On February 7, 2022 Varsity Pharmaceuticals (Varsity), a biopharmaceutical company developing small molecule therapies that target treatment resistant cancers, reported that it has secured exclusive rights from Dana-Farber Cancer Institute, 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 (Press release, Varsity Pharmaceuticals, FEB 7, 2022, View Source [SID1234607809]).
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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 Prof. Alan D. 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.
More than 50% of primary ovarian cancers, 25% of breast cancers, and approximately 5% of pancreatic and prostate cancers are associated with HR deficiency. If development is successful, the Pol-Theta inhibitor Novobiocin could be a new treatment option for more than a 100,000 newly diagnosed cancer patients per year in the US alone. Varsity plans to start the first in-patient clinical studies of Novobiocin in 2022.
Varsity adds Novobiocin to a pipeline of small molecule candidates under development as new therapies for treatment resistant cancers.