Probiodrug AG
Announces Acceptance of PQ912 Pharmacology Paper by Peer Reviewed
Journal
HALLE (SAALE),
Germany, 16 May 2017 - Probiodrug AG (Euronext Amsterdam: PBD),
a biopharmaceutical company developing novel therapeutic solutions
to treat Alzheimer's disease (AD), today announces that a paper
concerning the pharmacological profile of its lead product
candidate, the QC inhibitor PQ912, has been accepted by the
peer-reviewed Journal of Pharmacology and Experimental
Therapeutics. The paper is entitled:
'Glutaminyl
Cyclase Inhibitor PQ912 improves cognition in mouse models of
Alzheimer's disease - studies on relation to effective target
occupancy'
Authored by T. Hofmann et al.
Journal of Pharmacology and Experimental Therapeutics April 26,
2017, jpet.117.240614; DOI:
https://doi.org/10.1124/jpet.117.240614
Inge Lues, Chief
Development Officer at Probiodrug commented: These animal data
are an important component of target validation and translation
into the clinic. Together with the pharmacokinetic/pharmacodynamic
data obtained in the MAD Phase 1 study with PQ912 they have been
very important in guiding our decision for dose selection in the
Phase 2 SAPHIR study. Due to the good safety and tolerability
profile of PQ912 demonstrated in Phase 1 we selected a dose which
would result, on average, in a target occupancy of about 90%.
SAPHIR Phase 2 results are expected to be available in Q2 this
year.
Context: The
majority of Abeta peptides deposited in Alzheimer's Disease (AD)
are truncated and post-translationally modified at the N-terminus.
Among these, pyroglutamyl-Abeta (pE-Abeta or N3pE-Abeta) has been
identified as particularly neurotoxic. N-terminal pE modification
increases the peptide's hydrophobicity, reduces susceptibility to
degradation by peptidases and strongly accelerates formation of
neurotoxic amyloid beta oligomers, which have been shown to impair
synaptic integrity and brain connectivity, physiological substrates
for cognitive functions. It has been shown that the formation of
pE-Abeta is strictly dependent on glutaminyl cyclase activity (QC).
Thus, inhibiting QC activity is an attractive option to treat AD
pursued by Probiodrug.
Results and
conclusions:
-
In this paper, we present data about the
pharmacological in vitro and in vivo efficacy of the QC-inhibitor PQ912, the
first-in-class compound that is in clinical development.
-
PQ912 QC-activity of various species with
Ki-values in the
range between 20 and 65 nM.
-
Chronic oral treatment of hAPPSLxhQC
double transgenic mice applying PQ912 via chow (200 mg/kg/day) demonstrates a significant reduction of
brain-pE-Abeta levels and concomitant improvement of spatial
learning in a Morris water maze test paradigm.
-
The dose used resulted in a brain and CSF
(cerebrospinal fluid) concentration of PQ912 which relates to a QC
target occupancy of on average about 60 %.
Thus, we conclude that > 50 % inhibition of QC activity in the
brain leads to robust treatment effects. Secondary pharmacology
experiments in mice indicate a fairly large potency difference for
glutamate cyclisation of Abeta compared to glutamine cyclisation of
physiological substrates, suggesting a robust therapeutic window in
humans. These results constituted an important translational
guidance for predicting the therapeutic dose range in clinical
studies with PQ912.
###
For more
information, please contact:
Probiodrug
Dr Konrad Glund, CEO
Email: contact@probiodrug.de
Hume
Brophy
Conor Griffin, Jonothan Blackbourn, Alexander Protsenko
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.
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 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.