Vistagen Therapeutics Inc (VTGN) 2024 Q2 法說會逐字稿

Good day, everyone, and welcome to today's Vistagen fiscal year 2024 second quarter corporate update conference call. (Operator Instructions) Please note this call is being recorded. I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Mark McPartland. Please go ahead, sir.

大家好，歡迎參加今天的 Vistagen 2024 財年第二季企業更新電話會議。 （操作員說明）請注意此通話正在錄音。如果您需要任何幫助，我將隨時待命。現在我很高興將會議交給馬克·麥克帕特蘭。請繼續，先生。

Thank you, Travis. Good afternoon, everyone, and welcome to Vistagen's fiscal year 2024 second quarter corporate update conference call and webcast. This afternoon, we filed our quarterly report and issued a press release providing an overview of our progress last quarter. We encourage you to review the release, which can be found on the Investors section of the Vistagen website.

謝謝你，崔維斯。大家下午好，歡迎參加 Vistagen 2024 財年第二季企業更新電話會議和網路廣播。今天下午，我們提交了季度報告並發布了新聞稿，概述了我們上個季度的進展。我們鼓勵您查看新聞稿，您可以在 Vistagen 網站的投資者部分找到該新聞稿。

During today's call, we will make forward-looking statements regarding our business based on our current expectations and information. 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.

在今天的電話會議中，我們將根據我們目前的預期和資訊對我們的業務做出前瞻性陳述。前瞻性陳述僅代表今天的情況，除非法律要求，否則我們不承擔任何責任在未來更新今天做出的任何前瞻性陳述。

Of course, forward-looking statements involve risks and uncertainties, and our actual results could differ materially from those anticipated by any forward-looking statements we make today. Additional information concerning risks, factors that could affect our business and financial results is included in our fiscal year 2024 second quarter Form 10-Q for the period ending September 30, 2023, and in future filings that we will make with the SEC from time to time, all of which are or will be available on our website and the SEC's website.

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所做的任何前瞻性陳述的預期有重大差異。有關風險、可能影響我們業務和財務表現的因素的更多資​​訊包含在截至2023 年9 月30 日期間的2024 財年第二季度10-Q 表中，以及我們將不時向SEC 提交的未來文件中。時間，所有這些都已經或將在我們的網站和 SEC 網站上提供。

With that taken care of, I'd like to thank and welcome all of our stockholders, analysts, and everyone, taking an interest in Vistagen. I'm joined on the call today by Shawn Singh, our Chief Executive Officer; Cindy Anderson, our Chief Financial Officer; and Josh Prince, our Chief Operating Officer.

考慮到這一點，我要感謝並歡迎我們所有的股東、分析師和每個對 Vistagen 感興趣的人。我們的執行長肖恩辛格 (Shawn Singh) 也加入了我今天的電話會議。辛蒂‧安德森 (Cindy Anderson)，我們的財務長；和我們的營運長喬許‧普林斯 (Josh Prince)。

Shawn will provide an overview on the recent results and our progress across our key pipeline programs. A brief opportunity for questions from our sell-side analysts will follow the prepared remarks. This call is being webcast and will be available for replay after completion. The replay link can be found in the Investor Events section of our website.

肖恩將概述最近的結果以及我們在關鍵管道項目上的進展。在準備好的發言之後，我們的賣方分析師將有一個簡短的提問機會。該電話會議正在網路直播，結束後可重播。重播連結可以在我們網站的投資者活動部分找到。

I would now like to turn the call over to our Chief Executive Officer, Shawn Singh.

我現在想將電話轉給我們的執行長肖恩辛格 (Shawn Singh)。

Thank you, Mark, and good afternoon, everyone, and thank you for joining our call. We achieved several milestones since our last call to establish a well-defined and fully funded Phase 3 development program of our lead pherine asset, fasedienol, with the potential to enable us to advance to appeal to a potential NDA submission for the acute treatment with social anxiety disorder.

謝謝馬克，大家下午好，謝謝您加入我們的電話會議。自從上次呼籲為我們的主要費林資產fasedienol 建立一個明確且資金充足的第3 階段開發計劃以來，我們取得了幾個里程碑，這有可能使我們能夠提前呼籲潛在的新藥申請提交，用於急性治療與社會焦慮症。

In the midst of the ongoing mental illness crisis, we are poised to transform the treatment paradigm for this widespread anxiety disorder that affects the lives of about 10% of our population. Social anxiety disorder or SAD is a disruptive serious and potentially life-threatening anxiety disorder with high opportunity cost in daily life and no FDA approved patient tailored as needed acute treatment option to help individuals rapidly and safely address their anxiety when the stresses are upon them during what for many is their decades long journey with SAD.

在持續的精神疾病危機中，我們準備好改變這種廣泛存在的焦慮症的治療模式，影響著我們約 10% 人口的生活。社交焦慮症（SAD）是一種破壞性的、嚴重的、可能危及生命的焦慮症，在日常生活中具有很高的機會成本，FDA 還沒有批准根據患者需要量身定制的急性治療方案，以幫助個人在生活中面臨壓力時快速、安全地解決焦慮問題。對許多人來說，這是他們數十年來與 SAD 的鬥爭。

The hope of a revolutionary approach to treatment extends beyond fasedienol and SAD to our full pherine-based-portfolio, and we remain fully focused on their development to create faster-acting, safer alternatives to address significant unmet needs in large CNS-related markets where current treatment options fall short for patients.

