Sangamo Therapeutics Announces Updated Phase 1/2 STAAR Study Data in Fabry Disease Showing Sustained Benefit and Differentiated Safety Profile - Seite 2

• 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.
• 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.
• All 12 patients who began the study on ERT and have subsequently been withdrawn from ERT, remained off ERT as of the September 19, 2023 data cutoff date. 11 of these patients continued to exhibit supraphysiological levels of α-Gal A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. 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.
• 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. Isaralgagene civaparvovec did not induce anti-α-Gal A antibodies in seronegative patients.

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

• Renal function remained stable, as evidenced by a mean annualized estimated glomerular filtration rate (eGFR) slope of -0.915 mL/min/1.73m²/year.
• 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).
• 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.
• 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.
• Significant improvements in the gastrointestinal symptom rating scale (GSRS) compared to baseline were also reported at week 52 (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.

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. 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.