Protagenic Therapeutics Inc (PTIX) 2023 Q4 法說會逐字稿

Greetings. Welcome to the Protagenic Therapeutics' fourth-quarter and fiscal year 2023 earnings call. (Operator Instructions)

問候。歡迎參加 Protagenic Therapeutics 2023 財年第四季和財報電話會議。（操作員指示）

Please note this conference is being recorded.

請注意，本次會議正在錄製。

I will now turn the conference over to your host, Alex Arrow. You may begin.

現在我將會議交給主持人亞歷克斯·阿羅 (Alex Arrow)。你可以開始了。

Thank you very much. Good afternoon, everyone. I'd like to welcome you to Protagenic Therapeutics' earnings call to review our fourth-quarter and fiscal year 2023 year-end operating results.

非常感謝。大家下午好。歡迎您參加 Protagenic Therapeutics 的收益電話會議，回顧我們第四季和 2023 財年的年終營運表現。

Participating on the call today with me is our Executive Chairman, Dr. Garo Armen; our Chief Operating Officer, Dr. Andrew Slee; and our Chief Medical Officer, Dr. Bob Stein. I'd like to thank them and each one of you for your time and commitment to Protagenic Therapeutics.

今天與我一起參加電話會議的有我們的執行主席 Garo Armen 博士、我們的營運長 Andrew Slee 博士和我們的首席醫療官 Bob Stein 博士。我要感謝他們以及你們每個人為 Protagenic Therapeutics 付出的時間和承諾。

I'm the company's Chief Financial Officer, Alexander Arrow. 2023 was a pivotal year in the history of our company. During 2023, we began our first ever clinical trial of our lead product, known as PT00114, a drug candidate that has the potential to benefit millions of patients suffering from depression, chronic anxiety, PTSD, or drug addiction.

我是公司的財務長亞歷山大·阿羅。 2023 年是我們公司歷史上關鍵的一年。2023 年，我們開始了主導產品 PT00114 的首次臨床試驗，該產品是一種候選藥物，有可能使數百萬患有憂鬱症、慢性焦慮症、創傷後壓力症候群或藥物成癮的患者受益。

On today's call, we'll be providing a detailed discussion about the significance of this clinical trial and an outlook for what to expect specifically in 2024. Before we begin those remarks, I'd like to note that the following commentary will include some forward-looking statements that are subject to risks and uncertainties that may cause actual results to differ materially from those that we forecast.

在今天的電話會議上，我們將詳細討論此次臨床試驗的意義以及 2024 年具體情況的展望。在我們開始這些評論之前，我想指出的是，以下評論將包括一些前瞻性陳述，這些陳述受風險和不確定性的影響，可能導致實際結果與我們的預測有重大差異。

Forward-looking statements include statements regarding the field of neuroactive peptides and the potential for therapies to have a quantifiable effect on anxiety, depression, PTSD, or addiction; the expectation that TCAPs will become accepted treatment regimens for neurologic disease conditions and potentially replace less effective antidepressant, anti-anxiety, or anti-addiction therapies as the standard of care; the development, regulatory, and commercialization efforts, and the timeliness of the company's PT00114 drug candidate or any licensees or partners; the potential for our single neuropeptide drug candidate to reduce the severity of disorders that has been targeted to treat; the potential for the company to bring in funding either by monetizing some of its potential future royalty streams, or executing a new strategic collaboration or by selling stock at a price per share that is higher than current levels; and other forecasts of future events.

前瞻性陳述包括關於神經活性勝肽領域以及療法對焦慮、憂鬱、創傷後壓力症候群或成癮產生可量化影響的潛力的陳述；TCAP 將成為神經系統疾病的公認治療方案並可能取代效果較差的抗憂鬱、抗焦慮或抗成癮療法作為治療標準的預期；公司 PT00114候選藥物或任何被許可人或合作夥伴的開發、監管和商業化努力以及及時性；我們的單一神經肽候選藥物降低目標治療疾病嚴重程度的潛力；公司通過將部分潛在的未來特許權使用費流貨幣化、執行新的戰略合作或以高於當前水平的每股價格出售股票來籌集資金的潛力；以及對未來事件的預測。

These risks and uncertainties include but are not limited to those identified under the heading risk factors in our annual report on Form 10-K for the year ended December 31, 2023, which has been filed today with the SEC.

