Navigen, Inc., is developing novel, synthetic, protease-resistant D-peptides that halt viral entry by targeting a highly conserved and critical region of the viral fusion machinery. D-peptides, composed of D-amino acids, cannot be digested by proteases in the body and, therefore, have significant therapeutic advantages, such as extended in vivo half-life and reduced immunogenicity. In our most advanced D-peptide program, we used mirror-image phage display coupled with protein design to develop chol-PIE12-trimer, a highly potent and broadly acting inhibitor of HIV-1. Chol-PIE12-trimer targets the highly conserved gp41 surface glycoprotein N-trimer region, inhibits all major circulating HIV strains, and possesses an unparalleled barrier to resistance. The pharmacokinetic profile of chol-PIE12-trimer supports the potential of monthly dosing with depot formulation. The latest preclinical results for chol-PIE12-trimer will be presented. Navigen is expanding its D-peptide discovery program to target additional viruses such as RSV and Ebola as well as non-viral targets.