Sangamo Therapeutics Inc (SGMO) 2024 Q4 法說會逐字稿

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

下午好，歡迎參加 Sangamo Therapeutics 2024 年第四季和全年電話會議。請注意，今天的會議正在錄音。

I would now like to turn the conference over to your speaker (technical difficulty) Please go ahead.

現在我想將會議交給您的發言人（技術困難）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 McCray, Chief Executive Officer; Nathalie Dubois-Stringfellow, Chief Development Officer; and Prathyusha Duraibabu, Chief Financial Officer.

謝謝。大家下午好。感謝您今天參加我們的電話會議。參加此電話會議的有 Sangamo 執行領導團隊的幾位成員，包括執行長 Sandy McCray； Nathalie Dubois-Stringfellow，首席開發長；和財務長 Prathyusha Duraibabu。

Slides from our corporate presentation can be found on our website, sangamo.com, and under the presentations page of the Investors and Media section.

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 related to Sangamo's cash runway, plans to obtain additional capital, and ability to continue operating as a going concern.

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、獲取額外資本的計劃以及繼續經營的能力相關的聲明。

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 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, regulatory approvals, upcoming catalysts and milestones, and other statements that are not historical fact.

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賺取和收到付款的能力、Sangamo 對新合作和許可協議的期望、Sangamo 及其合作者對臨床試驗、臨床數據展示和發布、監管提交、監管批准、即將到來的催化劑和里程碑的預期計劃和時間表以及其他非歷史事實的陳述。

Actual results may differ materially from what we discussed today. These statements are subject to certain risks and uncertainties that are discussed in our filings of the SEC, specifically in our annual report on Form 10-K, the fiscal year ended December 31, 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 10-K 表格年度報告、截至 2024 年 12 月 31 日的財政年度以及 Sangamo 不時向美國證券交易委員會提交的後續文件和報告中。

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。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。

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.

謝謝你，路易絲，祝今天參加電話會議的各位下午。

Sangamo's pipeline has made a great deal of progress since the start of 2024. We have advanced or prioritized neurology therapies towards the clinic, securing our first ever neurology IND in idiopathic small fiber neuropathy for chronic neuropathic pain and demonstrating non-clinical proof of concept for a product candidate in prime disease.

自 2024 年初以來，桑加莫的管道取得了巨大進展。我們已將神經病學療法推進或優先推向臨床，確保了我們首個針對慢性神經性疼痛特發性小纖維神經病變的神經病學 IND，並展示了針對主要疾病的產品候選物的非臨床概念驗證。

We showed that we are a collaborator of choice for neurotropic capsids with the announcement of two blue-chip pharma agreements for industry-leading delivery capsid STAC-BBB. The first with Genentech for Tau and a second neurology target, and the second with Astellas for up to five neurology disease targets.

我們宣布與兩家藍籌製藥公司簽署業界領先的遞送衣殼 STAC-BBB 協議，表明我們是神經營養衣殼的首選合作者。第一次合作是與 Genentech 合作，針對 Tau 和第二個神經病學目標，第二次合作是與 Astellas 合作，針對多達五種神經病學疾病目標。

We have a clear regulatory pathway to accelerated approval in Fabry disease which could reduce the time to potential approval by approximately three years. And our Fabry gene therapy study continues to generate best-in-class data with a pivotal data readout expected in mid-2025.

我們擁有明確的監管途徑來加速法布瑞氏症的審批，這可以將潛在審批時間縮短約三年。我們的法布里基因療法研究繼續產生一流的數據，預計在 2025 年中期獲得關鍵數據讀數。

From a financial standpoint since 2023, we have reduced our non-GAAP operating expenses by nearly half year over year. And in 2024 we raised over 100 million in funding through non-dilutive license fees and milestone payments as well as equity financing. And these are significant achievements for a company of our size.

從財務角度來看，自 2023 年以來，我們的非 GAAP 營運費用已年減了近一半。2024 年，我們透過非稀釋性授權費、里程碑付款以及股權融資籌集了超過 1 億美元的資金。對於我們這種規模的公司來說，這些都是重大成就。

Judged by all other metrics, this would have been a very successful year. However, we know, until we partner Fabry and appropriately capitalize the company for success, our work is not done. I want to re-emphasize that our number one priority continues to be addressing our financial needs. Sangamo must be well capitalized to fulfill our potential.

從其他所有指標來判斷，今年本該是非常成功的一年。然而，我們知道，除非我們與 Fabry 合作並適當地為公司的成功提供資金，否則我們的工作尚未完成。我想再次強調，我們的首要任務仍然是滿足我們的財務需求。Sangamo 必須擁有充足的資本才能發揮我們的潛力。

We continue to engage in Fabry business development negotiations, and securing a commercial partner is our key focus. Interest in this program has been strong. This is proving to be a time-consuming process, as discussions of this nature are complex and facilitating the extensive due diligence required by potential partners takes time.

