Codiak BioSciences, Inc. announced new preclinical data on the Company's engineered exosome precision medicine candidate, exoASO-C/EBPß. The data, which will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2022, demonstrate that exoASO-C/EBPß induces potent single-agent anti-tumor activity by repolarizing myeloid cells in the tumor and blood to induce an immune response. exoASO-C/EBPß is designed to selectively deliver antisense oligonucleotides (ASOs) to down-modulate C/EBPß, a transcription factor that regulates the immunosuppressive phenotype in tumor-associated macrophages (TAMs) and circulating myeloid derived suppressor cells (MDSCs), two subpopulations of myeloid cells.

High levels of C/EBPß expression are associated with poor prognosis in multiple cancers, including non-small cell lung cancer (NSCLC). Precise targeting of C/EBPß in MDSCs promotes the switch of TAMs from an M2 immunosuppressive phenotype to an M1, T cell attractive, anti-tumor phenotype and plays a key role in the survival and differentiation of MDSCs in order to induce an immune response. In vivo, systemic administration of exoASO-C/EBPß resulted in efficient delivery of ASOs to MDSCs resulting in > 5-fold improvement in tumors and 11 to 12-fold improvement in the circulating blood compared to delivery of a non-exosome (or “free”) ASO.

This precise cell targeting was coupled with effective silencing of C/EBPß and a remodeling of the tumor microenvironment indicative of activation of an immune response. In a variety of in vivo tumor models, exoASO-C/EBPß monotherapy generated up to 70% complete responses and, when combined with anti-PD1, significantly increased complete response rates to 90%. Notably, in a lung tumor model with widely dispersed tumors, systemic administration of exoASO-C/EBPß resulted in resolution of tumor burden throughout the body.

The profound monotherapy activity observed with exoASO-C/EBPß in multiple tumor models refractory to anti-PD-1 therapy highlights the potential of this therapy to treat multiple anti-PD1 refractory patient populations.