PIONEERING LASSO-BASED CURES
Lassogen is developing programmable lasso peptide-based drugs that address unmet needs in the area of immuno-oncology (IO). Our most advanced lasso therapeutic targets endothelin receptor type B (ETBR) to enhance the immune response in ETBR-driven cancers, while our second product is aimed at the chemokine receptor CCR4, which is involved immune suppression in the tumor microenvironment (TME).
Endothelin receptor type B in cancer. Over twenty different cancers now have been shown to overexpress ETBR and enhanced activity of ETBR in the vasculature of tumors has been found to dramatically lower the number of tumor infiltrating leukocytes (TIL's) that migrate to the TME. Low TIL counts in the TME are often associated with poor prognosis and poor patient response to immunotherapy. We are developing novel lasso peptides that increase the immune response and augment the efficacy of other immunotherapies.
See: Buckanovich, R.J., et al., Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy, Nature Med., 2008; 14(1): 28-36.
Lassogen's IO development lead, LAS-103, is a highly potent and selective antagonist of ETBR that initially is being explored to treat ETBR-driven malignancies such as ovarian cancer and triple negative breast cancer.
Lassogen's IO development lead - LAS-103
...turning immunocologically 'cold' tumors 'hot'
Chemokine receptors - challenging disease targets. Twenty chemokine receptors in the human body regulate the immune response and function. Despite the demonstrated importance of chemokine receptors and their association with disease, only three drugs that target chemokine receptors have been FDA-approved to date. The dearth of chemokine receptor drugs reflects the fact that the dominant therapeutic modalities, namely antibodies and small molecules, are poorly suited for targeting this vital class of receptors. New approaches are needed.
CC chemokine receptor 4 in cancer. The unique size, shape, and molecular volume of lasso peptides is well-aligned with high affinity binding in the pocket of chemokine receptors. We are leveraging the lasso scaffold to engineer potent ligands for CCR4, a receptor that is expressed on the surface and regulates the activity of regulatory T cells (Tregs). High levels of CCR4+ Tregs in the TME is associated with a high degree of immunosuppression, low T cell and NK cell activity, and poor prognosis for a range of different cancers. Inhibiting CCR4 activity clinically has been shown to reduce Treg populations in the TME and represents a promising approach to modulate the anti-tumor immune response. Lasso-based CCR4 antagonists are being designed as novel IO therapeutics that reduce immunosuppression in the TME by Tregs.