Axsome Therapeutics Inc (AXSM) 2022 Q4 法說會逐字稿

Good morning, and welcome to the Axsome Therapeutics Conference Call. (Operator Instructions) As a reminder, today's conference is being recorded. I would now like to turn the conference over to your host, Mark Jacobson, Chief Operating Officer at Axsome Therapeutics. Please go ahead.

早上好，歡迎來到 Axsome Therapeutics 電話會議。 （操作員說明）提醒一下，今天的會議正在錄製中。我現在想把會議轉交給你的主持人，Axsome Therapeutics 的首席運營官 Mark Jacobson。請繼續。

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 full year and the fourth quarter of 2022.

謝謝你，運營商。早上好，感謝大家參加今天的電話會議。今天上午，我們發布了收益新聞稿，提供了公司最新情況以及公司全年和 2022 年第四季度財務業績的詳細信息。

The release crossed the wire a short time ago and is available on our website at axsome.com. 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.

該版本不久前發布，可在我們的網站 axsome.com 上獲取。在今天的電話會議中，我們將做出某些前瞻性陳述。這些聲明可能包括關於我們研究藥物的有效性、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、未來臨床試驗來源的預期行為、監管計劃等方面的聲明、未來的研發計劃、我們關於 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 use 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可能發生變化的當前信息、假設和預期，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定期向美國證券交易委員會提交的文件中有所描述，包括我們的季度和年度報告。請注意不要過分依賴前瞻性聲明，這些聲明僅在今天發布，公司不承擔任何更新此類聲明的義務。

Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Lori Englebert, Executive Vice President of Commercial and Business Development. Herriot will first provide an overview of the company and then reveal progress made during 2022 and in the fourth quarter as well as upcoming milestones.

今天和我一起參加電話會議的是首席執行官 Herriot Tabuteau 博士；首席財務官 Nick Pizzie；商業和業務發展執行副總裁 Lori Englebert。 Herriot 將首先提供公司概況，然後揭示 2022 年和第四季度取得的進展以及即將到來的里程碑。

Following Herriot, Nick will review our financial results, and then Lori will provide a commercial update, including details on the first quarter of Auvelity, sales and our second quarter with Sunosi. We'll then open the line for questions. Questions will be taken in order they are received. And with that, I will turn the call over to Herriot.

在 Herriot 之後，Nick 將審查我們的財務業績，然後 Lori 將提供商業更新，包括 Auvelity 第一季度、銷售和我們與 Sunosi 的第二季度的詳細信息。然後我們將打開問題熱線。問題將按照收到的順序進行處理。有了這個，我會把電話轉給赫里奧特。

Well, thank you, Mark. Good morning, everyone, and thank you all for joining Axsome Therapeutics Year-end and Fourth Quarter 2022 Financial Results and Business Update Conference Call. 2022 was a transformative year for Axsome as we successfully transitioned to commercial stage and have delivered on our goal to become a leading CNS-focused biopharmaceutical company.

好吧，謝謝你，馬克。大家早上好，感謝大家參加 Axsome Therapeutics 年終和 2022 年第四季度財務業績和業務更新電話會議。 2022 年對 Axsome 來說是變革的一年，因為我們成功過渡到商業階段，並實現了成為領先的以中樞神經系統為重點的生物製藥公司的目標。

Now with 2 differentiated products, Auvelity and Sunosi commercialized, encouraging early launch metrics of Auvelity, abroad and advancing late-stage pipeline and a strong financial position, Axsome is well positioned to continue to deliver significant value to patients and shareholders.

現在，Auvelity 和 Sunosi 這兩種差異化產品已商業化，鼓勵 Auvelity 在國外的早期推出指標，並推進後期管道和強大的財務狀況，Axsome 有能力繼續為患者和股東創造重要價值。

The fourth quarter was an important milestone for Axsome, as it is the first quarter with sales for both Auvelity and Sunosi. Total net product sales in the quarter was strong at $24.4 million. Later, Nick and Lori will provide further details on our financial and commercial performance.

第四季度對 Axsome 來說是一個重要的里程碑，因為這是 Auvelity 和 Sunosi 均實現銷售的第一季度。本季度產品淨銷售額總額為 2440 萬美元，表現強勁。稍後，Nick 和 Lori 將提供有關我們財務和商業業績的更多詳細信息。

To Auvelity updates, I'd like to start by taking -- by talking about the topic that brings us all here, which is making a difference for patients. In just more than a quarter, Auvelity has already been prescribed to thousands of patients and we have seen repeat prescribing by HCPs and refills by patients.

對於 Auvelity 的更新，我想首先談一談將我們所有人帶到這裡的話題，這對患者產生了影響。在僅僅四分之一多的時間裡，Auvelity 已經被開給了數千名患者，我們已經看到 HCP 重複開藥和患者重新配藥。

Lori will provide additional perspective later. But the operations suggest that the unique mechanistic and clinical profile of Auvelity is having a positive impact on the treatment landscape for major depressive disorder and making a meaningful difference to the lives of MDD patients.

Lori 稍後將提供更多觀點。但這些操作表明，Auvelity 獨特的機制和臨床特徵正在對重度抑鬱症的治療前景產生積極影響，並對 MDD 患者的生活產生有意義的影響。

Furthermore, with just half a year of Sunosi sales at the Axsome relaunch efforts, we've seen sale growth both in the U.S. and overseas. We view the potential fortunate in the current indication is largely contact leading room for significant potential for future growth.

此外，隨著 Axsome 重新啟動努力的 Sunosi 銷售僅半年，我們已經看到美國和海外的銷售增長。我們認為目前的跡象表明潛在的幸運在很大程度上是接觸領先的未來增長潛力的巨大空間。

Just last week, we announced an important licensing deal providing our new partner commercial rights to Sunosi in Europe and certain countries in the Middle East and North Africa.

就在上週，我們宣布了一項重要的許可協議，向歐洲的 Sunosi 以及中東和北非的某些國家/地區提供我們的新合作夥伴商業權利。

(inaudible) share our excitement and commitment to maximize the potential of Sunosi for patients worldwide. Their strong commercial platform is well suited to expand the availability of an access for this important treatment in the licensed region. In addition to our financial progress, our broad late-stage CNS pipeline continues to advance, positioning us to drive further significant value creation in 2023 and beyond.

（聽不清）分享我們的興奮和承諾，以最大限度地發揮 Sunosi 對全球患者的潛力。他們強大的商業平台非常適合在許可地區擴大這種重要治療的可及性。除了我們的財務進展外，我們廣泛的後期 CNS 管線也在繼續推進，使我們能夠在 2023 年及以後推動進一步顯著的價值創造。

Our leading CNS pipeline includes AXS-07 for migraine, AXS-05 for agitation and for smoking cessation, AXS-12 for narcolepsy, AXS-14 for fibromyalgia and Solriamfetol for ADHD.

我們領先的中樞神經系統管線包括用於偏頭痛的 AXS-07、用於躁動和戒菸的 AXS-05、用於嗜睡症的 AXS-12、用於纖維肌痛的 AXS-14 和用於 ADHD 的 Solriamfetol。

In the fourth quarter and subsequently, we made significant progress in our disease agitation program AXS-05 including the announcement of positive top line results from the ACCORD trial, advanced on the ADVANCE-2 trial and obtaining FDA feedback on our development plan for AXS-05 in AD agitation.

在第四季度及隨後，我們在我們的疾病激越計劃 AXS-05 中取得了重大進展，包括宣布 ACCORD 試驗的積極頂線結果、推進 ADVANCE-2 試驗並獲得 FDA 對我們的 AXS-開發計劃的反饋- 05年AD風波。

With regards to ADVANCE-2, our parallel group trial, based on current enrollment trends, we now anticipate completion of this trial in the first half of 2024 versus our prior guidance of mid-2025.

關於 ADVANCE-2，我們的平行組試驗，根據當前的註冊趨勢，我們現在預計該試驗將在 2024 年上半年完成，而我們之前的指導是在 2025 年年中。

Given all the progress in all times disease agitation program, we're recently sought and received feedback from the FDA on the registration plan. The FDA requested generation of additional safety experience with AXS-05 in the targeted population, including placebo-controlled safety information from the ongoing ADVANCE-2 trial as well as long-term safety data in the target patient population consistent with ICH E1 guidelines.

鑑於所有時間疾病激越計劃的所有進展，我們最近尋求並收到了 FDA 對註冊計劃的反饋。 FDA 要求在目標人群中產生額外的 AXS-05 安全經驗，包括來自正在進行的 ADVANCE-2 試驗的安慰劑對照安全信息，以及目標患者人群中符合 ICH E1 指南的長期安全數據。

Based on this feedback, the company intends to submit an NDA for AXS-05 after completion of the ongoing ADVANCE-2 and open-label safety extension trials.

基於這一反饋，該公司打算在完成正在進行的 ADVANCE-2和開放標籤安全擴展試驗後提交 AXS-05的 NDA 。

In parallel, we expect to initiate a Phase II/III trial of AXS-05 in smoking cessation in the fourth quarter of 2023. With regards to AXS-07 for the acute treatment of migraine, manufacturing activities related to the resubmission of the NDA for this product candidate are ongoing, and we expect the resubmission to occur in the second half of this year.

