An Update on Drugs in Dermatology 2020 – 2021 Charles W. Lynde, MD, FRCPC, DABD Medical Director, The Lynde Institute for Dermatology & Lynderm Research Inc. Associate Professor, University of Toronto, Department of Medicine Dr. Charles W. Lynde has been a speaker, consultant and/or private investigator for:

AbbVie, Allergan, Amgen, Aralez, Arcutis, Bausch Health, Bayer, Boehringer Ingelheim, Celgene, Cipher, Dermavant, Eli Lilly, Galderma, Genentech, Glenmark, GSK, Innovaderm, Janssen, Kyowa, L’Oreal, LeoPharma, Merck, Medexus, Mylan, , Pediapharm, Pfizer, Procter and Gamble, Roche, Sandoz, Sanofi Adventis, Sanofi Genzyme, Stiefel, TEVA, Valeant. Objectives

1.To be familiar with the key dermatological therapeutics of 2020 and what’s in the pipeline 2.To translate this information into changing dermatologic clinical practice Disrupter of 2020: COVID-19 COVID-19 has changed the way we practice medicine, how clinical trials operate and our personal lives

Overview

1.Vaccines 8. Skin Cancer 2. 9. Vitiligo 3. 10. Alopecia 4.Palmoplantar Pustulosis 11. Anesthetic 5.Hidradenitis Suppurativa 12. Urticaria 6.Hand Dermatitis 7.Acne Vaccines Vaccines for COVID-19 As of November 2nd 2020 As of November 2nd 2020 there were there are 254 Active, Upcoming or 1,989 Active, Upcoming or Recruiting Trials Recruiting Trials and 273 Total Trials listed under listed under Vaccines COVID-19 on clinicaltrials.gov on clinicaltrials.gov 12.8% of all active, upcoming or recruiting vaccine trials are for COVID-19 Atopic Dermatitis Atopic Dermatitis

As of November 2019 there As of October 30, 2020 there were are 855 trials 961 trials listed under listed under Atopic Dermatitis Atopic Dermatitis on clinicaltrials.gov on clinicaltrials.gov Atopic Dermatitis

•New biologics •New small molecules •New topicals Pathogenesis

Guttman-Yassky, Emma, et al. “New Era of Biologic Therapeutics in Atopic Dermatitis.” Expert Opinion on Biological Therapy, vol. 13, no. 4, 2013, pp. 549–561., doi:10.1517/14712598.2013.758708. Atopic Dermatitis

Marked ….. ? the Barrier most Interpla Defect y important

Microbio Immune me Defects Moisturizers

• May be sufficient for mild disease • Should be applied liberally and often • Choice depends on individual preference • Should be effective, free of potential sensitizers, inexpensive TikTok Famous Biologics for Atopic Dermatitis

• • September 2019: NOC Health Canada for > 12 years • May 2020: FDA Approval for 6-11 years • ANB020 • GBR 830-204 • KHK4083 • • • Nemolizumab • Dupilumab Phase 3 Trial: (LIBERTY AD PEDS) ≥ 6 to < 12 y/o

IGA (0,1) at Week 161 EASI-75 at Week 161

100% †P=0.0004 100% ‡P<0.0001 ‡P<0.0001

80% 80% 67% 70%

60% 60%

40% 40% 33% 30% 27% Percentage of Patients Percentage of Patients 20% 20% 11%

0% 0% Placebo Dupilumab Dupilumab Placebo Dupilumab Dupilumab 100/200 mg 300 mg 100/200 mg 300 mg q2w q4w q2w q4w

These data represent interim results from the trial. The efficacy and safety of dupilumab in children below the age of 12 have not currently been reviewed by a regulatory authority. EASI-75, improvement of ≥75% on Eczema Area and Severity Index score; IGA, Investigator’s Global Assessment; q2w, every 2 weeks; q4w, every 4 weeks. 1. Sanofi. https://www.sanofi.com/en/media-room/press-releases/2019/2019-08-06-07-05-00. Accessed August 6, 2019.

GZCA.DUP.20.05.0158 Dupilumab Other Investigations

• Severe Chronic Hepatic • Safety in Pregnancy Pruritus • Eosinophilic Esophagitis • Rhinosinunitis in Sleep Apnea • Localized Scleroderma Patients • Asthma • Severe Chronic Hand Eczema • Bullous Pemphigoid • Aspirin Excerbated Respiratory Disease • Prurigo Nodularis • Peanut Allergy • Atopic keratoconjunctivits ANB020 / Etokimab (Anaptysbio)

• Indication: Moderate-to-Severe AD • MoA: IL-33 Inhibitor • Active: • Phase 2: A Study Investigating the Efficacy, Safety, and PK Profile of ANB020 Administered to Adult Subjects With Moderate-to-Severe AD (ATLAS) • Other indications being investigated: Eosinophilic Asthma, Peanut Allergy, Chronic Rhinosinusitis

ClinicalTrials.gov GBR 830 / GBR 830-204 (Glenmark)

• Indication: Atopic Dermatitis • MoA: IgG1 antibody specific for OX40 (CD134) • Active: • Phase 2b: Treatment of Adult Subjects • Administration: Subcutaneous injection • Other indications being investigated: None

ClinicalTrials.gov KHK4083 (Kyowa)

• Indication: Atopic Dermatitis • MoA: Anti OX40 • Active: • Phase 2: Treatment of Adult Subjects • Administration: Subcutaneous injection • Other indications being investigated: Ulcerative Colitis

ClinicalTrials.gov Tralokinumab (LEOPharma)

• Indication: Atopic Dermatitis • Expected Launch: US (FDA) ? Q2 2021 • MoA: IL-13 Inhibitor • Currently Recruiting / Upcoming: • Phase 2: Skin Barrier Function • Phase 3: In Combination with Topical Corticosetoids • Phase 3: Long Term Extension • Administration: subcutaneous injection • Other indications being investigated: alopecia areata, ulcerative colitis, asthma, pulmonary fibrosis COMING SOON

ClinicalTrials.gov Lebrikizumab / DRM 06 (Dermira)

• Indication: Atopic Dermatitis • MoA: IL-13 Inhibitor • Currently Recruiting: • Phase 3: Long-term Safety and Efficacy • Phase 3: Efficacy and Safety in Adults • Phase 3: Safety and Efficacy of in Adolescents • Phase 3: In Combination with Topical Corticosteroid • Administration: subcutaneous injection loading dose, followed by Q2W or Q4W • Other indications being investigated: Asthma, COPD, Idiopathic Pulmonary Fibrosis

ClinicalTrials.gov Nemolizumab / CD14152

• Indication: Atopic Dermatitis • MoA: IL-31 Inhibitor • Currently Recruiting: • Phase 3: Long-term Safety and Efficacy • Phase 3: Efficacy and Safety in Adults • Phase 3: Safety and Efficacy of in Adolescents and Adults • Administration: subcutaneous injection • Other indications being investigated: prurigo nodularis

ClinicalTrials.gov Tezepelumab / Amgen 20170755 (AMGEN)

• Indication: Atopic Dermatitis • MoA: TSLP (Thymic Stromal Lymphopoietin) Inhibitor • STOPPED JULY 2020 – DID NOT MEET PRIMARY ENDPOINTS • Phase 2b: A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy • Administration: Subcutaneous injection with a treatment period of 52 weeks • Other indications being investigated: Severe Asthma, Asthma, COPD, Bronchial Disease, Respiratory Tract Diseases, and Respiratory Hypersensitivity, Chronic Spontaneous Urticaria

