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Pharma Update

SPK-8011 in hem A: Durable FVIII activity observed up to 5 years FVIII activity accompanied by durable clinical benefit in ABR, joint health and quality of life Study design 5 1011 vg/kg (n=2) 1 1012 vg/kg (n=3) 2 1012 vg/kg (n=9) 1.5 1012 vg/kg (n=10) 1-hour outpatient IV infusion* 52 (+2) weeks 4-year long-term follow-up period (n=24) follow up study: visits every 3-6 months (n=18) Mean FVIII activity OSA (%) Roche FDA BTD Stable FVIII activity levels and improved QoL over long-term follow-up Mean FVIII activity OSA 50 1.5x1012 vg/kg 5x1011 vg/kg 1x1012 vg/kg 2x1012 vg/kg 35 30 15 10 4422250 5 0 >52-104 >104-156 >156-208 >208 Time after vector administration (weeks) Mean (SD) change in Haem-A-QoL TS Change in Haem-A-QoL total score from baseline Year 1 Year 2 Year 3 5050522 -30 -12.3 (16.3) -11.3 -13.4 (15.8) (13.0) n=16 n=15 n=13 Efficacy and safety of single SPK-8011* infusion: • 16 participants with ≥1 year follow-up showed no apparent decrease in FVIII activity over time, with a majority expressing in the mild HA range • 82-99% reductions in ABR and substantial reductions in FVIII consumption, no major safety signals • • Clinically meaningful improvements in joint health by total HJHS score at Year 2 and 3 and in total Haem-A-QoL at Years 1, 2, and 3 Ph III study to open enrolment in 2H 2023 © dirloctocogene samoparvovec; Croteau et al ASH 2022; Data cut-off: Oct 4 2022; analysis includes participants with >52 weeks of follow up (n=16). Grey shaded area indicates the mild range of hemophilia A; FVIII assessments obtained within 5 days of administration of a FVIII infusion were excluded; OSA-one-stage assay; FVIII:C=FVIII coagulant activity; HA=hemophilia A; QoL-Quality of life; ABR=Annualized bleeding rate; M.V. Ragni et al., ISTH 2023, B. Samelson-Jones et al., ISTH 2023 97 97
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