-
Launch of AclarusDx™ (formerly EHT Dx21) on track for the end of 2009
-
Discussions ongoing to out-license EHT 0202
Regulatory News:
ExonHit Therapeutics (Paris:ALEHT) yesterday presented clinical data on
the validation set “Alzheimer patients versus healthy controls” for
AclarusDx™ (formerly EHT Dx21), its blood-based diagnostic test for the
detection of Alzheimer’s disease (AD), at the 2nd Conference
of Clinical Trials on Alzheimer’s Disease (CTAD) in Las Vegas, USA. This
set of data will support the launch of a test designed to differentiate
AD patients from healthy individuals and will be the first assay of the
AclarusDx™ product line.
“Many challenges exist today with respect to the clinical diagnosis
of AD patients,” stated Peter J. Snyder, M.D., Ph.D., Vice President
for Research for Lifespan and a Professor of Clinical Neurosciences at
the Warren Alpert Medical School of Brown University, Providence, Rhode
Island. “Moreover, there is a strong unmet need on the part of
pharmaceutical companies to utilize reliable, valid and cost-effective
biomarkers that could improve patient selection for AD clinical trials.
AclarusDx™ may be an important new tool to help identify clinical
populations who will potentially benefit most from novel and exciting
therapeutic advances.”
“With the availability of AclarusDx™, ExonHit will become one of the
first companies in the world to offer a blood diagnostic test devoted to
Alzheimer’s disease. The use of such assay, simple to perform, will be a
tremendous step forward compared to the current qualitative diagnostic
tests,” commented Loïc Maurel, M.D., President of the Management
Board of ExonHit Therapeutics. “We have a fully operational and GLP
compliant laboratory in our US facility capable of supporting AD studies
for the pharmaceutical industry.”
The patient population for the clinical validation study covered the
range of severe through mild AD to ensure the signature performed across
the continuum of the disease state where subjects presenting symptoms of
Alzheimer’s disease were having a MMSE (Mini-Mental State Examination)
score of less than 28. Over 200 individuals were assessed in the study.
From this total (110 patients with AD and 101 control subjects),
AclarusDxTM showed an overall accuracy of 71% identifying
patients with Azheimer’s Disease correctly in 74% of all cases. The
identification and removal of ambiguous samples (approximately 25%)
increased the accuracy of the test to 75%, and the number of correctly
identified AD patients to 80% (1). Scientific findings published
recently in Lancet Neurology indicate that over 30% of healthy
controls have profiles suggestive of AD based on analysis of their
cerebral spinal fluid, obtained by doing a lumbar puncture (2). The
results from the clinical validation study suggest that AclarusDx™, a
non-invasive blood based test, can be used within the battery of
cognitive instruments to help refine and classify the patient population
for clinical trials.
ExonHit will first introduce AclarusDx™ as a Research Use Only service
to pharmaceutical companies and leading academic centers conducting
clinical trials in Alzheimer’s disease. The clinical diagnostics market
will be served through working with partners, following CE marking in
Europe and In Vitro Diagnostic registration in the USA.
For EHT 0202, ExonHit’s lead therapeutic candidate in Alzheimer’s
disease, additional Phase IIa data will be presented later today also at
the CTAD (3). These results further support the initial findings
presented on September 14 at the 13th Congress of the
European Federation of Neurological Societies in Florence, Italy (4).
They confirm that EHT 0202 is safe and generally well tolerated in
patients and demonstrated an excellent compliance rate (>95%) for the
study. They also show that overall blood levels of EHT 0202 and its main
metabolites were stable during the study, suggesting that no change in
the molecule’s safety profile related to plasma levels is to be expected
during longer administration periods. Also, the positive efficacy trend
in the ApoE4 positive subpopulation was confirmed on different
assessment parameters. However due to the limited size and duration of
the study, no statistically significant changes were observed in the
other efficacy scales (NTB, CDR-SB, Zarit, NPI, CGI).
These first patient data support the advancement of EHT 0202 into Phase
IIb and ExonHit is in discussion with potential partners for further
development and commercialization of EHT 0202.
About AclarusDx™ (formerly EHT Dx21)
ExonHit Therapeutics has an extensively validated technical platform to
analyze transcript variations in a standardized, GLP compliant
environment with demonstrated reproducibility. This validated platform
has been used in a large clinical study to demonstrate its ability to
select AD patients through a simple blood sample and hence led to the
development of the AclarusDx™ Alzheimer product. The information
generated by the assay can be expanded and applied to clinical research
applications such as pharmagenomics.
About EHT 0202
EHT 0202 has a novel mechanism of action when compared to existing
Alzheimer’s disease therapeutics: it stimulates the α-secretase pathway,
thus enhancing the production of the procognitive and neuroprotective
sAPPα fragment of APP (Amyloid Precursor Protein). Since the stimulation
of the α-secretase pathway is to the detriment of Aβ amyloid peptide
production, EHT 0202 potentially reduces toxic Aβ plaque formation (5).
