BioSyntech Inc.: A Novel Non-Toxic Sustained Release Taxol Formulation for Cancer Chemotherapy.

Business Editors & Health/Medical Writers

LAVAL, Quebec--(BUSINESS WIRE)--Sept. 17, 2002

BioSyntech Inc. (OTC BB:BSYI ). The Therapeutics Delivery division at BioSyntech today announced the results of its pre-clinical efficacy studies using Pacligel (a unique sustained release formulation of paclitaxel based on BioSyntech's platform BST-Gel technology) on human breast tumor model (MCF-7) implanted orthotopically into immuno-compromised SCID mice's mammary fat pad (mfp) as well as a distant subcutaneous location. This work was conducted at the Lady Davis Institute of the Jewish General Hospital, McGill University.

The potential of current systemic chemotherapy for cancer is limited by normal tissue toxicity. Several approaches have been developed to overcome this problem, ranging from the use of liposome encapsulated drugs, prodrugs that can be activated selectively in specific tumor tissue, etc. Most of these approaches have revealed several disadvantages including high costs, and have had very limited success clinically.

Paclitaxel is a hydrophobic drug and is the active ingredient in Taxol, a cancer drug with worldwide sales in excess of $2.4 billion US in 2000. To aid its dissolution, Taxol contains a cremophor, a toxic substance which causes severe hypersensitivity and allergic reactions and in some cases leads to anaphylactic shock. To overcome the toxicity of the cremophor, long infusions typically are required to administer Taxol to cancer patients.

Dr. Ajay Gupta, Executive Vice-President, Therapeutics Delivery at BioSyntech Inc. commented: "Our Gel based formulation does not contain any cremophor or any organic solvent and we believe that it has the potential to overcome the limitations of Taxol currently administered intravenously. A sustained delivery of paclitaxel based on our BST-gel technology has various advantages including minimal systemic exposure of the chemotherapeutic agent that could potentially reduce or eliminate commonly observed side effects of Taxol such as vomiting, vertigo, cachexia, cardiotoxicity, neurotoxicity etc. These side effects often interrupt treatment schedules. Our Pacligel product is safe and has a very good potential for becoming the paclitaxel based chemotherapeutic agent of choice for the treatment of various cancers. Additional chemotherapeutic drugs such as camptothecin have been encapsulated into BST-Gel and in-vivo experiments are currently underway at Montreal General Hospital, McGill University to evaluate the potential of our new camptothecin-BST-Gel formulation for the treatment of glioblastomas."

In the pilot breast cancer study conducted at Lady Davis Institute, McGill University, the animals were randomized into several groups: untreated, treated with empty vehicle, free Taxol given intra-peritonially (i.p.), or Pacligel administered into the mammary fat pad. Pacligel doses ranging from 40mg/kg to 320 mg/kg were implanted into the mammary fat pad of the mice and the tumor volumes were measured as a function of time. Tumor growth was monitored over a period exceeding 2.5 months. A dose response in the inhibition of tumors growing in the mammary gland was clear with the gel encapsulated formulations showing over 50-60% inhibition of tumor growth with just a single dose, which was maintained even after 80 days. More exciting was the inhibitory effect of the local mfp implanted Pacligel on the growth of mammary tumors implanted at a distal subcutaneous site. Compared to the free Taxol administered i.p., the Pacligel didn't show any signs of systemic toxicity, no loss in the body weight of animals was observed and there were no fatalities or other adverse effects observed at either of the 40 mg/kg, 80 mg/kg or 320 mg/kg dose levels. However, free Taxol when administered i.p. into the mice, showed an acute toxicity at 40 mg/kg and 80 mg/kg doses with an initial loss of body weight. The 160 mg/kg free Taxol dose when administered i.p. into the mice, was found to be lethal.

The tumors in animals treated with free Taxol started to grow on a new and relatively steeper growth curve from day 37 onwards compared to the ones treated with Pacligel. It is understandable based on the half life (t1/2) of about 6 hours for the free Taxol. This would mean that in about 3.5 days, more than 99.99% of the free Taxol would have been cleared from the systemic circulation in the body and the residual tumor cells would start to regrow in the absence of any chemotherapeutic agent.

There was a significant delay in the growth of subcutaneous tumors for all the Pacligel groups, giving a good indication that the free Taxol was getting released from Pacligel and entering into the systemic circulation in a safe fashion i.e. giving systemic exposure at very low concentrations of free Taxol.

It is important to note that Pacligel not only showed efficacy, but was also found to be quite safe at twice the lethal dose of the free Taxol.

Dr. Moulay A. Alaoui Jamali, a well known cancer pharmacologist at Lady Davis Institute, McGill University, and the principle investigator of the Pacligel study commented "The above results indicate that there is an increase in the therapeutic index of Taxol. Pacligel is truly an exciting and very promising product to improve paclitaxel efficacy for cancer as it has been found to be non-toxic at dose levels 8 times higher than the maximum tolerated dose (MTD) of free Taxol in humans. Additionally, due to the slow and sustained release of Taxol at concentrations that are able to target distant disease, the Tumor Growth Delay (TGD) at the distal subcutaneous site is significant compared to free Taxol administered i.p. This new product could revolutionize cancer chemotherapy including the treatment of metastatic tumors."

More in-vivo experiments are currently underway. Shortly, in-vivo pre-clinical experiments will be set-up to evaluate the potential of Pacligel to treat metastatic breast tumors and prostate cancer.

About BioSyntech

BioSyntech Inc. is an ISO 9001:2000 certified, advanced biomaterials company specializing in tissue repair and in the delivery of therapeutic products. BioSyntech is composed of two operating divisions: tissue repair and therapeutic delivery. The Company's patented platform technology BST-Gel(TM), is a multifunctional injectable thermo-sensitive and self-forming hydrogel that can be used for tissue repair or for targeted delivery of therapeutic agents. These biomaterials are biocompatible, biodegradable, muco adhesive and provide significant advantages in specialized medical fields including, Oncology, Orthopedics, Rheumatology, Reconstructive Surgery, Tissue Engineering, Vaccines and many other therapeutic areas. For additional information, visit www.biosyntech.com.

This press release contains certain "forward-looking" statements, as defined in the United States Private Securities Litigation Reform Act of 1995 that involve a number of risks and uncertainties. There can be no assurance that such statements will prove to be accurate and the actual results and future events could differ materially from management's current expectations. Potential risks and uncertainties include timeframes and expectations for completing clinical trial research, receiving positive results from the various clinical trials, submitting results to various regulatory authorities, receiving approval for products and successfully marketing products to potential customers. These risks and factors are detailed from time to time in the company's SEC filings.