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| HUMAN GENOME SCIENCES REPORTS INTERIM RESULTS OF PHASE 1 CLINICAL TRIALS OF LYMPHORADTM 131 AT 45TH ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY | |
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- Early data show that LymphoRad131 is well tolerated and biologically active in patients with non-Hodgkin's lymphoma - - Emerging clinical and preclinical data continue to provide strong support for ongoing clinical development of LymphoRad, TRAIL-R1 mAb, and TRAIL-R2 mAb - ROCKVILLE, Maryland – December 9, 2003 – Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that interim results of an ongoing Phase 1 clinical trial of LymphoRadTM 131 demonstrate that the drug is well tolerated and biologically active in patients with non-Hodgkin's lymphoma. Safety, pharmacology, and biological activity data were presented this week at the 45th Annual Meeting of the American Society of Hematology, which concludes today in San Diego, CA. Company scientists also presented the results of preclinical studies of TRAIL-R1 and TRAIL-R2 agonistic human monoclonal antibodies. LymphoRad131 is a radioiodinated form of B-lymphocyte stimulator (BLyS), a novel human protein discovered by Human Genome Sciences.1 Phase 1 clinical trials of LymphoRad131 are ongoing to evaluate its safety and pharmacology in patients with multiple myeloma and in patients with non-Hodgkin's lymphoma.2 A poster presented on December 6 entitled "Early Clinical Data for LymphoRad-131 (LR131; Iodine I-131 Labeled B-Lymphocyte Stimulator) in Patients with Relapsed/Refractory Non-Hodgkin's Lymphoma" described preliminary safety, pharmacology, and biological activity data from an ongoing multi-center, open-label, dose-escalation Phase 1 clinical trial of LymphoRad131 in patients with relapsed, refractory non-Hodgkin's lymphoma [Abstract 1481].3 A poster presented on December 7 entitled "LymphoRad-131 Pharmacokinetics and Dosimetry in Ongoing Phase I Multiple Myeloma and Non-Hodgkin's Lymphoma Trials" described preliminary pharmacology results from the ongoing Phase 1 clinical trial in patients with non-Hodgkin's lymphoma, and from an ongoing multi-center, open-label, dose-escalation Phase 1 clinical trial in patients with relapsed, refractory multiple myeloma [Abstract 2537].4 The ongoing study in patients with non-Hodgkin's lymphoma is designed to evaluate six escalating doses of radioactivity (0.35 millicurie (mCi) per kilogram (kg), 0.70 mCi/kg, 1.35 mCi/kg, 2.0 mCi/kg, 2.5 mCi/kg, or 3.0 mCi/kg) and three escalating doses of BLyS protein (10 micrograms (mcg)/kg, 30 mcg/kg, 75 mcg/kg). Safety, dosimetry, and biological activity data were presented on six patients treated to date with sufficient follow up data. Pharmacokinetic data were presented on the three patients treated in the first dose cohort. The ongoing study in patients with relapsed, refractory multiple myeloma is designed to evaluate five escalating doses of radioactivity (10 mCi/m2, 15 mCi/m2, 20 mCi/m2, 25 mCi/m2, or 30 mCi/m2) and three escalating doses of BLyS protein (10 mcg/kg, 30 mcg/kg, 75 mcg/kg). Pharmacokinetic and dosimetry data were presented on the three patients treated in the first dose cohort. In both studies, patients receive an initial dosimetry (imaging) dose of 5 to 7 mCi of LymphoRad131 followed by daily anterior/posterior whole-body imaging for one week. One to two weeks following the imaging dose, the therapeutic dose of LymphoRad131 is administered. A minimum of one anterior/posterior whole-body image is taken one to two days following treatment. The primary purpose of both trials is to determine LymphoRad131's tolerability and safety. Biodistribution, pharmacokinetics, and biological activity also are being evaluated. Data were presented on six patients with relapsed, refractory follicular non-Hodgkin's lymphoma who have completed treatment and sufficient follow up to date in the Phase 1 study. Patients have been treated previously with single-agent and multi-agent chemotherapy, limited field external beam radiation therapy, or rituximab with or without concomitant chemotherapy. Patients have not previously received high-dose chemotherapy or hematopoietic stem cell transplantation. Interim results show that LymphoRad131 is well tolerated, has a favorable pharmacokinetic profile, and shows signs of anti-tumor activity in patients with relapsed, refractory non-Hodgkin's lymphoma. There were no drug-related, non-hematological adverse events reported. As