Axsome Therapeutics Inc (AXSM) 2023 Q1 法說會逐字稿

Hello, and welcome to the Axsome Therapeutics First Quarter 2023 Financial Results Conference Call and webcast. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Axsome Therapeutics 2023 年第一季度財務業績電話會議和網絡廣播。 （操作員指示）謹此提醒，本次會議正在錄製中。

It's now my pleasure to turn the call over to Mark Jacobson. Please go ahead, Mark.

現在我很高興將電話轉給馬克·雅各布森。請繼續，馬克。

Thank you, operator. Good morning, and thank you all for joining us on today's conference call. This morning, we issued our earnings press release providing a corporate update and details of the company's financial results for the first quarter of 2023. The release crossed the wire a short time ago and is available on our website at axsome.com.

謝謝你，接線員。早上好，感謝大家參加今天的電話會議。今天早上，我們發布了收益新聞稿，提供了公司最新動態以及公司 2023 年第一季度財務業績的詳細信息。該新聞稿不久前發布，可在我們的網站 axsome.com 上獲取。

During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety and intended utilization of our investigational agents, our clinical and nonclinical plans, our plans to present or report additional data, the anticipated conduct in the source of future clinical trials, regulatory plans, future research and development plans, our commercial plans regarding Sunosi, Auvelity and our pipeline products, revenue projections and possible intended use of cash and investments.

在今天的電話會議中，我們將做出某些前瞻性聲明。這些聲明可能包括有關我們研究藥物的功效、安全性和預期用途、我們的臨床和非臨床計劃、我們提供或報告額外數據的計劃、未來臨床試驗來源中的預期行為、監管等方面的聲明。計劃、未來的研發計劃、我們有關 Sunosi、Auvelity 和我們的管道產品的商業計劃、收入預測以及現金和投資的可能預期用途。

These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve 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, which are only made as of today's date, and the company disclaims any obligation to update such statements.

這些前瞻性陳述基於當前信息、假設和預期，這些信息、假設和預期可能會發生變化，並涉及可能導致實際結果與前瞻性陳述中包含的結果存在重大差異的風險和不確定性。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中進行了描述，包括我們的季度和年度報告。請您注意不要過分依賴這些前瞻性陳述，這些陳述僅在今天發布，並且公司不承擔更新此類陳述的任何義務。

Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; and Lori Englebert, Executive Vice President of Commercial and Business Development.

今天與我一起參加電話會議的還有首席執行官 Herriot Tabuteau 博士；尼克·皮齊，首席財務官；以及商業和業務發展執行副總裁 Lori Englebert。

Herriot will provide an overview of the company and progress made in the first quarter of 2023 as well as upcoming milestones. Following Herriot, Nick will review our financial results, and then Lori will provide a commercial update. We will then open the line for questions. Questions will be taken in the order they are received.

Herriot 將介紹公司概況、2023 年第一季度取得的進展以及即將到來的里程碑。赫里奧特之後，尼克將審查我們的財務業績，然後洛里將提供商業更新。然後我們將開通提問熱線。問題將按照收到的順序進行處理。

And with that, I will turn the call over to Herriot.

接下來，我會將電話轉給赫里奧特。

Thank you, Mark. Good morning, everyone, and thank you for joining Axsome Therapeutics First quarter 2023 Financial Results and Business Update Conference Call.

謝謝你，馬克。大家早上好，感謝您參加 Axsome Therapeutics 2023 年第一季度財務業績和業務更新電話會議。

We saw strong performance in all areas of our business in the first quarter, which included advancing the commercialization of Auvelity and Sunosi, progressing our late-stage product pipeline, out-licensing ex U.S. rights for Sunosi and strengthening our financial position.

第一季度我們在所有業務領域都取得了強勁的業績，其中包括推進 Auvelity 和 Sunosi 的商業化、推進我們的後期產品管道、轉讓 Sunosi 在美國的權利以及增強我們的財務狀況。

Total net product sales in the quarter were $28.8 million, driven by strong performance for Auvelity and solid performance for Sunosi. Based on the current prescription trends, we are pleased that our 2 marketed products are now helping a growing number of patients living with depression and with excessive daytime steepness.

本季度產品淨銷售額總額為 2,880 萬美元，這得益於 Auvelity 的強勁業績和 Sunosi 的穩健業績。根據當前的處方趨勢，我們很高興我們的兩種上市產品正在幫助越來越多的抑鬱症患者和白天過度陡峭的患者。

Later in the call, we will provide further details on our commercial performance for Auvelity and Sunosi.

稍後在電話會議中，我們將提供有關 Auvelity 和 Sunosi 商業表現的更多詳細信息。

The first quarter was an important milestone for Axsome as it was the first full quarter of sales for Auvelity. We have also had control of the U.S. rights to Sunosi for about 1 year. Earlier in the quarter, we announced the out-licensing of our ex U.S. marketing rights for Sunosi in Europe, the Middle East and North Africa to Pharmanovia. Pharmanovia shares our excitement and commitment to maximize the potential of Sunosi for patients worldwide.

第一季度對於 Axsome 來說是一個重要的里程碑，因為這是 Auvelity 的第一個完整季度的銷售額。我們還控制了 Sunosi 在美國的權利約一年。本季度早些時候，我們宣布將 Sunosi 在歐洲、中東和北非的美國前營銷權許可給 Pharmanovia。 Pharmanovia 與我們一樣興奮並致力於為全球患者最大限度地發揮 Sunosi 的潛力。

We continue to see significant potential for Sunosi, both in the current indications as well as in potential new indications. With regards to new indications, we remain on track to initiate a Phase III trial of solriamfetol, the active molecule in Sunosi in ADHD in adults in the second quarter.

我們繼續看到 Sunosi 在當前適應症和潛在新適應症方面的巨大潛力。關於新的適應症，我們仍有望在第二季度啟動 solriamfetol 的 III 期試驗，solriamfetol 是 Sunosi 治療成人 ADHD 的活性分子。

In addition to solriamfetol for ADHD, the rest of our leading CNS pipeline includes AXS-07 for migraine, AXS-12 for narcolepsy, AXS-14 for fibromyalgia and AXS-05 for Alzheimer's disease agitation and for smoking cessation. AXS-07, our developmental candidate for the acute treatment of migraine, manufacturing activities are moving forward to enable the resubmission of this NDA, which is slated for the second half of this year.

除了用於治療 ADHD 的 solriamfetol 之外，我們領先的 CNS 產品線的其餘部分還包括用於治療偏頭痛的 AXS-07、用於治療發作性睡病的 AXS-12、用於治療纖維肌痛的 AXS-14 以及用於治療阿爾茨海默病躁動和戒菸的 AXS-05。 AXS-07 是我們用於急性偏頭痛治療的候選藥物，其生產活動正在推進，以便能夠重新提交該新藥申請，該新藥定於今年下半年提交。

With AXS-12, our product candidate for the treatment of narcolepsy, we continue to expect top line results from the pivotal Phase III SYMPHONY trial in the first half of this year. With AXS-14, our product candidate for the treatment of fibromyalgia manufacturing and other activities related to preparations for the planned submission of an NDA are continuing, and we expect to be in a position to submit the NDA for this product candidate in the second half of this year.

對於我們用於治療發作性睡病的候選產品 AXS-12，我們繼續期待今年上半年關鍵的 III 期 SYMPHONY 試驗的頂線結果。通過 AXS-14，我們用於治療纖維肌痛的候選產品製造以及與計劃提交 NDA 準備工作相關的其他活動仍在繼續，我們預計能夠在下半年提交該候選產品的 NDA今年的。

With regards to AXS-05 for the treatment of Alzheimer's disease agitation, enrollment in the Phase III, ADVANCE-2 trial is progressing, and we anticipate completing this trial in the first half of 2024.

關於AXS-05用於治療阿爾茨海默病躁動症，III期ADVANCE-2試驗的入組工作正在進行中，我們預計在2024年上半年完成該試驗。

In addition, we plan to initiate a Phase II/III trial of AXS-05 in smoking cessation in the fourth quarter of 2023. In sum, we expect the next 12 to 18 months to be eventful as we drive the commercialization of Auvelity and Sunosi and as we advance our research and development pipeline.

