Asthma/Allergy

Target: CRTH2
Status: Discovery

7TM Pharma develops a CRTH2 antagonist as novel non-steroidal orally available drug for inflammatory/respiratory diseases; the compound is in late lead optimization and was a model case in the application of our proprietary drug discovery platform Site Directed Drug Discovery®.

The Target

The CRTH2 receptor (chemoattractant receptor expressed on T Helper type 2 cells) has recently been identified as the molecular target for the proinflammatory lipid mediator prostaglandin D2 (PGD2)1. PGD2 is the major prostanoid released by activated mast cells and is supposed to play a central role as a mediator in allergic diseases. The fact that PGD2 is considered as a key mediator in allergic asthma/atopic diseases together with the identification of CRTH2 as the molecular target mediating many of these proinflammatory effects implicates CRTH2 as a promising and novel target for treatment of asthma and atopic/allergic diseases in general.

The Indication

Allergic diseases are a major healthcare burden with an increasing prevalence worldwide. Allergic rhinitis is the most common allergic disease, associated with the development of other diseases like asthma, rhino-sinusitis, or allergic conjunctivitis. Other allergy diseases include Atopic dermatitis and Allergic conjunctivitis. In the U.S. alone, some 60 million people suffer from some form of allergic rhinitis, worldwide the number is 150 million. The total worldwide market for drugs treating allergic rhinitis is estimated with USD 2.9 billion. According to the WHO, between 100 and 150 million people around the globe suffer from asthma; worldwide, deaths from this condition have reached over 180,000 annually; incidence rates worldwide are on average rising by 50% every decade. The whole market for asthma/atopic disease is expected to increase by 35% to over USD 18 billion by 2011. (2)

Due to the chronic nature of allergic and asthmatic diseases, the need for drugs that effectively control these diseases and delay progression is increasing. Early detection and intervention has proven important in reducing long term morbidity. However, for asthma in particular, therapy has remained essentially unchanged over the past 30 years, with inhaled bronchodilators and anti-inflammatory corticosteroids still representing the main treatments. Leukotriene receptor antagonists have recently provided opportunities for oral treatment, but have drawbacks both in terms of efficacy as well as safety. There is therefore a clear need for developing novel, efficacious and safe non-steroidal oral anti-inflammatory drugs to allow for broader and earlier treatment, especially for children, where the use of steroidal treatments is a general concern.

(1) Hirai et al., J Exp