Probiodrug reports
full year 2017 financial results
-
PQ912 delivers positive
pharmacodynamic and efficacy results in a Phase 2a study in
early stage AD patients - data presented at
CTAD, Boston, November 2017
-
PQ912 Phase 2b core program
initiated
-
PQ912 demonstrates efficacy in
a preclinical Huntington's disease model
-
Unique binding mode of PBD-C06
to pGlu-Abeta peptides identified
-
Successful settlement of
pending tax issue
HALLE (SAALE),
Germany, 03 April 2018 Probiodrug AG (Euronext Amsterdam: PBD),
a clinical stage 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 2017 prepared in accordance with German GAAP ("HGB")
and, on a voluntary basis, in accordance with IFRS as endorsed by
the European Union. The Financial Statements 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
-
Phase 2a SAPHIR study results presented in
November 2017 at Clinical Trials on Alzheimer's Disease (CTAD),
Boston, USA
-
Initiation of PQ912 Phase 2b core program -
trial design based on new FDA draft guidelines and the new
guideline version of the EMA for early AD
-
PQ912 demonstrates efficacy in preclinical
Huntington's disease model
-
Publication of new results of PQ912 pharmacology
in peer reviewed journal
-
Positive results with PQ912 and PBD-C06 alone
and in combination in AD animal models presented
-
Unique binding mode of Probiodrug's
anti-pGlu-Abeta antibody PBD-C06 published in a peer reviewed
journal
-
Successful settlement of pending tax
liability
-
Annual Shareholders' Meeting held on 13 June
2017
-
Expenditures and corresponding cash position in
line with management expectations
-
Cash and cash equivalents of EUR 10.3 million as
of 31 December 2017, providing according to present projections a
cash reach through 2018
POST PERIOD
HIGHLIGHTS
Probiodrug made a presentation entitled "Inhibition of glutaminyl cyclase as a new concept for the
treatment of Alzheimer's disease: PQ912, the first-in-class
QC-inhibitor in clinical development for AD" at the 255th National
Meeting & Exposition of the American Chemical Society (ACS),
New Orleans, USA in March 2018.
CONFERENCE
CALL
Probiodrug will host a conference call open to the public today, 03
April 2018, at 15:00 Central European Summer Time (CEST) / 09:00
Eastern Daylight Times (EDT); the presentation will also be
available on the company website. The conference will be held in
English. A Question & Answer session will follow the
presentation of results.
To participate in the conference
call, please call one of the following numbers 10 minutes prior to
commencement.
Please dial one of the following
access numbers, then enter the PIN Code: 09533722#
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 |
UK |
08002794054 |
+442030092470 |
USA |
|
+18774230830 |
Commenting on the 2017 results,
Dr Konrad Glund, Chief Executive Officer of Probiodrug,
said:
"2017 has been a milestone year for Probiodrug. The positive
results of the PQ912 Phase 2a SAPHIR trial have ensured a big leap
forward in adding further validation and value to the program. The
strong efficacy signals obtained after only three months of
treatment support our concept of pGlu-Abeta being central for the
synaptic impairment and over-inflammatory status within the
continuum of the pathological process of AD.
"We are now in planning/ set-up
phase for a robust proof of concept Phase 2b program for PQ912
consisting of an EU and an US trial. The studies are designed in
accordance with the newest regulatory guidelines, also with a view
on the optionality of a conditional approval with convincing
positive Phase 2b data, and state of the art scientific concepts.
We are convinced that our stepwise rational development strategy
with clear objectives and hard state of the art cognition and
functional endpoints increases likelihood of success. We believe
the Phase 2a data and the next steps create interest and will
convince third parties to support the development of PQ912. The
implementation of the basis and securing the resources for the
execution of the programs are a key strategic goal for 2018."
