Sangamo Therapeutics, Inc. · NASDAQ:SGMO
Sangamo Therapeutics — Technical Presentation (December 2024)
16 slides from Sangamo Therapeutics's technical presentation, Dec 10, 2024
Slide 1: Efficacy and Safety of Giroctocogene Fitelparvovec in Hemophilia A: AFFINE Primary Analysis
1 1053 Efficacy and Safety of Giroctocogene Fitelparvovec in Adults With Moderately Severe to Severe Hemophilia A: Primary Analysis Results From the Phase 3 AFFINE Gene Therapy Trial Andrew D Leavitt1, Kaan Kavakli2, Laurent Frenzel3, Ali Bülent Antmen4, Margareth Ozelo5, Davide Matino6,7, Hazza Alz
Slide 2: Giroctocogene fitelparvovec for hemophilia A
22 • Liver-tropic recombinant AAV serotype 6 (rAAV6) vector carrying B-domain–deleted human F8 transgene enabling endogenous FVIII expression in individuals with severe to moderately severe hemophilia A • The completed Alta phase 1/2 dose-ranging study1,2 (up to 5 years) demonstrated a single infusi
Slide 3: AFFINE study design
33 AFFINE study design AAV-6=adeno-associated virus serotype 6; ABR=annualized bleeding rate; AIR=annualized infusion rate; FVIII=factor VIII; NAb=neutralizing antibody; vg=vector genome Primary endpoint • ABR for total bleeds (treated and untreated) from Week 12 through ≥15 months Key secondary end
Slide 4: Participant disposition
44 Participant disposition a anti-AAV-6 NAb titer ≥1:4. AAV-6=adeno-associated virus serotype 6; NAb=neutralizing antibody AFFINE SCREENING PHASE N=82 enrolled N=77 selected for treatment AFFINE PHASE 3 STUDY N=75 dosed N=75 ongoing in the follow-up phase AFFINE Efficacy Population n=50 LEAD-IN STUD
Slide 5: Baseline demographics and characteristics
Baseline demographics and characteristics a n (%) unless otherwise noted. BMI=body mass index 5 n (%)a N=75 Region North America 12 (16.0) Europe 19 (25.3) Middle East 30 (40.0) Asia Pacific 10 (13.3) South America 3 (4.0) Australia 1 (1.3) Ongoing controlled HIV 6 (8.0) History of hepatitis B 11 (1
Slide 6: Annualized bleeding rate: Total (treated and untreated) bleeds
66 Annualized bleeding rate: Total (treated and untreated) bleeds Numbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participa
Slide 7: Annualized bleeding rate: Total (treated and untreated) bleeds
7 0 2 4 6 8 1.24 4.73 4.65 M ea n AB R e st im at e (u pp er b ou nd o f 9 5% C I) Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) ABRtotal (n=50) ABRtotal (n=49) -3.49 (-6.06, -0.91) P=0.004 -4.40 (-6.31, -2.48) P<0.0001 0.26 7 Annualized bleeding rate: Total (treated an
Slide 8: Annualized bleeding rate: Total (treated and untreated) bleeds
0 2 4 6 8 1.24 4.73 4.65 M ea n AB R e st im at e (u pp er b ou nd o f 9 5% C I) Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) ABRtotal (n=50) ABRtotal (n=49) -3.49 (-6.06, -0.91) P=0.004 -4.40 (-6.31, -2.48) P<0.0001 0.26 8 Annualized bleeding rate: Total (treated and
Slide 9: Annualized bleeding rate: Treated bleeds
99 Annualized bleeding rate: Treated bleeds Numbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participant as a random effect
Slide 10: Annualized infusion rate of exogenous FVIII
Annualized infusion rate of exogenous FVIII The mean difference (95% CI) and 1-sided P-value were obtained from paired t-test. AIR=annualized infusion rate; FVIII=factor VIII; SD=standard deviation 10 Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) 0 50 100 150 200 124.39
Slide 11: FVIII activity levels post infusion
FVIII activity levels post infusion CA=chromogenic assay; FVIII=factor VIII; LLOQ=lower limit of quantification 11 At Month 15, 84% (95% CI 70.9, 92.8) of participants in the Efficacy Population (n=50) had FVIII activity levels >5% (via CA); 1-sided P=0.0086 vs null hypothesis of ≤68% Week 12 Month
Slide 12: FVIII activity levels through Year 3
12 FVIII activity levels through Year 3 Values >300% not shown. CA=chromogenic assay; BLOQ=below lower limit of quantification; FVIII=factor VIII; IQR=interquartile range; max=maximum; min=minimum; Q=quartile Fa ct or V III A ct iv ity (c hr om og en ic , % ) Post infusion (Weeks) 50% 5% Year 2 51.9
Slide 13: Safety summary: adverse events
13 • No infusion interruptions or rate slowing • Infusion-related reactions (events occurring within 2 days post infusion) in 58 (77.3%) participants – Mostly mild (n=39/58; 67.2%) with resolution within 2 days • At data cutoff (mean [range] follow-up, 21.88 [7.8-44.4] months): – No FVIII inhibitors
Slide 14: ALT and corticosteroid use
14 • ALT elevations were mild and manageable – ALT elevations resolved within a median of 28.0 days • Overall, corticosteroids were well tolerated, with corticosteroid-related AEs reported in 19 (25.3%) participants • At the time of the data cutoff, no participants in the Efficacy Population remaine
Slide 15: FVIII elevations and DOAC use
15 • DOACs were well tolerated, with no significant bleeding events while on DOAC – In total, 6 participants reported ≥1 bleed while on DOAC, none were treated • 1 participant (major PD with prior history of DVT and PE and multiple thrombotic risk factors) experienced a thromboembolic event • No oth
Slide 16: Summary: Efficacy and safety of giroctocogene fitelparvovec
16 • A single IV infusion of 3e13 vg/kg was generally well tolerated and exhibited an acceptable and manageable safety profile • The study met the primary endpoint with a significantly reduced mean ABRtotal vs FVIII prophylaxis: 1.24 vs 4.73 (0.26 vs 4.65 in post hoc sensitivity analysis) • Mean ABR
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