ClinicalTrials.gov In 2018 we met JA(C)K (Lynde) Last year JAK was older and wiser This year JAK is in JK… he has matured Small Molecules

• Abrocitinib – JAK-1 Inhibitor • Baricitinib – Selective JAK-1 Inhibitor • Brepocitinib – TYK2/JAK1 • LEO LP0190 – H4 Inhibitor • Upadacitinib – Selective JAK-1 Inhibitor • ZPL389 – H4 Inhibitor PF-04965842 / Abrocitinib (Pfizer)

• Indication: Moderate-to-Severe AD • MoA: JAK-1 Inhibitor • Recruiting / Active: • Phase 3: Compared With Dupilumab in Adults With Moderate to Severe Atopic Dermatitis on Background Topical Therapy • Phase 3: Without Topical Medications in Subjects Aged 12 Years and Older • Other indications being investigated: Hepatic Impairment, Psoriasis • Launch: ? Q2 2021

“Search of: PF-04965842 - List Results.” Search of: PF-04965842 - List Results - ClinicalTrials.gov, clinicaltrials.gov/ct2/results?cond=&term=PF-04965842&cntry=&state=&city=&dist=. Non-head-to-head comparison of various novel treatment efficacy for moderate to severe AD EASI 75 (Week 12*/16)

PBO UPA 7.5mg UPA 15mg UPA 30mg Column3 UPA 7.5mg2 UPA 15mg3 UPA 30mg4 Column1 PBO4 Abro 100mg Abro 200mg Column15 PF5842 100mg2 PF5842 200mg23 Column12 PBO2 SOLO 1 Dupi Q2W PBO3 SOLO 2 Dupi Q2W Column4 SOLO 1 Dupi Q2W2 SOLO 2 Dupi Q2W2 Column2 PBO42 Bari 2mg Bari 4mg Column5 Bari 2mg6 Bari 4mg7

100% MONOTHERAPY STUDY MONOTHERAPY STUDY MONOTHERAPY STUDIES COMBO STUDY WITH Phase 2 Phase 3 Phase 2 VARIABLE TCS USE IN PBO & BARI GROUPS Phase 2 75%

50%

25%

0% RAW DATA PLACEBO ADJ RAW DATA PLACEBO ADJ RAW DATA PLACEBO ADJ RAW DATA PLACEBO ADJ RINVOQ ABROCITINIB* DUPILUMAB BARICITINIB

For Reference Only: Not From Head to Head Trials. Dupilumab Phase 3 vs Upadacitinib Phase 2 vs Baricitinib Phase 2 vs Abrocitinib Phase 2 Baricitinib / LY3009104 (Eli Lilly)

• Indication: Moderate-to-Severe AD • Administration: Oral • MoA: JAK1/2 Inhibitor • Recruiting / Active: • Phase 3: Children and Adolescents With Atopic Dermatitis • Phase 3: With Topical Corticosteroids in Adults That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine • Phase 3: A Study of Long-term Baricitinib (LY3009104) Therapy in Atopic Dermatitis (BREEZE-AD3) • Other indications being investigated: RA, Giant Cell Areritis, Liver Disease, AA • Launch: ? Q4 2020 / 2021

ClinicalTrials.gov Brepocitinib / PF-06700841 (Pfizer)

• Indication: Moderate-to-Severe AD • Administration: Oral • MoA: TKY2/JAK1 • Completed: • Phase 2: Dose Ranging Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of PF-06700841 Topical Cream in Participants With Mild or Moderate Atopic Dermatitis • Other indications being investigated: SLE, Crohn’s, PsO, PsA, UC, AA

ClinicalTrials.gov Upadacitinib / M16-045 (Abbvie)

• Indication: Moderate-to-Severe AD • Administration: Oral dose with a treatment period of 16 weeks and a blinded extension period up to 3 years • MoA: JAK-1 Selective Inhibitor • Recruiting / Active: • Phase 3: Open-Label Extension Study • Phase 3: Evaluation of Upadacitinib in Adolescent and Adult Patients • Phase 3: In Combination With Topical Corticosteroids in Adolescent and Adult Participants • Phase 1: Safety and Tolerability of Upadacitinib in Pediatric Participants • Other indications being investigated: Ulcerative Colitis, Juvenile Idiopathic Arthritis, , Crohn’s Disease, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Giant Cell Arteritis, and • Launch: ? 2021

ClinicalTrials.gov Co-Primary Endpoint: vIGA-AD 0/1a at Week 16

Placebo UPA 15 mg UPA 30 mg

100%

* 75% * * * 62% 59% 52% * 50% 48% * 39% 40%

25% Percent of patients Percent 11% 8% 5% 0% N=281 N=281 N=285 N=278 N=276 N=282 N=304 N=300 N=297 Measure Up 1 Measure Up 2 AD Up Monotherapy Monotherapy Combination Therapy - Plus TCS *p≤0.001 vs placebo; ITT (NRI-C) a) vIGA-AD 0/1 is defined as a validated Investigator Global Assessment for Atopic Dermatitis of clear or almost clear (0/1) with at least two grades of reduction from baseline. Upadacitinib is an investigational drug for atopic dermatitis. Efficacy and safety have not been established. Press release, https://news.abbvie.com/article_display.cfm?article_id=12153, ABVRRTI70713, accessed July 28, 2020 Press release, https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-monotherapy-meets-all-primary-and-secondary-endpoints-in-second-phase-3-study-for-atopic-dermatitis.htm, ABVRRTI70838, accessed July 28, 2020 Press release, https://news.abbvie.com/news/press-releases/third-pivotal-phase-3-study-shows-rinvoq-upadacitinib-plus-topical-corticosteroids-improves-skin-and-itch-symptoms-in-atopic-dermatitis-patients.htm?view_id=4741, ABVRRTI70869, accessed July 28, 2020

36

Secondary Endpoint: Improvement in Worst Pruritus NRS ≥4a at Week 16

Placebo UPA 15 mg UPA 30 mg

100%

* 75% * * 64% * 60% 60% * 52% * 52% 50% 42%

25% 15% Percent of patients Percent 12% 9%

0% N=281 N=281 N=285 N=278 N=276 N=282 N=304 N=300 N=297 Measure Up 1 Measure Up 2 AD Up Monotherapy Monotherapy Combination Therapy - Plus TCS *p<0.001 vs placebo; ITT (NRI-C) a) Improvement in Worst Pruritus NRS≥4 is defined as a reduction in Worst Pruritus Numerical Rating Scale (NRS) ≥4 compared with baseline (for participants with NRS ≥4 at baseline).

