SAGE Therapeutics Inc (SAGE) 2023 Q2 法說會逐字稿

Good morning, and welcome to Sage Therapeutics business update.

早上好，歡迎來到 Sage Therapeutics 業務更新。

(Operator Instructions)

（操作員說明）

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 expressed written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded.

此次電話會議正在 Sage 網站 sagerx.com 的投資者和媒體部分進行網絡直播。本次通話屬於 Sage Therapeutics 的財產，未經 Sage Therapeutics 明確書面同意，嚴禁錄製、複製或傳播本次通話。請注意，此通話正在錄音。

I would now like to introduce Ashley Kaplowitz. Please go ahead.

現在我想介紹阿什利·卡普洛維茨。請繼續。

Good morning, and thank you for joining Sage Therapeutics' conference call to discuss business updates, including the FDA approval of zuranolone now branded in the United States as Zurzuvae as a treatment for results with postpartum depression or PPD.

早上好，感謝您參加 Sage Therapeutics 的電話會議，討論業務更新，包括 FDA 批准 zuranolone 目前在美國的品牌為 Zurzuvae，用於治療產後抑鬱症或產後抑鬱症。

Before we begin, I encourage everyone to go to the Investor and Media section of our website at sagerx.com, where you can find the press release related to today's call as well as slides that we will be reviewing today. 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.

在我們開始之前，我鼓勵大家訪問我們網站 sagerx.com 的投資者和媒體部分，您可以在其中找到與今天的電話會議相關的新聞稿以及我們今天將審查的幻燈片。我想指出的是，我們將根據我們當前的期望和信念做出前瞻性聲明。這些陳述存在一定的風險和不確定性，我們的實際結果可能存在重大差異。請查看今天的新聞稿和我們向 SEC 提交的文件中討論的風險因素，了解更多詳細信息。

We will begin the call with prepared remarks by Barry Greene, our Chief Executive Officer. Then Laura Gault, our Chief Medical Officer, will review the label for Zurzuvae and supporting clinical data. Our Chief Business Officer, Chris Benecchi, will highlight our commercial preparations and launch plans for Zurzuvae and PPD; and Kimi Iguchi, our Chief Financial Officer, will close with a financial update. Jim Doherty, our Chief Development Officer, will also be available during the Q&A portion of the call.

我們將以首席執行官巴里·格林 (Barry Greene) 準備好的講話開始此次電話會議。然後，我們的首席醫療官 Laura Gault 將審查 Zurzuvae 的標籤和支持臨床數據。我們的首席商務官 Chris Benecchi 將重點介紹我們的商業準備工作以及 Zurzuvae 和 PPD 的推出計劃；我們的首席財務官井口基米 (Kimi Iguchi) 將在閉幕式上介紹財務最新情況。我們的首席開發官 Jim Doherty 也將出席電話會議的問答部分。

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

這樣，我現在將把電話轉給巴里。

Thanks, Ashley, and thank you, everyone, for joining us today. This is a historic moment for all women suffering from PPD. On Friday, we and our collaboration partner, Biogen received approval from the FDA for zuranolone now known as Zurzuvae for the treatment of adults with PPD. Zurzuvae is the first and only oral treatment specifically indicated for PPD. Hundreds of thousands of women have been waiting and hoping for this moment. We hear so many devastating stories about the impact of PPD, and many of us have been personally touched by this often neglected condition that's estimated to affect approximately 500,000 women each year. Today, there is a new source of hope.

謝謝阿什利，也謝謝大家今天加入我們。對於所有患有產後抑鬱症的女性來說，這是一個歷史性時刻。週五，我們和我們的合作夥伴 Biogen 獲得 FDA 批准 zuranolone（現稱為 Zurzuvae）用於治療成人 PPD。 Zurzuvae 是第一個也是唯一一個專門針對 PPD 的口服治療藥物。成千上萬的女性一直在等待和期盼這一刻。我們聽過很多關於產後抑鬱症影響的毀滅性故事，我們中的許多人都對這種經常被忽視的疾病深有感觸，據估計，這種疾病每年影響大約 500,000 名女性。今天，有了新的希望。

Before we begin, I'd like to take a moment to sincerely thank the dedicated health care providers, patients, caregivers and advocates who have made today possible, especially the patients who have placed their immense trust in us throughout our clinical trials. We are and will always be an inspiration for us. We applaud your dedication to seeking new treatment options for PPD. I'd also like to comment on the status of our NDA seeking approval for zuranolone in the treatment of major depressive disorder, or MDD. As many of you have seen, late on Friday, we received a complete response letter from the FDA for zuranolone as a treatment for adults with MDD.

在我們開始之前，我想花點時間真誠地感謝敬業的醫療保健提供者、患者、護理人員和倡導者，他們使今天成為可能，特別是在整個臨床試驗過程中對我們給予極大信任的患者。我們現在並將永遠是我們的靈感來源。我們讚揚您致力於尋找新的產後抑鬱症治療方案。我還想評論一下我們尋求批准 zuranolone 治療重度抑鬱症 (MDD) 的新藥申請 (NDA) 的狀況。正如你們許多人所看到的，週五晚些時候，我們收到了 FDA 的完整回复信，內容涉及 zuranolone 作為成人 MDD 的治療方法。

We are devastated for patients and deeply disappointed with the FDA's position in issuing the CRL. We are reviewing feedback from the FDA and evaluating next steps. As we have clarity, we'll share more. Many have questions will affect we can answer and others that we just simply can't at this time. Now just to be clear, progress in treating depression is not keeping pace with the accelerated prevalence and burden deviating disease. Despite current treatment options, people with depression continue to struggle, a change in the treatment paradigm and approval of novel options is desperately needed. Later in the call, Kimi will provide an update on the financial implications given this development.

我們為患者感到悲痛，並對 FDA 發布 CRL 的立場深感失望。我們正在審查 FDA 的反饋並評估後續步驟。當我們弄清楚後，我們將分享更多。許多問題會影響我們的回答，而另一些問題我們目前無法回答。現在需要澄清的是，治療抑鬱症的進展並沒有跟上患病率的加速和疾病負擔偏離的步伐。儘管有目前的治療選擇，抑鬱症患者仍在掙扎，迫切需要改變治療模式並批准新的選擇。在稍後的電話會議中，基米將提供有關這一事態發展所產生的財務影響的最新信息。

For those of us who have been biopharmaceutical industry for decades, going through adversity is an opportunity to come out more lean and agile on the other side. We will work through this. But I can say for now, for Sage is that we'll be making smart, disciplined decisions intended to maintain a robust balance sheet. This is an opportunity to emerge as a stronger company with a refined strategy and a focused approach.

對於我們這些在生物製藥行業工作了幾十年的人來說，經歷逆境是一個在另一方面變得更加精益和敏捷的機會。我們將努力解決這個問題。但我現在可以說，對於 Sage 來說，我們將做出明智、嚴格的決策，以維持穩健的資產負債表。這是一個通過完善的戰略和專注的方法成為一家更強大的公司的機會。

Now turning back to our primary focus for today's call. Following Friday's approval, we have the first and only oral treatment specifically indicated for women with PPD. As a 14-day short course treatment, we believe that Zurzuvae will provide women with PPD, a desperately needed new treatment option with the potential to treat their depressive symptoms quickly without the need for chronic treatment. Given the limited treatment options available for women with PPD, we're excited about the opportunity to bring Zurzuvae to those patients. We expect Zurzuvae to launch and be commercially available in the fourth quarter of 2023 shortly following the completion of scheduling as a controlled substance by the U.S. DEA, which is expected to occur within 90 days of this approval. The widespread national media attention on the approval of Zurzuvae for a treatment of women with PPD reinforces that this is truly a critical milestone given the significant unmet need that currently exists for the treatment of women with this disease.

現在回到我們今天電話會議的主要焦點。繼周五獲得批准後，我們​​有了第一種也是唯一一種專門針對產後抑鬱症女性的口服治療方法。作為一種為期 14 天的短期治療，我們相信 Zurzuvae 將為患有 PPD 的女性提供一種急需的新治療選擇，有可能快速治療她們的抑鬱症狀，而無需長期治療。鑑於患有 PPD 的女性可用的治療選擇有限，我們很高興有機會將 Zurzuvae 帶給這些患者。我們預計 Zurzuvae 將於 2023 年第四季度在美國 DEA 完成作為受控物質的管制後不久推出並上市，預計將在批准後 90 天內進行。 Zurzuvae 獲批用於治療產後抑鬱症(PPD) 受到全國媒體的廣泛關注，這進一步表明，鑑於目前治療患有產後抑鬱症(PPD) 的女性的巨大需求尚未得到滿足，這確實是一個重要的里程碑。

PPD is a serious medical condition. We know that women with PPD often face extreme challenges in their daily lives and with (inaudible), often feeling overwhelmed, anxious and isolated. If less untreated, depressive symptoms can persist beyond a year post part, which can be associated with prolonged maternal morbidity and mortality. While women's PPD can be associated with short-term consequences of newborn, it can also result in long-term developmental, psychological, cognitive and physical ramifications for children. The devastating generational impact of PPD has been often overlooked. With the approval of Zurzuvae, we now have the first and only oral treatment indicated for women with PPD, and we stand ready to help. I want to take a moment to recognize the entire Sage and Biogen teams and our collaborators who brought us to this important day for women with PPD. None of what we do is possible without your hard work, dedication and faltering belief that, together, we have the potential to change the mental health landscape. I thank everyone of you for your contributions towards our mission.

PPD 是一種嚴重的疾病。我們知道，患有產後抑鬱症的女性在日常生活中經常面臨極端的挑戰，並且（聽不清），常常感到不知所措、焦慮和孤立。如果不及時治療，抑鬱症狀可能會在產後持續一年以上，這可能與孕產婦發病率和死亡率延長有關。雖然女性產後抑鬱症可能與新生兒的短期後果有關，但它也可能對兒童的發育、心理、認知和身體產生長期影響。 PPD 對一代人的毀滅性影響常常被忽視。經 Zurzuvae 批准，我們現在擁有第一種也是唯一一種針對產後抑鬱症女性的口服治療方法，我們隨時準備提供幫助。我想花點時間向整個 Sage 和 Biogen 團隊以及我們的合作者致以謝意，他們帶領我們迎來了這一對患有產後抑鬱症的女性來說重要的日子。如果沒有你們的辛勤工作、奉獻精神和堅定的信念，我們所做的一切都是不可能的，因為你們堅信，只要齊心協力，我們就有潛力改變心理健康狀況。我感謝大家為我們的使命做出的貢獻。

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

這樣，我現在將把電話轉給勞拉。

Thanks, Barry, and good morning, everyone. The approval of Zurzuvae in adults with PPD is a pivotal moment for the women who stand to benefit from this important therapy and a great moment for Sage and Biogen. The approval of Zurzuvae further builds the [PAM] foundation laid with Sage's first approved treatment for PPD and reaffirms our commitment to helping mothers in need.