此外，我們計劃於 2023 年第四季度啟動 AXS-05 戒菸 II/III 期試驗。總之，我們預計未來 12 至 18 個月將是多事之秋，因為我們將推動 Auvelity 和 Sunosi 的商業化以及我們推進我們的研發渠道。

I will now turn the call over to Nick, who will provide details of our financial performance.

我現在將把電話轉給尼克，他將提供我們財務業績的詳細信息。

Thank you, Herriot, and good morning. Today, I will discuss our first quarter results and provide some financial guidance.

謝謝你，赫里奧特，早上好。今天，我將討論我們第一季度的業績並提供一些財務指導。

Total revenue in the first quarter of 2023 was $94.6 million, consisting of net sales of our 2 commercialized products, Auvelity and Sunosi. The revenue from the Sunosi Europe and MENA out-licensing agreement signed with Pharmanovia and royalty revenue from Sunosi sales recorded by Pharmanovia.

2023 年第一季度的總收入為 9460 萬美元，包括我們的兩種商業化產品 Auvelity 和 Sunosi 的淨銷售額。來自 Sunosi Europe 和 MENA 與 Pharmanovia 簽署的外包許可協議的收入以及 Pharmanovia 記錄的 Sunosi 銷售的特許權使用費收入。

Auvelity net sales in the first quarter were $15.7 million. There were no net sales in the comparable period. Sunosi revenue for the quarter was $13.2 million. U.S. Sunosi sales were $11.2 million. International Sunosi revenue was $2 million, including approximately $300,000 in royalty revenue from Sunosi sales in the out-license markets.

Auvelity 第一季度淨銷售額為 1570 萬美元。比較期間沒有淨銷售額。 Sunosi 該季度的收入為 1320 萬美元。美國 Sunosi 銷售額為 1120 萬美元。 Sunosi 國際收入為 200 萬美元，其中包括來自 Sunosi 對外許可市場銷售的約 30 萬美元特許權使用費收入。

As a reminder, there was a change in the distribution model during the quarter, which negatively impacted Sunosi net sales by an estimated $3.3 million. There were no net revenues in the comparable period for Sunosi.

需要提醒的是，本季度分銷模式發生了變化，這對 Sunosi 淨銷售額產生了約 330 萬美元的負面影響。 Sunosi 同期沒有淨收入。

Cost of revenue was $7.6 million in the first quarter compared to none in the prior year. In addition to the manufacturing cost for Auvelity and Sunosi, cost of revenue includes a onetime charge of $5 million in licensing, sharing fees from the upfront payment received in the first quarter. Therefore, cost of revenue, excluding this onetime charge, was approximately $2.6 million.

第一季度的收入成本為 760 萬美元，而去年同期則為零。除了 Auvelity 和 Sunosi 的製造成本之外，收入成本還包括一次性 500 萬美元的許可費用，以及第一季度收到的預付款的分攤費用。因此，除去這筆一次性費用，收入成本約為 260 萬美元。

Research and development expenses were $17.8 million for the first quarter versus $12.6 million for the comparable period in 2022. The increase was primarily related to higher personnel costs associated with supporting the ongoing clinical trials, post-marketing commitments for Sunosi and Auvelity and noncash stock compensation expense.

第一季度的研發費用為 1780 萬美元，而 2022 年同期為 1260 萬美元。這一增長主要與支持正在進行的臨床試驗、Sunosi 和 Auvelity 的上市後承諾以及非現金股票補償相關的人員成本增加有關費用。

Selling, general and administrative expenses were $74.2 million for the first quarter versus $25.7 million for the comparable period in 2022. The increase was primarily related to commercial activities for Auvelity and Sunosi and higher noncash stock compensation expense due to the build-out of both commercial teams.

第一季度的銷售、一般和管理費用為 7420 萬美元，而 2022 年同期為 2570 萬美元。這一增長主要與 Auvelity 和 Sunosi 的商業活動以及由於兩家商業公司的擴建而導致的非現金股票補償費用增加有關。團隊。

Net loss for the first quarter was $11.2 million or $0.26 per share compared to a net loss of $39.6 million or $1.03 per share for the comparable period in 2022. The decrease in net loss for the first quarter versus the comparable period was primarily due to product sales from Auvelity and Sunosi, offset by higher selling, general and administrative expenses related to these commercial activities and license revenue received from Pharmanovia.

第一季度淨虧損為 1120 萬美元，即每股 0.26 美元，而 2022 年同期淨虧損為 3960 萬美元，即每股 1.03 美元。第一季度淨虧損較去年同期減少的主要原因是產品Auvelity 和 Sunosi 的銷售額，被與這些商業活動相關的較高銷售、一般和管理費用以及從 Pharmanovia 獲得的許可收入所抵消。

We ended the quarter with $246.5 million in cash and cash equivalents compared to $200.8 million as of year-end. During the first quarter, we did not utilize our ATM facility. In January of 2023, we amended our loan agreement with Hercules Capital to increase the size of the facility to $350 million to reduce the interest rate and to extend the maturity in interest-only periods, while accessing a $55 million tranche.

截至本季度末，我們的現金和現金等價物為 2.465 億美元，而截至年底為 2.008 億美元。第一季度，我們沒有使用 ATM 設施。 2023 年 1 月，我們修改了與 Hercules Capital 的貸款協議，將貸款規模增加至 3.5 億美元，以降低利率並延長只還息期的期限，同時獲得 5500 萬美元的貸款。

We believe that our current cash balance, along with the remaining committed capital from the $350 million term loan facility with Hercules Capital, is sufficient to fund anticipated operations into cash flow positivity based on our current operating plan.

我們相信，我們當前的現金餘額，以及來自 Hercules Capital 的 3.5 億美元定期貸款融資的剩余承諾資本，足以為根據我們當前運營計劃實現現金流量正值的預期運營提供資金。

I will now turn the call over to Lori, who will provide a commercial update.

我現在將把電話轉給洛里，她將提供商業更新。

Thank you, Nick, and good morning, everyone. We are off to a great start for 2023 and Q1 marked another exciting quarter for Axsome, with continued commercial growth for both Auvelity and Sunosi. We are pleased with the early metrics on Auvelity, which all point to a strong launch with significant long-term potential and with how the relaunch efforts on Sunosi are progressing.

謝謝你，尼克，大家早上好。我們在 2023 年有了一個良好的開端，第一季度標誌著 Axsome 又一個激動人心的季度，Auvelity 和 Sunosi 的商業持續增長。我們對 Auvelity 的早期指標感到滿意，這些指標都表明其推出具有巨大的長期潛力，並且對 Sunosi 的重新推出工作的進展情況感到滿意。

I will share key metrics from our commercial efforts for both brands, starting with Auvelity, followed by Sunosi. The end of Q1 represents the first full quarter of sales for Auvelity and only 5 full months post launch. We are still early in the launch, but remain highly encouraged by the consistent feedback from patients and HCPs.

我將分享我們為這兩個品牌所做的商業努力的關鍵指標，首先是 Auvelity，其次是 Sunosi。第一季度末代表了 Auvelity 的第一個完整季度的銷售額，並且距離發布僅 5 個月。我們仍處於啟動初期，但患者和 HCP 的一致反饋仍然令我們深受鼓舞。

Approximately 31,000 prescriptions were reported in Q1 for Auvelity, representing a growth of 298% in Q1 versus Q4. We saw prescription growth accelerate through increased depth with our early HCP adopters as well as increased breadth of new prescribers. At the end of Q1, Auvelity's prescriber base grew to over 6,000 unique HCP writers versus 2,200 unique HCPs at the end of Q4.

Auvelity 第一季度報告了約 31,000 個處方，較第四季度增長了 298%。我們看到，通過增加早期 HCP 採用者的深度以及增加新處方者的廣度，處方增長加速。第一季度末，Auvelity 的處方者基礎增長到超過 6,000 名獨特的 HCP 撰稿人，而第四季度末只有 2,200 名獨特的 HCP。

HCPs wrote prescriptions for over 15,000 new patients in Q1, bringing the total number of unique patients on Auvelity to over 21,000 at the end of Q1 versus 6,000 at the end of Q4. Our highly experiential sales force continues to drive adoption by educating HCPs on the product profile of Auvelity, through high-impact engagements, such as detailing and speaker programs, our sales force reached over 22,000 HCPs since launch.

