Sangamo Therapeutics Inc (SGMO) 2024 Q3 法說會逐字稿

Good afternoon and welcome to the Sangamo Therapeutics third-quarter 2024 teleconference call. Please be advised that today's conference is being recorded.

下午好，歡迎參加 Sangamo Therapeutics 2024 年第三季電話會議。請注意，今天的會議正在錄製中。

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.

現在我想將會議交給今天的發言人，投資者關係和企業傳播副總裁路易斯·威爾基 (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; Nathalie Dubois-Stringfellow, Chief Development Officer; and Prathyusha Duraibabu, Chief Financial Officer. Slides from our corporate presentation can be found on our website, sangamo.com, under the presentations page of the investors and media section.

謝謝。大家下午好。感謝您今天加入我們的電話會議。Sangamo 執行領導團隊的幾位成員參加了本次電話會議，包括執行長 Sandy Macrae； Nathalie Dubois-Stringfellow，首席開發長；和財務長 Prathyusha Duraibabu。我們公司演示的幻燈片可以在我們的網站 sangamo.com 的投資者和媒體部分的演示頁面下找到。

This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements related to Sangamo's cash runway; plans to obtain additional capital and ability to continue operating as a going concern; the therapeutic and commercial potential of Sangamo's product candidates and technologies; Sangamo's ability to earn and receive payments from its collaboration and license agreements, including the Genentech and Pfizer agreements; Sangamo's expectations regarding new collaborations and license agreements; the anticipated plans and timelines 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 facts.

本次電話會議包括有關 Sangamo 目前預期的前瞻性陳述。這些報表包括但不限於與 Sangamo 現金跑道相關的報表；計劃獲得額外資本和持續經營能力； Sangamo 候選產品和技術的治療和商業潛力； Sangamo 透過其合作和許可協議（包括基因泰克和輝瑞協議）賺取和接收付款的能力； Sangamo 對新合作和授權協議的期望； Sangamo 及其合作者的臨床試驗預期計劃和時間表；臨床數據演示和發布、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, 2023, as supplemented by Sangamo's quarterly report on Form 10-Q for the quarter ending September 30, 2024, and subsequent filings and reports that Sangamo makes from time to time with the SEC.

實際結果可能與我們今天討論的結果大不相同。這些聲明受到我們向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2023 年12 月31 日的財年的10-K 表格年度報告中，並由Sangamo 的10 -Q 表格季度報告進行了補充截至 2024 年 9 月 30 日的季度，以及 Sangamo 不時向 SEC 提交的後續文件和報告。

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. Please note that all forward-looking statements about our future plans and expectations are subject to our ability to secure adequate additional funding.

今天所述的前瞻性陳述是自今天起作出的，我們不承擔更新此類資訊的義務，除非法律要求。請注意，有關我們未來計劃和期望的所有前瞻性陳述均取決於我們獲得足夠額外資金的能力。

Now I'll turn the call over to our CEO, Sandy Macrae.

現在我將把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 today. As we near the end of 2024, I'm extremely proud of the progress we are making this year. We are committed to translating groundbreaking science into medicines that transform the lives of patients and families afflicted with serious neurological diseases.

謝謝你，路易斯，今天參加電話會議的每個人都下午好。2024 年即將結束，我對我們今年的進展感到非常自豪。我們致力於將突破性的科學轉化為藥物，改變患有嚴重神經系統疾病的患者和家庭的生活。

The updates we will share today demonstrate several meaningful advances towards that goal and show how we believe Sangamo is well positioned for continued progress. First, Sangamo has transformed from a Phase 1/2 company to a pre-BLA company as a result of significant regulatory developments in our Fabry disease program.

我們今天將分享的最新動態展示了朝著這一目標取得的幾項有意義的進展，並表明我們相信 Sangamo 已做好持續進展的準備。首先，由於我們法布瑞氏症計畫監管方面的重大進展，Sangamo 已從 1/2 期公司轉變為 BLA 前公司。

Second, Pfizer continues to engage in discussions with regulatory authorities concerning our hemophilia A program, both of which have the potential to provide a long-term financial foundation for our core neurology pipeline. Third, we signed a neurology epigenetic regulation and capsid delivery license agreement with Genentech and received $50 million in upfront license fees and milestone payments. And finally, we submitted our first ever IND application for a neurology indication.

其次，輝瑞繼續與監管機構就我們的血友病 A 計畫進行討論，這兩項計畫都有可能為我們的核心神經學管道提供長期的財務基礎。第三，我們與 Genentech 簽署了神經學表觀遺傳調控和衣殼遞送許可協議，並獲得了 5,000 萬美元的預付款許可費和里程碑付款。最後，我們提交了第一份針對神經病學適應症的 IND 申請。

These developments demonstrate that Sangamo is steadily executing upon our strategy, is driving potential medicines towards patients in need and is continuing to advance plans to put the company on a more stable financial footing. Nathalie will share more context in a moment, but I want to start out by highlighting the significant clinical and regulatory progress made this quarter in our Fabry disease program, following alignment with the FDA on a clear regulatory pathway to accelerated approval.

這些進展表明 Sangamo 正在穩步執行我們的策略，正在將潛在的藥物推向有需要的患者，並繼續推進計劃，使公司的財務基礎更加穩定。Nathalie 稍後將分享更多背景信息，但我想首先強調本季度我們的法布瑞氏症計畫在與 FDA 就加速批准的明確監管途徑達成一致後取得的重大臨床和監管進展。

This pathway reduces the time to potential approval by three years and avoids the requirement for an additional lengthy and costly registrational study, which is incredibly impactful given the unmet medical need for patients with Fabry disease. We are delighted to have such a clear regulatory pathway that could bring this treatment to patients significantly sooner than originally anticipated and have begun to execute BLA readiness activities ahead of a submission anticipated in the second half of 2025.

該途徑將潛在批准的時間縮短了三年，並避免了額外漫長且昂貴的註冊研究的需要，考慮到法布瑞氏症患者未得到滿足的醫療需求，這具有難以置信的影響力。我們很高興擁有如此清晰的監管途徑，可以比最初預期更快地為患者提供這種治療方法，並已開始在預計於 2025 年下半年提交之前執行 BLA 準備活動。

As you can imagine, this announcement has generated a lot of interest from external stakeholders, including patients who tell us about the remarkable change our treatment has brought to their lives, investors and potential strategic partners. We continue to engage in ongoing business development discussions as we seek to get this treatment to patients as quickly as possible.

正如您可以想像的那樣，這項公告引起了外部利害關係人的極大興趣，包括告訴我們我們的治療為他們的生活帶來顯著變化的患者、投資者和潛在的策略合作夥伴。我們將繼續參與正在進行的業務開發討論，尋求盡快為患者提供這種治療方法。

Following the recent top-line readout from Pfizer for the Phase 3 AFFINE trial in hemophilia A, we also moved closer to potential regulatory submissions for this program, which has the potential to unlock up to $220 million in regulatory and commercial milestones for Sangamo over the next two years.

繼輝瑞最近公佈A 型血友病3 期AFFINE 試驗的頂線數據後，我們也更接近該項目的潛在監管提交，該項目有可能在未來一段時間內為Sangamo 帶來高達2.2 億美元的監管和商業里程碑。

Pfizer will present a detailed Phase 3 data update at the upcoming American Society for Hematology or ASH Annual Meeting in December. And Pfizer have advised us that they are discussing this data with regulatory authorities, which is very encouraging. Taken together, the Fabry and hemophilia A programs could provide Sangamo with a solid and long-term financial foundation for our core neurology pipeline.

