潛在市場從精神分裂症和雙相憂鬱症抗精神病藥物處方的近50% 增加到近80 %，此外MDD 指示。

We believe the robust results in studies 501 and 502 will position CAPLYTA as a leading option in the adjunctive treatment of MDD. And coupled with our existing data in bipolar depression, we will look to establish CAPLYTA as the first choice treatment across mood disorders. There are more than 30 million adult patients in the US with either bipolar depression or major depressive disorder representing large medical conditions. The substantial growth in the bipolar depression market and the strong uptake of recent new drug launches in MDD, both speak to the important unmet medical needs for efficacious safe and well-tolerated treatment in both patient populations.

我們相信研究 501 和 502 的穩健結果將使 CAPLYTA 成為 MDD 輔助治療的領先選擇。結合我們現有的雙極性憂鬱數據，我們將尋求將 CAPLYTA 確立為治療情緒障礙的首選療法。美國有超過 3000 萬成年患者患有雙相憂鬱症或重度憂鬱症，這些疾病代表嚴重的醫療狀況。雙相憂鬱症市場的大幅成長以及最近推出的重度憂鬱症新藥的強勁成長，都顯示這兩個患者群體對有效、安全和耐受性良好的治療的重要醫療需求尚未得到滿足。

We believe CAPLYTA will play a leading role in addressing these needs. Our recently completed expansion provide the opportunity to promote CAPLYTA in bipolar depression to primary care physicians and allows these prescribers gain familiarity with CAPLYTA to use and enhanced brand awareness ahead of a potential label expansion in MDD. To fully optimize the launch in MDD, a second primary care sales force expansion is planned for 2025 and in connection with the potential approval of CAPLYTA, the adjunctive treatment of MDD. We will share more details of those plans at the appropriate time next year.

我們相信 CAPLYTA 將在滿足這些需求方面發揮主導作用。我們最近完成的擴展為初級保健醫生提供了在雙相抑鬱症中推廣 CAPLYTA 的機會，並允許這些處方醫生在 MDD 的潛在標籤擴展之前熟悉 CAPLYTA 的使用並提高品牌知名度。為了充分優化 MDD 的上市，計劃於 2025 年進行第二次初級保健銷售隊伍擴張，並與 MDD 輔助治療 CAPLYTA 的潛在批准相關。我們將在明年適當的時候分享這些計劃的更多細節。

In summary, we believe we are well positioned to drive consistent growth of CAPLYTA and to maximize the significant opportunities ahead of us in the coming years. We look forward to continuing to update you on the successful launch of CAPLYTA.

總之，我們相信我們有能力推動 CAPLYTA 的持續成長，並在未來幾年最大限度地利用我們面前的重大機會。我們期待繼續向您通報 CAPLYTA 成功推出的最新情況。

I'll now turn the call over to Sanjeev to further discuss our financial performance. Sanjeev?

我現在將把電話轉給桑吉夫，進一步討論我們的財務表現。桑吉夫？

Thank you, Mark, and good morning, everyone. Great to be with you today to share my thoughts on the recent quarter and our full year expectations.

謝謝你，馬克，大家早安。很高興今天與您分享我對最近一個季度和全年預期的想法。

First, I'd like to start off by saying how honored I am to have joined the Intra-Cellular Therapies leadership team as Chief Financial Officer. I'm thrilled to be part of the company during this exciting time of growth. Since I began in August, I've been meeting with colleagues across the company, and I'm impressed with the high caliber of our talent.

首先，我首先想說的是，我非常榮幸能夠加入細胞內療法領導團隊並擔任財務長。我很高興能在這個令人興奮的發展時期成為公司的一員。自從我八月入職以來，我一直在與公司各地的同事會面，我們的人才的高素質給我留下了深刻的印象。

I believe we have the right strategy to grow CAPLYTA in its approved indications and look forward to the potential launch in MDD next year as well as advancing our robust pipeline. I'm confident in our strong fundamentals and the company's growth potential. I consider it a privilege to partner with Sharon and the rest of our management team to continue to create significant shareholder value.

我相信我們有正確的策略來發展 CAPLYTA 的批准適應症，並期待明年在 MDD 的潛在上市以及推進我們強大的產品線。我對我們強勁的基本面和公司的成長潛力充滿信心。我認為很榮幸能夠與莎倫和我們管理團隊的其他成員合作，繼續創造顯著的股東價值。

Our third quarter results represent another strong quarter in CAPLYTA's growth trajectory. As Sharon mentioned, CAPLYTA's net product sales increased to $175.2 million, representing 39% growth versus the same period in 2023. Our net sales grew 9% sequentially versus Q2 2024 primarily driven by increased prescription demand. Our gross to net percentage in the quarter was in mid-30s, consistent with our expectations.

我們的第三季業績代表了 CAPLYTA 成長軌蹟的另一個強勁季度。正如 Sharon 所提到的，CAPLYTA 的產品淨銷售額增至 1.752 億美元，較 2023 年同期成長 39%。與 2024 年第二季相比，我們的淨銷售額較上季成長了 9%，這主要是由於處方需求增加所致。本季我們的毛淨百分比在 30 左右，與我們的預期一致。

Selling, general administrative expenses for the third quarter were $132.1 million compared to $105.2 million for the same period in 2023. The increase was mainly a result of the primary care sales force expansion as well as increase in the marketing, advertising and channel administrative expenses to support the company's growth.

第三季的銷售和一般管理費用為 1.321 億美元，而 2023 年同期為 1.052 億美元。這一成長主要是由於初級保健銷售隊伍的擴張以及為支持公司成長而增加的行銷、廣告和通路管理費用的結果。

Our R&D expenses were $66.8 million compared to $41.6 million for the same period in 2023. Our pipeline continues to advance. In the third quarter, R&D expenses increased primarily due to activities associated with lumateperone and other clinical programs. Specifically, the initiation of our Phase 3 bipolar mania studies, our Phase 3 pediatric program as well as our ITI 1284 Phase 2 studies in GAD and psychosis nagitation studies in Alzheimer disease. Now let me say a few words on Q4 and full year guidance ranges.

