Sangamo Therapeutics Inc (SGMO) 2025 Q1 法說會逐字稿

Good afternoon, and welcome to the Sangamo Therapeutics' first quarter 2025 teleconference call. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker today, Louise Wilkie, Vice President of Investor Relations and Corporate Communications. Please go ahead.

下午好，歡迎參加 Sangamo Therapeutics 2025 年第一季電話會議。請注意，今天的會議正在錄音。現在，我想將會議交給今天的演講者、投資者關係和企業傳播副總裁 Louise Wilkie。請繼續。

Thank you. Good afternoon, everyone. Thank you for joining us on the call today. On this call are several members of the Sangamo executive leadership team, including Sandy Macrae, Chief Executive Officer; Prathyusha Duraibabu, Chief Financial Officer; and Nathalie Dubois-Stringfellow, Chief Development Officer. Slides from our corporate presentation can be found on our website, sangamo.com, and under the Presentations page of the Investors and Media section.

謝謝。大家下午好。感謝您今天參加我們的電話會議。參加此次電話會議的有 Sangamo 執行領導團隊的幾位成員，包括執行長 Sandy Macrae、財務長 Prathyusha Duraibabu 和首席開發長 Nathalie Dubois-Stringfellow。我們的公司介紹的幻燈片可以在我們的網站 sangamo.com 以及投資者和媒體部分的簡報頁面上找到。

This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to: statements relating to Sangamo's cash runway and operating expense guidance; the anticipated closing of the announced underwritten offering; Sangamo's plans to obtain additional capital and its ability to continue to operate as a going concern; the therapeutic and commercial potential and value of Sangamo's product candidates and technologies; Sangamo's ability to earn and receive payments from its collaboration and license agreements; Sangamo's ability to establish and maintain collaborations and strategic partnerships, including for its Fabry disease program, the anticipated plans, and time lines of Sangamo and its collaborators for clinical trials, clinical data presentations, and releases; regulatory submissions and regulatory approvals; upcoming catalysts and milestones; and other statements that are not historical fact.

本次電話會議包括有關 Sangamo 目前預期的前瞻性陳述。這些聲明包括但不限於：與 Sangamo 的現金流量和營運費用指引有關的聲明；宣布的承銷發行的預期結束；Sangamo 獲得額外資本的計劃及其繼續作為持續經營企業運營的能力；Sangamo 候選產品和技術的治療和商業潛力和價值；Sangamo 從其合作和許可協議中獲得的合作和許可協議以及合作夥伴關係的能力；及其合作者的臨床試驗、臨床數據展示和發布的時間表；監管提交和監管批准；即將到來的催化劑和里程碑；以及其他非歷史事實的陳述。

Actual results may differ materially from what we discuss today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically in our annual report on Form 10-K for the fiscal year ended December 31, 2024, and our quarterly report on Form 10-Q for the fiscal quarter ended March 31, 2025, and subsequent filings and reports that Sangamo makes from time to time with the SEC. The forward-looking statements stated today are made as of today, and we undertake no duty to update such information, except as required by law.

實際結果可能與我們今天討論的結果有重大差異。這些聲明受到我們向美國證券交易委員會 (SEC) 提交的文件中討論的某些風險和不確定性的影響，特別是在我們截至 2024 年 12 月 31 日的財政年度的 10-K 表年度報告和截至 2025 年 3 月 31 日的財政季度的 10-Q 表年度報告和截至 2025 年 3 月 31 日的財政季度的 10-Q 表季度報告以及美國證券委員會的後續文件和年度證券。今天所述的前瞻性陳述是截至今天做出的，除非法律要求，否則我們不承擔更新此類資訊的義務。

Please note that all forward-looking statements about our future plans and expectations are subject to our ability to secure adequate additional funding. Now I'll turn the call over to our CEO, Sandy Macrae.

請注意，有關我們未來計劃和期望的所有前瞻性陳述都取決於我們獲得足夠額外資金的能力。現在我將電話轉給我們的執行長桑迪·麥克雷 (Sandy Macrae)。

Thank you, Louise, and good afternoon to everyone joining the call. It's only been a couple of months since our fourth quarter call, but I'm pleased to share with you some company progress across a variety of areas, including our capsid engineering platform, our neurology pipeline, our Fabry program, and our finances.

謝謝你，路易絲，祝大家午安。距離我們第四季度電話會議僅僅過去了幾個月，但我很高興與大家分享公司在各個領域的進展，包括我們的衣殼工程平台、我們的神經病學管道、我們的法布里計劃和我們的財務狀況。

Beginning with our capsid engineering platform. In April, we announced our third capsid license agreement since we shared the discovery of our industry-leading neurotropic delivery capsid STAC-BBB. We are pleased to sign an agreement with Eli Lilly and Company, granting Lilly a worldwide exclusive license to STAC-BBB for up to five potential disease targets of the central nervous system.