Upadacitinib is an investigational drug for atopic dermatitis. Efficacy and safety have not been established. Press release, https://news.abbvie.com/article_display.cfm?article_id=12153, ABVRRTI70713, accessed July 28, 2020 Press release, https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-monotherapy-meets-all-primary-and-secondary-endpoints-in-second-phase-3-study-for-atopic-dermatitis.htm, ABVRRTI70838, accessed July 28, 2020 Press release, https://news.abbvie.com/news/press-releases/third-pivotal-phase-3-study-shows-rinvoq-upadacitinib-plus-topical-corticosteroids-improves-skin-and-itch-symptoms-in-atopic-dermatitis-patients.htm?view_id=4741, ABVRRTI70869, accessed July 28, 2020

37 Measure Up 1, Measure Up 2, and AD Up Study Results Summary

• The co-primary and all key • No new UPA safety risks • Full results from these studies secondary endpoints were observed compared to the will be presented at a future met (all achieved p<0.001) safety profile observed in medical meeting and/or for UPA 15mg and 30mg patients with RA and PsA published in a peer reviewed doses receiving UPA publication • UPA 30mg showed • No deaths, VTE or MACE numerically higher results were reported in the UPA than UPA 15mg for co- treatment arms primary and all key secondary endpoints

Upadacitinib is an investigational drug for atopic dermatitis and psoriatic arthritis. Efficacy and safety have not been established.

Press release, https://news.abbvie.com/article_display.cfm?article_id=12153, ABVRRTI70713, accessed July 28, 2020 Press release, https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-monotherapy-meets-all-primary-and-secondary-endpoints-in-second-phase-3-study-for-atopic-dermatitis.htm, ABVRRTI70838, accessed July 28, 2020 Press release, https://news.abbvie.com/news/press-releases/third-pivotal-phase-3-study-shows-rinvoq-upadacitinib-plus-topical-corticosteroids-improves-skin-and-itch-symptoms-in-atopic-dermatitis-patients.htm?view_id=4741, ABVRRTI70869, accessed July 28, 2020 LP0190 / JW1601 (LEOPharma)

• Indication: Moderate-to-Severe AD • Administration: Oral dose with a treatment period of 16 weeks and a blinded extension period up to 3 years • MoA: H4 Inhibitor • Completed: • Phase 1: Single and Multiple Ascending Dose Study of JW1601 for Healthy Volunteers

ClinicalTrials.gov Topicals

•Crisaborole – PDE-4 Inhibitor •Delgocitinib – JAK Inhibitor •INCB018424 – JAK Inhibitor •PF-07038124 – PDE-4 Inhibitor

ClinicalTrials.gov Crisaborole (Pfizer)

• Indications: mild-to-moderate AD • MoA: PDE-4 Inhibitor • Administration: Applied to affected areas BID • Canadian Launch: June 2018

“EUCRISA™ (CRISABOROLE) NOW AVAILABLE IN CANADA.” Pfizer Canada, 7 Nov. 2018, www.pfizer.ca/eucrisa%E2%84%A2-crisaborole-now-available-canada.

D1T06.3D Ghoreschi Delgocitinib (LEOPharma)

• Indication: Atopic Dermatitis • Administration: Topical cream, 1, 3, 8, and 20 mg/g, with a treatment period of 8 weeks • MoA: JAK Inhibitor • Recruiting / Upcoming: • Phase 1: Topical cream, 1, 3, 8, and 20 mg/g, with a treatment period of 8 weeks

ClinicalTrials.gov

INCB018424 / Ruxolitinib (Incyte)

• Indication: Atopic Dermatitis • Administration: 1.5% or 0.75% BID • MoA: Selective JAK Inhibitor • Active: • Phase 1: A Pharmacokinetic Study in Pediatric Subjects • Phase 3: Efficacy and Safety Study in Adolescents and Adults • Other indications being investigated: COVID-19, ARDS, Leukemia, Myelofibrosis, Vitiligo, Atopic Dermatitis

ClinicalTrials.gov PF-07038124 (Pfizer)

• Indication: Atopic Dermatitis • Administration: 0.01% QD, 0.06% BID, 0.03% BID • MoA: PDE-4 • Completed • Phase 1: Safety, Tolerability, Skin Irritation Potential, And PK Following Topical Application Of PF-07038124 In Healthy Participants

ClinicalTrials.gov Psoriasis Targets Of Psoriasis Therapy

Etanercept

Ixekizumab

Ustekinumab

Guselkumab Adapted from Gooderham MJ, et al. J Eur Acad Dermatol Venereol 2018; 32(7):1111-9. The Evolution Of Systemic Therapy For Psoriasis

Conventional systemics: 2016 Pre-2000s Novel systemic: Acitretin Biologics: Anti-TNF Cyclosporine Anti-IL-12/23 2015 2018 Methotrexate Anti-IL-17 Secukinumab Brodalumab Anti-IL-23p19

2004 2006 2008 2010 2012 2014 2016 2018 2020

2019 2005 2008 Risankizumab Etanercept 2017 2006 Infliximab 2014 Apremilast 2018 2008 Certolizumab Adalimumab Will there be more? pegol … YES! Health Canada. Notice of Compliance database. https://health-products.canada.ca/noc-ac/index-eng.jsp Accessed April 4, 2019. Respective product monographs as of April 4, 2019 (full list in lecture notes) PASI Response, Short-Term

PASI 75 Week 10, 12 or 16 PASI 90 Week 10, 12 or 16 PASI 100 Week 10, 12 or 16

Etanercept 49% Etanercept 22% Etanercept 11% Infliximab 80% Infliximab 57% Infliximab N/A Adalimumab 73-80% Adalimumab 45-51.3% Adalimumab 20% Certolizumab 80.1% Certolizumab 52.2% Certolizumab 14.4% Ustekinumab 67-76% Ustekinumab 42-50% Ustekinumab 18% Secukinumab 77.1-81.6% Secukinumab 59% Secukinumab 30% Ixekizumab 87-89% Ixekizumab 70% Ixekizumab 40% Brodalumab 86.3% Brodalumab 86.3% Brodalumab 86.3% Guselkumab 86.3-91.2% Guselkumab 70-73.3% Guselkumab 34.1-37.4% Risankizumab 86.8-88.8% Risankizumab 73.2-75.3% Risankizumab 35.9-50.7% Adapted from: ETANERCEPT: Leonardi, C et al. N. Engl J Med 2003: 349:2014-22; Papp K et al Br J Dermatol 2005: 152:1304-1312: USTEKINUMAB PHOENIX 1. Leonardi C. Lancet 2008: 371: 1665-74; PHOENIX 2: Papp, K. Lancet 2008;371 :1675-87. SECUKINUMAB: Langley RG et al N Engl Med 2014;371:326-38. IXEKIZUMAB Gordon K et al NEJM 2016;345-356. RISANKIZUMAB: Gordon KB et al. Lancet Aug 2018 (SunPharma)

• Indication: Moderate-to-Severe PsO • Administration: subcutaneous injection 100 mg at Weeks 0, 4, and every twelve weeks thereafter • MoA: IL-23 Inhibitor • FDA Approval: March 2018 • Submitted to Health Canada February 2019 • NOC Status: submission currently under review

“Efficacy and Safety Study of SUNPG1623 - Full Text View.” Full Text View - ClinicalTrials.gov, Sun Pharma Global FZE, clinicaltrials.gov/ct2/show/NCT02980692? term=Tildrakizumab&cond=psoriasis&rank=4. PGA Responders in reSURFACE 1 and reSURFACE 2 PGA Responders in reSURFACE 1 PGA Responders in reSURFACE 2

PGA score of “clear” or “minimal” with at least a 2-grade reduction from baseline

PGA 0/1 Responders, ILUMYATM 100 mg PGA Responders Placebo PGA 0/1 Responders, ILUMYATM 100 mg PGA Responders Placebo Full Population (NRI), n=309 Full Population (NRI), n=307

