Biovail Corporation

Biovail Corporation

Biovail Corporation International has developed a second
generation controlled released once-daily Diltiazem
formulation (Diltiazem OD ER Tiazac) for the management
of hypertension and angina. It incorporates an advanced
drug delivery technology which addresses the major
limitations of currently marketed first generation once-daily
diltiazem products.

Diltiazem has grown to be one of the leading compounds in
the world since its introduction in 1982. Worldwide sales in
1996 were in excess of $1.7 billion (US).

The calcium channel blocker market has grown to reach
annual sales of $3.5 billion in the United States in 1996
through the introduction of a number of highly effective
anti-hypertensives, and through the successful re-design of
their delivery systems. The introduction of verapamil,
nifedipine and diltiazem in the early 1980`s provided several
highly effective and well tolerated products for the
management of hypertension. Since them, they have all
been re-engineered to incorporate various types of drug
delivery systems which have greatly enhanced their
therapeutic characteristics and marketability. The dominant
products today are once-daily nifedipine, diltiazem and
verapamil. The growth of these compounds can be
expected to continue into the future as their effectiveness
and safety are further enhanced through the use of
increasingly sophisticated and reliable drug delivery
technologies.

Tiazac`s unique profile makes it an ideal compound for the
treatment of both hypertension and angina. Tiazac
incorporates an advanced drug delivery technology which
addresses the major limitations of currently marketed
diltiazem products.

There is a growing awareness and acceptance by physicians
of once-daily diltiazem compounds as safe and effective,
first-line treatment for mild to moderate hypertension. Also,
more and more, prescribers are switching angina patients
from immediate-release diltiazem products to once-daily
products.

Although there are a number of once-daily diltiazem
products, many of the currently marketed products are
available in a limited number of strengths, and not all once-
daily diltiazem products are approved for both hypertension
and angina. Tiazac has a number of key competitive
advantages over existing once-daily diltiazem products on
the market.

Tiazac Key Advantages

- Tiazac will be approved for the treatment of both
hypertension and angina, whereas many competing once-
daily diltiazem products are only approved for the
treatment of angina.
- The widest dosage range for greater dose flexibility and
titration, which prescribers consider key, especially in the
treatment of hypertension.
- An incidence of side-effects comparable to placebo at all
dosing levels.
- A more compact capsule size which is on average 40%
smaller than equivalent does of competing products.
Tiazac is the only once-daily product that allows the use
of a single capsule for doses ranging from 120mg to
360mg, thus providing enhanced convenience, improved
compliance, and optimal dosing flexibility.
- Tiazac`s unique pharmacokinetic profile is associated with
higher diltiazem blood levels during the day, when blood
pressure is at its highest.
- Both in the treatment of angina and hypertension, Tiazac`s
clinical efficacy is maintained for 24 hours.
- Tiazac can be taken with or without food
- The patented technology and unique formulation provide
an effective barrier to generic duplication.
- Diltiazem`s proven history of safety and efficacy.

In summary, Tiazac`s unique profile allows prescribers to
target both hypertensive and angina patients, and also
patients whose profile previously led physicians to prescribe
other calcium channel blockers. The market share of once-
aily diltiazem products approved for both hypertension and
angina is expected to continue to grow substantially.
Tiazac`s key competitive advantages position it to gain
rapid penetration of both the anti-hypertensive and the
anginal market.

Diltiazem SR OD ER (Tiazac) received FDA approval in
1995. Tiazac is marketed in the United States by Forest
Laboratories, Inc. In Canada, Tiazac is marketed by Crystal
Corporation, an operating division of Biovail Corporation
International. Biovail Diltiazem OD ER received approval
in the United Kingdom in April 1996. Additional European
approvals are expected shortly. Biovail`s Diltiazem OD ER
is licensed to DuPont Merck for the United Kingdom and
Ireland, to Pierre Fabre S.A. for France, to Alter for Spain,
to Zambon B.V. for the Netherlands, and to Ratiopharm
and Heumann Pharma for Germany. Other international
licensing agreements will be announced shortly.

CORPORATE PROFILE

Biovail Corporation International, headquarted in Toronto,
Canada, is an international full-service pharmaceutical
company, engaged in the formulation, clinical testing,
registration and manufacture of drug products utilizing
advanced drug delivery technologies.

The Company`s strategy is to control all facets of its
research and development efforts, including formulation
development, clinical studies, regulatory submissions and
manufacturing. This integrated approach enables the
Company to enter into licensing agreements with major
pharmaceutical partners seeking drug delivery expertise,
coupled with operational synergies, flexibility and cost
efficiencies.

Biovail applies its oral drug delivery technologies to drug
compounds free of patent protection, in order to develop
novel formulations which improve on conventional dosage
forms, or to produce generic versions of branded
controlled-release products to provide a price advantage.
The Company focuses on the development of products for
the treatment of chronic diseases, including cardiovascular
diseases, arthritis, bronchial conditions and pain
management.

HIGHLIGHTS

- Growing Market for Oral Controlled-release Products.
The oral controlled-release pharmaceutical market is
currently growing in excess of 30% annually, offering
significant opportunities for Biovail and its licensing
partners. Of more than 40 products using controlled-release
technology, 20 products are currently devoid of patent
protection. U.S. sales of controlled-release products
exceeds $6 billion. In addition, Biovail is one of a limited
number of companies with a successful track record of
developing and gaining approval for oral controlled-release
pharmaceutical products.

- Flexible Proprietary Technology. The Biovail controlled-
release technologies allow pharmaceutical compounds to be
administered once-daily, releasing them in predetermined
and controlled fashion over a 24 hour period. The result
typically is enhanced therapeutic effectiveness, reduced side
effects and improved patient compliance. Biovail has 5
different technology platforms. These proven technologies
are highly flexible, providing a broad range of release
profiles that can be tailored to the physical, chemical and
clinical properties of a given drug compound.