同時，我們預計將在 2023 年第四季度啟動 AXS-05 戒菸的 II / III 期試驗。關於 AXS-07 用於急性偏頭痛治療，與重新提交 NDA 相關的製造活動該候選產品正在進行中，我們預計將在今年下半年重新提交。

AXS-12, our product candidate for the treatment of narcolepsy enrollment in the pivotal Phase III SYMPHONY trial is progressing, and top line results are expected in the first half of 2023.

AXS-12是我們在關鍵的 III 期 SYMPHONY 試驗中治療發作性睡病的候選產品，目前正在取得進展，預計將在 2023 年上半年取得一線成果。

As a reminder, AXS-12 has been granted orphan drug designation by the FDA for the treatment of narcolepsy. Our AXS-14 product candidate for fibromyalgia is also progressing with manufacturing and other activities related to the preparation of planned NDA submission ongoing, and we expect to submit the NDA for product candidate in 2023.

提醒一下，AXS-12 已被 FDA 授予孤兒藥資格，用於治療發作性睡病。我們用於纖維肌痛的 AXS-14 候選產品也在製造和其他與準備計劃的 NDA 提交相關的活動中取得進展，我們預計將在 2023 年提交候選產品的 NDA。

With regard for Sunosi for the treatment of ADHD, we are preparing to initiate a Phase III trial in this indication in the first half of 2023. In the fourth quarter, we also shared positive top line results from the SHARP trial, demonstrating improving the cognitive function with solid treatment and highlighted new mechanistic data for all the (inaudible).

關於用於治療多動症的 Sunosi，我們準備在 2023 年上半年啟動針對該適應症的 III 期試驗。在第四季度，我們還分享了 SHARP 試驗的積極頂線結果，證明改善了認知能力具有堅固處理的功能，並突出顯示所有（聽不清）的新機械數據。

These results further highlight the clinical potential and differentiated pharmacology of this molecule. As you can see, the Axsome team is busy and continues to be excited as we prepare to deliver ongoing commercial success and potentially hit on multiple pipeline milestones, including clinical trial readouts and initiations and NDA filings in the next 12 to 18 months.

這些結果進一步突出了該分子的臨床潛力和差異化藥理學。正如您所看到的，Axsome 團隊很忙，並且繼續感到興奮，因為我們準備取得持續的商業成功，並可能在未來 12 到 18 個月內實現多個管道里程碑，包括臨床試驗讀數和啟動以及 NDA 備案。

I will now turn the call over to Nick, who will review our financial results.

我現在將電話轉給尼克，他將審查我們的財務業績。

Thank you, Herriot, and good morning, everyone. Today, I'll discuss our fourth quarter and full year results and provide some financial guidance. Total revenue in the fourth quarter of '22 was $24.4 million, consisting of net sales of our 2 commercialized products of Auvelity and Sunosi. There were no net sales in the comparable prior period. Auvelity was launched in the fourth quarter on October '19, and for the partial quarter generated net sales of $5.2 million.

謝謝你，赫里奧特，大家早上好。今天，我將討論我們的第四季度和全年業績，並提供一些財務指導。 22 年第四季度的總收入為 2440 萬美元，其中包括我們的 Auvelity 和 Sunosi 兩種商業化產品的淨銷售額。可比前期沒有淨銷售額。 Auvelity 於 2019 年 10 月第四季度推出，部分季度產生了 520 萬美元的淨銷售額。

Sunosi generated total net sales to Axsome of $19.2 million in the fourth quarter, consisting of U.S. net sales of $18.3 million and international net sales of $900,000. Because the ex U.S. acquisition of Sunosi closed on November 14, the reported international net sales reflect the first quarter.

Sunosi 第四季度為 Axsome 帶來的總淨銷售額為 1,920 萬美元，其中美國淨銷售額為 1,830 萬美元，國際淨銷售額為 900,000 美元。由於美國前對 Sunosi 的收購於 11 月 14 日結束，因此報告的國際淨銷售額反映了第一季度的情況。

Total revenue for the full year of 2020 was $50 million.

2020 年全年總收入為 5000 萬美元。

Again, there were no reported sales for the prior year because of the acquisition of Sunosi and the launch of Auvelity both occurred in '22. For the full year of 2022, Auvelity net sales were $5.2 million. For the full year 2022, Sunosi generated total net sales to Axsome of $44.8 million, consisting of U.S. net sales of $43.9 million and international net sales of $900,000.

同樣，由於對 Sunosi 的收購和 Auvelity 的推出都發生在 22 年，因此沒有報告上一年的銷售額。 2022年全年，Auvelity淨銷售額為520萬美元。 2022年全年， Sunosi 為 Axsome 帶來的總淨銷售額為4480萬美元，其中美國淨銷售額為4390萬美元，國際淨銷售額為90萬美元。

As a reminder, the U.S. portion of the acquisition of Sunosi was completed on May 9. Cost of product sales were $2.3 million and $5.2 million for the fourth quarter and full year of 2022, respectively, compared to none in the prior year.

提醒一下，對 Sunosi 的美國部分收購已於 5 月 9 日完成。2022 年第四季度和全年的產品銷售成本分別為 230 萬美元和 520 萬美元，而去年同期為零。

Research and development expenses were $14.7 million and $57.9 million for the fourth quarter and full year 2022, respectively, and $13.8 million and $58.1 million for the comparable period in 2021. The increase for the fourth quarter was primarily related to higher costs associated with ongoing clinical trials including post-marketing commitments for Sunosi and Auvelity.

2022 年第四季度和全年的研發費用分別為 1,470 萬美元和 5,790 萬美元，2021 年同期為 1,380 萬美元和 5,810 萬美元。第四季度的增加主要與正在進行的臨床試驗相關的成本增加有關試驗包括 Sunosi 和 Auvelity 的上市後承諾。

Selling, general and administrative expenses were $61.5 million and $159.3 million for the fourth quarter and full year of 2022, respectively, and $18.8 million and $66.6 million for the comparable period in 2021. The increases for the fourth quarter and full year were primarily related to commercial activities for Sunosi and Auvelity, including sales force onboarding, marketing spend as well as higher noncash stock compensation expense.

2022 年第四季度和全年的銷售、一般和管理費用分別為 6150 萬美元和 1.593 億美元，2021 年同期分別為 1880 萬美元和 6660 萬美元。第四季度和全年的增長主要與Sunosi 和 Auvelity 的商業活動，包括銷售人員入職、營銷支出以及更高的非現金股票補償費用。

Net loss for the fourth quarter of 2022 was $61.2 million or $1.41 per share compared to a net loss of $34 million or $0.90 per share for the comparable period in 2021. The net loss for the fourth quarter included $10.8 million of noncash stock compensation expense compared to $5.9 million in the comparable period in 2021.

2022 年第四季度淨虧損為 6120 萬美元或每股 1.41 美元，而 2021 年同期淨虧損為 3400 萬美元或每股 0.90 美元。第四季度淨虧損包括 1080 萬美元的非現金股票補償費用，相比之下到 2021 年同期的 590 萬美元。

Net loss was $187.1 million or $4.60 per share for the full year of 2022 compared to a net loss of $130.4 million or $3.47 per share for the comparable period in 2021. The net loss for the full year of 2022 included $37.7 million of noncash stock compensation expense compared to $20.8 million for the full year of 2021. We ended the year with $201 million in cash and equivalents compared to $86.5 million as of December 31, 2021.

2022 年全年淨虧損為 1.871 億美元或每股 4.60 美元，而 2021 年同期淨虧損為 1.304 億美元或每股 3.47 美元。2022 年全年淨虧損包括 3770 萬美元的非現金股票補償與 2021 年全年的 2080 萬美元相比，我們的支出為 2.01 億美元，而截至 2021 年 12 月 31 日為 8650 萬美元。

During the fourth 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 and interest-only periods while accessing a $55 million tranche.

在第四季度，我們沒有使用我們的 ATM 設施。 2023 年 1 月，我們修改了與 Hercules Capital 的貸款協議，將貸款規模增加到 3.5 億美元，以降低利率並延長到期日和只付息期，同時獲得 5500 萬美元的貸款。

Additionally, in February 2023, the company received approximately $66 million from the out-licensing of ex U.S. Sunosi rights. Inclusive of these events, our pro forma year-end cash balance now exceeds $300 million. We believe that our current cash balance, along with 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.

此外，在 2023 年 2 月，該公司從前美國 Sunosi 權利的對外許可中獲得了約 6600 萬美元。包括這些事件在內，我們的備考年終現金餘額現已超過 3 億美元。我們認為，根據我們目前的運營計劃，我們目前的現金餘額，以及來自 Hercules Capital 的 3.5 億美元定期貸款額度的剩余承諾資本，足以為預期的運營提供資金，使現金流為正。

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

我現在將電話轉給 Lori，他將提供商業更新。

Thank you, Nick. Q4 was certainly an exciting quarter for Axsome with the launch of Auvelity and the continued relaunch of Sunosi. Both of our commercial products address serious, highly prevalent conditions and bring meaningful innovation to millions with potential patients.