我們繼續參與 Fabry 業務發展談判，確保商業合作夥伴是我們的重點。人們對該計劃的興趣一直很濃厚。事實證明這是一個耗時的過程，因為這種性質的討論很複雜，而且促進潛在合作夥伴所需的廣泛盡職調查需要時間。

We remain committed to securing an anticipated partnership in the second quarter of 2025 that is best suited to bringing ST-920 to Fabry patients upon potential approval and that provides capital for Sangamo to execute on its other programs. We will share information as soon as we're able. Furthermore, we're actively engaged in advanced contract negotiations with a potential collaborator for third STAC-BBB license agreement and are hopeful of having more news to share near the end of this quarter.

我們仍然致力於在 2025 年第二季度達成預期的合作夥伴關係，以便在獲得批准後將 ST-920 帶給法布里病患者，並為 Sangamo 執行其他項目提供資金。我們將盡快分享資訊。此外，我們正在積極與潛在合作者就第三個 STAC-BBB 許可協議進行高級合約談判，並希望在本季度末有更多消息可以分享。

I would now like to hand it over to Nathalie, our Head of Development, who will walk us through detailed pipeline developments. Nathalie.

現在，我想把它交給我們的開發主管 Nathalie，她將向我們介紹詳細的管道開發。娜塔莉。

Thank you, Sandy. First, I'd like to provide updates on ST-503, our investigational epigenetic regulator for the treatment of chronic neuropathic pain, which is ready to enter the clinic. Our initial indication is an idiopathic small fiber neuropathy, or iSFN, a peripheral neuropathy that results in highly debilitating symptoms such as burning, prickling, stabbing, or lightning-like pain. That is estimated to impact about 43,000 people in the United States. More broadly, peripheral neuropathy are estimated to affect nearly 40 million Americans.

謝謝你，桑迪。首先，我想介紹 ST-503 的最新情況，ST-503 是我們正在研究的用於治療慢性神經性疼痛的表觀遺傳調節劑，已準備好進入臨床。我們最初的適應症是特發性小纖維神經病變（iSFN），這是一種導致嚴重衰弱症狀的周邊神經病變，例如灼熱感、刺痛感、刺痛感或閃電狀疼痛。據估計，這將影響美國約 43,000 人。更廣泛地說，估計週邊神經病變影響著近 4000 萬美國人。

As we've shared previously, a significant body of evidence implicates sodium channels in mediating the pathophysiology of neuropathic pain. ST-503 is a zinc finger repressor, or ZFR, targeting the human gene SCN9A that encodes the Nav1.7 sodium channel. Developing small molecules that specifically target Nav1.7 is challenging due to the high-structural similarities between different sodium channels, making it difficult to achieve selectivity and avoid off-target effects. We believe our epigenetic regulation approach is differentiated.

正如我們之前所分享的，大量的證據表明鈉通道介導神經性疼痛的病理生理學。ST-503 是一種鋅指阻遏物（ZFR），針對編碼 Nav1.7 鈉通道的人類基因 SCN9A。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，難以實現選擇性並避免脫靶效應。我們相信我們的表觀遺傳調控方法是與眾不同的。

By directly targeting the SCN9A gene, ST-503 are shown to precisely and potentially reduce the expression of Nav1.7 sodium channel in sensory neurons in animal models and significantly reduce pain hypersensitivity following a single intrathecal administration. ST-503 has been well tolerated in non-human primates with no off-target effect observed. Following FDA clearance of the IND in November 2024, our first ever neurology IND, we are actively preparing for a Phase 1/2 study to assess the safety, durability, and preliminary efficacy of a one-time dose of ST-503 administered intrathecally to patients with intractable pain due to iSFN.

透過直接針對 SCN9A 基因，ST-503 已被證明能夠精確且潛在地降低動物模型中感覺神經元中 Nav1.7 鈉通道的表達，並在單次鞘內給藥後顯著降低疼痛過敏症。ST-503 在非人類靈長類動物中耐受性良好，未觀察到脫靶效應。繼 2024 年 11 月 FDA 批准我們的首個神經病學 IND 之後，我們正在積極準備進行 1/2 期研究，以評估對因 iSFN 引起頑固性疼痛的患者鞘內注射一次性劑量 ST-503 的安全性、持久性和初步療效。

This multi-center, double-blind, randomized, sham-controlled dose escalation study is designed to evaluate three ascending doses beginning with what we believe to be the minimally efficacious dose as determined from animal studies. Patients will be randomized in a two to one ratio to receive either ST-503 or a sham treatment with three patients planned in each of the first two dose cohorts, and up to nine patients in the top-dose cohort.

