SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
Date of Report: August 17, 1999
MEDIMMUNE, INC.
(Exact name of registrant as specified in its charter)
Commission File Number: 0-19131
Delaware 52-1555759
(State of Incorporation) (I.R.S. Employer Identification No.)
35 West Watkins Mill Road, Gaithersburg, MD 20878
(Address of principal executive office (Zip Code)
Registrant's telephone number, including area code (301) 417-0770
No Exhibits are being filed with this report
CytoGam and RespiGam are registered trademarks of the Company and Synagis is a
trademark.
EDIMMUNE, INC.
MEDIMMUNE, INC.
Current Report on Form 8-K
ITEM 5. OTHER EVENTS
MedImmune, Inc. reported the information contained in the following press
release dated August 13, 1999:
FOR IMMEDIATE RELEASE
Contact:
William C. Roberts
Investor and Media Relations
MedImmune, Inc.
301-417-0770 x358
http://www.medimmune.com
<PAGE>
MEDIMMUNE ANNOUNCES NOVEL STRUCTURE OF URINARY
TRACT INFECTION VACCINE TARGET
-X-ray Structure of FimC-FimH Complex Published in Science-
Gaithersburg, MD, August 13, 1999 -- MedImmune, Inc. (Nasdaq: MEDI) today
announced that the x-ray structure of the FimC-FimH chaperone-adhesin complex of
uropathogenic E. coli has been published in the August 13, 1999 issue of
Science. The FimH adhesin, the tip protein at the end of bacterial pili which
facilitates attachment and subsequent colonization of E. coli to human bladder
tissue during infection, is required for colonization and antibody to FimH has
been shown to be protective against E. coli infection in a murine model. The
published structural data, obtained by Stefan D. Knight, Ph.D., associate
professor of molecular biology, and postdoctoral fellow Devapriya Choudhury,
Ph.D., both at Uppsala Biomedical Center in Sweden, allows scientists to
correlate structural data with the Company's ongoing urinary tract infection
(UTI) vaccine work. MedImmune's research team, led by Solomon Langermann, Ph.D.,
is developing its candidate vaccine for human use in collaboration with the
laboratories of Scott Hultgren, Ph.D., at Washington University School of
Medicine in St. Louis and Staffan Normark, M.D., Ph.D., at the Karolinska
Institute in Stockholm, Sweden.
"This new structural data regarding the FimC-FimH chaperone-adhesin interaction
will obviously provide valuable insight into the urinary tract infection vaccine
program," commented Scott J. Hultgren, Ph.D., professor of molecular
microbiology at the Washington University School of Medicine in St. Louis.
"Additionally, and perhaps most interestingly, this data provides a new insight
into the paradigm of protein folding."
"These data may validate MedImmune's choice of using the entire FimC-FimH
complex as our E. coli UTI vaccine candidate, since the FimC molecule is
required to direct proper folding of and to stabilize the FimH adhesin
structure," added Sol Langermann, Ph.D., director of immunology and molecular
genetics at MedImmune.
The article in Science is titled, "X-ray Structure of the FimC-FimH
Chaperone-Adhesin Complex from Uropathogenic E. coli." The FimH adhesin has two
major regions: One interacts with the FimC chaperone, while the other interacts
with mannose, a sugar attached to receptors in the lining of the bladder. This
FimH-mannose interaction allows the bacterium to bind and colonize the
urogenital tract. Since this is the critical interaction during infection, a
vaccine targeting this domain may mediate protection against infection. Of
particular interest in this study was the FimH domain which allows FimH to
interact with its chaperone, FimC. This domain forms a barrel-shaped
immunoglobulin fold, a structure typically made up of seven strands. However,
the FimH immunoglobulin fold lacks one of the strands. This forms a gap in the
FimH molecule, which would render it unstable. Scientists discovered that the
FimC chaperone, which also forms an immunoglobulin fold, temporarily shares its
seventh strand with the FimH subunit without actually parting with the shared
strand in a process called "donor strand complementation". This complementation
forms the FimC-FimH complex which stabilizes and allows proper folding of FimH,
and explains the basis for chaperone function. The discovery of donor strand
complementation provides a twist to the dogma of protein folding. According to
the thermodynamic hypothesis of 1972 Nobel-prize winner Christian B. Anfinsen,
Ph.D., the three dimensional shapes of proteins are determined solely by the
positions of the amino acid building blocks. However, this new data points out
that the structure of FimH is somewhat determined by specific interaction with
its chaperone.
UTIs are a significant medical problem and one of the most common disorders
prompting medical attention in otherwise healthy women and children. It is
estimated that by age 30 roughly 50 percent of women have had at least one
infection and 2-10 percent are affected by recurrent infections. Females are
generally more prone to UTIs simply due to their anatomy. Recent studies have
shown that, on average, women who are 18-40 years old get 1-2 infections over a
two-year period. Older adults are also at risk with the incidence as high as 33
out of 100 people. Most infections can be treated with antibiotics, however
recurrence is common and emerging antibiotic resistant bacteria create an
additional threat.
MedImmune's scientific collaborators, studying the cause of UTI infections,
found that bacteria establish infection in humans by using hair-like appendages,
called pili, to attach to bladder cells. The FimH adhesin, the protein at the
tip of the pili, is the "anchor" responsible for attachment. MedImmune
scientists have shown that vaccinating mice with this protein can produce
antibodies that prevent establishment of a UTI in the animals when challenged
with disease-causing E. coli bacteria. Furthermore, the antibodies elicited by
the vaccine prevented the attachment to bladder cells of 94 percent of random E.
coli UTI isolates and 100 percent of isolates from women with recurrent E. coli
infections tested in in vitro studies.
In 1998, MedImmune completed a vaccination study with FimH in non-human
primates. These studies demonstrated a dramatic decrease in bladder colonization
by E. coli in vaccinated animals. The Company expects to complete pre-clinical
development and file an investigational new drug (IND) application with the FDA
to begin clinical trials with its FimC-FimH complex UTI vaccine candidate in the
fourth quarter of 1999.
MedImmune, located in Gaithersburg, Maryland, is a biotechnology company focused
on developing and marketing products that address medical needs in areas such as
infectious disease, transplantation medicine, autoimmune disorders and cancer.
MedImmune markets three products through its hospital-based sales force and has
five new product candidates in clinical trials.
This announcement may contain, in addition to historical information, certain
forward-looking statements that involve risks and uncertainties. Such statements
reflect management's current views and are based on certain assumptions. Actual
results could differ materially from those currently anticipated as a result of
a number of factors, including risks and uncertainties discussed in the
Company's filings with the U.S. Securities and Exchange Commission.
MEDIMMUNE, INC
(REGISTRANT)
BY (SIGNATURE) /s/ David M. Mott
(NAME AND TITLE) David M. Mott, Vice Chairman and
Chief Financial Officer
(DATE) August 17, 1999
