ACKNOWLEDGEMENTS: Study funded by Sol-Gel Technologies Ltd.; poster support provided by Galderma Laboratories, L.P., Fort Worth, TX. EPS.P-SGT5407-01 Silica is added in 5–100 repetitive cycles to build up a silica shell around the BPO RESULTS Subjects • 547 adult subjects were enrolled in the 40-week extension of the two 12-week, double- blind, vehicle-controlled phase 3 trials (Table 1). • Subjects were ≥18 years old with an Investigator Global Assessment [IGA] of 3 or 4, ≥15 inflammatory lesions, and ≤2 nodules • The Safety population included 535 of the 547 enrolled subjects (97.8%). All analyses were performed using the Safety population • 363 subjects enrolled in the extension were previously treated with E-BPO and 184 were previously treated with vehicle during the phase 3 trials. • All subjects were assigned to treatment with E-BPO. Subjects were followed for up to 40 weeks in the extension (for a total of up to 52 weeks). Safety Summary of Treatment-Emergent Adverse Events • Most TEAEs were mild or moderate in severity and were not considered to be related to study treatment (Table 2). Summary: Tolerability, Safety Population, Baseline to Week 52 • E-BPO remained well-tolerated over the course of 52 weeks • For each of the cutaneous safety and tolerability parameters, the percentage of subjects with no signs/symptoms increased from week 4 to week 52 (range 60.8% to 90.6%) • Reports of severe cutaneous safety and/or tolerability evaluations included 2 subjects with dryness, 1 subject with itching, and 1 subject with burning/stinging at week 40 • There were no severe cutaneous safety evaluations at week 52 • Facial erythema generally improved during the study (n=535), with a total percentage increase for subjects with none and mild erythema at week 52 and a total percentage decrease for subject with moderate and severe erythema (Figure 3) ENCAPSULATED BENZOYL PEROXIDE (E-BPO): A NOVEL FORMULATION OF BPO FOR LONG-TERM MANAGEMENT OF ROSACEA Neal D. Bhatia MD1; Edward Lain MD2; Hilary Baldwin MD3,4; Sam Brantman PharmD5; James Q. Del Rosso DO6,7; Raja K. Sivamani MD8,9 1Therapeutics Clinical Research, San Diego, CA; 2Sanova Dermatology, Pflugerville, TX; 3The Acne Treatment & Research Center, Brooklyn, NY; 4Rutgers Robert Wood Johnson Medical Center, New Brunswick, NJ; 5Galderma Laboratories, L.P., Fort Worth, TX; 6JDR Research, Las Vegas, NV; 7Advanced Dermatology & Cutaneous Surgery, Maitland, FL; 8Integrative Skin Science and Research, Sacramento, CA; 9Pacific Skin Institute, Sacramento, CA INTRODUCTION Key Points • BPO is a potent oxidizing agent • The utility of BPO in rosacea has been limited due to limited data on efficacy and adverse skin tolerability • A new formulation incorporating microencapsulation technology is tolerable over long- term use BPO has had a complex history in rosacea • Limited data in previous studies, especially with monotherapy • Effective when used in combination with clindamycin or erythromycin1,2 • While proven effective, unencapsulated BPO causes local skin irritation, including stinging, burning, and itching after application3 • Demonstrated to be effective in killing Demodex folliculorum4 METHODS Study Objective: • Two 12-week phase 3 trials of microencapsulated benzoyl peroxide cream, 5% (E-BPO) previously demonstrated significant efficacy, rapid onset of action as early as week 2, and good safety and tolerability at week 12 • This 52-week study observed the nature, severity, and frequency of adverse events and the cutaneous safety and local tolerability of E-BPO when applied once daily (Figure 1) Safety endpoints: • The frequency of both local and systemic adverse events • Investigator cutaneous safety assessment (dryness and scaling) and local tolerability assessment (itching and burning/stinging) at baseline and all postbaseline study visits Termination: • The study was terminated early per protocol when a minimum number of patients were followed for a minimum time to adequately assess long-term safety as specified in the ICH E1A guidance. SUMMARY • The cutaneous safety and local tolerability assessments demonstrated that E-BPO, when applied once daily for up to 52 weeks, was generally safe and well-tolerated • The evaluations of IGA score and facial erythema showed improved clinical outcomes after 4 weeks and for up to 52 weeks of treatment with E-BPO E-BPO (n=535) Any TEAE 185 (34.6%) Any serious TEAE 10 (1.9%) Discontinued E-BPO because of a TEAE 5 (0.9%) Discontinued from the study