Vistagen Therapeutics Inc (VTGN) 2025 Q1 法說會逐字稿

Ladies and gentlemen, greetings and welcome to Vistagen Therapeutics fiscal year 2025 first-quarter corporate update conference call. At this time, all participants are in a listen-only mode. (Operator Instructions) As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mark McPartland, SVP, Investor Relations at Vistagen. Please go ahead.

女士們、先生們，大家好，歡迎參加 Vistagen Therapeutics 2025 財年第一季公司最新狀況電話會議。此時，所有參與者都處於只聽模式。（操作員指示）謹此提醒，本次會議正在錄製中。現在我很高興向您介紹主持人 Mark McPartland，Vistagen 投資者關係資深副總裁。請繼續。

Thank you, Ryan, and good afternoon, everyone, and welcome to Vistagen's fiscal year 2025 first-quarter corporate update conference call and webcast. This afternoon, we filed our quarterly report with the Securities Exchange Commission on SEC Form 10-Q for a quarter ended June 30, 2024, and issued a press release providing an overview of our continued progress. We encourage you to review the release and our 10-Q, which can be found in the investor section of our website. We will make forward-looking statements regarding our business during today's call based on current expectations and information.

謝謝 Ryan，大家下午好，歡迎參加 Vistagen 2025 財年第一季公司更新電話會議和網路廣播。今天下午，我們向美國證券交易委員會提交了截至 2024 年 6 月 30 日的季度 SEC 10-Q 季度報告，並發布了一份新聞稿，概述了我們的持續進展。我們鼓勵您查看新聞稿和我們的 10-Q，您可以在我們網站的投資者部分找到這些內容。在今天的電話會議中，我們將根據當前的預期和資訊就我們的業務做出前瞻性聲明。

These forward-looking statements speak only as of today, except as required by law. We do not assume any duty to update any forward-looking statements made today or in the future. 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 risk and factors that could affect our business and financial results is included in our fiscal year 2025 first quarter 10-Q for the period ended June 30, 2024 and will be made in the future filings that we make with the SEC from time-to-time, all of which will be available in the Investor section of our website and of course on the SEC's website.

除法律要求外，這些前瞻性陳述僅代表今天的情況。我們不承擔更新今天或將來做出的任何前瞻性陳述的責任。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。有關可能影響我們業務和財務業績的風險和因素的更多資​​訊包含在截至 2024 年 6 月 30 日的 2025 財年第一季度 10-Q 中，並將在我們今後向 SEC 提交的文件中提供-隨時，所有這些都將在我們網站的投資者部分以及美國證券交易委員會的網站上提供。

With the formalities completed, we warmly welcome our stockholders, sell-side analysts, and others interested in Vistagen. I'm joined on our call today by Shawn Singh, our Chief Executive Officer; Cindy Anderson, our Chief Financial Officer; and Josh Prince, our Chief Operating Officer. Shawn will provide an update on the lead programs in our novel class of neurocircuitry-focused pherine drug candidates and our clinical stage pipeline. After that, the conclusion of our prepared remarks, there will be a brief opportunity for questions from the sell-side analysts participating on the call.

手續完成後，我們熱烈歡迎我們的股東、賣方分析師和其他對 Vistagen 感興趣的人。我們的執行長肖恩辛格 (Shawn Singh) 也參加了今天的電話會議。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)。肖恩（Shawn）將提供我們以神經迴路為重點的新型菲林候選藥物和我們的臨床階段管道的主要項目的最新資訊。之後，我們準備好的發言結束後，參加電話會議的賣方分析師將有一個簡短的提問機會。

As a reminder, this call is being webcast and will be available for replay after completion. The replay link can also be found in the investor section of our website. I will now turn the call over to our Chief Executive Officer, Shawn Singh.

謹此提醒，本次電話會議正在進行網路直播，結束後可重播。重播連結也可以在我們網站的投資者部分找到。我現在將把電話轉給我們的執行長肖恩辛格。

Thank you, Mark, and good afternoon everyone. Thank you for joining our call today. For those of you who are joining us for the first time, we are a neuroscience company with a diverse pipeline that includes multiple clinical stage product candidates in Phase 2 and Phase 3 development. Each of these is a novel, non-systemic, neurocircuitry-focused product candidate.

謝謝你，馬克，大家下午好。感謝您今天加入我們的電話會議。對於第一次加入我們的人來說，我們是一家神經科學公司，擁有多元化的產品線，其中包括處於 2 期和 3 期開發的多個臨床階段候選產品。其中每一個都是新穎的、非系統性的、以神經迴路為重點的候選產品。

Our three lead clinical development programs target large markets with stale standards of care that leave millions of individuals with unsatisfied medical needs, specifically individuals affected by their profound fear and anxiety associated with social anxiety disorder, the serious and potentially life-threatening impacts of depression, and the disruptive effects of menopausal hot flashes. For decades, the standard-of-care in these very large indications, has been anchored in oral medications that require systemic uptake and are associated with a bundle of worrisome side effects and safety concerns, prolonged onset of action, and limited efficacy. And our mission is to change that, to change that with our pioneering neuroscience and our new class of clinical stage product candidates called pherine.

我們的三個主要臨床開發項目針對的是護理標準陳舊的大型市場，這些市場導致數百萬人的醫療需求未得到滿足，特別是受到與社交焦慮症相關的深刻恐懼和焦慮、抑鬱症的嚴重且可能危及生命的影響的個人，以及更年期潮熱的破壞性影響。幾十年來，這些非常大的適應症的護理標準一直以口服藥物為主，這些藥物需要全身吸收，並與一系列令人擔憂的副作用和安全問題、起效時間長和療效有限有關。我們的使命是改變這一現狀，透過我們開創性的神經科學和名為 pherine 的新型臨床階段候選產品來改變這一現狀。

Distinguished from all systemic oral medications approved by the FDA, our lead neuroactive pherine, Fasedienol for social anxiety, Itruvone for depression, and PH80 for menopausal hot flashes are intentionally formulated as nasal sprays to rapidly activate unique nose-to-brain neural circuits to achieve therapeutic effects without requiring systemic uptake or direct action on neurons in the brain and to do so with favorably differentiated safety profiles that we've observed in all clinical studies of our pherine product candidates that have been completed to-date. Pherine use the nose and key neurons located in the olfactory epithelium, as a portal to activate neurocircuitry in different regions of the brain that impact multiple medical conditions. And again, they do that without having to travel through the whole body or even into the brain.

與FDA 核准的所有全身性口服藥物不同，我們的主要神經活性藥物pherine、用於治療社交焦慮的Fasedienol、用於治療憂鬱症的Itruvone 和用於治療更年期潮熱的PH80 被特意配製為鼻噴劑，以快速激活獨特的鼻到腦神經迴路，以實現無需全身攝取或直接作用於大腦中的神經元即可產生治療效果，並且具有我們在迄今為止已完成的菲林產品候選者的所有臨床研究中觀察到的有利差異化的安全性。菲林利用鼻子和位於嗅覺上皮的關鍵神經元作為門戶，激活大腦不同區域的神經迴路，從而影響多種醫療狀況。再說一次，他們不需要穿過整個身體，甚至不需要進入大腦就可以做到這一點。

Those fundamental differences have enabled us to achieve historic clinical success in a Phase 3 trial for the acute treatment of Social Anxiety Disorder, or SAD, that we reported last year, as well as also see positive results in exploratory Phase 2 trials involving patients with major depressive disorder, menopausal hot flashes, premenstrual dysphoric disorder, and psychomotor impairment due to mental fatigue. Our top priority, the lead neuroscience program in which the vast majority of our team and our capital are focused on, is our US registration-directed Palisade Phase 3 program for Fasedienol. That is our investigational fairy nasal spray for the acute treatment of SAD. There's no FDA-approved medication for the acute treatment of SAD, which is a very large, growing, and underserved market that affects 12% of adults in the US.

這些根本差異使我們能夠在去年報告的急性治療社交焦慮症（SAD）的3 期臨床試驗中取得歷史性的臨床成功，並且在涉及患有嚴重社交焦慮障礙的患者的探索性2 期試驗中也看到了正面的結果。我們的首要任務，即我們團隊和資本的絕大多數人都關注的領先神經科學項目，是我們在美國註冊的 Palisade 3 期 Fasedienol 項目。這是我們用於急性治療 SAD 的研究性仙女鼻噴劑。目前尚無 FDA 批准的用於 SAD 急性治療的藥物，這是一個非常龐大、不斷增長且服務不足的市場，影響著美國 12% 的成年人。

As I noted many times, our principal goal is to change that. Last year with our PALISADE-2 Phase 3 trial of Fasedienol, we reported the first ever positive Phase 3 trial of a drug candidate for the acute treatment of SAD. Earlier this year we launched another Phase III trial, PALISADE-3, designed similarly to PALISADE-2 with the objective of replicating the success of that study. The enrollment in the PALISADE-3 study is on track and we're also on track to initiate our PALISADE-4 Phase 3 study in the second half of this year, as we've previously guided.

正如我多次指出的，我們的主要目標是改變這種狀況。去年，透過 Fasedienol 的 PALISADE-2 3 期試驗，我們報告了首個用於急性治療 SAD 候選藥物的 3 期試驗結果。今年早些時候，我們啟動了另一項 III 期試驗 PALISADE-3，其設計與 PALISADE-2 類似，目的是複製研究的成功。PALISADE-3 研究的入組工作正在按計劃進行，我們也將按照我們先前的指導，在今年下半年啟動 PALISADE-4 第 3 期研究。

That study will have the same design as PALISADE-3 and the same objective of replicating the positive results from PALISADE-2. Both of these Phase 3 studies as well as an exploratory Phase 2A repeat dose study will read out next year. We believe either PALISADE-3 or PALISADE-4, if successful, and together with PALISADE-2, may establish the substantial evidence of the effectiveness of fasedienol in support of a potential US new drug application, submission to the FDA, which if approved, could establish fasedienol as the first ever FDA-approved acute treatment of SAD. A new treatment option with the potential to be used on demand as needed by millions of Americans whose serious and sometimes life-threatening anxiety and fear of embarrassment, judgment, humiliation in a wide range of social and performance situations affect their daily lives over many years and potentially and unfortunately sometimes lead to depression and even suicide.

該研究將採用與 PALISADE-3 相同的設計，並具有複製 PALISADE-2 的積極結果的相同目標。這兩項 3 期研究以及探索性 2A 期重複劑量研究將於明年發表。我們相信，PALISADE-3 或 PALISADE-4 如果成功，並與 PALISADE-2 一起，可以建立 fasedienol 有效性的實質證據，以支持潛在的美國新藥申請，提交給 FDA，如果獲得批准，可以將fasedienol 確立為FDA 核准的首個SAD 急性治療藥物。一種新的治療選擇，有可能根據數百萬美國人的需要按需使用，這些美國人多年來在各種社交和表演場合中嚴重地、有時危及生命的焦慮和對尷尬、評判、羞辱的恐懼影響著他們的日常生活不幸的是，有時會導致憂鬱甚至自殺。

So again, our US registration-directed PALISADE Phase 3 program for fasedienol for the acute treatment of SAD is our top priority, and we are on track and well-funded to do what's necessary to put us in a position with the potential to achieve that important and very valuable goal for patients and for our stockholders. We’re also staging our other two lead pherine clinical-stage programs in depression and hot flashes for further Phase 2 development in the US, building on positive results in exploratory Phase 2a studies in each of these large market indications, each of which has stale standards of care and non-systemic pharmacological treatment alternative. And what we've seen in Phase II from non-systemic itruvone for MDD and non-systemic hormone-free PH80 for menopausal hot flashes so far as to both efficacy and safety is driving our confidence in the potential of these product candidates to improve lives. Itruvone holds the potential to emerge as a novel and fundamentally distinct stand-alone treatment for major depressive disorder.

再說一次，我們在美國註冊的PALISADE 3 期計畫是用於急性治療SAD 的fasedienol ，這是我們的首要任務，我們正在走上正軌，並且資金充足，可以採取必要的行動，使我們有可能實現這一目標對病人和我們的股東來說，這是一個重要且非常有價值的目標。我們也在美國開展另外兩個針對憂鬱症和熱潮紅的領先 pherine 臨床階段項目，以在每個大型市場適應症的探索性 2a 期研究的積極成果的基礎上進行進一步的 2 期開發。護理標準和非全身性藥物治療替代方案。我們在 II 期中看到的非全身性伊特魯酮治療 MDD 和非全身性不含激素 PH80 治療更年期潮熱的療效和安全性，使我們對這些候選產品改善生活的潛力充滿信心。Itruvone 有潛力成為一種新穎且本質上獨特的重度憂鬱症獨立治療方法。

And we're preparing and strategizing for a Phase 2b development of itruvone in the US, as a product candidate with the potential to help individuals who suffer from depression gain relief from their MDD symptoms swiftly and without many side effects of currently available systemic treatment options. Itruvone is distinguished by its favorable safety profile that's been observed in studies that have been completed to-date, which is not associated with unwanted sexual side effects, for example, or weight gain potential for abuse. And finally, our non-systemic hormone-free pherine product or product candidate for menopausal hot flashes, PH80 holds considerable medical commercial promise in multiple women's health conditions, but most notably menopausal high flashes that affect millions of women around the world. Similar to what we have accomplished to enable further Phase 2 development of itruvone for MDD in the US, our ongoing nonclinical program for PH80 aims to enable our US IND to further Phase 2 clinical development of PH80 in the US, as well and to do that for menopausal hot flashes.

我們正在為 itruvone 在美國的 2b 期開發做準備和製定策略，作為一種候選產品，有可能幫助憂鬱症患者迅速緩解 MDD 症狀，並且不會產生目前可用的全身性治療方案的許多副作用。伊特魯酮的特點是其良好的安全性，迄今為止已完成的研究已觀察到該安全性，與不良的性副作用（例如，濫用的體重增加可能性）無關。最後，我們的非全身性無激素菲林產品或治療更年期潮熱的候選產品PH80 在多種女性健康狀況中具有相當大的醫療商業前景，但最引人注目的是影響全球數百萬女性的更年期潮熱。與我們為在美國進一步開展伊特魯酮治療MDD 的2 期開發所取得的成就類似，我們正在進行的PH80 非臨床計劃旨在使我們的美國IND 能夠在美國進一步開展PH80 的2 期臨床開發，並做到這一點用於更年期潮熱。

We are confident that millions of women who are affected by menopausal hot flashes would prefer a novel non-systemic hormone-free treatment option over the current therapies. With that, I'll turn the call over to Cindy, our CFO to summarize some of the financial highlights from the last quarter. Cindy?

我們相信，與現有療法相比，數百萬受更年期潮熱影響的女性會更喜歡新型非全身性無荷爾蒙治療方案。接下來，我將把電話轉給我們的財務長辛迪，總結上一季的一些財務亮點。辛蒂？

Thank you, Shawn. As Shawn mentioned, I will highlight a few financial results from our fiscal year 2025 first quarter. I also encourage everyone to review our report on Form 10-Q filed with the SEC earlier this afternoon for additional details and disclosures. Research and development expenses were $7.6 million for the quarter ending June 30, 2024, compared to $4.2 million for the same period last year.

謝謝你，肖恩。正如 Shawn 所提到的，我將重點介紹 2025 財年第一季的一些財務表現。我還鼓勵大家查看我們今天下午早些時候向 SEC 提交的 10-Q 表報告，以了解更多細節和披露資訊。截至 2024 年 6 月 30 日的季度，研發費用為 760 萬美元，去年同期為 420 萬美元。

The increase in R&D expenses was primarily due to an increase in clinical and development expenses related to the commencement of PALISADE-3 and costs related to preparation for the initiation of PALISADE-4 Phase 3 trial of fasedienol in SAD, an increase in headcount costs and increase in consulting and professional fees. General and administrative expenses was $4.6 million for the quarter ending June 30, 2024, compared to $3 million for the same period last year. The increase in G&A expenses was primarily due to an increase in headcount costs and professional service expenses to support the continued expansion of our administrative activities. Our net loss attributable to common shareholders was $10.7 million for the quarter ended June 30, 2024 compared to $6.9 million for the same period last year.

研發費用的增加主要是由於與 PALISADE-3 的啟動相關的臨床和開發費用的增加以及與準備啟動 PALISADE-4 fasedienol 在 SAD 中的 3 期試驗相關的費用的增加、人員成本的增加以及諮詢和專業費用增加。截至 2024 年 6 月 30 日的季度，一般及管理費用為 460 萬美元，去年同期為 300 萬美元。一般及行政費用的增加主要是由於員工成本和專業服務費用的增加，以支持我們行政活動的持續擴張。截至 2024 年 6 月 30 日的季度，我們歸屬於普通股股東的淨虧損為 1,070 萬美元，而去年同期為 690 萬美元。

As of June 30, 2024, we had cash, cash equivalents and marketable securities of $108.4 million. 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.

截至 2024 年 6 月 30 日，我們擁有現金、現金等價物及有價證券為 1.084 億美元。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。

Thanks, Cindy. What drives our team day in and day out is the opportunity to improve patient lives with our pioneering neuroscience, along with the potential value for stockholders that often accompanies that type of accomplishment. With our on-track progress in our US registration-directed PALISADE Phase 3 program for fasedienol that's aimed at the acute treatment of SAD, which is a mental health disorder that's growing in prevalence. It's now affecting over 30 million Americans on the other side of the pandemic, and none of them have yet an FDA approved, flexible, patient-tailored acute treatment option. So we are confident in advancing on our goal to secure that first FDA approval.

謝謝，辛蒂。日復一日地推動我們團隊前進的動力是利用我們開創性的神經科學改善患者生活的機會，以及通常伴隨這種成就而來的股東的潛在價值。隨著我們在美國註冊的 PALISADE 3 期 fasedienol 計畫取得進展，該計畫旨在急性治療 SAD，這是一種流行率不斷上升的精神健康疾病。目前，它正在影響超過 3000 萬處於大流行另一邊的美國人，而他們中沒有一個人還沒有 FDA 批准的、靈活的、針對患者的急性治療選擇。因此，我們有信心推進我們的目標，獲得 FDA 的首次批准。

And it's a very serious and very life-threatening and highly prevalent indication that requires the kind of serious attention and effort that our team is putting on driving this PALISADE Phase 3 program forward, building on the success we've achieved last year from the PALISADE-2 study. So on behalf of everybody at Vistagen, I just want to thank you all for your continued interest and your continued support on our mission.

這是一個非常嚴重、非常危及生命且非常普遍的跡象，需要我們的團隊在去年 PALISADE 取得的成功的基礎上，給予認真的關注和努力，推動 PALISADE 第三階段計劃向前發展。因此，我謹代表 Vistagen 的所有人，感謝大家對我們使命的持續關注和持續支持。

Thank you, Shawn. Operator, we would now like to open the call for questions from the sell-side analysts participating today.

謝謝你，肖恩。營運商，我們現在要開始向今天參與的賣方分析師提問。

(Operator Instructions) Paul Matteis, Stifel.

（操作員說明）Paul Matteis，Stifel。

Hi, thanks for taking our questions. This is Mark on for Paul. We were curious in just hearing if you can provide any color on the types of patients that are currently enrolling for the Phase III trials for fasedienol. That would be great. Thank you.

您好，感謝您回答我們的問題。這是保羅的馬克。我們很好奇您能否提供有關目前正在參加 fasedienol III 期試驗的患者類型的任何資訊。那太好了。謝謝。

Sure. Mark, thanks a lot. Josh, do you want to address that? Josh is on top -- primarily on top of our execution of the PALISADE program. Can you just give a brief insight, Josh?

當然。馬克，非常感謝。喬什，你想解決這個問題嗎？喬希（Josh）處於領先地位——主要是我們執行 PALISADE 計劃的領先者。喬什，可以簡單介紹一下嗎？

Yes. I mean it is very similar patients to those that were enrolled in our PALISADE-2 study. So from an inclusion/exclusion criteria, LSAS scores greater than 70 for example, no other kind of primary health disorders, no other primary mental health disorders. SAD would have to be primary those types of things. In addition, some of the exclusion criteria that we had incorporated were elimination of excessive smoking or vaping for instance, but it is typically primary SAD diagnosis with high enough severity. It is the typical patients that are coming in.

是的。我的意思是，這些患者與參加我們的 PALISADE-2 研究的患者非常相似。因此，從納入/排除標準來看，LSAS 得分大於 70，例如，沒有其他類型的原發性健康障礙，沒有其他原發性精神健康障礙。SAD 必須是主要的這些類型的事情。此外，我們納入的一些排除標準是消除過度吸煙或吸電子煙等，但這通常是嚴重程度足夠高的主要 SAD 診斷。進來的都是典型的病人。

Thank you.

謝謝。

Thanks, Josh. It is important. Obviously, we do quite a bit to ensure that we've got folks that properly meet the IE criteria. And we also obviously are focused on people with a disorder that's chronic. The typical onset with this disorder, as many people know is in adolescence.

謝謝，喬許。這很重要。顯然，我們做了很多工作來確保我們的人員能夠正確滿足 IE 標準。顯然，我們也關注患有慢性疾病的人。正如許多人所知，這種疾病的典型發病是在青春期。

And the duration is typically about 20 years. So you have people that obviously you want to get people involved who can be impacted by the medication. So we have a specific level set up to make sure that there is appropriate chronicity and severity. We also make sure that they haven't had any more recent medical issues that would have caused them to be ineligible for the study. But very high scrutiny and upfront in recruitment and lead generation and pre-screening, as well as making sure people are perfectly aligned with our IE criteria.

持續時間通常約為20年。所以你顯然想讓那些可能受到藥物影響的人參與其中。因此，我們設定了一個特定的級別，以確保有適當的長期性和嚴重性。我們也確保他們最近沒有出現任何可能導致他們沒有資格參加研究的醫療問題。但在招募、潛在客戶開發和預先篩選方面進行了非常嚴格的審查和預先審查，並確保人們完全符合我們的 IE 標準。

Thanks.

謝謝。

Andrew Tsai, Jefferies.

安德魯·蔡，杰弗里斯。

Hi, good afternoon. Thanks for the updates and thanks for taking my questions. So first one for PALISADE-3, are you by chance seeing higher screen failure rates compared to PALISADE-1 and 2? And is there anything else that you might be seeing in real time that gives you that extra boost of confidence you are doing the right thing, enrolling the right patients and executing the study even more rigorously than last time?

嗨，下午好。感謝您的更新並感謝您提出我的問題。那麼，第一個 PALISADE-3 的螢幕故障率是否比 PALISADE-1 和 2 更高？您即時看到的其他任何事情是否可以讓您更加自信，您正在做正確的事情，招募正確的患者並比上次更嚴格地執行研究？

Josh, do you want to give a little further insight on that?

喬希，你想進一步了解嗎？

Yes, absolutely. Thank you for the question. I think at this point, what we've seen in terms of green failure rates in terms of those that have a high enough score in the first public speaking challenge in terms of an anxiety score to move on to the second public speaking challenge, we've been pleasantly surprised that those rates have come in consistent with our projections. So we are seeing, again progress of the study that's in-line with expectations towards the targets that we've established. And so I think in general, really things going as expected there.

是的，絕對是。謝謝你的提問。我認為在這一點上，我們所看到的綠色失敗率，即那些在第一次公開演講挑戰中得分足夠高的人，在焦慮分數方面，可以繼續第二次公開演講挑戰，我們驚訝地發現這些比率與我們的預測一致。因此，我們再次看到研究的進展與我們設定的目標的預期一致。所以我認為總的來說，事情確實按照預期進行。

And then can you remind us how long it took for you to start in PALISADE-1 and 2 maybe PALISADE-1 and whether the enrollment cadence for PALISADE-3 is looking stronger or faster than the first thing?

然後您能否提醒我們您花了多長時間開始 PALISADE-1 和 2（也許是 PALISADE-1）以及 PALISADE-3 的註冊節奏是否看起來比第一件事更強或更快？

Andrew, thanks for the question. The enrollment cadence is on track with what we've guided. I mean, look obviously, the black swan and the pandemic impacted a lot of activity in 1 and 2, although we've been so pleasantly surprised not really surprised but expected and happy to see, is how normative the clinical development environment is now and how we are able to have a lot more predictability on the things that caused fits and starts in prior studies during the pandemic, especially PALISADE-1. So I can tell you that we are comfortable with the cadence and we're on track. Josh, anything else you want to add to that?

安德魯，謝謝你的提問。招生節奏符合我們的指導。我的意思是，顯然，黑天鵝和大流行影響了1 和2 中的許多活動，儘管我們感到非常驚喜，但並不是真的感到驚訝，而是預期和高興地看到，臨床開發環境現在是多麼規範，我們如何能夠對大流行期間先前研究中引起間歇性發作的因素有更多的可預測性，尤其是 PALISADE-1。所以我可以告訴你，我們對節奏感到滿意，而且我們正在步入正軌。喬什，你還有什麼要補充的嗎？

I think that captures it. The one thing I should have mentioned before was there is just a reminder that we have two public speaking challenges, right? So a key part of this study is the screen out at visit two and the first public speaking challenge of those subjects who don't have a high enough anxiety level to really show improvement. It is one of the things that differentiates our study.

我認為這抓住了它。我之前應該提到的一件事是提醒我們我們面臨兩個公開演講挑戰，對嗎？因此，這項研究的關鍵部分是在第二次訪視時進行篩選，並對那些焦慮程度不夠高而無法真正表現出改善的受試者進行第一次公開演講挑戰。這是我們的研究與眾不同的地方之一。

And it's not included as an exclusion, but it is a key piece of making sure that we have the right subjects moving forward to the randomization portion of the study. And those rates, those are critical for study execution. Those rates have been similar to what we observed in PALISADE-1 and PALISADE 2.

它不屬於排除項，但它是確保我們有正確的受試者進入研究隨機部分的關鍵部分。這些比率對於研究執行至關重要。這些比率與我們在 PALISADE-1 和 PALISADE 2 中觀察到的比例相似。

Great. Last question is, what's the latest on the PALISADE-2 publication, as well as a potential breakthrough designation filing? Thank you.

偉大的。最後一個問題是，PALISADE-2 出版物的最新情況以及潛在的突破性指定申請是什麼？謝謝。

Andrew, look we know obviously what we achieved in PALISADE-2 is historic. No one's ever done it. And so that's given rise to interest in terms of manuscript that we will be submitting to a journal that we believe is the best fit for that. That's in a very nice, mature stage of development.

Andrew，顯然我們知道我們在 PALISADE-2 中所取得的成就是歷史性的。從來沒有人做過。因此，這引起了人們對我們將提交給我們認為最適合的期刊的手稿的興趣。目前正處於一個非常好的、成熟的發展階段。

The other part of it is, look as you know, we've achieved Fast Track designation already. That's a serious and life-threatening indication. There is no question about that. What we achieved in PALISADE-2 is a very significant differentiator. And we'll see how it goes. There's never any guarantee you can make about any activity with the agency, but I like the chances that we have in fitting the profile that’s typically associated with moving beyond Fast Track.

另一部分是，如您所知，我們已經獲得了快速通道指定。這是一個嚴重且危及生命的跡象。毫無疑問。我們在 PALISADE-2 中所取得的成就是一個非常重要的差異化因素。我們會看看事情進展如何。對於與該機構的任何活動，您都無法做出任何保證，但我喜歡我們有機會符合通常與超越快速通道相關的個人資料。

Perfect. Thank so much for the color. Thanks.

完美的。非常感謝你的顏色。謝謝。

Tim Lugo, William Blair.

提姆·盧戈，威廉·布萊爾。

Thanks for the questions. And congratulations on the progress in the quarter. Can you remind us if you had discussions with the FDA about self-administration in PAL-1 and PAL-2 versus HCP administration in PAL-3 and PAL-4 and how you expect that to impact any dosing language in the label?

感謝您的提問。恭喜本季取得的進展。您能否提醒我們，您是否與FDA 就PAL-1 和PAL-2 中的自我給藥與PAL-3 和PAL-4 中的HCP 給藥進行了討論，以及您預計這將如何影響標籤中的任何劑量語言？

Sure. Thanks, Tim. Sure, we've obviously submitted the protocols to the agency, and they understand both of them. It is more consistent with what occurred in Phase II, the HCP administration of the single dose. So again, you are trying to ensure that you've got no variability site to site. So we don't think, it will impact anything associated with what we see at the end of the day, if we are successful in 3 or 4 combined with 2.

當然。謝謝，蒂姆。當然，我們顯然已經向該機構提交了協議，他們也理解這兩個協議。這與 II 期 HCP 單劑量給藥的情況更為一致。同樣，您要努力確保站點之間沒有差異。因此，我們認為，如果我們在第 3 項或第 4 項與第 2 項相結合方面取得成功，這不會影響我們最終看到的任何相關內容。

And that is for the acute treatment of SAD full stop and up to multiple times a day, four to possibly even six times a day given as you know, people have some days no stressor events and some days they have multiple different stressor events. So we see the ability for patients to be able to use the drug on demand. And that's consistent with the kind of discussions we've had with the agency in the past. So we want it to be an opportunity for people to have this drug in their backpack and their pocket to be able to, especially when they anticipate and predict stressors coming upon them, to be able to use it to knock down those symptoms at flare and cause them to not be able to either engage or to engage with all kinds of fear and disruptive anxiety and fearing embarrassment or humiliation.

這就是 SAD 的急性治療，每天最多進行多次，每天四次甚至六次，如您所知，人們有時沒有壓力源事件，有時則有多個不同的壓力源事件。因此，我們看到患者能夠按需使用該藥物的能力。這與我們過去與該機構進行的討論是一致的。因此，我們希望人們有機會將這種藥物放在背包和口袋裡，特別是當他們預期和預測壓力源即將降臨時，能夠使用它來消除這些突然發作的症狀，導致他們無法應對或應對各種恐懼和破壞性焦慮以及害怕尷尬或羞辱。

So we really do like, and I think that is part of why we are so comfortable with the patient-reported outcomes that are associated with the study design, both PGIC, as well as the SUDS on the front end. We want patients to be in control. And what we've shown in PALISADE-2 is that they can be in control. And the same thing now to replicate the efficacy of the drug just to ensure that you've got no potential variability with the use. We'll still do also a pretty normal human factor test downstream, but we don't see any issues.

所以我們真的很喜歡，我認為這就是為什麼我們對與研究設計相關的患者報告結果如此滿意的部分原因，包括 PGIC 和前端的 SUDS。我們希望患者能夠得到控制。我們在 PALISADE-2 中展示的是他們可以掌控一切。現在同樣的事情是複製藥物的功效，只是為了確保您在使用過程中沒有潛在的變異。我們仍然會在下游進行非常正常的人為因素測試，但我們沒有看到任何問題。

Okay. Maybe I missed this in the prepared commentary, but was there any granularity on the Phase 2b and MDD when that's going to be kicked off? Is that by year end?

好的。也許我在準備好的評論中錯過了這一點，但是 2b 階段和 MDD 何時啟動是否有任何詳細說明？是到年底嗎？

Not by year-end. Right now, we are working with some really good KOLs around the hoop on that program. And so we got a solid protocol synopsis that's developed. We're now moving that into the full protocol which we'll submit to the agency before the end of the year. And so we'll see how things progress on the other side of that.

到年底還不行。目前，我們正在與一些非常優秀的 KOL 一起參與這個專案。這樣我們就得到了一個可靠的協議概要。我們現在正在將其納入完整的協議中，並將在今年年底之前提交給該機構。因此，我們將看看事情的另一面進展如何。

Okay, thank you.

好的，謝謝。

(Operator Instructions) Madison Elsaadi, B. Riley Securities.

（操作員指示）Madison Elsaadi，B. Riley Securities。

Hi guys. Congrats on the progress you made. And thanks for taking my question. So a couple from me. Could you remind us PALISADE-3 will be performed at the same clinical size as PALISADE-3? And will we see top-line data from PALISADE-3 before dosing starts in PALISADE-4?

嗨，大家好。祝賀您的進步。感謝您提出我的問題。這是我的一對。您能否提醒我們 PALISADE-3 將在與 PALISADE-3 相同的臨床規模下進行？在 PALISADE-4 開始給藥之前，我們能否看到 PALISADE-3 的頂線資料？

So the first question is, will there be distinct sites in the studies? And the answer to that is yes. We'll have about 15, 16 sites per study, and we are not anticipating any overlap in the sites from the two studies. And then I'm not quite sure I heard the last part of the question, but if it was associated with when we will initiate PALISADE-4, is that what it was?

所以第一個問題是，研究中是否會有不同的地點？答案是肯定的。我們的每項研究將有大約 15、16 個站點，我們預計這兩項研究的站點不會有任何重疊。然後我不太確定我聽到了問題的最後一部分，但如果它與我們何時啟動 PALISADE-4 有關，那麼它就是這樣的嗎？

If we'll see top line data from PALISADE-3 before dosing starts in PALISADE-4.

如果我們在 PALISADE-4 中開始給藥之前看到 PALISADE-3 的頂線資料。

No. No. PALISADE-3 top-line data, both of those studies will read out in 2025. So currently, our target for PAL-3 is mid-25 and for PAL-4 will be near the end of '25. Every aspect of the PALISADE Phase III program, every single component of it, that remains associated with this US directed registration-directed program will be started this year and completed next year.

不。不。PALISADE-3 的頂線數據，這兩項研究都將於 2025 年讀出。因此，目前，我們 PAL-3 的目標是 25 年中，PAL-4 的目標是 25 年底左右。PALISADE III 期計劃的每個方面，其中的每個組成部分，仍與美國定向註冊計劃相關，將於今年啟動並於明年完成。

Got it. That's helpful. And then if I could ask, what are I guess, the gating steps to the MDD Phase IIb trial? And it looks like you guys have kind of reached the top of the dose efficacy curve with the current 6.4 microgram dose. Is that how you're looking at it? Or could that dose change?

知道了。這很有幫助。然後如果我可以問，我猜 MDD IIb 期試驗的門控步驟是什麼？目前 6.4 微克的劑量看起來你們已經達到了劑量功效曲線的頂部。你是這麼看的嗎？或者劑量可以改變嗎？

No, we think that's where we'll land. We saw some very nice success in the Phase IIa study at two different dose levels. And where I think we're landing on that one, again we are trying to finalize the protocol working with some of the KOLs you all have seen on our SAB, Maurizio Fava, Gerard Sanacora, Sanjay Mathew, Michael Liebowitz, all with long-term experience in depression. And what we see again with this drug, similar to obviously the way that we've achieved clinical success with the other pherine is to be able to get there through neurocircuitry focused MOAs that do not drive on to the same side effect and safety profile lane as we've typically seen every single drug that's out there.

不，我們認為那就是我們著陸的地方。我們在 IIa 期研究中看到了兩種不同劑量水平的一些非常好的成功。我認為我們正在解決這一問題，我們再次嘗試與你們在我們的 SAB 上見過的一些 KOL 一起敲定協議，其中包括 Maurizio Fava、Gerard Sanacora、Sanjay Mathew、Michael Liebowitz，他們都長期致力於——抑鬱症的長期經歷。我們再次看到這種藥物，顯然與我們使用另一種 pherine 取得臨床成功的方式類似，能夠透過以神經迴路為重點的 MOA 來實現這一目標，而 MOA 不會產生相同的副作用和安全性。正如我們通常看到的每一種藥物一樣。

And so what we think we can do here in a stand-alone monotherapy study will probably shoot it over six weeks with the 6.4 dose, double-blind, placebo-controlled, 1:1 randomization. We'll lean into Hamilton. HAMD-17 is the primary endpoint, just like we did in Phase II. A lot of that has to do with what we've seen with angst, depression and the benefits that we've seen there with this asset. So it will be a fairly conventional approach from an endpoint standpoint, and I think a 6-week program as we're looking at by twice a day dosing over 6 weeks at the 6.4 microgram level.

因此，我們認為我們可以在一項獨立的單一療法研究中做的事情可能會在六週內進行，採用 6.4 劑量、雙盲、安慰劑對照、1:1 隨機化。我們將傾向於漢密爾頓。HAMD-17 是主要終點，就像我們在第二階段所做的那樣。這在很大程度上與我們所看到的焦慮、憂鬱以及我們所看到的這項資產的好處有關。因此，從終點的角度來看，這將是一種相當傳統的方法，我認為我們正在研究的為期 6 週的計劃，每天兩次，在 6 週內以 6.4 微克的水平給藥。

Got it. Thank you.

知道了。謝謝。

Thank you. Ladies and gentlemen, there are no further questions. I would now hand the conference over to Mark McPartland for his closing comments. Mark?

謝謝。女士們先生們，沒有其他問題了。我現在將會議交給馬克·麥克帕特蘭（Mark McPartland）發表結束語。標記？

Thank you, operator, and thank you, everyone, for participating on the call today. If you have any other questions, please do not hesitate to contact us by e-mail at ir@vistagen.com or the Contact Us section of the website. We also encourage you to register for e-mail updates on the website to stay connected to the latest news and events for Vistagen. Thank you all again for participating on the call.

謝謝接線員，也謝謝大家參加今天的電話會議。如果您有任何其他問題，請隨時透過電子郵件 ir@visagen.com 或網站的「聯絡我們」部分與我們聯絡。我們也鼓勵您在網站上註冊電子郵件更新，以便隨時了解 Vistagen 的最新新聞和活動。再次感謝大家參與此次電話會議。

We appreciate everyone's interest and support. We look forward to keeping you updated on our ongoing progress. This concludes the call. Have a magnificent day.

我們感謝大家的關注與支持。我們期待向您通報我們的最新進展。通話就此結束。祝你有美好的一天。

Thank you. Ladies and gentlemen, the conference of Vistagen Therapeutics has now concluded. Thank you for your participation. You may now disconnect your lines.

謝謝。女士們、先生們，Vistagen Therapeutics 的會議現已結束。感謝您的參與。現在您可以斷開線路。