Probiodrug reports
financial results for H1 2017 and corporate update
PQ912 delivers positive pharmacodynamic and efficacy
results in a Phase-2a study in early stage AD
patients
Successful settlement of
long-pending tax issue
PQ912 demonstrates efficacy in a
preclinical Huntington`s disease model
HALLE (SAALE), Germany, 31 August
2017 - Probiodrug AG (Euronext Amsterdam: PBD), a
biopharmaceutical company developing novel therapeutic solutions to
treat Alzheimer's disease (AD), today announced its financial
results for the first six months ending 30 June 2017, prepared in
accordance with German GAAP ("HGB") and, on a voluntary basis, in
accordance with IFRS as endorsed by the European Union. The reports
are available on the company website
(http://www.probiodrug.de/investors/reports-and-presentations/).
KEY HIGHLIGHTS
- PQ912 delivers positive pharmacodynamic
and efficacy results in a Phase-2a study, the SAPHIR study, in
early stage AD patients
- Successful settlement of the potential tax
liability resulting from 2004
- PQ912 demonstrates efficacy in preclinical
Huntington`s disease model
- Publication of PQ912 pharmacology paper in a
peer-reviewed journal: 'Glutaminyl Cyclase Inhibitor PQ912 improves
cognition in mouse models of Alzheimer's disease - studies on
relation to effective target occupancy'
- New positive results with PQ912 and PBD-C06 alone
and in combination in AD animal models presented
- Annual Shareholders' Meeting held on 13 June
2017
- Expenditures and corresponding cash position in
line with management expectations
- As of 30 June 2017, Probiodrug held EUR 14.4
million in cash and cash equivalents
POST PERIOD HIGHLIGHTS
There were no significant events
subsequent to the reporting period.
CONFERENCE CALL
Probiodrug will host a conference
call open to the public today at
15:000 Central European Summer Time (CEST)/
09:00 am Eastern Daylight Time (EDT); the presentation will also be
posted to the website. The conference will be held in English. To
participate in the conference call, please call one of the
following numbers ten minutes prior to commencement:
Please dial one
of the following access numbers, then enter your PIN
Code: 48432861#
A Question & Answer session will follow the presentation of results.
Dial in coordinates
Country |
Toll-free |
Toll/Local |
Austria |
0800005804 |
+4319286161 |
Belgium |
080058130 |
+3224019516 |
Canada (Toronto) |
18552409492 |
+14162164179 |
Finland |
800778964 |
+358981710375 |
France |
0805639972 |
+33170709502 |
Germany (Frankfurt) |
08008050102
(DE)
08008050115 (EN) |
+4969201744220
(DE)
+4969201744210 (EN) |
Luxemburg |
080040194 |
+35227302111 |
Netherlands |
08000200293 |
+31207168020 |
Sweden |
0200885102 |
+46850644386 |
Switzerland |
0800001875 |
+41445806522 |
United Kingdom |
08002794054 |
+442030092470 |
USA |
|
+18774230830 |
Commenting on the
results, Dr Konrad Glund, Chief Executive Officer of Probiodrug
said:
"Within the first half of 2017 we have done a significant step
forward in the development of our AD program. In June we announced
top-line data of the Phase-2a SAPHIR trial of our lead compound
PQ912.
The results show a high target
occupany, a lowering of pGlu-Abeta oligomers and indicate positive
effects on synaptic function, as measured by changes of biomarker,
EEG and on a test of working memory. These data clearly support the
hypothesis of pGlu-Abeta being synaptotoxic and the effect of
Glutaminyl Cyclase (QC)-inhibitors on reversing this pathology. The
data are highly valuable for guiding the further development of
PQ912 as a disease-modifying drug for AD.
The beneficial effects of PQ912 in
a preclinical Huntington`s disease model further strengthen the
case to address this devastating disease as an additional
indication for our QC inhibitors. The positive results
with PQ912 and PBD-C06 in AD animal models further increase the
attractiveness of our data package.
Moreover, we could solve the tax
topic, which was pending since 2008 and was absorbing significant
resources and attention. This is a great achievement.
With its extensive data base
generated, Probiodrug seems well positioned to explore partnering
options."
