Mind Medicine (MindMed) Inc (MNMD) 2024 Q4 法說會逐字稿

Good morning and welcome to the Mind Medicine, fourth quarter and year-end 2024 financial results corporate update conference call. Currently all participants are in listen-only mode. This call is being webcast live on the investors and media section of MindMed's website at mindmed.co, and a recording will be available after the call. I would like to introduce Stephanie Fagan, Chief Corporate Affairs Officer of MindMed. Please go ahead.

早安，歡迎參加 Mind Medicine 2024 年第四季和年終財務業績公司更新電話會議。目前所有參與者都處於只聽模式。本次電話會議將在 MindMed 網站 mindmed.co 的投資者和媒體部分進行網路直播，會議結束後將提供錄音。我想介紹 MindMed 首席企業事務長 Stephanie Fagan。請繼續。

Thank you, operator, and good morning, everyone.

謝謝接線員，大家早安。

Thank you for joining us for a discussion of MindMed's fourth quarter and year-end 2024 business highlights and financial results.

感謝您加入我們討論 MindMed 2024 年第四季和年末的業務亮點和財務表現。

Leading the call today will be Rob Barrow, our Chief Executive Officer, and he will be joined by Dr. Dan Karlin, our Chief Medical Officer.

今天的電話會議主持人將是我們的執行長 Rob Barrow，我們的首席醫療官 Dan Karlin 博士也將參加會議。

After our prepared remarks, we will open the call for Q&A. An audio recording and webcast replay for today's conference call will also be available online as detailed in the press release announcement for this call.

在我們準備好發言之後，我們將開始問答環節。今天電話會議的錄音和網路直播重播也將在網路上提供，詳情請參閱本次電話會議的新聞稿公告。

During today's call, we will be making certain forward-looking statements including without limitation, statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, our anticipated cash runway, and our future expectations, plans, partnerships, and prospects. These statements are subject to various risks such as changes in market conditions and difficulties associated with research and development and regulatory approval processes. These and other risk factors are described in the filings made with the SEC and the applicable Canadian Securities Regulators, including our annual report on Form 10-k filed today.

在今天的電話會議中，我們將做出某些前瞻性陳述，包括但不限於有關我們候選產品的潛在安全性、有效性、監管和臨床進展、我們預期的現金流以及我們未來的期望、計劃、合作夥伴關係和前景的陳述。這些聲明受到各種風險的影響，例如市場條件的變化以及與研發和監管審批流程相關的困難。這些和其他風險因素在向美國證券交易委員會和適用的加拿大證券監管機構提交的文件中有所描述，包括我們今天提交的 10-k 表格年度報告。

Forward-looking statements are based on the assumptions, opinions, and estimates of management at the date the statements are made, including the non-occurrence of the risks and uncertainties that are described in the filings made with the SEC and the applicable Canadian Securities regulators or other significant events occurring outside of MindMed's normal course of business.

前瞻性陳述是基於管理層在陳述之日的假設、意見和估計，包括向美國證券交易委員會和適用的加拿大證券監管機構提交的文件中所描述的風險和不確定性的未發生，或在 MindMed 正常業務範圍之外發生的其他重大事件。

You are cautioned not to place undue reliance on these forward-looking statements, which are made as of today, March 6, 2025.

請注意不要過度依賴這些前瞻性陳述，這些陳述是截至 2025 年 3 月 6 日做出的。

MindMed disclaims any obligation to update such statements even if management use change except as required by law. With that, let me turn the call over to Rob.

即使管理使用發生變化，MindMed 也不承擔更新此類聲明的任何義務，除非法律要求。說完這些，讓我把電話轉給羅布。

Thank you, Stephanie and everyone for joining our call today.

感謝史蒂芬妮和大家今天參加我們的電話會議。

2024 marked a year of unparalleled progress for MindMed, underscoring our leadership and advancing new treatments for brain health. We successfully achieved key milestones, positioning us to potentially deliver multiple clinical readouts from our MM120 phase 3 program in 2026.

2024 年是 MindMed 空前進步的一年，彰顯了我們的領導地位並推動了腦部健康新療法的發展。我們成功實現了關鍵里程碑，使我們能夠在 2026 年從我們的 MM120 第 3 階段計劃中提供多個臨床讀數。

A year ago, we announced positive results from our phase 2b study of MM120 in generalized anxiety disorder, or GAD, which showed statistically significant and durable improvements in mean Hamilton Anxiety scale, or HAM-A, and Clinical Global Impression Severity, or CGIS scores for twelve weeks after a single dose of MM120.

一年前，我們宣布了 MM120 治療廣泛性焦慮症 (GAD) 的 2b 期研究的積極成果，結果顯示，在單劑量使用 MM120 後十二週內，漢密爾頓焦慮量表 (HAM-A) 平均評分和臨床總體印象嚴重程度 (CGIS) 評分均有統計學上顯著且持久的改善。

We also announced the results of a pharmacokinetic bridging study of our orally dissolving tablet formulation of MM120, our intended commercial formulation, which we are also using in our phase 3 studies.

我們也發表了我們口腔溶解片配方 MM120 的藥物動力學橋接研究的結果，這是我們預期的商業配方，我們也在 3 期研究中使用該配方。

Additionally, in 2024, we secured a new formulation patent on MM120 ODT extending our intellectual property protection through at least 2041. Based on the strength of our data and the seriousness of GAD, FDA granted our MM120 GAD program breakthrough therapy designation, indicating its potential to represent a substantial improvement over currently available therapies.

此外，2024 年，我們獲得了 MM120 ODT 的新配方專利，將我們的智慧財產權保護期限至少延長至 2041 年。根據我們數據的強度和 GAD 的嚴重性，FDA 授予我們的 MM120 GAD 計劃突破性療法稱號，表明它有可能比目前可用的療法有實質性的改進。

Our development approach prioritizes designing clean studies that yield clear results and are efficient to operationalize. This is exemplified by our bold decision early in development to study MM120 as a stand-alone treatment, and our streamlined phase 3 clinical trial designs, which aim to replicate the rapid durable response observed in our phase 2b study.

我們的開發方法優先設計清晰的研究，以產生清晰的結果並有效率地實施。我們在開發早期就做出了大膽的決定，將 MM120 作為獨立治療方法進行研究，並簡化了 3 期臨床試驗設計，旨在複製我們在 2b 期研究中觀察到的快速持久反應，這證明了這一點。

A pivotal program in GAD includes two phase 3 studies, Voyage and Panorama. As we previously announced, we are very excited to have already successfully dosed patients in both studies, and we have seen strong enthusiasm from clinical sites and patients as recruitment has continued to ramp up. These sites include some of the highest performing enrollers from our phase 2b study, and we were very encouraged by early enrollment trends.

GAD 中的一個關鍵項目包括兩個第三階段的研究，即 Voyage 和 Panorama。正如我們之前宣布的那樣，我們非常高興已經在這兩項研究中成功為患者給藥，隨著招募工作的不斷加強，我們看到了臨床站點和患者的強烈熱情。這些站點包括我們 2b 期研究中表現最好的招募者，早期招募趨勢令我們感到非常鼓舞。

We're also on track to do participants and emerge our first phase 3 study for the treatment of Major Depressive Disorder, or MDD in the first half of this year. This phase 3 program closely aligns with our GAD program with a protocol that allows for streamlined and efficient patient enrollment.

我們也計劃在今年上半年招募參與者並進行針對重度憂鬱症（MDD）治療的第一階段 3 期研究。該 3 期計劃與我們的 GAD 計劃緊密結合，其協議允許簡化和高效的患者入組。

These two indications, GAD and MDD, affect approximately 51 million adults in the US and represent two of the most significant unmet medical needs in psychiatry.

GAD 和 MDD 這兩種疾病影響了美國約 5,100 萬成年人，代表了精神病學領域最重大的未滿足醫療需求。

We believe MM120 could offer a differentiated and compelling option in both GAD and MDD, potentially positioning it as a best in class and first in class treatment option.

我們相信 MM120 可以為 GAD 和 MDD 提供差異化且引人注目的選擇，有可能使其成為同類最佳和一流的治療選擇。

We aspire to deliver a truly transformative treatment that has the potential to change the trajectory of the ongoing brain health epidemic. In fact, in our research with providers, they have shared their belief that the availability of psychedelics will radically transform treatment for GAD and MDD.

我們渴望提供一種真正具有變革性的治療方法，有可能改變正在發生的大腦健康流行病的軌跡。事實上，在我們與供應商的研究中，他們都相信迷幻藥的出現將從根本上改變 GAD 和 MDD 的治療方法。

Over the past year, we have been dedicated to broadening the awareness and understanding of these disorders and sharing our findings in a number of key medical meetings such as the American Psychiatric Association's annual meeting, the International Society for Health Economics and Outcomes Research annual meeting, and the American College of Neuropsychopharmacology's annual meeting.

在過去的一年裡，我們致力於加深人們對這些疾病的認識和理解，並在許多重要的醫學會議上分享我們的研究成果，例如美國精神醫學會年會、國際衛生經濟與成果研究學會年會和美國神經精神藥理學會年會。

We continue to generate evidence that underscores the significant economic and social burden of GAD in the United States, including a higher healthcare utilization and costs, as well as reduced work productivity. These findings highlight the substantial impact of GAD which has largely been underappreciated.