第一季度，HCP 為超過 15,000 名新患者開了處方，使 Auvelity 的獨特患者總數在第一季度末達到 21,000 多名，而第四季度末為 6,000 名。我們經驗豐富的銷售團隊繼續通過對 HCP 進行 Auvelity 產品簡介教育來推動採用，通過高影響力的參與（例如詳細介紹和演講者計劃），自推出以來，我們的銷售團隊覆蓋了超過 22,000 名 HCP。

With regard to payer coverage, coverage for Auvelity across all channels is currently approximately 65% of all covered buys. In the commercial channel, which is expected to be the primary channel for Auvelity, coverage is now at approximately 40% of covered lives, and we look forward to additional formulary decisions in the coming months.

在付款人覆蓋範圍方面，目前 Auvelity 所有渠道的覆蓋範圍約為所有覆蓋購買的 65%。在商業渠道中，預計將成為 Auvelity 的主要渠道，目前覆蓋率約為覆蓋生活的 40%，我們期待在未來幾個月內做出更多的規定決定。

In the Medicaid and Medicare channels, approximately 100% of lives are now covered. Overall, payer coverage for Auvelity is proceeding as expected during the standard 6 to 9 months post-launch period and we expect additional formulary decisions in the coming months. We remain pleased and extremely encouraged by the initial launch progress and are steadfast and our commitment to our launch focus of driving HCP adoption, empowering patients and enabling quality access.

在醫療補助和醫療保險渠道中，目前大約 100% 的人的生命得到了保障。總體而言，Auvelity 的付款人覆蓋範圍在發布後標準的 6 至 9 個月內按預期進行，我們預計未來幾個月將做出更多規定決定。我們對最初的啟動進展感到高興和深受鼓舞，並堅定不移地致力於推動 HCP 的採用、為患者賦權和實現高質量的訪問。

Major depressive disorder, or MDD, is highly prevalent in a major public health concern with a mental health crisis that the U.S. is currently facing. 21 million adults were diagnosed in 2020, and there is a reported significant increase in prevalence as a result of the pandemic. Auvelity is an important new therapeutic option for patients living with this chronic and devastating conditions and we are proud of our efforts to make Auvelity available to patients living with MDD and their physicians.

重度抑鬱症（MDD）在美國目前面臨的重大公共衛生問題和心理健康危機中非常普遍。 2020 年，有 2100 萬成年人被確診，據報導，由於這一流行病，患病率顯著增加。對於患有這種慢性和破壞性疾病的患者來說，Auvelity 是一種重要的新治療選擇，我們為使 MDD 患者及其醫生能夠使用 Auvelity 所做的努力感到自豪。

Turning to Sunosi. In the first quarter, total prescriptions for Sunosi in the U.S. grew 13% year-over-year and 4% quarter-over-quarter. Sunosi generated this growth despite a flat overall market and typical Q1 challenges. Payer coverage for Sunosi remains broad with 96% of commercial lives and 83% of total lives covered.

轉向蘇諾西。第一季度，Sunosi 在美國的總處方量同比增長 13%，環比增長 4%。儘管整體市場表現平淡且存在典型的第一季度挑戰，Sunosi 仍實現了這一增長。 Sunosi 的付款人覆蓋範圍仍然廣泛，涵蓋 96% 的商業生活和 83% 的總生活。

The growth potential for Sunosi in the current approved indications remain substantial. As a reminder, Sunosi is the first and only DNRI for excessive time sleepiness and obstructive sleep apnea and narcolepsy and the person only wake-promoting agent proven to improve wakefulness through 9 hours.

Sunosi 在目前批准的適應症中的增長潛力仍然很大。提醒一下，Sunosi 是第一個也是唯一一個治療長時間嗜睡、阻塞性睡眠呼吸暫停和發作性睡病的 DNRI，也是唯一被證明可以在 9 小時內改善清醒狀態的促醒劑。

Sunosi is the only branded therapy available for patients who suffer from EDS and OSA, and we expect our increased and enhanced promotional and disease education efforts to drive continued growth for the product in 2023.

Sunosi 是唯一可用於 EDS 和 OSA 患者的品牌療法，我們預計我們增加和加強的宣傳和疾病教育工作將推動該產品在 2023 年持續增長。

We recently launched our new all day campaign for Sunosi. The new campaign includes updated creative content, additional HCP and patient support tools and new educational resources. Launching this new campaign is an important next step in the relaunch of Sunosi, and I look forward to updating you on our commercial efforts and results related to the Sunosi relaunch in the coming quarters. Our 2 commercial products, Auvelity and Sunosi address serious, highly prevalent conditions and bring meaningful innovation to millions of potential patients.

我們最近為 Sunosi 推出了新的全天活動。新活動包括更新的創意內容、額外的 HCP 和患者支持工具以及新的教育資源。啟動這項新活動是 Sunosi 重新啟動的重要下一步，我期待著在未來幾個季度向您介紹與 Sunosi 重新啟動相關的商業努力和成果。我們的 2 種商業產品 Auvelity 和 Sunosi 可解決嚴重、高度流行的病症，並為數百萬潛在患者帶來有意義的創新。

I will now turn the call back to Mark to lead the Q&A discussion.

現在，我將把電話轉回給馬克，讓他主持問答討論。

Thank you, Lori. Operator, may we please have our first question?

謝謝你，洛瑞。接線員，我們可以問第一個問題嗎？

(Operator Instructions) Our first question is coming from Charles Duncan from Cantor Fitzgerald.

（操作員說明）我們的第一個問題來自 Cantor Fitzgerald 的 Charles Duncan。

Congratulations on -- yes, a great quarter for Auvelity. Nice to see out of the gates. I had a couple of questions. One, commercial, one development or pipeline. Regarding the commercial question, on Auvelity, I'm wondering if Lori can provide any more granular feedback on what she has heard from prescribers hearing from patients in terms of those patients who have been on other drugs in the past and how this differentiated mechanism is helping them feel and the potential for persistence?

恭喜——是的，Auvelity 度過了一個偉大的季度。很高興看到門外。我有幾個問題。一項，商業，一項開發或管道。關於商業問題，在 Auvelity 上，我想知道 Lori 是否可以就她從處方者那裡聽到的患者的意見提供更詳細的反饋，這些反饋涉及過去服用過其他藥物的患者以及這種差異化機制是如何實現的。幫助他們感受並堅持下去的潛力？

Charles, thanks for the question. So I think the best way to answer that is to, one, take a look at script trends and how many patients we actually added in Q1. We added over 15,000 patients in Q1, and so physicians are clearly seeing a benefit of the product, but we're also seeing a really healthy refill rate right now. And I think that's really going to speak to the persistence and compliance. It's still a little bit too early into Q1 with only 5 months into launch. Still a little bit too early to see true trends on persistence and compliance, but the refill rate is really, really healthy.

查爾斯，謝謝你的提問。因此，我認為回答這個問題的最佳方法是，第一，看看腳本趨勢以及我們在第一季度實際添加的患者數量。我們在第一季度增加了 15,000 多名患者，因此醫生清楚地看到了該產品的好處，但我們現在也看到了非常健康的補充率。我認為這確實說明了堅持和服從。現在進入第一季度還為時過早，距發布僅 5 個月。現在要看到持久性和依從性的真正趨勢還為時過早，但補充率確實非常健康。

And I guess I can assume -- can we assume that now almost halfway through the second quarter, you feel pretty good about tone of business?

我想我可以假設——我們可以假設現在第二季度已經過半了，你對業務基調感覺很好嗎？

Absolutely. As I mentioned in the prepared remarks, we are really heavily investing in the optimization of the product. In terms of all the omnichannel approach we're taking from a marketing standpoint, strategic media, congresses, speaker programs, our sales force with high-impact engagements, and I qualify high-impact engagements with either detailing the physician and/or speaker programs, they've reached over 22,000 HCPs, and that's a lot of HCPs with (inaudible). We're really happy.

絕對地。正如我在準備好的發言中提到的，我們確實在產品優化方面投入了大量資金。就我們從營銷角度採取的所有全渠道方法而言，戰略媒體、大會、演講者計劃、我們的銷售人員具有高影響力的參與，我通過詳細介紹醫生和/或演講者計劃來限定高影響力的參與，他們已經覆蓋了超過 22,000 名 HCP，其中很多 HCP 都擁有（聽不清）。我們真的很高興。

And moving to the pipeline, I struggled to ask just one question, but I will ask just one question for Herriot because you've got a lot of things going on. I guess on 05, let's talk about that. You mentioned ADVANCE-2 enrollment is proceeding well, I'm wondering if you, on a blinded basis, feel good about the phenotype of the patient that you're enrolling? And if you can provide us any color? And then if you've learned anything from the recent result AdCom in terms of Alzheimer's agitation, how does that impact change or not your strategy with regard to 05 in Alzheimer's agitation?

