Acasti Pharma Inc (ACST) 2023 Q3 法說會逐字稿

Good day, and welcome to the Acasti Pharma Reports Third Quarter Fiscal Year 2020 Financial Results and Business Update Call. (Operator Instructions) Please note this event is being recorded.

美好的一天，歡迎來到 Acasti Pharma 報告 2020 財年第三季度財務業績和業務更新電話會議。 （操作員說明）請注意正在記錄此事件。

I would now like to turn the conference over to Robert Blum with Lytham Partners. Please go ahead.

我現在想將會議轉交給 Robert Blum 和 Lytham Partners。請繼續。

All right. Thank you very much, Jason. Welcome to Acasti Pharma's Third Quarter Fiscal 2023 Conference Call. On the call with us this afternoon is Jan D'Alvise, President and CEO; Brian Ford, Chief Financial Officer; Pierre Lemieux, Chief Operating and Scientific Officer; and Acasti Co-Founder and Prashant Kohli, Chief Commercial Officer.

好的。非常感謝你，傑森。歡迎來到 Acasti Pharma 的 2023 財年第三季度電話會議。今天下午與我們通電話的是總裁兼首席執行官 Jan D'Alvise；布賴恩·福特，首席財務官； Pierre Lemieux，首席運營官和科學官； Acasti 聯合創始人兼首席商務官 Prashant Kohli。

Following management's prepared remarks, there will be a Q&A session. Should any questions remain after the call, please contact me at 602-889-9700. I'd also like to remind everyone that statements on this conference call that are not statements of historical or current facts constitute forward-looking information within the meaning of Canadian securities laws and forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and the Securities and Exchange Act of 1934.

在管理層準備好的發言之後，將舉行問答環節。如果通話後仍有任何問題，請致電 602-889-9700 與我聯繫。我還想提醒大家，本次電話會議中的非歷史或當前事實陳述構成加拿大證券法意義上的前瞻性信息和美國私人證券訴訟改革意義上的前瞻性陳述1995 年法案和 1934 年證券交易法。

Such forward-looking statements involve known and unknown risks and uncertainties that could cause the actual results to be materially different from those expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, listeners are urged to consider statements labeled with terms such as belief, expects, intends, anticipates, potential, should, may, will, plans, continue, targeted or other similar expressions to be uncertain and forward-looking. Listeners are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this conference call.

此類前瞻性陳述涉及已知和未知的風險和不確定性，可能導致實際結果與此類前瞻性陳述明示或暗示的結果存在重大差異。除了明確描述此類風險和不確定性的陳述外，還敦促聽眾考慮標有諸如信念、期望、打算、預期、潛在、應該、可能、將、計劃、繼續、目標或其他類似表達方式的陳述不確定性和前瞻性。告誡聽眾不要過分依賴這些前瞻性陳述，這些陳述僅在本次電話會議之日發表。

Forward-looking statements during this conference call may include, but are not limited to, the success and timing of regulatory submissions of Acasti's planned preclinical and clinical trials, regulatory requirements or developments and the outcome of meetings with the FDA, changes to clinical trial designs and regulatory pathways, legislative, regulatory, political and economic developments and actual costs associated with Acasti's preclinical and clinical trials as compared to management's current expectations.

本次電話會議期間的前瞻性陳述可能包括但不限於 Acasti 計劃的臨床前和臨床試驗的監管提交的成功和時間安排、監管要求或發展以及與 FDA 會議的結果、臨床試驗設計的變化與管理層目前的預期相比，與 Acasti 的臨床前和臨床試驗相關的監管途徑、立法、監管、政治和經濟發展以及實際成本。

The forward-looking statements made during this conference call are expressly qualified in their entirety by this cautionary statement, the cautionary note regarding forward-looking information section and the risk factors contained in documents that have been filed and are filed by Acasti from time to time with the Securities and Exchange Commission and Canadian securities regulators, which are available on EDGAR at www.sec.gov on Sedar at sedar.com and on the Investors section of the Acasti website at www.acasti.com.

本次電話會議期間作出的前瞻性陳述在本警示聲明、關於前瞻性信息部分的警示說明以及 Acasti 已提交和不時提交的文件中包含的風險因素中明確限定與證券交易委員會和加拿大證券監管機構的合作，可在 EDGAR 的 www.sec.gov、Sedar 的 sedar.com 和 Acasti 網站 www.acasti.com 的投資者部分獲取。

In addition, any forward-looking statements represent Acasti's views as of today and should not be relied upon as representing our views of any subsequent date. Acasti undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date in which they were made except as required by applicable securities law.

此外，任何前瞻性陳述均代表 Acasti 截至今天的觀點，不應被視為代表我們對任何後續日期的觀點。除適用證券法要求外，Acasti 不承擔更新此類聲明以反映在聲明作出之日之後發生的事件或存在的情況的義務。

I'd now like to turn the call over to Jan D'Alvise, President and CEO of Acasti. Jan, please proceed.

我現在想把電話轉給 Acasti 總裁兼首席執行官 Jan D'Alvise。簡，請繼續。

Thank you, Robert, and thank you to everyone joining the call today. We're very excited to update you on the significant progress made to advance our 3 clinical programs over the last few months. Let me start with a high-level overview and then I'll provide more details.

謝謝羅伯特，也感謝今天加入電話會議的所有人。我們很高興向您介紹過去幾個月在推進我們的 3 個臨床項目方面取得的重大進展。讓我從高級概述開始，然後我將提供更多詳細信息。

First, in late December 2022, we announced successful results following the completion of 2 pharmacokinetic or PK trials in human volunteers for both GTX-101 and 102. In both cases, the top line results met all primary outcome measures, allowing us to advance both programs to the next stage of clinical development in 2023. I'll expand more on each of these programs in a moment.

首先，在 2022 年 12 月下旬，我們在 GTX-101 和 102 的人類誌願者中完成了 2 項藥代動力學或藥代動力學試驗後宣布了成功的結果。在這兩種情況下，頂線結果都符合所有主要結果指標，使我們能夠推進兩者計劃到 2023 年臨床開發的下一階段。稍後我將詳細介紹這些計劃中的每一個。

Further, with GTX-104, we submitted a letter to the FDA to request a Type C meeting to review and discuss the results of the PK bridging study that was reported out last May as well as our proposed design for the Phase III safety study. We anticipate receiving the FDA's clarifying guidance before the end of calendar Q1. We expect that favorable guidance will confirm our 505(b)(2) regulatory strategy and will allow us to finalize the study protocol paving the way for the initiation of our Phase III safety study in patients with subarachnoid hemorrhage caused by a ruptured aneurysm or ASH.

此外，對於 GTX-104，我們向 FDA 提交了一封信，要求召開 C 類會議，以審查和討論去年 5 月報告的 PK 橋接研究的結果以及我們為 III 期安全研究提出的設計。我們預計在第一季度末之前收到 FDA 的澄清指南。我們希望有利的指導將確認我們的 505(b)(2) 監管策略，並使我們能夠最終確定研究方案，為我們在因動脈瘤破裂或 ASH 引起的蛛網膜下腔出血患者中開展 III 期安全性研究鋪平道路.

