ROCKVILLE, Maryland – October 1, 2004 – Human Genome Sciences, Inc. (Nasdaq: HGSI) today described the results of preclinical studies presented this week at the 16^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics held in Geneva, Switzerland, September 28-October 1, 2004. Company scientists and collaborators presented the results of preclinical studies of HGS-ETR1, HGS-ETR2, HGS-TR2J, and the TRAIL death receptors, TRAIL-R1 and TRAIL-R2. The conference is organized jointly by the European Organisation for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI) and American Association for Cancer Research (AACR).

A poster presented on September 29, entitled “HGS-TR2J, a Human, Agonistic, TRAIL Receptor-2 Monoclonal Antibody, Induces Apoptosis, Tumor Regression and Growth Inhibition as a Single Agent in Diverse Human Solid Tumor Cell Lines” (Abstract #204)¹, described the results of preclinical studies designed to assess the in vitro and in vivo efficacy of HGS-TR2J in non-small cell lung cancer (NCSLC), ovarian and colon tumor cell lines in cytotoxicity assays and xenograft tumor models. The results of in vitro studies demonstrate that HGS-TR2J binds specifically to TRAIL-R2. Also, a majority of the cell lines in each tumor type expressed high levels of TRAIL-R2 on the cell surface and displayed moderate to significant sensitivity (50-90% cell death) to HGS-TR2J in vitro. In subcutaneous colon carcinoma (COLO205) and NSCLC (H2122) xenograft models, HGS-TR2J induced significant (p<0.0001) and rapid tumor regression (~80% decrease in tumor volume in 4 days) after a single 2.5 mg/kg intravenous dose, and persistent inhibition of tumor growth with continual weekly treatment. In contrast, in NSCLC (H460) and ovarian carcinoma (A2780) xenograft models, HGS-TR2J significantly (p<0.001) inhibited tumor growth, but did not induce tumor regression. The difference in observed in vivo responsiveness did not correlate with in vitro TRAIL-R2 expression. In the colon carcinoma (COLO205) xenograft model, the rapid decrease in tumor volume after HGS-TR2J administration was associated with a dramatic increase in intra-tumor apoptosis within 12 hours of treatment. These data reveal that: (1) HGS-TR2J is specific for human TRAIL-R2 and does not recognize other TRAIL receptor family members. (2) HGS-TR2J induces cell death in a broad range of human tumor cell lines. (3) HGS-TR2J demonstrates significant anti-tumor activity as a single agent in xenograft models of multiple human tumor types. (4) HGS-TR2J treatment in sensitive xenograft models induces rapid and profound tumor regression and/or complete elimination of tumor. (5) HGS-TR2J elicits high-level apoptosis within 12 hours of treatment in solid xenograft tumors.

Human Genome Sciences is currently dosing patients in a Phase 1 clinical trial of HGS-TR2J in patients with advanced solid malignancies.¹ 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. ³ 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.

A poster presented on September 29, entitled “Variable Distribution of TRAIL Receptor 1 in Primary Human Tumor and Normal Tissues” (Abstract #225), described the results of a preclinical study that uses a highly specific immunohistochemical assay to identify specific malignancies that are most likely to express TRAIL-R1. ⁴ Such malignancies could be strong candidate indications for HGS-ETR1. The study, conducted by scientists at Human Genome Sciences in collaboration with scientists from DakoCytomation and Fox Chase Cancer Center, evaluated TRAIL-R1 in human tumor and normal tissue. Of the first 134 malignancies evaluated, a total of 87 tumors (65 percent) showed some degree of TRAIL-R1 specific staining. TRAIL-R1 specific staining was consistently weak or absent in all 17 normal tissues assayed. Tumors of the pancreas, colon and lung were the most likely to have substantial staining for TRAIL-R1. Prostatic carcinomas were least likely to demonstrate TRAIL-R1 staining. The level of TRAIL-R1 protein in the colon was explored further in 26 additional samples representative of typical neoplastic progression. TRAIL-R1 staining distribution and intensity were increased in malignancies of the colon as compared to benign lesions or focal carcinomas in situ.