because of a TEAE 4 (0.7%) Maximum severity of TEAE Severe 8 (1.5%) Moderate 81 (15.1%) Mild 96 (17.9%) Relationship to study drug Related 17 (3.2%) Not related 168 (31.4%) *Note: Treatment-emergent adverse events are those events with an onset after the first application of E-BPO Cream 5%. Related defined as “definitely,” “probably,” or “possible.” Not related defined as “unlikely” or “not related.” Study terminated by sponsor 146 (26.7%) Withdrawal by subject 48 (8.8%) Lost to follow-up 21 (3.8%) Adverse event 4 (0.7%) Protocol violation 2 (0.4%) Pregnancy 1 (0.2%) Physician decision 1 (0.2%) Other 1 (0.2%) Worsening of condition 0 Lack of efficacy 0 Figure 2. Study Design Figure 3. Erythema at Postbaseline Visits, Safety Population Figure 4. Kaplan–Meier Analysis of Time to First Retreatment Figure 1. Encapsulation Table 1. Baseline Demographic and Clinical Characteristics Table 2. Patient Adverse Event Summary Table 3. Summary of Subject Completion/Discontinuation Drug Microencapsulation Background Benefits of Microencapsulation • Creates a silicon dioxide (silica) microcapsule shell between the BPO and the skin • Helps control the release rate of the drug to improve tolerability • Can preserve the advantages of BPO while minimizing limitations REFERENCES 1. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris [published correction appears in J Am Acad Dermatol. 2020;82(6):1576]. J Am Acad Dermatol. 2016;74(5):945-973. [Table V pg. 951; p. 951 col1, p3; p951 col2p2.] 2. Brammann C, Müller-Goymann CC. Int J Pharm. 2020;578:119074. [pg2, col 2, para3; pg 7 Table 1; pg 9 col 1 para 1; pg 9 col 2 para 4; pg 6 col 1 para 5; pg 6 col 2 para 5] 3. Kolli S, Pecone D, Pona A, et al. Topical retinoids in acne vulgaris: a systematic review. Am J Clin Dermatol 2019;20(3):345-365. [pg 345 Abstract; pg 346 col 1, para 1; pg 362, col 2 para2; pg 362 col 1 para 3- col 2 para 1] 4. Oztürkcan S, Ermertcan AT, Sahin MT, Afşar FS. Efficiency of benzoyl peroxide-erythromycin gel in comparison with metronidazole gel in the treatment of acne rosacea. J Dermatol. 2004 Aug;31(8):610-7. doi: 10.1111/j.1346-8138. 5. 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. doi: 10.1016/j.jcis.2020.06.114. Abbreviations: E-BPO=encapsulated benzoyl peroxide; ICH=International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use; IGA=investigator global assessment; MedDRA=Medical Dictionary for Regulatory Activities; TEAE=treatment-emergent adverse event. Vehicle 12 Weeks 52 Weeks 547 enrolled in 54-07 • 363 previously treated with E-BPO in Study 1 and 2 • 184 previously treated with vehicle in Study 1 and 2 E-BPO Cream 5% Applied E-BPO daily for up to an additional 40 weeks • Subjects were on treatment only when IGA >1 Study 1 and 2 SGT 54-07 Pe rc en ta ge o f P at ie nt s (% ) None Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 Week 28 Week 32 Week 36 Week 40 Week 44 Week 48 Week 52 Mild Treatment Week Moderate Severe 0 25 50 75 100 Baseline = 0.4% Week 52 = 11% Baseline = 14.4% Week 52 = 0.5% Baseline = 9.7% Week 52 = 70.3% Baseline = 75.5% Week 52 = 18.2% Pe rc en t o f P at ie nt s W ith ou t R el ap se • Mean of 1.4 retreatments • Median number of treatment-free days was 58 For patients with a score of 0 at the beginning of the extension, the mean time to first retreatment was 125.1 days 0 10 20 30 40 50 60 70 80 90 100 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 280 290 Treatment-free Days Until First Retreatment 0 10 30 20 40 50 100 90 80 70 60 Censored A Multicenter, Open-label, Long-term Safety Study of E-BPO to Evaluate the Safety of E-BPO in Patients With Papulopustular Rosacea All Enrolled Subjects, N=547, 59% (N=323) completed the study, and 41% (N=224) did not complete. See Table 3. E-BPO Provided a Sustained Effect in Rosacea Patients for Over 1 Year (52 Weeks) Vehicle in Phase 3 Trials (n=172) E-BPO Cream, 5% in Phase 3 Trials (n=363) All Patients (n=535) Age (years) Mean (SD) 52.0 (12.75) 51.3 (13.88) 51.5 (13.52) Median 53 (22-81) 52.0 (19-81) 53.0 (19-81) Sex Male 52 (30.2%) 101 (27.8%) 153 (28.6%) Female 120 (69.8%) 262 (72.2%) 382 (71.4%) Inflammatory Lesion Count Mean (SD) 27.6 (12.83) 28.8 (13.24) 28.4 (13.11) Median 23.0 (15-70) 24.0 (15-70) 24.0 (15-70) IGA 3 - Moderate 157 (91.3%) 320 (88.2%) 477 (89.2%) 4- Severe 15 (8.7%) 43 (11.8%) 58 (10.8%) Censored = Subjects who discontinued the LTSS while not being treated and had not yet previously relapsed were considered censored in the Kaplan–Meier analysis.