DiaMedica Therapeutics Inc (DMAC) 2024 Q4 法說會逐字稿

Thank you, operator. Hello everyone and welcome to our full year 2024.

謝謝您，接線生。大家好，歡迎來到我們的 2024 年。

Good morning, ladies and gentlemen, and welcome to the DiaMedica Therapeutics full year 2024 conference call. An audio recording of the webcast will be available.

女士們、先生們，早安，歡迎參加 DiaMedica Therapeutics 2024 年全年電話會議。將提供網路直播的音訊錄音。

Shortly after the call today on DiaMedica's website at www.diamedica.com in the investor relations section.

今天電話會議結束後不久，DiaMedica 網站 www.diamedica.com 的投資者關係部分就發布了上述內容。

Before DiaMedica proceeds with its remarks, please note that the company will be making forward-looking statements on today's call. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these statements.

在 DiaMedica 繼續發表評論之前，請注意該公司將在今天的電話會議上發表前瞻性陳述。這些聲明受風險和不確定性的影響，可能導致實際結果與這些聲明中預測的結果有重大差異。

More information, including factors that could cause actual results to differ from projected results, appears in the section entitled Cautionary Note regarding forward-looking statements in the company's press release issued yesterday and under the heading risk factors in Diammedica's 2024 annual report on Form 10-k filed yesterday.

更多信息，包括可能導致實際結果與預期結果不同的因素，請參閱公司昨天發布的新聞稿中關於前瞻性陳述的警告說明部分，以及昨天提交的 Diammedica 2024 年 10-k 表格年度報告中的風險因素標題下。

DiaMedica, SEC filings are available on the SEC's website www.sec.gov and on its website diamedica.com. Please also note that any comments made on today's call speak only as of today, March 18, 2025, 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.

DiaMedica 向美國證券交易委員會 (SEC) 提交的文件可在美國證券交易委員會 (SEC) 網站 www.sec.gov 和 diamedica.com 上查閱。另請注意，今天電話會議上發表的任何評論均截至 2025 年 3 月 18 日有效，在重播或重新閱讀會議記錄時可能不再準確。DiaMedica 不承擔更新其前瞻性聲明的任何義務。

Following the prepared remarks, the phone lines will be open for questions. I would now like to turn you over to your host for today's call, Mr. Rick Pauls, DiaMedica's President and Chief Executive Officer.

準備好的發言結束後，電話熱線將開放，接受提問。現在，我想將今天的電話會議主持人、DiaMedica 總裁兼執行長 Rick Pauls 先生交給您。

Thank you, operator. Hello, everyone, and welcome to our full year 2024 conference call. I'm joined this morning by Scott Kellen, our Chief Financial Officer, and Dr. Lorianne Masuoka, our Chief Medical Officer. We're happy to be here today to update you on the progress of our two main clinical development programs. Seeing that our next expected clinical milestone is for our preeclampsia study, I'll ask Lorianne to start with an update on our preeclampsia program, and then we'll turn to our stroke study.

謝謝您，接線生。大家好，歡迎參加我們的 2024 年全年電話會議。今天上午，與我一起參加會議的還有我們的財務長 Scott Kellen 和首席醫療官 Lorianne Masuoka 博士。我們很高興今天在這裡向您通報我們兩個主要臨床開發項目的進展。鑑於我們預期的下一個臨床里程碑是先兆子癇研究，我將要求 Lorianne 首先介紹先兆子癇計劃的最新進展，然後我們將轉向中風研究。

Thanks, Rick. Starting with preeclampsia, we are very pleased with our progress in this clinical program. Less than a year ago, our collaborators submitted the first draft of the protocol to the Tygerberg Hospital's ethics Board. Since then, we have obtained ethics approval, clearance from the South African Health Products Regulatory Authority, South Africa's equivalent of the US FDA and have begun dosing preeclampsia mothers.

謝謝，里克。從子癇前症開始，我們對這個臨床計畫的進展感到非常滿意。不到一年前，我們的合作者向泰格伯格醫院的倫理委員會提交了該協議的初稿。從那時起，我們獲得了道德批准，獲得了南非衛生產品監管局（相當於美國 FDA）的批准，並開始為子癇前症母親提供藥物。

This marks the first study of DM199 in a pregnancy-related condition, a vulnerable setting where both the mother and fetus are considered patients. We believe these significant accomplishments within a short time frame underscore DM199 potential as a treatment for this serious condition.

這是首次針對 DM199 在妊娠相關疾病的研究，妊娠相關疾病是一種脆弱的環境，母親和胎兒都被視為患者。我們相信，這些在短時間內取得的重大成就凸顯了 DM199 作為治療這種嚴重疾病的潛力。

All of this was made possible by the strong collaborations we've built with leading KOLs and trialists. Our partners at the University of Melbourne and Stellenbosch University were immediately drawn to DM199 for its promising safety profile, its ability to produce nitric oxide, and its potential to lower blood pressure.

