Brainstorm Cell Therapeutics Inc (BCLI) 2022 Q1 法說會逐字稿

Greetings, and welcome to the Brainstorm Cell Therapeutics first-quarter 2022 conference call. At this time, all participants are in a listen only mode. As a reminder, this call is being recorded.

您好，歡迎來到 Brainstorm Cell Therapeutics 2022 年第一季度電話會議。此時，所有參與者都處於只聽模式。提醒一下，此通話正在錄音中。

And I would now like to introduce your host for today's conference, Tom Galassi of LifeSci Advisors. Mr. Galassi, you may begin.

現在我想介紹一下今天會議的主持人，來自 LifeSci Advisors 的 Tom Galassi。 Galassi 先生，您可以開始了。

Good morning, and thank you for joining us. Before we begin the opening remarks, we would like to remind listeners that this conference call contains numerous statements, descriptions, forecasts and projections regarding Brainstorm Cell Therapeutics and its potential future operations and performance. Statements regarding the market potential for the treatment of neurodegenerative disorders such as ALS and MS, the sufficiency of the company's existing capital resources for continuing operations in 2022 and beyond, the safety and clinical effectiveness for the NurOwn technology platform, clinical trials of NurOwn and related clinical development programs, and the company's ability to develop strategic collaborations and partnerships to support their business planning efforts.

早上好，感謝您加入我們。在開始致開幕詞之前，我們想提醒聽眾，本次電話會議包含大量關於 Brainstorm Cell Therapeutics 及其未來潛在運營和業績的聲明、描述、預測和預測。關於治療 ALS 和 MS 等神經退行性疾病的市場潛力、公司現有資本資源是否足以在 2022 年及以後持續運營、NurOwn 技術平台的安全性和臨床有效性、NurOwn 及相關臨床試驗的聲明臨床開發計劃，以及公司發展戰略合作和夥伴關係以支持其業務規劃工作的能力。

Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond Brainstorm's control, including the risks and uncertainties described from time to time in its SEC filings. The company's results may differ materially from those projected on today's call. The company undertakes no obligation to publicly update any forward-looking statements.

前瞻性陳述受到眾多風險和不確定因素的影響，其中許多風險和不確定因素超出了 Brainstorm 的控制範圍，包括在其提交給美國證券交易委員會的文件中不時描述的風險和不確定因素。該公司的結果可能與今天電話會議上預測的結果存在重大差異。公司不承擔公開更新任何前瞻性陳述的義務。

Joining me on the call today will be Chaim Lebovits, CEO, Brainstorm and Alla Patlis, Interim Chief Financial Officer. In addition, Dr. Stacy Lindborg, Executive Vice President and Chief Development Officer, Dr. Ralph Kern, President and Chief Medical Officer, and Dr. David Setboun, Executive Vice President and Chief Operating Officer, are also on the call and will be available to answer your questions during the Q&A session.

今天與我一起參加電話會議的有 Brainstorm 首席執行官 Chaim Lebovits 和臨時首席財務官 Alla Patlis。此外，執行副總裁兼首席開發官 Stacy Lindborg 博士、總裁兼首席醫療官 Ralph Kern 博士和執行副總裁兼首席運營官 David Setboun 博士也將出席電話會議，屆時將有空在問答環節回答您的問題。

Now I'd like to turn the call over to Mr. Lebovits. Please go ahead.

現在我想把電話轉給 Lebovits 先生。請繼續。

Thanks, Tom. Thank you to all listening for joining us to discuss our first quarter financial results and corporate highlights. Given that we provided a detailed update on our clinical programs during our year-end call only about six weeks ago, I'll keep my prepared remarks brief today, as is our usual practice, will follow our prepared remarks addressing questions we received from investors in advance as well as taking live questions from those of you listening on the call today.

謝謝，湯姆。感謝所有聆聽者加入我們討論我們的第一季度財務業績和公司亮點。鑑於我們僅在大約六週前的年終電話會議上提供了有關臨床計劃的詳細更新，今天我將按照我們的慣例，按照我們準備好的評論回答投資者提出的問題，簡要介紹我準備好的評論提前以及從你們今天聽電話的人那裡接受現場提問。

I want to emphasize that Brainstorm's highest priority is pursuing the optimal path forward to provide broad access to NurOwn for patients with ALS. Our continued efforts towards this goal are moving forward, and have been advanced in many ways, including ongoing interactions with ALS experts, world-renowned [satetitans] and leaders from the clinical and patient communities.

我想強調的是，Brainstorm 的最高優先級是尋求最佳的前進道路，為 ALS 患者提供廣泛的 NurOwn 服務。我們為實現這一目標所做的持續努力正在向前推進，並在許多方面取得了進展，包括與 ALS 專家、世界知名 [satetitans] 以及來自臨床和患者社區的領導者的持續互動。

As I previously stated, valuable feedback and insights gained from these interactions are critical and are guiding the specific steps we will take to move NurOwn forward. Our dedicated team has continuously received excellent feedback on the NurOwn clinical data set since our phase 3 trial's initial top line readout. However, insights provided to us throughout the first quarter have been particularly insightful, given that we have published our full results near the end of 2021. The visibility of the phase 3 publication enabled us to provide the ALS expert community with a full and transparent view of our randomized placebo-controlled phase 3 trial data that has been validated through the rigorous peer review process. As a reminder, although the phase 3 trial did not see statistical significant primary or secondary endpoints, prespecified and post-hoc analyses showed NurOwn delivering robust clinical benefits to ALS patients with less advanced disease. These clinical findings are further supported by biomarker data, showing significant NurOwn driven changes across important ALS disease pathways such as those related to neuro protection and neuro inflammation.