Phase I studies demonstrated good tolerability of EHT 0202 in both young
and aged healthy volunteers.
Preclinical studies have shown that EHT 0202 protects cortical neurons
against Aβ42-induced toxicity and that this neuroprotection is
associated with sAPPα induction. EHT 0202 has also demonstrated
procognitive properties in several animal models: age-related memory
impairment and scopolamine-induced amnesia (6).
About Alzheimer’s disease
Alzheimer’s disease is a progressive neurodegenerative condition that is
the most frequent cause of dementia in the aging population. An
estimated 26.6 million people worldwide had Alzheimer in 2006. This
number is anticipated to quadruple by 2050 to more than 100 million; 1
in 85 persons worldwide will be living with the disease (7). In France
alone, 800,000 people, or 18% of people above 75 years old, have
Alzheimer’s disease (8).
About ExonHit Therapeutics
ExonHit Therapeutics (Alternext: ALEHT) is a fast emerging healthcare
player active in both therapeutics and diagnostics. The Company is
applying its proprietary technology, based on the analysis of
alternative RNA splicing, to develop innovative molecular diagnostic
tests and therapeutics for neurodegenerative and cancer indications.
ExonHit has a balanced investment strategy with internal development
programs and strategic collaborations, in particular with bioMérieux and
Allergan.
ExonHit is headquartered in Paris, France and has U.S. offices in
Gaithersburg, Maryland. The Company is listed on Alternext of NYSE
Euronext Paris. For more information, please visit http://www.exonhit.com.
Disclaimer
This press release contains elements that are not historical facts
including, without limitation, certain statements on future expectations
and other forward-looking statements. Such statements are based on
management’s current views and assumptions and involve known and unknown
risks and uncertainties that could cause actual results, performance or
events to differ materially from those anticipated.
In addition, ExonHit Therapeutics, its shareholders, and its
affiliates, directors, officers, advisors and employees have not
verified the accuracy of, and make no representations or warranties in
relation to, statistical data or predictions contained in this press
release that were taken or derived from third party sources or industry
publications, and such statistical data and predictions are used in this
press release for information purposes only.
Finally, this press release may be drafted in the French and English
languages. In an event of differences between the texts, the French
language version shall prevail.
References
(1) Fehlbaum-Beurdeley P et al. Identification of patients with
Alzheimer’s disease using molecular signatures derived from splice
variant expression profiles from peripheral blood. Presented at the 2nd
Conference of Clinical Trials on Alzheimer’s Disease in Las Vegas, on
October 29, 2009.
(2) Visser P. et al. Alzheimer’s disease pathology in patients with
subjective cognitive impairment or mild cognitive impairment in the
DESCRIPA study: a prospective cohort study. Lancet Neurology 2009; 8:
619–27.
(3) Vellas B, Ousset PJ, Sol O, Desire L, Pando M. Safety and
exploratory efficacy of EHT 0202 in mild to moderate AD patients: a
3-month, randomized, double-blind, placebo-controlled, phase IIa study.
Presented at the 2nd Conference of Clinical Trials on
Alzheimer’s Disease in Las Vegas, on October 30, 2009.
(4) Vellas B et al. A 3-month, randomized, double-blind,
placebo-controlled, phase IIa study to assess safety and exploratory
efficacy of EHT 0202 as adjunctive therapy in mild to moderate AD
patients. Presented at the 13th Congress of the European
Federation of Neurological Societies; 12-15 September 2009 Florence,
Italy
(5) Marcade M, Bourdin J, Loiseau N, Peillon H, Rayer A, Drouin D,
Schweighoffer F, Desire L. Etazolate, a neuroprotective drug linking
GABAA receptor pharmacology to amyloid precursor protein processing.
Journal of Neurochemistry. 2008; 106: 392-404
(6) Pando M, Marcade M, Peillon H, Rayer A, Drouin D, Desire L. An
alpha-secretase stimulator drug for cognitive disorders associated with
neurodegeneration. Presented at the 12th congress of the
European Federation of Neurological Societies; 23-26 August, 2008;
Madrid, Spain
(7) Brookmeyer R, Johnson E, Ziegler-Graham K, MH Arrighi (July 2007). "Forecasting
the global burden of Alzheimer’s disease". Alzheimer's and Dementia
3 (3): 186–91
(8) Plan Maladie d’Alzheimer 2004-2007- Ministère des solidarités, de la
santé et de la famille
ExonHit Therapeutics
Media Contact
Corinne Hoff,
+33 1 58 05 47 04
corinne.hoff@exonhit.com
or
ALIZE
RP
Caroline Carmagnol, + 33 6 64 18 99 59
caroline@alizerp.com
or
Investor
Contact
Loïc Maurel, +33 1 53 94 77 00
loic.maurel@exonhit.com
