RICHMOND, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced updated preliminary data from the Phase 1/2 STAAR clinical study evaluating isaralgagene civaparvovec, or ST-920, a wholly owned gene therapy product candidate for the treatment of Fabry disease.

加利福尼亚州里士满（商业新闻短讯）--基因组医学公司Sangamo Therapeutics，Inc.（纳斯达克：SGMO）今天宣布了1/2期STAAR临床研究的最新初步数据，该研究评估了ISARAGAGENE civaparvovec或ST-920，这是一种全资拥有的用于治疗法布里病的候选基因治疗产品。

In the largest known clinical gene therapy program in Fabry disease to date, data from 24 patients continued to show durable safety and preliminary efficacy data as of the data cutoff date, which continue to underscore the potential of isaralgagene civaparvovec as a single-dose treatment option for Fabry disease..

在迄今为止已知的最大的法布里病临床基因治疗计划中，截至数据截止日期，来自24名患者的数据继续显示出持久的安全性和初步疗效数据，这继续强调了isaralgagene civaparvovec作为法布里病单剂量治疗选择的潜力。。

These data will be shared at the 20th Annual WORLDSymposiumTM in San Diego, CA on Wednesday, February 7, 2024, via an oral presentation in the Clinical Applications session from 8:00-9:00 a.m. P.T. and a poster presentation from 3:00-5:00 p.m. P.T. (Poster Ref: 145). These data will also be available on Sangamo’s website on the Presentations page..

这些数据将于2024年2月7日（星期三）在加利福尼亚州圣地亚哥举行的第20届世界研讨会（WORLDSymposiumTM）上通过临床应用会议（上午8:00-9:00）的口头演示和下午3:00-5:00的海报演示进行共享（海报参考号：145）。这些数据也将在Sangamo网站的演示页面上提供。。

“Despite the availability of ERT and chaperone therapies, Fabry disease treatment is burdensome, with some patients still developing disease progression. To date, ST-920 has been well-tolerated, and the preliminary data showing sustained supraphysiologic α-Gal A activity and the ability to discontinue and remain off ERT are promising,” said Dr.

“尽管有ERT和伴侣疗法，法布里病的治疗仍然很繁重，一些患者仍在发展疾病进展。迄今为止，ST-920的耐受性良好，初步数据显示持续的超生理α-半乳糖A活性以及停止和停止ERT的能力是有希望的，”Dr。

Robert Hopkin, M.D., Cincinnati Children’s Hospital Medical Center, and investigator of the Phase 1/2 STAAR study. “The early improvements reported in disease severity, quality of life and gastrointestinal symptoms, together with evidence of reduced immunogenicity, illustrate the potential of ST-920 as a treatment option for adults with Fabry disease.”.

辛辛那提儿童医院医学中心医学博士罗伯特·霍普金（RobertHopkin）是STAAR 1/2期研究的研究员。“据报道，疾病严重程度，生活质量和胃肠道症状的早期改善，以及免疫原性降低的证据，说明了ST-920作为法布里病成人治疗选择的潜力。”。

“We remain encouraged by the emerging safety and efficacy data supporting the potential durable benefit that ST-920 could offer patients with Fabry disease as a convenient single-dose treatment option,” said Lisa Rojkjaer, M.D., Chief Medical Officer of Sangamo. “We expect to complete dosing of the remaining patients in the first half of this year as we continue to explore potential partnerships and other financing options to support the initiation of a registrational trial.”.

Sangamo首席医疗官LisaRojkjaer医学博士说：“我们仍然受到新出现的安全性和有效性数据的鼓舞，这些数据支持ST-920可以为法布里病患者提供潜在的持久益处，作为一种方便的单剂量治疗选择。”。“我们预计在今年上半年完成剩余患者的给药，因为我们将继续探索潜在的合作伙伴关系和其他融资选择，以支持注册试验的启动。”。

Updated Phase 1/2 STAAR Study Results

更新的1/2期STAAR研究结果

As of the September 19, 2023 data cutoff date, 24 patients had been dosed; as of the treatment date, 13 (54%) were on ERT and 10 (42%) had mild to moderate renal dysfunction at baseline.

