Technology

RNA INTERFERENCE HAS A POWERFUL ROLE TO PLAY IN CANCER THERAPY

As precision medicines for the treatment of cancer, siRNAs can be designed precisely to target any expressed disease-related mRNA, including oncogenes, tumor suppressors, and immune checkpoints. Our approach expands the therapeutic utility of antibodies and may overcome dose-limiting toxicities associated with small molecule cytotoxics traditionally used in ADCs. Moreover, when delivered via an antibody having anti-tumor activity, there is significant potential for the siRNA “payload” to have additive and even synergistic activity.

ADVANTAGES OF ASCs™

ASCs take advantage of the specificity of antibodies for targeted delivery and exploit cell surface receptors for internalization of siRNA payloads against key genetic drivers of disease. ASCs have drug-like properties similar to antibodies and ADCs, which can dramatically enhance the biodistribution and cellular selectivity of siRNA delivery.  Because of the siRNA payload is designed precisely to inhibit the expression of only the targeted disease-related gene product, ASCs also have a potentially larger therapeutic window relative to ADCs with their non-specific payloads of cytotoxic agents. Delivering siRNA using ASC technology also avoids the lipid-based toxicities that have been associated lipid nanoparticles another commonly used delivery modality for siRNAs. The dual specificity of targeted delivery taken together with the inherent specificity of rationally designed siRNAs provides unmatched precision to our therapeutic platform.

POTENTIAL APPLICATION OF ASCs TO OTHER SERIOUS DISEASES

The precise nature of the Avidity ASC platform avoids one of the key limitations of antibody-drug conjugates, the requirement for a very potent small molecule payload, necessitating the use of DNA-damaging agents or other cytotoxics for anti-tumor efficacy. In contrast, siRNAs are highly specific and can be generated with picomolar IC50 values. Once loaded into the RNA inducible silencing complex (RISC), those siRNAs can inhibit mRNA expression for days or even weeks. With the ability to deliver selective inhibitors of disease-related gene products, our ASC platform opens up the potential to inhibit mRNA expression of other disease-specific targets such as those associated with inflammation, fibrosis or autoimmune disease.