And very importantly, we finished the third fiscal quarter with $31.3 million in cash, cash equivalents and short-term investments. We continue to believe that based on current projections, we have sufficient capital to fund operations into calendar Q2 of 2024, allowing for the advancement of GTX 104 well into Phase III and advancing GTX-102 and 101 to key value inflection points. So at a high level, we ended the quarter in a very strong fashion, and we expect calendar 2023 to be even more exciting with 2 of our drug candidates ready to enter Phase III.

非常重要的是，我們以 3130 萬美元的現金、現金等價物和短期投資結束了第三財季。我們仍然相信，根據目前的預測，我們有足夠的資金為 2024 年第二季度的運營提供資金，從而使 GTX 104 順利推進到第三階段，並將 GTX-102 和 101 推進到關鍵值拐點。因此，在高水平上，我們以非常強勁的方式結束了本季度，我們預計 2023 年日曆會更加令人興奮，因為我們的 2 種候選藥物已準備好進入 III 期。

With that brief summary of the quarter, let me expand on the positive results that we received on our 2 PK studies as announced in December, and I'll also provide a brief reminder of the market opportunity that each of these drug candidates represent. I'll start with GTX-101, our topical spray form of bupivacaine that we're developing to treat patients with postherpetic neuralgia or PHN.

通過本季度的簡要總結，讓我詳細介紹我們在 12 月宣布的 2 個 PK 研究中收到的積極結果，我還將簡要提醒一下這些候選藥物中的每一個所代表的市場機會。我將從 GTX-101 開始，這是我們正在開發的用於治療帶狀皰疹後遺神經痛或 PHN 患者的布比卡因局部噴霧劑。

On December 22, we announced that the top line results for our single-dose PK study for GTX-101 met all its primary outcome measures for the study. This study was designed to evaluate the relative bioavailability of GTX-101 compared to a subcutaneous injection of the bupivacaine which is the reference listed drug in the United States for regulatory purposes.

12 月 22 日，我們宣布 GTX-101 單劑量 PK 研究的頂級結果符合該研究的所有主要結果指標。本研究旨在評估 GTX-101 與皮下注射布比卡因相比的相對生物利用度，布比卡因是美國用於監管目的的參考上市藥物。

This PK study was the next step in the proposed 505(b)(2) regulatory pathway for GTX-101 and the results provide us with important information on the dose and dosing frequency in humans for future planned clinical studies.

這項 PK 研究是擬議的 GTX-101 505(b)(2) 監管途徑的下一步，結果為我們提供了有關人類劑量和給藥頻率的重要信息，以供未來計劃的臨床研究使用。

As a reminder, GTX-101 is a unique and patented formulation of bupivacaine hydrochloride that incorporates a novel bioadhesive film-forming polymer and is administered via a topical spray. As I mentioned, GTX-101 is being developed to relieve the severe pain associated with PHN, the persistent and often debilitating neuropathic pain caused by nerve damage from the Varicella zoster virus , the virus that causes shingles and chickenpox.

提醒一下，GTX-101 是一種獨特的專利鹽酸布比卡因配方，它結合了一種新型生物粘附成膜聚合物，並通過局部噴霧劑給藥。正如我提到的，正在開發 GTX-101 以緩解與 PHN 相關的劇烈疼痛，PHN 是由水痘帶狀皰疹病毒引起的神經損傷引起的持續且經常使人衰弱的神經性疼痛，這種病毒會導致帶狀皰疹和水痘。

PHN pain may persist for months or even years. And based on our primary market research, there are still significant unmet medical needs for this indication. The single dose PK study enrolled 48 healthy adult subjects with 24 males and 24 females having a mean age of 36 years, and they were randomized into 4 separate cohorts with 12 subjects in each cohort. Subjects in cohorts 1, 2 and 3 received 50, 100 or 200 milligrams of GTX-101, respectively, in adjacent and overlapping sprays on the lower back.

PHN 疼痛可能會持續數月甚至數年。根據我們的主要市場研究，該適應症仍有大量未滿足的醫療需求。單劑量 PK 研究招募了 48 名健康成年受試者，其中 24 名男性和 24 名女性平均年齡為 36 歲，他們被隨機分配到 4 個獨立的隊列中，每個隊列中有 12 名受試者。第 1、2 和 3 組中的受試者分別接受了 50、100 或 200 毫克的 GTX-101，在下背部相鄰和重疊的噴霧劑中。

Subjects in Cohort 4 received a single 10-milligram subcutaneous injection of the active bupivacaine comparator. The primary objective of this PK study was to assess the pharmacokinetics of 3 different dose levels of GTX-101 at 50,100 and 200 milligrams. Each dose of GTX-101 was administered to a separate cohort of 12 subjects as a single-dose topical application in a metered spray.

隊列 4 中的受試者接受單次 10 毫克活性布比卡因比較劑皮下注射。本 PK 研究的主要目的是評估 50,100 和 200 毫克的 3 種不同劑量水平的 GTX-101 的藥代動力學。將每劑 GTX-101 作為單劑量局部應用以計量噴霧形式施用於 12 名受試者的單獨隊列。

For clarity, 50 milligrams was delivered as 5 sprays, 100 milligrams to 10 sprays and 200 milligrams of 20 sprays. These patients were not administered one on top of the other, but rather adjacently to cover the entire targeted area. An additional 12 subjects in Cohort 4 received a single 10-milligram subcutaneous injection of the active comparator.

為清楚起見，50 毫克作為 5 次噴霧交付，100 毫克至 10 次噴霧和 200 毫克作為 20 次噴霧交付。這些患者不是一個接一個地接受治療，而是相鄰接受治療以覆蓋整個目標區域。隊列 4 中的另外 12 名受試者接受了活性比較劑的單次 10 毫克皮下注射。

A secondary objective of this study was to compare the bioavailability of these 2 very different modes of administration. The data from this study provides us now with key information that helps us to further characterize the PK parameters and the safety and tolerability of GTX-101 and will support additional future clinical development. We expect that the full clinical study report will be received from the CRO in the first half of calendar 2023, and we intend to publish this data.

本研究的第二個目的是比較這兩種截然不同的給藥方式的生物利用度。這項研究的數據現在為我們提供了關鍵信息，可幫助我們進一步表徵 GTX-101 的 PK 參數以及安全性和耐受性，並將支持更多的未來臨床開發。我們預計將在 2023 年上半年從 CRO 收到完整的臨床研究報告，我們打算發布這些數據。

We plan to follow the successful PK study with a multiple ascending dose study results from both of these Phase I clinical studies once completed, will be required before we can initiate our Phase II program in PH1 patients.

