Aggregate technologies: GPCR-Signalling, trans-membrane biophysics, and molecular design to address unmet need in inflammatory diseases

Diseases of interest

A number of underserved inflammatory diseases make up the focal interest of our company. Namely pulmonary fibrosis, eosinophilic oesophagitis (EoE), and primary sclerosing cholangitis (PSC). Find Therapeutics is focused on these inflammatory diseases which present a great unmet medical need.

GPCR-Signalling

Find Therapeutics has access to bioSensAll^TM, a proprietary technology to Domain Therapeutics, revolving around the spatiotemporal monitoring of receptor proximal events directly linked to GPCR activation. The bioSensAll^TM platform includes a unique set of biosensors spanning different effectors and offers a pluridimensional vision of GPCR signaling signature. Its unique combination of adaptability, HTS compatibility and real-time kinetics capabilities help generate the quality of data required to enhance drug discovery in the field of GPCRs. To date, the bioSensAll^TM platform includes biosensors for the activation of 16 distinct heterotrimeric G-proteins, as well as sensors for the engagement of ß-arrestin 1 and 2.

GPCRs represent one of the most important druggable target class, yet their full potential remains underexploited due to poor understanding of their cellular signalling. Current methodologies used for GPCR-ligand profiling involve the measurement of second messenger production (i.e., calcium, inositol trisphosphate, or cAMP). Such readouts are relatively distal to the GPCR and rely on biological responses that can be modulated by various (often cross-talking) receptor downstream signaling pathways. Consequently, second messenger levels alone are not directly indicative of a ligand's activity or efficacy and their use for ligand profiling may thus lead to erroneous conclusions.

Biophysical approaches

A greater number of GPCR crystal structures are being published and made accessible. This provides a clearer understanding of monomeric and multimeric functional interactions which are capital to proper ligand-receptor signalling. The combination of structural information, computational modeling, and a better understanding of dynamic shifts of such protein systems, provides an additional insight in designing high affinity and high efficacy ligands, and drugs.

Molecular design

Today, drug discovery efforts use molecular design in all its steps towards effective medicines. This is applied from the molecular level to address high target affinity, efficacy and metabolic stability. This is an integral part of Find Therapeutics platform.