Taysha Gene Therapies Inc (TSHA) 2025 Q2 法說會逐字稿

Ladies and gentlemen, good morning, and welcome to Taysha Gene Therapies second quarter 2025 earnings conference call. (Operator Instructions) As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Hayleigh Collins, Director, Head of Corporate Communications. Please go ahead.

女士們，先生們，早安，歡迎參加 Taysha Gene Therapies 2025 年第二季財報電話會議。（操作員指示）提醒一下，本次會議正在錄音。現在我很高興向大家介紹主持人、企業傳播總監兼主管 Hayleigh Collins。請繼續。

Thank you. Good morning, and welcome to our second quarter 2025 financial results and corporate update conference call. Earlier today, Taysha issued a press release announcing financial results for the second quarter ended June 30, 2025. A copy of this press release is available on the company’s website and through our SEC filings.

謝謝。早安，歡迎參加我們 2025 年第二季財務業績和公司更新電話會議。今天早些時候，Taysha 發布了一份新聞稿，宣布了截至 2025 年 6 月 30 日的第二季財務表現。本新聞稿的副本可在公司網站和美國證券交易委員會 (SEC) 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; Kamran Alam, Chief Financial Officer and Dr. Elsa Rossignol, Director of the Integrated Rett Syndrome Clinic at Sainte-Justine in Montreal and Principal Investigator of the VEAL Phase 1/2 trials.

參加今天電話會議的還有 Taysha 執行長 Sean Nolan、總裁兼研發主管 Sukumar Nagendran、財務長 Kamran Alam 和蒙特利爾 Sainte-Justine 綜合 Rett 綜合徵診所主任兼 VEAL 1/2 期試驗首席研究員 Elsa Rossignol 博士。

We will be presenting slides to accompany our prepared remarks today, which will be available on our website after the call. We will host a question and answer session following our prepared remarks. Please note that Dr. Rossignol will be available to take questions until 09:20 AM Eastern Time, after which she will be stepping away for her clinic commitments.

我們將在今天的準備好的演講中提供幻燈片，這些幻燈片將在電話會議結束後在我們的網站上提供。我們將在準備好的發言之後舉辦問答環節。請注意，Rossignol 博士將在東部時間上午 09:20 之前回答問題，之後她將離開診所處理事務。

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 and to our other product candidates to positively impact quality of life and also 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 and making regulatory submissions.

在今天的電話會議上，我們將做出前瞻性陳述，包括有關 TSHA-102 潛力的陳述，包括在臨床試驗中迄今為止接受治療的患者中最初看到的任何有利結果的可重複性和持久性，包括關於功能里程碑和我們的其他候選產品對我們尋求治療的患者的生活質量和疾病進程產生積極影響的陳述，我們對候選產品的研究開發和監管計劃報告

Timing or outcomes of communications with the FDA and Health Canada on the regulatory pathway for TSHA-102, the potential for product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies and the market opportunity for our programs.

與 FDA 和加拿大衛生部就 TSHA-102 的監管途徑進行溝通的時間或結果、候選產品獲得 FDA 或同等外國監管機構監管批准的可能性以及我們項目的市場機會。

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.

本次電話會議還可能包含與 Taysha 的成長、預測現金流和未來營運績效、產品候選的發現和開發、策略聯盟和智慧財產權有關的前瞻性陳述，以及非歷史事實或資訊的事項。各種風險可能導致 Taysha 的實際結果與此類前瞻性陳述中明示或暗示的結果有重大差異。

For a list and description of the risks and uncertainties we face, please see the reports we filed with the SEC, including in our annual report on Form 10-K for the full year ended December 31, 2024, that we filed February 26, 2025. And our quarterly report on Form 10-Q for the quarter ended June 30, 2025, we filed today.

有關我們面臨的風險和不確定性的清單和說明，請參閱我們向美國證券交易委員會提交的報告，包括我們於 2025 年 2 月 26 日提交的截至 2024 年 12 月 31 日的全年 10-K 表年度報告。我們今天提交了截至 2025 年 6 月 30 日的 10-Q 表格季度報告。

This conference call contains time sensitive information that’s accurate only as of the date of this live broadcast, August 12, 2025. Taysha undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances after the date of this call, except as may be required by applicable securities laws.

本次電話會議包含時間敏感訊息，其準確性僅限於本次直播之日（2025 年 8 月 12 日）。Taysha 不承擔修改或更新任何前瞻性陳述以反映本次電話會議日期之後的事件或情況的義務，除非適用的證券法另有要求。

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

現在，我想將電話轉給我們的執行長 Sean Nolan。

Thank you, Hayleigh, and welcome everyone to our second quarter conference call. I will begin with an update on our recent activities and regulatory progress for our lead TSHA-102 Rett syndrome program, including new details of our FDA aligned pivotal trial design and our registrational pathway.

謝謝你，Hayleigh，歡迎大家參加我們的第二季電話會議。我將首先介紹我們領先的 TSHA-102 雷特氏症計畫的最新活動和監管進展，包括我們與 FDA 一致的關鍵試驗設計和註冊途徑的新細節。

Next, Suku will discuss our natural history data analysis which underpins our REVEAL pivotal trial design. I’ve invited Dr. Elsa Rossignol, Director of the Integrated Rett Syndrome Clinic at Sainte-Justine in Montreal and a Principal Investigator of the REVEAL trials. To present the previously disclosed Part A clinical data from our REVEAL Phase 1/2 trials that she presented at the International Rett Syndrome Foundation Scientific Meeting in June.

接下來，Suku 將討論我們的自然史資料分析，這是我們 REVEAL 關鍵試驗設計的基礎。我邀請了蒙特婁聖賈斯汀綜合雷特氏症診所主任兼 REVEAL 試驗首席研究員 Elsa Rossignol 博士。展示她於 6 月在國際雷特症候群基金會科學會議上展示的我們 REVEAL 1/2 期試驗先前揭露的 A 部分臨床數據。

Those who attended may recall how impactful her presentation was to the audience. Today, we’re excited to expand its reach to the broader community as these data have been central to our clinical discussions with regulators in preparation for our pivotal trial.

參加者可能還記得她的演講給觀眾留下了多麼深刻的印象。今天，我們很高興將其影響力擴大到更廣泛的社區，因為這些數據對於我們與監管機構進行臨床討論以準備關鍵試驗至關重要。

Cameron will then follow-up with a financial update and I will provide closing remarks before opening the call to questions. We have continued to make strong progress supporting the advancement of our TSHA-102 program.

卡梅倫隨後將報告財務最新情況，我將在開始提問之前致最後總結。我們在支持 TSHA-102 計劃的推進方面繼續取得了重大進展。

This included obtaining alignment with the FDA and Health Canada to proceed with initiating our REVEAL pivotal trial, reporting positive clinical data supporting the therapeutic potential of TSHA-102 and strengthening our balance sheet. We believe this meaningful progress sets us on a clear and efficient path towards the potential registration of TSHA-102.

這包括與 FDA 和加拿大衛生部達成一致，繼續啟動我們的 REVEAL 關鍵試驗，報告支持 TSHA-102 治療潛力的積極臨床數據並加強我們的資產負債表。我們相信，這一有意義的進展將為我們在 TSHA-102 的潛在註冊方面走上一條清晰而有效的道路。

In May, we announced that we had reached alignment with FDA on key design elements of our REVEAL pivotal trial and next steps for enabling study initiation. Subsequently, we submitted our IND application amendment to the FDA and CTA amendment to Health Canada. I am now pleased to report that we have officially commenced site activation for our REVEAL pivotal trial.

5 月份，我們宣布已與 FDA 就 REVEAL 關鍵試驗的關鍵設計要素以及啟動研究的後續步驟達成協議。隨後，我們向 FDA 提交了 IND 申請修正案，並向加拿大衛生部提交了 CTA 修正案。我現在很高興地報告，我們已經正式開始 REVEAL 關鍵試驗的現場活化。

In accordance with the key design elements we previously aligned on with FDA following receipt of no objection letter from Health Canada and feedback from the FDA. As a result of this progress, we anticipate beginning patient enrollment for our pivotal trial in the fourth quarter of this year.

根據我們先前與 FDA 達成一致的關鍵設計要素，在收到加拿大衛生部的無異議函和 FDA 的回饋後。由於這項進展，我們預計今年第四季開始招募關鍵試驗的患者。

Our frequent and constructive dialogue with the FDA through the RMAT mechanism has been instrumental in enabling us to navigate this novel regulatory pathway, which I will discuss in more detail shortly. Rett syndrome is a rare progressive and debilitating neurodevelopmental disease affecting an estimated 15,000 to 20,000 patients across the US, Europe and UK. It often necessitates 24/7 care and lifelong support.

我們透過 RMAT 機制與 FDA 進行頻繁且建設性的對話，這對我們駕馭這一新的監管途徑起到了重要作用，我將在稍後對此進行更詳細的討論。雷特氏症是一種罕見的進行性、使人衰弱的神經發育疾病，影響著美國、歐洲和英國約 15,000 至 20,000 名患者。它通常需要全天候護理和終身支援。

Despite the severity, there are no currently approved therapies that treat the underlying genetic root cause of this disease, underscoring the urgency for new therapeutic advancements. TSHA-102 is highly differentiated gene therapy candidate designed to target the genetic root cause of Rett syndrome.

儘管病情嚴重，但目前尚無核准的療法可以治療疾病的潛在遺傳根源，凸顯了新療法進展的迫切性。TSHA-102 是一種高度差異化的基因治療候選藥物，旨在針對雷特症候群的遺傳根源。

With key attributes that intend to support safety and potential commercial viability, we believe TSHA-102 is poised to redefine the treatment landscape for Rett syndrome. Specifically, it leverages the clinically and commercially proven AAV9 vector, which is a well characterized safety profile that’s been demonstrated in studies for other third party gene therapies across multiple indications.

憑藉旨在支持安全性和潛在商業可行性的關鍵屬性，我們相信 TSHA-102 將重新定義 Rett 症候群的治療前景。具體來說，它利用了經過臨床和商業驗證的 AAV9 載體，該載體具有良好的安全性，已在其他第三方基因療法針對多種適應症的研究中得到證實。

Another important distinction is that TSHA-102 is administered via lumbar intrathecal injection, which is a routine minimally invasive delivery approach. Commercially, this can be advantageous in that it does not require a surgical suite or neurosurgery expert delivery and it can be performed as a routine outpatient procedure.