從我們的衣殼工程平台開始。今年 4 月，我們宣布了自我們分享業界領先的神經營養遞送衣殼 STAC-BBB 的發現以來的第三份衣殼許可協議。我們很高興與禮來公司簽署協議，授予禮來公司 STAC-BBB 的全球獨家許可，用於治療多達五種中樞神經系統潛在疾病目標。

We have received the $18 million upfront license fee for the first target and are eligible to earn up to $1.4 billion in additional license target fees and milestone payments across all five potential disease targets as well as tiered royalties on potential net sales.

我們已經收到了針對第一個目標的 1800 萬美元預付許可費，並且有資格獲得針對所有五個潛在疾病目標的最高 14 億美元的額外許可目標費和里程碑付款以及潛在淨銷售額的分級特許權使用費。

We are thrilled to have signed this third important agreement, further demonstrating that we are a collaborator of choice for neurotrophic capsids. With Genentech, Astellas, and now Lilly, we have great partners in neuroscience for our technology, and we continue to engage in discussions with new potential collaborators for STAC-BBB.

我們很高興簽署了第三份重要協議，這進一步證明我們是神經營養衣殼的首選合作者。有了 Genentech、Astellas 以及現在的 Lilly，我們在神經科學領域擁有了優秀的技術合作夥伴，並且我們將繼續與 STAC-BBB 的新潛在合作者進行討論。

Turning to our neurology pipeline programs. This quarter, we continue to advance clinical study preparations for ST-503, our investigational epigenetic regulator for the treatment of chronic neuropathic pain. We are preparing for a Phase I/II study to assess the safety, tolerability, and preliminary efficacy of a onetime dose of ST-503, our investigational epigenetic regulator that will be administered intrathecally to patients with intractable pain due to idiopathic small fiber neuropathy or ISFN.

轉向我們的神經病學管道計畫。本季度，我們繼續推進 ST-503 的臨床研究準備，ST-503 是我們用於治療慢性神經性疼痛的試驗性表觀遺傳調節劑。我們正在準備進行 I/II 期研究，以評估一次性使用 ST-503 的安全性、耐受性和初步療效。 ST-503 是我們正在研究的表觀遺傳調節劑，將透過鞘內給藥的方式用於治療因特發性小纖維神經病變或 ISFN 引起的頑固性疼痛的患者。

We plan to begin patient enrollment and dosing for the ST-503 study in mid-2025 and anticipate having preliminary proof of efficacy data in the fourth quarter of 2026. We also continue to advance clinical trial authorization or CTA enabling activities for ST-506, our epigenetic regulator for the treatment of Prion disease to be delivered intravenously using our own STAC-BBB.

我們計劃於 2025 年中期開始 ST-503 研究的患者招募和給藥，並預計在 2026 年第四季獲得初步療效證明數據。我們也繼續推進 ST-506 的臨床試驗授權或 CTA 支持活動，ST-506 是我們用於治療朊病毒疾病的表觀遺傳調節劑，將使用我們自己的 STAC-BBB 進行靜脈注射。

We are extremely proud to have been selected to present during the prestigious Presidential Symposium at this week's ASGCT Annual Meeting in New Orleans. We look forward to showcasing our potent combination of epigenetic regulation and capsid delivery technology in Prion disease and describing the profound survival benefits we observed when administered to post-symptomatic mice.

我們非常榮幸能被選中在本週於新奧爾良舉行的 ASGCT 年會上發表著名的總統研討會演講。我們期待展示我們在朊病毒疾病中表觀遺傳調控和衣殼傳遞技術的強大組合，並描述我們在對症狀後小鼠施用時觀察到的顯著生存益處。

We will also describe the sustained brain-wide suppression of prion protein expression in both mouse and nonhuman primate models, supporting its potential as a one time therapeutic approach for Prion disease. We plan to begin clinical trial enrollment and dosing for ST-506 in mid-2026 and expect to have preliminary clinical data in the fourth quarter of 2026.

我們還將描述小鼠和非人類靈長類動物模型中朊病毒蛋白表達的持續全腦抑制，支持其作為朊病毒疾病一次性治療方法的潛力。我們計劃於 2026 年中期開始 ST-506 的臨床試驗招募和劑量測定，並預計將於 2026 年第四季獲得初步臨床數據。

In addition to the PM presentation, we have had eight abstracts accepted by ASGCT. I am very proud of our scientists and look forward to us showcasing the progression of our neurology pipeline, including advances in zinc finger epigenetic regulation, the latest innovations in capsid delivery engineering, and developments in our modular integrase technology.

