DiaMedica Therapeutics Inc (DMAC) 2023 Q4 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the DiaMedica Therapeutics Inc. full year 2023 conference call. An audio recording of the webcast will be available shortly after the call on the Americas website at www.Diomedica.com in the Investor Relations section. Before the company proceeds with its remarks, please note that the Company will be making forward-looking statements on today's call.

早安，女士們、先生們，歡迎參加 DiaMedica Therapeutics Inc. 2023 年全年電話會議。電話會議結束後不久，將在美洲網站 www.Diomedica.com 的投資者關係部分提供網路廣播的錄音。在公司發表評論之前，請注意，該公司將在今天的電話會議上發表前瞻性聲明。

These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these statements. More information, including factors that could cause actual results to differ from projected results appears in the section entitled cautionary statement note regarding forward-looking statements in the company's press release issued yesterday and under the heading Risk Factors in DiaMedica's most recent annual report on Form 10-K. DiaMedica's SEC filings are available at www.sec.gov and on its website.

這些陳述存在風險和不確定性，可能導致實際結果與這些陳述中的預測有重大差異。更多信息，包括可能導致實際結果與預期結果不同的因素，請參閱昨天發布的公司新聞稿中標題為有關前瞻性陳述的警示性聲明說明的部分以及DiaMedica 最新表格10 年度報告中的風險因素標題。-K。DiaMedica 的 SEC 備案文件可在 www.sec.gov 及其網站上取得。

Please also note that any comments made on today's call speak only as of today March 20, 2024 and may no longer be accurate at the time of any replay or transcript re-reading. DiaMedica disclaims any duty to update its forward looking statements following the prepared remarks, we will open the phone lines for questions.

另請注意，今天電話會議中發表的任何評論僅截至 2024 年 3 月 20 日，在重播或重讀文字記錄時可能不再準確。DiaMedica 不承擔在準備好的評論後更新其前瞻性聲明的任何責任，我們將開通電話線路供提問。

I would now like to introduce your host for today's call, Mr. Rick Pauls, DiaMedica's President and Chief Executive Officer. Mr. Pauls, you may begin, sir.

現在我想介紹一下今天電話會議的主持人，DiaMedica 總裁兼執行長 Rick Pauls 先生。保羅斯先生，您可以開始了，先生。

Thank you, Paul. Hello, everyone and welcome to our full year 2023 conference call. I am joined this morning by Lorianne Masuoka our Chief Medical Officer, and Scott Kellen, our CFO. To start off the call this morning, I would like to welcome Lorianne Masuoka as our new Chief Medical Officer. Dr. Masuoka has only been with us for a few short months, but he's already making an enormous impact with clinical sites and building strong momentum with current and potential physician investigators.

謝謝你，保羅。大家好，歡迎參加我們的 2023 年全年電話會議。今天早上，我們的首席醫療官 Lorianne Masuoka 和我們的財務長 Scott Kellen 也加入了我的行列。首先，我謹歡迎 Lorianne Masuoka 成為我們新任首席醫療官。Masuoka 博士只在我們這裡工作了短短幾個月，但他已經對臨床場所產生了巨大影響，並與當前和潛在的醫師研究人員建立了強勁的勢頭。

Dr. Masuoka is a board-certified neurologist with more than 25 years of experience building and expanding high-value pipelines in the biopharmaceutical industry. She has a history of building and leading high-performing teams in clinical development through all stages and the ultimate approval of new medicines.

Masuoka 博士是一位委員會認證的神經科醫生，在生物製藥行業建立和拓展高價值產品線方面擁有超過 25 年的經驗。她擁有在臨床開發各個階段以及新藥最終批准方面建立和領導高績效團隊的歷史。

Her experience also includes playing a key role in developing strategic partnerships and acquisitions of multiple bio technology companies. She has served as the Chief Medical Officer for Epygenix Therapeutics, Marinus Pharmaceuticals, Cubist Pharmaceuticals, now part of Merck and Nektar Therapeutics. She was also an independent board member of Opiant Pharmaceuticals, which was acquired last year for an upfront premium of over 100% and the potential for an approximately 200% premium. If the contingent value rights are achieved. The breadth of our experience includes managing teams in the areas of clinical research, pharmacovigilance, biostatistics and data management, regulatory affairs and clinical operations.

