Cancer immunotherapy is one of the most important recent scientific breakthroughs. However, many patients remain unresponsive to current immunotherapies. New mechanisms that induce tumor immune-evasion need to be explored to develop more efficacious combination therapies.
Prostaglandin E2 (PGE2) drives cellular inflammation, proliferation, autoimmunity and cancer immune-evasion, signaling through several receptors. The EP2 and EP4 receptors are involved in immune suppression and metastasis, with EP4 selective antagonists currently in clinical trials.
MBF-362 is a potent and selective EP2/EP4 dual antagonist arising from structure-based design. EP2 and EP4 work in tandem through cyclic AMP cell signalling. Dual antagonism is positioned to effectively block this pathway, eliminating the possibility of compensatory mechanisms after single receptor antagonism.
The compound has demonstrated efficacy in solid tumor models, showing synergy in combination with anti-PD-L1 antibodies.
MBF-362 has shown excellent safety and tolerability in IND-enabling studies. It is currently completing preclinical formulation, prior to evaluation in oncology patients in a phase Ib trial.
The molecule is protected by IP, wholly owned by Medibiofarma.