100 100

80 PGA “clear” 80 PGA “clear” Placebo or Placebo or Responses “minimal” ( Responses “minimal” ( 60 %) 60 %) Week 4 3 Week 4 3 40 40 Week 12 7 Week 12 4 Patients, % 20 Patients, % 20

0 0

-20 -20 0 7 14 21 28 0 7 14 21 28 Weeks Weeks

Patients receiving ILUMYA™ 100-mg dose in reSURFACE 2 only; PASI 75 responders are defined as patients achieving ≥PASI 75 response at Week 28. PGA response is defined as a PGA score of “clear” or “minimal” with at least a 2-grade reduction from baseline. NRI=non-responder imputation; PGA=Physician’s Global Assessment. Reich K, et al. Lancet. 2017;390:276‒288; SUN Pharma, data on file. PASI Responders in reSURFACE 1 and reSURFACE 2 PASI Responders in reSURFACE 1 PASI Responders in reSURFACE 2

PASI 75 Responders, ILUMYATM 100 mg PASI 75 Responders, Placebo PASI 90 Responders, ILUMYATM 100 mg PASI 90 Responders, Placebo PASI 100 Responders, ILUMYATM 100 mg PASI 100 Responders, Placebo

100 Full Population (NRI), n=309 100 Full Population (NRI), n=309 Placebo PASI 75 Placebo PASI 75 Responses (%) Responses (%) 80 80 Week 4 1 Week 4 2 Week 12 6 60 60 Week 12 6

40 40

Patients, % 20 Patients, % 20

0 0

-20 -20 0 7 14 21 28 0 7 14 21 28 Weeks Weeks

Patients receiving ILUMYA™ 100-mg dose in reSURFACE 1 only; PASI 75 responders are defined as patients achieving ≥PASI 75 response at Week 28. PASI 75 response is defined as ≥75% improvement in PASI score from baseline; PASI 90 response is defined as ≥90% improvement in PASI score from baseline; PASI 100 response is defined as 100% improvement in PASI score from baseline. PASI 90 and PASI 100 outcome measures were included as secondary endpoints in the reSURFACE clinical development program. NRI=non-responder imputation; PASI=Psoriasis Area and Severity Index. Reich K, et al. Lancet. 2017;390:276‒288; SUN Pharma, data on file. Efficacy Profile Is Maintained in the Long-term Following 3 Years of Continuous Treatment: reSURFACE 1 and reSURFACE 2 Patients who completed the base studiesa and achieved PASI ≥50 were enrolled in an open-label extension study

PASI 75 Responders at Week 28 Onlyb (observed dataset), n=327 Part 3 Extension reSURFACE1 reSURFACE2 Part 3 Extension

100

80

60

40 PASI 75 Responders, ILUMYA™ 100 mg

Patients, % 20 PASI 90 Responders, ILUMYA™ 100 mg

0

-20 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 112 116 120 124 128 132 136 140 144 148 Week 9 out of 10 patients who achieved a PASI 75 response at 7 months still had clearer skin after 3 years of treatment with ILUMYA™ 100 mg

Patients receiving ILUMYA™ 100-mg dose in reSURFACE 1 and reSURFACE 2; no imputation of missing data was performed. aUp to 52/64 weeks of treatment in reSURFACE 1 and 2, respectively; bPASI 75 responders are defined as patients achieving ≥PASI 75 response at Week 28. PASI 75 response is defined as ≥75% improvement in PASI score from baseline; PASI 90 response is defined as ≥90% improvement in PASI score from baseline. PASI=Psoriasis Area and Severity Index. Thaçi D, et al. EADV 2018, Oral Presentation D3T01.1M. / LY3074828 (Eli Lilly)

• Indication: Plaque Psoriasis • Administration: Subcutaneous injection • MoA: IL-23A Inhibitor • Active / Recruiting: • Phase 3: Maintenance of Treatment Effect of LY3074828 in Participants With Moderate-to-Severe Plaque Psoriasis (OASIS-3) • Other indications being investigated: Ulcerative Colitis, Crohn’s Disease

ClinicalTrials.gov KX7 PASI 90 Response Weeks 16-52, NRI PASI 90 Inadequate Responders at Week 16 (AMAF) PBO/miri 300 mg SC Q8W (N=50) miri 30 mg SC Q8W/miri 300 mg SC Q8W (N=34) miri 100 mg SC Q8W/miri 300 mg SC Q8W (N=21) miri 300 mg SC Q8W/miri 300 mg SC Q8W (N=15)

100 82 84 77 80 67 76 60 65 60 40 40

Response Rate 20(%)

0 16 20 24 28 32 36 40 44 48 52 Weeks

Papp K, et al. Presented at: EADV 2018. Poster P1932.

External Use External KX8 PASI 100 Response Weeks 16-52, NRI PASI 90 Inadequate Responders at Week 16 (AMAF) PBO/miri 300 mg SC Q8W (N=50) miri 30 mg SC Q8W/miri 300 mg SC Q8W (N=34) miri 100 mg SC Q8W/miri 300 mg SC Q8W (N=21) miri 300 mg SC Q8W/miri 300 mg SC Q8W (N=15) 100

80 64 60 42 47 32 40

20 38 Response Rate 20(%) 33 14 0 16 20 24 28 32 36 40 44 48 52 Weeks

Papp K, et al. Presented at: EADV 2018. Poster P1932.

External Use External KX9 Most Common TEAEsa up to Week 52 PASI 90 Inadequate Responders at Week 16 (AMAF) miri 30 mg miri 100 mg miri 300 mg PBO/ Totalb SC Q8W/ SC Q8W/ SC Q8W/ miri 300 mg miri 300 mg miri 300 mg miri 300 mg miri 300 mg SC Q8W SC Q8W SC Q8W SC Q8W SC Q8W N=50 N=120 N=34 N=21 N=15 n (%) n (%) n (%) n (%) n (%) TEAEs Nasopharyngitis 9 (18) 8 (23) 4 (19) 4 (27) 25 (21) Upper respiratory tract infection 7 (14) 2 (5.9) 2 (9.5) 1 (6.7) 12 (10) Arthralgia 2 (4.0) 2 (5.9) 3 (14) 1 (6.7) 8 (6.7) Injection-site pain 3 (6.0) 2 (5.9) 2 (9.5) 0 7 (5.8) Urinary tract infection 2 (4.0) 1 (2.9) 1 (4.8) 2 (13) 6 (5.0) Back pain 0 3 (8.8) 3 (14) 0 6 (5.0) Headache 3 (6.0) 2 (5.9) 1 (4.8) 0 6 (5.0) Hypertension 3 (6.0) 2 (5.9) 0 1 (6.7) 6 (5.0) aAffecting ≥5% of total miri 300 mg SC Q8W arm. bIncludes all PASI 90 inadequate responders at Week 16 and all patients randomized to PBO at Week 0. Papp K, et al. Presented at: EADV 2018. Poster P1932.

External Use External (UCB)

• Indications: Moderate-to-Severe PsO • MoA: Dual IL-17A and IL-17F Inhibitor • Phase 3: A Study to Assess the Safety, Tolerability and Efficacy of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis (BE BRIGHT) • Other indications being investigated: AS, PsA, HS, RA • Launch: ? • Canadian Launch: ?