她的經驗還包括在發展策略合作夥伴關係和收購多家生技公司方面發揮關鍵作用。她曾擔任 Epygenix Therapeutics、Marinus Pharmaceuticals、Cubist Pharmaceuticals（現為 Merck 和 Nektar Therapeutics 的一部分）的首席醫療官。她也是 Opiant Pharmaceuticals 的獨立董事會成員，該公司去年以超過 100% 的預付溢價和約 200% 的溢價潛力被收購。如果實現了或有價值權利。我們擁有豐富的經驗，包括臨床研究、藥物警戒、生物統計和資料管理、監管事務和臨床營運領域的管理團隊。

We welcome Lorianne on the call today and I'm thrilled to have her as a key member of our team.

我們歡迎洛麗安今天參加電話會議，我很高興她成為我們團隊的關鍵成員。

Thank you, Rick. I'm excited to join the management team at DiaMedica for several reasons. First, DM199 represents a potential breakthrough in the treatment of acute ischemic stroke, a serious and life-threatening condition for which no new approved medical therapy has emerged. And over 25 years on the basis of the subgroup analyses of the ReMEDy1 study, DM199 shows great promise in returning stroke patients back to baseline neurologic function and preventing recurrent stroke and death. DiaMedica hosted a booth at the International Stroke Conference last month with follow-up requests to our ReMEDy2 trial from over 80 stroke centers.

謝謝你，瑞克。我很高興加入 DiaMedica 的管理團隊，原因有幾個。首先，DM199代表了急性缺血性中風治療的潛在突破，這是一種嚴重且危及生命的疾病，目前尚未出現新的批准的藥物治療方法。25 年來，根據 ReMEDy1 研究的亞組分析，DM199 在使中風患者恢復基線神經功能以及預防復發性中風和死亡方面顯示出巨大的希望。DiaMedica 上個月在國際中風會議上設立了一個展位，並收到了 80 多個中風中心對我們的 ReMEDy2 試驗的後續請求。

11 of those have already requested participation in our trial. They were enthusiastic about DM199 mechanism of action to increase collateral circulation in the area of ischemic damage after stroke without increased risk of hemorrhage. They see DM199 is more like revascularization strategies such as TPA and mechanical thrombectomy and considerably more promising than the many failed neuroprotective agents.

其中 11 人已要求參與我們的試驗。他們對 DM199 的作用機制充滿熱情，該機制可以增加中風後缺血性損傷區域的側支循環，而不增加出血風險。他們認為 DM199 更像是血管重建策略，例如 TPA 和機械血栓切除術，並且比許多失敗的神經保護劑更有希望。

Also at this year's International Stroke Conference. Dr. Scott [Tasmar], DiaMedica as Global Principal Investigator for ReMEDy2 presented a poster in the main hall discussing the ReMEDy2 trial design. Second, the management team and the clinical functions, which I now lead are among the savviest, is hardest working and collaborative with which I have worked. We've also made some strategic additions to the clinical team that have enhanced productivity and effectiveness.

也在今年的國際中風會議上。DiaMedica 的 Scott [Tasmar] 博士作為 ReMEDy2 全球首席研究員在主廳展示了一張海報，討論了 ReMEDy2 試驗設計。其次，我現在領導的管理團隊和臨床職能部門是我所共事過的最精明、工作最努力、協作能力最強的團隊之一。我們也對臨床團隊進行了一些策略性補充，以提高生產力和效率。

Finally, the ReMEDy2 trial is a thoughtfully conceived, well-designed study that is well managed and I believe will provide definitive evidence of whether DM199 can become an important addition to the treatment options for patients who have suffered an ischemic stroke.

最後，ReMEDy2 試驗是一項經過深思熟慮、精心設計、管理良好的研究，我相信它將提供明確的證據，證明 DM199 是否可以成為缺血性中風患者治療選擇的重要補充。

Now let me provide an update on the ReMEDy2 progress as a reminder, our final clinical protocol went into effect in mid November and the first US sites were activated in December 2023. Sites activated in December were our FastTrack centers who were open prior to our clinical hold. And we are now in the process of expanding to a total of 40 to 50 sites in the United States. Once the site expresses interest and we select them it takes approximately three to six months for contracting and IRB approval.

