Mind Medicine (MindMed) Inc (MNMD) 2024 Q2 法說會逐字稿

Good morning, and welcome to the Mind Medicine second quarter 2024 financial results and corporate update conference call.

早上好，歡迎參加 Mind Medicine 2024 年第二季財務業績和公司更新電話會議。

(Operator Instructions) 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.

（操作員說明）本次電話會議正在 MindMed 網站 Mindmed.co 的投資者和媒體部分進行網路直播，電話會議結束後將提供錄音。

I would now like to introduce Rob Barrow, CEO of MindMed.

現在我想介紹一下 MindMed 執行長 Rob Barrow。

Please go ahead.

請繼續。

Thank you, and good morning, everyone.

謝謝大家，大家早安。

Welcome to our second quarter 2024 financial results and corporate update conference call.

歡迎參加我們的 2024 年第二季財務業績和公司更新電話會議。

Today, we will be sharing highlights from the second quarter along with the significant progress we've made with plans for our Phase 3 program in generalized anxiety disorder, or GAD.

今天，我們將分享第二季的亮點以及我們在廣泛性焦慮症（GAD）第三階段專案計劃中取得的重大進展。

Additionally, I'm excited to share further specifics about the expansion of our R&D program for MM120 into major depressive disorder or MDD, both of which are further supported by the financing we announced last week.

此外，我很高興與大家分享有關將 MM120 研發計劃擴展到重度憂鬱症或 MDD 的更多細節，這兩者都得到了我們上周宣布的融資的進一步支持。

The press release reporting our financial results and the presentation we will be using on today's call are both available in the investors and media section of our website, and our quarterly report on Form 10-Q for the quarter ended June 30, 2024, was filed this morning with the Securities and Exchange Commission.

報告我們財務業績的新聞稿以及我們將在今天的電話會議上使用的演示文稿均可在我們網站的投資者和媒體部分獲取，並且我們已提交截至2024 年6 月30 日的季度10-Q 表格季度報告今天早上與證券交易委員會。

During today's call and outlined on slide 2, 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.

在今天的電話會議中，我們將做出某些前瞻性聲明（如幻燈片2 所示），包括但不限於有關我們的產品候選者的潛在安全性、有效性、監管和臨床進展、我們預期的現金跑道以及我們的未來的聲明期望、計劃、夥伴關係和前景。

These statements are subject to various risks, such as changes in market conditions and difficulties associated with research and development and regulatory approval processes.

這些聲明面臨各種風險，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。

These and other risk factors are described in the filings made with the SEC, including our annual report on Form 10-K and our Form 10-Q filed today.

這些風險因素和其他風險因素在向 SEC 提交的文件中進行了描述，包括我們今天提交的 10-K 表格年度報告和 10-Q 表格。

Forward-looking statements are based on the assumptions, opinions, and estimates of management of 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, 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做出陳述之日的假設、意見和估計，包括未發生向 SEC 提交的文件中描述的風險和不確定性，或發生的其他重大事件MindMed 的正常業務範圍之外。

You are cautioned not to place undue reliance on these forward-looking statements, which are made as of today, August 13, 2024.

請您注意不要過度依賴這些截至 2024 年 8 月 13 日發布的前瞻性聲明。

MindMed disclaims any obligation to update such statements even if management's views change except as required by law.

即使管理階層的觀點發生變化，MindMed 也不承擔更新此類聲明的義務，除非法律要求。

Let me begin by taking you through today's agenda on slide 3.

首先，我將在投影片 3 上向您介紹今天的議程。

I'll start with our Q2 2024 business update and then Dr. Dan Karlin, our Chief Medical Officer will join to discuss our R&D plans for MM120 oral disintegrating tablet or ODT in GAD and MDD.

我將從 2024 年第二季的業務更新開始，然後我們的首席醫療官 Dan Karlin 博士將加入討論我們針對 GAD 和 MDD 的 MM120 口腔崩解片或 ODT 的研發計劃。

We are also pleased to be joined by Dr. Reid Robison, Senior Principal Investigator, Cedar Clinical Research and Adjunct Faculty at the University of Utah.

我們也很高興邀請猶他大學 Cedar 臨床研究和兼職教授資深首席研究員 Reid Robison 博士加入。

Dr. Robison is an investigator in our MM120 clinical development program and will provide his views on our Phase 3 clinical trials.

Robison 博士是我們 MM120 臨床開發計畫的研究員，他將就我們的 3 期臨床試驗發表意見。

Following Dr. Robison, I'll discuss our second quarter financial highlights, share our anticipated upcoming milestones, and then we'll conclude with the Q&A session where we will also be joined by Dr. Francois Lilienthal, our Chief Commercial Officer to answer your questions.

在 Robison 博士之後，我將討論我們第二季度的財務亮點，分享我們預期的即將到來的里程碑，然後我們將以問答環節結束，我們的首席商務官 Francois Lilienthal 博士也將加入其中，回答您的問題問題。

On slide 4, I'm pleased to share our progress for the quarter and for the first half of the year.

在投影片 4 上，我很高興分享我們本季和上半年的進度。

In June, we successfully completed a constructive end-of-phase 2 meeting with the US Food and Drug Administration, which supports the advancement of MM120 into pivotal Phase 3 clinical trials for GAD.

6 月，我們成功與美國食品藥物管理局舉行了建設性的第 2 階段結束會議，會議支持 MM120 進入 GAD 關鍵的第 3 階段臨床試驗。

We are on track to initiate our first Phase 3 trial for MM120 ODT in GAD in the second half of 2024, which marks a major milestone in our development program.

我們預計在 2024 年下半年在 GAD 啟動 MM120 ODT 的第一個 3 期試驗，這標誌著我們開發計畫的一個重要里程碑。

We are also excited to share with you our plans to expand our R&D program for MM120 into MDD, with the initiation of the Emerge Study, a registrational clinical trial for MM120 ODT and MDD, which we expect to be initiated in the first half of 2025.

我們也很高興與您分享我們計劃將 MM120 的研發計劃擴展到 MDD，並啟動 Emerge 研究，這是一項 MM120 ODT 和 MDD 的註冊臨床試驗，我們預計將於 2025 年上半年啟動。

We also expect to conduct a second registrational study in MDD with the study design and timing to be informed by the Emerge Study and additional regulatory discussions.

我們還期望在 MDD 中進行第二次註冊研究，研究設計和時間安排將由新興研究和其他監管討論提供資訊。

The scope and sequencing of our clinical program for MM120 and MDD is being carefully executed to balance the exciting opportunity represented by MDD, while maintaining a cash runway into 2027.

我們正在仔細執行 MM120 和 MDD 臨床計劃的範圍和順序，以平衡 MDD 所帶來的令人興奮的機遇，同時保持到 2027 年的現金跑道。

With this approach, we believe our cash runway will be sufficient to support operations for at least 12 months beyond our first Phase 3 readout in GAD.

透過這種方法，我們相信我們的現金跑道將足以支持我們在 GAD 的第一個第 3 階段讀數之後至少 12 個月的營運。

In June, we announced the US Patent and Trademark Office issued a new patent covering the formulation and manufacturing methods of MM120 ODT that extends our intellectual property protection for MM120 ODT through 2041, providing further runway for potential commercialization.

6 月，我們宣布美國專利商標局頒發了一項涵蓋 MM120 ODT 配方和製造方法的新專利，將我們對 MM120 ODT 的智慧財產權保護延長至 2041 年，為潛在的商業化提供了進一步的跑道。

We have also seen continued progress with our second lead program, MM402, which is our proprietary form of the R-enantiomer of MDMA.

我們也看到了我們的第二個主導專案 MM402 的持續進展，MM402 是我們 MDMA R 對映體的專有形式。

We are currently evaluating MM402 in a Phase 1 single ascending dose trial in healthy adults intended to characterize tolerability, pharmacokinetics, and pharmacodynamics.

我們目前正在健康成人中進行 1 期單劑量遞增試驗，以評估 MM402 的耐受性、藥物動力學和藥效學特徵。

We expect the results from this trial will enable further clinical trials to characterize the effects of repeated daily doses of MM402 and the exploration of early signs of efficacy in the Autism Spectrum Disorder population.

我們預計該試驗的結果將使進一步的臨床試驗能夠表徵每日重複劑量的 MM402 的效果，並探索自閉症譜系障礙族群的早期療效跡象。

Lastly, I'm pleased to report that we just completed a successful underwritten public offering, raising approximately $75 million in gross proceeds before deducting transaction fees and other offering related expenses.

最後，我很高興地向大家報告，我們剛剛成功完成了一次承銷公開發行，在扣除交易費用和其他發行相關費用之前籌集了約 7500 萬美元的總收益。

Based on our current operating plans, we believe that the proceeds from this offering, in addition to our cash and cash equivalents as of June 30, 2024, extends our cash runway into 2027 and at least 12 months beyond our first Phase 3 clinical readout in GAD.

