Taysha Gene Therapies, Inc. (TSHA) 2026 Q1 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Taysha Gene Therapies first-quarter 2026 financial results conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

各位好，感謝您耐心等候。歡迎參加 Taysha Gene Therapies 2026 年第一季財務業績電話會議。（接線員指示）敬請注意，今日會議將被錄音。

I would now like to hand the conference over to your first speaker today, Hayleigh Collins, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

現在我想將會議交給今天的第一位講者，企業傳播與投資人關係資深總監 Hayleigh Collins。請開始。

Thank you. Good morning, and welcome to Taysha's first-quarter 2026 financial results and corporate update conference call. Earlier today, Taysha issued a press release announcing financial results for the quarter ended March 31, 2026. A copy of this press release is available on the company's website and through our SEC filings.

謝謝。各位早安，歡迎參加 Taysha 2026 年第一季財務業績與公司最新進展電話會議。今日稍早，Taysha 已發布新聞稿，公布截至 2026 年 3 月 31 日止季度的財務業績。該新聞稿可於公司網站及我們向美國證券交易委員會（SEC）提交的文件中取得。

Joining me on today's call are Sean Nolan, Taysha's Chief Executive Officer; Sukumar Nagendran, President and Head of R&D; and Kamran Alam, Chief Financial Officer. We will hold a question-and-answer session following our prepared remarks.

今天與我一同參與電話會議的有：Taysha 執行長 Sean Nolan；研發總裁暨研發主管 Sukumar Nagendran；以及財務長 Kamran Alam。在我們的事先準備發言結束後，將進行問答環節。

On today's call, we will be making forward-looking statements, including statements concerning the potential of TSHA-102, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials, including with respect to functional milestones to positively impact quality of life and alter the course of disease in the patients we seek to treat; our research, development and regulatory plans for our product candidates, including the timing of initiating additional trials, reporting data from our clinical trials, making regulatory submissions, timing our outcomes of communications with the FDA and the regulatory pathway for TSHA-102, the potential for the product candidate to receive regulatory approval from the FDA or equivalent foreign regulatory agencies; our ability to realize benefits of breakthrough therapy designations for TSHA-102; our ability to drive long-term value for stockholders; and the market opportunity for our programs.

在今天的電話會議中，我們將發表前瞻性陳述，包括關於 TSHA-102 潛力的陳述，其中包括：截至目前在臨床試驗中已給藥患者所初步觀察到之任何有利結果的可重現性與持久性；包括就功能性里程碑而言，是否能對生活品質產生正面影響並改變我們欲治療患者的疾病進程；我們對產品候選物的研究、開發與法規計畫，包括啟動額外試驗的時程、公布臨床試驗數據、提出法規申請、與 FDA 溝通結果的時程，以及 TSHA-102 的法規審查途徑；該產品候選物獲得 FDA 或同等海外主管機關核准的可能性；我們實現 TSHA-102 突破性療法認定效益的能力；我們為股東創造長期價值的能力；以及我們各項計畫的市場機會。

This call may also contain forward-looking statements relating to Taysha's growth, forecasted cash runway and future operating results, discovery and development of product candidates, strategic alliances, and intellectual property, as well as matters that are not historical facts or information. Various risks may cause Taysha's actual results to differ materially from those stated or implied in such forward-looking statements. For a list and description of the risks and uncertainties that we face, please see the reports that we have filed with the SEC, including in our annual report on Form 10-K for the full year ended December 31, 2025, that we filed on March 19, 2026, and our quarterly report on Form 10-Q for the quarter ended March 31, 2026, that we filed today.

本次電話會議亦可能包含與 Taysha 成長、預估現金可支撐期間（cash runway）及未來營運結果、產品候選物的發現與開發、策略聯盟與智慧財產權相關的前瞻性陳述，以及非歷史事實或資訊之事項。多項風險可能導致 Taysha 的實際結果與此等前瞻性陳述所明示或暗示者存在重大差異。關於我們所面臨之風險與不確定性的清單與說明，請參閱我們向 SEC 提交的報告，包括截至 2025 年 12 月 31 日止年度之 Form 10-K 年報（我們於 2026 年 3 月 19 日提交）以及截至 2026 年 3 月 31 日止季度之 Form 10-Q 季報（我們於今日提交）。

This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast, May 6, 2026. Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities laws.

本次電話會議包含具時效性之資訊，僅在本次直播日期（2026 年 5 月 6 日）當日為準確。除非適用證券法另有要求，Taysha 不承擔修訂或更新任何前瞻性陳述以反映本次電話會議日期之後事件或情況的義務。

With that, I would now like to turn the call over to our CEO, Sean Nolan.

接下來，我想將電話會議交給我們的執行長 Sean Nolan。

Thank you, Hayleigh, and welcome, everyone, to our first-quarter 2026 financial results and corporate update conference call.

謝謝你，Hayleigh，也歡迎各位參加我們 2026 年第一季財務業績與公司最新進展電話會議。

On today's call, I will begin with an update on our recent regulatory, clinical, and commercial readiness activities. Dr. Suku Nagendran, President and Head of R&D, will outline recently published preclinical data that continue to validate our novel TSHA-102 construct design and minimally invasive intrathecal route of administration. Kamran Alam, our Chief Financial Officer, will follow up with a financial update, and I will provide closing remarks and open the call for questions.

在今天的電話會議中，我將先就我們近期在法規、臨床與商業化準備方面的活動進行更新。研發總裁暨研發主管 Suku Nagendran 醫師將概述近期發表的臨床前數據，該等數據持續驗證我們新穎的 TSHA-102 構築體設計以及微創的鞘內給藥途徑。接著，我們的財務長 Kamran Alam 將提供財務更新；最後我將作結並開放提問。

We entered 2026 focused on a disciplined execution across our regulatory, clinical, and pre-commercialization activities for TSHA-102, with the goal of delivering a potentially transformative therapy to a broad population of patients with Rett syndrome who continue to face high unmet need. Over the past several months, we have continued to advance our TSHA-102 clinical development program and made progress towards key clinical milestones anticipated in the second quarter of 2026.

我們在進入 2026 年時，聚焦於以嚴謹且有紀律的方式推進 TSHA-102 的法規、臨床與商業化前準備活動，目標是為仍面臨高度未被滿足醫療需求的廣大雷特氏症患者族群，提供一項可能具變革性的療法。在過去數月中，我們持續推進 TSHA-102 的臨床開發計畫，並朝向預期於 2026 年第二季達成的關鍵臨床里程碑取得進展。

On the regulatory front, we recently held an initial breakthrough therapy Type B multidisciplinary meeting with the FDA. During the meeting, we reaffirmed alignment on the planned pathway toward a BLA submission for TSHA-102, covering the pivotal trial design, endpoints, and BLA submission scenarios, including the potential to submit for approval based on a six-month interim analysis from the REVEAL pivotal trial. We believe our consistent, constructive dialogue with the FDA continues to support our streamlined path toward a potentially expedited BLA submission.

在法規方面，我們近期與 FDA 舉行了首次突破性療法 Type B 多學科會議。會議期間，我們再次確認就 TSHA-102 之 BLA 申請提交的既定路徑達成一致，涵蓋關鍵性試驗設計、終點，以及 BLA 提交情境，包括可能基於 REVEAL 關鍵性試驗六個月期中分析而提出核准申請的可能性。我們相信，與 FDA 持續一致且具建設性的對話，將繼續支持我們朝向可能加速的 BLA 提交之精簡路徑。

Additionally, in the first quarter of 2026, we held a Type C meeting with the FDA, where the FDA endorsed our proposed Process Performance Qualification, or PPQ, campaign strategy, in support of our planned BLA submission. I am pleased to share that we initiated the BLA-enabling PPQ campaign using our TSHA-102 commercial manufacturing process in April, and we expect a complete execution by the fourth quarter of this year. As a result, we are confident that our CMC activities are on track to support our BLA submission in step with the pivotal data readout.

此外，在 2026 年第一季，我們與 FDA 舉行了 Type C 會議，FDA 認可我們所提之製程性能確認（Process Performance Qualification，PPQ）批次活動策略，以支持我們規劃中的 BLA 申請提交。我很高興分享，我們已於 4 月使用 TSHA-102 的商業化製造製程啟動 BLA 申請所需的 PPQ 批次活動，並預期於今年第四季完成全部執行。因此，我們有信心我們的 CMC 活動正按計畫推進，可配合關鍵性數據讀出時點支持 BLA 申請提交。

As a reminder, the FDA previously agreed that TSHA-102 material produced from the clinical and final commercial manufacturing processes are comparable and, therefore, may support our ability to utilize the clinical data across all clinical studies in our TSHA-102 development program in our BLA submission. The ability to leverage the totality of evidence to support the long-term clinical benefit of TSHA-102 would strengthen the overall package and support a potentially expedited BLA submission based on the six-month interim analysis.

提醒各位，FDA 先前已同意由臨床製造製程與最終商業化製造製程所生產之 TSHA-102 物料具有可比性，因此可支持我們在 BLA 申請中，於 TSHA-102 開發計畫的所有臨床研究中使用臨床數據。能夠運用整體證據來支持 TSHA-102 的長期臨床效益，將強化整體申請資料包，並支持基於六個月期中分析而可能加速的 BLA 提交。

Turning to our clinical progress. We further advanced dosing in the REVEAL pivotal trial, with multiple patients dosed across multiple clinical trial sites. In parallel, enrollment in the INSPIRE (sic - ASPIRE) trial is ongoing across multiple sites, and we remain on track to complete dosing in both trials this quarter. I am pleased to share that both high- and low-dose TSHA-102 continue to be generally well tolerated, with no treatment-related serious adverse events or dose-limiting toxicities observed in all patients treated across the REVEAL Phase 1/2 and REVEAL pivotal trials as of the May 2026 data cutoff. We look forward to reporting longer-term data from all 12 pediatric, adolescent, and adult patients treated in Part A of the REVEAL Phase 1/2 trials later this quarter.

接著談我們的臨床進展。我們在 REVEAL 關鍵性試驗中進一步推進給藥，已有多名患者在多個臨床試驗中心完成給藥。同時，INSPIRE（原文如此—ASPIRE）試驗在多個中心持續招募中，我們仍按計畫於本季完成兩項試驗的給藥。我很高興分享，截至 2026 年 5 月數據截止日，在 REVEAL 第 1/2 期與 REVEAL 關鍵性試驗中接受治療的所有患者中，高劑量與低劑量 TSHA-102 整體而言持續具有良好耐受性，未觀察到與治療相關的嚴重不良事件或劑量限制性毒性。我們期待於本季稍晚，報告 REVEAL 第 1/2 期試驗 A 部分中接受治療之 12 名兒科、青少年與成人患者的更長期數據。

Our pivotal development strategy is grounded on the rigor of our natural history analysis and Part A data collection and evaluation, with trial design, endpoints, and statistical analyses developed based on discussions and written feedback from the FDA. Accordingly, developmental milestones in Part A are assessed using three structured criteria, all of which must be met in order for a developmental milestone to qualify as a gain or a regain post-TSHA-102.