正如我之前所說，從這些互動中獲得的寶貴反饋和見解至關重要，並且正在指導我們為推動 NurOwn 向前發展而採取的具體步驟。自我們的第 3 階段試驗的初始頂線讀數以來，我們敬業的團隊不斷收到關於 NurOwn 臨床數據集的出色反饋。然而，鑑於我們已在 2021 年底發布了全部結果，整個第一季度提供給我們的見解特別有見地。第 3 階段出版物的可見性使我們能夠為 ALS 專家社區提供完整和透明的視圖我們的隨機安慰劑對照 3 期試驗數據已通過嚴格的同行評審過程得到驗證。提醒一下，雖然 3 期試驗沒有發現具有統計學意義的主要或次要終點，但預先指定的和事後分析表明 NurOwn 為疾病較輕的 ALS 患者帶來了強大的臨床益處。這些臨床發現得到了生物標誌物數據的進一步支持，表明 NurOwn 驅動的顯著變化跨越重要的肌萎縮側索硬化疾病通路，例如與神經保護和神經炎症相關的通路。

Since the publication of our paper, we have had the opportunity to present data from our phase 3 trial at three scientific conferences, including the MD&A annual meeting and the American Academy of Neurology. And we will deliver an additional biomarker presentation coming up at the first ALS Drug Development Summit later this month. We have been highly encouraged by the feedback received to date, which we are incorporating into our business and regulatory strategy as we move forward. Given the sensitive and confidential nature of our ongoing communications with the regulatory authorities, we are not in a position today to disclose the specifics of these interaction.

自我們的論文發表以來，我們有機會在三個科學會議上展示我們的 3 期試驗數據，包括 MD&A 年會和美國神經病學學會。我們將在本月晚些時候的第一屆 ALS 藥物開發峰會上發表額外的生物標誌物介紹。迄今為止收到的反饋讓我們深受鼓舞，在我們前進的過程中，我們正在將這些反饋納入我們的業務和監管戰略。鑑於我們與監管機構持續溝通的敏感性和機密性，我們今天無法透露這些互動的細節。

I'll stress however, that we continue to make tangible progress behind the scenes, and I look forward to when we can share a comprehensive update. We appreciate the urgency of the needs facing the ALS community, and I ensure you all, that our entire team is working diligently through a coordinated effort to address these needs as expeditiously as possible.

不過，我要強調的是，我們在幕後繼續取得切實進展，我期待著我們何時可以分享全面的更新。我們理解 ALS 社區面臨的緊迫需求，我向大家保證，我們的整個團隊正在通過協調一致的努力努力工作，以盡快滿足這些需求。

In parallel with our efforts to advance NurOwn down its optimal path forward, we also continue to [pray for] exhibited growth by adding talented and dedicated individuals to our leadership team. Just this past week, we announced the appointment of Dr. Netta Blondheim-Shraga as VP of Research and Development and Antal Pearl-Lendner to the newly-created position of Chief Legal Counsel. We are thrilled to welcome both Antal and Netta to Brainstorm and expect the complementary skillsets and experience working within this industry leaders such as GE Capital and Teva Pharmaceuticals, respectively, to be supportive and help to drive our continuous progress.

在我們努力推動 NurOwn 走上最佳前進道路的同時，我們還通過在我們的領導團隊中增加有才華和敬業的個人來繼續 [祈禱] 展示增長。就在上週，我們宣布任命 Netta Blondheim-Shraga 博士為研發副總裁，並任命 Antal Pearl-Lendner 為新設立的首席法律顧問一職。我們很高興歡迎 Antal 和 Netta 加入 Brainstorm，並期待在 GE Capital 和 Teva Pharmaceuticals 等行業領導者中工作的互補技能和經驗能夠支持並幫助推動我們不斷進步。

Turning to our pipeline, we continue to make progress developing our proprietary exosome-based platform and technology, which has applications in multiple disease areas. Dr. Kim Thacker, our Senior Vice President of Medical Affairs and Clinical Innovation, presented new preclinical data from this program at the International Society of Cell and Gene Therapy Conference earlier this month in San Francisco. This data look upon prior pre-clinical produce that demonstrated the superior efficacy of NurOwn derived exosomes in a model of acute lung injury when compared with exosome that had been produced from naive mesenchymal stem cells.

談到我們的管道，我們繼續在開發我們專有的基於外泌體的平台和技術方面取得進展，該平台和技術在多個疾病領域都有應用。我們負責醫療事務和臨床創新的高級副總裁 Kim Thacker 博士本月早些時候在舊金山舉行的國際細胞和基因治療學會會議上介紹了該項目的新臨床前數據。該數據著眼於之前的臨床前產品，證明了與從幼稚間充質乾細胞產生的外泌體相比，NurOwn 衍生的外泌體在急性肺損傷模型中具有更好的療效。

With new data presented at ISCT, we gained important insights into the biologic mechanisms underlying the superior efficacy of NurOwn-derived exosomes, which appears to be linked to their anti-inflammatory effects on macrophage populations. We look forward to discussing our exosome program further during an upcoming presentation at the ISEV 2022 Annual Meeting, which is taking place in Lyon, France on May 26. I will now turn the call over to Alla Patlis, who will review our financials. Alla?

通過在 ISCT 上展示的新數據，我們獲得了對 NurOwn 衍生外泌體卓越功效背後的生物學機制的重要見解，這似乎與它們對巨噬細胞群的抗炎作用有關。我們期待在即將於 5 月 26 日在法國里昂舉行的 ISEV 2022 年會上的演講中進一步討論我們的外泌體計劃。我現在將電話轉給 Alla Patlis，他將審查我們的財務狀況。阿拉？

Thank you, Chaim. It is my pleasure now to discuss our financial results for the first quarter ended March 31, 2022. Brainstorm's cash, cash equivalents and short-term bank deposits were approximately $18.4 million as of March 31, 2022. This compares with approximately $22.1 million on December 31, 2021. Our research and development expenditures net in the first quarter of 2022 were $2.6 million compared with $4.3 million for the comparable periods in 2021. General and administrative expenses for the first quarter were $2.8 million compared with $2.6 million in the comparable period of 2021. Net loss for the first quarter was $5.4 million or $0.15 per share as compared to net loss of $6.7 million or $0.19 per share for the comparable period in 2021. Back to you, Chaim.