現在讓我提供 ReMEDy2 進展的最新情況作為提醒，我們的最終臨床方案於 11 月中旬生效，第一個美國站點於 2023 年 12 月啟動。12 月啟動的站點是我們的 FastTrack 中心，它們在我們的臨床舉行之前開放。我們現在正在將其在美國的站點總數擴展到 40 到 50 個。一旦網站表達了興趣並且我們選擇了他們，大約需要三到六個月的時間來簽訂合約和 IRB 批准。

New site commitment was slow over the holidays, but beginning in mid January and continuing to the [ICSC] conference in February, we've had a surge of new site commitments. As of today, we have six sites activated with an additional 18 sites in the start-up phase and a deep pipeline of 40 additional sites selected for prequalification business in the US. It's also important to point out that some of the largest and most reputable stroke research hospitals in the country have decided to join our trial.

假期期間，新站點承諾進展緩慢，但從 1 月中旬開始，一直到 2 月的 [ICSC] 會議，我們的新站點承諾激增。截至目前，我們已啟動 6 個基地，另有 18 個基地處於啟動階段，並有 40 個基地被選用於美國資格預審業務。還需要指出的是，國內一些最大、最有信譽的中風研究醫院已經決定加入我們的試驗。

These new centers have substantial patient volumes and clinical research infrastructure and consistently rank among the top enrolling stroke centers in AIS studies. As we move into Q2 and early summer, we expect a substantial ramp-up in opening US sites. Consistent with my past experience in recruiting sites for other studies, we don't expect linear growth in adding new sites and patient volumes and envision more of a hockey stick like ramp up in the US during the second half of 2024 and continuing into 2025.

這些新中心擁有大量患者和臨床研究基礎設施，並且一直位居 AIS 研究中入組人數最多的卒中中心之列。隨著進入第二季和初夏，我們預計美國網站的開幕數量將大幅增加。與我過去為其他研究招募站點的經驗一致，我們預計新站點和患者數量的增加不會出現線性增長，並預計 2024 年下半年美國的增長會像曲棍球棒一樣增加，並持續到 2025 年。

With respect to additional countries in Canada, the Canadian stroke consortium has endorsed our protocol and made recommendations regarding qualified study sites. We have identified six Canadian hospitals to date to participate in ReMEDy2 and can now make our application to Health Canada for approval of our trial. We expect Canadian sites to commence activation in Q3 of this year.

對於加拿大的其他國家，加拿大卒中聯盟已認可我們的方案，並就合格的研究地點提出了建議。迄今為止，我們已確定六家加拿大醫院參與 ReMEDy2，現在可以向加拿大衛生部申請批准我們的試驗。我們預計加拿大站點將於今年第三季開始啟用。

In Australia, the Australian stroke trials network has provisionally endorsed our protocol last week, and we are moving now to flex study sites and initiate regulatory filing activities. We plan to work with many of the same highly engaged centers we work with in remedy one as well as new sites recommended by the network. We expect Australian study sites to commence activating by the end of the year as well. In Europe, including the UK, we have to comply with new rules and requirements related to drug manufacturing quality audits.

在澳大利亞，澳洲中風試驗網絡上週暫時認可了我們的方案，我們現在正在轉向靈活的研究地點並啟動監管備案活動。我們計劃與我們在補救措施中合作的許多相同的高度參與的中心以及網路推薦的新站點合作。我們預計澳洲的研究中心也將在今年年底前開始啟動。在歐洲，包括英國，我們必須遵守與藥品生產品質審核相關的新規則和要求。

We have nearly completed the additional procedures and documentation required. This work needs to be completed prior to seeking European regulatory approval for the study. We plan to pursue sites in select European countries with experienced research teams and potential for significantly higher enrollment rates. We expect to commence site activations late this year.