革命性治療方法的希望不僅限於fasedienol 和SAD，還包括我們基於苯丙胺酸的完整產品組合，我們仍然完全專注於它們的開發，以創造更快、更安全的替代品，以滿足大型中樞神經系統相關市場中未滿足的重大需求。目前的治療方案不足以滿足患者的需求。

Since our last conference call in August, we've continued to build on the momentum created by our successful PALISADE-2 Phase 3 study of fasedienol for the treatment of anxiety in adults with social anxiety disorder.

自 8 月上次電話會議以來，我們繼續利用我們成功的 PALISADE-2 第 3 期研究所創造的勢頭，研究 fasedienol 用於治療患有社交焦慮症的成年人的焦慮。

During the past few months, we've strengthened our balance sheet considerably, securing $137.7 million in gross proceeds from equity financings and exclusive negotiation agreement with Fuji Pharma regarding a potential license to develop and commercialize our PH80 in Japan. We expect this cash infusion will extend our corporate runway through several important clinical and corporate milestones as we advance our pipeline, including our primary focus on a potential US new drug application or NDA for fasedienol in SAD.

在過去的幾個月裡，我們大大增強了我們的資產負債表，透過股權融資以及與富士製藥就在日本開發和商業化 PH80 的潛在許可達成的獨家談判協議獲得了 1.377 億美元的總收益。我們預計，隨著我們推進產品線，這筆現金注入將透過幾個重要的臨床和企業里程碑來擴展我們的企業跑道，包括我們主要專注於潛在的美國新藥申請或用於 SAD 的 fasedienol 的 NDA。

Given that fasedienol's rapid onset mechanism of action is differentiated from all FDA approved anxiety drugs. Our primary target initial indication for fasedienol remains the acute treatment of anxiety in adults with SAD. And as noted, there's no FDA approved drug therapy for the acute treatment of SAD.

鑑於 fasedienol 的快速起效作用機制不同於 FDA 批准的所有焦慮藥物。我們對 fasedienol 的主要目標初始適應症仍然是急性治療 SAD 成人焦慮症。如上所述，目前尚無 FDA 核准的藥物療法可用於 SAD 的急性治療。

For that acute indication, we've previously aligned with the FDA that a simulated public speaking challenge in a clinical setting is an appropriate study design and that the subjective units of distress scale or SUDS is an appropriate primary efficacy endpoint to assess the efficacy of fasedienol because it provides a measure of anxiety on a minute by minute basis, immediately related to specific stressor and we believe utilizing a simulated anxiety, provoking public speaking challenge study design provides the most appropriate and efficient path for fasedienol to potentially become the first FDA approved acute treatment of anxiety for adults with SAD.

對於這種急性適應症，我們之前與 FDA 一致認為，在臨床環境中模擬公開演講挑戰是一種適當的研究設計，並且痛苦量表或 SUDS 的主觀單位是評估 fasedienol 功效的適當主要療效終點因為它提供了每分鐘的焦慮測量，與特定的壓力源直接相關，我們相信利用模擬焦慮，激發公開演講挑戰研究設計為fasedienol 提供了最合適和有效的途徑，有可能成為第一個FDA 批准的急性藥物治療患有SAD 的成年人的焦慮症。

So to complement the positive top line results from PALISADE-2, we are currently preparing to launch two similar Phase 3 clinical trials in 2024: PALISADE-3 in the first half of 2024 and PALISADE-4 in the second half of 2024. Like the successful PALISADE-2 study, both PALISADE -3 and PALISADE-4 will be multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trials designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adult patients with SAD. after a single dose of faster data and all during a simulated anxiety provoking public speaking challenge conducted in the clinical setting, and as measured using the patient reported SUDS as the primary efficacy endpoint.

因此，為了補充 PALISADE-2 的積極頂線結果，我們目前正準備在 2024 年啟動兩項類似的 3 期臨床試驗：2024 年上半年的 PALISADE-3 和 2024 年下半年的 PALISADE-4. PALISADE- 2 研究成功後，PALISADE -3 和PALISADE-4 都將是多中心、隨機、雙盲、安慰劑對照3 期臨床試驗，旨在評估急性給藥fasedienol 緩解焦慮的有效性、安全性和耐受性成年SAD 患者的症狀。在單劑量更快的數據之後以及在臨床環境中進行的模擬引發焦慮的公開演講挑戰期間，並使用患者報告的 SUDS 作為主要療效終點進行測量。

PALISADE-3 and 4 will also have an open label extension for up to 12 months to provide additional long-term safety data. If successful, we believe either PALISADE-3 or PALISADE-4, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential fasedienol NDA submission for the acute treatment of anxiety in adults with SAD in the first half of 2026. We also plan to initiate a small fasedienol Phase 2b repeat dose study in the second half of 2024.

