Editas Medicine Inc (EDIT) 2023 Q1 法說會逐字稿

Good morning, and welcome to Editas Medicine's First Quarter Conference Call. (Operator Instructions) Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Christi Barnett, Corporate Communications and Investor Relations at Editas Medicine.

早上好，歡迎來到 Editas Medicine 第一季度電話會議。 （操作員說明）請注意，此通話是應公司要求進行錄音的。我現在想把電話轉給 Editas Medicine 的企業傳播和投資者關係部的 Christi Barnett。

Thank you, Camilla. Good morning, everyone, and welcome to our first quarter 2023 conference call. Earlier this morning, we issued a press release providing our results and recent corporate updates. A replay of today's call will be available in the Investors section of our website approximately 2 hours after its completion.

謝謝你，卡米拉。大家早上好，歡迎來到我們 2023 年第一季度的電話會議。今天早上早些時候，我們發布了一份新聞稿，提供了我們的結果和最近的公司更新。今天的電話會議結束後大約 2 小時，我們網站的“投資者”部分將提供今天電話會議的重播。

After our prepared remarks, we will open the call for Q&A.

在我們準備好發言後，我們將打開問答環節。

As a reminder, various remarks that we make during this call about the company's future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC as updated by our subsequent filings.

提醒一下，我們在本次電話會議中就公司的未來預期、計劃和前景發表的各種評論構成了根據 1995 年《私人證券訴訟改革法》規定的安全港條款的前瞻性陳述。實際結果可能與那些存在重大差異由於各種重要因素，這些前瞻性陳述表明了這些因素，包括在我們最近的 10-K 表格年度報告的風險因素部分中討論的因素，該表格已提交給美國證券交易委員會，並在我們隨後提交的文件中進行了更新。

In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change.

此外，任何前瞻性陳述僅代表我們截至今日的觀點，不應被視為代表我們截至任何後續日期的觀點。除非法律要求，否則我們明確表示不承擔任何更新或修改任何前瞻性陳述的義務，即使我們的觀點發生變化也是如此。

Now I will turn the call over to our CEO, Gilmore O'Neill.

現在我將把電話轉給我們的首席執行官 Gilmore O'Neill。

Thank you, Christie, and good morning, everyone. Thank you for joining us today on Editas' first quarter earnings call. I'm joined today by 2 other members of the Editas executive team, Baisong Mei, our Chief Medical Officer; and Michelle Robertson, our Chief Financial Officer. As many of you know, in early January, we shared our strategy to position Editas as a leader in in vivo programmable gene editing and hemoglobinopathies. During the first quarter, we successfully executed this strategy driving to our goal of delivering life-changing medicines to patients with previously untreatable or undertreated diseases. We are increasing our momentum in driving our ex vivo EDIT-301 program as we pursue a leadership position in hematopoietic stem cell medicines for hemoglobinopathy.

謝謝克里斯蒂，大家早上好。感謝您今天加入我們參加 Editas 第一季度財報電話會議。今天，Editas 執行團隊的另外 2 名成員加入了我的行列，我們的首席醫療官 Baisong Mei；和我們的首席財務官 Michelle Robertson。正如你們許多人所知，在 1 月初，我們分享了將 Editas 定位為體內可編程基因編輯和血紅蛋白病領域領導者的戰略。在第一季度，我們成功地執行了這一戰略，推動了我們的目標，即為患有以前無法治愈或治療不足的疾病的患者提供改變生命的藥物。隨著我們在治療血紅蛋白病的造血幹細胞藥物領域取得領先地位，我們正在加大推動體外 EDIT-301 計劃的勢頭。

As a quick recap, there are 3 underlying pillars to our new strategy. First, while continuing to develop EDIT-301 for severe sickle cell disease and transfusion-dependent beta-thalassemia, or TDT, we have sharpened our discovery focus to in vivo administered genome editing medicines. As part of that refocusing effort, we previously announced that we had divested our iNK cell franchise to Shoreline Biosciences in January. Second, we are strengthening our discovery engine and technological capabilities. We have divided our research division into separate technology and drug discovery groups, enhancing the capabilities of each and implementing our new target selection criteria.

快速回顧一下，我們的新戰略有 3 個基本支柱。首先，在繼續開髮用於嚴重鐮狀細胞病和輸血依賴性β-地中海貧血（TDT）的 EDIT-301 的同時，我們將發現重點放在體內管理的基因組編輯藥物上。作為重新調整工作重點的一部分，我們之前宣布我們已在 1 月份將 iNK 細胞特許經營權出售給 Shoreline Biosciences。其次，我們正在加強我們的發現引擎和技術能力。我們已將我們的研究部門劃分為獨立的技術和藥物發現小組，增強每個小組的能力並實施我們新的目標選擇標準。

Finally, our third strategic pillar is an increase and expanded approach to business development. In tandem, we will continue to deleverage our IP portfolio to drive out-licensing and partnership discussions. So how have we executed against our new strategy in the first quarter? We have increased our investment in our EDIT-301 program after reviewing promising initial RUBY Phase I/II study data that indicated that we have a competitive and potentially differentiated program to treat sickle cell anemia and TDT. Additionally, we are investing to develop an in vivo approach for editing hematopoietic stem cells for the treatment of sickle cell disease and TDT, leveraging the unique and differentiated approach of EDIT-301 that we have already seen POC for in humans.

最後，我們的第三個戰略支柱是增加和擴展業務發展方法。同時，我們將繼續去槓桿化我們的知識產權組合，以推動對外許可和合作夥伴關係的討論。那麼我們在第一季度是如何執行我們的新戰略的呢？在審查了有希望的初始 RUBY I / II 期研究數據後，我們增加了對 EDIT-301 計劃的投資，這些數據表明我們有一個具有競爭力和潛在差異化的計劃來治療鐮狀細胞性貧血和 TDT。此外，我們正在投資開發一種體內方法來編輯造血幹細胞以治療鐮狀細胞病和 TDT，利用我們已經在人類中看到的 POC 的 EDIT-301 的獨特和差異化方法。

We continue to ramp up enrollment and dosing of patients in the RUBY trial for sickle cell disease and are on track to have dosed 20 total patients by the end of 2023. We are also excited to share that the FDA recently granted orphan drug designation to EDIT-301 for the treatment of sickle cell disease, and we are pleased to announce that, in June, we will provide a RUBY clinical data update in an oral presentation at the European Hematology Association, or EHA Congress, and in our company-sponsored webinar. Baisong will share further details regarding our June data readout and our enrollment progress in his remarks.

我們將繼續增加鐮狀細胞病 RUBY 試驗中患者的入組和劑量，並有望在 2023 年底之前完成 20 名患者的劑量。我們也很高興地與大家分享，FDA 最近授予 EDIT 孤兒藥稱號-301 用於治療鐮狀細胞病，我們很高興地宣布，6 月，我們將在歐洲血液學協會或 EHA 大會的口頭報告中以及我們公司贊助的網絡研討會上提供 RUBY 臨床數據更新.白松將在他的講話中分享有關我們 6 月份數據讀數和我們的註冊進度的更多詳細信息。

On EDIT-301 for TDT, we are pleased to share that we dosed the first patient in our EDITHAL Phase I/II trial in the first quarter and that the patient has successfully engrafted neutrophils and platelets. Enrollment continues to progress and we remain on track to provide initial clinical data from the EDITHAL trial by year-end.

關於 TDT 的 EDIT-301，我們很高興地分享我們在第一季度的 EDITHAL I / II 期試驗中給第一位患者給藥，並且該患者已成功植入中性粒細胞和血小板。招募工作繼續進行，我們仍有望在年底前提供 EDITHAL 試驗的初步臨床數據。

Moving to in vivo. Earlier this year, our drug discovery group began lead discovery work on in vivo therapeutic targets in HSCs or hematopoietic stem cells and other tissues. As a reminder, under our new target selection criteria, we will select therapeutic targets that will allow our genome editing approach to differentiate maximally from the current standard of care for serious diseases. The target selection criteria will work to ensure targets are selected that maximize the probability of technical, regulatory and commercial success.

移動到體內。今年早些時候，我們的藥物發現小組開始了 HSC 或造血幹細胞和其他組織體內治療靶點的先導發現工作。提醒一下，根據我們新的目標選擇標準，我們將選擇能夠使我們的基因組編輯方法最大程度地區別於當前嚴重疾病護理標準的治療目標。目標選擇標準將確保選擇的目標能夠最大限度地提高技術、監管和商業成功的可能性。

Our search for a new CSO to lead this drug discovery group continues to progress, and I look forward to updating you on this search and our in vivo work in the future.

我們正在尋找新的 CSO 來領導這個藥物發現小組，並繼續取得進展，我期待著為您提供有關此次搜索和我們未來體內工作的最新信息。

Turning to our intellectual property position. Since the founding of Editas, we have placed substantial importance in securing robust intellectual property protection covering our cutting-edge scientific discoveries and gene editing advancements to enable the development of novel transformative medicines for patients in need. It is important to note that we have a large portfolio of foundational U.S. and international patents covering CRISPR/Cas9 in human therapeutics, only some of which are subject to interference proceedings. And we are confident that our IP portfolio will provide meaningful value in the future. We are the exclusive licensee of Harvard University's and Broad Institute's Cas9 patent estates and Editas is uniquely positioned to issue exclusive and nonexclusive licenses for Cas9 to any company seeking to use these enzymes to make human medicines, including an in vivo and ex vivo therapeutic applications.

