RESULTS Patient demographics • A total of 600 patients ≥12 years old enrolled in the extension study; 311 and 289 were originally randomized to treatment with clascoterone and vehicle, respectively, in the Phase 3 studies – The safety population included 598 patients treated with clascoterone (original randomization: 311 clascoterone, 287 vehicle) – The PP population included 319 patients, of whom 119 (37.3%) were on-study for a total of 12 months ○ During the Phase 3 studies, 167 and 152 PP patients received clascoterone and vehicle, respectively ○ In the extension study, 124 PP patients also treated truncal acne, including 67 and 57 who received clascoterone and vehicle, respectively, during the Phase 3 studies – The majority of patients were female and White; mean ± standard deviation age in the ITT and PP populations was 19.3 ± 6.2 and 19.8 ± 6.6 years, respectively (Table 1) Table 1. Patient demographics, subgroup ≥12 years old Original treatment assignment Clascoterone Vehicle Overall Characteristic ITT n = 311 PP n = 167 ITT n = 289 PP n = 152 ITT N = 600 PP N = 319 Sex Male 118 (37.9) 70 (41.9) 109 (37.7) 55 (36.2) 227 (37.8) 125 (39.2) Female 193 (62.1) 97 (58.1) 180 (62.3) 97 (63.8) 373 (62.2) 194 (60.8) Race Caucasian 279 (89.7) 157 (94.0) 257 (88.9) 134 (88.2) 536 (89.3) 291 (91.2) Asian 5 (1.6) 2 (1.2) 8 (2.8) 5 (3.3) 13 (2.2) 7 (2.2) Black or African American 16 (5.1) 5 (3.0) 16 (5.5) 9 (5.9) 32 (5.3) 14 (4.4) Other 11 (3.5) 3 (1.8) 8 (2.8) 4 (2.6) 19 (3.2) 7 (2.2) Ethnicity Hispanic or Latino 26 (8.4) 9 (5.4) 15 (5.2) 7 (4.6) 41 (6.8) 16 (5.0) Not Hispanic or Latino 285 (91.6) 158 (94.6) 274 (94.8) 145 (95.4) 559 (93.2) 303 (95.0) Age, years Mean 19.3 19.7 19.3 19.9 19.3 19.8 Median 17.0 18 17.0 18.0 17.0 18.0 Standard deviation 5.77 6.13 6.68 7.04 6.22 6.57 Range 12–50 12–50 12–50 12–50 12–50 12–50 Patients are summarized overall and according to the original treatment they received in the Phase 3 pivotal studies. Data shown as n (%) unless otherwise specified. ITT, intention-to-treat; PP, per-protocol. Safety • Overall, 108/598 (18.1%) patients in the safety population experienced a total of 187 TEAEs, with similar frequencies in patients previously treated with clascoterone compared with vehicle in the Phase 3 studies (Table 2) – The majority of TEAEs reported were mild or moderate in severity, and most were not considered related to clascoterone treatment – The most frequent TEAEs by percentage of patients affected were nasopharyngitis (2.8%) and upper respiratory tract infection (1.8%; Table 3) Table 2. Summary of TEAEs in patients ≥12 years old Original treatment assignment Category Clascoterone Vehicle Overall n = 311 n = 287 N = 598 Subjects with any TEAE 56 (18.0) 52 (18.1) 108 (18.1) Mild 35 (11.3) 36 (12.5) 71 (11.9) Moderate 27 (8.7) 23 (8.0) 50 (8.4) Severe 4 (1.3) 3 (1.0) 7 (1.2) Any test article–related TEAE 11 (3.5) 2 (0.7) 13 (2.2) Any TEAE leading to discontinuation 9 (2.9) 0 9 (1.5) Any serious TEAE 3 (1.0) 3 (1.0) 6 (1.0) Any test article–related serious TEAE 0 0 0 Any serious TEAE leading to discontinuation 1 (0.3) 0 1 (0.2) Any TEAE leading to death 0 0 0 Number of TEAEs, N 102 85 187 Related to test article 16 2 18 Not related to test article 86 83 169 Mild 55 53 108 Moderate 40 29 69 Severe 7 3 10 Patients are summarized overall and according to the original treatment they received in the Phase 3 pivotal studies. Safety population. Data shown as n (%) unless otherwise specified. TEAE, treatment-emergent adverse event. Long-term safety and efficacy of 1% clascoterone cream in patients ≥12 years old with acne vulgaris Lawrence F Eichenfield1, Adelaide A Hebert2, Linda Stein Gold3, Martina Cartwright4, Luigi Moro5, Jenny Han6, Nicholas Squittieri7, Alessandro Mazzetti5 1University of California San Diego School of Medicine, La Jolla, CA, USA; Rady Children’s Hospital San Diego, San Diego, CA, USA; 2UTHealth McGovern Medical School, Houston, TX, USA; 3Henry Ford Medical Center, Detroit, MI, USA; 4Cassiopea Inc., San Diego, CA, USA; 5Cassiopea S.p.A., Lainate, Italy; 6Pharmapace Inc., San Diego, CA, USA; 7Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA INTRODUCTION • Clascoterone cream 1% is a topical androgen receptor inhibitor approved for the treatment of acne vulgaris in patients aged ≥12 years old1 • Clascoterone efficacy and safety were evaluated in two identical, vehicle-controlled, Phase 3 studies (CB-03-01/25 and CB-03-01/26) in patients aged ≥9 years old with moderate-to-severe facial acne vulgaris – Twice-daily treatment with clascoterone cream 1% for 12 weeks resulted in significantly higher treatment success rates and greater reduction in lesion counts compared with vehicle cream treatment2 – Clascoterone was well tolerated, with a safety profile similar to that of