PALISADE-3和4還將有長達12個月的開放標籤延期，以提供額外的長期安全資料。如果成功，我們相信 PALISADE-3 或 PALISADE-4 與 PALISADE-2 一起，可以建立 fasedienol 有效性的實質證據，支持首次提交用於急性治療 SAD 成人焦慮症的潛在 fasedienol 新藥申請。2026 年下半年。我們也計劃在2024 年下半年啟動一項小型fasedienol 2b 期重複劑量研究。

The fasedienol repeat dose study will be a multi-center, randomized, double-blind, placebo-controlled clinical trial, a small one, about 60 subjects to evaluate the efficacy, safety, and tolerability of a repeat dose fasedienol that's administered 10 minutes after an initial dose to further relieve symptoms of acute anxiety in adults with SAD during the anxiety provoking public speaking challenge. That repeat dose study will consist of three different dosing arms with an open-label extension for up to 12 months.

fasedienol 重複劑量研究將是一項多中心、隨機、雙盲、安慰劑對照臨床試驗，是一項小型臨床試驗，約有60 名受試者，旨在評估10 分鐘後服用的重複劑量fasedienol 的有效性、安全性和耐受性。初始劑量可進一步緩解患有 SAD 的成年人在引發焦慮的公開演講挑戰期間的急性焦慮症狀。此重複劑量研究將包括三個不同的劑量組，並開放標籤延長長達 12 個月。

12 months open label extensions planned for the PALISADE-3, 4 and repeat dose studies are all intended to expand our fasedienol safety database. For ICH guidelines targeting 300 patients treated with fasedienol for at least six months and 100 for 12 months. To date, over 750 subjects have been exposed to fasedienol, including over 30,000 doses administered in our PALISADE open-label safety study. And we continue to be very encouraged with fasedienol safety profile in all clinical studies to date.

PALISADE-3、4 和重複劑量研究計劃的 12 個月開放標籤延期都是為了擴大我們的 fasedienol 安全資料庫。 ICH 指南針對 300 名接受 fasedienol 治療至少 6 個月的患者和 100 名患者接受 12 個月的治療。迄今為止，已有超過 750 名受試者接觸過 fasedienol，其中包括在我們的 PALISADE 開放標籤安全研究中服用的超過 30,000 劑劑量。迄今為止，我們對所有臨床研究中 fasedienol 的安全性感到非常鼓舞。

Positive PALISADE-2 data also bolster our growing confidence in the evidence supporting the potential of our entire pherine pipeline. We've had some recent advancements in a couple of other programs. Let's take a brief look at those.

PALISADE-2 的正面數據也增強了我們對支持整個 Phine 管道潛力的證據的信心。我們最近在其他幾個項目中取得了一些進展。讓我們簡單地看一下這些。

In June, we completed a successful randomized, double-blind placebo controlled Phase 1 study intended to investigate the safety and tolerability of itruvone in healthy adult subjects. That trial was conducted to stage potential Phase 2b clinical development of itruvone in the US, and it confirmed the favorable safety profile by itruvone, establishing three previous clinical trials conducted in Mexico, including a positive randomized, double-blind, placebo-controlled Phase 2a study of itruvone in major depressive disorder or MDD.

6 月，我們成功完成了一項隨機、雙盲安慰劑對照 1 期研究，旨在研究伊曲酮在健康成人受試者中的安全性和耐受性。該試驗是為了在美國進行itruvone 潛在的2b 期臨床開發，它證實了itruvone 良好的安全性，建立了先前在墨西哥進行的三項臨床試驗，其中包括一項積極的隨機、雙盲、安慰劑對照2a 期臨床試驗伊曲酮治療重度憂鬱症或 MDD 的研究。

As we advance and remain focused primarily on our PALISADE Phase 3 program for fasedienol in SAD, we also plan to explore various ways to unlock the significant potential value by itruvone as a differentiated non-systemic monotherapy for MDD through potential strategic partnering arrangements in the US as well as in major markets outside the US.

隨著我們推進並繼續主要關注用於治療SAD 的fasedienol 的PALISADE 3 期項目，我們還計劃透過在美國的潛在戰略合作安排，探索各種方法來釋放itruvone 作為MDD 的差異化非系統性單一療法的巨大潛在價值以及美國以外的主要市場。

We're also optimistic about our hormone-free non-systemic PH80 nasal spray, which has now been studied in multiple significant women's health indications. Within the last two quarters, we've announced positive results from two PH80 studies in women's health indications, the first of which was the exploratory Phase 2a study of PH80 in women diagnosed with vasomotor symptoms or hot flashes that are due to menopause.

我們也對我們的無激素非全身性 PH80 鼻噴劑感到樂觀，該噴霧劑現已在多種重要的女性健康適應症中進行了研究。在過去兩個季度中，我們宣布了兩項針對女性健康指標的PH80 研究的積極結果，其中第一項是針對被診斷患有更年期引起的血管舒縮症狀或潮熱的女性的PH80 探索性2a期研究。

And the Phase 2a study PH80 induced a significant reduction in the daily number of hot flashes compared to placebo at the end of the first week of treatment, and the improvement was maintained through each treatment week until the end of the treatment period. PH80 treatment also significantly reduced the severity of the disruption and function sweating related to hot flashes during the treatment period compared to placebo. It was well tolerated with no serious adverse events and the adverse event profiles were comparable between PH80 and placebo.

