SAGE Therapeutics Inc (SAGE) 2024 Q4 法說會逐字稿

Good afternoon. Welcome to Sage Therapeutics' fourth-quarter and full-year 2024 financial results conference call. (Operator Instructions) This call is being webcast live on the Investors and Media section of Sage's website at sagerx.com. This call is the property of Sage Therapeutics, and recording, reproduction, or transmission of this call without the express written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded.

午安.歡迎參加 Sage Therapeutics 2024 年第四季和全年財務業績電話會議。（操作員指示）本次電話會議將在 Sage 網站 sagerx.com 的投資者和媒體部分進行網路直播。本次通話由 Sage Therapeutics 所有，未經 Sage Therapeutics 明確書面同意，嚴禁錄製、複製或傳輸本次通話。請注意，本次通話正在錄音。

I would now like to introduce Ashley Kaplowitz, Vice President of Investor Relations and Capital Markets at Sage.

現在，我想介紹 Sage 投資者關係和資本市場副總裁 Ashley Kaplowitz。

Good afternoon, and thank you for joining Sage Therapeutics' fourth-quarter and full-year 2024 financial results conference call. Before we begin, I encourage everyone to go to the Investors And media section of our website at sagerx.com, where you can find the press release and slides related to today's call.

下午好，感謝您參加 Sage Therapeutics 2024 年第四季和全年財務業績電話會議。在我們開始之前，我鼓勵大家造訪我們網站 sagerx.com 的投資者和媒體部分，您可以在那裡找到與今天的電話會議相關的新聞稿和幻燈片。

I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. Please review the risk factors discussed in today's press release and in our SEC filings for additional details.

我想指出的是，我們將做出前瞻性的陳述，這些陳述是基於我們目前的預期和信念。這些聲明受一定風險和不確定性的影響，我們的實際結果可能有重大差異。請查看今天的新聞稿和我們的美國證券交易委員會文件中討論的風險因素以獲取更多詳細資訊。

We will begin the call with prepared remarks by Barry Greene, our Chief Executive Officer, who will provide an overview of our progress during the fourth quarter and full year 2024. Our Chief Operating Officer, Chris Benecchi, will provide an update on the ongoing commercialization of ZURZUVAE and key financial results. Our Chief Medical Officer, Laura Gault, will then provide a brief update on our pipeline. In addition, Mike Quirk, our Chief Scientific Officer, will be available for questions during the Q&A portion of the call.

我們的執行長 Barry Greene 將以準備好的發言開始電話會議，他將概述我們在 2024 年第四季和全年的進展。我們的營運長 Chris Benecchi 將提供有關 ZURZUVAE 正在進行的商業化進展和關鍵財務結果的最新情況。我們的首席醫療官 Laura Gault 隨後將簡要介紹我們的產品線。此外，我們的首席科學官 Mike Quirk 將在電話會議的問答環節回答問題。

With that, I'll now turn the call to Barry.

說完這些，我現在將電話轉給巴里。

Thanks, Ashley, and thank you, everyone, for joining us this afternoon. 2024 was an important year for Sage, underscored by the early commercial success of ZURZUVAE, the first and only oral treatment approved for adults with postpartum depression or PPD. We enter 2025 with a plan to build on ZURZUVAE's commercial momentum, a recalibrated R&D approach, and a commitment to financial discipline as we focus on enhancing growth for our shareholders.

謝謝，阿什利，也謝謝大家今天下午加入我們。 2024 年對 Sage 來說是重要的一年，尤其重要的是 ZURZUVAE 的早期商業成功，ZURZUVAE 是第一個也是唯一一個獲準用於治療產後憂鬱症或 PPD 成人患者的口服治療藥物。我們邁入 2025 年，計劃借助 ZURZUVAE 的商業發展動能、重新調整的研發方法和對財務紀律的承諾，專注於為股東實現成長。

As we outlined at the JPMorgan conference in January, we're focused on executing against the three core priorities in 2025, which are intended to deliver short-, medium-, and long-term value creation for shareholders and serve unmet needs of patients and families. Our foremost priority is to continue efforts to establish ZURZUVAE as a standard of care for PPD.

正如我們在一月份的摩根大通會議上所概述的那樣，我們專注於實現 2025 年的三大核心重點任務，旨在為股東創造短期、中期和長期價值，並滿足患者和家庭尚未滿足的需求。我們的首要任務是繼續努力將 ZURZUVAE 確立為 PPD 的護理標準。

The first year of launch exceeded expectations, and we plan to invest in 2025 to fuel top-line revenue growth. In 2024, we were pleased to see more than 6,600 shipments of ZURZUVAE to women with PPD, which we believe reflects the growing demand for a fast-acting treatment for PPD and physician adoption across HCPs who treat PPD.

推出的第一年就超出了預期，我們計劃在 2025 年進行投資以推動營收成長。2024 年，我們很高興看到向患有 PPD 的女性運送了超過 6,600 份 ZURZUVAE，我們認為這反映了對快速治療 PPD 的需求日益增長，以及治療 PPD 的 HCP 中的醫生的採用。

There are two important dynamics we're starting to see as the launch progresses: a promotionally responsive market and a system-wide paradigm shift. Specifically, we're seeing signs of ZURZUVAE changing practice patterns among OB-GYNs and elevating a national dialogue around maternal mental health. These dynamics have the potential to accelerate growth and further drive urgency among HCPs in treating PPD.

隨著發布的進展，我們開始看到兩個重要的動態：促銷響應市場和系統範圍的範式轉移。具體來說，我們看到 ZURZUVAE 正在改變婦產科醫生的實踐模式並提升圍繞產婦心理健康的全國對話的跡象。這些動態有可能加速成長並進一步推動 HCP 治療 PPD 的迫切性。

We believe these early successes validate our commercial strategy and provide greater evidence that ZURZUVAE is the key to unlocking blockbuster potential in PPD. Importantly, that means helping many women suffering from this urgent medical condition.

我們相信這些早期的成功驗證了我們的商業策略，並提供了更大的證據證明 ZURZUVAE 是釋放 PPD 重磅藥物潛力的關鍵。重要的是，這意味著幫助許多患有這種緊急疾病的女性。

In addition to building on the commercial momentum of ZURZUVAE, we're prioritizing our pipeline to focus on neuropsych and neurodevelopmental disorders. We believe a recalibrated R&D approach can create value over the long term. Laura will provide additional details on SAGE-319 and SAGE-324, as well as our NMDA receptor NAM platform.

除了鞏固 ZURZUVAE 的商業動能之外，我們還優先考慮神經心理和神經發育障礙。我們相信重新調整的研發方法可以創造長期價值。勞拉將提供有關 SAGE-319 和 SAGE-324 以及我們的 NMDA 受體 NAM 平台的更多詳細資訊。

Lastly, we're committed to maintaining the strength of our financial position. With the commercial momentum of ZURZUVAE PPD, our R&D approach, and expected cash runway to mid-2027, we believe we are well positioned to focus on our goal of creating value for our shareholders.

最後，我們致力於維持強勁的財務狀況。憑藉 ZURZUVAE PPD 的商業發展勢頭、我們的研發方法以及預計到 2027 年中期的現金流，我們相信我們已準備好專注於為股東創造價值的目標。

Now before I turn the call over to Chris, I want to briefly acknowledge Biogen's unsolicited non-binding proposal to acquire Sage, as well as our Board's decision to initiate a strategic alternative process. As we stated in our press release last month, the Sage Board concluded that the proposal significantly undervalues Sage and is not in the best interests of shareholders. The Board also decided to initiate a strategic review to evaluate a broad range of opportunities to maximize value for shareholders.

現在，在我將電話轉給克里斯之前，我想簡要地介紹一下 Biogen 收購 Sage 的未經請求的非約束性提議，以及我們董事會啟動戰略替代流程的決定。正如我們上個月在新聞稿中所述，Sage 董事會認為該提案嚴重低估了 Sage 的價值，不符合股東的最佳利益。董事會也決定啟動策略審查，以評估各種機會，從而實現股東價值最大化。

As a reminder, we've not set a timetable for the review process, nor is there any assurance that the review process will result in any transaction or other strategic outcome. With this in mind, we will not be talking about this further on this call. I do appreciate your understanding.

提醒一下，我們沒有為審查過程設定時間表，也不保證審查過程會產生任何交易或其他策略結果。考慮到這一點，我們將不會在本次電話會議中進一步討論此問題。我非常感謝您的體諒。

And with that, we'll move forward, and I'll now turn the call over to Chris. Chris?

這樣，我們就可以繼續前進了，現在我將電話交給克里斯。克里斯？

Thanks, Barry. As mentioned, we've made tremendous progress in the first full year of ZURZUVAE's launch in PPD, and I'm excited to discuss our recent achievements and ongoing initiatives. Afterwards, I'll review our results for the fourth quarter and full year 2024.

