Cascade Prodrug employs a platform technology that has led to our lead candidate, CPD100Li. CPD100Li is a liposomal formulated proprietary N-oxide prodrug of vinblastine, an approved cytotoxic vinca-alkaloid that has been used clinically in solid tumor and hematologic malignancies. CPD100Li is stable at normal tissue O2 levels but ‘switches’ to cytotoxic vinblastine under hypoxic conditions. By creating a novel on-off switch for vinblastine, we take advantage of tumor hypoxia and trigger drug conversion in the tumor where it’s needed, thus limiting the exposure of healthy tissue to a potent cytotoxic agent. Cascade Prodrug believes that this technology will significantly increase the maximum-tolerated-dose of chemotherapy, thereby improving outcomes in patients with solid tumors.
Cascade Prodrug’s platform brings three key therapeutic enhancements that will provide patients with improved treatment options for treating a variety of tumor types: efficacy, safety and enhanced tumor penetration. These therapeutic enhancements are made possible by our proprietary hypoxia-activated prodrug switch. CPD100Li has potent anti-tumor activity when exposed to the tumor microenvironment; it effectively masks vinblastine toxicity until it reaches the tumor, so it is much safer for the patient; encapsulation into small liposomal particles enables extended circulation times and enhanced tumor penetration.
Furthermore, CPD100Li has shown a reduction in resident and infiltrating immunosuppressive lymphocytes, with demonstrable preservation of anti-tumor macrophages and marked reduction in tumor-friendly macrophages and strong synergy when combined with an anti CTLA-4 agent in a mouse colon cancer model. This represents another potential development pathway, i.e. exploring combination therapy with immune modifying agents.