DiaMedica Therapeutics Inc (DMAC) 2021 Q4 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the DiaMedica Therapeutics Fourth Quarter 2021 Conference Call. An audio recording of the webcast would be available shortly after the call today on DiaMedica's website at www.diamedica.com in the Investor Relations section.

早安，女士們、先生們，歡迎參加 DiaMedica Therapeutics 2021 年第四季電話會議。今天電話會議後不久，將在 DiaMedica 網站 www.diamedica.com 的投資者關係部分提供網路廣播的錄音。

Before the company 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.

在該公司發表評論之前，請注意該公司將在今天的電話會議上發表前瞻性聲明。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。

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.

更多信息，包括可能導致實際結果與預測結果不同的因素，請參見昨天發布的公司新聞稿中標題為“有關前瞻性陳述的警示聲明說明”的部分以及DiaMedica 最新表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 15, 2022, and may no longer be accurate at the time of any replay or transcript rereading. 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今天（2022 年 3 月 15 日），在重播或重讀文字記錄時可能不再準確。 DiaMedica 不承擔任何更新其前瞻性聲明的責任。在準備好發言後，我們將開通電話提問。

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

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。保羅斯先生，您可以開始了。

Thank you, Julie. Good morning, everyone, and welcome to our year-end 2021 business update and earnings call. Yesterday after the market closed, we issued a press release summarizing our fourth quarter 2021 financial results and providing a general update. At the time, we also filed our quarterly report on Form 10-Q. Both documents can be found in the Investor Relations section of our website at diamedica.com.

謝謝你，朱莉。大家早安，歡迎參加我們的 2021 年底業務更新和財報電話會議。昨天收盤後，我們發布了一份新聞稿，總結了 2021 年第四季的財務表現並提供了整體更新。當時，我們也以 10-Q 表格形式提交了季度報告。這兩份文件均可在我們網站 diamedica.com 的投資者關係部分找到。

I'm joined this morning by our Chief Financial Officer, Scott Kellen; our Chief Medical Officer, Kirsten Gruis; our Chief Commercial Officer, Dominic Cundari; and our Senior VP of Clinical Operations, Harry Alcorn.

今天早上我們的財務長 Scott Kellen 也加入了我的行列。我們的首席醫療官 Kirsten Gruis；我們的首席商務長 Dominic Cundari；以及我們的臨床營運資深副總裁 Harry Alcorn。

I'd like to begin today with introducing you to our 2 newest members of our executive team. Kirsten is a board-certified neurologist experienced in both clinical medicine and drug development. She progressed and taught at the University of Michigan and the State University of New York in Syracuse. She began her work in drug development with Pfizer and has experience working with large and smaller organizations, including heading one of the neurological divisions at Roche and brings direct experience moving multiple compounds to the clinical and regulatory process in both the U.S. and Europe.

今天首先我想向您介紹我們執行團隊的兩位最新成員。克爾斯滕是一位經過委員會認證的神經科醫生，在臨床醫學和藥物開發方面經驗豐富。她在密西根大學和紐約州立大學錫拉丘茲分校升學並任教。她開始在輝瑞公司從事藥物開發工作，擁有與大型和小型組織合作的經驗，包括領導羅氏公司的一個神經科部門，並帶來了將多種化合物轉移到美國和歐洲的臨床和監管流程的直接經驗。

Dominic Cundari has over 30 years of commercial experience with Genentech, including managing the growth of the Activase or tPA franchise as it became the first approved therapeutic for treating acute ischemic stroke.

Dominic Cundari 在 Genentech 擁有 30 多年的商業經驗，包括管理 Activase 或 tPA 特許經營權的增長，因為它成為第一個被批准的治療急性缺血性中風的藥物。

Dom also provided the commercial leadership for LUCENTIS, the blockbuster macular degeneration treatment. We're extremely grateful to have both of these individuals join our team, and we thought that you may want to hear from them -- from these 2 and get their perspective in what attracted them to joining our team.

Dom 也為備受關注的黃斑部病變治療藥物 LUCENTIS 提供商業領導。我們非常感謝這兩個人加入我們的團隊，我們認為您可能想聽聽他們的意見——從這兩個人那裡了解他們的觀點，了解是什麼吸引他們加入我們的團隊。

So let's start with Dr. Gruis.

