Carmot Therapeutics

San Francisco, CA – October 16, 2012

Carmot Therapeutics announced today that it has won a two year SBIR grant from The National Institute of Diabetes and Digestive and Kidney Diseases to characterize and develop molecules that can selectively activate different GPCR signaling pathways.

More than a third of approved small molecule drugs target membrane proteins known as GPCRs. The types of interactions and their downstream effects are broad, and Carmot’s goal is to discover small molecules that engage specific subsets of GPCR signaling pathways, a concept known as biased agonism. These studies could lead to new drugs with superior pharmacological properties for the treatment of various metabolic disorders.

The award will fund the application of Carmot’s proprietary Chemotype Evolution technology to discover biased agonists of Class B GPCRs. Class B GPCRs can signal through both G-protein and beta-arrestin mediated pathways. However, the relative importance of these distinct pathways in promoting specific physiological outcomes is not understood, primarily due to a lack of pharmacological tools that differentiate between these two pathways. Carmot is in the unique position to address this question experimentally, having used its proprietary technology to identify chemically diverse agonists that show varying degrees of biased agonism.

Specifically, the project will seek to identify compounds that  engage the same GPCR in different ways, resulting in modulation of receptor signaling through activation of G-protein, beta-arrestin coupling, and/or receptor internalization. Select compounds will be used to determine the importance of biased agonism in stimulating relevant physiological outcomes using primary tissues samples from animal disease models. This information will be used to guide lead selection for further pre-clinical development.

Carmot’s Chemotype Evolution is a powerful drug discovery technology that rapidly identifies new lead molecules (www.carmot.us). Compared to conventional high-throughput screening, Chemotype Evolution can sample a greater repertoire of chemical diversity using smaller libraries of fragments. This approach provides an opportunity to tackle therapeutic targets that have been refractory to traditional small molecule drug discovery approaches.

For more information about Chemotype Evolution, click here.

Contact information: info@carmot.us

San Francisco, CA – December 8, 2011

Carmot Therapeutics announced today that it has been awarded a Phase II Small Business Innovation Research (SBIR) award from the National Science Foundation (NSF) to use its proprietary technology for discovering drugs that fight cancer. Carmot’s technology platform, Chemotype Evolution, is a powerful alternative to current lead-finding approaches and addresses unmet chemical needs in therapeutic discovery. One of the strengths of Chemotype Evolution is that it can convert peptides into smaller molecules with drug-like properties through a unique iterative screening paradigm.

This competitive award recognizes achievements made during Phase I and will be used to further develop and apply Carmot’s Chemotype Evolution toward an important anti-cancer target. The protein p53 blocks damaged cells from dividing; it is mutated to an inactive form in over half of human cancers. Cancer cells can also circumvent p53 by over-expressing the hdm2 protein. Hdm2 binds to p53, inhibiting its function and targeting it for degradation. Thus, molecules that block the p53-hdm2 interaction have the potential to inhibit tumor growth and may also serve to sensitize cancer cells to chemotherapy.

There has been a tremendous amount of effort in the pharmaceutical industry to identify small-molecule drugs that block the interaction between p53 and hdm2, but these have had only limited success. Peptide inhibitors of the p53-hdm2 interaction have been reported, but peptides are rapidly degraded within the body and their low cell permeability limits their utility as drugs. Carmot is using Chemotype Evolution to transform peptide inhibitors into small molecule equivalents with similar binding properties but more promise for drug development.



For more information about Chemotype Evolution, click here.

Contact information: info@carmot.us



San Francisco, CA – July 11, 2011

Carmot Therapeutics announced today that it has won an SBIR grant from The National Institute of Diabetes and Digestive and Kidney Diseases to discover molecules that selectively inhibit some lipid binding proteins without interfering with other closely related proteins. These studies could lead to new drugs for the treatment of obesity and other metabolic disorders.

