Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease

This is a multicenter, randomized, double-masked, parallel group, placebo-controlled study
evaluating the effects of ALK-001 administered daily by mouth in subjects with Stargardt
disease (ABCA4-related).

Stargardt disease is a rare genetic disorder that leads to damage to the retina and results
in legal blindness. The onset of symptoms usually occurs during one's teenage years, although
symptoms can appear in children as young as 4 years old. There is currently no treatment for
Stargardt.

Stargardt disease is caused by a defective ABCA4 gene, which affects the processing of
vitamin A in the eye and leads to the formation of toxic vitamin A aggregates (called
"vitamin A dimers") in the eye. Vitamin A dimers are thought to contribute to vision loss in
Stargardt disease. ALK-001 is a chemically-modified vitamin A designed as a replacement of
vitamin A. ALK-001 has been changed specifically to prevent the formation of toxic vitamin A
dimers in the eye, without altering the normal processing of vitamin A to enable vision.

Trial participants will be randomly assigned to receive ALK-001 (30 subjects) or placebo (20
subjects) for one year. After one year of treatment, half of the participants (10 subjects)
receiving placebo will be randomly crossed over to receive ALK-001 for the following 12
months, while the remaining 10 subjects will continue on the placebo. All subjects initially
receiving ALK-001 will remain on the same treatment for 12 months.

Follow-up visits will take place 4 and 8 weeks after the initiation of treatment to assess
safety and tolerability, then after 6, 9, 12, 15, 18, 21 and 24 months to assess the safety,
tolerability and effects of ALK-001 on the progression of Stargardt disease.

The study is double-masked so that neither the participants, the clinical staff, nor the
sponsor, are aware of the treatment allocation (ALK-001 or placebo). A Data Safety Monitoring
Board (DSMB) will review safety and efficacy data throughout the study.

Simplified Inclusion Criteria:

- Male or female between 12 and 60 years old (inclusive), with any visual acuity

- Has a clinical diagnosis of typical autosomal recessive Stargardt macular dystrophy
(STGD1)

- Has provided a genetic report indicating at least two ABCA4 disease-causing mutations.
When only one ABCA4 disease-causing mutation is reported, sponsor's permission will be
required.

- At least one eye (called the "primary study eye") must have at least one
well-demarcated area of significantly reduced autofluorescence as imaged by fundus
autofluorescence (FAF)

- Primary study eye must have clear ocular media and adequate pupillary dilation,
including no allergy to dilating eyedrops, to permit good quality retinal imaging

- Healthy as judged by investigator

- Able and willing to comply with study requirements, restrictions and instructions and
is likely to complete the 24-month study

- Has signed and dated the informed consent forms (or assent where appropriate) to
participate

- Female of childbearing potential has signed the informed consent about birth defects
or attestation on contraception requirements

Main Exclusion Criteria:

- Has taken disallowed items (supplement containing vitamin A or beta-carotene,
liver-based products, or prescription oral retinoid medications) over the past 30 days

- Is lactating, pregnant, or has a positive serum or urine pregnancy test at screening
or at randomization

- Has concurrent medical condition or history, which in the opinion of the investigator,
is likely to prevent compliance with the protocol and/or interfere with absorption of
ALK-001 or study procedures

- Has clinically significant abnormal laboratory result(s) at screening

- Has active or historical acute or chronic liver disorder

- Has active or historical ocular disorder in the primary study eye that, in the opinion
of the investigator, may confound assessment of the retina morphologically or
functionally (this could include for example cataract surgery within the past 6
months, choroidal neovascularization (CNV), glaucoma, recurring uveitis, diabetic
retinopathy, other retinal disease, etc.)

- Has had intraocular surgery or injections in the primary study eye within 90 days of
the screening visit

- Has a clinically significant abnormal electrocardiogram (ECG), or has a corrected QT
interval (QTc) that is 450 ms or greater