這項多中心、雙盲、隨機、假對照劑量遞增研究旨在評估三種遞增劑量，從我們認為的動物研究確定的最低有效劑量開始。患者將以二比一的比例隨機分配接受 ST-503 或假治療，前兩個劑量組各計畫接受三名患者，最高劑量組最多接受九名患者。

The primary objectives of this Phase 1/2 study will be to assess the safety and tolerability of ST-503 with secondary objectives to assess preliminary efficacy based on the impact of ST-503 on refractory pain and assessment of the multi-dimensional impact of ST-503 on sleep, mental health, and quality of life.

這項 1/2 期研究的主要目標是評估 ST-503 的安全性和耐受性，次要目標是根據 ST-503 對難治性疼痛的影響評估初步療效，並評估 ST-503 對睡眠、心理健康和生活品質的多維影響。

We strongly believe in the potential of ST-503 to reversionalize the chronic pain landscape. And if successful, significant opportunity exists to broaden its application to patient populations suffering from other types of chronic neuropathic pain. We plan to begin patient enrollment and dosing in mid-2025 and anticipate having preliminary proof-of-efficacy data in the fourth quarter of 2026.

我們堅信 ST-503 具有扭轉慢性疼痛狀況的潛力。如果成功的話，將有很大機會將其應用範圍擴大到患有其他類型慢性神經性疼痛的患者群體。我們計劃於 2025 年中期開始患者招募和給藥，並預計於 2026 年第四季獲得初步療效證明數據。

Moving to our Prion Disease program, we continue to advance clinical trial authorization, or CTA, enabling activities and expect a CTA submission in the UK in the first quarter of 2026. As a reminder, this program leverages our novel STAC-BBB capsid which, if safe and effective, could validate our broader neurology pipeline.

轉向我們的朊病毒疾病項目，我們繼續推進臨床試驗授權（CTA）支持活動，並預計在 2026 年第一季在英國提交 CTA。提醒一下，該計劃利用了我們新穎的 STAC-BBB 衣殼，如果其安全有效，則可以驗證我們更廣泛的神經學管道。

Prion disease is a rapidly fatal and incurable neurogenerative disease caused by the misfolding of the prion protein encoded by the PRNP gene. At least 1,300 new cases of prion disease are identified each year in the United States and in Europe with a similar presence globally.

朊病毒病是一種迅速致命且無法治癒的神經退化性疾病，由 PRNP 基因編碼的朊病毒蛋白錯誤折疊引起。美國和歐洲每年至少發現 1,300 例新的朊病毒病病例，全球的病例數也類似。

This quarter we published a manuscript in bioRxiv demonstrating non-clinical proof of concept for our epigenetic regulation approach. A single intravenous infusion of our ZFR significantly reduced expression of prion mRNA and protein in the mouse brain, extended mouse survival, and improved an array of molecular, histological biomarker and behavior readouts even when administered post symptomatically to mice with prion disease.

本季度，我們在 bioRxiv 上發表了一篇手稿，展示了我們的表觀遺傳調控方法的非臨床概念驗證。單次靜脈輸注我們的 ZFR 可顯著降低小鼠腦中朊病毒 mRNA 和蛋白質的表達，延長小鼠的存活時間，並且改善一系列分子、組織學生物標記和行為讀數，即使在對患有朊病毒疾病的小鼠出現症狀後再進行注射也是如此。

In addition, a single, intravenous administration of the prion ZFR delivered via STAC-BBB to non-human primates resulted in potent and widespread reduction of prion expression in transduced neurons throughout the brain. This is a significant result in a highly challenging disease with no treatment options today. We plan to begin clinical trial enrollment and dosing in mid-2026 and expect to have preliminary clinical data in prion disease in the fourth quarter of 2026.

此外，透過 STAC-BBB 向非人靈長類動物單次靜脈注射朊病毒 ZFR，可導致整個大腦中傳導神經元的朊病毒表達強效且廣泛地減少。對於這種目前尚無治療方法的極具挑戰性的疾病來說，這是一個重要的結果。我們計劃於 2026 年中期開始臨床試驗招募和給藥，並預計在 2026 年第四季獲得朊病毒病的初步臨床數據。

Moving now to Fabry, at the World Symposium in February, we presented impressive updated preliminary clinical data from our Phase 1/2 STAAR study of isaralgagene civaparvovec, or ST-920, our investigational gene therapy for the treatment of Fabry disease. This latest data, which shows significant sustained benefit, improvement in kidney function, and a favorable safety profile, continue to demonstrate the potential of ST-920 as a one-time durable treatment option for Fabry disease that can improve patient outcomes.

現在談談法布瑞氏症，在二月的世界研討會上，我們展示了 isaralgagene civaparvovec（或 ST-920）的 1/2 期 STAAR 研究的令人印象深刻的最新初步臨床數據，該研究是我們用於治療法布瑞氏症的基因療法。最新數據顯示，ST-920 具有顯著的持續益處、腎功能的改善和良好的安全性，繼續證明了 ST-920 作為法布瑞氏症一次性持久治療選擇的潛力，可以改善患者的預後。

In the 33 patients treated with ST-920, elevated expression of alpha-Gal A activity was maintained for nearly four years for the longest treated patients. Importantly, we observe a positive mean eGFR slope of 3.061 mL of cleans blood per minute per body surface in the 23 patients with at least one year of follow-up, indicating notable improvement in renal function.

