ROCKVILLE, Maryland – November 2, 2004 – Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced the results of preclinical studies of HGS-TR2J (TRAIL-R2 mAb) and the TRAIL death receptor, TRAIL Receptor 2. The results were presented at the 29th Congress of the European Society for Medical Oncology (ESMO) held in Vienna, Austria, October 29-November 2, 2004.

A poster presented on October 30, entitled “TRAIL-R2 Protein Expression in Normal and Tumor Tissues” (Abstract # 83), described the results of a preclinical study that uses a highly specific immunohistochemical assay to identify malignancies that are most likely to express TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) Receptor 2. ¹ Such malignancies could be strong candidate indications for HGS-ETR2 or HGS-TR2J, both of which are agonistic human monoclonal antibodies to TRAIL Receptor 2. The study evaluated TRAIL-R2 in human tumor and normal tissue. A total of 294 tissue samples were evaluated (252 tumors and 42 normals). Tumors evaluated included at least ten samples each of colon, breast, pancreas, ovary, gastric, prostate, hepatocellular, renal cell, and non-small cell lung carcinomas and lymphoma, in addition to multiple samples of fifteen other malignancies. For neoplasms of the colon, tissues representing the continuum of hyperplasia through invasive carcinoma were evaluated. The results show that TRAIL-R2 is expressed on a broad variety of human tumor types. Strong staining for TRAIL-R2 was most frequent in tumors of the colon, stomach and pancreas. In neoplasms of the colon, a trend was observed towards increased expression of TRAIL-R2 with disease progression, although some early lesions, including polyps, can have strong staining for TRAIL-R2. TRAIL-R2 is detected in normal tissues, but widespread staining was uncommon.

A poster presented on November 1, entitled “HGS-TR2J, a Human, Agonistic, TRAIL Receptor-2 Monoclonal Antibody, Induces Apoptosis In Vitro, In Vivo Tumor Regression and Growth Inhibition in Several Human Tumor Cell Lines and Enhances the Anti-Tumor Activity of Platinum and Taxane Agents in Lung and Ovarian Tumor Cell Lines” (Abstract #383) ², described the results of preclinical studies designed to assess the in vitro and in vivo efficacy of HGS-TR2J in tumor cell lines alone or in combination with platinum or taxane chemotherapeutic agents. Tumor cell lines were evaluated for TRAIL receptor expression by flow cytometry and sensitivity to HGS-TR2J and chemotherapeutic agents in vitro. The in vivo efficacy of HGS-TR2J, alone and in combination with chemotherapeutic agents, was evaluated in xenograft tumor models. The results described at ESMO demonstrate the following: HGS-TR2J increases in vitro toxicity of carboplatin or cisplatin in ovarian and non-small cell lung cancer (NSCLC) cell lines. HGS-TR2J elicits high-level apoptosis within twelve hours of treatment in xenograft tumors. HGS-TR2J induces tumor regression in xenograft models of renal cancer, esophageal cancer, and NSCLC. HGS-TR2J induces tumor regression or growth inhibition in combination with taxane and platinum agents in xenograft models of breast cancer (with paclitaxel), NSCLC (with docetaxel), and ovarian cancer (with cisplatin). HGS-TR2J increases survival in two orthotopic models of NSCLC alone or in combination with cisplatin. These data demonstrate the potency and activity of HGS-TR2J across a spectrum of tumor types in multiple settings and in combination with two important classes of chemotherapeutic agents.

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.

The HGS-ETR2 agonistic human monoclonal antibody was made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology. ⁴ Human Genome Sciences holds the commercial rights to the drug.

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. ^5-33 Human Genome Sciences took the approach of developing human monoclonal antibodies that would specifically bind either TRAIL Receptor 1 or TRAIL Receptor 2, to trigger apoptosis in cancer cells, in much the same way that native TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) triggers it, but with the advantage of a longer half-life and an exquisite specificity for either TRAIL Receptor 1 or TRAIL Receptor 2. The company has three agonistic antibodies to TRAIL Receptors 1 and 2 in clinical development for potential use in the treatment of cancer: HGS-ETR1 (TRAIL-R1 mAb), HGS-ETR2 (TRAIL-R2 mAb), and HGS-TR2J (TRAIL-R2 mAb).

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. Halpern W, et al. TRAIL-R2 protein expression in normal and tumor tissues. 29th Congress of the European Society for Medical Oncology (ESMO), 2004: Abstract #83.
2. Humphreys R, et al. HGS-TR2J, a Human, Agonistic, TRAIL Receptor-2 Monoclonal Antibody, Induces Apoptosis In Vitro, In Vivo Tumor Regression and Growth Inhibition in Several Human Tumor Cell Lines and Enhances the Anti-Tumor Activity of Platinum and Taxane Agents in Lung and Ovarian Tumor Cell Lines. 29th Congress of the European Society for Medical Oncology (ESMO), 2004: Abstract #383.
3. (HGSI Press Release). Human Genome Sciences Announces Joint Development of Antibody for the Treatment of Cancer with Kirin. December 3, 2002.
4. (HGSI Press Release) Human Genome Sciences And Cambridge Antibody Technology Commit To Exclusive Development Of Antibody To Trail Receptor-2. May 20, 2002.
5. Humphreys R, 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.
6. Halpern W, 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.
7. Krishnan B, Ormerod MG, Kaye SB, Jackman AL. 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.
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CONTACTS:
David C. Stump, M.D.
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240/314-4400
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301/251-6003