ROCKVILLE, Maryland – October 13, 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 colorectal cancer.

The Phase 2 clinical trial is a multi-center, open-label study to evaluate the efficacy, safety and tolerability of HGS-ETR1 in patients with relapsed or refractory colorectal cancer. The Phase 2 clinical trial will be conducted in Germany, and will enroll a maximum of thirty patients. Each patient will receive 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. Disease response will be assessed using the RECIST Criteria (Response Evaluation Criteria in Solid Tumors), which were established in 2000 to provide an 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 colorectal cancer is one 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. In a separate press release today, Human Genome Sciences announced that it has begun dosing patients in a Phase 2 clinical trial of HGS-ETR1 in patients with non-Hodgkin’s lymphoma. ² On September 8, 2004, the company announced the initiation of a Phase 2 study of HGS-ETR1 in patients with non-small cell lung cancer. ³

Human Genome Sciences also announced today that it has initiated an open-label, dose-escalation Phase 1b clinical trial in The Netherlands to evaluate the safety and tolerability of HGS-ETR1 in combination with gemcitabine and cisplatin in patients with advanced solid malignancies.

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, “Colorectal cancer is the second-leading cause of cancer-related deaths in Western Europe and the United States. The overall five-year survival of patients with colorectal cancer is approximately fifty percent. Some twenty-five percent of patients present with metastatic disease, and approximately forty-fifty percent of patients eventually develop metastatic disease. Only about three percent of the patients who develop metastatic disease survive for five years.^4-7 Combinations of chemotherapeutic agents and, more recently, monoclonal antibodies, have demonstrated clinical benefit for patients with colorectal cancer, but the prognosis for these patients continues to be poor.^8-22 They often undergo multiple treatment regimens and still experience substantial morbidity and mortality. It is clear that a significant medical need exists for effective new therapeutic agents that may be used as single agents or in combination regimens. We look forward to evaluating HGS-ETR1 to determine the potential of this novel agonistic antibody for use in the treatment of patients with colorectal cancer.”

Florian Bieber, M.D., Vice President, Drug Development – Europe, said, “The European oncology community has shown a high level of interest in the ability of our TRAIL-receptor antibodies, including HGS-ETR1, 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. This interest has been heightened by the interim clinical results emerging from our Phase 1 trials. Human Genome Sciences Europe is pleased to play a growing role in working with our U.S. colleagues on the clinical development of HGS-ETR1 and other novel protein and antibody drugs to treat cancer and other diseases representing significant medical need.”

David C. Stump, M.D., Executive Vice President, Drug Development, said, “We are pleased to advance HGS-ETR1 to a Phase 2 clinical trial in patients with advanced colorectal cancer. The preclinical evidence in support of the evaluation of HGS-ETR1 in this indication is particularly strong.^23-29 The data that continue to emerge from our ongoing Phase 1 studies of HGS-ETR1 are encouraging as well.^30-35 Colorectal cancer is a devastating disease with high rates of mortality, and it is our hope that HGS-ETR1 will ultimately offer a new option for use in the treatment of patients who suffer from it. The Phase 2 study in colorectal cancer is one of a number of studies in a global clinical development program to evaluate the potential of HGS-ETR1 in the treatment of specific cancers. We also are initiating our second Phase 1b clinical study of HGS-ETR1 in combination with chemotherapy. The chemotherapeutic combination study will be conducted in The Netherlands. The study in colorectal cancer will be conducted in Germany. Both of these studies will take place under the direction of our clinical development team at Human Genome Sciences Europe³⁶ in collaboration with their colleagues in the United States. Our strengthening ability to conduct clinical trials on a worldwide basis will prove to be an important asset as we continue to advance our products through the clinical development and regulatory process.”

Craig A. Rosen, Ph.D., President and Chief Operating Officer, said, “The results of our preclinical studies demonstrate that TRAIL Receptor 1 is expressed on colon carcinoma primary tumor tissues and in several colon tumor cell lines. We recently presented the results of a preclinical study conducted in collaboration with scientists from DakoCytomation and Fox Chase Cancer Center that used a highly specific pharmacogenomic assay to identify specific malignancies most likely to express TRAIL Receptor 1. The results demonstrated that tumors of the colon, pancreas and lung had substantial staining for TRAIL Receptor 1, indicating that these tumors could be strong candidate indications for HGS-ETR1. Additionally, our own in vitro and in vivo preclinical studies show that HGS-ETR1 inhibits or reduces tumor growth in xenograft models of colorectal cancer, and can induce significant tumor regression in some models of the disease. Our studies also suggest that the activity of HGS-ETR1 may have therapeutic benefit in the treatment of cancer either as a single agent or in combination with chemotherapeutic agents. We look forward to the continuing clinical development of HGS-ETR1 for the treatment of colorectal, lung and other human malignancies.”^{23-29, 37-43}

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 16^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland.^30-32 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 thirty-nine patients treated to date in a Phase 1 study conducted in patients with advanced solid tumors.^{30, 32} 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 at a dose of 10 mg/kg every 14 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 twenty-four 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 MTD has not been reached. Stable disease has been observed in eight patients for greater than two cycles. The trial continues to enroll patients.^31-32

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.^{23-29, 37-45} 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.⁴⁶ 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:

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2. (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.
3. (HGSI Press Release) Human Genome Sciences Advances Anti-Cancer Drug to Phase 2 Clinical Development. September 8, 2004.
4. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5. Lyon, IARC Press, 2001;1.
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23. 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.
24. (HGSI Press Release) Human Genome Sciences Reports Results of Preclinical Studies of TRAIL-R1 and TRAIL-R2 Agonistic Human Monoclonal Antibodies at EORTC-NCI-AACR Symposium. October 1, 2004.
25. Pukac L, Kanakaraj P, Alderson R, 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.
26. Salcedo, Alderson R, 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.
27. Humphreys R, 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.
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29. Chuntharapai A, Dodge K, Grimmer K, et al. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J Immunol 2001; 166:4891-4898.
30. Cohen RB, 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.
31. Hotte SJ, 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.
32. (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.
33. Tolcher AW, et al. 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. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #3060.
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35. (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.
36. (HGSI Press Release) Human Genome Sciences Establishes New Subsidiary in Europe. January 23, 2003.
37. 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.
38. Georgakis GV, 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.
39. Gillotte D, Zhang Y, Poortman C, 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.
40. Humphreys R, Shepard L, Zhang Y, et al. Novel, agonistic, human anti-TRAIL receptor monoclonal antibodies, HGS-ETR1 and HGS-ETR2, are capable of potently inducing tumor regression and growth inhibition as single agents and in combination with chemotherapeutic agents in models of human NSCLC. Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston, November 2003.
41. Buchsbaum DJ, Zhou T, Grizzle WE, 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.
42. Nagane M, Pan G, Weddle JJ, 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.
43. Gliniak B, Le T. 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.
44. Ashkenazi A. Apo-2L/TRAIL in Cytokine Reference. Academic Press 2000.
45. Younes A, Kadin ME. Emerging applications for the tumor necrosis factor family of ligands and receptors in cancer therapy. J Clin Oncol 2003;21:3526-3534.
46. (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