謝謝你，柴姆。我現在很高興討論我們截至 2022 年 3 月 31 日的第一季度的財務業績。截至 2022 年 3 月 31 日，Brainstorm 的現金、現金等價物和短期銀行存款約為 1840 萬美元。相比之下，去年 12 月約為 2210 萬美元2021 年 3 月 31 日。我們在 2022 年第一季度的研發支出淨額為 260 萬美元，而 2021 年同期為 430 萬美元。第一季度的一般和行政費用為 280 萬美元，而同期為 260 萬美元2021 年第一季度淨虧損為 540 萬美元或每股 0.15 美元，而 2021 年同期淨虧損為 670 萬美元或每股 0.19 美元。回到你身邊，Chaim。

Thank you Alla. Wonderful job, Tom Galassi from LifeSci will now read the questions we have received from investors. Tom?

謝謝阿拉。幹得好，來自 LifeSci 的 Tom Galassi 現在將閱讀我們從投資者那裡收到的問題。湯姆？

Thanks, Chaim. Our first question is, if you could provide an update on the regulatory status of NurOwn in ALS?

謝謝，柴姆。我們的第一個問題是，您是否可以提供有關 NurOwn 在 ALS 中的監管狀態的最新信息？

Stacy, you want to take it?

史黛西，你要拿走嗎？

As Chaim mentioned in his prepared comments, we continue to leverage expert feedback as we work collaboratively with regulators to enable NurOwn's advancements. Our aim is to seek the most expeditious path forward to enable patient access. And at this time, at the same time, create value for our stakeholders.

正如 Chaim 在他準備好的評論中提到的那樣，我們在與監管機構合作以推動 NurOwn 進步的過程中繼續利用專家反饋。我們的目標是尋求最快捷的途徑，使患者能夠進入。同時，為我們的利益相關者創造價值。

Okay. For our second question we have, what are you gaining from recent presentations at scientific conferences?

好的。對於我們的第二個問題，您從最近在科學會議上的演講中獲得了什麼？

Yes, I'll ask Ralph to do that. I'm just sharing with the shareholders and the other people listening, again, that I think is the first time in a long time since corona, that we're doing the call in the same room in our offices in Boston and Burlington. And Ralph's here, take it.

是的，我會請拉爾夫這樣做。我只是與股東和其他聽眾分享，我認為這是自冠狀病毒以來很長一段時間以來的第一次，我們在波士頓和伯靈頓辦公室的同一個房間裡打電話。拉爾夫在這裡，拿著它。

Thanks, Chaim. As we mentioned, we continue to broaden our understanding of NurOwn's mechanism of action in ALS and in progressive MS, while at the same time, providing key scientific insights into the enhanced immunomodulation or protection of our platform technology. These really important scientific insights that we will share over the next few months will support a few activities, first of all regulatory activities. Secondly, though definitely increased scientific credibility with the broad scientific community. And finally, will provide support for both internal and external discussions related to strategic partnerships.

謝謝，柴姆。正如我們所提到的，我們繼續拓寬我們對 NurOwn 在 ALS 和進行性 MS 中的作用機制的理解，同時，為增強免疫調節或保護我們的平台技術提供關鍵的科學見解。我們將在接下來的幾個月中分享這些非常重要的科學見解，將支持一些活動，首先是監管活動。其次，儘管確實提高了廣大科學界的科學可信度。最後，將為與戰略夥伴關係相關的內部和外部討論提供支持。

Thank you.

謝謝。

Our next question asks, can you provide an update on your progressive MS program?

我們的下一個問題是，您能否提供有關您的漸進式 MS 計劃的最新信息？

Yes, That's also Ralph.

是的，那也是拉爾夫。

Thank you. As we mentioned, we've completed additional analyses of the phase 2 study, and we plan to share these insights at the upcoming CMSC meeting in June in DC and at the [Exterims] meeting in the fall, which will be in the Netherlands. These scientific presentations will support continued development of NurOwn in progressive MS in our view, but we've also received valuable feedback from MS scientific experts and regulators over the last 2 months and once the phase 2 study is published in the peer-reviewed journal we'll provide a further update.

謝謝。正如我們提到的，我們已經完成了對 2 期研究的額外分析，我們計劃在即將於 6 月在華盛頓舉行的 CMSC 會議和秋季在荷蘭舉行的 [Exterims] 會議上分享這些見解。我們認為，這些科學報告將支持 NurOwn 在進展型 MS 中的持續發展，但在過去 2 個月中，我們也收到了來自 MS 科學專家和監管機構的寶貴反饋，一旦 2 期研究在同行評審期刊上發表，我們將提供進一步的更新。

Thank you, Ralph.

謝謝你，拉爾夫。

Okay. And the last pre-submitted question asks, can you provide an update on your ALS expanded access program?

好的。最後一個預先提交的問題是，您能否提供有關 ALS 擴展訪問計劃的最新信息？

Sure, thank you, Tom. We continue to provide additionally a few treatments through the intermediate sized EAP protocol that the FDA has approved. We continue to actively collect clinical and biomarker data from this program and hope to provide further updates as they become available. It was the best success to all the patients getting treatments these weeks.

當然，謝謝你，湯姆。我們繼續通過 FDA 批准的中等規模的 EAP 協議提供額外的一些治療。我們繼續從該計劃中積極收集臨床和生物標誌物數據，並希望在可用時提供進一步的更新。對於這幾週接受治療的所有患者來說，這是最好的成功。

[Jenny], I would like you to please open the call for questions from people on the call.

