By Randall Osborne

West Coast Editor

Coley Pharmaceutical Group Inc.¿s CpG immune modulators netted the firm its largest collaboration, an agreement with Aventis Pharma AG for asthma and allergic rhinitis that is ¿far bigger¿ than last year¿s potential $72 million infectious-disease deal with GlaxoSmithKline plc, said Robert Bratzler, Coley¿s president and CEO.

Aventis, of Frankfurt, Germany, gains a worldwide license to Wellesley, Mass.-based Coley¿s lead molecule, CpG 9328, and up to three others. Privately held Coley gets milestone payments, and double-digit royalties on any Aventis product sales.

Along with CpG 9328, Coley has a compound in preclinical investigation that is covered by the Aventis agreement, Bratzler said. The two others included in the deal have yet to be discovered.

CpGs work by modifying the immune system at the top of the inflammatory cascade and redirecting hypersensitive reactions into more normal responses, by suppressing allergic (Th2-type) immune responses and inducing more normal (Th1-type) responses.

¿This is an altogether new approach for the treatment of pulmonary disease, which is to go to the top of the immune system cascade, right where the immune system is trying to decide how it¿s going to react,¿ Bratzler said. ¿It works very well in animals, and this was a good part of Aventis¿ interest.¿

He called the deal ¿a first-in-class drug opportunity. In terms of allergy and asthma, [the field] is crowded, but in terms of immune modulation, there aren¿t any other companies that do this,¿ Bratzler told BioWorld Today.

¿From the time that we discover these compounds until we get them to the clinic has been as short as 18 months,¿ he added, crediting the firm¿s Human Cell Screening technology. ¿That was [another] of the things attractive to Aventis. We do the screening on human cells, so it¿s not a prolonged preclinical [process]. We know pretty much which compounds will excel in allergy and asthma, and which are perhaps destined for other disease indications.¿

Aventis already markets the popular allergy drug Allegra (fexofenadine), Bratzler noted.

¿You can imagine they would want to have multiple entries,¿ he said. ¿If you could work upstream [in the inflammatory cascade], this would be ideal.¿

Coley is primarily focused on cancer. Its lead product, ProMune, is in Phase I/II clinical trials for several cancer indications. With nine Phase I/II clinical trials ongoing, Coley also has a program in infectious diseases. The deal with GlaxoSmithKline plc gave the London-based firm a worldwide co-exclusive license to cytosine-quanine dinucleotide DNA-based compounds, including CpG 7909, Coley¿s lead immune stimulant, for use in certain therapeutic and prophylactic vaccines for infectious diseases. (See BioWorld Today, Jan. 19, 2000.)