另一個重要的區別是，TSHA-102 是透過腰椎鞘內注射給藥的，這是一種常規的微創給藥方法。從商業角度來看，這是有利的，因為它不需要手術室或神經外科專家的幫助，並且可以作為常規門診手術進行。

Additionally, intrathecal administration delivers the vector directly to the cerebrospinal fluid, which facilitates widespread biodistribution and transduction within the CNS, while limiting systemic circulation. This reduces peripheral tissue exposure that may help lower the risk of off target effects, including immune responses and systemic toxicities, thereby potentially contributing to a more favorable safety profile.

此外，鞘內給藥可將載體直接輸送到腦脊髓液，從而促進中樞神經系統內的廣泛生物分佈和轉導，同時限制全身循環。這減少了周邊組織暴露，可能有助於降低脫靶效應的風險，包括免疫反應和全身毒性，這可能有助於提高安全性。

From the outset, our clinical development strategy has been deeply data driven with a focus on defining the most objective, clinically meaningful way to assess TSHA-102 across a broad patient population. Our robust analysis of the Rett syndrome natural history dataset demonstrated that after the age of six years, the likelihood of achieving defined developmental milestones across the core functional domains of Rett syndrome is approximately 0%.

從一開始，我們的臨床開發策略就深深地以數據為驅動，重點是確定最客觀、最具臨床意義的方法來評估廣大患者群體中的 TSHA-102。我們對 Rett 症候群自然史資料集的穩健分析表明，六歲以後，實現 Rett 症候群核心功能領域定義的發育里程碑的可能性約為 0%。

This established the developmental plateau population. These important findings underpin our FDA aligned pivotal trial design and allow us to objectively measure the functional aspects of TSHA-102 on essential activities of daily living.

這確立了人口發展的平台期。這些重要發現鞏固了我們符合 FDA 要求的關鍵試驗設計，並使我們能夠客觀地衡量 TSHA-102 對日常生活基本活動的功能面。

As I mentioned, we are pleased to have commenced site activation for our REVEAL pivotal trial, which will assess the percentage of patients in the developmental plateau population who gain or regain one or more developed milestones as part of the primary endpoint with each patient serving as their own control.

正如我所提到的，我們很高興已經開始為我們的 REVEAL 關鍵試驗啟動現場，該試驗將評估發育平台期人群中獲得或重新獲得一個或多個已發展里程碑的患者的百分比作為主要終點的一部分，每個患者都作為自己的對照。

Based on the Part A data from our REVEAL 1.2 trials, it’s encouraging that all 10 patients treated with TSHA-102 gained or regained one or more developmental milestones corresponding to a 100% response rate for the pivotal trial primary endpoint based on the May 25 data cut off.

根據我們 REVEAL 1.2 試驗的 A 部分數據，令人鼓舞的是，所有 10 名接受 TSHA-102 治療的患者均獲得或重新獲得了一個或多個發育里程碑，根據 5 月 25 日的數據截止，這相當於關鍵試驗主要終點的 100% 的反應率。

With safety at the forefront, we are pleased to share the low and high dose of TSHA-102 continue to be generally well tolerated with no treatment related serious adverse events or dose limiting toxicities in the 12 patients treated as of August 2025 data cut off.

以安全為首要考慮，我們很高興地分享，截至 2025 年 8 月數據截止，接受治療的 12 名患者中，低劑量和高劑量的 TSHA-102 仍然普遍耐受性良好，沒有出現與治療相關的嚴重不良事件或劑量限制毒性。

Lastly, we recently completed a public follow on offering that resulted in total gross proceeds of $230 million including full exercise of the underwriters option to purchase additional shares, extending our cash runway into 2028.

最後，我們最近完成了公開後續發行，總收益為 2.3 億美元，其中包括承銷商充分行使購買額外股份的選擇權，將我們的現金流量延長至 2028 年。

With our balance sheet strengthened, our pivotal trial underway and a defined path to registration, we believe we are well positioned to advance TSHA-102 to benefit patients living with this devastating disease. Our REVEAL clinical development program was designed to support the future approval of TSHA-102 for the treatment of females aged two years and older with Rett syndrome. Recall Part A was our dose escalation phase where we treated 12 patients aged 6 years to 21 years.

隨著我們資產負債表的加強、關鍵試驗的進行以及註冊路徑的明確，我們相信我們已做好準備，推進 TSHA-102 的發展，造福患有這種毀滅性疾病的患者。我們的 REVEAL 臨床開發計劃旨在支持未來批准 TSHA-102 用於治療兩歲及以上患有 Rett 綜合徵的女性。回想一下，A 部分是我們的劑量遞增階段，我們治療了 12 名年齡在 6 歲至 21 歲之間的患者。

In our two Phase 1/2 REVEAL trials with one of the two dose levels. The totality of the Part A data help inform our discussions with the FDA and Health Canada on the optimal trial design for Part B, the pivotal phase of our trials.

在我們的兩項 1/2 期 REVEAL 試驗中，採用了兩種劑量等級之一。A 部分的全部數據有助於我們與 FDA 和加拿大衛生部討論 B 部分（試驗的關鍵階段）的最佳試驗設計。

Our REVEAL pivotal Part B trial will evaluate developmental milestone gain and regain in the developmental plateau population. In parallel, we previously announced we are aligned with the FDA on an extrapolation approach in a separate safety focused study evaluating TSHA-102 in the pre developmental plateau population of females aged 2 to less than 6 years. Given the high incidence of spontaneous milestone gains in this population, safety will be the primary focus and efficacy will be extrapolated from the developmental plateau population.

我們的 REVEAL 關鍵 B 部分試驗將評估發育平台期人群的發育里程碑增益和恢復。同時，我們先前宣布，我們將與 FDA 就外推法進行一項單獨的安全重點研究，評估 TSHA-102 在 2 歲至 6 歲以下女性發育前平台期人群中的作用。鑑於該族群中自發性里程碑式成長的發生率很高，安全性將成為主要關注點，並且療效將從發育平台期人群中推斷出來。

Importantly, we believe this two study approach allows us to generate safety and efficacy data across the broad Rett syndrome population, while mitigating disease heterogeneity risk. Leveraging a pivotal trial design focused on targeted enrollment of patients within the developmental plateau population provides high statistical confidence given the approximately 0% likelihood of spontaneous milestone achievement in this population.

重要的是，我們相信這兩種研究方法使我們能夠在廣泛的 Rett 綜合徵人群中產生安全性和有效性數據，同時降低疾病異質性風險。利用專注於在發育平台期人群中定向招募患者的關鍵試驗設計，可提供較高的統計信心，因為該人群自發實現里程碑的可能性約為 0%。

From a CMC perspective, the pivotal TSHA-102 product has been released and cleared for use in our REVEAL pivotal trial. As previously disclosed, the FDA approved the use of the pivotal lot, which is manufactured from the planned commercial manufacturing process and agreed that it was comparable with the clinical material used in Part A. This achievement supports product consistency and quality, which are essential pillars of safety.

從 CMC 角度來看，關鍵的 TSHA-102 產品已經發布並獲準用於我們的 REVEAL 關鍵試驗。如前所述，FDA 批准使用關鍵批次，該批次採用計劃的商業化生產流程生產，並同意其與 A 部分使用的臨床材料相當。這項成就支持了產品的一致性和質量，而這是安全的重要支柱。

Furthermore, the streamlines are passed to initiating the pivotal trial and underscores our CMC readiness to support a future BLA submission. Our REVEAL pivotal trial for TSHA-102 will reflect a single arm open label pivotal trial design with each patient serving as their own control. The high dose of TSHA-102 of 1e to the 15 total vector genomes will be evaluated and we will enroll 15 females between the ages of 6 years and less than 22 years in the developmental plateau population.

此外，這些流程已傳遞至啟動關鍵試驗，並強調了我們的 CMC 已準備好支援未來的 BLA 提交。我們針對 TSHA-102 的 REVEAL 關鍵試驗將反映單臂開放標籤關鍵試驗設計，每位患者都作為自己的對照組。我們將對 1e 至 15 個總載體基因組的高劑量 TSHA-102 進行評估，並將在發育平台期人群中招募 15 名年齡在 6 歲至 22 歲以下的女性。

As mentioned, the primary endpoint will assess the percentage of patients who gain or regain one or more developmental milestones from the list of 28 milestones across the core functional domains of communication, fine motor and gross motor.

如上所述，主要終點將評估在溝通、精細運動和粗大運動等核心功能領域的 28 個里程碑中獲得或重新獲得一個或多個發展里程碑的患者百分比。

Importantly, this responder definition was supported by the FDA and Health Canada as part of our recent feedback. With this established, we continue to believe Part A of our REVEAL trial supports the pivotal trial as well powered to establish efficacy.

重要的是，作為我們最近的回饋的一部分，該響應者定義得到了 FDA 和加拿大衛生部的支持。有了這一點的確立，我們仍然相信 REVEAL 試驗的 A 部分支持關鍵試驗，並且能夠確定療效。

We plan to conduct a 6 month interim analysis in addition to a 12 month primary analysis, which could potentially expedite BLA submission by two quarters to three quarters. Key secondary endpoints include the average number of total developmental milestones gained or regained per patient following TSHA-102 as well as clinician assessed outcomes including the rMVA and the CGII.

我們計劃在 12 個月的初步分析之外進行 6 個月的中期分析，這可能會將 BLA 提交速度加快兩個季度到三個季度。關鍵次要終點包括 TSHA-102 後每位患者獲得或恢復的平均總發育里程碑數以及臨床醫生評估的結果（包括 rMVA 和 CGI​​）。

These secondary endpoints are designed to capture the broad therapeutic outcomes across the domains of communication, fine motor, gross motor and autonomic function that are central to the burden of disease. We are focused on site activation, which we anticipate will enable us to begin patient enrollment in the fourth quarter of this year.

