NEW YORK – Bridge Medicines and Cornell University on Wednesday said they have entered a licensing agreement to develop UBR5 inhibitors for difficult-to-treat cancers, including triple-negative breast cancer (TNBC).
The anti-UBR5 molecules licensed to Bridge Medicines are the product of a collaboration between Rockefeller University, Memorial Sloan Kettering, Weill Cornell Medicine, and Takeda Pharmaceutical. The collaborators comprise the Tri-Institutional Therapeutics Discovery Institute (Tri-I TDI), within which researchers developed the early-stage molecules based on discoveries at Weill Cornell's Ma Laboratory.
Cornell researchers, including Xiaojing Ma and Gang Lin, found that the cellular enzyme UBR5 plays a role in regulating certain cancers, including breast and ovarian cancers, such that they resist standard treatment with chemotherapy or immunotherapy.
In TNBC specifically, Ma, Lin, and colleagues identified UBR5-associated gene amplifications, and showed that overexpressed UBR5 facilitated tumor growth by way of immune cells within the microenvironment. The Cornell researchers confirmed overexpressed UBR5 at mRNA and protein levels in TNBC, and found that the protein was blocking immune cells from killing the cancer cells.
The researchers then showed that targeting UBR5 could improve the activity of immunotherapies such as PD-L1 checkpoint inhibitors. Within preclinical studies, they demonstrated that simultaneously targeting UBR5 and PD-L1 could diminish aggressive and treatment-resistant breast cancers.
"Work in my laboratory has demonstrated the critical importance of the UBR5 pathway in enabling major cancers to resist chemo and immunotherapies," Ma said in a statement. "This is an important unmet medical need [and] 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."
Having licensed the UBR5 inhibitors, Bridge Medicines will now be responsible for their further development. "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," Bridge Medicines CEO Bill Polvino added.
New York-headquartered Bridge Medicines didn't disclose the financial terms of the agreement.