A Phase 1/2, RU-101 Ophthalmic Solution in Patients With Severe Dry Eye

This is a Phase 1/2, first-in-human, multicenter, dose escalation, double-masked, placebo
controlled study consisting of two stages. In Stage I, 3 cohorts are planned to evaluate
escalating doses of RU 101 ophthalmic solution, instilled 6 times daily into each eye for 4
weeks (28 days). Each cohort will comprise 4 patients randomized 3:1 to RU-101 or placebo. A
masked safety data review will be performed prior to each dose escalation to determine if
any dose limiting toxicities (DLTs) occurred and to define the MTD or highest dose to be
used in Stage II. In Stage II, an expanded cohort will receive the dose defined in Stage I
(MTD or highest dose if MTD is not reached), instilled 6 times daily into each eye for 12
weeks (84 days). The expanded cohort will comprise approximately 96 patients randomized 1:1
to RU-101 or placebo, provided in a double-masked manner.

Inclusion Criteria:

1. Male or female patients aged 18 to 80 years.

2. Patients have had dry eye symptoms at least 4 months.

3. Patients have the following signs in the worst eye:

1. Corneal staining score with fluorescein staining ≥ 6/15 with at least one in the
central

2. Conjunctival staining score with Lissamine Green ≥ 2/18

4. Patients who had been receiving treatment with eye drops of artificial tears,
Restasis, or topical steroids but have had insufficient efficacy or have found these
products to be intolerable. If using Restasis or topical steroids, patients must
agree to a 30-day washout period prior to the first IP dose (Day 0).

5. Female patients of child bearing potential must agree to have a urine pregnancy test
performed at Screening (must be negative) and agree to use a medically acceptable
form of birth control (e.g., intrauterine device, birth control pill, patch or
subcutaneous implant, condoms, diaphragm, or abstinence) throughout the duration of
IP instillation. Women considered capable of becoming pregnant include all females
who have experienced menarche and who have not experienced menopause (as defined by
amenorrhea for > 12 consecutive months) or have not undergone successful surgical
sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).

Exclusion Criteria:

1. Presence of anterior eye diseases except dry eye.

2. Intraocular pressure ≥ 22 mmHg at Screening.

3. Use of any ophthalmic solutions (including over-the-counter [OTC] solutions), serum
eye drops, or contact lenses during the Treatment Phase. Artificial tears are allowed
during the Screening Phase but must not be used from the first dose (Day 0) through
the Treatment Phase.

4. Use of eye drops of Restasis or topical steroids within 30 days of the first dose
(Day 0).

5. Use of antihistamines, beta blockers, tricyclic antidepressants, or antidepressants
with anticholinergic side effects during the Treatment Phase.

6. Patients with previous corneal transplantation or laser-assisted in situ
keratomileusis (LASIK).

7. Presence of graft-versus-host disease (GVHD).

8. Patients who have had other ocular surgery within 3 months prior to the first dose.

9. Patients with punctal plugs or punctal cautery < 3 months prior to the first dose.

10. Patients with severe dry eye due to Stevens-Johnson disease or ocular cicatricial
pemphigoid.

11. History of allergy to human serum protein products and/or any history of allergy to
yeast.

12. History of allergies to recombinant products, ophthalmic solutions, any constituents
of RU 101, or any solutions planned for use in this study.

13. Any significant chronic illness that, in the opinion of the Principal Investigator
(PI), could interfere with the study parameters.

14. Use of any investigational product or device within 30 days prior to the Screening
Visit or during the study.

15. Known history of alcohol and/or drug abuse within the past 12 months, which in the
opinion of the PI could interfere with study compliance, outcome measures including
safety parameters, and/or the general medical condition of the patient.

16. Those unable in the opinion of the PI to comply fully with the study requirements.