我們不斷提供證據，強調 GAD 對美國帶來的巨大經濟和社會負擔，包括更高的醫療保健利用率和成本，以及工作效率下降。這些發現凸顯了廣泛性焦慮症 (GAD) 的巨大影響，但這種影響在很大程度上並未得到充分重視。

I couldn't be more thrilled with the progress we've made this past year. As we look forward, 2025 will be a year of execution, focused on our phase 3 programs in GAD and MDD and preparing for our three pivotal trial readouts in 2026.

我對我們在過去一年中取得的進步感到非常興奮。展望未來，2025 年將是執行的一年，重點關注 GAD 和 MDD 的第三階段項目，並為 2026 年的三個關鍵試驗讀數做準備。

We have a strong dedicated team in place and continue to build a leading organization with best in class execution. Over the past year, we have also strengthened our financial position, having raised approximately $250 million in gross proceeds and gained the support of a number of top institutional investors.

我們擁有一支強大的專業團隊，並將繼續打造具有一流執行力的領先組織。在過去的一年裡，我們也加強了財務狀況，籌集了約 2.5 億美元的總收益，並獲得了許多頂級機構投資者的支持。

We expect our current cash and cash equivalents to provide sufficient funding into 2027 with a cash runway that extends at least twelve months beyond the first phase 3 topline data readout for MM120 and GAD.

我們預計，我們目前的現金和現金等價物將為 2027 年提供足夠的資金，現金流將至少持續到 MM120 和 GAD 第一階段 3 期頂線數據讀數之後的十二個月。

Now let me turn the call over to our Chief Medical Officer, Doctor Dan Karlin, to discuss our clinical development programs in more detail. Dan.

現在，讓我將電話轉給我們的首席醫療官 Dan Karlin 博士，以更詳細地討論我們的臨床開發計劃。擔。

Thanks, Rob. As Rob just mentioned, we have already dosed participants in both of our pivotal phase 3 clinical studies for GAD Voyage, and Panorama.

謝謝，羅布。正如 Rob 剛才提到的，我們已經對 GAD Voyage 和 Panorama 兩個關鍵的 3 期臨床研究的參與者進行了劑量測定。

We are highly encouraged by the early enrollment trends and continue to expect topline readouts from Voyage in the first half of 2026 and Panorama in the second half of 2026.

我們對早期的招生趨勢感到非常鼓舞，並繼續預計 Voyage 將在 2026 年上半年公佈營收數據，Panorama 將在 2026 年下半年公佈營收數據。

Each study consists of two parts. Part a twelve-week randomized double blind placebo-controlled parallel group study assessing the efficacy and safety of MM120 versus placebo, and Part B, forty-week extension period with opportunities for open label treatment designed to provide important long-term data on the durability and response patterns with MM120.

每項研究由兩部分組成。第 1 部分為為期 12 週的隨機雙盲安慰劑對照平行組研究，評估 MM120 與安慰劑相比的療效和安全性；第 2 部分為為期 40 週的延長期，提供開放標籤治療的機會，旨在提供有關 MM120 的持久性和反應模式的重要長期數據。

In Voyage, we expect to enroll approximately 200 participants who will be randomized 1:1 to receive MM120 100-microgram or placebo, while in panorama we expect to enroll approximately 250 participants who will be randomized 2:1:2 to receive MM120 100-microgram, 50-microgram, or placebo.

在 Voyage 研究中，我們預計將招募約 200 名參與者，他們將以 1:1 的比例隨機分配接受 MM120 100 微克或安慰劑；而在全景研究中，我們預計將招募約 250 名參與者，他們將按 2:1:2 的比例隨機分配接受 MM120 100 微克、微克或微克。

As Rob mentioned, we have taken an intentional and thoughtful approach to our development strategy, which has been informed by our team's deep experience in developing novel psychiatric therapies and through close collaboration with FDA. Our protocols are designed with operational input from sites and participants and specific attention to enabling enrollment so that we are able to rapidly recruit a representative sample of participants.

正如 Rob 所提到的，我們對我們的發展策略採取了有意而深思熟慮的方法，這種方法源於我們團隊在開發新型精神病療法方面的豐富經驗以及與 FDA 的密切合作。我們的協議是根據站點和參與者的操作輸入而設計的，特別注重實現註冊，以便我們能夠快速招募具有代表性的參與者樣本。

Our phase 3 studies in GAD closely resemble the design and execution used in our phase 2b study. In both Voyage and Panorama, the primary endpoint is the change from baseline to week twelve in the HAM-A, which was the outcome measure used for the approval of the currently available GAD therapies.

我們對 GAD 的 3 期研究與我們 2b 期研究中使用的設計和執行非常相似。在 Voyage 和 Panorama 中，主要終點是 HAM-A 從基線到第十二週的變化，這是用於批准目前可用的 GAD 療法的結果測量標準。

These trials incorporate important methods such as the use of central raiders who are blinded to both treatment assignment and visit number, questionnaires to assess potential expectancy bias, and in the case of panorama, multiple control arms, including a lower dose control that is perceivable and was previously tested.

這些試驗採用了重要的方法，例如使用對治療分配和訪問次數都一無所知的中央襲擊者、評估潛在預期偏差的問卷，以及在全景的情況下，多個對照組，包括可感知的且之前經過測試的較低劑量對照。

This approach builds on our phase 2b data where we demonstrated that despite functional and binding of participants at all tested doses, the lower doses, including 50-microgram, did not demonstrate a meaningful clinical response. We believe this evidence strongly supports our view that the anxiolytic effect of MM120 cannot be attributable to functional and blinding, and thus the measured effect reliably represents a true drug effect.

這種方法建立在我們的 2b 期數據之上，我們證明，儘管參與者在所有測試劑量下都具有功能性和結合性，但較低劑量（包括 50 微克）並未表現出有意義的臨床反應。我們相信，這項證據有力地支持了我們的觀點，即 MM120 的抗焦慮作用不能歸因於功能性和致盲性，因此測量的效果可靠地代表了真正的藥物作用。

These trials were designed to have 90% power to detect a five-point improvement over placebo based on certain statistical assumptions, where in the phase 2b trial, we observed an almost eight-point improvement for MM120 over placebo at week twelve.

這些試驗旨在根據某些統計假設以 90% 的功效檢測出比安慰劑高出 5 個百分點的改善，其中在 2b 期試驗中，我們觀察到第 12 週時 MM120 比安慰劑高出近 8 個百分點。

We are using an adaptive design in our phase 3 studies that includes an interim blinded sample size re-estimation which allows for increased enrollment of up to 50% in each trial. This approach helps to adjust for any unexpected variability in nuisance parameters, specifically dropout rates and pooled variants of [MA] response, maintaining statistical power, and enhancing the interpretability of our results if needed.

我們在第 3 階段研究中採用了自適應設計，其中包括中期盲樣本量重新估計，這使得每次試驗的入組率可以增加高達 50%。這種方法有助於調整幹擾參數中的任何意外變化，特別是 [MA] 響應的退出率和匯總變量，保持統計能力，並在需要時增強結果的可解釋性。

Key elements such as inclusion and exclusion criteria will largely mirror our successful phase 2b study of MM120 and GAD incorporating exclusion criteria around the recency or total use of psychedelics to ensure a representative sample is recruited.

納入和排除標準等關鍵要素將在很大程度上反映我們對 MM120 和 GAD 的成功 2b 期研究，該研究結合了圍繞迷幻藥的近期使用或總體使用情況的排除標準，以確保招募到具有代表性的樣本。

We also conduct comprehensive safety assessments and labs before and after the administration of MM120 and ensure the collection of all adverse events.

我們還在使用 MM120 之前和之後進行全面的安全評估和實驗室檢查，並確保收集所有不良事件。

Turning to our MDD program with MM120, we remain on track to dose our first participant in the first half of 2025 with data expected in the second half of 2026. Just like in our GAD program, we anticipate that our MDD program will consist of two pivotal clinical studies. Our first study emerge will be comprised of two parts. Part a twelve-week randomized double blind placebo-controlled parallel group study assessing the efficacy and safety of a single dose of MM120 versus placebo, and Part B, a forty-week extension period during which participants will be eligible for open label treatment with MM120 subject to meeting eligibility requirements.

談到我們的 MM120 MDD 項目，我們仍有望在 2025 年上半年為第一位參與者進行給藥，並預計在 2026 年下半年獲得數據。就像我們的 GAD 計畫一樣，我們預計我們的 MDD 計畫將包括兩項關鍵的臨床研究。我們的第一項研究將由兩部分組成。第 1 部分為為期 12 週的隨機雙盲安慰劑對照平行組研究，評估單劑量 MM120 與安慰劑相比的療效和安全性；第 2 部分為為期 40 週的延長期，在此期間，參與者將有資格接受 MM120 的開放標籤治療，但須符合資格要求。

In a merge, we plan to enroll at least 140 participants with a primary diagnosis of MDD randomized 1:1 to receive MM120 100-microgram or placebo.

