West Coast Editor

With a plan to boost the efficacy of antibiotics against particularly deadly and resistant bacterial pathogens, Mpex Pharmaceuticals Inc. licensed rights to Trine Pharmaceuticals Inc.'s patents pertaining to efflux pump inhibitors (EPIs) for undisclosed terms.

"We think we're definitely a leader in the space now," said Bill Gerhart, president and CEO of San Diego-based Mpex, which is hoping to "leverage all the work that's been done."

Efflux pumps are transport proteins that push toxic substances out of cells, responding not only to "bad" bugs, but to antibiotic substrates as well - which means that inhibiting the pumps could make the germ killers work better.

Mpex's focus on antibacterials already has yielded MP-601,205, a bacterial EPI (not part of the Trine deal), for respiratory infections in patients with cystic fibrosis (CF) and ventilator-associated pneumonia. The compound is an aerosol formulation of an approved drug that functions as an EPI, Mpex found.

"In CF, Pseudomonas aeruginosa is principally what causes lung function to deteriorate, leading to death," Gerhart noted. Often used against it first is TOBI, the inhaled tobramycin solution from Emeryville, Calif.-based Chiron Corp. that sold $51 million in the second quarter.

"It works great the first time," Gerhart said, but then patients develop resistance and need to be hospitalized. Mpex hopes to make a drug that is not only more potent, but also gets around the resistance problem.

The company disclosed the filing of an investigational new drug application for MP-601,205 - which is on the brink of Phase Ib/IIa trials - at the same time as the deal with Mountain View, Calif.-based Trine, the successor to Microcide Pharmaceuticals Inc.

"Around the time we go into Phase II we would reveal what that [the active ingredient] is, but we have some additional intellectual property we want to file," Gerhart said.

The endpoint for the study, to begin in September, is to show that a dose projected to work likely is to be tolerated and safe in the broader CF population. Providing financial and administrative support is the Cystic Fibrosis Foundation, and the study will be conducted at the Adult Cystic Fibrosis Center at the University of California San Diego Medical Center.

If the Phase Ib trial comes off as planned, Mpex aims to begin a Phase II trial testing MP-601,205 in combination with ciprofloxacin to treat pulmonary exacerbations in CF patients.

Mpex's drug is similar to the blockbuster antibiotic Augmentin, a combination of amoxicillin and clavulanate potassium from London-based GlaxoSmithKline plc, which hit the market in 1987 and went off patent last year, except that MP-601,205 provides a different mechanism of resistance and targets hospital-based rather than community-based infections.

"We're principally focused on Gram-negative bacteria that are the most resistant, serious pathogens - fixing the hole" by providing a much-needed therapy, Gerhart said. The patent estate to which Mpex gained rights covers the discovery, development and use of EPIs to enhance antibiotics.

About nine years ago, Microcide entered a $10 million deal with Tokyo-based Daiichi Pharmaceutical Co. Ltd. for EPIs against bacterial infections. (See BioWorld Today, Nov. 20, 1995.)

"That was a five-year collaboration where they completely validated the biological target and got animal efficacy," Gerhart said, but toxicity issues led the work to stop, and the deal was dissolved.

"We thought there were pretty compelling reasons based on new information to take another run at it," he told BioWorld Today, adding that Mpex has "significantly advanced the science, but benefited from the work that had been done."

Microcide in 2001 merged with The Althexis Company Inc., of Waltham, Mass., to become Essential Therapeutics Inc., which went bankrupt last year and emerged from that process as Trine.

"Daiichi still has some rights [to EPIs] because some of those patents were joint patents, but I don't know what they're doing with them," if anything, Gerhart said.