Agalsidase Beta

STAAR study demonstrated positive mean annualized estimated glomerular filtration rate (eGFR) slope at 52-weeks across all dosed patients in the study, which U.S. Food and Drug Administration (FDA) has agreed will serve as primary basis of approval Isaralgagene civaparvovec showed a favorable safety and tolerability profile Sangamo intends to submit a Biologics License Application (BLA) in 2026 RICHMOND, CA, USA I June 24, 2025 I Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced positive topline results from the registrational Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, or ST-920, a wholly owned investigational gene therapy for the treatment of adults with Fabry disease. Following a single dose of isaralgagene civoparvovec, a positive mean annualized eGFR slope of 1.965 mL/min/1.73m 2 /year (95% confidence interval (CI): -0.153, 4.083) at 52-weeks was observed across all 32 dosed patients in the study, which the FDA has agreed will serve as an intermediate clinical endpoint under the Accelerated Approval pathway. Furthermore, a mean annualized eGFR slope of 1.747 mL/min/1.73m 2 /year (95% CI: -0.106, 3.601) was observed for the 19 patients who have achieved 104-weeks of follow-up. As recommended by the FDA, Sangamo plans to compare the annualized mean eGFR slope of isaralgagene civaparvovec with approved treatments for Fabry disease by performing a meta-analysis of published studies. According to observational studies, estimated mean annualized eGFR slopes for other marketed treatment options range from -2.2 to -0.4 mL/min/1.73m 2 /year for treatments such as Replagal (agalsidase alfa) 1 , Fabrazyme (agalsidase beta) 2 and Galafold (migalastat) 3 . We believe these data support the potential for isaralgagene civaparvovec as a one-time, durable treatment for Fabry disease that can improve patient outcomes and will form the basis for an anticipated BLA submission under the Accelerated Approval pathway as early as the first quarter of 2026. The STAAR study enrolled male and female patients who were either on enzyme replacement therapy (ERT), were ERT pseudo-naïve (defined as having been off ERT for six or more months), or were ERT-naïve. The median age of patients enrolled in the study was 42, with a median duration of follow-up of 24 months and the longest treated patient having achieved 4.5 years of follow-up. Key secondary endpoints in the study were also positive. Elevated expression of alpha-galactosidase A (α-Gal A) activity was maintained for up to 4.5 years for the longest treated patient. All 18 patients who began the study on ERT have been withdrawn from ERT and all remain off ERT as of today. Plasma lyso-Gb3 levels in these patients remained generally stable following ERT withdrawal. A stabilization in cardiac endpoints was also observed. Patients demonstrated a range of other clinical benefits, including improvements in disease severity reported in the Fabry Outcome Survey adaptation of the Mainz Severity Score Index (FOS-MSSI) age-adjusted score and statistically and clinically significant improvements in the short form-36 (SF-36) quality of life scores, including role-physical +14.8 (95% CI: 7.3, 22.4, p=0.0003), vitality +9.6 (95% CI: 3.9, 15.2, p=0.0017), bodily pain +9.0 (95% CI: 2.3, 15.7, p=0.0104), social functioning +7.8 (95% CI: 2.0, 13.6, p=0.0100), general health +7.4 (95% CI: 2.0, 12.8, p=0.0091), and physical component scores +4.2 (95% CI: 1.8, 6.6, p=0.0014), at week 52 compared to baseline. Statistically significant improvements in the gastrointestinal symptoms rating scale (GSRS) compared to baseline were also observed. Furthermore, following a single administration of isaralgagene civaparvovec, additional clinical benefits were observed in some patients, such as the reduction or elimination in pain medication usage and the resumption of sweating, that has enabled these patients to perform physical tasks and exercise. Isaralgagene civaparvovec demonstrated a favorable safety and tolerability profile in the study, without the requirement for preconditioning. The majority of adverse events were grade 1-2 in nature. The most common treatment-emergent adverse events (TEAEs) were pyrexia (60.6% of participants), COVID-19 (36.4%), headache (33.3%) and nasopharyngitis (33.3%). All TEAEs resolved in response to clinical management and there were no safety-related study discontinuations. “Fabry disease is a debilitating and multifaceted condition, for which there is a serious unmet medical need,” said Nathalie Dubois-Stringfellow, Ph. D, Chief Development Officer at Sangamo. “We are thrilled to see these compelling topline STAAR study results, including the positive mean annualized eGFR slope at both 52 and 104 weeks, alongside notable improvements in a range of secondary endpoints. Taken together these data demonstrate the potential for a single dose of ST-920 to provide meaningful clinical benefits above current standards of care and to treat the underlying pathology of Fabry disease. We want to thank the patients and investigators who participated in this study and look forward to sharing these data with health authorities.” Isaralgagene civaparvovec has been granted Orphan Drug, Fast Track and RMAT designations from the FDA, Orphan Medicinal Product designation and PRIME eligibility from the European Medicines Agency and Innovative Licensing and Access Pathway from U.K. Medicines and Healthcare products Regulatory Agency. Analyses of the full dataset from the STAAR study are ongoing and additional data will be presented at an upcoming medical meeting. Sangamo is advancing BLA preparation activities for isaralgagene civaparvovec, while continuing to engage in business development negotiations for a potential Fabry commercialization agreement. About the STAAR Study The Phase 1/2 STAAR study is a global open-label, single-dose, dose-ranging, multicenter clinical study designed to evaluate isaralgagene civaparvovec, or ST-920, a gene therapy product candidate in patients with Fabry disease. Isaralgagene civaparvovec requires a one-time infusion without preconditioning. About Fabry Disease 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. 