我們的研發費用為 6,680 萬美元，而 2023 年同期為 4,160 萬美元。我們的管道繼續推進。第三季度，研發費用增加主要是因為與魯美哌隆和其他臨床項目相關的活動。具體來說，啟動了我們的雙相躁症第 3 期研究、兒科計畫第 3 期以及 GAD 的 ITI 1284 第 2 期研究和阿茲海默症的精神病導航研究。現在讓我談談第四季和全年指引範圍。

We expect net product sales momentum to continue, driven by strong prescription demand. We expect our gross to net percentage to remain in mid-30s for the fourth quarter. As a result, we're raising our capital at a net product sales guidance range to $665 million to $685 million for 2024. Given the year-to-date spend at this time, we're narrowing our full year SG&A expense guidance range to $490 million to $510 million, and our full year R&D guidance range to $220 million to $230 million.

我們預計，在強勁的處方需求的推動下，淨產品銷售動能將持續下去。我們預計第四季度的毛淨百分比將保持在 30 左右。因此，我們將在 2024 年將淨產品銷售指引範圍的資本提高到 6.65 億美元至 6.85 億美元。考慮到今年迄今的支出，我們將全年 SG&A 支出指引縮小至 4.9 億至 5.1 億美元，並將全年研發指導範圍縮小至 2.2 億至 2.3 億美元。

Finally, our financial position remains strong. Cash and investments totaled $1 billion on September 30, 2024, compared to $499.7 million on December 31, 2023. To recap, our business from Nemelka sound, we're ending the year with a positive momentum with a strong balance sheet, we believe we are well positioned to maximize capitalizes potential and continue to invest in our pipeline program.

最後，我們的財務狀況依然強勁。截至 2024 年 9 月 30 日，現金及投資總額為 10 億美元，而 2023 年 12 月 31 日為 4.997 億美元。回顧一下，我們內梅爾卡的業務表現良好，我們將以強勁的資產負債表和積極的勢頭結束今年，我們相信我們處於有利位置，可以最大限度地發揮資本潛力，並繼續投資於我們的管道計劃。

This concludes our prepared remarks. I'd like to hand it back to the operator to open the line for your questions.

我們準備好的演講到此結束。我想將其交還給接線員，以便為您解答問題。

(Operator Instructions) Andrew Tsai, Jefferies.

（操作員說明）Andrew Tsai，Jefferies。

Congrats on the quarter and the strong execution. My question is around your sales opportunity comment for CAPLYTA, $5 billion. over the next 10 years. So are you thinking a fairly equal sales mix between MDD and bipolar -- are you expecting MDD sales to be meaningfully larger than bioplar and just bigger picture, is it fair to assume you're expecting CAPLYTA ultimately to be prescribed more than the rest of these other antipsychotics out there, the branded ones at least?

恭喜本季的業績和強勁的執行力。我的問題是關於您對 CAPLYTA 50 億美元銷售機會的評論。未來10年。那麼，您是否認為MDD 和雙相情感障礙之間的銷售組合相當平等- 您是否期望MDD 銷售額明顯大於雙相情感障礙，並且從更大的角度來看，可以公平地假設您期望CAPLYTA 最終比其他藥物處方更多還有其他抗精神病藥物嗎，至少是品牌藥？

So thanks for the question, Andrew. And thanks for the kind words in the intro to your question. Maybe, Mark, would you like to address the question?

謝謝你的提問，安德魯。感謝您在問題介紹中的客氣話。也許，馬克，你想回答這個問題嗎？

Yes, sure. Thanks for the question, Andrew. To reiterate, at least at a high level, Sharon's comments in our prepared remarks, what the forecast reflects is really our confidence that CAPLYTA will become a leading treatment option across mood disorders across bipolar I, bipolar II and MDD. And the forecast is primarily driven by bipolar depression and MDD and to a much lesser extent, schizophrenia, which continues to grow nicely, but is the least of the three indications.

是的，當然。謝謝你的提問，安德魯。至少在高水準上重申Sharon 在我們準備好的發言中的評論，預測所反映的實際上是我們的信心，即CAPLYTA 將成為治療I 型雙相情感障礙、II 型雙相情感障礙和MDD 情緒障礙的領先治療選擇。這項預測主要是由​​雙相憂鬱症和重度憂鬱症以及較小程度的精神分裂症推動的，精神分裂症繼續良好增長，但在這三個適應症中是最少的。

To give you a little additional color for bipolar depression, we see CAPLYTA continuing on its current growth trajectory, which leads to significant market share gains over time, and CAPLYTA becomes one of the leading treatments in bipolar depression. For MDD, we recently conducted some rigorous quantitative market research, which confirms our belief that studies 501 and 502 represent a best-in-class profile for CAPLYTA and we believe that will lead to a market-leading share among the branded antipsychotics. So to your question, Andrew, both bipolar depression and MDD contribute very significantly to the overall estimate that we have of achieving $5 billion within 10 years.

為了讓您對雙相憂鬱症有更多了解，我們看到CAPLYTA 繼續保持當前的成長軌跡，隨著時間的推移，這將帶來顯著的市場份額成長，並且CAPLYTA 成為雙相憂鬱症的領先治療方法之一。對於 MDD，我們最近進行了一些嚴格的定量市場研究，這證實了我們的信念，即研究 501 和 502 代表了 CAPLYTA 的同類最佳概況，我們相信這將導致品牌抗精神病藥物中的市場領先份額。因此，對於你的問題，安德魯，雙相憂鬱症和重度憂鬱症對我們在 10 年內實現 50 億美元目標的總體估計做出了非常重要的貢獻。

Jessica Fye, J.P. Morgan.

潔西卡法伊，摩根大通。

Following up on the prior question. Can you just touch on what prompted you to unveil this $5 billion long-term target for CAPLYTA now? And then I have a follow-on.

繼續之前的問題。您能否簡單談談是什麼促使您現在公佈 CAPLYTA 50 億美元的長期目標？然後我有一個後續。

Thanks for the question, Jessica. I'll start, and then I'll ask Mark or Sanjeev if they want to chime in. As you know, we are continuously being asked by the Street, what the market opportunity is for both CAPLYTA and drugs in our pipeline. Just as early on, we did not give revenue guidance. We think as we mature, it is time for us to be giving you our internal forecast as we refine them too and as we get the confidence in the potential for what we've been finding in all of our market research and all of our internal forecasting. Mark, do you want to add anything to that?

