Immuno-oncology (IO) represents the major breakthrough for cancer treatment of the last decades. Unlike traditional therapies that target directly cancer cells, this novel strategy consists in mobilizing the patient’s immune system to eliminate cancer cells. However, despite multiple recent successes, a significant percentage of the patient population are still resistant to such therapies. Therefore new mechanisms of action need to be exploited in order to deliver novel drugs that will ultimately increase the rate of responders to IO treatments.
DT-9081 is a drug candidate targeting prostaglandin receptor 4 (EP4R). It has the potential of best-in-class treatment in immuno-oncology.
EP4R antagonist (DT-9081)
Multiple cancers are using GPCRs localized on a variety of immune cells to shut down the immune response by over-producing their corresponding endogenous ligands. It is the case for adenosine and the A2A receptors, but also for prostaglandin E2 (PGE2), over-produced in COX2 overexpressing tumors, and activating the prostaglandin receptor 4 (EP4R). Antagonizing EP4R is therefore a novel therapeutic approach to restore cancer recognition by the immune system and combat its progression.
We discovered a new chemical series of EP4R antagonists. In 2019, DT-9081 was nominated as a development candidate ready to enter regulatory studies. We have also developed a biomarker in the rodent, transferrable to the clinic, that showed superiority of DT-9081 over compounds from the competition.