我們幾乎已經完成了所需的額外程序和文件。這項工作需要在尋求歐洲監管機構批准該研究之前完成。我們計劃在選定的歐洲國家尋找地點，這些國家擁有經驗豐富的研究團隊，並且有可能顯著提高入學率。我們預計將在今年稍後開始站點啟用。

In summary, we expect to have 25 to 30 sites active in recruiting by the end of Q2 and most of the approximately 75 plus sites at the end of 2024. We have been in close contact with our first open sites and we know they are pre-screening patients as we are getting questions on eligibility and participant consenting processes. We anticipate the first post hold participant will be enrolled soon, and it can happen any day now. Then, it's an issue of numbers.

總而言之，我們預計到第二季末將有 25 至 30 個網站活躍於招聘，到 2024 年底將有大約 75 個以上網站中的大多數。我們一直與我們的第一個開放網站保持密切聯繫，我們知道他們正在對患者進行預篩選，因為我們收到了有關資格和參與者同意流程的問題。我們預計第一位持有職位的參與者很快就會註冊，而且隨時都可能發生。然後，就是數字的問題。

As we get more sites up and running, we expect to begin to see enrollment resume and then surge as the bulk of the sites are activated towards the end of the year. I would also point out that some competing trials are concluding in the near future, freeing up critical study center staff bandwidth and likely increasing the patients that can be approached. Given all of this, we are comfortable in now saying, barring any unexpected issues that we anticipate the 144th participant for our interim analysis will be enrolled in Q1 2025.

隨著更多網站的建立和運行，我們預計註冊人數將開始恢復，然後隨著大部分網站在年底前激活，註冊人數將激增。我還想指出，一些競爭性試驗將在不久的將來結束，從而釋放關鍵研究中心工作人員的頻寬，並可能增加可以接觸的患者。考慮到所有這些，我們現在可以放心地說，除非出現任何意外問題，否則我們預計第 144 名參與者將在 2025 年第一季加入我們的中期分析。

I will now turn the call back over to Rick.

我現在將把電話轉回給里克。

Thank you, Lorianne. And I would also remind everyone that as we discussed last quarter, the reason we submitted a protocol revision in October of 2023 was to increase our probability of clinical success. Those changes, including narrowing the focus to patients experiencing moderate strokes, as indicated by the National Institutes of Health Stroke Scale score between 5-15.

謝謝你，洛麗安。我還要提醒大家，正如我們上季度討論的那樣，我們在 2023 年 10 月提交方案修訂的原因是為了增加我們臨床成功的可能性。這些變化包括將關注範圍縮小到經歷中度中風的患者，如美國國立衛生研究院中風量表評分在 5-15 之間所示。

In our Phase 2 ReMEDy1 trial, there were the patients, which demonstrated a greater level of full recovery as measured by the modified Rankin score of 0-1 on a six point scale for there was an 18% improvement of DM199 vs. placebo of this compared to the moderate to moderate severe participants, which showed a 15% improvement versus placebo.

在我們的 2 期 ReMEDy1 試驗中，有一些患者表現出更高水平的完全康復，按照 6 分制的 0-1 的改良 Rankin 評分進行測量，因為 DM199 與安慰劑相比改善了 18%與中度至中度重度參與者相比，與安慰劑相比，改善了15%。

Importantly, we don't believe that this will dramatically reduce the number of eligible stroke patients. We also took measures aimed at reducing the alpha penalty in the interim analysis, and we are confident that these enhancements will provide greater likelihood of clinical success and placed DM199 on the fastest path to FDA approval and importantly, bringing DM199 to stroke patients who have no treatment options today.

重要的是，我們認為這不會大幅減少符合條件的中風患者的數量。我們還採取了旨在減少中期分析中的阿爾法懲罰的措施，我們相信這些增強將提供更大的臨床成功可能性，並使DM199 走上獲得FDA 批准的最快途徑，重要的是，將DM199 帶給沒有症狀的中風患者。今天的治療選擇。

Our clinical team has been working diligently to identify and qualify and engaged physician investigators and clinical sites and ensure that sites feel well supported to conduct this trial. We also recently expanded our clinical operations with the addition of Rebekah de Vitry Fries as our Vice President of Clinical Operations in February. To further expand and strengthen our clinical operations team leadership. Rebekah was previously Head of Clinical Operations at Epygenix Therapeutics.