這些次要終點旨在捕捉對疾病負擔至關重要的溝通、精細運動、粗大運動和自主神經功能等領域的廣泛治療結果。我們專注於站點激活，預計這將使我們能夠在今年第四季度開始招募患者。

Importantly, our pivotal trial primary endpoint is an objective, clinically meaningful and individualized assessment of function in the developmental plateau population. It was supported by caregiver research and natural history and has been aligned on with the FDA.

重要的是，我們關鍵試驗的主要終點是對發育平台期人群的功能進行客觀、具有臨床意義和個性化的評估。它得到了護理人員研究和自然歷史的支持，並與 FDA 保持一致。

As such, we believe achievement of this endpoint has the potential to redefine expectations and expand the possibilities of gene therapy for patients with Rett syndrome. With the pivotal trial now underway, it is important to understand the data driven approach we took to define this novel regulatory pathway, which was informed by the natural history and our REVEAL Part A clinical data. I will now turn the call over to Suku to discuss this.

因此，我們相信實現這一終點有可能重新定義期望並擴大雷特氏症患者基因治療的可能性。隨著關鍵試驗的進行，了解我們用來定義這一新監管途徑的數據驅動方法非常重要，該方法基於自然歷史和我們的 REVEAL Part A 臨床數據。我現在將電話轉給 Suku 來討論此事。

Suku?

蘇庫？

Thank you, Sean. The longitudinal NIH funded IRSF natural history study data represents the largest global Rett syndrome natural history data set in which patients were assessed by direct examination. This included longitudinal data on the gain, loss and regain of developmental milestones in the co-functional domains of Rett syndrome. These data were collected via clinician conducted interviews with primary caregivers at 6 month to 12 month intervals.

謝謝你，肖恩。由 NIH 資助的縱向 IRSF 自然史研究數據代表了全球最大的 Rett 綜合徵自然史數據集，其中患者通過直接檢查進行評估。這包括雷特氏症共同功能領域中發展里程碑的獲得、喪失和恢復的縱向資料。這些數據是透過臨床醫生每隔 6 個月至 12 個月對主要照顧者進行的訪談收集的。

We selected a large cohort of approximately 1,100 females with up to 14 years of follow-up who closely aligned with our REVEAL trial enrollment criteria. We used this data to build age and time based cumulative incidence curves, which demonstrate the likelihood of gaining a new milestone based on age and the likelihood of regaining a milestone that was lost based on time since loss.

我們選擇了大約 1,100 名女性組成的大型群體，並進行了長達 14 年的隨訪，這些女性與我們的 REVEAL 試驗入選標準非常吻合。我們利用這些數據建立了基於年齡和時間的累積發生率曲線，該曲線展示了基於年齡獲得新里程碑的可能性，以及基於失去時間重新獲得失去的里程碑的可能性。

These models showed clear age and time based trends in developmental milestone acquisition that have strengthened the field understanding of longitudinal disease progression, substantiated the disease modifying potential of TSHA-102 and informed our discussions with the FDA on our proposed pivotal trial design. As seen on the slide, we built a tool that predicts the likelihood of a developmental milestone gain based on age and regain based on time since loss.

這些模型顯示了發展里程碑獲取中基於年齡和時間的明顯趨勢，這加強了對縱向疾病進展的現場理解，證實了 TSHA-102 的疾病修飾潛力，並為我們與 FDA 就我們提出的關鍵試驗設計的討論提供了資訊。如幻燈片所示，我們建立了一個工具，可以根據年齡預測發育里程碑增益的可能性，並根據損失後的時間來預測恢復的可能性。

Importantly, these incidence models demonstrated that the likelihood of gaining or regaining any of the 28 defined developmental milestones for our primary endpoint is highly predictable in patients 6 years of age or older. Here you will see three examples of milestone gains across the three core domains, demonstrating that when an untreated patient achieved these milestones, it occurred before the age of 6. After the age of 6, the curve flattens with approximately 0% likelihood of an individual gaining these milestones.

重要的是，這些發病率模型表明，對於 6 歲或以上的患者來說，獲得或重新獲得我們主要終點的 28 個定義的發展里程碑中的任何一個的可能性都是高度可預測的。在這裡，您將看到三個核心領域里程碑式進步的三個例子，表明未經治療的患者在 6 歲之前就實現了這些里程碑。6 歲以後，曲線趨於平緩，個人實現這些里程碑的可能性約為 0%。

We leverage these findings to establish the developmental plateau population, which is the population of age 6 years and older, at which the likelihood of milestone gain and regain becomes predictable. And as mentioned, this is the co-population we are enrolling in our pivotal trial.

我們利用這些發現來確定發育平台期人群，即 6 歲及以上的人群，在此年齡段，里程碑式增長和恢復的可能性變得可預測。正如所提到的，這是我們在關鍵試驗中招募的共同人群。

This slide highlights the 28 developmental milestones selected for inclusion in our primary endpoint, each meeting predefined criteria that is they are meaningful to caregivers, represent activities of daily living and demonstrated between 0% and less than 6% likelihood of spontaneous achievement in untreated individuals aged 6 years and older.

這張投影片重點介紹了我們選定的納入主要終點的 28 個發展里程碑，每個里程碑都符合預先定義的標準，即對護理人員有意義、代表日常生活活動，並且未經治療的 6 歲及以上個體自發實現的可能性在 0% 到 6% 以下。

This illustrative graphic helps put these findings into context. Our natural history analysis uncovered the developmental plateau population of patients aged 6 years and older, where there’s an exceedingly low chance of two things: number one, gaining new developmental milestones and number two, regaining developmental milestones that were lost after a defined number of years.

這張說明性圖表有助於理解這些發現的背景。我們的自然史分析發現了 6 歲及以上患者的發育平台期人群，其中發生兩件事的可能性極低：第一，獲得新的發育里程碑；第二，重新獲得在一定年限後失去的發育里程碑。

Therefore, the gain of new or restoration of previously lost milestones presents an objective clinically meaningful and data driven way to assess the efficacy of TSHA-102 in a broad population. We applied a rigorous evaluation criteria to our Part A developmental milestone data to enable a reliable, objective and consistent assessment of TSHA-102's efficacy.

因此，獲得新的里程碑或恢復先前失去的里程碑提供了一種客觀的、具有臨床意義的、數據驅動的方法來評估 TSHA-102 在廣泛人群中的療效。我們對 A 部分發展里程碑資料應用了嚴格的評估標準，以便對 TSHA-102 的功效進行可靠、客觀和一致的評估。

As a first in human study, we evaluated a range of clinical outcome assessments in Part A to generate a robust data set to inform our pivotal trial design. As such, select developmental milestones were captured through video recorded evaluations, clinical outcome assessments, caregiver assessments and clinician notes. We applied structured evaluation criteria to the available video evidence milestones.

作為首次人體研究，我們評估了 A 部分中的一系列臨床結果評估，以產生可靠的數據集來為我們的關鍵試驗設計提供資訊。因此，透過視訊記錄評估、臨床結果評估、護理人員評估和臨床醫生記錄來捕捉選定的發展里程碑。我們對可用的視訊證據里程碑應用了結構化評估標準。

To qualify as a milestone achievement following TSHA-102, there were three criteria that had to be met. First, the milestone had either never been gained or was lost sufficiently long ago such that the likelihood of spontaneous gain regain was less than 6.7% based on reviews of patients’ medical history and available baseline video data.

要成為 TSHA-102 之後的里程碑成就，必須滿足三個標準。首先，根據對患者病史和可用基線視訊資料的回顧，這一里程碑要么從未實現，要么很久以前就丟失了，因此自發性恢復的可能性低於 6.7%。

Second, there had to be video documentation of the milestone achievement post TSHA-102 treatment. Third, this video evidence was independently evaluated by multiple external central raters who use pre specified definitions of achievement for each of the 28 milestones based on the pivotal trial protocol to determine whether a milestone was demonstrated.

其次，必須有 TSHA-102 治療後里程碑式成就的錄影記錄。第三，該影片證據由多名外部中央評估員獨立評估，他們根據關鍵試驗方案，使用預先指定的 28 個里程碑成就定義來確定是否實現了里程碑。

By leveraging this criteria, we believe the Part A of our REVEAL trials is a reliable reflection of TSHA-102's impact on developmental milestone achievement well beyond what’s statistically probable for these patients and importantly that our pivotal trial is well powered to establish the therapeutic impact of TSHA-102.

透過利用這一標準，我們相信 REVEAL 試驗的 A 部分可靠地反映了 TSHA-102 對發育里程碑成就的影響，遠遠超出了這些患者在統計上可能達到的範圍，而且重要的是，我們的關鍵試驗完全有能力確定 TSHA-102 的治療效果。

Beyond the video evidence milestone data, we collected data that further demonstrate developmental milestone achievement and functional improvements in activities of daily living across the core domains of the disease, which we look forward to sharing in the fourth quarter of this year to further support the broad therapeutic impact.

除了視訊證據里程碑數據之外，我們還收集了進一步證明疾病核心領域的發展里程碑成就和日常生活活動功能改善的數據，我們期待在今年第四季度分享這些數據，以進一步支持廣泛的治療影響。

With that, I’m pleased to turn the call over to Dr. Elsa Rossignol to present the previously disclosed Part A data. Elsa?

有了這些，我很高興將電話轉給 Elsa Rossignol 博士，讓她介紹先前披露的 A 部分數據。艾莎？

Thank you. So it’s a pleasure to be here and to describe what we’ve, as Suku said, already presented in the IRFS meeting in June. And so next slide, please. Okay. So as we’re moving on, we’ve observed, as Suku was mentioning -- I’m sorry. Do you hear me? Can you move the slide? Are you guys hearing me?

謝謝。因此，我們很高興來到這裡並介紹我們在 6 月 IRFS 會議上已經提出的內容，正如 Suku 所說。請翻到下一張投影片。好的。因此，隨著我們繼續前進，我們觀察到，正如 Suku 所提到的——我很抱歉。你聽見我說話了嗎？你能移動幻燈片嗎？你們聽到我說話了嗎？

Yeah, we can hear you.

