Combination therapy with Glutaminyl Cyclase (QC) inhibitor
PQ912 and pGlu-Abeta specific antibody PBD-C06 shows clear additive
effects in reducing pGlu-Abeta as well as Abeta in Alzheimer-mouse
model
HALLE(SAALE),
Germany, 13 September 2016 - Probiodrug AG (Euronext Amsterdam:
PBD), a biopharmaceutical company developing novel therapeutic
solutions to treat Alzheimer's disease (AD), announced today first
results of a preclinical combination trial targeting
pGlu-Abeta.
An additive effect on lowering
pGlu-Abeta (pyroglutamate-Abeta) as well as total Abeta was
observed with a double-pronged approach of targeting toxic
pGlu-Abeta by combining the Glutaminyl Cyclase-inhibitor PQ912 to
block pGlu-Abeta formation and the mouse version of the pGlu-Abeta
specific antibody, PBD-C06, to increase clearance in an AD animal
model.
The combination study was
performed in a well-characterized double transgenic Alzheimer
animal model, APPswlhQC. In
independent pre-studies the single agents showed a dose-dependent
effect on lowering pGlu-Abeta and total Abeta. In the combination
study in parallel cohorts, efficacy was compared for low dose of
each single agent and the same doses in combination. Therapeutic
treatment started at eight months of age, after the onset of
pathology, and continued for four months. The combination was very
well tolerated. No signs of intolerability or toxicity were
observed. Pharmacodynamic effects on pGlu-Abeta and total Abeta was
captured by ELISA and by IHC (immunohistochemistry).
While there was a modest reduction
in pGlu-Abeta and total Abeta following low dose treatment with
each single agent, there was a significant reduction in pGlu-Abeta
and total Abeta in the combination-treated mice. According to the
Bliss model, the combination results correspond to a strong
additive effect. The combination prevented the 10-fold increase of
pGlu-Abeta observed in control animals during the treatment period.
Selected doses of the single agents led to about 35% reduction in
hippocampal pGlu-Abeta plaque load whereas the combination
treatment significantly reduced plaque load by about 65%. It is
important to emphasize that specific targeting of pGlu-Abeta by
combination treatment also reduced total Abeta.
Data were generated in
collaboration with Cynthia Lemere of Brigham and Women's Hospital,
Harvard Medical School, and QPS, Graz, Austria.
Commenting on the
announcement, Dr Inge Lues, CDO of Probiodrug, said:
"Considering the complex Alzheimer's pathology, therapeutic
progress will likely be very much facilitated by combination
strategies, as in other indications. Our results are very exciting
as they clearly indicate an attractive approach for combination by
either increasing the effect size on lowering toxic pGlu-Abeta and
total Abeta as shown here, or potentially by lowering a single
agent's dose when combined to avoid limiting safety issues. Other
combinations of interfering with pGlu-Abeta and Abeta are currently
running."
Cynthia Lemere,
Scientist at Brigham and Women's Hospital, added: "These data
are exciting because they indicate that although both approaches
may work as monotherapies, they are likely to have even greater
potential if these two complementary approaches are combined."
For more
information please contact:
Probiodrug
Dr Konrad Glund, CEO
Email: contact@probiodrug.de
Hume
Brophy
Supriya Mathur, Eva Haas, Alexia Faure
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, over 46 million people worldwide currently live with the
condition and this number is expected to increase to 132 million by
2050. Alzheimer's also has an estimated, global societal cost of
US$ 818 billion (World Alzheimer Report 2015).
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.