United States of America based
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.
TechnologiesAI Companies (Drug Discovery)
Peptides are modular chains of amino acids that serve as natural ligands for many receptors in the body and offer attractive attributes for new drug discovery. The ability to create large peptide diversity libraries offers the potential to develop novel therapeutics with high target affinity and specificity. However, low in vivo stability and poor pharmacokinetics have greatly limited the application of peptides in pharmaceutical development. Lassogen aims to change this paradigm through a new class of remarkable peptides uncovered in nature.
Gifts from nature. Lasso peptides are naturally produced by bacteria and possess a distinctive threaded lariat fold that offers a 3D array of functionality for engaging biological targets. This unique lasso structure engenders these systems with beneficial properties such as high stability (to proteases, low pH, and heat) and potent biological activities. Our new genome mining algorithms have been trained using machine learning and indicate that millions of diverse lasso peptides are likely to reside in nature - a veritable untapped goldmine of new activities and novel mechanisms of action for drug discovery and development.
Linear peptides are strings of amino acids that are easily degraded in vivo
Bacteria convert linear peptides into highly stable, bioactive lasso peptides
Millions in nature
Unique 3D structure
Infinite lasso diversity
Ideal size and shape for receptor binding
Diverse lasso structures have translated into a wide range of mechanisms of action, including activity vs challenging G protein-coupled receptors (GPCRs). Many therapeutic applications of lasso peptides can be envisioned.
Lassogen’s cutting-edge platform integrates genomics, advanced synthetic biology, and AI-data analytics to enable accelerated discovery, optimization, and production of our novel lasso peptide-based therapeutics. Our AI-driven algorithms mine genomic space and predict lasso biosynthesis pathway genes. Cell-free biology rapidly converts lasso sequence data into molecules that can be screened. Hits are optimized through lasso evolution methods. Lassos of interest are scaled for development through engineered fermentation strains.
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