Domantis lung study nets 'exciting' results

UK human domain-antibody (dAb) developer Domantis has reported spectacular success in trial of an inhaled anti-inflammatory dAB in an in vivo model of chronic obstructive pulmonary disorder (COPD).

Domantis is 36.1 per cent owned by Sydney peptide pharma Peptech (ASX:PTD). It developed the anti-inflammatory dAb in collaboration with privately owned UK pharma Argenta Discovery, which has developed a novel system for evaluating drug leads for lung disease.

Peptech has its own Domantis-developed anti-inflammatory dAb in preclinical trials; targets the inflammatory cytokine TNF-alpha -- Domantis and Argenta are keeping their new dAb's pro-inflammatory target a commercial secret.

Peptech executive chairman Mel Bridges today described the result as "exciting", and confirmed the target was not Peptech's own patented target, the TNF-alpha receptor.

Bridges said Peptech had been watching the trial with interest, because the anti-TNF-alpha dAb is also a candidate therapy for asthma -- although Domantis and Peptech have not yet experimented with this application, Bridges said it was an "interesting" prospect.

"The exciting thing is not just the positive outcome for COPD, but that the trial confirms that dABs can be delivered by the inhalant route. Arguably, that's more exciting than the COPD result," he said.

"We already know we can deliver dABs by the subcutaneous and intramuscular route. The next major step would be oral delivery."

COPD is a catch-all medical term for a group of closely related lung disorders that includes emphysema, chronic asthma and chronic bronchitis. Frequent respiratory infections in early childhood predispose individuals to COPD later in life. The World Health Organisation estimates that COPD killed 2.7 million people around the world in 2000 -- most were heavy smokers.

There is no effective anti-inflammatory drug for the disorder and no therapy that effectively slows the irreversible decline in lung function. Anti-inflammatory therapy with steroids reduces lung inflammation only one in five patients, and can have serious side-effects.

COPD is the already the fourth leading cause of premature death worldwide, and with the aging of a huge cohort of addicted Asian smokers, is predicted to rise to third as a cause of premature death, and fifth as a cause of chronic disability by 2020.

Minimal side-effects

In a joint statement, Argenta's director of R&D, Dr Mary Fitzgerald, said the companies believe the new dAB can become the anti-inflammatory of choice for COPD patients. By reducing lung inflammation, the antibody is expected to reduce the severity of symptoms, and slow -- or even halt -- the decline in lung function.

An effective anti-inflammatory agent could bring relief to millions of patients, and in marked contrast to other drugs currently in development, promises to have minimal side-effects -- because of its tiny size, the dAb is rapidly cleared from the bloodstream, after doing its work in the lungs.

Domantis owns exclusive rights to the technology for producing dAbs, which consist of conventional human antibodies pruned down to their essential, antigen-recognising domains.

Domantis executive VP and CSO Dr Ian Tomlinson said the study further demonstrated the unique product potential for human dAbs. "It shows that dAbs can be delivered by inhalation directly to targets in the lung to treat pulmonary disease, something that cannot be achieved effectively with conventional human antibodies," Tomlinson said.