謝謝，巴里。如上所述，ZURZUVAE 在 PPD 領域推出的第一年，我們取得了巨大進展，我很高興討論我們最近的成就和正在進行的舉措。之後，我將回顧我們 2024 年第四季和全年的業績。

Starting with the launch of ZURZUVAE, we are pleased to see consistent demand growth quarter over quarter with nearly 2,500 prescriptions shipped to women with PPD in Q4. This represents a 21% increase from the third quarter of 2024, even with far fewer days in the field engaging with customers due to the holiday season.

從 ZURZUVAE 的推出開始，我們很高興看到需求逐季持續增長，第四季度向患有 PPD 的女性發送了近 2,500 份處方。儘管由於假期原因，在現場與客戶互動的日子大大減少，但這比 2024 年第三季仍增長了 21%。

Across the full year of 2024, more than 6,600 prescriptions of ZURZUVAE were shipped to women with PPD. We believe that we have continued to see strong demand growth in patient shipments because HCPs are becoming confident in the value proposition of ZURZUVAE and what it potentially delivers.

2024 年全年，有超過 6,600 張 ZURZUVAE 處方被寄給患有 PPD 的女性。我們相信，我們將繼續看到患者出貨量的強勁需求成長，因為 HCP 對 ZURZUVAE 的價值主張及其潛在價值越來越有信心。

In the fourth quarter, ZURZUVAE was prescribed across a breadth of HCPs who treat PPD, including OB-GYNs, psychiatrists, and PCPs. Almost 80% of those prescriptions came from OB-GYNs, who are the foundational focus of our launch strategy since they see women throughout their peripartum journey, the most critical time to screen, diagnose, and treat.

在第四季度，ZURZUVAE 被廣泛用於治療 PPD 的 HCP，包括婦產科醫生、精神科醫生和 PCP。其中近 80% 的處方來自婦產科醫生，她們是我們發布策略的基礎焦點，因為她們會在女性的整個圍產期（即篩檢、診斷和治療的最關鍵時期）看診。

While OB-GYNs are at the forefront, we believe that over time we will continue to see utilization of ZURZUVAE increase among all HCPs who treat women with this condition. More than 70% of ZURZUVAE patients are receiving ZURZUVAE as their first new treatment for PPD.

雖然婦產科醫生處於最前沿，但我們相信，隨著時間的推移，我們將繼續看到所有治療患有這種疾病的女性的醫療保健人員對 ZURZUVAE 的使用率增加。超過 70% 的 ZURZUVAE 患者接受 ZURZUVAE 作為第一個 PPD 新療法。

Further, we saw strong trends among prescribers in 2024, with about 60% of targeted HCPs writing repeat prescriptions after prescribing ZURZUVAE. We also see that once an OB-GYN has prescribed ZURZUVAE, there is a significant increase in the number of women with PPD they treat based on prescriptions for all medications.

此外，我們發現 2024 年處方人員呈現強勁趨勢，約 60% 的目標 HCP 在開出 ZURZUVAE 後會開立重複處方。我們還發現，一旦婦產科醫生開出 ZURZUVAE，根據所有藥物的處方，接受治療的產後憂鬱症女性數量將顯著增加。

Our messages are resonating. ZURZUVAE has a greater than 90% aided brand awareness among OB-GYNs and psychiatrists. Before I turn to our plans for 2025, I'll provide an update on coverage.

我們的訊息引起了共鳴。ZURZUVAE 在婦產科醫生和精神科醫生中的輔助品牌知名度超過 90%。在介紹我們的 2025 年計畫之前，我將提供最新報道。

As of today, greater than 95% of commercial and Medicaid lives are covered or have a path to coverage, with the majority having no step edits or complex prior authorizations. This remarkable level of coverage one year into launch reflects payer recognition of the value proposition of ZURZUVAE, which enables broad and equitable access for all women with PPD.

截至今天，超過 95% 的商業和醫療補助計劃受益人都已獲得保障或有獲得保障的途徑，其中大多數人無需進行分步編輯或複雜的事先授權。推出一年後如此顯著的覆蓋水準反映了付款人對 ZURZUVAE 價值主張的認可，該方案使所有患有 PPD 的女性都能獲得廣泛和公平的治療機會。

To support the continued scaling of ZURZUVAE, we plan to move forward with a robust investment plan which includes a joint sales force expansion to cover a wider reach of healthcare providers, investment in media opportunities intended to further amplify the message that PPD is an urgent medical condition, and greater visibility via social media designed to increase awareness and educational efforts. We are also planning to expand ZURZUVAE DTC, including the potential for targeted branded TV media later this year. Today's technology allows us to meet women with PPD in their most trusted channels, empowering them to speak to their physician about their PPD symptoms and appropriate treatment options.

為了支持 ZURZUVAE 的持續擴大，我們打算推進一項強有力的投資計劃，其中包括擴大聯合銷售隊伍以涵蓋更廣泛的醫療保健提供者、投資媒體機會以進一步擴大 PPD 是一種緊急醫療狀況的信息，以及透過社交媒體提高知名度以提高認識和教育力度。我們還計劃擴大 ZURZUVAE DTC，包括今年稍後推出針對性的品牌電視媒體。現今的科技使我們能夠透過她們最信任的管道與患有產後憂鬱症的女性見面，使她們能夠與醫生討論她們的產後憂鬱症症狀和適當的治療方案。

In terms of personal promotion, we are already seeing an early impact from the sales force expansion. In the territories where we expanded our sales force in the fourth quarter, we saw a 33% growth rate in patient shipments. We believe these efforts are important as we are seeing PPD to be a promotionally responsive market with significant growth potential.

在個人晉升方面，我們已經看到銷售隊伍擴張帶來的早期影響。在我們第四季擴大銷售團隊的地區，病患出貨量成長率達到 33%。我們認為這些努力非常重要，因為我們看到 PPD 是一個具有巨大成長潛力的促銷響應市場。

We have made remarkable progress in 2024 and are continuing to think big about the commercialization of ZURZUVAE as a treatment for women with PPD. We look forward to sharing additional updates in the coming quarters.

我們在 2024 年取得了顯著進展，並繼續積極考慮將 ZURZUVAE 商業化，用於治療女性 PPD。我們期待在接下來的幾個季度分享更多更新。

Now turning to our financial results for the fourth quarter and full year of 2024. As a reminder, our full financial results for these periods are detailed in our press release issued this afternoon.

現在來談談我們 2024 年第四季和全年的財務表現。提醒一下，我們這些時期的完整財務業績已詳細說明在我們今天下午發布的新聞稿中。

We reported collaboration revenue from the sales of ZURZUVAE of $11.4 million in the fourth quarter, a 4% increase compared to the third quarter of 2024 and $36.1 million for the full year. As a reminder, our reported collaboration revenue is 50% of the net revenues Biogen reports for ZURZUVAE.

我們報告稱，第四季度 ZURZUVAE 銷售的合作收入為 1,140 萬美元，較 2024 年第三季成長 4%，全年成長 3,610 萬美元。提醒一下，我們報告的合作收入是 Biogen 報告的 ZURZUVAE 淨收入的 50%。

It is important to note that while revenue may fluctuate based on inventory dynamics, we continue to see strong quarter over quarter demand growth in patient shipments and expect this growth to continue. R&D expenses were $37 million, and SG&A expenses were $54 million in the fourth quarter of 2024.

值得注意的是，雖然收入可能根據庫存動態而波動，但我們仍然看到患者出貨量逐季強勁需求成長，並預計這種成長將持續下去。2024 年第四季的研發費用為 3,700 萬美元，銷售、一般及行政費用為 5,400 萬美元。

Additionally, there were one-time restructuring expenses of $22.5 million in the fourth quarter of 2024. While ZURZUVAE joint commercialization investment will increase in 2025, we anticipate overall operating expenses will substantially decrease in 2025 relative to 2024. This reflects reductions in R&D and G&A from our pipeline prioritization and the cost savings from the October 2024 reorganization. The first full-quarter of savings are expected to be realized in Q1 of 2025. Our net loss for the fourth quarter of 2024 was $95.8 million.

此外，2024 年第四季還有 2,250 萬美元的一次性重組費用。雖然 ZURZUVAE 聯合商業化投資將在 2025 年增加，但我們預計 2025 年的整體營運費用將相對於 2024 年大幅下降。這反映了我們優先考慮產品線所帶來的研發和一般行政支出的減少，以及 2024 年 10 月重組所帶來的成本節省。預計第一個完整季度的節省將在 2025 年第一季實現。我們 2024 年第四季的淨虧損為 9,580 萬美元。

Based upon our current operating plan, we anticipate that our existing cash, cash equivalents, and marketable securities of $504 million as of December 31, 2024, together with the anticipated funding from ongoing collaborations and estimated revenues and excluding any potential milestone payments we may receive under our collaboration agreements will support our operations to mid-2027.

根據我們目前的營運計劃，我們預計，截至 2024 年 12 月 31 日，我們現有的現金、現金等價物和有價證券為 5.04 億美元，加上預期來自持續合作和預計收入的資金（不包括我們根據合作協議可能收到的任何潛在里程碑付款），將支持我們運營到 2027 年中期。

Now with that, I'll turn the call over to Laura. Laura?