我們計劃在成功的 PK 研究之後進行這兩項 I 期臨床研究的多次遞增劑量研究結果，一旦完成，我們將需要在 PH1 患者中啟動我們的 II 期計劃。

As background, the current treatment of PHN most often starts with oral gabapentin prescribed as a first-line therapy. And when that fails, as it often does due to poor efficacy and unpleasant side effects, lidocaine patches are typically prescribed as a second-line therapy. According to our recent market research with more than 250 physicians who regularly treat these patients, up to 40% of patients do not experience satisfactory pain relief from the patch. And these refractory patients may end up being prescribed opioids to address their persistent pain.

作為背景，目前 PHN 的治療通常以口服加巴噴丁作為一線治療開始。當這種方法失敗時，通常會因療效不佳和令人不快的副作用而失敗，利多卡因貼劑通常被開具處方作為二線療法。根據我們最近對 250 多位定期治療這些患者的醫生進行的市場調查，多達 40% 的患者無法從貼片中獲得令人滿意的疼痛緩解。這些難治性患者最終可能會被開阿片類藥物來解決他們的持續性疼痛。

Gabapentin and opioid abuse has continued to proliferate and lidocaine patches are suboptimal for many reasons. The Lidocaine patch can only be worn for 12 hours at a time. They're difficult to use as they fall off and can cause skin sensitivity and irrigation, especially in older individuals. And depending on their placement, they can be inconvenient, uncomfortable and unattractive. Prescription lidocaine patches are currently only approved for PHN, and the market is made up of both branded and generic offerings. You can certainly see the many issues with the current treatment options that we hope GTX-101 will address.

加巴噴丁和阿片類藥物的濫用繼續激增，利多卡因貼劑由於多種原因不是最佳選擇。利多卡因貼片一次只能佩戴 12 小時。它們很難使用，因為它們會脫落並且會導致皮膚敏感和沖洗，尤其是在老年人中。根據它們的位置，它們可能會帶來不便、不舒服和缺乏吸引力。處方利多卡因貼劑目前僅獲准用於 PHN，市場由品牌藥和仿製藥組成。您當然可以看到我們希望 GTX-101 能夠解決的當前治療方案的許多問題。

It's important to note that the potential benefits of GTX-101 could include faster onset of action and a longer duration of pain relief as compared to the lidocaine patch. GTX-01 can be conveniently sprayed on the skin wherever the pain is located. And based on the PK profile of bupivacaine, we believe that GTX-101 may only need to be applied to the affected area once a day or possibly even less frequently to get 24/7 pain relief, although this dosing schedule will be confirmed in additional clinical studies.

重要的是要注意，與利多卡因貼片相比，GTX-101 的潛在好處可能包括起效更快和疼痛緩解持續時間更長。 GTX-01 可以方便地噴在疼痛部位的皮膚上。根據布比卡因的 PK 曲線，我們認為 GTX-101 可能只需要每天一次或可能更少地應用於受影響的區域，以獲得 24/7 的疼痛緩解，儘管這個給藥時間表將在額外的確認臨床研究。

Based on this product profile and assuming a successful development program, we believe GTX-101 has its potential to be a game changer as a non-opioid alternative to the lidocaine patch for PHN patients who suffer from this debilitating pain.

基於此產品概況並假設一個成功的開發計劃，我們相信 GTX-101 有潛力成為遊戲規則的改變者，作為患有這種衰弱性疼痛的 PHN 患者的利多卡因貼片的非阿片類藥物替代品。

In terms of market size, it's estimated that PHN affects approximately 130,000 patients per year in the United States. And according to the third-party market research report commissioned by Acasti, the total addressable market for GTX-101 could be as large as $2.5 billion, consisting of approximately $200 million for PHN pay and $2.3 billion for non-PHN pay. So this certainly represents a large addressable market opportunity for Acasti.

就市場規模而言，據估計 PHN 在美國每年影響約 130,000 名患者。根據 Acasti 委託的第三方市場研究報告，GTX-101 的總潛在市場可能高達 25 億美元，其中約 2 億美元用於 PHN 支付，23 億美元用於非 PHN 支付。因此，這無疑代表了 Acasti 的巨大潛在市場機會。

Now I'd like to transition to GTX-102. And on December 28 and only a week after we reported our positive clinical study results for GTX-101, we announced that the top line results of our GTX-102-001 PK bridging study met all primary outcome measures and represented an important milestone in the advancement of this program.

現在我想過渡到 GTX-102。在 12 月 28 日，也就是我們報告 GTX-101 陽性臨床研究結果僅一周後，我們宣布 GTX-102-001 PK 橋接研究的頂級結果符合所有主要結果指標，代表了該領域的一個重要里程碑本方案的推進。

The PK bridging study was a Phase I randomized, open-label crossover study in healthy adult subjects designed to evaluate the comparative bioavailability, pharmacokinetics and safety of GTX-102 administered as an oral spray compared to intramuscular betamethasone, which is expected to be the reference product for regulatory bridging purposes as well as to an oral solution of betamethasone, which is available in Europe but not in the United States. A total of 48 healthy adult subjects comprised of 27 males and 21 females were enrolled in a single center, 5 treatment, 8 sequence 2-period crossover study.

PK 橋接研究是一項針對健康成人受試者的 I 期隨機、開放標籤交叉研究，旨在評估 GTX-102 作為口腔噴霧劑與肌肉注射倍他米松相比的生物利用度、藥代動力學和安全性，預計將成為參考用於監管橋接目的的產品以及倍他米鬆口服溶液，後者在歐洲有售，但在美國沒有。共有 48 名健康成年受試者（包括 27 名男性和 21 名女性）被納入單一中心、5 項治療、8 個序列的 2 期交叉研究。

Our new and patented formulation of betamethasone is intended to improve the neurological symptoms of Ataxia Telangiectasia, or AT, in a pediatric population for which there are currently no FDA-approved therapies. GTX-102 can be sprayed conveniently over the ton of AT patients who often have difficulty swallowing.

我們新的專利倍他米松配方旨在改善目前尚無 FDA 批准療法的兒科人群共濟失調性毛細血管擴張症或 AT 的神經系統症狀。 GTX-102 可以方便地噴灑在大量吞嚥困難的 AT 患者身上。

As a reminder, the betamethasone oral solution that we're comparing to GTX-102 was shown to reduce neurological symptoms in children with AT and a multicenter, double-blind, randomized, placebo-controlled crossover trial conducted in Italy by Dr. Zanolli, and this study was published in 2012.

提醒一下，我們正在與 GTX-102 進行比較的倍他米鬆口服溶液被證明可以減少患有 AT 的兒童的神經系統症狀，並且 Zanolli 博士在意大利進行了一項多中心、雙盲、隨機、安慰劑對照的交叉試驗，這項研究發表於 2012 年。

As I mentioned, our PK bridging study met all primary outcome measures, providing us with confidence that the expected final development step for GTX-102 will now be to conduct a Phase III safety and efficacy trial in AT patients using a treatment regimen in a dosing range comparable to the one already shown to be effective in doctors Zanolli study.

