Brainstorm Cell Therapeutics Inc (BCLI) 2025 Q1 法說會逐字稿

Greetings and welcome to the Brainstorm Cell Therapeutics first-quarter 2025 conference call. At this time, all participants are on a listen-only mode. As a reminder, this call is being recorded. I would now like to introduce your host for today's call, Joyce Lonergan of LifeSci Advisors. Joyce, you may begin.

大家好，歡迎參加 Brainstorm Cell Therapeutics 2025 年第一季電話會議。此時，所有參與者都處於只聽模式。提醒一下，本次通話正在錄音。現在我想介紹今天的電話會議主持人，LifeSci Advisors 的 Joyce Lonergan。喬伊斯，你可以開始了。

Thank you, Holly. Good morning and thank you for joining us today.

謝謝你，霍莉。早安，感謝您今天加入我們。

Before passing the call to company management for prepared remarks, I would like to remind listeners that this conference call will contain numerous statements, descriptions, forecasts, and projections regarding Brainstorm Cell Therapeutics, and its potential future business operations and performance, statements regarding the market potential for the treatment of neurodegenerative disorders such as ALS; the sufficiency of the company's existing capital resources for continuing operations in 2025 and beyond; the safety and clinical effectiveness of 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. 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.

在將電話轉給公司管理層徵求準備好的評論之前，我想提醒聽眾，本次電話會議將包含有關 Brainstorm Cell Therapeutics 及其未來潛在業務運營和業績的大量聲明、描述、預測和預測，有關治療 ALS 等神經退行性疾病的市場潛力的聲明；公司現有資本資源是否足以維持 2025 年及以後的持續運營；Nurn 平台的持續運營和臨床技術；的臨床試驗以及相關臨床開發計劃；以及公司發展策略合作和夥伴關係以支持其業務規劃工作的能力。前瞻性陳述受多種風險和不確定性的影響，其中許多超出了 Brainstorm 的控制範圍，包括其在 SEC 文件中不時描述的風險和不確定性。該公司的業績可能與今天電話會議上預測的業績有重大差異。該公司不承擔公開更新任何前瞻性聲明的義務。

Joining us on the call today will be Chaim Lebovits, President and Chief Executive Officer of Brainstorm; Dr. Haro Hartounian, Executive Vice President and Chief Operating Officer; Dr. Bob Dagher, Executive Vice President and Chief Medical Officer; and Dr. Netta Blondheim-Shraga, Senior Vice President of Research and Development.

今天參加電話會議的有 Brainstorm 總裁兼執行長 Chaim Lebovits、執行副總裁兼營運長 Haro Hartounian 博士、執行副總裁兼首席醫療官 Bob Dagher 博士和研發高級副總裁 Netta Blondheim-Shraga 博士。

I would now like to turn the call over to Mr. Lebovits. Please go ahead.

現在我想把電話轉給萊博維茨先生。請繼續。

Thank you, Joyce. Good morning or good afternoon, everyone. Thank you for joining us today. We appreciate your continued interest in supporting Brainstorm. We published our Q1 2025 earnings release after the market closed last Thursday, and colleagues and I are pleased to provide a corporate update today.

謝謝你，喬伊斯。大家早安或下午好。感謝您今天加入我們。我們感謝您一直以來對 Brainstorm 的支持。我們在上週四股市收盤後發布了 2025 年第一季財報，我和同事很高興今天提供公司最新消息。

Our unwavering primary focus remains the execution of the clinical development plan for NurOwn and the initiation of our pivotal Phase 3b trial designed to confirm its therapeutic benefit for individuals in the early stages of ALS. Hopefully, you will have seen the press release released this morning announcing that the U.S. FDA has cleared us to initiate the trial. This follows the amendments we submitted to our investigational new drug application which included comprehensive technical transfer documentation, robust quality assurance, and stringent quality control processes. This regulatory clearance marks a significant milestone, bringing us closer to commencing patient enrollment.

我們堅定不移的首要重點仍然是執行 NurOwn 的臨床開發計劃和啟動關鍵的 3b 期試驗，旨在確認其對早期 ALS 患者的治療益處。希望您已經看到了今天早上發布的新聞稿，宣布美國 FDA 已批准我們啟動試驗。這是我們對新藥研究申請提交的修改之後的結果，其中包括全面的技術轉移文件、強有力的品質保證和嚴格的品質控制流程。此次監管部門的批准標誌著一個重要的里程碑，使我們更接近開始病患招募。

As previously disclosed, the trial design has been carefully agreed upon with the FDA under a special protocol assessment or SPA. This SPA is a crucial element, as we believe it substantially de-risks the regulatory pathway for NurOwn. It provides confirmation that the trial's endpoints and our statistical analysis plan are deemed appropriate for the FDA to potentially support approval contingent upon the trial meeting its pre-specified expectations.