這些風險和不確定性包括但不限於我們今天向美國證券交易委員會提交的截至 2023 年 12 月 31 日的年度報告 10-K 表格中風險因素標題下所確定的風險和不確定性。

And now I'd like to introduce you to Dr. Garo Armen, the company's Executive Chairman, to make opening remarks and frame today's discussion. After the discussion of our clinical progress and outlook, I will come back and review our financial performance in Q4 and fiscal year 2023. And then Garo will open the call up to your questions. Garo?

現在，我想向大家介紹公司執行董事長加羅·阿曼博士 (Garo Armen)，他來致開幕詞並主持今天的討論。在討論了我們的臨床進展和前景之後，我將回來回顧我們第四季度和2023財年的財務表現。然後 Garo 將開始回答大家的問題。加羅？

Thank you very much, Alex. I'm excited to share with you the progress that we've made with Protagenic Therapeutics in 2023. As we transform the company into a clinical-stage company with the initiation of our first in-human trial of PT00114.

非常感謝，亞歷克斯。我很高興與大家分享我們在 2023 年與 Protagenic Therapeutics 合作的進展。隨著我們啟動 PT00114 的首次人體試驗，我們將公司轉變為臨床階段公司。

This drug candidate, which is an analogue of the naturally occurring neuropeptide, teneurin C-terminal associated peptide, otherwise known as TCAP, works through a novel mechanism of action distinct from currently available treatments for neuropsychiatric disorders.

這種候選藥物是天然存在的神經肽、神經肽 C 端相關肽（也稱為 TCAP）的類似物，其作用機制不同於目前治療神經精神疾病的藥物。

PT00114 precisely targets specific neuronal path peptides or pathways involved in the stress response and emotional processing, with the potential to restore a healthy brain function and provide relief to patients suffering from anxiety, possibly depression, PTSD, and addiction.

PT00114 精確針對與壓力反應和情緒處理相關的特定神經通路勝肽或通路，有可能恢復健康的大腦功能並為患有焦慮症、憂鬱症、創傷後壓力症候群和成癮症的患者提供緩解。

By working in harmony with the brain's innate regulatory systems, PT00114 may deliver meaningful improvements in symptoms and quality of life with fewer side effects compared to existing medications. And of course, the field knows a lot of the limitations of existing medications.

透過與大腦先天調節系統協調工作，PT00114 可以顯著改善症狀和生活質量，並且與現有藥物相比副作用更少。當然，該領域知道現有藥物的許多限制。

As you will hear in more detail from Dr. Stein and Dr. Slee, our extensive preclinical research provides a robust foundation for the clinical development of our agent. We believe this groundbreaking therapy could transform the treatment landscape and bring new hope to millions of people, as Alex alluded to, living with the burden of undertreated and debilitating mental health conditions.

正如您將從 Stein 博士和 Slee 博士那裡聽到的更詳細的資訊一樣，我們廣泛的臨床前研究為我們的藥物的臨床開發提供了堅實的基礎。我們相信，這種突破性的療法可以改變治療格局，並為數百萬因治療不足和精神健康狀況惡化而承受負擔的人帶來新的希望，正如亞歷克斯所提到的。

I'd now like to introduce Dr. Bob Stein, the company's Chief Medical Officer, to share with you more details. Bob?

現在我想介紹公司首席醫療官鮑伯‧史坦博士，與大家分享更多細節。鮑伯？

Hello, everyone. In the quest to address the complexities of neuropsychiatric disorders, our focus at Protagenic Therapeutics has been to delve deeply into the mechanisms that underpin our responses to stress and its profound impact on mental health.

大家好。為了解決神經精神疾病的複雜性，Protagenic Therapeutics 的重點是深入研究我們應對壓力的機制及其對心理健康的深遠影響。

Central to our efforts is PT00114, a synthesized analogue of tenuerin C-terminal associated peptide or TCAP, discovered through the pioneering work of our Scientific Founder, Dr. David Lovejoy. This groundbreaking therapy acts broadly in the brain with notable effects in the amygdala, the critical brain region involved in emotional processing and stress response, marking a significant advance over alternative therapies.