在接受 ST-920 治療的 33 名患者中，治療時間最長的患者的 alpha-Gal A 活性表達升高維持了近四年。重要的是，我們觀察到在至少追蹤一年的 23 名患者中，每分鐘每體表清潔血液的平均 eGFR 斜率為正 3.061 毫升，顯示腎功能顯著改善。

For context, the average untreated patient in Fabry disease as an eGFR slope of minus three or minus four, to this statistically significant positive eGFR slope is a remarkable achievement. All 18 patients who begin the study on enzyme replacement therapy, or ERT, have been successfully withdrawn from ERT and remain off ERT.

就背景而言，未經治療的法布瑞氏症患者的平均 eGFR 斜率為負三或負四，而這一具有統計意義的正 eGFR 斜率是一個了不起的成就。開始接受酵素替代療法 (ERT) 研究的所有 18 名患者均已成功退出 ERT 並繼續停止接受 ERT。

We also observed notable improvement in quality of life among the patient with at least one-year follow-up. For example, among the shortform-36 quality-of-life score, we saw a mean change in the general health score of 10.6, as well as significant improvement in physical component, bodily gain, physical vitality, social function, and emotional well-being scores.

我們也觀察到，經過至少一年的隨訪，患者的生活品質有了顯著改善。例如，在短表36項生活品質評分中，我們看到整體健康評分平均變化了10.6，且身體組成、身體增益、身體活力、社會功能和情緒健康評分都有顯著改善。

The FTS provides us with a clear regulatory pathway to accelerate approval for ST-920 using eGFR slope at 52 weeks across all patients as an intermediate clinical endpoint. The 52-weeks eGFR slope data from all enrolled patients in the Phase 1/2 STAAR study will be available in the first half 2025.

FTS 為我們提供了一條清晰的監管途徑，以所有患者 52 週的 eGFR 斜率作為中期臨床終點，加速 ST-920 的批准。所有參與 1/2 期 STAAR 研究的患者的 52 週 eGFR 斜率數據將於 2025 年上半年提供。

We are thrilled with how the data are progressing and look forward to providing future updates as the full 52-weeks data become available in the middle of this year. We're actively preparing all necessary activity for the BLA, including manufacturing readiness, and continue to work towards a potential BLA submission in the second half of 2025. We're excited that this potential medicine could be commercialized as early as the second half of 2026, which would be an incredible achievement for Fabry patients need.

我們對數據的進展感到非常興奮，並期待在今年年中完整 52 週數據發布後提供未來的更新。我們正在積極準備 BLA 的所有必要活動，包括製造準備，並繼續努力在 2025 年下半年提交 BLA。我們很高興這種潛在的藥物最早可以在 2026 年下半年實現商業化，這對法布瑞氏症患者來說將是一項了不起的成就。

I will now hand it back to Sandy for closing remarks.

現在我將把發言權交還給桑迪，請她作最後發言。

Thank you, Nathalie. In closing, we're pleased with the progress we've made this year as we transition to becoming a clinical stage neurology company.

謝謝你，娜塔莉。最後，我們對今年向臨床階段神經病學公司轉型所取得的進展感到非常高興。

We have advanced our long-planned neurology pipeline towards the clinic, securing our first ever neurology IND and with patient dosing expecting in the coming months. We have shown Sangamo to be the collaborator of choice for neurotrophic capsids with the announcement of two blue-chip pharma agreements for STAC=BBB.

我們已將長期規劃的神經病學研發管線推進至臨床階段，並獲得了首個神經病學 IND，預計將在未來幾個月內為患者提供藥物。隨著我們宣布與 STAC=BBB 簽署兩項藍籌製藥協議，我們已證明 Sangamo 是神經營養衣殼的首選合作者。

And we have secured a clear regulatory pathway to accelerated approval in Fabry disease which would reduce the time to potential approval by approximately three years. We are proud of this progress and excited to be so close to the anticipated dosing of patients in our first-ever neurology clinical trial.

我們已經確保了法布瑞氏症加速審批的明確監管途徑，這將使潛在審批時間縮短約三年。我們為這項進展感到自豪，並很高興我們首次神經病學臨床試驗的患者劑量如此接近預期。

In parallel, we remain resolutely focused on raising the additional capital needed to set Sangamo up for its success. As I outlined earlier, we're in the very late-stage business development negotiations for a third potential STAC-BBB license agreement.