KEY FIGURES
(ACCORDING TO IFRS)
|
Jan - June 2017 |
Jan - June 2016 |
Jan - Dec 2016 |
In EUR
k, unless otherwise stated |
|
|
|
Earnings, Financial and Net Assets
Position |
|
|
|
Operating loss |
-6,262 |
-5,987 |
-13,777 |
Income from release of tax provision |
1,956 |
0 |
0 |
Net loss for the
period |
-4,306 |
-6,044 |
-13,891 |
Equity (end of the reporting period) |
12,211 |
10,465 |
16,376 |
Equity ratio (end of
the reporting period) (in %) |
81.6% |
66.6% |
73.2
% |
Balance sheet total (end of the reporting period) |
14,971 |
15,740 |
22,366 |
Cash flows from
operating activities (cum.) |
-7,508 |
-7,000 |
-13,255 |
Cash
flows from operating activities
(monthly average) |
-1,251 |
-1,167 |
-1,105 |
Cash flows from
financing activities (net) |
0 |
0 |
13,915 |
Cash
and cash equivalents at the end of the reporting period |
14,385 |
14,245 |
21,897 |
|
|
|
|
Personnel |
|
|
|
Total number of
employees(incl. Board of management)
(end of the reporting period) |
14 |
16 |
13 |
Probiodrug-Share |
|
|
|
Loss per share
(basic/diluted) (in EUR) |
-0,53 |
-0,81 |
-1,82 |
Number of shares issued
(end of the reporting period) |
8,187 |
7,442 |
8,187 |
DETAILS OF THE
FINANCIAL RESULTS (ACCORDING TO IFRS)
The comparison figures for the
first six months 2017 shown below refer to the corresponding 2016
numbers.
Net
loss
The net loss amounts to EUR 4,306k (Jan - June 2016: EUR 6,044k).
EUR 6,262k (Jan - June 2016: EUR 5,987k) are to be attributed to
the operating loss, EUR 856k to the financial income (Jan - June
2016: EUR 57k financial loss) and EUR 1,100k (Jan - June 2016: EUR
0k) to the gain from income taxes. The financial income and the
gain from income taxes result from the successful settlement
of the potential tax liability from the financial year 2004 (see
Corporate Review). The operating loss is primarily driven by
research and development expenses amounting to EUR 4,937k (Jan
- June 2016: EUR 4,711k) and to a lesser degree
by the general and administrative expenses of EUR 1,329k (Jan
- June 2016: EUR 1,325k). The slight increase
in research and development expenses reflects primarily the
development activities of PQ912. These expenditures are
in line with the expectations of Probiodrug.
Equity
As of 30 June 2017, the equity amounts to EUR 12,211k (as of 31
December 2016: EUR 16,376k), corresponding to an equity ratio of
81,6% (as of 31 December 2016: 73.2%).
Cash
Cash and cash equivalents were EUR 14,385k compared with EUR
21,897k as of 31 December 2016.
Noncurrent/
current liabilities
The noncurrent liabilities amount to EUR 859k (as of 31 December
2016: EUR 850k), consisting completely of the net commitment
(defined benefit liability) of the pension commitments. The current
liabilities amount to EUR 1,901k (as of 31 December 2016: EUR
5,140k), consisting mainly of trade payables in amounts of EUR
1,655k (as of 31 December 2016: EUR 1,893k), resulting from of the
ordinary course of business. They have a remaining term of up to
one year.
The decrease of the current
liabilities is mainly driven by successful settlement of the
potential tax liability. According to this settlement, Probiodrug
paid in total (taxes including accrued interest) in an amount of
EUR 775k, thereof EUR 9k paid in July 2017, and could release the
remaining provision of EUR 1,964k.
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 (AD). 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's lead product candidate, PQ912, is a highly specific
and potent inhibitor of QC, which has shown therapeutic effects in
AD-animal models. In a Phase-1 study with healthy young and elderly
volunteers, PQ912 was shown to be safe and well-tolerated and also
revealed a dose dependent QC-inhibition in the CSF, reaching
90 % at the highest dose used.
PQ912 is the first QC-inhibitor
being tested in patients. The Phase-2a study, the SAPHIR trial, was
a randomized, double-blind multi-center study which enrolled a
total of 120 patients with early stage Alzheimer's disease. The
study was 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 was 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 were used to evaluate the compound's
effect on the pathology of AD, in particular the effect on synaptic
impairment, an early pathological change in the early stages
of AD.
The SAPHIR trial used a high dose
of PQ912 (which showed 90% QC-enzyme inhibition in CSF in
Phase-1) in order to find both
- early-on tolerability signs and
- first signals on various sensitive secondary
exploratory outcome measures in a relatively short time frame.
With respect to the primary
endpoints there were no statistically significant differences
of PQ912 vs placebo between the number of patients experiencing an
adverse event or a serious adverse event. Patients in the treatment
arm did show a significantly higher discontinuation rate due to SAE
or grade 3 adverse events compared to patients in the placebo arm
and the total number of patients non-adherent to randomised
treatment for any reason was higher in the treatment arm. Skin and
gastrointestinal organ system related adverse events were observed
in a higher frequency in the PQ912 arm compared to placebo and
occurred in the majority in the first half of the treatment period.