除了首相演講之外，我們還有八篇摘要被ASGCT錄用。我為我們的科學家感到無比自豪，並期待著展示我們神經病學研發管線的進展，包括鋅指表觀遺傳調控方面的進展、衣殼遞送工程的最新創新以及模組化整合酶技術的進展。

Moving to our late-stage Fabry program. Last week, we were excited to announce a number of important derisking milestones in the pathway to the anticipated BLA submission for ST-920. All dose patients in the Phase I/II STAAR study have now completed at least 52 weeks of follow-up, a key milestone required by the FDA for an accelerated approval regulatory pathway for ST-920.

轉至我們後期的法布里-巴爾金細胞瘤計畫。上週，我們很高興地宣布，在 ST-920 預期提交生物製品許可申請 (BLA) 的道路上，我們取得了一系列重要的風險降低里程碑。I/II 期 STAAR 研究中的所有劑量患者現已完成至少 52 週的隨訪，這是 FDA 為 ST-920 加速審批監管途徑所要求的關鍵里程碑。

Importantly, preliminary analysis of the clinical data collected as of this 52-week milestone date across all 32 dose patients indicated that the mean eGFR slope continued to remain positive. The product candidate continues to be well tolerated and a pivotal data readout is now expected by the end of this quarter. Furthermore, in April of this year, Sangamo held a productive Type B meeting with the FDA, providing us with a clear chemistry, manufacturing and controls or CMC pathway to the planned BLA submission.

重要的是，對所有 32 名劑量患者截至此 52 週里程碑日期收集的臨床數據的初步分析表明，平均 eGFR 斜率繼續保持正值。該產品候選藥物繼續具有良好的耐受性，預計本季末將獲得關鍵數據讀數。此外，今年 4 月，Sangamo 與 FDA 舉行了一次富有成效的 B 類會議，為我們提供了清晰的化學、製造和控製或 CMC 途徑，以提交計劃的 BLA。

We were encouraged by the productive nature of the discussions and the engagement from those FDA representatives in attendance and are happy to have clarity on these important activities from the agency.

我們對與會 FDA 代表的富有成效的討論和參與感到鼓舞，並很高興能夠明確該機構的這些重要活動。

With the newly agreed CMC pathway, we believe we have a clear line of sight to an anticipated BLA submission as early as the first quarter of 2026, which would facilitate a potential approval and commercial launch of ST-920 as early as the second half of that year.

透過新商定的 CMC 途徑，我們相信我們預計最早在 2026 年第一季提交 BLA，這將有助於最早在當年下半年批准和商業推出 ST-920。

As you can imagine, this clinical and regulatory progress has been well received by our potential commercial partners, and we are hopeful that these derisking events may accelerate our ongoing negotiations.

正如您所想像的，這項臨床和監管進展受到了我們潛在商業夥伴的歡迎，我們希望這些降低風險的事件能加速我們正在進行的談判。

We remain committed to securing an anticipated partnership that is best suited to bring ST-920 to Fabry patients upon potential approval, and that provides near-term capital for Sangamo to advance our core neurology pipeline.

我們仍然致力於建立預期的合作夥伴關係，以便在獲得批准後將 ST-920 帶給法布瑞氏症患者，並為 Sangamo 提供短期資本以推進我們的核心神經病學產品線。

As I've said before, in order to execute on our plans and deliver on this promising neurology genomic medicine pipeline, Sangamo must be sufficiently capitalized. We must have the resources to fund us through proof of concept in both our chronic neuropathic pain and prion disease programs while operating a lean, efficient, and focused organization.

正如我之前所說，為了執行我們的計劃並實現這一有前景的神經病學基因組醫學管道，Sangamo 必須擁有足夠的資本。我們必須擁有資源來資助我們透過慢性神經性疼痛和朊病毒疾病計畫的概念驗證，同時運作一個精簡、高效、專注的組織。

In support of this strategy, today, we announced the pricing of an equity offering to extend our immediate cash runway. We're optimistic these funds will provide us with the bridge that we believe is necessary to secure a Fabry commercialization agreement.

為了支持這項策略，今天，我們宣布了股票發行定價，以延長我們的即時現金流。我們樂觀地認為這些資金將為我們提供達成法布瑞商業化協議所需的橋樑。

We believe that this modest infusion of equity capital alongside the recent positive Fabry clinical and regulatory derisking events will allow us to secure the right commercial partner for the company and for our shareholders.

我們相信，這次適度的股權資本注入，加上近期積極的法布瑞氏症臨床和監管風險降低事件，將使我們能夠為公司和股東找到合適的商業夥伴。

We also continue to engage in promising business development discussions across our technology platforms. We have opportunities for potential funding through both new and existing STAC-BBB collaboration partners with our zinc finger platform and through collaborative research agreements related to our modular integrase or MINT platform, all of which demonstrate the ongoing interest in our technology.