在合併中，我們計劃招募至少 140 名主要診斷為 MDD 的參與者，以 1:1 的比例隨機分配接受 MM120 100 微克或安慰劑。

The primary endpoint in a merge is the change from baseline in Montgomery Asberg Depression Rating Scale Score, or MADRS at week six between MM120 100-microgram and placebo.

合併的主要終點是蒙哥馬利·阿斯伯格憂鬱量表評分（MM120 100 微克與安慰劑之間第六週 MADRS 與基線的變化。

The design and timing of the second MDD trial will be informed by the progress from a merge and additional regulatory discussions.

第二次 MDD 試驗的設計和時間將根據合併進展和其他監管討論的結果來確定。

With that, I'll turn the call back over to Rob to discuss our fourth quarter and year-end financial results. Rob.

說完這些，我將把電話轉回給羅布，討論我們的第四季和年終財務表現。搶。

Thanks, Dan.

謝謝，丹。

Turning to our finding results for the year ending December 31, 2024, we ended the year with cash and cash equivalents totaling $273.7 million compared to $99.7 million as of December 31, 2023.

回顧我們截至 2024 年 12 月 31 日的年度調查結果，截至該年度，我們的現金和現金等價物總額為 2.737 億美元，而截至 2023 年 12 月 31 日為 9970 萬美元。

Overall, we believe that our cash and cash equivalents as of December 31, 2024, will be sufficient to fund our operations into 2027 and at least twelve months beyond the top line data readout for our first phase three trial of MM120 in GAD.

總體而言，我們相信，截至 2024 年 12 月 31 日的現金和現金等價物將足以支持我們到 2027 年的運營，並且至少支持我們在 GAD 中對 MM120 進行第一階段三期試驗的頂線數據讀數之後的十二個月。

Research and development expenses were $21.8 million for the three months ended December 31, 2024, compared to $11.5 million for the three months into December 31, 2023, an increase of $10.3 million.

截至 2024 年 12 月 31 日的三個月，研發費用為 2,180 萬美元，而截至 2023 年 12 月 31 日的三個月為 1,150 萬美元，增加了 1,030 萬美元。

R&D expenses were $65.3 million for the year ended December 31, 2024, compared to $52.1 million for the year ended December 31, 2023, an increase of $13.2 million.

截至 2024 年 12 月 31 日止年度的研發費用為 6,530 萬美元，而截至 2023 年 12 月 31 日止年度的研發費用為 5,210 萬美元，增加了 1,320 萬美元。

The increase was primarily due to expenses related to our pivotal MM120 programs, phase 1 MM402 program, and an increase of internal personnel costs, partially offset by a decrease in expenses related to pre-clinical activities.

成長的主要原因是與我們的關鍵 MM120 項目、第一階段 MM402 項目相關的費用以及內部人員成本的增加，但部分被與臨床前活動相關的費用的減少所抵消。

We anticipate R&D expenses to ramp up in 2025 due to the cost associated with running three pivotal phase 3 studies.

我們預計，由於進行三項關鍵的 3 期研究的相關成本，2025 年的研發費用將會增加。

General and administrative expenses were $10.7 million for the three months ended December 31, 2024, and were the same for the three months ended December 31, 2023.

截至 2024 年 12 月 31 日的三個月的一般及行政費用為 1,070 萬美元，與截至 2023 年 12 月 31 日的三個月持平。

G&A expenses were $38.6 million for the year ended December 31, 2024, compared to $41.7 million for the year ended December 31, 2023, a decrease of $3.1 million. The decrease was primarily attributable to reduced professional services, fees and expenses, partially offset by increased stock-based compensation expense and costs associated with pre-commercial activities.

截至 2024 年 12 月 31 日止年度的一般及行政費用為 3,860 萬美元，而截至 2023 年 12 月 31 日止年度的一般及行政費用為 4,170 萬美元，減少了 310 萬美元。下降的主要原因是專業服務、費用和開支的減少，但股票薪酬費用和與商業前活動相關的成本的增加部分抵消了這一減少。

The company's net loss for the three months ended December 31, 2024, was $34.7 million compared to $23.8 million for the same period in 2023, an increase of $10.9 million.

截至 2024 年 12 月 31 日的三個月，該公司的淨虧損為 3,470 萬美元，而 2023 年同期為 2,380 萬美元，增加了 1,090 萬美元。

The company's net loss for the year ended December 31, 2024, was $108.6 million compared to $95.7 million for the same period in 2023, an increase of $12.9 million.

該公司截至 2024 年 12 月 31 日止年度的淨虧損為 1.086 億美元，而 2023 年同期的淨虧損為 9,570 萬美元，增加了 1,290 萬美元。

The increase was primarily attributed to research and development expenses associated with our MM120 and MM402 programs.

成長主要歸因於與我們的 MM120 和 MM402 項目相關的研發費用。

In closing, I'm incredibly proud of the progress we have made over the past year at MindMed. We believe MM120 is uniquely positioned to potentially offer a novel and highly differentiated treatment option for people living with brain health disorders.

最後，我對 MindMed 在過去一年中所取得的進步感到無比自豪。我們相信 MM120 具有獨特的優勢，可以為患有腦部健康障礙的人提供一種新穎且高度差異化的治療選擇。

None of our progress would have been possible without the dedication of our exceptional team. I want to thank them for their continued efforts and commitment to our mission.

如果沒有我們傑出團隊的奉獻，我們的進步就不可能實現。我要感謝他們為我們的使命所做的持續努力和承諾。

With that, I'd like to thank you all again for joining us today, and the team and I are happy to take your questions.

最後，我想再次感謝大家今天的參與，我和我的團隊很樂意回答大家的問題。

Thank you. If you'd like to ask a question, please press 11. (Operator Instructions)

謝謝。如果您想提問，請按 11。（操作員指示）

Our first question comes from Marc Goodman with Leerink. Your line is open.

我們的第一個問題來自 Leerink 的 Marc Goodman。您的線路已開通。

Hi, this is Madhu on the line for Marc. I think some people we speak with are trying to get a better understanding of which GAD patients would be likely to want to use MM120 over other available options once it could be eventually approved. And so just curious, would this be for patients who strictly don't respond to other available therapies or patients past a certain severity level. If you could share any insights that you have on that, maybe from market research or, just in terms of the patients that are looking to enroll in these studies, that would be great.

你好，我是 Madhu，找 Marc。我認為我們交談過的一些人正在試圖更好地了解哪些 GAD 患者可能希望在 MM120 最終獲得批准後使用 MM120，而不是其他可用選項。所以只是好奇，這是否適用於對其他可用療法沒有反應的患者或超過一定嚴重程度的患者。如果您可以分享您對此的任何見解，也許是從市場研究的角度，或者只是從希望參加這些研究的患者的角度，那就太好了。

Thank you.

謝謝。

Yes, thanks so much, Madhu, and I'll turn it over to Dan, in just a second. I think at a very high level, certainly the indication we're pursuing, which is a broad label for all generalized anxiety disorder patients would enable access much more broadly than if we had a severely restricted criteria on the label. Certainly, there are a pair dynamic that come into play, and we've had really encouraging. Signs in that research just based on the relative lack of treatments for GAD and the long time since any new treatments have been introduced and the overall severity of that population. But maybe Dan, if you want to add some clarity there as well.

是的，非常感謝，Madhu，我馬上就把麥克風交給 Dan。我認為，從非常高的層面上來說，我們所追求的適應症，即為所有廣泛性焦慮症患者提供一個廣泛的標籤，這將比我們對標籤設置嚴格限制的標準更廣泛地普及。當然，存在著一種相互作用，而且我們確實感到非常鼓舞。該研究的跡象僅基於對 GAD 的治療相對缺乏、自引入任何新療法以來已經很長時間以及該人群的整體嚴重程度。但也許丹，如果你也想在那裡增加一些清晰度。

Yes, absolutely, and I think that there's a really interesting. A point there which is that the sorts of patients who would be interested in accessing the drug is a really broad swath of the population, the poor folks with diagnosed GAD tolerability and efficacy of existing drugs like SSRIs is pretty unsatisfactory. SSRIs have never been particularly effective against anxiety cluster symptoms either in GAD or MDD. So, what we see both in market research but also in who presents to enroll in our studies is that there are people with severe GAD. There are people with moderate GAD. There are people who have had prior treatments, including SSRIs or psychotherapy. There are people who haven't had those treatments before either because they didn't want them or because their GAD wasn't recognized. So, we see there being both broad appeal and of course based on the efficacy we've seen in phase 2b, the ability to really help a broad swath of patients.

