Compass Pathways PLC (CMPS) 2022 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the COMPASS Pathways conference call. (Operator Instructions) As a reminder, this call is being recorded. I would now like to introduce your host for today's conference, Stephen Schultz. You may begin.

女士們先生們，美好的一天，歡迎來到 COMPASS Pathways 電話會議。 （操作員說明）提醒一下，此通話正在錄音中。現在，我想介紹一下今天會議的主持人斯蒂芬·舒爾茨 (Stephen Schultz)。你可以開始了。

Welcome all of you, and thank you for joining us today for our fourth quarter and year-end 2022 results conference call. Again, my name is Steve Schultz. I'm the Senior Vice President of Investor Relations at COMPASS Pathways. And today, I'm joined by Kabir Nath, our Chief Executive Officer; and Mike Falvey, our Chief Financial Officer. Dr. Guy Goodwin, our Chief Medical Officer, is unable to join us today. So Kabir will be covering clinical development.

歡迎大家，並感謝您今天加入我們的第四季度和 2022 年底業績電話會議。再一次，我的名字是史蒂夫舒爾茨。我是 COMPASS Pathways 的投資者關係高級副總裁。今天，我們的首席執行官 Kabir Nath 也加入了我的行列；以及我們的首席財務官 Mike Falvey。我們的首席醫療官 Guy Goodwin 博士今天無法加入我們。因此，Kabir 將負責臨床開發。

The call is being recorded and will be available on the COMPASS Pathways Investor Relations website shortly after the conclusion of the call.

通話正在錄音中，通話結束後不久將在 COMPASS Pathways 投資者關係網站上公佈。

Before we begin, let me remind everyone that during the call today, the team will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as amended. You should not place undue reliance on these forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those risks and uncertainties described under the heading Risk Factors in our annual report on Form 10-K filed with the U.S. Securities and Exchange Commission and in subsequent filings made by COMPASS with the SEC.

在我們開始之前，讓我提醒大家，在今天的電話會議中，該團隊將根據 1995 年《私人證券訴訟改革法案》修正案的含義做出前瞻性陳述。您不應過分依賴這些前瞻性陳述。由於各種風險、不確定性和其他因素，包括我們 10-K 表年度報告中風險因素標題下描述的風險和不確定性，實際事件或結果可能與任何前瞻性陳述明示或暗示的事件或結果存在重大差異已向美國證券交易委員會備案，隨後由 COMPASS 向美國證券交易委員會提交備案文件。

Additionally, these forward-looking statements represent our views only as of today and should not be relied upon as representing our views at any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements, even if our estimates or assumptions change. I will now hand the call over to Kabir Nath.

此外，這些前瞻性陳述僅代表我們截至今日的觀點，不應被視為代表我們在任何後續日期的觀點。我們特別聲明不承擔任何更新或修改任何前瞻性陳述的義務，即使我們的估計或假設發生變化。我現在將把電話交給 Kabir Nath。

Thank you, Steve. Good day, everyone, and thank you for joining us. We have quite a bit to share with you as we continue to make strong progress across all aspects of our business. During this past quarter, we started our COMP360 Phase III pivotal program in treatment-resistant depression, or TRD, a unique achievement, the first ever Phase III trial of psilocybin.

謝謝你，史蒂夫。大家好，感謝您加入我們。隨著我們在業務的各個方面繼續取得長足進步，我們有很多話要與您分享。在過去的這個季度，我們啟動了 COMP360 治療抵抗性抑鬱症的 III 期關鍵計劃，或 TRD，這是一項獨特的成就，是裸蓋菇素的第一個 III 期試驗。

As you know, this is a field that holds the potential for significant advances in the treatment of mental health conditions, and we're thrilled to be at the forefront of this potential paradigm shift. Today, we're announcing an important update to the Phase III program we described last fall, starting with our COMP 005 trial. As a reminder, this is the single dose monotherapy trial comparing a 25-milligram dose of COM360 to a true placebo. We've completed further analysis of our Phase IIb data with specific focus on the participants in the 1-milligram arm who had a minimal psychedelic experience as well as analysis of a recent data from a placebo-controlled study at the University of Zurich using COMP360 in major depressive disorder or MDD.

如您所知，這是一個有可能在治療心理健康狀況方面取得重大進展的領域，我們很高興能站在這一潛在範式轉變的最前沿。今天，我們宣布對我們去年秋天描述的 III 期計劃進行重要更新，從我們的 COMP 005 試驗開始。提醒一下，這是將 25 毫克劑量的 COM360 與真正的安慰劑進行比較的單劑量單一療法試驗。我們已經完成了對 IIb 期數據的進一步分析，特別關注 1 毫克組中具有最少迷幻體驗的參與者，以及對蘇黎世大學使用 COMP360 進行的一項安慰劑對照研究的最新數據的分析在重度抑鬱症或 MDD 中。

This data-driven analysis has led to a re-estimation of the sample size for the COMP 005 trial and a revision to a lower expected response to true placebo. This allows us to reduce the number of patients required in the 005 trial to 255 from the original 378 while maintaining the power to achieve our objectives.

這種數據驅動的分析導致對 COMP 005 試驗的樣本量進行了重新估計，並修正了對真正安慰劑的較低預期反應。這使我們能夠將 005 試驗所需的患者人數從最初的 378 人減少到 255 人，同時保持實現我們目標的能力。

With the reduction in the number of patients, we now expect to complete the pivotal component of this trial, the 6-week primary endpoint, by summer 2024 rather than the end of 2024 as we previously guided. Additionally, we finalized the plans for long-term follow-up for the Phase III program. Building off the lessons from COMP 004, the long-term follow-up trial Phase IIb study, our strategy is to integrate the follow-up into the 2 pivotal trials, which we believe will enable a more streamlined design, reduce selection bias and the implementation burden on our patients and clinicians.

隨著患者數量的減少，我們現在預計到 2024 年夏季而不是我們之前指導的 2024 年底完成該試驗的關鍵部分，即 6 週的主要終點。此外，我們還完成了 III 期項目的長期隨訪計劃。基於 COMP 004 的經驗教訓，長期隨訪試驗 IIb 期研究，我們的策略是將隨訪納入 2 項關鍵試驗，我們相信這將實現更精簡的設計，減少選擇偏差和我們的患者和臨床醫生的實施負擔。

Again, to remind you, the 2 pivotal trials are COMP 005, which I described just now, and COMP 006, a fixed repeat dose monotherapy trial with 3 arms, comparing COMP360 doses of 25 milligrams, 10 milligrams and 1 milligram where patients will receive the same dose at day 1 and week 3. In both trials, we will follow patients up to 52 weeks, building on the 6-week pivotal analysis of each trial, which we're calling Part A.

再次提醒您，這兩項關鍵試驗是我剛才描述的 COMP 005 和 COMP 006，這是一項固定重複劑量單藥治療試驗，有 3 個臂，比較了患者將接受的 25 毫克、10 毫克和 1 毫克的 COMP360 劑量在第 1 天和第 3 週服用相同的劑量。在這兩項試驗中，我們將對患者進行長達 52 週的隨訪，以每項試驗的 6 週關鍵分析為基礎，我們將其稱為 A 部分。

The design follows the same principles for each trial. Part B of each trial will follow from the primary endpoint assessment at 6 weeks to 26 weeks. Patients who meet criteria for retreatment in Part B will have the option to receive a further treatment according to their original allocation in both studies, thus preserving the randomized comparison between arms to 26 weeks. Part C will run from 26 weeks to 52 weeks as an open-label component of the trial. Importantly, all patients who meet criteria for retreatment in Part C will have the option to receive a single 25-milligram dose of COM360 open label. This option is expected to support patient engagement throughout the entire duration of the trials.

