Introduction • Rosacea is a chronic, inflammatory, facial skin condition affecting approximately 16 million people in the United States1,2 • Topical therapies such as metronidazole and azelaic acid are considered first- line options for the treatment of papulopustular rosacea2-5 • Oral tetracyclines, doxycycline and minocycline, are mainstays of treatment; however, they are associated with significant systemic side effects2,4 • FMX103 1.5% is a topical minocycline foam that was developed for the treatment of moderate-to-severe papulopustular rosacea. Efficacy and safety have been established in: – A Phase 2 clinical trial – 2 pivotal, identical, Phase 3, double-blind, vehicle-controlled studies (Study FX2016-11 and Study FX2016-12) • A Phase 1 open-label study (FX2017-14) was conducted to evaluate minocycline’s pharmacokinetic (PK) and safety profile following multiple-dose topical administration of FMX103 1.5% minocycline foam for moderate-to- severe facial papulopustular rosacea – Single-center, nonrandomized trial – 14 days, maximum-use conditions • This report presents data from the completed PK and safety study Methods • FX2017-14, a Phase 1, single-center, nonrandomized, single-period, PK and safety evaluation study of FMX103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea (Figure 1) – FMX103 1.5% foam applied daily to full face for 14 days – 20 subjects – Approximately 2 grams of FMX103 1.5% Figure 1. Study design Methods ➢ FX2017-14, a Phase 1, single-center, nonrandomized, single-period, PK and safety evaluation study of FMX103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea (Figure 1) ➢ FMX103 1.5% foam applied daily to full face for 14 days ➢ 20 subjects ➢ Approximately 2 grams of FMX103 1.5% Figure 1. Study design 3 FX2017-14 FMX103 1.5% (N=20) Baseline Day 1 Day 6 Day 9 Day 11 Day 12 Day 14 (End of Treatment) Inclusion Criteria ➢ Males and nonpregnant females ≥18 years ➢ Moderate-to-severe facial papulopustular rosacea (IGA score of 3 or 4) ➢ Presence or history of facial erythema or flushing Pharmacokinetic Evaluation ➢ PK blood samples: Pre-dose at 30 minutes prior to administration on Day 1, 6, 9, 11, 12, and 14; and post-dose at 2, 4, 8, 12, 16, and 24 hours after administration of study drug Safety Evaluation ➢ TEAEs, clinical laboratory tests, vital signs, physical examinations, clinical laboratory tests, and IGA scores IGA=Investigator’s Global Assessment; TEAE=treatment-emergent adverse event.IGA=Investigator’s Global Assessment; TEAE=treatment-emergent adverse event. Results • 20 subjects enrolled in the study • Baseline demographics and disease characteristics are shown in Table 1 Table 1. Baseline demographics and disease characteristics FMX103 1.5% (N=20) Mean age, years 47.3 Male, n (%) Female, n (%) 6 (30.0) 14 (70.0) Race, n (%) White 20 (100) IGA score, n (%) 3 – Moderate 4 – Severe 18 (90.0) 2 (10.0) Table 2. Summary of PK parameters FMX103 1.5% (N=19)* PK Parameter Day 1 Mean (SD) Day 14 Mean (SD) C max (ng,mL) 1.30 (0.92) 0.75 (0.54) T max (h) 11.8 (4.07) 9.5 (3.82) AUC 0-tldc (ng*h/mL) 21.3 (16.2) 23.1 (34.1) C 24 (ng/mL) 0.86 (0.64) 0.57 (0.42) AUC 0-tau (ng*h/mL) 22.5 (16.2) 15.8 (11.4) R ACC NA 0.77 (0.34) *1 subject had all plasma concentrations below the limit of quantification. AUC0-tau = area under the concentration-time curve from time zero (predose) through 24 hours; AUC0 -tldc = area under the concentration-time curve from time zero (pre-dose) to the time of last determinable concentration; C24 = plasma minocycline concentration 24 hours after FMX103 1.5% application; Cmax = maximum observed plasma concentration; RACC = accumulation ratio; SD = standard deviation; Tmax = time to maximum measured plasma concentration. Table 3. Study drug concentrations by time points in PK population, day 1 to day 14 Visit Time Point FMX103 1.5% (N=20) Mean (SD) Day 1 Pre-dose 2 hours post-dose 4 hours post-dose 8 hours post-dose 12 hours post-dose 16 hours post-dose 0.05 (0.20) 0.24 (0.36) 0.70 (0.75) 1.09 (0.89) 1.13 (0.96) 0.98 (0.77) Day 2 24 hours post-dose 0.78 (0.66) Day 6 Pre-dose 0.38 (0.40) Day 9 Pre-dose 0.37 (0.38) Day 11 Pre-dose 0.44 (0.37) Day 12 Pre-dose 0.40 (0.33) Day 14 Pre-dose 2 hours post-dose 4 hours post-dose 8 hours post-dose 12 hours post-dose 16 hours post-dose 0.34 (0.37) 0.40 (0.45) 0.53 (0.51) 0.62 (0.53) 0.61 (0.60) 0.56 (0.51) Table 4. Study drug concentrations by time points in PK population, 24 to 96 hours after final treatment with FMX103 1.5% Visit Time Point FMX103 1.5% (N=20) Mean (SD) Day 15 24 hours post-dose 0.45 (0.44) Day 16 48 hours post-dose 0.16 (0.35) Day 17 72 hours post-dose 0.09 (0.27) Day 18 96 hours post-dose 0.07 (0.32) Figure 2. Linear plot