謝謝你的提問，潔西卡。我先開始，然後我會問馬克或桑吉夫是否願意插話。如您所知，華爾街不斷詢問我們 CAPLYTA 和我們正在研發的藥物的市場機會是什麼。正如早些時候，我們沒有給出收入指引。我們認為，隨著我們的成熟，現在是時候向您提供我們的內部預測了，因為我們也在完善它們，並且我們對我們在所有市場研究和所有內部研究中發現的潛力充滿信心。馬克，你想補充什麼嗎？

No, I think that's exactly it, Sharon. I think we've always believed in the potential of CAPLYTA in certainly in the near term but also the long term. I think when we saw the results of Studies 501 and 502, we were certainly impressed by the very robust efficacy and favorable safety and tolerability profile in MDD. And now we've had a chance to do some rigorous quantitative market research, which confirmed our impressions of what that profile represented. And I think it's just all of that added to the confidence that we have about the long-term potential of CAPLYTA.

不，我想就是這樣，莎倫。我認為我們始終相信 CAPLYTA 的潛力，無論是在短期或長期。我認為，當我們看到研究 501 和 502 的結果時，我們肯定對 MDD 的強大療效以及良好的安全性和耐受性印象深刻。現在我們有機會進行一些嚴格的定量市場研究，這證實了我們對該概況所代表的印象。我認為這一切都增強了我們對 CAPLYTA 長期潛力的信心。

And I think also with the increase now with the launch of our primary care dedicated sales force, I think gives us even further confidence. And these drugs are being prescribed more and more in the primary care setting as well as not only by physicians but by nurse practitioners and PAs, et cetera, in the mood disorders. So we think that all of this builds on the confidence to support these numbers.

我認為，隨著我們初級保健專業銷售團隊的推出，現在的成長也給了我們更大的信心。這些藥物越來越多地在初級保健機構中使用，不僅由醫生使用，而且還由執業護士和私人護理人員等在治療情緒障礙時使用。因此，我們認為這一切都建立在支持這些數字的信心之上。

Okay. And then just one quick follow-up on the pipeline. Curious if you could just speak to how enrollment is going in the Phase 2 AD study for 1284. Is there any chance we could see the anxiety data for 1284 next year?

好的。然後對管道進行快速跟進。很好奇您能否談談 1284 年第二階段 AD 研究的註冊進展。明年我們有機會看到1284的焦慮數據嗎？

Well, I'd never say never. But typically, one doesn't do their projections based on enrollment speeding up to your projections based on enrollment, either being status quo or slowing down. So I think that we stick by the guidance we've given to date and if next year something changes, we can let you know about that.

好吧，我永遠不會說永遠不會。但通常情況下，人們不會根據招生速度進行預測，而是根據招生情況進行預測，要么維持現狀，要么放慢速度。因此，我認為我們會堅持迄今為止給予的指導，如果明年有什麼變化，我們可以讓您知道。

Charles Duncan, Cantor.

查爾斯鄧肯，康托爾。

Congrats on the quarter, very nice performance. And I'd like hearing the substance behind the $5 billion vision I had a question really on pipeline. When you consider LAI and what other companies are being challenged with LAI, how important is that for the luma franchise versus, say, 1,284, et cetera, in terms of the vision longer term? And then you have a lot of pipeline candidates. Could you tell us what you're most excited about? It's a little simplistic, but let me know what your thoughts are.

恭喜這個季度，表現非常好。我想聽聽 50 億美元願景背後的實質內容，我確實有一個關於管道的問題。當您考慮 LAI 以及其他面臨 LAI 挑戰的公司時，從長期願景來看，這對於 luma 特許經營權與 1,284 等公司相比有多重要？然後你就有很多候選管道。可以告訴我們你最興奮的是什麼嗎？雖然有點簡單，但請告訴我您的想法。

Okay. Charles, thanks for the kind words. I'll start and then I'll ask if Suresh wants to chime in. On the LAI, we started the development of LAIs for patients to have another option. As you know, we're now testing four different formulations.

好的。查爾斯，謝謝你的客氣話。我先開始，然後問蘇雷什願不願意插話。在LAI上，我們開始開發LAI，讓患者有另一種選擇。如您所知，我們現在正在測試四種不同的配方。

And as I mentioned in our prepared remarks that that study is ongoing and throughout next year, we will have further data as we're basically pitting these different formulations against each other, and we'll be looking at the safety, the tolerability at the PK values. And certain ones will drop out we anticipate. I think that it is separate and apart from our CAPLYTA franchise, which we continue to see as growing very substantially over time. And we're very excited about it.

正如我在我們準備好的發言中提到的那樣，這項研究正在進行中，整個明年，我們將獲得進一步的數據，因為我們基本上是在將這些不同的配方相互比較，我們將研究其安全性和耐受性。我們預計某些人會退出。我認為它是獨立於我們的 CAPLYTA 特許經營權的，我們認為隨著時間的推移，我們的 CAPLYTA 特許經營權將大幅增長。我們對此感到非常興奮。

As for 1,284, that again, is a separate pipeline right now. And I think that we're very excited about GAD is a huge opportunity, and we think that we would really be paving the way for drugs with new mechanisms in GAD and really, we look forward to seeing that data. As to which -- what do I like best or what do we like best, it's really, really hard to say in one-on-one meetings I say that's like asking you which child of yours do you like the best.

至於 1,284，現在又是一個單獨的管道。我認為我們對 GAD 是一個巨大的機會感到非常興奮，我們認為我們真的會為具有 GAD 新機制的藥物鋪平道路，我們真的期待看到這些數據。至於我最喜歡什麼或我們最喜歡什麼，在一對一的會議上真的很難說，我說這就像問你最喜歡你的哪個孩子一樣。

I think -- we'll continue to look. We're a science-driven company, and we'll continue to look at the science and we'll continue to look at the data. And assuming the data is good for each clinical trials we'll continue to progress. If the data, there's some pickups in data as we go forward, those programs may get called. So we'll let the science drive us and the data is always the most important thing to help guide you in your development of these programs.