讓我們從格魯伊斯博士開始。

Thanks, Rick. So there were 3 main factors that attracted me to the company. First, the repeat findings from numerous randomized controlled trials described in the peer-reviewed medical literature from Asia consistently demonstrating clinical improvement in acute ischemic stroke patients receiving the human urinary derived form of KLK1. Second, the mechanism of action of KLK1 to selectively vasodilate arteries as this may improve collateral blood flow to the area of the brain with ischemia resulting in improved recovery from stroke. In addition, this improved collateral blood flow may also reduce the potential for stroke reoccurrence from a reocclusion of a blood vessel. Third, that the company took the time to match the PK profile of DM199, the recombinant form of KLK1, to the urinary form of KLK1 that has previously demonstrated in repeat trials, clinical improvement. This was to optimize the dosing regimen of DM199 in stroke clinical trials. So taken together, these 3 factors are what drew me to the company as they increase the probability of success of a clinical trial of recombinant DM199 in acute ischemic stroke.

謝謝，瑞克。所以有3個主要因素吸引我加入這家公司。首先，亞洲同行評審醫學文獻中描述的大量隨機對照試驗的重複結果一致證明，接受人類尿衍生形式 KLK1 的急性缺血性中風患者的臨床改善。其次，KLK1 選擇性舒張動脈的作用機制，因為這可以改善流向缺血腦部區域的側支血流，進而改善中風的恢復。此外，這種改善的側支血流還可以降低因血管再閉塞而再次發生中風的可能性。第三，該公司花時間將 KLK1 重組形式 DM199 的 PK 特性與先前在重複試驗中證明的 KLK1 尿液形式進行匹配，臨床改善。這是為了優化中風臨床試驗中 DM199 的給藥方案。綜上所述，這三個因素吸引了我來到這家公司，因為它們增加了重組 DM199 在急性缺血性中風中的臨床試驗的成功可能性。

Great. Thank you, Kirsten. We're very excited to have you join our team. Now let's hear from Dominic.

偉大的。謝謝你，克爾斯滕。我們非常高興您加入我們的團隊。現在讓我們聽聽多明尼克的說法。

Yes. Thanks, Rick. When I researched DiaMedica and DM199, my first impression was that DM199 is not incremental -- not an incremental therapeutic modality, but a treatment that can significantly advance stroke care for a large number of ischemic stroke patients.

是的。謝謝，瑞克。當我研究 DiaMedica 和 DM199 時，我的第一印像是 DM199 不是漸進式治療——不是一種增量治療方式，而是一種可以顯著促進大量缺血性中風患者的中風護理的治療方法。

Over the past couple of decades, my focus in acute ischemic stroke has been working with hospital neurologists on the front end with a 0 to 4.5-hour treatment window for TPA. Unfortunately, only about 1/3 of the acute ischemic stroke patients get to the hospital within this narrow treatment window. And of those, only about half are eligible for TPA.

在過去的幾十年裡，我對急性缺血性中風的關注重點一直是與醫院神經科醫生在前端合作，為 TPA 提供 0 至 4.5 小時的治療窗口。不幸的是，只有大約 1/3 的急性缺血性中風患者在這個狹窄的治療窗口內到達醫院。其中，只有大約一半有資格獲得 TPA。

So the net result is that only about 8% of all admitted stroke patients get TPA. Typically, a stroke patient will have a hospital stay of 5 or 6 days with physician monitoring and perhaps an additional look at CT or MRI and maybe an anticoagulant or an antiplatelet is added to the treatment regimen.

因此，最終結果是，所有入院的中風患者中只有約 8% 接受了 TPA。通常情況下，中風患者將住院 5 或 6 天，並由醫生監測，可能還會額外檢查 CT 或 MRI，並且可能會在治療方案中添加抗凝血劑或抗血小板藥物。

Now looking ahead, based on Phase II data, DM199 can potentially reduce visibility and reduce the likelihood of recurrent stroke. And with an expanded treatment window from 0 to 24 hours, annually, over 500,000 acute ischemic stroke patients can fall within this treatment window. So there is a significant opportunity to advance stroke care for a large number of patients during the recovery phase of stroke.

現在展望未來，根據 II 期數據，DM199 可能會降低能見度並降低中風復發的可能性。隨著治療窗口從 0 小時擴大到 24 小時，每年有超過 50 萬名急性缺血性中風患者可以進入此治療窗口。因此，在中風恢復階段，有一個重要的機會來推動對大量患者的中風護理。

I might add that the mode of action for DM199 is well explained and understood. Secondly, there are numerous clinical trials with human sourced KLK1, demonstrating safety and improved stroke recovery in terms of reducing disability and reducing stroke recurrence.