我們努力的核心是 PT00114，它是 tenuerin C 端相關勝肽或 TCAP 的合成類似物，由我們的科學創始人 David Lovejoy 博士透過開創性工作發現。這種突破性的療法廣泛作用於大腦，對杏仁核（大腦中負責情緒處理和壓力反應的關鍵區域）有顯著的影響，這標誌著它比替代療法有了顯著的進步。

Our journey has been guided by a rigorous scientific inquiry, revealing that the stress induced maladaptations in brain function extend beyond mere symptoms to the very core of neuropsychiatric conditions. The preclinical data on PT00114 offer compelling evidence of its capacity to directly modulate brain responses to stress, including modulating limbic and amygdala activity.

我們的旅程以嚴謹的科學探究為指導，揭示了壓力引起的大腦功能不適應不僅僅是症狀，而是神經精神疾病的核心。PT00114 的臨床前數據提供了令人信服的證據，證明其能夠直接調節大腦對壓力的反應，包括調節邊緣和杏仁核活動。

This targeted approach not only promises to mitigate the symptoms of anxiety, depression, PTSD, and addiction, but also aims to address the underlying causes of these conditions by restoring neuronal and behavioral balance.

這種有針對性的方法不僅有望減輕焦慮、憂鬱、創傷後壓力症候群和成癮的症狀，而且還旨在透過恢復神經和行為平衡來解決這些疾病的根本原因。

Unlike broad-spectrum therapies that affect the brain in a more generalized manner, PT00114's precise action on specific neural pathways represents a refined strategy. It holds the potential to improve therapeutic outcomes by engaging with the brain's natural mechanisms for managing stress responses and emotion. This specificity suggest greater efficacy with fewer side effects, aligning closely with the evolving needs of patient care and mental health.

與以更普遍的方式影響大腦的廣譜療法不同，PT00114 對特定神經通路的精確作用代表了一種精細的策略。它有可能透過與大腦管理壓力反應和情緒的自然機制相結合來改善治療效果。這種特異性顯示療效更高、副作用更少，與患者護理和心理健康不斷變化的需求緊密結合。

Now that we have advanced PT00114 into clinical development, the exciting path forward presents a wide range of opportunities. Our preclinical data support the potential of PT00114 to treat anxiety, depression, post-traumatic stress disorder, drug addiction, and even conditions such as neurodegeneration.

現在我們已經將 PT00114 推進到臨床開發階段，令人興奮的前進之路帶來了廣泛的機會。我們的臨床前數據支持 PT00114 治療焦慮、憂鬱、創傷後壓力症候群、藥物成癮甚至神經退化性疾病等疾病的潛力。

Our challenge has been to focus and prioritize the indications we explore. The depth of our preclinical insights, underscored by a nuanced understanding of TCAP's role in stress regulation, sets a solid foundation for our clinical trials.

我們的挑戰是集中精力並優先考慮我們探索的跡象。我們對臨床前洞察的深度，以及對 TCAP 在壓力調節中的作用的細緻理解，為我們的臨床試驗奠定了堅實的基礎。

Collaborating with experts like Dr. Maurizio Fava, Harvard University's Psychiatrist-in-Chief and leveraging robust pharmacological and safety profiles, they have initiated clinical trials that are poised to explore PT00114's potential in selected neuropsychiatric disorders.

他們與哈佛大學首席精神科醫生 Maurizio Fava 博士等專家合作，利用強大的藥理學和安全性概況，啟動了臨床試驗，準備探索 PT00114 在特定神經精神疾病中的潛力。

The implications of our work extends beyond the immediate horizon of drug development. They invite a reevaluation of how we understand and treat neuropsychiatric disorders, emphasizing the need for interventions that tap into and amplify the body's own regulatory systems.

我們的工作意義深遠，不僅限於藥物開發的直接範圍。他們呼籲重新評估我們理解和治療神經精神疾病的方式，並強調需要採取乾預措施來利用和增強人體自身的調節系統。

In closing, our commitment to uncovering the therapeutic potential PT00114 is unwavering. This centers not just about advancing a promising drug candidate, it's about fostering a deeper understanding of mental health and offering hope to the many people afflicted by stress-related conditions.

最後，我們堅定不移地致力於發掘 PT00114 的治療潛力。這不僅是為了推進有前景的候選藥物，也是為了加深對心理健康的了解，並為許多受到壓力相關疾病困擾的人帶來希望。

Thank you for your attention. I will be happy to take any questions you might have about our work at the end of the formal session.

感謝您的關注。在正式會議結束時，我很樂意回答您有關我們工作的任何問題。

Now I'd like to introduce you to my colleague, Dr. Andy Slee, Protagenic's Chief Operating Officer. Andy?

