CK-301 is a fully human antagonistic monoclonal antibody that binds PD-L1 and blocks its interaction with Programmed cell death protein 1 (“PD-1”). PD-1 and its ligand PD-L1 are checkpoints of immune activation and play a very important role in negative regulation of T-cell effector function and proliferation. Physiological interaction between these molecules inhibits immune activation to prevent autoimmunity and to induce self-tolerance. Many different cancers take advantage of this pathway by expressing PD-L1 and triggering negative signaling in PD-1expressing tumor reactive T-cells thus blocking anti-tumor T-cell immune response.
Numerous preclinical and clinical studies have demonstrated that antibodies blocking interaction of PD-1 with its ligands or those blocking interaction of PD-L1 alone with PD-1 can augment anti-tumor T-cell responses and lead to complete and lasting tumor eradication in a certain proportion of patients. Confirmed overall response rate (“ORR”) in the U.S. Food and Drug Administration (“FDA”) labels for the approved PD-1 blocking antibodies was cited in the 20-30% range based on clinical trials in patients with metastatic melanoma. Potent therapeutic anti-tumor responses due to blocking of PD-1/PD-L1 interaction has been demonstrated in patients with melanoma, renal cell carcinoma (“RCC”) and non-small cell lung carcinoma (“NSCLC”).
We plan to develop an anti-PD-L1 antibody for oncology indications, including, but not limited to, the treatment of patients with NSCLC and RCC. In March of 2015, we entered into a partnership agreement to co-develop an anti-PD-L1 antibody for hematological oncological indications with TG Therapeutics, Inc. (“TGTX”). We believe that an anti-PD-L1 antibody has the potential to be effective in many oncological indications as a mono therapy or in combination with other anti-tumor immune response potentiating compounds and other targeted therapies.
We licensed the exclusive worldwide rights to anti-PD-L1 antibodies from Dana-Farber in March 2015. We dosed the first patient in a phase 1 study of CK-301 in October 2017.