DiaMedica Therapeutics Inc (DMAC) 2024 Q3 法說會逐字稿

(Technical difficulty)

（技術難度）

That thrombolytics have a very short half-life, approximately 24 minutes and are therefore cleared from the body rapidly. These agents undergo seven half lives in less than three hours and are effectively cleared from the patient's system three hours after dosing. So, if a patient is presenting with persistent moderate to severe stroke severity, several hours after TPA is cleared from the system, it indicates that thrombolytics didn't meaningfully correct the neurological deficit.

溶栓劑的半衰期很短，大約為 24 分鐘，因此會迅速從體內清除。這些藥物在不到三小時的時間內經歷七個半衰期，並在服藥三小時後從患者體內有效清除。因此，如果患者在 TPA 從系統中清除數小時後仍出現持續中度至重度中風，則表示血栓溶解劑無法有效矯正神經功能缺損。

We colloquially refer to this type of patient as the TPA or thrombolytic non responder. We want to capture this type of patient because we anticipate they will have a low placebo response rate and there is potential for a significant treatment effect when compared with the DM199 therapy.

我們通俗地將這種類型的患者稱為 TPA 或溶栓無反應者。我們希望吸引這類患者，因為我們預期他們的安慰劑反應率較低，而且與 DM199 療法相比，治療效果可能會更顯著。

On the right side of the slide, you can see the data from our remedy one study in participants treated with TPA prior to enrollment. As you can see in the placebo group, the response rate was zero, which we believe affirms that these participants were TPA non responders. Conversely in the DM199 arm, the response rate was 25%. This 25% improvement versus placebo was actually the highest performance improvement among all subgroups studied in the remedy one trial.

在投影片的右側，您可以看到我們對在入組前接受 TPA 治療的參與者進行的第一項療法研究的數據。正如您在安慰劑組中所看到的，反應率為零，我們相信這證實了這些參與者對 TPA 無反應。相反，在 DM199 組中，回應率為 25%。與安慰劑相比，這 25% 的改善實際上是治療第一期試驗中研究的所有亞組中最高的表現改善。

I also want to note that the primary reason we didn't initially include TPA non responders in the remedy two study initially was to the significant difference in outcomes based upon how soon after a stroke, the patient receives TPA, those receiving TPA at one hour, post stroke have been shown to do much better than those receiving TPA four hours post stroke.

我還想指出的是，我們最初沒有將 TPA 無反應者納入第二種治療方法的研究的主要原因是，根據中風後患者接受 TPA 的時間長短，結果存在顯著差異。

At the time, DiaMedica didn't want to introduce this potential variability into the study and the clinical risk of an imbalance of TPA patients in favor of the placebo arm. However, upon considering the remedy, one results, if we properly define the thrombolytic non responder, I believe that we can eliminate this variability. Risk.

當時，DiaMedica 不想將這種潛在的變異性引入研究中，也不想引入 TPA 患者偏向安慰劑組的臨床風險。然而，在考慮治療方法後，如果我們正確定義對溶栓無反應者，我相信我們可以消除這種差異。風險。

Turning to slide four, here are the details of the inclusion criteria related to TPA non responders. We've spent countless hours with our scientific advisory board and leading vascular neurologists who consult for DiaMedica to properly define the inclusion criteria which are listed on this slide.

翻到第四張投影片，這是與 TPA 無反應者相關的納入標準的詳細資訊。我們花了無數的時間與我們的科學顧問委員會和為 DiaMedica 提供諮詢的領先的血管神經病學家一起正確地定義這張幻燈片上列出的納入標準。

After discussions with our scientific advisory board and stroke neurologists in our trial, we believe the best time to assess when a patient is a non-responder is six hours after thrombolytics have been administered. If you intervene earlier. For example, at four hours, there is a greater risk that the patient is a delayed responder. If you wait until hour 12, there is a risk of more brain tissue dying from the impaired blood flow. We think six hours strikes the right balance and recall in our prior remedy one study; DM199 was administered on average 13.5 hours after TPA. If we can actually get to patients more quickly, we have the potential to improve upon the treatment effects we already saw in the remedy one trial.

