Anti-Renalase Antibodies for hard-to-treat tumors
including Melanoma and Pancreatic Cancer

Bessor is advancing development of an innovative monoclonal antibody (mAb) as an immuno-oncology therapeutic against a novel target, the secreted protein renalase (RNLS). The project is collaboration with Dr.Gary Desir, Chair of Medicine at Yale, who discovered renalase and pioneered research into its potential therapeutic application. The renalase technology is exclusively licensed from Yale.   

Based on Dr. Desir’s work renalase has recently emerged as a promising target for melanoma pancreatic cancer, and other difficult to treat tumors. Several lines of evidence underscore RNLS’ potential as an important and innovative target and biomarker in melanoma and pancreatic cancer, including: 

• Over-expression of RNLS in several major cancers, including melanoma, bladder, pancreatic, HR+ breast, and non-small cell lung

• Patient clinical outcomes correlate inversely with RNLS levels

• RNLS deletion in KO mice blunts tumor growth and metastasis

• Expressed in TAMS (CD 163+), melanoma cells

• Acts through signaling pathways (MAPK, PI3K, JAK/STAT3) that protect against apoptosis 

Data suggest that anti-renalase (RNLS) mAbs uniquely affect the cancer and tumor microenvironment. These actions include, polarizing tumor associated macrophages (TAMs) to an inflammatory, tumor-killing state; increasing tumor CD4+ T cell activation, and acting directly by blocking anti-apoptotic signaling. 

Bessor has developed a lead humanized mAb, and demonstrated preclinical proof of concept in melanoma, including in checkpoint inhibitor resistant tumors. The company is extending efficacy studies to other tumors, including pancreas, bladder, lung and kidney.  

RNLS’ putative role in cancer and potential as a drug target also suggests promise as marker for patient selection to achieve maximal therapeutic benefit.

Initial Target Markets

• Melanoma. Despite recent significant advances in therapies for advanced melanoma, such as immune checkpoint inhibitors, many patients are not effectively or durably treated.  The projected number of deaths due to melanoma in the U.S. in 2021 is 7,180, according to the American Cancer Society. 

• Pancreatic Cancer. Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers with a five-year survival rate of 10 percent, according to the National Cancer Institute. The disease represents 3.2 percent of all cancers and 78 percent of all cancer deaths, with  an estimated 47,050 deaths in the US, according to the National Cancer Institute. PDAC is among the few cancer types for which survival has not markedly improved in more than 40 years. Current drug therapy is minimally effective.

Publications

Renalase overexpression in ER-positive breast cancer. InIt J Clin Exp Pathol, 2018 Mar 1;11(3):1297-1307.

Renalase expression by melanoma and tumor associated-macrophages promotes tumor growth through a STAT3-mediated mechanism. Cancer Res. 2016 May 9.

Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer. Sci Rep. 2016 Mar 14;6:22996.

Pancreatic Ductal Adenocarcinoma: From Genetics to Biology to Radiobiology to Oncoimmunology and All the Way Back to the Clinic Biochim Biophys Acta. 2014 Dec 6.

The early detection of pancreatic cancer: what will it take to diagnose and treat curable pancreatic neoplasia? Cancer Res. 2014 Jul 1;74(13):3381-9.