Probiodrug reports
full year 2016 financial results
SAPHIR, the Phase 2a study of
PQ912 as a novel treatment for Alzheimer's disease fully
enrolled
Favourable results of chronic
toxicology studies with PQ912 announced
Promising combination data of
PQ912 and a pGlu Abeta specific antibody
generated
Successful capital raise of EUR
14.9 million with blue chip investors completed
HALLE (SAALE),
Germany, 30 March 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 twelve-month period ending 31 December 2016
prepared in accordance with German GAAP ("HGB") and, on a voluntary
basis, in accordance with IFRS as endorsed by the European Union.
The Annual Reports are available on the company website
(http://www.probiodrug.de/investors/reports-and-presentations/).
KEY HIGHLIGHTS
-
Favourable results of chronic toxicology studies
with Glutaminyl Cyclase (QC) inhibitor PQ912 announced
-
Encouraging combination data of PQ912 with
pGlu-Abeta specific antibody PBD-C06 generated
-
Innovative Phase 2 study design of PQ912 in
early Alzheimer's disease presented
-
SAPHIR Phase 2 study of PQ912 fully enrolled in
December 2016
-
Promising new findings for Probiodrug's
Glutaminyl Cyclase - inhibitor in an inflammation animal model
announced
-
Abeta aggregate-clearing by PBD-C06 with and
without complement mutation in an Alzheimer's mouse model
announced
-
Key patents on Glutaminyl Cyclase (QC)
inhibition, PQ912 and the pGlu-Abeta targeting monoclonal antibody
program for the treatment of Alzheimer's disease granted
-
Capital raise of EUR 14.9 million executed in
October 2016
-
Cash and cash equivalents of EUR 21.9 million as
of 31 December 2016
-
Net loss of EUR 13.9 million compared with EUR
13.5 million in 2015 - in line with company expectations
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,
March 30, at 15:00 Central European Summer Time (CEST); 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 the PIN Code: 17545699#
Country |
Toll-Free |
Toll/Local |
Austria |
0800301051 (EN)
0800301052 (DE) |
+4319280492 (EN)
+4319280494 (DE) |
Belgium |
|
+32 11500307 |
Canada (Toronto) |
|
+1
4162164186 |
Finland |
0800523161 |
+35 8981710496 |
France |
0805110449 |
+33
170750705 |
Germany (Frankfurt) |
08006270715 |
+49 69222229043
(EN)
+49 69222229044 (DE) |
Luxemburg |
080040184 |
+35
227300157 |
Netherlands |
|
+31 107137273 |
Sweden |
0200883629 |
+46
850556469 |
Switzerland |
0800005200
(EN)
0800005205 (DE) |
+41 225805970
(EN)
+41 225805971 (DE) |
UK |
|
+44
2030092452 |
USA |
|
+1
8554027766 |
A Question and Answer session will
follow the presentation of results.
Dr Konrad Glund,
Chief Executive Officer of Probiodrug comments on the 2016
results: "We look back to a very successful year. Significant
progress was made with our lead molecule PQ912 - we could announce
favourable long term toxicology data, exciting preclinical data of
combining our two target approaches, a QC inhibitor with an anti
pGlu-Abeta antibody, and, finally, the full enrolment of the Phase
2 "SAPHIR" study. We trust that the advancement of the program
further increases the attractiveness of PQ912 and strengthens the
foundation for decisions on further clinical studies.
The recent failures of several
late stage clinical studies in AD clearly indicate that more
focused and specific approaches targeting selectively the
neurotoxic fraction of Abeta are needed. Innovative treatment
strategies should address pathological processes such as synaptic
failure and impairment of neuronal connectivity underlying clinical
symptoms. Here Probiodrug's differentiated approach of targeting
specifically toxic pGlu-Abeta via QC inhibition and/or via specific
anti-pGlu-Abeta antibodies offers attractive new strategies to
tackle AD.
With our capital raise from
October 2016 we welcomed a number of new blue-chip investors. The
successes of 2016 were only possible with the high support, trust
and commitment of all stakeholders and we would like to take the
opportunity to say many thanks to all of you."