謝謝巴里，大家早上好。 Zurzuvae 獲批用於患有 PPD 的成人患者對於那些將從這一重要療法中受益的女性來說是一個關鍵時刻，對於 Sage 和 Biogen 來說也是一個偉大時刻。 Zurzuvae 的批准進一步奠定了 Sage 首個獲批 PPD 治療藥物奠定的 [PAM] 基礎，並重申了我們對幫助有需要的母親的承諾。

I will start by providing background on Zurzuvae, then I will highlight details of the prescribing information. The mechanism of action of Zurzuvae in the treatment of PPD is thought to be related to its positive allosteric modulation of GABA-A receptors, though the mechanism of action is not fully understood. As the primary inhibitory neurotransmitter, GABA immunobuteric acid or GABA, it's widely distributed throughout the brain. It is present in brain regions functionally associated with mood, decision-making and other behaviors. GABAergic's neurotransmission is vital for normal brain function and evidence shows that GABAergic function may be disrupted in postpartum depression.

我將首先提供 Zurzuvae 的背景，然後我將重點介紹處方信息的詳細信息。 Zurzuvae 治療 PPD 的作用機制被認為與其對 GABA-A 受體的正向變構調節有關，但其作用機制尚不完全清楚。作為主要的抑制性神經遞質，GABA 免疫丁酸或 GABA，廣泛分佈在整個大腦中。它存在於與情緒、決策和其他行為功能相關的大腦區域。 GABA 能的神經傳遞對於正常的大腦功能至關重要，有證據表明 GABA 能的功能可能在產後抑鬱症中受到干擾。

Now I will summarize the clinical data supporting approval of Zurzuvae in women with PPD. The approval is based on data from the NEST clinical development program, which included the SKYLARK and ROBIN study. These studies were Phase III randomized, double-blind, placebo-controlled trials that evaluated a 14-day treatment course of Zurzuvae once daily, used alone or as an adjunct to oral antidepressant therapy in women aged 18 to 45 with PPD. Both studies met the primary end point showing a statistically significant improvement over placebo at day 15 on the 17-item Hamilton Depression Rating Scale, a common measure of depression severity. As shown in the figures, in both the SKYLARK and ROBIN studies and improvement in depressive symptoms was seen as early as day 3 and was maintained at day 45, 4 weeks post treatment. The potential for rapid onset and the magnitude and durability of effect are all very important to women living with PPD.

現在我將總結支持 Zurzuvae 批准用於 PPD 女性的臨床數據。此次批准基於 NEST 臨床開發計劃的數據，其中包括 SKY​​LARK 和 ROBIN 研究。這些研究是 III 期隨機、雙盲、安慰劑對照試驗，評估了 18 至 45 歲患有 PPD 的女性單獨使用或作為口服抗抑鬱治療的輔助藥物 Zurzuvae 每天一次的 14 天治療療程。這兩項研究均達到了主要終點，顯示在第 15 天時，漢密爾頓抑鬱評定量表（17 項抑鬱症嚴重程度的常用衡量標準）較安慰劑有統計學顯著改善。如圖所示，在 SKYLARK 和 ROBIN 研究中，抑鬱症狀早在第 3 天就出現改善，並在第 45 天即治療後 4 週得以維持。快速起效的潛力以及作用的強度和持久性對於患有產後抑鬱症的女性來說都非常重要。

Now I'll provide an overview of the prescribing information, including the safety information. The recommended dosage of Zurzuvae is 50 milligrams taken orally once daily in the evening for 14 days with fat-containing food. The dose may be reduced to 40 milligrams once daily, if CNS-depressant effects occur. Zurzuvae can be used alone or as an adjunct to oral antidepressant therapy. Importantly, there are no contraindications in the label. In terms of safety, the boxed warning state that Zurzuvae causes driving impairment and patients are advised not to drive or engage in other potentially hazardous activities until at least 12 hours after each dose.

現在我將概述處方信息，包括安全信息。 Zurzuvae 的推薦劑量為 50 毫克，每天晚上口服一次，連續 14 天，與含脂肪的食物一起服用。如果出現中樞神經系統抑製作用，劑量可減少至 40 毫克，每日一次。 Zurzuvae 可單獨使用或作為口服抗抑鬱治療的輔助藥物。重要的是，標籤上沒有任何禁忌症。在安全方面，黑框警告指出，Zurzuvae 會導致駕駛障礙，建議患者在每次服藥後至少 12 小時內不要開車或從事其他潛在危險活動。

Patients should also be advised that they may not be able to assess their own driving competence or the degree of impairment caused by Zurzuvae. The label also describes the most common adverse reactions that occurred in at least 5% of patients who received Zurzuvae and at a higher rate than placebo. These were somnolence, nasopharyngitis, dizziness, fatigue, urinary tract infection and diarrhea. And finally, while I am personally disappointed that we will not be able to provide a new treatment option to patients living with MDD today as we had hoped. I am also truly excited that we and Biogen will be offering the first oral rapid-acting short course treatment for women with PPD. I can tell you from my clinical experience, that we have the potential to help a lot of women with this debilitating condition.

還應告知患者，他們可能無法評估自己的駕駛能力或 Zurzuvae 造成的損害程度。該標籤還描述了至少 5% 接受 Zurzuvae 治療的患者發生的最常見不良反應，且發生率高於安慰劑。這些症狀包括嗜睡、鼻咽炎、頭暈、疲勞、尿路感染和腹瀉。最後，雖然我個人對我們無法像我們希望的那樣為重度抑鬱症患者提供新的治療選擇感到失望。我也非常興奮我們和百健（Biogen）將為患有產後抑鬱症的女性提供第一個口服速效短期療法。我可以根據我的臨床經驗告訴您，我們有潛力幫助許多患有這種衰弱病症的女性。

With that, I'll turn the call over to Chris. Chris?

這樣，我會將電話轉給克里斯。克里斯？

Thanks, Laura. I'm excited to be with all of you to share updates on our preparations for the planned commercial launch of Zurzuvae as treatment for adults with PPD.

謝謝，勞拉。我很高興能與大家分享我們計劃商業推出 Zurzuvae 作為成人 PPD 治療藥物的準備工作的最新情況。

Today is the day of celebration, the approval of Zurzuvae reaffirms our call to action and the urgency that exists to bring this critical new treatment to women suffering with PPD. We know that PPD is all too prevalent in our society and the burdens that it places on new mothers can seem insurmountable. With this in mind, we are incredibly excited about the opportunity to bring a novel treatment option to market that we believe brings us closer to transforming the care of women living with PPD. We have been preparing for a potential launch for many months by advancing permitted pre-approval information exchange with payers continuing scientific exchange with health care providers and engaging with patient advocacy organizations.

今天是值得慶祝的日子，Zurzuvae 的批准重申了我們的行動呼籲，以及為患有產後抑鬱症的女性提供這種重要的新療法的緊迫性。我們知道，產後抑鬱症在我們的社會中非常普遍，它給新媽媽們帶來的負擔似乎是難以克服的。考慮到這一點，我們對有機會將一種新穎的治療方案推向市場感到非常興奮，我們相信這將使我們更接近改變患有產後抑鬱症的女性的護理。幾個月來，我們一直在為可能的推出做準備，通過推進與付款人允許的預先批准信息交換，繼續與醫療保健提供者進行科學交流，並與患者倡導組織合作。

Further, we have built an internal team of experienced commercial leaders whose depth and breadth of knowledge and experience to further expand our go-to-market capability. We believe our preparations will enable us to be fully ready to execute the launch of Zurzuvae to treat women with PPD by year-end. The tremendous opportunity exists in PPD with estimates of approximately 1 in 8 women experiencing PPD symptoms in the U.S. each year. That's about 0.5 million women. Today, we know that only about 50% of PPD cases are diagnosed due to an adequate screening or too many women with PPD are not getting the care that they need because of the limited options available to them.

此外，我們還建立了一支由經驗豐富的商業領導者組成的內部團隊，他們的知識和經驗的深度和廣度可以進一步擴大我們的上市能力。我們相信，我們的準備工作將使我們能夠做好充分準備，在年底前推出 Zurzuvae 來治療患有產後抑鬱症的女性。 PPD 存在巨大的機會，據估計，在美國每年大約有八分之一的女性出現 PPD 症狀。大約有 50 萬女性。如今，我們知道，只有約 50% 的產後抑鬱症病例是通過充分的篩查得到診斷的，或者太多患有產後抑鬱症的女性由於可用的選擇有限而沒有得到所需的護理。

With the approval of Zurzuvae, we believe we have the potential to be a first-line therapy and become the standard of care. Our planned launch focus will be on women diagnosed with PPD requiring treatment. We believe the addressable patient population at launch includes those who are newly diagnosed and those experiencing unresolved symptoms despite taking antidepressant treatment. We're not going to stop there with our efforts to help women with PPD. We believe it will also be important to support efforts to increase diagnosis rates in PPD building upon the recent guidelines updated by the American College of Obstetricians and Gynecologists, which recommends increased screening during the pre and postpartum periods.

隨著 Zurzuvae 的批准，我們相信我們有潛力成為一線療法並成為護理標準。我們計劃的推出重點將是被診斷患有產後抑鬱症並需要治療的女性。我們認為，推出時的目標患者群體包括新診斷的患者和儘管接受抗抑鬱治療但症狀仍未解決的患者。我們幫助患有產後抑鬱症的女性的努力不會止步於此。我們認為，根據美國婦產科醫師學會最近更新的指南，支持提高產後抑鬱症診斷率的努力也很重要，該指南建議在產前和產後期間增加篩查。

While thinking big about the unmet need in treating women with PPD, we, alongside our collaboration partner, Biogen, expect to implement a focused launch strategy that can be scaled with success to reach more women with PPD. We plan to leverage our omnichannel capabilities powered by data and predictive analytics that we expect will enable us to efficiently reach a broad base of health care professionals who treat PPD. At launch, we plan to have our focused field sales teams targeting high-prescribing psychiatrists OB/GYN and PCPs who treat women with PPD with a consistent frequency of promotional messages and resources.

在認真考慮治療患​​有產後抑鬱症的女性的未滿足需求的同時，我們與我們的合作夥伴百健（Biogen）一起，期望實施一項有針對性的啟動戰略，該戰略可以成功擴展，以惠及更多患有產後抑鬱症的女性。我們計劃利用由數據和預測分析提供支持的全渠道能力，我們預計這將使我們能夠有效地接觸到治療 PPD 的廣泛醫療保健專業人員。在推出時，我們計劃讓我們的現場銷售團隊以高處方精神科醫生婦產科醫生和主治醫生為目標，以一致的頻率提供促銷信息和資源，以治療患有產後抑鬱症的女性。

Additionally, we plan to advance nonpersonal promotion efforts with digital platforms designed to reach a broad set of HCPs treating these patients. These digital platforms are intended to unite data from our content, media and in-person interactions. It's also vital that our omnichannel work directly reaches women with PPD at launch. Our planned efforts are intended to directly engage these women with education and resources so they are aware of Zurzuvae as a treatment option in PPD and are prepared to have a meaningful discussion about Zurzuvae with their HCPs. HCPs will be a central focus of this planned omnichannel approach as they will ultimately be directly responsible for making the decision to prescribe Zurzuvae in the treatment of women with PPD. We believe early and positive clinical experience and accessibility for women with PPD will be critical to building confidence and accelerating adoption of Zurzuvae in this indication.

