Probiodrug AG
reports First Quarter 2017 Business Update
HALLE (SAALE),
Germany, 12 May 2017 - Probiodrug AG (Euronext Amsterdam:
PBD), a biopharmaceutical company developing novel therapeutic
solutions to treat Alzheimer's disease (AD), today announces
its first quarter business update for the period ending 31 March
2017, in the form of an interim management report.
The interim management report for
the first quarter 2017 is available for download on the
company
website (http://www.probiodrug.de/investors/reports-and-presentations/).
OPERATIONAL
HIGHLIGHTS
- New, promising results from pharmacological
studies with PQ912 and PBD-C06 in AD animal models and an
evaluation of new biomarkers in cerebrospinal fluid (CSF) from AD
patients presented
- Expenditures and corresponding cash position in
line with management expectations
- As of 31 March 2017, Probiodrug held EUR 18.7
million in cash and cash equivalents
POST PERIOD
HIGHLIGHTS
- Last Patient Last Visit (LPLV) reached in the
SAPHIR Study
- The Glutaminyl Cyclase (QC) inhibitor PQ912
demonstrates beneficial effects in a preclinical Huntington`s
disease model
Commenting on the
first quarter, Dr Konrad Glund, Chief Executive Officer of
Probiodrug, said:
"In the first quarter of 2017 we successfully continued to execute
on our corporate strategy. The Last Patient Last Visit (LPLV)
represents an important step towards the conclusion of our first
patient trial with PQ912. The promising data obtained with PQ912
and PBD-C06 in AD animal models further demonstrates the potential
of the pGlu-Abeta treatment concept. Positive treatment results
with PQ912 in a Huntington's disease animal model provide support
for evaluating PQ912 in patients with Huntington`s disease
(HD) in the future, another neurological disease based on misfolded
proteins."
OPERATIONAL
REVIEW
Pipeline
update
Probiodrug`s therapeutic approach targets pyroglutamate-Abeta
(pGlu-Abeta, also called N3pG Abeta) as a therapeutic strategy
to fight Alzheimer's disease. This modified Abeta is considered to
be linked with disease initiation and progression by seeding the
formation of soluble neurotoxic amyloid oligomers. Probiodrug is
developing proprietary product candidates to target toxic
pGlu-Abeta via two modes of action: by (i) inhibiting the
production of pGlu-Abeta; and (ii) clearing existing pGlu-Abeta
from the brain.
Probiodrug's innovative approach
is based on the development of specific inhibitors for the enzyme
Glutaminyl Cyclase (QC), which is instrumental in the creation of
pGlu-Abeta. In addition, the company is developing a monoclonal
antibody targeting pGlu-Abeta to enhance its clearance.
To date, Probiodrug's pipeline
consists of two small molecule inhibitors of the QC-enzyme, PQ912
and PQ1565, and a monoclonal antibody, PBD-C06, targeting
pGlu-Abeta.
PQ912
Probiodrug is running a Phase 2a trial, the "SAPHIR" study, of its
lead product candidate PQ912. In a preceding Phase 1 study with
healthy young and elderly volunteers, PQ912 was shown to be safe
and well tolerated and revealed high QC-inhibition.
PQ912 is the first QC-inhibitor
being tested in patients. The Phase 2a study is a randomized,
double-blind multi-center study which plans to enrol a total of 110
patients with early stage Alzheimer's disease. The study is led by
internationally renowned experts in AD in seven European countries
at 21 sites, with the Alzheimer Center, VU Medical Center
(VUmc), Amsterdam being the lead center. The primary endpoint of
the trial is the safety and tolerability of PQ912 compared with
placebo over a three-month treatment period. Additionally, a set of
exploratory read-outs comprising cognitive tests, functional
assessments by EEG and functional MRI and new molecular biomarkers
in CSF will be used to evaluate the compound's effect on the
pathology of the disease.
In this study Mini-Mental State
Examination (MMSE) and the Cogstate neuro-psychological test
battery (NTB) are monitored blindly every 30 patients to ensure
consistency and reliability of ratings. First blinded results at
baseline show that the mean MMSE scores from the 120 randomised
patients is 25.3, the mean age is 73 years and gender distribution
is 64 female and 56 male. Current results indicate a low
variability and therefore the high quality of the assessments being
used.
Recruitment has been completed in
mid-December 2016. A total of 120 patients have been randomised,
surpassing the 110 patients planned in the study protocol. Full
unblinded results of the SAPHIR study are expected in the second
quarter of 2017.
PBD-C06
PBD-C06 is a monoclonal antibody, currently in preclinical stage.
PBD-C06 targets pGlu-Abeta, aiming to selectively clear the brain
of pGlu-Abeta while leaving non-toxic forms of Abeta untouched.
PBD-C06 has been successfully humanized and also de-immunized to
avoid detection by the patient's endogenous immune system. For the
first time for an anti-pGlu-Abeta approach PBD-C06 has not only
shown the ability to reduce Abeta/plaques but also to significantly
improve cognitive deficits in aged Alzheimer's mice. Moreover, no
evidence was found of increased microhemorrhages after treatment
with PBD-C06.
The development of the
manufacturing process of this molecule is running.
