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Acucela Initiates Phase 2a Study of Emixustat Hydrochloride Addressing Patients with Stargardt Disease

Posted in Technology & Research

SEATTLE (January 26, 2017) — Acucela Inc. (“Acucela”), a clinical-stage ophthalmology company and 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, announced today that on January 25, 2017, the first patient
has enrolled in a study to evaluate Acucela’s leading drug candidate, emixustat hydrochloride (“emixustat”) in subjects with macular
atrophy secondary to Stargardt disease.

This multicenter, randomized, masked phase 2a study is designed to evaluate the pharmacodynamics, safety and tolerability of
emixustat in subjects with macular atrophy secondary to Stargardt disease. Approximately 30 subjects will be enrolled at 4 to 6
clinical sites in the United States. Subjects will be randomly assigned to one of three treatment arms in a 1:1:1 ratio. Treatment arms
include: emixustat 2.5 mg, emixustat 5 mg, and emixustat 10 mg. Subjects will orally take study drug once daily in the evening for
one month.

“This is an important therapeutic development for patients with Stargardt Disease,” said Dr. Hendrik Scholl from the University
Hospital in Basel Switzerland and Study Director of the Stargardt Disease Natural History Study (PROGSTAR) sponsored by the
Foundation Fighting Blindness (FFB). “Emixustat addresses a well-understood mechanism that leads to toxic accumulation of material
underneath the retina linked to visual loss in Stargardt disease and therefore is a promising compound for this debilitating disease.”
Additionally, Dr. Ryo Kubota, MD, PhD, and Chairman, President and CEO of Acucela stated that “Stargardt disease represents a
serious sight threatening unmet medical need, and we are pleased to start our Phase 2a study of emixustat in subjects with Stargardt

“We applaud Acucela’s evaluation of emixustat for people with Stargardt disease, a devastating form of inherited macular
degeneration, which causes significant central vision loss in young people, and for which there are currently no therapies,” said
Patricia Zilliox, Ph.D., chief drug development officer, FFB-CRI. “Preserving vision by slowing degeneration would be a major
benefit for those affected.”

The FDA (U.S. Food and Drug Administration) granted orphan drug designation to emixustat for the treatment of Stargardt disease.
(See January 5, 2017 press release titled “Acucela Receives Orphan Drug Designation from the FDA for the Treatment of Stargardt

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 Institute.

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.

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.;

About Foundation Fighting Blindness

The Foundation Fighting Blindness was established in 1971. It has since raised more than $700 million for research aimed at
preventing, treating and curing blindness caused by retinal degenerative diseases. In excess of 10 million Americans, and millions
more worldwide, experience vision loss due to retinal degeneration. Through its support of focused and innovative science, the
Foundation drives the research that has and will continue to provide treatments and cures for people affected by retinitis pigmentosa,
macular degeneration, Usher syndrome and other inherited retinal diseases.

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 jurisdictions.


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