SQ3370 Activates Cytotoxic Drug via Click Chemistry at Tumor and Elicits Sustained Responses in Injected and Non-Injected Lesions

Abstract

While systemic immuno-oncology therapies have shown remarkable success, only a limited subset of patients benefit from them. The Click Activated Protodrugs Against Cancer (CAPAC) platform is a click chemistry-based approach that activates cancer drugs at a specific tumor with minimal systemic toxicity. The CAPAC Platform is agnostic to tumor characteristics that can vary across patients and hence applicable to several types of tumors. The benefits of SQ3370 (lead candidate of CAPAC) are described to achieve systemic anti-tumor responses in mice bearing two tumors. SQ3370 consists of a biopolymer, injected in a single lesion, followed by systemic doses of an attenuated protodrug of doxorubicin (Dox). SQ3370 is well-tolerated at 5.9-times the maximum dose of conventional Dox, increased survival by 63% and induces a systemic anti-tumor response against injected and non-injected lesions. The sustained anti-tumor response also correlates with immune activation measured at both lesions. SQ3370 can potentially benefit patients with micro-metastatic lesions.