New biological entity vs. new chemical entity

Two different drug discovery strategies are considered for the development of novel immuno-oncology treatments targeting GPCRs. On one side, are the drugs that will interfere with the recruitment of immunosuppressive cells, and on the other side are the drugs blocking metabolic checkpoints. For the first category, antibody is the drug paradigm of choice since chemoattraction is often produced with a cytokine gradient pointing toward the tumor. Antibodies are well positioned to compete with a cytokine-GPCR interaction in comparison to small molecule. On the contrary, for the second category, new chemical entity ( NCE ) based on small molecule drugs is the most appropriate paradigm since metabolic checkpoints are often made of smaller nature than cytokines.

 

New chemical entity drug discovery capacity at Domain Therapeutics

Over the past decades, Domain Therapeutics has accumulated a solid track record in SME drug discovery illustrated by multiple programs reaching the clinic (Foliglurax mGluR4 PAM for Parkinson’s disease, M1069 adenosine antagonist in collaboration with Merck KGgA for immuno-oncology) or the pre-IND studies ( DT-9081 EP4R antagonist for immuno-oncology). This expertise was reinforced with the acquisition in 2020 of Prestwick Chemical, a company founded by Pr Camille G. Wermuth, with great expertise in medicinal chemistry. Such acquisition enabled Domain Therapeutics to double the size of its chemistry department In addition, Domain Therapeutics possesses its proprietary SME chemical library used in high throughput screening efforts to initiate drug discovery programs, and its own technology platform bioSens-All®️ dedicated to the characterization of multiple signalling pathways downstream of a GPCR activation. Thanks to this, Domain Therapeutics is able to launch multiple small molecule drug discovery programs with the objective to bring to the clinic small molecule drugs as promising immunotherapies.

 

bioSens-All®️ platform

In 2013 and 2016, Domain Therapeutics was granted with two exclusive and worldwide licences on BRET-based technology named bioSens-All®️ from the University of Montréal and McGill University. This technology, developed and validated by Pr Michel Bouvier and colleagues from Montréal Universities, is specifically designed to profile the signalling signature of GPCR ligands or drugs investigating the downstream pathways. It is particularly suitable for the identification and development of biased ligands, and for the identification of pathways engaged in specific environment like that of the tumors. Domain Therapeutics takes advantage of this unique technology to conduct its drug discovery SME and NBE programs.