是的，絕對如此，我認為這真的很有趣。需要指出的是，對這種藥物感興趣的患者群體非常廣泛，被診斷出患有 GAD 的貧困人群對 SSRI 等現有藥物的耐受性和療效相當不令人滿意。無論是 GAD 或 MDD，SSRI 類藥物對焦慮叢集症狀都沒有特別的效果。因此，我們在市場調查以及參與我們研究的人員中都發現，有些人患有嚴重的廣泛性焦慮症。有些人患有中度廣泛性焦慮症。有些人曾接受過治療，包括 SSRI 或心理治療。有些人之前沒有接受過這些治療，要么是因為他們不想接受治療，要么是因為他們患有 GAD，而這種治療未被發現。因此，我們認為它不僅具有廣泛的吸引力，而且當然基於我們在第 2b 階段看到的療效，它能夠真正幫助廣大患者。

Now the realistic nature of a payer supported commercial market is that there are likely to be step therapy requirements. So, what you see often with new treatments in the class, even new treatments that have a mechanism that's similar to existing treatments or the same as existing treatments is a requirement to have been failed by one or more existing treatments, but given the efficacy that we're seeing, given the appeal of having a single treatment with no lingering adverse events, we think that the demand side will be quite high.

現在，付款人支持的商業市場的現實性質是可能會有逐步治療要求。因此，您經常會看到此類新療法，即使是具有與現有療法相似或相同的機制的新療法，也需要被一種或多種現有療法所失敗，但考慮到我們所看到的療效，考慮到單一療法沒有揮之不去的不良事件的吸引力，我們認為需求方會相當高。

Thank you.

謝謝。

Thank you. Our next question comes from Gavin Clark-Gartner with Evercore ISI. Your line is open.

謝謝。我們的下一個問題來自 Evercore ISI 的 Gavin Clark-Gartner。您的線路已開通。

Hey guys, congrats on the progress and thanks for taking the questions.

嘿，大家好，祝賀你們取得的進展，感謝你們回答問題。

First, I just wanted to ask, are you planning to give more granular enrollment updates for both of the GAD trials over the course of this year? Or is the next update that we should expect, enrollment completion?

首先，我只想問一下，您是否計劃在今年為兩項 GAD 試驗提供更詳細的招生更新資訊？或者我們應該期待的下一次更新是註冊完成？

Yes, thank, thanks so much, Kevin. We haven't yet provided the exact guidance that we would expect to follow a similar, pattern as industry standards and as we did in our phase two study, where we, as we approach the end of enrollment, we were able to announce that but, certainly as we have any material updates, we would be disclosing those.

是的，謝謝，非常感謝，凱文。我們尚未提供確切的指導，我們期望遵循與行業標準類似的模式，就像我們在第二階段的研究中所做的那樣，當我們接近招生結束時，我們能夠宣布這一點，但是，當然，當我們有任何重大更新時，我們將會披露這些。

Got it. That makes sense. Separately, just on the sample size re-estimation analysis, I wanted to confirm that there's no alpha used, no futility criteria, and also ask what you think the likelihood of the trial being upsized a little bit is and when this analysis roughly may occur.

知道了。這很有道理。另外，僅在樣本量重新估計分析中，我想確認沒有使用 alpha，沒有無效性標準，同時詢問您認為試驗規模稍微擴大的可能性是多少，以及這種分析大致何時可能發生。

Yes, great question. The way that the standard size re-estimation is designed is a no alpha spin blinded re-estimation, and the damages is only based on the nuisance parameters, the dropout rate and the pulled variance of the standard or the pull variants of HAM-A outcomes. So, we can't provide exact timing for when that would occur other than upon the completion of, about half the patients, about 100 patients who make it through week twelve, is when we anticipate to run that analysis.

是的，很好的問題。標準尺寸重新估計的設計方式是無 alpha 自旋盲重新估計，並且損害僅基於幹擾參數、輟學率和標準的拉動方差或 HAM-A 結果的拉動變體。因此，我們無法提供確切的時間，除非我們預計在大約一半的患者（大約 100 名度過第十二週的患者）完成後進行分析。

But certainly, no futility, no spend of alpha, and it's really just to ensure that power is maintained if any of those nuisance parameters are outside of our estimates. Now, the estimates we have, we feel quite confident and based on, a long history of the historical norms in this population and also analyzing the data from our phase 2 clinical trial. So, we feel quite confident in in the assumptions we've made at baseline, but it just adds an additional layer of protection in the event there is some kind of surprise on either the variance or on the dropout rate.

但可以肯定的是，這不是徒勞的，也不會浪費阿爾法，這實際上只是為了確保當任何干擾參數超出我們的估計時，能夠維持權力。現在，我們對所得到的估計非常有信心，而這些估計是基於對該族群的長期歷史規範以及我們第二階段臨床試驗的數據的分析。因此，我們對基線時所做的假設非常有信心，但它只是在變異數或輟學率出現某種意外時增加了一層額外的保護。

Very helpful. Thank you.

非常有幫助。謝謝。

Thanks, Gavin.

謝謝，加文。

Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.

謝謝。我們的下一個問題來自加拿大皇家銀行資本市場的布萊恩亞伯拉罕斯。您的線路已開通。

Hi everyone, this is Nevin on for Brian. Thank you for taking our questions.

大家好，我是 Nevin，代表 Brian 發言。感謝您回答我們的問題。

So, with the Voyage and Panorama studies underway, I was wondering if you could provide any more color on what you're seeing in the early rates of enrollment. Are they tracking in line with or better or worse than the prior phase 2 trial?

因此，隨著 Voyage 和 Panorama 研究的進行，我想知道您是否可以提供更多關於早期入學率的資訊。他們的追蹤結果是否與先前的第 2 階段試驗一致、更好或更差？

And then I guess among those who just given that, recent more enthusiasm for psychedelic clinical trials in general. Are you seeing similar types of patients enrolling in the GAD trial in the pivotal trials as you did in the phase 2, and I'm wondering if perhaps the increased awareness of psychedelics among patient population could change or potentially impact the expectancy bias among that group.

然後我想，在那些剛剛考慮到這一點的人中，最近人們對迷幻臨床試驗的熱情普遍更高了。您是否看到在關鍵試驗中參加 GAD 試驗的患者類型與在第 2 階段中相似，我想知道患者群體對迷幻藥的認識提高是否會改變或潛在影響該群體的預期偏差。

Yes, thanks so much, and so we can't provide a specific numbers enrollment is damaged, so we've been really highly encouraged by the enthusiasm from providers, from patients from the early enrollment trends, and are quite confident as a result in the progress we're making in both of the studies.

是的，非常感謝，因此我們無法提供具體的入學人數，因此，我們真的受到了來自供應商、來自早期入學趨勢的患者的熱情的鼓舞，並且對我們在這兩項研究中取得的進展非常有信心。

To your latter question, we wouldn't provide specifics on demographics, but the inclusion exclusion criteria and the population we're pursuing are very close to the identical, almost to the phase 2b trial. And so, certainly the expectation and all of the extensive screening that we do to ensure that we get the right patients in these studies, we feel quite confident that we're getting a similar population and, representative one. And on the final point, while we, certainly have seen growing interest, I think, I don't know that we could say that. That has had a direct impact in any measurable way on expectancy. I think population level or group level trends certainly are one thing, but I think you have to remember for an individual person, for a patient who's been suffering for GAD for in many cases, years or decades.

對於您的後一個問題，我們不會提供人口統計數據的具體信息，但納入排除標準和我們所追求的人群非常接近，幾乎與 2b 期試驗相同。因此，我們當然會期望並進行廣泛的篩檢，以確保我們在這些研究中獲得合適的患者，我們非常有信心我們會獲得相似的、代表性的人群。關於最後一點，雖然我們確實看到了人們日益增長的興趣，但我認為，我不知道我們是否可以這麼說。這對預期產生了可衡量的直接影響。我認為人口層級或群體層級的趨勢當然是一回事，但我認為你必須記住，對於個人來說，對於一個在許多情況下已經患有廣泛性焦慮症數年或數十年的患者來說，情況也是如此。

People enroll in latest stage trials with inevitable expectancy regardless of the treatment that they're being studied simply for the reason that most of those patients either are unsatisfied or are not getting the level of response from currently available therapies and therefore come into clinical trials with the hope that that something new will potentially help them. And so, while they may be randomized to get placebo or an inactive dose of drug in these studies, we certainly expect, like with any clinical trial, there's going to be a degree of expectancy, just by the nature of it being an experimental drug that we're studying.

無論研究的是哪種治療方法，人們都不可避免地會抱有期望參加最新階段的試驗，原因很簡單，大多數患者要么不滿意，要么沒有從現有的治療方法中獲得足夠的療效，因此他們參加臨床試驗，希望新的東西能夠潛在地幫助他們。因此，雖然在這些研究中他們可能會隨機接受安慰劑或非活性劑量的藥物，但我們當然期望，就像任何臨床試驗一樣，會有一定程度的期望，因為我們正在研究的是一種實驗藥物。

Okay, thank you. And then a quick follow up as well. I know you had mentioned that the inclusion exclusion criteria were similar across both panorama and voyage, but looking at the clinical trials listing for both of them, I see that the exclusion criteria for voyage specifically mentions bipolar disorder, but panorama does not. Is there any particular reason for that?

好的，謝謝。然後進行快速跟進。我知道您曾提到全景研究和航行研究的納入排除標準相似，但查看兩者的臨床試驗列表，我發現航行研究的排除標準特別提到了躁鬱症，而全景研究沒有。這其中有什麼特殊原因嗎？

No, the inclusion criteria consistent across both studies in that respect.