這一切都得益於我們與領先的 KOL 和試用者建立的緊密合作。我們在墨爾本大學和斯泰倫博斯大學的合作夥伴立即被 DM199 所吸引，因為它具有良好的安全性、產生一氧化氮的能力以及降低血壓的潛力。

Most notably, DM199 is a protein of a sufficiently large molecular size that it is not expected to cross the placental barrier, offering a key safety advantage for the developing fetus. In contrast, small molecule anti-hypertensives passively diffuse across the placental barrier, and some are contraindicated in pregnancy because they cause fetal harm. We have repeatedly demonstrated that DM199 can lower blood pressure in humans and believe that this supports the hypothesis that DM199 can lower blood pressure in pregnant women.

最值得注意的是，DM199 是一種分子量足夠大的蛋白質，預計不會穿過胎盤屏障，這為發育中的胎兒提供了關鍵的安全優勢。相較之下，小分子抗高血壓藥物會被動擴散穿過胎盤屏障，有些藥物在懷孕期間是禁忌的，因為它們會對胎兒造成傷害。我們已反覆證明DM199可以降低人類血壓，並認為這支持DM199可以降低孕婦血壓的假設。

Compared to other therapeutic areas like oncology, which have advanced more rapidly in recent years, the treatment of pregnancy complications remains outdated. No FDA approved treatments exist for preeclampsia, despite the growing burden of this disease. To our knowledge, DM199 is the only novel agent currently being dosed in pregnant women with preeclampsia.

與近年來發展更快的腫瘤學等其他治療領域相比，妊娠併發症的治療仍然過時。儘管先兆子癇的盛行率日益增加，但目前尚無 FDA 核准的治療方法。據我們所知，DM199 是目前唯一一種用於治療子癇前症孕婦的新型藥物。

Existing blood pressure medications used in preeclampsia do not enhance nitric oxide signaling, which is critically impaired, leading to reduced blood flow to the fetus. Nor do they improve preeclamptic endothelial dysfunction. They merely manage symptoms. Preeclampsia is a progressive disease, and these outdated treatments lose effectiveness or fail over time.

目前用於治療子癇前症的降血壓藥物無法增強一氧化氮訊號，而一氧化氮訊號嚴重受損，導致流向胎兒的血流量減少。它們也不能改善子癇前症內皮功能障礙。他們僅僅控制症狀。子癇前症是一種進行性疾病，這些過時的治療方法會隨著時間的推移而失去效果或失敗。

By augmenting nitric oxide signalling, we hope that DM199 can not only lower blood pressure but also improve underlying endothelial dysfunction, offering benefits such as increased blood flow to the fetus and reduction of dangerously high blood pressure in the mother going beyond symptom management.

透過增強一氧化氮訊號，我們希望 DM199 不僅可以降低血壓，還可以改善潛在的內皮功能障礙，提供諸如增加胎兒血流量和降低母親危險的高血壓等益處，而不僅僅是症狀管理。

For context on the limitations of existing hypertension treatments, the Preserve 1 study of early onset preeclampsia in the United States found that approximately 50% of women delivered within five to six days of study enrollment due to refractory or uncontrolled hypertension, despite receiving maximal intervention.

關於現有高血壓治療的局限性，美國早發性子癇前症的 Preserve 1 研究發現，儘管接受了最大程度的干預，但仍約有 50% 的婦女在研究開始後的五到六天內因難治性或未控制的高血壓而分娩。

On average, participants delivered before 30 weeks of gestation, exposing the baby to significant risks. This highlights the aggressive and progressive nature of preeclampsia and underscores the urgent need for therapies that can successfully manage symptoms and ultimately go beyond this to target the underlying endothelial dysfunction. At these early gestational ages, every additional day of prolonging pregnancy is crucial.

平均而言，參與者在懷孕 30 週之前分娩，這使嬰兒面臨重大風險。這凸顯了子癇前症的侵襲性和進行性，並強調迫切需要能夠成功控制症狀並最終超越這一點以針對潛在的內皮功能障礙的治療方法。在妊娠早期，延長妊娠的每一天都至關重要。

Turning now to our investigator sponsored phase 2 trial, we are currently dosing women in Part 1A, the dose escalation portion of the study. Each dose cohort consists of three patients. If no safety concerns arise, we proceed to the next cohort at a higher dose. Part 1A may include up to 10 cohorts with the lowest IV dose starting at 0.1 mcg per kilogram and the highest at 2.5 mcg per kilogram. For reference, our IV dose in the stroke program is 0.5 mcg per kilogram.