根據我們目前的營運計劃，我們相信，除了截至2024 年6 月30 日的現金和現金等價物外，此次發行的收益還將我們的現金跑道延長至2027 年，並且比我們在2024 年的第一個3 期臨床結果至少延長12 個月。

Importantly, this funding demonstrates the continued enthusiasm towards our programs and strategy and allows us to rapidly advance MM120 in both GAD and MDD.

重要的是，這筆資金表明了我們對我們的計劃和策略的持續熱情，並使我們能夠在 GAD 和 MDD 方面快速推進 MM120。

Here on slide 5 is a look at our pipeline of three clinical stage programs, including our Phase 3 trials for MM120 in GAD and MDD.

第 5 張投影片展示了我們的三個臨床階段項目的流程，包括 MM120 在 GAD 和 MDD 的 3 期試驗。

As I mentioned, we remain on track to initiate the pivotal Phase 3 program for MM120 in GAD in the second half of 2024, and we intend to initiate the first registrational study in our newly announced MDD program in the first half of 2025.

正如我所提到的，我們仍有望在 2024 年下半年啟動 GAD 中 MM120 的關鍵 3 期項目，並打算在 2025 年上半年啟動我們新宣布的 MDD 項目中的第一項註冊研究。

As detailed on slide 6, MM120 has shown significant potential in addressing large unmet needs in brain health disorders.

正如幻燈片 6 所詳述的，MM120 在解決大腦健康疾病中大量未滿足的需求方面顯示出巨大的潛力。

Our Phase 2b trial for MM120 in GAD demonstrated an effect size more than double that of the standard of care and a 48% remission rate 12 weeks after a single dose.

我們針對 MM120 治療 GAD 的 2b 期試驗表明，單次給藥後 12 週的療效是標準治療的兩倍多，緩解率為 48%。

We also observed significant, rapid and durable effects on comorbid depression symptoms in GAD patients.

我們也觀察到對廣泛性焦慮症患者的共病憂鬱症狀有顯著、快速且持久的影響。

In the US alone, there are 20 million adults with GAD and 31 million adults with MDD.

光是在美國，就有 2,000 萬成年人患有 GAD，3,100 萬成年人患有 MDD。

Of these, 13 million and 18 million are treated annually for GAD and MDD, respectively.

其中，每年分別有 1,300 萬人和 1,800 萬人因 GAD 和 MDD 接受治療。

These two markets represent a substantial opportunity for effective treatments.

這兩個市場代表了有效治療的巨大機會。

We believe that, if approved, MM120 could offer patients a differentiating and compelling option in both GAD and MDD, which could position it to become a best-in-class treatment option targeting two of the biggest market opportunities in psychiatry.

我們相信，如果獲得批准，MM120 可以為 GAD 和 MDD 患者提供差異化且引人注目的選擇，這可能使其成為精神科兩個最大市場機會的一流治療選擇。

slide 7 outlines our overall program for MM120 in GAD and MDD, which incorporates constructive feedback from our recently completed end-of-phase 2 meeting with FDA.

投影片 7 概述了我們在 GAD 和 MDD 中的 MM120 總體計劃，其中納入了我們最近完成的與 FDA 的第 2 階段結束會議的建設性回饋。

In the coming quarters, we anticipate initiating three registrational studies across the GAD and MDD programs, including the Voyage and Panorama studies in GAD and the Emerge Study in MDD.

在接下來的幾個季度中，我們預計將在 GAD 和 MDD 專案中啟動三項註冊研究，包括 GAD 中的 Voyage 和 Panorama 研究以及 MDD 中的 Emerge 研究。

The initiation of pivotal studies for MM120 truly represents a major milestone for MindMed as we strive to become a leader in developing novel treatments to address brain health disorders.

MM120 關鍵研究的啟動確實代表了 MindMed 的一個重要里程碑，因為我們努力成為開發解決大腦健康疾病的新型療法的領導者。

Before turning the call over to Dan to go over the details and designs of our Phase 3 study, I want to take a minute to address our approach to some of the major topics that have come in focus since the FDA pharmacologic drug Advisory Committee meeting earlier this year and FDA's recent decision on Lykos Therapeutics application from MDMA assisted therapy for PTSD.

在將電話轉給 Dan 討論我們 3 期研究的細節和設計之前，我想花一點時間談談自 FDA 藥物諮詢委員會早些時候召開會議以來我們對一些主要主題的處理方法。 Therapeutics 申請MDMA 輔助治療PTSD。

Our development strategy outlined on slide 8, is rigorous and thoughtful and continuous to be appreciated by regulators, researchers, clinicians and research participants.

我們的發展策略如投影片 8 所示，嚴謹、深思熟慮，持續受到監管機構、研究人員、臨床醫生和研究參與者的讚賞。

We believe this will ultimately translate into confidence for patients and prescribers.

我們相信這最終將轉化為患者和處方醫生的信心。

Specifically, we have implemented several strategies to address key methodological considerations in this drug class, including the use of central raters blinded to both treatment assignment and visit number, the inclusion of expectancy and blinding questionnaires and perhaps most importantly, the elimination of psychotherapeutic intervention in our clinical trials.

具體來說，我們實施了幾種策略來解決該藥物類別中的關鍵方法學考慮因素，包括使用對治療分配和就診次數不知情的中央評估者、納入預期和盲法問卷，也許最重要的是，消除心理治療介入我們的臨床試驗。

Additionally, our approach to safety monitoring follows well established industry best practices in both through our Phase 3 clinical trials and dedicated clinical pharmacology trials, we intend to fully and robustly characterize the safety of MM120.

此外，我們的安全監測方法透過我們的 3 期臨床試驗和專門的臨床藥理學試驗都遵循既定的行業最佳實踐，我們打算全面、穩健地表徵 MM120 的安全性。

Our development of MM120 has been carefully designed to adhere to the highest clinical and ethical standards in alignment with FDA guidance.

我們對 MM120 的開發經過精心設計，符合 FDA 指導的最高臨床和道德標準。

We believe that our well-designed Phase 2b trial for MM120 and GAD demonstrated compelling tolerability and efficacy data that exceeds today's standard of care.

我們相信，我們精心設計的 MM120 和 GAD 2b 期試驗證明了令人信服的耐受性和療效數據，超越了當今的護理標準。

Additionally, we continue to publish scientific research backed by the robustness of our clinical data and our increasing body of evidence for MM120's potential as an emerging best-in-class product candidate, along with the growing unmet need to treat patients suffering from GAD, MDD and other brain health disorders.

此外，我們繼續發表以我們的臨床數據的穩健性和越來越多的證據支持的科學研究，證明MM120 作為新興的同類最佳候選產品的潛力，以及治療廣泛性焦慮症、重度憂鬱症患者日益成長的未滿足的需求和其他大腦健康障礙。

As we embark on our pivotal development programs for MM120, we remain both appreciative and excited by FDA's commitment to advancing research for the psychedelic drug class.

當我們開始 MM120 的關鍵開發計劃時，我們對 FDA 致力於推進迷幻藥類別的研究的承諾感到既感激又興奮。

This has been exemplified both through FDA's recent public statements in which they indicated that they continue to encourage research and drug development that will further innovation for psychedelic treatments.

FDA 最近的公開聲明證明了這一點，他們在聲明中表示，他們將繼續鼓勵研究和藥物開發，以進一步推動迷幻治療的創新。

In addition to the high degree of engagement and partnership. we have experienced in numerous interactions with the FDA over the course of the year.

除了高度的參與和夥伴關係之外。在這一年裡，我們與 FDA 進行了多次互動。

Now I'd like to turn the call over to Dr. Dan Karlin, our Chief Medical Officer to discuss our clinical development programs in detail.

現在我想將電話轉給我們的首席醫療官 Dan Karlin 博士，詳細討論我們的臨床開發計劃。

Dan?

擔？

Thank you, Rob.

謝謝你，羅布。

Turning to slide 10.

轉到投影片 10。

We believe MM120 has the potential to address large unmet needs in major brain health disorders, based on the compelling results we shared from our Phase 2 trial for MM120 in GAD.

基於我們在 MM120 治療廣泛性焦慮症的 2 期試驗中分享的令人信服的結果，我們相信 MM120 有潛力解決主要大腦健康疾病中大量未滿足的需求。

In this trial, we observed a rapid onset of effect with a 1.8-point reduction in clinical global impression severity or CGI-S, within 24 hours in participants treated with 100 micrograms, which was highly statistically significant, with a p-value less than 0.0001.