每次試驗的設計都遵循相同的原則。每個試驗的 B 部分將遵循 6 周至 26 週的主要終點評估。符合 B 部分再治療標準的患者將可以選擇根據他們在兩項研究中的原始分配接受進一步治療，從而將兩組之間的隨機比較保留到 26 週。 C 部分作為試驗的開放標籤部分將持續 26 周至 52 週。重要的是，所有符合 C 部分再治療標準的患者都可以選擇接受單次 25 毫克劑量的 COM360 開放標籤。該選項有望在整個試驗期間支持患者參與。

It's important to emphasize that there is no change to the primary endpoint of either trial, which is change in MADRS from baseline at 6 weeks nor to our intention to announce the top line results from the primary endpoint of each trial at that time. We're confident that this trial design will provide insights to key questions on durability of effect and the value of retreatment. Moreover, TRD often behaves like a chronic condition. By following patients with continuing randomization for 26 weeks, much longer than is conventional in other major depressive disorder trials, we have the potential to generate unique durability and retreatment data, which could enhance the value of COM360. We believe that these amendments will help to generate further evidence that enhances our Phase III program and the potential benefit to patients, clinicians, regulators and payers.

重要的是要強調，這兩項試驗的主要終點沒有變化，即 MADRS 從 6 週時的基線開始發生變化，也沒有我們打算在那時宣布每個試驗的主要終點的頂線結果。我們相信，該試驗設計將為有關效果持久性和再治療價值的關鍵問題提供見解。此外，TRD 通常表現為慢性病。通過持續隨機化跟踪患者 26 週（比其他主要抑鬱症試驗中的常規時間長得多），我們有可能生成獨特的耐久性和再治療數據，這可以提高 COM360 的價值。我們相信，這些修正案將有助於產生進一步的證據，以加強我們的 III 期計劃，並為患者、臨床醫生、監管機構和付款人帶來潛在利益。

We've submitted these protocol amendments to the FDA who have indicated they will come back to us by March 20 on 005 if they had any further comments following their earlier feedback on durability and retreatment design principles. I remind you that this Phase III program is already underway and that it's routine to have an ongoing dialogue with the FDA as we conduct the trials, especially with our breakthrough therapy designation. If we do receive further comments, we will, of course, consider that feedback.

我們已將這些協議修正案提交給 FDA，FDA 表示如果他們在先前對耐久性和再處理設計原則的反饋後有任何進一步的評論，他們將在 3 月 20 日 005 之前回复我們。我提醒您，這個 III 期計劃已經在進行中，並且在我們進行試驗時與 FDA 進行持續對話是例行公事，特別是在我們的突破性治療指定方面。如果我們確實收到進一步的評論，我們當然會考慮該反饋。

Let me now turn to the broader body of evidence we're developing for COM360. The Phase II PTSD program is progressing with COMP360 dosing of enrolled patients. In December, data from an exploratory open-label, investigator-led initiative in bipolar depression type 2 were presented by the investigator at the Annual Meeting of the American College of Neuropsychopharmacology. This study investigated the safety and efficacy of a single 25-milligram dose of COMP360 psilocybin therapy in 14 patients.

現在讓我轉向我們正在為 COM360 開發的更廣泛的證據。 II 期 PTSD 計劃正在對登記的患者進行 COMP360 給藥。 12 月，研究者在美國神經精神藥理學學會年會上介紹了一項探索性開放標籤、研究者主導的 2 型雙相抑鬱症倡議的數據。本研究調查了 14 名患者使用單次 25 毫克劑量的 COMP360 裸蓋菇素治療的安全性和有效性。

The results showed positive early signals of efficacy with 12 of the 14 patients meeting response and remission criteria for the MADRS scale at 12 weeks after COM360 psilocybin therapy. Notably, no subject had manic or hypomanic symptoms or an increase in suicidal ideation. We believe that these are remarkable data and provide further evidence to support the potential of COMP360 psilocybin therapy for difficult-to-treat depression. I remind you, though, that this was a small study, and these findings now need to be validated in larger studies.

結果顯示，在 COM360 裸蓋菇素治療後 12 週，14 名患者中有 12 名符合 MADRS 量表的反應和緩解標準，顯示出積極的早期療效信號。值得注意的是，沒有受試者出現躁狂或輕躁狂症狀或自殺意念增加。我們相信，這些都是了不起的數據，並提供了進一步的證據來支持 COMP360 psilocybin 治療難治性抑鬱症的潛力。不過，我提醒你，這是一項小型研究，這些發現現在需要在更大規模的研究中進行驗證。

Also, in December, the Zurich study in MDD, which I referenced earlier, was published. This randomized blinded study enrolled 52 patients comparing a weight-based variable dose of COM360 to true placebo and demonstrated compelling efficacy results with no new safety signal. We see this as further evidence of the potential for COM360 to help patients living with serious mental illness.

此外，在 12 月，我之前提到的 MDD 蘇黎世研究發表了。這項隨機盲法研究招募了 52 名患者，將基於體重的可變劑量 COM360 與真正的安慰劑進行比較，並在沒有新的安全信號的情況下展示了令人信服的療效結果。我們認為這是 COM360 幫助患有嚴重精神疾病的患者的潛力的進一步證據。

Turning to anorexia nervosa. This remains an area of critical unmet need with no FDA-approved pharmaceutical product and the highest mortality rate of any serious mental illness. We're committed to pioneering a robust Phase II trial to build on the evidence already generated in investigator-initiated studies. I remind you that there is no significant body of experience available for this indication, so we are on a steep learning curve.

轉向神經性厭食症。這仍然是一個關鍵的未滿足需求的領域，沒有 FDA 批准的藥物產品，也是任何嚴重精神疾病死亡率最高的領域。我們致力於開創一項強有力的 II 期試驗，以建立在研究者發起的研究中已經產生的證據的基礎上。我提醒您，目前還沒有針對該適應症的大量經驗，因此我們正處於陡峭的學習曲線上。

We've learned that we need to make amendments to our protocol to better meet the needs of this highly vulnerable patient population. As a result, it's unlikely that we will see top line data in 2023. Please note that this is a very different patient population from TRD patients, treated largely by different physicians at specialized centers and that the need to amend this protocol has no impact on our Phase III TRD program.

我們了解到，我們需要對我們的協議進行修改，以更好地滿足這一高度脆弱的患者群體的需求。因此，我們不太可能在 2023 年看到頂線數據。請注意，這是一個與 TRD 患者截然不同的患者群體，主要由專門中心的不同醫生治療，修改該協議的需要對我們的第三階段 TRD 計劃。

In closing, let me reiterate that we believe the last quarter of 2022 was a quarter of strong progress, capping a year of extraordinary progress for COMPASS Pathways. Our Phase III study, the largest, most robust ever study in psilocybin is underway, and we're excited to continue the journey to bring COMP360 psilocybin therapy with psychological support to patients, subject to study results and regulatory approval. I'll now hand the call to Mike for the financial overview.