我們的關鍵性開發策略，建立在自然病程分析以及 A 部分數據收集與評估的嚴謹性之上；試驗設計、終點與統計分析係基於與 FDA 的討論及其書面回饋所制定。因此，A 部分中的發展里程碑係以三項結構化標準進行評估，且必須同時符合三項標準，該發展里程碑方可在 TSHA-102 治療後被認定為「獲得」或「恢復」。

First, all caregivers must complete the clinician-administered historical milestone questionnaire used in the natural history study. This allows us to identify milestones eligible for gain or regain by confirming whether a milestone was never previously achieved or was lost long enough ago that the likelihood of a spontaneous gain or regain is less than 6.7%.

第一，所有照護者必須完成自然病程研究中使用的、由臨床人員施測的歷史里程碑問卷。這使我們能透過確認某一里程碑是否從未達成，或是否在足夠久之前已喪失以致自發性獲得或恢復的機率低於 6.7%，來辨識符合「獲得」或「恢復」資格的里程碑。

Establishing a documented time-sense loss is fundamental to accurately differentiate a true regain from natural variability, as each of the 28 milestones has its own determinant. A simple baseline assessment is not sufficient documentation to support a rigorous statistical assessment and is susceptible to false positives. Our approach ensures milestone history is captured accurately so that only true open milestones are counted as gains or regains.

建立具文件佐證的、具時間性的喪失紀錄，是準確區分真正的「恢復」與自然變異的基礎，因為 28 項里程碑各自有其判定要素。僅以簡單的基線評估並不足以作為支持嚴謹統計評估的文件佐證，且容易產生偽陽性。我們的方法可確保里程碑歷史被準確記錄，使得只有真正開放的里程碑才會被計入為「獲得」或「恢復」。

Second, the milestone gain must be captured by post-treatment video documentation. This provides evidence of milestone gains that can be objectively reviewed, which brings me to the third criterion. Video evidence must be independently evaluated by multiple external raters using a pre-specified definition of achievement for each milestone from our pivotal trial protocol.

第二，里程碑增益必須透過治療後的影片紀錄加以捕捉。這提供了可供客觀審查的里程碑增益證據，這也引出第三項標準。影片證據必須由多位外部獨立評分者，依據我們關鍵性試驗方案中對各里程碑達成的預先指定定義進行評估。

We believe these criteria are essential for interpreting functional outcomes and provide a reliable assessment of TSHA-102's efficacy as we advance towards registration. We believe our Part A data accurately reflect the outcomes we expect to observe in the pivotal trial, as they are evaluated using the same FDA-aligned criteria for the pivotal trial protocol.

我們認為這些標準對於解讀功能性結果至關重要，並在我們邁向註冊申請之際，提供對 TSHA-102 療效的可靠評估。我們相信我們的 A 部分數據能準確反映我們預期在關鍵性試驗中觀察到的結果，因為其係以與關鍵性試驗方案相同、且與 FDA 對齊的標準進行評估。

As a reminder, we presented data from Part A of the REVEAL Phase 1/2 trials last year, demonstrating an 83% response rate at six months post-treatment, with five of the six patients treated with the high-dose TSHA-102 gaining or regaining at least one developmental milestone. By nine months post-treatment, the data demonstrated a 100% response rate across the six treated high-dose patients.

提醒一下，我們去年公布了 REVEAL 第 1/2 期試驗 A 部分的數據，顯示治療後六個月的反應率為 83%，其中接受高劑量 TSHA-102 治療的六名患者中有五名獲得或重新獲得至少一項發展里程碑。至治療後九個月，數據顯示在六名接受高劑量治療的患者中反應率達到 100%。

In addition to the 22 developmental milestones gained across the 10 patients treated with TSHA-102, patients also demonstrated a total of 165 additional functional skills and improvements across the core domains of Rett syndrome, an average of approximately 19 functional gains per patient. We observed a consistent pattern of early gains that were sustained, with additional gains seen over time, demonstrating the deepening of effect.

除 10 名接受 TSHA-102 治療的患者共獲得 22 項發展里程碑外，患者亦在雷特氏症核心領域中展現合計 165 項額外功能技能與改善，平均每位患者約 19 項功能增益。我們觀察到一致的早期增益模式且得以維持，並隨時間出現更多增益，顯示療效加深。

In our upcoming Part A data readout, we expect to report longer-term follow-up, including at least 12 months of data from all 12 patients treated with TSHA-102. These results will include functional gains based on natural history-defined developmental milestones and additional functional skills and improvements impacting the activities of daily living that are meaningful to the caregivers and clinicians. We will be hoping to see a consistent pattern of early responses that are sustained and deepen over time across functional gains and clinical outcome measures in the treated patients.

在即將公布的 A 部分數據讀出中，我們預期將報告更長期的追蹤結果，包括所有 12 名接受 TSHA-102 治療患者至少 12 個月的數據。這些結果將包含基於自然病程所定義之發展里程碑的功能增益，以及影響日常生活活動、對照護者與臨床醫師具有意義的額外功能技能與改善。我們希望看到在受治療患者中，早期反應呈現一致模式且可維持，並隨時間在功能增益與臨床結果指標上持續加深。

We believe this longer-term follow-up will provide important context around the durability, deepening of effect, and consistency in responses. With FDA alignment on the potential to pool data across the full TSHA-102 development program in our BLA submission, we believe the longer-term Part A data has the potential to strengthen the overall BLA package and support an expedited submission.

我們認為這項較長期的追蹤將就療效持久性、療效加深以及反應一致性提供重要脈絡。在 FDA 對於於 BLA 申請中可跨整個 TSHA-102 開發計畫彙整數據的潛力達成一致的情況下，我們相信較長期的 A 部分數據有潛力強化整體 BLA 資料包並支持加速提交。

In parallel to our clinical and regulatory execution, we continue to build out our internal commercial infrastructure. We have strategically assembled a strong commercial leadership group, including senior hires who have deep expertise in commercial strategy, pre-commercial, and product launch planning, as well as payer and healthcare systems engagement within the gene therapy space. With these key roles now in place, we are focused on developing a strategic commercial strategy to prepare for a potential launch, and we expect to share additional details on our commercial plans in the second half of the year.

在推進臨床與法規執行的同時，我們也持續建置內部商業化基礎設施。我們策略性地組建了強而有力的商業領導團隊，包括具備深厚商業策略、上市前準備與產品上市規劃，以及在基因治療領域與支付方及醫療體系互動經驗的資深招募人員。隨著這些關鍵職位到位，我們正專注於制定策略性商業策略以為潛在上市做準備，並預期在今年下半年分享更多商業計畫細節。

I would now like to turn the call over to Suku to discuss evidence that further validates the TSHA-102 program and route of administration in more detail. Suku?

接下來我想把電話會議交給 Suku，更詳細討論進一步驗證 TSHA-102 計畫與給藥途徑的證據。Suku？

Thank you, Sean. We have continued to make meaningful progress advancing TSHA-102 towards registration and remain confident in its differentiated potential.

謝謝你，Sean。我們持續在推進 TSHA-102 邁向註冊方面取得具意義的進展，並對其差異化潛力保持信心。

A key design attribute of TSHA-102 is its minimally invasive intrathecal route of administration, which market research shows is strongly preferred by clinicians and caregivers over direct-to-brain central nervous system delivery. This preference is driven by its familiarity, accessibility, and scalability, enabling broad access to treatment across institutions, from major centers of excellence to regional and local sites.

TSHA-102 的一項關鍵設計特徵是其微創的鞘內給藥途徑；市場研究顯示，相較於直接進入腦部的中樞神經系統遞送方式，臨床醫師與照護者更明顯偏好此途徑。此偏好源於其熟悉性、可近性與可擴展性，使治療能在各類機構廣泛提供，從大型卓越中心到區域與地方據點皆可施行。

A peer-reviewed article was recently published by Frontiers in Medicine – Gene and Cell Therapy, which highlights preclinical data we previously presented at the 2025 International Rett Syndrome Foundation Rett Syndrome Scientific Meeting. The data showed that intrathecal and direct-to-brain intra-cisterna magna administration demonstrated comparable, consistent, and widespread distribution of AAV9 vector throughout the brain and spinal cord in non-human primates. We believe this further validates lumbar intrathecal delivery as a potentially safe, effective, and minimally invasive approach to deliver a gene therapy to the central nervous system.

Frontiers in Medicine – Gene and Cell Therapy 近期發表了一篇同儕審查文章，重點介紹我們先前在 2025 年國際雷特氏症基金會雷特氏症科學會議上發表的臨床前數據。數據顯示，在非人靈長類中，鞘內給藥與直接進入腦部的枕大池內（intra-cisterna magna）給藥，皆可在腦與脊髓中呈現可比、穩定且廣泛的 AAV9 載體分布。我們相信這進一步驗證腰椎鞘內遞送作為將基因治療遞送至中樞神經系統的一種可能安全、有效且微創的方法。

In addition, on May 14, we plan to present new preclinical data that further validates the construct design of TSHA-102 at the ASGCT 2026 Annual Meeting. Consistent with previously published vector comparisons, the data demonstrated that the self-complementary AAV9 vector enables significantly higher protein expression compared to single-stranded AAV9 in neuronal mouse cell models. The 30-fold higher transduction efficiency demonstrated in this study, along with the improved genomic stability of self-complementary AAV9, supports our ability to effectively deliver TSHA-102 to the central nervous system using a minimally invasive lumbar intrathecal administration.

此外，我們計畫於 5 月 14 日在 ASGCT 2026 年會上發表新的臨床前數據，以進一步驗證 TSHA-102 的構築體設計。與先前已發表的載體比較結果一致，數據顯示自互補型 AAV9 載體在神經元小鼠細胞模型中，相較於單股 AAV9 可達到顯著更高的蛋白表達。本研究所示 30 倍更高的轉導效率，加上自互補型 AAV9 改善的基因組穩定性，支持我們能以微創的腰椎鞘內給藥方式，將 TSHA-102 有效遞送至中樞神經系統。

In addition, the data showed that the mini-MECP-2 protein used in our TSHA-102 construct was functionally comparable to the full-length MECP2 protein across molecular and biochemical functions. We believe these data support the strategic TSHA-102 construct design and provides important transitional context for the early, sustained, and deepening functional gains demonstrated across all patients previously reported in Part A of the REVEAL Phase 1/2 trials.

