Northern Antibiotics looking to partner novel and safer polymyxins

Licensing opportunity

The emergence of multidrug-resistant Gram-negative bacteria has necessitated the use of polymyxins as the agents of last resort despite their known kidney, or nephrotoxicity. Now Northern Antibiotics Ltd, a Finnish biotech company, has developed novel polymyxin derivatives that in early preclinical studies show signs of reduced nephrotoxicity, which it is now looking to partner.

The derivatives contain three positive charges only, while existing products, polymyxin B and colistin have five. The new compounds bind to rat kidney cells at an affinity which is only one-fifth to one-seventh of that for polymyxin B.

In vivo rat studies also show remarkable differences in parameters that are considered to indicate early kidney damage, such as serum urea nitrogen, albuminuria and cylindrouria.

The derivatives fall in to two groups that differ in their mode of action. The lead compound of the first group, NAB 7061, sensitises enteric bacteria to other antibiotics, while NAB 739, the lead compound of the second series, acts directly against enteric bacteria.

“The efficacy of both lead compounds has been verified using an experimental E. coli peritonitis model in mice, and we are now talking to potential partners to further develop and eventually commercialise these two lines of novel compounds,” says Helsinki University Hospital professor Martti Vaara, CEO and co-founder of Northern Antibiotics Ltd.

“The need for well-tolerated antibiotics that are active against multidrug-resistant Gram-negative bacteria is urgent. Enteric bacteria are responsible for more than 80 percent of all the hospital infections caused by Gram-negative bacteria, and now they are rapidly becoming resistant to most antibiotics that are currently used to treat them.”