現在我想向大家介紹我的同事，Protagenic 的營運長 Andy Slee 博士。安迪？

Thank you very much, Bob. I'm here today as part of a team deeply committed to transforming the way we approach mental health treatment. Our work with PT00114 provides an unprecedented opportunity to bring best-in-class treatment to people suffering from a broad range of mental disorders.

非常感謝，鮑伯。今天，我作為團隊的一員來到這裡，致力於改變我們對待心理健康治療的方式。我們對 PT00114 的研究提供了前所未有的機會，為患有各種精神疾病的人提供一流的治療。

We have demonstrated preclinically that TCAP is both potent and safe, and that it has beneficial effects to combat the negative effects of stress. It also has, unlike other CNS acting agents, a very rapid onset and also has a long duration even after a single dose.

我們已經在臨床前證明，TCAP 既有效又安全，對抗擊壓力的負面影響有益。與其他作用於中樞神經系統的藥物不同，它起效非常快，即使單次服用後藥效也能持續很長時間。

We have shown that TCAP is effective after injection, either subcutaneously or intravenously, and that it can be used after placement under the tongue or delivery intranasally. Unlike benzodiazepines such as Valium, it doesn't cause sedation.

我們已經證明 TCAP 注射後有效，無論是皮下注射還是靜脈注射，都可以放在舌下或經鼻腔內使用。與安定等苯二氮平類藥物不同，它不會引起鎮靜。

Furthermore, it does not seem to impact weight gain or impact libido, and we have demonstrated with other classic agents that it does not have the addictive potential of fentanyl or other type agents. And that was carried out by an independent CRO.

此外，它似乎不會影響體重增加或影響性慾，我們已經透過其他經典藥物證明它不具有芬太尼或其他類型藥物的成癮性。這項工作由一位獨立的 CRO 完成。

In unstressed animals, it can be delivered by a whole variety of routes, as I said, and this gives us an opportunity to ensure that we have compliance with patients. Our synthetic analogue, PT00114, actually represents a convergence of natured wisdom and along with -- we'll take some credit a little bit of scientific innovation.

正如我所說，在不受壓力的動物中，它可以透過多種途徑傳遞，這使我們有機會確保患者的依從性。我們的合成類似物 PT00114 實際上代表了自然智慧的融合，同時也體現了一點科學創新。

This peptide is actually conserved across a fast evolutionary landscape, spanning from nematodes to humans. And this suggests it plays an integral role in CNS function potentially without eliciting toxicities, as seen with other agents that are commonly given for mental disorders.

這種勝肽實際上在從線蟲到人類的快速進化景觀中得到了保存。這表明它在中樞神經系統功能中起著不可或缺的作用，而不會引起毒性，就像其他常用於治療精神障礙的藥物一樣。

Our approach been grounded in an extensive GLP toxicological study as well as preclinical studies. And we have used both rodents and non-human primates, and we have found that we have a very broad therapeutic window. This provides us a solid foundation for moving our application into humans.

我們的方法以廣泛的 GLP 毒理學研究以及臨床前研究為基礎。我們利用囓齒動物和非人類靈長類動物進行了研究，發現我們的治療窗口非常廣闊。這為我們的應用在人類身上提供了堅實的基礎。

As we prepare to test this agent in patients, we have focused on understanding its pharmacology, particularly with focus on developing useful transitional approaches to facilitate its movement from bench to bedside. We've evaluated effects required for an efficacious dose given by various routes and different dosing schedules, so that we can optimize our clinical development path.

當我們準備在患者身上測試這種藥物時，我們專注於了解其藥理學，特別是專注於開發有用的過渡方法以促進其從實驗室到臨床的轉移。我們評估了透過各種途徑和不同的給藥方案給予有效劑量所需的效果，以便我們能夠優化臨床開發路徑。

The operational challenge and our solution has been to navigate the complex transitional landscape from bench to bedside. The administration route to have meticulously selected, as I said, to enhance compliant and accessibility, ensuring that the therapeutic potential of TCAP is fully realized.

營運挑戰和我們的解決方案是應對從實驗室到臨床的複雜過渡環境。正如我所說，給藥途徑要經過精心選擇，以提高依從性和可及性，確保充分發揮 TCAP 的治療潛力。

We're excited to explore the effects of PT00114 in patients, anticipating that we will be able to recapitulate very promising activities we have seen in our preclinical models.