KEY FIGURES
(ACCORDING TO IFRS)
in EUR
k, unless otherwise stated |
2016 |
2015 |
Earnings, Financial and Net Assets
Position |
|
|
Operating loss |
-13,777 |
-13,393 |
Net
loss for the period |
-13,891 |
-13,505 |
Equity (end of the
year) |
16,376 |
16,133 |
Equity ratio (end of the year) (in %) |
73.2 % |
73.8 % |
Balance sheet total
(end of the year) |
22,366 |
21,866 |
Cash
flows used in operating activities (year) |
-13,255 |
-12,147 |
Cash flows used in
operating activities (average) |
-1,105 |
-1,012 |
Cash flows used in
investing activities (year) |
-124 |
-10 |
Cash
flows provided by financing activities (net) |
13,915 |
12,598 |
Cash and cash
equivalents at the end of period |
21,897 |
21,361 |
|
|
|
Personnel |
|
|
Total number of
employees (incl. Board of management)
(end of the year) |
13 |
16 |
Average number of employees
(incl. Board of management) |
14.5 |
15.8 |
|
|
|
Probiodrug-Share |
|
|
Loss per share (basic
and diluted) (in EUR) |
-1,82 |
-1.97 |
Number of shares issued (end of the year) |
8,187 |
7,442 |
DETAILS OF THE
FINANCIAL RESULTS (ACCORDING TO IFRS)
Net
loss
The net loss amounts to EUR 13,891k (2015: EUR 13,505k), thereof
EUR 13,777k (2015: EUR 13,393k) operating loss and EUR 114k (2015:
EUR 112k) financial loss. The majority of the operating loss is
determined by the research and development expenses amounting to
EUR 10,951k (2015: EUR 10,158k), whereas the general and
administrative expenses of EUR 2,909k (2015: EUR 3,279k) represent
a minor fraction thereof. All numbers are in line with the
projections of Probiodrug.
Equity
The equity amounts to EUR 16,376k (2015: EUR 16,133k), resulting in
an equity ratio of 73.2%.
Cash
Cash and cash equivalents were EUR 21,897k (2015: EUR 21,361k). Net
cash proceeds of EUR 13,915k were realised in the course of
the capital increase in October 2016.
Noncurrent/
current liabilities
The noncurrent liabilities with EUR 850k (2015: EUR 822k) represent
the net commitment (defined benefit liability) of the pension
commitments (defined benefit obligations) of EUR 1,644k (2015:
EUR 1,522k). The current liabilities are nearly constant with
EUR 5,140k versus EUR 4,911k at the end of 2015 and consist
primarily of tax liabilities and trade payables. The tax liability
of EUR 2,739k results from payment obligations as a result of the
tax audit for the period 2002 through 2005 including interest for
late payment. The trade payables amount to EUR 1,893k (2015: EUR
1,629k) resulting from of the ordinary course of business. They
have a remaining term of up to one year.
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 tests 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.
Publications/
Presentations
In March 2016 Probiodrug presented at the 14th AAT
Symposium on Advances in Alzheimer Therapy in Athens Greece two
oral presentations entitled "The pyroglutamate modification of
toxic A-beta resulted in new therapeutic approaches: Inhibitors of
glutaminyl cyclase and highly specific antibodies - A status
report" and "Phagocytic characterization and therapeutic efficacy
of an Anti-PyroGlutamate-3 A-beta IgG2a antibody in aged APP/PS1dE9
mice". The data resulted from a collaboration between Probiodrug
and a research team led by Professor Hans-Ulrich Demuth from the
Department of Drug Design and Target Validation at the Fraunhofer
Institute for Cell Therapy and Immunology IZI, Halle (Saale),
Germany and the research team led by Professor Cynthia Lemere from
the Center for Neurologic Diseases at the Brigham and Women's
Hospital and Harvard Medical School, Boston, MA, USA.
In April 2016 Probiodrug announced
that it has concluded the assessment of its chronic toxicology
studies with its lead candidate PQ912, currently under development
for AD in a clinical Phase 2 study (SAPHIR). The results showed
that the toxicology profile of PQ912 in the 6-month rat and 9-month
dog studies was absolutely comparable to the results of the
previously available 3-month toxicology studies conducted in the
same species. No new findings were observed and the minimal to
slight non-adverse or questionable changes seen in both the 1-month
- and the 3 month-studies were not aggravated after prolonged
treatment, thus providing an excellent basis for a sound
preclinical safety assessment. In conclusion, the comfortable
safety margin is retained.
In May 2016 Probiodrug presented
two poster at the 1st Meeting of
the newly founded Society for CSF Analysis and Clinical
Neurochemistry in Gothenburg, Sweden entitled "Quantitative
Analysis of truncated Abeta peptide substrates of glutaminyl
cyclase in human CSF samples using LC-MS/MS," and "Determination of
Abeta Oligomers using a Flow Cytometry-Förster Resonance Energy
Transfer (FRET) method,". Probiodrug is evaluating and establishing
new concept-related molecular biomarkers to be used in their
ongoing Phase 2a study (SAPHIR). The emphasis is regarded as an
important and key cornerstone in the read out hierarchy in clinical
studies.
In June 2016 Probiodrug announced
an agreement with the Dutch biotech company Crossbeta Biosciences
B.V. in order to utilize Crossbeta's proprietary technology in
support of Probiodrug's biomarker development activities. The
potential of Crossbeta's unique technology has significant impact
to overcome the challenge of establishing and validating sensitive
and specific assays for Abeta- and pGlu-Abeta-oligomers to be used
in the clinical studies of Probiodrug's lead candidate, Glutaminyl
Cyclase (QC) inhibitor PQ912.
