Vistagen Therapeutics Inc (VTGN) 2023 Q3 法說會逐字稿

Greetings. Welcome to VistaGen Therapeutics Third Quarter Fiscal Year 2023 Results Conference Call. (Operator Instructions) Please note, this conference is being recorded.

問候。歡迎來到 VistaGen Therapeutics 2023 財年第三季度業績電話會議。 （操作員說明）請注意，正在錄製此會議。

I will now turn the conference over to Mark Flather, Vice President of Investor Relations. Thank you. You may begin.

我現在將會議轉交給投資者關係副總裁 Mark Flather。謝謝。你可以開始了。

Thank you, Sherry. Hello, and welcome to VistaGen's conference call covering our third quarter of fiscal year 2023 financial results and a business update. Thank you for joining us today, and welcome to our stockholders, analysts and anyone taking an interest in VistaGen.

謝謝你，雪莉。您好，歡迎參加 VistaGen 的電話會議，內容涉及我們 2023 財年第三季度的財務業績和業務更新。感謝您今天加入我們，歡迎我們的股東、分析師和任何對 VistaGen 感興趣的人。

Joining me today are Shawn Singh, our Chief Executive Officer; and Jerry Dotson, our Chief Financial Officer. The format for this call will consist of prepared remarks from management, followed by a brief opportunity for questions from sell-side analysts. This call is being webcasted and will be available for replay. The link to access the replay can be found in the Investors Events section of our website, vistagen.com.

今天加入我的是我們的首席執行官 Shawn Singh；和我們的首席財務官 Jerry Dotson。此電話會議的形式將包括管理層準備好的評論，然後是賣方分析師提問的簡短機會。此電話正在網絡廣播中，可以重播。訪問重播的鏈接可以在我們網站 vistagen.com 的投資者活動部分找到。

On today's call, we will make forward-looking statements regarding our business based on our current expectations and current information. The forward-looking statements speak only as of today, and except as required by law, we do not assume any duty to update in the future any forward-looking statement made today. Of course, forward-looking statements involve risks and uncertainties, and our actual results could differ materially from those anticipated by any forward-looking statements that we may make today. Additional information concerning risks and factors that could affect our business and financial results is included in our most recent quarterly report on Form 10-Q filed earlier today with the Securities and Exchange Commission, or SEC, and in future filings that we make with the SEC from time to time, all of which are or will be available on our website and the SEC's website.

在今天的電話會議上，我們將根據我們目前的預期和當前信息對我們的業務做出前瞻性陳述。前瞻性陳述僅在今天發表，除法律要求外，我們不承擔任何義務在未來更新今天發表的任何前瞻性陳述。當然，前瞻性陳述涉及風險和不確定性，我們的實際結果可能與我們今天可能做出的任何前瞻性陳述所預期的結果存在重大差異。有關可能影響我們的業務和財務業績的風險和因素的更多信息包含在我們今天早些時候向美國證券交易委員會 (SEC) 提交的 10-Q 表格的最新季度報告中，以及我們未來向美國證券交易委員會提交的文件中不時地，所有這些都可以或將在我們的網站和美國證券交易委員會的網站上獲得。

Now I'd like to turn the call over to our Chief Executive Officer, Shawn Singh.

現在我想把電話轉給我們的首席執行官肖恩辛格。

Thank you, Mark, and good afternoon, everyone. Thank you for joining the call. There is an active and growing need for new faster-acting treatment options for anxiety and depression disorders. Treatment options without negative side effects and safety concerns that are often associated with the currently approved medicines. We remain focused on addressing the significant mental healthcare need for individuals across a broad range of demographics and in communities across the globe. Our team is committed to developing and commercializing multiple differentiated treatments that align with our mission to shift the treatment paradigm for anxiety and depression disorders and improve the trajectory of mental healthcare, One Mind at a Time.

謝謝馬克，大家下午好。感謝您加入電話會議。對焦慮症和抑鬱症的新的速效治療方案的需求日益增長。沒有負面副作用和安全問題的治療選擇通常與當前批准的藥物相關。我們仍然專注於解決全球範圍廣泛的人口統計數據和社區中個人的重大精神保健需求。我們的團隊致力於開發和商業化多種差異化治療，這些治療符合我們的使命，即改變焦慮症和抑鬱症的治療模式，並改善精神保健的軌跡，一次一個頭腦。

We'll start this call with a brief update on PH94B and our Phase III program in Social Anxiety Disorder or SAD. During the quarter, we further analyzed PALISADE-1 to obtain a better understanding of the unexpected results from that study. As a reminder, the study involved only a single dose of PH94B to subjects who were randomized to the treatment arm in the study.

我們將通過簡要更新 PH94B 和我們的社交焦慮症或 SAD III 期計劃開始本次電話會議。本季度，我們進一步分析了 PALISADE-1，以更好地了解該研究的意外結果。提醒一下，該研究僅涉及對隨機分配到研究治療組的受試者的單劑量 PH94B。

All subjects were given a highly provocative public speaking challenge conducted only in a clinical setting before a group of strangers and their change in the subjective units of distress or SUDS score was determined and measured as the primary endpoint. We move forward with this study -- the study methodology following our discussions with the FDA back in mid-2020, during the early phase of the COVID-19 pandemic, when the world was sheltered in place and social interactions and even exposure to the outside world were not encouraged.

所有受試者都接受了僅在臨床環境中在一群陌生人面前進行的高度挑釁性的公開演講挑戰，他們在痛苦的主觀單位或 SUDS 評分上的變化被確定和測量為主要終點。我們推進了這項研究——我們在 2020 年年中與 FDA 討論後的研究方法，在 COVID-19 大流行的早期階段，當時世界處於適當的庇護和社會互動，甚至暴露於外界世界沒有受到鼓勵。

Following are among the hypotheses, we believe are potential explanations for the unexpected outcomes in PALISADE-1. The study was conducted through surges of the COVID-19 pandemic, introducing significant additional variability in terms of changing social dynamics, subject stress, study site and CRO personnel turnover, mask wearing and scheduling and monitoring complexities.

以下是假設，我們認為是對 PALISADE-1 意外結果的潛在解釋。該研究是在 COVID-19 大流行期間進行的，在不斷變化的社會動態、受試者壓力、研究地點和 CRO 人員更替、口罩佩戴和日程安排以及監測複雜性方面引入了顯著的額外可變性。

Also, the public speaking challenge study design may not have been scalable to a large Phase III study, especially during the pandemic, given the various complexities of consistently administering the highly provocative challenge and requirements for rigorous adherence to the study protocol across numerous sites and over an extended period. And also, some subjects in the study may have had a reduced response to PH94B due to impaired olfactory cell function, potentially caused by the COVID-19 virus or even nasal swab testing for COVID-19 or influenza.

此外，公開演講挑戰研究設計可能無法擴展到大型 III 期研究，尤其是在大流行期間，因為持續管理高度挑釁性挑戰的各種複雜性以及在眾多地點和多個地點嚴格遵守研究協議的要求一個延長的時期。而且，研究中的一些受試者可能由於嗅覺細胞功能受損而對 PH94B 的反應降低，這可能是由 COVID-19 病毒或什至 COVID-19 或流感的鼻拭子測試引起的。

After receiving the top line results from PALISADE-1, we paused PALISADE-2, which involves the same single dose, post-randomization public-speaking challenge methodology as PALISADE-1. We then engaged independent biostatisticians to conduct an interim analysis of available data from the 140 subjects randomized in the study at that time. Based on their independent review of the unblinded data from those 140 subjects, data we've not yet seen, independent statisticians recommended that we continue PALISADE-2 as planned. Accordingly, during the quarter, we submitted protocol amendments to the PALISADE-2 study protocol to the FDA.