如前所述，試驗設計已根據特殊方案評估或 SPA 與 FDA 進行了仔細商定。這份 SPA 至關重要，因為我們相信它大大降低了 NurOwn 的監管途徑風險。它證實了試驗的終點和我們的統計分析計劃被認為適合 FDA，因此在試驗達到其預先指定的預期的情況下，FDA 可能會支持批准。

We also announced previously that in a face-to-face Type C meeting, we had achieved alignment with the FDA and CMC, a particularly vital aspect for an advanced cell therapy like NurOwn. Our CMC team is always advancing its development and continues to work as regulatory guidance directs.

我們先前也宣布，在一次面對面的 C 類會議中，我們已與 FDA 和 CMC 達成一致，這對於像 NurOwn 這樣的先進細胞療法來說是一個特別重要的方面。我們的 CMC 團隊始終致力於推進其發展，並繼續按照監管指導開展工作。

To provide further detail on our operational readiness for the upcoming trial, I'd like to turn the call over to our Chief Operating Officer, Dr. Haro Hartounian. Haro?

為了進一步詳細說明我們為即將進行的試驗所做的營運準備情況，我想將電話轉給我們的營運長 Haro Hartounian 博士。哈羅？

Thank you, Chaim. As previously discussed, we plan to initiate our initial manufacturing for the Phase 3b trial at the Tel Aviv Sourasky Medical Center. To scale up our manufacturing capabilities, we'll then proceed with the technology transfer to Pluri, which will provide additional clean room facilities. We have signed a letter of intent with Pluri and anticipate moving forward to a definitive contract soon. Furthermore, the team and I have secured a leading U.S. clinical site that has successfully passed FDA inspection. We are in the process of finalizing an LOI and we'll be announcing the details of this important site shortly. We are all very excited about the progress and remain hopeful that we can begin treating patients soon. Back to you, Chaim.

謝謝你，Chaim。如前所述，我們計劃在特拉維夫索拉斯基醫療中心啟動 3b 期試驗的初始製造。為了擴大我們的製造能力，我們將繼續向 Pluri 進行技術轉讓，Pluri 將提供額外的無塵室設施。我們已經與 Pluri 簽署了意向書，並預計很快將達成最終合約。此外，我和我的團隊已獲得一個已成功通過 FDA 檢查的美國領先臨床站點。我們正在敲定意向書 (LOI)，並將很快公佈這一重要地點的詳細資訊。我們都對這項進展感到非常興奮，並且仍然希望能夠很快開始治療患者。回到你這裡，Chaim。

Thank you, Haro, for that important update on our manufacturing and site selection progress.

感謝 Haro 提供有關我們製造和選址進展的重要更新。

Currently, we are actively engaged in negotiations for the clinical trial agreements with approximately 15 leading clinical centers across the United States, each poised to serve as a site for a Phase 3b trial. The strong interest we are getting from numerous renowned ALS clinicians and researchers underscores their conviction in the potential of NurOwn. We will make announcements regarding these agreements as they are finalized.

目前，我們正在積極與美國約 15 個領先的臨床中心進行臨床試驗協議談判，每個中心都準備好作為 3b 期試驗的地點。眾多知名 ALS 臨床醫生和研究人員表現出的濃厚興趣凸顯了他們對 NurOwn 潛力的信心。這些協議最終確定後，我們將予以公告。

As noted in our earnings press release, the details of the trial, which we are calling ENDURANCE, have now been posted on clinicaltrials.gov. On this website, you will see the study plan including primary and secondary endpoints, as well as a list of clinical sites that we expect will participate. Publication of these details is important for transparency and allows the medical community and mainly ALS patients who are interested in participating, as well as caregivers, to review the structure of the study.

正如我們在收益新聞稿中所述，這項名為「ENDURANCE」的試驗的詳細資訊現已發佈在clinicaltrials.gov網站上。在這個網站上，您可以看到研究計劃，包括主要和次要終點，以及我們預計參與的臨床試驗機構清單。公佈這些細節對於透明度來說很重要，並允許醫學界和主要有興趣參與的 ALS 患者以及護理人員審查研究的結構。

We fully recognize the urgency felt by patients and clinicians for innovative therapeutic options in ALS. Our commitment is absolute in executing this trial with the highest level of scientific rigor. With the limited treatment options currently available for ALS patients, we firmly believe that NurOwn, if successful in the study and subsequently approved, holds the promise of becoming a significant and valuable treatment.

我們充分認識到患者和臨床醫生對 ALS 創新治療方案的迫切需求。我們絕對致力於以最高水準的科學嚴謹性執行此次試驗。由於目前 ALS 患者的治療選擇有限，我們堅信，如果 NurOwn 在研究中取得成功並隨後獲得批准，它有望成為一種重要且有價值的治療方法。

In parallel with our dedicated NurOwn development efforts, our scientific team remains actively engaged with the academic community and our industry peers sharing the latest data and insights. Last week, we participated in the annual ALS Drug Development summit in Boston. A crucial gathering that brought together over 200 scientific leaders to address the most pressing challenges in the therapeutic development for this devastating disease. The discussions at this year's meeting were centered on critical areas such as target validation, the effective utilization of biomarkers, and the optimization of clinical trial design.

