PowerPoint Presentation PRESENTED AT THE WINTER CLINICAL DERMATOLOGY CONFERENCE - HAWAII® (WCH23), JANUARY 13–18, 2023, KOHALA COAST, HI, USA CONCLUSIONS • Once-daily, nonsteroidal roflumilast foam 0.3% provided improvement across multiple efficacy endpoints versus vehicle in patients with SD in a phase 3 trial – 80% of patients achieved IGA Success and >50% achieved complete clearance by Week 8 – >60% of patients achieved an itch response at Week 8, with significant improvements at the 2- and 4-week assessments • Local tolerability was highly favorable as reported by patient and investigator assessments of irritation, burning, and stinging, consistent with safety profiles in prior trials Table 1. Baseline Demographics and Disease Characteristics Roflumilast Foam 0.3% (n=304) Vehicle (n=153) Age in years, mean (Std Dev) 43.2 (16.8) 41.8 (17.5) Sex Male, n (%) 153 (50.3) 75 (49.0) Female, n (%) 151 (49.7) 78 (51.0) Race, n (%) American Indian or Alaska Native 4 (1.3) 0 Asian 18 (5.9) 10 (6.5) Black or African American 36 (11.8) 15 (9.8) Native Hawaiian or Other Pacific Islander 0 1 (0.7) White 234 (77.0) 122 (79.7) More than 1 race 1 (0.3) 1 (0.7) Other 11 (3.6) 4 (2.6) Ethnicity, n (%) Hispanic or Latino 69 (22.7) 28 (18.3) Not Hispanic or Latino 235 (77.3) 125 (81.7) IGA score, n (%) 3 (moderate) 287 (94.4) 141 (92.2) 4 (severe) 17 (5.6) 12 (7.8) Erythema score, n (%) 2 (mild) 0 1 (0.7) 3 (moderate) 282 (92.8) 141 (92.2) 4 (severe) 22 (7.2) 11 (7.2) Scaling score, n (%) 2 (mild) 0 0 3 (moderate) 256 (84.2) 130 (85.0) 4 (severe) 48 (15.8) 23 (15.0) WI-NRS, mean score (Std Dev) 5.06 (2.34) 4.74 (2.29) WI-NRS score ≥4, n (%) 206 (67.8) 98 (64.1) BSA, mean % (Std Dev) 2.89 (2.03) 2.98 (2.57) Scalp, n (%) 291 (95.7) 136 (88.9) Face, n (%) 186 (61.2) 98 (64.1) Eyelids involved, n (%) 29 (9.5) 13 (8.5) Ears, n (%) 146 (48.0) 79 (51.6) Neck, n (%) 33 (10.9) 13 (8.5) Trunk, n (%) 28 (9.2) 18 (11.8) Other, n (%) 11 (3.6) 4 (2.6) BSA: body surface area; IGA: Investigator Global Assessment; Std Dev: standard deviation; WI-NRS: Worst Itch Numeric Rating Scale. Figure 2. IGA Success (0 or 1 With a 2-Grade Improvement) IGA Success = Clear or Almost Clear with at least a 2-grade improvement from baseline Intent-to-treat population; missing scores imputed using multiple imputations. Error bars represent 95% confidence interval. Statistical significance was concluded at the 1% significance level (2-sided). IGA: Investigator Global Assessment. REFERENCES 1. Dessinioti C, Katsambas A. Clin Dermatol. 2013;31:343–351. 2. Dong C, et al. J Pharmacol Exp Ther. 2016;358:413–422. 3. Zirwas M, et al. 30th Congress of the European Academy of Dermatology and Venereology (EADV) Virtual, September 29–October 2, 2021. INTRODUCTION • Seborrheic dermatitis (SD) is a common, chronic inflammatory skin disease that affects patients of all ages, with a global prevalence of approximately 5%1 • Treatment is via topical therapies, including antifungal agents and corticosteroids, which have limitations (side effects and/or inability to use on both hair-/non–hair- bearing areas) • Roflumilast is a selective phosphodiesterase 4 (PDE4) inhibitor with greater affinity for PDE4 than apremilast and crisaborole (25- to >300-fold more potent in in vitro assays)2 • Topical roflumilast is being investigated as a once-daily, nonsteroidal treatment for long-term management of psoriasis (FDA-approved July 29, 2022), atopic dermatitis, and SD • Efficacy, safety, and tolerability of roflumilast foam have been demonstrated in a phase 2a trial in SD3 and a subsequent open-label safety trial (NCT04091646/NCT04445987) • Here, we report the results of a phase 3 trial (NCT04973228) of roflumilast foam 0.3% in patients with SD METHODS • This phase 3 randomized, parallel-group, double-blind, vehicle-controlled trial was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or