謝謝你，尼克。隨著 Auvelity 的推出和 Sunosi 的持續重啟，第四季度對於 Axsome 來說無疑是一個令人興奮的季度。我們的兩種商業產品都解決了嚴重、高度流行的情況，並為數百萬潛在患者帶來了有意義的創新。

We are pleased with our commercial progress on Sunosi. And although it is still early days, we are encouraged by Auvelity launch progress. I will share our key metrics from our commercial efforts for both brands, starting with Sunosi followed by Auvelity.

我們對 Sunosi 的商業進展感到滿意。儘管現在還處於早期階段，但我們對 Auvelity 的發布進展感到鼓舞。我將分享我們對這兩個品牌的商業努力的關鍵指標，首先是 Sunosi，然後是 Auvelity。

As a reminder, Sunosi is the first and only the DNRI for excessive daytime sleepiness and obstructive sleep apnea and narcolepsy and the first and only weight-promoting agent driven to improve weight through 9 hours. In the fourth quarter, total prescriptions for Sunosi in the U.S. grew 11% year-over-year and 1% quarter-over-quarter.

提醒一下，Sunosi 是第一個也是唯一一個針對白天過度嗜睡、阻塞性睡眠呼吸暫停和發作性睡病的 DNRI，也是第一個也是唯一一個在 9 小時內推動體重改善的體重促進劑。第四季度，美國 Sunosi 的總處方量同比增長 11%，環比增長 1%。

For the full year 2022, U.S. total Sunosi prescriptions showed strong growth with an increase of 21% versus 2021. The total prescription split by the diagnosed patient population for Sunosi is 70% for EDS due to and 30% for EDS due to narcolepsy. Payer coverage for Sunosi remains broad with 96% of commercial lives and 83% of total lives covered. The growth potential for Sunosi in the currently approved indication remains substantial. Sunosi currently has only a 2% share of drug-treated OSA patients and a 7% share in drug-treated narcolepsy patients.

到 2022 年全年，美國的 Sunosi 處方總量顯示出強勁增長，與 2021 年相比增長了 21%。Sunosi 診斷患者人群的總處方分配為 70% 的 EDS 和 30% 的 EDS 由於發作性睡病。 Sunosi 的付款人覆蓋範圍仍然很廣，覆蓋了 96% 的商業生命和 83% 的總生命。 Sunosi 在目前批准的適應症中的增長潛力仍然很大。 Sunosi 目前在接受藥物治療的 OSA 患者中僅佔 2% 的份額，在接受藥物治療的發作性睡病患者中僅佔 7% 的份額。

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

Sunosi 是唯一可用於患有 EDS 和 OSA 的患者的品牌療法，我們預計將增加和加強宣傳和疾病教育工作，以推動該產品在 2023 年在美國的市場份額增長。

With recently announced licensing of ex U.S. marketing rights for Sunosi to Pharmanovia, we are well positioned to increase the availability of the treatment to patients worldwide.

隨著最近宣布將 Sunosi 的美國前營銷權授權給 Pharmanovia，我們處於有利地位，可以增加全球患者的治療可用性。

Turning to Auvelity. We launched Auvelity on October 19 and despite launching in Q4, a traditionally challenging quarter due to multiple holidays. We saw early signs of encouraging uptake with our initial HCP adopters.

轉向 Auvelity。我們於 10 月 19 日推出了 Auvelity，儘管在第 4 季度推出，由於多個假期，這是一個傳統上具有挑戰性的季度。我們在最初的 HCP 採納者中看到了鼓勵採用的早期跡象。

With only 10 full weeks of promotion in Q4, 2,200 unique HCPs were prescriptions for over 6,000 new patients. Those metrics have grown to 4,300 unique HCP writers and over 13,700 new patients since launch. Importantly, HCPs who have written ability are gaining credible early clinical experience and are reporting promising patient response that is consistent with that with what we saw in clinical trials with many reportedly seen rapid onset of action and rapid achievement of our mission.

僅在第 4 季度整整 10 週的促銷活動中，就有 2,200 名獨特的 HCP 為超過 6,000 名新患者開了處方。自推出以來，這些指標已增長到 4,300 名獨特的 HCP 作者和超過 13,700 名新患者。重要的是，具有書面能力的 HCP 正在獲得可靠的早期臨床經驗，並報告了有希望的患者反應，這與我們在臨床試驗中看到的結果一致，據報導許多人看到了快速開始行動和快速完成我們的使命。

With regard to payer coverage, the commercial channel is expected to be the primary channel for Auvelity as it accounts for more than 60% of antidepressive prescription volume.

在支付方覆蓋方面，商業渠道預計將成為 Auvelity 的主要渠道，因為它佔抗抑鬱藥處方量的 60% 以上。

Interactions with commercial payers as it relates to Auvelity have been active and productive. Effective January 2023, we have contracted with one of the largest group purchasing organizations, or GPOs, for potential coverage of Auvelity.

與 Auvelity 相關的商業付款人的互動是積極和富有成效的。自 2023 年 1 月起，我們已與最大的集團採購組織 (GPO) 之一簽訂合同，以潛在覆蓋 Auvelity。

As a result, pharmacy benefit managers or PBMs and health plans under the GPO will now be able to make formulary coverage decisions for ability based on the contracted terms. These interactions with commercial payers are proceeding as expected during the standard 6- to 9-month period post launch when new drugs are blocked, while coverage decisions are being made.

因此，GPO 下的藥房福利經理或 PBM 和健康計劃現在將能夠根據合同條款為能力做出處方集承保決定。這些與商業付款人的互動在新藥上市後的標準 6 至 9 個月期間按預期進行，此時新藥被阻止，同時正在做出承保決定。

In the noncommercial channel, Medicaid coverage became effective in 49 states on January 1, and Medicare plans have up to 6 months post launch to determine coverage and ad ability to formulary. We expect additional formulary decisions over the next 6 months. I look forward to discussing more as the payer process progresses. We are extremely encouraged by the initial launch progress and remain committed to our launch focus of driving fast HCP adoption, empowering patients and enabling quality access.

在非商業渠道，醫療補助計劃於 1 月 1 日在 49 個州生效，醫療保險計劃在推出後最多有 6 個月的時間來確定處方集的覆蓋範圍和廣告能力。我們預計在接下來的 6 個月內會做出更多的處方決定。我期待著隨著付款流程的進展進行更多討論。我們對最初的啟動進展感到非常鼓舞，並將繼續致力於我們的啟動重點，即推動 HCP 的快速採用、賦予患者權力和實現高質量的訪問。

We are all aware that there is a mental health crisis happening in the U.S. and major depressive disorder, or MDD, is a major public health concern with 21 million U.S. adults diagnosed in 2020 and reported a significant increase in prevalence as a result of the pandemic.

我們都知道，美國正在發生精神健康危機，重度抑鬱症 (MDD) 是一個主要的公共衛生問題，2020 年有 2100 萬美國成年人被診斷出患有抑鬱症，並且據報導，由於大流行，患病率顯著增加.

Mobility is an important new therapeutic option for patients living with this chronic and devastating condition and we are proud of our efforts to make ability available to patients living with MDD and their physicians.

對於患有這種慢性和破壞性疾病的患者來說，流動性是一種重要的新治療選擇，我們為我們為患有 MDD 的患者及其醫生提供能力而做出的努力感到自豪。

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

我現在將把電話轉回給馬克來主持問答討論。

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

偉大的。謝謝你，洛瑞。接線員，我們可以問第一個問題嗎？

Yes. Our first question is from Charles Duncan with Cantor Fitzgerald.

是的。我們的第一個問題來自 Charles Duncan 和 Cantor Fitzgerald。

Yes. Thanks, Herriot, and team for that great overview and congrats on the good quarter. I had a couple of questions on Auvelity. One is commercial. One is more development. And that is regarding the commercial question. I'm just kind of wondering, I think what Lori just said, addresses this question, but I'm wondering if you could drill down on any feedback she's getting from the market in terms of response rates and even persistence, and I know it's too long or too early to know a real persistence, but what are prescribers seeing in their patients with regard to comparison in patients who are experienced with SSRI-based therapy?

是的。謝謝 Herriot 和團隊的精彩概述，並祝賀這個季度的好成績。我有幾個關於 Auvelity 的問題。一種是商業性的。一是更加發展。那是關於商業問題的。我只是有點想知道，我認為 Lori 剛才所說的解決了這個問題，但我想知道你是否可以深入了解她從市場獲得的任何反饋，包括響應率甚至持久性，我知道這是太久或太早無法了解真正的持久性，但開處方者在與接受過 SSRI 療法的患者進行比較時，在他們的患者身上看到了什麼？

Charles, thanks for the question, and good morning. So again, you're right, very early days for us. And most of what we're receiving back from the field is purely anecdotal. So I hope you take for what it's worth.