不，從這方面來看，兩項研究的納入標準是一致的。

Okay, thank you.

好的，謝謝。

Thank you. Our next question comes from Charles Duncan with Cantor Fitzgerald. Your line is open.

謝謝。我們的下一個問題來自 Cantor Fitzgerald 的 Charles Duncan。您的線路已開通。

Hey, morning, Rob and Dan. Congrats on the design and operationalizing this phase 3. Thanks for taking the question.

嘿，早安，羅布和丹。祝賀第三階段的設計與實施。感謝您回答這個問題。

I had another question about enrollment criteria. I think Dan mentioned that he expected, a broad swath of patients to be interested in the study, but I guess I'm wondering, are you seeing any, types of severity or treatment experience that are presenting and then with regard to experience with LSD or psychedelics in the past, what is happening in terms of the enrollment for the patients in Voyage and Panorama. Thanks.

我還有一個關於入學標準的問題。我認為丹提到過，他預計會有大批患者對這項研究感興趣，但我想知道，您是否看到了任何類型的嚴重程度或治療經驗，然後就過去使用 LSD 或迷幻藥的經驗而言，Voyage 和 Panorama 患者入組情況如何。謝謝。

Thanks Charles. I'll turn it over to Dan to answer both those.

謝謝查爾斯。我將把這兩個問題交給丹來回答。

Yes, consistent with what we believe to be a representative sample of people who seek treatment for GAD in general, what we're seeing, again, while we can't really comment on live enrollment in phase 3, what we were able to see in the phase 2 study again with like what Rob said, nearly identical inclusion exclusion was about 2/3 of patients with treatment experience who've been failed by prior treatments, about 1/3 who hadn't been treated, 10% to 15% with a fairly recent diagnosis of GAD. We know in the population that there are almost twice as many people walking around with symptoms of moderate to severe GAD who have never been diagnosed with it, on a population level, so when new treatments become available or new studies are launched, additional attention is paid to a diagnosis and obviously that diagnosis gets made in folks who have had the disease for some time.

是的，我們認為這是一個具有代表性的尋求 GAD 治療的人群樣本，我們再次看到，雖然我們無法真正評論第 3 階段的實時入組情況，但我們在第 2 階段的研究中再次看到，就像 Rob 所說的那樣，幾乎相同的納入排除標準是，約有 2/3 的患者在之前的治療中失敗了，約有 1/3 的患者在 10%的患者最近才被診斷出患有 GAD。我們知道，在人群中，有近兩倍的患有中度至重度廣泛性焦慮症但從未被診斷出患有這種疾病的人，因此，當新的治療方法出現或新的研究啟動時，人們會更加關注診斷，顯然，這種診斷是針對那些已經患病一段時間的人群做出的。

You'll recall in phase 2, we saw a mean [MA of 30], just about 30, so that puts people well into the severe category and there's no reason to think that we would particularly different in in this study. So, when we think about that, the breadth of the appeal of the treatment and the degree to which people aren't served by what's available, that's, again, while we can't comment exactly on phase three, there's no reason to think things would be looking all that different.

您會記得，在第 2 階段，我們看到了平均值 [MA 為 30]，大約是 30，因此這將人們完全歸入嚴重類別，並且沒有理由認為我們在這項研究中會特別不同。因此，當我們考慮到這一點時，考慮到這種治療方法的吸引力以及人們無法從現有治療方法中獲得幫助的程度，雖然我們無法對第三階段做出確切評論，但沒有理由認為情況會完全不同。

Okay. And then let me ask you a quick for a little bit of a nuance on panorama. I like that you're using a dose that doesn't appear effective to remove expectation bias, but or unblinding, excuse me.

好的。然後讓我快速問您一些有關全景的細微差別。我喜歡你使用一種看起來似乎無法有效消除期望偏差的劑量，但或解除盲法，對不起。

Were you surprised at how sharp the dose response curve was 50-microgram versus 100-microgram, and do you anticipate that 50-microgram really to have a no effect and to remove the fun or reduce the functional blindness?

您是否對 50 微克與 100 微克之間的劑量反應曲線如此之陡峭感到驚訝，您是否預計 50 微克真的不會產生影響並消除樂趣或減少功能性盲區？

Yes, thank, thanks so much for the question, Charles. I think it's two key features there, and I'll talk on the dose response aspect first, which is that certainly we, the design in the phase 2 study, the primary analysis was one that is aimed at defining a dose response where we pre-specified response curves and statistically showed that the data from the phase 2 study matched multiple of those candidate dose response curves. So, I'd say that that the data certainly matched the potential the assumptions we made going into the phase two study.

是的，非常感謝你提出這個問題，查爾斯。我認為它有兩個關鍵特徵，首先我將討論劑量反應方面，也就是說，我們在第二階段研究的設計中，主要分析旨在定義劑量反應，我們預先指定了反應曲線，並從統計上表明第二階段研究的數據與多個候選劑量反應曲線相匹配。所以，我想說，這些數據肯定符合我們進入第二階段研究時所做的潛在假設。

I think it was quite stark, as you mentioned, the fact that in the primary and phase two at week four, there was less than a point improvement over placebo at the 50-microgram level, and there was a 7.5, 7.6-unit improvement over placebo for the 100-microgram dose. So, while we weren't surprised by the overall shape of the curve, it is in quite a stark contrast that the difference in clinical response between 50-microgram and 100-microgram in the data that have been generated to date and if you recall, really the only data in the field to look at a comprehensive dose response across a full range. Now, on the second point, it's really important to express, and we think that the field in many instances has conflated some of the issues that are at play with why we take these additional methodological steps. So, we talked before about potential expectancy, which we certainly expect to be the case in any clinical trial.

我認為，正如您所提到的，事實是，在主要階段和第二階段的第四周，50 微克水平的療效比安慰劑改善不到一個點，而 100 微克劑量的療效比安慰劑改善了 7.5 到 7.6 個單位。因此，雖然我們對曲線的整體形狀並不感到驚訝，但迄今為止生成的數據中 50 微克和 100 微克之間的臨床反應差異卻形成了鮮明的對比，如果您還記得的話，這確實是該領域唯一可以查看全範圍內綜合劑量反應的數據。現在，關於第二點，表達確實很重要，我們認為該領域在許多情況下混淆了一些問題與我們採取這些額外方法步驟的原因。因此，我們之前談到了潛在預期，我們當然希望在任何臨床試驗中都存在這種情況。

And with any treatment, Universally the truth for psychiatric drugs, but for any treatment, where there is a clear discernible acute effect, there's the risk that functional activity could unbind the patients. And unbinding importantly is a binary variable. There's not a continuous degree. You can't be 20% unblinded or 80% unblinded, you're either blinded or not. And so, what we saw in the phase two data was that all patients across the dose levels effectively were unblinded. 88% or more across all those levels were functionally unblinded, yet we saw that stark dose response between the two levels and really the intent of including a 50-microgram dose is twofold. It's really important that that dose level is as close to the acute perceptual effects as the clinically active or the dose of interest that we're studying 100-microgram.

對於任何治療來說，精神藥物的治療都是普遍適用的，但對於任何治療來說，如果存在明顯可辨別的急性效應，則存在功能活動可能使患者失去控制的風險。解除綁定重要的是一個二元變數。沒有連續的學位。您不可能 20% 不盲，也不可能 80% 不盲，您要麼盲，要麼不盲。因此，我們在第二階段的數據中看到，所有劑量水平的患者實際上都沒有被盲化。所有這些水平中 88% 或更多的人在功能上都是非盲的，但我們看到兩個水平之間存在明顯的劑量反應，並且真正包含 50 微克劑量的意圖是雙重的。非常重要的是，該劑量水平應盡可能接近急性感知效應，例如臨床活性劑量或我們正在研究的感興趣的劑量 100 微克。

Otherwise, it doesn't have similar functional activity, and it doesn't really aid in the functional blinding that we're pursuing. But really what we're trying to do fundamentally is sever the tie between an expectancy bias and an impact on biasing the clinical outcomes. And we do that through many mechanisms, one of which is using line and centralized raids, but by having that dose, that that 50-microgram dose level, what we're able to do is effectively through the consent process inform patients that whether or not they feel an effect of the drug or acute perceptual effect on the day of dosing. They may be receiving a real dose of drug, or they may be receiving a dose that previously has been shown not to be clinically active. So, just because a patient assumes that they just because they feel something on a day of dosing, they can't assume that they're getting a dose of drug that's going to make them better and really that's as great of a length as any study has ever been asked to go in psychiatry to try to enhance the validity and minimize the bias of these outcomes because like with other approved GAD therapies like Xanax, for instance, there's a clear acute perceptual effect that just hasn't been looked at in the past. And so, we feel even stronger about the validity of the data that we'll be able to generate in these studies because of this additional analysis and the additional design unless we included in the phase 3 program.