vehicle • Patients from the Phase 3 studies could enter an optional long-term, open-label extension study; the safety results in patients ≥9 years old are published3 OBJECTIVE • To evaluate the long-term safety and efficacy of twice-daily 1% clascoterone cream in the subgroup of patients aged ≥12 years old who entered the long-term extension study METHODS Study design and patients • A multicenter, open-label, long-term extension study (CB-03-01/27) enrolled patients who completed 1 of the 12-week Phase 3 clinical trials (CB-03-01/25 and CB-03-01/26) • Male or nonpregnant female patients who completed 1 of the 12-week Phase 3 pivotal clinical trials (CB-03-01/25 and CB-03-01/26) and enrolled within 3 days of the final pivotal trial visit were eligible – Patients with any skin pathology or condition that could interfere with the study or who planned to use other topical or systemic antiacne preparations or undergo procedures on the face (or trunk, if applicable) were excluded – This analysis includes only patients aged ≥12 years old who entered the long-term extension study Treatment administered • Patients applied 1% clascoterone cream twice daily to the entire face and, if designated by the investigator and desired by the patient, to truncal acne, for 9 additional months of treatment – Total time applying clascoterone cream, including the Phase 3 studies, could be up to 12 months for patients originally randomized to clascoterone treatment – Clascoterone treatment could be discontinued if the Investigator’s Global Assessment (IGA) score was 0 or 1 (clear/almost clear) and reinstated if/when acne worsened Assessments • Safety was evaluated from frequencies of treatment-emergent adverse events (TEAEs), serious adverse events, and local skin reactions (LSRs), including telangiectasia, skin atrophy, striae rubrae, erythema, edema, scaling/dryness, stinging/ burning, and pruritus – Summarized in patients ≥12 years old who received at least one application of clascoterone (safety population) • Efficacy was evaluated from the IGA severity score for each treatment area, as applicable – Assessed at every in-clinic study visit (baseline and Months 1, 3, 6, and 9) using a 5-point IGA scale (0, clear; 4, severe) – Summarized in patients ≥12 years old who completed the study without significant protocol violations (per-protocol [PP] population) Statistical analysis • For demographic, efficacy, and safety data, continuous variables were described by descriptive statistics, and categorical data by frequency counts and percentage of patients within each category – Patient demographics are reported in the subgroup of patients ≥12 years old in the intention-to-treat (ITT) population • Missing data were not imputed Table 3. Most frequent TEAEs in patients ≥12 years old Original treatment assignment Category Clascoterone Vehicle Overall n = 311 n = 287 N = 598 Most frequent TEAEs Events, n Patients Events, n Patients Events, n Patients Application site acne 4 4 (1.3) 0 0 4 4 (0.7) Nasopharyngitis 7 6 (1.9) 14 11 (3.8) 21 17 (2.8) Respiratory tract infection, viral 1 1 (0.3) 4 4 (1.4) 5 5 (0.8) Sinusitis 3 3 (1.0) 2 2 (0.7) 5 5 (0.8) Upper respiratory tract infection 9 8 (2.6) 3 3 (1.0) 12 11 (1.8) Patients are summarized overall and according to the original treatment they received in the Phase 3 pivotal studies. Safety population. Data shown as n (%) unless otherwise specified. TEAE, treatment-emergent adverse event. • The frequency of LSRs on the face and trunk was low; frequencies were similar in patients previously treated with clascoterone compared with vehicle in the Phase 3 studies – The most common new or worsening LSRs in patients previously treated with clascoterone/vehicle were scaling/dryness (face, 10.0%/7.3%; trunk, 3.5%/4.5%) and erythema (face, 8.0%/7.7%; trunk, 6.1%/7.3%; Table 4) • No deaths were reported during the study Table 4. New or worsening LSRs on the face and trunk in patients ≥12 years old Original treatment assignment Symptom Clascoterone n = 311 Vehicle n = 287 Face Trunk Face Trunk Edema 5 (1.6) 1 (0.3) 5 (1.7) 5 (1.7) Erythema 25 (8.0) 19 (6.1) 22 (7.7) 21 (7.3) Pruritus 13 (4.2) 5 (1.6) 16 (5.6) 4 (1.4) Scaling/dryness 31 (10.0) 11 (3.5) 21 (7.3) 13 (4.5) Skin atrophy 3 (1.0) 1 (0.3) 4 (1.4) 4 (1.4) Stinging/burning 11 (3.5) 1 (0.3) 8 (2.8) 2 (0.7) Striae rubrae 1 (0.3) 2 (0.6) 2 (0.7) 1 (0.3) Telangiectasia 3 (1.0) 1 (0.3) 4 (1.4) 1 (0.3) Patients are summarized according to the original treatment they received in the Phase 3 pivotal studies. Safety population. Data shown as n (%) unless otherwise specified. LSR, local skin reaction. Efficacy • Among patients who completed the study without major protocol violations, the proportion with clear or almost-clear facial acne (IGA score 0/1) increased over time