Applied Genetic Technologies Corp (AGTC) 2022 Q2 法說會逐字稿

Good morning, and welcome to the AGTC financial results conference call for the second quarter of fiscal year 2022. Today's call is being recorded.

早上好，歡迎參加 AGTC 2022 財年第二季度財務業績電話會議。今天的電話會議正在錄音中。

Before we get started, I would like to remind everyone that during this call, AGTC may make forward-looking statements, including statements about the company's financial results, financial guidance, its future business strategies and operations and its product development and regulatory progress, including statements about the timing and outcomes from data expected in its Skyline and Vista trials and the type of data that may support registration and potential approval.

在我們開始之前，我想提醒大家，在本次電話會議期間，AGTC 可能會做出前瞻性陳述，包括有關公司財務業績、財務指導、未來業務戰略和運營及其產品開發和監管進展的陳述，包括關於其 Skyline 和 Vista 試驗中預期數據的時間和結果的聲明，以及可能支持註冊和潛在批准的數據類型。

Actual results could differ materially from those discussed in these forward-looking statements due to a number of important factors, including uncertainty inherent in the clinical development and regulatory process, the extent and duration of the impact of the COVID-19 pandemic and the other risks described in the Risk Factors section of AGTC's most recent filed annual report on Form 10-K and other periodic reports filed with the SEC. AGTC undertakes no obligation to update any forward-looking statements after the date of this call.

由於許多重要因素，包括臨床開發和監管過程中固有的不確定性、COVID-19 大流行的影響程度和持續時間以及其他風險，實際結果可能與這些前瞻性陳述中討論的結果存在重大差異在 AGTC 最近提交的 10-K 表格年度報告和向美國證券交易委員會提交的其他定期報告的風險因素部分中有所描述。 AGTC 不承擔在本次電話會議之後更新任何前瞻性陳述的義務。

For introductions and opening remarks, I'd like to turn the call over to Sue Washer, Chief Executive Officer of AGTC. Please go ahead.

關於介紹和開場白，我想把電話轉給 AGTC 的首席執行官 Sue Washer。請繼續。

Good morning, and thank you all for joining us. With me on today's call are Susan Schneider, our Chief Medical Officer; and Jon Lieber, our Chief Financial Officer.

早上好，感謝大家加入我們。我們的首席醫療官 Susan Schneider 和我一起參加了今天的電話會議；和我們的首席財務官 Jon Lieber。

During today's call, I'll review our recent accomplishments before Susan reviews the recently reported data from the achromatopsia B3 trial. She will then discuss our plans for reporting data from the X-linked retinitis pigmentosa, or XLRP, Phase II Skyline trial and provide guidance on how we intend to measure this trial's success. Jon will provide an update on the build-out of our manufacturing facility, review our financial results for the second quarter of fiscal year 2022 and discuss our upcoming milestones. After our prepared remarks, we'll take your questions.

在今天的電話會議中，我將先回顧一下我們最近取得的成就，然後 Susan 回顧最近報告的全色盲 B3 試驗數據。然後，她將討論我們報告 X 連鎖視網膜色素變性（XLRP）II 期 Skyline 試驗數據的計劃，並就我們打算如何衡量該試驗的成功提供指導。 Jon 將提供我們製造工廠擴建的最新情況，審查我們 2022 財年第二季度的財務業績，並討論我們即將到來的里程碑。在我們準備好的評論之後，我們將回答您的問題。

In the second quarter, we made significant progress in our lead clinical programs and met important business objectives. Key accomplishments in our XLRP program included reporting additional data from the ongoing Phase I/II clinical trial of AGTC-501, our XLRP gene therapy candidate; and completing enrollment in the Skyline trial.

在第二季度，我們在領先的臨床項目方面取得了重大進展，並實現了重要的業務目標。我們的 XLRP 計劃的主要成就包括報告正在進行的 AGTC-501（我們的 XLRP 基因治療候選藥物）I/II 期臨床試驗的額外數據；並完成 Skyline 試用的註冊。

Last week, we reported data for the highest-dose pediatric group in our ongoing Phase I/II achromatopsia trials. These data are consistent with the previously reported adult data. Importantly, based on the data generated to date, we intend to advance our AGTC-401, our product candidate for patients with a CNGB3 gene mutation that causes achromatopsia, into the next stage of clinical development, pending feedback from an end-of-Phase II meeting with the U.S. Food and Drug Administration, or FDA, expected in the first half of this year.

上週，我們報告了正在進行的 I/II 期全色盲試驗中最高劑量兒科組的數據。這些數據與之前報導的成人數據一致。重要的是，根據迄今為止生成的數據，我們打算將我們的 AGTC-401（我們針對具有導致全色盲的 CNGB3 基因突變患者的候選產品）推進到臨床開發的下一階段，等待階段結束的反饋II 預計在今年上半年與美國食品和藥物管理局 (FDA) 舉行會議。

With respect to the dose, we believe that the 1.1E+12 vector genome per ml dose, which is the dose Group 5 in the Phase I/II trial, is an appropriate dose to move to the next stage of clinical development. Specifically, 2 pediatric patients in this dose group were responders, based on improvements in visual sensitivity. Therefore, of the 3 adults and 4 children for a total of N equals 7 in that dose group and including the 2 adult responders, 4 patients or greater than 50% are visual sensitivity responders. These patients also had improvements in quality of life as measured by a patient-reported outcome survey, or PRO, developed specifically for patients with achromatopsia.

關於劑量，我們認為每毫升劑量 1.1E+12 載體基因組，即 I/II 期試驗中的第 5 組劑量，是進入下一階段臨床開發的合適劑量。具體而言，根據視覺敏感度的改善，該劑量組中的 2 名兒科患者是反應者。因此，在該劑量組的 3 名成人和 4 名兒童中，總共 N 等於 7，包括 2 名成人反應者，4 名患者或大於 50% 的患者是視覺敏感反應者。根據專為全色盲患者開發的患者報告結果調查 (PRO) 衡量，這些患者的生活質量也有所改善。

During the quarter, we also added several talented individuals to our leadership team in order to support advancement of our clinical and preclinical programs. We welcome Hope D'Oyley-Gay as General Counsel; and Dr. Abraham Scaria as Chief Scientific Officer.

在本季度，我們還為我們的領導團隊增加了幾位有才華的人，以支持我們臨床和臨床前項目的推進。我們歡迎 Hope D'Oyley-Gay 擔任總法律顧問； Abraham Scaria 博士擔任首席科學官。

Hope has more than 25 years of legal experience, with the majority of her career set in the health care industry and deep knowledge of pharmaceutical, gene therapy and life science companies.

Hope 擁有超過 25 年的法律經驗，其職業生涯的大部分時間都在醫療保健行業，並且對製藥、基因治療和生命科學公司有著深入的了解。

Abraham also has more than 25 years of experience in the biotech and pharmaceutical industries with extensive knowledge in discovery, research and early stage development and a focus on gene therapies to treat rare diseases. Most recently, he was the Senior Vice President and Chief Scientific Officer of IVERIC Bio, where he was responsible for preclinical research and development for retinal disease therapies.

亞伯拉罕還在生物技術和製藥行業擁有超過 25 年的經驗，在發現、研究和早期開發方面擁有廣泛的知識，並專注於治療罕見疾病的基因療法。最近，他擔任 IVERIC Bio 的高級副總裁兼首席科學官，負責視網膜疾病治療的臨床前研究和開發。

Having recently welcomed Jon and Sue, who are participating in the call today; and Janet Rae, our Senior Vice President of Regulatory and Quality, the appointments of Hope and Abraham complete the newly expanded management team that has both the expertise and passion to continue developing our clinical programs and preclinical pipeline.

最近歡迎參加今天電話會議的 Jon 和 Sue；和我們的監管和質量高級副總裁 Janet Rae，Hope 和 Abraham 的任命完善了新擴大的管理團隊，該團隊擁有繼續開發我們的臨床項目和臨床前管道的專業知識和熱情。

We also appointed James Robinson, President and Chief Executive Officer of Urovant Sciences, to our Board of Directors. James has nearly 3 decades of experience in the biopharmaceutical industry and has successfully led commercial operations at multiple companies. His insights will be invaluable as we move toward late-stage development and commercialization of our lead clinical programs.

我們還任命了 Urovant Sciences 總裁兼首席執行官 James Robinson 為我們的董事會成員。 James 在生物製藥行業擁有近 3 年的經驗，並成功領導了多家公司的商業運營。隨著我們向領先臨床項目的後期開發和商業化邁進，他的見解將是無價的。

The combination of our expanding body of clinical data supporting the potential of our XLRP and achromatopsia B3 candidates and our seasoned and dedicated leadership further increases confidence in our ability to develop transformative gene therapies for patients that currently have no alternative treatment options.

我們不斷擴大的臨床數據體系支持我們的 XLRP 和全色盲 B3 候選人的潛力，加上我們經驗豐富、敬業的領導層，進一步增強了我們為目前沒有其他治療選擇的患者開發轉化基因療法的能力的信心。

I'll now turn the call over to Susan for a discussion of our XLRP and achromatopsia B3 clinical programs.

我現在將電話轉給 Susan，討論我們的 XLRP 和色盲 B3 臨床項目。

Thank you, Sue. First, I will briefly review the data presented last week from our ongoing Phase I/II clinical trials of AGTC-401 for achromatopsia due to mutations in the CNGB3 gene, and AGTC-402 for achromatopsia due to mutations in the CNGA3 gene.