輝瑞將在 12 月即將舉行的美國血液學會或 ASH 年會上公佈詳細的 3 期數據更新。輝瑞告訴我們，他們正在與監管機構討論這些數據，這是非常令人鼓舞的。總而言之，Fabry 和 A 型血友病計畫可以為 Sangamo 的核心神經病學管道提供堅實且長期的財務基礎。

We are thrilled to be in the enviable position of seeing up to two potential BLA submissions in 2025 for product candidates developed by Sangamo, each of which leverage the best of our science and capabilities and address significant unmet patient needs and commercial opportunities. This exciting momentum propels our neurology pipeline forward as we work to advance our science and technology for neurological indications.

我們很高興能夠在2025 年看到Sangamo 開發的候選產品最多有兩項潛在的BLA 提交，每一項都充分利用了我們最好的科學和能力，並解決了未滿足的重大患者需求和商業機會。隨著我們努力推進神經系統適應症的科學和技術，這種令人興奮的勢頭推動我們的神經病學管道向前發展。

This quarter, we signed our first neurology epigenetic regulation and capsid delivery license agreement. We have granted Genentech an exclusive license to our highly potent zinc finger repressors that are directed to tau, a critical gene involved in Alzheimer's disease and other tauopathies as well as an additional undisclosed second neurology target. For these same targets, we also granted Genentech an exclusive license to our industry-leading neurotropic delivery capsid STAC-BBB, which has demonstrated potent blood-brain barrier penetration and brain transduction in nonhuman primates.

本季度，我們簽署了第一份神經學表觀遺傳調控和衣殼交付許可協議。我們已向基因泰克授予我們高效鋅指阻遏物的獨家許可，該阻遏物針對tau，這是一種與阿茲海默症和其他tau 病相關的關鍵基因，也是一個未公開的第二個神經病學靶點。對於這些相同的目標，我們還向基因泰克授予了我們行業領先的神經營養遞送衣殼STAC-BBB 的獨家許可，該衣殼已在非人類靈長類動物中證明了有效的血腦屏障穿透和腦轉導作用。

We have received $50 million in upfront license fees and milestone payments from Genentech, which extended our cash runway to allow us to continue advancing other ongoing business development activities. This agreement has further drawn interest in our science and enhanced our ability to attract new potentially valuable partnerships.

我們已從 Genentech 收到了 5000 萬美元的預付款許可費和里程碑付款，這擴大了我們的現金跑道，使我們能夠繼續推進其他正在進行的業務開發活動。該協議進一步引起了人們對我們科學的興趣，並增強了我們吸引新的潛在有價值合作夥伴的能力。

We are currently advancing business development discussions with additional potential collaborators seeking to license our novel intravenous capsid, STAC-BBB, and we believe this capsid is a potentially valuable source of additional non-dilutive funding.

我們目前正在與其他潛在合作者推進業務開發討論，尋求獲得我們新型靜脈注射衣殼 STAC-BBB 的許可，我們相信這種衣殼是額外非稀釋性資金的潛在有價值來源。

This quarter, we also submitted our first ever IND application for a neurology indication. We expect our lead program, ST-503 for intractable pain to advance into the clinic in the middle of 2025, assuming clearance of the IND with the FDA with our expected prion clinical trial authorization submission followed close behind by the end of 2025.

本季度，我們也提交了首個神經病學適應症 IND 申請。我們預計我們用於治療頑固性疼痛的主導項目 ST-503 將在 2025 年中期進入臨床，假設 IND 獲得 FDA 批准，我們預期的朊病毒臨床試驗授權提交緊隨其後，並在 2025 年底提交。

Our cash runway remains unchanged and is sufficient to fund our planned operations into the first quarter of 2025, absent any potential funding from a Fabry partnership, hemophilia A milestone payments from Pfizer or additional STAC-BBB collaboration agreements. Alongside the two anticipated BLA submissions next year, we see a viable path to financial stability.

我們的現金跑道保持不變，足以為我們到2025 年第一季的計劃運營提供資金，如果沒有來自Fabry 合作夥伴的任何潛在資金、輝瑞的血友病A 里程碑付款或額外的STAC-BBB 合作協議。除了明年預計提交的兩份 BLA 之外，我們還看到了實現金融穩定的可行途徑。

I would now like to hand it over to Nathalie, our Head of Development, who will share additional context and also take us through other pipeline updates. Nathalie?

我現在想將其交給我們的開發主管 Nathalie，她將分享更多背景信息，並引導我們完成其他管道更新。娜塔莉？

Thank you, Sandy. Beginning first with Fabry, we were excited to announce last late month that we have aligned on a clear regulatory pathway to accelerated approval with the FDA for isaralgagene civaparvovec or ST-920, our wholly owned gene therapy candidate for the treatment of Fabry disease.

謝謝你，桑迪。首先從Fabry 開始，我們很高興地在上個月末宣布，我們已經制定了明確的監管途徑，以加速FDA 批准isargagene civaparvovec 或ST-920，這是我們全資擁有的用於治療Fabry 病的基因療法候選藥物。

The FDA has confirmed that estimated glomerular filtration rate or eGFR slope data at 52 weeks from all patients in the ongoing Phase 1/2 STAR study can serve as the primary basis for approval under the accelerated approval pathway. This pathway avoids the requirement for an additional costly registrational study as we had previously anticipated and importantly, accelerates the estimated time to potential approval by approximately three years.

FDA 已確認，正在進行的 1/2 期 STAR 研究中所有患者的 52 週估計腎小球濾過率或 eGFR 斜率數據可以作為加速批准途徑下批准的主要依據。該途徑避免了我們先前預期的額外昂貴的註冊研究的要求，而且重要的是，將潛在批准的預計時間加快了大約三年。

Sangamo engaged with the FDA on alternative pathway to potential approval following analysis of clinical data from the Phase 1/2 STAR study showing encouraging safety and efficacy data.

在對 1/2 期 STAR 研究的臨床數據進行分析後，Sangamo 與 FDA 合作尋找潛在批准的替代途徑，該研究顯示出令人鼓舞的安全性和有效性數據。

Renal manifestation such as proteinuria or decreased estimated glomerular filtration rate, or eGFR, occur early in life in almost all male and in many female patients with Fabry disease and can lead to end-stage renal disease and early death.

幾乎所有患有法布瑞氏症的男性和許多女性患者都會在生命早期出現蛋白尿或估計腎小球濾過率 (eGFR) 降低等腎臟表現，並可能導致終末期腎病和過早死亡。

EGFR is assessed in millimeter of cleansed blood per minute per body surface. For context, the average untreated patient has an eGFR slope of minus 5.6. However, in the 18 male and female patients treated with isaralgagene civaparvovec with more than one year of follow-up data, we observed a statistically significant positive mean annualized eGFR slope.

EGFR 以每個身體表面每分鐘淨化血液的毫米數進行評估。就上下文而言，未經治療的患者的 eGFR 斜率平均為負 5.6。然而，在 18 名接受 isargagene civaparvovec 治療的男性和女性患者中，有一年多的追蹤數據，我們觀察到平均年化 eGFR 斜率具有統計學意義的正值。

Generating a positive eGFR slope is a truly remarkable achievement for Fabry patients, especially since other Fabry therapies according to public data, improve eGFR value compared to untreated Fabry patients, but still show a negative overall eGFR slope. Based on this latest data, the FDA agreed that eGFR slope at 52 weeks can serve as an intermediate clinical endpoint to support a potential accelerated approval.