The award will fund the application of Carmot’s proprietary Chemotype Evolution technology to discover small molecule inhibitors of fatty acid binding proteins (FABPs), which are important in lipid metabolism and energy storage. Chemotype Evolution is a powerful drug discovery technology that rapidly identifies new lead-like molecules (www.carmot.us). Compared to conventional high-throughput screening, Chemotype Evolution can sample a greater variety of molecular possibilities using much smaller, higher quality chemical libraries.

Specifically, the project will seek small molecules that inhibit FABP4 and FABP5 but do not inhibit other members of the class of FABPs. Animals in which either FABP4 or FABP5 have been genetically knocked out show improvements in a variety of metabolic functions, and when both proteins are eliminated the animals are remarkably resistant to obesity and type 2 diabetes. However, knocking out other members of this family of lipid binding proteins is harmful. Thus, developing selective molecules is essential.

Targeting some members of a protein family without hitting others is a difficult task using traditional methods. Chemotype Evolution is an iterative, innovative approach that is ideally suited for discovering selective next-generation therapeutics.

San Francisco, CA - April 6, 2011

Carmot Therapeutics announced today that it had won an SBIR grant from The National Cancer Institute to discover small molecule inhibitors of the NF-kB signaling pathway. The work will be conducted in collaboration with Boston University.

The award will fund the application of Carmot’s Chemotype Evolution technology to discover inhibitors of a signaling pathway important for both inflammation and cancer. Chemotype Evolution is a powerful drug discovery technology that rapidly identifies new lead-like molecules (www.carmot.us).

Specifically, the project will seek small molecules that disrupt the interaction between NEMO and IKK, which is required for phosphorylation of IkB and activation of NF-kB. The NF-kB signaling pathway is exploited in human cancers to create an inflammatory microenvironment that facilitates tumor growth and metastasis. Accordingly, mutations that enhance NF-kB activation are frequently found in human tumors. Disruption of the NEMO/IKK interaction has been shown to inhibit NF-kB signaling in vivo and promote cancer cell apoptosis, thus presenting a promising therapeutic avenue.

The work will be conducted in collaboration with Prof. Adrian Whitty’s laboratory at Boston University. Dr. Whitty is an expert in protein-protein interactions and small molecule drug discovery.

Targeting protein-protein interactions such as NEMO/IKK presents a significant untapped opportunity in therapeutic discovery. However, traditional drug discovery methods are not well-suited for this target class. Chemotype Evolution is an innovative approach with the potential to tackle protein-protein interaction targets. The goal of the SBIR-funded research is to apply Chemotype Evolution to find inhibitors of the interaction between NEMO and IKK and to test an approach that may be applicable to protein-protein interaction targets in general. 

For more information about Chemotype Evolution, click here.

Contact information: info@carmot.us



San Francisco, CA - April 12, 2010

Carmot Therapeutics, Inc. announced today that it has closed a Series A financing from The Column Group, a leading venture capital firm with a focus on early stage drug discovery companies. Carmot will use the capital to advance its proprietary drug-discovery platform, Chemotype Evolution, a novel lead finding technology that employs target-directed compound libraries generated through a unique fragment-assembly approach.

Earlier this year Carmot received an exclusive license from Sunesis Pharmaceuticals, Inc. (NASDAQ: SNSS) for Chemotype Evolution. The technology platform, which was invented by Carmot co-founders Stig K. Hansen and Daniel A. Erlanson while at Sunesis, is being used to identify promising drug candidates in a broad range of therapeutic areas. “We’re very excited to be working with The Column Group,” said Hansen and Erlanson. “The group’s deep scientific and operational expertise will be a tremendous resource as we industrialize the technology and deploy it to discover first-in-class drugs.”

Carmot has previously received grants from the National Science Foundation and the Michael J. Fox Foundation for Parkinson’s Research, but this is its first private round of funding. The Column Group’s Magnus Persson and Tim Kutzkey will join Hansen and Erlanson on the Carmot board. The company is currently located in the QB3 Mission Bay Incubator Network.

