On July 28, 2021 Bridge Medicines and Cornell University reported an exclusive license agreement to develop UBR5 Inhibitors for the treatment of certain difficult-to-treat cancers such as triple-negative breast cancer (TNBC) (Press release, Bridge Medicines, JUL 28, 2021, View Source [SID1234585273]).

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UBR5 is a cellular enzyme (an E3 ubiquitin ligase) that is involved in the labeling of other proteins within a cell to designate them for destruction. UBR5 has recently been shown to be a key regulator in certain cancers, such as breast and ovarian cancers, enabling the cancer cells to survive and resist standard treatments.

Pioneering research by Dr. Xiaojing Ma and Dr. Gang Lin and their colleagues at Weill Cornell Medicine have identified a distinctive and profound role of UBR5 in the growth and metastasis of triple negative breast cancer (TNBC). An analysis of TNBC specimens revealed strong gene amplifications of UBR5 associated with the disease. UBR5 overexpression in TNBC tissues was confirmed at mRNA and protein levels. Dr. Ma and his colleagues discovered that tumor-derived UBR5 facilitated tumor growth in a manner dependent upon immune cells within the microenvironment, rendering them less able to kill the cancer cell. Consequently, attacking the UBR5 target may work well in combination with other immune regulators, such as those that target the PD-L1 pathway. The combined targeting of UBR5 and PD-L1 yields strong therapeutic benefit to tumor-bearing hosts in preclinical studies. Collectively, these data support targeting UBR5 as a novel immunotherapy to treat highly aggressive breast cancers that resist conventional therapies.

"Work in my laboratory has demonstrated the critical importance of the UBR5 pathway in enabling major cancers to resist chemo- and immuno-therapies," said Dr. Xiaojing Ma, professor of microbiology and immunology at Weill Cornell Medicine. "This resistance results in advancing cancers and ultimately death in many patients despite currently available treatments. This is an important unmet medical need. We believe that by developing an effective anti-UBR5 approach, we may be able to provide life-saving outcomes for patients who are out of options."

The Tri-Institutional Therapeutics Discovery Institute, Inc. (Tri-I TDI) advanced the pioneering discoveries from the Ma Laboratory into early-stage drug molecules. Tri-I TDI’s mission is to work with innovative scientists at its founding institutions, The Rockefeller University, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medicine, in a close collaboration with Takeda Pharmaceutical Company Ltd, to accelerate the discovery of new drug molecules. Bridge Medicines will further develop and advance these molecules with the goal of bringing a new treatment to patients.

"We are very excited to bring the UBR5 program into Bridge Medicines," said Bill Polvino, CEO of Bridge Medicines. "The preclinical data are very compelling, and we look forward to developing a novel, first in class therapy for cancers that resist current treatments, such as triple negative breast and ovarian cancers."

"Drug discovery is essential for advancing healthcare, ensuring the translation of cutting-edge science into powerful medicines that are available to patients who need it most," said Dr. John Leonard, senior associate dean for innovation and initiatives at Weill Cornell Medicine. "The Tri-I TDI-Bridge Medicines continuum is invaluable to realizing that promise and serves as a vital component of the Weill Cornell Medicine Enterprise Innovation ecosystem. We are excited that the UBR5 program, based on Drs. Ma and Lin’s groundbreaking research, has achieved this important milestone with Bridge Medicines."

Weill Cornell Medicine Enterprise Innovation accelerates the best of biomedical innovation to market, translating groundbreaking research into revolutionary care. Enterprise Innovation provides a bridge between academic researchers and industry stakeholders, brokering engagements and alliances, engaging with and educating faculty about biotech commercialization and business development—which includes patenting, licensing, and marketing—and developing entrepreneurial programming, education, mentoring, and other resources.

About TNBC
Triple-negative breast cancer (TNBC), as defined by the negative expression of the estrogen receptor (ER) and progesterone receptor (PR) as well as human epidermal growth factor receptor-2 (HER-2), represents approximately 15% to 20% of all invasive breast carcinomas. TNBCs are highly aggressive with large tumor mass, high nuclear grade, and increased lymph node involvement at the time of diagnosis, contributing to the highest risk of recurrence and metastasis of all breast cancer types at an early time. Particularly, because of the heterogeneity and no well-defined molecular targets, patients with metastatic TNBC have a poor 5-year survival despite standard treatment. It is urgent to discover new therapeutic targets that are involved in shaping the highly aggressive behavior of TNBC.

About Tri-I TDI
The Tri-I TDI connects researchers from Memorial Sloan Kettering Cancer Center, The Rockefeller University and Weill Cornell Medicine with collaborators from across the globe to remove barriers that impede drug discovery in academic settings. Tri-I TDI empowers the Tri-I community to advance their groundbreaking biological discoveries through preclinical studies by providing industrial-scale technical support for academic projects, making it possible to rapidly assess the utility of specific therapeutic targets in disease-relevant contexts. Working in close collaboration with Takeda Pharmaceutical Company, Ltd. and Bridge Medicines, Inc., Tri-I TDI accelerates the discovery of next generation drugs. For more information about Tri-I TDI, please visit www.tritdi.org or contact [email protected].