是的，我們能聽到你的聲音。

Okay. Very good. So please move the slides. Thank you. Alright, so as Suku was mentioning, the data from Part A was reanalyzed using independent central raters to assess gains or regains of any developmental milestones that were part of these 28 milestones isolated based on the natural history study data. And all of these milestones, I remind you, are typically never gained or regained past the age of 6.

好的。非常好。因此請移動幻燈片。謝謝。好的，正如 Suku 所提到的，使用獨立的中央評估者對 A 部分的數據進行了重新分析，以評估根據自然歷史研究數據分離出的這 28 個里程碑中任何發展里程碑的獲得或恢復。我還要提醒你，所有這些里程碑通常在 6 歲以後都無法達到或恢復。

And so all of the data that we currently had in the trial was reanalyzed based on video, so it was a very strict detection of gain or regained using predefined primary criteria. And so we were very pleased to see that all patients treated so far in the cohort have reached this criteria of gaining at least one milestone or regaining at least one milestone.

因此，我們目前在試驗中擁有的所有數據都是根據視訊重新分析的，因此這是使用預先定義的主要標準對增益或恢復進行的非常嚴格的檢測。因此，我們很高興地看到，迄今為止接受治療的所有患者都達到了至少獲得一個里程碑或重新獲得至少一個里程碑的標準。

And many patients actually gained more than one milestone, as you will observe in the next slides. But before we go on, I just want to point out that in the data we’re presenting here for the clinical assessments, we’re describing 10 patients. The two other patients were below the three month cutoff, so we didn’t have yet the clinical assessments to detect and conduct this evaluation.

正如您將在下一張幻燈片中看到的那樣，許多患者實際上取得了不止一個里程碑。但在繼續之前，我只想指出，在我們為臨床評估提供的資料中，我們描述了 10 名患者。另外兩名患者的病情還未達到三個月的臨界值，因此我們還沒有進行臨床評估來檢測和進行此項評估。

I also want to point out, when you look at the data, that, of course, the longer follow-up were for the low dose cohort. And so for the high dose cohorts, we have a shorter follow-up and many of them were still adolescents. So we’re eager to see the development of this data moving forward with the 12 months and 18 months cutoff for the high dose patients.

我還想指出，當你查看數據時，當然，較長的追蹤時間是針對低劑量組。因此，對於高劑量組，我們的追蹤時間較短，其中許多人仍是青少年。因此，我們迫切希望看到這些數據的發展，以及高劑量患者 12 個月和 18 個月的截止時間。

And so looking at the (inaudible) gains that we’ve observed in the cohorts so far, out of the 10 patients that were treated next slide -- out of the 10 patients that were treated, we’ve observed a gain of 22 developmental milestones, and these were across multiple domains of the disease, as illustrated here. And patients that gained milestones in one domain often gain also in other domains, so it’s not restricted to one single domain.

因此，看看我們迄今為止在隊列中觀察到的（聽不清楚）進展，在下一張幻燈片中接受治療的 10 名患者中 - 在接受治療的 10 名患者中，我們觀察到 22 個發展里程碑的進展，這些進展涉及疾病的多個領域，如這裡所示。在一個領域取得里程碑式進展的患者通常也會在其他領域取得進展，因此並不局限於單一領域。

And so 22 milestones out of 10 patients suggest that many patients gain more than one. The domains that we’ve observed with gains or regains are, for instance, in communication. We saw patients that are now able to use phrases to communicate, things like, Okay, bye, mom, whereby before they would use sparse words here and there or one single word very infrequently.

因此，每 10 名患者中就有 22 名達到了里程碑，這表明許多患者取得了不只一個里程碑。例如，我們觀察到的獲得或重新獲得的領域是溝通。我們看到患者現在能夠使用短語進行交流，例如“好的，再見，媽媽”，而之前他們只會偶爾使用零散的詞語或一個單字。

We’ve also seen patients learning to use words who had previously been nonverbal for communication. Many patients also gain the ability to follow command with a gesture or without the gesture, so more reactive to conversations around them and expectations, which really helps the daily routine of things like, going to brush your feet or eating meal or it’s time to prepare for school or nothing.

我們也看到患者正在學習使用以前無法用語言溝通的語言。許多患者也獲得了透過手勢或非手勢執行命令的能力，因此對周圍的對話和期望更加敏感，這確實有助於日常事務，例如去刷腳或吃飯或準備上學或什麼都不做。

Some patients have gained the ability to point to things they want or to identify body parts. This may seem like, just a basic task for anyone who has a typical development, but for patients with Rett, this is really critical because they’ve finally been able to point what they really want, so it really clarifies their needs and helps communication with the family and caregivers.

有些患者已經獲得了指向他們想要的東西或識別身體部位的能力。對於任何具​​有典型發展的人來說，這似乎只是一項基本任務，但對於患有 Rett 的患者來說，這確實至關重要，因為他們終於能夠指出他們真正想要的東西，因此它確實可以明確他們的需求並有助於與家人和護理人員進行溝通。

For identifying body parts, this is very helpful when patients are more cranky or crying and it’s very difficult to know if they have pain somewhere, if they can point that it’s the head or it’s the tooth or it’s the belly. It’s very helpful for caring for these patients. So communication was key, both receptive and expressive.

對於辨識身體部位，當患者情緒較為暴躁或哭泣時，這非常有用，因為很難知道他們是否在某個地方感到疼痛，他們是否可以指出是頭部、牙齒還是腹部。這對於照顧這些病人非常有幫助。因此，溝通是關鍵，既要接受，又要表達。

In terms of fine motor, we’ve seen patients gaining the ability to hold a bottle unpropped, so a real gain in autonomy and independence so that they would eventually be able to drink by themselves. To finger feed, once again with pincer grasp, this is a huge improvement in independence.

在精細動作方面，我們看到患者獲得了不用支撐就能拿住奶瓶的能力，因此他們真正獲得了自主性和獨立性，最終能夠自己喝水。用手指餵食，再次用鉗子抓握，這是獨立性的巨大進步。

Reaching for a toy and transferring objects from one hand to the other, very much helps manipulating objects when you’re holding or stabilizing with one hand you can manipulate with the other hand and eventually once you’re stabilized then participate to the task with both hands which is really key for independence and purposeful hand use.

伸手去拿玩具並將物體從一隻手轉移到另一隻手，非常有助於操縱物體，當您用一隻手握住或穩定時，您可以用另一隻手操縱，最終一旦您穩定下來，就可以用雙手參與任務，這對於獨立和有目的地使用手部至關重要。

In terms of gross motor skills, we’ve seen patients starting to be able to walk with support, to stand while holding up, to pull to a standing position, or to sit without support. All of these show real gains in terms of independence and mobility, and it reduces the physical burden of caregivers. And I’ll give you an example in the next slide, please.

在粗大動作技能方面，我們看到患者開始能夠在支撐下行走、扶著東西站立、拉起身體站起來或無需支撐就能坐下。所有這些都顯示出獨立性和機動性方面的真正進步，並減輕了護理人員的身體負擔。請在下一張投影片中舉例。

So as we were discussing clinical evolution with patients at each visit, we’re filming many of these assessments. And so from these films, on the next slides, we could capture quotes from the family and caregivers, which are illustrated here. And basically these really show how impactful these new gains were for these families. And so one patient told us all of our days are better, her improvements are much beyond anything we had expected or hoped for. So it’s so transformative that it really was across multiple aspects of their life.

因此，當我們每次與患者討論臨床進展時，我們會拍攝許多此類評估。因此，從這些影片中，在下一張投影片上，我們可以捕捉到來自家人和照護人員的引言，這些引言在這裡都有說明。基本上，這些確實顯示了這些新收穫對這些家庭的影響有多大。因此，一位患者告訴我們，我們的每一天都變得更好了，她的進步遠遠超出了我們的預期或希望。所以它具有如此大的變革性，確實影響了他們生活的多個面向。

She gained multiple words, no, yeah, mom, dad, and is making consistent sounds with meaning and even says some phrases, okay, bye, no more. And so it’s really a clear progress in communication for who previously was using a single word once in a while.

她學會了說多個單詞，不，是的，媽媽，爸爸，並且能發出一致且有意義的聲音，甚至能說一些短語，好的，再見，不再說了。因此，對於以前只是偶爾使用單字的人來說，這確實是一個明顯的溝通進步。

Another family told us she’s a lot easier to care for, she can point a lot more deliberately to make choices and to show us what she wants, and she will keep gesturing until we get it for her. She pushes away what she doesn’t want. And this is really, really key because on daily living, when they can finally really show what they actually want or mean, it reduces stress, reduces anxiety and it makes all interactions so much more pleasant for the kid and for the family.

另一個家庭告訴我們，她現在更容易照顧了，她可以更有意識地做出選擇，並向我們展示她想要什麼，而且她會一直做手勢，直到我們為她得到它。她會推開她不想要的東西。這真的非常關鍵，因為在日常生活中，當他們最終能夠真正表達出他們真正想要什麼或想要什麼時，就會減輕壓力，減少焦慮，並使孩子和家庭的所有互動變得更加愉快。

The ability to stand while holding on is really important. So this family told us it has been a godsend when it comes to toileting while out in the community because now I can have her stand and hang to my arm to toilet and wipe her.

堅持站立的能力確實很重要。所以這個家庭告訴我們，當她在社區外上廁所時，這真是天賜之物，因為現在我可以讓她站著，掛在我的手臂上廁所並給她擦屁股。

So of course, this is really helpful if a child can finally stand by them all their own even through holding. And the consistency of keeping our hands down without constant [stereotypes] allows us to practice more tasks such as using a walker, which has been huge.

因此，如果孩子最終能夠自己站在他們身邊，即使是透過抱著他們，這當然會很有幫助。並且，在沒有固定的[刻板印象]的情況下始終如一地放下雙手使我們能夠練習更多的任務，例如使用助行器，這非常重要。

So once again, better hand use can transfer into gross motor skill gains as well, where even this might not show up in the developmental gain skills that was described earlier, it is still a gain in practice because walking around with a walker is much more convenient than with somebody holding you and holding the trunk as you’re trying to move a few steps.

