DIREVO announces validation of bestMab(TM)

Powerful new approach for the optimization of therapeutic antibodies
generates optiMIRA(TM), an enhanced version of Adalimumab (Humira®)

Cologne (Germany), May 6, 2008 - DIREVO Biotech AG announced today
that it has validated its "bestMab(TM)" platform through the
generation of an optimized version of the anti-inflammatory antibody,
Adalimumab (Humira®), with unprecedentedly strong binding properties.
optiMIRA(TM) shows 300-times tighter antigen binding than Humira®,
and more than 15-fold tighter binding than the previously most
advanced optimized Humira® derivative, which was generated using
display technology. The results of this study were presented on May
1st, 2008 at the Fourth Annual Protein Engineering Summit (PEGS)
conference in Boston, USA. The presentation can be viewed at
http://www.direvo.com/bestMab/PEGS

The bestMab(TM) technology comprises a novel, integrated, and highly
effective platform for improving the properties of therapeutic
antibodies. The platform achieves this without making use of display
technologies, and is applicable to all types of antibodies from any
origin, including antibodies derived from either immunized mice or
recombinant antibody libraries. Significantly, the bestMab(TM)
process identifies virtually all mutations that can improve the
antibody of interest. Using bestMab(TM), DIREVO optimized the
marketed antibody, Humira®, to generate optiMIRA(TM), which binds to
TNFa with an exceptional binding strength (femtomolar affinity).

"This is a major technical and commercial breakthrough in antibody
engineering that has the potential to significantly enhance antibody
drug development," said Dr. Thomas von Rüden, CEO of DIREVO. "I am
very proud of our interdisciplinary team of scientists and
technicians who have made this important contribution to a key area
of antibody R&D."

DIREVO will use bestMab(TM) as a proprietary cornerstone of its
therapeutic antibody platform. Based on bestMab(TM), DIREVO will
generate superior 2nd generation antibodies and improve success rates
of antibodies in development, both for internal proprietary programs
and through partnerships with the pharmaceutical and
biopharmaceutical industries.

- end -

More about bestMab(TM)
The bestMab(TM) technology relies on DIREVO's leading protein
engineering platform, which is characterized by highly predictive
screens of high throughput. These screens allow effective antibody
engineering using the more informative "clonal" and "solution-based"
assays, as opposed to the more traditional use of display technology.
Another distinctive feature of the bestMab(TM) approach is its more
comprehensive and efficient approach to the engineering of antibody
properties. This respectively translates into the more complete
generation of IP covering all changes that can improve a given
antibody, as well as into antibodies that reach product qualification
goals with fewer mutations.

Using the bestMab(TM) approach, highly valuable synergistic
interactions can be identified by the extensive generation and
testing of a large number of combinatorial antibody libraries. In
each library, two antibody binding region (complementarity
determining region, or CDR) positions are paired for simultaneous
co-optimization. This approach is then extended to every residue in
all six CDRs, to yield a large number of such "paired-saturation"
libraries. Extensive exploitation of such an approach is only
possible using screens of very high throughput. For example, in the
first screening round, well over 100,000 variants were individually
and quantitatively screened to compare their properties on a
proprietary platform that allows over 50,000 variants to be screened
per day.

Elements of the bestMab(TM) approach thus ensure that:
(i)     virtually every amino acid substitution that can improve a
given antibody is identified,
(ii)    synergistic interactions that are typically missed in other
approaches are identified,
(iii)   the number of mutations is minimized because the antibody
receives the optimal combination of amino acid
        exchanges,
(iv)   so called "neutral mutations" that do not contribute to
improvement are excluded and
(v)    the entire process is rapid and reliable.

A further important attribute of this DIREVO screening platform is
its facility in the simultaneous optimization of multiple parameters.
These include, in addition to increasing affinity, engineering
binding specificity and improving the antibody's inherent
expressibility, stability, pH binding profile, and other important
antibody characteristics.

The DIREVO bestMab(TM) optimization program for Humira® yielded a
complete series of variants with successively improved affinities.
The best variant created by the bestMab(TM) process, optiMIRA(TM),
shows 300-times tighter antigen binding than Humira®. It also binds
TNFa more than 15-fold tighter than cb1-3, the previously most
advanced optimized Humira® derivative, which was generated using
display technology (Rajpal et al. (2005) PNAS; 102:8466-8471). The
series of improved antibodies generated by bestMab(TM) also included
a variant with binding strength equal to cb1-3, but with 40% fewer
mutations. The increased binding strength demonstrated in these
optimized antibodies also translated into biological potency as
determined in experiments measuring protection against TNFa-induced
cell killing.

DIREVO Biotech AG
DIREVO Biotech AG generates superior bioengineered products and
processes for industrial and pharmaceutical markets by enhancing
nature's potential. The Company's portfolio includes optimized
proteins, optimized bioprocesses and other bio-molecules, in
research, in commercial development and on the market. DIREVO
develops products both independently and with global leaders such as
Danisco/Genencor, Nestlé, AstraZeneca/MedImmune and Pfizer. DIREVO
Biotech is committed to a tailored approach to addressing customer
needs and market opportunities.

DIREVO's biopharmaceutical business generates improved second
generation therapeutics and discovers and optimizes novel
first-generation therapeutics. DIREVO offers early stage partnering
from internal therapeutic antibody and protease discovery programs as
well as collaborations on the optimization of a wide range of
therapeutic proteins.

DIREVO Biotech AG is privately held and located in Cologne, Germany.
Additional information is available at: www.direvo.com

Contact:
DIREVO Biotech AG
Dr. Thomas von Rüden
CEO
Telephone: + 49 221 8887-121
E-mail: info@DIREVO.com