Human Genome Sciences Reports Results of Preclinical Studies of Albuleukin(TM) and Trail-R1 and Trail-R2 Agonistic Human Monoclonal Antibodies at the Society for Biological Therapy - Preclinical Data Provide Strong Support for Ongoing Phase 1 Clinica
ROCKVILLE, Md., Nov 11, 2002 /PRNewswire-FirstCall via COMTEX/ -- Human Genome
Sciences, Inc. (Nasdaq: HGSI) described today data presented at the 17th annual
meeting of the Society for Biological Therapy held in San Diego from November
7-10, 2002. Company scientists presented the results of preclinical studies of
Albuleukin(TM), and TRAIL-R1 and TRAIL-R2 agonistic human monoclonal antibodies.
Albuleukin
Albuleukin is Human Genome Sciences' novel, long-acting form of interleukin-2. A
Phase 1 clinical trial of Albuleukin is currently under way to evaluate its
safety and pharmacology in patients with solid tumors.(1)
A poster presented on November 8, entitled Induction of Anti-B16 Melanoma
Responses in Mice by Albuleukin(TM), An Interleukin-2 (IL-2)/Human Serum Albumin
Fusion Protein (Poster #28), describes the results of a preclinical study
designed to assess Albuleukin's ability, compared with recombinant
interleukin-2, to control disease progression and improve survival outcomes at
the maximum tolerated dose in a mouse model of malignant melanoma that has
metastasized to the liver. The maximum tolerated dose for recombinant
interleukin-2 was determined to be 1.0 mg/kg/day administered in two doses per
day, whereas the maximum tolerated dose for Albuleukin was determined to be 1.75
mg/kg administered in one dose every other day. Results show that, at the
maximum tolerated dose, both Albuleukin and recombinant interleukin-2
significantly reduced the mean tumor size in mice. In addition, mice treated
with Albuleukin had a significantly decreased frequency of residual hepatic
tumor cells compared with mice treated with recombinant interleukin-2.
Furthermore, Albuleukin significantly improved the survival of mice relative to
interleukin-2.
Summary
These results show that Albuleukin has an improved ability to mediate a potent
anti-tumor response, with less frequent dosing and less administered drug on a
molar basis, compared with recombinant interleukin-2, in a mouse model of human
malignant melanoma that has metastasized to the liver. The data also
demonstrated improved survival outcomes for Albuleukin compared with recombinant
interleukin-2. In addition, results suggest that sustained drug plasma levels
may be key to optimizing the anti-tumor response.
TRAIL-R1 And TRAIL-R2 Agonistic Human Monoclonal Antibodies
Human Genome Sciences is currently enrolling patients in a Phase 1 clinical
trial to evaluate the safety and pharmacology of TRAIL-R1 mAb in patients with
advanced tumors.(2,3,4) TRAIL-R2 mAb is in advanced preclinical development.(5)
Human Genome Sciences hopes to file an Investigational New Drug (IND)
application in the first half of 2003, seeking clearance from the U.S. Food and
Drug Administration to begin clinical development of TRAIL-R2 mAb for use in the
treatment of cancer. The TRAIL (tumor necrosis factor apoptosis-inducing ligand)
Receptor-1 and TRAIL Receptor-2 proteins were discovered by Human Genome
Sciences. TRAIL Receptor-1 human monoclonal antibody (TRAIL-R1 mAb) specifically
recognizes the TRAIL Receptor-1 protein, found on the surface of a number of
solid tumor and hematopoietic cancer cells. TRAIL Receptor-2 human monoclonal
antibody (TRAIL-R2 mAb) specifically recognizes the TRAIL Receptor-2 protein,
similarly found on the surface of a number of solid tumor and hematopoietic
cancer cells. Both TRAIL-R1 mAb and TRAIL-R2 mAb mimic the activity of native
TRAIL. As such, they are considered agonistic antibodies. Binding of TRAIL-R1
mAb to TRAIL Receptor-1, or of TRAIL-R2 mAb to TRAIL Receptor-2, triggers cell
death.
