Mammastatin For Detecting And Treating Breast Cancer

Biotherapies Incorporated is a cancer research and development company dedicated to finding new and improved cancer therapies and diagnostics to improve the quality of life and prognosis for cancer patients worldwide. The current platform product-concept centers on Mammastatin as a major medical breakthrough in the diagnosis and treatment of breast cancer. Recent research suggests that similar proteins in other, frequently cancerous, tissues perform the same role Mammastatin plays in breast tissue. It is anticipated, therefore, that a full line of "natural" growth inhibitory, protein-based products will be developed to treat and diagnose the full range of human cancers. Our first product, the Mammastatin Serum Assay (MSA), has been licensed to Biomedical Diagnostics LLC, which we recently sold for $14M with a 10-20% royalty on net revenue. The Company has three products that work together to provide a comprehensive strategy for breast cancer detection and treatment: (1) Mammastatin Replacement Therapy - An intravenous injection of Mammastatin administered to a breast cancer patient every one to three days to restore Mammastatin levels to those found in healthy women. This drug product is currently part of a clinical testing program. Product launch is expected within two years. (2) Mammastatin Serum Assay (MSA) - A blood test to measure Mammastatin levels in the blood, administered as part of a woman's routine annual physical examination or to monitor the effectiveness of replacement therapy. The laboratory uses the MSA test kit to detect and quantify Mammastatin levels. Biomedical Diagnostics LLC was created to develop the MSA. Biotherapies has recently sold its interest in Biomedical Diagnostics for $14M with a 10-20% royalty on net revenue. (3) Mammastatin Diagnostic Assay (MSA) - A biopsy test to confirm breast cancer diagnosis. This product would be used by a pathologist to confirm a diagnosis of breast cancer following mammography. Currently, additional studies are being pursued to determine whether this is effective from needle aspirate samples, as well as excisional biopsy samples. This product will launch this year.

Future Products Pending the results of the Phase II FDA clinical trial, the Company will conduct developmental research on other Mammastatin products such as the following: (1) Alternate Therapeutic Delivery - A nasal spray or inhaler, implant, pump, necessary for prevention use. (2) Alternate Diagnostic Formats - A disposable kit for individual home use (similar to pregnancy test kit), and format for automated instrumentation in large laboratories. Will be developed by Biomedical Diagnostics and will fall under licensed technology. In addition, the Company is conducting research on other inhibitory proteins to potentially diagnose and treat cancers of other epithelial tissues, such as ovarian, prostate, pancreatic, colon, melanoma, and lung cancer.

©1999-2001. Biotherapies, Inc. All Rights Reserved Worldwide.

Overview

Biotherapies Incorporated is primarily a research and development company. The company initially focused on further description of technology identified and developed by Dr. Paul Ervin at the University of Michigan. This technology involves using the human protein, Mammastatin, as a breast cancer therapy and techniques to identify this protein. Identification and measurement of the protein can be used as tests to identify breast cancer and determine breast cancer risk. Both of these applications for Mammastatin have been successfully developed by the research team at Biotherapies.

 

• Mammastatin protein has been the subject of a clinical trial at the MD Anderson Cancer Center in Houston, Texas. This trial, a Phase I, Maximum Tolerated Dose Study, enrolled 19 patients. Compassionate use of Mammastatin was instituted in 1996 for a select group of late--stage breast cancer patients. Results from the compassionate use of Mammastatin in the United States and Canada (38 patients) have been very encouraging.

   

   

• The Mammastatin Serum Assay^TM has been developed as a method to identify breast cancer risk. Preliminary results with serum samples from over 500 women have suggested that Mammastatin is lacking in most patients with breast cancer. Women from high risk families also lack serum Mammastatin. About 15% of the rest of the women tested had low or undetectable levels of Mammastatin. Current data suggests that these 15% represent the population at risk to develop breast cancer.

   

Additional research investigations have involved the following:

• Determining the mechanism of action of Mammastatin
• Cloning the gene for Mammastatin
• Developing other formats for the Mammastatin diagnostic assay
• Developing systems for expression of recombinant Mammastatin
• Finding proteins related to Mammastatin that might be effective for other cancers
• Determining alternative effective delivery methods for Mammastatin

©1999-2001. Biotherapies, Inc. All Rights Reserved Worldwide.

