More Anti-Tumor Activity, Fewer Side Effects for Patients
PCS6422 Targets Colorectal and Metastatic Breast Cancer
PCS6422 (eniluracil) is a potent, irreversible inhibitor of dihydropyrimidine dehydrogenase (DPD) that is intended for use in combination with Xeloda® for the treatment of advanced gastrointestinal (GI) tumors. DPD is an enzyme that rapidly metabolizes 5-FU (a drug that is commonly used to treat multiple solid tumors) into inactive metabolites, such as α-fluoro-β-alanine (F-Bal).
The presence of F-Bal is known to decrease the antitumor activity of 5-FU and cause toxicities and adverse side effects associated with 5-FU, such as Hand-Foot Syndrome (HFS). HFS is a serious condition that affects patients’ quality of life and requires interruptions and adjustments to treatment dosage or even the discontinuation of therapy, thus compromising the efficiency of their anti-tumor treatment.
Xeloda® Combination Therapy
Xeloda® (capecitabine) is an oral prodrug of 5-FU that is used as first-line therapy for metastatic colorectal and breast cancer. However, the use of capecitabine is limited by adverse side effects such as HFS, which develops in up to 60 percent of patients.
Preclinical studies using human breast, pancreatic, and colorectal cancer cells show that the combination of PCS6422 and capecitabine can improve the antitumor activity of capecitabine thanks to PCS6422’s ability to inhibit DPD, reducing the 5-FU side effects related to F-Bal and significantly lowering the dose of capecitabine that’s required to be effective.
Other DPD enzyme inhibitors
Other DPD enzyme inhibitors that act as competitive reversible inhibitors have been approved only for use outside the U.S. These agents, however, must be administered simultaneously with 5-FU or capecitabine to inhibit the breakdown of 5-FU by DPD and improve the efficacy and safety profile of 5-FU. Conversely, there is evidence that suggests administering DPD inhibitors directly with 5-FU may also decrease the antitumor activity of 5-FU.
As an irreversible inactivator of DPD, PCS6422 can safely be administered a day prior to chemotherapy. One dose of PCS6422 irreversibly blocks DPD activity for up to two weeks, resulting in higher potency of 5-FU and better tumor response along with a decrease in F-Bal quantities.
We entered into a license agreement with Elion Oncology, Inc. on August 23, 2020. Under the Elion License Agreement, we received an exclusive contingent license to develop, manufacture, and commercialize PCS6422 globally.