在這項試驗中，我們觀察到，接受100 微克劑量治療的參與者在24 小時內觀察到效果迅速起效，臨床整體印象嚴重程度或CGI-S 降低了1.8 分，具有高度統計顯著性， p 值小於0.0001。

The response was durable, showing a 21.9-point improvement in the Hamilton Anxiety Scale, or HAM-A, at week 12 in participants treated with 100 micrograms.

該反應是持久的，在第 12 週時，接受 100 微克治療的參與者的漢密爾頓焦慮量表 (HAM-A) 改善了 21.9 分。

This further improvement from week four indicates potential long-lasting effects.

從第四週開始的進一步改善顯示了潛在的長期影響。

Importantly, the magnitude of response in participants given MM120 was such that 48% of participants who received from 100 micrograms remained in remission at week 12.

重要的是，接受 MM120 治療的參與者的反應程度如此之大，接受 100 微克治療的參與者中有 48% 在第 12 週仍處於緩解狀態。

This high remission rate is particularly encouraging for a chronic condition like GAD.

對於像廣泛性焦慮症這樣的慢性疾病來說，這種高緩解率尤其令人鼓舞。

The treatment also demonstrated a favorable safety and tolerability profile, with most adverse events limited to the dosing day, which is crucial for patient acceptance and adherence.

該治療還表現出良好的安全性和耐受性，大多數不良事件僅限於給藥日，這對於患者的接受度和依從性至關重要。

Finally, these results were achieved with no additional therapy, highlighting the potential for MM120 as a standalone treatment for GAD.

最後，這些結果是在沒有額外治療的情況下獲得的，凸顯了 MM120 作為廣泛性焦慮症獨立治療的潛力。

These outcomes support our Phase 3 program in GAD.

這些成果支持我們的 GAD 第三階段計畫。

I'll now discuss our Phase 3 development plan for MM120 in GAD on slide 11.

我現在將在投影片 11 上討論 GAD 中 MM120 的第 3 階段開發計畫。

As Rob mentioned, in June, we completed a highly collaborative and constructive end-of-phase 2 meeting with FDA, reaching alignment on our Phase 3 pivotal trials.

正如 Rob 所提到的，在六月份，我們與 FDA 完成了一次高度合作和建設性的第二階段結束會議，在我們的第三階段關鍵試驗上達成了一致。

This program will consist of two pivotal clinical trials, the Voyage study and the Panorama study.

該計劃將包括兩項關鍵臨床試驗：Voyage 研究和 Panorama 研究。

Each trial consists of two parts.

每個試驗由兩部分組成。

Part A will be a 12 week, randomized, double-blind, placebo controlled, parallel group study assessing the efficacy and safety of MM120 ODT versus placebo.

A 部分將是一項為期 12 週的隨機、雙盲、安慰劑對照、平行組研究，評估 MM120 ODT 與安慰劑相比的有效性和安全性。

Part B of each trial will be an open label, 40-week extension study designed to provide important long-term data on the durability and potential retreatment profile for MM120.

每個試驗的 B 部分將是一項開放標籤、為期 40 週的擴展研究，旨在提供有關 MM120 的耐久性和潛在再治療概況的重要長期數據。

Voyage is anticipated to enroll approximately 200 participants who will be randomized 1:1 to receive MM120 ODT 100 micrograms or placebo.

Voyage 預計將招募約 200 名參與者，他們將按照 1:1 的比例隨機分配接受 MM120 ODT 100 微克或安慰劑。

Panorama is anticipated to enroll approximately 240 participants who will be randomized 5:2:5 to receive MM120 ODT 100 micrograms, MM120 ODT 50 micrograms or placebo.

Panorama 預計將招募約 240 名參與者，他們將按照 5:2:5 的比例隨機分配接受 MM120 ODT 100 微克、MM120 ODT 50 微克或安慰劑。

In accordance with FDA guidance and our regulatory discussions to date, our clinical program for MM120 continues to utilize complimentary study designs across our Phase 2 and 3 studies to address key methodological issues such as functional and blinding.

根據 FDA 指導和我們迄今為止的監管討論，我們的 MM120 臨床計劃繼續在我們的 2 期和 3 期研究中利用免費研究設計來解決關鍵的方法學問題，例如功能和盲法。

In this regard, in the Panorama study, we are including a 50-microgram arm to confound participants ability to accurately assess the dose condition to which they have been randomized.

在這方面，在全景研究中，我們加入了一個 50 微克的劑量組，以混淆參與者準確評估他們被隨機分配的劑量條件的能力。

We believe that this approach builds on the evidence from our Phase 2b study in which we demonstrated that, despite functional and blinding, all tested doses of MM120, the lower doses, 25 micrograms and 50 micrograms, did not demonstrate a meaningful clinical response, supporting our view that the anxiolytic response to MM120 is independent of functional unblinding.

我們相信，這種方法建立在我們2b 期研究的證據之上，在該研究中，我們證明，儘管具有功能性和致盲性，但所有測試的MM120 劑量（較低劑量，25 微克和50 微克）並未表現出有意義的臨床反應，支持我們認為對 MM120 的抗焦慮反應與功能揭盲無關。

While we previously observed and almost 8-point improvement for MM120 over placebo at week 12, both Voyage and Panorama have been designed to have 90% power to detect a 5-point improvement over placebo based on certain statistical assumptions.

雖然我們之前觀察到MM120 在第12 週時比安慰劑有近8 點的改善，但基於某些統計假設，Voyage 和Panorama 都被設計為有90% 的功效檢測到比安慰劑有5 點的改善。

Additionally, in both studies, we will use an adaptive design with an interim blinded sample size re-estimation, which allows for an increase in sample size of up to 50% in each study.

此外，在這兩項研究中，我們將使用自適應設計和臨時盲態樣本量重新估計，這使得每項研究的樣本量增加最多 50%。

This approach allows us to adjust for variability in nuisance parameters with the goal of maintaining statistical power and enhancing the interpretability of our results.

這種方法使我們能夠調整幹擾參數的變異性，以保持統計功效並增強結果的可解釋性。

Key elements such as inclusion and exclusion criteria will largely mirror our successful Phase 2b trial in GAD and both Phase 3 studies will recruit adults aged 18 to 74 with a diagnosis of GAD and a HAM-A score of 20 or greater.

納入和排除標準等關鍵要素將在很大程度上反映我們成功的GAD 2b 期試驗，兩項3 期研究將招募年齡在18 至74 歲之間、診斷為GAD 且HAM-A 評分為20 或更高的成年人。

During Part B of the Phase 3 studies, investigators will closely monitor patients using electronic patient reported outcomes, central rater-assessed HAM-A, and clinician administered scales.

在第 3 階段研究的 B 部分期間，研究人員將使用電子病患報告結果、中央評估者評估的 HAM-A 和臨床醫生管理量表密切監測病患。

Participants will be eligible for retreatment with MM120 ODT 100 micrograms if their HAM-A score reaches 16 or higher, with up to four treatments available through Part B.

如果參與者的 HAM-A 分數達到 16 或更高，則他們將有資格接受 MM120 ODT 100 微克的再治療，透過 B 部分最多可獲得四次治療。

Importantly, the design allows an assessment of the durability of the treatment effect, the need for and response to retreatment, and long-term safety.

重要的是，該設計可以評估治療效果的持久性、再治療的需求和反應以及長期安全性。

Key outcomes from Part B will include time to retreatment or inefficacy.

B 部分的主要結果將包括再治療或無效的時間。

We will also assess safety data on repeated treatments, average treatments per year, and response to retreatment.

我們還將評估重複治療、每年平均治療以及對再治療的反應的安全性數據。

This information will be valuable in understanding the longer-term dynamics of MM120 ODT treatment in GAD patients.

這些資訊對於了解 MM120 ODT 治療 GAD 患者的長期動態非常有價值。

Overall, both Voyage and Panorama are designed to be consistent with our successful Phase 2b trial, including using the HAM-A as our primary outcome measure, with the primary endpoint for the Phase 3 programs being changed from baseline to week 12, which is consistent with the durability we observed in Phase 2.

總體而言，Voyage 和Panorama 的設計都與我們成功的2b 期試驗保持一致，包括使用HAM-A 作為我們的主要結局指標，而3 期項目的主要終點從基線更改為第12 週，這是一致的與我們在第二階段觀察到的耐用性。

Based on the data we collected in Phase 2, we have also agreed with FDA to a reduction in treatment session duration from a minimum of 12 hours to 8 hours.

根據我們在第 2 階段收集的數據，我們也與 FDA 達成一致，將治療持續時間從至少 12 小時減少到 8 小時。

This is operationally advantageous in our research program and enhances MM120's practicality in real world settings.

這在我們的研究項目中具有操作優勢，並增強了 MM120 在現實環境中的實用性。

We will continue to collect data on monitoring times and safe parameters for determining the appropriate timing for ending sessions using structured, intentionally designed criteria to determine the time, course, and resolution of drug effects that could require monitoring.