Human Genome Sciences has begun dosing patients in a Phase 2 clinical trial of HGS-ETR1 in patients with advanced non-small cell lung cancer.⁵ Results of ongoing Phase 1 clinical trials of HGS-ETR1 in advanced solid tumors and non-Hodgkin’s lymphoma were presented at the EORTC-NCI-AACR symposium on September 29, and are the subject of a separate press release.^{6, 7, 8}

A poster presented on October 1, entitled “Effective Combinations of Carboplatin with Low Doses of TRAIL, HGS-ETR1 and HGS-ETR2 in the TRAIL-Sensitive HX62 Human Ovarian Tumour Cell Line” (Abstract #637), described the results of a preclinical study, conducted by Human Genome Sciences’ collaborators at the Institute of Cancer Research (Sutton, UK), which examined the response of ovarian tumor cell lines HX62 and SKOV-3 to combinations of the agonistic antibodies, HGS-ETR1 and HGS ETR2, with carboplatin.⁹ The results presented demonstrate that: HGS-ETR1 and HGS-ETR2 are effective in combination with carboplatin in both the TRAIL-sensitive HX62 and TRAIL-resistant SKOV-3 cell lines, suggesting that they hold promise in combination with platinum-based drugs. Both HGS-ETR1 and HGS-ETR2 sensitize the TRAIL-resistant SKOV-3 ovarian tumor cell line to carboplatin. In the TRAIL-sensitive line, HX62, the combination of HGS-ETR1 with carboplatin was additive in HX62, while the combination of HGS-ETR2 and carboplatin was synergistic.

The HGS-ETR1 and HGS-ETR2 agonistic human monoclonal antibodies, respectively, to TRAIL-R1 and TRAIL-R2 were made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology.¹⁰ Human Genome Sciences holds the commercial rights to both drugs.

David C. Stump, M.D., Executive Vice President, Drug Development, said, “The preclinical data presented at the 16^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics add to the mounting scientific support for our ongoing clinical development of HGS-ETR1, HGS-ETR2 and HGS-TR2J. Each of these antibodies shows promise for potential use in the treatment of solid tumor and other cancers, and we look forward to continuing to explore their potential in clinical studies.”

