Table 1. Characteristics of Patients at Screening and after Gene Transfer.

Participants	1	2	3	4	5	6	7	8	9	10
Dose level (vg/kg)	Low (2x1011)		Intermediate (6x1011)		High (2x1012)
Age at study entry (years)	31	64	43	29	32	27	22	38	44	33
FIX Mutation	31280 G>A E387K	2bp del. Frame shift	30097 G>T W215C	31290 G>A A309T	20518 C>T R180W	-52 del C	3bp del Frame shift	1277 C>T T426I	698 C>A A233D	385 G>T G129X
CRM status	Pos	Neg	Pos	Pos	Pos	Neg	Neg	Pos	Pos	Neg
Prophylaxis before gene therapy	2X/week	2X/week	2X/week	1X/week	2X/week	3X/week	1X/week	On- demand	On- demand	On- demand
No of target joints	4	10	6	3	10	2	2	4	5	3
Infection markers
Hepatitis B surface antigen	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg
Hepatitis B surface antibody	Pos	Pos	Pos	Pos	Pos	Pos	Neg	Pos	Pos	Pos
HIV antibody	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg
Hepatitis C antibody	Neg	Pos	Pos	Neg	Pos	Neg	Pos	Pos	Pos	Pos
Hepatitis C RNA	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg
Anti-AAV8 IgG antibody (Relative units)	1	12	37	1	5	8	1	6	6	5
Post gene transfer assessment
Steady state FIX activity IU/dL±SD)d	1.9±0.7	1.5±0.7	2.7±1.3	1.9±0.8	3.0±1.4	5.8±2.0	4.9±0.7	7.0±1.0	5.5±1.3	2.7±1.9
Elevation of ALT between weeks 1 and 12 post infusion)	No	No	No	No	Yes (week 7)	Yes (week 9)	Yes (week 8)	No	No	Yes (week 9)
Elevation of ALT between week 13 and 10 years post infusion	No	No	No	No	No	No	No	No	No	No
FIX inhibitor	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg	Neg
Follow-up period (years)	13.75	13.42	13.25	13.17	13	12.92	11.83	11.58	11.33	11.08
Annual usage of FIX concentrate
Pre-gene transfer (IU/Kg)	3608a	4284 a	2486 a	1515 a	2678 a	2509 a	5719 b	3130 a	1367 b	1714b
Post gene transfer (IU/Kg)	798	3559	2723	17	1863	35	497	237	45	106
Annual bleeding rate
Prior to gene transfer	3a	13a	12a	12a	15c	3.3 c	22b	20b	36b	29b
Mean ABR post gene transfer	1.9	4.6	1.9	0.7	5.5	0.3	2.3	0.9	1.1	0.2

vg = vector genome copies, kg = kilogram, FIX = factor IX, CRM = cross-reacting material (CRM+ patients have near normal levels (at least 30%) of dysfunctional protein in their plasma. FIX antigen is not detectable in CRM-patients.), HIV = human immunodeficiency virus, AAV8 = adeno-associated viral vector subtype 8, IgG = immunoglobulin G, SD = standard deviation, ALT = alanine aminotransferase, ± = plus or minus.

^aAverage of two years

^bone year

^cthree years of data.

^dSteady state FIX activity and antigen levels were defined as the mean of all levels obtained from 4 months after gene transfer through the December 31, 2023, and where, in each case, the most recent dose of recombinant FIX protein was at least ten days prior.