我想——我們會繼續尋找。我們是一家科學驅動的公司，我們將繼續專注於科學，我們將繼續關注數據。假設每個臨床試驗的數據都良好，我們將繼續取得進展。如果資料隨著我們的進展而出現一些資料增加，那麼這些程式可能會被呼叫。因此，我們將讓科學驅動我們，數據始終是幫助指導您開發這些程式的最重要的東西。

Jason Gerberry, Bank of America Securities.

Jason Gerberry，美國銀行證券公司。

Mine is around the guide. If I look at the midpoint, it implies that the annual growth rate steps up in fourth quarter, close to think high 40% versus 39% growth rate year-on-year in 3Q. So as I think about that acceleration in growth, I'm wondering if you can kind of just flag the tailwinds there. Is the sales force expansion? Is this getting some uptake in Unipolar MDD or mixed features or just something else? I appreciate it.

我的在指南周圍。如果我看中點，這意味著第四季的年增長率將上升，接近想像中的 40%，而第三季的年成長率為 39%。因此，當我想到增長的加速時，我想知道你是否可以標記出那裡的順風車。銷售團隊是否擴大？這是單極 MDD 或混合功能或其他功能得到一些採用嗎？我很感激。

Sanjeev?

桑吉夫？

Yes. Yes. So Jason, thank you for the question. So Jason, we had -- as you saw a strong quarter, right, 9% quarter-over-quarter growth on a quarter which typically has seasonality of summer. And then we outperformed the market, in general, as Mark pointed out, if you look at the antipsychotic market, on the branded antipsychotic, which grew 4% and the overall antipsychotic market grew 1%, and we grew 9%. So that momentum continues with us.

是的。是的。傑森，謝謝你的提問。所以傑森，正如您所看到的，我們有一個強勁的季度，對吧，在通常具有夏季季節性的季度中，季度環比增長了 9%。然後，正如馬克指出的那樣，總的來說，我們的表現優於市場，如果你看看抗精神病藥物市場，品牌抗精神病藥物增長了4%，整體抗精神病藥物市場增長了1%，而我們增長了9%。因此，我們將繼續保持這種勢頭。

So what we expect Q4 generally stronger, and that's why we expect that -- and then also, even though primary field force is just being operational in the field, probably we'll see most impact in 2025. We do expect some impact of that in the fourth quarter. So if you take the midpoint, Jason, we expect to grow a little -- if you take the midpoint, we expect to grow sequentially 11%. So from a 9% to 11%, I think it's pretty reasonable, and we're confident about our guide from that perspective.

因此，我們預計第四季度總體會更強，這就是我們預期的原因 - 而且，即使主要現場部隊剛剛在現場運作，我們可能會在 2025 年看到最大的影響。我們確實預計第四季會產生一些影響。所以，傑森，如果你取中點，我們預計會成長一點——如果你取中點，我們預計會環比成長 11%。所以從 9% 到 11%，我認為這是相當合理的，從這個角度來看，我們對我們的指南充滿信心。

Jeff Hung, Morgan Stanley.

傑夫洪，摩根士丹利。

Congratulations on the progress. Following up on the LAI program, what are your expectations on demand for that formulation? And what proportion of patients might be interested in long-acting lumateperone versus the current dosing? And then I have a follow-up.

祝賀取得的進展。繼 LAI 計劃之後，您對該配方的需求有何期望？與目前的劑量相比，有多少比例的患者可能對長效魯美哌隆感興趣？然後我有一個後續行動。

Yes. This is Sharon. Thanks for the question. I think it's a little too soon to tell. Again, we're going to be driven by the data. We do not expect the to have a huge impact. And presently, depending on whose numbers you want to look at in schizophrenia. the percent penetration is anywhere from 5% to the highest number I've ever seen is 10%, but usually, it's about 8% has the highest number. So I think that we don't really expect there to be any impact on our oral franchise.

是的。這是莎倫。謝謝你的提問。我認為現在說還為時過早。同樣，我們將由數據驅動。我們預計不會產生巨大影響。目前，取決於您想查看哪些人的精神分裂症數據。滲透率從 5% 到我見過的最高數字 10% 不等，但通常情況下，最高數字約為 8%。所以我認為我們並不真正期望這會對我們的口頭特許經營產生任何影響。

I would like to just remind you that given the safety and tolerability of CAPLYTA. We really think that patients like taking an oral compound very much. And so we really don't see much impact there. We will be updating you as we go forward on what we see with these different formulations, and we'll let you know.

我想提醒您的是，考慮到 CAPLYTA 的安全性和耐受性。我們確實認為患者非常喜歡服用口服化合物。所以我們確實沒有看到太大的影響。隨著我們對這些不同配方的觀察，我們將及時向您通報最新情況，並讓您知道。

Great. That's very helpful. And then maybe quickly, you indicated that additional results from the Phase 3 MDD studies will be shared at upcoming conferences. Are you presenting data at ACNP. And if so, what new aspects of the 501, 502 data might you be sharing with the medical community.

偉大的。這非常有幫助。然後也許很快，您表示將在即將舉行的會議上分享第 3 階段 MDD 研究的其他結果。您是否在 ACNP 上展示數據？如果是這樣，您可能會與醫學界分享 501、502 數據的哪些新方面。

Suresh, do you want to take that?

蘇雷什，你想接受嗎？

Yes. Yes. We are going to be presenting at ACNP different aspects of the studies, both 501, 502 and also the open-label study the 503. So all that will be included. And also the data that was not released only we talked about top line results. We'll be talking about the secondary endpoints, additional post-sales will be presented at the meeting.

是的。是的。我們將在 ACNP 上展示研究的不同方面，包括 501、502 以及開放標籤研究 503。所以所有這些都將包括在內。還有未發布的數據，我們僅討論了頂線結果。我們將討論次要端點，額外的售後將在會議上介紹。

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。

This is [Devin], on for Brian. Congrats on a great quarter. Just have a couple of questions on the peak sales guide that you've provided. So in regards to that, how are you kind of thinking about what the shape of the shape of the shape of the MDD expansion could look like post approval there? And would the Vraylar launch and MDD perhaps a good comparison? Or do you believe you could potentially bend the curve even more given the efficacy and safety profile of CAPLYTA that's been shown?