因此，再次強調，更好的手部使用能力也可以轉化為粗大運動技能的提高，即使這可能不會體現在前面描述的發展性技能提高中，但在實踐中仍然是一種提高，因為藉助助行器走路比當你試圖移動幾步時有人扶著你並扶著軀幹要方便得多。

Another family said her hands are more relaxed and she tries to grab everything with a racking grasp. She can follow directions in a snap like if we say, let go, she gets up and she heads to the door. She’s babbling now, which didn’t do before and it definitely is trying to tell us something. So you can see just from a few of these quotes how striking and broad the gains were, so it’s not restricted to one single domain.

另一個家庭說，她的手更加放鬆，她試著用力抓住一切。她可以立即聽從指示，例如如果我們說放手，她就會站起來並走向門口。她現在開始咿呀學語，這在以前是不會發生的，而且她肯定是想告訴我們一些事情。因此，您可以從這些引言中看出收益有多麼驚人和廣泛，因此它並不局限於單一領域。

The next slide, please. As we’re looking at the data across the various assessments, it became very clear that our high dose patients are performing better than the low dose, so they’re making their gains much faster. And so you can see from the green line here that 100% of the cohort of high dose reached at least one milestone within nine months, whereas it took a bit longer for the low dose patients. So the pace much increased, and you can imagine that these lines are still growing.

請翻到下一張投影片。當我們查看各種評估的數據時，很明顯，高劑量患者的表現比低劑量患者更好，因此他們的康復速度更快。因此，您可以從這裡的綠線中看到，100％的高劑量組患者在九個月內至少達到了一個里程碑，而低劑量患者則需要更長的時間。因此步伐大大加快，你可以想像這些線路仍在增長。

And so these patients are still being followed, and presumably we could expect that they’re still making progress, whereas the data we’re presenting is that the cutoff was made. And so this quicker gain may lead to better improvement on the long term as well.

因此，這些患者仍在接受隨訪，我們大概可以預期他們仍在取得進展，而我們呈現的數據表明，他們的病情已經到了臨界點。因此，這種更快的收益也可能帶來長期更好的改善。

Next slide. Apart from the developmental milestone evaluation that we described, we’ve done many other scales, both clinical scales and questionnaires to family. And so the next slide, please, is the one on the RMBA scale. And this is one of the scales that I personally really like because it’s a large broad scale of 24 items that it goes much beyond what we see for the RRSPQ.

下一張投影片。除了我們描述的發展里程碑評估之外，我們還做了許多其他量表，包括臨床量表和家庭問卷。下一張幻燈片是關於人民幣匯率的。這是我個人非常喜歡的量表之一，因為它包含 24 個項目，範圍很廣，遠遠超出了 RRSPQ 的範圍。

So the RRSPQ tends to be focused on communication and breathing and irritability and things like that. But the RMBA, please go back to the previous slide. RNBA is really 24 items across multiple domains, motor function, functional skills, social skills, aberrant behavior, and breathing, and it’s a total of 96 points.

因此，RRSPQ 傾向於關注溝通、呼吸、煩躁等問題。但是人民幣銀行，請回到上一張投影片。RNBA 實際上是涵蓋多個領域的 24 個項目，包括運動功能、功能技能、社交技能、異常行為和呼吸，總計 96 分。

So now on this slide that you’re showing, what we’ve observed across the cohort is a clear gain on this maximal of 96 points. We’ve seen a gain of 11 points at 6 months and 12.8 points at 12 months in the cohort, suggesting a very drastic improvement that is, of course, beyond one sickle domain because this scale really assessed very broadly multiple aspects of the disease.

現在，在您展示的這張投影片上，我們觀察到整個群體的得分明顯高於最高分 96 分。我們發現該隊列在 6 個月時增加了 11 分，在 12 個月時增加了 12.8 分，這表明改善非常顯著，當然，這超出了鐮狀細胞病的一個領域，因為這個量表實際上非常廣泛地評估了該疾病的多個方面。

And when we compare it to the natural history, this gain of 11 points at 6 months and of 12.8 points at 12 months is very, very striking. Please show the slide that I’m describing, which is this next one. Yes, this is the one where we see the score, 11 points improvement compared to natural history and 12.8 points at 12 months compared to natural history. So this is really unheard of and very striking in terms of the depth of the improvement. Next slide.

當我們將其與自然病史進行比較時，6 個月時增加 11 分，12 個月時增加 12.8 分，這是非常非常驚人的。請展示我正在描述的投影片，也就是下一張。是的，這是我們看到的分數，與自然史相比提高了 11 分，與自然史相比，12 個月時提高了 12.8 分。因此，就改進的深度而言，這確實是聞所未聞的，而且非常引人注目。下一張投影片。

The next scale that we’re showing is results from the CGII, and the CGII is this Clinical Global Impression Improvement Scale. This is the global impression that clinicians will share after taking into account everything that has been done at this visit, including the RMBA, the physical exam, SBQ, the hand function test, and all of the other assessments.

我們展示的下一個量表是 CGII 的結果，CGII 是臨床整體印象改善量表。這是臨床醫生在考慮到本次訪問所做的一切後會分享的總體印象，包括 RMBA、體檢、SBQ、手部功能測試和所有其他評估。

And we’re really looking for changes across the seven domains of the disease, so motor, fine motor, language, communication, breathing, autonomic dysfunction, epilepsy. And so it’s also a very broad scale. And so next slide, what we’ve observed in our cohort is an improvement in all patients on the scale.

我們真正想要尋找的是該疾病七個領域的變化，即運動、精細運動、語言、溝通、呼吸、自主神經功能障礙、癲癇。因此它的規模也非常廣泛。在下一張投影片中，我們觀察到我們的隊列中所有患者的病情都有改善。

And once again, the high dose patients overperform compared to the low dose patients. So the high dose patients reached one, which is a scale that suggests very much improved by 9 months of follow-up, whereas in the low dose patients we were around 3 and eventually 2, so 2 being much improved and 3 is minimally improved. So we do see gains in all the cohorts, even in adolescents and adults, even treated with a low dose, but the depth of the gain and the rapidity of the gain is greater in the patients treated with a high dose.

再次，高劑量患者的表現優於低劑量患者。因此，高劑量患者達到了 1，這是一個顯示在 9 個月的追蹤中病情得到很大改善的量表，而在低劑量患者中，我們的量表約為 3，最終為 2，因此 2 表示有很大改善，3 表示改善很小。因此，我們確實看到所有群體，甚至青少年和成年人，即使接受低劑量治療，都有所改善，但接受高劑量治療的患者改善的深度和速度更大。

The next slide, please. This slide summarizes the full dataset comparing the low dose and the high dose that really illustrates many of the points that I’ve shared today. First of all, all of the patients were responder based on this developmental milestone assessment, so 100% of low dose and high dose cohort reached at least one milestone, and this was achieved faster in the high dose cohort.

請翻到下一張投影片。這張投影片總結了比較低劑量和高劑量的完整數據集，真正說明了我今天分享的許多觀點。首先，根據這項發展里程碑評估，所有患者都是有反應的，因此低劑量和高劑量組 100% 都達到了至少一個里程碑，而高劑量組實現這一目標的速度更快。

In terms of the RNDA, as I mentioned, all of them improved and improved quite strikingly. So we see in the low dose at 6 months 9.8 points, and at 9 months, 11.5 points on a 96 scale, which is a very striking improvement. In the high dose, you can see that the depth of improvement is even greater, so we’re reaching an 18 improvement at more than 9 months.

就 RNDA 而言，正如我所提到的，它們都得到了改進，而且改進相當顯著。因此，我們看到低劑量組在 6 個月時得分為 9.8 分，在 9 個月時得分為 11.5 分（滿分 96 分），這是一個非常顯著的改善。在高劑量下，您可以看到改善的深度更大，因此我們在 9 個多月內達到了 18% 的改善。

Then in terms of CGII, as I mentioned, all patients improved. So at the cutoff, we had 75% of patients in the low dose that had improved on the CGII scale and 100% of the high dose. And as a mean, we’re observing at 6 months 2.3 and at 9 months 2.8 in the low dose, and those are much improved, between the much improved and minimally improved grades, whereas for the high dose, we’re reaching a much improved grade at 6 months and very much improved grade at more than 9 months. So we are gaining even more.

然後就 CGII 而言，正如我所提到的，所有患者的情況都有所改善。因此，在截止點，低劑量組 75% 的患者 CGII 量表有所改善，高劑量組 100% 的患者 CGII 量表有所改善。平均而言，我們觀察到低劑量組 6 個月時為 2.3，9 個月時為 2.8，這些等級在「大幅改善」和「輕微改善」之間都有了很大的提高，而高劑量組在 6 個月時達到了「大幅改善」的等級，在 9 個月以上時達到了「非常大幅改善」的等級。因此我們收穫的更多。

Now in terms of the [CGIS], this is the severity score, which once again looks at seven aspects of the disease and grades the ability of the patients in a broader fashion. And it’s usually very hard to change grades of the CGIF because you need very striking gains to switch one item out of that grid.

現在就 [CGIS] 而言，這是嚴重程度評分，它再次考察疾病的七個方面，並以更廣泛的方式對患者的能力進行評級。而且通常很難改變 CGIF 的等級，因為您需要非常顯著的收益才能將一個項目從該網格中移除。

And so we observed thirty three percent of the high dose cohort changing severity to a better grade and 25% changing also in the low dose. So in both cohorts, we’ve observed patients improving so much that they were able to switch scores for the CGIS.

因此，我們觀察到高劑量組的 33% 病情嚴重程度有所改善，低劑量組的 25% 病情嚴重程度也有所改善。因此，在這兩個群體中，我們都觀察到患者的病情有了很大的改善，以至於他們能夠轉換 CGIS 分數。

Last slide. So in total, we’ve observed that TSHA-102 has been, generally very well tolerated, both in the low and the high dose. There has been no dose limiting toxicities or treatment induced serious adverse events. We’ve observed, of course, some treatments induced adverse events associated to TSHA-102.

最後一張投影片。因此，總的來說，我們觀察到，無論低劑量或高劑量，TSHA-102 的耐受性通常都非常好。沒有出現劑量限制毒性或治療引起的嚴重不良事件。當然，我們觀察到一些治療引起了與 TSHA-102 相關的不良事件。

Most of them were in the mild, some were in the moderate and severity range. The most frequent ones were elevated liver enzymes, when we saw those, the majority were below two times the upper limit of normal, and a few patients did have more acute excursions above five times, but they all responded to steroid treatment and recovered without sequel life.