我們也將繼續在我們的技術平台上開展有前景的業務發展討論。我們有機會透過新的和現有的 STAC-BBB 合作夥伴利用我們的鋅指平台以及透過與我們的模組化整合酶或 MINT 平台相關的合作研究協議獲得潛在資金，所有這些都表明了人們對我們技術的持續興趣。

We look forward to sharing more information when we can. With that overview of our business progress and strategy, I'd now like to hand it over to Prathyusha Duraibabu, our Chief Financial Officer, who will provide more context on long-term vision and financial strategy to support our neurology-focused mission. Prathyusha?

我們期待在可能的情況下分享更多資訊。在概述了我們的業務進展和戰略之後，我現在想將其交給我們的首席財務官 Prathyusha Duraibabu，他將提供更多有關長期願景和財務戰略的背景信息，以支持我們以神經病學為重點的使命。普拉蒂尤沙？

Thank you, Sandy. I'd like to begin by emphasizing our long-term vision for Sangamo as a neurology-focused genomic medicine company. We strongly believe in the potential of our neurology pipeline to deliver transformational therapies for patients as well as significant value for our shareholders.

謝謝你，桑迪。首先，我想強調一下我們對 Sangamo 作為一家專注於神經病學的基因組醫學公司的長期願景。我們堅信我們的神經病學產品線能夠為患者提供變革性療法，並為我們的股東帶來巨大價值。

Our goal is to appropriately fund the company to achieve clinical proof-of-concept data across both our chronic neuropathic pain and prion disease programs. These milestones represent critical potential value inflection points that could significantly change the trajectory of our company.

我們的目標是為公司提供適當的資金，以在我們的慢性神經性疼痛和朊病毒疾病計畫中獲得臨床概念驗證數據。這些里程碑代表著關鍵的潛在價值轉折點，可能會顯著改變我們公司的發展軌跡。

To achieve these important milestones, we have a financial strategy with both short- and long-term components. In the near term, the equity financing we announced today is necessary to solidify Sangamo's immediate financing needs. We believe the offering proceeds will extend our runway to late in the third quarter of this year.

為了實現這些重要里程碑，我們制定了短期和長期財務策略。短期內，我們今天宣布的股權融資對於鞏固 Sangamo 的即時融資需求是必要的。我們相信，發行所得將使我們的跑道延長至今年第三季末。

More importantly, this bridge financing provides us the time we believe that we need to secure the right Fabry commercial partnership, one that would fund our neurology mission in the near term and create value for shareholders over the longer term. We've already made significant progress in transforming our financial profile.

更重要的是，這種過橋融資為我們提供了我們認為需要的時間，以確保建立正確的法布里商業合作夥伴關係，該合作夥伴關係將在短期內為我們的神經病學使命提供資金，並在長期內為股東創造價值。我們在轉變財務狀況方面已經取得了重大進展。

In 2024, we reduced our non-GAAP operating expenses by 50% year on year by carefully focusing the organization on our most important priorities. We are leaving no stone unturned in seeking additional cost savings and are looking at ways to further reduce our operating expenses to maximize the efficiency of the go-forward neurology company.

2024 年，我們透過精心將組織重點放在最重要的優先事項上，將非 GAAP 營運費用年減了 50%。我們正在竭盡全力尋求額外的成本節約，並正在尋找進一步降低營運費用的方法，以最大限度地提高前進的神經病學公司的效率。

We are committed to operating as leanly as possible while continuing to advance our two neurology programs at a steady pace. We believe this disciplined approach to capital allocation will ensure that we have the specific talent and capabilities to execute on our neurology mission while extending our runway through our key value-creating milestones. I'll now hand it back to Sandy for closing remarks.

我們致力於盡可能精簡運營，同時繼續穩步推進我們的兩個神經病學計畫。我們相信，這種嚴謹的資本配置方法將確保我們擁有特定的人才和能力來執行我們的神經病學使命，同時透過我們的關鍵價值創造里程碑來延長我們的跑道。現在我將發言交還給桑迪，請她做最後發言。

Thank you, Prathyusha. I'm pleased with the progress we have made this year so far. We signed our third STAC-BBB license agreement this time with Lilly, reinforcing that Sangamo is a collaborator of choice for neurotrophic capsids.

謝謝你，Prathyusha。我對我們今年迄今為止的進展感到滿意。此次，我們與禮來公司簽署了第三份 STAC-BBB 授權協議，進一步證明 Sangamo 是神經營養衣殼領域的首選合作夥伴。

We continue to advance our ST-503 program for the treatment of intractal pain due to ISFN ahead of the start of a planned patient enrollment and dosing in mid-2025. We achieved significant clinical and CMC derisking milestones in our pathway to anticipated BLA submission for our Fabry disease program, and we have advanced multiple potential business development discussions across a range of Sangamo technologies, including STAC-BBB, our zinc finger platform, and our MINT platform, while securing additional capital to support our near-term efforts.