在收到來自 PALISADE-1 的頂級結果後，我們暫停了 PALISADE-2，它涉及與 PALISADE-1 相同的單劑量、隨機化後公開演講挑戰方法。然後，我們聘請獨立的生物統計學家對當時研究中隨機分配的 140 名受試者的可用數據進行中期分析。根據他們對來自這 140 名受試者的非盲數據的獨立審查，我們尚未看到這些數據，獨立統計學家建議我們按計劃繼續進行 PALISADE-2。因此，在本季度，我們向 FDA 提交了對 PALISADE-2 研究方案的方案修正案。

Amendments that are aimed at minimizing the potential issues that may have played a part in the unexpected results that we saw in PALISADE-1, if we decide to resume PALISADE-2, we believe these protocol changes could considerably increase the probability of favorable results in the remaining 1/3 of the trial subjects. However, a new and another important factor to note regarding our considerations for potentially resuming PALISADE-2 is that in December 2022, a couple of months ago, 2 of our peers announced top line results of their recently completed SAD studies using a single administration public-speaking challenge study design with SUDS as the primary endpoint. Neither study achieved its primary efficacy endpoint.

旨在最大程度減少可能在我們在 PALISADE-1 中看到的意外結果中發揮作用的潛在問題的修正案，如果我們決定恢復 PALISADE-2，我們相信這些協議更改可能會大大增加在 PALISADE-2 中獲得有利結果的可能性其餘1/3的試驗對象。然而，關於我們可能恢復 PALISADE-2 的考慮因素，需要注意的一個新的和另一個重要因素是，在 2022 年 12 月，也就是幾個月前，我們的 2 個同行宣布了他們最近完成的 SAD 研究的主要結果，使用單一的管理公眾- 以 SUDS 作為主要終點的口語挑戰研究設計。兩項研究均未達到其主要療效終點。

So after reviewing the information and data available to us at this time, we believe it is not yet advisable to resume PALISADE-2 before discussing our broader Phase III development plan for PH94B in SAD with the FDA and assessing the results of the other 2 recently completed SAD public-speaking challenges conducted during the pandemic that also did not achieve their primary efficacy endpoints. We remain confident in PH94B's potential to be a game changer for individuals affected by social anxiety disorders.

因此，在審查了我們此時可用的信息和數據之後，我們認為在與 FDA 討論我們針對 SAD 中 PH94B 的更廣泛的 III 期開發計劃並最近評估其他 2 項的結果之前，恢復 PALISADE-2 是不可取的完成了在大流行期間進行的 SAD 公開演講挑戰，但也沒有達到其主要療效終點。我們仍然相信 PH94B 有可能成為受社交焦慮症影響的個人的遊戲規則改變者。

We have been and will continue to explore all of our options for what we believe will be the best path forward with the highest probability of success for our Phase III program in SAD. We are currently preparing to meet with the FDA to discuss our broader Phase III development plan, which includes the possibility of conducting a multiple administration, randomized double-blind placebo-controlled Phase III study of PH94B in adults using the Liebowitz social anxiety scale, or LSAS, as the primary measure to evaluate the efficacy of PH94B over time, in patients with SAD to support a potential PH94B NDA for treatment of SAD.

我們已經並將繼續探索我們所有的選擇，我們認為這將是我們在 SAD 的 III 期項目成功可能性最大的最佳前進道路。我們目前正準備與 FDA 會面，討論我們更廣泛的 III 期開發計劃，其中包括使用 Liebowitz 社交焦慮量表對成人進行 PH94B 的多次給藥、隨機雙盲安慰劑對照 III 期研究的可能性，或者LSAS 作為評估 PH94B 隨時間推移在 SAD 患者中療效的主要指標，以支持潛在的 PH94B NDA 用於治療 SAD。

Unlike the PALISADE-1 and 2 Phase III studies, which involved assessment after only a single administration of PH94B in a clinic-based public speaking challenge, with SUDS as the primary outcome measure. The Phase III study contemplated as part of our broader plan would involve multiple administrations of PH94B on an as-needed basis up to 4 times a day in a real-world setting over multiple weeks, with the LSAS as the primary efficacy endpoint. Using the LSAS, it would be consistent with the design of all registration trials supporting the FDAs 3 precedent-setting approvals of treatments for SAD.

與 PALISADE-1 和 2 III 期研究不同，後者涉及在基於診所的公開演講挑戰中僅單次施用 PH94B 後進行評估，並將 SUDS 作為主要結果指標。作為我們更廣泛計劃的一部分所考慮的 III 期研究將涉及 PH94B 的多次管理，根據需要在現實世界環境中進行數週，每天最多 4 次，以 LSAS 作為主要療效終點。使用 LSAS，它將與支持 FDA 的 3 個 SAD 治療先例批准的所有註冊試驗的設計一致。

Given that the LSAS measures overall improvement in disease severity by measuring, both the reduction in fear and anxiety over time about social and performance situations, as well as the reduction in avoidance of those anxiety-provoking situations. We believe the LSAS is appropriate to measure and reflect the true impact of PH94B on patients' daily lives. We expect to announce our plan for PALISADE-2 concurrently with other updates to our broader PH94B Phase III development plan for SAD.

鑑於 LSAS 通過測量來衡量疾病嚴重程度的總體改善，隨著時間的推移，對社交和表現情況的恐懼和焦慮的減少，以及對那些引發焦慮的情況的迴避的減少。我們認為 LSAS 適合衡量和反映 PH94B 對患者日常生活的真實影響。我們預計將宣布我們的 PALISADE-2 計劃，同時公佈我們更廣泛的 SAD PH94B III 期開發計劃的其他更新。

Another important component of our Phase III program in SAD is the PALISADE Open Label Study, which we initiated back in October 2021 to evaluate the safety and tolerability of PH94B in adult subjects with SAD taken as needed prior to anxiety provoking social and performance situations in daily life over a period of up to 12 months. In addition to assessing safety and tolerability of PH94B in that study, we also included several exploratory objectives, including PH94B's potential to achieve overall symptom reduction and improvement in severity of SAD as measured by the LSAS. Again, it's the primary endpoint is required by the FDA for all prior SAD approvals.

我們在 SAD III 期計劃的另一個重要組成部分是 PALISADE 開放標籤研究，我們於 2021 年 10 月啟動該研究，以評估 PH94B 在患有 SAD 的成人受試者中的安全性和耐受性，該受試者在日常焦慮引發社交和表現情況之前按需服用壽命長達 12 個月。除了在該研究中評估 PH94B 的安全性和耐受性外，我們還包括了幾個探索性目標，包括 PH94B 實現總體症狀減輕和改善 SAD 嚴重程度的潛力（如 LSAS 所衡量）。同樣，這是 FDA 要求所有先前 SAD 批准的主要終點。

In August 2022, we closed recruitment and enrollment in PALISADE Open Label Study, a preliminary analysis of the final data set observing nearly 400 subjects in that study is encouraging. And although from an open label study, when considered with our prior placebo-controlled, multiple assessment Phase II study of PH94B in a real-world setting, that study has helped inform many important aspects of our broader Phase III development plan for PH94B in SAD. The open label study results reinforce our beliefs in the potential of PH94B used overtime as needed up to 4 times per day in daily life to provide rapid onset, clinically meaningful and sustained response with a favorable safety and tolerability profile. We expect to have the final data readout of observations from this study in the first quarter of calendar 2023.