PQ1565
PQ1565 is a QC-inhibitor, currently in preclinical stage. The
product candidate has shown attractive drug-like properties in
preclinical studies. The GMP process for this molecule is being
implemented.
The next development steps are in
preparation and respective decisions would be made in connection
with the readout of the SAPHIR trial.
Operational
Update
New promising
results from pharmacological studies with PQ912 and PBD-C06 in AD
animal models and an evaluation of new
biomarkers in cerebrospinal fluid (CSF) from AD patients
presented
Three updates on the advancement
of its product candidates and the results of a Biomarker research
collaboration have been presented at the 13th International
Conference on Alzheimer's and Parkinson's Diseases
(AD/PDTM 2017),
Vienna, Austria. The conference took place from 29th March
to 2nd April
2017.
Program |
Presentations |
QC- enzyme/CSF Biomarker
Collaborator:
VUmed Center Amsterdam, The Netherlands |
-
Cerebrospinal fluid glutaminyl cyclase (QC)
activity correlates with Alzheimer's disease biomarkers and
inflammation molecules in AD patients
-
In CSF from AD patients a high
correlation of QC activity with AD related biomarkers and
inflammatory molecules was found
|
QC-Inhibitor PQ912
Collaborator:
Fraunhofer Institute, Halle (Saale),
Germany |
-
Glutaminyl cyclase inhibition by PQ912 in
transgenic mice with Alzheimer-like pathology-translation to
clinics
-
Based on PKPD analysis in
animal studies, a 50% inhibition of QC activity in the brain leads
to a robust effect - an important translational guidance for
therapeutic dosing in clinical studies
|
Anti-pGlu-Abeta MAB/QC-I
Collaborator:
Harvard, BWH, Boston, USA |
-
Murine anti-pyroglutamate-3 Abeta MAB, 07/2a,
spares cognition, reduces plaques, and, in combination with
glutaminyl cyclase inhibitor PQ912, further improves efficacy
-
Selective targeting of
pGlu-Abeta with an IgG2a isotype of an anti-pyroglutamate-3-Abeta
Antibody in tg mice is effective in lowering plaque
pathology and improving cognition. A combination of
a QC-inhibitor and a pGlu-Abeta specific antibody showed
superior efficacy compared to the single entities
|
CORPORATE
REVIEW
Financials
The first quarter of 2017 showed an increase of research and
development expenses to EUR 2,268k compared to EUR 1,974k in the
first quarter of 2016, reflecting mainly the costs for the Phase 2
trial (SAPHIR Study) of PQ912. General and administrative expenses
amounted to EUR 507k compared to EUR 597k in the first quarter of
2016, reflecting more intrayear shifts than actual savings. In the
first quarter 2017 the Company has not generated any revenues,
also in line with the corporate planning. Correspondingly, the
comprehensive loss of the reporting period was EUR 2,798k, compared
to EUR 2,596k in the first quarter of 2016.
All results are in line with
management expectations.
Probiodrug held EUR 18.7 million
in cash and cash equivalents as of 31 March 2017.
POST PERIOD
UPDATE
Last Patient Last
Visit (LPLV) accomplished in the SAPHIR Study
On 07 April 2017 Probiodrug announced that the Last Patient's Last
Visit (LPLV) occurred on 05 April 2017 in the currently
running Phase 2a SAPHIR study investigating the QC-inhibitor
PQ912.
PQ912
demonstrates beneficial effects in a preclinical Huntington`s
disease model
On 10 April 2017 Probiodrug announced results of a preclinical
study targeting Glutaminyl Cyclases (QCs) in Huntington`s disease
(HD). The results have been presented at the 12th Annual
HD Therapeutics Conference of the CHDI Foundation on 23rd of
April in St. Julian's, Malta. HD is the most common inherited
neurodegenerative disorder where, due to a mutation, the
poly-glutamine amino acid sequence is expanded in a protein called
huntingtin (HTT). There is currently no disease modifying therapy
for this condition.
PQ912 clearly improved several
signs of the disease in a well characterized BACHD mouse model of
HD. BACHD mice carry the human gene for mutant HTT (mHTT). At six
weeks old, parallel to the onset of first behavioral, metabolic and
neuropathological signs of the disease, the BACHD mice were treated
for 18 weeks with food pellets containing PQ912. PQ912 treatment
for 18 weeks caused a significant reduction (approximately
30%) in brain mHTT levels. These lowered mHTT levels were
associated with reduced levels of the inflammation/gliosis marker
GFAP-protein, a striking normalization of the abnormal body weight
gain and energy metabolism as well as a normalization of several
mRNA levels coding for HSPs in BACHD mice at 24 weeks of age.
Data were generated in
collaboration with Stephan von Hörsten of the University Hospital
Erlangen, part of Friedrich-Alexander-University (FAU), Erlangen,
Germany.
Invitation to
Probiodrug`s Ordinary General Meeting of Shareholders on 13 June
2017
On 03 May 2017 Probiodrug invited its shareholders to its ordinary
general meeting of shareholders to be held on Tuesday, 13 June 2017
at 11:00 am (CEST), at the Mercure Hotel MOA Berlin, Stephanstraße
41, 10559 Berlin, Germany. The relevant documents can be found
at http://www.probiodrug.de/investors/annual-shareholders-meeting-2017/.
###
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.