轉向我們的知識產權立場。自 Editas 成立以來，我們非常重視確保強有力的知識產權保護，涵蓋我們的尖端科學發現和基因編輯進展，以便為有需要的患者開發新型轉化藥物。值得注意的是，我們擁有大量涵蓋人類治療中 CRISPR/Cas9 的美國和國際基礎專利組合，其中只有一部分受到干擾訴訟。我們相信我們的知識產權組合將在未來提供有意義的價值。我們是哈佛大學和 Broad Institute 的 Cas9 專利資產的獨家被許可人，Editas 具有獨特的優勢，可以向任何尋求使用這些酶製造人類藥物（包括體內和體外治療應用）的公司頒發 Cas9 的獨家和非獨家許可。

Our unique position as the exclusive licensee of this patent estate ensures that we are the party responsible for any licensing discussions as CRISPR/Cas9 products enter the market, which, given the size of the U.S. patient market, the number of companies buying to develop CRISPR/Cas9 medicines is a substantial position. With our newly sharpened strategic focus, our world-class scientists and employees and our keen attention to execution, we continue to build upon the momentum from our clinical readout milestones during the fourth quarter of 2022. We look forward to updating you on our progress and on the execution of our new strategy throughout the year.

我們作為該專利財產的獨家被許可人的獨特地位確保我們是負責任何許可討論的一方，因為 CRISPR/Cas9 產品進入市場，考慮到美國患者市場的規模，購買開發 CRISPR 的公司數量/Cas9 藥物是一個重要的位置。憑藉我們新加強的戰略重點、我們世界一流的科學家和員工以及我們對執行的敏銳關注，我們將繼續在 2022 年第四季度臨床讀出里程碑的勢頭基礎上再接再厲。我們期待向您介紹我們的進展和最新進展全年執行我們的新戰略。

Now I will turn the call over to Baisong, our Chief Medical Officer. Baisong?

現在我將把電話轉給我們的首席醫療官白松。白松？

Thank you, Gilmore. Good morning, everyone. Let's start with EDIT-301 RUBY study for severe sickle cell disease. As Gilmore mentioned, we continue to enroll and dose patients in the RUBY study. We have activated 20 study sites and enrolled 19 patients, almost double the number of patients enrolled from 3 months ago. As we previously shared, we began parallel dosing of patients earlier this year. We are on track to provide an update on the RUBY clinical data both next month and year-end as well as to dose 22 locations by year-end.

謝謝你，吉爾摩。大家，早安。讓我們從針對嚴重鐮狀細胞病的 EDIT-301 RUBY 研究開始。正如 Gilmore 提到的，我們繼續在 RUBY 研究中招募患者並對其進行給藥。我們已經啟動了 20 個研究中心並招募了 19 名患者，幾乎是 3 個月前招募患者人數的兩倍。正如我們之前分享的那樣，我們在今年早些時候開始對患者進行平行給藥。我們有望在下個月和年底提供 RUBY 臨床數據的更新，並在年底前對 22 個地點進行給藥。

Turning to clinical data. I'm excited that we will present RUBY clinical data as an oral presentation at the European Hematology Association, or EHA Congress, and at our company-sponsored webinar in June. The data set will include safety and efficacy data for multiple patients, including 10 months data from the first patient treated and 6 months data from the second patient treated, including total hemoglobin, fetal hemoglobin. We will also share data on safety, neutrophil and platelet engraftment and vaso-occlusive events or VOE, from the first 4 patients.

轉向臨床數據。我很高興我們將在 6 月的歐洲血液學協會或 EHA 大會上以及我們公司贊助的網絡研討會上以口頭報告的形式介紹 RUBY 臨床數據。該數據集將包括多個患者的安全性和有效性數據，包括第一個接受治療的患者的 10 個月數據和第二個接受治療的患者的 6 個月數據，包括總血紅蛋白、胎兒血紅蛋白。我們還將分享前 4 名患者的安全性、中性粒細胞和血小板植入以及血管閉塞事件或 VOE 的數據。

As a reminder, last December, we presented initial data from the first 2 patients treated in the RUBY trial. The first patient who had 5 months of follow-up after treatment with EDIT-301 showed clinically significant improvements across all hematological parameters and no VOEs. Specifically, that patient had an increase of fetal hemoglobin fraction to 45.4% 5 months after EDIT-301 infusion. And the correction of anemia with total hemoglobin level well into the normal range at 16.4 grams per deciliter. These initial clinical data indicated that EDIT-301 provides patients with high and sustained level of fetal hemoglobin and normal level of total hemoglobin. This clinical observation is consistent with preclinical data, which has demonstrated that targeting of gamma-globin promoter enables increases of fetal hemoglobin independent of erythropoietic stress.

提醒一下，去年 12 月，我們提供了在 RUBY 試驗中接受治療的前 2 名患者的初步數據。第一位接受 EDIT-301 治療後進行了 5 個月隨訪的患者顯示，所有血液學參數均有臨床顯著改善，且無 VOE。具體而言，該患者在輸注 EDIT-301 後 5 個月後胎兒血紅蛋白分數增加至 45.4%。並且貧血的糾正與總血紅蛋白水平很好地進入了正常範圍，在每分升 16.4 克。這些初步臨床數據表明，EDIT-301可為患者提供高且持續的胎兒血紅蛋白水平和正常水平的總血紅蛋白。這一臨床觀察結果與臨床前數據一致，臨床前數據表明，靶向γ-珠蛋白啟動子能夠獨立於紅細胞生成應激增加胎兒血紅蛋白。

Given the unique gene-editing approach and mechanism of action by EDIT-301, supported by preclinical data and initial clinical data, we continue to believe that EDIT-301 can potentially provide robust clinical benefit to patients with severe sickle cell disease, and potentially provide clinical differentiation in the long term.

鑑於 EDIT-301 獨特的基因編輯方法和作用機制，在臨床前數據和初始臨床數據的支持下，我們仍然相信 EDIT-301 有可能為患有嚴重鐮狀細胞病的患者提供強大的臨床益處，並有可能提供長期臨床分化。

As a reminder, a sustained normal total hemoglobin level is an important clinical outcome for patients as the correction of anemia can significantly improve quality of life and ameliorate end-organ damage. We believe sustained normal level of total hemoglobin could be a potential point of differentiation for EDIT-301.

提醒一下，持續正常的總血紅蛋白水平是患者的重要臨床結果，因為糾正貧血可以顯著改善生活質量並減輕終末器官損傷。我們認為持續正常的總血紅蛋白水平可能是 EDIT-301 的潛在分化點。

Turning to EDIT-301 EDITHAL Phase I/II trial for transfusion-dependent Beta Thalassemia. As Gilmore mentioned earlier, we dosed our first patient in Q1 and the patient has successful neutrophil and platelet engraftment. We remain on track to provide initial clinical data from the EDITHAL trial by year-end. As we have done for the RUBY study, we are also taking multiple measures to accelerate the development of EDIT-301 for TDT and have strong positive momentum.

轉向 EDIT-301 EDITHAL I/II 期輸血依賴性地中海貧血試驗。正如 Gilmore 之前提到的，我們在 Q1 給第一位患者給藥，該患者成功植入了中性粒細胞和血小板。我們仍有望在年底前提供 EDITHAL 試驗的初步臨床數據。正如我們為 RUBY 研究所做的那樣，我們也正在採取多種措施加快 EDIT-301 for TDT 的開發，並具有強勁的積極勢頭。

We have enrolled multiple patients who have completed apheresis and have their CD34 positive cells edited or are in the process of apheresis. Recently, I have been traveling around the country visiting our RUBY and EDITHAL clinical trial sites. I very much appreciate the enthusiasm and the support from the investigators in study size. I'm pleased with the momentum of EDIT-301 in patient recruitment, apheresis, editing and dosing in both studies. I'm excited to hear from investigators that patients dosed with EDIT-301 have already seen positive changes in their lives. We look forward to sharing additional updates as the year progresses, including RUBY study data next month and at year-end, and sharing initial clinical data from EDITHAL study by year-end.

我們已經招募了多名已完成單採術並對其 CD34 陽性細胞進行編輯或正在進行單採術的患者。最近，我一直在全國各地訪問我們的 RUBY 和 EDITHAL 臨床試驗基地。我非常感謝研究人員對研究規模的熱情和支持。我對兩項研究中 EDIT-301 在患者招募、單採術、編輯和給藥方面的勢頭感到滿意。我很高興聽到研究人員說服用 EDIT-301 的患者已經在他們的生活中看到了積極的變化。我們期待隨著時間的推移分享更多更新，包括下個月和年底的 RUBY 研究數據，以及年底前分享 EDITHAL 研究的初步臨床數據。

Now I will turn the call over to Michelle, our Chief Financial Officer, to review our financials.

現在我將把電話轉給我們的首席財務官米歇爾，以審查我們的財務狀況。

Thank you, Baisong, and good morning, everyone. I'd like to refer you to our press release issued earlier today for a summary of our financial results for the first quarter of 2023. I'll take this opportunity to briefly review a few items. Our cash, cash equivalents and marketable securities as of March 31 were $402 million compared to $437 million as of December 31, 2022. We expect our existing cash, cash equivalents and marketable securities to fund our operating expenses and capital expenditure into 2025.