談到管道，我很難只問一個問題，但我只會向赫里奧特問一個問題，因為有很多事情正在發生。我想在05年，我們來討論一下這個問題。您提到 ADVANCE-2 招募進展順利，我想知道您是否在盲法基礎上對您正在招募的患者的表型感覺良好？如果你能為我們提供任何顏色？那麼，如果您從 AdCom 最近關於阿爾茨海默氏症躁動的結果中了解到任何信息，那麼這對您關於阿爾茨海默氏症躁動的 05 策略的改變有何影響？

Thanks, Charles, for the questions. With regards to the types of patients that we are enrolling in advance to, I think we're -- we feel comfortable that we are enrolling a very similar type of patient as we enrolled in ADVANCE-1. The protocols are very similar. The entry criteria are very similar. I think the team is executing on enrolling the study and making sure that we have the right patients and that we have a quality trial again.

謝謝查爾斯提出的問題。關於我們提前招募的患者類型，我認為我們對招募與 ADVANCE-1 中招募的患者類型非常相似感到滿意。這些協議非常相似。進入標準非常相似。我認為團隊正在執行這項研究的註冊工作，並確保我們擁有合適的患者，並且我們再次進行高質量的試驗。

With regards to any learnings from the recent panel, there are a few observations. One is it became clear or it's been clear to us, but now I think it's been made publicly clear that the FDA as well as experts really feel that this is a high unmet medical need. So what panel highlighted was the seriousness of the condition and the quandary, frankly, that physicians find themselves in with no drugs that are approved and the only drugs that are used off label broadly are antipsychotics, which are problematic. So it's gratifying to be able to share that and do more broadly that awareness.

關於從最近的小組中獲得的任何經驗教訓，有一些觀察結果。一是它已經變得很清楚，或者我們已經很清楚了，但現在我認為已經公開表明 FDA 和專家確實認為這是一個高度未滿足的醫療需求。因此，小組強調的是病情的嚴重性和困境，坦率地說，醫生髮現自己沒有獲得批准的藥物，唯一廣泛使用的藥物是抗精神病藥物，這是有問題的。因此，能夠分享這一點並更廣泛地提高這種意識是令人高興的。

The other learning from the panel is that the way that we are going about developing the product is consistent with how the FDA views that it should be developed in terms of end points. And again, this is not anything which is new to us because we always work very closely with the FDA for this breakthrough therapy designated product candidate, but it's nice to see those points discussed in a public forum.

從專家組得到的另一個教訓是，我們開發該產品的方式與 FDA 認為應該根據終點進行開發的方式是一致的。再說一遍，這對我們來說並不是什麼新鮮事，因為我們始終與 FDA 密切合作，開發這種突破性療法指定的候選產品，但很高興看到在公共論壇上討論這些觀點。

Our next question is coming from Jason Gerberry from Bank of America.

我們的下一個問題來自美國銀行的 Jason Gerberry。

This is Dena on for Jason. Congrats on the progress this quarter. Just a couple on Auvelity here, how much did Auvelity 1Q benefit from inventory stocking? And do you have a firmer handle on the full year growth to net pricing dynamics? Or is that still more of a second half of the year event when you get to a more normalized rate?

這是德娜為傑森做的。祝賀本季度取得的進展。就 Auvelity 而言，Auvelity 第一季度從庫存備貨中受益了多少？您對全年淨定價動態增長是否有更堅定的把握？或者當你達到更正常化的利率時，這仍然是今年下半年的事件嗎？

Dena, it's Nick. Thanks for the question. The performance for Auvelity was not impacted by changes in the inventory level. As we've stated previously, normal inventory levels are at around 2 weeks. And during the quarter, there was actually a modest decrease in days on hand of Auvelity to the distributors. So overall, it was not impactful at all to the net sales.

德娜，是尼克。謝謝你的提問。 Auvelity 的業績並未受到庫存水平變化的影響。正如我們之前所說，正常庫存水平約為兩週。在本季度，分銷商的 Auvelity 庫存天數實際上略有減少。總體而言，這對淨銷售額沒有任何影響。

In contrast for Sunosi, as we mentioned, there was an impact of $3.3 million due to the change of title, reported sales would have been $3.3 million, additional has there been no change on that.

相比之下，正如我們所提到的，Sunosi 因名稱變更而受到了 330 萬美元的影響，如果沒有任何變化，報告的銷售額將為 330 萬美元。

And I think your second question related to how do we think about GTN for the remainder of the year. We're still not currently in a position to give specific guidance around GTN as it's going to be volatile in the short term. Obviously, there's coverage mix that's going to be -- sorry, there's mix in channel throughout the year that we're going to have distribution.

我認為你的第二個問題與我們如何看待今年剩餘時間裡的 GTN 有關。我們目前仍無法就 GTN 提供具體指導，因為它在短期內會出現波動。顯然，會有多種報導組合——抱歉，我們將在全年進行分發。

Coverage is going to be dynamic and coming online as we've seen it. It's going to continue to come online throughout the year. And then also the utilization of the co-pay card. So while we are pleased with the GTN this quarter, we don't expect it to improve in the near term.

正如我們所看到的，報導將是動態的並在線進行。它將全年繼續上線。然後還有共同支付卡的使用。因此，雖然我們對本季度的 GTN 感到滿意，但我們預計它在短期內不會有所改善。

Your next question is coming from Marc Goodman from SVB Securities.

您的下一個問題來自 SVB 證券公司的馬克·古德曼 (Marc Goodman)。

Yes. Could you give us a sense of commercial coverage, how you're planning that? I know that it's been kind of a slow process at the beginning on purpose. I was wondering, is this going to speed up as the year progresses? And how much of an impact did volumes get helped by the one contract that you've talked about already?

是的。您能給我們介紹一下商業報導的情況嗎？您是如何計劃的？我知道一開始這是一個故意緩慢的過程。我想知道，隨著時間的推移，這種情況會加速嗎？您已經談到的一份合同對銷量產生了多大的影響？

And then second question is just the SG&A run rate in the quarter. Just give us a sense of -- is that the run rate going forward? Should we expect that to kind of ramp from there? Or does that include some upfront costs for the year?

第二個問題是本季度的 SG&A 運行率。讓我們了解一下——這是未來的運行率嗎？我們是否應該期望這種情況會從那裡開始？或者這是否包括今年的一些前期費用？

Marc, I'll address the first question and pass it over to Nick. So as we said before, we have expected access to start coming online around 6 to 9 months post-launch and given we are fairly at 6 months when we're at 65% of life cover. We're feeling pretty good about where we're at with life covered, and we do expect that to continue to evolve over the course of the next few months to the rest of the year.

馬克，我將解決第一個問題並將其傳遞給尼克。因此，正如我們之前所說，我們預計在發布後 6 到 9 個月左右即可開始上線，並且考慮到我們在 6 個月內就達到了 65% 的生命覆蓋率。我們對目前的生活狀況感覺非常好，我們確實希望這種情況在未來幾個月到今年剩餘時間裡繼續發展。

I want to talk about just volumes in terms of the contracts that we have in place. We don't necessarily look at it that way. I'll give you some numbers to think through. And that is 90% of patients who have been prescribed Auvelity are first line -- have failed first line therapy. 60% of patients are second and third line. And this is exactly where we would expect patients to be right now.

我只想談談我們現有合同的數量。我們不一定這麼看。我會給你一些數字供你思考。也就是說，90% 接受 Auvelity 處方的患者都是一線治療，一線治療失敗了。 60%的患者處於二線和三線。這正是我們期望患者現在所處的位置。

One, because there is an urgent and unmet need out in the marketplace; but two, as they work through formulary access. And so we are seeing a healthy amount of patients using the product later line, obviously, with nice success and the continued improvement in terms of moving the line of therapy up.

一是因為市場上存在緊急且未滿足的需求；但有兩個，因為它們是通過處方獲得的。因此，我們看到大量患者在使用該產品的後續產品線，顯然取得了巨大的成功，並且在提升治療線方面取得了持續改進。

Part of that is helped by the fact that we have a robust patient support services program in place and the patient support services program is really in place to make sure that patients that want therapy are able to go there.