2022 年 8 月，我們結束了 PALISADE Open Label Study 的招募和註冊，對觀察該研究中近 400 名受試者的最終數據集進行的初步分析令人鼓舞。儘管從一項開放標籤研究來看，當考慮到我們之前在真實環境中對 PH94B 進行的安慰劑對照、多重評估 II 期研究時，該研究有助於為我們更廣泛的 SAD PH94B III 期開發計劃的許多重要方面提供信息.開放標籤研究結果強化了我們的信念，即 PH94B 在日常生活中根據需要每天加班使用多達 4 次，以提供快速起效、具有臨床意義和持續的反應，並具有良好的安全性和耐受性。我們預計將在 2023 年第一季度從這項研究中讀出最終的觀察數據。

Moving next to our exploratory target indication for PH94B adjustment disorder with anxiety. We've completed our small Phase IIa double-blind, placebo-controlled clinical trial to evaluate the efficacy, safety and tolerability of PH94B as a potential treatment of adults with adjustment disorder with anxiety. Subjects self-administered PH94B at prescribed intervals, 4 times per day for 28 days. We anticipate announcing topline data from this exploratory Phase IIa trial by the end of the first quarter of calendar 2023.

接下來是我們針對 PH94B 焦慮調節障礙的探索性目標適應症。我們已經完成了我們的小型 IIa 期雙盲、安慰劑對照臨床試驗，以評估 PH94B 作為成人焦慮適應障礙的潛在治療方法的有效性、安全性和耐受性。受試者按規定的時間間隔自行服用 PH94B，每天 4 次，持續 28 天。我們預計將在 2023 年第一季度末公佈這項探索性 IIa 期試驗的頂線數據。

During the recent months, we achieved several milestones in our PH10 program in major depressive disorder or MDD. We submitted our U.S. IND and subsequently received the FDA's green light to conduct the Phase I randomized, double-blind, placebo-controlled safety study in healthy volunteers. That study is now underway and is intended to both confirm the favorable safety profile of PH10, establishing 3 previous clinical studies conducted in Mexico, including positive published Phase IIa study of PH10 for the treatment of MDD as well as to facilitate our plans for Phase IIb development of PH10 in the U.S. as a novel standalone treatment for MDD.

在最近幾個月裡，我們在重度抑鬱症或 MDD 的 PH10 項目中取得了幾個里程碑。我們提交了我們的美國 IND，隨後獲得了 FDA 的批准，可以在健康志願者中進行 I 期隨機、雙盲、安慰劑對照的安全性研究。該研究目前正在進行中，旨在確認 PH10 的良好安全性，建立之前在墨西哥進行的 3 項臨床研究，包括已發表的 PH10 治療 MDD 的陽性 IIa 期研究，以及促進我們的 IIb 期計劃在美國開發 PH10 作為 MDD 的新型獨立療法。

We anticipate completing that study -- Phase I study by the end of the first quarter of 2023. In all clinical studies to date, PH10 like PH94B has been well-tolerated, has not caused psychological side effects such as disassociation, hallucinations and the like or other safety concerns that may be associated with other rapid onset depression therapies such as ketamine. Also of note, we recently received the FDA's Fast Track designation for development of PH10 for MDD. Similar to the large and growing anxiety market, there is significant unmet need for patients with MDD, where the current treatments are either undesirable or inadequate.

我們預計在 2023 年第一季度末完成該研究——I 期研究。在迄今為止的所有臨床研究中，PH10 和 PH94B 一樣耐受性良好，沒有引起精神分裂、幻覺等心理副作用或其他可能與其他快速起效的抑鬱症療法（如氯胺酮）相關的安全問題。另外值得注意的是，我們最近獲得了 FDA 的快速通道指定，用於開髮用於 MDD 的 PH10。與龐大且不斷增長的焦慮症市場類似，MDD 患者的需求未得到滿足，目前的治療要么不理想，要么不充分。

With a differentiated mechanism of action that is designed to be fast-acting, non-systemic and non-sedating. We believe that PH10 has potential to shift the treatment paradigm for MDD considerably. Having PH10 in the clinic in the U.S. and under the FDA's Fast-Track designation are important recent milestones in our plan to bring PH10 to many individuals battling MDD and potentially other depression disorders.

具有差異化的作用機制，旨在快速起效、非全身性和非鎮靜作用。我們相信 PH10 有可能大大改變 MDD 的治療模式。在美國的診所和 FDA 的快速通道指定下擁有 PH10 是我們計劃將 PH10 帶給許多與 MDD 和其他潛在抑鬱症作鬥爭的人的重要里程碑。

As to AV-101, our Phase Ib drug-drug interaction clinical study with oral probenecid is ongoing. We anticipate completing that study during the second quarter of calendar 2023. After its conclusion, assuming no unexpected safety issues, we will crystallize the final components of our plan for exploratory Phase IIa development of AV-101 alone or in combination with probenecid and on our own or with a collaborator, as potential oral treatment for one or more CNS disorders involving the NMDA receptor.

至於 AV-101，我們正在進行口服丙磺舒的 Ib 期藥物相互作用臨床研究。我們預計將在 2023 年第二季度完成該研究。假設沒有意外的安全問題，我們將確定我們計劃的最終組成部分，即單獨或與丙磺舒聯合開發 AV-101 的探索性 IIa 期開發計劃自己或與合作者合作，作為涉及 NMDA 受體的一種或多種中樞神經系統疾病的潛在口服治療。

Finally, I'd like to make a few comments about our recent acquisition of Pherin Pharmaceuticals. Now that this transaction has been completed, we have full ownership of worldwide intellectual property rights to PH94Band PH10, which previously were under exclusive licenses to us from Pherin that included customary milestone and royalty payment obligations overtime. As a result of the acquisition, we've eliminated all future royalty and milestone payment obligations for PH94B and PH10, which significantly improves the potential commercial profile of these late-stage assets, should they be approved downstream. In addition, we will retain all licensing revenues, including pre-commercial licensing revenues, should we enter into such transactions as we have in the past.

最後，我想就我們最近對 Pherin Pharmaceuticals 的收購發表一些評論。現在這項交易已經完成，我們擁有 PH94Band PH10 的全球知識產權的全部所有權，這些知識產權以前是根據 Pherin 向我們授予的獨家許可，其中包括習慣性的里程碑和加班費支付義務。作為此次收購的結果，我們已經取消了 PH94B 和 PH10 的所有未來特許權使用費和里程碑付款義務，如果它們在下游獲得批准，這將顯著改善這些後期資產的潛在商業形象。此外，如果我們像過去一樣進行此類交易，我們將保留所有許可收入，包括預商業許可收入。

Further, as a result of the Pherin acquisition, we've added 3 early clinical-stage pherine product candidates to our pipeline, PH15 for cognition improvement, PH80 for migraine and hot flashes, and PH284 for appetite-related disorders. Also of note, VistaGen did not assume any debt as part of this transaction, any other liabilities from Pherin nor did we bring on any Pherin employees or take on any Pherin facilities.