在我們致力於 NurOwn 開發工作的同時，我們的科學團隊積極與學術界和業內同行分享最新的數據和見解。上週，我們參加了在波士頓舉行的年度 ALS 藥物開發高峰會。這是一次重要的會議，匯集了 200 多位科學領袖，共同應對這種毀滅性疾病的治療發展中最緊迫的挑戰。今年會議的討論集中在目標驗證、生物標記的有效利用以及臨床試驗設計的最佳化等關鍵領域。

I want to take a moment to speak about our incredible team at Brainstorm. Despite facing significant financial constraints, a reality for many small biotech companies in the current environment, their dedication and tireless efforts are truly remarkable. We heard a very powerful message at the ALS Summit from Wendy, a courageous individual living with ALS, who eloquently referred to every ALS patient as a warrior.

我想花點時間談談 Brainstorm 的優秀團隊。儘管面臨著巨大的財務限制（這是當前環境下許多小型生物技術公司的現實），但他們的奉獻精神和不懈努力確實令人驚嘆。在 ALS 高峰會上，我們聽到了一位勇敢的 ALS 患者溫迪所傳達的非常有力的信息，她雄辯地將每一位 ALS 患者稱為戰士。

At Brainstorm, we see it as part of our mission to join the ranks of these warriors, working every single day to advance preparations for the critical trial. We are succeeding in making substantial progress with the limited financial resources we currently have, thanks in large to the outstanding support of our dedicated partners. This positions us to move forward with significant agility once we secure a strategic funding deal, which remains our priority.

在 Brainstorm，我們將加入這些戰士的行列視為我們使命的一部分，每天努力為關鍵審判做好準備。我們在目前有限的財政資源下取得了實質進展，這在很大程度上要感謝我們忠誠的合作夥伴的出色支持。一旦我們達成策略融資協議，我們就能以極大的靈活性向前邁進，這仍然是我們的首要任務。

We understand that members of the investment community and the ALS community are eager to know precisely when the first patient will be enrolled. Please note that our focus remains squarely and diligently completing the necessary steps, including securing adequate funding as we are working to advance various funding opportunities that include potential strategic investments and non-dilutive grants. We are simultaneously proceeding on many fronts to be able to initiate the trial as swiftly and as responsibly as possible. We are deeply committed to this endeavor, and we will continue to provide updates as they become available.

我們了解投資界和 ALS 界的成員都渴望知道第一位患者的特定入組時間。請注意，我們的重點仍然是認真完成必要的步驟，包括確保充足的資金，因為我們正在努力推進各種融資機會，包括潛在的策略性投資和非稀釋性補助金。我們正在多方面同時推進，以便能夠盡可能迅速、負責任地啟動審判。我們堅定地致力於這項努力，並將繼續提供最新更新。

I will now turn the call over to Dr. Bob Dagher, Brainstorm's Chief Medical Officer, who will give a brief summary of his presentation at the ALS Summit last week. Bob?

現在我將把電話轉給 Brainstorm 的首席醫療官 Bob Dagher 博士，他將簡要總結他在上週 ALS 峰會上的演講。鮑伯？

Thank you, Chaim. Hi everyone. As part of my presentation last week, I provided a detailed overview of the design of our planned Phase 3b trial and explained the significant changes we made versus our prior Phase 3 trial in order to increase the probability of success.

謝謝你，Chaim。大家好。作為上週演講的一部分，我詳細概述了我們計劃的 3b 期試驗的設計，並解釋了我們與之前的 3 期試驗相比所做的重大改變，以增加成功的可能性。

As we have previously disclosed, the new trial will be conducted in two parts. Part A is a 24-week double-blind period which will be followed by Part B, a 24-week open-label extension designed to evaluate long-term effects on survival and biomarkers. We have set the entry criteria to enroll patients who have early-stage ALS. In other words, those with less advanced level of functional decline.

正如我們之前所揭露的，新的審判將分兩部分進行。A 部分是 24 週的雙盲期，隨後是 B 部分，即 24 週的開放標籤延伸，旨在評估對生存和生物標記的長期影響。我們已經制定了招募早期 ALS 患者的入選標準。換句話說，就是那些功能衰退程度較輕的人。

The primary endpoint will be the change from baseline to week 24, so at the end of Part A, in the ALSFRS-R total score, which is now considered the gold standard in recent registrational trials. The results from Part A at 24 weeks, if they meet our expectations, should be sufficient to support a new BLA. This is covered specifically in our SPA agreement with the FDA.