同時，我們仍堅定地致力於籌集 Sangamo 取得成功所需的額外資金。正如我之前概述的，我們正處於第三個潛在 STAC-BBB 授權協議的後期業務發展談判中。

We have compelling Fabry data with a pivotal data readout expected in the coming months. And business development negotiations for a potential Fabry commercialization agreement continue to advance with several interested partners. We believe we can solve both our short-term and long-term financing needs and look forward to providing additional updates as soon as they become available.

我們擁有令人信服的法布瑞氏症數據，預計未來幾個月將獲得關鍵數據讀數。並且，與幾家有興趣的合作夥伴就潛在的 Fabry 商業化協議進行的業務發展談判仍在繼續推進。我們相信我們可以解決我們的短期和長期融資需求，並期待在獲得更多更新後立即提供。

Operator, please open the line for questions.

接線員，請打開熱線來回答問題。

(Operator Instructions)

（操作員指示）

Luis Santos, H.C. Wainwright.

路易斯桑托斯，H.C.溫賴特。

Hello, everyone. Thank you so much for taking our questions. This is Luis for Patrick Trucchio. I was wondering if you're still waiting on any data for the Fabry program, and as you expect this partnership next discussions to be -- to lead to results next quarter.

大家好。非常感謝您回答我們的問題。我是路易斯，代表帕特里克·特魯基奧 (Patrick Trucchio) 發言。我想知道您是否仍在等待 Fabry 計劃的任何數據，並且正如您所期望的那樣，接下來的合作關係討論將在下個季度產生結果。

Similar question for the [eurovac] in, MA. Should we be expecting any more data later this year and would that facilitate any partnerships there? Thank you.

馬薩諸塞州的 [eurovac] 也有類似的問題。我們是否應該期待今年稍後獲得更多數據？這是否會促進合作？謝謝。

Thank you, Luis. So the Fabry partnership, we would love to have announced it. We would -- we're in late-phase discussions across several partners, potential partners, and look forward to taking that forward and finding the right place for the right -- for the patients and for the right partnership for our shareholders.

謝謝你，路易斯。因此，我們很高興宣布與 Fabry 的合作。我們正在與多個合作夥伴和潛在合作夥伴進行後期討論，並期待推動這一進程，為患者和股東找到合適的合作夥伴。

These things take time. The route forward from the agency was as recently as the end of October. We've had to compress the planning for the file and launch from what was 3, 3.5 years down to 6 months to the filing and then to the launch. And so there's a huge amount of activities that are going on.

這些事情需要時間。該機構最近於 10 月底發布了這項進展。我們必須將文件提交和發布的規劃時間從 3 到 3.5 年壓縮到 6 個月，再到發布。因此，有大量的活動正在進行中。

What I can reassure you is the data that Nathalie and her team showed in at the World Symposium remains positive, remains very positive, and we look forward to seeing the one-year data for the last patient as soon as next month, and that will allow us to drive this forward. Now it's a matter of closing the deal and making sure we find the right partner.

我可以向你們保證的是，娜塔莉和她的團隊在世界研討會上展示的數據仍然是積極的，仍然非常積極，我們期待最早在下個月看到最後一位患者的一年數據，這將使我們能夠推動這一進程。現在的問題是完成交易並確保我們找到合適的合作夥伴。

For the hemophilia, that was returned to us or the termination notice was given over the holiday period. And the more we see from Pfizer, the more we realize that it really was days away from both US and a European filing.

對於血友病，該合約已退還給我們，或在假期期間發出了終止通知。我們從輝瑞公司了解到的資訊越多，我們就越意識到，它距離向美國和歐洲提交申請真的只有幾天的時間了。

Our team are sitting closely with the Pfizer organization to understand and explore all possibilities for a transition. Ideally, we would like to hand this directly to a partner without having to go through Sangamo, but these are very early days to be able to give you a commitment to that plan. What I can tell you is that we've already had incoming interest on the hemophilia program. But I don't want to overpromise until we have a chance to understand all the data and speak with potential partners.

我們的團隊正與輝瑞公司密切合作，了解並探索過渡的所有可能性。理想情況下，我們希望直接將其交給合作夥伴，而不必通過 Sangamo，但現在還為時過早，無法向您承諾該計劃。我可以告訴你的是，我們已經對血友病計畫產生了興趣。但在我們有機會了解所有數據並與潛在合作夥伴交談之前，我不想過度承諾。

Just to clarify, are you -- do you get the rights to all of the data? Will you have access to all of that and you will be able to share at some point?

只是為了澄清一下，您是否擁有所有數據的權利？您是否可以存取所有這些內容並且能夠在某個時候分享？

We will have access to all the data from Pfizer. It's very clearly laid out in the contract, but that's a huge amount of data for something that was about to be filed in but a few days' time. And like you, we respect the idea that if someone goes into a clinical trial, you have a responsibility to make the data available.

我們將可以存取輝瑞的所有數據。合約中對此有非常明確的規定，但對於幾天後就要提交的文件來說，這數據量太大了。和您一樣，我們尊重這樣的想法：如果有人參加臨床試驗，您有責任提供數據。

Thank you so much.

