Lassogen is developing a new therapeutic modality based on lasso peptides that we are programming to treat difficult diseases such as cancer and autoimmune disorders. Lasso peptides are naturally produced by bacteria and represent a unique, vast, untapped source of novel molecular diversity for drug discovery and development. The distinctive lasso fold and 3D topology of lasso peptides engender these scaffolds with beneficial properties (protease, low pH, heat stability) and potent biological activity against challenging targets such as G protein-coupled receptors. Lasso peptides also display an increasingly wide range of mechanisms of action, such as intracellular enzyme inhibition, extracellular protein binding, biosynthesis intermediate binding, and cell-surface receptor modulation. Lassogen’s proprietary cutting-edge platform enables high throughput production and optimization of our innovative lasso-based therapeutics. Our founding team has developed a genome mining algorithm using machine learning, which has revealed the extreme prevalence of highly diverse lasso peptides across most bacterial phyla. Thus, millions of lasso peptides in nature serve as excellent starting points for Lassogen as we advance this new class of therapeutics. Our first products are targeting GPCRs for immuno-oncology applications. For example, LAS-103 is a potent and selective antagonist of endothelin type B receptor (ETB). Blocking ETB opens up tumors to infiltration of lymphocytes and turns "cold" tumors "hot" in cancers that overexpress ETB. Combinations of LAS-103 with other immunotherapies thus represents a new approach for treating challenging malignancies such as ovarian cancer and triple negative breast cancer.