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The Topical Psoriasis Treatment Update FACULTY Linda F. Stein Gold, MD Director of Dermatology Research Division Head of Dermatology Henry Ford Health System Detroit, Michigan Medscape EDUCATION.

Medscape EDUCATION Misconception We Don't Need Anything Other Than Topical Corticosteroids.

How Well Do Potent Topical Corticosteroids Do As Monotherapy? Halobetasol and betamethasone dipropionate ointment • Adults with severe psoriasis up to 20% BSA • Before the start of treatment with topical corticosteroids, a 10% salicylic acid ointment was applied twice a day for 2 or 3 days to remove the scales • Treat BID for 28 days • Clear/almost clear in 40% of the patients treated with halobetasol and in 25% of those who received betamethasone dipropionate ointment These differences were not statistically significant BID, twice daily. Mensing H, et J Am Acad Dermatol. Pt These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Halobetasol Lotion 0.01% Approximately 40% Clear/AImost Clear Halobetasol lotion 0.01% (n-285) Vehicle 145) 70 60 20 10 Study Visit, wk Treatment success was defined as at least a 2-grade improvement in baseline IGA score and a score of O II. .003; tP< .001. IGA, Investigator Global Assessment Sugarman JL, et al. Cutis. 2019; 103: 111-116. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

100 75 8 50 25 Clobetasol Propionate spray 0.05% Clobetasol Spray Potent Efficacy But Tolerability Tradeoff 25 Cbbetasd propionate spray 0.0596 Vehicle O Almost clear Clear Vehicle spray 0.05% Week 4 20 15 10 Week I Week 2 Vehicle spray Week 4 Week 8 Week 2 The incidence of burning/stinging decreased throughout the study, from Subjects in the intent-to-treat population who were clear or weeks 1 to 4 and at week 8 (4 weeks after completion of treatment) based almost clear in overall disease severity at weeks 2 and 4. on the intent-to-treat population. Jarratt MT, et al. Cutis. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Medscape EDUCATION Misconception Fixed Combinations Add Nothing That I Can't Do by Combining Drugs Myself.

Combination Therapy Is Generally Better in Psoriasis Calcipotriene/Betamethasone[ll • Complimentary mechanism of action • Minimize side effects • Decrease irritation • Minimize atrophy Tazarotene/Halobetasol Lotiona • Complimentary mechanism of action Minimize side effects • Decrease irritation • Minimize atrophy 1. Patel NI.J, et al. Clin Cosmet Investig Dermatol. 2. Sugarman JL, et al. J Drugs Dermatol. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Why a Corticosteroid/Calcipotriene Combination in a Single Formulation Was a Challenge to Develop Corticosteroids and calcipotriene have optimal stability at different pH valuest1'21 Corticosteroids Stable under acidic conditions Affected by alkaline residues and oxidizing agents Calcipotriene • Affected by acidic residues and oxidizing agents Reacts with alcohol • and undergoes epimerization, thus degrading 14 7 pH • Differences in physiochemical properties and stabilities of corticosteroids and calcipotriene precluded their successful combination in a single formulation 1. Simonsen L, et al. Drug Dev Ind Pharm. 2004;30M095-1102; 2. Lind M, et al. Dermatol Ther (Heidelb). These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Combination Therapy Is Generally Better in Psoriasis Calcipotriene/Betamethasone Dipropionate • CAL/BDP cream with PADTM technology[l] Rapid onset Enhanced penetration Elegant vehicle • CAL/BDP foama Enhanced penetration Long term maintenance efficacy It is Medscape's policy to avoid the use of trade names in accredited activities. However, in an effort to be as clear as possible, a trade name is used in this activity to clarify and better describe the technology used by this It is not meant to promote any particular product. BDP, betamethasone dipropionate; CAL, calcipotriene 1. Selmer J, et al. SKIN: J Cutaneous 2. Lebwohl M, et al. Am Acad Dermatol- 2021 These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Cumulative Receptor Phase Levels of Tazarotene/ Tazarotenic Acid as a Percent of Applied Dose Halobetasol Cream With Tazarotene Cream in Upper Layer 0 o v 0.018 0.016 0.014 0.012 0.010 0.008 0006 0.004 0.002 0.000 Percent of Applied Dose, Mean + SD, N Halobetasol 0.05% Cream with Tazarotene 0.1% Cream in Upper Layer Tazarotene 0.1% Cream Time (Hours) 24 Tanghetti EA, et al. J Dermatolog Treat These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Combination Therapy Is Generally Better in Psoriasis Tazarotene/HaIobetasoI Lotion • Synergistic efficacy • Elegant formulation • Maintenance of effect off drug for at least 1 month Lebwohl MG, et al. J Am Acad Dermatol. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Medscape EDUCATION Misconception Nonsteroidal Options Cannot be Used as Monotherapy.