[珍妮]，我希望你能打開通話中的人提問的電話。

No problem at all. (Operator Instructions)

完全沒有問題。 （操作員說明）

David Bautz, Zacks Small-Cap Research.

David Bautz，Zacks 小型股研究公司。

Hey, good morning, everybody. While I know you can't go into the details, I'm just curious if you've had any further meetings with the FDA or if you guys do decide to go down the path of filing a BLA, would you plan on having additional meetings with the FDA before you do that?

嘿，大家早上好。雖然我知道你們不能深入細節，但我只是想知道你們是否與 FDA 有過任何進一步的會議，或者你們是否決定沿著提交 BLA 的道路前進，你們是否計劃有額外的在你這樣做之前與 FDA 會面？

I'll answer on the second part of the question and -- There are different ways how you can talk to regulators. There are official meetings, and if there is sometimes say, important programs to the agency, they have ways to talk to us. So we keep on saying that we have an ongoing conversation with regulatory and that's true. It continues to be true. That's as far as I can go this morning, David. I know we discussed it also offline and also with other investors, everyone wants to know where we are. We'll share as soon as we can. We are doing the best for shareholders of not yet sharing where we are. But everything is on course. And to your question, yes.

我將回答問題的第二部分——您可以通過不同的方式與監管機構交談。有正式會議，如果有時對機構來說是重要的計劃，他們有辦法與我們交談。所以我們一直說我們正在與監管機構進行對話，這是真的。它仍然是正確的。大衛，今天早上我只能說這麼多了。我知道我們也在線下和其他投資者討論過它，每個人都想知道我們在哪裡。我們會盡快分享。我們正在為尚未分享我們所處位置的股東盡最大努力。但一切都在進行中。對於你的問題，是的。

Okay, thanks. Now regarding exosomes. I'm curious what the potential other indications you could look at for that platform outside of the acute lung injury, which you've already shown preclinical data for us today.

好的謝謝。現在關於外泌體。我很好奇您可以在急性肺損傷之外為該平台尋找哪些潛在的其他適應症，您今天已經為我們展示了臨床前數據。

It is a wonderful question. Again, I can't share too much, but I will share with you that we just shared that we just appointed a new VP R&D and she has a lot of expertise in that exactly to drive from the scientific good indication to drive to -- Okay, where's this going? What are the diseases? Who are the right partners? That's what she has done in Teva with their huge consortiums and bringing things from academic through to company development.

這是一個很好的問題。再次重申，我不能分享太多，但我會與您分享我們剛剛分享的內容，我們剛剛任命了一位新的研發副總裁，她在這方面擁有豐富的專業知識，可以從科學的良好跡象推動到——好的，這是要去哪裡？有哪些疾病？誰是合適的合作夥伴？這就是她在 Teva 與他們龐大的財團所做的事情，並將學術上的東西帶到公司發展中。

So of course, we are not academic, but our R&D team, is more academic driven and it's going to be much more business focused and also to try to figure out with who the partner and what different indications. It's a very good question. So we're looking at the whole broad possibilities and she is very professional with the team, and she may bring more people to assist her to exactly be able to outline the company to move very fast in the right direction. So while we are already focused on lung disease in different ways and that will be an add-on this year. Exosomes are becoming very, very hot in our industry, as you know.

因此，當然，我們不是學術性的，但我們的研發團隊更受學術驅動，它將更加關注業務，並試圖找出與合作夥伴的合作夥伴以及不同的適應症。這是一個很好的問題。因此，我們正在研究整個廣泛的可能性，她對團隊非常專業，她可能會帶來更多的人來幫助她，以準確地概述公司，使其朝著正確的方向快速發展。因此，雖然我們已經以不同的方式關注肺部疾病，但今年這將是一個附加項目。如您所知，外泌體在我們的行業中變得非常非常熱門。

Yep. All right, sounds good. Thanks for taking the questions this morning.

是的。好吧，聽起來不錯。感謝您今天早上提出問題。

Thank you. Michelle Lorenz, Voices for ALS.

謝謝。 Michelle Lorenz，ALS 之聲。

Good morning, everybody. I've four questions. Two about biomarkers and two about patient reported outcomes. The first biomarker question relates to your CSF biomarkers. At the AdComm and SEDARS, Dr. Billy Dunn talked about the importance of neurofilament light trending in the right direction, and earlier last year or at the end of last year, Dr. Brown said that the NFL in the neuron trial was trending, I think his quote was eye-popping. So I'm curious if you can comment on which of the CSF biomarkers you found the most compelling, and did you see a larger magnitude difference in the higher ALS FRS scores just as you did in the clinical trial data with the -- that was published in Muscle & Nerve?

大家早上好。我有四個問題。兩個關於生物標誌物，兩個關於患者報告的結果。第一個生物標誌物問題與您的 CSF 生物標誌物有關。在 AdComm 和 SEDARS 上，Billy Dunn 博士談到了神經絲光趨勢在正確方向上的重要性，而去年早些時候或去年年底，Brown 博士說 NFL 在神經元試驗中的趨勢，我認為他的話令人大跌眼鏡。所以我很好奇你是否可以評論你發現哪些 CSF 生物標誌物最引人注目，你是否看到較高的 ALS FRS 分數存在更大的差異，就像你在臨床試驗數據中所做的那樣 - 那是發表於肌肉與神經？

Thank you so much. The answer for that is, that we are not claiming a single biomarker support only. We don't think ALS and none of our scientists or neurologists think that ALS will be driven only by a single biomarker. We do know. And as you mentioned, Dr. Billy Dunn and AdComm for analysts has mentioned that he would like to see NFL going in the right direction as an additional credibility to ALS FRS results. We can say that we have that. And not only with NFL, we have many biomarkers supporting our ALS FRS, the core story that we are claiming that shows that our trial is -- that our treatment is efficient. We did lay out part of the biomarker story in our manuscript, but there's still so much to share and we are working in an additional manuscript that will lay out actually a lot of what you were asking in more detail.