謝謝你，蘇。首先，我將簡要回顧上週我們正在進行的 AGTC-401 治療因 CNGB3 基因突變導致的色盲和 AGTC-402 治療因 CNGA3 基因突變導致的色盲的 I/II 期臨床試驗的數據。

As Sue noted, in both achromatopsia clinical studies, we continue to observe a well-tolerated safety profile in all adults through the full 100-fold dose range with no dose-limiting toxicities. In pediatric patients, both achromatopsia product candidates show a similar well-tolerated safety profile as in adults, except at the very highest dose, the 3.1E+12 vector genomes per mL dose group, where there was significant inflammation resulting in one suspected, unexpected serious adverse reaction, or SUSAR, for AGTC-401; and 2 SUSARs for AGTC-402, all previously reported. Each of these patients have responded well to an adjusted steroid regimen with intraocular inflammation resolved for 2 patients and significantly improved in the third.

正如 Sue 指出的那樣，在兩項全色盲臨床研究中，我們繼續觀察到所有成年人在整個 100 倍劑量範圍內的耐受性良好的安全性，沒有劑量限制性毒性。在兒科患者中，兩種色盲候選產品都顯示出與成人相似的耐受性良好的安全性，除了最高劑量，即每毫升 3.1E+12 個載體基因組的劑量組，該劑量組有明顯的炎症，導致一種可疑的、意外的AGTC-401 的嚴重不良反應或 SUSAR；和 2 個用於 AGTC-402 的 SUSAR，均已報告。這些患者中的每一個都對調整後的類固醇治療方案反應良好，其中 2 名患者的眼內炎症得到解決，而第 3 名患者的眼內炎症得到顯著改善。

Importantly, at the second-highest dose, the 1.1E+12 vector genomes per mL dose, or Group 5 dose, no SUSARs, endophthalmitis or drug-related serious adverse events have been reported in either the pediatric or the adult patients, many of whom are past the 12-month time point. This generally safe and well-tolerated profile is also consistent with earlier data out to as long as 24 months for the AGTC-501, our XLRP product candidate.

重要的是，在第二高劑量下，即每毫升劑量 1.1E+12 載體基因組或第 5 組劑量，在兒科或成人患者中均未報告 SUSAR、眼內炎或藥物相關的嚴重不良事件，其中許多誰超過了 12 個月的時間點。這種普遍安全且耐受性良好的配置文件也與我們的 XLRP 候選產品 AGTC-501 長達 24 個月的早期數據一致。

Of note, in our AGTC-401 clinical trial, we have observed several adult responders out to 12 months based on visual sensitivity, light discomfort and a quality of life questionnaire designed specifically to assess light sensitivity that impacts achromatopsia patients. The most consistent responses are in dose Group 5, which is a dose of 1.1E+12 vector genomes per mL. Importantly, for the AGTC-401 pediatric patients, we also saw responders for visual sensitivity at this dose. For responders, the improvement in visual sensitivity was robust and durable in both adult and pediatric patients.

值得注意的是，在我們的 AGTC-401 臨床試驗中，我們根據視覺敏感度、光不適感和專門設計用於評估影響全色盲患者的光敏感性的生活質量調查表，觀察了幾名成年反應者長達 12 個月。最一致的反應出現在第 5 組劑量中，該劑量為每毫升 1.1E+12 個載體基因組。重要的是，對於 AGTC-401 兒科患者，我們還看到了該劑量下視覺敏感度的反應者。對於反應者，視覺敏感度的改善在成人和兒童患者中都是穩健和持久的。

Interestingly, this is also the dose with the best response in our XLRP clinical trial. This slide focuses on the 7 Group 5 patients. Importantly, 4 of the 5 patients in Group 5 who were able to complete the perimetry testing, 2 adults and 2 children, had robust and durable responses; and several had improvements in one or more additional endpoints, including a measure of quality of life. We also observed that the 2 very young children, both 5 years of age, who were unable to complete the visual sensitivity test, had improvements in their quality of life survey and one of them had improvements in best corrected visual acuity, or BCVA.

有趣的是，這也是我們 XLRP 臨床試驗中反應最好的劑量。這張幻燈片重點介紹了第 5 組的 7 名患者。重要的是，第 5 組中 5 名能夠完成視野檢查的患者中有 4 名（2 名成人和 2 名兒童）具有強烈而持久的反應；有幾個在一個或多個額外的終點上有所改善，包括生活質量的衡量標準。我們還觀察到，2 名年幼的兒童（均為 5 歲）無法完成視覺敏感度測試，但他們的生活質量調查有所改善，其中一名兒童的最佳矯正視力 (BCVA) 有所改善。

Here, you can see the visual sensitivity data as graphs over time for the 2 adult and 2 pediatric responders in Group 5 that illustrate durable and robust improvements. In the graph on the left, the 4 responders averaged a 6-decibel improvement in mean visual sensitivity compared to baseline, which represents a 16- to 24-fold increase versus the contralateral untreated eyes that showed relatively little change over time. The graph on the right shows an even larger improvement in those responders that also met the hurdle of 5 loci increasing by 7 decibels.

在這裡，您可以看到第 5 組中 2 名成人和 2 名兒童響應者隨時間變化的視覺敏感度數據圖表，這些數據說明了持久而穩健的改進。在左圖中，與基線相比，4 名反應者的平均視覺敏感度平均提高了 6 分貝，這表示與對側未治療的眼睛相比，增加了 16 到 24 倍，後者隨時間變化相對較小。右圖顯示，那些也滿足 5 個位點增加 7 分貝障礙的響應者的改善更大。

Based on these data, we believe that AGTC-401 has best-in-class potential for the treatment of achromatopsia B3, and we look forward to sharing information in the first half of this year on the next steps in clinical development following our end of Phase II meeting with the FDA.

基於這些數據，我們相信 AGTC-401 在治療全色盲 B3 方面具有一流的潛力，我們期待在今年上半年分享有關臨床開發後續步驟的信息。與 FDA 的第二階段會議。

Let's now shift our focus to our XLRP clinical program. As Sue mentioned, we reported additional data from the ongoing XLRP Phase I/II trial in the second quarter of calendar year 2021. Consistent with previously reported data, these additional results demonstrated a 50% response rate for Groups 5 and 6. Based on microperimetry assessments and with best corrected visual acuity outcomes, we continue to show evidence of a biological response at month 12.

現在讓我們將注意力轉移到我們的 XLRP 臨床項目上。正如 Sue 提到的，我們在 2021 日曆年第二季度報告了正在進行的 XLRP I/II 期試驗的額外數據。與之前報告的數據一致，這些額外結果表明第 5 組和第 6 組的響應率為 50%。基於微視野測量評估和最佳矯正視力結果，我們在第 12 個月繼續顯示生物反應的證據。

Improvements in visual sensitivity also correlate with improvements in retinal structure. Furthermore, we are seeing evidence of a continued durability of response up to 24 months after treatment based on data from a subset of patients in the Phase I/II trial who have reached this time point. These data reinforce our belief that AGTC-501 is a differentiated product candidate with best-in-class potential, and we look forward to reporting the full 2-year data later in calendar year 2022.

視覺敏感度的改善也與視網膜結構的改善相關。此外，根據 I/II 期試驗中已達到該時間點的部分患者的數據，我們看到了治療後長達 24 個月的持續反應持久性的證據。這些數據強化了我們的信念，即 AGTC-501 是具有同類最佳潛力的差異化候選產品，我們期待在 2022 年晚些時候報告完整的 2 年數據。

As announced last month, we completed enrollment in the Skyline trial. We exceeded the enrollment target for this trial, which we believe reflects the strong interest in our XLRP candidate among patients and physicians. As many of you are aware, Skyline is a multisite, masked Phase II expansion of the ongoing Phase I study in which patients are randomized to either a high or low dose of AGTC-501, with the primary objective to identify the proportion of treated eyes that demonstrate improvement from baseline in measures of visual sensitivity and visual acuity, as well as the patient's ability to navigate a mobility maze with changing obstacles and under varying light conditions.

正如上個月宣布的那樣，我們完成了 Skyline 試驗的註冊。我們超出了該試驗的入組目標，我們認為這反映了患者和醫生對我們的 XLRP 候選人的濃厚興趣。正如你們中的許多人所知，Skyline 是正在進行的 I 期研究的多站點、掩蔽的 II 期擴展，在該研究中，患者被隨機分配到高劑量或低劑量的 AGTC-501，主要目的是確定接受治療的眼睛的比例這表明視覺靈敏度和視敏度的測量值比基線有所改善，以及患者在不斷變化的障礙物和不同光照條件下導航移動迷宮的能力。

Importantly, this is our first clinical trial that has the potential to demonstrate a correlation between visual sensitivity and/or visual acuity with maze outcomes, a new functional endpoint also added to the Vista Phase II/III clinical trial. Skyline and Vista use the same inclusion and exclusion criteria, which are based on baseline characteristics identified in the Phase I/II clinical trial utilized to predict responders.

重要的是，這是我們的第一個臨床試驗，有可能證明視覺靈敏度和/或視力與迷宮結果之間存在相關性，這是 Vista II/III 期臨床試驗中還添加了一個新的功能終點。 Skyline 和 Vista 使用相同的納入和排除標準，這些標準基於用於預測反應者的 I/II 期臨床試驗中確定的基線特徵。

We are on track to report interim masked 3-month data from Skyline in the second quarter of calendar year 2022. And today, I will provide guidance on our expectation for these data and review key clinical assessments performed in this clinical trial. Anticipated key takeaways for the Skyline month 3 interim analysis are summarized here.