此外，數據顯示我們 TSHA-102 構築體所使用的 mini-MECP-2 蛋白，在分子與生化功能層面上與全長 MECP2 蛋白具有可比的功能。我們相信這些數據支持 TSHA-102 的策略性構築體設計，並為先前在 REVEAL 第 1/2 期試驗 A 部分所報告、所有患者皆呈現的早期、可維持且隨時間加深的功能增益提供重要的轉譯脈絡。

We believe the supportive evidence of a continued FDA alignment on a registrational path and the clinical data generated to date support the potential for TSHA-102 to provide meaningful benefits to pediatric, adolescent, and adult patients with Rett syndrome using a minimally invasive delivery approach that is scalable. Our focus remains on clinical execution and data generation as we work to complete dosing in our REVEAL pivotal and ASPIRE trials and report long-term data from Part A of our REVEAL Phase 1/2 trials this quarter.

我們認為，持續與 FDA 對齊的註冊路徑之支持性證據，以及迄今產生的臨床數據，支持 TSHA-102 透過可擴展的微創遞送方式，為罹患雷特氏症的兒科、青少年與成人患者帶來具意義的效益之潛力。我們的重點仍在臨床執行與數據產出，並致力完成 REVEAL 關鍵性試驗與 ASPIRE 試驗的給藥，同時於本季公布 REVEAL 第 1/2 期試驗 A 部分的長期數據。

I would now like to turn the call over to Kamran to discuss financial results.

接下來我想把電話會議交給 Kamran，說明財務結果。

Thank you, Suku.

謝謝你，Suku。

Research and development expenses were $33.8 million for the three months ended March 31, 2026, compared to $15.6 million for the three months ended March 31, 2025. The $18.2 million increase was primarily driven by the BLA-enabling PPQ manufacturing initiatives performed during the three months ended March 31, 2026, and higher clinical expenses from the REVEAL Part A, Phase 1/2, Part B pivotal, and ASPIRE trials. Compensation expenses, including non-cash stock-based compensation, also increased as a result of additional research and development headcount.

截至 2026 年 3 月 31 日止三個月，研發費用為 3,380 萬美元，較截至 2025 年 3 月 31 日止三個月的 1,560 萬美元增加。增加的 1,820 萬美元主要由截至 2026 年 3 月 31 日止三個月期間所進行、用以支援 BLA 的 PPQ 製造計畫所帶動，並且 REVEAL A 部分、第 1/2 期、B 部分關鍵性試驗以及 ASPIRE 試驗的臨床費用較高。由於研發人力增加，包含非現金之股票基礎薪酬在內的薪酬費用亦有所上升。

General and administrative expenses were $9.7 million for the three months ended March 31, 2026, compared to $8.2 million for the three months ended March 31, 2025. The increase of $1.5 million was primarily due to higher compensation expenses, including non-cash stock-based compensation expense and increases in consulting and professional fees, including commercial launch readiness initiatives.

截至 2026 年 3 月 31 日止三個月，一般及行政費用為 970 萬美元，較截至 2025 年 3 月 31 日止三個月的 820 萬美元增加。增加的 150 萬美元主要由較高的薪酬費用所致（包括非現金之股票基礎薪酬費用），以及顧問與專業服務費用增加（包括商業上市準備相關計畫）。

Net loss for the three months ended March 31, 2026, was $42.4 million, or $0.12 per share, compared to a net loss of $21.5 million, or $0.08 per share, for the three months ended March 31, 2025.

截至 2026 年 3 月 31 日止三個月，淨損為 4,240 萬美元，或每股 0.12 美元；相較之下，截至 2025 年 3 月 31 日止三個月淨損為 2,150 萬美元，或每股 0.08 美元。

As of March 31, 2026, Taysha had $276.6 million in cash and cash equivalents. We expect that our current cash resources will be sufficient to fund planned operating expenses into 2028.

截至 2026 年 3 月 31 日，Taysha 持有的現金及約當現金為 2.766 億美元。我們預期目前的現金資源足以支應計畫中的營運支出至 2028 年。

I will now turn the call over to Sean for his closing remarks. Sean?

我現在把電話交給 Sean，請他做結語。Sean？

Thank you, Kamran.

謝謝你，Kamran。

Our confidence in our differentiated TSHA-102 gene therapy candidate continues to strengthen based on the developments highlighted today, and we continue to believe TSHA-102 has the potential to deliver meaningful therapeutic benefit to a broad population of patients with Rett syndrome using a minimally invasive delivery approach. With a favorable tolerability profile demonstrated to date, dosing in the REVEAL pivotal and ASPIRE trials on track for completion in the second quarter of 2026 and a well-defined regulatory and commercial path, we're advancing toward potential registration with clarity as we work to bring a potentially transformative therapy to the Rett community.

基於今天重點提到的進展，我們對具差異化的 TSHA-102 基因治療候選產品的信心持續增強；我們也持續相信，TSHA-102 透過微創的給藥方式，有潛力為廣泛的雷特氏症患者族群帶來具意義的治療效益。在目前已展現良好耐受性概況、REVEAL 關鍵性試驗與 ASPIRE 試驗的給藥預計於 2026 年第二季完成，以及明確的法規與商業化路徑之下，我們正以清晰的方向推進至潛在註冊申請，並努力為雷特氏症社群帶來可能具變革性的療法。

I will now ask the operator to begin our Q&A session. Operator?

我現在請接線員開始我們的問答環節。接線員？

(Operator Instructions) Kristen Kluska, Cantor.

(接線員指示) Cantor 的 Kristen Kluska。

Hi. Good morning, everybody, and congrats on these updates. So I wanted to ask you a little bit more about some of the data you're going to have at ASGCT. For the work you're doing that supports higher MECP2 protein expression with the self-complementary AAV9, can you tell us why this matters so much versus the obvious of just having more protein expression? Does this allow for a greater orchestra effect across more neurons? Does it mean a faster onset of action? What would you truly highlight here?

嗨。各位早安，恭喜這些更新。我想再多問一些你們將在 ASGCT 發表的部分數據。針對你們所做、支持以自互補 AAV9 提高 MECP2 蛋白表達的工作，你們能否說明為什麼這件事如此重要，而不只是「蛋白表達更多」這個顯而易見的理由？這是否能在更多神經元之間產生更強的協同（orchestra）效應？是否代表起效更快？你們真正想強調的重點是什麼？

Thanks for the question, Kristen. I think Suku and I can tag team this.

謝謝你的問題，Kristen。我想我和 Suku 可以一起回答。

But at a high level, I think what we wanted to do was really provide the why as to what the clinical result that we're generating is. I mean, from a clinical perspective, in every patient treated, whether it's a pediatric patient, adolescent patient, adult patient, everyone has been a responder. We're seeing multiple skills and improvements across all of these patients. And they happen quickly, and then they improve over time and get deeper.

但從高層次來看，我認為我們真正想做的是說明「為什麼」我們能產生目前的臨床結果。從臨床角度而言，每一位接受治療的患者，不論是兒科、青少年或成人，全部都是反應者。我們在所有這些患者身上看到多項能力與改善。而且改善發生得很快，之後會隨時間持續進步、幅度更深。

And so the question is, why does that occur? And I think what we're highlighting at ASGTC is the fact that the construct, which we purposely utilize self-complementary technology, ultimately drives in this dataset a 30 times transduction efficiency or protein expression than single strand does. And so that is a reason why you could potentially use a less invasive route of administration like intrathecal versus having to go with a closer to the brain approach and usually you have to do that because of a single strand.

所以問題是：為什麼會這樣？我想我們在 ASGTC 強調的是：這個載體設計中，我們刻意採用自互補技術，在這組數據中最終帶來相較於單股（single strand）高出 30 倍的轉導效率或蛋白表達。因此，這也是為什麼你可能可以使用較不侵入性的給藥途徑，例如鞘內（intrathecal），而不必採取更接近腦部的給藥方式；通常之所以需要那樣做，是因為使用單股載體。

The other thing too is just reinforcing the fact that the mini-MECP2 gene continues to show comparability. It's been published for over 15 years that this has been the case. But again, we just wanted to highlight that regardless of the genotype that we're seeing in these 12 patients that we've dosed to date and that we'll report on in a few weeks, they're all responding and they're responding across clinical domains.

另外一點是再次強化：mini-MECP2 基因持續展現可比性。這點在文獻上已發表超過 15 年。但我們仍想再次強調：不論我們在目前已給藥的 12 位患者（我們將在幾週後報告）中看到何種基因型，他們都在反應，而且是在多個臨床領域都有反應。

And the gene, the mini gene, is very much a part of that because it essentially equals the full-length gene. And again, the reason that we use the mini gene was so we could package the self-comp. So we're just trying to highlight the fact that the reason -- all the reasons that we put into building the construct are being demonstrated clinically and that this allows us to use a particular route of administration that we know is strongly preferred out in the community.

而這個基因、這個 mini 基因，在其中扮演非常重要的角色，因為它本質上等同於全長基因。再次說明，我們使用 mini 基因的原因，是為了能夠封裝自互補（self-comp.）。所以我們只是想強調：我們在建構這個載體時所投入的各項理由，正在臨床上被證實；而這也讓我們能採用一種我們知道在社群中明顯更受偏好的給藥途徑。

Suku, I don't know if there's more you might want to add to that.

Suku，我不確定你是否還想補充。

Yes, Sean, I have a few more points to add. So Kristen, thanks for that incredibly important question.

是的，Sean，我還有幾點要補充。Kristen，謝謝你提出這個非常重要的問題。

What we've already shown with our REVEAL Part A program is that a simple lumbar puncture, a self-complementary mini gene construct using TSHA-102 gives you incredibly important clinical results from an efficacy standpoint that translates into a significant improvement in activities of daily living. So the clinical data at the present time from Part A now speaks for itself.

我們在 REVEAL A 部分計畫中已經顯示：透過一次簡單的腰椎穿刺，使用 TSHA-102 的自互補 mini 基因載體，就能在療效面帶來極其重要的臨床結果，並轉化為日常生活活動能力的顯著改善。因此，就目前而言，A 部分的臨床數據本身已足以說明一切。

So now, when we work backwards and continue to further look at preclinical data, whether it's ours or from other companies, it is very clear that a self-complementary construct turns on very quickly once given into the central nervous system, i.e., via the CSF. Once it turns on, it has rapid impact on one of the most important components of Rett syndrome, which is the autonomic dysfunction component, where we have impact pretty quickly, usually within a couple of weeks post-dosing. We've also shown repeatedly now in Part A that we have very positive clinical impact consistently, regardless of age, genotype, or phenotypic presentation of the patients with Rett syndrome, where there is an improvement in gross motor, fine motor skills, or restoration of those skills which have been lost over time, but also improvement in the ability to communicate as well as when it comes to social activities.