否則，它就沒有類似的功能活動，而且它對我們所追求的功能盲化也沒有真正的幫助。但實際上，我們試圖從根本上切斷期望偏差與對臨床結果產生偏差的影響之間的關聯。我們透過多種機制來實現這一點，其中之一是使用線路和集中突襲，但透過該劑量，即 50 微克的劑量水平，我們能夠透過同意程序有效地告知患者他們是否在服藥當天感受到藥物的作用或急性感知作用。他們可能正在接受真實劑量的藥物，或者他們可能正在接受先前已證明不具有臨床活性的劑量。因此，不能僅僅因為患者認為他們在服藥當天感覺到了什麼就認為他們服用的藥物劑量會讓他們的情況好轉，這實際上已經達到了精神病學領域任何研究所要求的最高水平，旨在提高有效性並儘量減少這些結果的偏見，因為與其他已獲批准的 GAD 療法（例如 Xanax）一樣，存在明顯的急性感知效應，而這種效應在過去從未被研究過。因此，除非我們將其納入第 3 階段計劃，否則我們對在這些研究中能夠產生的數據的有效性更加有信心，因為有額外的分析和額外的設計。

It's that's helpful, Rob. One quick last question then going back to an earlier question, I think the ISI person asked regarding the adaptive design, what is the dropout rate that you are assuming could happen. So, that we can kind of gauge how it's going over the course of the trial.

這很有幫助，羅布。最後一個快速問題，然後回到先前的問題，我認為 ISI 人員詢問的是自適應設計，您假設可能發生的輟學率是多少。這樣，我們就可以判斷審判過程的進展。

And we've assumed the pool standard deviation of 10 units and a dropout rate of about 15%.

我們假設池標準差為 10 個單位，輟學率約為 15%。

Okay, thanks. Very helpful.

好的，謝謝。非常有幫助。

Thank you. Our next question comes from Francois Brisebois with Oppenheimer. Your line is open.

謝謝。我們的下一個問題來自 Oppenheimer 的 Francois Brisebois。您的線路已開通。

Hi, this is Dan on for Frank. Thanks for taking our question. Thanks for all the color around the enrollment as well as we think about the outcomes here. Just a quick one from us.

大家好，我是丹，代表弗蘭克。感謝您回答我們的問題。感謝您對招生的所有關注，我們也在考慮結果。我們只需簡單說一下。

Given all this, regulatory scrutiny in this space, is the upcoming, PTSD AdCom, is this something you're looking to learn from, to inform your own development, or is this the indications are different, so anything here? Thanks.

考慮到所有這些，該領域的監管審查即將到來，PTSD AdCom，這是您希望從中學習的東西，以指導您自己的發展，還是這些跡像有所不同，所以這裡有什麼？謝謝。

Yes, thanks so much, Dan. No, we're always looking at all the AdCom, particularly neuropsychopharmacology advisory committees just to understand the dynamics of those, but, given the difference in the population and in our development plans we certainly, are focused on execution of our studies and we we'll certainly be watching and observing but don't know that we see a direct impact on our program.

是的，非常感謝，丹。不，我們一直在關注所有的 AdCom，特別是神經精神藥理學諮詢委員會，以了解這些委員會的動態，但考慮到人口和發展計劃的差異，我們當然專注於研究的執行，我們肯定會觀察和觀察，但不知道這是否對我們的項目有直接影響。

Thank you.

謝謝。

Thank you. Our next question comes from Joel Beatty with Baird. Your line is open.

謝謝。我們的下一個問題來自貝爾德的喬爾·比蒂。您的線路已開通。

Hi, congrats on the progress and thanks for taking the question. The question is, and for the phase 3 trials in GAD, how much of a risk is there that some of those patients during the twelve week randomized phase go on to take another therapy, and then if that does happen, that it might happen more so in the placebo patients than the treatment patients, and then if that situation were to occur, how does that get handled by the stats plan?

您好，恭喜您取得進展，感謝您提出這個問題。問題是，對於 GAD 的 3 期試驗，在 12 週的隨機階段中，部分患者繼續接受其他療法的風險有多大？如果發生這種情況，安慰劑組患者比接受治療組患者發生這種情況的可能性更高？如果發生這種情況，統計計劃將如何處理？

Thank you.

謝謝。

Yes, thanks so much, Joel. We certainly have a high degree of confidence in our sights and go to great lengths to ensure that all patients adhere to the trial protocol, which includes, as a monotherapy includes taking no other therapies during the twelve-week randomized period and really throughout the duration of the study. So, we monitor that very closely and for patients who do violate that criterion. It is addressed in the statistical analysis plan. I don't know that we are prepared today to go through the specifics of that plan and have had great collaboration with FDA and development of our statical analysis plan for both of the phase 3 studies so.

是的，非常感謝，喬爾。我們對我們的觀點當然充滿信心，並竭盡全力確保所有患者遵守試驗方案，其中包括作為單一療法，在十二週的隨機期間以及整個研究期間不採取任何其他療法。因此，我們會密切監控違反該標準的患者。統計分析計劃中已對此進行了說明。我不知道我們今天是否準備好討論該計劃的具體內容，並且與 FDA 進行了良好的合作，並為兩個 3 期研究制定了靜態分析計劃。

But we certainly monitored very closely and try to ensure adherence to the protocol at every site and have had great success, historically and in our engagement with these site so far.

但我們確實進行了非常密切的監控，並試圖確保每個站點都遵守協議，並且從歷史上看以及迄今為止我們與這些站點的合作中都取得了巨大的成功。

Great, thank you.

太好了，謝謝。

Thank you. Our next question comes from Rudy Li with Chardan. Your line is open.

謝謝。我們的下一個問題來自 Chardan 的 Rudy Li。您的線路已開通。

Hi, thanks for taking my question. I have a question regarding the MDD indication. Given the competitive landscape for psychedelics, how important is MDD indication for MM120 to compete with, other psychedelic products? And when should we expect updates on the timing and the design of the second MDD study?

你好，謝謝你回答我的問題。我對 MDD 指示有疑問。鑑於迷幻藥的競爭格局，MDD 適應症對於 MM120 與其他迷幻藥產品的競爭有多重要？我們什麼時候可以得知第二次 MDD 研究的時間和設計的最新消息？

Thank you.

謝謝。

Yes, thanks so much, Rudy. Our overall, I think looking focusing on the overall development plan for MM120, we just see such a broad and massive market and opportunity to help potentially millions of patients, and having the broadest label certainly enables us to hopefully if the drug's approved market to that broader population, hopefully gain access and ensure that we can help as many of those patients as possible. So, When we think of psychiatry, we think of some of the major neurotic illness in psychiatry. Having a label that covers both GAD and MDD effectively means that a patient coming in the door with either cluster of symptoms would be on label candidate for the product and as we look around the landscape with many other therapies focus exclusively or primarily on treatment resistant depression.

是的，非常感謝，魯迪。總體而言，我認為，從 MM120 的整體開發計劃來看，我們看到瞭如此廣闊而龐大的市場和機會，可以幫助數百萬潛在的患者，而擁有最廣泛的標籤無疑使我們能夠希望如果該藥物獲得批准進入更廣泛的人群，我們希望能夠獲得併確保我們能夠幫助盡可能多的患者。因此，當我們想到精神病學時，我們會想到精神病學中的一些主要神經疾病。擁有有效涵蓋 GAD 和 MDD 的標籤意味著，出現任一症狀的患者都將成為該產品的候選對象，而我們環顧四周，許多其他療法只關注或主要關注難治性抑鬱症。

It's just a strategic difference in how we've approached the opportunity and what we think of in terms of the expansiveness of both the market and patient opportunity, how broad of an impact we can have. And that's informed everything from the selection of GAD where there's been so few therapies in the last twenty years, and overall there's far fewer treatments available for genetic anxiety disorder than for MDD, but also in our plans to go after these two, really significant and large populations, that would, in our view be able to set us apart and maximizing the patients we can help.

這只是我們在如何把握機會、如何看待市場和患者機會的廣闊性以及我們能夠產生多廣泛影響方面的策略差異。這不僅體現在對廣泛性焦慮症（GAD）的選擇上，因為過去二十年裡，這種疾病的治療方法很少，而且總體而言，治療遺傳性焦慮症的方法也比治療重度焦慮症（MDD）的方法少得多，而且我們計劃針對這兩個真正重要且龐大的群體，在我們看來，這將使我們脫穎而出，並最大限度地幫助患者。

Thank you. Our next question comes from Sumant Kulkarni with Cannacord Genuity. Your line is open.

謝謝。我們的下一個問題來自 Cannacord Genuity 的 Sumant Kulkarni。您的線路已開通。

Good morning. Nice to see the progress and thanks for taking my questions. I have two. The first one is, given you have breakthrough therapy designation for MM120 that potentially allows for more back and forth with the FDA, could you give us any details on when you had your last interaction with the agency and if any of the changes that are currently affecting government agencies have impacted your interactions in any way?