謝謝白松，大家早上好。我想請您參閱我們今天早些時候發布的新聞稿，了解我們 2023 年第一季度的財務業績摘要。我將藉此機會簡要回顧幾個項目。截至 3 月 31 日，我們的現金、現金等價物和有價證券為 4.02 億美元，而截至 2022 年 12 月 31 日為 4.37 億美元。我們預計我們現有的現金、現金等價物和有價證券將為我們的運營費用和資本支出提供資金，直至 2025 年。

Revenue for the first quarter of 2023 was $9.9 million compared to $6.8 million in the same period last year. The increase is related to the previously announced sale of our oncology assets to Shoreline Biosciences and related licenses, which was completed in January 2023. G&A expenses for the quarter was $23 million compared to $19.5 million for the first quarter of 2022. The $3.5 million increase is primarily attributable to increased professional services expenses to support business development activities, partially offset by a decrease in stock compensation expense.

2023 年第一季度的收入為 990 萬美元，而去年同期為 680 萬美元。這一增長與之前宣布的將我們的腫瘤學資產出售給 Shoreline Biosciences 及相關許可有關，該交易於 2023 年 1 月完成。本季度的 G&A 費用為 2300 萬美元，而 2022 年第一季度為 1950 萬美元。增加了 350 萬美元這主要是由於支持業務發展活動的專業服務費用增加，部分被股票補償費用的減少所抵消。

R&D expenses this quarter were $38 million, which was flat compared to the first quarter of 2022. This reflects a decrease in expenses following the strategic reprioritization of our portfolio, offset by increased investments to accelerate the development of EDIT-301. This reallocation of capital is in line with our strategic priorities.

本季度的研發費用為 3800 萬美元，與 2022 年第一季度持平。這反映出在我們對投資組合進行戰略優先排序後費用減少，但被加速 EDIT-301開發的投資增加所抵消。這種資本重新分配符合我們的戰略重點。

Overall, Editas remains in a strong financial position, and our sharpened discovery focus allowed us to concentrate our talent and extend our cash runway into 2025, which provides ample resources and support our continued progress in both of our EDIT-301 trials as well as advancing our research efforts in hemoglobinopathies and other in vivo discoveries. With that, I will hand the call back to Gilmore.

總體而言，Editas 的財務狀況仍然強勁，我們更加專注於發現，這使我們能夠集中我們的人才並將我們的現金跑道延長到 2025 年，這提供了充足的資源並支持我們在 EDIT-301 試驗和推進中的持續進展我們在血紅蛋白病和其他體內發現方面的研究工作。有了這個，我會把電話交還給吉爾摩。

Thank you, Michelle. It has been almost 1 year since I joined Editas. In this time, the company has demonstrated 2 clinical proof of concepts, including a proof of concept for EDIT-301, which has the potential to be a competitive and differentiated product for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. In addition, as I stated in my opening remarks, we've taken a number of tangible steps to reshape the company around our new strategy, which we shared in early January and have begun executing on that strategy. And this is just the beginning.

謝謝你，米歇爾。加入 Editas 已經快一年了。此次，公司展示了2個臨床概念驗證，包括EDIT-301的概念驗證，它有潛力成為治療鐮狀細胞病和輸血依賴性β地中海貧血的具有競爭力的差異化產品。此外，正如我在開場白中所說，我們已經採取了一些切實的步驟來圍繞我們在 1 月初分享並開始執行該戰略的新戰略重塑公司。而這僅僅是個開始。

We look forward to continuing our transformation on sharing our progress with you. As a reminder, our strategic objectives for the year include providing clinical updates from the EDIT-301 RUBY study in June and end of 2023, providing clinical data from EDIT-301 EDITHAL trial for TDT by the end of 2023, dosing 20 total patients in our EDIT-301 RUBY study by year-end, hiring a new CSO with specific expertise aligned to our vision, advancing discovery of in vivo editing of hematopoietic stem cells and other tissues, and, finally, leveraging our robust IP portfolio and business development activities to drive value and complement our gene editing technology capabilities. I thank all the patients, investigators and our employees who are helping to drive our strategy forward. Thank you very much for your interest in Editas, and we're happy to answer questions. Thank you.

我們期待繼續轉型，與您分享我們的進步。提醒一下，我們今年的戰略目標包括在 6 月和 2023 年底提供 EDIT-301 RUBY 研究的臨床更新，在 2023 年底之前提供 EDIT-301 EDITHAL TDT 試驗的臨床數據，對 20 名患者進行給藥我們在年底前開展 EDIT-301 RUBY 研究，聘請具有符合我們願景的特定專業知識的新 CSO，推進造血幹細胞和其他組織體內編輯的發現，最後，利用我們強大的知識產權組合和業務發展活動推動價值並補充我們的基因編輯技術能力。我感謝所有幫助推動我們戰略向前發展的患者、研究人員和我們的員工。非常感謝您對 Editas 的關注，我們很樂意回答問題。謝謝。

(Operator Instructions) And our first question comes from Joon Lee with Truist Securities.

（操作員說明）我們的第一個問題來自 Truist Securities 的 Joon Lee。

Novartis recently terminated their sickle cell disease program after treating a couple of patients who observed no benefits. Given your editing strategy, it's similar to what Novartis says. Can you point to some differences why your promoter editing strategies should continue to work when Novartis failed? And I have a follow-up.

諾華公司最近在治療了幾名沒有發現任何好處的患者後終止了他們的鐮狀細胞病項目。鑑於你的編輯策略，它類似於諾華公司所說的。你能指出一些不同之處，為什麼你的啟動子編輯策略在諾華失敗後仍然有效嗎？我有一個後續行動。

Thanks very much, Joe. Yes, we did actually see that event some weeks or months ago. I think there are some elements that are critical. I think the first thing to point out that it -- is that in our initial POC readout at the end of last year, we actually saw a very robust data with increase in total hemoglobin, early increase in total hemoglobin as well as a robust fetal hemoglobin expression completely consistent with the preclinical data that were generated in testing our preclinical and our clinical hypotheses that our unique approach of combining an AsCas12a effector CRISPR enzyme with the targeting of a different region of the HBG-1, 2 promoter, which was much closer, in fact, actually encompasses the area in which we see deletions or mutations associated with hereditary persistence of fetal hemoglobin. I think we believe that all those factors point towards a key difference and differentiation, and indeed, our preclinical data and our clinical data have actually supported that hypothesis.

非常感謝，喬。是的，幾週或幾個月前我們確實看到了那個事件。我認為有些要素很關鍵。我想首先要指出的是，在我們去年年底的初步 POC 讀數中，我們實際上看到了一個非常可靠的數據，其中總血紅蛋白增加，總血紅蛋白早期增加以及強大的胎兒血紅蛋白表達與在測試我們的臨床前和臨床假設時產生的臨床前數據完全一致，即我們將 AsCas12a 效應子 CRISPR 酶與靶向 HBG-1、2 啟動子不同區域的獨特方法相結合，這更接近, 事實上，實際上涵蓋了我們看到與胎兒血紅蛋白遺傳持久性相關的缺失或突變的區域。我認為我們相信所有這些因素都指向一個關鍵的差異和差異，事實上，我們的臨床前數據和臨床數據實際上支持了這一假設。

Great. So can you remind me if you have any data preclinical? Having -- comparing the editing with the same region in Cas9 versus AsCas12 that you're using, and what the differences in outcome may be?

偉大的。如果你有任何臨床前數據，你能提醒我嗎？有——比較在 Cas9 中與您正在使用的 AsCas12 中相同區域的編輯，結果可能有什麼差異？

Sorry...

對不起...

Yes. So I mean, comparing Cas9, which is what I think Novartis use and AsCas12a, which is what you're using, you get a different outcomes if you were to target the same region in terms of getting deletions or (inaudible) ?

是的。所以我的意思是，比較我認為諾華公司使用的 Cas9 和你正在使用的 AsCas12a，如果你針對同一區域進行刪除或（聽不清），你會得到不同的結果？

Joon, I think you have a little bit breakdown, but let me try -- this is Baisong. Let me try and see whether I understand correctly. Echoing noise. So I think your question is to say compared to Novartis and do we have a comparison between Cas9 and AsCas12a and also the region just Gilmore mentioned. Is that your question?

Joon，我覺得你有點崩潰了，但讓我試試——我是 Baisong。讓我試試看我是否理解正確。迴聲。所以我認為你的問題是與諾華相比，我們是否對 Cas9 和 AsCas12a 以及 Gilmore 提到的區域進行了比較。那是你的問題嗎？

Yes. No, actually, if you target the same region either with Cas9 or Cas12a, what differences in outcome you get?

是的。不，實際上，如果你用 Cas9 或 Cas12a 靶向同一個區域，你會得到什麼不同的結果？

Yes. Let me just kind of in -- we did the comparison. We did -- from a clinical perspective, we scanned a large region of the promoter region to identify which areas to do the editing. So without too many specifics, but we covered a large region of the promoter in the HBG-1 and 2. And we find out that [mainly through] the region we selected, which Gilmore just mentioned, is consistent to the clinical observation for these HPFH. And then we also compared the Cas9 with Cas12 and we found the difference between Cas9 and Cas12. Does that answer your question?

是的。讓我來談談——我們做了比較。我們做到了——從臨床角度來看，我們掃描了啟動子區域的一大片區域，以確定要對哪些區域進行編輯。所以沒有太多細節，但我們覆蓋了 HBG-1 和 2 中啟動子的大部分區域。我們發現 [主要通過] 我們選擇的區域，Gilmore 剛才提到的，與這些的臨床觀察一致高爐然後我們還比較了 Cas9 和 Cas12，我們發現了 Cas9 和 Cas12 之間的區別。這是否回答你的問題？

Yes. No, absolutely. Your empiric data is so good, but just -- was just curious what was driving that difference.

