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Human Genome Sciences Completes Patient Enrollment in a Phase 2 Clinical Trial of HGS-ETR1 for the Treatment of Colorectal Cancer

Posted on: Wednesday, 23 February 2005, 09:00 CST

ROCKVILLE, Md., Feb. 23 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. announced today that it has completed the enrollment and initial dosing of patients in a Phase 2 clinical trial of HGS-ETR1 (mapatumumab) in patients with advanced colorectal cancer.

(Logo: http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGO )

The Phase 2 clinical trial is an open-label study to evaluate the efficacy, safety and tolerability of HGS-ETR1 in patients with relapsed or refractory colorectal cancer.(1) The Phase 2 study is being conducted in Germany. Patients enrolled in the trial are receiving up to six cycles of treatment in the absence of disease progression, with HGS-ETR1 administered as an intravenous infusion once every fourteen days. The primary objective of the study is to evaluate tumor response. The secondary objectives are to evaluate the safety and tolerability of HGS-ETR1, to determine plasma concentrations of HGS-ETR1 for use in a population pharmacokinetic analysis, and to evaluate other indicators of disease activity, including time to response, duration of response, and progression-free survival.

Professor Dr. Siegfried Seeber, principal investigator and Director, University Clinic for Internal Medicine and Policlinic (Tumor Research), West German Tumor Center, University of Essen, Germany, said, "Combinations of chemotherapeutic agents and, more recently, monoclonal antibodies, have demonstrated clinical benefit for patients with advanced colorectal cancer, but the prognosis for these patients continues to be poor.(2-16) Less than ten percent of the patients who develop metastatic disease survive for five years.(17-20) There is a significant medical need for effective new therapeutic agents. We look forward to continuing the evaluation of HGS-ETR1 throughout the treatment phase of the current study."

Florian Bieber, M.D., Vice President, Drug Development - Europe, said, "The rapid enrollment of the Phase 2 trial of HGS-ETR1 reflects the strong interest within the European oncology community in the ability of our TRAIL receptor antibodies to inhibit or reduce tumor growth in xenograft models of colorectal cancer, to induce significant tumor regression in some models of the disease, and to trigger apoptosis in numerous cancer cell lines, including colorectal cancer."

David C. Stump, M.D., Executive Vice President, Drug Development, said, "We are pleased to have completed the enrollment of our Phase 2 clinical trial of HGS-ETR1 in patients with colorectal cancer. We also have completed the enrollment of our Phase 2 trial of HGS-ETR1 in non-small cell lung cancer, and we continue to enroll patients in our Phase 2 trial in non-Hodgkin's lymphoma.(21-23) We expect to have the results of the three ongoing Phase 2 studies of HGS-ETR1 available in 2005, along with the results of our ongoing Phase 1b studies in combination with chemotherapy. These results will inform our decisions regarding further single agent and chemotherapy combination development of HGS-ETR1 as a treatment for cancer."

Interim results of two ongoing Phase 1 multi-center, open-label, dose- escalation clinical trials of HGS-ETR1 were presented in September 2004 at the 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland.(24-26) The data presented demonstrate the safety and tolerability of HGS-ETR1 in patients with advanced solid tumors or non- Hodgkin's lymphoma, and support further evaluation of HGS-ETR1 in Phase 2 clinical trials, both as a single agent and in combination with chemotherapy. Data were presented on 39 patients treated to date in a Phase 1 study conducted in patients with advanced solid tumors. Interim results of the ongoing study demonstrate that HGS-ETR1 can be administered safely and repetitively to patients with advanced solid malignancies at doses up to and including 10 mg/kg intravenously every 28 days. Some preliminary evidence of biological activity has been observed. Durable stable disease for greater than eight months was observed in one patient with metastatic sarcoma. Durable stable disease was observed for four months in one patient with head- and-neck cancer and in one patient with Ewing's sarcoma; both patients continue on treatment. Data also were presented on 24 patients treated to date in an additional Phase 1 study conducted in patients with advanced solid tumors or non-Hodgkin's lymphoma. Results presented from the ongoing clinical trial demonstrate that HGS-ETR1 is well tolerated with no clearly attributable toxicities to date and that the Maximum Tolerated Dose has not been reached. Stable disease has been observed in eight patients for greater than two cycles. The trial continues to enroll patients.