在我們的試驗中，經過與我們的科學顧問委員會和中風神經病學家的討論，我們認為評估患者對藥物無反應的最佳時間是注射溶栓劑六小時後。如果你早點介入。例如，當睡眠時間達到四小時時，患者出現延遲反應的風險就會更大。如果等到第 12 小時，就會有更多的腦組織因血流受阻而死亡。我們認為六小時達到了最佳平衡，並回憶起我們先前的一項治療研究； DM199 平均在 TPA 後 13.5 小時給藥。如果我們實際上能夠更快地接觸到患者，我們就有可能改善我們在第一次治療試驗中已經看到的治療效果。

The second point that I want to emphasize is that at or after that six-hour mark, the patient must be reevaluated. The neurological deficit must be persistent and fall within the same stroke severity range as non TPA patients, meaning an NIHSS score between 5 and 15. And when we say persistent neurological deficit, we mean that the patient cannot have experienced a four point or better improvement in their NIHSS score following thrombolytic treatment, we do not want patients to still fall within the NIHSS range but are on a trajectory to recover.

我想強調的第二點是，在六小時或之後，必須對患者進行重新評估。神經功能缺損必須是持續性的，並且屬於與非 TPA 患者相同的中風嚴重程度範圍，即 NIHSS 評分在 5 到 15 之間。當我們說持續性神經功能缺損時，我們的意思是患者在接受溶栓治療後，NIHSS 評分不可能有 4 分或更好的改善，我們不希望患者仍然處於 NIHSS 範圍內，但處於康復的軌道上。

And finally, the patient must be re scanned to rule out worsening as a result of any hemorrhagic transformation that may have been caused by the TPA. And the patient must meet all other criteria as non TPA patients. For example, being treated within the same 24-hour window from stroke symptom onset.

最後，必須對患者重新進行掃描，以排除 TPA 可能導致的出血性轉化而導致的病情惡化。且患者必須滿足非TPA患者的所有其他標準。例如，在中風症狀出現後的 24 小時內接受治療。

With this new criterion we think we've struck the right balance to include a patient population with a significant unmet need and that we anticipate we will respond favorably to M199.

我們認為，透過這項新標準，我們已經取得了適當的平衡，涵蓋了具有重大未滿足需求的患者群體，我們預計 M199 將獲得積極的反應。

Turning to slide 5. The other key update relates to the size of the interim analysis. Over the past 20 years, I've worked extensively with several leaders in statistical analysis for my studies whom I've had review our statistical analysis plan based upon the feedback and the potential reduction in the overall trial sample size. We made the decision to perform the interim analysis after enrolling 200 patients, an increase from the previously planned 144 participants.

翻到幻燈片 5。另一個重要更新與中期分析的規模有關。在過去的 20 年裡，我與我的研究中的幾位統計分析領導者進行了廣泛的合作，他們根據反饋和整體試驗樣本量的潛在減少情況審查了我們的統計分析計劃。我們決定在招募 200 名患者後進行中期分析，人數比先前規劃的 144 名有所增加。

Here on slide 6 is a very potent demonstration of why we don't want to be undersized at the interim analysis. This is an actual simulation from the model comparing final sample size estimates based upon enrolling 144 and 200 patients at interim. For trial integrity purposes, we can't disclose the actual treatment response and placebo response. But in the example, provided the values are identical and the only difference is the interim sample size.

投影片 6 非常有力地說明了為什麼我們不希望在中期分析時規模太小。這是透過模型進行的實際模擬，比較了分別招募 144 名和 200 名患者的最終樣本量估計值。為了確保試驗的完整性，我們不能透露實際的治療反應和安慰劑反應。但在範例中，假設值相同，唯一的差異是中期樣本大小。

As you can see in this scenario at 144 participants, the sample size re-estimate is 485 participants. Whereas at 200 it is 339 participants. I want to reiterate this is an actual simulation in the model driving our statistical analysis plan. From a cost standpoint this kind of difference could translate into a savings for DiaMedica of $10 million or more. We believe this change has the potential to accelerate completion of the overall study, even though it will delay receipt of our interim analysis results.