截至2023年9月19日的数据截止日期，已有24名患者服用了药物；截至治疗日期，13例（54%）接受了ERT治疗，10例（42%）在基线时有轻度至中度肾功能不全。

Safety:

安全性：

Isaralgagene civaparvovec continued to be generally well-tolerated. The most common adverse events were pyrexia, headache, COVID-19, fatigue and nasopharyngitis (majority Grade 1/2, with one Grade 3 pyrexia).

Isaralgagene civaparvovec总体上耐受性良好。最常见的不良事件是发热，头痛，新型冠状病毒肺炎，疲劳和鼻咽炎（大多数1/2级，1级3级发热）。

No LFT elevations post-dosing requiring steroids occurred. No prophylactic steroids or other immunomodulatory agents were administered, as per protocol.

没有发生需要类固醇的给药后LFT升高。根据方案，未给予预防性类固醇或其他免疫调节剂。

Efficacy (all dosed patients):

疗效（所有给药患者）：

Patients treated in the dose escalation and dose expansion phases exhibited sustained, elevated expression of α-Gal A activity for up to three years in the longest treated patient.

在剂量递增和剂量扩展阶段接受治疗的患者，在接受治疗时间最长的患者中，α-半乳糖A活性的表达持续升高长达三年。

The ERT naïve or pseudo-naïve patients receiving the highest dose (2.63 x 1013) showed sustained supraphysiological α-Gal A activity up to nearly 500 days, with the largest reductions in plasma globotriaosylsphingosine (lyso-Gb3) levels seen in those subjects with the highest levels at baseline.

接受最高剂量（2.63 x 1013）的ERT初治或假初治患者表现出持续的超生理α-半乳糖A活性长达近500天，在基线水平最高的受试者中，血浆球三糖基鞘氨醇（lyso-Gb3）水平降低幅度最大。

All 12 patients who began the study on ERT and have subsequently been withdrawn from ERT, remained off ERT as of the September 19, 2023 data cutoff date. 11 of these patients continued to exhibit supraphysiological levels of α-Gal A activity for up to 19 months for the longest treated patient, with one patient maintaining physiological levels.

截至2023年9月19日的数据截止日期，所有12名开始ERT研究并随后退出ERT的患者均未接受ERT。对于治疗时间最长的患者，其中11名患者在长达19个月的时间内继续表现出超生理水平的α-半乳糖A活性，其中一名患者保持生理水平。

For the eight ERT-treated patients receiving the highest dose (2.63 x 1013), plasma lyso-Gb3 levels remained stable following ERT withdrawal for up to one year..

对于接受最高剂量（2.63 x 1013）的八名接受ERT治疗的患者，血浆lyso-Gb3水平在ERT停药长达一年后保持稳定。。

Progressive organ impairment linked to immunogenicity remains an issue with ERT. Seven patients had measurable titers of total antibodies (Ab) or neutralizing antibodies (Nab) against α-Gal A associated with ERT at baseline. Following dosing, total Ab or NAb titers decreased markedly in all seven patients and became undetectable in five, or 71% of patients.

与免疫原性相关的进行性器官损伤仍然是ERT的问题。七名患者在基线时具有可测量的针对与ERT相关的α-半乳糖A的总抗体（Ab）或中和抗体（Nab）滴度。给药后，所有七名患者的总Ab或NAb滴度均显着降低，而五名或71%的患者检测不到。

Isaralgagene civaparvovec did not induce anti-α-Gal A antibodies in seronegative patients..

Isaralgagene civaparvovec在血清阴性患者中未诱导抗α-GalA抗体。。

Efficacy (13 patients followed for 12 months or more):

疗效（13名患者随访12个月或更长时间）：

Renal function remained stable, as evidenced by a mean annualized estimated glomerular filtration rate (eGFR) slope of -0.915 mL/min/1.73m2/year.

肾功能保持稳定，平均年化估计肾小球滤过率（eGFR）斜率为-0.915 mL/min/1.73m2/年。

Statistically significant improvements in disease severity were reported in the Fabry Outcome Survey adaptation of the Mainz Severity Score Index (FOS-MSSI) age-adjusted score at week 52 (p=0.0269).

