HGS has pioneered the development of highly targeted antibody therapies for cancer based on the TRAIL receptor apoptotic pathway. The Company’s TRAIL receptor antibodies specifically bind to TRAIL receptors 1 or 2, and directly induce the death of cancer cells through apoptosis, or controlled cell death.

HGS-ETR1 (mapatumumab), an antibody to TRAIL receptor 1, is the most advanced of any product in development that targets the TRAIL apoptotic pathway. HGS is currently conducting two randomized Phase 2 clinical trials of HGS-ETR1 – a trial of HGS-ETR1 in combination with bortezomib (Velcade) in patients with advanced multiple myeloma, and a trial of HGS-ETR1 in combination with paclitaxel and carboplatin as first-line therapy in patients with non-small cell lung cancer.

The results of an open-label, dose-escalation Phase 1b trial in patients with advanced solid tumors have demonstrated that HGS-ETR2 (lexatumumab), an antibody to TRAIL receptor 2, was generally safe and well tolerated in combination with four different standard chemotherapy regimens.

HGS believes that the TRAIL pathway offers therapeutic opportunities across a broad range of cancers. In December 2007, the Company acquired exclusive rights from Aegera Therapeutics to develop and commercialize a novel class of small molecules that also enhance apoptosis in cancer cells. These small molecules, known as IAP inhibitors, target a family of proteins that help cancer cells resist apoptosis and start growing again. HGS1029, the lead IAP inhibitor, is expected to enter clinical development early in 2008.

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