現在，我將把電話轉給勞拉。勞拉？

Thanks, Chris. As Barry mentioned earlier, we remain focused on developing medicines for neuropsychiatry and neurodevelopmental disorders, where there is a strong scientific rationale and opportunities to address meaningful unmet needs.

謝謝，克里斯。正如 Barry 之前提到的，我們仍然專注於開發針對神經精神病學和神經發育障礙的藥物，這具有強大的科學原理和機會來滿足有意義的未滿足需求。

I'll begin with SAGE-319. Our wholly owned, extrasynaptic-preferring, GABAA receptor, positive allosteric modulator or PAM, which is designed to have novel pharmacology and a differentiated profile from other GABAA PAMs in our portfolio. SAGE-319 is currently being investigated as a potential treatment for behavioral symptoms associated with certain neurodevelopmental disorders, including autism spectrum disorder, Tourette's syndrome, and other rare neurological disorders. These disorders place a high burden on patients, families, and the healthcare system.

我將從 SAGE-319 開始。我們全資擁有的、突觸外優先的 GABAA 受體、正變構調節劑或 PAM，旨在具有新穎的藥理學和與我們產品組合中的其他 GABAA PAM 不同的特性。SAGE-319 目前正在被研究作為治療某些神經發育障礙相關的行為症狀的潛在療法，包括自閉症譜系障礙、妥瑞氏症和其他罕見的神經系統疾病。這些疾病給患者、家庭和醫療保健系統帶來了沉重的負擔。

We are currently conducting a Phase 1 multiple ascending dose, or MAD, study to help us better understand the safety, tolerability, and target engagement of SAGE-319 across a range of doses. We expect to share data from the Phase 1 MAD study by late 2025 and anticipate that the upcoming results from this study could enable potential studies in the patient population in early 2026.

我們目前正在進行第 1 階段多次遞增劑量 (MAD) 研究，以幫助我們更好地了解 SAGE-319 在一系列劑量下的安全性、耐受性和靶向作用。我們預計將在 2025 年底前分享第 1 階段 MAD 研究的數據，並預計研究即將得出的結果可在 2026 年初對患者群體進行潛在研究。

Further, we have two orally administered NMDA receptor negative allosteric modulators, or NAMs, in pre-clinical development: SAGE-817 and SAGE-039. Our intention with these drug candidates is to provide a drug with similar or better efficacy than NMDA receptor blockers like ketamine but with a potentially improved safety and tolerability profile. In addition, we continue to explore potential partnerships and out-licensing opportunities for some clinical and pre-clinical stage compounds.

此外，我們還有兩種口服 NMDA 受體負變構調節劑（NAM）處於臨床前開發階段：SAGE-817 和 SAGE-039。我們對這些候選藥物的目的是提供一種具有與氯胺酮等 NMDA 受體阻斷劑相似或更好療效但具有潛在改善的安全性和耐受性的藥物。此外，我們將繼續探索一些臨床和臨床前階段化合物的潛在合作夥伴關係和對外授權機會。

Lastly, as we have previously noted, we are also exploring SAGE-324 for potential indications, including seizures and developmental and epileptic encephalopathies or DEEs. We expect to provide an update on next steps, if any, in mid-2025. To be clear, we are not spending to further develop SAGE-324 now, but rather we are evaluating SAGE-324 as part of an overall portfolio decision.

最後，正如我們之前提到的，我們也正在探索 SAGE-324 的潛在適應症，包括癲癇、發育性和癲癇性腦病變或 DEE。我們預計將在 2025 年中期提供有關後續步驟的更新（如果有）。需要明確的是，我們現在不會花錢進一步開發 SAGE-324，而是將 SAGE-324 作為整體投資組合決策的一部分進行評估。

With that, I will turn it over to Ashley to help facilitate the Q&A portion of today's conference call.

接下來，我將把主題交給 Ashley，讓他幫忙主持今天電話會議的問答部分。

Thanks Laura. As a reminder, we will not be answering questions related to our Board's decision to reject Bijan's unsolicited acquisition proposal or to initiate a review of strategic alternatives and ask that questions be focused on our Q4 and full-year 2024 results.

謝謝勞拉。提醒一下，我們不會回答與董事會拒絕 Bijan 的主動收購提議或啟動戰略替代方案審查的決定有關的問題，並要求問題集中在我們的 2024 年第四季度和全年業績上。

Please limit yourself to one question. If you have additional questions, feel free to return to the queue. Now, I'll turn the call over to the operator to handle Q&A. Operator?

請限制自己只問一個問題。如果您還有其他問題，請隨時返回佇列。現在，我將把電話轉給接線員來處理問答。操作員？

Thank you. (Operator Instructions)

謝謝。（操作員指令）

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Hi, guys. Thanks for taking the question. Barry, I wanted to ask about Biogen buy-in to the expansion of the marketing opportunity or the marketing effort. You mentioned that the sales force expansion is underway. It's in certain geographies.

嗨，大家好。感謝您回答這個問題。巴里，我想問 Biogen 對擴大行銷機會或行銷力度的支持。您提到銷售隊伍擴張正在進行中。它存在於某些地區。

Can you elaborate on that? Specifically, has Biogen matched the personnel expansion that Sage has implemented or sort of the number and depth of the programs that Sage has put into place?

能詳細說明一下嗎？具體來說，Biogen 是否能匹敵 Sage 所實施的人員擴張，或者 Sage 所實施的項目數量和深度？

Thanks for the question, Ritu. I appreciate it. So based upon the performance we saw in 2024 and as Chris mentioned on the call, the success we saw in our sales force expansion, we entered 2025 with an aligned integrated commercialization plan. That includes not just the increase of sales force to a new level but also appropriate investment behind all the other aspects of our commercialization effort, namely medical affairs, disease state awareness, DTC, including continued progress on the coverage side, which is outstanding, but we want to continue to make better. So we're highly aligned and excited for a very successful 2025 helping as many moms as we can this year.

謝謝你的提問，Ritu。我很感激。因此，基於我們在 2024 年看到的表現，以及克里斯在電話會議上提到的，我們在銷售隊伍擴張方面看到的成功，我們帶著一致的綜合商業化計劃進入了 2025 年。這不僅包括將銷售團隊提升到新的水平，還包括在我們商業化努力的所有其他方面進行適當的投資，即醫療事務、疾病狀況意識、DTC，包括在覆蓋範圍方面的持續進展，這是非常出色的，但我們希望繼續做得更好。因此，我們高度一致，並對 2025 年的成功感到興奮，今年我們將盡力幫助盡可能多的媽媽。

Could we get a little more color on what the expanded efforts are?

我們能否更詳細地了解擴大的努力是什麼？

Let me ask Chris if he could provide some color.

讓我問克里斯他是否可以提供一些資訊。

Yeah. So beyond the point about sales force expansion, social media and a social media influencer campaign through TikTok and Instagram as well as Facebook are an important part of the social media effort designed to reach not only those that are living with PPD but also HCPs who are treating many of these women with PPD. As Barry noted, connected TV and DTC is an important part of how we think about another way to reach those that are living with PPD that are out in the community, as well as peer-to-peer education, digital efforts more broadly.

是的。因此，除了擴大銷售團隊之外，社交媒體和透過 TikTok、Instagram 和 Facebook 開展的社交媒體影響力活動也是社交媒體努力的重要組成部分，旨在不僅接觸患有 PPD 的人，而且還接觸為許多患有 PPD 的女性提供治療的 HCP。正如巴里所說，連網電視和 DTC 是我們思考如何以另一種方式接觸社區中患有 PPD 的人群，以及進行點對點教育和更廣泛的數位化努力的重要組成部分。

And I would round that out by saying that we have seen an interesting dynamic that we talked about in our prepared remarks, where this is not only about the work that we do to make sure that physicians and women with PPD are aware of ZURZUVAE, disease state awareness also plays an important role here in the importance of screening and diagnosis and all of this. So again, that's a key component to our initiatives in 2025 as we think about reaching as many women with PPD as possible.

最後，我想說的是，我們看到了一個有趣的動態，我們在準備好的評論中談到了這一點，這不僅涉及我們為確保醫生和患有 PPD 的女性了解 ZURZUVAE 所做的工作，疾病狀態意識在篩檢和診斷的重要性等方面也發揮著重要作用。所以，這是我們 2025 年計畫的關鍵組成部分，因為我們想盡可能地幫助患有 PPD 的女性。

Salveen Richter, Goldman Sachs.

高盛的薩爾文·里希特（Salveen Richter）。

Hi, thank you for taking my question. This is Shrunatra on for Salveen. Could you please elaborate on the inventory dynamics for the quarter, noting the slight disconnect between the prescription growth and the sales growth? And also, could you speak to the proportion of free drugs being provided in 4Q?

你好，謝謝你回答我的問題。這是為 Salveen 表演的 Shrunatra。您能否詳細說明本季的庫存動態，並注意到處方成長和銷售成長之間略有脫節？另外，您能談談第四季免費提供藥品的比例嗎？

Yeah, Shrunatra. So we're, as I just talked about, really happy with what we're seeing across the board in terms of 2024 performance, and that is we're seeing an OB-GYN step-up to own the disease, ACOG guidelines being in line. We're seeing a promotional responsive market, and we're seeing accelerants in terms of system-wide change. Media continues to cover ZURZUVAE and PPD at extraordinary high level.