因此，當我們回推並持續深入檢視臨床前數據（不論是我們自己的或其他公司的），可以非常清楚地看到：自互補載體一旦給入中樞神經系統，也就是經由腦脊髓液（CSF），就會非常快速地啟動表達。一旦啟動，它會迅速影響雷特氏症最重要的組成之一，也就是自律神經功能失調（autonomic dysfunction）這一部分；我們通常在給藥後幾週內就能很快看到影響。我們也在 A 部分反覆證明：不論年齡、基因型或雷特氏症患者的表型表現，我們都能一致地看到非常正向的臨床影響，包括粗大動作、精細動作技能的改善，或是恢復那些隨時間流失的技能；同時也改善溝通能力以及社交活動表現。

So my point here is that a self-complementary stable construct turns on quickly, it persists and it continues to persist and build on top of all the preclinical data that we have that shows that a lumbar puncture with the right product can have a simple but consistent positive clinical response for a post-patient population that has significant unmet medical data, in this case Rett syndrome. And I think we may have set the stage for an intrathecal lumbar puncture-based platform to treat difficult CNS diseases.

所以我在這裡要說的是：一個自互補且穩定的載體會快速啟動、並且能持續存在；再加上我們所有臨床前數據所顯示的結果——透過腰椎穿刺、搭配正確的產品，就能在一個具有重大未被滿足醫療需求的患者族群（此處為雷特氏症）中，帶來簡單但一致的正向臨床反應。我認為我們可能已為一個以鞘內腰椎穿刺為基礎的平台奠定基礎，用以治療困難的中樞神經系統疾病。

Thank you.

謝謝。

Salveen Richter, Goldman Sachs.

高盛的 Salveen Richter。

Good morning. Regarding the BLA submission pathway for 102, can you walk through the different scenarios here and whether approval based on the six-month data should be considered the base case assumption and how you characterize the willingness of the FDA to approve based on six-month data sets and timelines around this? That would be great. Thank you.

早安。關於 102 的 BLA 申請遞交路徑，你能否帶我們走一遍不同情境，以及是否應將基於 6 個月數據獲批視為基本情境假設？另外，你如何描述 FDA 對於基於 6 個月數據集進行核准的意願，以及相關時間表？那會很有幫助。謝謝。

Yes, Salveen. Great question. We've been out talking with the investment community really since the beginning of the year, and this topic has come up. And so I think those that are on the call, this will sound very familiar, but we were very transparent with the FDA. Part of this meeting was trying to gain alignment, and we were walking them through various scenarios. And we told them point blank that our preferred scenario would be a full approval at six months' worth of data.

好的，Salveen。很好的問題。我們自今年年初以來一直與投資社群溝通，這個主題也常被提到。所以對於在電話會議上的各位來說，這聽起來會很熟悉：我們對 FDA 非常透明。這次會議的一部分目的就是爭取一致性，我們也向他們說明了各種情境。我們也直接明確告訴他們：我們偏好的情境，是以 6 個月的數據取得完整核准（full approval）。

And the argument for that, I mean, generally, they like the precedent of 12 months of data for gene therapy, which is arguably probably pretty arbitrary, to be honest, but that's generally what they've held to. And I think our perspective on that is understood. But if we continue to demonstrate comparability with Part A, we're going to have years of data from those patients that we can use to support the durability.

而支持這點的論述是：一般而言，他們偏好基因治療有 12 個月數據的先例；老實說，這可能相當武斷，但這確實是他們通常遵循的標準。我想我們對此的觀點他們是理解的。但如果我們能持續證明與 A 部分的可比性，我們將擁有來自那些患者的多年數據，可用來支持療效持久性（durability）。

And their answer was essentially, ultimately, this is going to come down to the totality of the evidence. And this is something that if the company chooses to do, we are open to it and we will review that in due course. Which is really the best answer you could possibly get, which is doors open, but let the data speak for itself.

而他們的回覆基本上是：最終這將取決於整體證據（totality of the evidence）。如果公司選擇這麼做，他們是開放的，並會在適當時點進行審查。這其實是你能得到的最佳答案：大門是開的，但讓數據自己說話。

The second derivative of that, in our view, was basically, if for whatever reason the FDA decides that -- let's just say they want to keep it as a precedent at 12 months, we would push hard for a rolling review because the CMC modules would be done, the preclinical modules would be done, and we can have things updated where the six-month data is packaged in a way that they could look at that. And also -- then there's less to review when you would submit the final 12-month data, and that can pull things forward a couple of quarters.

在我們看來，其次衍生的重點基本上是：如果因任何原因 FDA 決定——比方說，他們想把它維持為 12 個月的先例，我們會強力爭取採用滾動式審查，因為 CMC 模組會完成、臨床前模組也會完成，而且我們可以把六個月數據以他們能夠審視的方式打包並更新。另外——如此一來，當你提交最終 12 個月數據時，需要審查的內容就更少，這可以把時程往前拉動幾個季度。

And then obviously, the third scenario would be there may be nothing at all wrong with the data, they just want to see 12 months. So we feel in any of those scenarios, number one, there continued to be a positive and constructive dialogue with the agency. There was no opposition to anything that we put forward. There was an openness to it. Clearly, it's going to come down to the totality of the evidence and their comfort level around the data package that's put forward.

然後很顯然，第三種情境可能是數據本身完全沒有任何問題，他們只是想看到 12 個月。所以我們認為在任何一種情境下，第一，與主管機關之間都持續保持正向且具建設性的對話。對於我們提出的任何內容，都沒有遭到反對。他們對此是開放的。顯然，最終將取決於證據的整體性，以及他們對所提交數據包的安心程度。

But as we've said all along, the nice thing about this six-month interim is it creates the optionality for us to potentially get this to patients faster. And my personal opinion, I can be wrong, is that almost regardless of what we come back with, I know everyone would prefer it's the fastest time point, and obviously, we're going to do everything we can to facilitate that, but we'll have clarity for the market.

但正如我們一路以來所說，這個六個月期中分析的好處在於，它為我們創造了選擇性，讓我們有可能更快把治療帶給病患。而我個人的看法——我可能會錯——是幾乎不論我們回來的結果是什麼，我知道大家都偏好最快的時間點，當然我們也會盡一切努力促成，但我們會讓市場獲得明確性。

And even in the scenario -- and don't read into this, it's just even in the scenario where it's a 12-month ask, we can say that, and you know what our six-month data are, and people can judge the probability of success, and then it's an execution story. So for all the reasons that we laid out in this call, we feel that there is strong evidence to push for the six-month data. The fact that we've got comparability with the FDA on the CMC side is absolutely critical to this. And that opens the door for us to pool the Part A data alongside the pivotal Part B and, in our opinion, really should alleviate any concerns on the durability piece.

即便在那種情境——別過度解讀，我只是說即便在需要 12 個月數據的情境下——我們也可以這麼說，而且你也知道我們的六個月數據是什麼，大家可以自行判斷成功機率，接下來就是執行的故事。因此，基於我們在本次電話會議中闡述的所有理由，我們認為有強而有力的證據可以推動採用六個月數據。我們在 CMC 端與 FDA 已達成可比性（comparability），對此至關重要。而這也為我們打開大門，得以將 A 部分（Part A）數據與關鍵性 B 部分（pivotal Part B）合併分析，並且在我們看來，確實應能緩解任何對持久性（durability）的疑慮。

So ultimately, we'll leave it at that. The nice thing is we've got this option, these options in front of us, thanks to the data that we've put forward today and also the CMC quality that we've put forward today. So we're in the best possible position we can be. We've got a couple cards that can fall our way, and we're excited about having this discussion with the FDA at the appropriate time.

所以最終，我們就先說到這裡。好的一點是，因為我們今天提出的數據，以及我們今天提出的 CMC 品質，我們面前有這個選項、這些選項。因此我們處於我們所能達到的最佳位置。我們手上有幾張牌可能會朝有利方向發展，我們也很期待在適當的時間與 FDA 進行這場討論。

Thank you.

謝謝。

Thank you.

謝謝。

Biren Amin, Piper Sandler.

Piper Sandler 的 Biren Amin。

Yeah. Hi, guys. Thanks for taking my questions. Recently, the FDA commissioner announced a real-time clinical monitoring program that enables the FDA to evaluate data real time. Is that something that the company can leverage for REVEAL, given the high unmet need in Rett syndrome, especially, Sean, with the six-month data and the agency potentially following patient data to 12 months during review under this program? So I guess that's the first question.

是的。嗨，各位。謝謝回答我的問題。最近，FDA 局長宣布了一項即時臨床監測計畫，讓 FDA 能夠即時評估數據。鑑於雷特氏症（Rett syndrome）存在高度未被滿足的需求，這是否是公司可以用於 REVEAL 的機制？尤其是，Sean，若以六個月數據為基礎，並在該計畫下於審查期間讓主管機關持續追蹤病患數據到 12 個月？所以我想這是第一個問題。

And then second question for REVEAL, do you expect to stop enrollment at 15 patients, or could you potentially over-enroll as is typically the case with clinical trial management and execution? And if that's the case, how does the over-enrollment impact the effect size calculation for the study? Thank you.

第二個問題是關於 REVEAL：你們預期會在 15 名病患時停止收案，還是可能像臨床試驗管理與執行通常那樣，出現超額收案？如果是這樣，超額收案會如何影響本研究的效應量（effect size）計算？謝謝。

Yeah, just real quickly on the real-time piece, I'll ask Suku to comment on that. But I would say we're always keeping our eyes open for what we could potentially do. The other one is the commissioner's voucher, right? Things are so dynamic up there, it can be difficult sometimes to tell what's afforded to you and what's not afforded to you.

好的，關於即時（real-time）那一塊，我先請 Suku 來評論。但我想說的是，我們一直都在留意有哪些事情是我們可能可以做的。另外還有局長的代金券（voucher），對吧？那邊的情況非常動態，有時候很難判斷哪些是你能獲得的、哪些不是。

I think that what I just laid out in terms of scenarios, we feel very good about. If there's an opportunity for us to lever one of these additional pathways, sure, we would try to do that. But again, I don't want to try to make it sound like that's what we're attempting to do out of the gate here, just because it's not as formalized and crystallized in terms of the timelines, what you need to meet the hurdle bar, et cetera.

我認為，就我剛才所描述的各種情境而言，我們感覺非常良好。如果有機會讓我們運用其中一條額外途徑，當然，我們會嘗試。但同樣地，我不想讓人覺得我們一開始就打算這麼做，因為在時程、你需要達到的門檻標準等方面，它還沒有那麼正式化與明確化。

I don't know if there's anything you'd add to that, Suku.

Suku，你還有什麼要補充的嗎？

Yes, Sean. I mean, Biren, thanks for that very interesting and important question, because what the FDA has proposed, I think, could change the way clinical trials are overseen by the FDA with their direct hands-on experience and oversight. But at the same time, as the real-time data pours in, I think the regulators and the sponsors, clinical regulatory teams will have to work very closely to make sure appropriate interpretation is done when it comes to real-time safety data and efficacy data.