最後，讓我重申，我們認為 2022 年最後一個季度是取得強勁進展的一個季度，為 COMPASS Pathways 取得非凡進展的一年畫上了句號。我們的 III 期研究正在進行中，這是有史以來規模最大、最穩健的裸蓋菇素研究，我們很高興能夠繼續為患者提供 COMP360 裸蓋菇素治療和心理支持的旅程，具體取決於研究結果和監管部門的批准。我現在將電話轉給 Mike 以了解財務概況。

Thank you, Kabir. I will start with a brief summary of the full year results and then review the fourth quarter results in more detail. For the year ended December 31, 2022, net loss was $91.5 million or $2.16 per share compared with a net loss of $71.7 million or $1.79 per share during the same period in 2021. These results include noncash share-based compensation of $13.1 million in 2022 and $8.6 million in 2021. R&D expenses were $65.1 million compared with $44 million during the same period in 2021. And G&A expenses were $45.4 million compared with $39.2 million during the same period in 2021. Our fourth quarter results reflect the commencement of our Phase III trial in TRD in a number of places. For the 3 months ended December 31, 2022, net loss was $30.9 million or $0.73 per share compared with a net loss of $18.4 million or $0.43 per share for the 3 months ended September 30, 2022. These results include noncash share-based compensation of $3.3 million in the fourth quarter and $3.5 million in the third quarter.

謝謝你，卡比爾。我將從簡要總結全年業績開始，然後更詳細地回顧第四季度業績。截至 2022 年 12 月 31 日止年度，淨虧損為 9150 萬美元或每股 2.16 美元，而 2021 年同期為淨虧損 7170 萬美元或每股 1.79 美元。這些結果包括 2022 年 1310 萬美元的非現金股權補償2021 年為 860 萬美元。研發費用為 6510 萬美元，而 2021 年同期為 4400 萬美元。G&A 費用為 4540 萬美元，而 2021 年同期為 3920 萬美元。我們第四季度的業績反映了我們第三階段的開始在許多地方進行 TRD 試驗。截至 2022 年 12 月 31 日的三個月，淨虧損為 3090 萬美元或每股 0.73 美元，而截至 2022 年 9 月 30 日的三個月淨虧損為 1840 萬美元或每股 0.43 美元。這些結果包括非現金股份補償第四季度為 330 萬美元，第三季度為 350 萬美元。

R&D expenses were $19.8 million in the fourth quarter compared with $14 million in the third quarter due to the Phase III start. The growth in R&D outside development spending and personnel expenses were due to our Phase III trial. G&A expenses were $12.4 million in the fourth quarter compared with $11.6 million in the third quarter. This increase was due to increased personnel and facility costs, partially offset by decreased legal and professional fees. We believe that COMPASS continues to maintain a strong financial position with cash and cash equivalents of $143.2 million at December 31, 2022, compared with $173.1 million at September 30, 2022, and $273.2 million at December 31, 2021.

由於 III 期的啟動，第四季度的研發費用為 1980 萬美元，而第三季度為 1400 萬美元。研發外部開發支出和人員支出的增長是由於我們的 III 期試驗。第四季度的 G&A 費用為 1240 萬美元，而第三季度為 1160 萬美元。這一增長是由於人員和設施成本的增加，部分被法律和專業費用的減少所抵消。我們認為，COMPASS 繼續保持強勁的財務狀況，截至 2022 年 12 月 31 日，現金和現金等價物為 1.432 億美元，而 2022 年 9 月 30 日為 1.731 億美元，2021 年 12 月 31 日為 2.732 億美元。

Our cash balance decreased by $29.9 million in the fourth quarter of 2022 due to using $45.3 million in operating cash, partially offset by a change of $14.9 million due to the impact of exchange rates on our cash balances held in British pounds. The movement in operating cash is largely driven by our net loss, partially reduced by noncash charges and also increases from a number of prepaid Phase III expenses to our CRO, which will be used to support R&D expenses over the next few quarters as our program progresses. This cash usage was partially offset by $8.5 million we received this quarter for our 2021 U.K. R&D tax credit.

由於使用了 4530 萬美元的運營現金，我們的現金餘額在 2022 年第四季度減少了 2990 萬美元，但由於匯率對我們以英鎊持有的現金餘額的影響而產生的 1490 萬美元的變化部分抵消了這一變化。經營現金的變動主要是由我們的淨虧損驅動的，部分因非現金費用而減少，並且還從一些預付的第三階段費用增加到我們的 CRO，隨著我們計劃的進展，這些費用將用於支持未來幾個季度的研發費用.這一現金使用量被我們本季度收到的 2021 年英國研發稅收抵免 850 萬美元部分抵消。

Our cash balance also reflects an increase to record the impact of currency exchange rates on our cash balance. After 2 consecutive quarters of declines, the British pound appreciated versus the dollar in the fourth quarter. As a reminder, we hold our cash balances in dollars, pounds and euros in proportion to our spending plans in each currency. Since we intend to spend these balances rather than exchange them, fluctuations in foreign exchange rates are not expected to significantly impact our cash runway, which continues to fund our operations for at least the next 12 months.

我們的現金餘額也反映了記錄貨幣匯率對我們現金餘額的影響的增加。在連續兩個季度下跌後，英鎊兌美元在第四季度出現升值。提醒一下，我們持有美元、英鎊和歐元的現金餘額與我們在每種貨幣上的支出計劃成比例。由於我們打算花掉這些餘額而不是兌換它們，因此預計匯率波動不會對我們的現金跑道產生重大影響，至少在未來 12 個月內，現金跑道將繼續為我們的運營提供資金。

We view our strong balance sheet as an important strategic asset, which we intend to manage carefully as we invest to advance promising potential therapies, while at the same time, continuing to create value for our shareholders. As previously indicated, we are providing financial guidance for the first quarter and the full year 2023.

我們將強大的資產負債表視為一項重要的戰略資產，我們打算在投資推進有前途的潛在療法時對其進行謹慎管理，同時繼續為股東創造價值。如前所述，我們將提供 2023 年第一季度和全年的財務指導。

We expect the first quarter net cash used in operating activities to be in the range of $24 million to $32 million and the full year to be in the range of $85 million to $110 million. The first quarter range is due to the challenge in predicting the precise timing of cash outlays to support the Phase III program in its start-up phase. As the trial reaches steady state enrollment in future quarters, we plan to offer a narrower quarterly range. Thank you, and I'll now turn the call back to Kabir.

我們預計第一季度用於經營活動的淨現金在 2400 萬美元至 3200 萬美元之間，全年將在 8500 萬美元至 1.1 億美元之間。第一季度的範圍是由於預測現金支出的準確時間以支持處於啟動階段的 III 期計劃的挑戰。隨著試驗在未來幾個季度達到穩態註冊，我們計劃提供更窄的季度範圍。謝謝，我現在將電話轉回卡比爾。

Thank you, Mike. With our lead asset COM360 in Phase III, we continue to be an industry leader in our area of science, addressing complex therapeutic challenges. Treatment-resistant depression is the first target indication, but we believe that COM360 psilocybin therapy has potential for broad application. We also continue to advance our commercial strategy. An important step towards this objective is to have reimbursement codes, called CPT codes, in place at launch.

謝謝你，邁克。憑藉我們處於 III 期的主要資產 COM360，我們將繼續成為我們科學領域的行業領導者，應對複雜的治療挑戰。難治性抑鬱症是第一個目標適應症，但我們相信 COM360 psilocybin 療法具有廣泛應用的潛力。我們還繼續推進我們的商業戰略。朝著這個目標邁出的重要一步是在發佈時使用補償代碼，稱為 CPT 代碼。

In February, we participated in the meeting focused on the final stages of this process, and we hope to have the new tracking CPT code available soon, and this would be the precursor to the final commercial code.