是的，Shrunatra。因此，正如我剛才所說，我們對 2024 年的全面表現感到非常滿意，那就是我們看到婦產科正在加強對這種疾病的控制，這與 ACOG 指南相符。我們看到了一個促銷響應市場，我們也看到了系統範圍變革的加速器。媒體繼續對 ZURZUVAE 和 PPD 進行高水準通報。

So all the dynamics that set up ZURZUVAE entering blockbuster potential are there. We also were happy that we saw over 20% growth in demand quarter on quarter, and I'll ask Chris to talk about sort of the inventory dynamic. But just to be clear, by demand, demand is when especially pharma after a script has entered ships that prescription to moms. That's the true measure of future revenue, because that's the leading indicator.

因此，所有為 ZURZUVAE 進入大片市場潛力奠定基礎的動力都已經存在。我們也很高興看到需求較上季成長超過 20%，我會請克里斯談談庫存動態。但要明確的是，需求是指藥廠在收到處方後，將處方寄給媽媽們的需求。這是未來收入的真正衡量標準，因為這是領先指標。

But Chris, you want to talk about kind of inventory demand in the supply chain?

但是克里斯，你想談談供應鏈中的庫存需求嗎？

Revenue is measured when product moves from our alliance partner into the channel at the wholesaler level. Now when it comes to inventory management, there's inventory that sits at the specialty pharmacies and inventory that sits at the wholesalers, and what we saw over the fourth quarter is that based on channel dynamics, inventory can fluctuate through both what we've seen at specialty pharmacies as well as wholesalers. So as Barry noted, when it comes to truly measuring performance, really looking at demand quarter over quarter is the most important metric that we can look at as we go forward.

當產品從我們的聯盟夥伴轉移到批發商層面的管道時，我們就能衡量收入。現在談到庫存管理，有位於專業藥局的庫存和位於批發商的庫存，我們在第四季度看到的情況是，基於通路動態，庫存可能會在專業藥局和批發商處都發生波動。因此，正如巴里所說，當真正衡量績效時，真正專注於季度環比需求是我們未來可以關注的最重要的指標。

Now with respect to the question about free drug, we said that broad and equitable access is paramount for this launch, and we've really worked to ensure that broad and equitable access. Free drug plays a role. Free drug helps those that are not insured or underinsured have access to ZURZUVAE, moms with PPD who need this. And what we saw over the course of the fourth quarter is a reduction in the percentage of free drugs from what we saw in Q3,.

現在關於免費藥品的問題，我們說，廣泛和公平地獲得藥物對於這次發布至關重要，我們確實努力確保廣泛和公平地獲得藥物。免費藥物發揮作用。免費藥物可以幫助那些沒有保險或保險不足的人以及需要這種藥物的患有產後憂鬱症的媽媽們獲得 ZURZUVAE。我們發現，第四季免費藥品的比例較第三季下降。

And we would anticipate that based on additional coverage that we would see with respect to commercial and Medicaid plans, that that percentage would decrease over time. Again, very encouraging when it comes back to ensuring that all women with BPD have access to this very important medication.

我們預計，基於商業和醫療補助計劃的額外覆蓋範圍，該比例將隨著時間的推移而下降。再次，當我們確保所有患有 BPD 的女性都能獲得這種非常重要的藥物時，這非常令人鼓舞。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

Hey, guys. Thanks so much for taking the question. Just thinking a little bit more acutely about the first quarter, given historical sort of quarterly seasonality in one Q in the industry due to payer dynamics, how are you thinking about this relative to how we should be thinking about ZURZUVAE potential headwinds in the first quarter? Thanks so much.

嘿，大家好。非常感謝您回答這個問題。稍微仔細思考一下第一季度的情況，考慮到由於付款人的動態，該行業在一個季度中會出現歷史性的季度季節性，您如何看待這個問題，相對於我們應該如何看待第一季度的潛在阻力？非常感謝。

Yeah. Anupam, thanks for the question. I'll start and see if Chris wants to add color. So we anticipate a continued quarter-on-quarter growth, including the first quarter. And keep in mind that our reimbursement is commercial and Medicaid reimbursement. So we don't see a classic kind of Medicare donor hole first-quarter issue. We should see continued growth on all dimensions in the first quarter.

是的。Anupam，謝謝你的提問。我會開始看看克里斯是否想添加顏色。因此，我們預計包括第一季在內的季度環比將繼續增長。請記住，我們的報銷是商業和醫療補助報銷。因此，我們在第一季沒有看到典型的醫療保險捐贈缺口問題。我們應該會看到第一季各個方面都繼續成長。

Chris, anything to add?

克里斯，還有什麼要補充嗎？

What I would add is that we know this is a promotionally responsive market from what we saw over the course of the first full year. And what we saw when we increased the sales force during the fourth quarter of 2024, there were fewer selling days during the month of December, and it's part of November as well due to the holiday season. We don't anticipate that kind of disruption based on holidays during the first quarter. So we're excited about what we have in front of us with respect to our ability to continue the success of ZURZUVAE in Q1.

我想補充的是，從第一年全年的觀察來看，我們知道這是一個促銷反應靈敏的市場。當我們在 2024 年第四季增加銷售人員時，我們發現 12 月份的銷售天數減少了，而且由於假期的原因，11 月份的銷售天數也減少了。我們預計第一季不會因假期而出現此類中斷。因此，我們對我們在第一季延續 ZURZUVAE 成功的能力感到非常興奮。

Vikram Purohit, Morgan Stanley.

摩根士丹利的維克拉姆·普羅希特（Vikram Purohit）。

Hi. Thanks for taking our question. I wanted to dig a little bit deeper on the sales force expansion -- and also this is Morgan on the phone for Vikram.

你好。感謝您回答我們的問題。我想更深入地探討一下銷售隊伍的擴張問題，這是摩根 (Morgan) 為維克拉姆 (Vikram) 接聽的電話。

So for this recent sales force expansion, how significant of a sales bump are you anticipating over time and how quickly does the addition of reps to the field result in incrementally higher revenues? And then additionally, how many reps were added through the last round of expansion and how large is the field force currently sitting? Thank you.

那麼，對於最近的銷售隊伍擴張，您預計隨著時間的推移，銷售量將有多大的增長，以及銷售代表的增加將多快帶來收入的逐步增加？另外，透過上一輪擴張增加了多少銷售代表，目前現場人員規模有多大？謝謝。

Yeah, Morgan. Thanks for stepping in for Vikram. So I can give you some color on what you're asking, but we're not giving guidance or specifics. So as Chris noted, we increased our sales force in the fourth quarter. So we had them in place for the entire fourth quarter. And in those territories we expanded, we saw 33% increase. So we can't give go-forward guidance, but that's what we saw in the fourth quarter.

是的，摩根。感謝您接替維克拉姆。因此我可以對你所問的問題提供一些解釋，但我們不會提供指導或具體資訊。正如克里斯所說，我們在第四季度增加了銷售人員。所以我們在整個第四季都實施了這些措施。在我們擴張的地區，我們看到了 33% 的增幅。因此，我們無法提供未來指引，但這就是我們在第四季看到的情況。

We're very confident that the combined sales force extension will continue to be accelerant to our launch, and we'll see quarter-to-quarter demand and revenue growth going forward.

我們非常有信心，合併後的銷售隊伍的擴大將繼續加速我們的上市，並且我們將看到未來季度的需求和收入成長。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Hi, yes, this is Alex on for David. I have one question for you. On the back of the corporate restructure last quarter and the extended cash runway, do you think you're at all constrained in terms of how much commercial support you can put behind ZURZUVAE, particularly relative to the support that Biogen provides for the assets? Thank you.

嗨，是的，我是 Alex，為 David 主持。我要問你一個問題。在上個季度的公司重組和現金流延長的背景下，您是否認為您在為 ZURZUVAE 提供的商業支援方面受到了限制，尤其是相對於 Biogen 為資產提供的支援而言？謝謝。

Yeah. I don't think we're constrained at all. And as we've talked about from the beginning of ZURZUVAE launch, we thought really big about the opportunity with PPD. Again, we believe that ZURZUVAE has blockbuster potential. Epidemiologically, there's about 0.5 million women a year that have symptoms of PPD, less than half of those are diagnosed, and even less are treated. So the opportunity here is significant.

是的。我認為我們根本沒有受到任何限制。正如我們在 ZURZUVAE 推出之初就談到的那樣，我們非常重視 PPD 帶來的機會。再次，我們相信 ZURZUVAE 具有轟動一時的潛力。從流行病學角度來看，每年約有 50 萬名女性出現產後憂鬱症症狀，但其中只有不到一半的女性被診斷，而接受治療的女性則更少。所以這裡的機會非常重要。

We're thinking big about the opportunity. We continue to focus and scale with success. We've scaled with success based upon 2024 volts into 2025. And we can continue to do so, where we believe that the dollar spent will result in immediate improvement in demand and revenue. So we don't feel we're constrained at all.

