ACKNOWLEDGEMENTS Study funded by Sol-Gel Technologies Ltd.; poster support provided by Galderma Laboratories, L.P., Fort Worth, TX EPS.P-SGT5401-03 Drug Microencapsulation Background Benefits of Microencapsulation • Creates a silicon dioxide (silica) microcapsule shell between the BPO and the skin5 • Helps control the release rate of the drug to improve tolerability6 • Can preserve the advantages of BPO while minimizing limitations6 Encapsulation Process4 Silica is added in 5–100 repetitive cycles to build up a silica shell around the BPO 47.4 20.7 49.2 28.2 0 15 30 Pe rc en ta ge o f S ub je ct s Ac hi ev in g IG A Su cc es s (IT T) 45 60 E-BPO (n=243) 95% CI: 16.7%, 36.8% 95% CI: 10.7%, 31.3% Vehicle (n=118) E-BPO (n=250) Vehicle (n=122) Study 1 Study 2 M ea n In fla m m at or y Le si on C ou nt Ch an ge F ro m B as el in e E-BPO Cream 5% (n=243) P <.001 P <.001 P <.001 Vehicle (n=118) -20 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 Baseline Week 2 Week 4 Week 8 Week 12 -10.5 -5.5 -14.6 -8.7 -16.8 -10.6 -17.4 -9.5 P <.001 M ea n In fla m m at or y Le si on C ou nt Ch an ge F ro m B as el in e (IT T) E-BPO Cream 5% (n=243) P <.001 P <.001 Vehicle (n=118) E-BPO Cream 5% (n=250) Vehicle (n=122) Study 1 Study 2 -17.4 -9.5 -20.3 -13.3 -25 -20 -15 -10 -5 0 M ea n In fla m m at or y Le si on C ou nt Ch an ge F ro m B as el in e P <.001 P <.001 P <.001 P <.001 Baseline Week 2 Week 4 Week 8 Week 12 0 5 10 15 20 25 30 35 -13.0 -8.0 -16.7 -10.5 -20.0 -12.4 -20.3 -13.3 E-BPO Cream 5% (n=250) Vehicle (n=122) INTRODUCTION • Rosacea affects at least 10% of fair skinned individuals and not uncommon in Black, Asian, and Hispanic populations1,7,8 • Over 16 million people in the United States have rosacea2 • Triggers for rosacea are wide-ranging and can include skin care products, cold and/or hot weather, spicy foods, and emotional stress1 • Rosacea is characterized as an inflammatory disorder of the facial skin that primarily affects the cheeks, nose, chin, forehead, and eyes1 • Rosacea signs present as facial erythema, flushing, papules, pustules, phymas, and telangiectasias1,7 • The disease is frequently characterized by remissions and exacerbations1 CRITICAL EVALUATION OF BENZOYL PEROXIDE IN ROSACEA: OLD CHALLENGES AND NEW CLINICAL OPPORTUNITIES WITH ENCAPSULATED BENZOYL PEROXIDE James Q. Del Rosso, DO1; Neal D. Bhatia, MD2; Hilary Baldwin, MD3; Linda Stein Gold, MD4; Seemal R. Desai, MD5,6; Sam Brantman, PharmD7 1JDR Dermatology Research, Las Vegas, NV; 2Therapeutics Clinical Research, San Diego, CA; 3The Acne Treatment & Research Center, Brooklyn, NY, and Rutgers Robert Wood Johnson Medical Center, New Brunswick, NJ; 4Henry Ford Health Systems, Detroit, MI; 5Innovative Dermatology, Plano, TX; 6Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, TX; 7Galderma Laboratories, L.P., Fort Worth, TX METHODS Co-primary Endpoints • Proportion of subjects with the primary measure of success, “Clear” (0) or “Almost clear” (1), in the Investigator Global Assessment (IGA) relative to baseline at Week 12 - The IGA scale ranged from “Clear” (0) to “Severe” (4) and included the number of papules/pustules and erythema severity • Absolute mean change in inflammatory lesion counts from baseline to Week 12 Secondary Endpoints • Percentage change in inflammatory lesion count from baseline to Week 12 • Absolute change in inflammatory lesion count from baseline to Week 8 Study Design of the Two Pivotal Phase 3 Trials for E-BPO Cream, 5% (Figure 1) REFERENCES 1. Thiboutot D, Anderson R, Cook-Bolden F, et al. Standard management options for rosacea: The 2019 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. Jun 2020;82(6):1501-1510. 2. van Zuuren EJ. Rosacea. N Engl J Med. 2017 Nov 2;377(18):1754-1764. 3. Tan J, Steinhoff M, Bewley A, et al. [published correction appears in in J Dermatolog Treat. 2020;31(2):210]. J Dermatolog Treat. 2020;31(2):168-174. 4. Steinhoff M, et al. Beyond the visible: rosacea and psoriasis of the face. The BMJ Hosted Content 2020. Accessed April 2021. https://hosted.bmj.com/media/images/beyond-the-visible-rosacea-and- psoriasis-of-the-face.pdf. 5. Kolli SS, Pecone D, Pona A, et al. Topical Retinoids in Acne Vulgaris: A Systematic Review. Am J Clin Dermatol. 2019 Jun;20(3):345-365. 6. Rosacea now estimated to affect at least 16 million Americans. National Rosacea Society. Winter 2010. Accessed October 19, 2021. https://www.rosacea.org/rosacea-review/2010/winter/rosacea- now-estimated-to-affect-at-least-16-million-americans. 7. Del Rosso JQ, Tanghetti E, Webster G, et al. Update on the Management of Rosacea from the American Acne & Rosacea Society (AARS). J Clin Aesthet Dermatol. 2019 Jun;12(6):17-24. 8. Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: The 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018 Jan;78(1):148-155. 