Non-Steroidal Efficacy Calcipotriene (8 weeks)t1'21 • Cream: 4% clear, 50% marked improvement[a] • Ointment: 11.3% clear, 70% marked improvement[b] Tazarotene (12 weeks)t31 • Gel 0.05%:2% clear, 28% marked improvement • Gel 0.1%:0% clear, 38% marked improvement • Cream did not isolate results for clear/almost clear 1. Calcipotriene cream, 0.005% [PII Revised March 2015; 2. Calcipotriene ointment, 0.005% [PII Revised May 2008; 3. Tazarotene gel 0.05%/0, 1% [PII Revised February 2011. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

The NEW ENGLAND JOURNAL of MEDICINE ESTABLISHED IN 1812 DECEMBER 9, 2021 VOL. 385 NO. 24 Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis Mark G. Lebwohl, M.D., Linda Stein Gold, M.D., Bruce Strober, M.D., Ph.D, Kim A. Papp, M.D., Ph.D., April W. Armstrong, M.D., Jerry Bagel, M.D., Leon Kircik, M.D., Benjamin Ehst, M.D., Ph.D., H. Chih-ho Hong, M.D., Jennifer Soung, M.D., Jeff Fromowitz, M.D., Scott Guenthner, M.D., Stephen C. Piscitelli, Pharm.D., David S. Rubenstein, M.D., Ph.D., Philip M. Brown, M.D.,J.D., Anna M. Tallman, Pharm.D., and Robert Bissonnette, M.D. Lebwohl MG, et al. N Engl J Med. 2021 ;3852219-2229. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Tapinarof 1% Once Daily Primary Endpoint of PGA Response at Week 12 0 60 50 35.4% 40 30 20 10 Tapinarof 1% QD (n-340) A 29.4% P<O.OOOI PSOARING 1 6.0% Vehicle QD (n-170) 40.2% Tapinarof 1% QD (n-343) A 33.9% P<O.OOOI PSOARING 2 6.3% Vehicle QD 172) PGA response ratea was highly statistically significant in the tapinarof cream 1% once daily group vs vehicle in both PSOARING 1 and 2: 35.4% vs 6.0% (P < .0001) and 40.2% vs 6.3% (P < .0001), respectively •PGA of O or 1 and 2 2-grade improvement at week 12. ITT P value based upon Ccxhran-Mantel-Haenszel analysis stratified by baseline PGA score. ITT, intent-to-treat; PGA, Physician Global Assessment; SEM, standard error of mean. Lebwohl M, et al. SKIN: J Cutaneous Med. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Phase 3 PSOARING Program Improvement in Peak Pruritus NRS of 4-Point Minimum 4-Point Improvement I Peak Pruritus NRS From Baseline to Week 12 (ITT, MI) 80 Tapinarof QD Vehicle Q D tp=o.0070 tp:o.0016 8 tp:o.0083 60.7 43.2 12 80 Tapinarof QD 40 20 tp=o.0707 2 60 40 20 tp:o.0204 2 tP<O.0001 4 tP<O.0001 8 WEEK PSOARING 2 tP<o.0001 56.9 29.7 12 WEEK PSOARING 1 NRS, numerical rating scale. Lebwohl M, et al. N Engl J Med. 2021;3852219-2229. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Tapinarof 1% Once Daily Adverse Event Profile Consistent With Previous Studies PSOARING 2 Tapinarof QD Vehicle QD • The most common (2 1% in any group) TEAEs: folliculitis, contact dermatitis, headache, pruritus, dermatitis • Folliculitis was mostly mild or moderate in severity in both studies and study discontinuation due to folliculitis was low: 1.8% (6/340) vs 0.0% (0/170) and 0.9% (3/343) vs 0.0% (0/172) in PSOARING 1 and 2, respectively Patients, n (%) PSOARING 1 Tapinarof QD Vehicle QD n = 340 n = 170 Most common treatment-related TEAEs (2 1 % in any group) Folliculitis Contact dermatitis Headache Pruritus Dermatitis 70 (20.6) 13 (3.8) 5 (1.5) 4 (1.2) 1 (0.3) Study discontinuation due to AESI Folliculitis Contact dermatitis Headache Mild Moderate Severe 6 (1.8) 5 (1.5) 1 (0.3) 2 (1.2) 1 (0.6) 1 (0.6) o (0.0) o (0.0) o (0.0) o (0.0) o (0.0) n = 343 54 (15.7) 16 (4.7) 1 (0.3) 2 (0.6) 4 (1.2) 3 (0.9) 7 (2.0) 2 (0.6) Severity of folliculitis, n (%) among subset of patients with AESI of folliculitis 51 (63.8) 28 (35.0) 1 (1.3) 1 (50.0) 1 (50.0) o (0.0) 44 (72.1) 17 (27.9) o (0.0) n = 172 1 (0.6) o (0.0) o (0.0) o (0.0) o (0.0) o (0.0) o (0.0) o (0.0) o (0.0) 1 (100.0) o (0.0) AE, adverse event; AESI, adverse event of interest; MedDRA, Medical Dictionary for Regulatory Activities; QD, once daily; TEAE, treatment-emergent adverse event Lebwohl M, et al. SKIN: J Cutaneous Med. 2020;4:s75. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Tapinarof PSOARING 3 Long-Term Open-Label Extension Trial Study Design PSOARING 1 PSOARING 2 PSOARING 3 Long-term open-label extension (40 weeks) Off-treatment Follow-up (4 weeks) Double-blind treatment (12 weeks) Tapinarof 1% QD n = 508 Vehicle QD (n = 255) PGA=O (n = 79) PGA 2 1 0=680) PGA = O stop treatment PGA 2 Off-treatment Re-start Tapinarof 1% QD Stop treatment entering PGA=O have treatrnent discontinued StarVCmtinue: entering with PGA21 are treated with tapinarof 1% OD until PGA=O Re-start: with worsening of psoriasis (PGA22) are retreated with tapinarof 1% QD until PGA=O (or unu 40) Patients with PGA of 2 (mild) and PGA of 4 (severe) limited to 10% each of the total randomized population; 80% of the total randomized population with PGA of 3 LTE, long-term extension. a. Lebwohl M, et al. SKIN. b. Strober B, et al. SKIN. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

