Exhibit 20.1
TITAN PHARMACEUTICALS, INC. LETTERHEAD
Company: Media: Investors:
Robert Farrell Mark Padgett Dawn Lauer
Executive Vice President & CFO GCI Group GCI Group
650-244-4990 212-537-8082 212-537-8088
FOR IMMEDIATE RELEASE
TITAN ACQUIRES NOVEL AGENT IN CLINICAL TESTING FOR
THE TREATMENT OF CONGESTIVE HEART FAILURE
SOUTH SAN FRANCISCO, CA - OCTOBER 16, 2003 - Titan Pharmaceuticals, Inc.
(ASE:TTP) announced today that it has acquired a novel product in clinical
testing for the treatment of congestive heart failure. The product in
development, 3,5-diiodothyropropionic acid, is an orally active analogue of
thyroid hormone that has demonstrated in preclinical and clinical studies to
date the ability to improve cardiac function, with no significant adverse
effects. Beneficial effects demonstrated in these studies include improved
cardiac output, as well as improvement in measures of diastolic function. In
addition, 3,5-diiodothyropropionic acid, or DITPA, has also demonstrated
significant cholesterol and triglyceride lowering capability in pilot clinical
testing.
Titan plans to develop DITPA as a potential treatment for congestive heart
failure (CHF), and also will evaluate its potential use as a treatment for
patients with significantly elevated cholesterol and triglyceride levels.
DITPA has completed Phase I and preliminary controlled Phase II testing, and
will begin a randomized, double blind Phase II clinical study in patients with
CHF in the next few months. This multicenter study is funded by a $3.8 million
government grant from the federal Veterans Administration (VA) system.
Congestive heart failure (CHF) is a syndrome of progressive decrease in cardiac
function and inability of the heart to pump sufficient blood for proper function
of the lungs, kidneys, and other vital organs and tissues. Symptoms include
decreasing activity capacity, shortness of breath, and peripheral and pulmonary
edema. There are a total of approximately 9 million people in the U.S. and
Europe with CHF. In the U.S., approximately 30% of patients have moderate or
severe symptoms (New York Hospital Association Class III or IV), and CHF is the
most common hospital discharge diagnosis in the U.S. for patients over 65.
Currently, only approximately 50% of patients diagnosed with CHF survive for
five years, and only 50% of patients with class IV CHF survive one year. New
treatments for CHF are greatly needed to improve symptoms, enhance cardiac
function, and avoid dangerous and progressive complications of congestive heart
failure.
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Current treatments for congestive heart failure include angiostensin converting
enzyme (ACE) inhibitors and diuretics that act to reduce fluid volume load, and
beta-blockers.
DITPA represents a potential new class of agents for CHF, based upon the central
role of thyroid hormone in regulating cardiovascular function.
Scientists have previously recognized the important cardiovascular actions of
thyroid hormone and its potential beneficial effects on the heart and peripheral
blood vessels. In fact, thyroid hormone itself is currently used in the acute
post-surgical hospital setting to support the heart after cardiopulmonary bypass
in heart surgery patients.
Thyroid hormone is known to have numerous effects on the heart and blood
vessels, including decreasing arterial and venous resistance, increasing venous
return to the heart, and increasing the effectiveness of cardiac contraction.
Collectively, these actions are believed to be potentially beneficial in
patients with CHF. Thyroid hormone itself, however, also significantly increases
heart rate, and this effect is undesirable in patients with CHF.
DITPA is a thyroid hormone analogue that was synthesized and selected based upon
its ability to significantly improve cardiac function in experimental models of
heart failure without significantly increasing heart rate. Specifically, when
DITPA was administered alone or in combination with captopril in animal models
of heart failure, cardiac output was improved and left ventricular end diastolic
pressure was decreased, without significantly increasing heart rate. In
addition, DITPA improved the time for ventricular relaxation, indicating a
beneficial effect on diastolic function. (1)
DITPA has demonstrated similar potentially beneficial effects in preliminary
human testing. A double-blind, placebo controlled Phase II study in 19 patients
with moderately severe (NYHA Class II-III) heart failure demonstrated a
significant improvement in cardiac index, a significant decrease in systemic
vascular resistance, and no significant increase in heart rate. These study
results also supported a beneficial effect of DITPA on diastolic function. (2)
In addition, results from this study as well as previous preclinical testing
suggest that DITPA is compatible with other current treatments such as ACE
inhibitors.
