Sangamo Therapeutics, Inc. · NASDAQ:SGMO
Sangamo Therapeutics — 65th Annual Meeting and Exposition of the American Society of Hematology (ASH) 2023
14 slides from Sangamo Therapeutics's conference presentation, Dec 13, 2023
Slide 1: Four-Year Follow-up of the Alta Study of Giroctocogene Fitelparvovec in Severe Hemophilia A
1 65th Annual Meeting and Exposition of the American Society of Hematology (ASH) , December 9–12, 2023, San Diego, CA, USA Four-Year Follow-up of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (PF-07055480/SB-525) Gene Therapy in Adults With Severe Hemophilia A Thomas J Harrington1
Slide 2: Hemophilia A
2 • A rare bleeding disorder caused by pathogenic variants in the F8 gene, resulting in insufficient FVIII activity • Current treatment involves replacement therapy with exogenous FVIII or with emerging mimetic-based bispecific antibody therapy, both requiring frequent dosing via IV or SC administra
Slide 3: Giroctocogene fitelparvovec gene therapy for hemophilia A
3 • AAV-vector–mediated gene transfer enables the delivery of a modified functional F8 coding sequence to hepatocytes that subsequently synthesize FVIII at levels that may prevent bleeding events in the absence of exogenous FVIII • Giroctocogene fitelparvovec (formerly SB-525 or PF-07055480) is a li
Slide 4: Alta: Study population and design
4 • Phase 1/2, single-dose, multicenter, dose-ranging study to assess the safety and tolerability of giroctocogene fitelparvovec in adults (aged ≥18 years) with severe hemophilia A Alta: Study population and design AAV6=adeno-associated virus serotype 6; FVIII=factor VIII Key Exclusion Criteria • Ne
Slide 5: Alta: Endpoints
5 Alta: Endpoints AE=adverse event; FVIII=factor VIII; SAE=serious adverse event • Incidence of AEs and SAEs • Change in circulating FVIII activity Primary Endpoints • Change from baseline in the use of FVIII replacement therapy • Change in frequency and severity of bleeding episodes • Measurement o
Slide 6: Alta: Participant demographic characteristics
6 Characteristic Cohort 1 9e11 vg/kg n=2 Cohort 2 2e12 vg/kg n=2 Cohort 3 1e13 vg/kg n=2 Cohort 4 3e13 vg/kg n=5 All Participants N=11 Age, years Mean (SD) 30.5 (9.2) 35.5 (16.3) 32.0 (1.4) 26.8 (6.3) 30.0 (7.9) Median 30.5 35.5 32.0 29.0 30.0 Min, max 24, 37 24, 47 31, 33 18, 34 18, 47 Sex, n (%) M
Slide 7: Alta: Follow-up duration
7 11 participants were dosed, all completed 3 years (156 weeks) follow-up 4 completed 5 years, 5 completed 4 years, 2 left the study after 3 years, 1 was lost to follow-up (in Year 5) Alta: Follow-up duration ǂ Participant lost to follow-up. * Participants did not consent to continued follow-up afte
Slide 8: Alta: Treatment-related adverse events
8 MedDRA Preferred Term Cohort 2 2e12 vg/kg n=2 Cohort 4 3e13 vg/kg n=5 All Participants N=11 n (%) No. of Events n (%) No. of Events n No. of Events Any treatment-related event 2 (100) 5 4 (80) 22 6 (55) 27 Grade 3/4 AE 0 0 1 (20)a 1 1 (9) 1 ALT increasedb 2 (100) 3 3 (60) 10 5 (46) 13 AST increase
Slide 9: Alta: Safety summary
9 • A total of 116 treatment-emergent AEs (all causalities) occurred in 11 participants • 27 treatment-related AEs occurred in 6 participants; the most common were: – ALT increase: 13 events in 5 participants (Cohorts 2 and 4) – AST increase: 5 events in 3 participants (Cohorts 2 and 4) • 4 of 5 par
Slide 10: Alta: FVIII activity
10 Alta: FVIII activity (Cohort 4 participants) Mild range: >5% to <40%; normal range: >50%. Latest available FVIII values from September 2023 data cut. FVIII=factor VIII. FVIII Activity, as Measured at Central Laboratory with Chromogenic Assay 5% 50% 100% Study Week Week 78 n=4 Week 104 n=5 Week 13
Slide 11: Alta: ABR and AIR (Cohort 4 participants)
11 Post-infusion: Mean overall ABR = 1.4 Median overall ABR = 0.0 Post-infusion: Mean overall AIR = 5.0 Median overall AIR = 0.4 Alta: ABR and AIR (Cohort 4 participants) ABR calculated as: (number of all bleeding episodes starting 3 weeks after study drug infusion)/(observation period in years). AI
Slide 12: Alta: Bleeding events and FVIII maintenance in Cohort 4
12 • 0 bleeding events occurred in the first year post infusion • Median and mean (SD) ABR = 0.0 and 1.4 (2.82) for total duration of follow-up (n=5 participants with ≥3 years of follow-up) • 3 of 5 participants (60%) experienced no bleeds • 2 participants experienced bleeding events necessitating t
Slide 13: Conclusions
13 • A single infusion of giroctocogene fitelparvovec gene therapy in participants with severe hemophilia A was generally well tolerated, with associated increases in FVIII levels, transient AEs, and mean ABR of 1.4 in the highest-dose cohort (3e13 vg/kg) • Additional follow-up is required to assess
Slide 14: Acknowledgments
14 • The investigators acknowledge and thank all study participants. We also thank the site staff and the Sangamo and Pfizer Study Teams for their contributions and for the conduct of the trial. • This study was funded by Pfizer. • Medical writing support was provided by Courtney Cameron, PhD, of En