主要終點是從基線到第 24 週的變化，即 A 部分結束時的 ALSFRS-R 總分，現在被認為是最近註冊試驗中的黃金標準。如果 24 週時 A 部分的結果符合我們的預期，則足以支持新的 BLA。我們與 FDA 簽訂的 SPA 協議中明確規定了這一點。

In the Phase 3b trial, we eliminated the three-month running period from the previous study and also shortened the screening period from 20 weeks to now 9 weeks to minimize changes between screening and baseline.

在 3b 期試驗中，我們取消了先前研究中的三個月運行期，並將篩選期從 20 週縮短到現在的 9 週，以盡量減少篩選和基線之間的變化。

I will now turn the call over to my colleague, Dr. Blondheim-Shraga, to discuss the ALS biomarkers analysis. Netta?

現在我將把電話轉給我的同事 Blondheim-Shraga 博士，討論 ALS 生物標記分析。內塔？

Thank you, Bob. My presentation at the ALS Summit focused on biomarkers in ALS and specifically, how the experiments we have conducted with biomarkers support the potential multimodal mechanism of action of NurOwn.

謝謝你，鮑伯。我在 ALS 高峰會的演講重點關注了 ALS 中的生物標誌物，特別是我們利用生物標記進行的實驗如何支持 NurOwn 的潛在多模式作用機制。

There is currently no established universal marker for ALS, as it is a complex disease that may require combinations of biomarkers for accurate assessment. We hypothesize that NurOwn exerts its biological effects across multiple pathways. Analysis of CSF samples from patients who participated in the prior Phase 3a study provided us with valuable insight into how NurOwn may be exerting its effect.

目前尚無針對 ALS 的既定通用標記，因為它是一種複雜的疾病，可能需要結合多種生物標記才能進行準確評估。我們假設 NurOwn 透過多種途徑發揮其生物學效應。對參與先前 3a 期研究的患者的腦脊髓液樣本進行分析，為我們了解 NurOwn 如何發揮其作用提供了寶貴的見解。

CSF samples were collected at seven time points from all participants in the study, and analysis of these samples showed significant changes in biomarkers that are relevant to ALS pathology. Treatment with NurOwn was associated with a reduction in neuroinflammatory and neurodegenerative biomarkers and with increase in anti-inflammatory and neuroprotective biomarkers.

研究中所有參與者在七個時間點收集了腦脊髓液樣本，對這些樣本的分析顯示與 ALS 病理相關的生物標記發生了顯著變化。NurOwn 治療與神經發炎和神經退化性生物標記的減少以及抗發炎和神經保護生物標記的增加有關。

At the ALS Summit, we presented the results from three sets of preclinical experiments to investigate the immunomodulation, neuroprotectant, and neuroregenerative properties of NurOwn. The first of these was an in vitro experimental model of immune-activated peripheral blood mononuclear cells or PBMCs that were co-cultured with neuron cells. We demonstrated that NurOwn inhibits the secretion of pro-inflammatory cytokines and decrease the proliferation of certain types of T cells, CD4 cells and CD8 cells, that are involved in the inflammatory process.

在 ALS 高峰會上，我們展示了三組臨床前實驗的結果，以研究 NurOwn 的免疫調節、神經保護和神經再生特性。其中第一個是與神經元細胞共培養的免疫活化週邊血單核細胞或 PBMC 的體外實驗模型。我們證明 NurOwn 可以抑制促發炎細胞因子的分泌，並減少參與發炎過程的某些類型的 T 細胞、CD4 細胞和 CD8 細胞的增殖。

The second was an in vitro hypoxia model that examined the effect of NurOwn on a motor neuron cell line that had been subjected to hypoxic stress in a low oxygen environment and resulted in about 1 in 3 cells dying. We showed here that when these cells were co-cultured with conditioned media collected from neuron cell cultures, viability was restored to 96.5% of normoxic conditions or 96.5% of normal, providing evidence of a neuroprotective effect.

第二個是體外缺氧模型，用於研究 NurOwn 對運動神經元細胞系的影響，該細胞系在低氧環境下受到缺氧應激，導致約三分之一的細胞死亡。我們在此表明，當這些細胞與從神經元細胞培養物中收集的條件培養基共培養時，活力恢復到常氧條件的 96.5％ 或正常的 96.5％，提供了神經保護作用的證據。

Finally, we studied an experimental neurite outgrowth model in which human neuroblastoma cells were co-cultured in a no-contact transwell system with neuron cells. We showed that NurOwn enhanced growth of neurites, supporting a neuroregenerative role for NurOwn.

