exoASO™-STAT6 is an exosome therapeutic candidate engineered using our engEx™ Platform to overexpress Codiak’s novel protein scaffold, PTGFRN, to selectively target uptake in M2 polarized tumor-associated macrophages.
Developed via Codiak’s proprietary engEx Platform, exoASO-STAT6 is surface-loaded with an antisense oligonucleotide (ASO) targeting the STAT6 transcription factor. Transcription factors such as STAT6 that regulate gene families are ideal targets for potent repolarizing of tumor-associated macrophages, yet they have been very challenging to drug with common drug modalities. We have designed exoASO-STAT6 to allow for the necessary delivery specificity of the STAT6 ASO to the M2 macrophages to selectively repolarize these cells, resulting in strong pre-clinical single agent anti-tumor activity not possible with free ASO and not observed with other pathway indicators. Our preclinical studies with exoASO-STAT6 showed preferential uptake into M2 polarized macrophages, increased selective delivery, and potency compared to free ASO and potent reduction in STAT6 mRNA, which led to a distinct decrease in expression of M2 genes and increase in expression of M1 genes.
We are developing intravenously-administered exoASO-STAT6 for various myeloid rich cancers, including hepatocellular carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, lung adenocarcinoma, uveal melanoma, glioma, thyroid cancer, and ovarian cancer.See the science