我們將繼續收集有關監測時間和安全參數的數據，以確定結束療程的適當時間，使用結構化的、有意設計的標準來確定可能需要監測的藥物效應的時間、過程和解決方案。

We are happy to say that we remain on track and expect to initiate our first Phase 3 trial, Voyage, in GAD this year.

我們很高興地說，我們仍處於正軌，並預計今年在 GAD 啟動我們的第一個 3 期試驗 Voyage。

Turning to slide 12.

轉到投影片 12。

As Rob stated earlier, we are also excited to announce the expansion of our R&D program for MM120 into MDD.

正如 Rob 之前所說，我們也很高興地宣布將 MM120 的研發計畫擴展到 MDD。

Data from our Phase 2 GAD study led to our decision to pursue MDD as an additional indication for MM120, given the demonstrated potential for antidepressant effects.

鑑於已證明的抗憂鬱作用潛力，我們 2 期 GAD 研究的數據促使我們決定將 MDD 作為 MM120 的額外適應症。

In the 100-microgram dose group, we observed an 18.7-point improvement from baseline in the Montgomery-Asberg depression rating scale or MADRS score at week 12.

在 100 微克劑量組中，我們觀察到第 12 週時 Montgomery-Asberg 憂鬱評定量表或 MADRS 評分較基線提高了 18.7 分。

This represented a 6.4-point advantage over placebo, which was statistically significant with a p-value less than 0.01. These results are particularly encouraging given that the study wasn't powered for this endpoint and that baseline MADRS scores were lower than we would expect in patients experiencing a major depressive episode, which appeared to create a sealing effect on the response to MM120.

這比安慰劑有 6.4 點的優勢，安慰劑的 P 值小於 0.01，具有統計顯著性。這些結果特別令人鼓舞，因為研究沒有針對這一終點，而且基線 MADRS 評分低於我們對經歷重度憂鬱發作的患者的預期，這似乎對 MM120 的反應產生了封閉效應。

Slide 13 represents the Phase 3 development program for MM120 and MDD, which we expect will consist of two pivotal clinical trials.

投影片 13 展示了 MM120 和 MDD 的 3 期開發計劃，我們預計該計劃將包括兩項關鍵的臨床試驗。

Our first trial the Emerge Study, like our pivotal trials in GAD, will be comprised of two parts, Part A, which is a 12 week, randomized, double-blind, placebo controlled, parallel group study assessing the efficacy and safety of a single dose of MM120 ODT versus placebo.

我們的第一項試驗Emerge 研究，就像我們在GAD 中的關鍵試驗一樣，將由兩部分組成，A 部分是一項為期12 週的隨機、雙盲、安慰劑對照、平行組研究，評估單一藥物的有效性和安全性。

And Part B, which is a 40 week extension study during which participants will be eligible for open label treatment with MM120 ODT subject to certain conditions for retreatment eligibility.

B 部分是一項為期 40 週的延伸研究，在此期間，參與者將有資格接受 MM120 ODT 的開放標籤治療，但須符合某些再治療資格條件。

Emerge is anticipated to enroll at least 140 participants, randomized 1:1 to receive MM120 ODT 100 micrograms or placebo.

Emerge 預計將招募至少 140 名參與者，以 1:1 的比例隨機分配接受 MM120 ODT 100 微克或安慰劑。

The primary endpoint in Emerge will be the change from baseline in MADRS score at week six between MM120 ODT 100 micrograms and placebo.

Emerge 的主要終點是 MM120 ODT 100 微克和安慰劑之間第六週 MADRS 評分相對於基線的變化。

We expect to conduct a second registrational trial in MDD in the future with the design and timing to be informed by the Emerge Study and additional regulatory discussions.

我們預計未來將在 MDD 中進行第二次註冊試驗，其設計和時間安排將由 Emerge 研究和其他監管討論提供資訊。

As Rob mentioned earlier, our planned execution of the MM120 program and MDD will balance this exciting opportunity across two pivotal programs with our continued operational and financial diligence.

正如 Rob 之前提到的，我們計劃執行的 MM120 計劃和 MDD 將在兩個關鍵計劃中平衡這一令人興奮的機會與我們持續的營運和財務調查。

With that, I am happy to introduce Dr. Reid Robison, who will provide his perspective on our Phase 3 trials.

至此，我很高興向大家介紹 Reid Robison 博士，他將就我們的第三階段試驗提供他的觀點。

Thanks Dan.

謝謝丹。

I'm very excited about the Phase 3 development programs that you just shared as I believe they stand to make a significant impact in the field of psychiatry.

我對您剛剛分享的第三階段開發計劃感到非常興奮，因為我相信它們將對精神病學領域產生重大影響。

I've been personally thrilled with the results I've seen so far from MindMed's MM120 development program, the GAD Phase 2b results are truly impressive, with MM120 exhibiting rapid and robust efficacy sustained 12 weeks after a single dose.

我個人對 MindMed 的 MM120 開發計劃迄今為止看到的結果感到非常興奮，GAD 2b 期結果確實令人印象深刻，MM120 在單劑量後持續 12 週，表現出快速而強大的療效。

Equally impressive is the change in MADRS score from baseline to week 12 in the Phase 2b GAD trial, participants showing improvement in comorbid depressive symptoms.

同樣令人印象深刻的是 2b 期 GAD 試驗中 MADRS 評分從基線到第 12 週的變化，參與者的共病憂鬱症狀有所改善。

For people suffering from GAD, including with comorbid depression, these trials offer a beacon of hope, and I've seen firsthand how debilitating both conditions are severely impacting quality of life.

對於患有廣泛性焦慮症（包括合併憂鬱症）的人來說，這些試驗提供了希望的燈塔，我親眼目睹了這兩種疾病如何嚴重影響生活品質。

Given that current standards of care are falling short of meeting our patient’s needs, it is vital that we develop and bring to market new, effective treatment options.

鑑於目前的護理標準無法滿足患者的需求，我們開發並向市場推出新的有效治療方案至關重要。

Three things stand out about the Phase 3 development programs that are important from an investigator and physician perspective that I want to share with you today.

從研究者和醫生的角度來看，第三階段開發計畫的三件事很重要，我今天想與大家分享。

First, the Phase 3 programs are operationally efficient.

首先，第三階段計劃運作有效率。

Second, they enhance our ability to recruit patients.

其次，它們增強了我們招募患者的能力。

And third, the Phase 2 and 3 trials are similar in design, suggesting a high degree of read through as possible.

第三，第二階段和第三階段試驗的設計相似，顯示盡可能高度通讀。

All of this will make our execution of these trials more seamless.

所有這些都將使我們的試驗執行更加順利。

I'll break all three attributes down further.

我將進一步分解這三個屬性。

From an operational perspective, the key design elements of both Phase 3 programs make them efficient to run.

從營運角度來看，這兩個第三階段專案的關鍵設計元素使它們能夠有效運作。

This operational ease is crucial as it allows my team to manage the trials effectively while maintaining scientific rigor.

這種操作簡便性至關重要，因為它使我的團隊能夠有效管理試驗，同時保持科學嚴謹性。

In the GAD trials, reducing treatment session monitoring from 12 to 8 hours is an example of this, making delivery of MM120 more practically feasible, mirroring how I would expect to treat patients if MM120 is approved.

在 GAD 試驗中，將治療療程監測從 12 小時減少到 8 小時就是一個例子，這使得 MM120 的交付更加切實可行，這反映瞭如果 MM120 獲得批准，我預計如何治療患者。

Another significant advantage of these trials is our ability to efficiently recruit and enroll patients.

這些試驗的另一個顯著優勢是我們能夠有效地招募和入組患者。

While the GAD program will start earlier than the MDD program, having both programs run concurrently, we can tailor recruitment efforts to match specific diagnosis.

雖然 GAD 計劃將早於 MDD 計劃啟動，但透過同時運行這兩個計劃，我們可以調整招募工作以匹配特定的診斷。

GAD and MDD have overlapping symptoms, and this approach improves our ability to put patients in whichever program is appropriate for their clinical presentation, thereby accelerating enrollment.

GAD 和 MDD 具有重疊的症狀，這種方法提高了我們將患者納入適合其臨床表現的計劃的能力，從而加快了入組速度。

Lastly, the design of these trials directly builds on MindMed's Phase 2b GAD trial results.

最後，這些試驗的設計直接基於 MindMed 的 2b 期 GAD 試驗結果。

This continuity enables us to build on existing data, enhancing the ability to validate prior findings and the efficacy and safety of MM120 ODT with a high degree of consistency.

這種連續性使我們能夠以現有資料為基礎，增強驗證先前發現以及高度一致性的 MM120 ODT 有效性和安全性的能力。

In addition, the 12 week primary endpoint for the Phase 3 trials in GAD should provide evidence on durability, which I believe is of utmost importance to physicians and patients.