最後，我們研究了一種實驗性神經突生長模型，其中人類神經母細胞瘤細胞與神經元細胞在非接觸式 Transwell 系統中共培養。我們證明 NurOwn 增強了神經突的生長，支持了 NurOwn 的神經再生作用。

As disclosed previously, we reviewed the clinical utility of neurofilament light or NFL as a biomarker of disease progression and treatment monitoring in ALS. Ten patients, who completed the prior Phase 3 trial, enrolled in an open-label expanded access program that spanned two 28-week periods. We showed that early treatment with NurOwn resulted in greater reductions in NFL levels. Among the six participants who received NurOwn in both Phase 3and the EAP, a continual group level reduction in NFL was observed.

如前所述，我們回顧了神經絲輕鍊或 NFL 作為 ALS 疾病進展和治療監測的生物標記的臨床實用性。完成先前第 3 階段試驗的 10 名患者參加了為期兩個 28 週的開放標籤擴展獲取計畫。我們證明，早期使用 NurOwn 治療可以大幅降低 NFL 水平。在第 3 階段和 EAP 中接受 NurOwn 治療的六名參與者中，觀察到 NFL 的群體水準持續下降。

In contrast, for the four patients who received placebo in the Phase 3, the group median NFL change was higher at the end of the study, indicating worsening neurodegeneration. After these patients switched to neuron in the EAP, the majority showed a stabilization in NFL levels. As these results were from a very small group, we view them as hypothesis generating and will continue to explore long term effects of treatment in our upcoming Phase 3b study.

相較之下，對於在第三階段接受安慰劑治療的四名患者，研究結束時該組的中位 NFL 變化較高，顯示神經退化性病變正在惡化。在這些患者轉換為 EAP 中的神經元後，大多數患者的 NFL 水平都趨於穩定。由於這些結果來自一個非常小的群體，我們將其視為假設生成，並將在即將進行的 3b 期研究中繼續探索治療的長期效果。

At the conference, we also shared results from a genetic substudy conducted during our Phase 3 study. We have examined the underlying genetics of ALS and how it may determine the clinical response to NurOwn. We are particularly interested in a gene called UNC13A which has been widely studied in ALS. Patients who were enrolled in the prior Phase 3 trial had the option to participate in a genetic substudy, and 124 consented.

在會議上，我們也分享了我們第三階段研究期間進行的基因亞組研究的結果。我們研究了 ALS 的潛在遺傳學以及它如何決定對 NurOwn 的臨床反應。我們對一種名為 UNC13A 的基因特別感興趣，該基因在 ALS 中得到了廣泛的研究。參加先前 3 期試驗的患者可以選擇參加基因子研究，其中 124 人同意了。

We showed in these patients that the UNC13A, the UNC13A genotype, appeared to influence the response to NurOwn therapy. Patients who were heterozygous carriers of a risk allele had a statistically significant response rate to NurOwn treatment compared with placebo, supporting further investigation of the UNC13A and other genetic factors and their correlation to treatment effect of NurOwn in our next trial.

我們在這些患者身上發現，UNC13A，即 UNC13A 基因型，似乎會影響對 NurOwn 療法的反應。與安慰劑相比，攜帶風險等位基因雜合子的患者對 NurOwn 治療的反應率具有統計上顯著的差異，這支持我們在下一次試驗中進一步研究 UNC13A 和其他遺傳因素及其與 NurOwn 治療效果的相關性。

I will now turn the call back to Chaim for closing comments.

現在我將把電話轉回給 Chaim 進行最後發言。

Thank you, Netta.

謝謝你，Netta。

For the details on Brainstorm's financials for the quarter ended March 31, 2025, I will refer you to the press release we issued on Thursday and also to our 10-Q filed with the SEC.

有關 Brainstorm 截至 2025 年 3 月 31 日的季度財務狀況的詳細信息，請參閱我們週四發布的新聞稿以及我們向美國證券交易委員會提交的 10-Q 報表。

We're now ready for the Q&A. Joyce?

我們現在準備好進行問答了。喬伊斯？

Thank you, Chaim. We have four written questions. The first one, can you start the trial without proper funding?

謝謝你，Chaim。我們有四個書面問題。第一個問題，沒有足夠的資金可以開始試驗嗎？

Thank you. That's a very good question. While our financials over the past year and a half have reflected a very challenging environment. We have nonetheless been able to make significant strides in preparing for the trial, including technology transfer, FDA regulatory submissions, site selections, and CRO engagements. However, initiating and successfully executing a clinical trial of this nature demands a robust and sustainable cash flow. Therefore, while we have diligently progressed to this point with relatively limited resources, securing proper funding is an essential to commence the trial.

謝謝。這是一個非常好的問題。過去一年半我們的財務狀況反映出了一個非常具有挑戰性的環境。儘管如此，我們在試驗準備方面已經取得了重大進展，包括技術轉移、FDA 監管提交、場地選擇和 CRO 合作。然而，啟動並成功執行這種性質的臨床試驗需要強勁且可持續的現金流。因此，雖然我們在資源相對有限的情況下努力取得了這一進展，但獲得適當的資金對於開始試驗至關重要。

As communicated in our recent press release, we are actively pursuing multiple funding avenues to ensure the timely commencement of the trial. These efforts are in various stages, encompassing a promising $15 million non-dilutive grant currently will be under review, alongside ongoing negotiations for strategic partnerships. We are focusing on strategic partnerships. Our priority is to secure the necessary capital through such partnerships to confidently initiate and complete this study.

