Biogen Outperformer - 500 Beiträge pro Seite

[spirou]

Hallo zusammen,
daß Biogen mein persöhnlicher Outperformer ist, wissen
schon ein paar und deshalb habe ich mir die Mühe gemacht
den aktuellen Jahresbericht zu posten. Also viel Spaß beim
studieren und vielleicht auch diskutieren, also Biogen kaufen
und freuen.

spirou



UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM 10-K
(Mark One)

[X] ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 1999

OR

[ ] TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934

Commission file number: 0-12042

BIOGEN, INC.
(Exact name of Registrant as specified in its charter)

Massachusetts 04-3002117
(State or other jurisdiction (I.R.S. Employer
of incorporation or organization) Identification No.)



14 Cambridge Center, Cambridge, Massachusetts 02142
(Address of principal executive offices) (zip code)

Registrant`s telephone number, including area code: [phone]

Securities registered pursuant to Section 12(b) of the Act: None

Securities registered pursuant to Section 12(g) of the Act: Common Stock, $.01
par value
(Title of class)

Indicate by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the
Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to
file such reports), and (2) has been subject to such filing requirements for the past 90 days.

Yes _X_ No ___

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will
not be contained, to the best of Registrant`s knowledge, in definitive proxy or information statements incorporated by reference
in Part III of this Form 10-K or any amendment to this Form 10-K. [ ]

Aggregate market value of Common Stock held by nonaffiliates of the Registrant at March 16, 2000 (excludes shares held by
directors):
$12,913,220,996. Exclusion of shares held by any person should not be construed to indicate that such person possesses the
power, direct or indirect, to direct or cause the direction of management or policies of the Registrant, or that such person is
controlled by or under common control with the Registrant. Common Stock outstanding at March 16, 2000: 150,926,556
shares.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the Registrant`s definitive Proxy Statement for its 2000 Annual Meeting of Stockholders are incorporated by
reference into Part III of this Report, and portions of the Registrant`s 1999 Annual Report to Shareholders are incorporated by
reference into Parts II and IV of this Report.

2


PART I

ITEM 1 - BUSINESS

OVERVIEW

Biogen, Inc. ("Biogen" or the "Company") is a biopharmaceutical company principally engaged in the business of developing,
manufacturing and marketing drugs for human health care. Biogen, which was founded in 1978 and recently added by Standard
& Poor`s to the benchmark S&P 500 Index, currently derives revenues from sales of its AVONEX(R) (Interferon beta-1a)
product for the treatment of relapsing forms of multiple sclerosis and from royalties on worldwide sales by the Company`s
licensees of a number of products covered under patents controlled by the Company. Such products include certain forms of
alpha interferon, hepatitis B vaccines and hepatitis B diagnostic test kits, among others. The Company`s revenues from sales of
AVONEX(R) in 1999 were approximately $620.6 million, making AVONEX(R) the worldwide market leader among multiple
sclerosis therapies. The Company`s royalty revenues in 1999 were approximately $173.8 million.

Biogen continues to have an active development program related to AVONEX(R), and is conducting several important clinical
trials of the product. In 1999, Biogen completed a clinical study of AVONEX(R) in patients who had experienced only one
confirmed demyelinating event (multiple sclerosis-type exacerbation). The study showed a highly statistically significant beneficial
effect of AVONEX(R) in delaying the development of clinically definite multiple sclerosis. The study was stopped early following
positive results. The Company intends to file an application for a broadened prescribing label for AVONEX(R) with regulatory
agencies worldwide.