我們的臨床團隊一直在努力尋找、鑑定和參與醫師研究人員和臨床研究中心，並確保研究中心感受到進行這項試驗的良好支持。我們最近也擴大了我們的臨床業務，二月任命 Rebekah de Vitry Fries 擔任我們的臨床營運副總裁。進一步擴大和加強我們的臨床營運團隊的領導力。Rebekah 曾擔任 Epygenix Therapeutics 的臨床營運主管。

I would like to now turn the call to Scott Kellen to review this quarter's financial results.

我現在想致電斯科特·凱倫（Scott Kellen），請他審查本季的財務表現。

Thanks Rick and good morning, everyone. And thank you for being part of today's call. As Rick mentioned, we announced our full year 2023 financial results and filed our annual report on Form 10-K yesterday. These documents again are both available at either the DiaMedica or the SEC websites.

謝謝瑞克，大家早安。感謝您參加今天的電話會議。正如 Rick 所提到的，我們昨天公佈了 2023 年全年財務業績並提交了 10-K 表格年度報告。這些文件同樣可以在 DiaMedica 或 SEC 網站上找到。

As of December 31, 2023, we reported the total combined cash and investments of $52.9 million, current liabilities of $2.8 million and working capital of $50.9 million. This compares with a total combined cash and investments of $33.5 million, $2.2 million in current liabilities and $31.7 million in working capital as of December 31, 2022. The increases in cash and investments and in working capital were due primarily to the $36.8 million of net proceeds from our private placements in April and June of last year. Of course, partially offset by cash used to fund operating activities during fiscal '23.

截至 2023 年 12 月 31 日，我們報告的現金和投資總額為 5,290 萬美元，流動負債為 280 萬美元，營運資本為 5,090 萬美元。相較之下，截至 2022 年 12 月 31 日，現金和投資總額為 3,350 萬美元，流動負債為 220 萬美元，營運資本為 3,170 萬美元。現金和投資以及營運資金的增加主要是由於去年 4 月和 6 月我們的私募淨收益為 3,680 萬美元。當然，部分被 23 財年用於營運活動的現金所抵銷。

Net cash used in operating activities for the year ended December 31, 2023 was $18.7 million compared to $11.5 million in the prior year. The increase in cash used in operating activities was driven primarily by the company's higher net loss and increased amortization of discounts on purchased marketable securities, partially offset by non-cash share-based compensation and the effects of changes in operating assets and liabilities during '23. We believe that our current cash and investments provide us a runway that will get us to 2026.

截至 2023 年 12 月 31 日止年度，經營活動使用的現金淨額為 1,870 萬美元，而前一年為 1,150 萬美元。經營活動中使用的現金增加主要是由於公司淨虧損增加以及購買有價證券折扣攤銷增加，部分被非現金股份補償以及 23 年經營資產和負債變化的影響所抵消。 。我們相信，我們目前的現金和投資為我們提供了一條通往 2026 年的跑道。

Our research and development expenses increased to $13.1 million for the year ended December 31, 2023, up from $7.8 million for the year ended December 31, 2022. This increase was driven principally by costs incurred for the new studies performed to address the previous clinical hold on our ReMEDy2 trial costs incurred for the Phase 1C study and increased manufacturing and process development costs for DM199. Also contributing to the increase were higher personnel costs, including non-cash share-based compensation associated with expanding the clinical team.

截至2023年12月31日止年度，我們的研發費用增加至1,310萬美元，高於截至2022年12月31日止年度的780萬美元。這一增長主要是由於 1C 期研究產生的 ReMEDy2 試驗成本以及 DM199 的製造和製程開發成本增加而進行的新研究所產生的成本。人員成本上升也是造成這一增長的原因之一，其中包括與擴大臨床團隊相關的非現金股份薪資。

General and administrative expenses were $8.2 million for the year ended December 31, 2023, up from $6.2 million in the prior year. This increase was primarily driven by increased legal fees incurred in connection with the company's lawsuit against PRA and increased personnel costs incurred in conjunction with expanding the Company's team. Increased cost for patent prosecution and non-cash share-based compensation also contributed to the increase.