Mammastatin Therapy

• A protein produced by the body of healthy women
• Blocks breast cell growth
• Isolated from normal breast tissue and in blood drawn from healthy women
• Missing in most (over 90 percent) breast cancer patients
• Capable of stopping the growth of breast cancers
• Non-toxic and only affects breast cancer cells

As a therapeutic, the Mammastatin protein, in a saline solution, is injected into the bloodstream of breast cancer patients on a daily basis to restore levels to those found in healthy women, similar to insulin injection for diabetics. Under compassionate therapy programs in both the United States and Canada, pre-clinical tests were conducted on 34 late stage breast cancer patients who were no longer responsive to chemotherapy. In these tests, the therapy was found to be as follows:

 

• Effective in stopping the breast cancer cell growth in over 70% of cases - including breast cancer cells metastasized to other tissues (lymph, bones, liver, brain, lung (in order of responsiveness).

   

   

• Effective in causing complete remission in about 15% of the cases (5 of 34 patients).

   

   

• To cause no adverse side effects or toxicity, unlike other cancer treatments.

   

   

• To result in greatly increased quality of life.

   

In each case where patients have received treatment, the patient had significant metastasis to other tissues, and life expectancy of less than two months. The replacement therapy was administered daily without interfering with other therapies the patient might be using. A few patients received continuous treatment for almost four years before treatment was stopped. Most of the patients who have been taken off of Mammastatin therapy have died. This data suggests that continuous Mammastatin will be shown to be safe alone, with chemotherapy and with hormone therapy. It also points out that Mammastatin does not cure the cancer, but controls it. Long-term therapy will be necessary. The exciting news is that Mammastatin allows the patient to remain alive long enough for "long-term" to be an option and that the product is expected to be even more effective in treating earlier stages of breast cancer.

©1999-2001. Biotherapies, Inc. All Rights Reserved Worldwide.

Clinical Trials

Phase I Study
A Safety and Dose Finding Study for Native Mammastatin began in June, 1999, at MD Anderson Cancer Center. The Principal Investigator for the study is Dr. Francisco Esteva. The indication for which the therapy is being evaluated is Refractory Stage IV Breast Cancer. The primary objectives of the study are as follows:

• To evaluate the safety of native Mammastatin at various dose levels
• To determine the Maximum Tolerated Dose (MTD). The starting dose is 19 mg/m2. Dose escalation will be done by 100% increments. Therefore, the five doses are 19,38,76,153, and 307 mg/m2. Six patients will be enrolled per dose cohort. Once the MTD is determined, at least six additional patients will be studied at the MTD.

  Secondary objectives of the study are to collect preliminary efficacy data for Native Mammastatin.

  Result: This study was halted after recruitment of 19 patients (three dose levels) in February 2000. Although no adverse events were reported and no toxicity was identified for the drug product, a contamination of product was identified. This contamination event interrupted drug supply for a critical period, making it necessary to close the trial. Of the 19 patients tested, there were two patients that experienced significant improvement. There were no reports of toxicity for any patient.

  Future Clinical Trials
  Over the past four years, Native Mammastatin has been given to patients on a compassionate basis. Preliminary observations indicate that there may synergy between Mammastatin therapy and estrogen antagonists (such as Tamoxifen). This synergy will be further evaluated in further Phase I and Phase II clinical trials. Additional Phase I trials are being planned. In addition, a multi-center trial is being designed to evaluate the response of the combination therapy in both estrogen-receptor positive and estrogen-receptor negative patients with refractory breast cancer. The study will be performed at Peace Arch Hospital, Cancer Control Agency, Vancouver, British Columbia; MD Anderson Cancer Center; and UCSF Cancer Center. Biotherapies, Inc. is in the process of finalizing the protocol and the procedural details with the trial site. The study proposal and the IND application will, then, be submitted to Health Protection, Canada, and the FDA for approval.

  There are currently no active Mammastatin trials.

©1999-2001. Biotherapies, Inc. All Rights Reserved Worldwide.