Stage: lead candidate optimization

Overview: Induction of immunogenic and regulated cell death pathways

ASN-008 is designed for intralesional delivery into cancers.   Earlier work with ASN-002 plus a number of chemotherapeutic agents demonstrated that multiple cell death pathways can be evoked through the combination use of a viral DNA/RNA, pro-cell death cytokine and certain cytotoxic small molecule drugs.   This chemo-immunotherapy combination resulted in significant lymphocytic infiltration and abscopal regression.   Early gene expression also showed intralesional induction of chemokines that recruited various dendritic cell population including cross-presenting dendritic cells into the tumor microenvironment.  These combination chemo-immunotherapy also led to enhanced regulated cell death.  Recently it has been reported that cell death that is triggered via the RIPK3 pathway can result in immunogenic cell death (1, 2).  The current lead optimization of ASN-008 builds upon earlier ASN-002 chemotherapy combination studies. The aim of this program is to develop a purely genetic approach of triggering a broader range of cell death pathways. ASN-008 is based upon the SRIP platform.

*Regulated Cell Death RCD

  1. Yatim et al, Science vol 350 Oct 2015
  2. Love Aaes et al Cell vol 15 Apr 2016