9. Erlich M, Arie T, Koifman N, et al. Structure elucidation of silica-based core-shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy. J Colloid Interface Sci. 2020 Nov 1;579:778-785. 10. Fireman S, Toledano O, Neimann K, et al. A look at emerging delivery systems for topical drug products. Dermatol Ther. 2011 Sep-Oct;24(5):477-88. SUMMARY • Both Phase 3 studies met the co-primary endpoints of IGA success “Clear” (0) or “Almost clear” (1) (P <.02) and a significant reduction in the absolute mean change in inflammatory lesion counts (P <.001) versus vehicle at 12 weeks • E-BPO cream, 5%, had a well-tolerated safety profile similar to vehicle in both studies • A reduction in mean inflammatory count was seen as early as Week 2 in both studies and was maintained for the entirety of each 12-week study RESULTS • A reduction in mean inflammatory count was seen as early as Week 2 in both studies and was maintained for the entirety of each 12-week study (Figure 4) • Most subjects experienced adverse reactions that were mild or moderate in severity (Table 3) • The serious adverse event reported in the treatment arm was determined by the investigators to not be related to study drug • TEAEs are combined from Study 1 and Study 2 Study 1 Study 2 Characteristic E-BPOn=243 Vehicle n=118 E-BPO n=250 Vehicle n=122 IGA: Moderate 210 (86.4%) 104 (88.1%) 227 (90.8%) 112 (91.8%) IGA: Severe 33 (13.6%) 14 (11.9%) 23 (9.2%) 10 (8.2%) Mean lesion count (SD) 25.7 (11.07) 26.3 (12.45) 29.8 (14.00) 27.5 (13.04) Median lesion count (range) 22.0 (15–69) 21.0 (15–70) 25.0 (15–70) 22.5 (15–70) Mean age (years) 52.8 52.4 49.5 51.5 Male 60 (24.7%) 35 (29.7%) 69 (27.6%) 35 (28.7%) Female 183 (75.3%) 83 (70.3%) 181 (72.4%) 87 (71.3%) Grade Description 0 – Clear Skin clear of inflammatory papules or pustules 1 – Almost Clear Very few small papules or pustules and very mild dull erythema are present 2 – Mild Few small papules or pustules and mild dull or light pink erythema are present 3 – Moderate Several to many small or larger papules or pustules and moderate light to bright red erythema are present 4 – Severe Numerous small and/or larger papules or pustules and severe erythema that is bright red to deep red are present E-BPO (n=488) Vehicle (n=234) Subjects reporting any TEAE 99 (20.3%) 39 (16.7%) Serious TEAE 1 (0.2%) 1 (0.4%) Discontinued study drug 11 (2.3%) 3 (1.3%) Discontinued study 9 (1.8%) 2 (0.9%) Related AEs occurring in >1% of subjects treated with E-BPO Application site pain 11 (2%) 2 (1%) Application site erythema 11 (2%) 2 (1%) Application site pruritis 6 (1%) 1 (<1%) Application site edema* 4 (1%) 0 (0%) *Application site edema includes application site swelling and application site edema. Table 3. Treatment-Emergent Adverse Events (Safety Population) Figure 1. Two Phase 3, Double-blind, Randomized, Vehicle-controlled Studies Figure 5. IGA Success With E-BPO — Study 1 Subject 101021 Figure 2. IGA Success at Week 12 Figure 4. Mean Inflammatory Lesion Count Change From Baseline Figure 3. Mean Inflammatory Lesion Count Change From Baseline to Week 12 E-BPO cream, 5% E-BPO cream, 5% (once daily) Vehicle cream (once daily) 12 weeks of treatment • Men and women ≥18 years of age • Clinical diagnosis of moderate to severe rosacea with a baseline Investigator Global Assessment score of 3 or 4 • ≥15 to ≤70 inflammatory lesions • ≤2 nodules Randomization QD, self-applied 54 total study sites Study 1 E-BPO: n=243 Vehicle: n=118 Study 2 E-BPO: n=250 Vehicle: n=122 Ke y in clu sio n cr ite ria Baseline 2 4 8 12 Weeks • In both studies, E-BPO cream, 5%, demonstrated statistically significant improvement in the co-primary endpoint of the number of subjects achieving “Clear” or “Almost clear” • In Study 1, 47.4% of subjects treated with E-BPO achieved IGA success at Week 12 versus 20.7% of subjects treated with vehicle. In Study 2, it was 49.2% versus 28.2% of subjects (Figure 2) • In both studies, E-BPO demonstrated a significant reduction in inflammatory lesion counts from baseline to Week 12 versus vehicle (Figure 3) Study 1 Study 2 Baseline IGA 3 3 3 1 Inflammatory lesions 20 23 12 7 IGA 4 4 4 3 Inflammatory lesions 68 25 33 21 Week 4 Week 8 Week 12 Co-primary Endpoint Least squares means, standard deviations, and treatment P value from an analysis of covariance with factors of treatment group, analysis center, and treatment by analysis center interaction and baseline lesion count as a covariate. Negative least squares means values represent decrease from baseline. 2:1 Table 1. Baseline Characteristics of Subjects Table 2. Investigator Global Assessment (IGA) Scale Abbreviations: E-BPO = encapsulated benzoyl peroxide; IGA = investigator global assessment; ITT = intent-to-treat; SD = standard deviation; TEAE = treatment-emergent adverse event Week 4 Week 8 Week 12 Figure 6. IGA Failure With E-BPO — Study 1 Subject 106017 Baseline