我們很高興探索 PT00114 對患者的影響，期望我們能夠重現我們在臨床前模型中看到的非常有希望的活動。

In the realm of clinical of development, we have currently under evaluation in SAD, which is a single ascending dose; and MAD, multiple ascending dose studies, involving normal healthy volunteers. These studies are crucial as they help us delineate the efficacious dosing regimen that will be required in humans.

在臨床開發領域，我們目前正在對 SAD（單次遞增劑量）和 MAD（多次遞增劑量研究）進行評估，涉及正常健康志願者。這些研究至關重要，因為它們幫助我們確定人類所需的有效給藥方案。

Unlike many current drugs that treat mental illness, the dose response of PT00114 is actually well defined and the drug is very safe. Therefore, the challenges in navigating the delicate balance between efficacy and safety as seen with other treatment appears not to be that problematic with PT00114. The progress in these clinical trials are not just measured by its potential, but testament to our rigorous approach in a patient-centric development.

與目前許多治療精神疾病的藥物不同，PT00114 的劑量反應實際上是明確的，而且藥物非常安全。因此，其他治療方法所面臨的在療效和安全性之間取得微妙平衡的挑戰對於 PT00114 來說似乎不那麼成問題。這些臨床試驗的進展不僅以其潛力來衡量，而且證明了我們以患者為中心的開發中嚴謹的方法。

Our insights into the molecule's performance in both acute and chronic model to stress underscore a significant leap over traditional small molecule CRF antagonist. Unlike these antagonists, CRF or corticotroponin releasing factor, PT00114 maintains its activity across a range of stress-induced conditions that are relevant animal models.

我們對該分子在急性和慢性壓力模型中的表現的洞察凸顯了其比傳統小分子 CRF 拮抗劑有了顯著的飛躍。與這些拮抗劑 CRF 或促皮質素釋放因子不同，PT00114 在一系列相關動物模型的壓力誘發條件下維持活性。

And whereas the normal, these small molecule CRF antagonist do not perform in chronic models, PT00114 does. It blocks -- to them -- we found that both PT00114 and direct CRF blockers work in animal models, as I've said.

而正常的這些小分子 CRF 拮抗劑在慢性模型中不起作用，而 PT00114 卻起作用。它阻斷了——對它們來說——我們發現 PT00114 和直接 CRF 阻斷劑都在動物模型中起作用，正如我所說的那樣。

But the distinction is that we work in a chronic distress model and in patient is to chronic stress conditions, not necessarily the acute stress condition that drives the disorders to mental health like anxiety and depression.

但差別在於，我們是在慢性痛苦模型中工作的，而患者所面對的是慢性壓力狀態，而不一定是導致焦慮和憂鬱等精神健康障礙的急性壓力狀態。

This important difference that we have discovering the efficacy of PT00114 compared with direct CRF blocking has reassured us that we're bringing forward a very important new medicine. As we continue on this path, the strides we're make in chemical characterization of the effect of the stage in selected mental disorders are pivotal.

我們發現 PT00114 的功效與直接 CRF 阻斷相比具有重要差異，這使我們確信我們正在推出一種非常重要的新藥。隨著我們繼續沿著這條道路前進，我們在對特定精神障礙的階段影響進行化學表徵方面所取得的進展至關重要。

They represent our commitment to reshaping the landscape of the treatment of anxiety, depression, PTSD, as well as addiction. We thank you for your support and our belief in our mission. And together, we are stepping into a new era of mental health treatment marked by innovation, compassion, unwavering commitment to improving patients' lives.

它們代表了我們致力於重塑焦慮、憂鬱、創傷後壓力症候群以及成癮治療領域的決心。我們感謝您的支持以及對我們使命的信任。我們正攜手邁入心理健康治療的新時代，這一時代以創新、同情和堅定不移地致力於改善患者生活為標誌。

With that, I thank you and turn it over to Alex Arrow.

最後，我感謝您，並將發言權交給 Alex Arrow。

Thank you very much, Andy. As you can see from our clinical trial status, the company made operational progress towards its primary objective of developing and commercializing PT00114 during fiscal year 2023, particularly during the fourth quarter. Our financial results reflect an increase in R&D spending to pursue that goal.