正如我所提到的，我們的 PK 橋接研究符合所有主要結果指標，使我們有信心 GTX-102 的預期最終開發步驟現在將是在 AT 患者中使用治療方案進行 III 期安全性和有效性試驗範圍與 Zanolli 醫生研究中已經證明有效的範圍相當。

As background, I'll remind you that AT is a progressive genetic neurodegenerative disorder that primarily affects young children, causing severe disability, impairment of the immune system and an increasing susceptibility to infections and cancers. The hallmark symptoms of AT are [sellable], ataxia and other motor dysfunction as well as dilated blood vessels or telangiectasia that occur in the sclera of the eyes and on the skin.

作為背景，我要提醒您，AT 是一種進行性遺傳性神經退行性疾病，主要影響幼兒，導致嚴重殘疾、免疫系統受損以及感染和癌症的易感性增加。 AT 的標誌性症狀是 [sellable]、共濟失調和其他運動功能障礙，以及出現在眼睛鞏膜和皮膚上的血管擴張或毛細血管擴張。

Children begin to experience balance and coordination problems when they begin to walk at a toddler age and ultimately, they become wheelchair bound in their second decade of life. In preadolescents around 5 to 8 years of age, patients experience ocular motor apraxia. This is difficult to moving their eyes in a desired direction. And they also experienced a weakness in the muscles of the space used for speech, causing slowed or slurred speech as well as dysphagia or difficulty swallowing. They often develop compromised immune systems and are at an increased risk of developing respiratory tract infections in cancers, typically lymphoma and leukemia.

孩子們在蹣跚學步的年齡開始走路時就開始出現平衡和協調問題，最終，他們在生命的第二個十年成為坐輪椅的人。在 5 至 8 歲左右的青春期前，患者會出現眼球運動失用症。這很難將他們的眼睛移向所需的方向。他們還經歷了用於說話的空間肌肉無力，導致說話速度減慢或含糊不清以及吞嚥困難或吞嚥困難。他們的免疫系統通常會受損，並且患上呼吸道感染癌症（通常是淋巴瘤和白血病）的風險會增加。

Patients typically die in their second decade of life from complications of lung disease or cancer. Unfortunately, there's no known treatment to slow the disease progression of AT and treatments that are used are strictly aimed at symptoms or conditions secondary to the disease.

患者通常在生命的第二個十年死於肺部疾病或癌症的並發症。不幸的是，沒有已知的治療方法可以減緩 AT 的疾病進展，所使用的治療方法嚴格針對疾病的繼發症狀或病症。

A third-party market research study that we commissioned found ATF approximately 4,300 patients per year in the United States and has a potential addressable market of about $150 million based on the number of treatable patients.

我們委託進行的第三方市場研究發現，ATF 在美國每年約有 4,300 名患者，根據可治療患者的數量，潛在潛在市場約為 1.5 億美元。

[The same] muscular dystrophy, or DMD, is another rare inherited and progressive muscular disorder that typically affects boys. And like AT, it is often diagnosed at a young age. Emflaza is the first and only FDA-approved corticosteroid for treating boys with DMD over the age of 2. Like GTX-102, the dosing of Emflaza is determined for this pediatric population based on their weight.

[相同] 肌營養不良症或 DMD 是另一種罕見的遺傳性和進行性肌肉疾病，通常會影響男孩。和 AT 一樣，它通常在年輕時就被診斷出來。 Emflaza 是 FDA 批准的第一個也是唯一一個用於治療 2 歲以上 DMD 男孩的皮質類固醇。與 GTX-102 一樣，Emflaza 的劑量是根據他們的體重確定的。

Emflaza, which is sold by PTC Pharmaceuticals was launched back in 2017, and it's reached more than $200 million in sales last year. Given the many similarities with GTX-102, we believe that Emflaza could serve as an excellent analog for successful commercialization of our drug.

由 PTC Pharmaceuticals 銷售的 Emflaza 於 2017 年推出，去年銷售額已超過 2 億美元。鑑於與 GTX-102 的許多相似之處，我們相信 Emflaza 可以作為我們藥物成功商業化的優秀類似物。

In terms of next steps following the receipt of the full PK data study data set from our CRO, which is expected sometime in the first half of calendar 2023, we plan to request a Type B meeting with the FDA to confirm our proposed Phase III study design and the 505(b)(2) bridging strategy with the listed intramuscular form of the drug. If all proceeds as planned, the study start-up activities for Phase III safety and efficacy study are expected to be initiated by the end of calendar 2023. If the Phase III program meets the primary endpoint and NDA filing for GTX-102 under Section 505(b)(2) is expected to follow.

關於從我們的 CRO 收到完整的 PK 數據研究數據集後的後續步驟，預計在 2023 年上半年的某個時候，我們計劃要求與 FDA 舉行 B 類會議，以確認我們提議的 III 期研究設計和 505(b)(2) 橋接策略與所列藥物的肌肉注射形式。如果一切按計劃進行，III 期安全性和有效性研究的研究啟動活動預計將在 2023 日曆年底啟動。如果 III 期計劃符合第 505 條下 GTX-102 的主要終點和 NDA 備案(b)(2) 預計會跟進。

Transitioning now to GTX-104, our lead development program. As previously discussed, we submitted a Type C meeting package to the FDA back in November. That package included the data from our PK bridging study as well as our proposed design for our Phase III safety study. We anticipate receiving the FDA's clarifying guidance before the end of calendar Q1. This should allow us to benefit from the FDA's buy-in and should allow us to begin recruiting clinical sites and initiate the Phase III safety study as planned. We've already selected our CRO and clinical trial site selection is currently underway.

現在過渡到我們的主導開發計劃 GTX-104。如前所述，我們在 11 月份向 FDA 提交了 C 類會議文件。該軟件包包括來自我們 PK 橋接研究的數據以及我們為我們的 III 期安全性研究提出的設計。我們預計在第一季度末之前收到 FDA 的澄清指南。這應該使我們能夠從 FDA 的支持中受益，並且應該允許我們開始招募臨床站點並按計劃啟動 III 期安全性研究。我們已經選擇了我們的 CRO，目前正在進行臨床試驗地點選擇。

For those of you who may not already be familiar with our lead drug candidate, GTX-104 is a novel patented formulation of nimodipine for IV infusion designed specifically for patients with aneurysmal subarachnoid hemorrhage or ASH. Which is a condition caused by bleeding on the brain due to a ruptured aneurysm.

對於那些可能還不熟悉我們的主要候選藥物的人來說，GTX-104 是一種用於靜脈輸注的尼莫地平的新型專利製劑，專為動脈瘤性蛛網膜下腔出血或 ASH 患者設計。這是由於動脈瘤破裂導致大腦出血引起的病症。

ASH presents a life-threatening emergency for the patient and our new proprietary IV drug formulation addresses the vital need in the critical care market that's seen little innovation over the last 30 years. The condition of ASH patients is so critical that 10% to 15% of them die before ever reaching the hospital and about 1/3 ultimately do not survive. Another 1/3 of these patients require dependent care for the rest of their lives.