太感謝了。

Yanan Zhu, Wells Fargo.

朱亞南，富國銀行。

Hi, thanks for taking our questions. This is [Kwan Ang] for Yanan. So, our question is also around Fabry. So can you share, have the interesting party I've seen any data beyond the World Symposium data. I think that data has a data card in, I think, September of 2024. So any updated data partners, potential partner have seen beyond that. Thank you.

您好，感謝您回答我們的問題。這是延安的[Kwan Ang]。所以，我們的問題也與法布瑞氏症有關。那麼，您能否分享我所見過的除世界研討會數據之外的任何有趣的數據。我認為該數據在 2024 年 9 月有數據卡。因此，任何更新的數據合作夥伴、潛在合作夥伴都已經看到了這一點。謝謝。

I'm looking to Nathalie here and who's shaking her head. We believe they haven't seen any efficacy data beyond what we've seen.

我看著娜塔莉，她正搖頭。我們相信他們沒有看到任何超出我們所見的功效數據。

Yes.

是的。

They have seen lots of other data. They've seen data about the manufacturing, about the CMC process. They've seen broader versions of the data cut that you saw, but they haven't seen later data. We now have seen data for up to 30 patients, and there's only 2 more patients to complete their journey before we have the complete data set and can pull that together for the file.

他們已經看到了許多其他數據。他們已經看到了有關製造和 CMC 工藝的數據。他們看到了您所看到的資料片段的更廣泛的版本，但他們還沒有看到後來的資料。現在我們已經看到了多達 30 名患者的數據，只需再有 2 名患者完成他們的治療過程，我們就能獲得完整的數據集並將其匯總到文件中。

Got it. That's super helpful. And for the 30-patient data you have seen so far, is the eGFR data consistent with what you have presented at work?

知道了。這非常有幫助。而對於您目前看到的 30 名患者的數據，eGFR 數據是否與您在工作中呈現的數據一致？

You can understand that I can't give you more details, but we remain very encouraged by the data set and look forward to following it because we feel that it's fulfilling all that the agency is asking for.

您可以理解我無法為您提供更多細節，但我們仍然對資料集感到非常鼓舞，並期待著關注它，因為我們認為它滿足了該機構的所有要求。

Yeah, super helpful. Thank you so much.

是的，非常有幫助。太感謝了。

Maury Raycroft, Jefferies.

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

Hi, thanks for taking my question. I was going to ask on the STAC-BBB deal just clarifying on that you said you could have that in place by the end of this month, is that correct? And then is there more you can say on what the upfront for that one could look like?

你好，謝謝你回答我的問題。我本來想詢問 STAC-BBB 協議，只是想澄清一下，您說可以在本月底完成該協議，對嗎？那麼，您能再多說一下這個預付款的具體情況嗎？

So I think you could look at what we've got as upfronts for the previous two deals. There's no almost like a standard market price for those.

所以我認為你可以看看我們在前兩筆交易中得到的預付款。對於這些產品來說，幾乎沒有一個標準的市場價格。

Yeah, we're guiding at the end of the year. We hope the end of the quarter -- thank you, Louise. We had hoped to have done it in time for this quarterly call and just these things are not always in our hands. But we know that the partner is one that you will find a very logical blue-chip choice, and we feel that we are putting a capsid in the hands of another great company that will allow their neurology pipeline and ours, frankly, to advance.

是的，我們將在年底進行指導。我們希望本季結束——謝謝你，路易絲。我們原本希望能在本次季度電話會議之前完成這項工作，但這些事情並不總是在我們掌控之中。但我們知道，合作夥伴是一個非常合理的藍籌選擇，我們覺得我們正在把一個衣殼放在另一家偉大的公司手中，這將使他們的神經病學管道和我們的神經病學管道坦率地向前發展。

Got it. That's helpful. And just a quick question on OpEx. Just how you're thinking about that going forward and once you solidify the partnership for Fabry, how that could change.

知道了。這很有幫助。關於 OpEx 的一個簡單問題。您如何看待未來的發展？一旦您鞏固了與 Fabry 的合作關係，情況將會發生怎樣的變化？

Hi, Maury, how are you? From the OpEx itself, we've done everything proactively what's in our control. We've reduced our OpEx by nearly half over year over year, and we've designed our OpEx for '25 to be very focused on taking our neurology pipeline forward. So from a guidance perspective, we've guided to keeping the same level of OpEx as last year as we move both Nav1.7 and pre-on forward.

嗨，莫里，你好嗎？從營運支出本身來看，我們已經積極主動地做了一切能控制的事情。與去年同期相比，我們的營運支出減少了近一半，並且我們設計的 25 年營運支出將非常注重推動我們的神經病學管道向前發展。因此，從指導角度來看，在推進 Nav1.7 和 pre-on 的過程中，我們指導維持與去年相同的營運支出水準。

Understood. Okay, thanks for taking my questions.