PSOARING 3 Long-Term Extension Consistent Safety Profile With Short- or Long-Term Use Patients, n (%) TEAE TEAE with onset during PSOARING 3 TEAE ongoing at end of pivotals Treatment-related TEAE Study discontinuation due to TEAEs SAE Deaths Study discontinuation due to AESI Folliculitis Dermatitis contact Headache SAFI serious adverse event. StrotEr B, et al. J Am Acad Dermatol. Overall (N = 763) 474 (62.1 %) 431 (56.5%) 166 (21.80/0) 210 (27.5%) 41 (5.4%) 19 (2.5%) 1 (0.1%) 9 (1.2%) 11 (1.4%) PSOARING 3 Tapinarof Tapinarof 1% (N = 508) 321 (63.2%) 279 (54.9%) 138 (27.2%) 133 (26.2%) 26 (5.1%) 11 (2.2%) 1 (0.2%) 6 (1.20/0) 7 (1.40/0) Vehicle*Tapinarof 1% (N = 255) 153 (60.0%) 152 (59.6%) 28 (11.00/0) 77 (30.2%) 15 (5.9%) 8 (3.1%) 3 (1.20/0) 4 (1.60/0) These materjats are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

PSOARING 3 Long-Term Extension Disease Clearance and Control I Nearly 60% entering with PGA2 2 achieved PGA = 0 or 1 and 41% achieved PGA = 0 % Patients Achieving PGA of O or 1 (ITT, OC) 58.2% 10% Overall (n = 519) Key Points Tapinarof efficacy continues to improve beyond 12 weeks 58.2% patients who entered the LTE study with a PGA 2 2 achieved a PGA = 0 or 1 at least once during the study % Patients Achieving PGA of O (ITT, ocr 50% 20% 10% 40.9% Overall (n = 763) Key Points 41% of patients achieved total clearance of disease at least once in PSOARING 3 14.6% of subjects treated with tapinarof in the pivotal studies entered the LTE study with a PGA = O alncluding patients who entered with PGA = O (n = 79) and patients entering with PGA 2 1 who achieved PGA = O at least once during the study (n = 233). OC, observed cases. Strober B, et al. SKIN: J Cutaneous Med. 2021 These materials are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Medscape EDUCATION Misconception PDE4s Are Not Heavy Hitters.

