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Published Data on IL13-PE38 Identifies Mechanism of Drug Action for The Treatment of Malignant Glioma


Posted on: 11/07/2002

Published Data on IL13-PE38 Identifies Mechanism of Drug Action for The Treatment of Malignant Glioma

Intratumoral Administration of IL13-PE38 Induces Apoptotic Cell Death in Human Malignant Glioma Tumor Xenografts

LAKE FOREST, Ill., Nov. 7 /PRNewswire-FirstCall/ -- NeoPharm, Inc. (Nasdaq: NEOL) announced today new findings for IL13-PE38 reported in the October issue of Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research ( http://mct.aacrjournals.org/ ). The research was conducted under the direction of Dr. Raj Puri and colleagues from the Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), as part of a collaboration between FDA and NeoPharm, Inc. under a Cooperative Research and Development Agreement (CRADA).

In a series of laboratory experiments designed to help define the molecular mechanisms for the therapeutic properties of the drug IL13-PE38, the authors identified that human glioma (brain) tumor cells that express the IL-13 receptor undergo programmed cell death, or apoptosis, following intratumoral administration of IL13-PE38, leading to regression of established tumors. IL13-PE38 appears to be tumor-selective and induces apoptosis, which persists after the drug is no longer detectable. These findings shed light on the molecular pathways of inducing apoptosis in malignant glioma tumors and subsequent tumor regression mediated by this receptor-targeted cytotoxin and will provide insights assessing IL13-PE38 tumor response and developing the optimal clinical regimen for treatment of malignant glioma.

"These data published by Dr. Puri and his group further support the potential of IL13-PE38 as a tumor selective agent for the treatment of malignant glioma, a dreadful and devastating disease," said James M. Hussey, President and CEO, NeoPharm, Inc. NeoPharm is currently conducting Phase I/II clinical trials for IL13-PE38 and has scheduled a meeting with the FDA in December to determine the requirements to begin Phase II/III clinical trials.

Background Information

The Mechanism of IL13-PE38 Compared with Standard Chemotherapy Malignant glioma cells, as compared to normal brain cells, express interleukin-13 (IL13) receptors at a high density. IL13 is an immune regulatory cytokine, or protein, secreted by cells. IL13-PE38 (a recombinant protein) is designed to detect and bind to IL13 receptors on the surface of malignant glioma cancer cells. It then selectively delivers a potent bacterial cytotoxic agent called PE38, derived from Pseudomonas bacterium to destroy tumor cells while sparing healthy surrounding cells. In contrast, conventional, non-specific chemotherapeutic drugs attack abnormal cancer cells by stopping them from dividing and reproducing, but can also damage normal cells because these agents are not selective for just cancer cells and are almost always administered systemically. This means that the systemic medicines are diffused throughout the body rather than being localized to one area, such as a tumor in the brain, and cannot discriminate between cancer and healthy cells. Common chemotherapy side effects occur when bone marrow is damaged and cannot produce enough red blood cells (causing weakness and fatigue), white blood cells (lowering the body's resistance to infections) or platelets (preventing blood from clotting properly, which can lead to excessive bleeding).

IL13-PE38, on the other hand, is being developed as a highly specific tumor-targeting agent. It is administered directly to the tumor through positive-pressure convection enhanced delivery (CED), which uses catheters inserted in the brain before and/or following surgical resection (removal) of the tumor. CED is designed to infuse IL13-PE38 directly to the tumor site and adjacent brain tissue to prevent recurrence of tumor cell growth. Investigators have sought to identify the optimum "therapeutic window" to provide patients with the safest, most effective dose levels at sufficient toxic concentrations to kill tumor cells while minimizing toxic exposure to healthy tissues.

Phase I/II IL13-PE38 Clinical Program

IL13-PE38 is currently under investigation in three ongoing Phase I/II clinical trials. The first IL13-PE38 clinical study is being conducted through the NCI Clinical Trial Evaluation Program (CTEP)-funded New Approaches to Brain Tumor Therapy (NABTT) Consortium. Johns Hopkins University Medical Center is the coordinating site for NABTT. The first human clinical data on IL13-PE38 from this study was presented last Fall at the Sixth Annual Meeting of the World Federation of Neuro-Oncology/Society for Neuro-Oncology (SNO). These data indicated that IL13-PE38 might have potential as a safe and effective treatment for malignant glioma. Noticeable response to IL13-PE38 was observed in two of six patients in the NABTT study at the initial dose level. One patient, who was treated with IL13-PE38, subsequently underwent surgical removal of the tumor mass. A histopathologic evaluation following surgery found IL13-PE38 effective in destroying approximately 95 percent of the malignant tumor cells. In a second patient, following IL13-PE38 administration, radiographic scans of the brain revealed a significant reduction and disappearance in the size of the tumor, and the patient did not require a scheduled, additional, IL13-PE38 infusion. More recent findings will be presented at the upcoming Seventh Annual Meeting of the World Federation of Neuro-Oncology/Society for Neuro-Oncology (SNO) in San Diego on November 24th, 2002.

The second clinical study includes M.D. Andersen Cancer Center (MDACC), Memorial Sloan Kettering Cancer Center (MSKCC), the University of California San Francisco (UCSF) and Yale University as participating centers. Additional preliminary clinical data was recently presented at the Fifth Congress of the European Association of Neuro-Oncology (EANO).

In addition, enrollment has begun in the first global Phase I/II clinical trial of IL13-PE38; the third NeoPharm sponsored clinical study to date in patients with recurrent or progressive malignant glioma. The trial is being conducted at six participating sites including University Hospital Eppendorf and University Hospital Kiel in Germany, Chaim Sheba Medical Center and Dana Hospital Tel Aviv in Israel, Cleveland Clinic and University of Colorado in the United States. The trial's first cohort of three patients was enrolled in the first month of the study and enrollment is ongoing in the second cohort of patients.

For additional details regarding IL13-PE38 trial design, enrollment criteria and participating centers please refer to www.clinicaltrials.gov (keyword: IL13-PE38QQR).

About NeoPharm

NeoPharm, Inc., based in Lake Forest, IL, is a publicly traded biopharmaceutical company dedicated to the research, discovery and commercialization of new and innovative cancer drugs for therapeutic applications. The Company has a broad portfolio of compounds in various stages of development.

Additional information about NeoPharm and recent news releases can be obtained by visiting NeoPharm's Website at: www.neophrm.com . For copies of scientific abstracts related to IL13-PE38 from recent medical meetings, contact Lauren Greis, NeoPharm, at 847.295.8678.

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements include, but are not limited to, any statements relating to the Company's drug development program and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company's drug candidates, uncertainty regarding the outcome of damages claims made by or against the Company, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug candidates that could slow or prevent products coming to market, the uncertainty of patent protection for the Company's intellectual property or trade secrets and other risks detailed from time to time in filings the Company makes with the Securities and Exchange Commission including their annual reports on Form 10-K and their quarterly reports on Forms 10-Q. Such statements are based on management's current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release.

SOURCE NeoPharm, Inc.
-0- 11/07/2002 /CONTACT: Larry Kenyon, CFO of NeoPharm, Inc., +1-847-295-8678; or investors, Janet Dally of MontRidge, LLC, +1-203-894-8038; or media, Tricia Spellman of Outlook Marketing, +1-773-832-4047/ /Web site: http://www.clinicaltrials.gov http://mct.aacrjournals.org http://www.neophrm.com / (NEOL)


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