此外，我們計劃通過數字平台推進非個人推廣工作，旨在接觸到治療這些患者的廣泛的醫護人員。這些數字平台旨在整合來自我們的內容、媒體和麵對面互動的數據。同樣重要的是，我們的全渠道工作在推出時就直接接觸到患有產後抑鬱症的女性。我們計劃的努力旨在直接讓這些婦女接受教育和資源，以便她們了解 Zurzuvae 作為 PPD 的一種治療選擇，並準備與她們的 HCP 就 Zurzuvae 進行有意義的討論。 HCP 將成為這一計劃中的全渠道方法的核心焦點，因為他們最終將直接負責做出開 Zurzuvae 治療產後抑鬱症女性的決定。我們相信，對於患有 PPD 的女性來說，早期積極的臨床經驗和可及性對於建立信心並加速 Zurzuvae 在該適應症中的採用至關重要。

HCP experience with Zurzuvae and treating women with PPD will be instrumental to update. We plan to have initiatives at launch in support of this. First, a full course therapy sample program that will distribute a 14-day short course of therapy to appropriate HCPs to trial Zurzuvae in the treatment of women with PPD. We believe this targeted early experience program will be critical to enabling rapid clinical experience with Zurzuvae that will ultimately drive long-term uptake in this PPD population.

HCP 在 Zurzuvae 和治療產後抑鬱症女性方面的經驗將有助於更新。我們計劃在啟動時採取舉措來支持這一點。首先，一個完整療程的治療樣本計劃，將向適當的 HCP 分發 14 天的短期療程，以試驗 Zurzuvae 治療患有 PPD 的女性。我們相信，這一有針對性的早期體驗計劃對於實現 Zurzuvae 的快速臨床體驗至關重要，最終將推動 PPD 人群的長期採用。

The second planned initiative is intended to help enable our goal that every woman with PPD whose prescribed Zurzuvae can access it, regardless of their financial circumstances. We plan to facilitate this effort through patient access programs at launch including co-pay assistance for eligible women with PPD, who are commercially insured. We intend to discuss our planned commercial strategy, these initiatives and other planned support for women with PPD closer to the time of launch. We are collaborating across the ecosystem with payers, health care providers, patient advocates and policymakers with the goal of providing a model for care that works in the best interest of patients to PPD.

第二個計劃舉措旨在幫助實現我們的目標，即每位患有 PPD 的女性，無論其經濟狀況如何，都可以使用 Zurzuvae 藥物。我們計劃通過啟動時的患者准入計劃來促進這一努力，包括為符合條件的患有 PPD 且有商業保險的女性提供共同支付援助。我們打算在臨近發佈時討論我們計劃的商業戰略、這些舉措以及其他計劃為患有產後抑鬱症的女性提供的支持。我們正在整個生態系統中與付款人、醫療保健提供者、患者權益倡導者和政策制定者合作，目標是提供一種符合 PPD 患者最大利益的護理模式。

In every state, there is a call to action to prioritize expanding and increasing access to treatment for maternal mental health. There is a need for solutions to address the significant gaps in care. As a new standard of care for women with PPD and a harbinger for change, Zurzuvae could improve outcomes for these patients, potentially lessen the overall burden and costs on society and more importantly, support these mothers and their intent to help them thrive. We believe that a combination of these efforts will help build a positive experience with Zurzuvae both for women with PPD and HCPs who treat them.

每個州都呼籲採取行動，優先擴大和增加孕產婦心理健康治療的機會。需要找到解決方案來解決護理方面的重大差距。作為產後抑鬱症女性的新護理標準和變革的預兆，Zurzuvae 可以改善這些患者的治療結果，有可能減輕社會的總體負擔和成本，更重要的是，支持這些母親及其幫助她們茁壯成長的意圖。我們相信，這些努力的結合將有助於為患有 PPD 的女性和治療她們的 HCP 建立積極的 Zurzuvae 體驗。

Finally, let's turn to market access. While it's too early to talk about price, here's how we're thinking about it. We plan to implement a PPD access strategy that recognizes the unmet need considerable economic burden and a novel clinical profile of Zurzuvae. We will continue to work with payers with the goal of favorable access and identify ways we might partner, including the potential role of value-based agreements. We have had numerous permitted engagements with payers in the month leading up to PDUFA, and payers recognize the significant unmet need for new treatment options in PPD and have been enthusiastic about the clinical profile of Zurzuvae in this indication.

最後，讓我們談談市場准入。雖然現在談論價格還為時過早，但我們對此的看法如下。我們計劃實施 PPD 准入策略，該策略認識到未滿足的需求相當大的經濟負擔和 Zurzuvae 的新穎臨床特徵。我們將繼續與付款人合作，以提供有利的准入機會，並確定我們可能合作的方式，包括基於價值的協議的潛在作用。在 PDUFA 發布之前的一個月裡，我們與付款人進行了多次獲准的接觸，付款人認識到 PPD 新治療方案的巨大需求未得到滿足，並且對 Zurzuvae 在該適應症中的臨床概況充滿熱情。

As we said, our goal is that every woman with PPD who is prescribed Zurzuvae can access it regardless of financial circumstances. As part of our final preparation, Sage and Biogen are currently working to determine adjustments to our thinking on price given the PPD label. We plan to provide more clarity on our overall thinking closer to product launch. What we can say now is that approximately 55% of U.S. births are covered by commercial insurance and our planned patient access approach for women with PPD were commercially insured as the goal of enabling a vast majority of these women have access to Zurzuvae with minimal out-of-pocket-costs. The remaining birds received covers through Medicaid, which requires little or no financial responsibility for the patient. We expect decisions by payers is to cover Zurzuvae the treatment for women with PPD to be made in the months following DEA scheduling.

正如我們所說，我們的目標是每位患有 PPD 並服用 Zurzuvae 處方的女性都可以使用該藥物，無論經濟狀況如何。作為我們最後準備工作的一部分，Sage 和 Biogen 目前正在努力調整我們對 PPD 標籤的價格思考。我們計劃在產品發布前更清晰地闡述我們的整體思路。我們現在可以說的是，大約 55% 的美國新生兒享受商業保險，我們計劃為患有 PPD 的女性患者提供商業保險，目標是讓絕大多數女性能夠以最少的支出獲得 Zurzuvae 服務。自付費用。其餘的鳥通過醫療補助獲得保險，這幾乎不需要患者承擔任何經濟責任。我們預計付款人將在 DEA 安排後的幾個月內決定為 Zurzuvae 支付 PPD 女性的治療費用。

We are prepared and eager to implement this launch strategy that we believe has the potential to maximize the impact of Zurzuvae in the treatment of women with PPD by aligning with each of our stakeholders. Through our planned commercialization efforts, we expect to rapidly reach both women with PPD and the HCPs to treat them. Finally, our goal is to enable a favorable access environment so that women with PPD who are prescribed Zurzuvae are able to get it both rapidly and affordably. We feel this urgency because women with PPD are waiting.

我們已準備好並渴望實施這一啟動戰略，我們相信，通過與我們的每個利益相關者保持一致，該戰略有可能最大限度地發揮 Zurzuvae 在治療產後抑鬱症女性方面的影響。通過我們計劃的商業化努力，我們期望能夠迅速接觸到患有產後抑鬱症的女性並讓 HCP 為她們提供治療。最後，我們的目標是創造一個有利的獲取環境，使服用 Zurzuvae 處方的產後抑鬱症女性能夠快速且經濟地獲得該藥。我們感到這種緊迫感是因為患有產後抑鬱症的女性正在等待。

I'll now turn it over to Kimi to provide a financial update. Kimi?

我現在將其轉交給 Kimi，以提供最新的財務信息。基米？

Thanks, Chris, and good morning, everyone. I want to share my excitement for this new chapter of opportunity and hope for women with PPD. We're energized to push forward and help so many of these women. And as Barry noted earlier, we are reviewing the feedback from the FDA and the CRL for MDD and evaluating next steps.

謝謝克里斯，大家早上好。我想與大家分享我對產後抑鬱症女性的機遇和希望新篇章的興奮之情。我們充滿活力地推動並幫助這些女性中的許多人。正如 Barry 之前指出的，我們正在審查 FDA 和 CRL 針對 MDD 的反饋並評估後續步驟。

Given these recent developments, I'd like to briefly comment on what this update means for our financial position. We will continue to make smart, disciplined decisions as we work to balance cash on hand and revenue generation with our operating expenses. We believe we are well capitalized with $1 billion in cash as of June 30. And based upon our current estimates, we expect that our cash, cash equivalents and marketable securities, along with anticipated funding from ongoing collaboration and potential revenue will support operations into 2025.

鑑於最近的事態發展，我想簡要評論一下此更新對我們的財務狀況意味著什麼。我們將繼續做出明智、嚴格的決策，努力平衡手頭現金和創收與運營支出。我們相信，截至6 月30 日，我們的資本充足，擁有10 億美元現金。根據我們目前的估計，我們預計我們的現金、現金等價物和有價證券，以及來自持續合作和潛在收入的預期資金將支持2025 年的運營。

With that said, given the update relating to the CRL and MTD, we are refining our strategy. We plan to take action with the goal of extending our cash runway and are currently evaluating resource allocation, including pipeline prioritization and a workforce reorganization. As a result, we also anticipate operating expenses to decrease in 2024. As Barry said, we are working towards a successful launch in PPD and believe the changes we plan to make will enable us to be a stronger, leaner and a more focused company. We expect to provide greater detail and next steps before the end of the third quarter as our plans unfold.

儘管如此，鑑於 CRL 和 MTD 的更新，我們正在完善我們的策略。我們計劃採取行動，以擴大我們的現金跑道，目前正在評估資源分配，包括管道優先級和勞動力重組。因此，我們還預計 2024 年運營費用將減少。正如 Barry 所說，我們正在努力成功推出 PPD，並相信我們計劃進行的變革將使我們成為一家更強大、更精簡、更專注的公司。隨著計劃的展開，我們預計將在第三季度末之前提供更多細節和後續步驟。

Before I turn the call over to Ashley for Q&A., I want to reiterate our excitement around this monumental milestone for Sage. We look forward to the commercial availability of Zurzuvae later this year and will act with urgency to help enable women with PPD who are prescribed Zurzuvae to have access to it. Let me also add that I know there are many questions out there given the CRL and MDD. As we always have, we'll provide updates when we can.

