Valanafusp alfa

Valanafusp alfa (AGT-181) is a chimeric monoclonal antibody that fuses human α-L-iduronidase (IDUA) and targets the human insulin receptor (HIR). Valanafusp alfa has brain penetrating properties, making it useful for research on mucopolysaccharidosis type I (MPS I).

Valanafusp alfa (HIRMAb-IDUA) binds to the HIR extracellular domain (ECD) with an EC50 of 0.93±0.07 nM[2].Valanafusp alfa (HIRMAb-IDUA) (0.3 μg/mL; 48 h) reduces glycosoaminoglycan accumulation in Hurler fibroblasts by 70% as compared to healt fibroblasts[2].

Chronic dosing of Valanafusp alfa (AGT-181) (0.2-20 mg/kg; IV) has an excellent safety profile at all doses with no clinical, histologic, or laboratory findings, and no effect on glycemic control in plasma or cerebrospinal fluid[1].Valanafusp alfa (AGT-181) (0.2-20 mg/kg; IV) is stable, and shows rapid clearance and the high systemic volume of distribution in Rhesus monkeys[1].

References:
[1]. Boado RJ, et al. AGT-181: expression in CHO cells and pharmacokinetics, safety, and plasma iduronidase enzyme activity in Rhesus monkeys. J Biotechnol. 2009 Oct 26;144(2):135-41.
[2]. Boado RJ, et al. Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier. Biotechnol Bioeng. 2008 Feb 1;99(2):475-84.