TH 1902 (Triple Negative Breast Cancer(TNBC))
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.
Breast cancer is the second-most frequent tumor worldwide with close to 2,100,000 cases and about 675,000 deaths in 2018. Approximately 10% to 20% of these patients will be diagnosed with a sub-group of breast cancers defined by the lack of expression and/or amplification of receptors for estrogen, progesterone, and human epidermal growth factor receptor. These triple negative breast cancers (TNBC) present with varied natural histories but are collectively associated with poor prognosis, high risk of relapse, a short progression-free survival (PFS) and overall survival (OS). Women with TNBC have an increased likelihood of distant recurrence and death compared to women with other types of breast cancer. As many as 50% of patients diagnosed with early-stage TNBC (stages I to III) experience disease recurrence, and 37% die in the first 5 years after surgery. Similarly, patients with metastatic TNBC have short PFS after the failure of first-line chemotherapy (median PFS, 3 to 4 months), indicating the pressing need for the development of new treatments for TNBC. Existing therapies (hormonal or trastuzumab-based therapy), which are based on targeting the ER or HER2 oncogenes, cannot be expected to be useful for TNBC given the lack of hormone receptor expression and HER2 protein overexpression. Therefore, TNBC has a more severe prognosis than other subtypes of breast cancers because of the lack of potential targets.
However, sortilin receptors are significantly overexpressed in TNBC . Consequently, creating a novel and more effective therapeutic approach by targeting sortilin-positive TNBC with our docetaxel-peptide conjugate (TH1902) provides a clinical opportunity for safety improvement and successful therapeutic outcomes for these patients.
Taken together, our pre-clinical data demonstrate high in vivo efficacy and safety in using TH1902 against TNBC via a sortilin receptor-mediated mechanism. This allows for selective targeting of sortilin-positive breast cancers and makes TH1902 a promising avenue for personalized therapy in the treatment of TNBC.