Biogen also continues to devote significant resources to its ongoing research and development efforts. The Company focuses its
efforts on areas where it has particular scientific strengths such as: multiple sclerosis, inflammatory diseases, cardiovascular
diseases, developmental biology and gene therapy. In 1999, the Company completed a Phase 2b clinical study of its
AMEVIVE(TM) (Human LFA-3/IgG1 fusion protein) product, also known as LFA3TIP, in patients with moderate to severe
chronic plaque psoriasis. Based on the encouraging Phase 2b data, the Company began a Phase 3 clinical trial in North
America, and is moving forward with planning for a Phase 3 clinical trial in Europe. Biogen anticipates beginning Phase 2 clinical
trials of AMEVIVE(TM) in a second indication during 2000. The Company also recently announced that it had successfully
completed an early-stage Phase 2 study of an adenosine A(1) antagonist small molecule product being studied as a treatment for
congestive heart failure. Additional studies using the lead back-up molecule for this pathway are planned. A third Biogen product
candidate in clinical trials experienced a set back in 1999. In November 1999, the Company announced that it had halted all
ongoing clinical trials of ANTOVA(TM) (Humanized anti-CD40 ligand monoclonal antibody), also known as humanized 5c8,
until it has completed a review of issues relating to adverse incidents involving thrombo-embolic events. Work to identify the
reasons for the adverse events is ongoing.

Biogen also has many earlier-stage research programs. These include: a program directed toward developing a novel inhibitor of
a particular immune response pathway as a potential therapy for several autoimmune diseases; a program focused on finding oral
small molecule drug candidates to inhibit the migration of white blood cells into tissue as a potential treatment for multiple
sclerosis and

2
3

certain chronic inflammatory diseases; a program in which the Company is exploring ways to treat certain central nervous system
disorders through use of proteins involved in inducing the formation and regeneration of tissue; and a program directed at
developing products based on human gene therapy technology. The Company is also exploring the use of functional genomics
technology to find novel therapeutics.

AVONEX(R) (INTERFERON BETA-1A)

Biogen currently markets and sells AVONEX(R) (Interferon beta-1a) for the treatment of relapsing forms of multiple sclerosis.
Multiple sclerosis is a progressive neurological disease in which the body loses the ability to transmit messages among nerve
cells, leading to a loss of muscle control, paralysis and, in some cases, death. Patients with active relapsing multiple sclerosis
experience an uneven pattern of disease progression characterized by periods of stability interrupted by flareups of the disease
after which the patient returns to a new baseline of functioning. AVONEX(R) is a recombinant form of a protein produced by
fibroblast cells in response to viral infection. AVONEX(R) has been shown in a pivotal clinical trial both to slow the
accumulation of disability and to reduce the frequency of exacerbations in patients with relapsing forms of multiple sclerosis.

Biogen began selling AVONEX(R) in the United States in 1996, and in the European Union ("EU") in 1997. AVONEX(R) is
on the market in over 50 countries, including Argentina, Australia, Brazil, Canada, Chile, Columbia, Cyprus, the Czech
Republic, the countries of the EU, Hungary, Israel, Mexico, Norway, Slovakia, South Africa, Switzerland, Turkey and the
United States.

In the United States, Canada and most of the major countries of the EU, Biogen uses its own sales force to market
AVONEX(R). In those countries, Biogen distributes AVONEX(R) principally through wholesale distributors of pharmaceutical
products, mail order, specialty distributors or shipping service providers. In other countries, Biogen sells AVONEX(R) to
distribution partners who are then responsible for most marketing and distribution activities. The Company has entered into
distribution agreements covering Australia, Eastern Europe, Greece, Israel, Italy, Japan, Latin America, the Middle East, New
Zealand, Portugal, South Africa, Spain and Turkey. Under most of these agreements, the distribution partners are responsible
for marketing and distributing AVONEX(R).

Biogen is currently conducting several clinical studies of AVONEX(R). These include: a dose comparison study, initiated in
1996, comparing the approved dosage of AVONEX(R) with a higher dose; an open-label follow-up study initiated in 1995 to
obtain long-term safety and antigenicity data; a clinical study of AVONEX(R) in patients with secondary progressive multiple
sclerosis, initiated in 1998; and a Phase 2 clinical study of AVONEX(R) in the treatment of idiopathic pulmonary fibrosis which
also commenced in 1998.

