London, 18 March 2002
DyoDelta Biosciences Ltd announced today that it
entered into a collaboration for the exclusive license of a novel
proprietary pharmaceutical compound programme developed by Professor John
Matsoukas, Head of Medicinal Chemistry at the University of Patras in
Greece. The lead compound
DDB-202, is at the forefront of modern approaches towards the therapeutic
management of Multiple Sclerosis (MS) that involve the design and use of
peptide analogues of disease-associated myelin epitopes to induce
peripheral T cell tolerance. MBP
(Myelin Basic Protein) is one of the candidate autoantigens in MS and
DDB-202 is designed as an analogue of MBP’s most immunodominant region
in human MS, therefore conferring an expected immunomodulatory activity
and is hoped to be used to prevent and treat this debilitating disease.
The use of peptides as therapeutic entities has been
attempted unsuccessfully so far due to their sensitivity to proteolytic
enzymes. DDB-202 is a stable
MBP epitope peptide molecule with the same biological activity as other
unstable molecules. In
addition to efficacy shown in experimental allergic encephalomyelitis (EAE)
models of multiple sclerosis, there is evidence that DDB-202 induces the
production of IL-10 by T-cells from MS patients.
Dimitri F. Dimitriou, CEO of DyoDelta Biosciences
commented: “We are delighted to gain access to a compound with such
qualities that could become a useful treatment for MS.
We know a few other companies have used similar MBP approaches but
to our knowledge, DDB-202 seems to have solved many the issues with this
chemistry, including the stability problems that others have faced.”
Prof Matsoukas said: "I am very excited to see
that years of research at my labs are coming to fruition.
Following the remarkable stability and efficacy of DDB-202 in
animal models and in vitro with human T cells, this forms the basis for
DDB-202 to proceed to clinical trials in the near future."
DyoDelta Biosciences is seeking development partners
for DDB-202.
DyoDelta Biosciences Ltd is London-based company,
focusing on exploiting opportunities in the Life Sciences.
Providing broad "bio-incubator" services,
DyoDelta Biosciences creates value by progressing the development of novel
compounds and research know-how through collaborations.
The developments in the pharmaceutical industry over the past
years, have resulted in a number of niche companies specialising in
different parts of drug development and commercialisation, effectively
covering all industry components. DyoDelta
Biosciences facilitates the progression of assets through partnering, all
the way to the stage whereby they can eventually be marketed by major
pharmaceutical companies on a global basis.
DyoDelta Biosciences also guides and supports pharma
and biotech companies in creating partnerships with others, in an
integrated way, including: identification of potential partners,
initiation of contacts, commercial and technical evaluation of
opportunities, M&A activities, negotiations of terms, contract reviews
and preparation (with DyoDelta's legal contacts) and issues arising out of
existing collaborations.
Contact for further information
Dimitri F. Dimitriou
Chief Executive Officer
DyoDelta Biosciences Ltd
Berkeley Square House
Berkeley Square
London W1J 6BD
UK
Tel +44 20 7396 5572
Fax +44 20 7396 5599
Email: dimitri.dimitriou@dyodelta.com
Website: www.dyodelta.com
Relevant Publications
1) L. Kappos, G Comi, H. Panitch, J. Oger, J. Antel,
P. Conlon, L. Steinman & The Altered Peptide Ligand in relapsing MS
study group.
Induction of a non-encephalitogenic type 2 T
helper-cell antoimmune response in multiple sclerosis after administration
of an altered peptide ligand in a placebo controlled, randomized phase II
trial.
Nature Medicine, 2000, 6(10): 1176-1182.
2) B. Bielekova, B. Goodwin, N. Richert, I. Cortese,
T. Kondo, G. Afshar, B. Gran, J. Eaton, J. Antel, J. Frank, H. McFarland,
R. Martin.
Encephalitogenic potential of the myelin basic
protein peptide (amino-acids 83-99) in multiple sclerosis: results of a
phase II clinical trial with an altered peptide ligand.
Nature Medicine, 2000, 6(10): 1167-1171.
3) J. Pires, T. Tselios, J. Matsoukas, G. Moore.
Role of myelin basic protein epitope MBP74-85 in experimental
autoimmune encephalomyelitis: elaboration of agonist and antagonist
motifs.
Drug Development Research, 1999, 48: 1-5.
4) T. Tselios, L. Probert, I. Daliani, E. Matsoukas,
A. Troganis, I. Gerothanasis, T. Mavromoustakos, G. Moore, J. Matsoukas.
Design and synthesis of a potent cyclic analogue of
the myelin basic protein epitope MBP72-85: importance of the ala81
carboxyl group and of a cyclic conformation for induction of experimental
allergic encephalomyelitis (E.A.E.).
J. Med. Chem., 1999, 42, 7:1170-1177.
5) T. Tselios, I. Daliani, L. Probert, S. Deraos, E.
Matsoukas, S. Roy, J. Pires, G. Moore, J. Matsoukas.
Treatment of experimental allergic encephalomyelitis
(EAE) induced by guinea pig myelin basic protein epitope 72-85 with a
human MBP87-99 analogue and effects of cyclic peptides.
Bioorg. Med. Chem., 2000, 8: 1903-1909.
6) T. Tselios, I. Daliani, S. Deraos, S. Thymianou,
E. Matsoukas, A. Troganis, I. Gerothanassis, A. Mouzaki, T. Mavromoustakos,
L. Probert, J. Matsoukas.
Treatment of experimental allergic encephalomyelitis
(EAE) by a rationally designed cyclic analogue of myelin basic protein (MBP)
epitope 72-85.
Bioorg. Med. Chem. Lett., 2000, 10: 2713-2717.
7) T. Tselios, V. Apostolopoulos, I. Daliani,, S.
Deraos, S. Grdadolnik, T. Mavromoustakos, M. Melachrinou, S. Thymianou, L.
Probert, A. Mouzaki, J. Matsoukas. Antagonistic Effects of Human Cyclic
MBP87-99 Altered Peptide Ligands in Experimental Allergic
Encephalomyelitis and Human T-Cell Proliferation. J. Med. Chem. 2002, 45,
275-283.
Disease Overview
Multiple sclerosis (MS) is a chronic, potentially
debilitating disease potentially of autoimmune origin, that affects the
central nervous system. In
MS, natural defences like antibodies and white blood cells attack proteins
in the myelin sheath surrounding nerves in the brain and spinal cord,
causing inflammation and injury to the sheath and ultimately to the
nerves. This results in
multiple areas of scarring (sclerosis), affecting muscle coordination,
visual sensation and other nerve signals.
MS is a progressive disease and is generally diagnosed first in
people between the ages of 20 and 40.
Estimates range from 1 million to 2.5 million people affected with
MS worldwide, with a market of around $11 billion.
The disease is poorly understood.
