Titan Pharmaceuticals Website
<http://www.titanpharm.com/>

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During the past year, Titan has made significant progress toward commercializing products for the treatment of schizophrenia, Parkinson's disease, cancer and other diseases. This progress can be measured by the advancement of several of our products into later-stage clinical testing, as well as the growing body of positive data which is accumulating regarding the safety and potential efficacy of these products.

Schizophrenia

In August 1998, Zomaril,™, Titan's product for the treatment of schizophrenia, advanced into Phase III clinical testing. This Phase III clinical program is supported by our corporate partner, Novartis Pharma, AG and will enroll 3,300 patients at 208 centers in 24 countries. Included in this program are several pivotal efficacy studies and long-term safety studies. Efficacy and safety of Zomaril will also be explored in special patient populations which include the elderly and patients with schizoaffective disorders. This unique, comprehensive clinical program is expected to confirm the role of Zomaril as a truly novel compound for the treatment of psychotic disorders. If the outcome of these studies is positive, Titan believes Zomaril will be positioned as first-line antipsychotic therapy, with low incidence of side effects such as extrapyramidal movement disorders, weight gain and sedation, that are seen with currently marketed antipsychotic drugs.

Cancer

In the cancer arena, Titan made important progress with several products. Two of our monoclonal antibody immunotherapy products, CeaVac™ and TriAb,™ advanced into Phase II clinical testing, as did our cell-differentiating agent, Pivanex™.

Currently, the Phase II study with CeaVac in colorectal cancer has enrolled more than 130 patients out of planned enrollment of 200, and the company is on target to complete accrual in 1999. The prestigious Journal of Clinical Oncology accepted for publication a paper describing the results achieved with CeaVac in a 32 patient Phase II study in colorectal cancer. As reported in this article, all 32 of these patients demonstrated vigorous and sustained humoral and cellular immune responses against CEA, an antigen present on colorectal cancer cells.

At the meeting of the American Society of Clinical Oncology (ASCO) held this past May in Atlanta, Titan announced important progress with its two additional therapeutic cancer vaccines, TriAb and TriGem.™ In results from an on-going Phase II clinical study of TriGem in patients with metastatic melanoma, it was reported that 40 of 47 patients generated strong, anti-cancer immune responses. Survival for this group of patients with advanced cancer compared very favorably to that seen in other historical studies with other anti-cancer drugs in this patient population. Preliminary results were also reported from an on-going Phase II clinical study with TriAb, in which consistent, strong immune responses against the breast cancer antigen HMFG were generated in metastatic breast cancer patients, despite decrease in their immune function following bone marrow transplantation.

Pivanex is progressing in Phase II clinical testing in patients with non-small cell lung cancer. In Phase I testing, Pivanex demonstrated anti-tumor activity in a patient with squamous cell lung cancer, and also demonstrated possible stabilization of disease, with improved performance status, in a patient with thymoma refractory to multiple therapies.

Titan's RB94 tumor-suppressor gene therapy has previously demonstrated significant anti-cancer activity in preclinical testing. To further advance this promising anti-cancer technology, Titan recently acquired rights to a tumor targeting delivery technology, which has the potential to allow intravenous or intra-arterial delivery of anti-cancer genes. Such an approach to systemic anti-cancer gene therapy may allow utilization in many additional cancer settings. Accordingly, Titan has launched additional preclinical studies in head and neck cancer and metastatic liver cancer. Such studies, if positive, could form the basis for fast track clinical development in high risk cancer settings urgently in need for improved therapy.

Parkinson's Disease

Spheramine™ is a cell-based therapy, which Titan is developing for treatment of Parkinson's disease. This product is comprised of normal, human cells, which are attached to microscopic beads. Spheramine is designed to be implanted into the brain of Parkinson's patients, where these cells will produce dopamine, to replace the dopamine which the patientÕs own neuronal cells can no longer produce. Over the past year, Titan made important progress with this product in preclinical studies by demonstrating in large scale primate testing that Spheramine is safe and effective at reversing symptoms in a validated primate model of Parkinson's disease. These results were presented in July at the XIII International Congress on Parkinson's Disease in Vancouver, which was chaired by Dr. Donald Calne, a scientific advisor to Titan's Spheramine program. Based on this important progress, the company plans to begin a Phase I/II clinical trial in 1999.

Drug Delivery System

Titan has also made significant advancements with its implantable drug delivery system. This product has the potential to be effective in numerous settings such as pain management and treatment of drug addiction. In NIH-sponsored preclinical testing, this product demonstrated proof-of-concept in animal models using an approved antipsychotic agent, which was delivered at sustained therapeutic levels for periods greater than three months, with no adverse side effects observed. Later this year, Titan plans to initiate a second NIH sponsored study, which will evaluate use of this product for treatment of drug addiction.


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Titan's Novel Treatment for Parkinson's Disease 

Spheramine™ is Titan's proprietary, cell-based therapeutic product for Parkinson's disease. Spheramine consists of cultured, dopamine-producing human retinal pigmented epithelial (RPE) cells, adhered to microcarriers which greatly enhance their survival when implanted into the central nervous system. This product is designed to produce dopamine in place of the patient's own neurons which can no longer perform this function. Spheramine may thereby be useful in restoring neurologic function previously lost in this degenerative disease.

Most Parkinson's patients are initially treated with drugs such as L-DOPA, which supply a precursor of dopamine that is converted to dopamine in the brain. This approach becomes less effective over time as increasing numbers of neurons die. Various forms of surgical intervention have been attempted to address this unmet medical need, including cell transplants involving human or pig fetal dopamine producing tissue. Titan believes Spheramine offers several potential advantages over each of these approaches.

With fetal human and pig cell transplants, there is controversy surrounding the availability, uniformity and source of the cells, as well as problems regarding their survival and the need for immunosuppression. These issues can potentially be eliminated with Spheramine, which consists of microscopic beads that are coated with normal, human RPE cells. The cells are readily available and can be manufactured in large numbers using cell culture techniques. It is estimated that cells from a single human donor can be cultured and expanded to potentially provide treatment for thousands of Parkinson's patients. Survival of these RPE cells is greatly enhanced by Titan's patented CCM™ technology, which provides a bead matrix to which the cells attach and grow, and eliminates the need for immunosuppression.

Preclinical efficacy and safety studies with Spheramine in a validated primate model of Parkinson's disease have recently been successfully completed. Based on these encouraging studies, Titan plans to initiate Phase I/II clinical trials with Spheramine in 1999. If effective, Spheramine could offer Parkinson's patients the opportunity for long-term restoration of neurologic function and reduce or eliminate the need for conventional drug therapies.

Long-Term Drug Delivery System

In the CNS arena, Titan is also developing a drug delivery system, which may potentially provide controlled drug release over extended periods (i.e., from three months to one year). This platform technology involves imbedding the drug of interest in a co-polymer, which is then implanted subcutaneously to provide systemic delivery. This results in a constant rate of release similar to intravenous administration, which avoids the peak and trough level of oral dosing that causes problems for various therapeutic agents.

This technology offers significant potential benefits to patients suffering from chronic CNS disorders, such as Parkinson's disease, Huntington's disease, schizophrenia, psychosis, drug addiction and chronic pain, by providing long-term, intravenous type dosing in a single administration. Titan is currently conducting preclinical research with this technology, and previously announced that proof of principle has been demonstrated in a pilot animal study in which this drug delivery system delivered an antipsychotic drug at therapeutic levels in a constant, sustained fashion for over three months.

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janet paterson
52 now / 41 dx / 37 onset
613 256 8340 po box 171 almonte ontario canada K0A 1A0
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