Arriva has developed two other protease inhibitors that are currently in the development and preclinical phase.
Ilomastat: Ilomastat is a potent, broad spectrum inhibitor of matrix metalloproteases and has shown to be active in a number of animal model systems of inflammation. Arriva has shown that Ilomastat can reduce macrophage levels and reduce airway enlargement by >90% in the smoking mouse model1. In ex vivo human studies, Ilomastat has also been shown to inhibit matrix metalloproteases associated with chronic childhood middle ear infection (otitis media)2.
SLAPI: SLAPI is a fusion protein that combines Secretory Leukocyte Protease Inhibitor (SLPI) and rAAT, and can be produced at high levels in yeast. It inhibits neutrophil elastase, chymase, cathepsin G and kallikrein through the rAAT portion and inhibits neutrophil elastase and tryptase through SLPI. SLAPI has demonstrated activity in ex vivo studies with smokers with COPD.
Reference:
1. P. Pemberton et al., COPD; Journal of Chronic Obstructive Pulmonary Disease, 3:303-310 (2005).
2. P. Antonelli et al., The Laryngoscope, 115:651-654 (2005).
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