我是[德文]，由布萊恩接聽。恭喜您度過了一個出色的季度。只是對您提供的峰值銷售指南有幾個問題。那麼就此而言，您如何看待 MDD 擴充的形狀在獲得批准後會是什麼樣子？Vraylar 發布和 MDD 可能是一個很好的比較？或者您認為考慮到 CAPLYTA 已顯示的功效和安全性，您可能會進一步彎曲曲線？

And then are you also seeing any early effects of the recent KarXT launch into schizophrenia? And do you anticipate that there might be any share erosion that could occur as that launch progresses?

那麼您是否也看到了最近推出的 KarXT 對精神分裂症的任何早期影響？您是否預計隨著發布的進行，可能會出現份額侵蝕？

Mark, do you want to take that?

馬克，你想接受這個嗎？

Yes, sure, Devin. Let me start with your second question. with the launch of the KarXT product. We haven't seen a lot out there yet. It's too early to see the prescription data coming through. Our understanding is that they're launching this week. We don't expect a significant impact on CAPLYTA of that launch.

是的，當然，德文。讓我從你的第二個問題開始。隨著 KarXT 產品的推出。我們還沒有看到很多。現在查看處方數據還為時過早。我們的理解是他們將於本週推出。我們預計該發布不會對 CAPLYTA 產生重大影響。

Certainly, it's good for patients. Any new launches are good for patients, especially in schizophrenia. But schizophrenia is a market that has the switching dynamic where patients are really dissatisfied with existing antipsychotics typically on the safety and tolerability side, which is where CAPLYTA has really had its gains in schizophrenia. So we don't see any one product dominating that schizophrenia market.

當然，這對患者來說是有好處的。任何新產品的推出都對患者有利，尤其是精神分裂症患者。但精神分裂症是一個不斷變化的市場，患者對現有的抗精神病藥物確實不滿意，通常是在安全性和耐受性方面，而這正是 CAPLYTA 在精神分裂症方面真正獲益的地方。因此，我們沒有看到任何一種產品主導精神分裂症市場。

And secondly, as we've talked about in our prepared remarks and some of the questions, the long-term potential for CAPLYTA is really in the mood disorders. That's where we're going to see the real significant potential across bipolar I, bipolar I and MDD, and we don't see the KarXT product competing there. So we don't see a big impact there. As far as the shape of the MDD curve, yes, we -- again, with the market research that we did, we do expect a rapid uptake in MDD.

其次，正如我們在準備好的演講和一些問題中談到的，CAPLYTA 的長期潛力確實在於情緒障礙。這就是我們將看到雙極 I、雙極 I 和 MDD 真正巨大潛力的地方，但我們看不到 KarXT 產品在那裡競爭。所以我們沒有看到很大的影響。就 MDD 曲線的形狀而言，是的，我們再次透過我們所做的市場研究，確實預期 MDD 會迅速普及。

If you look at the analogs in the past, both our own and the sort of stick inflection that we saw when we got the bipolar depression indication. We would expect at least a similar type of uptake MDD given the profile that came out of 501, 502, and this is consistent with other antipsychotics that have added mood disorder indications like bipolar depression and more recently, MDD with Vraylar.

如果你看看過去的類似情況，無論是我們自己的還是我們在獲得雙相憂鬱症跡象時看到的那種棒狀變化。考慮到 501、502 的概況，我們預計至少會出現類似類型的 MDD，這與其他增加了情緒障礙適應症的抗精神病藥物（如雙相抑鬱症）以及最近的 Vraylar 的 MDD 是一致的。

And we think that the success that Vraylar has had in the marketplace with MDD really reflects what was our belief all along that there still remains a very significant unmet medical need for a product with robust efficacy, which was delivered in 501 and 502 with a favorable safety and tolerability profile, which we replicated in MDD, a similar profile that we saw in bipolar depression and so on schizophrenia, and with the addition of a convenient dosing regimen, once a day without regard to food, and the physician can start the patient as an effective dose and not have to titrate them up. So all of those things taken together, we think, will lead to a rapid uptake in MDD and supports the overall guidance that we've provided on the $5 billion opportunity.

我們認為，Vraylar 在MDD 市場上取得的成功確實反映了我們一直以來的信念，即對於具有強大功效的產品，仍然存在非常重大的未滿足的醫療需求，該產品在501 和502 中交付，並獲得了良好的評估我們在MDD 中複製了安全性和耐受性概況，與我們在雙相抑鬱症等精神分裂症中看到的類似概況，並且增加了方便的給藥方案，每天一次，不考慮食物，醫生可以開始給患者用藥作為有效劑量，而不必滴定它們。因此，我們認為，所有這些因素加在一起將導致 MDD 的快速普及，並支持我們為 50 億美元機會提供的整體指導。

Michael DiFiore, Evercore ISI.

邁克爾·迪菲奧裡，Evercore ISI。

Congrats on such great progress during the quarter. Two quick ones from me. Number one, are there any incremental updates regarding your plans for pursuing anxious distressed indications separately. And I know you could only offer limited comments now, but regarding the planned primary sales force expansion in 2025, could you share whether it will match or exceed the recent 150-representative increase? And additionally, are there any specific geographic regions targeted for this expansion?

恭喜本季取得如此巨大的進步。我的兩個快的。第一，關於您單獨追求焦慮困擾跡象的計劃是否有任何增量更新。我知道您現在只能提供有限的評論，但關於計劃在 2025 年擴大主要銷售隊伍，您能否分享一下是否會匹配或超過最近 150 名代表的增長？此外，此次擴張是否有特定的地理區域？

Great. So I'll ask Suresh to address the anxious distress and maybe what you can do is define anxious distress and talk about how the DSM addresses anxious distress, and then Mark, if you could address question on the sales force.