正如我們最近的新聞稿中所述，我們正在積極尋求多種融資管道，以確保試驗及時開始。這些努力處於不同階段，包括一項有希望的 1500 萬美元非稀釋性贈款，目前正在接受審查，同時正在進行戰略合作夥伴關係的談判。我們注重策略夥伴關係。我們的首要任務是透過這種合作關係確保必要的資金，以便自信地啟動和完成這項研究。

Thank you, Chaim. We have a second question. We see you call the trial ENDURANCE. What's the meaning of that?

謝謝你，Chaim。我們還有第二個問題。我們看到您將這次試驗稱為「耐力」。那是什麼意思？

Thank you for that. The name ENDURANCE was carefully chosen to deeply resonate with ALS community. It stands as a tribute to the remarkable strength, tenacity, and unwavering spirit demonstrated by individuals living with ALS and their families.

謝謝你。ENDURANCE 這個名字是經過精心挑選的，以便與 ALS 社區產生深刻共鳴。它向 ALS 患者及其家人所表現出的非凡力量、毅力和堅定不移的精神致敬。

For Brainstorm, ENDURANCE also underscores our steadfast commitment to persevere in our scientific endeavors and generate the robust data required for regulatory approval of NurOwn. We believe that this trial embodies the collective resilience of patients and our determined mission to deliver a potentially meaningful therapeutic option for ALS. Thank you.

對於 Brainstorm 而言，ENDURANCE 也強調了我們堅定不移地致力於堅持科學探索並產生 NurOwn 監管批准所需的可靠數據。我們相信，這項試驗體現了患者的集體韌性以及我們為 ALS 提供潛在有意義的治療選擇的堅定使命。謝謝。

Thank you for that, Chaim. The third question is, will the company also be producing in the U.S.?

謝謝你，Chaim。第三個問題是，該公司也會在美國生產嗎？

Thank you. Haro, you want to take that?

謝謝。哈羅，你想拿走那個嗎？

Sure. Thank you so much for the question. Absolutely, expanding our manufacturing footprint to the United States is a key strategic objective for us. We're pleased to share that we will be announcing a letter of intent in the coming days with the U.S.-based facility that has a proven track record, having already successfully passed FDA inspection for the production of other products. This signifies an important step in our plans for future commercialization and supply chain security.

當然。非常感謝您的提問。當然，將我們的製造足跡擴展到美國是我們的關鍵策略目標。我們很高興地告訴大家，我們將在未來幾天內與這家位於美國的工廠簽署一份意向書，該工廠擁有良好的業績記錄，並且已經成功通過了 FDA 對其他產品生產的檢查。這標誌著我們未來商業化和供應鏈安全計畫邁出了重要一步。

Thank you.

謝謝。

Thank you for that. Question four is, can you update on any advances in the exosome program or are you not proceeding with that at this time?

謝謝你。第四個問題是，您能否更新外泌體計劃的任何進展，或者您目前沒有繼續進行該計劃？

Thank you. Netta, please take that one.

謝謝。內塔，請拿著這個。

Sure. Thank you for this question. We are highly encouraged by the progress of our exosome program as the field of exosome-based therapeutics continues to show strong potential in the treatment of respiratory and inflammatory diseases. Our proprietary allogeneic exosome platform has yielded promising preclinical data demonstrating both therapeutic and preventative effects and models of lung disease.

當然。感謝您的提問。我們的外泌體計畫的進展令我們感到非常鼓舞，因為基於外泌體的治療領域在呼吸系統和發炎疾病的治療中繼續顯示出強大的潛力。我們專有的同種異體外泌體平台已經產生了有希望的臨床前數據，證明了肺部疾病的治療和預防效果和模型。

To support these findings, we are preparing a manuscript detailing the efficacy of our exosomes in a preclinical model of COPD which would join our existing publication about the efficacy of exosomes in a model of ARDS. Together, these works outline the wide potential of our allogeneic exosome technology, which is derived from neuron cells. Briefly, our new findings demonstrate that early treatment with exosomes significantly reduces lung inflammation in response to bleomycin, as a chemotherapy agent with known lung toxicity, and significantly reduced lung fibrosis two weeks later compared to untreated controls.