正如您所看到的，在這個場景中，參與者有 144 名，樣本量重新估計為 485 名參與者。而 200 時則有 339 位參與者。我想重申，這是我們統計分析計畫模型中的實際模擬。從成本角度來看，這種差異可以為 DiaMedica 節省 1000 萬美元甚至更多。我們相信，這項變更有可能加速整個研究的完成，即使它會延遲我們收到中期分析結果。

The effects on timing of our interim analysis will hopefully be partially offset by expanding our inclusion criteria and including thrombolytic non responder patients. Previously, we were anticipating, our interim analysis would be available in the summer of 2025 and now we expect it quarter 4, 2025. We believe that we are adequately financed through the interim analysis.

希望透過擴大納入標準並納入對溶栓無反應的患者，可以部分抵消對中期分析時間的影響。此前，我們預計我們的中期分析將於 2025 年夏季發布，現在我們預計它將在 2025 年第 4 季發布。我們相信，透過中期分析，我們已經獲得了足夠的資金。

Turning to slide 6, I would reiterate that we firmly believe that the protocol updates will accelerate enrollment rates with the addition of a subgroup of stroke patients that have the potential to be high responders to DM199 therapy as well as improving the potential commercial value of DM199. Further that with the new statistical analysis plan, we have the best potential for clinical success with the smallest possible studies.

轉到第 6 張投影片，我想重申，我們堅信協議更新將加速入組率，增加一組可能對 DM199 療法有高反應的中風患者，並提高 DM199 的潛在商業價值。此外，透過新的統計分析計劃，我們可以透過最小規模的研究獲得最大的臨床成功潛力。

I will now turn the call back over to Greg.

我現在將電話轉回給格雷格。

Thank you, Anne. Our focus with respect to the remedy two trial remains centered on continuing to build momentum with high quality research Institutions. Wave update as of today, we have the majority of our 15 priority study sites have been activated.

謝謝你，安妮。我們對第二種療法試驗的關注重點仍然是繼續與高品質研究機構合作，創造發展勢頭。截至今日的 Wave 更新，我們的 15 個優先研究站點中的大多數都已經啟動。

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

現在，我想將電話交給 Scott Kellen 來回顧本季的財務結果。

Thanks, Rick, and good morning, everyone, and thank you for joining us on today's call. Starting with our financial position, our September 30, 2024, combined cash, cash equivalents and investments balance is $50.2 million down from $52.9 million as of December 31, 2023.

謝謝，里克，大家早上好，謝謝您參加今天的電話會議。從我們的財務狀況開始，截至 2024 年 9 月 30 日，我們的現金、現金等價物和投資餘額合計為 5,020 萬美元，低於 2023 年 12 月 31 日的 5,290 萬美元。

Net cash used in operating activities for the 9 months ended September 30, 2024, was $15.6 million compared to $14.9 million in the same period of the prior year. The increase in cash used in operating activities resulted primarily from the combination of our increased net loss and the advance of deposit funds to vendors supporting the ReMEDy2 clinical trial during the current year period.

截至 2024 年 9 月 30 日的 9 個月的營業活動淨現金流為 1,560 萬美元，而去年同期為 1,490 萬美元。經營活動所用現金增加主要是由於本年度期間我們的淨虧損增加和向支持 ReMEDy2 臨床試驗的供應商預付的押金所致。

These increases were partially offset by changes in operating assets and liabilities during the current year period and we believe that our current cash and investments provides us a runway to Q3 of 2026. Our research and development expenses increased to $5 million for the 3 months ended September 30, 2024, up from $3.3 million in the prior year period. R&D expenses increased to $12.6 million for the 9 months ended September 30, 2024, compared to $9.4 million for the 9 months ended September 30, 2023.

這些成長被本年度期間經營資產和負債的變化部分抵消，我們相信，目前的現金和投資為我們提供了通往 2026 年第三季的跑道。截至 2024 年 9 月 30 日的 3 個月，我們的研發費用從去年同期的 330 萬美元增加至 500 萬美元。截至 2024 年 9 月 30 日的 9 個月的研發費用增加至 1,260 萬美元，而截至 2023 年 9 月 30 日的 9 個月的研發費用為 940 萬美元。

These increases are due primarily to cost increases resulting from the continuation of our ReMEDy2 clinical trial, the expansion of our clinical team and increased manufacturing development activity. These increases were partially offset by cost reductions related to clinical trial work completed in 2023, including our Phase Ic and REDUX trials, and the completion in 2023 of the in-use study work performed to address the prior clinical hold on the ReMEDy2 trial. We expect R&D expenses to increase moderately relative to recent prior periods, as we globally expand the ReMEDy2 trial site activations and participant enrollments continue.