在我將電話轉給 Ashley 進行問答之前，我想重申我們對 Sage 的這一里程碑式的興奮。我們期待 Zurzuvae 在今年晚些時候上市，並將緊急採取行動，幫助患有 PPD 且服用 Zurzuvae 的女性能夠獲得該藥。我還想補充一點，我知道 CRL 和 MDD 存在很多問題。一如既往，我們將盡可能提供更新。

With that, I'll turn the call over to Ashley.

這樣，我會將電話轉給阿什利。

Thanks, Kimi.

謝謝，基米。

(Operator Instructions)

（操作員說明）

Now I'll turn it over to the operator to handle Q&A. Operator?

現在我將把它交給接線員來處理問答。操作員？

(Operator Instructions)

（操作員說明）

We'll go first to Salveen Richter with Goldman Sachs.

我們首先請教高盛的 Salveen Richter。

Congratulations on the approval here in PPD. Maybe just to start here with the launch. You talked about the outreach effort with the prescribers. Could you just quantify the prescriber base for us and help us understand the targeted approach and also how a sampling program will work in the context of ensuring you're not soaking up all that initial demand?

恭喜 PPD 獲得批准。也許只是從這裡開始。您談到了與處方醫生的外展工作。您能否為我們量化處方者基礎，幫助我們了解有針對性的方法以及抽樣計劃如何在確保您不會吸收所有初始需求的情況下發揮作用？

Yes, Salveen, thanks for the congratulatory note. We're really excited about the approval of Zurzuvae in the treatment of women for PPD, and we're really looking forward to helping these women. We're excited about the opportunity and believe we have a strong business case with a right-sized organization at the right price, we've got many tailwinds that may help us in launching Zurzuvae for the treatment of women. As we noted, it's a big unmet need, about 0.5 million women in the U.S. experienced symptoms each year. The fact that this first and only oral treatment approved for women with PPD. And we believe health care providers are looking for a tool like this to solve their dilemma and what to do when they diagnose the mom with PPD. And we know that the payers, and I'll ask Chris to comment more about the sample program. .

是的，Salveen，謝謝您的賀信。我們對 Zurzuvae 獲得批准用於治療女性產後抑鬱症感到非常興奮，我們真的很期待幫助這些女性。我們對這個機會感到興奮，並相信我們擁有強大的商業案例，擁有規模合適、價格合適的組織，我們有許多順風車，可以幫助我們推出 Zurzuvae 來治療女性。正如我們所指出的，這是一個巨大的未滿足需求，美國每年約有 50 萬女性出現症狀。事實上，這是第一個也是唯一一個口服治療方法被批准用於患有產後抑鬱症的女性。我們相信醫療保健提供者正在尋找這樣的工具來解決他們的困境以及當他們診斷出母親患有產後抑鬱症時該怎麼辦。我們知道付款人，我會請 Chris 對示例程序進行更多評論。 。

We are looking forward to a new option for PPD. And certainly -- and we mentioned this in the script that every state and policies, they're implementing policies that we believe will enable access for women at PPD. We can't talk about yet our target numbers per se or the size of the sampling program, but maybe Chris can talk about the importance of the full course treatment and activating health care providers to see the results and with their own eyes.

我們期待 PPD 的新選擇。當然，我們在劇本中提到了這一點，每個州和政策都在實施我們相信將使女性能夠進入 PPD 的政策。我們還不能談論我們的目標數字本身或抽樣計劃的規模，但克里斯也許可以談論全程治療和激活醫療保健提供者親眼看到結果的重要性。

Yes. Thanks, Barry. So at launch, we're going to focus our field sales team, as I said in my opening remarks on high prescribing OB/GYN psychiatrists and PCPs. And as you noted, it's going to be really important for that group of physicians to have early experience with Zurzuvae and what that entails is giving them access to a 14-day full course therapy sample so that they have that experience to see the impact that Zurzuvae can have on women living with PPD in that practice.

是的。謝謝，巴里。因此，在啟動時，我們將重點關注我們的現場銷售團隊，正如我在開場白中談到高處方婦產科精神科醫生和 PCP 時所說的那樣。正如您所指出的，對於該組醫生來說，儘早獲得 Zurzuvae 的經驗非常重要，這需要讓他們獲得 14 天的全程治療樣本，以便他們有經驗來了解 Zurzuvae 的影響在這種做法中，Zurzuvae 可以對患有產後抑鬱症的女性產生影響。

Can I just follow up just quickly just to get a sense of quantification of that physician base that you're targeting initially? And just help us understand the flexibility you have on pricing and PPD?

我可以快速跟進，以了解您最初瞄準的醫生基礎的量化情況嗎？請幫助我們了解您在定價和 PPD 方面的靈活性？

Yes. So right now, we really can't talk about the kind of the size of the physician base. As you're well aware, we and our collaborators Biogen have been working wholeheartedly on preparing for a PPD and MDD launch. It has done a lot of work. Of course, we have PPD scenarios that played out, but now the work begins for our PPD focused launch. As we closer to launch, we'll come back out with specifics about how we're targeting it. As Chris said in his remarks, we're thinking big about the opportunity, but we're going to start in a very focused way and have clear metrics to scale with success. In terms of pricing, as I said, we think that with the right price and the right sized organization, we have a very strong business case, and we're setting about to do that work now.

是的。所以現在我們真的不能談論醫生基礎的規模。如您所知，我們和我們的合作夥伴 Biogen 一直在全心全意地為 PPD 和 MDD 的推出做準備。它已經做了很多工作。當然，我們已經完成了 PPD 場景，但現在我們開始以 PPD 為重點的發布工作。當我們接近發佈時，我們將詳細介紹我們的目標。正如克里斯在講話中所說，我們正在認真考慮這個機會，但我們將以非常專注的方式開始，並製定明確的衡量標準來衡量成功。在定價方面，正如我所說，我們認為，通過合適的價格和合適規模的組織，我們擁有非常強大的業務案例，我們現在就著手開展這項工作。

We'll go next to Ritu Baral with TD Cowen.

我們將與 TD Cowen 一起前往 Ritu Baral。

And I'd like to add my congratulations that the drug is available for PPD patients. I would like to focus a little bit on MDD, Barry. I know you can't talk too much about the interactions and the status. But could you go through at least what happened during the review? Any review issues that were discussed at the mid-cycle review that are now a focus of unresolved questions? And then what is your expectations of timing for a typing needing to reach clarity on what else is needed?

我還要祝賀該藥物可供產後抑鬱症患者使用。 Barry，我想稍微關註一下 MDD。我知道你不能過多談論互動和狀態。但您至少能回顧一下審核期間發生的事情嗎？中期審核中討論過的任何審核問題現在成為未解決問題的焦點？然後，您期望什麼時間進行打字，以明確還需要什麼？

Yes, Ritu, thank you for the congratulatory note. And as you asked, we'll focus on this MDD. So just to be clear, we're extremely disappointed for patients with MDD. We're more devastated that we're not able to help them right now. And actually, we do not agree with the FDA's view on Zurzuvae for MDD. Mental health crisis is having a devastating impact on our communities, as you know, and we're in desperate need of innovation. So if I back up we in accordance with FDA last year filed our NDA package, and we have started the roll in submission earlier in the year with some of the modules.

是的，Ritu，謝謝你的賀信。正如您所問的，我們將重點關注這個 MDD。需要明確的是，我們對重度抑鬱症患者感到非常失望。我們現在無法幫助他們，這讓我們更加沮喪。事實上，我們並不同意 FDA 對 Zurzuvae 治療 MDD 的看法。如您所知，心理健康危機正在對我們的社區產生毀滅性影響，我們迫切需要創新。因此，如果我支持的話，我們去年根據 FDA 提交了 NDA 包，並且我們已經在今年早些時候開始提交一些模塊。

In the clinical section, we had what we believe was 6 of 7 placebo-controlled, positive clinical studies to support of that package, which we believe was supportive of both PPD and MDD. We learned late in the review cycle about FDA's view on approvability for MDD. And as we noted, we received the CRL late on Friday. So the review they did filing pack involves an analysis of the submitted information. And we really can't speculate on the FDA's thinking or decision making. We can simply reflect on what they put in the CRL, which again, we got late Friday. So we're reviewing the feedback and evaluating the next steps and we're excited to launch Zurzuvae in PPD as we work with our collaborative Biogen in understanding what our next steps with FDA on MDD are.

在臨床部分，我們認為 7 項安慰劑對照、陽性臨床研究中有 6 項支持該方案，我們認為該方案支持 PPD 和 MDD。我們在審查週期後期了解到 FDA 對 MDD 批准性的看法。正如我們所指出的，我們在周五晚些時候收到了 CRL。因此，他們對歸檔包進行的審查涉及對提交的信息進行分析。我們確實無法推測 FDA 的想法或決策。我們可以簡單地反思一下他們在 CRL 中放入的內容，我們再次在周五晚些時候收到了 CRL。因此，我們正在審查反饋並評估後續步驟，我們很高興在 PPD 中推出 Zurzuvae，因為我們與合作的百健 (Biogen) 合作，了解我們與 FDA 就 MDD 採取的下一步措施。

Do you anticipate interaction even before a Type A meetings?

您是否在 A 類會議之前就預計會有互動？

I really can't say anything else you took except that we advise and reviewing the feedback and evaluating the next steps. We've got the right team on it.

除了我們提供建議、審查反饋並評估後續步驟之外，我真的不能說您採取的任何其他措施。我們有合適的團隊。

We'll go next to Paul Matteis with Stifel.

我們將和斯蒂菲爾一起去保羅·馬蒂斯旁邊。

I guess without being able to talk about the price, which was sort of my first question, I wanted to ask a little bit about the label because I think there are a few things on there that surprised investors that might have read through onto the pipeline. One was commentary around abuse. Another was a commentary on a prior dog study, which seems like it might have been an impediment to chronic administration. And then also restrictions around driving. How do -- are those surprising to you that they were on the label, one? And two, do those put into question the profile of SAGE-324, which has been given chronically and has the same mechanism of action?

我想，在無法談論價格的情況下（這是我的第一個問題），我想詢問一些有關標籤的信息，因為我認為其中有一些東西讓投資者感到驚訝，他們可能已經閱讀了管道。其中之一是關於虐待的評論。另一個是對先前的狗研究的評論，這似乎可能是長期給藥的障礙。然後還有駕駛方面的限制。標籤上出現的那些東西讓你感到驚訝嗎？第二，那些人是否對長期服用且具有相同作用機制的 SAGE-324 的概況提出了質疑？

Paul, thank you for the question. Let me just start out and then I'll turn it to Laura to talk about some of the specifics. So we believe that the label that's provided for us for the treatment of PPD is a fine label. It's a label that is instructive. It's protective and it's instructive for health care providers and their patients. Certainly a label that allows us to sell Zurzuvae for the treatment of PPD for women and a label we can move forward. So nothing in the label is surprising per se or problematic. But maybe Laura can talk more about that.