non-scalp areas (Figure 1) • The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8 RESULTS • Baseline patient demographics and disease characteristics were similar between the groups (Table 1) • Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved the primary efficacy endpoint of IGA Success (Figure 2) and IGA status of Clear (Figure 3) at Week 8 – Percentages of patients achieving IGA Success and IGA Clear at Weeks 2 and 4 were also greater with roflumilast • Significantly greater percentages of roflumilast- than vehicle-treated patients achieved secondary endpoints of: – WI-NRS Success at Weeks 2, 4, and 8 (Figure 4) – Overall Assessment of Erythema score of 0 (Figure 5) at Week 8 – Overall Assessment of Scaling score of 0 (Figure 5) at Week 8 • Local tolerability was favorable on investigator- and patient-rated assessments (Figure 6) • Overall incidence of treatment-emergent adverse events (TEAEs), serious adverse events, and TEAEs leading to discontinuation were low, with similar rates between roflumilast and vehicle (Table 2) Andrew Blauvelt,1 Javier Alonso-Llamazares,2 Neal Bhatia,3 Zoe D. Draelos,4 Janet DuBois,5 Seth B. Forman,6 Melinda Gooderham,7 Scott T. Guenthner,8 Adelaide A. Hebert,9 Edward Lain,10 Angela Y. Moore,11 Kim A. Papp,12 Linda Stein Gold,13 Matthew Zirwas,14 Saori Kato,15 Scott Snyder,15 David Krupa,15 Patrick Burnett,15 David R. Berk,15 David H. Chu15 1Oregon Medical Research Center, Portland, OR, USA; 2Driven Research LLC, Coral Gables, FL, USA; 3Therapeutics Clinical Research, San Diego, CA, USA; 4Dermatology Consulting Services, High Point, NC, USA; 5DermResearch, Inc., Austin, TX, USA; 6ForCare Medical Center, Tampa, FL, USA; 7SKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 8The Dermatology Center of Indiana, PC, and The Indiana Clinical Trials Center, PC, Plainfield, IN, USA; 9UT Health McGovern Medical School, Houston, TX, USA; 10Sanova Dermatology, Austin, TX, USA; 11Arlington Research Center, Arlington, TX, and Baylor University Medical Center, Dallas, TX, USA; 12Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 13Henry Ford Medical Center, Detroit, MI, USA; 14Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH, USA; 15Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA Efficacy and Safety of Roflumilast Foam 0.3% in Patients With Seborrheic Dermatitis in a Phase 3 Trial Figure 1. Study Design aAs this study is a single pivotal trial, the statistical significance of the primary endpoint was assessed at the 1% significance level (2-sided). To control for multiple testing, the 1% alpha was partitioned to 0.0033 for WI-NRS endpoints and 0.0067 for other secondary endpoints. BSA: body surface area; IGA: Investigator Global Assessment; QD: once daily; W: week; WI-NRS: Worst Itch Numeric Rating Scale. Endpointsa • Primary – IGA Success (0 or 1 with a 2-grade improvement) at W8 • Secondary: – IGA Success at W2 and W4 – IGA of Clear at W8 – WI-NRS at W2, W4, and W8 – Erythema Score of 0 at W8 – Scaling Score of 0 at W8 • Safety & tolerability Eligibility • Diagnosis of at least moderate seborrheic dermatitis (IGA >3) • Age ≥9 years • ≤20% BSA Roflumilast foam 0.3% QD (n=304) Vehicle QD (n=153) R a n d o m iz e 2:1 N=457 8 weeks dosing Figure 3. IGA Status of Clear (0) IGA Clear = IGA Score of 0. Intent-to-treat population; missing scores imputed using multiple imputations, P-values are not adjusted for multiple testing. Error bars represent 95% confidence interval. IGA: Investigator Global Assessment. Figure 4. WI-NRS Success Missing scores imputed using multiple imputations. Error bars represent 95% confidence interval. WI-NRS Success = ≥4-point improvement in patients with baseline WI-NRS score ≥4; evaluated at α=0.0033. Figure 5. Erythema and Scaling Scores of 0 Intent-to-treat population; missing scores imputed using multiple