2a 期研究 PH80 在治療第一週結束時，與安慰劑相比，每日潮熱次數顯著減少，且每個治療週都保持這種改善，直到治療期結束。與安慰劑相比，PH80 治療也顯著降低了治療期間與潮熱相關的功能紊亂和出汗的嚴重程度。 PH80 的耐受性良好，沒有出現嚴重的不良事件，不良事件情況與安慰劑相當。

One of the favorable aspects of running additional trials in this particular indication is that there will be objective measures for these studies that say that it's easier to measure how many hot flashes are experienced in the frequency of those symptoms versus more subjective end points that we often see in other studies in different indications.

在這一特定適應症中進行額外試驗的有利方面之一是，這些研究將有客觀的衡量標準，這些研究表明，與我們經常使用的更主觀的終點相比，更容易測量這些症狀的頻率中經歷了多少潮熱。請參閱其他研究中的不同適應症。

The other positive PH80 data we announced recently were from an exploratory Phase 2a study of PH80 for the acute management of premenstrual dysphoric disorder or PMDD. In this study PH80 demonstrated statistically and clinically significant improvement versus placebo in symptoms of PMDD using the subject rated pen daily symptom report as early as day four continuing to day six.

我們最近宣布的其他 PH80 陽性數據來自 PH80 的一項探索性 2a 期研究，該研究用於急性管理經前煩躁症或 PMDD。在這項研究中，早在第四天一直持續到第六天，使用受試者評分筆每日症狀報告，PH80 與安慰劑相比，在統計和臨床上證明了 PMDD 症狀的顯著改善。

There are limited effective treatment options that help with both physical and mood symptoms of PMDD, and we believe these results are quite promising. Given the depth of our entire CNS pipeline and the now robust body of successful safety and efficacy studies to date, we are also pursuing multiple potential nondilutive strategic development and commercialization partnerships, both global and regional to unlock the full value of our product candidate portfolio efficiently.

有助於緩解經前憂鬱症的身體和情緒症狀的有效治療方案有限，我們相信這些結果非常有希望。鑑於我們整個中樞神經系統管道的深度以及迄今為止成功的安全性和有效性研究的穩健性，我們還在全球和區域範圍內尋求多個潛在的非稀釋性戰略開發和商業化合作夥伴關係，以有效地釋放我們的候選產品組合的全部價值。

We believe global and regional partnerships would amplify our internal expertise and development activities potentially accelerate key development time lines and enhance our overall efforts to deliver differentiated new treatment options where the current standard of care fall short.

我們相信，全球和區域合作夥伴關係將擴大我們的內部專業知識和開發活動，有可能加快關鍵開發時間線，並加強我們的整體努力，以在當前護理標準不足的情況下提供差異化的新治療方案。

As an example of this, we recently announced the receipt of $1.5 million from our exclusive negotiation agreement with Fuji Pharma regarding a potential license to develop and commercialize PH80 in hot flashes due to menopause and other indications in Japan. This is simply a right to discuss the potential for that license with us in a time-limited period. It's not a license, it's simply a nonrefundable payment to us to talk to us.

舉個例子，我們最近宣布從與富士製藥的獨家談判協議中獲得 150 萬美元，該協議涉及在日本開發和商業化用於治療更年期和其他適應症引起的潮熱的 PH80 的潛在許可。這只是在有限的時間內與我們討論該許可證的潛力的權利。這不是許可證，它只是向我們支付的不可退還的費用，用於與我們交談。

I will now turn the call over to our new CFO, Cindy Anderson, to summarize some of the highlights from our financial results for our fiscal year 2024 second quarter. Cindy has been a great recent addition to our team following the retirement of our former CFO, Jerry Dotson after his over 10 years of distinguished service to the company. Cindy?

現在，我將把電話轉給我們的新任財務長辛蒂·安德森 (Cindy Anderson)，她總結了 2024 財年第二季財務業績的一些亮點。前財務長 Jerry Dotson 為公司做出了 10 多年的傑出服務，退休後，Cindy 最近加入了我們的團隊。辛蒂？

Thank you, Shawn. It's great to be part of team. As Shawn mentioned. I'd like to highlight a few financial results for fiscal year 2024 second quarter. I also encourage everyone to review our quarterly report on Form 10-Q filed with the SEC earlier this afternoon, for additional details and disclosures.

謝謝你，肖恩。成為團隊的一員真是太好了。正如肖恩所提到的。我想重點介紹 2024 財年第二季的一些財務表現。我還鼓勵大家查看今天下午早些時候向 SEC 提交的 10-Q 表格季度報告，以了解更多詳細資訊和揭露資訊。

Research and development expenses decreased by approximately $9 million from $12 million to $3.9 million for the quarter ended September 30, 2022, and 2023, respectively. The decrease in R&D expense primarily due to the completing the initial studies of our PALISADE Phase 3 programs in SAD as well as reduced non clinical development, regulatory and outsource manufacturing activities for fasedienol and itruvone.

