GLP-1R and dual GLP-1R/GIPR agonists: Using Chemotype Evolution, Carmot has identified peptide-small molecule hybrid compounds that activate both GLP-1R and GIPR. These ligands have unique signaling properties resulting in enhanced glucose clearance and weight loss. Carmot is advancing these ligands for the treatment of diabetes, obesity, and NASH. Carmot plans to enter Phase 1 clinical testing in 2017. Carmot has also identified several novel series of GLP-1R agonists that replicate the functional properties of the GLP-1 peptide. An oral GLP-1 receptor (GLP-1R) agonist would dramatically expand the market and likely capture a large share of the existing multi-billion dollar incretin market.
NEMO/IKK: Targeting the interaction between NEMO and IKK to block pathological NF-kB signaling has many therapeutic applications in inflammatory and autoimmune diseases (RA, IBD, psoriasis, acute inflammatory indications, etc.) and oncology (immuno-oncology, B-cell lymphomas, and solid tumors). Using Chemotype Evolution, Carmot has identified potent small molecule and peptide-small molecule hybrid inhibitors. Carmot is now advancing these hybrid molecules to smaller molecules that contain fewer or no amino acids. Orally available small molecules would be used for chronic inflammatory indications, while larger molecules present a fast path to IV therapeutics for B-cell malignancies, immune-oncology, and acute inflammatory indications. Small, focused clinical trials are possible for certain B-cell malignancies such as Diffuse Large B-Cell Lymphoma in which patients can be stratified based on NF-kB activation status and/or presence of mutations known to activate NF-kB.
DUBs: The ubiquitin proteasome system represents an exciting and underexplored target class for treating many human diseases. Ubiquitinylation and deubiquitinylation play an important role in intra-cellular signaling in addition to regulating protein turnover. Carmot’s focus is on targeting deubiquitinating enzymes (DUBs) that remove ubiquitin from proteins targeted for degradation. Using Chemotype Evolution, Carmot is developing DUB-targeted libraries of covalent inhibitors that are being applied broadly to identify chemical scaffolds selective for specific DUBs.
Partnered Programs: Carmot has entered into collaborations with industry and academic partners. A collaboration and license agreement with Amgen, Inc. (Thousand Oaks, CA) was announced in January 2014 and extended in January 2016. A drug discovery collaboration and license agreement with Genentech was announced in July 2016.