expected based on LymphoRad131's mechanism of action, some hematological adverse events were observed. These events were minimal, manageable, and not dose-limiting. As expected based on preclinical research, nuclear imaging following the imaging and therapeutic doses confirm that LymphoRad131 targets tumor cells in all six of the patients with non-Hodgkin's lymphoma. CT and FDG-PET scans following the therapeutic doses show that LymphoRad131 exhibits signs of anti-tumor activity, with two of the six patients evaluated to date experiencing partial responses (tumor shrinkage) and two patients experiencing stable disease (no new tumor growth). The remaining two patients evaluated to date have experienced progressive disease. Preliminary pharmacokinetic data from the first dose cohorts of LymphoRad131 in each study show that the administered radioactivity has a terminal half-life of approximately eighteen to twenty-three hours, which is much shorter than is reported for radiolabeled anti-CD20 antibodies. Biodistribution and dosimetry data show that normal tissues (i.e., liver, lung, and kidney) were exposed to only low levels of radioactivity at all levels of radioactivity and BLyS protein administered to date. These levels are considered within the acceptable range for this type of therapy. Andrew Belch, M.D., Cross Cancer Institute, Edmonton, Alberta, said, "Radioimmunotherapy for the treatment of B-cell tumors is emerging as a promising area of exploration. Non-Hodgkin's lymphomas are known to be highly susceptible to the lethal effects of radiation. LymphoRad combines the B-cell binding specificity of BLyS with the well-known properties of the radioactive isotope iodine-131. We are encouraged by the preliminary data from the ongoing Phase 1 clinical trial in patients with non-Hodgkin's lymphoma that show that LymphoRad is well tolerated and shows signs of antitumor activity. We look forward to continuing to evaluate LymphoRad's potential as a treatment for non-Hodgkin's lymphoma in the ongoing Phase 1 study." Human Genome Sciences continues to evaluate the safety and pharmacology of LymphoRad131 in ongoing Phase 1 clinical trials in patients with non-Hodgkin's lymphoma and in patients with multiple myeloma. Investigators are currently escalating to higher doses to determine the maximum tolerated dose. Enrollment in both trials is expected to continue into 2004. Human Genome Sciences also presented results of preclinical studies of TRAIL-R1 mAb and TRAIL-R2 mAb on December 8 and 9. The company currently is conducting Phase 1 clinical trials of TRAIL-R1 mAb (HGS-ETR1) and of TRAIL-R2 mAb (HGS-ETR2) for the treatment of cancer.5, 6 The TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) Receptor-1 and TRAIL Receptor-2 proteins were originally identified by Human Genome Sciences. TRAIL-R1 mAb specifically recognizes the TRAIL Receptor-1 protein. TRAIL-R2 mAb specifically recognizes the TRAIL Receptor-2 protein. Both receptors are found on the surface of a number of solid tumor and hematopoietic cancer cells. TRAIL-R1 mAb and TRAIL-R2 mAb mimic the activity of native TRAIL. As such, they are considered agonistic antibodies. Binding of the antibodies to their respective receptor triggers cell death. A poster presented on December 8 entitled "Human Agonistic Anti-TRAIL Receptor Antibodies, HGS-ETR1 and HGS-ETR2, Induce Apoptosis in Diverse Hematological Tumor Lines" described results of preclinical studies designed to evaluate receptor expression and sensitivity to human agonistic monoclonal antibodies to TRAIL-R1 (HGS-ETR1) and TRAIL-R2 (HGS-ETR2) in cell lines derived from multiple myelomas, acute lymphoblastic leukemias (ALL), non-Hodgkin's lymphomas, and chronic myelogenous leukemias [Abstract 3316].7 Results show that both HGS-ETR1 and HGS-ETR2 are capable of inducing dose-dependent cell death across all malignancies tested, but with some variability among the cell lines. While most cell lines expressed mRNA for either TRAIL-R1 or TRAIL-R2 and low to moderate amounts of surface TRAIL-R1 and TRAIL-R2, neither was a reliable predictor of cell line sensitivity to the antibodies, which suggests that other signaling components, not the level of receptor expression, influences the sensitivity of a cell line to the antibodies. Induction of apoptosis in cells responding to either antibody was confirmed by caspase activation and annexin V binding. An oral presentation today entitled "Activity of Selective Agonistic Monoclonal Antibodies to TRAIL Death Receptors