Date: 2015-03-04
Type of information: Development agreement
Compound: anti-PD-L1 and anti-GITR antibody research programs
Company: Checkpoint Therapeutics (USA - NY) TG Therapeutics (USA - NY)
Therapeutic area: Cancer - Oncology
Type agreement: development commercialisation
Action mechanism: monoclonal antibody/kinase inhibitor. Anti-PD-L1 antibodies target programmed cell death ligand 1 (PD-L1). Signals from PD-L1 on tumor cells and in tumor microenvironment help those tumors avoid immune attack and elimination by preventing activation of tumor specific effector T-cells. Anti-PD-L1 antibodies are designed to block that signal permitting effector T-cells to attack the cancer. Anti-GITR antibodies target glucocorticoid-induced tumor necrosis factor receptor related protein (GITR), which is regularly expressed on the surface of regulatory T-cells (Tregs) and is expressed on the surface of effector T-cells after their activation. Modulation of GITR with agonistic antibodies has been shown to amplify the antitumor immune responses in animal models via multiple mechanisms. Anti-GITR antibodies are designed to activate the GITR receptor thereby increasing the proliferation and function of effector T cells. At the same time, ligation of GITR on surface of Tregs could abrogate suppressive function of these cells on tumor specific effector T-cells thus further augmenting T-cell immune response. While targeting PD-1/PD-L1 axes alone has already demonstrated impressive anticancer efficacy and durable responses in humans, its efficacy appears to be limited to certain patients. It is believed the effects of anti-PD-L1 intervention can be enhanced by utilizing a co-stimulatory antibody, like one targeting GITR, that can turn on tumor specific effector T-cells. Combining immunotherapies like anti-PD-L1 that counters the tumor\'s immune-evading defense system with an anti-GITR that activates effector T-cells, represents a rational approach to use the body\'s own immune system to help fight cancer. Pre-clinical research on the combination of the two approaches has yielded encouraging results to support synergistic potential of this combination. TG-1101 (ublituximab) is a novel, glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. TGR-1202 is an orally available PI3K delta inhibitor. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-lymphocytes. Both TG-1101 and TGR-1202 are in clinical development for patients with hematologic malignancies.
Disease: hematological malignancies
Details: * On March 4, 2015, TG Therapeutics announced an agreement with Checkpoint Therapeutics, a newly formed subsidiary of Coronado Biosciences, to develop and commercialize Checkpoint\'s fully human anti-PD-L1 and anti-GITR antibody research programs in the field of hematological malignancies. Checkpoint will develop and commercialize these antibodies in solid tumors. The antibodies were generated in the laboratory of Dr. Wayne Marasco, MD, PhD, a Professor in the Department of Cancer Immunology and AIDs at Dana-Farber Cancer Institute (Dana-Farber). Both programs are currently in pre-clinical development and are anticipated to enter the clinic in 2016. Mr. Michael S. Weiss, Executive Chairman, Interim CEO and President stated,\' we will continue to build our portfolio to optimize our combination approach to provide the best possible outcomes to patients with B-cell malignancies without the need to use harsh chemotherapy, ideally pushing toward a cure. It is believed that these two antibodies can work synergistically together and we believe that adding them to the already marked activity we are seeing with our proprietary combination of TG-1101 (ublituximab) and TGR-1202 across CLL and NHL could greatly enhance the therapeutic benefit to patients with hematological malignancies. Our goal is to advance both of these antibodies into the clinic in the second half of next year.\"
Financial terms: Under the terms of the agreement, TG Therapeutics will make an up-front payment as well as make development and sales-based milestone payments and will pay a tiered single digit royalty on net sales.
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