In addition to the above positive effects on cardiovascular function, patients
receiving DITPA in this study also demonstrated an approximate 24% reduction in
serum cholesterol, as well as a 35% reduction in triglycerides over the course
of the 4 week study. Given that coronary artery disease is a major cause of
congestive heart failure, the Company believes this lipid lowering activity may
be a useful and novel property of DITPA in the treatment of CHF. This property
may also be useful in the treatment of patients with isolated significant
hyperlipidemia.
Based upon the favorable initial results of clinical testing, DITPA has received
a $3.8 MM grant from the Department of Veterans Affairs Cooperative Studies
Program to fund a 150 patient, double blind, placebo controlled Phase II study
in patients with moderately severe CHF, which is scheduled to commence in Q1
2004.
Titan acquired DITPA through the acquisition of Developmental Therapeutics, Inc.
(DTI), a private company established to develop DITPA, and the exclusive
licensee of recently issued U.S. and pending international patent applications
covering DITPA. Titan acquired DTI in an all stock transaction for 1,187,500
shares of Titan common stock, and made a cash payment of $171,250 to the
licensor of the technology. An additional payment of 750,000 shares of Titan
common stock will also be made upon the achievement of positive pivotal study
results or certain other similar substantial milestones.
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"We are very pleased to acquire this novel agent in development for congestive
heart failure," stated Dr. Louis R. Bucalo, Chairman, President and CEO of
Titan. "DITPA represents a potentially new approach to treatment with a novel
mechanism of action."
An expert advisory group has been established to help guide the further
development of DITPA, including Dr. Jay Cohn, Professor of Medicine,
Cardiovascular Division, Department of Medicine at the University of Minnesota;
Dr. Milton Packer, Dickinson W. Richards Jr. Professor of Medicine, Professor of
Pharmacology, Chief of the Division of Circulatory Physiology at Columbia
University, College of Physicians and Surgeons and Director of the Heart Failure
Center at the Columbia-Presbyterian Medical Center in New York City; Dr. Paul
Ladenson, Professor of Medicine, Director of the Division of Endocrinology &
Metabolism at John Hopkins School of Medicine; Dr. Eugene Morkin, C. Leonard
Pfeiffer Professor of Medicine, Co-Director Sarver Heart Center, University of
Arizona Health and Sciences Center; and Dr. Steven Goldman, Professor of
Medicine and Surgery, Chief of Cardiology, Southern Arizona VA Healthcare
System.
"DITPA represents a potentially significant advance in the treatment of
congestive heart failure because of its broad spectrum of activity on the heart
and peripheral vasculature," stated Dr. Eugene Morkin, C. Leonard Pfeiffer
Professor of Medicine, and Co-Director, Sarver Heart Center, University of
Arizona Health and Sciences Center. "The ability of DITPA to potentially improve
cardiac output without increasing heart rate is very promising. This unique
physiological mechanism of action places DITPA in a new class of therapy for the
treatment of this disease."
ABOUT TITAN PHARMACEUTICALS
Titan Pharmaceuticals, Inc. (ASE: TTP) is a biopharmaceutical company focused on
the development and commercialization of novel treatments for central nervous
system disorders, cancer and other serious and life-threatening diseases.
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.
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REFERENCES
(1) Morkin E, Pennock G, Spooner P, Bahl J, Goldman S. Clinical and Experimental
Studies on the Use of 3,5-Diiodothyropropionic Acid, a Thyroid Hormone Analogue,
in Heart Failure. Thyroid 2002:12(6):527-533.
(2) Morkin E, Pennock G, Spooner P, Bahl J, Underhill Fox K, Goldman S. Pilot
Studies on the Use of 3,5-Diiodothyropropionic Acid, a Thyroid Hormone Analog,
in the Treatment of Congestive Heart Failure. Cardiology 2002:97:218-225.
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