我們有望在 2022 日曆年第二季度報告來自 Skyline 的中期掩蔽 3 個月數據。今天，我將就我們對這些數據的預期提供指導，並審查在該臨床試驗中進行的關鍵臨床評估。此處總結了 Skyline 第 3 個月中期分析的預期要點。

Based on the body of safety data from our Phase I/II clinical trial, we have confidence that Skyline safety outcomes will continue to show that our XLRP candidate is generally safe and well tolerated. We also plan to report on the proportion of patients showing improvement in visual sensitivity in their treated eye.

根據我們 I/II 期臨床試驗的大量安全數據，我們相信 Skyline 的安全結果將繼續表明我們的 XLRP 候選人通常是安全且耐受性良好的。我們還計劃報告接受治療的眼睛視覺敏感度改善的患者比例。

Based on the data cutoff time point for this interim analysis, we intend to evaluate data from the first 13 of a total of 14 patients enrolled in the Skyline trial. Data to date from the Phase I/II trial have demonstrated a 50% response rate in higher-dose groups when including patients who meet the entry criteria for the Skyline and Vista trials, and the Vista trial is powered to show a statistically significant difference at a 50% response rate.

根據該中期分析的數據截止時間點，我們打算評估 Skyline 試驗中登記的總共 14 名患者中前 13 名的數據。迄今為止，I/II 期試驗的數據表明，當包括符合 Skyline 和 Vista 試驗進入標準的患者時，高劑量組的反應率為 50%，而 Vista 試驗有能力顯示統計學上的顯著差異50% 的響應率。

I want to emphasize that at the time we present the 3-month Skyline data, the trial will be masked. This means that while we will be able to report on responders in 2 groups, we will not know the specific dose group assignments. Outcomes will be reported only as dose group A and dose group B. We also expect that best corrected visual acuity will continue to show supportive evidence of a biological response with a difference between each patient's treated versus untreated eye. We plan to present these data as the number of eyes in dose group A and in dose group B with improvement over baseline of 5 ETDRS letters or more compared to the untreated eye. We consider this to be a response to treatment.

我想強調的是，在我們提供 3 個月的 Skyline 數據時，試驗將被掩蓋。這意味著雖然我們能夠報告 2 組的反應者，但我們不知道具體的劑量組分配。結果將僅報告為劑量組 A 和劑量組 B。我們還預計最佳矯正視力將繼續顯示生物反應的支持證據，每個患者的治療眼與未治療眼之間存在差異。我們計劃將這些數據呈現為劑量組 A 和劑量組 B 中與未治療的眼睛相比基線改善 5 個 ETDRS 字母或更多的眼睛數量。我們認為這是對治療的反應。

While we have previously reported visual sensitivity and visual acuity data, the Skyline trial is the first that utilizes a visual navigation challenge, or VNC, which is a mobility maze used to assess functional vision. We believe that improvements in maze performance have the potential to correlate with improvements in visual sensitivity and/or visual acuity.

雖然我們之前報告過視覺敏感度和視敏度數據，但 Skyline 試驗是第一個利用視覺導航挑戰或 VNC 的試驗，VNC 是一種用於評估功能視覺的移動迷宮。我們認為，迷宮性能的改進有可能與視覺靈敏度和/或視敏度的改進相關聯。

Finally, while we are assessing changes in macular structure in the Skyline trial, we do not believe, based on data from the Phase I/II study, that we will see any consistent changes in structure at the 3-month interim analysis as this time point is too early to capture these changes. If the 3-month interim data achieve these expectations, we believe we will have significantly derisked the Vista clinical trial, which, together with data from both the Phase I/II study and the Skyline Phase II expansion study, is intended to support a BLA filing.

最後，雖然我們在 Skyline 試驗中評估黃斑結構的變化，但我們認為，根據 I/II 期研究的數據，我們不會像這次那樣在 3 個月的中期分析中看到任何一致的結構變化現在捕捉這些變化還為時過早。如果 3 個月的中期數據達到這些預期，我們認為我們將大大降低 Vista 臨床試驗的風險，該試驗與 I/II 期研究和 Skyline II 期擴展研究的數據一起，旨在支持 BLA備案。

I'd now like to briefly review the key Skyline efficacy endpoints. To start, we can look at vision and function in 2 ways: Visual function and functional vision. Visual function describes how well the eyes and basic visual system can detect a target stimulus. In other words, how information is transmitted through the eye to the brain. Microperimetry and best corrected visual acuity are tests used to assess visual function. We are utilizing macular integrity assessment system, or MAIA microperimetry, to measure light sensitivity of the retina in the Skyline and Vista trials as we believe it can appropriately measure functional changes of visual sensitivity to treatment in XLRP patients.

我現在想簡要回顧一下關鍵的 Skyline 療效終點。首先，我們可以通過兩種方式來看待視覺和功能：視覺功能和功能視覺。視覺功能描述了眼睛和基本視覺系統檢測目標刺激的能力。換句話說，信息是如何通過眼睛傳遞到大腦的。顯微視野計和最佳矯正視力是用於評估視覺功能的測試。我們正在利用黃斑完整性評估系統或 MAIA 微視野測量法來測量 Skyline 和 Vista 試驗中視網膜的光敏感性，因為我們相信它可以適當地測量 XLRP 患者視覺敏感性對治療的功能變化。

Functional vision refers to how well a patient performs while interacting with the visual environment. That is how the brain processes information to perform tasks of daily living. The mobility maze, which is a new endpoint for the AGTC-501 clinical program, assesses functional vision.

功能性視覺是指患者在與視覺環境互動時的表現。這就是大腦處理信息以執行日常生活任務的方式。移動迷宮是 AGTC-501 臨床項目的新終點，用於評估功能性視覺。

These are the key ways we plan on evaluating outcomes for Skyline to potentially show a positive response to treatment in a clinically meaningful way and with endpoints that can support registration. We also believe that it is important to show structure-function relationships in support of a treatment effect.

這些是我們計劃評估 Skyline 結果的關鍵方法，以可能以具有臨床意義的方式和可以支持註冊的終點顯示對治療的積極反應。我們還認為，顯示支持治療效果的結構-功能關係很重要。

Ellipsoid zone, or EZ width, is used to assess changes in macular structure. As we have previously discussed, EZ degeneration and loss over time is a hallmark of XLRP, and we've shared data from the Phase I/II trial demonstrating a significant association between improvements in visual sensitivity, measured by MAIA; and improvements in retinal health, measured by improvement in EZ, in Groups' 4 to 6. However, since EZ changes occur more slowly than changes in visual sensitivity or visual acuity, we do not expect to see evidence of structural improvements in the 3-month Skyline interim analysis.

橢球區或 EZ 寬度用於評估黃斑結構的變化。正如我們之前所討論的，隨著時間的推移，EZ 退化和丟失是 XLRP 的一個標誌，我們已經共享了 I/II 期試驗的數據，證明了通過 MAIA 測量的視覺靈敏度的改善之間存在顯著關聯；在第 4 至 6 組中，通過 EZ 的改善來衡量視網膜健康的改善。但是，由於 EZ 的變化比視覺敏感度或視力的變化發生得更慢，我們預計不會看到 3- 結構改善的證據月 Skyline 中期分析。

The mobility maze is a new endpoint for the AGTC-501 clinical program. A mobility maze was validated as an endpoint for the approval of Luxturna, the first gene therapy approved for inherited retinal disease. Therefore, there is regulatory precedent for this measurement as a clinically meaningful and accepted endpoint for registration.

移動迷宮是 AGTC-501 臨床項目的新終點。移動迷宮被驗證為批准 Luxturna 的終點，Luxturna 是第一個被批准用於遺傳性視網膜疾病的基因療法。因此，該測量作為具有臨床意義且可接受的註冊終點存在監管先例。

We are using the Ora visual navigation challenge or VNC. This slide shows an example of the type of outputs and data that will be evaluated using the maze and how we currently plan to report the outcomes for the Skyline 3-month interim analysis. The Ora-VNC has multiple possible configurations that create varying levels of challenge conditions with respect to maze path and obstacles. In addition, patients are tested over a range of lighting conditions from dim to bright interior light. Patient performance is assessed by both the time taken to traverse the maze as well as accuracy in navigating the course and avoiding obstacles.

我們正在使用 Ora 視覺導航挑戰或 VNC。這張幻燈片顯示了將使用迷宮評估的輸出和數據類型的示例，以及我們目前計劃如何報告 Skyline 3 個月期中分析的結果。 Ora-VNC 具有多種可能的配置，可針對迷宮路徑和障礙物創建不同級別的挑戰條件。此外，在從昏暗到明亮的室內光線的一系列照明條件下對患者進行測試。通過穿越迷宮所需的時間以及導航路線和避開障礙物的準確性來評估患者的表現。

To pass at a given light level, the patient must navigate the maze within both a defined time and accuracy rate. The ability to pass the maze challenge at lower light levels is consistent with the response to treatment. The FDA has previously provided feedback to us that it considers a clinically meaningful change to be a patient's ability to pass the test in 2 illumination levels lower than baseline. A key benefit to the mobility maze is that it has the potential to capture improvements in multiple functional endpoints as the ability to successfully navigate the maze is a function of both visual sensitivity and visual acuity.

要在給定的光照水平下通過，患者必須在規定的時間和準確率內通過迷宮。在較低光照水平下通過迷宮挑戰的能力與對治療的反應一致。 FDA 之前向我們提供了反饋，它認為具有臨床意義的變化是患者能夠在低於基線的 2 個照明水平下通過測試。移動迷宮的一個關鍵好處是它有可能捕獲多個功能端點的改進，因為成功導航迷宮的能力是視覺靈敏度和視覺敏銳度的函數。

In addition to assessing the Ora-VNC results for efficacy, we plan to also evaluate potential correlations between changes in mobility maze scores and improvements in microperimetry and best corrected visual acuity assessments in the Skyline 3-month interim analysis.