我想補充一點，DM199 的作用模式已被很好的解釋和理解。其次，大量的人源 KLK1 臨床試驗證明了其安全性，並在減少殘疾和減少中風復發方面改善了中風恢復。

I might add that a recombinant form of DM199 will assure purity of the product and abundant supply. And last, I believe that DM199 will be well received by the neurology customer base. Thanks, Rick.

我想補充一點，DM199 的重組形式將確保產品的純度和充足的供應。最後，我相信DM199將受到神經科客戶群的好評。謝謝，瑞克。

Thank you, Don. We're equally excited to have you joining our team. And ultimately, we feel the real winners here are going to be the patients. So now I'd like to provide an update on our lead program, our Phase II/III ReMEDy2 trial of DM199, in the treatment of acute ischemic stroke, referred to as AIS.

謝謝你，唐。我們同樣很高興您加入我們的團隊。最終，我們認為真正的贏家將是患者。現在我想介紹我們的主導計畫的最新情況，即 DM199 的 II/III 期 ReMEDy2 試驗，該試驗用於治療急性缺血性中風（簡稱 AIS）。

The design of the ReMEDy2 has some interesting and unique aspects. The trial is randomized placebo-controlled study that will enroll approximately 350 patients like clinical sites in the U.S. What is unique about the design is that we're planning to assess 2 separate independent primary endpoints with the same study population. These endpoints include an evaluation of stroke recoveries, can the patients return to normal physical function, so things like being able to eat, bathe, drive on their own, and the rate of recurrence of acute ischemic stroke in the 3 months following the initial stroke.

ReMEDy2 的設計有一些有趣且獨特的面向。該試驗是一項隨機安慰劑對照研究，將招募約 350 名患者，如美國的臨床中心。該設計的獨特之處在於，我們計劃對同一研究人群評估 2 個獨立的主要終點。這些終點包括對中風恢復情況的評估，患者能否恢復正常的身體功能，例如能夠吃飯、洗澡、獨立駕駛，以及初次中風後3個月內急性缺血性中風的複發率。

Each of these endpoints is clinically meaningful and could greatly benefit stroke patients as well as their families and caregivers. This also gives us 2 opportunities to achieve an improved outcome with the FDA. The adaptive study of -- design of the study is a second unique feature. For the study, adaptive refers to the interim analysis we are planning after approximately 40% or 140 patients have completed enrollments. The Data Safety Monitoring Board, or the DSMB, for the study will review the results from these patients to evaluate the effects that DM199 is having on stroke recoveries and the rate of recurrence. Based upon this evaluation, the DSMB will take action from stopping the study for futility or overwhelming efficacy, to continue the study as planned, or increasing the number of study participants.

這些終點中的每一個都具有臨床意義，並且可以使中風患者及其家人和照護者受益匪淺。這也為我們提供了 2 個機會來改善 FDA 的結果。研究設計的適應性研究是第二個獨特的特徵。對於這項研究，適應性是指我們計劃在大約 40% 或 140 名患者完成入組後進行中期分析。研究的資料安全監測委員會（DSMB）將審查這些患者的結果，以評估 DM199 對中風恢復和復發率的影響。根據此評估，DSMB 將採取行動，包括因無效或壓倒性療效而停止研究、按計劃繼續研究或增加研究參與者的數量。

The benefit here is having the ability to increase the sample size. If the actual benefit is looking like it's coming in below the planned benefit level, having the opportunity to increase the number of patients gives us the opportunity to ensure that we achieve statistically significant outcome and have a successful clinical trial.

這樣做的好處是能夠增加樣本量。如果實際效益看起來低於計劃的效益水平，那麼有機會增加患者數量，我們就有機會確保實現統計上顯著的結果並進行成功的臨床試驗。

Utilizing the adaptive trial design allows us to better manage the clinical risk, increase our chances for completing a successful trial. Note that we will be blinded to the results of this analysis and only know if and how the DSMB recommends that we move forward.

利用適應性試驗設計使我們能夠更好地管理臨床風險，增加成功完成試驗的機會。請注意，我們對該分析的結果視而不見，只知道 DSMB 是否以及如何建議我們繼續前進。

Let me also briefly highlight that DM199 received FDA Fast Track designation for the treatment of AIS last year. This is an important milestone and underscore the significant unmet medical need that exists among patients suffering from AIS, where there hasn't been a new or meaningful therapeutic advancement in over 25 years.