此外，由於收購了 Pherin，我們在我們的產品線中增加了 3 個早期臨床階段的 pherine 候選產品，用於改善認知的 PH15，用於偏頭痛和潮熱的 PH80，以及用於食慾相關疾病的 PH284。同樣值得注意的是，VistaGen 沒有承擔任何債務作為本次交易的一部分，也沒有承擔 Pherin 的任何其他債務，我們也沒有僱傭任何 Pherin 員工或承擔任何 Pherin 設施。

I would now like our CFO, Jerry Dotson, to summarize some highlights from our financial results for the third quarter of our fiscal year 2023. Jerry?

我現在想請我們的首席財務官 Jerry Dotson 總結一下我們 2023 財年第三季度財務業績的一些亮點。Jerry？

Thank you, Shawn. As Shawn mentioned, I'd like to highlight a few of the financial results from the third quarter of our fiscal year 2023. I would also encourage everyone to review our quarterly report on Form 10-Q that we filed with the SEC earlier this afternoon for additional details and disclosures.

謝謝你，肖恩。正如肖恩提到的，我想重點介紹我們 2023 財年第三季度的一些財務結果。我還鼓勵大家查看我們今天下午早些時候向美國證券交易委員會提交的 10-Q 表季度報告了解更多詳情和披露。

During the 3 months ended December 31, 2022, we recognized $179,600 of revenue related to the AffaMed Agreement, compared to recognizing $357,900 of revenue for the 3 months ended December 31, 2021. As a reminder, the revenue recognized in both of those periods is non-cash in accordance with the applicable accounting standards. We received the related cash from AffaMed back in August of 2020.

在截至 2022 年 12 月 31 日的 3 個月內，我們確認了與 AffaMed 協議相關的收入 179,600 美元，而截至 2021 年 12 月 31 日的三個月確認的收入為 357,900 美元。提醒一下，在這兩個期間確認的收入是根據適用的會計準則，非現金。我們於 2020 年 8 月收到了 AffaMed 的相關現金。

Research and development expense decreased by $0.9 million from $7.9 million to $6.9 million for the quarters ended December 31, 2021 and 2022, respectively. This decrease is primarily due to reduced expenses related to the PALISADEs Phase III program for PH94B, which, as Shawn has described, includes PALISADE-1, PALISADE-2 and the PALISADE Open Label Study as well as the PH94B Phase IIa study in adjustment disorder with anxiety and other non-clinical development, regulatory and outsourced manufacturing activities for both PH94B and PH10. We expect R&D expense in the final quarter of our fiscal 2023 to decrease as well as we wind down these trials that Shawn has mentioned earlier.

截至 2021 年 12 月 31 日和 2022 年 12 月 31 日止的季度，研發費用分別從 790 萬美元減少 90 萬美元至 690 萬美元。這一減少主要是由於與 PH94B 的 PALISADEs III 期計劃相關的費用減少，正如 Shawn 所描述的，該計劃包括 PALISADE-1、PALISADE-2 和 PALISADE 開放標籤研究以及適應障礙的 PH94B IIa 期研究PH94B 和 PH10 的焦慮和其他非臨床開發、監管和外包製造活動。我們預計 2023 財年最後一個季度的研發費用將減少，同時我們將結束 Shawn 之前提到的這些試驗。

Our general and administrative expense was flat at approximately $3.1 million for each of the quarters ended December 31, 2022 and 2021. Our net loss attributable to common stockholders for the quarter ended December 31, 2022, was approximately $9.8 million versus a net loss of approximately $10.7 million for the quarter ended December 31, 2021. At December 31, 2022, the company had cash and cash equivalents of approximately $25.0 million.

截至 2022 年 12 月 31 日和 2021 年 12 月 31 日止的每個季度，我們的一般和行政費用持平，約為 310 萬美元。截至 2022 年 12 月 31 日止的季度，我們歸屬於普通股股東的淨虧損約為 980 萬美元，而淨虧損約為截至 2021 年 12 月 31 日的季度為 1,070 萬美元。截至 2022 年 12 月 31 日，公司擁有現金和現金等價物約 2,500 萬美元。

Again, please refer to our quarterly report on Form 10-Q filed earlier today with the SEC for additional details and disclosures. I'll now turn the call back to Shawn.

同樣，請參閱我們今天早些時候向美國證券交易委員會提交的 10-Q 表格季度報告，了解更多詳細信息和披露信息。我現在將電話轉回 Shawn。

Thanks, Jerry. We remain unwavering in our core mission to improve mental health and well-being worldwide. As we continue to advance the next stage of our corporate development, we move forward with a strong team, a strong pipeline and a strong mission that drives us to innovate better solutions for mental health disorders, all with significant unmet need. This is an exciting endeavor for our company, and we believe that we are very well positioned for 2023. On behalf of the VistaGen team, I want to thank you for the privilege and the opportunity to make a difference, One Mind at a Time.

謝謝，傑里。我們始終堅定不移地致力於改善全球心理健康和福祉的核心使命。隨著我們繼續推進公司發展的下一階段，我們將憑藉一支強大的團隊、強大的管道和強大的使命向前邁進，這些使命驅使我們為精神健康障礙創新更好的解決方案，所有這些都存在重大未滿足的需求。這對我們公司來說是一項激動人心的努力，我們相信我們已經為 2023 年做好了充分準備。我謹代表 VistaGen 團隊，感謝您給我的特權和機會，一次一個想法地改變現狀。

Thank you, Shawn. This concludes our prepared remarks. Sherry, we would like to now open the call up for questions from sell-side analysts.

謝謝你，肖恩。我們準備好的發言到此結束。雪莉，我們現在想開始徵求賣方分析師的問題。

(Operator Instructions) Our first question is from Andrew Tsai with Jefferies.

（操作員說明）我們的第一個問題來自 Jefferies 的 Andrew Tsai。

First one is that your upcoming FDA meeting, in terms of discussing a possible pivot in the Phase III design using LSAS and then multi-dosing over a long period of time. So can you kind of talk about the scenarios here if the FDA says, okay, do a pivot, what would you do with PALISADE-2? And if the FDA says no, what would you do with PALISADE-2? So basically, what I'm trying to get at is, in what scenario could we see the PALISADE-2 results at the end of the day? Even though it hasn't finished, you did see a signal in the interim analysis. So that's why I asked?

第一個是你們即將召開的 FDA 會議，討論使用 LSAS 在 III 期設計中可能的關鍵點，然後在很長一段時間內進行多次給藥。那麼，如果 FDA 說，好吧，做一個支點，你會用 PALISADE-2 做什麼，你能談談這裡的場景嗎？如果 FDA 拒絕，您將如何處理 PALISADE-2？所以基本上，我想要了解的是，在什麼情況下我們可以在一天結束時看到 PALISADE-2 結果？儘管它還沒有完成，但您確實在中期分析中看到了一個信號。所以這就是我問的原因？

Thanks, Andrew. Good question. Look, we're still -- we still have to assess really what would be the best path forward after not only we take a look further at what happened in the peer studies. So there are questions associated with scaling up that methodology and executing on was a very highly provocative challenge that requires exquisite adherence to protocol recipe. We've submitted some protocol amendments to the FDA. So we'll see what their feedback is on that, things that we think can overcome some of those methodological challenges. We'll see what their opinion is on that, as well as which direction things go in the meeting, where we're discussing a potential next step forward with LSAS as the basis, just like with the 3 approvals. So it's possible that we would simply unblind PALISADE-2 as it is and in the study there and see what we find from those unblinded data on 140 subjects, it could be denting, it could be soft trend, it could be positive signal, decent effect size, it could be a lot of things. We know what the interim analysis said, but we haven't seen the data. It's also possible of resuming PALISADE-2 depending on which direction things go with the FDA.