截至2022年9月30日及2023年9月30日的季度，研發費用分別從1,200萬美元減少約900萬美元至390萬美元。研發費用的減少主要是因為完成了 SAD 中 PALISADE 3 期專案的初步研究，以及 fasedienol 和 itruvone 的非臨床開發、監管和外包生產活動的減少。

Selling and administrative expenses decreased by approximately $0.5 million from $3.7 million for the quarter ended September 30, 2022, to $3.2 million for the quarter ended September 30, 2023, primarily due to decreased compensation, consulting fees and professional services.

銷售和管理費用從截至2022年9月30日的季度的370萬美元減少約50萬美元，至截至2023年9月30日的季度的320萬美元，主要是由於薪酬、諮詢費和專業服務的減少。

Our net loss attributed to common stockholders for the quarter ended September 30, 2023 was approximately $6.6 million versus a net loss of approximately $17.5 million for the quarter ended September 30, 2022. At September 30, 2023, Vistagen had cash and cash equivalents of approximately $37.6 million. From September 30, we received approximately $93.5 million in net proceeds from an underwritten equity financing and $1.5 million from Fuji Pharma under exclusive negotiation agreements.

截至2023 年9 月30 日的季度，我們歸屬於普通股股東的淨虧損約為660 萬美元，而截至2022 年9 月30 日的季度，我們的淨虧損約為1,750 萬美元。截至2023 年9月30 日，Vistagen 的現金和現金等價物約為3,760 萬美元。自 9 月 30 日起，我們從承銷股權融資中獲得了約 9,350 萬美元的淨收益，並根據獨家談判協議從富士製藥獲得了 150 萬美元。

If our PALISADE Phase 3 program is successful, We believe that our current cash position will be sufficient to fund our operations through potential submission of a US new drug application for fasedienol for the acute treatment of anxiety in adults with SAD. As a reminder, please refer to our quarterly report on Form 10-Q filed today with the SEC for additional details and disclosures. I will now turn the call back over to Shawn.

如果我們的 PALISADE 3 期計劃取得成功，我們相信我們目前的現金狀況將足以通過可能提交美國新藥 fasedienol 申請來資助我們的運營，該申請用於急性治療 SAD 成人的焦慮症。謹此提醒，請參閱我們今天向 SEC 提交的 10-Q 表格季度報告，以了解更多詳細資訊和揭露資訊。我現在將把電話轉回給肖恩。

Thank you, Cindy. So to wrap up, our dedication to enhancing global mental health and the overall well-being of individuals who are affected by a wide range of CNS disorders is unwavering. And as we are progressing through the next phases of our corporate development strategy, we're doing that with confidence in the potential of our PALISADE Phase 3 program for fasedienol in social anxiety disorder as well as the clinical stage assets that are up and down our entire pipeline.

謝謝你，辛蒂。總而言之，我們堅定不移地致力於增強全球心理健康和受各種中樞神經系統疾病影響的個人的整體福祉。隨著我們公司發展策略下一階段的進展，我們對 PALISADE 3 期 fasedienol 治療社交焦慮症計畫的潛力以及我們上下的臨床階段資產充滿信心。整個管道。

We've got a capable team, got a robust pipeline, and we've got a steadfast commitment to pioneer and differentiated solutions, totally different approaches to the current standard of care for multiple sizable CNS markets that have substantial unmet needs.

我們擁有一支有能力的團隊，擁有強大的產品線，並且堅定地致力於開拓和差異化的解決方案，為多個具有大量未滿足需求的大型中樞神經系統市場的當前護理標準提供完全不同的方法。

So on behalf of our entire Vistagen team, once again, we're grateful for the privilege and for the opportunity to create meaningful impacts for patients, not only in the US, but all around the world, who are impacted in their daily lives by these disruptive and often disabling serious CNS conditions.

因此，我代表我們整個 Vistagen 團隊，再次感謝您有幸為患者創造有意義的影響，不僅是在美國，而且是在世界各地，他們的日常生活受到了以下因素的影響：這些具有破壞性且經常致殘的嚴重中樞神經系統疾病。

Thank you, Shawn. Operator, we'd like to open up the call for questions from the sell-side analysts participating on the call today.

謝謝你，肖恩。營運商，我們想開始向參加今天電話會議的賣方分析師提問。

Yes, sir. (Operator Instructions) Andrew Tsai, Jefferies.

是的先生。 （操作員說明）Andrew Tsai，Jefferies。

Hey, good afternoon. I appreciate taking the questions and congrats on the progress. Great to see you making strides here. So obviously, the next step for -- PH94B is to start the PALISADE-3 in first half of 2024. So what needs to be done for you to start earlier in Q1 rather than Q2? What exactly are the bottlenecks there next? Thanks.

