New Acucela Data on the Effect of Emixustat Hydrochloride on Retinal Thickness in Diabetic Retinopathy

Acucela Inc. (“Acucela”), a clinical-stage ophthalmology company and
wholly-owned subsidiary of Kubota Pharmaceutical Holdings Co., Ltd.
(Tokyo 4596), announced today new data on the effect of emixustat
hydrochloride on retinal thickness in diabetic retinopathy (DR).

The study (Protocol 4429-203) is a randomized, placebo-controlled, phase
2 clinical trial exploring the effect of oral emixustat hydrochloride in
a proliferative diabetic retinopathy (PDR) population with and without
macular edema. Twenty-four subjects were enrolled in the study, in which
subjects in the emixustat group were titrated to their maximum tolerated
dose of up to 40 mg per day. Beyond the initial assessment of the
primary endpoint, a key secondary objective was to evaluate the effects
of emixustat on the change in central subfield (retinal) thickness as
assessed by spectral domain optical coherence tomography (SD-OCT) from
baseline to Day 85.

The study results indicate that the emixustat group experienced a
reduction in central subfield thickness when compared to placebo at a
statistical significant level (difference in means of 48.1 microns
favoring emixustat, p=0.0764; statistical significance pre-specified at
p<0.1). Additionally, the emixustat group experienced a reduction in
total macular volume in the study eye compared to placebo that also met
statistical significance (difference in means of 0.361 mm3
favoring emixustat, p=0.0263). Both pre-specified analyses included nine
patients in the emixustat group and eleven patients in the placebo group.

These results illustrate the potential for emixustat to decrease retinal
thickness in patients with DR. From these phase 2 findings, Acucela is
preparing to advance the clinical program and is actively discussing
research partnerships prior to the planned regulatory approval studies.

Dr. Ryo Kubota, MD, PhD, Chairman, President and CEO of Acucela stated,
“We are thrilled to see these results for emixustat in the diabetic
retinopathy population and are excited to advance the program. This
proof of concept is exciting as it not only addresses an important unmet
need but does so through oral administration, a first for the industry.
We are now focused on securing the right strategic partner as we
finalize our plans to advance our clinical program.”

About Diabetic Retinopathy and Diabetic Macular Edema

Nearly 415 million people in the world have diabetes(1),
a chronic condition that affects the function of insulin, a hormone that
regulates blood sugar. Diabetics are at an increased risk of developing
serious eye conditions, including diabetic retinopathy (DR). DR is a
very common complication of diabetes and a leading cause of vision loss
in adults. Loss of vision from DR is often characterized by blurred
central vision with some dark patches. DR is a progressive condition in
which there is damage to the tiny blood vessels, or capillaries, of the
retina; this vascular damage results in a chronic decrease in oxygen
supply to retinal cells.

DR is a progressive condition that can be broadly classified into:
non-proliferative and proliferative diabetic retinopathy (PDR),
depending on the progression of the disease. Diabetic macular edema
(DME) is a manifestation of non-proliferative diabetic retinopathy and
can develop at any stage of diabetic retinopathy. DME is caused by leaky
blood vessels in the retina that result in blurred vision, loss of
contrast, and overall vision loss, and is the most common cause of
vision loss in diabetic patients. PDR occurs when chronic retinal
hypoxia causes proliferation of new, fragile vessels that tend to leak
fluid and blood. This is the most advanced stage of diabetic eye disease
and can result in permanent vision loss. PDR affects over 19 million
people worldwide today, and this number is expected to grow to almost 22
million by 2020(2).

The most important risk factors for DR are increased blood sugar levels,
raised blood pressure, and longer duration of diabetes. All people with
Type 1 or Type 2 diabetes are at risk for DR and DME. The risk of
developing DR or DME increases significantly the longer a person has
diabetes. The American Academy of Ophthalmology estimates that nearly
80% of patients with Type 1 diabetes will have developed DR after living
with diabetes for 15 years. Early treatment of DR or DME can slow the
progression of the disease, but there are currently no treatments that
can reverse advanced vision loss.

(1) IDF Diabetes Atlas. 7th ed. Brussels:
International Diabetes Federation; 2015.(2)
Market Scope, The Global Retinal Pharmaceuticals & Biologic Market, 2015.

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 development pipeline include
drug candidates for the treatment of diabetic retinopathy, diabetic
macular edema, Stargardt disease, age-related macular degeneration,
cataracts and presbyopia, and, optogenetics-based gene therapy for the
treatment of retinitis pigmentosa. The company is also developing a
handheld OCT device for the monitoring of neovascular retinal diseases,
to be used directly by patients. http://www.acucela.com;

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 (http://www.kubotaholdings.co.jp/en/ir/)
and on the SEC’s website (http://www.sec.gov).

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

View source version on businesswire.com: https://www.businesswire.com/news/home/20180621005555/en/