查爾斯，謝謝你的提問，早上好。所以，你是對的，對我們來說還很早。我們從現場收到的大部分信息純粹是軼事。所以我希望你物有所值。

What we are hearing anecdotally is that patients are responding very consistent to label. So that rapid onset of action is happening. They are seeing very early achievement of remission. Again, it's a little bit too early to talk about their ability because we're just a few months into launch, but we've not seen anything that would suspect -- we expect would be different than what we see in the label or what we saw in the clinical trials.

我們聽到的傳聞是，患者對標籤的反應非常一致。因此，正在迅速採取行動。他們很早就看到了緩解。同樣，現在談論他們的能力還為時過早，因為我們剛剛推出幾個月，但我們還沒有看到任何值得懷疑的東西——我們預計會與我們在標籤中看到的或其他東西不同我們在臨床試驗中看到了。

And maybe to add to that, I think one of the things that we are seeing or repeat prescriptions. So patients are prescriptions they would have been switched off with those in persistence.

也許除此之外，我認為我們正在看到或重複處方的事情之一。因此，患者是處方藥，他們本來會被那些堅持不懈的人關掉的。

Exactly. And just to give you some additional color there, last week's reported data, about 50% of the scrips were for refills.

確切地。只是為了給你一些額外的顏色，上週報告的數據，大約 50% 的紙條用於補充。

Okay. That's great to hear. Regarding TAM extension efforts for 005 in Alzheimer's agitation, Herriot you mentioned some feedback from agency, I wasn't completely clear on that in terms of timing. I think that you mentioned possibly completing the trial in '24 versus prior '25, if you could provide more color on that?

好的。聽到這個消息我很高興。關於 005 在阿爾茨海默氏症激動中的 TAM 擴展工作，赫里奧特你提到了機構的一些反饋，我在時間方面並不完全清楚。我認為你提到可能在 24 年完成試驗而不是之前的 25 年，如果你能提供更多的顏色？

And then explicitly, you thought an NDA would happen after advance to but then also after an open-label extension study. So could you give us a sense of timing on when an NDA could be filed?

然後明確地說，你認為 NDA 會在推進到開放標籤擴展研究之後發生。那麼，您能否告訴我們何時可以提交保密協議？

Thanks a follow-up question, Charles. With regards to our disease of agitation trial, you're correct. So based on the fact that enrollment is going to be, frankly, faster than we had expected. We now expect for that study to read out first half of 2024. The open-label extension trial has been ongoing, and we would also expect that to read out in 2024. And with regards to filing, we would be in a position to file an NDA within 6 months after the readout of those studies.

感謝後續問題，查爾斯。關於我們的躁動症試驗，你是對的。因此，坦率地說，基於註冊速度比我們預期更快的事實。我們現在預計該研究將在 2024 年上半年宣讀。開放標籤擴展試驗一直在進行中，我們也希望在 2024 年宣讀。關於備案，我們將能夠提交在讀出這些研究後 6 個月內提交 NDA。

Our next question comes from the line of Marc Goodman with SVB.

我們的下一個問題來自 SVB 的 Marc Goodman。

Herriot, just to continue on this agitation study. Can you confirm like your discussions with FDA? Have they signed off on both studies from an efficacy standpoint and all we're waiting for now is the safety data? Can you just confirm that? And second question is, if you all can help us with how to think about gross to nets for both products for this year?

赫里奧特，只是為了繼續這項激動人心的研究。你能確認你與 FDA 的討論嗎？他們是否從療效的角度簽署了這兩項研究，我們現在等待的只是安全數據？你能確認一下嗎？第二個問題是，如果你們都可以幫助我們如何考慮今年這兩種產品的淨收入？

Thanks for the question, Charles.

謝謝你的問題，查爾斯。

Marc.

馬克。

I'm sorry, Marc. Oh my God, all these sell-side analysts are starting with blur into 1. No, of course not. All of you are very distinct. So Marc, the -- with regards to the interactions with FDA, we saw feedback on the trials.

對不起，馬克。天哪，所有這些賣方分析師都是從 blur into 1 開始的。不，當然不是。你們都很與眾不同。所以馬克，關於與 FDA 的互動，我們看到了對試驗的反饋。

The feedback that we got from the agency is that in the elderly patient population, safety is really important, not just long-term safety data, but also the placebo-controlled safety data. So the ACCORD trial, it was a randomized controlled study. So it does not provide the randomized safety data, which the is really important in this patient population.

我們從該機構得到的反饋是，在老年患者群體中，安全性非常重要，不僅是長期安全性數據，還有安慰劑對照的安全性數據。所以 ACCORD 試驗是一項隨機對照研究。所以它不提供隨機安全數據，這在這個患者群體中非常重要。

And the other aspect of the study did highlight not necessarily show-stopper, is the fact that this was a truncated study. So -- and importantly though, the feedback with regards to exact patient numbers for database is that it must meet ICH E1 guidelines.

而該研究的另一個方面確實強調了不一定是展示塞子，這是一個被截斷的研究。所以——但重要的是，關於數據庫確切患者數量的反饋是它必須符合 ICH E1 指南。

So what's good is we're in a good position to provide actually all of those data points to the FDA, we do have the ADVANCE-1 trial, which is already ongoing, which is enrolling and so -- I'm sorry, the ADVANCE-2 trial, which is already enrolling. And so we're in a good position to provide all the safety data which would be required for the NDA filing.

所以好的是我們能夠向 FDA 提供實際上所有這些數據點，我們確實有 ADVANCE-1 試驗，該試驗已經在進行中，正在招募中，所以——對不起， ADVANCE-2 試驗，已經在招募中。因此，我們可以很好地提供 NDA 備案所需的所有安全數據。

Herriot, if ADVANCE-2 fails from an efficacy standpoint then what?

Herriot，如果 ADVANCE-2 從功效的角度來看失敗了，那該怎麼辦？

Well, that would be speculation. But we are encouraged that we currently have 2 positive trials in this indication.

好吧，那隻是猜測。但令我們感到鼓舞的是，我們目前在該適應症方面有 2 項陽性試驗。

Right. That's my question, did the FDA agree that you have 2 positive trials?

正確的。那是我的問題，FDA 是否同意你們有 2 項陽性試驗？

The FDA never read anything until you file an NDA and they review it. But it's very clear that we did have 2 positive trials very core buyback. And we track to reline safety information that will be needed for an NDA filing.

在您提交 NDA 並對其進行審查之前，FDA 永遠不會閱讀任何內容。但很明顯，我們確實進行了 2 次非常核心的積極回購試驗。我們跟踪重新排列 NDA 備案所需的安全信息。

Okay. And then the gross to nets for both products for this year, how do we think about that?

好的。然後是今年這兩種產品的淨利潤，我們如何看待？

Yes, sure. Marc, it's Nick. For gross to net, so for the quarter for Auvelity, I'll start with, gross net for the quarter was in the 60s. As of right now, we're not currently in a position to give specific guidance around GTN. However, we remind you that there's no reason to expect that's actually going to improve from this quarter and then obviously, could potentially worsen based on Q1 being typical -- the seasonality that you expect a typical headwinds of plant coverages resetting in year, inclusive of deductibles, coinsurance, PAs would need to be in some plans would need to be recreated again. So potential utilization, higher utilization of the co-pay card.

是的，當然。馬克，是尼克。對於毛淨值，所以對於 Auvelity 的季度，我將開始，該季度的毛淨值在 60 年代。截至目前，我們目前無法就 GTN 提供具體指導。但是，我們提醒您，沒有理由期望從本季度開始實際情況會有所改善，然後顯然，根據第一季度的典型情況，可能會惡化——您預計一年中工廠覆蓋率會出現典型逆風的季節性，包括免賠額、共同保險、PA 需要在某些計劃中需要重新創建。所以潛在的利用率，共同支付卡的利用率更高。

And then obviously, mix and channel distribution always impacts GTN. So we would expect in Q1 and Q2 that we wouldn't expect anything better than where we were at today and potentially it could worsen.

然後很明顯，混合和渠道分配總是影響 GTN。因此，我們預計第一季度和第二季度的情況不會比今天更好，而且可能會惡化。

Specifically around Sunosi. Sunosi, we were in the low 50s. Again, for this quarter, we did have a favorable adjustment from the prior quarters of $1.8 million. The GTN adjustment as we received updated claims, which is typical that we received them in this quarter. Otherwise, for Sunosi, it's pretty much been stable in the low 50s.

特別是在 Sunosi 周圍。 Sunosi，我們還不到 50 歲。同樣，對於本季度，我們確實比前幾個季度進行了 180 萬美元的有利調整。我們收到更新的索賠時的 GTN 調整，這是我們在本季度收到的典型情況。否則，對於 Sunosi 來說，它在 50 年代的低位幾乎保持穩定。

Our next question is from the line of Vikram Purohit with Morgan Stanley.

我們的下一個問題來自 Vikram Purohit 與摩根士丹利的合作。

So we had 2 on Auvelity. So first, just wondering if you could provide some color on kind of the typical profile of patients that are currently receiving Auvelity terms of the prior treatment history and the lines of therapy that have been on prior to being prescribed Auvelity?

