Varsity Pharma in-licenses Pol-Theta inhibitor novobiocin

UK biopharma company Varsity Pharmaceuticals has secured exclusive rights from Dana-Farber Cancer Institute (DFCI), a world-leading cancer treatment and research institute, to develop and commercialize novobiocin, a potential first-in-class DNA polymerase theta inhibitor for the treatment of homologous recombination (HR) deficient cancers.

Homologous recombination deficiency is where the body is unable to repair double strand breaks in DNA due to mutations in genes such as BRCA1 and BRCA2. Pol-Theta is an enzyme that can repair double strand breaks that recently emerged as a new cancer specific DNA Damage Response target that compensates for the loss of HR function in HR deficient cancers such as ovarian, breast, pancreatic and prostate cancer. Whilst PARP enzyme inhibitors have seen some success in the treatment of HR deficient cancers, PARP inhibitor drug resistance is emerging as a significant barrier to their effectiveness.

Research led by Professor Alan D’Andrea and published in  Nature Cancer (Zhou et al. 2021) demonstrated that novobiocin, a drug previously used as an antibiotic, is a potent Pol-Theta enzyme inhibitor that can be used alone or in combination with PARP inhibitors to treat HR-deficient tumors, even after they have become resistant to PARP inhibitor therapy.