除了評估 Ora-VNC 結果的有效性外，我們還計劃在 Skyline 3 個月中期分析中評估移動迷宮分數的變化與顯微視野計和最佳矯正視力評估之間的潛在相關性。

Now let's turn our attention to the XLRP Vista clinical trial. This slide summarizes the Vista study design. As previously discussed, Vista is a Phase II/III trial with 2 treatment arms that correspond to the doses used in Groups 2 and 5 in the Phase I/II trial as well as an untreated control group. The primary endpoint is improvement in visual sensitivity based on the percent of responder patients.

現在讓我們將注意力轉移到XLRP Vista 臨床試驗上。這張幻燈片總結了 Vista 研究設計。如前所述，Vista 是一項 II/III 期試驗，有 2 個治療組，對應於 I/II 期試驗中第 2 組和第 5 組使用的劑量以及未治療的對照組。主要終點是基於響應患者百分比的視覺靈敏度改善。

A responder is a patient that has at least 5 predefined loci improved by at least 7 decibels. However, as we have stated previously, we believe that, given this is an orphan indication, that an approval will likely be based on the totality of the data, including the mean improvement in visual sensitivity over the entire treated area, supportive improvements in visual acuity and structure, a favorable risk/benefit profile and improvement in patient reported outcomes or PROs.

響應者是至少有 5 個預定義位點改善至少 7 分貝的患者。然而，正如我們之前所說，我們認為，鑑於這是一個孤兒適應症，批准可能會基於數據的整體性，包括整個治療區域視覺敏感度的平均改善、視覺的支持性改善敏銳度和結構、有利的風險/收益概況以及患者報告的結果或 PRO 的改善。

At the time of the first Vista interim analysis, we expect to have 12-month Skyline data and 24-month data from the Phase I/II clinical trial, which will enable us to have a robust data package to review. We believe that AGTC-501 has best-in-class potential for the treatment of XLRP, and look forward to sharing additional data from all 3 clinical trials with you in the months ahead.

在第一次 Vista 中期分析時，我們預計會有 12 個月的 Skyline 數據和來自 I/II 期臨床試驗的 24 個月數據，這將使我們能夠擁有一個強大的數據包來審查。我們相信 AGTC-501 具有一流的 XLRP 治療潛力，並期待在未來幾個月與您分享所有 3 項臨床試驗的更多數據。

In summary, we have generated a significant body of clinical and preclinical data to date. While these data are important to the development of our achromatopsia and XLRP product candidates, they also provide further evidence that our preclinical approach to product development and our technology platform are robust and supportive of our broader portfolio of gene therapy candidates.

總之，迄今為止，我們已經生成了大量臨床和臨床前數據。雖然這些數據對我們色盲和 XLRP 候選產品的開發很重要，但它們也提供了進一步的證據，證明我們的臨床前產品開發方法和我們的技術平台是強大的，並支持我們更廣泛的基因治療候選產品組合。

I'll now turn the call over to Jon for a brief update on our manufacturing facility and review of second quarter 2022 financial results.

我現在將電話轉給喬恩，簡要介紹我們的製造工廠的最新情況，並回顧 2022 年第二季度的財務業績。

Thanks, Susan. I'll first provide an update on the construction progress of our manufacturing facility, followed by a summary of our financial results and near-term milestones.

謝謝，蘇珊。我將首先提供有關我們製造工廠建設進度的最新信息，然後是我們的財務業績和近期里程碑的摘要。

Construction of our new leased manufacturing and quality control facility is in process, with initial operations at the facility expected to begin in the fourth quarter of calendar year 2022. The facility is a key part of our strategy to expedite the potential BLA filing and commercial launch, subject to FDA approval, of AGTC-501 for the treatment of XLRP; and support the manufacturing and supply of materials for AGTC-401 and our early pipeline programs. As seen here, the facility is well underway.

我們新的租賃製造和質量控制設施的建設正在進行中，該設施的初始運營預計將於 2022 日曆年第四季度開始。該設施是我們加快潛在 BLA 備案和商業啟動戰略的關鍵部分，經 FDA 批准，AGTC-501 用於治療 XLRP；支持 AGTC-401 和我們早期管道項目的材料製造和供應。如圖所示，該設施正在順利進行中。

Now I'll turn to our financial results. Net loss for the 3 and 6 months ended December 31, 2021, was $19.1 million and $36.3 million, respectively, compared to $15.5 million and $30.8 million, respectively, during the comparable 2020 periods. As of December 31, 2021, we had cash, cash equivalents and investments of $72.8 million. We believe these funds will be sufficient to allow us to generate data from our ongoing and planned clinical programs and fund currently planned research and discovery programs into calendar year 2023.

現在我將談談我們的財務業績。截至 2021 年 12 月 31 日的第 3 個月和第 6 個月的淨虧損分別為 1910 萬美元和 3630 萬美元，而 2020 年同期的淨虧損分別為 1550 萬美元和 3080 萬美元。截至 2021 年 12 月 31 日，我們擁有現金、現金等價物和投資 7280 萬美元。我們相信這些資金將足以讓我們從正在進行的和計劃中的臨床項目中生成數據，並為目前計劃中的研究和發現項目提供資金，直至 2023 年。

Importantly, as you will see on the next slide, we have multiple upgoing milestones, which we believe have substantial potential for creating significant value for patients and shareholders. This is a milestone-rich time for AGTC that includes multiple clinical data readouts and additional preclinical milestones. These include reporting the Skyline 3-month interim data in the second quarter of this year and 12-month Skyline and interim Vista trial results in the first half of calendar year 2023.

重要的是，正如您將在下一張幻燈片中看到的那樣，我們有多個里程碑，我們相信這些里程碑具有為患者和股東創造重大價值的巨大潛力。對於 AGTC 來說，這是一個充滿里程碑的時刻，包括多個臨床數據讀數和其他臨床前里程碑。其中包括報告今年第二季度的 Skyline 3 個月中期數據以及 2023 日曆年上半年的 12 個月 Skyline 和中期 Vista 試驗結果。

In our achromatopsia B3 program, we reported the 3-month pediatric data from both trials last week and expect to report end of Phase II feedback from the FDA in the first half of 2022. We also expect to continue advancing our earlier stage and partner programs, which provide significant pipeline potential across multiple disease indications with unmet medical needs.

在我們的全色盲 B3 計劃中，我們上週報告了兩項試驗的 3 個月兒科數據，並預計將在 2022 年上半年報告來自 FDA 的 II 期結束反饋。我們還預計將繼續推進我們的早期階段和合作夥伴計劃，這為未滿足醫療需求的多種疾病適應症提供了巨大的管道潛力。

That concludes our remarks today. Operator, you may now open the line for our question-and-answer period.

我們今天的發言到此結束。接線員，您現在可以打開我們的問答環節了。

(Operator Instructions) Our first questions come from the line of Joe Pantginis with H.C. Wainwright.

（操作員說明）我們的第一個問題來自 Joe Pantginis 和 H.C.溫賴特。

A couple of questions, if you don't mind. So first, I guess, Jon, based on your manufacturing facility comments, I mean, the company has always been doing a lot of early preparations regarding manufacturing and having things in-house. I guess with all the management that you've just brought in, how should we view the company's growth with regard to future hirings and employees for the manufacturing facility as well?

幾個問題，如果你不介意的話。所以首先，我想，喬恩，根據你對製造工廠的評論，我的意思是，公司一直在做很多關於製造和內部生產的早期準備工作。我想對於您剛剛帶來的所有管理層，我們應該如何看待公司在未來招聘和製造工廠員工方面的增長？

Yes. That's a good question, Joe. Thank you for joining us this morning and thanks for the question. So I would say we don't -- we certainly don't provide specific guidance on headcount, et cetera. But we had a lot of hiring in the back half of last -- of the last calendar year 2021. And our hiring for the manufacturing facility for this year going forward is going to be focused on, obviously, folks who can help get the facility ready to be GMP-certified. And then ultimately, a focus on people who then can operate -- the operators who will work inside the facility to actually start making the materials.

是的。這是個好問題，喬。感謝您今天早上加入我們並感謝您提出問題。所以我想說我們不會——我們當然不會提供關於員工人數等方面的具體指導。但是我們在上個日曆年 2021 年的下半年招聘了很多人。很明顯，我們今年對製造工廠的招聘將集中在可以幫助獲得該設施的人身上準備好通過 GMP 認證。然後最終，關注那些可以操作的人——將在設施內工作以實際開始製造材料的操作員。

So I think we should be thinking about more hiring this year at a slower pace than perhaps it was last year. But again, all of that is factored into our cash runway that we've given as to the time.

因此，我認為我們應該考慮以比去年更慢的速度招聘更多人。但同樣，所有這些都考慮到了我們給出的時間的現金跑道。

Absolutely. That's helpful. And then I guess, just sort of going back to the expectations around Skyline. Sue, I'm hoping you can either remind us and/or give a little color with regard to the maze challenge. Obviously, the endpoints are pretty laid out there as you did it. I guess the question that I have is maybe a little more color around the time points that you're testing. And is it a different configuration at each time point? You talk about multiple configurations at each time point. So hopefully getting a little more color there.