Human Genome Sciences, using genomic techniques, originally identified the TRAIL Receptor-1 and TRAIL Receptor-2 proteins as members of the tumor necrosis factor receptor super-family. The company’s own studies, as well as those conducted by others, show that both receptors play a key role in triggering apoptosis, or programmed cell death, in tumors.^11-36 Human Genome Sciences took the approach of developing human monoclonal antibodies that would specifically bind the TRAIL Receptor-1 and TRAIL Receptor-2 proteins, respectively, 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 more information about HGS-ETR1, see www.hgsi.com/products/ETR1.html. For more information about HGS-ETR2, see www.hgsi.com/products/ETR2.html. For more information about HGS-TR2J, see www.hgsi.com/products/TR2J.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 (240) 314-4400, 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. R. Humphreys, et al. HGS-TR2J, a human, agonistic, TRAIL Receptor-2 monoclonal antibody, induces apoptosis, tumor regression and growth inhibition as a single agent in diverse human solid tumor cell lines. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Abstract #204.
2. (HGSI Press Release) Human Genome Sciences Initiates Clinical Development of New Drug for the Treatment of Cancer. August 24, 2004.
3. (HGSI Press Release). Human Genome Sciences Announces Joint Development of Antibody for the Treatment of Cancer with Kirin. December 3, 2002.
4. W. Halpern, et al. Variable distribution of TRAIL Receptor 1 in primary human tumor and normal tissues. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Abstract #225.
5. (HGSI Press Release) Human Genome Sciences Advances Anti-Cancer Drug to Phase 2 Clinical Development. September 8, 2004.
6. R.B. Cohen, et al. A phase 1 clinical trial of HGS-ETR1, an agonistic monoclonal antibody to TRAIL-R1, in patients with advanced solid tumors.” 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Oral Presentation.
7. S.J. Hotte, et al. Phase 1 study of a fully human monoclonal antibody to the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) in subjects with advanced solid malignancies or non-Hodgkin’s lymphoma (NHL). 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Abstract #208.
8. (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.
9. B. Krishnan, M.G. Ormerod, S.B. Kaye, A.L. Jackman. Effective combinations of carboplatin with low doses of TRAIL, HGS-ETR1 and HGS-ETR2 in the TRAIL-sensitive HX62 human ovarian tumour cell line. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Abstract #637.
10. (HGSI Press Release) Human Genome Sciences And Cambridge Antibody Technology Commit To Exclusive Development Of Antibody To Trail Receptor-2. May 20, 2002.
11. A. Askenazi. Targeting death and decoy receptors of the tumor necrosis factor superfamily. Nat Revs Cancer 2002; 2:420-430.
12. A. Ashkenazi. Apo-2L/TRAIL in Cytokine Reference. Academic Press, 2000.
13. D.J. Buchsbaum, T. Zhou, W.E. Grizzle, et al. 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. Clin Cancer Research 2003; 9:3731-3741.
14. D. Gillotte, Y. Zhang, C. Poortman, et al. 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. Proceedings from the AACR, 2004; 73:3579.
15. G.V. Georgakis, et al. 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. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #6595.
16. R. Humphreys, et al. 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. 94th AACR Annual Meeting. Abstract #642.
17. R. F. Alderson, et al. TRAIL-R2 mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis inducing ligand receptor 2, induces apoptosis in human tumor cells. 94th AACR Annual Meeting. Abstract #963.
18. Salcedo, Alderson, Basu, et al. TRM-1, a fully human TRAIL-R1 agonistic monoclonal antibody, displays in vitro and in vivo anti-tumor activity. American Association for Cancer Research 93rd Annual Meeting. April 2002. Abstract 4240.
19. Pukac, Kanakaraj, Alderson, et al. 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. American Association for Cancer Research 94th Annual Meeting. July 2003. Abstract 6429.
20. R. Humphreys, et al. TRAIL-R1 and TRAIL-R2 human agonistic monoclonal antibodies display in vitro and in vivo activity on human cancer cells. Society for Biological Therapy, 2002. Oral presentation.
21. A. Chuntharapai, K. Dodge, K. Grimmer, et al. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J Immunol 2001; 166:4891-4898.
22. K. Ichikawa, W. Liu, L. Zhao, et al. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 2001; 7:954-960.
23. A. Younes, M.E. Kadin. Emerging applications for the tumor necrosis factor family of ligands and receptors in cancer therapy. J Clin Oncol. 2003; 21:3526-3534.
24. A. Ashkenazi, R.C. Pai, S. Fong, et al. Safety and anti-tumor activity of recombinant soluble APO2 ligand. Journal of Clinical Investigation. 1999; 104:55-162.
25. G. Pan, et al. The receptor for the cytotoxic ligand TRAIL. Science 1997; 276:111-113.
26. C. Choi, O. Kutsch, J. Pak, et al. Tumor necrosis factor-related apoptosis-inducing ligand induces caspase-dependent interleukin-8 expression and apoptosis in human astroglioma cells. Molecular and Cellular Biology 2002; 22:724-736.
27. B. Gliniak, T. Le. Tumor necrosis factor-related apoptosis-inducing ligand’s antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11. Cancer Research 1999; 59:6153-6158.
28. S.K. Kelley, et al. Preclinical studies to predict the disposition of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand in humans: Characterization of in vivo efficacy, pharmacokinetics, and safety. J Pharmacol Exp Ther. 2001; 299:31-38.
29. N. Mitsiades, S.P. Treon, et al. TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: Therapeutic applications. Blood 2001; 98:795-804.
30. R.M. Pitti, S.A. Marsters, S. Ruppert, et al. Induction of apoptosis by Apo-2 Ligand, a new member of the tumor necrosis factor receptor family. J Biol Chem. 1996; 271:12690-12697.
31. S. Tanaka, K. Sugimachi, K. Shirabe, et al. Expression and antitumor effects of TRAIL in human cholangiocarcinoma. Hepatology. 2000; 32:523-527.
32. M. Nagane, G. Pan, J.J. Weddle, et al. Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo. Cancer Research. 2000; 60:847-853.
33. H. Walczak, R.E. Miller, K. Ariail, et al. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat. Med. 1999; 5:157-163.
34. S.R. Wiley, K. Schooley, P.J. Smolak, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995; 3:673-682.
35. M. Jo, et al. Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nat Med. 2000; 6:564-567.
36. D. Lawrence, Z. Shahrokh, S. Marsters, et al. Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat Med. 2001; 7:383-385.

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