偉大的。因此，我將請 Suresh 解決焦慮困擾，也許您可以定義焦慮困擾並討論 DSM 如何解決焦慮困擾，然後馬克，您是否可以解決有關銷售人員的問題。

Yes. In terms of the anxious distress that is a specifier that was added into the DSM-5. And we have looked anxious patients within slightly different of having who has MDD, major depressive disorder, or bipolar disorder in the [mode] disorder space have symptoms of anxiety and there are five symptoms that have classified of those fights symptoms that they have at least two symptoms of anxiety that is considered anxious distress. And also, there is a rating for severity having 3, 4, or 5 as the severity increases. We have looked at these patients in our studies, both in our bipolar mixed future study the 403 study, where we looked at patients with bipolar depression with mixed features and anxious distress.

是的。就焦慮困擾而言，這是 DSM-5 中添加的說明符。我們發現，焦慮症患者與患有憂鬱症、重度憂鬱症或躁鬱症的人略有不同，他們有焦慮症狀，並且有五種症狀將他們至少有的這些症狀分類為被認為是焦慮困擾的兩種焦慮症狀。而且，隨著嚴重性的增加，嚴重性的評級為 3、4 或 5。我們在研究中觀察了這些患者，在我們的雙相混合未來研究 403 研究中，我們觀察了具有混合特徵和焦慮困擾的雙相憂鬱症患者。

We also looked at the MDD population in that also having mixed features and anxious distress. And we have shared the data were that it was robust in both these populations of MDD with anxious distress as well as bipolar anxious distress. We also looked at further in our agent MDD program, and we have seen good results in that, and we will be presenting that data in our next conference. This is also important because anxious dissipations are difficult to treat. They have higher comorbidities and also have higher suicidal path -- suicidality, both in terms of [third parts] and suicidal ideations.

我們也研究了重度憂鬱症族群，他們也具有混合特徵和焦慮困擾。我們分享的數據表明，它在患有焦慮困擾和雙相焦慮困擾的 MDD 群體中都很有效。我們還進一步研究了我們的代理 MDD 計劃，我們已經看到了良好的結果，我們將在下一次會議上展示這些數據。這也很重要，因為焦慮性放蕩很難治療。他們有較高的合併症，也有較高的自殺路徑－自殺傾向，無論是在[第三部分]或自殺意念方面。

So this is also important in terms of treating the patient, knowing that the patients who are the clinicians offices if they have anxious distress comorbid with MDD that the option that for lumateperone is able to help those patients. This is in terms of our -- what anxious distress is.

因此，這對於治療患者而言也很重要，因為臨床醫生辦公室的患者如果患有焦慮症並伴有 MDD，那麼 Lumateperone 的選擇能夠幫助這些患者。這就是我們的焦慮困擾。

So I'll update you on this program further as we get further along and as we start presenting all of this data. So then if we could go to the second part of your question on sales force expansion, Mark?

因此，當我們取得進一步進展並開始展示所有這些數據時，我將進一步向您介紹該計劃。那麼，馬克，我們是否可以討論您關於銷售隊伍擴張問題的第二部分？

Yes, sure. Mike, regarding further sales force expansion next year, we will provide you more details in later calls. What I would say is our current sales force stands at about 530, and we will be expanding that further. And I will say the early feedback on the messaging to primary care physicians in bipolar depression, with CAPLYTA is really resonating. The profile of strong efficacy, favorable safety and tolerability and especially the single dose once daily dosing that the primary care physicians can start the patient at the effective dose and not have to titrate up is something that they really see as beneficial in treating their patients.

是的，當然。麥克，關於明年進一步擴大銷售隊伍的問題，我們將在稍後的電話中向您提供更多詳細資訊。我想說的是，我們目前的銷售人員約為 530 人，我們將進一步擴大這一規模。我想說的是，CAPLYTA 向雙相憂鬱症初級保健醫生傳達的訊息的早期回饋確實引起了共鳴。強大的功效、良好的安全性和耐受性，特別是每天一次的單劑量給藥，初級保健醫生可以以有效劑量開始給患者治療，而不必逐步增加劑量，他們認為這對治療患者確實有益。

So the early feedback on our expansion into primary care is that the message is resonating very well. Now looking to the future, we're also very excited, as we've said about the commercial opportunity of the potential label expansion in MDD, and we will look to invest behind the brand at a level that will optimize that launch and the growth prospects that we have for the brand. So as we've done in the past, we'll share more details of those efforts and that expansion at the appropriate time next year.

因此，關於我們擴展到初級保健領域的早期回饋是，這一訊息引起了很好的共鳴。現在展望未來，我們也非常興奮，正如我們所說的 MDD 潛在標籤擴張的商業機會，我們將尋求在品牌背後進行投資，以優化該品牌的推出和增長我們對該品牌的前景。因此，正如我們過去所做的那樣，我們將在明年適當的時候分享這些努力和擴張的更多細節。

(Operator Instructions) Marc Goodman, Leerink Partners.

（操作員說明）Marc Goodman，Leerink Partners。

This is Basma, on for Marc. We had a question regarding the 1,284. Can you elaborate a little bit more on the differentiation of 1284 from CAPLYTA. We were actually wondering whether the created formulation yielded further improvement on the safety profile especially with regard to somnolence rate.

這是巴斯馬，替補的是馬克。我們有一個關於 1,284 的問題。您能詳細說明一下 1284 與 CAPLYTA 的差異嗎？我們實際上想知道所創建的配方是否能進一步改善安全性，特別是在嗜睡率方面。

Especially what? I'm sorry, I missed the last part of your question.

特別是什麼？抱歉，我錯過了你問題的最後一部分。

With regards to somnolence rate.

關於嗜睡率。

Yes. Okay. I'll start and ask rest wants to add anything. So yes, we are very excited about the 1284 program in several different indications, and we will have even further indications as we progress with these programs.

是的。好的。我會開始詢問休息是否需要添加任何內容。所以，是的，我們對 1284 計劃的幾種不同適應症感到非常興奮，隨著這些計劃的進展，我們將獲得更多適應症。

We did a Phase 1 study in normal healthy volunteers and in one cohort of elderly volunteers. And we did see the safety profile is very good. And in fact, you hit what we saw in the elderly population, especially is decrease in the somnolence. Now it's a small patient population, and we're looking at whether that continues in these larger studies, but we're very excited about that.