此外，GAD 3 期試驗的 12 週主要終點應該提供持久性的證據，我認為這對醫生和患者來說至關重要。

I'm looking forward to getting these Phase 3 trials started.

我期待著這些第三階段試驗的開始。

They have the potential to pave the way for significant advancements in treating GAD and MDD, and I'm eager to see the results for MindMed can move forward with the development of MM120 and make a meaningful impact on patient’s lives.

它們有潛力為治療 GAD 和 MDD 的重大進展鋪平道路，我渴望看到 MindMed 的結果能夠隨著 MM120 的開發而向前發展，並對患者的生活產生有意義的影響。

And with that, I'll turn the call back over to Rob.

然後，我會將電話轉回給 Rob。

Thank you, Dr. Robison.

謝謝你，羅賓遜醫生。

We're excited to get started and grateful to be aligned on our pivotal programs with clinicians like you.

我們很高興能夠開始，並感謝與像您這樣的臨床醫生在我們的關鍵項目上保持一致。

I'll now turn to our financial results for the quarter ended June 30, 2024, which are highlighted on slide 15.

我現在將討論截至 2024 年 6 月 30 日的季度的財務業績，幻燈片 15 中重點介紹了這些業績。

As of June 30, 2024, the company had cash and cash equivalents totaling $243.1 million, compared to $99.7 million as of December 31, 2023.

截至2024年6月30日，該公司的現金及現金等價物總額為2.431億美元，截至2023年12月31日為9,970萬美元。

We believe that our cash and cash equivalents as of June 30, 2024, combined with the proceeds from our recently closed financing will be sufficient to fund our operations into 2027.

我們相信，截至 2024 年 6 月 30 日，我們的現金和現金等價物，加上我們最近完成的融資的收益，將足以為我們到 2027 年的營運提供資金。

Based on our current operating plan and anticipated R&D milestones, we expect this cash runway to extend at least 12 months beyond the top line data readout for our first Phase 3 trial of MM120 in GAD.

根據我們目前的營運計畫和預期的研發里程碑，我們預計這條現金跑道將比我們在 GAD 中 MM120 的第一個 3 期試驗的頂線數據延長至少 12 個月。

For the six months ended June 30, 2024, net cash used in operating activities was $36.6 million, compared to $27.2 million for the same period in 2023.

截至2024年6月30日的六個月，經營活動使用的現金淨額為3,660萬美元，而2023年同期為2,720萬美元。

Research and development expenses were $14.7 million for the quarter ended June 30, 2024, compared to $14.8 million for the same period in 2023, representing a decrease of $0.1 million.

截至 2024 年 6 月 30 日的季度，研發費用為 1,470 萬美元，較 2023 年同期的 1,480 萬美元減少 10 萬美元。

The decrease is primarily due to decreases of $0.5 million in expenses related to our MM120 GAD program and a decrease of $2 million in expenses related to preclinical activities, partially offset by an increase of $1 million in internal personnel costs as a result of increasing research and development capacity and an increase of $1.4 million in expenses related to our MM402 program.

這一減少主要是由於與MM120 GAD 項目相關的費用減少了50 萬美元，以及與臨床前活動相關的費用減少了200 萬美元，但由於研究和研究的增加而導致內部人員成本增加了100 萬美元，部分抵消了這一減少。

We do anticipate R&D expenses to ramp up in the second half of this year and in 2025 as we get the Phase 3 studies in GAD and MDD up and running.

我們預計，隨著 GAD 和 MDD 第三階段研究的啟動和運行，研發費用將在今年下半年和 2025 年增加。

General and administrative expenses were $9.8 million for the quarter ended June 30, 2024, compared to $14.4 million for the same period in 2023, a decrease of $4.6 million.

截至 2024 年 6 月 30 日的季度，一般及管理費用為 980 萬美元，較 2023 年同期的 1,440 萬美元減少了 460 萬美元。

The decrease was primarily attributable to professional services fees and expenses during the three month into June 30, 2023 relating to the proxy contest in connection with our 2023 annual general meeting of shareholders, partially offset by increased stock-based compensation expense.

減少的主要原因是截至 2023 年 6 月 30 日的三個月內與我們 2023 年年度股東大會相關的代理權爭奪相關的專業服務費用和支出，部分被股票補償費用的增加所抵消。

The company's net loss for the quarter ended June 30, 2024, was $5.9 million, compared to $29.1 million for the same period in 2023.

該公司截至 2024 年 6 月 30 日的季度淨虧損為 590 萬美元，而 2023 年同期為 2,910 萬美元。

The decrease was primarily due to changes in the fair value of 2022 US dollar financing warrants of $15 million.

減少的主因是2022年美元融資認股權證公允價值變動1,500萬美元。

This is an exciting time for us at MindMed with many key catalysts coming up over the next couple of years, as you can see highlighted on Slide 16.

對於 MindMed 來說，這是一個激動人心的時刻，未來幾年將出現許多關鍵催化劑，正如幻燈片 16 中突出顯示的那樣。

We anticipate initiating Voyage, our first Phase 3 trial in GAD in second half of 2024 and Panorama, our second Phase 3 trial in GAD in the first half of 2025.

我們預計將於 2024 年下半年啟動 Voyage（我們在 GAD 的第一個 3 期試驗）和 Panorama（我們在 2025 年上半年在 GAD 中的第二個 3 期試驗）。

We also expect to initiate Emerge, our first Phase 3 clinical trial in MDD into the first half of 2025.

我們也預計在 2025 年上半年啟動 Emerge，這是我們針對 MDD 的第一個 3 期臨床試驗。

We're projecting top line part A readouts for these pivotal trials starting with Voyage in the first half of 2026 and then Panorama and Emerge in the second half of 2026.

我們預計這些關鍵試驗的 A 部分頂線讀數將從 2026 年上半年的 Voyage 開始，然後是 2026 年下半年的 Panorama 和 Emerge。

These anticipated milestones represent significant value inflection points for our company and could potentially bring us closer to providing novel and highly differentiated treatment options for patients with GAD and MDD.

這些預期的里程碑代表了我們公司的重要價值轉折點，並可能使我們更接近為廣泛性焦慮症和重度憂鬱症患者提供新穎且高度差異化的治療選擇。

We believe that the evidence generated to date on MM120 validates our scientific understanding of MM120s mechanism of action and shows the potential for an emerging best-in-class product profile compared to today's standards of care.

我們相信，迄今為止在 MM120 上產生的證據驗證了我們對 MM120 作用機制的科學理解，並顯示了與當今的護理標準相比，新興的一流產品概況的潛力。

We are excited to advance our pipeline and to be on the cusp of moving forward with our pivotal development programs for MM120 in both GAD and MDD.

我們很高興能夠推進我們的產品線，並處於 GAD 和 MDD 中推進 MM120 關鍵開發計劃的風口浪尖。

With strong market protection and IP strategies and a cash runway into 2027 and 12 months beyond our first Phase 3 readout, we are well positioned to execute on our strategy.

憑藉強大的市場保護和智慧財產權策略，以及到 2027 年以及距離我們第一個第 3 階段的公佈後 12 個月的現金跑道，我們有能力執行我們的策略。

As we conclude, I want to extend my sincere appreciation and gratitude for the critical work and careful execution that has brought MindMed ever closer to realizing our mission.

最後，我想對 MindMed 所做的關鍵工作和認真執行表示誠摯的讚賞和感謝，正是這些工作和認真的執行使 MindMed 更加接近實現我們的使命。

I would like to thank our highly talented and deeply committed team, our research collaborators and clinical investigator teams, our investors and the many other individuals who have been supportive, especially our patients and their families.

我要感謝我們才華橫溢、全心投入的團隊、我們的研究合作者和臨床研究人員團隊、我們的投資者和許多其他給予支持的個人，特別是我們的患者及其家人。

We are working tirelessly to deliver on the therapeutic potential of our pipeline and to transform the treatment landscape to the many individuals living with brain health disorders.

我們正在不懈地努力發揮我們的產品線的治療潛力，並改變許多患有大腦健康疾病的人的治療前景。

With that, I'd like to thank you all again for joining today.

在此，我要再次感謝大家今天的加入。

And the team and I are happy to take any questions.

我和團隊很樂意回答任何問題。

(Operator Instructions) Charles Duncan with Cantor.

（操作員指示）查爾斯鄧肯和康托爾。

Your line is now open.

您的線路現已開通。

Hi.

你好。

This is Elaine Kim on for Charles.

這是查爾斯的伊萊恩金 (Elaine Kim)。

Thank you for taking our questions.

感謝您接受我們的提問。

This is a two-parter.

這是一個二人組。

For the first question, is the open label 100 microgram dose to help maintain response or remission rates versus having patients continue the 50-microgram dose in the 40-week follow-up?