我們正在認真考慮這一機遇。我們將繼續集中精力，不斷取得成功。我們已經成功地將 2024 伏特電壓擴展到 2025 伏特電壓。我們可以繼續這樣做，我們相信所花的錢將立即帶來需求和收入的改善。因此我們根本不覺得受到任何限制。

Paul Matteis, Stifel.

保羅·馬泰斯（Paul Matteis），Stifel。

Hey. Thanks for taking my question. On the pipeline, Barry, can you just talk a little bit more about how you selected these indications? And I guess, taking a step back, neurodevelopmental disorders is an extremely challenging area for drug development, and you probably picked one of the hardest. DEEs, those are the toughest to treat epilepsies. Why are these the best uses for capital for Sage going forward over other alternatives? Thanks.

嘿。感謝您回答我的問題。關於管道，Barry，您能否再稍微談談您是如何選擇這些適應症的？我想，退一步來說，神經發育障礙對​​於藥物開發來說是一個極具挑戰性的領域，而你可能選擇了最困難的領域之一。DEE 是治療癲癇最困難的治療方法。與其他替代方案相比，為什麼這些是 Sage 未來資本的最佳用途？謝謝。

Paul, I'll start, and I'll ask Laura to jump in. So as we've talked about, we took a hard look at really the last decade of development of Sage and decided to focus on neurodevelopment, neuropsych with molecules that have pharmacologic properties that expresses the learnings we have, and I'll let Laura talk about those a little bit more. So we think we've got the right molecules going forward and the right kind of match to the pharmacology of these diseases. But Laura, do you want to talk more about that?

保羅，我先開始，然後我會請蘿拉加入。正如我們所討論的，我們認真回顧了 Sage 過去十年的發展，並決定專注於神經發育和神經心理學，利用具有藥理特性的分子來表達我們所掌握的知識，我會讓 Laura 再多談一點這些內容。因此我們認為我們已經獲得了正確的分子以及與這些疾病的藥理學正確的匹配。但是勞拉，你想進一步談談這件事嗎？

Yeah. Sure. As we thought about the pharmacology of the molecules in our pipeline, we realized that they would be a good fit for disorders like neurodevelopmental disorders or NDDs and for the DEEs. For the DEEs, in particular, we have a lot of pre-clinical data looking at GABAA PAMs and animal models of seizure disorder, and we've seen efficacy across a number of GABAA PAMs including SAGE-324.

是的。當然。當我們思考我們研發管道中分子的藥理學時，我們意識到它們非常適合治療神經發育障礙或 NDD 以及 DEE 等疾病。特別是對於 DEE，我們有大量針對 GABAA PAM 和癲癇症動物模型的臨床前數據，並且我們已經看到了包括 SAGE-324 在內的多種 GABAA PAM 的療效。

We also know that another GABAA PAM, Ganaxolone, has demonstrated efficacy in one of the DEEs. So there's a strong evidence base there that suggests that we could be successful in moving SAGE-324 for an indication like that.

我們也知道，另一種 GABAA PAM，Ganaxolone，已在其中一種 DEE 中顯示出功效。因此，有強有力的證據表明我們可以成功地將 SAGE-324 用於這樣的適應症。

With regard to the neurodevelopmental disorders, one of the reasons that drug development in this space has been so challenging is that people are trying to treat the core symptoms of the disorder like autism. They're trying to treat the communication difficulties.

對於神經發育障礙，該領域藥物開發如此具有挑戰性的原因之一是人們試圖治療該障礙的核心症狀，例如自閉症。他們正在努力解決溝通困難。

The approach that we're taking is different. We're really looking to address the behavioral symptoms associated with these disorders, and we believe based on the biology of GABAA PAMs and how they work that we are likely to have improvements in anxiety and sleep in sensory hypersensitivity and in irritability. And so, we believe strongly that moving SAGE-319 forward for an NDD such as autism is warranted based on the data that we have.

我們採取的方法不同。我們確實希望解決與這些疾病相關的行為症狀，我們相信，基於 GABAA PAM 的生物學特性及其作用原理，我們可能會改善感覺過敏和易怒等焦慮和睡眠問題。因此，我們堅信，根據我們掌握的數據，推動 SAGE-319 用於治療自閉症等 NDD 是合理的。

Yeah, I'd add that -- and we'll share more in the quarters to come, but we're also taking a capital allocation approach where we can get answers relatively quickly versus the way that Sage has developed for the last decade. And Paul, you and I talked about this in January, the NMDA NAMs are an incredibly well-validated target relative to the PAMs. We took a big swing and didn't see the results we wanted.

是的，我想補充一點——我們將在接下來的幾個季度分享更多信息，但我們也採取了資本配置方法，與 Sage 在過去十年的發展方式相比，我們可以相對較快地得到答案。保羅，你和我在一月份討論過這個問題，相對於 PAM，NMDA NAM 是一個經過充分驗證的目標。我們付出了巨大的努力卻沒有得到想要的結果。

Right. And Barry, when do you think you could get POC for each of these?

正確的。巴里，你認為什麼時候才能獲得上述每個項目的 POC？

We'll share more in the future. So for SAGE-319, we'll have results from our multiple ascending dose later this year; we said late this year. What that will tell us is, do we have an efficacy profile that looks good but differentiated from the balance PAMs, and more importantly or as importantly, do we see a broader therapeutic index, in other words, less CNS effects? So we'll have that at the end of the year.

我們將來會分享更多。因此對於 SAGE-319，我們將在今年稍後獲得多次遞增劑量的結果；我們說的是今年晚些時候。這將告訴我們，我們是否擁有一個看起來不錯但又與平衡 PAM 有所區別的功效概況，更重要的是，我們是否看到更廣泛的治療指數，換句話說，更少的 CNS 影響？因此我們將在年底實現這一目標。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi, thanks for taking my question. Sorry if you already addressed it in your prepared remarks, but can you just talk a little bit about the dynamics of inventory? What have they been, and how should we be thinking about incorporating that into our estimates for 2025? Thanks.

你好，謝謝你回答我的問題。抱歉，如果您已經在準備好的發言中提到了這一點，但您能否稍微談談庫存動態？它們是什麼？ 我們應該如何考慮將其納入我們對 2025 年的估計中？謝謝。

Yeah, Tazeem, we did. But let me start. I'll hand it over to Chris. So we believe the most important metric to look at is shipments. That's the true measure of demand. That is when ZURZUVAE exits the specialty pharma and gets into the hands of moms specifically directly to their home. And the fact that we saw over 20% growth quarter to quarter with far less days educating healthcare providers in the field is a very strong sign. The revenue is more a function of inventory management.

是的，塔澤姆，我們做到了。但請讓我開始。我會把它交給克里斯。因此我們認為最重要的指標是出貨量。這才是真正的需求衡量標準。從那時起，ZURZUVAE 就脫離了專業製藥的範疇，直接進入了媽媽們的手中。事實上，我們看到季度環比增長超過 20%，而且用於現場培訓醫療保健提供者的時間卻大大減少，這是一個非常強烈的信號。收入更多取決於庫存管理。

Chris, do you want to highlight where that supply chain (multiple speakers) ?

克里斯，你想強調供應鏈在哪裡（多位發言者）？

Yeah. I mean inventory is managed, as Barry noted, at the specialty pharmacy level and at the wholesaler level, and I think what we see is that at both of those points, you have organizations trying to manage inventory based on what's happened in the past and their expectation for the future. And there's variability in how they think about assessing channel dynamics in order to make those decisions.

是的。我的意思是，正如巴里所說，庫存是在專業藥房和批發商層面進行管理的，我認為我們看到的是，在這兩個層面，組織都試圖根據過去發生的情況和對未來的預期來管理庫存。並且，他們在評估管道動態以做出這些決策的方式上存在差異。

So as you noted, there's fluctuations in how they see inventory, and it's most important instead of looking at inventory and the implications that it has on revenue to really focus in on demand, which is the truest way of assessing the demand for this product, the interest in this product on behalf of physicians and the women that they're trying to treat.

正如您所說，他們對庫存的看法存在波動，最重要的是不要關注庫存及其對收入的影響，而要真正關注需求，這是評估該產品需求的最真實方式，以及醫生和他們試圖治療的女性對該產品的興趣。

Right. And we said this before but just for clarity, revenue is a shipment to the wholesaler, and that's when revenue is recorded. It's then pulled through the specialty pharm and then again shipped to mom's house. So that whole supply chain, the inventory dynamic fluctuates there.

正確的。我們之前就說過，但為了清楚起見，收入是出貨給批發商的，這就是記錄收入的時候。然後它被送往專科藥房，再次運送到媽媽的家。因此整個供應鏈的庫存動態都會波動。

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Hi, good evening. Thanks for taking my question. Just with regards to the additional investments that you highlighted, whether it's through DTC and some of the other sort of media and education efforts, can you try and quantify by how much you're increasing that? And with regards to the sales force expansion, is there additional expansion anticipated later this year? And at this point, in terms of investments from Sage and Biogen, is it sort of about equal or if you could sort of share any details on Biogen's role in that, that'll be helpful. Thank you.

