This is
a correction of the announcement from 06:00 30.11.2017 GMT. Reason
for the correction:
> As of 30 September
2017, Probiodrug held EUR 11.70 million in cash and cash
equivalents, providing according to present projections a cash
reach through 2018
HALLE (SAALE),
Germany, 30 November 2017 - Probiodrug AG (Euronext Amsterdam:
PBD), a biopharmaceutical company developing novel therapeutic
solutions to treat Alzheimer's disease (AD), today announces its
third quarter business update for the period ending 30 September
2017, in the form of an interim management report.
The interim management report for
the third quarter 2017 is available to download on the company
website
(http://www.probiodrug.de/investors/reports-and-presentations/).
OPERATIONAL HIGHLIGHTS
-
Unique binding mode of Probiodrug`s
anti-pGlu-Abeta antibody PBD-C06 published in a peer reviewed
journal
-
Expenditures and corresponding cash position in
line with management expectations
-
As of 30 September 2017,
Probiodrug held EUR 11.70 million in cash and cash equivalents,
providing according to present projections a cash reach through
2018
POST PERIOD HIGHLIGHTS
-
Phase 2b core program of PQ912 initiated and
details of further strategy outlined
-
Data of Probiodrug`s Phase 2a SAPHIR Study
presented in November 2017 at CTAD in Boston, USA - the world
congress for clinical trial results in AD
-
Change at supervisory board
Commenting on the third quarter, Dr Konrad Glund,
Chief Executive Officer of Probiodrug, said:
"Probiodrug is strongly engaged
and committed to further progress its highly innovative and
differentiated concept of targeting a toxic Abeta variant,
pGlu-Abeta, for the treatment of AD with PQ912, a first in class
small molecule Glutaminyl Cyclase inhibitor in Phase 2, and
PBD-C06, a pGlu-Abeta specific monoclonal antibody in advanced
preclinical development.
"As for PQ912, results of the
phase 2a (SAPHIR) study provided important guidance for designing a
core Phase 2b program consisting of trials planned to be conducted
in Europe and the US. The preparation of the European trial has
been initiated. In parallel to initiating Phase 2b, we are
continuing pharma interactions.
"PBD-C06, our pGlu-Abeta specific
monoclonal antibody, has the potential of being a best in class
compound. The molecule is designed to bind aggregated pGlu-Abeta
with high affinity and specificity while having a reduced potential
for side effects and immunogenicity. We recently published a unique
binding mode of this antibody to pGlu-Abeta explaining its
extraordinary affinity and specificity. Results have been obtained
using crystal structure analysis within a collaboration of
Probiodrug with academic groups."
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 formation 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, NL 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 data of the Phase 2a SAPHIR
Study were presented by Prof Philipp Scheltens, Principal
Investigator of this study, at the CTAD in Boston, USA in November
2017. The presentation was entitled "Phase 2a
study results with the glutaminylcyclase inhibitor PQ912 in early
Alzheimer's Disease".
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
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 of 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
(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. The next step is the Phase 2b
core program, for which preparation started in October 2017.
This Phase 2b core program will
consist of two clinical trials, to be executed in the European
Union (EU) and the USA, respectively. The first Phase 2b study is
intended to investigate the safety and efficacy of the optimal dose
range of PQ912 in early AD patients. This trial will build on the
excellent and efficient infrastructure which was established for
the Phase 2a SAPHIR study. Moreover, it is based on the valuable
results of the SAPHIR study and has been designed with the guidance
of international KOLs in the Alzheimer's field. Prof Philip
Scheltens, MD PhD, Director of the Alzheimer Center VU University
Medical Center Amsterdam, NL will once again serves as Principal
Investigator and Chairperson for this study, which is to be
conducted in the EU. A second complementary study is currently in
the planning phase and is intended to be carried out in the USA and
will also be chaired by a highly renowned Principal
Investigator.
Probiodrug is also working on
potential combination therapies. Here, 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 March 2017.
Probiodrug is exploring potential
second indications for its QC inhibitors. PQ912 demonstrated
beneficial effects in a preclinical Huntington's disease (HD)
model; the data of this study have been presented at the
12th Annual HD
Therapeutics Conference of the CHDI Foundation, Malta, in
April 2017. 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 changes, metabolic and neuropathological signs
of the disease become visible. 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, the energy
metabolism as well as 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.
PBD-C06 revealed a unique binding
mode, which was published in August 2017 in the Journal of
Biological Chemistry (Piechotta et a,. J. Biol.
Chem. 2017 292:12713).