在第52周，法布里结局调查对美因茨严重程度评分指数（FOS-MSSI）年龄调整评分的适应性报告了疾病严重程度的统计学显着改善（p=0.0269）。

Four patients improved their overall FOS-MSSI disease category (e.g., improving from ‘Moderate’ to ‘Mild’ categorization of Fabry disease compared to their baseline category) at week 52. Three of these individuals were on ERT at baseline, demonstrating the potential clinical benefit of isaralgagene civaparvovec over the currently approved standard of care..

在第52周，四名患者改善了他们的整体FOS-MSSI疾病类别（例如，与基线类别相比，法布里病的“中度”到“轻度”分类有所改善）。其中三人在基线时接受了ERT治疗，证明了isaralgagene civaparvovec相对于目前批准的护理标准具有潜在的临床益处。。

Significant improvements in the short form-36 (SF-36) QoL scores were reported, with mean changes in the General Health and Physical Component scores of 10.5 (p=0.0158) and 4.395 (p=0.0140), respectively, at week 52. For context, a 3- to 5-point change on any SF-36 score is the minimally clinically important difference..

据报道，short form-36（SF-36）QoL评分显着改善，在第52周，一般健康和身体成分评分的平均变化分别为10.5（p=0.0158）和4.395（p=0.0140）。在上下文中，任何SF-36评分的3到5分变化都是临床上最小的重要差异。。

Significant improvements in the gastrointestinal symptom rating scale (GSRS) compared to baseline were also reported at week 52 (p=0.0226).

与基线相比，胃肠道症状评定量表（GSRS）在第52周也有显着改善（p=0.0226）。

Collectively, we believe these data support the potential for isaralgagene civaparvovec to be a promising new treatment option for previously treated and untreated patients with Fabry disease.

总的来说，我们相信这些数据支持isaralgagene civaparvovec成为先前治疗和未治疗的法布里病患者的有希望的新治疗选择。

Since the September 19, 2023 data cutoff date, four additional patients have been dosed in the expansion phase to achieve a total of 28 treated patients, and one additional patient has been withdrawn from ERT. All 13 patients withdrawn from ERT remain off ERT as of February 5, 2024. Screening and enrollment are complete in the Phase 1/2 STAAR study and dosing of the remaining enrolled patients is expected in the first half of 2024.

自2023年9月19日数据截止日期以来，又有四名患者在扩展阶段服用了药物，总共有28名患者接受了治疗，另外一名患者已退出ERT。截至2024年2月5日，所有13名退出ERT的患者仍不接受ERT。1/2期STAAR研究的筛查和登记已完成，剩余登记患者的剂量预计将在2024年上半年完成。

The Company is deferring additional investments in planning for a registrational trial until a collaboration partnership or financing is secured. Productive discussions continue with the U.S. FDA and other health authorities on pathways to registration..

该公司将推迟在注册试验计划中的额外投资，直到合作伙伴关系或融资得到保证。继续与美国FDA和其他卫生部门就注册途径进行富有成效的讨论。。

Additionally, another oral presentation and poster presentation at WorldSymposiumTM will feature pharmacology and safety data from the Company’s nonclinical work for isaralgagene civaparvovec. The data demonstrated supraphysiological plasma and liver α-Gal A activity in mouse models, supporting Phase 1/2 and potential Phase 3 clinical dosing.

此外，在WorldSymposiumTM上的另一次口头演示和海报演示将展示该公司为isaralgagene civaparvovec进行的非临床工作的药理学和安全性数据。数据显示小鼠模型中的超生理血浆和肝脏α-半乳糖A活性，支持1/2期和潜在的3期临床给药。

The oral presentation will take place at WORLDSymposiumTM on Thursday, February 8, 2024, in the Contemporary Forum session from 8:00-9:00 a.m. P.T. and a poster presentation will be from 3:00-5:00 p.m. P.T. (Poster Ref: 224)..