非常感謝，安迪。從我們的臨床試驗狀態可以看出，公司在 2023 財年，尤其是在第四季度，朝著開發和商業化 PT00114 的主要目標取得了營運進展。我們的財務結果反映出我們為實現這一目標而增加了研發支出。

In the fourth quarter of 2023, we spent $1.0 million on R&D, which is an increase of 301% over the $258,000 R&D that we spent in the fourth quarter of 2022. This significant increase in R&D expenditures was entirely due to the clinical trial that is now in progress, which commenced just as Q4 was starting.

2023 年第四季度，我們在研發上花費了 100 萬美元，比 2022 年第四季花費的 258,000 美元增加了 301%。研發支出的大幅增加完全歸功於目前正在進行的臨床試驗，該試驗於第四季度開始時啟動。

Our general and administrative spend for the fourth-quarter 2023 was just $201,000, which is down 50% from our R&D spend in the comparable quarter a year ago, primarily because we issued no stock options during the quarter. And we had no non-cash competition or minimal non-cash compensation expense during the quarter as we previously had in the fourth quarter of 2022.

我們 2023 年第四季的一般和行政支出僅為 201,000 美元，比去年同期的研發支出下降了 50％，主要是因為我們在本季沒有發行股票選擇權。與 2022 年第四季一樣，本季我們沒有遇到非現金競爭，也沒有出現極少的非現金薪資支出。

As for sales and marketing, we spent none in either the fourth quarter of '23 nor the fourth quarter 2022, as we're not in the market yet. Overall, our net loss for Q4 was $1.2 million compared to a net loss of $656,000 a year-ago quarter.

至於銷售和行銷，我們在 2023 年第四季和 2022 年第四季都沒有花費任何資金，因為我們還沒有進入市場。總體而言，我們第四季的淨虧損為 120 萬美元，而去年同期的淨虧損為 65.6 萬美元。

For the full-year 2023, we spent $3.3 million in R&D, which is a bit more than double, up 109% from the $1.6 million we spent on R&D in the full year of 2022. Our full-year G&A of $1.2 million was similar to the quarter, down almost 40% from the amount we spent in the year-ago period, again primarily because we had only minimal stock-based compensation expense as nearly all of the issued stock options were fully vested at that point.

2023 年全年，我們在研發上花費了 330 萬美元，比 2022 年全年的 160 萬美元研發支出增加了一倍多，成長了 109%。我們全年的一般及行政開支為 120 萬美元，與本季度相似，比去年同期的支出下降了近 40%，這主要因為我們的股票薪酬支出很少，因為幾乎所有發行的股票期權都在那時完全歸屬。

For the full-year net income, we lost $4.5 million, which is 27% more than we had lost in 2022, driven primarily by our higher R&D spend because of our clinical trial activities. As for our cash, we ended the year with $4.1 million in cash and cash equivalents, which is down from the $8.0 million that we had as of December 31, 2022. We believe that our current cash reserves are sufficient to fund all of our Phase 1 clinical trial.

全年淨收入方面，我們虧損 450 萬美元，比 2022 年的虧損增加了 27%，這主要是因為我們的臨床試驗活動增加了研發支出。至於我們的現金，截至今年年底，我們的現金和現金等價物為 410 萬美元，低於截至 2022 年 12 月 31 日的 800 萬美元。我們相信，我們目前的現金儲備足以資助我們所有第一階段的臨床試驗。

With that, I would like to turn the call back over to Garo.

說完這些，我想把電話轉回給 Garo。

Thank you very much, Bob, Andy, and Alex. In closing, I want to underscore the importance of having transitioned Protagenic into a clinical-stage biotech company. The novel mechanism of action of PT00114 which Bob and Andy described very nicely, coupled with the promising pharmacological and safety profile seen in preclinical studies, gives us a great deal of confidence in its potential therapeutic activity.

非常感謝鮑伯、安迪和亞歷克斯。最後，我想強調將 Protagenic 轉型為臨床階段生技公司的重要性。Bob 和 Andy 詳細描述了 PT00114 的新型作用機制，再加上臨床前研究中看到的有希望的藥理學和安全性特徵，讓我們對其潛在的治療活性充滿信心。

As we look ahead to 2024, our focus will be on efficiently executing the Phase 1 program and preparing for proof-of-concept efficacy studies in anxiety, depression, and other stress related conditions. As you heard from Bob and Andy, we are committed to bringing this potential breakthrough treatment to patients as expeditiously as possible.

