IDO Inhibitors-Pipeline Insights

• Indoleamine-2,3-dioxygenase (IDO) is one of the immune checkpoints involved in tumor immune response. It is an intracellular heme-containing enzyme that makes up the first and rate-limiting step of tryptophan degradation along with the kynurenine pathway.
• By inhibiting IDO, researchers hope to revive immune system responses so that tumor cells are more easily identified and destroyed.
• In addition, to revamping the approach to treat advanced melanoma, the success of IDO inhibitors in the market will also help metamorphose the treatment of NSCLC, TNBC, and bladder cancer with the existing therapies.
• IDO is a prototypical integrative modifier that bridges inflammation, vascularization, and immune escape to license primary and metastatic tumor outgrowth.
• The global IDO inhibitors market is yet to gain its first approval for treatment of solid tumors. Majority of these drug molecules are still in pre-clinical stage, a fragment of them being in Phase II.
• Many molecules in phase 3 have raised the anxiety and hope to achieve positive results after the failure of trials from major pharma companies like BMS, Merck.
• IO Biotech is developing 2 IDO inhibitors that are in phase 2 stage of development. Navoximod of Newlink Genetics is in the Phase 1 stage of development. Many molecules from Emcure Pharma, Huya Bioscience, InventisBio are pre-clinically tested for its efficacy.
• The IDO inhibitors are being developed for the treatment of solid tumors such as skin and lung cancer and revealed that during the pre-clinical studies, the IDO inhibitor already exhibited potent cellular activity against the IDO1 enzyme in both the cancer cell lines and human dendritic cells.
• IDO1 isn’t turned on in most normal tissues hoping that this limited activity will make it a safer drug target. In addition, the biology around the target was not completely understood.
• Of the current IDO inhibitors under examination are in the very nascent stage and focusing on R&D, pharmaceutical companies are making vast investments through collaborations.
• To exemplify, one of the major pharmaceutical companies Pfizer has partnered with iTeos Therapeutics for the development of an IDO1 and tryptophan 2,3-dioxygenase 2 (TDO2) inhibitors.
• The synergistic effects of IDO inhibitors with chemotherapy hold the potential to create a new opportunity for vaccines and immunotherapy. The combination of IDO inhibitors with vaccines can redefine the cancer treatment in coming years if everything goes in the right direction as per the initial results.