口头演示将于2024年2月8日（星期四）在当代论坛会议上于上午8:00-9:00进行，海报演示将于下午3:00-5:00进行（海报参考号：224）。。

A Current Report on Form 8-K summarizing the updated preliminary results from the Phase 1/2 STAAR study in more detail will be filed by Sangamo, and this press release is subject to the further detail provided in the Form 8-K.

Sangamo将提交一份表格8-K的最新报告，其中更详细地总结了1/2期STAAR研究的最新初步结果，本新闻稿以表格8-K中提供的更多细节为准。

About the STAAR Study

关于STAAR研究

The Phase 1/2 STAAR study is a global open-label, single-dose, dose-ranging, multicenter clinical study designed to evaluate the safety and tolerability of isaralgagene civaparvovec, or ST-920, a gene therapy product candidate in patients with Fabry disease. Isaralgagene civaparvovec requires a one-time infusion without preconditioning.

1/2期STAAR研究是一项全球开放标签，单剂量，剂量范围，多中心临床研究，旨在评估isaralgagene civaparvovec或ST-920（法布里病患者的基因治疗候选产品）的安全性和耐受性。Isaralgagene civaparvovec需要一次性输注而无需预处理。

The STAAR study enrolled patients who are on ERT, are ERT pseudo-naïve (defined as having been off ERT for six or more months), or who are ERT-naïve. The U.S. Food and Drug Administration has granted Orphan Drug, Fast Track and RMAT designations to isaralgagene civaparvovec, which has also received Orphan Medicinal Product designation from the European Medicines Agency..

STAAR研究招募了接受ERT治疗的患者，这些患者是ERT伪天真的（定义为停止ERT治疗六个月或更长时间）或未接受ERT治疗的患者。美国食品和药物管理局已授予isaralgagene civaparvovec孤儿药、快速通道和RMAT名称，isaralgagene civaparvovec还获得了欧洲药品管理局的孤儿药品名称。。

About Fabry Disease

关于法布里病

Fabry disease is a lysosomal storage disorder caused by mutations in the galactosidase alpha gene (GLA), which leads to deficient alpha-galactosidase A (α-Gal A) enzyme activity, which is necessary for metabolizing globotriaosylceramide (Gb3). The buildup of Gb3 in the cells can cause serious damage to vital organs, including the kidney, heart, nerves, eyes, gut and skin.

法布里病是由半乳糖苷酶α基因（GLA）突变引起的溶酶体贮积病，导致α-半乳糖苷酶a（α-GalA）酶活性不足，这是代谢球三糖神经酰胺（Gb3）所必需的。Gb3在细胞中的积累会对重要器官造成严重损害，包括肾脏、心脏、神经、眼睛、肠道和皮肤。

Symptoms of Fabry disease can include decreased or absent sweat production, heat intolerance, angiokeratoma (skin blemishes), vision problems, kidney disease, heart failure, gastrointestinal disturbance, mood disorders, neuropathic pain and tingling in the extremities..

法布里病的症状可能包括出汗减少或不出汗、热不耐受、血管角化瘤（皮肤瑕疵）、视力问题、肾脏疾病、心力衰竭、胃肠道紊乱、情绪障碍、神经性疼痛和四肢刺痛。。

About Sangamo Therapeutics

关于Sangamo Therapeutics

Sangamo Therapeutics is a genomic medicine company dedicated to translating ground-breaking science into medicines that transform the lives of patients and families afflicted with serious neurological diseases who do not have adequate or any treatment options. Sangamo’s zinc finger epigenetic regulators are ideally suited to potentially address devastating neurological disorders and Sangamo’s capsid discovery platform is making progress toward potentially expanding delivery beyond currently available intrathecal delivery capsids, including in the central nervous system.

Sangamo Therapeutics是一家基因组医学公司，致力于将开创性的科学转化为药物，以改变患有严重神经系统疾病但没有足够或任何治疗选择的患者和家庭的生活。Sangamo的锌指表观遗传调节剂非常适合潜在地解决毁灭性的神经系统疾病，Sangamo的衣壳发现平台正在朝着潜在的扩大递送的方向取得进展，超出目前可用的鞘内递送衣壳，包括中枢神经系统。

Sangamo’s pipeline also includes multiple partnered programs and programs with opportunities for partnership and investment. To learn more, visit www.sangamo.com and connect with us on LinkedIn and Twitter..