imputations. Error bars represent 95% confidence interval. Evaluated at α=0.0067. Table 2. Adverse Events n (%) Roflumilast Foam 0.3% (n=304) Vehicle (n=153) Patients with any TEAE 70 (23.0) 33 (21.6) Patients with any treatment-related TEAE 8 (2.6) 5 (3.3) Patients with any treatment-emergent SAEa 1 (0.3) 0 Patients who discontinued study due to AEb 2 (0.7) 3 (2.0) Most common TEAE (>1% in any group), preferred termc COVID-19 11 (3.6) 5 (3.3) Urinary tract infection 4 (1.3) 3 (2.0) Nausea 5 (1.6) 0 Nasopharyngitis 4 (1.3) 1 (0.7) Application-site pain 1 (0.3) 3 (2.0) Sinusitis 0 2 (1.3) aKeratoacanthoma, not in application site, deemed unrelated. bReasons for discontinuation in the roflumilast-treated group includes diarrhea/hematochezia/abdominal pain in one patient with a past history of Crohn’s and decreased potassium in the second patient. cPresented in descending order for overall rates. AE: adverse event; SAE: serious adverse event; TEAE: treatment-emergent adverse event. Figure 6. Local Tolerability Assessments (Safety Population) aScale for investigator-rated local tolerability: 0 = no evidence of irritation; 1 = minimal erythema, barely perceptible; 2 = definite erythema, readily visible; minimal edema or minimal papular response; 3 = erythema and papules; 4 = definite edema; 5 = erythema, edema and papules; 6 = vesicular eruption; 7 = strong reaction spreading beyond application site. bScale for patient-rated local tolerability: 0 = no sensation; 1 = slight warm, tingling sensation; not really bothersome; 2 = definite warm, tingling sensation that is somewhat bothersome; 3 = hot, tingling/stinging sensation that has caused definite discomfort. Week 2 Week 4 Week 8 P e rc e n ta g e o f P a ti e n ts Roflumilast Foam 0.3% Vehicle P<0.0001 P=0.0002 P<0.0001 Week 2 Week 4 Week 8 P e rc e n ta g e o f P a ti e n ts Roflumilast Foam 0.3% Vehicle P<0.0001 P=0.001 P<0.0001 Week 2 Week 4 Week 8 P e rc e n ta g e o f P a ti e n ts Roflumilast Foam 0.3% Vehicle P<0.0001 P=0.0053 P<0.0001 Week 2 Week 4 Week 8 P e rc e n ta g e o f P a ti e n ts Roflumilast Foam 0.3% Vehicle P<0.0001 P=0.0003 P<0.0001 ACKNOWLEDGEMENTS • This study was supported by Arcutis Biotherapeutics, Inc. • Thank you to the investigators and their staff for their participation in the trial. • We are grateful to the study participants and their families for their time and commitment. • Writing support was provided by Christina McManus, PhD, Alligent Biopharm Consulting LLC, and funded by Arcutis Biotherapeutics, Inc. 100% 98.9% 100%100% 100% 100% Baseline Week 4 Week 8 P a ti e n ts ( % ) 92.4% 96.1% 97.8%92.8% 92.7% 94.8% Baseline Week 4 Week 8 P a ti e n ts ( % ) Roflumilast Foam 0.3% (N=304) Vehicle Foam (N=153) n=296 n=151 n=277 n=140 n=264 n=136 ~80% of Patients Achieved IGA Success at Week 8 >50% of Patients Achieved IGA of Clear Week 2 Week 4 Week 8 P e rc e n ta g e o f P a ti e n ts Roflumilast Foam 0.3% (n=206) Vehicle (n=98) P=0.0001 P=0.0016 P=0.0007 100 80 60 40 20 0 100 80 60 40 20 0 >60% of Patients Achieved WI-NRS 4-pt Response 100 80 60 40 20 0 >50% of Patients Achieved Erythema=0 (None) 100 80 60 40 20 0 >50% of Patients Achieved Scaling=0 (None) 100 80 60 40 20 0 Patient-Rated Local Tolerability: % Patients With No or Mild Sensation Investigator-Rated Local Tolerability: % Patients With No Signs of Irritation 100 80 60 40 20 0 100 80 60 40 20 0 n=304 n=152 n=238 n=137 n=277 n=134 DISCLOSURES AB, JA-L, NB, AB, ZDD, JD, SBF, MG, STG, AAH, EL, AYM, KAP, LSG, and MZ are investigators and/or consultants for Arcutis Biotherapeutics, Inc. and received grants/research funding and/or honoraria; SK, DK, PB, DHC, and DRB are employees of Arcutis Biotherapeutics, Inc. Additional disclosures provided on request. Slide 1: Efficacy and Safety of Roflumilast Foam 0.3% in Patients With Seborrheic Dermatitis in a Phase 3 Trial