是的。不，絕對。您的經驗數據非常好，但只是 - 只是好奇是什麼導致了這種差異。

Our next question is from Samantha Semenkow with Citi.

我們的下一個問題來自花旗銀行的 Samantha Semenkow。

Just a couple for me. For the presentation at EHA, will that -- is that a late-breaking presentation? I just wanted to clarify.

對我來說只是一對。對於 EHA 的演示，那會是一個最新的演示嗎？我只是想澄清一下。

Thanks, Samantha. I'll just have Baisong update, he'll give you detail there.

謝謝，薩曼莎。我會讓 Baisong 更新，他會在那裡給你詳細信息。

It is a normal oral presentation that is being accepted.

這是被接受的正常口頭陳述。

Okay. Got it. And then I also wanted to clarify, I heard you mention -- obviously, we'll have updated data for the first and second patients. And then I heard you, I think, say, 4 patients. So will it be 6 patients total that will get data on VOE? Or is that (inaudible) -- or is it 4 patients total?

好的。知道了。然後我還想澄清一下，我聽到你提到過——顯然，我們將更新第一名和第二名患者的數據。然後我聽到你說，我想，有 4 個病人。那麼總共有 6 名患者將獲得 VOE 數據嗎？或者是（聽不清）——還是總共有 4 名患者？

Total will be 4 patients at the EHA presentation.

在 EHA 演示中總共將有 4 名患者。

Got it. Okay. And then when you're making that cutoff for those incremental additional 2 patients, what level of follow-up was the cut off there. So I'm just curious, is it a couple of months? Or is it 1 month? Any information you can provide would be helpful.

知道了。好的。然後，當您為那些增加的額外 2 名患者設定截止值時，截止的後續級別是多少。所以我很好奇，是幾個月嗎？還是1個月？您可以提供的任何信息都會有所幫助。

Yes. We are -- for this next 2 patients, we have 2 months or more.

是的。我們 - 對於接下來的 2 名患者，我們有 2 個月或更長時間。

Just in follow-up, 1 other thing, I think it's important to understand that, obviously, we will -- because the abstract, which will be published later was based on data cut earlier, we will actually be presenting more data than in the abstract at the EHA Congress.

在後續行動中，另外一件事，我認為重要的是要理解這一點，顯然，我們會——因為稍後將發布的摘要是基於之前的數據剪切，我們實際上將呈現比之前更多的數據EHA 大會摘要。

Yes. Thanks, Gilmore. And just kind of also follow-up on that, the asset will be available on May 11.

是的。謝謝，吉爾摩。作為後續行動，該資產將於 5 月 11 日上市。

Next question is from Dae Gon Ha with Stifel.

下一個問題來自 Dae Gon Ha 和 Stifel。

Great. Look forward to the data update next month. So I guess I was just kind of wondering about your strategy going forward. So maybe if you can kind of walk us through how you're thinking about next programs or priorities beyond EDIT-301? I think Gilmore, you mentioned in vivo HSC editing. But curious, is delivery tech were less burdensome conditioning a stronger emphasis in your lineup? Or is it advancing new programs?

偉大的。期待下個月的數據更新。所以我想我只是想知道你未來的戰略。那麼，也許您可以向我們介紹一下您是如何考慮 EDIT-301 之後的下一個項目或優先事項的？我想 Gilmore，你提到了體內 HSC 編輯。但好奇的是，交付技術是否減輕了你的陣容的負擔？還是在推進新項目？

And if it's the latter, I guess, would you continue to do other ex vivo HSC, or is it more of an in vivo? And in that case, would you also think about other organs? Then I've got a follow-up.

如果是後者，我想，你會繼續做其他離體 HSC，還是更像是體內？那麼，您是否還會考慮其他器官？然後我有一個跟進。

Yes. Thanks very much, Dae Gon. We are -- the large part of our discovery focus is actually on in vivo. I think that was a very important part and pivot of our strategy because we believe that it maximizes the -- or maximizes our ability to exploit the powerful technology that we have available to us. From the point of HSCs, if you reduce the problem of in vivo to sort of 3 elements, selecting a robust effector molecule or enzyme, CRISPR enzyme, selecting a good target and then delivery, we believe that we have solved 2 of those problems, with very robust human data in the use of our Cas12a, CRISPR enzyme and the target of that specific HBG-1, 2 promoter. And so that reduces it to an in vivo delivery problem. As I said in my earlier remarks, our discovery group is actually working on that, and we look forward to updating more at an appropriate time in the future.

是的。非常感謝，大坤。我們是 - 我們發現重點的很大一部分實際上是在體內。我認為這是我們戰略的一個非常重要的部分和支點，因為我們相信它最大限度地——或最大化我們利用我們可用的強大技術的能力。從 HSC 的角度來看，如果你將體內問題簡化為 3 個要素，選擇一個強大的效應分子或酶，CRISPR 酶，選擇一個好的靶點然後遞送，我們相信我們已經解決了其中兩個問題，在使用我們的 Cas12a、CRISPR 酶和特定 HBG-1、2 啟動子的靶標方面擁有非常可靠的人類數據。因此，這將其簡化為體內遞送問題。正如我在之前的發言中所說，我們的發現小組實際上正在為此努力，我們期待在未來的適當時間更新更多內容。

I will say that we are looking actually also beyond HSCs to other tissues. And again, we'll give further updates in the future.

我要說的是，我們實際上也在尋找 HSC 以外的其他組織。再一次，我們將在未來提供進一步的更新。

Got it. And then second question, I just wanted to follow up on Baisong's commentary during prepared remarks. So as you were going into the field and kind of gauging physicians take on EDIT-301, you expressed or you commented on their high enthusiasm, wondering if you could comment, I guess, what proportion of those docs you visited are also looking to administer CTX001? And I guess, has there been any kind of gauge or ascertainment from your part as to what their sort of motivation would be in taking CTX001? Like are they lining up patients right now for CTX001? What kind of sentiment do you have? Are there any reservations on that approach? Any thoughts on that would be helpful.

知道了。然後是第二個問題，我只是想在準備好的發言中跟進白鬆的評論。因此，當您進入該領域並衡量醫生接受 EDIT-301 時，您表達或評論了他們的高度熱情，想知道您是否可以發表評論，我猜，您訪問過的那些文檔中有多少也希望管理CTX001？我想，您是否有任何衡量或確定他們服用 CTX001 的動機是什麼？就像他們現在正在為 CTX001 排隊嗎？你有什麼樣的情懷？對這種做法有任何保留意見嗎？對此的任何想法都會有所幫助。

Thanks for the question. Yes, I visited quite a few number of study sites. Actually, many of them are being participating in the previous gene editing trials. So they are very enthusiastic about the approach we are taking, including the different targeting region for editing and the different enzymes to do. And so actually, the benefit for us is those investigators have a lot of experience in this field.

謝謝你的問題。是的，我訪問了很多學習網站。實際上，他們中的許多人正在參與之前的基因編輯試驗。所以他們對我們正在採取的方法非常熱情，包括用於編輯的不同目標區域和不同的酶。所以實際上，對我們來說好處是那些調查人員在這個領域有很多經驗。

Yes. I think just building on Baisong's remarks, as you're obviously looking out towards the evolution of the market against the background of enthusiasm for our investigators and indeed the patients with the increase in our acceleration enrollment, we anticipate that in the future that the vast majority of patients will be awaiting dosing at the time of our launch. And I can go into more details on that. But I think, a very important point, I think something that has really resonated with the investigators is that our initial clinical data were very encouraging as presented in December, consistent with our preclinical data, and we're actually very confident that we will see replication in subsequent patients as we continue to monitor them through the execution of the 301 studies.

是的。我認為，基於 Baisong 的言論，您顯然是在對我們的研究人員以及我們加速註冊人數增加的患者充滿熱情的背景下展望市場的演變，我們預計未來會有大量在我們推出時，大多數患者將等待給藥。我可以詳細介紹一下。但我認為，非常重要的一點，我認為真正引起研究人員共鳴的是，我們在 12 月份提交的初始臨床數據非常令人鼓舞，與我們的臨床前數據一致，我們實際上非常有信心我們會看到隨著我們通過 301 研究的執行繼續監測他們，在隨後的患者中復制。

Our next question comes from Steven Seedhouse with Raymond James.

我們的下一個問題來自 Steven Seedhouse 和 Raymond James。

My question actually requires a bit of a prelude, so hopefully everyone can bear it for a moment. You made a comment on Globin Locus editing increasing fetal hemoglobin independent of erythropoietic stress. And as you know, the -- recent [ICER] report on exa-cel uncovered an ongoing phlebotomy, at least one in sickle cell and some of the earlier data releases for that program in thalassemia indicated phlebotomy use there as well, but that just stopped being reported at some moment.

我的問題其實有點前奏，希望大家忍一忍。您對 Globin Locus 編輯獨立於紅細胞生成應激的胎兒血紅蛋白增加發表了評論。正如你所知，最近關於 exa-cel 的 [ICER] 報告揭示了一項正在進行的放血手術，至少在鐮狀細胞中進行了一次放血，並且該計劃在地中海貧血中的一些早期數據發布表明那裡也使用了放血手術，但這只是在某個時刻停止被報告。

So it's not clear how prevalent phlebotomy use is for exa-cel. And this is all important because there was data at ASH years ago, as I'm sure you also know, indicating BCL11A editing cooperates with phlebotomy and primates to accentuate F cells and ultimately HBF levels probably because of the stress erythropoiesis it causes. So all that said, I'm curious if you agree that phlebotomy is potentially confounding fetal hemoglobin data for BCL11A approaches. And if you know what is the impact specifically where your editing approach at the HBG-1, 2 locus. What has phlebotomy use been like in your study and if you think this is all potentially a competitive advantage for you?