Roflumilast Is a Highly Potent PDE4 Inhibitor Roflumilast has — 25- to > 300-fold higher potency in vitro than other approved PDE4 inhibitorstll IC50, nM Roflumilast Crisaborole Apremilast PDE4B2 cat 0.47 75 39 PDE4AIA 0.33 55 8.9 PDE4B1 0.28 61 16 PDE4C1 0.95 340 48 PDE4D7 0.53 170 12 Roflumilast is a well-established molecule and was the first FDA-approved PDE4 inhibitor as an oral formulation in 2011 to treat patients with severe COPDPI COPD, chronic obstructive pulmonary disease; IC50, half-maximal inhibitory concentration; PDE4, phosphodiesterase 4. 1. Dong C, et al. J Pharmacol Exp Ther. 2016;358413-422; 2. Li H, et al. Front Pharmacol. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Efficacy on IGA Success in Both Phase 3 Studies IGA Success DERMIS-I IGA Success DERMIS-2 100% 70% 20% 5.9% 2.1% Week 2 100% 70% .2 .2 20.6% 2.3% Week 4 33.3% 6.1% Week 6 42.4% 6.1% Week 8 3.3% 2.1% Week 2 19.1% 5.8% Week 4 25.6% 4.7% Week 6 37.5% 6.9% Week 8 00 Roflumilast 0.3% (n=286) Lebwohl M, et al. SKIN: J Cutaneous Med. 2021 Vehicle (n=153 • p<0.05; •• pcO.01; •t Roflumilast 0.3% (n=290) Vehicle n= These matenats are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Roflumilast Was Highly Effective for Intertriginous Plaques in DERMIS-I and DERMIS-2 I-IGA Success = clear or almost clear with at least a 2-grade improvement from baseline I-IGA Success and I-IGA Clear DERMIS-I I-IGA Success and I-IGA Clear DERMIS-2 100 90 80 70 50 30 20 10 34.5 20.7 3.3 Week 2 42.3 28.827.6 Week 4 56.6 49.1 2.2 4.8 Week 6 71.2 63.5 3.8 Week 8 100 90 80 70 60 50 30 20 10 34.7 30.6 6.5 3.2 Week 2 52.1 37.5 7.9 0.7 Week 4 57.8 42.2 3.8 0.3 Week 6 68.1 57.4 8.5 7.4 Week 8 Roflumilast 0.3% I-IGA Success Lebwohl M, et al. SKIN: J Cutaneous Med. 2021 Roflumilast 0.3% I-IGA Clear Vehicle I-IGA Clear Vehicle I-IGA Success • p<O.05; •• p<O.01; ••• p<O.001 These matenats are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Rapid Itch Response in Both DERMIS-I and DERMIS-2 Proportion of patients who achieved a 2 4-point improvement in WI-NRS from baseline score of 4 50 DERMIS-I DERMIS-2 100 90 80 70 50 34.9 22 20 10 Week 2 50.2 18 Week 4 57.8 22.2 Week 6 67.5 26.8 Week 8 100 90 80 70 40 30 20 10 41.9 21.1 Week 2 56.6 21.9 Week 4 62 30.6 Week 6 69.4 35.6 Week 8 z: Roflumilast 0.3% (n-218) Vehicle (n-115) Baseline mean (SD) WI-NRS: Roflumilast 0.3%5.7 (2.75) and Vehicle 5.7 (2.84) n Roflumilast 0.3% (n-229) Vehicle (n-116) Baseline mean (SD) WI-NRS: Roflumilast 0.3%5.8 (2.61) and Vehicle 6.1 (2.75) pco.01; ••• p«o.001 Robust reduction in itch occurs early and consistently improves throughout week 8 Lebwohl M, et al. SKIN: J Cutaneous Med. 2021 These matenats are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Yearlong Safety Study Summary of Adverse Events • 94% of AEs were rated mild or moderate • 97% of AEs were unrelated or unlikely to be related to treatment as determined by the investigator • Rates of Gl and psych AEs were low • 2 97% of patients had no evidence of irritation per physician assessment at each visit TEAE, n (0/0) Patients with any TEAE Patients with any treatment-related TEAE Patients with any SAE • Any treatment-related SAE Patients who discontinued study drug due to AE GI, gastrointestinal Stein Gold, L, et al. SKIN. 2021 Cohort 1 Total (N = 230) 104 (45.2) 7 (3.0) 10 (4.3) 11 (4.8) Cohort 2 Total (N = 102) 60 (58.8) 5 (4.9) 2 (2.0) 2 (2.0) Overall (N = 332) 164 (49.4) 12 (3.6) 12 (3.6) 13 (3.9) These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Medscape EDUCATION Misconception You Must Continue to Treat to See Efficacy: I Did Not Cure You!.

