DEM301 is a clinical development candidate, an antibody-drug conjugate (ADC) composed of an afucosylated monoclonal antibody (targeting DEM-T02), conjugated to clinically validated linker-payload. DEM BioPharma is currently evaluating DEM-301 in pre-clinical pharmacology and toxicology studies and has initiated DEM-301 CMC process development and manufacturing in anticipation of Investigational New Drug Application Mid 2026.
DEM-T02 is a novel plasma membrane-associated glycoprotein, primarily found on mucosal epithelial cells. Identified as a 'DEM' signal in a CRISPRa screen of tumor cells, it has been reported to play roles in cell adhesion and myeloid cell suppression. DEM-T02 is notably overexpressed in colorectal, gastric, liver, pancreatic, cervical, and testicular cancers and has been associated with malignant phenotypes in multiple solid tumors. Its expression is negatively correlated with disease progression, underscoring its potential significance in tumor biology.
DEM-T06 was identified through our macrophage-based screening platform at DEM, aimed at discovering regulators of macrophage activation and polarization in the context of tumors and immunosuppressive tumor microenvironments. DEM-T06 is an intracellular target predominantly expressed in myeloid cell lineages. Its inhibition leads to the activation of the TLR-MyD88 signaling pathway, resulting in an increased production of pro-inflammatory cytokines, including TNFα, IL-12, and IL-6. Notably, this activation is localized primarily within the tumor microenvironment, minimizing off-target effects and offering a significant advantage over traditional systemic TLR-MyD88 activators.
The DEM-T06 program is currently in the Hit-to-Lead stage, with multiple highly potent and selective compound series developing in parallel.