對於法布瑞氏症患者來說，產生正的eGFR 斜率確實是一項了不起的成就，特別是因為根據公開數據，與未經治療的法布瑞氏症患者相比，其他法布瑞氏療法改善了eGFR 值，但總體eGFR 斜率仍為負。根據這項最新數據，FDA 同意 52 週時的 eGFR 斜率可以作為中間臨床終點，以支持潛在的加速批准。

The FDA also advised that eGFR slope at 104 weeks may be assessed to verify clinical benefits. The complete data set to support the accelerated approval pathway will be available in the first half of next year, unlocking a potential BLA submission in the second half of 2025, three years ahead of previous estimates. We are delighted to have a clear regulatory pathway that could bring this treatment to patients in need significantly sooner than originally anticipated.

FDA 也建議可以評估 104 週時的 eGFR 斜率，以驗證臨床益處。支援加速審批途徑的完整資料集將於明年上半年提供，預計在 2025 年下半年提交 BLA，比之前的估計提前了三年。我們很高興有一個明確的監管途徑，可以比最初預期更快地將這種治療方法帶給有需要的患者。

Fabry is a debilitating disease for which there is a serious unmet medical need and this need was clear at the National Fabry Disease Foundation Patient Conference held in October, at which Sangamo was in attendance. During focus group discussions, Fabry patient elaborated on the challenges associated with current treatment option, including having to switch treatment regimen due to unwanted side effect, insufficient resolution of their symptom and breakthrough pain.

法布瑞氏症是一種使人衰弱的疾病，其醫療需求嚴重未得到滿足，這一需求在10 月舉行的國家法布瑞氏症基金會患者會議上得到了明確體現，桑加莫也出席了這次會議。在焦點小組討論中，法布瑞氏症患者詳細闡述了與目前治療方案相關的挑戰，包括因不良副作用、症狀緩解不足和突發性疼痛而不得不改變治療方案。

Patients also noted the challenges of receiving long infusion every second week, which is logistically problematic and at time can cause them to skip doses. As a reminder, our Phase 1/2 STAR study has enrolled and dosed 33 patients, representing a broad range of Fabry patients. We have patients who were on ERT at the start of the study as well as patients who were ERT-naive or pseudo-naive. We have male and female patients as well as those with cardiac or renal implication.

患者還指出了每兩週接受長時間輸注的挑戰，這在邏輯上存在問題，有時可能會導致他們跳過劑量。提醒一下，我們的 1/2 期 STAR 研究已入組 33 名患者並對其進行了給藥，代表了廣泛的 Fabry 患者。我們有在研究開始時接受 ERT 的患者，以及未接受 ERT 或假性接受 ERT 的患者。我們有男性和女性患者以及患有心臟或腎臟問題的患者。

With the positive annualized eGFR slope observed thus far across these different types of Fabry patients, we anticipate that the BLA submission will cover the entirety of the Fabry population aged 18 years and older. In the other STAR study update, all 18 patients who started the study on ERT are now successfully off ERT and the first patient has been withdrawn from ERT recently achieved an impressive three years of ERT. That is a significant achievement.

鑑於迄今為止在這些不同類型的 Fabry 患者中觀察到的正年化 eGFR 斜率，我們預計 BLA 提交將涵蓋所有 18 歲及以上的 Fabry 族群。在另一項 STAR 研究更新中，所有 18 名開始 ERT 研究的患者現已成功退出 ERT，並且第一位退出 ERT 的患者最近取得了令人印象深刻的三年 ERT。這是一項重大成就。

More broadly, with the longest treated ST-920 patient recently achieving four years of follow-up, our data continue to look encouraging with all patients achieving and maintaining physiological or supraphysiological level of plasma alpha-Gal A enzyme activity to date.

更廣泛地說，隨著治療時間最長的ST-920 患者最近完成了四年的隨訪，我們的數據仍然令人鼓舞，迄今為止所有患者都達到並維持了血漿α-Gal A 酶活性的生理或超生理水平。

In terms of next step, we have begun to execute BLA readiness activity and continue to advance ongoing business development discussions with potential collaboration partners.

下一步，我們已經開始執行 BLA 準備活動，並繼續推進與潛在合作夥伴正在進行的業務開發討論。

We are also committed to working with the European Medicines Agency, or EMA, to identify the optimal regular path forward in Europe and following a successful PRIME kickoff earlier this year, are preparing for continued discussions. Our hope is to be able to arrive at an aligned approach across the regulatory agencies and we anticipate sharing a regulatory update in early 2025.

我們也致力於與歐洲藥品管理局 (EMA) 合作，確定歐洲的最佳常規發展路徑，並在今年稍早成功啟動 PRIME 後，正在準備繼續討論。我們希望監管機構能夠達成一致的方法，並預計在 2025 年初分享監管更新。

Moving now to giroctocogene fitelparvovec, an investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A. On December 9, Pfizer plans to present detailed data from the Phase 3 AFFINE trial in an oral presentation at the 66th ASH Annual Meeting and Exposition.

現在轉向giroctocogene fitelparvovec，這是我們正在與輝瑞合作開發的研究性基因療法，用於治療中重度至重度A 型血友病患者。的口頭報告中展示3 期AFFINE 試驗的詳細數據會議和博覽會。

The ASH abstract, which was released last week, confirmed that the AFFINE trial met its primary endpoint of non-inferiority and superiority with a statistically significant decrease in total annualized bleeding rate, or ABR, from week 12 to at least 15 months of follow-up post infusion compared with routine factor VIII replacement prophylaxis treatment.

上週發布的ASH 摘要證實，AFFINE 試驗達到了非劣效性和優越性的主要終點，從第12 周到至少15 個月的隨訪，年化總出血率(ABR) 出現了統計學上的顯著下降。

Key secondary endpoint as defined by the trial protocol, the percentage of participants with factor VIII activity greater than 5% at 15 months or ABR for treated bleed were met and also demonstrated superiority compared to prophylaxis. Notably, giroctocogene fitelparvovec was generally well tolerated with no study discontinuations. These data further validate our effort to discover and develop genomic medicine with the potential to improve the lives of patients.

試驗方案中定義的關鍵次要終點，即 15 個月時因子 VIII 活性大於 5% 或治療出血的 ABR 的參與者百分比得到滿足，並且與預防相比也表現出優越性。值得注意的是，giroctocogene fitelparvovec 通常具有良好的耐受性，沒有中斷研究。這些數據進一步驗證了我們在發現和開發具有改善患者生活潛力的基因組醫學方面所做的努力。

Partnering with an organization with strong commercialization infrastructure and experience as well as a broader franchise in this area was important to us as we enter into hemophilia A partnership with Pfizer. We greatly appreciate Pfizer's leadership of this important program.

當我們與輝瑞建立血友病 A 合作夥伴關係時，與一個在該領域擁有強大商業化基礎設施和經驗以及更廣泛特許經營權的組織合作對我們來說非常重要。我們非常感謝輝瑞公司對這項重要計畫的領導。

Pfizer has advised us that they are discussing the Phase 3 AFFINE data with regulatory authorities. As a reminder, we are eligible to earn up to $220 million in milestone payment from Pfizer upon the achievement of certain regulatory and commercial milestones and 14% to 20% royalty on potential sales from this program, if approved and commercialized. These important advances allows us to focus on our core mission to treat debilitating neurological disorders with innovative genomic medicines.