嗨，晚上好。感謝您回答我的問題。關於您強調的額外投資，無論是透過 DTC 還是其他類型的媒體和教育工作，您能否嘗試量化您增加了多少投資？關於銷售隊伍的擴張，今年稍晚是否預計還會進一步擴張？目前，就 Sage 和 Biogen 的投資而言，它們是否差不多，或者您是否可以分享一些有關 Biogen 在其中所扮演的角色的詳細信息，這將會很有幫助。謝謝。

Thanks, Nadia. I'll start and I'll ask Chris to come in. And again, we can give more color than detailed specifics, because we're not giving guidance. What I said is based on the success of 2024, we've entered 2025 with an aligned commercialization plan, which is a 50-50 COCO plan. So for every $1 spent, we're each spending $0.50. We're both expanding sales force, and we're both expanding efforts across all the other dimensions that I highlighted.

謝謝，納迪亞。我先開始，然後請克里斯進來。再說一次，我們可以給出更多的細節而不是詳細的細節，因為我們沒有提供指導。我所說的是基於 2024 年的成功，我們已經進入 2025 年，並​​製定了一致的商業化計劃，即 50-50 的 COCO 計劃。因此每花費 1 美元，我們每個人就花費 0.50 美元。我們都在擴大銷售隊伍，我們也在加大我在強調的所有其他方面的努力。

Chris, any other color to add?

克里斯，還有其他顏色要補充嗎？

What I would add is the sales force expansion and the investment in non-personal promotion, we're amidst that. So we're investing in the sales force expansion now and investing in, as I mentioned earlier, things like social media and the influencer campaign and getting ready to kick off DTC, particularly through channels like connected TV, where we can be very precise around our ability to reach certain populations that are actually suffering with PPD using DTC as well as disease state awareness to really not only highlight the importance of medication like ZURZUVAE but the importance of screening and diagnosis and when you have symptoms presenting those symptoms to your clinician, whether it's an OB-GYN, a psychiatrist, or a PCP. So all of those things are coming together right now, and we believe will have impact as we continue to roll those out.

我想補充的是，我們正處於銷售隊伍擴張和非個人促銷的投資之中。因此，我們現在正在投資擴大銷售隊伍，正如我之前提到的，我們正在投資社交媒體和影響力活動等方面，並準備啟動 DTC，特別是透過聯網電視等管道，在這些管道中，我們可以非常精確地接觸到實際上患有 PPD 的特定人群，使用 DTC 以及疾病狀態意識，不僅真正強調了 ZURZUVAE 等藥物治療的重要性，還強調了藥物篩檢和患者的精神症狀，無論是精神科醫師的重要性。所以，所有這些事情現在都匯集在一起，我們相信，隨著我們繼續推出這些事情，它們將會產生影響。

Brian Abrahams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

Hi, this is Kevin on for Brian. Thanks for taking our questions. Can you maybe talk a little bit about whether there's certain characteristics for OB-GYNs that currently are not prescribing ZURZUVAE? Does it mostly come down to awareness, or is there some other factor at play, maybe geographical location? Thank you very much.

大家好，我是 Kevin，代表 Brian。感謝您回答我們的問題。您能否稍微談談是否存在某些婦產科醫師目前不開立 ZURZUVAE 處方的情況？這主要取決於意識嗎，還是有其他因素在起作用，例如地理位置？非常感謝。

Yeah, Kevin. Let me ask Chris to comment on that.

是的，凱文。讓我請克里斯對此發表評論。

Yeah. So I think as Barry noted, 80% or nearly 80% of our prescribers are OB-GYNs, who are on the forefront of care. These are the clinicians who see women throughout their peripartum journey and who have the best lens on what it is that they need when they express the signs and symptoms of PPD.

是的。因此我認為正如巴里所說的那樣，我們 80% 或近 80% 的處方人員都是婦產科醫生，他們處於醫療護理的最前線。這些臨床醫生會在整個圍產期觀察女性，並且最清楚當她們表現出產後憂鬱症的徵兆和症狀時需要什麼。

What we see is that when we have an opportunity to engage in OB-GYN with the safety and the efficacy profile of ZURZUVAE, and they have the opportunity to try the medication that they respond very positively to that experience with more than 60% of those OB-GYNs becoming multiple prescribers of the medication. So what I think it comes down to is just our ability to really increase our reach and to increase our frequency in order to deliver what is very compelling messaging from a product that is performing in the real world setting much like it did in ROBIN and SKYLARK, our Phase 3 pivotal clinical studies. So very excited about the opportunity, as I noted, about increasing the size of the sales force and the investment in non-personal ultimately, to get to the broader audience of clinicians that we can reach.

我們看到，當我們有機會讓婦產科醫生了解 ZURZUVAE 的安全性和有效性時，他們有機會嘗試這種藥物，他們對這種體驗的反應非常積極，超過 60％ 的婦產科醫生多次開立該藥物的處方。因此，我認為歸根結底是我們真正擴大影響力和增加頻率的能力，以便透過在現實世界中表現良好的產品傳遞非常引人注目的信息，就像在我們的第 3 階段關鍵臨床研究 ROBIN 和 SKYLARK 中所做的那樣。因此，正如我所說，我們對這個機會感到非常興奮，我們最終將擴大銷售團隊的規模，並增加對非個人方面的投資，以接觸到我們可以接觸到的更廣泛的臨床醫生受眾。

Yeah, Kevin, once an OB-GYN office has been educated and uses ZURZUVAE, we're seeing a significant amount of rewriting and a significant amount of more -- over 300% actually more PPD in that practice area. So we're excited as 2025 unfolds and we see the sales force expansion having an impact.

是的，凱文，一旦婦產科辦公室接受了教育並使用 ZURZUVAE，我們就會發現大量重寫工作，而且該實踐領域的 PPD 實際上增加了 300% 以上。因此，我們對 2025 年的到來感到興奮，並看到銷售團隊的擴張產生影響。

Laura Chico, Wedbush Securities.

勞拉‧奇科（Laura Chico），韋德布希證券公司。

Hello. This is Dylan on for Laura Chico. Thanks very much for taking our question. Just one on PPD. Do you anticipate any near-term revisions to treatment guidelines in the PPD setting from perhaps ACOG or AAP? I'm wondering how this might accelerator impacts commercial uptake.

你好。這是 Dylan 為 Laura Chico 表演的。非常感謝您回答我們的問題。PPD 上只有一個。您是否預期 ACOG 或 AAP 等機構近期會對 PPD 治療指引做出修訂？我想知道這種加速器會如何影響商業應用。

Yeah, Dylan, I'll start. ACOG, we've got phenomenal guidelines. Before ZURZUVAE was approved, there was ACOG guidelines that instructed OB-GYNs and their office to screen, diagnose, and treat with pretty easy-to-use tools that don't require special training. And ZURZUVAE is the drug to specifically mentioned in guidelines.

是的，迪倫，我先開始。美國婦產科醫師協會（ACOG），我們有優秀的指導方針。在 ZURZUVAE 獲得批准之前，美國婦產科醫師學會 (ACOG) 曾指導婦產科醫師及其辦公室使用非常易於使用且不需要特殊培訓的工具進行篩檢、診斷和治療。而ZURZUVAE是指引中特別提到的藥物。

So I've launched a lot of drugs in my day. It doesn't get any better than having your drug mentioning guidelines before you launch. And ACOG's been a great partner.

所以我當時推出了很多藥物。在產品上市前，沒有什麼比獲得藥品提及指南更好的了。ACOG 一直是我們非常出色的合作夥伴。

In terms of other congresses, we continue to work with others to update guidelines. The fact that ACOG did it so quickly is really helpful, because as we've already talked about, our prime audience here because they're at the beginning of the patient journey are OB-GYNs.

對於其他大會，我們將繼續與其他大會合作更新指導方針。美國婦產科醫師協會 (ACOG) 如此迅速地採取行動確實很有幫助，因為正如我們已經討論過的，我們的主要受眾是婦產科醫生，因為他們正處於患者旅程的開始階段。

Yeah. Barry, what I would add, I think, as you noted, the ACOG guidelines were in place in and around the time of our approval and launch. There were a number of tailwinds, the ACOG guidelines being one of those tailwinds, the media behind it, the paired ecosystem and how they really have enabled broad and equitable access to this medication. So a lot of things really supporting this launch out of the gate that really augment what we've been able to take advantage of with the ACOG guidelines.

是的。巴里，我想補充的是，正如你所說，ACOG 指南在我們批准和發佈時就已經制定好了。有許多順風因素，美國婦產科醫師學會 (ACOG) 指南就是其中之一，其背後還有媒體、配對的生態系統以及它們如何真正實現了廣泛和公平地獲得這種藥物。因此，很多事情確實為這次發射提供了支持，這些事情確實增強了我們能夠利用 ACOG 指南的優勢。

Douglas Tsao, H.C. Wainwright.

曹國偉，H.C.溫賴特。

Hi, good afternoon. Thanks for taking the question. Just curious, you've obviously had a lot of success getting the OB-GYNs to prescribe. Are you surprised that you haven't had more penetration with psychs? Thank you.

