BioWorld International Correspondent

LONDON - VASTox plc swooped down on the assets of bankrupt MNL Pharma Ltd., acquiring a 1,300 library of natural imino sugars, a preclinical portfolio led by a cancer treatment MNLP462a, and a carbohydrate chemistry laboratory, for £240,000 (US$467,647).

The investors have put £10 million into MNL since it was spun out of the Institute of Grassland and Environmental Research in Aberystwyth, Wales, in 1999, to commercialize the research of Robert Nash, a leading phytochemist.

VASTox specializes in in vivo screens based on transgenic zebrafish and drosophila. "Our view of the world is that natural compounds are the way forward," Steven Lee, CEO, told BioWorld International. "Combinatorial chemistry hasn't worked."

The problem with many natural products companies however, is that "all they have are broths - they don't know what's in them," said Lee. "We have had our eye on Rob Nash for some time because he has got grams to tens of grams, of all the compounds [in the library]. That is highly impressive."

Imino sugars are naturally occurring, orally available sugar analogues that stimulate the immune system, inhibit enzymes and prevent viral protein synthesis.

Oxford-based VASTox intends to run the 1,300 compounds against its screens and will use any relevant ones as the basis for synthetic chemistry. "We're not going out to grow plants, but these represent a real opportunity as they are all bioactive compounds," Lee said.

The lead product MNLP462a is an immunomodulator with a novel mode of action that stimulates the immune system without activating deleterious inflammatory responses. In preclinical studies it reduced tumor numbers and size.

Lee said it is "a peach of a compound," which has shown signs of working as an antiviral also. VASTox will be required to pay up to £1 million to MNL's creditors as the compound progresses through clinical trials.

Nash and 11 colleagues at the carbohydrate chemistry laboratory in Aberystwyth will continue to operate, and Lee said by providing services to third parties, he expects it to cover costs within a year.

VASTox's disenchantment with combinatorial chemistry is down to the bitter experience of its nonexecutive chairman Barry Price, and Chief Scientific Officer Dick Storer. Both were senior chemists at GlaxoSmithKline plc (called Glaxo then) in January 1995, when the pharma company put the technology on the map with the $500 million acquisition of combichem pioneer Affymax NV.

Lee said the problem - as the two men see it - is that combinatorial chemistry does not relate to targets. "Draw a line from the ground to the sky: If your target is on that line, you will have a hit. If it is one millimeter either side, you won't.

"Combinatorial chemistry can only get you higher and higher on the same line, and the hits you get bind with similar affinities, so you then have to devote significant resources to optimizing them," Lee said.

No Comments