現在轉到我們的研究者發起的第 2 階段試驗，我們目前正在對第 1A 部分（研究的劑量遞增部分）中的女性進行給藥。每個劑量組由三名患者組成。如果沒有出現安全問題，我們將以更高的劑量進行下一組治療。第 1A 部分可能包括最多 10 個隊列，最低 IV 劑量為每公斤 0.1 微克，最高為每公斤 2.5 微克。作為參考，我們中風治療計畫中的靜脈注射劑量為每公斤 0.5 微克。

Once a dose is identified in Part 1A that achieves clinically meaningful blood pressure reductions without causing hypotension, we will advance to Part 1B, an expansion cohort of 30 additional patients designed to confirm the optimal dose. We are pleased to report that multiple dosing cohorts in Part 1A have been completed, with DM199 appearing to be well tolerated and no serious adverse events or signs of pathological hypotension being reported. We look forward to showing results from Part 1A, which we anticipate in the second quarter.

一旦在第 1A 部分中確定了能夠實現臨床意義上的血壓降低且不會引起低血壓的劑量，我們將進入第 1B 部分，這是一個由另外 30 名患者組成的擴展隊列，旨在確認最佳劑量。我們很高興地報告，第 1A 部分的多個給藥組已經完成，DM199 似乎耐受性良好，並且沒有報告嚴重不良事件或病理性低血壓的跡象。我們期待展示第 1A 部分的結果，預計將在第二季公佈。

Turning to our stroke program, we are pleased to announce that we have activated 30 clinical sites which we describe as our critical mass to generate a more steady stream of enrollments. Increasing overall activity levels in communications between sites is important in creating that healthy professional competition to keep our study front of mind amongst our study sites.

談到我們的中風項目，我們很高興地宣布，我們已經啟動了 30 個臨床站點，我們將其描述為臨界規模，以產生更穩定的招生流。提高站點之間溝通的整體活動水平對於創造健康的專業競爭非常重要，這可以使我們的研究在研究站點中保持領先地位。

I would also note that the bulk of these sites are operating under our protocol version 5.0. This version of the protocol, among other things, allows DM199 to be stored at refrigerated temperature and expands the eligible population to include patients not responding to thrombolytic treatment.

我還要指出的是，這些機構大部分都按照我們的5.0版方案運作。此方案允許DM199在冷藏溫度下儲存，並將適用族群擴大到對溶栓治療無反應的患者。

Refrigerated storage enables the study drug to be sent with the participant when they leave the hospital, potentially simplifying the logistics of the participant receiving their subcutaneous injections for the entire three week treatment period. And for patients who haven't improved for at least six hours after thrombolytic treatment, providing the remaining enrolment criteria are met, they may be enrolled in our trial.

冷藏儲存使研究藥物能夠在參與者離開醫院時隨他們一起發送，這可能簡化參與者在整個三週治療期間接受皮下注射的後勤工作。對於接受溶栓治療後至少六小時病情仍未改善的患者，只要符合其餘入選標準，即可參加我們的試驗。

This change, in addition to increasing the number of potential patients for ReMEDy2, brings in a patient population that can be a good group for evaluation in our trial. In our initial stroke trial, ReMEDy1, post hoc analysis of similar participants showed the most favourable improvement in the rate of full or nearly full recovery.

這項變化除了增加 ReMEDy2 的潛在患者數量外，還帶來了一群可作為我們試驗評估的良好群體的患者。在我們最初的中風試驗 ReMEDy1 中，對類似參與者的事後分析顯示，完全或接近完全康復的速度有最有利的提高。

The protocol also allows for enrolment of patients with occlusions of the M2 segment of the middle cerebral artery and the posterior arteries. This is a very significant change given the recent negative results of three mechanical thrombectomy of middle-sized vessel occlusion studies announced at the ISD conference last month. I can share with you that sites are very positive about version 5 of the protocol.

該協議還允許招募大腦中動脈 M2 段和後動脈閉塞的患者。鑑於上個月在 ISD 會議上宣布的三項中型血管閉塞機械血栓切除術研究的最新結果均為陰性，這是一個非常重大的變化。我可以告訴你們，網站對協議第 5 版持非常積極的態度。

Building on this, our clinical and medical affairs teams continue to work on ensuring that once activated, study sites feel comfortable and well supported to enrol participants. In particular, they need to be comfortable that any participant they enrol will be able to receive treatment through the three week dosing period as the participant moves from the hospital to any intermediate care facility and ultimately home.

在此基礎上，我們的臨床和醫療事務團隊將繼續努力確保研究地點一旦啟動，就能感到舒適並獲得良好的支持以招募參與者。特別是，他們需要確保他們招募的任何參與者都能夠在從醫院轉移到任何中級護理機構並最終回到家的三週給藥期內接受治療。

Developing this comfort level requires a great deal of personal contact between our clinical team and the study sites. By the end of last year, we had a wide variety of resources available to provide any assistance the site might require and open lines of communication to ensure that the sites are aware of such options.

要達到這種舒適度，需要我們的臨床團隊和研究地點之間進行大量的個人接觸。截至去年年底，我們已擁有各種各樣的資源，可以為該遺址提供可能需要的任何幫助，並開通了溝通管道，以確保該遺址了解這些選擇。

Complementing these efforts, our medical affairs team has been investing time meeting in person with study teams to discuss the potential benefits of DM199 and the importance of the ReMEDy2 trial. This is done in a lunch and learn format to maximize the number of site personnel that can hear and engage with us on the trial.

