New England Journal of Medicine Study Supports Role of Nexell Technology in Engineering Novel Stem Cell Therapies.

Business Editors & Health/Medical Writers

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IRVINE, Calif.--(BW HealthWire)--March 21, 2001

Data From NIH Provide Basis for Nexell Clinical Development Program in

Inherited Blood Disorders

Results of a study published in the March 22 issue of the New England Journal of Medicine offer evidence that an experimental form of stem cell transplantation, facilitated by stem cell selection, provides a new therapeutic option for treating a rare and potentially fatal inherited blood disorder called chronic granulomatous disease (CGD)(a), Nexell Therapeutics Inc. (Nasdaq: NEXL) announced.

In the study, researchers at the National Institutes of Health (NIH) led by Mitchell Horwitz, M.D., and Harry L. Malech, M.D., utilized a non-myeloablative (not destructive of bone marrow) conditioning regimen to prepare patients to receive selected donor stem cells. Selection was performed with an investigational version of the Isolex(R) 300i Magnetic Cell Selection System to further deplete T-cells from the stem cell grafts in an effort to prevent severe graft-versus-host disease (GVHD), a potentially fatal complication associated with transplantation of donor stem cells.

"Dr. Horwitz and his colleagues have pioneered a safer way to give CGD patients a new, properly functioning immune system from a matched related donor. Long term acceptance of these stem cell grafts is believed to represent a cure for this disease," said Dennis Van Epps, Ph.D., Vice President, Research and Development at Nexell Therapeutics. "Their results confirm that by delivering a standard dose of stem cells without variable quantities of T-cells, the risks of the procedure may be reduced."

On the basis of these independent results, Nexell will seek U.S. Food and Drug Administration (FDA) approval to begin its own registration trial in support of an application to treat CGD, and later, other inherited blood and immune disorders, with engineered stem cell grafts.

"We are currently in discussions with the FDA and hope to file an IND within the next few months," said Dr. Van Epps. "The expertise and resources at NIH offer an exciting opportunity to study this promising treatment further. CGD is also a logical target because success with this rare disease may help extend the stem cell transplant approach to a broad group of non-malignant, inherited blood and immune disorders, such as thalassemia, Wiskott-Aldrich syndrome, Gaucher's disease, even sickle cell anemia."

CGD afflicts more than 1,000 Americans and approximately 25,000 people worldwide. It is caused by a group of gene mutations that prevent white blood cells called neutrophils from producing oxygen compounds, their main weapon against bacteria or fungi. As a result, patients suffer from recurrent, often life-threatening infections and the formation of inflammatory nodules called granulomas in their lungs, livers and other organs. To help prevent potentially fatal complications, most CGD patients must receive antibiotics and other drugs on a regular basis. Despite the availability of this treatment, the annual mortality rate for CGD is two to five percent.

In their paper, the investigators report results for ten CGD patients (5 adults and 5 children) who underwent allogeneic (donor) stem cell transplantation from HLA-identical siblings. Following low intensity, non-myeloablative marrow conditioning, each patient received a CD34+ selected, T-cell depleted allograft, followed later by donor lymphocyte infusions (30 days or more following transplant) to support donor stem cell engraftment.

Success in the study was gauged by the persistence of donor cells over time and improvement in the signs and symptoms of the disease. All patients had prompt hematopoietic reconstitution, requiring minimal transfusion support. Full or partial donor stem cell engraftment was accomplished in 8 of 10 patients. Although two patients rejected their grafts, they had autologous hematopoietic recovery and essentially reverted to their original state. Only one of the five children in the study experienced a mild case of GVHD. Three adults enrolled in the study died. One death was related to GVHD, one to infection and the third to complications of a second transplant after the first was rejected. Because the researchers observed only one serious infection in 12 cumulative patient-years of follow-up in patients successfully transplanted, they concluded that they had achieved marked improvement in immune function. This was particularly significant because patients entering the study tended to have a severe form of the disease.

The authors note that their non-myeloablative method has a favorable safety profile compared to previously reported transplant procedures for non-malignant immunodeficiency disorders that utilize more toxic forms of marrow conditioning. By reviewing rates of serious infection following treatment with interferon gamma with their own results, the investigators also suggest that their regimen may be more effective than standard therapy. However, they caution that non-myeloablative stem cell transplantation should not be considered for patients who lack an HLA-matched donor and, since full immune reconstitution may take up to one year, the procedure still carries significant risk.

The Isolex(R) 300i Magnetic Cell Selection System is approved by the U.S. FDA as a restricted device for the selection of hematopoietic stem cells and the removal of tumor cells from autologous peripheral blood grafts used to restore cancer patients' immune and blood-forming systems following high-dose chemotherapy. Complete prescribing information is available in the Isolex(R) 300i package insert. Nexell is currently conducting a Phase III clinical registration trial with the Isolex(R) 300i System for the selection of stem cells and the removal of T-cells from allogeneic peripheral blood grafts from matched-related donors for use in this setting.

The Isolex(R) 300i System capable of sequential positive and negative selection used in this study is commercially available in Europe. This system may be used in the United States under Investigational Device Exemption (IDE) only. Such IDEs have been granted for investigational protocols with the Isolex(R) in gene therapy and dendritic cell therapy, engineered transplants with alternative donors, and for autoimmune diseases.

Nexell Therapeutics Inc.

Located in Irvine, California, Nexell Therapeutics Inc. (Nasdaq:NEXL) is a biotechnology company that is a leader in the clinical use of hematopoietic (blood-forming) stem cells. Nexell markets advanced technologies to facilitate ex vivo manipulation of cells for clinical and investigational treatment approaches in cancer, autoimmune, and genetic diseases, and is developing proprietary cell-based therapies that address major unmet medical needs. The Company's stem cell selection, cell culture and expansion, cell storage, and in vitro tumor diagnostic products are currently available in major world markets, including the U.S. and Europe. In addition to supporting internal clinical development, this commercial platform allows Nexell to participate broadly in outside research protocols that are helping to define the frontiers of cell-based medicine.

(a) ME Horwitz et al. Treatment of chronic granulomatous disease with non-myeloablative conditioning and a T-cell-depleted hematopoietic allograft. The New England Journal of Medicine 344:926-27 (2001).

More information about this study is available from the Web site of the National Institute of Allergy and Infectious Disease (NIAID), a component of the NIH, at www.niaid.nih.gov.

The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for certain forward-looking statements. The forward-looking statements contained in this release are subject to certain risks and uncertainties. Actual results could differ materially from current expectations. Among the factors which could affect the Company's actual results and could cause results to differ from those contained in the forward-looking statements contained herein are: the timely commencement and success of the Company's clinical trials and other research endeavors, delays in receiving FDA or other regulatory approvals, the development of competing therapies and/or technologies, the terms of any future strategic alliances, the possible need for additional capital, and any additional factors described from time to time in the Company's filings with the SEC.

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