謝謝，安德魯。好問題。看，我們仍然 - 我們仍然必須真正評估什麼是最好的前進道路，不僅是在我們進一步了解同行研究中發生的事情之後。因此，存在與擴大該方法和執行相關的問題是一個非常具有挑釁性的挑戰，需要嚴格遵守協議配方。我們已經向 FDA 提交了一些協議修正案。因此，我們將了解他們對此的反饋，我們認為可以克服其中一些方法挑戰的事情。我們將了解他們對此的看法，以及會議的發展方向，我們正在討論以 LSAS 為基礎的潛在下一步，就像 3 項批准一樣。因此，我們有可能簡單地將 PALISADE-2 照原樣揭盲，並在那裡的研究中，看看我們從 140 名受試者的那些揭盲數據中發現了什麼，它可能是凹痕，它可能是軟趨勢，它可能是積極的信號，體面影響大小，它可能是很多東西。我們知道中期分析說了什麼，但我們還沒有看到數據。也有可能恢復 PALISADE-2，具體取決於 FDA 的發展方向。

Look, the good thing going into the discussions with the FDA is that there is a lot of evidence already, there's Phase II placebo-controlled studies in PH94B in SAD that have substantial evidence showing its rapid onset of effect following the acute administration. That was -- we talked about that study quite a bit. Then the placebo-controlled crossover study that was 2 weeks of real-world use, then that amplified by what we've seen so far, we haven't yet reported, but we'll assume observations from the long-term safety study in the LSAS component of that study in particular. So there's a lot of things to ask to the FDA. There's a lot of things to get feedback from the FDA on, and we'll make some decisions on the basis of that interaction as well as what we might learn more about. We need to do some work again with sites. We need to figure out some more information about what sites are around and are willing to be involved. And if we were going to resume, would we want changes to be made, that they may or may not be able to execute, depending on staffing and expertise. So we're set to see.

看，與 FDA 討論的好處是已經有很多證據，在 SAD 的 PH94B 中有 II 期安慰劑對照研究，有大量證據表明其在急性給藥後迅速起效。那是——我們談論了很多關於這項研究的事情。然後是安慰劑對照的交叉研究，即在現實世界中使用 2 週，然後根據我們迄今為止所看到的情況進行放大，我們尚未報告，但我們將假設來自長期安全性研究的觀察結果特別是該研究的 LSAS 部分。所以有很多事情要問 FDA。有很多事情可以從 FDA 那裡得到反饋，我們將根據這種互動以及我們可能了解的更多信息做出一些決定。我們需要再次對網站進行一些工作。我們需要弄清楚周圍有哪些站點並且願意參與其中的更多信息。如果我們要恢復，我們是否希望做出改變，他們可能會或可能不會執行，這取決於人員配置和專業知識。所以我們準備看看。

Right. Okay. Very, very helpful. And so speaking of the open label data coming up, what exactly do you plan to share with us? Basically, how much data can we expect to see in the topline release? And then secondly, part of my -- this long kind of question, but one of the issues -- underlying issues, in general, of the open label study is, there's no placebo. We don't necessarily know what the placebo would trend. That said, I can think of the epilepsy space, where there is an efficacy measure called seizure freedom because placebo can barely achieve seizure freedom in epilepsy. So that is perhaps why looking at seizure freedom rates in an OLE could make sense. So as we get back to the social anxiety space, I guess the question is, what percentage of placebo patients can achieve remission in theory over, let's just say, 6 to 12 months? Because -- and I guess, would you agree looking at remission rates could be valuable of a data point basically?

正確的。好的。非常非常有幫助。那麼談到即將到來的開放標籤數據，您到底打算與我們分享什麼？基本上，我們可以期望在頂線發布中看到多少數據？其次，我的一部分——這個很長的問題，但其中一個問題——一般來說，開放標籤研究的根本問題是，沒有安慰劑。我們不一定知道安慰劑會產生什麼趨勢。也就是說，我可以想到癲癇領域，那裡有一種稱為無癲癇發作的療效衡量標準，因為安慰劑幾乎無法使癲癇患者實現無癲癇發作。所以這也許就是為什麼在 OLE 中查看癲癇發作自由率可能有意義的原因。因此，當我們回到社交焦慮領域時，我想問題是，理論上有多少安慰劑患者可以在 6 到 12 個月內達到緩解？因為——我想，您是否同意查看緩解率基本上對數據點有價值？

So that's something we can discuss with the FDA. All of the approval studies were registrational studies for the 3 antidepressants approved for SAD. Those are all 12-week study. Again, look, we obviously acknowledge the absence of a control group in any open label study by definition. But the data from -- again, I noted this before, nearly 400 subjects observed in that study. They provide very important additional information regarding PRN dosing of PH94B. And we take that together with the data from the placebo-controlled Phase II study, where the real world study, there -- those studies provide a lot of evidence on how SAD patients would use PH94B, for example, the frequency of use in the real world setting and the appropriateness also of assessing improvement in SAD over time, utilizing the LSAS, obviously, as the key measurement. For that, given that, that's the historical precedent, that's the historical compare to 3 of them now. So we know each SAD patient is different. We know SAD treatment is individualized and tailored to the situations that patients encounter in their daily life.

所以這是我們可以與 FDA 討論的事情。所有批准研究都是針對 SAD 批准的 3 種抗抑鬱藥的註冊研究。這些都是為期 12 週的學習。再一次，看，我們顯然承認在定義的任何開放標籤研究中都沒有對照組。但是數據來自——再次，我之前註意到了這一點，在該研究中觀察了近 400 名受試者。它們提供了關於 PH94B 的 PRN 劑量的非常重要的附加信息。我們將其與安慰劑對照 II 期研究的數據結合起來，那裡是真實世界的研究——這些研究提供了大量關於 SAD 患者如何使用 PH94B 的證據，例如，在現實世界的設置以及隨著時間的推移評估 SAD 改善的適當性，顯然，利用 LSAS 作為關鍵衡量標準。為此，鑑於此，這是歷史先例，這是與現在其中 3 個的歷史比較。所以我們知道每個 SAD 患者都是不同的。我們知道 SAD 治療是根據患者在日常生活中遇到的情況進行個性化和量身定制的。

We think PRN use is the most appropriate dosing strategy for the treatment of SAD unlike the single highly provocative administration assessment that was in the PALISADE-1 and PALISADE-2 studies. And that these feared situations that people encounter, they are very predictable and are awaited with fearful and anxious anticipation. So the LSAS, which again, long established by Dr. Liebowitz, who's the PI of the Phase II studies and also currently working with us, that remains the most appropriate outcome measure for the type of study we might next do, right, a double-blind, placebo-controlled study that evaluates the efficacy of as needed use of PH94B, but overtime for the treatment. Because what we're trying to essentially do is reset the mind, similar to how cognitive behavioral therapy works. And rather than taking, say a snapshot with studs and with the public speaking challenge, they all assess more like a movie, assessing the improvement of the patient over time. And again, having those -- having the LSAS is the primary endpoint is consistent with the registrational trials for the existing approved treatment. So it may be prudent, as you said, to follow beyond 12 weeks. We know this is a chronic disorder.