截至 2023 年 12 月 31 日止年度，一般及行政費用為 820 萬美元，高於前一年的 620 萬美元。這一成長主要是由於公司對 PRA 提起訴訟而產生的法律費用增加，以及因擴大公司團隊而產生的人員成本增加。專利申請成本的增加和非現金股份補償也導致了這種成長。

Other income was $1.9 million for the year ended December 31, 2023, compared to $0.4 million for 2022. This increase was driven by both higher interest rates and increased marketable securities balances in 2023 following our April and June '23 private placements.

截至 2023 年 12 月 31 日止年度的其他收入為 190 萬美元，而 2022 年為 40 萬美元。這一增長是由利率上升以及 2023 年 4 月和 6 月私募之後 2023 年有價證券餘額增加所推動的。

Now before I turn you back over to Rick, let me provide an update on the latest developments with the PRA lawsuit. The three-judge panel recently informed us that they did not find sufficient causal link between PRA's breach of our study agreement and the damages we claimed, we find ourselves in an odd position of having a court finding PRA in breach of the study agreement and that we are entitled to the full results of the study, a judgment which PRA is currently appealing by the way, but not being entitled to at least a return of fees paid under that agreement. So we have until May 6 to notify PRA in the court of a decision to appeal. We are currently evaluating our options.

現在，在我將您轉回給 Rick 之前，讓我先介紹一下 PRA 訴訟的最新進展。由三位法官組成的陪審團最近通知我們，他們沒有發現PRA 違反我們的研究協議與我們索賠的損害賠償之間存在足夠的因果關係，我們發現自己處於一個奇怪的境地，法院認定PRA 違反了研究協議，並且我們有權獲得研究的全部結果，順便說一下，PRA 目前正在對這一判決提出上訴，但至少無權要求退還根據該協議支付的費用。因此，我們必須在 5 月 6 日之前通知法庭 PRA 上訴決定。我們目前正在評估我們的選擇。

And with that, we would like to open the call for questions. Operator, if you could please open the lines now.

至此，我們想開始提問。接線員，如果可以的話，請立即接通線路。

(Operator Instructions)

（操作員說明）

Thomas Flaten, Lake Street Capital.

托馬斯‧弗拉頓（Thomas Flaten），湖街資本公司。

Thank you. Good morning. Appreciate taking the questions. With respect to our patient enrollment of the initial sites were activated in December of last year, and we're looking for first patient soon. Is that something we should expect that from activation to actual patient enrollment we're looking at a three to four month lag. Is that reasonable or is that unique to the fact that the whole study is starting up?

謝謝。早安.感謝接受提問。關於我們的患者登記，最初的站點於去年 12 月啟動，我們很快就會尋找第一位患者。這是我們應該預料到的，從激活到實際患者登記，我們會看到三到四個月的延遲。這是合理的還是整個研究正在啟動這一事實所特有的？

Lorianne? Do you mind taking that one.

洛麗安？你介意拿走那個嗎？

Sure, so as mentioned earlier, many of our study sites are academic institutions and they have multiple layers of IRB approvals and often won't review study contracts until after the IRB approval has been obtained. So we made great progress in opening them shortly after the on clinical hold was lifted and the final protocol was finalized in November, but it does take them some time to get up and running.

當然，正如前面提到的，我們的許多學習中心都是學術機構，它們擁有多層 IRB 批准，並且通常在獲得 IRB 批准之前不會審查學習合約。因此，在臨床擱置解除並於 11 月敲定最終方案後不久，我們在開放它們方面取得了很大進展，但它們確實需要一些時間來啟動和運行。

We have to program their pharmacies to be able to do the intravenous infusion. And that takes a little bit of time and mostly it's a waiting game. It's a it's an issue of numbers. We need to have a lot more critical mass of clinical sites up and ready to enroll because we never know when the great patient is going to come to the emergency room doors.

我們必須對他們的藥房進行編程，使其能夠進行靜脈輸液。這需要一點時間，而且主要是一場等待遊戲。這是一個數字問題。我們需要有更多關鍵數量的臨床站點並準備好註冊，因為我們永遠不知道偉大的患者何時會來到急診室門口。

And another question, given the lag in getting Canada and Australia up and running, it seems that the interim analysis will be heavily weighted towards US patients. Is there any reason to suspect that that would not be representative of the of the full patient enrollment, which will be more represented by Australia, Canada and the EU?

