Titan's Proneura Technology Prevents Onset of Motor Complications In Validated Parkinson's Disease Model
Wednesday November 12, 8:34 am ET
Data presented at the Society for Neuroscience 33rd Annual Meeting

SOUTH SAN FRANCISCO, Calif., Nov. 12 /PRNewswire-FirstCall/ -- Titan Pharmaceuticals, Inc. (Amex: TTP - News) today
announced positive preclinical results demonstrating that continuous drug delivery using the Company's ProNeura(TM)
technology reduced the risk of motor symptoms in a validated primate model of Parkinson's disease. The study results
were presented today in New Orleans at the Society for Neuroscience 33rd Annual Meeting.

Parkinson's disease is characterized by the gradual degeneration of dopaminergic neurons in the brain, and resulting
lower levels of dopamine in specific brain regions (the striatum). This lack of dopamine is currently treated in
Parkinson's patients by the oral administration of levodopa or other dopamine agonists. While these agents are both
safe and effective at early stages of treatment, over time most patients begin to develop side effects known as motor
complications. The more common complications include involuntary movements (dyskinesias) and a progressive shortening
of benefit time after dosing (wearing off fluctuations).

There has been indirect evidence that these motor complications are not caused by levodopa itself, but by the way it is
administered. Under normal conditions, there is constant production of dopamine by certain neurons in the brain, which
results in stable levels of dopamine in the striatum. In Parkinson's disease, the loss of neurons that provide dopamine
to the striatum reduces this stable dopamine signal. Treatment with levodopa pills results in fluctuating dopamine
levels, which are high immediately after administration, and then low several hours after dosing, causing significant
cyclic changes in dopamine levels. Researchers have hypothesized that these cyclically varying levels of dopamine from
oral administration contribute to the onset of motor complications. However, the theory that such varying dopamine
levels is a cause of motor complications has never been demonstrated directly, largely because of the difficulty in
maintaining constant levels of dopaminergic drugs in animal models or patients for a sufficiently long time to evaluate
the development of motor complications.

As described in the study results presented today, Titan's ProNeura technology allowed the direct testing and initial
confirmation of this hypothesis in a validated primate model of Parkinson's disease, the MPTP model.

Titan's ProNeura technology is a copolymer based implant into which a therapeutic drug is incorporated. The implant is
placed under the skin, allowing the drug to be delivered appropriately at a consistent level over an extended period.

In this study, researchers at Titan and the National Institutes of Health (NIH), under the direction of Dr. Thomas N.
Chase, Chief of Experimental Therapeutics Branch of NINDS/NIH, compared constant administration of a dopaminergic agent
using ProNeura technology, to once daily administration, for a period of six months. The drug chosen was apomorphine,
which has a similar pharmacological profile to levodopa.

Results showed that the initial therapeutic response from daily apomorphine injections was comparable to that from
Titan's ProNeura implant containing apomorphine. However, after approximately two weeks of daily apomorphine treatment,
animals in the daily treatment group developed significant motor complications (dyskinesias). In the continuous
treatment ProNeura group, no dyskinesias or any other motor complications developed for the entire six month duration
of treatment.

"These results suggest that this delivery system can overcome the potential side effects of standard dosing regimens to
provide a better treatment for Parkinson's disease," said Dr. Thomas N. Chase, Chief of Experimental Therapeutics
Branch of NINDS/NIH, and principal investigator for the study. "This method of releasing a steady and constant amount
of dopamine agonists is the first of its kind and represents an important step towards improving the quality of life of
Parkinson's patients."

Titan's ProNeura technology utilizes an ethylene vinyl acetate (EVA) copolymer that forms a matrix in combination with
the drug to be administered. The matrix is then made into a small flat rod that is placed under the skin, allowing
consistent drug levels to be maintained in the blood for up to six months after a single administration, avoiding the
varying blood levels often seen with daily drug administration. Replacement of the matrix after six months can
potentially continually extend treatment.

"These results are encouraging," stated Louis R. Bucalo, M.D., Chairman, President and CEO of Titan, "and provide a
potential expansion of Titan's continued commitment to improved treatment of Parkinson's disease. These results with
apomorphine demonstrate proof of principal of the potential utility of continuous administration of dopamine agonists
in earlier stages of Parkinson's disease using ProNeura technology. Our next steps are to evaluate the possible
suitability of various dopamine agonists for incorporation into our ProNeura technology."

About Titan Pharmaceuticals

Titan Pharmaceuticals, Inc. (Amex: TTP - News) is a biopharmaceutical company focused on the development and
commercialization of novel treatments for central nervous system disorders, cancer and cardiovascular disorders.
Titan's numerous products in development utilize novel technologies that have the potential to significantly improve
the treatment of these diseases. Titan also establishes partnerships with multinational pharmaceutical companies and
government institutions for the development of its products.

The press release may contain "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 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, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug candidates that
could slow or prevent product development or commercialization, the uncertainty of patent protection for the Company's
intellectual property or trade secrets and the Company's ability to obtain additional financing if necessary. 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: Titan Pharmaceuticals, Inc.

SOURCE: Yahoo News (press release)
http://biz.yahoo.com/prnews/031112/nyw109_1.html

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