展望 2024 年，我們的重點將放在有效執行第一階段計劃以及為焦慮、憂鬱和其他壓力相關疾病的概念驗證功效研究做準備。正如鮑伯和安迪所說，我們致力於盡快為患者帶來這種潛在的突破性治療方法。

This is an exciting time for our company as well as for patients. Of course, the mental health tragedy has been exacerbated with the onset of COVID and other conditions globally. On behalf of the entire leadership team, I want to thank all of you for your ongoing support of our mission. Together, I believe we can make a profound difference for patients and families affected by neuropsychiatric disorders.

對於我們公司和患者來說，這是一個令人興奮的時刻。當然，隨著新冠疫情和其他疫情在全球的爆發，心理健康悲劇進一步加劇。我謹代表整個領導團隊感謝大家對我們使命的持續支持。我相信，只要我們共同努力，就能為神經精神疾病患者及其家庭帶來巨大的改變。

We look forward to further updates as we progress our programs. Our agent is progressing in the clinic as planned and our plans for advancing this promising drug candidate remain absolutely unwavering as you heard.

隨著我們計劃的進展，我們期待進一步的更新。我們的藥物在臨床研究中正按計劃進展，正如您所聽到的，我們推進這一有前途的候選藥物的計劃絕對堅定不移。

Thanks again for your time and your participation in today's call. And I think now we are ready for any questions that you may have.

再次感謝您抽出時間參加今天的電話會議。我想現在我們已經準備好回答你們的任何問題了。

Thank you. (Operator Instructions)

謝謝。（操作員指示）

William Wood, B. Riley Securities.

威廉伍德 (William Wood)，B. Riley 證券。

Thank you so much for taking our questions and congratulations on a very nice quarter and year. We're just curious about -- two from us -- curious about the timeline for the readout of your SAD and MAD studies if we should be expecting those together, combined, or apart?

非常感謝您回答我們的問題，並祝賀您度過了一個非常愉快的季度和一年。我們只是好奇——我們兩個——好奇您的 SAD 和 MAD 研究讀數的時間表，我們應該期待它們一起、合併還是分開？

And then what are the next regulatory steps that you have for moving forward into your Phase 2 studies?

那麼，為了推進第二階段的研究，你們接下來要採取哪些監理措施呢？

So I'll ask Alex to address the first question and Andy, perhaps you or Bob can address the second.

因此，我會請亞歷克斯回答第一個問題，而安迪，也許你或鮑伯可以回答第二個問題。

Sure. So, William, good to hear from you. So your first question is the timeline for the readout of our SAD and MAD studies. So the SAD or single ascending dose study is in progress now. We plan to have enrollment in that study completed by the end of April.

當然。那麼，威廉，很高興收到你的來信。所以您的第一個問題是我們的 SAD 和 MAD 研究讀數的時間表。因此，SAD 或單次遞增劑量研究目前正在進行中。我們計劃在四月底完成這項研究的招生。

And as described in our last press release, we're planning to have a data readout on that within a couple of weeks of the completion of that session by mid-May.

正如我們上次新聞稿中所述，我們計劃在五月中旬會議結束後的幾週內公佈相關數據。

As for MAD, we intend to start enrolling essentially immediately as soon as SAD is complete and should have a data readout on that in early Q3. We had previously targeted July for that, for the readout for MAD. So I think that was the -- did I address all of your first question?

至於 MAD，我們打算在 SAD 完成後立即開始招募，並應在第三季初取得相關數據讀數。我們先前的目標是在 7 月公佈 MAD 的數據。所以我認為這是——我是否回答了您的所有第一個問題？

Yeah. Yeah, thank you.

是的。是的，謝謝。

Yeah, okay.

嗯，好的。

And who would like to handle the second one and additional steps we need under regulatory front?

誰願意處理第二個問題以及監管方面所需的額外步驟？

You're saying the additional steps to start the Phase 2, William, is that the nature --

威廉，你說啟動第二階段的額外步驟是--

I think the second question was, what are the additional milestones on the regulatory program as we advance PT00114? I think, Bob, perhaps something.

我認為第二個問題是，隨著 PT00114 的推進，監管計畫還有哪些里程碑？我想，鮑勃，也許有些事。

I can address that. We are in the process of finalizing our Phase 2 protocol and we'll have to submit that to the agency for approval. We're confident that we will have that because the compound is very safe and we've seen no safety signals so far.

