ß-lactamase inhibitors

ß-lactamase inhibitors (BLIs) are compounds that protect resistance susceptible ß-lactam antibiotics from deactivation by infectious bacteria. As a combination of two compounds, BLIs + ß-lactam antibiotics have been exceptionally successful over the last twenty years.  Augmentin^® (GlaxoSmithKline), which is a mixture of clavulanic acid (the BLI) and amoxicillin, launched in 1981, had sales in 2001 of $2.05 billion.  Tazocin^® (Wyeth), a mixture of tazobactam and piperacillin (the BLI) had sales of $427 million in 2001.  These first generation ß-lactamase inhibitors are narrow spectrum. They are very effective against the older class A enzymes but poor against the increasingly prevalent class C enzymes produced by emerging bacterial strains. Amura have exclusive commercial and intellectual property rights to a new generation of ß-lactamase inhibitor, the oxapenems, that have broad-spectrum ß-lactamase inhibitory activity as well as intrinsic anti-bacterial activity. As such they fulfil an urgent and increasingly important need in the fight against emerging resistant bacteria.

General information on ß-lactamases: link here

General information on antibiotics: link here 

General information on clavulanic acid: link here

AM-112 is a lead candidate oxapenem  ß-lactamase inhibitor (BLI) that exhibits substantially improved chemical stability within this otherwise labile class of compounds. AM-112 is an ideal combination partner for resistance susceptible ß-lactam antibiotics including: penicillins, cephalosporins and carbapenems to be used in first-line i.v. treatments for broad-spectrum hospital-acquired bacterial infections. The comprehensive pre-clinical package compiled for AM-112 has made significant progress over the last 2 years and now includes extensive in vitro and in vivo microbiology, toxicology, a scalable chemical synthesis, and establishment of broad ranging granted intellectual property rights.

Notable highlights are detailed here;  

AM-112 represents a distinct class of ß-lactamase inhibitor.  It shows synergistic effects when partnered with ß-lactam drugs such as cephalosporins, penicillins and carbapenems. Whilst effective against Class A ß-lactamases, Augmentin^®, Unasyn^® and Tazocin^® have not been as successful against Class C, D or extended spectrum ß-lactamases (ESBLs).  AM-112 overcomes or markedly diminishs the resistance of many pathological bacteria through its strong activity against Class C ß-lactamases, but retains significant activity against Class A, Class D and ESBLs making it a very potent broad spectrum combination candidate for first-line therapy in nosocomial infections.

Susceptibility (MICs) to the ß-lactam ceftazidime; a ceftazidime + clavulanic acid combination; a ceftazidime + AM-112 combination. A similarly impressive expansion of susceptible isolates is also seen with other ß-lactams in combination with AM-112.

The AM-112 programme is available as a stand alone investment opportunity, or for licensing or for partnership towards progression and commercialisation of next generation antibiotics.