我還想簡單強調一下，DM199 去年獲得了 FDA 治療 AIS 的快速通道指定。這是一個重要的里程碑，強調了 AIS 患者中存在的重大未滿足的醫療需求，在超過 25 年的時間裡沒有新的或有意義的治療進展。

The Fast Track designation provides us with the opportunity for more frequent interactions with the FDA and may eventually qualify DM199 for accelerated and priority review. As an update on the sites. We have 10 sites now under contract. And adding the sites currently in startup phase, we have engaged with over 70% of our targeted numbers of sites for the trial. Startup sites represent sites that have been vetted, interested in participating and are proceeding towards activation to be able to enroll patients.

快速通道資格為我們提供了與 FDA 更頻繁互動的機會，並可能最終使 DM199 獲得加速和優先審查資格。作為網站上的更新。我們現在有 10 個簽訂合約的站點。再加上目前處於啟動階段的網站，我們已經與超過 70% 的目標網站進行了試驗。啟動站點代表已經過審查、有興趣參與並正在著手啟動以便能夠招募患者的站點。

Unfortunately, we can't control COVID, but our clinical team continues to work with members of our Scientific Advisory Board and other physicians in our network to reach out directly to the neurologists at key study sites to support making ReMEDy2 a priority study for their institutions.

不幸的是，我們無法控制新冠病毒，但我們的臨床團隊將繼續與我們的科學諮詢委員會成員和我們網絡中的其他醫生合作，直接聯繫關鍵研究地點的神經科醫生，以支持將ReMEDy2 作為其機構的優先研究。

While it's unfortunate that the startup process has been a little slow up to this point, we are encouraged by the fact that our issues have been COVID related and not related to concerns about DM199, or the study design. At the current rate of COVID infections and hospitalizations have rapidly been declining, we're optimistic that hospitals will be able to restore their research staffing.

雖然不幸的是，到目前為止啟動過程有點慢，但我們的問題與新冠病毒相關，而不是與 DM199 或研究設計的擔憂相關，這一事實令我們感到鼓舞。目前新冠病毒感染率和住院率正在迅速下降，我們對醫院能夠恢復研究人員配置感到樂觀。

We're also in the process of evaluating additional steps to potentially support site contracting and patient recruitment. We believe that we are well positioned to then engage them and advance this clinical trial.

我們也正在評估可能支援現場承包和患者招募的其他步驟。我們相信我們有能力與他們合作並推進這項臨床試驗。

In terms of our expected timing, as we have discussed, the ultimate timing for the completion of our interim analysis and the study itself will be driven by the rate at which our study sites are able to enroll patients. Our current plans are based upon a fairly conservative projected enrollment rates. We are more optimistic after the recent quick declines of COVID cases, as I mentioned.

就我們的預期時間而言，正如我們所討論的，完成中期分析和研究本身的最終時間將取決於我們的研究中心能夠招募患者的速度。我們目前的計劃是基於相當保守的預計入學率。正如我所提到的，最近新冠病例迅速下降後，我們變得更加樂觀。

We believe that the combination of our longer treatment window of 24 hours from stroke onset, combined with our safety profile and the potential to improve both stroke recovery and reduce the risk of stroke recurrence may drive a better enrollment rate. We will keep you updated as we get more clarity on both the site activation and enrollment rates as we hit milestones. I would like to also reiterate that the ReMEDy2 is our primary focus right now as we believe it has the fastest path to commercial approval.

我們相信，從中風發作起 24 小時的較長治療窗口，加上我們的安全性以及改善中風恢復和降低中風復發風險的潛力，可能會帶來更好的入組率。當我們達到里程碑時，我們會更清楚地了解網站啟動率和註冊率，我們將隨時向您通報最新情況。我還想重申，ReMEDy2 是我們目前的主要關注點，因為我們相信它擁有最快的商業批准途徑。

Turning to our REDUX, our Phase II CKD program. We recently completed enrollment and are working through the final patient follow-ups and cleaning the study data to prepare for the final analysis and reporting. As most of you know, REDUX is a basket or a signaling study in which we're evaluating 3 different causes of chronic kidney disease and 2 different dose levels of DM199, over approximately a 3-month treatment period.