除了這些努力之外，我們的醫療事務團隊還投入時間與研究團隊進行面對面會談，討論 DM199 的潛在益處和 ReMEDy2 試驗的重要性。這項工作以午餐和學習的形式進行，以最大限度地增加現場人員在試驗中聽取和參與我們的活動的數量。

The team has also been coordinating peer to peer calls between study coordinators so that these professionals can share directly with each other thoughts and ideas on the things that work and don't work in managing participants through the study. Members of senior management have also been visiting the sites projected to be high-end rollers.

團隊也一直在協調研究協調員之間的點對點通話，以便這些專業人員可以直接分享在研究中管理參與者時有效和無效的事情的想法和觀點。高階主管也已視察了計劃興建高階滾輪廠的場地。

As we look back on the progress we've made to date, we note that even with highly interested physician investigators, it has been and is taking significantly more time to get sites through the engagement, planning, and set up process. We believe this is related to lower staffing levels in research units in this post-COVID world. In hindsight, our expectation that restoring support for research at study sites would have been a higher priority, but in the end, we underestimated the required startup time.

當我們回顧迄今為止所取得的進展時，我們注意到，即使有非常感興趣的醫生研究人員，也需要花費更多的時間才能讓站點完成參與、規劃和設置過程。我們認為這與後疫情時代研究部門人員配備水準較低有關。回想起來，我們原本期望恢復對研究地點的研究支持是更高的優先事項，但最終我們低估了所需的啟動時間。

As I described, we've increased our level of engagement to overcome these issues, and though we're very encouraged by the uptick in enrolments in 2025, we've updated our expectations for the interim analysis for the first half of 2026. We'll provide a further update after we hit enrolment of 25%.

正如我所描述的，我們已經提高了參與度來克服這些問題，儘管我們對 2025 年入學人數的上升感到非常鼓舞，但我們已更新了對 2026 年上半年中期分析的預期。當入學率達到 25% 時，我們將提供進一步的更新。

In other ReMEDy2 related developments, we've had a great experience at the February 2025 International Stroke Conference. This was held in Los Angeles, and our booth received considerable attention, and we hosted a reception for our current and potential study sites, which was very well attended.

在其他與 ReMEDy2 相關的發展中，我們在 2025 年 2 月的國際中風會議上獲得了豐富的經驗。該活動在洛杉磯舉行，我們的展位受到了廣泛關注，我們為當前和潛在的研究地點舉辦了招待會，出席人數眾多。

At this conference, results from three studies of mechanical thrombectomy and medium vessel occlusions were announced. None of the studies reported success. These results have the potential to benefit ReMEDy2 enrolment in that these patients are candidates for our trial. The European Stroke Conference is coming up in May, and we look forward to another opportunity to build awareness of the DM199 and our ReMEDy2 trial.

本次會議公佈了機械血栓切除術和中型血管閉塞術三項研究的結果。沒有任何研究報告成功。這些結果有可能使 ReMEDy2 的招募受益，因為這些患者都是我們試驗的候選人。歐洲中風會議將於五月召開，我們期待有另一個機會提高人們對 DM199 和我們的 ReMEDy2 試驗的認識。

And as we announced yesterday, the scheduled safety review of the new IV dosing rates implemented upon resumption of our trial was completed in January. Our independent data safety monitoring board conducted a comprehensive review of safety data from all then enrolled participants, and no significant safety concerns were identified. Their conclusion was that the ReMEDy2 trial should continue without modification.

正如我們昨天宣布的那樣，我們在恢復試驗後實施的新的靜脈注射給藥率的預定安全審查已於一月份完成。我們獨立的資料安全監控委員會對所有當時登記的參與者的安全資料進行了全面審查，並沒有發現重大安全問題。他們的結論是，ReMEDy2 試驗應該繼續進行，無需修改。

Also in February, a paper providing an analysis of the mechanism of action of DM199 and its potential benefit for AIS patients appeared in a peer reviewed publication entitled Recombinant Human Tissue Carine I for Treating Acute Ischemic Stroke and Preventing Recurrence.

同樣在 2 月份，一篇同行評審的出版物發表了一篇論文，題為《重組人組織 Carine I 用於治療急性缺血性中風和預防復發》，該論文分析了 DM199 的作用機制及其對 AIS 患者的潛在益處。

This publication is now available online and was published in the February 2025 issue of Stroke. This paper provides scientific insight into DM199's mechanism for increasing collateral circulation and salvaging brain tissue at risk from infarction following an AIS.

該出版物現已在線提供，並發表在 2025 年 2 月的《Stroke》雜誌上。本文對 DM199 增加側支循環和挽救 AIS 後梗塞風險腦組織的機制提供了科學見解。

I'll now turn the call back to Rick.