其中大部分屬於輕度，部分屬於中度及重度範圍。最常見的是肝酵素升高，當我們看到這些時，大多數都低於正常上限的兩倍，少數患者確實出現了超過五倍的急性波動，但他們都對類固醇治療有反應並且康復，沒有後遺症。

Other side effects that were observed associated with TSHA-102 are side effects expected for AAV therapies, so fever, lethargy after the lumbar puncture treatment, and increase in protein in the CSF. Overall, (inaudible) were well controlled in this cohort. So I’m done with my slides and I’m moving the call back to the Taysha team.

與 TSHA-102 相關的其他副作用是 AAV 療法預期的副作用，因此發燒、腰椎穿刺治療後嗜睡以及腦脊髓液中蛋白質增加。總體而言，（聽不清楚）在這個群體中得到了良好的控制。我的幻燈片已經製作完畢，我將把電話轉回給 Taysha 團隊。

Thank you, Dr. Rosignol. Research and development expenses were $2.1 million for the three months ended June 30, 2025, compared to $15.1 million for the three months ended June 30, 2024. The $5 million increase was driven by BLA enabling process performance qualification manufacturing initiatives, REVEAL clinical trial activities and higher compensation expenses as a result of increased headcount during the three months ended June 30, 2025. General and administrative expenses were $8.6 million for the three months ended June 30, 2025, compared to $7.3 million for the three months ended June 30, 2024.

謝謝您，羅西尼奧爾博士。截至 2025 年 6 月 30 日的三個月，研發費用為 210 萬美元，截至 2024 年 6 月 30 日的三個月為 1,510 萬美元。500 萬美元的增長是由於 BLA 支持工藝性能鑑定製造計劃、REVEAL 臨床試驗活動以及截至 2025 年 6 月 30 日的三個月內員工人數增加導致的薪酬費用增加。截至 2025 年 6 月 30 日的三個月，一般及行政費用為 860 萬美元，而截至 2024 年 6 月 30 日的三個月，一般及行政費用為 730 萬美元。

The increase of $1.3 million is primarily due to higher legal and professional fees. Net loss for the three months ended June 30, 2025, was $26.9 million or $0.9 per share compared to a net loss of $20.9 million or $0.9 per share for the three months ended June 30, 2024.

130萬美元的增加主要是由於法律和專業費用的增加。截至 2025 年 6 月 30 日的三個月淨虧損為 2,690 萬美元，即每股 0.9 美元，而截至 2024 年 6 月 30 日的三個月淨虧損為 2,090 萬美元，即每股 0.9 美元。

As of Juen 30, 2025, Taysha had $312.8 million in cash and cash equivalents. This reflects gross proceeds of $230 million from the May 2025 follow on financing, which includes the full exercise of the underwriters’ option to purchase additional shares. We also refinanced our existing loan and security agreement with Trinity Capital from the original $40 million which was paid in full to a net new debt facility equal to $50 million upfront.

截至 2025 年 6 月 30 日，Taysha 擁有 3.128 億美元的現金和現金等價物。這反映了 2025 年 5 月後續融資的總收益 2.3 億美元，其中包括承銷商充分行使購買額外股份的選擇權。我們也對與 Trinity Capital 簽訂的現有貸款和擔保協議進行了再融資，從最初的 4000 萬美元（已全額支付）變為一筆相當於 5000 萬美元預付款的淨新債務融資。

The refinance loan defers debt principal payments by more than 2.5 years, lowers our interest rates and provides access to non-dilutive capital. Importantly, there continue to be no financial liquidity covenants or warrants associated with the new refinance loan with Trinity. We look forward to our continued partnership with the Trinity Capital team.

再融資貸款將債務本金支付推遲了 2.5 年以上，降低了我們的利率，並提供了非稀釋性資本。重要的是，與 Trinity 的新再融資貸款相關的金融流動性契約或認股權證仍然不存在。我們期待與 Trinity Capital 團隊繼續合作。

We expect our current cash resources to support planned operating expenses and capital requirements into 2028. I will now turn the call over to Sean for his closing remarks. Sean?

我們預計目前的現金資源將能夠支援到 2028 年的計劃營運費用和資本需求。現在我將把電話交給肖恩，請他作結束語。肖恩？

Thanks, Kamran. I’m pleased with the progress we have continued to make to advance our TSHA-102 program. With a strengthened balance sheet, our FDA aligned pivotal trial underway and compelling clinical data from Part A, we are moving forward with confidence as we work to deliver on our anticipated near term milestones.

謝謝，卡姆蘭。我很高興看到我們在推進 TSHA-102 計劃方面不斷取得進展。憑藉增強的資產負債表、正在進行的符合 FDA 的關鍵試驗以及來自 A 部分的令人信服的臨床數據，我們正滿懷信心地向前邁進，努力實現我們預期的近期里程碑。

This includes beginning patient enrollment for our pivotal trial in the fourth quarter of this year. We also plan to report new supplemental clinical data from Part A of our REVEAL Phase 1/2 trials supporting the broad therapeutic impacts of TSHA-102 in the fourth quarter of this year.

這包括在今年第四季開始招募我們關鍵試驗的患者。我們也計劃在今年第四季報告 REVEAL 1/2 期試驗 A 部分的新補充臨床數據，以支持 TSHA-102 的廣泛治療效果。

We truly appreciate the collaborative interactions with the FDA and Health Canada to date and believe this progress advances our goal to bring TSHA-102 to patients with this devastating disease as expeditiously and safely as possible.

我們非常感謝迄今為止與 FDA 和加拿大衛生部的合作互動，並相信這一進展將推動我們實現目標，即盡可能迅速、安全地將 TSHA-102 帶給患有這種毀滅性疾病的患者。

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

現在我請接線生開始我們的問答環節。操作員？

(Operator Instructions)

（操作員指示）

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Hi, good morning. This is Lydia on for Salveen. Thanks so much for taking our question. I guess given there was 100% response rate for the pivotal trial primary endpoint in the Part A of the study, is this the bar for Part B in your view? Thanks so much.

嗨，早安。這是 Salveen 的 Lydia。非常感謝您回答我們的問題。我想，鑑於研究 A 部分中關鍵試驗主要終點的反應率為 100%，您認為這是 B 部分的標準嗎？非常感謝。

I think that the results we’ve seen in Part A are exceptionally compelling. I think 100% is always a difficult standard to keep. I think what’s the most important thing is how we build the statistical plan for Part B and keep in mind that we’re using a null hypothesis of 6.7%, which was the highest percentage of a gain regain per milestone that we’re evaluating.

我認為我們在第一部分中看到的結果非常引人注目。我認為 100% 始終是一個難以維持的標準。我認為最重要的是我們如何為 B 部分制定統計計劃，並記住我們使用的是 6.7% 的零假設，這是我們評估的每個里程碑收益恢復的最高百分比。

And when you take that into account with a 15 patient population that would mean 1 patient out of 15 would spontaneously have a potential gain or regain. So the statistical bar to get over is relatively low. All things speaking, it’s approximately 33% based on our submission of the SAP. So what gives us a lot of confidence is that the numbers that we’re seeing so far play out in Part A are consistent and significantly above that threshold. Thank you.

如果將這種情況考慮在內，以 15 名患者為例，這意味著每 15 名患者中就有 1 名會自發性地獲得或恢復潛在的體重。因此，需要克服的統計門檻相對較低。總而言之，根據我們提交的 SAP，這個比例大約是 33%。因此，讓我們充滿信心的是，到目前為止，我們在 A 部分看到的數字是一致的，並且遠高於該閾值。謝謝。

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

Hi, good morning. I’ll ask my question for Dr. Rosignol. So it was encouraging to hear that other milestones have been reported that weren’t necessarily as part of the video assessments. But can you help us understand, is there a certain time point where all these milestones are occurring by? Are you seeing additional ones occur over the long span of time? Just trying to get a sense of whether or not you think the benefits of the gene therapy have plateaued yet.

嗨，早安。我要向羅西尼奧爾博士提問。因此，聽到其他里程碑的報導並不一定是影片評估的一部分，這是令人鼓舞的。但是您能否幫助我們理解，所有這些里程碑事件是否都會在某個時間點發生？您是否看到在很長一段時間內還會發生其他類似的情況？只是想了解您是否認為基因療法的益處已經達到穩定水平。

Elsa, please feel free to take that.

艾爾莎，請隨意拿著。

Yes, so thank you for the question. If you look at the data that we have so far up to the cutoff, we were seeing increasing improvement as we were following the patients. And so we’re expecting a similar increase in gains over the time course since that last cutoff. So this does not occur just in one visit, and we do see gains usually at most visits in follow-up.

是的，謝謝你的提問。如果你查看我們迄今為止掌握的截止數據，你會發現，隨著我們對患者的跟踪，病情正在不斷改善。因此，我們預計自上次截止以來，收益將隨著時間的推移而出現類似的增長。因此，這不僅發生在一次訪問中，而且我們通常會在後續的大多數訪問中看到收益。

And when we were mentioning the gains that are not observed or quantified in this developmental milestone assessment, what I meant by that is if you’re now able to walk with a walker, that doesn’t give you a point on the developmental milestone skills because you would need to walk independently. So we can have critical gains that improve daily functioning that are not captured in this skill set, but are still major and critical improvements.

當我們提到在這個發展里程碑評估中沒有觀察到或量化的收益時，我的意思是，如果你現在能夠借助助行器行走，這並不會在發展里程碑技能方面給你加分，因為你需要獨立行走。因此，我們可以獲得改善日常功能的關鍵收益，這些收益雖然不包含在該技能組合中，但仍是重大且關鍵的改進。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi, guys. Good morning. Thanks for taking my question. I wanted to maybe talk about the differentiation of your gene therapy versus your competitor. In particular, maybe I could get the doctor’s view on study design. So you’re looking at a smaller cohort and you’re also looking at a single primary endpoint. Can you talk about the differences in these studies and how you think this could lead to differentiation between the two programs? Thanks.