KEY FIGURES
(ACCORDING TO IFRS)
in EUR
k, unless otherwise stated |
2017 |
2016 |
Earnings, Financial and Net Assets
Position |
|
|
Operating loss |
-9,961 |
-13,777 |
Finance income/loss |
850 |
-114 |
Income tax gain |
1,102 |
0 |
Net
loss for the period |
-8,009 |
-13,891 |
Equity (end of the
year) |
8,923 |
16,376 |
Equity ratio (end of the year) (in %) |
82.9 % |
73.2 % |
Balance sheet total
(end of the year) |
10,762 |
22,366 |
Cash
flows used in operating activities (year) |
-12,117 |
-13,255 |
Cash flows used in
operating activities (monthly average) |
-1,010 |
-1,105 |
Cash
flows used in investing activities (year) |
459 |
-124 |
Cash
flows provided by financing activities (net) |
127 |
13,915 |
Cash
and cash equivalents at the end of period |
10,291 |
21,897 |
|
|
|
Personnel |
|
|
Total number of
employees (incl. Board of management)
(end of the year) |
14 |
13 |
Average number of employees
(incl. Board of management) |
13.3 |
14.5 |
|
|
|
Probiodrug-Share |
|
|
Loss per share (basic
and diluted) (in EUR) |
-0.98 |
-1.82 |
Number of shares issued (end of the year) |
8,208 |
8,187 |
DETAILS OF THE
FINANCIAL RESULTS (ACCORDING TO IFRS)
Net
loss
The net loss amounts to EUR 8,009k (2016: EUR 13,891k), thereof EUR
9,961k (2016: EUR 13,777k) operating loss, which is partly offset
by EUR 850k (2016: EUR -114k) financial income and EUR 1,102k
(2016: EUR 0k) income from tax gain. The majority of the operating
loss is due to the research and development expenses amounting to
EUR 7,454k (2016: EUR 10,951k), whereas the general and
administrative expenses of EUR 2,511k (2016: EUR 2,909k) represent
the smaller fraction thereof. The financial income amounting to EUR
850k and the income taxes gain amounting to EUR 1,102k result from
the successful settlement of the potential tax liability from the
financial year 2004. All expenditures are in line with the
projections of Probiodrug.
Equity
The equity amounts to EUR 8,923k (2016: EUR 16,376k), leading to an
equity ratio of 82.9%. In 2017, the share capital increased by
21,274 shares from the conditional capital 2010 via the exercise of
outstanding stock options. By this the share capital increased from
EUR 8,186,735 to EUR 8,208,009.
Cash
The cash flow used in investing activities shows proceeds from the
expiration of a pension liabilities insurance in the amount of EUR
467k (2016: EUR 0k) and costs in intangible assets and equipment in
the amount of EUR 8k (2016: EUR 124k). Cash and cash equivalents at
year end 2017 were EUR 10,291k (2016: EUR 21,897k).
Noncurrent/
current liabilities
The noncurrent liabilities with EUR 1,171k (2016: EUR 850k)
represent the net commitment (defined benefit liability) of the
pension commitments (defined benefit obligations) of EUR 1,619k
(2016: EUR 1,644k). The current liabilities decreased
significantly and amounted to EUR 668k (2016: EUR 5,140k) as
at 31 December 2017. The decrease in the current liabilities is
mainly driven by the successful settlement of the potential tax
liability and the decrease of the trade payables. According to the
settlement, Probiodrug paid in total (taxes including accrued
interest) an amount of EUR 775k and released the remaining
provision of EUR 1,964k. The trade payables amounting to EUR 344k
(2016: EUR 1,893k) result 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 (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
Phase I
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.
Phase 2a
PQ912 is the first QC-inhibitor being tested in patients. In
January 2017 Probiodrug announced the completion of the recruitment
for the SAPHIR Phase 2a study of PQ912 in early Alzheimer's disease
patients. The randomized, double-blind multi-center study enrolled
120 patients with early stage Alzheimer's disease, surpassing the
110 patients planned in the study protocol. 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. In April 2017
Probiodrug announced the Last Patient Last Visit (LPLV) reached in
the SAPHIR Study.
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.
In June 2017 Probiodrug
communicated positive pharmacodynamic and efficacy results of PQ912
in the Phase 2a SAPHIR Study. The SAPHIR study was the first
clinical trial to investigate PQ912 in patients with early AD over
a treatment period of 12 weeks. The highest dose of 800mg bid PQ912
used in the Phase 1 multiple dose study was applied and 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. Regarding
safety overall no major safety concern associated with PQ912 was
raised. There were no significant differences in the number of AE
or SAE between active and control arm. A significantly higher
number of patients discontinuing within first weeks of treatment
with PQ912 compared to placebo was observed; there were clinically
relevant differences in the number of patients with skin and GI
effects. These events appeared early in the study and were fully
reversible. Safety and tolerability are likely to be improved by
lower dose, still showing a high enzyme inhibition, and a slower
titration regime. In summary 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.
In October 2017 Probiodrug
announced the initiation of the Phase 2b core program for PQ912 and
detailed the strategy. The Phase 2b core program is planned to
comprise of two complementary clinical Proof of Concept studies in
Europe and the USA. The development strategy has built in the
newest FDA and EMA draft guidance for early AD trials as published
in February 2018.
The 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.
Combination therapies
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.
Huntington's disease
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.
PBDC06 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 PBDC06.
PBD-C06 revealed a unique binding
mode, published in August 2017 in the Journal of Biological
Chemistry (Piechotta et al., 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.
Publications
13th
International Conference on Alzheimer's and Parkinson's Diseases
(AD/PDTM 2017),
Vienna, Austria: In March 2017 Probiodrug presented an oral
presentation entitled: "Selective targeting of
pGlu-Abeta with an IgG2a 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".
