Theratechnologies is developing a new class of treatment targeting all SORT1+ cancers by linking approved anticancer drugs to proprietary peptides that specifically bind to the sortilin receptor. The normal role of sortilin is to act as a cellular shuttle system, moving proteins across the cell membrane via the endosomal/lysosomal pathway. The peptide-drug conjugate (PDC) is internalized by the receptor and the therapeutic agent is released inside the cell.
The sortilin receptor is preferentially expressed on cancer cells compared to healthy tissue. The expression of the sortilin receptor has been documented in multiple cancers, including ovarian, endometrial, triple negative breast, melanoma, lung, colorectal and pancreatic cancers, among others.
As opposed to classic chemotherapy which is freely released in the organism reaching both healthy and cancerous cells, the cytotoxic payload conjugated to our PDCs is delivered selectively to the sortilin receptor on cancer cells and is then rapidly internalized inside the cancer cell and the cytotoxic is released. Based on pre-clinical trial, it could lead to an improved safety profile, higher cytotoxic payload and throughput concentrations of cytotoxic inside the cancer cells. It was also observed in pre-clinical trials that our PDCs bypass a chemo efflux pump (multidrug resistance protein or MDR1), a known resistance mechanism, the resistance mechanism utilizing the endocytic pathway to carry the cytotoxic payload into the cancer cell. Furthermore, it was found to have an impact on vasculogenic mimicry, another mechanism associated with resistance to existing cancer therapies. Vasculogenic mimicry is a sortilin dependent process where cancer cells form channels to allow blood and nutrients to flow into parts of the tumor to nourish its growth. To date, there are no effective drugs available targeting the vasculogenic mimicry process.
PDCs based on the SORT1+ Technology™ can be conjugated to multiple established anti-cancer drugs and could lead to easier treatment customization and be more sustainable than antibody drug conjugates.
New peptide-drug conjugates (PDC) generated through our SORT1+ Technology™ are considered new chemical entities (NCEs) with pharmacodynamic and pharmacokinetic properties different from their parent compounds.