Sangamo的渠道还包括多个合作项目和有合作和投资机会的项目。要了解更多信息，请访问www.sangamo.com，并通过LinkedIn和Twitter与我们联系。。

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements regarding our current expectations. These forward-looking statements include, without limitation, statements relating to: the safety and efficacy and therapeutic and commercial potential of isaralgagene civaparvovec, the anticipated plans and timelines for conducting our ongoing and potential future clinical trials and presenting clinical data from our clinical trials, expectations regarding the conclusion of dosing in our Phase 1/2 STAAR study, the anticipated advancement of isaralgagene civaparvovec to late-stage development, including Sangamo’s plans to seek a potential partner or additional financing to proceed with potential future Phase 3 trials of isaralgagene civaparvovec and the timing thereof, our plans to participate in industry and investor conferences, and other statements that are not historical fact.

本新闻稿包含有关我们当前期望的前瞻性声明。这些前瞻性声明包括但不限于以下方面的声明：isaralgagene civaparvovec的安全性和有效性以及治疗和商业潜力，进行我们正在进行的和潜在的未来临床试验的预期计划和时间表，以及提供我们临床试验的临床数据，对我们的1/2期STAAR研究中给药结论的期望，Isaragagene civaparvovec向后期开发的预期进展，包括Sangamo计划寻求潜在合作伙伴或额外资金，以继续进行Isaragagene civaparvovec的潜在未来3期试验及其时间安排，我们计划参加行业和投资者会议，以及其他非历史事实的声明。

These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to our lack of capital resources to fully develop, obtain regulatory approval for and commercialize our product candidates, including our ability to secure the funding required to initiate a potential Phase 3 trial of isaralgagene civaparvovec in a timely manner or at all; our need for substantial additional funding to execute our operating plan and to continue to operate as a going concern; the effects of macroeconomic factors or financial challenges, including as a result of the ongoing overseas conflict, current or potential future bank failures, inflation and rising interest rates, on the global business environment, healthcare systems and business an.

这些声明并不能保证未来的业绩，并且会受到某些难以预测的风险和不确定性的影响。可能导致实际结果不同的因素包括但不限于与我们缺乏资本资源以充分开发，获得监管部门批准并将我们的候选产品商业化有关的风险和不确定性，包括我们能够及时或根本获得启动isaralgagene civaparvovec潜在3期试验所需的资金；我们需要大量额外资金来执行我们的运营计划并继续经营下去；宏观经济因素或金融挑战（包括持续的海外冲突、当前或潜在的未来银行倒闭、通货膨胀和利率上升）对全球商业环境、医疗保健系统和商业的影响。

There can be no assurance that we and our current or potential future collaborators will be able to develop commercially viable products. Actual results may differ materially from those projected in these forward-looking statements due to the risks and uncertainties described above and other risks and uncertainties that exist in the operations and business environments of Sangamo and our collaborators.

无法保证我们和我们目前或潜在的未来合作者能够开发出商业上可行的产品。由于上述风险和不确定性以及Sangamo和我们的合作者的运营和业务环境中存在的其他风险和不确定性，实际结果可能与这些前瞻性声明中预测的结果存在重大差异。

These risks and uncertainties are described more fully in our Securities and Exchange Commission, or SEC, filings and reports, including in our Annual Report on Form 10-K for the year ended December 31, 2022, as supplemented by our Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, each filed with the SEC, and future filings and reports that Sangamo makes from time to time with the SEC.

这些风险和不确定性在美国证券交易委员会（SEC）的文件和报告中有更全面的描述，包括截至2022年12月31日的10-K表格年度报告，以及截至2023年9月30日的10-Q表格季度报告，每个季度都提交给SEC，以及Sangamo不时向SEC提交的未来文件和报告。

Forward-looking statements contained in this announcement are made as of this date, and we undertake no duty to update such information except as required under applicable law..

本公告中包含的前瞻性声明自即日起发布，除适用法律要求外，我们不承担更新此类信息的义务。。