嗨，下午好。感謝您回答這個問題。只是好奇，你顯然在讓婦產科醫生開處方方面取得了很多成功。您對自己未能與心理學有更深入的了解感到驚訝嗎？謝謝。

Yeah. Doug, thanks for the question. So we're actually -- we're not surprised by the dynamic we're seeing at all. As we talked about, strategically, in any drug launch, you want to focus on the front-end of the patient journey. In this case, that front-end is OB-GYNs, and we're seeing tremendous penetration there and tremendous uptake in OB-GYNs.

是的。道格，謝謝你的提問。因此我們實際上——我們對所看到的動態一點也不感到驚訝。正如我們所討論的，從戰略上講，在任何藥物發布中，你都希望專注於患者旅程的前端。在這種情況下，前端是婦產科醫生，我們看到婦產科醫生在那裡有著巨大的滲透力​​和巨大的吸收力。

As we said, once an OB-GYN is educated about ZURZUVAE and uses ZURZUVAE, we're seeing significantly more rewriting and coverage of this disease in their practice. So that's what we want to see.

正如我們所說的，一旦婦產科醫生了解了 ZURZUVAE 並使用了 ZURZUVAE，我們就會看到他們在實踐中對這種疾病有更多的改寫和報告。這正是我們希望看到的。

Now, as Chris highlighted, of course, there are other healthcare providers that we want educated on PPD and ZURZUVAE, psychs, primary care because not every OB-GYN picks up every mom and not every woman develops symptoms in the course of being seen by their OB-GYN. It could happen two or three months after giving birth. So we are seeing the kind of dynamic exactly as we expected, and as we continue to expand use, OB-GYNs will remain the front-end of coverage here and care.

現在，正如克里斯所強調的，當然，我們希望其他醫療保健提供者也接受有關 PPD 和 ZURZUVAE 的教育，包括心理和初級保健，因為並不是每個婦產科醫生都會接診每個媽媽，也不是每個女性在接受婦產科醫生診治的過程中都會出現症狀。這可能發生在分娩後兩三個月。因此，我們看到的動態正如我們所預料的那樣，隨著我們繼續擴大使用，婦產科醫生將繼續處於覆蓋和護理的最前端。

Okay, great. And just as a follow-up, the question I've gotten from investors in terms of 319 and the SAD and MAD data that you'll have this year, I'm just curious, I think it'd be helpful to provide some additional perspective on beyond just the exposure, but what types of information you'll get from that study that will give people confidence that you have an active drug. I mean, obviously, you won't have clinical data in terms of patients, but just in terms of what you'll see that should give people increased confidence that this will ultimately have success in the clinic. Thank you.

好的，太好了。作為後續問題，投資者問我有關 319 以及您今年的 SAD 和 MAD 數據的問題，我很好奇，我認為提供一些除了曝光之外的額外觀點會很有幫助，但是您將從這項研究中獲得哪些類型的信息，讓人們相信您擁有一種有效的藥物。我的意思是，顯然你不會有患者的臨床數據，但就你所看到的情況而言，這應該會讓人們更有信心這最終會在臨床上取得成功。謝謝。

Yeah, good point, Doug. Laura, why don't you talk about the EEG signal we'll have and then the safety database, which is both of which will be very helpful instructing the path forward?

是的，道格，說得好。勞拉，為什麼不談談我們將擁有的腦電圖訊號以及安全資料庫呢？

So as we mentioned, we're conducting a Phase 1 program, and it includes a SAD study and a MAD study, very conventional. The primary endpoints, of course, are safety and tolerability. But we know from pre-clinical data using extrasynaptic preferring molecules that there's a different EEG signature that you can see in animals, and that different EEG signature represents a different type of engagement of brain circuitry. We are able to look in the clinic using EEG to look for that same signature. And so when we come to the end of these studies, we'll be able to say whether that differential signal that reflects different activation of brain circuitry that we see pre-clinically also happens in patients.

正如我們所提到的，我們正在進行第一階段的計劃，其中包括一項 SAD 研究和一項 MAD 研究，非常常規。當然，主要終點是安全性和耐受性。但我們從使用突觸外偏好分子的臨床前數據中了解到，在動物身上可以看到不同的腦電圖特徵，並且不同的腦電圖特徵代表不同類型的大腦迴路參與。我們能夠在診所使用腦電圖來尋找相同的特徵。因此，當我們完成這些研究時，我們將能夠說出我們在臨床前看到的反映大腦迴路不同活化的差異訊號是否也發生在患者身上。

Uy Ear, Mizuho.

黃耳、瑞穗。

Hey, guys. Thanks for taking our question. Just breaking away a bit from the other questions. Just wondering what -- maybe could you help us understand a little bit what's going on with the agreement with your collaborator in Japan, Shionogi? Are you expecting any milestones or anything to that effect? I think they are expecting -- or there could be a decision on their MDD application sometime in September. Thanks.

嘿，大家好。感謝您回答我們的問題。只是與其他問題稍微脫離。只是想知道——也許您能幫助我們了解一下您與日本合作夥伴 Shionogi 達成的協議的情況嗎？您是否期待任何里程碑或類似的事情？我認為他們正在等待——或者可能會在九月某個時候對他們的 MDD 申請做出決定。謝謝。

Yeah. Absolutely. Thanks for going there. So I'll come and then Chris can talk about milestones. So what our Japanese friends have shared is that they expect a decision on MDD from the Japanese FDA later this year. And it's an MDD indication, which in Japan also includes women that have given birth. So it's folded under there as well.

是的。絕對地。謝謝你去那裡。所以我會來，然後克里斯可以談論里程碑。因此，我們的日本朋友表示，他們預計日本 FDA 將在今年稍後就 MDD 做出決定。這是一種 MDD 指徵，在日本，這也包括已生育的女性。所以它也折疊在那裡。

Chris, do you want to talk about the milestones?

克里斯，你想談談里程碑嗎？

Yeah, sure, Barry. If approved, we're entitled to receive regulatory and commercial milestones from Shionogi. Regulatory milestones amount to a total of approximately $55 million, of which a portion would be achieved upon MDD approval. Now there are additional commercially related milestones, including upon first commercial sale. Currently, no milestones have been assumed in our cash runway expectations into 2027.

是的，當然，巴里。如果獲得批准，我們有權從鹽野義獲得監管和商業里程碑。監管里程碑總額約為 5500 萬美元，其中一部分將在獲得 MDD 批准後實現。現在還有其他商業相關的里程碑，包括首次商業銷售。目前，我們對 2027 年的現金流量預期尚未設定任何里程碑。

Yeah. So if they're successful in getting approval, and we get the milestones and royalties, that's upside to our cash runway.

是的。因此，如果他們成功獲得批准，並且我們獲得里程碑和特許權使用費，那麼這對我們的現金流來說就是有利的。

Could you maybe just speak a little bit about the potential opportunity in Japan? For what reasons (multiple speakers)

您能否稍微談談日本的潛在機會？出於什麼原因（多位發言者）

I think what I can say the way Japan works, and you need to talk to them about it is if they get the KOLs behind them, they should have a pretty interesting commercial uptake. But we have to talk to them directly about what their expectations are.

我想我可以說日本的運作方式是，你需要和他們談談，如果他們得到KOL的支持，他們應該會有一個相當有趣的商業吸收。但我們必須直接與他們討論他們的期望。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi. Thanks for taking the question. Could you give a sense of how sensitive the market is to marketing to physicians versus raising awareness among inpatients? And are scripts tending to come for patients who are already aware of ZURZUVAE and asking about it or more about patients who may not have heard of it before?

你好。感謝您回答這個問題。您能否介紹一下市場對於向醫師行銷以及提高住院病患意識的敏感度如何？並且，處方是否傾向於針對那些已經了解 ZURZUVAE 的患者，並詢問有關該藥物或更多可能以前沒有聽說過該藥的患者？

Yeah, Joel, I'll ask Chris to come in.

是的，喬爾，我會請克里斯進來。

So as I've already said, this is a promotionally responsive market. We see that whether it is the sales force or it is non-personal promotion and the various different tactics that we talked about that really there is an impact of those. In terms of, is it coming from physician behavior or is it coming from directly engaging with patients either through DTP or DTC, the sense that we have is it's coming from really a balance of both of those things, that this is a market in which, as Barry noted, we have an activated group of healthcare professionals, OB-GYNs, who are really willing recipients of this message and then are subsequently not only treating but screening and diagnosing at a higher level.

正如我已經說過的，這是一個促銷響應的市場。我們發現，無論是銷售團隊或非個人促銷，以及我們談到的各種不同策略，確實都會產生影響。至於它是來自醫生的行為，還是透過 DTP 或 DTC 直接與患者接觸，我們的感覺是，它實際上來自這兩者的平衡，正如 Barry 指出的那樣，在這個市場中，我們擁有一群活躍的醫療保健專業人士、婦產科醫生，他們真正願意接受這一信息，隨後不僅進行治療，還在更高層次上進行篩檢和診斷。

We also know that this is a market where patients are activated with the information that we provide. And they're engaging their healthcare professionals in informed discussions that enable those clinicians to provide them with perspective on not only the importance of treating PPD but using a medication like ZURZUVAE. So we believe that what we're doing right now is not only launching ZURZUVAE, but we're building an opportunity, expanding opportunity through increased screening and diagnosis through education and disease state awareness.

