The recent approvals of anti-CTLA-4 (Yervoy) and anti-PD-1 (Opdivo, Kytruda) antibodies have unequivocally demonstrated that the human immune system can cure cancer. These drugs have provided hope to patients with late-stage melanoma, non-small cell lung cancer, bladder cancer and led to the emergence of a whole new class of medicines.
Unfortunately, clinical responses to these drugs only occur in a minority of patients. In those patients that respond, strong associations are observed between the degree of CD8+ cytotoxic T cell activation and the depth of clinical response. These data have provided clinical proof of concept that CD8+ cytotoxic T cells are critical mediators of the anti-tumor immune response. Thus, combination immunotherapeutics that provide specific stimulation of CD8+ T cells may lead to dramatic synergy and patient benefit.
Our lead product candidate is a humanized monoclonal antibody that is a functional agonist of human TNFRSF25. This antibody provides highly selective and potent stimulation of ‘memory’ CD8+ cytotoxic T cells. This is the class of T cell that is responsible for eliminating tumor cells in patients. Due to the preferential specificity of PTX-35 to CD8+ T cells, this agent represents a promising candidate as a T cell costimulator in cancer patients.
Our second product candidate is a human TL1A-Ig fusion protein that can be used to cause proliferation of regulatory T cells in patients. Pre-clinical studies have demonstrated that neo-adjuvant administration of PTX-15 leads to Treg expansion and long-term tolerance toward allogeneic bone marrow transplantation, heart transplantation and islet transplantation in the absence of maintenance immunosuppression.