ASH 對患者來說是一種危及生命的緊急情況，而我們新的專有 IV 藥物配方可滿足重症監護市場的重要需求，該市場在過去 30 年裡幾乎沒有創新。 ASH 患者的病情非常危急，其中 10% 到 15% 的患者在到達醫院之前就已經死亡，大約 1/3 的患者最終無法存活。這些患者中還有 1/3 的餘生需要依賴他人的照顧。

As a reminder, we completed a Phase I PK bridging study in May of 2022, which successfully met all of its endpoints. The primary objective of the study was to evaluate the relative bioavailability of our GTX-104 administered as a continuous IV infusion compared to oral nimodipine capsules in healthy adult nail and female subjects while the secondary objective was to assess its safety and tolerability.

提醒一下，我們在 2022 年 5 月完成了 I 期 PK 橋接研究，成功達到了所有終點。該研究的主要目的是評估我們的 GTX-104 作為連續 IV 輸注給藥與口服尼莫地平膠囊相比在健康成人指甲和女性受試者中的相對生物利用度，而次要目的是評估其安全性和耐受性。

Importantly, the inter and interest subject variability was much lower for GTX-104 as compared with oral nimodipine. We believe that because of its better absorption profile and more consistent and predictable blood levels, DTX-104 may provide physicians with a more reliable and effective treatment for patients with ASH. This could be a major advantage as GTX-104 could help to reduce the incidence of hypotensive events and vasospasm, which require immediate and costly intervention, such as balloon angioplasty or the use of intra-arterial vasopressors, which can lead to worse outcomes for the patients.

重要的是，與口服尼莫地平相比，GTX-104 的受試者間和興趣受試者變異性要低得多。我們相信，由於其更好的吸收特性和更一致和可預測的血液水平，DTX-104 可以為醫生提供更可靠和有效的治療 ASH 患者的方法。這可能是一個主要優勢，因為 GTX-104 可以幫助減少低血壓事件和血管痙攣的發生率，這需要立即進行昂貴的干預，例如球囊血管成形術或使用動脈內血管加壓藥，這可能導致更糟糕的結果患者。

As I mentioned, while we wait for the guidance from the FDA on our proposed Phase III study design, we continue to plan and prepare for the initiation of the study. We have engaged a CRO to manage the study for us and we are qualifying and recruiting sites now to enroll patients. We expect the study to take about 18 months to complete once the first patient is enrolled. And if the trial is successful, it is expected to be the final clinical step required to seek market approval under the 505(b)(2) regulatory pathway. We're eager to hear back from the FDA, and we look forward to providing a market update once we receive our guidance.

正如我所提到的，在我們等待 FDA 就我們提議的 III 期研究設計提供指導的同時，我們繼續計劃和準備研究的啟動。我們已聘請 CRO 為我們管理研究，我們現在正在篩选和招募站點以招募患者。我們預計，一旦第一位患者入組，該研究將需要大約 18 個月的時間才能完成。如果試驗成功，預計這將是根據 505(b)(2) 監管途徑尋求市場批准所需的最後臨床步驟。我們渴望收到 FDA 的回复，我們期待在收到我們的指導後提供市場更新。

Before I turn it over to Brian to review our Q3 financials, I think it's important to mention that the strategy that we're undertaking to leverage across these unique drug delivery capabilities by reformulating and repurposing marketed drugs for new orphan indications where significant unmet medical need exists, is advancing nicely according to our plans. The well-understood efficacy and safety profiles of the currently marketed forms of these drugs provide the opportunity for us to utilize the FDA's Section 505(b)(2) regulatory pathway for the expedited development of our reformulated drug candidates, and therefore, may provide -- potentially provide a shorter, less risky and less costly path to regulatory approval.

在我將其交給 Brian 審查我們第三季度的財務狀況之前，我認為重要的是要提到我們正在採取的戰略，通過重新制定和重新利用已上市的藥物，用於新的孤兒適應症，這些藥物的顯著未滿足的醫療需求存在，正在按照我們的計劃順利推進。這些藥物目前上市形式的眾所周知的療效和安全性概況為我們提供了利用 FDA 第 505(b)(2) 條監管途徑加速開發我們重新配製的候選藥物的機會，因此，可以提供——可能提供更短、風險更小、成本更低的監管審批途徑。

And as I've mentioned before, all 3 of our drug candidates have already received orphan drug designation from the FDA and have the potential to be considered for fast-track review and approval. Orphan drug designation provides for 7 years of marketing exclusivity in the United States post launch, provided certain conditions are met and 10 years in Europe. These rare diseases also typically involve clinical trials with fewer patients and provide market opportunities that often require a much smaller, more targeted commercial infrastructure.

正如我之前提到的，我們的所有 3 種候選藥物都已獲得 FDA 的孤兒藥指定，並有可能被考慮進行快速審查和批准。孤兒藥指定在美國上市後提供 7 年的市場獨占權，前提是滿足某些條件，在歐洲為 10 年。這些罕見疾病通常還涉及較少患者的臨床試驗，並提供通常需要更小、更有針對性的商業基礎設施的市場機會。

It's important to point out that the orphan diseases that Acasti has targeted for drug development are well understood, although these patient populations may remain poorly served by available therapies or for example, in the case of our GTX-102 for children with AT, approved drug therapies do not yet exist. Our aim is to effectively treat the debilitating symptoms that results from these underlying diseases with the ultimate goal of improving quality of life and outcomes for these patients and their families.

重要的是要指出 Acasti 針對藥物開發的孤兒疾病是眾所周知的，儘管這些患者群體可能仍然無法得到可用療法的服務，或者例如，在我們用於 AT 兒童的 GTX-102 的情況下，批准的藥物療法尚不存在。我們的目標是有效治療由這些潛在疾病引起的衰弱症狀，最終目標是改善這些患者及其家人的生活質量和結果。

We believe that leveraging the Section 505(b)(2) regulatory pathway for the development of our reformulated versions of these drugs provides us with highly attractive opportunities in orphan disease indications with little or no current competition.

我們相信，利用第 505(b)(2) 條監管途徑來開發我們重新配製的這些藥物版本，為我們在孤兒病適應症方面提供了極具吸引力的機會，目前競爭很少或沒有。

With that, I'd like to turn the call over now to Brian Ford, our CFO, to review our financial results. I'll then quickly wrap things up, and we can then open the call up for questions. Brian?

有了這個，我想現在把電話轉給我們的首席財務官布賴恩福特，以審查我們的財務業績。然後我會快速總結一下，然後我們可以打開電話提問。布萊恩？

Thanks, Jan. Please note that unless otherwise indicated, all financial numbers that we discuss are nominated in U.S. dollars and the financials are reported to conforming to U.S. GAAP guidelines. We should also note that we are a clinical stage company. Thus, we do not yet generate revenues or have any cost of goods expenses.