Dose reductions prescribed by the investigator were identical in
the treatment and the placebo arm. With a view on the high
dose applied, Probiodrug is confident that with lower doses showing
still quite high levels QC-inhibition and a slower titration scheme
the drug will be safe and well-tolerated in AD patients
With respect to the secondary
exploratory endpoints PQ912 showed a very strong target engagement
(QC inhibition), confirming the finding in Phase-1 in elderly
healthy volunteers of more than 90%, significant improvements of
one test of working memory (one back test ) and a clear trend in
detection test (attention domain). At the functional level a very
significant positive effect was found on the EEG theta power.
Regarding exploratory biomarkers in the spinal fluid, encouraging
results in the right direction on synaptic and inflammatory CSF
markers were obtained.
In summary, the positive effects
on secondary exploratory efficacy markers are strongly supporting
of (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 pf PQ912 as a disease-modifying
drug for AD. Altogether, the results make the program highly
attractive for further development.
New positive results with PQ912
and PBD-C06 alone and in combination in AD animal models have been
presented at the 13th International Conference on Alzheimer's and
Parkinson's Diseases (AD/PDTM 2017), Vienna, Austria. In addition
an evaluation of exploratory biomarkers in cerebrospinal fluid
(CSF) from AD patients has also been presented.
PQ912 demonstrates beneficial
effects in a preclinical Huntington's disease model, which have
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.
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 compound is ready for regulatory
toxicology studies.
CORPORATE REVIEW
Settlement of the potential tax
liability resulting from the financial year 2004
In the reporting period the company could successfully reach an
agreement with the relevant authorities of Saxony-Anhalt about the
corporate income and trade tax claim for the assessment period
2004.
Following a tax audit in 2008, the
tax authorities retroactively increased the taxable profits for
2004 by approximately EUR 10 million, resulting in a potential tax
liability including accrued interest payment of a total of approx.
EUR 2.7 million as of the end of 2016. Probiodrug believed
that the better arguments spoke against the tax authorities' view
and had contested the claims of the tax authorities. The matter was
pending with the competent tax court. While still being convinced,
that the better arguments were on its side, Probiodrug was seeking
a solution with the relevant tax authorities of Saxony-Anhalt,
which ultimately was reached in the first half of 2017. According
to this settlement, Probiodrug paid in total (taxes including
accrued interest) an amount of EUR 775k.
With this step Probiodrug brought
this long-pending topic to its conclusion and could thereby prevent
a further distraction of its attention and resources.
Annual
Shareholders' Meeting 2017
On 13 June 2017, Probiodrug held its 2017 Annual Shareholders'
Meeting. All resolutions proposed by the Company's Management and
Supervisory Board were approved at the meeting, including:
- Adoption of a resolution on the approval of the
actions of the management board members for the financial year
2016
- Adoption of a resolution on the approval of the
actions of the supervisory board members for the financial year
2016
- Appointment of the statutory financial statements
auditor for the financial year 2017
- Elections to the supervisory board
- Resolution on the creation of the Authorized
Capital 2017 concurrently cancelling the Authorized Capital 2014 as
well as the corresponding amendments to the Articles of
Association
- Resolution on the specification of the number of
the Supervisory Board members as well as the corresponding
amendment to the Articles of Association
Supervisory Board
Dr Erich Platzer, Dr Dinnies von der Osten and Dr Jörg Neermann
were re-elected as members of the Supervisory Board, with Dr
Platzer being appointed as chairman and Dr von der Osten being
appointed as vice-chairman and Chairman of the Audit
Committee.
OUTLOOK
The mid-term focus of Probiodrug's business
activities can be summarised as follows:
- Continuing the clinical development of PQ912 with
a focus on dose dependency and a longer treatment period,
- Exploring partnering options,
- Continuing the development of PBD-C06,
- Further scientific analysis of potential
additional indications for the use of QC inhibitors,
- Further increasing visibility and acceptance as
an important prerequisite for obtaining additional capital as well
as for an industrial transaction,
- Further strengthening Probiodrug's financial
resources.
FINANCIAL STATEMENTS
January to June 2017
Probiodrug has finalized its
financial statements for the first six months 2017 according to
German GAAP ("HGB") and IFRS. The auditor KPMG has reviewed
the IFRS statements. The reports are available on the company
website
(http://www.probiodrug.de/investors/reports-and-presentations/).
Financial
calendar 2017
30
November 2017
Interim Management Statement Q3 2017
###
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.