我們將繼續推進 ST-503 計劃，用於治療因 ISFN 引起的內科疼痛，並計劃於 2025 年中期開始招募患者並開始給藥。我們在法布瑞氏症計畫預期提交 BLA 的道路上取得了重要的臨床和 CMC 風險降低里程碑，並且我們已經就一系列 Sangamo 技術（包括 STAC-BBB、我們的鋅指平台和我們的 MINT 平台）推進了多項潛在業務發展討論，同時獲得了額外資金來支持我們的近期努力。

We remain resolutely focused on solving our long-term funding needs and partnering our Fabry disease program in an effort to provide sustainable and long-term funding for our promising neurology genomic medicine pipeline.

我們始終堅定地致力於解決我們的長​​期資金需求並與我們的法布瑞氏症計畫合作，努力為我們有前景的神經病學基因組醫學管道提供可持續的長期資金。

In closing, I would encourage you to engage with the data we'll be presenting at this week's ASGCT Annual Meeting, which will be made available on the Sangamo website once data embargoes have lifted. These presentations will further demonstrate the scientific foundation of our pipeline and the potential of our therapeutic approach to address significant unmet medical needs.

最後，我鼓勵您關注我們將在本週的 ASGCT 年會上展示的數據，一旦數據禁運解除，這些數據將在 Sangamo 網站上公佈。這些演示將進一步展示我們產品線的科學基礎以及我們的治療方法解決重大未滿足醫療需求的潛力。

As always, we thank you for your continued support of Sangamo. Operator, please open the line for questions.

像往常一樣，我們感謝您對 Sangamo 的持續支持。接線員，請打開熱線來回答問題。

Maury Raycroft, Jefferies.

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

This is James on for Maury. Congrats on the progress. Just to start off, could you provide more color on what exactly you plan to show in the top line eGFR data? Do you plan to show just the eGFR slope or there be other quality of life endpoints? Also, do you plan to show an NHS analysis to contextualize the improvements you're seeing in eGFR?

這是詹姆斯 (James) 代替莫里 (Maury) 上場。恭喜你取得進展。首先，您能否詳細說明您計劃在頂線 eGFR 數據中顯示什麼？您是否計劃僅顯示 eGFR 斜率或還有其他生活品質終點？此外，您是否計劃展示 NHS 分析來說明您在 eGFR 中看到的改進？

And if so, can you provide some color on the statistical plan and p-value threshold?

如果可以，您能否提供一些有關統計計劃和 p 值閾值的詳細資訊？

Thank you for your questions. Nathalie, can you talk to these?

感謝您的提問。娜塔莉，你能談談這些嗎？

Yes. Yes. So we're really happy to have dosed all the patients and now have passed the 1-year milestone required by the FDA for an accelerated approval regulatory pathway. We will, of course, share in the top line data the updated mean eGFR slope, and we will comment on additional information at a later date.

是的。是的。因此，我們非常高興能夠為所有患者提供藥物，並且已經通過了 FDA 加速審批監管途徑所要求的 1 年里程碑。當然，我們將在頂線數據中分享更新的平均 eGFR 斜率，並且我們將在稍後評論更多資訊。

It's fair to say, Nathalie, that at that time, we'll also have 19 patients who will have achieved two years data. Absolutely. So it really is a robust data set. We understand the excitement people have to see this data in full, and we will show as much as possible as we can of the top line data as we prepare it for the BLA submission.

可以公平地說，娜塔莉，到那時，我們還將有 19 名患者獲得兩年的數據。絕對地。所以它確實是一個強大的數據集。我們理解人們看到完整數據時的興奮之情，我們將在準備提交 BLA 時盡可能多地展示最重要的數據。

Yes. And as to the statistical analysis, we are not commenting at this time, but we have I agree with the FDA on our Type B meeting with them. So we feel like we -- it's a standard way to doing it and have agreed with the FDA on the path forward.

是的。至於統計分析，我們目前不發表評論，但我們同意 FDA 在與他們的 B 型會議上的意見。因此，我們覺得——這是一種標準的做法，我們已經與 FDA 就未來發展方向達成了一致。

Got it. And just one really quick follow-up. Now that you're sort of in the final stages of securing a potential SAR partnership, how many partners are you -- potential partners are you currently in conversations? And what can you really tell us about those ongoing discussions at this point?

知道了。還有一個非常快速的後續問題。現在，您已經進入了建立潛在 SAR 合作夥伴關係的最後階段，您目前正在與多少​​潛在合作夥伴進行洽談？您能告訴我們關於目前正在進行的討論的哪些資訊嗎？

You can imagine that that's not something that we're able to comment. But it's fair to say there are multiple potential partners that we're talking to. And I think for all of them, the Type B meeting was very helpful because it gave a clear path for the CMC, which is something that is very important for any gene therapy BLA and approval.