我們對正常健康志願者和一群老年志願者進行了一項第一階段研究。我們確實看到安全狀況非常好。事實上，你看到了我們在老年人口中看到的情況，特別是嗜睡的減少。現在患者群體很小，我們正在研究是否會在這些更大規模的研究中繼續下去，但我們對此感到非常興奮。

And to remind you, the duterated form expresses more of the parent than lumateperone. And so we are looking to explore the meaning of that in terms of both -- really in terms of efficacy in terms of where we go with that, if it's in the dosing is whether it's in the indication that are extremely difficult to treat patients, et cetera. So we're looking at all of that.

提醒您的是，雙聯形式比 lumateperone 更能表達母體。因此，我們正在尋求探索這兩個方面的意義——實際上是在功效方面，在我們的治療方向方面，如果是劑量方面，是否是在極難治療患者的適應症方面，等等。所以我們正在研究所有這些。

Suresh, did you want to add anything?

蘇雷什，你想補充什麼嗎？

No, nothing for this, Sharon.

不，沒什麼，莎倫。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Another question on 1284 specifically on your GAD program. Wondering what kind of market research you've done on the extent to which atypical antipsychotics are used specifically for GAD, what is the level of prescriptions that we generally see for a typical in this setting, whether it's monotherapy or adjunctive therapy.

1284 上的另一個問題專門針對您的 GAD 計劃。想知道您對非典型抗精神病藥物專門用於治療廣泛性焦慮症的程度進行了什麼樣的市場研究，我們通常在這種情況下看到的典型處方水平是多少，無論是單一療法還是輔助療法。

And as you look at that opportunity, is your goal here is essentially to expand the overall antipsychotic footprint by offering a product with a differentiated profile? I guess how are you thinking about this in terms of share gains versus market expansion?

當您看到這個機會時，您的目標是否本質上是透過提供具有差異化特徵的產品來擴大整體抗精神病藥物的足跡？我想您如何看待市佔率收益與市​​場擴張之間的關係？

Thanks for the question. Mark, do you want to start and then either Suresh or I will chime in afterwards.

謝謝你的提問。馬克，你想開始嗎？

Yes, sure, David. In the research that we've been doing and as we've been looking at the GAD market, we actually see a lot of similarities with how the antipsychotic market evolved in you have a condition that's highly prevalent, about 20 million patients a year. Most of them get first-line therapy that does not adequately treat their disease.

是的，當然，大衛。在我們一直在進行的研究以及對廣泛性焦慮症市場的關注中，我們實際上看到了與抗精神病藥物市場的演變有很多相似之處，因為這種疾病非常普遍，每年約有 2000 萬患者。他們中的大多數人接受的一線治療並不能充分治療他們的疾病。

And even though there are no antipsychotics currently approved in GAD, there is some off-label use what you tend to see is GAD many times is comorbid with other mental health conditions like depression, like bipolar depression and other things. And so you're dealing with a patient that has both a depressive disorder as well as an anxiety disorder. And so adjunctive use of an antipsychotic is something that I think physicians probably see similar to how they would use an antipsychotic in treating MDD adjunctively.

儘管目前還沒有批准治療廣泛性焦慮症的抗精神病藥物，但還是有一些標籤外用途，您通常會看到廣泛性焦慮症很多時候與抑鬱症、雙相抑鬱症等其他精神健康狀況並存。因此，您面對的是一位同時患有憂鬱症和焦慮症的患者。因此，我認為醫生可能會認為輔助使用抗精神病藥物與使用抗精神病藥物輔助治療重度憂鬱症類似。

Now certainly, there is also patients with GAD as their only condition. The penetration of antipsychotics into that segment is less because there's no antipsychotics currently approved for that. So I think we believe that with good clinical results in GAD for 1284. This is a large market. It's a market that we think we could penetrate well both in the patient with comortmage conditions, but also in the patient that is suffering from GAD alone.

當然，現在也有一些患者將廣泛性焦慮症視為唯一的病症。抗精神病藥物在該領域的滲透率較低，因為目前還沒有批准用於該領域的抗精神病藥物。所以我認為我們相信 1284 在 GAD 方面具有良好的臨床效果。這是一個很大的市場。我們認為我們可以很好地滲透到這個市場，既可以滲透到患有併發症的患者中，也可以滲透到僅患有廣泛性焦慮症的患者中。

So maybe I'll stop there and ask if Suresh or Sharon, do you have any further comments on that.

所以也許我會就此打住，問問 Suresh 或 Sharon，你們對此還有什麼進一步的評論嗎？

I don't, but maybe Suresh, do you have any comments on the drugs that are being used now and what our opportunity is.

我不知道，但也許蘇雷什，您對現在使用的藥物以及我們的機會有什麼評論嗎？

Yes. In terms of the GAD, the current drugs that are approved are very limited in terms of -- or mainly SSRIs and SNRIs. There are only five drugs that are approved for in -- for long-term use, that is duloxetine, that is Cymbalta, Effexor, Paxil, and Lexapro. And also, we have the BuSpar medication that was approved. And we have the benzos for short term, but we cannot use them for long term. All these are apples first-line therapies. So we see an unmet need in patients who do not respond to these medications.

是的。就GAD而言，目前核准的藥物非常有限，或主要是SSRIs和SNRIs。只有五種藥物被批准長期使用，即度洛西汀、Cymbalta、Effexor、Paxil 和 Lexapro。而且，我們還有獲得批准的 BuSpar 藥物。我們有短期使用的苯並類藥物，但我們不能長期使用它們。所有這些都是蘋果的一線療法。因此，我們發現對這些藥物沒有反應的患者的需求未被滿足。

And similar as Mark was mentioning, that people prescribers are prescribing antipsychotics for patients who do not respond -- and this will be similar to what we have seen with MDD, where initial data of MDD adjunctive treatment was added on. So we see similarities there. And also from the mechanism of the 1284 and safety profile, we believe that this will be a good opportunity to pursue this indication and also have the patients with patients who do not respond to initial therapies.

與 Mark 提到的類似，處方醫生會為沒有反應的患者開出抗精神病藥物，這與我們在 MDD 中看到的情況類似，其中添加了 MDD 輔助治療的初始數據。所以我們看到了相似之處。而且從 1284 的機制和安全性來看，我們相信這將是一個很好的機會來追求這種適應症，並且也有對初始治療沒有反應的患者。

As in our bipolar program where we had a study that was a monotherapy program and another clinical study program that was adjunctive use. We are following a similar path in GAD. So right now, we have ongoing the adjunctive treatment. And very importantly, we will begin study therapy.