絕對地。這很有幫助。然後我想，只是回到了對 Skyline 的期望。蘇，我希望你能提醒我們和/或給我們一些關於迷宮挑戰的顏色。顯然，端點的佈局與您所做的一樣。我想我的問題可能是您正在測試的時間點周圍有更多顏色。是不是每個時間點的配置都不一樣？您在每個時間點談論多種配置。所以希望那裡有更多的顏色。

Joe, thank you for that question. And actually, I'm going to let Susan address this. She has all of the information on the maze in her head and so we'll let her give you that color. Susan?

喬，謝謝你提出這個問題。實際上，我要讓 Susan 解決這個問題。她腦子裡有關於迷宮的所有信息，所以我們會讓她給你那種顏色。蘇珊？

Thank you, Sue. So the maze that we're utilizing by Ora actually is standardized and developed with keeping in mind that patients won't be able to learn the course in subsequent utilization of the course. It actually uses 4 different courses with varying levels of difficulty, navigation capabilities, et cetera, and really focusing on low-contrast visual navigation challenge as well as high-contrast visual navigation challenge.

謝謝你，蘇。因此，我們 Ora 使用的迷宮實際上是標準化和開發的，同時牢記患者將無法在後續使用該課程時學習該課程。它實際上使用了 4 個不同的課程，難度、導航能力等各不相同，真正專注於低對比度視覺導航挑戰和高對比度視覺導航挑戰。

So hopefully, that answers your question. The patients will be assessed per visit and we'll be assessing the change from baseline as outlined in a pass/fail fashion.

希望這能回答您的問題。每次訪問都會對患者進行評估，我們將按照通過/未通過的方式評估相對於基線的變化。

Yes, that's helpful. I guess maybe just an add on there. Just remind us the frequency of visits.

是的，這很有幫助。我想也許只是在那裡添加。只是提醒我們訪問的頻率。

We're still working through what those are. They will be the same visits as we have for the study itself.

我們仍在努力解決這些問題。他們將與我們為研究本身進行的訪問相同。

Our next question comes from the line of Dae Gon Ha, Stifel.

我們的下一個問題來自 Dae Gon Ha, Stifel 的台詞。

I had 2 related to the studies that are ongoing. So with regards to the XLRP, recognizing a lot of these studies are kind of coming in fast and furious, Sue, I think in our prior conversation, you talked about perhaps approaching the FDA for the Vista endpoint discussion should you try to pursue the mobility maze.

我有 2 個與正在進行的研究有關。所以關於 XLRP，認識到很多這些研究都在快速而激烈地進行，Sue，我想在我們之前的談話中，你談到如果你試圖追求移動性，可能會接近 FDA 進行 Vista 端點討論迷宮。

Today, Susan talked about the totality being important. So how are you kind of currently thinking about approaching the FDA to think about the 2 -- or the primary endpoint designation or switch the primary endpoint designation, if you will? Is there a certain date that you need to kind of approach them by to get to an agreement? Or is it pretty much at any time point?

今天，蘇珊談到整體很重要。那麼，您目前如何考慮聯繫 FDA 來考慮 2 - 或主要終點指定或轉換主要終點指定，如果您願意的話？您是否需要在特定日期之前與他們聯繫以達成協議？或者幾乎在任何時間點？

And then second question, perhaps more for Susan. As we think about the achromatopsia B3 and the Phase II discussion, maybe a housekeeping question. Has that meeting been calendared or penciled in to the calendar?

然後是第二個問題，也許更多是針對蘇珊的。當我們考慮全色盲 B3 和第二階段的討論時，可能是一個內務處理問題。該會議是否已安排或記入日曆？

And two, what are sort of the outcomes, if you want to think about -- or how should we think about the outcomes? Recognizing that go-forward would be good, but what are sort of the scenarios that you guys are contemplating as we anticipate that update?

第二，如果您想考慮什麼結果，或者我們應該如何考慮結果？認識到繼續前進會很好，但是在我們預期更新時你們正在考慮什麼樣的場景？

As far as the XLRP and when we might interact with the FDA, I think it's important to understand, like with a lot of orphan indications and new modalities like gene therapy, we have a wide range of opportunities to have interaction with the FDA in different types of meetings over time. And if we ever see anything that we feel warrants us to have an interaction, we will definitely reach out.

至於 XLRP 以及我們何時可能與 FDA 互動，我認為重要的是要了解，就像許多孤兒適應症和基因治療等新模式一樣，我們有廣泛的機會與 FDA 在不同的地方進行互動隨著時間的推移會議的類型。如果我們看到任何我們認為值得我們進行互動的事情，我們一定會伸出援手。

In a more formal way, what we have signaled and guided to is, at the time we have the interim -- the first interim analysis for Vista, we will also have 12-month data for Skyline and 24-month data for our Phase I/II. So that is 3 sets of data, 3 different sets of patients, very robust information that we'll be able to analyze. And at that time, if there are things that we want to interact with the FDA, we do think that we'll have the body of data to do it. But it will also be a reaction to what the data tells us and what meeting we can take advantage of with the FDA.

以更正式的方式，我們發出的信號和指導是，在我們進行中期 - Vista 的第一次中期分析時，我們還將獲得 Skyline 的 12 個月數據和第一階段的 24 個月數據/二。所以這是 3 組數據，3 組不同的患者，我們將能夠分析的非常可靠的信息。那時，如果有什麼事情我們想與 FDA 互動，我們確實認為我們會有數據主體來做這件事。但這也將是對數據告訴我們的內容以及我們可以利用與 FDA 的會議的反應。

And then I'll pass it off to Susan about the end of Phase II and what various outcomes we might have in that discussion. But we have mentioned before that we do have that meeting on the books. We haven't guided to a specific date, but we have received the meeting. So we're quite confident that we'll be able to provide feedback to the public by the end of June. Susan?

然後我會將第二階段的結束以及我們在該討論中可能產生的各種結果轉交給 Susan。但我們之前已經提到過，我們確實有過那次會議。我們還沒有指導具體日期，但我們已經收到了會議。因此，我們非常有信心能夠在 6 月底之前向公眾提供反饋。蘇珊？

Thank you, Sue. And as you said, we do have a meeting date and we are preparing for that as we speak and are excited to be able to interact with the FDA.

謝謝你，蘇。正如你所說，我們確實有一個會議日期，我們正在為此做準備，並且很高興能夠與 FDA 互動。

Basically, at an end of Phase II meeting, we propose clinical questions that will give us additional guidance on the planned Phase III and the path forward to be able to file and be successful in that light.

基本上，在第二階段會議結束時，我們會提出臨床問題，這些問題將為我們提供有關計劃中的第三階段的額外指導，以及能夠在這方面取得成功的前進道路。

And so the endpoints that we have in the Phase I/II study that showed us a response as well as some additional questions about how we are going to move forward to Phase III, consistent with the study design that we will be proposing, we'll be looking for guidance from the FDA about adequacy of that program.

因此，我們在 I/II 期研究中的終點向我們展示了一個回應以及一些關於我們將如何推進到 III 期的額外問題，與我們將提出的研究設計一致，我們'您將尋求 FDA 關於該計劃的充分性的指導。

And I'll just jump in real quickly. I think that maybe what you were getting to, we were -- we would consider success from the end of Phase II to get to agreement on a protocol. And that may involve a lot of back and forth, it generally does, as the FDA is learning the specifics of our program and our constructs and the data we have and we're learning their intent. And we would expect to have that back and forth and make adjustments. And success is to have a trial that can be executed and go forward, such as what we got out of the end of Phase II interaction with the FDA for our XLRP program.

我會很快投入其中。我認為也許你要達到的目標，我們是——我們會考慮從第二階段結束時的成功，以就協議達成一致。這可能涉及很多來回，通常會這樣，因為 FDA 正在了解我們計劃的細節和我們的結構以及我們擁有的數據，並且我們正在了解他們的意圖。我們希望來回進行調整併進行調整。成功就是有一個可以執行並繼續進行的試驗，比如我們在 XLRP 項目中與 FDA 的第二階段互動結束時得到的結果。

Awesome. Look forward to that second quarter update.

驚人的。期待第二季度的更新。

Our next questions come from the line of Yanan Zhu with Wells Fargo.

我們的下一個問題來自 Yanan Zhu 與 Wells Fargo 的對話。

I have kind of 3 groups of questions for each of the endpoints to be recorded for Skyline. For the visual sensitivity, so first of all, would you mind talking about what is the bar for success in terms of response rate -- responder rate for each of the endpoints? And specifically for the visual sensitivity, would it be a 7/5 analysis or a sensitivity across the retina analysis?

對於要為 Skyline 記錄的每個端點，我有 3 組問題。對於視覺敏感度，首先，您是否介意談談在響應率方面取得成功的標準是什麼——每個端點的響應者率？特別是對於視覺靈敏度，它是 7/5 分析還是整個視網膜分析的靈敏度？

For the BCVA, I think you mentioned 5-letter as the response criteria. Is that one line of improvement above the test, retest threshold for XLRP in this specific indication? And for the VNC, is it a binocular or single eye test? And is the -- are the low-contrast and high-contrast setting going to be reported separately as 2 different responses? Or are they somehow incorporated into 1 response?

對於 BCVA，我想你提到了 5 個字母作為響應標準。在這個特定適應症中，是否有高於 XLRP 測試、再測試閾值的改進？對於 VNC，它是雙眼還是單眼測試？低對比度和高對比度設置是否會作為 2 種不同的響應分別報告？或者它們是否以某種方式合併到 1 個響應中？

Yanan, it's nice to talk to you and address these questions. I'm going to provide an overview and then let Susan provide some more color. So I think that we've had many discussions about visual sensitivity in that the bar set to precedents to older machines and into the glaucoma space for visual sensitivity is the idea of having at least a 7-decibel change in at least 5 loci. And that is the bar for success. We've set that at 50% because that is what we saw in the Phase I/II for that bar.