The data resulted from a collaboration between Probiodrug and
Harvard, BWH, Boston, USA. Additionally, two posters were
presented:
-
"In CSF from AD patients high
correlation of QC activity with AD related biomarkers and
inflammatory molecules were found" in cooperation with the
VUmed Center Amsterdam, The Netherlands and
-
"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" in cooperation with
Fraunhofer Institute, Halle (Saale), Germany.
Journal of Pharmacology and Experimental
Therapeutics: In May 2017 Probiodrug announced the
publication of a PQ912 pharmacology paper entitled "Glutaminyl Cyclase Inhibitor PQ912 improves cognition in
mouse models of Alzheimer's disease - studies on relation to
effective target occupancy" in a peer-reviewed journal (T.
Hofmann et al. Journal of Pharmacology and Experimental
Therapeutics April 26, 2017, jpet.117.240614; DOI:
https://doi.org/10.1124/jpet.117.240614))..
Journal of Biological Chemistry: In August 2017 the
unique binding mode of PBD-C06 to pGlu-Abeta peptides was published
("Structural and functional analyses of
pyroglutamate-amyloid-ß-specific antibodies as a basis for
Alzheimer immunotherapy"; Piechotta et al. J. Biol. Chem. 2017
292:12713). 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.
CTAD 2017, Boston, USA: In November 2017 Prof
Philip Scheltens, MD, PhD, Principal Investigator of the SAPHIR
study, presented the data from this trial during the Late Breaking
Oral Communications session at the CTAD 2017. The presentation was
entitled "Phase 2a study results with the
glutaminylcyclase inhibitor PQ912 in early Alzheimer's
Disease".
Partnerships
In December 2017 Probiodrug and dutch company Crossbeta Biosciences
B.V. extended their strategic partnership in the field of
Alzheimer's disease biomarkers in order to utilize Crossbeta's
proprietary technology to support of Probiodrug's biomarker
development activities.
CORPORATE
REVIEW
General Meeting
of Shareholders of Probiodrug AG on 13 June 2017
All resolutions proposed by the Company's Management and
Supervisory Board were approved at the meeting with a large
majority:
-
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
-
Election of the 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
The general shareholder meeting on 13 June 2017 re-elected Dr Erich
Platzer, Dr Dinnies von der Osten and Dr Jörg Neermann. The
Supervisory Board then re-elected Dr Erich Platzer as chairman and
Dr Dinnies von der Osten as vice chairman.
Mr Kees Been resigned from his
board position in November 2017 for personal reasons.
POST PERIOD
HIGHLIGHTS
255th National
Meeting & Exposition of the American Chemical Society (ACS),
New Orleans, USA: Dr Ulrich Heiser, Director Medicinal
Chemistry/CMC gave a presentation entitled "Inhibition of glutaminyl cyclase as a new concept for the
treatment of Alzheimer's disease: PQ912, the first-in-class
QC-inhibitor in clinical development for AD" in March 2018.
OUTLOOK
The mid-term focus of Probiodrug's business
activities can be summarised as follows:
-
Execution of the Phase 2b clinical study program
for PQ912
-
Continuing the development of PBD-C06
-
Conclusion of one or more industrial
partnerships
-
Further scientific analysis of potential second
indications for the use of QC-inhibitors
-
Further strengthening Probiodrug's financial
resources.
Probiodrug projects a net loss for
the financial year 2018 which, based on the current budget, is
expected to be lower than that of 2017.
ANNUAL FINANCIAL
REPORT 2017
Probiodrug has finalized its
financial statements for the year ended 31 December 2017 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
15 May 2018 |
Interim
Management Statement Q1 2018 |
21 June
2018 |
Annual
General Meeting 2018 |
30 August
2018 |
Interim
Report, Half Year Results 2018 |
29
November 2018 |
Interim
Management Statement Q3 2018 |
###
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, Kelly Mueller
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 clinical stage 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) as a therapeutic strategy. Its lead product, PQ912,
has successfully completed a Phase 2a (SAPHIR) study. The company's
pipeline also includes PBD-C06, an anti-pGlu-Abeta-specific
monoclonal antibody, in preclinical development. Probiodrug 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.
About
PQ912
PQ912, is a first in class, highly specific and potent inhibitor of
Glutaminyl Cyclase (QC), the enzyme catalyzing the formation of
synaptotoxic pGlu-Abeta. PQ912 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 with >90%
target occupancy in the spinal fluid. In June 2017, Probiodrug
announced top-line data of the Phase-2a SAPHIR trial of PQ912 and
presented the study results at CTAD 2017. Results strongly support
(a) the hypothesis of pGlu-Abeta being synaptotoxic and (b) the
therapeutic concept pursued by Probiodrug. The study 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 initiated the preparation of a Phase 2b core program.
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. 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. Today, 47
million people live with dementia worldwide, and this number is
projected to treble to more than 131 million by 2050, as the global
population ages. 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.