HUMAN GENOME SCIENCES REPORTS RESULTS OF ONGOING PHASE 1 CLINICAL TRIALS OF HGS-ETR1 IN PATIENTS WITH ADVANCED CANCERS

- Results of Phase 1 clinical studies support further evaluation of HGS-ETR1 in Phase 2 clinical trials both as a single agent and in combination with chemotherapy -

- Data presented at 16 th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics -

ROCKVILLE, Maryland – September 29, 2004 – Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that the results of ongoing Phase 1 clinical trials demonstrate the safety and tolerability of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL Receptor 1) 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.

Safety, pharmacokinetic and biological activity data from two Phase 1 studies of HGS-ETR1 were presented today at the 16^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland. The conference is jointly organized by the European Organisation for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI) and American Association for Cancer Research (AACR).

In an oral presentation at the EORTC-NCI-AACR Symposium’s plenary session, entitled “A Phase 1 Clinical Trial of HGS-ETR1, an Agonistic Monoclonal Antibody to TRAIL-R1, in Patients with Advanced Solid Tumors,” data were presented on thirty-nine patients treated to date in an ongoing open-label, dose-escalation clinical trial.¹ The median number of chemotherapeutic treatment regimens previously received was two, and ranged as high as nine. The patients were enrolled into seven cohorts (0.01, 0.03, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg) and received HGS-ETR1 administered intravenously on a 28-day or 14-day schedule. The primary purpose of the study is to determine the safety, maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetics of HGS-ETR1 in patients with relapsed or refractory advanced tumors. Disease response also is being evaluated. Available tumor tissue samples from patients participating in the trial will be evaluated for expression of the TRAIL Receptor-1 protein using immunohistochemical (IHC) techniques.

Results to date of the ongoing Phase 1 clinical trial 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 doses up to and including 10 mg/kg. The MTD has not been reached, and accrual in the trial continues at a dose of 10 mg/kg every 14 days. Dose-proportional pharmacokinetics were observed up to a dose of 1.0 mg/kg, with a terminal elimination half-life of 15 days. In seven patients treated at the 10 mg/kg dose level, the terminal elimination half-life of HGS-ETR1 was longer, averaging about 18 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.

A poster entitled “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” (Abstract #208) presented data on twenty-four patients treated to date in an open-label, dose-escalation clinical trial currently ongoing at two centers in Canada.² All patients admitted to the trial have relapsed or refractory disease and had received prior anti-cancer treatments (chemotherapy, radiotherapy, or hormone therapy). To date, twenty-four patients have been enrolled into five cohorts (0.01, 0.03, 0.3, 3.0, or 10.0 mg/kg) and received HGS-ETR1 administered intravenously every 28 days. Patients continue to be enrolled into the 10 mg/kg dose cohort. The study design calls for enrollment of an additional cohort at a dose of 20 mg/kg. Patients are treated every 28 days in the absence of disease progression or dose-limiting toxicities. The primary objective of the trial is to evaluate the safety and tolerability of repeated doses of HGS-ETR1 administered intravenously in patients with advanced solid tumors or non-Hodgkin’s lymphoma. The secondary objectives are to evaluate the pharmacokinetics of repeated doses of HGS-ETR1 and to assess tumor response.

Results to date of 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. The median number of treatment cycles delivered is two (1-12). Stable disease has been observed in eight patients for greater than two cycles. Preliminary data indicate that the pharmacokinetics of HGS-ETR1 are dose-proportional up to 0.3 mg/kg. The trial continues to enroll patients.

An additional poster presented at the EORTC-NCI-AACR Symposium, “Variable Distribution of TRAIL Receptor 1 in Primary Human Tumor and Normal Tissues” (Abstract #225), described the results of a preclinical study designed to identify specific malignancies that are most likely to express TRAIL Receptor 1.³ 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 ⁴ and Fox Chase Cancer Center, used a highly specific immunohistochemical assay to evaluate 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.