另一個問題是，考慮到加拿大和澳洲的啟動和運作存在滯後性，中期分析似乎將重點放在美國患者身上。是否有任何理由懷疑這不能代表全部病患登記人數，而澳洲、加拿大和歐盟將更多地代表病患登記人數？

Well, we anticipate that there will be a mix of patients because remember, as we said, we anticipate that EU and UK and Canada, Australia will be up and running by the end of the year. So we anticipate full enrollment of the interim analysis of 144 patients to be completed by the end of Q1 of 2025. So there will be a mix of patients, there will be a number of US patients obviously, but we do believe it will be representative.

嗯，我們預計會有各種各樣的患者，因為請記住，正如我們所說，我們預計歐盟、英國、加拿大、澳洲將在今年年底前啟動並運行。因此，我們預計 144 名患者的中期分析將在 2025 年第一季末完成。因此，將會有各種各樣的患者，顯然會有一些美國患者，但我們確實相信這將具有代表性。

Great. Appreciate taking the questions. Thank you.

偉大的。感謝接受提問。謝謝。

Sure.

當然。

François Brisebois, Oppenheimer.

弗朗索瓦·布里斯布瓦，奧本海默。

Can you hear me okay?

你聽得到我說話嗎？

Yes. Frank.

是的。坦率。

Okay, perfect. Sorry, it's funny reception here. So I was just wondering, so first quarter '25 is what we think enrollment will be complete for the interim rate. Can you remind us of your expectations around the interim read and from enrollment, just in terms of the study design, what would make sense from full enrollment to data time line or anything you can share there would be helpful. Thank you.

好的，完美。抱歉，這裡的接待很有趣。所以我只是想知道，所以我們認為 25 年第一季的中期註冊將完成。您能否提醒我們您對中期閱讀和註冊的期望，就研究設計而言，從全面註冊到資料時間線的意義是什麼，或者您可以在那裡分享的任何內容都會有幫助。謝謝。

Sure. So after patient 144 has been dosed, so be a 90 day follow-up. And then after that, they'll be six to seven weeks for database lock and DSMB reviews and and then notice of the resample size.

當然。因此，在 144 號患者服藥後，進行 90 天的追蹤。之後，他們將用六到七週的時間進行資料庫鎖定和 DSMB 審查，然後通知重新採樣大小。

Okay, great. And in terms of expectations of data, can you remind us of possible outcomes? Is it similar to what it used to be or any changes that?

好的，太好了。就數據預期而言，您能否提醒我們可能的結果？是否與以前相似或有何變化？

Sure. So at the interim analysis, if we are not seeing a drug effect, so we're seeing a drug effect of less than approximately 4% versus placebo. The study will be terminated. Otherwise, there will be a resampling size and their sampling size would be between 240 and 728 patients. And so we've had the study powered for a 14% as the base case, which would be approximately 350. So we're seeing a greater effect and then we would anticipate seeing a reduction in the size of we're seeing less of an effect we'd [see an] increase.

當然。因此，在中期分析中，如果我們沒有看到藥物效應，那麼我們會看到與安慰劑相比，藥物效應低於約 4%。研究將被終止。否則，將會進行重新抽樣，抽樣規模將在 240 至 728 名患者之間。因此，我們的研究動力為 14% 作為基本情況，約為 350。因此，我們看到了更大的影響，然後我們預計會看到規模縮小，而我們看到的影響會增加。

Thank you. And then the last question is just in terms of the lawsuit and those fees, do you disclose what those fees were that you were hoping to get reimbursed?

謝謝。最後一個問題是就訴訟和這些費用而言，您是否透露您希望得到報銷的這些費用是多少？

No, Frank. This is Scott. We haven't disclosed any of those details thus far.

不，弗蘭克。這是斯科特。到目前為止我們還沒有透露任何這些細節。

Okay. That's it for me. Thank you.

好的。對我來說就是這樣。謝謝。

Thanks, Rick.

謝謝，瑞克。

Alex Nowak, Craig-Hallum.

亞歷克斯·諾瓦克，克雷格·哈勒姆。

Okay, great. Good morning, everyone. I'm just on the timelines here, timelines did shift to the right by about a quarter here. So I'm just curious what changed versus the prior targets given on the Q3 call.

