Making chemotherapy work again in colorectal cancer.
Evolvia BioPharma is developing first-in-class, isoform-selective PHD1 (EGLN2) inhibitors that resensitize microsatellite-stable colorectal cancer to standard-of-care chemotherapy.
EBP-4 inhibits PHD1 to block adaptive resistance — keeping tumor cells sensitive, so chemotherapy drives apoptosis.
The problem we target
Microsatellite-stable (MSS) colorectal cancer is ~95% of cases, does not respond to immunotherapy, and depends on chemotherapy that tumors eventually resist. No approved agent restores that lost chemosensitivity.
Prime
Selective PHD1 inhibition primes a latent p53 death program inside resistant tumor cells.
Activate
Standard chemotherapy (oxaliplatin, SN-38) then activates that primed program — restoring tumor-cell death.
Spare
Isoform selectivity leaves PHD2/PHD3 untouched, avoiding the HIF-driven toxicity that limited every prior PHD drug.
Why isoform-selective PHD1
Every clinical HIF-prolyl-hydroxylase inhibitor to date is pan-PHD and was developed for anemia — carrying HIF-driven cardiovascular and thrombotic liabilities. Evolvia engineers selectivity for PHD1, the isoform tied to the p53/NF-κB apoptotic axis, outside the conserved catalytic core.