Disease is often localized to a particular region in the human body, yet the vast majority of our drug therapies expose the entire body to potentially harmful agents—as is the case with many cancer chemotherapeutic agents. Developing therapies that specifically target the site of disease, increasing a drug’s effectiveness while minimizing harmful side effects, is one of the goals of modern drug delivery technologies.

The goal of our drug delivery programs is to develop novel polymer products with the ability to deliver medicines in a targeted and controlled manner directly to the site in the body where they are required most. GLIADEL Wafer, intended for the treatment of brain cancer, is our first marketed product, but we are also developing new polymer products targeting a variety of other cancers

With our unique classes of biodegradable polymer products, Guilford is helping to advance the science of modern drug delivery by developing novel polymer drug delivery products for the treatment of cancer and other diseases. The specific purpose of Guilford’s polymer programs is to create products that administer treatment in a targeted and controlled manner. Because these products are site-specific, side effects are kept to a minimum, while efficacy is greatly enhanced. GLIADEL Wafer In 1996 the U.S. Food & Drug Administration granted permission to Guilford to commercially launch its first polymer-based product, GLIADEL Wafer for brain cancer. In 1997, in partnership with Rhône-Poulenc Rorer (RPR), Guilford made medical history by bringing to market the first and, to date, only cancer treatment capable of delivering chemotherapy directly to a tumor site. It represents the first significant advance in the treatment of brain cancer in two decades.    GLIADEL Wafer is currently approved for use in patients with recurrent glioblastoma multiforme, one of the most common and rapidly fatal forms of brain cancer. Once it is determined that surgery is an option for a patient, and after a tumor is surgically removed, up to eight dime-sized biodegradable GLIADEL Wafers are inserted into the tumor bed. As it degrades, GLIADEL Wafer emits a precise dosage of chemotherapy directly to the tumor site. Studies reveal that GLIADEL Wafer delivers 100 to 1,000 times more beneficial chemotherapy to a patient than standard methods of treatment. Moreover, GLIADEL Wafer complements other standard therapies for brain cancer, such as surgery, radiation and traditional intravenous chemotherapy, without the serious side effects associated with these treatments. To date, over 3,000 patients worldwide have benefitted from treatment with GLIADEL Wafer.    Already approved in nine countries, Guilford and RPR are focusing their efforts on continuing to make GLIADEL Wafer available to more patients worldwide. In 1999, we expect additional regulatory approvals in Europe. Additionally, we are continuing a multinational Phase III clinical trial to assess the survival benefit of GLIADEL Wafer when used at the time of first line therapy, with the goal of expanding the labeled indication for the product.

Ken Bonds Production Engineer

Polyphosphoester (PPE) Drug Delivery Program GLIADEL Wafer is only the first of a series of products Guilford hopes to commercialize for the controlled and targeted treatment of cancer. The Company is also developing an advanced class of polymer products called Polyphosphoester (PPE) polymers, which may have application in the treatment of several types of solid tumors, including ovarian, lung, breast, prostate and other cancers. Guilford’s biodegradable PPE polymers are being developed to allow delivery of anticancer medications directly to the site of a tumor for a sustained period of time. Guilford scientists and their collaborators have shown in preclinical experiments that PPE polymers can be used to deliver not only small molecules, but also larger molecules such as proteins, peptides and even genes. Moreover, they are adaptable to a wide range of formulations, including solid forms, gels, pastes, microspheres, liquids and films.    Like GLIADEL Wafer, Guilford’s PPE polymers can be formulated to offer drug delivery to the source of disease, offering the potential for improved efficacy while reducing drug exposure to the rest of the body. The first PPE polymer product moving towards commercialization is called PACLIMER™, a novel biodegradable polymer incorporating the chemotherapeutic agent paclitaxel (Taxol). Paclitaxel is one of the most successful anticancer products ever developed, and is currently used for the treatment of ovarian and other cancers. However, like most systemic anticancer drugs, it can have potentially significant adverse side effects. A safer, more effective form of this blockbuster drug could have tremendous market potential. PACLIMER™ will initially be studied for application in ovarian and lung cancer. DOPASCAN Injection We know that Parkinson’s disease is characterized by a loss of dopamine neurons in the brain, often severely compromising muscle control and movement. However, there are no FDA approved tests to diagnose or monitor the disease, the symptoms of which may mirror many other disorders. A Parkinson’s-specific test would enable earlier diagnosis and potentially better treatments and preventative measures.    Guilford is seeking to fill this void with its DOPASCAN Injection diagnostic test—a diagnostic and monitoring test specifically for Parkinson’s disease. DOPASCAN Injection is a radiopharmaceutical product under development that is intravenously injected and allows physicians to obtain pictures of dopamine neurons in the brain. DOPASCAN Injection may also be able to monitor the progression of the disease. Guilford has collaborated with Daiichi Radioisotope Laboratories (DRL) to develop and market DOPASCAN Injection in Japan, Korea and Taiwan.