of mean plasma minocycline concentration, day 1 and day 14 following application of FMX103 1.5% Figure 2. Linear plot of mean plasma minocycline concentration, day 1 and day 14 following application of FMX103 1.5% Results (cont.) 8 LLOQ=lower limit of quantification. P la sm a M in oc yc lin e C on ce nt ra tio n (n g/ m L) ± S D 2.4 2.0 1.6 1.2 0.8 0.4 0.0 -0.4 Day 1 Day 14 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 0 2 4 8 12 16 24 48 Hours Post-Administration Day 1 Day 14 LLOQ 20 72 20 96 LLOQ=lower limit of quantification. Figure 3. Linear plot of mean plasma trough concentrations of minocycline 0.20 Figure 3. Linear plot of mean plasma trough concentrations of minocycline Results (cont.) 9 1 6 9 11 12 14 pre- dose 14 post- dose Tr ou gh P la sm a C on ce nt ra tio n of M in oc yc lin e (n g/ m L) + /– S D Days 0.80 0.60 0.40 20 20 20 20 20 20 20 0 Pharmacokinetics Summary • After daily application of FMX103 1.5%, PK parameters of minocycline were generally similar for day 1 and day 14. Plasma concentrations of minocycline were low across the study (Table 2) • Day 1 and day 14 plasma concentrations demonstrated a PK profile consistent with the dosing of FMX103 1.5%. The mean (SD) values for the maximum observed plasma concentration (Cmax) were approximately 1.30 ng/mL on day 1 and 0.75 ng/mL on day 14 (Tables 2-4; Figure 2) • Trough levels were approximately 0.5 ng/mL overall, from 24 hours after the first dose through 24 hours after the day 14 dose; mean (SD) values ranged from 0.34 (0.37) ng/mL to 0.78 (0.66) ng/mL (Table 3; Figure 3) • Steady-state appeared to be achieved within 1 day Table 5. Summary of TEAEs in the all-treated population FMX103 1.5% (N=20) Subjects with any TEAE, n (%) Number of TEAEs 1 (5.0) 2a Subjects with any treatment-related TEAE, n (%) Number of treatment-related TEAEs 1 (5.0) 1b Subjects with any serious TEAE, n (%) Number of serious TEAEs 0 0 Subjects with any severe TEAE, n (%) Number of severe TEAEs 0 0 Subjects with any TEAE leading to discontinuation of study, n (%) Number of TEAEs leading to discontinuation 0 0 aArthralgia, headache. bHeadache. Table 6. TEAEs in the all-treated population FMX103 1.5% (N=20) One or more TEAEs, n (%) 1 (5.0) Adverse events, n (%) Arthralgia 1 (5.0) Headache 1 (5.0) Safety Summary • FMX103 1.5% was generally safe and well tolerated • All 20 subjects completed the study • There were no serious TEAEs, no severe TEAEs, and no TEAEs that resulted in the study drug being withdrawn or requiring a dose reduction (Table 5) • 1 subject reported 2 TEAEs: arthralgia, which was thought to be unrelated to the study drug, and a mild headache, considered possibly related to the study drug (Table 6) Conclusions • The results of the Phase 1 PK and safety evaluation study showed that FMX103 1.5% was safe and well tolerated by subjects with moderate-to- severe facial papulopustular rosacea • Once-daily topical application of approximately 2 grams of FMX103 1.5% for 14 days yielded low plasma concentrations of minocycline over time and a PK profile consistent with dosing • TEAEs were reported in 1 subject, but there were no serious or severe TEAEs, and no subjects discontinued or required dose reductions secondary to a TEAE References 1. Li WQ, Cho E, Khalili H, et al. Rosacea, use of tetracycline, and risk of incident inflammatory bowel disease in women. Clin Gastroenterol Hepatol. 2016;14(2):220-225. 2. Taieb A, Gold LS, Feldman SR, et al. Cost-effectiveness of ivermectin 1% cream in adults with papulopustular rosacea in the United States. J Manag Care Spec Pharm. 2016;22(6):654-665. 3. Rainer BM, Kang S, Chien AL. Rosacea: epidemiology, pathogenesis, and treatment. Dermato- Endocrinology. 2018;9(1). 4. Oge LK, Muncie HL, Phillips-Savoy AR. Rosacea: diagnosis and treatment. Am Acad Fam Physicians. 2015;92(3). 5. Schaller M, Schofer H, Homey B, et al. Rosacea management: update on general measures and topical treatment options. J German Soc Dermatol. 2016;14(suppl 6):17-27. Disclosures This study was funded by Foamix Pharmaceuticals, Inc. Terry Jones, MD, served as the principal investigator on the study. Iain Stuart, PhD, is an employee of Foamix Pharmaceuticals. Acknowledgment Editorial support was provided by Maryann Meleka, MD, from p-value communications. Pharmacokinetics of Minocycline Foam FMX103 in Subjects With Moderate-to-Severe Facial Papulopustular Rosacea Under Maximum-Use Conditions: Results of a Phase 1 Study Terry M. Jones, MD,1 Iain Stuart, PhD2 1J&S Studies, Inc., College Station, Texas, USA; 2Foamix Pharmaceuticals, Inc., Bridgewater, New Jersey, USA Poster presented at the Winter Clinical Dermatology Conference; January 18-23, 2019; Koloa, Hawaii.