因此，尚不清楚 exa-cel 採血的普遍程度。這一點都很重要，因為多年前 ASH 就有數據，我相信你也知道，表明 BCL11A 編輯與放血和靈長類動物合作，以加強 F 細胞和最終的 HBF 水平，這可能是因為它引起的應激性紅細胞生成。綜上所述，我很好奇您是否同意放血可能會混淆 BCL11A 方法的胎兒血紅蛋白數據。如果您知道您在 HBG-1、2 位點的編輯方法的具體影響是什麼。在您的研究中採血的使用情況如何？您是否認為這對您來說都是潛在的競爭優勢？

Steve, thank you very much for your question. So from our own clinical data, preclinical data and also published clinical data, you're probably referring to for the BCL11A targeting approach. It did require some stimulation for the erythropoietic stress to increase the fetal hemoglobin -- sufficient fetal hemoglobin expression. And so that's actually the reason we're choosing the target that we are treating now, and we actually did take longer time to get all the targets from a preclinical study perspective, and that's been validated by other publications.

史蒂夫，非常感謝你的提問。因此，根據我們自己的臨床數據、臨床前數據以及已發布的臨床數據，您可能指的是 BCL11A 靶向方法。它確實需要對紅細胞生成應激進行一些刺激以增加胎兒血紅蛋白——足夠的胎兒血紅蛋白表達。所以這實際上是我們選擇我們現在治療的目標的原因，我們實際上確實花了更長的時間從臨床前研究的角度獲得所有目標，並且已經被其他出版物驗證。

And regarding specific clinical data for the BCL11 approach, I have not seen formal publication. So I would be waiting for them to publish their data and so we have a better understanding. So I will not comment on their data unless it is published.

至於 BCL11 方法的具體臨床數據，我還沒有看到正式發表。所以我會等待他們發布他們的數據，以便我們有更好的理解。因此，除非已發布，否則我不會評論他們的數據。

However, it is worth pointing out that in our early disclosure, we actually noticed the combination of a very robust normalization or correction of anemia in our first patients in December. And that was associated with a robust fetal hemoglobin expression, suggesting that indeed stress erythropoiesis, as we hypothesized, based on the known biology and our nonclinical data, that our approach is not dependent on stress erythropoiesis.

然而，值得指出的是，在我們早期的披露中，我們實際上註意到 12 月我們的第一批患者的貧血非常強大的正常化或糾正的組合。這與強大的胎兒血紅蛋白表達有關，這表明確實是應激性紅細胞生成，正如我們根據已知生物學和我們的非臨床數據假設的那樣，我們的方法不依賴於應激性紅細胞生成。

Thank you. Our next question is from Yanan Zhu with Wells Fargo.

謝謝。我們的下一個問題來自富國銀行的 Yanan Zhu。

Maybe to continue the discussion a little bit from the prior question, Gilmore, you mentioned that the total hemoglobin for the first patient is quite robust in the normal range. The percent of fetal hemoglobin appears to be very much in line with competitor gene editing product. So I was wondering, is the greater total hemoglobin reported for that patient, is that due to the total number of red blood cells? Is that -- could that potentially be a reason? Or could it be related to the baseline level of hemoglobin in that patient?

也許從前面的問題繼續討論一點，Gilmore，你提到第一位患者的總血紅蛋白在正常範圍內非常穩定。胎兒血紅蛋白的百分比似乎與競爭對手的基因編輯產品非常一致。所以我想知道，該患者報告的總血紅蛋白較高，是因為紅細胞總數嗎？那是——這可能是一個原因嗎？或者它可能與該患者的血紅蛋白基線水平有關嗎？

And along that line, to continue a little further and to perhaps looking into what we could expect from patient #2 at EHA, I was just wondering, could you remind us the baseline, total baseline hemoglobin for patient #2 and what is the normal range for the female patient, which obviously is the second patient?

沿著這條線，繼續深入研究我們對 EHA 患者 #2 的期望，我只是想知道，你能否提醒我們基線，患者 #2 的總基線血紅蛋白以及正常值是多少女性患者的範圍，這顯然是第二個患者？

So thanks for the question. And then on -- so I will start with answer to your first part of the question regarding the fetal hemoglobin versus the number of red blood cells and all of these. So what we see is actually robust erythropoiesis for these patients we observed. So their hemoglobin level is contributed by both the hemoglobin per cell as well as the number of red blood cells. And you can see that we actually do see the increase also on both end of that. And then also I want to mention that even though we also have like around 45% of fetal hemoglobin, and because of the total hemoglobin level is high and the total amount of fetal hemoglobin is also high. So that's kind of on that.

所以謝謝你的問題。然後 - 所以我將從回答你關於胎兒血紅蛋白與紅細胞數量和所有這些問題的第一部分開始。所以我們看到的實際上是我們觀察到的這些患者的強紅細胞生成。因此，他們的血紅蛋白水平是由每個細胞的血紅蛋白和紅細胞數量共同決定的。你可以看到，我們實際上確實看到了兩端的增長。然後我還想提一下，儘管我們也有大約 45% 的胎兒血紅蛋白，而且由於總血紅蛋白水平很高，胎兒血紅蛋白的總量也很高。所以就是這樣。

And then regarding the second patient, and we will present the data very soon. So I will not comment on the specifics of the patient data, but I can mention that, of course, the male and female normal hemoglobin level are different. Usually, for (inaudible) is around 13.5 to up to 18-gram per deciliter, for female is around 12 to 14, depending on the reference lab. So there's some difference in there, too.

然後關於第二位患者，我們將很快提供數據。所以我不會評論患者數據的細節，但我可以提一下，當然，男性和女性的正常血紅蛋白水平是不同的。通常，（聽不清）約為每分升 13.5 至 18 克，女性約為 12 至 14 克，具體取決於參考實驗室。所以那裡也有一些區別。

Okay. I think one other thing, you asked a question about what was the baseline hemoglobin of the Patient #1. And I think what we can say is that the hemoglobin or the total hemoglobin increase that we saw occur very rapidly, just within the first few months of dosing which comprised a 3.5 gram per deciliter increase.

好的。我想還有一件事，你問了一個關於 1 號患者的基線血紅蛋白是多少的問題。我想我們可以說的是，我們看到的血紅蛋白或總血紅蛋白增加非常迅速，就在給藥的前幾個月內，每分升增加 3.5 克。

Yes. Maybe just to add a little bit nuance on that baseline for sickle cell patients, [especially] for gene-editing trial. And because the patient when they prepare for apheresis and conditioning, they usually have blood transfusion. So the baseline actually we have is not the lowest level we recorded. We just set up the time of the visit 2 as a baseline.

是的。也許只是為了在鐮狀細胞患者的基線上添加一點細微差別，[特別是]基因編輯試驗。而且因為患者在準備單采和調理時，通常會進行輸血。所以我們實際擁有的基線並不是我們記錄的最低水平。我們只是將訪問 2 的時間設置為基線。

So actually it's compounded, it could be many different reasons for the baseline on that, too. That's just a nuance. It's actually -- it's lower than -- it's around the -- a little bit over 10 grams per deciliter when we actually on our record for this patient. This is just an example about the baseline, may be a little bit confusing.

所以實際上它是複雜的，也可能有許多不同的原因導致基線。這只是一個細微差別。實際上 - 它低於 - 它大約 - 當我們實際為該患者記錄時，每分升略高於 10 克。這只是一個關於基線的例子，可能有點令人困惑。

Very nice. Maybe a quick follow-up. Do you expect this to be also a differentiator for TDT and perhaps maybe at a greater level of significance because anemia is a major manifestation of that disease?

很不錯。也許快速跟進。您是否認為這也是 TDT 的一個區別因素，並且可能具有更大的意義，因為貧血是該疾病的主要表現？

Thanks very much, Yanan. We designed -- our discovery group and scientists designed and selected the combination of Cas12a with the specific targeting of the HBG-1, 2 promoter using a set of empirical experiments to determine what was the best approach to driving, not just fetal hemoglobin expression, but robust erythroid output that would be our red cell output for the bone marrow that would be independent of stress erythropoiesis or anemia. And those empirical experiments really determined that approaching or directly targeting the HBG-1, 2 promoter would be better. And that was the original design hypothesis.

非常感謝，延安。我們設計 - 我們的發現小組和科學家設計並選擇了 Cas12a 與 HBG-1、2 啟動子的特定目標的組合，使用一組經驗實驗來確定什麼是最好的駕駛方法，而不僅僅是胎兒血紅蛋白表達，但強大的紅細胞輸出將是我們的骨髓紅細胞輸出，它與應激性紅細胞生成或貧血無關。而那些實證實驗確實確定了接近或直接靶向 HBG-1、2 啟動子會更好。這就是最初的設計假設。

The nonclinical data, preclinical data actually supported that, showing robust erythroid output in comparison to other approaches as well as robust fetal hemoglobin expression. And indeed, that is what we have seen as we disclosed in our first sharing of the data or cut of the data from our RUBY study. And so, obviously, it is -- we haven't seen enough data in our EDITHAL patient. But what I can say is that RUBY has certainly demonstrated data that are consistent with both the preclinical data, which were supportive of the original biological and therapeutic hypotheses.