太感謝了。答案是，我們並不是只要求單一的生物標誌物支持。我們不認為 ALS，我們的科學家或神經學家都不認為 ALS 將僅由單一生物標誌物驅動。我們知道。正如你提到的，Billy Dunn 博士和 AdComm 分析師已經提到，他希望看到 NFL 朝著正確的方向前進，作為 ALS FRS 結果的額外可信度。我們可以說我們有。不僅是 NFL，我們有許多生物標誌物支持我們的 ALS FRS，我們聲稱的核心故事表明我們的試驗是——我們的治療是有效的。我們確實在我們的手稿中列出了部分生物標誌物的故事，但還有很多東西要分享，我們正在編寫一份額外的手稿，它實際上會更詳細地列出你所問的很多內容。

You may not be able to answer the second one, then. I noticed that Dr. [Sakovich] presented at the M&E talking about UNC13A and about I think the data was about 65% of the people with the [ACLEO] met the primary endpoint. That was roughly about five times P value. So given that UNC13A's a mispricing error. Do you hypothesize that NurOwn may show efficacy on the other genes that have misplacing error, that were identified in Aaron Getler's paper in nature?

那麼你可能無法回答第二個問題。我注意到 [Sakovich] 博士在 M&E 上談到了 UNC13A，我認為數據是大約 65% 的 [ACLEO] 患者達到了主要終點。那大約是 P 值的五倍。因此，鑑於 UNC13A 是一個錯誤定價錯誤。您是否假設 NurOwn 可能對 Aaron Getler 的自然界論文中確定的其他具有錯位錯誤的基因有效？

You're asking a very good question and Dr. Sakovich could did share whatever would be able to be shared at the time. It doesn't mean that we have that we say that only A versus C works. It is it is far more complex. As you know, I think first of all, for the code, if you really follow our presentations, very good and a lot of detail, happy to see that. And our scientists are very excited that we are paving the way. First in biomarkers, someone following many ALS trials, I know that, you know, it was the first with the largest biomarker data set to bring forward in an ALS trial. And now thank God, all of the trials are now understanding that biomarkers has to be part of trial collection. And even though it's another CSF tap again, and again, which we rather not do the patients, but patients are very happy.

你問了一個很好的問題，Sakovich 博士確實可以分享當時可以分享的任何內容。這並不意味著我們說只有 A 對 C 有效。它要復雜得多。如您所知，我認為首先，對於代碼，如果您真的按照我們的介紹進行操作，那麼非常好並且有很多細節，很高興看到。我們的科學家對我們正在鋪平道路感到非常興奮。首先在生物標誌物方面，有人跟踪了許多 ALS 試驗，我知道，這是第一個在 ALS 試驗中提出最大生物標誌物數據集的人。現在感謝上帝，所有的試驗現在都明白生物標誌物必須成為試驗收集的一部分。儘管這是一次又一次的腦脊液穿刺，我們寧願不給病人做，但病人還是很高興。

They know that whatever is happening in the trial, they are really, really giving a lot of support for science going forward, understanding ALS better. But I think our data set of biomarkers brings that into genetics. We just -- it's just on the surface. So we're opening the door there. We're showing very interesting data, as you mentioned and we can of course, include that now in our biomass paper. It will have the genetics section, but it's only the beginning. I think our biomarker data will be far more helpful at this moment than the genetic data. But the genetic data is very supportive of what we are saying definitely.

他們知道，無論試驗中發生什麼，他們確實非常非常支持科學的發展，更好地了解肌萎縮側索硬化。但我認為我們的生物標誌物數據集將其帶入了遺傳學。我們只是 - 它只是在表面上。所以我們在那裡打開大門。正如您提到的，我們正在展示非常有趣的數據，我們當然可以將其包含在我們的生物質論文中。它會有遺傳學部分，但這只是開始。我認為我們的生物標誌物數據此時將比遺傳數據更有幫助。但是遺傳數據非常支持我們所說的。

To that end, I'm also a believer that the patient reported outcomes are compelling. And as you know, sadly, that the COVID halted the collection of breathing data in the phase 3 trial. But it appears from the people in EAP, both the last EAP that some people were having significant improvements in FCC. Some one person obviously stopped using a trilogy and it's been two years, I checked with his family, they still aren't using the trilogy two years since his last dose. So I'm curious, is NurOwn up-regulating the epidermal growth factor? Or is there another biomarker that you believe might be responsible for targeting that phrenic nerve that innervates the diaphragm?

為此，我也相信患者報告的結果是令人信服的。如您所知，可悲的是，COVID 停止了 3 期試驗中呼吸數據的收集。但從 EAP 的人們看來，這兩個 EAP 都是最後一個 EAP，有些人在 FCC 方面有了重大改進。有人顯然停止使用三部曲，已經兩年了，我和他的家人核實過，自從他最後一次服藥兩年後，他們仍然沒有使用三部曲。所以我很好奇，NurOwn 是否會上調表皮生長因子？或者您認為是否有另一種生物標誌物可能負責靶向支配橫膈膜的膈神經？

Michelle, I wish all the investors would know what you know in detail. But you know it, I can't comment on this AAP opening program. Wow, you follow everything. Nice.

