TH 1904 (Ovarian cancer)
A novel and targeted treatment platform in oncology is being developed based on new proprietary peptides targeting sortilin receptors. The overexpression of sortilin receptors has been documented in numerous human cancers including ovarian and breast cancers. The same has been observed in other cancers such as skin, lung, colorectal and pancreatic cancer. Targeting sortilin receptors could therefore lead to a selective delivery approach as well as a specific internalization of a number of anticancer agents that can be linked to these peptides. The use of this strategy would be a step towards personalized medicine for patients where only those likely to respond to the drug would first be identified and treated in this way, increasing the chance of a cure and minimizing health care costs. New peptide-drug conjugates generated through our platform are considered new chemical entities (NCEs) with pharmacodynamic and pharmacokinetic properties different from their parent compounds. These new anticancer agents should also induce less toxicity to non-cancerous cells that have no or only a fraction of sortilin receptors observed in some cancers.
Ovarian cancer is one of the most lethal gynecologic malignancies. Malignant epithelial tumors are the most common type of ovarian cancer, representing approximately 90% of cases. The five-year survival rate has remained close to 25%. Primary debulking surgery followed by a combination of platinum-paclitaxel-based chemotherapy is currently considered as the standard of care for advanced epithelial ovarian cancer. Other strategies have been used to treat patients with advanced ovarian cancer to prolong the short-term survival achieved following chemotherapy but with limited impact on the five-year survival rate.
Early detection and the development of novel and more effective therapeutic approaches are necessary for significant safety improvement and successful therapeutic outcomes for these patients.
Sortilin receptors are significantly overexpressed in almost all ovarian cancers.
The development of our novel therapeutic approach targeting sortilin receptors with a doxorubicin peptide conjugate (TH1904) is a potential avenue towards improving the therapeutic outcome for these patients.
In vivo, TH1904 was better tolerated than free doxorubicin and caused more potent inhibition of human ovarian tumor xenografts grown in mice. These results strongly support the future clinical use of this platform to generate novel personalized therapeutics for specific targeting of sortilin-positive tumors.