我現在將電話轉回給里克。

Thanks Lorianne. I want to take a minute to thank Mr. Dan O'Connor for recently joining our Board. He's a tremendously accomplished leader in biotech and in particular in building companies. We're grateful to have his wisdom and guidance as we move DiaMedica and DM199 forward, and we'll take every opportunity to learn from his past successes.

謝謝 Lorianne。我想花一點時間感謝丹·奧康納先生最近加入我們的董事會。他是生物技術領域，尤其是在公司創建領域，一位非常有成就的領導者。我們很感激在推動 DiaMedica 和 DM199 發展的過程中得到他的智慧和指導，我們將抓住一切機會學​​習他過去的成功經驗。

Before I turn the call over to Scott. I'd like to add that our team really believes DM199 will be an effective treatment for both stroke and preeclampsia patients. I would also like to recognize our team's hard work and accomplishments over the past year, and I look forward to continuing working with the team as we advance our clinical programs.

在我把電話轉給斯科特之前。我想補充一點，我們的團隊確實相信 DM199 將成為治療中風和子癇前症患者的有效方法。我還要表彰我們團隊在過去一年中的辛勤工作和成就，並期待在我們推進臨床專案的過程中繼續與團隊合作。

Know that we are fully committed to moving both clinical programs forward as we have an important opportunity to provide options for patients who currently have no therapeutic treatment options today.

請知悉，我們全力致力於推動這兩個臨床計畫的發展，因為我們有一個重要的機會為目前沒有治療選擇的患者提供選擇。

Now I'd like to hand the call over to Scott Kellen to review this quarter's financial results.

現在我想把電話交給史考特·凱倫來回顧本季的財務結果。

Thanks, Rick, and good morning everyone.

謝謝，里克，大家早安。

As the operator mentioned, we announced our full year '24 financial results and filed our annual report on Form 10-k yesterday. These documents are both available on either the DiaMedica or the SEC website.

正如營運商所提到的，我們昨天公佈了 24 年全年財務業績並提交了 10-k 表格年度報告。這些文件均可在 DiaMedica 或 SEC 網站上找到。

As of December 31, 2024, we've reported a total combined cash and investments of $44.1 million. Current liabilities of $5.4 million and working capital of 39.2. This compares to a total combined cash and investments of $52.9 million. $2.8 million in current liabilities, and $50.9 million in working capital as of the end of December 31, 2023.

截至 2024 年 12 月 31 日，我們報告的現金和投資總額為 4,410 萬美元。流動負債為 540 萬美元，營運資本為 3,920 萬美元。相較之下，截至 2023 年 12 月 31 日，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。

The decreases in combined cash and investments and in working capital were due primarily to the cash used to fund our operations partially offset by net proceeds received from the approximately $12 million private placement we completed in June of 2024.

合併現金和投資以及營運資本的減少主要是由於用於資助我們營運的現金，部分被我們在 2024 年 6 月完成的約 1,200 萬美元私募所收到的淨收益所抵消。

Net cash used in operating activities for the full year '24 was $22.1 million compared to $18.7 million for the full year '23. The increase in cash used in operating activities was driven by the combination of our increased net loss and the advance of deposit funds to vendors supporting our ReMEDy2 trial during 2024.

24 年全年經營活動所用淨現金為 2,210 萬美元，而 23 年全年為 1,870 萬美元。經營活動現金流的增加是由於我們的淨虧損增加以及在 2024 年向支持我們的 ReMEDy2 試驗的供應商預付押金所致。

These were partially offset by changes in operating assets and liabilities during 2024, particularly the increase in accrued liabilities related to our ReMEDy2 trial and ongoing manufacturing development activities as of December 31, 2024. We anticipate that our current cash and investments provide us a runway into Q3 of 2026.

這些部分被 2024 年經營資產和負債的變化所抵消，特別是截至 2024 年 12 月 31 日與我們的 ReMEDy2 試驗和正在進行的製造開發活動相關的應計負債的增加。我們預計，我們目前的現金和投資將為我們進入 2026 年第三季提供支撐。

Turning to the income statement, our research and development expenses increased to $19.1 million for the year end of December 31, 2024, up from $13.1 million in the prior year. This increase resulted primarily from cost increases driven by the continuation of the ReMEDy2 clinical trial, the expansion of the clinical team, and increased manufacturing and development activity.

談到損益表，我們的研發費用從上一年的 1,310 萬美元增加到 2024 年 12 月 31 日結束的年度的 1,910 萬美元。這一增長主要源於 ReMEDy2 臨床試驗的持續、臨床團隊的擴大以及製造和開發活動的增加所導致的成本增加。

Partially offsetting these increases were cost reductions related to the completion of prior clinical and non-clinical trial work in 2023. We expect that R&D expenses will increase moderately relative to recent prior periods as the company expands ReMEDy2 globally and continues our site activation and enrollment activities and as we continue to pursue our DM199 clinical development program into preeclampsia.

