| CAMBRIDGE, Mass., Dec. 6, 2018 – Casma Therapeutics, Inc. today announced an exclusive and nonexclusive license to technology developed at The University of Texas Southwestern Medical Center that will advance the company’s drive to harness the natural cellular processes of autophagy to design powerful new medicines for a broad range of diseases.The license includes commercial rights to a patent application covering small molecules, and to screening assay technologies developed by Beth Levine, M.D. and Jef De Brabander, Ph.D. to aid discovery of small molecules that can disrupt the interaction between the BECN1 protein and a negative regulator, BCL2. This crucial molecular pathway influences the rate of autophagy, the natural process by which cells break down surplus or dysfunctional proteins, pathogens and organelles such as mitochondria.
Levine, a co-founder of Casma, reported in Nature earlier this year that mice which had been genetically engineered to have a higher basal autophagy rate lived about 10 percent longer than their litter-mates and were less likely to develop age-related spontaneous cancers and age-related pathological changes in the heart and the kidney. The paper also noted that this genetic mutation rescued premature lethality and infertility in mice deficient in the anti-aging protein klotho. The Nature paper suggests that disrupting BECN1-BCL2 interactions could be a promising target for drug development.
A paper published in 2017 in PLOS Genetics found that the mutation also conferred protection against mouse models of neurodegeneration similar to Alzheimer’s disease.
“This agreement gives us access to exciting new tools to speed discovery of drugs that can induce autophagy and potentially halt or reverse the progression of disease,” said Jeff Saunders, Ph.D., Casma’s senior vice president of drug discovery. “The research by Beth and Jef lays out a clear path for development of a new class of drugs that leverage autophagy to address both rare genetic diseases and more common conditions, such as inflammatory disorders and neurodegeneration.”
Dr. Levine is director of the Center for Autophagy Research and the Charles Cameron Sprague Distinguished Chair in Biomedical Science at The University of Texas Southwestern Medical Center. Dr. Levine, who is an investigator at the Howard Hughes Medical Institute, first discovered BECN1 and described its role in mammalian autophagy 20 years ago.
Dr. Levine serves on Casma’s scientific advisory board, holds founder’s shares in the company and will receive licensing revenue from Casma through UT Southwestern. Dr. De Brabander will also receive licensing revenue from Casma through UT Southwestern. Neither Casma or Third Rock sponsored the research published in Nature or PLOS Genetics.
About Casma Therapeutics
Casma Therapeutics is harnessing the natural cellular process of autophagy to open vast new target areas for drug discovery and development. Casma uses several approaches to intervene at strategic points throughout the autophagy system to improve the cellular process of clearing out unwanted proteins, organelles and invading pathogens. By boosting autophagy, Casma expects to be able to arrest or reverse the progression of lysosomal storage disorders, muscle disorders, inflammatory disorders and neurodegeneration, among other indications. Casma was launched in 2018 by Third Rock Ventures and is based in Cambridge, Mass. For more information, please visit www.casmatx.com.
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