這些成長主要是由於我們 ReMEDy2 臨床試驗的持續、臨床團隊的擴大以及製造開發活動的增加所導致的成本增加。這些成長部分被 2023 年完成的臨床試驗工作（包括我們的 Ic 期和 REDUX 試驗）以及 2023 年完成的為解決 ReMEDy2 試驗先前的臨床暫停而進行的使用中研究工作相關的成本減少所抵消。隨著我們在全球範圍內擴大 ReMEDy2 試驗站點的激活範圍以及參與者的持續招募，我們預計研發費用將相對近期適度增加。

Our general and administrative expenses were $1.9 million for each of the 3 months ended September 30, 2024, and 2023. G&A expenses were $5.7 million for the 9 months ended September 30, 2024, down from $6 million for the 9 months ended September 30, 2023. The decrease for the 9-month comparison resulted from the combination of reductions in the cost of directors' and officers' liability insurance premiums and decreased legal fees incurred in connection with our lawsuit against PRA Netherlands.

截至 2024 年 9 月 30 日及 2023 年 9 月 30 日的三個月內，我們的一般及行政費用均為 190 萬美元。截至 2024 年 9 月 30 日的 9 個月的 G&A 費用為 570 萬美元，低於截至 2023 年 9 月 30 日的 9 個月的 600 萬美元。前九個月的下降是由於董事和高階主管責任保險費用減少，以及我們與 PRA Dutch 的訴訟相關的法律費用減少。

These decreases were partially offset by increased personnel costs incurred in conjunction with expanding our team and increased noncash share-based compensation costs. We expect G&A expenses to remain steady as compared to recent prior periods. Other income net was $616,000 and $1.7 million for the 3 and 9 months ended September 30, 2024, respectively, compared to $693,000 and $1.2 million for the 3 and 9 month periods ended September 30, 2023, respectively.

這些減少部分被擴大團隊而產生的人員成本增加以及非現金股權激勵成本增加所抵消。我們預計，與近期相比，一般及行政開支將保持穩定。截至 2024 年 9 月 30 日的 3 個月和 9 個月的其他收入淨額分別為 616,000 美元和 170 萬美元，而截至 2023 年 9 月 30 日的 3 個月和 9 個月的其他收入淨額分別為 693,000 美元和 1200 萬美元。

The increase for the 9-month comparison was driven by increased interest income recognized during the current year period, related to higher marketable securities balances during the current year period as compared to the same period in the prior year.

前九個月的增幅是由於本年度確認的利息收入增加，這與本年度有價證券餘額較去年同期增加有關。

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

現在，請允許我請接線員開通問答熱線。

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session.(Operator instruction). Your first question comes from Thomas Flaten with Lake Street.

謝謝。女士們、先生們，我們現在開始問答環節。您的第一個問題來自 Lake Street 的 Thomas Flaten。

Good morning. I appreciate you taking the questions, Marian. Just sticking with remedy two. What was the original prompt for, for reevaluating the protocol and statistical analysis plan? Was it, was it just to see higher enrollment rates or was there some other prompt for that entire discussion that led to these changes?

早安.感謝您回答這些問題，瑪麗安。只需堅持第二種補救措施。重新評估協議和統計分析計劃的最初提示是什麼？是僅僅為了提高入學率，還是整個討論中還有其他因素促使了這些變化？

It was really a combination of wanting to simulate enrollment but also extensive discussions that we had with our SAB and our KOL experts that we've been working with. They really were very excited to see what would happen with the patients who had received thrombolytic therapy but were non-responders. We worked with statistical experts who said that they thought that it would be important to have at least half of the patients enrolled before doing a high quality basian sample size adjustment. So we made the adjustment there based on a lot of statistical input.

