Anti-CFD Therapeutic Antibody (Lampalizumab)

Figure 1 Simulations of free target suppression in vitreous humor expressed as ratio of free target to baseline over time.

Solid black line represents the model-predicted vitreous humor free target ratio (FTR) for a typical patient in the CFD4870g study. Shaded region represents the 5th−95th prediction interval. Red, blue, and black lines denote the minimum FTR at 4, 6, and 8 weeks following intravitreal (ITV) lampalizumab administration. Black lines denote trend for a typical patient in CFD4870g study and shaded regions represent 5th−95th prediction intervals.

Le, K. N., Gibiansky, L., van Lookeren Campagne, M., Good, J., Davancaze, T., Loyet, K. M.,... & Jin, J. Y. (2015). Population pharmacokinetics and pharmacodynamics of lampalizumab administered intravitreally to patients with geographic atrophy. CPT: pharmacometrics & systems pharmacology, 4(10), 595-604.

Figure 2 Systemic PK.

Systemic PK. (A) Simulated serum concentration time course of total lampalizumab (solid red line), free lampalizumab (dashed black line), total CFD (solid blue line), free CFD (solid green line), and the total lampalizumab-CFD complex (dotted magenta line) following ITV administration (1 and 10 mg/eye). (B) The lampalizumab fraction of the total dose that is cleared by linear clearance (red) and TMDD (blue) as a function of the ITV dose. The fractions of the drug eliminated by target-mediated clearance (TMCL) and linear clearance (CL) are defined as total drug elimination through binding to the CFD and through the first-order drug clearance mechanism, respectively, which is normalized by total drug elimination.

Govindan, S. V., Cardillo, T. M., Moon, S. J., Hansen, H. J., & Goldenberg, D. M. (2009). CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clinical Cancer Research, 15(19), 6052-6061.