亞南，很高興與你交談並解決這些問題。我將提供一個概述，然後讓 Susan 提供更多顏色。所以我認為我們已經就視覺敏感度進行了很多討論，因為設置為舊機器先例的酒吧和進入青光眼空間的視覺敏感度是在至少 5 個位點中至少有 7 分貝變化的想法。這就是成功的標準。我們將其設置為 50%，因為這是我們在該欄的第一階段/第二階段中看到的。

But we have always stated that we feel, in a disease where patients are going blind and will be blind, legally blind in their 40s and totally blind probably in their 60s, that we think it's the totality of data. And so we'll report that visual sensitivity as the mean over the entire area. Because we think that is what patients care about, is what is the improvement they see in their vision over the entire area, especially as in a normal situation, their vision would just be declining.

但我們一直表示，我們認為，在一種疾病中，患者正在失明並且將失明，在 40 多歲時合法失明，可能在 60 多歲時完全失明，我們認為這是數據的全部。因此，我們會將視覺敏感度報告為整個區域的平均值。因為我們認為患者關心的是他們在整個區域看到的視力改善情況，尤其是在正常情況下，他們的視力只會下降。

For BCVA, it is not the primary endpoint, it's a secondary endpoint. And we feel, again, that in an indication where they're losing vision every day and will become completely blind, that an improvement of 5 letters is meaningful to them. That is what we saw in a statistically significant way in the Phase I/II. So meeting the same criteria that we saw in the Phase I/II for visual sensitivity in BCVA would what we -- would be what we consider successful.

對於 BCVA，它不是主要終點，而是次要終點。我們再次感到，在他們每天都在失去視力並將變得完全失明的跡像中，5 個字母的改善對他們來說是有意義的。這就是我們在第一階段/第二階段以具有統計意義的方式看到的。因此，滿足我們在 BCVA 的 I/II 階段中看到的相同視覺敏感度標準將是我們認為成功的。

On the maze, I'll just provide an overview. In the maze, I'd really like Susan to provide some more data. But we will be testing each eye, so each eye separately, to be able to show the treated eye versus the untreated eye. And we are testing in both of those contrast situations.

關於迷宮，我只是提供一個概覽。在迷宮中，我真的希望 Susan 提供更多數據。但是我們將測試每隻眼睛，所以每隻眼睛都是分開的，以便能夠顯示經過治療的眼睛與未經治療的眼睛。我們正在這兩種對比情況下進行測試。

And I'll let Susan speak to more of the details of the assessment and reporting on that.

我會讓 Susan 談談評估和報告的更多細節。

Thank you, Sue. And just going back to the BCVA, what we consider as a response is change from baseline in 5 letters or more. That puts us outside of the level of noise. Again, as Sue said, that is supportive data for the primary endpoint. The BCVA will not be the primary endpoint for us.

謝謝你，蘇。回到 BCVA，我們認為響應是相對於基線有 5 個或更多字母的變化。這使我們處於噪音水平之外。同樣，正如 Sue 所說，這是主要終點的支持數據。 BCVA 不會是我們的主要終點。

With respect to the microperimetry, we are using the macular integrity assessment system, or MAIA, which is a standardized way of measuring light sensitivity of the retina. We're looking at central sensitivity. And as she said, the FDA has suggested that we should have a minimum of a 7-decibel change as the threshold from baseline there with the loci prespecified.

關於微視野測量，我們正在使用黃斑完整性評估系統或 MAIA，這是一種測量視網膜光敏感度的標準化方法。我們正在研究中心靈敏度。正如她所說，FDA 建議我們應該將至少 7 分貝的變化作為從基線開始的閾值，並預先指定位點。

With respect to the maze, as Sue also said and I support, we will be testing one eye separately and then both eyes together. There are 2 courses proposed, the low-luminance and the high-contrast one. And the subject will test at all available light levels. There's a range of levels, again on the various eye combinations: Right eye, left eye, both eyes. On all available courses, they'll start at screening. And then based on where their baseline is, they will be tested throughout the study at the subsequent visits that are in the Skyline study and then in Vista. And they would need a pass to need to stop testing at the various eye combinations.

關於迷宮，正如 Sue 所說，我支持，我們將分別測試一隻眼睛，然後同時測試兩隻眼睛。提出了 2 個課程，低亮度課程和高對比度課程。受試者將在所有可用的光照水平下進行測試。有一系列級別，同樣是在各種眼睛組合上：右眼、左眼、雙眼。在所有可用課程中，他們將從篩選開始。然後根據他們的基線位置，他們將在整個研究期間在 Skyline 研究和 Vista 中的後續訪問中進行測試。他們需要通過才能停止對各種眼睛組合的測試。

And one thing that I'll add here, and Susan mentioned it during the first part of the call, but I think it's very important, is that what we saw in the Phase I/II was improvements in visual sensitivity supported by visual acuity, further supported by structural stabilization and improvement. So we had functional vision, vision function changing, structure changing; and then we saw that the PROs supported that their functional vision, their quality of life was improving. And that is what we would say was the basis for the success of the trial.

我要在這裡添加一件事，Susan 在電話會議的第一部分提到過，但我認為這非常重要，我們在 I/II 階段看到的是視覺敏銳度支持的視覺靈敏度的提高，進一步得到結構穩定和改善的支持。所以我們有了功能視覺，視覺功能變化，結構變化；然後我們看到 PRO 支持他們的功能願景，他們的生活質量正在改善。這就是我們所說的試驗成功的基礎。

And moving forward, what we want to see out of Skyline is the same kind of results: Improvements in visual sensitivity, in -- supportive improvements in visual acuity. We won't quite have structure data at 3 months, but we'll report what their -- what we do see. And then the maze then because -- becomes a much more powerful tool to look at those quality of life, ability to navigate and show support of functional vision.

展望未來，我們希望從 Skyline 中看到的是同樣的結果：視覺靈敏度的提高，以及視力敏銳度的支持性提高。我們不會在 3 個月內獲得結構數據，但我們會報告他們的——我們確實看到了什麼。然後是迷宮，因為 - 成為一個更強大的工具來查看那些生活質量、導航能力和顯示功能視覺的支持。

Our next questions come from the line of Kristen Kluska with Cantor Fitzgerald.

我們的下一個問題來自 Kristen Kluska 和 Cantor Fitzgerald 的台詞。

The first is that I don't believe there are any specific natural history studies that include specific maze assessments I could point to some the pass/fail rates. But I wanted to ask what you believe expectations would be without any treatment. So including areas also where the most errors are most likely to place as well as time to completion.

首先，我不相信有任何特定的自然歷史研究包括特定的迷宮評估，我可以指出一些通過/失敗率。但我想問一下您認為沒有任何治療的期望是什麼。因此，還包括最有可能出現錯誤最多的區域以及完成時間。

Yes. Thank you, Kristen. As far as natural history studies that show the maze over time, there have been some studies with different kinds of mazes. So the Luxturna approval, you can walk through the ADCOM for that indication, and they provided data over a greater than 1-year time frame in a maze in RPE65, which is a different indication, but it is a retinitis pigmentosa indication. And they didn't see any change over time in maze performance. So there was no spontaneous improvement.

是的。謝謝你，克里斯汀。就隨著時間的推移顯示迷宮的自然歷史研究而言，已經有一些針對不同類型迷宮的研究。因此，Luxturna 的批准，您可以通過 ADCOM 了解該適應症，他們在 RPE65 的迷宮中提供了超過 1 年時間框架的數據，這是一個不同的適應症，但它是視網膜色素變性適應症。而且他們沒有發現迷宮性能隨時間發生任何變化。所以沒有自發的改善。

They again, did change up their maze at each visit, so there wasn't the capability for learning. And we think that that's important. And then also the contractor we're working with, the vendor, Ora, they have developed this visual navigation challenge and shown, for retinitis pigmentosa and have shown consistently that it doesn't spontaneously improve. But you're right, there hasn't been a formal, fulsome natural history study conducted.

他們又一次，在每次訪問時確實改變了他們的迷宮，所以沒有學習的能力。我們認為這很重要。然後還有我們正在合作的承包商，供應商，Ora，他們已經開發了這個視覺導航挑戰並展示了視網膜色素變性並且一直表明它不會自發改善。但你是對的，還沒有進行過正式的、豐富的自然歷史研究。

And then, Susan, do you want to comment on the second half of Kristen's question.

然後，蘇珊，你想對克里斯汀問題的後半部分發表評論嗎？

Sure. Could you repeat that second half, please?

當然。請你重複下半句好嗎？

Yes. So I was interested in knowing a little bit more specifically about the maze. Again, this is -- the question pertains to assuming no treatment. Like are there specific [loopholes] in the maze perhaps where you might expect more errors to take place?

是的。所以我有興趣更具體地了解迷宮。同樣，這個問題與假設沒有治療有關。就像迷宮中是否存在特定的[漏洞]，也許您可能會在其中發生更多錯誤？

I guess the best answer for that is we will see with the data that we have. This is a new endpoint for us and part of this will be related to the visual function of each patient. So this will be per-patient measurements. And it will -- it may depend on how advanced their visual field is at the time that they're screened, and therefore, baseline for the study.