An oral presentation on November 10, entitled TRAIL-R1 and TRAIL-R2 Human
Agonistic Monoclonal Antibodies Display In Vitro and In Vivo Activity on Human
Tumor Cells, described data from preclinical studies of TRAIL-R1 mAb and
TRAIL-R2 mAb. The objective of the studies was the generation and
characterization of human agonistic monoclonal antibodies to TRAIL-R1 and
TRAIL-R2 that might be useful therapeutics for human cancer. Such monoclonal
antibodies were developed and analyzed for their in vitro ability to bind to
TRAIL-R1 or TRAIL-R2, respectively, and promote apoptosis.
* Results of these preclinical studies show that TRAIL-R1 mAb binds with
high affinity and specificity to the human TRAIL Receptor-1 protein. In
vitro data demonstrate that TRAIL-R1 mAb induces apoptosis in colon,
uterine, and lymphoma cancer cell lines expressing the TRAIL Receptor-1
protein. Furthermore, TRAIL-R1 mAb inhibited tumor growth in a mouse
model of human colon carcinoma and reduced the growth of pre-established
uterine tumors in athymic mice by up to fifty percent. In vivo data
also show that the anti-tumor activity of TRAIL-R1 mAb is enhanced when
given in combination with the chemotherapeutic agent, topotecan.
* Results of preclinical studies evaluating TRAIL-R2 mAb show that TRAIL-
R2 mAb binds with high affinity and specificity to the human TRAIL
Receptor-2 protein. In vitro data demonstrate that TRAIL-R2 mAb induces
apoptosis in colon and breast cancer cell lines expressing the TRAIL
Receptor-2 protein. TRAIL-R2 mAb was shown to inhibit tumor growth or
induce tumor regression in mouse models of human colon and breast
cancer. A single injection of TRAIL-R2 mAb reproducibly reduced tumor
size by eighty percent in one mouse model of human colon cancer, and was
active in inducing tumor regression in a mouse model of large human
colon tumors. A TUNEL analysis of TRAIL-R2 mAb treated tumors
demonstrated that reduction in tumor size was mediated through
apoptosis. (TUNEL analyses use immunohistochemistry to identify DNA
fragmentation in nuclei of cells undergoing apoptosis.)
Summary
The results of these preclinical studies reinforce other preclinical data
suggesting that TRAIL-R1 mAb and TRAIL-R2 mAb are attractive candidates for the
treatment of cancer.
For additional information on Human Genome Sciences, please visit the web site
at hgsi.com . For more information on Albuleukin, see
hgsi.com . For more information on TRAIL- R1
mAb, see hgsi.com .
Health professionals interested in the Albuleukin or TRAIL-R1 mAb trials or any
other study involving HGSI products are encouraged to inquire via the Contact Us
section of the Human Genome Sciences web site,
hgsi.com , or by calling Human Genome Sciences
at (301) 610-5790, extension 3550.
Human Genome Sciences is a company with the mission to treat and cure disease by
bringing new gene-based drugs to patients.
HGS, Human Genome Sciences, and Albuleukin 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) (HGSI Press Release) Human Genome Sciences Initiates Trial Of
Albuleukin(TM), A Recombinant Human Protein For Treating Solid Tumor
Cancers. January 7, 2002.
(2) (HGSI Press Release) Cambridge Antibody Technology And Human Genome
Sciences Announce Second Drug Partnership. January 8, 2002
(3) (HGSI Press Release) Human Genome Sciences Initiates Clinical
Development Of A Novel Anticancer Drug. April 30, 2002.
(4) (HGSI Press Release) Takeda Exercises Option To Develop Novel Human
Genome Sciences Antibody Drug In Japan. August 14, 2002.
(5) (HGSI Press Release) Human Genome Sciences And Cambridge Antibody
Technology Commit To Exclusive Development Of Antibody To Trail
Receptor-2. May 20, 2002.
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SOURCE Human Genome Sciences, Inc.
CONTACT: David C. Stump, M.D., Senior Vice President, Drug Development,
+1-301-309-8504, Jerry Parrott, Vice President, Corporate Communications,
+1-301-315-2777, or Kate de Santis, Director, Investor Relations,
+1-301-251-6003
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