嗨，大家好。早安.感謝您回答我的問題。我想談談你們的基因療法與競爭對手的差異。特別是，也許我可以了解醫生對研究設計的看法。因此，您正在查看較小的群體，並且您也在查看單一主要終點。您能談談這些研究之間的差異嗎？您認為這將如何導致這兩個項目之間的差異？謝謝。

Yes. Thanks, Stacy. It’s good to hear from you. Suku, maybe we can tag team this. I think first and foremost is the fact that the way we conducted the Part A trial was to cast a broad net. It was really the first in human trial to let us explore what are some of the different efficacy measures that would make a lot of sense. And all along the way, we’ve always been at the mind that with the gene therapy, you really have to show something clinically meaningful and objective that’s going to impact activities of daily living, i.e., you can go back two years and hear Suku talk about small gains and scales are not going to be the mark that we’re looking for.

是的。謝謝，史黛西。很高興收到您的來信。Suku，也許我們可以組隊。我認為，首先也是最重要的一點是，我們進行 A 部分試驗的方式是廣撒網。這其實是首次進行人體試驗，讓我們來探索一些非常有意義的不同功效測量方法。一路走來，我們始終堅信，基因治療必須真正展現出具有臨床意義和客觀性的效果，能夠影響日常生活活動。也就是說，你可以回到兩年前，聽到 Suku 談論小小的進步和規模，但這絕不是我們所期待的標誌。

And so, I think the fact that we’ve been working with the regulators to establish a completely new paradigm in assessing clinical efficacy, which is the gain and regain of milestones. This is functional gains that have never been achieved before in this disease. And so we’re redefining a -- how we’re going about defining what truly is impactful from a clinical perspective and from a patient and caregiver perspective.

因此，我認為我們一直在與監管機構合作，建立一個評估臨床療效的全新範例，即里程碑的獲得和重新獲得。這是該疾病中從未實現過的功能增益。因此，我們正在重新定義——如何從臨床角度、患者和照護者的角度來定義什麼是真正有影響力的。

And I think the approach that we’re taking is exceptionally unique. We’ve been very enthused by the -- I would say that just the support we’ve got, the excitement that we’ve gotten from the KOLs that participated in the natural history, people participating in the study, advocacy, everyone is just very excited because they see how this can truly impact their quality of life.

我認為我們採取的方法非常獨特。我們對此感到非常興奮——我想說的是，我們所獲得的支持，以及我們從參與自然歷史的關鍵意見領袖、參與研究的人們和倡導者那裡得到的興奮，每個人都非常興奮，因為他們看到了這將如何真正影響他們的生活品質。

So I think when you look at things broadly, Tazeen, we’re in a situation where we’re capturing milestones where we can clearly show an effect that’s going to mean a lot with payers as well. And then the additional endpoints that we’re looking at relative to rMDA CGI, again we can benchmark RMBA to the natural history and it’s exceptionally compelling.

因此，Tazeen，我認為，當你從更廣泛的角度來看待問題時，我們正處於這樣一種境況：我們正在捕捉里程碑，我們可以清楚地展示出對付款人也意義重大的效果。然後，我們正在研究相對於 rMDA CGI 的其他端點，我們可以再次將 RMBA 與自然歷史進行對比，這非常引人注目。

I mean effectively natural history is about 0, right? It just doesn’t move. It doesn’t get any better and we’re showing that it’s better. Again, that’s going to help with the excitement in the community, that’s going to help with the payers and supporting them.

我的意思是自然歷史實際上約為 0，對嗎？它就是不動。情況並沒有變得更好，而我們正在證明情況正在變得更好。再次，這將有助於激發社區的熱情，這將有助於付款人並為他們提供支持。

And I think you combine the efficacy impact that you’re seeing with the safety that we’ve been able to generate today and we think that is very much attributed to two things. One is CMC quality and two would be the route of administration really minimizes the amount of systemic exposure that these patients receive.

我認為，將所看到的功效影響與我們今天能夠產生的安全性結合起來，我們認為這主要歸功於兩件事。一是 CMC 質量，二是給藥途徑確實最大限度地減少了這些患者所接受的全身暴露。

So we think for all those reasons, this is going to be a very enticing offer to patients and they’re going to want to do what’s easiest and safest for their kids and also that demonstrates a significant effect that can change the way that their daily life is lived.

因此，我們認為，出於所有這些原因，這對患者來說將是一個非常有吸引力的選擇，他們會想為他們的孩子做最簡單、最安全的事情，而且這也顯示出可以改變他們日常生活方式的顯著效果。

Sean, I would add one more thing to Tazeen. By the way, nice to hear your voice. I just want to again emphasize at Taysha, we are clearly committed to the patients with Rett syndrome and that’s what we’ve done, really paying attention to safety and clinical meaningfulness of our product with a minimally invasive route of administration. So having said that and you’ve already seen the data that Dr. Elsa Rosignol presented and what Sean just said.

肖恩，我想向塔津補充一點。順便說一句，很高興聽到你的聲音。我只是想再次強調，在 Taysha，我們明確致力於為患有 Rett 綜合徵的患者服務，這就是我們所做的，我們真正關注產品的安全性和臨床意義，並採用微創給藥途徑。話雖如此，您也已經看到了 Elsa Rosignol 博士提供的數據以及 Sean 剛才所說的內容。

As far as commenting on Neuogen’s protocol, I would say for full disclosure and disclaimer, I really don’t know what their protocol is yet other than what’s in the public domain. It appears to be a single arm study. They had a composite endpoint for their primary, but it’s not clear that that’s still the case based on what was disclosed just this week.

至於 Neuogen 協議的評論，我想說，為了全面披露和免責聲明，除了公共領域的內容之外，我真的不知道他們的協議是什麼。這似乎是一項單臂研究。他們有一個主要的綜合終點，但根據本週披露的信息，尚不清楚情況是否仍然如此。

I would also go further to say that the natural history data set that we have. I have never seen such a comprehensive and a large natural history data set to do an appropriate assessment of and it’s a 14 year period.

我還想進一步說，我們擁有自然史資料集。我從未見過如此全面和龐大的自然歷史資料集來進行適當的評估，而且這是一個長達 14 年的時間跨度。

So given our experience in looking at this data set, it’s very clear that once you get above the age of 6 and you do a therapeutic intervention such as TSHA-102 and as Sean highlighted and Dr. Rosignol highlighted, when you see a gain of a new skill or regain of a lost skill, the odds are very likely it’s the patient gene therapy intervention. And we’ve seen patients actually change their lives by gaining these skills or developmental milestones and having an improvement in the activities of daily living.

因此，根據我們查看該數據集的經驗，很明顯，一旦你超過 6 歲並且進行了 TSHA-102 等治療幹預，正如 Sean 和 Rosignol 博士所強調的那樣，當你看到獲得一項新技能或重新獲得一項失去的技能時，很有可能這是患者基因治療幹預的結果。我們看到患者透過獲得這些技能或發展里程碑以及改善日常生活活動，真正改變了他們的生活。

Things that I would say that I take for granted by getting up in the morning brushing my teeth, feeding myself and putting my shirt on most of these patients whether they’re young or old cannot do. So having that ability to change their lives in such a manner and work with the advocacy groups and the physicians who are experts in this field and the regulators such as the FDA gives us a lot of satisfaction having come back to do this for TSHA-102 and the patient population. So thank you.

我想說，我認為早上起床刷牙、自己吃飯、穿衣服是理所當然的事情，但大多數病人，無論年老或年輕，都做不到。因此，能夠以這種方式改變他們的生活，並與倡導團體和該領域的專家醫生以及 FDA 等監管機構合作，讓我們非常滿意地再次為 TSHA-102 和患者群體做這件事。所以謝謝你。

Gil Blum, Needham and Company.

吉爾布魯姆，尼德漢姆公司。

Hey guys, this is Ethan on for Gil. Congratulations on the progress this quarter. So your competitor recently received regulatory feedback that a 6 month endpoint would not be considered clinically meaningful in their case. Obviously, your study designs are slightly different, but would you expect any pushback on using your interim readout to support BLA filing or was that already discussed with the FDA as well? Thank you.

大家好，我是 Ethan，代替 Gil 發言。恭喜本季取得的進展。因此，您的競爭對手最近收到監管回饋，即 6 個月的終點在他們的情況下不會被認為具有臨床意義。顯然，您的研究設計略有不同，但您是否預計使用中期讀數來支持 BLA 備案會遇到任何阻力，或者是否已經與 FDA 討論過這個問題了？謝謝。

Yeah, it was part of our submission and I would say a couple of things and we can only speak to the Taysha interactions and feedback. But one of the things that we really try to highlight in Suku’s presentation, Elsa’s presentation is that we’ve taken a very data driven approach. And so when you think about what underlies our interim analysis approach is the fact that it’s based on the proof of concept analysis of the Part A data, which provides very robust support for the primary endpoint of both 6 months and 12 months.

是的，這是我們提交的一部分，我想說幾件事，我們只能談談 Taysha 的互動和回饋。但我們在 Suku 和 Elsa 的演示中真正試圖強調的一點是，我們採取了一種非常以數據為導向的方法。因此，當您思考我們的中期分析方法的基礎時，您會發現它是基於 A 部分數據的概念驗證分析，這為 6 個月和 12 個月的主要終點提供了非常強大的支持。

And then when you apply the data that also went through against the statistical plan that we talked about, there’s a clear difference between what the statistical threshold for success would be at 6 months and what we’re actually seeing.

然後，當您應用與我們討論的統計計劃相符的數據時，您會發現 6 個月的成功統計閾值與我們實際看到的結果之間存在明顯差異。

So recall one of the slides that also went through showed at 6 months of the high dose there is an 83% responder rate at 6 months and then that improves and deepens over the course of 12 months. So it’s something that I think from a data perspective, we really leverage with the FDA as the rationale as to why you could do a 6 month interim.

因此回想一下，其中一張投影片也顯示，在高劑量治療 6 個月時，反應率為 83%，然後在 12 個月內改善和加深。因此，我認為從數據角度來看，我們確實可以利用 FDA 作為進行 6 個月中期測試的理由。

I can tell you we’ve had discussions with them. It’s really at this point focused on further refinements of the actual analysis, but we have not been pushed off the ball about doing a six month interim. It’s more the particulars of the assessments. So we feel good about where we stand at this particular point in time.

