TetraLogic Pharmaceuticals Corporation, a clinical-stage biopharmaceutical company focused on discovering and developing small-molecule therapeutics in oncology and infectious diseases, and Merck & Co. Inc. have entered into an oncology clinical study collaboration. The companies will collaborate on a Phase I study to evaluate the safety and efficacy of birinapant, TetraLogic's SMAC-mimetic, in combination with Keytruda (pembrolizumab), Merck's anti-PD-1 therapy, in patients with relapsed or refractory solid tumors. The study is expected to begin in late 2015.

Keytruda and birinapant target different elements of cancer's block against the immune system. TetraLogic's birinapant is a bivalent SMAC-mimetic that binds with differential affinity to multiple members of the IAP family in order to re-establish the immune system's ability to kill abnormal cells via an extracellular TNF signal. Merck's Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. The proposed collaboration is based on preclinical data that suggest SMAC-mimetics have the potential to enhance existing immuno-oncology agents, such as Keytruda.

Under the terms of the agreement, TetraLogic and Merck, through subsidiaries, will collaborate on an initial Phase 1 dose-escalation study of birinapant in combination with Keytruda in patients with relapsed or refractory solid tumors. TetraLogic will sponsor and fund the study, and Merck will provide Keytruda. The companies have formed a Joint Development Committee to collaboratively oversee the conduct of the study. Results from the study will be used to determine the path for further clinical development of the combination.

Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. The drug is indicated in the United States for treating unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

Source: Merck & Co.