我們也知道，這是一個患者可以透過我們提供的資訊來啟動的市場。他們正在與醫療保健專業人員進行知情討論，使這些臨床醫生不僅能夠為他們提供有關治療 PPD 的重要性的觀點，而且還能使用 ZURZUVAE 等藥物。因此，我們相信，我們現在所做的不僅是推出 ZURZUVAE，我們正在創造機會，透過教育和疾病狀況意識增加篩檢和診斷來擴大機會。

Sumant Kulkarni, Canaccord.

Sumant Kulkarni，Canaccord。

Good afternoon. Thanks for taking our question. Given what we know about the size of the PPD market in terms of patient and prescriber numbers, do you believe this collaboration is required to get commercialization right on ZURZUVAE? And how would you characterize the sales force's level of focus with all the stuff that's going on in the background?

午安.感謝您回答我們的問題。鑑於我們對 PPD 市場規模（包括患者和處方者數量）的了解，您是否認為此次合作對於 ZURZUVAE 的商業化至關重要？您如何描述銷售人員對幕後發生的所有事情的關注程度？

Yeah. So the collaboration exists, so that's how we're operating. And I can tell you that on a day-to-day basis, the sales force and both commercialization teams are laser focused in helping as many moms in 2025 as possible. There are no distractions.

是的。所以合作是存在的，這就是我們的運作方式。我可以告訴你，在日常工作中，銷售團隊和兩個商業化團隊都專注於在 2025 年幫助盡可能多的媽媽。沒有任何干擾。

Joon Lee, Truist Securities.

Joon Lee，Truist Securities。

Thanks for taking our questions. What proportion of the patients who get ZURZUVAE are getting it as their first-line therapy? And for those who are diagnosed with PPD but getting some form of pharmacotherapy other than ZURZUVAE, what are some of the challenges there? Is this an issue of access or something else like perception as a novel drug with relatively less safety data? Thank you.

感謝您回答我們的問題。接受 ZURZUVAE 治療的患者中有多少比例將其作為第一線治療？對於那些被診斷患有 PPD 但接受 ZURZUVAE 之外的其他藥物治療的人來說，他們面臨哪些挑戰？這是獲取途徑的問題，還是其他問題，例如人們對新藥的認知度，以及其安全性數據相對較少？謝謝。

Yeah, Joon, thanks. Chris, you want to start, and then I'll loop back to fill in some of the other color.

是的，Joon，謝謝。克里斯，你想開始，然後我會循環回來填充一些其他顏色。

Yeah. So what we've said is that with respect to all of the work that we've done with not only payers but also with physicians, we want to ensure broad and equitable access. And in doing so, this has enabled physicians to use this medication, ZURZUVAE, as a first-line treatment.

是的。因此，我們所說的是，對於我們與付款人以及醫生所做的所有工作，我們都希望確保廣泛和公平的機會。這樣一來，醫生就可以使用這種藥物 ZURZUVAE 作為第一線治療。

What we've communicated in our prepared remarks is now that more than 70% of those that are receiving the medication through the targeted HCPs that we're calling on, they're able to get this medication as a first-line medication, which is really incredible when you think about it, to have that degree of first-line use right out of the gate. So to me, I think that's something really to reflect on not only the work that we've done with physicians but also with payers.

我們在準備好的評論中已經傳達的信息是，現在透過我們呼籲的目標 HCP 獲得藥物的患者中，超過 70% 能夠將這種藥物作為一線藥物，想想看，一開始就具有這種程度的一線使用率，真是令人難以置信。所以對我來說，我認為這不僅要反映我們與醫生合作所做的工作，還要反映我們與付款人合作所做的工作。

Now in terms of other patients who may not be getting this in the first line, there are patients who come through who have a prior history on other antidepressants because perhaps they've been diagnosed with the condition by a clinician in the past. So those that aren't getting it in the first-line position aren't getting it, because they're being excluded from getting it. They typically come forward on another medication, and that's the rationale for it.

現在，對於其他可能不會在第一線接受這種治療的患者來說，有些患者曾經使用過其他抗憂鬱藥，因為他們可能在過去被臨床醫生診斷出患有這種疾病。因此，那些沒有在第一線獲得該獎項的人沒有獲得該獎項，因為他們被排除在外了。他們通常會選擇另一種藥物，這就是其理由。

As you said, Joon, in any novel drug launch, you have to overcome historical bias. Someone was used to using something one way. They've got to understand ZURZUVAE and how to use it.

正如你所說，Joon，在任何新藥的推出中，你都必須克服歷史偏見。有人習慣以某種方式使用某物。他們必須了解 ZURZUVAE 及其使用方法。

We're certainly seeing, as we highlighted, tremendous insurance coverage and very little, if any, out-of-pocket expenses. So it really is about historical bias more than anything else to continue to move to front-line. And just to emphasize, as Chris said, for those that we're targeting me, we've educated, we've engaged, we're seeing significant front-line use for ZURZUVAE.

正如我們所強調的，我們確實看到，保險覆蓋範圍非常廣，而自付費用卻很少（如果有的話）。因此，繼續走向前線實際上更多的是出於歷史偏見。正如克里斯所說，需要強調的是，對於那些我們所針對的對象，我們已經進行了教育，我們已經參與其中，我們看到了 ZURZUVAE 的顯著前線用途。

Marc Goodman, Leerink Partners.

馬克古德曼（Marc Goodman），Leerink Partners。

Hi, this is Basma on for Marc. Thank you for taking our question. Can you provide some color on the gross and net in the quarter, given that there was higher -- greater demand, but the revenue kind of seemed to be flattish, if you compare the fourth quarter to the third quarter?

大家好，我是 Basma，為 Marc 播報。感謝您回答我們的問題。鑑於需求較高（更大），但如果將第四季度與第三季度進行比較，收入似乎持平，您能否提供一些本季毛利和淨利的詳細資訊？

And also, we have another question about, can you tell us now after one year from the launch if any of the treated patients needed to receive more than one treatment course? If so, can you provide some color on the proportion of these patients and whether there has been any pay of pushback. Thank you.

另外，我們還有一個問題，您能否告訴我們，從推出一年後，是否有任何接受治療的患者需要接受多個療程？如果是，您能否介紹一下這些患者的比例以及是否有任何阻力。謝謝。

Yeah. Let me take that kind of in reverse order. So what we've seen and what we're hearing reported back is that the performance of ZURZUVAE in the real world is good or better than we saw in our clinical trials. So it's a rapid and durable response. We're not picking up much of any kind of re-treatment at all. We're seeing that the 14-day course works rapidly and is helping moms, and that response is maintained.

是的。讓我以相反的順序來討論這個問題。因此，我們看到的和聽到的報告是，ZURZUVAE 在現實世界中的表現比我們在臨床試驗中看到的更好或更好。因此這是一種快速而持久的反應。我們根本沒有採取任何形式的再治療。我們看到，為期 14 天的課程效果顯著，對媽媽們有幫助，而且這種反應一直持續著。

In terms of the dynamic, we've talked about this a couple of times. The over 20% demand growth is encouraging in the fourth quarter. The revenue growth is really a matter of sort of channel management inventory, not really a matter of gross to net. And again, we're excited by -- thank you -- we're excited by the start to 2025 and where the launch is going.

就動態而言，我們已經討論過幾次了。第四季超過20%的需求成長令人鼓舞。收入成長其實是一種通路管理庫存的問題，而不是毛收入與淨收入的問題。再次，我們感到非常興奮 - 謝謝 - 我們對 2025 年的開始以及發射地點感到非常興奮。

Thank you. That will conclude the Q&A portion of today's call. With that, I will turn it back over to Mr. Green for closing remarks.

謝謝。今天電話會議的問答部分就到此結束。最後，我將把發言權交還給格林先生，請他作最後發言。

Thanks, Taryn, and thanks, everyone, for joining us on this afternoon to review our results from the fourth quarter and full year 2024. As we look ahead to the ongoing commercialization of ZURZUVAE and PPD and advancements in our focus pipeline, I'm confident we're making important progress for patients. We move forward with investments intended to power ongoing commercial success and create value for shareholders. Thanks, everyone. Have a great evening.

謝謝 Taryn，也謝謝大家今天下午加入我們，回顧我們 2024 年第四季和全年的業績。展望 ZURZUVAE 和 PPD 的持續商業化以及我們重點產品線的進步，我相信我們正在為患者取得重要進展。我們將繼續進行投資，以推動持續的商業成功並為股東創造價值。謝謝大家。祝您有個愉快的夜晚。

This concludes today's call. Thank you, again, for your participation. You may now disconnect and have a great day.

今天的電話會議到此結束。再次感謝您的參與。現在您可以斷開連接並享受美好的一天。