明白了。好的，感謝您回答我的問題。

(Operator Instructions)

（操作員指示）

Nicole Germino, Truist.

妮可·傑米諾（Nicole Germino），Truist。

Good afternoon and thanks for taking my question. So there's some literature around hypotension associated with inhibition of Nav.1 channel, sodium channels. So I have two questions. Do you have any hypotheses on how and why you're not seeing any hypotension so far on animal models. Or rather maybe how do you get investors comfortable around any potential hypotension concerns? And then second question, can you help us understand the patient-enrollment criteria for patients enrolling into the Nav1.7 study?

下午好，感謝您回答我的問題。有一些文獻報告了與 Nav.1 通道、鈉通道抑制有關的低血壓。我有兩個問題。您是否有任何假設，說明為什麼到目前為止在動物模型上沒有看到任何低血壓？或者更確切地說，您如何讓投資人放心面對潛在的低血壓問題？第二個問題，您能幫助我們了解參加 Nav1.7 研究的病患入選標準嗎？

Natalie, can you talk to these?

娜塔莉，你能談談這些嗎？

Yes. So we have not seen any effect on hypotension in all our animal studies, especially in the NHP study where it's a GLP study where we monitor the function very closely.

是的。因此，我們在所有動物研究中均未看到對低血壓的任何影響，特別是在 NHP 研究中，這是一項 GLP 研究，我們非常密切地監測其功能。

I think the Nav1.7 relationship with hyper or hypotension is not really well established. I think there is one report on a small molecule that was reported and the protein was -- the small molecule was delivered IV to the channel, and we don't know the specificity. We don't have that information. So I think it's too early to make the conclusion that Nav1.7 -- or there's not enough evidence to show that Nav1.7 could impact hyper or hypotension.

我認為 Nav1.7 與高血壓或低血壓的關係尚未得到很好的證實。我認為有一份關於小分子的報告，其中的蛋白質—小分子透過靜脈注射輸送到通道，我們不知道其特異性。我們沒有這些資訊。因此我認為現在就得出 Nav1.7 的結論還為時過早——或者沒有足夠的證據表明 Nav1.7 會影響高血壓或低血壓。

And all the monkeys are closely monitored. The blood pressure is monitored and they've all done very well, so we feel it's a very different situation.

所有的猴子都受到嚴密監控。血壓受到監測，而且他們的表現都很好，所以我們覺得這是一個非常不同的情況。

And then it's also intrathecal as well.

而且它也是鞘內的。

It's intrathecal, yes.

是的，它是鞘內的。

And there was a second question.

還有第二個問題。

On the patient enrollment criteria. So we're targeting patients with iSFN, as mentioned, and there is a bunch of inclusion-exclusion criteria that will be you know highlighted when we publish at clinicaltrials.gov design in design and [publictrial].gov. So is there anything specific you're looking for?

關於患者入選標準。因此，正如所提到的，我們針對的是患有 iSFN 的患者，並且有一系列納入排除標準，當我們在 clinicaltrials.gov 設計中和 [publictrial].gov 上發佈時，這些標準將會被重點強調。那麼，您正在尋找什麼具體的東西嗎？

Just overall the patient description for the iSFN-patient population, if there's anything that -- if there's anything of note.

總體而言，對於 iSFN 患者群體的患者描述，如果有任何值得注意的地方。

I don't think so. We're -- there's always a balance between having as pure a population and trying to avoid comorbidities, and that's always a fine needle to a fine path to try and execute, but I think the team have done a nice job of getting a recruitable study that will give us a clear answer. And we, I think, it's important to emphasize that this is a one-time treatment and, therefore, the benefit risk is really important. And therefore a clear result is what we need to look for for the powerful effect that we believe if the animal models are replicated that this molecule should achieve.

我不這麼認為。我們 — — 在擁有純粹的人群和盡量避免合併症之間總是存在著一種平衡，而這總是一條需要嘗試和執行的精細路徑，但我認為團隊已經很好地完成了一項可招募的研究，這將給我們一個明確的答案。我認為，我們必須強調，這是一種一次性治療，因此，效益風險非常重要。因此，我們需要尋找一個明確的結果，以證明我們相信如果複製動物模型，這種分子就會達到強大的效果。

Great thank you so much.

太好了，非常感謝。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

Thank you. I have two sets of questions. First one is regarding the Fabry deals. Just wanted to know that the delay on Fabry deal that potentially to you, was that due to the deal-term agreement, or is that because the potential partner wanted to see additional data or regulatory certainties. And then are you still looking for deal term to cover the, I think, almost two years OpEx until you reach, like say, 4Q '26 be able to show the proof concept data from both internal program.