我們認為使用 PRN 是治療 SAD 最合適的劑量策略，這與 PALISADE-1 和 PALISADE-2 研究中的單一高度激發給藥評估不同。人們遇到的這些可怕情況是可以預見的，人們懷著恐懼和焦慮的期待等待著他們。因此，LSAS 再次由 Liebowitz 博士長期建立，他是 II 期研究的 PI，目前也與我們合作，它仍然是我們接下來可能進行的研究類型的最合適的結果測量，對，雙-盲法、安慰劑對照研究，評估按需使用 PH94B 的療效，但治療超時。因為我們試圖做的本質上是重置思維，類似於認知行為療法的工作原理。而不是拍攝，比如用螺柱和公開演講挑戰拍攝快照，他們都更像電影一樣評估，評估患者隨著時間的推移而改善。再一次，擁有那些 - 擁有 LSAS 是主要終點與現有批准治療的註冊試驗一致。因此，正如您所說，追踪超過 12 周可能是謹慎的做法。我們知道這是一種慢性疾病。

So repeat dosing is exactly the way we've long envisioned using PH94B to help people. And again, a lot of the reason we moved into the PALISADE-1 was where the world was at the time, in the middle of 2020 when we last met with the agency about Phase III study design that you couldn't even go outside as you all remember. So exposing people to stressors over a long period of time, 6 weeks was probably what we would see in a Phase III study, given the way that PH94Bs onset is rapid, what we would see say in the 6-week study would be really what the antidepressants achieved in a 12-week period, since they have a long onset of action.

因此，重複給藥正是我們長期以來設想的使用 PH94B 幫助人們的方式。再一次，我們進入 PALISADE-1 的很多原因是當時的世界，在 2020 年年中，當我們最後一次與該機構就 III 期研究設計會面時，你甚至不能出門你們都記得。因此，讓人們長時間暴露在壓力源下，6 周可能是我們在 III 期研究中看到的，考慮到 PH94B 起效很快，我們在 6 週研究中看到的實際上是什麼抗抑鬱藥在 12 週內取得了成功，因為它們起效時間長。

So what we would show to your first part is, we would certainly want to show improvement on the LSAS at least 1 month and probably 2 month given that we're aiming for a study design somewhere in the 4- to 6-week range. So what we're looking for there is, are we seeing a significant drop. Again, this is observed data. We understand how the control group, but it definitely informs when you have nearly 400 subjects. It gives us a lot of information to tack on top of really the other crossroad we were at back in 2020. We could have gone to the real-world study then, but for the fact that we're in COVID. And now I think we have that opportunity given that the world settled down a bit, vaccines are okay, and we have a lot more understanding of the safety associated with having people record their stressful events and having LSAS assessments for a long period of time.

因此，我們要向您展示的第一部分是，鑑於我們的目標是在 4 到 6 週範圍內的某處進行研究設計，我們當然希望至少在 1 個月甚至 2 個月內展示 LSAS 的改進。所以我們正在尋找的是，我們是否看到了顯著下降。同樣，這是觀察到的數據。我們了解對照組的情況，但當您有近 400 名受試者時，它肯定會告知。它為我們提供了很多信息，可以幫助我們在 2020 年真正處於另一個十字路口之上。那時我們本可以進行真實世界的研究，但因為我們處於 COVID 中。現在我認為我們有這個機會，因為世界已經安定下來，疫苗還可以，而且我們對讓人們記錄他們的壓力事件和長期進行 LSAS 評估的安全性有了更多的了解。

Right. Last one and then I'll hop in the queue is, on the adjustment disorder data coming up, it is also dosed chronically placebo-controlled 40 subjects, I believe. So I think the primary endpoint is day 20 HAM-A scores. So can you kind of give us a reminder what existing drugs show at 4 weeks, just so we can have a comparator when that data comes?

正確的。最後一個，然後我要加入隊列的是，關於即將出現的調整障礙數據，我相信它也長期服用安慰劑對照的 40 名受試者。所以我認為主要終點是第 20 天的 HAM-A 分數。那麼，您能否提醒我們現有藥物在 4 週時的表現，這樣我們就可以在數據出現時進行比較？

Yes. Not a lot of competitors. That's a challenge with this disorder. It's in DSM-5, but there really aren't a lot of controlled studies. That's why this really lands in exploratory study zone. HAM-A, you had to have somewhere around 20 to be enrolled and people had to be on if they were on anything, there were stable background antidepressants, but -- we'll -- it's an exploratory study. It's a small study, as you said, around 40 subjects. We're looking for a signal, as you'd expect from a IIa study. It's not heavily powered as you'd expect with the exploratory design. So we'll see. The 300 meds are used. But unfortunately, they're just -- it's the same sort of collection of meds that we see in social anxiety disorder that folks that had never really had experience with anxiety, but for, in most cases, something here associated with the chaos, the domino effect from COVID, job loss, relationship loss, isolation, those things started to impair their functioning. That's adjustment disorder and anxiety that disrupted routines and so forth. So benzos, beta blockers, antidepressants, alcohol, all kinds of things that really aren't optimal for SAD or also not optimal for adjustment disorder.

是的。競爭對手不多。這是這種疾病的挑戰。它在 DSM-5 中，但實際上並沒有很多對照研究。這就是為什麼它真正落在探索性研究區的原因。 HAM-A，你必須有大約 20 人才能註冊，如果人們在服用任何東西，他們必須服用，有穩定的背景抗抑鬱藥，但是 - 我們會 - 這是一項探索性研究。正如您所說，這是一項小型研究，大約有 40 個受試者。正如您對 IIa 研究的期望，我們正在尋找信號。它不像您對探索性設計所期望的那樣強大。所以我們拭目以待。使用了300種藥物。但不幸的是，它們只是——這是我們在社交焦慮症中看到的同一種藥物集合，那些從未真正經歷過焦慮的人，但在大多數情況下，這裡與混亂有關的東西， COVID 帶來的多米諾骨牌效應、失業、失去關係、孤立，這些事情開始損害他們的功能。那是擾亂常規的適應障礙和焦慮等等。因此，苯並類藥物、β 受體阻滯劑、抗抑鬱藥、酒精，所有這些對 SAD 都不是最佳選擇或者對調節障礙也不是最佳選擇的東西。

Thanks, Shawn. Appreciate that progress.

謝謝，肖恩。欣賞這一進步。

Our next question is from Tim Lugo with William Blair.

我們的下一個問題來自 Tim Lugo 和 William Blair。

For the upcoming adjustment disorder study, can you remind me how many doses these patients are taking per day? And I guess, following up with the prior question, do you have a sense of what the placebo rate is in this setting? I guess there's any sort of historical that you can compare to?

對於即將進行的適應障礙研究，您能提醒我這些患者每天服用多少劑量嗎？我想，在回答前面的問題之後，您是否了解這種情況下的安慰劑率是多少？我想有什麼歷史可以比較？

Yes. I'll take that part first, Tim. There's just isn't a lot of traffic historically in this disorder. And so I can't really give you a well-grounded number. In terms of the dosing regimen, we had, again, a [talk support] early on showed a lot of safety from PH94B taken up to 4 times a day. So we sort of force that into this exploratory study. There wasn't a lot grounded that necessarily said 4x is what was needed. But part of it was to also establish safety associated with taking the drug 4 times a day because that crosses over into thoughts about safety related to taking PH94B, 4 times a day in multiple different SAD related anxiety-provoking episode. So there was a little bit of crossover intention by that study regimen. So in this one, it's 4 times a day. It's recommended to be spaced out an hour or so between doses in morning, early -- late morning, early afternoon and evening, so 4x is kind of spread out for an hour so in between. We know PH94B has a rapid onset. We also know it has a fairly short duration of effect. So that's part of the benefit of it being sort of a better benzo without the baggage, right, rapid onset, but without the lingering cognitive impairment. So it's 4 times a day split by a few hours over 28 days.