Tapinarof Phase 3 PSOARING LTE Interim Analysis Remittive effect for patients entering with PGA = O was 4 months • Remittive effect off-treatment was defined as maintenance of PGA 0 (clear) or 1 (almost clear) while off therapy after achieving complete disease clearance (PGA of 0) • The duration of remittive effect was likely an underestimate as the study end, not disease worsening, truncated the duration for some patients: Patients entering the study with PGA of O: 115 days (850; 162 op Patients entering the study with, or achieving, a PGA of O (n = 299): 119.3 days (81.8)b 0.8 0.3 0.1 Nurr&r at RSX Tapinud Piwtal) Vehide (P*otal) Remittive Effect: Maintenance of PGA of O or I While Off Therapy (ITT, OC) Median Duration of Remittive Effect: 115 days Crum (n•73) 325 44 40 s 4 125 29 32 TIME (DAYS) 73 25 3 28 19 22 13 16 12 3 10 3 6 3 9 3 •Kaplan-Meier estimated median, 95% confidence interval. bMean, standard deviation. B, et al. Presented at: Innovations in Dermatology 2021; Mar 16-20, 2021. Virtual Presentation. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

PSOARING 3 Long-Term Extension Long-Term Clinical Response and Remittive Effect of Tapinarof Cream 1% Overall, tapinarof is safe and well tolerated • Folliculitis occurred in approximately 15% in the pivotal studies and was mostly mild or moderate in severity; study discontinuation due to folliculitis was low in PSOARING 1 (1.8%) and 2 (0.9%) PSOARING 1 BASELINE PSOARlNG3 LTE PGA = 4 PASI = 19.8 PGA = 1 WEEK 12 PASI 3.8 WEEK 36 (LTE Week 24) Off Treatment for 12 weeksa PASI 1.2 PGA = I WEEK 48 (LTE Week 36) Off Treatment for 24 weeksa PASI 5.4 PGA = 2 PGA and PASI are global efficacy assessments. Example of I representative target lesion of a patient treated with tapinarof cream 1% QD in the PSOARING I and 3 trials. QTE week 24: Off treatment for 12 weeks; LTE week 36: Off treatment for 24 weeks; re-treatment at week 36 due to disease worsening. Strober B, et al. Poster presented at: Winter Clinical Dermatology Conference; January 14-19, 2022. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Tapinarof's Effect on Resident Memory T Cells EFFECT OF TAPINAROF ON RESIDENT MEMORY T CELLS (TRM) Tapinarof TAP ARNT TRM cell generation TRY cell survival Gene Expression TRM cell cytokine production (IL-17, IL-13, TNF-a) Resident Memory T Cells Significant reduction of TRN generation and survival TNF-a IL-17 IL-17 TNF-a Reduction of cytokine production by TRY Tapinarof's remittive effect may be attributed to its ability to reduce resident memory T-cell (TRM) generation, cytokine production (IL-17, IL-13, TNF-a), and survival as demonstrated by in vitro studies. AhR, aryl hydrccarmn receptor, ARNT, aryl hydræart:on receptor nuclear trans&ator, MW, molecular weight; Nrf2, nuclear factor erythroid 2-related factor 2; TAP, tapinarof, Th, T 1. Smith SH, et J Inv Dermatol. 2017;1372110-2119; 2. Furue M, et J Dermatological Sci. 3. B, et al. J Am Acad Dermatol. 2022;878W-O; 4. b.4mney N, et al. Presented at Society for Investigative Dermatology. tvlay 18-21 , 2022; 5. Negishi T, et al. J Immunol. 6. Tsui G, et al. J Invest Dermatol- 2012;132:59-68. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Long-Term Trial Design Roflumilast Cream Phase 2b (Trial #201; NCT03638258) Roflumilast Cream Phase 2 Long-term Safety (Trial #202; NCT03764475) Eligibility • Diagnosis of at least mild plaque psoriasis • Age 218 years • 2-20% BSAå N-331 Roflumilast cream 0.3% QD Roflumilast cream 0.15% QD Vehicle 12 weeks Completed Trial #201 through 12 weeks Eligibility • Diagnosis of at least mild plaque psoriasis for at least 6 months • Age 218 years • 2-25% BSAa Cohort I (Rollovers) Roflumilast cream 0.3% QD (n-230) 52 weeks Patients could stop applying treatment to lesions that cleared Patients could completely stop treatment when PASI and IGA = O following an office visit Treatment could be resumed when patient-observed psoriasis recurred Cohort 2 (Naive) Roflumilast cream 0.3% QD (n=102) Endpoints Primary: Safety • Occurrence of TEAEs • Occurrence of SAES Secondary: Efficacy • IGA clear or almost clear • Intertriginous-IGA clear or almost clear • PASI • BSA aExcIudes scalp, palms, soles. BSA, body surface area; IGA, Investigator Global Assessment; PASI, Psoriasis Area Severity Index; SAE, serious adverse event; TEAE, treatment-emergent adverse event Lebwohl M, et al. SKIN: J Cutaneous Med. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Median Duration of IGA of Clear or Almost Clear 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.0 At risk *"57.1% (n=185) of patients achieved IGA 0/1 during the trial; patients have a 500/0 probability of a duration of IGA of Clear or Almost Clear of more than 10 months (40.1 weeks) + Censored o 185 4 170 8 166 12 139 16 20 24 28 32 36 40 44 48 Duration of IGA Clear or Almost Clear (Weeks) 123 114 101 93 82 69 63 41 37 52 8 56 5 60 2 64 Duration of IGA 0/1: the time from the first observation of IGA 0/1 to the first subsequent time a patient's IGA is not IGA 0/1 _ Patients who received vehicle in parent study and rolled over into Study 202 with a 0/1 assessment are excluded from this analysis (N = 324). Lebwohl M, et al. SKIN: J Cutaneous Med. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Medscape EDUCATION Misconception Scalp Psoriasis Is Impossible to Treat.

