Timothy L. Comstock, OD Oliver D. Schein, MD Tuyen Ong, MD Karen Kesler, PhD

1. Safety and Efficacy of Mapracorat Ophthalmic Suspension in the Treatment of Inflammation Following Cataract Surgery: Adaptive Design Study Timothy L. Comstock, OD Oliver D. Schein, MD Tuyen Ong, MD Karen Kesler, PhD Disclosures: T Comstock and T Ong are employees of Bausch & Lomb, Inc. O Schein is a consutlant for Bausch & Lomb, Inc. Karen Kesler is an employee of Rho, Inc. which conducted the statistical analysis.

2. Purpose To identify the most effective drug concentration and dose frequency of mapracorat (BOL-303242-X), a novel selective glucocorticoid receptor agonist (SEGRA), for the treatment of inflammation following uncomplicated cataract surgery.

3. Methods Phase II, multicenter, randomized, double-masked, parallel-group, vehicle-controlled, dose ranging study. Subjects were aged ≥18 years with postoperative anterior chamber (AC) cells of ≥Grade 2 (6-15 cells) on the day following uncomplicated cataract surgery. Subjects expecting to require concurrent ocular therapy with topical NSAIDs, mast cell stabilizers, antihistamines, or decongestants, or systemic NSAIDs or systemic/ocular corticosteroids were excluded.

4. Visit 3 [Post-op Day 1] • Clinical assessment of ocular symptoms • Eye examination (VA, IOP, biomicroscopy) • AEs & concomitant medications • Determination of eligibility • Visit 2 [Surgery] • AEs & concomitant medications • Visit 1 [Screening](≤14 days prior to surgery) • Eligibility assessment • Clinical assessment of ocular symptoms • Eye examination (VA, IOP, biomicroscopy, fundoscopy) • AEs & concomitant medications • Visit 6 [Day 15 ±1] • Clinical assessment of ocular symptoms • Eye examination (VA, IOP, biomicroscopy, fundoscopy) • AEs & concomitant medications • Visit 7 [Day 18 ±1] • Clinical assessment of ocular symptoms • Eye examination (VA, IOP, biomicroscopy) • AEs and concomitant medications • Visit 4 [Day 3 ±1] • Clinical assessment of ocular symptoms • Eye examination (VA, IOP, biomicroscopy) • AEs & concomitant medications • Visit 5 [Day 8 ±1] • Clinical assessment of ocular symptoms • Eye examination (VA, IOP, biomicroscopy) • AEs & concomitant medications Mapracorat Vehicle Methods Eligible subjects self-administered 1-2 drops of study treatment (mapracorat 1%, 2%, 3% or vehicle) QD, BID, or QID for 14 days and completed 7 visits.

5. Methods Primary efficacy endpoint: Proportion of subjects with complete resolution of AC cells at visit 5 (postoperative day 8) Secondary efficacy endpoints: Proportion of subjects with Grade 0 pain at visit 5 and at each visit Resolution of AC cells, AC flare and overall AC inflammation at each visit Safety endpoints: Incidence of ocular and non-ocular adverse events (AEs) Change from baseline in intraocular pressure (IOP), visual acuity (VA), and biomicroscopy and ophthalmoscopy findings

6. Results: Subjects 415 subjects were randomized and included in the ITT population Subjects ranged in age from 22 to 90 years with a mean (SD) age of 67.8 (10.4) years. The median ages and proportion of male and female subjects were similar for all treatment groups

7. Results: Complete Resolution of AC Cells at Visit 5 (postoperative day 8)—Primary Efficacy Endpoint • The mapracorat 2% QID and all 3% dose frequencies were highly significantly better than vehicle for resolution of AC cells (28.3%, 25.4%, 25.0% and 30.0%, respectively vs. 5% for vehicle). † † † † * * % Subjects with complete Resolution *P<0.05, †P<0.0005

8. Results: Grade 0 Pain at Visit 5 (postoperative day 8) • The mapracorat 2% QID and all 3% dose frequencies were significantly better than vehicle for pain resolution (78.3%, 71.2%, 75.0% and 70.0%, respectively vs. 50% for vehicle). * * * * % Subjects with Grade 0 Pain *P<0.05

9. Results: Adverse Events Serious Adverse Events (SAEs) No non-ocular SAEs 2 treatment-emergent ocular SAEs Cystoid macular edema (CME; 3% QD group, possibly related to the study group and probably related to study procedure) Subretinal neovascularization (3% BID group, unrelated to the study drug or study procedure) Treatment-Emergent and Related Non-Ocular AE’s 3 events total Rash (Vehicle group) Headache (2% QID group) Nausea –(3% QD group)

10. Results: Adverse Events

11. Results: Mean IOP for Each Visit, Safety Population • Mean IOP did not change from baseline for any treatment. • Four reports of increased IOP ≥10 mm Hg (1 vehicle, 2 mapracorat 1% BID, 1 mapracorat 3% BID) were not dose related and none exceeded 30 mm Hg. Mean IOP (mmHg)

12. Conclusions Mapracorat 2% QID treatment and all 3% dose frequencies (QD, BID, QID) demonstrated statistically significant improvements in both AC cells and Grade 0 pain at visit 5 (postoperative day 8) compared with vehicle. Results for secondary endpoints, including results at visit 6 (day 15) and visit 7 (day 18), were consistent with primary outcomes (data not shown) Treatment related adverse effects were infrequent in all treatment groups IOP effects were similar to vehicle.