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
Operational
Update
Unique binding
mode of PBD-C06 to pGlu-Abeta published in August
2017
In these studies, the binding characteristics of a murine version
of Probiodrug's lead therapeutic antibody (PBD-C06) against its
designated target pGlu-Abeta was analyzed at the molecular level
applying co-crystallization and X-ray structure analysis. The
studies revealed a unique binding mode of PBD-C06 to pGlu-Abeta
peptides, which are believed to catalyze the seeding of
synapto/neurotoxic Abeta oligomers, a key culprit in the pathology
of AD. Furthermore, the data provide a rationale for the high
target specificity of PBD-C06 and suggest low binding to
off-targets, such as unmodified, less toxic Abeta peptides.
These insights reveal a
differentiating biological property of PBD-C06 compared to other
anti-Abeta antibodies and further support the development of
PBD-C06.
The results from a collaboration
between Probiodrug, the Fraunhofer Institute for Cell Therapy and
Immunology (IZI), Department of Drug Design and Target Validation
(IZI-MWT, Halle(S)) and a team led by Dr Milton T. Stubbs at the
Martin-Luther-Universität Halle-Wittenberg (MLU) were published in
the Journal of Biological Chemistry (Piechotta et
al,. J. Biol. Chem. 2017 292:12713) in August 2017.
Financials
Research and development expenses in the third quarter of 2017 were
EUR 1,127k, lower than the corresponding numbers in 2016 (EUR
1,776k) due to the completion of the Phase 2 study (SAPHIR study)
of PQ912. General administrative expenses amounted to EUR 526k
compared to EUR 588k in the third quarter of 2016, which is in line
with the company's expectations. As expected, the company did not
generate any revenue in the third quarter of 2017. Overall, the
company's loss is EUR 1,656k in the third quarter of 2017, compared
to EUR 2,383k in the third quarter of 2016, mainly due to lower
research and development expenses.
The corresponding comprehensive
loss for the 9-month period from 1 January to 30 September 2017
amounts to EUR 5,962k, which is significantly lower than for the
same period of 2016 (EUR 8,427k). The difference of EUR 2,465k
is mainly driven by the release of tax provisions (EUR 1,964k)
following the agreement with the relevant authorities about the
corporate income and trade tax claim for the assessment period
2004.
As of 30 September 2017,
Probiodrug held EUR 11.7 million in cash and cash equivalents,
providing according to present projections a cash reach through
2018.
All numbers are in line with
management expectations.
POST PERIOD UPDATE
Probiodrug
provided update regarding its Phase 2b core program of PQ912 and
further corporate strategy in October 2017
Probiodrug initiated the preparation of the Phase 2b core program
of PQ912 in October 2017. This Phase 2b core program will consist
of two clinical trials, to be executed in the European Union (EU)
and the USA, respectively.
The first Phase 2b study is
intended to investigate the safety and efficacy of the optimal dose
range of PQ912 in early AD patients. This trial will build on the
excellent and efficient infrastructure which was established for
the Phase 2a SAPHIR study. Moreover, it is based on the valuable
results of the SAPHIR study and has been designed with the guidance
of international KOL`s in the Alzheimer's field. Prof. Philip
Scheltens MD PhD, Director of the Alzheimer Center VU University
Medical Center Amsterdam, NL will once again serves as Principal
Investigator and Chairperson for this study, which is to be
conducted in the EU.
A second complementary study is
currently in the planning phase and is intended to be carried out
in the USA and will also be chaired by a highly renowned Principal
Investigator.
Probiodrug is in parallel
progressing with its interaction with potential pharma partners to
secure one or more transactions around its pipeline.
Prof Philipp
Scheltens, Principal Investigator of the Phase 2a SAPHIR Study,
presented the data of this study at CTAD 2017 - the world congress
for clinical trial results in Alzheimer`s Disease (AD) - in Boston,
USA in November 2017
Prof Philip Scheltens, MD, PhD, Principal Investigator of the
study, presented during the Late Breaking Oral Communications
session at the CTAD in Boston, USA in November 2017. The
presentation was entitled "Phase 2a study results
with the glutaminylcyclase inhibitor PQ912 in early Alzheimer's
Disease".
Supervisory Board
changes
Mr Kees Been resigned from his board position in November 2017 for
personal reasons. The management and supervisory board expressed
their gratitude for Kees' contribution and support in the last two
years.
###
For more
information please contact:
Probiodrug
Dr Konrad Glund, CEO
Email: contact@probiodrug.de
Optimum Strategic
Communications
Mary Clark, Supriya Mathur, Hollie Vile
Tel: +44 (0) 203 714 1787
Email: Probiodrug@OptimumComms.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 and presented the study results at CTAD in Boston on 1
November 2017 in Boston. 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. The company has meanwhile
initiated the preparation of a Phase 2b core program.
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
global 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.
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