保羅，謝謝你的提問。讓我先開始，然後我將轉給勞拉討論一些具體細節。因此，我們相信為我們提供的用於治療 PPD 的標籤是一個很好的標籤。這是一個有指導意義的標籤。它具有保護作用，對醫療保健提供者及其患者俱有指導意義。當然，這是一個允許我們銷售用於治療女性產後抑鬱症的 Zurzuvae 的標籤，也是一個我們可以繼續前進的標籤。因此，標籤中的內容本身並不令人驚訝或有問題。但也許勞拉可以多談談這一點。

Sure. Thanks for the question, Paul. I'll start first with your question related to driving. So as you see in the label, there is a box warning for driving that instructs prescribers to counsel their patients not to drive or are engaged in other potentially hazardous activities into at least 12 hours after each dose of Zurzuvae for the duration of the 14-day treatment course. This recommendation was based on data that's included at the end of the label that summarizes the results of 2 driving studies that Sage conducted. I can summarize briefly the results from the 50-milligram dose because that's the most relevant since it's the clinical dose. At the 50-milligram dose, Zurzuvae caused driving impairment after 1 day of dosing and after 7 days of dosing, which was the last time point measured. The label contains very clear instructions for patients. And from our perspective, patient safety has to be top of mind. And it's good that these clear instructions are in the label because it will enable physicians to have good discussions with our patients about the benefit risk profile of Zurzuvae.

當然。謝謝你的提問，保羅。我首先從你關於駕駛的問題開始。因此，正如您在標籤中看到的，有一個關於駕駛的方框警告，指示處方醫生建議患者在每次服用 Zurzuvae 後 14 小時內至少 12 小時內不要開車或從事其他潛在危險活動。日治療療程。此建議基於標籤末尾包含的數據，該數據總結了 Sage 進行的兩項駕駛研究的結果。我可以簡要總結 50 毫克劑量的結果，因為這是最相關的，因為它是臨床劑量。在 50 毫克劑量下，Zurzuvae 在給藥 1 天和給藥 7 天（最後測量的時間點）後引起駕駛障礙。標籤包含非常清晰的患者說明。從我們的角度來看，患者的安全必須放在首位。標籤中包含這些明確的說明是件好事，因為它將使醫生能夠與我們的患者就 Zurzuvae 的獲益風險狀況進行良好的討論。

With regard to abuse liability. This is not unexpected for a drug with a mechanism of action like Zurzuvae. It -- as you can see from what's in the label, there are results from these liability studies that show that Zurzuvae at 30 and 60 milligrams has less abuse potential than the control, which was a benzodiazepine. But at the 90-milligram dose was approximately equivalent in a best potential to vetoes. Based on this, we expect that Zurzuvae will be DEA-scheduled likely Schedule IV like similar drugs like benzodiazepines. The prescribers who will be prescribing medications for PPD are experienced in prescribing Schedule IV agents, and we don't expect this to be an impediment to use.

關於濫用責任。對於 Zurzuvae 這樣具有作用機制的藥物來說，這並不意外。正如您從標籤上看到的那樣，這些責任研究的結果表明，30 毫克和 60 毫克的 Zurzuvae 的濫用可能性比對照（苯二氮卓類藥物）要低。但 90 毫克的劑量大約相當於否決的最佳潛力。基於此，我們預計 Zurzuvae 將像苯二氮卓類藥物一樣被 DEA 列入附表 IV。為 PPD 開藥的處方醫生在開附表 IV 藥物方面經驗豐富，我們預計這不會成為使用的障礙。

Yes. Let me wrap back with your question about the rest of the pipeline or GABA PAM. So as we stated, we intend to complete the KINETIC 2 study for SAGE-324 at the end of the year. Every new chemical entity has it's unique entity, and it's hard to understand if there are any read-throughs in this label or not, Typically, labeling occurs on the basis of data for each individual product. So that's what we can say right now.

是的。讓我總結一下您關於管道其餘部分或 GABA PAM 的問題。正如我們所說，我們打算在今年年底完成 SAGE-324 的 KINETIC 2 研究。每個新的化學實體都有其獨特的實體，很難理解該標籤中是否有任何通讀內容。通常，標籤是根據每個產品的數據進行的。這就是我們現在可以說的。

We'll go next to Yasmeen Rahimi with Piper Sandler.

接下來我們將與 Piper Sandler 一起前往 Yasmeen Rahimi。

I know there's a lot that you can tell us about MDD, but could you maybe comment on what are some of the requirements that you would want to maybe not go through in case like if there's multiple additional studies required. Is that something that you would want to do I guess what we're trying to figure out is like your commitment to really move this forward in getting this approved? And then the second question for me is just sort of helping us understand how many courses or (inaudible) would be used in patients with PPD, whether you would recommend 1 or 2? And if you could maybe help us understand sort of the use of this product within 1 year? And I'll jump back into the queue.

我知道您可以告訴我們很多關於 MDD 的內容，但是您能否評論一下您可能不想滿足的一些要求，以防需要進行多項額外研究。這是您想要做的事情嗎？我想我們正在努力弄清楚您是否承諾真正推動這項工作獲得批准？對我來說第二個問題只是幫助我們了解 PPD 患者將使用多少療程或（聽不清），您是否會推薦 1 個或 2 個療程？您能否在一年內幫助我們了解該產品的使用情況？我會跳回到隊列中。

Yes, thanks for the question. Let me start with PPD, and I'll circle back. So what we saw in our clinical studies on the profile of Zurzuvae was these women that took Zurzuvae in the evening with a meal, saw rapid response as early as 3 days, continued response up to day 15, that's clinically relevant and statistically different than placebo. And that effect has lasted out to day 45 with statistical significance to clinical relevant. So with that profile, we envision that a mom would take 1 14-day course in the course of the year because the trigger event was getting pregnant or having that baby.

是的，謝謝你的提問。讓我從 PPD 開始，然後我會再回過頭來。因此，我們在關於 Zurzuvae 的臨床研究中看到，這些女性在晚上隨餐服用 Zurzuvae，最早 3 天就出現快速反應，持續反應持續到第 15 天，這與安慰劑具有臨床相關性和統計學差異。這種效果一直持續到第 45 天，具有與臨床相關的統計顯著性。因此，根據該資料，我們預計媽媽會在一年中參加 1 個為期 14 天的課程，因為觸發事件是懷孕或生孩子。

So I guess the short answer is one. Now looping back to this year. I'll repeat it, and we're extremely disappointed for patients, and we don't agree with the FDA's view. They issued the CRL related to NDA for zuranolone for the treatment of adults with MDD and looking at which is, the application did not provide substantial evidence of effectiveness to support the approval of zuranolone, the treatment of MDD and that additional study or studies are needed. We're reviewing the feedback and evaluating next steps, and we really can't comment further other than that.

所以我想簡短的答案是一。現在回溯到今年。我再說一遍，我們對患者感到非常失望，我們不同意 FDA 的觀點。他們發布了與 zuranolone 用於治療成人 MDD 的 NDA 相關的 CRL，並研究了該申請沒有提供實質性的有效性證據來支持 zuranolone 的批准、MDD 的治療，並且需要進行額外的研究。我們正在審查反饋並評估後續步驟，除此之外我們確實無法發表進一步評論。

We'll go next to Anupam Rama with JPMorgan.

接下來我們將與摩根大通一起去阿努帕姆·拉瑪 (Anupam Rama)。

And congrats on the PPD approval here. Barry, you've mentioned a couple of times the right price in PPD. Maybe you could give us a little bit of color on the book end to kind of consider, whether it's ZULRESSO or other products. And what are the key considerations to getting to that right price?

在此恭喜 PPD 獲得批准。 Barry，您已經多次提到 PPD 中的正確價格。也許你可以在書尾給我們一點顏色來考慮，無論是 ZULRESSO 還是其他產品。獲得合適價格的關鍵考慮因素是什麼？

Yes, Anupam, I'll start and I'll turn it over to Chris up and again, thank you very much for the congratulatory note. Again, we're really excited to help women suffering from PPD. Just to be clear, we can't comment on price or bookends right now. As I mentioned, we did a significant amount of approved pre-commercial payer introduction with the plan to launch MDD and PPD. We had significant amount of conversations about what the value-based agreements would look like. And frankly, we're prepared for PPD, MDD launch with payers to move forward in contracting. We now have to go back, given the results from Friday and the fact that we got the CRL Friday and reengaged payers, but we have some basis to do that. Maybe Chris will talk more about that.

是的，阿努帕姆，我會開始，然後我會把它交給克里斯，非常感謝你的賀信。再次，我們非常高興能夠幫助患有產後抑鬱症的女性。需要明確的是，我們現在無法評論價格或書立。正如我所提到的，我們通過推出 MDD 和 PPD 的計劃進行了大量經批准的預商業付款人介紹。我們就基於價值的協議的內容進行了大量討論。坦率地說，我們已準備好與付款人一起推出 PPD、MDD，以推進簽約工作。考慮到週五的結果以及我們週五收到 CRL 並重新與付款人接洽的事實，我們現在必須回去，但我們有一些基礎可以做到這一點。也許克里斯會更多地談論這一點。

Yes, sure. Thanks, Barry. We've historically said to be truly transformational. We must be accessible with Zurzuvae. We're committed to the goal of rapid and equitable access to Zurzuvae for the hundreds of thousands of women who live with PPD. When we think about the approval of Zurzuvae and the treatment of women with PPD in the absence of an MDD indication, we'll need to consider the size of the patient population, obviously, the strength of the clinical data, including statistical significance at all time points and the clinical potential of Zurzuvae to address significant unmet need for new innovative options in the treatment of postpartum depression. These factors ultimately are what will influence our target wholesale acquisition cost. However, regardless of the WACC, our goal is that every woman, as I said, with PPD is prescribed Zurzuvae access it regardless of the financial circumstances.

是的，當然。謝謝，巴里。我們歷史上曾說過，這是真正的變革。我們必須與 Zurzuvae 保持聯繫。我們致力於實現為數十萬患有產後抑鬱症的女性快速、公平地獲得 Zurzuvae 的目標。當我們考慮批准 Zurzuvae 以及在沒有 MDD 適應症的情況下治療 PPD 女性時，我們需要考慮患者群體的規模，顯然，臨床數據的強度，包括統計顯著性Zurzuvae 的時間點和臨床潛力，可滿足產後抑鬱症治療新創新方案的重大未滿足需求。這些因素最終將影響我們的目標批發採購成本。然而，無論 WACC 如何，我們的目標是，正如我所說，每位患有 PPD 的女性都可以使用 Zurzuvae，無論財務狀況如何。

We'll go next to Tazeen Ahmad with Bank of America.

接下來我們將與美國銀行聯繫 Tazeen Ahmad。

I just wanted to clarify, did FDA asked you to submit both applications for PPD and MDD at the same time? Or was it the preference or was the safest preference to do it together? Also, you mentioned that the comments from FDA about the concerns around MDD didn't comment so late in the review cycle. Would there have been any opportunity to have an AdCom when they brought up the concerns in order to be able to flush it out better?