Biogen also recently completed a clinical study of AVONEX(R) in patients who had experienced only one confirmed
demyelinating event (multiple sclerosis-type exacerbation). The study, which was initiated in 1996, showed a highly statistically
significant beneficial effect of AVONEX(R) in delaying the development of clinically definite multiple sclerosis. Clinically definite
multiple sclerosis is identified by the presence of at least two demyelinating events, separated by time and location in the central
nervous system. The study was stopped early following positive results. The Company intends to file an application for a
broadened prescribing label for AVONEX(R) with regulatory agencies worldwide.

3
4

Biogen is also exploring new ways to improve the formulation and delivery of AVONEX(R). In February 1999, Biogen entered
into a collaborative agreement with Inhale Therapeutic Systems, Inc. under which the parties are working towards development
of a dry powder formulation of AVONEX(R) for pulmonary delivery using Inhale`s deep-lung delivery system. Biogen is also
continuing to work towards development of a pre-filled syringe formulation of AVONEX(R).

Revenues from sales of AVONEX(R) in 1999 were $620.6 million or approximately 78% of total revenues. Revenues from
sales of AVONEX(R) in 1998 and 1997 were $394.9 million and $240.0 million, respectively, or approximately 71% and 58%
of total revenues, respectively. Approximately 71% of AVONEX(R) sales in 1999, 77% of AVONEX(R) sales in 1998, and
92% of AVONEX(R) sales in 1997, were generated in the United States. Sales to three major wholesale distributors and a
specialty distributor in the United States accounted for 13%, 11%, 11% and 15%, respectively, of total revenues in 1999.

MAJOR RESEARCH AND DEVELOPMENT PROGRAMS

Biogen`s research is focused on biological systems and processes where its scientific expertise in molecular biology, cell biology,
immunology and protein chemistry can lead to a greater understanding of disease processes and, as a result, to the creation of
new pharmaceuticals. Biogen selects product candidates from its research programs to test in clinical trials, focusing its efforts on
those agents which it believes have the greatest potential competitive advantages and large commercial markets. Described
below are Biogen`s major research programs.

AMEVIVE(TM) (LFA3TIP)

Inflammation is the result of the body`s immune response to infection and injury. In many autoimmune diseases, the inflammation
process is directed inappropriately against the body`s own tissues, causing temporary or permanent damage. Biogen has focused
the efforts of its inflammation programs on developing drugs to inhibit specific cellular interactions critical to the inflammation
process. Central to inflammation is the activation of T-cells, specialized white blood cells which initiate and control the immune
response. One of the cellular pathways which is important for the activation of T-cells is the LFA-3/CD2 pathway.
AMEVIVE(TM) (LFA3TIP) is a recombinantly engineered protein designed to modulate immune responses by binding to the
CD2 receptor. Biogen is developing AMEVIVE(TM) as a treatment for certain autoimmune diseases. In 1999, the Company
completed a Phase 2b clinical study of AMEVIVE(TM) in patients with moderate to severe chronic plaque psoriasis. Based on
positive data from the Phase 2b study, the Company began a Phase 3 study in North America and is moving forward with
planning for a Phase 3 study in Europe. Psoriasis is a chronic autoimmune disease that is characterized by inflammation and
thickening of the skin. An estimated 500,000 psoriasis patients in the United States have a severe enough form of the disease to
need systemic therapies. Biogen anticipates beginning Phase 2 clinical trials of AMEVIVE(TM) in a second indication during
2000.

ADENOSINE A(1) ANTAGONISTS

In March 1997, Biogen entered into a research collaboration and license agreement with CV Therapeutics, Inc. ("CVT")
pursuant to which the Company obtained rights under CVT`s patents and know-how to develop and market molecules that act
as highly selective antagonists of the adenosine A(1)

4
5

receptor. The adenosine A(1) receptor is expressed principally in the heart, brain and kidney, and in the kidney mediates
vasoconstriction, renal function and reabsorption of fluids. Biogen is developing small molecule adenosine A(1) antagonists as a
treatment for congestive heart failure. Congestive heart failure is a chronic progressive disease that affects four to five million
people in the United States. Patients with the disease experience both a chronic course as well as acute episodes of heart failure
that usually require hospitalization. Reduction in kidney function and the formation of edema, or fluid retention, in lungs and
extremities are significant symptoms of chronic heart failure, leading to increased morbidity, hospitalization and death. In 1999,
Biogen successfully completed an early-stage Phase 2 study comparing CVT-124, a particular small molecule product, with
existing therapies in the acute treatment of congestive heart failure. Additional studies using the lead back-up molecule for this
pathway are planned.