轉向我們的 REDUX，我們的第二階段 CKD 計劃。我們最近完成了入組工作，正在進行最終的患者追蹤並清理研究數據，為最終分析和報告做好準備。正如大多數人所知，REDUX 是一個籃子或訊號研究，我們在大約 3 個月的治療期內評估慢性腎病的 3 種不同原因和 DM199 的 2 種不同劑量水平。

Currently, the key takeaway from REDUX is that the CKD represents an attractive development opportunity for DM199. We believe that the study is directing us towards targeting subgroup of hypertensive African-Americans and/or IG nephropathy patients, who have moderate to severe kidney disease. Patients whom both have improving kidney function and controlling blood pressure could greatly improve their quality of life.

目前，REDUX 的主要收穫是 CKD 為 DM199 提供了一個有吸引力的開發機會。我們相信，這項研究引導我們針對患有中度至重度腎臟疾病的高血壓非裔美國人和/或 IG 腎臟病患者亞群。改善腎功能和控制血壓的患者可以大大提高他們的生活品質。

We look forward to updating you on the next steps after we complete the final analysis of the REDUX data and in terms of the next steps and potentially discussing our results with the FDA.

我們期待在完成 REDUX 數據的最終分析後向您通報後續步驟的最新情況，並可能與 FDA 討論我們的結果。

Now I'll ask Scott Kellen to take us through the financial results for our fourth quarter.

現在我請史考特‧凱倫向我們介紹第四季的財務表現。

Thank you, Rick. Good morning, everyone. As Rick mentioned, we did announce our full year '21 financial results and filed our annual report on Form 10-K yesterday after the markets closed. These documents are both available on either the DiaMedica or the SEC website.

謝謝你，瑞克。大家，早安。正如 Rick 所提到的，我們確實公佈了 21 年全年財務業績，並在昨天市場收盤後提交了 10-K 表格年度報告。這些文件均可在 DiaMedica 或 SEC 網站上取得。

Now going through the financials. Our net loss for the full year of '21 was $13.6 million or $0.65 per share, which compares with our prior year net loss of $12.3 million or $0.78 per share. Our cash position remains strong with $45.1 million of cash, cash equivalents and marketable securities as of December 31, 2021, which is up from $27.5 million at the end of the prior year. We believe our current cash will support the clinical development of DM199 and fund our operations into early 2024.

現在正在檢查財務狀況。我們 21 年全年的淨虧損為 1,360 萬美元，即每股 0.65 美元，而前一年的淨虧損為 1,230 萬美元，即每股 0.78 美元。截至 2021 年 12 月 31 日，我們的現金狀況依然強勁，現金、現金等價物及有價證券為 4,510 萬美元，高於上年末的 2,750 萬美元。我們相信，我們目前的現金將支持 DM199 的臨床開發，並為我們的營運提供資金直至 2024 年初。

Our research and development expenses increased slightly to $8.8 million for the year ended December 31, 2021, up from $8.2 million for the full year of 2020. This increase was primarily due to a combination of the additional costs incurred for our Phase II/III ReMEDy2 trial and increased personnel costs associated with adding staff to support our expanding clinical programs.

截至 2021 年 12 月 31 日止年度，我們的研發費用小幅增加至 880 萬美元，高於 2020 年全年的 820 萬美元。這一增長主要是由於我們的 II/III 期 ReMEDy2 產生的額外成本試驗以及與增加人員以支持我們不斷擴大的臨床項目相關的人員成本增加。

This increase was partially offset by decreased costs incurred for our earlier ReMEDy1 Phase II AIS study, which completed during 2020 and then decreased cost for the REDUX trial as the number of enrollments in the trial declined through 2021 as the study neared completion.

這一增長被我們早期的 ReMEDy1 II 期 AIS 研究產生的成本下降所部分抵消，該研究於 2020 年完成，然後隨著研究接近完成，REDUX 試驗的入組人數在 2021 年下降，因此成本下降。

Our general and administrative expenses were $4.9 million and $4.5 million for the full fiscal years 2021 and 2020, respectively. The increase was due to a number of factors, including increased costs associated with professional services, the payment to Catalent of a milestone obligation under our technology license agreement with Catalent, increased directors' and officers' liability insurance costs and increased personnel costs to support the company's R&D operations. These increases were partially offset by a reduction in our noncash share-based compensation costs.

