MALVERN, Pa., March 27, 2014 (GLOBE NEWSWIRE) -- TetraLogic Pharmaceuticals Corporation (Nasdaq:TLOG) today announced that data from its novel SMAC-Mimetic program will be presented during presentations at the American Association for Cancer Research (AACR) Annual Meeting being held April 5-9, 2014 at the San Diego Convention Center in San Diego, California.
Tetralogic is currently testing its lead SMAC-Mimetic, birinapant, in Phase 1 and Phase 2 clinical trials for hematological malignancies and solid tumors. The second mitochondria-derived activator of caspases (SMAC) exerts its pro-apoptotic activity by antagonizing multiple members of the inhibitor of apoptosis (IAP) protein family, which are molecular targets that have been implicated in various cancers.
Birinapant has been shown to promote apoptosis in cancer cells through the formation of a caspase-8/RIPK1 complex and induction of autocrine tumor necrosis factor (TNF). Data presented indicate that autocrine TNF production induced by birinapant is triggered by the activation of the caspase-8/RIPK1/p38MAPK axis and may be regulated by cFLIP isoforms.
Both SMAC-Mimetics (which are bivalent) and monovalent IAP-inhibitors are being developed for cancer therapy. Owing to the structural differences between these two classes of therapies, the biochemical activity of birinapant was compared and contrasted with several monovalent IAP-inhibitors, and in that comparison, birinapant showed substantial differences from monovalent IAP-inhibitors in degrading cIAP1 and cIAP2 associated with TNF receptor-associated factor 2 (TRAF2).
"These data expand our understanding at the molecular level of birinapant's unique mechanism of action of establishing apoptosis in cancer cells," said C. Glenn Begley, Chief Scientific Officer of TetraLogic. "As the only SMAC-Mimetic in the clinic, birinapant is a completely novel therapeutic approach to cancer therapy."
The schedule for the TetraLogic oral and poster presentations is as follows:
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Date & Time: Saturday, April 5, 2014 at 8:15 AM - 8:45 AM
Educational Session ED34: From Chemistry to the Clinic: Pathways for Drug Discovery and Development, Part 1 – Targeting Protein-Protein Interactions.
Presenter: Stephen M. Condon, TetraLogic Pharmaceuticals
Presentation Title: Discovery and Clinical Development of a Smac-mimetic (IAP Inhibitor)
Location: Room 29, San Diego Conference Center
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Session Date and Time: Monday Apr 7, 2014 8:00 AM - 12:00 PM
Session ID: Experimental and Molecular Therapeutics 14
Abstract Number: 1806
Title: Birinapant, a bivalent SMAC-mimetic, promotes efficient cellular IAP E3 ligase activity and formation of a pro-apoptotic RIPK1:caspase-8 complex while monovalent IAP inhibitors are less efficient - implications for therapeutic utility
Authors: Yasuhiro Mitsuuchi, Christopher A. Benetatos, Thomas Haimowitz, Yijun Deng, Angeline C. Mufalli, Martin E. Seipel, Jennifer M. Burns, Gurpreet Singh Kapoor, C. Glenn Begley, and Stephen M. Condon
Location: Hall A-E, Poster Section 33
Poster Board Number:19
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Session Date and Time: Monday Apr 7, 2014 1:00 PM - 5:00 PM
Session ID: Molecular and Cellular Biology 28
Abstract Number: 2278
Title: The SMAC-mimetic birinapant regulates autocrine TNF production by caspase-8:RIPK1 complex via p38MAPK pathway
Authors: Gurpreet S. Kapoor, Christopher A. Benetatos, Yasuhiro Mitsuuchi, Eric M. Neiman, Guangyao Yu, Mark A. McKinlay, John Silke, Stephen M. Condon, and Srinivas K. Chunduru
Location: Hall A-E, Poster Section 17
Poster Board Number:15
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Date & Time: Monday, April 7, 2014, 3:25 PM - 3:45 PM
Special Symposium: Data Reproducibility in Cancer Research: Can You Believe Everything You Read?
Presentation Title: Raising the standards for biomedical research
Presenter: C. Glenn Begley, TetraLogic Pharmaceuticals
Location: Room 8, San Diego Conference Center
About TetraLogic
TetraLogic is a clinical-stage biopharmaceutical company focused on discovering and developing novel small molecule therapeutics that mimic the Second Mitochondrial Activator of Caspases, or SMAC-mimetics, and are designed to cause or enable abnormal cells that are resistant to the body's immune system to self-destruct. Birinapant, our clinical-stage product candidate, is currently being tested in Phase 1 and Phase 2 clinical trials for hematological malignancies and solid tumors.