Endovasc Discovers Dose for Inhibition of Smooth Muscle Cell Migration and Restenosis; Company Accelerates Two Studies to Prove its Drug-Coated Stent Prevents Restenosis.

Business Editors & Health/Medical Writers

MONTGOMERY, Texas--(BUSINESS WIRE)--Jan. 9, 2003

Endovasc Ltd. Inc. (OTCBB:ENVC) - a biotechnology company focused in the area of cardiovascular disease - announced today that it had discovered the effect dose of prostaglandin E-1 (PGE-1) that inhibits the migration of smooth muscle cells (SMCs) - believed to be the culprit cells that produce restenosis in angioplasty and stents. A confirmation study is scheduled to begin at the Armed Forces Institute of Pathology (AFIP) in Washington, D.C. within a month that will involve a repeat of the in vitro discovery and a second in vivo study in a rabbit model. The Company stated that Guidant Corp's (NYSE:GDT) announcement that it had abandoned its $3 billion plan acquiring Cook Inc. for its paclitaxel drug-coated stent represents a major market opportunity for Endovasc. Guidant's cancellation of the proposed acquisition due to failure of the drug coating means a reduction in the number Endovasc's strong competitors down to just two: Johnson & Johnson (NYSE:JNJ) and Boston Scientific Corp. (NYSE:BSX).

According to U.S. Bancorp Piper Jaffray, drug-coated stents are estimated to account for 92 percent of the overall stent market in 2005, which is estimated to reach $5 billion. Endovasc believes it could bring its drug-coated stent to market as early as in 2004, subject to the regulatory approval process. In comparison, it will be at least 2005 before Guidant will have a drug-coated stent available for market, first in Europe (source: Reuters 1/3/03, 6:07pm ET).

Endovasc has patented an exclusive technology for coating vascular stents. A stent is a device used in conjunction with angioplasty procedures; serving as a scaffold to prevent newly expanded arteries that have been cleared surgically, from collapsing. However, as many as one-third of all non-drug coated stent procedures currently result in re-clogging, i.e. restenosis.

"The key to our discovery was finding the drug's action is bi-phasic," said Chairman and CEO, Dr. David Summers, "at a certain dose the drug simply shuts down SMC migration by elevating cyclic adenosine monophosphate (cAMP) which modulates the G-protein pathway arresting cell migration by causing dose-response retraction of the cells microtubule pods. The cell then cannot migrate, " he said.

Endovasc's PROStent(TM) is a stent coated with Liprostin(TM), Endovasc's prostaglandin (PGE-1) based treatment. Endovasc has already filed an IND application with the FDA for its Liprostin(TM) drug and is expected to start its Phase III trials with the drug early this year, upon the completion of a pilot study conducted at University of Texas-Memorial Hermann Hospital in Houston, slated to begin next week.

Endovasc said it first tested the drug at high (1000-fold greater) doses in stents implanted in pigs at St. Louis University Hospital. "We thought more was better," said Summers. "Although we saw very little to no inflammatory response, the high dose caused the SMCs to secret proteoglycans producing moderate hyperplasia. We discussed the response with the world-renowned prostaglandin expert, Dr. David Horribin in England and he pointed us to two recent articles that demonstrated the bell-shaped curve effect. The lowered dose to 10(-6)M produced complete migratory inhibition," he said.

"In order to independently reconfirm the anti-restenosis dose, we will repeat the experiment in vitro in Dr. Renu Viramani's laboratory, then implant stents in two groups of rabbits maintaining the effective blood-plasma levels for one month in one group and one month in a control group with bare stents and no drug. The studies should start within the next 2-3 weeks and be completed in approximately 4-6 weeks," describes Dr. Summers.

He said, "Dr. Viramani's team performing the study consists the same people who conducted research for Johnson & Johnson's (JNJ) anti-restenosis drug, Sirolimus(TM), the only successful drug in this category on the market thus far. We believe this group has the best background and knowledge to execute this important milestone study for us. The repeat of our dish study should take only days to complete."

Endovasc has other stent related products. In November, Endovasc and MIV Therapeutics (MIVT) of Vancouver B.C. announced the formation of Stentgenix, Inc., a 50/50 joint venture company which will focus on developing Endovasc's other drug, Angiogenix(TM) in a breakthrough pharmaceutical coating on MIVT's stents to block restenosis while stimulating angiogenesis (new blood vessel growth in the patient's heart or limbs) for both coronary and peripheral stents. MIVT agreed to invest $2.5 million in the new company. If successful, this new development could enable interventional cardiologist, interventional radiologist, and vascular surgeons trained in catheter procedures, anywhere in the world to use stents to promoted new blood vessel growing therapy for many forms of heart and vascular disease in conjunction with well know common angioplasty procedures.

Stentgenix is also developing Endovasc's next generation of biodegradable/resorbable stent and catheter accessory technologies. "We already have prototypes," said Summers, "and this could become truly the next platform of mechanical interventional/drug technology with myriad potential uses from local cancer drug delivery, to temporary urethral and ureteral stents and shunts capable of maintaining a patent tract while releasing temporary local drug treatments (such as Hytrin) for such procedures as post transurethral resections (TUR), lithotripsy, and remodeling treatments for various tracts, ducts, and vessels.

About Endovasc

Endovasc's pending Phase III products include ANGIOGENIX(TM), a potent small molecule that uniquely uses the acetylcholine receptor agonist (nAChR) pathway shown to stimulate DNA synthesis and upregulate growth factors such as vascular endothelial growth factor (VEGF) transforming growth factor (TGF)-1 basic fibroblast growth factor (bFGF) and various essential adhesion molecules such as VCAM-1 necessary for angiogenesis. The drug has also demonstrated recruitment and local mobilization of adult stem cells to ischemic injury sites and is a survival factor for endothelial cells under oxygen deprivation (hypoxia) possibly offering a new therapy for myocardial apoptosis, which is the premature death of heart muscle cells.

The Company believes that Angiogenix(TM) will become the first successful angiogenic agent. The growth of new blood vessels in the heart is aimed at ameliorating ischemia and reducing chronic angina (chest pain) while improving heart function via the process providing new blood supply. The company's other pending Phase III product is Liprostin(TM), a naturally occurring liposomal prostaglandin-based treatment that recent studies suggest may prevent restenosis (re-blockage of arteries), without stents, increasing circulation, and reduce leg pain due to poor blood flow, and accelerate healing of stasis wounds and bed sores. Each of these products has market potential of over $1 billion annually.

Endovasc Ltd., Inc., established in 1996, is a biotechnology company focused in the area of cardiovascular disease, pioneering drug delivery technology designed to deliver and release drugs to their intended targets in an efficient and controlled manner. The company's products and processes include Liprostin(TM), ANGIOGENIX(TM) (Nicotine Receptor Agonist), PROStent(TM) stent-coating technology, and biodegradable resorbable prostheses.

The foregoing statements are made under the "Safe Harbor" Private Securities Litigation Reform Act of 1995 and may contain forward-looking statements that involve risks and uncertainties that may not be evident at the time of this release. For more information about Endovasc, please visit www.endovasc.com. (Investor questions and requests for materials can be submitted online.) To sign up for Endovasc shareholder alerts, please visit http://www.endovasc.com/html/e-list.html.