Phase 1b/2a Five-Arm Combination Cancer Study Initiated for Novel Smac Mimetic TL32711
MALVERN, Pa., Jan. 5, 2011 /PRNewswire/ -- TetraLogic Pharmaceuticals, a biopharmaceutical company developing novel small molecule drugs to treat cancer, today announced that is has closed the $23 million second tranche of a Series C financing completed in October 2010.
The company will use the funds to advance the clinical development of its lead Smac mimetic drug candidate, TL32711. TetraLogic recently completed dosing in the first cohort of a Phase 1b/2a five-arm combination clinical study. The Phase 1b portion of the study is an open-label, non-randomized, dose-escalation study investigating the safety and tolerability of TL32711 in combination with standard-of-care chemotherapies in patients with advanced or metastatic solid tumors. Chemotherapeutics in the five-arm Phase 1b study include carboplatin/paclitaxel, irinotecan, docetaxel, gemcitabine and DOXIL®. The Phase 2a portion of the study will focus on indications that are potential candidates for advancement to registration.
"In targeting the fundamental mechanisms of cancer cell survival and resistance, Smac mimetics have become an important and promising field of research for cancer therapy development," said John Gill, TetraLogic's president and chief executive officer. "Our most advanced Smac mimetic, TL32711, may prove to be an efficacious and safe compound for treating a variety of solid tumor and hematological cancers, and its rapid clinical development continues to position TetraLogic as a leader in the field."
The Series C financing was led by Clarus Ventures and included Hatteras Venture Partners and Pfizer Ventures, along with existing investors HealthCare Ventures, Latterell Venture Partners, Novitas Capital, Quaker BioVentures, the Vertical Group, and Amgen Ventures. Also participating in the financing were Andrew Pecora, TetraLogic's chairman of the board and chief innovations officer, professor and vice president of cancer services at the John Theurer Cancer Center at Hackensack University Medical Center, and George McLendon, a founding scientist, chairman of TetraLogic's scientific advisory board and provost of Rice University.
About Apoptosis and Smac Mimetics
Apoptosis, a process of programmed cell death, is the primary way that cancer cells are destroyed by standard therapies and also by the body's biological responses to cancer. Apoptosis can be activated by a number of internal (intrinsic pathway) and external (extrinsic pathway) signals including chemotherapy, oxidative stress, irradiation and death receptor ligand binding such as tumor necrosis factor alpha (TNF alpha) and TNF-related apoptosis-inducing ligand (TRAIL). The inhibitor of apoptosis proteins (IAPs) block apoptosis by inhibiting caspase activation at the TNF receptor level and by directly binding to and inhibiting executioner caspases.
Smac (second mitochondria-derived activator of caspases) is the endogenous inhibitor of IAPs that antagonizes the activity of IAPs by inducing their degradation and neutralizing their inhibitory effect on caspases. In cancer, there is an imbalance between IAPs and Smac resulting in elevated levels of IAPs, which influences cancer survival, progression and resistance to therapy. Smac mimetics are small molecule drugs designed to mimic the action of Smac and correct the cancer imbalance. Smac mimetics bind to IAPs and block their function, thereby restoring the apoptosis pathway. The central role between Smac and IAPs in cancer cell death renders Smac mimetics a promising new class of therapeutics that are relevant to treating all types of cancer by targeting fundamental mechanisms of cancer cell survival and resistance. Smac mimetics have been shown to neutralize IAPs in preclinical studies, and thus, overcome resistance and enable cancer cell apoptosis.
TL32711 is a small molecule peptidomimetic of Smac (an endogenous regulator of apoptotic cell death) that selectively antagonizes multiple IAPs. TL32711 has demonstrated preclinical anti-tumor activity that supports its clinical development for solid tumor and hematological malignancies as a monotherapy and in combination with other anti-cancer therapies.
In December 2009, TetraLogic commenced a Phase 1a/2a single agent study in patients with solid tumors and lymphomas that are refractory to standard therapies.
About TetraLogic Pharmaceuticals
TetraLogic Pharmaceuticals is a privately held biopharmaceutical company that discovers and develops small molecule drugs that modulate programmed cell death pathways to treat debilitating diseases and conditions. The company's most advanced Smac mimetics neutralize selected IAPs to treat cancer. Earlier programs are focused on discovering and developing Smac mimetics to treat certain autoimmune and inflammation related diseases and conditions. For additional information, please refer to the company's Web site at www.tetralogicpharma.com.