Human Genome Sciences, using genomic techniques, originally identified the TRAIL Receptor-1 protein as a member of the tumor necrosis factor receptor super-family. The company's own studies, as well as those conducted by others, show that TRAIL Receptor 1 plays a key role in triggering apoptosis, or programmed cell death, in tumors. Human Genome Sciences took the approach of developing human monoclonal antibodies that would bind the receptor and stimulate the TRAIL Receptor-1 protein to trigger apoptosis in cancer cells, in much the same way that the native TRAIL ligand (tumor necrosis factor- related apoptosis-inducing ligand) triggers it, but with the advantage of a longer half-life and an exclusive specificity for TRAIL Receptor 1. Human Genome Sciences' own clinical and preclinical studies, along with published results in the scientific literature, demonstrate that agonistic antibodies to the death domain-containing TRAIL receptors have significant potential to provide novel therapeutic options to patients with a variety of cancer types.(27-43)

The TRAIL Receptor 1 agonistic human monoclonal antibody, HGS-ETR1, was made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology.(44) The drug will be produced in the Human Genome Sciences clinical manufacturing facilities located in Rockville, Maryland. Human Genome Sciences holds the commercial rights to the drug.

Colorectal cancer is the second-leading cause of cancer-related deaths in Western Europe and the United States (after lung cancer). The overall five- year survival of patients with colorectal cancer is approximately fifty percent.

For more information about HGS-ETR1, see http://www.hgsi.com/products/ETR1.html. Health professionals interested in more information about trials involving Human Genome Sciences products are encouraged to inquire via the Contact Us section of the company's web site, http://www.hgsi.com/products/request.html, or by calling (301) 610-5790, extension 3550.

Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based protein and antibody drugs to patients.

HGS and Human Genome Sciences are trademarks of Human Genome Sciences, Inc.

This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences' current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company's unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company's ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company's dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today's date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.

Footnotes:

1. (HGSI Press Release) Human Genome Sciences Initiates a Phase 2

Clinical Trial of HGS-ETR1 in Patients with Colorectal Cancer.

October 13, 2004.

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21. (HGSI Press Release) Human Genome Sciences Advances Anti-Cancer Drug

to Phase 2 Clinical Development. September 8, 2004.

22. (HGSI Press Release) Human Genome Sciences Completes Enrollment in a

Phase 2 Clinical Trial of HGS-ETR1 for the Treatment of Non-Small Cell

Lung Cancer. November 30, 2004.

23. (HGSI Press Release) Human Genome Sciences Begins Dosing of Patients

in a Phase 2 Clinical Trial of HGS-ETR1 in Non-Hodgkin's Lymphoma.

October 13, 2004.

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26. (HGSI Press Release) Human Genome Sciences Reports Results of Ongoing

Phase 1 Clinical Trials of HGS-ETR1 in Patients with Advanced Cancers.

September 29, 2004.

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receptor 4. J Immunol 2001; 166:4891-4898.

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soluble APO2 ligand. J Clin Inv July 1999; 104(2): 155-162.

44. (HGSI Press Release) Cambridge Antibody Technology and Human Genome

Sciences Announce Second Drug Partnership. January 8, 2002.

Photo: http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGOAP Archive: http://photoarchive.ap.org/PRN Photo Desk, photodesk@prnewswire.com

Human Genome Sciences, Inc.

CONTACT: Jerry Parrott, Vice President, Corporate Communications,+1-301-315-2777, or Kate de Santis, Director, Investor Relations,+1-301-251-6003, both of Human Genome Sciences, Inc.

Web site: http://www.hgsi.com/

Company News On-Call: http://www.prnewswire.com/comp/121115.html

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