部分抵消這些增長的是與 2023 年完成先前臨床和非臨床試驗工作相關的成本降低。我們預計，隨著公司在全球擴展 ReMEDy2 並繼續我們的站點激活和註冊活動，以及我們繼續將 DM199 臨床開發計劃應用於先兆子癇，研發費用將相對於近期適度增加。

Our general and admitting rate of expenses were $7.6 million for the full year of 2024, down from $8.2 million for the full year 2023.

2024 年全年我們的一般及入院費用為 760 萬美元，低於 2023 年全年的 820 萬美元。

This decrease was driven primarily by the combination of decreased legal fees incurred in connection with our lawsuit against PRA Netherlands and reductions in directors’ and officers' liability insurance premiums. These decreases were partially offset by increased personnel costs associated with expanding our team and increased non-cash share-based compensation costs. DiaMedica expects G&A expenses to remain steady compared to prior periods.

這一下降主要是由於我們針對 PRA Netherlands 的訴訟所產生的法律費用減少以及董事和高管責任保險費減少所致。這些減少部分被與擴大團隊相關的人員成本增加以及非現金股份薪酬成本增加所抵銷。DiaMedica 預計，與前期相比，一般及行政費用將保持穩定。

Our net other income for the full year of 2024 was $2.3 million compared to $1.9 million for 2023. This increase was driven by a higher level of interest income being recognized related to higher average marketable security balances during 2024 as compared to the prior year.

我們 2024 年全年的淨其他收入為 230 萬美元，而 2023 年為 190 萬美元。這一增長是由於 2024 年與上一年相比，平均有價證券餘額增加，導致確認的利息收入水準提高。

With that, let me ask the operator to open the lines for questions.

現在，請容許我請接線生開通問答專線。

(Operator Instructions)

（操作員指示）

Thomas Flaten, Lake Street.

托馬斯·弗拉頓，湖街。

Good morning. I appreciate you taking the questions. Lorianne, a couple for you on ReMEDy2 of the 30 sites that are activated, how many of those are the top 15 sites that you've previously identified and how many of the 30 are actively enrolling versus being activated?

早安.感謝您回答這些問題。Lorianne，關於 ReMEDy2，在已啟動的 30 個站點中，有多少個是您之前確定的前 15 個站點，以及這 30 個站點中有多少個是正在積極註冊而不是處於啟動狀態？

So of the 30 active or of the 30 sites that we've identified and activated, the Top 15 comprise about, 13 or so the vast majority of the Top 15 are activated, and many of them are currently enrolling.

因此，在我們確定並激活的 30 個活躍站點中，排名前 15 的站點約佔 13 個，其中絕大多數已激活，其中許多站點目前正在註冊。

Got it. And then with respect to the DSMB review that you said, I believe you said was completed in January, how much data did they have on those patients?

知道了。然後關於您所說的 DSMB 審查，我相信您說該審查已於 1 月完成，他們掌握了這些患者的多少數據？

Was it just from the very acute phase or did they have a full treatment period to review for safety?

是剛從非常急性的階段開始，還是他們有一個完整的治療期來審查安全性？

So they had the entire database, which means that all of the data that had been entered for those patients were available to the DSMB. What we do is we establish a cutoff date and then after that cutoff date we look at all of the data for that patient. So, it's their entire experience that they have experienced that they have gone through up until that cutoff date.

因此他們擁有整個資料庫，這意味著 DSMB 可以獲得這些患者的所有數據。我們所做的是確定一個截止日期，然後在該截止日期之後查看該患者的所有數據。所以，這是他們在截止日期之前所經歷的全部經歷。

Understood excellent, thank you for taking the questions. I'll get back in the queue.

理解得很好，感謝您回答這些問題。我會回到隊列中。

Chase Knickerbocker, Craig-Hallum.

蔡斯·尼克博克、克雷格·哈勒姆。

Good morning. Thanks for taking the questions. Sorry if I make you repeat some details here, but, maybe just help us out with a couple of the assumptions to kind of get us to a first half '26 interim assessment, just maybe relative to kind of the last kind of updates we received.

早安.感謝您回答這些問題。抱歉，如果我讓您在這裡重複一些細節，但也許只是幫助我們做出幾個假設，以便讓我們對 26 年上半年進行中期評估，也許只是相對於我們收到的最後一種更新而言。

I mean, what are your expectations around. Enrolment rates, and as we look at these 30 centres, I mean, what is kind of your ultimate expectation for trial sites activated, and thanks start there?

我的意思是，你對此有什麼期望。入學率，當我們看這 30 個中心時，我的意思是，您對啟動的試驗點的最終期望是什麼，從那裡開始？

So we have 30 sites that are currently active in the United States, but please remember that we are going to also that we also have five centres that are very active in Georgia. We are going to be opening sites in Canada in the next few weeks, and we're also going to be moving into Australia and into Europe.

因此，我們目前在美國有 30 個活躍的站點，但請記住，我們還將在喬治亞州擁有 5 個非常活躍的中心。我們將在未來幾週內在加拿大開設網站，並且還將進軍澳洲和歐洲。

So we'll have more than 30 sites, what we anticipate from the interim analysis is the opportunity. The reason why we increased our sample size from 144 to 200 was the opportunity to decrease the sample size that is needed overall. So, for example, originally, we were looking at a 14% improvement over placebo and with a 364 patient.