2021 年和 2020 年整個財政年度的一般費用和管理費用分別為 490 萬美元和 450 萬美元。這一增長是由於多種因素造成的，包括與專業服務相關的成本增加、根據我們與康泰倫特的技術許可協議向康泰倫特支付里程碑式的義務、董事和管理人員責任保險成本的增加以及支持康泰倫特的人員成本的增加。公司的研發業務。這些成長被我們非現金股票薪酬成本的減少部分抵銷。

Turning to the cash flows. Our net cash used in operating activities for the year ended December 31, 2021, was $12.3 million compared to $9.2 million for the full year 2020. This increase relates primarily to our increased net loss in 2021 and partially offset by share-based compensation and the effects of changes in operating assets and liabilities. And importantly, as I mentioned earlier, we believe our current cash will support the clinical development of DM199 and our operations into early 2024.

轉向現金流。截至2021 年12 月31 日止的年度，我們用於經營活動的淨現金為1,230 萬美元，而2020 年全年為920 萬美元。這一增長主要與我們2021 年淨虧損的增加有關，部分被股權激勵和經營資產和負債變化的影響。重要的是，正如我之前提到的，我們相信我們目前的現金將支持 DM199 的臨床開發和我們到 2024 年初的營運。

Now let me turn the call back over to Rick.

現在讓我把電話轉回給里克。

Thank you, Scott. As you can see, we've had a very productive 2021, which is continuing into 2022, including significant progress with DM199, our clinical trials and building our team. And with our strong balance sheet, we are well positioned to continue to execute on our plans we have reviewed for you today.

謝謝你，斯科特。正如您所看到的，我們的 2021 年非常富有成效，並將持續到 2022 年，包括 DM199、我們的臨床試驗和團隊建立的重大進展。憑藉我們強大的資產負債表，我們有能力繼續執行我們今天為您審查的計劃。

With that, we'd like to open the call for questions. Operator, could you please introduce the first analyst?

至此，我們想開始提問。接線員，可以介紹一下第一位分析師嗎？

(Operator Instructions) Your first question comes from Alex Nowak from Craig-Hallum Capital Group.

（操作員說明）您的第一個問題來自 Craig-Hallum Capital Group 的 Alex Nowak。

Kirsten, I appreciate the intro and kind of your background on what attracted you to the company. Just curious, beyond the pivotal stroke study that's going on, can you walk through some of the additional studies, lab or bench data that you're looking to generate here over the coming months to years to help position the company's product of DM199?

克斯汀（Kirsten），我很欣賞您的介紹以及吸引您加入公司的背景。只是好奇，除了正在進行的關鍵中風研究之外，您能否介紹一下您希望在未來幾個月到幾年內生成的一些額外研究、實驗室或實驗數據，以幫助定位該公司的 DM199 產品？

Yes, absolutely. Maybe I'll take this. So right now, really, our focus with our clinical team is on the ReMEDy2 trial. And so while we're working on that, we are starting to -- looking at what next steps, potential steps are for the kidney program, but we just want to make sure that we're very focused here right now on the stroke pivotal trial.

是的，一點沒錯。也許我會接受這個。所以現在，我們臨床團隊的重點其實是 ReMEDy2 試驗。因此，在我們致力於此的同時，我們開始研究腎臟計劃的後續步驟和潛在步驟，但我們只是想確保我們現在非常關注中風關鍵問題審判。

Okay. Understood. And maybe refresh us -- and this is, I guess, a broader question, refresh us the regulatory landscape for chronic kidney disease in the U.S. now because we saw the CRL from Reata recently. I mean they were kind of paving the path forward. So does the broader CKD space, do we need -- I mean, do we know necessarily the path necessary to get through FDA approval at this time? Do we need to reset in which kidney metrics we need to focus on like UACR, eGFR? Just any thoughts there?

好的。明白了。也許會讓我們耳目一新——我想這是一個更廣泛的問題，讓我們耳目一新地了解美國慢性腎臟病的監管環境，因為我們最近看到了 Reata 的 CRL。我的意思是他們正在為前進鋪平道路。那麼，我們是否需要更廣泛的 CKD 空間——我的意思是，我們是否知道此時獲得 FDA 批准所需的途徑？我們是否需要重新設定需要關注的腎臟指標，例如 UACR、eGFR？只是有什麼想法嗎？

Yes. That's a really good question, Alex. So if we look in 2019, there was new guidance from a working group with the National Kidney Foundation, the FDA and EMA that really is looking at surrogate endpoints for approval. And so our understanding, in particular, when we're looking at rare forms of kidney disease is that there's the potential to have conditional approval based upon UACR, the albuminuria levels, and guidelines of ideally over 30% reduction over 6-plus months for the conditional approval and then full approval over 2 years based upon a slowing in the rate of decline of eGFR. And I think we can look at the recent approval of [Callidus] based upon their UACR just going back to a few months.

