Table 3.

Novel protease therapies in clinical and preclinical development

Protease	Developer	Technology description	Disease indication	Development stage
Liprotamase, protease from the fungus Aspergillus melleus	Eli Lilly	A component of Trizytek™ (digestive enzymes: lipase, protease and amylase mixture)	Cystic fibrosis with exocrine pancreatic insufficiency	Phase III/NDA (New Drug Application)
Microplasmin	ThromboGenics NV	Recombinant microplasmin injected into the vitreous humour of the eye	Vitreomacular adhesion	Phase III
Glutamine-specific cysteine protease (EP-B2) and a proline-specific prolylendopeptidase (PEP), ALV003	Alvine Phamraceuticals	Recombinant proteases to digest gluten	Coeliac disease	Phase II
Microplasmin	ThromboGenics NV	Recombinant microplasmin	Acute peripheral arterial occlusion, deep vein thrombosis	Phase II
Plasmin	Talecris Biotherapeutics	Plasma-derived plasmin	Peripheral arterial occlusion	Phase I
Recombinant plasmin	Talecris Biotherapeutics	Recombinant plasmin	Peripheral arterial occlusion	Preclinical
Recombinant plasmin (BLX-155)	Biolex	Recombinant plasmin	Acute peripheral arterial disease, deep vein thrombosis and haemodialysis	Preclinical
Recombinant human lysosomal protease, HTI-501	Halozyme	Recombinant FVIIa variant, developed with gene shuffling technology	Medical and cosmetic dermatological applications	Preclinical
Kallikrein	Wanxing Pharmaceutical	Recombinant human kallikrein-1	Thrombosis, peripheral vascular disease, cerebrovascular ischaemia	Preclinical
Calpain 3	Généthon	Gene therapy; adenoviral vectors containing caplain 3	Replacement therapy, calpainopathy (a limbgirdle muscular dystophy)	Discovery
Penzyme	Zymetech	Proteases that digest outer layers of skin	Psoriasis, eczema and dermatitis, cosmetic dermatological use	Marketed for topical use, not FDA-approved