Phase 1 clinical trial of new anticancer drug from Human Genome Sciences

Human Genome Sciences has begun dosing patients in a Phase 1 clinical trial of HGS-TR2J, a novel agonistic human monoclonal antibody to TRAIL Receptor 2, in patients with advanced solid malignancies.

HGS-TR2J arises from a license agreement entered into at the end of 2002, under which Human Genome Sciences and the Pharmaceutical Division of Kirin Brewery Company, Ltd., agreed to collaborate on the development and commercialization of antibodies to TRAIL Receptor 2.1 Under the agreement, Kirin will develop and commercialize any resulting drug in Japan and Asia/Australasia, and Human Genome Sciences will develop and commercialize any resulting drug in North America, Europe , and the rest of the world.

The Phase 1 clinical trial of HGS-TR2J is an open-label dose-escalation study. The primary objectives of the clinical trial are to assess safety and tolerability. Pharmacokinetics and disease response also will be evaluated. The trial will be conducted in Canada, and will enroll a maximum of forty-eight patients with relapsed or refractory advanced solid malignancies who have failed standard therapies and for whom no curative option exists, or who have refused all other therapies.

Preclinical studies will be presented at several international cancer meetings this fall, which demonstrate that HGS-TR2J binds TRAIL Receptor 2 with high affinity, induces apoptosis and has anti-tumor activity, both as a single agent and in combination with chemotherapy. HGS-TR2J mimics the activity of native TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and, thus, is considered an agonistic antibody. Numerous nonclinical studies have shown that cell lines derived from a broad array of solid and hematological human tumors, including lung, colon, breast, multiple myeloma, prostate and pancreas, are sensitive to killing by apoptosis (programmed cell death) induced by native TRAIL or by agonistic antibodies to TRAIL Receptors 1 and 2.2-24 The results of in vitro and in vivo preclinical studies providing support for initiating clinical development of HGS-TR2J will be presented at the 16th EORTC-NCI-AACR Symposium on “Molecular Targets and Cancer Therapeutics” (Geneva, September 28-October 1, 2004)25, 26, and the 29th European Society of Medical Oncology Congress (October 29-November 2, 2004).27

Hal Hirte, M.D., Head, Medical Oncology and Systemic Therapy Program, Juravinski Cancer Centre, and Associate Professor, Department of Medicine, McMaster University (Hamilton, Ontario), said, “The ability of TRAIL and TRAIL receptor agonistic antibodies to trigger apoptosis in numerous cancer cell lines has been widely reported. HGS-TR2J is an agonistic antibody to TRAIL Receptor 2, and may offer certain therapeutic advantages in comparison to native TRAIL, due to its significantly longer circulating half-life and its exclusive specificity to TRAIL receptor 2. We look forward to exploring its potential in this initial clinical trial in cancer patients.”

Gilles Gallant, B. Pharm., Ph.D., Vice President, Clinical Oncology, said, “The results of preclinical studies to date demonstrate that agonistic TRAIL receptor antibodies, such as HGS-TR2J, are able to trigger cancer cell death through apoptosis in a number of tumor types.15-23 We believe that HGS-TR2J has significant potential for the treatment of a broad range of solid malignancies, either as a single agent or in combination with chemotherapy, and we are pleased to initiate its clinical development.”

Craig A. Rosen, Ph.D., President, Research and Development, said, “We are very pleased with the progress of our collaboration with Kirin. Our own preclinical studies, as well as those conducted by others, provide mounting evidence that agonistic antibodies to the death domain-containing TRAIL receptors have the potential to provide treatment options to patients with a broad range of tumor types. Our collaboration with Kirin affords us the opportunity to study the Kirin antibodies to TRAIL Receptor 2 alongside our own antibodies and to determine the optimal drug candidate to advance through clinical trials. Early this year, Human Genome Sciences set as a milestone the goal of entering 1-2 new drugs into clinical development in 2004. Entering HGS-TR2J into Phase 1 helps meet that milestone. As we continue to advance our clinical development program, we expect to maintain our priority focus on oncology and immunology/infectious disease.”

Human Genome Sciences originally identified the TRAIL Receptor 2 protein as a member of the tumor necrosis factor family of proteins. TRAIL Receptor 2 often is referred to as a “death receptor” because of its ability to cause apoptosis in tumor cells when triggered by the natural ligand TRAIL. HGS-TR2J was made in a collaboration with the Pharmaceutical Division of Kirin Brewery Company, Ltd. HGS-TR2J will be produced in the Human Genome Sciences clinical manufacturing facility located in Rockville, Maryland.