對於第一個問題，開放標籤 100 微克劑量是否有助於維持反應或緩解率，而不是讓患者在 40 週的追蹤中繼續使用 50 微克劑量？

And for my second question, is for reduction of the treatment session duration to 8 hours from 12 hours, what information enabled this decision to be agreed by the FDA and what requirements for patient care following the 8-hour treatment session, what requirements will be implemented?

對於我的第二個問題，是將治療時間從 12 小時減少到 8 小時，哪些資訊使 FDA 能夠同意這一決定，以及 8 小時治療後對患者護理的要求是什麼，將有哪些要求實施的？

Thank you.

謝謝。

Yeah.

是的。

Thanks so much, Elaine.

非常感謝，伊萊恩。

To the first question, so when we're designing the Phase 3 program, continuing patients on -- I think two things are worth pointing out with the open label Part B portion of the study, I should say, the extension Part B of the study versus that would be really thoughtful about how we analyze and think about the extension phase of the study because until patient has actually receive open label treatment in that Part B of the study, they remained in a blinded status until someone has actually received open label drug, while it's an extension study with open label opportunities for treatment they haven't actually received anything which is unusual here.

對於第一個問題，因此，當我們設計第3 階段計劃時，繼續讓患者繼續進行研究——我認為，在該研究的開放標籤B 部分部分中，有兩件事值得指出，我應該說，研究的B 部分的擴展與此相比，我們要認真考慮如何分析和思考研究的擴展階段，因為在患者真正接受研究B 部分中的開放標籤治療之前，他們一直處於盲態，直到有人真正接受了開放標籤治療。

It certainly wouldn't be the case -- in the case of open label extension of a daily medicine.

就日常藥物的開放標籤延伸而言，情況肯定不會是這樣。

The selection of 100 micrograms is because it is the clinical dose of interest.

選擇100微克是因為它是臨床感興趣的劑量。

Relying on our Phase 2b results, we believe, 100 microgram dose is our go-forward dose and our modeling from the Phase 2b results in the MCP-Mod analysis we conducted there suggests that it is the dose to take forward and the efficacious dose we should be studying.

根據我們的 2b 期結果，我們相信，100 微克劑量是我們的前進劑量，我們在 MCP-Mod 分析中根據 2b 期結果進行的建模表明，這是我們要推進的劑量，也是我們的有效劑量。應該在學習。

Whereas the 50-microgram dose, is there simply as a functional mask is an additional control to aid in addressing the concept of functional unblinding, that's the rationale.

而 50 微克劑量只是作為功能性面罩作為額外的控制來幫助解決功能性揭盲的概念，這就是基本原理。

We're not interested in 50-micogram as a clinical dose to take forward or to be submitted at this time.

我們對 50 微克作為目前推進或提交的臨床劑量不感興趣。

The intent is to characterize what happens in a more real world like setting or patients who have the opportunity for retreatment upon the reemergence or the continued in efficacy after the initial phase of the study.

目的是描述在更現實的世界中發生的情況，例如在研究初始階段後重新出現或持續有效時有機會接受再治療的環境或患者。

In terms of Part B of your question or the second part of your question, we presented data.

關於你問題的B部分或問題的第二部分，我們提供了數據。

So from very early on, I know this has been a point of discussion since the advisory committee earlier this year.

因此，從很早開始，我就知道自今年早些時候諮詢委員會以來，這一直是討論的焦點。

We have been very intentional about designing structured criteria for when patients would be allowed to end their monitoring session.

我們非常有意地設計了結構化標準，規定患者何時可以結束監測療程。

In Phase 2, we went to the extreme conservatism and used the DSM-5 definition of hallucinogen intoxication.

在第二階段，我們採取了極端保守的態度，並使用了 DSM-5 對致幻劑中毒的定義。

So patients had to be cleared by meeting effectively no signs of hallucinogen intoxication

因此，患者必須在沒有出現致幻劑中毒跡象的情況下才能被清除。

As we've continued our regulatory discussions and our thinking is further evolved and been informed by the data, we have refined that checklist to be much more modeled around what we would expect to be representative of a real-world RINs like checklist for releasing patients after a dosing session.

隨著我們繼續進行監管討論，我們的想法進一步發展並被數據所告知，我們已經完善了該清單，使其更加模仿我們期望代表現實世界 RIN 的內容，例如釋放患者的清單一次給藥後。

So we presented data, we collected a time course of those assessments in our Phase 2b study to characterize exactly the sort of temporal curve of when patients would be able to be part of a clinical dosing session and use those data to present to FDA and make the argument that shorter duration and monitoring is appropriate.

因此，我們提供了數據，我們在 2b 期研究中收集了這些評估的時間過程，以準確描述患者何時能夠參與臨床給藥療程的時間曲線，並使用這些數據向 FDA 提交並做出決定認為較短的持續時間和監測是適當的。

And as we go forward into Phase 3, Dan mentioned that the minimum required duration of monitoring in the Phase 3 will be 8 hours.

當我們進入第三階段時，Dan 提到第三階段所需的最短監控時間為 8 小時。

But we'll also be assessing the readiness for departure from a dosing session as early as 5 hour.

但我們也將最早在 5 小時內評估結束給藥療程的準備。

So that we'll be able to characterize again that response starting earlier than even the required monitoring here.

這樣我們就能夠再次描述該回應的特徵，甚至比這裡所需的監控更早開始。

But the ultimate goal, we believe that in a real world setting and when we think about labeling and RINs, there should be a required monitoring period if there is one that's at the far-left tail of the spectrum.

但最終目標是，我們相信，在現實世界中，當我們考慮標籤和 RIN 時，如果有一個位於頻譜的最左尾部，則應該有一個必需的監測期。

Physician discretion should be able to be employed, so minimizing the fixed duration of required monitoring is something that is of interest to us that we're continuing to build a structured base around to ensure that we have data in hand to make data informed arguments to the agency.

應該能夠運用醫生的自由裁量權，因此，我們感興趣的是盡量減少所需監測的固定持續時間，我們正在繼續圍繞這一點建立一個結構化基礎，以確保我們手頭有數據，可以為數據提供明智的論點。

That's very helpful.

這非常有幫助。

Thank you so much for taking all of our questions.

非常感謝您回答我們所有的問題。

Brian Abrahams, RBC Capital Markets.

布萊恩‧亞伯拉罕斯 (Brian Abrahams)，加拿大皇家銀行資本市場部。

Okay.

好的。

Got it.

知道了。

And then, how much dose dependence will you need to demonstrate between 50 and 100 micrograms in order to address the potential regulatory questions about functional unblinding.

然後，您需要證明 50 至 100 微克之間的劑量依賴性有多大，才能解決有關功能揭盲的潛在監管問題。

Do you need to show a statistical separation between those two arms or just a trend?

您需要顯示這兩個臂之間的統計分離還是僅顯示趨勢？

Thanks, I'll hop back in the queue.

謝謝，我會重新加入隊列。

Yeah.

是的。

This is a great and a really interesting question and one that we have both thought about extensively and internally as we designed our Phase 3 program and discussed extensively with the agency.

這是一個偉大且非常有趣的問題，在設計第三階段計劃並與該機構進行廣泛討論時，我們在內部進行了廣泛的思考。

Our view is that the 50-microgram control is simply there as a control.

我們的觀點是，50 微克對照只是作為對照。

It is not a statistical interest to us.

這對我們來說不是統計上的興趣。

Our Phase 2 study was intentionally designed to establish dose response.

我們的第 2 期研究是有意設計的，旨在建立劑量反應。

That was the primary analysis of the Phase 2 study, which we did with a high degree of statistical significance.

這是第二階段研究的主要分析，我們所做的具有高度的統計顯著性。

And as part of the MCP-Mod analysis, we come away with characterization of what we believe is the minimum clinically effective dose to achieve kind of clinical outcomes we're pursuing.

作為 MCP-Mod 分析的一部分，我們得出了我們認為實現我們所追求的臨床結果的最低臨床有效劑量的特徵。

That, coupled with the reality that in our Phase 2 study, we saw a high degree of functional unblinding or unmasking across all active doses of drug, but that only the two high doses achieved a clinical response.

再加上我們的第二期研究中的事實，我們看到所有活性劑量的藥物都具有高度的功能性揭盲或揭露，但只有兩種高劑量達到了臨床反應。

Our belief is that 100 microgram is the go-forward dose and that any other dose groups we include are not there to reestablish the dose response.

我們認為 100 微克是前進劑量，我們所包含的任何其他劑量組都不能重新建立劑量反應。

They're to try to confound patient expectancy.

他們試圖混淆患者的期望。

There's been a good degree of confusion, I think in the field about what the methodological things like an intermediate control group are there to do.