我只是想澄清一下，FDA是否要求你們同時提交PPD和MDD申請？或者這是一起做的偏好還是最安全的偏好？另外，您提到 FDA 對 MDD 擔憂的評論在審查週期的後期並未發表評論。當他們提出問題時，是否有機會讓 AdCom 更好地解決問題？

Yes, Tazeen, several different questions in there. So if I go back historically 2.5, 3 years. We did, as Sage, announced that we were going to file the NDA for both PPD and MDD. You might remember, at some point, it looks like our PPD study was delayed. And at that point, we went out and said, we're going to file MDD first and PPD after that. And then as the PPD study caught up, we announced that we were going to start a rolling submission and then launch both PPD and MDD at the end of the year. All of that was done in concordance with the FDA. In terms of what I can say about the interactions, as you noted, we filed the NDA. The FDA in February, we announced the FDA gave us a PDUFA date, August 5 and prior year review. And the FDA told us there was no AdCom required, which at the time, obviously, we took a good positive sum. And then just to add to that, we found out late in the review cycle about the FDA's view on the approvability of MDD. Other than that, I can't say much more.

是的，塔津，其中有幾個不同的問題。所以如果我回到歷史 2.5、3 年。我們確實像 Sage 一樣宣布我們將為 PPD 和 MDD 提交 NDA。您可能還記得，在某個時候，我們的 PPD 研究似乎被推遲了。那時，我們出去說，我們將首先提交 MDD，然後提交 PPD。然後，隨著 PPD 研究的進展，我們宣布將開始滾動提交，然後在年底同時推出 PPD 和 MDD。所有這些都是按照 FDA 的規定進行的。就我可以說的互動而言，正如您所指出的，我們提交了保密協議。 FDA 在 2 月份宣布 FDA 給了我們 PDUFA 日期，8 月 5 日和上一年的審查。 FDA 告訴我們不需要 AdCom，顯然，當時我們得到了一筆可觀的正金額。除此之外，我們在審查週期後期發現了 FDA 對 MDD 批准性的看法。除此之外，我不能說更多。

We'll go next to Brian Abrahams with RBC Capital Markets.

接下來我們將採訪加拿大皇家銀行資本市場部的布萊恩·亞伯拉罕斯 (Brian Abrahams)。

My congratulations as well on the approval in PPD. Maybe a question on MDD. Do you see a potential for a more narrow or refined indication like the treatment of an acute depressive episode or adjunctive treatment? Is this something that was ever discussed with the agency or potentially on the table? And if this is a possibility, do you think additional studies would be required to support that or not?

我也祝賀 PPD 獲得批准。也許是關於 MDD 的問題。您是否認為有可能進行更狹窄或更精細的適應症，例如治療急性抑鬱發作或輔助治療？這是否曾經與該機構討論過或可能擺在桌面上？如果這是可能的，您認為是否需要更多的研究來支持這一點？

Brian, thank you very much for a very insightful question. I guess what we can say at this time is we're extremely disappointed for patients, whether it's for the treatment of MDD or different indications, and we don't agree with the FDA's view. We are evaluating the CRL. And as soon as we can provide more clarity, we will on what the next steps are. We really do believe that zuranolone should be available to treat patients with MDD, but we've got to get there. And until we're there, we'll be solely focused in marketing for Zurzuvae to treat women with PPD.

布萊恩，非常感謝你提出了一個非常有見地的問題。我想我們此時能說的是我們對患者感到極其失望，無論是對於MDD的治療還是不同的適應症，我們不同意FDA的觀點。我們正在評估 CRL。一旦我們能提供更清晰的信息，我們就會決定接下來的步驟。我們確實相信 zuranolone 應該可用於治療 MDD 患者，但我們必須實現這一目標。在此之前，我們將專注於 Zurzuvae 的營銷，以治療患有產後抑鬱症的女性。

We'll go next to Jay Olson with Oppenheimer.

接下來我們將和奧本海默一起去傑·奧爾森。

Congrats on the PPD approval. We have a financial question. Since you'll be eligible for a $225 million milestone from Biogen and you'll also experience potentially significant cost savings in the near term without an MDD launch. Are you in a financial position to accelerate the development of SAGE-718 and do you plan to continue that development independently or potentially seek a partnership?

恭喜 PPD 批准。我們有一個財務問題。由於您將有資格獲得 Biogen 提供的 2.25 億美元里程碑資金，並且您還將在短期內體驗到潛在的顯著成本節省，而無需啟動 MDD。您是否有能力加速 SAGE-718 的開發，並且您計劃繼續獨立開發還是可能尋求合作夥伴關係？

Yes, Jay, first of all, thanks for the congratulatory note. I'll let Kimi talk about the milestone and some of our financial thinking. But in terms of SAGE-718, we continue to be really excited by developing SAGE-718 or wholly owned an NDA. PAM, the data we've seen to date is exciting in terms of cognitive improvement that we saw in Huntington's, Parkinson's and Alzheimer's, albeit probe studies and open-label studies. As you're well aware, we have a significant #5 well-controlled studies underway right now, several in Huntington's and then Parkinson's and Alzheimer's. Those should set us up for a very [de] rich year next year in terms of SAGE-718, and as we've commented before, we believe that the Huntington's package is set up in a way that if we see robust data and given that it's an orphan indication, we do believe there's some regulatory flexibility, and we'll pursue that a flexible approach.

是的，傑伊，首先感謝您的賀信。我會讓 Kimi 談談這個里程碑和我們的一些財務想法。但就 SAGE-718 而言，我們仍然對開發 SAGE-718 或全資擁有 NDA 感到非常興奮。 PAM，迄今為止，我們在亨廷頓舞蹈症、帕金森舞蹈症和阿爾茨海默病中看到的認知改善方面的數據令人興奮，儘管是探索性研究和開放標籤研究。如您所知，我們目前正在進行一項重要的#5 良好對照研究，其中幾項針對亨廷頓氏症，然後針對帕金森氏症和阿爾茨海默氏症。就 SAGE-718 而言，這些應該為我們明年帶來非常豐富的一年，正如我們之前評論的那樣，我們相信亨廷頓包的建立方式是，如果我們看到可靠的數據並給定雖然這是一個孤兒適應症，但我們確實相信存在一定的監管靈活性，我們將採取靈活的方法。

Whether it accelerates or not is another question. That's a matter of clinical studies enrolling in -- and how rapid they enroll. But we have said previously that we're excited at Sage alone to launch SAGE-718 in Huntington's given the orphan nature and the sort of smaller capital footprint that needs, we're excited to do that. Kimi, can you talk about kind of milestones and other financial guidance?

是否加速是另一個問題。這是臨床研究的註冊情況以及註冊速度的問題。但我們之前曾說過，考慮到 SAGE-718 的孤兒性質和所需的較小資本足跡，我們很高興 Sage 獨自在亨廷頓推出 SAGE-718，我們很高興這樣做。 Kimi，您能談談里程碑和其他財務指導嗎？

Sure. It's a great question. So just a reminder, earlier I talked about that based on our current estimates, we expect that the cash on hand anticipated funding from collaborations and potential revenue will support our operations into 2025. And we also mentioned that we have the potential to earn a milestone payment of $75 million from Biogen related to the first commercial sale of Zurzuvae for the treatment of PPD. But to be clear, based on the receipt of the CRL on Friday evening, we are looking forward to and plan to refine our strategy and spend. So that's going to really include an evaluation of our resource allocation. We'll be looking at the pipeline. We'll be looking at a workforce reorganization and that's all with the goal of extending our cash runway. We expect our evaluation of our resource allocation will incorporate the feedback from the FDA that we have in that quick time. So we expect that we'll be able to update all of you by the end of the third quarter, and we'll certainly talk to you once we have it on (inaudible).

當然。這是一個很好的問題。提醒一下，之前我談到，根據我們目前的估計，我們預計手頭的現金、來自合作的預期資金和潛在收入將支持我們的運營到 2025 年。我們還提到，我們有潛力實現一個里程碑Biogen 支付了7500 萬美元，用於治療PPD 的Zurzuvae 的首次商業銷售。但需要明確的是，根據周五晚上收到的 CRL，我們期待併計劃完善我們的策略和支出。因此，這將真正包括對我們的資源分配的評估。我們將關注管道。我們將考慮進行勞動力重組，這一切都是為了擴大我們的現金跑道。我們預計我們對資源分配的評估將納入 FDA 的反饋意見。因此，我們希望能夠在第三季度末之前向大家通報最新情況，並且一旦我們啟動（聽不清），我們肯定會與你們交談。

And Jay, just some additional color since you mentioned it, as Chris Benecchi said, we're thinking big about the opportunity to help on PPD is 0.5 million women, but it certainly starts with a very focused footprint in terms of commercialization, omnichannel. And then we'll have markers that scale that with success, but we're certainly not going to overscale the launch for PPD.

Jay，既然你提到了這一點，就補充一點，正如Chris Benecchi 所說，我們正在認真考慮為50 萬女性提供PPD 幫助的機會，但它肯定是從商業化、全渠道方面非常集中的足跡開始的。然後我們將有成功擴展該規模的標記，但我們肯定不會過度擴展 PPD 的發布。

We'll go next to Sumant Kulkarni with Canaccord.

接下來我們將與 Canaccord 一起前往 Sumant Kulkarni。

How collaborative with Biogen do you expect the Zurzuvae launch to be? And do you expect to announce pricing on PPD prior to interacting with the FDA on MDD or after?

您預計 Zurzuvae 的推出與百健 (Biogen) 的合作程度如何？您希望在與 FDA 就 MDD 進行互動之前還是之後宣布 PPD 的定價？

Sumant, thank you for those questions. So in terms of Biogen, we at Biogen have been working extraordinarily collaboratively preparing for the potential of an MDD and PPD launch if approved. We -- and they got the label and the approval for PPD Friday night and the CRL for Friday night. And then as you saw, we together issued a joint press release a couple of hours later, announcing that we plan to launch Zurzuvae for PPD and have that launch available in the fourth quarter of this year and shortly after the DEA scheduling, which we -- it takes approximately 90 days. So that was a joint collaborative press release. Now with the approval of PPD in front of us and the CRL, we now turn our attention to working towards the appropriate launch of PPD in response to CRL and plan on doing that, as I said together. In terms of price timing, as we get closer to launch, we will be talking about our access strategy as well as some of the other aspects of our commercialization because that will be closer to launch.

蘇曼特，謝謝你提出這些問題。因此，就 Biogen 而言，我們 Biogen 一直在密切合作，為 MDD 和 PPD 上市的潛力（如果獲得批准）做準備。我們 - 他們獲得了周五晚上的 PPD 和周五晚上的 CRL 的標籤和批准。然後，正如您所看到的，幾個小時後，我們一起發布了一份聯合新聞稿，宣布我們計劃為 PPD 推出 Zurzuvae，並在今年第四季度和 DEA 安排後不久推出，我們 - - 大約需要90 天。這是一份聯合協作新聞稿。現在，隨著我們面前的 PPD 和 CRL 獲得批准，我們現在將注意力轉向努力適當啟動 PPD，以響應 CRL 併計劃這樣做，正如我一起所說的那樣。就價格時機而言，隨著我們越來越接近發布，我們將討論我們的訪問策略以及我們商業化的一些其他方面，因為這將更接近發布。

We'll go next to Laura Chico with Wedbush Securities.