2 月，我們參加了專注於此過程最後階段的會議，我們希望盡快提供新的跟踪 CPT 代碼，這將是最終商業代碼的前身。

Our robust and comprehensive strategy is designed to support both the COM360 psilocybin therapy regulatory approval as well as provide the evidence needed by payers to reimburse this new therapy upon launch. We believe that this strategy can lead to significant value creation as we continue to execute successfully.

我們強大而全面的戰略旨在支持 COM360 psilocybin 療法的監管批准，並為付款人提供所需的證據，以在新療法上市後報銷。我們相信，隨著我們繼續成功執行，這一戰略可以帶來巨大的價值創造。

Thank you once again for your participation in today's call. And we'll now turn to Q&A, so I will hand the call back to the operator. Thank you.

再次感謝您參與今天的電話會議。現在我們將轉向問答環節，所以我會將電話轉回給接線員。謝謝。

(Operator Instructions) And our first question is from Charles Duncan with Cantor Fitzgerald.

（操作員說明）我們的第一個問題來自 Charles Duncan 和 Cantor Fitzgerald。

Thanks for the update on the Phase III program that was interesting. I did have a couple of questions to ask you on that. I guess I'm wondering if you could provide a little bit more color on what you saw out of the prior trial, the 1-milligram, of responses that you saw. And clearly, that has resulted in a sample size adjustment downward. But can you also give us some thoughts on whether or not that changes your perspective on effect size ultimately that you're looking for out of this study?

感謝您更新有趣的 III 期計劃。我確實有幾個問題要問你。我想我想知道您是否可以為您在之前的試驗中看到的 1 毫克反應提供更多顏色。顯然，這導致樣本量下調。但是，您能否也給我們一些想法，看看這是否最終會改變您對您從這項研究中尋找的效果大小的看法？

Thanks for the question, Chaz. So in the Phase IIb, as you'll recall, the 1-milligram was effectively the control. And as we were able to do further analysis, as you'd expect, given this was a largely naive population, naive to psychedelics, we saw a range of psychedelic experience in the patients on the 1-milligram arm, but the majority clustered around essentially no psychedelic experience.

謝謝你的問題，查茲。所以在 IIb 階段，你會記得，1 毫克是有效的控制。正如您所期望的那樣，我們能夠進行進一步的分析，鑑於這主要是天真的人群，對迷幻藥很天真，我們在 1 毫克組的患者中看到了一系列迷幻體驗，但大多數人聚集在周圍基本上沒有迷幻體驗。

And that, for us, kind of conforms to something that looks like a placebo response. When we actually were able to analyze that, we were able to see a strong correlation between that and lack of outcome. And that was our internal data from the Phase IIb data. We were then able to validate some of our thinking around that with the data from the Zurich study in MDD, which again used a pure placebo arm. And that, again, was able to validate our assumptions around, in fact, a likely lower difference from baseline in MADRS on the true placebo arm in COM 005.

而且，對我們來說，有點符合看起來像安慰劑反應的東西。當我們真正能夠對其進行分析時，我們能夠看到它與缺乏結果之間存在很強的相關性。那是我們來自 IIb 期數據的內部數據。然後，我們能夠使用來自 MDD 的蘇黎世研究的數據來驗證我們圍繞這一點的一些想法，該研究再次使用了純安慰劑組。而且，這再次能夠驗證我們的假設，事實上，在 COM 005 的真正安慰劑組上，MADRS 與基線的差異可能較低。

As you recall, COM 006, of course, uses the same 3 arms as the IIb, so we can assume something around the treatment difference there. We haven't disclosed and don't intend to disclose the actual treatment differences that we are powering for. But what I can confirm is that from our perspective, we are very comfortable that we are looking at a different treatment difference for the true placebo arm. We're maintaining the power with the reduced size, but we are confident that, that will not affect the integrity or the validity of the outcome.

正如您所記得的，COM 006 當然使用與 IIb 相同的 3 個臂，因此我們可以假設一些圍繞那裡的治療差異。我們尚未披露，也不打算披露我們力求實現的實際待遇差異。但我可以確認的是，從我們的角度來看，我們很高興看到真正的安慰劑組有不同的治療差異。我們通過減小尺寸來保持功率，但我們相信，這不會影響結果的完整性或有效性。

Makes sense, sounds like the delta is actually bigger. If I may just ask one brief follow-up and then I'll hop back in the queue. And that is, in terms of the patient engagement that you mentioned with Part B being able to take patients out through 26 weeks. I'm really intrigued with that. I guess I'm wondering if that was the result of some feedback from agency or more importantly, investigators suggesting that, that's what patients wanted. Or was that just some thinking on your part to suggest that you could really add some value for patients if you knew that the drug worked over time.

有道理，聽起來三角洲實際上更大。如果我可以只問一個簡短的後續問題，然後我會跳回到隊列中。也就是說，就您在 B 部分中提到的患者參與而言，能夠在 26 週內將患者帶出。我對此很感興趣。我想我想知道這是否是機構反饋的結果，或者更重要的是，調查人員暗示，這就是患者想要的。或者這只是您的一些想法，表明如果您知道該藥物會隨著時間的推移起作用，那麼您真的可以為患者增加一些價值。

No, thanks. And I would say a combination of all those things. I mean, as I mentioned, partly it's a learning from 004 where we recognized that not having the option for a further dose for all patients, was potentially a challenge in terms of maintaining them out for a long time, plus, we'd actually denied that as a separate study where they had to actually re-consent as opposed to integrating. But yes, clearly, from investigators as well. And I think it's very clear that understanding both durability from a single dose but also the option for retreatment. But in that continued randomized 26 weeks is information that I believe is relevant to regulators, clinicians and payers as well, of course, as patients.

不，謝謝。我會說所有這些事情的結合。我的意思是，正如我提到的，部分是從 004 中學到的，我們認識到不能為所有患者提供進一步劑量的選擇，這對於讓他們長時間保持在外可能是一個挑戰，另外，我們實際上否認這是一項單獨的研究，他們實際上必須重新同意而不是整合。但是，是的，很明顯，調查人員也是如此。而且我認為非常清楚的是，既要了解單次劑量的持久性，又要了解再治療的選擇。但在持續隨機化的 26 周中，我認為信息與監管機構、臨床醫生和付款人以及患者相關。

And our next question comes from Ritu Baral with Cowen.

我們的下一個問題來自 Ritu Baral 和 Cowen。

I wanted to ask about just some more details about Part B and Part C of 005. What is the, I guess, threshold for retreatment described in the protocol for Part B? And is it the same or different for Part C of 005? And then I've got a follow-up.

我想問的只是關於 005 的 B 部分和 C 部分的更多細節。我想，B 部分的協議中描述的再治療閾值是多少？和005的C部分是一樣的還是不一樣的？然後我有一個後續行動。

So it is -- so what we will retreat people who either do not remit or who relapse after remitting. So that is the criteria for retreatment, and there will be the option for on retreatment in Part B. Remembering that in Part B, it is in line with our original randomized assignment. So depending on what dose you were randomized to, it's the retreatment with that. And again, Part C open label will be the same thing.

就是這樣——所以我們將撤退那些不緩解或緩解後復發的人。這就是重新治療的標準，B 部分將有重新治療的選項。請記住，在 B 部分，它與我們最初的隨機分配一致。因此，根據您被隨機分配到的劑量，這就是治療。同樣，C 部分開放標籤將是同一件事。

And is there a particular MADRS threshold that defined relapse or is it a clinician discretion?

是否有一個特定的 MADRS 閾值來定義復發，還是由臨床醫生自行決定？

There is a specific one, which we haven't, at the moment, disclosed from a competitive perspective.