輝瑞告知我們，他們正在與監管機構討論 AFFINE 3 期數據。提醒一下，在實現某些監管和商業里程碑後，我們有資格從輝瑞獲得高達2.2 億美元的里程碑付款，如果獲得批准並商業化，我們還可以從該計劃的潛在銷售中獲得14% 至20%的特許權使用費。這些重要進展使我們能夠專注於我們的核心使命，即用創新的基因組藥物治療衰弱性神經系統疾病。

We believe our ability to combine potent zinc finger epigenetic regulation payloads with exciting new industry-leading capsid delivery technology could unlock the potential of our neurology pipeline and change the treatment paradigm for neurological indications for which delivery of treatment to the central nervous system has historically been challenging. This quarter, we submitted an IND application to the FDA for our Nav1.7 program or ST-503 for the treatment of intractable pain.

我們相信，我們將有效的鋅指表觀遺傳調控有效負載與令人興奮的行業領先的新衣殼遞送技術相結合的能力可以釋放我們神經病學管道的潛力，並改變神經系統適應症的治療範式，而神經系統適應症的治療歷來是針對中樞神經系統的。本季度，我們向 FDA 提交了 Nav1.7 計畫或 ST-503 用於治療頑固性疼痛的 IND 申請。

Neuropathic pain can be caused by a broad array of pathologies impacting the central or peripheral nervous system. such as surgical trauma, spinal cord injury, nerve compression, neurological and infectious diseases or metabolic and hereditary syndromes. ST-503 is not intended for sporadic or acute pain like a toothache or bunionectomy, but for intractable chronic pain that completely dominates and often destroys the life of patients over many years.

神經性疼痛可由影響中樞或週邊神經系統的多種病理引起。例如手術創傷、脊髓損傷、神經受壓、神經系統和傳染病或代謝和遺傳綜合症。ST-503並非用於治療牙痛或拇囊炎切除術等偶發性或急性疼痛，而是用於治療多年來完全主導並經常破壞患者生活的頑固性慢性疼痛。

Assuming FDA clearance of the IND, the Phase 1/2 study will assess the effectiveness of ST-503 in addressing idiopathic small fiber neuropathy, or ISFN, a peripheral neuropathy that results in highly debilitating syndromes of burning, prickling, stabbing or lightning-like pain. ISFN has an estimated prevalence of at least 43,000 patients in the US and more broadly, peripheral neuropathy are estimated to affect nearly 40 million Americans.

假設FDA 批准IND，1/2 期研究將評估ST-503 在解決特發性小纖維神經病變（ISFN）方面的有效性，ISFN 是一種週邊神經病變，可導致燒傷、刺痛、刺傷或閃電樣高度衰弱綜合症疼痛。據估計，ISFN 在美國至少有 43,000 名患者患病，更廣泛地說，周圍神經病變估計影響近 4000 萬美國人。

Antidepression, anticonvulsant, opioid or topical therapy can be tried, although no long-lasting or curative therapy are currently available for ISFN patients, leading to a high unmet medical need for this patient population. A significant body of evidence implicates sodium channels in mediating the pathophysiology of neuropathic pain.

可以嘗試抗憂鬱、抗驚厥、鴉片類藥物或局部治療，但目前 ISFN 患者尚無持久或治癒性治療，導致該患者族群的醫療需求未被滿足。大量證據顯示鈉通道介導神經性疼痛的病理生理學。

ST-503 use an adeno-associated virus or AAV vector carrying an engineered zinc finger repressor to specifically target the human gene SCN9A that encodes the Nav1.7 channel -- sodium channel and is critical for pain signaling. Developing small molecules that specifically target Nav1.7 is challenging due to the high structural similarity between different sodium channels, making it difficult to achieve selectivity and avoid off-target effects.

ST-503 使用攜帶工程化鋅指阻遏物的腺相關病毒或 AAV 載體，專門針對編碼 Nav1.7 通道（鈉通道）的人類基因 SCN9A，該基因對疼痛信號傳導至關重要。由於不同鈉通道之間的結構高度相似，開發專門針對 Nav1.7 的小分子具有挑戰性，因此很難實現選擇性並避免脫靶效應。

By directly targeting the SCN9A gene, ST-503 was shown to selectively reduce the expression of 1.7 sodium channels in sensory neurons in animal model and significantly reduce hypersensitivity following a single intrathecal administration.

透過直接靶向 SCN9A 基因，ST-503 在動物模型中選擇性降低感覺神經元中 1.7 鈉通道的表達，並在單次鞘內給藥後顯著降低超敏反應。

Sangamo's preclinical research has shown ST-503 to be well tolerated in nonhuman primate and substantial Nav1.7 reduction was observed with no off-target effects. This preclinical data, which demonstrate the potential of ST-503 as a therapy for chronic neuropathic pain, are elaborated upon in more detail in a manuscript published in BioArchive earlier this quarter, which is also available on the presentations and publications section of our investor page on sangamo.com. We expect to start the Phase 1/2 in the middle of 2025. This represents a transformational step forward for Sangamo as the first of our neurology program to progress to the clinic.

Sangamo 的臨床前研究表明 ST-503 在非人靈長類動物中具有良好的耐受性，並且觀察到 Nav1.7 大幅降低且沒有脫靶效應。這些臨床前數據證明了ST-503 作為慢性神經性疼痛療法的潛力，本季早些時候在BioArchive 上發表的一份手稿中對此進行了更詳細的闡述，該手稿也可以在我們投資者頁面的演示和出版物部分找到在 sangamo.com 上。我們預計將於 2025 年中期啟動 1/2 階段。作為我們第一個進入臨床的神經病學項目，這代表著 Sangamo 向前邁出了變革性的一步。

It is hoped that if efficacy is demonstrated, the application of ST-503 could be broadened to patient population suffering from other types of chronic neuropathic pain. Moving now to prion, clinical trial authorization, or CTA, enabling activities continue to advance for our program to treat prion disease, which leverage our novel STAC-BBB capsid. As a reminder, prion disease represents a group of conditions with a devastating unmet medical need, which we believe our technology can address.

希望如果療效得到證實，ST-503的應用可以擴大到患有其他類型慢性神經性疼痛的患者族群。現在轉向朊病毒、臨床試驗授權或 CTA，使我們利用我們的新型 STAC-BBB 衣殼治療朊病毒疾病的計劃繼續取得進展。提醒一下，朊病毒病代表了一組具有毀滅性的未滿足醫療需求的疾病，我們相信我們的技術可以解決這些問題。

With more than 1,500 new patients diagnosed each year across the US and Europe, this is a disease that is rapidly progressing and always fatal, usually within 12 to 15 months of symptom onset and with no currently effective treatment option available.

美國和歐洲每年診斷出超過 1,500 名新患者，這是一種進展迅速且總是致命的疾病，通常在症狀出現後 12 至 15 個月內出現，且目前尚無有效的治療選擇。

In October, we presented updated data at the Prion 2024 Conference, which demonstrated the potency of our zinc finger repressor in a disease mouse model at multiple dose levels. The zinc finger repressor significantly reduced expression of prion mRNA and protein in the brain, extended mouse survival and limited the formation of toxic prion aggregates.