ANTOVA(TM) (HUMANIZED 5C8)

The human immune system generates two types of responses: humoral (also known as antibody) responses and cell-mediated
responses. When CD40 ligand ("CD40L") on the surface of an activated T-cell binds to CD40 on the surface of a B-cell, the
production of antibodies is triggered. When CD40L on the surface of an activated T-cell binds to CD40 on the surface of a
variety of other cells, such as macrophages and dendritic cells, the cells become activated, triggering an inflammatory response.
The inhibition of the CD40-CD40L pathway offers a unique target for modulating both types of immune responses.

Biogen is developing ANTOVA(TM), a humanized monoclonal antibody that binds to CD40L, as a treatment for a variety of
autoimmune diseases and as a therapy for preventing organ and cellular transplant rejection. During 1999, the Company was
involved in an ongoing Phase 2 safety study of ANTOVA(TM) in patients with immune thrombocytopenic purpura, as well as
Phase 2 studies of ANTOVA(TM) in lupus nephritis, renal transplantation, pancreatic islet cell transplantation, Factor VIII
inhibitor syndrome and multiple sclerosis. In November 1999, the Company announced that it had halted all existing clinical trials
of ANTOVA(TM) until it has completed a review of issues relating to adverse incidents involving thrombo-embolic events.
Work to identify the reasons for the adverse events is ongoing.

LT-BETA RECEPTOR

The lymphotoxin-beta receptor ("LT-Beta Receptor") pathway is involved in controlling the maintenance of proper immune
interactions and the correct positioning of key cell types in the immune system. Both elements are crucial for the immune system
to function properly. The LT-Beta Receptor pathway serves as a novel access point to modulate autoimmune disease. Biogen is
developing its LT-Beta Receptor as a potential treatment for certain autoimmune diseases and expects to start Phase 1 safety
studies in 2001.

VLA-4 INHIBITORS

VLA-4 (Very Late Antigen-4) is a receptor that appears on the surface of white blood cells and binds to VCAM-1, a protein
found on the surface of vascular endothelial cells, as well as extracellular matrix proteins, fibronectin and osteopontin. The
VLA-4 pathway facilitates migration of white blood cells into tissue as part of the body`s normal response during inflammation.
This inflammatory response

5
6

can be severely damaging or even life threatening when it is directed against the body`s own tissue in autoimmune diseases and
may cause serious collateral injury in chronic immune inflammatory diseases such as asthma. Biogen scientists have developed
VLA-4-specific small molecule inhibitors designed to interrupt the cell adhesion activity of VLA-4 as a means of blocking the
inflammation process in a highly specific manner.

In December 1997, Biogen entered into a collaborative research, development and license agreement with Merck & Co., Inc.
("Merck") under which Biogen and Merck are collaborating on developing small molecule inhibitors of VLA-4. Under the
agreement with Merck, Biogen has rights to develop, market and sell small molecule inhibitors of VLA-4 for the treatment of
multiple sclerosis, kidney diseases and disorders, inflammatory bowel disease and most diseases with small patient populations.
Merck has rights to develop, market and sell small molecule inhibitors of VLA-4 in all other indications, including asthma. Early
in 1999, Merck completed a Phase 2a study in asthmatic patients using an aerosolized small molecule inhibitor of VLA-4,
known as BIO-1211. Merck subsequently determined that the results of the trial did not support continued development of that
particular compound. Collaborative efforts to identify a suitable oral small molecule inhibitor drug candidate continue at Merck
and Biogen.

