Domantis find expected to benefit Abbott

UK antibody therapeutics developer Domantis has pulled a double-headed rabbit out of the hat for its client, the big European pharma Abbott Laboratories.

Abbott contracted Domantis in 2002 to develop a second-generation successor to its US$6 billion-a-year anti-inflammatory therapy, Humira a monoclonal antibody targeting the key inflammation mediator TNF-alpha.

Domantis, which is 36.1 per cent owned by Sydney biopharma Peptech (ASX:PTD), said it had achieved a milestone with its proprietary domain antibody (dAb) technology, by developing a dAb that simultaneously binds two targets involved in inflammatory disease.

Domantis has not revealed the targets, but executive vice-president and CSO, Ian Tomlinson, said drugs based on double-acting dAbs could prove more effective, cause fewer side-effects, and address a broader patient population compared to traditional treatments.

Tomlinson said the new dual-targeting dAb had the potential to address a "significant, unmet medical need". Abbot is paying Domantis licence fees, development milestones and royalties on dAb-based products.

He said many human illnesses are multi-factorial, and involve a number of targets. Manufacturing and purification problems had hampered previous efforts to produce antibodies that could bind multiple targets.

The company can manufacture fully humanised dAbs with existing techniques, and Tomlinson said they could be used to treat a broad range of disorders, including autoimmune disorders and cancers.

Domantis has a dozen of its therapeutic programs, and six partner programs, some of which are in preclinical development. A third involve creating dual-targeting antibodies.

Peptech is developing its own Domantis-designed anti-inflammatory dAb as a therapy for rheumatoid arthritis and other inflammatory disorders; it plans to seek a large pharma partner to commercialise the drug, and Abbott's dAb could be a rival.

But Peptech chairman Mel Bridges said the Abbott molecule would not be a competitor for the Peptech product if both reach the market -- and in any case, the Abbott molecule is likely to be longer in the clinical trials process because it will be "cutting new turf" with the dual-function dAb. Domantis is developing other dAbs for Peptech, but Bridges said they are not dual-function. "We think there are plenty of commercial opportunities with single-target dAbs, he said.

CSIRO designer-antibody specialist Dr Peter Hudson said bi-specific domain antibodies were an evolutionary step from bi-specific monoclonal antibodies.

He said the Abbott molecule was likely to comprise two dAbs, with different specificities, linked back-to-back with a peptide bond, rather than via a chemical bond. Each dAb consists of the pruned-down, active domain of a normal antibody. "There is a real opportunity to use this sort of molecule to recruit cytotoxic T-cells to attack cancers, or to use them in a range of diagnostic applications involving more than one target," Hudson said.