是的，Sean。我的意思是，Biren，謝謝你提出這個非常有趣且重要的問題，因為我認為 FDA 所提出的作法，可能會改變 FDA 以其直接、親身參與與監督的方式來管理臨床試驗。但同時，隨著即時數據不斷湧入，我認為監管單位與申辦方、臨床法規團隊必須非常緊密合作，以確保在解讀即時安全性數據與有效性數據時能做出適當的詮釋。

Because especially in the rare disease space, as you know, we are learning not only about the disease, but also the response to the therapeutic intervention at that point in time, and sometimes, the real-time decisions versus a more time process-oriented decision could have significantly impact and influence on programs. So I hope that helps, because at this time, we are kind of watching the process interestingly and eventually the decision-making governance between the regulators and the sponsor are going to be critical to make sure real-time oversight of clinical trials will pay the dividend that the FDA hopes it will.

因為特別是在罕見疾病領域，如你所知，我們不僅在學習疾病本身，也在學習在那個時間點對治療介入的反應；有時候，即時決策相較於較偏時間流程導向的決策，可能會對計畫造成顯著的影響與左右。所以希望這能有所幫助；因為就目前而言，我們正以高度關注的態度觀察這個流程，而最終監管單位與申辦方之間的決策治理機制將至關重要，以確保臨床試驗的即時監督能帶來 FDA 所期望的效益。

And then the question around the potential for over-enrollment, I would say that you're always trying to balance the -- getting the appropriate patients in screened essentially, understanding that there could potentially be a screen fail, one of the criteria we have is there's a number of open milestones you must have as an example.

然後關於可能超額收案的問題，我會說你總是在平衡——本質上是讓適當的病患進入篩選，同時也要理解可能會出現篩選失敗（screen fail）；例如，我們其中一項條件是必須達到若干開放里程碑（open milestones）。

You could go through the screening and then find out that that patient doesn't quite meet it. So you're going to want to have more patients than 15 going through the screening process. And if you do end up in a situation where you dose an extra patient or two, we would be certainly willing to do that.

你可能完成篩選後才發現該病患並不完全符合。所以你會希望有多於 15 名病患進入篩選流程。而如果最後真的出現多給一到兩名病患給藥的情況，我們當然願意這麼做。

I can just say the effects on the statistics are minimal. I mean, they would obviously look at the first 15 patients first and do the statistics on that. And then if you had another patient or two, they would do the statistics on that, but they really don't change much.

我可以說，對統計的影響很小。我的意思是，他們顯然會先看前 15 名病患，並以此做統計分析。然後如果你又多了一兩名病患，他們也會對那部分做統計，但其實不會改變太多。

Anything else you would add there, Suku?

Suku，你還有什麼要補充的嗎？

Well, the only thing I would add, Sean, is that, as you said, the power and p-values for a patient sample size of 15, if it goes to 16 or 17, based on what Sean just described, it won't have major impact on power of p-value for the study itself. And as you know from REVEAL Part A, we already have 100% responder rate at nine months with a small number of patients. And those observations, I think, are significant.

嗯，我唯一要補充的是，Sean，正如你所說，若病患樣本數為 15，增加到 16 或 17，基於 Sean 剛才描述的情況，對本研究本身的檢定力（power）與 p 值不會有重大影響。而且如你從 REVEAL A 部分（Part A）所知，我們在少數病患中於九個月時已達到 100% 反應者率（responder rate）。我認為這些觀察結果是重要的。

And as you know, all we need is a 33% responder rate for our REVEAL Part B study. So let us see what the eventual data pans out, but I think we are confident that the Part A data hopefully should be reproduced in Part B as well.

如各位所知，我們的 REVEAL B 部分研究只需要 33% 的反應者比例。因此讓我們看看最終數據會如何呈現，但我認為我們有信心，A 部分的數據希望也能在 B 部分得到重現。

Yeah. I think the key, Biren, is just simply that the null hypothesis is so low. It's effectively one patient spontaneously having an effect. So because of that number being such a low aspect, the overall N doesn't really change things very much. But good question. Thank you.

是的。我認為關鍵在於，Biren，虛無假設的門檻非常低。基本上等同於一位病患自發性地出現效果。因此由於這個數字非常低，整體樣本數 N 的變化其實不太會改變結果。不過問得很好。謝謝。

(Operator Instructions) Tazeen Ahmad, Bank of America.

(接線員指示) 美國銀行（Bank of America）的 Tazeen Ahmad。

Hi. Good morning. This is Wesley on for Tazeen. Thanks for the updates today. I had a question on sort of the mechanics of the Part B portion of the study compared to the Part A. Are the assessments being done of the patients, the treated patients, being done in the same way in Part B to Part A? Who was doing the video recordings?

嗨。早安。我是 Wesley，代替 Tazeen 發言。謝謝今天的最新進展。我想問一下，研究 B 部分相較於 A 部分在執行機制上有何不同。B 部分對病患（已治療病患）的評估方式，是否與 A 部分相同？影片錄製是由誰負責？

And with regards to sort of the patients that you are currently screening and plan to dose, are those sort of sites and investigators similar between Part B and Part A? I'm just trying to look for any color and straight lines we can draw from the 12-month update you're going to share soon to what we can expect and how the Part B is running. Thank you.

另外，關於你們目前正在篩選並計畫給藥的病患，B 部分與 A 部分的試驗中心與研究者是否大致相同？我只是想了解一些背景與可對照的脈絡，看看你們即將分享的 12 個月更新，能讓我們對 B 部分的運作與可預期結果畫出哪些較直接的連結。謝謝。

Good. Thanks for the question. And Suku, we can tag team this.

好的。謝謝你的問題。Suku，我們可以一起回答。

Our view is that the read-through from the upcoming data review that we're going to put out should be pretty direct for all of you. And that's why we put so much emphasis around the rigor of the data collection in Part A. We spent a lot of time on the call talking about that.

我們的看法是，我們即將發布的數據審查結果，對各位而言應該會是相當直接的延伸解讀（read-through）。這也是為什麼我們如此強調 A 部分資料收集的嚴謹性；我們在電話會議上花了很多時間談這件事。

And it starts with the fact that, number one, what we rate is -- so first of all, all of our milestones for the primary endpoint are pre-specified. There's clear definitions for those. And those demonstrations are from videos that are conducted in the study itself. So when people -- the way it's been working is that people are doing the hand function test or the RMBA or the Mullen.

而這首先從一點開始：第一，我們評分的內容是——也就是說，我們主要終點的所有里程碑都是事先預先指定（pre-specified）的。這些都有明確定義。而這些達成的證據來自於研究中所拍攝的影片。因此當受試者——目前的運作方式是，受試者會進行手部功能測試或 RMBA 或 Mullen。

If we have video of them doing a milestone, that video then goes outside the company, and two of three raiders have to adjudicate that as a milestone. So the company has nothing to do with what is declared a milestone. And I think that has been a big part of the reason why the agency has been open to our data set and the interim analysis is that we had rigorous video evidence that was adjudicated outside the company.

如果我們有他們完成某個里程碑的影片，該影片就會送到公司外部，並且三位評分者中需有兩位裁定（adjudicate）其符合里程碑。因此公司本身與「是否宣告為里程碑」完全無關。我認為這也是主管機關願意接受我們的資料集與期中分析的一大原因：我們有嚴謹的影片證據，且由公司外部進行裁定。

Now, the other side of this coin is that the Mullen, which is another videotape demonstration, and the RMBA are also supportive data sets that the agency sees. Again, those are on video. The Mullen also gets centrally adjudicated and the FDA -- and the RMBA is done in the clinic by the physician. So there's no real way to be putting your thumb on a scale and making this data subjective. It's very objective.

另外一面是，Mullen（同樣是另一種錄影示範）以及 RMBA 也都是主管機關所看到的支持性資料集。同樣地，這些都有影片。Mullen 也會進行中央裁定（centrally adjudicated），而 FDA——至於 RMBA 則是在診間由醫師執行。因此幾乎沒有辦法「偏袒」或讓這些數據變得主觀。這是非常客觀的。

So I think this is a good read-through to Part B. The only difference in Part B is that we're going to have a standalone assessment of all of the milestones. So I would argue that we're probably undercounting milestones in Part A and that we have a better chance of counting more milestones in Part B because there's a standalone test. We spent a lot of time with the FDA developing this test. We have training modules around this test.

所以我認為這對 B 部分是很好的延伸解讀。B 部分唯一的差異在於，我們將對所有里程碑進行獨立的單獨評估（standalone assessment）。因此我會主張，我們在 A 部分可能反而低估了里程碑數，而在 B 部分因為有獨立測試，反而更有機會捕捉到更多里程碑。我們花了很多時間與 FDA 一起開發這項測試。我們也針對這項測試建立了訓練模組。

The test is conducted in the hospital by trained assessors at the hospital. So this is not done at home. The parents aren't doing this. Is very prescriptive and it's done in-house. Those videos then go outside the hospital to the raters where they remain blinded until they break -- until the six-month time period where they break the blind for all of the 15 patients and review those videos.

該測試是在醫院由受過訓練的評估人員執行。因此不是在家中進行。也不是由家長執行。流程非常明確且具規範性，並在院內完成。這些影片之後會從醫院送到外部評分者手上，評分者會維持盲態，直到——直到六個月的時間點，才會對全部 15 位病患解盲並審查這些影片。

So the whole point of what we've been trying to emphasize since we began reporting data on milestones is clear definitions, rigorous baseline collection with videos assessed by central raters, it's going to be very similar in Part B, but even more rigorous, and I think there's more ability to capture milestones because we now have a standalone test. So hopefully, that gives you a perspective there, but I think the read-throughs should be pretty direct when we update you in a few weeks.

因此，自從我們開始報告里程碑數據以來，我們一直強調的重點是：明確定義、以影片進行嚴謹的基線收集並由中央評分者評估。B 部分會非常類似，但更為嚴謹；而且因為現在有獨立測試，我認為捕捉里程碑的能力更強。希望這能提供你一些視角；不過我認為幾週後我們更新時，延伸解讀應該會相當直接。

Got it. Thanks for the detail. Thank you.

了解。謝謝你提供這麼詳細的說明。謝謝。

You're welcome.

不客氣。

Maury Raycroft, Jefferies.

Jefferies 的 Maury Raycroft。

Hi. This is James on for Maury. Thanks for taking our question. For the 12-plus months of follow-up in the 2Q update, how are you setting expectations for the early milestones and skills deepening versus new, more complex milestones and skills appearing between 6 and 12 months? And how do you plan to communicate that in the update relative to the presentation last year?

嗨。我是 James，代替 Maury 發言。謝謝回答我們的問題。針對第二季更新中超過 12 個月的追蹤，你們如何設定市場對早期里程碑與技能深化的預期，相較於在 6 到 12 個月之間出現新的、更複雜的里程碑與技能？以及相較於去年那次簡報，你們打算在這次更新中如何傳達？

And also, should we expect a potential safety update from the REVEAL pivotal cohort around IRSF? Or should we expect that update at a later point after IRSF?

