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Calico, C4T Partner on Protein-Degrading Drugs for Age-Related Diseases

Calico and C4 Therapeutics (C4T) agreed a 5-year partnership to identify, develop, and commercialize treatments for age-related diseases, including cancer. The collaboration will hinge on C4T’s Degronimid™ platform for targeted protein degradation to identify

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Calico and C4 Therapeutics (C4T) agreed a 5-year partnership to identify, develop, and commercialize treatments for age-related diseases, including cancer. The collaboration will hinge on C4T’s Degronimid™ platform for targeted protein degradation to identify small-molecule protein degraders that eliminate disease-causing proteins. Under terms of the deal, Calico and C4T will work together on preclinical research, with Calico taking over clinical development and commercialization of products.

“We know from decades of translational research that it can be incredibly challenging to find effective pharmacologic inhibitors of many of the biologically well-validated targets, particularly in cancer,” said Hal Barron, M.D., president of R&D at Calico. “Through the alternative strategy of specifically targeting such proteins for degradation, we believe we have the opportunity to identify promising new therapeutics in cancer and in other diseases as well. We’re looking forward to collaborating with C4T’s scientists and applying their protein degradation technology to the discovery and development of effective new treatments.”

C4T was founded in late 2015 to develop Dana-Farber Cancer Institute research demonstrating that derivatives of thalidomide could be used to target specific proteins for degradation.“We are thrilled to have Calico as partners in pioneering novel therapeutics based on targeted protein degradation,” said Andrew Phillips, Ph.D., president and CSO at C4T. “Calico’s leadership team has a long record of innovation, and our combined efforts are aimed at bringing forward new options for patients affected by devastating diseases such as cancer.”

Google-backed Calico was set up in 2013 to focus on the genetics and biology of aging and the development of approaches that can slow aging and counteract age-related diseases. The firm is headed by CEO and founder, Arthur D. Levinson, Ph.D., former chairman and CEO of Genentech, and president of R&D, Hal V. Barron, M.D., who was previously Genentech’s vp and CMO.

Calico negotiated its landmark 10-year collaboration with AbbVie in 2014, through which the firms could each contribute $750 million into age-related diseases R&D and drug development. Calico has since established aging-related research, discovery, and development collaborations or license agreements with the University of Texas Southwestern, the Broad Institute, QB3, University of California, San Francisco, the Buck Institute, and The Jackson Laboratory, together with a family tree genetics collaboration with AncestryDNA™.

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01Why use a protein degrader?

Targeted protein degraders appear to have distinct advantages over more traditional inhibiting drugs. “Compared to traditional inhibitors, degraders have some potential advantages, such as eliminating scaffolding function, improving potency, and enhancing selectivity,” explains Yu Shen, PhD, director of cancer biology at AbbVie. Another major advantage of protein inhibitors is that they have the potential to treat what are referred to as undruggable proteins. As Nasveschuk points out, “There are some proteins that are just not targetable through ligands. These are ideal targets for protein degradation.” In some cases, the protein’s active site has a geometry that is not readily accessible. In other instances, although it may be possible to bind to a portion of a protein, there is no functional consequence of that binding event. “So, your inhibitor or ligand doesn’t actually do anything to the protein or modulate the disease,” Nasveschuk remarks. Protein degraders represent a novel way to target these undruggable proteins.

Source: www.genengnews.com ↗
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Peptide Therapy Guide Editorial Team

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