during treatment with 1% clascoterone cream, with almost half of patients (48.9%) overall having a facial IGA score of 0/1 at the end of the study (9 months; Figure 1) – Similar proportions of patients who originally received 1% clascoterone cream or vehicle in the Phase 3 studies were clear or almost clear at the end of the study Figure 1. Percentage of patients ≥12 years old with facial IGA 0/1 by visit Baseline 1 month 3 months 6 months 9 months 0 20 40 60 80 100 % p at ie nt s Clascoterone-to-clascoterone (n = 167) Vehicle-to-clascoterone (n = 152) Total (N = 319) 18.0 8.6 13.5 10.2 11.8 11.0 13.8 13.8 13.8 32.3 25.0 28.8 50.3 47.4 48.9 Patients are summarized overall and according to the original treatment they received in the Phase 3 pivotal studies. Per-protocol population. Data shown as % unless otherwise specified. IGA, Investigator’s Global Assessment. • The overall proportion of PP patients with clear or almost-clear truncal acne increased over time during 1% clascoterone cream treatment (Figure 2) – At the end of the study, the proportion of patients with a truncal IGA score of 0/1 was higher among those originally assigned to treatment with 1% clascoterone cream vs vehicle (61.2% vs 42.1%, respectively) Figure 2. Percentage of patients ≥12 years old with truncal IGA 0/1 by visit Baseline 1 month 3 months 6 months 9 months 0 20 40 60 80 100 3.0 5.3 4.0 23.9 14.0 19.4 34.3 26.3 30.6 44.8 45.6 45.2 61.2 42.1 52.4 % p at ie nt s Clascoterone-to-clascoterone (n = 67) Vehicle-to-clascoterone (n = 57) Total (N = 124) Patients are summarized overall and according to the original treatment they received in the Phase 3 pivotal studies. Per-protocol population. Data shown as % unless otherwise specified. IGA, Investigator’s Global Assessment. • Consistent with IGA results at each study visit, the overall proportions of PP patients who were clear or almost clear on the face increased with time on 1% clascoterone treatment, with the greatest proportion of patients who were clear or almost clear observed in patients applying clascoterone for 12 months (67/119 [56.3%]) CONCLUSION • Clascoterone cream 1% applied twice daily was well tolerated, and frequencies of TEAEs and LSRs were low throughout the study – Most reported TEAEs were mild in severity, and there was no accumulation of adverse events observed over time – No patient deaths were reported • Among patients who completed the study without major protocol violations, the proportion achieving clear or almost-clear skin on the face and trunk increased with duration of 1% clascoterone cream treatment and was highest for patients on-study for 12 months of treatment ACKNOWLEDGMENTS The studies were funded by Cassiopea S.p.A. Medical writing and editorial support were provided by Dana Lengel, PhD, of AlphaBioCom, LLC, and funded by Sun Pharma. DISCLOSURES LFE, AAH, and LSG were study investigators. LFE, AAH, and LSG were also compensated advisors to Cassiopea. AAH is an employee of the McGovern Medical School of The University of Texas Health Science Center at Houston, which received compensation from Cassiopea S.p.A. for study participation; she also received an honorarium for serving on the Cassiopea advisory board; all research grant funds were paid to her institution. LFE is an employee of the University of California San Diego, which received compensation from Cassiopea S.p.A. for study participation; he has also served as an investigator, advisor, or consultant for Almirall, Dermata, Galderma Laboratories, and Ortho Dermatologics. LSG is an employee of the Henry Ford Health System in Detroit, Michigan, which received compensation from Cassiopea S.p.A. for study participation; she also received personal fees for advisory, speaking, consulting, research, and/or other services with Almirall, Foamix, Galderma Laboratories, Novartis, Sol-Gel, and Sun Pharma. MC is employed as the vice president of medical affairs at Novan Inc.; was employed as the senior director of medical affairs at Cassiopea, Inc. at the time of the study; received personal fees as a consultant from Cassiopea S.p.A.; and receives personal fees as an adjunct faculty member from the University of Arizona. LM is an employee of Cassiopea S.p.A. and holds stock options in the company. JH is an employee of Pharmapace Inc. NS is an employee of Sun Pharmaceutical Industries, Inc. AM is employed as the chief medical officer for Cassiopea S.p.A. and holds stock options in the company; is a board member of Cassiopea S.p.A.; and served as the chief medical officer of Cosmo Pharmaceuticals. REFERENCES 1. WINLEVI® (clascoterone cream 1%) [package insert]. Sun Pharmaceutical Industries, Inc.; 2020. 2. Hebert A, et al. JAMA Dermatol. 2020;156(6):621–630. 3. Eichenfield L, et al. J Am Acad Dermatol. 2020;83(2):477–485.