我認為，在這個領域，關於中間對照組等方法論的東西是做什麼的，存在著很大程度的混亂。

And there's been a lot of confusion about the differences and similarities between expectancy bias functional and blinding in these studies.

在這些研究中，函數期望偏差和盲法之間的差異和相似之處存在著許多困惑。

Our view is that 50 micrograms is a dose that overlaps with 100 microgram dose of clinical interest in terms of its perceptual effect, such that patients coming into the study would -- if the story we're ultimately trying to develop here is that when a patient comes into the study, with obviously a degree of expectancy because patients only enroll in clinical trials if they expect something to happen.

我們的觀點是，50 微克的劑量與臨床關注的 100 微克劑量在感知效果方面重疊，因此參與研究的患者會——如果我們最終在這裡試圖發展的故事是，當患者加入研究顯然帶有一定程度的期望，因為患者只有在期望發生某些事情時才會參加臨床試驗。

We'll be able to inform patients that if they feel the effects of a drug during a treatment session, they may be receiving a dose that is the active dose of drug or they may be receiving a dose that they will feel with a similar effect but that has been shown in previous studies to not be clinically active.

我們將能夠告知患者，如果他們在治療期間感受到藥物的作用，他們可能正在接受藥物活性劑量的劑量，或者他們可能正在接受他們會感受到類似效果的劑量但之前的研究表明這在臨床上並不活躍。

And so we're trying to mitigate the expectancy by it.

因此，我們正試圖透過它來降低預期。

The reality is that after a patient receives a dose, whether it be placebo, 50 micrograms or 100 micrograms, they will have the new knowledge of the feelings of the effect of that drug.

現實情況是，患者接受一劑藥物後，無論是安慰劑、50微克或100微克，都會對該藥物的效果有新的認識。

And we fundamentally believe that the feeling of the drug is the mechanism of the drug as is very often the case in psychiatry.

我們從根本上相信藥物的感覺就是藥物的機制，就像精神病學中經常出現的情況一樣。

And we do not intend or believe it is necessary to analyze statistically the 50-microgram dose.

我們不打算也不認為有必要對 50 微克劑量進行統計分析。

Our intent is to compare 100 micrograms versus placebo, which has been the regulatory standard for virtually all approved drugs, but certainly all approved drugs for GAD and for MDD.

我們的目的是比較 100 微克與安慰劑，幾乎是所有核准藥物的監管標準，當然也是所有核准的 GAD 和 MDD 藥物的監管標準。

And again, that 50 micrograms controlled in is simply there as an additional aid in functional blinding and to prove out the robustness of the 100-microgram dose effect across three different study designs and three different allocations.

再說一遍，控制的 50 微克只是作為功能性盲法的額外幫助，並證明 100 微克劑量效應在三種不同的研究設計和三種不同的分配中的穩健性。

That's really helpful.

這真的很有幫助。

Thanks so much.

非常感謝。

Rudy Li, Leerink Partners.

Rudy Li，Leerink 合夥人。

Hi.

你好。

Thanks for taking my question.

感謝您提出我的問題。

Congrats on the progress.

祝賀取得的進展。

Regarding the regulatory pathway in GAD, did you confirm with the FDA that the Phase 2b can be used as one of the pivotal trials or do you still means both Phase 3 trials to file NDA?

關於GAD的監管路徑，您是否已向FDA確認2b期試驗可以作為關鍵試驗之一，還是仍意味著兩項3期試驗都需要提交NDA？

And quickly, just a follow-up to Brian's question.

很快，我就回答布萊恩的問題。

With the first Phase 3 GAD starting in the second half of the year, what will be the rate limiting step for filing considering the 40-week of label retention trial?

隨著第一個 3 期 GAD 將於今年下半年開始，考慮到 40 週的標籤保留試驗，申請的速度限制步驟將是什麼？

Thanks.

謝謝。

Yeah.

是的。

Thanks so much, Rudy.

非常感謝，魯迪。

In terms of regulatory pathway, the Phase 2b study that we conducted is not a pivotal study.

就監管途徑而言，我們進行的 2b 期研究並不是關鍵研究。

We intend to file with two Phase 3 studies which are planned, the Voyage and Panorama studies.

我們打算提交兩項計劃中的第 3 階段研究，即 Voyage 和 Panorama 研究。

Secondly, in terms of the rate limiting, of course, we have come away with end of Phase 2 with a high degree of alignment.

其次，就速率限製而言，當然，我們在第二階段結束時保持了高度的一致性。

Always there's the caveat that many of the final decisions about what is going to be required for NDA are reserved for discussions at a pre-NDA meeting.

始終需要注意的是，許多有關 NDA 所需內容的最終決定都保留在 NDA 前會議上進行討論。

But our belief at this stage is that the completion of the Part A of Voyage and Panorama studies is the rate limiting factor to demonstrate two well-controlled studies that demonstrate the safety and efficacy of the drug.

但我們現階段的信念是，Voyage 和 Panorama 研究 A 部分的完成是證明兩項控制良好的研究的速率限制因素，這兩項研究證明了該藥物的安全性和有效性。

And that while we have an ongoing clinical pharmacology program, we will have Part B of the study that will be informative in that process, we believe a data cut from Part B of our Phase 3 studies would be adequate to enable submission.

雖然我們有一個正在進行的臨床藥理學項目，但我們將擁有該研究的B 部分，該部分將在該過程中提供信息，我們相信從我們的3 期研究B 部分中刪除的數據足以使提交成為可能。

Got it.

知道了。

Very helpful.

非常有幫助。

Thanks.

謝謝。

Francois Brisebois, Oppenheimer.

弗朗索瓦·布里斯布瓦，奧本海默。

Hi.

你好。

This is Dan on for Frank.

這是丹為弗蘭克代言。

Thanks for taking our questions.

感謝您回答我們的問題。

I guess related to some of the questions that have been going on.

我想這與一些一直存在的問題有關。

Could you talk a little bit more about the end-of-phase 2 meeting, especially considering the Lykos AdCom, whether there were any issues or concerns that were raised during the meeting?

您能否多談談第二階段結束會議，特別是考慮到 Lykos AdCom，會議期間是否提出了任何問題或擔憂？

And thanks for all the color around the strategies that you've taken but was there any surprises during the meeting.

感謝您所採取的策略的所有色彩，但會議期間是否有任何驚喜。

Anything you want to add there?

您想在那裡添加什麼嗎？

Yes.

是的。

Thanks so much for the question, Dan.

非常感謝你的提問，丹。

In Phase 2, we got fortunate in the sequencing of the regulatory events that have happened this year.

在第二階段，我們很幸運地對今年發生的監管事件進行了排序。

So we had our end of Phase 2 meeting very shortly after the Lykos Advisory Committee, which we thought it was a great benefit because it allowed us to integrate the thinking and feedback and obviously the public conversation from the Lykos AdCom into our discussions with the agency and something that we greatly value to us to be able to learn from other happenings in the field to make sure we're pursuing a strategy we're really confident.

因此，我們在Lykos 諮詢委員會召開後不久就召開了第二階段會議，我們認為這是一個很大的好處，因為它使我們能夠將想法和反饋以及來自Lykos AdCom 的公開對話整合到我們與該機構的討論中我們非常重視這一點，因為我們能夠從該領域的其他事件中學習，以確保我們正在推行我們真正有信心的策略。

And so we had a great discussion with the agency.

因此我們與該機構進行了深入的討論。

I think we came away with a high degree of alignment there are no surprises.

我認為我們達成了高度一致，這並不令人意外。

There's certainly a shared dialogue around trying to solve complex issues.

當然，圍繞著解決複雜問題進行了共同對話。

And I think we're incredibly appreciative of the agency in terms of their willingness to engage in those conversations, their willingness to be pragmatic and to tackle these complex issues in a way that doesn't slow down development.

我認為我們非常感謝該機構願意參與這些對話，願意務實並以不減慢發展速度的方式解決這些複雜問題。

Our view coming out of that meeting is that with the plan we have designed, we'll have a strong case to be made both to at the agency and to any commentators or observers or whether that be an advisory committee or and peer-reviewed publications and the broader narrative that we can go over the compelling argument for both the value proposition and the safety and efficacy of the drug that would allow us to then proceed to a submission.

我們從那次會議中得出的觀點是，根據我們設計的計劃，我們將向該機構以及任何評論員或觀察員，無論是諮詢委員會還是同行評審出版物提供強有力的理由以及更廣泛的敘述，我們可以回顧關於藥物的價值主張以及安全性和有效性的令人信服的論據，這將使我們能夠繼續提交。

So no surprises.

所以沒有什麼驚喜。

I would say that we had a very constructive dialogue and came up with a clear path forward.

我想說，我們進行了非常有建設性的對話，並提出了明確的前進道路。

Great.

偉大的。

And just as a quick follow-up, the dose relationship being -- going after 50 microgram and 100 micrograms.