A Study to Assess the Safety, Tolerability and Efficacy of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis (BE BRIGHT). (2018). Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03598790? term=A+Study+to+Assess+the+Safety%2C+Tolerability+and+Efficacy+of+Bimekizumab+in+Adult+Subjects+With+Moderate+to+Severe+Chronic+Pl aque+Psoriasis+%28BE+BRIGHT%29&rank=1 (NCT03598790) BE VIVID PASI 90 and IGA 0/1 at Week 16 (ITT, NRI) Co-primary endpoints: superiority with bimekizumab versus placebo Key secondary endpoints: superiority with bimekizumab versus ustekinumab Week 16 PASI 90 Week 16 IGA 0/1

p<0.001 p<0.001 p<0.001 p<0.001 100 100 85 84.1

75 75

49.7 53.4 50 50

25 25

4.8 4.8 Proportion of patients achieving PASI 90 (%) Proportion of patients achieving PASI 0 0/1 (%) Proportion of patients achieving IGA 0 PlaceboPlacebo BimekizumabBKZ 320 320mg Q4Wmg Q4W Ustekinumab Placebo BimekizumabBKZ 320 mg 320 Q4W mg Q4W Ustekinumab (N=83)(N=83) (N=321)(N=321) (N=163) (N=83) (N=321)(N=321) (N=163)

p values for the comparison of treatment groups were based on the Cochran–Mantel–Haenszel test from the general association. Proportions were calculated using non-responder imputation (NRI). IGA 0/1: score of 0 (clear) or 1 (almost clear) with ≥2-category improvement relative to Baseline in Investigator's Global Assessment, scored on a 5-point scale; ITT: intent-to-treat; PASI 90: ≥90% improvement from Baseline in Psoriasis Area and Severity Index; Q4W: every four weeks. Bimekizumab is currently in clinical development. The safety and efficacy have not been established, and bimekizumab is not approved by any health authority worldwide. BE VIVID PASI 75 at Week 4 and PASI 100 at Week 16 (ITT, NRI) Secondary endpoints: PASI 75 response superiority with bimekizumab versus ustekinumab and placebo at Week 4, and PASI 100 response superiority with bimekizumab versus placebo at Week 16 Week 4 PASI 75 Week 16 PASI 100

p<0.001 p<0.001 p<0.001 p<0.001 100 100

76.9 75 75 58.6

50 50

25 25 20.9 15.3

2.4 0 Proportion of patients achieving PASI 75 (%) Proportion of patients achieving PASI

0 100 (%) Proportion of patients achieving PASI 0 PlaceboPlacebo BKZBimekizumab 320 mg Q4W 320 mg Ustekinumab PlaceboPlacebo BimekizumabBKZ 320 mg 320 Q4W mg Ustekinumab (n=83)(N=83) Q4W(N=321) (N=321) (N=163) (n=83)(N=83) Q4W(N=321) (N=321) (N=163)

For PASI 75 at Week 4 and PASI 100 at Week 16 (versus placebo only), the p value for the comparison of treatment groups was based on the Cochran–Mantel–Haenszel test from the general association; for PASI 100 at Week 16 (versus ustekinumab), the p value for a general association was based on a stratified Cochran–Mantel–Haenszel test where region and prior biologic exposure were used as stratification variables, is considered nominal, and was not controlled for multiplicity. Proportions were calculated using non-responder imputation (NRI). ITT: intent-to-treat; PASI 75/100: ≥75/100% improvement from Baseline in Psoriasis Area and Severity Index; Q4W: every four weeks.

Bimekizumab is currently in clinical development. The safety and efficacy have not been established, and bimekizumab is not approved by any health authority worldwide. Small Molecules

•Apremilast – PDE-4 Inhibitor •BMS-98165 - JAK/TYK Inhibitor •PF-06700841 (Brepocitinib) - •PF-06826647 - TYK-2 Inhibitor •Tofacitinib approval for PsA

ClinicalTrials.gov BMS-986165 (Bristol-Myers Squibb)

• Indication: Plaque Psoriasis • Administration: Topical gel applied once daily on affected areas for 12 weeks • MoA: TYK-2 Selective Inhibitor • Recruiting / Active: • Phase 3: Long-Term Safety and Efficacy • Phase 3: An Investigational Study to Evaluate BMS-986165 v Placebo • Other indications being investigated: UC, Lupus, PsA

ClinicalTrials.gov BMS-986165 (Bristol-Myers Squibb) • BMS-986165 binds to a regulatory domain unique to TYK-2, preventing TYK-2 activation and inhibiting downstream signaling, which are integral to several immune-related diseases1,2

BMS-986165 ATP-binding active site

Compared with JAK-1/JAK-3 inhibition of the active domain, BMS-986165 is approximately 200-fold more selective in cell-based assays1

Regulatory domain Active domain (pseudokinase domain)

ATP, adenosine triphosphate; JAK, Janus kinase; TYK, tyrosine kinase. 1. Included with permission from Gillooly K, et al. ACR 2016; Poster 11L. 2. Adapted from Tokarski JS, et al. J Biol Chem 2015;290:11061–11074. 3. Included with permission from Catlett IM, et al. EULAR 2017; Poster SAT0226. PF-06700841 / Brepocitinib (Pfizer)

• Indication: plaque psoriasis • Administration: Topical / Oral • Topical – 0.1%, 0.3%, 1.0% QD / BID • Oral – 4 week induction of 60 mg 0D, followed by 10 mg OD, 30 mg OD, 100 mg QW • MoA: TKY2/JAK1 • Completed: • Phase 2: Study To Evaluate Safety And Efficacy Of PF-06700841 In Subjects With Moderate To Severe Plaque Psoriasis • Other indications being investigated: SLE, Crohn’s, PsO, PsA, UC, AA

ClinicalTrials.gov PF-06826647 / C2501004 (Pfizer)

• Indication: Plaque Psoriasis • Oral dose, daily for 16 weeks with 24-week open label extension • MoA: TYK-2 Selective Inhibitor • Active: • Phase 2: A Study to Evaluate PF-06826647 for Treatment of Moderate-to-Severe Plaque Psoriasis • Other indications being investigated: HS, UC

ClinicalTrials.gov Tofactinib (Pfizer)

MoA: Inhibits JAK-1, -2, -3 & TYK-2 (lesser extent) Approved in PsA 5 mg PO BID Not approved for PsO Topicals

• Tapinarof Cream 1% (Dermavant) • Brepocitinib / PF-06700841 (Pfizer) • Halobetasol Propionate and Tazarotene (Bausch Health)

ClinicalTrials.gov Tapinarof Cream 1% / DMVT-505 (Dermavant)

• Indication: Plaque Psoriasis • Administration: Topical cream QD on affected areas for 12 weeks • MoA: AhR-Modulating Agent (non-steroid) • Active: • Phase 3: Long Term Extension Study

ClinicalTrials.gov Tapinarof: Therapeutic AhR Modulating Agent

(TAMA) Proposed MOA of Tapinarof1,2 • Tapinarof is a topical, small molecule TAMA that crosses the cell membrane and directly TAP Tapinarof binds to and activates AhR transcription 1 factor TAP

AhR Cytoplasm • Activated Tapinarof-AhR complex moves

into the nucleus and binds ARNT, which TAP AhR TAP facilitates the transformation of the complex AhR into its high-affinity DNA binding form1 ARNT • Activated Tapinarof-AhR-ARNT complex TAP Gene Expression interacts with DNA and modulates gene AhR expression1 ARNT