部分原因是我們擁有強大的患者支持服務計劃，並且患者支持服務計劃確實到位，以確保需要治療的患者能夠去那裡。

Marc, I'll take the second part of your question on the SG&A. And actually, Q1, we did have some onetime charges as related to the Pharmanovia license. While we're not offering specific guidance for the rest of the year, I would point you to taking a look at what we spent in Q4 as well as Q1 as a ballpark of where we would expect to be in the future quarters for 2023.

馬克，我將回答您關於 SG&A 問題的第二部分。事實上，第一季度，我們確實有一些與 Pharmanovia 許可相關的一次性費用。雖然我們不會為今年剩餘時間提供具體指導，但我建議您看一下我們在第四季度和第一季度的支出，作為我們預計 2023 年未來幾個季度的大致情況。

Your next question is coming from David Amsellem from Piper Sandler.

您的下一個問題來自 Piper Sandler 的 David Amsellem。

So a couple for me. On Auvelity, can you just talk to qualitatively the kinds of patients who are getting the drug in terms of how many prior treatments you're seeing prior exposure to SSRIs, SNRIs, bupropion, et cetera? That's number one.

所以對我來說是一對。在 Auvelity 上，您能否根據您之前接受過 SSRI、SNRI、安非他酮等治療的次數來定性地討論正在接受該藥物治療的患者類型？這是第一。

And then secondly, on reboxetine, I'm trying to tease out how you're thinking about the product in the context of the current treatment landscape and particularly given that there's some mechanistic overlap with Sunosi. As you think about narcolepsy, where do you see reboxetine fitting in commercially, of course, assuming that there's clinical success?

其次，關於瑞波西汀，我試圖弄清楚您在當前治療環境的背景下如何看待該產品，特別是考慮到與 Sunosi 存在一些機制上的重疊。當您想到發作性睡病時，您認為瑞波西汀在商業上的適合性在哪裡，當然，假設臨床上取得了成功？

David, I'll take the first one and then pass it over to Herriot. So as I just mentioned to Marc, right now, we're seeing 90% of patients have failed one therapy, but that's not unusual or exactly as we had expected. 60% to 65% have been on second and third line therapies prior. And so we are seeing later line use, which is exactly as we would expect coming out of the gate. Again, this is consistent with the unmet need in that patient population.

大衛，我將接受第一個，然後將其傳遞給赫里奧特。正如我剛才向 Marc 提到的，現在我們看到 90% 的患者在一種治療中失敗，但這並不罕見，或者與我們預期的完全一樣。 60% 至 65% 之前曾接受過二線和三線治療。因此，我們看到了後來的線路使用，這正是我們所期望的。同樣，這與該患者群體中未滿足的需求是一致的。

We are seeing obviously success as objective evidence shows from refill rates as well as what we're hearing from the field. And as we -- AXS opens up and physicians get clinical experience, we do anticipate that ability will move up our near line usage.

從補充率以及我們從現場聽到的情況來看，我們看到了明顯的成功。隨著我們 AXS 的開放以及醫生獲得臨床經驗，我們確實預計這種能力將提高我們的近線使用率。

Great. And with regards to AXS-12 or reboxetine, you mentioned (inaudible) with Sunosi and how would we think about the 2 products? So reboxetine is being developed for narcolepsy primarily for cataplexy. So what we saw in the Phase II trial was that there was a robust effect on cataplexy and also an effect on excessive sleepiness. As a reminder, Sunosi has robust effects on excessive day sleepiness, but is not approved to treat cataplexy. So the 2 products that would be complementary.

偉大的。關於 AXS-12 或瑞波西汀，您提到（聽不清）Sunosi，我們會如何看待這兩種產品？因此，瑞波西汀正在開髮用於治療發作性睡病，主要用於治療猝倒症。所以我們在第二階段試驗中看到的是，它對猝倒有很強的作用，對過度嗜睡也有作用。提醒一下，Sunosi 對於白天過度嗜睡有很強的效果，但未被批准用於治療猝倒症。所以這兩種產品是互補的。

Now we like the profile that we saw in the Phase II trial for AXS-12. And we're looking forward to seeing what the results of the Phase III trial are, and that's going to inform us in terms of the full profile of the product.

現在我們喜歡在 AXS-12 II 期試驗中看到的概況。我們期待看到第三階段試驗的結果，這將讓我們了解該產品的完整概況。

That's helpful. If I may sneak in a follow-up, do you think reboxetine on cataplexy has to be markedly better than what we typically see for off-label uses of dual uptake inhibitors like venlafaxine and duloxetine, because I know there is some off-label use. How do you think about that?

這很有幫助。如果我可以偷偷地進行後續跟踪，您是否認為瑞波西汀治療猝倒症必須明顯優於我們通常看到的雙重攝取抑製劑（如文拉法辛和度洛西汀）的標籤外使用，因為我知道有一些標籤外使用。您對此有何看法？

It's -- that's a hard question to answer because there have been no controlled trials with any of those agents. So a lot of it is anecdotal. And what we can speak to is the profile of our product. And we think that, that the profile is very attractive. So a drug, which is -- which has an effect on both cataplexy as well as excessive daytime sleepiness, which is dosed during the day, which does not have a lot of the scheduling or a lot of, frankly, the serious side effect concerns of the agents that are currently marketed.

這是一個很難回答的問題，因為還沒有對這些藥物進行過對照試驗。所以很多都是軼事。我們可以談論的是我們產品的概況。我們認為，這個形象非常有吸引力。因此，這種藥物對猝倒和白天過度嗜睡都有影響，白天服用，沒有太多的時間安排，或者坦率地說，有很多嚴重的副作用問題目前上市的代理。

Next question is coming from Joon Lee from Truist Securities.

下一個問題來自 Truist Securities 的 Joon Lee。

Sorry if I misheard, but I think I heard Lori just say that 90% of the patients have failed at least one therapy before getting on Auvelity. Does that mean that there are 10% who get Auvelity as first-line therapy? I just want to make sure I heard that correctly. And I have a follow-up.

抱歉，如果我聽錯了，但我想我聽到 Lori 剛剛說過，90% 的患者在接受 Auvelity 治療之前至少已經失敗過一種治療。這是否意味著有 10% 的人接受 Auvelity 作為一線治療？我只是想確保我聽到的是正確的。我有一個後續行動。

Joon, thanks for the question. There's always going to be some early line uses, it could be either data reporting or it could just be patients who are paying out of pocket potentially, it could also be medical necessity writing through -- getting through to that line. This is just reported data that we're seeing, and we're seeing 90% are -- have failed one prior therapy, which is exactly what we would expect at this point.

瓊，謝謝你的提問。總會有一些早期的線路用途，可能是數據報告，也可能只是患者自付費用，也可能是醫療必需品——接通該線路。這只是我們看到的報告數據，我們看到 90% 的患者之前的一種治療都失敗了，這正是我們目前所期望的。

Has that share of first-line use gone up over time?

隨著時間的推移，一線用藥的比例是否有所上升？

No, it's actually gone down.

不，實際上已經下降了。

Okay. Got it. And at high level, Auvelity gross net for first quarter looks like around 50%. Is that in the ballpark? And if so, could we expect further improvement in that gross net? Or are we -- do you think you're already at the more or less the steady state?

好的。知道了。從高水平來看，Auvelity 第一季度的總淨值約為 50%。是在球場裡嗎？如果是這樣，我們可以期待總淨值進一步改善嗎？或者我們——你認為你已經或多或少處於穩定狀態了嗎？

Yes, Joon, I think what I actually said is the GTN is in the high upper 50s is where it was for Q1, and we wouldn't expect that to materially change or improve in the next future quarters.

是的，Joon，我想我實際上說的是 GTN 處於 50 多歲的高位，這是第一季度的情況，我們預計這一情況不會在未來幾個季度發生重大變化或改善。

Next question today is coming from Vikram Purohit from Morgan Stanley.

今天的下一個問題來自摩根士丹利的 Vikram Purohit。

So first, just a quick clarification question for ADA. Could you just remind us exactly which data sets you plan to include in the eventual filing for ADA, assuming your data set with ADVANCE-2 matures positively?

