Asmacure’s scientific approach of using nicotinic acetylcholine receptor agonists for the treatment of inflammatory diseases originated from the very early clinical observations that smokers have a lower incidence of several inflammatory diseases, including hypersensitivity pneumonitis, a pulmonary disease caused by an increased immune response to inhaled antigens. Having done extensive research on the pathology on this disease, Dr. Cormier and his team have demonstrated that activation of these receptors by nicotine had a marked inhibitory effect on lung inflammation in a mouse model of HP Because nicotine is addictive and therefore presents a very limited therapeutic potential, the researchers tested dimethylphenylpiperazinium (DMPP), one of the numerous nicotinic agonists from natural and synthetic sources available commercially which is not expected to cross the blood brain barrier and thus not expected to have addictive properties.

Simultaneously with the study on HP, the researchers discovered that nicotinic receptors were present on eosinophils and airway smooth muscle cells, two important components involved in the pathology of asthma. Asthma was then selected as the initial target for future drug development.
In order to generate new compounds for pharmaceutical development, a series of analogues were subsequently synthesized leading to the selection of ASM-024 as Asmacure’s lead compound.

Proof-of-concept studies were conducted with DMPP and different new analogues. These compounds blocked the transmigration of eosinophils in vitro, had ex vivo relaxant effects on airway smooth muscle cells from mice, dogs and humans and had anti-inflammatory and bronchoprotective effects in animal models of asthma.