Nucleus

AhR, aryl hydrocarbon receptor; ARNT, aryl hydrocarbon receptor nuclear translocator; MOA, mechanism of action; TAMA, therapeutic aryl hydrocarbon receptor modulating agent; Th, T helper cell. 1. Smith SH et al. J Inv Dermatol 2017;137:2110–2119. 2. Furue M et al. J Dermatological Sci. 2015;80:83–88. Tapinarof Phase 3 PSOARING Program – PGA Response* Primary Endpoint Achieved PGA Score of 0 or 1 and ≥2-grade Improvement from Baseline at • Tapinarof demonstrated superior PGA Week 12 (ITT, MI) response rates at Week 12 as evidenced %60 by highly statistically significant Δ 29.4% Δ 33.9%

difference vs vehicle (P<0.0001 and %50 P<0.0001)† P<0.0001 P<0.0001 40.2% %40 • 35.4% and 40.2% of patients achieved 35.4%

treatment success at Week 12 with %30

tapinarof 1% cream QD vs 6.0% and % (SEM) 6.3% for vehicle %20 MEAN TREATMENT SUCCESS, TREATMENT MEAN

%10 • Replicable and consistent results 6.0% 6.3% observed across both studies %0 Tapinarof 1% QD Vehicle QD Tapinarof 1% QD Vehicle QD (n=340) (n=170) (n=343) (n=172)

PSOARING 1 PSOARING 2

*PGA score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline. †P-value based upon Cochran-Mantel-Haenszel analysis stratified by baseline PGA score. ITT, intention-to-treat; MI, multiple imputation; PGA, Physician Global Assessment; QD, once daily; SEM, standard error of mean. Dermavant DOF [DMVT-505-3001 PGA Response Table 14.2.1.1.1; Aug 2020]; Dermavant DOF [DMVT-505-3002 PGA Response Table 14.2.1.1.1; Aug 2020]. Tapinarof Phase 3 PSOARING Program – PASI75* Key Secondary Endpoint Achieved

PASI75 from Baseline at Week 12 • PASI75 at Week 12 was statistically (ITT, MI) significantly higher in both tapinarof %60 Δ 40.7% groups compared with vehicle groups Δ 25.9% (P<0.0001 and P<0.0001)† P<0.0001 %50 P<0.0001 %47.6 • 36.1% and 47.6% of patients achieved %40 PASI75 at Week 12 with tapinarof 1% 36.1%

cream QD vs 10.2% and 6.9% for vehicle %30 % (SEM)

%20

MEAN PASI75 RESPONSE RATE, RESPONSE RATE, MEAN PASI75 %10.2 %10 %6.9

%0 Tapinarof 1% QD Vehicle QD Tapinarof 1% QD Vehicle QD (n=340) (n=170) (n=343) (n=172)

PSOARING 1 PSOARING 2

*PASI75 response: ≥75% improvement in PASI from baseline. †P-value based upon Cochran-Mantel-Haenszel analysis stratified by baseline PGA score. PGA response: PGA score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline. ITT, intention-to-treat; MI, multiple imputation; PASI, Psoriasis Area and Severity Index; QD, once daily; SEM, standard error of mean. Dermavant DOF [DMVT-505-3001 PASI75 Table 14.2.2.1.1; Aug 2020]; Dermavant DOF [DMVT-505-3002 PASI75 Table 14.2.2.1.1; Aug 2020]. Brepocitinib / PF-06700841 (Pfizer)

• Indication: plaque psoriasis • Administration: Topical / Oral • Topical – 0.1%, 0.3%, 1.0% QD / BID • Oral – 4 week induction of 60 mg 0D, followed by 10 mg OD, 30 mg OD, 100 mg QW • MoA: TKY2/JAK1 • Recruiting / Active: • Phase 2: Dose Ranging Study To Assess Efficacy, Safety and Tolerability Of PF-06700841 Topical Cream In Psoriasis • Completed: • Phase 2: Study To Evaluate Safety And Efficacy Of PF-06700841 In Subjects With Moderate To Severe Plaque Psoriasis • Other indications being investigated: SLE, Crohn’s, PsO, PsA, UC, AA

ClinicalTrials.gov Halobetasol Propionate and Tazarotene (Bausch Health)

• MoA: Selectively binds RARβ > RARγ > RARα • FDA Approval: April 2019 • NOC: June 2020

Valeant Pharmaceuticals International, Inc. “FDA Issues Complete Response Letter For DUOBRII™ (Halobetasol Propionate and Tazarotene) Lotion.” PR Newswire: News Distribution, Targeting and Monitoring, 18 June 2018, www.prnewswire.com/news-releases/fda-issues-complete-response-letter-for-duobrii-halobetasol-propionate-and-tazarotene-lotion-300667565.html. Health, Bausch. “Health Canada Issues Notice of Compliance for Bausch Health's DUOBRII™.” Cision in Canada, 11 June 2020, www.newswire.ca/news-releases/health-canada-issues-notice-of- compliance-for-bausch-health-s-duobrii-tm--814212546.html. Primary Endpoint: treatment success* achieved at week 8 2-Grade IGA Improvement From Baseline and “Clear” or “Almost Clear” Study 3011 Study 3022

50 50 45 p<0.001 p<0.001

38 36 38

25 25

13 13 13 7 Primary endpoint achieved (%) Primary endpoint achieved (%)

0 0 Visit Week 8 Visit Week 8 HP 0.01%/TAZ 0.045% Lotion (n=135) HP 0.01%/TAZ 0.045% Lotion (n=141) Vehicle (n=68) Vehicle (n=74)

1. Percentage of patients completing Study 301: HP 0.01%/TAZ 0.045% Lotion 83% , Vehicle 83.8% 2. Percentage of patients completing Study 302: HP 0.01%/TAZ 0.045% Lotion 85.1%, Vehicle 82.4% HP, halobetasol propionate; TAZ, tazarotene; IGA, investigator’s global assessment of disease severity 76 *Treatment success defined as at least a 2-grade IGA improvement from baseline and “clear” or “almost clear.” Stein Gold L, et al. J Am Acad Dermatol. 2018;79(2):287-293. Week 8 Treatment Success

Baseline Week 2 Week 8

Actual clinical results. Photos have not been retouched. Individual results may vary. Images on file. 77 Treatment Success Over Time

4 weeks post-treatment

Baseline Week 2 Week 8 Week 12

Actual clinical results. Photos have not been retouched. Individual results may vary. Images on file. 78 Palmoplantar pustulosis ANB019 / ANB019-003 (AnaptysBio)

• Indication: Palmoplantar Pustulosis • Administration: Subcutaneous injection with a treatment period up to 12 weeks • MoA: IL-36 Inhibitor • Recruiting: • Phase 2: Efficacy and Safety of ANB019 in Subjects With Palmoplantar Pustulosis (PPP) • Other indications being investigated: Generalized Pustular Psoriasis

ClinicalTrials.gov Hidradenitis Suppurativa Hidradenitis Suppurativa

As of November 5th 2019, there As of October 31st 2020, there were: were: 32 active HS trials 53 active HS trials listed on clinicaltrials.gov listed on clinicaltrials.gov There are 84 trials listed total There are 109 listed total

ClinicalTrials.gov Hidradenitis Suppurativa

Products being investigated:

