The vast majority of cell-penetrating peptides (CPPs) identified to date are inefficient at intracellular delivery, as they often remain trapped within the endosomal compartment. This inefficiency has limited the feasibility of intracellular biologics. Phylomers are a class of peptides derived from fragments of biodiverse microbial genomes. Phylomer peptide libraries were screened for new CPPs to improve efficient delivery of macromolecules and peptides into cells. Phylogica has developed a variety of functional assays to determine the extent of cytoplasmic delivery of these cargoes to the cytoplasm or nucleus. In some cases, these next generation Phylomer-derived CPPs allowed for potencies in the nanomolar range, as well as efficacy in animal models. These tools are now being applied in Phylogica’s internal discovery programs targeting transcription factor oncoproteins such as cMyc, NMyc and STAT5.