10 月，我們在 Prion 2024 會議上展示了更新的數據，證明了我們的鋅指阻遏物在多個劑量水平的疾病小鼠模型中的效力。鋅指阻遏物顯著降低了大腦中朊病毒mRNA和蛋白質的表達，延長了小鼠的存活時間並限制了有毒朊病毒聚集體的形成。

Additionally, nonhuman primate data at Prion 2024 highlighted that a single intravenous administration of the prion zinc finger repressor delivered via STAC-BBB resulted in potent and widespread repression of the prion gene in transduced neuron. A CTA submission for this program is expected in the fourth quarter of 2025. I will now hand it back to Sandy for closing remarks.

此外，Prion 2024 上的非人靈長類動物數據強調，透過 STAC-BBB 遞送的朊病毒鋅指抑制物單次靜脈注射可導致轉導神經元中朊病毒基因的有效和廣泛抑制。該計劃的 CTA 預計將於 2025 年第四季提交。現在我將把它交還給桑迪以供結束語。

Thank you, Nathalie. In closing, we are delighted with the momentum being generated this year and are committed to the continued advancement of both our wholly owned and partnered programs. In 2025, Sangamo science could lead to BLA submissions for up to two separate gene therapy programs that we believe have the potential to fund the neurology company in the long term.

謝謝你，娜塔莉。最後，我們對今年產生的勢頭感到高興，並致力於繼續推進我們的全資和合作項目。到 2025 年，Sangamo science 可能會向 BLA 提交最多兩個獨立的基因治療項目，我們相信這些項目有可能為這家神經病學公司提供長期資金。

We plan to dose patients our first-ever neurology epigenetic regulation study. And we plan to submit an IND for the second study, which would be the first-in-human study of our novel proprietary STAC-BBB neurotropic capsid.

我們計劃對患者進行首次神經學表觀遺傳調控研究。我們計劃提交第二項研究的 IND，這將是我們新型專利 STAC-BBB 神經性衣殼的首次人體研究。

We are also currently engaged in advanced business development discussions for our new potential STAC-BBB collaborations. This is remarkable progress for a company of our size. We are pleased to have delivered these milestones in 2024 and plan to continue executing on our strategy in the coming months as we complete the task of transforming Sangamo into a neurology genomic medicine company.

我們目前也正在就我們新的潛在 STAC-BBB 合作進行高級業務開發討論。對於我們這樣規模的公司來說，這是一個了不起的進步。我們很高興在 2024 年實現了這些里程碑，並計劃在未來幾個月內繼續執行我們的策略，完成將 Sangamo 轉變為神經基因組醫學公司的任務。

We see an exciting future as we make progress in addressing our long-term financing needs and look forward to building upon this year's progress in 2025 as we further advance our therapies to patients in need. Operator, please open the line for questions.

隨著我們在解決長期融資需求方面取得進展，我們看到了令人興奮的未來，並期待在 2025 年以今年的進展為基礎，進一步為有需要的患者提供治療方案。接線員，請開通提問線。

(Operator Instructions) Gena Wang, Barclays.

（操作員指示）Gena Wang，巴克萊銀行。

Congrats on multiple achievements here. So maybe I'll just focusing on Fabry program. Two related questions. The first one is regarding the FDA comments that eGFR slope at 52 weeks can serve as intermediate and clinical endpoint. Does that mean FDA wanted to see statistic significance of the end of the 52 eGFR compared to the baseline?

在此祝賀您取得多項成就。所以也許我會只關注法布里程序。兩個相關問題。第一個是關於 FDA 的評論，即 52 週時的 eGFR 斜率可以作為中間和臨床終點。這是否意味著 FDA 希望了解 52 eGFR 末端與基線相比的統計顯著性？

And then eGFR slope at the 104 weeks may be assessed to verify clinical benefit. Can you elaborate what does that mean? Do you need to continue to show statistics significant benefit compared to baseline? Or do you need to show positive trend continue at the 104 weeks?

然後可以評估 104 週時的 eGFR 斜率以驗證臨床益處。能詳細說明一下這是什麼意思嗎？您是否需要繼續顯示統計數據與基線相比的顯著優勢？或者你需要在104週繼續表現出正面的趨勢嗎？

And the second question is related to the strategy. I think, Sandy, you mentioned, I think that that has been a while that you wanted to -- seeking partnership for this program. And now given the latest update, what is your latest thinking regarding this program that you think it will be most value generative for the shareholders? So would that be keep in-house or seeking partnership? If seeking partnership, what kind of evaluation you will be looking for?

第二個問題與策略有關。我想，桑迪，你提到過，我想你已經有一段時間想要為這個項目尋求合作夥伴了。現在鑑於最新的更新，您對此計劃的最新想法是什麼？那麼，是繼續留在公司內部還是尋求合作夥伴呢？如果尋求合作夥伴，您會尋求什麼樣的評估？

Thank you, Gena, for the questions. So I'm going to pass on to Nathalie. We haven't given details of the statistical analysis that the agency have asked us to do. It really is incredible that the eGFR is shown to be a positive slope and also that the agency has embraced this and agreed to accelerated approval at one year. Nathalie, can you add some color to this?

謝謝吉納提出的問題。所以我要轉告娜塔莉。我們尚未提供該機構要求我們進行的統計分析的詳細資訊。令人難以置信的是，eGFR 顯示為正斜率，而該機構已經接受了這一點並同意在一年內加速批准。娜塔莉，你能為這個添加一些顏色嗎？

Yes. Thank you. Yes, we're delighted to have a clear regulatory pathway to accelerated approval that could bring this drug sooner to the patient. So the FDA has agreed that the data can serve as the primary -- at 52 weeks can serve as the primary basis for approval under the accelerated approval program using the eGFR slope at 52 weeks across all patients. And this is an intermediate clinical endpoint that will give us accelerated approval.

是的。謝謝。是的，我們很高興有一個明確的監管途徑來加速批准，可以更快地將這種藥物帶給病人。因此 FDA 同意這些數據可以作為主要數據——52 週時的數據可以作為加速批准計劃下批准的主要依據，使用所有患者 52 週時的 eGFR 斜率。這是一個中間臨床終點，將使我們加速批准。

And just as a reminder, there is no limitation placed on biologic product granted accelerated approval. In addition, the FDA indicated that the data from the 104 weeks can use to confirm clinical benefit. So we see that there is no need for any additional study. And we will have those discussions during the pre-BLA meeting with the FDA. But we anticipate that we will present the two-year data for the 32 patient in 2026 for full approval.

提醒一下，加速核准的生物產品沒有任何限制。此外，FDA表示，104週的數據可以用來確認臨床效益。所以我們看到沒有必要進行任何額外的研究。我們將在 BLA 前與 FDA 的會議期間進行這些討論。但我們預計將在 2026 年提供 32 名患者的兩年數據以獲得完全批准。

Yes, Gena, this is quite important to get clear because I know that a number of people conflate accelerated approval with a confirmatory study. I want to be absolutely clear that no confirmatory study has been asked for or is required. We will submit the data for the one year, at which point there will be 32 at one year, but also 19 of them will already have reached their two-year point.

是的，Gena，弄清楚這一點非常重要，因為我知道很多人將加速批准與驗證性研究混為一談。我想絕對明確的是，沒有要求或不需要任何驗證性研究。我們將提交一年的數據，屆時一年的數據將有32個，但其中19個已經達到了兩年的數據。

We anticipate that we would be submitting the full two-year data set a year later. The agency has said that they would recommend looking at this as confirmation of the one-year data.