我想最好的答案是我們將看到我們擁有的數據。這對我們來說是一個新的終點，其中一部分將與每位患者的視覺功能有關。所以這將是每位患者的測量值。這將 - 這可能取決於他們在篩選時的視野有多先進，因此取決於研究的基線。

I would add, Kristen. There's no specific part of the maze that's supposed to be more difficult than another part of the maze. The maze is supposed to be just very challenging, and the amount of time it takes the patient to try and figure out their way through. And if they make any errors, like stepping off of the course or bumping into the obstacles, that shows that their vision is poor. But there's no specific obstacle that's meant to be significantly more challenging than any other obstacle, if that's what you were asking.

我要補充一點，克里斯汀。迷宮中沒有特定的部分比迷宮的另一部分更難。迷宮應該是非常具有挑戰性的，並且患者需要花費大量時間來嘗試找出他們的出路。如果他們犯了任何錯誤，比如偏離路線或撞到障礙物，那就表明他們的視力很差。但是，沒有任何特定障礙比任何其他障礙都更具挑戰性，如果這就是您要問的。

Yes. That's perfect. And just a follow-up on that. Wanted to ask, I know there's a couple of different mazes, but could you talk about the work that goes into supporting the idea that these separate configurations are all equivalent, given that patients will be running the maze more than once? And then also are there changes to, again, make sure that patients are also not memorizing the course either?

是的。那很完美。只是對此的後續行動。想問一下，我知道有幾個不同的迷宮，但是你能談談支持這些單獨的配置都是等價的想法的工作嗎？考慮到患者將不止一次地運行迷宮？然後是否也有變化，再次確保患者也不會記住課程？

So I'll start with that. I mean, we have worked with Ora on this maze because of their expertise in this type of measurement. And they've worked with many other groups and with experts in the space. And there's a complete science to how they set it up and a manual as to how to change it up. And they've worked very hard to make sure that the different configurations were equivalent and that there were enough different configurations that the patient could not memorize it because I do think that that's important.

所以我將從那個開始。我的意思是，我們在這個迷宮上與 Ora 合作，因為他們在這種測量方面具有專業知識。他們與許多其他團體和該領域的專家合作。他們如何設置它有完整的科學知識，也有關於如何更改它的手冊。他們非常努力地確保不同的配置是等效的，並且有足夠多的不同配置以至於患者無法記住它，因為我確實認為這很重要。

And so how they've set up this maze, they're really working hard to minimize any ability of the patient over time to measure it -- to memorize it. And you have to remember that in some cases, there's 3 to 6 months between visits. So to memorize different configurations of a maze you did under different light conditions and be able to remember it 3 to 6 months later, because it changed in between, I think, is going to be a de minimis issue.

因此，他們如何設置這個迷宮，他們真的很努力地工作，以盡量減少患者隨著時間的推移測量它的任何能力 - 記住它。你必須記住，在某些情況下，兩次訪問之間有 3 到 6 個月的間隔。因此，要記住你在不同光照條件下所做的迷宮的不同配置，並且能夠在 3 到 6 個月後記住它，因為它在兩者之間發生了變化，我認為這將是一個微不足道的問題。

(Operator Instructions) Our next questions come from the line of Yun Zhong with BTIG.

（操作員說明）我們的下一個問題來自 BTIG 的 Yun Zhong 線。

So my questions are on the Phase II/III Vista study. And first, I wanted to confirm the status of the study. Has the study started patient enrollment? And if not, is there anything that you're waiting for before you start patient enrollment, for example, the 3-month data from Skyline study?

所以我的問題是關於 II/III 期 Vista 研究。首先，我想確認研究的狀態。該研究是否已開始患者招募？如果沒有，在開始患者登記之前，您是否正在等待任何東西，例如來自 Skyline 研究的 3 個月數據？

And also from the diagram of the study design, it looks like the interim data analysis is somewhere between month 3 and month 6. And so is that a specific -- sorry, in terms of time point, is that something different from a 3-month interim data analysis?

而且從研究設計的圖表來看，中期數據分析似乎是在第 3 個月和第 6 個月之間的某個時間。因此，具體的 - 抱歉，就時間點而言，與 3-月中數據分析？

Yun, thank you for joining us today. And I'll address these questions. So we have not provided detailed guidance on Vista, except when we will be releasing data. And so that's in the first half of 2023. We've also historically guided and stand by the guidance that we don't need anything specifically out of Skyline to be able to proceed with Vista. We've also guided that Vista has significantly more sites activated and being activated than Skyline did. And now that Skyline has completed enrollment, the Skyline sites are being activated to move into Vista. So those are the pieces of specific guidance that we've provided.

雲，感謝你今天加入我們。我會回答這些問題。所以我們沒有提供關於 Vista 的詳細指導，除非我們將發布數據。所以這是在 2023 年上半年。我們也一直在指導並堅持這樣的指導，即我們不需要 Skyline 中的任何特別內容就可以繼續使用 Vista。我們還指出，與 Skyline 相比，Vista 激活和正在激活的站點要多得多。現在 Skyline 已經完成了註冊，Skyline 站點正在被激活以遷移到 Vista。這些就是我們提供的具體指導。

Okay. So no matter what the outcome will look like from the lower-dose cohort from Skyline, the design of the Vista study is not going to be changed and so will proceed with a high dose plus a low dose?

好的。因此，無論 Skyline 的低劑量隊列的結果如何，Vista 研究的設計都不會改變，因此會繼續進行高劑量加低劑量嗎？

Yes, that's a very important point to bring up, is that the reason we have two active arms in the Vista trial as well as an untreated control is that, from a regulatory perspective, the FDA was very much supportive of having 2 active arms to try and eliminate as much bias as possible in how the patients were thinking about the trial and whether they were highly motivated and focusing really hard to try and get better results if they knew they were treated.

是的，這是一個非常重要的要點，我們在 Vista 試驗中有兩個活躍的手臂以及一個未經處理的控制的原因是，從監管的角度來看，FDA 非常支持有兩個活躍的手臂來嘗試盡可能多地消除患者對試驗的看法以及他們是否有高度的積極性和注意力，如果他們知道自己接受了治療，是否真的努力嘗試並獲得更好的結果。

So the patients don't know which active arm they're in, and that's just as important for the Skyline trial where they're also masked to low and high as it is for Vista. And for a registration-basing trial, the FDA would still want to have there to be 2 arms to eliminate that bias as much as possible. So that is one aspect of the trial that would not change as we move forward.

因此，患者不知道他們在哪隻活躍的手臂上，這對於 Skyline 試驗同樣重要，因為在 Skyline 試驗中，他們也被掩蓋了低和高，就像在 Vista 中一樣。對於基於註冊的試驗，FDA 仍然希望有 2 個分支來盡可能消除這種偏見。所以這是審判的一個方面，不會隨著我們的前進而改變。

Okay. And last question. So I believe you talked about this possibility of modifying the study design of Vista based on the interim data analysis. So I just wanted to confirm if that's still the case. And if so, what could potentially be changed based on the interim data analysis?

好的。最後一個問題。所以我相信你談到了這種根據中期數據分析修改 Vista 研究設計的可能性。所以我只想確認情況是否仍然如此。如果是這樣，根據中期數據分析可能會改變什麼？

Yes. So I think we talked about this during the first portion of the call and later on, is that what we want to be able to do is, as data comes forward, and we're a very data-driven company, we always have the opportunity to have interaction with the FDA and make sure that we're all still comfortable we're moving forward. We would never want to get to the 12-month endpoint, which is the addressable endpoint, and wish we'd had interactions with the FDA.

是的。所以我想我們在電話的第一部分和後來都談到了這個問題，我們希望能夠做的是，隨著數據的出現，我們是一家非常以數據為導向的公司，我們始終擁有有機會與 FDA 進行互動，並確保我們都對我們的前進感到滿意。我們永遠不想達到 12 個月的終點，這是可尋址的終點，並希望我們與 FDA 進行過互動。

And as I said earlier, at the interim analysis of Vista, we'll also have 12-month data from Skyline and 24-month data from the Phase I/II. So it's a robust set of data. And so if there's anything that we feel we would need to adjust or anything we could accelerate, such as dosing the contralateral eye earlier, such as slightly adjusting the number of patients, maybe our statistical power is stronger than we thought going in, we would have that interaction.

正如我之前所說，在 Vista 的中期分析中，我們還將獲得來自 Skyline 的 12 個月數據和來自 Phase I/II 的 24 個月數據。所以這是一組可靠的數據。因此，如果有任何我們認為需要調整或可以加速的事情，例如更早地對對側眼進行給藥，例如稍微調整患者人數，也許我們的統計能力比我們想像的要強，我們會有那種互動。

But it's all going to be based on the data. And there's nothing specific that we would be looking to change. It would be based on the data. And then as I said, at any time based on that data, we would have interactions with the FDA.

但這一切都將基於數據。並且沒有任何具體的內容是我們希望改變的。它將基於數據。然後正如我所說，在任何時候根據這些數據，我們都會與 FDA 進行互動。

Our next questions come from the line of Zegbeh Jallah with ROTH Capital.

我們的下一個問題來自 ROTH Capital 的 Zegbeh Jallah。

I think the first one is just a follow-up to the previous question, and that's just regarding the potential to actually change the patient number for the Vista study. I just wanted to know, is it possible to get any insights as to whether or not you will need that from any of the previous readouts? Specifically, maybe the Skyline 3-month or 12-month data? Could that be informative as well as to whether or not you may have the right power currently?

我認為第一個問題只是對上一個問題的跟進，這只是關於實際改變 Vista 研究患者人數的可能性。我只是想知道，是否可以從之前的任何讀數中了解您是否需要它？具體來說，也許是 Skyline 3 個月或 12 個月的數據？這是否可以提供信息以及您目前是否擁有正確的權力？

Thank you, Zegbeh. I think that it's premature to make any definitive statements about that until we have the data. Data can always be -- data is always very informative. But until we have that data, I would not want to predict what it may or may not allow us to do going forward.