Roger B. Cohen, M.D., Director, Phase 1 Clinical Trials Program, Fox Chase Cancer Center, Philadelphia, said, “The Phase 1 clinical results we presented today demonstrate that HGS-ETR1 is well tolerated and can be safely and repetitively administered to patients with advanced malignancies. We have seen no evidence of drug-related hematological or hepatic toxicity at the dose levels administered to date. We have not reached a maximum tolerated dose, and we have seen preliminary evidence of biological activity. Patient accrual continues in the ongoing Phase 1 trials. Further evaluation of HGS-ETR1 is appropriate in Phase 2 clinical trials, both as a single agent and in combination with chemotherapy.”

David C. Stump, M.D., Executive Vice President, Drug Development, said, “We continue to be encouraged by the results emerging from our ongoing Phase 1 clinical trials of HGS-ETR1. The data show that HGS-ETR1 is well tolerated in patients with advanced solid tumors or non-Hodgkin’s lymphoma. Stable disease has been observed in a number of patients in these studies as well. Based on the encouraging interim clinical results from our Phase 1 studies, along with the strongly supportive preclinical evidence^{1-3, 6-11}, we announced at the beginning of September that we have advanced HGS-ETR1 to a Phase 2 clinical trial in patients with relapsed or refractory non-small cell lung cancer.⁵ We plan to initiate additional Phase 2 clinical trials of HGS-ETR1 in the weeks and months to come.”

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.¹² 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 (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.

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Footnotes:

1. 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.
2. 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.
3. 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.
4. (HGSI Press Release) Human Genome Sciences Announces License Agreement with DakoCytomation for Development of Pharmacogenomic Diagnostic Assays. March 31, 2004.
5. (HGSI Press Release) Human Genome Sciences Advances Anti-Cancer Drug to Phase 2 Clinical Development. September 8, 2004.
6. A.W. Tolcher, 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.
7. L.H. Le, et al. 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. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #2533.
8. 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.
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. Ashkenazi A. et al. Safety and anti-tumor activity of recombinant soluble APO2 ligand. J Clin Inv July 1999; 104(2): 155-162.
12. (HGSI Press Release) Cambridge Antibody Technology and Human Genome Sciences Announce Second Drug Partnership. January 8, 2002.

FOR IMMEDIATE RELEASE
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

ARIAD REPORTS TUMOR REGRESSION WITH AP23573 AS A SINGLE AGENT
IN PATIENTS WITH RELAPSED AND/OR REFRACTORY CANCER

Updated Phase 1 Clinical Results on Novel mTOR Inhibitor Presented at
International Cancer Symposium

Cambridge, MA, September 30, 2004 – ARIAD Pharmaceuticals, Inc. (Nasdaq:
ARIA) today
announced, for the first time, updated results of two Phase 1 clinical
trials of its novel mTOR
inhibitor, AP23573 as a single agent, showing documented tumor
regression in patients with
advanced cancers – most of whom had progressive disease upon entering
the trial and
virtually all of whom had failed alternative treatments. These clinical
results are being
presented today at the 2004 EORTC-NCI-AACR Symposium on Molecular
Targets and
Cancer Therapeutics in Geneva, Switzerland.
Combined Trial Results: Anti-tumor Responses
Of 49 evaluable patients in the two trials, tumor regression was
demonstrated in 9 patients (4
“partial responses” by RECIST with at least 30% reduction in tumor size
and 5 “minor
responses” with 15% to 29% reduction). In an additional 15 patients,
disease stabilization
was achieved. Overall, 49% (24 of 49) of the patients in the two trials
had documented antitumor
responses (including partial and minor responses and stable disease),
with a median
response of 5 months in those demonstrating anti-tumor responses,
extending to greater than
18 months – the longest treatment to date.
Anti-tumor responses were demonstrated in 9 different refractory and/or
relapsed cancers,
including all evaluable patients with sarcoma (5 of 5), kidney cancer (7
of 7) and lymphoma (1
of 1), as well as 2 of 3 patients with non-small cell lung (NSCL) cancer.
“We are extremely encouraged by the number of patients with relapsed
and/or refractory
cancer who demonstrated tumor regression with AP23573 in Phase 1
clinical trials, as well as
the breadth of tumors that are responding to our novel mTOR inhibitor,”
said Harvey J. Berger,
M.D., chairman and chief executive officer of ARIAD. “As a clinician, I
was particularly
struck by the results in one patient with a Ewing’s sarcoma who had
received nine prior
anticancer regimens. After four cycles of AP23573, CT scans showed a 62%
reduction in the
size of the mass; this patient continues on study. Phase 2 studies of
AP23573 are ongoing in
patients with hematologic cancers and solid tumors.”
Daily Dosing Trial Results
In the 27 evaluable patients in the daily dosing trial – the dosing
regimen being used in
current Phase 2 clinical trials – AP23573 produced tumor regression in 7
patients:

• Partial response – Sarcoma, lymphoma, and NSCL cancer (1 each)
• Minor response – Sarcoma, NSCL, kidney, and thyroid cancers (1 each).
An additional 9 patients in this trial had stabilization of their
disease (overall 59% with
anti-tumor response).
Weekly Dosing Trial Results
In the 22 evaluable patients in the weekly dosing trial, AP23573 also
produced tumor
regression in 2 patients, both with particularly difficult-to-treat
cancers, even when the drug
was administered only once each week:
• Partial response – Bladder cancer (1) (unconfirmed, repeat scans pending)
• Minor response – Mesothelioma, a form of chest-cavity cancer (1).
An additional 6 patients in this trial had stabilization of their
disease (overall 36% with antitumor
response).
Additional Combined Trial Results
The daily dosing trial is ongoing at the Institute for Drug Development,
Cancer Therapy and
Research Center, San Antonio (M. Mita, M.D. and A. Tolcher, M.D.), and
the weekly dosing
trial is ongoing at the University of Chicago Cancer Center (A. Desai,
M.D. and M. Ratain,
M.D.).
AP23573 has been well tolerated by patients in both trials, with
generally mild or moderate,
readily reversible adverse events. The dose-limiting toxicity was severe
oral mucositis, an
inflammatory irritation of the mucous membranes of the mouth and a
common finding in
cancer patients on various types of treatments.
Pharmacodynamic assays on patient samples demonstrated a good
correlation of blood levels
of AP23573 with inhibition of AP23573’s molecular target, the protein
mTOR. Greater than
90% inhibition was observed within 1 hour after dosing in all patients
in both trials. With
daily dosing of AP23573, there was sustained inhibition of mTOR activity
for up to 10 days in
the majority of patients studied.
The pharmacokinetic (blood-clearance) profile of AP23573 was found to be
highly predictable
and reproducible, with a median half-life of 49 hours for all patients
with complete data in the
two trials. In contrast to other mTOR inhibitors in clinical trials,
AP23573 was stable in vivo
and is not a pro-drug.
About AP23573
The small-molecule drug, AP23573, starves cancer cells and shrinks
tumors by inhibiting the
critical cell-signaling protein, mTOR, which regulates the response of
tumor cells to nutrients
and growth factors, and controls tumor blood supply and angiogenesis
through effects on
Vascular Endothelial Growth Factor (VEGF).
About the Company
ARIAD is engaged in the discovery and development of breakthrough
medicines to treat cancer
by regulating cell signaling with small molecules. The Company is
developing a comprehensive
approach to patients with cancer that addresses the greatest medical
need – aggressive and
advanced-stage cancers for which current treatments are inadequate.
ARIAD also has an
exclusive license to pioneering technology and patents related to
certain NF-κB treatment
methods, and the discovery and development of drugs to regulate NF-κB
cell-signaling activity,
which may be useful in treating certain diseases. Additional information
about ARIAD can be
found on the web at http://www.ariad.com.
Some of the matters discussed herein are “forward-looking statements”
within the meaning of the
Private Securities Litigation Reform Act of 1995. Such statements are
identified by the use of words
such as “anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,”
“believe,” and other words and
terms of similar meaning in connection with any discussion of future
operating or financial
performance. Such statements are based on management’s current
expectations and are subject to certain
factors, risks and uncertainties that may cause actual results, outcome
of events, timing and
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These risks include, but are not limited to, risks and uncertainties
regarding the Company’s ability to
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law.
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CONTACT: Tom Pearson
(610) 407-9260
Kelly Lindenboom
(617) 621-2345