ROCKVILLE, Maryland – September 8, 2004 – Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that it has begun dosing patients in a Phase 2 clinical trial of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL Receptor 1) in patients with advanced non-small cell lung cancer.

The Phase 2 clinical trial is a multi-center, open-label, single-arm study to evaluate the efficacy, safety and tolerability of HGS-ETR1 in patients with relapsed or refractory non-small cell lung cancer. The Phase 2 clinical trial will be conducted in the United States, and will enroll a maximum of thirty patients. Each patient will receive four 10 mg/kg doses of HGS-ETR1 administered as an intravenous infusion 21 days apart. The primary objective of the study is to evaluate tumor response. The secondary objectives are to evaluate the safety and tolerability of HGS-ETR1, and to determine plasma concentrations of HGS-ETR1 for use in a population pharmacokinetic analysis. Disease response will be assessed using the RECIST Criteria (Response Evaluation Criteria in Solid Tumors), which were established in 2000 to codify objective means for evaluating changing disease status and the efficacy of drugs in the treatment of solid tumors.¹ The Phase 2 study of HGS-ETR1 in patients with non-small cell lung cancer is the first in a series of Phase 2 clinical trials of HGS-ETR1 through which Human Genome Sciences plans to evaluate the drug’s potential for use in the treatment of specific cancers.

Human Genome Sciences also announced that it has begun to dose patients in an open-label, dose-escalation Phase 1b clinical trial of HGS-ETR1 to evaluate its safety and tolerability in combination with paclitaxel and carboplatin in patients with advanced solid malignancies.

F. Anthony Greco, M.D., a clinical investigator and Medical Director of The Sarah Cannon Cancer Center, Nashville, said, “It is expected that more than 173,000 new cases and more than 160,000 deaths of lung cancer will occur in the United States in 2004.² It is the leading cause of cancer death in this country in both men and women. Non-small cell lung cancers account for approximately 75-80 percent of all lung cancers.² Less than half of newly diagnosed patients are candidates for surgery. The majority of patients present with incurable locally advanced or metastatic disease.³ Non-small cell lung cancer represents a significant medical need, for which further therapeutic advances will depend on the development of new agents directed at newly defined targets. This reality underlies the current high level of interest in the ability of TRAIL receptor antibodies to trigger apoptosis in numerous cancer cell lines, including non-small cell lung cancer. We look forward to exploring the potential of HGS-ETR1 in Phase 2 clinical trials in patients with this deadly disease.”

David C. Stump, M.D., Executive Vice President, Drug Development, said, “Based on strong preclinical evidence and the encouraging interim clinical results available to date from our ongoing Phase 1 clinical trials, we are pleased to advance HGS-ETR1 to a Phase 2 clinical trial in patients with relapsed or refractory non-small cell lung cancer. We plan in 2004 to advance HGS-ETR1 to additional Phase 2 clinical trials, and we also are initiating Phase 1b clinical studies of HGS-ETR1 in combination with chemotherapy. These are important steps forward as we continue to elucidate the potential role of HGS-ETR1 in the treatment of a number of solid tumor and other malignancies.”

Craig A. Rosen, Ph.D., President, Research and Development, said, “Our own preclinical research, along with published results in the scientific literature, demonstrates 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.^4-17 Our own in vitro and in vivo preclinical studies show that HGS-ETR1 inhibits or reduces tumor growth in xenograft models of non-small cell lung cancer, and can induce significant tumor regression in some models of the disease.^{9-11, 14-16} Our studies also show that the activity of HGS-ETR1 in such models may be increased by co-treatment with chemotherapeutic agents, including taxane and platinum-based agents.^6-8 One of the key milestones set by Human Genome Sciences at the beginning of this year was the advancement of HGS-ETR1 to Phase 2 clinical trials. We are pleased to have achieved that milestone, and look forward to the continuing clinical development of HGS-ETR1 for the treatment of cancer.”

Interim results of two ongoing Phase 1 multi-center, open-label, dose-escalation clinical trials of HGS-ETR1 were presented at the June 2004 Annual Meeting of the American Society of Clinical Oncology (ASCO).^18-20 The data presented at ASCO 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. In a Phase 1 study conducted in patients with advanced solid tumors, thirty-three of thirty-seven patients treated to date had received prior chemotherapy. The median number of treatment regimens previously experienced was two, and ranged as high as nine. 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. No evidence of drug-related hematologic or hepatic toxicity has been observed at the doses administered to date. The Maximum Tolerated Dose (MTD) has not been reached, and accrual in the trial continues. Plasma concentrations were observed to be in a range associated with preclinical evidence of biological activity. Durable stable disease for greater than six months was observed in one patient with metastatic sarcoma.^{18, 20} In a second Phase 1 study conducted in patients with advanced solid tumors or non-Hodgkin’s lymphoma, all twenty of the patients treated to date were admitted to the trial with relapsed or refractory disease, and had received prior anti-cancer treatments (chemotherapy, radiotherapy, or hormone therapy). Results presented from the ongoing clinical trial demonstrate that HGS-ETR1 is well tolerated with no clearly attributable toxicities and that the MTD has not been reached. Stable disease has been observed in five patients. The trial continues to enroll patients.^19-20

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. The TRAIL Receptor 1 agonistic human monoclonal antibody, HGS-ETR1, was made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology.²¹ 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.

