Table 2.

Estimated JNJ-8104, CNTO148 and CNTO 6785 cynomolgus monkey PK/TE model parameters (mean, residual standard error%) and predicted human parameters.

Parameter (unit)	JNJ-8104 Human, predicted (observed human PK)	JNJ-8104 Human, predicted (allometric scaling)	JNJ-8104 Cyno, estimated	Golimumab Cyno, estimated	CNTO 6785 Cyno, estimated
CL (L/day/kg)	0.00549	0.0048 *	0.0077 (4%)	0.0131 (10%)	0.0072 (14%)
V1 (L/kg)	0.0464	0.0375 *	0.0375 (5%)	0.0588 (4%)	0.0405 (6%)
V2 (L/kg)	0.0341	0.0217 *	0.0217 (9%)	0.0342 (9%)	0.0302 (5%)
Q (L/day/kg)	0.00598	0.0140 *	0.0224 (11%)	0.0353 (11%)	0.023 (9%)
TNFα
kdeg (1/day)	271.18 *	271.18 *	596 ●	596 ●
Baseline (pg/mL)	0.9^^	0.9^^	0.612 ^	0.612 ^
kel_complex (1/day)	0.12	0.17*	0.365 ●	0.365 ●
KD (pM)	1610 ʘ	1610 ʘ	1610 (10%)	65.7 (10%)
IL-17A
kdeg (1/day)	45.50 *	45.50 *	100 #		100 (31%)
Baseline (pg/mL)	1.365^^^	1.365^^^	0.763 (29%)		1.365 ^
kel_complex (1/day)	0.12	0.14 *	0.317 (25%)		0.504 (39%)
KD (pM)	254 ʘ	254 ʘ	254 (21%)		38.9 (41%)

The PK data points under apparent impact of ADA were excluded for estimating human PK parameters based on JNJ-61178104 observed PK in the FIH study.

k_{el_complex} was based on the estimated human PK parameters assuming that k_{el_complex} for both targets was the same as the elimination rate constant of JNJ-8104 (e.g., calculated as CL/V₁).

*Scaled from JNJ-8104 cyno parameters using BW-based allometric scaling with fixed exponents.

ʘ fixed at the estimated parameter values based on JNJ-8104 cyno model fitting.

^^ fixed at the reported population median value for TNFα baseline in RA patients.⁴⁰

^^^ assumed to be the same as cynos and fixed at the observed mean IL-17A baseline in cynos

● fixed based on mathematical derivations using observed data, see section “TMDD model for TNFα” for details.

^ fixed at the observed mean baseline levels for TNFα or IL-17A in cynos

# fixed at the estimated parameter value based on CNTO 6785 cyno model fitting.