所以我們在 Auvelity 上有 2 個。所以首先，只是想知道您是否可以提供一些關於目前正在接受先前治療史的 Auvelity 條款的患者典型特徵的顏色，以及在開出 Auvelity 之前已經接受的治療線？

And then secondly, I just wanted to see if you could provide an update on ex U.S. commercialization and partnership discussions if those have been happening. And if so, what you'd be looking for in a potential partner for AXS-05 ex U.S.?

其次，我只是想看看您是否可以提供有關前美國商業化和合作夥伴關係討論的最新情況，如果這些已經發生的話。如果是這樣，您在 AXS-05 ex U.S. 的潛在合作夥伴中尋找什麼？

Vikram, I'll take that. So currently, as we've mentioned multiple in and as the standard, most of the commercial plans have ability in block as requires quite an effort to get patients online, which is why we're really excited about the demand that we're driving despite these challenges.

維克拉姆，我會接受的。因此，目前，正如我們提到的那樣，作為標準，大多數商業計劃都具有區塊能力，因為需要付出相當大的努力才能讓患者上網，這就是為什麼我們對我們正在推動的需求感到非常興奮儘管有這些挑戰。

However, due to that, therapy use has been relatively later line right now with about 28% sitting in second line and 61% sitting in third line-plus. The response has been, again, to the question I answered with Charles, the response has been very, very consistent with label. And to see that in later line patients is extremely encouraging.

然而，正因為如此，目前治療的使用相對較晚，大約 28% 的人坐在二線，61% 的人坐在三線以上。回應再次是針對我與 Charles 一起回答的問題，回應與標籤非常、非常一致。並且在後線患者中看到這一點非常令人鼓舞。

Just with regards to the second part of your question as it relates to what we would be looking for with regards to a potential partner for Auvelity in ex U.S. I think one of the things that we would look for is a partner with proven capabilities but also a partner that has experienced with regards to navigating the pretty complex reimbursement landscape in certain geographies such as Europe.

關於你問題的第二部分，因為它與我們在前美國尋找 Auvelity 的潛在合作夥伴有關。一位在處理某些地區（例如歐洲）相當複雜的報銷環境方面經驗豐富的合作夥伴。

The next question is from the line of Jason Gerberry with Bank of America.

下一個問題來自美國銀行的 Jason Gerberry。

Are you guys planning to increase enrollment of ADVANCE-2 to get to the 300 patients by 6 months? I was just doing the math on, I think, what, 50 patients from ACCORD went into randomized withdrawal, and then you have 175 under the current enrollment plan for ADVANCE-2. So just curious how you get to the 300?

你們是否計劃增加 ADVANCE-2 的註冊人數以在 6 個月前達到 300 名患者？我只是在做數學，我想，有 50 名來自 ACCORD 的患者隨機退出，然後根據當前的 ADVANCE-2 註冊計劃有 175 名患者。所以很好奇你是如何達到 300 的？

And then if you can comment on how we should be thinking about SG&A and OpEx ramp is 4Q 2022 on an annualized basis, sort of a good place to think about some growth off of that number or is there going to be any step-up from there? And then just last question? Any comments on any inventory launch stocking here on the fourth quarter number.

然後，如果您可以評論我們應該如何考慮 SG&A 和 OpEx 增長是按年化計算的 2022 年第四季度，這是一個考慮該數字增長的好地方，或者是否會有任何提升那裡？然後只是最後一個問題？關於第四季度數量的任何庫存發布庫存的任何評論。

I'll take first question, and Nick will take the others. The answer is no, we do not anticipate having to increase enrollment in ADVANCE-2 to reach the required patient safety database. As a reminder, we do have patients from ADVANCE-1, in terms of general safety experience, but then we also have 170 patients, as a reminder, who were enrolled in pivot 1 of ACCORD trial and a lot of those patients and most of those patients went into open-label safety extension trial. So if you take the patients rolling over from forward as well as the expected patients going over from ADVANCE-2 that should put us in pretty good shape.

我將回答第一個問題，尼克將回答其他問題。答案是否定的，我們預計不必增加 ADVANCE-2 的註冊人數即可達到所需的患者安全數據庫。提醒一下，就一般安全經驗而言，我們確實有來自 ADVANCE-1 的患者，但作為提醒，我們還有 170 名患者參加了 ACCORD 試驗的第 1 個關鍵點，其中很多患者和大多數患者這些患者進入了開放標籤安全擴展試驗。因此，如果您讓患者從前方翻身，以及預期的患者從 ADVANCE-2 翻身，那應該會讓我們處於非常好的狀態。

Sure. Jason, so related to OpEx guidance, I think like I think you mentioned using Q4 essentially as a proxy, I think that's a fair estimate. We stated in the press release that we expect expenses to increase year-over-year. Obviously, with the launch of Auvelity and Sunosi being acquired in the second quarter of this year, we'll have a full year of SG&A expenses and Q4 being almost a full quarter, I think you can expect you to use that as a proxy and potentially a modest growth from on the SG&A piece as it relates to thinking about 2023 on a quarterly basis.

當然。 Jason，與 OpEx 指導相關，我認為你提到使用 Q4 本質上作為代理，我認為這是一個公平的估計。我們在新聞稿中表示，我們預計支出將逐年增加。顯然，隨著今年第二季度收購 Auvelity 和 Sunosi 的推出，我們將有全年的 SG&A 費用，而第四季度幾乎是一個完整的季度，我認為你可以期望你將其用作代理和SG&A 部分可能會出現適度增長，因為它與按季度考慮 2023 年有關。

And then I think your other question broke up a little bit, but I think your question was related to inventory channel and where we were at the end of the year.

然後我認為你的另一個問題有點中斷，但我認為你的問題與庫存渠道以及我們在年底的位置有關。

For Auvelity, we have roughly 2.5 weeks of future demand in the channel. I think obviously, the growth brand, we just launched it, and we do expect inventory levels to fluctuate at our distributors as Auvelity builds additional momentum in the market.

對於 Auvelity，我們在渠道中有大約 2.5 週的未來需求。我認為很明顯，增長品牌，我們剛剛推出它，我們確實預計隨著 Auvelity 在市場上建立額外的動力，我們的分銷商的庫存水平會波動。

It's not unexpected, and we believe wearing patterns we really reflect the strong patient demand that we've seen. For Sunosi, we did have increased wholesale buying during -- due to the seasonality at the end of Q4. The inventory levels were somewhat elevated. However, we do see in Q1 that these inventory levels are coming down to approximately 2 to 2.5 weeks. And one note is that we are -- actually in Q1, we operationally for distribution, we changed our model from a Title Model to the traditional 3PL Model.

這並不出乎意料，而且我們相信佩戴方式確實反映了我們所看到的患者的強烈需求。對於 Sunosi，由於第四季度末的季節性，我們確實增加了批發採購。庫存水平有所上升。然而，我們確實在第一季度看到這些庫存水平正在下降到大約 2 到 2.5 週。需要注意的是，實際上在第一季度，我們在運營上進行分銷，我們將模型從 Title Model 更改為傳統的 3PL 模型。

That model was as it relates to -- as we launch and ensuring that we get licenses in every state. We changed to a traditional 3PL Model now and reduce the -- essentially the middle band distributor, so we will see an inventory reduction in the channel which will impact Q1 sales for Sunosi by roughly 2 weeks.

該模型與它相關 - 當我們啟動並確保我們在每個州獲得許可證時。我們現在改為傳統的 3PL 模型並減少 - 本質上是中間頻段分銷商，因此我們將看到渠道庫存減少，這將影響 Sunosi 第一季度的銷售額大約 2 週。

Our next question is from the line of David Amsellem with Piper Sandler.

我們的下一個問題來自 David Amsellem 和 Piper Sandler。

So just had a couple. First on Sunosi. Just broadly, what do you think you can do differently from the predecessor company that control the asset in terms of driving an inflection in volumes? And is the focus going to be more on OSA versus narcolepsy?

所以只有一對。首先是蘇諾西。從廣義上講，您認為在推動交易量變化方面，您可以做些什麼與控制資產的前身公司不同？重點是否會更多地放在 OSA 與發作性睡病上？

And just give us a sense of what you're prioritizing and how you believe the commercial landscape for Sunosi might prove to be different over time to the extent it is at all? So that's number one.

並且讓我們了解您的優先事項以及您如何相信隨著時間的推移，Sunosi 的商業前景可能會完全不同？所以這是第一。

And then number two, on Auvelity, how should we think about eventual expansion of the sales organization to the extent you need to and just talk about how that's going to evolve over time as the product gets more into its commercial life?

然後是第二，關於 Auvelity，我們應該如何考慮銷售組織的最終擴展到您需要的程度，並且只是談論隨著產品進入其商業生活，這將如何隨著時間的推移而演變？

Yes, David, I'll take both of those. So first of all, I'll start with Sunosi and how do we think we'll have an inflection point with this relaunch that we've talked about of Sunosi.