有一個具體的，我們目前還沒有從競爭的角度披露。

Fair enough. Okay. And then the anorexia nervosa protocol amendments. Can you describe what they were? And essentially what drove them. I think investors generally are relatively unfamiliar with this patient population. So what considerations were new to you that are very likely new to us as well?

很公平。好的。然後是神經性厭食症協議修正案。你能描述一下它們是什麼嗎？本質上是什麼驅使他們。我認為投資者通常對這個有耐心的人群比較陌生。那麼，哪些考慮因素對您來說是新的，對我們來說也很可能是新的？

No. It's a great question. Thank you. So what I would say is, I mean, that's some of those amendments are straightforward, some we're thinking more about. So I think what we learned was this is a patient population that is highly vulnerable that, in fact, the openness, the willingness to even participate in a trial is very challenging. And perhaps from the IIS, where clearly there's an element that investigators are able to work with patients, they already know.

不，這是一個很好的問題。謝謝。所以我要說的是，我的意思是，其中一些修正案是直截了當的，一些我們正在考慮更多。所以我認為我們學到的是這是一個非常脆弱的患者群體，事實上，開放性，甚至參與試驗的意願都非常具有挑戰性。也許在 IIS 中，他們已經知道，那裡顯然有一個元素，調查人員能夠與患者一起工作。

We were not fully aware of just how challenging this would be. So some of the things we're thinking about is just number of visits and scales, again, have we been over kind of -- we actually tried to get too much into that. I think that's the first thing to make sure that we can actually have screening criteria and a protocol that meets the need of some of this patient population. But I would say that we expect to continue to learn around this study as we move forward and around the challenges of working with this population.

我們並沒有完全意識到這將是多麼具有挑戰性。所以我們正在考慮的一些事情只是訪問次數和規模，再一次，我們是否有點過頭了——我們實際上試圖過多地關注它。我認為這是確保我們實際上可以擁有滿足部分患者需求的篩選標準和方案的第一件事。但我要說的是，隨著我們向前邁進以及應對與這一人群合作的挑戰，我們希望繼續圍繞這項研究進行學習。

Understood. And can you talk about -- I just wanted to be clear, you haven't actually dosed your first patient in 005, correct? And also, can you just talk about how site activation is going?

明白了。你能不能談談——我只是想澄清一下，你實際上並沒有給 005 中的第一位病人服藥，對嗎？而且，你能談談網站激活的進展情況嗎？

Yes. So you are correct. And site activation is going well. We have more than a dozen sites actually now activated for both 005 and 006. Just I remind you, we know that site activation for these studies takes a long time. It's complex, getting the individual DEA licenses, which despite all our experience, it's no quicker the second time around, unfortunately. So that is well underway. And again, we have patients in screening, but many of them need to wash out from SSRIs or whatever they're on. So the washout period is extended. But we are comfortable with where we're at, and that's why we've kind of given first the new guidance for 005 and reiterating the guidance for timing on 006.

是的。所以你是對的。網站激活進展順利。我們實際上已經為 005 和 006 激活了十幾個站點。我提醒你，我們知道這些研究的站點激活需要很長時間。這很複雜，要獲得單獨的 DEA 許可證，儘管我們有很多經驗，但不幸的是，第二次並沒有更快。所以這一切都在進行中。再一次，我們有患者在接受篩查，但他們中的許多人需要從 SSRIs 或任何他們服用的藥物中清除。所以洗脫期延長了。但我們對我們所處的位置感到滿意，這就是為什麼我們首先給出了 005 的新指導，並重申了 006 的時間指導。

And the next question is from François Brisebois and the company is Oppenheimer.

下一個問題來自 François Brisebois，公司是 Oppenheimer。

I was just wondering, you touched on after Mike's comments, Kabir, you touched on the CPT code and -- at launch and reimbursement. I was just wondering if you can add color to that because I do think it's a very important part of the story here.

我只是想知道，你在 Mike 的評論之後談到了，Kabir，你談到了 CPT 代碼，以及 - 在啟動和報銷時。我只是想知道您是否可以為其添加顏色，因為我確實認為這是這裡故事的一個非常重要的部分。

Sure. Happy to. So we recognize from the get-go that the psilocybin administration session of kind of 6 to 8 hours is essentially unprecedented. And learning also from some of what happened with Spravato around the fact that it launched from a monitoring perspective, Janssen hadn't necessarily put a comprehensive strategy towards this in place.

當然。高興。因此，我們從一開始就認識到，6 至 8 小時的裸蓋菇素給藥時間基本上是前所未有的。並且還從 Spravato 發生的一些事情中了解到，它是從監控的角度推出的，Janssen 不一定為此制定了全面的戰略。

We recognize that we actually needed to put in place a code that could potentially cover that extended administration. So the team has actually been working now for a significant period of time with the necessary professional associations, both APAs, essentially both psychiatrists and psychologists and other groups, made a submission to the AMA. We've now had 2 meetings, and I think the latest meeting in February, we're very confident that we will get that tracking code.

我們認識到我們實際上需要製定一個可能涵蓋擴展管理的代碼。因此，該團隊實際上已經與必要的專業協會合作了很長一段時間，這兩個 APA，主要是精神病學家和心理學家以及其他團體，都向 AMA 提交了意見書。我們現在已經召開了 2 次會議，我認為最近一次會議是在 2 月份，我們非常有信心我們將獲得該跟踪代碼。

Now initially, clearly, this will be a tracking code, but once it's issued, even during the conduct of the trials, we'll be able to use that to start to understand what actually the allocation of work by whom is to supporting those administration sessions. And that will allow us to build the body of evidence to turn that into a reimbursable commercial code soon after launch -- at launch or soon after. But as I said, learning from the previous experience, we recognize it was essential to have that new code in place as soon as possible. And we're confident, as I say that, that should be in the next couple of months.

最初，很明顯，這將是一個跟踪代碼，但一旦它發布，即使在進行試驗期間，我們也將能夠使用它來開始了解實際上由誰分配的工作是為了支持那些管理會議。這將使我們能夠建立證據體系，以便在發布後不久——在發佈時或發布後不久——將其轉化為可償還的商業代碼。但正如我所說，從以前的經驗中吸取教訓，我們認識到盡快制定新代碼至關重要。正如我所說，我們有信心在接下來的幾個月內完成。

Okay. And is that code related to purely the administration? Or you mentioned the word support. Is there any psychological support that could be encompassed in that -- intended in that code?

好的。該代碼是否與純粹的管理相關？或者你提到了支持這個詞。是否有任何心理支持可以包含在該準則中？

Yes. So our view is that existing codes can cover the preparation and integration sessions, which are shorter. This is for the administration session. And as you know, we define what we offer is a metapsychology support, not as therapy, because it's not directed, it's not interventional. It really is there to support the patient through the experience, but it needs to be provided by trained professionals and the code is designed to cover their services in that.

是的。所以我們的觀點是，現有規範可以涵蓋更短的準備和整合會議。這是用於管理會話。如您所知，我們將我們提供的定義為元心理學支持，而不是治療，因為它不是定向的，也不是乾預性的。它確實可以通過體驗為患者提供支持，但需要由訓練有素的專業人員提供，並且代碼旨在涵蓋他們在這方面的服務。

Okay. Great. And just lastly on that, because it's a new field, and there's a lot of unknowns here. Just to be clear, can you just talk about maybe the learnings in the past year, 2 years of looking at this in terms of the difference between psychological support and psychotherapy? And how has that evolved in terms of your thinking of the approach?