米歇爾，我希望所有的投資者都能詳細了解你所知道的。但是你知道的，我不能對這個 AAP 開放程序發表評論。哇，你什麼都跟著。好的。

Okay --

好的 -

I can't really comment on the --

我真的不能評論——

Then the only -- the last question --

那麼唯一的——最後一個問題——

-- I can say, You know what, I'll say that. We are very happy that we're able to provide, of course, the AP that, of course, have given everyone all that. We have done -- naturally will other companies will do. We're a small market [advisor] company, investing a lot of our money and resources to provide to these few patients at least more and more treatments. We're very happy that the FDA is supporting this program in a very strong way. And then yes, we will see what you've seen shall we see the same things. Of course, we're not seeing wrong things, but we just can't comment them.

-- 我可以說，你知道嗎，我會這麼說。當然，我們很高興能夠提供 AP，當然，它已經為每個人提供了所有這些。我們已經做到了——其他公司自然也會這樣做。我們是一家小型市場[顧問]公司，投入大量資金和資源為這些少數患者提供至少越來越多的治療。我們很高興 FDA 以非常有力的方式支持該計劃。然後是的，我們會看到你所看到的，我們會看到同樣的東西嗎？當然，我們沒有看到錯誤的東西，但我們不能評論它們。

Okay. Then the last quick question is again, in EAP, a lot of people have reported that their fasciculations have stopped immediately after getting their NurOwn injection. That's obviously nowhere reflected in the ALS FRSR. How is Brainstorm capturing this data to provide evidence to the FDA and supportive how a patient feels and functions?

好的。最後一個快速問題又是，在 EAP 中，很多人報告說他們的肌束震顫在註射 NurOwn 後立即停止。這顯然沒有反映在 ALS FRSR 中。 Brainstorm 如何收集這些數據以向 FDA 提供證據並支持患者的感覺和功能？

Again, Michelle, it's a very, very good question. You know, the whole industry is discussing about the endpoints and about the score. Of course, this quarter is something that we have to hold up and the results that the scores show are also, I think, very impressive with our trial.

米歇爾，這是一個非常非常好的問題。你知道，整個行業都在討論終點和分數。當然，這個季度是我們必須堅持的事情，我認為分數顯示的結果也非常令人印象深刻。

Outside of that, you're asking a good question and there's a lot of answers, but not no final answer that we can really share here. I think the industry is going to come up with answers because you're bringing up three important points, so the score does not, of course, cover every improvement. We know that. It's well written in literature. I'm sure you know that as well. And we are talking to many people, including editors and authors of the LSFRSR score. And they want to know our data and looking at those things. And then maybe and they will share some of their thoughts very soon where maybe, but it's not for us to really add it to the score. It's for us to bring forward our data and share it as we can with the whole community to help everyone understand better how to measure ALS.

除此之外，你問的是一個很好的問題並且有很多答案，但並不是沒有我們可以在這裡真正分享的最終答案。我認為業界會給出答案，因為你提出了三個重要點，所以分數當然不會涵蓋所有改進。我們知道。它在文學中寫得很好。我相信你也知道這一點。我們正在與很多人交談，包括 LSFRSR 分數的編輯和作者。他們想知道我們的數據並查看這些東西。然後也許，他們很快就會分享他們的一些想法，也許，但我們不能真正將其添加到樂譜中。我們應該提出我們的數據並儘可能與整個社區分享，以幫助每個人更好地了解如何衡量 ALS。

But these are all very good questions. Even though you're taking up our time quite a lot, I'm very happy to answer these very professional questions. Thank you.

但這些都是非常好的問題。雖然你佔用了我們很多時間，但我很樂意回答這些非常專業的問題。謝謝。

Thank you for your time.

感謝您的時間。

Sure. [Jennie]?

當然。 [珍妮]？

Thank you. Daniel Walker, Ness Industries.

謝謝。 Ness Industries 的 Daniel Walker。

Yes, good morning. No one has a very broad mechanism of action in terms of its impact on multiple critical biomarkers. It seems like a lot of other therapies' mechanism of action are much more narrow or end up targeting a subgroup. Maybe can Dr. Kern just comment on the advantages of NurOwn's mechanism of action relative to other therapies in development, both path and present? And I do have a few other questions.

是的，早上好。就其對多種關鍵生物標誌物的影響而言，沒有人擁有非常廣泛的作用機制。似乎許多其他療法的作用機制要狹窄得多或最終只針對一個亞組。也許 Kern 博士可以評論一下 NurOwn 的作用機制相對於其他正在開發的療法的優勢，無論是路徑還是現在？我還有其他幾個問題。

Yes, hi, Daniel. We'll let Dr. Kern answer your questions. I spoke too much this morning. Dr. Kern?

是的，嗨，丹尼爾。我們會讓克恩博士回答您的問題。今天早上我說得太多了。克恩博士？

Yes, Daniel, thanks for that question. I think there's a couple of answers that would help shed some light on the point that you're raising. The first is that there's not a single neuroprotective factor that has been shown to be effective. And in fact, there's good reason for that because there are different targets that the neural protective factors reach and in the preclinical models, there's pretty good evidence that targeting a single neuroprotective factor isn't as good as targeting multiple. So they have something called synergy, so they work together. So that's kind of the first cut that I would offer.

是的，丹尼爾，謝謝你提出這個問題。我認為有幾個答案可以幫助闡明您提出的觀點。首先是沒有一種神經保護因子被證明是有效的。事實上，這是有充分理由的，因為神經保護因子達到的目標不同，而且在臨床前模型中，有很好的證據表明針對單一神經保護因子不如針對多種神經保護因子。所以他們有一種叫做協同作用的東西，所以他們一起工作。所以這是我要提供的第一個剪輯。

The second is that offering neuroprotection without managing the inflammation in the disease is probably not going to be effective and there also is some evidence to suggest that combining treatments that address both neuro protection, in other words, allowing the tissue to recover from the disease, while at the same time, reducing inflammation are more likely to be effective. So we think that there's good scientific rationale for this.

