NEWCASTLE UPON TYNE, U.K.—Looking to tap into one of the most biologically diverse regions on the planet for next-generation drugs, e-Therapeutics recently announced it had formed discovery partnerships with two Brazilian groups—Grupo TCI and CURA, a pharmaceutical consortium backed by the Brazilian government.
"Evolution has been tremendously good at finding innovative ways to poison or otherwise affect neighbors, so it was natural that we would start looking seriously again at natural biochemical diversity," says e-Therapeutics CSO Prof. Malcolm Young. From his perspective, the general move from natural product-based research to combinatorial chemistry as a source of chemical diversity hasn't been particularly successful.
"We were looking for two things: real ambition in relation to world markets, and extensive natural product libraries," Young explains. "TCI and CURA are well placed to exploit both those things from Brazil."
According to CURA president Romulo Queiroz, the groups expect to spend about $30 million, split evenly, to establish the research facilities necessary to pursue their objectives, although they are still developing project financing. Unfortunately, he says, existing Brazilian facilities need significant investments to become world-class and globally competitive, and the monies have not been available in recent years.
Another key for the collaboration is the ability to access genetic assets that are only available to domestic companies under Brazilian law. Thus, explains Queiroz, the Brazilian company will hold the necessary permits for biodiversity access, bioprospecting and technological development.
The project will largely rely on the screening of newly discovered compounds using e-Therapeutics' computational systems biology platform, developed by Young at Newcastle University, where he is Pro-Vice-Chancellor.
As Young explains it, researchers start with two large data resources: one based on macromolecular interactions; the other on interactions between small molecules and macromolecules (i.e., chemogenomics). Thus, for a given new molecule, they start with its structure and any known affinities to derive an interaction spectrum. They then perform an impact analysis across ~40 human cell-types and ~100 pathogens to generate a predicted indication and risk profile.
The researchers can also start at the other end of the process, with a disease state, from which they derive a desired interaction spectrum. They then map this spectrum to matching compounds and "de-risk" the candidates for factors such as efficacy, toxicity, side-effects and drug interactions.
"On a recent antibiotic sweep across 97 pathogens using only our own data resources and analyses, we recovered 103 known antibiotics, including all the known antibiotic classes, together with novel antibiotic indications for other molecules, which have since panned out very well in the laboratory," Young says.