好的。偉大的。最後一點，因為這是一個新領域，這裡有很多未知數。澄清一下，您能否談談過去一年、兩年從心理支持和心理治療之間的區別來看這個問題的經驗教訓？就您對這種方法的看法而言，這是如何演變的？

So -- and this is a topic which we could dive into much longer. I think from our perspective, from the COMPASS perspective, right from the start, we have seen this as psychological support. There are things that we think are absolutely critical. Clearly, preparation, it's critical ensuring the right expectations for the patient, particularly acknowledging we're in a clinical trial setting, where there are a variety of treatments may be possible and so on.

所以——這是一個我們可以深入研究更長時間的話題。我認為從我們的角度來看，從 COMPASS 的角度來看，從一開始，我們就將其視為心理支持。有些事情我們認為絕對至關重要。顯然，做好準備，確保對患者有正確的期望至關重要，特別是承認我們處於臨床試驗環境中，可能有多種治療方法等等。

But we have always been clear that during the administration of psilocybin itself, this is around support rather than directed therapy. I'm very conscious of the fact that there is a very wide range of opinions across the community. But I think from COMPASS view, we've always been clear to use the word psychological support as opposed to psychedelic-assisted therapy and that is where our mind is.

但我們一直很清楚，在裸蓋菇素本身的給藥過程中，這是圍繞支持而不是定向治療。我非常清楚社群中存在非常廣泛的意見這一事實。但我認為從 COMPASS 的角度來看，我們一直很清楚使用心理支持這個詞而不是迷幻輔助治療，這就是我們的思想所在。

And our next question is from Patrick Trucchio with H.C. Wainright.

我們的下一個問題來自 H.C. 的 Patrick Trucchio。溫賴特。

Just a clarification on the protocol changes to the Phase III TRD program. I'm wondering if you would also need the long-term outcomes component to submit an NDA for TRD? Or would you be able to do that following the top line readouts from the 005 and 006 trials?

只是對 III 期 TRD 計劃的協議變更的澄清。我想知道您是否還需要長期結果組件來提交 TRD 的 NDA？或者您能否在 005 和 006 試驗的頂行讀數之後做到這一點？

It's a great question. And clearly, as we start the Phase III, it's a little premature to know what our regulatory strategy would be. We clearly see the primary endpoints still at 6 weeks of 005 and 006. What I will point out is that by the time we get to that primary endpoint for 006 we would actually have the entirety of 005 in hand, the full 52 weeks. And I think we will see that as a pretty robust dataset from a regulatory perspective. But more than that, I think it's premature to speculate on what exactly the dialogue with the agency would be. And of course, it's data-driven.

這是一個很好的問題。顯然，當我們開始第三階段時，現在就知道我們的監管策略是什麼還為時過早。我們清楚地看到主要終點仍在 005 和 006 的 6 週。我要指出的是，當我們到達 006 的主要終點時，我們實際上已經掌握了整個 005，即完整的 52 週。我認為從監管角度來看，我們會將其視為一個非常強大的數據集。但不僅如此，我認為現在推測與該機構的對話究竟是什麼還為時過早。當然，它是數據驅動的。

Yes. That's helpful. And I'm wondering if you can discuss whether you would intend to move ahead with a Phase II trial in COM360 in bipolar depression. And then I have a follow-up on that.

是的。這很有幫助。我想知道你是否可以討論你是否打算繼續進行 COM360 治療雙相抑鬱症的 II 期試驗。然後我對此進行了跟進。

Thank you. So we are -- like I said, I mean, the results are amazing, but it is just 14 patients and 12 out of 14 open-label single site. So we recognize that in order to really validate that we'd have to -- we are thinking around what a design would look like, what sort of control arm you would need for bipolar, what sort of size, but that thinking is right now, and it's relatively early stages.

謝謝。所以我們 - 就像我說的，我的意思是，結果是驚人的，但只有 14 名患者和 14 個開放標籤單一站點中的 12 個。所以我們認識到，為了真正驗證我們必須——我們正在考慮設計的外觀，雙極需要什麼樣的控制臂，什麼樣的尺寸，但現在的想法是正確的，而且還處於相對早期的階段。

Got it. Okay. That's helpful. And then I guess, maybe just a separate question. Just around -- there's multiple programs, of course, advancing with short-acting or short-acting mechanism of action with psychedelic agents. There's also some of the longer-acting compounds that are advancing clinical development.

知道了。好的。這很有幫助。然後我想，也許只是一個單獨的問題。就在附近——當然，有多個項目，用迷幻劑推進短效或短效作用機制。還有一些長效化合物正在推動臨床開發。

And so I'm wondering, as the space kind of builds out, how -- if you can discuss the advantages of COM360 compared to some of those other approaches, including compounds like DMT or 5-MeO-DMT. And how would you expect these advantages of COMP360 to be demonstrated in the Phase III program and some of these other trials that are now underway.

所以我想知道，隨著空間的擴大，你如何討論 COM360 與其他一些方法（包括 DMT 或 5-MeO-DMT 等化合物）相比的優勢。您如何期望 COMP360 的這些優勢在 III 期計劃和目前正在進行的其他一些試驗中得到證明。

It's a good question. And I think without -- so I mean, my fundamental response is data is what will determine where those agents are best used and so on. So like everyone, we're intrigued by some of the data that's emerging from shorter-acting, but until it's been validated in much larger studies and in particular, some of these questions around durability that we're attempting to answer in Phase III are answered by other molecules, other mechanisms, it's kind of too early to say how the field will shake out.

這是個好問題。而且我認為沒有 - 所以我的意思是，我的基本反應是數據將決定這些代理的最佳使用地點等等。因此，像每個人一樣，我們對短效藥物中出現的一些數據很感興趣，但直到它在更大規模的研究中得到驗證，特別是，我們在第三階段試圖回答的一些關於耐久性的問題是由其他分子、其他機制回答，現在說該領域將如何擺脫困境還為時過早。

But I think what we'd also say is they are very different experiences from a patient perspective. And while there is obviously a school of thought that says, by definition, shorter-acting has a, shall we say, an easier route into commercialization. I think it's way premature before we've seen data, before we understand the experience that patients have and so to know whether, in fact, duration alone is a kind of key to differentiation. So obviously, we continue to watch the space, and I'm pleased that other agents are moving forward with good data. I think that's fantastic for the field and for patients. But I think we're a long way from determining what the competitive set ultimately looks like from a patient perspective and a results perspective.

但我認為我們還要說的是，從患者的角度來看，它們是非常不同的體驗。雖然顯然有一種思想流派認為，根據定義，短效藥物有一條更容易進入商業化的途徑。我認為，在我們看到數據之前，在我們了解患者的經歷之前，要知道實際上持續時間是否是一種差異化的關鍵，還為時過早。很明顯，我們繼續關注這個空間，我很高興其他代理人正在以良好的數據向前發展。我認為這對於該領域和患者來說都很棒。但我認為，從患者的角度和結果的角度來看，我們距離確定競爭環境最終是什麼樣子還有很長的路要走。

And our next question is from Elemer Piros with EF Hutton Group.

我們的下一個問題來自 EF Hutton Group 的 Elemer Piros。

What I'd like to -- if you could clarify, please, that would there be a retreatment paradigm in Part B, both in the 005 and the 006 trials?

我想說的是——如果你能澄清一下，在 B 部分，無論是在 005 還是 006 試驗中，都會有一個撤退範式嗎？

Yes. So as we said earlier, for those who do not respond -- who after remission relapse, there is the option for retreatment in Part B. Clearly, it's the patient's choice remembering that it will be in their original assigned treatment.