我們預計我們將在一年後提交完整的兩年資料集。該機構表示，他們建議將此視為一年數據的確認。

What's been really interesting is when we've looked at the patients that have reached two years already is that the one-year predicts the two-year data. So the patients are positive at one year, it predicts that they'll also be positive at two-year. So this is exciting for Sangamo because all of a sudden, the BLA filing has been pulled in three years. We're doing everything possible to drive this forward to make sure we get it to patients with a filing in the second half of next year.

真正有趣的是，當我們觀察已經達到兩年的患者時，一年的數據可以預測兩年的數據。因此，患者在一年時呈陽性，預計在兩年時也會呈現陽性。因此，這對 Sangamo 來說是令人興奮的，因為 BLA 申請突然在三年內被撤回。我們正在盡一切可能推動這一進程，以確保我們能夠在明年下半年將其提交給患者。

As to your other question about partnerships, as you can imagine, there's a number of people have been very interested in these results. It's wonderful when we can announce a partnership around a quarterly call. Unfortunately, these things just take time and we've almost had to refresh the partnership discussions with this new data. We hope to be able to share more about it in the near future.

至於你關於合作關係的其他問題，正如你可以想像的那樣，有很多人對這些結果非常感興趣。當我們能夠在季度電話會議上宣佈建立合作夥伴關係時，真是太棒了。不幸的是，這些事情需要時間，我們幾乎不得不用這些新數據刷新合作夥伴關係討論。我們希望能夠在不久的將來分享更多相關資訊。

But what we want to do is make sure we do a deal that gets it to patients with a filing in the second half of next year and a launch sometime in the first half of '26. I hope that answers your question.

但我們想要做的是確保我們達成協議，在明年下半年向患者提供該藥物，並在 26 年上半年的某個時候推出。我希望這能回答你的問題。

Yanan Zhu, Wells Fargo.

朱亞楠，富國銀行。

This is [Kwan] on for Yanan. So our questions are also around the Fabry program. Can you share with us when may we see next data update from the program?

這是延安的[關]。所以我們的問題也是圍繞著法布里來規劃的。您能否與我們分享我們何時可以看到該計劃的下一次數據更新？

Nathalie?

娜塔莉？

Yes. So now our Phase 1/2 has become a registrational study. So we are being very careful about disclosing the details of the data. And we expect to have the data in the second quarter of 2025 and share at that time the top-line data.

是的。所以現在我們的1/2期已經成為註冊研究。因此，我們在披露數據細節時非常謹慎。我們預計將在 2025 年第二季獲得數據，並分享當時的頂線數據。

So to be clear, the last patient joined this study in April of this year. The last patient last visit will be April of next year. It then takes some period of time to clean the data and that will allow us to submit the data in the second half of next year. Once we have that data cleaned and prepared, we will look for the best opportunity to share the data with all of you.

需要明確的是，最後一位患者是在今年四月加入這項研究的。最後一位患者的最後一次就診將是明年四月。然後需要一段時間來清理數據，這樣我們就可以在明年下半年提交數據。一旦我們清理和準備好數據，我們將尋找與大家分享數據的最佳機會。

Got it. And some quick follow-up. So for patients with longer follow-up, you mentioned that they still have a positive eGFR slope. But do you see any change in the slope when patients' follow-ups get longer? And also in the ERT patients, do you see any change in the eGFR slope when patients stop -- withdraw their ERT?

知道了。以及一些快速跟進。因此，對於追蹤時間較長的患者，您提到他們的 eGFR 斜率仍然為正。但是，當患者的追蹤時間延長時，您是否發現斜率有任何變化？另外，在 ERT 患者中，當患者停止（撤回 ERT）時，您是否發現 eGFR 斜率有任何變化？

So there are so many questions that I'm sure we would all like to discuss about this data and we look forward to sharing it at the right time. What I can say is the longest-lasting patient in the study is over four years and four months. And those are the patients who are in the lowest dose of the dose escalation study and they're doing very well.

因此，有很多問題，我相信我們都想討論這些數據，並期待在正確的時間分享它。我可以說的是，研究中存活時間最長的患者超過了四年四個月。這些患者是劑量遞增研究中劑量最低的患者，但他們的情況非常好。

And the alpha-Gal continues to be produced at similar levels, which is very encouraging. There are so few patients out at that time that to do an eGFR slope would not be wise until more patients get to the longer time points.

而α-半乳糖繼續以相似的水平產生，這是非常令人鼓舞的。當時出門的患者很少，因此在更多患者到達較長時間點之前進行 eGFR 斜率測量並不明智。

Nathalie, anything?

娜塔莉，有什麼事嗎？

Yes. And I can also confirm that the positive eGFR slope that we are observing at this point is across all patients, whether they're started on ERT or they're naive or pseudo-naive, whether they're male or female.

是的。我還可以確認，我們此時觀察到的正 eGFR 斜率適用於所有患者，無論他們是開始接受 ERT 還是初次接受或假接受治療，無論他們是男性還是女性。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑弗里斯。

Congrats on the progress. As a follow-up to Gena's question earlier, I think you've mentioned you could include propensity match control data, too, as part of the filing package. Just wondering if you can comment on whether FDA will put more weight on comparing versus baseline or versus the propensity match control data.

祝賀取得的進展。作為 Gena 之前問題的後續，我認為您已經提到您也可以將傾向匹配控制資料包含在歸檔包中。只是想知道您是否可以評論 FDA 是否會更加重視與基線或傾向匹配控制數據的比較。

And can you talk about where you are at with getting the propensity match control data? Is that something that you think you will need in order to maximize potential with the partnership?

您能談談您在取得傾向配對控制資料方面的進展嗎？您認為為了最大限度地發揮合作潛力，您需要這樣做嗎？

So we can't comment -- we're unable to comment on how the agency will weigh the different pieces of data. What I can say is that throughout the discussions, they have said it's the totality of the data. So it's the eGFR, both compared as a group rather than individuals, compared as a group from baseline to one year and then two years compared to what's historically recognized for Fabry disease where there is over 5-point drop over the course of the year.

所以我們無法發表評論——我們無法評論該機構將如何權衡不同的數據。我能說的是，在整個討論過程中，他們都說這是數據的全部。因此，這是eGFR，既作為一個群體而不是個人進行比較，作為一個群體從基線到一年、然後兩年的比較，與歷史上公認的法布里病相比，法布里病在一年中下降了超過5 個百分點。

What's known about the ERT agents where there's between 1.5 and 2.5 reduction over the course of the year. But they'll also be looking at the sustained effect of alpha-Gal, the sustained control of lyso-Gb3, the alpha-Gal levels in the skin biopsies are significantly increased. They'll be looking at SF-36, the patient reports about pain, about FOS-MSSI. It's the whole body of this data set that is so compelling.

據了解，ERT 藥物在一年中減少了 1.5 到 2.5 倍。但他們也會關注 α-Gal 的持續作用、lyso-Gb3 的持續控制、皮膚活檢中的 α-Gal 水平顯著增加。他們將關注 SF-36，患者報告疼痛和 FOS-MSSI。正是這個數據集的整體才如此引人注目。

And everyone on ERT, I think this is just important to remind us, everyone, the 18 patients that came in on ERT have been taken off ERT and are very happily off ERT. So it's a really compelling data set of which the eGFR is like the thing that allows the agency to find us a way to approval, but is supported and made better by the totality of the data.