首先，我想向 ADA 快速澄清一個問題。假設您的 ADVANCE-2 數據集正在積極成熟，您能否準確提醒我們您計劃在最終的 ADA 申請中包含哪些數據集？

And then secondly, for AXS-12 in narcolepsy for the SYMPHONY data readout you expect in the coming months. Could you remind us what the study is powered to demonstrate and what you would consider a kind of strong clinically meaningful outcome here?

其次，對於用於發作性睡病的 AXS-12，您期望在未來幾個月內讀出 SYMPHONY 數據。您能否提醒我們這項研究旨在證明什麼以及您認為什麼是具有強烈臨床意義的結果？

Thanks for the questions. With regards to Alzheimer’s disease agitation, in the filings -- in the S&D filing, we would include the results from all of the studies that we conducted. As a reminder, we've completed the ADVANCE-1 trial, which is a pivotal trial, the ADVANCE-2 trial, those data will also be included. So that mirrors the ADVANCE-1 trial. Also, data from the ACCORD trial will be included as well as data from the open-label safety extension trial. So the long-term open-label safety extension trial. So it will be a pretty full package, and we look forward to reading out the ADVANCE-2 trial and if that's positive in filing the sNDA.

感謝您的提問。關於阿爾茨海默病的躁動，在 S&D 文件中，我們將包括我們進行的所有研究的結果。提醒一下，我們已經完成了 ADVANCE-1 試驗，這是一項關鍵試驗，ADVANCE-2 試驗也將包括在內。這反映了 ADVANCE-1 試驗。此外，ACCORD 試驗的數據以及開放標籤安全性擴展試驗的數據也將包括在內。因此進行長期的開放標籤安全性延伸試驗。因此，這將是一個相當完整的方案，我們期待宣讀 ADVANCE-2 試驗，以及提交 sNDA 時是否有積極作用。

And with regards to AXS-12 in terms of the powering of the study. So the study is 90% powered to detect a change on the cataplexy endpoint. So that's the primary endpoint. So we've not disclosed what that delta is that we are expecting, but what we can point you to or the results from the CONCERT trial, the Phase II trial and it was based upon those results that we powered our study.

至於 AXS-12 的研究動力。因此，該研究有 90% 的能力檢測到猝倒終點的變化。這就是主要終點。因此，我們還沒有透露我們所期望的增量是什麼，但我們可以向您指出什麼，或者 CONCERT 試驗、第二階段試驗的結果，它是基於我們為我們的研究提供支持的這些結果。

Our next question is coming from Yatin Suneja from Guggenheim Partners.

我們的下一個問題來自古根海姆合夥人公司的 Yatin Suneja。

A couple of questions for me. I don't know if you articulated what the exact gross to net was or what the approximate gross to net was for Q1. So that's one. Any thoughts on providing guidance for sales for Auvelity when you might do that? And then if you can articulate for us the cadence of patients, whether it's a weekly cadence or a monthly cadence, where it is, how do you expect that to change over time?

有幾個問題問我。我不知道您是否闡明了第一季度的確切淨毛額或淨毛額的近似值。這就是其中之一。當您可能這樣做時，您對為 Auvelity 提供銷售指導有什麼想法嗎？然後，如果您能為我們闡明患者的節奏，無論是每週節奏還是每月節奏，它在哪裡，您預計隨著時間的推移會如何變化？

Yatin, again, gross to net for Auvelity in the quarter was in the high upper 50s. This was an improvement from the 60s in Q4, that was due to a higher proportion of refills of scripts versus new scripts. Again, we're very pleased, obviously, with the GTN this quarter, but we don't anticipate it to improve in the near term.

Yatin 再次表示，本季度 Auvelity 的總淨收入處於 50 多歲的高位。與 20 世紀 60 年代第 4 季度相比，這是一個進步，這是因為與新腳本相比，重新填充腳本的比例更高。顯然，我們對本季度的 GTN 感到非常滿意，但我們預計它在短期內不會有所改善。

And then as it relates to sales guidance, we're in a very early stages of the launch of Auvelity along with acquiring Sunosi, just up to a year now. And as such, we find it just really premature to provide any such guidance as there's multiple variables that can affect this number. I think, Lori, you want to answer the last question?

然後，就銷售指導而言，我們正處於推出 Auvelity 以及收購 Sunosi 的早期階段，距今僅一年時間。因此，我們發現提供任何此類指導確實為時過早，因為有多個變量可能影響這個數字。我想，洛瑞，你想回答最後一個問題嗎？

Yes, yes. 100% sure. What you meant by the question, but the scripts are written on a monthly basis. And so patients are -- we are tracking monthly prescriptions.

是的是的。 100%確定。你問這個問題的意思是什麼，但是腳本是按月編寫的。因此，我們正在跟踪患者每月的處方。

Next question is coming from Joseph Thome from TD Cowen.

下一個問題來自 TD Cowen 的 Joseph Thome。

Congrats on the quarter. Maybe the first one on AXS-12. I know you said the focus was largely going to be on the cataplexy endpoint, but do you anticipate releasing sleepiness scores as well when you report the full data? And then just as you think about the filing package, if these data are positive here, can you comment on the safety database and sort of CMC metrics? Are you ready to file a submission if the data are positive? Or kind of where do you follow on that?

恭喜本季度。也許是 AXS-12 上的第一個。我知道您說過重點主要放在猝倒終點上，但您是否預計在報告完整數據時也會發布嗜睡評分？然後，正如您考慮歸檔包一樣，如果這些數據在這裡是積極的，您能否對安全數據庫和 CMC 指標進行評論？如果數據是積極的，您準備好提交提交嗎？或者你對此有何看法？

Sure. Thanks for the question. So when we report top line results historically, we've reported a number of different endpoints. So we don't expect the SYMPHONY readout to be any different. So we'll try and provide as much information as we can given the constraints of reporting top line results from large data sets.

當然。謝謝你的提問。因此，當我們報告歷史上的頂線結果時，我們報告了許多不同的端點。因此，我們預計 SYMPHONY 讀數不會有任何不同。因此，考慮到從大型數據集報告頂線結果的限制，我們將嘗試提供盡可能多的信息。

And with regards to the filing package. In terms of the safety database, we still need to finalize with the FDA, what would be included in the safety database. But preliminarily, we have a lot of safety data. So we're conducting -- we are collecting safety data not only from the studies that we have conducted, but also as a reminder, we did in-license a very large patient safety database for reboxetine through our Pfizer agreement.

關於歸檔包。在安全數據庫方面，我們仍然需要與FDA最終確定安全數據庫中應包含哪些內容。但初步來說，我們有很多安全數據。因此，我們不僅從我們已經進行的研究中收集安全數據，而且作為提醒，我們確實通過輝瑞協議許可了一個非常大的瑞波西汀患者安全數據庫。

And on the CMC front, things are progressing well there. So we do manufacture, we do synthesize that the API ourselves. So right now, that's been going smoothly and everything is going smoothly on the CMC side.

在中央軍事委員會方面，事情進展順利。所以我們自己製造、合成 API。現在，一切進展順利，中央軍委方面一切進展順利。

And then with regards to when we would actually be able to file an NDA, a gating factor will be the completion of the long-term safety study. So assuming that we do have success with the SYMPHONY trial, we would expect being able to file an NDA likely in 2024.

然後，關於我們何時真正能夠提交 NDA，一個限制因素將是長期安全研究的完成。因此，假設我們的 SYMPHONY 試驗確實取得了成功，我們預計能夠在 2024 年提交 NDA。

Great. That's very helpful. And then maybe, Lori, definitely helpful on the prescriber base and sort of unique writers. Can you go into a little bit more detail in terms of how physicians are prescribing this. Are they trying it first in one patient and then if that goes well, they go in other patients? Once you get a writer, do they write a lot of prescriptions? Kind of how is it getting these physicians onboard? And how will that change kind of for the duration of the year do you think?

偉大的。這非常有幫助。也許，洛瑞，對處方者基礎和獨特的作家絕對有幫助。您能更詳細地介紹一下醫生是如何開這個藥的嗎？他們是否會先在一名患者身上進行嘗試，然後如果進展順利，再在其他患者身上進行嘗試？一旦你找到了一位作家，他們會寫很多處方嗎？如何讓這些醫生加入進來？您認為這一年中這種情況會發生怎樣的變化？

Yes. Yes, it's a great question. So consistent with expectations of launch, you have your early adopters that come out of the gate prescribing. And those -- if they have clinical success, that's how they have tremendous depth, and we are seeing exactly that. The writers that have written they have really incredible market share in terms of their use of Auvelity, so they're seeing positive clinical experience.

