Aegera Therapeutics announced the initiation of four new clinical oncology studies for AEG35156, a second-generation anti-sense therapeutic targeting the X-Linked Inhibitor of Apoptosis (XIAP), a key member of the Inhibitor of Apoptosis protein (IAP) family.

Following completion of several phase I trials, Aegera has initiated an open-label phase II study in acute myeloid leukaemia (AML) with AEG35156 given in combination with ara-C and idarubicin. This study is being performed at six sites across North America including MD Anderson (Texas), Princess Margaret Hospital (Ontario), Johns Hopkins Medical Center (Maryland), North-western Memorial Hospital (Illinois), University of California in Los Angeles (California) and Maisonneuve-Rosemont Hospital (Quebec), said a company press release.

In addition, three other multicenter open-label phase I/II studies have been initiated with AEG35156 in pancreatic cancer, advanced breast cancer and advanced non-small cell lung cancer. In these studies, AEG35156 will be combined with current standard of care chemotherapeutics. The phase I arm of these trials will determine the recommended dose of AEG35156 to be used in combination with the respective chemotherapeutic agents. The phase II arm of each study will evaluate the effects of combining AEG35156 with chemotherapy on the expected response rate in these patient populations.

"The mechanism of action of AEG35156 strongly suggests that it will be effective in combination with chemotherapeutics across a wide spectrum of cancer types. Our initial phase II studies in AML, pancreatic, breast, and non-small cell lung cancer were chosen based on the preclinical data, our understanding of the relevance of the XIAP target, clinical correlates and the considerable medical need for improved treatment in these cancer types," said, Dr. Michael Berendt, chief executive officer, Aegera.

"Early clinical evidence indicates that AEG35156 reduces XIAP mRNA and protein levels in some solid tumours and hematologic cancers. The biological activity of AEG35156, if it is borne out in these trials, should make cancer cells more susceptible to standard chemotherapeutics," said, Dr. Bruce Chabner, clinical advisory board member, Aegera.

Cancer cells acquire multiple mutations that disable their normal response to apoptotic triggers. AEG35156, a second-generation anti-sense, which targets XIAP, is designed to lower the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy, without harming healthy cells. Aegera's published data with AEG35156, both in vitro and in vivo, strongly supports this hypothesis, and validates XIAP as a novel drug target for the development of anti-cancer therapeutics. AEG35156 has demonstrated strong efficacy in models of lung, breast, ovarian, colorectal and prostate cancers, the company said.

Aegera Therapeutics is a clinical stage biotechnology company focused on developing drugs that control apoptosis to address major unmet medical needs. Multiple programs are in development to induce apoptosis to kill cancer cells and to prevent apoptosis to save injured neuronal cells:

AEG35156 targets the key anti-apoptotic protein XIAP, and is currently in multiple human clinical trials for the treatment of solid tumours and leukaemia. LS104 is a novel, non-ATP competitive, small molecule tyrosine kinase inhibitor targeting therapeutically significant kinases including JAK2 and Bcr-Abl, the company statement said. AEG40826 is a potent small molecule that neutralizes the activity of key Inhibitor of Apoptosis Proteins (IAPs), and has begun definitive IND-enabling preclinical toxicology studies as an anti-cancer therapeutic.