In 2022, the laboratories of Sam McBrayer, PhD (Asst Prof - UT Southwestern) and Nobel Laureate Bill Kaelin, MD (Prof - Harvard) demonstrated that inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) resulted in highly potent cell death among tumor cells carrying an isocitrate dehydrogenase (IDH) mutation, while sparing wildtype (unmutated) cells, in preclinical models. IDH mutations are foundational and truncal genetic alterations, present in all astrocytoma and oligodendroglioma brain tumors.

Seeking a safe and effective drug candidate for potential use in patients, Drs. McBrayer and Kaelin reached out to experts at Immunic, whose scientists have focused on developing next-generation DHODH inhibitors for decades. These scientists invented and have now almost completed phase 3 development of the drug candidate vidofludimus calcium in multiple sclerosis. That drug has been shown to be a potent inhibitor of DHODH in pre-clinical testing and also appears to have a favorable safety and tolerability profile in clinical trials in multiple sclerosis patients and other auto-immune conditions, to date. Vidofludimus calcium is an investigational compound and not approved for use in any indication.

Working together, these experts identified a series of proprietary, highly potent and brain penetrant DHODH inhibitor small molecules, which now form Gliomic’s portfolio. These molecules show promising safety and tolerability data in animals, highly selective cancer cell cytotoxicity in vitro and clear efficacy in gold standard animal xenograft models using cells derived from human patients. Our lead candidate is GLIO-1.