謝謝，Jan。請注意，除非另有說明，否則我們討論的所有財務數字均以美元指定，並且財務報告符合美國公認會計原則準則。我們還應該注意到，我們是一家臨床階段公司。因此，我們尚未產生收入或有任何商品成本費用。

Research and development expenses, net of government assistance for the 3 months ended December 31, 2022, totaled $2.5 million compared to $2.2 million for the 3 months ended December 31, 2021. Our research and development during the quarter ended December 31, 2022, was focused primarily on advancing our clinical development programs for GTX-104,102 and 101, the drug candidates.

截至 2022 年 12 月 31 日止三個月，扣除政府援助後的研發費用總計 250 萬美元，而截至 2021 年 12 月 31 日止三個月，研發費用為 220 萬美元。我們在截至 2022 年 12 月 31 日止季度的研發費用為主要專注於推進我們的候選藥物 GTX-104,102 和 101 的臨床開發計劃。

General and administrative expenses for the 3 months ended December 31, 2022, were $1.6 million compared to $1.8 million for the 3 months ended December 31, 2021. This decrease was the result of decreased legal, tax, accounting and other professional fees that had been incurred in connection with the Grace acquisition. The decrease in professional fees was partly offset by an increase in salaries and benefits due to the reinstated accruals for our employee incentive bonus programs.

截至 2022 年 12 月 31 日止三個月的一般和行政費用為 160 萬美元，而截至 2021 年 12 月 31 日止三個月為 180 萬美元。減少的原因是法律、稅務、會計和其他專業費用減少因收購 Grace 而產生。由於我們的員工激勵獎金計劃恢復了應計費用，因此專業費用的減少部分被工資和福利的增加所抵消。

Loss from operating activities for the 3 months ended December 31, 2022, and was $4.2 million compared to a loss of $4.5 million for the 3 months ended December 31, 2021. For the 3 months ended September 30, 2021, a financial gain of $0.7 million resulted mostly from the decrease in the fair value of the derivative warrant liabilities.

截至 2022 年 12 月 31 日止三個月的經營活動虧損為 420 萬美元，而截至 2021 年 12 月 31 日止三個月的經營活動虧損為 450 萬美元。截至 2021 年 9 月 30 日止三個月，財務收益為 0.7 美元億元主要是由於衍生權證負債的公允價值下降。

Net loss and total comprehensive loss for the 3 months ended December 31, 2022, was $3.9 million or a loss of $0.09 per share, which was pretty much identical to the net loss of $3.8 million or a loss of $0.09 per share for the 3 months ended December 31, 2021.

截至 2022 年 12 月 31 日止三個月的淨虧損和綜合虧損總額為 390 萬美元或每股虧損 0.09 美元，與這三個月的淨虧損 380 萬美元或每股虧損 0.09 美元幾乎相同截至 2021 年 12 月 31 日。

Cash, cash equivalents and short-term investments totaled $31.3 million as of December 31, 2022, compared to $34.9 million in cash, cash equivalents and short-term investments as at September 30, 2022.

截至 2022 年 12 月 31 日，現金、現金等價物和短期投資總計 3130 萬美元，而截至 2022 年 9 月 30 日，現金、現金等價物和短期投資為 3490 萬美元。

As Jan mentioned, we continue to believe that we have sufficient capital to fund operations into calendar Q2 of 2022 for 2024, which would include the ability to fund our lead asset, GTX-104, well into Phase III and GTX-102 and 101 to additional important milestones.

正如 Jan 所提到的，我們仍然相信我們有足夠的資金來為 2022 年第二季度和 2024 年的運營提供資金，其中包括為我們的主要資產 GTX-104 提供資金進入 III 期和 GTX-102 和 101 的能力額外的重要里程碑。

With that, I'll now turn the call back over to Jan.

有了這個，我現在將電話轉回 Jan。

Thank you, Brian. So to quickly wrap things up, we ended calendar 2022 in a very strong fashion with the completion of 3 successful clinical trials, 2 that reported out in December alone. We look forward to receiving clarifying guidance from the FDA before the end of Q1 on the Phase III study design for our lead program GTX-104, which should pave the way for the initiation of our Phase III safety study later this year, with Phase III studies for both GTX-104 and GTX-102 expected to be initiated in calendar 2023, we believe this could be our most exciting year yet. And we look forward to keeping you all apprised of our progress towards our many milestones this year.

謝謝你，布萊恩。因此，為了快速總結，我們以非常強大的方式結束了 2022 日曆，完成了 3 項成功的臨床試驗，其中 2 項僅在 12 月就報告了。我們期待在第一季度末之前收到 FDA 關於我們的主導項目 GTX-104 的 III 期研究設計的明確指導，這將為今年晚些時候啟動我們的 III 期安全研究鋪平道路，第三階段GTX-104 和 GTX-102 的研究預計將於 2023 年啟動，我們相信這可能是我們迄今為止最激動人心的一年。我們期待讓大家了解我們今年在實現許多里程碑方面取得的進展。

So with that, I'll turn the call back over to the operator. Jason, can you open it up for questions for us?

因此，我將把電話轉回給接線員。傑森，你能打開它問我們問題嗎？

Yes. (Operator Instructions) Our first question comes from Leland Gershell from Oppenheimer.

是的。 （操作員說明）我們的第一個問題來自奧本海默的 Leland Gershell。

Thanks Jan, for the update. Just a question from me. As you get 102 into its next trial this year, wondering if you could share with us any view on enrollment time lines and potential timing for the top line data?

感謝 Jan 的更新。只是我的一個問題。當您今年進入 102 的下一次試驗時，想知道您是否可以與我們分享您對註冊時間線和頂級數據的潛在時間的任何看法？

Yes. Thanks, Leland. Well, as I mentioned, we are really now waiting on the final clinical trial report. We need to submit that to the FDA before we can start the Phase III. And we have always felt that it's a good idea to make sure that we get the FDA's input into the Phase III plans before we move forward. So we do plan to -- once we get our final clinical trial report submit a draft protocol to the FDA with our proposed study design and we really want the FDA's feedback on that.

是的。謝謝，利蘭。好吧，正如我提到的，我們現在真的在等待最終的臨床試驗報告。在我們開始 III 期之前，我們需要將其提交給 FDA。我們一直認為，在我們向前推進之前，確保我們將 FDA 的意見納入 III 期計劃是一個好主意。所以我們確實計劃——一旦我們得到最終的臨床試驗報告，就向 FDA 提交一份協議草案，其中包含我們提出的研究設計，我們真的希望 FDA 對此提供反饋。

And so what we're doing now is we're working with our key opinion leaders and our regulatory experts to really draft the design of the study. We're well into that. We're really looking to get a lot of really good input here over the next couple of months from our key opinion leaders. And then we'll plan to submit all of that. And I would expect, given the kind of time clock on this that the Type B meeting would be sometime this summer. And once we get their feedback, of course, we'll be planning the study in parallel. So we're, again, hoping that we can initiate startup activities certainly in the second half of this year.

