CyclASol for the Treatment of Moderate to Severe Dry-eye Disease (DED)

This phase 2 study explored the safety, efficacy and tolerability of two CyclASol
concentrations as one drop twice daily versus vehicle (placebo). In addition to the masked
vehicle control arm, an open-label comparator arm consisting of Restasis was included.

The study explored a range of signs and symptoms of DED to gain an understanding of the
possible treatment effects in comparison to vehicle and estimation of effect sizes. In line
with current treatment guidelines, the proposed phase 2 population consisted of patients
suffering from moderate to severe DED.

The primary treatment comparisons in this study were between the two CyclASol concentrations
versus vehicle for the sign variable total corneal fluorescein staining and the symptom
variable dryness severity visual analogue scale at day 113. All other comparisons between
treatments groups were considered secondary analyses.

Inclusion Criteria:

- Signed Informed Consent Form and HIPAA (Health Insurance Portability and
Accountability Act ) document

- Patient-reported history of dry eye in both eyes

- Current use of over-the-counter and/or prescription eye drops for dry eye symptoms

- Ability and willingness to follow instructions, including participation in all study
assessments and visits

Exclusion Criteria:

- Women who are pregnant, nursing or planning a pregnancy

- Unwillingness to submit a blood pregnancy test at screening and at the last visit (or
early termination visit) if of childbearing potential, or unwillingness to use
acceptable means of birth control

- Clinically significant slit-lamp findings or abnormal lid anatomy at screening

- DED secondary to scarring or ocular or periocular malignancy

- History of herpetic keratitis

- Active ocular allergies or ocular allergies that are expected to be active during the
study period

- Ongoing ocular or systemic infection at screening or baseline

- Wear of contact lenses within 3 months prior to screening or anticipated use of
contact lenses during the study

- History of no response to previous topical Cyclosporine A and/or use of topical
Cyclosporine A within 6 months prior to screening

- Intra-ocular surgery or ocular laser surgery within the previous 6 months, or have any
planned ocular and/or lid surgeries over the study period

- Presence of an uncontrolled systemic disease

- Presence of a known allergy and/or sensitivity to the study drug or its components