HEDGEHOG PROTEINS

Hedgehog proteins are a class of novel human proteins that are responsible for inducing the formation or regeneration of tissue.
In 1996, the Company entered into a research collaboration and license agreement with Ontogeny, Inc. ("Ontogeny") for the
development of three specific "hedgehog" proteins. Under its agreement with Ontogeny, Biogen has access to exclusive
worldwide rights to develop therapeutics directly based on Ontogeny`s proprietary family of sonic, indian and desert hedgehogs
for most disease indications. In 1998, Biogen and Ontogeny extended the hedgehog research program and broadened the
collaboration to include gene therapy. The Company`s current focus is the study of the hedgehog proteins for the treatment of
certain central nervous system disorders.

GENE THERAPY

In 1995, the Company entered into a collaborative research agreement with Genovo, Inc. ("Genovo") for the development of
certain human gene therapy treatments. Under this agreement, Biogen received rights related to certain diseases of the liver and
lung. Genovo has also granted to Biogen rights under Genovo`s gene therapy technology for development of certain gene
therapy products in connection with the treatment of cancer.

OTHER RESEARCH PROGRAMS

As part of its further research efforts, Biogen is exploring the use of growth factors to prevent or treat the degeneration of organs
following damage. The Company is also investigating new ways to modify immune responses more specifically in order to treat
diseases of the immune system. In addition, through its collaborations with CuraGen Corporation, Incyte Pharmaceuticals, Inc.
and Genetica Incorporated, Biogen is exploring the use of functional genomics technology to find novel therapeutics.

6
7

RESEARCH AND DEVELOPMENT COSTS

For the years ended December 31, 1999, 1998 and 1997, Biogen`s research and development costs were approximately
$221.2 million, $177.2 million and $145.5 million, respectively.

RISKS ASSOCIATED WITH DRUG DEVELOPMENT AND COMMERCIALIZATION

Certain of the statements set forth above regarding the Company`s research and development programs, such as statements
regarding the anticipated commencement of clinical trials of drugs in development, are forward-looking, and are based upon the
Company`s current belief as to the outcome and timing of such future events. These events are subject to a number of factors
and uncertainties which could cause actual results to differ materially from those described in the forward-looking statements.
Many important factors affect the Company`s ability to successfully develop and commercialize drugs, including the need to
demonstrate the safety and efficacy of drug candidates at each stage of the clinical trial process, to overcome technical hurdles
that may arise, to meet applicable regulatory standards, to receive required regulatory approvals, to be capable of producing
drug candidates in commercial quantities at reasonable costs, to obtain and maintain all necessary patents or licenses, to
compete successfully against other products, and to market products successfully. There can be no assurance that any of the
products described in this section or resulting from Biogen`s research and development programs will be successfully developed,
prove to be safe and efficacious at each stage of clinical trials, meet applicable regulatory standards, be capable of being
produced in commercial quantities at reasonable costs, be successfully marketed or successfully meet challenges from
competitive products.

For a detailed discussion of the risks associated with the Company`s drug development and commercialization program, see the
Company`s 1999 Annual Report to Shareholders --- "Management`s Discussion and Analysis of Financial Condition and Results
of Operations --- Outlook," which is incorporated herein by reference under Item 7 hereof.

PRINCIPAL PRODUCTS BEING MARKETED OR DEVELOPED BY BIOGEN`S LICENSEES

ALPHA INTERFERON

Alpha interferon is a naturally occurring protein produced by normal white blood cells. Biogen has been granted patents covering
the production of alpha interferon through recombinant DNA techniques. See "Patents and Other Proprietary Rights." Biogen`s
worldwide licensee for recombinant alpha interferon, Schering-Plough Corporation ("Schering-Plough"), first began commercial
sales of its Intron(R) A brand of alpha interferon in the United States in 1986 for hairy-cell leukemia. Schering-Plough now sells
Intron(R) A worldwide for as many as 16 indications. The United States Food and Drug Administration (the "FDA") has
approved Intron(R) A for the treatment of chronic hepatitis B and hepatitis C, hairy-cell leukemia, AIDS-related Kaposi`s
sarcoma, condylomata acuminata, for injection as an adjuvant treatment to surgery in patients at high risk for systemic recurrence
of malignant melanoma, and for use in conjunction with anthracycline-containing combination chemotherapy for the initial
treatment of patients with clinically aggressive non-Hodgkin`s lymphoma.