In September 2016 new findings for
Probiodrug's Glutaminyl Cyclase - inhibitor in an inflammation
animal model were presented at the Summer Frontiers Symposium 2016
'Systems Biology of Innate Immunity', Nijmegen, The Netherlands and
the 6th European
Workshop on Lipid Mediators, Frankfurt/M, Germany. The data
resulted from a collaboration between Probiodrug and Ambiotis. The
effect of the QC inhibitor PQ912 was investigated in a mouse
model of inflammation (thioglycollate induced peritonitis) with
special focus on its effect on cell infiltration and release of
pro-resolving lipid mediators. The effects seen with PQ912 on
recruitment of macrophages and eosinophils, and levels of
chemokines and lipid mediators, makes QC inhibition attractive for
further evaluation as potential anti-inflammatory drug and/or
resolution promoting agent.
Also in September 2016 Probiodrug
announced 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 its clearance in an AD animal
model
In November 2016 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 were
presented as a poster at the Society for Neuroscience (SfN) meeting
in San Diego, CA, USA. The data were generated in collaboration
with Cynthia Lemere of Brigham and Women's Hospital, Harvard
Medical School, and QPS, Graz, Austria. It was demonstrated 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.
In December 2016 the Innovative
Phase 2 study design of the SAPHIR study was presented at
9th Clinical
Trials on Alzheimer's disease (CTAD), San Diego, CA, USA. Based on
an exploratory analysis of 86 randomised patients, a low
standard deviation for the Neuro-psychological test battery and
functional EEG at baseline has been observed. The SAPHIR study has
been designed and is conducted in collaboration with Philip
Scheltens, M.D., Ph.D., the VUmc Amsterdam (NL) and the CRO Julius
Clinical (NL).
Patents
In 2016, Probiodrug's IP position was further strengthened by
important patent applications being granted. These include:
-
Patents US 9,156,907 and JP 5,828,762 covering
antibody program targeting pyroglutamate Abeta (pGlu-Abeta, also
N3pG Abeta) in the US and in Japan, method as well as
composition of matter claims.
-
Patent JP 5,934,645 covers PQ912 and surrounding
chemical space; this patent has been granted already in the USA,
the EU as well as in other important markets. With a patent life
expiring in 2030, plus the usual extension for pharmaceuticals, the
patent provides a solid protection for PQ912 in Japan and other key
markets.
-
Patent JP 5,930,573 covers the general use of QC
inhibitors for the treatment of Mild Cognitive Impairment (MCI),
granted previously for the treatment of AD and
British/Danish dementia in the USA, EU and Japan, thereby
broadly protecting the general use of QC inhibition. Importantly,
the granted claims of JP 5,930,573, already issued in the US,
complement and extend the use of QC inhibitors for MCI.
CORPORATE
REVIEW
Execution of a
capital increase via accelerated bookbuild
On October 6, 2016 Probiodrug announced an increase in its share
capital from EUR 7,442,487 to EUR 8,186,735, by issuing 744,248 new
shares generating gross proceeds of EUR 14.9 million. The order
book was well covered based on strong demand from European and US
investors. The new shares were placed with selected qualified
institutional investors at a price of EUR 20 per share. The issued
shares represented approximately 10% of the Company's issued share
capital at the time of the placing.
Executive
Management
Mark Booth, who was appointed as Chief Business Officer in March
2016, left the company for personal reasons in August 2016 and his
responsibilities have been taken over by Dr Konrad Glund, CEO.
Supervisory
Board
The general shareholder meeting on May 19, 2016, re-elected Dr
Erich Platzer, Dr Dinnies von der Osten, Dr Jörg Neermann and Dr
Olivier Litzka as Supervisory Board Members. The Supervisory Board
then re-elected Dr Erich Platzer as chairman and Dr Dinnies von der
Osten as vice chairman.
Dr Olivier Litzka, partner at
Edmond de Rothschild Investment Partners (EdRIP) and member of the
Supervisory Board since October 2009, stepped down in September
2016 as part of a natural transition.
OUTLOOK
The mid-term focus of Probiodrug's business
activities can be summarised as follows:
-
Continuing the clinical development of PQ912, in
particular generate initial patient study data in 2017 and start
long-term treatment,
-
Continuing the development of PBD-C06,
-
Continuing the development of PQ 1565,
-
Further scientific analysis of potential second
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.
As a result of the continuing costs being incurred
for development activities, the Company projects a net loss for the
financial year 2017 which may be lower than that incurred in
2016.
ANNUAL FINANCIAL
REPORT 2016
Probiodrug has finalized its
financial statements for the year ended 31 December 2016 according
to German GAAP ("HGB") and IFRS. The auditor KPMG has issued an
unqualified auditors report for both statements. The reports are
available on the company website
(http://www.probiodrug.de/investors/reports-and-presentations/).
FINANCIAL
CALENDAR
12 May 2017 |
Interim
Management Statement Q1 2017 |
13 June
2017 |
Annual
General Meeting 2017 |
31 August
2017 |
Interim
Report, Half Year Results 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, Alexia Faure, 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.