是的。是的，這是一個很好的問題。與發布的預期一致，您的早期採用者會從一開始就開處方。而那些——如果他們在臨床上取得了成功，那就是他們擁有巨大的深度，而我們正是看到了這一點。撰寫文章的作者們在使用 Auvelity 方面擁有令人難以置信的市場份額，因此他們看到了積極的臨床經驗。

And then as you move further along with the launch and you're trying to increase your breadth, then you start seeing writers that are on an adoption curve that may need a little bit more time and market understanding peer influence or they may need clinical experience from one patient before they write more. So we're starting to get into that and our breadth is starting to grow. As I mentioned, in Q1, we added 3,800 new unique HCP writers. And so we definitely expect that to continue to grow just as a normal adoption curve would progress.

然後，當您進一步推進發布並嘗試增加廣度時，您開始看到處於採用曲線上的作家可能需要更多的時間和市場了解同行的影響，或者他們可能需要臨床經驗在他們寫更多之前，來自一位患者。所以我們開始涉足這一領域，我們的廣度也開始擴大。正如我提到的，在第一季度，我們新增了 3,800 名獨特的 HCP 作家。因此，我們肯定預計這一數字將繼續增長，就像正常的採用曲線一樣。

Next question today is coming from Graig Suvannavejh from Mizuho Securities.

今天的下一個問題來自瑞穗證券 (Mizuho Securities) 的 Graig Suvannavejh。

Congrats on the quarter. I had a couple of questions. Just wanted to get a sense of maybe philosophically speaking, where you are in terms of your commercial infrastructure and whether given the opportunity you're content to keep it sized the way it is right now? Or do you feel that perhaps you can be opportunistic and further drive even perhaps better uptake of Auvelity in particular?

恭喜本季度。我有幾個問題。只是想了解一下，也許從哲學上來說，您的商業基礎設施處於什麼位置，以及您是否願意有機會保持其目前的規模？或者您是否覺得也許您可以投機取巧，進一步推動甚至更好地吸收 Auvelity？

And then secondly, just wanted to get a sense of just going back to the gross to net and maybe just for clarification on my end. Just can you tell us how exactly you go about calculating your growth and I just want to make sure that I'm thinking about it the same way you're thinking about it?

其次，我只是想了解一下回到淨值的情況，也許只是為了澄清一下我的情況。你能告訴我們你到底是如何計算你的成長的嗎？我只是想確保我和你的想法是一樣的？

Graig, so GTN, I mean, it's basically, the way everybody else would essentially calculate gross to net. It's based on demand in the quarter and the utilization of co-pay card and any type of rebates, any additional adjustments as well. That all goes into GTN. We would also approve for anything that was sold in the quarter, that's sitting in the channel that has not been distributed to the pharmacies at that point. So that would also be considered part of the GTN adjustment for the period. Lori, do you want to answer the second one?

Graig，所以 GTN，我的意思是，這基本上是其他人計算毛淨值的方式。它基於本季度的需求以及共同支付卡的使用情況以及任何類型的回扣以及任何其他調整。這一切都進入 GTN。我們還將批准本季度銷售的任何產品，這些產品當時尚未分發到藥店。因此，這也將被視為該期間 GTN 調整的一部分。洛瑞，你想回答第二個問題嗎？

So not sure if you're meaning the Auvelity sales force or the Sunosi sales force, but I'll try and answer both because the answer is pretty applicable across both. So just to give you some perspective on the Auvelity side, there are about 50,000 HCPs who prescribe really the lion's share of branded therapies. We are calling on 25,000, 26,000 HCPs of those 50,000, but those 25,000 that we're calling on, they write almost 70% of the branded therapies.

所以不確定您指的是 Auvelity 銷售人員還是 Sunosi 銷售人員，但我會嘗試回答這兩個問題，因為答案非常適用於兩者。因此，為了讓您對 Auvelity 方面有一些看法，大約有 50,000 名 HCP 開出了大部分品牌療法的處方。我們正在拜訪這 50,000 名 HCP 中的 25,000 名、26,000 名 HCP，但是我們正在拜訪的這 25,000 名 HCP 中，幾乎 70% 的品牌療法都是他們撰寫的。

Our DCC platform was intentionally structured so that we could maintain a share of voice either through reach or with our omnichannel marketing of sales forces in some cases, 2x the size of what we have.

我們的 DCC 平台經過精心設計，以便我們可以通過影響力或在某些情況下通過銷售人員的全渠道營銷來保持一定的話語權，其規模是我們現有規模的兩倍。

Remember, our DCC platform was really set up so that we can optimize productivity through effective and efficient engagements. And right now, we are seeing that with our HCP targets. As we're able to reach as many targets as again, sales force that are somewhat upwards of 2x the size that we have right now.

請記住，我們的 DCC 平台的真正建立是為了讓我們能夠通過有效和高效的參與來優化生產力。現在，我們在 HCP 目標中看到了這一點。由於我們能夠再次實現盡可能多的目標，因此銷售隊伍的規模比我們現在的規模增加了 2 倍。

So as we are continuing to invest in both Auvelity and Sunosi through omnichannel marketing, strategic media, congress spending, speaker programs, as I've mentioned before, we will obviously continue to make sure that we're maximizing the opportunity for both products.

因此，正如我之前提到的，當我們繼續通過全渠道營銷、戰略媒體、國會支出、演講者計劃對 Auvelity 和 Sunosi 進行投資時，我們顯然將繼續確保最大限度地利用這兩種產品的機會。

Yes. And then what I would just add to what Lori said is that, right now, the -- our marketing efforts and the yield from that is going exactly as we had expected, exactly as we had planned. We said before that our field force sizing and targeting was based upon all of the data and information that we've looked at through our DCC platform. And so we feel that we are more than adequately resourced right now. We're very happy with the way that the launch is going. Obviously, anything can change, and we are in an organization that can be flexible. But for now, we're at a core resource.

是的。然後我要補充的是，洛里所說的是，現在，我們的營銷努力和由此產生的收益完全符合我們的預期，完全符合我們的計劃。我們之前說過，我們的現場部隊規模和目標是基於我們通過 DCC 平台查看的所有數據和信息。因此，我們認為我們現在的資源非常充足。我們對發布的方式非常滿意。顯然，任何事情都可能發生變化，而我們所在的組織可以保持靈活性。但就目前而言，我們擁有核心資源。

Our next question is coming from Myles Minter from William Blair.

我們的下一個問題來自威廉·布萊爾的邁爾斯·明特。

Congrats on the quarter. Can you just comment on the proportion of those 31,000 scripts for valid that are being reimbursed or seeking reimbursement through the commercial versus government channels? And does that differ materially from the broader branded antidepressant market, which I think is 2/3 commercial, 1/3 government?

恭喜本季度。您能否簡單評論一下這 31,000 個有效劇本中通過商業渠道和政府渠道進行報銷或尋求報銷的比例？這與更廣泛的品牌抗抑鬱藥市場（我認為 2/3 是商業的，1/3 是政府的）有本質上的不同嗎？

Yes. Myles, we are seeing exactly -- almost exactly what we see in the broader antidepressant category. So the broader antidepressant category is about 60% to 65% commercial and the remaining the government channel, and that is spot on. We may be feeling a little bit heavier to commercial. I think we're around 70% right now, but it's exactly as expected.

是的。邁爾斯，我們所看到的正是——幾乎正是我們在更廣泛的抗抑鬱藥物類別中所看到的。因此，更廣泛的抗抑鬱藥物類別大約有 60% 到 65% 是商業渠道，其餘的是政府渠道，這是正確的。我們可能對商業化感覺有點沉重。我認為我們現在大約是 70%，但這完全符合預期。

Okay. Cool. And then the second one is just on the SYMPHONY trial. You mentioned powering assumptions or so like or in concert, does that mean that the baseline cataplexy rates over the week are going to be similar between those 2 trials when they read out?

好的。涼爽的。然後第二個就在 SYMPHONY 試驗中。您提到了類似或一致的動力假設，這是否意味著當他們讀出時，這兩個試驗之間的一周基線猝倒率將相似？

So the entry criteria are similar. And whether or not the actual numbers are the same that remains to be seen, but the entry criteria are similar. There's a lot of variability with regards to cataplexy in patients. And part of the reason for that is that cataplexy, although it is a symptom that everybody has, it is triggered. So there'll be variability from -- amongst individual patients based on their social situations.

