TetraLogic Pharmaceuticals Corporation, a clinical-stage biopharmaceutical company focused on discovering and developing novel small molecule therapeutics in oncology and infectious diseases, and Merck, known as MSD outside the United States and Canada, have entered into an oncology clinical study collaboration.
The companies will collaborate on a phase 1 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 tumours. 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 (TL32711) is a potent, 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.
"We are very excited to work with Merck to evaluate birinapant in combination with Keytruda," said J. Kevin Buchi , president and chief executive officer of TetraLogic. "Both molecules are designed to help the body's immune system better attack cancer cells, and we think the combination could be very promising."
"We are establishing a broad base of clinical evidence with our anti -PD-1 therapy, Keytruda, as monotherapy across different types of cancer," said Dr. Eric Rubin, vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories. "We believe there is great potential to advance our clinical program and the field of immuno -oncology research through strategic collaborations and synergistic combinations, such as with Keytruda and birinapant."
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 tumours. 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.
Cancer and chronically infected cells are able to evade a critical mechanism by which the immune system normally kills abnormal or genetically modified cells. They do this by upregulating the Inhibitors of Apoptosis (IAP) Proteins. Birinapant (TL32711) is a potent, 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. Birinapant has been studied in over 350 patients, and is currently in phase 1 and phase 2 trials for Myelodysplastic Syndrome (MDS), Ovarian Cancer and Hepatitis B.
Keytruda (pembrolizumab) 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-tumour immune response.
Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumour response rate and durability of response. An improvement in survival or disease -related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merck is advancing a broad and fast -growing clinical development program for Keytruda with more than 85 clinical trials -across more than 30 tumour types and over 14,000 patients-both as a monotherapy and in combination with other therapies.