這實際上是想要模擬註冊，同時也是我們與 SAB 和我們一直合作的 KOL 專家進行廣泛討論的結合。他們確實非常興奮地想看看那些接受溶栓治療但沒有反應的患者會發生什麼事。我們與統計專家合作，他們說他們認為在進行高品質的基礎樣本量調整之前讓至少一半的患者入組非常重要。因此我們根據大量的統計數據做出了調整。

Got it. And then just a, I guess a somewhat technical question at what point will patients now be randomized? Particularly those that are TPA failures because you want to balance those patients across the two arms and you won't really know if they're failures, if you randomize them prior to getting TPA. So, could you walk us through kind of the nitty gritty on that?

知道了。然後，我想這是一個有點技術性的問題，什麼時候病人會被隨機分配？特別是那些 TPA 失敗的患者，因為您想要在兩個組之間平衡這些患者，並且如果您在進行 TPA 之前將他們隨機化，您將無法真正知道他們是否失敗。那麼，您能向我們詳細講解一下這件事嗎？

Yeah. So, if patients are randomized, they won't receive TPA, they'll be randomized into our study. If they receive TPA prior to randomizing into our study, then we'll have to wait six hours before we know if they're a non-responder and can come into our study.

是的。因此，如果患者被隨機分配，他們將不會接受 TPA，而是被隨機分配到我們的研究中。如果他們在隨機進入我們的研究之前接受了 TPA，那麼我們必須等待六個小時才能知道他們是否對治療無反應並且可以進入我們的研究。

Got it. And then one final one, if I may in the original plan that you guys laid out 144 patients was intended to be the interim cohort for 364 patient study. And I know you just showed us an example of the simulation you did, but that was I think 350 patients at 200 is the interim analysis. So was the 360 is the 364 still a viable number or how should we think about that? Because those seem to be at odds with one another.

知道了。最後一個問題，如果可以的話，在你們最初的計劃中，144 名患者是作為 364 名患者研究的中期隊列。我知道您剛剛向我們展示了您所做的模擬的一個例子，但我認為那是對 350 名患者進行的，其中 200 是中期分析。那麼 360 和 364 仍然是一個可行的數字嗎，或者我們應該如何看待這個問題？因為它們看起來互相矛盾。

So based on 200 patients at the interim analysis and if we had the same drug effect as previous at 144 we would anticipate a lower total number of patients. So below the 364.

因此，基於中期分析的 200 名患者，如果我們的藥物效果與先前的 144 名患者相同，我們預計患者總數會較低。因此低於 364。

Okay. Got it. Appreciate you taking the question.

好的。知道了。感謝您回答這個問題。

Your next question comes from Chase Knickerbocker at Craig-Hallum.

您的下一個問題來自 Craig-Hallum 的 Chase Knickerbocker。

Good morning. Thanks for taking the questions. So just to start off a little bit to make sure I understand it. So can you help me with a bit more color around kind of the assumptions to get to a quicker final readout, you know, with these changes from a, you know, get a higher patient number at the interim, I think you might have just answered part of it, but it's just with, kind of greater, certainty around that, effect you're seeing and that allows you to resample smaller or is it kind of around the increased enrollment rate that you would expect for allowing TP a non-responders? Thanks.

早安.感謝您回答這些問題。因此，首先我要稍微確保一下我是否理解了這一點。因此，您能否幫助我更詳細地說明一下這些假設，以便更快地獲得最終讀數，您知道，隨著這些變化，從暫時獲得更高的患者數量，我想您可能只回答了部分問題，但這只是對您看到的效果的更大確定性，並且允許您重新採樣更小的樣本，還是圍繞您期望的增加的入學率，以允許 TP 無反應者？謝謝。

Yes. So basically, the way the Bayesian analysis works is that the more patients that you have in the interim analysis, the more precision that you can make around the sample size assessment. So as an example, if we have a 14% excellent outcome rate, which is what we originally had calculated when we had the 364 patients, we could potentially bring that down to 300 with an interim analysis of 200. And obviously, that would save us a lot of money and would save us a lot of time in enrollment.