非臨床數據、臨床前數據實際上支持這一點，與其他方法相比顯示出強勁的紅細胞輸出以及強勁的胎兒血紅蛋白表達。事實上，這就是我們在第一次共享數據或從我們的 RUBY 研究中截取數據時所披露的情況。因此，很明顯，我們還沒有在 EDITHAL 患者身上看到足夠的數據。但我可以說的是，RUBY 確實展示了與臨床前數據一致的數據，這些數據支持最初的生物學和治療假設。

Our next question is from Philip Nadeau with TD Cowen.

我們的下一個問題來自 Philip Nadeau 和 TD Cowen。

This is [Armine Rodriguez] for Phils. On the sickle cell program, have you met with the FDA to gain better visibility on the regulatory path? And then a second question on the TDT program. For the year-end update, would that include only the sentinel patients that you initially dosed? Or will that -- will you disclose additional patients?

這是菲爾斯的 [Armine Rodriguez]。關於鐮狀細胞計劃，您是否與 FDA 會面以更好地了解監管路徑？然後是關於 TDT 計劃的第二個問題。對於年終更新，是否僅包括您最初給藥的哨兵患者？或者，你會透露更多的病人嗎？

And if you will be disclose any additional patients, are you planning on reporting when you switch from sentinel dosing to parallel dosing?

如果您要披露任何其他患者，您是否計劃在從前哨給藥切換到平行給藥時進行報告？

So I think what I do is ask Baisong. I've actually -- I'll keep track of the questions Baisong. If I'd ask you just to share the question on the FDA and the regulatory interactions .

所以我想我要做的就是問白松。實際上，我會跟踪 Baisong 的問題。如果我想請您分享有關 FDA 和監管互動的問題。

Yes. thanks for your question. So we certainly have a lot of engagement with FDA as you see that. Recently, we have the orphan drug designation. And from the registration perspective, we previously announced that we actually have the alignment on the potency assay with the FDA, which will -- FDA will consider with efficacy that data can be supporting registration. And we will have further engagement with the agency to align on the total registration package for the BLA submission, which is also planned.

是的。謝謝你的問題。因此，正如您所見，我們當然與 FDA 有很多合作。最近，我們獲得了孤兒藥稱號。從註冊的角度來看，我們之前宣布我們實際上與 FDA 在效力測定方面保持一致，這將 - FDA 將考慮數據可以支持註冊的有效性。我們將與該機構進一步接觸，以調整 BLA 提交的總註冊包，這也在計劃中。

And your second part of the question is about the beta thal data. So we are moving really along with the EDITHAL study, and we expect that we will have data by year-end, more than sentinel patient. And so we're looking forward to share that data by the year-end.

你的問題的第二部分是關於 beta thal 數據。因此，我們正在真正與 EDITHAL 研究一起前進，我們預計到年底我們將獲得數據，而不是哨兵患者。因此，我們期待在年底前分享這些數據。

All right. I see. And you are more than sentinel patient. So are you planning to disclose when you are going to have proof to continue parallel dosing before then?

好的。我懂了。而且你不僅僅是哨兵病人。那麼，您是否計劃在此之前披露您何時能獲得繼續平行給藥的證據？

Okay. So what we are actually planning to do is -- I think the key thing is we're on track to get the data for readout at the end of the year for that initial readout at the end of the year. We haven't determined if we're actually going to share that. But I think the important point is that we are well on track to disclose good initial data for the end of the year.

好的。所以我們實際上計劃做的是——我認為關鍵是我們正在按計劃在年底獲取數據以進行初始讀數。我們還不確定我們是否真的要分享它。但我認為重要的一點是我們有望在年底披露良好的初步數據。

Our next question comes from Rick Bienkowski with Cantor Fitzgerald.

我們的下一個問題來自 Rick Bienkowski 和 Cantor Fitzgerald。

And congrats on all the progress. I guess I'll expand a bit on the last question on the path towards registration for EDIT-301. 20 patients is a pretty substantial cohort size in sickle cell disease. So do you have any sense of how many patients' worth of data you will need for a registrational filing?

並祝賀所有的進步。我想我會在關於 EDIT-301 註冊路徑的最後一個問題上做一些擴展。 20 名患者是鐮狀細胞病的相當大的隊列規模。那麼，您是否知道註冊申請需要多少患者數據？

Thank you for the question. So we certainly think that with the gene editing approach that we have -- we will be able to generate a substantial amount of data. And the specifics on the number of patients to be able to use for registration, we need to align with the regulatory agencies. So we are planning to discuss with FDA.

感謝你的提問。所以我們當然認為，通過我們擁有的基因編輯方法——我們將能夠生成大量數據。以及能夠用於註冊的患者數量的具體細節，我們需要與監管機構保持一致。所以我們計劃與 FDA 進行討論。

Okay. Got it. And I just have another quick one. I was hoping for a little bit more granularity on the collaborative revenues for the quarter. Were all of the $9.9 million in revenue attributable to the Shoreline transaction? Or are there some other revenues attributable to other partnerships in there?

好的。知道了。我還有另一個快速的。我希望本季度的協作收入更加精細。 990 萬美元的收入是否全部歸因於 Shoreline 交易？還是那裡有一些其他收入歸因於其他合作夥伴關係？

It's a combination of both the Shoreline and then some other small sublicense revenues.

它是海岸線和其他一些小的從屬許可收入的結合。

Our next question is from Rich Law with Credit Suisse.

我們的下一個問題來自瑞士信貸的 Rich Law。

I have a couple of questions for you guys. So with the appeal litigation pending, what does it mean for companies such as CRISPR and Vertex that already filed a BLA for exa-cell that utilize CRISPR/Cas9 from your IP perspective. They don't have a license from you or the brow and could potentially launch the product before we know the outcome of the appeal. So any insight here would be helpful. And then I have a follow-up question.

我有幾個問題要問你們。因此，隨著上訴訴訟懸而未決，這對於 CRISPR 和福泰（Vertex）等已經為使用 CRISPR/Cas9 的 exa-cell 提交 BLA 的公司從您的知識產權角度來看意味著什麼。他們沒有您或眉毛的許可，並且可能會在我們知道上訴結果之前推出該產品。所以這裡的任何見解都會有所幫助。然後我有一個後續問題。

Okay. Thanks very much, Rich. I think the key thing is that we sort of anticipate the judgment in the early to mid-2024. We are confident that we will prevail as we have before, largely because what are under discussion is the application of the law and not about new facts, and it's the application of a -- by PTAB. Now setting aside that interference, I think the important thing is to say that we have a portfolio of IP not subject to any interference that actually covers product in development using Cas9 for the application of human therapeutics. And, looking forward, we are happy to grant licenses to enable delivery of this technology to patients, and believe that we should recognize significant value around that.

好的。非常感謝，里奇。我認為關鍵是我們可以預見到 2024 年初至中期的判斷。我們相信我們會像以前一樣獲勝，主要是因為正在討論的是法律的應用，而不是關於新事實，這是 PTAB 的應用。現在拋開這種干擾，我認為重要的是說我們擁有不受任何干擾的 IP 組合，實際上涵蓋了使用 Cas9 進行人類治療應用的開發產品。並且，展望未來，我們很高興授予許可，使這項技術能夠交付給患者，並相信我們應該認識到它的重要價值。

Okay. Great. So in terms of [branding] license, so we're not going to know the appeal decision likely before the BLA and also potentially the launch? Like how do you sort of think about that?

好的。偉大的。因此，就 [品牌] 許可而言，我們不會知道可能在 BLA 之前做出的上訴決定，也可能不知道發布的決定？比如你是怎麼想的？

Well, I think there are a number of important points to make. I think the first, again, is just to remind that the appeal applies to some of our Cas9 in-human therapeutics IP estate, but not all. I think it's important to emphasize that we have Cas9, or IP around Cas9 use in human therapeutics that is not subject to any interference, and therefore, is not subject to that appeal case. And we actually believe that it actually covers product in development. And so what I think I want people to really understand is that, that appeals case is around interference on some of our IP estate, but not all.

好吧，我認為有許多要點需要說明。我認為，首先，再次提醒，上訴適用於我們的一些 Cas9 人體治療 IP 財產，但不是全部。我認為重要的是要強調我們擁有 Cas9，或圍繞 Cas9 在人類治療中使用的 IP 不受任何干擾，因此不受上訴案件的約束。我們實際上相信它實際上涵蓋了開發中的產品。所以我想我想讓人們真正理解的是，那個上訴案是關於對我們的一些知識產權財產的干擾，但不是全部。

Okay. Got it. And then just one more question from me. So you're seeing some next-gen [SCD] therapy is already in development with new conditioning agents. So if they'll succeed, it doesn't seem like the shelf life for these first-gen therapies will last too long. Any thoughts about this?

好的。知道了。然後我再問一個問題。所以你看到一些下一代 [SCD] 療法已經在開發新的調理劑。因此，如果他們成功，這些第一代療法的保質期似乎不會持續太久。對此有什麼想法嗎？

So just to be clear, I understand your question. You're actually questioning if the evolution of new conditioning would actually change the landscape for the products that are either -- are close to approval? I think it really very much depends on the nature of the conditioning. As we look out at [toxification], obviously it's something we've looked at closely, one of the important things is to balance both the reduction of toxicities with engraftment efficacy. And I think we all see that it's a very important path to increasing eligibility for patients because more patients will be able to tolerate a nongenotoxic less toxic conditioning regime. Many of the regimes or some of the approaches are not actually editing dependent. They are actually -- and so what we actually believe is that the evolution of mild deconditioning could actually expand and grow the size of the eligible patient population for all.