嘿，下午好。我很高興接受這些問題並祝賀取得的進展。很高興看到你在這裡取得進步。顯然，PH94B 的下一步是在 2024 年上半年啟動 PALISADE-3。那麼，需要做什麼才能在第一季而不是第二季更早啟動？接下來的瓶頸到底是什麼？謝謝。

Thanks, Andrew. Appreciate the question. I agree, thanks to INN, it is easy to say PH94B than fasedienol. We hope the world will get used to that soon enough. The answer is we are targeting Q1, and so we are -- everything we're doing right now is in preparation to launch PALISADE-3 in the first quarter of 2024. So all the pregame work, a lot of that's already been underway for several months now. And of course, we bring a lot of knowledge from the prior studies to bear into that effort. So and that's our target and we'd expect to be able to have PALISADE-4 follow hopefully early in the second quarter -- early in the second half of '24.

謝謝，安德魯。感謝這個問題。我同意，感謝 INN，很容易說 PH94B 比 fasedienol。我們希望世界能夠盡快習慣這一點。答案是我們的目標是第一季度，所以我們現在所做的一切都是為了在 2024 年第一季度推出 PALISADE-3 做準備。因此，所有賽前工作，其中很多工作已經在進行中現在幾個月了。當然，我們從先前的研究中汲取了大量的知識，並將其運用到這項工作中。這就是我們的目標，我們希望能夠在第二季初（即 24 年下半年初）推出 PALISADE-4。

Okay. Very good. Can you summarize for us just one more time all the things you're going to do differently and PALISADEs 3 and 4 to ensure study execution, what removal/deletions or additions are you making to these studies relative to the prior two studies?

好的。非常好。您能否再為我們總結一下您將採取的所有不同措施以及 PALISADE 3 和 4 以確保研究執行，相對於前兩項研究，您對這些研究進行了哪些刪除/刪除或添加？

Yeah, great. Thank you for that question. It's important question. As you obviously know, the macro world is fundamentally different as we move into the first part of '24 as it is right now relative to '22 or '21, certainly '21. And what's nice to see is the return to normal of a lot of the typical conventions that are associated with efficient execution, preparation and execution of clinical studies.

很好。謝謝你提出這個問題。這是一個重要的問題。正如您顯然知道的那樣，當我們進入“24”的第一部分時，宏觀世界已經發生了根本的不同，因為它現在相對於“22”或“21”，當然是“21”。令人高興的是許多與臨床研究的有效執行、準備和執行相關的典型慣例恢復正常。

As it relates to our particular protocol and the studies that we'll be initiating going forward with this public speaking challenge in the study design that's associated with SUDS, there are certain things that may or may not have been in effect, but we know that it's possible for COVID to disrupt the olfactory system a bit. So there will be no subjects enrolled that have had a nasal swab within a month for RSV, for COVID, for flu. They'll have to pass the smell test, an olfactory -- clinical factory test in order to be eligible to be no high-frequency vapors or smokers or drinkers -- drinkers of Red Bull and things of that nature. There's a high level of scrutiny that's associated with the front end with assessing patient eligibility,

由於它涉及我們的特定方案以及我們將在與 SUDS 相關的研究設計中進行公開演講挑戰的研究，因此某些事情可能有效，也可能無效，但我們知道新冠病毒可能會稍微擾亂嗅覺系統。因此，登記的受試者不會在一個月內接受過鼻拭子檢測 RSV、COVID 或流感。他們必須通過氣味測試，即嗅覺臨床工廠測試，才有資格成為不吸高頻蒸汽、不吸煙或不喝酒的人，不喝紅牛和類似性質的東西的人。與評估患者資格的前端相關的高水準審查，

Josh Prince is on. Josh is our COO, and oversees our team. Josh, you want to highlight a few other things?

喬許·普林斯上場了。喬許是我們的營運官，負責監督我們的團隊。喬希，您想強調其他一些事情嗎？

Yeah, I think you captured a couple there, Shawn. And it's important to think of -- essentially we're doing everything we can to ensure that we have the patience for this one-dose public speaking challenge, make sure you have patients in there that can get the benefit from product. It's those things that Shawn mentioned that's also kind of do the oversight in terms of sites in terms of changing the way that we monitor and work with our CRO over the sites to make sure that we're on top of things that we have data reviews, eligibility reviews, those types of things.

是的，我想你在那裡拍到了一對情侶，肖恩。重要的是要考慮到——本質上我們正在盡一切努力確保我們有耐心應對這項單劑公開演講挑戰，確保那裡的患者可以從產品中受益。 Shawn 提到的這些事情也可以對網站進行監督，改變我們在網站上監控和與 CRO 合作的方式，以確保我們掌握數據審核的情況，資格審查，諸如此類的事情。

So those are the key is to make sure that we have a successful study. It's really all about the execution of that public speaking challenge with the right patients in there, and that's where we're focused forward.

所以這些都是確保我們研究成功的關鍵。這實際上是關於與合適的患者一起執行公開演講挑戰，這就是我們關注的重點。

Some of the other things, Andrew, that are possible. Obviously, the surveillance is -- it's fundamentally changed since even PALISADE-2. So part of our operating model is to make sure we have our own people on sites in addition to the resources that are brought to bear by CROs in the sites themselves. Of course, no masks will be involved in PALISADE-3 or PALISADE-4, which is a big difference from the prior studies.