作為快速跟進，劑量關係是——追求 50 微克和 100 微克。

Does the FDA generally agree with that approach that's demonstrating a dose relationship just address the expectancy bias or functional blinding issue?

FDA 是否普遍同意證明劑量關係只是解決預期偏差或功能性致盲問題的方法？

I think I understood your question.

我想我明白你的問題。

So we presented our view, and our logic, and our strategy, at end of our Phase 2 meeting and in our Phase 3 protocols, and we're certainly confident in the path forward and our plans to address these issues.

因此，我們在第二階段會議結束時和第三階段協議中提出了我們的觀點、我們的邏輯和我們的策略，我們對解決這些問題的前進道路和計劃充滿信心。

I think it's really important to -- for us to highlight the reality that this is a very common issue in psychiatry, while there's been a sort of spotlight shown on the matter of expectancy and functional unblinding.

我認為對我們來說，強調這是精神病學中一個非常常見的問題這一現實非常重要，同時人們對預期和功能性揭盲問題也給予了一定的關注。

This is how psychiatry drugs work, particularly for mood and anxiety disorders.

這就是精神科藥物的作用原理，特別是對於情緒障礙和焦慮症。

2 milligrams of Xanax is fully functionally unblinded and based on historical research, even SRIs have something like a 70% incidence of patients being able to correctly guess they're on SRI.

2 毫克 Xanax 是完全功能性非盲的，並且基於歷史研究，即使是 SRI，患者也有大約 70% 的幾率能夠正確猜測他們正在服用 SRI。

It's only that under 5% of historical studies of SRIs that actually asked the question or appeared to look.

只有不到 5% 的 SRI 歷史研究真正提出了這個問題或看起來如此。

So while this is being scrutinized in our field, it's not unusual and in that, we believe that we should follow the well-established precedents for evidence required to establish the safety and efficacy of drugs, which is demonstrating statistically and clinically significant improvement over placebo.

因此，雖然這在我們的領域正在受到審查，但這並不罕見，因此，我們認為我們應該遵循既定的先例來獲取確定藥物安全性和有效性所需的證據，這表明在統計和臨床上比安慰劑有顯著改善。

That's what our program is designed around.

這就是我們的程式的設計初衷。

And while we include many, many aspects to try to mitigate and address the questions around expectancy and functional unblinding, we have a line that we believe with the agency on the path forward.

雖然我們包括了很多很多方面來試圖減輕和解決有關預期和功能揭盲的問題，但我們相信該機構在前進的道路上有一條路線。

Again, this is just something that is not all of that new even though it's been highly talked about over the last couple of months.

再說一遍，這並不是什麼新鮮事，儘管在過去幾個月裡它受到了廣泛的關注。

Great.

偉大的。

Thanks for taking our questions.

感謝您回答我們的問題。

(Operator Instructions) Joel Beatty, RW Baird.

（操作員說明）Joel Beatty，RW Baird。

Good morning, This is Christopher Chen on for Joel.

早安，我是喬爾的克里斯多福陳。

Thanks for taking our question.

感謝您提出我們的問題。

In terms of 120, I know your primary focus is the domestic market, but have you started at all analyzing ex-US opportunities?

就120而言，我知道您的主要關注點是國內市場，但是您是否開始分析美國以外的機會？

And if so, how would you characterize that analysis?

如果是這樣，您如何描述該分析？

Thank you.

謝謝。

Yeah.

是的。

Thanks so much, Christopher.

非常感謝，克里斯多福。

We have started to analyze ex-US markets and engage in certainly some dialogue about those opportunities.

我們已經開始分析美國以外的市場，並就這些機會進行一些對話。

We do not, at this time, intend to develop a sales force or launch the drug.

目前，我們不打算培養銷售隊伍或推出該藥物。

In most ex-US markets, our focus would be on the US markets.

在大多數美國以外市場，我們的重點是美國市場。

And we're certainly open to engaging and discussing collaborations and partnerships ex-US when it makes sense about commercialization on those markets.

當這些市場的商業化有意義時，我們當然願意參與和討論美國以外的合作和夥伴關係。

But obviously, the dynamics of, for instance, launching a drug in Europe and the pricing and various considerations there would be we think a lower return on investment than our focus on launching the drug in the US primarily.

但顯然，例如在歐洲推出一種藥物的動態以及定價和各種考慮因素，我們認為投資回報率會低於我們主要在美國推出該藥物的投資回報率。

Thank you.

謝謝。

Sumant Kulkarni, Canaccord Genuity LLC.

Sumant Kulkarni，Canaccord Genuity LLC。

Good morning.

早安.

Thanks for taking my questions.

感謝您回答我的問題。

Do you have any specific targets for prior use of LSD or other psychedelic inclusion criteria in your Phase 3 trials?

對於先前使用 LSD 或在 3 期試驗中使用其他迷幻藥的納入標準，您有任何具體目標嗎？

And in the open-label portions of your studies, how do you ensure integrity is maintained to make sure that any potential durability of effect is more purely attributable to MM120 versus other treatments or therapy?

在您研究的開放標籤部分中，您如何確保保持完整性，以確保任何潛在的持久效果更純粹地歸因於 MM120 而不是其他治療或療法？

Yeah.

是的。

Thanks so much, Sumant.

非常感謝，蘇曼特。

I'll turn that over to Dan Karlin to address that one.

我會將其轉交給 Dan Karlin 來解決這個問題。

Yeah.

是的。

So thanks, Sumant.

謝謝，蘇曼特。

For prior psychedelic or LSD exposure, we have explicit exclusion criteria related to recent use and any heavy use over a number of years, preceding enrollment.

對於先前接觸過致幻劑或 LSD 的情況，我們有明確的排除標準，涉及近期使用以及入組前多年的任何大量使用。

So while we don't specify beyond that from an inclusion and exclusion perspective, we certainly want to be sure that we're getting folks who aren't currently using or recent heavy users.

因此，雖然我們沒有從包含和排除的角度對此進行詳細說明，但我們當然希望確保我們吸引的是目前未使用或最近大量使用的用戶。

We also will in Phase 2b track, use history, of course.

當然，我們還將在第 2b 階段跟踪，使用歷史記錄。

And what we found in Phase 2 was, in essence, with these criteria because we're moving into Phase 3 very much with the inclusion exclusion mirroring Phase 2.

我們在第二階段發現的內容本質上是符合這些標準的，因為我們正在進入第三階段，包含排除與第二階段相似。

What we found was about a 15% to 20% historical usage in the population we ended up enrolling, which interestingly aligns almost exactly with epidemiological findings used in the general population.

我們發現，在我們最終招募的人群中，大約有 15% 到 20% 的歷史使用情況，有趣的是，這與一般人群中使用的流行病學調查結果幾乎完全一致。

So as ever, we want to get a population that is representative of the overall GAD population as possible.

因此，與以往一樣，我們希望獲得盡可能代表 GAD 整體人群的人群。

I think we did that in Phase 2, and we'll continue to do that in Phase 3.

我認為我們在第二階段就做到了這一點，我們將在第三階段繼續這樣做。

As far as data integrity, attribution of efficacy, the extension phase that we discussed, and that Rob expanded on a bit in a prior question is really going to be run very much the same way that the blinded phase is run.

就資料完整性、功效歸因、我們討論的擴展階段以及 Rob 在先前問題中進行的擴展而言，實際上將以與盲階段運行方式非常相同的方式運行。

So that in all of our studies, we watch people out of background therapy if folks are engaging in psychotherapy outside of the trial, that has to be stable and unchanging for a period of time both before and through the trial.

因此，在我們所有的研究中，如果人們在試驗之外進行心理治療，我們會觀察人們脫離背景治療，這必須在試驗前和試驗期間的一段時間內保持穩定和不變。

And we'll continue to enforce those same restrictions on outside treatment, other treatments, newly added psychotherapy through the entire extension phase.

在整個延長階段，我們將繼續對外部治療、其他治療、新增加的心理治療實施同樣的限制。

So while we do give folks the opportunity to get either dosed for the first time if they started in a placebo arm or a control arm, the expectation is that the only treatment that they're receiving the only new or change treatment that they're receiving and the only pharmacological treatment that they're receiving through the entire extension phase is MM120.

因此，雖然我們確實為人們提供了第一次服用安慰劑或對照組的機會，但我們期望他們接受的唯一治療是他們正在接受的唯一新的或改變的治療他們在整個延長階段接受的唯一藥物治療是MM120。

Thank you.

謝謝。

Thank you.

謝謝。

And I'm currently showing no further questions in the queue.

目前我在隊列中沒有顯示任何其他問題。

This does conclude today's conference call.

今天的電話會議到此結束。

Thank you all for joining and you may now disconnect.

感謝大家的加入，現在可以斷開連線了。