是的，大衛，我要這兩樣。所以首先，我將從 Sunosi 開始，我們如何看待我們已經談到的 Sunosi 的這次重新啟動會有一個轉折點。

Really strong foundation for the launch for the -- the initial launch. The important thing to remember about the initial launch with was that Jazz they launched about 3 months prior to the potent shutdowns. And so the initial launch was heavily impacted for the majority of the first 18 months of the launch for that product. What we believe we are doing right now that will help provide an inflection point is that we have gotten really hyper focused on the highest potential prescribers.

為首次發布奠定了堅實的基礎。關於首次發布，要記住的重要一點是，他們在強勢關閉前大約 3 個月發布了 Jazz。因此，在該產品發布的前 18 個月的大部分時間裡，首次發布受到了嚴重影響。我們相信我們現在正在做的有助於提供一個轉折點的是，我們已經真正高度關注最有潛力的處方者。

And our plan is to make sure that with our differentiated clinical profile that those 5 prescribers that we penetrate those prescribers and then start to expand out in terms of targets. Doing that will help us gain market share very quickly as we really get on the approach.

我們的計劃是確保憑藉我們差異化的臨床概況，我們滲透到這些處方者中的那 5 名處方者，然後開始在目標方面擴大。這樣做將幫助我們在真正採取行動時迅速獲得市場份額。

In terms of OSA versus narcolepsy. OSA has a prevalence of about 22 million patients and narcolepsy is 200,000. So that start difference right there tells you that a much larger opportunity is in OSA. We will, right now, continue to focus on other things, but we're not letting our foot off the (inaudible) on narcolepsy. So as there's still a lot of room for growth there as well.

在 OSA 與發作性睡病方面。 OSA 的患病率約為 2200 萬，發作性睡病為 200,000。因此，開始時的差異告訴您 OSA 中有更大的機會。現在，我們將繼續專注於其他事情，但我們不會放棄（聽不清）發作性睡病。因此，那裡還有很大的增長空間。

In terms of ability in the expanded sales organization, right now, we have about 165 reps coming on 25,000 HCPs. We are very, very confident in our -- using our DCC approach to make sure that our reps are able to have the tools that they need to make effective calls and be very efficient about doing it. And because of that, we are very focused on making sure the penetration in those original target list, which are the highest potential prescribers in the MDD space is really high before we comment any further on any additional plans.

就擴大後的銷售組織的能力而言，目前，我們有大約 165 名代表來自 25,000 名 HCP。我們對我們非常非常有信心 - 使用我們的 DCC 方法來確保我們的代表能夠擁有他們需要的工具來進行有效的呼叫並且非常有效地進行呼叫。正因為如此，在我們對任何其他計劃進行進一步評論之前，我們非常專注於確保那些原始目標列表中的滲透率非常高，這些原始目標列表是 MDD 領域中最有潛力的處方者。

Our next question is from the line of Joon Lee with Truist Securities.

我們的下一個問題來自 Truist Securities 的 Joon Lee。

In the press release, you mentioned potential for up to 4 NDAs over the next 12 to 18 months. I'm assuming that it also includes narcolepsy. And if so, is SYMPHONY and the Phase II sufficient to file? And I have a follow-up. .

在新聞稿中，您提到在未來 12 到 18 個月內可能會有多達 4 個 NDA。我假設它也包括發作性睡病。如果是這樣，SYMPHONY 和 Phase II 是否足以提交？我有一個後續行動。 .

Thank you for the question. Yes, we do believe that SYMPHONY and Phase II trial will be sufficient to file assuming that SYMPHONY is in progress stage.

感謝你的提問。是的，我們確實相信 SYMPHONY 和 II 期試驗足以提交，假設 SYMPHONY 處於進行中階段。

Great. And regarding the Sunosi deal, at a high level, it looks like you were able to monetize the European rights at a very attractive valuation, possibly more than what you had at for the worldwide rights, what do you think teams that allowed you to attract that value?

偉大的。關於 Sunosi 交易，從高層次上看，您似乎能夠以非常有吸引力的估值將歐洲版權貨幣化，可能比您對全球版權的估值更高，您認為允許您吸引的團隊是什麼那個值？

Well, I think that we've felt strongly about the potential for Sunosi and the overall value of the product. This transaction, the ex U.S. licensing it reflects the value of the product. So it's consistent with our perspective. What I start to a spin and what we communicated with regards to the potential of the product.

嗯，我認為我們對 Sunosi 的潛力和產品的整體價值有強烈的感覺。這筆交易，除美國許可外，它體現了產品的價值。所以這與我們的觀點是一致的。我開始討論的內容以及我們就產品潛力進行的交流。

Our next question is from the line of Joseph Thome with Cowen & Company.

我們的下一個問題來自 Cowen & Company 的 Joseph Thome。

Maybe the first one, just a clarification on the Auvelity number that you gave earlier, that 13,700 new patients was that as of last Friday or what was the cutoff date for that?

也許是第一個，只是對你之前提供的 Auvelity 數字的澄清，即 13,700 名新患者是截至上週五的數字，或者說截止日期是哪一天？

And then second was the -- we did see the NDA for (inaudible) on Auvelity. If you can just give us overall thoughts on your strength of the 2034 and 2040 patents I know they're only challenge 2040, but what are next steps here? And how does the company think about that? And then I'll have a more great quick follow-up.

然後第二個是——我們確實看到了 Auvelity 的（聽不清）保密協議。如果您能就您在 2034 年和 2040 年專利方面的優勢向我們提供總體想法，我知道它們只是挑戰 2040 年，但接下來的步驟是什麼？公司對此有何看法？然後我會進行更快速的跟進。

Yes. Thanks for the question on the cutoff date. That would be as of the last reporting week, which is February 17.

是的。感謝您提出有關截止日期的問題。那將是截至最後一個報告週，即 2 月 17 日。

And you cut-off, from the second part of the question.

你從問題的第二部分中斷了。

Yes. So just in terms of -- we saw the NDA submission from challenging those 2040 patents. So what are sort of the next steps in terms of litigation or in terms of potential settlement? And maybe if you could just comment on your confidence in the strength of the 2040 and the 2034 patents for Auvelity?

是的。因此，就-我們看到了挑戰那些 2040 年專利的 NDA 提交。那麼，就訴訟或潛在和解而言，接下來的步驟是什麼？也許您可以評論一下您對 Auvelity 2040 和 2034 專利實力的信心？

Okay. So Hunter will take that.

好的。所以亨特會接受的。

I am Hunter Murdock, Company's General Counsel. So as we've previously announced earlier this month, we did receive the Paragraph IV Notice from Teva relating to Auvelity. The receipt of the letter was normal, was an expected part of the process. And to get to your question, it's no way indicative of the quality of our IP portfolio, which we're extremely proud of.

我是 Hunter Murdock，公司的總法律顧問。因此，正如我們本月早些時候宣布的那樣，我們確實收到了 Teva 關於 Auvelity 的第 IV 段通知。收到信件是正常的，是流程的預期部分。回答你的問題，這並不能說明我們引以為豪的知識產權組合的質量。

Under the (inaudible) Act, we have 45 days of final wall street against Teva, if we wish to invoke the 30-month regulatory stay, and we're carefully analyzing Paragraph IV Notice right now. We're carefully evaluating our next step. (inaudible) able to provide much additional commentary regarding the notice or the steps you may be delighted data for future legal proceedings.

根據（聽不清）法案，如果我們希望援引 30 個月的監管中止期，我們有 45 天的最後華爾街反對 Teva，我們現在正在仔細分析第 IV 段通知。我們正在仔細評估我們的下一步。 （聽不清）能夠提供更多關於通知或步驟的更多評論，您可能會為未來的法律訴訟提供數據。

Great. And then just really quickly, I know you mentioned that for narcolepsy, the Phase II and the Phase III would be sufficient on an efficacy standpoint. Would you need an additional open-label safety experience? And will you have that necessary exposure once this trial reads out?

偉大的。然後很快，我知道你提到過對於發作性睡病，從療效的角度來看，II 期和 III 期就足夠了。您是否需要額外的開放標籤安全體驗？一旦這個試驗結束，你會得到必要的曝光嗎？

We do have the label safety extension trial in on. So that will be -- that safety experience will be part of the filing. As a reminder, in conjunction with our licensing deal with Pfizer did get the safety data, which is the same experience, which is extensive with the molecule, that will also be part, but I shouldn't get success.

我們確實進行了標籤安全擴展試驗。因此，安全經驗將成為備案的一部分。提醒一下，結合我們與輝瑞公司的許可協議，確實獲得了安全數據，這是相同的經驗，對分子有廣泛的經驗，這也將是一部分，但我不應該取得成功。

Our next question is from the line of David Hoang with SBMC.

我們的下一個問題來自 SBMC 的 David Hoang。

So I just had a quick question on gross to net for Auvelity in coming quarters. Can you give us any sense of how quickly we should expect the to improve over time? And would improvement correlate with the rate at which you can establish favorable coverage at major health insurance plans? I know you mentioned 6 to 9-month window for that to generally take place. Is that fair to assume GTN should also improve over that time?