對於每個接受 ERT 的人，我認為這只是提醒我們，每個人，18 名接受 ERT 的患者已經停止了 ERT，並且非常高興地結束了 ERT。因此，這是一個非常引人注目的數據集，其中 eGFR 就像允許該機構為我們找到批准方法的東西，但得到了整體數據的支持並變得更好。

Got it. Yes, that all makes sense and it's helpful. And just wanted to clarify too for the milestone payment from Genentech for the $50 million. Did you receive all $50 million? Or was there $40 million recorded this quarter? And will you get an additional $10 million from the tech transfer? Just wanted to clarify on that.

知道了。是的，這一切都很有道理並且很有幫助。我也想澄清基因泰克公司里程碑式的 5000 萬美元付款。5000萬美元你都收到了嗎？還是本季記錄了 4000 萬美元？您會從技術轉移中獲得額外的 1000 萬美元嗎？只是想澄清這一點。

Maury, this is Prathyusha. Yes, we've received all of the $50 million. Only a portion of it, the $40 million was reflected in our quarter-end balance, which is what you're trying to bridge to.

莫里，這是普拉修莎。是的，我們已經收到全部 5000 萬美元。只有其中的一部分，即 4000 萬美元，反映在我們的季末餘額中，這正是您想要彌補的。

(Operator Instructions) Luca Issi, RBC Capital.

（操作員指令）Luca Issi，RBC Capital。

Obviously, congrats on the regulatory alignment. Maybe 2 quick questions here for me. On Fabry, at high level, can you just talk about how your conversation with the FDA has evolved over time? I find it fascinating that the FDA asked AVROBIO to run a head-to-head trial versus Fabrazyme using renal biopsies as the primary endpoint, not too long ago versus it sounds like the FDA is telling you that single arm looking at serum biomarker is now sufficient.

顯然，祝賀監管調整。也許有兩個問題想問我。關於 Fabry，您能談談您與 FDA 的對話隨著時間的推移是如何演變的嗎？我覺得很有趣的是，不久前 FDA 要求 AVROBIO 與 Fabrazyme 進行一項頭對頭試驗，以腎臟活檢作為主要終點，而聽起來 FDA 告訴你，單臂觀察血清生物標誌物現在是充足的。

So what has changed there in your view? Again, any color there would be much appreciated.

那麼您認為發生了什麼變化？同樣，任何顏色都會非常感激。

And then maybe on hemophilia A, maybe in the context of the BioMarin commercial debacle, if you will, how confident are you that Pfizer really will put a lot of energy and resources behind the approval and the commercial launch of this therapy?

然後，也許在血友病 A 方面，也許在 BioMarin 商業失敗的背景下，如果您願意的話，您對輝瑞真的會投入大量精力和資源支持該療法的批准和商業推出有多大信心？

Important questions. So I don't remember how long ago that AVROBIO had the discussion with the agency. Was it two, was it three, four years ago, where they were using preconditioning cell therapy to try and show the agency that there was a benefit to their medicine. And at that time, there were several companies, 4DMT, Freeline and others that were in the Fabry world. And then you fast forward and many of these have dropped out.

重要問題。所以我不記得AVROBIO多久前與該機構進行過討論。是兩年前，還是三、四年前，他們當時正在使用預處理細胞療法，試圖向該機構展示他們的藥物有好處。當時，Fabry 世界裡有幾家公司，4DMT、Freeline 等。然後你快進，其中許多都退出了。

And the other piece that's changed, I think, is Peter Marks' position at CBER, where he realizes that there is limitations on what can be required of small populations of genomic medicines for rare diseases and that he wants to help us, all of us, find a path forward for this. And so I think what Sangamo has agreed with the agency is simply the -- what Peter has been saying made into a plan for a very effective agent.

我認為，另一件事發生了變化，是 Peter Marks 在 CBER 的職位，他意識到針對罕見疾病的小群體基因組藥物的需求是有限的，他想幫助我們，我們所有人，為此找到一條前進的道路。因此，我認為桑加莫與該機構達成的協議是將彼得所說的內容納入一個非常有效的特工計劃中。

Nathalie, do you want to just walk through the timeline of how we got there?

娜塔莉，你想簡單介紹一下我們是如何到達那裡的嗎？

Yeah. So as you might recall, we had a Type C meeting earlier in 2024, where we agreed with the FDA to do a Phase 2b study with 25 patients for the basis of approval. Then after this, we had another data cut from our trial, STAR trial and realized that we had a positive eGFR slope in 18 patients that had more -- one year or more and also six patients at two years.

是的。您可能還記得，我們​​在 2024 年早些時候舉行了一次 C 型會議，會上我們同意 FDA 對 25 名患者進行 2b 期研究，作為批准的基礎。此後，我們從 STAR 試驗中獲得了另一項數據，並意識到我們在 18 名接受一年或以上的患者以及 6 名接受兩年的患者中發現了正的 eGFR 斜率。

At that time, we had scheduled a prime meeting with EMA. So this was our prime kickoff and in attendance with the FDA, in the spirit of global -- the FDA and EMA approach to have a global approach to approval for rare diseases. At that time, we presented to EMA the eGFR slope data and the FDA in attendance was very encouraged by this and asked us to submit the data to the FDA.

當時，我們安排了與 EMA 的重要會議。因此，這是我們的首要啟動，並本著全球精神——FDA 和 EMA 的精神，與 FDA 一起對罕見疾病進行全球審批。當時我們向EMA提交了eGFR斜率數據，與會的FDA對此非常鼓舞，要求我們將數據提交給FDA。

So because we have RMAT designation, we decided to do a Type B meeting where we describe our results to the FDA and ask if given this remarkable data of a positive eGFR slope in our 18 patients at one year, we could use eGFR slope as the primary basis of approval on an accelerated approval pathway in our Phase 1/2 study, alleviating the Phase 2b study that was originally planned. And the FDA agreed with our approach and that's where we are today.

因此，因為我們擁有 RMAT 資格，所以我們決定召開 B 類會議，向 FDA 描述我們的結果，並詢問我們是否可以使用 eGFR 斜率作為一年內 18 名患者的正 eGFR 斜率這一顯著數據。 /2 期研究中加速核准途徑的主要核准依據，減輕了原先計畫的2b 期研究的壓力。FDA 同意我們的方法，這就是我們今天的處境。

And I should say, in all my many years of working with the FDA, I've never seen a written response so clear. When asked if we could use the 12-month eGFR for accelerated approval, they said, yes, we agree. So we are very pleased with that. I think it hopefully is somewhat of a precedence for other rare diseases companies. They're trying to do their very best for patients that are in incredibly difficult circumstances.

我應該說，在我與 FDA 合作的這麼多年中，我從未見過如此明確的書面答覆。當被問及我們是否可以使用 12 個月的 eGFR 來加速審批時，他們說，是的，我們同意。所以我們對此非常滿意。我認為這有望成為其他罕見疾病公司的先例。他們正在盡力為處境極為困難的患者提供最好的幫助。

If I could switch to your second question, which was your reflections on the BioMarin launch of ROCTAVIAN. We are in a relationship with Pfizer. And so we're always very careful to reflect what Pfizer has told us. And before each conference call, we agree with them what it is, how they would like their medicine to be reflected. We're very pleased with the abstracts they're going to be showing at ASH.

