Constantine Theodoropulos, CEO and co-founder, GO Therapeutics
Constantine Theodoropulos, CEO and co-founder, GO Therapeutics

Roche plans to develop new cancer treatments based on antibody technology for which it has secured an exclusive worldwide license from GO Therapeutics, under a collaboration that the Cambridge, MA, startup said could generate for it more than $195 million.

The license agreement covers antibodies aimed at a novel undisclosed cancer-specific target, with the goal of developing and commercializing a new glycotargeting bispecific antibody.

GO’s approach to fighting cancer centers on stopping the aberrant glycosylation of both proteins and lipids, notably Tn and STn type O-linked glycans that are found in epithelial cell cancers, and not found on healthy cells—making them ideal targets for potent immune-based cell therapies such as chimeric antigen receptor T-cell (CAR-T) therapies and antibody-drug-conjugates (ADCs), the company reasons.

“We use the accessibility of these O-glycans at the plasma membrane to develop novel ‘hybrid’ epitopes that are part protein and O-glycan structure.,” GO states on its website.

GO says its tools and technology can identify sites of O-linked glycosylation on a wide range of proteins targets.

“GO’s glycoprotein targeting platform opens an exciting class of tumor-specific antigens that can help widen the therapeutic window for cancer therapies such as T-cell bispecific antibodies, CAR-T and ADCs,” GO CEO and Co-Founder Constantine Theodoropulos said in a statement. “Preclinical data show GO’s approach can provide superior specificity in targeting solid tumors over normal tissue, and demonstrate clean in-vivo toxicity profiles in the context of potent immunotherapies.”

Hans Wandall, M.D., Ph.D.
Hans Wandall, M.D., Ph.D.

Oncogenic O-glycans

The company was formed to commercialize discoveries by two University of Copenhagen researchers who serve as senior scientific consultants to GO, Hans Wandall, M.D., Ph.D., co-director of the center for glycobiology at the University of Copenhagen, and Henrik Clausen, Sci.D., the Center’s director.

Dr. Wandall served as corresponding author for a 2014 study in which researchers used cell systems generated by gene editing to show that truncation of O-glycans “directly induces oncogenic features of cell growth and invasion.

“The characteristic truncation of O-glycans found in pancreatic and most epithelial cancers is not due to somatic mutations, but is at least partly caused by epigenetic silencing of the COSMC [core 1 β3-Gal-T-specific molecular chaperone] gene by promoter hypermethylation,” according to the study, published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

“Our study demonstrates the importance of COSMC and glycosylation as a key regulator of the malignant phenotype and suggests that overexpression of truncated O-glycans is an early and sustained event during cancer development that provides a permissive environment for malignant evolution during the progression to metastasis,” Dr. Wandall and colleagues concluded. “The study provides support for targeting cancer-specific truncated O-glycans with immunotherapeutic measures.”

Roche has agreed to pay GO $9 million in upfront and near-term milestone payments, up to $186 million in payments tied to achieving additional unspecified milestones, as well as mid-single-digit to low double-digit royalties on any future product sales.

Founded in 2014, GO is based at the LabCentral shared laboratory space in Cambridge’s Kendall Square. Last year GO attracted a $5 million investment from Salubris Pharmaceutical, a holding company for Chinese-based Shenzhen Pharmaceuticals. The investment expanded Salubris’ activity into both the U.S., and accelerated its expansion into oncology.

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