我可以告訴你我們已經與他們進行了討論。目前，我們的重點是進一步完善實際分析，但我們並沒有被迫進行為期六個月的中期分析。這更多的是評估的細節。因此，我們對目前所處的位置感到滿意。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特 (Maury Raycroft)，傑富瑞 (Jefferies)。

Good morning. This is James on for Maury. Congratulations on the progress this quarter and thanks for taking our questions. Can you talk about expectations for the new supplemental REVEAL Part A data in Q4? Could we get additional data points like more granular information on the number of video documented milestones gained across the high and the low dose or individual CGI data points? Do you anticipate that the data will be at a medical conference or a company update?

早安.這是詹姆斯 (James) 代替莫里 (Maury) 上場。恭喜本季取得的進展，並感謝您回答我們的問題。您能談談對第四季度新的補充 REVEAL Part A 數據的期望嗎？我們能否獲得額外的數據點，例如有關高劑量和低劑量或單個 CGI 數據點的視頻記錄里程碑數量的更詳細資訊？您是否預計這些數據會出現在醫學會議或公司更新中？

I can see it being at both medical conference and the company update. And we’ll provide more specifics over the coming weeks and months leading into it James. But there’s a lot of information that we captured as I mentioned earlier and we cast a pretty wide net and some of that net also included additional videos that we haven’t talked about different ways to get at the milestone gain.

我可以看到它同時出現在醫學會議和公司更新中。我們將在未來幾週和幾個月內提供更多具體細節，詹姆斯。但正如我之前提到的，我們捕獲了大量信息，並且我們撒下了一張相當廣泛的網，其中一些還包括額外的視頻，我們還沒有討論過實現里程碑收益的不同方法。

And so we want to share with the community additional milestones and what those look like, how those translate into activities of daily living. And I think it will give a more fulsome picture of just exactly how the milestones are translating to improvements in activities of daily living and improvements of quality of life of the patients that have been treated thus far.

因此，我們希望與社區分享更多的里程碑以及它們是什麼樣子的，以及如何將它們轉化為日常生活活動。我認為它將更全面地展示這些里程碑如何轉化為日常生活活動的改善以及迄今為止接受治療的患者的生活品質的改善。

Biren Amin, Piper Sandler.

比倫阿明、派珀桑德勒。

Yeah. Hi, guys. Thanks for taking my questions. Can you maybe characterize any changes from the Part A CMC material batch to Part B CMC material with, I guess, a specific emphasis on full to empty capsid ratio across both batches? And with the commercial scale of material. What are your thoughts in terms of how many patients you can supply into the market when approval comes in? Thanks.

是的。嗨，大家好。感謝您回答我的問題。您能否描述一下從 A 部分 CMC 材料批次到 B 部分 CMC 材料的任何變化，我想，特別強調一下這兩個批次的滿衣殼與空衣殼的比例？並具備材料的商業規模。當獲得批准後，您認為可以向市場供應多少患者？謝謝。

Yeah, Biren, as you know, it’s a massive opportunity, right. I just in The US. If we’re talking around 10,000 patients, it’s a massive unmet need. So it’s very important from our perspective and we’ve been working as a team.

是的，Biren，如你所知，這是一個巨大的機會，對吧。我剛剛在美國。如果我們談論的是大約 10,000 名患者，那麼這是一個巨大的未滿足需求。所以從我們的角度來看這非常重要，我們一直在團隊中合作。

Unfortunately, we have an excellent leader, Fred Porter, leading the effort for us to A, make sure we’re making the highest quality product and B, that we’re doing it at scale. And so, I think first and foremost, it’s important to note that we’ve aligned with the FDA, I think we said this a few quarters ago, that the Part A and the pivotal material are analytically comparable, which very important.

不幸的是，我們有一位出色的領導者，弗雷德·波特 (Fred Porter)，帶領我們努力做到 A，確保我們生產出最高品質的產品；B，確保我們能夠大規模地生產。因此，我認為首先，重要的是要注意我們已經與 FDA 保持一致，我想我們在幾個季度前就說過，A 部分和關鍵材料在分析上是可比的，這非常重要。

We’ve already made the products for the pivotal trial. We’ve shared that with the FDA. That’s made with the commercial process at scale and the FDA has said you can go into the clinic with that. So certainly, one of the things that we did with and are thinking about this is, we could have extended our cash runway into mid-2028, because of the combination of the raise that we did and Cameron’s good work with reworking the Trinity loan. But what we opted to do was to just basically keep send the guidance into 2028.

我們已經為關鍵試驗生產了產品。我們已經與 FDA 分享了這一訊息。這是透過大規模商業流程製造的，FDA 表示可以將其用於臨床。因此，可以肯定的是，我們已經採取並正在考慮的措施之一是，我們可以將現金流延長至 2028 年中期，這得益於我們所做的加薪以及卡梅倫在重新制定三一貸款方面的出色工作。但我們選擇的做法基本上是繼續將指導意見發送至 2028 年。

So in the situation where we’re able to move things forward more quickly with regulators, we could really work to begin to build the commercial inventory that we need. So we’ve got that as a contingency, we’ve got the funds to do it and we feel very strongly that we’re in a good position on the CMC side at this point.

因此，在我們能夠與監管機構一起更快地推動事情進展的情況下，我們可以真正努力開始建立我們所需的商業庫存。因此，我們已將其作為應急措施，我們有足夠的資金來實現這一目標，並且我們強烈感覺到，目前我們在 CMC 方面處於有利地位。

Jack Allen, Baird.

傑克艾倫，貝爾德。

Great. Thanks for taking the questions and congrats on the update here, very whole holistic update. I guess I wanted to ask just more specifically on your recent interactions with regulators. It seems like you have signed off from the Canadian authorities, but I wanted to understand where it sits as it relates to the IND amendment with the FDA and any ongoing discussions there?

偉大的。感謝您回答問題，並祝賀這裡的更新，非常全面的更新。我想更具體地詢問您最近與監管機構的互動。看起來您已經從加拿大當局簽署同意了，但我想了解它與 FDA 的 IND 修正案的關係以及那裡正在進行的討論？

What are the points of conversation as it relates to those conversations? If they’re ongoing or have you achieved a formal sign off? Where do things sit there? And then any additional color around European regulatory discussions would be interesting as well? Thank you so much.

與這些對話相關的對話重點是什麼？它們是否正在進行中或您是否已獲得正式簽署？那裡的東西放在哪裡？那麼有關歐洲監管討論的任何附加內容也會很有趣嗎？太感謝了。

Yes, Jack, great question. So a couple of things and Suku checked me on this, but basically number one, there’s a difference just in process. So with Health Canada, we did an amendment to the CTA and they have a 37 day review period and you if there’s no issues, you get what’s called a no objection letter or an NOL. And we got a no objection letter on day 37 with no comments. That means you’re good to go.

是的，傑克，這個問題問得好。所以有幾件事，Suku 也向我核實過，但基本上第一點，只是在流程上有差異。因此，我們與加拿大衛生部合作，對 CTA 進行了修訂，他們設定了 37 天的審查期，如果沒有問題，您將收到所謂的無異議函或 NOL。我們在第 37 天收到了一封無異議信，沒有任何評論。這意味著你已經準備好出發了。

I mean, also is working through things with our site right now as an example and that’s the process up in Canada. In the US, with the FDA because we did an IND amendment, there is no official correspondence that you get, there is no letter that you get. There is generally an unofficial 30 day, if you don’t hear something you can proceed.

我的意思是，現在我們正在透過我們的網站來處理事情，這就是加拿大的流程。在美國，由於我們對 FDA 進行了 IND 修訂，因此您不會收到任何官方信函，也不會收到任何信件。通常有非正式的 30 天時間，如果您沒有收到任何訊息，您可以繼續。

We were told early on, this would have been back in early, I guess, July. We received correspondence that there was no clinical hold concerns that we could proceed at our discretion. Subsequently, we’ve had interactions with the FDA with information requests and things of that nature.

我們很早就被告知，這應該會在七月初發生。我們收到信函稱，不存在臨床暫停問題，我們可以自行決定繼續進行。隨後，我們與 FDA 就資訊請求和諸如此類的事情進行了互動。

And I would characterize it as our view is that really it’s like further alignment is what we’re looking for that the ongoing FDA dialogue is focusing on how we position the program for success versus getting into overturning any key trial design elements or things of that nature. So it’s very constructive and supportive.

我認為我們的觀點是，我們真正尋求的是進一步的協調，正在進行的 FDA 對話的重點是如何定位該計劃以獲得成功，而不是推翻任何關鍵的試驗設計要素或類似的事情。所以它非常具有建設性和支持性。

As it relates to Europe, we do have a scientific advice meeting scheduled for this early fall and we’re continuing to work to enable that geography. So we should have more information when we give our next earnings call. Thanks for the question.

至於歐洲，我們確實計劃在今年初秋舉行科學諮詢會議，我們將繼續努力為該地區提供支援。因此，當我們下次召開財報電話會議時，我們應該會獲得更多資訊。謝謝你的提問。

Thank you. Ladies and gentlemen, we take that as the last question and conclude the question and answer session. I would now hand the conference over to Mr. Sean Nolan for his closing comments.

謝謝。女士們、先生們，我們將此作為最後一個問題，並結束問答環節。現在我將會議交給肖恩諾蘭先生，請他發表閉幕詞。

Just want to thank everyone for their time this morning, including our special guest, Doctor. Elsa Rosignol. We wish you all a great week. Take care and we’ll talk soon.

只想感謝大家今天早上抽出時間，包括我們的特別嘉賓醫生。艾爾莎·羅西尼奧爾。祝大家有個愉快的一周。保重，我們很快再談。

Thank you. Ladies and gentlemen, the conference of Taysha Gene Therapies has now concluded. Thank you for your participation. You may now disconnect your lines.

謝謝。女士們、先生們，Taysha 基因治療會議現已結束。感謝您的參與。現在您可以斷開線路了。