Download Scientific discovery and innovation are the inspiration on

VCM Technology
Backgrounder
4TH QUARTER 2013
Scientific discovery and innovation are the inspiration on
which Acucela was founded. The Company is developing
potential approaches for the treatment and management of
sight-threatening diseases for which we believe current
therapies are inadequate.
Visual Cycle Modulation (VCM) Technology
The visual cycle is the biological conversion of light
into an electrical signal in the retina (back of the
eye) which is perceived by the brain as vision.
During exposure to bright light, the visual cycle is
extremely active and may produce toxic by-products
that cannot be eliminated. Over time, accumulation
of these toxic by-products can compromise function
of the visual cycle and damage the retina. Visual
cycle modulation is designed to slow the visual cycle
and potentially reduce the accumulation of toxic
by-products and the extent of oxidative damage to
the retina.
The Company’s VCM-based product candidate,
emixustat hydrochloride, has demonstrated
dose-dependent modulation of the visual cycle,
is non-retinoid and has a generally favorable
systemic safety profile in early clinical trials.
Trials are ongoing, and no Acucela products are
approved for sale.
In addition, Acucela intends to develop its product
candidates for additional ophthalmic indications
such as diabetic retinopathy/diabetic macular
edema, Stargardt disease, retinopathy of prematurity
and retinitis pigmentosa. However, there are no
clinical studies currently underway for these
indications.
Age-related Macular Degeneration (AMD)
The Disease
Age-related macular degeneration (AMD) is an
ocular disease which compromises the retina and
can result in vision loss, even blindness. The disease
exists in two forms, dry (non-exudative) and wet
(exudative). The dry form is characterized by the
presence of lesions in the back of the eye which can
spread over time. The most advanced stage of dry
AMD is known as geographic atrophy (GA). Patients
with GA can experience a gradual loss of fine central
vision that is needed to see objects clearly and
to perform common daily tasks, such as reading
and driving. The wet form is characterized by the
presence of leaky blood vessels in the back of the eye
which deposit fluid and blood beneath the retina and
is associated with a rapid loss of vision. Advanced
AMD (GA and wet AMD) is the leading cause of vision
loss and blindness among persons age 50 years and
older in the United States.
VCM Technology
Backgrounder
Age-related Macular Degeneration (continued)
4TH QUARTER 2013
Dry AMD is the most common form of AMD,
representing approximately 90% of all cases.
Approximately 15% of those who suffer from
AMD develop intermediate or advanced dry AMD.
The risk of developing advanced dry (GA) or wet
AMD increases with age. Wet AMD is an advanced
According to MarketScope, an independent research
firm, the number of people affected by AMD in the
United States and worldwide was 11 million and 127
million, respectively, in 2012 and these numbers
are expected to be 13 million and 146 million,
respectively, in 2017.
but less common form of AMD, representing
approximately 10% of all cases.
The Progress
Emixustat Hydrochloride: Drug Development Path
The Science
Emixustat hydrochloride, Acucela’s VCM
investigational product candidate, has been shown
in pre-clinical models to specifically target and
modulate an enzyme known as RPE65 and reduce
the accumulation of toxic by-products in the back
of the eye. Acucela believes that the visual cycle
could be a target for pharmacologic intervention to
potentially slow or halt the progression of various
retinal diseases, including AMD, and is evaluating
emixustat hydrochloride in clinical trials.
2012
Clinical
development
Phase 2b/3
trial commences
179 total subjects
exposed to emixustat
1 phase 2a trial
completed (GA subjects)
5 phase 1 trials
completed
2009
First human trial
2008
Non-clinical
development
2007
IND
Toxicology
Proof-of-concept in
pre-clinical model
2005
Medical chemistry
Emixustat Hydrochloride:
Directed at Upstream Therpeutic Target
Emixustat hydrocloride is being analyzed to determine whether
it intervenes at an early stage to slow lesion progression and
preserve the health of retinal tissue.
Aging, Oxidative Stress, Light Damage, Genetic Factors
(Drusen, RPE de/hyperpigmention, lipofuscin and A2E)
RPE Dysfunction
Early
A Phase 2b/3 clinical trial of emixustat
hydrochloride in subjects with GA associated with
dry age-related macular degeneration was initiated
in early 2013. Clinical data available to date for
emixustat hydrochloride demonstrate a generally
favorable safety profile. Emixustat hydrochloride
has been generally well tolerated in all five
completed Phase 1 clinical studies and a Phase 2a
proof-of-concept clinical study.
2013
Chronic Inflammation
Damage/Death of BPE Cells
Inter.
Acucela’s emixustat hydrochloride is an
investigational VCM product candidate currently in
clinical development for the potential treatment of
geographic atrophy (GA) associated with dry AMD.
Late
Photoreceptor Cell Death
Geographic
Atrophy
Choroidal
Neovascularization (CNV)
Contacts
US Headquarters
1301 Second Ave., Suite 1900
Seattle, WA 98101-3805
Phone: 206.805.8300
Fax: 206.805.8301
www.acucela.com
Japan Office
Level 18 Yebisu Garden Place Tower
4-20-3 Ebisu Shibuya-ku
Tokyo 150-6018
Phone: +81.3.5789.5872
Fax: +81.3.5789.5874
www.acucela.jp
Business Development Inquiries
Keiko Mitsunobu
Executive Director Alliance Management
and Business Development
[email protected]
Media Inquiries
Francesca Nolan
Director Corporate Communications
[email protected]