因此，我們現在正在做的是與我們的主要意見領袖和監管專家合作，真正起草研究設計。我們對此很滿意。在接下來的幾個月裡，我們真的希望從我們的主要意見領袖那裡得到很多非常好的意見。然後我們將計劃提交所有這些。我預計，鑑於這方面的時間安排，B 類會議將在今年夏天的某個時間舉行。當然，一旦我們得到他們的反饋，我們就會同時計劃這項研究。因此，我們再次希望我們能夠在今年下半年啟動創業活動。

(Operator Instructions) our next question comes from Oren Livnat from H.C. Wainwright.

（操作員說明）我們的下一個問題來自 H.C. 的 Oren Livnat。溫賴特。

Congrats on the progress. I actually have a few. On 104, are you able to clarify if you already did have that Type C meeting with the FDA? And if so, I know we're waiting on the minutes, of course, but are you able or allowed to give us any sort of color there, if there's any surprises? Or as far as you could tell things going according to plan for just a strictly safety Phase III study? And I have a few follow-ups.

祝賀進步。我其實有幾個。關於 104，您能否澄清您是否已經與 FDA 進行了 C 類會議？如果是這樣，我知道我們當然在等待會議記錄，但是如果有任何驚喜，您是否能夠或允許給我們任何顏色？或者就您所知，一切都在按照嚴格安全的 III 期研究計劃進行？我有一些後續行動。

Yes, sure. Thanks, Oren. And so no, we are waiting on guidance from the FDA. We're asking them to clarify a number of things. So based on our positive results from our PK study, we've asked them to confirm whether we are eligible to use the 505(b)(2) regulatory pathway. We showed bioequivalence with the oral. So we believe that straightforward, but we want to get that confirmation from them. We also want them to confirm our proposed dosing regimen. We are recommending a 3.6 milligram bolus, delivered over 30 minutes, and that's followed by a continuous infusion.

是的，當然。謝謝，奧倫。所以不，我們正在等待 FDA 的指導。我們要求他們澄清一些事情。因此，根據 PK 研究的積極結果，我們要求他們確認我們是否有資格使用 505(b)(2) 監管途徑。我們顯示了與口服的生物等效性。所以我們認為這很簡單，但我們希望得到他們的確認。我們還希望他們確認我們提議的給藥方案。我們建議在 30 分鐘內推注 3.6 毫克，然後持續輸注。

Again, we're proposing a rate of 1.2 milligrams per hour. This was the dosing regimen that matched the Cmax on day 1 and the AUC at day 3 of the oral. So again, it's really important that we get the FDA's confirmation on that. and we do not have that yet. And we're also asking them to give us guidance on the number of patients. And again, based on previous discussions with the FDA, we are guesstimating or estimating that it'd be somewhere between 100 and 200 patients. But we want -- we need to get that confirmation from them, and we also want their feedback very importantly on how they want us to define a hypotensive event.

同樣，我們提議的速率為每小時 1.2 毫克。這是與口服第 1 天的 Cmax 和第 3 天的 AUC 相匹配的給藥方案。因此，再次強調，我們獲得 FDA 的確認非常重要。我們還沒有。我們還要求他們就患者數量向我們提供指導。同樣，根據之前與 FDA 的討論，我們正在猜測或估計它會在 100 到 200 名患者之間。但我們想要——我們需要得到他們的確認，我們也非常重要地希望他們就他們希望我們如何定義低血壓事件提供反饋。

Remember, this is a safety study, and the primary endpoint is hypotensive events, comparing the number of hypotensive events between the oral and the GTX-104 IV. So we've asked for their guidance on -- should it be based on what threshold should it be based on systolic only, diastolic or and systolic. So we're really waiting on that. That's really a key piece of information.

請記住，這是一項安全性研究，主要終點是低血壓事件，比較口服和 GTX-104 IV 之間的低血壓事件數量。所以我們已經要求他們提供指導——它應該基於什麼閾值，它應該僅基於收縮壓、舒張壓還是和收縮壓。所以我們真的在等待。這確實是一條關鍵信息。

And finally, as I think you know, we've discussed it. We've asked them to comment on the various exploratory endpoints that we'd like -- or I shouldn't call them endpoints, the various exploratory data that we want to collect. We want to do sparse PK sampling of the patient population to build on our PK/PD modeling. We're going to collect some efficacy in pharmacoeconomic data that really for publication purposes. So really, just a long way of answering your question, but it's really important that we get that clarification before we really finalize the protocol design and start the study.

最後，我想你知道，我們已經討論過了。我們已經要求他們對我們想要的各種探索性終點發表評論——或者我不應該稱它們為終點，即我們想要收集的各種探索性數據。我們希望對患者群體進行稀疏 PK 抽樣，以建立我們的 PK/PD 模型。我們將收集一些真正用於出版目的的藥物經濟學數據。所以說真的，回答你的問題還有很長的路要走，但在我們真正完成協議設計並開始研究之前得到澄清是非常重要的。

And I might have missed it, but did you already have that meeting?

我可能錯過了，但你已經開會了嗎？

No.

不。

Okay. Is that expected? Or are things dragging just at the FDA agency in general? Or has there been some back and forth?

好的。這是預期的嗎？或者一般來說，事情只是在 FDA 機構拖延？或者有一些來回？

Things are dragging absolutely. And the FDA has indicated that they're short staffed. And again, we've had good communication with them. So I just think we expect to get this soon. And as soon as we get it, obviously, we'll be putting out the information that we get.

事情絕對拖沓。 FDA 表示他們人手短缺。再一次，我們與他們進行了良好的溝通。所以我只是認為我們希望盡快得到這個。顯然，一旦我們得到它，我們就會發布我們得到的信息。

Okay. And big picture commercially on 104, as the stuff is going on separately, it's obviously a pretty concentrated market. Has there been further progress in your relationships with the big centers of excellence and the associated KOLs there that theoretically are helping you continue to prime the pump or lay the groundwork for excitement and rapid adoption if and when this thing works and is approved?

好的。 104 的商業大局，因為這些東西是分開進行的，這顯然是一個相當集中的市場。您與大型卓越中心和那裡的相關 KOL 的關係是否有進一步的進展，理論上可以幫助您繼續啟動泵或為興奮和快速採用奠定基礎，如果這件事有效並獲得批准？

Yes. I'll just make a quick comment, and then I'll hand it over to Prashant to expand but as we begin to identify and qualify sites, we're building on relationships we have and expanding those relationships. But let me pass it over to Prashant. Prashant, do you want to add anything there?