你可以想像這不是我們能夠評論的事情。但公平地說，我們正在與多個潛在合作夥伴進行洽談。我認為對於所有人來說，B 類會議都非常有幫助，因為它為 CMC 提供了清晰的道路，這對於任何基因療法 BLA 和批准都非常重要。

So we were very pleased with that result. We're very pleased with how straightforward the interaction with the agency was and how helpful they were because I know for people like you, predictability of the process and the approval process is very important.

所以我們對這個結果非常滿意。我們對與該機構的互動如此直接以及他們提供的幫助感到非常滿意，因為我知道對於像您這樣的人來說，流程和審批流程的可預測性非常重要。

Nicole Germino, Truist.

妮可·傑米諾（Nicole Germino），Truist。

So you previously mentioned potential interesting partners for Fabry and Hem A. Has the pace of those conversations gone? Have they changed in any way given the macro landscape with changes at FDA? And do you see any added pressure around cell and gene therapies in particular?

所以你之前提到了 Fabry 和 Hem A 的潛在有趣的合作夥伴。這些對話的節奏有沒有變快？鑑於 FDA 的宏觀形勢變化，它們有任何變化嗎？您是否認為細胞和基因療法有額外的壓力？

So Nicole, sorry, your line was quite hard to hear here. I think I heard you ask us to comment on hemophilia A and the agency's attitude to gene therapy. Is that fair?

所以妮可，很抱歉，你的話在這裡很難聽清楚。我想我聽到您要求我們對血友病 A 和該機構對基因治療的態度發表評論。這樣公平嗎？

Yes. And Fabry disease.

是的。還有法布瑞氏症。

So as I kind of alluded to in the last answer, the remarkable thing about the agency interaction we just went through was how unremarkable it was and how helpful the agency was. We -- they send you answers to your written questions before the meeting. They came in on time, and they were very detailed. They had the -- all the right people at the most senior level in the meeting.

因此，正如我在上一個回答中提到的那樣，我們剛剛經歷的與代理商的互動的非凡之處在於它是多麼的平凡，以及代理商是多麼的有幫助。我們—他們會在會議之前向您發送您書面問題的答案。他們準時到達，並且非常細心。他們讓所有最高級別的合適人員都參加了會議。

And we got the answers, the formal minutes of the meeting within a week of the meeting where they could take up to 30 days. And so in every form of interaction we've had, we have found them unchanged in how they are looking at our Fabry disease program. And when we look at the interactions that Pfizer had across the hem A, they also seem to have been very positive about that. So we are not seeing any change.

我們在會議結束後一周內就得到了答复，也就是會議的正式記錄，而他們可能需要長達 30 天的時間。因此，在我們進行的每一種形式的互動中，我們都發現他們對我們的法布瑞氏症計畫的看法沒有改變。當我們觀察輝瑞公司在整個血液 A 中的互動時，他們似乎也對此持非常積極的態度。所以我們沒有看到任何變化。

I'm sure, like us, you are very aware of the announcements and the concern about funding and about resourcing at the agency, but we've not seen any evidence of that, and it has not impacted anything to do with our program.

我確信，和我們一樣，您也非常清楚這些公告以及對該機構資金和資源的擔憂，但我們沒有看到任何證據表明這一點，而且這也沒有影響到我們計劃的任何事情。

Okay. And then one quick question and follow-up. So given the current administration's concern around drug pricing, how do you think that will impact gene therapy uptake and pricing in US and ex US

好的。然後是一個快速問題和後續問題。因此，鑑於現任政府對藥品定價的擔憂，您認為這將如何影響美國及美國以外地區的基因療法的採用和定價

I think there's a long way to go in those discussions around drug pricing. I think that the pharmaceutical industry is a very important industry in America. And I'm sure as someone who sits on the Board of Bio that Bio will be having very detailed and hopefully productive conversations with the administration to find a good way through this.

我認為有關藥品定價的討論還有很長的路要走。我認為製藥業是美國非常重要的產業。作為 Bio 董事會成員，我確信 Bio 將與管理層進行非常詳細且富有成效的對話，以找到解決這個問題的好方法。

Yanan Zhu, Wells Fargo.

朱亞南，富國銀行。

This is (inaudible) on for Yana. Just to clarify on the prior questions. On the regular path for Fabry, do you still plan to file based on 52-week eGFR data? And is static versus baseline required for eGFR?

這是（聽不清楚）為 Yana 開啟的。只是為了澄清先前的問題。在法布里-布里淵 (Fabry) 的常規治療過程中，您是否仍計劃根據 52 週 eGFR 數據進行歸檔？eGFR 是否需要靜態與基線？

Yes, absolutely. We are absolutely pursuing the agreement we had with the FDA to use 52 weeks eGFR for the entirety of the patient population in the Phase I/II study. We have collected all the data from the 32 patients, and we are seeing it. So we expect to share the top line data at the end of the quarter, and then this will be the basis for the data in our BLA.

