Metabolic teams with BresaGen to produce anti-obesity compound

Melbourne biotechnology company Metabolic Pharmaceuticals has engaged Adelaide biotech BresaGen to develop a scaleable production system for its promising anti-obesity compound AOD9604.

Metabolic's CEO, Dr Chris Belyea, said BresaGen would develop an expression system employing E. coli bacteria that could eventually be scaled up to produce the AOD9604 molecule, a peptide of 16 amino acids, derived from the human growth hormone (hGH) protein molecule.

Belyea said BresaGen possessed the technology and expertise to develop an E. coli expression system that could eventually be scaled up to produce the peptide in multi-tonne quantities annually .

International life sciences company Monsanto has already achieved multi-tonne commercial production of bovine growth hormone -- also known as bovine somatotrophin, used to increase milk production in dairy cattle in the US.

Because E. coli is generally suitable only for synthesising larger proteins -- it tends to degrade small peptides during synthesis -- Belyea said BresaGen's protEcol Services divison would have to embed the Metabolic peptide within a larger protein, then cleave the resulting molecule to yield the active, 16-amino acid molecule.

The production and purification process that BresaGen develops is likely to be licensed eventually to the pharmaceutical company that Metabolic selects to produce the anti-obesity drug.'

"We're talking to several big pharmas, but our approach has always been that we'll get the most value from a partnership after we prove the drug works in human trials," Belyea said.

The prototype drug emerged from of research by Monash University biochemist Prof Frank Ng into the functional properties of human growth hormone (hGH).

HGH is, in effect, three hormones rolled into one -- it consists of three functional domains, that have very different effects on target tissues.

One domain stimulates lactation in mammals -- the application for which bovine somatropin is used in US dairy cattle herds. Another modulates the response of fat-storage cells to glucose; Metabolic is developing this domain as a potential therapy for insulin-resistant diabetes.

The third -- Metabolic's AOD9604 molecule -- is involved in breaking down cellular fat stores, inhibiting the synthesis of new fat, and promoting muscle growth -- it mimics the effect of exercise.

The molecule is the furthest advanced in the company's development pipeline.

The compound has already been shown to cause rapid weight reduction in genetically obese laboratory rodents, and was well tolerated in a Phase IIa single-dose trial in human volunteers earlier this year.