是的。我會做一個簡短的評論，然後我會把它交給 Prashant 來擴展，但是當我們開始識別和限定站點時，我們正在建立我們現有的關係並擴展這些關係。但是，讓我將其傳遞給 Prashant。 Prashant，你想在那裡添加什麼嗎？

Sure, Jan. Oren, as Jan mentioned, our strategy is multipronged to prime the market. Obviously, having a prime key opinion leaders, very credible, helping us in that process is very important. And we believe we have a really robust scientific advisory board, prominent neurointensivist from University of Texas in Houston, the largest neurocritical care site in the country with 75 neuro critical care beds, barrel neuroscience, again, very prestigious very prominent site as well center as well and really helping using their systems to help recruit sites, high-volume size, really excites the local PIs at those sites is a big part of our strategy of priming the market.

當然，Jan. Oren，正如 Jan 所提到的，我們的戰略是多管齊下的，以啟動市場。顯然，擁有一位主要的關鍵意見領袖，非常可信，在該過程中幫助我們非常重要。我們相信我們有一個非常強大的科學顧問委員會，來自德克薩斯大學休斯頓的著名神經重症醫師，該國最大的神經重症監護站點，擁有 75 張神經重症監護病床，桶狀神經科學，再次，非常著名的非常著名的站點以及中心很好並真正幫助使用他們的系統來幫助招募站點，大容量，真正激發這些站點的本地 PI 是我們啟動市場戰略的重要組成部分。

The second part of it is as part of conducting the actual study, having these high-volume sites, both comprehensive and advanced stroke center is a combination of them, having them to gain experience for an experience with GTX-104 versus or see the benefits of that. We strongly believe that will provide a great impetus when our product hopefully does get approved and launched that they would become the early adopters.

它的第二部分是作為進行實際研究的一部分，擁有這些高容量站點，綜合和先進的卒中中心是它們的組合，讓他們獲得使用 GTX-104 的經驗或看到好處那個。我們堅信，當我們的產品有望獲得批准並推出時，他們將成為早期採用者，這將提供巨大的推動力。

And in this market, as we have gotten closer to understanding the buying center, if you will, with the P&T committee of a hospital clinical champion and it's a multi stakeholder decision process, we believe that having wins behind our sale with having the early adopters, the key opinion leaders, the thought leaders helping present at medical congresses. We've identified a handful of those where the intensive the neurosurgeons, even the neuroscience nurses, come together and having those talk leaders talk about our program are all things that would really help drive product uptick.

在這個市場上，隨著我們越來越了解購買中心，如果你願意的話，與醫院臨床冠軍的 P&T 委員會一起，這是一個多方利益相關者的決策過程，我們相信，在我們的銷售背後贏得早期採用者，主要意見領袖，幫助出席醫學大會的思想領袖。我們已經確定了一些神經外科醫生，甚至是神經科學護士聚集在一起的地方，讓這些談話領袖談論我們的計劃，這些都是真正有助於推動產品增長的事情。

And the last piece and the least is last but not the least, I mean, is medical communication. Jan mentioned publication strategy, collecting pharmacoeconomic data and then being able to publish those in peer-reviewed journals is also prime to getting the market geared for the product and hopefully a solid uptick once it's on the market.

最後一點也是最不重要的一點是最後但並非最不重要，我的意思是，是醫療交流。 Jan 提到了出版策略，收集藥物經濟學數據，然後能夠在同行評審的期刊上發表這些數據，這也是讓市場適應該產品的首要條件，並有望在產品上市後實現強勁增長。

All right. And lastly, if I may, I apologize for taking so much time. But on 101, are you still expecting with this full clinical report in first half, the -- I guess you called it an exploratory pharmacodynamic efficacy look? And will you share that with us?

好的。最後，如果可以的話，我很抱歉佔用了這麼多時間。但是在 101 上，你是否仍然期待上半年的這份完整的臨床報告——我猜你稱之為探索性藥效學療效觀察？你會和我們分享嗎？

Yes. I'm going to turn that over to Pierre. Pierre, can you respond on that because I'm not sure what the.

是的。我要把它交給皮埃爾。皮埃爾，你能對此做出回應嗎，因為我不確定是什麼。

For, 101. Yes, can you hear me? Hi Oren, thank you for the question. Regarding GTX-101, we're still planning to get the final clinical study report in May. But as you know, we've announced the data, but now it's a question of finalizing the report with all the bells and whistles that an seeing the report. So in terms of the -- I think the PK data were reported and we were comfortable to provide this update before Christmas.

對於，101。是的，你能聽到我說話嗎？嗨，奧倫，謝謝你的提問。關於GTX-101，我們仍計劃在5月份拿到最終的臨床研究報告。但如您所知，我們已經公佈了數據，但現在的問題是最終確定報告，並在看到報告時加入所有花哨的內容。因此，就-我認為 PK 數據已報告，我們很樂意在聖誕節前提供此更新。

Regarding the PD, the pharmacodynamic, it's a little more complicated. Honestly, it was not a primary endpoint of this study. We've looked into some, I would say, attempt to look at pharmacodynamics, so using some bond free assessment. But we'll be able to report a bit of that piece of data, but it's -- I wouldn't -- can I say this we've done this to really find the multiple ascending dose study, which will be the next step. So I mean, we'll be sharing once we have a final report what we believe is really, I would say, relevant in the preparation of the multiple ascending bill. But it's still part of the plan to communicate that information in due time.

關於 PD，藥效學，有點複雜。老實說，這不是這項研究的主要終點。我們已經研究了一些，我想說，試圖研究藥效學，所以使用一些無鍵評估。但我們將能夠報告一些數據，但它是——我不會——我能說我們已經這樣做是為了真正找到多次遞增劑量研究，這將是下一步.所以我的意思是，一旦我們有了最終報告，我們就會分享我們認為真正與多重遞增法案的準備相關的內容。但它仍然是在適當的時候傳達該信息的計劃的一部分。

There are no more questions in the queue. This concludes our question-and-answer session. I'd like to turn the conference back over to management for any closing remarks.

隊列中沒有更多問題。我們的問答環節到此結束。我想將會議轉回管理層聽取任何閉幕詞。

Okay. Thank you, Jason. Again, I just want to thank you all for taking the time to be with us on this call today. We're really excited about the progress we're making to deliver innovative new treatments to thousands of patients who currently lack effective therapies, and we look forward to updating you on our progress towards several key milestones in the coming months. Thank you again, and have a great rest of the day. Back to you, Jason.

好的。謝謝你，傑森。再次，我只想感謝大家今天抽出時間參加我們的電話會議。我們為向目前缺乏有效療法的數千名患者提供創新的新療法所取得的進展感到非常興奮，我們期待著在未來幾個月向您介紹我們在實現幾個關鍵里程碑方面取得的進展。再次感謝您，祝您今天休息愉快。回到你身邊，傑森。

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

謝謝。會議現已結束。感謝您參加今天的演講。您現在可以斷開連接。