Pegulicianine

Pegulicianine is a prodrug that is optically inactive when intact and produces a fluorescent signal after its peptide chain is cleaved by cathepsins and matrix metalloproteases (MMPs). The levels of these enzymes are higher in and around tumor and tumor-associated cells than normal cells.

This enzymatic cleavage results in “fragment 2” and “fragment 3”, which are optically active metabolites that emit fluorescence, as well as “fragment 1” containing the fluorescence quencher that keeps the intact molecule optically inactive. “Fragment 2” and “fragment 3” absorb light in the visible light region with a peak absorption at 650 nm and fluoresce with a peak emission at 675 nm.

The relationships between the plasma concentrations of the optically active metabolites and the time course of pharmacodynamic response have not been fully characterized.

Elimination

Metabolism

Pegulicianine is cleaved by cathepsins and matrix metalloproteases to the active metabolites “fragment 2” and “fragment 3.” Pegulicianine undergoes minimal hepatic metabolism in vitro.

Excretion

Pegulicianine excretion pathway in humans is unknown. Observed blue/green discoloration of urine (chromaturia) in subjects receiving pegulicianine suggests that pegulicianine and/or its metabolites may be excreted renally.

Specific Populations

Patients with Renal Impairment

Mild renal impairment (RI) does not appear to have a clinically meaningful effect on the pharmacokinetics, safety, and efficacy of pegulicianine and fragment 3; fragment 2 data are not available. The effect of moderate or severe RI on the pharmacokinetics, safety, and efficacy of pegulicianine, fragment 2, and fragment 3 has not been evaluated.