就像在我們的雙相情感障礙項目中一樣，我們有一項研究是單一治療項目，另一項臨床研究項目是輔助使用。我們在 GAD 中也遵循類似的路徑。所以現在我們正在進行輔助治療。非常重要的是，我們將開始研究治療。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

On the expectation of CAPLYTA reaching $5 billion in sales, what kind of changes in pricing over time are built into that projection?

CAPLYTA 銷售額預計將達到 50 億美元，隨著時間的推移，該預測中的定價會發生什麼樣的變化？

Mark, do you want to address that for Sanjeev? You're not sure? Yes.

馬克，你想為桑吉夫解決這個問題嗎？你不確定嗎？是的。

I can start and Sanjeev, if he has anything you'd like to add. We've assumed moderate improvement in net selling price over time, which incorporates our expectations of the potential impact of our IRA over time. So that's how I would characterize the pricing assumptions that we've used for that forecast.

我可以開始，桑吉夫，如果你有什麼要補充的。我們假設隨著時間的推移，淨售價將適度改善，其中包含我們對 IRA 隨著時間的推移的潛在影響的預期。這就是我如何描述我們用於該預測的定價假設的特徵。

Okay. I think that's what we have. Do we have any more questions?

好的。我想這就是我們所擁有的。我們還有什麼問題嗎？

We do have additional questions.

我們還有其他問題。

Okay. I think we have time for one or two more.

好的。我想我們還有時間再聊一兩個。

Corinne Jenkins, Goldman Sachs.

科琳·詹金斯，高盛。

Maybe from -- can you just talk a little bit about the sales force expansion kind of post next year? Do you think you'll be pretty rightsized for MDD at that point? Or will -- should we anticipate kind of like continued sales force expansion over the coming years. Maybe just talk a little bit about like your philosophy around how you think about the sales force size relative to the market opportunity.

也許是──你能談談明年的銷售隊伍擴張嗎？您認為那時您的規模是否適合 MDD？或者我們是否會預期未來幾年銷售隊伍會持續擴張。也許只是談談您如何看待相對於市場機會的銷售人員規模的理念。

Mark?

標記？

Yes, Karen. Our expectation is once we complete the expansion next year, which will take us further into primary care, predominantly, we will be rightsized to optimize the launch and the growth prospects that we have for CAPLYTA.

是的，凱倫。我們的期望是，一旦明年完成擴張，這將使我們進一步進入初級保健領域，我們將進行規模調整，以優化 CAPLYTA 的推出和成長前景。

Over time, you always re-evaluate that and any market conditions that might change. We'll constantly reevaluate that, but we expect that the expansion next year will get us where we need to be, which is highly competitive with a product profile that the market research suggests is a best-in-class profile. And we think that will be a combination that will allow us to maximize the opportunity that we have in MDD.

隨著時間的推移，您總是會重新評估這一點以及可能發生變化的任何市場條件。我們將不斷重新評估這一點，但我們預計明年的擴張將使我們達到我們需要的目標，這與市場研究表明的一流產品配置相比具有高度競爭力。我們認為，這種結合將使我們能夠最大限度地利用 MDD 中的機會。

Graig Suvannavejh, Mizuho Securities.

Graig Suvannavejh，瑞穗證券。

I was just very curious about the 1284 program and your comments around the Phase 2 studies as you've designed them as being registrational. And so the question is assuming positive data in one or all perhaps even of those studies, what are you currently contemplating for the regulatory strategy and next steps in order to secure approval? In other words, are there more trials that are likely? Or could these be the trials that support an SND -- or I'm sorry, an NDA? Thanks.

我只是對 1284 計劃以及您對第二階段研究的評論感到非常好奇，因為您將它們設計為註冊性的。因此，問題是假設其中一項或全部研究（甚至可能是其中一項研究）提供積極數據，您目前正在考慮什麼監管策略和後續步驟以確保獲得批准？換句話說，是否可能進行更多試驗？或者這些可能是支持 SND 的試驗——或者抱歉，是 NDA？謝謝。

Yes. So I think that the one that is where the regulatory pathway is extremely clear is in GAD or it is the clearest, I should say. And so assuming that studies are positive, we would go and discuss with the FDA then being the efficacy studies that are required for our for our filing.

是的。因此，我認為監管途徑極為明確的是 GAD，或者說是最明確的。因此，假設研究是積極的，我們將去與 FDA 討論，然後進行我們備案所需的功效研究。

And then, of course, we'll have rollover safety -- long-term safety studies as well. And so I think that program is very clear. On the other indications, I think it's a little too early on the Alzheimer indications. It's a little too early to say anything. But we will update you on that as we get further into next year.

當然，我們也會進行側翻安全性──以及長期安全性研究。所以我認為這個計劃非常明確。在其他適應症方面，我認為現在就阿茲海默症適應症來說還為時過早。現在說什麼都有點太早了。但隨著明年的進一步深入，我們將向您通報最新情況。

And I would now like to turn the call back to Sharon Mates for closing remarks.

現在我想將電話轉回給莎朗·馬茨（Sharon Mates），讓其致閉幕詞。

So thanks, everybody, for joining today. As you can see, I think we are very pleased with the progress we've made. We're very pleased with the performance of CAPLYTA and our ability to help patients. I want to just remind everybody that how we started this journey is to help patients and to expand the population of patients that we can help. So I think that we are advancing on our mission, and we look forward to continuing to do that and to updating you on our progress. And with that, operator, you can disconnect the call.

謝謝大家今天的加入。正如您所看到的，我認為我們對所取得的進展感到非常滿意。我們對 CAPLYTA 的表現以及我們幫助患者的能力感到非常滿意。我想提醒大家，我們開始這趟旅程的目的是幫助患者並擴大我們可以幫助的患者群體。因此，我認為我們正在履行我們的使命，我們期待繼續這樣做並向您通報我們的進展。這樣，接線員，您就可以掛斷電話了。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。