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. About 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 believes that its zinc finger epigenetic regulators are ideally suited to potentially address devastating neurological disorders and that its capsid discovery platform can expand delivery beyond currently available intrathecal delivery capsids, including the central nervous system. 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 X . 1 Replagal (agalsidase alfa) estimated mean annualized eGFR slope: -2.2 mL/min/1.73m 2 /year (95% CI: -2.8, -1.7) in male patients and -0.7 mL/min/1.73m2/year (95% CI: -1.4, 0) in female patients (Source: Feriozzi, 2012: The effectiveness of long-term agalsidase alfa therapy in the treatment of Fabry nephropathy) 2 Fabrazyme (agalsidase beta) estimated mean annualized eGFR slope: -1.5 mL/min/1.73m 2 /year (Source: Fabrazyme Package Insert: https://products.sanofi.us/fabrazyme/fabrazyme.pdf ) 3 Galafold (migalastat) estimated mean annualized eGFR slope: -0.4 mL/min/1.73m 2 /year (95% CI: -2.27, 1.48) (Source: Hughes, 2016: Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomized phase III ATTRACT study) SOURCE: Sangamo Therapeutics

As Sangamo prepares for an FDA submission, the biotech said it\'s “continuing to engage in business development negotiations for a potential Fabry commercialization agreement.\"\n Sangamo Therapeutics’ investigational gene therapy appears to improve kidney function at 52 weeks for patients with a rare genetic disorder. The biotech plans to use the data for an FDA submission next year via the agency\'s accelerated approval pathway.The topline results come from a registrational phase 1/2 trial, dubbed STAAR, and include data from 32 patients with Fabry disease, a rare lysosomal storage disorder.The open-label study is evaluating a one-time infusion of isaralgagene civaparvovec, also known as ST-920. Some patients were on enzyme replacement therapy (ERT), while others had been off ERT for six or more months and some had never received the therapy.The trial demonstrated a mean annualized estimated glomerular filtration rate (eGFR) slope of 1.965 mL/min/1.73m2/year at 52 weeks across all dosed patients, according to a June 24 release.For 19 patients with two years of follow-up, the mean annualized eGFR slope was 1.747 mL/min/1.73m2/year.The FDA has previously agreed that the measure, a surrogate for renal function over time, can serve as an intermediate clinical endpoint for an accelerated approval submission from Sangamo. In the past, the agency has accepted eGFR slope as a way to measure the rate of decline in kidney function.Sangamo, for its part, believes the data \"support the potential for isaralgagene civaparvovec as a one-time, durable treatment for Fabry disease that can improve patient outcomes,\" according to the company\'s press release. In the company\'s most recent annual report, Sangamo said prior results from the trial showed \"notable improvements in renal function\" based on the eGFR slope measure.All 18 patients who started the study on ERT have stopped and remain off the therapy. A stabilization in cardiac endpoints was also recorded, according to the biotech.The gene therapy, which doesn’t require preconditioning, demonstrated a favorable safety and tolerability profile, according to Sangamo. Most adverse events were mild, and the most common treatment-emergent adverse events were fever and COVID-19. No safety-related study discontinuations were reported. Next, Sangamo will compare the eGFR slope data against approved Fabry treatments by performing a meta-analysis of published studies. Estimated mean annualized eGFR slopes for Takeda’s Replagal, Sanofi’s Fabrazyme and Amicus Therapeutics’ Galafold range from -2.2 to -0.4 mL/min/1.73m2/year, according to Sangamo.The California biotech plans on filing a biologics license application as early as the first quarter of 2026, according to the release. Sangamo’s gene therapy has garnered orphan, fast track and regenerative medicine advanced therapy tags from the FDA.Additional analyses of the full STAAR dataset will be presented at an upcoming medical meeting, the biotech said.As Sangamo prepares for an FDA submission, the biotech is “continuing to engage in business development negotiations for a potential Fabry commercialization agreement,” according to the release. A partner appears necessary for the cash-strapped company to bring the gene therapy to the finish line. Sangamo started 2025 with a stock crash driven by Pfizer terminating a hemophilia A gene therapy deal, which eliminated the potential for the biotech to collect up to $220 million in biobucks. The news came on top of Sangamo’s November 2024 announcement that it only had enough money in the bank to last until the first quarter of 2025. Luckily for Sangamo, Eli Lilly inked an $18 million upfront deal this April to use the biotech\'s neurotropic adeno-associated virus capsid in hopes of developing a gene therapy for a central nervous system disease. The pact gives Sangamo the chance to earn up to $1.4 billion as the entire gene therapy field faces a deep reckoning.   As of March 31, Sangamo had $25.1 million in cash and cash equivalents, according to a May 12 earnings release. That money, combined with the upfront cash from Lilly, is expected to fund operations into the third quarter of 2025, the biotech said.