Complex Treatment of Scalp Psoriasis • Scalp psoriasis presents as a significant burden to patients due to the difficult-to-treat nature of the site • Data suggest discussions about patient-preferred topical formulation may be a way to improve patient quality of life and increase treatment adherence • Additionally, UVB and excimer phototherapy via handheld device or with the addition of a blow dryer to separate the hair has been efficacious in clearing of scalp plaques • Etanercept, adalimumab, infliximab, brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, risankizumab, mirikizumab, ustekinumab, and apremilast all have demonstrated varying levels of efficacy in the scalp and are suitable first-line options for patients with scalp plaques plus whole-body psoriasis • A practical treatment algorithm, derived from the most up-to-date empirical evidence, is also presented for mild-to-moderate scalp psoriasis, severe scalp psoriasis, and scalp psoriasis with moderate-to-severe whole-body involvement Mosca M, et al. Dermatol Ther (Heidelb). 2021; 11769-797. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Roflumilast Foam for Scalp Psoriasis 60% of Patients Achieved S-IGA Success at Week 8 Significant Efficacy was Demonstrated as Early as Week 2 100% p = omo 17.4% 3.1% Week 2 p < omm 41.3% 5.6% Week 4 O Roflumilast foam 0.3% D Vehicle foam p < 0.0001 59.1% 11.4% Week 8 34.3% of patients on roflumilast achieved S-IGA = 0 (clear) vs 3.4% on vehicle S-IGA Success = clear or almost clear plus 2 2-grade improvement from baseline. Moore AY, et al. SKIN: J Cutaneous Med. 2021 ;5:s43. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Significantly More Roflumilast-Treated Patients had SI-NRS 4-Point Response as Early as Week 2 > 70% of Patients Achieved a SI-NRS 4-point Response at Week 8 100% 40% 20% 10% p < 0.0001 44.6% 15.6% Week 2 p<O.Ø01 62.0% 22.1% Week 4 o Roflumilast foam 0.3% a Vehicle foam p<O.OØJ 71.0% 18.5% Week 8 Evaluated in patients with SI-NRS Score 2 4 at baseline. Intent-to-treat population. SI-NRS: Scalp Itch-Numeric Rating Scale. Moore AY, et al. SKIN: J Cutaneous Med. 2021 These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Medscape EDUCATION Topical Therapy Remains the Cornerstone of Treatment and Our Treatment Paradigm.

A MeclSCape CONFERENCE uuauu •uuuuuuuuuuuuuuuu••••• THANK YOU 7/11///////[// l}// 1/1/1/1]// S.

New Data in Biologics FACULTY Bruce E. Strober, MD, PhD Clinical Professor Yale University Central Connecticut Dermatology Co-Scientific Director of the Corrona Psoriasis Registry Secretary-Treasurer of the International Psoriasis Council Editor-in-Chief, Joumal of Psoriasis and Psoriatic Atthritis Cromwell, Connecticut EDUCATION.

Medscape EDUCATION Generalized Pustular Psoriasis.