是的。這是一個非常好的問題，亞歷克斯。因此，如果我們展望 2019 年，就會發現國家腎臟基金會、FDA 和 EMA 的一個工作小組發布了新指南，該指南確實正在研究替代終點以供批准。因此，我們的理解是，特別是當我們研究罕見形式的腎臟疾病時，有可能根據 UACR、蛋白尿水平以及理想情況下在 6 個多月內減少 30% 以上的指導方針獲得有條件批准。根據eGFR 下降速度的減緩，有條件批准，然後在2 年內完全批准。我認為我們可以根據幾個月前的 UACR 查看 [Callidus] 最近的批准情況。

So I think we're very encouraged in terms of the potential regulatory path here for chronic kidney disease. And so what we're currently looking at, we have a few different potential pathways to move forward in terms of kidney disease, focusing more so on the hypertensive African-Americans and maybe a subgroup of these patients and/or IgA nephropathy.

因此，我認為我們對慢性腎臟病的潛在監管途徑感到非常鼓舞。因此，我們目前正在研究的是，我們有一些不同的潛在途徑可以在腎臟疾病方面取得進展，更專注於高血壓非裔美國人，也許還有這些患者和/或 IgA 腎病的一個亞群。

So again, we want to look a little more carefully at our data to really see which cause of kidney disease we think would be the best fit for our therapy and also in the context of the competitive landscape.

因此，我們希望更仔細地研究我們的數據，以真正了解我們認為哪種腎臟疾病的原因最適合我們的治療，並且在競爭格局的背景下。

So we're very excited about the potential, and we just want to make sure that before we come out and provide an update to the market, we have a very clear indication of what that cause and what that regulatory path will be going forward.

因此，我們對這種潛力感到非常興奮，我們只是想確保在向市場提供最新資訊之前，我們已經非常清楚地表明了原因以及監管路徑將如何發展。

Yes. Understood. It makes total sense. And then just a clarification question around the enrollment. So you said 10 sites were under contract. Are those the number of sites that are actively enrolling patients? And if not, what is that number of actively enrolling? And then how long to convert the 70% of targeted sites under discussion to active enrollment just based on where things are trending in the last month or so?

是的。明白了。這是完全有道理的。然後是關於註冊的澄清問題。所以你說有 10 個站點簽訂了合約。正在積極招募病患的站點數是多少？如果沒有，那麼積極註冊的人數是多少？然後，僅根據上個月左右的趨勢，將 70% 正在討論的目標網站轉變為主動註冊需要多長時間？

Yes. So actually -- we can actually follow live on ClinicalTrials.gov. Usually it's a couple of weeks late. But we've got 4 or 5 sites right now that are actively recruiting. Our intent here is to provide everyone with an update on enrollment milestones along the way. And just with a little bit of additional color here.

是的。所以實際上 - 我們實際上可以在 ClinicalTrials.gov 上進行即時追蹤。通常會晚幾個星期。但我們現在有 4 或 5 個站點正在積極招募。我們的目的是為每個人提供註冊里程碑的最新資訊。這裡只是添加了一點額外的顏色。

So with the COVID variant, both the delta and the Omicron surging in the second half of the year, there was some challenges with the sites that were shifting their staff away from research. But what we can share with you this time is that we're not having any trouble getting interest from the sites that have the research teams in place.

因此，隨著新冠病毒的變種，Delta 和 Omicron 都在下半年激增，那些將員工從研究領域轉移出去的網站面臨一些挑戰。但這次我們可以與您分享的是，我們在吸引擁有研究團隊的網站的興趣方面沒有任何困難。

Once committed, they've been steadily moving this process forward. Combining that with the response that we got at the recent International Stroke Conference, we don't have concerns about the interest. It's really about now converting these sites over. So we're talking over 50 sites in total here that are contracted and/or going through the process.

一旦做出承諾，他們就會穩定地推動這項進程。結合我們在最近的國際中風會議上得到的回應，我們並不擔心這種興趣。現在真正需要改變的是這些網站。因此，我們在這裡討論的總共有 50 多個已簽約和/或正在經歷流程的網站。

And so the other piece to this that we're also kind of refocusing is really on focusing on those sites that we believe can enroll greater than one patient per month. So really focusing on those sites, we think, will be the optimal enrollers and we're still targeting the first half of 2023 for the interim analysis.

