Sangamo Therapeutics, Inc. · NASDAQ:SGMO
Sangamo Therapeutics — Technical Presentation (January 2021)
16 slides from Sangamo Therapeutics's technical presentation, Jan 14, 2021
Slide 1: Update for the Alta Study, a Phase 1/2 Gene Therapy Trial of Giroctocogene Fitelparvovec
Update for the Alta Study, a Phase 1/2 Gene Therapy Trial of Giroctocogene Fitelparvovec (SB-525) in Adults With Severe Hemophilia A Andrew D. Leavitt, MD1; Barbara A. Konkle, MD2,3; Kimo Stine, MD4; Nathan Visweshwar, MD5; Thomas J. Harrington, MD6; Adam Giermasz, MD, PhD7; Steven Arkin, MD8; Annie
Slide 2: Disclosures for Andrew D. Leavitt, MD
Disclosures for: Andrew D. Leavitt, MD Conflict Disclosure Research Support None Director, Officer, Employee None Shareholder Johnson & Johnson Honoraria None Advisory Committee BioMarin; Dova Pharmaceuticals; Catalyst Biosciences; Bio Products Laboratory Consultant Merck
Slide 3: Hemophilia A
A bleeding disorder due to low circulating factor VIII (FVIII) activity levels secondary to F8 gene mutations Current treatment involves replacement therapy with exogenous FVIII, or with emerging mimetic-based therapy Current treatment require frequent dosing via intravenous (IV) or subcutaneous adm
Slide 4: Giroctocogene Fitelparvovec Gene Therapy for Hemophilia A
Giroctocogene Fitelparvovec Gene Therapy for Hemophilia A Giroctocogene fitelparvovec (formerly SB-525 or PF-07055480) is a liver-tropic rAAV6 vector carrying a B-domain–deleted F8 gene that is delivered through a single IV infusion bp, base pairs; ITR, internal tandem repeat; IV, intravenous; rAAV6
Slide 5: Alta Study Design
Alta Study Design Alta is a phase 1/2, dose-ranging, single-dose, multicenter study to assess the safety and tolerability of giroctocogene fitelparvovec in adult participants (aged ≥18 years) with severe hemophilia A Participant Time in Study: 62 months Key Exclusion Criteria Neutralizing activity t
Slide 6: Study End Points
Study End Points Primary end points Incidence of AEs and SAEs Change in circulating FVIII activity Secondary end points Change from baseline for FVIII replacement therapy Change in frequency and severity of bleeding episodes Measurement of FVIII inhibitor levels Vector shedding in bodily fluids AE,
Slide 7: Study Design
Study Design 4 dose cohorts, 2 participants each, and a high-dose cohort expansion of 3 participants (total of 11 participants dosed) with reactive corticosteroid use Corticosteroid treatment is initiated for ALT elevation that exceeds 1.5x baseline value Safety and efficacy data of each cohort were
Slide 8: Participant Demographics
Characteristic Cohort 1 9e11 vg/kg Cohort 2 2e12 vg/kg Cohort 3 1e13 vg/kg Cohort 4 3e13 vg/kg All Participants Age, years n 2 2 2 5 11 Mean (SD) 30.5 (9.19) 35.5 (16.26) 32.5 (0.71) 27.2 (6.10) 30.3 (7.81) Median 30.5 35.5 32.5 29.0 31.0 Min, max 24, 37 24, 47 32, 33 19, 34 19, 47 Sex, n (%) Male 2
Slide 9: Safety Summary
Safety Summary 26 treatment-related AEs occurred in 6 participants, with most common being: ALT: 13a events in 5 participants (cohorts 2 and 4) AST: 5 events in 3 participants (cohorts 2 and 4) 1 participant in cohort 4 (3e13 vg/kg) experienced treatment-related SAEs of grade 3 hypotension and grade
Slide 10: Treatment-Related Adverse Events
Treatment-Related Adverse Events MedDRA Preferred Term Cohort 2 2e12 vg/kg (n=2) Cohort 4 3e13 vg/kg (n=5) All Participants (N=11) Subjects, n (%) No. of Events Subjects, n (%) No. of Events Subjects, n (%) No. of Events Any treatment-related event 2 (100.0) 5 4 (80.0) 21 6 (54.4) 26 ALT increaseda
Slide 11: ALT Elevations: Cohort 4 (3 x 10^13 vg/kg)
ALT Elevations: Cohort 4 (3 x 1013 vg/kg) Participant ID Number Time of First ALT Elevation (Week) Maximum ALT Value, U/L (Grade) Cortico-steroid Treatment Duration (Weeks) FVIII Levels (Chromo, IU/dL) at Start of Cortico-steroids FVIII Levels (Chromo, IU/dL) at End of Taper Time of Second ALT Eleva
Slide 12: Efficacy – Cohort (3e13 vg/kg)
Efficacy – Cohort 4 (3e13 vg/kg) Latest available FVIII values from August 2020 data cut. FVIII Activity as Measured at Central Laboratory With Chromogenic Assay FVIII, factor VIII; vg, vector genomes.
Slide 13: Efficacy – Central Laboratory, Chromogenic Assay
Efficacy – Central Laboratory, Chromogenic Assay Week 52: n=4 participants 1 participant had FVIII measured at week 67 instead of week 52 due to COVID-19 restrictions Mean FVIII activity from week 9 to week 52 (based on group mean): 70.4% (SD=7.3%) Median FVIII activity from week 9 to week 52 (based
Slide 14: Efficacy Summary
Efficacy Summary FVIII activity increase from baseline was generally dose dependent At 24 months, 1 participant in Cohort 3 remains in the mild range for factor VIII activity Cohort 4 (3e13 vg/kg) Steady-state FVIII activity achieved by week 9 post infusion Median steady-state (of geometric means fr
Slide 15: Conclusions
Conclusions Interim data with at least 1 year and up to 3 years of follow up post infusion continue to show that giroctocogene fitelparvovec is generally well tolerated 1 participant experienced treatment-related SAE immediately following vector infusion, no additional treatment-related SAE Cohort 4
Slide 16: Acknowledgments
The investigators acknowledge and thank all study participants. We also acknowledge and thank Pfizer Study Clinicians Delphine Agathon and Anne Yver for their work on this presentation and this study, as well as the site staff, and Sangamo and Pfizer Study Teams for their contributions and conduct o
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