因此，我們將擁有 30 多個站點，從中期分析中我們預計會有機會。我們將樣本量從 144 增加到 200 的原因是為了減少總體所需的樣本量。例如，最初，我們觀察到 364 名患者的情況比安慰劑有 14% 的改善。

Population with the 200 interim analysis we have the possibility if we see that same efficacy rate of having only 300 patients. So we anticipate that the in term analysis, although delayed as compared to the original in term analysis in large part due to increasing the sample size for the inter lysis, could overall save us time and money by reducing the sample size.

透過對 200 名患者進行中期分析，我們有可能看到，即使只有 300 名患者，其療效也是一樣的。因此，我們預計，雖然與原始的期中分析相比，期中分析會延遲，這在很大程度上是由於增加了期中裂解的樣本量，但透過減少樣本量，總體上可以節省我們的時間和金錢。

On the overall number of sites, how high do you expect to go at this point and then on the kind of enrolment rate, can you just kind of help us on how we should think about it with the kind of existing sites and kind of your experience kind of ramping these up now as far as kind of what gets us to that first half '26 interim?

就站點總數而言，您預計目前會達到多少，然後就入學率而言，您能否幫助我們，根據現有的站點類型，考慮一下我們應該如何考慮這個問題，以及您現在如何擴大這些站點的經驗，以及是什麼讓我們達到 26 年上半年的中期目標？

Yeah, so we're anticipating doubling the number of sites that we are going to be having enrolling, and we currently are targeting, we are currently targeting sites that can enrol about one to two patients per month.

是的，因此我們預計招募的站點數量將增加一倍，我們目前的目標是，我們目前的目標是每月可以招募一到兩名患者的站點。

And of the sites that we've enrolled so far, kind of what number of those are kind of at that kind of rate of one to two per month at this point and kind of is there an idea of kind of how long it takes at this point to kind of get them to that rate?

到目前為止，我們已經註冊的網站中，有多少個網站目前處於每月一到兩個的速度，您是否知道目前需要多長時間才能達到這個速度？

It generally takes about 6 to 12 months to get a site up and running, and once they're up and running, it takes several weeks for them to start activating and enrolling because they need to get everything ready for enrolment into the trial.

通常，建立網站並運行大約需要 6 到 12 個月的時間，一旦建立並運行，他們就需要幾週的時間才能開始啟動和註冊，因為他們需要做好一切準備才能參加試用。

We're not at the moment disclosing how many of those sites are enrolling, how many patients will give you a fuller picture when we hit 25% enrolment.

我們目前還沒有透露有多少站點正在招募患者，當我們達到 25% 的招募率時，有多少患者會給你更全面的資訊。

Great thank you.

非常感謝。

Francois Brisebois, Oppenheimer.

弗朗索瓦·布里斯博瓦，奧本海默。

Hi, this is Dan from Frank. Thanks for taking our questions. Since the amendments from that were disclosed last time, particularly with regard to the tPA nonresponders, are you starting to see an improvement in the enrolment rate in this particular subpopulation among the activated sites? Yeah, and I have one follow up.

嗨，我是弗蘭克的丹。感謝您回答我們的問題。自從上次披露了相關修正案，特別是關於 tPA 無反應者的部分，您是否開始看到在已激活站點中這一特定亞群的入學率有所提高？是的，我還有一個後續問題。

Sure, Dan, yeah, so since the beginning of the year we have seen a very encouraging increase in terms of enrolment. It's still not where we want to be at, but definitely a significant increase that has been driven in part with this protocol amendment where we are including patients that receive tPA that do not respond.

當然，丹，是的，所以自今年年初以來，我們看到入學人數出現了非常令人鼓舞的增長。這仍未達到我們想要的效果，但肯定是一個顯著的增長，部分原因是這項協議修正案將接受 tPA 治療但沒有反應的患者納入其中。

M2 patients and so keep in mind that for the protocol version 5, most of the activation of those that protocol occurred at the end of 2024 and then coming into early into the new year.

M2 患者，因此請記住，對於協議版本 5，該協議的大部分活化發生在 2024 年底，然後進入新年初。

Thank you. And just in regards to the recent ISD conference that you highlighted, could you give us some more color on like the KOLs feedback on DM199 in light of the other studies that were reported there at the conference?

謝謝。關於您強調的最近的 ISD 會議，您能否根據會議上報告的其他研究，向我們詳細介紹 KOL 對 DM199 的回饋？

Sure, I mean, as Lorianne mentioned in the prepared remarks, is that the big takeaway was that there was a lot of excitement before the conference on mechanical thrombectomy for these MIEBO study patients. So these are medium vessels, typically the M2s, and most of the physicians had thought that those studies would be very positive and would have potentially had a negative impact in terms of our trial and our patient population.