是的。因此，正如我們之前所說，對於那些沒有反應的人——在緩解後復發的人，可以在 B 部分中選擇再治療。顯然，這是患者的選擇，記住這將在他們最初指定的治療中進行。

So it is true. So retreatment will occur even in the 005 trial.

所以這是真的。所以即使在005試煉中也會出現退治。

So retreatment either with 25-milligram or placebo at patient choice, yes.

因此，可以根據患者的選擇使用 25 毫克或安慰劑進行再治療。

Okay. And I think you just clarified, but I just want to make sure that I understand that even those who are not responding well would have the option to be retreated. So it's not really those who went into remission and fell out of remission.

好的。我想你剛剛澄清了，但我只是想確保我明白，即使那些反應不佳的人也可以選擇退出。所以並不是真正進入緩解期和停止緩解期的人。

Correct.

正確的。

And is this a single retreatment, Kabir?

這是一次撤退嗎，卡比爾？

Yes, yes.

是的是的。

I think I got that. And in your effort to establish a code, are you working together with MAPS in their endeavor to potentially harmonize the activities?

我想我明白了。在您努力建立準則的過程中，您是否與 MAPS 一起努力潛在地協調活動？

Yes, we are. Yes, we are. As we've said before, yes, we are working with MAPS.

是的我們是。是的我們是。正如我們之前所說，是的，我們正在使用 MAPS。

Okay. And one last question, please. When would you be able to provide an update on your internal R&D programs into other psychoactive agents?

好的。最後一個問題，請。您什麼時候能夠提供有關其他精神活性劑的內部研發計劃的最新信息？

That's a very good question. I don't know. We actually haven't landed on that, but we'll -- as you mentioned, we did say at Capital Markets Day, we would do that in due course. We'll take that internally and come back to you.

這是一個很好的問題。我不知道。我們實際上還沒有實現這一點，但我們會——正如你提到的，我們在資本市場日確實說過，我們會在適當的時候這樣做。我們會在內部處理並返回給您。

And our next question is from Neena Bitritto-Garg with Citi.

我們的下一個問題來自花旗的 Neena Bitritto-Garg。

I just have 2. So first one, just going back to the retreatment in Part B and Part C in the 005 and 006 studies. Can you just clarify, is it only at the 6-month time point, so week 26 and then week 52 in Part C that patients can go through this second or possibly third dosing session? Or could a patient be retreated earlier during Part B and Part C?

我只有 2 個。所以第一個，回到 005 和 006 研究中 B 部分和 C 部分的再治療。您能否澄清一下，是否只有在 6 個月的時間點，即 C 部分的第 26 周和第 52 週，患者才能經歷第二次或可能的第三次給藥？還是可以在 B 部分和 C 部分中更早地撤回患者？

And then my second question is just on cash and the balance sheet. It looks like you're going to end this year with maybe a couple of quarters of cash. So just curious how you're planning on dealing with the cash runway.

然後我的第二個問題只是關於現金和資產負債表。看起來您今年年底可能會有幾個季度的現金。所以很好奇你打算如何處理現金跑道。

Thanks, Neena. So yes, sorry, and I know doing this all verbally is hard. So to be clear, in Part B, the option for retreatment would be between week 6 and 26 depending on relapse or failure to respond. And then in Part C, we would expect that to be pretty early in Part C for those patients who are eligible and chose to have a COMP360 dose. So that would be soon after the start of the final 26-week open-label section.

謝謝，妮娜。所以，是的，抱歉，我知道全部口頭做這件事很難。所以需要明確的是，在 B 部分中，根據復發或反應失敗，可以選擇在第 6 周到第 26 週之間進行再治療。然後在 C 部分，對於那些符合條件並選擇接受 COMP360 劑量的患者，我們希望在 C 部分的早期。所以那將是在最後一個 26 週的開放標籤部分開始後不久。

And then on the runway, yes, so we're looking at it from a couple of perspectives, sort of the financing front and also operating moves that we could make to lengthen our runway. On the financing front, it remains a difficult market environment for financing biotech, but having said that, we have had a lot of interest from investors really since we announced the Phase III at our Capital Markets Day last fall.

然後在跑道上，是的，所以我們從幾個角度來看待它，比如融資方面以及我們可以採取的延長跑道的運營舉措。在融資方面，生物技術融資的市場環境仍然艱難，但話雖如此，自從我們去年秋天在資本市場日宣布第三階段以來，我們確實引起了投資者的極大興趣。

And it's a very serious attention from sophisticated biotech investors. So as I mentioned, it's a challenging environment, but there's still an opportunity that under the right circumstances, we could do an equity offering with those interested investors. Secondly, we do have an ATM in place. So if a new investor were to want to take up a position that's potentially a way for us to issue equity and raise cash.

這是老練的生物技術投資者非常認真的關注。所以正如我提到的，這是一個充滿挑戰的環境，但在適當的情況下，我們仍然有機會與那些感興趣的投資者進行股權發行。其次，我們確實有一台 ATM。因此，如果新投資者想要擔任職位，這可能是我們發行股票和籌集現金的一種方式。

And then lastly, there's -- I think there's an opportunity with debt. Now in the past, we've stated that we think we're a little bit early stage to be considering forms of debt, but I think in these kinds of market environments, we do have to be flexible. So under the right circumstances, that would be another way to continue to lengthen the runway of the financing.

最後，我認為債務是一個機會。現在過去，我們已經表示我們認為我們在考慮債務形式方面還處於早期階段，但我認為在這種市場環境中，我們確實必須保持靈活性。因此，在適當的情況下，這將是繼續延長融資跑道的另一種方式。

And then lastly, on the operating side, we've been very disciplined in the way that we've grown the company really since we announced the Phase II results at the end of 2021 and really have just focused on making sure we prepare and start to execute on the Phase III as well as our 2 advanced Phase II programs and really have dated all further investments on being able to continue to have a strong balance sheet and the long runway. And so those efforts will continue. And we've always said, we view our strong balance sheet as an important strategic asset, and while we want to pursue these breakthrough potential therapies, we want to do it in a way that's going to create value for our shareholders. And to date, I think we've done that pretty successfully. And that's going to be a key for us going forward.

最後，在運營方面，自從我們在 2021 年底宣布第二階段的結果以來，我們在發展公司方面一直非常有紀律，並且真的只是專注於確保我們準備好並開始執行第三階段以及我們的 2 個先進的第二階段計劃，並真正確定了所有進一步投資的日期，以便能夠繼續擁有強大的資產負債表和長跑道。因此，這些努力將繼續下去。我們一直說，我們將強大的資產負債表視為一項重要的戰略資產，雖然我們希望追求這些突破性的潛在療法，但我們希望以一種能為股東創造價值的方式進行。到目前為止，我認為我們已經非常成功地做到了這一點。這將是我們前進的關鍵。

And we have our next question from Bert Hazlett with BTIG.

BTIG 的 Bert Hazlett 提出了下一個問題。

You covered a lot of ground on this call. And I'll just ask, I think on intellectual property, if I might, on COMP360. You've talked about your protection that and patents that expire to 2038. There were a number of pending applications. Has there been any evolution with regard to IP for COMP360 or other elements that are of material importance?

你在這次電話會議上涵蓋了很多內容。我只想問，如果可能的話，我認為是關於 COMP360 的知識產權。你談到了你的保護和到期至 2038 年的專利。有許多未決的申請。 COMP360 的 IP 或其他具有重要意義的元素是否有任何進展？

Thanks, Bert. So no, nothing new to disclose here, except one note. You'll recall that 3 of our patents were challenged by another organization. That challenge was rejected. They appealed, and that appeal was also rejected in February. So that's actually the only update. We continue to be confident that we have a robust state of protection out to 2038.