第二個是在不控制疾病炎症的情況下提供神經保護可能不會有效，而且還有一些證據表明，結合解決神經保護的治療，換句話說，讓組織從疾病中恢復，同時，減少炎症更有可能是有效的。所以我們認為這有很好的科學依據。

And then finally, the treatment technology platform that we're providing is a way of packaging both of those treatments into a single, delivery mechanism. So we think that we have a unique way of providing effective treatments across multiple pathways. And I think as Chaim mentioned earlier, our biomarker data supports that scientific perspective. In fact --

最後，我們提供的治療技術平台是一種將這兩種治療方法打包成單一遞送機制的方法。所以我們認為我們有一種獨特的方式來提供跨多種途徑的有效治療。我認為正如 Chaim 之前提到的那樣，我們的生物標誌物數據支持這種科學觀點。實際上 -

Thank you so much. And no one is showing a highly significant burden of proof in terms of ALS FRS biomarkers, UNC13A and most importantly, patient reported outcome, maybe conductor limbo or just provide some comments about how this compares to other ALS therapy in development both past and present?

太感謝了。沒有人在 ALS FRS 生物標誌物、UNC13A 以及最重要的是患者報告的結果方面表現出非常重要的舉證責任，也許是導體的邊緣，或者只是提供一些關於這與過去和現在發展中的其他 ALS 療法相比如何的評論？

Thank you for the question, Daniel. I don't think it's appropriate to comment relative to other therapies but I will echo the comments that you're providing what is very exciting about our data, which we have in the public domain, as we understand the participants that were enrolled in the trial, and we are accounting for floor effects in from the study, we see a very clinically meaningful events that are measured through the traditional scale of ALS FRSR we then also, as Dr. Kern just walked through, have seen some incredibly exciting results, large magnitudes and across a diverse set of biomarkers and our biomarker data. And really, as would have been, I guess, hope for based on literature. We're also seeing participants that have that carry the risk allele UNC13A, having had a differentiated response to treatment almost an odds ratio of nine times the response with the AC genotype.

謝謝你的問題，丹尼爾。我認為相對於其他療法發表評論是不合適的，但我會回應你提供的關於我們數據的非常令人興奮的評論，我們在公共領域擁有這些數據，因為我們了解參加該研究的參與者試驗，我們正在考慮研究中的底部效應，我們看到了一個非常具有臨床意義的事件，這些事件是通過 ALS FRSR 的傳統量表測量的，然後我們也像克恩博士剛剛走過的那樣，看到了一些令人難以置信的令人興奮的結果，大規模和跨一組不同的生物標誌物和我們的生物標誌物數據。真的，我想，希望基於文學。我們還看到攜帶風險等位基因 UNC13A 的參與者對治療有差異化反應，其優勢比幾乎是 AC 基因型反應的 9 倍。

So we really see across a collection of measures, which I think is one of the most important factors of really understanding what we believe about a product. And I think it paints some -- it paints a very important picture for what we believe about NurOwn, and the last comment I would make is really intermingling these endpoints. So we have the ability and we published this in our Muscle & Nerve paper to understand, do the biomarkers help explain the clinical response that we see with the ALSFRS-R. And in fact, as we published on, they do with very high predictive nature.

所以我們真的看到了一系列的措施，我認為這是真正理解我們對產品的看法的最重要因素之一。我認為它描繪了一些——它描繪了一幅非常重要的畫面，說明我們對 NurOwn 的看法，而我要發表的最後評論實際上是將這些端點混合在一起。因此，我們有能力並在我們的肌肉與神經論文中發表了這一點，以了解生物標誌物是否有助於解釋我們在 ALSFRS-R 中看到的臨床反應。事實上，正如我們發表的那樣，它們具有非常高的預測性。

So I think that counter to maybe comparing to other therapies, really, what we're very excited about is the consistency of measures and really how everything ultimately, if we saw clinical response, we couldn't explain through biomarkers or vice versa, we would certainly be scratching our heads a little bit more. But what we actually see is, in fact, a very strong tie that really gives a very strong explanation for the effects observed.

所以我認為這與可能與其他療法相比相反，真的，我們非常興奮的是措施的一致性，以及最終，如果我們看到臨床反應，我們無法通過生物標誌物來解釋一切，反之亦然，我們肯定會讓我們更加抓耳撓腮。但事實上，我們實際看到的是一條非常牢固的聯繫，它確實為觀察到的效果提供了非常有力的解釋。

Thank you, Stacey.

謝謝你，斯泰西。

Thank you so much and can Dr. Setboun, based on his past experiences maybe just provide some insights into how he has seen companies in similar late-stage development, think about outside partnerships and collaborations? And then maybe Chaim, for you, how is Brainstorm thinking about this particular issue and topic?

非常感謝，Setboun 博士能否根據他過去的經驗提供一些見解，了解他如何看待處於類似後期發展階段的公司，考慮外部夥伴關係和合作？然後也許 Chaim，對你來說，Brainstorm 如何思考這個特定的問題和主題？

You know, Daniel, thank you very much. I spoke too much this morning and I'm very happy allowing my colleagues to have speaked, and I'll let David take this question.

你知道，丹尼爾，非常感謝你。今天早上我說得太多了，我很高興讓我的同事們發言，我會讓大衛回答這個問題。

Thank you. Hello David.

謝謝。你好大衛。

Thank you for the question. You're right, there is not so many companies that are very active in the cell and gene. And as you mentioned, exosome as well, it's a very interesting and attractive technology for partners. And as you said, we are, again, there're very few that have this level of development in phase 3 which of the potential to really bring treatment to patients. So to your point, the three elements, the cell and gene interest, the exosome and the fact that there is the large set of data and a unique set of biomarkers makes does our company and our data interesting and attractive to other partners. So it has always been part of our strategy has always been in discussion with potential partners, and we take that into account for the future. Thank you.

