Amyloid-beta
(Abeta) aggregate-clearing by the murine anti-pyroglutamate-3 Abeta
IgG2a monoclonal antibody PBD-C06 with and without a complement
mutation in an Alzheimer's mouse model
HALLE (SAALE),
Germany, 16 November 2016 - Probiodrug AG (Euronext Amsterdam:
PBD), a biopharmaceutical company developing novel therapeutic
solutions to treat Alzheimer's disease (AD), announced today the
first results of a preclinical study in an AD mouse model with the
pyroglutamate-3 Abeta (pGlu3-Abeta)-specific antibody mPBD-C06,
comparing versions with and without a mutation eliminating
complement activation which will be presented as a poster at the
Society for Neuroscience (SfN) meeting on 16 November 2016 in San
Diego, CA.
Data were generated in
collaboration with Cynthia Lemere of Brigham and Women's Hospital,
Harvard Medical School, and QPS, Graz, Austria.
Previously, Lemere's team showed
that the mouse IgG2a variant of the anti-pGlu3-Abeta monoclonal
antibody was more effective at clearing Abeta aggregates and
rescued behavioral deficits compared to the mouse IgG1 version (SfN
2015). In the present study, the effect of eliminating the
antibody's ability to activate complement (CDC) on the efficiency
to reduce Abeta plaques was investigated and it was found that both
variants - with and without CDC - reduced pGlu3-Abeta as well
as general Abeta to the same extent - without inducing
microhemorrhages. Thus, avoiding complement activation did not
impact the capacity of mPBD-C06 to eliminate pGlu3-Abeta
aggregates. In addition, microglial activation was assessed
in vivo by 18F-GE180 TSPO
microPET imaging at baseline and following a single injection of
the pGlu3-Abeta antibody variants. In contrast to the IgG2a
variant, which showed enhanced whole brain uptake of 18F-GE180 in AD
mice, the antibody lacking CDC did not alter the TSPO signal after
injection.
In summary, the data demonstrate
for the first time, that microglial activation, analyzed by TSPO
microPET, can be reduced by CDC inactivation without impairing the
potency of the antibody to clear amyloid deposits. Further studies
are underway to better understand the clearance mechanisms for each
of these anti-pGlu3 Abeta antibodies.
Inge Lues, Chief
Development Officer of Probiodrug, commented: "These data are
very exciting as they demonstrate efficient Abeta clearance without
potential side- or dose-limiting effects of inducing
inflammation."
Cynthia Lemere,
PhD, scientist at Brigham and Women's Hospital, added:
"Although further investigation is needed, these early data suggest
that the novel CDC-mutant anti-pGlu3 Abeta antibody may improve
efficacy and safety as an AD immunotherapy." Lemere is currently
the recipient of pre-clinical sponsored research from Probiodrug
AG.
###
For more
information please contact:
Probiodrug
Dr Konrad Glund, CEO
Email: contact@probiodrug.de
Hume
Brophy
Mary Clark, Supriya Mathur, Eva Haas
Tel: +44 (0) 207 862 6475
Email: probiodrug@humebrophy.com
The Trout
Group
Tricia Truehart
Tel: +1 646 378-2953
Email: ttruehart@troutgroup.com
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.
Founded in 1997, 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's aim is to
become a leading company in the development of Alzheimer's disease
treatments and to thereby provide a better life for Alzheimer's
disease patients. It has identified a new therapeutic concept
linked to disease initiation and progression. The development
approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a
therapeutic strategy to fight Alzheimer's disease. The Company has
medical use and composition of matter patents related to the
inhibition of Glutaminyl Cyclase (QC) and anti-pGlu-Abeta- specific
monoclonal antibodies, providing it, in the Company's view, with a
leading position in this field of research.
Probiodrug's lead product
candidate, PQ912, is a highly specific and potent inhibitor of
Glutaminyl Cyclase (QC), which has shown therapeutic effects in
Alzheimer's animal models. PQ912 is currently in a Phase 2a study,
the SAPHIR trial. In a preceding Phase 1 study with healthy young
and elderly volunteers, PQ912 has shown to be safe and well
tolerated and also revealed high QC-inhibition.
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 also 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.