安德魯，其他一些事情是可能的。顯然，自 PALISADE-2 以來，監視已經發生了根本性的變化。因此，我們營運模式的一部分是確保除了 CRO 在網站本身提供的資源之外，我們還有自己的人員在網站上。當然，PALISADE-3或PALISADE-4中不會涉及掩模，這與先前的研究有很大不同。

So just trying to get back to a situation where the macro environment allows us to apply a lot of the trade craft that's been historically successful when we're trying to not only plan for, let's say, with an in-person investigators' meeting, the likes of which weren't possible with some of the earlier studies. That starts things off and then the ability to interact more frequently with sites in person, all that's important when you're trying to generate rigorous adherence to the study protocol.

因此，只是試圖回到這樣一種情況：宏觀環境允許我們應用許多歷史上成功的貿易技巧，當我們試圖不僅計劃，比方說，透過面對面的調查員會議，早期的一些研究不可能做到這一點。這是一切的開始，然後是更頻繁地親自與網站互動的能力，當您試圖嚴格遵守研究方案時，所有這些都很重要。

I think also what we'll see is better predictability about site staff in general. The depth of the set, the staff's, the more consistent execution -- ability to execute between studies, study visits, I should say, or predictably planned them. So a lot of things that are essential to be able to execute a protocol such as we've got in place for the successful PAL-2 study. And as we bring that into PAL-3 and 4, even more confidence in the overall environment than was the case in '22.

我認為我們還將看到現場工作人員總體上具有更好的可預測性。佈景的深度、工作人員的執行力、更一致的執行力——我應該說，在研究、研究訪問或可預見的計劃之間執行的能力。因此，為了能夠執行協議，很多事情都是必不可少的，例如我們為成功的 PAL-2 研究所做的準備。當我們將其引入 PAL-3 和 4 時，我們對整體環境的信心甚至比 22 年的情況更有信心。

Thank you. And maybe last one for me. I want to be respectful of the other colleagues here. Can you give us a flavor of what additional data will be presented at your medical conferences tomorrow for those that are not diagnosed? And I think there's another asset that's where there's data being presented. So what would be the key takeaways that we should take home for these presentations? Thank you.

謝謝。也許對我來說是最後一個。我想尊重這裡的其他同事。您能為我們介紹明天的醫學會議將為那些未確診的患者提供哪些額外數據嗎？我認為還有另一種資產就是呈現數據的地方。那麼，我們應該從這些演示中獲得哪些關鍵要點呢？謝謝。

Thanks. Well, a key effort right now is to obviously raise awareness of what the clinical audience hasn't seen in many, many years in this indication. So to be able -- you'll see mostly from those presentations on the top line results from PALISADE-2 as well, some data from our open-label study, which is remarkable. Given the number of doses and the number of subjects exposed to the drug in an anxiety disorder, you still see it and then some data from our PH80 study.

謝謝。嗯，現在的一個關鍵工作是明顯提高臨床觀眾對這個適應症很多年沒有見過的認識。因此，您將主要從 PALISADE-2 的頂線結果的這些演示中看到，以及來自我們的開放標籤研究的一些數據，這是非常了不起的。考慮到焦慮症患者的劑量數量和接觸該藥物的受試者數量，您仍然會看到它以及我們 PH80 研究中的一些數據。

So key to what we are doing now obviously is to raise awareness of what's been achieved as well as to raise awareness of what's ahead, not only in the markets, but also within the clinical communities that we know ultimately will be key pieces of the puzzle downstream.

因此，我們現在所做的關鍵顯然是提高人們對已取得的成就的認識，以及提高對未來的認識，不僅在市場上，而且在我們知道最終將成為難題的關鍵部分的臨床社區內下游。

Great. Thank you very much.

偉大的。非常感謝。

Thanks, Andrew.

謝謝，安德魯。

Tim Lugo, William Blair.

提姆·盧戈，威廉·布萊爾。

Thanks for taking the question. Can you update us on the lack of abuse potential for fasedienol? I think I got that right. I know you have some preclinical data around that, but I'm wondering if there's anything incremental coming out of PAL-2 and just maybe your interactions with the agency as well?

感謝您提出問題。您能否向我們介紹有關 fasedienol 缺乏濫用可能性的最新情況？我想我是對的。我知道你們有一些關於這方面的臨床前數據，但我想知道 PAL-2 是否有任何增量，也許你們與該機構的互動也有？

Yeah. Thanks, Tim. Good to hear from you. Obviously the data that we teed up to the agency back in '22 was focused on whether or not there were signals and had been any signals at that time of abuse liability potential, given that this is a nasal spray and a lot of folks were wondering, well, what happens when you put something in the nose is it become addictive?

是的。謝謝，蒂姆。很高興聽到你的消息。顯然，我們在 22 年向該機構提供的數據重點是是否存在濫用可能性的信號以及當時是否存在任何信號，因為這是一種鼻噴霧劑，很多人都想知道好吧，當你把東西放進鼻子裡會發生什麼，它會讓人上癮嗎？

And the uniqueness of this mechanism of action that we have with fasedienol and the rest of the variants is important to note because what we're dealing with and we've done multiple studies not only on the clinical side, but some important preclinical ones associated with the reality that there's no potentiation of GABA, for example, as you see with benzodiazepines. Radio labeling the drug showed no systemic exposure.

