TetraLogic’s research programs focus on discovering drugs that modulate cell death pathways. The Company initially focused on the discovery and development of drugs to treat cancer by modulating apoptosis, a cellular mechanism that regulates programmed cell death. TetraLogic’s second program is focused on programmed necrotic cell death based on the discovery that necrosis, like apoptosis, is a controlled cellular process which can be inhibited by small molecule drugs. The Company is working on a new class of drugs that inhibit necrosis, called Necrostatins that have promise for many clinical indications including cardiovascular, neurological and ophthalmic diseases and injuries.

Smac Mimetic Program

Apoptosis is a highly regulated cellular process found in all multi-cellular organisms involved in tissue homeostasis. Its normal role is to remove abnormal cells enabling them to be replaced by normal, fully functional cells. Disease results when regulation of the apoptosis process breaks down. For example, when the apoptosis pathway is blocked, cells do not die as directed. In cancer, tumor cell development and survival are dependent on the inhibition of apoptosis resulting in uncontrolled cancer formation and progression.

Inhibitor of Apoptosis Proteins (IAPs) are cellular proteins that function in a regulatory role to prevent unintended cell death by apoptosis. Cancer cells frequently over-express IAPs resulting in much higher levels than normal allowing the cancer to survive and progress. TetraLogic scientists have designed drugs called Smac Mimetics that reverse the effects of the IAPs causing the cancer cells to die by apoptosis. Smac Mimetics target Inhibitor of Apoptosis Proteins including XIAP, cIAP-1 and cIAP-2 and ML-IAP and cause apoptotic cell death in a broad range of tumor types. Smac Mimetic drugs will be potentially useful to treat many types of cancer alone and in combination with other therapies. TetraLogic expects to commence clinical development of its lead Smac Mimetic TL32711 during 2009.

Necrostatin Program

Necroptosis is form of regulated programmed cell death via necrosis that has been characterized over the past decade. Necroptosis is distinct from apoptosis as it does not involve key apoptosis regulators such as caspases and has distinct non-apoptotic morphology. Although it occurs under regulated conditions, necroptotic cell death is characterized by the same morphological features as necrotic death. Necrosis occurs in many debilitating conditions such as neurological injuries, neurodegenerative diseases, cardiovascular injuries, major organ failure, pathogenic infections and ophthalmic diseases and injuries.

Necrostatins are a first-in-class family of small molecule compounds that selectively inhibit necrotic cell death. Because Necrostatins block necrotic cell death induced by multiple ligands at a crucial signal transduction pathway checkpoint, they represent a unique mode of action compared to other pharmacological intervention strategies like TNF or Fas inhibitors that target singular cell death stimuli. Necrostatins have shown preclinical efficacy in cardiovascular, neurological and ophthalmic diseases and injuries. TetraLogic expects to commence clinical development of its lead Necrostatin drug candidate during 2010.