另外，我們是否應該預期 REVEAL 關鍵性（pivotal）隊列在 IRSF 前後會有潛在的安全性更新？還是應該預期在 IRSF 之後較晚的時間點才會更新？

Yeah. To answer your second question first, I mean, even today when we said that as of the March safety cutoff, that was inclusive of the REVEAL Part A and also the pivotal trials and ASPIRE. So that's all the studies that we're running right now. You just got a safety update on no treatment-related SAEs and DLTs, and we'll continue to do that on a quarterly basis.

是的。我先回答你的第二個問題：即使是今天我們提到截至 3 月的安全性資料截止日（safety cutoff），其中已包含 REVEAL A 部分、以及關鍵性試驗與 ASPIRE。也就是我們目前正在進行的所有研究。你剛剛已收到一個安全性更新：沒有與治療相關的嚴重不良事件（SAEs）與劑量限制性毒性（DLTs）；我們也會持續以季度為頻率更新。

And the first part of the question, can you repeat that? I already lost it.

至於第一部分的問題，你可以再重複一次嗎？我已經忘了。

For the 12-plus months follow-up and the Q2 update, how are you setting expectations?

針對超過 12 個月追蹤與第二季更新，你們如何設定預期？

Yeah. I mean, to be very simple, and I'll turn it over to Suku, what we've seen on the reports that we did last time was that there's early responses. There's more responses that occur as time goes on relative to milestones, relative to skills and improvements. And the things that you had, you get better at, and you're also developing new milestones, new skills, and new improvements, that's what we would expect to see at 12 months.

是的。我先簡單說，然後交給 Suku：我們從上次發布的報告中看到的是，早期會出現反應。隨著時間推進，與里程碑、技能與改善相關的反應會更多。你原本已具備的能力會變得更好，同時也會發展出新的里程碑、新的技能與新的改善；這就是我們在 12 個月時預期會看到的。

Yes. Sean, as you have emphasized, what we will communicate is the rapid, consistent, persistent clinical impact of TSHA-102 in patients with Rett syndrome, regardless of genotype, phenotype, or age. And I would also emphasize that we hope that we can continue to show a significant collective improvement in skills, quote-unquote, that per patient could go above the 19 per patient that we disclosed this morning and shown with this segment of the communication.

是的。如 Sean 所強調，我們將傳達的是：TSHA-102 對雷特氏症（Rett syndrome）病患帶來快速、一致且持續的臨床影響，不受基因型、表現型或年齡影響。我也要強調，我們希望能持續展現整體技能的顯著集體改善——所謂「技能」——就每位病患而言，可能高於我們今天早上揭露的每位病患 19 項，並透過這段溝通內容加以呈現。

So just pay attention to that as well, because I think a component of reaching developmental milestones in a validated manner, as we've already discussed and described, which the FDA truly likes. And I'm going to emphasize these are done in a blinded reviewer, expert reviewer fashion and not done at home by caregivers, which usually the FDA has questions around. So I hope that a 12-month-plus data disclosure further enhances the confidence in what TSHA-102 can contribute potentially in a transformative manner to this patient population.

所以也請留意這一點，因為我認為，如同我們先前已經討論並說明的，以經過驗證的方式達成發展里程碑，是 FDA 真正喜歡的一個組成部分。我也要強調，這些評估是以盲態審查員、專家審查的方式完成，而不是由照護者在家中進行；對於後者，FDA 通常會有疑問。因此我希望，12 個月以上的數據揭露能進一步提升外界對 TSHA-102 可能以具變革性的方式為這個病患族群帶來貢獻的信心。

Yeah. I guess the last comment there, James, is that we don't expect to see any type of a plateau. We expect to continue to see improvements and new improvements over time based on the historical disclosures. Thank you.

是的。我想最後補充一句，James，我們不預期會看到任何形式的平台期。根據既往披露的歷史資料，我們預期會隨時間持續看到改善，並出現新的改善。謝謝。

Thank you.

謝謝。

Gil Blum, Needham & Company.

Gil Blum，Needham & Company。

Good morning, and thanks for taking our question. Maybe just another one on the six-month interim, as a clarification, the FDA basically has not given clear feedback as to what it takes about this six-month interim. Would you say that what would dictate the decision here would be the data itself and the 12-month data that you're going to present to the IRSF? Thank you.

早安，謝謝讓我們提問。或許再問一個關於六個月期中資料的問題，作為釐清：FDA 基本上尚未就這個六個月期中資料需要達到什麼標準給出明確回饋。你是否會說，這裡的決策將取決於資料本身，以及你們將向 IRSF 提交的 12 個月資料？謝謝。

Gil, can you repeat that? I honestly didn't quite get the point of the question.

Gil，你可以再說一次嗎？老實說，我沒有完全理解問題的重點。

The point is you haven't really gotten clear FDA feedback as it relates to six months interim. They're actually waiting for the data. Is that fair?

重點是，你們其實還沒有收到 FDA 對於六個月期中資料相關的明確回饋。他們其實是在等資料。這樣說公平嗎？

Yeah. I mean, I think that is fair. I think the clear feedback we got is that it's an option for us, and that's all you can ask for at this particular point in time. They've consistently said, since we put that disclosure out, I guess it was June 25 where we started talking about that, it's always been something that's enabled.

是的。我的意思是，我覺得這樣說是公平的。我認為我們得到的明確回饋是：這對我們而言是一個選項，而在目前這個時間點，你也只能期待得到這樣的回覆。自從我們發布那個揭露之後——我想是 6 月 25 日我們開始談到這件事——他們一直都表示這是可行、可被啟用的。

We just confirmed, and we've gotten a lot of questions from investors like, hey, when's the last time you talked to the FDA? It's like, well, we talked twice in the last few months here, once on CMC and once on our first breakthrough meeting. And we went back through, we got confirmation on the design, on the endpoints, and our scenarios that I went through. And they're like, yeah, I mean, that is an option for you. It's going to depend on the data in terms of approvability. So you're never going to get anything better than that, which is why we were so (technical difficulty) with the outcomes from that meeting.

我們只是再次確認而已，而且我們也收到很多投資人提問，例如：你們上一次跟 FDA 談是什麼時候？我們的回答是：過去幾個月我們談了兩次，一次是 CMC，一次是我們第一次的突破性療法會議。我們回頭把設計、終點，以及我剛剛提到的各種情境都再確認了一遍。他們的回覆是：是的，我的意思是，這對你們來說是一個選項。至於是否可核准，將取決於資料。所以你不會得到比這更好的回覆，這也是為什麼我們對那次會議的結果如此（技術問題）。

Okay. So to summarize, they're open to it.

好的。所以總結一下，他們對此持開放態度。

I didn't hear that.

我沒聽到那句。

Yes, they are open to the six months.

是的，他們對六個月的方案是開放的。

Oh, yeah. And it's in writing, by the way. I mean -- so it's as good as you can get. There was very much an open-mindedness to this, and it's an open door for us at this point in time, and it's going to be won by the data.

喔，是的。而且順帶一提，這是有書面文件的。我的意思是——所以這已經是你能得到的最好程度了。他們對此非常開放，也等於目前為止為我們留了一扇門，而最終將由資料來決定成敗。

Thank you for the clarification. I appreciate it.

謝謝你的釐清。我很感謝。

Thanks. Thanks, Gil.

謝謝。謝謝你，Gil。

(Operator Instructions) Chris Raymond, Raymond James.

(接線員指示) Chris Raymond，Raymond James。

Yeah, thanks. Maybe just two here. Just on the process performance campaign, the PPQ, you mentioned FDA's agreed on equivalency between the clinical and the commercial manufacturing. Maybe just -- can you give a little bit more color on what activities, what are sort of the pinch points, I guess, in terms of getting to having something you can submit in Q4 between now and then?

是的，謝謝。我這邊可能兩個問題。先談製程性能驗證活動（process performance campaign），也就是 PPQ。你提到 FDA 已同意臨床製造與商業化製造之間的等同性。或許能否再多提供一些細節：從現在到你們在第四季能提交資料之間，需要做哪些活動？在我看來，可能有哪些關鍵卡點（pinch points）？

And then, one of the things that kind of struck us, we've done some KOL work where people seem, physicians -- the physician community seems very aware that you have a broad range of ages in your data. Maybe just talk a little bit more about the importance of enrolling a broad age range and how that's being received by the clinical community from your perspective. Thanks.

另外，有件事讓我們印象深刻：我們做了一些 KOL 訪談，大家似乎——醫師社群似乎非常清楚你們的資料涵蓋很廣的年齡範圍。能否再多談談納入廣泛年齡層的重要性，以及從你們的角度，臨床社群對此的反應如何？謝謝。

Sure. So Chris, starting with the PPQ, we aligned on comparability when we had the clinical lot that was in Part A and then we ran our, call it, final commercial process, we ran a lot of that. And so it was one-to-one and the FDA deemed that that was analytically comparable. And what you have to continue to do as you produce more lots is demonstrate that there's -- those additional lots are also comparable.

當然。Chris，先從 PPQ 談起：當我們在 A 部分使用臨床批次時，我們就已就可比性（comparability）達成一致；接著我們執行了我們所稱的最終商業化製程，並以該製程生產了一個批次。因此是一對一的比較，而 FDA 認定在分析層面上是可比的。接下來你在生產更多批次時必須持續證明：這些新增批次同樣具可比性。

So at this last meeting, we shared with them multiple additional lots that we'd run, and they continued to say that we're comparable. Now, as you go into PPQ, you're generally doing two or three additional runs, and then you share that data with the FDA. So we're in the process of doing those runs right now. Assuming those runs continue to be demonstrating comparability, that's when you're able to pull the data.

所以在上一次會議中，我們向他們分享了我們額外跑過的多個批次，他們也持續表示我們是可比的。接著當你進入 PPQ 時，通常會再做兩到三次額外的生產，然後把那些資料分享給 FDA。所以我們目前正在進行這些生產。假設這些生產結果持續顯示可比性，那時你就能把資料彙整出來。

So the fact that we've been able to do it with multiple runs so far gives us a lot of confidence. There's a strong alignment with the FDA. And then we take that data package, and the next time we meet with them, we share that with them, and that's kind of the next step. So we feel like we're in a really good position on the CMC side, and we have them for quite some time. It is not on the critical path to the BLA submission.

因此，到目前為止我們已能在多次生產中做到這點，讓我們很有信心。我們與 FDA 之間有很強的一致性。接著我們會把那份資料套件帶去，下一次與他們會面時再分享，這就是下一步。所以我們覺得在 CMC 方面我們處於非常好的位置，而且我們已經與他們互動了一段時間。這並不在 BLA 申請提交的關鍵路徑上。

So that -- as it relates to the broad ages of enrollment, if you think about the prevalent population, 85% of the prevalent population is over the age of 10. So demonstrating effect across pediatric, adolescent, and adults is very, very important. Because as we've done market research with both caregivers and with clinicians, they plan on offering it across the age spectrum, and they're planning to offer it because there's demonstrated effect across the age spectrum.