早安.很高興看到進展，並感謝您回答我的問題。我有兩個。第一個問題是，鑑於您擁有 MM120 的突破性療法認定，這可能讓您與 FDA 進行更多溝通，您能否向我們提供您上次與該機構互動的詳細信息，以及當前影響政府機構的任何變化是否以任何方式影響了你們的互動？

Yes, thank, thanks so much, Sumant. We, as you mentioned with breakthrough therapy designation, we do have frequent interactions with the agency and on various topics including the clinical Phase 3 program, but also clinical pharmacology and CMC and other aspects of the development program that are just as important to ensure the quality and the adequacy of our data support, submission, hopefully and approval.

是的，謝謝，非常感謝，Sumant。正如您所提到的突破性療法認定，我們確實與該機構就各種主題進行了頻繁的互動，包括臨床 3 期計劃、臨床藥理學和 CMC 以及開發計劃的其他方面，這些方面對於確保我們的數據支持、提交和批准的質量和充分性同樣重要。

We think very highly look at FDA as strong partners with us from the outset of our program, but especially as we've received the breakthrough therapy designation over the past year and brought on an incredible regulatory team who's just successfully interacted with the division extensively in the approval of [Coy Kaa] Therapeutics, so we've been really encouraged by the level of engagement and the thoughtfulness and the thoroughness with which the division and the agency more broadly have engaged with our program and you feel a high degree of alignment and consistency in our approach with the expectations that we're hearing, so we've been really encouraged and you know certainly there's been a lot of coverage of the disruption in Washington and all that's happening there fortunately at this stage our inter interactions with FDA have not been changed in any way and we've continued to watching the division psychiatry really go out of their way and go to great lengths to be constructive and highly engaged with us.

我們認為，從計畫一開始，FDA 就高度重視我們的強大合作夥伴，尤其是因為我們在過去一年中獲得了突破性療法認定，並組建了一支出色的監管團隊，該團隊剛剛在 [Coy Kaa] Therapeutics的批准過程中與該部門進行了廣泛的成功互動，因此，該部門和機構更廣泛地參與我們的項目，其參與程度、周到程度和徹底性讓我們深受鼓舞，您可以感覺到我們的方法與我們聽到的期望高度一致，因此我們深受鼓舞，而且您知道，關於華盛頓的混亂以及那裡發生的一切肯定是與 FDA 進行性報道，幸運的經歷，在這個階段，我們沒有與 FDA 互動性

Got it, thanks. And if we also, if we fast forward to a time when other psychedelic agents that involve shorter times in the clinic might become competitors at a time when MM120 is approved as well, what would the key point be in favor of MM120 versus a derate deuterated DMT, for example, with the knowledge that we haven't really seen phase two data on that molecule just yet.

明白了，謝謝。如果我們快轉到這樣一個時間點，即在 MM120 也獲得批准時，其他在臨床中需要更短時間的迷幻藥物可能會成為競爭對手，那麼，MM120 與降級氘代 DMT 相比，關鍵點是什麼呢？因為我們還沒有真正看到該分子的第二階段數據。

Look like, with 50 million patients that we might be able to treat with both the indications we're going after, there are more than enough patients for many new treatment modalities, but, some of the things we've been really encouraged by are both the magnitude and the durability in in large and well-controlled, well-conducted studies where we are exceeding a robust placebo by more than double the standard of care. That's not something we've seen broadly with the field and there's also in our market research, there's some site economics that play into this where a treatment that requires a high degree of patient throughput can be problematic for these sites of care.

看起來，我們可能能夠用我們正在追求的兩種適應症來治療 5000 萬名患者，對於許多新的治療方式來說，患者數量已經足夠多了，但是，真正讓我們感到鼓舞的是，在規模大、控制良好、實施良好的研究中，我們的治療水平比安慰劑高出一倍以上。這並不是我們在該領域廣泛看到的情況，而且在我們的市場研究中，也存在一些場地經濟因素，其中需要大量患者吞吐量的治療可能會對這些護理場地造成問題。

We look at clinics that delivers [bravado] and many of these clinics have to turn over the room four or five times a day, which they're being reimbursed on an hourly rate in many instances, that becomes a huge administrative burden and quite inefficient economically for these sites. So, I think at faith there have been some assumptions made about the duration of various products. We have been at every turn really encouraged and highly convicted about our approach and what that will mean for sites of care and for patient access.

我們看到，一些診所提供 [bravado] 服務，其中許多診所每天必須將房間週轉四五次，在很多情況下，他們是按小時收費的，這對這些診所來說是一個沉重的行政負擔，而且在經濟上效率很低。因此，我認為人們對於各種產品的持續時間已經做出了一些假設。我們始終對我們的方法以及這對護理站點和患者就診的意義感到非常鼓舞和堅信。

Thanks.

謝謝。

Thank you. As a reminder to ask a question, please press 11.

謝謝。提醒一下，提問時請按 11。

And our next question comes from Patrick Trucchio with HC Wainwright and Company. Your line is open.

我們的下一個問題來自 HC Wainwright and Company 的 Patrick Trucchio。您的線路已開通。

Thanks. Good morning. A couple of follow-up questions from me. So, clearly with the phase 3 trial and anxiety, primary endpoint is HAM-A. I'm just wondering which secondary endpoints, things like function or quality of life could be important from both a regulatory as well as a payer perspective.

謝謝。早安.我還有幾個後續問題。因此，顯然，對於第 3 階段試驗和焦慮，主要終點是 HAM-A。我只是想知道從監管和付款人的角度來看，哪些次要終點（例如功能或生活品質）可能很重要。

Secondly, I'm curious if you can discuss some of the HEOR, health economic outcome research that's been conducted and what further research that you plan to conduct in order to, further support MM120 after it's, potentially approved. And then just lastly, I think, the phase 2b trial I think showed an eight-point improvement on the HAM-A relative to placebo, I'm just curious how the learnings from that trial, kind of led to the powering for the phase 3 studies in GAD. But as well I'm wondering, I know that data was collected on the on the [madras] and how the learnings from the Phase 2b trial are influencing the phase 3 trial in MDD.

其次，我很好奇您是否可以討論一些已經進行的 HEOR、健康經濟結果研究，以及您計劃進行哪些進一步的研究，以便在 MM120 可能獲得批准後進一步支持它。最後，我認為 2b 期試驗表明，與安慰劑相比，HAM-A 提高了 8 個百分點，我只是好奇該試驗的經驗如何為 GAD 的 3 期研究提供動力。但我也想知道，我知道數據是在 [馬德拉斯] 收集的，以及 2b 期試驗的經驗如何影響 MDD 的 3 期試驗。

Yes, thanks so much, Patrick. So, to your first question.

是的，非常感謝，派崔克。那麼，對於你的第一個問題。

We're certainly looking at a number of additional secondary outcome measures in the phase 3 program. One that is of interest to us is CGI, which is, overall disease severity and patient functioning score. And so, that is one that we're quite interested in, and the time points we're interested in for the handmade the primary outcome measure.

我們當然正在研究第三階段計劃中的一些額外的次要結果指標。我們感興趣的是 CGI，即整體疾病嚴重程度和患者功能評分。因此，這是我們非常感興趣的，也是我們感興趣的手工製作主要結果測量的時間點。

In terms of the HEOR research, we, we've done extensive research, several of those studies which we've now presented posters and our dancing publications for. So, that covers everything from, I think when you look at GAD. There's been such a focus shift in the last twenty to thirty years away from anxiety, which for a long time was the predominant focus of psychiatry. There's been such a shift to major depressive disorder. We all remember, everyone worries, but depression is a chemical imbalance in your brain. These are commercials from the 1990s with the advent and introduction of SSRIs that led to a pretty massive diagnostic drift and for tools for depression being rolled out pretty substantially.

在 HEOR 研究方面，我們進行了廣泛的研究，其中幾項研究我們已經展示了海報和舞蹈出版物。所以，我認為，當你看 GAD 時，這涵蓋了一切。在過去的二三十年裡，人們的關注點已經從焦慮轉移到了別處，而焦慮在很長一段時間裡一直是精神病學研究的重點。已經出現了向重度憂鬱症的轉變。我們都記得，每個人都會擔心，但憂鬱症是大腦中的化學失衡。這些是 20 世紀 90 年代的廣告，隨著 SSRI 的出現和推出，診斷方法發生了相當大的變化，憂鬱症治療工具也得到了相當廣泛的推廣。

So, over that time, the burden and the prevalence of GAD has grown substantially and now affects as Dan mentioned, when we look at the broad epidemiological data and the research we've done, there's a significant portion of the population that is walking around with moderate or severe symptoms of generalized anxiety disorder that have never been diagnosed and presumably just think that's how life is, that's how human experiences. And so, a lot of our work so far has focused on that prevalence and also on the impact on quality of life and on economic parameters like workplace productivity, absenteeism, presenteeism, the overall economic burden on these patients, and, we have an incredible market access and to our team that is continuing this work and that that allows us to ultimately try to make arguments for the value of a product, and we really see that value come through overwhelmingly when we look at the magnitude of remission that we can achieve after a single administration that is durable for many months, the mass becomes really remarkably favorable in terms of the health economics for treatments such as this.