是的。提姆，我先來做這部分。從歷史上看，這種疾病的交通量並不多。所以我真的不能給你一個有根據的數字。在給藥方案方面，我們再次獲得了早期的[談話支持]，表明每天服用 4 次 PH94B 非常安全。因此，我們將其強加到這項探索性研究中。沒有太多根據可以說需要 4 倍。但其中一部分也是為了確定與每天服用 4 次藥物相關的安全性，因為這會涉及與服用 PH94B 相關的安全性想法，每天 4 次在多個不同的 SAD 相關的焦慮發作中。因此，該研究方案有一點交叉意圖。所以在這個中，它是一天 4 次。建議在早上、清晨、傍晚、下午和晚上的劑量之間間隔一個小時左右，所以 4x 有點分散在一個小時之間。我們知道 PH94B 起效迅速。我們也知道它的作用持續時間相當短。所以這是它作為一種更好的苯並沒有包袱的好處的一部分，正確的，快速起效，但沒有揮之不去的認知障礙。所以在 28 天內一天 4 次，分成幾個小時。

Okay. That's helpful. And so outside of the upcoming PH94B meeting, it sounds like you got a couple of assets through the Pherin acquisition, PH80 specifically. Can you just -- outside of PH94B, can you rank kind of where the rest of the pipeline is in terms of priorities for the company?

好的。這很有幫助。因此，在即將舉行的 PH94B 會議之外，聽起來您通過收購 Pherin 獲得了一些資產，特別是 PH80。你能不能——在 PH94B 之外，你能根據公司的優先事項對其餘管道的位置進行排序嗎？

Yes, sure. Well, PH94B, of course, way top of the list and across multiple indications in the 2 that we've acted on in the clinic SAD and adjustment disorder, PH10 following right after that. We have a IIa that was done outside the U.S. That's the POC study for that asset in major depressive disorder. We had to bring it back to the U.S. to a full IND enabling program, optimize the formulation a bit. The small Phase I that we're doing should be done here within a few months, and we'll announce on that probably early second quarter. That then lets us hopefully move right back into late-stage Phase IIb development with that asset as a standalone treatment option for MDD with the rapid onset and the same similar features in terms of no systemic uptake and to sedation is PH94B. And then it's kind of leveled out. There are early -- there's early clinical data for PH15, P80 and PH284 done again outside the U.S. in most cases and some cases here. But we're going to need to do some IND-enabling work for those 3 assets, similar to what we had to do for PH10. We expect to be able to achieve some grant support for that work. That was non-clinical work that gets us back into the clinic.

是的，當然。嗯，PH94B，當然，在我們在臨床 SAD 和適應障礙中採取行動的 2 個中的多個適應症中名列前茅，緊隨其後的是 PH10。我們有一項 IIa 是在美國以外進行的。這是針對重度抑鬱症資產的 POC 研究。我們必須將它帶回美國，以進行完整的 IND 支持計劃，稍微優化一下配方。我們正在做的第一階段應該會在幾個月內在這裡完成，我們可能會在第二季度初宣布。然後讓我們有希望回到後期階段的 IIb 開發，該資產作為 MDD 的獨立治療選擇，具有快速起效和相同的類似特徵，沒有全身吸收和鎮靜是 PH94B。然後它有點趨於平穩。有早期 - 在大多數情況下和一些情況下，PH15、P80 和 PH284 的早期臨床數據在美國境外再次完成。但我們將需要為這三項資產做一些 IND 支持工作，類似於我們為 PH10 所做的工作。我們希望能夠為這項工作獲得一些贈款支持。那是讓我們回到診所的非臨床工作。

AV-101, we see probably more advanced than PH80, PH15 and PH284 at this point, because if we seen the safety that we're hoping with this combination, we have a lot of preclinical data, really solid preclinical data across a few indications involved in the NMDA receptor. So levodopa-induced dyskinesia, neuropathic pain, some of the models that we've done in MPTP monkeys as well as in models for pain against Lyrica and gabapentin, so we'll have to decide which direction we want to go. But I think the IIa would be the next priority after PH10 for IIb with AV-101 and then we'll see how things go. We haven't had our hands on the new Pherin assets for too long. So we want to do a little more digging into the data sets that exist. But there are data, clinical data across all those that are fairly encouraging, and we just need to get more direct touch on all 3 of those as we see what we might want to do there. There's a lot of grant opportunities for those assets. The core focus, however, predominantly is on PH94B followed then by PH10.

AV-101，我們目前看到的可能比 PH80、PH15 和 PH284 更先進，因為如果我們看到我們希望這種組合的安全性，我們有很多臨床前數據，非常可靠的幾個適應症的臨床前數據參與 NMDA 受體。因此，左旋多巴引起的運動障礙、神經性疼痛、我們在 MPTP 猴子以及針對 Lyrica 和加巴噴丁的疼痛模型中所做的一些模型，所以我們必須決定我們想要走的方向。但我認為 IIa 將是 PH10 之後的下一個優先級，用於帶有 AV-101 的 IIb，然後我們將看看事情的進展。我們已經太久沒有接觸到新的 Pherin 資產了。所以我們想對現有的數據集做更多的挖掘。但是所有這些數據、臨床數據都相當令人鼓舞，我們只需要更直接地接觸所有這三個數據，因為我們看到了我們可能想在那裡做的事情。這些資產有很多贈款機會。然而，核心重點主要放在 PH94B 上，然後是 PH10。

(Operator Instructions) And we do have a follow-up question from Andrew Tsai with Jefferies.

（操作員說明）我們確實有來自 Jefferies 的 Andrew Tsai 的後續問題。

So speaking of the PH94B, you did mention earlier some competitors reported some SAD topline data. My understanding is one of the competitors did, in fact, see a signal when they -- depending on how they analyze the data, they'll talk to the FDA is how I understand it. So I guess the question is, if the FDA buys into their SUDS and long-story short, whereas the FDA buys into your LSAS, let's just say that scenario happens, how do you guys decide to proceed because I presumably, you would have 2 options to go with here?

所以說到 PH94B，你之前確實提到了一些競爭對手報告了一些 SAD 頂線數據。我的理解是其中一個競爭對手確實看到了一個信號——這取決於他們如何分析數據，他們會告訴 FDA 是我的理解方式。所以我想問題是，如果 FDA 購買了他們的 SUDS 和長話短說，而 FDA 購買了你們的 LSAS，那麼假設這種情況發生了，你們如何決定繼續進行，因為我想，你們會有 2與這裡一起去的選項？

We already know where the FDA is on SUDS. There's no question about that. It's a valid endpoint. That is, the public speaking challenge is a solid methodology. I have no issues about either of those. The question is, can you scale it effectively and into the size of a study that's necessary to be a registrational study. And that's what we're trying to assess at the moment, right? We know the challenges that are associated with the protocol, with the methodology that it was -- for example, do you -- is it the surveillance to whether or not you have the right raters that are changed as you move from the different visits, making sure that people don't inhale the drug, making sure that people haven't destroyed the cells associated with where we need the drug the land. There's a lot of things that land on that one single administration assessment. And it's a very provocative trigger. I mean, those Phase II studies that the peers did their Phase II study. So it's a whole different ball game when you move into scaling that methodology up to the size and quality necessary to support a registration study. And that's what we're assessing. It may be possible with the changes we proposed to the FDA or it may be something that we say just isn't -- isn't worth that risk? And isn't necessary?