是的。因此，基本上，貝葉斯分析的工作方式是，中期分析的患者越多，樣本量評估的精確度就越高。舉例來說，如果我們的優良率為 14%，這是我們在 364 名患者時最初計算出的優良率，那麼我們可以透過 200 的中期分析將優良率降至 300。顯然，這將為我們節省大量的金錢和時間。

So basically, by going to 200 it gives us the opportunity to significantly shave off time of the trial and to be much more efficient in terms of how much money we spend on the trial.

因此基本上，透過達到 200，我們可以大大縮短試驗時間，並且在試驗花費方面更有效率。

Got it. You may have answered this. I'm jumping around a couple calls, apologies. But was there anything that you kind of saw on enrollment rates or kind of overall patient care baseline characteristics that kind of drove these changes or was it mainly just around the latter point that you just made? Thanks.

知道了。您或許已經回答了這個問題。我剛剛打了幾通電話，抱歉。但是，您是否看到入學率或整體患者護理基線特徵方面的任何因素推動了這些變化，還是主要只是您剛才提到的後一點？謝謝。

Yeah, it's not that what we saw in the actual ongoing study. It was really in consultation with our statistical experts that we made these changes as we were finalizing the report for the Bayesian analysis that's going along with the SAP for submission to the FDA. So, it was really based on expert opinion.

是的，這並不是我們在實際進行的研究中看到的情況。我們在最終確定貝葉斯分析報告並隨 SAP 一起提交給 FDA 時，實際上是在與統計專家協商後才做出這些變更的。所以，這確實是基於專家意見。

And chase I can add. So, part of the of our analysis we conducted with these TPA patients that did not respond from our phase two trial, there was a very low placebo response rate, so zero, whereas we had a 25% improvement with our drug. And so, if we carry that into our current trial that should greatly help the statistical analysis plan. So, if we have a large number of patients that have a very low placebo, but a strong drug effect, it should be very beneficial for our statistical analysis plan.

我還可以添加追逐。因此，我們對這些在第二階段試驗中沒有反應的 TPA 患者進行的部分分析發現，安慰劑的反應率非常低，為零，而我們的藥物治療使病情改善了 25%。因此，如果我們將其納入當前試驗，這將極大地幫助統計分析計劃。所以，如果我們有大量的患者服用的安慰劑劑量很低，但藥物效果很強，這對我們的統計分析計劃應該非常有利。

What was the end on the TP a non responders in your previous study? How many patients was there?

在您先前的研究中，TP 無反應的結果是什麼？有多少名病人？

A total of 20. And then I'll also add part of our analysis included a pretty deep analysis of the human urinary form use in China today. So there's been about a half a dozen clinical studies showing an incremental effect of urinary KLK one on top of TPA. And that's also consistent with the discussions we've had with a number of different groups in China, with people that are treating patients there today.

共20個。然後我還要補充一點，我們的分析包括對當今中國人類尿液形態使用的相當深入的分析。大約有六項臨床研究表明，尿液 KLK 1 在 TPA 的基礎上具有增量效果。這也與我們與中國多個不同團體以及目前在那裡治療患者的人員進行的討論一致。

Got it. And just last one for me, does this have a, should we think of this as having a material impact to DM 199 commercial opportunity? Kind of what, what does it kind of expand the, you know, would you expect, I guess, would you expect a potential label to, you know, also include, you know, those that, you know, wouldn't respond to TP A and, and what could that mean kind of for the overall patient opportunity?

知道了。對我來說最後一個問題是，這是否會對 DM 199 商業機會產生重大影響？有點像，它會怎樣擴大，你知道，你會期望，我想，你會期望一個潛在的標籤，你知道，還包括那些不會對 TP A 作出反應的人，這對整體患者機會意味著什麼？

Yes, we do. And we think it will be of greater interest as well for potential partners. So as we see about a half of patients who get TPA, do not respond and So if we're looking at about 10% of patients that have a stroke get TPA so 80,000 patients and I mean, if we were able to expand our label and having another 40,000 patients a year, I mean, there's greater than a billion dollars in additional revenue in the US just for that expansion alone.

是的，我們知道。我們認為這也將引起潛在合作夥伴更大的興趣。因此，我們發現大約有一半接受 TPA 治療的患者沒有反應，因此，如果我們研究大約 10% 的中風患者接受 TPA 治療，那麼就有 80,000 名患者，我的意思是，如果我們能夠擴大我們的標籤並且每年另外有 40,000 名患者，我的額外意思是，僅帶來這一擴展就可以在美國的 10 億美元擴展。

Great. Thanks for taking the questions.