是的，絕對是。我們絕對會遵守與 FDA 達成的協議，在 I/II 期研究中對整個患者群體使用 52 週 eGFR。我們已經收集了 32 名患者的所有數據，並且正在查看。因此，我們預計將在本季末分享頂線數據，然後這將成為我們 BLA 中數據的基礎。

And it's very important that we emphasize how much supportive data there is beyond the eGFR. We have got agreement with the agency for submission based on that as the primary endpoint. But I think the thing that convinces the agency and has made this such a compelling medicine for us is that every other indication index of success in the trial is going in the same direction. So pain scores, Fabry scores, SF-36.

我們必須強調，除了 eGFR 之外，還有多少支持數據。我們已與該機構達成協議，以此作為主要終點進行提交。但我認為，讓該機構信服並使其成為我們如此青睞的藥物的原因是，試驗中所有其他成功的指標都朝著同一個方向發展。因此有疼痛評分、法布瑞評分、SF-36。

Yes. And the general safety is very good, very well tolerated. The patient in general, are feeling better and our alpha-Gal level remain high in all patients.

是的。而且整體安全性非常好，耐受性非常好。總體而言，患者感覺好多了，並且所有患者的 alpha-Gal 水平仍然很高。

And some of these patients are now out to four plus years.

其中有些患者已經病危四年多了。

Four plus years, yes.

是的，四年多了。

Sorry, maybe you already commented on it. And is static versus baseline required for eGFR?

抱歉，也許您已經對此發表了評論。eGFR 是否需要靜態與基線？

We'll be looking at a variety of statistical methods to describe the difference in eGFR. But we said last week or the week before in our announcement that the eGFR remains positive. So the slope of the EGR remains positive.

我們將研究多種統計方法來描述 eGFR 的差異。但我們在上週或前週的公告中表示，eGFR 仍然保持正值。因此 EGR 的斜率保持為正。

Luis Santos, H.C. Wainwright.

路易斯桑托斯、H.C. 溫賴特。

Congratulations on the selection of your talk for the presidential symposium and your impressive presence at ASGCT. Regarding Fabry, I don't know if I missed this, but are the patients who were on ERT still all off ERT? Or were there any relapse?

恭喜您的演講被選為總統研討會的演講者，並祝賀您在 ASGCT 上令人印象深刻的表現。關於法布瑞氏症，我不知道我是否錯過了這一點，但是接受 ERT 治療的患者是否仍然不再接受 ERT 治療？或有復發嗎？

Yes. All patients -- the 18 patients that started on ERT out of our 32 patients are still off ERT.

是的。所有患者－我們 32 名患者中，有 18 名開始接受 ERT 治療，但目前仍未接受 ERT 治療。

And for the -- I know that you mentioned you're not commenting so much on the statistical analysis plan, but the eGFR slope, you said it remains positive, but is there any threshold that we should be looking at as a minimum? Or is there any actual statistical significance? I think prior questions were asking about this already, but I'm not sure if I was clear on that.

對於——我知道您提到您對統計分析計劃沒有太多評論，但是您說 eGFR 斜率仍然為正，但是是否存在我們應該作為最低限度考慮的閾值？或有實際的統計意義嗎？我認為之前的問題已經問過這個問題了，但我不確定我是否清楚這一點。

We're not commenting on this right now, but what I can tell you is the mean eGFR slope remains positive.

我們現在不對此發表評論，但我可以告訴你的是，平均 eGFR 斜率仍然保持正值。

And you will -- I know you're very aware that in normal people -- sorry, people without Fabry disease, there's a gradual decline over time in their eGFR. In Fabry patients, there is an exaggerated decline in eGFR that is not fully addressed by ERT and it remains negative in patients that are on ERT.

而且你會 — — 我知道你非常清楚，在正常人中 — — 抱歉，沒有法布瑞氏症的人，他們的 eGFR 會隨著時間的推移而逐漸下降。在法布瑞氏症患者中，eGFR 下降幅度過大，而 ERT 無法完全解決這個問題，並且在接受 ERT 治療的患者中 eGFR 仍然保持負值。

And so as part of our analysis, we'll be looking look at the change from baseline, and we'll be looking at compared to the data for other forms of treatment for Fabry disease. We would not have put out the press release that we did about the eGFR remains positive if we weren't confident that the results were what the agency were looking for.

因此，作為分析的一部分，我們將觀察與基線相比的變化，並將其與法布瑞氏症其他治療形式的數據進行比較。如果我們不確信結果符合該機構的要求，我們就不會發布有關 eGFR 保持陽性的新聞稿。

And that's helpful. Just to wrap up that and clarify my question as well for the statistical analysis plan, even if you're not giving us more detail, you are submitting all the data available from all patients for the BLA submission. But which ones will be used for the -- which ones will be used for the statistical analysis plan? Is it all of them? Or is it just a portion of them?