我們已經知道 FDA 在 SUDS 上的位置。毫無疑問。這是一個有效的端點。也就是說，公開演講挑戰是一種可靠的方法論。我對其中任何一個都沒有問題。問題是，您能否有效地將其擴展到註冊研究所需的研究規模。這就是我們目前正在嘗試評估的，對吧？我們知道與協議相關的挑戰，以及它的方法 - 例如，你 - 是否有監督你是否有正確的評分員，隨著你從不同的訪問中轉移，確保人們不會吸入藥物，確保人們沒有破壞與我們需要藥物的地方相關的細胞。有很多事情落在一個單一的管理評估上。這是一個非常挑釁的觸發器。我的意思是，那些同行進行的 II 期研究。因此，當您開始將該方法擴展到支持註冊研究所需的規模和質量時，情況就完全不同了。這就是我們正在評估的。我們向 FDA 提出的更改可能是可能的，或者它可能是我們所說的不是——不值得冒這個風險嗎？而且沒有必要？

If PALISADE-2 at the end of the day goes all the way and what we end up having is a positive signal with a good effect size, but it's not statics. Well, then that isn't going to support an NDA. If we think that there is going to be rigorous adherence to the protocol with the sites that would be involved that the macro environment would be right. Those all go into the sinking. But the fact it's very unusual for 3 studies with the same methodology, but distinct drugs within a 6-month period of time would not hit their primary endpoint, statics on their primary endpoint. So it's just that's part of our thinking.

如果 PALISADE-2 在一天結束時一路走來，我們最終得到的是一個具有良好效果大小的積極信號，但這不是靜態的。好吧，那不會支持 NDA。如果我們認為涉及的站點將嚴格遵守協議，那麼宏觀環境就是正確的。那些都進入下沉。但事實是，使用相同方法的 3 項研究非常不尋常，但在 6 個月的時間內不同的藥物不會達到他們的主要終點，主要終點的靜態。所以這只是我們想法的一部分。

The other side of it is, as to the LSAS, a, we know there's historical comparators there. There are -- although, we don't think there's a regulatory risk with SUDS, based on our prior interactions with the agency, there is -- there are 3 historical comparators that support LSAS as the primary endpoint for all 6 registration studies. All of the registration studies, by the way, for SAD using the LSAS, all of them were positive. That's big positive, not a single one wasn't. So that says a lot as well, right, in terms of downstream, risk assessment, discipline use the cash and resources, we'll just have to make a decision about what's the best way to put time, talent and cash towards ultimately what we want. We want an NDA that is approved. We want study designs that fit the way we think the drug best fits, how we think people can be helped by it in the world. So there is a lot of confidence behind the -- if you look at those same drugs in depression paxil, zoloft effects are -- there were a steady string of successes. There were multiple failures and multiple successes.

另一方面，關於 LSAS，a，我們知道那裡有歷史比較器。有——儘管我們認為 SUDS 不存在監管風險，根據我們之前與該機構的互動，有——有 3 個歷史比較器支持 LSAS 作為所有 6 項註冊研究的主要終點。順便說一下，所有使用 LSAS 的 SAD 註冊研究都是陽性的。這是一個很大的積極因素，沒有一個不是。所以這也說明了很多，對，在下游、風險評估、紀律使用現金和資源方面，我們只需要決定什麼是將時間、人才和現金投入到我們最終目標的最佳方式想。我們想要獲得批准的 NDA。我們希望研究設計符合我們認為藥物最適合的方式，我們認為世界上人們可以從中得到幫助的方式。所以背後有很大的信心——如果你看看抑鬱症帕西爾中的那些相同的藥物，唑洛夫特的效果是——有一連串的成功。有多次失敗和多次成功。

But interestingly, in SAD for the registrational studies, all were positive and all use only to LSAS as the primary efficacy end point. So with a bit of a changed world now, where COVID's under control and a lot of other factors that we would improve on that some lessons learned from PALISADE-1 that transport into what we would do if the direction forward is a Phase III study with LSAS as the primary. The odds set pretty nicely.

但有趣的是，在註冊研究的 SAD 中，所有結果都是陽性的，並且都只使用 LSAS 作為主要療效終點。因此，現在世界發生了一些變化，在 COVID 得到控制的情況下，還有許多其他因素我們可以改進，從 PALISADE-1 中吸取的一些經驗教訓將轉化為如果前進方向是 III 期研究，我們將做的事情LSAS 為主。賠率設置得很好。

Right. Last question then is if you -- ultimately, if you do proceed with LSAS, how fast can you get to Phase III studies up and running and having generated the data? Can you kind of walk us through the time lines?

正確的。那麼最後一個問題是，如果你——最終，如果你確實繼續使用 LSAS，你能多快啟動和運行 III 期研究並生成數據？你能給我們介紹一下時間線嗎？

Yes. Well, of course, a lot of it depends on funding, right? Right now, we're not sitting on funding that supports all the way through those data readouts. But in an optimal scenario, we would be in a mode in about 6 months, it takes to get going for the type of study that we want to launch with the sites, we would want to be involved and now we've been involved with now around almost 40 sites across the 2 studies. We know the landscape very well. SAD is back in motion as something that's being studied it hadn't really been before we brought it back with PALISADE-1. So those studies, if we would start them sometime before the end of the year, we could see readouts in the fourth quarter of '24. And it'd be a staggered start again, 2 studies running in parallel, both a little bit of a staggered start as we did with PALISADE-1, PALISADE-2, the LSAS based studies would run next to each other. And we think we could see readouts by the end of the fourth quarter of '24 if we get going here within the next several months.

是的。好吧，當然，很多都取決於資金，對吧？現在，我們並沒有坐擁所有支持這些數據讀出的資金。但在最佳情況下，我們將在大約 6 個月內進入一種模式，這需要開始我們想要在網站上啟動的研究類型，我們希望參與其中，現在我們已經參與了現在，這 2 項研究涉及近 40 個站點。我們非常了解風景。 SAD 作為正在研究的東西重新啟動，在我們用 PALISADE-1 將它帶回來之前並沒有真正研究過。所以那些研究，如果我們在今年年底之前的某個時候開始，我們可以在 24 年第四季度看到讀數。這又將是一個交錯的開始，2 項研究並行進行，就像我們對 PALISADE-1、PALISADE-2 所做的那樣，兩者都有一點交錯的開始，基於 LSAS 的研究將彼此相鄰進行。我們認為，如果我們在接下來的幾個月內開始，我們可以在 24 年第四季度末看到讀數。

Great. All right. Thanks again for taking these questions. Very helpful.

偉大的。好的。再次感謝您提出這些問題。很有幫助。

There are no further questions at this time.

目前沒有其他問題。

Thanks so much. If you have any additional questions, please do not hesitate to get in touch with us by emailing ir@vistagen.com or contacting the individuals listed on our press release issued today. We are also -- and we also encourage you to sign up on our website to stay connected with the latest news from VistaGen. Thank you for tuning in and we appreciate everyone's attention and support. We look forward to keeping you current on our continuing progress. This concludes our call. Have a great day. You may all disconnect.

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