Acucela Receives Orphan Drug Designation from the FDA for the Treatment of Stargardt Disease

SEATTLE–(BUSINESS WIRE)–Acucela Inc. (“Acucela”), a clinical-stage ophthalmology company and
wholly-owned subsidiary of Kubota Pharmaceutical Holdings Co., Ltd.
(Tokyo 4596) that specializes in identifying and developing novel
therapeutics to treat and slow the progression of sight-threatening
ophthalmic diseases, announced today that the FDA (U.S. Food and Drug
Administration) granted orphan drug designation to Acucela’s leading
drug candidate emixustat hydrochloride (“emixustat”) for the treatment
of Stargardt disease. The orphan drug designation does not apply to
other indications emixustat is being developed.

The Orphan Drug Act (ODA) provides for granting special status to drugs
and biologics intended for the safe and effective treatment, diagnosis
or prevention of rare diseases and disorders that affect fewer than
200,000 people in the U.S.

Stargardt Disease

Stargardt disease, or fundus flavimaculatus, is a rare, genetically
inherited disease that directly affects the retina of the eye, often
resulting in the slow progression of vision loss in children. It may
also be referred to as Stargardt macular dystrophy or juvenile macular
degeneration and affects approximately 1 in 10,000 individuals worldwide1.
The most common form of the disease is caused by a genetic mutation of
the ABCA4 gene leading to the accumulation of toxic vitamin A byproducts
(primarily A2E) in the retina, which results in the gradual
deterioration of photoreceptors and vision. Symptoms of Stargardt
disease typically appear during childhood or adolescence, but in some
cases difficulty with eyesight and vision loss may not be identified
until later in life.

Stargardt disease affects less than 40,000 patients in the U.S. where it
is recognized as an orphan disease, subject to the Orphan Drug Act.
Currently, there are no known therapies that exist to slow the advance
of the disease, and it is recognized as a serious unmet medical need by
the United States Foundation of Fighting Blindness and the National Eye

Emixustat Hydrochloride

The visual cycle is the process by which vitamin A is recycled in the
eye; vitamin A is crucial to the visual process. Emixustat modulates the
visual cycle by inhibiting a critical enzyme of this pathway, retinal
pigment epithelium protein 65 (RPE65). Slowing the visual cycle reduces
the availability of vitamin A derivatives (11-cis- and
all-trans-retinal) to form precursors of A2E and related compounds. In
animal models of Stargardt disease and retinal degeneration, emixustat
was found to stop and reverse the accumulation of A2E and to preserve
the integrity of the retina. Emixustat when delivered orally was found
to be generally well tolerated in human clinical studies with delayed
dark adaptation being the most common ocular adverse event. Acucela is
planning to explore emixustat’s potential to stop or slow the
progression of vision loss in patients diagnosed with Stargardt disease
in future clinical studies.

Dr. Ryo Kubota, MD, PhD, and Chairman, President and CEO of Acucela,
states, “We are very pleased to receive FDA’s orphan drug designation
for emixustat to treat Stargardt disease. We are actively advancing the
development of emixustat to address this unmet medical need.”

1 Kaplan J, Gerber S, Larget-Piet D et al. A gene for
Stargardt’s disease (fundus flavimaculatus) maps to the short arm of
chromosome 1. Nature Genetics 1993;5(3):308-311.

About Acucela Inc.

Acucela Inc. is a wholly-owned subsidiary of Kubota Pharmaceutical
Holdings Co., Ltd. (Tokyo 4596) committed to translating innovation into
a diverse portfolio of drugs and devices to preserve and restore vision
for millions of people worldwide. Acucela’s pipeline includes drug
candidates and therapeutics for the treatment of retinitis pigmentosa,
proliferative diabetic retinopathy, intermediate AMD, Diabetic macular
edema, Stargardt disease and cataracts.;

Cautionary Statements

Certain statements contained in this press release are forward-looking
statements within the meaning of Section 27A of the Securities Act of
1933 and Section 21E of the Securities Exchange Act of 1934 and the
Private Securities Litigation Reform Act of 1995. Any statements
contained in this press release that are not statements of historical
fact may be deemed to be forward-looking statements. These
forward-looking statements include statements regarding our expectations
related to our development plans and ability to successfully develop and
commercialize our product candidates and the potential efficacy, future
development plans and commercial potential of our product candidates.
These statements are based on current assumptions that involve risks,
uncertainties and other factors that could cause the actual results,
events or developments to differ materially from those expressed or
implied by such forward-looking statements. These risks and
uncertainties, many of which are beyond our control, include, but are
not limited to: our investigational product candidates may not
demonstrate the expected safety and efficacy; our pre-clinical
development efforts may not yield additional product candidates; any of
our or our collaborators’ product candidates may fail in development,
may not receive required regulatory approvals, or may be delayed to a
point where they are not commercially viable; our clinical trials could
be delayed; new developments in the intensely competitive ophthalmic
pharmaceutical market may require changes in our clinical trial plans or
limit the potential benefits of our investigational product candidates;
the impact of expanded product development and clinical activities on
operating expenses; adverse conditions in the general domestic and
global economic markets; as well as the other risks identified in our
filings with the Securities and Exchange Commission. These
forward-looking statements speak only as of the date hereof and we
assume no obligation to update these forward-looking statements, and
readers are cautioned not to place undue reliance on such
forward-looking statements. For a detailed discussion of the foregoing
risks and other risk factors, please refer to our filings with the
Securities and Exchange Commission, which are available on Kubota
Pharmaceutical Holdings (Acucela’s parent company) investor relations
website (
and on the SEC’s website (

“Acucela,” the Acucela logo and “Kubota” are registered trademarks or
trademarks of Acucela Inc. or Kubota Pharmaceutical Holdings in various


Acucela Inc.
Michael Hasegawa, +81-3-5789-5872
Director, Corporate Communications
John Gebhart, +1-206-805-3972
Chief Financial