GlyTR Therapeutics

September 20, 2016 By Applied Innovation

Professor and inventor Michael Demetriou

Professor and inventor Michael Demetriou has been studying immune-related diseases and cancers long before founding GlyTR Therapeutics in 2015. Prof. Demetriou’s research focuses on aberrant protein glycosylation that occurs in diseased cells. Glycosylation, the addition of sugars or glycans to proteins and other biomolecules, is an important method cells use to define the structure, function, and transportation of the molecule. The glycosylation process is universally disrupted in cancer, resulting in a class of molecules termed tumor-associated carbohydrate antigens (TACAs). Prof. Demetriou and Dr. Raymond Zhou, a postdoctoral researcher in his lab, believe TACAs can be exploited as unique cancer targets. They have developed a novel therapeutic platform that addresses the abnormal glycosylation of affected cells. The molecules designed by these researchers take advantage of the human body’s natural defense mechanism, the immune system, to selectively identify and eliminate the cancer. Their solution is unlike traditional cancer fighting methods, which use radiation or toxic drugs to kill tumor cells. Current radiation and chemotherapies are inherently non-tumor-specific, have widespread side-effects, and variable effectiveness across all types of cancers.

The cancer therapeutic platform designed by the Demetriou group, termed GlyTR (short for Glycan-dependent T cell Recruiter), is a novel bispecific molecule that on one end, recruits and binds T cells, and on the opposite end, targets cancer cells via their hallmark abnormal sugars. Through this method, T cells, the lymphatic cell type of the immune system that destroys infected or damaged cells, become directly linked to their target, facilitating elimination of the tumor.
A second therapeutic approach also being explored by the Demetriou research group is engineered T cells. These designer T cells would directly target the TACAs of the cancer cells. Both the GlyTR bispecific molecule and engineered immune cell approaches are amenable to combination therapies and personalized medicine to combat cancer. Prof. Demetriou explains that by understanding the glycobiology of cancers, they will “have the ability to take an individual’s cancer and type them for the type of carbohydrate structures that are abnormal in that cancer, then select which treatment.” This approach affords the best therapeutic option for a patient’s unique case, and gives them the greatest chance for success and survival.

Prof. Demetriou describes his personal mission and that of his lab’s researchers is to “take what you learn from the most basic, fundamental principles to actually being a product that is used to help people.” This “bench to bedside” approach is not just talk. In 2012, Prof. Demetriou created Glixis Therapeutics, a company that focuses on understanding and treating autoimmune diseases. With the early success of Glixis, Prof. Demetriou turned his attention to the promising work of the GlyTR therapeutic. Like a veteran businessman, he explains that “first you have to have the idea,” after that, the process “requires different skills all along the way,” and “to get to that final product stage, you really need a company and investors.” With this in mind, after coming up with the concept and beginning preliminary in vitro studies of the GlyTR molecule, Prof. Demetriou sought to connect with the business community to move the technology off the bench. He and his co-inventor, Dr. Zhou, participated in the ZAP! program (see page 17 for info on the Zap! program), where they pitched their concept and connected with experienced startup professional, Raksha Shah. Not long after this meeting, the inventors and Mrs. Shah founded GlyTR Therapeutics.

One of the company’s first successes in its formative year was being awarded a Commercialization Grant through Applied Innovation (see page 4 to read more about the Commercialization Grant and this year’s awardees).  This funding afforded the resources to develop the GlyTR “proof of product” by initiating cell studies, as well as continued optimization of the molecule. Preliminary results of the performance of GlyTR in an in vitro tumor killing assay, shows that the GlyTR approach (A) kills diverse types of cancer cells, including B cell lymphoma, myeloma, and colon, liver, breast, and cervical carcinomas, (B) is specifically targeting the TACAs of the tumor cells, and (C) the killing of these cells occurs in a dose-dependent manner, with respect to both the GlyTR molecule and immune cell.

Having achieved the early in vitro benchmarks, Prof. Demetriou and GlyTR Therapeutics’ CEO, Raksha Shah, are moving the company into its next phase: obtaining more funding to perform toxicity and animal studies. After demonstrating success in animal models, they will submit an Investigational New Drug (IND) application to the FDA to initiate human clinical trials.
To learn more about GlyTR Therapeutics, please visit: glytrtherapeutics.com

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