當然，我的意思是，正如 Lorianne 在準備好的發言中提到的那樣，最大的收穫是，在會議召開之前，人們對這些 MIEBO 研究患者的機械血栓切除術感到非常興奮。因此，這些都是中等大小的血管，通常是 M2，大多數醫生認為這些研究會非常積極，但可能會對我們的試驗和患者群體產生負面影響。

The fact that 3 of those studies failed, one of them actually showed some safety concerns, was very encouraging for our sites, our Scientific Advisory Board.

其中三項研究失敗，其中一項研究實際上顯示出一些安全問題，這對我們的網站、我們的科學顧問委員會來說非常令人鼓舞。

Beyond that, there really wasn't anything exciting at the conference, and so that was really the big takeaway. And so because of this, I think there were a number of other trials that now we've heard have are not moving ahead, that the mechanical turnback can be from MIEBO, so from an Academic research perspective,

除此之外，會議上真的沒有什麼令人興奮的事情，所以這真的是最大的收穫。因此，我認為現在我們聽說有許多其他試驗沒有取得進展，機械轉向可以透過 MIEBO 實現，所以從學術研究的角度來看，

I think that's going to be very positive for additional capacity for sites to be able to enrol a trial like ours, both those sites that that are currently activated and those sites that are coming on board for our trial.

我認為這將非常有利於增加站點參與像我們這樣的試驗的能力，包括目前已啟動的站點和即將參加我們試驗的站點。

Great. Thanks for taking our questions.

偉大的。感謝您回答我們的問題。

Matthew Caufield, H.C. Wainwright.

馬修·考菲爾德、H.C. 溫賴特。

Hi, good morning, guys. Thanks for the updates. For the preliminary top line in preeclampsia, expected in the second quarter, is there a meaningful threshold for impacting maternal blood pressure that would offer the best read through or de-risking for heading in?

大家好，早安。感謝您的更新。對於預計在第二季度出現的子癇前症的初步頂線數據，是否存在一個對孕婦血壓產生影響的有意義的閾值，從而提供最佳的解讀或降低風險？

Yeah, we're looking for is about a 10 to 20 drop in systolic pressure. We want to get systolic pressure down to about 140 so that they're safely in a good range, and we are also anticipating that on the safety side there won't be any evidence that DM199 passes the placental barrier and we're also looking at dilation of the intrauterine arteries using Doppler measurements to measure something called pulsativity index, which assesses resistance to blood flow in the uterine arteries.

是的，我們希望收縮壓下降 10% 到 20%。我們希望將收縮壓降至約 140，以便它們處於安全的良好範圍內，並且我們還預計在安全方面不會有任何證據表明 DM199 通過胎盤屏障，我們還在使用多普勒測量來觀察宮內動脈擴張，以測量所謂的脈動指數，該指數可評估子宮動脈的血流阻力。

We're looking for a lower pulsativity index, which suggests that there's lower resistance and better placental perfusion. So those are the three things that we're going to be looking at primarily in the Phase 1A trial. And if we see positive signals in those three areas, then that's a huge signal for us to move forward.

我們正在尋找較低的脈動指數，這表明阻力較低且胎盤灌注較好。所以這些就是我們在第 1A 期試驗中主要關注的三件事。如果我們在這三個領域看到積極的信號，那麼這對我們向前邁進來說是一個巨大的信號。

Great, very helpful. I appreciate that. And then just one final question from us, for ReMEDy2, with the inclusion of the thrombolytic non-responders, as the amended statistical analysis plan been finalized with the FDA at this stage?

非常好，很有幫助。我很感激。然後我們還有最後一個問題，對於 ReMEDy2，是否已將溶栓無反應者納入其中，因為修訂後的統計分析計劃是否已與 FDA 最終確定？

Yes, it has.

是的，確實如此。

Okay, great. Thank you, guys.

好的，太好了。謝謝你們。

Thank you so much. There are no further questions at this time. I would like to hand the call back over to Rick Pauls for closing remarks.

太感謝了。目前沒有其他問題。我想將電話轉回給 Rick Pauls 來做最後發言。

Thank you, Marissa. So, we'd like to thank everyone for joining us this morning and for your continued support. We are particularly excited about the momentum that we're building in both our stroke and preeclampsia programs as we advance DM199, a potentially transformative therapy for patients who do not have a treatment option today. The dedication of our team combined with your support to positioned us strongly for a very meaningful progress in 2025. We look forward to sharing updates with you soon.

謝謝你，瑪麗莎。因此，我們要感謝大家今天早上的參加以及你們一直以來的支持。隨著我們推進 DM199，我們對中風和子癇前症計畫所取得的進展感到特別興奮，DM199 是一種針對目前沒有治療選擇的患者的潛在變革性療法。我們團隊的奉獻精神加上您的支持，為我們在 2025 年取得非常有意義的進步奠定了堅實的基礎。我們期待很快與您分享最新消息。

Thank you again. With us, this concludes our call.

再次感謝您。我們的通話到此結束。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。