我可以解決這個問題。我們正在敲定第二階段的協議，必須提交給該機構批准。我們有信心實現這一目標，因為這種化合物非常安全，而且到目前為止我們還沒有看到任何安全訊號。

I think we'll have been able to address an appropriate dose for those studies from some of the biomarker work that we are planning to conduct. And the format is very similar to studies that Dr. Fava has conducted with many other compounds in development for the treatment of anxiety and depression. He is really one of the world's leaders in the design of such studies.

我認為，我們能夠根據我們計劃進行的一些生物標記研究來確定這些研究的適當劑量。其形式與法瓦博士針對治療焦慮和憂鬱的許多其他化合物所進行的研究非常相似。他確實是此類研究設計領域的世界領導者之一。

You may want to say this is called a basket trial and has great acceptance with regulatory agencies.

你可能會說這被稱為籃子試驗，並且得到了監管機構的廣泛認可。

Yeah, that's a good point, Andy, because we do believe that the compound will have activity across a variety of neuropsychiatric disorders. And the plan is to enroll patients with examples of each of those and then track along the signals that we see for efficacy to enrich for those indications where we see the strongest signals at least initially.

是的，安迪，你的觀點很好，因為我們確實相信這種化合物可以治療多種神經精神疾病。該計劃是招募具有每種情況的患者，然後追蹤我們看到的療效訊號，以豐富那些我們至少在最初看到最強訊號的適應症。

Got it. I appreciate that. And then kind of building on that, just one last question. You're evaluating the healthy individuals in your ongoing SAD and then going into your MAD, should we be expecting any biomarker data from these initial trials, maybe highlighting the neuroprotective effects, understanding that they're primarily safety. But just curious what additional data possibly biomarker we may be able to expect.

知道了。我很感激。在此基礎上，我再問最後一個問題。您正在評估正在進行的 SAD 中的健康個體，然後進入 MAD，我們是否應該期待從這些初步試驗中獲得任何生物標記數據，也許會強調神經保護作用，了解它們主要是安全的。但我只是好奇我們可能能夠期待哪些額外的生物標記數據。

(multiple speakers) biomarker data, but one of the things one really needs to understand is when you're dealing with healthy volunteers and the way we actually treat healthy volunteers, we make sure that everything is calm. And so that there's no sort of setting up a stress or anxiety condition amongst those.

（多位發言者）生物標記數據，但人們真正需要了解的一件事是，當你與健康志工打交道時，我們實際對待健康志工的方式是確保一切都平靜。這樣就不會出現任何壓力或焦慮的情況。

But there are people who will come in and maybe a little stressed. And we are making sure that we're collect and sufficient amount of materials so we can actually gauge a responsive biomarker.

但有些人進來後可能會有點壓力。我們正在確保收集到足夠數量的材料，以便我們可以真正測量反應性生物標記。

But as a biomarker that we plan to announce, William, we do plan to announce cortisol levels when we announce the both the SAD and MAD results. In each case, we will have measured cortisol levels and tend to include those in the disclosure results.

但是，作為我們計劃公佈的生物標誌物，威廉，我們確實計劃在公佈 SAD 和 MAD 結果時公佈皮質醇水平。在每種情況下，我們都會測量皮質醇水平，並傾向於將其納入揭露結果。

Understood. And thank you for taking our questions. I appreciate it and congratulations again on a very nice quarter and year.

明白了。感謝您回答我們的問題。我對此表示感謝，並再次祝賀本季和今年取得了非常出色的成績。

Thanks, William.

謝謝，威廉。

Thank you.

謝謝。

(Operator Instructions) Okay, it looks like we have no further questions in queue. I'd like to turn the call back over to management for closing remarks.

（操作員指示）好的，看起來我們沒有其他問題了。我想將電話轉回給管理階層，請他們做最後發言。

Thank you very much, everybody, and thank you very much for your patience and participation through this journey. If you have additional questions, you can always feel free to call Alex and get to one of us. We welcome your engagement on a continuing basis. Thanks again.

非常感謝大家，也非常感謝你們在這趟旅程中的耐心與參與。如果您還有其他問題，可以隨時致電 Alex 並與我們聯繫。我們歡迎您繼續參與。再次感謝。

This concludes today's conference and you may disconnect your lines at this time. Thank you for your participation.

今天的會議到此結束，大家可以斷開連線了。感謝您的參與。