這很有幫助。總結一下，澄清一下我的問題以及統計分析計劃，即使您沒有向我們提供更多細節，您也會提交所有患者可用的所有數據以供 BLA 提交。但是哪些將用於—哪些將用於統計分析計劃？全部都是嗎？或只是其中的一部分？

It's all of them.

全部都是。

So the submission for the BLA submission will be 32 patients at one year and 19 patients at two years.

因此，BLA 提交的人數為一年 32 名患者和兩年 19 名患者。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

This is Katy on for Luca, and this will be a question on STAC-BBB. And we recall that Homology Medicines had one of the first capsids delivered systematically, which could cross the blood-brain barrier and demonstrated in a mouse model, a dose-dependent reduction in biomarker both systematically and in the CNS. So would you expect to see a similar dual impact with your STAC-BBB capsid? And also, do you expect similar preconditioning to your other capsid approaches, i.e., no prophylactic steroids? Any color there would be very helpful.

我是 Katy，代表 Luca，這將是 STAC-BBB 上的一個問題。我們記得，Homology Medicines 擁有首批系統性遞送的衣殼之一，它可以穿過血腦屏障，並在小鼠模型中證明，系統性和中樞神經系統中的生物標記均呈劑量依賴性減少。那麼，您是否希望看到 STAC-BBB 衣殼產生類似的雙重影響？此外，您是否期望與其他衣殼方法有類似的預處理，即不使用預防性類固醇？任何顏色都會很有幫助。

So we can really only comment on our own capsid and its effectiveness. We have not made the decision whether we will use steroid treatment in the clinical trial yet. We're very pleased with the effectiveness of STAC-BBB. We're very pleased to have seen the result in monkeys across with a variety of cargoes.

所以我們實際上只能評論我們自己的衣殼及其有效性。我們尚未決定是否在臨床試驗中使用類固醇治療。我們對 STAC-BBB 的有效性非常滿意。我們很高興看到猴子運送各種貨物所取得的成果。

And I would really commend you all to look at the presentation that Brian will be giving at ASGCT, where it really showcases both the effectiveness of STAC-BBB and the importance of the right cargo in it.

我真誠地建議大家看看 Brian 在 ASGCT 上所做的演示，其中真正展示了 STAC-BBB 的有效性以及正確貨物的重要性。

And to be honest, that's why it's so pleasing that Lilly, Astellas, and Genentech -- who are all big names in the neuroscience field -- have chosen to license our capsid directly.

老實說，這就是為什麼我們如此高興禮來、安斯泰來和基因泰克——它們都是神經科學領域的大公司——選擇直接授權我們的衣殼。

Yes. And what we will present really is profound survival benefit of the treatment in disease mouse model and sustained brain-wide suppression of prion protein expression in both mouse and nonhuman primate model, supporting its potential as a onetime therapeutic approach for prion disease. So it's very important that we have tested it in NHP and it's extremely well tolerated.

是的。我們真正要展示的是這種治療在疾病小鼠模型中帶來的顯著生存益處，以及在小鼠和非人靈長類動物模型中對朊病毒蛋白表達的持續全腦抑制，支持其作為朊病毒疾病一次性治療方法的潛力。因此，我們在 NHP 中對其進行測試並且其耐受性極好是非常重要的。

And the presidential symposium, I think there's two presentations being given out of something like 4,000 abstracts that were presented. And it's a great credit to the work of Bryan Zeitler and David Ojala and Victoria and Brian's team that have all done so much work to drive something that hopefully next year will be a potential curative -- sorry, a potential treatment for patients with this awful disease.

在總統研討會上，我認為會從大約 4,000 份摘要中進行兩次演講。這要歸功於布萊恩·齊特勒 (Bryan Zeitler)、大衛·奧賈拉 (David Ojala) 以及維多利亞和布萊恩的團隊，他們付出了大量的努力來推動一項新發明，希望明年它能夠成為一種潛在的治療方法——抱歉，是說，為患有這種可怕疾病的患者提供一種潛在的治療手段。

(Operator Instructions)

（操作員指示）

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

I am showing no further questions at this time. And I would like to hand the conference back over to Louise Wilkie for closing remarks.

我目前沒有其他問題。現在我想將會議交還給路易斯·威爾基 (Louise Wilkie) 並請她做最後發言。

Thank you once again for joining us and for your questions today. As a reminder, you can access our presentation on the Investor Relations section of the Sangamo website. We look forward to keeping you updated on our future developments. Thank you.

再次感謝您今天的參與和提問。提醒一下，您可以在 Sangamo 網站的投資者關係部分存取我們的簡報。我們期待向您通報我們未來的發展。謝謝。

This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。祝大家有個愉快的一天。