The Column Group is a leading venture capital firm dedicated to creating the next generation of biotechnology companies, each with the potential to become a leader in their respective fields. These companies will be strongly supported by The Column Group's unique and complementary skill sets, which include prominent authorities in the scientific, operational and financial arenas. The Column Group seeks to partner with exceptional scientific founders, entrepreneurs, executives and investment organizations that share its vision for building the next generation of drug discovery and development companies.

For more information about Chemotype Evolution, click here.

Contact information: info@carmot.us

San Francisco, CA - February 8, 2010

Carmot Therapeutics, Inc. and Sunesis Pharmaceuticals, Inc. (NASDAQ: SNSS) today announced that Sunesis has granted Carmot an exclusive license to its proprietary Fragment-Based Lead Discovery (FBLD) technology. Carmot will use the FBLD technology, called “Chemotype Evolution,” for identifying promising drug candidates in a broad range of therapeutic areas, including inflammatory, metabolic, and neurodegenerative diseases.  Sunesis retains full rights to the technology for use in its future internal discovery efforts.  Terms of the agreement were not disclosed.

“We believe that Chemotype Evolution has the potential to transform drug discovery and accelerate our efforts to identify novel drug candidates for challenging disease targets,” stated Stig K. Hansen, Ph.D. and Daniel A. Erlanson, Ph.D., co-founders of Carmot. Hansen and Erlanson were inventors of the technology while at Sunesis Pharmaceuticals and founded Carmot in 2008. Carmot has recently received grants from the National Science Foundation and the Michael J. Fox Foundation for Parkinson’s Research.

For more information about Chemotype Evolution, click here.

Contact information: info@carmot.us

San Francisco, CA - January 19, 2010

Carmot has been awarded a grant by The Michael J. Fox Foundation for Parkinson’s Research to develop neuroprotective drugs to reduce inflammatory damage and alpha-synuclein toxicity in Parkinson’s disease.       

The award will be used to apply Carmot’s proprietary technology to improve the pharmaceutical properties of the drug candidate CT-3. CT-3 is a potent anti-inflammatory agent that reduces oxidative damage, which contributes to neuronal degeneration. Importantly, CT-3 is safe in humans and is effective in experimental models of Parkinson’s disease. Carmot has developed a unique strategy to modify CT-3 to make it a better drug for human use. The best drug candidates will be tested in the alpha-synuclein model, which exhibits many of the hallmarks of human Parkinson’s disease. Positive results will support moving compounds towards human clinical trials.

For more information, email info@carmot.us or visit http://www.michaeljfox.org/research

San Francisco, CA - October 22, 2009

Carmot announced today that it has been awarded a Phase I Small Business Innovation Research (SBIR) award from the National Science Foundation (NSF) to use its proprietary technology to discover new anticancer drugs.

The funds will be used to apply Carmot’s Chemotype Evolution toward an important anti-cancer target. Chemotype Evolution is a powerful alternative to traditional lead-finding techniques such as high-throughput screening. Chemotype Evolution utilizes known ligands to rapidly identify new lead-like molecules.

The NSF-funded project targets an established cancer pathway. The protein p53 blocks damaged cells from dividing and is mutated to an inactive form in over half of human cancers. Cancer cells can also circumvent p53 by over-expressing the hdm2 protein. Hdm2 binds to p53, inhibiting its function and targeting it for degradation. Thus, molecules that block the p53-hdm2 interaction have the potential to inhibit tumor growth and may also serve to sensitize cancer cells to chemotherapy.

There has been a tremendous amount of effort in the pharmaceutical industry to identify drugs that block the interaction between p53 and hdm2, but with limited success. Peptide inhibitors of the p53-hdm2 interaction have been reported, but peptides do not make good anti-cancer drugs. The goal of this research is to use Chemotype Evolution to convert these peptides into drug-candidates for treating human cancers.