我們對 fasedienol 和其他變異的這種作用機制的獨特性值得注意，因為我們正在處理的問題以及我們不僅在臨床方面進行了多項研究，而且還進行了一些與相關的重要臨床前研究事實上，GABA 並沒有增強作用，就像你在苯二氮平類藥物中看到的那樣。該藥物的放射性標記顯示沒有全身暴露。

So the drugs, these variants don't have to get into the brain and act directly on CNS neurons in the brain, including the abuse liability receptors that are typically out there. So we put a whole body of work to the agency at the time and asked the question what came back from as we reported was they didn't see any reason for us to have to do a human abuse liability study at that time.

因此，這些藥物、這些變異體不必進入大腦並直接作用於大腦中的中樞神經系統神經元，包括通常存在的濫用傾向受體。因此，我們當時向該機構投入了全部工作，並提出了一個問題，正如我們報道的那樣，他們認為我們當時沒有任何理由必須進行人類虐待責任研究。

Since then, what's been delivered is all of the data from the open-label study, which had 481 subjects, and the adverse event profile in that study was remarkable, especially again for drug and neuropsychiatry where the most common adverse effect was our adverse event was headache, and that was reported and really only 17% overall, but 8.7% were drug-related and beyond COVID-19, which was 0% drug-related, there was no other treatment emergent adverse effect in more than 5% of the participants.

從那時起，所提供的是開放標籤研究的所有數據，該研究有481 名受試者，該研究中的不良事件概況非常引人注目，特別是對於藥物和神經精神病學，其中最常見的不良反應是我們的不良事件是頭痛，據報道，總體上只有17%，但8.7% 與藥物相關，除了COVID-19（0% 與藥物相關）之外，超過5% 的患者沒有其他治療出現的不良反應參與者。

And in the PALISADE-2 study, similar in PALISADE-1, similar safety profile, although even less prevalent in terms of the treatment emergent adverse effects. So these are events. These data overall, nonclinical and clinical really continue to reinforce our belief in why we don't see these safety concerns you typically see associated with benzones or antidepressants. These are not systemically absorbed drugs. You cannot detect them in the plasma.

在 PALISADE-2 研究中，與 PALISADE-1 相似，安全性相似，儘管就治療中出現的不良反應而言甚至不太常見。所以這些都是事件。總體而言，這些非臨床和臨床數據確實繼續強化了我們的信念，為什麼我們沒有看到您通常看到的與苯酮或抗憂鬱藥物相關的安全問題。這些不是全身吸收的藥物。你無法在等離子體中檢測到它們。

And so you're basically using the nose as a portal to achieve the effects from different regions of the brain that are associated with these different indications, not having to go in the mouth and might be metabolized by the liver, bump into other drugs through the bloodstream, other blood-brain barrier into the brain, all those are major factors that really distinguish this class from everything that's historically been approved or is even in development for these neuropsychiatric indications.

因此，您基本上使用鼻子作為門戶來實現與這些不同適應症相關的大腦不同區域的效果，而不必進入口腔並可能被肝臟代謝，通過碰撞到其他藥物血液、進入大腦的其他血腦屏障，所有這些都是真正將此類藥物與歷史上已批准的或甚至正在開發的用於這些神經精神適應症的所有藥物區分開來的主要因素。

So it's not a concern we've had in the past, it's not a concern the FDA had when we showed them the data, and it's certainly not a concern that we have now after and tens of thousands of more doses and hundreds of more subjects since we first got that read from the FDA.

因此，這不是我們過去所擔心的問題，也不是我們向 FDA 展示數據時所擔心的問題，當然也不是我們現在在數以萬計的劑量和數百名受試者之後所擔心的問題。自從我們第一次從FDA 得到這項消息以來。

That's great to hear. Thank you.

聽到這個消息我很高興。謝謝。

We have no further questions in the queue at this time. I would now like to turn the call back over to today's speakers for any additional or closing remarks.

目前我們隊列中沒有其他問題。現在我想將電話轉回給今天的講者，請其補充或結束發言。

Thank you, operator. If there are any additional questions that you might have, please don't hesitate to contact us here, Vistagen at ir@vistagen.com or contact me those listed on our press release issued earlier today as we noted or on the contact section of our website. We also encourage you to register for email updates on our website to stay connected with the latest news from Vistagen.

謝謝你，接線生。如果您還有任何其他問題，請隨時透過 ir@visagen.com 聯絡我們 Vistagen，或透過今天早些時候發布的新聞稿或我們的聯絡方式部分中列出的資訊與我聯絡。網站。我們也鼓勵您在我們的網站上註冊電子郵件更新，以便隨時了解 Vistagen 的最新消息。

Again, thank you for participating on the call today. We appreciate everyone's attention and continued support and look forward to keeping you current on our continued progress. This concludes the call. Have a tremendous day.

再次感謝您參加今天的電話會議。我們感謝大家的關注和持續支持，並期待您隨時了解我們的持續進展。通話就此結束。祝你有美好的一天。

This does conclude today's program. Thank you for your participation. You may disconnect at any time.

今天的節目到此結束。感謝您的參與。您可以隨時斷開連線。