SUMMARY OF INVENTION
We have developed both high-affinity mouse and human (Alivamab mouse) antibodies against the glycosylation binding domain of human Galectin-3 (Gal3). These antibodies cause direct inhibition of cancer growth and metastasis in at least two serious and common cancers in dire need of new treatment options. Chronic Gal3 blocking with our antibodies has been well tolerated in mouse models cross reactive with the human protein.
In cancer, Gal3 has been implicated in the pathogenesis of malignant tumors including ovarian, lung, and pancreatic cancers. It enhances angiogenesis, promotes drug resistance, and inhibits the cytotoxic effects of T-cells against cancer cells, as part of the suppressive microenvironment. Gal3 presence on exosomes also may enhance implantation of malignant cells in the establishment of distant metastases, as well as promotion of metastatic tumor colonization. Given this involvement in general tumor biology and the fact that our anti-Gal3 antibodies were very well tolerated in mouse models, they are excellent candidates for combination therapy with immune checkpoint inhibitors or adoptive cellular therapies after single agent safety is established.
Gal3 inhibition has been proposed in a variety of non-cancer inflammatory diseases, including Non-Alcoholic Steatohepatitis (NASH) and primary pulmonary fibrosis. Currently, there are no anti-Gal3 inhibitors targeting the carbohydrate-binding domain in advanced clinical trials. Small inhibitory molecules against Gal3 require high concentrations and have higher toxicity risk because of intracellular and blood brain barrier penetration.
- Extensive data produced with mouse antibodies—straightforward path to replicate this data with the human antibody for quick go/no-go decisions
- Both human and mouse Gal3 antibodies cross-react with mouse Gal3
- Neither antibody significantly binds Galectin-1, Galectin-7, or Galectin-9, which have the highest homology in the antibody binding region with Gal3, thereby reducing likelihood of off-target effects
- Potential for non-cancer applications (i.e. Non-Alcoholic Steatohepatitis (NASH) and primary pulmonary fibrosis)
SK2016-097: National applications pending in Canada, Europe, Japan and Australia; SK2020-011: PCT application PCT/US2021/040051 pending, filed on July 1, 2021
Direct inhibition of cancer growth and metastasis in Ovarian cancer and Pancreatic Cancer, two devastating cancers in the US (Serous Ovarian Cancer >20,000 new cases, >15,000 deaths annually in US; Pancreatic Cancer 60,000 new cases and 48,000 deaths annually). Potential additional applications include Pulmonary Fibrosis (>30,000 new cases in US annually) and NASH (prevalence: ~16M in US).
- David Spriggs, MD, C0-Leader Gynecologic Cancers and Member, Chief Scientific Council, Massachusetts General Hospital; formerly at Memorial Sloan Kettering
- Stasenko, et al. Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies. Sci Rep. 2021; 11: 3718. (PubMed link)
Imke Ehlers, PhD, CLP
Director, Business Development and Licensing, Memorial Sloan Kettering Cancer Center
[email protected]; C (646) 457-7626
MSK Internal Code: SK2016-097 / SK2020-011