- Numerous Products Successfully Developed. Biovail has
successfully developed and licensed 12 products which are
currently marketed by major pharmaceutical companies
worldwide. Important products include Tiazac (Diltiazem
OD ER), licensed both in the U.S. and a growing number of
European countries, once-daily formulations of ketoprofen,
marketed under the brand name Oruvail by Wyeth-Ayerst
Laboratories in the U.S. and under several brand names by
Phone-Poulenc Rorer internationally, Theo-24
(thaophylline) marketed by UCB, and Norpace CR
(disopryamide) by G.D. Searle.

- Promising Product Pipeline. Biovail has a strong product
pipeline with numerous products under development:
including both NDA (branded) and ANDA (generic)
controlled-release products.

RECENT EVENTS

- In 1995 Biovail received approval from the U.S. Food and
Drug Administration to market Tiazac in the United States.
This once-daily extended release formulation of Diltiazem is
used in the treatment of both hypertension and angina, and
competes in the $3.2 billion U.S. calcium channel blocker
market; it has the potential to be a $100-200 million
branded product. Biovail`s Diltiazem OD ER was approved
in the United Kingdom in April 1996. Additional European
approvals, and HPB approval in Canada is expected shortly.

- To support the product development effort, Biovail has
recently established a new 24,000 square foot R&D facility
in West Toronto, Ontario. The West Toronto center
supports the Company`s expanded R&D activities, which
has produced a substantial product pipeline. The R&D
group works closely with the new R&D Division in Puerto
Rico.

- To support Biovail`s marketing efforts in Canada, the
company established Crystaal Corporation, an operating
division of BCI, headquartered in Montreal, Quebec.
Crystaal Corporation is dedicated to providing high quality,
cost effective pharmaceuticals to Canadian health care
professionals, patients and third party payers. Crystaal
Corporation`s portfolio includes products manufactured
and/or licensed by Biovail, as well as products in-licensed
from external sources. Crystaal`s strategy is to source and
develop worldwide in-licensing agreements for original
and/or multisource products, and to form strategic joint
ventures and partnerships providing access to novel
pharmaceutical compounds.

- In 1995 Biovail acquired the know-how and the R&D and
manufacturing resources of Puerto Rico based Galephar
P.R., Inc., a drug delivery company specializing in the
development of controlled-release products Galephar was
the co-developer of Biovail`s Tiazac, its once-daily
Diltiazem product.

- In 1995 Biovail received approval by the FDA for Oruvail
100mg and 150mg extended release capsules. Market
clearance for these two dosing strengths greatly increases
the dosing flexibility of Oruvail 200mg extended release
capsules. The addition of these two new longer dosages
permits the use of Oruvail in elderly and renally impaired
patients, a population segment where the product was
previously contraindicated. Oruvail was approved in
September 1993, and launched by the Company`s marketing
partner Wyech-Ayerst Laboratories in October, 1993.
Oruvail is used to treat osteoarthritis and rheumatoid
arthritis, conditions affecting a total of 18 million
Americans. The market for these indications exceeds $2
billion and provides Oruvail with an estimated market
potential of U.S. $200-300 million. 1995 sales were U.S.
$150 million.

- Recent Licensing Agreements. Biovail has recently
entered into a number of licensing agreements. Diltiazem
OD ER (Tiazac) received FDA approval in 1995. Tiazac is
marketed in the United States by Forest Laboratories, Inc.
Biovail`s Diltiazem OD ER received approval in the United
Kingdom in April 1996. Additional European approvals are
expected shortly. Biovail`s Diltiazem OD ER is licensed to
DuPont Merck for the United Kingdom and Ireland, to
Pierre Fabre S.A. for France, to Alter for Spain, to Zambon
B.V. for the Netherlands, and to Ratiopharm and Heumann
Pharma for Germany.

Company Details

Year Established: 1982

Company Information

John Miszuk
Title: VP, Controller & Asst Secretary
Telephone: (905) 286-3020
Fax: (905) 286-3021

Products

Diltiazem Od

Oruvail - Ketoprofen Sr Od
used for arthritis, non-steroidal anti-inflammatory

Norpace - Disopyramide Sr Bid
used for arrhythmias, type 2 antiarrhythmic

Theo-24 - Theophylline Sr Od
used for asthma and bronchitis, xanthine bronchodilator

Isoket Retard - Isosorbide Dinitrate Sr Od
used for angina, vasodilator

Elanten Long - Isosorbide-5-mononitrate Sr Od
used for angina, vasodilator

Sirdalud Cr - Tizanidine Sr Od
used for muscle relaxant

Gastro-timelets Gastromax - Metoclopramide Sr Od
used for gastric reflus, GI tract mobility modifier

Novagent - Ibuprofen Sr Od
used for arthritis, non-steroidal anti-inflammatory

Beta-timelets - Propranolol Sr Od
used for hypertension and angina, beta blocking agent

Tiamon Mono - Dihydrocodeine Sr Od
used for analgesic, opioid derivative

Regenon Retard, Diethylpropion Sr Od
used for anti-obesity therapy, symaphomimetic agent

Nifedipine Xl
used for angina and hypertension, calcium channel blocker

Verapamil Sr Od Capsules
used for hypertension and arrhythmias, calcium channel blocker

Diltiazem Cd
used for angina and hypertension, once-daily calcium channel blocker

Dilitiazem Sr Bid
used for angina and hypertension, twice-daily calcium channel blocker

Pentoxifylline Sr
used for peripheral chronic, occlusive arterial disease

Pain Management

Synthetic Retinoids

Antilipemic Agents

Calcium Antagonists

Services

Biotechnology