至於廣泛年齡層的入組，如果你看現存（prevalent）病患族群，85% 的現存族群年齡在 10 歲以上。因此，證明在兒童、青少年與成人皆有療效是非常、非常重要的。因為我們對照護者與臨床醫師做市場研究後發現，他們計畫在整個年齡光譜提供這項治療，而他們之所以願意提供，是因為已證明在整個年齡光譜都有療效。

So we feel that we're in a good position to serve the broad community who's requesting gene therapy because of the data that we've generated. And that's why we're being thoughtful about making sure that there's representation across the age spectrum in Part B. So our whole goal is to make this available for all patients with Rett syndrome, and the data continue to support that. And I can tell you that the demand is high across the age groups based on what we've seen so far.

所以我們認為，基於我們產出的資料，我們處於一個很好的位置，能服務整個正在要求基因治療的廣大社群。這也是為什麼我們在 B 部分會審慎確保各年齡層都有代表性。我們的整體目標是讓所有雷特氏症（Rett syndrome）患者都能使用，而資料也持續支持這一點。而且我可以告訴你，根據我們目前看到的情況，各年齡層的需求都很高。

Great. Thank you.

很好。謝謝。

Thank you.

謝謝。

Jack Allen, Baird.

Jack Allen，Baird。

Hey. Congrats on the updates, and thanks for taking the questions. It sounds great to hear that enrollment is on track to be concluded in the second quarter of this year. I guess my question is pretty simple in that I was wondering if you'd provide any additional color surrounding how far you are as it relates to completing enrollment. How many patients have been dosed in the study? And then maybe if that's a little too direct, if you could just speak to the enthusiasm you're seeing from the patient community and the interest in the trial.

嗨。恭喜有新的進展，也謝謝讓我提問。聽到入組進度如期、預計在今年第二季完成，這很令人振奮。我想我的問題很簡單：想請你們再多提供一些關於入組完成度的細節，你們目前距離完成入組還有多遠？這項研究已經有多少位患者完成給藥？如果這樣問太直接，也請談談你們從病患社群看到的熱情程度，以及對試驗的興趣。

Yeah. I think Suku can take the second part of the question. I mean, we're not going to give specifics. I would just say the demand is super high. It's high across the age spectrum. Multiple sites, we've got 10 sites that are active. Multiple patients have been dosed across multiple sites. Most of the sites have multiple patients.

是的。我想 Suku 可以回答問題的第二部分。我的意思是，我們不會提供具體細節。我只能說需求非常高。在各個年齡層的需求都很高。多個試驗中心，我們有 10 個正在運作的中心。多個中心已對多名患者完成給藥。大多數中心都有多名患者。

So I mean, you want to talk a little bit about the enthusiasm and the demand that we're seeing across the spectrum?

所以我的意思是，你想稍微談談我們在各個族群看到的熱情與需求嗎？

Absolutely. So we have multiple Rett centers of excellence who are part of the clinical trial, and they all have 100, 200 plus patients. Many of the patients, caregivers, and parents have been very enthusiastic about being screened and enrolling in our trial.

當然。因此，我們有多個 Rett 卓越中心參與臨床試驗，而每個中心都有 100、200 名以上的患者。許多患者、照護者與家長都非常熱衷於接受篩檢並加入我們的試驗。

So I would say with confidence that we are over-enrolled and we have more than enough patients to dose to meet the 15 -- the number of 15 or a little bit more. So we should be -- we will be meeting our commitment to complete those things for both REVEAL Part B and ASPIRE by the end of the second quarter of this year.

所以我可以有信心地說，我們的入組人數超出預期，而且我們有綽綽有餘的患者可完成給藥，以達到 15 名——15 名這個數字或略多一些。因此，我們應該——我們將會在今年第二季末前，履行我們對 REVEAL B 部分與 ASPIRE 完成這些事項的承諾。

Great. Thanks so much for the color.

很好。非常感謝補充說明。

Thanks, Jack.

謝謝你，Jack。

Whitney Ijem, Canaccord Genuity.

Whitney Ijem，Canaccord Genuity。

Hey, guys. Thanks for taking the question. Just thinking about durability, how often are patients assessed in Part A? And I guess I'm just wondering if there's a scenario where later this year, either we or the FDA is getting like an 18-month update on those patients and then potential for longer-term updates going forward.

嗨，各位。謝謝讓我提問。我在想關於療效持久性（durability），A 部分患者多久評估一次？另外我想知道，是否可能在今年稍晚，我們或 FDA 會拿到這些患者的 18 個月更新資料，並且之後還可能持續有更長期的更新？

Thanks for that question, Whitney. That's actually a very important question that you raised.

謝謝這個問題，Whitney。你提出的其實是一個非常重要的問題。

So given that we have Part B ongoing and we have an agreement with the FDA that the six-month interim analysis once all 15 patients in Part B are dosed would be considered based on the efficacy and safety data for potential full approval of our product. The REVEAL Part A long-term data from a clinical standpoint, safety and efficacy, I think could significantly also impact the six-month interim analysis from Part B, collectively driving towards the full approval. And Sean clearly described that the FDA is aligned with us when it comes to the CMC process and the compatibility technicalities between the Part A product and the Part B product.

因此，鑑於我們的 B 部分正在進行中，且我們與 FDA 已達成共識：一旦 B 部分 15 名患者都完成給藥，將以 6 個月期中分析（interim analysis）的療效與安全性資料，作為我們產品可能獲得完全核准（full approval）的依據。從臨床角度來看，REVEAL A 部分的長期資料（安全性與療效）我認為也可能對 B 部分的 6 個月期中分析產生重大影響，兩者合併將共同推動走向完全核准。而 Sean 也清楚說明，FDA 在 CMC 流程以及 A 部分產品與 B 部分產品之間的相容性技術細節方面，與我們是一致的。

So to really answer your question on Part A, the long-term data, I think up to 18 months, being evaluated per the protocol post 12 months, every quarter, I think is going to be also important to the collective six-month interim analysis. And if the six-month interim analysis gives very useful clinical data, and Sean described the other scenario of Part B where you might need 12-month data as well, the REVEAL Part A persistence of effect long term will also, I think, influence further the confidence that our product will have immediate consistent and persistent effect long term as well in this patient community.

所以要真正回答你關於 A 部分的問題：長期資料我認為會一路到 18 個月；依照試驗計畫書，在 12 個月之後每一季評估一次，我認為這也會對整體的 6 個月期中分析很重要。而如果 6 個月期中分析提供非常有用的臨床資料，且 Sean 也描述了 B 部分另一種情境——可能也需要 12 個月資料——那麼 REVEAL A 部分長期的效果持續性（persistence of effect）我認為也會進一步影響我們的信心：我們的產品在這個患者族群中，能夠立即、穩定且長期持續地發揮效果。

Yeah. The only thing I would add, Whitney, is when we report the data, we will also report the data that's greater than 12 months. So you should have a real good sense of what's happening over time.

是的。Whitney，我唯一想補充的是，當我們公布資料時，也會一併公布超過 12 個月的資料。所以你會對隨時間推移的情況有非常清楚的掌握。

Got it. That's helpful. Thank you.

了解。這很有幫助。謝謝。

Thanks, Whitney.

謝謝你，Whitney。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO Capital Markets。

Hi. I'm Malcolm Hoffman on for Evan. Thanks for taking our question. Something about potential commercial manufacturing. I just wanted to ask what redundancies exist across TSHA-102 manufacturing chain that could help if there were any disruptions to the process? Thank you.

嗨。我是代替 Evan 的 Malcolm Hoffman。謝謝讓我們提問。想問一些關於未來商業化製造的問題。我想請教，在 TSHA-102 的製造鏈上有哪些備援機制，可以在流程出現任何中斷時提供協助？謝謝。

Yeah. So to answer the question, so we currently are at Catalent, and Catalent's Baltimore, Maryland, facility has obviously been infected, and they have extensive gene therapy manufacturing experience, and we feel really confident in the team that Catalent and our oversight of the team there. And importantly, as Sean mentioned earlier, we have ensured that, based on our lock manufacturing process, CMC is not on the critical path to a potential BLA submission.

好的。回答這個問題：我們目前在 Catalent；Catalent 位於馬里蘭州巴爾的摩的廠區顯然已經通過檢查（inspected），他們在基因治療製造方面有豐富經驗，我們對 Catalent 的團隊以及我們在那裡的監督都非常有信心。而且很重要的是，如 Sean 先前提到的，我們已確保基於我們已鎖定（lock）的製造流程，CMC 不會成為潛在 BLA 申請的關鍵路徑（critical path）。

And as it pertains to downstream potential redundancy in manufacturing, that's something as we get closer to Part B interim data readout, and as we get closer to a potential BLA submission, that's something we will evaluate to mitigate any potential disruption to supply chain. But we feel really confident given Catalent's manufacturing experience in that particular facility in Baltimore that that facility can meet our ultimate commercial demand.

至於製造端下游可能的備援，當我們更接近 B 部分期中數據揭露（readout），以及更接近潛在的 BLA 申請時，我們會評估這些事項，以降低供應鏈可能中斷的風險。但考量 Catalent 在巴爾的摩該廠區的製造經驗，我們非常有信心該廠能滿足我們最終的商業需求。

And that, Evan, that's where Sarepta is making elevators as well. And so it's been FDA inspected and they're very familiar, as Kamran said, with gene therapy commercial scale. So we feel very confident about that.

另外，Evan，那裡也是 Sarepta 進行製造的地方。因此該廠已接受 FDA 查核，他們也非常熟悉——如 Kamran 所說——基因治療的商業化規模生產。所以我們對此非常有信心。

Appreciate it. Thanks, guys.

了解，感謝。謝謝各位。

Thanks.

謝謝。

Yanan Zhu, Wells Fargo.

Yanan Zhu，Wells Fargo。

Hey. This is Jeff on for Yanan. Thanks for taking our question. Today and in the last couple of months, market research has been touched on, indicating strong demand for gene therapy in Rett and a clear preference for intrathecal delivery, including mentioning 80% of caregivers and clinicians are seeking gene therapy for their patients. Can you provide any additional color or details on this market research in terms of if you test any product profiles for TSHA-102 and patient physician preference specifically for TSHA-102?

嗨。我是代替 Yanan 的 Jeff。謝謝讓我們提問。今天以及過去幾個月，你們提到市場調研，指出 Rett 的基因治療需求強勁，且對鞘內（intrathecal）給藥有明確偏好；也提到有 80% 的照護者與臨床醫師正在為其患者尋求基因治療。能否就這項市場調研提供更多補充或細節，例如：你們是否針對 TSHA-102 測試任何產品特性描述（product profiles），以及患者與醫師對 TSHA-102 的偏好情況？

Yeah. I mean -- and there'll be more to come in the second half, deeper dives on the commercial aspect of things. But we essentially tested with physicians, so it was about half the physicians were at centers of excellence, half were not at centers of excellence. And then we also separately ran a study with caregivers of Rett patients or children with Rett across the age spectrum, and we kept it pretty simple.