接下來我們將討論韋德布什證券公司的勞拉·奇科 (Laura Chico)。

I guess just kind of following up on that. I don't know if there's any additional color you can provide on kind of the remainder of '23 in terms of the acceleration on SG&A in terms of PPD launch preparation. And I guess I'm trying to understand kind of the allocation of resources also between you and Biogen. And I guess I'm just trying to understand more broadly, Barry, you had some good comments with respect to how those 2 partners have interacted over the weekend here. But what is Biogen's commitment to a PPD launch that would just seem a little bit of a difference than if MDD was involved? Not sure if you can add any color there.

我想只是跟進一下。我不知道您是否可以就 23 年剩餘時間在 PPD 啟動準備方面加速 SG&A 方面提供任何其他信息。我想我正在嘗試了解您和百健（Biogen）之間的資源分配情況。我想我只是想更廣泛地了解，巴里，你對這兩個合作夥伴週末在這裡的互動方式提出了一些很好的評論。但是百健（Biogen）對 PPD 推出的承諾是什麼？這似乎與 MDD 的參與略有不同？不確定是否可以在那裡添加任何顏色。

Yes, Laura, thanks for all those questions and one question. So I guess what I can say is that, look, I can point to the joint press release where we and Biogen committed that we have Zurzuvae to available for PPD in the fourth quarter, shortly after DA scheduling. I can't really talk more about the allocation of resource yet. As I said, we worked really hard and preparing for the potential of an MDD and PPD launch if approved and had that clearly well mapped. With the news on Friday, the approval of PPD, the CRL for MDD, we're now turning our attention to do the work necessary for what the launch of PPD looks like. And as we get closer to launch, we can talk more about what that looks like. In terms of SG&A or other builds, as Kimi said, we anticipate looking at all resources as well as our workforce. And as I've commented earlier, we do believe that even in PPD with the right price and the right size of organization, we've got a really strong business case.

是的，勞拉，感謝所有這些問題和一個問題。所以我想我能說的是，看，我可以指出我們和百健（Biogen）的聯合新聞稿，我們承諾在第四季度（即 DA 安排後不久）將 Zurzuvae 用於 PPD。我還不能真正談論資源分配。正如我所說，我們非常努力地工作，並為 MDD 和 PPD 啟動的潛力做好準備（如果獲得批准並有清晰的規劃）。隨著周五消息的發布，PPD（MDD 的 CRL）獲得批准，我們現在將注意力轉向開展 PPD 啟動所需的工作。隨著我們越來越接近發布，我們可以更多地討論它的樣子。正如 Kimi 所說，在 SG&A 或其他建設方面，我們預計會考慮所有資源以及我們的員工隊伍。正如我之前評論的那樣，我們確實相信，即使在 PPD 中具有合適的價格和合適的組織規模，我們也擁有非常強大的業務案例。

We'll go to our next caller from Ami Fadia with Needham & Company.

我們將接聽來自 Ami Fadia 的 Needham & Company 的下一位來電者。

This is Eason Lee on for Ami. Maybe just kind of on -- regarding kind of Biogen again. I mean -- just I think just kind of the recent comments on earnings and the acquisition they announced it just -- I think it's created kind of a perception by some that maybe there could be less committed to MDD. So I kind of hear you on the joint press release and stuff. But maybe like how much -- I mean, can you give us a sense just like how much commitment do you think Biogen is on surround alone and MDD? And then with regards to a potential kind of resubmission effort and kind of the effort that would be required for that, like, I mean, what role would you anticipate Biogen kind of playing in that?

這是 Ami 的 Eason Lee。也許只是再次關於百健（Biogen）。我的意思是——我認為最近對他們剛剛宣布的收益和收購的評論——我認為這讓一些人產生了一種看法，即可能會減少對 MDD 的投入。所以我聽到了你關於聯合新聞稿之類的內容。但也許有多少——我的意思是，你能給我們一個感覺，就像你認為 Biogen 在環繞聲和 MDD 方面有多少承諾？然後，關於潛在的重新提交工作以及為此需要的工作，我的意思是，您預計百健（Biogen）在其中扮演什麼角色？

Yes, Eason, thank you for the question. I really can't say anything more than we've already said. We're preparing for the launch of the Zurzuvae and PPD and examining the CRL. We're reviewing the feedback and evaluating the next steps. I can't really comment more than that.

是的，伊森，謝謝你的提問。除了我們已經說過的話，我真的不能再說什麼了。我們正在準備推出 Zurzuvae 和 PPD 並審查 CRL。我們正在審查反饋並評估後續步驟。我真的無法評論更多。

We'll go next to Vikram Purohit with Morgan Stanley.

接下來我們將與摩根士丹利一起討論 Vikram Purohit。

This is (inaudible) on for Vikram and congrats approvals. I have a quick question about PPD. What do you expect the (inaudible) gross to net to be for Zurzuvae? And how long do you think you can you can get there?

這是 Vikram 的（聽不清），恭喜獲得批准。我有一個關於 PPD 的簡單問題。您預計 Zurzuvae 的（聽不清）淨毛收入是多少？您認為您需要多長時間才能到達那裡？

It's -- since we already talked about the idea that we're going to turn our intention to work on WACC and launch. It's too early to talk about gross to net.

因為我們已經討論過我們將把我們的意圖轉向 WACC 和發布的工作。現在談論毛淨值還為時過早。

We'll go next to Marc Goodman with Leerink.

我們將和 Leerink 一起去馬克·古德曼 (Marc Goodman) 旁邊。

My question is around MDD. And you -- in guidance from FDA, they talk about 2 drug placebo controlled studies that have to show duration of effect. And you clearly had that in one of your studies, but it's not clear that you had that in a second study. And I was curious if that was the reason that the FDA did not approve the MDD? And if that is the case or whatever the case is, are you and your partner has committed to doing another study in order to do whatever the FDA needs to get MDD?

我的問題是關於 MDD 的。而你——在 FDA 的指導下，他們談論了兩項藥物安慰劑對照研究，這些研究必須顯示效果的持續時間。在你的一項研究中顯然存在這一點，但尚不清楚你在第二項研究中是否存在這一點。我很好奇這是否就是 FDA 不批准 MDD 的原因？如果是這種情況或無論是什麼情況，您和您的伴侶是否已承諾進行另一項研究，以便採取 FDA 需要的任何措施來獲得 MDD？

Thanks for the question, Marc. As I said, we're extremely disappointed for patients with the CRL, and we don't agree with the FDA's views. So that's going to say right now. All we can say is what we did, which in accordance with FDA, we filed our NDA last year with what we believe was 6 of 7 positive studies and at the end point the oral-controlled studies. That was our belief set when we filed the NDA, of course. And we cannot just say with the CRL states as I've already said, which is that the application labs, substantial evidence of effectiveness and that additional study or studies are required. So we intend on evaluating the CRL and pursuing next steps in Biogen.

謝謝你的提問，馬克。正如我所說，我們對 CRL 患者感到非常失望，並且我們不同意 FDA 的觀點。所以現在要說的是。我們所能說的就是我們所做的，根據 FDA 的規定，我們去年提交了 NDA，我們認為 7 項積極研究中的 6 項以及最終的口服對照研究。當然，這是我們在提交保密協議時所設定的信念。我們不能像我已經說過的那樣，只對 CRL 狀態說，即需要應用實驗室、有效性的實質性證據以及需要進行額外的研究。因此，我們打算評估 CRL 並採取 Biogen 的後續措施。

But if you need to do another study, which the FDA is saying, are you -- we're going to do another study, we'll do whatever it takes to get MDD or it's that clear yet?

但如果你需要做另一項研究，正如FDA所說，我們將做另一項研究，我們會盡一切努力來獲得MDD，或者已經很明確了嗎？

So Marc, let me just repeat. We're disappointed for patients that we don't agree with the FDA. We're evaluating the feedback and reviewing next steps.

馬克，讓我重複一遍。對於我們不同意 FDA 的觀點，我們對患者感到失望。我們正在評估反饋並審查後續步驟。

We'll go next to Akash Tewari with Jefferies.

接下來我們將與 Jefferies 一起前往 Akash Tewari。

Congrats on the PPD approval. I guess in your collaboration agreement, it mentioned that Biogen could terminate the contract on a product-by-product basis by giving 150 days in advanced written notice. Is there a development juncture where Biogen wouldn't be able to terminate the agreement, let's say, for zuranolone? And have you received any notice from Biogen at this point? I just wanted to confirm.

恭喜 PPD 批准。我猜你們的合作協議中提到百健（Biogen）可以提前 150 天發出書面通知，逐個產品地終止合同。是否存在百健 (Biogen) 無法終止協議（例如 zuranolone）的開發時機？目前您收到百健（Biogen）的任何通知了嗎？我只是想確認一下。

Yes, Akash. I guess what I can say is there are termination provisions in the agreement. I can also say that after receiving the PPD approval and the CRL, we jointly worked on the press release that you saw committed to launch of Zurzuvae in the fourth quarter for PPD shortly after the DEA scheduling. So I'll leave it at that.

是的，阿卡什。我想我能說的是協議中有終止條款。我還可以說，在收到 PPD 批准和 CRL 後，我們共同製作了新聞稿，您可以看到承諾在 DEA 安排後不久的第四季度為 PPD 推出 Zurzuvae。所以我就這樣吧。

We'll go next to Tim Lugo with William Blair.

我們將和威廉·布萊爾一起去蒂姆·盧戈旁邊。

Can you walk us through the scheduling process in the next few months? It seems like most are viewing it as a formality. However, we've had rises in benzo, they're assuming abuse in recent years and sometimes class-wide issues can get wrapped up into single product discussions. So you just help us frame the risk around that process?

您能否向我們介紹一下未來幾個月的安排流程？似乎大多數人都將其視為一種形式。然而，我們的苯並類藥物有所增加，他們假設近年來濫用，有時全班範圍的問題可能會被納入單一產品的討論中。那麼您只是幫助我們圍繞該流程構建風險？

Yes. Thanks for the question, Tim. So the FDA refers to Zurzuvae for DEA for Schedule review. We anticipate that to occur within 90 days. And as you heard Laura say, we expect to have a Class IV label, which is not an issue for prescribers or for patients.

是的。謝謝你的提問，蒂姆。因此 FDA 將 Zurzuvae 提交給 DEA 進行時間表審查。我們預計這將在 90 天內發生。正如您聽到勞拉（Laura）所說，我們期望有 IV 級標籤，這對處方者或患者來說都不是問題。

Will go next to George Farmer with Scotiabank.