• BAY 1830839 (Bayer) – IRAK4 • PF-06700841 (Pfizer) – TYK2 • Bimekizumab (UCB): IL-17 • PF-06826647 (Pfizer) – TYK2 • Brodalumab (Bausch Health): IL-17 • Risankizumab (BI) – IL23 • Cannabis oil • Ruxolitinib 1.5% Cream – • CFZ533 (Novartis) – CD40 JAK1/2 • LY3041658 (Eli Lilly) • Secukinumab (Novartis) – IL17A • LYS006 (Eli Lilly) • Upadacitinib (AbbVie) – JAK1 • PF-06650833 (Pfizer)– IRAK4

ClinicalTrials.gov INCB54707-203 (Ruxolitinib)

• Indication: HS • MoA: JAK Inhibitor • Not Yet Recruiting: • Phase 2: topical ruxolitinib 1.5% for HS • Other indications being investigated: COVID-19, ARDS, Leukemia, Myelofibrosis, Vitiligo, Atopic Dermatitis

ClinicalTrials.gov Hand Dermatitis ARQ-252 (Arcutis)

• Indication: Chronic Hand Dermatitis • Administration: 0.1%, 0.3% topical cream QD, BID • MoA: JAK1 Inhibitor • Active: • Phase 1: Safety and Efficacy of ARQ-252 Cream in Subjects With Chronic Hand Eczema

ClinicalTrials.gov Delgocitinib (LEOPharma)

• Indication: Chronic Hand Dermatitis • Administration: Topical cream • MoA: JAK Inhibitor • Completed: • Phase 2b: Dose-ranging Trial to Evaluate Delgocitinib Cream 1, 3, 8, and 20 mg/g Compared to Delgocitinib Cream Vehicle Over a 16-week Treatment Period in Adult Subjects With Chronic Hand Eczema

ClinicalTrials.gov

Acne Trifarotene Cream 0.005% w/w (50mcg/g) (Galderma) • Indication: acne vulgaris of the face and/or trunk (≥12 y/o) • MoA: Specifically targets RAR-γ • Administration: Apply thin layer to affected areas of face and/ or trunk once a day, in the evening. • One pump for the face and two pumps to cover the back, shoulders and chest. • An additional pump to cover the middle or lower back if needed. • Pack size: 75 g pump trade size, 2 g tube sample • Health Canada NOC: November 2019

ClinicalTrials.gov Tretinoin 0.05% and Benzoyl peroxide 2.5% (Bausch Health)

• Indication: Acne Vulgaris • MoA: Vitamin A metabolite with antimicrobial properties • Completed: • Phase 3: A Study to Evaluate IDP-120 Gel for Treatment of Acne Vulgaris • Administration: Topical gel applied QD on affected areas for 12 weeks • Other indications being investigated: None

ClinicalTrials.gov IDP 126 (Bausch)

• Indication: Moderate-to-Severe Acne • Administration: topical gel applied once daily for 12 weeks • Active Ingredients: Clindamycin and Adapalene • Recruiting / Active: • Phase 3: Efficacy and Safety of IDP-126 Gel

ClinicalTrials.gov 0.045% Tazarotene Lotion

• Indication: Acne vulgaris > 9 y/o • Administration: apply to the affected areas once daily • MoA: RARβ / RARγ • FDA Approval: December 2019 • Health Canada NOC: ? 2021

COMING SOON

ClinicalTrials.gov Clascoterone (Cassiopea)

• Indication: acne vulgaris > 12 y/o • Administration: apply thin layer (approximately 1 g) to affected area twice daily • MoA: Androgen receptor inhibitor • FDA Approval: August 2020 • NOC: ? 2021 • Other indications being investigated: androgenic alopecia COMING SOON

ClinicalTrials.gov Skin Cancer Methyl Aminolevulinate (Galderma)

• Indications: AKs, BCC, SCC in situ • MoA: Light activation of accumulated porphyrins leads to a photochemical reaction and thereby phototoxicity to the light-exposed target cells • Dosing: For treatment of actinic keratoses (AK), one session of photodynamic therapy (PDT) should be administered with either red LED light via a suitable lamp (c-PDT) or exposure to natural daylight (DL-PDT).

Metvix Product Monograph 2017 Sonidegib (SunPharma)

• Background: locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC) • MoA: hedgehog pathway inhibitor (HPI) - approved in laBCC • NOC: Submitted June 2020

COMING SOON

JEADV2018:32;372-381 Melanoma

Products under investigation: • Dabrafenib - BRAF Enzyme Inhibitor • Vemurafenib - BRAF Enzyme Inhibitor • Cobimetinib – MEK-1/MEK-2 Inhibitor • Trametinib – MEK-1/MEK-2 Inhibitor • LY3022855 - CSF-1R Inhibitor

ClinicalTrials.gov Vitiligo INCB018424 / Ruxolitinib (Incyte) • Indication: Vitiligo • Administration: Topical • MoA: Selective JAK inhibitor • Recruiting / Active: • Phase 2: A Study of INCB018424 Phosphate Cream in Subjects With Vitiligo • Phase 3: Long Term Efficacy and Safety • Phase 3: Topical Ruxolitinib Evaluation in Vitiligo • Phase 3: Topical Ruxolitinib Evaluation in Vitiligo Study • Other indications being investigated: COVID-19, ARDS, Leukemia, Myelofibrosis, Vitiligo, Atopic Dermatitis

ClinicalTrials.gov Rothstein, Brooke, et al. “Treatment of Vitiligo with the Topical Janus Kinase Inhibitor Ruxolitinib.” Journal of the American Academy of Dermatology, vol. 76, no. 6, 2017, doi:10.1016/j.jaad.2017.02.049. INCB18424 / Ruxolitinib (Incyte)

Conclusions • At week 24 Ruxolitinib monotherapy has produced significant facial and total body repigmentation of vitiligo lesions • Continued improvement seen through 52 weeks of treatment (highest responses with 1.5%) • Well tolerated, no serious AEs reported

Rothstein, Brooke, et al. “Treatment of Vitiligo with the Topical Janus Kinase Inhibitor Ruxolitinib.” Journal of the American Academy of Dermatology, vol. 76, no. 6, 2017, doi:10.1016/j.jaad.2017.02.049. Cerdulatinib Gel / DMVT 502 (Dermavant)

• Indication: Segmented Vitiligo • MoA: JAK Inhibitor • Recruiting / Active: • Phase 2: Safety and Tolerability Study of Cerdulatinib Gel, 0.37% in Adults With Vitiligo • Administration: topical, 0.37% cerdulatinib gel BID for 6 weeks • Other indications being investigated: peripheral t-cell lymphoma

ClinicalTrials.gov PF-06651600 & PF-06700841 (Pfizer)

• Indication: Active, Non-Segmental Vitiligo • Administration: tablet PO QD • MoA: JAK-3, TYK-2 Inhibitor • Recruiting / Active: • Phase 2: A Phase 2b Study To Evaluate The Efficacy And Safety Profile Of PF-06651600 And PF-06700841 • Other indications being investigated: Alopecia, Crohn’s, Ulcerative Collitis, RA

ClinicalTrials.gov Alopecia Alopecia Totalis / Universalis

• Incidence of 0.1-0.2% • Lifetime risk of 1.7%-2% • Chronic condition • Comorbidities: anxiety, depression, other autoimmune conditions Currently no approved treatment options