In late 1998, Biogen filed for arbitration against Schering-Plough in a dispute over the amount of royalties payable to Biogen on
sales of REBETRON(R), a combination product containing the Intron(R) A injection product and REBETOL(R) (ribavirin,
USP capsules). Schering-Plough sells REBETRON(R) in the United States as a treatment for

7
8

chronic hepatitis C. A hearing in connection with the arbitration was conducted in January 2000. In March 2000, the arbitration
panel found in favor of Schering-Plough, and rejected Biogen`s claim that royalty payments should be based on the higher rate
for combination products called for under the 1979 agreement between the parties, and not on the Intron(R) A component
alone. Biogen does not expect to suffer any financial impact as a result of the arbitration panel`s decision since Schering-Plough
is presently paying royalties only on the Intron(R) A component, and the decision will have no effect on those royalties.

Royalties from Schering-Plough on sales of Intron(R)A accounted for approximately 13%, 16% and 19% of Biogen`s revenues
in 1999, 1998 and 1997, respectively.

For a discussion of the length of Schering-Plough`s royalty obligation to Biogen on sales of alpha interferon products, see
"Patents and Other Proprietary Rights - Recombinant Alpha Interferon."

HEPATITIS B VACCINES AND DIAGNOSTICS

Hepatitis B is a blood-borne disease which causes a serious infection of the liver and substantially increases the risk of liver
cancer. More than 250 million people worldwide have chronic hepatitis B virus infections. Biogen holds several important
patents related to hepatitis B antigens produced by genetic engineering techniques. See "Patents and Other Proprietary Rights -
Recombinant Hepatitis B Antigens." These antigens are used in recombinant hepatitis B vaccines and in diagnostic test kits used
to detect hepatitis B infection.

Hepatitis B Vaccines

Approximately 100 countries around the world, including the United States, have added the vaccination against hepatitis B to
their routine immunization programs for all children. The United States Centers for Disease Control and the American Academy
of Pediatrics have also recommended universal immunization of ten-year-old children and at-risk adolescents. The United States
Occupational Safety and Health Administration has recommended that all persons with an occupational exposure to blood and
other infectious material receive the hepatitis B vaccine.

SmithKline Beecham Biologicals s.a. ("SmithKline") and Merck are the two major worldwide marketers of hepatitis B vaccines.
Biogen has licensed to SmithKline exclusive rights under Biogen`s hepatitis B patents to market hepatitis B vaccines in the major
countries of the world, excluding Japan. SmithKline currently pays Biogen royalties based on sales of SmithKline`s vaccine in the
United States and in over 15 other countries. In 1990, SmithKline and Biogen entered into a sublicense arrangement with Merck
under which Biogen currently receives royalties. Biogen has also licensed rights relating to hepatitis B vaccines under its hepatitis
B patents to Merck and The Green Cross Corporation on a non-exclusive basis in Japan. Royalties from SmithKline and Merck
together accounted for approximately 6%, 9% and 14% of Biogen`s revenues in 1999, 1998 and 1997, respectively.

Hepatitis B Diagnostics

Biogen has licensed its proprietary hepatitis B rights, on an antigen-by-antigen and nonexclusive basis, to diagnostic kit
manufacturers. Biogen currently has hepatitis B license or license and supply agreements for diagnostic use with more than 15
companies, including Abbott Laboratories, the major worldwide marketer of hepatitis B diagnostic kits, Ortho-Clinical
Diagnostics, Organon Teknika B.V. and Roche Diagnostic Systems, Inc.

8
9

For a discussion of the length of the royalty obligation of SmithKline and Merck on sales of hepatitis B vaccines and the
obligation of Biogen`s other licensees on sales of hepatitis B-related diagnostic products, see "Patents and Other Proprietary
Rights - Recombinant H

[spirou]

Nachdem der Jahresbericht doch etwas länger ist, gibt es halt die
Adresse für euch:

http://www.nasdaq.com/asp/quotes_news.asp?symbol=BGEN%60&sel…

schönen Tag noch


spirou