將與豐業銀行一起去喬治·法默（George Farmer）旁邊。

Two things with me real quickly. How long do you think that the sampling program will last as we think about modeling drug penetration in the market? And also, can you speak to your comfort level of risk to feeding newborns and if you've done any particular studies to address that?

有兩件事很快就發生在我身上。當我們考慮對市場上的藥物滲透進行建模時，您認為抽樣計劃會持續多久？另外，您能談談您對餵養新生兒的風險的舒適度嗎？您是否做過任何特定的研究來解決這個問題？

Yes. Thanks for the question, George. I'm glad for some new questions. Thank you. So let me start a little bit, and then I'll ask Chris to talk about sampling and then Laura to talk about breastfeeding. So if you take a step back, we believe that health care provider experience with Zurzuvae in their own hands, seeing the profound and rapid effects that we saw in clinical trials that Zurzuvae has the potential to have on models with PPD is critical to strategy. So physician or health care provider activation and that's where we use the sampling program. Chris, can you talk about -- you can't talk specific color on Houston and then we can turn it over to Laura for breastfeeding.

是的。謝謝你的提問，喬治。我很高興提出一些新問題。謝謝。讓我開始一點，然後我會請克里斯談論採樣，然後請勞拉談論母乳喂養。因此，如果您退後一步，我們相信醫療保健提供者在自己手中擁有Zurzuvae 的經驗，看到我們在臨床試驗中看到的Zurzuvae 對PPD 模型可能產生的深遠而快速的影響，這對策略至關重要。因此，醫生或醫療保健提供者的激活就是我們使用抽樣計劃的地方。克里斯，你能談談——你不能談論休斯頓的具體顏色，然後我們可以把它交給勞拉進行母乳喂養。

Yes. So Barry, what I can say is that, as in my prepared remarks, we see this as an early experience program that really focuses on giving physicians that experience in and around the time of launch once we have DEA scheduling. That's a finite window of opportunity for physicians to use that. The actual duration more later as we talk about our actual go-to-market strategy and the details of commercialization. But it is a finite window that we see that in around the time of launch.

是的。巴里，我能說的是，正如我準備好的發言中所說，我們認為這是一個早期體驗計劃，真正的重點是在 DEA 安排好後，在啟動時及前後為醫生提供體驗。對於醫生來說，使用它的機會是有限的。實際持續時間稍後我們將討論我們實際的上市策略和商業化的細節。但我們在發布前後看到這一點的時間是有限的。

And what I can add is we're not talking about all the markers, but it's likely in our quarterly calls after the launch of Zurzuvae for PPD, we'll be providing some color on how many samples are out there and how that's going. Laura, do you want to talk about the breastfeeding?

我可以補充的是，我們並不是在談論所有標記，但在推出用於 PPD 的 Zurzuvae 後的季度電話會議中，我們可能會提供一些關於現有樣本數量以及進展情況的信息。勞拉，你想談談母乳喂養嗎？

Sure. Sure, you raised an important question, George, given that this is going to be used in a population that's breastfeeding. Sage has done a clinical observation study and the results of those -- of that study showed that there's very low levels of Zurzuvae present in human milk. In fact, the calculated maximum relative to infant dose for Zurzuvae is less than 1%. So what it says in the label then is that a physician and patient should consider the development on health benefits of breastfeeding weighed with the potential exposure to Zurzuvae in the breast milk. It's really important that we have this data in the label. It differentiates this label from other drugs that are used off-label to treat MDD, where this data is either absent or the levels present in breast milk are much higher.

當然。當然，喬治，你提出了一個重要的問題，因為這將用於母乳喂養的人群。 Sage 進行了一項臨床觀察研究，該研究的結果表明，母乳中的 Zurzuvae 含量非常低。事實上，計算得出的 Zurzuvae 相對於嬰兒劑量的最大劑量小於 1%。因此，標籤中的內容是，醫生和患者應考慮母乳喂養對健康益處的發展，並權衡母乳中 Zurzuvae 的潛在暴露。我們在標籤中包含這些數據非常重要。它將這一標籤與其他用於治療重度抑鬱症的標籤外藥物區分開來，在這些藥物中，要么缺乏此數據，要么母乳中的含量要高得多。

We'll go next to Uy Ear with Mizuho.

我們將和Mizuho一起去Uy Ear旁邊。

I have two quick ones, if that's okay. So the first one, do you think it's easier now would only PPD indications for you to obtain value base? And second one, just could you sort of remind us in the collaboration with Biogen. What are -- are there any fees if you if the collaboration is terminated any payments in either directions you have to pay Biogen or Biogen have to pay you?

我有兩個快的，如果可以的話。那麼第一個問題，您認為現在僅通過 PPD 指示來獲得價值基礎是否更容易？第二個問題，您能否提醒我們與百健（Biogen）的合作。如果合作終止，您必須向百健（Biogen）支付任何費用，或者百健（Biogen）必須向您支付任何費用，有什麼費用嗎？

Yes. Let me start with the second, Uy. So there certainly -- there are termination provisions in the contract that's about as far as I can go on that one. And then again, very insightful. We have -- as I mentioned, we have many tailwinds for PPD focused launch. It's a large unmet need with about 0.5 million women in the U.S. experience symptoms each year, only about half of whom are diagnosed per year. So a real big opportunity on improving diagnosis. This will be the first and only oral treatment approved for women with PPD. So that's a big advantage. And then talking to health care providers who prescribe they're anxious to have a product like Zurzuvae.

是的。讓我從第二個開始，Uy。因此，合同中肯定有終止條款，這是我所能做到的。話又說回來，非常有洞察力。正如我所提到的，我們有很多推動以 PPD 為重點的發布的有利因素。這是一個巨大的未滿足的需求，美國每年約有 50 萬女性出現症狀，其中每年只有大約一半被診斷出來。這是改善診斷的真正巨大機會。這將是第一個也是唯一一個被批准用於產後抑鬱症女性的口服治療方法。所以這是一個很大的優勢。然後與醫療保健提供者交談，他們表示他們渴望擁有像 Zurzuvae 這樣的產品。

The issue they have today if they can't get access to ZULRESSO is that the products they use take weeks to work, if at all. And as we know, many patients cycle through many different drugs. And these -- the term that you say often come with comorbidities, weight gain, receptor dysfunction, GI impact. So at a prescriber level, let's say an OB/GYN level the course of treatment just doesn't fit into how they're dealing with mom and baby, whereas Zurzuvae could be the solution to that problem. And certainly, payers have been historically supportive of the syndication. And as we mentioned, maternal mental health is on everybody's mind. It's been on television almost every night. It's at every state level for policies, and we have now the first world treatment that could be a solution set, at least in PPD for maternal mental health and the policies that are happening at the statewide level.

如果他們無法訪問 ZULRESSO，他們今天遇到的問題是，他們使用的產品需要數週時間才能發揮作用（如果有的話）。正如我們所知，許多患者會循環使用許多不同的藥物。而這些——你所說的這個術語經常伴隨著合併症、體重增加、受體功能障礙、胃腸道影響。因此，在處方者層面，假設在婦產科醫生層面，治療過程並不適合他們對待媽媽和嬰兒的方式，而 Zurzuvae 可能是解決該問題的方法。當然，付款人歷來都支持該聯合組織。正如我們提到的，孕產婦心理健康是每個人都關心的問題。幾乎每晚電視上都會播放這件事。這是每個州一級的政策，我們現在擁有第一個可以作為解決方案的世界治療方法，至少在孕產婦心理健康的 PPD 和全州一級正在實施的政策方面是這樣。

We'll go next to Yatin Suneja with Guggenheim.

接下來我們將前往古根海姆博物館 (Yatin Suneja)。

And let me add my congrats on the approval. So just 2 questions, 1 clarification and then 1 follow-up. So with regard to the sampling comment, it is our understanding that the control substance has limitation from a sampling perspective. So could you clarify that would you be able to sample it and also -- yes, just that. And then with regard to the commercial build, I understand, you provide us more detail once you launch. But let's say, if you got approved for MDD and that requires 100 sales rep. Just trying to understand the commercial build around PPD, is it 20 sales rep, 30 sales reps or 20% less, just some sort of ballpark? Just trying to gauge what the spend will be also as we model it?

讓我對獲得批准表示祝賀。所以只有 2 個問題，1 個澄清，然後 1 個跟進。因此，對於抽樣意見，我們的理解是，從抽樣角度來看，控制物質存在局限性。那麼您能否澄清一下，您是否能夠對其進行採樣以及——是的，僅此而已。然後，關於商業版本，據我了解，您在啟動後會向我們提供更多詳細信息。但假設您獲得了 MDD 批准，並且需要 100 名銷售代表。只是想了解圍繞 PPD 的商業構建，是 20 名銷售代表、30 名銷售代表還是減少 20%，只是某種大概？只是想在我們建模時估算一下支出是多少？

Yes. So let me quickly answer both questions, I know we're getting at the top of the hour. So what we said about the commercial build is that we're thinking big, but starting with a very focused way, clearly, much more focused in PPD than -- in PPD and MDD, but we really can't provide numbers. You also heard from Kimi that we're prioritizing our pipeline and kind of when we'll resize the organization appropriate for this opportunity in the pipeline in front of us. So we'll communicate that in the next month or so. In terms of sampling, there are certain limitations of controlled states, whether you can use a natural sample or a voucher, but we don't see that being a limitation to the concept on sampling program.

是的。讓我快速回答這兩個問題，我知道我們正處於最重要的時刻。因此，我們關於商業構建的說法是，我們正在考慮大局，但從一種非常專注的方式開始，顯然，比 PPD 和 MDD 更關注 PPD，但我們確實無法提供數字。您還從 Kimi 那裡聽說，我們正在優先考慮我們的管道，並且我們將在某種程度上調整組織規模，以適應我們面前管道中的這個機會。因此，我們將在下個月左右進行溝通。在抽樣方面，無論是使用自然樣本還是憑證，受控狀態都存在一定的限制，但我們不認為這是對抽樣計劃概念的限制。

This does conclude the question-and-answer portion of today's call. I would like to turn the presentation back over to Barry Greene.

今天電話會議的問答部分到此結束。我想把演講轉回給巴里·格林。

Thank you, Ruth, and thanks again to everyone for joining us today. This is a special day for Sage, Biogen and all the women with PPD who stand to benefit from Zurzuvae. We appreciate the continued support of all stakeholders, and we look forward to providing more updates in the coming months. Thanks again, everyone, and have a great day.

謝謝你，露絲，並再次感謝大家今天加入我們。對於 Sage、Biogen 以及所有從 Zurzuvae 中受益的產後抑鬱症女性來說，這是一個特殊的日子。我們感謝所有利益相關者的持續支持，並期待在未來幾個月提供更多更新。再次感謝大家，祝您有美好的一天。

Goodbye.

再見。

This does conclude today's call. You may now disconnect.

今天的電話會議到此結束。您現在可以斷開連接。