Fricke M. Epidemiology and Burden of alopecia areata: a systemic review. Clinical, Cosmetic and Investigational Dermatology. 2015; Vol 8. 397-403. CTP-543 / Ruxolitinib (Concert)

• Indication: Moderate-to-Severe Alopecia Areata • Administration: 8mg, 12 mg, • MoA: JAK Inhibitor • Active / Recruiting: • Phase 2: Extension Study to Evaluate Safety and Efficacy • Phase 3: Efficacy and Safety • Other indications being investigated: COVID-19, ARDS, Leukemia, Myelofibrosis, Vitiligo, Atopic Dermatitis

ClinicalTrials.gov CTP-543 / Ruxolitinib (CoNCERT) 12mg BID

“CTP-543.” Concert Pharmaceuticals, www.concertpharma.com/product-pipeline/ctp-543/. CTP-543 / Ruxolitinib (concert) – 12mg BID

“CTP-543.” Concert Pharmaceuticals, www.concertpharma.com/product-pipeline/ctp-543/. Patient SALT improvement thresholds

“CTP-543.” Concert Pharmaceuticals, www.concertpharma.com/product-pipeline/ctp-543/. Responders ≥ 50% Change in SALT relative to baseline

“CTP-543.” Concert Pharmaceuticals, www.concertpharma.com/product-pipeline/ctp-543/. Itch Prurigo Nodularis

• Prurigo Nodularis (PN) • Chronic prurigo subtype • Difficult to treat • High disease burden • Regulation of IL-31 mRNA in lesions up to 50 times of healthy skin

Zeidler C et al. Acta Derm Venerol 2018; 98: 173-9 Sonkoly E et al. JACI 2006; 117: 411-7 Nemolizumab / CD14152 (Galderma)

• Indication: Prurigo Nodularis • Administration: 30 mg or 60 mg subcutaneous • MoA: IL-31 Receptor A Inhibitor • Active / Recruiting: • Phase 3: Efficacy and Safety • Phase 3: Long-term Study • Other indications being investigated: AD

ClinicalTrials.gov IL-4 and IL-13 Antagonism

Chronic pruritis is possibly mediated via the shared receptor subunit for IL-4 and IL-13 on sensory neurons and the JAK signaling pathway

…for prurigo nodularis

Paller, Amy S., et al. “Therapeutic Pipeline for Atopic Dermatitis: End of the Drought?” Journal of Allergy and Clinical Immunology, vol. 140, no. 3, 2017, pp. 633–643., doi:10.1016/j.jaci.2017.07.006. Difelikefalin

• Indication: Notalgia Paresthetica • Administration: oral tablet BID • MoA: KOR Agonist • Upcoming: • Phase 2: Efficacy and Safety for Moderate-to-Severe Pruritis for adults with Notalgia Paresthetica • Other Indications Being Investigated: Cholestatic Pruritis Urticaria Bilastine (Aralez) Bilastine

• Indication: Chronic Spontaneous Urticaria > 12 y/o • Administration: Oral 20 mg • MoA: highly selective H1 inhibitor • Other Indications: seasonal allergic rhinitis

ClinicalTrials.gov Rupatadine

• Indication: Chronic Spontaneous Urticaria > 2 y/o • Administration: 10 mg tablet or 1mg/mL solution • MoA: highly selective H1 inhibitor, PAF inhibitor • Other Indications: allergic rhinitis, CSU

ClinicalTrials.gov Rupatadine has Fast Onset of Action in Urticaria

Mean Pruritus Score was significantly reduced by rupatadine Mean number of wheals was significantly reduced by rupatadine at 12 and 24 hours at 12 and 24 hours

* p < 0.01 pruritus score reduction from baseline after 12 h with 10 mg ruptadine * p < 0.01 , ** p < 0.005 **p < 0.001 pruritus score reduction from baseline after 12 h with 20 mg ruptadine Wheal reduction from baseline after 12/24 h treatment with 10 and 20 mg rupatadine † p < 0.01 and p<0.001 vs placebo after 24 h drug intake with 10 and 20 mg rupatadine, respectively

Gimenez-Arnau A, et al. Allergy. 2007;62(Suppl.83):306. / QGE031 (Novartis)

• Indication: Chronic Spontaneous Urticaria • Administration: 72 mg/mL followed by 120 mg/mL PFS or 120 mg/mL followed by 120 mg/mL PFS • MoA: IgE/FcεRI • Active / Recruiting: • Phase 1: Study of Mechanism of Action of Ligelizumab (QGE031) in Patients With Chronic Urticaria (MASTER) • Phase 3: Efficacy and Safety of Ligelizumab, Patients Who Completed a Previous Study With Ligelizumab • Phase 3: Efficacy and Safety in Adolescents and Adults Inadequately Controlled With H1-antihistamines

ClinicalTrials.gov (GSK)

• Indication: Chronic Spontaneous Urticaria • Administration: 100mg SQ injections administered at two different anatomical sites at week zero, 2,4,6, and 8 for a total of 5 doses • MoA: IL-5 • Active / Recruiting: • Phase 1: Treatment of Chronic Spontaneous Urticaria • Approved In: severe eosinophilic asthma • Other Indications Under Investigation: COPD, Eosinophilic Chronic Rhinosinusitis, Churg-Strauss Syndrome

ClinicalTrials.gov LY3454738 (Eli Lilly)

• Indication: Chronic Spontaneous Urticaria • Administration: IV • MoA: CD200R monoclonal antibody agonist • Active / Recruiting: • Phase 2: A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria • Other Indications Under Investigation: AD

ClinicalTrials.gov Remibrutinib / LOU064 (Novartis)

• Indication: Chronic Spontaneous Urticaria • Administration: oral • MoA: BTK Inhibitor • Active / Recruiting: • Phase 2: Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1- antihistamines • Other Indications Under Investigation: Sjogren Syndrome, Atopic Diathesis, Atopic Dermatitis

ClinicalTrials.gov Anesthetics Lidocaine & Tetracaine 7%/7% (Crescita)

• Indication: local anesthetic for superficial dermatologic and cosmetic procedures • Administration: topical cream • Active Ingredients: Lidocaine & Tetracaine (7%/7%)

ClinicalTrials.gov Lidocaine & Tetracaine 7%/7% (Crescita)

• Fast-acting topical local anesthetic preparation • 20-to-30-minute application for minor dermatological procedures • 60-minute application for major dermatological procedures • Anesthetic effect is reliable, long-lasting (>9 hours) • Works well on the face as well as other parts of the body • Efficacy in a wide range of dermatological procedures • Pliaglis is a cold chain product with 2-year shelf life1

1In some jurisdictions label allows product to be stored at room temperature for up to 3 months

127 Lidocaine & Tetracaine 7%/7% Case Study: Laser Resurfacing Pain Scores 9 Mean Pain Score p<0.001 7 EMLA Pliaglis 5.25 2.66 5

Adequate Pain Relief p<0.001

No. Patients 2 EMLA Pliaglis 0 20% 95% 1 2 3 4 5 6 7

Pain Score Drugs were well tolerated EMLA with no serious adverse Alster TS, Lupton JR. Evaluation of a novelPliaglis topical anesthetic agent for cutaneous sequelae laser resurfacing: a randomized comparison study. Dermatol Surg. 2002;28:1004-1006. 128 Questions? Thank you for listening

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