所以要明確一點，我理解你的問題。你實際上是在質疑新調理的發展是否真的會改變那些接近批准的產品的前景？我認為這在很大程度上取決於條件反射的性質。當我們關注 [毒化] 時，顯然這是我們密切關注的事情，其中重要的事情之一是平衡降低毒性和植入效果。而且我認為我們都看到這是提高患者資格的一條非常重要的途徑，因為更多的患者將能夠耐受非遺傳毒性、毒性較小的調節方案。許多製度或一些方法實際上並不依賴於編輯。它們實際上是——所以我們真正相信的是，輕度去適應症的演變實際上可以擴大和增加所有人符合條件的患者群體的規模。

I think the important thing, obviously, also is that we are looking beyond, not just conditioning, but looking to in vivo editing as part of our strategy for the very simple reason that we believe that in vivo editing will further increase the eligibility of the patient population for treatment.

我認為重要的是，顯然，我們正在超越，不僅僅是調節，而是將體內編輯作為我們戰略的一部分，原因很簡單，我們相信體內編輯將進一步提高接受治療的患者群體。

Our next question is from Debjit Chattopadhyay with Guggenheim.

我們的下一個問題來自古根海姆的 Debjit Chattopadhyay。

This is Ray Forseth on for Debjit. I just want to build off for the conditioning discussion and sort of get an outline of your strategy. Is it sort of bifurcated kind of exploring both in vivo editing and the opportunity to in-license assets that would be alternative to busulfan. Can you sort of map that out for us? And just wanted to get your thoughts, too, on the ASGCT abstracts and sort of what you see in the competitive landscape around conditioning, especially given that a competitor is kind of moving forward with the CD117 approach?

我是 Debjit 的 Ray Forseth。我只是想為調節討論做準備，並大致了解您的策略。這是否是一種分叉的探索，既探索體內編輯，又探索可替代白消安的許可資產的機會。你能幫我們把它畫出來嗎？也只是想了解您對 ASGCT 摘要的看法，以及您在圍繞條件反射的競爭格局中看到的某種東西，特別是考慮到競爭對手正在推進 CD117 方法？

Thanks very much, Debjit. I think I'll start and then I will have Baisong comment. From a strategic point of view, we are using a two-pronged strategy. We have directed investment, significant investment internally to our discovery of in vivo editing for hematopoietic stem cells. And I think, as I said earlier, we believe that this is a problem that we can focus on -- where we can focus on delivery, where certainly in humans, we believe we have solved the -- 2 of the 3 challenges around the selection of a CRISPR enzyme as well as a target.

非常感謝，Debjit。我想我會開始，然後我將有白松評論。從戰略的角度來看，我們採用雙管齊下的策略。我們已經進行了直接投資，內部的重大投資是為了發現造血幹細胞的體內編輯。我認為，正如我之前所說，我們相信這是一個我們可以關注的問題——我們可以專注於交付，當然在人類身上，我們相信我們已經解決了——圍繞 3 個挑戰中的 2 個選擇 CRISPR 酶以及靶標。

In parallel, we actually are continuing -- have ongoing evaluations of milder conditioning approaches. And I think you asked more importantly, or in follow-up a question about the, for example, CD117, I'll ask Baisong just to talk about that.

與此同時，我們實際上正在繼續——對更溫和的調節方法進行持續評估。我認為你問的更重要，或者在後續問題中，例如 CD117，我會請白松來談談這個問題。

Thanks for your question. I can say that we have looked into this smart conditioning very deep, looking the space as well as internal efforts wise. And there were generally probably 2 approaches. One is that CD117 antibody and in that direction. And the other one is actually doing the same modification together with gene editing. So the latter approach is still -- is in the infancy, if I may say, and the previous approach with antibody have many different exercise on that.

謝謝你的問題。我可以說我們已經非常深入地研究了這種智能調節，從空間和內部努力來看都是明智的。通常可能有兩種方法。一個是 CD117 抗體和那個方向。而另一個實際上是在進行相同的修改和基因編輯。所以後一種方法仍然 - 處於起步階段，如果我可以說的話，而以前的抗體方法在這方面有很多不同的練習。

So I think we are very closely monitoring the space and understand these. And I also want to mention that the [model of] conditioning, if successful, is not going to be only successful for sickle cell transplant, it's going to be successful for leukemia and many different gene -- therapeutic areas. So we are actually very much looking into this space.

所以我認為我們正在非常密切地監視這個空間並了解這些。我還想提一下，如果條件反射 [model of] 成功，它不僅會在鐮狀細胞移植方面取得成功，還會在白血病和許多不同的基因治療領域取得成功。所以我們實際上非常關注這個領域。

Our next question is from Madhu Kumar with Goldman Sachs.

我們的下一個問題來自高盛的 Madhu Kumar。

This is Rob on for Madhu. We were just wondering how should we think about forward OpEx, particularly R&D given the robust recruitment into RUBY? And how long will spend be around cell editing and transplants versus follow-up?

這是馬杜的羅布。我們只是想知道我們應該如何考慮未來的運營支出，特別是考慮到 RUBY 的強勁招聘？圍繞細胞編輯和移植與隨訪將花費多長時間？

I'm sorry, Rob, I actually had great difficulty hearing your question. Could you just repeat it, please?

對不起，Rob，我實際上很難聽到你的問題。請你重複一遍好嗎？

Sure. We are just wondering how we should be thinking about forward OpEx, particularly spending in regard to transfusions versus follow-up?

當然。我們只是想知道我們應該如何考慮未來的運營支出，特別是輸血與後續方面的支出？

Okay. So I think you're asking -- if I'm clear, you're asking about forward-looking OpEx around the execution of the Ruby study. Is that correct? Okay. Michelle?

好的。所以我想你是在問——如果我清楚的話，你是在問圍繞 Ruby 研究執行的前瞻性 OpEx。那是對的嗎？好的。米歇爾？

Yes. So -- so Rob, I mean, we still disclose our annual OpEx or our quarterly OpEx, but I can tell you that about half of our spend is in -- on the both the RUBY trial and the TDT trial. So we don't expect an enormous increase quarter-over-quarter. And -- but as we do -- as we do dose more patients, obviously, our R&D spend will go up, but not substantially.

是的。所以 - 所以 Rob，我的意思是，我們仍然會披露我們的年度運營支出或季度運營支出，但我可以告訴你，我們大約一半的支出用於 RUBY 試驗和 TDT 試驗。因此，我們預計季度環比不會出現大幅增長。而且——但正如我們所做的那樣——當我們給更多的病人服用藥物時，顯然，我們的研發支出會增加，但不會大幅增加。

And our current -- I'll just say one more -- our current cash runway support our RUBY trials.

我們目前——我再說一個——我們目前的現金跑道支持我們的 RUBY 試驗。

Our next question is from Greg Harrison with Bank of America.

我們的下一個問題來自美國銀行的 Greg Harrison。

This is Mary Keith on for Greg. So with 19 patients enrolled and plans for 20 to be dosed by year-end, maybe how many sickle cell patients have been currently treated with EDIT-301 -- and maybe how could we expect to see this represented in the efficacy readout by the year-end update?

這是格雷格的瑪麗基思。因此，有 19 名患者入組併計劃在年底前對 20 名患者進行給藥，也許目前有多少鐮狀細胞患者接受了 EDIT-301 治療——也許我們怎麼能期望在今年的療效讀數中看到這一點-結束更新？

Thanks for the question, Mary. So we have 19 patients enrolled. And among those, as we just mentioned, 4 have been dosed, and we actually have more patients have been completed apheresis, have CD34 cells edited and ready to schedule dosing. And then we have other patients who are in the process of apheresis. And so we are very confident that we will be able to dose 20 patients by year-end.

謝謝你的問題，瑪麗。所以我們有 19 名患者入組。正如我們剛才提到的，其中有 4 人已經給藥，實際上我們有更多的患者已經完成了單採術，編輯了 CD34 細胞並準備好安排給藥。然後我們還有其他患者正在接受單採術。因此，我們非常有信心在年底前能夠為 20 名患者給藥。

Our next question is from Luca Issi with RBC Capital Markets.

我們的下一個問題來自 RBC Capital Markets 的 Luca Issi。

Great. Maybe on beta-thalassemia, obviously most patients are in Southern Europe, so wondering if you could comment on what's the plan to capture that market? And maybe how you're thinking about some of the key lessons learned from the unsuccessful launch of [LiverBio] there? And then maybe on sickle cell disease, wondering if you can comment on pricing. Obviously, active report suggest $1.9 million. So wondering if that is actually aligned with your thinking. And then maybe lastly on LCA10, any update on partner discussions there?