偉大的。感謝您回答這些問題。

Your next question comes from Francois Brisebois with Oppenheimer.

您的下一個問題來自 Oppenheimer 的 Francois Brisebois。

Hi, this is Dan Albert Frank. Thanks for taking my question. Just a quick one. With regards to timeline here previously, with the interim enrollment of 144 you had targeted for first quarter 25. Now with the 200 any guidance in terms of when we should be expecting the enrollment to complete?

你好，我是 Dan Albert Frank。感謝您回答我的問題。只需快速操作即可。關於先前的時間表，中期招生人數為 144 人，而您計劃第一季招生人數為 25 人。現在已經有 200 位學生了，請問我們什麼時候可以完成註冊？

Yes. So, with the intended plan to have the interim analysis in Q4, we would be looking at some time next summer.

是的。因此，我們計劃在第四季度進行中期分析，屆時我們將研究明年夏天的某個時候。

Great. Thanks for taking my question.

偉大的。感謝您回答我的問題。

Your next question comes from Matthew Caufield with H.C. Wainright.

您的下一個問題來自 H.C. 的 Matthew Caufield。溫賴特。

Thanak you for taking question. So, for preeclampsia, there was mention of the frozen versus refrigerated vials. With the dosing now commenced, will there be any patients that would have received one versus the other? And are there any complicating factors to consider there?

感謝您回答問題。因此，對於子癇前症，有提到冷凍和冷藏小瓶。現在已經開始給藥，是否會有患者選擇接受其中一種藥物而非另一種藥物？其中是否存在什麼複雜因素需要考慮？

So initially, the patients will receive the frozen product, but it's really not an issue with this particular site. Primarily they're going to be using the refrigerated product.

因此最初，患者將收到冷凍產品，但這對這個特定站點來說實際上不是一個問題。他們主要會使用冷藏產品。

Understood. And obviously, there's no anticipation of any distinction between one versus the other.

明白了。顯然，我們並不認為這兩者之間會有任何差異。

No, they're absolutely identical.

不，它們完全相同。

Okay. Got it. Thank you. And then also for ReMEDy2, there was mention of the no FDA comments received to date and obviously, proceeding. Do you feel there's any risk the agency provides subsequent feedback at this point? Necessitating trial modification once the changes are now up and running? Thanks again.

好的。知道了。謝謝。然後對於 ReMEDy2，也有提及迄今為止沒有收到 FDA 的評論，而且顯然仍在進行中。您是否認為該機構此時提供後續回饋有任何風險？一旦變更開始生效，是否需要進行試驗性修改？再次感謝。

Yeah. So traditionally the FDA response within 30 days after submission of any protocol amendment or supplemental information, we're well past the 30-day mark. So, the chances of additional FDA feedback become less and less over time. So right now, I would say our chances of receiving substantive FDA feedback is relatively low.

是的。按照慣例，FDA 會在提交任何協議修正案或補充資訊後 30 天內做出回應，但我們已經遠遠超過了 30 天的限制。因此，隨著時間的推移，獲得 FDA 額外回饋的機會變得越來越少。所以現在，我認為我們收到 FDA 實質回饋的機會相對較低。

Got you. Okay, great. I guess no answer is a good answer from in that case. So, I appreciate it. That's right from the FDA. That.

明白了。好的，太好了。我認為在這種情況下沒有答案就不是一個好的答案。所以我很感激。這是 FDA 給出的確切證據。那。

that's right.

這是正確的。

Great. Thank you guys.

偉大的。謝謝你們。

Thank you. There are no further questions at this time. I would now turn the call back to Mr Rick Puls.

謝謝。目前沒有其他問題。現在我將把電話轉回給 Rick Puls 先生。

Great. So, we'd like to thank everyone for joining us this morning and for your continued support. We look forward to a very exciting 2025 and to our next update. This concludes your call today. Thank you.

偉大的。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。我們期待著非常令人興奮的 2025 年和我們的下一次更新。今天的通話到此結束。謝謝。

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。