Human Genome Sciences, Inc. acquired exclusive worldwide rights (excluding Japan) to develop and commercialise Aegera Therapeutics' AEG 40826, a key small molecule inhibitor used to treat cancer.

Under the terms of the agreement, Human Genome Sciences (HGS) has paid Aegera an upfront license fee of $15 million and has made an equity investment of C$5 million. Aegera will be entitled to receive up to $295 million in future development and commercial milestone payments, including a $5 million milestone payment upon FDA clearance of an IND.

Aegera will receive double-digit royalties on net sales in the HGS territory. In North America, Aegera will have the option to co-promote, under which it will share certain expenses and profits (30 per cent) in lieu of its royalties. Aegera retains the non-oncology rights to its IAP inhibitors that are not selected for development under this agreement.

In addition to the AEG 40826 acquisition, HGS also bagged the rights of certain related backup compounds to be chosen during three-year research collaboration.

AEG40826 is a potent small-molecule inhibitor of multiple IAP (inhibitor of apoptosis) protein family members that is expected to begin oncology clinical trials in early 2008.

"Today's announcement underscores HGS's commitment to develop novel targeted therapies for the treatment of cancer," said H. Thomas Watkins, president and chief executive officer, HGS. "Our company has pioneered development of antibody therapies based on the TRAIL receptor apoptotic pathway, and we will now have the opportunity to work collaboratively with Aegera Therapeutics to develop and commercialise exciting small-molecule drugs that also enhance apoptosis in cancer cells. We look forward to developing our TRAIL receptor antibodies and IAP inhibitors in combination with one another and in combination with other therapeutic agents. We believe this agreement substantially enhances the value of our promising oncology franchise."

Preclinical studies of AEG 40826 in combination with the HGS TRAIL receptor antibodies have demonstrated dramatic synergistic activity against a number of cancer types, including prostate, breast, esophageal, colorectal and non-small cell lung cancer. Preclinical studies also show that AEG 40826 has significant anti-tumour activity alone and in combination with other anti-cancer agents in a broad range of cancers.

"We carefully evaluated potential partners for our small molecule IAP oncology franchise and are very excited to announce our collaboration with Human Genome Sciences today," said Dr. Michael Berendt, president and chief executive officer, Aegera Therapeutics. "We believe that the combination of our extensive knowledge of the control of apoptotic pathways with HGS's unparalleled understanding of the development of targeted therapeutics, their strong research and development teams and their leadership in the clinical development of TRAIL receptor human monoclonal antibodies will significantly enhance the potential for the rapid and successful development of AEG40826 and follow-on compounds for multiple oncology indications."

Activation of apoptosis (programmed cell death) in cancer cells is a key goal of cancer treatment. The proteins in the IAP (inhibitor of apoptosis) family are important regulators of apoptosis in cancer cells. A growing body of evidence indicates that cancer cells may avoid apoptosis by the sustained over-expression of one or more members of the IAP family. Decreased IAP expression has been shown to sensitise a number of tumour types to a wide variety of treatment modalities.

AEG40826 is a member of a new class of designed small molecules that directly, or in combination with other anti-cancer treatments, cause the death of tumour cells through antagonism of IAP function. Preclinical studies clearly demonstrate that AEG40826 potently stimulates apoptosis of human tumour cells in vitro and in vivo. Consistent with its mechanism of action, AEG40826 causes a rapid loss of IAP proteins in human tumour xenografts.

Aegera T herapeutics is a clinical-stage biotechnology company focused on developing drugs that control apoptosis to address major unmet medical needs. In addition to AEG40826, Aegera has three clinical stage/IND track programs in development for oncology and neuropathic pain.

The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs. The HGS clinical development pipeline includes novel drugs to treat hepatitis C, lupus, anthrax disease, cancer and other immune-mediated diseases.