Effisayil 2: Phase 2, Randomized, Dose-Ranging Trial of the IL-36 Receptor Antagonist Spesolimab for Preventing Flares in Patients With a History of GPP N = 123 Screened N = 157 Day —84 to —1 High-dose spesolimab mg SC loading dose, 300 mg SC q4w Medium-dose spesolimab 600 mg SC loading dose, 300 mg SC q12w Low-dose spesolimab 300 mg SC loading dose, 150 mg SC q12w Placebo SC loading dose, SC q4w Response aner c, o LU o In event Of nares OL spesolimab 12 weeks during RCT peri0d 900 mg IV single dose OL spesolimab SC 300 mg SC q12wa Primary endpoint: Time to GPP flare by week 48 Key secondary endpoint: Occurrence of 2 1 GPP flare by GPP flare was defined as an increase in the GPPGA total by 2 2 from baseline and GPPGA pustulation by 2 2. The use of medication with IV OL spesolimab or other investigator-prescribed medication was considered to be a GPP flare Persistent flare after I week Day 1 Optional: OL spesolimati 900 mg IV single dose Week 44 Week 48 *Patients receiving OL spesolimab 300 mg SC q12w had the option to escalate to 300 mg SC q4w if there was an increase in the pustular component of GPPGA 1 from any of the previous OL visit(s). blncrease in GPPGA total score by 2 from baseline and GPPGA pustulation subscore by 2. GPP, generalized pustular psoriasis; GPPGA, Generalized Pustular Psoriasis Physician Global Assessment; IL, interleukin; IV, intravenous; OL, open-label; OLE, open-label extension; RCT, randomized controlled trial; SC, subcutaneous. Morita A, et al. Dermatol Ther (Heidelb). Strober B, et al. Presented at: WCD 2023. Late-breaking oral presentation. These materials are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Effisayil 2: Key Baseline Characteristics and Time to GPP Flare During 48 Weeks of Spesolimab Treatment Time to GPP flare up to week 48 GPP flares/year, n Weight, kg IL36RN mutation Yes No Unknowna Low (n = 31) 2.7±2.3 71.1 ±23.6 7 (23) 17 (55) 7 (23) Spesolimab SC Medium (n = 31) 1.9±0.9 71.5±23.0 10 (32) 15 (48) 6 (19) High (n = 30) 2.4 ±1.9 68.7 ±22.9 7 (23) 19 (63) 4 (13) Placebo (n = 31) 2.4±1.2 75.7±23.9 4 (13) 22 (71) 5 (16) 10 08 06 0.4 02 00 Patients at risk (n) Placebo Spesolimab low Spesolimab medium Spesolimab high PIO P25 (weeks) (weeks) Median (weeks) 373 Placebo Spesolimab low Spesolimab medium Spesolimab high 1.9 4.1 4.1 3.3 17.0 nc Data are n (%) or mean ±SD. aNo sample obtained 84% reduction in risk for flare development with high-dose spesolimab (HR 0.16; 95%0.05, 0.54; P = .0005) No flares after week 4 31 31 31 30 4 23 29 29 26 8 20 25 25 26 12 16 20 24 28 32 36 Tme (weeks) from first dose 20 24 24 26 19 24 24 26 17 24 21 26 17 24 21 25 17 24 21 24 17 24 21 23 16 24 21 22 40 15 24 21 22 44 15 24 21 22 48 11 21 14 18 Hazard ratios (95% Cl) for the medium- and low-dose spesolimab arms were 0.47 (0.21, I and 0.35 (O. 14, 0.86), respectively; statistical significance was not reached for medium-dose spesolimab, and was not tested for low-dose spesolimab. PIO, estimated probability of GPP flare = O. I; P25, estimated probability of GPP flare = 0.25; nc, not calculated. Strober B, et al. Presented at WCD 2023. Late-breaking oral presentation. These materials are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Effisayil 2: Occurrence of at Least 1 GPP Flare by Week 48 With Spesolimab Occurrence of 21 GPP flare by Week 48 (MP) 100 80 60 40 29.7 20 22.6 12.7 Spesolimab Spesolimab Spesolimab Nb/N low 7/31 medium 9/31 high 3/30 51.6 Placebo 16/31 High-dose spesolimab was superior to placebo with a 39% delta in flare occurrence (95% Cl -0.62, -0.16; P = .0013)c •A multiple imputation method for binary endpoints with monotone missing assessments using sequential logistic regression method was utilized. bBefore imputation. 'Risk differences (95% CI) for medium- and low-dose spesolimab were —0.23 (—0.46, 0.01) and —0.31 (—0.54, —0.08), respectively; statistical significance was not tested for. Strober B, et al. Presented at WCD 2023. Late-breaking oral presentation. These materials are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

BE READY: PASI 90 Responses at Week 16 and Following Bimekizumab Withdrawal, Treatment History, and Safety PASI 90 at Week 16 and Week 52 (ITT NRI) • Patient groups were balanced for all baseline characteristics Placebo (n = 86) BKZ (n = 349) Prima end oint 908 BKZ q4w—.placebo (n = 105) BKZq4w (n = 106) . BKZ q4w—q8w (n = 100) 100 80 60 40 20 91 .o 868 cebo- relapse weeks 162 Week 52 Prior medication use Any systemic Any biologic IL-17 inhibitor TNF inhibitor IL-12/23 inhibitor IL-23p19 inhibitor Data are n (%) Safety Oral candidiasis BKZ q4w edian time t < PASI 75) — 12 Week 16 Weeks O -16 Placebo BKZ q4w Placebo (n = 86) 71 (83) 37 (43) 18 (21) 12 (14) 11 (13) Weeks 16 — 56 BKZ q4w BKZ q4w—q8w BKZ BKZ q4w (n = 349) 276 (79) 154 (44) 85 (24) 62 (18) 40 (12) 28 (8) 12 (11%) o 21 (6%) • IBD: No patients up to week 56 *P < ml , calculated using Cochran-Mantel-Haenszel test from the general association. tNominal P < .001 vs placebo. PASI, Psoriasis Area and Severity Index. Gordon K, et al_ Presented at: AAD 2020. Late-breaking presentation: Clinical trials. These materials are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