R1 and R2 in Primary and Cultured Tumor Cells of Hematological Origin" described results of preclinical studies designed to examine the efficacy of novel human agonistic monoclonal antibodies to TRAIL-R1 (HGS-ETR1) and TRAIL-R2 (HGS-ETR2) in cultured and primary tumors of hematological origin [Abstract 799].8 Results of previously reported experiments demonstrate that HGS-ETR1 and HGS-ETR2 bind specifically to their respective receptors, and rapidly induce apoptosis in experimental models of various human cancers. Data were presented today from studies evaluating the receptor expression and sensitivity of cell lines to each antibody in in vitro models of human Hodgkin's lymphoma, acute T-cell lymphocytic leukemia, and acute promyelocytic leukemia. Results show that treatment with HGS-ETR1 or HGS-ETR2 induces dose-dependent cell death in a wide variety of such cell lines. Cell surface expression of the TRAIL-R1 and TRAIL-R2 receptors did not correlate with cell line sensitivity to either antibody. Induction of apoptosis in cells responding to either antibody was confirmed by caspase activation and annexin V binding. Results of additional in vitro studies demonstrate that HGS-ETR1 and HGS-ETR2 show cell killing activity in tumor cells freshly isolated from patients with hematological malignancies (non-Hodgkin’s lymphomas, n = 13; chronic lymphocytic leukemia, n = 14; and chronic myelogenous leukemia, n = 4). HGS-ETR1 and HGS-ETR2 were each active in killing greater than ten percent of the cells in 71% (22/31) of the samples. David C. Stump, M.D., Senior Vice President, Drug Development, said, "The interim results presented from the ongoing Phase 1 clinical trials of LymphoRad are encouraging. Data show that LymphoRad is well tolerated, with no drug-related non-hematological adverse events, and only minimal hematological toxicity, reported to date. More importantly, the drug is behaving as predicted. Interim results show that LymphoRad delivers potentially therapeutic doses of radioactivity with specificity to tumors, while exposing normal tissues to low, allowable levels of radioactivity due to its short half-life. In addition, even at the low doses tested to date, we have observed signs of anti-tumor activity, with four of the six patients treated to date experiencing stable disease or partial responses. It is important to note that these results are preliminary and involve only a small number of patients. We look forward to continuing to evaluate LymphoRad's potential to treat B-cell cancers such as non-Hodgkin's lymphoma and multiple myeloma in the ongoing Phase 1 clinical trials. We also are encouraged by the preclinical evidence that continues to emerge in support of the therapeutic potential of our agonistic human monoclonal antibodies to the TRAIL-R1 and TRAIL-R2 receptors." Craig A. Rosen, Ph.D., President, Research and Development, said, "The distribution of LymphoRad receptors differs from that of CD-20, the target of three other drugs, Bexxar, Rituxan, and Zevalin, that also may be used to treat some B-cell tumors. The LymphoRad receptors are present on multiple myelomas, whereas the receptors for Bexxar, Rituxan, and Zevalin are generally not. Additionally, pre-B cells needed to replenish the normal B-cell population lack the LymphoRad receptor, but carry CD-20, suggesting that pre-B cells may escape killing by LymphoRad, thus potentially mitigating drug-related side effects." William A. Haseltine, Ph.D., Chairman and Chief Executive Officer, said, "Cancer is a major focus of our research and development activities, along with immunology and infectious disease, and we look forward to continuing the development of LymphoRad for the treatment of B-cell cancers,2 and TRAIL-R1 and TRAIL-R2 agonistic human monoclonal antibodies for the treatment of various malignancies.5, 6" For additional information on Human Genome Sciences, please visit our web site at www.hgsi.com. For more information on LymphoRad131, see www.hgsi.com/products/LR131.html. For more information on TRAIL-R1 mAb, see www.hgsi.com/products/TRAIL-R1_mAb.html. For more information on TRAIL-R2 mAb, see www.hgsi.com/products/TRAIL-R2_mAb.html. Health professionals interested in the LymphoRad, TRAIL-R1 mAb, or TRAIL-R2 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, www.hgsi.com/products/request.html, or by calling us 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. 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:
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