我可以轉向你的第二個問題，即你對 BioMarin 推出 ROCTAVIAN 的看法。我們與輝瑞有合作關係。因此，我們總是非常小心地反映輝瑞告訴我們的內容。在每次電話會議之前，我們都會與他們達成一致，同意他們的藥物是什麼，以及他們希望如何反映他們的藥物。我們對他們將在 ASH 上展示的摘要感到非常滿意。

And I would encourage you to look at the data there and read from Pfizer's language about their enthusiasm for this product. But they have told us that we can say that they're in discussions with regulatory authorities. And that, to us, suggests Pfizer's continued enthusiasm for this product.

我鼓勵您查看那裡的數據並從輝瑞的語言中了解他們對該產品的熱情。但他們告訴我們，我們可以說他們正在與監管機構進行討論。對我們來說，這顯示輝瑞對該產品的持續熱情。

Ritu Baral, TD Cowen.

裡圖·巴拉爾，TD·考恩。

Sandy, since the FDA endpoint revolves around renal function, are they requiring or requesting any proportion or quantum of data from the pivotal data set be from female Fabry patients or patients with cardiac variant?

Sandy，由於 FDA 終點圍繞腎功能，他們是否需要或請求關鍵數據集中來自女性法布里患者或心臟變異患者的任何比例或數量的數據？

And if the answer is no, would you still be able to have some of that prospective data either in the open-label portion or from some other prospective analysis for a likely label at some point? Just as the cardiac variant and cardiac involvement of the disease gains importance, it might be an important commercial tool to have talking to the broader patient population.

如果答案是否定的，您是否仍然能夠在開放標籤部分或在某個時候從可能的標籤的其他前瞻性分析中獲得一些前瞻性數據？正如該疾病的心臟變異和心臟受累變得越來越重要一樣，它可能成為與更廣泛的患者群體進行交流的重要商業工具。

So the discussion with the agency has been that this is for Fabry. It hasn't been for men versus women or renal versus cardiac. It's been all Fabry patients, naive, pseudo-naive ERT, experienced men and women. Our discussions with them have largely been about eGFR because we have this remarkable data. And we will look at all the other pieces of the data set in the submission.

因此與該機構的討論是，這是給法布里的。這並不是男性與女性的對比，也不是腎臟與心臟的對比。都是法布里患者、天真的、偽天真的 ERT、經驗豐富的男人和女人。我們與他們的討論主要是關於 eGFR，因為我們擁有這些非凡的數據。我們將查看提交的資料集的所有其他部分。

I'll say again that when we measure alpha-Gal in the skin biopsies, it's increased. When we look at the renal function, it's increased -- or, sorry, it's improved. When we look at the patients' report of sweating, of how they feel of the FOS-MSSI, there is improvement across all of it. So one would expect that there's no reason why it wasn't having an effect on the heart as well as other parts of the body. And the 32-patient data set is all that the agency has asked for.

我要再說一遍，當我們在皮膚活檢中測量α-半乳糖時，它會增加。當我們觀察腎功能時，它有所增強——或者，抱歉，它有所改善。當我們查看患者的出汗報告以及他們對 FOS-MSSI 的感受時，我們發現所有這些都得到了改善。因此，人們會認為它沒有理由不對心臟和身體其他部位產生影響。該機構所要求的就是 32 名患者的資料集。

There will not be additional patients put in after that as part of the Sangamo clinical development program. Nathalie, however, the patients are very keen that this gets to them as soon as possible. Your team met with the Fabry support group recently. Do you want to talk a little of what they heard?

作為 Sangamo 臨床開發計劃的一部分，此後不會再招募更多患者。然而，納塔莉（Nathalie）的患者非常希望能夠盡快得到這些資訊。您的團隊最近與 Fabry 支援小組會面。你想談談他們聽到的一些事情嗎？

Yes. We were at the National Fabry Disease Foundation Patient Conference about three, four weeks ago and we held a patient group forum where we had patients that were on ERT, but we had also three patients that had received our gene therapy. And these patients are really very happy to have made that decision to enter the trial.

是的。大約三、四週前，我們參加了國家法布瑞氏症基金會患者會議，我們舉辦了一個患者小組論壇，其中有接受 ERT 的患者，但我們也有三名患者接受了我們的基因治療。這些患者真的非常高興做出了參加試驗的決定。

We have patients that report that they were working with cane. They now have dropped their cane. They're working normally. They feel so much better. Patient feel like it has a new lease on life.

我們有患者報告說他們正在使用拐杖工作。他們現在已經放下了手杖。他們工作正常。他們感覺好多了。患者感覺自己獲得了新生。

We have patients that have reduced pain. We have patients that now are taking job in the heat in the airport, carrying luggage and they're sweating and they feel great. So it's a general well-being that we're hearing from the patient. The patients that are on ERT are not very happy about their treatment.

我們有減輕疼痛的患者。我們的病人現在正在機場炎熱的天氣工作，提著行李，他們滿頭大汗，感覺很好。因此，我們從患者那裡聽到的是整體健康狀況。接受 ERT 的患者對他們的治療不太滿意。

First of all, it's very burdensome. Every two weeks you get a five to six hours infusion. Often, you have someone coming at home, you have to organize this. It's pretty invasive. And really, what we've heard from the patient is after 10 days of their ERT, they start feeling not well.

首先，這是非常沉重的負擔。每兩週您需要輸註五到六個小時。通常，您家裡有人來，您必須組織一下。這是相當具有侵略性的。事實上，我們從患者那裡聽到的是，在 ERT 10 天后，他們開始感到不舒服。

They're starting to have symptom coming back and they still have to wait. And they have other medications that they're taking around the ERT pre or post. So it's really not a very good treatment for the patient side. And because it's burdensome, we know that there is a large population of Fabry patients that do skip doses because of the burden of ERT treatment.

他們開始出現症狀，但仍然需要等待。他們在 ERT 前後也服用其他藥物。所以對於患者來說這確實不是一個很好的治療方法。而且由於 ERT 治療的負擔很重，我們知道有大量法布瑞氏症患者確實會因為 ERT 治療的負擔而跳過劑量。

Yes. We are very clear that ERT was a great advance in the treatment of Fabry. And we feel that this is now the next stage in that journey where they'll be able to get a single infusion of AV, extremely well tolerated with no serious adverse events related to the treatment and show this benefit over time. And it's a privilege to work on such a medicine and we look forward to finding the right partner to take this forward to get it to patients.

是的。我們非常清楚，ERT 是法布瑞治療的一大進步。我們認為，現在是這趟旅程的下一階段，他們將能夠獲得單次AV 輸注，耐受性極好，不會出現與治療相關的嚴重不良事件，並隨著時間的推移顯示出這種益處。能夠研究這種藥物是一種榮幸，我們期待找到合適的合作夥伴來推動這項藥物向患者提供。

The question-and-answer session is now closed. I'll now turn it back over to Louise Wilkie for closing remarks.

問答環節現已結束。現在我將把它轉迴路易絲·威爾基（Louise Wilkie）做總結發言。

Thank you and thank you once again for joining us today and for all of your questions. 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.

謝謝您，並再次感謝您今天加入我們並提出所有問題。請注意，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動態。謝謝。

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

感謝您參加今天的會議。這確實結束了該程式。您現在可以斷開連線。