BE RADIANT OLE: Maintenance of Response and Safety Through Weeks 48 to 144 With Bimekizumab in Patients With Psoriasis Patients included in analysis PASI responses through week 144 in patients who entered OLEb (mNRlC) Initial treatment period randomized to BKZ q4w or SKB q4w Maintenance treatment period BKZ q4w, BKZ q8w, or SKB 4w 100 75 50 25 PASI 2 Start of OLE 194 84 Switch toBKZ : PASI 100 Start of OLE 93 93 90 87 100 75 50 25 o 77 71 69 69 Open-label extension perioda Continuous BKZ (n = 336) SKB/BKZ (n = 318) Low incidence of SAEs and discontinuations Observed mNRF, % NRI, % 0 8 16 Week cont. BKZ SKB/BKZ Cont. BKZ SKB/BKZ Cont. BKZ SKB/BKZ 24 : — Continuous BKZ (n = 336) SKB/BKZ (n = 318) 32 40 48 56 64 72 80 88 96 104112120128136144 8 16 Switch : to BKZ 24 32 40 48 56 64 72 80 88 96 104112120128136144 Weeks 94 (310/329) 84 94 84 92 83 95 (294/308) 96 (275/286) 93 93 88 87 144 93 (264/283) 91 (245/268) 90 79 77 75 (248/329) 53 (167/314) 75 53 74 53 74 (229/308) 82 (234/286) 71 77 68 74 144 76 (215/283) 76 (204/268) 69 69 64 64 aEfficacy analyses include continuous BKZ and SKB/BKZ groups, safety analyses include both groups pooled (BKZ total); bData for patients who entered OLE only (all patients received BKZ); cMissing data imputed using modified NRI = patients who discontinued due to lack of efficacy or treatment-related AEs were considered nonresponders at subsequent timepoints; multiple imputation was used for all other missing data BKZ, bimekizumab; mNRl, modified nonresponder imputation; NRI, nonresponder imputation; OLE, open-label extension; SAE, serious adverse event; SKB, secukinumab. Strober B, et al. Presented at: AAD 2023. Presentation P43778. These materials are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

Post-Hoc Analysis of 5 Phase 3/3b Trials Maintenance of PASI 90 Response With Bimekizumab Through 2 Years Among Week-16 PASI 90 Responders • Pooled analysis of 2-year data from BE VIVID, BE READY and BE SURE (and their OLE), BE BRIGHT, and BE RADIANT • Included patients randomized to BKZ 320 mg q4w to week 16, then either BKZ q4w or q8w until OLE entry (week 48/52/56; year 1), then patients received BKZ q4w or q8w based on PASI response and prior maintenance dose • 86.9% (1184/1362) of BKZ-randomized patients achieved PASI 90 at week 16 (NRI) Loss of response among Week 16 PASI 90 responders over 2 years (mNRP) Week 16 PASI 90 responders (N = 995) 0% 82 Never lost a respnse Lost response at 1 visit 8 Lost response at 2 visits Lost response at > 2 visits 100% Patients (%) amNRI: Patients who discontinued treatment due to lack of efficacy or TEAEs were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data Blauvelt A, et al. Presented at: WCD 2023. Poster. These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..

BE RADIANT: mNAPSl Response Rates Through Week 48 in Patients Treated With Bimekizumab or Secukinumab Patients achieving mNAPSl O SKB (n = 99) • BKZ total (n = 116) oc. 64 NRI: 62 c 53 —•—SKB OC -•-.SKB mNRla 100 ...a••• SKB NRI mNRla ...a•.• BZ NRI 80 60 40 20 o OC/mNRl/NRl: 33 C/mNRl/NR197 SKB BKZ 8 33/99 31/114 16 24 Week mNRl: 64 50 49/92 72/112 32 40 oc:77 mNRl: 74 NRI: 71 öC61 mNRl: 58 NRI:54 53/87 82/107 48 •For mNRl, patients who discontinued study treatment due to lack of efficacy or adverse events deemed treatment-related by investigators were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data mNAPSI, modified Nail Psoriasis Severity Index. Eyerich K, et al. Presented at: AAD 2023. Presentation P43878. These materials are provided to you solety as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited..