Vistagen Therapeutics Inc (VTGN) 2025 Q4 法說會逐字稿

Good day, everyone, and thank you for standing by. Welcome to the Vistagen Therapeutics fiscal year-end 2025 corporate update conference call and webcast. Please note that today's call is being recorded.

大家好，感謝您的收看。歡迎參加Vistagen Therapeutics 2025財年末公司更新電話會議及網路直播。請注意，今天的電話會議正在錄音中。

At this time, I'd like to turn the call over to your host, Mark McPartland, Senior Vice President, Investor Relations at Vistagen. Mark, please go ahead.

現在，我想把電話轉給主持人馬克·麥克帕特蘭 (Mark McPartland)，他是 Vistagen 公司投資者關係高級副總裁。馬克，請講。

Thank you, Victor. Good afternoon, everyone, and welcome to Vistagen's fiscal year-end 2025 corporate update conference call and webcast. Earlier this afternoon, we issued a press release for our fiscal year-end 2025, which ended on March 31, 2025, provided an overview of our progress across our lead clinical stage neuroscience programs. We encourage you to review the release and the 10-K, which can be found on our website's Investors section.

謝謝，維克多。大家下午好，歡迎參加Vistagen 2025財年公司更新電話會議和網路直播。今天下午早些時候，我們發布了一份關於2025財年（截至2025年3月31日）的新聞稿，概述了我們在臨床階段神經科學領域的主要專案進展。我們鼓勵您查看這份新聞稿和10-K報告，它們可以在我們網站的「投資者」版塊找到。

Before we begin, please note that we may make forward-looking statements regarding our business during today's call based on current expectations and information. These forward-looking statements speak only as of today, except as law requires. We do not assume any duty to update any forward-looking statements made today or in the future.

在開始之前，請注意，我們可能會在今天的電話會議上根據當前的預期和資訊就我們的業務做出前瞻性陳述。除非法律另有規定，否則這些前瞻性陳述僅代表截至今日的情況。我們不承擔更新今天或未來所做的任何前瞻性陳述的義務。

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 may make today. Additional information concerning risks and factors that could affect our business and financial results are included in our fiscal year-end 2025 Form 10-K for the period ending March 31, 2025 and in future filings, we'll make with the SEC from time to time, all of which are available in the Investors section of our website and on 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可能做出的任何前瞻性陳述所預期的結果有重大差異。有關可能影響我們業務和財務業績的風險和因素的更多信息，請參閱我們截至2025年3月31日的2025財年末10-K表格以及我們未來不時向美國證券交易委員會（SEC）提交的文件中。所有這些文件均可在我們網站的「投資者」板塊和SEC網站上查閱。

Now with the formalities out of the way, we warmly welcome our stockholders, sell-side analysts, and interested in our program and progress. I'm joined on our call today by Shawn Singh, our President and Chief Executive Officer; and Cindy Anderson, our Chief Financial Officer. Shawn will discuss recent highlights in our lead neuroscience program, and Cindy will discuss our fiscal year-end 2025 financial results. After our prepared remarks, there will be a brief opportunity for questions from the sell-side analysts on the call.

現在，正式儀式已結束，我們熱烈歡迎股東、賣方分析師以及對我們的專案和進度感興趣的各位。今天，我們的總裁兼執行長 Shawn Singh 和財務長辛蒂安德森 (Cindy Anderson) 也出席了我們的電話會議。肖恩將討論我們領先的神經科學計畫的最新亮點，辛蒂將討論我們2025財年末的財務表現。在我們準備好的發言之後，將有一個簡短的機會讓賣方分析師在電話會議上提問。

As a reminder, this call is being webcast and will be available for replay upon completion. A replay link can also be found on our website's Investor Events section.

小提醒：本次電話會議將進行網路直播，結束後可重播。重播連結也可在我們網站的「投資者活動」版塊找到。

I will now turn the call over to our President and Chief Executive Officer, Shawn Singh. Shawn, the field is yours.

現在，我將把發言權交給我們的總裁兼執行長 Shawn Singh。肖恩，現在輪到你了。

Thank you, Mark, and good afternoon, everyone. Thank you for joining us. As some of you know, our team here at Vistagen is at the leading edge of neuroscience that involves the therapeutic potential of nose-to-brain neuro circuitry, developing a new class of non-systemic intranasal product candidates called pherines. We now have five clinical-stage pherine product candidates, each with a mechanism of action, or MOA, that is differentiated from all approved drugs and positive results in a controlled trial.

謝謝馬克，大家下午好。感謝各位的參與。如各位所知，我們Vistagen團隊處於神經科學領域的前沿，致力於探索鼻腦神經迴路的治療潛力，正在開發一類名為「pherines」的新型非系統性鼻腔給藥候選產品。我們目前有五種處於臨床階段的pherines候選產品，每種產品的作用機制（MOA）都與所有已核准的藥物不同，並在對照試驗中取得了積極成果。

Together, they cover a broad and diverse range of large market conditions and disorders where underserved patients have needed new and better treatment options for many years. Fiscal 2025 was another significant year of progress across our neuroscience pipeline with multiple pherine product candidates in Phase II or Phase III development. We are advancing our mission to deliver transformative treatment options for patients and build value for our stockholders.

這些產品組合涵蓋了廣泛多樣的市場狀況和疾病，這些疾病多年來一直缺乏醫療服務，患者亟需新的、更優的治療方案。 2025財年是我們神經科學產品線又有一個重要進展的年份，多個Pherine候選產品已進入II期或III期開發階段。我們正在推進我們的使命，為患者提供變革性的治療方案，並為股東創造價值。

Our lead pherine product candidate, Fasedienol, is in Phase III development for the acute treatment of social anxiety disorder, or SAD. There is no FDA-approved acute treatment for SAD, a condition that now is estimated to affect over 31 million US adults who struggle with the intense stress and debilitating anxiety and fear of embarrassment, humiliation, and judgment in everyday social and performance situations. Our goal for Fasedienol is for it to become the first FDA-approved acute treatment of SAD and help improve the millions of Americans whose lives are affected by the serious and potentially life-threatening disorder that often brings -- begins in adolescence and occurs for decades beyond.

我們領先的非那雄胺候選產品 Fasedienol 正處於 III 期臨床開發階段，用於治療社交焦慮症 (SAD)。目前尚無 FDA 核准的 SAD 急性療法。據估計，目前有超過 3,100 萬美國成年人在日常社交和工作場合中飽受巨大壓力、令人痛苦的焦慮以及對尷尬、羞辱和評判的恐懼。我們的目標是讓 Fasedienol 成為首個獲得 FDA 批准的 SAD 急性療法，幫助數百萬受這種嚴重且可能危及生命的疾病影響的美國人改善生活。這種疾病通常始於青少年時期，並持續數十年。

The ongoing Phase III trials in our US registration-directed PALISADE program for Fasedienol for the acute treatment of SAD, PALSADE-3 and PALISADE-4, are designed to complement our success in our PALISADE-2 Phase III trial that we reported during the second half of 2023. Our PALSADE-3 trial is on track for a top-line data readout in the fourth quarter of this year. and we anticipate top line results from PALISADE-4 in the first half of 2026.

我們在美國註冊的PALISADE計畫中正在進行的用於治療SAD急性期的Fasedienol的III期試驗PALSADE-3和PALISADE-4，旨在補充我們在2023年下半年報告的PALISADE-2 III期試驗中取得的成功。我們的PALSADE-3試驗預計在今年第四季獲得頂線數據，我們預計PALISADE-4的頂線結果將於2026年上半年公佈。

The enthusiasm of patients and physicians participating in the PALISADE program continues to be very strong and we remain committed to a rigorous operational execution. If successful, we believe either PALISADE-3 or PALISADE-4, in combination with the positive results from PALISADE-2, could provide the substantial evidence of effectiveness needed to support a new drug application for Fasedienol and its potential to be the first FDA-approved acute treatment for SAD.

參與PALISADE計畫的患者和醫生的熱情持續高漲，我們始終致力於嚴格執行。如果成功，我們相信PALISADE-3或PALISADE-4，結合PALISADE-2的正面結果，能夠提供實質的有效性證據，支持Fasedienol的新藥申請，並有望成為首個獲得FDA批准的SAD急性治療藥物。

We are also advancing Itruvone, our pherine product candidate for standalone treatment of major depressive disorder, or MDD. Following the promising results from a controlled exploratory Phase IIa study we are encouraged by its differentiated non-systemic MOA and potential to treat MDD without the weight, gain, sexual side effects or systemic safety concerns commonly seen with traditional antidepressants.

我們也正在推進伊曲酮（Itruvone）的研發，這是我們的苯丙胺類候選藥物，用於單獨治療重度憂鬱症（MDD）。一項IIa期臨床探索性對照研究取得了令人鼓舞的結果，我們對其差異化非系統性作用機制（MOA）以及治療MDD的潛力感到鼓舞，並且不會出現傳統抗憂鬱藥物常見的體重增加、性副作用或系統性安全性問題。

Our pherine product candidate focused on women's health indications, PH80, also continues to generate interest as we advance this development as a potential hormone-free treatment for menopausal hot flashes. PH80 also demonstrated positive signals in the controlled exploratory Phase IIa study in premenstrual distort disorder, or PMDD, further validating its broad utility in women's health.

我們專注於女性健康適應症的候選產品 PH80 也持續受到關注，因為我們正在推進這項研發，將其作為治療更年期潮熱的潛在無激素療法。 PH80 在經前症候群（PMDD）的受控探索性 IIa 期研究中也顯示出正面的訊號，進一步驗證了其在女性健康領域的廣泛應用。

We are also encouraged by PH80's potential to treat the disruptive and painful effects of dysmenorrhea. We've made substantial progress preparing our US IND for PH80 to support additional Phase II clinical development in women's health, and we anticipate submitting the IND in the second half of this year.

PH80 在治療經痛帶來的紊亂和疼痛方面擁有巨大潛力，這令我們備受鼓舞。我們在 PH80 的美國臨床研究申請 (IND) 準備工作方面已取得重大進展，該申請將支持女性健康領域進一步的 II 期臨床開發，我們預計將於今年下半年提交 IND。

Beyond these three lead programs, our diversified pherine pipeline is potential for future to development to improve cognitive and psychomotor impairment due to mental fatigue as well as appetite enhancing effects in patients with cancer cachexia, often overlook conditions with limited treatment options. So across all five of our clinical-stage pherine product candidates, potential therapeutic benefit has been observed with favorable safety, a testament to the power and the promise of nose-to-brain neural circuitry.

除了這三個主要項目外，我們多元化的菲林產品線未來有望進一步發展，用於改善因精神疲勞導致的認知和精神運動障礙，以及增強癌症惡病質患者的食慾。這些疾病往往被忽視，且治療方案有限。因此，我們所有五個臨床階段的菲林候選產品均已觀察到潛在的治療益處，且安全性良好，這證明了鼻腦神經迴路的強大功能和前景。

On the US regulatory front, which is most of our minds these days, we are encouraged by the evolving regulatory landscape. Last week, I was privileged to participate in the FDA's CEO Listening Tour, was hosted at the Stanford Medical School. This CEO-only forum was led by FDA Commissioner, Dr. Marty Makary and CBER Director, Dr. Vinayak Prasad, and their supported staff members.

就我們最近最關注的美國監管方面而言，監管格局的不斷演變令我們感到鼓舞。上週，我有幸參加了在史丹佛醫學院舉辦的FDA CEO聆聽之旅。這場僅限CEO參加的論壇由FDA局長Marty Makary博士、CBER主任Vinayak Prasad博士及其支援團隊主持。

The forum was impressive and very productive, was allowed for essential direct interface between the new FDA leadership and my fellow industry CEOs to drive FDA initiatives that are designed to improve the ease and frequency of communication with the agency and provide clear and early guidance to support optimal capital allocation, enhance market confidence, and predictability, while also modernizing the agency's regulatory framework and leveraging AI to bring innovative, safe, and effective medications to underserved patient populations, both large and small.

該論壇令人印象深刻且富有成效，為 FDA 新領導層和我的同行行業首席執行官之間進行了必要的直接交流，推動了 FDA 的舉措，旨在提高與 FDA 溝通的便利性和頻率，並提供清晰和早期的指導以支持最佳資本配置，增強市場信心和可預測性，同時也使 FDA 的監管框架現代化，並利用人工智能為小藥物服務不足的患者為新的群體提供創新、安全群體。

So I applaud Commissioner Makary for holding this unique form in several cities across the country, where industry expertise and perspectives can and will be openly shared with FDA leadership. It's a meaningful step toward fostering a far more collaborative, transparent, and innovation-friendly regulatory environment where very importantly to us, new mechanisms of action and emerging technologies require reevaluation of legacy registrational pathways.

因此，我讚揚 Makary 局長在全國多個城市舉辦了這場獨特的研討會，讓行業專業知識和觀點能夠並與 FDA 領導層公開分享。這是朝著營造更具協作性、透明度和創新友善監管環境邁出的重要一步。對我們來說，至關重要的是，新的行動機制和新興技術需要重新評估傳統的註冊途徑。

At Vistagen, we welcome the conversations with the FDA as always, about policies that speed up in innovation and make drug development more efficient and affordable, and most importantly, improve patient outcomes.

在 Vistagen，我們一如既往地歡迎與 FDA 進行對話，討論加速創新、使藥物開發更有效率、更經濟的政策，最重要的是改善患者的治療效果。

Overall, we are energized by the potential of all five of our clinical-stage pherine product candidates. And with our primary focus on delivering top-line data from PALISADE-3 in the fourth quarter of this year, doing so has the near-term potential to transform lives and produce remarkable shareholder value.

總體而言，我們對所有五款臨床階段的苯丙胺酸候選產品的潛力充滿信心。我們的主要目標是在今年第四季交付PALISADE-3試驗的頂線數據，這在短期內有望改變人們的生活，並創造卓越的股東價值。

So I'll now turn the call over to our Chief Financial Officer, Cindy Anderson, to highlight some of our financial results for the year. Cindy?

現在我將把電話轉給我們的財務長辛蒂·安德森 (Cindy Anderson)，來重點介紹一下我們今年的一些財務表現。辛蒂？

Thanks, Shawn. As Shawn mentioned, I will highlight a few financial results from our fiscal year March 31, 2025. Research and development expenses were $39.4 million for the fiscal year ended March 31, 2025, compared to $20 million for the same period last year. The increase in R&D expenses was primarily due to increases in research, clinical and non-clinical development, contract manufacturing expenses, and headcount related to our US registrational PALISADE program for Fasedienol in SAD and our US IND-enabling program for PH80 in women's health.

謝謝，Shawn。正如Shawn所提到的，我將重點介紹我們截至2025年3月31日財年的一些財務表現。截至2025年3月31日的財年，研發費用為3,940萬美元，去年同期為2,000萬美元。研發費用的成長主要歸因於我們在美國註冊的PALISADE計畫（用於治療季節性憂鬱症的Fasedienol）以及美國女性健康領域PH80的IND-enabling計畫相關的研究、臨床和非臨床開發、合約生產費用以及員工人數的增加。

General and administrative expenses were $17.1 million for the fiscal year ended March 31, 2025, compared to $14.1 million for the same period last year. The increase in G&A expenses primarily due to increased headcount, consulting, and professional fees. Our net loss attributable to common shareholders was $51.4 million for the fiscal year ended March 31, 2025, compared to $29.4 million for the same period last year. As of March 31, 2025, we had $80.5 million in cash, cash equivalents, and marketable securities.

截至2025年3月31日的財年，我們的一般及行政費用為1,710萬美元，去年同期為1,410萬美元。一般及行政費用的增加主要由於員工人數增加、諮詢費用和專業費用增加。截至2025年3月31日的財年，我們歸屬於普通股股東的淨虧損為5,140萬美元，去年同期為2,940萬美元。截至2025年3月31日，我們擁有8,050萬美元的現金、現金等價物及有價證券。

I will now hand the call back over to Shawn.

我現在將把電話交還給肖恩。

Thank you, Cindy. Once again, everyone, at Vistagen, our mission is to transform lives with pioneering neuroscience and an innovative pipeline of intranasal product candidates, non-systemic intranasal product candidates that harness the power of nose-to-brain neurocircuitry, unlike any pharmaceutical product ever before them. With five promising clinical stage pherine product candidates and a US registration-directed Phase III program advancing, we're not just developing innovative potential treatments but also working to restore hope, dignity, and the quality of life for millions of people facing underserved conditions every day.

謝謝你，辛蒂。各位，Vistagen 的使命是利用先進的神經科學和一系列創新的鼻腔內用候選產品來改變人們的生活。這些非系統性鼻腔內用候選產品利用了鼻腦神經迴路的力量，這與以往任何藥物產品都不同。隨著五種前景看好的臨床階段苯丙胺酸候選產品和一個美國註冊指導的 III 期臨床試驗計畫的推進，我們不僅致力於開發創新的潛在治療方法，還致力於為數百萬每天面臨醫療資源匱乏的人們恢復希望、尊嚴和生活品質。

We thank you for your continued support and your belief in our mission. And on behalf of the entire Vistagen team, we're honored to be on this journey with you, and we look forward to keeping you closely updated on our continuing progress.

感謝您一直以來的支持以及對我們使命的信任。我謹代表Vistagen全體團隊，非常榮幸能與您攜手同行，並期待與您密切溝通我們的最新進展。

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

謝謝，Shawn。接線員，我們現在開始向今天參加會議的賣方分析師提問。

(Operator Instructions) Paul Matteis, Stifel.

（操作員指示）Paul Matteis，Stifel。

Hey, there, this is Julian on for Paul. Thanks so much for taking our questions. You alluded to changes with FDA leadership and there's been reports of turnover of staff and medical review teams. I guess in your interactions with the agency, have you noticed any changes or anything that's worth highlighting to sell-side and investors?

大家好，我是 Julian，接替 Paul。非常感謝您回答我們的問題。您提到了 FDA 領導層的變動，並且有報告指出員工和醫學審查團隊的人員變動。我想在您與該機構的互動中，您是否注意到了任何變化，或者有什麼值得向賣方和投資者強調的事情？

And then just with respect to PALISADE-4 quickly, you talked about patient demand being quite strong. What led to the modest slip back of timing for P4? Was it something operational? Or any color that you could provide on that would be super helpful.

關於PALISADE-4，您剛才提到患者需求非常旺盛。是什麼原因導致P4的治療時間略為延後？是操作方面的原因嗎？或者您能否提供一些細節，這將非常有幫助。

Great. You bet, Julian. So to the first question, it was a very common line of inquiry by a handful of us at that CEO listening forum. It was quite -- actually, it was interesting because it was a bit opposite of the tone and tenor that we had heard a week before in the open form at the Jefferies Conference.

太好了，沒錯，朱利安。所以，第一個問題，在CEO聆聽論壇上，我們幾個人常常會問。這相當——實際上，很有意思，因為它與我們一周前在傑富瑞大會的公開會議上聽到的語氣和基調略有不同。

And it was very encouraging, especially on this particular point. Not only did Dr. Makary say this, but also Dr. Prasad said it from the CBER voice, which is that no FDA reviewer or inspector was involved with the reduction in force, and that they are hiring additional reviewers and inspectors with domain expertise in the areas that they review.

這非常令人鼓舞，尤其是在這一點上。不僅Makary博士這麼說，Prasad博士也從CBER的角度表達了同樣的觀點，即FDA的審評員或檢查員沒有參與裁員，而且他們正在招聘更多在他們所審查領域擁有專業知識的審評員和檢查員。

So we hope that will be the case. I think in our case, we haven't seen any changes in our review team, which is helpful. One of the things I mentioned to them is it'd be nice and helpful to industry if at this point, given the kind of questions you just asked that each company, each sponsor with an open IND or a program that's underway gets reconfirmed that the team that they have is the team that they have had and especially as it relates to prior commitments and agreements. So we'll see if they act on that.

所以我們希望情況會如此。我認為就我們的情況而言，我們的審查團隊沒有任何變化，這很有幫助。我跟他們提到的一件事是，考慮到您剛才提出的問題，如果現在每家公司、每家擁有開放的IND或正在進行的專案的申辦方都能再次確認他們現有的團隊與之前相同，尤其是在與先前的承諾和協議相關的情況下，這將對行業發展大有裨益。所以我們拭目以待他們是否會採取行動。

But overall, I think we heard it not only at the Jefferies Conference, but again, at our listening forum, which is that in terms of the muscle, the reviewers, and the inspectors, there hadn't been any change. Most of the change associated with centralizing resources where there was tremendous overlap in fiefdoms and sort of a tribalism component where every aspect within the FDA had its own little universe, whereas none of us in the audience would really build the FDA or build a company like the FDA has been built today. So I think they appreciate that and recognize it. And I think we can expect some changes. So that's encouraging on that side.

但總的來說，我認為我們不僅在傑富瑞會議上聽到了這一點，而且在我們的聽證會上也聽到了這一點，那就是就權力、審查人員和檢查人員而言，沒有任何變化。大多數變化都與集中資源有關，導致部門之間出現大量重疊，並形成了一種部落主義的成分，FDA 內部的每個方面都有自己的小天地。而我們這些聽眾中，沒有人真正會去創建 FDA，或是創造像 FDA 這樣如今已經成立的公司。所以我認為他們欣賞並認識到了這一點。我認為我們可以期待一些改變。從這方面來看，這是令人鼓舞的。

So back to the PALISADE-4, I think overall, as I think we've talked to you and Paul about in the past and others, the enhancements that we brought to the table related to PALISADE-3, PALISADE-4 from lessons learned and improvements that could be implemented to limit variability, to enhance subject selection, to improve study execution efficiency, those kinds of things in addition to the mask, obviously coming off and eliminating some of the COVID-related disorders.

回到 PALISADE-4，我認為總的來說，正如我們過去與您和 Paul 以及其他人討論過的那樣，我們提出的與 PALISADE-3 和 PALISADE-4 相關的增強功能，吸取了經驗教訓，可以實施改進以限制變異性，增強受試者選擇，提高研究執行效率，除了口罩之外，顯然還可以摘下口罩並消除一些與 COVID 相關的疾病。

We really have been focused on very stringent subject eligibility requirements. And some of the original projections that we had were based on observations from PALISADE-2 and the recruitment rates in those studies, which steadily increase through the end of the study, especially when the world got a little bit more normal into PALISADE-2. And the impact of those positive enhancements that we made to PALISADE-3 and 4 wasn't really fully understood at the beginning, but it's now very apparent and screening visits have continued to increase and the more stringent subject eligibility requirements and secondary subject eligibility review that we integrated with developing our own internal team in addition to increasing training and remediation.

我們確實一直非常注重非常嚴格的受試者資格要求。我們最初的一些預測是基於對PALISADE-2的觀察以及這些研究中的招募率，這些招募率在研究結束時穩步上升，尤其是在PALISADE-2研究逐漸恢復正常之後。我們對PALISADE-3和PALISADE-4進行的積極改進的影響最初並沒有被完全理解，但現在已非常明顯。篩選訪問次數持續增加，更嚴格的受試者資格要求和二次受試者資格審查也與我們內部團隊的建設以及培訓和補救措施的加強相結合。

So bottom line, we've been very picky in the way that the study can be executed, the stringent inclusion-exclusion criteria all in an effort to, of course, replicate the success from PALISADE-2.

所以，歸根究底，我們對研究的實施方式非常挑剔，嚴格的納入和排除標準都是為了複製 PALISADE-2 的成功。

So I think we've got a pretty good rhythm now, and we've been able to eliminate subjects who we think may be less likely to demonstrate a benefit through that more rigorous eligibility criteria that we've applied and the secondary review of subject eligibility and site conduct that's ongoing and very specific. So overall, all that together has caused a little bit of an adjustment in timing, but we think that benefits the overall potential outcome of the study.

所以我認為我們現在的節奏相當不錯，而且我們能夠通過更嚴格的資格標準，以及持續且非常具體的對受試者資格和研究中心行為的二次審查，淘汰那些我們認為不太可能顯示出益處的受試者。總的來說，所有這些因素導致了時間上的一些調整，但我們認為這有利於研究的整體潛在結果。

Andrew Sai, Jefferies.

傑富瑞的安德魯賽。

Thanks for taking my question. Appreciate the updates. So looking ahead, heading into the PALISADE-3 data readout, can we expect you to announce enrollment completion in that study? And if so, from there, how many weeks can we expect you to take before reporting the top line data?

感謝您回答我的問題。感謝您的更新。那麼展望未來，在PALISADE-3數據公佈之前，我們能否期待您宣布該研究的入組工作完成？如果是的話，預計需要幾週時間才能公佈最終數據？

Thanks for the question, Andrew. So yes, we will report when we -- remember, it's a four-visit study paradigm. And so once the subjects have completed the randomized subjects have completed their safety follow-up, that's when we'll be announcing when the last patients completed that. And from that point forward, again, it always depends on the number of queries needed to get to DBL. But anywhere from us around six to top end would be eight weeks, but typically somewhere around 6 weeks to get to the top line from database lock.

謝謝你的提問，安德魯。是的，我們會在…的時候報告。記住，這是一個四次訪問的研究範例。因此，一旦受試者完成了隨機分組的安全隨訪，我們就會宣布最後一名患者完成隨訪的時間。從那時起，再次強調，這始終取決於進入DBL所需的查詢數量。我們通常需要大約六週，最長需要八週，但通常從資料庫鎖定到達到頂線需要大約六週的時間。

Understood. And then earlier speaking of variability back in the successful PALISADE-2 study, I think the placebo arm showed a SADs reduction of 8 points absolute basis. Would you expect that to be the same case for PALISADE-3 and 4? Or with these more enhanced controls could the placebo be lower?

明白了。先前提到在成功的 PALISADE-2 研究中出現的變異性，我認為安慰劑組的 SAD 絕對值降低了 8 分。您認為 PALISADE-3 和 PALISADE-4 也會出現相同的情況嗎？或者說，有了這些強化對照，安慰劑組的 SAD 會更低嗎？

Well, what we've certainly done, Andrew, is intended to design PALISADE-3 and 4 in a manner to replicate the success we saw in PALISADE-2. Where that actually lands, we'll have to see how the cards flip. But everything that we've done has been intended to limit variability. In any way, we can conceive of it after taking a look at PALISADE-1 and PALISADE-2 studies, which were the first two studies, as you know, with this design and this endpoint for the acute treatment of SAD. So a lot has been learned and the rigor matters.

嗯，安德魯，我們所做的當然是，旨在設計 PALISADE-3 和 PALISADE-4，以複製我們在 PALISADE-2 中看到的成功。最終效果如何，我們只能拭目以待。但我們所做的一切都是為了限制變異性。無論如何，在研究了 PALISADE-1 和 PALISADE-2 研究後，我們就能構思出最終方案。如你所知，這兩項研究是最早採用這種設計並以此為終點的 SAD 急性治療研究。因此，我們學到了很多東西，嚴謹性至關重要。

And so we'll see the idea, obviously, is to increased visibility into all aspects of the study and its execution to ensure the highest impossible potential to reduce variability. So hopefully, that falls in the direction that we saw things land with PALISADE-2.

因此，我們的想法顯然是提高研究及其執行各個環節的透明度，以確保最大限度地降低變異性。希望這能朝著我們在 PALISADE-2 計畫中看到的方向發展。

Great. And then my last question is in terms of site conduct and as well as your overall surveillance, are you making sure these PIs are disqualifying patients appropriately when these patients are taking their such tests? And are you looking at these sides rating somehow for each patient to make sure all time points make sense with the scoring?

太好了。我的最後一個問題是，就機構行為以及你們的整體監控而言，你們是否確保這些主要參與者在患者接受此類檢查時，能夠恰當地取消患者的資格？你們是否會以某種方式查看每位患者的各項評分，以確保所有時間點的評分都合理？

Well, the last question, again, whether it makes sense, they are what they are in terms of the scoring. But what I can tell you in the first hand, I mean, the whole purpose of what we did majorly differently with PALISADE-3 and 4 was to develop and have internally what we call our secondary eligibility review team. This is a team that internal Vistagen team, not a CRO team or a third-party team, but an internal team that consists of very experienced psychometricians who review eligibility of each subject, and they listen to screening assessments as well as each public speaking challenge to ensure in the proper execution.

嗯，最後一個問題，無論是否合理，就評分標準而言，它們都是這樣的。但我可以第一時間告訴你的是，我們在 PALISADE-3 和 PALISADE-4 中所做的重大改進，其目的是為了在內部組建一個所謂的二級資格審查團隊。這個團隊是 Vistagen 的內部團隊，不是 CRO 團隊或第三方團隊，而是由經驗豐富的心理測量學家組成的內部團隊，負責審查每個受試者的資格，並聆聽篩選評估以及每一次公開演講挑戰，以確保專案順利進行。

So we think, again, that those kinds of enhancements and those are some of the things that take a little bit more time. especially with obviously a hyperfocus on radar training upfront across all the endpoints, not just the subs, but the CGII and the PGIC. So that you have confidence that the study is being run the way it should be run and that we've done everything that we can through all the experience we've gained through the execution of two studies already to enhance the potential for success.

因此，我們再次認為，這些改進和改進需要更多時間，尤其是在所有終端（不僅是潛水艇，還包括CGII和PGIC）都高度重視雷達訓練的情況下。這樣才能確保研究能如預期進行，並確保我們已經盡一切努力，利用先前完成的兩項研究累積的經驗來提升成功的可能性。

(Operator Instructions) Myles Minter, William Blair.

（操作員指示） Myles Minter、William Blair。

I've got one on the CAR forum and maybe conversations that you had with Marty McCary. It seems pretty clear to me that the FDA is driven to try and expedite approvals of products that are addressing a health crisis in the US, the innovative cures for American People, addressing unmet public health needs, given the voucher program announced today, seems like your work in social anxiety to sort of would point to matching those pillars there.

我在CAR論壇上看到一篇，也許還有你和Marty McCary的對話。在我看來，FDA的動力顯然在於努力加速審批那些能夠應對美國健康危機的產品，那些造福美國人民的創新療法，以及那些尚未滿足的公共衛生需求。鑑於今天宣布的代金券計劃，你在社交焦慮方面的工作似乎在某種程度上與這些支柱相符。

But when we read the MAHA report that's coming from HHS, it paints a slightly different picture, at least in the preliminary stance there and the potentially want to restrict the use of mood stabilizer drugs. I know you're a different mechanism of action here. But did you get any sort of alignment from Marty or higher ups at the FDA that they're aligned with social anxiety disorder and Fasedienol all as meeting these FDA is mandated towards?

但是，當我們閱讀來自美國衛生與公眾服務部（HHS）的MAHA報告時，它描繪的景象略有不同，至少在初步立場上是如此，並且可能希望限制情緒穩定劑的使用。我知道你在這裡使用的是不同的作用機制。但是，你有沒有得到Marty或FDA高層的任何確認，他們與社交焦慮症和Fasedienol保持一致，因為滿足這些要求是FDA的強制性要求？

Or is there an alignment with the FDA here on that unmet need? Or is it more falling into that sort of opinion in that Maha report? I'd love your thoughts on that dynamic.

或者說，在未滿足的需求方面，FDA 的觀點是否一致？或者說，這比較符合 Maha 報告中的觀點？我很想聽聽您對此的看法。

And then secondly, it's a question on El and it seems clear to me that patient demand into the trial is not the issue here. Things are going well, but maybe it's the screening and the inclusion/exclusion criteria. I'm wondering whether that is to do with the [Libroid] social anxiety scale, and if it's more to do with the independent raters that you've got here that you didn't have before and whether they're screening out more patients?

其次，這是一個關於El的問題，在我看來，病人對試驗的需求顯然不是問題。目前進展順利，但問題可能出在篩選和納入/排除標準。我想知道這是否與[Libroid]社交焦慮量表有關，或者是否更多地與你們現在擁有的、以前沒有的獨立評估員以及他們是否篩選出了更多患者有關？

Well, thanks, Myles. It's quite a bit, and we could talk forever on that. But the first question, I think it's really important. I'd say, look, we got over 30 million people in this country that are affected by social anxiety. We've got a mechanism of action, unlike anything that's ever been put out in the anxiety arena.

嗯，謝謝，邁爾斯。這話題還蠻多的，我們可以一直聊下去。但我認為第一個問題非常重要。我想說，你看，我們國家有超過3000萬人受到社交焦慮的影響。我們找到了一種治療機制，與焦慮領域以往的任何方法都不一樣。

It's not a drug candidate that we see causing addiction potential, sexual side effects, weight gain, requiring a REMS, things that are just completely different than what the universe has seen before.

我們認為它不是一種會導致成癮性、性副作用、體重增加、需要 REMS 等症狀的候選藥物，這些症狀與宇宙以前見過的完全不同。

That said, in the forum, there was not -- one of the ground rules there was no specific conversations about your particular program. Everybody got a minute to talk. Most people didn't adhere to the minute but most people did adhere to not talking about their specific programs. So I can't give you the answer directly on that one from that context. We do think, of course, have Fast Track designation from FDA.

話雖如此，論壇的基本規則之一是，不要針對你的具體項目進行具體的討論。每個人都有發言時間。大多數人沒有遵守這一時間，但大多數人堅持不談論他們的具體項目。所以，我無法根據當時的情況直接回答你這個問題。當然，我們認為你獲得了FDA的快速通道資格。

So we do know what they think of it from a regulatory standpoint, serious and life-threatening. The prevalence continues to increase yet there aren't any new options that don't seem to have a whole bunch of baggage.

所以，從監管角度來看，我們知道他們是怎麼看待這個問題的：嚴重且危及生命。這種疾病的發生率持續上升，但似乎沒有任何新的治療方案能避免許多問題。

We certainly know about the benzo epidemic. So being able to deliver innovative MOAs certainly is on the mind of everybody in that room, FDA leadership, including some of the support team that I spoke with during the kind of the intro hour of that event. So I think we're confident for the place that we would be able to land in the universe associated with potential productivity people getting back into the rhythm of life that they aspire to achieve. There's ways to do that, and we know a lot of people are on the sidelines with SAD struggling with it mightily but yet simply saying, look, we don't want to delve into any of the other things that people might use to try to manage the disorder.

我們當然了解苯二氮類藥物的流行。因此，能夠提供創新的藥物作用機制（MOA）無疑是在場所有人的心頭好，包括FDA的領導層，以及我在活動開場時與之交流過的一些支持團隊。因此，我相信我們能夠在與潛在生產力相關的領域中佔有一席之地，幫助人們重回他們渴望實現的生活節奏。有很多方法可以做到這一點，我們知道很多人在SAD的困擾下苦苦掙扎，卻只是簡單地說，看，我們不想深入研究人們可能用來控制這種疾病的任何其他方法。

So I think, again, anything that's going to provide a beneficial patient outcome with negligible risk on the safety side is something that the FDA is going to be open to looking at, and we've seen that consistently regardless of whose the commissioner. I don't think that changes. In terms of your question about PALISADE-3 and 4. Really what's different is it's not at the top of the funnel at all. We've seen incredible interest in our recruitment vehicles.

所以我認為，任何能為患者帶來有益結果且安全風險可忽略不計的藥物，FDA 都會持開放態度進行審查。無論誰是局長，我們都一直看到這一點。我認為這不會改變。關於你關於 PALISADE-3 和 4 的問題，真正的不同之處在於，它根本不是漏斗頂端。我們看到人們對我們的招募工具表現出極大的興趣。

But where we have seen things slow is the visit one, the screening upfront of a visit one. The throughput rates from the screening visit through the end of the study have been very much what we saw in prior studies.

但我們發現進展緩慢的地方是訪視階段，也就是訪視前的篩檢階段。從篩檢訪視到研究結束的吞吐量與我們先前的研究結果基本一致。

We also have seen a remarkably good throughput rate from visit 4 into the open label. Those are the kinds of things we like to see. And we tend to not see any of the kind of hockey stick utilization that worries folks about abuse liability either. Remember, FDA said we didn't have to do a human abuse liability study at that time and always seen hence is concordant safety data and studies completed. So it's really more about the scrutiny associated with eligibility inclusion exclusion and the eligibility criteria at the very front end of the study to make sure that we've got folks that are sufficiently affected by the disorder aren't associated with any other comorbidities that would be exclusions associated with enrollment and obviously, making sure that they're screened out rigorously for any con meds.

從第4次訪視到開放標籤試驗，我們也看到了非常高的吞吐率。這些都是我們樂見的。而且，我們通常也不會看到任何令人擔憂濫用責任的曲棍球棒式用藥。記住，FDA 當時表示我們不必進行人體濫用責任研究，因此我們始終能看到一致的安全數據和已完成的研究。所以，這實際上更多是關於資格、納入和排除的審查，以及研究初期的資格標準，以確保我們招募的受試者受該疾病的嚴重影響，並且沒有任何其他可能被排除在入組範圍之外的合併症，當然，還要確保他們經過嚴格的篩檢，排除任何與藥物相關的成分。

So it's mostly, again, from at the pre-visit 1 screening where we've seen a little bit of a slowdown, but that itself is also starting to pick up.

因此，主要是在第一次就診前的篩檢中，我們看到了一點放緩，但本身也開始回升。

Operator, I believe that's all the time we have for questions today. If you have -- if those participated on the call of additional questions, please don't hesitate to contact us by e-mailing ir.tvistagen.com or via the contact section of our website. We also encourage you to register for e-mail updates on our website to stay connected with our latest news.

接線員，我想今天的問題解答時間就到這裡了。如果您——或參與了電話會議的各位——還有其他問題，請隨時透過電子郵件 ir.tvistagen.com 或我們網站的聯絡頁面與我們聯絡。我們也建議您在我們的網站上註冊電子郵件更新，以便隨時了解我們的最新消息。

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

感謝您今天的電話會議。我們感謝大家的關注與支持。我們期待隨時向您通報我們的進展。電話會議到此結束。祝您擁有美好的一天。

Thank you for your participation in today's conference. This concludes the program. You may now disconnect. Everyone, have a great day.

感謝大家參加今天的會議。今天的節目到此結束。現在您可以斷開連線了。祝大家有愉快的一天。