因此，在那段時間裡，GAD 的負擔和盛行率大幅增加，正如 Dan 所提到的那樣，當我們查看廣泛的流行病學數據和我們所做的研究時，我們發現相當一部分人口患有中度或重度廣泛性焦慮症的症狀，但從未得到診斷，大概他們只是認為生活就是這樣，人類的經歷就是這樣。因此，到目前為止，我們的許多工作都集中在這種患病率以及對生活品質和經濟參數的影響，例如工作場所生產力、曠工率、出勤率、這些患者的總體經濟負擔，而且，我們擁有令人難以置信的市場准入，我們的團隊正在繼續這項工作，這使我們能夠最終嘗試為產品的價值提出論據，當我們看到在一次持續數月的給藥後可以實現的緩解程度時，我們確實看到了這種價值的壓倒性體現，從此類治療的健康經濟學角度來看，質量確實非常有利。

On your last point, so, as you mentioned, 7.7-unit improvement over placebo for the 100-microgram dose in phase 2, and I think it's notable there that that was an improvement over about a fourteen-point placebo response, which is about around 40% larger than the historical average in GAD. So, most SSRI studies had a placebo response of about ten units.

關於最後一點，正如您所提到的，第 2 階段的 100 微克劑量比安慰劑提高了 7.7 個單位，我認為值得注意的是，這比大約 14 個點的安慰劑反應有所改善，比 GAD 的歷史平均值高出約 40%。因此，大多數 SSRI 研究的安慰劑反應約為十個單位。

Now we've assumed, as Dan mentioned, 90% power from power studied that 90% power based on a five-point improvement over placebo. I think that's a fairly conservative assumption, especially when you consider that the phase two study included five arms, four of which were a dose of active drug, and in the phase 3 studies we are doing a head to head or a three arm study where based on a broad body of research into the clinical trial methodologies, we would expect that to potentially reduce the placebo response. So, we've been quite conservative, and we also have the sample size re-estimation to make sure we don't lose that power in this study conduct. But certainly, feel quite confident in the strength of that powering and the probability of, having a successful study if we see a clinically meaningful response of a placebo.

現在我們假設，正如丹所提到的，90% 的功效來自於所研究的功效，而 90% 的功效是基於對安慰劑的五點改善。我認為這是一個相當保守的假設，特別是當你考慮到第二階段的研究包括五個組，其中四個是活性藥物的劑量，並且在第三階段的研究中，我們正在進行頭對頭或三組研究，基於對臨床試驗方法的廣泛研究，我們預計這可能會減少安慰劑反應。因此，我們一直非常保守，我們也重新估計了樣本量，以確保我們不會在這項研究中失去這種能力。但當然，如果我們看到安慰劑具有臨床意義的反應，我們對這種驅動力的強度和研究成功的可能性非常有信心。

Right, that's really helpful. And if I could just one additional question, just I'm wondering how you're measuring the long-term durability of MM120 and Part B of the studies, and do you need that data in order to be able to submit for approval or could you submit with the, I think the twelve-week data, would that be sufficient?

對，這真的很有幫助。我還有一個問題，我想知道您如何衡量 MM120 和研究 B 部分的長期耐久性，您是否需要這些數據才能提交審批，或者您是否可以提交，我認為十二週的數據，這樣就足夠了？

Yes, great question. I mean, we're not in a position today to speak to what would be acceptable for the application, but certainly if you look back at the historical precedents for depression and anxiety drugs.

是的，很好的問題。我的意思是，我們今天還不能談論什麼樣的申請才是可以接受的，但如果你回顧一下憂鬱症和焦慮症藥物的歷史先例，你肯定會明白的。

The outside of durability that's been required for almost all products has been, so then anxiety has been between four and twelve weeks of activity. So that that's quite encouraging that we have such a long and extensive precedence there. In terms of characterizing the durability response, we're looking at, beyond the twelve weeks and the nine-month extension period with the opportunity for open label treatment. So, a few things there. One is that until a patient and importantly, until a patient actually takes the open label product in that extension period, they're still blinded that they aren't told at the end of twelve weeks what treatment assignment, and we don't, at any point in the trial until everything is completely done, or we'd be unblinding on a per patient basis. Now, we can do, importantly, group level on blinding and primary analysis once we get through twelve weeks, because that has no impact on the study.

幾乎所有產品都要求外部耐用性，因此焦慮期在四到十二週之間。因此，我們在那裡擁有如此悠久和廣泛的先例，這是非常令人鼓舞的。在表徵耐久性反應方面，我們正在研究在十二週和九個月的延長期之後進行開放標籤治療的機會。所以，那裡有幾件事。一是，直到患者，重要的是，直到患者在延長期內實際服用開放標籤產品之前，他們仍然是盲人，在十二週結束時他們不會被告知治療任務是什麼，而且在試驗的任何時候，直到一切都完成之前，我們都不會告訴他們，否則我們將根據每個患者的情況揭開盲目的面紗。現在，重要的是，一旦我們過了十二週，我們就可以進行群體層面的盲法和初步分析，因為這對研究沒有影響。

But for patients who continue into the extension phase until they take open label drug, they remain blinded. And so, we could look at things like a capp Myer curve for the durability of response after a single treatment at baseline and presumably there will be a higher rate of relapse or inefficacy for patients who never respond in the placebo arm. And there is likely we would expect to be a longer period before an open label treatment is administered for patients who receive MM120 first before they versus placebo, at the first dose. And so, we're looking at a number of characteristics there both to quantify durability beyond twelve weeks after a single treatment and then the use patterns and the durability and subsequent response if patients do administer a label treatment in in the follow-up period.

但對於進入延長期直至服用開放標籤藥物的患者，他們仍然是盲法的。因此，我們可以透過諸如 Capp Myer 曲線之類的曲線來觀察基線單次治療後的反應持久性，並推測安慰劑組中從未產生反應的患者的復發率或無效率會更高。我們可能希望在對首次接受 MM120 治療的患者進行開放標籤治療之前，需要更長的時間，然後再接受安慰劑治療。因此，我們正在研究一些特徵，以量化單次治療後十二週以上的耐久性，然後研究使用模式以及患者在隨訪期間進行標籤治療時的耐久性和後續反應。

Great. Thanks so much.

偉大的。非常感謝。

Thank you. Our next question comes from Michael Okunewitch with Maxim Group. Your line is open.

謝謝。我們的下一個問題來自 Maxim Group 的 Michael Okunewitch。您的線路已開通。

Hey guys. Thank you so much for taking my questions today and congrats on all the progress we've made.

嘿，大家好。非常感謝您今天回答我的問題，並祝賀我們所取得的所有進展。

So, I guess just one quick question here on runway and capital use. You guys have done a fantastic job managing your balance sheet so far. You do have two phase 3s ongoing and a three launching in major depression, and the conventional wisdom there would suggest you would need a confirmatory study in MDD as well. So, would you expect a confirmatory and MDD to be launched concurrently with your other programs, and is this something you consider in your current runway projections?

所以，我想這裡只想問一個關於跑道和資本使用的簡單問題。到目前為止，你們在管理資產負債表方面做得非常出色。您確實有兩個正在進行的 3 期臨床試驗和一個針對重度憂鬱症的 3 期臨床試驗，而傳統觀點認為您還需要對 MDD 進行驗證性研究。那麼，您是否希望確認和 MDD 與您的其他項目同時啟動，這是您在當前跑道預測中考慮到的事情嗎？

Yes, thanks so much, Michael. We certainly, consider all of our development plans across all of our programs and our and our financial productions and guidance for cash and runway.

是的，非常感謝，邁克爾。當然，我們會考慮我們所有項目的所有發展計劃以及我們的財務產品和現金和跑道指導。

Our approach in major press disorder is such that, as we said, we're not in a position to comment on the exact precise timing or design of the second study in in MDD today. We have, had constructive progress in our overall planning for our program and our assets and certainly excited to share that data at a future point in time, and that that'll be informed by some of the progress in in our ongoing phase 3 studies and our regulatory interactions.

正如我們所說，我們在重大新聞障礙方面採取的方法是這樣的，我們無法評論今天在 MDD 中進行的第二項研究的確切時間或設計。我們在專案和資產的總體規劃方面取得了建設性進展，並且非常高興在未來某個時間點分享這些數據，這些數據將透過我們正在進行的第三階段研究和監管互動中的一些進展來提供資訊。

Certainly, one of the attributes in our execution of our program is the ability to contain, continue sites and efficiently. Keep them going in in terms of screening and enrollment. So, we're certainly, mindful of the operational efficiencies of when we start studies, but also, being financially prudent and responsible of how we're, managing our cash and our expenses over the conduct of our phase 3 program.

當然，我們執行計劃的屬性之一就是能夠有效地包含、繼續站點。讓他們繼續進行篩選和招生。因此，我們當然會注意開始研究時的營運效率，但同時也會在財務上保持審慎，並對我們如何在執行第三階段計劃時管理現金和費用負責。

All right. Thank you very much and once again, congrats on all the progress.

好的。非常感謝，並再次祝賀您取得的所有進展。

Thank you.

謝謝。

This concludes the question-and-answer session, and you may now disconnect.

問答環節到此結束，您可以斷開連線了。

Thank you for your participation, everyone, have a great day.

謝謝大家的參與，祝大家有個愉快的一天。