謝謝你，澤格貝。我認為在我們獲得數據之前就此做出任何明確的聲明還為時過早。數據總是可以——數據總是非常有用。但在我們擁有這些數據之前，我不想預測它可能允許或不允許我們做些什麼。

And then just a follow-up here on another question. Just kind of curious as to why a [phase extension] study is not being considered for the achromatopsia program to kind of help bolster the data, especially for the younger pediatric patient population. Or do you think to perhaps like familiarize the sites of the new baseline [were material to] expedite the Phase III study as you did with the XLRP program?

然後只是對另一個問題的跟進。只是有點好奇為什麼不考慮對全色盲計劃進行 [階段擴展] 研究以幫助加強數據，特別是對於年輕的兒科患者群體。或者您是否認為可能喜歡熟悉新基線的站點[是重要的]加快 III 期研究，就像您對 XLRP 計劃所做的那樣？

And then how do you -- how are you thinking about the robustness of the package for the achromatopsia program versus the XLRP program ahead of your meeting with the FDA?

然後你如何 - 在與 FDA 會面之前，你如何考慮色盲程序包與 XLRP 程序包的穩健性？

So Zegbeh, I don't think I understood -- I apologize. I don't think I understood the first part of your question. I think there was interference on the line. But I think you were addressing what we are doing with sites and investigators as we prepare for the end of Phase II. And so if that was the question, we are absolutely involved with all of our investigators as we plan for the end of Phase II meeting. They know that we plan to move the achromatopsia B3 program forward and are interacting with their patient base in that way.

所以 Zegbeh，我想我沒理解——我很抱歉。我不認為我理解你問題的第一部分。我認為線路上有乾擾。但我認為，在我們為第二階段的結束做準備時，你正在談論我們正在與站點和調查人員一起做的事情。因此，如果這是個問題，那麼在我們計劃結束第二階段會議時，我們絕對會與我們所有的調查人員一起參與。他們知道我們計劃推進全色盲 B3 計劃，並以這種方式與他們的患者群進行互動。

Our patient advocacy and patient enrollment teams are reaching out and working through our patient advocacy group connections to make sure patients are aware that we're planning to move the B3 program forward. And so I think we're moving forward with that in mind. We can't plan anything specific, however, until the end of Phase II meeting with the FDA.

我們的患者宣傳和患者登記團隊正在通過我們的患者宣傳小組聯繫開展工作，以確保患者了解我們計劃推進 B3 計劃。所以我認為我們正在考慮這一點。然而，在與 FDA 的第二階段會議結束之前，我們無法計劃任何具體的事情。

And a bit of clarification since my line was breaking up. I was just also wondering why an extension study is not being considered for the achromatopsia program like you did for the XLRP program. Since as you noted, getting sites on board with the new enrollment criteria could help expedite the Phase III study, for example.

還有一點澄清，因為我的線路中斷了。我還想知道為什麼沒有像您對 XLRP 計劃那樣考慮對色盲計劃進行擴展研究。因為正如你所指出的，讓網站加入新的註冊標準可以幫助加快 III 期研究，例如。

So there's a lot of things that come into that historically. I think that we were less confident in exactly dosing when we decided to expand the Skyline study. And also, we were adding the maze as a new endpoint. So we wanted to get some data on the maze as quickly as possible as we were going into the Phase II/III Vista trial.

所以歷史上有很多東西。我認為當我們決定擴大 Skyline 研究時，我們對精確劑量的信心降低了。而且，我們將迷宮添加為新的端點。因此，我們希望在進入 II/III 期 Vista 試驗時盡快獲得有關迷宮的一些數據。

In the case of achromatopsia, it seems very, very clear to us what the appropriate dose is, especially since it's the same dose that looks the best in achromatopsia as XLRP, which is not surprising, because it is the same capsid, same delivery method, same target cell type. So I think we have fewer questions that we want to gather more additional data on, and so feel it's the best use of resources to have that in a Phase II meeting and go directly into a Phase II/III.

在全色盲的情況下，我們似乎非常非常清楚合適的劑量是多少，尤其是因為它與 XLRP 在全色盲中看起來效果最好的劑量相同，這並不奇怪，因為它是相同的衣殼，相同的遞送方法, 相同的目標細胞類型。所以我認為我們想要收集更多額外數據的問題更少了，所以我覺得在第二階段會議上討論這些問題並直接進入第二階段/第三階段是對資源的最佳利用。

Got it. And then the last one here is just about the commercial or pre-commercialize vision preparations. Can you comment on some additional efforts beyond obviously executing on the clinical study and preparing the manufacturing facility?

知道了。然後這裡的最後一個是關於商業或商業化前的願景準備。除了明顯執行臨床研究和準備製造設施之外，您能否評論一些額外的努力？

And then I think just out of curiosity as well, is it possible that there could be some downtime at the manufacturing facility where you could manufacture products for other companies? I was just wondering how well utilized the space is going to be.

然後我也出於好奇想，您可以為其他公司生產產品的製造工廠是否可能會出現一些停機時間？我只是想知道空間的利用情況如何。

So on commercialization preparation, we're doing a lot of work with some third-party vendors to make sure that we understand the patient population distribution, we understand the feelings of -- and input -- getting input from payers and physicians and patients. So we're doing a lot of work to prepare for development of a commercialization plan.

因此，在商業化準備方面，我們正在與一些第三方供應商進行大量工作，以確保我們了解患者人口分佈，我們了解從付款人、醫生和患者那裡獲得輸入的感受和輸入。因此，我們正在做大量工作來準備製定商業化計劃。

As far as the manufacturing facility, you're absolutely correct. We will not fully utilize the capacity of that facility with our own production. However, we do not want to, in any way, become a CDMO. That would not be a good utilization of our resources. But if we found some like-minded companies that wanted to use some of the capacity, we have been looking into that as a possibility. But just want to be clear, we have no change in strategy and/or any desire to become a CDMO.

就製造設施而言，你是絕對正確的。我們不會在自己的生產中充分利用該設施的產能。但是，我們不想以任何方式成為 CDMO。這不會很好地利用我們的資源。但如果我們發現一些志同道合的公司想要使用部分產能，我們一直在研究這種可能性。但只是想明確一點，我們沒有改變戰略和/或成為 CDMO 的任何願望。

Got it. And congrats again on the progress.

知道了。並再次祝賀進展。

Thank you. There are no further questions at this time. I would like to turn the call back over to Sue Washer for any closing comments.

謝謝。目前沒有其他問題。我想將電話轉回給 Sue Washer 以徵求任何結束意見。

Thank you. Completing enrollment in the Skyline trial and reporting additional pediatric data for the achromatopsia program were important milestones that support continued advancement of our 2 lead clinical candidates. We believe that the data generated to date for both AGTC-501 and AGTC-401 derisks their continued development and support differentiated product profiles that have been best-in-class potential.

謝謝。完成 Skyline 試驗的註冊並報告全色盲項目的額外兒科數據是支持我們 2 位主要臨床候選人持續進步的重要里程碑。我們認為，迄今為止為 AGTC-501 和 AGTC-401 生成的數據降低了它們繼續開發的風險，並支持具有同類最佳潛力的差異化產品概況。

Additionally, while we do not provide an update on our preclinical pipeline programs today, we continue to make progress across the portfolio and are excited about the multiple opportunities these programs provide to address unmet patient need in a broader array of indications, including additional ophthalmic indications and central nervous system indications.

此外，雖然我們今天沒有提供臨床前管道計劃的更新，但我們繼續在整個產品組合中取得進展，並對這些計劃提供的多種機會感到興奮，這些機會可以解決更廣泛適應症（包括其他眼科適應症）中未滿足的患者需求和中樞神經系統適應症。

Our collaboration with Otonomy on a program targeting nonsyndromic hearing loss also continues to advance. And we expect Otonomy to begin toxicology and biodistribution studies this year to support filing of a new drug application, IND, in the first half of 2023.

我們與 Otonomy 在一項針對非綜合徵性聽力損失的項目上的合作也在繼續推進。我們預計 Otonomy 今年將開始毒理學和生物分佈研究，以支持在 2023 年上半年提交新藥申請 IND。

Our expanded management team has the expertise and dedication to build on our momentum and enhance our ability to realize the clinical and commercial value of our diversified pipeline. We remain grateful to the patients, physicians and advocacy communities for their enthusiasm and support of our clinical trials.

我們擴大後的管理團隊擁有專業知識和奉獻精神，可以鞏固我們的勢頭並增強我們實現多元化管道的臨床和商業價值的能力。我們仍然感謝患者、醫生和倡導團體對我們臨床試驗的熱情和支持。

We expect to achieve additional milestones in our XLRP and achromatopsia B3 program over the next 12 months that will firmly solidify our leadership in the inherited retinal disease gene therapy space. And I look forward to sharing our progress with you as we work to bring these therapies to patients whose lives will truly be brightened by our success.

我們希望在未來 12 個月內在我們的 XLRP 和全色盲 B3 計劃中實現更多的里程碑，這將鞏固我們在遺傳性視網膜疾病基因治療領域的領導地位。我期待著與您分享我們的進展，因為我們致力於將這些療法帶給患者，他們的生活將因我們的成功而真正變得光明。

Thank you for joining us on today's call.

感謝您參加今天的電話會議。

This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.

今天的電話會議到此結束。感謝您的參與。此時您可以斷開線路。享受你剩下的一天。