This excerpt taken from the HGSI 10-K filed Mar 15, 2005.
Genomics-Derived Human Monoclonal Antibody Drugs
LymphoStat-B is a fully human monoclonal antibody designed to inhibit the biological activity of B-lymphocyte stimulator, or BLyS. Preclinical studies indicate that higher than normal levels of BLyS may trigger autoimmune diseases by stimulating production of autoantibodies antibodies that attack and destroy the bodys own healthy tissues. Over-production of autoantibodies may be counteracted by reducing BLyS levels with LymphoStat-B. We are developing LymphoStat-B as a potential treatment for autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). LymphoStat-B has received a Fast Track Product designation from the FDA for the treatment of systemic lupus erythematosus, and has been selected for inclusion in the FDAs Continuous Marketing Application Pilot 2 Program. The Pilot 2 program provides for frequent scientific feedback and interactions based on a prospectively defined agreement between the FDA and participating companies.
In July 2004, we completed the enrollment, randomization and initiation of dosing for separate Phase 2 clinical trials of LymphoStat-B in RA and SLE. Each trial is designed to evaluate safety, tolerability and efficacy. A total of 283 patients with active moderate-to-severe rheumatoid arthritis who have failed prior treatment have been enrolled in the RA trial. A total of 449 patients with active systemic lupus erythematosus have been enrolled in the SLE trial. It is anticipated that the results of both of the Phase 2 studies of LymphoStat-B will be available in 2005, with the RA results expected in the Spring and the SLE results expected in the Fall. Based on the Phase 2 results, we plan to reach go/no go decisions regarding Phase 3 development of the compound in both indications. Assuming that the data emerging from the Phase 2 study in RA are sufficiently positive, we could initiate a Phase 3 clinical trial of LymphoStat-B in patients with rheumatoid arthritis in the second half of 2005.
HGS-ETR1 is a novel anticancer drug that specifically recognizes, binds to and activates the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptor-1 protein. This protein was discovered by
Human Genome Sciences and is found on the surface of a number of solid tumor and hematopoietic cancer cells.
In June and September 2004, we reported the interim results of two ongoing Phase 1 clinical trials of HGS-ETR1. The interim results demonstrate the safety and tolerability of HGS-ETR1 in patients with advanced solid tumors or non-Hodgkins lymphoma, and support further evaluation of HGS-ETR1 in Phase 2 clinical trials, both as a single agent and in combination with chemotherapy. Preliminary evidence of biological activity was reported.
In November 2004, we completed the enrollment and initial dosing of patients in an ongoing Phase 2 clinical trial of HGS-ETR1 to evaluate its efficacy, safety and tolerability in patients with advanced non-small cell lung cancer. In February 2005 and March 2005, respectively, we announced the completion of enrollment and initial dosing of patients in separate Phase 2 clinical trials of HGS-ETR1 for the treatment of colorectal cancer and non-Hodgkins lymphoma. Each of the trials is designed to evaluate the efficacy, safety and tolerability of HGS-ETR1 in patients with refractory or relapsed malignancies. In 2005, we plan to complete all three of the ongoing Phase 2 clinical trials of HGS-ETR1. In the second half of 2004, we also initiated two Phase 1b clinical trials to evaluate the safety and tolerability of HGS-ETR1 in combination with chemotherapeutic agents (with gemcitabine and cisplatin and with paclitaxel and carboplatin). Both studies are in patients with advanced solid malignancies. Based on the Phase 2 and Phase 1b data, we plan to reach go/no go decisions regarding single-agent and chemotherapy combination development of HGS-ETR1 as a treatment for cancer.
HGS-ETR2 and HGS-TR2J are novel anticancer drugs that specifically recognize and bind to the TRAIL receptor-2 protein. The TRAIL receptor-2 protein was originally identified by Human Genome Sciences, and is found on the surface of a number of solid tumor and hematopoietic cancer cells.
In September 2004, we reported the interim results of an ongoing Phase 1 clinical trial of HGS-ETR2. The interim results demonstrate that HGS-ETR2 can be administered safely and repetitively to patients with advanced solid tumors, and support continued dose-escalation of HGS-ETR2 in these patients. Stable disease was observed in some patients. In 2005, we plan to initiate Phase 2 clinical trials of HGS-ETR2 as a single agent, and to initiate Phase 1b clinical trials of HGS-ETR2 in combination with chemotherapeutic agents.
We began dosing patients for a Phase 1 clinical trial of HGS-TR2J in August 2004. The primary objectives of the study are to assess safety and tolerability. Pharmacokinetics and disease response also are being evaluated. Based on the results of the current Phase 1 clinical trial, we will make a decision regarding further clinical development of TR2J.
CCR5 mAb is entering Phase 1 clinical development as a treatment for HIV/ AIDS. We received clearance of this IND (Investigational New Drug) from the FDA in December 2004, and we now plan to proceed with a randomized, placebo-controlled, dose-escalation, multi-center Phase 1 clinical trial to evaluate the safety, tolerability and pharmacology of CCR5 mAb in patients who are infected with HIV-1.
The CCR5 receptor is a co-receptor on the cell surface that, together with CD4, mediates the binding of HIV-1 and its entry into the cell. Research has shown that the CCR5 receptor is the primary co-receptor for enabling HIV-1 transmission and replication from the early stages of disease through progression to AIDS. Preclinical studies demonstrate that CCR5 mAb binds specifically and with high affinity to human CCR5, prevents HIV-entry, demonstrates no agonistic activity or effector functions, and has a prolonged serum half-life.
ABthrax is a novel drug developed by Human Genome Sciences for the prevention and treatment of anthrax infections. ABthrax is a human monoclonal antibody that blocks the binding to cell surfaces of