Unique binding
mode of PBD-C06 to pGlu-Abeta peptides identified
Probiodrug
publishes mechanism of target binding for its lead anti-pGlu-Abeta
monoclonal antibody PBD-C06
HALLE (SAALE),
Germany, 29 August 2017 - Probiodrug AG (Euronext
Amsterdam: PBD), a biopharmaceutical company developing novel
therapeutic solutions to treat Alzheimer's disease (AD), announced
today that results from a collaboration between Probiodrug, the
Fraunhofer Institute for Cell Therapy and Immunology (IZI),
Department of Drug Design and Target Validation (IZI-MWT, HalleS.)
and a team led by Dr. Milton T. Stubbs at the
Martin-Luther-Universität Halle-Wittenberg (MLU) were published in
the Journal of Biological Chemistry (Piechotta et
al,. J. Biol. Chem. 2017 292:12713). In these studies, the
binding characteristics of a murine version of Probiodrug's lead
therapeutic antibody (PBD-C06) against its designated target
pGlu-Abeta was analyzed at the molecular level applying
co-crystallization and X-ray structure analysis. The studies
revealed a unique binding mode of PBD-C06 to pGlu-Abeta peptides,
which are believed to catalyze the seeding of synapto/neurotoxic
Abeta oligomers, a key culprit in the pathology of AD.
Furthermore, the data provide a rationale for the high target
specificity of PBD-C06 and suggest low binding to off-targets, such
as unmodified, less toxic Abeta peptides.
These insights reveal a
differentiating biological property of PBD-C06 compared to other
anti-Abeta antibodies and further support the development of
PBD-C06. PBD-C06 is a humanized and deimmunized monoclonal antibody
selected based on an optimal safety and pharmacological profile.
CMC development for PBD-C06 has been initiated.
Prof. Dr. Milton
T. Stubbs from the Institute for Biochemistry und Biotechnology at
the MLU commented: "The results explain why the unique
structure of pGlu-Abeta can facilitate enhanced aggregation of
Abeta oligomers. Specific targeting of pGlu-Abeta with antibodies
could eliminate neurotoxic pGlu-Abeta containing oligomers in the
brain. PBD-C06 thus has a promising therapeutic potential".
Dr. Inge Lues,
PBD's Chief Development Officer, added: "These results provide
differentiating insights into the biology of PBD-C06, allowing a
better understanding of how PBD-C06 interacts with its target at
the molecular level. Importantly, they support the nomination
of PBD-C06 as an optimal candidate for further development.
Probiodrug is progressing two
complementary strategies for tackling pGlu-Abeta with two
candidates in development: PQ912, a small molecule inhibitor of
Glutaminyl Cyclase, now in Phase 2, and PBD-C06, a
pGlu-Abeta-specific monoclonal antibody in preclinical stage.
###
For more
information please contact:
Probiodrug
Dr Konrad Glund, CEO
Email: contact@probiodrug.de
Hume
Brophy
Conor Griffin, Alexander Protsenko, Jonothan Blackbourn
Tel: +44 (0) 20 7862 6381
Email: probiodrug@humebrophy.com
The Trout
Group
Tricia Truehart
Tel: +1 (646) 378-2953
Email: ttruehart@troutgroup.com
MC Services AG
Anne Hennecke, Caroline Bergmann
Tel: +49 (0) 211 529 252 20
Email: probiodrug@mc-services.eu
Notes to
Editors:
About Probiodrug
AG
Headquartered in Halle (Saale),
Germany, Probiodrug AG (Euronext Amsterdam: PBD) is a
biopharmaceutical company focused on the development of new
therapeutic products for the treatment of Alzheimer's disease (AD).
Probiodrug has identified a new therapeutic concept linked to
disease initiation and progression. The development approaches are
targeting a key neuro/synaptotoxic component of the pathology,
pyroglutamate-Abeta (pGlu-Abeta, N3pG) as a therapeutic
strategy.
Probiodrug's lead product
candidate, PQ912, is a highly specific and potent inhibitor of
Glutaminyl Cyclase (QC), which has shown therapeutic effects in AD
animal models. A Phase 1 study in healthy young and elderly
volunteers revealed a dose dependent exposure and showed good
safety and tolerability up to the highest dose showing >90%
target occupancy in the spinal fluid. In June 2017 Probiodrug
announced top-line data of the Phase 2a SAPHIR trial of its lead
candidate (Probiodrug announces encouraging results of the Phase 2a
SAPHIR Study). The positive effects seen on secondary exploratory
efficacy markers are strongly supporting (a) the hypothesis of
pGlu-Abeta being synaptotoxic and (b) the therapeutic concept
pursued by Probiodrug. The study revealed a positive benefit risk
ratio of PQ912 and provides important guidance how to move forward
in the development of PQ912 as a disease-modifying drug for AD.
Altogether, the results make the program highly attractive for
further development.
Complementary to the small
molecule PQ912 inhibiting the formation of the synaptotoxic agent
pGlu-Abeta, the company is developing PBD-C06, an
anti-pGlu-Abeta-specific monoclonal antibody.
The Company has medical use and composition of matter patents
related to the inhibition of QC and anti-pGlu-Abeta-specific
monoclonal antibodies, and has, in the Company's view, a leading
position in this field of research.
Founded in 1997 by Hans-Ulrich
Demuth and Konrad Glund, the company successfully developed a novel
therapeutic concept for diabetes - the DP4 inhibitors - which
provided the basis for a novel class of antidiabetics - the
gliptins. Its core capabilities are based on its long-standing
expertise in the elucidation of the structure and function of
enzymes involved in the modification of proteins and peptides,
which play a central role in pathological conditions.
Today, Probiodrug aims to become a
leading company in the development of AD treatments and to thereby
provide a better life for Alzheimer's disease patients.
www.probiodrug.de
About Alzheimer's
disease
Alzheimer's disease is a neurological disorder, which is the most
common form of dementia, and ultimately leads to death. Because
Alzheimer's disease cannot be cured and is degenerative, the
affected patients must increasingly rely on others for assistance.
Today, 47 million people live with dementia worldwide, and this
number is projected to treble to more than 131 million by 2050, as
populations age. Dementia also has a huge economic impact.
Alzheimer's has an estimated, global societal cost of US$ 818
billion, and it will become a trillion dollar disease by 2018.
(World Alzheimer Report 2016).
Forward Looking
Statements
Information set forth in this press release
contains forward-looking statements, which involve a number of
risks and uncertainties. The forward-looking statements contained
herein represent the judgment of Probiodrug AG as of the date of
this press release. Such forward-looking statements are neither
promises nor guarantees, but are subject to a variety of risks and
uncertainties, many of which are beyond our control, and which
could cause actual results to differ materially from those
contemplated in these forward-looking statements. We expressly
disclaim any obligation or undertaking to release publicly any
updates or revisions to any such statements to reflect any change
in our expectations or any change in events, conditions or
circumstances on which any such statement is based.