謝謝。我有兩組問題。第一個是關於 Fabry 交易的。我只是想知道，對您來說，Fabry 交易的延遲可能是由於交易條款協議，還是因為潛在合作夥伴希望看到更多數據或監管確定性。然後，您是否仍在尋找交易期限來涵蓋幾乎兩年的營運支出，直到您到達比如說 26 年第四季度，能夠展示來自兩個內部程序的證明概念數據。

And the second question is regarding the 503. For Q '26 data update, do you expect to identify going forward those and what is your goal of a placebo adjusted pain score reduction?

第二個問題是關於 503 的。對於 Q'26 數據更新，您是否希望在未來確定這些內容以及安慰劑調整疼痛評分減少的目標是什麼？

So Gena, thank you for your questions. The Fabry discussions are going well. The clinical results are so compelling that each of the partners is fascinated by it. We can't discuss the terms and we can't discuss what we're in negotiation over. I'm sure you understand that. But the overall goal of Sangamo has to be to get us well-funded to get to that point at the end of next year where we can demonstrate the effect of Nav1.7 and hopefully show early results for prion disease.

所以，吉娜，謝謝你的提問。法布瑞氏症的討論進展順利。臨床結果非常引人注目，以至於每個合夥人都為之著迷。我們不能討論條款，也不能討論我們正在談判的內容。我相信你明白這一點。但 Sangamo 的總體目標是讓我們獲得充足的資金，以便在明年年底實現這一目標，屆時我們可以展示 Nav1.7 的效果，並希望展示朊病毒疾病的早期結果。

So that's our overall mission and as we get closer and closer to the pre-BLA meeting in the summer and the file by the end of the year, you can imagine that the energy around the discussions increases. Nathalie, you had a question as well, didn't you?

這就是我們的整體使命，隨著我們越來越接近夏季的 BLA 前會議和年底的文件，你可以想像討論的能量會增加。娜塔莉，你也有一個問題，不是嗎？

Yeah, yes, on the ST-503. So to be successful, a product candidate needs to demonstrate both near-term efficacy and long-term effect. In our trial, we hope to see a reduction in pain within the first 12 weeks. We understand the placebo effect, which is an important consideration, and as we've planned for our Phase 1/2 study design.

是的，是的，在 ST-503 上。因此，為了獲得成功，候選產品需要展現近期功效和長期效果。在我們的試驗中，我們希望在前 12 週內看到疼痛減輕。我們了解安慰劑效應，這是一個重要的考慮因素，正如我們為第 1/2 階段研究設計所計劃的那樣。

But you have to consider also that it's a one-time therapy. So our approach is very different to traditional therapy where the placebo control has been documented where then the sham treatment are taken regularly, which really can straighten the reminder of the placebo effect. So just as a reminder, this is a one-time potential treatment with one injection, and we believe the placebo effect will start to wane as we get further away from the point of administration.

但你還必須考慮到這只是一次性治療。因此，我們的方法與傳統療法非常不同，傳統療法已記錄了安慰劑對照，然後定期進行假治療，這確實可以糾正安慰劑效應的提醒。因此需要提醒的是，這是一種一次性注射的潛在治療方法，我們相信，隨著距離注射時間越來越遠，安慰劑效應將開始減弱。

And as I mentioned, we think looking at the data in from the animal study that really, we should have a near-term efficacy fairly quickly. In our animal study, I would say that the effect is maximal and plateau at about three to four weeks after administration.

正如我所提到的，我們認為，根據動物研究的數據，我們應該很快就能得到近期療效。在我們的動物研究中，我認為效果在給藥後約三至四周達到最大並穩定。

Are you looking for any placebo or just the pain-score reduction, you would be looking for like a two score or any particular scores you have in mind, giving some benchmark.

您是在尋找安慰劑還是只是尋找疼痛評分的減少，您會尋找兩個分數或您想到的任何特定分數，以提供一些基準。

We wouldn't be wise to set ourselves a target of the amount of reduction. This is clinical signs, and the first time it's been administered in humans. We hope that it will be a significant effect because this is a dreadful disease and intractable pain is not something anyone would wish to have. And we look forward to sharing the results with you over the coming year to 18 months.

為自己設定減排量的目標是不明智的。這是臨床症狀，也是首次在人體使用。我們希望它會產生顯著的效果，因為這是一種可怕的疾病，頑固性疼痛是任何人都不願意經歷的。我們期待在未來一年到一年半內與您分享成果。

Thank you.

謝謝。

Thank you. I am showing no further questions. I would now like to turn the call back to Louise Wilkie for closing remarks. Madam.

謝謝。我沒有其他問題。現在我想請路易斯‧威爾基 (Louise Wilkie) 致閉幕詞。女士。

Thank you and thanks once again for joining us today on the call and for 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.

謝謝您，再次感謝您今天參加我們的電話會議並提出您的問題。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。

This concludes today's conference call. Thank you for participating. You may now disconnect.

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。