感謝你的提問。沒錯，在細胞和基因方面非常活躍的公司並不多。正如你提到的，外泌體也是一項對合作夥伴來說非常有趣和有吸引力的技術。正如你所說，我們再次強調，在第 3 階段具有這種發展水平的人很少，有可能真正為患者帶來治療。因此，就您的觀點而言，這三個要素，細胞和基因興趣，外泌體以及存在大量數據和一組獨特的生物標誌物的事實使我們的公司和我們的數據對其他合作夥伴變得有趣和有吸引力。因此，它一直是我們戰略的一部分，一直在與潛在合作夥伴進行討論，我們會在未來考慮到這一點。謝謝。

Thank you so much. And Chaim, I don't know if you could comment about how Brainstorm is thinking about it.

太感謝了。 Chaim，我不知道你是否可以評論一下 Brainstorm 是如何考慮它的。

I can only agree with David. I think he hit it.

我只能同意大衛的觀點。我認為他擊中了它。

And just lastly, given the amount of time that is now lapsed and ever increasingly growing impatience amongst ALS patients and patient advocates, some might question the motivations of Brainstorm and the team. Just curious if anyone on the Brainstorm team or anyone from their family has ever personally been impacted by ALS? And if so, would they be willing to share a little and how that experience has affected their outlook and perspective on ALS and the urgency?

最後，考慮到現在已經過去了很多時間，並且 ALS 患者和患者倡導者越來越不耐煩，有些人可能會質疑 Brainstorm 和團隊的動機。只是好奇 Brainstorm 團隊中的任何人或他們的家人是否曾經受到 ALS 的個人影響？如果是這樣，他們是否願意分享一點，以及這種經歷如何影響他們對 ALS 和緊迫性的看法和看法？

That's a very personal question. More than one of the senior management do have family members that had ALS. I can tell you that. So yes, the urgency is very high. I think that's what I was just hoping I don't think my colleagues wanted to talk to it at this point.

這是一個非常私人的問題。不止一位高級管理人員的家人患有肌萎縮側索硬化症。我可以告訴你。所以是的，緊迫性非常高。我想這就是我希望的，我認為我的同事此時不想談論它。

Okay, great. Thank you so much, Chaim and thank you to the Brainstorm team. I'll jump back in queue.

好的，太好了。非常感謝 Chaim，也感謝 Brainstorm 團隊。我會跳回到隊列中。

Thank you so much.

太感謝了。

Thank you. [Chris Msurphy], private investor. [Chris], please ask your question.

謝謝。 [Chris Msurphy]，私人投資者。 [克里斯]，請問你的問題。

Alright, sure. Based upon the successful data from the phase 2 progressive MS trial, I guess my question is, is Brainstorm in preparation for a phase 3 trial upon the publication of the phase 2 data? And if so, are you able to give a timeline on that?

好的，當然。基於 2 期進展性 MS 試驗的成功數據，我想我的問題是，Brainstorm 是否在 2 期數據公佈後準備 3 期試驗？如果是這樣，你能給出一個時間表嗎？

Thank you very much, [Chris]. I'll allow Ralph to answer your question.

非常感謝，[克里斯]。我會讓拉爾夫回答你的問題。

Yeah. Hi, [Chris]. Thanks for the question. As I mentioned earlier, we are awaiting the publication in peer-reviewed journal. I think that the peer review is the important next step, pivot step for us to make internal decisions. And once that happens, we'll discuss it. We obviously are -- we've stated that our first priority is to advance NurOwn and ALS, and we continue to be fully focused on that, but we do have a lot of support from the scientific community in our MS projects. We also plan to have very extensive scientific meetings in June and throughout the summer. And then in fall with the MS scientific community. Brainstorm is part of the International Progressive MS Alliance. And the conversations are really quite rich, and these will help us make that decision. But again, until we get to the point where the phase 2 study is published, we won't be able to make any further public statements. And thanks for the question.

是的。嗨，[克里斯]。謝謝你的問題。正如我之前提到的，我們正在等待同行評審期刊的發表。我認為同行評審是重要的下一步，是我們做出內部決策的關鍵步驟。一旦發生這種情況，我們將進行討論。我們顯然是——我們已經聲明我們的首要任務是推進 NurOwn 和 ALS，我們將繼續完全專注於此，但我們的 MS 項目確實得到了科學界的大力支持。我們還計劃在 6 月和整個夏季舉行非常廣泛的科學會議。然後與 MS 科學界合作。 Brainstorm 是國際進步 MS 聯盟的一部分。對話真的很豐富，這些將幫助我們做出決定。但同樣，在我們到達第二階段研究發表之前，我們將無法發表任何進一步的公開聲明。謝謝你的提問。

Thank you so much.

太感謝了。

Okay. We appear to have no more questions in the queue. So I will hand back to Chaim for closing remarks.

好的。隊列中似乎沒有其他問題了。所以我將把結束語交還給 Chaim。

Thank you so much [Jennie], for handling this call and thank you, everyone, for listening again. And I'll see you soon and hope to have in the next Q. It is going to be -- I'm sure this time it's not going to be in six weeks from now. It's going to be a longer stretch, technically and legally. Thank you very, very much.

非常感謝 [Jennie] 處理這個電話，感謝大家再次聆聽。我很快就會見到你，希望在下一個問題中見到你。這將是——我確信這次不會在六週後。從技術上和法律上來說，這將是一個更長的時間。非常非常感謝你。

Thank you. Ladies and gentlemen, this does conclude today's conference call. You may now disconnect your phone lines and have a wonderful day. Thank you for your participation.

謝謝。女士們，先生們，今天的電話會議到此結束。您現在可以斷開電話線並度過美好的一天。感謝您的參與。