好的，太好了。大家，早安。我只是在時間線上，時間線確實向右移動了大約四分之一。所以我只是好奇與第三季電話會議上給出的先前目標相比發生了什麼變化。

Sure. So on Q3 call, what we had disclosed that our our CRO had thought that we could complete the interim enrollment by the end of this year and as continued had more time to better understand the projections for site enrollment in particular. And by that, we are now comfortable to actually putting formal guidance as of Q1 2025.

當然。因此，在第三季的電話會議上，我們透露，我們的 CRO 認為我們可以在今年年底前完成臨時註冊，並且繼續有更多時間更好地了解特別是網站註冊的預測。至此，我們現在可以放心地在 2025 年第一季實際發布正式指導意見。

Are you finding that it's harder to-- whether it be activated sites enroll the first patient at a site versus your prior expectation?

您是否發現與您先前的預期相比，啟動站點招募第一位患者是否更困難？

No, no, no change in terms of that.

不，不，這方面沒有任何改變。

Okay. And then and maybe to ask Frank's question a different way is just how much overall has been spent on the PRA lawsuit and how much of a risk is it? I guess if you need to appeal it or you don't appeal it, is an material rest of the cash.

好的。然後，也許可以用不同的方式問 Frank 的問題，即 PRA 訴訟總共花費了多少錢以及風險有多大？我想如果你需要上訴或不上訴，剩下的就是現金了。

And yes, again, we haven't disclosed those numbers specifically other than noted that it's obviously a significant driver of the increase, Alex. And principally what we've got to get our arms around relative to the appeal is can we put any kind of bands or caps on the fees and so that we don't we don't put our current cash runway at risk.

是的，我們沒有具體披露這些數字，只是指出這顯然是成長的重要推動因素，亞歷克斯。相對於上訴，我們必須採取的主要措施是，我們能否對費用設定任何類型的範圍或上限，這樣我們就不會將我們目前的現金跑道置於危險之中。

Okay.

好的。

So in other words, if you if it cost too much if it gave it cost too much that could be a determining factor in moving forward.

換句話說，如果你付出了太多的代價，如果它付出了太多的代價，那可能會成為前進的決定性因素。

If you decide not to move forward with an appeal, I'm sure you must have some sort you must know what the damage amount is generally, I assume it's not material enough to disclose, but right?

如果您決定不繼續上訴，我相信您一定知道損失金額一般是多少，我認為這還不足以透露，但對嗎？

I'm not sure I understand the court found no sufficient causal link. So at this point, if we don't appeal, I don't think they'll change that conclusion.

我不確定我是否理解法院沒有發現足夠的因果關係。所以在這一點上，如果我們不上訴，我認為他們不會改變這個結論。

Okay. Well, I guess I read in the court document, it looked like the core wanted you to paid PRA's legal fees. I'm just trying to understand what their legal fees ultimately is.

好的。嗯，我想我在法庭文件中讀過，看起來核心希望你支付 PRA 的律師費。我只是想了解他們的律師費最終是多少。

No, no, we don't have exposure for that. The Dutch courts operate a little differently. They have an assigned amount that they charged us and we had to pay that. But if it wasn't determined based upon their on their costs, it was around 40,000 US.

不，不，我們沒有這方面的曝光。荷蘭法院的運作方式略有不同。他們向我們收取了指定金額，我們必須支付該金額。但如果不是根據他們的成本來決定的話，大約是四萬美元左右。

Got it. Okay. Thank you so much.

知道了。好的。太感謝了。

Thanks, Alex.

謝謝，亞歷克斯。

And seeing no further questions, I'll turn the call back over to our host.

看到沒有更多問題，我會將電話轉回給我們的主持人。

We would like to thank everyone for joining us this morning. And for your continued support. We're building momentum in our MA trial and look forward for the next update. This concludes our call today. Thank you.

我們要感謝大家今天早上加入我們。感謝您一如既往的支持。我們正在 MA 試驗中積蓄動力，並期待下一次更新。我們今天的電話會議到此結束。謝謝。

The meeting has now concluded. Thank you for joining and have a pleasant day.

會議現已結束。感謝您的加入並祝您有個愉快的一天。