所以進入標準是相似的。實際數字是否相同還有待觀察，但進入標準是相似的。患者猝倒的情況存在很大差異。部分原因是猝倒症，雖然這是每個人都有的症狀，但它是被觸發的。因此，根據患者的社會狀況，個體患者之間會有差異。

We have time for 2 more questions. Our next question is coming from Matt Kaplan from Ladenburg Thalmann.

我們還有時間回答 2 個問題。我們的下一個問題來自拉登堡塔爾曼的馬特·卡普蘭。

Congrats on the results of the quarter. Just wanted to zero in a little bit on Sunosi supplemental in the ADHD indication and your plans for the Phase III program. Can you talk about -- a little bit about the indication and the need there and then your Phase III program -- initial study, would that be potentially sufficient for filing as possible.

祝賀本季度的業績。只是想將 ADHD 適應症中的 Sunosi 補充品和您的第三階段計劃的計劃歸零。您能否談談 - 一點關於那裡的適應症和需求，然後是您的第三階段計劃 - 初步研究，這是否足以提交盡可能的文件。

Thanks, Matt, for the question. So ADHD is a very large market. There are roughly 12 million patients in the U.S. who have ADHD. And right now, they were treated either with stimulants, which are -- which have issues with regards to diversion and because they're highly controlled. These are drugs that are very effective, that have a very large effect size, but then there are the downside from a safety perspective. And then they are the non-stimulant medications what they suffer from or lower effect sizes. So there is a very large need still for effective drugs that are both effective and also that have a very good safety profile.

謝謝馬特提出的問題。所以多動症是一個非常大的市場。美國大約有 1200 萬多動症患者。現在，他們要么接受興奮劑治療，要么在轉移方面存在問題，因為它們受到高度控制。這些藥物非常有效，作用範圍非常大，但從安全角度來看也存在缺點。然後它們是非刺激性藥物，它們所遭受的影響或較小的效應大小。因此，仍然非常需要既有效又具有良好安全性的有效藥物。

We like Sunosi based on the comparison, let's say, in other indications. So in excessive daytime sleepiness, for example, where the clinical trial results show that it appears to be superior agent to other drugs -- to other wake-promoting agents, for example. And we also very much like the results from the SHARP study, which recently read out where we looked specifically at cognition in patients with OSA. So it's not directly analogous, but we like the clinical profile of the drug in other indications. We like the mechanism of action of the drug. Also, we recently announced that it hits TOR1, which in preclinical models have been shown to be procognitive. So there's a lot there that we hope to test in the upcoming trial, which we expect to start this quarter.

我們喜歡 Sunosi 是基於比較，比如說，在其他方面。例如，在白天過度嗜睡的情況下，臨床試驗結果表明，它似乎比其他藥物（例如其他促醒藥物）更有效。我們也非常喜歡 SHARP 研究的結果，該研究最近公佈了我們專門研究 OSA 患者認知的情況。所以它不是直接類似的，但我們喜歡該藥物在其他適應症中的臨床特徵。我們喜歡該藥物的作用機制。此外，我們最近宣布它擊中了 TOR1，在臨床前模型中已證明 TOR1 具有前瞻性。因此，我們希望在即將於本季度開始的試驗中測試很多內容。

And then with regards to what would be needed in order to file, so to file an NDA or an sNDA for drug in ADHD, you also do need to demonstrate efficacy in a pediatric population. So the study that we're about to launch, that is a study in adults and we will be also looking to initiate a study in pediatric patients to enable a filing.

然後，關於提交 ADHD 藥物的 NDA 或 sNDA 所需的材料，您還需要證明在兒科人群中的療效。因此，我們即將啟動的研究是一項針對成人的研究，我們還將尋求針對兒童患者啟動一項研究以進行備案。

Okay. That's very helpful. And then a quick question for Lori. In terms of some near-term NDA filings, can you talk about the launch prep you have underway for AXS-07 and potentially 14 as well given the timing of those NDAs and filings?

好的。這非常有幫助。然後問洛瑞一個簡單的問題。就一些近期的 NDA 申請而言，您能否談談您為 AXS-07 以及可能的 14 號產品進行的發射準備工作？考慮到這些 NDA 和申請的時間安排？

Yes. Thanks for the question. So 07, if you remember, we got all of this up to the finish line. So launch prep was pretty heavily done there. So in terms of marketing materials and the preparation for the market and understanding, that's all just -- we need to do a refresh. Based on timing for both 07 and 14 will be when we decide structure thoughts on sales force sizing. So once we have a little bit more understanding on the exact timing and dates, then we'll share what that looks like.

是的。謝謝你的提問。所以 07，如果你還記得的話，我們把這一切都完成了。因此，發射準備工作在那裡進行得非常充分。因此，就營銷材料以及市場準備和理解而言，我們需要進行更新。根據 07 年和 14 年的時間安排，我們將決定銷售人員規模的結構想法。因此，一旦我們對確切的時間和日期有了更多的了解，我們就會分享具體情況。

Our final question is coming from Raghuram Selvaraju from H.C. Wainwright.

我們的最後一個問題來自 H.C. 的 Raghuram Selvaraju。溫賴特。

This is Boobalan dialing in for Ram Selvaraju. A couple from us. So firstly, I'd like to get your thoughts on intracellular therapeutics, lumateperone, which produced positive top line data as monotherapy in patients with MDD and bipolar depression. Whether any takeaways with respect to future clinical directions for AXS-05 on this recently reported data?

我是 Boobalan，正在撥通 Ram Selvaraju 的電話。我們的一對。首先，我想了解一下您對細胞內療法 Lumateperone 的看法，該療法作為 MDD 和雙相抑鬱症患者的單一療法產生了積極的頂線數據。根據最近報告的數據，是否對 AXS-05 未來的臨床方向有任何啟發？

Thanks for the questions. With regards to lumateperone and the data in mood disorders, it's not surprising that an antipsychotic would work in depression. So I think it's well known that atypical antipsychotics are used as adjunctive treatment.

感謝您的提問。就魯美特哌隆和情緒障礙的數據而言，抗精神病藥物對抑鬱症有效並不奇怪。所以我認為非典型抗精神病藥物被用作輔助治療是眾所周知的。

So -- and any time, any company generates data in depression or in bipolar depression, which is positive. We think that that's a great thing because there is -- the need is so large and the patient population is so large. And there's such a large amount of heterogeneity in terms of response from patients. So yes, that's great, and let's have more of that.

因此，任何時候，任何公司都會生成有關抑鬱症或躁鬱症的數據，這是積極的。我們認為這是一件偉大的事情，因為需求如此之大，患者群體如此之大。患者的反應存在很大的異質性。所以，是的，這太棒了，讓我們有更多這樣的經歷。

We reached the end of our question-and-answer session. I'd like to turn the floor back over to management for any further or closing comments.

我們的問答環節結束了。我想將發言權交還給管理層，以徵求進一步的意見或結束意見。

Well, thank you again for joining us on the call today, and we saw strong performance in all areas of our business in the first quarter. We are executing on the commercialization of Auvelity and Sunosi, and we are advancing our late-stage pipeline to key milestones in multiple indications.

好吧，再次感謝您今天參加我們的電話會議，我們在第一季度的所有業務領域都看到了強勁的業績。我們正在執行 Auvelity 和 Sunosi 的商業化，並且正在將我們的後期研發管線推進到多個適應症的關鍵里程碑。

Our marketed and development portfolio positions us to have potentially at least 5 marketed products by 2025, targeting brain disorders that affect tens of millions of people. And also, these are conditions where there's still a great unmet medical need. So we look forward to updating you on our progress during the rest of the year. Have a great rest of your day. Thank you.

我們的營銷和開發產品組合使我們能夠在 2025 年之前擁有至少 5 種上市產品，針對影響數千萬人的腦部疾病。而且，在這些情況下，仍然存在大量未滿足的醫療需求。因此，我們期待向您通報我們在今年剩餘時間裡取得的最新進展。祝您度過愉快的一天。謝謝。

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.

謝謝。今天的電話會議和網絡廣播到此結束。此時您可以斷開線路，度過美好的一天。我們感謝您今天的參與。