所以我只是有一個關於 Auvelity 在未來幾個季度的毛淨值的快速問題。你能告訴我們隨著時間的推移我們應該期望多快的改進嗎？改善是否與您可以在主要健康保險計劃中建立有利覆蓋面的速度相關？我知道你提到了 6 到 9 個月的時間窗口，通常會發生這種情況。假設 GTN 也應該隨著時間的推移而改善是否公平？

Yes, David, thanks, it's Nick. I think that's the guidance that we previously gave and we're really staying to that.

是的，大衛，謝謝，我是尼克。我認為這是我們之前給出的指導，我們真的會堅持下去。

It's hard to give any further quantitative guidance on GTN until we start seeing broad payer coverage and then we'll be able to give a good sense of what the GTN and where the GTN will lie. So several quarters from now, I think we'll be able to give a better -- give you a better sense of where GTNs will be.

在我們開始看到廣泛的付款人覆蓋範圍之前，很難對 GTN 提供任何進一步的量化指導，然後我們將能夠很好地了解 GTN 是什麼以及 GTN 將位於何處。所以從現在開始的幾個季度，我認為我們將能夠提供更好的 - 讓您更好地了解 GTN 的位置。

The next question is from the line of Yatin Suneja with Guggenheim Securities.

下一個問題來自古根海姆證券公司的 Yatin Suneja。

This is Eddie on for Yatin. Just a few from us. On AXS-12, can you just provide a little bit more detail on the timing of those data this year? And what you would need to see to give you confidence moving forward, especially with comparison to Sunosi? And then just a quick follow-up on the Auvelity inventory. How much of that 5.2 in reported revenue for the quarter was due to channel stocking?

這是亞丁的艾迪。就我們幾個。關於 AXS-12，您能否提供更多有關今年這些數據時間的詳細信息？你需要看到什麼才能讓你有信心前進，尤其是與 Sunosi 相比？然後只是對 Auvelity 庫存的快速跟進。本季度報告收入的 5.2 中有多少是由於渠道庫存？

You want to take the last question?

你想回答最後一個問題嗎？

Yes. I haven't quantified the actual amount related to specifically the inventory. But as I mentioned earlier on the question, roughly 2.5 weeks of future demand. So you can kind of ballpark with that is that 2.5 weeks, we do take GTN deductions on that. So even though it hasn't been sold, it's been sold to our distributor have sold channel. So we are accruing based on the proceeds or what we expect January's GTN would we follow on that.

是的。我還沒有量化具體與庫存相關的實際金額。但正如我之前在這個問題上提到的，大約 2.5 週的未來需求。因此，您可以大致估計 2.5 週，我們確實會扣除 GTN。所以雖然還沒有賣掉，但是已經賣給了我們的經銷商有售賣渠道。因此，我們根據收益或我們對 1 月份 GTN 的預期進行累積。

And with regards to the timing for AXS-12, we expect to have results from that trial in the first half of this year. So that's the guidance. And I think you can figure out what the first half is, so that would lead through the end of June.

關於 AXS-12 的時間安排，我們預計將在今年上半年獲得該試驗的結果。這就是指導。而且我認為您可以弄清楚上半年是什麼，這樣可以一直持續到 6 月底。

Then in terms of what we would want to see, we want to see a positive trial. And this is a placebo-controlled study. So I want to see a positive trial that would give us 2 studies that demonstrate efficacy of the product.

然後就我們希望看到的內容而言，我們希望看到積極的試驗。這是一項安慰劑對照研究。因此，我希望看到一項積極的試驗，這將為我們提供 2 項證明該產品功效的研究。

And with regards to the comparison to Sunosi, the indications are different. So Sunosi approved to treat because of lead times in patients with narcolepsy and AXS-12 studying or a few of cataplexy in patients with narcolepsy.

關於與 Sunosi 的比較，指示是不同的。因此 Sunosi 批准用於治療發作性睡病患者的提前期和 AXS-12 研究或發作性睡病患者的一些猝倒症。

And Eddie, if I could just add, Herriot, if you don't mind, just to help provide context there. For narcolepsy patients, 100% of all narcolepsy patients that were from excessive data sleepiness and it's only estimated that about 70% suffer from cataplexy, just going to give you context in terms of the patient.

Eddie，如果我可以補充一下，Herriot，如果你不介意的話，只是為了幫助提供背景信息。對於發作性睡病患者，100% 的發作性睡病患者都是由於數據過度嗜睡而導致的，據估計只有大約 70% 的患者患有猝倒症，我只是根據患者的情況為您提供背景信息。

Our next question comes from the line of Graig Suvannavejh with Mizuho Securities.

我們的下一個問題來自瑞穗證券的 Graig Suvannavejh。

Congrats on the quarter and the year. Maybe my question is a bit bigger picture in perspective as it relates to your marketed products and Auvelity and Sunosi, I know you've just launched Auvelity and you've just gotten your hands on Sunosi, but do you have a sense of at what point you as a company might be in a position to provide financial guidance around what you see for sales for each of those products and maybe even from a bigger picture perspective, could you remind us as you think about the total revenue opportunity for Auvelity or AXS-05 either in depression and also in AD agitation and what you -- how you think about Sunosi in EDS, both in OSA and narcolepsy?

祝賀季度和年度。也許我的問題是一個更大的視角，因為它涉及到你的營銷產品和 Auvelity 和 Sunosi，我知道你剛剛推出了 Auvelity 並且你剛剛接觸了 Sunosi，但是你有什麼感覺嗎？指出您作為一家公司可能能夠圍繞您所看到的每種產品的銷售情況提供財務指導，甚至可能從更大的角度來看，您能否在考慮 Auvelity 或 AXS 的總收入機會時提醒我們-05 無論是在抑鬱症還是在 AD 激動中，以及你 - 你如何看待 EDS 中的 Sunosi，無論是 OSA 還是發作性睡病？

I'm sorry, Graig, can you repeat the first part of your question 1 more time for me?

抱歉，Graig，你能再為我重複一遍問題的第一部分嗎？

Yes. It was really more a question around the timing of when as a company. You might feel that you're comfortable enough to buy financial guidance on forward-looking sales in any particular year for this? Is this a situation where perhaps maybe 3 years down the line or 2 years? Just how you're thinking about what might be comfortable?

是的。這實際上更像是一個關於公司時間的問題。您可能會覺得自己足夠放心，可以為此購買任何特定年份的前瞻性銷售財務指導？這種情況可能是 3 年還是 2 年？你怎麼想什麼可能會舒服？

Yes. I would say, obviously, the way you prefaced your question originally is we're in very early stages for Auvelity as well as Sunosi. So we haven't discussed when we would potentially give sales guidance as it relates to both products.

是的。我想說的是，很明顯，你最初提出問題的方式是我們處於 Auvelity 和 Sunosi 的早期階段。因此，我們沒有討論何時可能提供與這兩種產品相關的銷售指導。

One would though, with Sunosi being a somewhat more mature product that we would be able to give some guidance on that product first. Auvelity, we're looking at various models here and would fluctuate drastically. So we're -- it would be further along. I can't be as to the timing when we give sales guidance.

不過，由於 Sunosi 是一種更成熟的產品，我們可以首先就該產品提供一些指導。 Auvelity，我們在這裡查看各種模型，並且會大幅波動。所以我們 - 它會更進一步。我不能確定我們提供銷售指導的時間。

What we did -- second part of your question here, we have talked about the sales potential, the peak sales potentials or both Auvelity as well as Sunosi. Starting with the Sunosi, current indication, we expect the product -- we believe that the product that $300 million to $500 million. And we've also said that we believe the product has brought us a potential leading sales potential of at least $1 billion, if you take into account the potential new indications.

我們所做的——你的問題的第二部分，我們已經討論了銷售潛力、銷售潛力峰值或 Auvelity 和 Sunosi。從目前的跡象 Sunosi 開始，我們預計該產品——我們相信該產品價值 3 億至 5 億美元。我們還說過，如果考慮到潛在的新適應症，我們相信該產品為我們帶來了至少 10 億美元的潛在領先銷售潛力。

And as we discussed, we are about to launch the pivotal trial And with regards to Auvelity, we think that Auvelity has $1 billion potential in both individual as well as in Alzheimer's disease agitation individually.

正如我們所討論的，我們即將啟動關鍵試驗關於 Auvelity，我們認為 Auvelity 在個人和阿爾茨海默病激越方面都有 10 億美元的潛力。

Based upon the size of that market in terms of the number of patients who have in the treated, Alzheimer's disease based upon not just the prevalence of Alzheimer's disease and the percentage of patients who have agitation, which is about 70%, also make on the fact that there's nothing grid currently to treat those patients.

根據接受治療的患者數量方面的市場規模，阿爾茨海默氏病不僅基於阿爾茨海默氏病的患病率和患有躁動症的患者百分比（約 70%），也使事實上，目前沒有任何網格可以治療這些患者。

And then maybe one more follow-up for me. Just on Sunosi, where the split in its current use is, I believe, 70% in OSA and 30% currently in narcolepsy, I'm wondering if as you look out in the future with your current plans, whether that is a number that will evolve from there or if it will stay there. And if it does evolve, any sense on which direction it might evolve in terms of that split?