For more information about HGS-ETR1, see www.hgsi.com/products/ETR1.html. Health professionals interested in more information about trials involving HGSI products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, 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.

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Footnotes:
1. New guidelines to evaluate the response to treatment in solid tumors. JNCI 2000; 92:205-216.
2. Cancer Statistics, 2004. Jemal A, Tiwari RC, Murray T, et al. Cancer 2004; 54(1):8-29.
3. Current Status and Future Directions in Advanced Non-Small Cell Lung Cancer. Lara P, Lau DHM, Davies A, et al. Oncology Special Edition 2002; 4:129-135.
4. Targeting death and decoy receptors of the tumor necrosis factor superfamily. Ashkenazi A. Nat Revs Cancer 2002; 2:420-430.
5. Apo-2L/TRAIL in Cytokine Reference. Ashkenazi A. Academic Press 2000.
6. Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model. Buchsbaum DJ, Zhou T, Grizzle WE, et al. Clin Cancer Research 2003; 9:3731-3741.
7. Human agonistic anti-TRAIL receptor antibodies, HGS-ETR1 and HGS-ETR2, induce apoptosis in ovarian tumor lines and their activity is enhanced by taxol and carboplatin. Gillotte D, Zhang Y, Poortman C, et al. Proceedings from the AACR 2004; 73:3579.
8. Selective Agonistic Monoclonal Antibodies to the TRAIL Receptors R1 and R2 Induce Cell Death and Potentiate the Effect of Chemotherapy and Bortezomib in Primary and Cultured Lymphoma Cells. G.V. Georgakis, et al. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #6595.
9. TRAIL R2-mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis inducing ligand receptor 2, affects tumor growth and induces apoptosis in human tumor xenograft models in vivo. Robin C. Humphreys, Ralph F. Alderson, Eliel Bayever, Kevin Connolly, Gil H. Choi, Norma Lynn Fox, Gilles Gallant, Krzystof J. Grzegorzewski, Viktor Roschke, Theodora W. Salcedo, Jing Zhang, Junli Zhang, Vivian R. Albert. 94th AACR Annual Meeting. Abstract 642.
10. TRAIL-R2 mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis inducing ligand receptor 2, induces apoptosis in human tumor cells. Ralph F. Alderson, Charles E. Birse, Kevin Connolly, Gil H. Choi, Norma Lynn Fox, Gilles Gallant, Ina Han, Robin C. Humphreys, Ron Johnson, Palanisamy Kanakaraj, Vikram Patel, Oxana Pickeral, Laurie Pukac, Viktor Roschke, Theodora Salcedo, Tara Shah, Junli Zhang, Vivian R. Albert. 94th AACR Annual Meeting. Abstract 963.
11. TRM-1, a fully human TRAIL-R1 agonistic monoclonal antibody, displays in vitro and in vivo anti-tumor activity. Salcedo, Alderson, Basu, et al. American Association for Cancer Research 93rd Annual Meeting. April 2002, Abstract 4240.
12. TRAIL-R1 mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 1, induces apoptosis in human tumor cells in vitro and in vivo. Pukac, Kanakaraj, Alderson, et al. American Association for Cancer Research 94th Annual Meeting. July 2003, Abstract 6429.
13. TRAIL-R1 and TRAIL-R2 Human Agonistic Monoclonal Antibodies Display In Vitro and In Vivo Activity on Human Cancer Cells. Humphreys R, et al. Society for Biological Therapy 2002; oral presentation.
14. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. Chuntharapai A, Dodge K, Grimmer K, et al. J Immunol 2001; 166:4891-4898.
15. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Ichikawa K, Liu W, Zhao L, et al. Nat Med 2001; 7:954-960.
16. TRM-1, a fully human TRAIL-R1 agonistic monoclonal antibody, displays in vitro and in vivo anti-tumor activity. Salcedo, Alderson, Basu, et al. American Association for Cancer Research 93rd Annual Meeting. April 2002, Abstract 4240.
17. Emerging applications for the tumor necrosis factor family of ligands and receptors in cancer therapy. Younes A, Kadin ME. J Clin Oncol 2003;21:3526-3534.
18. A Phase 1 and Pharmacokinetic Study of HGS-ETR1, A Fully Human Monoclonal Antibody to TRAIL-R1 (TRM-1), in Patients with Advanced Solid Tumors. A.W. Tolcher, et al. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #3060.
19. Phase 1 Study of a Fully Human Monoclonal Antibody to the Tumor Necrosis Factor-Related Apoptosis-Inducting Ligand Death Receptor 4 (TRAIL-R1) in Subjects with Advanced Solid Malignancies or Non-Hodgkin’s Lymphoma. L.H. Le, et al. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #2533.
20. (HGSI Press Release) Human Genome Sciences Reports Results of Phase 1 Clinical Trials of HGS-ETR1 (TRAIL-R1 mAb) in Patients with Advanced Cancers. June 7, 2004.
21. (HGSI Press Release) Cambridge Antibody Technology and Human Genome Sciences Announce Second Drug Partnership. January 8, 2002.

CONTACTS:
David C. Stump, M.D.
Executive Vice President, Drug Development
240/314-4400
Jerry Parrott
Vice President, Corporate Communications
301/315-2777
Kate de Santis
Director, Investor Relations
301/251-6003