是的。我的意思是——下半年我們會有更多內容，會在商業化層面做更深入的解析。但我們基本上是對醫師進行測試：大約一半的醫師來自卓越中心，另一半不在卓越中心。然後我們也另外針對 Rett 患者的照護者、或有 Rett 兒童的照護者做了一項研究，涵蓋各年齡層，而且我們把設計做得相當簡單。

We basically -- our product profile was our product profile that you've effectively seen, the responder rate, the CGI scores on average, with the duration of time that we've been testing these patients. Think about the last data update we gave last year and the deck that we used, it was effectively that on a one-pager. And then we just toddled that with, is it intrathecal or is it ICD, what would it matter, assuming the same set of data.

我們基本上——我們的產品特性描述就是你們實際上已經看過的那個：反應者比例（responder rate）、平均 CGI 分數，以及我們追蹤這些患者的時間長度。回想一下我們去年提供的最新數據更新以及所使用的簡報，那基本上就是把那些內容濃縮成一頁。然後我們再把它搭配一個問題：是鞘內給藥（intrathecal）還是 ICD？在假設資料相同的前提下，這會有什麼差別？

And so number one feedback consistently in both groups, physicians and the caregivers, was very high interest in gene therapy. They realized that you want something that treats the root cause. So there's a very high interest in seeking that out, number one. Number two, what was interesting is it's also -- there's high treatment being sought across the age groups, including those over 30. So that also is encouraging.

因此，第一個在兩個族群——醫師與照護者——中都一致出現的回饋，是對基因治療有非常高的興趣。他們理解你需要的是能治療根本原因的療法。所以，第一點是對尋求這類療法的興趣非常高。第二點，有趣的是，各年齡層都在積極尋求治療，包括 30 歲以上的患者。因此這也令人鼓舞。

And then when you distill this down, to make it real simple, and we didn't want to make it too technical at first. I think more has to be shown to get more precise on comparative product profiles. But if all things are equal on safety and efficacy, obviously there's a preference for the least invasive route, both in terms of perceived safety, but also just in terms of -- some of the physicians were making the point on throughput in the institutions that it's a lot easier to put -- let's just say you had a few other patients at an institution.

接著，當你把這些內容再提煉濃縮、把它講得很簡單時，我們一開始也不想講得太技術性。我認為要更精準地比較產品特徵（product profiles），還需要展示更多內容。但如果在安全性與療效上各方面都相同，顯然會偏好侵入性最低的給藥途徑；這不僅是就「感知上的安全性」而言，也包括——有些醫師也提到機構內的處置量（throughput）：要安排——就假設你在某個機構還有其他幾位病人。

It's easier to stage and manage those patients efficiently using intrathecally versus if you have to fight for OR time, neurosurgeon time, et cetera, it's harder to do that. You're going to have more intrusions, you're going to have more emergencies coming in that you're going to have to work to allocate time. So the scalability effect was something that was also quite top of mind for the physician group.

相較於必須去爭取手術室（OR）時間、神經外科醫師時間等等，採用鞘內給藥（intrathecally）更容易分期安排並有效率地管理這些病人。你會遇到更多插隊狀況，也會有更多急診病人進來，你必須想辦法分配時間。因此，可擴展性（scalability）的效果也是醫師群體非常關注的一點。

So hopefully, that gives you a little flavor for the data.

希望這能讓你對這些數據有一些感覺。

Yeah, got it. Thanks. Appreciate it.

好的，了解。謝謝。很感謝。

Sure.

不客氣。

Silvan Türkcan, Citizens.

Silvan Türkcan，Citizens。

Yeah, thank you so much for taking my question. I maybe just wanted to follow-up on the intrathecal injection here. So that is not a procedure, right? So that can be done in the outpatient setting versus maybe some other routes of administration that may potentially come to the market as well. Can you just speak about that and potentially the cost differential between a full procedure that would require OR time in neurosurgery versus not?

是的，非常感謝讓我提問。我想就鞘內注射（intrathecal injection）再追問一下。所以那不算是一個手術處置（procedure），對吧？因此可以在門診環境進行，相較之下，其他可能也會進入市場的給藥途徑可能就不一定。你能否談談這點，以及需要神經外科手術室（OR）時間的完整處置與不需要之間，成本差異可能有多大？

And then, I don't know if you can comment on this, but do you know the screen fail rate that you currently have? And is that predominantly because of the strictness around the baseline measures? Thank you.

另外，我不確定你是否能評論，但你知道目前的篩檢失敗率（screen fail rate）是多少嗎？而這主要是因為基線量測（baseline measures）的嚴格程度嗎？謝謝。

Yeah. In terms of the first question, what we're doing is a 20-minute lumbar puncture administration with mild or no sedation. So the patient can easily have this done and be out of the hospital well within -- yeah, same day, well within 24 hours. The ICD approach, obviously, you need to be in the OR for that. You have to have a neurosurgeon do the procedure, and so there is greater time and cost associated with that procedure.

是的。就第一個問題而言，我們做的是約 20 分鐘的腰椎穿刺給藥（lumbar puncture administration），只需輕度鎮靜或不需鎮靜。因此病人很容易完成，並可在——是的，同一天、且遠在 24 小時內就能出院。至於 ICD 的方式，顯然需要在手術室進行。你必須由神經外科醫師執行該處置，因此所需時間與成本都更高。

In terms of breaking it out, that's something we can talk more about in the second half. But just from an efficiency perspective, the ability to give someone a lumbar puncture, obviously, you can do that in various spots throughout the hospital and do it safely. That's not the case with ICD. I mean, there's certain parameters that you're going to have to have, certain staff that you're going to have to have, including neurosurgeons to do the procedure itself.

至於要如何拆分細項，我們可以在後半段再多談。但就效率角度來看，能夠替病人做腰椎穿刺，顯然你可以在醫院內不同地點安全地進行。ICD 則不是這樣。我的意思是，你會需要符合某些條件、需要特定人力配置，包括神經外科醫師來執行處置本身。

And keep in mind that the OR time is booked in advance. There's only so much OR space. There's only very few neurosurgeons to do these procedures. So my point is that, and the point that the physicians were making, if you have a large number of patients, it would be much more efficient in the institution to be able to dose them via the intrathecal route for the reasons that I gave.

而且請記住，手術室（OR）時間是事先排程的。手術室空間有限。能做這些處置的神經外科醫師也非常少。所以我的重點是——也是醫師們提出的重點——如果你有大量病人，基於我剛才說的原因，機構內以鞘內途徑給藥會有效率得多。

The second question, I didn't quite get. So I don't know if anyone on the table got that. Or Silvan, if you could repeat that, I didn't get it.

第二個問題我沒有完全聽清楚。所以我不確定在座是否有人聽到了。或者 Silvan，你能再重複一次嗎？我沒聽清楚。

Yeah. And obviously, trials are ongoing, but if you could just speak to the current screen fail rate, just to give a feel of is there a significant patient population out there that just cannot qualify for this therapy because, let's say, they're too advanced or not advanced enough. Or do you have any data points in that direction? Thank you.

好的。而且顯然試驗仍在進行中，但如果你能談談目前的篩檢失敗率（screen fail rate），讓大家感受一下：是否有相當比例的病人族群因為例如病程太晚期或不夠晚期，而無法符合這項治療的資格。或你是否有任何相關數據點？謝謝。

So Silvan, you asked actually a very interesting and important question, because remember, Rett syndrome, there are multiple different genotypes. There is a very differentiated phenotypic presentation, meaning multiple phenotypes that present as Rett syndrome, and then you also have the complexity of mosaicism when it comes to central nervous system. So it's a unique combination that eventually results in a complex clinical presentation.

Silvan，你其實問了一個非常有趣且重要的問題。因為請記得，雷特氏症（Rett syndrome）有多種不同的基因型（genotypes）。其表型呈現（phenotypic presentation）也非常分化，也就是說，有多種表型會以雷特氏症的樣貌呈現；此外，中樞神經系統還存在鑲嵌現象（mosaicism）的複雜性。因此，這是一種獨特的組合，最終會導致複雜的臨床表現。

And what we've shown in REVEAL Part A is that regardless of genotype or phenotypic presentation or age, our gene therapy given through a simple lumbar puncture consistently provides superior clinical efficacy with no major safety concerns at this point in time.

而我們在 REVEAL A 部分所展示的是：不論基因型、表型呈現或年齡，我們透過簡單腰椎穿刺給予的基因治療，都能一致地提供更佳的臨床療效，且截至目前沒有重大安全性疑慮。

When it comes to screen failure rates, in Part A, as far as I recall, there were no screen failures. In Part B, we have not discussed the screen failures publicly at this point in time, but they are minimal. And given that the common route to the disease is a lack of MECP2 or minimal MECP2 levels that have clinical efficacy or impact on the patient, restoration of MECP2 levels using TSHA-102 in general addresses the lack of MECP2 and has superior clinical efficacy results up to now.

至於篩檢失敗率，在 A 部分，就我記得是沒有篩檢失敗。在 B 部分，我們目前尚未公開討論篩檢失敗的情況，但比例很低。而且由於此疾病的共同路徑是缺乏 MECP2 或 MECP2 水平極低、以致對病人產生臨床療效或影響；因此，使用 TSHA-102 來恢復 MECP2 水平，整體而言可針對 MECP2 缺乏的問題，並且截至目前呈現更優異的臨床療效結果。

So my assumption here is as we experience and complete Part B REVEAL study and ASPIRE, that screen failure or loss of the market, I guess, or clinical market access to a large group of patients is not an issue and will not be an issue. I hope that answers your question.

因此我的推測是，隨著我們推進並完成 REVEAL 研究的 B 部分以及 ASPIRE，篩檢失敗——或我想你指的是市場流失、也就是臨床市場可及性無法涵蓋一大群病人——不會是問題，也不會成為問題。希望這回答了你的問題。

Yeah, great. Very helpful. Thank you.

好的，很棒。非常有幫助。謝謝。

Thanks, Silvan.

謝謝你，Silvan。

This does conclude our question-and-answer session. I would now like to turn it back to Sean Nolan, Chairman and CEO.

我們的問答環節到此結束。接下來我想把時間交回給董事長兼執行長 Sean Nolan。

Thanks to everyone who called in. I really appreciate the time and interest in Taysha. Have a great day.

感謝所有來電參與的各位。我非常感謝大家對 Taysha 的時間與關注。祝各位有美好的一天。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝您參與今天的電話會議。本次議程到此結束。您現在可以掛線。