為了支持這些發現，我們正在準備一份手稿，詳細說明我們的外泌體在 COPD 臨床前模型中的功效，該手稿將加入我們現有的關於外泌體在 ARDS 模型中的功效的出版物。總之，這些研究概述了我們的源自神經元細胞的同種異體外泌體技術的廣泛潛力。簡而言之，我們的新發現表明，早期使用外泌體治療可顯著減少對博來黴素（一種已知具有肺毒性的化療藥物）的反應性肺部炎症，並且與未經治療的對照組相比，兩週後可顯著減少肺纖維化。

In light of these exciting new results, we are actively pursuing strategic partnerships to advance the exosome program towards clinical development. In parallel, we are expanding our global intellectual property portfolio and anticipate announcing the issuance of additional patents that will further strengthen the protection of our innovations.

鑑於這些令人興奮的新成果，我們正在積極尋求策略合作夥伴關係，以推動外泌體計劃走向臨床開發。同時，我們正在擴大我們的全球智慧財產權組合，並預計將宣布頒發更多專利，以進一步加強對我們創新的保護。

Thank you, Netta. Holly, could you open the line for one or two questions?

謝謝你，Netta。荷莉，您能打開熱線回答一兩個問題嗎？

(Operator Instructions)

（操作員指示）

Jason McCarthy, Maxim Group.

傑森麥卡錫，馬克西姆集團。

Good morning, everybody. Thanks for taking the questions. If you can go back to the UNC13A discussion that you're having, have you had any communications with FDA in terms of being able to stratify by UNC13A in the upcoming Phase 3b? Or was that association that you showed through the EAP more of an exploratory study. Are you locked in with the SPA, you don't really have a lot of wiggle room around the ALSFRS to go for UNC13A stratification as well?

大家早安。感謝您回答這些問題。如果您可以回顧正在進行的 UNC13A 討論，您是否與 FDA 進行過任何溝通，以便在即將到來的第 3b 階段根據 UNC13A 進行分層？或者您透過 EAP 展示的關聯性更像是一項探索性研究。您是否被 SPA 鎖定，在 ALSFRS 周圍是否真的沒有太多迴旋餘地來進行 UNC13A 分層？

Thank you very much for that question, Jason. In general, the FDA is not yet approving any biomarker as a surrogate, but I would like Bob to elaborate more on that, Bob.

非常感謝你的提問，傑森。總體而言，FDA 尚未批准任何生物標記作為替代品，但我希望 Bob 對此進行更詳細的說明，Bob。

Oh yeah. Thank you, Jason, for the question. So under the special protocol assessment agreement with the FDA, the protocol, wouldn't use the word lock, but It's agreed on with all the details, including the population. It's not impossible or difficult to go and add and make changes which will require obviously discussions. However, scientifically speaking, and we're very excited with the larger ALS community about these new genetic discoveries and the UNC13A story is evolving. However, it remains exploratory and not definitive at this stage in the game of the trial design innovations, et cetera.

哦，是的。謝謝傑森提出的問題。因此，根據與 FDA 達成的特殊協議評估協議，該協議不會使用「鎖定」一詞，但已就包括人口在內的所有細節達成協議。添加和進行更改並非不可能或困難，這顯然需要討論。然而，從科學的角度來說，我們和廣大 ALS 群體一樣對這些新的基因發現以及 UNC13A 故事的發展感到非常興奮。然而，在試驗設計創新等遊戲的現階段，它仍然處於探索階段，尚未確定。

We are acutely aware of what's going on. I presented the data on UNC13A two weeks ago in New Orleans at ISCT. It was very well received in oral presentation. It was chosen for that target audience as well. So excitement is there, but not yet at the level where it will rise to become a stratification point. However, we're going to be obviously exploring. We do post hoc analysis and we cut the populations in however many ways we need to to evaluate further the effect of NurOwn in the next study in the Phase 3b. Thank you for your question. I really appreciate it.

我們清楚地知道正在發生什麼。兩週前，我在新奧爾良的 ISCT 上展示了有關 UNC13A 的數據。口頭報告非常受歡迎。它也是針對該目標受眾而選擇的。因此，興奮是存在的，但尚未達到上升成為分層點的水平。然而，我們顯然會進行探索。我們進行了事後分析，並根據需要以多種方式縮小人群範圍，以便在第 3b 階段的下一項研究中進一步評估 NurOwn 的效果。感謝您的提問。我真的很感激。

Got it. And another, I guess, somewhat technical question. You had talked a bit about the hypoxic stress co-culture with neuron cells or the neuron media, if I caught that right. And did you say that it restored normoxic activity? And if so, could that mechanism of action be used as part of a data package when you file the BLA the next time around? Because I remember last time, a lot of questions around growth factors and levels of this and levels of that came up, but is this more defining of the mechanism of action for NurOwn that would be supportive of the next BLA.

