Overview
FXT's research is based upon a strategy that exploits functional screening to develop new classes of drugs with novel mechanisms of action.
Rapid and efficient identification of proteins and peptides with therapeutic potential by functional screening is coupled with proprietary methods of generating small molecule pharmaceuticals that mimic the function of these lead proteins and peptides.
To date this strategy has led to the discovery of a novel anti-inflammatory pathway, which plays an important role in the normal resolution of inflammation and is perturbed in chronic inflammatory conditions including asthma and rheumatoid arthritis. This pathway is acting through the type-2 somatostatin receptor (sstr2), which has previously been associated with significant anti-inflammatory activity in various clinical and non-clinical studies using somatostatin and its analogues (see selected publications on the anti-inflammatory activity of somatostatins in the Press Room section). The major limitation for the clinical use of these compounds in inflammation however has been their potent endocrine effects.
FXT has discovered a second class of natural ligands at sstr2, which offer a solution to this problem and involve various mechanisms, including the sequential action of arginase-2 and proteases (such as thrombin) on peptide substrates, to generate a novel post-translational modification of a C-terminal lactam. These C-terminal lactam peptides (CTLPs) are specific ligands at sstr2 and mediate anti-inflammatory effects through sstr2, but without agonist activity on endocrine markers at the dose levels required for anti-inflammatory activity. The importance of this pathway is revealed by genetic studies conducted by FXT, which showed that variation at the sstr2 locus is associated with chronic inflammatory conditions, and also by studies of IGF-1 levels which are depressed during chronic inflammation due to the low levels of CTLPs that normally compete with somatostatin binding at sstr2.
This knowledge allowed the development of a novel class of molecules (somatotaxins) that target the CTLP pathway, with the most advanced of these molecules (FX125L) ready to start Phase II studies. FXT’s other proprietary technology, the G-protein coupled receptors Agonist-Enriched Libraries (GAEL) is an enabling platform technology for functional screening.