謝謝，伯特。所以不，除了一張紙條外，這裡沒有什麼新東西可以透露。您會記得我們的 3 項專利受到了另一個組織的挑戰。那個挑戰被拒絕了。他們提出上訴，該上訴在 2 月也被駁回。所以這實際上是唯一的更新。我們仍然相信，我們在 2038 年之前擁有強大的保護狀態。

And our next question is from Kyle Qian with CGS.

我們的下一個問題來自 CGS 的 Kyle Qian。

This is Kyle speaking for Sumant Kulkarni. Maybe a few from us. On the open-label retreatment in the development process for that reaching a paradigm, has the company thought of doing retreatment on an as-needed basis for maybe a longer -- to a longer-term duration? And I'm curious why that has not been implemented.

我是 Kyle 代表 Sumant Kulkarni 發言。也許我們有一些。關於在達到範式的開發過程中的開放標籤撤退，公司是否考慮過根據需要進行撤退，時間可能更長——到更長期？我很好奇為什麼還沒有實施。

No. Thank you, Kyle. And when you say on an as needed, just to clarify, you're proposing multiple retreatments, yes.

不，謝謝你，凱爾。當您根據需要說，只是為了澄清，您是在提議多次撤退，是的。

Yes. For example, over like a year duration and potentially more than 1 retreatment?

是的。例如，超過一年的持續時間和可能超過 1 次的治療？

No. It's a fair question. And yes is the answer, we considered a variety of designs in terms of how we extend this out. And I think the reality is we know that our Phase III program, however, we design it, it is not going to answer all those questions to the satisfaction of all of regulators, payers, clinicians and so on as well.

不，這是一個公平的問題。答案是肯定的，我們考慮了多種設計來擴展它。我認為現實是我們知道我們的 III 期計劃，但是，我們設計它，它不會回答所有這些問題，讓所有監管機構、付款人、臨床醫生等都滿意。

Ultimately, the trade-off we arrived at was that in terms of getting clarity on durability of a single dose or potentially 2 doses in 006 and what happens with one retreatment, recognizing also that per protocol, as you'd expect, as we did in IIb, at some point, you have to allow patients to go back on to antidepressants or something because ethically, you cannot expect to sustain on without that.

最終，我們得出的權衡是，在明確 006 中單劑或可能 2 劑的持久性以及一次再治療時會發生什麼，還認識到按照方案，正如您所期望的那樣，就像我們所做的那樣在 IIb 中，在某些時候，您必須允許患者重新服用抗抑鬱藥或其他藥物，因為從倫理上講，您不能指望沒有這些藥物就可以維持下去。

So ultimately, the interpretability of multiple doses, if they're actually already on background SSRI is going to be challenging. I think in this case, with the single redose in the open label, that is again interesting data from the perspective of clinicians and so on as to the impact of that on a background about the therapy. But no, it's -- I acknowledge there are different designs we could have gone for, we think, in terms of interpretability and also balancing the needs of the different stakeholders. This was the right choice.

所以最終，多劑量的可解釋性，如果它們實際上已經在背景 SSRI 中，將具有挑戰性。我認為在這種情況下，在開放標籤中使用單次重劑量，從臨床醫生的角度來看，這又是一個有趣的數據，等等關於它對治療背景的影響。但不，它是 - 我承認我們可以採用不同的設計，我們認為，就可解釋性和平衡不同利益相關者的需求而言。這是正確的選擇。

Got it. And maybe one more. In all the non-TRD studies, such as in bipolar, anorexia nervosa or MDD, how many incidents of suicidal ideation have you observed as of to date? And what percent of total would that be?

知道了。也許還有一個。在所有非 TRD 研究中，例如雙相情感障礙、神經性厭食症或 MDD，到目前為止，您觀察到多少起自殺意念事件？佔總數的百分比是多少？

So we will have to get back to you with that data. I actually don't have this. I'm not aware of any specific finding, but I would need to come back to you with anything, particularly in the MDD study from Zurich, which I'll cover. As I remember, as I mentioned in the bipolar study, we saw none. There were no examples of that among those 14 patients. And I think Steve is reminding me that some of these are in our investor presentation.

因此，我們必須將這些數據返回給您。我其實沒有這個。我不知道有任何具體的發現，但我需要帶任何東西回來給你，特別是在蘇黎世的 MDD 研究中，我將對此進行介紹。我記得，正如我在雙極研究中提到的，我們沒有看到。在那14名患者中沒有這樣的例子。我認為史蒂夫提醒我，其中一些在我們的投資者介紹中。

And we have a follow-up question from Frank Brisebois with Oppenheimer.

我們有一個來自 Frank Brisebois 和 Oppenheimer 的後續問題。

Just a quick one here. You mentioned March 20, maybe getting feedback from the FDA in terms of your amendments. Is this something that -- on 005, is this something that you would disclose or you'll hear the feedback and adjust accordingly? Or just -- I'm just trying to figure out what we should be waiting for in terms of expectations of that date.

在這裡只是一個快速的。你提到了 3 月 20 日，可能會從 FDA 那裡得到關於你的修正案的反饋。這是什麼——在 005 上，這是你會披露的，還是你會聽到反饋並相應調整的？或者只是——我只是想弄清楚我們應該根據對那個日期的期望來等待什麼。

Yes. So as you know, I mean, typically, we have not actually disclosed the to and for of our correspondence with the FDA because, as you would expect for any Phase III company, we have a lot of to and fro including protocol amendments and so on. We recognize though that this was sufficiently significant, both in terms of 005 and the integration of the long-term follow-up that we wanted to flag it. That said, we believe that first in terms of the sizing and power of 005, ultimately, that's a sponsor decision based on our analysis of the data and what we believe around treatment difference.

是的。所以正如你所知，我的意思是，通常情況下，我們實際上並沒有披露我們與 FDA 的來往往來，因為正如你對任何 III 期公司所期望的那樣，我們有很多來回往來，包括協議修訂等在。我們認識到，無論是就 005 還是我們想要標記它的長期後續行動的整合而言，這都足夠重要。也就是說，我們認為，首先就 005 的規模和力量而言，最終，這是讚助商根據我們對數據的分析以及我們對治療差異的看法做出的決定。

And for the long-term follow-up, that's clearly aligned with the design principles that we had worked through with the FDA. So I think we do not see that as a particular clearing event, but we also wanted to acknowledge given the significance of the changes we're making, that there is a date in which they said they will get back to us with comments, if any.

對於長期跟進，這顯然符合我們與 FDA 合作的設計原則。所以我認為我們不認為這是一個特定的清理事件，但我們也想承認，鑑於我們正在進行的更改的重要性，他們說他們會在某個日期回复我們並發表評論，如果任何。

And I'm showing no further questions at this time. I would now like to turn the conference back to management for closing remarks.

我現在沒有進一步提問。我現在想把會議轉回管理層作閉幕詞。

Thank you, Amy. So thanks, everyone. Thank you very much for your participation today. Thanks for the many questions. And as always, you know where to find us, and we're always happy to take more. So thanks, everyone. Have a great day.

謝謝你，艾米。所以謝謝大家。非常感謝您今天的參與。感謝您提出的許多問題。和往常一樣，您知道在哪裡可以找到我們，而且我們總是很樂意接受更多。所以謝謝大家。祝你有美好的一天。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。