知道了。我想，還有一個有點技術性的問題。如果我理解正確的話，您剛才談到了缺氧壓力與神經元細胞或神經元培養基的共培養。您是否說過它恢復了常氧活性？如果是這樣，那麼下次您提交 BLA 時，該作用機制是否可以作為資料包的一部分使用？因為我記得上次，有很多關於生長因素和這個水平以及那個水平的問題出現，但這是否更能定義 NurOwn 的作用機制，以支持下一個 BLA。

A very good question. Netta can answer the first part and Bob can answer the second part.

非常好的問題。Netta 可以回答第一部分，Bob 可以回答第二部分。

Thank you. Yes, you're correct. What we saw was that the media that was enriched by our cells had a protective effect and a rescue effect, really, on cells under hypoxic conditions and restored them back to almost 100% of normoxic condition. So 96.5%. This is a cell culture, so it's a simplistic model. It's not a human live model. It's not a clinical model. But it is supportive, I think, and was included in our IND as well.

謝謝。是的，你說得對。我們看到，富含我們細胞的培養基確實對缺氧條件下的細胞具有保護作用和拯救作用，並將它們恢復到幾乎 100% 的常氧狀態。所以是 96.5%。這是一種細胞培養，因此是一個簡單的模型。這不是真人模型。這不是一個臨床模式。但我認為它是支持性的，也包含在我們的 IND 中。

Got it. And just last question on the manufacturing. I know you're aiming to open up additional clean rooms, but currently, the Tel Aviv facility, how many therapies can it handle?

知道了。最後一個問題是關於製造的。我知道您打算開設更多的無塵室，但是目前，特拉維夫的設施可以處理多少療法？

It depends on how many rules we are using. It will be a rolling enrollment, as you know, with the phases (inaudible) CTSO. It will serve us for the first few months. And then we'll start with Pluri, as Haro had specified before. And I believe that next year, we'll have the U.S. site also up and running.

這取決於我們使用了多少規則。如您所知，這將是一個滾動招生，分階段（聽不清楚）CTSO。它將在最初的幾個月為我們服務。然後我們將從 Pluri 開始，正如 Haro 之前指定的那樣。我相信明年我們的美國網站也將啟動並運行。

Got it. Thanks for taking the question time.

知道了。感謝您抽空提問。

You're very welcome. We have time for one more question, Holly?

不用客氣。荷莉，我們還有時間再問一個問題嗎？

David Bautz, Zachs Small Cap.

大衛鮑茲 (David Bautz)，Zachs Small Cap。

Good morning, everyone. Thanks for the update this morning. So Chaim, I just want to make sure I heard correctly that you guys are looking to open up, is it 15 clinical trial sites? And then for each of those sites, obviously, financing aside, what needs to occur to get those sites up and running so that they can enroll patients? And then lastly, do you have any estimation of how many patients you can enroll, say, per month just based on manufacturing capacity?

大家早安。感謝您今天早上的更新。所以 Chaim，我只是想確保我沒聽錯，你們想要開放的是 15 個臨床試驗點嗎？那麼對於每個站點來說，顯然，除了資金之外，還需要做些什麼才能使這些站點啟動並運行，以便它們能夠招募患者？最後，您是否能根據生產能力估算每月可以接收多少位患者？

Yeah. Thank you very much for that question. So on clinicaltrials.gov, you will see a listing of the sites. It's out there. But we didn't yet sign the CTAs. We'll be announcing very soon gradually after we sign CTAs. And yeah, as I just mentioned, we'll start to grow side by side based on a GAAN of patient population that we're going to be enrolling based on the manufacturing. So we're working at the final steps steps of that GAAN, so I can't share exact numbers now. But the plan is, as you know, the 200-patient trial within two to three years to everyone enrolled and everyone treated at the first part and we'll be deep into the second part as well. And I want to remind you that the BLA would be filed if we have statistical significant result of the first part of the trial.

是的。非常感謝您提出這個問題。因此，在 clinicaltrials.gov 上，您將看到網站清單。它就在那裡。但我們尚未簽署 CTA。簽署 CTA 後，我們將很快逐步宣布訊息。是的，正如我剛才提到的，我們將根據製造情況招募的患者群體的 GAAN 開始並行發展。我們正在努力完成 GAAN 的最後幾個步驟，所以我現在無法分享確切的數字。但如您所知，計劃是在兩到三年內對 200 名患者進行試驗，讓每個人都參與其中，並在第一部分對每個人都進行治療，我們也將深入研究第二部分。我想提醒您，如果我們獲得試驗第一部分具有統計意義的結果，就會提交 BLA。

Okay. Great. Thanks for taking the question.

好的。偉大的。感謝您回答這個問題。

Thank you very much. I want to thank everyone for being on the call today. We're hoping to close at 9:00, I see it's exactly 9:00. Thank you very much and have a wonderful day.

非常感謝。我要感謝今天參加電話會議的各位。我們希望在 9:00 關門，我看到現在剛好是 9:00。非常感謝您，祝您有美好的一天。

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.

今天的會議到此結束。現在您可以斷開線路。感謝您的參與。