PowerPoint Presentation Conclusions • In a subset of only adolescent subjects (9 to 17 years of age) treated with topical SB204 4% once-daily, there was a statistically significant reduction (p<0.05) in inflammatory, non-inflammatory and total lesion reductions with SB204 4% compared to vehicle • The percent change from baseline in the number of non-inflammatory lesions was -33.4% for SB204 and -24.2% for vehicle (p=0.0013) • The percent change from baseline in the number of inflammatory lesions was -43.4% for SB204 and - 36.4% for vehicle (p=0.0113) • The percent change from baseline in the number of total lesions was -37.4% for SB204 and -29.1% for vehicle (p<0.001) • Statistical significance was achieved for IGA assessment of 2-grade change from baseline • All doses of SB204 administered in the studies were well tolerated and the adverse event profile was similar in active and vehicle treated subjects Efficacy, Tolerability and Safety of SB204 Gel in Adolescents (9 to 17 Years of Age) With Acne Vulgaris Diane Thiboutot1, Andrea Zaenglein2, Adelaide Hebert3, Lawrence Eichenfield4 1Department of Dermatology, Penn State Hershey Medical Center, Hershey, PA, 2Department of Dermatology and Pediatrics, Penn State Hershey Medical Center, Hershey, PA, 3Department of Dermatology, The University of Texas Medical School, Houston, TX, 4Department of Dermatology, University of California, San Diego, CA • SB204, a nitric oxide-releasing topical drug candidate, is in development for the treatment of acne vulgaris • SB204 was previously evaluated in two replicate, multi-center, randomized, double-blinded, vehicle-controlled, parallel group trials with >2600 subjects with moderate-to-severe acne (NI-AC301 and NI-AC302) • Acne vulgaris is a common skin disease in adolescents • A post hoc analysis was conducted on a subset of 905 adolescents ranging from ages 9 to 17 years old • SB204 has potential immunomodulating and broad-spectrum antimicrobial activity Introduction Demographics Tolerability Results Representative Clinical Photos from SB204 4% Treatment Group Immunomodulatory Activity of Nitric Oxide in Acne Nitric oxide inhibits the NLRP3 inflammasome, decreasing the downstream release of IL-1β and IL-17, as well as, kills P. acnes McHale K. Effects of SB204 on LPS-Induced Cytokine Release in an Ex-Vivo Human Skin Model. Presented at 2017 Dermatology Summer Symposium of the Alabama Dermatology Society. Mishra B et al. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome–dependent processing of IL-1β. Nature Immunology. 2013;14:52-60. Niedbala W et al. Regulation of Type 17 Helper T-Cell Function by Nitric Oxide During Inflammation Proc Natl Acad Sci USA. 2011;108(22):9220-9225. Niedbala W et al. Nitric Oxide-Induced Regulatory T Cells Inhibit Th17 but Not Th1 Cell Differentiation and Function. J Immunol. 2013;191(1):164-170. Qin M et al. Nitric Oxide Releasing Nanoparticles Prevent Propionibacterium Acnes Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response. J Invest Dermatol. 2015;135(11):2723-2731. Randomized (N = 905; 9 to 17 years of age) 12 weeks SB204 4% gel once daily (n [pooled] = 439) Vehicle gel once daily (n [pooled] = 466) • SB204 4% gel (~900mg) or vehicle (~900mg) were applied once daily to the entire face • Efficacy endpoints assessed: • Absolute change in inflammatory, noninflammatory and total lesion counts from baseline to week 12 • Success on Investigator’s Global Assessment (IGA) at week 12 (IGA success was defined as a score of clear (0) or almost clear (1) and ≥2 grades less than baseline) Baseline Week 12 NI-AC301 and NI-AC302 SB204 4% (n, pooled = 439) Vehicle (n, pooled = 466) Gender, n Male 228 (52%) 255 (55%) Female 211 (48%) 211 (45%) Age, mean 14 14 Baseline, mean (SD) Inflammatory Lesion Count 28 (5.7) 28 (5.9) Non-Inflammatory Lesion Count 42 (13) 42 (13) Total Lesions 70 (15) 70 (16) Baseline IGA Scores “Moderate” or a score of 3 377 (86%) 401 (86%) “Severe” or a score of 4 62 (14%) 65 (14%) Disposition, n Completed 397 (90%) 421 (90%) Discontinued 42 (10%) 45 (10%) Study Overview Efficacy Results Treatment Emergent Adverse Events (TEAEs) *P-values are based on analysis of covariance, using LOCF imputation (ITT population) *P-values are based on analysis of covariance, using LOCF imputation (ITT population) NI-AC301/302 n overall incidence (%) # of AEs Dermatitis Dryness Erythema Exfoliation Pain SB204 4% 23 1 (0.23%) 3 (0.68%) 2 (0.46%) 1 (0.23%) 7 (1.59%) Vehicle 15 0 (0.0%) 1 (0.21%) 3 (0.64%) 2 (0.43%) 5 (1.07%) Pruritus Rash Reaction Swelling Malaise Pyrexia SB204 4% 3 (0.68%) 2 (0.46%) 1 (0.23%) 1 (0.23%) 1 (0.23%) 1 (0.23%) Vehicle 2 (0.43%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.21%) Investigator Global Assessment Scoring Grade Description 0 Clear: Clear skin with no inflammatory or non-inflammatory lesions 1 Almost clear: Rare non-inflammatory lesions with rare papules (papules may be resolving and hyperpigmented, though not pink-red) 2 Mild: Some non-inflammatory lesions with no more than a few inflammatory lesions 3 Moderate: Up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one nodulocystic lesion 4 Severe: Up to many non-inflammatory and inflammatory lesions, but no more than a few nodulocystic lesions Post-hoc analysis conducted by IQVIA