偉大的。也許就 β-地中海貧血而言，顯然大多數患者都在南歐，所以想知道您是否可以評論一下佔領該市場的計劃是什麼？也許你是如何思考從 [LiverBio] 的失敗推出中吸取的一些重要教訓的？然後可能是關於鐮狀細胞病，想知道你是否可以對定價發表評論。顯然，活躍報告建議 190 萬美元。所以想知道這是否真的符合你的想法。然後也許最後在 LCA10 上，關於合作夥伴討論的任何更新？

Thanks very much, Luca. So obviously, beta-thalassemia is a disease that dominates parts of the world, particularly Europe, Southeast Asia, South Asia, amongst others. From a point of view of our forward-looking, we are actually focusing our efforts on North America currently. We have shared in the past that from an upside point of view, we are looking -- open to partnering, ideally targeting a partner with a large global footprint who would actually collaborate certainly in sort of ex-U.S. development and commercialization. So that's what I would say I can talk about when we look to your point about beta-thalassemia outside North America.

非常感謝，盧卡。很明顯，β-地中海貧血是一種主宰世界部分地區的疾病，尤其是歐洲、東南亞、南亞等。從我們前瞻性的角度來看，我們目前實際上是在把精力放在北美。我們過去曾分享過，從好的方面來看，我們正在尋找——對合作持開放態度，理想情況下，目標是一個在全球範圍內具有廣泛影響力的合作夥伴，他們實際上肯定會在美國以外的地方進行合作。開發和商業化。所以這就是我想說的，當我們看到你關於北美以外的β-地中海貧血的觀點時，我可以談論。

I will say that we are happy, very happy with the progress that we're making with execution here within the United States and North America.

我要說的是，我們很高興，非常高興我們在美國和北美的執行方面取得的進展。

With regard to pricing, I think it's very early days yet for us to be talking about pricing. This is something that we would be very happy to discuss when we're actually closer to approval and launching, and we look forward to future conversations around there. Obviously, we look to the market evolution over that time, but we're going to talk about that closer to launch and approval.

關於定價，我認為我們現在談論定價還為時過早。當我們實際上接近批准和啟動時，我們會非常樂意討論這個問題，我們期待著未來的對話。顯然，我們著眼於那段時間的市場演變，但我們將在更接近發布和批准的時候討論這一點。

And then finally, with regard to LCA10, we have -- we really have a practice of not really going into details until we have a deal signed and executed.

最後，關於 LCA10，我們確實有一種做法，即在我們簽署並執行交易之前不會真正深入細節。

And maybe just to add 1 more point, sorry, just adding 1 more point, as Gilmore mentioned, our pricing, right? So certainly, we are very early stage, and we are happy to see the community is looking to the value of these gene editing therapy, and we are happy to see that the ICER report recently in this space. So we -- as Gilmore mentioned, this will be evolving, but we are pleased to see that the entire community recognizes the value of the medicine in this field.

也許只是再增加 1 分，抱歉，只是再增加 1 分，正如 Gilmore 提到的，我們的定價，對嗎？所以當然，我們還處於早期階段，我們很高興看到社區正在關注這些基因編輯療法的價值，我們很高興看到最近在這個領域的 ICER 報告。所以我們 - 正如 Gilmore 提到的那樣，這將不斷發展，但我們很高興看到整個社區都認識到醫學在這一領域的價值。

Our next question is from Jay Olson with Oppenheimer.

我們的下一個問題來自 Jay Olson 和 Oppenheimer。

This is Cheng Li on the line for Jay. Maybe 2 from us. So I'm just wondering if there's a chance where you have the capacity to dose more than 20 patients for the sickle cell disease program this year? And second question is on your ex-U.S. strategy. What you are trying to thinking? And if you are planning to partner that program, what is that timing to do that?

我是程莉，為傑伊接聽電話。也許我們有 2 個。所以我想知道今年你們是否有能力為 20 多名鐮狀細胞病患者提供藥物？第二個問題是關於你的前美國。戰略。你在想什麼？如果您打算與該計劃合作，那麼什麼時候可以這樣做？

Thanks very much. So do we have capacity to dose more than 20 patients? Yes. One of the important points, when we rolled out our strategy, was to, again, sharpen our focus on developing and accelerating 301. And indeed, we have deployed capital to enable, not just the acceleration on the clinical side, but actually also to ensure that we have capacity to edit or other CMC capacity to edit and support those -- that clinical acceleration. So indeed, we do have that capacity to dose more than 20 patients.

非常感謝。那麼我們是否有能力為超過 20 名患者給藥？是的。當我們推出我們的戰略時，重要的一點是再次加強我們對開發和加速 301 的關注。事實上，我們已經部署了資金來實現，不僅是臨床方面的加速，而且實際上也是確保我們有能力編輯或其他 CMC 能力來編輯和支持那些——臨床加速。所以事實上，我們確實有能力為 20 多名患者給藥。

And then I think your second question was around ex-U.S. and the timing of partnership. I think as I said before, we are -- we are interested in partnering. We're looking to a partner with a global footprint that would actually certainly support ex-U.S., particularly on the development and commercialization. And with regard to timing, we wouldn't really discuss the timing until we actually have a deal signed and executed.

然後我認為你的第二個問題是關於前美國的。以及合作的時機。我認為正如我之前所說，我們 - 我們有興趣合作。我們正在尋找一個足跡遍布全球的合作夥伴，該合作夥伴實際上肯定會支持美國以外的地區，特別是在開發和商業化方面。關於時間安排，在我們真正簽署並執行交易之前，我們不會真正討論時間安排。

Our next question is from Joel Beatty with Baird.

我們的下一個問題來自 Joel Beatty 和 Baird。

This is Vendrom Peluchon for Joel. Looking across other late-stage products in sickle cell and TDT, it appears that data sets of 30 patients could support approval. So with Editas being on track to dose 20 patients by year-end, how quickly do you think you'll be able to secure the necessary data to support regulatory approvals?

這是 Joel 的 Vendrom Peluchon。縱觀鐮狀細胞和 TDT 的其他後期產品，30 名患者的數據集似乎可以支持批准。因此，隨著 Editas 有望在年底前對 20 名患者進行給藥，您認為您能夠多快獲得必要的數據以支持監管批准？

Thanks very much, Ben. Baisong?

非常感謝，本。白松？

Thanks for the question. As I mentioned earlier, in terms of total number of patients required to support the registration and then need to have required alignment with the regulatory agency. And in terms of the progression of the study, we are very positive about the momentum. So we are very optimistic that we will be able to dose patients as we planned.

謝謝你的問題。正如我之前提到的，就支持註冊所需的患者總數而言，然後需要與監管機構保持一致。就研究的進展而言，我們對勢頭非常樂觀。因此，我們非常樂觀地認為，我們將能夠按照我們的計劃對患者進行給藥。

So I think the key thing, Ven, is that you've actually identified sort of a benchmark. But obviously, what we need to do is as planned that sit with the regulators and come to an agreement on what the data set they would like to see for our programs.

所以我認為關鍵是，Ven，你實際上已經確定了某種基準。但顯然，我們需要做的是按計劃與監管機構坐在一起，就他們希望我們的項目看到哪些數據集達成協議。

Our next question is from Joon Lee with Truist Securities.

我們的下一個問題來自 Truist Securities 的 Joon Lee。

And sorry for the background noise. So I had the same question -- I had the same question as Steve, but maybe a different way of asking what percentage of sickle cell patients with hereditary persistence of fetal hemoglobin have mutations along the globin locus versus the BCL11A locus?

抱歉背景噪音。所以我有同樣的問題——我和史蒂夫有同樣的問題，但也許是一種不同的方式來詢問遺傳性胎兒血紅蛋白持續存在的鐮狀細胞患者中有多少百分比沿珠蛋白基因座與 BCL11A 基因座發生突變？

Joon, thank you for your question. So we do not have all the specifics on your question on that, but what we know is the mutation -- the promoter region directly impact the fetal hemoglobin expression. But PCoA is a transcription factor, which impacts multiple different [shell] units. And the mutation of the BCL11A will have much different impact from the fetal hemoglobin and expression only will have other impacts, too. So the genetic mutation is a much more complicated issue than the HBF with the promoter region and mutation for the gamma-globulin promoters.

俊，謝謝你的問題。所以我們沒有關於你的問題的所有細節，但我們知道的是突變——啟動子區域直接影響胎兒血紅蛋白的表達。但 PCoA 是一種轉錄因子，它會影響多個不同的 [shell] 單元。而 BCL11A 的突變將產生與胎兒血紅蛋白和表達有很大不同的影響，也會產生其他影響。因此，基因突變是一個比具有啟動子區域和γ-球蛋白啟動子突變的HBF複雜得多的問題。

I think another way, Joon, to actually characterize this because some of the prevalence is a little harder to quantify. But another way of pointing it is really the strength of the signal, the hereditary persistence of fetal hemoglobin and its capacity to substantially mitigate the effect of sickle cell disease and thalassemia, were actually determined actually quite some time ago because this phenotypic change and the phenotype-to-genotype correlation was actually quite robust and identified actually a few decades ago, whereas the BCL11A was identified really through a GWAS assessment, genome-wide assessment.

Joon，我想用另一種方式來實際描述這一點，因為一些流行程度有點難以量化。但另一種指向它的方式實際上是信號的強度，胎兒血紅蛋白的遺傳持久性及其顯著減輕鐮狀細胞病和地中海貧血影響的能力，實際上在很久以前就已經確定了，因為這種表型變化和表型與基因型的相關性實際上非常穩健，實際上在幾十年前就已確定，而 BCL11A 確實是通過 GWAS 評估、全基因組評估確定的。

We have reached the end of the Q&A session. And with that, ladies and gentlemen, this concludes today's call. Thank you once again for your participation. You may now disconnect your lines.

問答環節已經結束。女士們先生們，今天的電話會議到此結束。再次感謝您的參與。您現在可以斷開線路。