然後也許對我來說還有一個後續行動。就 Sunosi 而言，我相信其目前使用的分歧是 70% 用於 OSA，30% 目前用於發作性睡病，我想知道當你根據當前計劃展望未來時，這個數字是否將從那裡發展，或者它是否會留在那裡。如果它真的進化了，那麼從分裂的角度來看，它可能會朝哪個方向進化？

Yes. Thanks, Graig. I don't think -- or I don't foresee especially in this current indication, but that's gone to evolve much as I mentioned before, our focus is heavily on OSA, just given the sheer size of the prevalence of that position, but we're not taking our foot off the gas on a narcolepsy also it is a very, very efficacious product in from narcolepsy.

是的。謝謝，格雷格。我不認為 - 或者我沒有特別預見到當前的跡象，但正如我之前提到的那樣，這已經發生了很大變化，我們的重點主要放在 OSA 上，只是考慮到該職位的普遍規模，但我們並沒有在發作性睡病上鬆懈，它也是一種非常非常有效的發作性睡病產品。

Next question comes from the line of Bert Hazlett with BTIG.

下一個問題來自 BTIG 的 Bert Hazlett。

My question is on the smoking cessation program. Could you just frame some of the parameters and timing surrounding the Phase II/III there, size of trial, again, timing, endpoints, things like that? And then with regard to the administration dosing of AXS-05, would you expect it's it to be dosed in similar fashion titration to a top dose as it is in MDD and AD agitation?

我的問題是關於戒菸計劃。你能不能就 II/III 期周圍的一些參數和時間安排、試驗規模、時間安排、終點等進行框架設計？然後關於 AXS-05 的給藥劑量，您是否期望它以與 MDD 和 AD 激動類似的方式滴定到最高劑量？

Thanks, Bert, for the question. With regards to the timing. We do expect to initiate the Phase II/III trial in the fourth quarter of this year. The team is working very hard to get that done. And sort of the design of the trial, this will be a standard trial design. We will have more to say once we launch the trial as well always do, we'll provide details in terms of the endpoints that we're looking at.

謝謝，伯特，提出這個問題。關於時機。我們確實希望在今年第四季度啟動 II/III 期試驗。團隊正在非常努力地完成這項工作。以及試驗的設計，這將是一個標準的試驗設計。一旦我們像往常一樣啟動試驗，我們將有更多話要說，我們將提供我們正在查看的端點方面的詳細信息。

But rest assured that the endpoints will be registration endpoints. And we have gotten feedback from the FDA on exactly what that will look like, and will provide bit detail to those trials. And in terms of the dose recommended we'll also provide that information once we launch the study.

但請放心，端點將是註冊端點。我們已經從 FDA 那裡得到了關於這將是什麼樣子的反饋，並將為這些試驗提供一些細節。就推薦劑量而言，一旦我們啟動研究，我們也會提供該信息。

At this time, we have time for to take 2 more additional questions. The next question comes from Myles Minter with William Blair.

此時，我們有時間再回答 2 個附加問題。下一個問題來自 Myles Minter 和 William Blair。

Just wondering how many or what percentage of (inaudible) are actually represented through the plans that will use that GPO you bought online last month and when you anticipate those plans making those decisions?

只是想知道將使用您上個月在線購買的 GPO 的計劃實際上代表了多少（聽不清），以及您預計這些計劃何時做出這些決定？

Yes. Mike, I'll take that one. So as updated in the prepared remarks, it was 1 of the 3 GPOs that are currently operating right now. Each of the 3 have a fairly substantial amount of covered lives and the PBMs and plans that are underneath them now have the ability to access those contractor rates.

是的。邁克，我要那個。因此，正如在準備好的評論中更新的那樣，它是目前正在運營的 3 個 GPO 中的一個。這 3 個中的每一個都有相當數量的承保人壽，並且它們下面的 PBM 和計劃現在能夠訪問這些承包商費率。

Once they work through their standard and expect 6 to 9 months (inaudible). So discussions are active with other -- the other GPOs and payers, both from clinical reviews as well as discussions on formulary decisions. We do expect that to be made over the next 6 months.

一旦他們完成了他們的標準，預計需要 6 到 9 個月（聽不清）。因此，與其他 - 其他 GPO 和付款人的討論很活躍，既有臨床審查，也有關於處方決定的討論。我們確實希望在接下來的 6 個月內完成。

Okay. And then just as a follow-up. Last year, when you met with the FDA and you decided to run advance to I think did they guide that they wanted to see an additional placebo-controlled study for AD agitation because they wanted to see additional placebo-controlled efficacy as well as safety data at that time and that time or commentary changed at the current meeting that you just had?

好的。然後作為後續行動。去年，當你與 FDA 會面並決定提前進行時，我認為他們是否指導他們希望看到額外的安慰劑對照研究來治療 AD 激越，因為他們希望看到額外的安慰劑對照療效和安全性數據在你剛剛舉行的當前會議上，當時和當時或評論發生了變化？

Sure. Thanks, Myles, for the question. When we made the decision to initiate the ADVANCE-2 trial, that was a decision that we made just from a business perspective. And so that is not based upon requirement or feedback from the FDA. However, once we didn't meet with safety data, in particular, placebo-controlled safety data as well as safety database based on ICH guidelines that less information that was provided to that will be a requirement for the filing.

當然。謝謝邁爾斯提出這個問題。當我們決定啟動 ADVANCE-2 試驗時，這是我們從商業角度做出的決定。因此，這不是基於 FDA 的要求或反饋。然而，一旦我們沒有遇到安全數據，特別是安慰劑對照的安全數據以及基於 ICH 指南的安全數據庫，那麼提供的信息就會較少，這將是備案的要求。

Our final question is from the line of Matt Kaplan with Ladenburg Thalmann.

我們的最後一個問題來自 Matt Kaplan 和 Ladenburg Thalmann。

This is in for Matt. Congrats on the quarter. Just a quick one. I wanted to ask about Auvelity platform. You've had early success with I was wondering how DCC and your initial experience with Auvelity kind of driven sales? And any initial learnings that you'd hope to incorporate as the large progresses?

這是給馬特的。祝賀這個季度。只是一個快速的。我想問一下 Auvelity 平台。你已經取得了早期的成功，我想知道 DCC 和你對 Auvelity 的初步經驗是如何推動銷售的？隨著大的進步，您希望納入任何初步的學習嗎？

Yes, thanks for the questions, good one. So as you mention, we have talked about what we're seeing on Sunosi, so I won't rehash that. And on Auvelity, we're still very early. What we've done is we've established a platform, the same platform that Sunosi is operating off of.

是的，謝謝你的提問，很好。所以正如你提到的，我們已經討論了我們在 Sunosi 上看到的東西，所以我不會重複。在 Auvelity 上，我們還很早。我們所做的是建立了一個平台，與 Sunosi 運營的平台相同。

We are very confident in our sales force size as well as the tools that we've given them to reach the number of HCPs up that we believe will drive rapid growth. And so it's a bit too early to really comment on that. But we are very pleased with how the team is using the platform and how they are helping drive growth that way.

我們對我們的銷售隊伍規模以及我們提供給他們的工具非常有信心，以達到我們認為將推動快速增長的 HCP 數量。因此，現在就此發表評論還為時過早。但我們對團隊如何使用該平台以及他們如何以這種方式幫助推動增長感到非常滿意。

I will now turn the call back to Axsome's CEO for any concluding remarks.

我現在將把電話轉回給 Axsome 的首席執行官，聽取任何結束語。

Well, thank you again for joining us on the call today. We are proud of the hard work of the Axsome team which is now resulting in meaningful differences in patients' lives. This is only the start of more great things to come.

好吧，再次感謝您今天加入我們的電話會議。我們為 Axsome 團隊的辛勤工作感到自豪，他們現在正在為患者的生活帶來有意義的改變。這只是未來更偉大事物的開始。

2022 was a pivotal year for Axsome. We are not the same company we were a year ago, and were wanting the same company next year with all the strategic growth we anticipate. We are aligned to report value-driving updates with multiple and state track candidates in multiple stage clinical trials in some of the most challenging to treat CNS disorders in the next 12 to 18 months. Axsome has 5 commercial products in the market by 2025, and we're hard at work to meet those goals. Thank you. Have a great rest of your day.

2022 年對 Axsome 來說是關鍵的一年。我們與一年前的公司不同，我們希望明年成為同一家公司，實現我們預期的所有戰略增長。在未來 12 至 18 個月內，我們將在一些最具挑戰性的中樞神經系統疾病治療中，與多階段臨床試驗中的多個和狀態跟踪候選人一起報告價值驅動更新。到 2025 年，Axsome 將有 5 種商業產品投放市場，我們正在努力實現這些目標。謝謝。祝您度過愉快的一天。

This will conclude today's conference. Thank you for your participation. You may now disconnect your lines at this time.

今天的會議到此結束。感謝您的參與。此時您可以斷開線路。