Osteoporosis current status

Amura has developed low nanomolar inhibitors of cathepsin K with excellent selectivity (greater than a hundred fold) versus closely related homologs.  These AMcore™ based candidates exhibit high oral exposure, low clearance in vivo and cross-species inhibitory activity, thereby facilitating efficacy studies in disease related animal models.  A study, designed to evaluate a series of orally bioavailable inhbitors in an ovarectomized rat model, concluded that all test compounds showed a dose dependent capacity to decrease osteoclast activity (i.e sCTxI) and increase bone formation (i.e. osteocalcin).  As a result, turnover index (sCTxI/osteocalcin) was significantly decreased by all test compounds.  Coupled to this, an acute pharmacokinetic and pharmacodynamic (PK/PD) study in non-human primates demonstrated that oral administration of compounds resulted in the sustained and potent reduction of serum bone turnover biomarkers.  The compounds were well tolerated and showed no adverse effects.  The results further support progression of these compounds towards the clinic, offering the potential for new osteoporosis treatments.

A long term goal of osteoporosis research has been to find agents that can deliver beneficial effects on both bone degradation and bone growth.  Amura has now demonstrated that this is achievable in animal models and the high quality molecules from Amura enable rapid progression to clinical trials for a similar demonstration in humans.

Amura has licensing opportunities for its AMcore™-based programmes.