因此，我們也重新關注的另一件事實際上是專注於那些我們認為每月可以招募超過一名患者的網站。因此，我們認為，真正關注這些網站將是最佳的註冊者，我們仍將目標定在 2023 年上半年進行中期分析。

Your next question comes from Frank Brisebois from Oppenheimer.

您的下一個問題來自奧本海默的弗蘭克·布里斯博伊斯。

This is Daniel on behalf of Frank Brisebois. Just a quick one. Could you add some more color on the importance of the interim look, particularly in terms of efficacy? And you already talked about the enrollment rate. So just wondering how the enrollment is going on given that you have this sweet spot of patients who need to have a small blood vessel occlusion enrollment within 24 hours. Just to talk about the -- some color on the interim look, that would be great.

我是丹尼爾，代表弗蘭克·布里斯博伊斯。只是快一點。您能否進一步說明臨時外觀的重要性，特別是在功效方面？您已經談到了入學率。因此，我想知道登記的進展如何，因為您有這樣的最佳時機，需要在 24 小時內進行小血管閉塞登記的患者。只是談談臨時造型上的一些顏色，那就太好了。

Sure. Yes. So at the interim analysis, so after 40% of the patients have completed therapy, the data safety monitoring board will review the results and make a recommendation to us on how to proceed. And there's really 3 different options -- 3 different scenarios here that we anticipate. So the first is to continue the study as planned. Second is to increase the number of patients. And then third will be stopping the study for either overwhelming efficacy or for a lack of efficacy. So the premise here is that DiaMedica will be blinded, but it will be an opportunity really here to, most importantly, to increase the study size, if needed, to potentially reach statistical significance.

當然。是的。因此，在中期分析中，40％的患者完成治療後，資料安全監測委員會將審查結果並向我們提出如何繼續的建議。實際上有 3 種不同的選擇——我們預計有 3 種不同的場景。所以首先是按計劃繼續研究。二是增加就診人數。第三，由於療效壓倒性或缺乏療效而停止研究。因此，這裡的前提是 DiaMedica 將被蒙蔽，但這將是一個真正的機會，最重要的是，如果需要的話，可以增加研究規模，以達到統計顯著性。

Great. That makes sense. And just one more question on the REDUX side of things. Are you sharing anything on when we can expect to see the final CKD data? And as a related, are you planning to move forward with the program yourself? Or is there any thoughts about partnership on that end?

偉大的。這就說得通了。還有一個關於 REDUX 方面的問題。您是否可以分享有關我們何時可以看到最終 CKD 數據的資訊？相關人士，您打算親自推動該計劃嗎？或是在這方面有什麼關於合作的想法嗎？

Yes. So later this year, we're not anticipating any material difference from what's been reported. And in particular, you can look at the ASN poster presentation we had back in November. And right now, we're exploring a number of different options and the potential for our partnership is one of the pieces that we are looking at as the potential next steps.

是的。因此，今年晚些時候，我們預計不會與報告的內容有任何實質差異。特別是，您可以查看我們 11 月的 ASN 海報演示。目前，我們正在探索多種不同的選擇，我們合作夥伴關係的潛力是我們正在考慮的下一步潛在步驟之一。

I think what we want to be very careful about here is we don't want to do anything that will jeopardize our capital use funding our stroke program to getting to that interim and then to still have a runway post interim, which is most important in terms of our capital budget right now.

我認為我們在這裡要非常小心的是，我們不想做任何會危及我們為中風計劃提供資金的資本使用的事情，以達到過渡期，然後在過渡期後仍然有一個跑道，這是最重要的我們現在的資本預算條款。

And there are no further questions at this time. I will turn the call back over to Rick Pauls, CEO, for closing remarks.

目前沒有其他問題。我將把電話轉回首席執行官里克·保羅斯 (Rick Pauls) 發表結束語。

All right. Again, we like to thank everyone for joining us this morning. We appreciate your interest in DiaMedica and your continued support. With this, we conclude our call.

好的。我們再次感謝大家今天早上加入我們。我們感謝您對 DiaMedica 的興趣和持續的支持。至此，我們的通話結束。

This concludes today's conference call. You may now disconnect.

今天的電話會議到此結束。您現在可以斷開連線。